PMID- 8190495 TI - [Portrait of Albert Schweitzer at the eponymous hospital in Hatvan]. PMID- 8190496 TI - [Technics and results of pancreas transplantation]. AB - Long-term normoglycaemia cannot be achieved in patients with insulin dependent diabetes mellitus neither with conventional nor with intensified insulin therapy. The only ideal method to obtain this seems the islet cell or pancreas transplantation. The number of pancreas transplantation approaches 5000 all over the world. The first simultaneous pancreas-kidney transplantation in Germany was performed in 1979 by the Munich group. Till 1991 in Grosshadern 141 pancreas transplantations have been performed. At the beginning duct occlusion (n = 106) later bladder drainage (n = 35) were used as a standard procedure. The authors discuss in detail the indications and contraindications, the types of pancreas transplantation, the different diversions of exocrine secretion. They analyse the effect of pancreas transplantation upon diabetic metabolism, retinopathy, neuropathy, nephropathy and quality of life, based on own experiences and literary data. At present the indication for pancreas transplantation is the stadium of late complications in IDDM. Because of the definitive lesions its beneficial effect is limited. After successful transplantation the peripheral (and autonomic?) neuropathy improves, the retinopathy seems to remain stabile, and the pancreas protects the transplanted kidney against recurrent diabetic nephropathy. Most patients will become insulin independent with tight metabolic control, but the complications of immunosuppressive therapy must be taken into consideration. The working ability and the quality of life seem to improve considerably. PMID- 8190497 TI - [Management of secondary pneumothorax]. AB - Results on treatment of 445 episodes of 420 patients suffering from spontaneous pneumothorax (sptx) are reported. The overall mortality was 1.4%. No death was encountered during the treatment of 246 primary sptx patients. Mortality of secondary ptx was 3.4%. Detailed data of the recent 92 patients are analysed. Recurrence rate of drainage (ICC) therapy of primary sptx was 8/33. Five out of eight patients were operated on. 16 thoracotomies were performed altogether in this group of patients. 3/18 patients were lost in the ICC treatment only subgroup of secondary sptx panel. 1/25 patient died in the ICC+pleurodesis subgroup of secondary sptx patients. Drainage and subsequent thoracotomy in case of failure of ICC treatment or of numerous recurrences is the choice to follow in primary sptx cases. Apart from exceptions there is no room for chemical pleurodesis in this form of ptx. On the other hand the ICC drainage with pleurodesis offers the best chances in the treatment of secondary sptx. Tetracycline and Vibramycin were proven as the best pleurodesis materials in first instances. Tissucol is recommended to use in case of failure of previous pleurodesis attempts. PMID- 8190498 TI - [Management of calculi in the middle and lower section of the ureter using an ureterorenoscope]. AB - Ureterorenoscope (URS) is one of those achievements which can be successfully used in the treatment of ureter stones these days. Authors report on their experience obtained in URS treatment for several years and discuss its indication. They apply the procedure primarily when stones are blocked in the middle or lower part of the system as well as secondary adjuvant treatment after extracorporeal shock wave lithotripsy or percutaneous litholapaxy. PMID- 8190499 TI - [Non-immune hydrops fetalis successfully treated by intrauterine transfusion]. AB - One severe non immune hydrops fetalis was treated by intrauterine intravascular red cell transfusion on the 29th gestational week. The fetus was born vaginally in excellent condition on the 37th week of gestation. PMID- 8190500 TI - [Erythrocyte deformation in acute necrotizing pancreatitis]. PMID- 8190501 TI - [Clinical and sonographic meniscus diagnosis]. AB - Clinical examination still plays an important role in diagnosing meniscal tears. The types of sensitive nerves in the knee joint are responsible for nonspecific pain, which is often correlated with too little specificity in meniscal tests. Ultrasound examination of meniscal structures of the knee joint has been debated extensively in recent years. Criticism of this noninvasive technique was due to small patient groups, improper technical and inaccurate manual standards. Since 1988 ultrasound of the tibial meniscus has become a standard technique in our Department of Orthopaedic Surgery with defined criteria of the intersecting plane and evaluation of ultrasound images. A prospective follow-up study during 6/1988 and 5/1993 including 1186 ultrasound examinations before arthroscopy, was performed. The sensitivity for ultrasound of the lateral meniscus was 58% and for the medial meniscus 83%. Specificity with 98% for the lateral and 90% for the medial meniscus was good. Sonographic detection of meniscal tears depends on the shape and location of meniscal tears. This has been shown by experimental studies in cadavers. A follow-up study including 113 knee joints was performed to prove the value of clinical and ultrasound examination in relation to arthroscopy. The sensitivity of sonography for medial meniscus was 81% and 40% for the lateral meniscus. Although the sensitivity of the clinical examination was 81% (medial) and 47% (lateral), the low specificity of 70% for meniscus tears indicated that it was because of false-positive clinical evaluation of meniscal disorders. In young patients with reflectory muscle spasm and those with acute trauma of the knee joint, clinical examination of the meniscal structures showed poor results. In these cases, too, ultrasound examination showed advantages. Ultrasound of the knee joint meniscus is noninvasive, reproducible and low cost. In cases of uncertain clinical results, ultrasound offers a good opportunity to visualize meniscal disorders. PMID- 8190502 TI - [Proton spin tomography in meniscus diagnosis]. AB - Magnetic resonance imaging (MRI) is an excellent method of examining the meniscus with an accuracy of about 91-94% for the median meniscus and 88.4-100% for the lateral meniscus in T1-weighted images. The precision of the diagnosis can be increased to 100% by the use of paramagnetic contrast medium (gadolinium DTPA), as was shown by the evaluation of 170 knee joints. The reason it is difficult to evaluate the meniscus without contrast medium is a residual meniscus or regenerated meniscus. We are therefore dramatically able to reduce the number of diagnostic arthroscopies for evaluation of the meniscus. PMID- 8190503 TI - [Relevance of proton spin tomographic meniscus diagnosis in correlation with arthroscopy]. AB - Arthroscopy of the menisci is considered the gold standard by which all noninvasive imaging procedures of the knee are measured. In a prospective study we evaluated the use of MRI in 50 patients in whom a disorder of the meniscus was suspected clinically; this was followed by an arthroscopic examination by an experienced arthroscopist. The MR studies were performed after clinical evaluation and were interpreted by an experienced radiologist, who had no knowledge of the clinical findings. The accuracy of the diagnosis from MRI was 78% for the medial meniscus (sensitivity 79% and specificity 78%) and 94% for the lateral meniscus (sensitivity 50% and specificity 98%). The average age of the patients was 34 years, with a range of 3-73 years. The imaging studies revealed 9 false-positive tests and suggested that the meniscus was either degenerated or torn in the horizontal plane. In all 9 menisci the abnormal MR imaging signal was limited to the posterior horns. The positive predictive value was 59% and the negative predictive value was 94%, representing a moderate level of diagnostic certainty both in patients who had a positive result and in those who had a negative result. The high predictive negative value of MRI indicates that a negative MRI is quite reliable for meniscal lesions. The problem areas in MR imaging are the popliteal tendon sheath and the transverse ligament. This ligament is seen in association with a large branch of the lateral inferior geniculate artery and may be mistaken for a grade 3 signal intensity in the anterior horn of the lateral meniscus. PMID- 8190504 TI - [Arthroscopic partial double meniscectomy]. AB - Arthroscopic treatment of meniscal pathology has become a routine procedure within the last 10 years. In our patients who underwent arthroscopic surgery for multiple reasons we found 226 cases with combined lesions of the medial and lateral menisci. Eliminating the patients with instabilities, chondral lesions grade IV and general diseases like rheumatoid arthritis and those who had had surgery previously, 71 patients were left. Forty-four (62%) were male and 27 (38%) female. The average age was 52 years. The lesion was located in the right knee in 41 cases (58%) and in 31 cases (42%) in the left one. The duration of symptoms was more than 3 months in most cases. Eleven patients (15%) had a trauma in their history. A standardized interview according to the Tapper and Hoover score was carried out in each patient. Out of the 77 patients with partial double meniscectomy we were able to examine 55 patients. According to the Tapper and Hoover score the following results were evaluated: 17 patients (31%) rated excellent. In 28 cases (51%) the result was good. 8 patients (15%) showed fair results. The main cause in this group was a slight feeling of instability and a mild loss of function (lack of flexion < 5 degrees, lack of extension < 10 degrees). Two patients (3.6%) were rated poor. Of the patients 89% were satisfied with this surgical procedure and would choose it again. Only 11% (n = 6) were not satisfied with the outcome of the procedure and would prefer arthrotomy. Our follow-up study indicates that arthroscopic double partial meniscectomy gives good results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190505 TI - [Meniscus resection versus reattachment of the meniscus]. AB - Stable partial-thickness tears, longitudinal tears of less than 5 mm length and short (5 mm or less) radial tears can sometimes be left alone. Tears known to be definitely repairable are traumatic longitudinal tears within the vascular zone of the meniscus with minimal damage to the meniscus body fragment. When an attempt is to be made to repair tears in the avascular zone, it is necessary to utilize healing-enhancement techniques such as synovial fringe rasping and fibrin clot insertion. The survival rate for repaired menisci at a minimum follow-up time of 10 years was 79% in the author's cases. Intermediate (5 year) results after partial meniscectomy show a diminished incidence of post-surgical degenerative changes when compared to total meniscectomy. PMID- 8190506 TI - [Reattachment of the meniscus. Techniques, long-term results and recommendation for individual treatment]. AB - To prevent the joint degeneration which commonly occurs after meniscectomy, meniscal repair has become the treatment of choice. With more advanced arthroscopic techniques, including application of fibrin clot and synovial flaps, almost all types of meniscal ruptures are technically accessible and have been found to heal. However, from a biomechanical point of view only a meniscus with a peripheral longitudinal rupture functions as a normal meniscus after repair and, therefore, minimizes cartilage degeneration; this statement was confirmed by long term follow-up evaluations. In this respect, the biomechanical value of healed intra-substance ruptures is more doubtful; long-term follow-up evaluations are not yet available. The different arthroscopic repair techniques seem to be safe if used properly and are followed by healing rates similar to after open techniques. No technique has been shown to be superior to another, but they are sometimes more effective if combined. PMID- 8190507 TI - [Arthroscopic reattachment of the meniscus]. AB - This article defines the indications for arthroscopic meniscus repair. The inside out technique is described with special emphasis on healing enhancement by the use of an exogenous fibrin clot. PMID- 8190508 TI - [Viable meniscus transplantation]. AB - The integrity of the semilunar cartilages has proved to be the best safeguard against mechanical degenerative changes. One can postulate that restoring normal congruency between the femur and tibia with intact menisci would be the ideal solution to many mechanical knee problems. Several semilunar cartilages have been transplanted with good functional results in medial and lateral compartmental meniscal disease. However, this form of chondroprotection in the load-bearing area of the femur and tibia can only be properly evaluated after 10 to 20 years of follow-up. In order to obtain functional results, meniscal allografts have to be incorporated in the knee joint by intimate meniscofemoral synovial bonding. The synovial fibroblasts must grow into the collagen meshwork of the meniscal allograft. Such ingrowth has been shown in freeze-dried and deep-frozen meniscal allografts. However, in a small number of transplants shrinking has been observed on repeat arthroscopy at 6 months. Satisfactory incorporation of meniscal allografts has been obtained with fresh allografts, but availability remains a problem when this method is used for meniscal substitution. For this reason viable meniscal allograft implantation was initiated in a series of 25 patients and the value of this method studied. The meniscal allograft can be kept in an adequate semisynthetic nutrient medium for approximately 2-3 weeks without apparent loss of viability, during which period the appropriate recipient can be selected and prepared, a thorough laboratory screening can be conducted, and the culture results and disease transmission factors can be evaluated. In this way, live transplant hazards can be avoided, resulting in a higher success rate. PMID- 8190509 TI - [Transplantation of allogeneic menisci]. AB - The increase in severe ligament injuries of the knee has led to consideration of the need for meniscal transplantation in reconstructive operations for chronic rotational instability. Transplantation of the medial meniscus was carried out in 30 sheep, which were divided up into 2 groups, each containing 15 sheep. In the first group lyophilized, y-sterilized allogeneic menisci were transplanted and these underwent complete remodelling in 48 weeks. In the other group, deep-frozen allogeneic menisci were used and these remained fully functional without remodelling. Twenty-three transplantations of the medial meniscus combined with replacement of the anterior cruciate ligament were performed from May 1984 to December 1986. Clinical follow-ups were coupled with arthroscopic follow-ups on an average of 10 months post-operatively in 19 sheep. In 17 cases a lyophilized meniscus was transplanted and in 6 cases a deep-frozen allogenous meniscus was used. There were no operation-specific complications in either group. Both the lyophilized meniscus transplants and the deep-frozen ones underwent a reduction in size during the observation period. Good-to-excellent results were generally obtained with the deep-frozen transplants; however, there is the risk of transmitting disease. The results seen in the lyophilized transplants were less satisfactory due to a reduction in size, sometimes down to the regeneration size. Taking the infrapatellar fatty pad for meniscal replacement (as suggested by Lexer), we saw only weak meniscus-like tissue after the first year postoperatively. The meniscus tendon by means of an autologous tendon for meniscus replacement may be an alternative procedure. Therefore, allogeneic meniscus transplantation for reconstruction of the knee joint cannot be recommended at present as a standard procedure. PMID- 8190510 TI - [Meniscus replacement]. AB - Partial meniscectomy and meniscus reconstruction are the procedures of choice for the majority of symptomatic meniscus lesions. If total meniscectomy cannot be avoided or was already performed, there is a risk of osteoarthritis, especially in the unstable knee. Different approaches of meniscus replacement are under experimental and clinical investigation at present. Replacement by a tendon autograft, by a meniscus allograft, by a prosthesis or by a collagenous scaffold are discussed. This article is an up-date on the current situation today. PMID- 8190511 TI - [Assessment of the relationship between trauma and meniscal lesions]. AB - Until the 1930s all meniscal lesions were considered to be of traumatic origin. The efforts of Magnus and his pupils led to a more differentiated medicolegal interpretation of wear and tear of the meniscus and classification of at least some types of meniscal lesions as nontraumatic in the sense of accident insurance. This caused controversy, continuing to the present day, as to whether trauma or degeneration is essential for a meniscal tear. This debate can now be closed. Numerous investigations of meniscus pathology have proved that the isolated, essentially traumatic meniscal tear does not exist. Only if the viscoelastic properties of meniscus tissue are changed may indirect force cause a rupture. There is no longer any reason to follow principles for the assessment of meniscus damage differing from those for tendon or intervertebral disc lesions. Only penetrating joint injuries or joint fractures may lead to a direct meniscal lesion (corresponding to penetrating spine trauma or vertebral body fracture with concomitant disc lesion). Separation of the meniscus from its insertion is the analog of discoligamentous spinal trauma. Post-traumatic meniscus degeneration due to joint instability is equivalent to the instability of the motion segment with intervertebral disc degeneration. Isolated meniscal tears and isolated intervertebral disc ruptures cannot be caused by indirect force. The conventional, inconsistently applied criteria to distinguish traumatic and degenerative meniscal lesions are no longer necessary. PMID- 8190512 TI - [Biomechanics of the meniscus]. AB - The menisci of the knee joint enlarge the area of support to more than twice the surface of pure cartilage contact. As a result of the wedge-shaped cross-section, the meniscus is stressed by radially directed shear forces, but because of the bone attachment at both ends, the shear forces are transformed into circular tensile stress. The arrangement of collagen fibres reflects the pattern of tensile stress trajectories. Single chondroma are found in the peripheral zone. The range of displacement of the knee is considerably widened by the menisci. After meniscectomy, this function can be compensated for by the cruciate ligaments, but the stress on the articular cartilage will then increase. PMID- 8190513 TI - [Menisci and knee stability]. AB - The menisci are of primary importance for the knee and its stability. They assure functional congruence guided by the crucial ligaments. They break up the greatest amount of contact-impact force and limit "elastically" rotation and translation movements. They are polyfunctional. That is the reason why it is so difficult to measure their physiologic behavior and mechanical effects. The medial and lateral compartments, and therefore the medial and lateral meniscus function and anatomy, are not symmetric but are quite different. The menisci are important for "fine tuning" in the control of normal motion and its limits. By achieving functional congruity they create stability ex vacuo, as in the shoulder joint. PMID- 8190514 TI - [Meniscus insertion]. AB - In meniscus replacement procedures anatomically correct fixation of the graft is one of the prerequisites for a successful outcome. An anatomical cadaver study was carried out to identify the insertion areas in the femur and tibia as well as the peripheral meniscus length. Ninety-two fresh knees from 46 human donors were included. The tibial insertions of the medial meniscus could be defined by bony landmarks. The peripheral length was 111 +/- 11 mm for the medial and 110 +/- 13 mm for the lateral meniscus. Wrisberg's ligament was present in 76% of all knee specimens and Humphry's ligament could be found in 50%. The correlation between the right and left knee in the same individual was poor concerning the presence of the meniscofemoral ligaments and the size of the tibial meniscal insertions to bone. PMID- 8190515 TI - Human fetal antibody-dependent cellular cytotoxicity to herpes simplex virus infected cells. AB - Human fetal antibody-dependent cellular cytotoxicity (ADCC) has not been reported previously. Most investigations have failed to document any cytolytic activity among fetal lymphocytes. The purpose of this study was to investigate ADCC activity in the human fetus and identify and characterize the effector cell populations in the fetus. Fetal spleen cells were separated into single-cell suspensions and assayed with 51Cr-labeled herpes simplex 1-infected Chang liver target cells. Significant ADCC activity was detected in 19 of 26 (73%) of freshly assayed fetal spleen cell preparations from fetuses of 17-24 wk gestational age. This activity, however, was significantly less than concurrently run adult peripheral blood mononuclear cells. After plastic adherence the fetal spleen ADCC activity from nonadherent cells was not significantly different from whole spleen preparations. Surprisingly, ADCC activity in nonadherent fetal cells dropped significantly after exposure to latex beads, an effect not seen in nonadherent adult lymphocytes. Thus, either fetal monocyte-derived (macrophages) fetal spleen cells do not efficiently adhere to plastic or a unique nonadherent population of latex-sensitive immunocytes is capable of mediating ADCC activity in the fetus. We suspect the former conclusion to be the more plausible; however, fluorescence activated cell sorter staining of fetal cells was not sufficient to confirm these suspensions by fluorescence-activated cell sorter analysis. PMID- 8190516 TI - Proliferative and cytokine responses by human newborn T cells stimulated with staphylococcal enterotoxin B. AB - Staphylococcal enterotoxins are potentially valuable tools for investigating the development of T-cell responses because in experimental animals they can elicit either T-cell activation and proliferation or tolerance. Previous studies indicate that human T cells bearing the CD45RA phenotype (which account for the majority of newborn T cells) respond poorly to stimulation by staphylococcal enterotoxin B (SEB) compared with mature T cells from adult blood. The present studies show that the mean frequency of newborn T cells that proliferated in limiting dilution cultures stimulated by SEB was 1:3135, with a 1SD range of 3153 4191 compared with a mean of 1:493 and range of 120-1737 for adult T cells. Neither indomethacin nor the nitric oxide synthesis inhibitor, n-arginine methyl ester, increased SEB responses by newborn cells, arguing against down-regulation of the newborn response by prostaglandin or nitric oxide. Naive (CD45RA+) T cells from adult blood had a responder cell frequency to SEB similar to that of the newborn cells. IL-2 production by newborn cells was delayed compared with adult cells but was equivalent after 3 d of culture. Production of gamma-interferon and IL-4 was greater by adult than newborn cells. Our results indicate that a subset of CD45RA+ cells that is activated by SEB can mature to make IL-4 or gamma interferon after 3-5 d. The limiting dilution assay results provide a quantitative basis for proliferation by naive T cells against which responses by T cells from healthy and premature newborns can be compared. PMID- 8190517 TI - Impaired synthesis of lipoxygenase products in glutathione synthetase deficiency. AB - Glutathione synthetase deficiency (GSD) is an inborn error of glutathione (GSH) metabolism leading to a generalized intracellular GSH deficiency. Because GSH is required for leukotriene C4 (LTC4) synthesis, we studied synthesis and metabolism of several lipoxygenase products in two patients with GSD by radio-HPLC, UV spectrophotometry, and enzyme immunoassays. In both patients, LTC4 synthesis was significantly decreased in calcium ionophore-stimulated neutrophils (up to 0.4 ng/10(6) cells; controls, 5.0 +/- 0.9) and monocytes (up to 3.6 ng/10(6) cells; controls, 30.2 +/- 3.3). LTB4 synthesis was about seven times higher in GSD cells compared with controls, whereas synthesis of other 5-, 12-, and 15-lipoxygenase products and prostaglandin E2 was not affected. Neutrophils and monocytes from both patients showed a marked reduction in capacity to form [3H]LTC4 from [3H]LTA4 (9-14% of control values). Urinary LTE4 was finally found to be 50-fold lower in GSD, reflecting a decreased synthesis of cysteinyl LT in vivo. GSD may serve as a unique model for the linkage between LT synthesis and GSH metabolism in vivo. PMID- 8190518 TI - Endotoxin induces glutathione reductase activity in lungs of mice. AB - Glutathione reductase catalyzes the NADPH-dependent conversion of glutathione disulfide to glutathione and helps protect the lung from injury by reactive oxygen. In animals allowed to breathe nearly 100% oxygen, the activities of other antioxidants in the lung can be induced by treatment with endotoxin, and this induction is associated with increased tolerance to hyperoxia. The purpose of this study was to see whether glutathione reductase activity in the lungs of mice increased with endotoxin treatment alone. We studied 60 FVB mice (20 males and 40 females). Half received endotoxin (500 micrograms/kg) intraperitoneally at time 0 and 24 h, and the controls received an equal volume of saline. At 48 h we killed the mice and removed their lungs. Treatment of mice with endotoxin increased glutathione reductase activity in the lung 55% (0.035 +/- 0.005 to 0.054 +/- 0.010 mumol NADPH reduced/min/mg protein; mean +/- SD; endotoxin different from control, p < 0.001). The increase in activity was the same for male and female mice. We measured the specific protein for glutathione reductase by Western analysis and mRNA for glutathione reductase using a slot-blot analysis and found that both increased roughly 2-fold with endotoxin treatment. This suggests that endotoxin treatment resulted in either increased rate of transcription of glutathione reductase mRNA or increased mRNA stability. We conclude that endotoxin treatment increases glutathione reductase activity in the lung and that this increase in activity may play a role in subsequent protection from hyperoxia. PMID- 8190519 TI - The respiratory response of healthy term infants to breath-by-breath alternations in inspired oxygen at two postnatal ages. AB - We have studied the reflex respiratory responses to breath-by-breath alternations in fractional inspired oxygen in a group of healthy term infants at two ages, 43 +/- 7 h (study 1) and 47 +/- 3 d (study 2). Respiration was measured noninvasively using inductance plethysmography. Responses to alternations of fractional inspired oxygen between 0.16 and 0.21 (test runs) were compared with responses to alternating the inspired gas between two lines each containing a fractional inspired oxygen concentration of 0.21 (control runs). The respiratory response was measured as the mean percentage breath-by-breath alternation for inspiratory tidal volume (VTI), expiratory tidal volume (VTE), inspiratory time (TI), expiratory time (TE), frequency (f), mean inspiratory flow (VTI/TI), mean expiratory flow (VTE/TE), timing (TI.f), and ventilation. A significant chemoreflex response was present in the infants at the time of study 1, as shown by test runs that were significantly different from control for TI, TE, f, mean inspiratory flow, mean expiratory flow, timing, and ventilation (p < 0.05), and at study 2 for VTI, VTE, TE, f, mean inspiratory flow, mean expiratory flow, timing, and ventilation (p < 0.05). When control and test runs were compared separately with respect to age, there were no significant differences for any respiratory variable between study 1 and study 2. Thus, we did not observe significant maturation of respiratory chemoreflex responses to hypoxia after an age at which we could detect an established response, and this suggests that the "resetting" of chemoreceptor responses to hypoxia is essentially complete within approximately 24-48 h of birth in humans. PMID- 8190520 TI - Atrial myocardial blood flow during acute right ventricular pressure load and adenosine infusion in late gestation fetal sheep. AB - The purpose of this study was to investigate atrial myocardial blood flow in the fetus under conditions of acute right ventricular pressure load and adenosine infusion. Late gestation fetal sheep were instrumented for acute right ventricular pressure loading or adenosine infusion, and regional myocardial blood flow was measured at rest and under experimental conditions with radiolabeled microspheres and standard reference sample technique. Resting myocardial blood flow to the atria was less than half of ventricular flow per gram tissue. During the maximum tolerated pulmonary artery pressure load, right atrial peak systolic pressure rose significantly, and atrial blood flow increased 3-fold. The percentage of total myocardial blood flow received by the right atrium during maximal pressure loading increased from 4.3 +/- 1.4% to 5.9 +/- 1.6%, p < 0.05. Adenosine infusion was associated with a 4-fold increase in atrial myocardial blood flow and a 3-fold increase in ventricular and septal blood flow. The percentage of total myocardial blood flow to both atria also increased with adenosine infusion (right atrium, 3.8 +/- 0.4% to 5.4 +/- 1.3%, and left atrium, 4.2 +/- 0.8% to 6.9 +/- 2.0%, p < 0.05). We conclude the following: 1) at rest, fetal atrial myocardial blood flow is less than one half of ventricular myocardial blood flow per gram tissue; 2) fetal atrial blood flow increases more than ventricular blood flow with acute right ventricular pressure load or adenosine infusion; and 3) these data suggest that fetal atrial blood flow is regulated independently from ventricular blood flow and may be influenced by atrial work. PMID- 8190521 TI - Relationship between brain blood flow and carotid arterial flow in the sheep fetus. AB - The present study investigates whether changes in total brain blood flow can be reliably estimated by changes in carotid arterial blood flow in fetal and perinatal lambs. We therefore compared carotid arterial blood flow, measured with implanted transit-time ultrasound transducers, with brain blood flow, measured by radioactive microspheres in fetal lambs during normal oxygenation and during pulmonary ventilation with oxygen, with PO2 ranging from levels normal for the healthy fetus to levels normally seen postnatally. Cerebral perfusion pressure was modified over a wide range to alter brain blood flow: it was decreased by balloon occlusion of the brachiocephalic trunk and increased by a balloon occluder around the aortic isthmus. Carotid arterial blood flow and brain blood flow were closely related (r = 0.97, p < 0.0001). The relationship was not altered at different levels of oxygenation. However, measurements during higher cerebral perfusion pressures, obtained during aortic isthmus occlusion, had a negative influence on the agreement between carotid arterial blood flow and brain blood flow. When excluding values obtained by aortic isthmus occlusion, changes of 20% or more in brain blood flow could be predicted with carotid arterial blood flow within a confidence limit of 95%. Blood flow measurements in the carotid artery may be useful to estimate changes in brain perfusion. PMID- 8190522 TI - Monitoring of the intracranial hemodynamics and oxygenation during and after hyperventilation in newborn rabbits with near-infrared spectroscopy. AB - Oxyhemoglobin, deoxyhemoglobin, total hemoglobin, and oxidized cytochrome aa3 were monitored, blood pressure and heart rate were continuously recorded, and cerebral hemodynamic changes were analyzed during and after hyperventilation (arterial CO2 tension < 2.67 kPa) and/or hyperoxemia (100% O2 inhalation) in 11- to 12-d-old rabbits. Oxyhemoglobin, deoxyhemoglobin, total hemoglobin, and oxidized cytochrome aa3 were monitored by means of near-infrared spectroscopy. Near-infrared spectroscopy ideally demonstrated decreases in oxyhemoglobin and total hemoglobin and an increase in deoxyhemoglobin during hyperventilation and a return to the previous values after hyperventilation. Cytochrome aa3 decreased during hyperventilation. On hyperventilation with 100% O2 inhalation, however, cytochrome aa3 was not reduced, although the changes in oxyhemoglobin and total hemoglobin were more significant. This reduction of cerebral oxygenation during hyperventilation without the administration of oxygen may induce hypoxic-ischemic brain damage. Noninvasive monitoring of cerebral oxygenation and hemodynamics, for which near-infrared spectroscopy is useful, is a requisite for the prevention of brain injury caused by severe hypocarbia in hyperventilation therapy. PMID- 8190523 TI - Cerebral responses to single and multiple cocaine injections in newborn sheep. AB - Newborn infants exposed to cocaine near birth display a wide range of neurologic abnormalities, but the mechanism or mechanisms for these injuries remain unknown. We studied the cerebral effects of a single acute dose (4 mg/kg; n = 7) and multiple binge doses (4 mg/kg hourly for 5 h; n = 7) of i.v. cocaine in unanesthetized newborn (5 +/- 1 d old) sheep. We measured cerebral blood flow, mean arterial blood pressure, arterial blood gases, and cerebral O2 metabolism. Measurements were made at baseline; 30 s; and 5, 15, and 60 min after a single injection of cocaine in the acute group and at the same time intervals after the 5th dose of cocaine in the binge group. CBF increased by 98 +/- 68% (mean +/- SD) at 30 s after a single acute dose and by 97 +/- 94% at 30 s after the 5th of five hourly binge doses. Although it returned to baseline by 5 min in the acute group, cerebral blood flow remained elevated 5, 15, and 60 min after the 5th cocaine dose in the binge group. At 30 s, mean arterial blood pressure increased by 57 +/ 21% in the acute group and 46 +/- 15% in the binge group. In both groups, mean arterial blood pressure remained elevated at 5 min. Although no change occurred in cerebral O2 metabolism in the acute group, an increase in cerebral O2 consumption (7.4 +/- 1.3 mL/100 g/min versus 5.5 +/- 1.1 at baseline) was observed at 5 min in the binge group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190524 TI - Human alpha-lactalbumin and bovine beta-lactoglobulin absorption in premature infants. AB - The absorption of alpha-lactalbumin (ALA) and bovine beta-lactoglobulin (BLG) was investigated in 23 healthy preterm infants with gestational ages of 32 to 36 wk. The concentrations of ALA and BLG in serum after a milk feeding were measured at intervals during the first 8 mo of life. We used a time-resolved fluoroimmunoassay to measure the proteins. Measurable amounts of ALA were found on d 7 after birth, and at 1, 2, 3, 5, and 8 mo in 23 of 23, 13 of 18, 13 of 18, six of 17, eight of 16, and five of 13, respectively, of the infants tested; median serum levels of ALA at the respective ages were 120 (range, 19-2598), 16 (range, 0-177), 5 (range, 0-40), 0 (range 0-3), 0.8 (range 0-38), and 0 (range, 0 22) micrograms/L serum/g ALA given/kg body wt, respectively. The rate of decline in ALA absorption was comparable among the infants. Tests for BLG were begun after the introduction of cow's milk. At 2, 3, 5, and 8 mo of age BLG was detected in two of 7, two of 9, eight of 10, and two of 12, respectively, of the infants tested, where median levels in positive cases were 13, 17, 15, and 3 micrograms/L serum/g BLG given/kg, respectively. The amounts of absorbed ALA and BLG were 10(-5) to 10(-3) of the oral dose. Serum levels of ALA or BLG did not depend on the gestational age of the infant. Few of the infants had any detectable absorption of either protein shortly after weaning.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190525 TI - The presence of transforming growth factor-alpha in the suckling rat small intestine and pancreas and the absence in rat milk. AB - Immunoreactive rat transforming growth factor-alpha (TGF-alpha) was measured in rat milk, in the mucosa and lumen of the small intestine, and in the pancreas of suckling and adult rats with a homologous RIA. In contrast to epidermal growth factor, where the main source of epidermal growth factor for sucklings is rat milk, the presence of TGF-alpha was not detectable in rat milk. The concentrations of TGF-alpha in the small intestine exhibited similar values in suckling and adult rats, whereas epidermal growth factor levels in the small intestine were several times higher in suckling rats than adults. Overnight fasting in suckling rats resulted in minimal changes in the luminal and mucosal TGF-alpha content. A positive correlation was established in suckling rats between the TGF-alpha content in the intestinal lumen (but not mucosa) and the TGF-alpha content in pancreas. Despite many structural and functional similarities between TGF-alpha and epidermal growth factor, our present data indicate significant differences in the origin and distribution of these two growth factors in the tract of the small intestine of developing rats. PMID- 8190526 TI - Loperamide inhibits the enhanced intestinal glucose absorption of cystic fibrosis in vitro. AB - Enhanced Na(+)-linked nutrient absorption has been demonstrated in the cystic fibrosis bowel and may contribute to the dehydration of the luminal contents. The ability of loperamide to inhibit glucose transport was therefore assessed in jejunal biopsy specimens from children with cystic fibrosis by measuring the increased short-circuit current associated with active glucose absorption using a mini-Ussing chamber technique. The presence of loperamide in the luminal solution reduced the rise in short-circuit current induced by glucose over the range of concentrations tested (2.5 to 40 mmol.L-1). This finding suggests that the enhanced Na+ absorption, which is a feature of cystic fibrosis, is amenable to treatment and can be restored to normal levels. This result may have therapeutic implications for gastrointestinal function and may be applicable to other tissues where similar therapeutic approaches to reduce Na+ and thus water absorption are being pursued. PMID- 8190527 TI - Removal of branched-chain amino acids by peritoneal dialysis, continuous arteriovenous hemofiltration, and continuous arteriovenous hemodialysis in rabbits: implications for maple syrup urine disease treatment. AB - Renal elimination of branched-chain amino acids (BCAA) is low in maple syrup urine disease, and peritoneal dialysis may be required in an emergency situation for removal of the three BCAA (leucine, isoleucine, and valine). However, failures of BCAA removal by peritoneal dialysis have been reported, especially in neonates. Therefore, we tested the ability of continuous hemofiltration and continuous hemodialysis to remove BCAA as compared with peritoneal dialysis. Experiments were conducted in 15 anesthetized adult rabbits infused with leucine, isoleucine, and valine. In group 1 (n = 7), peritoneal dialysis (dialysate = 75 mL/kg) and continuous arteriovenous hemofiltration with a polysulfone 800-cm2 hemofilter were simultaneously performed during 40 min. In group 2 (n = 8), continuous arteriovenous hemofiltration and continuous arteriovenous hemodialysis were successively performed during 30 min in a randomly settled order. Animals had high and stable BCAA plasma levels during the experimental procedure. As compared with peritoneal dialysis, continuous arteriovenous hemofiltration constantly showed a significant increase in clearances of leucine (+159 +/- 99%), isoleucine (+176 +/- 107%), and valine (+125 +/- 76%). In comparison with continuous arteriovenous hemofiltration, continuous arteriovenous hemodialysis constantly showed significant increased values in clearances of leucine (+90 +/- 43%), isoleucine (+95 +/- 45%), and valine (+99 +/- 52%). During continuous arteriovenous hemofiltration and continuous arteriovenous hemodialysis, a significant positive correlation was established between urea clearance and clearances of leucine (r2 = 0.953 and 0.927, respectively), isoleucine (r2 = 0.948 and 0.910, respectively), and valine (r2 = 0.953 and 0.864, respectively). PMID- 8190528 TI - Bone mineral density of the lumbar spine in white Mediterranean Spanish children and adolescents: changes related to age, sex, and puberty. AB - Bone mineral content was measured by dual-energy x-ray absorptiometry in the lumbar spine at the L2-L4 level with a Lunar DPX densitometer model in 471 healthy white Mediterranean Spanish children and adolescents (256 boys and 215 girls) randomly selected from the urban area of Barcelona. Ages ranged from 3 mo to 21 y. Weight, height, and pubertal development were in the normal age distribution. Bone mineral content values were corrected by the vertebral surface area scanned and expressed as bone mineral density (BMD) values. BMD increased progressively from infancy to adulthood, and values were similar in both sexes, with the only differences related to the earlier onset of puberty in girls. A statistically significant correlation (p < 0.001) was found between BMD values and age, height, and weight. BMD values increased annually, but the periods of higher increase were observed during the first 3 y of life and late puberty. A significant (p < 0.001) increase in BMD was observed between Tanner pubertal stages III and IV and between Tanner stage IV and adult values. Lumbar BMD values peaked in a similar way to growth height velocity during pubertal development. However, the BMD peak seemed to occur somewhat later than height velocity peak, particularly in girls. In conclusion, we report normative data for BMD values at the lumbar level in our normally growing pediatric population and show that the first 3 y of life and adolescence are critical periods for bone mineralization. These data provide a tool for the investigation and follow-up of pediatric populations at risk for low bone mineralization. PMID- 8190529 TI - Growth after renal transplantation in prepubertal children: impact of various treatment modalities. AB - A retrospective study evaluated posttransplant growth of 70 prepubertal children during the first 2 y after renal transplantation (RTx). Immunosuppressive treatment consisted of prednisone administered either daily or on alternate days in combination with either azathioprine or cyclosporin A. The increment in height standard deviation score for chronologic age during the first 2 y after RTx was less than 0.5 SD for 70% of the study population. The predictive factors for posttransplant growth were determined by evaluating several factors and treatment modalities singly and simultaneously in a multiple regression analysis. Patients with the most severe growth retardation at RTx appeared to have the most pronounced growth spurt after RTx, but even they never had complete catch-up growth, and 2 y after RTx they were still shorter than those with less severe growth retardation at RTx. Alternate-day instead of daily prednisone administration had a significantly positive influence, whereas a high cumulative dose of prednisone, azathioprine instead of cyclosporin A therapy, and a persistently reduced GFR (GFR < 50 mL/min/1.73 m2) had a significantly negative influence on catch-up growth during the 2 y after RTx. Other factors, such as gender, chronologic and bone age at RTx, primary renal disease, duration of initial dialysis, repeat RTx, and target height SD score for chronologic age, whether evaluated singly or simultaneously with other significant factors, appeared to have no significant influence on post-RTx growth. Thus, 70% of the prepubertal children do not experience appreciable catch-up growth during the first 2 y after RTx. Optimization of pretransplant height appears very important. Immunosuppressive treatment with cyclosporin therapy in combination with a minimal dose of alternate-day prednisone would then result in optimal post transplant growth, particularly if the GFR remains above 50 mL/min/1.73 m2). PMID- 8190530 TI - Reduced Na+, K(+)-ATPase activity in patients with pseudohypoaldosteronism. AB - Pseudohypoaldosteronism is a hereditary salt-wasting syndrome usually seen in infancy with weight loss, dehydration, and failure to thrive. The pathophysiologic origin of pseudohypoaldosteronism is unknown. The defect could be related to the unresponsiveness of target organs to mineralocorticoids resulting in hyponatremia, hyperkalemia, and markedly elevated plasma aldosterone and renin levels. Red blood cell Na+, K(+)-ATPase activity was measured in a pair of twins with pseudohypoaldosteronism, in an unrelated child with hypoaldosteronism, and in an age-matched group of 50 healthy infants and young children. The enzyme was assayed by a method that couples ATP hydrolysis with NADH oxidation. Plasma renin and aldosterone levels were measured by RIA. Red blood cell Na+, K(+)-ATPase activity in the twins with pseudohypoaldosteronism was very low at the time of diagnosis (3 wk). In both twins a time-related gradual increase in enzyme activity was observed during the 1st mo of life, reaching control values between 6 and 8 mo of age. This increase was associated with both a reduction in salt requirement and clinical improvement. Plasma renin activity and aldosterone levels were very high at the time of diagnosis. Plasma renin activity reverted gradually to normal values, whereas aldosterone levels remained high throughout the follow-up period. The child with hypoaldosteronism had normal Na+, K(+)-ATPase activity at diagnosis and during follow-up. PMID- 8190531 TI - Effect of diabetes mellitus on maternofetal flux of calcium and magnesium and calbindin9K mRNA expression in rat placenta. AB - The effect of maternal diabetes mellitus on placental unidirectional maternofetal flux of calcium (Ca) and magnesium (Mg), calbindin9K mRNA expression, and net fetal Ca and Mg accretion has been investigated using control (C), untreated diabetic (D(O)) and insulin-treated diabetic (DI) rats. Unidirectional maternofetal flux of Ca in the D(O) group was 61 and 63% of the value of the C and DI groups; unidirectional maternofetal flux of magnesium in the D(O) group was 79 and 66% of the value in the C and DI groups. Fetal Ca and Mg content (mmol; mean +/- SEM) was also significantly lower in the D(O) group compared with the other two groups (0.111 +/- 0.004 versus 0.153 +/- 0.008 in C and 0.168 +/- 0.007 in DI, p < 0.01 D(O) versus C and DI for Ca; and 0.021 +/- 0.001 versus 0.027 +/- 0.001 in C and 0.031 +/- 0.001 in DI, p < 0.01 D(O) versus C and DI for Mg). However, only Ca content was significantly lower in the D(O) group when normalized to fetal ash weight. Densitometric analysis of autoradiograms after Northern hybridization with cDNA probes demonstrated that the placental calbindin9K/cyclophilin mRNA ratio was 11- to 12-fold lower in the D(O) group compared with the C and DI groups. Collectively, the data suggest that untreated maternal diabetes mellitus reduces fetal Ca and Mg accretion by an effect on the expression of placental transport components involved in the maternofetal transfer of these cations. PMID- 8190532 TI - Aerosolized pentamidine for prophylaxis of Pneumocystis carinii pneumonia in infants with human immunodeficiency virus infection. AB - Aerosolized pentamidine is widely used in adult patients with human immunodeficiency virus as both prophylaxis and therapy for Pneumocystis carinii pneumonia. The aim of this study was to evaluate the safety of a monthly regimen of aerosolized pentamidine in human immunodeficiency virus-infected infants. Seven human immunodeficiency virus-infected infants, ages 3.5 to 11 months, were given a total of 45 monthly treatments of aerosolized pentamidine. The infant's dose of pentamidine was based on an adult dosage of 300 to 600 mg/month, adjusted for minute ventilation and weight. There were no discernible clinical side effects in 62% (28 of 45) of the treatments. Observed toxicity included mild to moderate coughing, mild wheeze and transient arterial desaturation as measured by pulse oximetry. Pulmonary function data revealed an increased tidal volume (P < 0.005) and an increased pulmonary resistance (P < 0.02) post-pentamidine treatment. Urinary pentamidine concentrations were obtained and pentamidine was detected in all tested samples suggesting pulmonary deposition and systemic absorption. In conclusion aerosolized pentamidine appears to be a relatively safe, well-tolerated treatment in infants, with side effects similar to those seen in adults. PMID- 8190533 TI - Nosocomial Malassezia pachydermatis bloodstream infections in a neonatal intensive care unit. AB - Malassezia pachydermatis, a lipophilic yeast, has been described to cause sporadic nosocomial bloodstream infections (BSI). Nosocomial outbreaks of M. pachydermatis BSI have never been described. A cluster of M. pachydermatis BSIs in the neonatal intensive care unit at Louisiana State University Medical Center, University Hospital provided the opportunity to investigate the epidemiology of this organism and apply molecular epidemiologic typing techniques. A case-patient was defined as any neonatal intensive care unit patient in University Hospital with a blood culture positive for M. pachydermatis from January 1, 1989, through August 15, 1991. Five patients met the case definition. Case-patients were premature as estimated by gestational age and required prolonged hospitalization. Case-patients received parenteral nutrition and intravenous lipids for twice as many days as randomly selected controls. No environmental source of M. pachydermatis was identified; however, infants on each side of a previously identified M. pachydermatis-colonized infant became colonized with M. pachydermatis during a 20-day period. Chromosomal analysis of five M. pachydermatis blood isolates from two case-patients had identical banding patterns. These data show that M. pachydermatis can cause nosocomial BSI outbreaks, that premature infants receiving parenteral nutrition and/or lipids may be at greatest risk and that transmission is most likely from person to person, probably via the hands of medical personnel. PMID- 8190534 TI - Long term impact of high titer Edmonston-Zagreb measles vaccine on T lymphocyte subsets. AB - Several trials of high titer measles vaccine (> 10(4.7) plaque-forming unit) have found female recipients of Edmonston-Zagreb (EZ) vaccine to have lower survival than female recipients of standard measles vaccine. Two trials with medium and high titer EZ vaccine from the age of 4 months were conducted in Guinea-Bissau. To test for possible long term impact on the immune system, an investigation of T cell subsets was conducted among all children still residing in the community at 3 to 5 years of age. No differences were found between recipients of medium titer vaccine and controls. In the second trial, however, recipients of high titer had lower CD4:CD8 ratios than controls and had significantly higher CD8 percentages and lower CD4:CD8 ratios than recipients of medium titer EZ. When analyzed by sex, differences were found only among the girls. However, these differences were small and seemed unlikely to explain the reduced survival which has been associated with high titer EZ measles vaccination. In the 2 years after the investigation of T cell subsets, there was no increased mortality for recipients of EZ vaccine. Hence it is unlikely that high titer vaccine has an persistent adverse effect on survival after 3 years of age. PMID- 8190535 TI - Osteitis after newborn vaccination with three different Bacillus Calmette-Guerin vaccines: twenty-nine years of experience. AB - Newborns in Finland have been vaccinated with Bacillus Calmette-Guerin (BCG) since the 1950s. Until the end of 1970 the vaccine was made from BCG strain Gothenburg by the Swedish BCG laboratory in Gothenburg and from 1971 on from the same strain in Copenhagen, Denmark. It was replaced by the Glaxo vaccine in 1978. Complications caused by BCG vaccination have been under follow-up, and the data have been collected from nationwide registers. In this study we analyzed the incidence rates of BCG osteitis between the years 1960 and 1988. From 1960 to 1970 the incidence rate was from 2.7 to 13.0/100,000 BCG-vaccinated infants (mean, 7.3; median, 6.9). The incidence increased during the years 1971 to 1978 when it varied between 15.3 and 72.9/100,000 BCG-vaccinated infants (mean, 36.9; median, 30.4). Since 1978 the incidence has varied between 1.7 and 10.1/100,000 BCG-vaccinated infants (mean, 6.4; median, 7.2). In Britain no reports of BCG osteitis have been published despite the use of the same Glaxo vaccine. Our results indicate that the incidence of BCG osteitis in a given population depends on the BCG vaccine used. The follow-up of BCG complications is an essential part of BCG vaccination program. PMID- 8190536 TI - Epidemiology of acute diarrheal diseases in children in a high standard of living rural settlement in Israel. AB - Epidemiologic patterns of acute diarrheal diseases in a high standard of living communal settlement, situated in a region endemic for enteric diseases, were evaluated by a historical prospective study of 284 children (12,064 child months) from August, 1988, through July, 1992. Three hundred eighty-three episodes of acute diarrhea were identified, yielding a rate of 0.38 episode per 12 child months. One hundred and children (35.6%) were reported to have 1 to 4 diarrheal episodes and 29 (10.2%) children had 5 or more diarrheal episodes during the follow-up period. The mean number of episodes of acute diarrhea per 12 child months in children ages 0 to 2 years was 2.28, in 2- to 6-year-olds 0.44, in 6- to 13-year-olds 0.12 and in 13- to 18-year-olds 0.03 (P < 0.001). Children less than 12 months of age had a lower incidence of acute diarrheal diseases during the months they were being breast-fed than children that were fed with formula during the same period (1.22 vs. 3.06 episodes per 12 child months, respectively; P < 0.001). Enteropathogens were isolated in 40% of diarrheal episodes in which stool cultures were obtained. The identification rates of the various enteropathogens were: diarrheagenic Escherichia coli, 11%; Shigella spp., 10%; Giardia lamblia, 10%; Salmonella spp., 4%; Staphylococcus aureus, 3%; Campylobacter jejuni, 1%. Potential interventions against acute diarrhea in this set up of a high standard of living rural community are education of caretakers and parents on hygienic practices that can prevent transmission of pathogens among the young children and encouraging mothers to breast-feed their children. PMID- 8190537 TI - Importance of enteric bacteria as a cause of pneumonia, meningitis and septicemia among children in a rural community in The Gambia, West Africa. AB - Two thousand eight hundred ninety-eight children younger than 5 years old were investigated during a 2-year period in a rural area of The Gambia for possible pneumonia, meningitis or septicemia. After clinical examination and appropriate investigations, 1014 children were diagnosed as having pneumonia, 31 as having meningitis and 100 as having septicemia. Nine hundred seven children had a final diagnosis of malaria including 702 who satisfied the World Health Organization criteria for a diagnosis of pneumonia. A bacterial etiology was established in 115 (11%) patients with a final diagnosis of pneumonia, in 25 (81%) with meningitis and in 29 (29%) with suspected septicemia. Overall the pneumococcus was the leading pathogen identified among children with pneumonia and meningitis and ranked third among those with septicemia. However, during the wet season, when malaria transmission was highest, 50% of blood culture isolates obtained from children satisfying the World Health Organization criteria for a diagnosis of pneumonia were Salmonella or coliform species, and the pneumococcus and Haemophilus influenzae type b accounted for only 43% of isolates. Thus enteric bacteria may be as important as those bacteria more usually associated with respiratory disease among children presenting with a clinical picture of pneumonia during the wet season. This finding has important implications for case management and surveillance for antibiotic resistance. PMID- 8190538 TI - Clinical significance of fungi isolated from cerebrospinal fluid in children. AB - We reviewed the isolation of fungi from cerebrospinal fluid (CSF) cultures at Texas Children's Hospital during the past 6 years to evaluate the significance of a positive culture and to identify potential risk factors. Thirty-seven fungal isolates were recovered from 23 patients representing 2% of all 1498 positive CSF cultures for the study period. Candida species accounted for 94.5% of all fungal isolates. Nine of the 23 patients were newborns and 8 of these were very low birth weight premature neonates. C. albicans was recovered from the CSF of all newborns. Eleven patients were children 4 months to 14 years old. Three patients had positive cultures of CSF obtained on postmortem examination. Leading potential risk factors for positive CSF cultures from neonates included antimicrobial therapy, prematurity, very low birth weight, umbilical catheterization, total parenteral nutrition, intubation and respiratory distress syndrome. For children beyond the newborn period, potential risk factors were antimicrobial therapy for concurrent bacterial infection, chronic systemic or central nervous system disease and central venous cathterization. Disseminated fungal infection was documented in 40% of all patients with positive CSF cultures. Fungi recovered from 7 (35%) of 20 live patients were considered contaminants. We conclude that true fungal meningitis in children is accompanied by multiple positive cultures from CSF or CSF and a second site. A single positive CSF culture for fungi should be considered significant when both CSF findings compatible with meningitis and associated risk factors are present. The isolation of fungi from a single CSF culture can be considered insignificant when CSF findings are within normal limits despite the presence of potential risk factors or vice versa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190539 TI - Multidrug-resistant typhoid fever in children: epidemiology and therapeutic approach. PMID- 8190540 TI - Herpes simplex meningitis in infancy. PMID- 8190541 TI - Intrauterine adenoviral myocarditis presenting as nonimmune hydrops fetalis: diagnosis by polymerase chain reaction. PMID- 8190542 TI - Outbreak and control of varicella in a neonatal intensive care unit. PMID- 8190543 TI - Use of polymerase chain reaction for diagnosis of tuberculous meningitis. PMID- 8190544 TI - Meningococcus with reduced susceptibility to penicillin isolated in the United States. PMID- 8190545 TI - Development of Hansenula anomala infection in a child receiving fluconazole therapy. PMID- 8190546 TI - Bronchoesophageal fistulas secondary to coccidioidomycosis. PMID- 8190547 TI - Pathogenicity of cat-scratch disease bacilli. PMID- 8190548 TI - Splenectomy and viral vaccines. PMID- 8190549 TI - Safety of rifabutin in a three-month-old infant. PMID- 8190550 TI - Erythromycin lactobionate toxicity in preterm neonates. PMID- 8190551 TI - A four-year-old child with teicoplanin allergy but no evidence of cross-reaction with vancomycin. PMID- 8190552 TI - Primary human herpesvirus 7 infection and exanthema subitum. PMID- 8190553 TI - Seroprevalence of human herpesvirus 7 in patients with Kawasaki disease. PMID- 8190554 TI - Management of the febrile, otherwise healthy child with neutropenia. PMID- 8190555 TI - Recurrent ocular herpes simplex infection. PMID- 8190556 TI - Antimicrobial drug suspensions: a blinded comparison of taste of twelve common pediatric drugs including cefixime, cefpodoxime, cefprozil and loracarbef. AB - We conducted a blinded taste test evaluating 12 antimicrobial suspensions by smell, texture, taste, aftertaste and overall acceptance. Drugs received cumulative scores in each category as well as a total score ranking. Overall Lorabid scored highest but not significantly higher than Keflex, Suprax and Ceclor, all of which score higher than the other test drugs. Cefzil and Augmentin scored just below this group of drugs and higher than all other test drugs. Vantin was inferior to these drugs primarily because of its low score in aftertaste. It was ranked along with V-Cillin-K, Veetids, Sulfatrim and Pediazole, the lowest scoring group of drugs other than Dynapen which scored lower than all other test drugs. No difference overall was detected between the two penicillin VK suspensions evaluated, V-Cillin-K and Veetids. PMID- 8190557 TI - A comparative study of human immunodeficiency virus culture, polymerase chain reaction and anti-human immunodeficiency virus immunoglobulin A antibody detection in the diagnosis during early infancy of vertically acquired human immunodeficiency virus infection. AB - The infection status of 91 infants born to mothers with human immunodeficiency virus (HIV) infection was determined. Twenty-eight (31%) infants had confirmed HIV infection and 63 (69%) had seroreverted to HIV and lack evidence of infection. During the first 6 months of life HIV culture had a sensitivity and specificity for diagnosis of HIV infection of 80 and 100%, respectively. False negative HIV cultures were observed in only 7 of 35 specimens, 6 from among the 12 infected infants tested at birth. The sensitivity and specificity of polymerase chain reaction (PCR) detection of HIV were 95 and 93% respectively. A single false negative PCR test result was observed among the 19 tests performed on specimens from HIV-infected infants. False positive PCR test results were observed occasionally throughout the first 6 months of life. Detection of HIV specific IgA antibody lacked diagnostic sensitivity; positive test results were observed in only 53% of specimens obtained from infected infants. Culture and PCR detection offer excellent sensitivity and specificity for diagnosis of HIV infection during the first 6 months of life; however, false-negative HIV cultures sometimes are observed, particularly during the newborn period, and either false negative or false positive PCR test results may be noted occasionally. For purposes of clinical decision-making, any positive test result should be confirmed with a second HIV culture or PCR test performed on a separate blood specimen. PMID- 8190559 TI - Summary of major changes in the 1994 Red Book: American Academy of Pediatrics. Report of the Committee on Infectious Disease. PMID- 8190558 TI - Maternal human immunodeficiency virus 1 infection and intrauterine growth: a prospective cohort study in Butare, Rwanda. AB - A prospective cohort study of 318 human immunodeficiency virus 1 (HIV-1)-infected and 309 seronegative pregnant women was carried out in Butare, Rwanda. Birth weight was significantly lower among singleton infants born alive to HIV-1 infected mothers compared with those born alive to seronegative mothers (2706 g vs. 2825 g; P = 0.002). Crown-to-heel length, head circumference, chest circumference and placental weight were also reduced. Maternal HIV-1 infection was significantly associated with intrauterine growth retardation but not with preterm birth. Differences in the body mass index and weight/head ratio suggest that the adverse impact on live born infants may have been most severe towards the end of pregnancy, resulting in a lean infant with a relatively large head. The higher frequency of intrauterine growth retardation could not be explained by potential confounding factors such as maternal cigarette smoking, history of sexually transmitted diseases or sociodemographic characteristics. The neonatal physical examination did not reveal any differences in clinical signs or symptoms within 48 hours of birth except for the presence of conjunctivitis which was more common among infants of HIV-1-infected mothers. The perinatal and neonatal mortality rates were not significantly affected by maternal HIV-1 status. PMID- 8190560 TI - Apparent insatiability: an unrecognized manifestation of food intolerance in breast-fed infants. PMID- 8190561 TI - Prenatal genetic diagnosis for pediatricians. American Academy of Pediatrics Committee on Genetics. PMID- 8190562 TI - The application of health and safety guidelines to out-of-home child care programs. American Academy of Pediatrics Committee on Early Childhood, Adoption, and Dependent Care. PMID- 8190563 TI - Graduate medical education and pediatric workforce issues and principles. Task Force on Graduate Medical Education Reform. Federation of Pediatric Organizations. PMID- 8190564 TI - Circumcision questions. PMID- 8190565 TI - Circumcision questions. PMID- 8190566 TI - DDAVP approval question. PMID- 8190567 TI - Family-centered care. PMID- 8190568 TI - Family-centered care. PMID- 8190569 TI - Family-centered care. PMID- 8190570 TI - Why change the compression and ventilation rates during CPR in neonates? Neonatal Resuscitation Steering Committee, American Heart Association and American Academy of Pediatrics. PMID- 8190571 TI - The role of carnitine supplementation in valproic acid therapy. PMID- 8190572 TI - Does carnitine administration improve the symptoms attributed to anticonvulsant medications?: a double-blinded, crossover study. AB - OBJECTIVE: This study was designed to assess the reported improvement in "well being" perceived by parents when children who are taking anticonvulsant medications are administered carnitine. METHODOLOGY: Forty-seven children with seizures who were taking either valproic acid or carbamazepine were enrolled in a placebo-controlled, double-blinded, cross-over study of the effects of oral carnitine administration (100 mg/kilo) on their well-being as perceived by their parents. The well-being scores were assessed weekly by phone and in person at the start and end of each 4-week phase. RESULTS: The children's well-being scores improved weekly when either placebo or carnitine were administered. None of the analyses of improved well-being achieved statistical significance. CONCLUSION: We believe this study documents the necessity for controlled trials when assessing the subjective, beneficial effects of medications. Carnitine is expensive, costing approximately $.30/kilogram of body weight per day ($6 per day for a 20 kilo child). It would not appear warranted to administer carnitine prophylactically to children on anticonvulsant medications for alleviating common, nonspecific symptoms. Because there are no reliable clinical or laboratory tests of symptomatic carnitine deficiency caused by anticonvulsant administration, how to identify children in need of carnitine, and when to administer carnitine therapeutically to children receiving valproate or other anticonvulsants is unclear. PMID- 8190573 TI - Why are children hospitalized? The role of non-clinical factors in pediatric hospitalizations. AB - OBJECTIVE: Pediatric medical discharge rates vary widely across hospital service areas, beyond differences explained by chance or disease incidence alone. This study examines the relationship between the characteristics of local medical services and the likelihood of hospitalization. DESIGN: Small area and population based regression analysis. SETTING: The 72 hospital service areas of Maine, New Hampshire, and Vermont. STUDY POPULATION: The 589,290 (1989) children of Maine, New Hampshire, and Vermont < 15 years of age with 120,806 discharges during 1985 through 1989. MEASUREMENT AND MAIN RESULTS: Using logistic regression and controlling for community income, we found that children residing in zip codes with high per capita bed supply (4.0/1000) had 9% more discharges (odds ratio: 1.09; 99% confidence interval: 1.07, 1.11) compared with children in areas with low per capita bed supply (1.9/1000). Children living 30 minutes from the nearest hospital had 15% fewer medical discharges (odds ratio: 0.849; confidence interval: 0.830, 0.867) than those living in a zip code with a hospital. Residence in one of the three academic medical center hospital service areas resulted in 32% fewer discharges (odds ratio: 0.68; confidence interval: 0.66, 0.70). Similar and statistically significant (P < .01) results were noted for the most common nonperinatal diagnostic categories: asthma/bronchitis (diagnostic related group = 98) and gastroenteritis (diagnostic related group = 184). No effect was noted for femur fracture, a condition for which admission rates equal disease incidence. CONCLUSIONS: The supply and character of medical care are important influences on the likelihood of hospitalization for pediatric medical conditions for which outpatient alternatives are available. PMID- 8190574 TI - Evaluation of a rapid diagnostic test for respiratory syncytial virus (RSV): potential for bedside diagnosis. AB - OBJECTIVE: Rapid detection of respiratory syncytial virus (RSV) infection can assist clinicians in decisions regarding antiviral therapy with ribavirin as well as instituting infection control measures. The Abbott TestPack RSV is a rapid RSV detection immunoassay that can be performed on respiratory secretions in 20 to 30 minutes without special laboratory equipment. The purpose of this study was to evaluate housestaff performance of the TestPack RSV at bedside as compared with laboratory testing of aliquots of the same specimen by tissue culture inoculation, direct fluorescent antibody (DFA) testing and TestPack RSV. METHODS: During the 1991 through 1992 RSV season, 137 nasopharyngeal aspirates or washes obtained from pediatric patients < 4 years of age suffering from acute respiratory disease were assayed by the Food and Drug Administration-approved TestPack RSV as well as conventional tube culture and DFA testing. RESULTS: 66 of 137 (48%) specimens were positive for RSV as defined by: isolation and DFA positive (n = 48) and DFA testing positive with negative culture (n = 18); blocking assay experiments using TestPack RSV confirmed culture-negative DFA positive specimens as positive in 8/8 instances in which material for retesting was available. Using these definitions, the sensitivity and specificity for the assays were: housestaff TestPack RSV: 92%, 93%; laboratory TestPack RSV: 97%, 98%; virus isolation: 72%, 100%. CONCLUSION: From these data, it appears that the TestPack RSV EIA in the field setting is reliable, although laboratory confirmation of results is important. PMID- 8190575 TI - Efficacy of albuterol in the management of bronchiolitis. AB - OBJECTIVE: To examine the efficacy of albuterol (0.15 mg/kg per dose) in the management of bronchiolitis. DESIGN: Randomized, double-blind, placebo-controlled outpatient clinical trial utilizing four study groups: neubulized albuterol, nebulized saline, oral albuterol, and oral placebo. SETTING: Pediatric emergency department and outpatient clinic at University of Maryland in Baltimore. PATIENTS: Eighty-eight infants (median age 5.5 months) being treated for their first episode of wheezing were randomly assigned to nebulized albuterol (n = 22), nebulized saline (n = 23), oral albuterol (n = 19), oral placebo (n = 24). INTERVENTIONS: The nebulized groups received two nebulizations 30 minutes apart, whereas the oral groups received one oral dose. MAIN OUTCOME MEASURES: Respiratory and heart rates, clinical score, oxygen saturation (Spo2), and the infant's state, ie, asleep, awake, or feeding, were recorded at baseline and at 30 and 60 minutes after treatment. RESULTS: Randomization produced equivalent groups in terms of demographics and baseline measures. There were no statistically significant differences in any outcomes among the four treatments, except for oral albuterol, which produced an increase in heart rate (15 beats per minute, P = .005). No differences in the need for additional treatment or hospitalization were observed. Change in the state of the infant during the trial had significant effects on respiratory rate and clinical score. CONCLUSIONS: Albuterol is as effective as oral placebo in the management of bronchiolitis. Past studies supporting the use of albuterol did not control for effects of change in state of the infant and did not use a truly inactive placebo group. This study underscores the importance of these design components in measuring the efficacy of albuterol in infants. PMID- 8190576 TI - Which dogs bite? A case-control study of risk factors. AB - OBJECTIVE: Dog bites cause an estimated 585,000 injuries resulting in the need for medical attention yearly and children are the most frequent victims. This study sought to determine dog-specific factors independently associated with a dog biting a nonhousehold member. METHODS: A matched case-control design comprising 178 pairs of dogs was used. Cases were selected from dogs reported to Denver Animal Control in 1991 for a first-bite episode of a nonhousehold member in which the victim received medical treatment. Controls were neighborhood matched dogs with no history of biting a nonhousehold member, selected by modified random-digit dialing based on the first five digits of the case dog owner's phone number. Case and control dog owners were interviewed by telephone. RESULTS: Children aged 12 years and younger were the victims in 51% of cases. Compared with controls, biting dogs were more likely to be German Shepherd (adjusted odds ratio (ORa) = 16.4, 95% confidence interval (CI) 3.8 to 71.4) or Chow Chow (ORa = 4.0, 95% CI 1.2 to 13.7) predominant breeds, male (ORa = 6.2, 95% CI 2.5 to 15.1), unneutered (ORa = 2.6, 95% CI 1.1 to 6.3), residing in a house with > or = 1 children (ORa = 3.5, 95% CI 1.6 to 7.5), and chained while in the yard (ORa = 2.8, 95% CI 1.0 to 8.1). CONCLUSIONS: Pediatricians should advise parents that failure to neuter a dog and selection of male dogs and certain breeds such as German Shepherd and Chow Chow may increase the risk of their dog biting a nonhousehold member, who often may be a child. The potential preventability of this frequent public health problem deserves further attention. PMID- 8190577 TI - Recombinant human erythropoietin in the treatment of the anemia of prematurity: results of a double-blind, placebo-controlled study. AB - OBJECTIVE: To assess the efficacy of recombinant human erythropoietin (rHuEpo) in the treatment of the anemia of prematurity. METHODOLOGY: A double-blind, placebo controlled study was conducted on 80 preterm infants (< or = 32 weeks; postnatal age, 2 to 8 weeks; central hematocrit < or = 35%). Patients were randomly assigned to receive subcutaneous rHuEpo (Eprex, 600 U/kg per week) or an equivalent volume of placebo, for up to 6 weeks. All patients received supplements of vitamin E (25 IU) and iron (3 mg/kg per day). The iron supplement was increased if declining serum ferritin measurements were noted. RESULTS: Treatment and placebo groups did not differ significantly with respect to mean gestational age, birth weight, hematocrit, or reticulocyte count at study entry. Fewer transfusions were administered to those receiving erythropoietin (7 compared with 21; P = .002). Compared with the placebo group, the infants receiving rHuEpo had a higher mean hematocrit (32.3 +/- 4% vs 29.3 +/- 6.2%; P = .014) and absolute reticulocyte count (223 +/- 73 vs 124.9 +/- 73 x 10(9)/L; P < .001) at the end of the study. The mean neutrophil count was not significantly reduced at study exit (P = .8), nor at any other period during the trial in the rHuEpo group. Intercurrent events (mostly infections) were not increased in the treatment group, although there was one case of sudden infant death syndrome at age 4 months. CONCLUSIONS: Using a dose of rHuEpo of 600 U/kg per week, this study has shown a clear reduction in the requirement for blood transfusion in preterm infants. PMID- 8190578 TI - Care of the child with tympanostomy tubes: a visual guide for the pediatrician. PMID- 8190579 TI - Human immunodeficiency virus infection/AIDS in children: the next decade. AB - The next decade of HIV/AIDS must resolve critical issues. It will be necessary to probe deeply to examine what is currently known, identify what needs to be known, and find ways to solve the issues that must be confronted. How to best achieve solutions in a timely manner must also be determined. Seven priorities of major importance have been identified. There are others, and there will be new ones. Each issue is complex, but each one must be faced with the hope that solutions will be found. After 10 years, HIV infection is at risk of becoming institutionalized, bringing with it an acceptance of the issues as inherent to the disease. Patients look to the medical profession and scientific community to provide hope. But there are also significant educational, psychological, social, and public health issues that must be resolved. The first decade of AIDS consisted of recognition, diagnosis, and early treatment. If hope is to be brought to our children and their parents, the next decade must consist of the prevention and therapeutic control of HIV and its complications. PMID- 8190580 TI - Job Lewis Smith and the germ theory of disease. PMID- 8190581 TI - Measles vaccine immunogenicity in 6- versus 15-month-old infants born to mothers in the measles vaccine era. AB - HYPOTHESIS: The low titer of measles antibody in infants of mothers with vaccine induced immunity may allow immunization against measles before 15 months of age. METHODS: Six- and 15-month-old infants born to mothers < or = 30 years of age with no history of measles were recruited. Infants enrolled at 6 months of age were immunized with monovalent measles vaccine (Attenuvax), and maternal serum and infant pre- and postvaccination sera were obtained. Those enrolled for primary vaccination at 15 months of age received either Attenuvax (N = 12) or M-M RII (N = 3). Six-month-old infants were revaccinated with M-M-RII at 15 months of age; pre- and postrevaccination sera were again obtained. Three antibody assays were used: a measles neutralizing assay (NT) and two enzyme immunoassays (EIA) for measles IgG and measles IgM. RESULTS: Among primary vaccinees, 14 of 19 infants aged 6 months (74%) developed NT antibody, as did 15 of 15 infants aged 15 months (100%). The reciprocal geometric mean titer of 6-month-old seroresponders was 23.3, significantly lower than that of the 15-month-old primary vaccinees (87.7, P < .001). Primary seroconversion rates by EIA were 53% for 6-month-old infants and 100% for those aged 15 months. Revaccination of infants who had received Attenuvax at 6 months of age resulted in 100% NT positivity; the geometric mean titer rose to equal that of the group given primary immunization at 15 months of age. Measles IgM antibody was detected in 10 of 14 infants tested 1 month after primary vaccination at 15 months, but was not detected in any of the revaccinated infants after the second dose at 15 months of age (P < .001). CONCLUSIONS: 1) Immunization with measles vaccine in infants born to vaccine-immune mothers at 6 months of age induced NT antibody in 74% of infants. 2) Revaccination of prior 6-month-old vaccinees at 15 months resulted in antibody titers equivalent to 15-month-old vaccinees. 3) Lack of an IgM response following revaccination suggests that even seronegative infants may be primed to respond on re-exposure to measles. PMID- 8190582 TI - Estimating neonatal mortality risk: an analysis of clinicians' judgments. AB - BACKGROUND: Clinicians' estimates of mortality risk in the neonatal intensive care unit (NICU) have implications for patient triage, transfer, initiation and termination of life support, and allocation of medical resources. The accuracy of these judgments has not been studied, nor the differences between nurses and attending physicians. OBJECTIVES: 1) evaluate the accuracy of subjective judgments of NICU unit mortality risk, 2) identify the key components of clinician judgments, 3) compare accuracy between attending physicians and nurses, and 4) examine the utility of combining an objectively computed risk and clinician judgments to improve predictions. METHODS: We obtained estimates of mortality risk on 544 admissions to two NICUs on the day of admission from the attending physician and primary nurse. These were compared with an objective computed mortality risk based on birth weight and the Score for Neonatal Acute Physiology (SNAP) using a linear judgment analysis model, as well as with actual outcomes. RESULTS: Physicians and nurses had good discriminating power with actual mortality rates ranging from 0% among low risk patients to 67% among those with the highest mortality estimates. Physicians had a tendency to overestimate mortality risk. Clinicians base their estimates on the same factors and similar judgment weights as the empiric mortality risk model (22% birth weight, 62% illness severity (SNAP), 13% low Apgar, and 3% for intrauterine growth restriction). Clinicians place additional emphasis on therapeutic as well as physiologic factors. When the computed risk and physician judgment were combined, both made significant contributions in a logistic mortality risk model. CONCLUSIONS: Clinician judgments of mortality risk are fairly accurate and similar to an objective illness severity index. This simple method provides insight into clinical decision making and has important applications in improving direct patient care, appropriate allocation of medical resources, and medical training. PMID- 8190583 TI - Guidelines for medical student education in community-based pediatric offices. American Academy of Pediatrics Council on Pediatric Education Subcommittee on Medical Student Curriculum. AB - The special constellation of knowledge, skills, and attitudes that are necessary to practice general pediatrics should be an integral part of the curriculum of all medical schools. Community-based pediatric educational experiences should be integrated into the medical school curriculum starting in the first year. The curriculum should be developed as a joint undertaking of clerkship directors and community pediatricians. Implementation of the curriculum requires ongoing faculty development to learn to use focused teaching, to establish educational objectives, and to adapt educational experiences to the unique characteristics of the office setting. Methods and techniques for the ongoing evaluation of the students' performance, and evaluating faculty members' abilities to implement an effective educational program must also be developed. PMID- 8190584 TI - Children in car crashes: analysis of data for injury and use of restraints. AB - OBJECTIVE: To determine the effect of car restraints on motor vehicle injury rates for children aged 0 to 14 years. METHODS: A probability sample of all police-reported car crashes in the United States in 1990 and 1991 was analyzed for injury rates of passengers aged less than 15 years in relation to restraint usage, age, and seating position. RESULTS: Optimal restraint usage (defined as car seats for children 0 to 4 years old and lap shoulder belts for children 5 to 14 years old) was 40%. The use of the car seat was 76% for infants (0 to 12 months old) and 41% for toddlers (1 to 4 year olds). The non use of a restraint was highest for 10 to 14 year olds (43%). The rate of involvement in car crashes for all children was 21.4 (per 1000/yr). The highest rate was the 14 year olds with 29.6 followed by 2 year olds with 26.5. Injury rates were 4.76 (per 1000/yr) for all children. The lowest rate was 2.91 for infants but increased to 4.78 for 3 year olds. The single strongest risk factor for injury was the non use of a restraint. (Adjusted odds ratio 2.7; 95% CI 2.4 to 3.0.) The risk factor for injury for the front seat was 1.5 (95% CI 1.4 to 1.7). Use of the car seat reduced injuries by 60% for 0 to 4 year olds, whereas the lap shoulder harness was only 38% effective for 5 to 14 year olds (P < or = .001) Injury rates of unrestrained 0 to 4 and 5 to 14 year olds were similar. CONCLUSIONS: Greater involvement in car crashes and less use of car restraints explains the 64% higher rate of injury for 3 year olds than for infants. It is time to target the toddlers. Restraints designed for adults are not as effective for the school age child as car seats are for the preschool child. A better restraint for the school age child should be designed and evaluated. Meanwhile, increased usage of current restraints must be encouraged, as they substantially reduce injuries. PMID- 8190585 TI - Sexual practices and intentions among preadolescent and early adolescent low income urban African-Americans. AB - OBJECTIVE: To assess the sexual practices and the social and intrapersonal influences on sexual practices and intentions which have an impact on the risk for acquired immunodeficiency syndrome among pre- and early adolescent, low income African-American youths. DESIGN: Cross-sectional cohort study conducted in nine recreation centers serving three public housing developments in an eastern city. PARTICIPANTS: Three hundred fifty-one African-American youths 9 to 15 years of age. OUTCOME MEASURES: Past and intended sexual intercourse, and past and intended condom use determined by a risk assessment instrument delivered aurally and visually via a "talking" MacIntosh computer. RESULTS: The median age was 11 years; 35% of youths had had sexual intercourse and 20% of virgins thought it likely that they would become sexually active in the next six months. Age and male gender were correlated with sexual activity. Of sexually active youths 62% had used a condom during their last episode of coitus and 60% expected to do so at the next episode. Among sexually active youths, 24% of boys and 35% of girls had had anal intercourse. Rates of foreplay (nonpenetrative sex) were low even among sexually active youths. The median number of sexual partners in the past six months was two. Social influences from parents, peers, and partners in an intimate relationship were important for all four sexual outcomes both by univariate analysis and after logistic regression. IMPLICATIONS: A high percentage of the low-income, urban African-American pre- and early adolescents in this study are engaging or intending to engage in high-risk sexual behaviors. Acquired immunodeficiency syndrome reduction interventions for early adolescents should incorporate the importance of social influences from multiple sources. PMID- 8190586 TI - Infant walker-related injuries: a prospective study of severity and incidence. AB - OBJECTIVE: To determine the incidence and significance of walker-related injuries in infants. METHODS: During a 3-year, 8-month period, all infants who were brought to the University of Virginia Pediatric Emergency Department with a walker-related injury were prospectively studied. During the emergency department visit, demographic and epidemiologic information were recorded. The annual incidence of walker-related injuries occurring in infants < 1 year of age that resulted in a hospital emergency department visit was calculated from the home zip codes of the injured patients and from the population of infants < 1 year of age living in Charlottesville and in Albemarle County. RESULTS: Sixty-five patients were enrolled in the study. The age distribution ranged from 3 months to 17 months, with 95% younger < 1 year old. Mechanisms associated with walker related injuries included stairway falls in 46 infants (71%), tip-overs in 14 infants (21%), falls from a porch in 2 infants (3%), and burns in 3 infants (5%). These injuries predominantly involved the head and neck region (97%), with few injuries to the extremities (6%) and trunk (3%). Although the majority of injuries were minor, significant injuries occurred in 19 infants (29%). These injuries included skull fracture, concussion, intracranial hemorrhage, full thickness burns, c-spine fracture, and death. After excluding the burned patients, all the serious injuries resulted from falls down stairs. The annual incidence of injuries occurring in infants < 1 year of age, related to the use of walkers, and resulting in an emergency department visit was 8.9/1000, and for serious injuries was 1.7/1000. CONCLUSIONS: The incidence and significance of infant walker-related injuries in infants are unacceptably high. PMID- 8190587 TI - Risk factors for pneumonia among children in a Brazilian metropolitan area. AB - OBJECTIVE: To investigate risk factors for pneumonia for infants < 2 years of age. DESIGN: Hospital-based, case-control study with neighborhood control subjects. SETTING: Urban area in southern Brazil. SUBJECTS: Five hundred ten infants with radiologically confirmed pneumonia who were admitted to a pediatric hospital. One age-matched neighborhood control subject was selected for each case. RESULTS: Multiple conditional regression modeling was used to control for confounding, taking into account the hierarchical relationships between risk factors. The incidence of radiologically confirmed pneumonia was associated with low paternal education, the number of persons in the household, young maternal age, attendance at day-care centers, low birth weight and weight-for-age, lack of breast-feeding and of non-milk supplements, and a history of previous pneumonia or wheezing. Day-care center attendance showed the highest risk, with an adjusted odds ratio of 11.75. CONCLUSIONS: In addition to continued efforts toward appropriate case management, actions directed against the above risk factors may help prevent the major cause of deaths of children younger than 5 years. PMID- 8190588 TI - Management errors leading to unnecessary hospitalization for kerion. AB - OBJECTIVE: Tinea capitis is a common problem in the inner city, outpatient population. It is known that some children were being admitted for treatment of the kerion type of tinea capitis. The purpose of this study was to determine why these children were being admitted and whether hospitalization was justified. DESIGN: A retrospective study of all children hospitalized at Children's Hospital of Wisconsin between January 1990 and December 1992 with the diagnosis of tinea capitis was performed. RESULTS: Twenty-nine children who were hospitalized with tinea capitis were identified. In 10 cases, tinea capitis was the primary reason for admission, in 19 patients it was a secondary diagnosis. All of the patients with a primary diagnosis of tinea capitis were presumed to have a secondary bacterial infection of the kerion; however, this was not verified by the workup of any patient. Numerous deviations from optimal treatment were noted in both groups of patients. Although tinea capitis had been correctly diagnosed before admission in seven primary tinea capitis patients, only two of these patients received oral griseofulvin. The patients in whom tinea capitis was a secondary diagnosis also had a number of therapeutic deficiencies including failure to prescribe griseofulvin (16%), failure to administer griseofulvin with a fatty food or meal (58%), and failure to prescribe a sporicidal shampoo (63%). CONCLUSIONS: Although all patients were assumed to have a secondary bacterial infection, this could not be documented. With the possible exception of one patient all the symptoms described by the patients could be explained by the highly inflammatory nature of a kerion. A better understanding of the degree of inflammation that may accompany a kerion, as well as its proper treatment, may prevent unnecessary hospitalization of children. PMID- 8190589 TI - Rate of weight gain of inpatients with anorexia nervosa under two behavioral contracts. AB - OBJECTIVE: To ascertain the rate of weight gain of inpatients with anorexia nervosa under two behavioral contracts, differing in criterion weight gain required to earn increasing privileges. DESIGN: Follow-up comparison of cohorts receiving different interventions. SETTING: Eating disorders service, operating on a general adolescent medicine unit. PATIENTS: Patients admitted consecutively who met the following criteria: (1) weight at least 15% less than that expected for age, sex, and height; (2) female gender; (3) absence of chronic medical illness; (4) hospital stay of at least 28 days. Twenty-two patients meeting these criteria were treated between July 1987 and October 1988, when contract 1 was in effect. This cohort of patients was compared with a group of 31 patients, also meeting the these criteria, who were treated between November 1988 and December 1991, when contract 2 was in effect. INTERVENTIONS: The behavioral contract, signed by the patient on admission, specifies the minimum 4-day weight gain necessary to earn increasing ward privileges, such as use of phone, frequency of visits, etc. Contracts 1 and 2 differed only in the 4-day weight gain criterion: 0.8 lb (0.36 kg) and 1.2 lb (0.55 kg), respectively. RESULTS: The results of analysis of covariance, with admission weight as the covariate, revealed a significant interaction between contract and day, such that patients receiving contract 2 gained weight more rapidly (0.36 lb/d) than those receiving contract 1 (0.20 lb/d). There was no confounding difference between groups in the use of psychotropic medication, and no complications of refeeding in either group. CONCLUSION: Increasing the 4-day criterion weight gain from 0.8 to 1.2 lb in a behavioral contracting intervention was associated with a significant increase in the rate of weight gain, without an accompanying increase in complications of refeeding. This result simultaneously: (a) provides support for the efficacy of behavioral contracting and (b) reveals malleability in the rate of gain based on the targeted gain specified in the contract. PMID- 8190590 TI - Do young boys with fragile X syndrome have macroorchidism? AB - OBJECTIVE: Macroorchidism is one of the most well-described clinical characteristics of men with fragile X syndrome, but little information has been available regarding macroorchidism in prepubertal boys with fragile X. The purpose of this study was to learn whether macroorchidism is a characteristic of fragile X syndrome in prepubertal boys. METHODS: Clinical assessments were performed on 73 boys, 2.2 to 10.2 years, in whom fragile X either had been diagnosed or who had been referred for fragile X evaluations because of developmental delays. As part of these assessments, we measured testicular volumes using Prader orchiometer beads to find out if macroorchidism occurs before the onset of puberty. RESULTS: From 2.2 through 7 years, boys with fragile X have significantly larger mean testicular volumes than boys without fragile X, but macroorchidism (> or = 4.0 mL or > or = 2 times normal) only occurred in 1 of 27 boys with fragile X. From 8 to 10 years, all our patients with fragile X had clinically enlarged testicles (> or = 3.75 mL), and 7 of 9 boys with fragile X had macroorchidism (> or = 4.0 mL). The testicular volumes of control subjects were all < or = 3.0 mL. CONCLUSIONS: These findings suggest that macroorchidism occurs in some prepubertal boys with fragile X, but in this series it did not occur until age 6 and usually did not occur until after age 8. PMID- 8190591 TI - Kernicterus in premature infants: current prevalence and relationship to NICHD Phototherapy Study exchange criteria. AB - OBJECTIVE: This study was undertaken to determine the current prevalence of kernicterus in premature neonates and to relate the occurrence of kernicterus to 1) the categorization of the infant as "at risk" by National Institute of Child Health and Human Development (NICHD) Phototherapy Study exchange transfusion criteria, and 2) the clinical management of the infant's hyperbilirubinemia. DESIGN: Retrospective review of postmortem and clinical records. SETTING: Magee Womens Hospital, a University of Pittsburgh Medical Center affiliated hospital with approximately 10,000 deliveries per year and a Level III Neonatal Intensive Care Unit with about 1400 admissions annually. SUBJECTS: All neonates autopsied between January 1, 1984 and June 30, 1993 who were < 34 weeks gestation and who lived at least 48 hours; a total of 81 infants. RESULTS: Three infants had kernicterus resulting in a prevalence rate of 4%. These cases included: 1) a 33 week newborn with nonimmune hydrops and a peak bilirubin of 26 mg/dl; 2) a 25 week newborn with asphyxia, hyaline membrane disease, grade IV intraventricular hemorrhage, necrotizing enterocolitis, meconium peritonitis, sepsis, prolonged acidosis, and a peak bilirubin of 11.3 mg/dl; and 3) a 24-week newborn with asphyxia, hyaline membrane disease, grade III intraventricular hemorrhage, and a peak serum bilirubin of 18.5 mg/dl. Of the remaining 78 infants who did not have kernicterus, peak bilirubin ranged from 3.6 to 22.5 mg/dl and 56% had bilirubin levels greater than that suggested as a criterion for exchange transfusion by NICHD Phototherapy Study guidelines; yet all but three were managed with phototherapy alone. CONCLUSIONS: We conclude that kernicterus is currently an uncommon event in preterm infants, even when bilirubin levels are allowed to rise above those previously thought to place the premature infant at risk. PMID- 8190592 TI - Images. PMID- 8190593 TI - Independent effects of lighting, orientation, and stereopsis on the hollow-face illusion. AB - Three experiments were conducted to investigate factors contributing to the 'hollow face' illusion. A novel method was employed in which the distance from the mask at which the illusion became apparent or disappeared, when retreating or approaching, respectively, was taken as a measure of the strength of the illusion. In all the experiments an effect of direction of observer's movement was found, demonstrating the stability of the initial percept. Upright orientations were compared with inverted ones to investigate if the illusion reflects a bias towards a familiar percept. The direction of lighting was also varied. Independent main effects of orientation and lighting were found to be consistent with preferences both for upright faces and for top lighting. However, inverted faces also produced the illusion to some extent, suggesting a general preference for convexity. The role of stereopsis in resolving the illusion was tested by comparing monocular with binocular viewing conditions. Monocular viewing conditions gave rise to shorter distances, suggesting that the retinal disparities available with binocular viewing are important in disambiguating the illusion at small distances. The results are interpreted within the framework of a 2 1/2-dimensional sketch derived from independent modular processing of visual information. PMID- 8190594 TI - Representational development of direction in motion perception: a fragile process. AB - Response to a change in direction is more rapid if the target moves in a predictable direction before the change than if the pre-change direction is not predictable. However, if the target trajectory is viewed for approximately half a second before the change in direction, the effect of directional predictability disappears. Visual information gathered prior to change in direction is used to construct an increasingly more accurate representation of target trajectory. To study this process, we inject various temporal transients into the trajectory prior to the change in direction. We find that extraction of directional information is interrupted if: (i) motion continues along a constant trajectory, but the target disappears briefly behind an implicit or real occluder, (ii) the target pauses briefly, but remains visible, or (iii) the target changes speed briefly, while continuing to move in the same direction. The theoretical implications for motion perception are discussed. These implications include a framework for understanding interactions between stimulus-derived information and a priori information. PMID- 8190595 TI - Judging rolling wheels: dynamic and kinematic aspects of rotation-translation coupling. AB - Four experiments were carried out to investigate observers' abilities to judge rolling motions. The experiments were designed to assess whether two important aspects of such motions are appreciated: the kinematic coupling of rotation and translation, and the dynamic effects of gravity. Different motion contexts of rolling wheels were created using computer-generated displays. The first experiment involved wheels rolling down an inclined plane. Observers spontaneously appreciated the anomaly of wheels that failed to accelerate, but they were not able to differentiate between different acceleration functions. Moreover, their judgments were almost exclusively based on the translation component of the rolling motion, neglecting the rotation component. In a second experiment it was found that observers could accurately estimate the perimeter of various objects. Thus, their inability to consider rotation information is not attributable to misperceptions of the geometry of wheels. In a third experiment the finding that rolling wheels appear to overrotate was replicated; however, findings from this experiment also showed, together with those from a fourth experiment, that observers are able to make very accurate judgments about translation-rotation coupling in rolling wheels when information is provided about the orientation of the wheel and the texture of the surface on which it rolls. PMID- 8190596 TI - The effects of visual depth and eccentricity on manual bias, induced motion, and vection. AB - The relationship between the effects of visual-surround roll motion on compensatory manual tracking of a central display and the perceptual phenomena of induced motion and vection were investigated. To determine if manual-control biases generated in the direction of surround rotation compensate primarily for the perceived counterrotation of the central display ('induced motion') or the perceived counterrotation of the entire body ('vection'), the depth and eccentricity of the visual surround were varied. In the first experiment, twelve subjects attempted to keep an unstable central display level while viewing rotating visual surrounds in three depth planes: near (approximately 20 cm in front of the central display), coplanar, and far (approximately 21 cm behind the central display). In the second experiment, twelve additional subjects viewed a rotating surround that was presented either in the full visual field (0-110 deg) or in central and peripheral regions of similar width. Manual-control biases and induced motion were shown to be closely related to one another and strongly influenced both by central and by peripheral surround motion at or beyond the plane of fixation. Vection, on the other hand, was shown to be much more dependent on peripheral visual inputs. PMID- 8190597 TI - Attentional effects of adaptation of rotary motion in the plane. AB - The effect of attention on the adaptation effects produced by stimuli rotating in the picture plane was examined in five experiments. In experiment 1, subjects performed a task either on a rotating adapting stimulus or on an irrelevant distractor stimulus. Adaptation of a subsequent ambiguous test stimulus was greater when the adapting stimulus was attended than when the irrelevant stimulus was attended. In experiments 2, 3, and 5, two adapting stimuli were presented, rotating in opposite directions, and subjects attended to one or the other. The direction of rotation of the ambiguous test stimulus depended on which adapting stimulus was attended. In experiment 4, the influence of eye movements in producing adaptation in ambiguous motion displays was determined by contrasting the effects of adaptation produced by dual adaptation stimuli rotating in the same or opposite direction. Adaptation effects were not predicted by eye movement hypotheses. PMID- 8190598 TI - Temporal-order judgment and reaction time to stimuli of different rise times. AB - Point of subjective simultaneity and simple reaction time were compared for stimuli with different rise times. It was found that these measures behave differently. To explain the result it is suggested that in the case of temporal order judgment the subject takes into account not only the stimulus onset but also other events connected with stimulus presentation. PMID- 8190599 TI - How is depth perception affected by long-term wearing of left-right reversing spectacles? AB - The plasticity of binocular depth perception was investigated. Six subjects wore left-right reversing spectacles continuously for 10 or 11 days. On looking through the spectacles, the relation between the direction of physical depth (convex or concave) and the direction of binocular disparity (crossed or uncrossed) was reversed, but other depth cues did not change. When subjects observed stereograms through a haploscope and were asked to judge the direction of perceived depth, the directional relation between perceived depth and disparity was reversed both in the two line-contoured stereograms and in the random-dot stereogram in the middle of the wearing period, but the normal relation often returned late in the wearing period. When subjects observed two objects while wearing the spectacles and were asked which appeared the nearer, veridical depth perception increased as the wearing-time passed. These results indicate that the visual transformation reversing the direction of binocular disparity causes changes both in binocular stereopsis and in processes integrating different depth cues. PMID- 8190600 TI - The familiar-size cue to distance and stereoscopic depth perception. AB - The role of the familiar-size cue to distance in stereoscopic depth perception was examined in two experiments. In experiment 1 subjects judged the depth of a binocularly viewed interval, the far point of which was defined by either a familiar or an unfamiliar object, and in experiment 2 subjects adjusted the depth of the interval so that its extent appeared equal to the length of a vertical reference extent positioned on the surface of the object. Although familiar size influenced depth estimates (experiment 1) it did not influence matching judgments (experiment 2). The findings are discussed with reference to the issue of the nature of the familiar-size effects on judgments of stereoscopic depth. PMID- 8190601 TI - [Distribution and frequency of gastric cancer at the para-cardiac region and fornix]. AB - To clarify the distribution and frequency of gastric cancer in the upper third of the stomach, especially in the para-cardiac region and fornix, we reviewed 634 lesions of all gastric cancers in any location in the University Hospital of Tsukuba University from April 1985 to March 1992. The para-cardiac region was defined as a circular area of 6 cm in diameter around the cardia. We found 56 lesions (8.8%) in the para-cardiac region, almost all of which were concentrated in the distal half of the para-cardiac region, and only three of which (0.47%) were in the fornix. Cancer in the upper third of the stomach tended to occur predominantly in aged male patients, and histologically most of them were classified as having differentiated adenocarcinoma. Since the percentage of advanced cancer at the para-cardiac region was much higher than at any other location, we should be careful to obtain double-contrast images of sufficient quality during the upper gastrointestinal examinations and not to overlook subtle changes in this region during the interpretation of films. PMID- 8190602 TI - [Motion artifacts on chest computed tomogram: full scan versus half scan]. PMID- 8190603 TI - [Comparison between MR imaging and pathological findings of the liver and VX2 carcinoma in rabbits after ethanol injection]. AB - Ethanol injection was performed in the liver and VX2 carcinoma in rabbits and we evaluated changes with time by MR imaging, including dynamic study, and pathological findings. In the liver, the necrotic region was demonstrated as an area of low signal intensity on T1-weighted images and one of high intensity on T2-weighted images. Dynamic study after one and two weeks showed no enhancement in the necrotic region. But after a month, the pathologic analysis revealed growth of abundant fibrous stroma replacing the necrotic region, and progressive, concentric enhancement was seen in the necrotic region on dynamic study. On T1 weighted images obtained after the administration of contrast medium, delayed enhancement suggesting that the necrosis contained tissue with abundant interstitial space was seen. In VX2 carcinoma, the necrosis in the tumor was demonstrated as an iso or high signal intensity area on T1-weighted images and an area of low intensity on T2-weighted images, and did not show enhancement as in the dynamic study of the liver. From the pathological analysis, the presence or absence of space containing water among the necrotic cells was suggested to be responsible for these different findings on T1- and T2-weighted images between the liver and VX2 carcinoma after ethanol injection. PMID- 8190604 TI - [Usefulness of dynamic subtraction CT for intracranial high density lesions]. AB - Dynamic subtraction CT (DSCT) using a high speed Rotate/Rotate CT Scanner (Toshiba Xforce) was performed on 10 patients with intracranial high density lesions such as brain tumors and vascular malformations. In comparison with conventional contrast enhanced CT, the technique of dynamic subtraction CT enabled us to evaluate more clearly the contrast enhancement of high density lesions and to separate more easily the lesions from hematoma and calcification, which are shown as avascular areas. The results suggest that DSCT is a valuable method for evaluating the contrast enhancement of intracranial high density lesions. PMID- 8190605 TI - [Evaluation of multislice dynamic MR imaging of the whole liver]. AB - In 47 patients with liver cirrhosis, we performed dynamic MRI with a multisection FLASH technique that enabled us to obtain 13 T 1-weighted images of the entire liver within a single breath hold. Computed tomographic arterial portography (CTAP), US, CT, angiography (AOG) and MRI (spin echo [SE] and dynamic MRI) were performed in all 47 patients. Except for cyst, hemangioma and metastatic tumor, 104 focal nodules less than 3 cm in diameter were detected. These 104 focal lesions were divided into three groups according to the pattern of CTAP: 69 portal supply negative, 11 portal supply decreased, and 24 portal supply normal. In the portal supply negative group, 63 lesions (91%) were detected by dynamic MRI, which was superior to other modalities (US 77%, CT 41%, AOG 70%, MRI-SE 61%). The superiority of dynamic MRI resulted from its excellent ability to detect liver lesions less than 1 cm in diameter. We confirmed histologically that dynamic MRI had almost the same ability to detect hepatocellular carcinoma (HCC) as CTAP. Dynamic MRI should be clinically useful as a noninvasive examination for the detection of HCC. PMID- 8190606 TI - [Clinical application of expandable metallic stent for intractable benign biliary strictures]. AB - Four patients with benign biliary stricture were treated with expandable metallic stent (EMS). In these patients, conventional dilating methods such as balloon dilatation and/or insertion of a tube stent had been attempted before the application of EMS placement without sufficient effects. Successful insertion of EMS was attained in each case, and led to the removal of the external drainage catheter. During the observation period, no recurrent jaundice was seen. No serious complications related to the placement of EMS occurred. In our experience of only four patients with limited follow-up periods, EMS was expected, but not yet established, to be a useful method for the long-term treatment of benign biliary strictures. We emphasize for the present that EMS should be so positioned as not to interfere with any possible successive treatment including surgical intervention. PMID- 8190607 TI - [The effect of PTA on cerebral vessels in experimental vasospasm: a histopathological study]. AB - Although the percutaneous transluminal angioplasty (PTA) is an useful procedure for the treatment of symptomatic vasospasm after subarachnoid hemorrhage, the morphological changes in spastic intracranial vessels after PTA are not yet clear. The purpose of this study was to evaluate the effects of PTA angiographically and histologically. Chronic cerebral vasospasm was induced by producing a blood clot in the subarachnoid space around the top of internal carotid siphon in Japanese monkey. After angiographic recognition of vasospasm, PTA was carried out with silicone microballoon at 1 atmosphere, 3 times for 10 seconds. Angiography after PTA disclosed significant dilatation at the site of PTA, without any significant dilatation of distal spastic vessels. Papaverine hydrochloride was then infused intra-arterially, which resulted in significant dilatation of distal spastic vessels. Upon histological examination, deformation and some denudation of endothelial cells were noted in the intimal layer. At the site of denudation, attachment of platelets was observed despite generalized heparinization. Internal elastic lamina and the media were also stretched and myocytes were deformed and arranged irregularly. These changes were not uniform all over the vascular walls. We conclude that the prolonged effect of PTA may be caused by mechanical damage of endothelial cells and myocytes, and the nonuniformity of histological changes in vascular wall may be a leading cause of its rupture during PTA. PMID- 8190608 TI - [Self-expandable metallic stent therapy for inferior vena cava obstruction secondary to malignancy: clinical observations]. AB - To evaluate the self-expandable metallic stent therapy for inferior vena caval obstruction (IVCO) secondary to malignant liver tumors, changes in caval pressure, the symptoms and hemobiochemical values were observed. Among 16 IVCO cases with higher caval pressure than 20 cmH2O at the peripheral caval lumen to the stenosis, nine cases consisting of five extracaval compression cases and four intravenous tumor thrombi cases subjected the stent therapy. Other three subjected radiotherapy and the other four cases inactive supportive care. Immediately after the Z-stent implantation, the averaged caval pressure distal to the stenosis decreased from 27.7 +/- 3.5 cmH2O to 14.7 +/- 2.6 cmH2O. One case developed 8 cmH2O increase of right atrial pressure but no lung edema. The urine excretion volume increased after stent. The decrease in caval pressure correlated with the urine volume of the day after the stenting (gamma = 0.83), symptomatic improvements of leg edema (gamma = 0.68), ascites (gamma v 0.51) and scrotal edema (gamma = 0.70). Five cases showed gradual increase in platelet number. All elevated LDH and elevated fibrinogen value decreased. These changes would suggest physiologic benefits of the IVC stent therapy. Compression cases showed better improvements and courses than the thrombi cases. Two thrombi cases endured severe conditions suspected of triggered by the procedure. Conclusively, the stent therapy to the IVC obstruction was thought to effect hemodynamically and hematobiochemically. PMID- 8190609 TI - [CT findings of peripheral atelectasis associated with pleural effusion: in association with the mechanism of rounded atelectasis formation]. AB - The role of pleural effusion in the formation of rounded atelectasis (RA) was evaluated using CT in 159 patients with 210 pleural effusions. The forms of peripheral atelectasis associated with pleural effusion (PA-PE) were classified into five types: type 1: no atelectasis, type 2: flat or crescent type, type 3: convex type, type 4: mass-like type, type 5: consolidation type. Atelectasis (type 2-5) accounted for 78% (164/210) of all lesions. Type 2 was the commonest type of PA-PE, followed by type 5. Types 2 and 5 accounted for 79% (130/164) of all lesions with PA-PE. In most lesions of types 2 and 5, the collapsed pulmonary parenchyma re-expanded following decrease or disappearance of pleural effusion. Types 3 and 4 accounted for only 15% (25/164) and 5% (9/164), respectively. Most lesions of type 4 satisfied the criteria of CT findings of RA. Type 3 was similar to type 4 except for the obtuse angle between the collapsed pulmonary parenchyma and the pleura. As a consequence, it is reasonable to regard type 4 as RA, type 3 as the similar lesion of RA. Most lesions of types 3 and 4 were found in patients with small or moderate inflammatory exudate and pleural thickening, and most of them remained the same type in the follow-up studies. Three lesions of type 3 changed to type 4. This study showed that RA was mainly formed in the patients with inflammatory exudate and thickened pleura, rarely in the patients with transudate. It is concluded that inflammatory pleural effusion plays an important role in the formation of RA formation. PMID- 8190610 TI - [MR lymphography: first application to human]. AB - First clinical trial of MR lymphography is described. The subjects were two normal volunteers. The contrast agent was cideferron, which was an iron colloid. We obtained MR images of the inguinal lymph nodes before and after subcutaneous injection of the agent in the dorsal feet. As a result, the signal intensities on T2 weighted images remarkably decreased at two hours after injection and kept low until three months after. Although pigmentation around the injection site was observed, it was gradually fading within six months. In conclusion, MR lymphography with cideferron can be applied clinically. PMID- 8190611 TI - [A twining method for struts connection in Z-stents]. AB - To compose Gianturco Z-stents without welding, a twining method was applied. The link portion of the struts of were spirally entwined by a thin stainless steel wire of 0.1 mm in diameter. The directional balance of spring force of the twined stents compared favorably with that of the conventionally welded stents. This twining method has theoretical benefit of less susceptible to corrosion than soldering. Then the twining method was thought to be beneficial in composing Z stents. PMID- 8190612 TI - [Economic inducement in health care--what are the lasting effects?]. PMID- 8190613 TI - [Management of health services--financing method tool]. AB - Financing methods for health care have great actuality in the Nordic countries. Incentive theory background is briefly presented. The main categories and subcategories of financing methods are listed. For the global budget solutions capitation and global budget based on historical costs, the advantages and problems are discussed. The two main categories per-case reimbursement, retrospective and prospective, are presented. The retrospective category includes per-diem rates and fee-for-service payment. Prospective reimbursement can be done on the basis of product definitions or episodes of care. The possibility of result grading the per-case reimbursement is mentioned. Problem solving by hybrid methods of financing is presented. Requirements to reimbursement methods can be: 1) They should be clinically neutral or assist in reaching formulated goals. 2) They should not result in unwanted use of any level of care. 3) They should not present barriers to justified referral between any level of care. PMID- 8190614 TI - [Stomach physiology and ulcer drugs]. PMID- 8190615 TI - [Acute confusional states in patients with hip fractures can be prevented and treated]. AB - Acute confusional states among the elderly constitute a manifest problem in most medical specialties. All too often the disoriented patient is deemed to be suffering from dementia, and no investigation is made of the background factors. Intervention studies have clearly shown that confusional states are both reversible and preventable. PMID- 8190616 TI - [Insulin resistance--current findings on background and treatment]. AB - A number of pathological conditions have been associated with increased insulin resistance. Reduced insulin sensitivity may occur even under normal physiological conditions, and is more pronounced in men than in women. The aetiology of type II diabetes, lipid disorders and hypertension is characterised by reduced insulin sensitivity. A new theory which has been advanced to explain these pathological conditions is the occurrence of intra-uterine growth retardation due to fetal malnutrition. The elucidation of these events may affect treatment in the future. PMID- 8190617 TI - [Can glucose be harmful?]. PMID- 8190618 TI - [Backache--current orthopedic viewpoints]. PMID- 8190619 TI - [WHO in former Yugoslavia]. AB - The World Health Organisation (WHO) has been at work in the former Yugoslavia since the summer of 1992. The Scandinavian countries have been very active in the project, and many Scandinavian citizens have been involved. Considerable contributions will be required for a long time to come. The article provides an account of the background to the WHO project and of its organisation, working methods and results. PMID- 8190620 TI - The impact of OSHA, ADA, and the twenty dollar difference. PMID- 8190621 TI - Mutations to nonsense codons in human genetic disease: implications for gene therapy by nonsense suppressor tRNAs. AB - Nonsense suppressor tRNAs have been suggested as potential agents for human somatic gene therapy. Recent work from this laboratory has described significant effects of 3' codon context on the efficiency of human nonsense suppressors. A rapid increase in the number of reports of human diseases caused by nonsense codons, prompted us to determine how the spectrum of mutation to either UAG, UAA or UGA codons and their respective 3' contexts, might effect the efficiency of human suppressor tRNAs employed for purposes of gene therapy. This paper presents a survey of 179 events of mutations to nonsense codons which cause human germline or somatic disease. The analysis revealed a ratio of approximately 1:2:3 for mutation to UAA, UAG and UGA respectively. This pattern is similar, but not identical, to that of naturally occurring stop codons. The 3' contexts of new mutations to stop were also analysed. Once again, the pattern was similar to the contexts surrounding natural termination signals. These results imply there will be little difference in the sensitivity of nonsense mutations and natural stop codons to suppression by nonsense suppressor tRNAs. Analysis of the codons altered by nonsense mutations suggests that efforts to design human UAG suppressor tRNAs charged with Trp, Gln, and Glu; UAA suppressors charged with Gln and Glu, and UGA suppressors which insert Arg, would be an essential step in the development of suppressor tRNAs as agents of human somatic gene therapy. PMID- 8190622 TI - Subtraction hybridisation and shot-gun sequencing: a new approach to identify symbiotic loci. AB - Traditionally, new loci involved in the Rhizobium-legume symbiosis have been identified by transposon mutagenesis and/or complementation. Wide dispersal of the symbiotic loci in Rhizobium species NGR234, as well as the large number of potential host-plants to be screened, greatly reduces the efficiency of these techniques. As an alternate strategy designed to identify new NGR234 genes involved in the early stages of the symbiosis, we combined data from competitive RNA hybridisation, subtractive DNA hybridisation and shot-gun sequencing. On the assumption that the expression of most nodulation genes is triggered by compounds released by the host-plant, we identified, in the ordered cosmid library of the large symbiotic plasmid pNGR234a, restriction fragments that carry transcripts induced by flavonoids. To target genes not present in the closely related strain R. fredii USDA257, we selected fragments that also carried sequences purified by subtractive DNA hybridisation. Shot-gun sequencing of this subset of fragments lead to the identification of sequences with strong homology to diverse prokaryotic genes/proteins. Amongst these, a symbiotically active ORF from pNGR234a, is highly homologous to the leucine responsive regulatory protein of Escherichia coli (Lrp), is induced by flavonoids, and is not present in USDA257. PMID- 8190623 TI - DNA sequence specificity of mitoxantrone. AB - An in vitro transcription assay was used to determine the sequence specificity of binding of mitoxantrone to a 497 bp fragment of DNA containing the lac UV5 promoter. Transcriptional blockages of the E. coli RNA polymerase were observed dominantly prior to 5'-CpA sequences (64% occurrence), and to a lesser extent 5' CpG sequences (29%). Overall, 93% of all blockage sites were prior to pyrimidine (3'-5') purine sequences. An effect of flanking sequences was evident since the blockage sites contained an A/T base pair 5' prior to the consensus CpA and CpG intercalation sites. The consensus sequences for the preferred mitoxantrone intercalation sites are therefore 5'-(A/T)CA and 5'-(A/T)CG. The location of transcriptional blockages one base pair prior to the intercalation site is consistent with the fact that the mitoxantrone side chains lie in the major groove. PMID- 8190624 TI - The 3'-untranslated region of alfalfa mosaic virus RNA 3 contains at least two independent binding sites for viral coat protein. AB - The 3'-termini of the three genomic RNAs of alfalfa mosaic virus contain a common sequence of 145 nucleotides (nt) with a specific binding site for coat protein (CP). This sequence consists of several stem/loop structures interspersed with single-stranded AUGC-motifs; in RNA 3 this folding pattern is extended to a region upstream of the homologous sequence. By band-shift assays a minimum of two specific binding sites for CP were identified near the 3'-end of RNA 3. Site 1 consists of the region between nt 11 and 127 from the 3'-end and contains two AUGC-motifs. Site 2 is located between nt 133 and 208 from the 3'-end in a sequence that is largely unique to RNA 3 and contains also two AUGC-motifs. Deletion studies revealed that the two sites could bind CP independently of each other and permitted the identification of sequence elements that are essential for the activity of each site. By site-directed mutagenesis it was shown that the AUGC-motifs are important for binding of CP to both sites. These binding sites may play a role in the phenomenon that each genomic RNA has to be complexed with a few CP molecules to initiate infection. Later in the replication cycle they may act as origins for the assembly of virus particles. PMID- 8190625 TI - Control of polyadenylation and alternative splicing of transcripts from adjacent genes in a procyclin expression site: a dual role for polypyrimidine tracts in trypanosomes? AB - The procyclin-associated genes (PAGs) of Trypanosoma brucei are located downstream of tandemly repeated procyclin genes and belong to the same alpha amanitin-resistant polycistronic transcription units. In procyclic form trypanosomes the PAG 1 pre-mRNA is alternatively spliced to give rise to three transcripts of 2.7 kb, 1.8 kb and 1.3 kb. The two larger transcripts contain additional short open reading frames (ORFs) upstream of the major ORF. Trans splicing to generate these transcripts occurs downstream of three different polypyrimidine tracts. A minor population of procyclin mRNAs is also generated by alternative splicing at a polypyrimidine tract that begins 524 bp upstream of the major splice acceptor site of the procyclin beta-gene. The same polypyrimidine tract is also required for accurate polyadenylation of mRNAs from the upstream procyclin alpha-gene (1). Alternatively polyadenylated forms of PAG 1 mRNAs can also be detected. All polyadenylation sites are found at a similar distance upstream of splice-acceptor sites, in each case with a polypyrimidine tract between them. Our results point to a dual role for polypyrimidine tracts in the maturation of trypanosome mRNAs. PMID- 8190626 TI - Studies of oligonucleotide interactions by hybridisation to arrays: the influence of dangling ends on duplex yield. AB - Effects of dangling ends on duplex yield have been assessed by hybridisation of oligonucleotides to an array of oligonucleotides synthesised on the surface of a solid support. The array consists of decanucleotides and shorter sequences. One of the decanucleotides in the array was fully complementary to the decanucleotide used as solution target. Others were complementary over seven to nine bases, with overhangs of one to three bases. Duplexes involving different decanucleotides had different overhangs at the 3' and 5' ends. Some duplexes involving shorter oligonucleotides had the same regions of complementarity as these decanucleotides, but with fewer overhanging bases. This analysis allows simultaneous assessment of the effects of differing bases at both 5' and 3' ends of the oligonucleotide in duplexes formed under identical reaction conditions. The results indicate that a 5' overhang is more stabilising than a 3' overhang, which is consistent with previous results obtained with DNA overhangs. However, it is not clear whether this is due to the orientation of the overhang or to the effect of specific bases. PMID- 8190628 TI - P2 functions as a spacer in the Tetrahymena ribozyme. AB - The function of the P2 stem-loop region in the group I catalytic intron from Tetrahymena thermophila has been investigated. A comprehensive mutation analysis suggests that the bottom base pair of the P2 stem and nucleotides in the loop L2 are involved in interactions elsewhere on the intron. In addition, the P2 stem can be varied only between 9 and 11 base pairs in length. Phylogenetic evidence (3) from a sub-class of group I introns supports a model in which the P1 and P2 stems are coaxially stacked. We found that variation of the length of P2 does not shift the sites of intron-catalyzed cleavage in P1 (9). This suggests that coaxial stacking of the P1 and P2 stems is unlikely in the Tetrahymena intron. A narrowing of the window for cleavage activity and a drop in cleavage efficiency are observed when substrates with an insertion in P2 are compared with those with a deletion. A possible explanation for this phenomenon is an unfavorable movement of P1 away from the active site as a result of the the lengthening of P2. PMID- 8190627 TI - Probing the structure of mouse Ehrlich ascites cell 5.8S, 18S and 28S ribosomal RNA in situ. AB - The secondary structure of mouse Ehrlich ascites 18S, 5.8S and 28S ribosomal RNA in situ was investigated by chemical modification using dimethyl sulphate and 1 cyclohexyl-3-(morpholinoethyl) carbodiimide metho-p-toluene sulphonate. These reagents specifically modify unpaired bases in the RNA. The reactive bases were localized by primer extension followed by gel electrophoresis. The three rRNA species were equally accessible for modification i.e. approximately 10% of the nucleotides were reactive. The experimental data support the theoretical secondary structure models proposed for 18S and 5.8/28S rRNA as almost all modified bases were located in putative single-strand regions of the rRNAs or in helical regions that could be expected to undergo dynamic breathing. However, deviations from the suggested models were found in both 18S and 28S rRNA. In 18S rRNA some putative helices in the 5'-domain were extensively modified by the single-strand specific reagents as was one of the suggested helices in domain III of 28S rRNA. Of the four eukaryote specific expansion segments present in mouse Ehrlich ascites cell 28S rRNA, segments I and III were only partly available for modification while segments II and IV showed average to high modification. PMID- 8190629 TI - Antibodies generated from human immunoglobulin miniloci in transgenic mice. AB - One approach to the production of human monoclonal antibodies focusses on the creation of transgenic mice bearing human immunoglobulin gene miniloci. Whilst such loci undergo lymphoid-specific gene rearrangement, only a small proportion of mouse B cells express the human immunoglobulin chains; the miniloci thus contribute poorly to serum immunoglobulin. Attributing this poor performance to competition between the transgenic and endogenous immunoglobulin loci, we crossed mice bearing a human immunoglobulin heavy-chain (HulgH) minilocus with animals that had been rendered B cell-deficient by disruption of their endogenous heavy chain locus. The results were dramatic: the human minilocus rescued B cell differentiation such that effectively all B cells now expressed human mu chains. The concentration of antibody in the mouse serum recognised by anti-human mu increased to a concentration about one sixth that in human serum. The HulgH antibodies are heterogenous with diversity being generated by both combinatorial and junctional processes. Following antigen challenge, specific antibody is elicited but at low titre. PMID- 8190630 TI - Contacts between the growing peptide chain and the 23S RNA in the 50S ribosomal subunit. AB - Peptides of defined length carrying a diazirine photoaffinity label attached either to the alpha-NH2 group of the N-terminal methionine residue, or to the epsilon-NH2 group of an immediately adjacent lysine residue, were prepared in situ on Escherichia coli ribosomes in the presence of a synthetic mRNA analogue. Peptide growth was stopped simply by withholding the aminoacyl-tRNA cognate to an appropriate downstream codon. After photo-activation at 350 nm the sites of cross linking to ribosomal RNA were determined by our standard procedures; the C terminal amino acid of each peptide was labelled with tritium, in order to confirm whether the individual cross-linked complexes contained the expected 'full-length' peptide, as opposed to shorter products. The shortest peptides became cross-linked to sites within the 'peptidyl transferase ring' of the 23S RNA, namely to positions 2062, 2506, 2585 and 2609. However, already when the peptide was three or four residues long, a new cross-link was observed several hundred nucleotides away in another secondary structural domain; this site, at position 1781, lies within one of several RNA regions which have been implicated in other studies as being located close to the peptidyl transferase ring. Further application of this approach, combined with model-building studies, should enable the path of the nascent peptide through the large ribosomal subunit to be definitively mapped. PMID- 8190631 TI - Nucleotide sequence of the cox3 gene from Chondrus crispus: evidence that UGA encodes tryptophan and evolutionary implications. AB - We present the nucleotide sequence of the gene encoding subunit 3 of cytochrome c oxidase in Chondrus crispus, the first report on a mitochondrial gene from a red alga. Amino acid alignment with homologous proteins shows that tryptophan is specified by UGA, as in the mitochondrial code of most organisms other than green plants. However, phylogenetic analyses of cox3 amino acid and nucleotide sequences indicate that C. crispus COX3 is related to the green-plant mitochondrial lineage. No RNA editing was detected on the corresponding transcript. As the only known photosynthetic eukaryotes that both share an immediate mitochondrial ancestor with green plants and exhibit features characteristic of non-plant mitochondria, ie, a small-sized mitochondrial genome and a modified genetic code, rhodophytes may be thought of as an intermediate evolutionary link at the root of the green-plant mitochondrial lineage. PMID- 8190632 TI - The differences in the T2 relaxation rates of the protons in the partially deuteriated and fully protonated sugar residues in a large oligo-DNA ('NMR window') gives complementary structural information. AB - Selective incorporation of the stereospecifically deuteriated sugar moieties (> 97 atom % 2H enhancements at H2', H2'', H3' and H5'/5'' sites, approximately 85 atom % 2H enhancement at H4' and approximately 20 atom % 2H enhancement at H1') in DNA and RNA by the 'NMR-window' approach has been shown to solve the problem of the resonance overlap [refs. 1, 2 & 3]. Such specific deuterium labelling gives much improved resolution and sensitivity of the residual sugar proton (i.e. H1' or H4') vicinal to the deuteriated centers (ref. 3). The T2 relaxation time of the residual protons also increases considerably in the partially-deuteriated (shown by underline) sugar residues in dinucleotides [d(CpG), d(GpC), d(ApT), d(TpA)], trinucleotide r(A2'p5'A2'p5'A) and 20-mer DNA duplex 5'd(C1G2C3 G4C5G6C7G8A9A10T11T12C13G14C15G16C17G18C19G20)(2) 3'. The protons with shorter T2 can be filtered away using a number of different NMR experiments such as ROESY, MINSY or HAL. The NOE intensity of the cross-peaks in these experiments includes only straight pathway from H1' to aromatic proton (i-i and i-i + 1) without any spin-diffusion. The volumes of these NOE cross-peaks could be measured with high accuracy as their intensity is 3 to 4 times larger than the corresponding peaks in the fully protonated residues in the normal NOESY spectra. The structural informations thus obtainable from the residual protons in the partially deuteriated part of the duplex and the fully protonated part in the 'NMR window' can indeed complement each other. PMID- 8190633 TI - The genomic structure of the human AP-2 transcription factor. AB - The transcription factor AP-2 is encoded by a gene located on chromosome 6 near the HLA locus. Here we describe the genomic organization of the AP-2 gene including an initial characterization of the promoter. We have mapped two mRNA initiation sites, the entire exon-intron structure and located two polyadenylation sites. The mature AP-2 mRNA is spliced from 7 exons distributed over a region of 18 kb genomic DNA. A recently cloned inhibitory AP-2 protein is generated by alternative usage of a C-terminal exon. The proline-rich transactivation motif is encoded by a single exon within the N-terminal region in contrast to the complex DNA binding and dimerization motif which involves amino acid residues located on four different exons. The sites of mRNA initiation are located 220 and 271 bases upstream from the ATG translation start site. Although the promoter contains no canonical sequence motifs for basal transcription factors, such as TATA-, CCAAT- or SP-1 boxes, it mediates cell-type-specific expression of a CAT reporter gene in PA-1 human teratocarcinoma cells and is inactive in murine F9 teratocarcinoma cells. We demonstrate that the promoter of the AP-2 gene is subject to positive autoregulation by its own gene product. A consensus AP-2 binding site is located at position -622 with respect to the ATG. This site binds specifically to bacterially expressed AP-2 as well as to multiple proteins, including AP-2, present in PA-1 and HeLa cell nuclear extracts. A partial AP-2 promoter fragment including the AP-2 consensus binding site is approximately 5-fold transactivated by cotransfection of an AP-2 expression plasmid. PMID- 8190635 TI - Synthesis of oligodeoxynucleotides containing 2-thiopyrimidine residues--a new protection scheme. AB - A method is described for the incorporation of 2'-deoxy-2-thiouridine (dS2U) and 2'-deoxy-2-thiothymidine (dS2T) into oligodeoxynucleotides at predetermined positions. This requires N3 or O4-acylation of dS2U and dS2T with toluoyl chloride. These base-protected thiopyrimidines are completely stable toward the aqueous iodine oxidation reagent used in the phosphoramidite DNA synthesis method. The toluoyl protecting group is removed during the standard post synthetic ammonia treatment. This novel protection strategy allows dS2U and dS2T to be efficiently incorporated into oligodeoxynucleotides at predetermined sites without the usual problem of desulfurization and decomposition. Several 14-mers containing the Eco-RI recognition site (dGGCGGAAXXCCGCC and dGGCGGAAXXCGCGG, where X represents dT, dS2U or dS2T) have been synthesized and characterized by base composition, thermal denaturation, CD spectroscopy and endonuclease substrate activity. PMID- 8190634 TI - Isolation and characterization of two replication-dependent mouse H1 histone genes. AB - Mice contain at least seven nonallelic forms of the H1 histones, including the somatic variants H1a-e and less closely related variants H1 degrees and H1t. The mouse H1 degrees and H1c (H1var.1) genes were isolated and characterized previously. We have now isolated, sequenced and studied the expression properties of two additional mouse H1 genes, termed H1var.2 and H1var.3. Extensive amino acid and nucleotide sequence comparisons were made between the two genes and other mammalian H1 histone genes. A high degree of nucleotide sequence identity was seen between the H1var.2, rat H1d and human H1b genes, even well beyond the coding region, indicating that these genes are likely homologues. Unlike the previously characterized mouse H1var.1 gene which produces both nonpolyadenylated and polyadenylated mRNAs, the H1var.2 and H1var.3 genes produce only typical, replication dependent, nonpolyadenylated mRNAs. PMID- 8190636 TI - A simple in vivo footprinting method to examine DNA-protein interactions over the yeast PYK UAS element. AB - In this report a modification to the in vivo footprinting assay is described. The method includes dimethyl sulfate treatment of whole yeast cells, followed by reiterative primer extension of the methylated genomic DNA using Taq DNA polymerase. Under appropriate reaction conditions chain extension terminates opposite a methylated purine when Taq DNA polymerase encounters a modified adenine or guanine. The procedure was used to examine, in vivo DNA-protein contacts over the upstream activation site (UAS) of the Saccharomyces cerevisiae PYK gene. In vivo analysis, using isogenic strains of yeast and Escherichia coli transformed with plasmid DNAs, confirmed the binding of both the trans-acting factor RAP1 and the transcriptional activator GCR1 to cis-acting recognition sites located within the PYK UAS element. PMID- 8190637 TI - Purification of a calcium dependent ribonuclease from Xenopus laevis. AB - We have purified a Ca2+ dependent ribonuclease from the oocytes of Xenopus leavis. Two properties of this ribonuclease set it apart from other known nucleases. First, Ca2+ was required for ribonuclease activity, and Mg2+ would not substitute. Second, the enzyme specifically degraded RNA and digestion of double or single stranded DNA was not observed. Ca2+ dependent ribonuclease activity of the purified 36-kDa protein was directly observed after renaturation of the protein following electrophoresis in an SDS-Laemmli gel. In addition, the enzyme was shown to have endoribonuclease activity at numerous sites. The Ca2+ dependence suggests that the ribonuclease activity may be modulated by changes in the level of intracellular Ca2+ and thereby provide a direct link to signal transduction systems. PMID- 8190638 TI - Different binding specificities and transactivation of variant CRE's by CREB complexes. AB - The DNA binding specificities of CREB1 and CREB2 homodimers and the CREB2/cJun heterodimer were analyzed with a CASTing technique. All but one of the selected sequences varied from the consensus CRE (TGACGTCA) by three nucleotides or less. The profile of variations selected and the binding affinity for these sequences were unique for each CREB complex. The affinities were not effected by the palindromic nature of the sequences, but were strongly effected by flanking sequences. The strength of DNA binding in vitro correlated with the degree of transactivation observed in JEG-3 cells transfected with reporter plasmids harboring CRE variants, when hybrid CREB proteins fused to the VP16 activation domain were expressed. When native CREB proteins were expressed, the correlation was attenuated by the nature of the variant sequence. A CRE variant (TGACATCA) found in several natural promoters, exhibited the lowest basal transcription rate of the variants and a lower level of induction than expected when compared with the in vitro binding data. These results indicate that transactivation of DNA sequence elements is strongly effected by the strength of transcription factor binding, and that individual sequences can attenuate the level of induction. PMID- 8190639 TI - Restriction generated oligonucleotides utilizing the two base recognition endonuclease CviJI*. AB - The conversion of an anonymous DNA sample into numerous oligonucleotides is enzymatically feasible using an unusual restriction endonuclease, CviJI. Depending on reaction conditions, CviJI is capable of digesting DNA at a two or three base recognition sequence. CviJI normally cleaves RGCY sites between the G and C to leave blunt ends. Under 'relaxed' conditions CviJI* cleaves RGCY, and RGCR/YGCY, but not YGCR sites. In theory, CviJI* restriction of pUC19 (2686 bp) should produce 157 fragments, 75% of which are smaller than 20 bp. Instead, 96% of the CviJI* fragments were 18-56 bp long and none of the fragments were smaller than 18 bp. Thermal denaturation of these fragments generates sequence specific oligonucleotides homologous for the cognate template. The enzymatic conversion of anonymous DNA into sequence specific oligomers has implications for several conventional and novel molecular biology procedures. PMID- 8190640 TI - Physical map and set of overlapping cosmid clones representing the genome of the archaeon Halobacterium sp. GRB. AB - We have constructed a complete, five-enzyme restriction map of the genome of the archaeon Halobacterium sp. GRB, based on a set of 84 overlapping cosmid clones. Fewer than 30 kbp, in three gaps, remain uncloned. The genome consists of five replicons: a chromosome (2038 kbp) and four plasmids (305, 90, 37, and 1.8 kbp). The genome of Halobacterium sp. GRB is similar in style to other halobacterial genomes by being partitioned among multiple replicons and by being mosaic in terms of nucleotide composition. It is unlike other halobacterial genomes, however, in lacking multicopy families of insertion sequences. PMID- 8190641 TI - Retrotransposition of a marked Drosophila line-like I element in cells in culture. AB - We have marked a Drosophila transposable element--the LINE-like I element--with an intron-containing indicator gene inserted in place of a large deletion in the I element second ORF encompassing the reverse transcriptase domain, and this marked element was placed downstream to a potent actin promoter. An expression vector for the I element ORFs was also constructed, under the same heterologous promoter. The indicator gene contains a lacZ reporter gene the expression of which is conditioned by retrotransposition of the marked element, thus allowing detection of transposition events by testing for either beta-galactosidase expression or occurrence of spliced DNA molecules. The marked I element was introduced into Drosophila melanogaster cells in culture by transfection. Spliced DNA copies of the marked element and specifically stained beta-galactosidase expressing cells were detected only upon co-transfection with the I expression vector, thus indicating that an ORF2-deleted element can be complemented in trans for transposition. This simple assay for retrotransposition in Drosophila cells in culture provides a tool for the rapid analysis of the mechanism of I transposition in its cis and trans sequence requirements. PMID- 8190642 TI - The activation region of the Tat protein of human immunodeficiency virus type-1 functions in yeast. AB - The N-terminal 48 amino acids of the Tat protein of human immunodeficiency virus type (HIV)-1 constitute its activation region. This region can autonomously activate transcription when targeted to the HIV-1 long terminal repeat or certain heterologous promoters either through DNA binding sites located upstream of the transcription initiation site or via downstream RNA binding sites in mammalian cells. To determine whether the Tat activation region can function in yeast, we have assayed the effect of a chimeric gene (GAL-Tat48) expressing the DNA binding domain of the yeast transcription factor Gal4 (residues 1-147) and the activation region of Tat on GAL1 promoter-directed expression of the lacZ reporter gene in Saccharomyces cerevisiae. Our results indicate that the Gal-Tat48 fusion protein can induce significant activation of the GAL1 promoter. Analysis of a number of Tat mutants located within the activation region indicate that the amino acid residues of Tat essential for trans-activation in mammalian cells are also required for transactivation in yeast. Our results suggest that Tat-mediated transcriptional activation may involve a mechanism conserved among yeast and mammalian cells. PMID- 8190643 TI - Definition of a consensus DNA binding site for SRY. PMID- 8190644 TI - Construction of an improved host strain for two hybrid screening. PMID- 8190645 TI - Hyperinducible human metallothionein promoter with a low level basal activity. PMID- 8190646 TI - Molecular tweezers: formation and resolution of plasmid cointegrates as a means of manipulating DNA fragments in vitro. PMID- 8190647 TI - One step DNA sequencing of single-stranded DNA with reverse dye-primer. PMID- 8190648 TI - Direct plasmid shuttling from yeast into Escherichia coli by electroduction. PMID- 8190649 TI - Solid phase DNase I footprinting: quick and versatile. PMID- 8190650 TI - [Selected elements of biological activity of circulating immune complexes in serum of patients with atopic diseases. I. Ability to injure guinea pig tissue by injecting atopic patient plasma]. AB - Serum level was measured of circulating complexes (SpA binding method-CIC/SpA) in pollen and house dust mite sensitive patients during specific immunotherapy. Histopathological changes in guinea pigs skin after the intradermal injection of patients serum have been studied. Differences were demonstrated in the observed patho-morphological changes in relation to CICs/SpA serum concentrations. PMID- 8190651 TI - [Effect of cigarette smoking on carbohydrate metabolism of healthy subjects]. AB - Serum levels of triglycerides (TG), cholesterol (CH), total lipids (LP), beta lipoproteids (B-LP), basal glucose and immunoreactive insulin were assessed in 23 healthy subjects (12 non-smokers and 11 smokers). Influence of smoking cigarettes on level of glycemia and insulin secretion in basal conditions and 30, 60, 90 and 120 minutes after load of 75 g glucose. Concentration of glucose was measured by an enzymatic method and level of IRI by radioimmunoassay. Smokers differed from non-smokers in significantly higher diastolic blood pressure and non significantly higher concentration of TG, CH, LP, B-LP. No statistically significant difference in basal glucose level and profile of glycemia were found between both groups. Significantly higher basal level of insulinemia and increased secretion of insulin after an oral glucose tolerance test were observed in comparison with non-smokers. CONCLUSIONS: 1) The significant higher level of serum basal IRI was found in smokers when compared to non-smokers. 2) Results suggest non-effective hyperinsulinemia in people smoking cigarettes. PMID- 8190652 TI - [The use of a computer program to study gallbladder motor function]. AB - Gallbladder motility was studied in 30 women by means of an ultrasonographic method. Gallbladder volume was examined during intravenous infusion of ceruletide (15 ng Takus/min in 0.9% NaCl solution). It was several dozen less than the dose given intramuscularly. The volume and ejection fraction were defined by the ellipsoid Dodds method in the computer programme Cardio 500. During the infusion of ceruletide it was possible to identify exactly the dose of the drug in every moment and to correlate it with the gallbladder volume. Contour's analysis in Simpson's method made possible to evaluate the contractility of individual parts of the gallbladder. PMID- 8190653 TI - [Acquired cystic kidney disease--etiopathogenesis and clinic]. PMID- 8190654 TI - [Renal hypomagnesemia]. PMID- 8190655 TI - [Enalapril in treatment of severe heart failure in patients with dilated cardiomyopathy]. AB - The study group included 30 middle-aged patients (mean = 47.0 +/- 0.6 years) with chronic heart failure (NYHA class III and IV) in the course of primary dilated cardiomyopathy and ischemic heart disease. Enalapril in a dose of 5-10 mg/day was added to previous therapy with digitalis and diuretics. The patients were submitted for noninvasive cardiac and biochemical studies initially and at 3 months. Twenty-four patients completed the planned therapy. In 5 patients the drug had been withdrawn due to hypotension, and one patient died on the fourteenth day of observation because of heart failure worsening. After enalapril therapy 18 patients improved in NYHA functional classes. All patients showed left ventricular improvement based upon left ventricular systolic time intervals, 18 patients showed reduced peripheral vascular resistance, and in 9 patients echocardiography revealed a significant improvement of EF, CI and mVCF. Renal function also improved based upon the decrease in urea and uric acid. PMID- 8190656 TI - [Long term observations of patients after percutaneous inferior vena cava filter placement for recurrent pulmonary embolism]. AB - Pulmonary embolism remains an important cause of mortality despite recent advances in medical therapy. The inferior vena cava filter has been devised for treatment of pulmonary embolism. The Gunter inferior vena cava filter was inserted percutaneously in 6 patients with recurrent pulmonary embolism despite anticoagulation therapy. No complications were observed during this procedure. Two patients died after filter placement (one after six weeks one after 1.5 year) because of right heart failure observed before procedure. The other four patients showed no signs of pulmonary embolism during four years follow-up. We conclude that percutaneous insertion of the Gunter filter is a safe and effective technique for prevention of recurrent pulmonary embolism. PMID- 8190657 TI - [Body structure and ABO and Rh blood groups in patients with advanced coronary heart disease after aorto-coronary by-pass surgery]. AB - A clinical analysis of the anthropometric traits related to body structure, ABO and rhesus blood groups was performed in 200 male individuals coming mainly from Warsaw and its territorial district. All patients were aged from thirty-one to sixty-eight years (X = 42.3) and total duration of coronary heart disease was from 1 to 12 years. The number of 54 patients (21%) was subjected to surgery because of coronary insufficiency, but without myocardial infarction (M.I.). One or three single cases of M.I. were reported in the remaining number of 146 patients (73%). A degree of extension of arteriosclerotic lesions either in two or three coronary arteries was larger determined upon coronarography. The control group for blood--groups in 200 patients was made of 11,820 healthy male--blood from District Blood Donor Station in Warsaw, but for the anthropometric tracts (height, body weight and Rohrer's index) the control group was made of 283 men aged 35-80 years (average 43.2) coming mainly from Warsaw and its district. Patients after aorto-coronary by-pas surgery with highly advanced arteriosclerosis of the coronary arteries featured indicated significantly higher number of cases with group AB (p < 0.01) due to deficiency in group O (p < 0.05). It has also been found that the occurrence of rhesus blood group lack in patients having undergone by-pass surgery is significantly common (p < 0.01). No significant difference in anthropological traits between the patients after aorto coronary by-pass surgery and the control group from the same geographical region was reported.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190658 TI - [Spleen rupture and ischemic cerebral stroke in a patient with recent myocardial infarction]. AB - A case is presented of recent anterior myocardial infarction in 40-year-old man, treated in acute stage with streptokinase and heparin, complicated by spleen rupture and splenectomy on the 6th day of infarction and by ischemic cerebral stroke on the 15th day. After 10-weeks of therapy patient left the hospital in good clinical condition, which continued 6 months of out-patient follow-up. Results of our examinations excluded haematologic proliferative diseases as a cause of spleen rupture. Fever and recurring pains in the left hypochondrium occurring before infarction suggested possibility of infectious diseases with spleen involvement. In histopathological examination the spleen swelling (as a reaction on an infection) was found. The influence of fibrinolytic and anticoagulant therapy on spleen rupture was discussed. In pathogenesis of ischemic stroke, the thrombocythemia observed after splenectomy and platelet hyperactivity following thrombolytic therapy were taken into consideration. PMID- 8190659 TI - [Evaluation of the efficiency of gemfibrozil in treating hyperlipidemia type IIb and IV]. AB - Analysis of the efficacy and tolerability of gemfibrozil (Gevilon-Parke Davis) was performed including 29 patients aged 19-69 years with primary hyperlipoproteinemia (HLP) type IIb-16 persons, IV-13 persons. All patients got dietary recommendations and received gemfibrozil 450-900 mg/day for 3 months. In both types of HLP a significant reduction of serum cholesterol (TCh)--15.5% triglycerides (TG)--32.1% VLDL-Ch--34.9% and VLDL-TG concentration--36.6% was observed as well as an increase of HDL3 fraction-16.3%. The greatest reduction of serum TCh concentration and VLDL-Ch were observed in type IIb, while that of TG and VLDL-TG in type IV HLP. The best therapeutic effect was obtained during the first month of treatment. The percent of TCh, TG, VLDL-Ch, VLDL-TG reduction correlated with their initial level. Tolerability of gemfibrozil was very good. Only in 2 patients transient abdominal pain was observed. PMID- 8190660 TI - Pathology of neurologic disease in AIDS. AB - The brain is a frequent target of damage in AIDS. In addition to abundant opportunistic infections, HIV itself can cause CNS destruction. Numerous important clinical questions await a basic understanding of the pathogenesis of HIV-associated nervous system destruction. Why does HIV, like many other retroviruses, attack the CNS? How does it get into the CNS, and once it is there, what controls viral replication? What is the mechanism(s) by which HIV mediates CNS damage, and how soon after infection is this process initiated? In the next few years, there will be a rapid convergence of multiple approaches to understanding the pathogenesis of HIV damage in the brain. What clinicians learn will not only aid those patients afflicted with AIDS, but very likely will provide insights into numerous other mysterious and potentially retrovirus mediated brain diseases. PMID- 8190661 TI - Neuropsychological evaluation of the HIV patient. AB - The design of a neuropsychological evaluation of the HIV patient must follow the standard procedures used in any clinical condition. A wide range of cognitive functions should be evaluated to develop a pattern of strengths and weaknesses. Specific attention should be devoted to areas that have been reported to be affected in HIV. However, because concomitant opportunistic infections of the central nervous system are common, evaluation cannot be limited to only these areas. Finally, the special challenge of evaluating people for whom the normative base is limited, including groups such as minorities and drug users, must be kept in mind. PMID- 8190662 TI - Psychotherapies for the person with HIV disease. AB - Work with patients with HIV infections demands the highest degree of professional skill, empathy, and self-understanding on the part of the therapist. He or she must be an excellent diagnostician, must be knowledgeable about the use of medications in a wide array of clinical conditions, and must be willing to confront both psychodynamic issues of the past and realistic medical and social concerns of the present and future. The therapy must be driven not by the disease but informed by the evolving needs, of the individual patient for self understanding and a sense of enhancing competence. Although decline and death must be confronted during therapy, its center is on living and creating an engaged quality of life "in spite of". To help a person find the sweet-tasting strawberry of life in the face of what would otherwise be an intolerable situation can be one of the most meaningful acts we engage in as therapists. PMID- 8190663 TI - Psychological impact of HIV disease and implications for intervention. AB - The stress associated with HIV infection and the psychological impact of that stress have been documented. The complex issues that HIV-positive individuals encounter in managing their disease were described. The existing research on behavioral interventions designed to provide strategies to assist HIV-positive individuals cope with their disease was reviewed, and one particularly cognitive behavioral intervention (Coping Effectiveness Training) was outlined. Given the evidence of the psychological distress that can accompany HIV disease and the consequences that accrue from this distress in terms of delayed access to care, nonadherence to treatment regimens, and quality of life, recommendations were made for health professionals interested in intervening to assist those who are living with the complex challenges of HIV disease. PMID- 8190664 TI - Natural history of neuropsychiatric manifestations of HIV disease. AB - The neuropsychiatric manifestations of HIV disease include neurobiologic and psychobiologic phenomena. The former consist of primary CNS complications caused directly by HIV, and include cognitive disorders (mild neurocognitive disorder and HIV-associated dementia) and other CNS diseases such as myelopathy and the demyelinating neuropathies; and secondary disorders (principally deliria) occasioned by opportunistic infections, neoplasms, cerebrovascular events, and the effects of metabolic derangements and medications. The latter (psychobiologic) phenomena reflect efforts to cope with various nodal, or transition points, in HIV disease; such points of transition include time of serostatus determination, adaptation to asymptomatic seropositivity, response to early medical symptomatology, and later transition to frank AIDS. Anxiety symptoms and various efforts to cope with anxiety (e.g., denial, anger, withdrawal, hypochondriacal preoccupation) all can punctuate these transition points. Additionally, there may be reactivation of long-standing psychopathology (e.g., depression) in seropositive individuals who tend to belong to a group that has an elevated prevalence of pre-infection psychiatric disorder. These interacting neurobiologic and psychobiologic phenomena pose challenges to the psychiatrist who must develop a good understanding of the medical aspects of HIV infection, as well as the neuropsychiatry of AIDS. In this way psychiatric physicians can play an important role in early identification of neuropsychiatric complications, assist the medical team to anticipate emotional and behavioral disturbances, and develop treatment plans that maximize our ability to help those with HIV infection achieve the best possible quality of life. PMID- 8190665 TI - Management of neurobehavioral impairment in HIV-1 infection. AB - HIV dementing illness recently has been delineated into two categories, HIV associated minor cognitive/motor disorder that may or may not progress to an actual dementia, and HIV-associated dementia complex. At this time, these disorders are distinguished by severity of impairment. As such, each disorder presents with different management problems and thus requires different types of interventions. A model of patient management has been presented herein for each disorder, enumerating possible management problems and practical strategies to address them. Health care providers, in their role as consultants, can educate patients and caregivers about patient management, thus improving quality of life for all involved. The presented paradigm for patient management is based on current knowledge of HIV dementing illness and thus is clearly lacking. Critical issues still exist, in regards to the characterization of the behavioral and cognitive changes associated with HIV infection. The course of this neuropsychiatric illness remains poorly defined, and the progressivity of this illness, while at times is quite certain, is not always so certain. What differentiates those who progress to an end-stage dementia versus those who stop short is unclear. Additional neuropsychiatric research obviously needs to be done, but for individuals with HIV-related neurologic disorders, practical issues are pressing. Specialized residential programs need to be implemented and additional medical and financial services need to be more readily available. Health care providers can serve a crucial role here in making these needs known and actively promoting change in the current health care system. PMID- 8190666 TI - The University of California at San Francisco AIDS Health Project. A community psychiatry approach to the AIDS epidemic. AB - Each program within the AIDS Health Project is designed to work with individuals at different points along the continuum between a state of health at one end of the spectrum and the clinical disorder of AIDS at the other. Thus, individual programs reflect different levels of prevention. For example, the Prevention and Support Services (formerly the Worried Well) Program is an example of primary prevention; i.e., services are provided to healthy individuals who are at risk in an attempt to keep them from contracting the disease. The HIV Positives Being Positive Program is an example of secondary prevention in which services are provided to those who have premonitory symptoms of disease but have not yet developed the full-blown illness. The AIDS antibody counseling and testing program has elements of both primary and secondary prevention, as individuals who are counseled may prove to have either a positive or a negative test. Finally, the Mental Health Program at San Francisco General Hospital and the AIDS and Substance Abuse Program (ASAP) are examples of tertiary prevention. (Note: The ASAP actually incorporates all three levels of prevention through its various activities. As the original impetus for its development was to provide services to people with AIDS, however, we have listed it as a tertiary program.) In these programs, services are provided to individuals with the illness in an attempt to prevent psychological decompensation, to provide relief of current distress, and, perhaps, to delay disease progression. PMID- 8190667 TI - Effect of HIV treatment on cognition, behavior, and emotion. AB - Although not the most common cause, drug therapy does cause changes in cognition, emotion, or behavior in HIV-infected patients. Clinicians need to be aware of the range of known side effects of drugs for HIV infection. Clinicians also must be vigilant to the possibility of a side effect not previously reported because experience with these drugs, especially in combination with one another, is limited. PMID- 8190668 TI - Stress and coping in caregiving partners of men with AIDS. AB - HIV disease presents profound challenges to primary caregivers including adjusting to the care recipient's disease progression, having increasing responsibilities for decision making as the disease progresses, responding to unexpected improvement, having to deal with a virtually uncontrollable disease, and managing role conflict and fatigue. Caregivers who are themselves infected with HIV face additional challenges. Caregiving partners of men with AIDS have high levels of dysphoric mood but, at the same time, they report levels of positive morale that are comparable to community norms. Caregivers sustain positive morale by deriving meaning from their caregiving. Health professionals are in a good position to support caregivers and, thereby, help their patients. PMID- 8190669 TI - Psychoneuroimmunology of HIV infection. AB - The biological pathways exist that could allow psychological factors to alter immune status in HIV-positive individuals. It yet remains to be determined whether such factors can, in fact, act as cofactors in HIV progression. The biology of AIDS is complex, and a multitude of processes may act on HIV progression and complicate studies in this area. The search for modifiable host factors that may alter the progression of HIV infection, however, is an important part of AIDS research and deserves the careful attention of behavioral and biological scientists. PMID- 8190670 TI - Substance abuse and HIV infection. AB - This article reviews what is known about the relationships between recreational psychoactive substance use and HIV infection and sexual behaviors that can transmit HIV. The focus of this article is on nonparenterally used recreational substances and their relationship to HIV transmission behaviors, specifically high-risk sexual behaviors of one of the largest groups of persons at risk for infection--self-identified gay and bisexual men. Published and unpublished studies in this area are reviewed in terms of a hierarchy of epidemiologic evidence that ranges from global associations between substance use and high-risk sexual behaviors to prospective studies of substance use in the context of sexual encounters and incident rates of HIV infection. This article also discusses the secondary community impact of these associations and their intervention implications. PMID- 8190671 TI - Laboratory evaluations in HIV-1-associated cognitive/motor complex. AB - Laboratory tests can provide useful information about the presence and effects of HIV-1 in the CNS, but have thus far not yielded definitive diagnostic or prognostic markers of HIV-1-related cognitive and motor complex. The most clinically useful laboratory procedures are MR imaging and CSF examinations. The routine clinical use of MR imaging and CSF examinations, however, is still restricted to providing information for detecting and excluding secondary effects of HIV-1 infection. MR imaging and CT do not appear to be sensitive enough at current resolutions to provide early detection of HIV-1 CNS effects nor to follow disease progression. Several CSF variables are extremely promising as early markers of primary HIV-1 infection of the brain, and may provide preclinical indications for onset of treatment and for evaluation of treatment efficacy. These include CSF quinolinic acid levels, acid dissociated p24 antigen levels, neopterin or beta 2m, intrathecal IgG synthesis rate, and possibly quantitated PCR levels of HIV-1 viral load. Procedures such as nuclear magnetic resonance spectroscopy, SPECT, PET, computerized EEG, EP, and ERPs are all promising candidates for early detection or localization of HIV-1-related brain dysfunction, but at this time all must still be considered primarily research tools. Before any of these procedures can provide reliable diagnostic and prognostic information about primary HIV-1 neurologic disease, currently on-going longitudinal evaluations of large numbers of asymptomatic HIV-1-infected individuals as they progress to neurologically symptomatic disease must be completed. There is currently no laboratory marker in blood or CSF that definitively predicts the risk for HIV-1-associated cognitive/motor complex. HIV 1-associated cognitive/motor complex remains a clinical diagnosis, which is made on the basis of positive neurologic signs and symptoms and abnormal neuropsychological findings after other causes of neurologic disease are excluded. Laboratory measures, such as the electrophysiologic methods and some CSF variables, are likely to remain adjuncts to the diagnosis because, with few exceptions, they provide data that are nonspecific as to etiopathogenesis. Dynamic imaging, electrophysiologic methods, and CSF indices provide presumptive evidence for the presence of HIV-1-associated CNS damage, and with clinical and neuropsychological evidence, could be used to establish a new definition of primary HIV-1-associated CNS disease along the lines used in establishing a diagnosis of multiple sclerosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8190672 TI - Clinton plan. PMID- 8190673 TI - Erythema occipitalis traumaticum and stork bite. PMID- 8190674 TI - The 1994 health care reform debate: voicing orthopedic concerns about access to specialty care. PMID- 8190675 TI - The orthopedic work force and the effects of health care reform. PMID- 8190676 TI - Lumbar herniated disk disease: comparison of MRI, myelography, and post myelographic CT scan with surgical findings. AB - One hundred eighty patients with suspected lumbar disk disease were evaluated preoperatively with magnetic resonance imaging (MRI), myelography, and post myelogram computerized tomography (CT) scan. Sixty patients underwent surgery on 102 disk levels, allowing for anatomic confirmation of the diagnosis. Eight negative explorations were performed. The correlation between preoperative interpretations of each test and the observed surgical findings was analyzed statistically. Based on this analysis, MRI accurately predicted the operative findings in 98 of 102 disk levels (96%), while the accuracy of myelography (81%) and post-myelogram CT scan (57%) was significantly less. When myelography and CT scan were utilized jointly, the accuracy was 84%, a significant improvement over either test alone, as a diagnostic modality. There was only one false positive MRI study in the evaluation of lumbar herniated disk. The results of this study reflect that MRI is a clinically superior diagnostic test in the evaluation of patients with suspected lumbar disk herniation, and that it should be the diagnostic study of choice when available. Its noninvasive nature, multiplanar capabilities, and the lack of ionizing radiation are particularly desirable for patient and physician. PMID- 8190677 TI - The effect of postoperative wound drainage reinfusion in reducing the need for blood transfusions in elective total joint arthroplasty: a prospective, randomized study. AB - A prospective, randomized study was conducted in 24 patients using the Solcotrans Orthopaedic Drainage Reinfusion System (Smith & Nephew Richards Inc, Memphis, Tenn) for postoperative blood salvage in total joint arthroplasty. The amount of postoperative autologous blood salvage averaged 946 mL. Only 25% of the study group required postoperative transfusions, compared to 83% of the control group (P = .016). In total knee arthroplasties, only 11% of the study group required transfusions, compared to 78% of the control group (P = .018). There were no transfusion reactions, infectious complications, or coagulopathies. Postoperative blood salvage is a safe, reliable, and effective source of autologous blood. PMID- 8190678 TI - Total hip replacement in patients with osteoarthritis of the hip: improvement in pain and functional status. AB - A simple, self-rating questionnaire was developed to assess the clinical outcome related to pain and function after total hip replacement surgery followed by physical therapy. Twenty-two patients, 57 to 86 years of age, with osteoarthritis of the hip who underwent total hip replacement surgery and received physical therapy following surgery, participated in the study. A questionnaire consisting of 11 items was developed to ascertain the level of pain, functional ability and the assistive ambulatory device used to perform selected activities of daily living. A maximum cumulative score of 55 points was possible. The functional categories monitored included: sitting, standing, sleeping, functional walking, distance walking, stair climbing, sitting/standing from a toilet seat, driving, and sexual activities. The questionnaires were completed preoperatively, and postoperatively at 3 and 6 months. The results showed an overall improvement of 56% at 3 months and 64% at 6 months after surgery. Twenty of 22 patients obtained "excellent" results with total hip replacement surgery and follow-up physical therapy. Results of this study indicated that total hip replacement followed by physical therapy decreases joint pain and improves function in patients with osteoarthritis of the hip. PMID- 8190679 TI - The use of ketorolac in the management of postoperative pain. AB - Ketorolac tromethamine (Toradol) is a nonsteroidal antiinflammatory drug (NSAID) available in intramuscular (IM) and oral formulations for the management of acute pain. Intramuscular ketorolac is the only parenteral NSAID available for analgesic use in the US. The clinical profile is reviewed, and clinical studies most applicable to a postoperative patient are discussed in detail. The results of a clinical study performed at Emory University School of Medicine are presented. In this single-dose study, 176 patients received either 10 mg of oral ketorolac, 5 mg or 10 mg of IM morphine, or placebo after orthopedic surgery. The analgesic efficacy of ketorolac was comparable to both doses of morphine and significantly superior to placebo. Ketorolac, when administered intramuscularly or orally, is a safe and effective analgesic agent for the short-term management of acute postoperative pain and can be used as an alternative to opioid therapy. PMID- 8190681 TI - Failed metal-backed patella in total knee arthroplasty. PMID- 8190680 TI - Tensile bonding strength of the cement-prosthesis interface. AB - A widely held belief among orthopedic surgeons is that there is no adhesion between polymethylmethacrylate bone cement and metal. However, a bond does form between the cement and the standard grit-blasted implant finish. Moreover, it has been shown that disruption of this bond or "debonding" of this interface is a major factor in the initiation of failure of some cemented total joint arthroplasties. It is the purpose of this study to determine the tensile pull-off strength of the bone cement-implant surface interface. A 1.27 cm (0.5 in) layer of Simplex-P bone cement was cured between two Co-Cr-Mo pins of 2.22 cm (0.875 in) diameter which had the standard implant finish on the surface that was interfaced with the cement. The specimens were tested in an MTS machine in stroke control with a cross head rate of 1 in per minute. The maximum load to failure was recorded. Bonding of the cement to the surface does occur. The tensile pull off strength of the bone cement-implant surface interface is approximately 5 MPa. Other studies have shown that maintaining this bond between the stem and cement is important in maintaining the stability of cemented total joint arthroplasties. PMID- 8190682 TI - Giant cell tumors in carpal bones. PMID- 8190683 TI - Femoral fractures associated with loose cemented total hip arthroplasty. PMID- 8190684 TI - Malignant fibrous histiocytoma of the patella. PMID- 8190685 TI - Parallel miniature screw fixation of spiral and long oblique hand phalangeal fractures. PMID- 8190686 TI - Evaluation of knee extension following anterior cruciate ligament reconstruction. PMID- 8190687 TI - Radiologic case study. Multiple synchronous extensor tendon rupture. PMID- 8190688 TI - Community as client: a challenge for nursing education. AB - The mandate of public health departments has been, and continues to be, to provide and deliver a variety of health programs and services pertinent to local circumstances and needs. Public health nurses are the largest group of health care professionals who deliver these services. The objectives of this paper are to identify what policy makers expect of public health nurses related to community development for health, and to describe the educational components necessary for baccalaureate nursing curricula if these expectations are to be met. PMID- 8190689 TI - Immunization status of 2-year-olds in middle/upper- and lower-income populations: a community survey. AB - Immunization rates of preschool children in the United States are well below recommended levels. Whereas low-income and minority groups have been targeted as at risk for inadequate immunization, the assumption is generally made that middle/upper-income children are adequately immunized through the private sector. We conducted a community-based survey that refutes this assumption. Only 31% of the 302 parents surveyed reported full immunization of their 2-year-olds. No significant differences were found in the immunization rates for middle/upper income (34% immunized) versus lower-income children (28% immunized). Failure to receive the 18-month doses of DTP and polio was the most frequent cause of inadequate coverage for both groups. Barriers to immunization reported by middle/upper- and lower-income parents were similar, with over one-third of the parents identifying cost and lack of insurance coverage as problems. Additional barriers related to methods of operations of providers. Findings have immediate implications for public health nurses in terms of assessing coverage of their own preschool populations and introducing corrective actions to improve levels of immunization. PMID- 8190690 TI - Community health clinical experiences: the primary care setting. AB - Applying the nursing process to the health of populations is a challenge in undergraduate community health nursing education. We evaluated a method of applying the process in primary health care settings. Key factors were using case management and other means to assess systems from the client's perspective, assessing population needs, diagnosing community needs-service mismatch, planning in partnership with communities, and implementing and evaluating plans. Because these are difficult, if not impossible, to accomplish in a one-semester undergraduate course, students transferred projects and cases from one semester to another. Case management is the principal interface of students to individual and family clients. PMID- 8190691 TI - Daily stressors and coping responses: a comparison of rural and suburban children. AB - Although research has examined problems of stress and health among rural families, little is known about coping phenomena directly from the perspective of rural children. This study compared two groups of children, one rural and the other suburban, in their reports of daily stressors and coping efforts as actually experienced. Using semistructured diaries over a period of six weeks, 21 rural children and 23 suburban children reported daily sources of stress, coping efforts, and coping resources. Rural children were more compliant in completing diaries. They reported more internal, cognitive-intrapsychic source of stress, whereas suburban children listed more external environmental sources. Suburban boys reported submission as the most common coping response, and rural boys listed organized activities and problem-solving approaches. Other interesting differences between the rural and suburban children, and gender differences among both groups emerged. PMID- 8190692 TI - Health promotion in child and family health care: the role of Finnish public health nurses. AB - Starting from a theoretical model for the work of public health nurses, we explored the knowledge, skills, and decision making of Finnish public health nurses in the context of their efforts to maintain and promote child and family welfare. The results indicate that the nurses' knowledge basis and skills cover the concepts included in the theoretical model. The nurses tackle existing situations in the lives of children and their family, attempt to solve the current problems, and together with parents, make collaborative decisions. No attempts are made to produce long-term health care plans. The model seemed to work fairly well in promoting children's welfare, but less so in the case of families. Finnish public health nurses follow the official guidelines governing the work of child welfare clinics, but they set fewer individual goals for children and families. PMID- 8190693 TI - Evaluation of group health promotion with community-dwelling older women. AB - Health promotion outcomes with older adults are characterized increasingly in terms of several effects. The outcomes of a health-promotion intervention with a group consisting of a majority of African-American older women were evaluated after six months. The study employed a quasi-experimental design with intervention and control groups all living in the area of a midwestern city with the highest proportion of low-income and non-Caucasian elders. Women in the intervention group participated in weekly group meetings over 26 weeks. The intervention was derived from the ecologic well being model and incorporated content related to three areas of outcome evaluation: health practices, psychologic and spiritual well-being, and social integration. Interviews conducted prior to and on conclusion of the intervention incorporated four single item qualitative measures and the following three instruments as outcome measures: the senior lifestyle inventory, the integration inventory, and the social integration subscale. Although no significant increases in outcomes were demonstrated over time for the intervention group, statistical analysis before and after the intervention did reveal significant contrasts among controls in relation to well-being, health practices, and life satisfaction, suggesting a preventive-maintenance effect for the participants. PMID- 8190694 TI - Breast self-examination beliefs: a descriptive study. AB - Breast cancer is a major cause of morbidity and mortality among American women. Evidence indicates that regular breast self-examination (BSE) may reduce breast cancer mortality by 18%, yet the majority of women do not practice it. This study used a decision model to examine the BSE-related characteristics, beliefs, and behaviors of 52 working women age 21 to 65 years (mean 44.05 yrs). Nearly 29% of the sample performed BSE. They were more likely than nonperformers to be white, to have a close relative who had breast cancer, and to believe that breast problems could be detected through BSE. Fears, particularly fear of cancer, were more likely to affect performers' than nonperformers' BSE decision. Nonperformers were more likely to think that the first symptom of breast cancer would be a sensation of some type, and that a healthy lifestyle protected them from the disease. They also were more likely to think reminders would encourage them to perform BSE. The most often reported sources of information about BSE were health care providers and friends or relatives. PMID- 8190695 TI - Mississippi public health nurses and midwives: a partnership that worked. AB - At the turn of the century maternal and infant mortality rates were high in this southern state. Untrained midwives conducted many of the deliveries. Initial support for locating and training midwives by public health nurses was provided by the American Red Cross and the United States Public Health Services. Later, funding from a philanthropic organization (Rockefeller International Foundation) provided a mechanism that brought Mississippi public health nurses and midwives to a partnership that endured for over a half a century, and contributed to better maternal-infant health care outcomes for that state. PMID- 8190696 TI - A primary health care approach using Hispanic outreach workers as nurse extenders. AB - In an effort to improve the health of Hispanic families, particularly prenatal women and infants, the county health department instituted a program of intensified home visits using bilingual, bicultural nurse extenders within a framework of primary health care. The outreach workers offer basic health information to improve families' skills and knowledge, and to assist with linkages to community resources. Public health nurses provide assessment, establish a plan of care, evaluate progress, and supervise the workers. The program has resulted in increased numbers of individuals receiving services, more women registering earlier for prenatal care and the Women, Infants, and Children's (WIC) program, and increased numbers of infants receiving WIC services and regular medical supervision. Public health nurses report increased knowledge and positive changes in families' health behaviors. In addition, the program has strengthened relationships between the health department and Hispanic families. PMID- 8190697 TI - One-year treatment of streptozotocin-induced diabetic rats with vanadyl sulphate. AB - Streptozotocin-diabetic and non-diabetic rats were given various concentrations of vanadyl sulphate in drinking water for one year. It was found that vanadyl sulphate caused significant decreases in body weight gain and plasma insulin level in non-diabetic rats, but did not significantly alter fluid and food intakes or plasma levels of glucose, triglycerides, or cholesterol. In diabetic animals, vanadyl treatment significantly alleviated or prevented the occurrence of hyperglycaemia, hypoinsulinaemia, hyperphagia, polydipsia, hyperlipidaemia, or cataract formation, but the slower body weight gain was not improved. There were gradual decreases in the intake of the compound required to correct hyperglycaemia in the values of ED50 with age of the rats. The beneficial effects of vanadyl treatment persisted 16 weeks following the withdrawal of the compound. It is concluded that vanadyl sulphate is an effective agent for chronic therapy of streptozotocin-induced diabetes in rats, and its prolonged use does not lead to the development of tolerance. PMID- 8190698 TI - One-year treatment of non-diabetic and streptozotocin-diabetic rats with vanadyl sulphate did not alter blood pressure or haematological indices. AB - Circulatory and haematological effects of chronic administration of vanadyl sulphate in drinking water for one year in non-diabetic and streptozotocin diabetic rats were investigated. At various time points during the treatment period and at 13 weeks following its withdrawal, systolic blood pressure and pulse rate were measured using a tail-cuff method and some selected haematological indices, including haematocrit, haemoglobin, erythrocyte count, reticulocyte percentage, leukocyte count, platelet count, and leukocyte composition of the peripheral blood were determined using standard methods. It was found that prolonged treatment of either nondiabetic or streptozotocin diabetic rats with vanadyl sulphate did not cause significant changes in the parameters observed but significantly alleviated the occurrence of bradycardia and the decreased leukocyte count in the peripheral blood in streptozotocin diabetic animals. No significant changes in systolic blood pressure, pulse rate, or haematological indices were observed following the withdrawal of vanadyl sulphate, except that the previously vanadyl-treated diabetic rats were found to have higher leukocyte count, platelet count and neutrophil percentage, and lower lymphocyte percentage in their leukocyte composition. It is concluded that vanadyl sulphate does not have a hypertensive effect nor is it significantly toxic to the haemopoietic system in rats. PMID- 8190699 TI - Function of the auditory and visual systems, and of peripheral nerve, in rats after long-term combined exposure to n-hexane and methylated benzene derivatives. I. Toluene. AB - Rats were exposed to n-hexane, toluene, or toluene together with n-hexane, each solvent 1000 p.p.m. (1000 + 1000 p.p.m. in combined exposure), 21 hr/day, 7 days/week during 28 days. Neurophysiological recordings were made 2 days, 3 months, and one year after end of exposure. A reduction in auditory sensitivity, recorded by click evoked auditory brainstem response, was observed 2 days after exposure to toluene alone, or to toluene together with n-hexane, but not after exposure to n-hexane alone. The reduction lasted one year after the exposure. Three months after combined exposure, a synergistic enhancement of loss of auditory sensitivity was observed in the mixed exposure group. One amplitude in the flash evoked potentials was lowered in the n-hexane exposed group 2 days after exposure. No such reduction was seen after simultaneous exposure to toluene. Exposure to n-hexane alone caused a marked decrease in peripheral nerve conduction velocity 2 days and 3 months after exposure, while exposure to n hexane together with toluene had only a small effect on this velocity. PMID- 8190701 TI - Characterization of the CGRP receptor and mechanisms of action in rat mesenteric small arteries. AB - Rat alpha-calcitonin gene-related peptide-induced concentration-dependent (100 pM 10 nM) relaxations in rat mesenteric small arteries (i.d. approximately 220 microns) contracted with noradrenaline, prostaglandin F2 alpha or K+, however, the maximal relaxation depended on the precontractile stimulus, being highest (95%) in arteries contracted with PGF2 alpha and lowest (51%) in arteries contracted with 125 mM K+. The relaxation was inhibited between 10 pM and 1 nM by removal of the endothelium, but was not antagonized by glibenclamide (1 microM), tetraethylammonium (30 mM), apamine (0.3 microM) and 4-aminopyridine (3 mM). The concentration-response curve to rat alpha-CGRP and human beta-CGRP was shifted to the right in the presence of 1 microM human alpha-CGRP(8-37) indicating a receptor affinity, -log(KB[M]), equal to 7.2 and 7.0, respectively. It is concluded that the relaxation induced by CGRP depends minimally on the endothelium and K(+)-channel opening is not a principal process in the relaxing effect of CGRP, thus a third mechanism must mediate the relaxation in these vessels. The main CGRP receptor type mediating relaxation in rat mesenteric small arteries belongs to the CGRP1 subtype. PMID- 8190700 TI - Function of the auditory and visual systems, and of peripheral nerve, in rats after long-term combined exposure to n-hexane and methylated benzene derivatives. II. Xylene. AB - Rats were exposed to xylene, to n-hexane, or to xylene together with n-hexane, each solvent 1000 p.p.m. (1000 + 1000 p.p.m. in mixed exposure), 18 hr/day, 7 days/week during 61 days. Neurophysiological recordings were made 2 days, 4 months, and 10 months after the end of exposure. Exposure to n-hexane alone, or xylene alone, caused a slight loss of auditory sensitivity as recorded by auditory brainstem response 2 days after the exposure. Exposure to n-hexane together with xylene caused persistent loss of auditory sensitivity (7-17 dB; P < 0.05) which was non-additively enhanced (P < 0.01). The latencies of the flash evoked potentials in the group exposed to n-hexane alone were prolonged (re C group) 2 days after exposure, while smaller prolongations were found in the group exposed to xylene together with n-hexane. Exposure to n-hexane alone caused a marked decrease in nerve conduction velocity, while simultaneous exposure to xylene inhibited n-hexane-induced velocity reduction in peripheral nerve (P < 0.01). PMID- 8190702 TI - Alternative pathways of sulfite oxidation in human polymorphonuclear leukocytes. AB - Sodium sulfite is metabolized by human polymorphonuclear leukocytes by two alternative pathways, one enzymatic route dependent on sulfite oxidase and one non-enzymatic which involves intermediate formation of sulfur trioxide anion radicals. Initiation of the oxidative burst by phorbol myristate acetate significantly stimulates sulfate formation through the second pathway. The activity of sulfite oxidase in polymorphonuclear leukocytes varies greatly among individuals, a variation consistent with the suggested polymorphic distribution of sulfite oxidase in the human population. PMID- 8190703 TI - Effects of terbutaline on alpha-adrenergic responses and Ca2+ influx in isolated rabbit aorta. AB - Effects of terbutaline applied in vivo or in vitro on alpha-adrenergic receptors in the rabbit aorta in normal and Ca(2+)-free solution, and on basal, high potassium-, and phenylephrine-stimulated Ca2+ uptake into aorta were investigated. Three day terbutaline administration (25 mg/kg, subcutaneously three times daily) to rabbits increased the pKB for phentolamine in aorta rings (control 7.3 +/- 0.2, n = 9; terbutaline 7.8 +/- 0.2, n = 15). It also depressed phenylephrine-stimulated contractions of aorta rings in Ca(2+)-free but not those in normal Krebs solution. It did not significantly depress the basal, or phenylephrine-evoked Ca2+ influx into aorta rings, but decreased high potassium induced Ca(2+)-influx (control 0.58 +/- 0.05 mumoles/g aorta; n = 3, terbutaline 0.41 +/- 0.06 mumoles/g aorta, n = 3). In vitro application of 50 microM terbutaline did not significantly alter phenylephrine-stimulated contractions of aorta rings in Ca(2+)-free Krebs solution or significantly depress basal or phenylephrine-induced Ca2+ influx into aortas, but did decrease high potassium stimulated Ca(2+)-influx. Thus, 3-day terbutaline administration increased the affinity of alpha-adrenergic receptors for phentolamine and had a tendency to increase contractions of aorta rings to phenylephrine. It also decreased high potassium-stimulated Ca2+ influx, and depressed phenylephrine-induced contractions in Ca(2+)-free Krebs solution, while in vitro terbutaline application also decreased potassium-induced Ca2+ influx. PMID- 8190704 TI - Lipoperoxidative damage on lead exposure in rat brain and its implications on membrane bound enzymes. AB - We have investigated the effect of lead exposure on lipid peroxidation, a deteriorative process of the membranes, in the different regions of the brain. Lead treatment (50 mg/kg b.wt. intragastrically) for a period of eight weeks to rats resulted in a significant accumulation of lead in all the regions of brain, at maximum in hippocampus. The lipid peroxidation was accentuated following lead exposure and there was a linear correlation between the increase in lipid peroxidation and increase in lead levels (r = 0.75). The antioxidant capacity of the neuronal cells in terms of the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase was diminished. Lead treatment also altered the glutathione status i.e. levels of reduced glutathione were lowered, accompanied with the accumulation of oxidized glutathione. Furthermore, the activity of glutathione reductase was significantly lowered in lead-treated animals. The activity of membrane bound enzyme acetylcholinesterase was significantly inhibited following lead exposure and there was a linear correlation between the increase in lipid peroxidation and decrease in acetylcholinesterase activity (r = -0.83). It appears from the results that lead may exert its neurotoxic effects via peroxidative damage to the membranes. PMID- 8190705 TI - Immunoglobulin levels in workers exposed to inorganic mercury. AB - The serum immunoglobulin (IgG, IgM and IgA) concentrations of 44 mercury-exposed workers were examined and compared with those of non-exposed, age- and sex matched individuals. At the time of testing, the exposed population had a mean (+/- S.D.) mercury urinary concentration of 24.7 +/- 19.1 and in 40 of them urinary mercury levels were below the currently accepted limit of 50 micrograms/g creatinine. Increased IgG, IgA and IgM levels were found in the mercury-exposed individuals and in 16, a second evaluation was performed six months later. During the intervening six months, the level of hygiene was improved throughout the plant, and urinary mercury concentrations were determined monthly in each worker. Despite a significant reduction in mercury urinary concentrations, serum immunoglobulin levels did not return to the normal range. There was no correlation between the length or level of exposure and the immunoglobulin levels. Liver protein synthesis, as studied by factor V, prothrombin time, prealbumin and transaminase activity, was normal and liver injury, as evaluated by serum aspartate and alanine aminotransferase activities (AST and ALT, respectively), was not observed. No haematological abnormalities were noted. These results indicate that "safe" levels of mercury exposure may lead to humoral immunological stimulation. PMID- 8190706 TI - Cadmium mobilization by monoaralkyl- and monoalkyl esters of meso-2,3 dimercaptosuccinic acid and by a dithiocarbamate. AB - Syntheses and relative cadmium mobilizing properties are described for three new monoaralkyl esters (HOOCCH(SH)CH(SH)COOR, where R = phenylethyl ((CH2)2C6H5), MPhEDMS; R = 3-phenylpropyl ((CH2)3C6H5), MPhPDMS; and R = 2-phenoxyethyl ((CH2)2OC6H5). MPhOEDMS) of meso-2,3-dimercaptusuccinic acid. These were prepared by the reaction of the corresponding alcohol with meso-2,3-dimercaptosuccinic acid (DMSA) in aqueous HCl. When administered intraperitoneally to cadmium-loaded mice at 0.50 mmol/kg/day for four consecutive days, all induced significant reductions in the whole body cadmium levels. MPhEDMS, 60%; MPhPDMS, 66%; and MPhOEDMS, 58% in comparison with control levels. At the same dosage monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) and a dithiocarbamate, sodium N-benzyl-4-O (beta-D-galactopyranosyl)-D-glucamine-N-carbodithioate++ + (BLDTC) induced reductions of 65% and 57%, respectively. Hepatic and renal cadmium were also depleted significantly, while brain cadmium levels were unchanged. These compounds induced a significant reduction in the cadmium levels of the spleen, and one, MPhOEDMS, produced a 10% decrease in pancreatic cadmium. The manner in which the later injections removed smaller fractions of the total body cadmium is consistent with a bodily distribution of these compounds by which they are concentrated primarily in the kidneys and the liver, with much smaller amounts reaching other organs. It is proposed that these compounds enter renal and hepatic cells through an anion transport system. PMID- 8190707 TI - The effect of three products of cigarette smoke (cyanide, thiocyanate and nicotine) on the concentration-response curves of 5-hydroxytryptamine, norepinephrine and epinephrine in the isolated human umbilical veins and arteries. AB - The effect of cyanide (10(-7) M), thiocyanate (10(-4) M) and nicotine (10(-7) M) on the concentration-response curves of 5-hydroxytryptamine, norepinephrine and epinephrine were investigated in human isolated umbilical arteries and veins. Cyanide significantly affected the responses of arterial strips to 5 hydroxytryptamine, norepinephrine and epinephrine: It caused significant leftward shifts of the 5-hydroxytryptamine concentration-response curves and significantly potentiated the contractile effects of norepinephrine and epinephrine in the case of norepinephrine, and epinephrine concentration reached 10(-6) and 10(-7) M respectively in the bath medium. Cyanide did not show any significant effect on the concentration-response curves of 5-hydroxytryptamine, norepinephrine and epinephrine in veins. Nicotine interacted with the response of adrenergic agonists both in arteries and veins; in arteries it potentiates the contractile response of epinephrine; in veins, it inhibited the dilatory responses of norepinephrine and potentiated the contractile effect of high concentration of epinephrine (10(-6) M). Thiocyanate did not cause any difference on any cumulative concentration-response curves either on the vessels. However, none of these individual effects of cyanide and nicotine were observed when the cyanide, thiocyanate and nicotine were added in combination in the isolated organ bath medium. PMID- 8190708 TI - Effect of ascorbate on adriamycin-Fe(3+)-induced lipid peroxidation and DNA damage. AB - Adriamycin-Fe(3+)-induced lipid peroxidation was enhanced by ascorbate at low concentrations. High concentrations of ascorbate also enhanced the peroxidation reaction, but only at an early stage. The initial rate of peroxidation depended upon the ratio of adriamycin-Fe2+/adriamycin-Fe3+ and the maximum rate was observed at the ratio of 1:1. These results suggest that the adriamycin-Fe(3+) induced lipid peroxidation may be initiated by an adriamycin-Fe(2+)-oxygen adriamycin-Fe3+ complex. Ascorbate also promoted bathophenanthroline-Fe2+ formation from adriamycin-Fe3+ in a dose-dependent manner. It seems likely that ascorbate influences the peroxidation reaction via the reduction of adriamycin Fe3+. During the interaction of adriamycin-Fe3+ with ascorbate, deoxyribose was not degraded, suggesting that hydroxyl radical formation did not occur. In contrast, plasmid PM2 DNA was readily damaged during the interaction of adriamycin-Fe3+ with ascorbate. Catalase, mannitol and dimethylsulfoxide prevented DNA damage. No DNA damage occurred when the reaction was run under nitrogen gas, indicating that oxygen is involved. PMID- 8190709 TI - Chronic L-alpha-glyceryl-phosphoryl-choline increases inositol phosphate formation in brain slices and neuronal cultures. AB - Repeated, but not single injections of L-alpha-glyceryl-phosphorylcholine (alpha GPC) significantly increased basal [3H]inositol monophosphate (InsP) formation in hippocampal, cortical, and striatal slices of male rats. The effect was dose dependent and was accompanied by an increased incorporation of [3H]inositol into the phospholipid fraction. Incubation of brain slices with different neurotransmitter antagonists, such as atropine, prazosin, or L-2-amino-4 phosphonobutanoate (L-AP4) did not modify the increase in [3H]InsP formation produced by alpha GPC, suggesting that the effect is not mediated by an increased availability of a specific neurotransmitter. Similar results were obtained in cerebellar and cortico-striatal neurones in primary culture exposed to daily addition of alpha GPC since the second day of maturation in vitro. We suggest that alpha GPC treatment may result in an increased rate of phospholipid synthesis, including the phosphoinositides available for signal transduction at central nervous system level. PMID- 8190710 TI - Goat immunoglobulin purification on phosphocellulose and DEAE Affi-Gel blue. AB - We describe a method for the efficient purification of immunoglobulins G (IgG) to near homogeneity from goat serum. This was achieved by performing first an AS-40 fractionation on goat serum, followed by chromatography on phosphocellulose (P11) equilibrated in citrate buffer at pH 5.7. Peak I, eluted at V0 from P11, contained all IgG and the other serum proteins, except beta-globulins and most of the alpha-2-globulins, which are eluted in a second peak with 0.24 M K-phosphate in citrate buffer at pH 6.0. Peak I, concentrated and dialyzed in 20 mM K phosphate buffer pH 8.0, was then applied onto a DEAE Affi-Gel Blue column equilibrated in the same buffer. Two peaks were obtained from this column: peak I, eluted at V0 contained a pure IgG fraction, while the other serum proteins were in peak II. We conclude that the P11 step, performed under the conditions we report here, is very useful to retain the alpha-2 and beta-globulins, which contaminate the IgG when only the DEAE Affi-Gel Blue purification step is used. PMID- 8190711 TI - A simple and efficient method for the purification of seminal plasmin, an antimicrobial protein from bovine seminal plasma. AB - A method involving direct affinity chromatography of undialysed bovine seminal plasma on a calmodulin-agarose column was developed for the purification of seminalplasmin. Seminalplasmin thus obtained was further purified from any contaminants left by ion-exchange chromatography on a short CM-Sepharose column. The method gave an excellent yield of seminalplasmin (0.7 mg per ml seminal plasma) that showed 100% inhibition of bacterial growth at a concentration of 10 micrograms/ml. The purified seminalplasmin was found to be homogeneous as tested by HPLC on a reverse-phase column and SDS-PAGE. PMID- 8190712 TI - Fractionation of carcinoembryonic antigen and related antigens in normal adult feces using a gradient medium Percoll. AB - Fresh normal human feces were fractionated using Percoll gradients and phosphatidylinositol-specific phospholipase C. Studies concerning how cells or cell membrane fragments are fractionated with CEA activity indicate that fecal associated CEA activity is not primarily associated with soluble antigens but with whole cells or fragmented cell membranes. PMID- 8190713 TI - Optimization of synthesis of agarose-based lectin affinity sorbents. AB - Different amounts of wheat germ agglutinin were immobilized to agarose gel, previously activated by different amounts of the coupling agent divinyl sulfone. The effectiveness of these affinity sorbents was characterized specific binding of ovomucoid with the gel. These studies revealed the formation of clear optima in binding capacity of the affinity gel, depending on conditions of its synthesis. The ratio between the concentration of the coupling agent and immobilized lectin were found to be crucial for optimization of binding properties of the affinity sorbent. PMID- 8190714 TI - Recovery of lysozyme from scallop waste. AB - A crude lysozyme preparation was recovered in waste from the scallop processing industry. Lysozyme was then purified 229-fold in preparative scale by chromatography on S Sepharose and Blue Sepharose. Further purification on Sephacryl S-200 resulted in a lysozyme preparation with a specific activity of 64,000 units/mg protein. The apparent molecular mass of the partially purified lysozyme was 10 kDa as judged by gel filtration. Optimum pH for lysis of Micrococus luteus under the present conditions was 5.2. The enzyme was very active at low temperatures. At 4 degrees C the scallop viscera lysozyme exhibits about 55% of the activity measured at 37 degrees C. PMID- 8190715 TI - Role of the GP2/THP family of GPI-anchored proteins in membrane trafficking during regulated exocrine secretion. AB - Identification and characterization of the GP2/THP family of GPI-anchored membrane proteins associated with apical secretory membranes suggest that this new class of GPI-linked proteins plays a critical role in regulated protein secretion and ion transport in polarized epithelial cells in pancreas, liver, lung, kidney, and gastrointestinal tract. Based on recent information obtained from the world literature and from our own investigations we present the following two hypotheses capable of unifying previously diverse observations. Hypothesis 1 is that formation of GP2 tetramers in the acidic milieu of the trans Golgi network (TGN) organizes a GP2/proteoglycan (PG) matrix tightly associated with the luminal surface of zymogen granule (ZG) membranes, and proposes that this matrix functions in (a) membrane sorting during granule assembly in the TGN, (b) inactivation of ZG membranes during the storage phase of secretion, and (c) regulated trafficking of ZG membranes from the apical plasma membrane (APM) after exocytosis. Hypothesis 2 is that the acinar lumen constitutes a distinct physiologic compartment for coupled biochemical reactions between acinar and duct cells. Because the acidic pH of the TGN plays a critical role in condensation of secretory proteins, alkalinization of the acinar lumen is required for (a) neutralization of the acidic pH of exocytic contents and (b) solubilization of aggregated (pro)enzymes. Further alkalinization appears to be required for pH dependent release of the GP2/PG matrix from the APM, a process that may regulate internalization of ZG membranes for reuse during secretion. Taken together, the two hypotheses suggest that luminal factors including acid-base interactions and matrix assembly and disassembly processes perform critical functions during regulated storage and release of pancreatic (pro)enzymes. The requirement that coupling reactions be coordinated through the actions of separate hormones [cholecystokinin (CCK) and secretin] on divergent epithelial cells (acinar and duct cells, respectively) provides a new appreciation for the importance of combined CCK and secretin stimulation during pancreatic secretion in response to food intake. PMID- 8190716 TI - Isolation and function of human and pig islets. AB - This report confirms reproducible methods to isolate and assess viability and function of pig and human islets. We processed 10 pig and five human pancreata. The pancreata were digested by a modification of Ricordi's automated method for islet isolation. The number of islet equivalents (150 microns diameter islets) was 335,190 +/- 79,345 islets per pig pancreas (5,146 +/- 1,274 islets/g pig pancreas) and 323,630 +/- 147,810 per human pancreas (6,252 +/- 2,572 islets/g human pancreas). The majority of islets were in the range of 50-200 microns diameter, and 20% of the islet population had a size distribution of 200 microns diameter in both porcine and human models. The purity of the final preparations exceeded 90%. The secretory response of perifused islets showed a biphasic insulin release pattern in both species. Perifused fresh pig islets released 2.5 pmol/L islet-1 min-1 at 2.0 mM glucose and 6.2 pmol/L islet-1 min-1 at 16.7 mM glucose. After 7 days culture at 37 degrees C, human islets released 1.32 pmol/L islet-1 min-1 at 2.0 mM and 12.24 pmol/L islet-1 min-1 at 16.7 mM. These results indicate that this procedure is useful to obtain pure, large, and functional islets from pig and human pancreata. PMID- 8190717 TI - Mutated c-K-ras in small pancreatic adenocarcinomas. AB - The objective of this study was to determine whether small human pancreatic adenocarcinomas contain activated c-K-ras as an approach to answering the question of whether c-K-ras mutation is an early change in this disease. Eight pancreatic adenocarcinomas in the range 1.2-3 cm were analyzed for c-K-ras mutation at codon 12 by amplifying the c-K-ras gene around codon 12 out of paraffin-embedded tissue sections using the polymerase chain reaction. c-K-ras mutations were detected by allele-specific oligonucleotide hybridization. Six of the eight small pancreatic adenocarcinomas contained mutated c-K-ras at codon 12, position 2, and two of the six tumors had an additional mutation at position 1 of codon 12. Our results indicate that small pancreatic adenocarcinomas are similar to large, late-stage pancreatic adenocarcinomas in that 75% of the tumors analyzed contain mutated c-K-ras at codon 12, position 2. These data suggest that c-K-ras mutation occurs early and may therefore have a role in initiation of human pancreatic adenocarcinoma. PMID- 8190718 TI - Phosphoinositide hydrolysis and insulin release in fetal rat islets. AB - The association between phosphoinositide hydrolysis and insulin release in fetal islets was investigated. Islets from 21.5-day-old fetal rats were cultured for 7 days in inositol-free RPMI 1640 containing 11.1 mM glucose and labeled with 20 microCi/ml [3H]inositol for the final 2 days. The labeled islets were then perifused under various conditions for 60 min. Glucose (16.7 mM) caused a modest increase in [3H] efflux from labeled islets, but there was a subsequent fall-off in [3H] efflux. Fetal islets showed the first phase of insulin release without the continued rising second phase. When islets were perifused with 5 mM LiCl, the glucose-induced efflux of [3H] was greatly reduced, whereas glucose-induced insulin release was not affected. A pronounced effect of LiCl was an increase in inositol monophosphate, indicating increased phospholipase C activity. Although marked release of [3H] from labeled islets occurred in the presence of 5 mM inositol, the decreases in radioactive inositol lipid and insulin release induced by glucose were not changed. These data suggest that the fall-off in the second phase of insulin release from fetal islets may be partly due to blunted phosphoinositide hydrolysis. PMID- 8190719 TI - Effect of H-2 compatibility in autoimmune destruction of islet allografts from B10 congenic lines to nonobese diabetic mice. AB - Autoimmune diabetes involves multiple antigens, and both cellular and humoral immune responses. Using CBA (H-2k) C57BL/6 (H-2b), and BALB/c (H-2d) newborn mouse pancreata, we previously demonstrated that acute and strong destruction of islet allografts by anti-islet autoimmunity in the nonobese diabetic (NOD) mouse H-2Kd, Db) is under the influence of major histocompatibility complex (MHC) antigens. In the current study, we have attempted to confirm these results in the absence of minor alloantigenic differences using B10 congenic strains as pancreatic donors. Pancreata from B10.BR (H-2k), C57BL/10SnJ (H-2b), and B10.D2 (H-2d) were transplanted under the kidney capsule of NOD mice within 1 month of diabetes onset. These recipients were immunosuppressed with cyclosporine (CsA) in a dosage that effectively prevents rejection of skin allograft, but not islet isograft destruction that is mediated by anti-islet autoimmunity. On day 10, the grafts were harvested and examined histologically to assess viability. Pancreatic allografts from B10.D2, sharing the H-2Kd with the NOD mouse, showed the strongest lymphocytic infiltration, and neither islets nor beta cells were found in all seven grafts. C57BL/10SnJ grafts, sharing the same H-2Db, also showed severe lymphocytic infiltration, and no intact islets, and only a few beta cells were found, as single cells, in three of eight grafts. In contrast, B10.BR grafts, completely incompatible at the H-2, showed the least infiltration, and normal islets containing many beta cells were found in 10 of 11 grafts. These results again suggested the hypothesis that islet allograft destruction by diabetic NOD mice is MHC restricted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190720 TI - Functional response of a limited beta-cell mass to long-term hyperglycemia. AB - 250 syngeneic islets were implanted either beneath the kidney capsule or into the liver of diabetic LEW 1.A rats to investigate the functional response of a limited mass of beta-cells to long-term hyperglycemia. The number of islets, per se, was expected to be insufficient to reverse the hyperglycemia. All animals were characterized by a substantial body weight gain. Unexpectedly, 29% of the rats with a subrenal and 40% of the animals with a portal islet graft normalized their plasma glucose in 64 +/- 13 and 75 +/- 12 days, respectively. Depending on the glycemic state of the recipients, there was an elevation of the graft insulin content after 120 days over the level at transplantation. The responsiveness of the implanted islets to different secretagogues was tested either in vitro by static incubation of the prepared grafts from the kidney or in situ by perfusion of the islet-containing liver. Grafts of normoglycemic rats showed a pronounced response, although the biphasic profile of the hormone release was lost. In principle, grafts exposed permanently to a hyperglycemic environment have kept their responsiveness, although the insulin outflow was considerably lower. The functional viability of the islets was not influenced by the site of transplantation. Long-term hyperglycemia does not necessarily result in destruction and loss of beta-cells even when their total mass is already limited, but it obviously impairs their functional responsiveness. PMID- 8190722 TI - Modulation of pancreatic secretion by capsaicin-sensitive sensory neurons in the rat. AB - The purpose of this work was to study whether stimulation or destruction of sensory afferents can modulate pancreatic secretion. The neurotoxin capsaicin is specific for a subpopulation of small diameter primary afferent neurons. Small doses of capsaicin were administered to anesthetized rats as intraduodenal or intragastric bolus injections to stimulate digestive sensory fibers, and pancreatic secretory response was measured. In addition, several high-dose subcutaneous capsaicin injections were administered 10 days before the experiments began, in order to inactivate sensory fibers. Basal and 2-deoxy-D glucose (2DG)-stimulated pancreatic secretion was then measured. Intraduodenal capsaicin (96-3,050 micrograms/kg) induced a progressive (peak response 40-60 min after the injection), dose-related and long-lasting (> 180 min) increase in pancreatic output of sodium, bicarbonate, and total protein. The maximal response was obtained with 964 micrograms/kg capsaicin; it amounted to about 15% of the maximal response to exogenous cholecystokinin octapeptide (CCK8). The response was not decreased by atropine, hexamethonium, vagotomy, a mixture of adrenoceptor antagonists (prazosin + idazoxan + propranolol), or by the CCKB receptor antagonist L365,260. In contrast, the CCKA receptor antagonist L364,718 reduced by 30-40% the sodium and bicarbonate response and reduced by 90% the protein response induced by capsaicin, but not the response induced by methacholine or 2DG. However, intraluminal capsaicin did not release CCK in a preparation of isolated perfused duodeno-jejunum. Intragastric capsaicin did not significantly change pancreatic secretion. Capsaicin pretreatment had no effect on basal and 2DG-stimulated secretion, but abolished the response to intraduodenal capsaicin. In conclusion, intraduodenal capsaicin can stimulate external pancreatic secretion in anesthetized rats through capsaicin-sensitive sensory neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190721 TI - Inhibitory effect of calcium channel blockers on growth of pancreatic cancer cells. AB - Calcium, which binds to calmodulin inside the cells, is an important mediator of various intracellular processes, including cell proliferation. We speculated that blockade of Ca2+ influx into the cells by Ca(2+)-channel blockers, such as phenytoin and verapamil, might affect the Ca(2+)-calmodulin pathway leading to suppression of cell growth. In this study, we examined the effect of phenytoin and verapamil on growth of two human pancreatic cancer cell lines, MIA PaCa-2 and CAV, in vitro and in vivo. Both phenytoin and verapamil inhibited growth of the two cell lines in a dose-dependent fashion. Phenytoin and verapamil each significantly prolonged doubling time of MIA PaCa-2 and the combination of the two drugs acted synergistically. The activity of ornithine decarboxylase, which is a rate-limiting enzyme of the polyamine pathway that is closely related to cell proliferation, was significantly inhibited by both drugs in a time-dependent fashion. Phenytoin, but not verapamil, inhibited growth of MIA PaCa-2 tumors xenotransplanted into nude mice, whereas both phenytoin and verapamil inhibited the growth of CAV tumors. Since phenytoin and verapamil are known to have fewer side effects than conventional antineoplastic drugs, these results suggest their possible use in novel therapeutic strategies. PMID- 8190724 TI - A new CCK-A antagonist, KSG-504, administered intraduodenally, inhibits pancreatic secretion in rats. AB - We studied the effect in anesthetized rats of a new cholecystokinin (CCK) receptor antagonist developed in Japan, KSG-504, administered intraduodenally, on pancreatic exocrine secretion stimulated by exogenous CCK and intraduodenal casein. Intraduodenal administration of KSG-504 in graded doses of 2.5-50 mg/kg/h produced dose-dependent inhibition of pancreatic juice volume and amylase output stimulated by intravenous infusion of CCK-8 in a dose of 0.06 micrograms/kg/h. The ID50 (half-maximal inhibition dose) of KSG-504 for CCK-8-stimulated amylase secretion was 3.4 mg/kg/h. Moreover, intraduodenal KSG-504 (5 and 25 mg/kg/h) dose dependently suppressed pancreatic juice volume, and amylase output increased with intraduodenal infusion of casein (400 mg/h). It is concluded that KSG-504 administered intraduodenally has a significant, potent inhibitory action on the exocrine pancreas stimulated by exogenous CCK and intraduodenal casein. PMID- 8190723 TI - Correlation between nucleolar organizer regions and cell proliferation in pancreatic acinar cell proliferative lesions in rats. AB - The numbers of nucleolar organizer regions (NORs) stained by the one-step silver (Ag) colloid method were measured in rat pancreatic basophilic foci, eosinophilic foci, and acinar cell adenomas induced by 4-hydroxyaminoquinoline 1-oxide (HAQO) followed by crude soybean trypsin inhibitor (SBTI) treatments and compared with values for bromodeoxyuridine (BrdU)-incorporating cells and nuclear DNA contents. Both numbers of AgNORs and BrdU-labeling indices showed stepwise increases from normal pancreatic acinar cells through eosinophilic foci to adenomas, and a good correlation was found between cell proliferation and mean numbers of AgNORs. Microspectrometry of nuclear DNA contents revealed a wide range of values in basophilic and eosinophilic foci and acinar cell adenomas as compared with normal acinar cells, but there was no significant difference in the profile of DNA content among these three proliferative lesions. The present results suggest that mean numbers of AgNORs may reflect cellular kinetics in rat pancreatic acinar cell lesions. PMID- 8190725 TI - Potentiation of canine pancreatic bicarbonate output by oleic acid is not neurally dependent. AB - To study neural involvement in potentiation of acid-induced pancreatic bicarbonate output, six dogs underwent extrapancreatic denervation and pancreatic fistula creation. Pancreatic responses to secretin (16 and 32 ng/kg/h) and cholecystokinin (50 ng/kg/h) were then assessed. The duodenum was then perfused with three sets of perfusates. The first set contained hydrochloric acid with either D- or L-phenylalanine. The second set contained bovine serum albumin and hydrochloric acid with or without oleic acid; the albumin and acid were varied so that each 50 ml contained 1, 2, or 4 meq titratable acid (pH 2.0-4.5). The third set was identical to the second except for initial pH of 3.5. Pancreatic responses predicted upon addition of cholecystokinin to secretin, L-phenylalanine to hydrochloric acid, or oleic acid to bovine serum albumin were compared with observed responses. At both doses, secretin-induced bicarbonate output was increased by cholecystokinin (16 ng/kg/h: 0.88 +/- 0.29 meq/15 min; 32 ng/kg/h: 1.01 +/- 0.23 meq/15 min). The latter significantly exceeded predicted output (16 ng/kg/h: 0.38 +/- 0.10 meq/15 min; 32 ng/kg/h: 0.58 +/- 0.15 meq/15 min), verifying potentiation. L-phenylalanine failed to potentiate bicarbonate output evoked by acidified D-phenylalanine. In contrast, addition of oleic acid to pH 2.0 or 3.5 bovine serum albumin potentiated bicarbonate output. These data suggest that enteropancreatic reflexes mediate potentiation of acid-induced pancreatic bicarbonate output by amino acids, but not by fatty acids. PMID- 8190726 TI - No parallel between the biochemical course of acute pancreatitis and morphologic findings. AB - The clinical, biochemical (serum enzymes), and morphologic course of acute pancreatitis was studied in 83 consecutive patients from time of admission until 3 months after discharge. At discharge, all 75 surviving patients had no more symptoms of acute pancreatitis, even though amylase (in 11%) and lipase (in 25%) were still elevated, computed tomography (CT) findings still abnormal (in 81%), and necrosis amounting up to 50% of the gland still present (in 24%). There was no significant correlation between serum enzymes and CT findings at discharge. Three months later, with the exception of one patient with an acute relapse of the disease, all followed-up patients were free of symptoms and had normal serum amylase, whereas lipase was still elevated in 10%, and CT findings abnormal in 23%. Subsiding symptoms provided a more accurate picture of the patients' recovery than the biochemical markers, and even more so that the morphologic findings. PMID- 8190727 TI - Ultrastructural study of the effects of stress on the pancreas in rats. AB - We studied morphologic changes in a rat model of acute hemorrhagic pancreatitis in order to investigate the mechanism by which water immersion stress injures the pancreas. Acute hemorrhagic pancreatitis was induced by two intraperitoneal injections of 40 micrograms/kg body weight of caerulein at 1-h intervals under water immersion stress for 5 h at 23 degrees C. Light microscopy showed interstitial edema with inflammatory cell infiltration, degeneration and necrosis of acinar cells, and bleeding. Electron microscopy showed large autophagic vacuoles, decreased zymogen granules, and dilated rough endoplasmic reticulum in acinar cells. Basolateral exocytosis of large vacuoles and phagocytosis of the degenerated acinar cells were observed. In addition, microvascular damage, including the destruction of the capillary endothelial cells, capillary thrombosis, and the extravasation of blood cells, was seen. In contrast, in a pancreatitis model induced by caerulein injection alone, there was no bleeding, no remarkable vascular change, and no thrombosis. Degeneration and necrosis of acinar cells were less severe. In the pancreas under stress alone, microvascular damage and degeneration of acinar cells were observed. These findings demonstrate that stress injures the pancreas and worsens the pancreatitis by causing microcirculatory disturbances, such as vascular damage, thrombosis, increased vascular permeability, and bleeding. These results suggest that chemical mediators, such as free radicals and platelet-activating factor (PAF), which are produced by vascular damage and thrombosis, may accelerate the activation of zymogen proteases in acinar cells in caerulein-induced pancreatitis, leading to hemorrhagic pancreatitis. PMID- 8190728 TI - High-resolution 1H NMR study of membrane phospholipids in rat pancreas stimulated by caerulein. AB - In this study, the peak observed at 3.2 +/- 0.2 ppm in the 1H nuclear magnetic resonance (NMR) spectra recorded at 60 MHz of rat pancreas stimulated by caerulein was characterized at higher resolution (100 and 300 MHz). Whole pancreas from rats stimulated by caerulein was analyzed ex vivo by 1H NMR spectroscopy at 100 MHz. After suppression of the tissue water peak (OSIRIS method), a peak at 3.2 +/- 0.2 ppm appeared distinctly, along with two other weaker signals (2.8 and 3.5 ppm). No signals were observed in these regions in the spectra recorded from pancreas of 48-h fasted rats. The signal at 3.2 +/- 0.2 ppm was characterized by analysis of the high-resolution 1H NMR (300 MHz) spectra of lipid extracts of rat pancreas. Addition of various pure membrane phospholipids in extracts showed that the peak was due to the N(CH3)3 groups of choline-containing lipids. The weaker signals (2.8 and 3.5 ppm) were attributed to the methylene protons of fatty acids and the glycerol of glycerophosphorylcholine (GPC). A small decrease in phosphatidylcholine (PC) concentration was observed on analysis of these lipid extracts by high performance liquid chromatography, indicating that the increase in intensity of the 3.2 +/- 0.2 ppm peak was not due to any increase in PC concentration, but rather to a change in conformation of PC, allowing higher mobility of the trimethylamino protons. Lorglumide, a specific inhibitor of caerulein, markedly reduced the intensity of the NMR peak, and pentagastrin, which also stimulates exocytosis of zymogen granules in the pancreas, had a similar but somewhat smaller effect than caerulein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190729 TI - Role of zinc in the process of pancreatic fibrosis in chronic alcoholic pancreatitis. AB - Zinc acts as a cofactor in many enzymatic processes, including collagen synthesis. The observation of increased activity of prolylhydroxylase (PHase), an enzyme that takes part in the synthesis of collagen, in zinc-depleted liver tissue suggests that zinc deficiency is associated with hepatic collagen deposition. The pancreatic zinc content in chronic alcoholic pancreatitis (CAP) is still unknown. The objectives of this study were (a) To assess zinc concentrations in the pancreatic tissue in CAP; (b) to establish a possible relation between pancreatic zinc content, fibrosis, and PHase activity; and (c) to evaluate the relation between serum and pancreatic zinc levels. Sixteen surgical specimens of pancreatic tissue from patients with CAP were analyzed; control pancreatic samples from 11 organ donors were also studied. Zinc concentration, PHase activity, and the amount of fibrous tissue were assessed in the pancreatic tissue of each individual. The amount of fiber deposited in the pancreas in CAP was 68.4 +/- 19.8%, and that of the control group, 5 +/- 2% (p < 0.001). PHase activity in CAP was 754 +/- 230 cpm/mg of protein and that of the control group was 405 +/- 151 cpm/mg of protein (p < 0.001). The amount of pancreatic zinc in the former was 15.0 +/- 9.7 micrograms/g of tissue and that of the latter was 28.1 +/- 18.1 micrograms/g of tissue (p = 0.023). Serum zinc levels were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190730 TI - Importance of diacylglycerol in glycerolipid biosynthesis by spinach chloroplast envelope membranes. PMID- 8190731 TI - The role of lipids in the structure and function of photosynthetic membranes. PMID- 8190732 TI - Special roles of inositol lipids in cell signaling and metabolic regulation. PMID- 8190733 TI - Accessible and exploitable diversity for oilseed breeding. PMID- 8190735 TI - Petroselinic acid biosynthesis and production in transgenic plants. PMID- 8190734 TI - New sunflower mutants with altered seed fatty acid composition. PMID- 8190736 TI - Plant lipases and their application in lipid biotransformations. PMID- 8190737 TI - Genetic resistance to disease and abiotic factors of genetically modified crops. PMID- 8190738 TI - Oleaginous fungi: carotene-rich oil from Phycomyces. PMID- 8190739 TI - High resolution 13C NMR. A technique for the study of lipid structure and composition. PMID- 8190740 TI - Environmental factors which can alter lipid metabolism. PMID- 8190741 TI - Characterization of virgin olive oils by SEXIA Expert System. PMID- 8190742 TI - The initial reactions of fatty acid biosynthesis in plants. PMID- 8190743 TI - Biosynthesis of very long chain fatty acids in higher plants. PMID- 8190744 TI - Biogenesis, function, and biotechnology of plant storage lipids. PMID- 8190745 TI - Factors controlling medium-chain fatty acid synthesis in plastids from Cuphea embryos. PMID- 8190746 TI - Silver ion and chiral chromatography in the analysis of triacylglycerols. PMID- 8190747 TI - Lipid photosynthesis in olive fruit. PMID- 8190748 TI - Human growth hormone. AB - The study of human growth hormone is a little more than 100 years old. Growth hormone, first identified for its dramatic effect on longitudinal growth, is now known to exert generalized effects on protein, lipid, and carbohydrate metabolism. Additional roles for growth hormone in human physiology are likely to be discovered in the areas of sleep research and reproduction. Furthermore, there is some indication that growth hormone also may be involved in the regulation of immune function, mental well-being, and the aging process. Recombinant DNA technology has provided an abundant and safe, albeit expensive, supply of human growth hormone for human use, but the pharmacological properties of growth hormone are poor. Most growth hormone-deficient individuals exhibit a secretory defect rather than a primary defect in growth hormone production, however, and advances in our understanding of the neuroendocrine regulation of growth hormone secretion have established the basis for the use of drugs to stimulate release of endogenously synthesized growth hormone. This promises to be an important area for future drug development. PMID- 8190749 TI - Update: pharmacology of airway secretion. PMID- 8190750 TI - Perspectives in receptor-mediated mineralocorticoid hormone action. PMID- 8190751 TI - Low molecular weight heparin: a critical analysis of clinical trials. AB - LMWHs are an important new class of antithrombotic agents. They differ from UFH in having relatively more anti-Xa activity, greater bioavailability at low doses, longer half-life, and more predictable anticoagulant response when administered in fixed doses. These properties allow LMWHs to be administered QD or at most BID and without laboratory monitoring. The incidence of heparin-induced thrombocytopenia also appears to be lower with an LMWH than with heparin. Given their favorable pharmacological profile, it was of interest to critically appraise clinical trials of thromboprophylaxis and treatment with these new agents. In orthopedic trials, it was noted that LMWH provided safe and effective thromboprophylaxis for patients undergoing major orthopedic surgery of the lower limb. In those having hip arthroplasty, LMWH was as effective as low-intensity warfarin therapy, but its use was associated with more wound hematomas. In those having total knee arthroplasty, LMWH was more effective than warfarin and did not increase bleeding. However, the prevalence of DVTs complicating this procedure as well as acute hip fracture remains unacceptably high, and additional studies of LMWH in combination with other prophylactic methods, such as external pneumatic compression, are needed. Only one adequately designed trial found less bleeding resulted from LMWH prophylaxis administered at an equivalent antithrombotic dose to UFH. In general medical patients, LMWH appeared to be as effective as UFH and had the advantages of less frequent injections and fewer injection site hematomas. In general surgical patients, there was a lower risk of thromboembolism but a trend toward an increase in bleeding events. Subjects with strokes and spinal cord injuries benefited from fewer thrombotic events, and the latter had fewer bleeding complications. Other potential indications for LMWH, such as cardiopulmonary bypass, hemodialysis, and preservation of graft patency, are presently under study. Perhaps the most impressive benefits of LMWH will be realized when it is used for the treatment of venous thromboembolism. The meta analysis presented in this review showed a trend toward greater efficacy with LMWH and fewer major bleeding events in comparison with adjusted-dose intravenous UFH. Also, during the months following the thrombotic event, there was significantly less mortality in patients receiving LMWH. A further advantage was the subcutaneous route of administration and lack of requirement for laboratory monitoring. Additional treatment trials are presently in progress and may establish LMWH as the treatment of choice for patients with thromboembolic disorders. PMID- 8190752 TI - A new gustometer for testing taste discrimination in the monkey. AB - A fully automated, 10-channel gustometer for use with nonhuman primates is described. The system, constructed primarily from commercially available components, includes an intelligence panel (containing sample spout, reward spout, and two operant response keys) that attaches to the door of a standard primate cage. The novel feature of the gustometer is a sample delivery spout that can be flushed, rinsed, and refilled within a specially designed rinsing chamber. All wetted surfaces of the gustometer are either Teflon, glass, or stainless steel. Flame photometric analysis confirmed the absence of cross-contamination between trials. Behavioral data collected from one rhesus monkey using a shock suppression procedure demonstrates the detection threshold for sodium chloride. Improvements to the design, including the addition of pressurized sample delivery triggered by a lickometer circuit, are discussed. PMID- 8190753 TI - The abnormal quinine drinking aversion in the Brattleboro rat with diabetes insipidus is reversed by the vasopressin agonist DDAVP: a possible role for vasopressin in the motivation to drink. AB - The Brattleboro rat with hypothalamic diabetes insipidus (BDI) has an abnormal aversion to drinking quinine-adulterated water compared with normal rats of the parent Long Evans (LE) strain. This BDI animal tolerates marked hypovolemia and decreased body weight in preference to drinking the quinine-adulterated fluid, indicative of a reduced motivation to drink. Acute or chronic treatment of BDI rats with desamino-8D arginine vasopressin (DDAVP) restored to normal their drinking response to quinine solution. Partial restoration of fluid turnover in BDI rats with hydrochlorothiazide, which has an antidiuretic effect in diabetes insipidus (when vasopressin is absent), failed to abolish the abnormal drinking response to quinine-adulterated solution in 8 out of 12 animals. In contrast, induction of diabetes mellitus in LE rats, which resulted in a marked polydipsia and polyuria even though vasopressin was still present, did not impair the drinking response to quinine solutions. These results suggest that the abnormal drinking response to quinine-adulterated fluid in BDI rats is reversed by treatment with the vasopressin V2-receptor agonist DDAVP but is unlikely to be a consequence of the restoration of fluid turnover to normal levels by a renal action. A possible central action involving vasopressin and the motivation to drink is discussed. PMID- 8190754 TI - Effect of hypoxia and exercise on the distribution of 65Zn in rat muscles. AB - The aim of this study was to determine the influence of hypoxia and exercise in 65Zn distribution in various rat muscles. A total of 80 male wistar rats weighting 250 +/- 10 g were randomly separated into eight groups: four groups in air, two at rest, and the other two after exercise; four groups in hypoxia (3 days exposure), two at rest, and the other two after exercise. Two groups (n = 10) in air and two other groups under hypoxia were injected with 65Zn. The 65Zn uptake by blood, pH, and PaO2 decreased significantly during hypoxia. The Zn concentration increased significantly in serum, diaphragm, gastrocnemius, and heart Zn after exercise in air. After hypoxia, at res, Zn increased in serum and in diaphragm. After chronic hypoxia, at rest, radioactivity of 65Zn increased in heart, gastrocnemius, and bone, and it was similar in air condition after exercise with respect to rest. In both cases (air and hypoxia), the uptake of 65Zn by the tissues was higher at rest. After exercise in hypoxia, endogenous Zn decreased in heart and in diaphragm. PMID- 8190755 TI - Effects of fat content, weight, and acceptability of the meal on postlunch changes in mood, performance, and cardiovascular function. AB - This study examined the effects of fat content and meal size on postlunch changes in mood, performance, and cardiovascular function. Forty-six subjects (20 males, 26 females) were tested before and after lunch. Subjects were assigned to one of the following lunch conditions: a) low fat (23 g), large meal (860 g); b) low fat (18 g), small meal (600 g); c) high fat (84 g), large meal (840 g); d) high fat (79 g), small meal (530 g). The results showed only small effects of fat composition and meal size, with no cardiovascular effects being observed and no evidence of fat content or the weight of the meal influencing performance of logical reasoning or cognitive vigilance tasks. A few effects of meal type were significant in the mood data, but given the large number of analyses conducted, these could represent chance effects. Results from two selective attention tasks showed that subjects given the high-fat meals responded more slowly but more accurately, which differs from the effects of carbohydrate, protein, and calorie content reported in earlier papers. Weight of the meal influenced the degree of distraction from near and far distractors and also the accuracy of responses to central and peripheral targets. However, both the effects of fat and meal size were modified by task parameters, and further research is required before firm conclusions can be drawn about the functional importance of the influences of nutrient content and meal size on performance. The high-fat and large meals were rated as more acceptable than the low-fat and small meals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190756 TI - Synergist interaction between angiotensin II and DOCA on sodium and water balance in rats. AB - Blockade of central angiotensin receptors with the specific antagonist [Leu8]-ANG II abolished water ingestion and water and sodium excretion induced by infusion of angiotensin II (ANGII) into the lateral ventricle (LV) of rats. The antagonist reduced but did not suppress the salt appetite induced by ANGII infusion. Subcutaneous injection of deoxycorticosterone acetate (DOCA) caused increases in water and 3% NaCl ingestion and decreases in sodium excretion. When central ANGII infusion was combined with peripheral DOCA, the water intake was similar to that induced by ANGII alone and the ingestion of 3% NaCl was increased, whereas sodium excretion was inhibited. When ANGII was infused alone, a detailed temporal analysis of fluid and sodium balance showed a negative balance similar those saline controls that persisted throughout the experiment. Combined administration of ANGII and DOCA induce significant changes in water and sodium balance. Sodium and water maintained a positive balance through out the 8-h experiment. The data support an interaction of central ANGII and DOCA on sodium intake and water and sodium balance. PMID- 8190757 TI - Food aversion conditioned in anesthetized sheep. AB - We discovered that a food aversion could be conditioned in anesthetized sheep. Sheep were allowed to eat a familiar food (alfalfa-grain pellets) for 30 min, and 90 min later they were given either an intraruminal (IR) injection of water (C), an IR injection of LiCl (L), anesthesia followed by an IR injection of water (A), or anesthesia followed by an IR injection of LiCl (A+L). Induction of anesthesia was by an intravenous injection of pentobarbitone sodium, and maintenance of deep anesthesia was by halothane. Sheep were maintained in deep anesthesia for 2 h to ensure that the effects of LiCl on the acquisition of a food aversion, which occur within about 1 h, were completed before they awakened. When tested 5 days later, sheep that received LiCl (treatments L and A+L) consumed less alfalfa grain pellets than sheep that did not receive LiCl (treatments C and A) (241 g vs. 306 g; p = 0.057). Intake of sheep that were anesthetized (treatments A and A+L) did not differ from that of sheep that were not anesthetized (treatments C and L) (295 g vs. 252 g; p = 0.183). Nor was there an interaction between LiCl and anesthesia (p = 0.423). Thus, we conclude that changes in preferences for foods caused by postingestive feedback occur automatically every time food is ingested (i.e., they are noncognitive), and the kind and amount of feedback is a function of the match between the food's chemical characteristics and its ability to meet the animal's current demands for nutrients. PMID- 8190758 TI - Open field, learned helplessness, conditioned defensive burying, and forced-swim tests in WKY rats. AB - Wistar Kyoto (WKY) and Wistar rats were observed in four tests; the open field test (OFT), the conditioned defensive burying (DB) test, and two tests which are considered animal models of depressive behavior, namely the Porsolt forced-swim test (FST) and the shuttlebox escape responding following exposure to inescapable shock, that is, learned helplessness (LH). The four tests were administered according to a semirandomized schedule to control for sequence effects. All rats were later exposed to water-restraint stress and stomachs were subsequently inspected for ulcers. Stress ulcer severity was greater in WKY rats. WKY rats, as compared to Wistar rats, were hypoactive in the OFT, did not engage in DB, rapidly acquired the LH task, and were significantly more immobile in the FST. The FST was positively correlated with behaviors in the LH procedure and, to a lesser degree, with DB, but these relationships were observed only with WKY rats, not Wistar rats. The data suggested that the use of WKY rats represented a more sensitive procedure for detecting possible relationships between putative animal models of depressive behavior. PMID- 8190759 TI - Effects of methamphetamine and methylphenidate on single and paired rat open field behaviors. AB - The present study used a video analysis system to investigate the effects of indirect dopamine agonists, methamphetamine and methylphenidate, on single and paired rat open-field behaviors. Experimental rats were injected with saline, methamphetamine, or methylphenidate (0.008, 0.04, 0.2, 1.0, 5.0 mg/kg, IP) and put into an open field for 30 min singly or paired with another rat. The rats' movements were plotted on XY coordinates by a video analysis system every 0.5 s and analyzed by distance and time factors. When paired, the experimental rats moved more than when single, and the total move distance increased according to dose of methamphetamine or methylphenidate. Further analysis showed that under methamphetamine, fleeing distances increased significantly but chasing distances were not affected; under methylphenidate, fleeing distances also increased, but chasing distances decreased significantly. Although two rats in an open field often stand in contact with each other, both methamphetamine and methylphenidate in doses exceeding 1.0 mg/kg tended to keep the two rats separate. These phenomena indicate that the two indirect dopamine agonists induce less interaction and decrease social behavior. PMID- 8190760 TI - Impairment of cognitive performance associated with dieting and high levels of dietary restraint. AB - Seventy women students were tested on a short battery of tasks assessing cognitive performance. They also completed self-report ratings of mood, the Dutch Eating Behaviour Questionnaire (DEBQ) to which was appended several additional items concerning their recent dieting behaviour, and a 24-h dietary recall. Heart rate was measured before and after testing. Compared with nondieting subjects with low to moderate scores on the restraint factor of the DEBQ, subjects (n = 15) who reported that they were currently dieting to lose weight displayed impaired performance on a vigilance task and also tended to show poorer immediate memory and longer reaction times. Highly restrained eaters who were not dieting at the time of testing, on the whole, performed at an intermediate level on these tests. In contrast, the dieters tended to show the best performance on an undemanding finger tapping task, indicating that they were not slowed in their fine motor responses or lacking in motivation to carry out the tasks. Poorer cognitive functioning during dieting could arise as a direct consequence of the effects of food restriction on energy metabolism or other physiological mechanisms--the dietary records indicated that the current dieters were eating at about 70% of maintenance energy requirement. However, it is also possible that cognitive performance is impaired during dieting due to anxiety resulting from stressful effects of imposing and maintaining dietary restraint. PMID- 8190761 TI - Aromatase-immunoreactive cells in the quail brain: effects of testosterone and sex dimorphism. AB - We previously demonstrated that testosterone (T) increases aromatase activity (AA) and that AA is sexually dimorphic (males > females) in the quail preoptic area (POA). The precise anatomical localization of these effects is, however, impossible to obtain by biochemical assays even when samples are dissected by the Palkovits punch technique. We were recently able to set up an immunocytochemical (ICC) procedure that permits visualization of aromatase-immunoreactive (ARO-ir) cells in the quail brain. This showed that the ARO-ir cells of the quail POA actually outline the sexually dimorphic medial preoptic nucleus (POM). This ICC technique was used here to analyze the sex dimorphism of the quail preoptic aromatase and the localization of T effects on ARO-ir cells. In Experiment 1, the number of ARO-ir cells was counted in one section every 100 microns throughout the rostral to caudal extent of the POM of castrated birds that had been treated with increasing doses of T (5, 10, or 20 mm long Silastic implants). These T treatments produced a dose-related increase in the sexual behavior of the birds and they increased the number of ARO-ir cells in POM, in the septal regions, and in the bed nucleus of the stria terminalis (BNST). The effect had a particularly large amplitude in the part of the POM located under the anterior commissure (AC). In Experiment 2, the same procedure was used to reanalyze the sex difference of the preoptic aromatase system. This showed that the POM of adult males contains more stained cells than the POM of females but only in a restricted region located just under and rostral to the AC. No significant sex difference was observed in the septum or in the BNST. In Experiment 3, the number of ARO-ir cells was determined in the POM of males and females that had been gonadectomized and treated with a same dose of T (40 mm implants). No sex difference in the number of ARO-ir cells could be detected in these conditions. This suggests that the sex difference in AA that had been previously observed in T-treated birds results either from a difference in aromatase concentration or activity in a similar number of positive cells or from a difference in the number of ARO-ir cells that is very discrete from the anatomical point of view.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8190762 TI - Magnetic field effects on spatial discrimination learning in mice. AB - A magnetic sense has been demonstrated in several species, including mice. It has been suggested that the basis of this sense, and its role in navigation, rests on the existence of ferromagnetic materials in the brain. Several researchers have shown changes in navigation during exposure to relatively weak magnetic fields, which presumably interact with magnetite in the brain. In this study, mice were exposed to the powerful magnetic field of an MRI scanner and their left-right discrimination learning was compared with a control group. Results indicate a significant decrement in such learning ability immediately after exposure. Suggestions for future research are presented. PMID- 8190763 TI - Altered catecholaminergic behavioral and hormonal responses in rats following early postnatal hypoxia. AB - We have previously reported alterations in a battery of behavioral functions in the rat following both intermittent and chronic prenatal hypoxia. In this species, the critical brain growth spurt for the catecholaminergic neurotransmitter system takes place in the late gestational and early postnatal period. In addition, postnatal stress can modify adult hypothalamic-pituitary adrenal responsiveness. Following a given stress, administration of dopaminergic/adrenergic agonists/antagonists may elucidate subtle changes that are not apparent in routine behavioral and endocrine tests. To test the hypothesis that early postnatal hypoxia affects development of the catecholaminergic system and, thus, alters functional outcome, we performed the following study. We exposed 25 litters of Sprague-Dawley rats, each consisting of 10 male pups, to hypoxia (10.5% inspired O2) for 6 h/day (0900 to 1500 h) from postnatal day (P) 2 to 10. We also had 25 control (C) litters. We then performed a series of behavioral tests in immature and mature animals. Body weights were significantly decreased in hypoxic (H) animals from P10 to P100. At P21 we tested locomotor activity in an open-field paradigm with drug challenge (apomorphine, a dopamine receptor agonist, 0.025 and 0.1 mg/kg; or haloperidol, a dopamine receptor antagonist, 0.2 and 0.4 mg/kg). Grooming activity was significantly decreased in H animals at both apomorphine concentrations, compared to controls. Moreover, rearing activity was significantly increased in H animals under basal conditions and when challenged with 0.1 mg/kg apomorphine. Apomorphine (1.0 mg/kg)-induced stereotypy at P39 was significantly increased in H animals compared to controls. Open-field activity at 80 days revealed no significant differences in drug responsiveness between H and C animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190764 TI - Taste preference of Old World monkeys: I. A single-bottle preference test. AB - There have been relatively few published reports of the taste preferences of nonhuman primates due, in part, to the expense and relative difficulty associated with maintaining a large group of these animals. The present report describes a version of the single-bottle preference test that can be used effectively with small groups of macaque monkeys. Experiment 1 determined the optimal durations for the pretest water deprivation period, the test trial itself, and the posttest rehydration period. Experiment 2 used this procedure to examine intake of the four prototypical gustatory stimuli. The results showed that cynomolgus monkeys, like other species, accept solutions containing sucrose and isotomic saline and reject those containing quinine hydrochloride. Unlike most other species, however, these monkeys do not find moderate concentrations of hydrochloric acid aversive. PMID- 8190765 TI - Energy balance in an inbred strain of rats: comparison with the Wistar strain. AB - Food intake and body weight gain were examined in two groups of male rats (7 weeks): an inbred strain, Dark Agouti (DA, n = 12) and a noninbred strain, Wistar (n = 13). The animals were allowed to select their diet from separate sources of the three macronutrients protein, fat, and carbohydrate. After 10 days of adaptation to the diets, body weights and food intakes were measured for 3 weeks. During this period, meal patterns were recorded for at least 5 days in each rat. Then, rats were switched to a chow diet (UAR, A.O4) for 10 days. The total caloric intake of DA rats was 60% that of Wistar rats, while their body weight gain was 25% that of Wistar rats (1.3 g/day in DA vs. 5.3 g in Wistar). However, when energy intake was related to total body weight, there was no difference in energy ingestion. It was observed that DA rats ingested mainly proteins (45%) and fats (41%), while Wistar rats ingested an identical proportion of proteins and carbohydrates (40%). The percent of total white adipose tissue to total body weight was identical in both strains (6% on average). Brown adipose tissue thermogenic activity of DA rats was threefold higher than in Wistar rats. This could be one of the elements responsible for the lower body weight gain of this group of rats. Self-selected food intake of the inbred DA strain of rats, in contrast to what was expected, was greatly variable. PMID- 8190766 TI - Eating rates in normal and hypothalamic hyperphagic rats. AB - Two experiments were conducted to determine if hypothalamic hyperphagic rats eat at a faster than normal rate and if slowing the rate of eating would reduce their overeating. Experiment 1 used a 45 mg pellet eatometer to measure 24-h meal patterns and eating rates in control rats and rats made hyperphagic with medial hypothalamic (MH) knife cuts. The MH hyperphagic rats consumed larger and more frequent meals but ate at a slower rate than did control animals during both the dynamic and static phases of the syndrome. In Experiment 2, rats were given 30 min test meals with the same pellets presented in food cups (rather than one pellet at a time as with the eatometer). The MH rats consumed the pellets at the same rate as the controls, although their meals were twice as large. Experiment 1 also determined if slowing the rate of eating would reduce MH hyperphagia; eating rates were constrained by increasing the delay between successive pellet deliveries (normally < 1 s). An interpellet delay of 20 s reduced meal size and increased meal length and frequency but did not reliably reduce 24-h food intake in normal rats and dynamic or static phase MH rats. Interpellet delays of 40 or 60 s reduced daily food intake of static phase MH rats but only to control levels. These results indicate that MH hyperphagia is not associated with elevated feeding rates and is relatively unaffected by constraints on the rat's rate of eating. PMID- 8190767 TI - Age-dependent responses to chemosensory cues mediating kin recognition in dogs (Canis familiaris) AB - During individually administered 5-min tests conducted in a neutral cage, four age groups (n = 10 males and 10 females per group) of purebred beagles reacted to bedding from their home cage vs. bedding from another litter of the same age. The 20-24-day-old males and females preferred (p < 0.05) home cage bedding over strange cage bedding. Those aged 31-36 days or 66-72 days showed no reliable preference for either type of bedding. Among pups aged 52-56 days, the males preferred (p < 0.05) strange cage bedding, but the females showed no reliable preference. Chemosensory cues are sufficient as mediators of kin recognition in beagles, but their reactions to such cues vary with age-dependent factors, some stemming from changes in the strength of the mother-litter bond. The dogs providing the two types of bedding lived in the same room and on the same diet. Therefore, kin recognition could not have been mediated by different chemosensory cues produced by variations in these environmental factors. PMID- 8190768 TI - Dissociation of palatability and calorie effects in learned flavor preferences. AB - Rats acquire a preference for a flavor paired with a caloric solution over a flavor paired with a solution providing fewer or no calories. Because the palatability and the caloric value of the solutions typically covary, it is unclear which property of the high-calorie solution reinforces the flavor preference. Two studies were conducted to assess the independent effects of palatability and calories in flavor preference conditioning. In Experiment 1, rats consumed two distinctively flavored solutions having equal palatability but different caloric value. The flavor paired with ingestion of more calories was subsequently preferred, indicating that a caloric advantage is sufficient to establish a flavor preference (flavor-calorie conditioning). In Experiment 2, rats consumed two distinctively flavored solutions having equal calories but different palatability. The flavor paired with the more palatable solution was subsequently preferred, indicating that a palatability advantage is sufficient to establish a flavor preference (flavor-flavor conditioning). This finding demonstrates flavor-flavor conditioning in the context of postingestive stimulation by calories. Taken together, these results demonstrate both flavor calorie and flavor-flavor conditioning in the context of normal ingestion (i.e., self-paced oral intake of nutritive solutions). PMID- 8190769 TI - Parasite infection attenuates nonopioid mediated predator-induced analgesia in mice. AB - Parasites have been shown to have a broad range of effects on host behavior, including alterations of host responses to predators. Response to the threat of predation consist of a number of defensive behaviors, including a reduction in pain sensitivity and the induction of analgesia. The present study examined the relationships between subclinical (i.e., nonpathological) infection with the naturally occurring, enteric, sporozoan (coccidian) parasite, Eimeria vermiformis, predator exposure, and nociceptive responses in male mice. Brief (30 s) exposure of nonparasitized mice to a predator (a cat) induced marked, relatively short-lived analgesia that was insensitive to naloxone and blocked by the serotonin-1A (5-HT1A) agonist, 8-OH-DPAT. In contrast, mice acutely infected for 6 days with E. vermiformis, failed to show a predator-induced analgesia. The parasitized mice did display a naloxone-sensitive hypoalgesia or analgesia. However, restraint-stressed mice, which displayed a naloxone-sensitive hypoalgesia similar in amplitude to that of the infected mice, still exhibited a nonopioid mediated, predator-induced analgesia. These observations indicate that parasite infection attenuates 5-HT1A-sensitive predator-induced analgesia and likely reduces the accompanying fear and anxiety related anticipatory defense reactions of the host to the predator. PMID- 8190770 TI - Conditioned control of ingestive behavior by acarbose-induced inhibition of sucrose ingestion in the rat. AB - It has been reported that the addition of Acarbose, a alpha-glucosidase inhibitor, to a carbohydrate solution blocks a preference that otherwise would be displayed for that solution. One interpretation of those results is that the alteration in preference was caused by the diminished postabsorptive nutritive value of the diet due to the inhibition of hydrolysis of the carbohydrates, and, thus, its absorption. An alternative explanation is that the reduction in the preference was a consequence of an accumulation of undigested carbohydrates in the lumen of the intestine. In the studies reported here, designed to investigate this alternative explanation, it was shown that Acarbose added to a flavored 0.3 M sucrose solution reduced the preference for that solution in a two-bottle preference test. An analysis of the licking behavior of rats ingesting flavored 0.3 M sucrose solutions with and without the addition of Acarbose revealed that the presence of Acarbose in the test solution caused a conditioned reduction in the rate of licking the test solution at the beginning of the meal and, as a result, a reduction in intake of the solution. This conditioned control of the rate of licking was rapidly acquired and was easily reversed. It was also shown that Acarbose increased fluid retention in the small intestine, suggesting that the conditioning may have been based on the accumulation of undigested disaccharides in the intestinal lumen rather than on the diminished postabsorptive nutritive value of the ingested sucrose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190771 TI - Inhibition of sexual maturation in juvenile female and male mice by a chemosignal of female origin. AB - Maturation of juvenile house mice (Mus domesticus) exposed to synthetic 2,5 dimethylpyrazine was compared to the maturation of juvenile male and female mice exposed to urine from adult males and grouped females. Exposure of juvenile male mice to the synthetic compound significantly inhibited the growth of their testes and sex-accessory glands in a fashion similar to the urine of adult males and grouped females. The uterine weight and the presence of ova in the oviducts in females was strongly affected by synthetic stimuli. The majority of females (76 84%) exposed either to grouped females' urine or to the synthetic compound did not exhibit significant uterine weight increase and did not achieve pubertal ovulation before the age of 30 days as it has been reported for control mice. It is suggested that 2,5-dimethylpyrazine delays puberty of juvenile conspecifics in a population and may function whenever the living conditions of growing animals are below the level required for successful reproduction. PMID- 8190772 TI - Effects of administration of branched-chain amino acids vs. glucose during acute exercise in the rat. AB - Several studies of the relationship of food intake to physical exercise strongly suggest that the two are closely linked. Serotonin transmission seems to be particularly important in the regulation of both appetite and central fatigue. Thus, the ingestion of branched-chain amino acids has been reported to decrease serotonin production and to improve physical performance. In the present study, the effects of three treatments (water, glucose, and branched-chain amino acids) were compared in 34 male Wistar rats. Maximal exercise duration, blood insulin, and glucose levels were measured. Results showed that following the ingestion of branched-chain amino acids, physical performance is lower and blood insulin level is higher than after glucose administration. PMID- 8190773 TI - Experience modulates the influence of gonadal hormones on sexual orientation of male rats. AB - The aim of this study was to investigate whether heterosexual experience influences the male's partner preference and the role of gonadal hormones, including several androgens and estradiol, on female-oriented behavior. In the first experiment, the animals were exposed to a four-stimuli test situation including a sexually active male, a castrated male, an estrous female, and an ovariectomized (ovx) female. Castrated naive and experienced male rats were implanted with either testosterone (T), estradiol (E2), or an empty tubing (blank) and compared to intact naive and experienced male rats. None of the naive animals, whether castrated or intact, showed a consistent preference for any of the four stimuli. Whereas when sexually experienced, only intact and T-treated males showed a female-oriented preference. In the second experiment, the animals were allowed to choose between an active male and an estrous female. Castrated naive male rats were implanted with either T, E2, or DHT, or injected daily SC with the synthetic nonaromatizable androgen, methyltrienelone (R 1881). Two groups of intact males, one consisting of experienced and the other of naive animals, were also included in this experiment. The experienced intact males showed a significant preference for the estrous female, while the intact naive males showed no preference for either of the two stimuli. After the animals had gained heterosexual experience, intact and androgen-treated males showed a significant preference for the female. Neither the administration of R 1881 nor E2 promoted a female-oriented behavior.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190774 TI - Dissociation of androgen-dependent sociosexual behaviors in response to castration in Long-Evans rats. AB - Copulatory behavior and associated social behaviors such as ultrasonic vocalizations and scent marking are reduced in frequency following castration and are restored by exogenous administration of androgens. In the present study, we report the behavior of a subgroup of male Long-Evans rats in which there was a dissociation between the responses of androgen-dependent behaviors to castration. Five weeks after castration, 52% of the males tested (13 of 25) had higher 50 kHz vocalization frequencies than during precastration tests. This group continued to emit vocalizations after castration and actually increased their number of vocalizations over postcastration tests (pretest: 34.5 +/- 4.8 to week 15: 62.8 +/- 10.9/10 min test). The remaining males (n = 12) exhibited a decline in vocalizations (pretest: 29.7 +/- 5.1 to week 15: 6.5 +/- 2.7) that we typically observe in our laboratory. Both groups showed the expected decline in scent marking frequency over the postcastration tests and were impaired in performance of copulatory behavior. Seminal vesicle and adrenal gland weights did not differ between the two groups. The 25 males were of the same genetic strain as previous animals in our laboratory except that they were born and raised in a different location prior to shipment to our laboratory. Androgens, therefore, may be only one of the possible influences mediating ultrasonic vocalizations. PMID- 8190775 TI - Effect of rectal distention and feeding on cecal tone in pigs. AB - The effects of eating and rectal distention on cecal tone were evaluated. Cecal tone was measured using a computer-controlled barostat in four female 30 to 40 kg Yucatan Micropigs fitted with cecal fistulas. Each pig underwent two separate trials of pre and postprandial measurements of cecal tone, either with or without continuous rectal distention with a 30 ml water-filled balloon. Cecal tone was measured 10 min prior to, during, and 10 min following a high-fat (60%) liquid meal (473 ml). Cecal tone significantly increased (intrabag volume decreased) after feeding (119.6 +/- 9.1 ml vs. 81.2 +/- 7.9 ml; p = 0.008). Rectal distention tended to reduce the postprandial change in cecal tone (142.8 +/- 11.5 vs. 130.9 +/- 12.6 ml; p = 0.196). There was also a strong tendency for cecal volumes to be higher (decreased tone) with rectal distention preprandially (142.8 +/- 11.5 ml vs. 119.6 +/- 9.1 ml; p = 0.024). Nutrient ingestion significantly increased cecal tone and rectal distention abolished this effect. These findings may indicate a regulatory pathway that allows additional storage of fecal material in the event that the output of the system is disturbed. PMID- 8190776 TI - Adaptation of sweeteners in water and in tannic acid solutions. AB - Repeated exposure to a tastant often leads to a decrease in magnitude of the perceived intensity; this phenomenon is termed adaptation. The purpose of this study was to determine the degree of adaptation of the sweet response for a variety of sweeteners in water and in the presence of two levels of tannic acid. Sweetness intensity ratings were given by a trained panel for 14 sweeteners: three sugars (fructose, glucose, sucrose), two polyhydric alcohols (mannitol, sorbitol), two terpenoid glycosides (rebaudioside-A, stevioside), two dipeptide derivatives (alitame, aspartame), one sulfamate (sodium cyclamate), one protein (thaumatin), two N-sulfonyl amides (acesulfame-K, sodium saccharin), and one dihydrochalcone (neohesperidin dihydrochalcone). Panelists were given four isointense concentrations of each sweetener by itself and in the presence of two concentrations of tannic acid. Each sweetener concentration was tasted and rated four consecutive times with a 30 s interval between each taste and a 2 min interval between each concentration. Within a taste session, a series of concentrations of a given sweetener was presented in ascending order of magnitude. Adaptation was calculated as the decrease in intensity from the first to the fourth sample. The greatest adaptation in water solutions was found for acesulfame-K, Na saccharin, rebaudioside-A, and stevioside. This was followed by the dipeptide sweeteners, alitame and aspartame. The least adaptation occurred with the sugars, polyhydric alcohols, and neohesperidin dihydrochalcone. Adaptation was greater in tannic acid solutions than in water for six sweeteners. Adaptation of sweet taste may result from the desensitization of sweetener receptors analogous to the homologous desensitization found in the beta adrenergic system. PMID- 8190777 TI - Menstrual cycle and dietary restraint influence taste preferences in young women. AB - Previous reports indicate that some women increase their consumption of sugar and fat premenstrually. To ascertain whether this is due to differences in taste acuity for sweetness and fatness and/or preference across the menstrual cycle, 25 female and 12 male undergraduates rated the pleasantness, sweetness, and fatness of 16 taste stimuli made of dairy products with varied fat contents (0%, 3.5%, 10%, 36%) and sucrose (0%, 5%, 10%, 20%) over 4 consecutive weeks. There was a marked decline in ratings over the 4 weeks of testing. Taste preferences of women were not uniform across the menstrual cycle. Those who began testing during the luteal and menstrual weeks had increased preference ratings compared to those who began during the follicular or ovulatory weeks. Preference ratings for taste stimuli containing 0% and 5% sucrose were lower in women with higher scores on a restraint of eating scale, than for women with lower scores. No differences in sweetness or fatness ratings were observed across the menstrual cycle, or as a function of dietary restraint. Men had increased preference for taste stimuli containing 10% and 20% sucrose compared to women; however, no differences in ratings of either sweetness or fatness were found as a function of gender. These data indicate that taste preference in women is not homogeneous across the cycle. Instead, many factors, including the menstrual cycle and degree of eating restraint, influence preference ratings. PMID- 8190779 TI - Actions of sciatic nerve ligature on sexual behavior of sexually experienced and inexperienced male rats: effects of frontal pole decortication. AB - The action of the hyperalgesia produced by the loose ligature of the sciatic nerve on the sexual behavior of two groups of sexually experienced and inexperienced male rats was studied. The putative changes in the behavior induced by this manipulation were attempted to be counteracted by the removal of the anterior frontal cortex. Independently of the sexual experience, the ligature of the sciatic nerve did not modify any parameter of the sexual behavior, except for a slight prolongation of the intromission latency. Surprisingly, the removal of the cortical frontal pole resulted in drastic changes in the sexual behavior of sexually inexperienced male rats such as an increase in the intromission and ejaculation latencies and the postejaculatory interval. These changes were not observed in the sexually experienced group. Interestingly, the sciatic nerve ligature prevented the changes in the copulatory behavior produced by the frontal cortex removal. These results suggest that the hyperalgesia induced by the sciatic nerve ligature was unable to alter the sexual behavior. By contrast, the frontal cortex removal produced important changes in the sexual behavior that depend upon the previous sexual experience. All results are discussed on the bases of the neural control underlying the possible relationships between algesia and male sexual behavior. PMID- 8190778 TI - Hormonal control of response to and secretion of sex attractants in Japanese newts. AB - Hormonal control of sexual chemoattraction in the newt, Cynops pyrrhogaster, was investigated by a water preference test. Sexually inert newts injected with prolactin (PRL) and human chorionic gonadotropin (HCG) in combination preferred the water in which newts of the opposite sex had been kept, whereas saline injected specimens did not. This indicates that PRL and HCG enhance the response of the newts to attractant(s) secreted by the opposite sex. The water in which PRL plus HCG-treated newts had been kept attracted the opposite sex more intensely than the water in which PRL-, HCG-, or saline-injected newts had been kept. In castrated males, PRL plus testosterone propionate (TP), and in ovariectomized females, PRL plus estradiol induced the secretion of substance(s) that attracted newts of the opposite sex. Removal of the abdominal gland of the cloaca in the male or the oviduct in the female attenuated the attracting activity of the water in which they were kept. Involvement of PRL and gonadal steroids in the secretion of sex attractants by the male abdominal gland and female oviduct was suggested. PMID- 8190780 TI - Responses to cold, heat, and pain increase locomotion in rats and are attenuated by pinealectomy. AB - The effects of pinealectomy on locomotor behavior responses to cold, heat or pain were assessed in freely moving rats. External cold (4 degrees C) or heat (36 degrees C) stress produced increases of locomotion (including horizontal and vertical movement, and total distance traveled), increases of number of turnings (including both clockwise and counterclockwise), and decreases of postural freezing in rats. In addition, pain (produced by intradermal injection of normal saline) was also shown to produce increases of locomotion (including horizontal and vertical movement, and total distance traveled) and decreases of postural freezing in rats. The increases of locomotion (including horizontal and vertical movement, and total distance traveled), as well as the decreases of postural freezing induced by either cold or pain, were attenuated by pretreatment of animals with pinealectomy. The heat-induced increases of vertical movement as well as the decreases of postural freezing were also attenuated by pinealectomy. The results indicate that these nonphotic, stress-provoking stimuli act through the pineal gland to induce escape behaviors to try to get out of the stressed conditions in rats. PMID- 8190781 TI - Modification of acoustic and tactile startle by single microwave pulses. AB - Single microwave pulses at 1.25 GHz were delivered to the head and neck of male Long-Evans rats as a prestimulus to acoustic and tactile startle. For acoustic startle, pulses averaging 0.96 microsecond in duration were tested with two specific absorption rate (specific absorption) ranges, 15.0-30.0 kW/kg (16.0-44.2 mJ/kg) and 35.5-86.0 kW/kg (66.6-141.8 mJ/kg), delivered 201, 101, 51, 3, and 1 ms before and 1 ms after onset of a startling noise. The low-intensity pulse did not affect peak amplitude, integral, or latency of the whole-body startle response. The high-intensity pulse at 101 and 51 ms inhibited the startle response by decreasing peak amplitude and integral; at 201 and 51 ms latency was increased. The high-intensity pulse at 1 ms enhanced the startle response by increasing peak amplitude and at 3 ms by increasing integral. For tactile startle, either microwave pulses averaging 7.82 microseconds in duration and 55.9 113.3 kW/kg (525.0-1055.7 mJ/kg) or 94 dB SPL clicks were delivered 157, 107, 57, and 7 ms before and 43 ms after onset of a startling air burst. The microwave pulse at 57 ms inhibited the startle response by decreasing peak amplitude; at 157, 107, 57, and 7 ms it increased latency. The microwave pulse at 43 ms after onset enhanced the startle response by increasing peak amplitude. The acoustic click at 157 and 57 ms inhibited the startle response by decreasing peak amplitude; at 157,2 107, and 57 ms it increased latency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190782 TI - Latent inhibition of the rat eyeblink response: effect of hippocampal aspiration lesions. AB - The effect of hippocampal aspiration lesions on latent inhibition of eyeblink conditioning in the restrained rat preparation was examined. Rats received either sham, cortical control, or hippocampal aspiration lesions. Control animals, but not animals with hippocampal lesions, showed slower conditioning after being preexposed to the conditioned stimulus (latent inhibition). Together with previous results regarding the effect of hippocampal lesions in acquisition and extinction of delay conditioning, the present study suggests that the restrained rat preparation may serve as a reliable way of investigating hippocampal participation in different classical conditioning paradigms. PMID- 8190783 TI - Effect of race on perception of fat alone and in combination with sugar. AB - Two studies were performed to assess the perception of sugar-fat combinations and fat emulsions in African-American and white subjects. In the first study, African American children aged 9-15 years were found to prefer higher concentrations of sweetness in liquid dairy products varying in fat content than white children. No significant differences in preference for the four fat levels were found. These data are consistent with a previous study by Desor et al. (2) that suggested African-American youngsters aged 9-15 preferred greater sweetness in water solutions. In a second study, thresholds and preferences for corn oil and butterfat in emulsions were determined for young adults. No significant differences between African-American and white young adults were found. PMID- 8190784 TI - Maternal ingestion of tyrosine during rat pregnancy modifies the offspring behavioral lateralization. AB - It was previously reported that oral administration of tyrosine (500 mg/kg) to pregnant rats increases tyrosine and monoamines level in the fetal brain and modifies locomotion during postnatal life. In the present study, it was found that this treatment alters behavioral lateralization in the offspring. Neonatal rats whose mothers received tyrosine during the second half of gestation showed a low level of absolute and population laterality in both tail and head movements. The alteration of behavioral lateralization was also found during postnatal development and during adulthood. The T-maze behavioral ontogeny was different for tyrosine-mother and sham-treated or untreated mother rats. During adulthood, the T-max lateralization after stress sessions (a procedure that decreases alternation behavior and facilitates the quantification of behavioral lateralization) was also different in control and tyrosine-mother groups. Neonatal and adult rats showed an increase in right-side movements probability. These data provide evidence that maternal ingestion of a catecholamine precursor during gestation may induce a long-lasting modification of the behavioral lateralization of the offspring. PMID- 8190785 TI - Maternal behavior of female rats with 6-OHDA lesions in the ventral striatum: characterization of the pup retrieval deficit. AB - The present experiments characterized the impairment in pup retrieval previously observed in maternal rats following dopamine-depleting 6-hydroxydopamine (6-OHDA) infusions in the ventral striatum. Video recordings of 30-min pup retrieval tests revealed that 6-OHDA mothers spent most of the time feeding (Experiment 1). Denying the mothers the opportunity to eat during testing failed to reestablish pup retrieval. Similarly unsuccessful was an attempt to evoke food-motivated pup retrieving in 6-OHDA mothers by coating the stimulus pups' skin with a 4% sucrose solution (Experiment 2). However, restoration of pup retrieval was observed in 6 OHDA mothers that had been separated from their pups for 3-6 h (Experiments 3 and 4). Stimulation of ultrasonic callings by clonidine treatment of the stimulus pups, or leaving pups in the nest during testing, were not significantly effective (Experiment 3). These data suggest that separation-induced increases in maternal motivation can override the inhibitory effect of ventral striatal dopamine depletion on pup retrieval. PMID- 8190786 TI - Reduced content and preserved translocation of glucose transporter (GLUT 4) in white adipose tissue of obese mice. AB - We investigated glucose transporters (GLUT 1 and GLUT 4) in subcellular membrane fractions of white adipose tissue (WAT) of insulin-resistant obese aurothioglucose (AuTG)- or monosodium glutamate (MSG)-treated mice. In vivo insulin stimulation (0.75 U/kg, EV) promoted, 10 min later, no significant change on glycemia of both AuTG and MSG obese mice, but control mice showed a decrease of 30% (p < 0.001). Basal GLUT 4 content in WAT of obese mice was reduced by 40% (p < 0.001) when compared to that of nonobese mice. Insulin-stimulated GLUT 4 content was significantly (p < 0.01) higher in plasma membrane fraction and lower in microsomal fraction when compared to respective basal values, in all groups. Although the absolute values of GLUT 4 were lower in membrane fractions of obese mice, the relative changes stimulated by insulin were similar among the groups. No effect of obesity or insulin stimulation was observed upon GLUT 1 content. We conclude that WAT of insulin-resistant obese AuTG- and MSG-treated mice has a decreased GLUT 4, but not GLUT 1, content, and the in vivo insulin-stimulated GLUT 4 translocation is preserved. PMID- 8190787 TI - LTP of mossy fiber-stimulated potentials in CA3 during learning in rats. AB - The study was done to determine whether long-term potentiation (LTP) of the potentials occurs at mossy fiber (MF)-CA3 synapses with the advance of learning in unrestrained and unanesthetized rats. The rats were divided into two groups, the test and control groups. The test group was given daily learning tasks in the radial arm maze, whereas the control group was similarly handled without learning tasks. Complete acquisition of learning was observed in the test group on day 5, and the learning was maintained over 3 days. Under freely moving conditions, a significant increase in population spikes (PS) elicited by MF stimulation with the progress in learning was observed in the test group, and the PS potentiation remained stable after day 4. Furthermore, on day 7, when MF stimulation-induced PS in the test group were compared with that in the control group in pentobarbital-anesthetized rats, the responses were comparatively higher in the former. As the training-induced PS potentiation in CA3 occurred with the advance of learning, these findings suggest that LTP in CA3 induced by learning may be related to memory storage. PMID- 8190788 TI - Six differences in the locomotor-activating effects of amphetamine: role of circulating testosterone in adulthood. AB - The effects of circulating testosterone (T) on sex differences in locomotor activity elicited by both acute and repeated amphetamine (AMPH) administration were evaluated in adult rats. Male and female rats were gonadectomized in adulthood and implanted with Silastic capsules containing either T or cholesterol (CHOL). In the preexposure period, locomotor activity in response to IP injections of either AMPH (1.5 or 1.3 mg/kg) or saline (1.0 ml/kg) was measured for 2 h, every third day on five occasions. In a subsequent test for sensitization, all animals received AMPH (0.75 or 0.65 mg/kg). Results indicate that regardless of the presence of circulating T, females showed higher levels of activity in response to AMPH than males. In male animals, T suppressed AMPH induced activity on the first day of the preexposure period, but this effect was lost with repeated testing. In female animals, T enhanced AMPH-induced activity during the first hour of testing. The presence of circulating T did not influence the degree of sensitization in either sex as determined by the difference between AMPH preexposed and SAL preexposed animals on the test day for sensitization. PMID- 8190789 TI - Effects of time of day on dressing behavior under the influence of ambient temperature fall from 30 degrees C to 15 degrees C. AB - The present paper is aimed at determining whether the dressing behavior for temperature regulation in cold is under the influences of circadian control. The half-naked subjects were instructed to dress in the garments they felt comfortable when the room temperature began to decrease from 30 degrees C to 15 degrees C in 1 h. To determine the effects of brain temperature fall on the dressing behavior, we used face cooling with cool air for 30 min before the room temperature began to decrease. We also studied the effects of wearing a hat on dressing behavior. Rectal temperature, tympanic temperature, skin temperature at seven sites, and thermal sensation were recorded. Major findings are summarized as follows: 1) the subjects dressed faster with thicker clothing in the morning than in the evening; 2) the subjects with face cooling dressed faster with thicker clothing than the subjects without face cooling; 3) the subjects without a hat dressed more rapidly with thicker, heavier clothing. These results were discussed in terms of load error between actual and set-point values in the core temperature. PMID- 8190790 TI - Assessing pain threshold in the rat: changes with estrus and time of day. AB - Pain threshold was determined in female rats using the tail flick test. Latency to respond depended on the locus of the tail heated, with the most distal sites resulting in the shortest response times (Experiment 1). Tail flick latency also varied according to the time of day, with shorter response times recorded around the middle of the dark phase than near its beginning or after its end. This was the case for intact, for ovariectomized, and for ovariectomized, estradiol treated rats (Experiment 2). However, response times also varied across the estrous cycle, with significantly shorter latencies recorded during estrus and metestrus. Ovariectomy abolished these fluctuations, and whereas administration of estradiol increased response times, progesterone had little effect (Experiment 3). These results suggest that site of tail heating, time of day, and presence of ovarian hormones can influence tail flick latency independently, thus demonstrating the complexity of the mechanisms that may contribute to pain threshold even within the same paradigm. PMID- 8190791 TI - Effects of time-restricted access to protein and of oral-sensory cues on protein selection. AB - The effects on protein consumption of restricting access to protein and of varying the oral-sensory properties of protein diets were measured. During the initial phase of the study, rats were maintained on a self-selection diet in which three different macronutrient sources (carbohydrate, fat, and either soy based or casein-based protein diets) were continuously available. For the remaining 9 days of the study, half of the rats were protein deprived for 23 h each day and the other half continued to receive the same protein diet during this 23-h period. The remaining 1 h of each day was a test period in which all rats had access to a protein diet that was either the same as or different from the one they had received in the initial phase. Compared to the nonrestricted rats, the protein-restricted rats consumed diet during 1-h test periods. For the nonrestricted rats, those that received diet during 1-h test periods. For the nonrestricted rats, those that received a different protein diet during the 1-h test periods consumed 60% more of the protein diet than did those that received the same protein diet. These results indicate that increases in protein consumption following protein deprivation can be attributed, at least in part, to the oral-sensory properties of diets and not necessarily to a specific protein appetite. PMID- 8190792 TI - The effect of food deprivation on the reinforcing value of food and smoking in bulimic and control women. AB - The reinforcing value of both food and cigarettes was examined in female smokers with and without bulimia nervosa. Subjects underwent two food-deprivation (18 h) and two nondeprivation conditions and worked for either food vs. money or cigarettes vs. money on concurrent progressive variable ratio schedules. Schedules for food/cigarettes increased progressively while schedules for money remained the same. Results indicated no differences in the amount of time subjects spent working for food or the number of points earned for food in either bulimics or controls when examining the entire eight-game trial. Results of the initial two-game trial indicated marked differences, with the reinforcing value of food increasing after deprivation in control but not bulimic women and the total amount of time spent working for cigarettes increased after deprivation in controls. These results highlight that the effects of experimental food deprivation are most salient immediately after the deprivation and at low unit prices, and that bulimic and control women respond differently to a food deprivation paradigm. PMID- 8190793 TI - Long-term variations of arterial blood pressure during sleep in freely moving cats. AB - Using a new telemetric system for arterial blood pressure recordings, we have investigated long-term postoperative changes in blood pressure during sleep in freely moving cats. Particular attention was paid to the transitional periods at the beginning and end of paradoxical sleep (PS), as well as to the relationship between the blood pressure and ponto-geniculo-occipital (PGO) waves. In the initial postoperative stage lasting 2 to 5 days, the blood pressure decreased during the transition from slow wave sleep (SWS) to PS and maintained its lower level until the end of PS. In contrast, in the later chronic stage, the blood pressure increased tonically during the transition from SWS to PS and maintained its higher level throughout PS on which several phasic rises in blood pressure were superimposed. A significant increase in arterial pressure during the transitional period began shortly after the first appearance of PGO waves. On the other hand, significant phasic rises in arterial pressure during PS shortly preceded the onset of PGO wave bursts. PMID- 8190794 TI - Effect of a preferred companion in modulating stress in adult female rhesus monkeys. AB - Using a counterbalanced design, seven adult female rhesus monkeys were removed from their social group and housed in a novel environment both alone and with a companion chosen on the basis of quantitative affiliative behaviors. Blood samples (n = 2) were collected from all study animals before the exposure to the novel environment, then at 2, 24, and 96 h thereafter for cortisol and immunological analyses. During both conditions, subjects showed evidence of stress as indicated by elevated cortisol concentrations and decreases in absolute numbers of lymphocyte subsets. There was no significant interaction between condition (alone vs. companion) and time in cortisol percent change and further planned post hoc analyses showed no significant between-condition differences for any of the postseparation time points. Similarly, no significant interaction was found between conditions and time for the absolute number of CD4+CD8-T cells, CD8+CD4- T cells, or CD20+CD2- B cells. However, planned post hoc comparisons showed that subjects in the companion condition exhibited a significantly smaller percent change from baseline than in the alone condition at the 24 h and 96 h sample periods in absolute numbers of CD4+CD8- and CD8+CD4- T cells. Results showed that adult female rhesus monkeys exhibited a profound stress response when removed from their social group to a novel environment and that recovery time of T cell subsets was significantly enhanced by the presence of a preferred companion. PMID- 8190795 TI - Influence of the mother on development of aggressive behavior in male rats. AB - The present experiments investigated pre- and postnatal maternal effects on aggressive behavior in rats. Resident-intruder aggressive behavior of male rats in colonies (two males and two females) was studied in five experimental groups: 1 = WWY (n = 7) the two males of each colony were wild (biological father and mother were wild) fostered by a wild mother; 2 = WAY (n = 11) the two males were wild fostered by an albino Wistar mother; 3 = AAY (n = 11) the two males were albino (biological father and mother were Wistar) fostered by an albino mother; 4 = AWY (n = 12) the two males were albino fostered by a wild mother; and 5 = HWX+HAX (n = 9) one of the males was hybrid born and reared by a wild mother (the father was albino) and the other was also hybrid but born and reared by an albino mother (the father was wild). Each test lasted 10 min and the intruder was always a Wistar male. Aggression of wild rats was higher than the laboratory ones, independently of the mother (albino or wild) they were fostered by. However, hybrid males born and reared by a wild mother were more aggressive than those that were born and reared by an albino mother, in spite of the father being wild. In conclusion, crossfostering has little effect on territorial aggression, but prenatal maternal effects seem to play a major role on the ontogeny of aggressive behavior of male rats. PMID- 8190796 TI - Metabolic changes in lymphoid organs as induced by fatty acids-rich diets during ageing. AB - Previous reports of our laboratory have shown that w-6 PUFA-rich diets (UC) given to rats during 6 weeks causes important changes of the metabolism of the lymphoid organs. In this study, the effect of saturated fatty acids-rich diet (SC) and also the persistence of the changes caused by (UC) were investigated during ageing (14 months). The major changes previously reported for UC fed rats, during 6 weeks, fully persisted when this feeding condition was maintained for 14 months. Moreover, the SC group also showed modifications of the activities of key enzymes of glucose and glutamine metabolism of the lymphoid organs with ageing. Both groups fed fatty acids-rich diets markedly reduced the rate of lipogenesis in the liver, spleen, and thymus in contrast to slight changes reported for 6 weeks. These results suggest that fatty acids-rich diets, by causing important metabolic alterations, may pronounce the impairment of the immune function observed during ageing. PMID- 8190797 TI - Effects of intranasal ZnSO4 irrigation on olfactory and trigeminal cues. AB - Intranasal irrigation with ZnSO4 solutions is used for experimental induction of anosmia. It is, however, unknown whether the trigeminal nerve is affected by the treatment. One day after irrigation (concentrations investigated were between 0.05-1%) the ability of food finding, an olfactory cue, was decreased in a concentration-dependent manner. The trigeminal effect was investigated from a reflexively induced decrease in respiratory rate due to n-propanol exposure. No impairment occurred at 1% ZnSO4. Anosmia was also seen 2-3 h after an irrigation with solutions of 0.05-1% ZnSO4. At the same time, 0.2 and 1% solutions in themselves decreased the respiratory rate due to reflexes from the upper and lower respiratory tract. A conspicuous systemic effect can be ruled out as the Zn++ antidote, CaNa2EDTA, had no effect on the decrease. A direct activation of the trigeminal nerve due to a reaction with a thiol group may explain the effect from the upper airways. PMID- 8190798 TI - Effects of viscerosensory stimulation on hypothalamically elicited predatory behavior in cats. AB - Hypnogenic (HS) or arousing (AS) stimulations of the small intestine (INT), splanchnic (SPL), and vagal (VAG) nerves were used to modify the predatory behavior (PB) elicited by stimulating the lateral hypothalamus (LHS). HS induced EEG synchronization and sleep. AS aroused the cat from slow-wave sleep. LHS induced the cat to attack an anesthetized rat and bite its neck after an exploratory activity. The following parameters of PB were determined: biting latency (BL), the interval between the beginning of LHS and the touching the rat by the cat's muzzle; exploratory time (ET), which begins with an environmental search and culminates in orienting toward the rat; attack time (AT), in which the cat stalks and bites the rat. HS, delivered for 5, 10, 15 min to INT, SPL, and VAG prior to LHS, increased BL and ET and did not affect AT. AS, delivered for 10 s to INT or VAG prior to LHS, decreased BL by reducing ET. SPL AS shortened BL by decreasing both ET and AT. The viscerosensory effects on PB were decreased by increasing the intensity of LHS; a ferocious attack with BL less than 10 s was not influenced by either HS or AS. These results indicate that the viscerosensory influence can modify PB by inhibiting or facilitating the priming events of the attack. PMID- 8190799 TI - Pituitary grafts and behavior in mice. Effects of sex of donor and number of pituitary grafts on exploratory and learning abilities. AB - The effects of ectopic pituitary grafts, sex of pituitary donor, and number of isografts (one or two) were examined in intact phenotypically normal male mice of the Snell dwarf strain, using a battery of tests designed to assess exploration and learning-related behavioral processes. Results show that neither sex of pituitary donor nor number of grafts affected behavioral responses to pituitary grafts. Ectopic pituitary grafts increased the level of exploratory activities assessed in a novelty preference test and in the hole board test, facilitated the retention of a step-through type passive avoidance task--contrasting with results in rats--but did not affect spatial orientation in a spontaneous alternation and a water escape task. The results argue for a global effect of the graft, inducing increased emotional reactivity. PMID- 8190800 TI - Stimulus control of behavioral inhibition in the preweanling rat. AB - Previous studies demonstrate that 14-day-old rats reduce their emission of ultrasonic vocalizations and freeze when exposed to an unfamiliar adult male rat. This study sought to identify the stimulus characteristics of conspecific males that potentiate the display of behavioral inhibition. In Experiment 1, day 14 rats were isolated from the nest and exposed to either an unfamiliar prepubescent male rat or an unfamiliar adult male rat. Pups exposed to the unfamiliar adult male rat exhibited significantly elevated levels of freezing and reduced their emission of ultrasounds. In Experiment 2, pups were exposed to either a familiar or an unfamiliar adult male rat. Although several pups exposed to the familiar adult male rat exhibited freezing, pups tested with the unfamiliar adult rat showed a reliably higher duration of freezing and made fewer vocalizations. Results suggest that neither the unfamiliar factor nor cues associated with male adulthood are sufficient to account for the occurrence of behavioral inhibition when presented separately. However, the combination of unfamiliarity and adult male stimuli are highly potent stimulus features that elicit behavioral inhibition in preweanling rats. PMID- 8190801 TI - Gait analysis in the rat as a model for the study of peripheral vascular disease. AB - A number of problems are associated with investigation of the pathophysiology of peripheral vascular disease (PVD) in humans and unilateral ligation of the common iliac artery in the rat has been extensively used as an experimental model of PVD. However, techniques so far applied to monitor the effects of PVD on muscular function are invasive and difficult to relate to natural locomotion. The present study aimed to investigate gait during spontaneous, unforced locomotion in the animal model. No differences were observed between control and experimental rats in velocity or stride lengths. Although stride time was unchanged, its internal balance was disturbed with reduced stance, prolonged swing, for the ligated limb (LL) relative to the nonligated limb (NLL). Gait symmetry was also affected with NLL strike occurring earlier during LL stance. Analysis of footfall patterns showed a reduction of stance area and pressures exerted via LL relative to NLL. It is concluded that gait and footfall analysis could be useful for assessing limb function under natural exercise conditions. PMID- 8190802 TI - Meal patterns in response to the intracerebroventricular administration of interleukin-1 beta in rats. AB - Interleukin-1 beta (IL-1 beta) depresses feeding in rats when administered peripherally (in the microgram range) or centrally (in the nanogram range). In the present study, the effects of the intracerebroventricular (ICV, into the third ventricle) microinfusion of recombinant human IL-1 beta (rhIL-1 beta) on the microstructure of feeding in rats maintained ad lib were investigated with a computerized behavioral monitoring system. ICV microinfusion of rhIL-1 beta (0.5 to 4.0 ng/rat) decreased the short- (2 h) and long-term (nighttime) intake of pellets by reducing meal size and meal duration. Eating rate decreased, indicating a greater effect on meal size than on meal duration. Only the highest dose (4.0 ng/rat) decreased nighttime meal frequency and prolonged nighttime postprandial intermeal intervals. Water intake and locomotor activity also decreased. Water intake-to-food intake ratios in the 2.0 and 4.0 ng/rat rhIL-1 beta-treated groups increased, and this indicated a greater effect of rhIL-1 beta on food intake than on water intake. During the following daytime, meal parameters increased, suggesting compensation for the previous nighttime changes. However, these daytime compensatory responses were limited, and the total daily meal parameters were still decreased. The concomitant ICV microinfusion of rhIL-1 beta (1.0 ng) and recombinant human interleukin-1 receptor antagonist (rhIL-1ra, 500 ng) completely blocked the changes in the microstructure of behavior induced by rhIL-1 beta. This evidence suggests specificity of IL-1 beta inducing behavioral changes by direct action in the central nervous system. PMID- 8190803 TI - Melatonin replacement nullifies the effect of light-induced functional pinealectomy on nociceptive rhythm in the rat. AB - Rats maintained on a 12 h daily photoperiod (12:12 LD cycle), exhibited a diurnal variation in sensitivity to both heat-elicited and pressure-elicited pain, with low sensitivity at 2 h before the end of the scotophase and higher at 4 h after the onset of photophase. Functional pinealectomy induced by a single LL day effaced the baseline diurnal rhythm of sensitivity to pressure-elicited pain, and reversed that to heat-elicited pain. Oral administration of physiological doses of melatonin into functionally pinealectomized rats, nullified the effect of functional pinealectomy, restoring the normal baseline rhythms of both pressure elicited and heat-elicited nociceptive responses. The role of melatonin in modulating nociception is discussed in light of an indoleaminergic-opioid system. PMID- 8190804 TI - Construct validation of behavioral indices of isolation stress and inflammatory nociception in young domestic fowl. AB - Isolation from conspecifics can elicit a variety of behavioral responses in young domestic fowl that include increased vocalizations (VOC), ventral recumbency posturing (VRP), hypoalgesia, and hyperthermia. During tests of acute inflammatory nociception, chicks not only display several pain-related behaviors (i.e., footpecks and lifts), but also VOC and VRP. However, systematic evaluation of whether these behaviors reflect converging indices of stress and nociception remains to be conducted. In two separate experiments, 7-day-old chicks received intraplantar formalin (0.05%) or saline (0.05 ml) and were placed in sound attenuating chambers with or without two conspecifics for a 3 min observation period. The following measures were recorded: VOC, footlift frequency (LFT), and duration (DUR, Experiment 2 only), pecks (PKS), ventral recumbency latency (VRL), body temperature (BTMP), and body weight (WGT). Principal component analyses revealed the presence of two oblique and nonmonotonically related components, one consisting of pain-related measures (i.e., LFT, DUR, and PKS) and the other consisting of stress-related measures (VOC, VRL, and BTMP). A third component, consisting of BTMP and WGT ostensibly reflects maturational variability in thermoregulatory capability. These findings support the construct validity of these behavioral indices of isolation stress and inflammatory nociception and are consistent with the notion of stress effects on nociceptive processing. PMID- 8190805 TI - Effects of chronic stress on food intake in rats: influence of stressor intensity and duration of daily exposure. AB - The effect of exposure to chronic intermittent stressors of differing intensities [handling, restraint, and immobilization (IMO)] and daily duration (15, 60, and 240 min of IMO) on changes in food intake was studied in adult male rats. Whereas handling did not caused anorexia, restraint slightly reduced food intake and IMO drastically reduced it. The effects were very similar after the 7th and 27th day of exposure to the stressors. Fourteen days of chronic IMO (2 h daily) resulted in decreased food intake as measured on days 1, 10, and 14 of treatment, the inhibition being slightly greater after the first stress session. The circadian rhythm of food intake, expressed as a percent of the total food eaten in a 24 h period, was found to be almost unaffected by chronic IMO, although IMO rats appeared to satiate sooner than control rats. Exposure of rats to chronic IMO (7 days) for 15, 60, and 240 min daily reduced food intake to the same extent in all IMO groups. Taken together, these results suggest that: a) the magnitude of the changes in food intake after chronic exposure to stressors is closely related to their intensity, and b) a severe stressor such as IMO reduces food intake to a certain level that was independent on its daily duration. After repeated exposure to the same stressor, only a slight tendency to recover normal food intake was observed. PMID- 8190806 TI - Septo-hypothalamic organization of a stereotyped behavior controlled by vasopressin in golden hamsters. AB - In golden hamsters, microinjections of arginine vasopressin (AVP) within the anterior hypothalamus (AH) and lateral septum (LS) elicit the display of a stereotyped behavior: flank marking. As these areas are reciprocally connected, we tested whether AVP-sensitive sites constitute an organized network. Flank marking was recorded in animals with ibotenic acid lesions within the AH or LS after AVP injections within the LS or AH. While AVP injections in the AH and LS induced high flank-marking scores, certain lesions blocked the behavior. Lesions of the LS failed to affect flank marking induced by injections within the AH. In contrast, unilateral AH lesions blocked flank marking induced either by LS injections or AH injections in the contralateral side. These results suggest that the bilateral integrity of the AH is critical for the activation of flank-marking behavior by AVP. Together, these data suggest that the AH is an important relay of the neural network controlling flank-marking behavior. PMID- 8190807 TI - Olfactory cues mediate food selection by young chicks. AB - An illness-induced aversion paradigm was used to assess the possible influence of olfactory cues on food selection by young chicks. At 2-3 days posthatching, chicks were exposed briefly to food scented with a novel odor (orange) followed by an injection of LiCl or saline. LiCl-injected chicks subsequently displayed stronger avoidance of orange-scented food than did the controls. Chicks in a second experiment were preexposed to novel-scented food, then either injected with LiCl or not injected. The LiCl chicks, but not the controls, later avoided food associated with the preexposure odor (relative to food treated with an unfamiliar odorant). Two- to three-day-old chicks are capable of associating specific food odors with negative consequences and modify their feeding behavior as a function of such experience. PMID- 8190808 TI - Heart rate dynamics during human sleep. AB - To investigate the dynamics of heart rate in the course of sleep and to relate cardiac activity to sleep intensity, the electrocardiogram was recorded concomitantly with the polysomnogram in healthy young males. Heart rate was assessed across consecutive non-REM sleep (NREMS)-REM sleep (REMS) cycles as well as within individual episodes of NREMS and REMS. Within a sleep cycle, heart rate was lower in the NREMS episode than in the subsequent REMS episode. A global declining trend was present over successive NREMS episodes and over successive REMS episodes. A rapid increase of heart rate at the NREMS-REMS transitions was followed by a slow decline that started within the REMS episodes. Heart rate variability was higher in REMS than in NREMS and showed an increasing trend over successive REMS episodes but not over successive NREMS episodes. EEG slow-wave activity (spectral power density in the 0.75-4.5 Hz band), an intensity measure of NREMS, declined across NREMS episodes and was not correlated with heart rate. The global trends and ultradian variations of heart rate may represent sleep state-dependent modulations and circadian variations of the autonomic nervous system, which are not fully reflected in the sleep EEG. PMID- 8190809 TI - Circadian rhythms of blood pressure, heart rate, and locomotor activity in spontaneously hypertensive rats as measured with radio-telemetry. AB - Circadian rhythms of blood pressure, heart rate, and locomotor activity were measured with implanted radio-telemetry transmitters in conscious, unrestrained spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). During the light period (0600 to 1800 h) systolic, diastolic, and mean blood pressure, heart rate, and locomotor activity were lower than during the dark period (1800 to 0600 h). During the first and the last hour of the dark period, all parameters showed a relative peak when compared to values during the rest of the night. The pattern of circadian changes in blood pressure, heart rate, or behavior was essentially similar in SHR and WKY. Blood pressure values were always higher in SHR than in WKY, but there was no general strain difference in heart rate or locomotor activity values. The administration of hydralazine in the drinking water resulted in a significant decrease in blood pressure in SHR and WKY, and a suppression of the difference between light-phase values and dark-phase values. By contrast, heart rate showed an overall increase in both strains, whereas locomotor activity was largely unaffected. These data show the validity of telemetry as a means of measuring circadian rhythms of blood pressure, heart rate, and behavior in freely moving rats. Apart from their characteristic hypertension, SHR show few differences with WKY with respect to other parameters, such as circadian rhythmicity, baseline heart rate values, or behavior. Some of the previously published differences between SHR and WKY may have been influenced by the stress of the experimental procedures used. PMID- 8190810 TI - [Multi-functional dementia rating scale: reliability and clinical validity]. AB - A new rating method was designed to evaluate five symptoms of dementia; disorders of memory, cognition, language, visuospatial functions, and personality, which are defined as recent neuropsychological criteria for dementias by Cummings and Benson. Thirty-two items were made from the items of the Hasegawa dementia scale and neuropsychological tests. Scales for the five symptoms of dementia were then constituted of the items. In semi-structured interview, 113 demented patients and 16 normal elderly volunteers were rated. Interrater reliability of the five symptom scales were tested by ANOVA ICC and all the symptoms had a significant reliability. The scores of the five symptoms were correlated with each other and with the scores of the Hasegawa dementia scale. A Principal Component Analysis was applied to the scores of the five symptoms. The largest principal component had correlations with the scores of the Hasegawa dementia scale and the scores of the all five symptoms and was interpreted as a factor for severity of dementia. This component explains about 70% of total variance of the data. The other 30% of the variance were explained by four principal components which were interpreted as factors of the differences of the scores of the symptom scales. Relations between the scores of the symptoms and regional cerebral blood flow (rCBF) measured using SPECT were investigated in 25 moderately demented patients which met the criteria of probable Alzheimer's disease of NINCDS-ADRDA. rCBF was calculated as a ratio of 123I-IMP uptake of the areas to the mean uptake of right and left cerebellum. Significant correlations were found between the scores of memory symptom and the rCBF of the left temporal lobe (r = 0.59: p < 0.01) and between the scores of personality changes and the rCBF of the both frontal lobes (r = 0.58, 0.54: p < 0.01). Results suggest the possibility that the distribution of brain damage reflects symptoms in dementia and also supports the validity of analytic evaluation of dementia symptoms by this scale. PMID- 8190811 TI - [A study of pathogenesis and symptoms of Tourette's syndrome--mainly on the importance of "startle reflex" through Latah reaction]. AB - There is no established theory on pathogenesis of Tourette's syndrome, but recently, a theory of the British school of behaviorism; 'transient tics' and the more serious case, Tourette's syndrome which ensues on the fixation of the startle reflex, have received attention. So we determined, whether pathogenesis and symptoms of Tourette's syndrome could be systematically explained by "the startle reflex theory". Authors assumed that the startle reflex was composed of two divided actions, a series of muscular movements which started with eye blinks and terminated in the flexion of lower limbs (the primary startle reflex system), and more purposeful and complicated actions which occasionally arose from these movements (the secondary startle reflex system). On the basis of this supposition, we considered simple tics which are usually called "tics", those are the manifestation of astonishment by the primary startle reflex system, and complex tics; echo phenomena, coprolalia, complex movements, and so on, which are said to be pathognomonic of Tourette's syndrome, are the expression of amazement by the secondary startle reflex system. Furthermore, we formulated a hypothesis that in the latter case, the secondary startle reflex system contains the senses of orientation and defense, and the defense mechanism which is innately imprinted in common throughout human race, and covered through individual development, is released and fixed in the form of complex movements or echo phenomena in an emergency, such as astonishment. To discuss further, we determined Latah reaction minutely (especially in "Imu" of the Ainu race in Japan) in which intricate symptoms had been suggested as one of the senses of defense, were closely related to Tourette's syndrome. For more concrete study, we presented two severe cases of Tourette's syndrome. Considering the circumstances mentioned above, pathogenesis and symptoms of Tourette's syndrome could be explained by the startle reflex theory. Finally, we analyzed several psychiatrical syndromes which were provoked by astonishment, we concluded that it was necessary to emphasize Tourette's syndrome was only a part of those more comprehensive syndromes which could be called "startle syndromes". PMID- 8190812 TI - [Does "incompetency" exclude "patient as a subject"?]. PMID- 8190813 TI - [Assessment of social disability of patients suffering from chronic mental illness with the role play test]. AB - Among the chronic mentally ill patients, disabilities invade most parts of their social functioning, and influences their long term course profoundly. It is important clinical issue to improve disability. Social skills training is assumed to be effective method to improve disability, and it has been disseminated over Japan recently. The assessment system to evaluate disabilities objectively at the viewpoint of social skills must be required to verify effects of social skills training, and to develop further effective therapeutic method. A role play test is the assessment tool for social skills through role plays under specific social conditions. It was reported to be useful as the method of functional assessment before treatment, and as the tool to evaluate effects of treatment to improve disability. PURPOSE: We created the Role Play Test (RPT) which was adapted to Japanese cultural background, and we tried to verify feasibility, reliability, and validity of the RPT. SUBJECTS: Thirty out-patients attending in the Day Hospital attached to Tokyo University Hospital. Twenty-six were schizophrenia, and 4 were other diagnoses. METHOD: Subjects were assessed with the RPT, BPRS, SANS, four rating scales for social functioning, and self-efficacy rating scale. The RPT was designed to assess components of social skills--social perception, role play behavior, and self-efficacy. Role play behaviors were recorded with video tapes for analysis of interrater reliability. The RPT is consisted of 12 scenes to evaluate social skills which are required in daily life. Statistical analyses were done with SAS (Statistical Analysis System). RESULTS: (1) The RPT was presumed to be feasible clinically, because the RPT could be practiced easily and responsibilities of both subjects and testers were not so much. (2) Interrater reliabilities assessed with ANOVA-ICC on 12 items was sufficiently high except one item. (3) Construct validity was certified through factor analysis, and criterion-related validity was certified through correlation analysis with other rating scales of social functioning. (4) Individual profile of the RPT should be useful instrument for functional analysis before social skills training. We also discussed on some hypotheses on the causal relationship between positive and negative symptoms and social skills. The RPT could be used as a tool to research causes of disabilities, and to evaluate improvement of social functioning after psycho-social intervention including social skills training, because the RPT can assess social skills quantitatively according to the cognitive-behavioral model. PMID- 8190814 TI - [Psychopathological study of hypochondriaco-cenestopathic symptoms in schizophrenia]. AB - There is evidence that the psychiatric importance of hypochondriacal or cenestopathic symptoms in schizophrenia is prone to be neglected, in so far as these symptoms are expressed through the discourse of somatic medicine. Psychopathological studies of these symptoms are few as compared to studies of other schizophrenic symptoms such as delusion or verbal acoustic hallucination. However, it could be said that such study is indispensable in developing both an understanding of schizophrenics and therapeutic strategies for the treatment of them, in so far as hypochondriaco-cenestopathic symptoms directly indicate a pathology of body-consciousness in schizophrenia. Motivated by these practical as well as theoretical demands, the author presents first of all statistical characteristics of hypochondriaco-cenestopathic symptoms based on a longitudinal study of 183 schizophrenic patients, who were observed for at least 5 years. All the patients satisfied the DSM-III-R criteria for schizophrenia. Taking into consideration these statistical characteristics, as well as certain detailed representative cases, the author proposes a new psychopathological perspective of the hypochondriaco-cenestopathic symptoms in schizophrenia. The essential result of this statistical investigation is summarized as follows. 81 schizophrenic patients exhibited the hypochondriaco-cenestopathic symptoms, accounting for 44.3% of the sample. If we exclude the cases which presented physical experience of being influenced (physikalische Beeinflussungserlebnis), appearance frequency of hypochondriaco-cenestopathic symptoms accounted for 27.9% of the sample. Among the manifestations of these symptoms, uncharacteristic somatic complaint was the most frequent. Here, the most common was pain of body (especially headaches). The second most common was complaint of easy fatigability. Concerning the appearance pattern of the symptom, we found no significant difference between the acute and chronic types, nor between the early and tardive types, while the complex type was significantly more frequent in comparison with the simple type. Among the other symptoms that co-occurred with the hypochondriaco-cenestopathic symptom, the most common was acoustic hallucination, whose frequency was highly statistically significant when compared to the non hypochondriaco-cenestopathic group. Regarding the relationship of the hypochondriaco-cenestopathic symptom with the subtypes of schizophrenia, the proportion of the paranoid type was significantly high in the non hypochondriaco-cenestopathic group. PMID- 8190815 TI - [Psychosocial effects of the Holocaust on the second generation of Holocaust survivors]. AB - A modified version of the questionnaire used in research with survivors of the holocaust was used in research of their children. Twenty two persons were interviewed in order to answer the following questions: What national identity do the children of the holocaust survivors have, especially as they come from mixed marriages? What influence on their identity do family relationships have? PMID- 8190816 TI - [Clinical pharmacokinetics of tricyclic antidepressants Part II. Drug therapy monitoring]. AB - Large interindividual variation in steady-state TCA plasma concentrations, the presence of active metabolites, narrow therapeutic range and life-threatening results of TCA overdosage constitute indications for therapeutic drug monitoring. Conditions which must be fulfilled in order that serum concentration measurements may be taken into consideration in routine practice were discussed. The most important ones are: relationship between TCA concentration and antidepressant effect, the knowledge of therapeutic TCA range and availability of rapid and sensitive analytical method. Pharmacokinetic methods of TCA dosage individualization were also described. TCA serum concentration monitoring and dosage individualization of these drugs allows the clinician to optimize treatment of depression. PMID- 8190817 TI - [Psychotropic profile of essential antidepressants (amitriptyline, imipramine, desipramine, chlorimipramine): comparative study]. AB - Comparative studies of the therapeutic activity of amitriptyline, imipramine, desipramine and chlorimipramine were studied in a group of 185 patients with endogenous depression. After standard 28-day treatment, the best results were obtained while using amitriptyline (improvement rate 67%, the greatest reduction in the Hamilton Depression Scale scored on 28-day of the treatment). The profile and characteristics of antidepressive action of all the drugs taken into consideration are comparable (including slightly more expressed sedative and deliberative effects of amitriptyline). Desinhibitive influence of desipramine and imipramine was not proved. Neither was tachythymoleptic activity of desipramine found. The study does not support the relation between the antidepressive action profile of tricyclic antidepressants and their influence on reuptake of monoamines (norepinephrine and serotonine). PMID- 8190818 TI - [Drug resistance in endogenous depression Part II. Refractoriness to antidepressants in affective disorders]. AB - Among 67 patients admitted for the first time to the hospital drug resistance was evaluated in the further course of disease for at least 3 consecutive depressive phases. It was established that drug resistance occurs (usually as a single episode) in 28% of patients with endogenous depression and it concerns 10% of all depressive phases. The drug resistance is more frequent after the 45th year of life. The incidence of therapeutic failures is 3% during the first depressive phase and goes up in the consecutive phases. The occurrence of drug resistance in the past has no prognostic value for the next phase. There is a certain subgroup of patients, characterized by repetitive drug resistance during several phases. This phenomenon needs further evaluation. PMID- 8190819 TI - [Zinc concentration in blood serum and in red blood cells in patients suffering from delirium tremens]. AB - Zinc concentration in the blood serum and in red blood cells was examined among 40 patients who suffered from delirium tremens. A considerably lower level of zinc concentration in blood serum and red blood cells has been observed among the patients with delirium tremens, in comparison with a control group. PMID- 8190820 TI - [Assessment of liver pathology on the basis of biochemical and ultrasonographic findings in a group of alcohol dependent patients]. AB - The paper presents the assessment of liver pathology based on clinical examinations, biochemical findings and abdominal ultrasound examination with colour Doppler modalities in a group of 40 alcohol dependent patients. Special regard was paid to the liver, it is size, echogenecity, homogeneity and flow patterns in the portal vein. No significant correlations between the biochemical and USG parameters of liver pathology and the intensity of alcohol withdrawal and the level of the alcohol dependence syndrome were found. It can be concluded that the biochemical parameters as well as ultra sound diagnosis of alcoholic liver disease do not allow to make a final diagnosis of liver pathology. PMID- 8190821 TI - [Assessment of changes in physiological status of alcohol-dependent patients in the course of 10-day detoxication treatment]. AB - Heart rate, respiratory rate, postural muscle tone and tapping in 14 alcohol dependent patients (type II ac. Cloninger) during 10 days of detoxification were investigated. Despite subjective mood increased, no longer observed were tachycardia and clinical symptoms of alcohol withdrawal; increased muscle tonus and faster respiration rhythm were observed. The observed physiological changes in alcohol dependent patients after 10 days of abstinence suggest that continuation of pharmacotherapy and psychotherapy after detoxification in acute alcohol withdrawal is recommended. PMID- 8190822 TI - [Psychosocial effects of the Holocaust on Jewish survivors living in Poland]. AB - A group of 26 holocaust survivors was interviewed. The aim of the project was to find answers to the following questions: 1) What are the differences between Jewish survivors of the holocaust and Polish ex-prisoners of concentration camps imprisoned for political reasons; 2) What are the differences between survivors in Poland and survivors described in western literature. Generally the interviewed survivors had similar PTSD symptoms to concentration camp prisoners and survivors described in western literature. They did not differ in their suspiciousness and the long period of maintaining silence about the holocaust and experiences connected with it. They did not differ in setting up families quickly, in wanting home and children, in creating their own world to feel safe and supported by the family. They did not differ in an excessively fearful, often overprotective attitude to their own children. Higher educational level and keeping not only holocaust but their origin secret are differences we have found. Differences. The research was conducted within the "Judaica" programme of the Department of History and Jewish Culture in Poland, the Jagiellonian University, Krakow, under the direction of Prof. Jozef Gierowski. PMID- 8190823 TI - The organizing effects of early relationships. AB - The Developmental Psychobiology Research Group (DPRG), based at the University of Colorado Health Sciences Center, brings together researchers from a variety of disciplines and institutions with the goals of sharing information and stimulating further investigations into all aspects of development. Every other year a retreat is held over the course of several days, with a focus on a particular theme that is addressed by guest speakers and members alike. The following collection of papers comprises the presentations of two of the speakers at the 1990 DPRG retreat and three other papers, relevant to the theme, that were presented at the retreat. PMID- 8190824 TI - Infant sleep, nighttime relationships, and attachment. AB - Much research, since the beginning of this century, has elucidated the sophisticated competencies of the human infant. It is now known that shortly after birth, the newborn is neither passive nor poorly organized as a participant in interaction. The infant is predisposed to actively engage the social and physical world, and to process novel information in a regular and predictable way. The infant is born with a propensity to choose (prefer) certain stimuli over others and is dependent upon actively participating in both biological and social regulation to maintain homeostasis (Stern 1985). PMID- 8190825 TI - Emotional availability in mother-twin dyads: effects on the organization of relationships. AB - The term "emotional availability" has evolved primarily in therapeutic contexts where it refers to the sensitive engagement of the therapist in the patient's narrative of life experiences and openness to the patient's emotional expressions (Emde 1980). In the therapeutic situation, emotional availability refers to the quality of the therapist in supporting the growth or development of the patient. It is anticipated that the outcome of the therapeutic experience will include an enhanced capacity for reciprocal emotional availability with others. PMID- 8190826 TI - The development of attachment: from control system to working models. AB - After two decades of theoretical and descriptive work, we know a great deal about the developmental course of early attachment relationships. We know considerably less about the mechanisms underlying consistency and change. Indeed, the most pressing issue in attachment theory is to explain well-replicated correlations between early care and subsequent patterns of secure base behavior, and between secure base behavior in infancy and subsequent behavior with parents and siblings, social competence, self-esteem, and behavior problems. As a step in this direction, we examine Bowlby's developmental outline, with an eye toward providing greater detail and incorporating traditional learning mechanisms into Bowlby's attachment theory. PMID- 8190827 TI - Intrinsic and extrinsic factors affect infant responses to maternal separation. AB - Responses of individuals to the loss of a primary attachment object may be quite variable. In humans, it has been suggested that only about 25% of bereavements result in substantial psychological or medical morbidity (Hamburg et al. 1975). In nonhuman primates, which are used to model responses to separation and loss, a similar estimate of about 25% has also been obtained (McKinney 1985). In addition, there are wide-ranging species differences in vulnerability with regard to the nature and severity of the response to maternal separation and/or loss. All of these findings suggest that there are important processes, intrinsic and/or extrinsic to the individual, that contribute to the probability that a loss will produce a major behavioral or physiological response. We have been systematically examining some of the factors that may account for a portion of this variability in two species of macaques (bonnet monkeys Macaca radiata; and pigtail monkeys, M. nemestrina). PMID- 8190828 TI - Early asthma onset: the interaction between family stressors and adaptive parenting. AB - It has been repeatedly noted by clinicians that psychological stressors appear to be associated with the expression of asthma in individuals who have a genetic vulnerability for developing the disease. While retrospective evidence has supported this clinical observation (Levitan 1985; Teiramaa 1986), the association between emotional stressors and illness onset can only be convincingly demonstrated using a longitudinal design (Mrazek 1988; Steinhausen et al. 1983). In 1985 the W. T. Grant Asthma Risk Study was designed to identify which physiological and psychological risk factors for asthma were most highly associated with eventual expression of the disease. Young infants who were genetically at risk for asthma were evaluated and their development was prospectively monitored. The primary objective of the longitudinal study was to identify risk factors for illness expression. If this were possible, these risk factors could then be targeted for intervention efforts designed to delay the initial onset of asthmatic symptoms. The ultimate objective of an effective intervention would be that for some children, the illness could be prevented completely. PMID- 8190829 TI - Integration of neuropsychological and behavioral neurological assessment in psychiatry: a case example involving brain injury and polypharmacy. AB - We present a case example that highlights the need for careful neurologic and neuropsychological reevaluations of psychiatric patients who sustain head injuries, and also illustrates the concept that psychopharmacological interventions may impair cognitive performance, especially in a brain-damaged person. As in a previous paper (Weinstein et al. 1991), we emphasize the importance of a multidisciplinary diagnostic and treatment approach that carefully considers psychodynamic, cultural, and neurobiological data. In our experience, a neuropsychological approach is particularly helpful in cases: (1) where brain dysfunction is suspected but focal neurological signs are not identified, and (2) where frank symptoms of medication toxicity are absent but cognitive impairment is greater than expected. PMID- 8190830 TI - Psychoanalytic thinking and organizations. AB - Psychoanalysis, potentially, is a theory that can expand the connections among seemingly diverse areas of human experience. Starting out as a discipline that discovers hitherto hidden connections within the individual and elucidates powerful subterranean forces producing profound effects on the surface, it holds out the promise of analogously (or causally) demonstrating intricate and unseen connections in the larger units in which all individuals live--family, tribe, organization. Overall, in today's end-of-the-20th-century world, we see the possibilities of using thinking developed in one discipline and domain to help understand another. PMID- 8190831 TI - Special issue: Cytokines, crf, and the brain. In honor of Dr. Frank Berkenbosch. PMID- 8190832 TI - Cytokines and the brain corticosteroid receptor balance: relevance to pathophysiology of neuroendocrine-immune communication. AB - Interleukin-1 (IL-1) and interleukin-6 (IL-6), and their cognate receptors, are expressed in hippocampal neurons, which are targets for corticosteroid hormones. Corticosteroids bind to intracellular receptors, that is, mineralocorticoid (MRs) and glucocorticoid receptors (GRs). MRs respond to low concentrations of the steroid, while higher concentrations are needed for additional activation of GRs. MR occupation appears relevant in hippocampal neurons for stability of ongoing transmission, for basal activity and sensitivity of the stress response system, and for behavioural reactivity and response selection. Additional transient GR activation suppresses excitability, facilitates recovery from the stress response, and promotes information storage. Thus, the balance of MR- and GR mediated effects appears critical for the long-term control exerted by corticosteroids over specific aspects of neuronal activity, stress responsiveness, and behavioural adaptation. Administration of IL-1 produces a long-lasting increase in corticosterone. IL-1 also influences MR function in hippocampus and causes a shift in the MR/GR balance, which may underlie prolonged activation of the HPA axis during an immune response. PMID- 8190833 TI - Therapeutic effect of the D2-dopamine agonist bromocriptine on acute and relapsing experimental allergic encephalomyelitis. AB - We examined the effect of bromocriptine (BCR) treatment on the duration and severity of neurological symptoms of acute experimental allergic encephalomyelitis (EAE), an animal model for demyelinating diseases, particularly multiple sclerosis. To mimic the clinical situation, BCR treatment was started after the onset of clinical signs. Furthermore, the effect of BCR treatment on the course of a chronic relapsing form of EAE was studied. BCR was injected at daily intervals in a dose that resulted in sustained suppression of plasma concentrations of prolactin, a pituitary hormone that plays a role in immunoregulation. In acute EAE, BCR therapy reduced both severity and duration of the clinical signs. In chronic relapsing EAE, BCR treatment did not affect the severity and duration of the first attack, but reduced the duration of the subsequent, second attack. Thus, BCR treatment improves the clinical course in animals with ongoing disease. These findings may have implications for the search for new therapeutic approaches in multiple sclerosis. PMID- 8190834 TI - Pituitary-adrenal and interleukin-6 responses to recombinant interleukin-1 in neonatal rats. AB - The cytokine interleukin-1 (IL-1) is a potent activator of the hypothalamic pituitary-adrenal (HPA) axis. During postnatal development, the rat appears to be hyporesponsive to many stimuli which activate the HPA system in adulthood. Since hyporesponsiveness depends to a large extent on the stimulus, these experiments investigated the ontogeny of the HPA axis and interleukin-6 (IL-6) responses to IL-1 beta. Six-, 9-, and 18-day-old pups were injected with human recombinant IL 1 beta and plasma ACTH, corticosterone (CORT) and IL-6 levels were measured. IL-1 beta administration resulted in age-dependent endocrine and immune responses. The younger neonates secreted less ACTH and CORT and more IL-6. This was not due to a lowered capacity of the pituitary to synthesize and secrete ACTH since peptide levels following adrenalectomy did not reveal age differences. These data suggest that the diminished response to IL-1 beta is due to the immaturity of neural circuits which may be required to fully activate the HPA axis to immune signals. PMID- 8190835 TI - Induction of plasma interleukin-6 by circulating adrenaline in the rat. AB - Adrenaline, which is secreted from the adrenal medulla during stress, is considered to be involved in the control of inflammation and immune responses. Therefore, we studied the effects of adrenaline on the plasma levels of one of the major pro-inflammatory cytokines, interleukin-6 (IL-6). Here we describe that in rats, SC administration of adrenaline induces a dose-dependent increase in plasma IL-6 concentrations, reaching its maximum after 2 h. In addition, intravenous (IV) infusion of adrenaline in a dose resulting in circulating adrenaline concentrations similar to those observed during stress, enhanced heart rate and increased plasma IL-6 concentrations. The increase in plasma IL-6 in response to adrenaline given by subcutaneous (SC) route and by IV infusion could be blocked by the beta-adrenergic receptor antagonist l-propranolol but not by d propranolol. Based on these data we conclude that under physiological conditions circulating adrenaline may be involved in the control of IL-6 production, and thereby may modulate inflammatory responses. PMID- 8190836 TI - Mechanisms of activation of the pituitary-adrenal axis by tissue injury in the rat. AB - To characterize the mechanisms of the pituitary-adrenal (P-A) response to tissue injury, rats were injected intramuscularly (IM) with turpentine. This resulted in marked elevations in the plasma concentrations of ACTH and corticosterone within the first hour after injection, which were attenuated by either total deafferentation of the medial basal hypothalamus (MBH) or neonatal capsaicin pretreatment. The plasma concentrations of corticosterone remained elevated for 18 h in the turpentine-injected rats, despite a return of ACTH toward control values (by 2-4 h). Bioactive concentrations of interleukin-6 (IL-6) in plasma rose markedly after turpentine, and its concentrations were significantly correlated with plasma corticosterone concentrations 4-8 h after turpentine. Pretreatment with IL-1 receptor antagonist (IL-1ra) attenuated the release of IL 6 and had a marginal effect on the corticosterone response 6 h after turpentine. These results suggest that the early and late phase of the P-A response to tissue injury are mediated by different mechanisms. PMID- 8190837 TI - Corticotropin releasing hormone is involved in exercise-induced elevation in core temperature. AB - To determine the involvement of corticotropin releasing factor (CRF) in exercise induced elevation in core temperature of female rats, CRF antibody or vehicle was injected intracerebroventricularly (ICV) into rats that had free access to exercise wheels for 6 weeks. On the day of injection, there were no differences in body temperature or activity following these injections. However, exercising animals had a significantly attenuated daytime temperature when compared to vehicle control animals at one day postinjection with the CRF antibody. Although these animals have significantly lower body temperature than the animals that received vehicle, the injection of CRF antibody had no effect on locomotor activity. Therefore, this decrease in temperature is not due to a reduction in activity. These results suggest that CRF is involved in the exercise-induced elevation in daytime body temperature. Since this antibody also attenuates fevers caused by IL-1 beta (and presumably other cytokines), it is possible that the daytime elevation in body temperature of exercising rats is mediated by IL-1 beta or other cytokines. PMID- 8190838 TI - Peripheral macrophage depletion prevents down regulation of central interleukin-1 receptors in mice after endotoxin administration. AB - Interleukin-1 receptors (IL-1R) have been characterized in the brain and pituitary gland of mice. Previous studies have demonstrated that following lipopolysaccharide (LPS) injection, IL-1R density decreases in the dentate gyrus and in the choroid plexus. Receptors present in the anterior pituitary gland remain unchanged under the same experimental conditions. In this study, we investigated the role of peripheral macrophages in LPS-induced downregulation of IL-1 receptors. Mice were injected with liposomes encapsulated with dichloromethylene diphosphonate (Cl2MDP), which induced a profound depletion of peripheral macrophages. Immunocytochemistry was used to determine the efficiency of macrophage elimination. Depletion of macrophages did not affect the density of central and pituitary IL-1R in non-LPS-challenge mice. However, the liposome treatment prevented downregulation of IL-1R in the dentate gyrus observed following LPS administration. In addition, LPS induced a slight decrease in IL-1R density in the choroid plexus but not in the anterior pituitary gland of liposome treated mice. These results suggest that peripheral macrophages play an important role in the LPS-induced modulation of central IL-1R. PMID- 8190839 TI - Synergy between tumor necrosis factor alpha and interleukin-1 in the induction of sickness behavior in mice. AB - Like interleukin-1, recombinant human tumor necrosis factor alpha (TNF alpha) has been found to decrease social exploration and induce weight loss in mice in a dose and time-dependent manner. The present study was carried out to study the interaction between these two cytokines. Mice were injected IP with subthreshold doses of TNF alpha (2.5 micrograms/mouse) and IL-1 beta (50 ng/mouse). Social exploration was decreased 2 and 4 h after injection of TNF and IL-1, but body weight was not affected. Subthreshold doses of TNF alpha (90 ng/mouse) and IL-1 beta (100 pg/mouse) were also injected intracerebroventricularly (ICV). Social exploration was decreased 1.5 and 3 h after injections of the two cytokines and body weight was decreased for 6 h. To test the possibility of central induction of IL-1 by TNF alpha, mice pretreated with IL-1 receptor antagonist (IL-1ra, 1.8 micrograms/mouse, ICV) were injected with 90 ng TNF alpha. Pretreatment with IL 1ra antagonized the depressive effect of TNF alpha on behavior, but had no effect on weight loss induced by this cytokine. These results suggest that TNF alpha induced behavioral alterations are mediated by endogenously released IL-1, whereas metabolic changes are dependent on the release of other cytokines. PMID- 8190840 TI - Activation of the hypothalamus-pituitary-adrenal axis by bacterial endotoxins: routes and intermediate signals. AB - Peripheral administration of endotoxin induces brain-mediated responses, including activation of the hypothalamus-pituitary-adrenal (HPA) axis and changes in thermoregulation. This paper reviews the mechanisms by which endotoxin affects these responses. The effects on thermoregulation are complex and include macrophage-dependent hyperthermic and hypothermic responses. Low doses of endotoxin, given IP, activate peripheral macrophages to produce interleukin (IL) 1 beta, which enters the circulation and acts as a hormonal signal. IL-1 may pass fenestrated endothelium in the median eminence to stimulate corticotropin releasing hormone (CRH) secretion from the CRH nerve-terminals. In addition, IL-1 may activate brain endothelial cells to produce IL-1, IL-6, prostaglandins, etc., and secrete these substances into the brain. By paracrine actions, these substances may affect neurons (e.g., CRH neurons) or act on microglial cells, which show IL-1-induced IL-1 production and therefore amplify and prolong the intracerebral IL-1 signal. In contrast, high doses of endotoxin given i.v. may directly stimulate endothelial cells to produce IL-1, IL-6, and prostaglandin-E2 (PGE2) and thereby activate the HPA axis in a macrophage-independent manner. PMID- 8190841 TI - Affect and memory in schizophrenia: negative emotion words are forgotten less rapidly than other words by long-hospitalized schizophrenics. AB - The objective of this study was to investigate the effect of emotion on the rate of forgetting by long-hospitalized schizophrenics. Neutral, positive and negative emotion word lists were read by long-hospitalized schizophrenic and normal control subjects. Subjects were tested for recall immediately and after a delay of about 48 h. The results showed that long-hospitalized schizophrenics: (1) remembered less information; (2) forgot rapidly over time and (3) the negative emotion list was forgotten less rapidly by schizophrenics than the positive emotion list. These findings cannot be explained by differences in discriminating power of tasks, primacy and recency effects in recall, drug status, age, sex or intelligence. The conclusions drawn were that long-hospitalized schizophrenics are characterized by the rapid forgetting of verbal materials, and negative emotion materials are forgotten less rapidly by schizophrenics than other materials. Organic and psychological factors may interact in producing these effects in long-stay but not in short-stay patients. PMID- 8190842 TI - Chronic palinopsia in schizophrenia. AB - Palinopsia seems to be a very rare phenomenon in functional psychotic disorders. In this paper, we report on a patient with chronic schizophrenia who displayed chronic persisting palinopsia embedded in a plethora of rare mental phenomena. The possible theoretical relevance of this observation is discussed. PMID- 8190844 TI - Do social and demographic factors influence the nature and localisation of somatic complaints? AB - Demographic characteristics of specific somatic complaints were studied systematically in 60 consecutive patients whose main complaints were bodily symptoms without organic pathology, to determine if the social and demographic factors in any way influenced the nature or localisation of specific common somatic complaints. The Scale for Assessment of Somatic Symptoms was used to systematically acquire details of individual complaints. The commonest somatic complaints identified were weakness of body or mind (72%), headache (67%), fatiguability (37%) and burning sensations (35%). Subjects with less education reported weakness of body and mind, and multiple sites of pain more often, but lethargy and fatiguability less often than those with higher education. Rural subjects reported burning sensations and pain in their extremities more frequently. A sensation of 'gas' was more often reported by younger subjects, and pain in the extremities by male subjects. The factors which determine the choice of somatic complaints remain elusive and the exact reasons for these demographic relationships are unclear at present. PMID- 8190843 TI - Splitting phenomena from a viewpoint of experiencing time: spectrum from multiple personality and hysteria to borderline personality disorder. AB - Splitting is defined from a viewpoint of experiencing time as an 'episodic loss or sudden shift of experiencing time induced by two opposing representational groups'. According to this definition splitting phenomena are examined in four cases arranged on a spectrum from multiple personality and hysteria to borderline personality disorder (BPD). The degree of splitting was most prominent in BPD. In Contrast to the hypermnesia associated with hysteria, that of BPD had the potential to develop into paranoia. Splitting phenomena were considered to operate as a defense mechanism against the development to paranoia. In all four cases it could be seen that the overflow of 'parole', corresponding to the hypermnesia, could not be fruitfully conceptualized due to the splitting phenomena. Assuring new integration was indispensable to the therapy of the four presented cases. PMID- 8190845 TI - 'Meaningful' patterns in visual noise: effects of lateral stimulation and the observer's belief in ESP. AB - Visual noise subjectively contains more meaningful patterns (1) when tachistoscopically presented to the left visual field, and (2) for persons who believe in extrasensory perception (ESP). These results indicate a possible right hemisphere mediation of delusional perception and suggest some delusional component in the belief in ESP. PMID- 8190846 TI - Young adult chronic patients: empirical results on subgroups and age. AB - The discussion about young adult chronic patients (YACPs) started in the literature in the early eighties. However, the insufficient operationalization of the YACP concept provoked some criticism. The aim of the present study was to examine whether there were operational differences between YACPs and older chronic patients, as well as between hypothesized subgroups. The results show, as expected, that the differences between YACPs and older patients correlate with age. But only the 'high-energy, high-demand' subgroup differs not only from the other YACPs but also from the older chronic patients concerning psychopathology, social functioning and their interaction with the social environment. After 35 they grow out of their typical behavior which is strongly determined by traits of borderline and antisocial personality disorder. The stigmatizing YACP label should therefore be replaced by a more precise description such as 'young long term patients with borderline or antisocial personality traits'. PMID- 8190847 TI - Phenomenology of mania in eastern India. AB - One hundred consecutively hospitalized cases fulfilling DSM-III-R criteria for bipolar disorder, manic type, were studied by using the Hindi version of the Present State Examination. There was a preponderance of young male patients. Almost all cases showed expansive mood, subjective ideomotor pressure and grandiose delusions. Flight of ideas was rarely seen. Delusions of reference and persecution were very common and so were religious and sexual delusions. The findings are discussed in the light of cultural factors. PMID- 8190848 TI - On the delusional experience of controlling other persons in acute schizophrenics. AB - I present cases in which patients feel that they are able to control other persons, and consider the features of this delusional experience and note some points concerning its treatment. This delusional experience does not continue for a long period and is accompanied by a suicidal tendency, a pathological consciousness of the disappearance of the self, and some catatonic experiences. These features are not accidental, but result from the essentially solipsistic quality of this delusional experience. So, from the symptomatic viewpoint, this experience can be considered as belonging to catatonic ones in the acute phase of schizophrenia. From the therapeutic point of view, the occurrence of this experience should be carefully examined, bearing in mind its short duration. And when we encounter this experience, we should make provision against its suicidal tendency that often inevitably impels us to carry out electroconvulsive therapy. PMID- 8190849 TI - Delusions and hallucinations in schizophrenic patients. AB - The Scale for Assessment of Positive Symptoms was used to measure delusions and hallucinations in 115 DSM-III-R schizophrenics. Our factorial analysis of the hallucinations and delusions resulted in three factors with appropriate internal consistency and frequency: a Schneiderian delusional syndrome, an auditory hallucination syndrome, and a paranoid syndrome that tend to be present in schizophrenics with later onset. These results should be cautiously interpreted due to their cross-sectional nature and to the size of the sample which does not ensure the stability of the factors. PMID- 8190850 TI - Coexistence of the delusions of infestation and body smell in schizophrenia: a case report. AB - The coexistence of the delusions of infestation and of body smell is reported. In the analysis of a schizophrenic patient, the authors suppose a connection between object loss and the formation of secondary symptoms. Delusions of infestation and/or body smell can be an indication for a careful psychological analysis in schizophrenia. PMID- 8190851 TI - Schizophrenic autism. 1. Historical evolution and perspectives. AB - Cardinal importance has often been attached to the term 'autism' within the scope of schizophrenic symptomatology since its introduction by E. Bleuler in 1911. However, this term has been used purely intuitively in most cases, giving rise to a great deal of speculation about autism and its role within different psychiatric disorders, speculation which could not then be examined empirically for lack of intersubjective definition. This article reviews and examines the historical concept of autism, and finally makes and discusses proposals for future perspectives on autism. PMID- 8190852 TI - Schizophrenic autism. 2. Proposal for a nomothetic definition. AB - Since its introduction by E. Bleuler in 1911, the so-called 'basic symptom' autism has often been considered cardinally important within schizophrenic symptomatology. A lack of precise definition and hence of reliability, however, has eroded the former importance of this term, which cannot be found in modern diagnostic systems. Using a specific text-analytical method, we evaluated all accessible publications on schizophrenic autism, focusing on the descriptive empirical approach. The entire material was then summed up in five essential points, providing a possibly more reliable (nomothetic) explication of the complex term of autism. PMID- 8190853 TI - Educating primary care providers about HIV disease: multidisciplinary interactive mechanisms. AB - As HIV-related prophylactic and therapeutic research findings continue to evolve, the Health Resources and Services Administration (HRSA) of the Public Health Service has created multidisciplinary mechanisms to disseminate new treatment options and educate primary care providers at rural and urban sites throughout our nation's health care system. HRSA has implemented (a) the International State of-the-Art HIV Clinical Conference Call Series, (b) the national network of AIDS Education and Training Centers, (c) the nationwide HIV Telephone Consultation Service, and (d) the Clinical Issues Subcommittee of the HRSA AIDS Advisory Committee. These collaborative and comprehensive efforts at HIV information dissemination target physicians, nurses, physician assistants, dentists, clinical pharmacists, mental health care providers, case managers, and allied health professionals. The sites where they provide care include public health clinics; county, State and Federal correctional facilities; private practice offices; community and academic hospitals; military and Veterans Administration facilities; hemophilia centers; schools of medicine, nursing, and dentistry; departments of health; chronic care facilities; visiting nurse and home care agencies; health maintenance organizations; and Indian Health Service clinics and hospitals. PMID- 8190854 TI - Defining and measuring the costs of the HIV epidemic to business firms. AB - Most published estimates of the costs of the epidemic of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) have been developed from the societal perspective, attempting to measure the burden of the epidemic to society in this country. Although societal cost analysis is well developed, relatively little is known about many of the factors influencing the costs of the epidemic to business firms. The business community may bear a substantial portion of those costs in the form of health-related benefits provided to workers. Other effects of the epidemic in the workplace are related to fears and stigma associated with the illness. The author compares frameworks for analyzing the costs of the epidemic to the business community and to society. Societal costs include direct costs, the resources used in providing health care, and indirect costs, the resources lost to society as a result of the epidemic. Costs to business include illness-based employment costs, legal or administrative costs, prevention costs, perception-based employment costs, care giver costs, and nonmonetary costs. Not all societal costs are borne by business, and businesses may incur costs that are not traditionally measured from the societal perspective. PMID- 8190855 TI - Implications of directly observed therapy in tuberculosis control measures among IDUs. AB - Tuberculosis (TB) is a rapidly growing problem among injecting drug users (IDU), especially those infected with human immunodeficiency virus. The authors review IDUs' responses to current TB control strategies and discuss the implications of their findings for the proposed implementation of directly observed therapy (DOT), a method for ensuring that patients take prescribed medication. Field workers carried out 210 ethnographic interviews with 68 IDUs in a Brooklyn, NY, community during 1990-93. Case studies suggested that many IDUs are uninformed about TB and often misinformed about their personal TB status. Ethnographic interviews and observations indicated that the threat of TB-related involuntary detainment may lead IDUs to avoid TB diagnostic procedures, treatment for TB, or drug abuse treatment, and to avoid AIDS outreach workers and other health-related services. IDUs who tested positive for the purified protein derivative (PPD) of TB sometimes have left hospitals before definitive diagnoses were made, because of a perceived lack of respectful treatment, fear of detention, or lack of adequate methadone therapy to relieve the symptoms of withdrawal from drugs. Current TB diagnosis and treatment systems are, at best, inadequate. The threat of TB-related detention discourages some IDUs from seeking any type of health care. There is an urgent need to educate IDUs about TB and to educate and sensitize health care providers about the lifestyles of IDUs. DOT may help in servicing this difficult-to-serve population, particularly if techniques are incorporated that have been developed for other successful public health interventions for IDUs. PMID- 8190856 TI - Health care barriers and interventions for battered women. AB - Family violence is a major public health problem. Battered women present with multiple physical injuries in hospital emergency rooms, clinics, and personal physicians' offices. Yet, they are often not identified as battered and fail to receive appropriate treatment for the nonphysical effects of these events. Instead, only discrete physical injuries are identified. The authors explore the literature to identify barriers in recognizing and treating battered women. These barriers are viewed as a microcosm of the larger public health problem in which battered women fear identifying themselves and often are not recognized by public health professionals. Some barriers pertain to the victims themselves; others can be attributed to the attitudes of medical care providers in emergency rooms, clinics, and private physicians' offices. The many faceted needs of victims require a variety of interventions including medical models, criminal justice intervention systems, and social models for change. Some intervention strategies that are currently being employed in various programs in the United States are described. PMID- 8190857 TI - School-based programs to reduce sexual risk behaviors: a review of effectiveness. AB - This review was undertaken in recognition of the mounting public health and social problems associated with adolescent sexual behavior and the importance of basing school-affiliated programs designed to reduce sexual risk-taking behavior on sound research. The authors were commissioned by the Division of Adolescent and School Health within the Centers for Disease Control and Prevention, Public Health Service, to review carefully the research on these programs and to assess their impact on behavior. The authors identified 23 studies of school-based programs that were published in professional journals and measured program impact on behavior. They then summarized the results of those studies, identifying the distinguishing characteristics of effective programs, and citing important research questions to be addressed in the future. Not all sex and AIDS education programs had significant effects on adolescent sexual risk-taking behavior, but specific programs did delay the initiation of intercourse, reduce the frequency of intercourse, reduce the number of sexual partners, or increase the use of condoms or other contraceptives. These effective programs have the potential to reduce exposure to unintended pregnancy and sexually transmitted disease, including HIV infection. These programs should be replicated widely in U.S. schools. Additional research is needed to improve the effectiveness of programs and to clarify the most important characteristics of effective programs. PMID- 8190858 TI - State health agencies and the legislative policy process. AB - A new era of health care reform places increasing pressure on public health leaders and agencies to participate in the public policy arena. Public health professionals have long been comfortable in providing the scientific knowledge base required in policy development. What has been more recent in its evolution, however, is recognition that they must also play an active role in leading and shaping the debate over policy. A profile of effective State legislative policy "entrepreneurs" and their strategies has been developed to assist health agencies in developing such a leadership position. Based on the experiences of State legislative liaison officers, specific strategies for dealing with State legislatures have been identified and are organized into five key areas--agency organization, staff skills, communications, negotiation, and active ongoing involvement. A public health agency must be organized effectively to participate in the legislative policy process. Typically, effective agencies centralize responsibility for policy activities and promote broad and coordinated participation throughout the organization. Playing a key role in the agency's political interventions, the legislative liaison office should be staffed with persons possessing excellent interpersonal skills and a high degree of technical competence. Of central importance to effective legislative policy entrepreneurship is the ability to communicate the agency's position clearly. This includes setting forward a focused policy agenda, documenting policy issues in a meaningful manner, and reaching legislators with the proper information. Once a matter is on the legislative agenda, the agency must be prepared to negotiate and build broad support for the measure. Finally, public health agencies must be active policy players. To take advantage of new opportunities for action, the public health (policy) leader must monitor the political environment continually.By working to anticipate and formulate legislation,health officials can form meaningful relationships with legislators and the community, which are the cornerstones of political strength. PMID- 8190859 TI - Legislative Cardiovascular Health Check: a multidisciplinary health promotion experience for South Carolina lawmakers. AB - The South Carolina Department of Health and Environmental Control has conducted a Legislative Cardiovascular Health Check for the past 4 years. The primary purpose of the event, held in the lobby of the State Capitol Building, is to increase the awareness of State legislators about the leading causes of death in South Carolina and about community-based health promotion services that are available. The health check emphasizes the relationship between modifiable risk factors and the development of heart disease, cancer, and stroke. These legislative events are organized by State health department staff members, but they are conducted by local health department personnel from throughout South Carolina. This approach is intended to build the capacity of these local staff members to communicate more effectively with their legislators and to carry out similar events at the county or community level. The health check is staffed by a trained multidisciplinary team, including persons designated as legislative liaisons. The liaison people contact legislators prior to the event and provide them with health status data specific to their respective districts. The Legislative Cardiovascular Health Checks have been attended by members of the General Assembly and their staffs, members of the Governor's staff and the Lieutenant Governor's office, and other employees of the State Capitol. An average of 380 people have participated annually. Screening activities have included blood pressure and blood cholesterol checks, with risk factor counseling and educational materials provided to each screened participant. During the past year, activities were expanded to include a variety of interactive exhibits related to nutrition, exercise, and smoking. Feedback from participants has been positive. The Legislative Cardiovascular Health Check is encouraged and supported by the upper management of the State health department and is now established as an annual event of mutual benefit to legislators and to State and local health department staff members. PMID- 8190860 TI - Rehabilitation in the nursing home: how much, why, and with what results. AB - Although rehabilitation is considered an important component of long-term care, few studies have looked at the factors associated with the provision of rehabilitation in this setting. The authors examined one State's skilled nursing homes to gain information on their rehabilitation practices. Data for this study came from a mail survey and from the licensing applications filed with the State Division of Facility Services. Sixty-nine percent of the State's nursing homes responded to the survey. All reported that they provided specialized physical therapy, occupational therapy, or speech therapy, or all three, but the numbers of patients reported to be enrolled in such therapies on a daily basis varied from 0 to 64 percent of the facility's census. Factors positively associated with the provision of rehabilitation included the number of full-time registered nurses on the staff and the belief of the facility administrator that the purpose of rehabilitation is to restore function so that patients can be discharged. Facilities that employed their own therapists rather than contract for these services reported significantly more patients enrolled in daily therapies. And a significant positive correlation was observed between the provision of daily rehabilitation services and discharge of patients in those facilities that hired their own rehabilitation staff. These findings suggest that the provision of rehabilitation in nursing homes has different goals and outcomes and that there are facilities with identifiable characteristics that appear more successful in returning patients to their homes. PMID- 8190861 TI - Factors affecting the frequency of health enhancing behaviors by the elderly. AB - The authors examined the frequency of health-enhancing behaviors practiced by the elderly living in community settings, with emphasis on the impact of disease and disability on the frequency of those practices. Data were collected through personal interviews with a probability sample of 667 respondents in a 4-county region of northeastern New York. Almost all respondents said they engaged in at least one health-enhancing practice on a regular basis. The most commonly reported behaviors involved dietary practices. Results of the analysis support the importance of differentiating among health-enhancing behaviors that are undertaken as primary levels of prevention, in contrast to those undertaken as secondary or tertiary levels of prevention. PMID- 8190862 TI - HIV education for the deaf, a vulnerable minority. AB - Large numbers of deaf and hard-of-hearing people are in danger of becoming infected with the human immunodeficiency virus (HIV). The deaf are particularly vulnerable because of language barriers, their unique culture, and the paucity of community services, educational programs, and general information directed to this population. The particular barriers that the deaf must face in learning about HIV protection range from inadequate schooling about human sexuality to the scarcity of locally available education programs outside the cities with high rates of HIV infection. The programs for the deaf in Houston, Los Angeles, and New York City are described as well as the array of national efforts directed to this special population. PMID- 8190863 TI - Public knowledge of prevention of dental disease. AB - The authors present data describing the level and extent of the general public's knowledge of oral diseases and their prevention. They discuss data from the 1990 National Health Interview Survey's Health Promotion and Disease Prevention Supplement in the context of national oral health objectives. They focus on demographic and socioeconomic differences seen in the public's knowledge of the preventive purposes of fluorides and dental sealants for dental caries and of symptoms of gum disease. Reported low levels of knowledge regarding oral disease symptoms and their prevention show the continuing trend reported during the past decade. Racial and ethnic minorities and groups with low levels of formal education demonstrate the least knowledge of prevention of oral diseases. For example, 76 percent of those with more than 12 years of schooling know the preventive purpose of water fluoridation, compared with 61 percent of those with 12 years, and 36 percent of those with less than 12 years of school. Efforts to increase levels of knowledge about oral disease prevention are required to achieve national objectives for oral health. PMID- 8190865 TI - Characterizing nutrient intakes of children by sociodemographic factors. AB - Data from 1,392 children ages 1 to 10, who were participants in the U.S. Department of Agriculture 1987-88 Nationwide Food Consumption Survey, were examined to determine how their diets compared with current dietary recommendations and to identify those sociodemographic factors associated with the greatest risk for not meeting the recommendations. Vitamin A, vitamin E, vitamin C, calcium, iron, and zinc were the nutrients most often consumed below recommended levels. Percentage of calories from fat and saturated fat and mean sodium intakes were above recommended levels for the majority of the children. Of the total sample, 81 percent met guidelines for cholesterol intakes. Multiple correlation regression analysis was used to determine the effect of the following factors on the children's nutrient intakes: geographic region, degree of urbanization, race, household size and income, age, education, and employment status of the male and female head of household. Age and sex of the child were entered as control variables. Level of urbanization affected the most nutrient intake variables, followed by race. Living in a rural area and being black were significant predictors for higher intakes of total fat, saturated fat, cholesterol, and sodium. Mean annual household income had no significant effect on any of the diet quality measures. Many of the children in the sample, however, participated in Federal food and nutrition programs that provided additional resources for food. PMID- 8190864 TI - Relationship between socioeconomic status, health status, and lifestyle practices of American Indians: evidence from a Plains reservation population. AB - This paper presents information on the prevalence of a variety of health behaviors and health conditions on an American Indian reservation in the Plains region of the western United States. In addition, data from two non-Indian comparison groups were used to examine the extent to which differences in health status and health behaviors between Indians and non-Indians could be explained by differences in socioeconomic status. The American Indian data were from a survey conducted in 1988 during an evaluation of a local community-based health promotion program, part of the Kaiser Family Foundation's Community Health Promotion Grants Program. The comparison groups were 12 communities in California surveyed in evaluating the Community Health Promotion Grants Program and three Plains States participating in the Behavioral Risk Factor Surveillance Survey. The results show that the higher prevalences of risk-taking behavior among Indians and their poorer self-reported health status remained after adjustment for socioeconomic status. Also, among Indians, higher levels of income and education were not associated with improved self-reported health status and lower prevalence of tobacco use, as was the case with the comparison groups. The higher prevalences of risk-taking behaviors and ill health among American Indians residing on one reservation, even among those with higher socioeconomic status, suggests a need for the investigation of other social and environmental influences. PMID- 8190866 TI - The relationship between language spoken and smoking among Hispanic-Latino youth in New York City. AB - This study was designed to examine the relationship between language spoken and smoking (at least once a month) among New York City Hispanic-Latino adolescents, using a large sample of specific Hispanic-Latino subgroups (Puerto Rican, Dominican, Colombian, and Ecuadorian youth) and controlling for social and environmental factors. The sample included 3,129 Hispanic-Latino students in 47 New York City public and parochial schools. Of the total sample, 43 percent were Puerto Rican, 20 percent Dominican, 7 percent Colombian, and 7 percent Ecuadorian. The students completed questionnaires that were designed to assess social and environmental influences on their smoking and determine what languages they spoke (English and Spanish) with parents and friends. Self-reported smoking data were collected by means of the bogus pipeline to enhance the veracity of self-reports. In the logistic regression model, including background, social influence, and language use variables, 101 students were smokers. Logistic regression analysis indicated that being bicultural (speaking both English and Spanish) at home and with friends appeared to increase the odds of currently smoking. Separate logistic regression analyses for girls and boys revealed that being bicultural at home increased the odds of currently smoking for boys but not girls. Results are discussed in terms of their implications for prevention. PMID- 8190867 TI - Evaluation of oral rehydration therapy in Matiguas, Nicaragua. AB - Use of oral rehydration salts is an effective tool to decrease deaths due to diarrheal dehydration. Following concerted educational efforts to introduce oral rehydration therapy, Nicaragua reported a significant decrease in deaths of young children from diarrhea and dehydration over a 5-year period. Further decline in the mortality rate has not occurred, however, and factors that would affect usage and impact are poorly understood. A health survey was administered in 155 randomly selected homes in Matiguas, Nicaragua, in July 1990. Caretakers of children were asked about their knowledge, attitudes, and practices in treating diarrhea in children younger than age 5. They were also asked to demonstrate their knowledge of mixing World Health Organization oral rehydration salts packets. Ninety percent of the respondents said they used oral rehydration therapy. The major reason quoted for not using it was dislike of the taste. Of the three-quarters willing to mix the oral rehydration salts, 62 percent prepared the solution correctly and 38 percent incorrectly. Knowledge about diarrhea and the role of oral rehydration therapy was high in this population, and those with this knowledge were more likely to use it. Respondents who learned to mix the oral rehydration salts at the health center had more years of education and were more likely to mix the salts correctly. In this study, there is a positive association between contact with the health center and correct use of the rehydration salts. The relationship of this association with morbidity and mortality needs further research. PMID- 8190868 TI - Short course training in epidemiology and biostatistics for graduate and undergraduate public health professionals. AB - The University of South Florida has developed short courses of 2 to 3 days in epidemiology and biostatistics geared to public health workers. A key focus is providing skills which will assist local and State public health units to assess their status and measure progress with respect to achieving their explicitly stated health objectives for the year 2000. The courses were developed after the identification of the training needs in health departments and other public health settings. The training objectives were (a) to enhance the biostatistics skills of professionals involved in the analysis of health data; (b) to reinforce basic knowledge of epidemiologic methods and its practical applications in public health settings, including measures of disease frequency and association, epidemic outbreak investigations, and the identification and use of surveillance data; and (c) to demonstrate the application of the risk factor approach to select the interventions needed to reach health objectives for year 2000 and how to evaluate such interventions. A total of 43 students have taken this course series. Professional staff in health departments cannot always enroll in formal training in epidemiology and biostatistics because of time limitations or a lack of a bachelor's degree. However, the need exists. An alternative to such training could be the short course program described in this paper. PMID- 8190870 TI - Prevalence of prone sleeping position and selected infant care practices of North Dakota infants: a comparison of whites and Native Americans. AB - A cross-sectional prevalence study was done in four primary care clinics (two rural and two urban sites) and four Native American clinics serving members of the Chippewa, Sioux, Hidasta, Arikara, and Mandan tribes, all in North Dakota, to determine the prevalence of prone, supine, and side sleeping position in white and Native American infants. Questionnaires for 325 infants (259 whites and 66 Native Americans) between birth and 6 months of age were completed by the infants' mothers. They reported that 69 percent of the infants slept prone, 17 percent slept supine, and 14 percent slept on their side. Native American infants, who are at 3.2 times the risk of Sudden Infant Death Syndrome compared with other North Dakota infants, slept prone 46.9 percent of the time compared with 74.4 percent of white infants (chi 2 = 23.61; 1 df; P < .0001). No differences were observed in the prevalence of the side sleeping position. Eighteen percent of the infants slept in the position reported due to advice from a physician or nurse, 8 percent of the infants slept with more than two blankets, and 5 percent slept with a pillow. Native American infants in North Dakota did not have a higher prevalence of exposure to prone sleeping position. PMID- 8190869 TI - Money isn't everything: rural physicians identify other factors that facilitate providing prenatal care for low-income women. AB - The problem of physicians dropping the practice of obstetrics is becoming more serious each year in the United States. Those who remain in practice are increasingly reluctant to serve women who receive Medicaid assistance. Previous research has tended to focus on low reimbursement and liability as barriers that physicians perceive to providing prenatal care to low-income clients. In a 1992 survey in rural Idaho, however, physicians who have been serving these clients for at least 4 years rated other factors equally or more important in treating low-income women. These other factors, discussed in this paper, have to do with the administrative and psychosocial support coordinated by public health nurses for their internal clients, the physicians, as well as for their external clients, pregnant women. PMID- 8190871 TI - The Cadet Nurse Corps, l943-48. PMID- 8190872 TI - New guidelines issued for primary care of people with HIV. PMID- 8190874 TI - HIV risk 10 times higher for migrant farmworkers. PMID- 8190873 TI - NIH to study immune system supplement in HIV-infected women. PMID- 8190875 TI - Scientific misconduct and the blind eye. PMID- 8190876 TI - The edentulous mandible opposed by natural maxillary teeth: a report of six cases treated with implant-retained prostheses. AB - Dental restoration of the edentulous mandible opposing natural maxillary teeth is often associated with a number of problems, particularly in the occlusion, and an accelerated rate of alveolar bone resorption in the edentulous mandible resulting from occlusal loading. The advent of osseointegrated implants would seem to provide a new means of treating these cases. Accordingly, the cases of six patients for whom either fixed partial dentures or over-dentures supported by Branemark implants were provided, are reviewed. Three of the mandibles were normal and three had bone grafts. Results so far indicate that this is a viable alternative for treating such cases. PMID- 8190877 TI - A denture replication technique following partial maxillectomy: a case report. AB - A variety of problems faces the prosthodontist attempting reconstruction of maxillary defects. There are various treatment options for patients requiring a partial maxillectomy and an obturator prosthesis. Reduced adaptability makes it difficult for the patient to learn to use a new appliance, unless existing skills can be employed. It is therefore helpful to reproduce familiar features of a patient's existing obturator, especially if this has been used successfully over a transition period. PMID- 8190878 TI - The anatomy of local anesthesia. AB - The trigeminal nerve is the great sensory nerve of the facial portion of the head, and an intimate knowledge of this nerve and its surrounding structures is a prerequisite to the application of profound local anesthesia without complication. In this review article, the classic description of the relevant anatomy is described and is updated with recently published research into anatomic variations that have an impact on the induction of clinical local anesthesia. Causes of both failure and complications of traditional local anesthetic techniques are explained, and recommendations for avoiding these pitfalls are made. PMID- 8190880 TI - Distal movement of the maxillary molar using an active removable appliance and extraoral force: a case report. AB - This paper reports on the bilateral distal movement of maxillary molars in the treatment of a dental Class II malocclusion with an appliance system that combines an active removable appliance with fixed molar bands and a cervical headgear. This combination of forces provides distal molar bodily movement where the molars have erupted or migrated mesially with a resultant loss of arch perimeter. The appliance system presented is a conservative, reliable technique that can be used to increase the maxillary arch length in growing as well as nongrowing patients. PMID- 8190879 TI - Subgingival and interproximal plaque removal using a counter-rotational electric toothbrush and a manual toothbrush. AB - The purpose of this study was to compare the subgingival and interproximal plaque removal of a manual toothbrush to that of an oscillating counter-rotational electric toothbrush. Ninety teeth were divided into control, manual, and electric groups and test teeth received a total of 20 seconds of brushing. The teeth were then anesthetized, extracted, stained, dried, and examined with a computer assisted video analysis system. The control group had 13.88% plaque-free interproximal surfaces, compared to 30.57% for the manual group and 53.23% for the electric group. The mean subgingival plaque-free measurement was 0.05 mm for the control group, 0.64 mm for the manual group, and 1.36 mm for the electric group. The differences between the means were statistically significant for both measurements. PMID- 8190881 TI - The ratio of the densities of dentinal tubules on the cervical and axial walls in cavities. AB - When dentin is exposed, the pulp and the oral environment communicate through the dentinal tubules. The density of the dentinal tubules is an important determinant in dentinal permeability. The purpose of this study was to investigate, with an indirect method, whether tubular density is higher on the axial or on the cervical wall in cavities in restorative dentistry. The results obtained indicated that density of tubules on the cervical wall was usually higher than that on the axial wall. Clinically, the cervical wall of restorations therefore warrants the same meticulous protection routinely provided to the pulpal wall. PMID- 8190882 TI - Effect of gap dimension on composite resin cement wear. AB - For composite resin and ceramic inlays there is little information about the survival of the luting agent. The purpose of this in vitro study was to relate the wear rate of the composite resin luting agent to interfacial gap dimensions and filler particle size. By controlling the gap dimension between the inlay and cavity preparation through use of the cement and horizontal gap width. It was confirmed that this relationship was linear. In addition, the inclination of the regression line was assumed to indicate the extent of wear. Therefore, the wear resistance of cements could be determined by determining this inclination. The results of this study revealed that two hybrid cements exhibited lower wear resistance than did a microfilled cement. PMID- 8190883 TI - An in vitro evaluation of a copolymerizable type of microfilled composite resin. AB - Prepolymerizing microfilled composite resins have gained acceptance as restorative materials. However, when used as a posterior material, many of them undergo debonding of the organic filler. Such a condition has been attributed to the fact that the filler particles are held to the surface of the resin matrix primarily by mechanical means. Recently, a composite resin has been developed in which the prepolymerized organic particle is bonded chemically to the resin matrix through copolymerization. The material consists of trimethyol propane trimethacrylate, and the numerous double bonds on the surface provide a means for chemical bonding. A three-bodied wear-testing device was used in conjunction with a series of experimental trimethyol propane trimethacrylate-containing polymers, and it was shown that most of these systems offered greater resistance to wear and marginal deterioration than did conventional systems. PMID- 8190884 TI - Light-hardened glass-ionomer-resin cement restoration adjacent to a bonded orthodontic bracket: a case report. AB - Light-hardened glass-ionomer-resin restorative cement has all the advantages of glass-ionomer cements and the additional feature of rapid hardening by visible light application. The new restorative formulation can be used to restore a carious lesion adjacent to a bonded orthodontic bracket. PMID- 8190885 TI - Adhesion dentistry--its effect on treatment planning: a point of view. AB - Dental procedures are designed to take advantage of and are limited by available materials. As these improve and become more advanced, so must techniques. This article addresses the effects of adhesive dental materials on treatment planning. PMID- 8190886 TI - A look at dental esthetics. AB - The surge of interest in the use of tooth-colored restorative materials and systems in recent years has been attributed partly to rapid developments in dental materials science and also to patient demand and operator interest. When overall dental appearance is considered, several factors are of significance, including tooth color, shape, and position; restoration quality; and the general arrangement of the dentition, especially of the anterior teeth. Each factor may be considered individually, but all components together act in concert to produce the final esthetic effect. However, although the clinician must be mindful of the patient's desires for a favorable cosmetic result, materials and techniques must be carefully selected, and restorations should be sufficient to withstand the forces of occlusion and mastication and provide long-term function. PMID- 8190887 TI - No to male mammographers. PMID- 8190888 TI - Kallen projection reveals metacarpal head fractures. AB - Routine radiographic views may not be able to provide a complete diagnosis of metacarpal head fractures because the metacarpal heads are superimposed in the lateral position. This article describes a new radiographic position developed by the author that projects the metacarpal heads free of surrounding anatomy. The Kallen tangential oblique projection can demonstrate fractures that may not be visualized clearly on routine radiographic views. PMID- 8190890 TI - Program accreditation: its role and value. PMID- 8190889 TI - Reducing motion artifacts during hepatic DSA. AB - In hepatic digital subtraction angiography, artifacts caused by diaphragmatic motion can interfere with the correct diagnosis of hepatic lesions. This article describes the feasibility of using the exhalation holding method in reducing diaphragmatic motion artifacts in hepatic DSA. The authors compared respiratory holding methods in 30 patients who underwent hepatic DSA. They performed a blind comparison of images to assess diaphragmatic motion artifacts. Results showed the images obtained by the exhalation holding method were superior to those obtained by the inhalation holding method in 20 out of 30 series (66.7%). PMID- 8190891 TI - A crack in the professional armor. PMID- 8190892 TI - Densitometers and sensitometers in QC. PMID- 8190893 TI - Exploring hyperactivity's biological link. PMID- 8190895 TI - Cooperative learning is active learning. PMID- 8190894 TI - Slick flick. PMID- 8190896 TI - The overlooked safety concern. PMID- 8190898 TI - Double lives. PMID- 8190899 TI - Information on transmission of hepatitis C incomplete. PMID- 8190897 TI - Cerium as capturing agent in phosphatase and oxidase histochemistry. Theoretical background and applications. PMID- 8190900 TI - Burst your patients' bubbles by recommending dry brushing first. PMID- 8190901 TI - Periodontal debridement. PMID- 8190902 TI - Make patients our allies now and for the future. PMID- 8190903 TI - A model for follicle selection and the determination of ovulation rate in the ewe. AB - A model for folliculogenesis is proposed that is based as far as possible on a knowledge of physiological, rather than anatomical, changes taking place during follicle development. The model is therefore functional, rather than descriptive, and consists of five classes of follicles that have been defined by their dependency and sensitivity to gonadotrophins. These classes are: primordial, committed, gonadotrophin-responsive, gonadotrophin-dependent and ovulatory. The model is an attempt to encourage discussion and to promote the integration of morphological models of folliculogenesis with recent advances in the molecular endocrinology of the ovarian follicle. Two hypotheses for the mechanisms that determine ovulation rate are developed in light of the model. In the first, multiple ovulation results when the viability of gonadotropin-dependent follicles is enhanced. In the second, multiple ovulation is caused by increasing the number of gonadotrophin-responsive follicles available for further development; this results from the increasing rate of folliculogenesis and the throughput of follicles. The final section of this paper examines how these two hypothetical mechanisms, which are not mutually exclusive, appear to account for most of the known genetical and environmental effects on ovulation rate of sheep. In particular, the effects of nutrition, genotype, exogenous gonadotrophins, immunity to both oestrogens and androgens, and immunity to inhibin are discussed. PMID- 8190904 TI - The placenta as hypothalamus and pituitary: possible impact on maternal and fetal adrenal function. AB - The human placenta appears capable of providing trophic support for the maternal and fetal adrenal cortices. This effect could be mediated both directly, through placental secretion of ACTH1-39 and other peptides, and indirectly via placental CRH1-41 stimulation of pituitary ACTH1-39 secretion. Thus, the placenta is likely to influence the progressive changes that occur in the maternal HPA axis during pregnancy and to promote the developmental changes that occur in the fetal HPA axis. These effects are likely to be of particular importance near term, when the maternal and fetal HPA axes are maximally active and the fetus is dependent upon elevated glucocorticoid levels for maturation of organ systems. Finally, evidence from a variety of studies implicates placental CRH1-41 and ACTH1-39 in the cascade of events involving glucocorticoids and prostaglandins that culminates in parturition. PMID- 8190905 TI - Seasonal reproduction in flying foxes, reviewed in the context of other tropical mammals. AB - Megachiroptera inhabit the Old World tropics and most are seasonal breeders having defined times of testis growth, mating and parturition. In Pteropus scapulatus, the little red flying fox, the robust rhythm of testis cycles is resistant to modification by photoperiod. P. poliocephalus, the greyheaded flying fox, can be manipulated by photoperiod but responds slowly and incompletely. Most mammals live in the tropics, many in seasonally harsh climates, and many breed seasonally. However, few long-lived tropical mammals have been investigated for photoperiodic entrainment of annual reproductive cycles, and only animals from the edge of the tropics have responded. Thus, in long-lived tropical mammals, factors that regulate seasonal breeding have not yet been identified. Endogenous oscillators may generate circannual rhythms centrally. Downstream pathways (reproduction, metabolism, antlers, etc.) may derive their rhythm directly from the oscillator or may be modified by environmental cues. Plasticity of the circannual oscillator resolves confusion from previous contrasts between circannual rhythms and environmentally cued patterns. Plasticity may continue throughout life (species responsive to zeitgebers), but the oscillator may be 'set' in utero in some tropical species. Feedback effects from temperature, nutrition, hormones, etc. can be readily tested in this model of an oscillator generating an endogenous circannual rhythm. PMID- 8190906 TI - Transforming growth factor-alpha: identification in bovine corpus luteum by immunohistochemistry and northern blot analysis. AB - Transforming growth factor-alpha (TGF-alpha), a product of the thecal cells, has potent mitogenic and steroidogenic influences on cells within the ovarian follicle. Whether TGF-alpha continues to be produced in those follicles that go on to ovulate and form a corpus luteum is currently under investigation. In the present study, TGF-alpha was localized in the bovine corpus luteum by means of immunoperoxidase staining using a monoclonal antibody for TGF-alpha that does not cross-react with epidermal growth factor. In corpora lutea from the mid-luteal phase of the cycle TGF-alpha staining was found predominantly in the large luteal cells. Northern blot analysis using a human TGF-alpha cDNA probe hybridized to the 4.5-4.8 kb TGF-alpha transcript in RNA from the corpus luteum. These studies provide new evidence that TGF-alpha, a potent paracrine regulator within the ovarian follicle, continues to be expressed in the corpus luteum. PMID- 8190907 TI - Determination of porcine endometrial phospholipase A2 activity and detection of immunoreactive cyclooxygenase during the oestrous cycle and early pregnancy. AB - Experiments examined the characteristics and activity of phospholipase A2 (PLA2) and examined the presence of immunoreactive cyclooxygenase in endometrium of pigs during the oestrous cycle and early pregnancy. Endometrial PLA2 was calcium independent and activity of the enzyme was greatest at a pH of 8.0. Activity of PLA2 on Days 10, 12, 14 and 16 of the oestrous cycle did not differ (P > 0.1) from activity on those days during pregnancy. During oestrus and early metoestrus (Days 0-3), cyclooxygenase was present in both glandular and surface epithelium. After Day 10 of the oestrous cycle or pregnancy, staining for cyclooxygenase was less intense in the lower and middle uterine glands. However, the upper glandular epithelium near the surface epithelium stained intensely. By Day 15 of the oestrous cycle or pregnancy, intense staining for cyclooxygenase appeared restricted to the upper uterine glands. These results indicate changes in localization of immunoreactive cyclooxygenase throughout the oestrous cycle and suggest that these are not related to altered secretion of prostaglandins (PGs) during early pregnancy. The stimulatory effects of porcine conceptus products on secretion of PGs during early pregnancy are apparently not associated with increased activity of endometrial PLA2. PMID- 8190908 TI - Effect of culture from the zygote stage on the metabolism of glucose and glutamine by 2-cell embryos and blastocysts recovered from outbred or F1 hybrid female mice. AB - The oxidation and incorporation of glucose and glutamine by embryos derived from cultured zygotes was compared with the utilization of these substrates by embryos recovered directly from the reproductive tract of pregnant females. The oxidation of glutamine was greater at the blastocyst stage than at the 2-cell stage. Embryos derived from outbred females (Qs) were less active in the oxidation of glutamine than those from hybrid (B10D2F1) females and development in culture was detrimental to this oxidation, especially in blastocysts from the outbred stock. The oxidation of glutamine was stimulated by the presence of glucose at the 2 cell stage but reduced by its presence at the blastocyst stage. Maternal genotype had no effect on the oxidation of glucose at either the 2-cell or blastocyst stage, and only at the blastocyst stage was there evidence of a detrimental effect of culture. The oxidation of glucose was stimulated by the presence of glutamine at the 2-cell stage but depressed by its addition at the blastocyst stage. Incorporation of glutamine increased with development, but this was reduced at the blastocyst stage by development in culture, especially if the blastocysts were derived from outbred females. Incorporation of glucose also increased with development. At the 2-cell stage, culture reduced incorporation of this substrate, especially into the acid-soluble fraction of embryos from outbred females. In blastocysts, incorporation of glucose into the acid-insoluble fraction was depressed by culture and in embryos from outbred females. In contrast to glucose oxidation, incorporation of glucose into the acid-soluble fraction was reduced by the addition of glutamine at the 2-cell stage but increased by its addition at the blastocyst stage. PMID- 8190909 TI - Gestation periods in the Pere David's deer (Elaphurus davidianus): evidence for embryonic diapause or delayed development. AB - It has been suggested that the gestation length of the Pere David's deer is around 280 days, which is significantly longer than any other deer species except the roe deer (approximately 300 days) which exhibits embryonic diapause. The present study was designed to determine whether embryonic diapause exists in the Pere David's deer by accurately monitoring gestation length. There was no difference in gestation length (283-284 days) between animals mated early and later in the breeding season. Hence, although Pere David's deer exhibit a longer gestation period than that predicted from maternal body weight, there is no evidence for seasonal control of implantation. Actual birth weight is as predicted from an interspecific comparison of ungulates. The data imply either that there is an obligate period of embryonic diapause, irrespective of season, or that postimplantation fetal growth rate is slow compared with that in other deer species. PMID- 8190910 TI - Changes in androgen concentrations during puberty and their relation to behaviour in male Saccostomus campestris (Gray 1844), an African rodent. AB - Sexual development in male Saccostomus campestris, the pouched mouse, was studied in terms of morphological development and changes in concentrations of plasma testosterone and androstenedione. The interaction of adult females and males following the introduction of a male was observed at all stages of the oestrous cycle. The histology of the reproductive organs is similar to that of other rodents. Measurements of the diameter of the seminiferous tubules and the width of the seminiferous epithelium suggest asymptotic growth but, although the diameter had not reached the asymptote at 70 days of age the epithelial width was close to the calculated asymptote at 55 days of age. Intraindividual variation was no greater than variation between individuals of the same age from 55-70 days. Spermatids were not seen in any animals younger than 45 days, but all animals over 55 days of age had spermatozoa in the epididymis. By 70 days of age, fertile matings were observed. At this stage, the seminiferous tubule diameter was still increasing slowly but plasma concentrations of testosterone and androstenedione had reached adult levels; at no time was the concentration of testosterone greater than androstenedione. The males were never aggressive towards females; however, they were severely attacked by females at all stages of the oestrous cycle except pro-oestrus. Only rarely did males show aggression to other males. PMID- 8190911 TI - Enhancement by streptozotocin-induced diabetes of pancreatic prolyl endopeptidase activity in neonatal rats. AB - The effect of streptozotocin (STZ)-induced diabetes on the concentrations of deamidated TRH (TRH-OH), a metabolite of thyrotropin-releasing hormone (TRH) and prolyl endopeptidase (PE) activity were studied in the pancreas of neonatal rats to determine the contribution of beta-cells to PE activity and TRH-OH levels that we have previously found in this tissue. STZ treatment caused a significant reduction of immunoreactive TRH-OH levels on day-3 and -5 compared to untreated control rats. Reverse-phase high performance liquid chromatography of pooled extracts of 3-day-old normal rat pancreas revealed that about 50% of immunoreactive TRH-OH was found in the fractions representing authentic TRH-OH, whereas the remaining 50% eluted earlier. In STZ treated rats, all of the TRH-OH immunoreactive was associated with this early peak, no authentic TRH-OH could be detected. The specific activity of PE, on the other hand, rose 2.5-fold in diabetic 3-day-old pups (4.06 +/- 0.13 compared with 1.59 +/- 0.83 nmol/min/mg protein, P < 0.01, in controls). This increase declined with age (1.6- and 1.3 fold in 5 day- and 7-day-old pups, respectively). STZ treatment did not change pancreatic PE levels in 20-day-old rats control. Normalization of STZ induced hyperglycemia by sodium metavanadate treatment or by replacement of exogenous insulin did not restore pancreatic PE activity. The enhancement of PE activity following STZ treatment was specific for pancreas tissue. Furthermore, beta cytoxin drugs other than STZ that cause permanent diabetes such as alloxan enhanced PE activity to the same extend. Kinetic studies for PE activity show that Vmax is 3-fold higher in 3-day-old STZ-treated than in rat controls. In contrast, values for Km were comparable in rats of both groups (25 to 34 microM). We then tested whether the decrease of Vmax might have been caused by the presence of an PE inhibiting factor in these preparations. Gel-filtration experiments of pancreatic extracts revealed that the total apparent activity of eluted PE in 3-day-old control rats was 2-fold higher than in the original extract. In contrast, the recovery of eluted PE activity was not increased in the case of STZ-treated 3-day-old and untreated 20-day-old rats. These findings demonstrate that TRH-OH is identified in beta-cells and that an inhibiting factor(s) present in beta-cells appear(s) to be responsible for the unexpected enhancement of PE activity observed in STZ-treated neonatal rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8190912 TI - Insulin-like growth factor I in human gastrointestinal exocrine secretions. AB - Insulin-like growth factor I (IGF-I) is the mediator of growth hormone dependent growth. The peptide has been identified by radioimmunoassay in a number of human exocrine secretions of the gastrointestinal tract including (nM): saliva 0.9, gastric juice 3.5, jejunal chyme 24.6, pancreatic juice 3.6, and bile 0.9. The identification of IGF-I in pancreatic juice was confirmed by HPLC. The intravenous injection of 1 unit/kg secretin increased pancreatic juice IGF-I content from a basal level of roughly 4 nM to nearly 20 nM. Conversely, the IGF-I content of bile was unaffected by secretin. Radioligand blot analysis of samples of gastric juice, jejunal chyme and pancreatic juice demonstrated that these fluids contained no IGF binding proteins. Thus, unlike IGF-I in serum, IGF-I secreted into the gastrointestinal lumen is not bound to insulin-like growth factor I binding proteins. Since the growth factor is not protein bound, its concentration in the gut lumen may be high enough to exert biological activity. PMID- 8190913 TI - Studies on the structure-activity of motilin in vivo. Effect of motilin synthetic analogues in conscious dog. AB - Synthetic analogues of motilin were tested for their capacity to stimulate the intestinal motor activity of the conscious dog. Physiological doses (75 pmol/kg) of motilin 1-22 and of motilin fragments 1-21, 1-20 and 1-19 induced premature periods of phase III activity in all tested animals. Motilin fragments 1-15, 1 12, 1-11 and 1-10 failed to influence the intestinal myoelectrical activity even when given at doses 10-times superior (750 pmol/kg). Motilin-like immunoreactivity was measured in plasma during the analogues infusion. During the infusion of the bioactive analogues (1-22, 1-21, 1-20, 1-19), plasma motilin increased by 174 +/- 25 fmol/ml while a small rise (22 +/- 7.6 fmol) was noted with the inactive fragments (P < 0.001). Our data are in agreement with the in vitro findings that the N-terminal portion of the motilin molecule is responsible for its biological activity and suggests that the middle portion of the molecule is important to prevent degradation and maintain biological activity in vivo. PMID- 8190914 TI - In vivo effect of chronic administration of vasoactive intestinal peptide on gut associated lymphoid tissues in rats. AB - The in vivo effects of chronic administration of vasoactive intestinal peptides (VIP) on the lymphoid cell traffic and the population and function of cells in intestinal lymph and gut-associated lymphoid tissues were examined in rats. VIP was continuously infused from the superior mesenteric artery in rats at a dose of 10 ng/min/kg body weight for 96 h. Lymphocyte transport through intestinal lymph was significantly reduced by VIP without any changes in lymph flow. When lymphocyte subpopulation was examined in intestinal lymph, T cell subsets were decreased with a dominant reduction in the population of helper T cells. T cell subsets were also decreased in mesenteric lymph nodes, but in this case suppressor/cytotoxic T cell subsets were mainly reduced. Despite of the decrease in lymphocyte transport through intestinal lymph and changes of lymphocyte subpopulation, proliferative response of lymphocytes from intestinal lymph and mesenteric lymph nodes to phytohemagglutinin did not show any significant alteration after administration of VIP. By histochemical study on the lamina propria of the small intestine, the population of pan T cells, especially helper T cells, was demonstrated to be significantly decreased after VIP treatment. There was also a marked decrease in the number of immunoglobulin (Ig) A containing cells in the lamina propria of the small intestine in VIP-treated rats, while no significant changes were seen in the number of IgG and IgM containing cells. Our present results showed the possibility that a long-term alteration of serum VIP levels could affect the dynamics of immune effector cells and IgA production in gut-associated lymphoid tissues. PMID- 8190915 TI - Modulation of tachyphylaxis to angiotensin II in rabbit isolated aorta by the angiotensin AT1 receptor antagonist, losartan. AB - In rabbit aortic strip preparations, angiotensin II (AII) concentration contractile response curves (0.3-100 nM) were highly reproducible. However, tachyphylaxis to the contractile response elicited by AII could be induced by repeated exposure to a supramaximal concentration (10 microM) of the peptide. In contrast, a correspondingly supramaximal concentration of the alpha 1 adrenoceptor agonist, phenylephrine (1 mM), did not cause the tissue to become tachyphylactic to phenylephrine. Furthermore, phenylephrine responses were unaffected in tissues previously made tachyphylactic to AII. When the non peptide, competitive angiotensin AT1 receptor antagonist, losartan (300 nM), was administered before each supramaximal AII challenge, tachyphylaxis did not subsequently occur. Additionally, in tissues made tachyphylactic to AII, subsequent incubation with losartan (300 nM) reversed the AII tachyphylaxis. Thus, losartan may prevent the loss of contractility by preventing AII from interacting with its receptor in a manner which induces tachyphylaxis. However, since losartan can also completely reverse the loss of contractility, it appears capable of restoring the AT1 receptor to a state which allows subsequently administered AII to fully activate the contractile pathway. PMID- 8190916 TI - Purification of a neuropeptide Y-related peptide from the brain of the sea lamprey and its effect on steroidogenesis. AB - A peptide with neuropeptide Y-like immunoreactivity was identified by radioimmunoassay in an extract of the brain of the sea lamprey, Petromyzon marinus using an antiserum raised against the conserved COOH-terminal region of mammalian neuropeptide Y. Purification of the peptide and determination of its primary structure showed that it was identical to peptide methionine-tyrosine (PMY), previously isolated from the intestine of the same species. Intraperitoneal injection of synthetic PMY (0.15 micrograms/g) into female lampreys undergoing final maturation before spawning produced a significant (P < 0.05) decrease in plasma concentrations of estradiol compared with control lampreys injected with vehicle only. These data suggest the hypothesis that the observed decrease in the concentration of PMY-containing cells in the intestines of lampreys during upstream migration may correlate with the increase in circulating estradiol concentrations and final maturational processes. PMID- 8190917 TI - Vasoactive intestinal peptide (VIP) mRNA expression in rat T and B lymphocytes. AB - Different evidence suggests that VIP has immunoregulatory functions and may be secreted by different cells involved in inflammatory and immune responses. In the present study, we demonstrate by reverse transcription (RT) and polymerase chain reaction (PCR) VIP gene expression in rat thymocytes and T and B cells derived from spleen and lymph nodes. We have obtained a specific VIP cDNA product of 458 bp identical in size to that obtained from cerebral cortex. These results have been confirmed by Southern blot analysis. VIP message has also been detected in the T-T hybridoma YH-1633 and in a non-immune cell line, the pheochromocytoma PC 12. VIP gene expression in central and peripheral lymphoid organs suggests that VIP may be a T and B cell-derived cytokine involved in T-cell differentiation and in cell immune responses. PMID- 8190918 TI - [The evolutionary effects of therapy on the skeletal lesions in beta thalassemia]. AB - Up to the mid-1960s, beta-thalassemia was treated with blood transfusions as frequent as needed to keep symptoms under control and to prevent transfusional hemosiderosis. In the following years, high transfusion regimens and iron chelation therapy with desferrioxamine were used. Because of these different treatment modalities, skeletal findings in thalassemia have markedly changed. In the past, thalassemic patients treated with a low transfusion regimen and without chelation therapy developed osteopenia--with widened medullary spaces, cortical thinning and trabecular atrophy--secondary to chronic expansion of red marrow, due to increased erythropoietin response to chronic anemic hypoxia. Typical radiographic patterns in the skull included widened diploic space, atrophic especially outer--tables and, in some patients, the "hair-on-end" pattern. As for the face, obliteration of the paranasal sinuses and the typical "rodent facies" were observed. In the ribs, bulbous expansion of the posterior and anterior segments and the "rib within a rib" patterns were observed. As for the spine, coarse trabecular arrangement was seen. The "cobweb" pattern was seen in the pelvis and finally the lack of the normal concave outline was observed in the long bones. In the patients treated with high transfusion regimens and iron chelation therapy over the last 30 years, both skull anomalies and disfigurement are less frequent. The skull is almost normal, with the exception of osteopenia and thickened diploic space in the frontal bone only; the paranasal sinuses are usually not obliterated. The hands and rib are normal, just like long bones, pelvis, scapulae and vertebral bodies. Nevertheless, in some adequately treated patients new skeletal features have been recently observed in the long bones, which are similar to those occurring in rickets and/or scurvy, and in the vertebral bodies, resembling platyspondylia. These abnormal features might be caused by several factors--i.e., marrow expansion, transfusion regimens, direct/indirect effects of desferrioxamine, iron load, endocrine abnormalities, deficiency of some minerals and finally dysvitaminoses. Nevertheless, osteopenia remains the main negative factor of thalassemia. PMID- 8190919 TI - [Anomalies of the masticatory apparatus in beta-thalassemia. The present status after transfusion and iron-chelating therapy]. AB - Fifty-four homozygous beta-thalassemic patients (26 men and 28 women) aged 7 to 24 years, who had been treated with high transfusion regimen (Hb levels = 9-10 g/dl) and chelation therapy (desferrioxamine, 35-50 mg/kg), underwent clinical and radiographic investigations. This study was aimed at assessing the clinical and radiographic changes in the stomatognathic system (teeth, mandible and maxilla, occlusion relationship and dental bases). All patients underwent orthopantomography and teleradiography of the skull, in the lateral view. Twenty thalassemic patients (13 men and 7 women) of the same age but treated with low transfusion regimes (Hb levels = 5-6 g/dl) were examined as a control group. Our results indicate that: 1) in the control group, osteopenia is the specific lesion of anemia, in both the alveolar process and the mandible, following marrow expansion. Consequently, diastema of incisors and several types of malocclusion follow--i.e., overjet, anterior open-bite and crossbite, nearly all of them associated with II dental and skeletal patterns of Angle's classification. 2) In adequately transfused patients, no lesions are observed in 55% of cases, in both the teeth and the facial skeleton. This means that current treatment methods can prevent bone abnormalities, especially if transfusions begin at birth. Nevertheless, osteopenia of the mandible (31.4%) and dental and/or skeletal malocclusions (40.7%) remain in many cases, because of persistent marrow expansion, which usually follows incorrect treatment. 3) General dental diseases- e.g., caries, paradentosis, gingivitis, etc.--affect both populations with the same incidence. PMID- 8190920 TI - [Lumbar spondylolysis and sports. The radiological findings and statistical considerations]. AB - The authors report the results of the retrospective study of 473 cases of spondylolysis observed on 3,505 plain films of the lumbar spine performed on athletes with low-back pain, from 1962 to 1992. The analysis of the results showed that: a) the incidence of spondylolysis was higher in athletes (13.49%) than in the general population (4-7%); b) the incidence of spondylolysis was higher in the distal portion of the lumbar spine (in 81.40% of cases L5 was involved); c) in 52% of cases spondylolysis was associated with spondylolisthesis -the latter of grade 1 according to Meyerding's classification in 74.39% of cases; d) bilateral and single-segment forms prevailed; e) the incidence of spondylolysis differed in the various sports according to the specific mechanical stimulation involved. PMID- 8190921 TI - [The detectability of osteoarticular lesions of the extremities on the television monitor]. AB - The diagnostic accuracy of the light-box reading of conventional (film screen) radiographs of the extremities was compared with that of the same set of images displayed on a 1 k x 1 k interactive monitor after laser digitization. 389 alterations (23 nondisplaced fractures, 129 soft-tissue calcifications and 237 articular bone erosions), identified by two experienced radiologists on 66 conventional radiographs, were the reference standard. ROC statistical analysis was performed on 1,556 observations expressed by four readers. The overall diagnostic performance of the two display modalities were substantially equivalent: no statistically significant differences resulted on the whole, but two individual readers performed better with conventional images. No overall nor individual statistically significant difference was reobserved for the subset of articular erosions either. Light-box reading of conventional radiographs allowed a higher number of calcifications in the soft-tissues and of proximal (carpal) abnormalities to be detected. Although our results indicate the overall high fidelity of monitor-displayed laser-digitized images, major improvements in the performance of digital diagnostic workstations are still required before adopting monitors for routine radiologic activity. PMID- 8190922 TI - [The diagnostic contribution of direct radiographic enlargement and of echography in the study of breast neoplasms]. AB - To compare the diagnostic value and the role of plain radiographic magnification and of ultrasonography (US) in breast cancer evaluation, 83 malignant tumors were studied with mammography, plain radiographic magnification and US. Microcalcifications were not included in our study. All tumors subsequently underwent histology or cytology. In our series, the malignant nature of the lesion was unquestionably proved in 53% of cases while a possible malignancy was suspected in 36% and a benign nature was incorrectly suspected in 11% of cases with mammography. The diagnostic value of plain radiographic magnification was compared with that of US; breast patterns, mammographic and clinical findings were considered. As for breast patterns, plain radiographic magnification was more accurate in evaluating fatty breast than both mammography and US, allowing the correct diagnosis of 58% of questionable mammographic findings, vs. 33% of US. On the contrary, US was more accurate in dense breasts, allowing the correct diagnosis of 77.7% of mammographic misdiagnoses vs. 33.3% only of plain radiographic magnification. As far as mammography is concerned, US was more accurate than plain radiographic magnification in the assessment of round masses (71.4% vs. 38.1%, respectively), whereas plain radiographic magnification was more accurate than US in stellate masses (100% vs. 92.7%, respectively). As far as clinical findings are concerned, plain radiographic magnification sensitivity was substantially the same in the assessment of symptomatic and asymptomatic lesions (91.5% vs. 89%, respectively), whereas US sensitivity was higher in symptomatic (97%) than in asymptomatic (69%) lesions. The rate of false-negative US diagnoses (14.4%) was higher than those of mammography and of plain radiographic magnification. Negative US findings must be considered with caution and are not sufficient to settle a radiologic doubt. PMID- 8190923 TI - [Mammographic screening. An analysis of the characteristics of interval carcinomas observed in the program in the province of Firenze (1989-1991)]. AB - The authors evaluated 30 interval cancers consecutively observed from 1989 to 1991 and compared them to 98 screening-detected cancers observed in the same period. Interval cancers have a more advanced stage (stage I = 13 lesions, stage II + = 17 lesions) with respect to screening-detected cancers (stage 0 = 10 lesions, stage I = 61 lesions, stage II + = 27 lesions). This finding seems unrelated to an intrinsically higher aggressivity of interval cancers (length biased sampling) which do not differ significantly from screening-detected cancers as far as histopathologic characteristics of prognostic value are concerned. Diagnostic delay due to technical or reading error (9 cases), to radiologically occult cancer in clear (10 cases) or dense parenchymal areas (11 cases) is most likely. This seems to be confirmed by the low frequency observed among interval cancers of easily visible lesions such as isolated microcalcifications (3% vs. 35%) or stellate opacities (13% vs. 31%), and by the higher frequency of opacities with irregular margins (57% vs. 26%) which are more likely masked by dense parenchyma. The chances of reducing interval cancer rate by attempting to increase sensitivity or by increasing screening frequency are discussed, as well as the possible negative consequences of such protocols in terms of cost-effectiveness. PMID- 8190924 TI - [High-resolution computed tomography study (HRCT) in so-called emphysema B. The correlations between the radiogram, the anatomical findings yielded by high resolution computed tomography and the clinico-functional assessment]. AB - The results are reported of a prospective study on 28 emphysematous patients with clinical, functional and radiologic correlations. Thirteen of 28 patients had type-B, the clinical "blue and bloater", emphysema. The grade of emphysema was investigated on conventional chest films and on HRCT scans, with a visual scoring system. Hyperinflation was assessed on conventional chest films and correlated with the extent of emphysema on HRCT images and with functional impairment. In our series, the extent of emphysema in B-type patients was markedly lower than in other patients of the same age, with the same smoking habits, dyspnea and functional impairment. Moreover, the incidence of centrilobular involvement was higher, though not statistically significant. The B-type exhibited more severe dilatation of subsegmental pulmonary arteries (76.9% vs. 20% p < 0.001) and a striking incidence of small airway disease (84.6% vs. 26.6%, p < 0.002). This findings may explain the radiographic pattern of "increased vascularity" seen on chest films. Bronchiolectasis and small airway wall thickening are much more frequent in type-B emphysema, together with patchy areas of ground-glass opacity and small peripheral nodules. A close correlation was observed between signs of small airway disease on HRCT images and functional clinical impairment. Thus, the small airway disease might eventually prove to be a more critical factor in causing functional and hemodynamic impairment in B-type emphysema than the actual extent of centrilobular emphysema. PMID- 8190925 TI - [Bronchiolo-alveolar carcinoma. The computed tomographic picture and histological correlations]. AB - Twenty-one CT examinations of 18 patients with a known bronchioloalveolar carcinoma in the lung were retrospectively reviewed to describe the CT features of bronchioloalveolar carcinomas. Surgical specimens were available in 13 cases in which CT-histologic correlation was also obtained. In 5 patients the diagnosis was made with cytology and confirmed with radiologic-clinical follow-up. Three patients were reexamined for relapses 6-20 months after the resection of a localized carcinoma. Carcinomas exhibited 3 radiologic patterns: a) solitary pulmonary nodule (11 cases), b) mass or pulmonary consolidation (3 cases) and c) multicentric or diffuse disease (7 cases). Solitary nodular bronchioloalveolar carcinomas were associated with irregular or spiculated margins in 9 of 11 patients. In some cases internal inhomogeneity due to bubble-like radiolucencies was demonstrated. At pathology, bubble-like radiolucencies correlated with air containing cystic spaces lined by neoplastic epithelium or patent and dilated bronchi. Some nodules exhibited linear and serpentine internal radiolucencies. Pathology demonstrated them to be consistent with patent intratumoral bronchioles (air bronchiologram) and air-containing neoplastic glandular spaces, respectively. In two cases a perinodular ground-glass halo was demonstrated surrounding the nodule (CT halo sign), due to perinodular lepidic tumor growth. Massive or ground-glass opacity involving a pulmonary segment or a lobe was another CT pattern of bronchioloalveolar carcinoma. An air bronchogram was usually demonstrated within the lesion. In the mucinous type of bronchioloalveolar carcinoma, pulmonary consolidations had a low CT value because of the large amount of intratumoral mucus. The diffuse type of tumor presented as multiple pulmonary nodules or multiple pulmonary consolidations, or both. In two cases multiple nodules were associated with carcinomatous lymphangitis. In conclusion, bronchioloalveolar carcinoma should be considered in the differential diagnosis of solitary pulmonary nodules, multiple pulmonary nodules and chronic alveolar opacities. The diagnosis of a bronchioloalveolar carcinoma is of great value since surgery can help nearly 70% of the patients at this stage recover. PMID- 8190926 TI - [Invasive pulmonary aspergillosis in oncological hematology: its pathogenesis and correlated radiographic picture]. AB - Invasive pulmonary aspergillosis (IPA) in the presence of hematologic malignancies is an increasingly common condition characterized by high morbidity and mortality. Plain chest films are a valuable tool for diagnosis but the radiologist must be familiar with the morphological features of the disease to interpret radiographic abnormalities and to differentiate IPA from opportunistic pneumonia. The chest films of 16 leukemia and IPA patients performed from January 1987 to September 1993 were reviewed. The natural course of infection from its early stage (nodular lesions) to the subsequent phases when eventual medullary recovery plays a critical role was thus traced. Our major finding was related to the histogenesis of primary pulmonary lesions: the most common features we observed--i.e., the spherical rather than triangular shape of necrosis areas, with no relationship to the pleura or scissural delimitation suggest that supposed ischemia from vascular infiltration cannot be the only pathogenetic factor of pulmonary injury, in spite of the well-known angioinvasivity of the fungus Aspergillus. PMID- 8190927 TI - [The torcular Herophili: the diagnostic pitfalls in TOF 3D magnetic resonance angiography]. AB - The authors report on a diagnostic pitfall which is often observed in magnetic resonance angiography (MRA) of intracranial vessels (time-of-flight 3D)--i.e., the absence of one of the two transverse sinuses. Fifty patients underwent MRA of the intracranial vessels with the TOF 3D (FISP) and the TOF 2D (FISP) techniques. Five patients were affected with sinus stenosis. MRA was performed with a 1.5-T superconductive magnet and a circular head coil. All patients underwent Magnetic Resonance Angiography with FISP 2D sequences (FA 40 degrees, TR 40 ms, TE 12 ms) acquired on coronal plane as well as FISP 3D (FA 15 degrees, TR 30 ms, TE 7 ms) acquired on axial plane. In the patients in whom FISP 2D sequences correctly demonstrated the whole confluence of sinuses, FISP 3D sequences always depicted the upper sagittal sinus, while the right transverse sinus was seen in 84.4% (38/45) of cases and the left transverse sinus in 24.2% (11/45) of cases. In the patients with a stenosis in the confluence of sinuses, FISP 3D sequences demonstrated two false-positive cases with respect to FISP 2D. The statistical analysis (McNemar test) of the results demonstrated the difference between 2D and 3D sequences in the detection of the two transverse sinuses to be statistically significant: p < 0.01 for the right transverse sinus and p < 0.001 for the left transverse sinus. In the study of the intracranial vessels (TOF 3D technique) the absence of one of the two transverse sinuses is suggestive of a diagnostic pitfall; the combination of 3D and 2D sequences answers this diagnostic question. PMID- 8190928 TI - [The echo-Doppler evaluation of the effects of glucagon on the portal flow in normal subjects. The premise for the loading test in portal hypertension]. AB - This study was aimed at evaluating the capabilities of Doppler US in the quantitative study of portal blood flow after glucagon administration in normal subjects. While its role in the qualitative study of portal hemodynamics is well known, it remains questionable whether Doppler US may be a valuable tool for the quantitative study of portal blood velocity. This may be solved by introducing, on a routine basis, meal tests which may provide a relative evaluation of the data. To date, these tests were based on the evaluation of blood flow velocity before and after a complete meal. For a more reliable test, we suggest that the meal be substituted with the i.v. administration of glucagon, which is known to play a major role in splanchnic hemodynamics during digestion. We examined 30 healthy volunteers and showed the possibility of a statistically significant evaluation of portal blood flow velocity before and after glucagon administration. After glucagon administration, blood flow velocity increased by 31.3% in 10 minutes, on the average, in all the healthy subjects. PMID- 8190929 TI - [The magnetic resonance estimation of the T parameter in the staging of tumors of the oral cavity and tongue. A correlation with postoperative data and preliminary echotomographic experience]. AB - Fifty-three patients with oral cavity and tongue tumors were studied with MRI, 18 with CT and 10 with US. MR results were compared with postoperative and clinical results relative to the T variable of the TNM classification of oral cavity tumors. MRI demonstrated 51 of 53 tumors; it was in agreement with surgery, relative to T, in 43 of 48 cases and with clinics in 5 of 5 cases. In 5 patients MRI understaged: two lesions were classified as T0 because the tumors developed on the surface (p T4, for alveolar ridge infiltration). Moreover, MRI staged another lesion as T2 instead of T3 because of its superficial component, while in 2 cases the infiltration of the cortical bone of the jaw was not demonstrated (T1 at MRI, T4 at p; T2 at MRI, T4 at p). MRI was reliable enough to evaluate the relationships between the lesions and the surrounding structures but it was limited in demonstrating superficial lesions and in evaluating the infiltration of the alveolar ridge and of the cortical bone of the jaw in the early stage. The use of gadolinium proved to be especially useful for the exact definition of the size of the lesions and of their relationships with the surrounding structures. CT proved better than MRI to evaluate bone involvement in one case, even though neither technique could identify bone involvement in another patient. US yielded accurate information on the presence of lesions, their size and relationships with midline and floor of the mouth muscles, while its demonstration of the relationships between tumors and bone structures was poor, especially relative to tumor spread outside the oral cavity. PMID- 8190930 TI - [Digital fluorography in gastroenterological radiology]. AB - The clinical value of two digital fluoroscopy systems not connected to a PACS was investigated and compared with that of conventional radiology. Some critical variables were considered: image intensifier diameter, image definition, examination time, acquisition speed, patient exposure and finally film consumption. The main problems in the use of the digital techniques consisted in the limited size of the examination fields, which was not big enough to demonstrate the whole colon during double contrast enema, and in the difficult representation of the actual size on the image printed on the laser films. Definition was considered as sufficient for GI examinations. The main advantages consisted in acquisition speed, allowing detailed examinations of cervical esophagus, cardias and fistulous tracts, reduced patient dose and finally the real time visualization of the acquired image on the TV monitor. PMID- 8190931 TI - [The role of magnetic resonance in characterizing focal liver lesions]. AB - 128 Magnetic resonance (MR) investigations of single or multifocal nodular liver lesions were retrospectively reviewed. All lesions had been identified, but not characterized, with ultrasonography (US). All the studies were performed with a 0.5-T superconductive magnet (Philips Gyroscan); spin-echo (SE) T1/proton density/T2-weighted and inversion recovery (IR) pulse sequences were used routinely. Characterization was attempted considering the following variables: a) lesion outline; b) the presence of some kind of capsular or pseudocapsular ring; c-d) homogeneity of signal intensity and its difference from surrounding liver parenchyma; e) possible central scar and its signal features; f) associated lesions (multifocal nodules, ascites, locoregional adenopathies, venous thrombosis). Diagnostic confirmation was obtained by means of biopsy (63 patients), of other imaging techniques (35 patients), or of clinical follow-up over 12 months at least (30 patients). Our results confirm high MR accuracy in the diagnosis of hemangioma (48/50 cases, 96% confidence) and even higher accuracy in focal fatty liver infiltration (9/9 cases, 100% confidence), thanks to some typical MR signal patterns on appropriate acquisition techniques--i.e., SE multiecho pulse sequences and IR sequences, respectively, with liver and fat signal nulling. Primary non-malignant focal liver lesions were identified mainly on a morphological basis (smooth roundish outline with/without capsular or pseudocapsular ring; central starlet scar; "basket" or "spoked wheel" patterns): these features allowed the correct identification of 5/7 focal nodular hyperplasia cases. On the other hand, in the absence of these typical morphological features and of specific MR signal changes, adenomas were misdiagnosed in all cases but one. The study of focal lesions in cirrhotic liver disease exhibited 66.6% confidence in the diagnosis of regenerating nodules, on the basis of their iso/hypointensity relative to liver on T2-weighted pulse sequences. Such a behavior seems to be due to intracellular iron loading, to small cell size and to thin vascular network, which are typical of cirrhotic regenerating areas. The diagnosis of hepatocellular carcinoma relies on both morphostructural features and possible associated lesions: in our series, 22/25 cases (88% confidence) were correctly identified. Indeed, this result was somehow influenced by the case history of the patients and by specific serologic indexes. Finally, MRI exhibited high sensitivity in the detection of focal liver involvement in neoplastic patients. However, the intrinsic range of variability and the lack of specificity of MR signal intensity, because of different histopathologic cell types, do not usually allow an unquestionable diagnosis to be made, especially for single lesions. PMID- 8190932 TI - [Dynamic single-slice computed tomography in the pretreatment evaluation of hepatocarcinoma in cirrhosis]. AB - Hepatocellular carcinomas (HCCs) are currently treated with surgery, transcatheter chemoembolization and percutaneous alcoholization; all methods require accurate in vivo anatomopathology of the lesion. The authors report their personal experience with 58 HCCs on cirrhosis which were studied with dynamic single-slice CT after the injection of water-soluble iodate contrast medium with automatic injector in a peripheral vein. Three semiologic patterns were identified according to lesion density on pre- and post-contrast images. The active portion of the lesion could be differentiated from the necrotic one in 100% of cases. Moreover, the necrotic lesion was differentiated from possible still viable tumor portions but with vacuolar degeneration phenomena. These findings allowed the authors to calculate the growth rate and the infiltrative capability of the single neoplastic masses. Finally, the dynamic evaluation of parenchymal enhancement allowed abnormal tissue vascularization due to arterioportal communication to be demonstrated in 7 cases. The authors conclude the dynamic single-slice CT allows the accurate assessment of HCC foci, of tumor tissue vascularization and of perilesional liver parenchyma. Therefore, dynamic single-slice CT is suggested as the technique of choice to study small HCCs before treatment. PMID- 8190933 TI - [Doppler color-echo and flowmetric evaluations in ovarian tumors in postmenopausal patients]. AB - The use of color Doppler techniques in transvaginal sonography (US) permitted the identification of some typical flowmetric patterns of malignant ovarian cancers, because of such characteristics of neoplastic vessels as no media in the vessel wall, the presence of A-V shunts, and so on. These features reduce vascular impedance, from which low pulsatility index and resistance index values result. Eighty-one patients with ovarian masses were examined: in 19 of them histopathology revealed malignant lesions in different stages. Eighteen of those lesions exhibited suspect transvaginal patterns; in one case only the US patterns suggested a benign lesion, which was a serous cystadenocarcinoma with thin and regular septa. In all the malignant lesions flow could be sampled in six sites at least; the lowest pulsatility index values, obtained by multiple samplings in the same lesion, were considered as the most representative of the histologic features of the lesion. The average of the lowest pulsatility index values in 18 of 19 malignant lesions was 0.75. In one case only (the only false negative in the series) the lowest pulsatility index value was 1.20. Doppler signals were detected in 58 of 62 benign lesions only and the average of the lowest pulsatility index values was 1.80. The only kind of condition with low pulsatility index was the inflammatory disease (all the 6 sampled cases). If we consider a pulsatility index < 1 as the cut-off value for malignant lesions, the sensitivity and the specificity of color Doppler US were 95% and 91%, respectively, in our series. The positive predictive value of the exam was 75% and its negative predictive value was 95%. PMID- 8190934 TI - [Tubular ectasia of the rete testis. The echographic aspects]. AB - Tubular ectasia of the seminiferous tubules of the rete testis is an uncommon benign condition which was only recently described. Its US pattern is typical and allows the disease to be distinguished from cystic tumors of the testicle. The condition was evaluated with US in 10 patients; all men were over 50 years old. US was performed with a 7.5-MHz linear probe. The lesion was unilateral in 7 and bilateral in 3 patients. It was always localized in the mediastinum testis and was associated with spermatocele in 5 cases and with testicular cysts in 4. On US scans, the condition presented with several tubular or rounded anechoic structures, mimicking a hypoechoic mass. In 5 men with 4-19 months' follow-up, no change in lesion size and structure was observed. Tubular ectasia was never assessed with biopsy or histology. Tubular ectasia of the rete testis shares several US features with testicular cysts and spermatocele, which are likely to have the same underlying mechanisms. This benign condition can be distinguished from true cysts and testicular tumors on the basis of US findings and its differential diagnosis is important to avoid unnecessary surgery. PMID- 8190935 TI - [The combination of extracorporeal lithotripsy and percutaneous nephrostomy in the treatment of obstructive ureteral urate calculi]. AB - The authors report their experience with combined percutaneous nephrostomy and extracorporeal shock-wave lithotripsy to treat obstructive uratic ureteral stones. The role of nephrostomy is stressed as a diagnosis and treatment method before, during and after lithotripsy. Thus, the method proved especially useful to drain obstructed kidneys and restore peristalsis, to evacuate septic urine, to facilitate the elimination of lithiasic fragments, to perform anterograde pyelography before, during and after lithotripsy and finally to allow pharmacological litholysis. Fourteen patients were successfully treated with combined extracorporeal lithotripsy and percutaneous nephrostomy and the results compared with those obtained with other techniques--e.g., ureteroscopy, whose value appears lower because the method requires general anesthesia and is more traumatic to the ureter. The authors conclude that combined extracorporeal lithotripsy and percutaneous nephrostomy make the best technique to treat obstructive uric acid stones thanks to their positive results, low invasiveness and to patients compliance. PMID- 8190936 TI - [The possibilities offered by the Siemens Therapy Data Management System in quality control in radiotherapy]. PMID- 8190937 TI - [Ossifying macroenthesopathy of the patellar tendon (telephone-receiver patella). A case report]. PMID- 8190938 TI - [Congenital diastasis of the pubic symphysis. A case report]. PMID- 8190939 TI - [The computed tomographic and magnetic resonance aspects of melorheostosis. A report of 2 cases]. PMID- 8190940 TI - [The high-resolution computed tomographic study of metastatic pulmonary calcifications. A case report]. PMID- 8190941 TI - [Biliary ileus of the sigmoid: its echographic diagnosis. A case report]. PMID- 8190942 TI - [Splenic lobulation simulating a gastric neoformation. The diagnostic value of echography]. PMID- 8190943 TI - [The role of echography and computed tomography in distinguishing benign cystic neoplasms of the pancreas and biliary tract. A report of 3 cases]. PMID- 8190944 TI - [Solitary left adrenal metachronous metastasis of hepatocarcinoma. A case report]. PMID- 8190945 TI - [The percutaneous treatment of a complex iatrogenic lesion of the biliary tract complicated by multiple peritoneal collections]. PMID- 8190946 TI - [The percutaneous retrieval of the fragment of a balloon catheter that ruptured in the biliary tract during endoscopic dilatation]. PMID- 8190947 TI - [The computed tomographic aspects in a case of aggressive mediastinal and retroperitoneal fibromatosis]. PMID- 8190948 TI - [The Langer-Giedion syndrome (TRP 2). A case report]. PMID- 8190949 TI - [Isolated renal aspergillosis in AIDS. A case report]. PMID- 8190950 TI - Duplex and color Doppler sonography of complications after percutaneous interventional vascular procedures. AB - Duplex and color Doppler sonography have proved to be excellent noninvasive modalities for evaluating complications of percutaneous interventional vascular procedures. Complications including hematoma, pseudoaneurysm, arteriovenous fistula, thrombosis, stenosis, and vessel occlusion are routinely diagnosed with Doppler sonography. Hematomas exhibit variable echogenicity and internal complexity but never demonstrate internal blood flow. A pseudoaneurysm is a contained extravasation of blood that, unlike a hematoma, maintains a patent vascular connection with the injured vessel. Puncture-related arteriovenous fistulas are false vascular channels between an adjacent artery and vein that demonstrate low-resistance arterial signal, high-velocity venous outflow, and variable flow patterns within themselves. Narrowing in a stent demonstrates high velocity turbulent flow with conventional Doppler and color aliasing with color Doppler techniques. Thrombus can be seen directly as a mural-based or luminal defect; however, it is often alterations in color flow dynamics, waveform characteristics, and flow velocities that permit conclusive diagnosis. Early experience in evaluation of stent stenosis in patients with transjugular intrahepatic portosystemic shunts suggests that low-velocity shunt flow indicates stenosis, likely related to the presence of low-resistance collateral pathways. Familiarity with both the interventional procedures and their possible complications facilitates prompt diagnosis and treatment. PMID- 8190951 TI - Patient confidentiality: radiologists can do better. PMID- 8190952 TI - Craniovertebral junction: normal anatomy, craniometry, and congenital anomalies. AB - The craniovertebral junction (CVJ) comprises the occiput, atlas, and axis and is visible in most magnetic resonance (MR) imaging studies of the brain. Craniometric measurements used in radiologic assessment of CVJ anomalies include the Chamberlain line, Wackenheim clivus baseline, Welcher basal angle, and atlantooccipital joint axis angle. Most anomalies of the occiput are associated with decreased skull base height and basilar invagination, the latter being a primary developmental anomaly in which the vertebral column is abnormally high and prolapsed into the skull base. Occiput anomalies include condylus tertius, condylar hypoplasia, basiocciput hypoplasia, and atlanto-occipital assimilation. Most atlas anomalies produce no abnormal CVJ relationships and are not associated with basilar invagination. These anomalies include aplasias, hypoplasias, and clefts of the atlas arches and "split atlas" (ie, posterior arch rachischisis associated with anterior arch rachischisis). Except for fusion anomalies, abnormalities of the axis are primarily confined to the odontoid process and are not associated with basilar invagination. These anomalies include persistent ossiculum terminale, odontoid aplasia, and os odontoideum. With the widespread availability of MR imaging, which is well suited for evaluating the CVJ because of its direct sagittal imaging capabilities, renewed understanding of CVJ anatomy and anomalies is important for all radiologists. PMID- 8190953 TI - Computer-aided instruction: the real issues. PMID- 8190954 TI - Magnetization transfer: theory and clinical applications in neuroradiology. AB - Magnetization transfer, a new technique for improving image contrast in magnetic resonance (MR) imaging, is based on application of off-resonance radio-frequency pulses and observing their effects on MR images, as well as measuring the signal intensity with and without application of the pulses (ie, magnetization transfer ratio [MTR]). MTRs can be used to detect changes in the structural status of brain parenchyma that may or may not be visible with standard MR techniques. Use of MTRs may allow subcategorization of multiple sclerosis lesions into those with very low MTR (demyelinated lesions) and slightly decreased MTR (edematous lesions). In cases of wallerian degeneration, use of MTRs appears to allow reliable detection of changes undetectable with MR imaging or even light microscopy. In cases of infection with human immunodeficiency virus, MTRs seem to indicate that the macromolecular structure of white matter remains intact until relatively late in the course of disease. In cases of metastatic disease, MTRs of brain lesions indicate structural changes beyond the extent of the lesions seen on standard MR images. These findings may be due to chronic edema, myelin loss, and perhaps previous undetected tumor. In addition to being a new method of providing contrast, the magnetization transfer technique enables semi quantitative, reproducible characterization of tissue and pathologic entities, which could substantially improve the specificity of MR imaging. PMID- 8190955 TI - Imaging of gallbladder carcinoma. AB - Although carcinoma of the gallbladder has a low overall prevalence, it is the most common malignant tumor of the biliary tract. Retrospectively, 59 cases of histologically proved gallbladder carcinoma were reviewed. The series consisted of 42 women and 17 men, ranging in age from 35 to 86 years. Clinical manifestations of gallbladder carcinoma include right upper quadrant pain, anorexia, weight loss, and jaundice. Radiologic findings included focal or diffuse thickening of the gallbladder wall (49%), a mass in the gallbladder fossa (37%), and an intraluminal mass (14%). Associated findings were cholelithiasis (64%), biliary duct dilatation (38%), invasion of the adjacent structures (67%), distant metastases other than those of the liver (3%), and porcelain gallbladder (4%). The histologic diagnoses were adenocarcinoma (90%) and squamous cell carcinoma (10%). Differential diagnoses include all conditions in which the gallbladder wall appears thickened. A general awareness of the radiologic features of gallbladder carcinoma enhances preoperative diagnoses. PMID- 8190956 TI - Imaging of the spleen: CT with supplemental MR examination. AB - Splenic lesions tend to be small or infiltrating and vary in size and configuration, making detection difficult, particularly without use of an organ specific contrast agent. The authors present a series of selected cases to show the value of computed tomography (CT) and magnetic resonance (MR) imaging in depiction of splenic disease. Six major categories are presented: (a) inflammatory disease, (b) splenic cysts, (c) infarction, (d) nonneoplastic and noninfectious diffuse splenic disease, (e) benign tumors, and (f) malignant tumors. CT attenuation of splenic tissue is homogeneous, typically measuring 40 60 HU on non-contrast material-enhanced scans. Splenic attenuation is normally 5 10 HU less than that of liver, a standard of reference used in evaluation of either hepatic or splenic disease. On T1-weighted MR images, the normal signal intensity of the spleen is less than that of hepatic tissue and slightly greater than that of muscle. On T2-weighted images, the spleen shows higher signal intensity, appearing brighter than the liver. CT is currently the choice for evaluation of the spleen; however, MR imaging may be increasingly used as newer pulse sequences and organ-specific contrast agents are developed. PMID- 8190957 TI - Imaging features of musculoskeletal brucellosis. AB - Brucellosis is endemic in certain parts of the world. Musculoskeletal involvement is the most common complication of brucellosis, and the spine is most frequently affected. Between November 1985 and March 1993, 334 patients with radiologically proved musculoskeletal brucellosis were seen. Involvement of the spine was either focal or diffuse, with a predilection to the lumbar region. Erosions and sclerosis in vertebral end plates, changes of inflammation at scintigraphy or magnetic resonance (MR) imaging, and intact disks were hallmarks of the focal form. Osteomyelitis of neighboring vertebrae, involvement of the intervening disk, and moderate epidural extension were features of diffuse brucellar spondylitis. The great majority of joints with scintigraphic evidence of disease demonstrated normal radiographic findings. Evidence of osteomyelitis or destructive arthritis was encountered in only a few cases. Although radiography is sufficient for demonstrating focal brucellosis, MR imaging is better for assessing diffuse disease. PMID- 8190958 TI - Congenital pulmonary venolobar syndrome revisited. AB - The term "congenital pulmonary venolobar syndrome" (CPVS) encompasses a number of congenital abnormalities of the thorax that often occur in combination. Major components of CPVS include hypogenetic lung, partial anomalous pulmonary venous return (this and the former are two of the most constantly occurring components), absence of a pulmonary artery, pulmonary sequestration, systemic arterialization of the lung, absence of the inferior vena cava, and accessory diaphragm. Minor components of CPVS include tracheal trifurcation, eventration and partial absence of the diaphragm, phrenic cyst, horseshoe lung, esophageal and gastric lung, anomalous superior vena cava, and absence of the left pericardium. Most patients with CPVS have no symptoms and require no therapy; however, surgical intervention is often necessary in infants with severe symptoms. The authors review the imaging findings in 29 patients with CPVS and review the literature concerning the diagnosis and management of this complex syndrome in order to improve the understanding of CPVS among radiologists and clinicians. PMID- 8190959 TI - Clarification on the anatomy and pathophysiology of posterior fossa cysts. PMID- 8190960 TI - Mammography quality assurance from A to Z. AB - Quality assurance (QA) refers to all planned, systematic activities that instill confidence that quality mammography is being performed. Quality control (QC) refers only to the technical aspects of the examination. Standardized labeling of mammograms and the format for mammographic reports are important parts of a QA program; recommendations for both have been published by the American College of Radiology. Minimum staff for a mammography service consists of a scheduler, technologist(s), medical physicist, and radiologist. The scheduler asks the patient questions to ensure that the appropriate examination is performed, gives the patient instructions, and asks the patient to complete a history questionnaire including a release form to obtain earlier mammograms. One certified, licensed technologist is designated to perform QC, which includes maintaining darkroom, screen, and view box cleanliness; reviewing processor performance, checked with sensitometer, densitometer, and phantom images; repeat analysis; analysis of fixative retained in film, darkroom fog, screen-film contact, and adequacy of compression; and visual inspection of equipment. A certified medical physicist performs equipment acceptance testing and annual QC visits thereafter. The radiologist oversees all aspects of the QA program, including selecting and regularly observing the technologists, selecting and meeting with the physicist, communicating results, ensuring patient follow-up, and assessing patient outcome data. The radiologist is ultimately responsible for image quality and the standard of patient care. PMID- 8190961 TI - Treatment of radiation exposure and contamination. AB - For treatment of radiation accident victims, procedures for handling trauma patients must be modified to ensure proper care and prevent contamination of hospital facilities and personnel. The radiation accident management plan should be instituted in advance. Exposure and contamination victims are treated differently. Exposed patients have sustained either partial or whole-body exposure but do not carry radioactive material; contaminated patients have also been exposed, but they have radioactive material either externally or internally and thus are continually exposed to radiation until the contaminant is removed. The treatment area and personnel must be protected with use of isolation, clean transfer techniques, and appropriate attire. After clothing has been removed, the patient's medical condition is assessed, stabilized, and treated. Samples from the affected areas, eyes, nose, and mouth are obtained for analysis and planning definitive treatment. For external contamination, the skin is washed with normal saline or mild detergent. Treatment of internal contamination is based on the isotopes involved and may include saturation of the crucial organ, dilution therapy, isotope displacement, or use of chelating agents. After a survey to ensure that no residual contamination remains, the patient is transferred to a care unit. Effects of exposure are seen over periods ranging from days to weeks to years, depending on the total dose received. Knowing the dose allows clinicians to predict what effects may ultimately occur. PMID- 8190962 TI - Noise content analysis in clinical digital images. AB - Most digital modalities in radiology use 12 bits precision to store the digital images. To determine whether all these bits contain useful information, a statistical method called the Moran test was used to measure the noise level in computed tomographic, magnetic resonance, and digital radiographic images. The test was performed on the bit planes of each pixel. After the noise level was estimated, the pixel data were separated into signal bits and noise bits, and image enhancement techniques were applied on the noise-bits-removed images to demonstrate that the removal of noise bits did not affect image quality. Preliminary results showed no noticeable difference between the original images and the noise-bits-removed images. PMID- 8190963 TI - Application of AMBER in single- and dual-energy digital imaging: improvement in noise level and display dynamic range. AB - The combination of computed radiography (CR) and advanced multiple beam equalization radiography (AMBER) was evaluated for both single- and dual-energy chest radiography. The improved signal-to-noise ratio found with CR and AMBER resulted in a better visualization of structures in the mediastinum and basal lung than that found with CR alone. For the central lung, no improvement was seen. Because of the compressed dynamic range with CR and AMBER, contrast on hard copies and video monitors could be high without a sacrifice in image latitude. Dual-energy images showed a considerably lower noise level. The combined use of AMBER and CR promises to overcome the dynamic range limitations of digital displays while improving signal-to-noise ratio. PMID- 8190964 TI - Color flow imaging. AB - The most recent technology change in diagnostic ultrasound is color flow imaging (CFI), which is a merging of gray-scale and motion-detection processing to produce an image that depicts soft tissue in gray scale and blood flow in color. Currently, CFI comes in three forms: synchronous signal processing, asynchronous signal processing, and time domain analysis. The first two employ Doppler-based principles, and the third uses direct measurements of blood flow displacement in the image. All three forms of CFI break the image into multiple sampling segments and process amplitude and motion information. A functional understanding of these technologies helps define and extend their roles in radiology as imaging tools. PMID- 8190965 TI - Bronchogenic carcinoma: radiologic-pathologic correlation. AB - Bronchogenic carcinoma is the leading cause of death from cancer in men and women in the United States. Although the cause of this malignancy is probably multifactorial, approximately 85% of lung cancer deaths are attributable to cigarette smoking. Patients may present with symptoms of airway obstruction caused by central tumors, symptoms related to direct tumor invasion of surrounding structures, or symptoms produced by distant metastases. There are four major cell types: adenocarcinoma, squamous cell carcinoma, undifferentiated large cell carcinoma, and small cell carcinoma. Adenocarcinoma and undifferentiated large cell carcinoma are generally peripheral lesions manifesting as solitary nodules or masses, whereas squamous cell carcinoma and small cell carcinoma are typically central and may manifest as hilar masses, atelectasis, or pneumonia. The prognosis for patients with bronchogenic carcinoma is poor, with an overall 5-year survival of 10%-15%. In general, patients with squamous cell carcinoma have the best prognosis, those with adenocarcinoma and undifferentiated large cell carcinoma have an intermediate prognosis, and those with small cell carcinoma have the worst prognosis. PMID- 8190966 TI - General case of the day. Transient lateral patellar dislocation (TLPD). PMID- 8190967 TI - Pediatric case of the day. Chiari III malformation. PMID- 8190968 TI - US case of the day. Hydatid cyst (Echinococcus granulosus) in the right lobe of the liver. PMID- 8190969 TI - Development and evaluation of the Active Treatment Client Rights Checklist. AB - The role of active treatment has been recognized as vital to the habilitation of persons with mental retardation; however, evaluating the provision of active treatment has been difficult. This study describes the development of the Active Treatment Client Rights checklist (ATCR), which was designed to facilitate the assessment, monitoring, and implementation of readily observable client active treatment services. This investigation provides an explanation of item content, initial reliability data (Phase I), and the results of implementation of the ATCR over a 2-year period in an ICF/MR facility with 29 living units serving nearly 500 clients (Phase II). The ATCR is highly reliable, valid, and useful in enhancing staff provision of active treatment. The most sensitive indicator of active treatment was shown to be related to frequency of functional interactions between clients and staff. PMID- 8190970 TI - Sentence combining as a technique for increasing adjective use in writing by students with autism. AB - A multiple-baseline across-subjects design was used to determine whether reinforcement alone or in combination with sentence-combining exercises would increase the number of descriptive adjectives used in daily writing samples by three adolescents with autism. The cumulative number of new adjectives (adjectives never before used by a student in the entire study) was also recorded. Experimental conditions were baseline, sentence combining, and maintenance. Writing sessions consisted of a 20-min worksheet period followed by a 20-min writing period. The addition of sentence-combining exercises increased the number of adjectives in the students' writing samples. Maintenance of this increase occurred in the absence of sentence-combining lessons and in the presence of reinforcement for use of adjectives. The addition of sentence combining exercises also increased the cumulative number of new adjectives, although new adjectives did not occasion reinforcement, and we had not expected their use to increase in students with autism without specific instruction. Maintenance of new adjective use also was demonstrated. Finally, for all three students, minimal terminable unit (T-unit) length, a measure that facilitates comparison with normative data, increased from baseline to maintenance, and independent raters judged writing samples written during maintenance as better than those written during baseline. PMID- 8190971 TI - The alliance of adaptive behavior and social competence: an examination of relationship between the scales of Independent Behavior and the Social Skills Rating System. AB - This study examined the relationship between ratings of adaptive behavior and social competence in a population of 208 students in kindergarten through third grade with a variety of disabilities using the Scales of Independent Behavior (SIB; Bruininks, Woodcock, Weatherman, & Hill, 1984) and the Social Skills Rating System (SSRS; Gresham & Elliott, 1990). Moderate yet statistically significant relationships between the SIB adaptive behavior scores and the SSRS social competence scores were found, with strongest correlations occurring between the SSRS and the Social and Communication subscale (r = .51) and Work Skills subscale (r = .60) on the SIB. Weak to near zero correlations were found between the SIB adaptive behavior scores and SSRS Problem Behaviors scores. This investigation provides new evidence for the concurrent criterion-related validity of both the SIB and the SSRS. PMID- 8190972 TI - Dynamic model for preventing mental retardation in the population: the importance of poverty and deprivation. AB - A dynamic simulation model is used to answer the question, "What is the most effective child health policy initiative for the prevention of mental retardation (MR)?" The impact of medical strategies is contrasted with social interventions to see how they affect the prevalence of MR in the general population. The model is based on data from four U.S. Census and California Vital Statistics reports (1960, 1970, 1980, 1990). An interstate comparison (California and South Carolina) uses 1990 data. The results of the simulations reveal that medical interventions to improve the developmental outcome of low birth weight (LBW) infants did not cause a reduction in the rate of MR in the population after a 24 year trial period. In contrast, reducing the proportion of children living in poverty who are exposed to environmental deprivation significantly decreased (10%) MR at the end of the model's time period. This analysis supports the view that long-term reduction in MR prevalence is attainable by modifying public policies that influence children's development. Effective MR prevention calls for public policy committed to multifaceted health and educational services for both affected parents and their young children. PMID- 8190973 TI - Attention deficit-hyperactivity disorder among mentally retarded children. AB - Teachers completed the Connors' Teacher Rating Scale (CTRS-39) on 100 boys assigned to one of four groups based on an IQ screen and scores on a DSM-III-R checklist of the symptoms for Attention Deficit-Hyperactivity Disorder (AD-HD). The groups included children rated high on AD-HD, mentally retarded children, mentally retarded children rated high on AD-HD, and a normal control group. Using the CTRS-39, there were no significant differences between the normal IQ AD-HD group and the mentally retarded AD-HD group on all but one of the factors. Mentally retarded children in general were found to be more anxious than their normal peers, whereas normal IQ AD-HD children were rated higher than the other groups on the Asocial factor. Implications of these data and future directions are discussed. PMID- 8190974 TI - Positive side effects in the treatment of SIB using the Self-Injurious Behavior Inhibiting System (SIBIS): implications for operant and biochemical explanations of SIB. AB - The rate of self-injurious head hitting was reduced using contingent electric shock delivered via the Self-Injurious Behavior Inhibiting System (SIBIS). Positive side effects indicating an improved affective state and increased interaction with the environment were documented. Treatment gains were maintained at a 1-year follow-up assessment. The consistent reports of positive affective side effects from successful treatment studies using SIBIS and contingent electric shock are noted. Implications for current operant-based theories of SIB based on the communication function of SIB and endogenous opiate mechanisms are discussed. PMID- 8190975 TI - [Methodology of surveys in animal epidemiology]. AB - In the present paper, the authors review the methodological bases of surveys, both descriptive and analytical, used in animal epidemiology. They give a comprehensive definition of the main terms applied to epidemiology as well as of the method used to evaluate the quality of these surveys. PMID- 8190976 TI - [Nervous syndrome in sheep on the Ivory Coast. I. Epidemiological and clinical study, methods of diagnosis and treatment]. AB - The ovine nervous syndrome in Cote-d'Ivoire is similar to the cerebrocortical necrosis (CCN) due to vitamin B1 deficiency. All classical symptoms of CCN were observed (locomotor ataxia with subsequent paralysis) and histological evidence for polioencephalomalacia was given. However, the circumstances for occurrence of the disease are very different in the two cases, i.e. CCN is a disease encountered in young fattening ruminants in developed countries while the ovine nervous syndrome is mainly observed in Cote-d'Ivoire during the dry season when pastures become sparse and dry and when the feed supply is insufficient. Thus, the main cause, which is rather univocal, is a sudden decrease in the nutritive value of the diet, but the accurate etiopathogenesis of the disease has not yet been determined. In a flock where 10-30% of the animals are ill, the mortality may reach 80-90%. No classical biochemical assays were specific enough to establish a precise diagnosis of the nervous syndrome. However, it should be pointed out that the CK (creatinine kinase) values very regularly rose and that the ASAT (aspartate aminotransferase) values were high in 75% of the cases. In the present African field conditions, the precise diagnosis is based on the efficiency of the vitamin B1 treatment and, for the dead animals, on the histological analysis of the brain. PMID- 8190977 TI - Epidemiological survey of the Maedi Visna (MV) virus in Syrian Awassi sheep. AB - Awassi sheep sera from all the Syrian provinces were tested for antibodies against the Maedi Visna (MV) virus using the Agar Immuno-diffusion test. Eighty seven animals out of 1,445 tested, showed positiveness (6%) to MV glycoprotein 135. The infection was detected in most provinces except in the Southern provinces of Damascus, Sweida and Konaitra. Use and quality of folds and rainfall were considered as factors influencing Maedi Visna distribution. The infection could be related to losses in sheep production and especially to the reduction in survivability (i.e. annual percentage of sheep not dying or culled). PMID- 8190978 TI - Epidemiology of Salmonella infections in Trinidadian livestock farms. AB - Faeces of 689 diarrhoeic and non-diarrhoeic livestock were examined for salmonellae and the antibiograms of isolates were determined. Twenty-nine (4.2%) animals were positive for Salmonella. The highest prevalence was detected amongst calves with 14 (4.8%) of 293 found positive and the lowest prevalence in kids with none of 18 sampled shedding salmonellae. Twelve (4.1%) of 294 piglets and 3 (3.6%) of 84 lambs tested were positive for Salmonella. There were no statistical differences (P > or = 0.05; chi 2) between animal semi-intensively managed (4.4%) and those intensively kept (4.3%), between diarrhoeic (5.0%) and non-diarrhoeic (3.3%), between females (5.2%) and males (3.4%). Nine serotypes were isolated with a predominance of S. hadar, S. gaminara and S. typhimurium in calves, piglets and lambs, respectively. Two serotypes, S. kinshasa and S. virchow are reported for the first time in animals in the West Indies. All Salmonella strains were sensitive to ampicillin and gentamycin whereas resistance was high to tetracycline (40.0%), triple sulphur (30.0%) and streptomycin (26.7%). PMID- 8190979 TI - Anthrax in humans and camels in the Sudan with reference to the disease in the country. PMID- 8190980 TI - [Epidemiology of Cowdria infection in Senegal. I. Study of the transmission and infection level in Amblyomma variegatum (Fabricius, 1794) in the Niayes region]. AB - The authors report the results of research on infection rates of Amblyomma variegatum nympha and imago populations by Cowdria ruminantium in the Niayes region as well as on the transmission rates of A. variegatum by the various stases. The experiments were carried out on sheep from the Sahelian zone where the vector tick is not endemic. The infection rate, estimated by inoculating sheep with ground ticks, gave the following prevalences: t = 13.3% for nymphae and t = 1.2% for adults. The transmission rates calculated on the basis of a daily count of nymphae and adults (which were marked), gave the following minimum values: 11.1% for nymphae and 9.5% for imagos. In-station studies, using nymphae and imagos gorged at their larval or nymphal stase on infected sheep, showed infection rates of 100%. The transmission by nymphae and imagos originating from the same groups amounted to 80%. Intrastadial transmission assays by males and females previously gorged on sheep in hyperthermia, were unsuccessful. PMID- 8190981 TI - [Epidemiology of Cowdria infection in Senegal. II. Results of sero epidemiological follow-up studies]. AB - The authors report the results of sero-epidemiological monitoring of Zebu, Diakore and Ndama cattle in the Sahel, Niayes and North Guinea zones, respectively. Calves aged 0-3 or 3-6 months were subjected to blood sampling every three months for a period of 20 months. In the Niayes and North Guinea zones, the immunofluorescence test showed that about 70% of 0-1 month old calves reacted positively to the Cowdria ruminantium antigen, whereas the prevalence was 92% between 3 and 6 months. After the age of 6 months, the results were 100% positive. In the Sahelian area, the prevalence of the infection was null. Results obtained with a sample of about 100 adult cattle from the Sahel, Niayes, North Sudan and North Guinea zones, showed a good correlation between positivity rates and the size of Amblyomma variegatum populations. PMID- 8190982 TI - [Epidemiology of trypanosomiasis caused by T. evansi in camels in mali: results of parasitological and clinical survey]. AB - An epidemiological study of trypanosomiasis was conducted in the rearing areas of dromedary camels in Mali. According to the parasitological and clinical surveys performed, the overall infection rates were 9.5% (29/305) in Western Sahel (region I) and 4.5% (28/627) in the areas of Tombouctou and Gao (region II). The proportion of contaminated herds was 55% in region I and 68% in region II and in some herds the infection rate exceeded 50%. The surveys showed a trend for increasing parasitological prevalence with age. While it was almost nonexistent in young camels less than one year old, it increased with age and reached a maximum in 2 to 5-year old camels. The authors showed that the infection has a significantly negative effect on PCV and on the overall status of the animals, confirming the pathogenicity of Trypanosoma evansi in dromedary camels. This trypanosome is almost the only species detected in the dromedary camel in Mali and it does not seem to cause infections in other animals reared in the same environment. PMID- 8190983 TI - [Effect of a nutrition factor on neonatal pathology: results of a retrospective survey on the mangrove supply to dromedary calves in the Republic of Djibouti]. AB - The authors present a retrospective survey carried out in 23 camps of nomadic afars from Obock area (Djibouti) and concerning the traditional utilization of different types of forage from lagoon (mangrove) in relation with some of the diseases observed, particularly on calves. Four types of mangrove running are described: supply of mangrove twigs to calves less than one year old in camps and mangrove grazing for the adults; permanent feeding of mangrove associated with complementation; occasional supply of mangrove by cutting the twigs; permanent distribution of mangrove without complementation. The risk to observe diseases, namely loss of appetite, lameness, skin diseases and paralysis is 4.28 time higher when diet complementation is missing. PMID- 8190984 TI - [Introduction to ecopathology. The development of ecopathological surveys in tropical milieu: constraints and prospects]. PMID- 8190985 TI - [Ecopathological survey on pneumopathies in goats during the dry cold season in Chad: methodological aspects]. AB - The authors describe the methodology used in an ecopathological survey of goat pneumopathies in periurban area of N'Djamena (Chad) during the dry, cold season of 1991-1992. The choice of farms was made after a typology survey. A total of 3,500 small ruminants (85% of goats) belonging to 60 farms were identified and the performance and health of the animals examined from August 1991. The protocol used for collecting information and the strategy applied to the analysis of data were based on conceptual pre-models of analysis corresponding to the 3 observations scales used, i.e. goat, concession flock, day flock. The survey took place from December 1991 to March 1992. The difficulties of the statistical interpretation of the data, are emphasized. The biological significance of the risk factors is discussed. Measures for obtaining improvements should take into account the cost/profit ratio and the technical and financial possibilities of the farmers. PMID- 8190986 TI - [Descriptive epidemiology of caprine abortion in traditional breeding in Northeastern Brazil. A retrospective survey of female reproductive performance]. AB - A retrospective survey of goat reproductive performance was carried out in a sample of 1,317 females kept in traditional rearing conditions in a small semi arid region of Northeastern Brazil. The study involved 2,155 kiddings and the analysis of the abortion problem was made according to retrospectively measured factors such as year of kidding, doe age, kidding order, age at kidding and type of farm. The methodology used appealed to the farmer's memory. The results showed that abortion was a constant problem in the region (13%). It affected more frequently young females and mainly at first kidding (20.7%), irrespectively of age. The year of kidding seemed to influence the abortion rate, but this was probably due to the large climatic variability. Abortion rates varied according to farms, but the difference was not significant. This variability could be explained by the variety of edaphic conditions of the region studied. PMID- 8190987 TI - [Decision making in animal health]. AB - The aim of epidemiology is to provide the necessary data to implement animal health programmes and to control the diseases. In too many occasions, especially in developing countries, informations are still incomplete and the decision is often difficult. Using the model developed by SIMON for firm management, the authors describe a decision making process calling for the personality of the decision makers when data are incomplete (limited rationality model). The different steps of the process (intelligence, design, choice, implementation and control) are discussed. PMID- 8190988 TI - [Nervous syndrome in sheep on the Ivory Coast. II. Economic impact, trials and cost-benefit analysis of preventive plans]. AB - The clinical and epidemiological aspects of the ovine nervous syndrome in Cote d'Ivoire were presented in the first part of this paper and the disease was considered to be similar to the cerebrocortical necrosis as related to vitamin B1 deficiency. The economic losses by this disease being 1,500 to 2,000 F CFA (30-40 FF) per animal and per year, it seemed to be very important to consider its prophylaxis. A programme involving a daily injection of 100 mg of thiamine chlorhydrate throughout the dry season proved to be very efficient. In addition, if excluding the cost of the injection, this programme appeared to be beneficial to the farmer. When including only the price of the product, the profit to cost ratio of the programme was 4.8 (thiamine at 400 F CFA) to 30.6 (thiamine at 66 F CFA). The other profit earning criteria, i.e. the differential actualized net value and the induced gains, showed the same positive effect of this prophylaxis programme. However, it should be emphasized that the nervous syndrome in sheep mainly remains an accident due to a poor flock management. Hence, to prevent this disease the farmer should correctly adapt the rearing methods to the intensification of the production. Nevertheless, as the accurate etiopathogenesis of the syndrome remains to be elucidated and as the daily injection of the product to all animals of the flock represents an important constraint, research should be pursued to solve a problem which seems to affect the whole region. PMID- 8190989 TI - Effect of mecillinam on peptidoglycan synthesis during the division cycle of Salmonella typhimurium 2616. AB - The effects of mecillinam, ampicillin and cephalexin on peptidoglycan synthesis in Salmonella typhimurium 2616 have been studied at equivalent concentrations or "isoactivities". Using antibiotics at isoactivities allows a direct comparison of the biochemical effects of different antibiotics. When mecillinam was added at different times during the division cycle at a concentration that produced 50% inhibition of peptidoglycan synthesis in an exponential culture over a short period of time, the inhibition of synthesis was greatest in the newborn cells and least in the dividing cells. Antibiotic competition experiments showed that mecillinam preferentially bound to penicillin-binding protein 2 in S. typhimurium 2616. High performance liquid chromatography analysis of the residual peptidoglycan synthesized in the presence of mecillinam showed an unexpected increase in pentapeptides and a significant increase in cross-linking. Other antibiotics added at equivalent activities did not show an increase in cross linking. PMID- 8190990 TI - Phenotypic characterization of human and animal biotypes within the species Porphyromonas gingivalis. AB - Ninety-nine strains of Gram-negative black-pigmented anaerobic rods, grown on Todd-Hewitt blood agar plates, were identified and characterized according to a typing scheme including UV fluorescence, catalase, trypsin-like and haemagglutinating activities, biochemical tests with the ATB 32A kit, and gas liquid chromatography. To determine the taxonomic position of the Porphyromonas gingivalis biotypes, 68 strains (31 of human origin and 37 of animal origin) were compared to 31 strains of closely related species or of uncertain generic status. Most animal strains were isolated in our laboratory by subculturing samples from the oral cavity of five mammalian species (bear, cat, coyote, dog and wolf). Those strains differed from human P. gingivalis strains in that they were positive for catalase, beta-galactosidase and glutamyl-glutamic acid arylamidase; from Bacteroides macacae by more rapid pigmentation, positive haemagglutination, failure to produce propionic acid, and negative alpha-galactosidase; and from Bacteroides salivosus by more rapid pigmentation, positive haemagglutination and failure to produce propionic acid. These data demonstrate that phenotypic heterogeneity within the taxon P. gingivalis can be resolved into two biotypes, each corresponding to a human source or an animal source. PMID- 8190991 TI - Randomly amplified polymorphic DNA analysis confirms the biotyping scheme of Porphyromonas gingivalis. AB - The application of the arbitrarily primed PCR (AP-PCR) procedure to generate randomly amplified polymorphic DNA (RAPD) fingerprints for the study of the taxon Porphyromonas gingivalis was investigated. Nine human strains and seven animal strains of P. gingivalis as well as eighteen strains other than P. gingivalis were analysed. Four nanomer primers of random sequence were evaluated for their ability to distinguish genetic diversity. Three primers generated RAPD fingerprints that allowed the sixteen strains to be differentiated; two of the primers yielded species-specific markers, and two of the primers permitted biotype distinction. Cluster analysis of the RAPD fingerprints revealed two major phenetic groups that matched the human and animal biotypes. Our results indicate that AP-PCR (i) can generate strain-specific fingerprints, (ii) confirms genetic heterogeneity and the biotype grouping of the P. gingivalis taxon, and (iii) enables identification of potential genetic markers at the species, biotype and subtype levels and is thus a promising tool for bacterial systematics. Our results also underline the potential of AP-PCR for epidemiological studies of periodontal pathogens. PMID- 8190993 TI - Supplement 1992 (no. 36) to the Kauffmann-White scheme. PMID- 8190992 TI - A new genomic species in Borrelia burgdorferi sensu lato isolated from Japanese ticks. AB - Five Borrelia strains (Ika2, HO14, Cow611C, 0612 and F63B) isolated from Ixodes ovatus ticks in Japan were analysed by DNA-DNA hybridization experiments, ribotyping, pulsed-field gel electrophoresis and protein electrophoresis. DNA relatedness set these strains in a new genomic species within the Borrelia burgdorferi complex; this species appears to be restricted to Japan and could be non-pathogenic for humans. The ribotype and pulsotype of strain Ika2 were atypical of the new genomic species. PMID- 8190994 TI - Expression of P.69/pertactin from Bordetella pertussis in a baculovirus/insect cell expression system: protective properties of the recombinant protein. AB - The surface antigen P.69/pertactin of Bordetella pertussis has been expressed using the polyhedron promoter of baculovirus in cultured insect cells. Either full-length or truncated prn DNA was used to express P.69 pertactin. The full length gene gave rise to low levels of P.93 precursor protein, some of which was processed to P.69. The shortened prn expressed P.69 pertactin directly at levels up to 3.5 mg per litre. P.69 vaccinated animals were protected against aerosol challenge with virulent B. pertussis bacteria. PMID- 8190996 TI - PCR-mediated DNA typing of Campylobacter jejuni isolated from patients with recurrent infections. AB - The polymerase chain reaction (PCR) and two primers aiming at the enterobacterial repetitive intergenic consensus (ERIC) and arbitrary DNA sequences, respectively, were used to fingerprint the genomic DNA of 24 Campylobacter jejuni strains isolated from five patients with recurrent C. jejuni infections. Results were compared with biotyping and serotyping. The latter two methods, when combined, distinguished 9 different types, whereas PCR-mediated DNA analysis discriminated 14 different patterns. For six strains, the results of PCR-mediated typing led to different interpretations. This method is proposed as an additional tool to further discriminate between C. jejuni strains that appear related by conventional typing methods. In view of its rapidity and simplicity, this method is a potential candidate to replace the relatively slow and laborious conventional methods. However, further study is needed to assess the sensitivity and specificity of PCR-mediated DNA analysis and to investigate the usefulness of this method as an epidemiological tool in outbreaks of Campylobacter infections. PMID- 8190995 TI - Cloning and nucleotide sequence analysis of immunodominant heat-shock protein of Yersinia enterocolitica. AB - Yersinia enterocolitica, a highly antigenic 60-kDa protein, designated cross reacting protein antigen (CRPA), is a member of the chaperonin-60 family of molecular chaperones. The gene encoding CRPA was cloned, expressed and sequenced. A partial library from Y. enterocolitica 0:3 genomic DNA was constructed in vector pUC19 and was screened by the immunoreactivity to monoclonal antibody 1A4, which has specificity for a species-specific epitope on the CRPA molecule. The crpA gene region consists of a putative two-cistron operon encoding proteins of 549 and 97 amino acids. The operon structure was led by a consensus heat-shock promoter sequence. Homology searches using the derived amino acid sequence have revealed that CRPA is 88.2% identical to GroEL of Escherichia coli. CRPB, another protein encoded by the operon, shows extensive sequence homology, 91.8% identical to GroES of E. coli which is a member of chaperonin-10. PMID- 8190997 TI - Molecular typing of thermotolerant species of Campylobacter with ribosomal RNA gene patterns. AB - Ribosomal RNA gene restriction patterns (ribopatterns) of 72 strains representing Campylobacter jejuni (subspecies jejuni and doylei), C. coli, C. upsaliensis and C. lari including the urealytic (UPTC) biovar were determined using four common restriction endonucleases (HaeIII, HindIII, PstI and PvuII). The relative effectiveness of these enzymes for general molecular typing of the thermotolerant campylobacters was assessed. Ribotypes (HaeIII) were defined on the basis of computer-assisted numerical analysis. For C. jejuni, C. coli and C. lari, the HaeIII ribopatterns provided a high level of typability and discrimination, with patterns that were reproducible and easy to code for numerical analysis. There was evidence of diversity within three of the HaeIII types, and PstI ribopatterns proved the most reliable for detecting such differences. C. upsaliensis also could be ribotyped with HaeIII, but HindIII, PvuII and PstI were less satisfactory for this species. For such campylobacters, the HindIII ribopatterns generally were complex and difficult to compare, and the PvuII profiles provided the least discrimination. We conclude that the choice of restriction endonuclease is of critical importance when applying ribotyping to different species of Campylobacter. HaeIII ribopatterns were the most effective means of typing strains of different thermotolerant species of campylobacters and, when combined with PstI ribopatterns, offered a highly discriminatory basis for molecular typing. PMID- 8190998 TI - Molecular characterization of enterotoxigenic Escherichia coli (ETEC) isolated in New Caledonia (value of potential protective antigens in oral vaccine candidates). AB - The role of enterotoxigenic Escherichia coli (ETEC) in childhood diarrhoea in New Caledonia was demonstrated in previous epidemiological works. This study was undertaken in order to characterize these strains and to determine whether bacterial components of current vaccine candidates (toxin, colonization factor antigens, O:H antigens) would be useful in our region. A total of 24 ETEC strains were studied: 5 strains produced heat-labile enterotoxin, 17 strains produced heat-stable enterotoxin (9 STp and 8 STh), and 2 strains produced both toxins (1 LT/STp/STh and 1 LT/STh). E. coli strains were screened for the presence of genes encoding for enterotoxins (DNA dot blot and Southern hybridization assays); results obtained with probes were closely correlated and were in agreement with biological assays. No two ETEC strains possessed similar plasmid profiles, and DNA sequences encoding for enterotoxins were located on plasmids ranging from 58 to 75 MDa. The O:H (O1:H-,O2:H7, O6:H16, O25:H-, O27:H7, O28ab:H9, O52:H10, O64:H5, O70:H-, O78:H12, O88:H25, O99:H6, O101:H-, O126:H12, O166:H30) serotypes are presented (all the strains were typable, but some ETEC serotypes were unusual). By using antisera against colonization factor antigens (CFA) I and II, results showed that 9 of the 24 ETEC strains expressed CFA (2 CFA/II and 7 CFA/I). These strains possessed high bacterial surface hydrophobicity. Fifteen ETEC did not possess CFA; among these, 11 did not exhibit high hydrophobicity or show haemagglutination activity. Four of the 15 CFA-negative strains exhibited high hydrophobicity (two O64:H45, one O70:H- and one O88:H25) but no haemagglutination in the presence or absence of mannose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8190999 TI - Differential scanning calorimetry investigations on LPS and free lipids A of the bacterial cell wall. AB - Differential scanning calorimetry (DSC) was used to investigate the thermal stability and behaviour of the lipopolysaccharides (LPS) of the outer membrane of Gram-negative bacteria and their lipid portion. DSC curves of LPS show thermal features between 200 and 129 degrees C (depolymerization) and between -13 and -36 degrees C (cooling phase transition). Both effects were related to the relative strength of the linkage types in the O-chain structure and to their capacity for intermolecular hydrogen bonding. DSC curves of lipids A show endotherm peaks between 40 and 24 degrees C, around 15 degrees C and between -23 and -4 degrees C. Based on these effects, strong differences in thermal behaviour can be observed between that of Brucella and Vibrio cholerae on the one hand, and that of Escherichia coli and Shigella flexneri on the other. Fluidity of the acyl chains and lyotropism, which are important parameters in expression of biological activities, are discussed using the above data. To explain some properties, fluidity could be related to the temperature of the gel<==>liquid crystalline (beta<==>alpha) phase transition, which occurs at physiological temperature. Nevertheless, fluidity could be related to temperature of the previous thermal effect (between 6 and 20 degrees C), for which a softening or partial melting of the sample has been evidenced. The thermal effect measured between -23 degrees C and -4 degrees C indicates a greatly reduced water concentration of lipid A from Brucella, thus explaining its early fusion process and its activity by means of hydrophobic interactions. PMID- 8191000 TI - Quantitative investigations into the elimination of in vitro-obtained spores of the non-pathogenic Clostridium butyricum strain CNRZ 528, and their persistence in organs of different species following intravenous spore administration. AB - Before the Clostridium tumour assay can be applied to the diagnosis of cancer, we sought to investigate--within the framework of a biopharmaceutical safety test- the organ persistence of test spores of Clostridium butyricum CNRZ 528. We found that non-pathogenic spores obtained in vitro, like pathogenic native spores, escape phagocytosis in various organs up until about 2 years, as tested by anaerobic cultures. The elimination of spores depended on the species of animal, the spore dose and the organs investigated. In rabbits, one week after injection, we recovered clostridial spores from blood and spleen cultures more rarely than from liver and lung. The half-life of blood clearance in patients was one day or, at half the spore dose, two days. That deep tissues of healthy animals are not normally sterile became evident in rabbits after sporadic isolation and characterization of non-administered saccharolytic and proteolytic clostridial species. During a 10-year observation period, the rate of obtainment of viable spores by in vitro cultures lessened; however, for administration of the spores in clinical phase I and phase II studies, the spore quality was acceptable. PMID- 8191001 TI - Acute arthritis of cats associated with feline calicivirus infection. AB - Twelve specific pathogen-free cats were infected either by intra-articular inoculation or by contact exposure to one of two strains of feline calicivirus (FCV), either F65, a field strain originating from an outbreak of lameness in a group of cats, or a vaccine strain. Following either route of exposure, both strains induced signs typical of FCV infection including oral and nasal ulceration, conjunctivitis and ocular discharge. These signs were of equal severity for both virus strains, but overall, following either route of infection, F65 induced more severe disease than the vaccine strain, with marked pyrexia, lethargy and lameness. Vaccine virus only induced a relatively mild lameness following intra-articular inoculation. Gross pathological and histopathological lesions were seen in some of the joints, but again changes were more severe in the F65-exposed cats. Virus was isolated from both normal and affected joints from both groups of F65-exposed cats, and from a joint from each cat inoculated intra-articularly with vaccine virus. Mild transient lameness was also seen in one of two control cats inoculated intra-articularly, but no pathological changes were seen or virus isolated from joints. A cDNA probe used in RNA dot blot hybridisation experiments was found to be specific and more sensitive than virus isolation in detecting FCV in selected tissues. This may be useful in future studies on the pathogenesis of FCV disease and in studies on viral persistence in FCV carriers. PMID- 8191002 TI - Pharmacokinetics of N-methylglucamine antimoniate after intravenous, intramuscular and subcutaneous administration in the dog. AB - The pharmacokinetic profile of antimony in dogs was defined by administering it intravenously, intramuscularly and subcutaneously as N-methylglucamine antimoniate at a dose of about 25.65 mg of antimony kg-1 bodyweight. The results showed a different half-life for the three routes of administration: 20.5, 42.1 and 121.6 minutes for the intravenous, intramuscular and subcutaneous routes, respectively; peak time values (Tmax) were also different for the intramuscular (90 to 120 minutes) and subcutaneous (210 to 240 minutes) injection. The apparent bioavailability of antimony was > 100 per cent for the intramuscular and 100 per cent for the subcutaneous routes. The data obtained showed a relevant difference in the behaviour of the drug in the dog in comparison to that in humans. PMID- 8191003 TI - Latent papillomavirus infection in cattle. AB - During a long term experiment designed to identify the contribution of bovine papillomavirus type 4 (BPV-4), environmental mutagens and immunosuppressants to the development of carcinomas of the upper alimentary tract of cattle, there was evidence of latent papillomavirus infection. Papillomatosis-free animals, when immunosuppressed either by feeding bracken fern or by azathioprine treatment, developed skin warts containing either BPV-1 or BPV-2. Skin warts appeared also in an immunocompetent animal at sites of damaged skin. It was concluded that the animals harboured latent papillomavirus which was reactivated by immunosuppression and/or physical trauma, causing skin warts. Papillomavirus DNA was also detected in lymphocytes of both experimental and control animals, suggesting that one of the sites of latency may be the circulating lymphocyte. PMID- 8191004 TI - Effect of Pasteurella haemolytica infection on alpha 1-acid glycoprotein and albumin concentrations in serum and subcutaneous tissue chamber fluid of calves. AB - Thermoplastic tissue chambers were implanted subcutaneously in the paralumbar fossae of 10 calves. Concentrations of alpha 1-acid glycoprotein (AAG) and albumin in serum and subcutaneous tissue chamber fluid were measured before and after inoculation of Pasteurella haemolytica into tissue chambers. Two months after implantation, serum and tissue chamber fluid samples were collected and all tissue chambers were then inoculated with P haemolytica. Additional serum and chamber fluid samples were collected two, four, six and 10 days after inoculation. The concentrations of AAG and albumin in the samples were measured by radial immunodiffusion assay and the bromcresol method, respectively. P haemolytica inoculation resulted in an increase in the serum and chamber fluid AAG concentrations and an increase in chamber fluid albumin concentrations, suggesting that the proportion of drugs bound to serum and interstitial proteins may be affected by P haemolytica infection. PMID- 8191005 TI - Gastric emptying of four liquid meals in pony foals. AB - Water, saline and a saline/Intralipid mixture (lipid concentration 1.25 per cent) emptied very rapidly from the stomach in neonatal pony foals, and obeyed an apparently exponential pattern. Cisapride did not significantly modify the emptying of the saline/Intralipid mixture. Equine milk emptied more slowly. The data indicated that the lipid component of milk was not an important factor. Milk caused deviation from an exponential pattern in two of four foals: an initial lag phase appeared, which could represent a phase of intragastric processing. However, the rate was still rapid compared with results from human infants. PMID- 8191006 TI - Serological evidence for antigenic relationships between Ehrlichia canis and Cowdria ruminantium. AB - The sera from dogs experimentally infected with Ehrlichia canis reacted at very similar titres in indirect fluorescent antibody (IFA) tests with E canis and Cowdria ruminantium antigen. In Western blots these sera reacted strongly with the immunodominant antigens of E canis (27 kDa) and C ruminantium (25 and 32 kDa). The dogs experimentally infected with C ruminantium showed no clinical evidence of infection, though the presence of organisms in the blood was demonstrable, for up to two weeks after inoculation, by a polymerase chain reaction. The sera from these dogs were also reactive with both organisms in the IFA tests, but the antibody titres were four- to fivefold higher with C ruminantium than with E canis antigen. In Western blots, these sera reacted strongly with the 25 and 32 kDa antigens of C ruminantium but weakly with the 27 kDa antigen of E canis. These results provide strong evidence that the immunodominant antigens of E canis and C ruminantium contain cross-reacting epitopes. PMID- 8191007 TI - Effects of proligestone and megestrol on plasma adrenocorticotrophic hormone, insulin and insulin-like growth factor-1 concentrations in cats. AB - This paper reports changes in adrenocorticotrophic hormone (ACTH), insulin and insulin-like growth factor-1 (IGF-1) concentrations in cats from a previously published study. The cats were given oral megestrol acetate (MA, 5 mg once daily for 14 days), subcutaneous proligestone (PRG, 100 mg on two occasions one week apart) or subcutaneous saline (1 ml as for PRG). In the cats given saline (n = 6), basal ACTH, insulin and IGF-1 did not change significantly throughout the following seven weeks. The cats given MA (n = 7) developed significant suppression of plasma ACTH concentrations and hyperinsulinaemia during treatment and for two to four weeks after MA dosage ceased. In the cats given PRG (n = 7), plasma ACTH concentrations were not significantly altered although three cats had markedly suppressed values for some time after PRG treatment had ceased. Serum insulin concentrations were not significantly altered in the PRG-treated cats. The results suggest PRG may be a preferable alternative to MA in some situations. PMID- 8191008 TI - Comparison of antigenic and pathogenic properties of Mycoplasma iowae strains and development of a PCR-based detection assay. AB - The six reference strains of Mycoplasma iowae (I, J, K, N, Q and R) and 12 field strains, most of them isolated from turkeys, were studied with a growth inhibition test and a dot immunobinding test with rabbit antisera to the different serovars of M iowae, 16S rDNA gene amplification by polymerase chain reaction, and pathogenicity for chicken or turkey embryos. Antigenic tests tended to be strain specific and showed that most field strains were closely related to serovars K or N. The two pairs of primers chosen in 16S rDNA guided the amplification of 332 base pairs (bp) or 892 bp fragments from all the M iowae strains tested. All the field strains tested were highly pathogenic for turkey embryos. PMID- 8191009 TI - Experimentally induced proliferative enteritis in hamsters: an ultrastructural study. AB - Hamsters, three weeks old, were dosed orally with suspensions of intracellular bacteria grown in rat enterocyte tissue culture cells IEC-18, which had been infected with suspensions of intracellular bacteria derived from the lesions of proliferative haemorrhagic enteropathy occurring naturally in two pigs. Each bacterial strain, identified as Ileal symbiont intracellularis, was passaged in the cell lines once, twice or five times, collected with the cells and used as inocula. Ten of 16 hamsters dosed with 916/91 passaged one or five times developed lesions of proliferative enteritis. In these 10 hamsters, marked hyperplasia of ileal enterocytes associated with numerous intracellular curved bacteria was detected. An ultrastructural study of epithelial cells in the ileum of affected hamsters showed numerous intracellular bacteria in the cytoplasm. Similar bacteria were not seen in unaffected animals. Intracellular bacteria were usually seen in groups and could appear as electron dense or in a more electron lucent form. These bacteria were clearly seen to enter cells from the intestinal lumen, via endocytic vacuoles at the brush border. There was rapid breakdown of the entry vacuoles, leaving bacteria free in the cytoplasm where division was usually observed. These bacteria were often seen in close association with normal or distended mitochondria and rough endoplasmic reticulum. PMID- 8191010 TI - Replication of border disease virus in ovine lymphocytes and monocytes in vitro. AB - Adherent and non-adherent mononuclear cells obtained from the peripheral blood of normal sheep supported the in vitro replication of a non-cytopathic and a cytopathic strain of Border disease virus (BDV) with no apparent cytopathic effects. There was a significant rise in virus titres in adherent mononuclear cells (monocyte) and non-adherent (lymphocyte) cultures infected with both non cytopathic and cytopathic strains of BDV 24 hours after inoculation. Peak virus titres of 5.36 log10 TCID50 ml-1 were recorded in adherent samples incubated for 48 hours while peak titres of 6.17 log10 TCID50 ml-1 were recorded in lymphocyte culture after 72 hours of incubation. Both the non-cytopathic and the cytopathic strains of BDV produced significantly higher titres in non-adherent (lymphocyte) cultures than in adherent (monocyte) cultures (P < 0.001) but the replication in adherent cells was faster than in nonadherent cell cultures. The addition of virus on both types of mononuclear cell cultures had no effect on cell viability but it had a significant inhibitory effect on the blastogenic responses of lymphocytes to phytohaemagglutinin. PMID- 8191011 TI - Effects of experimental infection with border disease virus on lymphocyte subpopulations in the peripheral blood of lambs. AB - Experimental infection with Border disease virus was characterised by significant changes in the total numbers of leucocytes and neutrophils, and in the proportions and numbers of the different lymphocyte subpopulations. Three days after experimental infection there was significant leucopenia due to lymphocytopenia and neutropenia (P < 0.001). The lymphocytopenia and neutropenia lasted for up to seven days after inoculation. The lymphocytopenia was due to a reduction in the number of both T cells and B cells. During the early period of infection, the reduction in T cells was mainly due to a reduction in the number of OvCD4+ and T-19+ lymphocytes as the number of circulating OvCD8+ cells was not significantly affected. The cells expressing the OvCD4 and OvWC1 epitopes returned to pre-inoculation values 10 and 14 days after inoculation, respectively. In contrast, during the same period, the number of T cells expressing the OvCD8 molecule became significantly higher than the corresponding pre-inoculation values. There were no significant changes in all the T cell subsets in the control lambs. PMID- 8191012 TI - Squamous cell carcinoma of the feline thymus with widespread apoptosis. AB - The present report documents a case of squamous cell carcinoma originating from the thymus of a 12-year-old short-haired male cat. The tumour had metastasised to the sternal lymphoid tissue and to the left lung. To the authors' knowledge, thymic carcinoma has not been reported in domestic animals. Furthermore, extensive apoptosis was observed in the tumour mass. PMID- 8191013 TI - Immunosuppression in sheep experimentally infected with Ehrlichia phagocytophila. AB - The effect of tick-borne fever (TBF) on antibody formation and lymphocyte proliferation in sheep was studied following experimental infection with Ehrlichia phagocytophila. All infected sheep developed fever within three to four days. The sheep recovered clinically within eight days. Both infected and non infected control sheep were immunised twice with different antigens, that is, on days 9 and 35 following the experimental infection. The levels of antibodies produced against tetanus toxoid and influenza virus in the infected sheep were significantly lower than in the control animals. The findings indicated that a TBF-infection may impair both primary and secondary antibody responses for up to six weeks. Immunisation with Actinomyces pyogenes resulted in significantly higher antibody titres in the TBF-infected group than in the control group, as measured by an enzyme-linked immunosorbent assay (ELISA). It is believed that TBF induced neutropenia may lead to increased exposure to A pyogenes-antigens and thereby enhance antibody production. Antibodies to E phagocytophila were measured by the indirect fluorescent antibody test and by an ELISA. The inoculated sheep responded with the formation of antibodies to E phagocytophila at one week (P < 0.025), and showed a peak response at four weeks (P < 0.0005) after inoculation. The antibody titre decreased between four and six weeks, but was still high at six weeks (P < 0.0005). The lymphocyte responses to phytohaemagglutinin (PHA) concanavalin A (Con A) and pokeweed mitogen (PWM) were lower than in the control group and this difference was significant at most time points after infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191014 TI - Differential stressor effects on the concentrations of cortisol, prolactin and catecholamines in the blood of sheep. AB - Adult wether sheep (n = 8) were subjected to 60 minutes of psychological (isolation) or physical (transport simulation/standing in water) stress, or a control handling procedure in the home pen. Blood samples were taken before and during these treatments and the plasma concentrations of cortisol, prolactin, noradrenaline and adrenaline determined. All the stressors significantly increased plasma cortisol concentrations (P < 0.001) whereas only transport simulation increased prolactin secretion (P < 0.005). Noradrenaline concentrations showed little change in response to the various treatments, with the exception of isolation which produced a small non-significant increase (P < 0.08). All the stress procedures stimulated adrenaline release within the first 10 minutes but the most marked effects were seen after transport simulation and isolation, both of which induced a significant increase throughout the treatment period (P < 0.01). PMID- 8191015 TI - Relationship between the indicators of performance and the weight of pneumonic lesions from pigs at slaughter. AB - Lungs from pigs at slaughter were examined and the extent of the lesions was estimated as the percentage by weight of the lung affected by pneumonia in relation to the weight of the whole lung. Linear regression analyses of mean daily gain in liveweight and days to slaughter on the percentage by weight of pneumonic lung were performed. Within a range between 3.32 and 74.55 per cent for the weight of pneumonic lung, a 10 per cent increase in the weight of pneumonic lung was associated with a decrease in mean daily gain of 31.4 g and a 13.2-day increase to slaughter at 104.2 kg liveweight. When subgroups of pigs were evaluated by farm of origin, significant associations between indicators of performance and pneumonia for pigs from only one of the farms were found. PMID- 8191016 TI - Use of indirect immunofluorescence and western blotting to assess the role of circulating antimyocardial antibodies in dogs with dilated cardiomyopathy. AB - The presence of circulating anti-heart IgG and IgM autoantibodies was assessed by indirect immunofluorescence and by probing Western blot transfers of normal canine myocardial proteins separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis with samples of sera from dogs with dilated cardiomyopathy (n = 27) and from healthy control dogs (n = 20). No difference was demonstrated between the two groups using either method. Sera taken from the affected dogs at three monthly intervals throughout the course of the disease showed no change at all in the pattern of reactivity. The results of this study suggest that indirect immunofluorescence and the probing of Western blot transfers of a crude preparation of normal canine myocardium with canine sera will demonstrate too many apparent autoantigens for the technique to identify unique, disease associated autoantibodies. PMID- 8191018 TI - Measurement of gastric emptying of water in foals by impedance epigastrography. AB - Impedance epigastrography was used to measure gastric emptying rates on two occasions in each of three foals. After smoothing of the raw data, emptying of water appeared to obey an exponential model. The mean emptying rate constant (SEM) was 0.171 +/- 0.038 min-1 (mean emptying half time 4.9 +/- 1.0 min). PMID- 8191017 TI - Regulation of mammary gland macrophage tumour necrosis factor-alpha production with interferon-gamma. AB - Recombinant bovine interferon (rBoIFN)-gamma was found to modify the production of tumour necrosis factor (TNF-alpha) production by lipopolysaccharide (LPS) stimulated mammary gland macrophages. Alveolar macrophages isolated from bovine mammary glands were incubated with 0, 1, 10, 100 or 1000 U of rBoIFN-gamma either three hours before or three hours following stimulation with LPS. The level of TNF-alpha production was not affected when macrophages were treated with rBoIFN before LPS stimulation. In contrast, macrophages treated with 10, 100 or 1000 U of rBoIFN after stimulation with LPS produced significantly lower concentrations of TNF-alpha when compared with non-treated cultures and those treated with only 1 U of interferon (IFN)-gamma. These results indicate that IFN-gamma is capable of down-regulating the production of TNF-alpha by a local macrophage population. The ability of IFN-gamma to modify the production of TNF-alpha is dependent on the timing of administration relative to LPS exposure. The significance of these findings is that under some circumstances, low dose administration of IFN-gamma may be directly responsible for down-regulation of acute phase inflammatory responses which may prevent pathological alterations to host tissues during endotoxaemia. PMID- 8191019 TI - A latex agglutination test for the qualitative detection of Clostridium perfringens epsilon toxin. AB - A latex agglutination test (LAT), with a neutralisation control, has been developed for the detection of Clostridium perfringens epsilon toxin. The LAT readily detects the toxin qualitatively in the intestinal contents of animals suspected of dying from enterotoxaemia. When the LAT was compared with an enzyme linked immunosorbent assay (ELISA), the LAT proved easy to perform and had a sensitivity and specificity only slightly less than the ELISA. PMID- 8191020 TI - Effects of a change in phosphorus requirement on phosphorus kinetics in the sheep. AB - An experiment was carried out to examine the effects of a change in P requirement, achieved by intravenous calcium loading, on intestinal phosphorus absorption, salivary phosphorus secretion and faecal endogenous phosphorus loss in adult sheep fitted with a rumen and duodenal cannula. Isotope dilution was used to measure faecal endogenous phosphorus loss while 103ruthenium phenanthroline and 51chromium-ethylenediamine tetra-acetic acid were used to measure duodenal phosphorus flow. The infusion of calcium chloride led to an increase in calcium and phosphorus retention, the increase in phosphorus retention being due to a reduction in faecal phosphorus excretion as a result of enhanced intestinal phosphorus absorption and reduced faecal endogenous phosphorus excretion. There was, however, no change in duodenal phosphorus flow or in the amount of phosphorus estimated to have been added to the digesta via the saliva. These results suggest that the increase in phosphorus retention seen in response to an increase in phosphorus requirement is largely achieved through an increase in intestinal absorptive efficiency and not through any reduction in endogenous phosphorus secretion into the gut. PMID- 8191021 TI - ETCO2 monitoring during low flow states: clinical aims and limits. AB - End-tidal carbon dioxide concentration in the expired air (ETCO2) is measured with different technologies. ETCO2 allows the global evaluation of three main body functions: metabolism, circulation and ventilation. If two of these parameters are held constant, changes in ETCO2 reflect a variation of the third. Thus, ETCO2 is now widely used as a reliable monitoring device in various clinical settings. In the past years several studies proposed ETCO2 as a noninvasive monitor for the evaluation of therapeutic efforts during low-flow states, and especially during cardiopulmonary resuscitation. However, recent laboratory and clinical investigations demonstrated that various pharmacological and physical interventions may influence ETCO2. Especially, the use of the CO2 generating buffer NaHCO3 increase and alpha-adrenergic agents constantly decrease ETCO2. Thus, although ETCO2 remains a necessary tool during anaesthesia, it may loose the potential for prediction of survival when monitoring the resuscitative efforts during cardiopulmonary resuscitation. PMID- 8191022 TI - Outcome of cardiopulmonary resuscitation and predictors of resuscitation status in an urban community teaching hospital. AB - Medical records of all expired patients as well as all patients designated on billing logs as having received cardiopulmonary resuscitation (CPR) during a 6 month period were reviewed. Patients were considered to have been 'coded' if they were found unresponsive and if the advanced cardiac life support (ACLS) protocol of the American Heart Association (AHA) was subsequently initiated. Of 105 patients who received CPR, 98 died during their hospital stay. Of the seven remaining patients, four had undergone coronary by-pass graft surgery, one was discharged in a persistent vegetative state, one died during an admission 2 months later, and one patient was transferred to another institution where he died. Various factors were studied in an effort to determine how patients on whom resuscitation was attempted differed from those who died without ever having received CPR. Patients who underwent CPR at least once during their hospitalization were more likely to have had cardiac diagnoses on admission (P < 0.001), to have been postoperative (P = 0.02), to have been admitted to a monitored bed on admission (P < 0.001) to have received more days of intensive care (P < 0.001) and to have received more specialist consultations (P = 0.004). Patients not receiving CPR were more likely to have had a primary diagnosis of neoplastic disease (P < 0.001), stroke or intracranial hemorrhage (P = 0.02) or dementia (P < 0.001). Age, race, or gender did not differ significantly between the two groups. PMID- 8191023 TI - Willingness of male homosexuals to perform mouth-to-mouth resuscitation. AB - BACKGROUND: Providing mouth-to-mouth resuscitation (MMR) during cardiopulmonary resuscitation (CPR) is a proven effective lifesaving procedure. However, the perceived risk to the rescuer of contracting infectious diseases, especially acquired immunodeficiency syndrome (AIDS), by performing MMR on a possibly human immunodeficiency virus (HIV) positive individual is probably affecting the number of people willing to perform MMR. Physicians and nurses constitute a major part of citizen cardiopulmonary resuscitation (CPR) responders and serve as CPR educators and resource personnel. Currently, the fear of physicians and nurses of contracting infectious disease has dampened their willingness to perform MMR, and thus has reduced the number of strangers who will receive MMR. Homosexual males, like the medical community, have an increased perceived risk of acquiring infectious diseases, especially AIDS, and have been the target of intense educational efforts concerning the transmission of HIV. By (a) determining the willingness of various groups to perform MMR, (b) elucidating the factors which affect their willingness to perform MMR, and (c) comparing this willingness to the actual, not perceived, risk of acquiring HIV by performing MMR, either appropriate changes can be made to educate people in the performance of MMR, by informing them of the actual risks of contracting infectious diseases, or alternative methods of resuscitation, involving 'lay-on' masks, can be recommended. Thus the willingness of homosexual males to perform MMR was determined and compared to the previously determined actual reluctance of the medical community to perform MMR in similar hypothetical scenarios. METHODS: During interviews, 200 male homosexuals in Los Angeles were asked to assume that they knew how to perform CPR and MMR and to indicate how they would respond to four hypothetical cardiac arrest scenarios. These scenarios included cardiac arrests of a child, a trauma victim, a young man in a gay neighbourhood, and a victim of unknown history. Demographical data concerning the respondents was also obtained. RESULTS: Of the homosexual men surveyed, 93 and 85% stated they would perform MMR on a stranger of unknown history, if they, the rescuer, were HIV negative or positive, respectively, (P < 0.001). Similarly, a high percentage of the presumed HIV negative and HIV positive respondents stated a high willingness to perform MMR in response to hypothetical cardiac arrest scenarios involving a trauma victim, a child, and a young man in a gay neighbourhood. CONCLUSIONS: The willingness of male homosexuals to perform MMR is high, in contrast to the general reluctance of internists and medical nurses to perform MMR in the same outpatient scenarios. The different perceived risks of male homosexuals and physicians acquiring infectious diseases by performing MMR is probably responsible for the difference in willingness of these two groups to perform MMR. The high perceived risk of acquiring infectious diseases due to performance of MMR currently held by physicians in general may be lowered by increasing educational efforts. CPR courses should (a) discuss actual and perceived risks of acquiring infectious diseases by MMR, (b) discuss and weigh a small, and possibly not valid, risk of contracting an infectious disease while performing MMR on a victim, and (c) emphasize techniques involving 'lay-on' barrier masks. The availability of effective 'lay-on' barrier masks' should also be increased. PMID- 8191024 TI - Epinephrine absorption following endotracheal administration: effects of hypoxia induced low pulmonary blood flow. AB - To investigate the effects of hypoxia-induced decreased pulmonary blood flow on the trans-pulmonary absorption of epinephrine, we measured pulmonary blood flow and arterial plasma tritium counts per minute following endotracheal [3H]epinephrine administration in six chronically instrumented newborn lambs. The lambs were ventilated alternately with room air and with an hypoxic gas mixture sufficient to decrease pulmonary blood flow to approximately 50% of baseline values. Using this model, we found that hypoxia-induced low pulmonary blood flow did not lead to lower concentrations of epinephrine following endotracheal administration, but rather higher concentrations (P < 0.03). In all six lambs, counts per minute of tritium were higher following administration during low pulmonary blood flow. There was a negative correlation between pulmonary blood flow and arterial plasma tritium counts per minute (r = -0.64, P < 0.03). We conclude that trans-pulmonary absorption of epinephrine is not decreased during times of hypoxia-induced low pulmonary blood flow. These data lend support to the clinical practice of intratracheal epinephrine administration during neonatal resuscitation. PMID- 8191025 TI - Student nurses can defibrillate within 90 seconds. An evaluation of a training programme for third year student nurses in the use of an automatic external defibrillator. AB - Automatic external defibrillators (AEDs) provide a means of reducing the response time in cardiac arrests but policies based on their use must take into account the costs of retraining. These depend on the level of retention of skills over time. This paper describes the retention of skills by student nurses following a training programme on the use of AEDs in cardiac resuscitation. Sixty-three student nurses were studied at intervals of 1 week, 1, 3 and 6 months following training. There was a slight deterioration in skills at 1 week and 1 month but the scores returned to the baseline level at 3 months and remained there. We conclude that there is now a case for a major study of the use of nurse-operated AEDs in the hospital setting. PMID- 8191026 TI - Training St John Ambulance volunteers to use an automated external defibrillator. AB - The key to improving survival from pre-hospital cardiac arrest lies in reducing the time interval between onset of cardiac arrest and defibrillation. Placing automated external defibrillators at strategic points in the community could potentially reduce this time interval, but would necessitate widespread training in defibrillation for lay people in addition to health care workers. There are unanswered questions regarding the ability of lay people to acquire and retain this skill when the training programme is, by necessity, very brief, (otherwise it would not be possible to train large enough numbers of people) and the skill is used infrequently. In this study, nurse and lay volunteer first-aiders were taught to use an automated external defibrillator, either by a 2-h, or a 4-h course, and their skills were assessed at training, and at 3 and 6 months afterwards. Using stringent assessment criteria, 54% of volunteers passed the assessment at every session. Little difference in acquisition or retention of skills between the nurse and lay volunteers, and the 2- and 4-h course groups was found. It is concluded that brief training in defibrillation for volunteer first aiders is feasible. PMID- 8191027 TI - Prognostic markers in patients with severe accidental hypothermia and cardiocirculatory arrest. AB - The aim of this retrospective study was to investigate whether plasma potassium, pH and activated clotting time (ACT), obtained from a central venous blood sample immediately after admission to hospital, could predict outcome in patients with severe accidental hypothermia and cardiocirculatory arrest. Twenty-two patients rewarmed with cardiopulmonary bypass were studied retrospectively (12 patients after avalanche accidents, seven patients after cold water submersion and three patients after prolonged exposure to cold). In 12 patients stable spontaneous circulation could not be restored. In 10 patients stable spontaneous circulation could be restored. Two of these 10 patients survived long-term. Plasma potassium, central venous pH and ACT were clinically useful prognostic markers in hypothermic arrest victims after avalanche accidents: a plasma potassium value exceeding 9 mmol/l, a pH equal to or less than 6.50 or an ACT exceeding 400 s was seen in patients in whom spontaneous circulation could not be restored. Plasma potassium, central venous pH and ACT were of only limited prognostic value in hypothermic arrest victims following cold water submersion or prolonged exposure to cold. In hypothermic arrest victims after cold water submersion a central venous pH as low as 6.51 on admission did not exclude long-term survival. Moderate and severe hyperkalemia in arrest victims after prolonged exposure to cold need not necessarily indicate postmortem autolysis. A decision to continue or terminate resuscitation cannot be based on laboratory parameters. Nevertheless, our data suggest that plasma potassium, central venous pH and ACT on admission can be used to identify hypothermic arrest victims in whom death preceded cooling. If several hypothermic arrest victims are admitted simultaneously after avalanche accidents, these 3 parameters can help not to waste limited cardiopulmonary bypass facilities for patients with no hope of survival. PMID- 8191028 TI - The causative rhythm in out-of-hospital cardiac arrests witnessed by the emergency medical services in the Heartstart Scotland Project. AB - Out-of-hospital defibrillation has been shown to improve survival in out-of hospital cardiac arrests. The maximum performance of defibrillation-based systems is dependent on the proportion of cardiac arrests due to tachyarrhythmias. We reviewed 4248 reported arrests in the Heartstart Scotland database. We identified 3489 arrests due to cardiac or unknown cause. From this group we selected 258 cases known to be conscious on arrival of the crew. We were able to retrieve electrocardiographic data on the period within 2 min of the arrest in 106 cases. The first recorded rhythm at the arrest was ventricular fibrillation in 64%, ventricular tachycardia 4%, bradycardia in 28% and electromechanical dissociation in 4%. Defibrillatory shocks were delivered to 96% of patients in ventricular fibrillation and 60% of these patients survived. None of the patients with bradycardic arrests survived. Preceding chest pain was noted in 79% of patients subsequently developing ventricular fibrillation as the cause of arrest compared to only 37% of those suffering bradycardic arrests. It would appear that public awareness of the importance of early contact with the emergency services after the onset of chest pain could substantially improve the survival from out-of hospital arrests. PMID- 8191029 TI - Establishing a resuscitation model in rabbits with closed-thoracic cardiopulmonary by-pass. AB - This study aims to establish an animal model of resuscitation in rabbits by using closed-thoracic cardiopulmonary by-pass (CTCPB). The rabbits were randomly divided into four groups according to cardiac arrest times which were 8, 10, 12, and 15 min. Neurologic outcome and blood lactate were determined within 150 min after resuscitation. It was indicated that the rabbits' neurologic functions were progressively injured with prolonged cardiac arrest time. The threshold of circulatory arrest time that induced a vegetative state in the rabbits was between 10 and 12 min. There were no significant differences in cardiac resuscitability among the four groups, as was so for plasma lactate, although it increased significantly from the control levels. The establishment of a small animal model of resuscitation by using CTCPB, and the problems in dealing with it are also described and discussed in detail in this paper. Our experience indicated that this is a simple, convenient, and economical animal model for the study of resuscitation. PMID- 8191030 TI - Effect of hemorrhagic shock duration on the activity of nuclear Ca2+/Mg(2+) dependent DNA-endonucleases in canine cerebral cortex. AB - A direct correlation between the duration of arterial hypotension (40 mmHg) and the activity value of nuclear Ca2+/Mg(2+)-dependent DNA-endonucleases was revealed in dogs exposed to hemorrhagic shock. Thus, an increase in the activity of endonucleases was significant after 2 h of arterial hypotension. During that period there activity amounted to 4149 +/- 295 units/mg of protein instead of 2839 +/- 231 units/mg protein in the control (P < 0.01). With the prolonged hemorrhagic shock, the activity of DNA-endonucleases continued to increase. By 4 h of hemorrhagic shock it reached 5021 +/- 443 units/mg protein and by 6 h, 8661 +/- 338 units/mg protein which was three times the control values (P < 0.01). An electron-microscopic study of the structure of neuron nuclei karioplasm showed that by 2-4 h of hemorrhagic shock some neurons showed reduced chromatin content, and the nuclear matrix had clarified with the formation of electron-translucent empty zones. We think that the sharp increase in the nuclear endonuclease activity and the subsequent endonucleolysis can be regarded as a pathogenetic factor in the destructive processes taking place in the nuclei of cortex neurons during prolonged periods of hemorrhagic shock. PMID- 8191031 TI - Intracerebroventricular injection of bombesin (6-14) restores blood pressure in hemorrhaged rabbits. AB - Rabbits were intracerebroventricularly (i.c.v.) injected by bombesin (6-14) (100 micrograms) or saline (control group) immediately after acute hemorrhage (28 ml/kg body wt.). Bombesin (6-14) normalized the blood pressure and maintained it at the normal level during 30-40 min but it did not alter the dynamics of heart rate and body temperature. It has been proposed that action on the central regulation of vascular tension by intrathecal injection of bombesin or some active analogs might avoid the need for infusion therapy or minimize the infusion volume. PMID- 8191032 TI - The eyes, the brain, and cardiac resuscitation. PMID- 8191033 TI - Why do we need a large multi-centric database for clinical out-of-hospital cardiac arrest research? PMID- 8191034 TI - The use of the laryngeal mask airway in CPR. AB - The laryngeal mask airway (LMA) was used within the hospital in 50 cardiac arrest cases during cardio-pulmonary resuscitation (CPR). The LMA was inserted mainly by junior anaesthesia staff members with no previous experience with its use. The LMA was easily inserted providing a clear and unobstructed airway in 98% of the patients with clinically satisfactory ventilation and very good blood gas values. No signs of regurgitation or aspiration were detected. PMID- 8191035 TI - Mechanical behaviour of the canine respiratory system at very low lung volumes. AB - We studied the changes in dynamic elastance and resistance of the respiratory system in 6 supine, anaesthetized, paralysed, tracheostomised and open chested dogs. Tracheal pressure (Ptr), tracheal flow (V) and 3 alveolar pressures (Palv by alveolar capsule) were measured continuously for 20 min at 5 levels of positive end expiratory pressure (PEEP) between 0.1 and 0.5 kPa. The lungs were inflated to total lung capacity (TLC) at the start of each recording period. Lung elastance (EL) and resistance (RL) were estimated by fitting the equation Ptr = RLV + ELV + K to the measured data for each breath by multiple linear regression (V = volume, K = constant). Airway resistance (Raw) was obtained from the difference between Ptr and Palv. EL increased progressively in the 20 min following lung inflations. The increase in EL over this time was about 45% of its baseline value at a PEEP of 0.1 kPa compared to an increase of only about 10% at a PEEP of 0.5 kPa. In contrast, RL changed very little over the recording period at all levels of PEEP. At low levels of PEEP Palv often bore no resemblance to Ptr indicating that significant airway obstruction or closure had occurred. These results suggest that the increase in EL at low PEEP was primarily due to the accretion of airspace closure, and that nonlinear tissue mechanical properties were responsible for the lack of change in RL. PMID- 8191036 TI - Simulation of exchanges of multiple gases in bubbles in the body. AB - This communication introduces a system of equations, for numerical solution, which simulates the generation, growth, and decay of bubbles. The system is an advance over previous works because it allows for simultaneous diffusion of any number of gases. Our purpose for developing the system is to gain insight into the bubbles that occur in the body in decompression sickness (DCS). We validate the calculation system by matching observed data of DCS bubbles and of large subcutaneous gas pockets in rats. We demonstrate how a temporary supersaturation and bubble formation can occur without change of ambient pressure when there is a change in the inert gas being breathed. With exposures to hypobaric environments, such as when astronauts work in space, simulations show that O2, CO2, and water vapor add appreciably to volume of bubbles and affect the diffusion of inert gas. PMID- 8191037 TI - Transfer of gas from the acinus during continuous flow and intermittent positive pressure ventilation. AB - We used a technique of measuring Xenon133 washout (XeW) from the alveolar space to evaluate transfer of gas from the acinus (Mackenzie et al., J. Appl. Physiol. 68: 2013-2018, 1990) during 2 min of apnea, 2 min of tracheal insufflation with oxygen (TRIO) and 90 sec of intermittent positive pressure ventilation (IPPV) in 6 anesthetized and paralyzed dogs. Xenon133 dissolved in saline was injected into an occluded acinar region through a pulmonary artery catheter, and XeW was measured by gamma scintillation scanning. With this technique, XeW during apnea represents the contribution of cardiogenic oscillations in regional flow. The XeW rate constant (min-1 +/- SE) was 0.37 +/- 0.03 during apnea. This was not different (P > 0.05) with TRIO (0.29 +/- 0.04). With IPPV, the rate constant increased to 3.49 +/- 0.39, faster than with either apnea or TRIO (P < 0.001). We conclude that: (1) TRIO does not increase convective gas transfer from the acini compared to apnea; and (2) transfer of gas out of the acini due to cardiogenic oscillations is a very small portion of the total gas eliminated during IPPV. PMID- 8191038 TI - Capillary-fiber geometry in pectoralis muscles of one of the smallest bats. AB - We previously reported striking similarities in the structural capacity for O2 flux in the highly aerobic flight muscles of a hummingbird and bat despite their significant differences in capillary-fiber geometry and number, and fiber size. However, the bats of that study (Eptesicus fuscus, BW 15-16 g) were about 5 times larger than the hummingbirds (Selasphorus rufus; BW 3-4 g). In this study, we examined the flight muscle in a bat of approximately the same size as the hummingbird to determine whether features found in the big brown bat would be accentuated or if there would be additional similarities with the hummingbird. The pectoralis muscle of pipistrelle bats Pipistrellus hesperus (BW 3-5 g) was perfusion-fixed in situ, processed for electron microscopy and analyzed by morphometry. Fiber size (group mean +/- SE, 314 +/- 22 microns 2 at 2.1 microns sarcomere length) and capillary geometry (high degree of tortuosity and branching) were remarkably similar to those in pectoralis muscle of the big brown bat. Thus distances from capillaries to the center of the fibers were not reduced in pipistrelle flight muscle (as in hummingbird) nor was capillary tortuosity and branching further increased (compared with big brown bat). Capillary-fiber surface ratio at a given mitochondrial volume/microns length of fiber was high and similar to that in big brown bat and hummingbird, consistent with the idea that the size of the capillary-fiber interface plays an important role in providing the great O2 flux potential in these muscles. In addition, capillary fiber number at a given fiber mitochondrial volume per micron length of fiber was similar to that in other muscles including big brown bat and hummingbird flight muscle, bat hindlimb and rat M. soleus. This supports the notion of a close relationship between capillary number and mitochondrial volume on an individual fiber basis in aerobic muscles. PMID- 8191039 TI - Effects of potassium and lactic acid on ventilation in anaesthetized cats. AB - Intravenous infusions of lactic acid alone, KCl alone and both together were administered to anaesthetized, spontaneously breathing cats. Ventilation (VI), end-tidal PO2 (PETO2), end-tidal PCO2 (PETCO2), arterial blood pressure and heart rate were recorded continuously. [K+]a and pHa were monitored using intravascular ion selective catheter electrodes. The increase in VI during infusion of KCl and lactic acid together was greater than that observed during infusion of lactic acid alone. The increment in VI produced by the addition of an infusion of KCl to the lactic acid infusion was greater than the increment produced by the addition of KCl to a control infusion of normal saline. The reduction in PaCO2 which occurred when KCl was added to the lactic acid infusion was similar to that when KCl was infused with NaCl. Thus the inhibition of respiration secondary to reduced PaCO2 was similar in both circumstances. These results suggest that the combined respiratory stimulant effect of elevation of [K+]a and acute lactic acidosis is more than additive. PMID- 8191040 TI - Effect of continuous swallowing on respiration. AB - We examined the effect of continuous swallowing on breathing pattern and ventilation in 7 adult subjects. Repetitive swallowing was induced by oral infusion of water at a variable rate of 40, 60, 80 or 100 ml/min, while the subject breathed through the nose. The number of swallows increased from a mean of 5.2 (+/- 2.7 SD) swallows/min during the control period to 9.2 +/- 2.0 to 13.7 +/- 2.9 swallows/min during infusion of 40 and 100 ml/min, respectively. The duration of interruption of breathing was bolus volume-dependent, increasing from 0.55 +/- 0.09 sec with a mean bolus volume of 4.6 +/- 1.4 ml to 0.87 +/- 0.23 sec with a bolus volume of 8.1 +/- 1.9 ml. The majority of swallows (73 +/- 12%) interrupted breathing during inspiration. The mean tidal volume, inspiratory and expiratory times during swallowing periods were higher than those recorded during the control period, but the mean level of ventilation was not different from control, at all swallowing frequencies. Repetitive swallowing did not result in a single incidence of aspiration or coughing. We conclude that mechanisms integrating breathing and swallowing allow repetitive swallowing to occur without compromising ventilation, and that these mechanisms perfectly orchestrate between breathing and deglutition to prevent aspiration. PMID- 8191041 TI - Effects of hibernation on blood oxygen transport in the golden-mantled ground squirrel. AB - Isocapnic O2 equilibrium curves (O2EC) were generated for winter hibernating and summer active ground squirrels (Spermophilus lateralis) at 7 degrees and 37 degrees C using thin blood film techniques. Half-saturation PO2 at 7 degrees C and pHa 7.46 were 5.8 +/- 0.1 and 6.9 +/- 0.2 Torr for hibernating and summer squirrels, respectively; P50 values at 37 degrees C and pHa 7.49 were 15.3 +/- 0.1 and 18.1 +/- 0.5 Torr, respectively. This increased blood O2 affinity in the winter animal results, in part, from reductions of RBC organic phosphates. The molar ratio ([ATP] + [DPG])/[Hb4] decreased from 1.55 in summer squirrels to 0.91 in winter hibernators. O2EC shape and CO2 Bohr effect were similar for the two animal groups, but varied with blood temperature. At 7 degrees C, Hill plots were nonlinear; Hill's n increased from values of 2.2-2.4 below 40% S to 2.7-2.9 above 60% S. At 37 degrees C, Hill plots were reasonably linear (n = 2.5). CO2 Bohr slopes (delta log P50/delta pH) for hibernating and euthermic squirrels were 0.37 +/- 0.02 and -0.40 +/- 0.03 at 7 degrees C, respectively, and -0.62 +/- 0.04 and -0.60 +/- 0.02 at 37 degrees C, respectively. Blood O2 capacity was significantly greater (P < 0.001) in the hibernator; hematocrit (55%) and [Hb] (19.1 g/dl) exceeded the summer squirrel values by 20% and 25%, respectively. Estimated PvO2 values for summer and winter animals at 7 degrees C and pH 7.46 were 7.25 and 6.94 Torr, respectively. This suggests that the effect of increased Hb-O2 affinity on PvO2 is offset by increased circulating [Hb]. We conclude that seasonal changes in the O2 transport properties of squirrel blood do not contribute to the depression of aerobic metabolism during winter hibernation. PMID- 8191042 TI - Central chemoreceptor stimulus in the terrestrial, pulmonate snail, Helix aspersa. AB - We studied the effect of hypercapnic and fixed acid central chemoreceptor stimulation on the pneumostome in the pulmonate snail, Helix aspersa. We found that focal stimulation of the central chemoreceptor area of the pulmonate snail brain with hypercapnic solutions more effectively increased the pneumostomal area than did fixed acid stimulation at the same extracellular pH. Disrupting intracellular pH regulation by inhibiting Cl- transport, either pharmacologically (DIDS) or by ion substitution (Cl(-)-free perfusate), enhanced pneumostomal responses to CO2. While maintaining a constant perfusate pH, addition of NH4Cl to the perfusate resulted in pneumostomal closure; whereas removal of NH4Cl from the bath resulted in pneumostomal opening. In conclusion, the ventilatory response to CO2 in H. aspersa does not require Cl- transport or conductance. Furthermore, changing pHi alone is an adequate stimulus for the central chemoreceptors in the snail. PMID- 8191043 TI - Regional training-induced alterations in diaphragmatic oxidative and antioxidant enzymes. AB - We examined the relationship between the intensity and duration of exercise training and the up-regulation of diaphragmatic oxidative and antioxidant enzyme activities. Nine groups of rats exercised for 10 weeks (4 days/week). Groups of animals exercised at three intensities (low, moderate, and high); at each exercise intensity, a group of animals ran at one of three exercise durations (30, 60, and 90 min/day). Sedentary animals served as controls. Muscle oxidative capacity was assessed by citrate synthase (CS) activity while antioxidant capacity was evaluated by total superoxide dismutase (SOD) and total glutathione peroxidase (GPX) activities. All intensities and durations of exercise training promoted significant (P < 0.05) increases in costal diaphragmatic CS, SOD, and GPX activities. Increases in costal CS, SOD, and GPX activity were independent of the exercise intensity and duration. High and moderate intensity exercise of 90 min duration significantly elevated (P < 0.05) crural diaphragm CS activity. Further, high and moderate intensity exercise of durations > or = 60 min promoted significant (P < 0.05) increases in crural diaphragm SOD activities. Exercise did not influence (P > 0.05) crural diaphragm GPX activity. We conclude that the training threshold for up-regulation of oxidative and antioxidant enzyme activities differs between the costal and crural diaphragm. PMID- 8191044 TI - [Pathological changes of the pyramidal eminence in chronic suppurative otitis media]. AB - Temporal bones of patients with chronic suppurative otitis media were used for evaluation of possibility of penetration of the infection from the cavum tympani into the facial nerve via the pyramidal eminence. The infection can spread to the facial nerve in two ways: via the natural opening on the pyramidal eminence through which tendon of the musculus stapedius is passing, without bone lesions of the eminence and via the sites of bone destruction on the eminence. PMID- 8191045 TI - Tracheal reconstruction. AB - Between 1983 and 1990 the authors treated 193 patients with laryngo-tracheal stenoses of diverse etiology. In 119 cases the stenoses was in the trachea. In 36 the stenoses extended to the subglottic region and in 1 case the carina was involved. The surgical procedure used in the tracheal stenosis was resection of the stenotic segment followed by end to end anastomosis. In most cases up to 6 cm of trachea could be resected. Two patients required a silastic prosthesis because the length of the stenotic area, 9 and 11 cm. The patient with the carinal involvement was treated by the insertion of a long Montgomery T tube. When the lesion included the subglottic area a partial resection of the cricoid cartilage and the damaged trachea was used. Associated surgical procedures had to be performed in order to close tracheo-esophageal fistulas, 2 cases, fixation of one of the vocal cords, 9 cases. Tracheal stenoses were cured in 90% of the cases with one surgical procedure, when the stenoses extended to the subglottic region, the cure rate was only 88.6%. PMID- 8191046 TI - Iatrogenic diseases in the surgery of the ear. AB - We made a retrospective study of 419 cases, who had undergone otological surgery for different reasons. In 55 of them we judged, that the pathology, may have been due to the previous surgery carried out in different hospitals. The disease encountered may have been iatrogenic. We have proceeded analyse of the probable cause and to suggest some techniques for dealing with the problem. We have also suggested criteria for the surgery and for the prevention of this occurrence. PMID- 8191047 TI - Aneurysmal bone cyst of the upper maxilla. AB - Aneurysmal bone cyst is a nosologic entity of low frequency that appears with greater incidence in large bones. Its presence in the upper maxilla is very rare, even more so in a thirteen year old boy. The author presents the case of an aneurysmal bone cyst of the upper maxilla, together with its investigations and the surgical treatment practiced in 1987. A comment is added on the surgical technique he might adapt nowadays for approaching this type of tumors. PMID- 8191048 TI - Schwannoma of the nasal septum. Apropos of 2 cases. AB - We present two cases of schwannoma of the nasal septum. One of the patients has neurofibromatosis type 2; however, her main complaint was nasal obstruction. Schwannoma deriving from the septum is an extremely rare pathology, both in systemic neurofibromatosis type 2 and as a solitary lesion. There are no characteristic symptoms. Histopathologic examination may be inconclusive so that the definitive diagnosis requires immunohistochemic studies or electron microscopy. Differential diagnosis includes several neurogenic and mesenchymal tumors. CT scan and MRI studies are helpful in evaluating the origin, localization and extension of the lesion. Complete resection of the mass is usually curative, although patients with neurofibromatosis present a higher risk of local recurrence and malignant transformation. PMID- 8191049 TI - Lethal midline granuloma: a case of Ki-1 lymphoma. AB - Lethal midline granuloma syndrome (LMG) is the clinical term generally used to describe a rare clinical entity of unknown cause characterized by a progressive and often fatal ulceration and destruction of the upper airway involving the nose, the paranasal sinuses and the soft tissues of the face. The following histopathologic entities have always been grouped under the term LMG: Wegener granulomatosis (WG), non-Hodgkin lymphoma, polymorphic reticulosis (PR) and idiopathic midline destructive disease (IMDD). Today in order to begin an adequate therapy a differential diagnosis is necessary. The progresses in clinical immunology and immunohistochemistry and cytophotometric findings are useful to define the LMG syndrome better. First of all the LMG must be discriminated from localized WG occurring in the midface. Serologic examinations of patients with WG in its active form show a high percentage of autoantibodies against cytoplasmic structures in leucocytes and monocytes. Moreover a review of the literature allows us to suppose that cases described as IMDD and PR are indeed a large evolutionary spectrum from almost benign to fatal malignant lymphoma. We report a case of Ki 1-lymphoma presenting as LMG syndrome. PMID- 8191051 TI - Functional surgery of ceruminoma of the external and/or middle ear. AB - The paper describes two cases of "Ceruminoma" of the external and/or middle ear, treated by conservative surgery. The authors illustrate, besides morphological and histological features of ceruminoma, the surgical treatment modulated on the basis of an exact identification of the lesions. PMID- 8191050 TI - [Tumors of the ceruminous glands: revision of the literature and report of a case in the middle ear]. AB - The ceruminous glands tumors are very rare pathologies, being even rarer their origin other then the external auditory canal. In this paper, we report a case of ceruminous adenoma of the middle ear and study other 125 cases related in the literature since 1941. We analyze the incidence of each hystological type, the sex, race, age and site of origin of the tumors. PMID- 8191052 TI - [Surgical technique and results of cochlear implant in normal or ossified cochlea]. AB - The authors describe the surgical technique and results of the Nucleus device in 50 recipients. Cochlear ossification was present in one third of patients. Total insertion was possible in all cases with a partial ossification (< or = 8 mm), and once in a case with a total ossification (> 8 mm) of the scala tympani of the basal turn. Results were not significatively different in normal cochleas and in ossified cochleas. The authors describe a per-operative algorithm in front of a basal turn ossification, emphasizing on the insertion in scala vestibuli through the oval window. According to the results, the authors prefer the use of a multi channel cochlear implant than a monochannel implant, even in ossified cochleas. PMID- 8191053 TI - [Sudden deafness: a randomized comparative study of 2 administration modalities of hyperbaric oxygenotherapy combined with naftidrofuryl]. AB - Hyperbaric oxygen therapy is one of the numerous therapies which have been proposed in the management of sudden deafness. It is presumptuous to claim the efficiency of any treatment in a pathology where both the origin and the actual rate of spontaneous recovery are unknown. The grounds of therapies are therefore empirical but the need of urgent therapy is dictated by ethics. This study compares the effects of hyperbaric oxygen therapy in two groups of patients; according ot their order in randomization the subjects were treated either at a rate of 1 session or 2 sessions per day. Hyperbaric oxygen therapy was associated with infusion of Naftidrofuryl to counteract the vasoconstrictive effect of increased oxygen pressure in blood. Steroids were also administered simultaneously to avoid, for the same reasons, cerebral oedema. Normovolemic hemodilution (Dauman et al. 1983) was systemically performed in all the patients preliminarily to hyperbaric oxygen therapy, in order to reduce the haematocrit and thus facilitate blood supply. The efficiency and the side effects were similar in the two groups, provided that some principles in the selection and the monitoring of the patients were respected. The rate of 2 sessions of hyperbaric oxygen therapy per day has obvious advantages in view of health policy, but it requires the hospitalization of the patient and should be restricted to the younger subjects. PMID- 8191054 TI - [Hemorrhagic complications of lower turbinectomy]. AB - Concerning 52 inferior turbinectomies, the authors analyse the haemorrhagic complications of these surgical operations. They deplore 4% of serious haemorrhages. These ones may immediately occur during the surgical operation or in the next 15 days. No technique can prevent an haemorrhage. So that the patient must be notified of the risks he runs and the indications have to be seriously discussed. PMID- 8191055 TI - [Deafness after meningitis and cochlear implant in children]. AB - The authors have studied 70 postmeningitic hearing losses in children. The deafness was acquired before the age of 2 year-old in 71% of the cases. Profound losses were observed in 50% considering the 1000 Hz at +100 dB, on the best ear as a selection criterion, 31 cases/70 (= 44%) could benefit from a cochlear implant. Among these 31 cases, 71% (= 22 cases) are prelingually deafness, that is which have occurred before the age of 2 years old. In 2 profound deafness cases, a late improvement of initial threshold, brings to consider with caution the 6 to 12 months time limit which is recommended by the different teams. In 3 other cases of moderate or severe losses, an improvement of the thresholds has been also observed. Because of psychological disturbances or other after-effects, a very regular medical following of these children is needed. PMID- 8191056 TI - [Extensive cholesteatoma without intrapetrous involvement. Discussion on the surgical approach]. AB - Based on 8 observations, the authors analyze the extension of middle ear cholesteatomas on the anterior attic and the anterior supralabyrinthine cellular groove, the internal retrotympanum and the posterior sublabyrinthine cellular groove, the hypotympanum and the anterior sublabyrinthine groove, the retrolabyrinthine region and the translabyrinthine and posterior supralabyrinthine grooves. Despite progress in imaging and optical instrumentation, exact precision of the lesions sometimes remains impossible. The patient must be warned of a possible enlargement of the operative pathway and its consequences. PMID- 8191057 TI - Initial experience of peroperative electrocochleography monitoring in stapedectomy. AB - Clinical experience of intraoperative ECochG monitoring during stapes surgery is reported. Selected surgical phases have been taken into consideration, laying particular stress on the phase corresponding to the opening of the labyrinthine spaces. Compound action potential (CAP) amplitude and latency showed, a supposed, an inversely proportional relationship in most of the cases. Abnormal findings were also recorded in some patients, thus giving rise to different electrophysiological hypotheses. A proposal for an "in vivo" model for the study of the electrophysiological changes due to the opening of labyrinthine spaces is made. PMID- 8191058 TI - [Cleft palate and inflammatory diseases of the middle ear]. AB - Based on a series of 57 children who were operated for velar clefts, the authors studied the different associated aspects of middle ear inflammatory pathology: physiopathology, occurrence, evolution, complications. Seromucous otitis was initially found in 87% of the cases. Three years after surgery, it persisted in 70% of the cases. These children should be monitored on a long-term basis for timely detection of any and all evolution towards chronic otitis or even cholesteatomas. PMID- 8191059 TI - Structure of the reticular lamina and repair after noise injury. AB - Laser Scanning Confocal Microscopy (LSCM) and specific labeling techniques were employed to examine the distributing of F-actin and microtubules in the reticular lamina of the guinea pig and monkey organ of Corti. Actin specific label was found in the circumferential belt of adherens junction at the borders between cells in the reticular lamina, and in the cuticular plate of hair cells. The distribution of actin in the adherens junction belt was asymmetric. Actin label was not found in the fonticulus, where the microtubule organizing center resides. Actin free areas were also found between the junctional actin and the cuticular plate. Microtubule specific label was very intense in supporting cells. In normal hair cells, the spatial distribution of tubulin at the reticular lamina is mutually exclusive with that of actin. After noise exposure, a belt of actin was found in the central portion of degenerating outer hair cells, possibly representing a constricted circumferential junction. Expanded supporting cells replaced degenerating hair cells and maintained the confluence of the reticular lamina during the dynamic process of scar formation. A complex network of actin rich cables appeared at sites of degenerating inner hair cells, suggesting that more than two supporting cells are involved in scar formation for inner hair cells. LSCM proved an attractive method for analysis of the organ of Corti since preparation of the tissue is relatively rapid, preparation artefacts are minimized, different markers in the same specimen may be co-localized and out-of focus fluorescence blurring is eliminated. PMID- 8191060 TI - [Non invasive naso-sinusal aspergillosis. Contribution of endonasal microsurgery. Apropos of 16 cases]. AB - The authors report on 16 new cases of non-invasive nasosinusal aspergillar sinusitis over a period of 4 years. They stress the importance of the local inducive factors in such apparently healthy patients. The value of treatment by endonasal microsurgery is underlined, enabling the positive diagnosis and cure of these chronic sinusites that do not respond to medical treatment. PMID- 8191061 TI - [Spontaneous hemorrhage of the parathyroid disclosed by an extensive cervical hematoma]. AB - Extra capsular bleeding occupies a particular place within the evolutional complications of parathyroid tumors. Its rarity, the difficulty of the pre operative diagnosis and its potential evolution towards airway obstruction by compression underline its singular character. A case is presented where an evolutive cervico-thoracic hematoma, evolving without functional symptoms, has led to the diagnosis of parathyroid hyperplasia. The diagnostic and therapeutic characteristics of this pathology are detailed and confronted to the similar cases found in the literature. PMID- 8191062 TI - [Castelman disease. Apropos of 2 cervical localizations]. AB - The authors report two cases of neck localisations of Castelman's disease. A cervical mass and an inflammatory syndrome are the main clinical and biological symptoms. The diagnosis of the disease is based on histology. Surgery provides a complete recovery. PMID- 8191063 TI - [Surgical treatment of proboscis lateralis: apropos of a case]. AB - A case of proboscis lateralis with complete absence of the left half of the nose, replaced by a lateral trunk, is reported. A surgical correction was required. On a first-stage, the length of the mucocutaneous cylinder was sutured to the half nose to perform a functional, well situated nostril. One or a few operations will take place, later, to put the final touches in the nose. They must respect the compromise between the maximal growth of the tissues and the least psychological trauma for the child. PMID- 8191065 TI - [Transoral approaches to the skull base. An attempt of systematization]. AB - This is a technical note concerning the classifications of the various operations possible via the buccal route towards the base of the skull and the first vertebrae. A part from the Hardy vestibulo-septal approach, mention must be made of the buccal and transpalatine approach, the direct buccal approach, the buccal approach widened downwards by transmandibular osteotomy, and finally the transmandibular and transcervical approach. These different technique enable the ablation of extradural and even intradural lesions at the level of the clivus, but are limited on the side by the pterygoid process and the large vessels. PMID- 8191064 TI - [Nasosinusal inverted papilloma. Apropos of 6 cases]. AB - We report in this study six cases of the inverted papillomas of the nose, that we have noticed in the ORL's department in 20 august hospital from 87 to february 1992. It's about patients aged from 12 to 60 years old, a child, a woman and four tabagic men, one of who has an allergic rhinitis. The clinical symptomatology is evocative of our patients and is especially marked by the unilateral nasal obstruction. The radiology which has an important resort permitted to lean the diagnosis and to precise the extension of the tumor. The anatomopathologic examination permittedus confirm the diagnosis with certitude. The surgical treatment is chosen for the whole of our patients. The evolution in all the cases is satisfying. We neither notice a recurrence nor a malignant transformation. PMID- 8191066 TI - [Widened retrolabyrinthine approach: application to the surgery of acoustic neuroma]. AB - For a long time, the role of the widened retrolabyrinthine approach (WRLA) in surgery of the posterior fossa was restricted to functional surgery of the erebellopontine angle (CPA). The widening technique described makes it possible to adapt it to surgery for the exeresis of APC tumors, irrespective of their histological nature. We have used this approach to treat 19 neurinomas of the VIII and 11 other lesions. The results obtained in the preservation of facial function and hearing match those recorded with more traditional approaches, such as the translabyrinthine and suboccipital retrosigmoid approaches. By its modularity in the access space, it is the multi-purpose approach for the CPA. In our therapeutic armamentorium, given its possibilities to preserve hearing, it has taken the place of the less flexible and more dangerous suboccipital approach. PMID- 8191067 TI - [Mechanical sutures in ORL cancers, value, indications, techniques and results apropos of 30 cases]. AB - The authors report their experience in closure of the pharynx following total laryngectomy or total pharyngolaryngectomy by mean of the TA 55 instrument. The technique is described stressing the particular point of good presentation of the mucosa and the importance of the crossing of the lines of staples when two clips are used. An analysis of 30 cases studies is presented with the results as of the date of removal of the nasogastric catheter and the percentage of fistula. This technique appears to be rapid, safer than conventional methods of closure and less complications have been encountered in this series. PMID- 8191068 TI - [Transfrontonasal approach: development of a mixed approach to ethmoid tumors. Experience of 12 cases]. AB - Our experience in approaching ethmoid tumors through a combined pathway is currently based on 81 patients. 69 of them were malignant tumors treated by the neurosurgical subfrontal and paralateronasal transfacial rhinological approach. For the past two years, we have adopted the technical modification described in Bordeaux by Pinsolle and San-Galli enabling the approach of the ethmoid bone by means of a unique (Unterberger's scalp) incision and a unical frontonasal flap. 12 patients benefitted from this transfrontofacial access. The advantages and disadvantages of the technique are discussed. PMID- 8191069 TI - [Seromucous otitis. Treatment and long-term development]. AB - The course of otitis media with effusion was analysed on two groups of children, the first one of 133 serous otitis found at the same time as other troubles, the second one of 127 children all treated by tympanotomy tubes, in association with other treatments. In the first group, the cure rate is just better than one half. A normal control one month after surgery has some prognostical value, this results remaining in 3 cases on four. The great size of removed adenoids has prognostical value too, further surgeries for transtympanic tubes being less frequent. In the second group, we can see likely good mean or long term result of tympanic tubes, most of the complications happening on cleft palate cases. The various treatments: adenoidectomy, antibiotics, steroids, thermalism, eustachian tube physiotherapy, mucolytics, decongestants and anti-histaminics are discussed in regard to recent studies. PMID- 8191070 TI - [Cervicofacial SMAS and its relations with intrapetrous facial nerve]. PMID- 8191072 TI - [Pneumopathy caused by amiodarone in internal medicine: 8 cases]. AB - We report on eight cases of amiodarone pulmonary toxicity. Main clinical symptoms are acute/subacute dyspnea or progression in some cases. Amiodarone responsibility is difficult to ascertain. Several arguments can be presented: clinical symptoms with dyspnea and/or fever and/or cough, interstitial or in diffusing capacity for carbon monoxide, abnormal broncho-alveolar lavage cytopreparation smear with increased percentage of lymphocytes and polymorphonuclear leucocytes in typical cases; trans-bronchoscopic lung biopsy failed to provided information on amiodarone toxicity in the two patients where biopsy were performed. Differential diagnosis is an essential step to eliminate other possible causes ie pulmonary micro-organism infections, cancer or pulmonary oedema secondary to heart failure. In one case acute pulmonary toxicity occurred early, after introduction of amiodarone, with a proposed immuno-allergic mechanism. In other cases, chronic amiodarone deposition in the lungs can explain clinico-radiologic features. In six cases improvement was observed after discontinuation of therapy within a 6-months period. PMID- 8191071 TI - [The role of adrenal gland x-ray computed tomography and scintigraphy using radiolabelled norcholesterol in the etiological diagnosis of primary hyperaldosteronism]. AB - The major etiologies of primary aldosteronism are aldosterone-producing adrenal adenoma, requiring a surgical treatment, and bilateral hyperplasia, usually managed with medical therapy. We only report a retrospective study on 22 patients with primary aldosteronism diagnosed by clinical and usual biochemical tests. All the patients were explored by computed tomography scan (CT) and iodomethyl norcholesterol scintigraphy. The purpose of this study was to compare the capacity of the two methods to differentiate adrenal adenoma and hyperplasia. The CT scan was more sensitive (sensitivity: 88%) compare to scintigraphy (sensitivity: 64%) for the diagnosis of adrenal adenoma. However, the scintigraphy was a useful tool to detect asymmetric macronodular adrenal hyperplasia. Therefore, the catheterisation of adrenal venous would be only necessary for a few cases. We conclude from this study and the literature review that CT scan and iodomethyl-norcholesterol scintigraphy are complementary and both useful to increase diagnostic reliability of primary aldosteronism. PMID- 8191073 TI - [Monoclonal antibodies and rheumatoid polyarthritis]. AB - Monoclonal antibodies allow to foresee selective immunotherapy in rheumatoid arthritis (RA). Several molecules implicated in the immunopathogenesis of the disease represent the targets (antigens) of monoclonal antibodies already used in man: T cell antigens, T cell activation antigens, adhesion molecules, cytokines. The first open studies gave promising results. However complementary investigations are requested to confirm the clinical efficacy and to precise the real place of these biologic agents in the strategy of treatment of RA or auto immune diseases. PMID- 8191074 TI - [Tuberculosis and HIV]. AB - With the increased number of HIV infected patients, tuberculosis has become more frequent in Europe, USA and particularly in Africa. Impaired immunity, poor life conditions and high prevalence of tuberculosis in the general population facilitate the transmission of the disease. Tuberculosis is often seen early in the course of HIV infection and sometimes reveals the underlying immunodeficiency. Most of these cases are due to reactivation of earlier primo infection when tuberculosis occurs later in the HIV disease, it may be secondary to a recent contagion. The infection may be localized in the lungs or in extrathoracic sites such as lymph nodes, liver, spleen, blood or meninges. The diagnosis is based on direct visualization of acid fast bacilli in gastric aspirate or BAL, on positive blood cultures or in histological findings which often show atypical granulomatous reaction without marked caseation. The role of the intracutaneous tuberculin test remain questionable as it often proves negative. A positive skin reaction can be useful for the diagnosis of tuberculosis, however, this is rarely observed. An early diagnosis is important in order to improve the prognosis and this justifies the frequent instauration of empiric treatment. The usual quadritherapy is efficacious and when started early permits in most cases a favorable outcome. The duration of treatment is poorly standardized but approaches 9-12 months in most instances. The drugs are not always well tolerated. A life-long maintenance therapy seems to have become necessary and primary prophylaxis might be of interest. The increased occurrence of drug resistant stains adds to the interest of preventing transmission, particularly in the hospital. PMID- 8191075 TI - [Lyme disease disclosed by disabling amyotrophy]. AB - The Lyme disease, which was first found in Lyme, USA, in 1975 is an infectious multi-system disorder whose agent, the Borrelia Burgdorferi, was identified in 1983. Various disease manifestations have been reported since them. We report a case of Lyme disease manifestation in the muscle revealed by serious amyotrophy in the scapular muscles, in the neck and in the trunk with scapula alata accompanied by noctural lumbago which is resistant to non steroid anti inflammatory drugs. Electromyography showed patterns of the myogenic type in the serrate anterior and infraspinous muscles on both sides and patterns of the neurogenic peripheral type in the lower extremities. The histological, immunohistochemical and electron-microscopal studies of the muscle biopsy have been without any pathological result. Creatine kinase and aldolase proved normal. Serological antibodies were not significantly increased. A positive diagnosis was obtained by lumbar puncture which showed lymphocytic meningitis, by demonstrating specific antibodies in the cerebrospinal fluid and by Western Blot antibodies analysis. Efficacy of the antibiotic therapy has resulted in a rapid regression of the symptoms, which is a further confirmation of the previous diagnosis. PMID- 8191076 TI - [Acquired corticotropin insufficiency in adults. 2 new cases]. AB - We report two new cases of isolated corticotropin deficiency, associated with TSH deficiency in one of the two patient. The diagnostic was made difficult because the symptoms were mainly psychiatric. Low plasmatic cortisol and ACTH level were found, with low T3, T4 and TSH in the second patient. The TSH did not respond to the stimulation by TRH. The cerebral tomodensitometry and magnetic resonance imaging focused on the sella turcica were normal, eliminated a tumor and showed an empty sella turcica. The patients have to be followed-up because an isolated deficiency may further complete to panhypopituitarism. PMID- 8191077 TI - [Staphylococcus aureus endocarditis: an unusual clinical picture]. AB - We describe an unusual presentation of bacterial endocarditis due to Staphylococcus aureus in a 50 year-old woman with mitral insufficiency. The disease began by a vascular purpura without fever and a digital embolism. The source of infection was anal ulcerations. Diagnosis of endocarditis was made possible by trans-oesophagus echocardiography but not by trans-thoracic echocardiography. The patient was successfully treated by surgery associated with antibiotherapy. This observation emphasizes the indications of surgery at the acute phase of endocarditis. The anal source of endocarditis is original, no other case has been found in the literature. PMID- 8191078 TI - [Severe and resistant cutaneous involvement in dermatomyositis: value of intravenous immunoglobulins]. PMID- 8191079 TI - [An unusual cause of digestive hemorrhage: gastric botryomycosis]. PMID- 8191080 TI - [Biological changes in malarial attack]. PMID- 8191081 TI - [Malignant adrenocortical carcinoma and ketoconazole]. PMID- 8191082 TI - [A new case of serofibrinous pleurisy in RS3 PE syndrome]. PMID- 8191083 TI - [Value of renal biopsy by the transjugular approach in the diagnosis of renal sarcoidosis]. PMID- 8191084 TI - [Tricuspid valve endocarditis caused by Staphylococcus epidermidis albus in a cirrhotic patient]. PMID- 8191085 TI - [Acute polyarthritis, pulmonary fibrosis and Raynaud's phenomenon disclosing polymyositis with anti-JO-1 antibody associated with Gougerot-Sjogren syndrome]. PMID- 8191086 TI - [Pleural tuberculosis in hairy cell leukemia treated with interferon]. PMID- 8191087 TI - [Hepatitis E]. PMID- 8191088 TI - [Assay of free thyroxine by immunoenzyme method in general diseases]. AB - In non thyroid illnesses the degree of serum FT4 levels perturbation may be variable according to the assay used. The performance of a new FT4 immunoenzymatic assay (Enzymmum test, BMF) was evaluated in 78 euthyroid controls and in 99 sick patients with renal insufficiency, severe diabetes, hypoalbuminemia, severe general disease or under heparinate treatment. Results were compared to two RIA assays: by immunoextraction (CA2), known to be little disturbed by hypoalbuminemia and considered as a reference method, and by a labelled antibody (MAB, Amerlex) easier to use. In controls mean values and T4 L confidence intervalls were comparable with the three assays. In patients FT4 levels were diminished in case of renal insufficiency but the mean values obtained by BMF and CA2 did not differ. FT4 levels of heparinate treated patients were elevated with BMF and CA2. Generally patients are better classified as euthyroid with the CA2 assay (5.6% misclassification) than with BMF (11.2%) or MAB (12.4%), particularly in case of serious disease. A good linear correlation was found between the three methods. With the new BMF assay results were grossly comparable to those obtained by other assays. However the determination of FT4 levels alone appeared no sufficient to characterize the patients thyroid status. PMID- 8191089 TI - [Lupus in children in Tunisia]. AB - In this study, we have analyzed the clinical and serological features related to 16 Tunisian children in whom diagnosis of systemic lupus erythematosus was made before or at the age of 15. Renal involvement was found in 75% of cases and renal biopsies have mostly revealed severe histologic patterns. All of the patients who have been followed received corticosteroids and in some cases required additional cytotoxic drugs in order to control disease activity. Five children died in a context of a renal failure. This study of childhood lupus in Tunisia confirms that the clinical course of this disease in children is often aggressive. PMID- 8191090 TI - [Chronic urticaria-macroglobulinemia (Schnitzler syndrome): developing to IgM myeloma. Apropos of a case]. AB - Schnitzler's syndrome has been described in 1972. It associates a chronic urticaria with leukocytoclastic vasculitis, a macroglobulinemia, bone pains, hyperostosis. In the twenty three cases reported, the evolution is benign but three patients including the princeps case developed a Waldenstrom's disease or a lymphoplasmocytic lymphoma. We present the case of one patient, aged 65, with Schnitzler's syndrome, who, after 6 years evolution, presents a IgM myeloma. Schnitzler's syndrome appeared as a pre-hemopathic state which has to be taken care of regularly and for a long time. PMID- 8191091 TI - [Isolated zinc deficiency and necrolytic migratory erythema. Apropos of a case]. AB - The case of 87-old year woman with necrolytic migratory erythematosus rash without elevated plasma enteroglucagon is discribed. Decreased serum zinc level, response to oral zinc substitution and follow up proved the zinc deficiency. PMID- 8191092 TI - [Encephalopathy and memory disorders during treatments with mefloquine]. AB - Benign psychiatric side effects have been frequently associated with mefloquine therapy. On the other hand, severe psychiatric disorders due to mefloquine are rare but must be detected by physicians. Two such cases are reported. In the first case, excessive curative mefloquine therapy caused an acute psychotic state which ultimately regress without treatment. The second report concerns a transient memory failure following prophylactic mefloquine treatment. The causative role of this compound is being discussed and the importance of a differential diagnosis of neuropsychiatric disorders from toxic or parasitic origin is underlined. Circumstances aggravating such neuropsychiatric side effects and actual recommendations concerning the prescription of mefloquine are recalled. PMID- 8191093 TI - [End-stage chronic renal failure in myeloma: results of dialysis]. AB - Nowadays, maintenance dialysis can be proposed to patients suffering from myeloma with end-stage chronic renal failure. We report here data from eight patients dialysed either by hemo- (6) or peritoneal dialysis (2), together with chemotherapy in half of them. Six patients died; the longest survival has been about 6 years. The main cause of morbidity was sepsis, especially in peritoneal dialysis patients; therefore we now favour hemodialysis in patients exposed to aggressive chemotherapy. We think dialysis justified in all cases, including those with high tumor mass, in order to expect the effect of chemotherapy; then, provided good response to drugs, further survival can be consistently improved. Once on maintenance dialysis, main drawbacks for these patients are cardiovascular complications (AL amyloidosis) and above all anemia; the latter however can be markedly improved, thanks to erythropoietin therapy which provides these patients with much better quality of life. PMID- 8191094 TI - [What criteria for the diagnosis of antiphospholipid syndrome?]. AB - The "historical" definition of the antiphospholipid syndrome is the most widely used: history of at least one venous and/or arterial thrombosis and/or two miscarriages, and positive tests for lupus anticoagulant and/or anticardiolipin antibodies, on two occasions more than 8 weeks apart. More recently, a Mexican group proposed another definition taking into account the number of clinical manifestations and the titer of anticardiolipin antibodies to categorize patients as definite, probable or doubtful antiphospholipid syndrome. The respective merits and limitations of both definitions are discussed. PMID- 8191095 TI - [Angina with healthy coronary vessels and scleroderma]. PMID- 8191096 TI - [Biological diagnosis of leptospirosis by PCR (polymerase chain reaction)]. PMID- 8191097 TI - [Asymptomatic hypoglycemia caused by cibenzoline]. PMID- 8191098 TI - [Uncommon dysphagia caused by ectasia of the left atrium in atrial septal defect]. PMID- 8191099 TI - [Toxicity of levamisole in adjuvant chemotherapy for colorectal cancer]. AB - We studied the levamisole toxic effects in adjuvant therapy for colorectal cancer. The therapy toxic effects on 127 patients were statistically more important in the levamisole-treated group compared to patients treated with folinic acid and 5-fluorouracil alone. Randomized studies in progress will demonstrate the real therapeutic value of levamisole. PMID- 8191100 TI - [Hospitalization in internal medicine of nonagenarians. Study of 150 cases]. AB - Very elderly patients represent an increasing rate of hospitalized patients in internal medicine unit. Their admission and discharge modes, their morbidity and explaining factors for length of stay are still bad knowned. This prospective study concerns 150 patients stays, over 90, in an internal medicine and geriatric unit. Morbidity is mainly related with a high number of diagnoses (3.4 +/- 1.5). Most of them (2.8 +/- 1.3) are relevant for the hospitalization. The major categories of observed diseases are degenerative dementia, arrhythmias and adverse drug reactions. The main hospitalization mode is the non programmated one. We noted a high rate of death during hospitalization (17%). The main discharge mode is return home (88%). The length of stay among the survivals is significantly correlated (P < .001) with the number of diagnoses, the need for institutionalization and the sex. This pattern explains more than 20% of the variance of the length of stay. The data confirm the specificity of the medical care of very elderly patients. They also suggest that the french model of medicalization of the information system must be adapted to increase its pertinency among very elderly. PMID- 8191101 TI - [Increase of aminotransferases]. AB - Elevated aminotransferases activities are frequent in medical practice. In acute elevations, the mains causes are generally easily found (viral, drug-induced, toxic, ischemic). In moderate or prolonged elevations, the most frequent causes are steatosis (alcoholic, diabetes, obesity) and chronic hepatitis (viral B, D, C, drug-induced and auto-immune diseases. PMID- 8191102 TI - [Peripheral neuropathies and hemopathies]. AB - In our experience, the incidence of an association between peripheral neuropathy and hemopathy is around 7%. The corresponding nerve involvement may reveal or complicate a known hemopathy. The exact cause-effect relationship is not always easy to identify. We discuss here the peripheral nerve complications of acute leukemia, myeloproliferative disorders, monoclonal dysglobulinemia, non-Hodgkin's malignant lymphoma and Hodgkin's disease. The peripheral neuropathy arising in cases of monoclonal dysglobulinemia, non-Hodgkin's malignant lymphoma have most benefited from ultrastructural examination and advances in immunological and immunocytochemical techniques. Accurate determination of the lesional mechanism should help devise appropriate therapeutic strategies. PMID- 8191103 TI - [Coxiella burnetii endocarditis on a bioprosthetic valve: review of the literature apropos of a case]. AB - A 51-year-old woman, originating from Algeria, developed Q fever endocarditis on porcine bioprosthetic mitral valve. She had chronic course with nonspecific symptoms, such as dyspnea and fever, hepatosplenomegaly, and developed progressive cardiac failure. Worsening of hemodynamic state led to prosthetic valve replacement. Hemocultures were all negative, and the diagnosis of Q fever was unexpectedly performed by systematic screening for specific serum antibody to Coxiella burnetti. High phase I and II specific IgG and IgA antibody titers against C burnetii were found. The patient was treated by doxycycline and ofloxacin, and improved rapidly. Prosthetic valve constitutes likely predisposing factor for the development of chronic Q fever endocarditis. This observation emphasizes the need to search for Q fever in prosthetic valve dysfunction, in particular when hemocultures are negative. PMID- 8191104 TI - [Disclosure of systemic lupus erythematosus in a case of hepatitis caused by ibuprofen]. AB - We report the case of an hepatitis induced by ibuprofen in a young 32 years old woman, which allowed to discover an until then unknown systemic lupus erythematosus. After an analysis of the data of the literature, we are able to estimate at more than a 50% the specificity of the above mentioned induced effect of this drug for the diagnosis of lupus. Thus, non only a meningitis, but also an hepatitis induced by the ibuprofen need a systematic research of a connective tissue disease. PMID- 8191105 TI - [Meningoencephalitis disclosing Behcet disease. Value of nuclear magnetic resonance imaging]. AB - A meningoencephalitis Behcet's disease revealing is reported. Magnetic resonance imaging is more sensitive than computerized tomography in detecting encephalitic lesions. However, no specific pattern may be retained. This exploration is non invasive and can be used to monitor the evolution after treatment. PMID- 8191107 TI - [Infectious endocarditis, risk factors, prevention. Research group for infectious endocarditis and jury of the consensus conference]. AB - Infective endocarditis, resulting from deposition of circulating microorganisms during a period of bacteremia on damaged endothelial heart valves, remains a serious disease. Its overall incidence did not decline in recent years, 24 cases/year/million inhabitants, in France. This can be explained by a modification of the type of underlying cardiac conditions with regression of rheumatic fever and increase of degenerative heart diseases, prosthetic valves and mitral valve prolapse. The risk of bacterial seeding on a damaged valve remains difficult to evaluate, the highest risk being for patients with prosthetic valve, previous infective endocarditis and cyanotic congenital heart disease. A case-control study, done in 1991, confirmed that procedures are risk factors for infective endocarditis and that the multiplicity of procedures increases the risk. A French consensus conference on the prophylaxis of infective endocarditis has updated the recommendations for antibiotic prophylaxis. Two groups of cardiac patients were identified, based on the incidence and the severity of endocarditis occurring in patients with these conditions, 1) patients considered at risk which require specific prophylaxis, and 2) patients considered non at risk which do not require antibiotic prophylaxis. Procedures which require antibiotic prophylaxis are dental procedures and specific gastrointestinal and urologic procedures. As complex protocols are associated with poor compliance by practitioners and patients, the jury has aimed for simplicity and feasibility. PMID- 8191106 TI - [Hypothyroid hypertrophic myopathy in adults related to chronic lymphocytic thyroiditis. A case]. AB - The authors report a case of hypothyroid hypertrophic myopathy which reveal chronic lymphocytic thyroiditis. This entity est uncommon, can be the most important sign of hypothyroidism and cure after the institution of thyroid hormone replacement therapy. The E. M. G. is usually myopathic and serum muscle markers (myoglobin and enzymes) increased. Pathologic studies of muscle show caracteritic but non specific and inconstant abnormalities. Hypothyroid myopathy could be caused by a mitochondrial oxidative phosphorylation deficiency or changes in muscle contractile properties (both in fibre type proportion and in the properties of the muscle contractile proteins). PMID- 8191108 TI - [Preventive drug therapy of postmenopausal osteoporosis]. AB - Osteoporosis, one of the most important disorders associated with aging, needs active prevention. Estrogen therapy prevents the early phase of bone loss and decreases the incidence of subsequent osteoporosis related fractures. All estrogens are probably not equally effective against post menopausal bone loss. In USA conjugated equine estrogens are the most used. In Europe estrogen therapy is usually applied with 17 beta estradiol with different ways of administration. If estrogen therapy cannot be used, there are limited datas about the use of bisphosphonates or calcitonins in the prevention of post menopausal bone loss, but not still any data about the subsequent incidence of fractures. In all cases, calcium supplementation is effective. PMID- 8191109 TI - [Retroperitoneal teratoma as "first symptom"]. PMID- 8191110 TI - [Dermatopolymyositis and chronic lymphoid leukemia. Apropos of 2 cases]. PMID- 8191111 TI - [Iron deficiency anemia disclosing celiac disease in adults]. PMID- 8191112 TI - [Experimental evidence that endogenous TSH modulates microsomal antigen expression: clinical implications]. AB - The purpose of this work was to study if TSH has a role in TPO antigen expression in vivo. Using the cytotoxicity assay we measured TPO expression and correlated it with TSH serum levels in 3 groups of rats: control, hypothyroid and hypothyroid supplemented with thyroxine. For comparative purposes, in the cytotoxicity assay we used rat monoclonal antiTPO or human sera with high titles for antiTPO antibodies. Hypothyroid rats showed marked elevations of TSH serum levels and TPO antigen expression in their thyrocytes when compared to the control and supplemented group. A positive correlation between TPO antigen and TSH levels was observed (r = 0.69, p < 0.001). There was an excellent correlation between TPO results using rat monoclonal or human sera antibodies (r = 0.94 p < 0.0001). It is concluded that TSH modulates TPO antigen expression. These data are of clinical relevance considering that TSH modulates the expression of other antigens that can maintain the immune response and perpetuate the immune disease in patients with Graves disease treated with antithyroid drugs. Thus, the avoidance of TSH hypersecretion with administration of thyroxine could be useful to treat these patients. PMID- 8191113 TI - [Nucleolar organizer regions in uterine cervical cancer and its precursor epithelial lesions]. AB - The number of nucleolar organizer regions was assessed in 115 histological samples of uterine cervical carcinoma or precursor epithelial lesions. Normal endocervical or exocervical epithelial tissues were used as controls. Nucleolar organizer regions were stained with colloidal silver in formalin fixed histological samples and quantified in 100 cells, according to Crocker's method. The mean number of nucleolar organizer regions were 13.7 in infiltrative carcinoma, 9.15 in carcinoma in situ, 9.3 in severe dysplasia, 8.4 in moderate dysplasia, 7.5 in mild dysplasia, 6.4 in condylomas and 3.2 and 2.9 in normal exocervical and endocervical epithelia respectively. There were significant differences in the number of nucleolar organizer regions between normal and abnormal tissues and between the different lesions except between moderate and mild dysplasia and between carcinoma in situ and moderate and severe dysplasia. The highest number of nucleolar organizer lesions was always observed in the basal strata of both normal and abnormal tissues. It is concluded that nucleolar organizer regions are a good index of cellular proliferation in uterine epidermoid cervical carcinoma and its precursor lesions, and have a diagnostic value in infiltrative carcinoma. PMID- 8191114 TI - [Effect of cholelithiasis and cholecystectomy on duodenogastric biliary reflux]. AB - The aim of this work was to study the influence of cholelithiasis and cholecystectomy on duodenogastric biliary reflux. Total bile acid concentration (TBAC) in fasting gastric juice was measured in 23 consecutive patients with cholelithiasis and functioning gallbladder before and at least 3 months after cholecystectomy (group 1) and in 14 healthy volunteers (group II). In group two, TBAC was 8.5 +/- 2.8 uMol/l (mean +/- sem), the preoperative value in group I was 32.8 +/- 8.9 uMol/l and the postoperative value 69.9 +/- 14 uMol/l (p < 0.002 compared with group II and < 0.035 compared with preoperative values). These results suggest that cholelithiasis, even with a functioning gallbladder is associated with a significant increase in bile reflux to the stomach, with raises further after cholecystectomy. PMID- 8191115 TI - [Seroprevalence of Legionella pneumophila infection in healthy, adults from Santiago, Chile]. AB - In order to investigate the L pneumophila seroprevalence in healthy adult population of Santiago, Chile, a serologic survey of antibodies to serogroups 1 through G was performed. Sera of 100 blood donors were studied with the indirect fluorescent antibody method. Positive results (> or = 1.64) were obtained in five samples. Titres > or = 1:128 were not observed. We conclude that the seroprevalence of L pneumophila in Santiago is 5% and that a single titre > or = 1:256 suggests the diagnosis of legionellosis. The low seroprevalence in Santiago is in agreement with the few cases of legionellosis reported. PMID- 8191116 TI - [Comparative in vitro activity of new oral macrolides against Streptococcus pyogenes strains]. AB - Some recently introduced macrolides have several clinical advantages over erythromycin. Azithrommcin, a prototype of these new macrolides could be a good alternative for the treatment of streptococcal pharyngitis, even over penicillin, whose failure rate can be as high as 30%. The aim of this study was to evaluate the in vitro susceptibility of 120 strains of S pyogenes isolated between 1990 and 1992 (40 per year), from diverse infections (specially tonsillitis). We determined Minimal Inhibitory Concentrations (MIC) of azithromycin, clarithromycin, roxithromycin, erythromycin and penicillin using the agar dilution method and the Minimal Bactericidal Concentration (MBC) by tube dilution for azythromycin and erythromycin. The MIC 90 for the new macrolides ranged from 0.03 to 0.12 microgram/ml, and was 0.03 microgram/ml for erythromycin and penicillin (not different). All strains were susceptible to all antibiotics and the date of isolation did not influence susceptibility. The MBC for azithromycin was 0.12 microgram/ml (identical to its MIC), which demonstrates the bactericidal effect of this antibiotic. It is concluded that this in vitro data supports the potential role of these new macrolides in the treatment of streptococcal infections. PMID- 8191117 TI - [Non-insulin-dependent diabetics with secondary failure: insulin therapy at bedtime combined with glibenclamide]. AB - Secondary failure and the requirement is common in patients with non-insulin dependent diabetes mellitus. The combination of sulfonylureas with NPH insulin at bedtime has been proposed to avoid high doses of insulin. We treated 18 patients (2 men, age range 47-76 yr) non respondent to diet and glibenclamide, combining NPH insulin in an average dose of 0.3 +/- 0.03 U/kg BW at bedtime for 6 months. Fasting serum glucose improved from 256 +/- 11 to 132 +/- 6 mg/dl and HbA1C from 13.6 +/- 0.4 to 9.9 +/- 0.2%. Four patients achieved a good control (defined as a HbA1C < 9), 9 a fair control (HbA1C 9.1-10) and 5 persisted with a bad control (HbA1C > 10). Well controlled patients were younger, had a shorter duration of diabetes and had a non significantly higher body mass index. Fasting serum insulin and C peptide levels achieved after glucagon injection were not predictors of the metabolic response to combined therapy. Tolerance to treatment was good, without changes in blood pressure or serum lipids and with a low incidence of hypoglycemia. There was a mean increase of 3.6 kg in body weight. After 6 months of therapy, maximum achieved C peptide values after glucagon increased from 3.3 +/- 0.3 to 4.5 +/- 0.4 ng/ml. It is concluded that combined glibenclamide and NPH insulin at bedtime is useful to treat secondary failure in non-insulin dependent diabetic patients, but their response in variable and non dependent on their beta insular secretion. PMID- 8191119 TI - [Blood pool in the study of hepatic hemangioma]. AB - Blood pool scintigraphy is a useful tool in the diagnosis of hepatic hemangioma. We reviewed retrospectively the clinical histories of 24 patients with abnormal blood pool scintigraphies and a presumptive diagnosis of hepatic hemangioma, based on clinical or ultrasonographic findings. In 20 of these patients, blood pool scintigraphy was diagnostic for hepatic hemangioma. The diagnosis was confirmed by an asymptomatic clinical evolution of 12 to 78 months in all the patients, CT scan in 8, angiography in 5 and liver biopsy in one. In the remaining 4 patients scintigraphy ruled out the presence of a hepatic hemangioma. Our results are similar to previous reports in the literature and blood pool scintigraphy has a high specificity for the diagnosis of hepatic hemangioma. PMID- 8191118 TI - [Colorectal cancer. Study of survival and surgical results]. AB - The aim of this study was to assess the progress in the surgical treatment of colorectal carcinoma in a 15 years period at the Catholic University Clinical Hospital. The medical records of 397 patients were retrospectively analyzed. Two hundred eighty four patients (164 male) aged 24 to 90 years old, subjected to elective and curative interventions, were selected for the study and separated in two groups: 132 subjects operated between 1975 and 1984 (group A) and 152 operated between 1985 and 1989 (group B). Group B patients were older (66.7 vs 61.3 years old), had a higher proportion of Dukes A tumors (11 vs 18%) and a lower proportion of lesions localized in the rectum (37 vs 49%). Rectal operations had higher morbidity than colonic interventions (35 vs 17.5%). Operative mortality was 0.7% in group A and 0.6% in group B. Ninety one percent of patients had a mean follow up of 38 months. Five years actuarial survival was 52% in group A and 69% in group B and 58, 74 and 46% for tumors Dukes A, B and C respectively. PMID- 8191120 TI - [Clinical correlations and evoked potentials in 29 cases of definitive multiple sclerosis]. AB - Aiming to correlate the alterations in evoked potentials with the initial clinical manifestations of multiple sclerosis, 29 patients with the disease were studied and 19 were followed for a lapse ranging from 1 to 11 years. Visual evoked potentials were studied in all the patients and 51% were abnormal. Auditory evoked potentials were assessed in 26 patients and 26% were abnormal. Somatosensory evoked potentials were made in 21 patients and 61% were abnormal. We found no relationship between clinical status and abnormalities in evoked potentials. In the followed patients, those with the worst clinical deterioration, initially had cerebellar symptoms and pyramidal signs did not predict a bad evolution. There was no relationship between evolution time and aggravation of the disease. There was no general correlation between clinical evolution and alterations in evoked potentials however the presence of bilaterally abnormal auditory evoked potentials was a predictor of bad prognosis. It is concluded that evoked potentials are relevant diagnostic tools in multiple sclerosis, specially when they detect subclinical alterations. PMID- 8191121 TI - [Mechanical reperfusion in acute myocardial infarction after failure of thrombolysis with intravenous streptokinase]. AB - AIM: to report the clinical evolution of four patients with acute myocardial infarction that were subjected to immediate coronary angioplasty due to the failure of reperfusion with streptokinase. BACKGROUND: the limitations for the use of thrombolytic agents, an accepted treatment of acute myocardial infarction, or their uncertain results in selected groups of patients has prompted the search for mechanical revascularization infarction subjected to thrombolytic therapy with streptokinase (1.500.000 U i.v.) after administration of hydrocortisone (100 mg i.v.) and acetyl salicylic acid (500 mg od). After 60 min thrombolytic therapy and due to hemodynamic depression with requirement of inotropic agents or the absence of clinical signs of reperfusion, the patients were subjected to coronary angiography. In view of a total occlusion or severe stenosis of the artery responsible for the infarction, an immediate transluminal angiography was performed to improve coronary flow. RESULTS: transluminal coronary angioplasty revascularized arteries with total occlusion or increased the lumen of those with severe residual stenosis. This was accompanied by reduction in pain and hemodynamic improvement. In one patient with complete AV block, conduction was improved and sinus rhythm was recovered. Echocardiographic controls showed preservation of ventricular function with persistence of segmental motility alterations. CONCLUSIONS: transluminal coronary angioplasty can be a revascularization alternative in patients with acute myocardial infarction and failure of reperfusion with systemic streptokinase. PMID- 8191122 TI - [Percutaneous mitral valvuloplasty in 2 pregnant women]. AB - In women with a significative mitral stenosis that become pregnant, medical treatment has limitations and surgical treatment is associated with maternal and fetal mortality. We report two pregnant women in whom a mitral valvuloplasty was performed in weeks 30 and 32 of pregnancy, using the single balloon Inoue technique. The indication for the procedure was the persistence of functional capacity IV heart failure in spite of hospital bed rest and the use of diuretics and beta-blockers. Basal mitral valvular area was 0.6 and 0.9 cm2 and improved to 1.7 and 1.8 cm2 after the procedure; six months later, the areas were 1.5 and 1.7 respectively. The procedure was well tolerated and was performed with abdominal and pelvic shielding. No complications occurred, which allowed hospital discharge in functional capacity I; they were readmitted for delivery, giving birth to two healthy girls. It is concluded that mitral valvuloplasty in safe and effective in pregnant women with mitral stenosis refractory to usual medical treatment. PMID- 8191123 TI - [Value of bronchoalveolar lavage in the diagnosis of pulmonary involvement in storage diseases]. AB - A 17 years old female with hepatosplenomegaly and pulmonary infiltrates since the age of four is presented. Sea-blue histiocyte disease, a sphingolipidosis, was diagnosed by liver biopsy, bone marrow aspirate and bronchoalveolar lavage. The relevance of bronchoalveolar lavage as a diagnostic method in cases of systemic diseases with pulmonary involvement is emphasized. PMID- 8191124 TI - [Therapeutic usefulness of antiandrogens]. AB - Antiandrogens are substances that block androgen receptors. The antiandrogenic action of some of these medications, as H2 blockers and some diuretics, was discovered as a collateral effect. They are used for the treatment of acne, hirsutism and seborrhea in women; they are also used in precocious puberty and sexual hyperexcitability states. The clinical usefulness of these drugs is unquestionable, but their prescription requires a through knowledge of their endocrinological effects. PMID- 8191125 TI - [Medical research in Chile: quantitative indicators]. AB - Diverse indicators were used to examine medical research in Chile. According to participation in Fondecyt projects, it was concluded that 420 persons were involved in medical sciences research and that 41.9% of them had no postgraduate title. During the eighties, there was a clear aging of the community dedicated to medical research. The scientific productivity was assessed through the inventory of publications in indexed journals. During the eighties, the number of articles in Clinical Medicine and Biomedical Sciences increased two-fold. The University of Chile published the greatest number of articles, followed by the Catholic University and, with a remarkable lower amount, other Universities. The impact of the published articles in Clinical Medicine and Biomedical Sciences was calculated from the citations that they generated from 1986 to 1988. Likewise, the articles registered in 1985 with the higher citation indexes were identified. PMID- 8191126 TI - [Changes and health. Adaptations of health systems to epidemiologic, socioeconomic, and politico-cultural changes]. AB - The basic concept of this article is the need to adapt the health systems to demographic and epidemiologic changes, considering that, at the present time the principal health problem of the world is adult health: non transmissible chronic diseases and accidents. As in the previous epidemiological cycle, when maternal and child health problems predominated, the aim must be put in health promotion and prevention, encouraging behavioral changes that decrease or avoid risk factors. The basic tools to incite the change are social communication, the introduction of health educational contents in formal education and the global reorientation of health systems from a predominance of curative actions towards preventive actions. At the present time, the analysis and debate of this topic has allowed the creation of multidisciplinary teams, integrated by epidemiologists, economists and sociologists, that will have to stratify the problems according to the needs and resources of a developing world. In Chile, a project searching for equity in the 35 poorest and postponed communities in the whole country is in operation. The most important result of this exercise has been the resemblance between the opinions of the community and of the public health specialists, which greatly helps the search for solutions. PMID- 8191127 TI - [Risk factors for low birth weight and intrauterine growth retardation in Santiago, Chile]. AB - An epidemiologic case-control study to ascertain the determinants of low birthweight was carried out in Santiago, Chile, from January to December 1989. The cases were defined as livebirths < 2500 g. The controls were livebirths > or = 2500 g of birthweight. All cases and a random sample (1:1) of controls were selected among 8,254 singleton births occurring at the El Salvador Hospital in the Eastern area of Santiago. These deliveries represented 50% of institutional deliveries in the area. Home deliveries (2%) and private hospital deliveries were not included in the study. Information was obtained from hospital medical records by six trained medical students. Some information could not be obtained from the hospital medical records. Thus the second step in data collection was the tracking of all the selected subjects to their referring neighborhood health centers. For the analysis, the data were divided into 3 case (outcome) categories: 453 subjects were the total case group. From these, 153 were the IUGR case group and 300 were the LBW preterm case group. The general control group consisted of 605 normal birthweight infants. 565 were the IUGR control group and 40 were the preterm control group. A total of 25 risk factors showed a significant crude odds ratio for at least one of the groups. In the multivariate logistic regression analysis eight variables: No. of pregnancies, previous adverse outcomes, previous LBW, pregnancy maternal weight, No. of visits, month of first prenatal care visit, maternal smoking and intrahepatic cholestasis of pregnancy, were significantly associated with LBW after adjustment by confounding. Eight risk factors: IUGR in previous pregnancies, Previous adverse outcome, Maternal smoking, intrahepatic cholestasis, maternal pregnancy weight, maternal height, month first prenatal visit, No. of visit, were significant to IUGR. Only two variables: pregnancy weight, divorced mother, were significantly associated with low birth weight in the preterm group. The most relevant risk factors were included in stepwise logistic regression models carried out for the outcome LBW for the general group, term group and preterm group, in order to adjust by confounding. Adjusted odds ratios were then obtained. Prenatal care related factors and maternal adverse obstetric factors were at higher significance for LBW in the general and IUGR groups. Only nutritional factors were related to LBW in preterm group. Women who delivered a LBW or IUGR infant were more likely to have fewer pregnancies, a history of previous LBW, lower prepregnancy weight and lower gestational weight gain. ICP was associated with an elevated risk of LBW that was independent of gestational age. PMID- 8191128 TI - [Molecular genetic study of cystic fibrosis in the Chilean population. Relationship to its clinical expression]. AB - Aiming to establish a genotype-phenotype relationship and to search a clinical expression in heterozygotes, 25 Chilean subjects with Cystic Fibrosis and 165 relatives were subjected to a clinical-molecular study. The most common mutations found worldwide were studied: delta F-508, G-542X, N-1303K, R-553X and G551D. Clinical and laboratory assessment comprised chest X-rays, spirometry, clinical evaluation, nutritional assessment, sweat test and carotenemia. Age at diagnosis was lower among homozygotes for the mutation delta F-508. In this group, Brasfield and Schawchman scores were better, probably due to an earlier initiation of treatment. No other differences were found among genotypic groups or relatives. Genetic markers indicated a higher european component of the sample, compared to the general Chilean population. PMID- 8191129 TI - [Evaluation of chromosome damage induced by X-rays in human lymphocytes]. AB - Aiming to assess the DNA damage induced by low doses of ionizing radiations, control and X-ray irradiated (10 rad) whole blood cultured lymphocytes were treated with the following G2 DNA synthesis and repair inhibitors: caffeine (caff), hydroxyurea (hu), aphidicolin (aphi) and 1-beta-D arabinofuranocylcytocine (ara C). The effects of each inhibitor or its combinations were assessed counting the number of chromatid breaks, which were considered equivalent to unrepaired lesions. Our results showed that 5 mM caff and 2.5 mM Hu were the inhibitors that separately produced the higher frequency of chromatid breaks. Likewise, the combination of 5 mM caff, aphi 5 micrograms/ml and ara C 1 microM, or 2.5 mM HU and 0.1 microM ara C, allowed to detect the highest number of induced lesions arriving G2 lesions. We therefore propose that the use of these two last inhibitor combinations, can be used as alternative methods to detect DNA damage induced by low levels of ionizing radiation, in lymphocytes of occupationally exposed individuals. PMID- 8191130 TI - [Mutagen extraction from bile of patients with inflammatory biliary pathology: Ames test using blue rayon]. AB - Gallbladder carcinoma is frequent in Chile. The aim of this study was to report the mutagenicity of whole human bile, using the Ames/Salmonella microsome assay with Salmonella typhimurium TA98. The bile of 19 patients, aged 23 to 64 years old, subjected to cholecystectomy was examined, and mutagen activity was found in 13 (72%). Mutagens were extracted using blue rayon and three dilutions for the eluted material from blue rayon were used (50, 100 and 200 ul). The best result was obtained using 200 ul. In some cases, the amount of revertive colonies was very high (over 5 times the control value). We propose that the bile from these patients possibly contains mutagenic substances with frame shift mutagenic activity and that these substances may be related to gallbladder carcinoma. Our results have addressed the importance of bile studies to elucidate the pathogenesis of gallbladder carcinoma. PMID- 8191131 TI - [Importance of gamma-interferon and DR expression in autoimmune thyroid disease]. AB - The purpose of this paper is to study some of the mechanisms by which antigen presentation, one of the first steps in the immune process, is modulated. Three different experiments are performed: a) Using thyroid tissue from patients operated on for Graves' Disease, spontaneous HLA-DR and TPO antigen expressions were measured through the Cytotoxicity Assay; these findings were correlated with the presence of antiTPO in the sera of these patients. It was found that only patients whose thyroid tissue spontaneously expressed both antigens had circulating antiTPO in their sera, thus demonstrating that dual expression is basic for antibody production. b) Blood samples from other Graves' patients were obtained; peripheral lymphocytes were isolated and cultured in complete media for 5 days, then supernatant was separated and IFN-g concentration was measured by a sandwich type RIA; the same procedure was done in 12 normal controls in order to compare the results. It was found that lymphocytes from Graves' patients secreted significantly more IFN-g than normal controls (20.9 +/- 13.54 U/ml vs 3.7 +/- 3.22 U/ml respectively, p < 0.001) confirming that they were sensitized, so this determination could be used as a marker of immune process, if other infectious conditions are excluded; also it was found that IFN-g hypersecretion persists once hyperthyroidism has been treated, pointing out that the immune abnormality is still present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191132 TI - [Evidence of a major gene in cleft lip/palate susceptibility by means of segregational analysis in the Chilean population]. AB - The most generally accepted model for cleft lip/palate not associated to specific syndromes has been the one that postulates multifactorial inheritance with a threshold. Recent studies using complex analytical techniques have suggested the existence of a major gene with decreased penetrance in its etiology. Some authors have postulated that only a fraction of all cases of non-syndromic CL (P) would be explained by a single major gene. Other cases may be due to different genes, to environmental agents or to the interaction between them. The present study tests the monogenic inheritance model for CL (P) using segregation analysis in a sample of 211 extended pedigrees collected through CL (P) affected probands. The hypotheses of an autosomic recessive gene was analyzed in 151 sibships (size 2 or more) using "Apert's" method, "maximum likelihood method", "singles method" and "sib's, method" (single incomplete ascertainment). Results obtained do not support the hypotheses of autosomal recessive inheritance. Instead, the hypothesis of an autosomal dominant mode of inheritance with low penetrance is not rejected when analyzing the proportion of normal and affected progeny in certain types of matings in a subsample of 30 extended pedigrees with two or more affected individuals. PMID- 8191133 TI - [Acquired resistance of M tuberculosis to the antitubercular drugs in Chile from 1988 to 1991]. AB - Acquired drug resistance appears in patients that are or have been in treatment for tuberculosis (relapses, abandons and failures). The aim of this study was to maintain an epidemiologic surveillance on the incidence of acquired drug resistance among previously treated patients and treatment failures. In 896 strains (518 in 1988 and 378 in 1991) coming from these type of patients, the pattern of sensitivity towards agents used in the treatment of tuberculosis was studied. There was an increase in the frequency of acquired resistance from 24.5% in 1988 to 32.3% in 1991. This increment was observed in the group of treatment failures, where the resistance to the combination streptomycin-isoniazid-rifampin had special relevance. This situation is epidemiologically and clinically negative since it generates primary resistance and chronicity. The increment in acquired resistance forces a revision of tuberculosis treatment, specially in its operational features. PMID- 8191134 TI - [Benzathine penicillin G and miocamycin in the treatment of children with streptococcal pharyngitis: a controlled therapeutic trial]. AB - The aim of this study was to compare the clinical and bacteriologic effectiveness of miocamycin (Miocamin, Merck) as compared to benzathine penicillin G in the treatment of streptococcal pharyngitis. One hundred forty nine patients (aged 2 to 15 years) with culture proven Group A streptococcal pharyngitis were randomly assigned to receive miocamycin (15 mg/kg/day bid per os) or one injection of 600,000 or 1,200,000 units of benzathine penicillin G. The clinical response was similar in both groups, in terms of fever duration (16 +/- 14 hours with miocamycin vs 13 +/- 13 hours with penicillin) and normalization of appetite (87.7% of children with miocamycin vs 95.8% of children with penicillin after three days). Bacteriologic eradication of streptococcus was achieved in 66% of children treated with penicillin and 32% of those treated with miocamycin (p < 0.001). We conclude that a single benzathine penicillin is more effective eradicating streptococcus pyogenes than miocamycin in children with streptococcal pharyngitis. PMID- 8191135 TI - [Autoimmune thyroid disease diagnosed during puerperium: evaluation 2 years later]. AB - This is a 2 years follow-up study of seventeen women who were found to have mild goiter and post-partum thyroid disease two years earlier in order to establish if post-partum thyroid disease is a self-limited entity or the relapse of a chronic pre-existing disease. When first studied, the 17 women had thyroid dysfunction (15 with hyperthyroidism and 2 with hypothyroidism). Eight women had also elevated antimicrosomal antibodies (AMA) titers and 9 were negative for AMA. In the present study, all women were reexamined for the presence of goiter, and free thyroxine index (FT4I), TSH and AMA were determined. Mild (grade I-II, less than 30 g) goiter was found in 11 women. Six out seventeen women, still had altered functional tests (3 with hypothyroidism and 3 with hyperthyroidism). The elevated AMA titers seen in 8 patients in the first study, remained high in 6 (1:100 1:25600). None of the 9 patients who in the first study had negative AMA changed to positive titers. Results indicate that post-partum thyroid disease is not always a self-limited entity. The presence of elevated AMA titers in the initial post-partum period can express a chronic thyroid disease compromise. In these patients a longterm clinical and biochemical follow-up is recommended. PMID- 8191136 TI - [The clock test: a simple method to assess dementia]. AB - AIM: to validate an easy and simple test to measure cognitive function: the clock drawing test. STUDY DESIGN: 138 hospitalized and free living elders (96 female, mean age 77.9 years) were studied. They were requested to draw a clock, using standardized instructions. The drawings were independently analyzed and scored by the authors. The Mini Mental State test was used as reference and the scores of both tests were correlated. RESULTS: there was a correlation of 0.73 between the scores of the clock drawing and Mini Mental State tests. Using a score of 7 points in tye clock drawing and 26 points in the Mini Mental State test as cut of points for the diagnosis of dementia, the former's sensitivity and specificity was 0.82 and 0.71 respectively. CONCLUSIONS: the clock drawing test appears as a simple and effective test for the initial assessment of cognitive functions in patients with suspected dementia. PMID- 8191137 TI - [Major adverse reactions to propylthiouracil in 586 cases of hyperthyroidism]. AB - Aiming to know the incidence and evolution of major adverse reactions to propylthiouracil in patients with hyperthyroidism, we performed a retrospective analysis of 586 patients treated between 1982 and 1992. All known complications associated to the use of propylthiouracil were considered major adverse reactions, when other causes were discarded. Eight patients (1.4% of the sample) had major adverse reactions: three had agranulocytosis, 3 hepatitis, 1 cholestasis and 1 vasculitis. All had a good evolution after discontinuing the drug. The patients with agranulocytosis were treated with antibiotics and the patient with cholestasis received prednisone. We conclude that major adverse reactions to propylthiouracil are infrequent, that they occur preferentially during the first months of treatment, earlier after reexposure and that there was no associated mortality. PMID- 8191138 TI - [Basedow-Graves disease development in 2 patients with primary hypothyroidism: exceptional development of the autoimmune thyroid disease]. AB - Autoimmune thyroid disease has multiple manifestations and its presentation may change with time. We report two patients with primary hypothyroidism due to Hashimoto's disease that unexpectedly, developed a hyperthyroidism due to Basedow Graves disease. This phenomenon may be explained by variations in the types and proportions of anti TSH receptor antibodies, that can stimulate or block thyroid gland function and growth. It is deducted that the hypothyroidism of these patients was not due to a definitive gland destruction, but to the action of function blocking antibodies. PMID- 8191139 TI - [Hemangiopericytoma: report of 4 cases]. AB - Hemangiopericytoma is an infrequent tumor of vascular origin derived from Zimmermann's pericyte cells. It is generally seen in adults of both sexes and its major risk is late recurrence, that occurs in up to 50% of cases. Its spread pattern is principally hematogenous. The management of the disease is similar to that of other sarcomas. Surgical treatment alone controls the disease in less than 30% of cases and the association of surgery and radiation therapy decrease the risk of local and distant recurrence. We report four cases of hemangiopericytomas, located in the prostate, retroperitoneum, supraclavicular space and lung. The four patients were treated with surgery and radiation therapy, three of them have had no evidence of recurrence after 1.5 to 6 years of follow up and the patient with the tumor located in the lung died one year after the operation. PMID- 8191140 TI - [Intermittent cecal volvulus. Report of 2 cases]. AB - In our country, acute cecal volvulus is responsible of 3.3% of mechanical large bowel obstructions. More than half of these cases have a history compatible with intermittent cecal volvulus, an usually overlooked diagnosis. The author reports two cases of intermittent cecal volvulus, treated in the last ten years. Both patients are female, aged 45 and 71 years old, with a history of 3 and 5 years of recurrent abdominal distention located in the right lower quadrant, that relieves spontaneously after the expulsion of gases or defecation. The symptomatology of the first cases was erroneously attributed to a concomitant colonic diverticulosis and the patient was subjected to a elective sigmoidectomy. The right colon and cecum was observed located in the right lower quadrant during the operation, and an appendectomy and a tube cecostomy for cecopexia were performed. The postoperative evolution was uneventful, and the patient is asymptomatic nine years later. The diagnosis in the second case was performed with a barium enema and a cecostomy for cecopexia was performed. The patient is asymptomatic two years later. The anatomical prerequisite for this condition is a lack of fusion of ascending colon to parietal peritoneum, which allows free rotation of this segment. The diagnosis must be suspected in patients with chronic and recurrent abdominal distention and must be confirmed with a barium enema. The surgical treatment consist in the fixation of the ascending colon. PMID- 8191141 TI - [Bone densitometry: is it a real clinical contribution?]. AB - Bone absorptiometry has allowed a real progression in the study of osteoporosis. Radiological dual-photon absorptiometry measures bone density with a precision near to 1%, which renders it useful for clinical use. Osteoporosis is specially prevalent among women older than 50 years. Since the disease is usually silent and there is not treatment to increase bone mass, its early detection is mandatory. The National Osteoporosis Foundation has specified the indications for bone absorptiometry. Although the routine measurement in postmenopausal women is not recommended, the author estimates that this guidance will change, due to the high prevalence of asymptomatic osteopenia in these women. PMID- 8191142 TI - [Dynamics of infectious disease transmission: a particular expression of predator prey dynamics]. AB - Infectious diseases in human populations are seldom seen as part of a permanently occurring phenomenon in natural ecosystems. Their relationships to predator-prey or host-parasite systems are not evident. The conceptual relationships between these systems is established through a basic deterministic model in this note, with special reference to populational fluctuations and epidemic recurrence. PMID- 8191143 TI - [Polydactyly in the Old Testament]. AB - The study of passage 2 Sam 21: 20-21 allows us to assert that the biblical writer registered a case of polydactyly, specifically a hexadactylia of the four limbs. The documental evidence certifies the presence of this orthopedic lesion in ancient times. It is probable that this was a case of post-axial, non crossed and non syndromic polydactyly. PMID- 8191144 TI - [Liver cirrhosis in Chile: epidemiologic considerations]. AB - Liver cirrhosis is an important public health problem in Chile, accounting for 5% of all deaths, proportion that has increased 24 fold in the last 60 years. Chile has the highest death rate for cirrhosis in America and the second highest in the world, after Hungary. The risk of death and hospitalization for cirrhosis has increased significantly between 1950 and 1970, stabilizing thereafter in values near to 50 hospitalizations and 30 deaths/year per 100,000 inhabitants. The risk for cirrhosis is higher among men and increases with age. Among people between 35 and 60 years of age, cirrhosis is the first or second cause of death and the third among those aged 60 to 69 years. The age of patients hospitalized for cirrhosis has increased from 42.7 years in 1950 to 55.5 in 1990. Among women, cirrhosis appears at older ages than in men. Mortality rates vary in the different regions of the country and range from 55 in Concepcion and Talcahuano to 8 per 100,000 inhabitants in Coquimbo. The certainty of Chilean information on cirrhosis and the evidences associating cirrhosis to alcohol consumption are discussed, being prominent the significant association between annual death rates for cirrhosis and wine production. PMID- 8191145 TI - [The school of Blest and Sazie]. AB - The biographies and professional contributions of William Blest, Lorenzo Sazie, Jose Joaquin Aguirre, Manuel Barros Borgono and Gregorio Amunategui are depicted. Dr Blest, arrived to Chile from Great Britain in 1823, helped to dignify the medical profession in Chile, in high disrepute by that times and was the first director of the Medical School, founded in 1833. Dr Sazie, coming from France, was the first dean of the Faculty of Medicine and remained in this position for almost 20 years. He was succeeded by Dr Aguirre a highly skilled surgeon that had three objectives: to bring up more and better physicians and to bring up professors for physicians. He was succeeded by Dr. Borgono that became head of the University of Chile in 1902. Dr Amunategui, being the dean of Medicine, also became head of the University in 1923. The works of Dr Armando Larraguibel and Dr Amador Neghme, who completed the cycle of the old Faculty are also outlined. PMID- 8191146 TI - [The first isolation in Chile of a free life amoeba in a user of contact lenses with severe keratitis]. PMID- 8191147 TI - [Chromosome aberrations in gallbladder adenocarcinoma]. PMID- 8191148 TI - [Biochemical markers of bone remodeling and bone density in healthy postmenopausal women]. AB - The aim of this study was to study bone turnover and density in postmenopausal women. One hundred healthy postmenopausal women aged 45 to 86 years, in whom menopause occurred between 3 months and 33 years before and were not receiving medications that could alter bone metabolism, were studied. Measurements performed were serum alkaline phosphatases, urine hydroxyproline/creatinine and calcium/creatinine excretion ratios and lumbar spine and femoral bone densities. Mean urinary hydroxyproline/creatinine excretion ratio was 39.5 +/- 11.9 (over 45 in 26% of women) and calcium/creatinine ratio was 0.11 +/- 0.08 (over 0.12 in 29% of women). At least one of these measurements were increased in 39% of women and no relationship of these values with age or length of postmenopausal period was found. Alkaline phosphatases were elevated in 9.6% of women. Twenty six percent of women had lumbar spine osteopenia and 10% femoral neck osteopenia. There was an inverse relationship between the length of hypoestrogenism and bone density. It is concluded that more than one third of studied women had biochemical evidences of bone resorption and that these women had a higher frequency of osteopenia than the general population. A decrease in bone density and an increase in bone resorption indices identify women with higher risk of osteoporosis that could be benefitted with an opportune treatment. PMID- 8191150 TI - [Diethylpropion in magisterial formulations. Influence of cellulosis derivatives on in vitro stability and availability]. AB - The aim of this work was to assess the degree of interaction between diethylpropion and some cellulosic derivatives widely used in anorexigenic prescriptions. Our in vitro results show that sodium carboxymethylcellulose and methylcellulose cause a significant degradation of diethylpropion, the first having a greater effect. Dissolution essays showed that the availability of the drug is vastly reduced by cellulosic derivatives. Provided the close relation between the dissolution and absorption characteristics of a drug, it is possible to predict that this association will result in a poor bioavailability. PMID- 8191149 TI - [Bone density and mineral content in normal men. Measurement by dual photon densitometry]. AB - The aim of this study was to measure whole body, L2 to L4 vertebral bodies and femoral neck bone density and mineral content, using a dual photon densitometer with a 153Gd source, in normal male subjects. One hundred twenty five males, aged 20 to 85 years, were studied. Subjects were separated, according to age in 5 year groups, with at least 10 subjects per group. Height did not show secular changes until 70 years of age, but a 9 kg increase in weight and a 3.8 kg/m2 increase in body mass index was observed. Lumbar spine bone density was 1.066 g/cm2 between 20 and 29 years and did not change with increasing age. In the same age group, femoral neck density was 1.034 g/cm2 and it decreased steadily after the age of 40 (slope = -0.003) with an annual loss of 0.23%. Total mineral content decreased from 2.477 g in the first age group to 2.316 g in subjects 70 years old or older. This represents a net loss of 6.5% in this period. Compared with normal females from a previous study, young men have similar spine and femoral neck densities than young women until the age of 50. In women over this age, there is a steady decline in lumbar spine density and the decrease in femoral neck density is more marked than in men. Also, total mineral content is higher in young men and its 6.5% loss with age is much lesser than the 31.6% loss observed in women. PMID- 8191151 TI - [Clinical profile of arterial hypertension in patients with cerebrovascular diseases]. AB - The aim this work was to assess retrospectively the history of hypertension in patients admitted for cerebrovascular diseases. Two hundred and forty eight patients were studied (69% with ischemic strokes, 24% with hemorrhagic strokes and 7% with transient ischemic attacks. 76% of cases had a history hypertension with an evolution of ten years or more in 81% of cases. No differences in the prevalence of hypertension was observed among the different types of strokes. Of the 139 patients in whom the severity of hypertension was registered, 37% had mild, 45% moderate, 15% severe and 3% systolic hypertension. Those with severe hypertension had a higher incidence of hemorrhagic stroke. Fundoscopic examination was abnormal in 81% of the 64 patients in whom it was performed, left ventricular hypertrophy was found in 62% of the 146 patients in whom it was investigated. 51% of patients were receiving anti hypertensive treatment and it was effective in 26% of them. Thirty one percent of subjects had old lesions in the CAT scan; these subjects had a similar prevalence of hypertension and effectiveness of treatment than patients without old lesions. It is concluded that a history of more than ten years of hypertension is a risk factor for cerebrovascular disease, that severe hypertension is mostly associated to hemorrhagic strokes and that only 26% of patients with stroke had and adequate anti hypertensive treatment. PMID- 8191152 TI - [Addiction to zipeprol. Report of 2 cases]. AB - Zipeprol is a non opioid antitussive agent derived from piperazine. In Chile there is an increasing abuse of this drug among youngsters. We report two cases, a 19-years old woman and a 42-years old male, both with personality disorders that used high doses of Zipeprol for hallucinogenic and sedative purposes. The woman had seizures due to the neurotoxic effects of the drug. PMID- 8191153 TI - [Progressive multifocal leukoencephalopathy in a patient with acquired immunodeficiency syndrome]. AB - We report a 28 year old heterosexual male with AIDS that presented with progressive motor disturbances and malaise. Light and transmission electron microscopy of a stereotaxic brain biopsy demonstrated a progressive multifocal leukoencephalopathy. This is a demyelinating infectious cerebral disease attributed to JC virus and must be considered in the differential diagnosis of central nervous system disturbances in AIDS patients. PMID- 8191154 TI - [Cerebral abscess caused by Toxoplasma gondii and AIDS. Report of a case with anatomo-pathological study]. AB - We report a 47 year old woman that presented to the hospital with an intracranial hypertension syndrome, a right hemiparesis and a several months history of progressive malaise and behavioral disturbances. During the hospital stay, positive HIV antibodies were detected and CAT scan showed a profound left parietal rounded hypodense lesion. The patient died 21 days after admission and the postmortem pathological study showed a deep abscess in the left basal ganglia, with recognizable Toxoplasma gondii trophozoites. PMID- 8191155 TI - [Hepatitis C virus in hemodialysis and kidney transplantation patients]. PMID- 8191156 TI - [Role of sex hormones in autoimmune diseases]. AB - There is increasing body of evidence to suggest that sex hormones may be closely involved in the pathogenesis of autoimmune diseases in humans. In the present article we discuss heteroimmune response differences between males and females and the roles of gender and sex hormones in autoimmune diseases in various species. The general conclusions are the following. Androgens and perhaps progestogens may protect from autoimmune disease; however oestrogens seems to have a dualistic effect on the immune system. Is has been demonstrated that oestrogens suppress antigen-specific T-cell dependent immune reactions while enhance B-cell activities. PMID- 8191157 TI - [Kidney papillary necrosis: experience with 61 cases]. PMID- 8191158 TI - [Health, power, and democracy. Notes for a primary care theory]. PMID- 8191159 TI - [Hypertension in rural communities. Study in the VIII Region, Chile]. AB - The aim of this work was to study the prevalence of hypertension in rural populations of the VIII region of Chile. Six thousand twenty four non institutionalized subjects. 14 years old or older, coming from eight randomly chosen rural communities were studied. Blood pressure was measured by trained personnel in two occasions within 30 minutes; in those classified as hypertensive, a third measurement was performed within 24 hours, eliminating alcohol intake and medications. Results show prevalence rates in the first, second and third measurement of 38.5, 30.8 and 22.8% respectively. The elimination of alcohol intake and medications decreased the prevalence in 3.9%. All the chosen communities has similar rates (19.8 to 21.2%) except Arauco, that had a significantly higher frequency of 31.9%. Zones of extreme ruralness had higher rates than small towns (23.8 vs 21.7%). There was a secular increase in the prevalence of hypertension from 4.9 in the 15 to 24 years old group to 57.8% among people 75 years old or older. Forty three percent of hypertensives were aware of such condition, 26.1% were receiving treatment and in 8.2% it was successful; all these figures were slightly better among women. PMID- 8191160 TI - [Are congenital malformations increasing? Comparative study of 2 periods: 1971 1977 and 1982-1991, in the maternity of the Clinical Hospital of the University of Chile]. AB - The aim of this work was to analyze the global incidence of congenital malformations at the Maternity of University of Chile Clinical Hospital in the periods between 1971 and 1977 and between 1982 and 1992. A significant and sustained increase in incidence was observed in the first period from 10.64 per 1000 born alive in 1971 to 33.79 in 1977. In the second period, the rates were stabilized at 60 to 70 per 1000 born alive. When comparing the incidence of 20 major or easily diagnosed malformations in the two periods, there was a significant increase in all during the second period. The possible causes of the increase in incidence are discussed, such as better diagnosis and registry, the use of ultrasound diagnosis and the incorporation of stillbirths to the registry during the second period. PMID- 8191161 TI - [Origin, development, and perspectives of public health institutions in Chile]. AB - This review gives information about the origin and development of the Public Health organisms in Chile, particularly the National Health Service, outstanding governmental health institution created in 1952, whose achievements were favored by the coordinated support of the University and the Chilean Medical Association. At the present time, their work is carried on by the National System of Health Services. The National Health systems have contributed to the improvement of population's health conditions, specially of the most vulnerable groups. Among other accomplishments, the life expectancy of the Chilean population has increased from 57 years in 1960 to 1972 years in 1990, and the general and infant mortality rates decreased from 12.6 to 6/1000 and from 120.5 to 16/1000 respectively. In the same period, the system has increased the coverage of its programs, specially those addressed to technical assistance of delivery, responsible parenthood, healthy child control, vaccinations, complementary feeding and sanitary education. The main limitation to the system's actions has been the restricted availability and the unequal distribution of resources assigned to health (about US$ 100 per capita). It is postulated that the implementation of a new Health and Social Welfare System (in study at the present time) should improve the efficiency and solidarity of health care. PMID- 8191162 TI - [Molecular characterization of the transferable resistance to amikacin in Enterobacteriaceae strains isolated from hospital infections]. AB - Sixty-three amikacin resistant strains of Enterobacteriaceae isolated in three hospitals from Santiago, between 1988 and 1990 were included in this study. The strains were multiresistant and harbored 1-5 plasmids. Fifty six isolates (88.9%) transferred amikacin resistance to E coli C600 receptor strain by conjugation. The transconjugants acquired a 11 kilobase-pair or a larger plasmid. The plasmids also encoded resistance to kanamycin, tobramycin, streptomycin and ampicillin. A DNA probe from the gene AAC (6')-I encoding an aminoglycoside 6'-N acetyltransferase, AAC (6')-I hybridized in Southern blot with plasmid DNA of the 10 Enterobacteriaceae strains tested, but not with the plasmid DNA of 8 amikacin resistant clinical strains of A baumannii. The results indicate that amikacin resistance in Enterobacteriaceae is due mainly to conjugative plasmids encoding an AAC (6')-I. PMID- 8191164 TI - [Diagnosis of von Willebrand's disease subtypes by the analysis of multimeric composition of plasma von Willebrand factor]. AB - The accurate diagnosis of the type of von Willebrand's disease (vWD) is important for a better understanding of its pathogenesis and for adequate treatment decision. We assessed the usefulness of the analysis of the multimeric composition of von Willebrand factor (vWF) in the diagnosis of vWD variants. vWF is purified by gel filtration and polyclonal, heterologous antibodies are raised in rabbits, which are immunopurified and radioiodinated. These are used to reveal, by autoradiography, the bands of vWF of various molecular weights separated by electrophoresis in agarose gels. This procedure reveals that 74 (80%) out of 92 patients with vWD suffer the classic type (I) of the disease, 6 (6.5%) type as IIA, 6 (6.5%) as IIB and 6 (6.5%) as III. The test is necessary for the correct classification of the patients, but is complex, laborious and expensive; it should be performed in patients with high probability of vWD or after the generic diagnosis of vWD has been made. PMID- 8191163 TI - [Pharmacological modification of prolactinemia. Effects on cellular immune function in normal subjects]. AB - Prolactin markedly influences cellular and humoral immunity in animals, but there is little information on its role in men. The aim of this work was to study the immune effects of pharmacological modification of prolactin levels in 5 healthy individuals. Peripheral blood mononuclear cell proliferative response to mitogens and antigens, interleukin-2 (IL-2) production, soluble and membrane IL-2 receptor expression in peripheral blood mononuclear cells and serum soluble IL-2 receptors were successively measured during normoprolactinemia, during bromocriptine induced hypoprolactinemia and during metoclopramide induced hyperprolactinemia. There was a significant increase in cellular proliferation during hypoprolactinemia when compared with hyperprolactinemia. No concomitant changes in soluble or membrane receptor expression or IL-2 production were observed. It is concluded that lymphocyte proliferative response to mitogens is dependent on prolactin levels in man and that this effects is not mediated by IL-2 or its receptors. These results may be potentially relevant in clinic since changes in serum prolactin have been described in different autoimmune diseases. PMID- 8191165 TI - [Indirect calorimetry and nitrogen balance in patients with elective craniotomy]. AB - The aim of this study was to assess resting energy expenditure and nitrogen excretion in patients with cranial injury. In 25 patients subjected to elective craniotomy and 23 healthy volunteers, energy expenditure was measured using indirect calorimetry and compared with estimations according to Harris-Benedict equations. During the second postoperative day, measured energy expenditure in patients was 100 +/- 19% (range 66-185) of estimation and 115 +/- 22% (range 76 159%) of measured values in control subjects. In sedated patients with flaccid muscular paralysis, measured energy expenditure was 82 +/- 12% of estimation and 94 +/- 15% of measured values in control subjects. Urinary urea nitrogen excretion in patients was 10.2 +/- 5.4 g/day and catabolic index was 6.8 +/- 5.1. Patients receiving corticoids had increased urinary urea nitrogen excretion and no differences in measured energy expenditure, compared to patients not receiving this medication. It is concluded that the great variability in measured energy expenditure and its lack of correlation with the degree of catabolism, set forth the need to perform an indirect calorimetry in these patients to plan an adequate nutritional support. PMID- 8191166 TI - [Functional esophageal exploration in the assessment of gastroesophageal reflux]. AB - During the past decade technologic progress has led to the increase use of oesophageal function testing, which is now available in clinical current practice. Ambulatory oesophageal pH monitoring is advocated as one of the best means for assessing the reflux of acid into the oesophagus. This technique can document abnormal gastro-oesophageal reflux (GOR) in patients with atypical symptoms or no endoscopic oesophagitis. The event marker allows to establish the correlation between occurrence of reflux and symptoms. This relationship can be quantified in the form of a symptom index; 24-hours pH monitoring can indicate objective criteria to define success of medical or surgical treatment. Oesophageal manometry analyses the lower oesophageal sphincter pressure and the oesophageal peristaltic function. This technique has a high prognostic value. The lower oesophageal sphincter pressure is not significantly different in patient with GOR but a severe hypotensive value is correlated with the severity of peptic oesophagitis. Peristaltic dysfunction is not specific but also increases with the severity of reflux disease. Pre-operative oesophageal manometry is recommended for identifying patients with oesophageal motility disorders and achalasia in whom anti-reflux surgery may precipitate postoperative dysphagia. The control of postoperative manometric data may be useful in the evaluation of surgery failure or recurrence of reflux symptoms. PMID- 8191167 TI - [gastroesophageal reflux in children, a curiosity or a disease?]. AB - The development of new techniques and their adaptation (miniaturization) to paediatric patients increase the understanding of the underlying pathogenic mechanisms of the classical gastro-oesophageal reflux (GOR) in infancy and childhood (mainly regurgitation). The more reliable detection of GOR is important in some non-digestive manifestations of disease. In the vast majority of infants, GOR follows a transitory and unconsequent course. However, in some cases, it can persist beyond the normal limit of time for maturation of the gastro-oesophageal junction (18-24 months), and is responsible for chronic complaints. In rare cases it can cause severe morbidity and mortality in the first months of life. PMID- 8191168 TI - [Anti-reflux surgery: indications, principles and contribution of laparoscopy]. AB - Surgery is indicated when gastro-oesophageal reflux disease (GORD) is resistant to medical treatment. Manometry, upper GI series, pH-metry, gastric emptying studies and gastric acid sampling are performed in order to demonstrate that GORD is caused by a deficient gastro-oesophageal valve mechanism, and hence that surgical treatment will be beneficial. The surgical principle is restoring an anti-reflux barrier by recreating a sufficient pressure gradient in the distal oesophagus, and by correcting the gastro-oesophageal Hiss. Nissen' fundoplication is probably the most efficient anti-reflux procedure. However, it can cause dysphagia, gas bloating and inability to burp. One hundred and fifty-six laparoscopic Nissen fundoplications have been performed by the author. Operating time average 120 min. No perioperative death was observed. There were 3 conversions to laparotomy and 4 peroperative complications: 1 gastric perforation, 2 lesions of the pleura and 1 liver laceration. Four postoperative complications occurred: 1 pneumonia, 1 necrosis of the wrap, 1 small bowel perforation and 1 obstruction due to migration of the entire stomach into the chest. Hospitalisation time ranged between 2 and 14 days (median 2), with a follow up of a median of 10 months. Long-term postoperative complications were: 1 recurrent heartburn 6 months postoperatively and 2 severe dysphagia. PMID- 8191169 TI - [Extradural hematoma following minor trauma]. PMID- 8191170 TI - [What if an artist calls at your office?]. AB - This paper deals with various complaints of performing artists. Gone are the days when such matters were brushed aside with the comment: "If it hurts, give it up!" To-day, osteoarthropathy among patients, Satchmo's syndrome, fiddler's neck and so on are treated scientifically in specific medical textbooks. Whilst the performing artist's activities have their aesthetic or even poetic aspects, the physical element of risk is nevertheless ever present. All this, only for your entertainment. Who has ever met a dancer who has never complained of tiredness? Even after a long professional training, before he has reached thirty years of age he will often have suffered from such ailments as inflammation of the big toe, fracture of the fifth metatarsal bone, dislocation of the trigone bone, etc. Following brief general remarks, the reader will find four specific sections devoted to the most common pathologies among performing artists, classified by profession. PMID- 8191171 TI - Physiopathological mechanisms of gastro-oesophageal reflux: is motility the clue? AB - Most of the physiopathological mechanisms of gastro-oesophageal reflux (GOR) disease are well known since many years. Nevertheless, it is very poorly understood why mechanisms differ from patient to patient. The relative importance of the factors involved is difficult to assess since they actually interfere with each other. The role of delayed gastric emptying related or not to increased abdominal pressure might be underestimated, as is the vicious circle of "GOR inducing GOR". PMID- 8191172 TI - Life expectancy of former elite athletes. PMID- 8191173 TI - Nutrition for young athletes. Special considerations. PMID- 8191175 TI - Eating disorders in female athletes. AB - Eating disorders can lead to death. The prevalence of subclinical and eating disorders is high among female athletes, and the prevalence of eating disorders is higher among female athletes than nonathletes. Athletes competing in sports where leanness or a specific bodyweight is considered important are more prone to develop eating disorders than athletes competing in sports where these factors are considered less important. It appears necessary to examine true eating disorders, the subclinical disorders and the range of behaviours and attitudes associated with eating disturbances in athletes, to learn how these clinical and subclinical disorders are related. Because of methodological weaknesses in the existing studies, including deficient description of the populations studied and the methods of data collection, the best instrument or interview method is not known. Therefore, more research on athletes and eating disorders is needed. Suggestions of the possible sport specific risk factors associated with the development of eating disorders in athletes exist, but large scale longitudinal studies are needed to learn more about risk factors and the aetiology of eating disorders in athletes at different competitive levels and within different sports. Further studies are required on the short and long term effects of eating disorders on athletes' health and athletic performance. PMID- 8191174 TI - Wrist injuries in sport. AB - The wrist is a complex joint that biomechanically transmits forces generated at the hand through to the forearm. The radial side of the wrist carries 80% of the axial load and the ulnar side the remaining 20% of the load. The incidence of wrist (and hand) injuries in the sporting population is approximately 25%. This tends to be higher in those sports using the hand and wrist, and when the potential for trauma is present. The injuries are divided into 4 categories: overuse, nerve (and vascular), traumatic, and weight-bearing injuries. Overuse injuries are common in sports involving the hand and wrist, such as racquet sports, netball, basketball and volleyball. Nerve injuries are more commonly compressive neuropathies, and are seen with cyclists who may compress the ulnar nerve in Guyon's canal. Vascular injuries are uncommon and usually result from a high velocity impact from balls. Traumatic injuries are the most common and are due to either a fall on to the wrist, a direct blow, or combination of a rotatory and torsional force. The weight-bearing injuries are more specific to gymnastics, and result from repetitive excessive compressive and rotational forces across the wrist. The pommel horse event is associated with a high incidence of wrist pain in male competitors. Arthroscopy of the wrist provides direct inspection of intra articular structures and diagnosis of conditions that may be unclear with other investigations. As techniques advance, more conditions may be treated arthroscopically and potentially facilitate an earlier return to sport. PMID- 8191176 TI - Ulnar neuropathy of the elbow. AB - Ulnar nerve entrapment is the second most common compressive neuropathy in the upper extremity because of its anatomy and superficial location. Major aetiological factors in the development of ulnar neuropathy of the elbow are compression, inherent anatomical structures, or lesions within the cubital tunnel. Extrinsic nerve compression may be elicited by acute or recurrent trauma. Nerve mobility may be impeded by congenital deformities. Ulnar nerve dysfunction has been associated with metabolic conditions, certain occupations and athletes involved in repetitive overhead activities. Ulnar nerve injuries may result in both motor and sensory abnormalities. Common symptoms include point tenderness, digital numbness and hand weakness. Evaluation of suspected neuropathy includes physical inspection for muscle atrophy, bony or muscle hypertrophy, deformities, digital clawing and a radiographic examination. Clinical techniques include the elbow flexion test, strength testing of hand intrinsics, flexor carpi ulnaris and digitorum profundus, and Tinel's sign. Sensory testing and McGowan's grading system may confirm the diagnosis and prognosis. Treatment options range from conservative (i.e. rest, splinting, nonsteroidal anti-inflammatory drugs, ice and abstinence) to radical surgical intervention (i.e. decompression, medical epicondylectomy and anterior transposition). In the throwing sport athlete, nerve involvement typically occurs along with other medical elbow problems. PMID- 8191177 TI - Common compartment syndromes in athletes. Treatment and rehabilitation. AB - Compartment syndromes in athletes are rare, but they can also be limb-threatening events. Chronic exertional compartment syndrome (CECS) is a less emergent form where symptoms recur with repetitive loading or exertional activities. CECS is the most common form of compartment syndrome seen in athletes. Acute compartment syndromes may also occur in athletes secondary to direct trauma or may develop from pre-existing CECS. The leg is by far the most common site of compartment syndrome in athletes. The thigh, forearm, and foot are the next most common sites, although any fascially limited compartment can be affected. Awareness of the clinical presentation and pathophysiology of compartment syndromes can help the examiner make a prompt and accurate diagnosis. The treatment of acute compartment syndrome is emergent while the treatment of CECS is not. Conservative treatment and rehabilitation can be successful in treating CECS. Acute compartment syndromes must be treated immediately with surgical decompression. With CECS, if conservative treatment fails, surgical decompression is also indicated. Some authors have suggested that the results of surgical fasciotomy and rate of return to sport for athletes with CECS has not been uniform. If the diagnosis is accurate and carefully documented, a high degree of success with athletes returning to sport can be expected. PMID- 8191178 TI - [What is your diagnosis? Diabetic cheiroarthropathy]. PMID- 8191179 TI - [In honor of Paracelsus--Einsiedeln 1993. Anniversary address and honoring of Paracelsus on Saturday, 6 November 1993, in Cloister Einsiedeln]. AB - The introductory address to the final ceremony of the anniversary of Einsiedeln attempts to show how a peregrine physician of the beginning New Age assesses the relation between the native place and the foreign country. A view on the life and work of Theophrastus von Hohenheim shows this relation to be full of tension and to be included in the relation of earthly pilgrimage to the heavenly home land. Paracelsus' spiritual greatness and the wideness of his points of view are thus evident from a vital factuality. PMID- 8191180 TI - [From The character of nature and the reign of time by Paracelsus]. AB - Based on the writings on philosophy of nature by Paracelsus, the depiction of his picture of the universe and man is tentatively deduced from his ideal of the 'light of nature'. Paracelsus uses traditional cosmology to isolate the latter from its rigid ordered structure and to interpret it as an order of processes. To this end he uses terms such as 'time' or 'timing' that not only explain human pathic states but also clarify the biochemical order of processes of all living matter. 'Nature' in the spirit of 'time' does not mean the static, completed creation but the dynamic imperative to man to transfigure himself and to transmutate an entire universe in conclusion. Finally the 'paths to the last days' resulting from the philosophy of 'nature and time' of Paracelsus expressing themselves in this vision of a 'transfiguration of the universe' and a 'glorification of the corpus' are touched. PMID- 8191181 TI - [Can medicine move mountains?]. AB - For the author involvement with Paracelsus demands consideration of both, socio cultural as well as historico-cultural aspects. Each generation has obtained a different picture of this famous physician from Einsiedeln. Around 1941 the progress initiated by Paracelsus has been emphasized, such as the assumed foundation of chemistry, chemotherapy, and the renewal of surgery, occupational medicine, balneology and many more. For the year 1941 (= 400th anniversary of Paracelsus death) a nationalistic perception of Paracelsus was typical. For National-Socialistic Germany, Paracelsus was the founder of a "German medicine" as a contrast to medicine oriented towards France and Jewish-Arabia. Paracelsus also was seen as a pioneer of the experiment and as opponent of medical dilettantism in a popular direction. The perception of Paracelsus of 1993 is completely different. Today Theophrastus from Hohenheim is seen in a post-modern perspective, not as the man of progress, but as one, who opposed to the medicine of his age a partial ancient natural medicine, including the arts of gypsies, witches and midwives. The magic and psychosomatic informations of Paracelsus are seen as precious compensation for losses that we had to accept in the progress of modern medicine. As a psychiatrist Paracelsus was involved with diseases that originated from a "misuse of credo". He reports about collective psychoses, for example those appearing in the group of anabaptists in St. Gallen. Misuse of credo derives from intended provocation of martyrium. To move mountains with one's faith is another pathologic imagination. A therapy should aim at the restitution of such a "mountain" moved by the ill patient. Paracelsus demands the greatest mercy in dealing with mentally ill patients. This disease is also a challenge for theology: "What gives harm to the body destroys the house of the eternal".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191182 TI - [Picture of Paracelsus, the physician--and we today]. AB - This article features the question whether Paracelsus and his dark, sometimes contradictory doctrine still includes some messages for modern physician. The lonely, pugnacious fighter from Central Switzerland remains today 'confused between favour and hatred from the parties'. Some contradictory examples shall outline controversies lasting for centuries. Subsequently Paracelsus' picture of nature, man and medicine is outlined, particular his meaning of nature and work of a good physician, but also his furious often unjustified overwhelming criticism about those physicians who went astray "in the labyrinthus medicorum". Sheep-physicians and wolf-physicians are confronted mercilessly and in a black and white scheme by this Lutherus medicorum. This likewise strange as well as also fascinating picture of a physician by this man of Hohenheim does not imply a clearly conceived temple inviting for an easy academic stroll. The sketch of a temple, however, serves as a symbol for the paracelsic science of healing: Philosophy, astronomy and alchemy are the three columns for the physician. These three columns are founded on virtue, the ethos of the physician. Religion the love for god, serves as a celestial roof. Finally the author expresses his opinion, that even today 500 years later, a modern, scientifically educated physician may profit from the philosophic and ethic principles of Paracelsus, who himself was a contemporary of a time of change like we are in our days. PMID- 8191183 TI - [Paracelsus in St. Gallen]. AB - Once, coming from Nurnberg, Paracelsus interrupted his journey and remained from 1531 to 1533 in the eastern part of Switzerland: First as personal physician of the severely ill mayor of St. Gall, Christian Studer, after the death of Studer (30. 12. 1531) he probably stayed in Roggenhalm near Buhler, a small village in the Canton of Appenzell. In most of the rare testimonies from citizens of St. Gall (Bartlome Schowinger, Johannes Rutiner, Vadian) about the man from Hohenheim he is described negatively as a rather unfavorable, unpleasant outsider. Vadian himself, to whom Paracelsus dedicated the third book of his "Opus Paramirum", obviously avoided him. In St. Gall Paracelsus wrote two prognostic scripts that were promptly printed in Zurich: The "Exposition of the Comet" and the "Exposition of the Arch of Peache". Rutiner tells in his diary about a (finally successful) surgical intervention on a hand operated by Paracelsus. Another successful treatment performed on a monk in December 1533, when he lived in Roggenheim, is registered in the expense-book of the abbot of St. Gall. PMID- 8191184 TI - [The heyday of neurology in the 19th century]. PMID- 8191185 TI - [The heyday of medicine and modernization in the 19th century]. AB - The numerous highlights of medicine in the 19th century represent an integral part of the successful development of science, especially with regard to the natural sciences. By the end of the century the sciences will have developed into an economic factor required and relied upon by state and society, after having originally functioned as the mere purveyor of meaning. This process should be interpreted as a component of the larger process of modernization. The main factors that constitute the necessary context within which medical science could develop were rationalization (M. Weber), professionalization, differentiation and individualization, all of which are the core elements of modernization, as well as governmental regulations and assistance and the growth of requests with regard to medical achievements. PMID- 8191186 TI - [The neuron theory: one of the main scientific achievements of the 19th century]. AB - The cell theory, enunciated by Theodor Schwann in 1839, stated that all tissues in the body are composed of individual cells. The theory gained immediate acceptance for all organs except for the nervous system where some basic problems were encountered, among them the difficulties in establishing the relation between nerve cells, nerve fibers and terminal branches. Deiters observations (1865) had provided evidence that the basic structure of a nerve cell was made up of a cell body, protoplasmic prolongations (dendrites), and a single long axon. This helped to define the nerve cell as the basic unit of the nervous tissue but it remained then to understand how the nerve cells are connected since they do not make direct contact through their cell bodies and are separated by the 'neuroglia'. Two fundamentally different views of the organization of neurons arose, one holding that neurons are individual and contiguous units, connected in chains to form specific pathways (His, Forel, Nansen, Ramon y Cajal), the other that thin nerve cell branches from continuous diffuse networks through which the neuronal activity propagates (Gerlach, Golgi). The key technological advance that led to the resolution of most of these uncertainties came in 1873 with the introduction by Camillo Golgi of a new method of staining individual nerve cells. In 1887, Santiago Ramon y Cajal stumbled on the Golgi stain and began an intense study of neuronal morphology throughout the nervous system. As far back as 1887 it was shown that the nervous system is not a mass of fused cells showing a common cytoplasm, but a highly intricate network of discrete cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191187 TI - [The founders of clinical neurology]. PMID- 8191188 TI - [The heyday of epileptology]. AB - The clinical symptoms of most types of epileptic seizures were already described in 1770 by Tissot. During the first half of the 19th century, his teaching was further developed and the nomenclature of epilepsy enriched. Rolando's description of the cortical convolutions as well as Bouchet's and Cazauvielh's observation of anatomical changes in the Ammon's horn of epileptic patients with psychical disturbances have prepared the way for the discovery of the role of local brain pathology as the cause of partial seizures. During the second half of the 19th century, Fritsch, Hitzig and Ferrier, by means of animal experiments, and Jackson, by means of clinical observation, discovered the motor function of the precentral cortex and that its irritation results in contralateral seizures. Independent of each other, Jackson and Sommer recognized that the initiation of what we nowadays call psychomotor or complex partial seizures lies within the limbic system. Caton's method of investigation brain currents in animal experiments, described in 1875, make possible in the 20th century to confirm Jackson's theory of epileptic seizures as sudden excessive discharges of the grey matter of the brain. Further advances of 19th century epileptology include: the etiological reclassification of epilepsies by Delasiauve, the first effective pharmacological (Bromide) and surgical therapies for epilepsy, the publication of classic textbooks on epilepsy by Gowers and Herpin as well as the setting up of specialized treatment centres for epilepsy. PMID- 8191189 TI - [Developments in neurophysiology in the 19th century]. AB - The rise of neurophysiology in the 19th century was kindled by Luigi Aloysius Galvani's revolutionary claim for animal electricity at the end of the preceding century. He was first challenged by Allessandro Giuseppe Antonio Anastasio Volta who showed that the muscle twitch in Galvani's experiment was the result of electric stimulation rather than of an enabled biological current. The controversy between Galvani and Volta became a predominant and stimulating issue among the scientists of the early century and found its ultimate elucidation only 40 years later by the pioneering work of Carlo Matteucci of Pisa and Emil Heinrich Du Bois-Reymond of Berlin, who both deserve the reknown as founders of modern neurophysiology. As the first influential promoter and mastermind of the experimental physiology, Francois Magendie of Paris primarily investigated the nervous system and inaugurated the lesion experiments to clarify specific functions of neural structures. Johannes Muller founded the German school of physiology with its eminent neurophysiological offspring: Du Bois-Reymond, Hermann Ludwig Ferdinand von Helmholtz, and Eduard Friedrich Wilhelm Pfluger. It was Helmholtz's merit to have for the first time precisely assessed the motor conduction velocity by measuring the time interval between two different stimulation sites of the sciatic nerve of the frog. In their brilliant work published in 1870 Gustav Theodor Fritsch and Eduard Hitzig demonstrated that appropriately located focal electrical stimulation of the exposed cortex of dogs induces movement of the contralateral limbs and unequivocally disproved the then prevailing dogma of holistic capacity of the hemispheres, which denied localised functions within the cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191190 TI - [Developments in neurology from the 19th to the 20th century with special reference to various contributions from Switzerland]. AB - Several modern concepts of the nervous system have developed since the last century: Their influence on modern neurology is traced by notes from biographies and the work of leading Swiss neurologists and neurobiologists. 1. Psychiatrists working in neuroanatomy: Auguste Forel, Constantin von Monakow, Bernhard Aloys von Gudden and Eduard Hitzig. 2. Anatomists who influenced the development of the "neurone-theory": Rudolf Albert von Kolliker and Wilhelm His Senior. 3. A practising physician developing "interactionism" as a basis for neurorehabilitation: Heinrich Simon Frenkel. 4. Behavioural aspects considered within a general framework of neurobiology: Walter R. Hess. 5. Neurosurgery: Hugo Krayenbuhl. PMID- 8191191 TI - [What is your diagnosis? Hyperostotic spondylosis (diffuse idiopathic skeletal hyperostosis [DISH])]. PMID- 8191192 TI - [Is aplastic anemia a preleukemic disease?]. PMID- 8191193 TI - [Symptom-oriented assessment in AIDS patients]. AB - The differential diagnosis of recently acquired cough, diarrhea, headaches, odynophagia and fever in AIDS-Patients is discussed. The aim is to find the most frequent, the treatable and the most dangerous diseases. We discuss the empirical and the symptomatic treatment in special situations. PMID- 8191194 TI - [The use of capillary videomicroscopy in the therapeutic assessment of acral vasospastic phenomena: microcirculatory effect of ketanserin and nifedipine]. AB - In-vivo videomicroscopy is one of the few noninvasive and clinically useful direct methods for evaluating the effect of a drug on microcirculation of normal and ischemic areas. By using nailfold videomicroscopy in conjunction with local exposure to cold air, the hemodynamic effects of ketanserine and nifedipine are reviewed in patients with primary Raynaud's disease. PMID- 8191195 TI - [Direct screwing in spondylolysis: results and observations on indications]. AB - Ten patients suffering from persisting low-back pain underwent direct repair of spondylolysis L5 with hook screws. At a follow-up three to four years after the operation, four patients showed good and six unsatisfactory results. Four patients had a secondary procedure. Average age was relatively high in the study group compared with the literature, and pain tended to be chronic. In five of the six patients with a poor clinical result, radiological consolidation of the lytic defect could not be demonstrated. We are discussing indications based on a literature review. PMID- 8191196 TI - [Chronic spondylogenic pain syndrome--tb-spondylitis?]. AB - The incidence of tuberculosis is increasing in many of the industrialized countries, mainly due to the spreading of HIV infections, the migration from countries with high prevalence of tuberculosis and possibly through the increase of the aged population. In 10 to 25% of the cases, tuberculosis manifests itself in extrapulmonary organs. One of the most frequent locations is the spine. The symptoms of the TB spondylitis are unspecific, and the course is creeping, which makes an early diagnosis difficult. Because of the frequent, severe complications, this must be attempted. In patients belonging to a risk group or with known exposition to tuberculosis and vertebral pain, the TB spondylitis must be included in the differential diagnosis. Combined chemotherapy is the key to successful therapy and can make surgical interventions or immobilization unnecessary. Two cases are presented, and the disease of the TB spondylitis is discussed. PMID- 8191197 TI - [A case from practice (293). HIV-infection and histoplasmosis]. PMID- 8191198 TI - Effect of continuous heat exposure on sleep during partial sleep deprivation. AB - This study examined the effects of continuous heat exposure on sleep structure during a partial sleep-deprivation regime. The experimental protocol was divided into three periods. After a baseline period (5 days and nights at 20 degrees C), the sleep of the subjects was restricted to the second half of the night (3 a.m. 7 a.m.) for four consecutive nights. The restricted-sleep period was followed by two recovery days and nights. During the deprivation and recovery periods, the ambient temperature was 20 degrees C for six of the 12 subjects and 35 degrees C for the others. Sleep, esophageal and mean skin temperatures were continuously recorded. At 20 degrees C, the expected effect of sleep debt was apparent. There were significant reductions in time spent awake and in latencies for sleep and stage 4 sleep. The duration of stage 4 sleep significantly increased during the four successive restricted-sleep nights, whereas esophageal temperature significantly decreased over the successive days. When heat was added, esophageal temperature decrease was weakened, and the significant increase in stage 4 duration seen at 20 degrees C was not found. The findings suggest that the heat load imposed in our experimental condition has a suppressive effect on sleep stage 4 increase, which is induced by sleep restriction. The hypothesis that an increase in this sleep stage serves as a mechanism for energy conservation should be also considered. PMID- 8191199 TI - Prolactin secretion and sleep. AB - To clarify the relationship between prolactin (PRL) secretion and sleep, three experimental procedures were employed and secretory rates were estimated from plasma levels using a deconvolution procedure. Eight healthy young men participated in two 24-hour studies, one using normal night sleep and one using delayed sleep, to determine the influence of sleep as a whole on the PRL rhythm. Another group of 24 subjects underwent a 1-night study to investigate the relationship between PRL secretion and the internal sleep structure. The influence of sleep quality was studied in two more groups of eight subjects. Secretory rates were calculated by deconvolution from plasma PRL measured at 10 minute intervals. Sleep was recorded polygraphically in all experiments. PRL secretory pulses occurred throughout the 24-hour cycle without significant variation in frequency, but with enhanced pulse amplitude for both night and day sleep periods. Sleep onset was rapidly followed by an increase in secretion, and awakenings coincided with an immediate offset of active secretion. Analyzing the association between secretory pulses and sleep stages demonstrated that PRL secretory rate is low at the time of rapid eye movement sleep onset. Sleep quality appeared not to affect the PRL secretory profile. These results confirmed that PRL secretion is enhanced during the whole sleep period, as inferred from plasma levels. Considering secretory pulses provides a precise determination of the temporal relations between PRL and sleep structure and demonstrates that occasionally poor sleep does not influence PRL secretion in normal humans. PMID- 8191200 TI - Scoring transitions to REM sleep in rats based on the EEG phenomena of pre-REM sleep: an improved analysis of sleep structure. AB - Algorithms for scoring sleep/waking states and transitions to REM sleep (NRTs) in rats are presented and validated. Both algorithms are based on electroencephalographic (EEG) power in delta (0.5-4.0 Hz), theta (6-9 Hz) and sigma (10-14 Hz) frequency bands, and electromyogram (EMG) intensity. Waking is scored when EMG intensity is high or (sigma power).(theta power) is low. Nonrapid eye movement (NREM) sleep is scored in nonwaking epochs having high (delta power)/(theta power). Rapid eye movement (REM) sleep is scored in nonwaking epochs having low (delta power)/(theta power). NRTs are identified by the EEG phenomena of the pre-REM sleep phase of NREM sleep. Algorithms are validated by comparison with records scored independently by two investigators based on visual examination of EEGs and EMGs. The sleep/waking-state scoring algorithm produces greater than 90% agreement with visual scoring. The NRT-scoring algorithm produces 88-92% agreement with visual scoring. Scoring NRTs based on the phenomena of the pre-REM sleep phase of NREM sleep, instead of relying solely on REM sleep expression for identification of REM sleep onset, reveals a significant population of brief REM sleep episodes that are ignored by most sleep cycle analyses and allows independent quantification of REM sleep timing and maintenance. PMID- 8191201 TI - A computerized method for detecting episodes of wakefulness during sleep based on the alpha slow-wave index (ASI). AB - A method for the automatic detection of episodes of wakefulness during sleep is presented. The algorithm is based on the evaluation of the alpha slow-wave index (ASI), a measure that has been developed to detect fluctuations of vigilance in daytime pharmaco-electroencephalogram studies. Its application to sleep data was validated with polysomnographic recordings from 16 elderly insomniacs and 16 young healthy subjects. The rate of agreement between the computerized procedure and the visual scoring of wakefulness was 94.0% for the insomniacs and 96.9% for the healthy subjects. The decision criterion used by the computer allowed the definition of a subject-adapted threshold for the detection of wake episodes. The method opens new perspectives for the automatic analysis of continuous 24-hour sleep-wake recordings. PMID- 8191203 TI - Quality adjusted life years added by treatment of obstructive sleep apnea. AB - We assessed the impact of treatment with nasal continuous positive airway pressure (nCPAP) on the quality of life of 19 patients with obstructive sleep apnea (OSA). We measured the utility for the patients' health states before and with treatment using the standard gamble approach. The study group had an average age of 57 years and had been on treatment for a mean of 9.5 months. For all the patients, the polysomnographic indicators of OSA disease severity improved markedly with treatment. For nine of the 12 symptoms most commonly associated with OSA, the patients reported improvement during treatment. The mean utility and the standard deviation obtained with the standard gamble method were 0.87 +/- 0.17 on treatment and 0.63 +/- 0.29 pretreatment. The difference in utility between treatment and pretreatment health states was combined with the life expectancy of each patient to generate the number of quality adjusted life years (QALYs) considered equivalent to the impact of treatment. This resulted in an average gain of 5.4 QALYs. When we related this impact to the cost of treatment, we obtained a cost-utility ratio between Can $3,397 and Can $9,792 per QALY added. These costs are relatively small when compared to the cost per QALY for many other clinical interventions. Hence, nCPAP clearly offers the prospect for a well-tolerated therapy with a very favorable cost-utility ratio. PMID- 8191202 TI - Comparisons of EEG sleep state-specific spectral values between healthy full-term and preterm infants at comparable postconceptional ages. AB - Differences in state-specific electroencephalographic (EEG) spectral values are described between groups of preterm and full-term neonates at comparable postconceptional term ages. Eighteen healthy preterm neonates of < or = 32 weeks gestation were selected from an inborn population of a neonatal intensive care unit. Twenty-four-channel recordings were obtained at a full-term age and compared with studies of 22 healthy full-term neonates. The initial three hours of each 12-hour study were recorded on paper from which EEG sleep state scores per minute were visually assessed. Six mean spectral values (i.e. total EEG, electromyogram, delta, theta, alpha and beta energies) were calculated from each corresponding minute of digitized data, which was also assigned one of six EEG sleep states. Each neonatal group displayed statistically significant differences among sleep-state segments for all spectral values. The alpha- and beta-range spectral values of the preterm group, compared to the full-term control group, were lower during all sleep state segments. Spectral values for the theta band were lower during both quiet sleep segments only, whereas spectral values for delta were lower during all sleep stages, except trace-alternant quiet sleep. Significant differences in EEG spectral values were noted among states of sleep for both preterm and full-term infants of similar postconceptional term ages. These data also suggest differences in central nervous system maturation between neonatal populations. These findings strengthen our previously stated contention that there is a functional alteration in brain development of the preterm infant as reflected in sleep organization that results from a prolonged extrauterine experience and/or prematurity. PMID- 8191204 TI - Effect of inhaled 3% CO2 on Cheyne-Stokes respiration in congestive heart failure. AB - Cheyne-Stokes respiration (CSR) in severe stable congestive heart failure (CHF) may be associated with significant nocturnal arterial oxygen desaturation and sleep disruption. Previous investigations of inhaled CO2 in CSR have been uncontrolled and of short duration, sleep has not been monitored electroencephalographically, and most patients studied have had neurological disease with or without cardiac disease. The purpose of our study was to document the effects of inhaled CO2 on CSR in patients with severe stable CHF (left ventricular ejection fraction < 35% and NYHA class 3 or 4 dyspnea) in controlled all-night polysomnographic studies. Six patients were studied for 3 nights and days: adaptation, control and inhalation of CO2. These patients received a constant F1CO2 = 0.03 in air (with a 4-5 mm Hg increase in PaCO2) on night 3. This caused virtual abolition of CSR as reflected by CSR duration/total sleep time (62-2.2%; p = 0.0012) and CSR duration/nonrapid eye movement (NREM) sleep time (73-2.4%; p = 0.00064), and NREM apnea index was reduced from 33.5 to zero (p = 0.026). The apparatus used to accurately control F1CO2, however, was intrusive and some features of sleep structure such as sleep latency were adversely affected. We conclude that inhalation of CO2 with a constant F1CO2 = 0.03 virtually eradicates CSR in all-night polysomnographically monitored studies in patients with severe stable CHF. The clinical significance of these findings remains to be determined. PMID- 8191205 TI - Daytime sleep inertia in narcolepsy-cataplexy. AB - Eight volunteers with narcolepsy-cataplexy participated in a study of scheduled naps and performance. Sleep inertia was examined following five "short" naps of 5% and a single "long" nap of 25% of total 24-hour sleep time as determined by prior sleep log data. Contrary to some subjective reports, short naps (mean duration of just under 30 minutes) were accompanied by sleep inertia in narcoleptics. As measured by the descending subtraction task, this sleep inertia was at times quite prolonged and lasted 20 minutes after waking from midday short naps, which ended on average at 1555 hours. In addition, sleep inertia, as measured by both the descending subtraction task and the four-choice reaction time test, was evident throughout both afternoon and evening short naps; however, it was completely absent from reaction-time test results immediately following the single long nap, which ended on average at 1640 hours. Sleep inertia was maximum after slow-wave sleep arousals and was minimal or absent following the first short nap, which also contained the highest amount of rapid eye movement sleep of all naps. PMID- 8191206 TI - Are breathing disturbances in elderly equivalent to sleep apnea syndrome? PMID- 8191208 TI - Bibliography of recent literature in sleep research. PMID- 8191207 TI - Contribution to a controversial discussion: the dynamics of delta/beta activity during sleep. PMID- 8191209 TI - Current trends in the dental laboratory industry: gaining recognition as para professionals. PMID- 8191210 TI - What a dentist should know about dental technology certification. AB - This article is one in a constructive series about how dental laboratories and dentists interact. It is aimed toward improving functional relationships to serve the public better. Readers are encouraged to respond in writing about our laboratory series. All members of our professions, including dental laboratory owners, dental technicians and dentists, are invited to participate. PMID- 8191211 TI - A guide to managing your laboratory in the 1990s and beyond. PMID- 8191212 TI - Palladium-based dental alloys in the '90s. AB - The paper will explain metallurgical background on palladium-based dental alloys by discussing the "other elements" typical to these alloys, both C&B (non porcelain Crown and Bridge) and PFM (porcelain fused to metal). Examination of how the elements work will help explain the differences among various Pd-based alloys. PMID- 8191213 TI - The dimensions of color related to dental porcelain and translucency. PMID- 8191214 TI - Laboratory fabrication of an implant supported and retained milled bar overdenture. PMID- 8191215 TI - Marketing your winning image. PMID- 8191216 TI - CDT today: all about NBC test scheduling. PMID- 8191217 TI - Decreased CD8-p56lck activity in peripheral blood T-lymphocytes from patients with hereditary haemochromatosis. AB - Hereditary haemochromatosis (HH) is an autosomal recessive disease linked to certain MHC class-I specificities. The disease is characterized by increased iron absorption and, in some patients, abnormally low numbers of CD8+ T cells in the periphery. We were interested in whether CD4- and CD8-associated p56lck kinase activities were altered in patients with HH. In a study of 18 patients with HH (with and without low numbers of CD8+ cells), the level of autophosphorylation of the CD8-associated p56lck as well as its phosphotransferase activity, as determined by phosphorylation of an exogenous substrate, was significantly reduced by two- to three-fold relative to a control population of 23 healthy blood donors (P < 6 x 10(-7). CD8-p56lck activity was decreased in 16 out of 18 patients (ranging from 1.5- to 10-fold decrease). By contrast, the level of CD4 p56lck activity did not show an overall decrease relative to controls. In addition to an occasional decrease in the amount of CD8-associated lck, HH patient-derived T cells showed a consistent decrease in the relative CD8-p56lck specific activity. Immunofluorescence staining showed further that the difference could not be accounted by a discrepancy in the expression of CD8 alpha alpha or CD8 alpha beta complexes or MHC class I molecules. Decreased CD8-p56lck activity was seen both in patients undergoing intensive phlebotomy treatment and in patients in maintenance therapy (i.e. patients who had reached normal levels of iron stores), indicating that this abnormality does not appear to be corrected by iron depletion. To our knowledge, this is the first demonstration of an abnormality in a src-like receptor associated kinase in a human disease state linked to MHC class-I antigens. PMID- 8191218 TI - The B-cell adhesion molecule CD22 is cross-species reactive and recognizes distinct sialoglycoproteins on different functional T-cell sub-populations. AB - CD22 is a B cell lineage restricted cell-surface adhesion glycoprotein which recognizes ligands on human T and B cells and cell lines. A soluble recombinant form of human CD22 (hCD22Rg) has been used to identify and characterize CD22 specific ligands on human T cells, one of which has been shown to be the receptor linked phosphotyrosine phosphatase CD45. Because CD45 plays a pivotal role in lymphocyte activation, we assessed whether human CD22 might display cross-species reactivity with CD45. In the study presented here we demonstrate that human CD22Rg recognizes several murine cell-surface sialoglycoproteins, including CD45, containing sialic acid in alpha 2,6 linkage. Furthermore, hCD22Rg recognizes different ligands on functionally distinct T helper-cell subpopulations and selectively binds medullary thymocytes in vivo. Our results confirm and extend previous observations that CD22 is a sialic acid-binding lectin which interacts with CD45 and other glycoproteins capable of presenting alpha 2,6-linked sialic acid in a manner that promotes high affinity binding. The cross-species reactivity of CD22 with its ligands underscores the potential physiologic importance of CD22-mediated lymphocyte interactions. PMID- 8191219 TI - Mannan-binding protein and bovine conglutinin mediate enhancement of herpes simplex virus type 2 infection in mice. AB - A broad range of plant lectins have recently been shown to inhibit the infectivity of herpes simplex virus type 1 (HSV-1) in vitro. We decided to investigate the role of mammalian lectins in infection with herpes simplex virus. Two lectins, conglutinin and mannan-binding protein (also called mannose-binding protein, MBP), belonging to the collectin family of lectins, were examined. Four week-old BALB/c mice were injected subcutaneously with 100 micrograms bovine conglutinin or 50 micrograms human MBP 1 day before intravenous infection with 5 x 10(4) PFU of herpes simplex virus type 2 (HSV-2). A three-fold increase in virus titre of the liver was observed on day 3 of the infection in the mice pretreated with conglutinin or MBP, whereas no effect was seen on days 1 and 5. In a standard plaque assay using Vero cells we were not able to demonstrate reproducibly either infection inhibition or infection enhancement, when virus was pre-incubated with differing concentrations of the collectins. The concentrations used were similar to those used by us in vivo, and by others in in vitro experiments showing inhibition of the infectivity of HSV-1 with plant lectins. In an ELISA with HSV-2 antigens captured on anti-HSV-2 antibodies, calcium-dependent and carbohydrate inhibitable binding of the collectins was observed. Our results indicate that the effect of endogenous mammalian collectins in vivo may not be neutralization as suggested by the data using plant lectins. Instead, the previously described opsonizing activity of the mammalian collectins may provide the virions with an alternative port of entry into cells leading to infection enhancement. PMID- 8191220 TI - The treatment of autoimmune disease in (NZB/NZW)F1 mice with syngeneic photomodulated splenocytes. AB - (NZB x NZW)F1 (B/W) mice spontaneously develop a disease which is remarkably similar to systemic lupus erythematosus (SLE) in humans. This disease is characterized by the appearance of autoantibodies to double-stranded (ds)DNA and the subsequent development of fatal glomerulonephritis. The prophylactic treatment of B/W mice with syngeneic photomodulated autoimmune spleen cells was found to significantly improve survival, and to inhibit the outgrowth of autoreactive B cells and the production of high-titre IgG anti-dsDNA antibodies. The function of the autoreactive T cells in vivo, however, did not change significantly. Our findings suggested a novel treatment for spontaneously occurring autoantibody-related autoimmune diseases. PMID- 8191221 TI - Relevance of antibody valency in EGF receptor modulation. AB - Binding characteristics of a monovalent bispecific monoclonal antibody (bsMoAb), which recognizes both epidermal growth factor receptor (EGF-R) and drug doxorubicin (DXR) were compared with those of the parental bivalent MoAb directed against the EGF-R binding site. Scatchard analysis indicated that both MoAbs bound to EGF-R-overexpressing A431 cells with the same affinity. In tracer amounts, both MoAbs also displayed the same capacity to be internalized after binding to the cell surface. However, when the MoAbs were used at saturating concentrations, down-modulation of the receptor was greater with the bivalent MoAb. The bivalent MoAb also inhibited proliferation of A431 cells both in vitro and in vivo whereas the bsMoAb was inhibitory only in vivo. These data suggest that MoAb bivalency is required for EGF-R down-modulation and in vitro cell growth inhibition. PMID- 8191222 TI - Interaction of in vitro- and in vivo-generated cytotoxic T cells with SV40 T antigen: analysis with synthetic peptides. AB - Virus-specific cytotoxic T cells recognize antigens in the form of peptides (8 or 9 amino acids long) bound to MHC class-I molecules. Exposure of unprimed murine splenocytes to synthetic peptides of viral antigens elicits primary CTL in vitro. The fine specificity of such CTL as well as the correlation between binding affinity of peptides to class-I molecules and CTL induction was analysed using synthetic peptides corresponding to overlapping and distinct amino-acid residues in SV40 T antigen (Tag) Db-restricted T-cell epitopes I, II-III, and V. The peptides induced cross-reactive CD8+ primary CTL in splenocytes of naive C57 BL/6 mice. This reactivity was seen regardless of the peptides allelic anchor motifs or their abilities to stabilize empty class-I molecules. However, none of the primary CTL and CTL lines lysed Tag-expressing cells. In contrast, CTL generated in vivo by immunizing mice with Tag-expressing cells recognized endogenously processed Tag as well as synthetic peptides. The peptides recognized by these CTL depended on the intracellular concentration of Tag antigen in the immunizing cells. The reactivity of these CTL was peptide specific as shown by a functional peptide competition assay. Moreover, three peptides bound to and were recognized in the context of both Kb and Db molecules. These results have revealed a flexible disposition of MHC class-I molecules with regard to peptide binding and also reflected lack of correlation between binding affinity to class-I molecules and the capacity of peptides to induce primary CTL or to serve as potential targets. The significance of these findings in relation to identifying major T cell epitopes using allele specific peptide motif and in vitro maintained CTL clones is discussed. PMID- 8191223 TI - 3,3',4,4'-Tetrachlorobiphenyl inhibits proliferation of immature thymocytes in fetal thymus organ culture. AB - The environmental pollutant 3,3',4,4'-tetrachlorobiphenyl (TCB) leads to thymic atrophy and immunosuppression, the former possibly causing the latter. TCB binds to the cytosolic aryl-hydrocarbon receptor (AhR) and transforms it into a DNA binding state. The development of fetal thymocytes is severely affected by TCB and other AhR-binding xenobiotics, leading to a skewed pattern of thymocyte maturation stages. Murine thymocyte proliferation after exposure to TCB was studied in fetal thymus organ culture (FTOC). C57BL/6 fetus thymic lobes from day 15 of gestation were explanted and grown for 2, 4, 6, and 8 days in organ culture in the presence or absence of 3.3 microM TCB. Subsets of thymocytes were defined by CD4 and CD8 surface markers, and their cell cycle was analysed by DNA staining with 7-amino-actinomycin D (7-AAD). Exposure of fetal thymi in vitro to 3.3 microM TCB significantly reduced the total number of thymocytes, and fewer thymocytes were in S/G2M phase. The inhibition of cell proliferation induced by TCB treatment affected mainly the CD4-CD8- (double-negative, DN) and CD4-CD8+ (single-positive, SP) subsets, and these inhibition appeared mainly in more immature thymocytes, i.e. DNCD3- and CD8+CD3- subpopulations, whereas no effect of TCB on CD4+CD8+ (double-positive, DP) cell proliferative activity was observed. Analysis of the relation of cell proliferation and development of subsets in differentiating fetal thymocytes suggests that TCB enhanced thymocyte differentiation into mature CD8+ cells. PMID- 8191224 TI - Phenotypic characterization of the human mast-cell line HMC-1. AB - The cell line HMC-1, derived from a patient with mast cell leukaemia, is the only established cell line exhibiting a phenotype similar to that of human mast cells. This paper reports on a detailed characterization of the expression of a panel of markers for various types of immature and mature haematopoietic cells in the HMC 1. We also studied the potential of HMC-1 to differentiate upon treatment with conditioned media from the human T-cell line Mo, retinoic acid or DMSO. HMC-1 was found to express several mast cell-related markers. A high expression of Kit, the receptor for stem-cell factor, was detected. The majority of the cells were stained with a MoAb against the mast cell-specific serine protease tryptase. Of particular interest was the finding that beta-tryptase mRNA, but not alpha tryptase mRNA, was expressed in HMC-1. Using enzyme-histochemistry we were able to show that the beta-tryptase was enzymatically active, indicating that tryptase can form active homotetramers. Both heparin and chondroitin sulfate were found to be present in approximately equal amounts. HMC-1 lacked surface expression of the high-affinity IgE receptor, which was confirmed by the absence of mRNA of the alpha- and beta-chains of the IgE-receptor complex. However, a strong expression of the gamma-chain of the IgE-receptor complex was detected. A positive staining of the monocyte/macrophage marker CD68 was obtained, as well as a strong hybridization signal for the eosinophilic/basophilic-related differentiation marker the Charcot-Leyden crystal. Treatment of HMC-1 with conditioned media from the human T-cell line Mo, retinoic acid or DMSO induced only moderate changes in the surface or intracellular expression of the studied markers. The agents tested neither induced any of the monocyte/granulocyte markers examined, nor expression of the Fc epsilon RI alpha-chain. PMID- 8191225 TI - Antisense oligodeoxynucleotides for IL-2, c-myc and transferrin receptor synchronize mitogen-activated lymphocytes in the G1 phase. AB - In order to clarify the role and interrelationship of c-myc, interleukin-2 (IL 2), and transferrin receptor (TfR) expressions on PHA-stimulated lymphocyte proliferation, we examined the effects of antisense oligodeoxynucleotides directed against c-myc, TfR, and IL-2 mRNAs on DNA synthesis and cell-cycle phase. Exposure of PHA-stimulated lymphocytes to each antisense oligomer resulted in approximately 75-80% inhibition of DNA synthesis. TfR expression was not inhibited in PHA-stimulated lymphocytes by c-myc or IL-2 antisense oligonucleotides, suggesting that the expression of c-myc, TfR, and of IL-2 is regulated by an independent mechanism. All three antisense oligonucleotides for c myc, TfR and IL-2 synchronized mitogen-activated lymphocytes to the G1 phase as assessed by morphologic blast formation and cell-cycle phase analysis. PMID- 8191226 TI - High serum-soluble interleukin-2 receptor is not associated with the immunosuppression in diffuse cutaneous leishmaniasis. AB - Diffuse Cutaneous Leishmaniasis (DCL) is a rare complication of Leishmania aethiopica-induced cutaneous leishmaniasis which is associated with non-self healing and in vivo and in vitro antigen-specific non-responsiveness. Such antigen-specific unresponsiveness is also observed in visceral leishmaniasis (VL). The non-responsiveness seen in VL disease is believed to be due, in part, to serum-derived factors, including raised serum soluble IL-2 receptor (sIL-2R). Raised sIL-2R in serum was not a consistent feature of DCL in our study (range: 787-4546 U/ml) but was frequently observed in sera of patients with other dermatological disorders (range: 474-3313 U/ml) and some patients with the simple local cutaneous leishmaniasis (LCL; range: 556-4247 U/ml). The level of sIL-2R in the sera of DCL patients was not indicative of the disease state. Sera from DCL patients did not reduce proliferation of the IL-2-dependent CTLL cell line nor reduce PHA-driven mononuclear cell proliferation, although sera from VL patients could. Both DCL and VL sera could reduce the L. aethiopica-driven proliferation. Furthermore addition of serial dilutions of recombinant IL-2 to CTLL cultured in VL or DCL sera containing high sIL-2R levels did not alter the effect of such sera on proliferation. We conclude therefore, that raised sIL-2R in serum is not associated with the immunosuppression in DCL. PMID- 8191227 TI - Does vitamin C alleviate the symptoms of the common cold?--a review of current evidence. AB - Since 1971, 21 placebo-controlled studies have been made to establish whether vitamin C at a dosage of > or = 1 g/day affects the common cold. These studies have not found any consistent evidence that vitamin C supplementation reduces the incidence of the common cold in the general population. Nevertheless, in each of the 21 studies, vitamin C reduced the duration of episodes and the severity of the symptoms of the common cold by an average of 23%. However, there have been large variations in the benefits observed, and clinical significance cannot be clearly inferred from the results. Still, the consistency of the results indicates that the role of vitamin C in the treatment of the common cold should be reconsidered. PMID- 8191228 TI - Salmonella typhi meningitis. AB - Whereas typhoid fever is still an endemic disease in some parts of the world, meningeal involvement in this disease is a rare occurrence. We report a case of Salmonella typhi meningitis in a 70-year-old woman. The patient was treated with ampicillin and the only sequela was right-sided deafness. PMID- 8191229 TI - AIDS presenting as septic shock caused by Mycobacterium tuberculosis. AB - Concurrent with the AIDS epidemic, an increasing incidence of tuberculosis has been noted. In HIV-infected patients with immunodeficiency, atypical forms of tuberculosis are seen. A case of disseminated tuberculosis with septic shock in an elderly patient with previously unknown HIV infection is reported. PMID- 8191230 TI - A case of fulminant ecthyma gangrenosum associated with Pseudomonas aeruginosa infection in a patient with methylmalonic acidemia. AB - A 6-month-old boy with methylmalonic acidemia died of ecthyma gangrenosum caused by systemic Pseudomonas aeruginosa infection. Subtle malnutrition accompanied by the occasional protein restriction treatment may have underlain the development of serious infection in this case. PMID- 8191231 TI - Reversible severe neutropenia after ceftriaxone. AB - A 57-year-old woman developed severe neutropenia during treatment of an upper urinary tract infection with intravenous ceftriaxone. The dosage was 1 g/day for 18 days. There was a return to normal granulopoiesis after the drug was discontinued. PMID- 8191232 TI - Delayed treatment of pulmonary blastomycosis causing vertebral osteomyelitis, paraspinal abscess, and spinal cord compression. AB - A 36-year-old woman with gallbladder disease had an incidental finding of asymptomatic cavitary lung infection with Blastomyces dermatitidis. No treatment was given initially, and 2 months later she presented with vertebral osteomyelitis, paraspinal abscess, and spinal cord compression due to dissemination of the fungus. The patient recovered following surgical debridement and treatment with 1 g of amphotericin B, followed by itraconazole 400 mg QD for 6 months. In spite of previous reports of the self limiting nature of primary pulmonary blastomycosis in the normal host, antifungal therapy may be needed in cases that do not resolve spontaneously within a short period of time, or if transient immunosuppression may be anticipated as may occur following surgery or after acquisition of other infections. PMID- 8191233 TI - Microscopic examination of sperm as the diagnostic clue in a case of Schistosoma haematobium infection. AB - Early diagnosis and treatment of Schistosoma haematobium infections is imperative to prevent chronic manifestations of the disease. Microscopical examination of urine and faeces, and rectal biopsy are widely used standard methods for the rapid diagnosis of schistosomiasis. We report a case in whom numerous Schistosoma haematobium eggs were demonstrated in sperm, even though repeated examination of urine and rectal biopsies had been futile. It is concluded that the case presented demonstrates the importance of using sperm as an alternative sample material when schistosoma eggs are not found in conventional sample materials from male patients suspected of being infected with Schistosoma haematobium. PMID- 8191234 TI - Abdominal lymphonodal enlargement in HIV patients detected by ultrasonography. PMID- 8191235 TI - Substantial decline of notified hepatitis B in major parts of Europe after 1985. AB - A decline in the incidence of notified hepatitis B cases has been observed in major parts of Europe since the mid-1980s. Sweden may be taken as an example of a low prevalence area in the north where notifications of acute hepatitis B declined from 6 cases/100,000 inhabitants in 1985 to only 3/100,000 annually in 1988-91. Choosing W. Germany as an example from central Europe, the notification rate of acute hepatitis B declined from 11 cases/100,000 inhabitants in 1984 to 6 8/100,000 in 1988-91. In Italy, a dramatic decline in hepatitis B infections has occurred since 1985, according to the national hepatitis surveillance system (SEIEVA), from 12 cases/100,000 inhabitants in 1985 to 5/100,000 in 1988-91. A similar trend has also been observed in the USA which seems to be unrelated to vaccination, since only limited vaccination programs have been initiated in high risk groups. Also in Europe, changed sexual and needle-usage practices in risk groups such as drug addicts and male homosexuals have probably contributed to the observed decline. In southern Europe, rapidly improving socio-economic conditions and improved medical precautions against hepatitis B have probably also been important factors. PMID- 8191236 TI - HTLV-I and -II in intravenous drug users from Sweden and Denmark. AB - 693 IVDU (intravenous drug user) sera from Copenhagen, Malmo and Stockholm were tested, 247 retro- and 446 prospectively, for antibodies to human T-lymphotropic virus (HTLV), types I and II, by means of a commercial whole-virus EIA and/or an HTLV-I/-II peptide-based EIA. Positive EIA reactions were checked and typed by electrophoretic immunoblotting, a differential peptide-based EIA and nucleic acid amplification/hybridization with HTLV-I and -II specific primers and probes. 3 (0.7%) of the prospectively tested IVDUs from Malmo, none of 100 from Stockholm and none of 45 from Copenhagen were HTLV-seropositive. The 3 Malmo IVDU cases were a female immigrant from South America, her male native Swedish spouse (both HTLV-I), and a male immigrant Italian heroinist (HTLV-II). We conclude that HTLV was uncommon among intravenous drug users, a sentinel population, in Sweden and Denmark during 1986 and 1989. However, the occurrence of 3 HTLV-positive cases in Malmo 1993 indicates that the situation can change rapidly. PMID- 8191237 TI - HIV infection among seafarers in Denmark. AB - The purpose of this study was to estimate the minimal magnitude of the HIV problem among seafarers in Denmark. The material is based on case records from the 6 medical departments in Denmark that undertake treatment of HIV patients. Retrospectively, all case records of HIV infection among seafarers--and of their sexual contacts--have been identified. 33 seafarers with HIV infection or AIDS were identified; 17 had no other known risk factor than heterosexual contacts in high-endemic areas. These results show that HIV infections have entered into the heterosexual group of seafarers. HIV-infected seafarers are a risk group for carrying HIV infection into the heterosexual population in non-endemic areas. In 5 known cases, this has actually taken place in Denmark. The majority of the heterosexually infected seafarers were probably infected early in the AIDS era. We do not know if Danish seafarers are still acquiring HIV abroad. PMID- 8191238 TI - Seroreactivity to Pneumocystis carinii in patients with AIDS versus other immunosuppressed patients. AB - The aim was to study the humoral response to Pneumocystis carinii and its diagnostic use in patients with P. carinii pneumonia (PCP). The antibody response was measured by indirect immunofluorescence in AIDS patients versus other immunosuppressed patients with 122 episodes of confirmed PCP. During the early acute stage of the pneumonia, anti-P. carinii antibodies were found in 17% of AIDS and 24% of other immunosuppressed patients. In the second serum sample, antibodies were still found in 17% of the AIDS patients but in as many as 56% of the otherwise immunosuppressed patients. Antibodies were also found in 17% of HIV positive and 15% of other immunosuppressed control patients, but only in 3% of immunocompetent controls (p < 0.001). Paired sera were available from 55 patients during 58 PCP episodes. Seroconversion or a fourfold rise in titre was detected in only 1/36 (3%) AIDS patients but in 10/22 (45%), (95% c.i.: 24-66%) other immunosuppressed patients (p < 0.001). We conclude that AIDS patients seem to have lost their ability to develop a humoral response to P. carinii during pneumonia, whereas many other immunosuppressed patients do respond. In these patients the serological test against P. carinii was of no diagnostic value in the acute phase of the infection, whereas when analysing paired sera it was a useful complement to the clinical diagnosis. PMID- 8191239 TI - Clinical significance of neutrophil functional activity in HIV infection. AB - Functional activity of polymorphonuclear neutrophils (PMN) was tested in 63 HIV-1 infected patients. PMN chemiluminescence (CL) and intracellular enzyme activity were both depressed in patients at all stages of infection, though this depression was more pronounced in AIDS patients. We found no such depression when cells were incubated in the presence of autologous serum. PMN phagocytosis in the presence of serum was reduced in the early stage of HIV infection (LAS) but was in the normal range in AIDS patients. No differences in PMN functional activity between patients with LAS and those with dermatological disorders were found. The appearance of recurrent upper respiratory tract infection was associated with reduced PMN CL. The most pronounced changes in PMN activity were observed in patients with severe, recurrent bacterial pneumonia and Pneumocystis carinii pneumonia. A lower level of PMN activity was found in patients with infection progressing rapidly towards AIDS than in patients with a relatively stable course of infection. Thus, PMN CL may be regarded as a predictive factor for the progression of HIV infection. PMID- 8191240 TI - Safety of alternating ganciclovir and foscarnet maintenance therapy in human immunodeficiency virus (HIV)-related cytomegalovirus infections. An open-labeled pilot study. AB - In the treatment of cytomegalovirus (CMV) disease in patients with AIDS, a life long suppression therapy following an induction therapy consisting of ganciclovir or foscarnet is essential. Due to drug-related toxicities, anti-CMV therapy frequently has to be discontinued. To determine whether toxicities and side effects may be reduced with an alternating combination therapy consisting of ganciclovir and foscarnet (ganciclovir: 5 mg/kg every other day; foscarnet: 120 mg/kg every other day), 10 AIDS patients with CMV disease received this maintenance therapy for a median time of 18.5 weeks (5-51 weeks). Side effects were reported from 5 patients (nausea 5, malaise/fatigue 2, penile ulcers 1). Hematological or renal toxicities were mild, 1-week discontinuation of therapy due to neutropenia was necessary in 1 patient. Progression of CMV disease was observed in 3 patients at 2, 6, and 30 weeks of maintenance therapy. Median relapse-free interval for all patients was 105 days. We conclude that combination therapy with ganciclovir and foscarnet can be used safely for induction and maintenance therapy. Therefore, this regimen should be assessed in further trials to evaluate safety, efficacy, and the development of resistance in comparison to ganciclovir or foscarnet monotherapy. PMID- 8191241 TI - Vasoactive intestinal polypeptide (VIP) secretion and refractory diarrhea in patients with AIDS or AIDS-related complex (ARC). AB - Elevated plasma levels of vasoactive intestinal polypeptide (VIP) (as assessed by a radio-immunoassay), were found in 7/11 patients with AIDS or AIDS-related Complex (ARC), evaluated because of prolonged intractable diarrhea with either an infectious (6 cases) or a non-infectious (5 cases) etiology. Six subjects have been treated with the somatostatin analogue octreotide, which gave both a favourable clinical response and a significant reduction in plasma VIP concentrations. Evaluation of plasma VIP levels may provide a pathophysiological basis for explaining the efficacy of octreotide therapy in HIV-infected patients suffering from both infectious and non-infectious refractory diarrhea. PMID- 8191242 TI - Five versus ten days treatment of streptococcal pharyngotonsillitis: a randomized controlled trial comparing cefpodoxime proxetil and phenoxymethyl penicillin. AB - A total of 220 adults and children > 10 years old (mean 29.5 +/- 11.7 years) with pharyngitis/tonsillitis were randomized to receive either cefpodoxime proxetil 100 mg bid for 5 days (n = 113) or phenoxymethyl penicillin, 600 mg tid for 10 days (n = 107). At the end of treatment of the 166 evaluable patients, a satisfactory clinical response was obtained in 85/88 (96.6%) patients treated with cefpodoxime proxetil and in 75/78 (96.1%) treated with phenoxymethyl penicillin. Group A beta-hemolytic streptococci (GABHS) eradication was similar in both groups: 79/82 (96.3%) patients in the cefpodoxime proxetil group and 64/68 (94.1%) patients in the phenoxymethyl penicillin group. At follow-up (20-30 days after the end of treatment) the GABHS eradication persisted in 67/72 (93.1%) patients treated with cefpodoxime proxetil and in 56/61 (91.8%) patients treated with phenoxymethyl penicillin. Significantly better compliance (p < 0.01) was noticed with the cefpodoxime proxetil regimen compared with the phenoxymethyl penicillin regimen, with only 2/110 (2%) poorly compliant patients in the cefpodoxime proxetil group vs 17/104 (16%) in the phenoxymethyl penicillin group. Thus, the shorter duration of therapy, in conjunction with demonstrated clinical and bacteriological efficacy that is equivalent to standard therapy, makes cefpodoxime proxetil an acceptable alternative for the treatment of GABHS pharyngitis/tonsillitis. PMID- 8191243 TI - Sensitivity of 880 blood culture isolates to 24 antibiotics. AB - Blood culture isolates (n = 880) collected during 2.5 years (period I n = 515, July 1988 to December 1989; period II n = 365, January 1992 to December 1992) were analysed with the agar dilution method to ascertain their sensitivity to 24 antibiotics. The susceptibility of bacteria was classified according to MIC values and susceptibility grouping used in the SIR system (sensitive-S, intermediate-I, resistant-R). Comparison of percentage S+I values for the 2 periods revealed no major development of resistance. Co-trimoxazole and some cephalosporins (cefpirom, cefepime and cefotaxime) were active (S+I) against 88 92% of the strains. Imipenem and the combination piperacillin-tazobaclam were active against 95% of the strains. A very large number of strains (98.2 to 98.6%) were inhibited (S+I) by the quinolones tested, ciprofloxacin and ofloxacin. Comparison of the present results with those of our 1980-81 study yielded no evidence of resistance development, except for an increase in betalactamase producing S. aureus strains, from 67% to 85%. PMID- 8191244 TI - Incidence and clinical significance of positive blood cultures in febrile episodes of patients with hematological malignancies. AB - The characteristics of 554 febrile episodes in 126 patients with a hematological malignancy over a 6-year period (1985-90) were reviewed in order to study the current incidence and clinical significance of blood culture positivity. An infection was documented microbiologically in 28% and clinically in 30% of the episodes. Blood cultures were positive in 19% of the febrile episodes. The rate of blood culture positivity was unrelated to the type of hematological malignancy, to neutropenia and to the presence of infection foci. 21% (26/126) of the patients died of sepsis-related causes. Sepsis-related death occurred in 23% of the blood culture positive febrile episodes, with a median survival time of 2 days. Infection prophylaxis did not reduce either the rate of blood culture positivity or the rate of sepsis-related deaths. Thus, the small proportion of febrile episodes whose fever etiology could be established by blood culture represented 'the tip of the iceberg', i.e. rapidly lethal septic infections with a high mortality rate. This fatality could neither be predicted by a search for infection foci nor prevented by infection prophylaxis. PMID- 8191245 TI - Septic arthritis of the knee: a 10-year review and long-term follow-up using a new scoring system. AB - The case records of 64 patients with 65 episodes of infectious gonarthritis during 1979-88 were reviewed regarding epidemiological, clinical and laboratory data of possible relevance to the course and outcome of the disease. Long-term healing results were evaluated by means of a new scoring system 2-11 years after the acute disease in 46 patients. The infection was acquired by inoculation in 37% and by the hematogenous route in 55%. The major risk factors were trauma to the joint and arthrosis. Staphylococcus aureus was the causative agent in 58% and Streptococci in 15%. Treatment consisted of suction irrigation (86%) or intermittent aspiration (5%) combined with systemic antibiotic treatment. At follow-up, the pain and ache scores of the arthritic joint had decreased by 21% and 16% respectively, compared with the scores of the contralateral control joints. Anatomy and motility were reduced by 9% and 8% respectively. Age < 45 was associated with a greater score loss than in older patients. Treatment delayed by > 5 days was associated with increased loss of motility. We estimate that 79% of the patients had excellent or good long-term results following treatment of infectious arthritis of the knee. Evaluation of healing after infectious gonarthritis by use of a scoring system is quite feasible and allows comparison of different treatment regimes with improved accuracy. PMID- 8191246 TI - Klebsiella pneumoniae meningitis: prognostic factors. AB - All 42 cases of Klebsiella pneumoniae meningitis diagnosed between 1981 and 1991 were evaluated. These accounted for 13% of patients with blood and/or cerebrospinal fluid culture-proven bacterial meningitis. There was an increased incidence of K. pneumoniae meningitis from the first 6 years of study (7%) to the last 5 years (16%). K. pneumoniae became increasingly important not only in community-acquired meningitis but also in nosocomial meningitis. 12/13 nosocomial cases were patients who had undergone neurosurgical procedures. The overall mortality rate was 43%. The mortality rate in patients with spontaneous meningitis was higher than that in patients with post-traumatic or postoperative meningitis. Factors that adversely affected mortality were age over 60, diabetes mellitus, and severe neurological deficits on admission. The use of third generation cephalosporins did not reduce the mortality rate. PMID- 8191247 TI - [Malignant melanoma of the head and neck]. AB - The authors evaluate the group of 25 patients suffering from malignant melanoma in head and neck region. Patients were treated on ENT clinic in Hradec Kralove during 1961-1991. The authors describe the localization of malignant melanoma, the process of therapy and the surviving of patients. The contemporary opinions are discussed for possibilities of therapy. PMID- 8191248 TI - [The Ames test in genetic toxicology. II]. AB - The history of Ames test development has been elucidated along with its validity, using new testing strains, means of metabolic activation, new processing techniques and the modality of statistical evaluation of the results. This study summarizes possible applications of Ames test within both experimental and monitoring procedures far beyond the only medical and pharmaceutical field. PMID- 8191249 TI - [Health status in stainless steel welders]. AB - Health state, as well as hematological, biochemical and cytogenetical changes of 53 stainless steel welders were checked-up. Results were compared to those of non exposed persons (control), and to a group of firemen. Urine metals concentrations correlated with the welding fumes density. In the majority of welders typical complaints appeared: aqueous nasal secretion of a clogged nose feeling. Only some of workers suffered from a metal vapours fever. No changes witnessing the above mentioned risk factors influence on the hematological and biochemical findings were ever proved. Cytogenetical analysis confirmed an increased genetic risk. PMID- 8191250 TI - [Evaluation of the quality of a decision-making rule in discriminant analysis]. AB - Logistic regression (LR) and concept of the beta-confidence allocation rule were applied to predict the survival of dogs within the radiobiological experiment. The biochemical and haematological investigations in 86 dogs on the 2nd, 5th and 8th day post-external gamma-neutron irradiation (4.8-7.2 Gy) were used as explanatory variables for the prediction of more than 64 days survival. The influence of experimental conditions was monitored. Correctly predicted cases with LR models were proportioned as 81%, 85% and 93% on 2nd, 5th and 8th day respectively. Using beta-allocation rule, those correctly allocated with 0.50 confidence on the individual days were 75%, 81% and 85% of cases, that adds valuable information on the stability of the estimated classification rule. Method of beta-allocation also allows testing of whether individual observations are correctly assigned at a given significance level. PMID- 8191251 TI - [Treatment of tardive dyskinesias with 7-methoxytacrine. I]. AB - The 7-metoxytacrine (7-MEOTA) is an original Czech cholinergic agent synthetized in the labs of the Military Medical Academy in Hradec Kralove. The treatment of tardive dyskinesias is one of the possible indications of the use of 7-MEOTA in clinical practice. The authors have summed up their experience from the first phase of clinical tests with 7-MEOTA in psychiatrical patients suffering from tardive dyskinesias in long-termed administration of cholinergic agents. The clinical efficiency and tolerance of 7-MEOTA have been evaluated after a single administration of 100 mg of 7-MEOTA per os in 19 patients. A reduction of dyskinesias was observed as early as 4 h following the testing dose. In 5 patients, viz. in 26% a reduction of dyskinesias was observed of more than 50% of the original value of the total score of the testing scale AIMS. Except for a slight decrease of the blood pressure and a mild somnolence in 3 patients no other undesirable effects have been observed. In some patients a slight euphorization effect of 7-MEOTA has been found. PMID- 8191252 TI - [Treatment of tardive dyskinesias with 7-methoxycrine. II]. AB - In an open clinical study the authors have verified the effectivity and tolerance of 7-metoxytacrine cholinergic agent (7-MEOTA) in a total consisting of 14 patients with schizophrenic or schizoaffective psychoses suffering from tardive dyskinesias in long-termed treatment with neuroleptics. In the whole group consisting of 14 patients the seven days' administration of the experimental preparation in a dose of 100-150 mg pro die was evaluated. The 7-MEOTA preparation was administered to 7 patients for 2 weeks. In the seven and fourteen days' administration a favourable effect of 7-MEOTA on tardive dyskinesias was observed. A fast onset of the efficiency as early as in the first days of the treatment was recorded. In final evaluation a minimal reduction of 50% of the intensity of the dyskinesias (using the AIMS scale) in 29% of the patients treated for a fortnight was found. The 7-MEOTA preparation was well tolerated, no undesirable marked side effects being observed. A transient increase of ALT was found in 1 patient only in the 2nd week of the treatment. In experimental treatment the maintenance neuroleptical therapy was not discontinued. An improvement of the dyskinesias overlasted in some patients as long as 2 month g after the discontinuation of the administration of 7-MEOTA preparation. PMID- 8191253 TI - [The Ames test in genetic toxicology. I]. AB - The present study deals with the basic principles of the genetic toxicology, the use of detection methods to determine substances with genotoxic effects and emphasizes the advantage of using tests on prokaryotic-bacterial level. The so called Ames test, i.e. the testing system with Salmonella typhimurium strains, is also detailed. PMID- 8191254 TI - [Cryotherapy in retinopathy of prematurity]. AB - Survey of therapeutical and preventive care of premature babies with retinopathy. We observed the children during 10 years (1982-1991). 144 children were cared for various degree of ROP. This number represents 4.5% of unripe babies hospitalized in the pediatric clinic of Faculty hospital in Hradec Kralove. The kryopexis was carried out as a model of prevention of ROP in 66 children, where the success arose in 74%. PMID- 8191255 TI - [The adverse effects of computer video monitors on their operators]. AB - Probable undesirable influence of visual display terminals to attendance are characterized: electric and electrostatic fields, magnetic field, x-ray and UV radiation. There are described protective arrangements here: terminals of a new construction, prospectively protective filters in front of old terminals. PMID- 8191256 TI - [Non-heart surgical procedures in patients with mechanical valve prostheses. Experience with surgery in 38 patients]. AB - The authors discuss their own experience with noncardiac surgery in continuously Coumarine anticoagulant treated patients with mechanical valvular prostheses. Of 38 patients treated since 1986 were 12 operated under full Coumarine anticoagulant treatment, on eighteen patients were given Heparin preoperatively in a continual infusion, five patients were given an anti-agreggation dose of Heparin and other didn't receive any anticoagulant treatment. According to the authors' opinion it is safer to change the patients before the planned surgical treatment to intravenous Heparin. In case of urgent surgery it is, however, possible to operate also anticoagulant treated patients on. The authors in principle don't recommend K vitamin administration before surgery. Antibiotic prophylaxis before surgery is a matter of course. PMID- 8191257 TI - [Personal experience with management of extracorporeal circulation in patients with asymptomatic carotid arteriosclerosis]. AB - The authors describe in following paper their own group of patients with asymptomatic but hemodynamically significant carotid disease operated under cardiopulmonary bypass on. Current studies recommend the "alpha-stat" regime as the optimal strategy of CPB conduction to ensure intraoperative cerebral protection. This study was done to verify this idea. 284 consecutive patients admitted for elective coronary surgery underwent a non-invasive Doppler scanning of extracranial carotid arteries. Twenty seven patients (10%) had significant carotid disease. All patients underwent coronary surgery as the first procedure. There was no cerebral complication in this group of patients and neurological status of these patients postoperatively was the same as it was preoperatively. This study shows that CPB in patients with hemodynamically significant carotid disease can be achieved without impairment of central nervous system with "alpha stat" regime of perfusion. PMID- 8191258 TI - [The position of the aortic bifurcation in humans]. AB - We followed the position of aorta bifurcation in the arteriograms of 253 persons of known sex and age and in four human foetus. There exists a statistically relevant difference between sex and age. Bifurcation has a higher position in women than in men. In foetus the bifurcation position is placed relatively high- in the 3rd lumbal vertebra--in adults the bifurcation position is in the 4th lumbal vertebra. We can observe a slow decrease of aortal bifurcation to the distal direction in humans after 50 years of age. This descent is statistically significant. PMID- 8191259 TI - Syntactic context effects on word recognition: a developmental study. AB - In the present study, grammatical context effects on word recognition were examined among skilled and less skilled second and sixth grade readers. Of particular interest was how the word decoding ability may correlate with the grammatical context effect. For this purpose the rich case-marking system of the Finnish language was exploited. Recognition latencies for sentence-final nouns were measured as a function of their syntactic agreement with the preceding adjective. The naming and lexical decision tasks were used as critical measures. The study showed a clear syntactic context effect for each of the four experimental groups. The magnitude of the observed syntactic effect was substantially larger compared to earlier results. Furthermore, the effect emerged both in naming and lexical decision. In naming, less skilled 2nd grade decoders were more affected by grammatical incongruency than their more competent peers, whereas in lexical decision the skilled 6th graders differed from other groups by showing a smaller syntactic effect. The results are discussed in the light of Stanovich's interactive-compensatory model of word recognition. PMID- 8191260 TI - Characteristic patterns of verbal memory function in patients with Huntington's disease. AB - Various aspects of verbal memory in patients with Huntington's disease (HD) were studied using the California Verbal Learning Test (CVLT). We tested if the level and interplay between 5 parameters of different memory mechanisms and processes were sufficiently specific to allow acceptable discrimination between patients with HD, patients with Parkinson's disease (PD), and patients without known CNS disease or injury. The HD-patients were characterized by a deficit in acquisition, elevated rates of recall errors and increased use of a passive learning strategy. Preserved aspects were shown in retention over time, interference effects and recognition relative to recall. Employing multivariate classification and validation techniques, the 5 CVLT-features demonstrated good separability between the HD-patients and the control patients. Qualitative similarities between subgroups were suggested, but more disease-specific data seemed necessary in further studies. A number of findings suggested a defect in the active organization of items to be encoded and recalled in HD. Similar findings in the PD-group might indicate that this trait is common in several types of 'subcortical dementia'. PMID- 8191261 TI - Assessment of 'subcortical dementia' in patients with Huntington's disease, Parkinson's disease, multiple sclerosis and AIDS by a neuropsychological screening battery. AB - Four diagnostic groups categorized as 'subcortical dementia' were studied using a neuropsychological screening battery. The specificity of the battery in disclosing characteristic patterns of impairment in subgroups within the category, and the correspondence between natural subgroups generated by an unsupervised statistical classification technique and the diagnostic labels were investigated. All cognitive affected subgroups demonstrated impairment on tests of sensomotor function, cognitive efficiency and/or memory, and were characterized in terms of severity of impairment as well as a progressive involvement of functional areas. The diagnostic groups were not evenly represented in all natural subgroups. Affected AIDS-patients seemed to resemble patients with Huntington's disease more than the other diagnostic groups. The screening battery could give a general characterization of the pattern of 'subcortical dementia' and different levels of impairment, but more specific process-oriented tasks are needed to contrast diagnostic groups within the concept of 'subcortical dementia'. PMID- 8191262 TI - The therapeutic alliance--a conceptual analysis. AB - The role and function of the therapeutic alliance in psychotherapy has increasingly been the focus of clinicians' and researchers' interests over the last decade. Alliance concepts have, however, been criticized for lack of conceptual clarity. The paper presents a generic model as a heuristic means for clarifying the conceptual meaning of the therapeutic alliance. The model distinguishes between the personal relationship aspect, and the collaborative, task-related aspect of the alliance, with therapist, patient, and common contributions to each of these aspects. The model is compared to other alliance conceptualizations, and its implications for alliance theory and research are discussed. A content analysis of four widely used alliance scales in relation to the model shows the scales to represent conceptually different, yet overlapping constructs. It is argued that the componential nature of the therapeutic alliance will render difficult any interpretation of findings regarding the relationship between alliance and outcome in traditional process-outcome research. More complex research strategies guided by theory are called for, if the therapeutic alliance should remain a vital field of research. PMID- 8191263 TI - [Duodenal ulcer disease: a defect in the secretory immune response to Helicobacter pylori?]. AB - In a prospective study we examined 20 Helicobacter pylori (HP)-positive duodenal ulcer patients (5 female, 15 male; age 26-70 [mean 43] years), 20 HP-positive patients with non-ulcer dyspepsia (10 female, 10 male; age 26-79 [mean 48] years) and 10 HP-negative patients with non-ulcer dyspepsia (5 female, 5 male; age 21-76 [mean 45] years) during upper GI-endoscopy. HP was detected by histology (H&E, Giemsa), rapid urease test (CLO) and serology (Cobas Core Anti-H. pylori EIA). IgA anti-HP in gastric juice was determined by ELISA. HP-positivity included positivity in all methods, and HP-negativity failure to detect HP-infection by all methods used. Of the 20 duodenal ulcer patients, 10 patients (2 female, 8 male; age 26-70 [mean 42] years) had an endoscopically documented duodenal ulcer at an earlier endoscopy with no current ulcer, 10 patients had florid duodenal ulcer disease at the time of examination. Duodenal ulcer patients compared with non-ulcer dyspepsia patients were tended to have higher serum IgG anti-HP (551 +/ 240 vs. 338 +/- 159 U/ml) and significantly higher gastric juice IgA anti-HP (50.0 +/- 7.3 vs. 26.5 +/- 4.3 relative units). Concentrations of both serum IgG anti-HP and gastric juice IgA anti-HP tended to be higher in patients with positive ulcer history but no present ulcer compared with patients with florid ulcer disease (934 +/- 456 vs. 170 +/- 63 U/ml and 60.0 +/- 8.6 vs. 40.8 +/- 10.4 relative units).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191264 TI - [Suppression of Helicobacter pylori by local secretory immune response?]. AB - 54 patients (22 females, 32 males, age 21-79, mean 45 years) referred for upper gastrointestinal endoscopy were investigated. Helicobacter pylori (HP) infection was determined using histology (H&E and Giemsa stain), rapid urease test (CLO) and serology (Cobas Core Anti-H. pylori EIA). Density of HP colonization was determined in gastric antral (3 biopsy specimens) and body mucosa (2 biopsy specimens) and semiquantitatively graded on a scale of 0 to 3. Gastric colonization was obtained by addition of the two scores. IgA anti-HP concentration was determined by ELISA using the same FPLC purified HP-antigen mixture as for serology. Gastric juice IgA anti-HP concentration in HP-positive patients (n = 40) was significantly higher than in HP-negative (n = 14) patients (38.3 +/- 4.6 vs. 5.4 +/- 1.2 relative units, p < 0.001). Comparison of HP colonization density of gastric mucosa with gastric juice IgA anti-HP concentration of the 54 patients by binominal regression analysis yielded a correlation coefficient of 0.65 (p < 0.01). The biphasic course of the curve suggests a mutual relationship of HP-colonization density and IgA immune response. Increasing colonization densities seemed to induce increasing secretory immune responses. Half-maximal and higher immune responses, however, seemed to suppress further HP colonization in vivo without eradicating the infection. PMID- 8191265 TI - [Laparoscopic intestinal surgery]. AB - The objective of the present study was to demonstrate the feasibility of laparoscopic bowel surgery. From June 1990 to September 1993 14 small bowel and 15 colon operations were performed laparoscopically in the surgical department of Aarberg Hospital. The results have been analyzed retrospectively. The indication for all small bowel operations was intestinal obstruction. Adhesiolysis, hernia repair and resections were performed either by laparoscopy or by laparoscopically assisted surgery. There were no complications. Laparoscopy therefore has proven to be a good method for treating intestinal obstruction of various origin. 11 colon resections were performed without anastomotic leakage. There were two conversions to laparotomy. Three complications occurred but resolved spontaneously. Two patients died from causes unrelated to the laparoscopic procedure. Our results demonstrate that laparoscopic resections of the colon are feasible. Further evaluation is needed to assess their clinical value. PMID- 8191266 TI - [Cytomegalovirus in liver transplantation: incidence and groups at risk]. AB - Cytomegalovirus (CMV) belongs to the family of Herpes viridae and has become the single most important viral pathogen in clinical transplantation. This is an endemic and ubiquitous virus. After transplantation it is necessary to distinguish CMV infection (positive seroconversion and/or isolation of the virus in the blood, urine, sputum or tissues in the absence of clinical symptoms) from CMV disease, which is a clinical expression of viremia in association with a documented CMV infection. The overall incidence of CMV infection in transplant recipients is about 50% and the incidence of CMV disease ranges from 15 to 25% whatever the transplanted organ. In this study (52 liver transplantations in 48 patients), 12 patients had CMV infection and 10 patients developed CMV disease (24%). The onset of CMV disease was 33 +/- 7 days after transplantation. Cytomegalovirus hepatitis was observed 7 times, CMV pneumonia once and 2 CMV infections characterized by oscillating fever in association with a hematological syndrome. 8 patients were treated with intravenous gancyclovir (DHPG, 9-[1,3 dihydroxy-2-propoxymethyl]-guanine) for 15 days and 2 patients by reduction of their immunosuppressive therapy only. There were significantly more (p < 0.05) opportunistic infections and/or bacteremia in patients with CMV disease. The association of CMV IgG negative recipients and CMV IgG positive donors appeared to be a significant factor (p < 0.05) for CMV disease. The number of transfusions, the level of immunosuppression and the absence of prophylaxis did not influence the incidence of CMV disease. Despite prolonged hospitalization and increased morbidity, there were no deaths in patients who developed CMV disease, which is good evidence of the efficacy of gancyclovir.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191267 TI - [Prevention of viral recurrence following liver transplantation for post hepatitis B and B-delta cirrhosis]. AB - The incidence of recurrence of hepatitis B virus (HBV) following orthotopic liver transplantation (OLT) is as high as 80% when no attempt at prevention has been considered. HBV reinfection is associated with the reappearance of hepatitis B surface antigen (HBsAg) and HBV DNA in serum and, in most cases, with rapid severe graft damage. Immunoprophylaxis using polyclonal anti-HBs immunoglobulins reduces the risk of recurrence but this long-term therapy remains highly expensive. In this report, we use fresh frozen plasma (FFP) with high titers of anti-HBs immunoglobulins in an attempt to reduce HBV recurrence. From July 1987 to September 1993, 11 patients underwent OLT for HBV-related liver disease (18% of our OLT patients). FFP were administered to 6 patients continually for 7 to 46 months. Only one patient, under long-term immunosuppressive treatment before OLT, was reinfected 7 months after OLT. Rapid development of graft failure was observed with histologic manifestations of a fibrosing cholestatic hepatitis, leading to patient death after 12.5 months with concomitant bacterial infection. In this protocol, the rate of reappearance of HBsAg was 17%, a figure which can be favorably compared with other reports. All patients were subsequently tested for HCV and HIV and remained negative. In conclusion, FFP with high titers of anti-HBs immunoglobulins is at least as effective as polyclonal anti-HBs immunoglobulins in reducing the rate of HBV recurrence following OLT. The estimated cost of this new immunoprophylaxis method is less than 10% of the classical prophylaxis based on purified human polyclonal anti-HBs immunoglobulins. PMID- 8191268 TI - [Dilatation of the common bile duct: what does endoscopic sonography contribute?]. AB - In a prospective study 20 patients (14 women, 6 men; mean age 62 [31-81] years) with extrahepatic obstructive jaundice (n = 15) or common bile duct dilatation (CBD) without cholestasis (n = 5) were investigated by endoscopic ultrasound (EUS). All these patients underwent negative transabdominal ultrasonography (US) (n = 20) and computed tomography (CT) (n = 16). Inclusion criterion was a dilatation of the CBD of > 7 mm or > 10 mm in patients with previous cholecystectomy. The definitive diagnosis of a tumor (n = 8), choledocholithiasis (n = 7), stone migration (n = 1), choledochocele (n = 2) or slight dilatation of the CBD without obstruction (n = 2) was confirmed by endoscopic retrograde cholangiopancreatography (ERCP) (n = 13), percutaneous transhepatic cholangiography (PTC) (n = 2), intraoperative cholangiography (n = 1) and follow up (n = 4; mean 21 [3-36] mo.). Dilatation of the CBD could be demonstrated in all cases by EUS. Common bile duct stones (2-15 mm) were demonstrated by EUS in every case. CBD dilatation without underlying obstruction was correctly identified by EUS in all patients and confirmed by further clinical and laboratory findings as well as EUS and ERCP (n = 1). EUS correctly described the localization of a malignant obstruction (n = 8) as confirmed by ERCP/PTC. All tumors (pancreatic head carcinoma n = 3, periampullary tumor (n = 5) could be visualized by EUS. The diagnosis was confirmed by surgery (n = 5) or ultrasound guided fine needle puncture (FNP) after a bile duct prosthesis had been placed (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191269 TI - [Pruritus associated with liver disease: propofol, a new therapeutic approach?]. AB - Pruritus is a severe and troublesome symptom in patients with cholestasis and is often difficult to treat. Propofol was recently shown to be efficient in the treatment of pruritus secondary to spinal morphine administration. In a prospective, randomized, double-blind, cross-over and placebo controlled study, 20 patients received 1 dose of propofol (15 mg) and 1 dose of Intralipid (1.5 mg) during a 2-day study period. Pruritus was assessed by a visual analogue scale from 0 (no pruritus) to 10 (most severe pruritus imaginable). Treatment success was defined as a decrease in pruritus of at least 4 points on the scale in 80% of the patients receiving propofol and in 15% of those receiving intralipid (p < 0.05). Discomfort on injection was observed in 15% under propofol treatment. In conclusion this study shows that subhypnotic doses of propofol are effective for the short-term symptomatic relief of pruritus associated with liver disease. At the dose administered, side effects were rare and minor. PMID- 8191271 TI - [Percutaneous endoscopic gastrostomy in long-term nutrition]. AB - Percutaneous endoscopic gastrostomy is the preferred method for administration of long-term enteral tube feeding. Data on long-term follow-ups are rare. We report the long-term outcome and the complication rates after percutaneous endoscopic gastrostomy in 165 patients (mean age 70 years). The most common indications were neurologically-related swallowing disorders. The data were collected prospectively. Percutaneous endoscopic gastrostomy in patients was technically successful in 164 patients (99%), with a mean implantation time of 12 minutes. The procedure-related morbidity was 1.2%. The mean length of percutaneous endoscopic gastrostomy feeding was 26 weeks (1-98) for the Charriere 9-tube and 29 weeks (1-158) for Charriere 15-tubes. There were 12% tube-related and 15% feeding-related late complications, the main ones being local skin infections (7.3%) and gastric perforations (1.2%). The procedure-related mortality was 0.6%. We conclude that endoscopically assisted percutaneous gastrostomy is the procedure of choice for long-term enteral nutrition in patients requiring tube feeding. PMID- 8191270 TI - [Sulindac in familial adenomatous polyposis coli--preliminary findings of a prospective study]. AB - Several authors have reported regression of rectal polyps after administration of sulindac in patients with familial adenomatous polyposis (FAP) and subtotal colectomy. However, only a few reports have been published about the effect of sulindac in the intact colon of FAP-patients. 12 patients (FAP n = 10, Lynch-I syndrome n = 1, juvenile polyposis n = 1/patient with intact colon n = 6, ileorectal anastomosis n = 4, right-sided hemicolectomy n = 2) have been treated with sulindac (3 x 100 mg/d orally) for 4 months. In all patients colonoscopy (if postcolectomy, rectoscopy) with videotape documentation was performed before and after sulindac therapy. Some polyps were excised for histology. In 11/12 patients a regression of the number and size of polyps occurred. In addition, in patients with intact colon no polyps were observed proximal to the sigmoid colon. In one patient sulindac had to be discontinued after 4 weeks' course because of abdominal pain. A control colonoscopy revealed only slight reduction in polyps. In 3/12 patients no polyps remained after sulindac. In a further 3/12 patients with initial tubulous adenomatous polyps, only microadenomas were observed after treatment. We therefore conclude that sulindac is effective in FAP-patients (and very probably in other hereditary polyposis syndromes) with intact colon as well as after (hemi-)colectomy in reducing the number and size of polyps. Long term studies are needed to clarify the optimal dosage, treatment time period, and long term potential for development of carcinoma under sulindac treatment. PMID- 8191272 TI - Dehydrogenase activity of the microbial biomass in soils from a field experiment amended with heavy metal contaminated sewage sludges. AB - Dehydrogenase activity (DHA) of the microbial biomass was measured in sewage sludge amended soil samples collected from the Braunschweig experimental site, Germany. The site had received additions of sludge with or without heavy metals at two application rates (100 m3/ha per year and 300 m3/ha per year) on soils of 'low' (4.8-5.8) and 'high' (5.4-7.0) pH since 1980. DHA was found to be a sensitive and precise assay for determining the effect of heavy metals on substrate-induced (glucose) microbial biomass in sewage sludge amended soils. Effects on DHA were determined in relation to heavy metal concentrations and other soil factors. Addition of relatively uncontaminated sludge enhanced DHA, but this was dependent on the level and type of sludge addition. Adverse metal effects were only significant in the most contaminated soils where sludge had been added to the 'high' and 'low' pH treatments at Braunschweig. However, these effects were small compared to the effects of high rates of sludge addition alone, despite exceeding statutory limits for Zn and Cu, where concentrations reached 341 and 99 micrograms/g, respectively. PMID- 8191273 TI - Toxin extraction from an Anabaenopsis milleri--dominated bloom. AB - This paper reports the presence of microcystin type toxins in extracts of a natural bloom of cyanobacteria composed predominantly of Anabaenopsis milleri Woronichin. The toxins have been extracted, purified and compared to microcystin LR. The LD50 of A. milleri bloom material was 600-1500 mg lyophilized cells/kg body weight. Symptoms and pathological signs of poisoning in mice were characteristic of cyanobacterial hepatotoxins, with enlarged darkened livers with weights of 8-10% of the total body weight. Thin-layer chromatography of the extract resulted in one toxic band, which was separated from pigments and 280-nm absorbing compounds. The toxic fraction was further separated using reversed phase high performance liquid chromatography and one toxic band was recovered. This fraction yielded a single, toxic peak with a retention time of 11.3 min after high performance liquid chromatography. The absorption spectrum of the purified toxin had a maximum at 238-240 nm and was characteristic of cyanobacterial hepatotoxic peptides. Comparison of the chromatographic behaviour of the purified toxin with microcystin-LR on reversed phase and on internal surface reversed phase, high performance liquid chromatography indicated that an A. milleri bloom material toxin was a microcystin type toxin and it is highly likely that the purified toxin is microcystin-LR. PMID- 8191274 TI - Radiation doses in Pakistani houses. AB - Natural radioactivity in building materials has been measured to determine the external dose equivalent rate due to walls, floor and ceiling. Indoor radon has been measured to estimate the internal dose rate. Occupancy factor was estimated to be 0.3. It is found that the external dose equivalent rate to lungs is less than or equal to the internal dose equivalent rate. Both the external and internal dose equivalent rates in the houses under consideration are less than the background dose equivalent rate value given by UNSCEAR. PMID- 8191275 TI - Evidence that mercury from silver dental fillings may be an etiological factor in multiple sclerosis. AB - This paper investigates the hypothesis that mercury from silver dental fillings (amalgam) may be related to multiple sclerosis (MS). It compares blood findings between MS subjects who had their amalgams removed to MS subjects with amalgams. MS subjects with amalgams were found to have significantly lower levels of red blood cells, hemoglobin and hematocrit compared to MS subjects with amalgam removal. Thyroxine levels were also significantly lower in the MS amalgam group and they had significantly lower levels of total T Lymphocytes and T-8 (CD8) suppressor cells. The MS amalgam group had significantly higher blood urea nitrogen and lower serum IgG. Hair mercury was significantly higher in the MS subjects compared to the non-MS control group. A health questionnaire found that MS subjects with amalgams had significantly more (33.7%) exacerbations during the past 12 months compared to the MS volunteers with amalgam removal. The paper also examines epidemiological correlations between dental caries and MS; as well as how mercury could be causing the pathological and physiological changes found in multiple sclerosis. PMID- 8191276 TI - Radon risk estimates. PMID- 8191277 TI - England's oldest human bone steps out. PMID- 8191278 TI - Molecular evolution. Archaea and eukaryotes grow closer. PMID- 8191279 TI - Switzerland has its own blood scandal. PMID- 8191280 TI - Storm clouds over Russian science. PMID- 8191281 TI - Biology. Elite groups struggle on with a little help from the west. PMID- 8191282 TI - Antibody catalyzed cationic cyclization. AB - Two major goals for the design of new catalysts are the facilitation of chemical transformations and control of product outcome. An antibody has been induced that efficiently catalyzes a cationic cyclization in which an acyclic olefinic sulfonate ester substrate is converted almost exclusively (98 percent) to a cyclic alcohol. The key to the catalysis of the reaction and the restriction of the product complexity is the use of antibody binding energy to rigidly enforce a concerted mechanism in accord with the design of the hapten. Thus, the ability to direct binding energy allows the experimenter to dictate a reaction mechanism which is an otherwise difficult task in chemistry. New catalysts for cationic cyclization may be of general use in the formation of carbon-carbon and carbon heteroatom bonds leading to multi-ring molecules including steroids and heterocyclic compounds. PMID- 8191283 TI - Mechanism of catalytic oxygenation of alkanes by halogenated iron porphyrins. AB - Halogenation of an iron porphyrin causes severe saddling of the macrocyclic structure and a large positive shift in the iron(III)/(II) redox couple. Although pre-halogenated iron(II) porphyrins such as Fe(TFPPBr8) [H2TFPPBr8, beta octabromo-tetrakis(pentafluorophenyl)-porphyrin] are relatively resistant to autoxidation, they rapidly reduce alkyl hydroperoxides. These and related reactivity studies suggest that catalysis of alkane oxygenation by Fe(TFPPBr8)Cl occurs through a radical-chain mechanism in which the radicals are generated by oxidation and reduction of alkyl hydroperoxides. PMID- 8191284 TI - Geographic variation of p53 mutational profile in nonmalignant human liver. AB - Fifty-eight percent of hepatocellular carcinomas (HCCs) from Qidong, China, contain an AGG to AGT mutation at codon 249 of the p53 tumor suppressor gene, a mutation that is rarely seen in HCCs from Western countries. The population of Qidong is exposed to high levels of aflatoxin B1 (AFB1), a fungal toxin that has been shown to induce the same mutation in cultured human HCC cells. To investigate the role of AFB1 and of these p53 mutations in hepatocarcinogenesis, normal liver samples from the United States, Thailand, and Qidong (where AFB1 exposures are negligible, low and high, respectively) were examined for p53 mutations. The frequency of the AGG to AGT mutation at codon 249 paralleled the level of AFB1 exposure, which supports the hypothesis that this toxin has a causative--and probably early--role in hepatocarcinogenesis. PMID- 8191285 TI - Prevention of lipopolysaccharide-induced lethal toxicity by tyrosine kinase inhibitors. AB - Septic shock results from excessive stimulation of the host immune system, especially macrophages, by lipopolysaccharide (LPS), or endotoxin, which resides on the outer membrane of bacteria. Protein tyrosine kinase inhibitors of the tyrphostin AG 126 family protect mice against LPS-induced lethal toxicity. The protection correlates with the ability of these agents to block LPS-induced production of tumor necrosis factor alpha (TNF-alpha) and nitric oxide in macrophages as well as LPS-induced production of TNF-alpha in vivo. Furthermore, this inhibitory effect correlated with the potency of AG 126 to block LPS-induced tyrosine phosphorylation of a p42MAPK protein substrate in the murine macrophage. PMID- 8191286 TI - Interaction of MHC class I molecules with the transporter associated with antigen processing. AB - The transporter associated with antigen processing (TAP) delivers cytosolic peptides into the endoplasmic reticulum (ER) where they bind to nascent class 1 histocompatibility molecules. Class 1-peptide complexes are then displayed at the cell surface for recognition by cytotoxic T lymphocytes. Immunoprecipitation of either TAP or class 1 molecules revealed an association between the transporter and diverse class 1 products. TAP bound preferentially to heterodimers of the class 1 heavy chain and beta 2-microglobulin, and the complex subsequently dissociated in parallel with transport of class 1 molecules from the ER to the Golgi apparatus. The TAP-class 1 complexes could also be dissociated in vitro by the addition of class 1-binding peptides. The association of class 1 molecules with TAP likely promotes efficient capture of peptides before their exposure to the lumen of the ER. PMID- 8191287 TI - The TATA-binding protein: a general transcription factor in eukaryotes and archaebacteria. AB - The TATA-binding protein TBP appears to be essential for all transcription in eukaryotic cell nuclei, which suggests that its function was established early in evolution. Archaebacteria constitute a kingdom of organisms distinct from eukaryotes and eubacteria. Archaebacterial gene regulatory sequences often map to TATA box-like motifs. Here it is shown that the archaebacterium Pyrococcus woesei expresses a protein with structural and functional similarity to eukaryotic TBP molecules. This suggests that TBP's role in transcription was established before the archaebacterial and eukaryotic lineages diverged and that the transcription systems of archaebacteria and eukaryotes are fundamentally homologous. PMID- 8191288 TI - Candidate gene associated with a mutation causing recessive polycystic kidney disease in mice. AB - A line of transgenic mice was generated that contains an insertional mutation causing a phenotype similar to human autosomal recessive polycystic kidney disease. Homozygotes displayed a complex phenotype that included bilateral polycystic kidneys and an unusual liver lesion. The mutant locus was cloned and characterized through use of the transgene as a molecular marker. Additionally, a candidate polycystic kidney disease (PKD) gene was identified whose structure and expression are directly associated with the mutant locus. A complementary DNA derived from this gene predicted a peptide containing a motif that was originally identified in several genes involved in cell cycle control. PMID- 8191289 TI - Summation and division by neurons in primate visual cortex. AB - Recordings from monkey primary visual cortex (V1) were used to test a model for the visually driven responses of simple cells. According to the model, simple cells compute a linear sum of the responses of lateral geniculate nucleus (LGN) neurons. In addition, each simple cell's linear response is divided by the pooled activity of a large number of other simple cells. The cell membrane performs both operations; synaptic currents are summed and then divided by the total membrane conductance. Current and conductance are decoupled (by a complementary arrangement of excitation and inhibition) so that current depends only on the LGN inputs and conductance depends only on the cortical inputs. Closed form expressions were derived for fitting and interpreting physiological data. The model accurately predicted responses to drifting grating stimuli of various contrasts, orientations, and spatiotemporal frequencies. PMID- 8191290 TI - An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. AB - Normal processing of the amyloid beta protein precursor (beta APP) results in secretion of a soluble 4-kilodalton protein essentially identical to the amyloid beta protein (A beta) that forms insoluble fibrillar deposits in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing wild-type beta APP or the beta APP717 mutants linked to familial Alzheimer's disease were compared by (i) isolation of metabolically labeled 4-kilodalton A beta from conditioned medium, digestion with cyanogen bromide, and analysis of the carboxyl-terminal peptides released, or (ii) analysis of the A beta in conditioned medium with sandwich enzyme-linked immunosorbent assays that discriminate A beta 1-40 from the longer A beta 1-42. Both methods demonstrated that the 4-kilodalton A beta released from wild-type beta APP is primarily but not exclusively A beta 1-40. The beta APP717 mutations, which are located three residues carboxyl to A beta 43, consistently caused a 1.5- to 1.9-fold increase in the percentage of longer A beta generated. Long A beta (for example, A beta 1 42) forms insoluble amyloid fibrils more rapidly than A beta 1-40. Thus, the beta APP717 mutants may cause Alzheimer's disease because they secrete increased amounts of long A beta, thereby fostering amyloid deposition. PMID- 8191291 TI - Rotatory palmar subluxation of the lunate in post-traumatic ulnar carpal translocation. AB - Post-traumatic ulnar carpal translocation is a rare, severe ligamentous injury to the wrist. Radiologic findings include widening of the radiocarpal joint space at the radial styloid process and ulnar displacement of the carpus. Less than 50% of the lunate articulates with the radius in the neutral position; the lunate is tilted dorsally with palmar subluxation due to a ruptured radio-scapholunate (RSL) ligament. This malposition should be called rotatory palmar subluxation of the lunate (RPSL), by analogy to rotatory subluxation of the scaphoid (RSS). In contrast to dorsiflexed intercalated segment instability (DISI), in RPSL the RSL ligament is ruptured and, in the majority of cases, the scapholunate ligament remains intact. A prompt diagnosis should lead to successful treatment. PMID- 8191292 TI - Fluid-fluid levels in cavernous hemangioma of soft tissue. AB - Five cases of cavernous hemangioma with fluid-fluid levels on magnetic resonance imaging and/or computed tomography are reported. The signal characteristics were those of blood and histological analysis of the fluid-fluid levels showed that they were blood-filled cavities in the tumor. Although this finding itself is not specific, it may help in confirming the diagnosis of cavernous hemangioma. PMID- 8191293 TI - Standards for ultrasonographic measurements of the hip joint in Indian adults. AB - Synovitis in the hip joint, in contrast to that in other limb joints, is extremely difficult to evaluate clinically. In the hip joint synovitis manifests as an increase in the distance between the iliofemoral ligament and the femoral neck. The present ultrasonographic study was undertaken in 110 healthy Indian adults to establish standards for the depth of the normal hip joint space in the normal Indian adult population. The shortest distance was 4 mm, the longest was 9 mm. The mean distance was 6.4 (S.D. 1.1) mm. The mean difference between the right and left hips was 0.42 (S.D. 0.49) mm. An age-specific reference curve with 95% confidence limits was constructed. No correlation was found between hip joint space and the subjects' height, weight, age or sex. It is concluded that a distance between the iliofemoral ligament and the femoral neck of more than 9 mm or a difference in measurement between the hips of 1 mm or more suggests an intracapsular effusion or active synovitis. These figures are at variance with the measurements obtained in studies on Western white populations. PMID- 8191294 TI - Isolated or dominant lesions of the patella in gout: a report of seven patients. AB - Isolated or dominant osteolytic lesions of the patella are an unusual manifestation of gout. We present seven patients who had such patellar lesions unilaterally (six patients) or bilaterally (one patient) and analyze the radiologic characteristics to determine whether they can be differentiated from those of other osteolytic lesions of the patella. The lesions were uniformly characterized by a geographic pattern of bone destruction in the superolateral aspect of the patella. Five lesions were each accompanied by a peripatellar soft tissue mass, four of which contained calcification. It therefore appears that an osteolytic lesion of the superolateral portion of the patella, especially when associated with a peripatellar calcified soft tissue mass, should alert one to the possible diagnosis of gout. Awareness of this possibility may obviate the need for invasive diagnostic procedures. PMID- 8191295 TI - Coraco-clavicular joint: normal variant in humans. A radiographic demonstration in the human and non-human primate. AB - The coraco-clavicular joint is a true synovial joint that may become painful in some patients after trauma. Among the descriptions of this entity is the assertion that the coraco-clavicular joint is routinely seen in gorillas and gibbons. We undertook to assess the incidence of this variant among gorillas, gibbons, and other non-human primates. All available radiographs of large primates performed at the International Wildlife Conservation Park/Bronx Zoo (IWCP) over the past 10 years were reviewed by a musculoskeletal radiologist (human radiology). All radiographs were taken during the normal clinical care of the non-human primate population of the IWCP and are a part of each animal's clinical record. Eighty-one non-human primate radiographs were suitable for study as they contained the region of interest. The 81 radiographic examinations included 14 different species of non-human primates. The coraco-clavicular joint was seen in 4 out of 9 silver-leaf langur, 2 out of 8 lowland gorilla, and in 1 out of 6 white-handed gibbon. In all non-human primate cases where the coraco clavicular joint occurred, it was bilateral. In 1 out of 8 mandrill, there were very wide distal clavicular ends that articulated both with the coracoid and with the acromion. The coraco-clavicular joint differs from an ossified coraco clavicular ligament. The radiographic appearance is characteristic and is found in both humans and some non-human primate species. It may rarely become painful following trauma. When symptomatic in humans, resection of this anomalous articulation is curative. PMID- 8191296 TI - MR appearance of skeletal neoplasms following cryotherapy. AB - Cryotherapy is an increasingly popular mode of therapy adjunctive to surgical curettage in the treatment of certain skeletal neoplasms, such as giant cell tumors or chondrosarcomas. The magnetic resonance (MR) findings following cryotherapy have not been previously reported. We reviewed the MR findings in seven patients with skeletal neoplasms following curettage and cryotherapy. In six cases we found a zone of varying thickness extending beyond the surgical margins, corresponding to an area of cryoinjury to medullary bone. This zone displayed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, consistent with the presence of marrow edema. This zone of edema almost certainly reflects underlying thermal osteonecrosis. This zone may vary in size and intensity over time as the area of cryoinjury evolves or resolves. MR is currently the imaging procedure of choice for follow-up of most musculoskeletal neoplasms. Knowledge of the MR findings following cryotherapy should help prevent confusion during the interpretation of follow-up MR examinations. PMID- 8191297 TI - Ossification of the Achilles tendon: imaging abnormalities in 12 patients. AB - Ossification of the Achilles tendon is a rare clinical entity that is characterized by the presence of an ossific mass contained within the fibrocartilaginous substance of the tendon. Because the radiographic features of this condition have not been documented entirely and the magnetic resonance (MR) imaging findings have not been determined, a review of 16 affected tendons in 12 patients was performed in an attempt to characterize the imaging abnormalities associated with this process. MR imaging was performed in three Achilles tendons which demonstrated thickening of the tendons at the level of the ossifications and a lack of intratendinous signal abnormalities compatible with acute tendinitis. Signal intensity similar to that of bone marrow was present in the ossifications. PMID- 8191298 TI - Direct ultrasonographic measurement of femoral anteversion in newborns. AB - A direct method of ultrasonographic measurement of the anteversion angle of the femoral neck is presented. Normal values based on measurements in 30 random newborns with vertex presentation correspond well with figures from previous autopsy series. The femoral anteversion in breech presentation was found to be on average 10 degrees greater than in vertex presentation (p < 0.0001). PMID- 8191299 TI - Case report 813: Hibernoma of the left thigh. AB - The MRI features of a hibernoma have been described, as no previous report of MRI findings was found in the literature. The hibernoma presents as a well-delineated soft tissue mass with tissue attenuation intermediate between that of skeletal muscle and subcutaneous fat. Marked contrast enhancement is noted. PMID- 8191300 TI - Case report 826: Physiological resorption of allograft simulating recurrent giant cell tumor. AB - A case of focal resorption in a limb salvage/bone allograft is presented, illustrating that roentgenological differentiation from other causes for graft resorption may be very difficult. The possibilities of infection and tumor recurrence, as well as "physiologic" graft resorption, must be considered in the differential diagnosis of a lytic process in an allograft for limb salvage. To date, early biopsy remains mandatory for accurate diagnosis. PMID- 8191301 TI - Case report 827: Miliary osteosarcomatosis. AB - We presented the case of a 26-year-old woman with a blastic, miliary form of osteosarcomatosis involving the axial skeleton, skull, and long bones to the elbow and knee joint regions who subsequently developed hypocalcemic tetany. Radiologically the lesions mimicked the spread of breast carcinoma, and because of the distribution of the lesions we surmised that the spread was by means of Batson's vertebral plexus of veins. The literature on multiple osteosarcomas was reviewed and an updated clinical subclassification of patients with multiple skeletal osteosarcomas presented. PMID- 8191302 TI - Case report 828: Plexiform neurofibroma of the tibial nerve invading the medial and lateral gastrocnemius muscles and plantaris muscle. AB - A 5-year-old boy presented with a several-year history of swelling of his calf and muscular weakness. MRI demonstrated abnormal signal and diffuse enlargement of the gastrocnemius muscle. Pathological examination revealed plexiform neurofibroma, and the diagnosis of neurofibromatosis was subsequently made. The manifestations of neurofibromatosis and the peripheral nerve sheath tumors encountered in this disease are discussed. Special attention is paid to the MR features of the plexiform neurofibroma which is characteristic of this disorder. PMID- 8191303 TI - Case report 829: Intramuscular myxoid chondrosarcoma. AB - A 61-year-old man presented with a 6-month history of a painless mass in the right buttock. Although the MR appearance of myxoid neoplasms is variable, a myxoid neoplasm was suspected on the basis of the MR study. Percutaneous needle biopsy results yielded a diagnosis of intramuscular myxoma. Myxoid chondrosarcoma, however, was diagnosed at the time of excisional biopsy. One should be wary of a diagnosis of intramuscular myxoma based solely on the results of percutaneous needle biopsy. In addition, myxoid chondrosarcoma of the soft tissues can have a variable appearance on T1-weighted imaging. PMID- 8191304 TI - Case report 830: Aneurysmal bone cyst. PMID- 8191305 TI - Case report 831: Juxta-articular osteoid osteoma. PMID- 8191306 TI - Avulsion fractures of the pelvis in children: a report of 32 fractures and their outcome. AB - Avulsion injuries of the apophyses of the pelvis are mainly athletic injuries and are usually seen in adolescents. In a series of 80 pelvic fractures in children seen and managed in The Royal Liverpool Children's Hospital, Alder Hey, in the last 10 years, 32 avulsion fractures in 25 patients were diagnosed and treated. Twenty-two of these patients were followed for an average of 44 months (range 4 120 months). Eight (33%) were girls, a higher proportion than in other published series. The average age of the children was 13.8 years. These fractures, though generally regarded as trivial injuries, have left disability persisting into adult life, with limitation of sporting ability in 10 of the 22 patients and persistent symptoms in 6, mostly in those with ischial avulsion injuries. Fourteen patients with acute injuries needed hospitalisation, with an average stay of 5 days. The other 11 were suffering from chronic traction injuries sustained in sport. This distinction between acute and chronic injuries has not been emphasized in the other reviews. The radiological appearances, diagnostic problems and morbidity are discussed in order to increase awareness of these injuries. PMID- 8191307 TI - Role of technetium-99m planar bone scanning in the evaluation of low back pain. AB - The records of 1018 patients with low back pain in a tertiary spine referral practice were reviewed. One hundred thirty-nine out of 1018 (13.6%) underwent technetium-99m planar bone scanning as part of their investigation. Seventy-three out of 139 scans (52%) showed increased uptake in some area, but only 27 out of 139 (19.4%) showed increased uptake specifically in the low back. Scans consistently yielded no findings with reference to the back when the prescan diagnosis was spinal stenosis, lumbar pain syndrome, herniated nucleus pulposus, or postlaminectomy syndrome. Some scans gave positive findings in patients with a diagnosis of degenerative disc disease, pseudarthrosis, spondylolisthesis, fracture, infection, metabolic disorder, or tumor. Positive scans were generally obtained early after presentation (within 3 months) and negative scans obtained later (after 6 months), suggesting that clinical suspicion is still the main indication for early scanning. Planar bone scanning was helpful in both diagnosis and therapeutic decision-making in many conditions. PMID- 8191308 TI - Synovial chondromatosis simulating neoplastic degeneration of osteochondroma: findings on MRI and CT. AB - A case is presented of synovial chondromatosis within a bursal sac overlying an osteochondroma in a patient with osteochondromatosis. This condition presented with a symptomatic soft tissue mass containing calcified bodies. It can be mistaken clinically and radiographically for malignant degeneration of an osteochondroma with development of chondrosarcoma. Magnetic resonance findings have not previously been described in this entity and proved helpful in the preoperative diagnosis. Magnetic resonance imaging was also helpful in defining the extent of the lesion. Ultrasound and other imaging modalities are also discussed, including the pathologic basis for the radiographic findings. PMID- 8191309 TI - Are ACE inhibitors equal in congestive heart failure? PMID- 8191310 TI - Relevance of pharmacokinetic differences between ACE inhibitors and their role in the treatment of hypertension. PMID- 8191311 TI - Schools against AIDS project--for the future of our teenagers. PMID- 8191312 TI - Selective posterior rhizotomy in the treatment of spasticity. PMID- 8191313 TI - Prevention of congenital syphilis by effective maternal screening at antenatal clinics. PMID- 8191314 TI - Some reasons for the failure to notify congenital syphilis. PMID- 8191315 TI - Towards a future policy for transplantation in South Africa. PMID- 8191316 TI - Time to abolish the straitjacket. PMID- 8191317 TI - Guidelines for the management of diabetes mellitus--is there a need for consensus? PMID- 8191318 TI - Cholesterol testing--time to change? PMID- 8191319 TI - The neuroleptic malignant syndrome--still a conundrum. PMID- 8191320 TI - Healthy cities for a future South Africa. PMID- 8191321 TI - Compensation for Occupational Injuries and Diseases Bill, 1993. PMID- 8191322 TI - Congenital syphilis as a notifiable disease. AB - A review of the notification of congenital syphilis at Johannesburg Hospital from 1 May 1991 to 30 April 1992 was conducted to evaluate the effect of the recently introduced notification programme. A total of 209 Wassermann reaction (WR) positive mothers were delivered during this time; 12 pregnancies (5.7%) resulted in stillbirths and 8 (3.8%) in incomplete abortions, and there were 2 (0.96%) early neonatal deaths. Only 45 (21.5%) of this group of WR-positive mothers had received antenatal care, and of these 9 (20%) had had adequately documented treatment. There were thus 200 potentially notifiable cases of congenital syphilis according to the Centers for Disease Control classification, of which 24 (12.0%) were actually notified. The goals of the notification programme, namely to increase awareness of congenital syphilis among health care providers and to evaluate the extent of the problem accurately, are clearly not being met. PMID- 8191323 TI - On-site screening for maternal syphilis in an antenatal clinic. AB - STUDY OBJECTIVE: To determine the sensitivity, specificity, negative predictive value and positive predictive value of the rapid plasma reagin (RPR) test as performed on site in an antenatal clinic to facilitate immediate diagnosis and treatment of maternal syphilis. DESIGN: Open, descriptive study. SETTING: Antenatal clinic, Kalafong Hospital, Pretoria. PATIENTS: One thousand two hundred and thirty-seven pregnant patients attending an antenatal clinic for the first time were entered into the study. METHODS: An RPR test was performed on site in the antenatal clinic and by the reference laboratory where a Treponema pallidum haemagglutination test was also performed. MEASUREMENTS AND RESULTS: The results of the RPR test were compared with results reported by the laboratory for sensitivity, specificity, negative and positive predictive values. The RPR test performed on site had a sensitivity of 92.8%, a negative predictive value of 99.5%, a specificity of 96.3%, and a positive predictive value of 64.7%. CONCLUSION: Maternal syphilis can be diagnosed in the majority of cases during the first visit to an antenatal clinic. PMID- 8191324 TI - Re-screening for syphilis at the time of delivery in areas of high prevalence. AB - Two hundred women who were screened for syphilis at their initial antenatal visit were rescreened at the time of delivery. Umbilical cord blood specimens as well as maternal sera were tested. Twenty-two (11%) women were rapid plasma reagin (RPR)-positive at booking, while a total of 23 (12%) were RPR-positive at the time of delivery, including an additional 5 (3%) who seroconverted. Four women who were RPR-positive at initial testing had become negative by the time of delivery following treatment. Of all neonates born to seropositive women, only 1 demonstrated clinical evidence of congenital syphilis. In view of the high seroconversion rate, we recommend screening for syphilis at the initial antenatal visit and rescreening at the time of delivery in areas such as ours. PMID- 8191325 TI - Vaginal yeast infections in diabetic women. AB - Two hundred and three diabetic women (89 with and 114 without genital symptoms) were examined for the presence of yeasts and Trichomonas vaginalis. Yeasts were isolated from the vaginas of 35.5% of patients and were more common in the symptomatic group (48.0%) than the asymptomatic group (25.4%; P < 0.05). Candida albicans was isolated from 12.8% of all patients and showed a significant association with pruritus vulvae (P < 0.05). A significant association was also shown between the presence of yeasts in the rectum and in the vagina. C. glabrata (Torulopsis glabrata) was the commonest yeast species isolated (50.0%), with C. albicans the next most frequent (36.1%). T. vaginalis infection was present in 14.3% of all subjects. PMID- 8191326 TI - Recalcitrant vulvodynia. A clinicopathological study. AB - This study is an analysis of 26 women with burning vulva syndrome. They seldom had frankly abnormal physical findings, and application of acetic acid and colposcopically directed biopsy are therefore mandatory. Histopathological study showed characteristic features of human papillomavirus (HPV) in 20 patients (77%). HPV has been shown to be a cause of vulvar vestibulitis syndrome and was an associated problem in 3 of the 5 patients who had essential or dysaesthetic vulvodynia. The latter is similar to causalgia, with a poor prognosis for resolution. Single patients had the following specific conditions: lichen planus, lichen sclerosus, mature neuroma and chronic candidiasis. The study shows that vulvodynia is a multifactorial problem for which management strategies have evolved over the course of time. Although interferon-alpha-2b offers much promise for the treatment of vulvodynia caused by subclinical HPV infection, the complete cure rate was only 58%. Overall 38% of patients still experience their problem, which indicates that they should be discouraged from going from physician to physician in the hopes of finding a 'cure'. PMID- 8191327 TI - The use of Doppler velocimetry of the umbilical artery before 24 weeks' gestation to screen for high-risk pregnancies. AB - OBJECTIVE: To describe the prevalence and natural history of absent end-diastolic velocities (AEDV) in the umbilical artery of the fetus between 16 and 24 weeks' gestation, and to evaluate its role as a screening test. DESIGN: Population-based descriptive study. SETTING: Tygerberg Hospital, Tygerberg, South Africa. The hospital serves a population from the lower socio-economic bracket. SUBJECTS: Doppler velocimetry was performed at routine ultrasound examinations for confirmation of gestational age in 496 women. MAIN OUTCOME MEASURES: The occurrence of perinatal death, small-for-gestational-age (SGA) babies and proteinuric hypertension. RESULTS: Forty-four (8.9%) patients had AEDVs at the first examination, but AEDV persisted in only 1. In this case, severe proteinuric hypertension developed unexpectedly at 29 weeks' gestation and the fetus needed delivery because of persistent late decelerations of the fetal heart rate pattern. There was a significant association between the group with AEDV at first examination and the development of proteinuric hypertension (P < 0.05), but no association with SGA babies. The association with proteinuric hypertension was too weak to be of clinical use. CONCLUSION: Doppler velocimetry of the umbilical artery, performed along with routine ultrasound examination to confirm gestational age, is not of use as a screening test for identifying high-risk pregnancies. PMID- 8191328 TI - Mid-trimester termination of pregnancy--a randomised controlled trial of two prostaglandin regimens. AB - OBJECTIVE: To determine the more applicable of two ways of prostaglandin induction currently in use in second trimester induced abortions for congenital or chromosomal abnormalities. DESIGN: A prospective randomised controlled trial. SETTING: Department of Obstetrics and Gynaecology, Tygerberg Hospital, CP. STUDY POPULATION: Twenty consecutive patients admitted for termination of pregnancy for congenital or chromosomal abnormalities between 14 and 26 weeks' pregnancy duration. MANAGEMENT: Patients were randomly selected to receive either 1.5 mg prostaglandin E2 (PGE2) gel extra-amniotically or 25 mg prostaglandin F2 alpha (PGF2 alpha) intra-amniotically. Patients in both groups received oxytocin to a maximum dosage of 120 mU per minute if they had not aborted 18 hours after the original administration of either prostaglandin regimen. If abortion had not taken place 36 hours after commencement of treatment, management was considered unsuccessful. MAIN OUTCOME MEASUREMENTS: Proportion of successful inductions and complications. RESULTS: Complications of management were rare and did not differ between the two management groups. However, there were significantly more failures in the group who received intra-amniotic PGF2 alpha (7 v. 2 patients) as well as a significantly higher need for oxytocin in this group (10 v. 4 patients). CONCLUSIONS: With promising drugs such as prostaglandin analogues and anti-progesterones not universally available, methods of induction suitable to the local situation should be sought. Extra-amniotic PGE2 seems more suitable than intra-amniotic PGF2 alpha because of a shorter induction-to-delivery time without increased morbidity. PMID- 8191329 TI - Do high fetal catecholamine levels affect heart rate variability and meconium passage during labour? AB - OBJECTIVES: To determine the relationship between umbilical arterial catecholamine levels and fetal heart rate variability and meconium passage. STUDY DESIGN: A prospective descriptive study was performed. Umbilical artery catecholamine levels were measured in 55 newborns and correlated with fetal heart rate before delivery, umbilical arterial pH, base excess and the presence of meconium-stained liquor. RESULTS AND CONCLUSION: The range of catecholamine levels was enormous, with very high epinephrine or norepinephrine levels in several fetuses. We were unable to demonstrate an association between high catecholamine levels and the presence of normal fetal heart rate variability despite acidaemia. We postulate that high catecholamine levels may inhibit fetal meconium passage. PMID- 8191330 TI - Persistent pulmonary hypertension of the neonate in a developing country--does extracorporeal membrane oxygenation have a role to play? AB - A retrospective study was undertaken of survival after conventional management of 35 infants suffering from persistent pulmonary hypertension of the neonate (PPHN). The outcome of infants weighing more than 2,000 g and who also qualified for extracorporeal membrane oxygenation (ECMO) therapy on the grounds of published criteria was assessed. The admission incidence of patients with PPHN was 1.1%. Secondary PPHN was more common than primary. The overall survival rate of 69% in this study reflects the trend in recently reported improved survival rates of infants with PPHN, treated with conventional techniques. Sixteen of 28 infants weighing more than 2,000 g qualified for ECMO therapy; 4 of them died. Had ECMO been available as an alternative mode of therapy, only 2 of the 4 might have been saved. The other 2 were considered to have conditions incompatible with a normal quality of life. We therefore assessed the requirement for ECMO in our population to be approximately 0.6/1,000 live births. Although ECMO may be promising, the introduction of this technique in developing countries should rather be delayed until more substantial data refute this. Because PPHN could be related to a potential preventable cause in almost 80% of cases, we propose the support of more cost-effective strategies such as continuing obstetric and perinatal education programmes. PMID- 8191331 TI - Selective posterior lumbosacral rhizotomy for the management of cerebral palsy spasticity. A 10-year experience. AB - One hundred and sixty-eight patients had selective lumbosacral posterior rhizotomies for the treatment of cerebral palsy spasticity at Red Cross War Memorial Children's Hospital and Groote Schuur Hospital during the 10-year period 1981-1991. There was no mortality and insignificant early postoperative morbidity. Long-term follow-up on 110 patients has revealed satisfactory tone reduction in 95% of cases. The majority showed improvement in standing, sitting and locomotion. Thirteen patients had minor persistent sensory disturbances and 20% have developed asymptomatic spondylolysis or grade I spondylolisthesis. Most therapists, patients and parents remain enthusiastic about the results of this procedure. PMID- 8191332 TI - Sero-epidemiology of hepatitis A in black South African children. AB - A community-based sero-epidemiological survey was undertaken to determine the age specific prevalence rates of hepatitis A virus (HAV) infection in a representative sample of 782 urban black children aged from newborn to 13 years. Among children aged 0-5 months, the prevalence of anti-HAV was 68.8% (95% confidence interval (CI) 60.6-77.0%); this fell to a low of 2.5% (CI 0.1-4.9%) in those aged 6-11 months, implying the presence of maternal antibody in the first few months of life. By the age of 2 years, 51.2% (CI 45.7-56.7%) had anti-HAV, by age 4 the prevalence had risen to 81.4% (CI 75.5-87.3%) and by age 6, the prevalence of anti-HAV was almost 100% (CI 90.5-96.7%), reflecting the poor socio economic and environmental conditions these children live in. The lowest prevalence of HAV infection among urban black South African children was during infancy, before the age at which the incidence rate rose sharply; e.g. 1 out of 5 children was already infected with HAV by its 2nd birthday. Vaccination in infancy will therefore have the biggest impact on the spread of HAV. However, before HAV vaccination in infancy is advocated, vaccine immunogenicity in infancy and the possible detrimental effect of maternal antibodies on the immunogenicity of the vaccine need clarification. PMID- 8191333 TI - Congenital pseudarthrosis of the tibia--treatment with free vascularised fibular grafts. AB - Congenital pseudarthrosis is uncommon. We report on a series of 4 patients treated by means of free vascularised fibular grafts. Complications encountered were graft fracture, delayed union and angulation deformities. Modifications in the surgical technique improved later results. We recommend wide excision of pathological bone, bridging of the defect by free vascularised fibular grafts and rigid fixation. PMID- 8191334 TI - A role for the ecological study in the developing world. AB - Retrospective case-control or prospective (follow-up) studies are important epidemiological tools and have provided useful information on exposure disease associations. Prospective studies would be the ideal option, but many countries (particularly in the developing world) do not have the necessary infrastructure to follow people up. Both retrospective and prospective studies are, however, sometimes conducted without due regard for their own limitations. These limitations are exacerbated when measures of exposure or disease are based on a single measurement and where the population under study is homogeneous with regard to exposure. The former is responsible for regression dilution bias and the latter for a lack of contrasts between exposure groups. Both factors would attenuate any relationship between exposure and disease. Ecological studies in epidemiology are weaker in design than case-control or prospective studies, but in some circumstances an ecological approach, which looks at the prevalence of an exposure or disorder in a number of areas of varying disease rates, may offer some advantages. PMID- 8191335 TI - Clinical research. PMID- 8191336 TI - Guidelines for the practice of gastro-intestinal endoscopy. A statement by the South African Gastroenterology Society (SAGES) Council. PMID- 8191337 TI - Measles warning from Port Elizabeth. PMID- 8191338 TI - Equity versus humanity in health care. PMID- 8191339 TI - Inappropriate antenatal care. PMID- 8191340 TI - Cushing's syndrome--a reversible cause of malignant hypertension. PMID- 8191341 TI - Relapse in malaria. PMID- 8191342 TI - Indications for colonoscopy. PMID- 8191343 TI - Advances in islet cell transplantation for insulin-dependent diabetes. PMID- 8191345 TI - Fentanyl for epidural analgesia. PMID- 8191344 TI - Provision of epidural analgesia by obstetricians. PMID- 8191346 TI - Disposable chemical oxygen generators. PMID- 8191347 TI - Intravascular intra-uterine transfusions for severe fetal iso-immunisation. PMID- 8191348 TI - The most common cancers in Transkeian adults by histological diagnosis. PMID- 8191349 TI - Oesophageal cancer in three regions of South Africa. PMID- 8191350 TI - Lowering the risk of coronary heart disease. PMID- 8191351 TI - Who is responsible for urinary catheterisation? PMID- 8191352 TI - Complications of laparoscopic surgery. PMID- 8191353 TI - Laparoscopic intracorporeal ultrasound. An alternative to cholangiography? AB - The purpose of this study was to compare laparoscopic intracorporeal ultrasound (LICU) examination of the biliary duct system with cholangiography for delineation of duct anatomy and determination of presence or absence of ductal calculi. Thirty-one patients had LICU examination of the extrahepatic bile ducts after exposure of the gallbladder but prior to dissection of the cystic duct. After LICU examination, cystic duct dissection and cholangiography were done. Evaluation of duct anatomy and decision for duct exploration were based on findings of both tests. All patients had successful LICU examination and 30 had successful cholangiography. Duct size as determined by LICU corresponded precisely with cholangiography. LICU provided useful anatomical information in two patients with aberrant anatomy and detected cholangiogram. LICU aids in delineation of biliary duct anatomy and accurately determines presence or absence of duct calculi. PMID- 8191354 TI - The anatomy of the hepatoduodenal ligament in laparoscopic sonography. AB - Laparoscopic sonography was introduced at our institution in April 1991. It is presently being tested as an alternative to peroperative cholangiography as far as the visualization of the structures of the hepatoduodenal ligament- particularly the extrahepatic bile ducts--during laparoscopic cholecystectomy are concerned. So far, 75 patients have been examined with both modalities. The structures of the hepatoduodenal ligament could be seen sonographically in all patients, while in five patients, the cholangiography had to be aborted for technical reasons. Eleven patients (15%) had anatomical variations of the bile ducts. Nine of these were diagnosed sonographically. A duodenal diverticulum and a long common channel of common bile duct and pancreatic duct were seen only on cholangiography. Variations of the hepatic arteries were found in 15 patients (20%). We conclude that intraoperative laparoscopic sonography is a reliable tool for the visualization of the structures of the hepatoduodenal ligament. This new technique might replace peroperative cholangiography in the future. PMID- 8191355 TI - Abdominal adhesions in laparoscopic hernia repair. An experimental study. AB - Laparoscopic herniorrhaphy is becoming an increasingly common procedure. The possible creation of intraperitoneal adhesions during laparoscopic herniorrhaphy has not been examined. For the transperitoneal hernia repair to be an acceptable option, the hypothesis that this approach will incite significant adhesions must be rejected. To test this hypothesis, 21 pigs underwent laparoscopic herniorrhaphy using a standard procedure with the implantation of a polypropylene mesh graft on one side while a sham procedure was performed on the other. These animals were later examined laparoscopically for adhesion formation and the condition of the graft. None of the 21 animals developed adhesions to the trocar sites, 12 animals developed adhesions to the area of the polypropylene mesh, and 3 developed adhesions to the side of the sham procedure. There were no adhesions involving the small intestine. It is therefore concluded that the hypothesis should be rejected and that laparoscopic herniorrhaphy does not incite significant adhesions. PMID- 8191356 TI - Unrecognized hazards of surgical electrodes passed through metal suction irrigation devices. AB - Surgical electrodes, passed through metal suction-irrigation devices, pose significant risks for unrecognized visceral burns through capacitively coupled current using monopolar electrosurgery. Plastic cannulas (and reducers) should be avoided with the metal suction-irrigation electrode; an all-metal trocar cannula confers limited safety. With surgeon education and advances in engineering, the potential for unrecognized visceral injury with capacitive coupling can be eliminated. PMID- 8191357 TI - Treatment of bile leaks from the cystohepatic ducts after laparoscopic cholecystectomy. AB - The cystohepatic ducts represent accessory bile ducts of variable size which frequently travel within the gallbladder fossa or in the posterior wall of the gallbladder. These ducts can be injured during laparoscopic cholecystectomy and can result in bile collections if transected. Successful treatment by operative means or radiologically guided percutaneous drainage is possible, but endoscopic management has several advantages. We describe cases managed by endoscopic retrograde cholangiopancreatography (ERCP) with stent placement and discuss the advantages of this method. Also discussed is the anatomy of these accessory bile ducts, additional management options, and techniques for avoiding this injury during open or closed cholecystectomy. PMID- 8191358 TI - Thermal injury of the posterior duodenum during laparoscopic cholecystectomy. AB - While complications of laparoscopic cholecystectomy occur in 3-7% of cases, bowel injuries are uncommonly reported. Bowel injuries appear to be of two types: penetrating bowel injury from either the Veress needle or trocar, and thermal bowel injury from either contact or conductive burn. The duodenum is usually spared from Veress needle or trocar injury because of its posterior location. However, during dissection in the triangle of Calot, the duodenum is at risk for direct contact burn or energy conduction burn. In this report we describe a presumed conductive burn injury of the posterior second portion of the duodenum which followed laparoscopic cholecystectomy. This unrecognized injury resulted in full-thickness necrosis of the duodenal wall with delayed perforation. This injury was successfully managed with pyloric exclusion. The diagnosis and management of this previously unreported injury are described. PMID- 8191359 TI - Hepatic artery pseudoaneurysm and hemobilia following laser laparoscopic cholecystectomy. A case report. AB - This report describes injury to the hepatic artery with pseudoaneurysm formation and hemobilia following the use of laser-assisted dissection to perform laparoscopic cholecystectomy. A 57-year-old woman was referred emergently 2 weeks after laser laparoscopic cholecystectomy with upper abdominal pain, upper gastrointestinal bleeding, and jaundice. A selective hepatic arteriogram showed a right hepatic artery pseudoaneurysm which was embolized. Two weeks later the patient had recurrent hemobilia as the result of blood flow restoration in the pseudoaneurysm and a fistula to the cystic duct remnant. She was treated with two additional embolizations and direct injection of the aneurysm with thrombogenic material. Follow-up at 2 years showed no further recurrence. Since the laser has never been shown to have advantages over electrocautery, its use during laparoscopic cholecystectomy is difficult to justify. PMID- 8191360 TI - Bile leak from the liver bed following laparoscopic cholecystectomy. AB - Intraperitoneal accumulation of bile from accessory bile ducts following cholecystectomy is an uncommon, but well-described, occurrence. It is not unique to laparoscopic cholecystectomy. The presence of accessory channels between the liver and gallbladder has long been recognized by anatomists and surgeons. They are commonly known as the "ducts of Luschka". Recognition and treatment of liver bed bile leaks vary. Usually the surgeon can treat this problem without an exploratory celiotomy depending on availability of ERCP or interventional radiology. This article will review clinical diagnosis, radiologic confirmation, and treatment for this complication. PMID- 8191361 TI - Intrahepatic subcapsular biloma. A rare complication of laparoscopic cholecystectomy. AB - Bile leaks leading to bilomas in the subhepatic space are amongst the most common complications of laparoscopic cholecystectomy (LC). We describe the case of a large (1,100 cc) intrahepatic biloma that presented with pain and fever 14 days post LC. The diagnosis was suspected as a result of ultrasound and CT scan and the problem was solved by percutaneous catheter drainage. We believe this intrahepatic biloma was caused by a lesion of an abnormal bile duct near the bed of the gallbladder during a difficult dissection due to severe contraction and fibrosis. PMID- 8191362 TI - Unsuspected carcinoma of the gallbladder. A laparoscopic dilemma. AB - Laparoscopic cholecystectomy is the treatment of choice for gallstones. A formal contraindication is gallbladder cancer. However, in a great number of cases, this is a previously unsuspected intraoperative finding, and sometimes its first appearance is in acute cholecystitis. We present the case of 67-year-old woman, which presented an unsuspected carcinoma of the gallbladder that developed abdominal wall implants at the umbilical and left hypocondrium site. The success of LC favors the observation of cases similar to that described in this article. Surgeons who operate using laparoscopic techniques should bear this possibility in mind and practice an extemporaneous biopsy at the slightest suspicion of malignancy, and, if it is confirmed, the operation should be continued as an open one. PMID- 8191364 TI - An overview of UTDB's history. PMID- 8191363 TI - Pulmonary embolism following laparoscopic cholecystectomy: report of two cases and review of the literature. AB - Laparoscopic abdominal surgery is considered a low-risk procedure for postoperative thromboembolic disease. We report two cases of pulmonary embolism following laparoscopic cholecystectomy, review the incidence of deep venous thrombosis and pulmonary embolism in laparoscopic cholecystectomy, and suggest a specific prophylactic scheme for patients undergoing laparoscopic cholecystectomy. In spite of the low incidence of postoperative thromboembolic disease following minimally invasive procedures, the risk of pulmonary embolism must not be underestimated and its symptoms must not be underdiagnosed. PMID- 8191365 TI - The future of the dental branch. PMID- 8191366 TI - Infection-control considerations in the dental laboratory. PMID- 8191367 TI - Is mom "losing it"? PMID- 8191368 TI - Battleship Texas--a floating city, dental office and all. PMID- 8191369 TI - Anesthesiology as a specialty in dentistry. PMID- 8191370 TI - Save your practice $50,000! The Americans with Disabilities Act (ADA) as a tool, not a cavity. PMID- 8191371 TI - Twentieth century history and contemporary issues facing dental anesthesiology. PMID- 8191372 TI - Is there a need for a specialty in dental anesthesia? PMID- 8191373 TI - The failed dental appointment case report: the phobic gagger. PMID- 8191374 TI - Dentist-anesthesiologists' practice profiles and case presentations. PMID- 8191375 TI - Dissociative sedation. PMID- 8191376 TI - [Neurology as an independent specialty]. PMID- 8191377 TI - [The history of epileptology]. PMID- 8191378 TI - [Headache--what is the current status?]. AB - Clinical and experimental evidence suggest, that migraine reflects a biological disorder of the brain. On the basis of a genetic predisposition, variations in internal rhythms may change the responsiveness towards external trigger factors. During the migraine attack changes occur in the cortical neuronal activity, in cerebral blood flow and in the activity of neuropeptide neurotransmitters such as substance P and calcitonin-gene-related-peptide. The consequence is an aseptic inflammation in the wall of dural arteries. Sumatriptan is a new agent which selectively acts at 5-HT-1D receptors in brain vessels and improves headache and autonomic symptoms in severe migraine attacks. Sumatriptan is also helpful in the treatment of headache attacks in cluster headache. The treatment of chronic tension-type headache requires the combination of tricyclics with behavioral techniques such as relaxation training. PMID- 8191379 TI - [Lumbalgia--how to proceed?]. AB - In more than 80% of these patients no objective pathologic cause can be found and in most the disorder is self limited and benign. Nonetheless, a systematic approach to LBP should identify those patients with a serious disorder requiring special treatment. Thorough examination is the basis of treatment and management of these patients at risk for back pain disability with enormous socio-economic consequences. Psychosocial factors are at least as predictive for disability as physical. PMID- 8191380 TI - [Epilepsy--diagnosis and therapy]. AB - Epilepsy is a common condition with an overall point prevalence of 1%. For the diagnosis the recording of family/personal history and a seizure description from an observer are most important. The indications and the treatment with antiepileptic drugs, the management of status epilepticus and the possibility of surgical operation are discussed. The great importance of a regular lifestyle and good compliance is pointed out. PMID- 8191381 TI - [Polyneuropathies--symptoms, causes and diagnostic procedure]. AB - The diagnosis of a polyneuropathy (PNP) is particularly a clinically based diagnosis. The polyneuropathic syndrome consists of typical symptoms like paraesthesias, pain, cramps and fasciculations as well as characteristic signs like loss of tendon reflexes, weakness and wasting of muscles, sensory loss, cranial nerve palsy and alterations of the autonomic nervous system. The analysis of manifestation-types is very important for the differential diagnosis. The symmetrical sensory type of manifestation can be found in the beginning of almost all toxic neuropathies as well as in uremic and diabetic neuropathy. The symmetrical-motor type of manifestation can be a further development of the symmetrical sensory type of manifestation or exists from the beginning in the case for example of Guillain-Barre-Syndrome. The asymmetric type of manifestation can be observed in the vascular neuropathies and in some types of inflammatory neuropathies like the neuroborrelioses or the neuralgic amyotrophy. The investigation of the CSF, electromyography and electroneurography as well as a great number of chemical lab tests are important for the etiological classification. According to the etiology, the polyneuropathies can be subdivided into four groups such as inflammatory, vascular, exotoxic and endotoxic-metabolic hereditary diseases. The most frequent etiologies are diabetes mellitus and chronic alcoholism. PMID- 8191382 TI - [Idiopathic Parkinson syndrome--current therapy]. AB - At present we dispose of a number of medical, surgical and other measures for the treatment of patients suffering from idiopathic Parkinson's disease. Some guidelines for the adaptation of the treatment for the individual patient will be given. Special attention will be given to the question of a possible neuroprotective treatment. PMID- 8191383 TI - [Management of cerebrovascular stroke]. AB - Strokes are classified according to their time course, involved vascular territory and etiology. For this purpose the important clinical symptoms and signs are reviewed and a rational use of the diagnostic tools is suggested. Mostly depending on the etiology of a stroke, decisions for treatment and prophylaxis are made. Treatment consists in general medical management and in most cases use of anticoagulants and aspirin, which have proved efficacious in prevention of recurrent stroke. Two studies have also proved the prophylactic value of carotid endarterectomy after stroke. PMID- 8191384 TI - [Therapeutic approach to epilepsy]. PMID- 8191385 TI - [Historic mile stones in the diagnosis and therapy of lung tumors]. PMID- 8191386 TI - [Morphological diagnosis and classification of lung tumors]. AB - Morphologic examination is mandatory for distinction between benign and malignant pulmonary lesions and separation of primary tumors from metastatic disease. Tumors are classified as to their type and grade by histology and/or cytology. Differences in behavior and response to treatment make the distinction between small cell carcinoma [SCLC] and non-small cell carcinoma [NSCLS] the single most important decision the pathologist must make when examining a lung tumor. The considerable cellular heterogeneity of bronchogenic carcinoma may be the source of problems and pitfalls in morphologic classification of these tumors, discussed in this review together with the concept of neuroendocrine neoplasms. PMID- 8191387 TI - [Lung tumors: symptoms, clinical signs, evaluation and staging]. AB - The signs and symptoms of the predominantly malignant lung tumors primarily depend on the site and the local infiltration of the tumor as well as on the extent of metastatic dissemination and the paraneoplastic syndromes. The investigation--mainly on an outpatient basis--includes three phases. The first step is the cytological and/or histological identification of the tumor, usually by means of chest X-ray, sputum examination, bronchoscopy or more invasive methods. Beginning with computed tomography, the goal of the second step is the staging of the extent of the disease. Patients with small-cell lung cancer [SCLC], which is considered to be primarily nonresectable, are classified as having either limited or extensive disease. A survival difference has been reported between the two stages. In order to define the potentially resectable forms [25%] of non-small-cell lung cancer [NSCLC], the TNM classification is applied. Finally, it has to be estimated whether the patient is fit for major surgery. PMID- 8191388 TI - [Radiological diagnosis of lung tumors]. AB - Tumor detection, differential diagnosis, clinical staging and follow-up information are the main aims in imaging lung tumors. The contribution of specific imaging methods, above all chest radiography and CT, is discussed for lung cancer, the clinically most important entity. Despite the lack of histologic information, noninvasive methods currently play an important role in the clinical management of lung tumors. PMID- 8191389 TI - [Surgery of lung tumors]. AB - Indeterminate solitary pulmonary nodules deserve prompt histologic confirmation, which is easily and efficiently achieved by thoracoscopic wedge resection. Patients with stage I to IIIa NSCLC are best treated by complete tumor resection (lobectomy/pneumonectomy) and mediastinal lymph node dissection. However, induction (radio)chemotherapy followed by surgical resection is increasingly performed for locally advanced NSCLC, since this offers far better results than surgery or radiotherapy per se, especially for bulky N2 disease. Surgical resection of pulmonary metastases is certainly indicated in selected patients, and the outcome is strongly related to the completeness of tumor removal. Patients with peripheral solitary lung metastases are increasingly treated by thoracoscopic wedge resection, followed by CT-scans at regular intervals. PMID- 8191390 TI - [Pulmonary nodules]. AB - Solitary pulmonary nodules 3 cm or greater in diameter should be regarded as probably malignant. Single spherical lesions of smaller size are in about 30% primarily bronchogenic carcinomas, in 10% solitary metastatic deposits and in about 60% benign nodules, commonly infectious granulomas. The generally accepted criteria for benignity are the detection of a "benign" pattern of calcification, no growth over the preceding two years, minimal exposure to tobacco, and the age under 30 years. In general, resectable malignant solitary nodules should be identified and removed. Metastatic tumor deposits are the most common cause of multiple nodules. PMID- 8191391 TI - [Case of the month: pulmonary nodule in a non-smoking female patient with chronic rheumatoid arthritis]. PMID- 8191392 TI - Expression of fibrinogen receptors on platelets of uremic patients is correlated with the content of GPIIb and plasma level of creatinine. AB - Platelets of uremic patients, activated with ADP, exposed less fibrinogen receptors than control platelets, i.e. 24612 +/- 5541 and 33400 +/- 4302 receptors per platelet, respectively. However, this difference was not statistically significant. When compared with the total number of GPIIb/IIIa complexes, quantified from platelet glycoprotein IIb (GPIIb) contents, active receptors on the platelet surface represented 13.6% and 35.1% of total pool of fibrinogen receptors in uremic and control platelets, respectively. The number of exposed fibrinogen receptors was positively correlated with the amount of GPIIb copies in both uremic and normal platelets. In uremic platelets, both the number of exposed receptors and the number of GPIIb copies were correlated with the plasma creatinine concentration suggesting, that binding of fibrinogen to uremic platelets depends upon the degree of renal failure. Uremic platelets contain similar amounts of fibrinogen as control ones i.e. 13.2 +/- 2.3 micrograms and 17.6 +/- 2.2 micrograms per 1 x 10(8) platelets, respectively. Whereas for beta thromboglobulin (beta-TG) there was a significant difference of 392 +/- 102 ng and 803 +/- 202 ng per 1 x 10(8) platelets, respectively. Reduced beta-TG content in uremic platelets suggests limited platelet activation in vivo. These results support the concept that uremic platelets have impaired functions and indicate that there is a relationship between the progression in renal failure and disability of platelets in thrombosis. PMID- 8191393 TI - Enhanced thrombin generation in children with sickle cell disease. AB - Recent studies suggest that increased activity of the coagulation system, measured with sensitive assays for activation markers, may be important in the pathogenesis of vascular occlusion in sickle cell disease (SCD). Since most of these studies were carried out in adult patients and SCD is an inherited disorder with severe morbidity even in childhood, we decided to determine the activity of the coagulation system in children with SCD. In a prospective study markers of thrombin generation as well as coagulation inhibitors were investigated in 16 homozygous SCD patients and 16 age-matched control children. Significantly increased plasma concentrations of the prothrombin fragment F1+2 and of thrombin antithrombin III (TAT) complexes were found in SCD patients. The levels of protein C activity and total and free protein S were significantly reduced in SCD patients as compared with control values. Plasma AT III levels were not different in the two groups. We conclude that, in children with SCD, evidence of enhanced thrombin generation is present, which may in part be due to reduced levels of the inhibitors proteins C and S. The clinical relevance of this coagulation imbalance has to be demonstrated. PMID- 8191394 TI - The use of intermediate and high purity factor VIII products in the treatment of von Willebrand disease. AB - Since 1985, viral-attenuated blood products have been available for the treatment of patients with hemophilia. Unfortunately, similar viral-attenuated blood products, enriched for von Willebrand factor (vWF), have not been readily available for the treatment of patients with von Willebrand disease (vWD). In the current study, we examined the clinical efficacy and in vivo properties of two viral-attenuated factor VIII products, Koate-HS and Koate-HP, in the treatment of patients with vWD. Twenty-one (21) infusions were evaluated in 17 different vWD patients (4 with type IA; 8 with Type IIA; 1 with Type IID; 4 with type III). Seven (7) patients received Koate-HS and 12 patients received Koate-HP (2 patients received both products; 1 patient was studied three times). Von Willebrand factor antigen, ristocetin cofactor, bleeding time, and the multimeric composition of vWF were determined pre- and post-infusion. Complete or partial correction of prolonged bleeding times was observed in 2 of the 6 patients tested following treatment with Koate-HS and in 7 out of 11 patients tested following treatment with Koate-HP. Surgery was performed on five of these patients, two of whom were treated with Koate-HS and three of whom were treated with Koate-HP. In the surgical patients, clinical hemostasis was achieved regardless of whether the bleeding time was corrected. We conclude that both Koate-HS and Koate-HP can be utilized successfully in the treatment of patients with vWD in spite of the lack of high molecular weight multimers of vWF in these products.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191395 TI - Relation of habitual diet and cardiorespiratory fitness to blood coagulation and fibrinolytic factors. AB - The relation of habitual diet and cardiorespiratory fitness to plasma fibrinogen concentration, Factor VII activity (F VIIc), Factor X activity (F X), tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1) concentrations, anti-thrombin III (AT III) and apolipoprotein(a) (Apo[a]) was analyzed in 111 normolipidemic men aged 51-53 years. Diet was evaluated by seven day food records. Maximal oxygen consumption and aerobic threshold were determined in maximal bicycle ergospirometry test based on breath-by-breath analysis of expired respiratory gas. Plasma fibrinogen was measured by thrombin method, F VIIc by one-stage coagulation method, AT III and F X colorimetrically, t-PA and PAI-1 antigens by ELISA and Apo(a) concentration radioimmunologically. Carbohydrate intake was negatively (r = -0.31, p < 0.001; r = -0.24, p < 0.01; r = -0.36, p < 0.001) and fat intake positively (r = 0.24, p < 0.01; r = 0.29, p < 0.001; r = 0.32, p < 0.001) related to F X, PAI-1, and t-PA, respectively. Aerobic threshold correlated negatively with fibrinogen (r = -0.33, p < 0.001) and F X (r = -0.30, p < 0.001). Fasting insulin was the strongest determinant for PAI-1 (r = 0.55, p < 0.001) and a significant positive correlate to F VIIc (r = 0.30, p < 0.001), F X (r = 0.28, p < 0.01) and t-PA (r = 0.47, p < 0.001). These data emphasize the importance that carbohydrate rich diet and cardiorespiratory fitness may have against thrombogenesis. PMID- 8191396 TI - High-titer antinuclear antibodies, anti-SSA/Ro antibodies and anti-nuclear RNP antibodies in patients with idiopathic thrombocytopenic purpura. AB - The clinical significance of high-titer antinuclear antibodies (ANA) and autoantibodies to cellular antigens such as SSA/Ro and nuclear RNP (nRNP) antigens in idiopathic thrombocytopenic purpura (ITP) was examined in a prospective evaluation of 66 adult patients with chronic ITP. ANA were positive in 29 (44%) of 66 patients with chronic ITP. The titers of ANA were high (1:160 or higher) in 14 of 29 ANA-positive patients. Furthermore, 10 of 66 patients had precipitating antibodies to nuclear antigens; seven patients had anti-SSA/Ro antibodies and the other three had anti-nRNP antibodies. None of high-titer ANA- or precipitating antibody-positive patients developed systemic lupus erythematosus (SLE) throughout the follow-up period of 3 years. In addition, we investigated retrospectively precipitating antibodies in stocked sera from 8 patients. These patients had already precipitating antibodies average of 7.7 years before. None of 8 patients developed SLE or Sjogren's syndrome (SS). These data demonstrate that high-titer ANA and antibodies to SSA/Ro or nRNP antigens are often found in patients with ITP, and indicate that the detection of high titer ANA or the existence of antibodies to SSA/Ro or nRNP antigens by itself is not enough to identify those patients with ITP who are at risk of developing SLE or SS. PMID- 8191397 TI - A comparative study on the quality of oral anticoagulant therapy (warfarin versus acenocoumarol). AB - In our Center for the Surveillance of Anticoagulant Treatment, most of the 1700 patients followed-up are traditionally treated with acenocoumarol, while warfarin is administered nowadays to an increasing proportion of patients. To assess if the difference in the pharmacokinetics of these two drugs may determine a different laboratory quality of treatment, a retrospective study was performed on the computerized files of all 142 patients on treatment with warfarin for more than 100 days and on a control group of 142 patients treated with acenocoumarol, matched for age, sex, disease state and duration of oral anticoagulant therapy (OAT). The study considered 7071 assays for a total of 432 patient-years of treatment. The overall quality of treatment was significantly better in patients treated with warfarin (72% of controls within the therapeutic range versus 67% on acenocoumarol, p < 0.001). Also the individual quality of therapy, which was assessed as the percentage of patients with 75% or more assays in range, was in favour of warfarin (50.7% vs 34.5%, p < 0.05). Warfarin therapy was more stable and fewer assays were required for treatment monitoring. Confounding factors possibly influencing the treatment stability, such as interfering drugs, diagnostic or therapeutical procedures requiring withdrawal of anticoagulation, were evaluated and no significant difference between the two groups was found. The difference in the laboratory quality of OAT was marked in patients treated for prevention of arterial thromboembolism, while it was negligible in patients with venous thromboembolic disease, whose mean duration of OAT was considerably shorter. Since there is no evidence that acenocoumarol is more efficacious or safer than warfarin, the latter seems to be preferable for patients who are candidate to very prolonged OAT. PMID- 8191398 TI - Familial idiopathic osteonecrosis mediated by familial hypofibrinolysis with high levels of plasminogen activator inhibitor. AB - Familial hypofibrinolysis with 3 generation, autosomal dominant, very high levels of plasminogen activator inhibitor activity (PAI-Fx) and antigen (PAI-Ag) was etiologically associated with bilateral idiopathic osteonecrosis in 2 brothers. They, their mother, 2 brothers, sister, and all 4 of her children (none of whom had yet developed osteonecrosis), all had very high PAI and could not elevate tissue plasminogen activator after 10 minutes of venous occlusion at 100 mmHg. Familial high PAI levels with concurrent hypofibrinolysis co-segregated with familial combined hyperlipidemia, both being independent risk factors for premature coronary heart disease. If thrombi block venous drainage in the femur, familial hypofibrinolysis mediated by familial high PAI with inability to lyse thrombi would contribute to venous hypertension of bone, bone anoxia, and bone death characteristic of osteonecrosis. PMID- 8191399 TI - Low affinity heparin is an antithrombotic agent. AB - We have investigated the antithrombotic activities and haemorrhagic side effects of a low affinity heparin (LAH). In the rabbit thrombosis model using activated human serum as the thrombogenic challenge, the effect of LAH on 10' and 20' stasis was studied. At 10' stasis, 150 micrograms/kg of LAH reduced thrombus formation by 67% and total prevention was achieved at 500 micrograms/kg. At 20' stasis, 150 micrograms/kg was totally ineffective, 500 micrograms/kg was partially effective and 1000 micrograms/kg was required to achieve complete prevention of thrombosis. Mean peak circulatory level following infusion of 500 micrograms/kg of LAH was found to be 1.6 micrograms/ml by heparin cofactor II based assay and 0.13 iu/ml by anti-factor Xa assay. Thrombin generation tests of the same post injection samples showed an 80% reduction in thrombin production when compared with pre-injection samples. At 2.5 mg/kg, the mean bleeding time ratio (challenge:control) measured in the rabbit ear template model was 1.25 (cf saline control 0.88). Compared with results from previous studies on unfractionated heparin and dermatan sulphate, LAH is approximately 6 times less effective than UFH but 5 times more potent than dermatan sulphate. Since the mean bleeding time for UFH at 2.5 mg/kg was previously found to increase nearly two fold over the control value, LAH may present a lesser haemorrhagic risk than UFH. These data suggest that LAH is more effective in directly preventing venous thrombosis than dermatan sulphate. Although LAH is not as effective as UFH on a weight basis in the impairment of thrombogenesis, it may carry significantly lower bleeding risk. PMID- 8191400 TI - Measurement of tissue factor messenger RNA levels in human endothelial cells by a quantitative RT-PCR assay. AB - We have developed a sensitive and quantitative RT-PCR assay for the determination of tissue factor (TF) mRNA levels in human cells. An in vitro synthesized internal standard RNA was used to correct for differences in reverse transcription or amplification of various RNA samples. The PCR products were quantitated by hybridization. The sensitivity was such that less than 0.2 microgram of total endothelial RNA sufficed to measure its TF mRNA content. The RT-PCR assay was used to determine TF mRNA levels in endothelial cells treated with a factor from human melanoma cells and/or TNF. In this way the amount of TF mRNA could be induced to a level that was at least 80-fold higher than that in non-induced cells. This increase was in the same order of magnitude as the induction of measured TF activity. PMID- 8191401 TI - Antithrombotic effect of recombinant truncated tissue factor pathway inhibitor (TFPI1-161) in experimental venous thrombosis--a comparison with low molecular weight heparin. AB - The aim was to investigate whether a truncated recombinant Tissue Factor Pathway Inhibitor (TFPI1-161), which lacked the third Kunitz-type domain and the basic c terminal region, had an antithrombotic effect comparable to LMWH in a randomised double-dummy study. The experimental thrombosis was induced in jugular veins, in a total of 40 rabbits by a combination of destruction of the endothelium and restricted blood flow. Group 1: placebo, gr 2: LMWH 60 anti-FXa IU/kg, gr 3-5: 0.1, 1.0 and 10.0 mg/kg TFPI1-161. TFPI1-161 reduced the thrombus weights in all treated groups, significantly in doses of 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis and occlusive thrombosis were also significantly reduced in those doses. The antithrombotic properties of TFPI1-161 (1.0-10.0 mg/kg) measured as thrombus weight, frequency of thrombosis and frequency of occlusive thrombosis was equivalent to the anti-thrombotic properties of LMWH. In the anti-FXa, APTT and PT-assays TFPI1-161 displayed a dose dependent increase of activity. Recombinant-TFPI1-161 did not influence the anti-FIIa-assay. No haemorrhagic side effects were noted. PMID- 8191402 TI - Two different incubation times for the activated partial thromboplastin time (APTT): a new criterion for diagnosis of lupus anticoagulant. AB - We describe a test for LA based on the specific APTT behaviour of LA plasmas when the incubation time with the APTT reagent is increased from 1 to 20 min. "1-10 APTT" test was defined as the difference (s) between results of the APTT performed with 1 and the one performed with 10 min incubation. A test value > 11 s (upper normal limit determined on 134 normal plasmas) was considered positive for a LA. The test distinguished all the LA patients studied (n = 40) from patients with factor VIIIc inhibitors, patients receiving heparin or warfarin therapy and also patients with congenital factor deficiencies, except those with prekallikrein and factor XII deficiencies. The test detected LA in warfarin (n = 3) and in heparin (n = 2) LA anticoagulated patients. Among 195 patients referred for LA screening, the test detected LA in 5 patients with normal standard APTT. This simple test, using a single reagent for screening and confirmatory procedures is sensitive and fairly specific for LA when combined with mixing studies. However, since the test was defined using one APTT reagent, the performances of other reagents have to be assessed. PMID- 8191403 TI - A sensitive ELISA for human tissue-type plasminogen activator applicable to the study of acute release from cultured human endothelial cells. AB - The development of a highly sensitive, enzyme-linked immunosorbent assay (ELISA) for tissue-type plasminogen activator (tPA) is described. The use of a biotin avidin system resulted in a detection limit of 10 pg of tPA per ml, which is 50 to 150 times more sensitive than commercially-available ELISAs. Free tPA and tPA complexed to PA inhibitor type-1 were detected with equal efficiency. The ELISA proved suitable for measuring tPA antigen in conditioned media and in cell extracts. The intra-assay coefficient of variation varied in six different experiments from 1.9% to 3.4% in the range 0 to 250 pg of tPA antigen per ml. The inter-assay coefficient of variation was 7% (n = 6). The ELISA was used to study the acute release of tPA from human umbilical vein endothelial cells in vitro. Upon addition of thrombin (1 NIH U/ml) to endothelial cells, tPA was rapidly released into the medium, the highest release occurring during the first minute. Concomitantly, the tPA concentration in the cell extracts decreased. Evidence is presented that tPA is released from an intracellular source. PMID- 8191404 TI - Flow through clots determines the rate and pattern of fibrinolysis. AB - Thrombolytic therapy depends on penetration of plasminogen activator into clots which occurs through diffusion and flow. An in vitro system has been developed to characterize the rate and pattern of fibrinolysis in relation to flow through occlusive clots exposed to a pressure gradient. Whole blood clots formed in plastic tubes were perfused with plasma containing 1 microgram/ml tissue plasminogen activator (t-PA) and 0.5 or 1 mmol/l gadolinium-diethylentriamine pentaacetic acid (Gd-DTPA), a paramagnetic substance used as a contrast enhancer for magnetic resonance (MR) imaging. T1-weighted spin echo MR images were obtained during clot perfusion at 3-5 min intervals for 45 min. Characteristic signal intensities allowed identification of non-perfused, perfused but non lysed, and completely lysed areas of clot. A spatially resolved time course of perfusion and subsequent lysis was constructed for 10 clots. Plasma flowed non uniformly through clots forming asymmetric channels that left some areas non perfused. The longitudinal velocity of flow through the dominant channel was 1.6 +/- 0.7 mm/min. The flow rate during the first five minutes was 7.5 +/- 6.5 microliters/min and 15.3 +/- 10 microliters/min between min 26-30 in clots that had not completely recanalized by that time. A sharp increase in flow was noted at the time of recanalization that occurred at 37 +/- 11 min. Clot lysis followed the pattern of perfusion through the dominant channel after a lag time of 13 +/- 4 min, representing the time required for enzymatic processes. The delay time between perfusion and lysis was longer in regions with slower flow indicating that the rate of t-PA delivery influenced the rate of fibrinolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191405 TI - Differences in u-PA and t-PA increase during acute exercise: relation with exercise parameters. AB - Plasma levels of urokinase-type (u-PA Ag) and tissue-type (t-PA Ag) plasminogen activator are both enhanced during physical exercise. Whether, the extent of the increase and the post-exercise clearance rate of the two activators are comparable is not known. We studied the changes in u-PA Ag, t-PA Ag and t-PA activity during a standardized exercise test comprising submaximal and maximal exercise intensity. During submaximal (recreational) exercise, increases in u-PA are mainly due to changes in plasma volume, submaximal exercise demonstrates a continuous rise in level of t-PA Ag. During maximal performance peak levels of u PA and t-PA Ag do not coincide in time and magnitude, moreover, u-PA Ag rather than t-PA Ag is related to t-PA Act. From these results we conclude that independent mechanisms regulate the exercise-induced plasma levels of u-PA and t PA. PMID- 8191406 TI - Platelets from bleeding Simmental cattle mobilize calcium, phosphorylate myosin light chain and bind normal numbers of fibrinogen molecules but have abnormal cytoskeletal assembly and aggregation in response to ADP. AB - We have evaluated platelet function in normal Simmental cattle and in those with a congenital, inherited bleeding disorder previously attributed to impaired platelet aggregation. Affected platelets failed to aggregate and secrete in response to ADP and the ionophore A23187, and showed impaired aggregation responses to collagen and ionomycin. Aggregation and secretion of normal and affected platelets was similar in response to thrombin and PMA. Resting cytosolic calcium levels and calcium mobilization in response to ADP and ionomycin were similar in control and four affected animals. Normal and affected bovine platelets phosphorylated myosin light chain and pleckstrin in response to ADP and A23187. Transmission electron microscopy of affected platelets following stimulation with ADP, showed shape change and some degree of centralization of the actomyosin gel. Affected platelets had comparable numbers of GPIIb/IIIa complexes and expressed comparable numbers of fibrinogen receptors as normal platelets in response to ADP. Cytoskeletal assembly in affected platelets was normal in response to PMA but incomplete in response to ADP and A23187. Failure of platelet aggregation in bleeding Simmental cattle is predicted to arise from abnormal cytoskeletal assembly following calcium mobilization and phosphorylation of myosin light chain in response to ADP. PMID- 8191407 TI - Heparin-associated thrombocytopenia: isolation of the antibody and characterization of a multimolecular PF4-heparin complex as the major antigen. AB - Sera of 34 patients with heparin-associated thrombocytopenia (HAT), giving a positive result in the serotonin release assay (SRA), were assessed in a platelet factor 4 (PF4)/heparin ELISA. Three sera revealing indeterminate results in the SRA and 10 control sera were also investigated. Both tests correlated closely (Kappa 0.742; p = 2.67 x 10(-7)), but one positive serum in the SRA was negative in the pF4/heparin ELISA. We have isolated the HAT antibodies by absorbtion and elution of HAT sera using endothelial cells (HUVEC). Eluates gave similar results as the sera in the PF4/heparin ELISA (Kappa 0.837, p = 9.26 x 10(-9)), and they also correlated very closely with the SRA (Kappa 0.888; p = 8.89 x 10(-10)). This demonstrates that HAT antibodies bind to the same epitope on platelets and on endothelial cells. High heparin concentrations released PF4 in a dose dependent manner from microtiter plates if PF4/heparin, but not if PF4 alone, was covalently linked. Concomitant to the release of PF4, binding of HAT antibodies to PF4/heparin decreased, as indicated by the median optical density (OD) values of OD 0.88 in the presence of buffer compared to OD 0.181 in the presence of 100 IU/ml heparin. The latter values were similar to those obtained when plates were coated with PF4 alone (median OD 0.203). Binding of three eluates was not inhibited by high heparin concentrations and they reacted also with PF4 alone. We conclude that multimolecular PF4/heparin complexes represent the major antigen in HAT. These multimolecular complexes might present several epitopes and form immune complexes after HAT antibody binding which activate platelets via the FcRII. In a few cases, PF4 alone can be recognized by the antibody. However, there is also evidence that other molecules might be involved in some patients. PMID- 8191408 TI - Experimental carotid thrombosis in the guinea pig. AB - The aim of our study was to develop a new carotid thrombosis model with an arterial shear rate close to that prevailing in affected arteries of patients with transient ischemic attacks (TIAs) and moderate carotid stenosis and to test various antithrombotic principles. In anaesthetized guinea pigs, carotid blood flow was monitored by a Doppler flow probe and the vessel was damaged by 2 or 3 brief pinches by a surgical forceps. The intravenous effects of aspirin (20 mg/kg), heparin (200 U/kg) and hirudin (500 micrograms/kg) or Ro 44-9883 (0.2 to 1 mg/kg), a new selective non-peptidic GP IIb-IIIa inhibitor were tested. After the damage, blood flow progressively decreased to zero and could regularly and reproducibly be restored by a mechanical shaking of the artery. The occlusive thrombus consisted mainly of platelet aggregates. The estimated shear rate in the damaged carotid artery was in the range of 1500 to 2800 s-1. The resulting cyclic flow variations (CFVs) were obtained in all the guinea pigs and were abolished in 10%, 20% and 60% of the animals treated with heparin, hirudin and aspirin, respectively. Ro 44-9883 abolished dose dependently the CFVs with 100% abolition at 1 mg/kg. Thus reproducible thrombosis without additional stenosis can be generated in the carotid artery of the guinea pig at a lower shear rate than that prevailing in the classical thrombosis models. GPIIb-IIIa blockade showed a higher curative efficacy than inhibition of the cyclooxygenase pathway or that of thrombin generation either through an antithrombin III dependent or independent mechanism. PMID- 8191409 TI - Inventory of exogenous hemostatic factors affecting the prothrombin activating pathways. For the Registry of Exogenous Hemostatic Factors of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. PMID- 8191410 TI - Anticoagulation during CABG in factor XI deficiency, a case report. PMID- 8191411 TI - Up-regulation of tissue factor mRNA in human umbilical vein endothelial cells by calmodulin inhibitor W7. AB - Tissue factor (TF) is an integral membrane glycoprotein that serves as a cofactor for the blood coagulation factor VIIa. The induction of TF synthesis and activity on the surface of endothelial cell membrane is initiated by lipopolysaccharide (LPS), phorbol 12-myristate 13-O-acetate (PMA), and inflammatory factors such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha). Treatment of cells with 1 micrograms/ml LPS induced an 8.7-fold increase in total TF activity compared with nontreated cells. Co-incubation with 1 micrograms/ml LPS and 30 microM W7, a potent calmodulin inhibitor, resulted an additional 2.0 fold increase in total TF activity. A similar tendency was observed after treatment with either TNF alpha plus W7, or IL-1 beta plus W7. The effect of W7 appeared to be synergistic since incubation with 30 microM W7 alone increased TF activity levels to only 1.5-fold that of control cells. Northern blot analysis showed that W7 and LPS-treated endothelial cells expressed about three times higher levels of TF mRNA compared to LPS-treated cells. Treatment with W7 and LPS resulted in a slow but large calcium influx into endothelial cells. This result suggest that the contribution of W7 may be dependent mainly on calcium influx by unknown mechanisms rather than direct inhibition of calmodulin, because calcium ionophore treatment also showed a synergistic effect on TF mRNA and activity expression. PMID- 8191412 TI - Increased plasma free gamma carboxyglutamic acid levels during deep vein thrombosis and intravascular disseminated coagulation. AB - Gammacarboxyglutamic acid (gla) is a non essential amino acid synthesized in presence of vitamin K, predominantly found in coagulation and bone proteins. In 14 cases of deep vein thrombosis and in 11 cases of disseminated intravascular coagulation, compared to 19 normal subjects and 9 patients hospitalized for leg pain, free plasma gla levels were found significantly elevated (respectively 372 +/- 244 and 559 +/- 361 versus 146 +/- 34 and 120 +/- 40 pmol/mL). In six paired plasma and serum, gla levels were similar. These results suggest an involvement of blood coagulation in gla generation with need of a catabolism of the activated factors. A significant decrease was noticed during vitamin K antagonist therapy and liver disease, both instances in which the synthesis of gla containing coagulation factors is affected. During hepatocellular carcinoma with elevated desgamma carboxyprothrombin, gla was found normal, denying an global impairement of the vitamin K metabolism. PMID- 8191413 TI - Novel factor Xa and plasma kallikrein inhibitory-activities of the second Kunitz type inhibitory domain of urinary trypsin inhibitor. AB - Urinary trypsin inhibitor is a glycoprotein with a structure in which two Kunitz type inhibitory domains are linked in a row. We isolated two genes encoding the 70 amino acid sequence from the 78th amino acid (Thr) to the C-terminal and the 68 amino acid sequence from the 80th (Ala) to the C-terminal of human urinary trypsin inhibitor, both which correspond to the second Kunitz-type inhibitory domain, and then constructed expression plasmids by ligating it to the E. coli alkaline phosphatase signal peptide gene. These plasmids under the control of the tryptophan promoter expressed the second domain in E. coli strain JE5505 which lacks the membrane lipoprotein. The recombinant second domain purified from the culture supernatant of the transformant inhibited trypsin, plasmin, leukocyte elastase and chymotrypsin which are known to be inhibited by urinary trypsin inhibitor. In addition it inhibited blood coagulation factor Xa and plasma kallikrein in a concentration dependent and competitive manner, and significantly prolonged the plasma-based activated partial thromboplastin time (APTT). The truncated natural counterpart obtained by a limited degradation of human urinary trypsin inhibitor also revealed the identical inhibitory activities. PMID- 8191414 TI - Anticoagulant therapy in deep venous thrombosis. A randomized controlled study. AB - Ninety patients with venographically proven deep venous thrombosis(DVT) but without clinical signs of pulmonary embolism(PE) were randomized into two different treatment regimens to compare the safety and efficacy of continuous intravenous heparin and oral anticoagulant(AC) treatment versus non-AC treatment. All patients in the two treatment groups were actively mobilized from the day of admission and wore graduated compressing stockings. In the non-AC-group the patients were treated with phenylbutazone for ten days. Treatment with heparin was maintained for 6 days and oral AC treatment was given from the third day and continued for 3 months. Venography was repeated after 30 days. A perfusion ventilation lung scan was performed on day 1-2, 10 and 60. In fifty-nine patients a revenography was performed, twenty nine in the AC-group and thirty in the non AC group. For distal veins regression was found in nine and eight respectively (4.4% in favour of AC, 95% confidence limit 27.5% to -18.7%) and in proximal veins regression was found in five and eight, respectively (10.9% in favour of AC, 95% confidence limit 32.0% to -10.1%). No difference in lung scans was found after 10 days (0.8% in favour of AC, 95% confidence limit 21.5% to -19.9%) or after 60 days (3.3% in favour of non-AC treatment, 95% confidence limit 21.8% to 28.5%). In the AC group the incidence of bleeding complications was 8.3%. No side effects of phenylbutazone was found. The present controlled clinical study demonstrated no effect of AC-treatment on DVT progression in actively mobilized patients wearing graduated compressing stockings when compared to a non-AC treated group receiving analgetic therapy with phenylbutazone. However, the patient population of the study is relatively small with wide confidence intervals for differences between groups. Before more general recommendations can be made, a large scale placebo-controlled study is needed to evaluate the possible effect of AC-treatment in DVT patients, who can be mobilized from the first day. PMID- 8191415 TI - Potential etiologic role of PAF in two major septic complications; disseminated intravascular coagulation and multiple organ failure. AB - A possible role of platelet-activating factor (PAF) in the occurrence of the two septic complications, i.e., disseminated intravascular coagulation (DIC) and multiple organ failure (MOF) was investigated, employing a rabbit model and a novel PAF antagonist E5880. By an instillation of fecal suspension into the common bile duct of the rabbit, manifestations of DIC and MOF were observed with high reproducibility by 9 hours after the septic insult. E5880 was intravenously administered to 12 rabbits for 1 hour after the septic insult at dose of 1 mg/kg (n = 6) or 3mg/kg (n = 6). All the rabbits were subjected to observation of vital signs and serial determination of laboratory tests for 9 hours and then lung, liver and kidney were removed for histological examination. Blood endotoxin level increased significantly by 9 hours after the septic insult. Although administration of E5880 did not affect the endotoxemia, the antagonist attenuated in a dose related manner laboratory manifestation of DIC such as thrombocytopenia and prolonged prothrombin time as well as that of MOF such as increase in serum bilirubin and creatinine level. The beneficial effect of E5880 on MOF was also confirmed by the histological evaluation. These observations indicated that PAF is deeply involved in the occurrence of DIC and MOF due to sepsis and E5880 may be one of the modalities to treat or prevent these two major septic complications. PMID- 8191416 TI - Fibrinogen and factor VII in male neonates. AB - Recent studies have suggested that retarded fetal and early growth predisposes to cardiovascular disease of males in adult life. This is partly explicable by an association between the haemostatic variables fibrinogen and factor VII and the placenta/birth weight ratio. Since many characteristics influence clotting factors during life, levels of fibrinogen and clotting factor VII were measured in cord blood of male neonates. The placenta/birth weight ratio did not correlate with the birth weight for gestational age and appeared to be only a minor indicator of fetal growth. These findings make it unlikely that the level of fetal outcome 'programmes' male neonates via fibrinogen or factor VII to develop cardiovascular disease in adult life. PMID- 8191417 TI - The reliability of Hickman catheter blood for the assessment of activation markers of coagulation and fibrinolysis in patients with hematological malignancies. AB - We studied the reliability of Hickman catheter (HC) blood for the determination of activation markers of coagulation and fibrinolysis in 14 patients with hematological malignancies. 10 of 22 HC samples were contaminated with heparin, probably as a consequence of our institutional antithrombotic catheter care, and withdrawn from statistical analysis. Prothrombin activation fragment F1.2, thrombin-antithrombin III complexes, soluble fibrin, degradation products of fibrinogen and fibrin, total degradation products, alpha 2-antiplasmin and antithrombin III levels withdrawn from Hickman catheters did not differ significantly from peripheral venous blood samples. Fibrinogen levels were slightly but significantly higher in peripheral venous blood samples. We conclude that Hickman catheter blood gives reliable results for the determination of activation markers of coagulation and fibrinolysis in patients with hematological malignancies, but may be less useful in clinical practice due to frequent heparin contamination. PMID- 8191418 TI - Basic fibroblast growth factor suppresses tissue plasminogen activator release from cultured human umbilical vein endothelial cells but enhances that from cultured human aortic endothelial cells. AB - Since basic fibroblast growth factor (bFGF) modulates the functions of vascular endothelial cells, we hypothesized that this factor may be involved in the regulation of the blood coagulation-fibrinolytic system mediated by the cells. Confluent cultures of vascular endothelial cells from human umbilical vein were treated with recombinant human bFGF (bFGF) in a serum-free medium and the content of tissue plasminogen activator antigen (t-PA:Ag) in the medium was determined by EIA. Treatment with bFGF resulted in a significant decrease in the release of t PA:Ag from the cells accompanied with a less t-PA activity in the medium. In contrast, the t-PA:Ag release from human aortic endothelial cells was significantly increased by bFGF. The bFGF-induced decrease in the t-PA:Ag release from the venous endothelial cells was completely blocked by anti-bFGF antibody. The incorporation of [3H]leucine into the acid-insoluble fraction of the cells was significantly increased by bFGF; however, the activity of lactate dehydrogenase leaked into the medium was significantly decreased, suggesting that the suppression of the t-PA:Ag release caused by bFGF in the venous endothelial cells was not due to either a nonspecific inhibition of protein synthesis or a nonspecific cell damage. Since bFGF is postulated to be released from damaged endothelial cells, the present data suggest the regulation by bFGF of hemostasis mediated by endothelial cells when the vascular endothelium was damaged. PMID- 8191419 TI - Serotonin modifies the endothelial turnover-inhibiting activity of heparan sulfate. PMID- 8191420 TI - [How to gain a foothold in the media storm?]. PMID- 8191421 TI - [Research on musculoskeletal diseases--the ugly duckling?]. PMID- 8191422 TI - [Bone marrow transplantation--a constantly developing procedure--requiring updating]. PMID- 8191423 TI - [Use and misuse of naloxone at departments of obstetrics in Norway]. PMID- 8191424 TI - [Administration of naloxone to newborn infants at obstetric departments in Norway]. AB - Recommendations for the dosage of naloxone to reverse opiate depression in neonates were revised by the American Academy of Pediatrics in 1989. In order to ascertain the extent to which these new recommendations have been implemented in Norway, we sent questionnaires to the maternity centres by mail. The responses from 60 different centres covered 88% of the total births in Norway in 1991. The dosages of naloxone used varied from 0.01-0.1 mg/kg, and the reported frequency of use in newborns varied between < 10-50%. Similarly, the use of opiate analgesia in parturients varied considerably, with frequencies ranging from < 10 to 90%. We conclude that there is wide variation in use of naloxone to treat neonates in Norway and in the prescribed dose, and suggest that most centres should re-evaluate the dose. Some centres also need to re-evaluate the rate of usage. PMID- 8191425 TI - [Erythema infectiosum in pregnancy. A follow-up of children after 2 years]. AB - During an epidemic of erythema infectiosum in Norway 1984-86, infection with human parvovirus B19 was diagnosed in 22 pregnant women by detection of specific IgM antibodies. Information about the outcome of pregnancy was obtained in 19 cases. 17 women delivered live babies. In two cases, spontaneous abortion occurred in week 16 of the pregnancy. In 11 cases, cord blood and serum samples were obtained from the children at an age of between six and 15 months. No specific IgM antibodies were found in cord blood. Clinical information on 16 children at two years of age revealed normal growth and development in 15 cases. One child was hyperactive and showed delayed language development. B19 IgG antibodies were detected in three children with normal growth and development. According to our findings, there was no association between infection with human parvovirus B19 in pregnancy and congenital abnormalities. PMID- 8191426 TI - [The TORCH study. A reevaluation]. AB - The TORCH panel is used to screen for congenital infection. The purpose of this study was to evaluate the use of TORCH by pediatricians and pediatric trainees in a university pediatric department. The patient charts corresponding to the 109 samples submitted to the Institute of Bacteriology from 1987-91 were reexamined for evidence suggestive of congenital infection. Generally, the charts contained little information that might explain the reason for ordering a full TORCH panel. None of the submitted samples yielded conclusive evidence of congenital infection. TORCH studies appeared to have been requested on very liberal indications. We conclude that the TORCH panel as used at present creates a lot of work for microbiologists, but yields little information. A more targeted approach to testing for congenital infection seems called for. PMID- 8191427 TI - [Use of acetylsalicylic acid and other antiphlogistics in hematemesis/melena]. AB - The use of acetylsalicylic acid and other non-steroidal, anti-inflammatory drugs was studied prospectively in 207 patients admitted for suspected upper gastrointestinal bleeding. In addition to detailed drug history, plasma samples for drug analyses were obtained from the majority of the patients. 64 of the patients admitted recent intake of ulcerogenic drugs, and the plasma samples revealed another 11 users. Acetylsalicylic acid was the most prevalent substance, but all available non-steroidal, anti-inflammatory drugs were represented in the material. Gastroduodenal ulcers were found in 94 (44%) of the patients; two thirds of the users and one third of the non-users. Gastric ulcer was slightly more prevalent than duodenal ulcer in both groups. Six patients with drug associated bleeding had previously had a verified drug-associated ulcer. Only 12 users and 16 non-users denied dyspeptic complaints before admission. The users were older, they generally had a lower Hgb on admission than non-users had, and a slightly higher transfusion requirement, but these factors did not result in significant differences as to clinical outcome. The drug analyses of plasma samples showed a discrepancy to the anamnestic data in 25% of the patients and may be a useful addition to drug history in these studies. PMID- 8191428 TI - [The Pipelle. A good instrument for histological endometrial diagnosis]. AB - The pipelle is a device for collecting tissue from the uterine cavity, thereby also allowing morphological assessment of the endometrium, such as cyclus stages and hyperplasias. The biopsy is taken without use of anaesthetics and is a rapid and simple procedure. We have compared the Pipelle with the Endocyt device in 50 women and conclude that the pipelle method is just as simple to perform as the endocyt method and is tolerated just as well. The pipelle method represents an alternative to diagnostic curettage and deserves to be used more extensively. PMID- 8191429 TI - [Transplantation immunology in allogeneic bone marrow transplantation. The significance of HLA-tissue crossmatching between donors and recipients]. AB - We describe our current programme for donor-patient HLA matching. First, the patient and family members are serologically typed to define HLA haplotypes and to search for HLA genotypically identical siblings. If no HLA identical siblings can be found, we search for a haploidentical family donor with zero or at most one HLA molecule mismatch on the non-shared haplotype. Secondly, we search for an HLA identical unrelated donor in the Norwegian and foreign bone marrow donor registers. For final matching of patient and unrelated or haploidentical donors, we include genomic typing of DRB1, DQB1, and DPB1 alleles by sequence-specific oligonucleotide probing or direct sequencing. PMID- 8191430 TI - [Musculoskeletal complaints in a population. Occurrence and localization]. AB - Musculo-skeletal complaints are widespread. In a population survey in Ullensaker, a local community 40 kilometers north-east of Oslo, only 15% reported no musculo skeletal symptoms during the last year. Just as many, 15%, predominantly women aged 50-70 years years, reported having such symptoms every day during the last year. 53% reported that they had experienced low back pain during the last year. The corresponding figures for headache, neck symptoms and shoulder symptoms were 49%, 48% and 46% respectively. Headache was most common among the younger women and neck and shoulder symptoms among middle-aged, while hip and knee symptoms were most frequent in the elderly women. Women in all age groups reported symptoms from more parts of the body than the men did. PMID- 8191431 TI - [Oxidative stress and antioxidants]. AB - Oxidative stress is a metabolic state where the cellular oxidative reactions are out of control. Under such conditions superoxide (O2.-) may accumulate, leading to formation of the hydroxyl radical, OH.. This is a free radical that abstracts hydrogen from the double bonds of unsaturated fatty acids. The fatty acid will then become a free radical which reacts easily with oxygen to form a peroxyradical. This will in turn abstract hydrogen from another fatty acid, establishing a perpetuating oxidative chain reaction. This may lead to peroxidation of cellular functions. DNA, proteins and carbohydrates may be oxidized too. There is good evidence that oxidative stress may play a role in the pathogenesis of cancer, atherosclerosis, ischemic tissue damage and inflammatory diseases. Possibly antioxidants can be used to limit oxidative stress. Recent reports indicate that high intake of vitamin E is associated with reduced risk of coronary heart disease. PMID- 8191432 TI - [Metabolic acidosis--a diagnostic challenge]. AB - Metabolic acidosis can be caused by a variety of pathological conditions, but intoxication with ethylene glycol or methanol should be suspected in cases of a combined increase of osmolal and anion gaps. The determination of the gaps is based on readily available laboratory tests, and the results is known soon after the blood sample is taken. This procedure is of particular interest for hospitals where specific analyses for methanol and ethylene glycol are not available, since calculation of the gap can give an early indication of what treatment to use. Therefore, the gaps should be calculated as a routine in patients with metabolic acidosis of unknown origin. The authors describe the principles for calculating and using the gaps, and report three cases which illustrate their usefulness in practice. PMID- 8191433 TI - [Cervical cytological tests among female general practitioners. A study of health habits of physicians]. AB - The authors present results from a study which focused on physicians' own routines for health controls, using pap-smear screening as example. The study was designed as a survey where a questionnaire was mailed to all Norwegian female general practitioners (720). The response rate was 95%. Half of the informants had a pap-smear taken according to the official recommendations. Of the remainder, just as many had a routine pap-smear taken more often than recommended as less often than recommended. The reported routines are closer to the official recommendations than they are for other women. Half of the informants reported that, as physicians, they found it more difficult for them than for other women to have a routine pap-smear taken. The authors discuss aspects which could motivate female general practitioners to comply themselves with the recommended screening program. The results are also relevant for the planning of a special health service for physicians. PMID- 8191434 TI - [Information routines in HIV screening of pregnant women]. AB - HIV-antibody testing has been carried out as a routine among pregnant women in Norway since September 1987. Up to September 1991 (later information is incomplete) 339,823 women have been tested. 25 of these were positive. In this survey we interviewed by questionnaire 55 physicians and nurses who had been asked for a second blood sample from their patients. None of the physicians who had tested the 25 HIV-positive women were included. Among these 55, nine stated that the women had suffered psychological distress after the second testing, and one reported that the woman in question had chosen to have an abortion. The study demonstrates possible opportunities for improving the handling of information, both between laboratories and physicians/nurses and between physicians/nurses and the women who are asked to give a second blood sample. We also interviewed 290 physicians who had asked for a HIV-test for pregnant women but had received no false positive results (the number of respondents was 258). Among a total of 379 physicians and nurses, one third stated that they seldom or never asked explicitly if the woman wanted to be tested. 88% were in favour of routine testing and 97% reported a positive or very positive attitude among the pregnant women towards screening. Nearly one third stated that they had insufficient knowledge about the significance of a false positive test result. PMID- 8191435 TI - [Mass screening for cervical cancer. A one-year registration of cervical cytological tests]. AB - In 1990 the Norwegian Ministry of Health and Social Affairs decided to start an organised screening programme for cervical cancer. All women aged 25-70 years will be offered screening every three years. During the first three years of the programme, all spontaneous screening in Norway is to be reported to a central unit located at the Cancer Registry of Norway. A pilot project has been implemented in the counties of Sor-Trondelag and Vestfold to evaluate the organisational aspects of the screening programme. A total of 509,641 smears were recorded during the first year of recording. The majority of smears were taken from women below 50 years. Most smears (88.6%) had normal tissue morphology, while 2.9% displayed various cellular changes. Smears from younger women showed the highest rate of Human papillomavirus (HPV) changes and mild (CIN 1) and moderate (CIN 2) dysplasias, whereas the rated malignant cellular changes was highest in the older age groups. The findings support the wide age range of the target group. PMID- 8191436 TI - [External fetal version in breech presentation]. PMID- 8191437 TI - [Use of condoms prevents sexually transmitted diseases]. PMID- 8191438 TI - [A new steering instrument. DRG-weighting of waiting lists]. PMID- 8191439 TI - [Before the big battle: the debate about a health reform in the USA]. PMID- 8191440 TI - [When something goes wrong]. PMID- 8191441 TI - [Is disease a sole criterion for rationing of security? An attempt to discuss the basic question in social policy]. PMID- 8191442 TI - [Reduced risk of cancer in total alcohol abstinence]. PMID- 8191443 TI - [Bacterial conjunctivitis]. PMID- 8191444 TI - [Oral contraceptives as postcoital prevention--time to withdraw the requirement of prescription?]. PMID- 8191445 TI - [Alcohol and risk of breast cancer. Studies published between 1988 and 1993]. AB - Epidemiological studies have suggested that moderate intake (1-2 drinks per day) of alcohol may increase the risk of breast cancer by more than 50%. A relatively large proportion of women in many countries consume alcohol at this level, and a precise assessment of the related breast cancer risk is therefore important. In this paper we have reviewed all published studies subsequent to a comprehensive meta-analysis on alcohol and breast cancer, published in 1988. Among four cohort studies, the relative risk of breast cancer associated with 1-2 drinks per day (compared with no drinking) varied between 1.0 and 1.3, and the null value of 1.0 was included in the 95% confidence interval for each of the studies. For consumption higher than two drinks per day, two of the four cohort studies indicated a significantly increased risk. Among 14 case-control studies, the point estimates showed increased breast cancer risk in 11, and five were statistically significant. Three studies indicated a negative association, but the confidence interval included 1.0 in two of them. Among case-control studies which provided information on intakes higher than two drinks, eight out of 13 studies showed a statistically significant positive association. Collectively these studies support a weak positive association between moderate consumption of alcohol and breast cancer risk. The tendency between studies is consistent, but the precision of the estimate of relative risk is low in most studies. Unless consumption is two drinks or higher per day, no recommendation to reduce drinking should be made based on the present evidence relating alcohol consumption to breast cancer risk. PMID- 8191446 TI - [Primary treatment of locally advanced breast cancer with neoadjuvant chemotherapy]. AB - Since February 1991, in Health Region 3, patients with recently diagnosed Stage III breast cancer have been treated with neoadjuvant chemotherapy. This treatment includes 16 weeks of chemotherapy prior to local treatment, usually consisting of mastectomy and postoperative radiotherapy. 48 patients have so far undergone this treatment. The majority (43 patients) received chemotherapy consisting of weekly doses of Adriamycin. Even with a high average age the therapy has been well tolerated. 60% of the patients partially responded to the therapy, an additional 15% experienced minimal response. At this point it would be premature to evaluate the long term effect of the therapy. It is very interesting, however, that at this stage we have not observed any local recidive in patients who showed primary response to chemotherapy. Following primary treatment of this group of patients, local recidive is usually a frequent and early observation. PMID- 8191447 TI - [Chloramphenicol eyedrops in acute bacterial conjunctivitis. A comparison of 2 dosage regimes in general practice]. AB - Acute bacterial conjunctivitis is a prevalent infection in the population. Topically applied chloramphenicol has been the most frequently used treatment on this indication. The recommended dosage of 0.5% eye drops has been one drop hourly/every two hours for three days, thereafter every 4-6 hours. This dosage is not based on scientific documentation. We have conducted a clinical trial in general practice to compare the standard dosage with a simplified dose regimen. 77 patients were allocated to the regimen described above and 75 patients were instructed to use the drops four times a day. Mean duration until complete healing of all symptoms was 4.4 days (median 4; 95%-confidence interval (CI) 4-5) and 4.8 days (median 5; CI 4-5) in the two groups. The proportion of completely cured patients after nine days of treatment was 95% and 88% respectively; after four days corresponding percentages were 61% and 44% (p < 0.05). For other clinical variables the differences were small and not statistically significant. Compliance was significantly better for the simplified regimen (p < 0.001). The study indicates that the simplified dose regimen may be preferable in clinical practice. PMID- 8191448 TI - [Follow-up of chronic inflammatory bowel disease. A 10-year material]. AB - During a ten year period, all patients (N = 641) with chronic inflammatory bowel disease were systematically followed, clinically and endoscopically by means of mucosal biopsies. The complexity of these disorders was obvious, and in 103 patients it was impossible to establish a diagnosis of either ulcerative colitis or Crohn's disease. Fulminant colitis occurred in 9.8% of the ulcerative colitis patients and only four of these had to have surgery. Total colectomy was necessary in only 58 patients. Twenty-one patients died, four from causes related to the inflammatory bowel disease. Six patients with ulcerative colitis were treated for adenocarcinoma of the colon. No malignancies were found in the patients with Crohn's disease. The biopsies showed only two patients with high grade dysplasia. PMID- 8191449 TI - [Indirect genetic diagnosis of cystic fibrosis]. AB - The diagnosis cystic fibrosis was made in a three years old girl. Her older brother and her mother's sister both had minor symptoms and signs suggestive of this disease. None of 17 mutations in the gene locus for cystic fibrosis was identified in the patient by DNA-analyses. By haplotype analyses her brother, but not her aunt, was shown to share the proband's haplotypes. This family is used as an example of the general diagnostic potential of indirect diagnosis of genetic disease by haplotype analysis. The prerequisite for haplotype analysis is the availability of DNA from both the patient and the patient's relatives, stressing the need for a DNA bank of material from persons with inherited disorders, for future use. PMID- 8191450 TI - [Evaluation of the rotator cuff with magnetic tomography]. AB - Rotator cuff tears are difficult to diagnose clinically, both in the acute and the chronic phase. Both conservative and surgical treatment give the best results if the injury is detected early. Magnetic resonance imaging (MRI) has recently been introduced for diagnoses of cuff tears. The purpose of this study was to establish the accuracy of MRI in relation to surgical findings in the same patient group. MRI was used in the diagnosis of 25 patients who later underwent surgery for injury to the rotator cuff. During the surgery, 19 total tears were identified, of which 15 had been described by MRI. MRI showed a sensitivity of 79% and a specificity of 83%. The predictive value of a positive test was 83%. In experienced hands, MRI is extremely accurate for detecting rotator cuff injuries, but ultrasonography should still be the first method of diagnosis in Norway, because of its accuracy when used by experienced practitioners, and its availability and low cost. PMID- 8191451 TI - [Connections between musculoskeletal complaints and personality]. AB - Modern research has demonstrated a weak association between level of muscle tension and experience of muscle pain. Anxiety and dysphoric over-responsiveness are the traditional psychogenic risk factors in muscle tension. Results from recent Norwegian research lend support to a more multidimensional causal understanding of muscle tension and of pain. Generally, personality factors were found to be a contributory cause of muscle pain of the neck and shoulders, whereas ergonomic load was found to be of greater significance for low back pain. Personality factors may induce patterns of skeletal muscle activation discrepant with characteristics of the skeletal muscle physiology: Preference for aerobic activities may develop through social learning, whereas the muscles may be genetically biased toward anaerobic activities. Furthermore, personality factors may be challenged by the work setting, and may result in mismatch that provokes muscle pain. Impatient expenditure of effort has appeared as a mediating personality risk factor among workers exposed to high ergonomic load, whereas dysphoric over-responsiveness mediated back pain primarily among staff exposed to high emotional load. PMID- 8191452 TI - [Prokinetics in reflux disease. Action mechanisms and clinical effects]. AB - Gastro-oesophageal reflux disease is a primary motility disorder of the upper gastro-intestinal tract, with varying degrees of disturbed lower oesophageal sphincter function, disturbed peristalsis of the oesophageal body and delayed gastric emptying. Traditional treatment has focused on "detoxifying" the refluxate by suppressing gastric acid secretion. With the advent of cisapride (Prepulsid), prokinetic drugs offer a possibility of influencing the underlying motility disturbances without causing the serious side effects of earlier prokinetic drugs. It seems to be well documented that cisapride is useful in both the short-term and the long-term treatment of grade 1 reflux oesophagitis, and also in more severe cases as part of combination regimens involving acid suppressive drugs. PMID- 8191453 TI - [Medical coding and classification systems]. AB - Medical coding and classification systems are expected to become increasingly important in the health care sector. Together with and as an integrated part of the electronic health information systems, the coding and classification systems will be used to improve the quality and effectiveness of the medical services. Activities connected to the different coding and classification systems are a very important component of the attempts at standardization taking place both in Norway and in the rest of Europe within the discipline medical informatics. These activities must be secured a proper professional and economic foundation. It is also of vital importance that national health authorities should participate in these activities and establish formal cooperation with professional bodies. In Norway, the Ministry of Health and Social Affairs has accepted with some miner modifications, our suggestion for a model where the Norwegian Medical Association would be responsible for the medical aspects of the coding and classification systems and for their development, and the Norwegian Centre for Medical Informatic's for organization, distribution, electronic version, integration in information systems and user assistance. PMID- 8191454 TI - [Alcohol related mortality 1980-90, how many children are affected?]. AB - During the decade 1980 to 1990, 3,500 persons in Norway, under 30 years of age lost their mother or father as a result of an alcohol-related disease. Many of these persons were small children. The article presents research based on linkage of data from the population census of 1980, causes of death and the population register. The results show large regional differences in the rates of children who lost a parent due to misuse of alcohol. Even larger differences were observed between the different districts within the city of Oslo. Differences in registered sales and the consumption of illicitly distilled alcohol both help to explain the regional differences between counties. PMID- 8191455 TI - [Diet and cancer risk]. AB - Reduction in the incidence of competing diseases will steadily increase the relative importance of cancer as a cause of death. A curative break-through has occurred for some, but definitive solutions in the treatment of a majority of cancers remain undiscovered. Attempts at primary and secondary prevention have been encouraging in some areas, but progress is slow, and suggests that the search for causes of cancer should be intensified. It has been estimated that between 30% and 60% of all cancers may be attributable to dietary factors. The main hypothesis has suggested that intake of animal fat increases the risk. This hypothesis has been extensively tested, especially in relation to cancer of the breast and colon, and ecological studies, which have correlated use of dietary fat with incidence or mortality between countries, have confirmed the hypothesis. For cancer of the colon, it has also been verified in case-control and cohort studies, but analytical epidemiological studies have failed to show a consistent positive association between dietary fat and risk of breast cancer. Simultaneously, dietary factors with protective potential have received increasing attention. An overview of all studies which have investigated the relation between dietary fruit and vegetables and the risk of cancer showed a highly consistent protective effect, indicating that fruit and vegetables may provide general protection against cancer. Maybe the search for a "magic" protective factor is blocking this already documented insight, which suggests that daily intake of five servings of fruits or vegetables may have a strong and consistent protective effect on risk of cancer. PMID- 8191456 TI - [Violence--a field for preventive health work]. PMID- 8191457 TI - [Treatment of rheumatic patients in the South]. PMID- 8191458 TI - [The Norwegian version of ICPC]. PMID- 8191459 TI - [Why have certain groups of physicians lost their patients' confidence?]. PMID- 8191460 TI - [Should hospitals be managed according to the principles of private sector economics?]. PMID- 8191461 TI - [Furor sanandi--a reflection over the passion to heal]. PMID- 8191462 TI - [Sunbathing and malignant melanoma]. PMID- 8191463 TI - [Drug economics--a potent cure, but with the risk of adverse effects]. PMID- 8191464 TI - [Peptic ulcer. Reduced surgical needs due to pharmacological progress]. PMID- 8191465 TI - [Etiological and pathological aspects of malignant melanoma]. AB - The incidence of malignant melanoma has increased markedly in recent years in Norway, and in other countries. Epidemiologic studies show that important risk markers are familial occurrence, skin type, number of regular nevi and presence of dysplastic nevi. The ultraviolet component of sunlight is an important etiologic factor, especially acute intermittent sun-burn experienced during childhood. Some of the melanomas are familial, and genetic markers can perhaps be used in screening. Finally, health education is a very important tool in reducing incidence of melanoma and mortality from this disease. In each single patient, data from cellular and molecular research can assist in making a precise diagnosis and in estimating prognosis. PMID- 8191467 TI - [Self-reported fibromyalgia among women aged 36-55 years]. AB - In a mailed questionnaire to a sample of Norwegian women 36-55 years of age, 4.4% reported having fibromyalgia. Women with fibromyalgia often had multiple health problems. Compared with other women, more of them reported nervousness, migraine and tiredness. They had many consultations with medical practitioners, but were also frequent users of alternative medicine. Recovery from fibromyalgia was seldom reported. Women with fibromyalgia had especially poor self-rated health status. Many were receiving a disability pension, and the proportion of exists from the labour market was clearly higher among women with fibromyalgia than among women with other chronic diseases. As in the case of many other long lasting diseases the prevalence of fibromyalgia was somewhat higher in lower than in higher socio-economic groups. PMID- 8191466 TI - [Surgical treatment of gastrointestinal malignant melanoma]. AB - Malignant melanoma is the most common metastatic lesion of the intestine, found at autopsy in approximately 60% of patients who die from melanoma. Common symptoms include bleeding, perforation and ileus/subileus. Patients with such symptoms should be operated on immediately, if they are not too reduced because of advanced disease. Long-term survival (five years) has been achieved in 34 of 179 (19%) of stage IVA melanoma patients after a radical operation procedure. Surgical removal of gastrointestinal metastases provides effective palliation in 80-95% of patients, who undergo laparotomy. We describe two patients with gastrointestinal metastases from malignant melanoma. A 33 year-old man had a large melanoma metastasis removed (non-radically) from the small intestine. He recovered rapidly, and experienced good palliative effect for three months, but died from a recurrence of the disease six months after operation. The other patient had a melanoma metastasis in the right lobe of the liver, which was treated by right hemihepatectomy. There has been no recurrence ten months after operation. We recommend surgical removal of abdominal melanoma metastasis if the surgery can be performed without unacceptable risk. PMID- 8191468 TI - [Roboratio or relaxatio? Clinical theory and practice in the 19th century]. AB - The first Norwegian medical school was founded in 1814. Niels Berner Sorenssen (1774-1857), one of three professors, was responsible for teaching pathology and therapy, and for clinical education. Together with his student and successor, Andreas Christian Conradi (1809-68), he made his mark on Norwegian physicians for a period of 50 years. A few years ago a small handwritten book by a medical student, dated 1828, turned up in a second-hand market. This book, which contains notes from Professor Sorenssen's lectures on therapy, demonstrates that his teaching was heavily influenced by the speculative theories of John Brown (1735 88). Similar influence is traceable in the annual reports from Norwegian physicians during the second half of the 19th century. Sorenssen urged his students to thoroughly investigate the medical history and make a detailed clinical examination, and his attitude to therapy was careful, almost reluctant. This personal clinical attitude was probably more important than the theoretical foundation upon which he based his lectures. PMID- 8191469 TI - [Occupational and individual risk factors of muscular pain]. AB - It is suggested that occupational exposure to muscle load should be described by three factors to indicate health risks: level, repetitiveness and duration. A reduction in level is beneficial if the level is high (> 10-15% MVC). However, even a low level involves risk of musculoskeletal complaints if the exposure is repetitive. A reduction of the occupational exposure from 7-8 hours to 4-5 hours per day delays the development of musculoskeletal complaints, but does not provide long-term reduction of risk with frequent repetitions. When interventions are carried out to reduce the risk of occupational musculoskeletal complaints, it is necessary to consider psychosocial and individual constitutional factors in addition to the three factors constituting the occupational exposure to muscle load. PMID- 8191470 TI - [Muscle tissue for diagnosis of neuromuscular diseases. Procedures of specimen taking, transport and preparation]. AB - In this review we describe surgical methods for open muscle biopsy. In order to obtain optimal tissue quality, correct handling of the muscle specimens at all stages of the procedure is essential. A technologist who is familiar with the procedure should be present in the operating room. This is important to ensure that specimens for histochemical or biochemical studies are frozen immediately and specimens for electron microscopy are fixed without delay. We describe procedures for processing the specimens for cryostat sections, paraffin sections and electron microscopy, and a simple method for handling muscle specimens in local hospitals before transfer to a hospital with a neuropathological service. PMID- 8191471 TI - [Alternatives of drug therapy in Helicobacter pylori infections]. AB - The last three years of research on treatment of Helicobacter pylori infection support the recommendations made by the Working Party, World Congress of Gastroenterology 1990. Meta-analysis shows a noteworthy difference between the recommended regimens favouring the combination of bismuth, metronidazole and tetracycline. No regimen without bismuth has been shown to have a sustained Helicobacter pylori eradication rate exceeding 90%, nor has any alternative regimen been shown convincingly to stem the adverse effects without loss of efficacy. No serious adverse effects have been reported after following the current recommendation of bismuth medication. The highest reported Helicobacter pylori eradication rate according to "intention to treat" approximates 90%, which was obtained using bismuth subnitrate, metronidazole, and oxytetracycline. PMID- 8191472 TI - [Is UV-A a cause of malignant melanoma?]. AB - The first action spectrum for cutaneous malignant melanoma was published recently (2). This spectrum was obtained using the fish Xiphophorus. If the same action spectrum applies to humans, the following statements are true: Sunbathing products (agents to protect against the sun) that absorb UV-B radiation provide almost no protection against cutaneous malignant melanoma. UV-A-solaria are more dangerous than expected so far. If people are determined to use artificial sources of radiation for tanning, they should choose UV-B-solaria rather than UV A-solaria. Fluorescent tubes and halogen lamps may have weak melanomagnetic effects. Ozone depletion has almost no effect on the incidence rates of CMM, since ozone absorbs very little UV-A radiation. Sunbathing products which contain UV-A-absorbing compounds or neutral filters (like titanium oxide) provide real protection against cutaneous malignant melanoma, at least if they are photochemically inert. PMID- 8191473 TI - [Coenzyme Q10 (ubiquinone) in the treatment of heart failure. Are any positive effects documented?]. AB - Coenzyme Q10 is an endogenous substance which has a well established role as electron carrier in the mitochondrial synthesis of adenosine triphosphate (ATP). In addition, coenzyme Q10 also has antioxidant and membrane stabilizing properties. Based on biopsy samples from patients undergoing cardiac surgery and blood samples from patients with congestive heart failure, the existence of a relative Q10 deficiency in patients with cardiac failure has been suggested. A total number of eight double blind, placebo controlled studies in patients with heart failure have been published. Most of these studies include a small number of patients, and various methodological problems have been attributed to these. The results, judged as improvement in ejection fraction or work capacity, are inconsistent. In one large study, coenzyme Q10 was found to have a positive effect on morbidity, and in another on quality of life. However, although some of the results appear to be promising, more studies are needed, including studies designed with mortality as a primary end point, before the effect of the substance in patients with heart failure can be established. PMID- 8191474 TI - [A table for converting ICD-9 to ICPC. A common platform for health insurance statistics for primary health care and hospitals, outpatient clinics and specialists' practices]. AB - In 1992 Rikstrygdeverket decided that the analysis of billing systems and certificates of illness issued by the primary and secondary health care services should be based on ICPC. All general practitioners are expected to use ICPC codes. Doctors working in hospitals and other specialists have already used the ICD-9 classification for many years and did not want to have to use two different encoding systems. To obtain a common platform for statistical analysis, a referral system was necessary to convert ICD-9 codes to corresponding ICPC codes. In this article, the head of project discusses the material and methods used in this project, and summarizes the results and the structure and formats of the referral table. The author also briefly discusses the potentials and limitations when diagnostic codes are converted from ICD-9 to ICPC. PMID- 8191475 TI - [Economical evaluation of drugs. A steering method for the pharmaceutical sector of the 1990's?]. AB - Pharmaceutical products are important welfare goods both to individuals and to societies. Political authorities in Norway have high ambitions: pharmaceutical products should be of the best quality and available to people independent of their financial means. However, decreased economic growth, an increasing proportion of the health care needed by the elderly and accelerating developments in the medical field have led to a closer scrutiny of prices, costs and the extent of the public sector's responsibility in different parts of the health care system. Economic evaluation of pharmaceuticals is a supplement to the extensive and expensive clinical evaluations that have been going on for many years in the pharmaceutical industry. Information on cost-effectiveness of new products has internationally become more important and is needed in connection with subsidizing, prescriptions and distribution of drugs. The purpose of this article is to show how economic evaluation of pharmaceuticals could be used to increase efficiency in the Norwegian drug sector. The article also suggests how public guidelines could be established and how economic evaluations should be used, and considers the organisational consequences for the public sector. PMID- 8191476 TI - [Monoclonal antibodies against endotoxin in septicemia. Marketing or scientific evaluation?]. PMID- 8191477 TI - [Diagnosis--a product of cooperation with social consequences]. PMID- 8191478 TI - [The final hour--some thoughts on the "ars moriendi" motif. Death and eternal salvation]. PMID- 8191479 TI - [Open readmission. Seen from the general practitioner's point of view]. PMID- 8191480 TI - [Natural or synthetic surfactant in the treatment of neonatal respiratory distress syndrome]. PMID- 8191481 TI - [Information--most of the patients are satisfied]. PMID- 8191482 TI - [Violence--a field of concern?]. PMID- 8191483 TI - [Practical skills in general practice]. PMID- 8191484 TI - [Stunning of slaughtering animals on the farm]. AB - Recent changes in the Inspection Regulations have made it possible for practising veterinarians to stun and bleed animals on the farm. The Health and Welfare Law stipulates, amongst other things, that it is not permissible to put the welfare of the animal to disadvantage. Mechanical methods are the most suitable for use on farms, and of these methods the humane (cattle) killer is clearly to be preferred. The humane killer should be placed frontally, where the imaginary lines between the eyes and ears cross, or occipitally above the brain. A firearms license is needed. As many practising veterinarians are not experienced in the stunning and bleeding of animals, it is advised that these actions be left to emergency butchers. PMID- 8191485 TI - [Do you sometimes have a stitch loose too?]. PMID- 8191486 TI - [Zoonoses as a public health problem]. PMID- 8191487 TI - [Vaccination recommendation for Aujeszky disease]. PMID- 8191488 TI - [What is your diagnosis? Cow in calf. An emphysematous calf]. PMID- 8191489 TI - [Predecessors: veterinarians from earlier days (3). Vegetius]. PMID- 8191490 TI - Organizational and business issues affecting integrated delivery systems. AB - This chapter discusses the nature of an integrated system, the reasons for developing an integrated delivery system, and various organizational structures that might be used. The chapter then identifies several of the critical business issues affecting the development of an integrated system. PMID- 8191491 TI - Nonprofit medical care foundations. PMID- 8191492 TI - Management services organizations. AB - This chapter defines a management services organization (MSO), and discusses the goals and objectives of hospitals and physicians in creating an MSO and the advantages and disadvantages of an MSO. It stresses the necessity of developing a business plan in the formation of an MSO and discusses organizational forms and MSO activities, such as managed care contracting, billing, information systems, utilization management and review, the provision of supplies, medical office space, equipment, staff, and turnkey arrangements. In addition, it discusses the structuring of MSO fees and a number of organizational structures for MSOs and legal issues affecting them. PMID- 8191493 TI - Financing of integrated delivery systems. AB - This chapter addresses the financing of integrated delivery systems. It discusses the assessment of financing needs and taxable financing options, including standard commercial loans, lines of credit, commercial paper, and taxable bonds. The chapter also addresses tax-exempt financing, including tax-exempt bonds, and eligibility for tax-exempt financing. PMID- 8191494 TI - The antitrust risks of management services organizations, medical foundations, and integrated delivery systems. AB - This chapter focuses on the antitrust implications of forming a fully integrated delivery system. The danger lies in a challenge by the federal government or private parties, if the proposed system threatens the development of competing systems or excludes individuals or entities. By explaining the risks facing less integrated arrangements involving medical foundations and management services organizations, why forming an integrated system may resolve some of those risks, and the advantages and disadvantages of other options, this chapter also points out one of the primary benefits of forming an integrated system: reducing the antitrust risks. Finally, general suggestions are posed to minimize the antitrust risks when planning and developing any collaborative effort among providers. PMID- 8191495 TI - Tax exemption and integrated delivery systems. AB - This chapter discusses tax exemption of integrated delivery systems, including the requirements for exemption, the charitable purposes test, the private inurement and private benefit tests, and an application to integrated delivery systems. It also discusses the structure of the Friendly Hills and Facey Nonprofit Medical Foundations, including the analysis of the Internal Revenue Service. Finally, it discusses the process for obtaining tax exemption. PMID- 8191496 TI - Special Medicare reimbursement and fraud and abuse considerations for management services organizations, medical foundations, and integrated delivery systems. AB - This chapter discusses certain Medicare reimbursement and fraud and abuse considerations for management services organizations (MSOs), medical foundations, and integrated delivery systems. It stresses the necessity of a business plan, the sources of capitalization that might be used in creating an integrated delivery system, and their effect on Medicare reimbursement. It also discusses related party principles and considerations and the Medicare "incident to" regulations. Furthermore, it discusses the application of certain Medicare safe harbor regulations on MSOs' structures and services, and those of medical foundations and integrated delivery systems. PMID- 8191497 TI - Miscellaneous legal issues affecting integrated delivery systems, foundations, and management services organizations. AB - This chapter addresses some of those legal issues that uniquely affect the formation or operations of an integrated delivery system (IDS), a foundation, or a management services organization (MSO), but which are not discussed in any other chapters. This chapter gives special insight and guidance on issues such as licensing, credentialing and peer review, employee benefit plans, prohibitions against physician self-referrals, and the rules on disclosure of ownership and control. PMID- 8191498 TI - Mercy Medical Foundation of Sacramento: a case study. AB - This is a case study of Mercy Medical Foundation of Sacramento and its affiliation with Medical Clinic of Sacramento, Inc. It provides background on the development of the foundation, factors leading to the affiliation, evaluation of models, and analysis of how the organizational structure was developed. Finally, it discusses how the model is operating and the implications for the parent corporation. PMID- 8191499 TI - Case study: the integration of a medical foundation and an independent practice association. AB - This chapter is a case study of a nonprofit medical foundation and an independent practice association. It discusses the different cultures and statutory, governance, and other issues, including the development of the bylaws and managed care agreement. PMID- 8191500 TI - Recent progress in the eye irritation test. AB - The rabbit eye irritation test based on the Draize method is required for the hazard assessment of chemicals and products that may come into contact with the eye. Due to the potential for the suffering of animals and subjectivity of the test, many modifications of the method have been made that involved a reduction in the number of animals and a refinement of techniques. Additionally, there has been significant development of in vitro alternatives. This paper reviews recent advances in the in vivo test and in vitro alternatives, as well as regulatory requirements. While the refinement of in vivo protocols has resulted in a reduction in the number and discomfort on animals, the development of in vitro alternatives could lead to an eventual replacement of animal studies. In view of the inherent simplicity of many in vitro methods, some of which comprise cell cultures, further research into the relevance/mechanism of effects is required. Batteries of in vitro tests, when properly validated, may be considered as replacements for animal testing. PMID- 8191501 TI - Reproductive and neurobehavioral effects of amaranth administered to mice in drinking water. AB - The color additive amaranth was given in the drinking water at levels of 0 (control), 0.025, 0.075, and 0.225% from 5 weeks of age in F0 generation until F1 generation mice were weaned, with selected reproductive, developmental and behavioral parameters being measured. Amaranth had little adverse effect upon litter size, litter weight and sex ratio. Average body weight in both sexes of the F1 mice was significantly increased in the 0.025% group in both sexes. Survival index at postnatal day (PND) 21 was reduced in the 0.025% amaranth group. For the neurobehavioral parameters, surface righting at PND 4 in female offspring and olfactory orientation in both sexes were significantly affected by treatment. Several parameters of movement activity of male offspring at 3 weeks of age were affected in amaranth 0.075% group, but those of female offspring were similar in all groups. The dose levels of amaranth in this study produced a little adverse effect on behavioral development in mice. PMID- 8191502 TI - Promotion of peripheral axonopathies by certain esterase inhibitors. AB - Certain esterase inhibitors were found to exacerbate the clinical signs of polyneuropathy caused by various neurotoxic compounds and to delay the recovery from nerve crush. This phenomenon is referred to as promotion of axonopathies. The molecular target of promotion has not yet been identified. However, all known promoters are also inhibitors of neuropathy target esterase (NTE), the putative target of organophosphate neuropathy, but it has been shown that the target of promotion is unlikely to be NTE. Available data suggest that promoters might affect a target and a mechanism present in the nervous system that is not activated by axonal lesions. Promotion may be important to understand the physiological mechanism of nerve damage and repair. This finding also implies a changing perspective for the risk assessment of exposures to esterase inhibitors, some of which are used as pesticides and might be promoters. PMID- 8191503 TI - A neurotoxicity assessment of high flash aromatic naphtha. AB - Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide-boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9 carbon aromatic molecules (C9 Aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent also known as High Flash Aromatic Naphtha (HFAN). A program was initiated to assess the toxicological properties of HFAN since there may be human exposure, especially in the workplace. The current study was conducted to assess the potential for neurotoxicity in the rat. Adult male Sprague-Dawley rats of approximately 300 grams body weight, in groups of twenty, were exposed by inhalation to HFAN for 90 days at concentrations of 0, 100, 500, and 1500 ppm. During this period the animals were tested monthly for motor activity and in a functional observation battery. After three months of exposure, for 6 hours/day, 5 days/week, 10 animals/group/sex were sacrificed and selected nervous system tissue was examined histopathologically. No signs of neurotoxicity were seen in any of the evaluated parameters, nor was there evidence of pathologic changes in any of the examined tissues. PMID- 8191504 TI - The Agency for Toxic Substances and Disease Registry's role in development and application of biomarkers in public health practice. AB - An overview of the Agency for Toxic Substances and Disease Registry's (ATSDR) biomarker program is presented in the context of the paradigm for biomarkers developed by the National Research Council (NRC, 1987, 1991). The status and projected utility of four biomarker studies conducted by NRC and sponsored by ATSDR, the Environmental Protection Agency (EPA), and the National Institute of Environmental Health Sciences (NIEHS) are discussed. These studies include a review of relevant research on biomarkers for specific toxicologic end points, including reproductive toxicology, pulmonary toxicology, neurotoxicology, and immunotoxicology. Also, the scope of related research on exposure characterization being conducted by the ATSDR-sponsored research program at Rutgers University is reviewed. The potential impact of biomarkers on public health assessments and on the range of ATSDR programs is described. Specifically, the role of biomarkers in dose reconstruction, in ATSDR's health studies program, and in the emerging field of molecular epidemiology is reviewed. In addition, future directions and research needs are addressed. PMID- 8191505 TI - The comparative toxicity of operational Air Force hydraulic fluids. AB - The subchronic (26 day) oral toxicities of two AF hydraulic fluids (MIL-H-5606 [H5], MIL-H-83282 [H8]), a commercial phosphate ester (PE), and two candidate hydraulic fluids (low temperature version of MIL-H-83282 [LT] and chlorotrifluorethylene oligomers [polyCTFE]) were compared in male F-344 rats. Oral dosing was used in order to quickly compare these fluids to PolyCTFE, the only fluid at the time to have been tested in a 90-day inhalation study. Rats were initially dosed with 1.0 g/kg/day of each fluid. H8 increased alkaline phosphatase (ALKP) while LT produced an anemia and leukocytosis. Exposure to H5 fluid resulted in lymphocytopenia and persistent diuresis. Due to their greater toxicity, resulting in lethality in the first dosing study, only 0.5 g/kg/day of PE and PolyCTFE were administered in the second study. Exposure to PE (0.5 g/kg) resulted in an anemia and decreases in BW (day 10 until day 25), spleen/BW ratio, blood urea nitrogen (BUN), and creatinine (CREAT). PolyCREAT (0.5 g/kg) decreased BW (day 11 to the end of the study) and testicular weight. PolyCTFE (0.5 g/kg) increased relative spleen weights, various clinical chemistry parameters, and triggered a reversible diuresis. PolyCTFE (0.5 g/kg), PE (0.5 g/kg), and H5 produced an increase in absolute and relative liver weights compared to control livers. Peroxisomal beta oxidation, an indicator of peroxisomal proliferation, was significantly increased above control levels in the livers of all rats except the PE (0.5 g/kg) group, where the increase was not significant. Hydrocarbon nephropathy, indicated by increased levels of hyaline droplets in kidney tubules, was severe in H5, mild in H8, LT, and PolyCTFE (0.5 g/kg), and minimal in PE (0.5 g/kg). The MIL-H-83282 fluids (H8 and LT) were the least toxic hydraulic fluids. PolyCTFE and PE were the most toxic, with H5 intermediate. PMID- 8191506 TI - [The use of toothpaste with vitamin C in treating periodontitis]. AB - Toothpaste with vitamin A and a control paste without it were used in the treatment of periodontitis. The paste with vitamin A noticeably reduced gingival bleeding activity and proved to be effective in the treatment of young patients and of those with mild periodontitis. PMID- 8191507 TI - [The reactions of periodontitis patients to the administration of bacterial allergens]. AB - Analysis of the clinical picture of periodontitis and the results of allergologic tests with administration of hemolytic streptococcus and staphylococcus allergens indicated the formation in the patients of delayed type bacterial hypersensitivity which was weakly manifest and more characteristic of patients with medium-severe or grave periodontitis. Changes in the peripheral blood were also indicative of total body reaction to the local process in the periodontium; immune defense mechanisms were found strained and exhausted. PMID- 8191508 TI - [The malignant degeneration of lichen ruber planus of the oral mucosa]. PMID- 8191509 TI - [The immunological status of patients with vesicular eruptions on the oral mucosa]. AB - Immunologic examinations of 14 patients with vesicular form of lichen ruber and benign nonacantholytic pemphigus of the buccal mucosa alone, as well as of those with erythema exudativum multiforme demonstrated a normal (and even increased) response of immunity system to a chronic antigenic stimulus. The T system was found not involved, and a reduction of the share of B cells was revealed. The results are indicative of strained functioning of the immunity system paralleled by quantitative exhaustion of the B component. PMID- 8191510 TI - [The microbial flora and humoral protective factors in odontogenic inflammations in the maxillofacial area]. AB - Some features in the pathogenesis of various forms of an inflammatory process were demonstrated by immunologic and microbiologic methods in patients with odontogenic infections. A close relationship has been revealed between microflora of an inflammatory focus, immune response type, and inflammation course in the maxillofacial area. PMID- 8191511 TI - [The patient's own staphylococcal strains of nasal origin as potential causative agents of inflammatory processes in the maxillofacial area]. AB - Buccal mucosa was microbiologically examined in 1169 stomatologic patients, nasal mucosa (anterior segments) in 1035, and foci of involvement in 494 patients. High staphylococcal contamination of the nasal mucosa of stomatologic patients was found to be a stable parameter not depending on patients' age, sex, disease entity, or season. The intensity of oral contamination depends on a number of factors, such as age, sex, disease entity, and season, as well as the degree of nasal cavity contamination with staphylococci. These factors' effects appear to be realized via salivary antibacterial properties. Phage typing results and antibioticograms of the defected staphylococci indicate that the majority of these microorganisms contaminating the oral cavity originate from the nasal cavity. A conclusion is made about advisability of nasal cavity treatment with antistaphylococcal agents to prevent pyoinflammatory complications after surgical interventions, as well as in patients with maxillofacial injuries. PMID- 8191512 TI - [The use of hemosorption in treating severe forms of stomatitis]. AB - Analyzes the results of hemoperfusion used in multiple-modality treatment of 33 patients with grave forms of stomatitis. Enumerates indications for such therapy, methods of homeostasis control, and for assessment of hemoperfusion efficacy. Reduction of treatment periods from 23.4 days in controls to 19.0 days in experimental group indicate a high efficacy of hemoperfusion in the treatment of grave stomatitis. PMID- 8191513 TI - [The comparative efficacy of different physiotherapy combinations in treating mandibular fractures]. AB - The authors compare the efficacy of IR laser, a combination of magnetic laser radiation and UHF electric field followed dy calcium chloride electrophoresis on the course of mandibular fracture healing. With this purpose 114 patients with uni- and bilateral mandibular fractures were examined and administered a course of preventive treatment. Analysis of the clinical data, subjective sensations of the injured subjects, and data of functional diagnostic methods (rheography, polarography, echo-osteometry) brought the authors to a conclusion on a positive effect ot IR laser and, more so, of magnetic laser therapy on the recovery of regional hemodynamics and oxygen homeostasis of tissues at the site of injury, this being conducive to reduction of pyoinflammatory complications and a sooner rehabilitation of the patients. These results recommend IR laser combined with magnetic field exposure for multiple-modality treatment of patients with mandibular fractures, particularly for those with marked dislocation of bone fragments and regional blood flow disturbances. PMID- 8191514 TI - [The bilateral autonomy of enzyme secretion by human salivary glands]. AB - Saliva secreted by right and left parotid glands was collected using Leshley Krasnogosky's capsules. Salivary secretion and aminolytic activity were found to be higher on the chewing side than on the contralateral. Bilateral differences in salivary gland secretion of alkaline and acid phosphatases and pepsinogen were less expressed. Salivary secretion in right-handed and left-handed subjects and in patients with hemiplegias after brain stroke was studied by citric acid stimulation. Bilateral asymmetry of enzymic secretion was revealed, particularly marked in the patients: not only the volume of salivary production and enzyme debit, but salivary enzymic activity on the side of motor paralysis were lower than on intact side. Bilateral functional asymmetry of secretion was more manifest for amylase than for other enzymes whose origin is largely influenced by recretion process. PMID- 8191516 TI - [The nature of the distribution of functional stresses in the maxilla]. AB - The patterns of strain and deformation distribution in the maxilla were examined during normal exercise concentrated at the median incisors on a skeletonized jaw. Electrotensometry and mathematical calculations were used in the study. Causes of extending and compressing tensions and deformations in the mandible were detected, the knowledge of these causes will be conducive to rational fixation and prostheses on the maxilla. PMID- 8191515 TI - [An x-ray method for estimating the size of the oral cavity]. AB - Presents a modified method for x-ray assessment of oral cavity size making use of long-distance roentgenography in the lateral projection and demonstrates the efficacy of this method in planning reconstructive surgery on the bones. PMID- 8191517 TI - [Experience in using computed tomography in the diagnosis of diseases of the maxillofacial area]. AB - Thirty patients aged 19 to 70 suffering from various diseases and injuries of maxillofacial organs and tissues (chronic odontogenic osteomyelitis, sinusitis, malignant and benign neoformations of the jaws and perimaxillary soft tissues, injuries to facial skull) were examined using computer-aided tomography. The method is described in detail, its potentialities in the diagnosis of the said diseases and injuries are demonstrated. PMID- 8191518 TI - [A clinical evaluation of the use of dentures with a Simet glass-ceramic coating]. AB - Positive follow-up results achieved in patients with metal-glass ceramic dentures coated with Simet permit the authors to recommend glass ceramic Simet for wide clinical introduction. In reconstructive dental prosthetics with metal glass ceramic and cermet materials the dentures should be modelled in the articulator. Preventive examinations are recommended once in half a year. PMID- 8191519 TI - [The preparation of the maxillodental system before using using metal-ceramic dentures]. AB - Orthodontic treatment using cermet dentures was carried out in 496 patients aged 26 to 60. Therapeutic surgical and orthodontic treatment of the maxillodental system was carried out before denture fixation. Late results in periods from 1 to 5 years were followed up in 396 patients. No complications were observed in 384 (96.9%). Only 12 patients developed complications: porcelain fracture in 4, periodontal inflammations in 5, and a partial relapse of occlusion reduction and distal dislocation of the mandible in 3. PMID- 8191520 TI - [The results of using Unifas cement for denture fixation]. AB - Unifas cement was used for fixation of cermet dentures in 104 patients. Clinical follow-up of 3 months to 3 years duration demonstrated sufficiently high adhesive characteristics, resistance to oral fluid and mechanic loading effects of this cement, which is recommended for wide clinical practice. PMID- 8191521 TI - [Thymalin in the treatment of herpetic stomatitis in children]. AB - Thymalin, a polypeptide drug obtained by extraction from cattle thymus, was used in therapy of 44 children with acute and relapsing herpetic stomatitis. Laboratory studies included direct analysis of fluorescent antibodies in buccal mucosa epithelium to verify the clinical diagnosis and enzyme immunoassay of specific antigen in salivary samples before and after therapy. Enzyme immunoassay was also used to assay antibodies to herpes simplex virus in the blood serum over the course of treatment. Immunity status over the course of treatment was assessed by indirect immunofluorescence with monoclonal antibodies used to study lymphocyte subpopulations CD4+ inductor-helpers, CD8+ natural killers, and CD4+/CD8+ ratio. Thumalin therapy was not conducive to a rapid abatement of acute symptoms in stomatitis; but such therapy is justified, for in helps attain a stable antirelapse effect in children at a high risk of developing stomatitis recurrences. PMID- 8191522 TI - [The rehabilitation of patients with congenital cleft palate]. AB - A complex of rehabilitation measures carried out in children with cleft palate before and after surgery includes ultrasonic therapy and electrostimulation before the operation. Infrared laser and alternating magnetic field are used after surgery in the immediate period. After sutures are removed logopaedic training and orthodontic treatment are parallelled by electrostimulation. Such a complex helps prevent postoperative complications and accelerates speech rehabilitation of children. PMID- 8191523 TI - [The personality of the dentist as a factor in the therapeutic impact on patients]. AB - Relationships between the dentist and his (her) patient depend on the psychologic status of both. The dentist's temper and emotional requirements, as well as, though to a lesser degree, patient's temper and his/her mental abnormalities are sources of potential complications in these relationships. The personality of a dentist is virtually never regarded in literature as a factor of therapeutic action on the patients over the course of fitting them with dentures. The present paper deals with the deontologic situation dentist-patient. PMID- 8191524 TI - [Megastenon: its clinical manifestations and treatment with intra- and extraductal laser therapy]. AB - The authors present the data on examinations and follow-up as well as result of combined treatment of 13 patients with abnormally enlarged greater salivary ducts. Clinical manifestations of this rare disease are considered. He-Ne laser therapy in low-energy mode resulted in improvement in 12 patients with complete morphological recovery of the salivary glands in 3 of them. PMID- 8191525 TI - [The sequential use of remineralization solutions and sodium fluoride recommended for the prevention and treatment of dental caries and for treatment at the white spot stage]. PMID- 8191526 TI - [Damage to the floor of the maxillary sinus and the therapeutic approach]. AB - In 1974-1991 the authors followed up 402 and 220 patients with odontogenic and rhinogenic maxillary sinusitis, respectively. It is confirmed that the leading cause of odontogenic sinusitis is periapical inflammation, while perforation of the sinus base in removal of the tooth is the sequela. In dissection of the sinus base free of sinusitis suturing of the hole or its closure with mucoperiosteal graft may warrant the clot persistence in the hole. Injuries of the sinus base are divided into chance and suspected, recognizable and missed, complicated and noncomplicated, perforation with complete and incomplete tooth removal. Therapeutic policy should be designed on the individual basis depending on the odontogenic cause. PMID- 8191527 TI - [A method for the plastic repair of congenital clefts of the lower lip]. PMID- 8191528 TI - [The combined treatment of mandibular fractures]. AB - A total of 164 patients with mandibular fractures were followed up. Consolidation was assessed on the basis of clinical, X-ray, echo-osteometric, and electromyographic studies. In patients whose multimodality therapy involved ultrasound, fragment adhesions occurred on an average of 27.5 +/- 1.9 and 31.0 +/ 2.1 days later in uni- and bilateral fractures, respectively. The patients' working ability restored on days 32.0 +/- 1.3 and 34.0 +/- 1.1, while in a group of patients treated by routine methods, these periods became longer by 3.5-6.2 and 2.0-6.0 days, respectively. The duration of rehabilitation approximately doubled. Ultrasound is recommended for wide use in diagnosis and clinical practice to stimulate reparative processes in mandibular fractures. PMID- 8191529 TI - [The use of special scissors in cutting the frenulum of the upper lip]. PMID- 8191530 TI - [An analysis of tooth preservation after the treatment of caries and its complications]. PMID- 8191531 TI - [The theoretical and experimental-clinical validation of the specific prevention of dental caries with preparations made from Streptococcus mutans]. PMID- 8191532 TI - [Electrogenesis in the jaw bones and teeth and its possible use in practical dentistry (a review of the literature)]. PMID- 8191533 TI - [The use of intraosseous anesthesia in dental practice]. PMID- 8191534 TI - [Current problems in improving the postgraduate training of public health management personnel]. AB - Improvement of advanced training of heads of dentistry institutions is one of the pressing problems in the days of transferring public health service into a new economic system. Curricula, forms and methods of training should be revised to become more practically directed. Purposeful training should be carried out on an agreement basis. PMID- 8191535 TI - [The chemical element content of mixed unstimulated saliva in periodontal diseases]. AB - The levels of 21 chemical elements (N, Na, Mg, P, Cl, K, Ca, Sr, Cr, Mn, Fe, Co, Zn, Se, Br, Rb, Sc, Ag, Sb, Hg) were measured in mixed unstimulated saliva of 50 patients with periodontal diseases (29 women and 21 men) aged 20 to 49 without concomitant diseases, five of these with gingivitis and the rest with generalized periodontitis of medium severity (27 cases) and grave (n = 18). A control group consisted of 52 healthy subjects with intact periodontium and teeth. A complex of instrumental methods has been developed and used in this study including neutron activation analysis (NAA) in two modifications and roentgen-fluorescent analysis. Changes in salivary levels of chemical elements were detected in the patients, these changes augmenting with severity of periodontal tissue involvement. In grave condition the concentrations of the major electrolytes were increased by 2.3 to 6.6 times on an average, of nitrogen twofold, of scandium, manganese, and chromium by 6.8-8.8 times, and of iron, cobalt, copper, selenium, bromine, silver, and mercury by 1.6-1.9 times; zinc level in mixed salivary protein reduced as the disease augmented in severity and in a grave form was only 62% of its normal content (p < 0.01). Salivary oversaturation with ions including Ca2+ which are conductive to salivary glycoprotein sedimentation and eventually to formation of a nutrient medium for pathogenic bacteria and zinc deficit indirectly indicating a reduced level of immunity status of the body are additional factors responsible for increased rate of dental deposit formation in periodontal diseases. PMID- 8191536 TI - Expression of 11 beta-OHSD along the nephron of mammals and humans. AB - The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) plays a major role in the protection of the mineralocorticoid receptor (MR). This cellular mechanism of aldosterone selectivity relies on the coexpression of MR and 11 beta-OHSD in the same cells. Localization of renal 11 beta-OHSD along the nephron is reviewed; comparison of data contained in different species is made; and original data is presented to show that the catalytic activity of the enzyme in tubules from human kidney is the highest in the mineralocorticoid-sensitive distal nephron. PMID- 8191537 TI - 11 beta-Hydroxysteroid dehydrogenase in renal collecting duct cells. AB - The purpose of this paper it to briefly review recent work from our laboratory dealing with the form of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) present in renal aldosterone target cells. It is well established that aldosterone is the physiological mineralocorticoid hormone. The observation that mineralocorticoid receptors have equal affinity for aldosterone and endogenous glucocorticoids, coupled with the fact that circulating levels of glucocorticoids are much higher than those of aldosterone, raises the question of how aldosterone can fulfill its function. To explain this paradox, it was hypothesized that in mineralocorticoid target tissues 11 beta-OHSD rapidly inactivates glucocorticoids (but not aldosterone), thereby decreasing intracellular glucocorticoid levels, so that aldosterone can exert specific regulation via the mineralocorticoid receptor. However, the only form of this enzyme which has been cloned thus far might not be the enzyme which is able to confer aldosterone selectivity on the mineralocorticoid receptor. On the other hand, a new form of 11 beta-OHSD (11 beta-OHSD/CD) that we have discovered in renal collecting duct cells possesses all the properties necessary for protecting the mineralocorticoid receptor: very high affinity for endogenous glucocorticoids, high abundance in target cells, and irreversible dehydrogenase activity. Our hypothesis is that 11 beta-OHSD/CD is the enzyme that ensures aldosterone selectivity in mineralocorticoid target cells, and that is the product of a gene different from the one previously cloned. PMID- 8191538 TI - Genetic analysis of 11 beta-hydroxysteroid dehydrogenase. AB - 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) catalyzes the interconversion of cortisol and cortisone. This activity is postulated to protect the Type I (mineralocorticoid) receptor from excessive concentrations of cortisol, allowing aldosterone to function as a mineralocorticoid. An enzyme with 11 beta-OHSD activity was isolated from rat liver and the corresponding rat and human cDNA and genomic clones isolated. This enzyme is a member of the short-chain dehydrogenase family. Using site-directed mutagenesis, it was demonstrated that the amino terminus and two highly conserved residues, Tyr-179 and Lys-183, are required for enzymatic function. Examination of patients with apparent mineralocorticoid excess, a syndrome of juvenile hypertension thought to represent 11 beta-OHSD deficiency, did not reveal any mutations in the HSD11 gene. This disorder may involve an additional enzyme with 11 beta-OHSD activity or possibly another cortisol metabolizing enzyme. PMID- 8191539 TI - Isozymes of 11 beta-hydroxysteroid dehydrogenase: which enzyme endows mineralocorticoid specificity? AB - Intracellular enzymes which interconvert circulating hormones between active and inactive forms aid in regulating the biological activity of the ligand in a cell specific manner. This is particularly important in mineralocorticoid target tissues where glucocorticoids and mineralocorticoids have equivalent affinity for the mineralocorticoid receptor. Inactivation of glucocorticoids at the 11 hydroxyl position by the action of 11 beta-hydroxysteroid dehydrogenase (11 beta OHSD) permits the occupation of the mineralocorticoid receptor by aldosterone in the presence of much higher levels of circulating cortisol. The suppression of dehydrogenase activity allows glucocorticoids to activate the mineralocorticoid receptor, leading to classical mineralocorticoid type effects such as sodium retention and potassium excretion. A number of 11 beta-OHSDs are currently candidate protectors of the mineralocorticoid receptor. This review examines the attributes of these 11 beta-hydroxysteroid dehydrogenase isozymes and suggests reasons why a high affinity, NAD-dependent enzyme appears to be the most likely candidate to endow specificity on the mineralocorticoid receptor. PMID- 8191540 TI - Analysis and pharmacokinetics of glycyrrhizic acid and glycyrrhetinic acid in humans and experimental animals. AB - Glycyrrhizic acid (GZA) and glycyrrhetinic acid (GRA) can be determined rapidly and precisely by high-performance liquid chromatography (HPLC) in biological fluids and tissues from experimental animals and humans. From plasma and tissues, GZA and GRA are extracted by organic solvents and the extracts can directly be used for HPLC. From bile or urine, extraction and determination of GZA and GRA are more difficult due to interfering endogenous compounds and conjugation of GRA with glucuronides or sulfates. Extraction of GZA and GRA from urine or bile can be performed by ion-pairing followed by extraction with organic solvents or by solid phase extraction. GRA conjugates can be determined by chromatographic separation or by pretreatment with beta-glucuronidase. The pharmacokinetics of GRA and GZA can be described by a biphasic elimination from the central compartment with a dose-dependent second elimination phase. Depending on the dose, the second elimination phase in humans has a half-life of 3.5 hours for GZA and between 10-30 hours for GRA. The major part of both GRA or GZA is eliminated by the bile. While GZA can be eliminated unmetabolized and undergoes enterohepatic cycling, GRA is conjugated to GRA glucuronide or sulfate prior to biliary excretion. Orally administered GZA is almost completely hydrolyzed by intestinal bacteria and reaches the systemic circulation as GRA. PMID- 8191541 TI - Licorice ingestion and blood pressure regulating hormones. AB - Nearly half a century ago Revers reported that administration of a paste prepared from succus liquiritiae, a dried watery extract of the roots of Glycyrrhiza glabra, resulted in a reduction in abdominal symptoms as well as radiographic evidence of healing in patients suffering from gastric ulcer. Subsequent studies demonstrated that this preparation could prevent the formation of gastric ulcers in experimental animals and confirmed the salutary effects in patients, but found that approximately 20% of patients so treated developed facial and dependent edema, often accompanied by headache, shortness of breath, stiffness, and pain in the upper abdomen. Although these symptoms suggested an allergic reaction, they were not accompanied by eosinophilia or relieved by antihistamines. These untoward effects usually subsided with a reduction of dose, although in some patients treatment had to be discontinued entirely. Given this profile of side effects, enthusiasm for licorice as a remedy for peptic ulcer disease soon faded. However, the popularity of licorice flavoring in candy and in other products such as chewing tobacco persists to this day, as do the problems in electrolyte and blood pressure homeostasis that can occasionally occur in individuals ingesting large quantities of licorice-containing products. Although the pattern of the renal response suggested that the active ingredients in licorice were acting directly on the mineralocorticoid receptors in the kidney, an even more fascinating explanation for the toxic effects of licorice has emerged in the past decade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191542 TI - Endogenous inhibitors of 11 beta-OHSD: existence and possible significance. AB - Inhibition of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) by licorice derived compounds and in cases of idiopathic impairment of this enzyme is known to result in hypermineralocorticoid syndromes, reflecting corticosteroid receptor activation by excess intracellular glucocorticoids. In this paper we address the question of whether or not endogenous inhibitors of 11 beta-OHSD exist that might cause pathological glucocorticoid metabolism. Using microsomal preparations we have demonstrated that bile acids are potent inhibitors of rat renal and human hepatic 11 beta-OHSD, with lithocholic acid exerting the strongest effect. The human renal enzyme is affected to a lesser extent. Serum of patients with cholestatic liver cirrhosis also inhibited 11 beta-OHSD activity, in parallel with total bile acid concentration. Cholesterol and its precursor lanosterol inhibited the enzymatic activity in microsomes from rat and human kidney cortex and human liver. We conclude that bile acids could contribute to the abnormalities of cortisol metabolism observed in cholestatic liver cirrhosis. PMID- 8191543 TI - Licorice and enzymes other than 11 beta-hydroxysteroid dehydrogenase: an evolutionary perspective. AB - Licorice has long been known to promote the healing of ulcers. In the 1950s, studies with licorice-derived compounds revealed that the anti-ulcer effects of licorice are due to inhibition of 15-hydroxyprostaglandin dehydrogenase and delta 13-prostaglandin reductase. 15-Hydroxyprostaglandin dehydrogenase converts prostaglandins E2 and F2 alpha to 15-ketoprostaglandins, which are inactive. delta 13-Prostaglandin reductase metabolizes the inactive delta 13-prostaglandin to 13,14-dihydro,15-ketoprostaglandin, which is further metabolized and excreted in urine. Thus, licorice-derived compounds have the effect of raising the local concentration of prostaglandins that promote mucous secretion and cell proliferation in the stomach, leading to healing of ulcers. 11 beta Hydroxysteroid dehydrogenase, which also is inhibited by licorice-derived compounds, shares a common ancestor with 15-hydroxyprostaglandin dehydrogenase. Both enzymes are homologous to Streptomyces hydrogenans 3 alpha,20 beta hydroxysteroid dehydrogenase, which also is inhibited by licorice. Thus, licorice inhibits enzymes that diverged at least 2 billion years ago from a common ancestor. Other oxidoreductases in bacteria, plants, and animals that are inhibited by licorice-derived compounds are likely to be discovered in the future. PMID- 8191544 TI - Other physiological considerations of protective mechanisms of mineralocorticoid action. AB - Mineralocorticoid receptors (MR) are protected from the effects of endogenous glucocorticoids (GC) in mineralocorticoid (MC) target tissues such as the kidney and the parotid gland. This protection is thought to be provided by 11 beta hydroxysteroid dehydrogenase (11 beta-OHSD). 11 beta-OHSD metabolizes cortisol (in humans) and corticosterone (B) (in the rat) to cortisone and 11-dehydro-B, their respective inactive dehydro products. We have previously shown that the antinatriuretic actions of the MC deoxycorticosterone (DOC) are amplified in carbenoxolone (CBX) treated adrenalectomized (ADX) rats. CBX is believed to inhibit 11 beta-OHSD activity; DOC, however, is not a substrate for this enzyme. We now report on 11-desoxycortisol (11-desoxy-F) and 2 alpha-methylcortisone, substances which possess no intrinsic antinatriuretic activity, are not metabolized by 11 beta-OHSD and yet cause Na+ retention in CBX-treated ADX rats. Given that none of the above steroids are substrates for 11 beta-OHSD it is unlikely that the inhibition of this enzyme is involved in the unmasking of the Na+ retention observed when these substances are given to CBX-treated animals. These results provide further evidence for an additional protective mechanism, that protects MR from the inappropriate binding of excessive amounts of endogenous MCs. PMID- 8191545 TI - Active, interactive, and inactive steroid receptor mutants. AB - In transient co-transfection assays, there is extensive cross-interaction between glucocorticoid receptor (GR) domains. For example, mutation of the conserved Ile residue at position 484 (rat GR map) to cysteine allows a net separation of transactivation and DNA binding. We also observed that the ligand binding domain plays a key role in cooperative transactivation. Furthermore, some carboxy located mutations markedly alter the response of GR to agonists and antagonists. Finally, different reading frames of the CAG repeat that normally produces an amino-located poly-Gln repeat profoundly affect GR transactivation without altering DNA or ligand binding. This trans-dominant negative phenotype, seen when the CAG repeat yields a poly-Ala stretch, may turn out to be an excellent tool for functional analysis of GR in transgenic organisms. PMID- 8191546 TI - A mechanistic basis for distinct mineralocorticoid and glucocorticoid receptor transcriptional specificities. AB - The mineralocorticoid and glucocorticoid receptors (MR and GR, respectively) are closely related members of the nuclear receptor superfamily. Despite marked functional similarities and a high degree of sequence conservation between MR and GR, the mineralocorticoid and glucocorticoid hormones elicit markedly different physiological effects, even in cells expressing both receptors. Hormone specificity is, in part, determined by the actions of 11 beta-hydroxysteroid dehydrogenase. However, other mechanisms must obtain in cells that express both receptors and respond differentially to the two classes of hormone. Indeed, MR and GR, while functionally redundant in some contexts, in others display distinct transcriptional specificities. In particular, in the presence of members of the AP1 family of regulatory factors, cJun and cFos, a composite response element, plfG, is GR-specific. Transcription from a plfG-linked gene is stimulated by GR in the presence of cJun and repressed by GR in the presence of cJun and cFos. MR neither stimulates nor represses transcription in the same contexts, thus indicating that receptor transcriptional specificities can be distinguished by differential interactions with nonreceptor factors at a composite response element. The implications of these findings for mineralocorticoid and glucocorticoid hormone specificity in various tissues are discussed. PMID- 8191547 TI - Novel aldosterone receptors: specificity-conferring mechanism at the level of the cell membrane. AB - Functional studies in extra-renal, nonepithelial cells such as smooth muscle cells and more recently circulating human lymphocytes have provided increasing evidence that aldosterone produces not only classical genomic effects, but also rapid non-genomic effects on transmembrane electrolyte movements. These involve activation of the sodium/proton-exchanger of the cell membrane at very low, physiological concentrations of aldosterone with an acute onset within 1-2 minutes. A second messenger cascade involved is the inositol-1,4,5 trisphosphate/calcium pathway which responds over the same rapid time course. Such changes clearly cannot be explained by genomic mechanisms, which are responsible for later effects than the membrane-related rapid responses. In addition to its rapid time course the unique characteristics of this new pathway for steroid action include a 10000-fold selectivity for aldosterone over cortisol and the ineffectiveness of spironolactones, classical mineralocorticoid antagonists, as antagonists of the response. Subsequently binding sites have been demonstrated in the plasma membrane of human lymphocytes which show pharmacological (aldosterone specificity) and kinetic (high turnover) properties identical with those of the rapid aldosterone effects in the same cells. SDS-PAGE analysis of the receptor protein has shown a molecular weight of approximately 50 kD. The present paper reviews the data supporting a new, two-step model for non genomic and genomic aldosterone effects. It also suggests a novel specificity conferring mechanism for mineralocorticoid action at the membrane level. PMID- 8191548 TI - Enzymes and receptors: challenges and future directions. AB - In many ways, the present paper will cover much of the same ground as those that precede it. As its title suggests, it is an overview--in part to highlight various aspects of the areas which have been discussed, and in part to put a personal view of where the most fruitful avenues for exploration over the next two years lie. It is very clearly not a comprehensive summary of the topic; given the delightful unpredictability of biological advance, there is every likelihood such predictions may prove substantially wrong. On the other hand, nothing ventured, nothing won; and so with this caveat, there follows one man's reckoning of the directions for the immediate future. PMID- 8191549 TI - Apparent mineralocorticoid excess: a personal history. PMID- 8191550 TI - Comparative aspects of 11 beta-hydroxysteroid dehydrogenase. Testicular 11 beta hydroxysteroid dehydrogenase: development of a model for the mediation of Leydig cell function by corticosteroids. AB - It has been shown that stress or disease-induced increases in plasma corticosterone result in diminished testosterone secretion from the testes. This article reviews investigations from our laboratories that explore the role of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) in this process. It is proposed that the level of 11 beta-OHSD in Leydig cells dictates the level of intracellular glucocorticoid available to the glucocorticoid receptor and thus the potency of corticosteroid as an inhibitor of testosterone secretion. Stressed and unstressed rats were housed under simulated natural conditions in a Visible Burrow System. Stressed animals showed elevated plasma corticosteroid, lowered plasma testosterone, and diminished testicular 11 beta-OHSD, Immunocytochemical analysis showed that only Leydig cells of the rat testis contain 11 beta-OHSD and glucocorticoid receptors. Half-maximal inhibition of testosterone by Leydig cells required 1.5 nM dexamethasone or 0.4 microM corticosterone. Glycyrrhetinic acid, an inhibitor of 11 beta-OHSD, increased the potency of corticosterone, but did not affect dexamethasone based inhibition. The glucocorticoid receptor blocker, RU 486, prevented inhibition by both corticosterone and dexamethasone. Other classes of steroid were not inhibitors of testosterone biosynthesis. Thus, 11 beta-OHSD oxidizes corticosterone to the inactive metabolite 11 dehydrocorticosterone, relieving steroid-dependent inhibition of Leydig cell function. Lowered enzyme activity increases glucocorticoid dependent inhibition of testosterone production. We conclude that the evidence supports a role of 11 beta-OHSD in testosterone secretion by the testes. PMID- 8191551 TI - Pharmacology of 11 beta-hydroxysteroid dehydrogenase. AB - In clinical practice synthetic glucocorticoids are mainly used as therapy for inflammatory disorders and in suppressing immunological responses to transplanted allografts. The presence of an 11 beta-hydroxyl (11 beta-OH) group is mandatory for the antiinflammatory effects of glucocorticosteroids. The interconversion of the 11 beta-OH into the corresponding 11-keto group and vice versa by 11 beta-OH steroid dehydrogenase might thus play a pivotal role for the efficacy of these steroids. Estimates of the apparent capacity to interconvert these steroids have been derived from plasma and tissue concentration measurements. Such estimates reveal that the interconversion process is concentration dependent and tissue specific. It remains to be established whether modulating that process might allow the immunosuppressive effect to be targeted within certain organs, thereby increasing the ratio between therapeutic and side effects of glucocorticoid administration. PMID- 8191552 TI - Apparent mineralocorticoid excess type II. AB - The syndrome of apparent mineralocorticoid excess (AME) is currently understood to reflect impaired peripheral metabolism of cortisol, which is then able to activate the non-selective mineralocorticoid (MC) receptor. The failure of glucocorticoid inactivation at the MC target tissue level in AME involves abnormal activity of 11 beta-hydroxysteroid dehydrogenase, with impaired conversion of cortisol to cortisone, and also of 5 beta-reductase. We have discovered a new form of AME (Type II) in four patients with the same clinical picture of hypertension, hypokalemia, and suppressed renin-angiotensin aldosterone system, but in whom this conversion seems either to be normal (since cortisol to cortisone metabolite ratio is normal) or to be impaired in both directions, leaving the ratio unchanged. Both types are characterized by a profound decrease in cortisol turnover quotient and Ring A reduction constant. Short-term dexamethasone treatment is effective in correcting the MC-derived abnormalities, while in the long term the addition of other antihypertensive drugs may be required to control the severity of hypertension. PMID- 8191553 TI - Organ-specific actions of 11 beta-hydroxysteroid dehydrogenase in humans: implications for the pathophysiology of hypertension. AB - Elucidation of a role for 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) in modulating ligand access to renal mineralocorticoid receptors, together with identification of expression of the enzyme in most mammalian tissues, has raised the possibility (i) that glucocorticoid metabolism might influence corticosteroid receptor activation in other sites which are relevant to blood pressure control (e.g., vascular smooth muscle), and (ii) that abnormal 11 beta-OHSD expression might play a pathogenic role in common forms of hypertension (e.g., essential hypertension and the syndrome of ectopic ACTH secretion). This article reviews data from human experiments which suggest that 11 beta-OHSD has tissue-specific actions which can increase or decrease sensitivity of both mineralocorticoid and glucocorticoid receptors to cortisol, and that assessment of cortisol sensitivity may prove equally important as assessment of cortisol secretion rates in hypertensive patients. PMID- 8191554 TI - 11 beta-Hydroxysteroid dehydrogenase activity and corticosteroid hormone action. AB - In normal physiology 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) protects the mineralocorticoid receptor (MR) from glucocorticoid excess. In the rat, however, 11 beta-OHSD mRNA and activity is widespread, suggesting that it may also play a role in regulating ligand access to the glucocorticoid receptor (GR). We have studied the role of the 11 beta-OHSD in modulating corticosteroid hormone action in rat pituitary GH3 cells (glucocorticoids inhibit prolactin gene transcription) and renal epithelial NRK-52E cells (mineralocorticoids increase Na K ATPase subunit gene expression) in culture. Both cell lines express high levels of 11 beta-OHSD activity, and Northern/Western blot analyses using a rat cDNA probe and antisera raised against rat liver 11 beta-OHSD reveal a single 1.4 Kb mRNA encoding an enzyme of molecular size 34 kDa. In GH3 cells, prolactin gene transcription was unaffected by corticosterone (B) in doses of 10(-8) to 10(-6) M. When 11 beta-OHSD activity was inhibited with the licorice derivative, glycyrrhetinic acid (GE); however, 10(-6) M B inhibited prolactin (PRL) mRNA levels to the same degree as an equimolar concentration of the GR agonist RU 28362. This effect was blocked by co-incubation with the GR antagonist RU 38486. In NRK-52E cells, co-incubation with B and GE resulted in a marked increase in alpha 1/beta 1 Na-K ATPase subunit mRNA levels when compared with GE and/or B alone and this effect could be blocked by administration of the MR antagonist RU 26752.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191555 TI - The enigma of pseudohypoaldosteronism. AB - The syndrome of primary pseudohypoaldosteronism (PHA) is a hereditary disease characterized by increased aldosterone secretion associated with clinical signs of hypoaldosteronism. These include salt wasting and failure to thrive in the newborn, high urinary sodium, hyponatremia, hyperkalemia, and metabolic acidosis. Plasma renin activity is usually elevated in association with aldosterone. The clinical manifestation of the disease is variable, including severely affected patients who may die in infancy and patients who are asymptomatic. The disease seems to result from a cellular resistance to mineralocorticoid action, which could be either generalized, or restricted to the kidney. The condition is inherited as an autosomal dominant or an autosomal recessive trait; however, sporadic cases have been described. In this paper we report a 20-year follow-up study of a French family affected by PHA and we discuss the pathogenesis of the disease. PMID- 8191556 TI - Changing patterns of blood use. PMID- 8191557 TI - Polyethylene glycol versus low-ionic-strength solution in pretransfusion testing: a blinded comparison study. AB - BACKGROUND: Polyethylene glycol (PEG) has been shown to potentiate antigen antibody reactions. STUDY DESIGN AND METHODS: To investigate the utility of PEG in pretransfusion testing, a blinded comparison study of PEG and a low-ionic strength additive solution (LISS) was conducted. A total of 500 patient samples were tested in parallel with reagent antibody-detection cells using blind-coded PEG and LISS potentiators. RESULTS: In 34 (34%) of 100 samples with known antibodies in the Rh, Kell, Duffy, Kidd, and MNS systems, PEG antiglobulin reactions were stronger (total score, 382) than LISS antiglobulin reactions (total score, 216), and in 66 cases (66%), they were equal to those of LISS. Of 400 samples without detectable antibodies, 384 were negative with PEG and LISS, and 16 were positive in PEG tests and negative in LISS. Seven of the 16 were clinically important antibodies (D, 1; E, 3; Fya, 1; Jka; 1; Jkb, 1), and four were clinically benign antibodies (Le(a), 2; McCc, 1; Sda, 1). Five of the 16 demonstrated inconclusive PEG reactions, for a false-positive rate of 5 in 400 (1.3%). Of the 500 samples, none was negative in PEG tests and positive in LISS (0% false-negative rate). CONCLUSION: Although PEG demonstrates a relatively high false-positive rate, PEG is more sensitive than LISS in detecting clinically significant antibodies. PMID- 8191558 TI - Multiple unconfirmed-reactive screening tests for viral antibodies among blood donors. AB - BACKGROUND: In December 1991, the United States Food and Drug Administration received reports of blood donations with unconfirmed reactivity on screening tests for antibodies to human immunodeficiency virus, human T-lymphotropic virus type I, and hepatitis C virus (HCV). Of 91 donors with these test results, 57 (63%) reported a recent influenza vaccination. STUDY DESIGN AND METHODS: To determine the extent of unconfirmed reactivity, the time at which it began, and its association or nonassociation with specific manufacturers' tests, a nationwide survey of blood centers was conducted. A case-donation was defined as a blood donation that was repeatedly reactive, but not confirmed positive, on at least two of the three tests from May 1990 through December 1991. RESULTS: Among 14 million donations screened by 110 centers, 582 case-donations were identified. An increase in case-donations was evident in the fall of 1990 (2.8/100,000 donations). In 1991, rates increased from 0.9 per 100,000 donations in the first quarter to 1.3, 3.2, and 19.7 in subsequent quarters. A significantly higher rate of case-donations was observed among donations tested with one of the two available anti-HCV screening tests (8.0 vs. 1.2/100,000 donations; risk ratio = 6.8; 95% CI = 5.4-8.5). CONCLUSION: Although unconfirmed reactivity on multiple screening tests appeared to be seasonal, its documentation prior to the availability of influenza vaccine in 1991 and higher rates among donations tested with one manufacturer's anti-HCV test indicated that test-specific factors were also involved. PMID- 8191559 TI - Detection of human immunodeficiency virus type 1 p24 antigen and plasma RNA: relevance to indeterminate serologic tests. AB - BACKGROUND: Most enzyme immunoassay-reactive specimens producing indeterminate Western blot results belong to individuals who are not infected with human immunodeficiency virus type 1 (HIV-1). However, a small percentage may correspond to early seroconversion or advanced disease, at which stage partial reactivity on Western blot may be observed. STUDY DESIGN AND METHODS: To determine the utility of HIV-1 p24 antigen and cell-free RNA detection for the resolution of Western blot-indeterminate serologic results, several types of enzyme immunoassay positive, sero-indeterminate specimens were analyzed. Samples were obtained from infected individuals at the time of seroconversion (n = 20), from patients with AIDS (n = 2), as specimens from clinical samples obtained for diagnostic testing (n = 57), from blood donors producing persistent indeterminate results (n = 47), and from random blood donors (n = 72). RESULTS: HIV-1 p24 antigen was detected in 10 of 20 specimens collected from 9 of 12 individuals who seroconverted and in 2 of 2 AIDS patients. HIV-1 plasma RNA was positive in 22 of 22 samples from those 14 individuals. All of 57 diagnostic specimens and 47 samples obtained from persistently indeterminate donors were negative for HIV-1 p24 antigen and plasma HIV-1 RNA. One of 72 blood donor specimens was positive for HIV-1 plasma RNA and had borderline reactivity for p24 antigen. CONCLUSION: The detection of plasma RNA appears to be sensitive and specific; negative test results may be used to identify false-positive serologic reactions. The detection of p24 antigen and plasma RNA can also be used to confirm HIV-1 infection in persons with indeterminate serologic results associated with early seroconversion or late stage disease. PMID- 8191560 TI - Laboratory diagnosis of heparin-associated thrombocytopenia and comparison of platelet aggregation test, heparin-induced platelet activation test, and platelet factor 4/heparin enzyme-linked immunosorbent assay. AB - BACKGROUND: As clinical diagnosis of heparin-associated thrombocytopenia (HAT) is often difficult, confirmation by sensitive laboratory assays is desirable. STUDY DESIGN AND METHODS: The sensitivity of the heparin-induced platelet activation (HIPA) test and the platelet aggregation test (PAT) was prospectively compared by using the sera of 209 patients with the putative diagnosis of HAT. Both assays were performed concomitantly with platelets of the same four donors using a different combination of donors from day to day. Further, all sera were assessed with a platelet factor 4 (PF4)/heparin enzyme-linked immunosorbent assay (ELISA). RESULTS: Positive results were obtained with 33 percent of sera in the PF4/heparin ELISA, with 33.5 percent of sera in the HIPA test, and with 11.5 percent of sera in the PAT. The PF4/heparin ELISA and the HIPA test showed no difference in sensitivity (p = 0.27 by McNemar's test) and were more sensitive than PAT (p < 10(-8) by McNemar's test). However, they recognized different patient cohorts. Nine HIPA-indeterminate and 12 HIPA-negative sera were positive in the PF4/heparin ELISA. Eight of the nine indeterminate sera caused platelet activation with high heparin concentrations in the HIPA test. Eleven of the 12 negative sera contained no IgG, but 9 contained IgM and 2 contained IgA HAT antibodies. Four sera that were indeterminate in the PF4/heparin ELISA and 18 sera that were negative were positive in the HIPA test. None of the sera that were positive in the PAT was missed in the HIPA test, but two of those were negative in the PF4/heparin ELISA. All sera were assessed with four low-molecular weight heparins and a low-molecular-weight heparinoid in the HIPA test with platelets from the same four donors. Low-molecular-weight heparin caused platelet activation with positive sera in 98 percent of tests, and the heparinoid did so in 10 percent; in a further 12.8 percent, crossreactivity to the low-molecular weight heparinoid could not be excluded. CONCLUSION: The majority of HAT antibodies react with a PF4/heparin complex, but there is strong evidence that other antigens are involved in some patients. The HIPA test and the PF4/heparin ELISA are sensitive for diagnosing HAT, and they complement one another. PMID- 8191561 TI - Changing blood use in the AIDS era: the case of elective hip surgery. AB - BACKGROUND: Concern about the transmission of human immunodeficiency virus via blood has substantially increased the public's anxiety about the safety of the blood supply and has encouraged practices to minimize risks deriving from transfusions. STUDY DESIGN AND METHODS: To assess changes in transfusion practices in elective surgery as awareness of transfusion-transmitted human immunodeficiency virus emerged, 80 randomly selected patients per year undergoing elective total hip replacement in five calendar years between 1977 and 1989 at a large university teaching hospital were studied. RESULTS: Total blood use decreased significantly from an average of 3.3 units per patient in 1977 to 2.1 units per patient in 1989 (p = 0.0003). Autologous blood use increased from essentially zero in 1977 to 82 percent of total blood use in 1989 (p < 0.0001). The threshold hematocrit for postoperative transfusion of allogeneic blood (defined by use of logistic regression models) decreased from 30.1 percent (0.30) in 1977 to 26.7 percent (0.27) in 1989 (p = 0.01). As a result of these changes, the proportion of patients exposed to allogeneic blood decreased from 90 to 16 percent across the study period (p < 0.0001). The dramatic decrease in the use of allogeneic blood in elective total hip replacement surgery during the study period was due to decreased demand for blood during and after the operation and to a striking shift in the blood supply from allogeneic to autologous sources. CONCLUSION: These findings demonstrate that physicians can appropriately alter practices when there are perceived health risks. PMID- 8191562 TI - Blood collections by community blood centers, 1988 through 1992. AB - BACKGROUND: The provision of a safe and sufficient supply of blood is critical to patient care. STUDY DESIGN AND METHODS: A survey was conducted of the blood collection activity of the 189 community blood centers operating in the United States from 1988 through 1992. Data were analyzed by source of the donation (allogeneic or autologous), by center's collection volume, and by geographic region. Total collection figures were compared to historical blood collection activity since 1970. RESULTS: A total of 12.31 million units of blood were collected in 1992, an increase of 2.6 percent over the total number of units collected in 1988. For the 5-year period (1988-1992), total collections increased at a compound annual growth rate of 0.6 percent. The collection of allogeneic blood units declined by 0.2 percent annually, while that of autologous units increased by 23.2 percent annually. Autologous blood units accounted for 5.7 percent of total collections in 1992. Nationally, 48 units were collected per 1000 people in 1992, although substantial geographic variation (range, 38-64 units/1000) was observed across nine US census regions. CONCLUSION: The data from this study provide evidence that the total supply of blood grew more slowly from 1988 through 1992 than in the years before 1988. PMID- 8191563 TI - What can we learn about the need for transfusion from patients who refuse blood? The experience with Jehovah's Witnesses. AB - BACKGROUND: A transfusion threshold of 7 g per dL (70 g/L) of hemoglobin has been proposed for patients, although scant human data are available to support this recommendation. STUDY DESIGN AND METHODS: The medical community's experience with Jehovah's Witnesses was examined, in order to assess the lowest tolerable hemoglobin concentration and the lower transfusion threshold of 7 g per dL (70 g/L) of hemoglobin. A MEDLINE search was conducted to capture medical and surgical reports involving Jehovah's Witnesses from 1970 through early 1993. RESULTS: Sixty-one reports of untransfused Jehovah's Witnesses with hemoglobin concentrations < or = 8 g per dL (80 g/L) or hematocrits < or = 24 percent (0.24) were identified. Of 50 reported deaths, 23, as stated in the original reports, were primarily due to anemia. Except for three patients who died after cardiac surgery, all patients whose deaths were attributed to anemia died with hemoglobin concentrations < or = 5 g per dL (50 g/L). Twenty-five survivors were reported with hemoglobin < or = 5 g per dL (50 g/L). CONCLUSION: These data have significant limitations but suggest that survival, without transfusion, is possible at low hemoglobin concentrations, while mortality with an unknown incidence is encountered at hemoglobin concentrations below 5 g per dL (50 g/L). PMID- 8191564 TI - Red cell loss following orthopedic surgery: the case against postoperative blood salvage. AB - BACKGROUND: Expensive devices have been developed for the collection and transfusion of blood salvaged after hip or knee arthroplasty. STUDY DESIGN AND METHODS: The volume of salvaged red cells was measured for the first 6 hours after operation. This volume was compared to total red cell loss during hospitalization and to the volume of allogeneic red cells transfused. RESULTS: Mean postoperative red cell loss in 31 patients following hip replacement was 55 +/- 29 mL and that in 20 patients following knee replacement was 121 +/- 50 mL. The 6-hour wound drainage represented 8.7 and 16.8 percent of overall red cell loss during hospitalization for hip and knee replacement, respectively. The transfusion of postoperatively salvaged red cells would have supplanted transfusion of less than one-third of a unit of allogenic blood after hip replacement and two-thirds of a unit after knee replacement. Only three patients (5.9%) lost red cell volume in the drainage equivalent to or in excess of 1 unit of red cells (180 mL). The volume of red cells salvaged postoperatively bore no relationship to perioperative red cell losses as a whole. CONCLUSION: The relatively small red cell loss in the postoperative period in most arthroplasty patients does not appear to justify the routine use of this technique for the recovery of autologous blood. PMID- 8191565 TI - In vitro characteristics of white cell-reduced single-unit platelet concentrates stored in syringes. AB - BACKGROUND: Platelet concentrates (PCs) for premature infants may be subjected to filtration, centrifugation, and various storage conditions before transfusion. STUDY DESIGN AND METHODS: As there are few data on the cumulative effect of these procedures on PCs, platelet properties (including biochemical and functional in vitro assays) were evaluated after the processing of single units of PCs through a 1-unit-capacity high-efficiency white cell (WBC)-reduction filter followed by syringe storage at either 22 or 37 degrees C for 6 hours. Two- and 5-day-old PCs, volume-reduced PCs, and prestorage WBC-reduced PCs were evaluated. RESULTS: WBC filtration consistently resulted in a 3 to 4 log10 reduction in WBCs, with less than 15-percent platelet loss. No adverse effects of platelet function or evidence of increased platelet activation as determined by the percentage of P selectin positivity were noted. A decrease in pH associated with increased lactate production and consumption of glucose was observed following syringe storage under all conditions tested. Such changes were most pronounced, however, with volume-reduced PCs stored at 37 degrees C (pH 6.31 +/- 0.15, lactate 23.0 +/ 3.06 mmol/L). All pH levels at the end of storage were above the minimum Food and Drug Administration requirement (pH 6.0). CONCLUSION: The in vitro data suggest that single units of PCs can undergo WBC filtration followed by syringe storage for up to 6 hours and still maintain acceptable storage characteristics. The practice of maintaining volume-reduced PCs in syringes for 6 hours at 37 degrees C in isolettes during transfusion should, however, be avoided. PMID- 8191566 TI - Single-base substitutions give rise to a five-banded DNA profile at the D10S28 locus. AB - BACKGROUND: DNA profiles from variable number of tandem repeat (VNTR) loci typically are composed of two bands, one derived from each member of the homologous pair of chromosomes. DNA profiles composed of more than two bands result from mutations, and the question arises as to the mechanism underlying these unusual multi-banded DNA profiles. STUDY DESIGN AND METHODS: An alleged father in a paternity test was found to have a five-banded DNA profile at the D10S28 locus when his DNA was subjected to single-locus restriction fragment length polymorphism mapping with the restriction enzyme Pvu II. RESULTS: Several results suggest that this complex DNA profile is the result of several single base changes within the VNTR locus. First, there was no evidence of partial digestion of the DNA with Pvu II. Furthermore, the multi-banded allele happened, in this case, to be transmitted to the child, who also showed a five-banded pattern composed of four bands inherited from the alleged father and one band inherited from the mother. Second, digestion of this DNA with Hae III resulted in the visualization of just two bands at the D10S28 locus. CONCLUSION: The results confirm the notion that mutations at VNTR loci are not always the result of additions or deletions of tandem repeats, but that they can also involve single base substitutions either within or flanking VNTR loci that give rise to atypical DNA profiles and new alleles at the locus. PMID- 8191567 TI - Effect of amphotericin B and fluconazole on platelet membrane glycoproteins. AB - BACKGROUND: Fever, chills, and reduced platelet recovery may result when platelets are transfused simultaneously with amphotericin B. Amphotericin B reportedly increases the pitting of membranes in stored platelets. STUDY DESIGN AND METHODS: The effects of amphotericin B and another antifungal agent, fluconazole, on platelet membrane glycoproteins (GP) were examined by the incubation of split aliquots of fresh and stored platelet concentrates (PCs) with these drugs for 3 days in storage bags. To determine the effect of storage, PCs were stored for 5 days, and aliquots removed on Days 1 through 5 were placed in platelet storage bags with 4 micrograms per mL of amphotericin B for 2 to 6 hours. Membrane glycoprotein expression was assessed by flow cytometry with fluorescein isothiocyanate-labeled monoclonal antibodies (MoAbs) directed against the following antigens: GPIb (CD42b), CD63 (an activation protein), P-selectin (CD62), and GPIIb/IIIa (CD41a). RESULTS: Amphotericin B produced a concentration dependent decrease in the surface binding of CD42b MoAb with no consistent changes in the binding of CD41a, CD63, or CD62 MoAbs after a 3-day exposure. Stored but not fresh PCs showed decreased binding of MoAb CD42b after a 6-hour exposure to amphotericin B (4 micrograms/mL). Fluconazole produced no changes. When the binding of MoAb CD42b to permeabilized platelets was used to measure total platelet content, amphotericin B (4 micrograms/mL) decreased MoAb CD42b binding to a similar degree in fresh and stored platelets. Inhibition of aggregation to ADP and collagen and ADP and epinephrine was seen in stored but not fresh PCs. CONCLUSION: Therapeutic levels of amphotericin B resulted in partial loss of total platelet GPIb in fresh and stored PCs, but decreased surface expression of platelet membrane GPIb only in stored platelets. This difference between fresh and stored platelets may be related to the limited reservoir of GPIb available for redistribution to the membrane in the previously stored PCs and may account for the decreased recovery of transfused platelets observed in some patients receiving amphotericin B. PMID- 8191568 TI - Fatal outcome in a patient with autoimmune hemolytic anemia associated with an IgM bithermic anti-ITP. AB - BACKGROUND: Several cold autoantibodies (usually IgG) with IT specificity have been reported previously, as have autoantibodies with joint I and P blood group specificities (IP1, ITP1, iP1, IP). A fatal outcome associated with an IgM cold autoantibody of ITP specificity is reported. CASE REPORT: A 54-year-old man suffered from progressively severe cold autoimmune hemolytic anemia for 9 months. Hemoglobin concentration ranged from 6 to 7 g per dL (60-70 g/L) and reticulocytes from 3 to 5 percent (0.030-0.050). The direct antiglobulin test was weakly positive for IgM and strongly positive for C3d. The serum contained a cold agglutinin that reacted strongest with cord i red cells (RBCs) > adult I RBCs > adult i RBCs, which is consistent with IT specificity. The Donath-Landsteiner test was positive; the reaction was neutralized by globoside. The serum reacted weakly or was negative with RBCs from five group p blood donors, which suggests anti-ITP specificity. Dithiothreitol treatment of the serum abolished the cold agglutinin reactivity, which suggests that the anti-IT was IgM. The patient received > 40 RBC transfusions and failed to respond to oral steroids, oral cytoxan, high-dose pulse intravenous steroids, and plasma exchange at room temperature and at 35 degrees C. He died of sepsis following an unsuccessful trial of chlorambucil. Autopsy revealed unsuspected disseminated non-Hodgkin's lymphoma. CONCLUSION: Serologic studies are consistent with our patient's having a single IgM cold autoantibody with IT and P specificities (anti-ITP) and requiring both specificities on the same RBC to permit maximal antibody expression. PMID- 8191569 TI - Fatal graft-versus-host disease associated with transfusions of HLA-matched, HLA homozygous platelets from unrelated donors. AB - BACKGROUND: Transfusion-associated graft-versus-host disease (TA-GVHD) due to blood from HLA-homozygous related and unrelated blood donors has been described. CASE REPORT: Fatal TA-GVHD due to the transfusion of HLA-matched platelets from an unrelated HLA-homozygous donor is reported. A 61-year-old man with a history of diabetes mellitus and myelodysplastic syndrome was diagnosed with acute myelogenous leukemia in November 1991. Induction chemotherapy resulted in aplasia, which was followed by a normocellular marrow with mild dysplasia and continued karyotypic abnormalities. High-dose chemotherapy was given in a second attempt to achieve complete remission. HLA-matched platelets were ordered when platelet refractoriness developed. The patient was HLA-heterozygous for HLA-A and -B antigens (A2, 29; B37, 44). Over the next 7 days, four unirradiated HLA matched plateletpheresis units were transfused; one was probably homozygous for both HLA-A and -B antigens (A2, -; B44, -) and was transfused first, and three were probably homozygous for an HLA-B antigen (A2, 29; B44, -) and were white cell reduced. No blood relatives served as donors. Seven days after the first HLA matched platelet transfusion, fever, chills, and diarrhea developed; 2 days later, a rash was present. Liver enzymes increased markedly. Renal and respiratory failure ensured. A skin biopsy was consistent with GVHD. Despite immunosuppressive therapy, the patient died 19 days after the first HLA-matched platelet transfusion. CONCLUSION: TA-GVHD has been recognized in immunocompromised, HLA-heterozygous patients receiving blood from blood relatives who are HLA-homozygous. patients receiving blood from either blood relatives or non-blood relatives who are HLA-homozygous. This HLA-heterozygous patient received transfusions of unirradiated, class I HLA-homozygous platelets, which were specifically ordered as HLA-matched, and his death was attributed to TA GVHD. Consideration should always be given to providing irradiated blood for immunosuppressed patients, especially when HLA-matched platelets are used, to prevent TA-GVHD. PMID- 8191570 TI - Guidelines for blood utilization review. AB - Hospitals are required by accrediting agencies to perform blood utilization review. Specific areas that must be addressed are the ordering, distribution, handling, dispensing, and administration of blood components. Monitoring the effects of transfusion on patients is also required. The format of the review process and the criteria for appropriate blood utilization must be developed by each institution. This article provides examples of areas that can be reviewed and procedures that may be used. However, the suggested laboratory values must not be interpreted as defining indications or criteria for transfusion. Each transfusion committee, or its equivalent, is responsible for developing its own institutional blood utilization procedures and audit criteria. Review and approval by the medical staff prior to implementation are essential. The procedures must also be reviewed and revised on a regular basis. PMID- 8191571 TI - Platelet refractoriness and alloimmunization are not necessarily synonymous. PMID- 8191572 TI - Human T-lymphotropic virus type I (HTLV-I) DNA in an HTLV-I-endemic area (Miyazaki, Japan) PMID- 8191573 TI - Perioperative blood transfusion and colorectal cancer recurrence. PMID- 8191574 TI - An improved method for white cell counting in white cell-reduced red cells. PMID- 8191575 TI - Score on a four-antigen recombinant immunoblot assay (RIBA-2) and hepatitis C virus RNA detection in RIBA-2-indeterminate blood donors. PMID- 8191576 TI - A study of the prevalence and patterns of inheritance of partial D antigen category VI in a white donor population. PMID- 8191577 TI - Autologous blood donation is a contradiction in terms. PMID- 8191578 TI - Conversion of group A red cells by deacetylation to ones that react with monoclonal antibodies specific for the acquired B phenotype. PMID- 8191579 TI - Decrease in transfusion-associated graft-versus-host disease. PMID- 8191580 TI - Current utilization of the direct antiglobulin test investigation: results of a hospital survey. PMID- 8191581 TI - Genes for normal and diseased mental states. PMID- 8191582 TI - A simple and rapid method for separating co-cloned YACs. PMID- 8191583 TI - Simultaneous determination of cell surface antigens and apoptosis. PMID- 8191584 TI - The 3Rs of life: Ras, Raf and growth regulation. AB - Cellular Ras proteins are essential elements in normal signal transduction pathways while activated Ras proteins are prevalent in many different forms of human cancers. Here, we discuss the mechanism through which Ras proteins, either cellular or activated, transmit a proliferative signal by activating cytoplasmic serine/threonine kinases. PMID- 8191585 TI - Patterning in the C. elegans embryo. AB - Recent studies reveal preliminary insights into the mechanisms of embryonic patterning in Caenorhabditis elegans. It appears that both embryonic axes and early blastomere fates are determined by a combination of segregating determinants and cell interactions, under the control of maternally expressed genes. Later in embryogenesis, some regional identities are specified by a group of homeotic selector genes homologous to the HOM-C clusters in other animals. Intervening stages of specification, which could link these two classes of genes in a regulatory hierarchy, are beginning to be investigated. PMID- 8191586 TI - Phosphotyrosine phosphatases with SH2 domains: regulators of signal transduction. AB - Among the rapidly growing family of protein tyrosine phosphatases (PTPs), a subfamily of cytoplasmic PTPs that contain SH2 domains has been identified in both mammals and Drosophila. These PTPs each contain two tandem SH2 domains at their amino-terminus, and a single phosphatase domain. The SH2-containing PTPs appear to be downstream targets of growth factor receptor tyrosine kinases, and have been shown genetically to be required for normal development in Drosophila and in the mouse. Accumulating biochemical and genetic data therefore suggest that SH2-containing PTPs might have a physiological role in intracellular signal transduction. PMID- 8191587 TI - Moving right along: regulation of cell migration during Drosophila development. AB - Cell movement is a fascinating feature of animal development. Genetic approaches have recently led to the identification of regulatory proteins required for specific cell migrations in development of the mouse, nematode and fruit fly. Here, I focus on two model systems for genetic studies of cell migration during Drosophila development: migration of follicle cells in the ovary and migration of tracheal cells in the embryo. Mutations that affect these migrations have allowed the identification of transcription factors and an FGF receptor homolog as important regulators of cell migration. Signaling through receptor tyrosine kinases may be a general mechanism for the regulation of cell movement in development and in metastasis. PMID- 8191588 TI - Exopolysaccharides of Rhizobium: synthesis, regulation and symbiotic function. AB - Exopolysaccharides of Rhizobium have long been suspected, and are now known, to function in the Rhizobium-legume root nodule symbiosis. Recent studies have enhanced our knowledge of these extracellular polymers as symbiotic signals and have elucidated their biosynthesis and regulation. PMID- 8191590 TI - Medical management of colorectal carcinomas. AB - Current information on the medical treatment of colorectal cancer was reviewed after a search of the literature through Medline. Publications from 1984 to present were surveyed. Appropriate adjuvant therapy increases overall survival and disease-free intervals. The treatment modalities of unresectable or metastatic tumors are disappointing, with at best 40% of patients experiencing short-lasting responses. Whenever possible, patients with advanced colorectal cancer should be enrolled in clinical trials. PMID- 8191591 TI - Cancer mortality in Italy, 1990. PMID- 8191592 TI - Cancer mortality in Italian migrants to Canada. AB - The present study reports on the analysis of cancer mortality in Italian first generation migrants resident in Canada, deceased in the period between 1964-1985 (5,801 males: 3,267 females). Mortality in migrants is compared to that of the host population as well as to that in the migrants' country of origin. This is carried out both on a national level (Italy), and on a regional level with those regions that have made the greatest contribution to the Italian migratory flow (Southern Italy). Compared with the Canada-born population, significantly higher risks were evident for nasopharynx, stomach, liver and gallbladder tumors in migrants. Lower risks were observed for the oral cavity, esophagus, colon, rectum, pancreas (females), larynx, lung, melanoma, breast, ovary, prostate, bladder (females), and non-Hodgkin's lymphoma in migrants. This is consistent with that evidenced in the comparison between Italy and Canada. The data are discussed in relation to the results of other studies on Italian migrants and the prevalence of main risk factors. PMID- 8191593 TI - What do Italian hospital physicians know about quality of life assessment in oncology? AB - AIMS: To assess the current level of information and use of quality of life assessment instruments by Italian physicians involved in oncologic patient care. METHODS: Specifically trained scientific representatives of a pharmaceutical company interviewed 2237 hospital physicians all over Italy. RESULTS: A total of 1390 physicians (62.1%) had some knowledge of quality of life assessment tools in oncology, but 364 of them (26.2%) were unable to recall the name of any instruments. The one that was most frequently recalled by the 1026 physicians who knew of the existence of one or more instruments was the Karnofsky Performance Status (KPS) (91%) followed by the Eastern Cooperative Oncology Group performance scale (ECOG) (35.5%) whereas the Quality of Life Index and Visual Analogue Scale were at the very bottom of the list (5.9% and 3.7%, respectively). Physician age and type of department were found to be strong predictors of knowledge of the instruments, which was greater among young physicians and those working in oncological departments. Of the physicians aware of the KPS, 56.6% used it, whereas the percentage of physicians using ECOG was higher (69.5%). CONCLUSIONS: The collected data indicate a poor knowledge of quality of life assessment instruments in Italian physicians. Most physicians tend to use so-called << objective >> instruments where the assessment is made by the physician and not by the patient (KPS, ECOG Quality of Life index), are practically unaware of the new generation of "subjective" self-rating instruments. The use of such instruments in particular might provide greater insights into the impact of the disease and related treatments on the quality of life of cancer patients. PMID- 8191594 TI - Ovarian function suppression with the gonadotrophin-releasing hormone (GnRH) analogue goserelin in premenopausal advanced breast cancer. AB - AIMS AND BACKGROUND: Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue that induces the suppression of gonadal steroidogenesis, and it could therefore be a medical alternative to irreversible surgical castration. We report the clinical and endocrine results from 40 goserelin-treated premenopausal patients with advanced breast cancer. METHODS: A depot formulation of the drug (3.6 mg s.c.) was administered fortnightly for the first 4 doses, and monthly thereafter. Gonadotrophins and estradiol (E2) levels were measured before and at specific times during the treatment. RESULTS: Objective responses were observed in 17 of the 38 evaluable patients (45%), six of whom achieved complete remission. The best responses were observed on soft tissues (65%). Castration E2 levels were achieved in all of the patients. CONCLUSIONS: Our results confirm that goserelin is as effective as surgical oophorectomy in premenopausal advanced breast cancer. PMID- 8191595 TI - Mitomycin "C" and vinorelbine as second line chemotherapy for metastatic breast carcinoma. AB - AIMS AND BACKGROUND: Patients with metastatic breast carcinoma resistant to first line chemotherapy may require further treatment. Results o second line chemotherapy are still largely unsatisfactory. For this reason a phase II study on the combination of mitomycin C and vinorelbine was carried out. METHODS: Forty patients with anthracycline pretreated metastatic breast cancer were treated with a combination of mitomycin C 10 mg/m2 i.v. on day 1, and vinorelbine 25 mg/m2 i.v. on days 1 and 8. This cycle was repeated every 28 days. Responses were evaluated according to the WHO criteria. RESULTS: A major objective response was recorded in 16 cases (40%; 95% confidence limits 32%-48%), with 2 patients (5%) obtaining a complete response with a median duration of 8.0+ months, and 14 (35%) a partial response with a median duration of 7.3+ months. Nine patients (23%) showed no change, and 15 progressed. Patients who did not meet the minimal required criteria to be evaluable were considered as treatment failures. Responses were seen at all sites of disease, but skin, nodal, and soft tissue lesion were more chemosensitive than liver, lung, and bone ones. The mean survival of patients with complete and partial responses was 8.9+ months, whereas that of patients with no change or progressive disease was 7.8 and 6.0 months respectively. Treatment was very well tolerated by most patients. Gastrointestinal toxicity was mild. Grade 2 leukopenia was recorder in 45% of patients, and grade 3 leukopenia in only 10%. Grade 2 thrombocytopenia was seen in 5%. Reversible mild to moderate constipation occurred in 45%, but no case of severe neurotoxicity was observed. CONCLUSIONS: Our data suggest that the combination of mitomycin C and vinorelbine is active in metastatic breast carcinoma refractory to first line chemotherapy containing anthracyclines, and may be safely administered on an outpatient basis. PMID- 8191597 TI - Carcinoma of the external auditory meatus and middle ear. Results of the treatment of 28 cases. AB - AIMS: The authors report their experience on the treatment of 28 cases of middle ear (3) and external auditory meatus (EAM) cancers (25) with surgery and/or radiation therapy. According to histologic type, there were 23 squamous cell carcinomas, 4 basal cell carcinomas and 1 adenocystic carcinoma. METHODS: Surgery alone was performed in 2 cases, surgery combined with radiotherapy in 11 cases, and radiotherapy alone in 15 cases. Postoperative radiation therapy dose ranged between 4500 and 5500 cGy; the definitive dose was 6000-7000 cGy. The median follow-up was 61 months. RESULTS: Complete response rate 6 weeks after the end of the treatment, evaluated by CT scan, was 85.7% (24/28). Definitive local control was obtained in 20/28 cases for the primary site and in 26/28 cases for the neck. Nine of the 10 recurrences were retreated with low-dose radiotherapy combined with surgery, chemotherapy or hyperthermia. A new local control was obtained in 2 cases. Four patients were lost during the follow-up at 13, 14, 17 and 23 months after the end of the treatment. The survival rate was 54% (13/24); disease-free survival was 50% (11/22). CONCLUSIONS: Despite a not very aggressive treatment, our results are quite good. PMID- 8191596 TI - Intra-arterial hepatic carboplatin-based chemotherapy for ocular melanoma metastatic to the liver. Report of a phase II study. AB - AIMS AND BACKGROUND: ocular melanoma tends to metastasize to the liver, sparing for a long time the rest of the organism. Therefore, a regional treatment is especially indicated. METHODS: eight patients with ocular melanoma metastatic to the liver were treated with intra-arterial hepatic carboplatin-based chemotherapy at the dose of 300 mg/m2 once every two weeks at an out-patient clinic. All the patients were submitted to laparotomy with surgical implantation of an arterial port device through the gastroduodenal artery. RESULTS: the overall response rate was 38% with a median survival time of 15 months. The regimen was well tolerated and the principle toxicity was myelosuppression; any instance of hepatic and/or cholangitic damage was reported. CONCLUSIONS: Carboplatin seems suitable for intra-arterial hepatic chemotherapy and active in ocular melanoma metastatic to the liver. PMID- 8191598 TI - High-dose interstitial brachytherapy for glioblastoma multiforme. AB - AIMS AND BACKGROUND: The long-term prognosis for survival of patients with inoperable glioblastoma multiforme (GBL) is very poor. Conventional external radiotherapy gives only transitory result. This severe prognosis led us to elaborate a high-dose rate (HDR), after-remote-loading brachytherapy treatment protocol: our aim was both therapeutic and psychologic. METHODS: Five patients with GBL (T1 G4 UICC) were treated with stereotactic biopsy followed by HDR brachytherapy. A unique coaxial after-loading catheter was stereotactically inserted through the center of the target volume. The treatment schedule considered 5 fractions, 5 Gy/fraction at the dose specification surface, 2 fractions per day. RESULTS: The treatment was well tolerated. Tumor progression started again at the 8th to the 16th week from the end of the treatment. ECOG performance status at the 8th week was better than before the therapy in 2 of 5 patients and was stable in 2 of 5 patients. Order neuroperformance status was stable in 2 patients at 8 weeks. At the 16th week there was neurologic deterioration. The average survival was 21 weeks. CONCLUSIONS: Our approach seems to be of some interest for the palliation of GBL, and it offers some advantages, in particular regarding the short treatment period. Our procedure can be improved: a multi-catheter implant and a more fractionated schedule could be taken into account. PMID- 8191599 TI - Relation between ovarian carcinoma-associated antigens in tumor tissue and detached cyst fluid cells of patients with ovarian neoplasms. AB - AIMS: The expression and potential diagnostic value of ovarian carcinoma associated antigens were estimated in different types of epithelial ovarian neoplasms. The comparison of antigenic expression was performed on solid tumor tissues and loose cyst fluid cells in individual cases of malignant and benign ovarian neoplasms. METHODS: All studies were performed using monoclonal antibodies (mAbs) against ovarian carcinoma-associated antigens (OC125, OV-TL3, OV632, 10B, 8C) by 3-step peroxidase-antiperoxidase test. RESULTS: All ovarian carcinoma-associated antigens were detected in most serous and endometrioid carcinomas. In mucinous carcinomas as well as in benign ovarian neoplasms these antigens were present only in some cases. Significant inter- and intratumoral immunological heterogeneity was evident; however, the antigens detectable in tissue sections were also found in detached cyst fluid cells. CONCLUSIONS: Our results show that mAb show OV-TL3 is the best marker for endometrioid carcinomas and confirmed that mAbs OV632, OC125 and OV-TL3 could be good complementary markers for differentiating malignant and benign lesions in the ovary. The percentage content of all ovarian carcinoma-associated antigens in solid tumors and respective cyst fluid cells was comparable. PMID- 8191600 TI - Epidermal growth factor receptor and estrogen and progesterone receptors in breast cancers of premenopausal and postmenopausal patients. AB - AIMS AND BACKGROUND: The purpose of our research was to investigate the relations between the levels of epidermal growth factor receptor and estrogen and progesterone receptors in breast cancers of premenopausal and postmenopausal Polish women. METHODS: Cell membrane levels of epidermal growth factor receptor (EGF-R), and cytosol (c) estrogen (ER) and progesterone (PR) receptors were determined in 221 specimens of primary breast cancers. ERc and PRc were assayed using the dextran-coated charcoal procedure, and EGF-R were assayed by the radioligand method of specific saturation of the crude membrane fraction with 125I-EGF RESULTS: A statistically significant inverse correlation was found in all tumors between the concentrations of EGF-R and ERc, whereas for PRc significance of this correlation was not fully confirmed. ERc concentrations in tumors were positively correlated with age of patients, whereas EGF-R and PRc were not. In all, in premenopausal, and in postmenopausal EGF-R-positive tumors (> or = 10 fmol/mg of membrane protein), mean concentrations of ERc did not differ significantly. These groups of tumors seem to be homogeneous with respect to ERc concentrations. In EGF-R-negative (< 10 fmol/mg of membrane protein) postmenopausal tumors, the mean ERc concentration was significantly higher than in premenopausal tumors, hence these groups of tumors appear to be heterogeneous with regard to ERc contents: CONCLUSIONS: The present findings may have significance in differentiation of postmenopausal breast cancer. PMID- 8191601 TI - Teratoid Wilms' tumor. A unilateral case. AB - A unilateral teratoid Wilms' tumor in a 3-year-old girl is presented. Histopathologic features of this rare variety, differential diagnosis and effects of chemotherapy are discussed in light of other reports in the literature. PMID- 8191602 TI - Ossifying fibroma of the skull: clinical and therapeutic study. AB - AIMS AND BACKGROUND: Ossifying fibroma is a tumor with benign course that rarely affects the cranial bones. METHODS: The authors report 5 cases of ossifying fibroma of the skull and analyze the clinical course and treatment of this lesion. RESULTS: 3 patients were females and 2 males. The mean clinical history was 3.2 years. 4 patients underwent total removal and 1 partial. At mean follow up of 19 years, all patients who underwent total removal showed improvement of neurological deficit, whereas the patient who underwent partial removal had clinical regrowth. CONCLUSION: The authors conclude that total removal of fibroma should be extended to normal bone and in cases in which total removal is not possible the residue should be checked for regrowth by serial MRI. PMID- 8191603 TI - The impact of mothers' health education on the prevalence of acute respiratory infections in children. AB - In this study, the effects of educating mothers on acute respiratory infections were investigated in Hacilar district of Kayseri, a province in Central Anatolia. The intervention group included 69 children and the control group 57 children between the ages of 0 and 4 years. The children in both groups were checked for symptoms of acute respiratory infections (ARI) in January 1990 and 1991, before and after intervention. The intervention consisted of 30 minutes of face-to-face education of mothers regarding ARI prevention and treatment. In addition, the numbers of clinic visits by children for acute infections before and after intervention were compared. The prevalence of acute respiratory infections decreased from 49.3% to 27.5% in the intervention group and from 43.9% to 38.6% in the control group. The decrease in the prevalence of acute respiratory infections in the intervention group differed significantly, from that of the control group. On the other hand, clinic visits by the intervention group for acute respiratory infections increased significantly. PMID- 8191604 TI - Epidemiology in pediatric anesthesia. A computerized survey of 10,000 anesthetics. AB - The practice of anesthesia in 10,000 children was analysed and evaluated with the aid of Epi-Info, Version 5. There were 545 newborns, 1573 infants, 3147 children between the ages of 1 and 5 years, and 4735 children between the ages of 6 and 15 years. Female:male ratio was 1:1.9. In 92% anesthesia was provided for surgical and in 8% for diagnostic procedures. The most common sites of surgery were head and neck (19%), eye (12%), genitalia (9%) and inguinal region (8%). The type of admission was elective in 76%, emergency in 16% and outpatient in 8% of patients. The distribution within the ASA classes was 92% in I, 4% in II, 2.7% in III and 1.1% in IV+V. Premedication was given to 66% of cases. 98.5% had a general anesthetic and the remaining were given regional blocks. Induction was carried out with intravenous agents in 59% and maintenance with inhalational agents in 92%. The use of muscle relaxants was 82%, mainly succinylcholine followed by vecuronium. Endotracheal intubation was done in 86% of cases, with serious difficulties in 1.3%. 91% of the newborn babies were intubated, 2.8% with difficulty. 9.2% had blood transfusions. There were serious complications in 4.4% and 28 cardiac arrests, of which 20 were successfully resuscitated. Epi-Info, Version 5 was found satisfactory for epidemiological analysis and evaluation in anesthesia, and the information obtained with its aid was discussed in light of published data. PMID- 8191605 TI - Congenital nasolacrimal duct obstruction in Kayseri, Turkey. AB - Congenital nasolacrimal duct obstruction was diagnosed in 170 patients between 1982 and 1991 in Kayseri, Turkey, and 111 patients were treated with massage plus topical antibiotics (MBC), pressure irrigation (PI), probing (PRB) or infracturing of the inferior turbinate (INF). The ages of the patients ranged from one week to 15 years. The obstruction was bilateral in 38 patients. Among the 149 obstructed lacrimal drainage systems of 111 patients, 101 were cleared by MBC (67.8%), 30 by PI (20.1%), eight by PRB (5.3%) and two by INF (1.3%). Eight cases were unsuccessful (5.3%), and the overall success rate was 94.6%. The efficacy of four interventions was correlated to the patients' ages and to the presenting pathology. MBC carried out at the serofibrinous stage and at 7-13 months was more effective than other interventions, with a statistical significance (p < 0.01). The effectiveness of four interventions is discussed, with an emphasis on the importance of early MBC. The importance of fluoroscopy during PI or PRB is also emphasized. PMID- 8191606 TI - Ocular involvement in childhood leukemias. AB - Ocular involvement was detected in 36 of 84 children suffering from acute leukemia. The major manifestation of leukemic ophthalmology was retinal hemorrhage. Neither platelet counts nor hematocrit values correlated with the occurrence of hemorrhages. As the eye is a pharmacologic sanctuary, it is emphasized that full ophthalmologic evaluation of leukemic patients is a critical part of their follow-up and will guide the choice of therapeutic regimen. PMID- 8191607 TI - Long-term use of anti-D in chronic idiopathic thrombocytopenic purpura. AB - Chronic idiopathic thrombocytopenic purpura is an autoimmune disease characterized by antibody-mediated destruction of platelets. To maintain the platelets above the symptomatic level, we administered anti-D (100 micrograms for 5 consecutive days) in 19 children with idiopathic thrombocytopenic purpura (ITP). Four patients did not respond to treatment. Fifteen responded with an increase in the average platelet number to 76,000/microL on the 7th postinjection day. Within 45 days, however, platelets dropped to 27,000/microL. Three months after this study, two patients from the study group were re-administered anti-D in daily injections for 5 consecutive days, as was done previously. Monthly administration of anti-D in two patients maintained platelets above 30,000/microL for periods of five and six months. We concluded that monthly administration of anti-D after five consecutive daily injections can maintain platelet levels above the symptomatic level and may provide a corticosteroid-free safe interval of nearly five months. PMID- 8191608 TI - Violence: a growing danger to children. The American case. AB - A frightening, growing epidemic of senseless, irrational and inexcusable violence has seized the United States. While it involves all ages and localities, the occurrences are predominantly in areas of poverty, poor housing and unemployment. Children, particularly the adolescent and young adult male black population, are at greatest risk. There are recognized many contributing forces such as low self esteem, family disruption and single parenting. Country-wide there is easy access to guns and lack of gun safety guards. Violent television sets an example for our youth and lends an air of adventure and excitement to their lives. The solution to this enormous problem is clearly not an easy one and must be through a combination of many social and legal changes. This is most assuredly a medical problem and demands thought and active participation by physicians. There are a number of strategies for physicians, especially pediatricians. We must look carefully at family interactions, attempting to promote more kindly behaviors, enhance self-esteem. School-age children can be helped through office discussions and collaboration with teachers. "Leave the knives and guns at home, avoid noisy arguments, use more kindly words." "Television is not real life; the actors do not die." These are our people. Their needs are great. We must help. PMID- 8191609 TI - Subacute necrotizing encephalopathy (Leigh syndrome): report of two juvenile cases with fatal outcome. AB - The clinical and pathological findings of two children diagnosed on autopsy with subacute necrotizing encephalopathy (SNE) are presented. One of the patients was a previously healthy 12-year-old boy with a rapid clinical course and fatal outcome. The second case was a mentally retarded 13-year-old girl with a positive family history of neurological disease and progressive deterioration. Brain edema, bilaterally symmetric gray-brown areas of spongy degeneration and cavity formation were present in the basal ganglia in both cases. A small cavity was noted in the right inferior olive in Case 2. Mamillary bodies were spared in both cases macroscopically and microscopically. Microscopic sections of the involved areas and the periaqueductal region in Case 2 exhibited variable degrees of necrosis, spongiosis with a striking proliferation, and dilatation of the capillaries. Similar changes were noted in the cerebral cortex of Case 1. Microglial and astrocytic proliferation with some loss of myelin were also noted. The neurons, although reduced in number, were frequently preserved within the lesions. To our knowledge, only three patients over two years old have been reported in the literature with an acute clinical course and a fatal outcome. Case 1 is the fourth such case. PMID- 8191610 TI - Perforated duodenal ulcer: an unusual complication of meningitis. AB - An 11-month-old boy was admitted to the hospital with fever, vomiting and seizures and was diagnosed with purulent meningitis. Two days later, an acute, perforated, duodenal ulcer was detected in the patient. Surgery was performed, and the patient made an uncomplicated recovery. Peptic ulceration is underdiagnosed in children and this leads to delay in diagnosis and appropriate management. Peptic ulceration may occur during severe illness or viral infections, but perforation is rare. PMID- 8191611 TI - Effect of exchange transfusion on elimination of antibiotics in premature infants. AB - Although the use of exchange transfusion has become routine in intensive care nurseries, little information is available on drug loss resulting from exchange transfusion. The aim of this study was to review the effect of exchange transfusion on the elimination of some antibiotics in premature infants according to the recent pharmacokinetic data. A pharmacokinetic equation was used to estimate drug loss from the body by exchange transfusion. Our data suggest that exchange transfusion can significantly decrease the serum concentrations of antibiotics with smaller volumes of distribution, but the drug loss of antibiotics with larger volumes of distribution can be acceptable. PMID- 8191612 TI - Transorbital stab wound: a case report. AB - Stab wounds of the skull are uncommon. They are usually accidental in children. An apparently trivial wound may cause death due to vascular damage or infection. A 5-year-old boy presented with a nail in the left intraorbital region. He fell with a nail in his hand five hours prior to hospital admission. Computed tomographic scans displayed the nail penetrating the cranium through the left orbital roof and extending towards the left anterior clinoid process. The nail was removed under general anesthesia in the operating room. Meningitis developed two days after the removal of the penetrating object and responded well to antibiotics. The pertinent literature was reviewed. PMID- 8191613 TI - Ureteral injury due to Kirschner wire in a five-year-old girl. A case report. AB - Traumatic injury to the ureter in childhood is uncommon, and since it is not associated with hematuria may remain undiagnosed for a relatively long period of time. In this paper we reported the case of a five-year-old girl who had ureteral injury due to Kirschner wire application for hip dislocation. We drew attention to the fact that pelvic interventions may be complicated by ureteral injury, and intravenous pyelography to a useful tool to reach the final diagnosis. PMID- 8191614 TI - Multiple sclerosis in a six-year-old boy (case report). AB - A 6-year-old boy with multiple sclerosis, youngest diagnosed in our hospital, is presented. In addition to the clinical findings, the diagnosis was supported by increased immunoglobulin levels, positive IgG index and oligoclonal bands in the cerebrospinal fluid, normal cranial angiography, typical lesions on the cranial computed tomography and magnetic resonance imaging. PMID- 8191615 TI - Immunoglobulin light chains and the kidney: an overview. AB - Monoclonal immunoglobulins and free immunoglobulin light chains are produced by plasma cells as a result of their clonal expansion in plasma cell dyscrasia. These proteins are pivotal in the development of pathologic and clinical symptoms of plasma cell dyscrasia and renal manifestations are frequently the presenting and leading features of this process. The spectrum of pathology associated with monoclonal light chains includes light-chain cast nephropathy and tissue deposits derived from the monoclonal light chain, ie, amyloid derived from the light chains and nonamyloidotic light chain deposition disease. The main diagnostic features, differential diagnosis, and pathogenesis are briefly reviewed. PMID- 8191616 TI - Myoglobin and the kidney: an overview. AB - The toxic effects of myoglobin on the kidney are discussed. Pathophysiologic mechanisms involved in myoglobinuric conditions associated with renal dysfunction as well as important diagnostic laboratory and morphologic considerations are addressed. The subject is placed in proper clinicopathologic perspective by discussing the most common clinical situations involved. PMID- 8191617 TI - Light chain deposition disease (nodular glomerulopathy, kappa light chain deposition disease): a case report. AB - A typical case of kappa light chain deposition disease is detailed. Clinical and pathological findings are described. The discussion focuses on the diagnostic challenges encountered in the diagnosis of monoclonal light chain-related renal diseases. Experimental models have played a relevant role in clarifying and elucidating fundamental questions of diagnostic significance. PMID- 8191618 TI - Myoglobinuric acute renal failure associated with cocaine use. AB - A case of a young muscular male presenting in anuric acute renal failure after cocaine use with a distal obstructive nephropathy by myoglobin casts is presented. Insights into cocaine metabolism, adverse effects, and interaction with alcohol, diagnostic considerations, and mechanisms involved in renal damage are addressed. PMID- 8191619 TI - beta 2-Microglobulin amyloidosis: illustrative cases. AB - Patients on long-term dialysis tend to develop amyloidosis derived from beta 2 microglobulin. Serum levels of this protein rise in renal insufficiency and remain high in patients on dialysis. The distribution of amyloid deposits in such patients as well as tissue diagnosis, immunohistochemistry, and electron microscopic features are briefly discussed. PMID- 8191620 TI - Glomerulocystic disease and lupus glomerulonephropathy. AB - A renal biopsy demonstrated the presence of both glomerulocystic disease (GCD) and lupus glomerulonephropathy in a patient who was admitted for an unrelated disease and was found to have proteinuria and renal failure. Of 12 adult patients with GCD reported in the literature, some form of glomerulonephropathy was demonstrated in 3. One of the 3 had the membranous type of lupus glomerulonephropathy. When family members of previously reported cases of GCD have been examined, "occult" cases of GCD were frequently identified. GCD is probably a much more frequent disease than the relatively small number of published cases would lead one to believe. In adults GCD is often asymptomatic and will only become symptomatic if another renal disease, such as lupus glomerulonephropathy, is superimposed. PMID- 8191621 TI - Peculiar membranogranular glomerular deposits. AB - Two patients with immune complex diseases, one with IgA nephropathy and the other with systemic lupus erythematosus, were found to have peculiar membranogranular deposits in the glomeruli in addition to typical immune complex deposits. There was no clinical indication of familial lipodosis in either case. The deposits were very similar to those seen in lecithin-cholesterol acyltransferase-deficient patients. The pathogenetic role of lipid deposits in the glomerulus is discussed. PMID- 8191622 TI - Demyelinative process associated with atypical intranuclear glial inclusions. AB - This case study documents a demyelinating process associated with atypical glial intranuclear inclusions. The patient, a 38-year-old woman, presented with acute onset of headaches and weakness. Magnetic resonance imaging revealed two discrete intrahemispheric lesions. Light microscopic examination showed small, homogeneous, eosinophilic inclusions chiefly in astroglial nuclei. By electron microscopy these inclusions were shown to be clusters of filamentous structures. Attempts to identify the particles with an antibody to measles virus and in situ hybridization to JC virus were negative. The morphologic appearance of the inclusions in this case is similar to that described in neuronal intranuclear inclusion disease. PMID- 8191623 TI - Ultrastructural markers in the pathologic diagnosis of pituitary adenomas. AB - The functional-morphologic classification of pituitary adenomas increased the number of distinguishable morphologic entities from 3 (acidophilic, basophilic, chromophobic) to 15. Identification of tumor types requires histology as well as immunohistochemistry and electron microscopy. Electron microscopy has a pivotal role in the recognition and separation of entities with overlapping immunohistochemical profiles. Electron microscopic diagnosis is facilitated considerably by structural markers present in the majority of adenoma types. Two groups of ultrastructural markers are discussed. Organelle markers are represented by specific morphology/arrangement of ubiquitous cytoplasmic constituents (rough endoplasmic reticulum, Golgi apparatus, mitochondria). Special markers are usually restricted to a particular pituitary cell type, its tumors, or both (filamentous aggregates, particular morphology of secretory granules, etc). Evaluation of general ultrastructural features and identification of structural markers permit conclusive diagnosis in the majority of pituitary adenomas. Cell derivation remains uncertain in many so-called clinically nonfunctioning adenomas with no or insufficient markers and poorly developed cytoplasmic organization associated with low endocrine activity. PMID- 8191624 TI - Ultrastructure of adrenal cortical carcinoma. AB - The ultrastructural features of 30 adrenal cortical carcinomas have been reviewed and compared with those seen in adrenal cortical adenomas, adrenal cortical hyperplasia, and the normal cortex. A broad range of ultrastructural appearances was found among the carcinomas, but the differences were mainly in the amount of cytoplasmic lipid, number of lysosomes, and quantity and architecture of the mitochondria and endoplasmic reticulum. Structural variants among the carcinomas included lipid-rich, oncocytic, and glycogen-rich cells. Electron microscopy can be extremely useful in differential diagnoses that include adrenal cortical carcinoma. PMID- 8191625 TI - Tubular inclusions in macrophages in the brain of a patient with acute hemorrhagic leukoencephalitis (Weston-Hurst syndrome). AB - A case history, biopsy findings, and autopsy findings of an unusually long lasting case of acute hemorrhagic leukoencephalitis in a young woman are presented. Diagnosis by stereotactic biopsy of brain lesions seen on computed tomography and magnetic resonance imaging scans had been attempted previously. On histologic examination the biopsy showed sheets of macrophages, which were found to contain unusual tubular inclusions on electron microscopy. The nature of these inclusions is discussed. PMID- 8191626 TI - Aggressive small cell tumor of the skull base. AB - A 40-year-old Black man presenting with increasing nasal discharge of bloody, mucoid pus as well as nasal obstruction over a 2-month period is described. Magnetic resonance imaging of the skull showed a tumor eroding through the skull base into the clivus and extending into the sphenoid sinus. Endoscopy of the sphenoid sinus demonstrated a polypoid mass extending into the posterior choanae. The lesion was partially resected. Histologic evaluation showed a cellular small blue cell tumor punctuated by bland, epithelial-lined microcysts. Electron microscopy revealed epithelial cells with abundant rough endoplasmic reticulum and electron-dense membrane-bound endocrine granules, some undergoing misplaced exocytosis. Immunohistochemical evaluation demonstrated cytoplasmic reactivity for neuron-specific enolase, synaptophysin, and prolactin. Stains for leukocyte common antigen, HMB-45, desmin, cytokeratin, chromogranin, and the remaining spectrum of pituitary hormones including growth hormone, corticotropin, luteinizing hormone, follicle-stimulating hormone, and thyrotrophic hormone were negative. In contrast, the epithelium lining the cysts was cytokeratin positive and synaptophysin negative. This ostensibly small cell tumor therefore represented a remarkably extensive and aggressive prolactin cell adenoma with unusual light microscopic features. Characterization of the lesion required electron microscopy and further confirmation by immunocytology. The distinction of pituitary adenomas and particularly of prolactin cell tumors from other adenoma types and from other small cell lesions markedly affects therapy and patient prognosis. PMID- 8191627 TI - Utility of ultrastructural studies of cardiac biopsy specimens. PMID- 8191628 TI - Assessment of anthracycline cardiomyopathy by endomyocardial biopsy. AB - Ultrastructural evaluation of endomyocardial biopsy specimens is a sensitive and effective method with which to detect and quantitate cardiotoxicity produced by anthracylines. The procedure and grading system used at the M.D. Anderson Cancer Center are described, and some of the pitfalls that may be encountered by the electron microscopist are reviewed. PMID- 8191629 TI - Ultrastructural findings in cardiac transplant recipients. AB - Ultrastructural findings in 350 endomyocardial biopsy specimens and 59 autopsy or explanted hearts from cardiac transplant recipients are reviewed. Myocyte degeneration can be readily distinguished from necrosis by the technique described. Vascular changes of endothelial activation, endothelial cell damage, and basement membrane reduplication can be readily identified. In addition, the myofilament composition of ischemic hearts in patients with allograft coronary artery disease is distinctive: There is a disproportionate loss of actin over myosin, giving a coarse appearance to the myofilaments. These changes are useful in further defining the morphologic features associated with rejection and ischemia in cardiac transplant recipients. PMID- 8191630 TI - Focal ellipsoid deposits in the atrial myocytes of Syrian hamster. AB - A peculiar hyaline sarcoplasmic inclusion in the atrial myocytes of old female Syrian hamsters is described. This type of inclusion resembles that described in rare human cardiomyopathy. They have also been described in other rodents and have been speculated eventually to contain atrial natriuretic factor (ANF). The present study demonstrated that they are fibrillar in nature, however, and do not contain ANF-immunoreactive product. Because their morphologic aspect is analogous to that described in human heart and in the pathology of other contractile tissues, it is suggested that they probably consist of intermediate filaments and/or associated macromolecules. PMID- 8191631 TI - Cardiac paraprotein associated with Waldenstrom's macroglobulinemia: a case report. AB - A case of myocardial paraprotein deposition in a patient with Waldenstrom's macroglobulinemia is presented. Routine light microscopy revealed diffuse widening of interstitial regions by pale eosinophilic material that had a grayish cast on trichrome stains and was Congo red negative. Immunofluorescence showed strong immunoglobulin M and kappa light chain staining around blood vessels but predominantly around myocytes. Ultrastructural examination revealed massive deposition of flocculent electron-dense material around myocytes and occasionally around blood vessels. PMID- 8191632 TI - Primitive cerebral tumor with rhabdoid features: a case of phenotypic rhabdoid tumor of the central nervous system. AB - The rhabdoid tumor (RT) was first described as an aggressive neoplasm of unknown histogenesis affecting the kidneys of infants and young children, but has since been reported in all ages and in many other primary sites, including the central nervous system. It has been shown, however, that the histologic and cytologic features of RT can be mimicked by many other tumors of known histogenesis. For this and other reasons it remains controversial whether cases of putative extrarenal RT represent the same histogenetic entity as RT of the kidney (RTK), another entity or entities, or merely a diverse collection of unrelated tumors sharing a common morphologic phenotype. The present paper describes a lethal primary cerebral tumor in a 26-month-old Hispanic boy that was composed predominantly of cells exhibiting the "classic" rhabdoid phenotype by light microscopy. Immunocytochemical and ultrastructural studies disclosed features of primitive neuroglial differentiation not seen in RTK. The findings in this case, as well as evidence from other studies, would seem to support the notion that primary RT of the brain may in fact constitute a morphologic and clinicopathologic entity. However, that entity likely represents a distinctive type of neuroglial neoplasm, more closely related to other primitive brain tumors than to RTK. PMID- 8191633 TI - Malignant meningioma of the scalp. AB - A nodule from the scalp of a 14-year-old boy was diagnosed by light and electron microscopy as a meningioma. There was no evidence of an intracranial lesion or involvement of the bone of the skull. The tumor was excised but recurred and metastasized to lung and chest wall. PMID- 8191634 TI - True histiocytic lymphoma with multiple skin nodules. AB - A 73-year-old white woman developed multiple cutaneous nodules that fluctuated in size and occasionally regressed. The tumor cells infiltrating the dermis were histiocytic by light microscopy, marker studies, and electron microscopy. Similar cells were present in a bone marrow biopsy specimen. A diagnosis of true histiocytic lymphoma was made. The case illustrates some of the problems that may arise in evaluation of clinical and pathologic findings in a patient with a proliferative disorder of histiocytes and demonstrates the contribution that electron microscopy can provide in establishing the diagnosis. PMID- 8191635 TI - Parachordoma. AB - Parachordoma is a soft tissue tumor that has a light microscopic appearance similar to that of chordoma, and the immunostaining properties of the two tumors are alike. The clinical findings and light microscopy of one case of parachordoma are presented together with ultrastructural observations on this tumor and parachordomas from five additional patients. PMID- 8191637 TI - Electron microscopy in the diagnosis of small round cell tumors of bone. AB - Small round cell tumors involving bone can present problems in differential diagnosis by light microscopy. In exploring the role of electron microscopy in this situation, seven small cell osteosarcomas and seven mesenchymal chondrosarcomas were examined by electron microscopy and compared with typical and atypical Ewing's sarcomas. There is much overlap in the ultrastructural features of these tumors, but electron microscopy is helpful to establish or confirm a diagnosis of typical Ewing's sarcoma and, if representative matrix is present, of small cell osteosarcoma. PMID- 8191636 TI - Extraskeletal myxoid chondrosarcoma with intracisternal microtubules. AB - A case of extraskeletal myxoid chondrosarcoma with intracisternal microtubules is presented. The microtubules were generally straight, parallel, closely packed, and evenly spaced, but they did not form geometric arrays. Aggregates of stromalike myxoid material were present in the cisternae and the adjacent cytoplasm. Microtubules were never found within the cytoplasm. A similar ultrastructural appearance was seen in 4 of 10 other examples of extraskeletal myxoid chondrosarcoma. PMID- 8191638 TI - Polyvinylpyrrolidone storage disease: a source of error in the diagnosis of signet ring cell gastric adenocarcinoma. AB - False-positive and false-negative diagnoses of cancer seldom occur during evaluation of gastric mucosal biopsy specimens obtained during flexible fiberoptic endoscopy of the stomach. When they do occur, false-negative diagnoses are usually the result of undersampling of the lesion, whereas false-positive diagnoses are the result of overinterpretation of benign histologic lesions. The diagnosis of diffuse signet ring cell adenocarcinoma is associated with both false-positive and false-negative diagnoses of cancer. The signet ring cell can be easily overlooked. Mucicarminophilic cells can be overinterpreted as diffuse signet ring cell adenocarcinoma. Polyvinylpyrrolidone is an unusual cause of this type of false-positive diagnosis of gastric adenocarcinoma. Judicious use of histochemical stains, immunohistochemistry, and electron microscopy plays a significant role in avoiding the false-positive diagnosis of diffuse signet ring cell adenocarcinoma. PMID- 8191639 TI - Filamentous inclusions in acinar cell carcinoma of the pancreas. AB - Acinar cell carcinoma of the pancreas exhibits a spectrum of histologic appearances. Some tumors can be readily identified by light microscopy, but others resemble endocrine/neuroendocrine neoplasms. Ultrastructurally, though large zymogen granules of acinar cells are usually distinctive, the zymogen granules of neoplastic acinar cells are sometimes abnormally small, overlapping in size with the granules of endocrine/neuroendocrine neoplasms. Six cases of acinar cell carcinoma, two with a typical histologic appearance and four that resembled endocrine/neuroendocrine tumors, were studied ultrastructurally. In addition to zymogen granules and abundant rough endoplasmic reticulum, all cases of acinar cell carcinoma exhibited pleomorphic, membrane bound inclusions that contained filaments. Similar inclusions were not identified in islet cell or carcinoid tumors, and several findings indicate that the inclusions represent deranged zymogen granules. In the ultrastructural study of a pancreatic neoplasm with granules, these inclusions may provide a clue for the diagnosis of acinar cell carcinoma. PMID- 8191640 TI - Fibrolamellar hepatic tumor with neurosecretory features and systemic deposition of AA amyloid. AB - A 28-year-old man presented with left cervical lymph node metastases and a 7-cm mass in the left lobe of the liver. Biopsy material from both sites revealed a fibrolamellar hepatocarcinoma (FLHC) with immunocytochemical and ultrastructural evidence of neurosecretory differentiation. The patient refused treatment. He died 6 years after the onset of symptoms with grade IV coma and bilateral bronchopneumonia. Postmortem examination disclosed persistent neoplastic disease in the liver and left lateral cervical lymph nodes as well as widespread deposition of AA amyloid in tumor stroma and in blood vessel walls of many tissues but mainly in the kidney, gastrointestinal tract, and heart. This appears to be the first report documenting the association of FLHC and amyloid deposition in the English literature. PMID- 8191641 TI - Meningioma with chordoid features. AB - Meningioma is a relatively common intracranial tumor, occurring most frequently in adults, and is capable of a wide variety of growth patterns. We describe a meningioma in a child that had a peculiar chordomalike appearance. The pathologic findings and distinction from chordoma are discussed. PMID- 8191642 TI - Pleural mesothelioma presenting as an axillary lymph node metastasis with anemone cell appearance. AB - A case of epithelial mesothelioma presenting as an axillary metastasis of unknown origin with anemone cells in a 33-year-old patient with pleural effusion is reported. The differential diagnosis included tumors that can be composed of cells with anemone shape (malignant lymphoma, leukemia, malignant melanoma, carcinoma, and mesothelioma). Tumor cells in the present case were positive for cytokeratins (Cam 5.2 and AE1/3) as well as vimentin antibodies and were consistently negative for carcinoembryonic antigen, Leu-M1, leukocyte common antigen, pan-B-cell and pan-T-cell antigen, Ber-H2, S-100 protein, HMB-45, and epithelial membrane antigen antibodies. On electron microscopy, the most remarkable features were the presence of abundant, long, slender microvilli, the lack of well-developed intercellular junctions, and only occasional tight junctions in some of the tumor cells. A pleural needle biopsy confirmed the pleural origin of the proliferation. The patient refused treatment and died 3 years after diagnosis. PMID- 8191643 TI - Ultrastructure of multiple sclerosis. AB - The electron microscopic features of 11 stereotaxic brain biopsies that demonstrated inflammatory primary demyelination consistent both morphologically and clinically with multiple sclerosis are addressed. Degeneration of inner oligodendroglial loops and uniform widening of inner myelin lamellae antedated complete destruction of myelin sheaths. Perivascular lymphocytes, macrophages, and plasma cells were in intimate contact with myelin sheaths. Astrocytes proliferated even away from demyelinated areas. In areas of chronic, established demyelination, oligodendrocyte numbers were greatly decreased, and fields of completely demyelinated axons were seen among astrocytic processes. Axonal injury, evidenced by the formation of axonal swellings, was apparent in maximally affected areas. At the edge of acute lesions with demyelinated axons, oligodendrocytes were preserved morphologically. Thinly myelinated axons indicative of central nervous system-type remyelination by oligodendrocytes were observed primarily at the edges of plaques. An unusual inclusion observed in presumed macrophages was "polelike" bodies 0.04- to 0.7-microns thick. Linearly arrayed, their presumably proteinaceous crystalline substance was moderately electron-dense. Many were membrane-bound and appeared to arise from the endoplasmic reticulum. We conclude that disturbance of the myelinating function of oligodendrocytes may be a critical event in the pathogenesis of multiple sclerosis. PMID- 8191644 TI - Electron microscopy what Izzits revisited: an ultrapath VI quiz. AB - Thirteen cases of various natures, selected from a collection shown and discussed at Ultrapath VI, are presented in quiz format for recognition or diagnosis. PMID- 8191645 TI - Ultrastructure of ependymoma. AB - Twenty-six ependymomas were studied by light and electron microscopy. By electron microscopy, the acellular zones around small vessels in light microscopic sections were seen to be composed of large numbers of closely packed, filament rich, cytoplasmic processes ringing small vessels. Lumina were consistently present but many of them were too small to be seen by light microscopy. The lumina contained slender, curving microvilli and variable numbers of cilia. Their bordering cells were connected by unusually long tight junctions. Electron microscopy can be useful to establish or confirm a diagnosis of ependymoma when the light microscopic appearance is atypical, or when the tumor arises in an unusual location. The clinical data on the 26 cases has been reviewed; follow-up information was available on 23 patients. PMID- 8191646 TI - Ependymoma with signet-ring cells. AB - Two patients presented with unusual primary brain tumors having abundant signet ring cells, for which electron microscopic study was necessary to establish the diagnosis of ependymoma. The light and electron microscopic features of these tumors are discussed, with brief comments on the differential diagnosis. PMID- 8191647 TI - Oligodendroglioma: the ultrastructural spectrum. PMID- 8191648 TI - Cushing's syndrome secondary to olfactory neuroblastoma. AB - A case of olfactory neuroblastoma in a 36-year-old woman who presented with florid Cushing's syndrome is reported. A nasal polyp, which proved to be an olfactory neuroblastoma, was resected. The procedure was followed by complete remission from the endocrinologic abnormalities. Postoperatively, the patient was well for 5 years until recurrence of both Cushing's syndrome and the nasal polyp was noted. Following combined transnasal-transcranial resection of the tumor, which extended into the anterior cranial fossa, the patient again experienced complete remission of Cushing's syndrome. Immunohistochemistry showed the tumor to be positive for neuron-specific enolase, synaptophysin, chromogranin, adrenocorticotropic hormone, beta-endorphin, and S-100 protein. Electron microscopy revealed neuritic processes containing microtubules and neurosecretory granules. This is the first reported case of Cushing's syndrome secondary to olfactory neuroblastoma. PMID- 8191649 TI - Pineal parenchymal tumors: an ultrastructural study with prognostic implications. AB - The pineal gland is host to a spectrum of neoplasms. Those considered to be derived from or differentiating toward pineal parenchymal cells are rare. Traditionally, pineal parenchymal tumors (PPTs) have been divided into 3 types: pineocytomas, pineoblastomas, and mixed or transitional tumors. Their characterization has been far from adequate and no firm diagnostic criteria, light microscopic or ultrastructural, have been established. In an attempt to provide more precise prognostic diagnostic criteria, we undertook a detailed ultrastructural analysis of 17 PPTs and found them to exhibit light microscopic and ultrastructural features strikingly similar to those of pineal parenchymal cells in varying stages of development, ranging from undifferentiated primitive neuroepithelial cells to mature pineal parenchymal cells. We endorse classification of PPTs based on a combination of their light microscopic and ultrastructural features. Accordingly, PPTs can be divided into three categories: 1) pinealoblastoma, 2) PPTs of intermediate or mixed differentiation, and 3) pineocytoma, a tumor of mature-appearing pineocytes. In keeping with this classification, our 3 pinealoblastomas behaved as highly malignant tumors. A correlation of morphology and prognosis was less evident between intermediate tumors and pineocytomas, perhaps the result of considerable variation in surgical and other therapies. Evidence of neurosensory differentiation, a feature noted to a varying extent in all but the pineoblastomas, included club-shaped "nerve endings" in 7 tumors, small numbers of dense core granules in 8, clear vesicles in 7, and structures suggestive of synapses in 4. With the exception of 3 undifferentiated PPTs or pinealoblastomas lacking nerve endings, all pineocytomas exhibited some combination of these markers of neuronal specialization. In that the ultrastructural features of these PPTs were more indicative of their aggressiveness than was their degree of light microscopic differentiation or grade, we consider electron microscopy a useful adjunct, not only in diagnosis but also in therapeutic decision-making and prognostication. PMID- 8191650 TI - Low molecular weight proteins and the kidney: physiologic and pathologic considerations. AB - Low molecular weight proteins are normally, essentially, entirely catabolized by the proximal tubules. Physiological and pathological aspects of the renal interactions of three of these proteins: light chains, B-2 microglobulin, and myoglobin share similarities, but are also unique in certain ways. In pathological conditions, some may produce glomerular, proximal or distal nephron and/or vascular alterations. PMID- 8191651 TI - beta 2-Microglobulin and the kidney: an overview. AB - beta 2 microglobulin is a potentially amyloidogenic low molecular weight protein. Increased serum levels are seen in renal diseases that decrease glomerular filtration and/or tubular reabsorption, dialysis patients, chronic inflammatory diseases, and certain malignancies. Various aspects of beta 2 microglobulin metabolism and its accumulation in the kidney are addressed. PMID- 8191652 TI - [Use of a sclera-fortifying collagen plasty with trophic component in the treatment of high progressive myopia]. AB - A modified scleroplastic operation is suggested, trophic collagenoplasty in which sclera-fortifying collagenoplasty is combined with subtenon implantation of a collagen infusion system. Using this system drugs stimulating trophic processes in the tissues of the posterior segment of the eyeball are infused within 7 to 9 days after surgery. Such operations were carried out in 42 eyes of 22 patients with high progressive myopia (8.0 to 27.0 diopters). The patients' ages varied from 30 to 57. Three months after surgery a manifest improvement of hydro- and hemodynamic parameters of the eyes, as well as of visual acuity with correction, of visual field, and of retinal light discriminating sensitivity were observed in the majority of patients (p < 0.05). The results of pre- and postoperative examinations demonstrate a high efficacy of such operations in patients with high progressive myopia combined with marked dystrophic changes in the tissues of the posterior segment of the eye. PMID- 8191653 TI - [Clinical aspects of strabismus with insufficiency of the superior oblique muscle]. AB - Clinical features of vertical strabismus with superior oblique muscle insufficiency were studied in 123 patients. A complex of clinical methods was used and clinical evaluation of these methods made. Various forms of strabismus with superior oblique muscle insufficiency were detected. Four degrees of superior oblique muscle weakness were distinguished corresponding to four degrees of inferior oblique muscle hyperfunction. PMID- 8191654 TI - [Local fibrinolytic activity of the lacrimal fluid in patients with arterial hypertension]. AB - Lacrimal fluid local fibrinolytic activity was measured in 101 patients with different variants of arterial hypertension. The studied parameter was found reduced in patients developing hypertensive retinopathy on the respective eye. A correlation was revealed between progress of hypertensive changes in the fundus oculi and reduction of lacrimal fluid local fibrinolytic activity. The results indicate that reduction of this parameter may be regarded as one of the prerequisites for the development of hypertensive retinopathy. PMID- 8191655 TI - [Clinical significance of the determination of several hemostatic parameters in the lacrimal fluid of patients with vascular diseases of the retina]. AB - Clinicolaboratory studies of 92 patients with vascular diseases of the retina (retinal vein thrombosis, central chorioretinal dystrophy, retinal hypertensive angiosclerosis) were carried out to assess hemorheologic parameters (platelet and red cell aggregation coefficients, blood viscosity). In parallel with this, lacrimal fluid was analyzed for hemostatic parameters, plasminogen and antithrombin III. A marked increase of plasminogen and antithrombin III levels was found in the lacrimal fluid of patients with retinal vein thrombosis, this increase correlating with pathologic shifts in the studied rheologic characteristics. Central chorioretinal dystrophy and retinal hypertensive angiosclerosis were associated with shifts in some rheologic characteristics. Hence, measurements of lacrimal fluid hemostatic parameters plasminogen and antithrombin III in patients with retinal vascular diseases help assess blood rheology. PMID- 8191656 TI - [Experimental validation of the efficacy of intraocular phonoelectrophoresis in eye diseases]. AB - Basing on clinical data (12 patients) and experimental results (42 rabbits), the authors defined the pharmacokinetic characteristics of drugs administered by endo ocular phonoelectrophoresis technique developed by them. Formation of the drugs' depot in the parabulbar space was demonstrated. Concentrations of the administered drugs in various segments of the eyeball were assessed. The values obtained during parabulbar injection of drugs were used as reference ones. PMID- 8191657 TI - [Local use of retabolil in the treatment of corneal pathology in experimental animals and clinical practice]. AB - Experiments with 30 rabbits revealed enhanced corneal epithelium regeneration under the effect of local (epibulbar and subconjunctival) retabolil therapy. Clinically 15 patients with epithelial-endothelial corneal dystrophy were treated with retabolil, the treatment being effective in all the cases when the initial visual acuity was at least 0.1 diopters. PMID- 8191658 TI - [Vodovozov's peripapillary reflex in peripapillary chorioretinal atrophy following papillary congestion]. AB - Peripapillary reflex first described by A. M. Vodovozov was diagnosed in 540 patients with optic disk edema of various origins. In seven patients a bright well-discernible reflex was found after postcongestive atrophy in the presence of peripapillary chorioretinal atrophy. Examination of the fundus oculi in transformed light has shown that peripapillary reflex in such cases develops at the site of difference of levels in the fundus oculi where a thinner area of the fundus round the disk in transforming and pigmented epithelium and choroid capillaries are absent, and an area situated more peripherally and characterized by normal thickness starts. The direction of the difference of levels in the retina in such cases is contrariwise to that in manifest congestive papilla. The studies have shown that Vodovozov's peripapillary reflex is diagnostically and prognostically important not only in the clinical picture of congestive papillae and secondary postcongestive atrophies, but even in cases when common and secondary optic nerve dystrophies are to be differentiated between. PMID- 8191659 TI - [Acanthamoeba keratitis (literature review and case report)]. AB - Clinical course, specificities in ophthalmologic and parasitologic diagnosis, drug and surgical treatment of keratitis caused by Acanthamoeba are described for the first time in Russian literature. Experience gained in two-year follow-up of a male patient with the condition who used soft contact lenses for a long time before he fell ill and the foreign literature data prompted the authors describe this disease. PMID- 8191660 TI - [Effects of low-intensity laser irradiation on visual fields of patients with glaucoma]. AB - Twenty-three patients (28 eyes) with open-angle glaucoma and controlled intraocular pressure were administered a course of He-Ne laser treatment. Irradiation parameters were as follows: wavelength 0.63 microns, light spot diameter 5 mm, energy 2 mWt, session duration 240 sec. A course consisted of 10 sessions. Seventeen eyes of the same patients were controls. Visual field was examined before the treatment and after it, immediately and in 3 to 3.5 months using Humphrey field analyzer and full field 120 points threshold related test. The treatment resulted in field deficit reduction by 10% and more in 21 (75%) of the 28 eyes. On an average, visual field deficit reduced by 22.4%. Three to 3.5 months after the treatment the mean value of visual field deficit was still lower than initially by 19.7%. No side effects were observed in any of the cases. In controls a trend to increase of field deficit developed within the same period, though the differences were statistically unreliable. The data indicate a positive effect of local low-energy laser exposure on visual field status of patients with primary open-angle glaucoma and controlled intraocular pressure. PMID- 8191661 TI - [Cystic eye and anophthalmos in a child with multiple congenital abnormalities]. AB - Cystic eye is a rare congenital disease representing a persistent primary ocular cyst cavity. A patient aged 2 is described with anophthalmia and cystic eye looking as an orbital tumor 25 x 35 mm in size. The infant suffered from delayed psychomotor and speech development. Ambilyacousia, thymomegaly, multiple hemangiomas of the skin, syndactyly, cryptorchidism, inguino-scrotal hernias were diagnosed. The totality of developmental abnormalities was a contraindication against anesthesia, therefore the proposed cystic eye enucleation with prosthesis implantation was not carried out. PMID- 8191662 TI - [Antioxidant therapy of primary glaucoma]. PMID- 8191663 TI - [Ascorbic acid in ophthalmology]. PMID- 8191664 TI - [Prevalence of primary glaucoma in Uzbekistan]. AB - The author analyzes the prevalence of glaucoma and medicosocial characteristics of patients suffering from this condition over the course of 5 years basing on the records of a glaucoma room in the town on Tashkent. The age, sex, education of the patients, social, and pathologic aspects of this problem are analyzed. Data on detection of glaucoma patients are presented. The author analyzes the stage of the process at the moment of diagnosis of open- or closed-angle glaucoma and emphasizes the low rate of surgical treatment. The incidence of the major concomitant diseases characteristic of patients with primary glaucoma is discussed. PMID- 8191665 TI - [Research-clinical trends in the study of injuries of the organ of vision]. AB - The author reviews stages in research and practical activities in the field of ocular injuries over the latest 50 years. Among the principal trends in practical work are rehabilitation of those who suffered in the Great Patriotic War, had occupational injuries to the eye (noteworthy is an increase in industrial and agricultural traumatism during the latest years), was injured during wars in Afghanistan or Vietnam when new types of weapons were used, had criminal traumas or injuries caused by extreme situations, catastrophes, or international conflicts. Approaches to search for new drugs and methods of surgical treatment of such patients are outlined. PMID- 8191666 TI - [Effects of the duration of cataract extraction and eyeglass wear in patients with aphakia on the development of changes in the macular area]. AB - Forty-eight patients with aphakia were examined to elucidate the effect of cataract extraction duration on subsequent development of Irwin-Hass syndrome. A total of 229 patients were examined 6 months and more after cataract extraction to find out whether sun light could induce development of dystrophic changes in the central retina in aphakia. The results indicate that operation duration of more than an hour increased the risk of subsequent development of Irwin-Hass syndrome. Aphakia patients wearing no eyeglasses or contact lenses or intraocular lenses may develop maculodystrophies, probably due to the injurious effect of sun rays on the retina. PMID- 8191667 TI - [Time factors in the performance of closed vitrectomy in traumatic hemophthalmos]. AB - The authors analyze the results of 447 vitrectomies in patients with traumatic hemophthalmia and its aftereffects, carried out in various periods after trauma. The best vision and the least number of complications (retinal detachment, hemophthalmia recurrence) were attained when vitrectomy was carried out in 1 to 3 months after the injury. An earlier vitrectomy involved a high risk of complications, and the vision results were poor; vitrectomy carried out later than 4 months after the injury was as ineffective because of irreversible posttraumatic changes in the retina. These results bring the authors to a conclusion that closed vitrectomy with optic purposes should be carried out in periods from 1 to 3 months after the injury. PMID- 8191668 TI - Ventricular arrhythmias in dogs undergoing splenectomy: a prospective study. AB - Fifty dogs undergoing splenectomy for splenic masses (n = 40), torsion of the splenic pedicle (n = 5), and immune-mediated disease (n = 5) were evaluated preoperatively and and postoperatively for ventricular arrhythmias and the relationship between ventricular arrhythmia splenic disease. The ability of 1 minute electrocardiograms recorded every 6 hours (ECGs/q6hr) to detect ventricular arrhythmia was compared with continuous 48-hour Holter monitoring. Based on continuous Holter monitoring, splenectomized dogs had a high incidence (22 of 50) of rapid ventricular tachycardia. The incidence of rapid ventricular tachycardia was significantly higher in dogs with ruptured splenic masses (16 of 23) than without rupture (1 of 17) (P < .001). When the results of ECG/q6hr were compared with the results of continuous Holter monitoring ECG/q6hr was normal in 29% (4 of 14) of dogs with rapid ventricular tachycardia at > 3,000 ventricular extrasystoles (VE)/hr; 50% (4 of 8) of dogs with rapid ventricular tachycardia at 1,000 to 3,000 VE/hr and 100% (6 of 6) of dogs with 10 to 300 VE/hr without rapid ventricular tachycardia. Although dogs undergoing splenectomy had a high incidence of ventricular arrhythmias, one-minute ECGs/q6h were unreliable for detection of ventricular arrhythmias even when high-frequency extrasystoles occurred. PMID- 8191669 TI - Sclerosing encapsulating peritonitis in four dogs and a cat. AB - Sclerosing encapsulating peritonitis (SEP) was diagnosed in four dogs and one cat. Clinical signs included vomiting, abdominal pain, palpable abdominal mass, and ascites. The abdominal fluid was red-tinged and contained large numbers of red blood cells, macrophages, mixed inflammatory cells, reactive mesothelial cells, and fibroblasts. At surgery, the typical appearance was of multiple surfaces covered with granulation tissue or fibrous tissue or both. Multiple adhesions were often present. Causes of SEP included steatitis, fiberglass ingestion, and bacterial infection. Treatment included administration of antibiotic, corticosteroid, and diuretic medications. The major long-term management problems were chronic weight loss, ascites, and progression of concurrent disease. PMID- 8191670 TI - Colopexy as a treatment for rectal prolapse in dogs and cats: a retrospective study of 14 cases. AB - Colopexy was evaluated as a treatment for recurrent rectal prolapse in eight dogs and six cats. Cases included in the study were from two institutions; the University of Pennsylvania School of Veterinary Medicine and the University of Tennessee College of Veterinary Medicine. Two different colopexy techniques were used: A simple suture technique was used in two cats and four dogs (University of Pennsylvania), and an incisional technique was used in four cats and four dogs (University of Tennessee). Rectal prolapse had not recurred in any of the 14 animals at the time of follow-up. Incisional dehiscence occurred in two animals and in one instance may have been related to the colopexy procedure. Infection at the colopexy site, secondary to suture penetration of the colonic lumen, is a potential complication of this procedure. Colopexy, using either surgical technique described here, was effective in preventing recurrent rectal prolapse. PMID- 8191671 TI - The effect of trans-stifle external skeletal fixation and hyaluronic acid therapy on articular cartilage in the dog. AB - Transarticular external skeletal (TES) fixators were applied unilaterally to the stifle joints of 10 young adult dogs. After 4 weeks, the fixators were removed from all dogs. Two dogs were not allowed a remobilization period, whereas 8 dogs were provided with 4 additional weeks of weight-bearing activity in a kennel run. Four dogs were given high-molecular weight hyaluronic acid by intra-articular injection weekly during the remobilization period. Clinical gait evaluations and range of motion were determined during the remobilization period. Articular cartilage samples from both stifle joints of all dogs were evaluated histologically and histochemically. No significant differences in gait scores or range of motion were noted between treated and untreated dogs. Articular cartilage proteoglycan content was reduced after 4 weeks of trans-stifle external skeletal fixation as determined by loss of alcian blue (AB) histochemical staining. Improved homogeneity of histochemical staining was observed after remobilization. However, remobilization was associated with histological damage to the surface and tangential layers of articular cartilage. Remobilization combined with hyaluronic acid (HA) therapy improved histochemical staining and reduced structural damage to articular cartilage when compared with remobilization alone. PMID- 8191672 TI - Sinography in the investigation of draining tracts in small animals: retrospective review of 25 cases. AB - The signalment, history, clinical signs, radiographic findings, and surgical findings of 25 consecutive animals that had sinography were reviewed to assess the contribution made by sinography to diagnosing and surgically managing draining tracts in small animals. There were 23 dogs and 2 cats; a variety of breeds and both sexes were represented (18 males, 7 females). Before referral the mean duration of clinical signs was 9.8 months (range, 0.5 to 33 months) and a mean of 2.0 surgical procedures (range, 1 to 5) had been performed. Sinuses occurred in a variety of locations, most commonly the neck (10), head (6), and paws (5). The most common cause was foreign body (15). Survey radiographs showed abnormalities in 21 of 26 (78%) instances, including soft-tissue swelling (11), chronic-appearing periosteal reaction on adjacent bones (5), possible foreign body (4), and gas in soft tissues (2). Sinography (or fistulography) enabled definite diagnosis of the cause of the sinus (or fistula) in 15 of 26 (58%) instances and demonstrated 13 of 15 foreign bodies (sensitivity 87%; specificity 100%). Tracts caused by an esophageal perforation and otitis media were also correctly shown by fistulography. In 11 animals, sinography indicated that the position or extent of the lesion was different to that expected on the basis of clinical signs and survey radiographs. PMID- 8191673 TI - Comparison of two indwelling central venous access catheters in dogs undergoing fractionated radiotherapy. AB - Twenty dogs with neoplasms requiring multiple radiation treatments received either percutaneous vascular access catheters (PVACs; Cook, Bloomington, IN) or subcutaneous vascular access ports (SVAPs; Vascular-Access-Ports, Norfolk Medical Products, Inc., Skokie, IL); 10 dogs were entered in each group. All catheters were implanted and removed aseptically and the catheter tips were cultured during implant removal. Complications with PVACs included mild incisional swelling and redness and accidental severance or rupture of the catheter. Complications with SVAPs included incisional or port swelling, bruising or redness, hematoma formation, and pain. Ports in 4 of these dogs could not be used for 1 to 3 days after surgery because of swelling and pain. Surgical wound complications, when pooled for comparison, occurred significantly more frequently with the SVAPs (P = .023). Wound complications associated with both catheters were self-limiting and resolved within 7 days. Bacterial cultures were positive in two PVACs and four SVAP tips, however, none of these dogs had clinical signs of infection or sepsis. Although both types of indwelling catheters were functional in a clinical setting, PVACs were preferred to SVAPs for dogs undergoing radiation therapy because of decreased time for implantation and fewer overall complications. PMID- 8191674 TI - The analgesic effects of administering fentanyl or medetomidine in the lumbosacral epidural space of cats. AB - The analgesic effects of fentanyl (4 micrograms/kg) and medetomidine (10 micrograms/kg) in 1 mL saline injected epidurally were measured in 15 cats. The response to an electrical cutaneous stimulus from a constant current generator was used as the index of analgesia. The stimulus was applied to a forelimb before epidural injection, and at 15, 30, 60, 90, 120, 180, 240, and 300 minutes post injection (PI). The hindlimb was tested 5 minutes later. One mL saline only was used to control for volume of injection and saline. Medetomidine significantly increased the pain threshold for the hindlimb at 20 to 245 minutes PI compared with the preinjection level. Fentanyl significantly increased the pain threshold at 20 minutes PI only compared with preinjection levels. Medetomidine significantly increased the pain threshold of the forelimb at 15 to 120 minutes PI compared with the preinjection levels. Fentanyl did not significantly increase the pain threshold of the forelimb. Administration of medetomidine produced emesis in 12 of 15 cats in an average of 6.4 minutes PI (range, 3 to 11 minutes) and mild sedation in all cats. Injection of fentanyl produced no visible side effects in any of the cats. PMID- 8191675 TI - The cardiopulmonary effects of placing fentanyl or medetomidine in the lumbosacral epidural space of isoflurane-anesthetized cats. AB - The cardiopulmonary effects of fentanyl (4 micrograms/kg) or medetomidine (10 micrograms/kg) in saline injected epidurally were measured for 2 hours in 15 isoflurane (2.4%)-anesthetized cats. One milliliter of saline without drug was used to control for saline and volume of injection. Baseline was taken as preinjection time 0. Medetomidine significantly increased (P < .05) mean arterial blood pressure (MAP) 5 to 20 minutes postinjection (PI) compared with baseline. MAP significantly decreased 30 to 120 minutes PI compared with baseline. Fentanyl significantly decreased MAP 5 to 120 minutes PI compared with baseline. Heart rate and respiratory rates significantly decreased in the medetomidine and fentanyl groups 5 to 120 minutes PI compared with baseline. Arterial pCO2 significantly increased while arterial pH significantly decreased 15 to 120 minutes PI in the fentanyl and medetomidine groups compared with baseline. Blood bicarbonate concentration significantly increased 90 to 120 minutes PI in the medetomidine group compared with baseline. PMID- 8191676 TI - Butorphanol does not reduce the minimum alveolar concentration of halothane in dogs. AB - This study evaluated the effect of butorphanol tartrate, a synthetic opioid agonist-antagonist, on halothane minimum alveolar concentration (MAC) in dogs. Baseline halothane MAC was determined in each of six dogs. Butorphanol was administered and halothane MAC was redetermined. Each dog received butorphanol at 0.2, 0.4, and 0.8 mg/kg intravenously at 1 week intervals. Heart rate and arterial blood pressure decreased after butorphanol administration, but returned to baseline by 50 minutes. There was little effect on respiratory parameters. A halothane-sparing effect was not noted with any butorphanol dose. PMID- 8191677 TI - Histological appearance of naturally occurring canine physeal fractures. AB - The Salter-Harris classification system is widely used to describe the anatomical appearance of and predict the prognosis for physeal fractures in canine clinical patients. Salter and Harris classified experimentally induced physeal fractures on radiographic and histological appearance, however, the good prognosis afforded Salter-Harris type I and II fractures in experimental animals has been questioned for the canine patient. Twelve naturally occurring physeal fractures from five traumatized dogs, who were euthanatized at the request of their owners, and one resected femoral head were examined histologically. Ten of the 13 physeal fractures disrupted the cells in the proliferative zone. The histological appearance of growth plate disruption in the injured animal correlates more closely with the clinical observations of growth retardation than the experimental observation of continued growth after fracture through the hypertrophic zone. The results of this study indicated that considerable damage to the physeal cartilage occurred during the traumatic incident in most of these clinical animal patients. PMID- 8191678 TI - Exposure and postoperative stability of three medial surgical approaches to the canine elbow. AB - Articular cartilage exposure and immediate postoperative stability provided by three medial surgical approaches in canine cadaver elbows were compared. The approaches evaluated were a desmotomy of the medial collateral ligament (DMCL) that included a tenotomy of the pronator teres muscle, a longitudinal myotomy of the flexor carpi radialis (MFCR), and an osteotomy of the medial epicondyle (OME). Nondestructive biomechanical testing was performed before the surgical approach and repeated after surgery. The stiffness at 13 degrees valgus deviation of the elbow and energy absorption up to 13 degrees valgus deviation of the elbow were determined from the preoperative and postoperative torque-rotation curves. The perimeters of the ulnar and humeral articular cartilage that were visualized through the approach were scored with a dental pick. Latex casts were made of articular surfaces of the elbow. The humeral and ulnar articular exposures were determined by computerized planimetric analysis of latex cast photocopies. The humeral cartilage exposure of the OME approach was significantly greater than either the MFCR or DMCL approaches. The DMCL approach provided a significantly greater humeral cartilage exposure than the MFCR approach. All three approaches provided statistically similar percentages of ulnar cartilage exposure. The stiffness and energy absorption of the OME and MFCR approaches were similar and significantly greater than the DMCL approach. The OME approach provided the best combination of exposure and immediate postoperative stability. PMID- 8191680 TI - [The estimation of recoverable medical losses in the therapeutic area]. PMID- 8191679 TI - Results of craniotomy for the treatment of cerebral meningioma in 42 cats. AB - Forty-two cats underwent craniotomy for removal of a meningioma between 1985 and 1991. Median duration of clinical signs before examination was 1.25 months. All cats had inappropriate demeanor: 48% were dull and 38% were lethargic. Neurological deficits included impaired vision in 93%, paresis in 83%, and seizures in 19%. Computed tomography (CT) showed solitary masses in 86% and multiple masses in 14%. Intraoperative complications included hemorrhage and difficulty excising deep or adherent masses. Anemia in 13 of 42 cats was the most common immediate postoperative complication. Ten of 42 cats had no improvement or a more severe neurological status after surgery. Eight of 42 cats died immediately after surgery; 6 of these were anemic. Of the cats that survived the immediate postoperative period, evaluation 10 to 14 days after surgery showed that 97% (33 of 34) were alert and 79% (27 of 34) had returned to normal behavior. Neurological deficits, except for vision impairment, had resolved in most cats. The duration of follow-up varied from 1.3 months to 55.1 months. Ten cats developed neurological abnormalities from 1 month to 44.2 months after surgery; of these, 6 had tumor recurrence or new growth confirmed by CT scan or necropsy. Overall survival was 71% at 6 months, 66% at 1 year, and 50% at 2 years. Age of cat and location of tumor did not significantly affect survival (P = .1034 and .1851, respectively). There were too few precise measurements of tumor size to make a valid statistical comparison of the effect of size on survival. Location or presence of multiple tumors did not affect final outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191681 TI - [The problems of teaching disaster medicine in training reserve officers at medical colleges]. PMID- 8191682 TI - [The preventive medical aspects in ensuring efficiency and safety in the operation of a fire-fighting and accident-rescue service]. AB - On the basis of national and foreign experience on liquidation of the consequences of natural calamities and catastrophies the article shows the necessity to introduce a course of medical training into the program of studies for the specialists of fire-fighting and rescue services of the Ministry for Internal Affairs of the Russian Federation (MIARF). This training will ensure these specialists with adequate skills of primary medical and predoctor care in disaster situations. The article contains basic items of the Program of medical training for the students of the St. Petersburg Higher Fire-Fighting Technical School of MIARF which was included into curriculum planning in 1992. PMID- 8191683 TI - [The organization of medical care in chemical accidents]. PMID- 8191684 TI - [The rehabilitation of minimally burned patients in hospitals for light casualties]. PMID- 8191685 TI - [Plastic operations in defects and deformities of the perioral area]. PMID- 8191686 TI - [The respiratory distress syndrome]. PMID- 8191687 TI - [The forensic psychiatric aspect of the clinical characteristics of psychogenic twilight states]. AB - Forensic psychiatry deals with two forms of active psychogenic twilight states: pathological affect and "short-circuit" reaction. These forms have the similar clinical manifestation which is subdivided into three stages: preparatory, explosive and concluding. These two forms differ only during the preparatory stage and with the psychogenic character of action, being practically the same during the proper psychic episode and at the final stage of psychosis. As a rule it is possible to distinguish two scenarios of psychogenic twilight state: illusory psychosensory and affective motoric. PMID- 8191688 TI - [The use of a sodium hypochlorite solution in surgical practice]. PMID- 8191689 TI - [The strategy and basic trends in optimizing immunoprophylaxis among the troops]. AB - On the basis of complex analysis of the present situation and problems of immunization in the Armed Forces the authors worked out the scientific substantiation of the principles and trends towards the improvement of immunoprophylaxis among servicemen. The article provides epidemiological evidence concerning the necessity to make a transition to a principle of a complex associated immunization, maintaining unchanged three basic regional schemes, as well as a 2-stage immunization with different approach to the various categories of servicemen, and a 4-5-valent protective vaccine complex for the first-term enlistees. The authors worked out a variant of a calendar and schedules for prophylactic vaccination of personnel in the Armed Forces of Russian Federation in peaceful time. PMID- 8191690 TI - [The status and trends in the improvement of specialized medical care]. AB - The article analyses the changes which have taken place during the last years in the functioning of the system of specialized medical care in the Armed Forces of Russian Federation. A new definition of this kind of medical care is given in this article, as well as its contents, components, and methods of its further improvement. The authors stress the positive results which were achieved by large multipurpose medical establishments with organic specialized medico-diagnostical units. Trends towards the further development of the system of specialized medical care were created taking into account the regional system of medical support of the Army and Navy. This article has a scientific and practical character and is interesting for the physicians and pharmacists of all specialties. PMID- 8191691 TI - [An epidemiological assessment of a temporary change in the schedules of prophylactic inoculations for Army and Navy personnel]. PMID- 8191692 TI - [The detectability of the hepatitis B surface antigen and antibodies to the hepatitis C virus in serviceman blood donors]. AB - Blood tests on HBsAg and anti-HCV were conducted in two groups of donors. The first group: 13677 servicemen, average age--20, constant place of residence- different regions of Russia. The second group: 1810 men (70%) and women (30%), average age--37, Moscow residence. In comparison with 1991 a reduction of positive HBsAg test results was marked in 1992 (by 1.6%) and in 1993 (by 1.8%), including 1.6 and 1.8% for combat units, and 2.2 and 3.9% for military construction units. In the authors' opinion such improvement of epidemiological HBV situation in the Armed Forces was caused by the fact that in autumn 1991 and in 1992 the drafting for the basic military service to the Russian Army was abolished in the regions of Middle Asia, Moldavia and Trans-Caucasus. The difference in anti-HCV positive results reduction between the first group (1.7%) and the second group (2.5%) can be explained by age factor, and by the more strict control over the selection of donors in the first group. PMID- 8191693 TI - [The problem of psychophysiological rehabilitation]. PMID- 8191694 TI - [The battle against smoking in different population groups]. AB - The article describes the measures against smoking in the former USSR. The authors stress an actual upgrade of antitobacco propaganda in many cities. Besides lectures and discussions different modern forms and methods of medical and educational influence are engaged: exhibition of children drawings on this theme, non-smoking days, antitobacco weeks, etc. A questioning of 5087 citizens of Moscow was carried out in order to study the spreading of smoking among the population. For example the number of smoking pupils of the 9-10th form is 22.7% among schoolboys, and 12.0% among schoolgirls. As for adult population: 64.5% of men and 21.6 of woman are smokers. The data which were obtained could be used for studying the efficiency of state program on prophylaxis and struggle against smoking. PMID- 8191695 TI - [The causes of persistent hearing loss in flight personnel]. PMID- 8191696 TI - [The importance of hospital dispensary ships in shaping a mobile system of treatment and rest for the population]. PMID- 8191697 TI - [The use of computer technology in the pharmacy system (a review of the literature)]. PMID- 8191698 TI - [The modernization of production models of shower disinfection units]. PMID- 8191699 TI - [Medical support for the troops of the Leningrad front in the Leningrad-Novgorod strategic offensive operation (on the 50th anniversary of the lifting of the blockade of Leningrad)]. PMID- 8191700 TI - [The Moscow Military Hospital in the War of 1812]. PMID- 8191701 TI - [The 75th anniversary of the Saratov Military Clinical Hospital]. PMID- 8191702 TI - [A meeting of veterans of the Battle for Leningrad]. PMID- 8191703 TI - [The blood serum biochemical indices as criteria for assessing the action on the body of industrial enzyme preparations]. AB - Workers of the enzyme industry showed changes of blood biochemistry advancing with the length of contacts with enzyme drugs as evidenced by inhibition of cholinesterase, activation of phosphatase and antitryptic blood serum activity. Increased content of blood histamine in these workers evidences sensibilizations to the enzymes, while simultaneous activation of monoaminoxidase should be considered as a compensatory reaction of the body. PMID- 8191705 TI - [The evaluation of the isoeffective distribution of the absorbed energy of fast neutrons in the therapeutic irradiation of patients]. PMID- 8191704 TI - [Changes in the concentration of cyanocobalamin, folates and ferritin in the blood serum of lymphoma patients undergoing chemo- and hormonotherapy]. PMID- 8191706 TI - [The comparative evaluation of the action of naniprus and perlinganit on the central and cerebral hemodynamics of patients with a myocardial infarct and pulmonary edema]. AB - A study is presented of 59 patients with macrofocal and transmural myocardial infarction and symptoms of pulmonary edema. It was found that in patients with myocardial infarction complicated by acute left ventricular failure, reduced reserves of autoregulation naniprus is the drug of choice for control of pulmonary edema, particularly, in case of hypokinetic type of cerebral hemodynamics. PMID- 8191707 TI - [Changes in the intracardiac hemodynamics of patients with essential hypertension during korinfar treatment]. AB - A study is presented of the structure and function of the heart in the diastole in 39 patients during corinfar treatment of essential hypertension. It was established that effective corinfar monotherapy of patients with moderate essential hypertension was associated with arteriolo- and venodilating effect of the drug with prevalence of the preloading effect. Changes of the intracardiac hemodynamics resulted in changes of the left ventricular systole phase structure, namely, its transformation in the direction of myocardial hypodynamia. PMID- 8191708 TI - [The etiotropic and pathogenetic treatment of patients with chronic gastritis and primary chronic gastroduodenitis]. AB - 120 patients with chronic gastritis and primary chronic gastroduodenitis were given a three-week course of etiopathogenetic treatment (antichelibacterial and immunocorrective drugs) that allowed to diminish the clinical, bacteriological and immune manifestations of the disease and achieve a complete cure in most patients. Patients with marked chelibacteriosis revealed greater refractoriness. The authors recommend prolonged courses of treatment with alternations of etiologically directed drugs. PMID- 8191709 TI - [The effect of parenterally administered nitrogenous preparations on the protein and lipid metabolic indices in normal and disordered liver function]. AB - It was established that liver failure is associated with significant disorders of the protein and lipid metabolism: marked increase of liver fat, increase of urea nitrogen, reduction of total protein. The blood shows a reduction of total lipids, cholesterol, phospholipids, triglycerides, total protein and albumin; the gammaglobulin level, rest nitrogen and urea nitrogen increase. Parenteral administration of nitrous drugs against the background of protein hunger does not deteriorate changes in the animal livers, furthers correction of the abnormal metabolism. PMID- 8191710 TI - [Traumas and foreign bodies of the large intestine]. AB - Results are reported of the treatment of 49 patients with trauma and foreign bodies of the colon. The authors evaluate the principles of diagnosis and treatment tactics depending on the volume of lesions in the colon and adjacent organs. The results of reconstructive-restorative operations after trauma of the colon are analyzed. PMID- 8191711 TI - [Herpes zoster in hematology patients]. AB - A clinical course of herpes zoster in hematological patients (chronic lympholeukosis, lymphogranulomatosis, acute leucosis, myeloma disease, chronic agranulocytosis) is presented. These patients exhibited a more severe course of herpes zoster that is caused by immunodeficiency state. It is judicious to treat the patients with reaferon. PMID- 8191712 TI - [The modern approach to the treatment of periodontitis]. AB - For the treatment of patients with chronic and exacerbated periodontitis trichopol and lincomycin were used as well-known effective antibacterial drugs in anaerobic non-clostridial infection. Zinc-eugenol paste was added. The results were favourable. PMID- 8191713 TI - [The clinico-morphological assessment of the changes in the interventricular heart septum in cardiomyopathy]. AB - A morphological study is presented of 120 hearts of those dying from different forms of cardiomyopathy. Postmortal coronarography, cardioventriculography, histological, histotopographic, volume-weight, and planimetric cardiometry, echocardiographic and pathomorphological methods were used. The interventricular septum showed a complicated construction pathognomonic for each form of cardiomyopathy. Echocardiographic and pathomorphological findings coincided completely in 43.3%, partially in 28.3% and were controversial in 23.3%. PMID- 8191714 TI - [The sulfhydryl groups and succinate dehydrogenase activity of the peripheral blood lymphocytes in diabetic patients]. AB - The peripheral blood lymphocytes of 72 patients with insulin-dependent diabetes mellitus showed a reduction of the SH groups and succinate dehydrogenase (SDG) activity, their grade depending on the severity of the pathological process. A dynamic study of the SH-groups and SDG activity of lymphocytes enable to evaluate the severity of disturbance of the oxidation-reduction processes in patients with diabetes mellitus. These data have also a prognostic significance. PMID- 8191715 TI - [The diagnosis and combined treatment of humeral fractures complicated by involvement of the radial nerve]. AB - Diaphysis fractures of the brachium are frequent and rather severe lesions resulting in losses of working capacity for a long term. Diaphysis fractures in association with lesions of the radial nerve of varying severity equal from 3.2 to 17.5%. The authors advocate a complex approach to the diagnosis and treatment of this pathology in 15 patients with an 1 to 5 years following. PMID- 8191716 TI - [The therapeutic properties of aloe]. AB - Data are reported on the use of aloes in research and folk medicine. Aloes is used in the form of dry juice of aloe leaves, fluid extract, juice, ointments. The author discusses indications and contraindications to the use of aloe. Recipes are given of mixtures with aloe which may be used in domestic conditions for increasing the defensive forces of the body during radiation lesions. PMID- 8191717 TI - [The use of an infusion of St.-John's-wort in the combined treatment of alcoholics with peptic ulcer and chronic gastritis]. AB - Hypericum herbal infusion was used in combination with rational psychotherapy of depressive manifestations in 57 outpatients with alcoholism and concomitant diseases of digestive organs. Duration of treatment--2 months (1 glass 4-5 times daily). It is concluded that this treatment in combination with rational psychotherapy proved effective. PMID- 8191718 TI - [A rare case of tracheobronchomegaly]. AB - The reported case confirms that tracheobronchomegaly may have a symptomless course. Exacerbation of process may be interpreted as "pneumonia". Only in the long course of the disease without positive clinico-roentgenological dynamics the correct diagnosis is established. PMID- 8191719 TI - [A case of progressive vibration-induced disease after discontinuing contact with vibration]. AB - A case is reported of advance of vibration disease in a woman with 23 year professional contact with vibration. 1.5 years after ceasing contact with vibration sources the vibration disease advanced and was complicated by vegeto sensory polyneuropathy of the upper extremities with trophic disorders and Raynaud's syndrome. PMID- 8191720 TI - [Local cryotherapy in insect stings]. PMID- 8191721 TI - [Drug species recommended in diseases of the cardiovascular system (notes for the physician)]. PMID- 8191722 TI - [The principles of planning and financing scientific research in public health in Ukraine]. PMID- 8191723 TI - [The pricing mechanism in the public health system]. PMID- 8191724 TI - [G. I. Bazilevich--well-known professor and clinician]. PMID- 8191725 TI - [Treatment principles in ventricular arrhythmias (a review of the literature)]. PMID- 8191726 TI - [The clinical picture and behavioral disorders in subjects working long term with xenobiotics (a review of the literature)]. AB - The effect is described of heterogeneous substances (xenobiotics) on the psychic function of the CNS. Data are reported of acute toxic encephalopathy developing under the effect of styrol, arsenic and manganese, chronic encephalopathy under the effect of such organic solvents as styrol and hydrogen sulphide, inorganic compounds of mercury, lead and manganese. PMID- 8191727 TI - [Microcrystalline arthropathies and hyperparathyroidism (a review of the literature)]. PMID- 8191728 TI - [The lymphoid system as the basis of body resistance and its role in the humoral regulation of reactivity and resistance by lymphopeptides]. AB - The priority function of the lymphoid system is considered not only as the basis for immunological reaction but also as a system which synthesizes different substances of peptide and nucleotide nature that equally determines the specific and unspecific resistance of the body to the action of antigenic and non antigenic factors of the environment. The lymphoid system role in fatigue, old age is stressed a leading mechanism in these processes on the basis of low molecular lymphopeptides synthetized by this system and providing the general resistance of the body and specific function of the morphofunctional systems. PMID- 8191729 TI - [The morphofunctional indices of the erythrocytic link in hemopoiesis in persons constantly working in an area of intensified radioecological control]. AB - A study of the peripheral blood indicates that persons constantly working in the zone of rigid radiation control showed a statistically valid reduction of the hemoglobin concentration, appearance of spinous and spheric erythrocyte forms, reduction of the mechanical resistance. Simultaneously 18% of males and 26% of females revealed moderate hypochromic anemia with a normal level of serum iron. The intensity of Fe-transferrin electron paramagnetic resonance was statistically reduced, that may be related to reduction of trivalent iron to bivalent and formation of a pool of free bivalent iron--a potent inductor of lipid peroxidation. Activation of oxidative processes in blood is confirmed by significant fluctuations of the blood ceruloplasmin level. PMID- 8191730 TI - [The morbidity in preschool children living on the territory of Rovno Province subjected to radioactive contamination as a result of the accident at the Chernobyl Atomic Electric Power Station]. AB - The morbidity was studied of 3000 preschool children born and inhabiting the territory of six Rovno Province districts belonging to the "Western trail" of the Chernobyl accident. It was found that the children born in 1986-1987 showed a 1.5 3 times increase of the morbidity as compared with the pre-accident period. PMID- 8191731 TI - [The structure of the morbidity and disability among miners who worked in the cleanup of the aftereffects of the accident at the Chernobyl Atomic Electric Power Station]. AB - The authors analyzed morbidity and invalidity in miners engaged in liquidation of Chernobyl disaster sequels depending on the duration of stay in increased radiation background, radiation dose, length of work in the mines. Among the nosological entities prevailed vegeto-vascular dystonia, thyroid and gastrointestinal pathology. PMID- 8191732 TI - [The effect of sulfonol, lead and nitrates on the structural-functional status of the liver in animals]. AB - It was established that combined peroral effect of sulfonol, lead and nitrates at maximum permissible level produces more pronounced changes in the liver of white rats than when these agents are used separately. Addition of nitrates to sulfonol and lead has a tendency to potentiate the reaction of the body. PMID- 8191733 TI - [The hygienic assessment of radio engineering devices radiating decimeter waves]. PMID- 8191734 TI - [The differential diagnosis of an autoimmune crisis and of a septic state in diffuse connective tissue diseases]. PMID- 8191735 TI - [The effect of plasmapheresis and antianginal therapy on lipid metabolism, eicosanoids and the thrombocytic link of hemostasis in patients with ischemic heart disease]. AB - A study of 126 patients with stenocardia receiving antianginal treatment was carried out with purpose of evaluating the effect of plasmapheresis on the clinical course of the disease, functional activity of thrombocytes, eicosanoids and lipid metabolism. It was shown that plasmapheresis improves the clinical condition of patients with ischemic heart disease, increases the tolerance to physical loads in patients with stenocardia. The mechanism of action of plasmapheresis is related to improvement of the lipid metabolism, system of eicosanoids, and thrombocytic link of hemostasis. PMID- 8191736 TI - [The characteristics of the psychological status of myocardial infarct patients and geomagnetic factors]. AB - An analysis is presented of myocardial infarction (MI) incidence during a 366-day period. Results were compared with prognostic and real unfavourable days by geomagnetic values (data of the Geophysical Institute in Gottingen (Germany)). There was no essential morbidity rise in the unfavourable days but a greater number of IM was noted during coincidence of prognostic and real unfavourable days. Among the patients persons with a definite psychological background prevailed. It is suggested that a greater sensitivity to geomagnetic factors is acquired during psychological and physical readaptation reflecting destabilization of the regulatory systems of the human body. PMID- 8191737 TI - [The gastrin and pepsinogen levels of patients with chronic atrophic gastritis and duodenal ulcer]. AB - The radioimmunological method was used to examine the content of blood plasma gastrin and pepsinogen in the blood plasma and bioptate of gastric mucosa in 22 patients with duodenal ulcer and 20 patients with chronic atrophic gastritis. Patients with atrophic antral gastritis show a reduction of the blood gastrin level while the pepsinogen level remained unchanged. In atrophic fundal gastritis the gastrin content rose while the pepsinogen level dropped. There was a clear increase of the pepsinogen level both in the blood plasma and bioptate of the gastric mucosa. The obtained data are of diagnostic significance in duodenal ulcer and chronic gastritis. PMID- 8191738 TI - [The cellular and humoral immunity status of patients with chronic enterocolitis]. AB - Results indicate that the course of chronic enterocolitis is accompanied by disorders of the immune system that depend on the severity and duration of the disease. To increase treatment efficacy of these patients it is necessary to institute differentiated immunocorrective therapy. PMID- 8191739 TI - [The reducing-diet therapy of chronic lesions of the gastroduodenal area]. AB - The author summarizes the experience of UDT in 140 patients with chronic gastritis (53) and gastroduodenitis (87) and 46 with duodenal ulcer. It was found that chronic diseases of the gastroduodenal zone were characterized by changes in the hematological and biochemical indices of the blood against the background of altered immune reactivity and that UDT favoured their normalization. PMID- 8191740 TI - [The validation of the possibility of obtaining antirabies donor plasma]. AB - The possibility was studied of obtaining of a highly-specific antirabies plasma from donor blood actively immunized with concentrated culture antirabies vaccine and optimal terms were determined for obtaining immunoreactive raw material for manufacturing of antirabies immunoglobulin. Technical aspects of manufacturing antirabies donor plasma are discussed. PMID- 8191741 TI - [The effect of Amanita phalloides poison on the ultrastructure of neutrophilic granulocytes]. AB - Changes of the ultrastructure of neutrophil granulocytes under the effect of Amanita phalloides was manifested by destabilization of cytoplasmic and organoid membranes, degranulation of the cytoplasm, appearance of areas of autolysis and lysed cells. The degree of destruction rose with increase of the dose and incubation time. PMID- 8191742 TI - [The seasonal dynamics of the indices of the oxidative-reductive processes in the erythrocytes of healthy subjects of different ages]. AB - A study is reported of the dynamics of the activity of enzymes markers of different metabolic ways--glycolysis, pentosophosphate cycle, gluconeogenesis--in erythrocytes of 157 practically healthy subjects in two age groups: from 20 to 35 years and from 35 to 60 years. It was shown that seasonal biorhythms of the above values that were definite in the young changed with age. These findings suggest the necessity of a chronobiological approach to research and clinico-laboratory investigations. PMID- 8191743 TI - [The effect of therapeutic plasmapheresis on the hemostatic system of patients with chronic glomerulonephritis and the nephrotic syndrome]. AB - Plasmapheresis was carried out by the continuous method in 10 patients with active forms of glomerulonephritis with the nephrotic syndrome and was found to positively affect hemostasis (reduction of hyperfibrinogenemia, thrombinemia, enhancement of fibrinolysis). Antiaggregants completely controlled negative effect of plasmapheresis on the thrombocyte status. The positive effect was paralleled by clinical improvement. PMID- 8191744 TI - [Phytotherapy in arterial hypotension (notes for the physician)]. PMID- 8191745 TI - [The processes of lipid peroxidation and renal functions in nephrogenic hypertension]. AB - Alpha-tocopherol acetate produced a positive effect on the renal function in patients with nephrogenous hypertension due to replenishment of endogenous antioxidants and its regulatory effect on lipid peroxidation. As a result there occurs a reduction of highly-toxic products of lipid peroxidation, improvement of renal microcirculation, reduction of ischemic disorders in the organs of the body. PMID- 8191746 TI - [The clinical picture, diagnosis and treatment of thoracalgias]. AB - The clinical picture of 260 patients with thoracalgia was characterized by chest pain, thoracic spine pain, subcostal and epigastric pain. In several patients treatment (traditional) failed. Different diseases of the digestive organs were found: chronic cholecystitis, biliary dyskinesia, gastric and duodenal ulcers which significantly contributed to the painful syndrome. Cooperation of the neurologist, gastroenterologist and surgeon favoured adequate rehabilitation of this category of patients. PMID- 8191747 TI - [The characteristics of computed study data on the brain in viral meningoencephalitis]. AB - An analysis is presented of CT examination of the brain in viral meningoencephalitis in 113 patients with viral encephalitis. Pathological changes in the acute period were found in 65.4% of patients more frequently in the CSF system, rarer in the brain tissue (in herpetic encephalitis). During the early convalescence period 75% of patients showed dilated ventricles and external CSF spaces. The importance of CT examination in this kind of pathology is emphasized. PMID- 8191748 TI - [Systemic arterial hypertension in rheumatic heart defects (a lecture)]. PMID- 8191749 TI - [The effect of pharmacological and heliogeophysical factors on the pathomorphosis of hyperthymic states]. AB - A clinico-statistical analysis of 1006 case histories of in-patients with affective psychoses treated in the Poltava Regional Mental Hospital from 1957 through 1978 revealed that maniacal conditions underwent significant changes during 22 years. This occurred against the background of more intensive use of psychotropic agents and changing heliogeophysical factors. PMID- 8191750 TI - [The significance of a natural inhibitory factor in the pathogenesis of disseminated sclerosis]. AB - Results indicate that during exacerbation patients with multiple sclerosis showed marked T-lymphopenia, decrease of histamine-sensitive RFC while active RFC exhibited varied changes of their content; increase of the circulating immune complexes, absence or low NIF level. The effect of corticosteroid therapy on the NIF dynamics was evaluated and its level was found to be increased due to hormone treatment. Prednisolone furthers T-cell immunodeficiency and also reduces the intensity of autoimmune reactions in multiple sclerosis. NIF may be used as a prognostic criterion for the evaluation of completeness and duration of the remission. Prolonged functioning of NIF leads to suppression of the patient's immune reactivity requiring immunocorrection. PMID- 8191751 TI - [The diagnostic importance of antibodies to the cell wall peptidoglycan of Staphylococcus in the blood serum of children with a staphylococcal infection]. AB - High titers of antibodies to peptidoglycan of staphylococcus aureus were found in children with purulent-inflammatory diseases of staphylococcal etiology. This may be used for the diagnosis of staphylococcal infection. PMID- 8191752 TI - [The clinico-pathogenetic aspects of severe and protracted forms of viral hepatitis B]. AB - The authors studied specific viral sensibilization and autoimmune processes in the pathogenesis of acute and protracted forms of viral hepatitis B. Combination of pronounced indices of virus-specific sensibilization and autosensibilization to the liver tissue without any tendency to reduction of the disease in its dynamics evidences the formation of severe and protracted course of viral hepatitis B. PMID- 8191753 TI - Antinuclear antibodies and breast implants. AB - Anecdotal reports have linked silicone breast implants to autoimmune diseases, with scleroderma being mentioned most often. In view of other environmental influences--such as silica mining and the toxic oil syndrome--thought to predispose to scleroderma, more systematic immunologic information on women with silicone implants is needed to assess any possible relation to autoimmunity. A cross-sectional survey was carried out with 150 women, of whom 131 had implants. Group 0 consisted of 19 volunteer women without breast implants who felt healthy, group I was 38 volunteer women with breast implants who felt healthy, group II was 82 women with implants who had various symptoms, and group III was 11 women with implants who had autoimmune disease. Scleroderma was overrepresented in group III (6 of 11). Antinuclear antibodies were determined on Hep-2 cells, using serum dilutions of 1:16, 1:64, and 1:256. A positive test was indicated by 1+ or more fluorescence at 1:256. Antinuclear antibody tests were positive in 0% of group 0, 18% of group I (P < .05 versus group 0), 26% of group II, and 64% of group III. There was no correlation between antinuclear antibody positivity and type of implant, indication for implantation, time since first implantation, total number of implants, and report of implant leak or rupture. Women with breast implants may be at risk for the development of antinuclear antibodies. Proof of such an association will require large-scale prospective studies and epidemiologic analyses. PMID- 8191754 TI - Is needle-directed breast biopsy overused? AB - We undertook this study of needle-localized breast biopsy--a frequently done surgical procedure--to examine current practice patterns and to determine if the technique is overused in any group of patients. From a retrospective review of medical records of all patients who had needle-localized breast biopsy at a teaching hospital between June 1, 1988, and October 31, 1990, we found that a total of 125 were done: 24 biopsy specimens showed malignancy (19%). Mammographic indications for biopsy were microcalcification (n = 62, or 50%), mass or density (n = 60, or 48%) and mass and calcifications (n = 3, or 2%). Indications for biopsy in patients with cancer were microcalcification (14 patients) and mass or density (10 patients). The incidence of malignancy increased with age. In patients younger than 40 years, no biopsy showed malignancy. Only 2 of 30 biopsies done in patients younger than 50 showed cancer (7%). Breast cancer was most frequently discovered in patients in the seventh and eighth decades of life, and this group accounted for 75% of "positive" biopsies. Needle-localized breast biopsy is a useful technique in the early diagnosis of breast cancer. Although indications for the procedure should remain liberal, in women younger than 50, the percentage of biopsies that reveal malignancy is low. PMID- 8191755 TI - Patients' understanding and use of advance directives. AB - The Patient Self-Determination Act was implemented in December 1991. Before and after its implementation, we used a structured interview of 302 randomly selected patients to determine their awareness, understanding, and use of advance directives. Implementation of the Act did not have a major effect on these. Although more than 90% of patients were aware of the living will, only about a third selected the correct definition or the correct circumstances in which it applied, and less than 20% of patients had completed one. About a third of patients were aware of a Durable Power of Attorney for Health Care and chose the correct definition, and about half identified the correct circumstances in which it applies; less than 10% had completed such a document. Surprisingly, patients who said they had completed advance directives did not demonstrate better understanding of these documents. Our results indicate that many patients, including some who have completed advance directives, do not fully understand them. It may be unwise to regard these documents as carefully considered, compelling statements of patients' preferences. Appropriate responses to our findings include increased public education, revising state statutes to bring them into congruence with public perception, and expanding the dialogue between physicians and patients. PMID- 8191756 TI - Magnetic resonance imaging and measurement of blood flow. AB - Blood flow can be shown as a negative image with magnetic resonance spin-echo techniques or as a positive image with gradient-echo techniques. Phase contrast refers to techniques where structures can be seen because of flow-induced phase shifts. These techniques can show the presence (slow flow) and also the direction of flow. Gradient-echo techniques--including phase-contrast versions--can be used with cardiac synchronization to obtain multiple images during the cardiac cycle. These images can be viewed in a movie or cine format to provide dynamic information about blood flow. Blood flow can be measured by using contrast media in boluses or even more elegantly with phase-contrast methods. Clinical applications of flow measurements are growing rapidly. Phase-contrast or gradient echo techniques can be used to create magnetic resonance angiography, which was first used to study the carotid bifurcation and intracranial circulation and is now being used throughout the body. PMID- 8191757 TI - Depression followed by dementia and disordered movement. Clinicopathologic correlation. PMID- 8191758 TI - Thyroid function tests--the next generation. AB - The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in internal medicine. 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 internal medicine 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 Internal Medicine of the California Medical Association, and the summaries were prepared under its direction. PMID- 8191759 TI - Watchful waiting for localized prostate cancer. PMID- 8191760 TI - Diabetes mellitus--new hope for an old disease. PMID- 8191761 TI - Pharmacologic stress echocardiography. PMID- 8191762 TI - Tuberculosis and human immunodeficiency virus disease. PMID- 8191763 TI - Hormonal therapy for metastatic prostate cancer. PMID- 8191764 TI - Current diagnosis and treatment of Helicobacter pylori. PMID- 8191765 TI - Heparin therapy for venous thromboembolism. PMID- 8191766 TI - Acute histoplasmosis acquired in Mexico. PMID- 8191767 TI - Factitious simulation of systemic lupus erythematosus. PMID- 8191768 TI - Black widow spider (Latrodectus mactans) bite during pregnancy. PMID- 8191769 TI - A brief history of health care quality assessment and improvement in the United States. AB - We review the history and current efforts to assess and improve health care in the United States. This process has involved a host of government agencies and commissions, professional organizations, insurance underwriters, corporations, and more recently, market forces. Traditional approaches to quality control have stressed case-by-case analysis and identifying outliers. Newer approaches include creating practice guidelines and profiles of hospitals and physicians. The joint goals of quality improvement and cost control can best be realized if institutions and practitioners embrace these new approaches and use them to enhance their performances. PMID- 8191771 TI - Health care. Transformation of systems and soul? PMID- 8191770 TI - Will managed care alter the art and soul of medicine? PMID- 8191772 TI - Ebb and flow of the circulation. PMID- 8191773 TI - Needle biopsy of probably benign nonpalpable breast lesions. PMID- 8191774 TI - Treating Hansen's disease in developing countries. PMID- 8191775 TI - Specialty care needs of a medically indigent adult population. PMID- 8191776 TI - Improving response to domestic violence. PMID- 8191777 TI - Food for thought. PMID- 8191778 TI - DNA testing and genetic counseling: truth or consequences. AB - Advances in medical genetics are providing a major clinical challenge to practitioners seeing patients concerned about their risk of developing either inherited disease or susceptibility to acquired disease. Popular information can easily exceed our professional ability to provide services to well-read patients who want answers with scientific certainty. The challenge also involves ethical questions regarding confidentiality and the way that results are disclosed. More often than not, the test itself becomes the focus of psychosocial expectations for the future and lifestyle of the patient and family. The behavioral consequences of disclosure of test results need to be anticipated by the caregiver to avoid adverse psychological outcomes. PMID- 8191779 TI - Outcomes of resuscitative efforts at Wild Rose Hospital. PMID- 8191780 TI - LEEP: early experience with a new approach to cervical lesions. AB - The loop electrosurgical excision procedure (LEEP) is a new diagnostic and therapeutic approach for the management of cervical lesions found during the evaluation of abnormal findings from Papanicolaou smears. The procedure may be an alternative to laser therapy, cold knife conization, cryotherapy or hot cautery. The first 235 consecutive LEEPs performed at the Gundersen Clinic were reviewed 6 months after the last procedure was done. Twelve of 187 patients with follow up Papanicolaou smears and clinic visits had persistent disease. Nine of 187 patients had a repeat LEEP. LEEP was found to be a highly effective means for diagnosis and treatment as 98% of the patients were free of evidence of recurrent cervical lesions 6 months after the initial LEEP. PMID- 8191781 TI - Asthma hospitalizations in Wisconsin: public health implications. PMID- 8191782 TI - The use of practice guidelines in Wisconsin for liability protection. AB - It seems many physicians and other health care professionals are reluctant to advocate that the use of clinical guidelines be expanded because of negative experiences with managed care entities that have based their practice guidelines on economic considerations. Those experiences have led to the erroneous belief by some that all guidelines are minimal or substandard. The trend is clear, however, that clinical practice guidelines will be increasingly important not only in courts but also in the management of health care. They are here to stay and they provide the medical profession with an opportunity now more than ever to decide its own destiny in medical malpractice litigation without the need for new legislation in Wisconsin. Accordingly, physicians should become pro-active at medical staff departmental meetings, in local and national professional associations, and, if necessary, in the political arena to encourage the adoption of valid guidelines--those that meet acceptable medical standards. In this way the risk that practice guideline use will become both the maximum and minimum standard of care will remain only a theory. While the decision to use clinical practice guidelines is solely up to a physician, he or she should be aware of a guideline's recommendations for any given patient situation. Ideal practice can still be followed by bad outcomes that prompt patients to claim negligence. By choosing a valid guideline and making a reasonable attempt to follow that guideline, a physician has maximized his or her opportunity for both preventing and prevailing in litigation. If, however, a guideline exists and it is unintentionally ignored, liability is more likely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191783 TI - New guidelines on HIV, nicotine released. PMID- 8191784 TI - Expression of soluble forms of rubella virus glycoproteins in mammalian cells. AB - Rubella virus (RV) virions contain two envelope glycoproteins, E1 and E2. Removal of hydrophobic regions in their carboxyl termini by genetic engineering caused them to be secreted rather than maintained in cell membranes of transfected COS cells. Truncated E2 was secreted in the absence of E1, whereas E1 lacking its transmembrane domain required coexpression of E2 for export from the cell. Secreted E2 was found to contain both O-linked and N-linked complex glycans, whereas secreted E1 retained virus neutralization and hemagglutination epitopes, suggesting the possibility of using soluble RV antigens as subunit vaccines and for serodiagnostic purposes. Stable Chinese hamster ovary cell lines secreting RV E1 were constructed for large scale preparation of recombinant E1. PMID- 8191785 TI - Change in phenotype of tick-borne encephalitis virus following passage in Ixodes ricinus ticks and associated amino acid substitution in the envelope protein. AB - Serial passage of an uncloned tick-borne encephalitis virus (strain 4387 isolated from the liver and lungs of a bank vole) in Ixodes ricinus ticks, was accompanied by gradual reduction in virulence of the virus, as indicated by transmission of virus by infected ticks feeding on laboratory mice. After the 7th serial passage in ticks (strain 4387/7), 95% of mice survived the bite of infected ticks. The surviving infected mice showed either no or only low viraemia although virus could be isolated from the brains of some mice 14 and 30 days after commencement of tick feeding, implying that the tick passaged virus might have established a persistent infection in the mice. Tests for haemagglutinating capacity were positive with TBE strain 4387 but strain 4387/7 exhibited no haemagglutinating activity over a wide pH range, suggesting that phenotypic changes, resulting from selection, had affected the site on the viral envelope protein that binds red blood cell receptors. Sequencing of the envelope protein gene of the virulent TBE strain 4387 showed 3 amino acid codon differences from western European TBE virus strain Neudorfl, which is also virulent for mice. The attenuated virus 4387/7, had an amino acid substitution that was different from 4387 and Neudorfl TBE virus (amino acid 84, E to K) and a second substitution different from 4387 but identical to Neudorfl virus (amino acid 319, I to T). Thus, the phenotypic change from virulence to attenuation was associated with a single amino acid codon change in the viral envelope gene of TBE virus. It is recognised, however, that amino acid substitutions in other parts of the viral genome have not been ruled out. PMID- 8191786 TI - Comparison of sequences of the H, F, and N coding genes of measles virus vaccine strains. AB - Many live-attenuated vaccines for measles virus have been developed using either the prototype Edmonston strain or other locally isolated measles strains. The attenuation methods used to develop these vaccines have differed in the type(s) of cell line(s) used, number of passages, and temperatures of incubation. To assess the extent of genetic diversity within vaccine strains and to determine the extent to which the varied passage histories may have affected the viruses, we conducted sequence analyses of the fusion, hemagglutinin, nucleoprotein, and matrix genes of Edmonston-derived and non-Edmonston-derived strains. Despite the diverse geographic origins of the vaccine viruses and the different attenuation methods used, there was remarkable sequence similarity among all strains examined. The sequences of all of the vaccine strains were very similar to the sequences of a low-passage seed of the original Edmonston strain. The most divergent sequences were from two of the non-Edmonston-derived vaccines: CAM-70, a vaccine developed from a Japanese wild-type virus, and S-191, which was developed in China. PMID- 8191787 TI - Spodoptera frugiperda Sf-9 cells nuclear factor binds to a specific sequence on the baculovirus polyhedrin promoter. AB - The promoter of the baculovirus polyhedrin gene is used for the heterologous expression of proteins in the baculovirus expression system. The polyhedrin gene of baculovirus is a very late gene that is hyper-expressed 18-24 h post-infection (P.I). We analyzed the DNA-binding activity of the polyhedrin promoter using gel mobility shift analysis, DNaseI footprint analysis and UV cross-linking experiments. Specific DNA-binding activity was found in uninfected cells. Specific binding activity was also found in cells during the early stage of viral infection and it decreased 18-24 h P.I. The DNA-binding activity localized to positions -72 to -86 on the polyhedrin promoter relative to the initial ATG. The molecular mass of the protein interacting with the DNA was in the range of 200 kDa. The data implies the presence of a host-encoded DNA-binding protein that acts as a negative regulator and is involved in the delayed expression of polyhedrin. In an initial attempt to test this hypothesis, transient cotransfection assays were performed in infected cells. These experiments were designed to assess the in vivo competition of proteins that interact with the polyhedrin promoter. The results support the concept of negative regulation. Thus it is possible that baculovirus utilizes an insect cell-derived nuclear factor to control the differential expression of late versus very late genes. A model that can account for our observations is discussed. PMID- 8191788 TI - Development of a nested-PCR test based on sequence analysis of epizootic hemorrhagic disease viruses non-structural protein 1 (NS1). AB - Two orbiviruses, epizootic hemorrhagic disease (EHD) and bluetongue (BTV) viruses, cause disease in domestic and wild ruminant species. The gene that encodes non-structural protein 1 (NS1) of EHD virus, serotype 1, was sequenced and compared to EHD and BTV NS1 sequences. The NS1 gene was found to be more conserved than the VP3 gene, and was selected as a target for polymerase chain reaction (PCR) amplification. The NS1 genes of several BTV viruses and another orbivirus, African horse sickness (AHS), were compared to the EHD NS1 genes. This information was used to develop a capture nested-PCR for detection and differentiation of EHD from BTV viral RNA. PMID- 8191789 TI - Construction of SV40 deletion mutants and delimitation of the binding domain for heat shock protein to the amino terminus of large T-antigen. AB - SV40 large T-antigen (T-ag) mutants were generated using a cassette mutagenesis strategy and naturally occurring restriction sites. T-ag mutant constructs included internal in-frame deletions, frame-shift deletions that resulted in amino-terminal fragments, and internal initiation mutants that produced carboxy terminal fragments; no foreign amino acids were introduced. The deletion mutants were stably expressed in BALB/c 3T3E cells and were analyzed for ability to bind heat shock cognate protein 70 using an ATP release assay of T-ag immunoprecipitates. Complex formation between heat shock protein and T-ag was independent of p53 involvement. The heat shock protein binding domain was narrowed to the amino-terminal 97 amino acids of T-ag, with the first 29 residues influencing the interaction. The amino-terminal domain of T-ag is important in both viral replication and cell transformation. We propose that the functional interactions of this highly interactive region of T-ag may be modulated by heat shock cognate protein 70. PMID- 8191790 TI - Complete nucleotide sequence of the RNA 3 from subgroup II of cucumber mosaic virus (CMV) strain: Trk7. AB - The complete nucleotide sequence (2209 nucleotides) of the RNA 3 of the cucumber mosaic virus strain Trk7 was determined. Trk7-CMV possesses two open reading frames which encode the 3a protein (279 amino acids) and the coat protein (218 amino acids). Sequence analysis proved the earlier biological and serological classification of the RNA 3 molecule of Trk7-CMV in subgroup II. A high degree of homology was found in the strains Q and Kin of CMV, while the average similarity between the two different subgroups is much lower. PMID- 8191791 TI - The effects of solar ultraviolet radiation on the eye. PMID- 8191792 TI - European action for victims of medical accidents. PMID- 8191793 TI - [Are self-reported diseases reliable and plausible? Problems in the estimation of the prevalence of heart infarct using questionnaires data from the National Health Survey]. AB - With the data of the German National Health Survey the question is discussed, if self-reports on diseases, gained in a survey, are useful for estimating prevalences within the German population. Self-reports on myocardial infarction serve as an example for examining the reliability and plausibility of such data. The prevalence rate for myocardial infarction in this survey is compared with prevalence rates of other data sources as the MONICA-register and surveys. Because these other data sources have some problems and deficits according to their validity too, the value of self-reports on diseases from the National Health Survey is seen positively for establishing a health reporting system. PMID- 8191794 TI - [Drug treatment of patients with heart infarcts before and after the acute stage: results of the Heart Infarct Registry Augsburg]. AB - To assess the changes in medications prescribed before and after acute myocardial infarction (AMI), all surviving patients aged 25-74 years registered from 1985 1988 in the Coronary Event Register Augsburg were evaluated by sex, medical history, and drug use before and after the event. For the 1546 hospitalized patients (1181 men, 365 women) utilization of all drug groups is higher for patients with reinfarction than for patients with first-ever AMI. Before AMI, but not on hospital discharge, women received significantly more medications than men and were more frequently treated with diuretics (30%; men 18%), antihypertensive drugs (15%, men 8%) and cardiac glycosides (20%; men 14%). The most frequently used drug groups are nitrates (before AMI: 30%; after AMI: 80%) and calcium antagonists (before AMI: 26%; after AMI 61%). The four years show a significant increase in patients with reinfarction who were treated with platelet aggregation inhibitors (1985: 9%; 1988: 32%), as well as an increase in AMI patients released from hospital with this medication (1985: 38%; 1988: 64%). A concomitant significant decrease in reinfarction rates for men is found in the course of the four years under study. The results indicate a rapid assimilation of the results of clinical trials in practice down to the substance level. PMID- 8191795 TI - [Are medical students sufficiently vaccinated? Results of a serological survey and of vaccine coverage]. AB - A total of 143 medical students participated in a serological and immunization coverage survey in Geneva. Between 29 and 54% had not received the 6 injections recommended in Switzerland against tetanus, diphtheria and poliomyelitis. The vaccination rates remain low against measles (57%), rubella (46%) and mumps (11%). Satisfactory levels of antibodies against measles were detected in all students. Between 4 and 6% did not have antibodies against mumps, varicella and rubella. Only 5.4% of Swiss medical students had antibodies against hepatitis A. HBc antibodies were present in 4% of the students. Medical students are at risk of contracting and transmitting vaccine preventable diseases. Swiss medical schools should play a leading role in the development of screening programs encouraging immunization of students entering university. PMID- 8191796 TI - [Study on endocytosis and nuclear accumulation of epidermal growth factor (EGF) in normal C3H mouse fibroblast cells C3H10 T1/2C18 and 3H-TdR transformed counterpart cells]. AB - In this study, we investigated endocytosis and nuclear accumulation of epidermal growth factor (EGF) in normal C3H mouse embryo fibroblast cells C3H10 T1/2 C18 (designated NC3H10) and 3H-TdR transformed counterpart cells (designated TC3H10). The results revealed that 125I-labelled EGF bound to the receptor on the cell surface of the two cell lines was subsequently endocytosed and translocated from the cell membrane to the nucleus, where it progressively accumulated. NC3H10 showed more EGF accumulation in nucleus than TC3H10 (p < 0.05). SDS polyacrylamide gel electrophoresis revealed that the endocytosed 125I-EGF associated with the nucleus was intact, with negligible breakdown products present. The nuclear accumulation of intact EGF in the mentioned cell lines exposed to ammonium chloride (a lysosomal inhibitor) was higher than the control (p < 0.05). These results suggested that receptor-mediated endocytosis and nuclear accumulation of EGF may play an important role in mediation some of the action of EGF. PMID- 8191797 TI - [Study on the relationship between two second-messenger pathways on the regulation of proliferation and differentiation in MGc 80-3 cells]. AB - By using an inducer of differentiation (HMBA) and blockers of signal pathways, the relationship between two second-messenger pathways (DG-PKC, cAMP-PKA) in inducer-mediated MGc80-3 cell differentiation was studied. Cells were treated with HMBA for 24 h, levels of DG decreased by 64.7%, activity of PKC decreased by 28.7%, while levels of cAMP and rate of it's protein binding increased by 62% and 32.6% respectively (after treated for 48 h, the result was more remarkable). PKA R II distributed in nuclei. H7 (PKC inhibitor) was used to substitute for HMBA to block the DG-PKC pathway. After treatment for 24 h, the levels of DG and activity of PCK both decreased, while the levels of cAMP increased 1.04 times. On the contrary, PKA inhibitor was added while HMBA was used to induce cell differentiation, cAMP-PKA pathway was blocked, levels of cAMP and rate of it's protein binding decreased. But levels of DG and activity of PKC both increased to the levels of control cells. At this time, PKA-R II distributed only in cytoplasm. These results suggest that harmonious relations of the positive and negative regulation of cAMP-PKA and DG-PKC systems in cells during the proliferation and differentiation of cells. It also showed that positive regulation of PI system may play a leading role in MGc80-3 cells. It let to normal regulation of two signal pathway out of control to remain malignant phenotype of these cells. PMID- 8191798 TI - [Effect of prolactin on production of acid phosphatase in rat prostatic cells and its mechanism]. AB - The present study revealed the effect of prolactin (PRL) and sex steroid hormones on production of prostatic acid phosphatase (PAP) of the immature rat prostatic epithelial cells in serum-free medium. The results showed that PRL significantly stimulated synthesis and secretion of PAP, but failed to synergize with dihydrotestosterone or estradiol. Dihydrotestosterone or estradiol alone did not promote PAP production. Studies on the mechanism of PRL action indicated that adenyl cyclase was not activated in the action of PRL: Synergistic effect between PRL and prostaglandin E2 and F2 alpha was revealed in the stimulation of PAP production, and the effect of PRL could be blocked by indomethacin (a prostaglandin synthesis inhibitor). In conclusion, PRL directly stimulated PAP production of the cultured rat prostatic epithelial cells in serum-free medium and prostaglandin was involved in PRL action. PMID- 8191799 TI - [Lysosomes in the regulation of hormone secretion in the pituitary-adrenal gland axis]. AB - The morphology and morphometrics of the lysosomes and associated structures were studied in hyposecreting corticotrophs and the cells of adrenal cortex zona fasciculata of the rats. Hyposecretion of this two types of the cells in the pituitary-adrenal gland axis was induced by dexamethasone administration. The lysosomes and other hydrolydase-positive structures were identified with CMPase cytochemistry. Quantitative evaluation of the lysosomes, crinophagic and autophagic vacuoles was carried out on the micrographs with MOP-Videoplan system. The results indicated that while inhibited secretion of ACTH accompanied by the increase of the crinophagic and autophagic vacuoles in corticotrophs, inhibited secretion of corticosterone accompanied by the increase of the autophagic vacuoles containing the mitochondria, ER which were steroid-synthesizing apparatus in adrenal cortex cells. The findings in the present study suggested that lysosomal degradation mechanism play a significant role in the regulation of hormone secretion in pituitary-adrenal gland axis. In addition to affirming earlier data that lysosomes took part in the regulation of protein secretion by crinophagy, the main conclusion derived from the present study was that lysosomes also functioned in the regulation of steroid secretion. By the way of autophagy i.e. sequesting and degrading a part of the steroid-synthesizing apparatus, the lysosomes rendered a mechanism in steroid-secreting cells to involve to the regulation process of hormone secretion. This might be an important and general rule as the crinophagy be to the protein-secreting cells. PMID- 8191800 TI - [Hypocrellin B photosensitization effected a change of cytoplasmic free calcium concentration in ascitic hepatoma cells]. AB - The Hypocrellin B (HB) is a new photosensitizer. HB-induced photodynamic changes of cytoplasmic free Ca2+ in ascitic hepatoma (HA) cells were observed using fluorescent calcium indicator Quin 2/AM. It was found that the increase in HB concentrations and exposure time followed by the increase in cytoplasmic free Ca2+. The singlet oxygen and hydroxyl radical generated by HB photosensitization were examined. The lipid peroxidation can be protected by Vit E; the relationship between the plasmic membrane depolarization and cytoplasmic free Ca2+ concentration by HB photodynamic action was investigated. PMID- 8191801 TI - [The relationship between vaccinia virus DNA replication and intermediate filaments]. AB - Various DNA components which were extracted with gentle cell fractionation from the HeLa cells after 4 h vaccinia virus infection were detected by dot hybridization technique. The virus DNA mainly exist in intermediate filament lamina-nuclear matrix complex. With DGD embedment free technique and electron microscopic autoradiography, the newly synthesized virus DNA is found to be associated with intermediate filaments. The results of southwestern hybridization demonstrate that vaccinia virus DNA has specific affinity to intermediate filaments and some nuclear matrix proteins. PMID- 8191802 TI - [Radiation protection effects of sinapine on Drosophila melanogaster in a sex linked recessive lethal test system]. AB - It has been shown that the radiation resistance of some cruciferous plants is related to some natural radiation protection substances in these plants. Sinapine, which has shown radiation protection effects on barley, wheat and mouse, is one of such substances distributed in cruciferous plants. In this paper, the radiation protection effects of sinapine on Drosophila melanogaster in a sex-linked recessive lethal (SLRL) test system were observed. The sinapine solution could be fed to the D. melanogaster (Oregon K). 40 Gy X-irradiation induced SLRL mutation rate of 8.96%. However, if 10 mg/ml sinapine which was found to have no physiological toxicity or harmful effects on its reproductive function, was fed before 40 Gy X-irradiation, the SLRL mutation rate could be reduced to 0.40%, which was within the range of spontaneous SLRL mutation rate of Oregon K Drosophila, i.e. 0-0.4%. The potential of the using of the very strong radiation protection effects of sinapine in anticarcinogenesis was also discussed. PMID- 8191803 TI - [Gene cloning, expression of fusion protein TGF alpha-PE 40 and its inhibition activity on cancer cell growth]. AB - Recombinant plasmid pYX382 and pYX3825 were constructed by fusing the cDNA encoding transforming growth factor type alpha (TGF alpha) to Pseudomonas exotoxin gene (PE) in which the cell recognition domain was deleted. The chimeric proteins produced by host E. Coli cells BL21 transformed by plasmid pYX382 and pYX3825 are termed TGF alpha-PE 40 which reacts with antibody against TGF alpha or antibody against PE in immunoblotting to show a 46 kd protein band reflecting the fusion of 56 kD TGF alpha peptide and 40 kD truncated Pseudomonas exotoxin molecule. An additional signal sequence OmpA was inserted into upstream region of TGF alpha cDNA in plasmid pYX3825 resulting in the partly secreting of expression product into medium and periplasm of the cells. TGF alpha-PE 40 was purified from medium by MONO Q ion exchange column and TSK 250 gel filtration column attached to Pharmacia EPLC system. The TGF alpha-PE 40 molecules showed a very strong activities inhibiting the protein synthesis and killing the cancer cells overexpressing EGF receptor on the cell surface. PMID- 8191804 TI - [The characteristic of the spindle fiber attachment (SFA) enriched fraction from mouse nuclei]. AB - The characteristics of the particulate mouse centromere enriched fraction from isolated nuclei obtained in our laboratory were investigated by indirect immunofluorescence, test of the activity of microtubule organizing center (MTOC), SDS-PAGE, and fluorescence in situ hybridization. Most of the particles of the fraction are complexes of DNA and kinetochore proteins and show MTOC activity. The DNA isolated from the fraction hybridizes the DNA in the regions of the primary constrictions of all chromosomes of ascite cells. The kinetochore proteins of the proteins isolated from the fraction are mainly those with molecular weight of 55 and 59 KD. It is evident that the fraction obtained is a centromere enriched nuclear fraction as indicated in our previous report. PMID- 8191805 TI - Heterochronical patterns of evolution in the transitional stages of vertebrate classes. AB - Transitional forms of the recent classes of vertebrates are only known in paleontology. The well described examples are: Eusthenopteron foordi (Crossopterygii), Ichthyostega and Acanthostega (Labyrinthodontia) between Osteichthyes and Amphibia, Seymouria baylorensis (Amphibiosaria) between Amphibia and Reptilia, Archaeopteryx lithographica (Archaeornithes) between Reptilia and Aves, and the mammal-like reptiles Pelycosauria, Therapsida and Cynodontia between Reptilia and Aves, and the description of their phylogenetical heterochronies in terms of peramorphosis and paedomorphosis shows the progressive role of the motorial, especially the locomotorial organ systems and their functions in comparison with the retarded evolution of the axial system, especially the skull and central nervous system. The evolution of the Hominidae shows the same rule. The evaluation of these transitional forms in their fossil context reveals them as inhabitants of biotopes situated in the border areas of coastal and shore landscapes of marine, brackish or fresh water. These biotopes have obviously favoured the innovations on the high taxonimic level of macro evolutionary characteristics. PMID- 8191806 TI - Homologies in the fossil record: the middle ear as a test case. AB - This paper examines the middle ear of fossil living animals in terms of the homologies which have been drawn between its parts in different vertebrate groups. Seven homologies are considered: 1, the middle ear cavity/spiracular pouch; 2, the stapes/hyomandibula; 3, the stapedial/hyomandibular processes; 4 the tympanic membrane; 5, the otic notch; 6, the fenestra ovalis; 7, and the stapedial/hyomandibular foramen. The reasons leading to assessments of homology are reviewed. Homologies 1 and 2, based largely on embryological evidence, are fairly robust, though there are arguments about the details. Homologies 3, 4 and 5 stem from ideas about early tetrapod evolution, and were influenced by contingent factors including the order and time of discovery of early fossil taxa, and perceptions of their phylogeny which resulted from this. They were also influenced by ideas of the evolution of terrestriality among tetrapods. Most of the conceptions have been overturned in recent years by new fossil discoveries and new ways of looking at old data. Homology 6 has been little considered. One possible hypothesis, placed in a strictly 'archetypal' theoretical framework has been ignored but deserves consideration on other grounds. Homology 7 depends on how tetrapods are characterised, not a question which has posed difficulties until recently, but which is likely to with the discovery of intermediate fossil forms. PMID- 8191807 TI - Ancestors and homology (the origin of the tetrapod limb). AB - Current issues concerning the nature of ancestry and homology are discussed with reference to the evolutionary origin of the tetrapod limb. Homologies are argued to be complex conjectural inferences dependent upon a pre-existing phylogenetic analysis and a theoretical model of the evolutionary development of ontogenetic information. Ancestral conditions are inferred primarily from character (synapomorphy/homology) distributions within phylogeny, because of the deficiencies of palaeontological data. Recent analyses of tetrapod limb ontogeny, and the diverse, earliest morphologies known from the fossil record, are inconsistent with typological concepts such as fixed ancestral patterns or bauplans, emphasising the incompatibility of these with evolutionary continuity. The evolutionary origin of the tetrapod limb is also examined in the light of its recent discussion in developmental genetics. While this field promises to reveal more of the fundamental ontogenetic content of homology (identity), at present it is concerned mostly with the abstraction of a new set of types, rather than investigating diversity and change. PMID- 8191809 TI - Indoor air pollution and asthma. PMID- 8191808 TI - The effect of vitamin A (retinoids) on pattern formation implies a uniformity of developmental mechanisms throughout the animal kingdom. AB - Retinoids are low molecular weight, lipophilic derivatives of vitamin A which have a profound effect upon the development of a diverse array of animals. Here, I review these effects on Invertebrates: a colonial hydroid, a colonial ascidian, and Vertebrates: the regenerating amphibian limb, the developing chick limb bud, the regenerating amphibian tail, the anteroposterior axis of the early embryo, the developing chick embryo skin. There is a striking uniformity of effect of retinoids on pattern formation when applied to these diverse organisms. The majority react by being posteriorized in their development, although additional effects can also be seen. Several hypotheses which can explain these results are discussed along with the deduction that they lead to: retinoids may be components of a universal developmental mechanism or they may simply act in a similar way to alter a universal developmental mechanism. In either case the experimental analysis of retinoid effects on development has important implications for the evolution of developmental mechanisms. PMID- 8191810 TI - A massive, near-fatal cocaine intoxication in a body-stuffer. Case report and review of the literature. AB - The last decade an increase has been seen in drug smuggling. Body-packing and body-stuffing are the terms used for intracorporeal concealment of illicit drugs (mainly cocaine and heroine, but sometimes also amphetamines and cannabinoids). These body-packets are especially prone to rupture. In order to avoid systemic cocaine toxicity, which can involve nearly every organ and therefore nearly every subspecialty of medicine urgent diagnosis is necessary. Obtaining a detailed history remains crucial. Further clues to diagnosis are given by the urinary drug concentrations and the benzoylecgonine/cocaine ratio in urine. Plain abdominal films, CT and contrast studies of the bowel can be helpful in identifying the package but are of limited value. In addition to activated charcoal, polyethylene glycol-electrolyte lavage solution, enteral feeding and laxatives (not paraffin) can be used to eliminate the body-package by enhancing bowel transit. Alkalinisation of gastric fluids enhances hydrolysis to cocaine's major inactive metabolite benzoylecgonine. If the package fails to progress through the gut or if mechanical obstruction occurs surgical removal is indicated. In no way endoscopic removal of the package should be attempted. Systemic symptoms should be treated by blocking the sympathetic overreactivity; this can be done with diazepam (Valium), labetalol (Trandate) or esmolol. Flumazenil (Anexate), lidocaine (Xylocaine) and pure beta-blockers like propranolol (Inderal) are to be avoided. PMID- 8191811 TI - Kaposi's sarcoma presenting as generalized lymphedema. AB - We present a HIV-1 seropositive patient with generalized lymphedema, due to a rare lymphangiomatous variant of Kaposi's sarcoma, successfully treated with interferon-alpha. The clinical presentation and treatment possibilities of Kaposi's sarcoma are reviewed. PMID- 8191812 TI - A case of tracheal fibrolipoma. AB - We report the case of a tracheal fibrolipoma in a 40-year-old man successfully treated by laser photocoagulation. The clinical and pathological aspects, as well as the therapeutical options of this rare upper airway benign tumor are discussed. PMID- 8191813 TI - [Late diagnosis of tetralogy of Fallot in an asymptomatic adult]. AB - The authors report a case of Fallot's tetralogy found in an asymptomatic adult patient. Echocardiography and cardiac catheterization confirmed the diagnosis. Life expectancy without surgery is usually short and our patient's survival is therefore uncommon. This case probably represents the oldest patient with uncorrected tetralogy found in the literature. PMID- 8191814 TI - Hyperchloremia and a negative anion gap in a stuporous woman. PMID- 8191815 TI - Random rescreening of cytologic smears: a practical and effective component of quality assurance programs in both large and small cytology laboratories. PMID- 8191816 TI - Fine needle aspiration biopsy of the spleen. A useful procedure in the diagnosis of splenomegaly. AB - This study analyzed a series of 140 consecutive fine needle aspiration biopsies of the spleen (sFNAB) collected over a period of nine years. sFNABs were performed by the authors using a 22-gauge spinal needle, and 23-gauge needle in pediatric patients, with a subdiaphragmatic approach. Ultrasound assistance was utilized in 35 cases. Four of the cytocentrifuge specimens were also prepared with part of the aspirated material and used for immunocytochemical staining. Study of these biopsy specimens revealed various benign conditions, such as white pulp hyperplasia, myeloid metaplasia, storage disease, and granulomatous processes and abscesses. Malignant neoplasms were represented by non-Hodgkin's and Hodgkin's lymphomas, leukemias, malignant histiocytoses and metastases. sFNAB was the only diagnostic procedure employed for the morphologic assessment of 60 benign and of 2 malignant cases. In all the other cases sFNAB gave the first diagnosis that was confirmed on surgical specimens. In 2 cases splenic bleeding occurred; one of them required splenectomy. Diagnostic and technical problems are discussed. The authors consider sFNAB a useful procedure, especially in the study of hematologic disorders and in all cases in which splenomegaly is not related or correlated with any clinical finding. PMID- 8191817 TI - Consistency of reporting endocervical cells. An intralaboratory and interlaboratory assessment. AB - A study of the intralaboratory and interlaboratory consistency of reporting endocervical cells on cytologic smears is presented. Two sets of 40 slides were compiled from previously reported material. Twenty-two laboratories each reported one set of the slides according to a single coding schedule. The intralaboratory agreement on the endocervical cell code was 80%. Considerable variation was evident between laboratories. While only 14% of the 80 slides received a unanimous endocervical code across the 11 reviewing laboratories, 73 of the 80 slides had agreement by at least 7 of the 11 reviewing laboratories. If the coding option "minor reactive and inflammatory changes in endocervical cells" was amalgamated with the coding option "normal endocervical cells present," a substantial improvement in the level of agreement resulted. The probability of agreement between laboratories did not vary according to whether the subsequent histology/cytology was reported as negative or as a low grade abnormality. PMID- 8191818 TI - Brush vs. spatula for cervical smears. Histologic correlation with concurrent biopsies. AB - In this study we compared the results of 1,293 brush smears obtained between April 23, 1990, and April 22, 1991, with those of 1,304 consecutive spatula smears from 1989. As expected, 94.1% of brush smears revealed the presence of endocervical cells as compared to 63.04% of the spatula smears (P < .0001). The number of "normal" cases was significantly (P < .001) lower in the brush smears (58.2% for the brush vs. 73.7% for the spatula). A significantly larger number (P < .001) of "abnormal" cases and low and high grade squamous intraepithelial lesions (moderate, severe, carcinoma in situ) were demonstrated in the brush smears. In the second part of the study the results of 547 brush smears with accompanying cervical biopsies obtained during the same period were studied for concordance of interpretation and were compared with 421 biopsy-accompanied spatula smears. Of the brush cases, 17.6% cytologically reported as high grade squamous intraepithelial lesions had low grade squamous intraepithelial lesions or reactive or normal histology. This discrepancy was significantly lower (P < .05) in spatula cases (8.9%). These findings suggest that in this series, although brush sampling yielded a higher pickup, it led to a tendency toward overinterpretation by cytopathologists. PMID- 8191819 TI - Experience with Endopap endometrial sampling in the cytodiagnosis of endometrial carcinoma and its precursor lesions. I. A correlative cytologic-histologic hysteroscopic diagnostic pilot study. AB - From June 1 through December 3, 1991, 146 women were referred to the Gynecology Outpatient Clinic of Nahariyya Medical Center for uterine bleeding and pathologic conditions. Their ages ranged from < 40 (26 patients) to > or = 60 (18 patients), with 60 (41%) in the 40-49 age group. An Endopap endometrial sampling pilot study was undertaken to find a correlative index between cytologic, histologic and hysteroscopic sampling methods as well as to investigate the possibility that Endopap sampling could avoid excessive use of nontherapeutic dilation and curettage. In 118 patients for whom concomitant cytologic and histologic specimens were available there was no statistically significant difference between the number of correct cytologic and histologic diagnoses of intrauterine pathology. Cytodiagnostic accuracy of the Endopap samples was expressed in terms of sensitivity (68.2%), specificity (80.7%), predictive value of a malignant test result (100%) and predictive value (PV) of an abnormal (hyperplasia) test result (73.2%). The lower values for sensitivity, specificity and PV in this study as compared with those in the literature were probably due to three attenuating factors: the relatively small number of patients (146), the fact that the cytodiagnostic accuracy for hyperplasia and precursor lesions of endometrial carcinoma is significantly lower than for histologic diagnosis, and the presence of 15 (10.3%) inadequate cytologic specimens. The results did tend to concur with the range of reported results. It is recommended that Endopap sampling be employed in cases of medically and anatomically contraindicated dilation and curettage--e.g., cervical canal stenosis and intrauterine adhesions (Asherman's syndrome)--in monitoring perimenopausal and postmenopausal patients on estrogen replacement therapy and in obese women, diabetics and hypertensives at risk of developing endometrial hyperplasia. The study also showed that the combined hysteroscopic and Endopap techniques could result in increased rates of sensitivity and specificity. PMID- 8191820 TI - Erythrocyte folate levels, oral contraceptive use and abnormal cervical cytology. AB - The initial hypothesis of this study was that folate depletion is a risk factor for human papillomavirus infection and cervical epithelial cell abnormalities, including dysplasia. The prevalences of low erythrocyte folate levels (defined as < 140 ng/mL erythrocytes and determined by the growth of Lactobacillus) were measured in 250 University of California at Los Angeles students. Among oral contraceptive users, low erythrocyte folate was a risk factor for an abnormal cytologic smear in both benign atypia and squamous intraepithelial lesions. Odds ratios were statistically significant for biopsied women who did not have condyloma and for those who did not have squamous intraepithelial lesions but not for those with histologically confirmed intraepithelial lesions. Low erythrocyte folate was a risk factor for a positive Virapap result in oral contraceptive users. If the folate effects are causal, the findings suggest that erythrocyte folate levels should be higher in oral contraceptive users than in nonusers to protect against an abnormal cytologic smear. PMID- 8191821 TI - Cytologic features of ependymomas in smear preparations. AB - Since the cytologic features of brain smear preparations have not been described adequately in the literature, 13 histologically proven ependymomas with diagnostic smear preparations were reviewed. The series also included cases of myxopapillary ependymoma and papillary ependymoma. The typical cytologic appearance consisted of dichotomous patterns of small, epithelium-like cells merging with bipolar, fibrillated cells with pseudo-rosette formations. It is believed that careful scrutiny of intraoperative preparations allows one to make a distinction between pilocytic astrocytoma, fibrillary astrocytoma and metastatic carcinoma. PMID- 8191823 TI - Nuclear shape and axillary metastases in breast cancer. Analytic morphometry of aspiration smears. AB - The aim of this work was to seek quantitative parameters other than dimensions to describe nuclear shape and, by this means, to determine the sum of contour irregularities and large asymmetries and seek a connection with the biologic behavior of the tumor. Nuclei of the cells obtained from 57 aspiration smears of breast cancers were studied. Dimensional parameters (area, perimeter, maximum diameter and roundness factor) and analytic parameters were computed by the Shape Analytical Morphometry software system to evaluate both contour irregularities and asymmetry of nuclear shape. All the tumors were subdivided according to their diameters into two groups: T1 tumors, the maximum diameter of which was < 2 cm (18 cases), and T2 tumors, the maximum diameter of which was > 2 cm and < 5 cm (39 cases). Among T1 tumors, both dimensional and analytic parameters were highly significant (P < .001) in distinguishing tumors with (N+) and tumors without (N-) axillary metastases, while among larger tumors (T2) only the analytic parameters showed degrees of significance, albeit variable. It could be inferred that in smaller tumors, aggressiveness is related to an increase in nuclear dimensions and shape distortions more so than in larger tumors. PMID- 8191822 TI - Immunohistochemical detection of ras p21 oncoprotein in breast cancer imprints. AB - We examined the expression of ras p21 oncoprotein using monoclonal antibody Y13 259 and applied the streptavidin-biotin method. A total of 79 imprints of breast lesions were taken during frozen section. Our purpose was evaluation of the staining intensity, at the cellular level, without the technical disadvantages of formalin-fixed, paraffin-embedded tissues. Of the 79 imprints examined, 37 were carcinomas of ductal origin (not otherwise specified type), 8 were lobular and 3 mixed. Additionally, 20 imprints from adjacent normal tissue as well as 11 fibroadenomas (simple and hyperplastic) were assessed. Our results showed the following: (1) the positivity of all cancer cells ranged from + to + + +, (2) positivity did not show any significant difference among cancer types, (3) in increasing the tumor grade, staining intensity was increased, (4) whenever benign epithelial cells were present, their expression was low or mild, (5) only hyperplastic fibroadenomas showed weak positivity, and (6) almost all the inflammatory components were constantly negative. PMID- 8191824 TI - Fine needle aspiration cytology of Wilms' tumor. A study of 17 cases. AB - The cytologic features of 17 cases of Wilms' tumor are described. All three elements identifiable histologically are usually present in the fine needle aspiration smears. In our cases the blastemal component predominated, with varying degrees of epithelial and stromal differentiation, which was identifiable in the form of skeletal and smooth muscle. Early epithelial differentiation was identified as rosette-like and gland-like structures, groups of cells with peripheral palisading and spherical, tightly bound clusters of cells. More differentiated epithelial cells were seen individually, in small, loose clusters, in sheets with a honeycomb appearance and as elongated tubules. Coarse, magenta, granular material was seen in the background of the smears in the majority of our cases. Fine needle aspiration under ultrasound guidance to accurately localize the tumor and a posterior approach to avoid peritoneal spillage are recommended. In difficult cases, a cell block of the aspirated material is a useful adjunct. PMID- 8191825 TI - Interphase nucleolar organizer regions in the evaluation of serosal cavity effusions. AB - Argyrophilic nucleolar organizer regions (AgNORs) were determined in 38 pleural and peritoneal effusions from patients with malignant solid tumors. The results were correlated with the cytologic diagnosis and flow cytometric DNA analysis to determine the diagnostic potential of this technique. Cytologically, 13 effusions were benign, 23 malignant and 2 indeterminate (5.2%). The mean AgNOR counts for benign, malignant and indeterminate specimens were 2.99, 3.94 and 3.50, respectively. Low AgNOR counts (< 4.0) were obtained in 12 (90.9%) of the 13 benign, 16 (60.0%) of the 23 malignant and 1 of the indeterminate effusions. High AgNOR counts (> 4.0) were noted in 1 (9.1%) of the benign, 7 (35.0%) of the malignant and 1 (5.0%) of the indeterminate specimens. There was no statistically significant difference between the AgNOR count in benign and malignant effusions (P = .48). All 10 benign effusions analyzed with flow cytometry were DNA diploid. Seven (35.0%) of the 20 cytologically malignant effusions were DNA aneuploid, and 13 (70.0%) were DNA diploid. Proliferative activity was low (< 7.0%) in 23 cases and high (> 7.0%) in 7 (6 malignant and 1 benign). There was no statistical correlation between the AgNOR count and DNA ploidy (P = .11) or proliferative activity (P = .23). We conclude that the AgNOR method lacks sensitivity as a diagnostic tool for serosal cavity effusions. PMID- 8191826 TI - Cytologic findings in rectovaginal fistulae. AB - This study was designed to evaluate the cytologic components in vaginal smears from women with rectovaginal fistulae and consisted of smears from 23 women. The etiology of the fistulae was complications of irradiation (14 cases), neoplasms (7 cases) and pelvic abscess or inflammation (2 cases). Thirteen cases (15 smears) contained benign colonic cells compatible with rectovaginal fistulae; 10 cases (17 smears) did not. Fecal material was present in 7 cases, 5 of which also contained colonic glandular cells. Changes of irradiation were noted in 2 cases and reparative changes in 2 others. In the 7 patients with carcinoma, malignant cells were present in 2 cases of fistulae due to colonic adenocarcinomas. In this study, rectovaginal fistulae could be documented in vaginal cytology in 65% of patients with the condition. PMID- 8191827 TI - Cytomorphologic panorama of cysticercosis on fine needle aspiration. A review of 298 cases. AB - Definitive identification of detached hooklets, scolex and fragments of the spiral wall of Cysticercus cellulosae on fine needle aspiration smears was documented. A critical review of aspirates from 200 diagnosed and 98 suspected lesions of soft tissue and intramuscular cysticercosis was done. Characteristic fragments of bladder wall cytomorphologically corresponding to viable or partially necrotic lesions were seen in 203 cases. Identification of fragments of an invaginated larva (i.e., hooklets, scolex or spiral wall) established the diagnosis in 33 of the suspected lesions. Cytomorphologically all these cases were from either necrotic or calcified lesions. In necrotic lesions with eosinophils, a careful search for fragments of the invaginated portion of the larva should be made. PMID- 8191828 TI - Fine needle aspiration cytology vs. needle core biopsy of soft tissue tumors. A comparison. AB - Fine needle aspiration (FNA) cytology is an effective modality in the diagnosis of soft tissue lesions. Previous studies compared FNA with surgical biopsies and reported high sensitivity and specificity rates. No study has evaluated the diagnostic yield of FNA to that of needle core biopsies (NCBs). One hundred seventeen FNAs were performed by our clinical staff for soft tissue lesions (1980 1992). The FNAs were divided into three categories: diagnostic 53 (37 sarcoma, 16 benign); unsatisfactory, 44; normal/inflammatory cells present, 20. Of these, 59 had concomitant NCBs: 37 on patients with sarcoma on FNA, 22 on unsatisfactory FNA and none on those with normal/inflammatory cells (followed clinically). There was 100% correlation between FNA and NCB when sarcoma was diagnosed. In 7 of these cases, the NCB further specified the type of sarcoma. No NCBs were employed to confirm the diagnosis of benign tumor on FNA; excisional biopsies showed a total correlation. The 22 NCBs for unsatisfactory FNA yielded 15 sarcomas, 2 fibromatosis and 5 benign lesions. Seventeen patients with unsatisfactory FNA had surgical biopsies (3 sarcoma, 14 benign), and 5 were lost to follow-up. In our experience, diagnostic FNA gave a yield identical to that of NCB, and the latter did not contribute to patient management. Core biopsies may have the advantage of subtyping selected sarcomas diagnosed by FNA. Unsatisfactory FNA should be evaluated further by a repeat aspirate or NCB. Performance of FNA by cytopathologists can reduce the number of unsatisfactory specimens and allow repeat aspiration. In our study most of the unsatisfactory FNAs were from retroperitoneal and pelvic lesions, were performed under radiographic guidance and could have been minimized by immediate cytologic assessment. Many of these lesions, however, may be as readily accessible via NCB as they are via FNA. Utilization of each of these modalities and of their full benefits ultimately depends on the proper clinical setting and the experience of the clinician and pathologist. PMID- 8191830 TI - Fine needle aspiration diagnosis of benign metastasizing leiomyoma of the lung. A case report. AB - Percutaneous fine needle aspiration biopsy was performed on a woman with multiple bilateral lung nodules. The cytology and histology showed a benign spindle cell tumor compatible with benign metastasizing leiomyoma. The patient had a history of hysterectomy 14 years earlier for a cellular leiomyoma with atypia. No significant mitosis was present in either the uterine tumor or lung metastasis. PMID- 8191829 TI - Localization of double, roentgenographically occult lung cancer. Cytologic findings from selective brushing of all segmental and subsegmental bronchi. AB - Using selective brushing of all segmental and subsegmental bronchi, six patients were diagnosed as having synchronous, double, roentgenographically occult lung cancers. Experienced bronchoscopists failed to detect four "second cancer" lesions in six patients. The appearance of atypical cells as shown by cytologic examination indicated the probability of the presence of cancer in the examined bronchus. Single cancer cells or tiny clusters of cells with orangeophilic cytoplasm can appear in specimens obtained from all bronchi, and such cells should not be considered to have originated in the bronchi under examination. Medium-sized or large clusters of cancer cells without degeneration and with basophilic cytoplasm appear only in specimens obtained from bronchi in which a cancer lesion exists, and thus they should be considered to have originated in the bronchi under examination. Cancer cells with orangeophilic cytoplasm in clusters should be considered to have originated in unknown locations. To determine the origin of such cells, one must compare the specimens with those obtained from other segmental and subsegmental bronchi. Our findings suggest that selective brushing of all segmental and subsegmental bronchi is a useful method of detecting unrecognizable second cancers and that the method should be employed for all patients with positive sputum cytology. PMID- 8191831 TI - Cytologic diagnosis of measles pneumonia in a bronchoalveolar lavage specimen. A case report. AB - An immunocompromised employee of our medical center contracted measles during an epidemic and subsequently died of giant cell pneumonia. In this report we discuss the cytologic diagnosis of measles pneumonia and the differential diagnosis of multinucleate giant cells in lung cytology specimens. In the appropriate clinical setting, inclusion-bearing syncytial epithelial giant cells in lung are virtually pathognomonic of measles infection. Cytologic specimens can provide an important early diagnosis. PMID- 8191832 TI - Morphometric comparison of a metastatic transitional cell carcinoma simulating squamous metaplasia in sputum cytology. A case report. AB - Sputum cytology was performed to rule out primary lung carcinoma in a patient with a cough of recent onset, an infiltrate on chest roentgenography and a history of bladder and prostate carcinoma. The cytology was interpreted correctly as metastatic transitional cell carcinoma. Review of the cytology by other pathologists without the benefit of the previous history or histologic material resulted in interpretations of reactive/metaplastic tissue. A morphometric comparison of nuclear parameters between the cells in the sputum and the squamous metaplastic cells seen in the sputum of a patient with viral pneumonia from our archives was performed. Evaluation of the current sputum cytology without the benefit of clinical information or additional studies may have led to a false negative diagnosis. PMID- 8191833 TI - Pulmonary metastasis from histologically benign giant cell tumor of bone. Report of a case diagnosed by fine needle aspiration cytology. AB - The cytologic features of pulmonary metastasis from a histologically benign giant cell tumor of bone are reported. The patient had undergone curettage of a benign giant cell tumor of the humerus two years earlier. Aspiration of a pulmonary mass yielded a cellular population of mononuclear stromal cells admixed with a smaller population of binucleate forms and occasional giant cells. Vacuolation and granulation of the stromal cells are cytologic features seen commonly in giant cell tumors of bone, but in the lung these features may deceptively mimic the appearance of pulmonary macrophages. Video thoracoscopic wedge resection of the metastatic lesion was performed subsequently. PMID- 8191834 TI - Crystals in pulmonary cytologic preparations in association with aspiration of barium. A case report. AB - Crystals were found in a pulmonary cytologic preparation in association with the aspiration of barium. This type of event has not been described previously, although rare occurrences of crystals in pulmonary cytology specimens in association with Aspergillus infection and other situations have been reported. We recommend that patients suspected of aspiration be given no oral substances for at least 12 hours before bronchoscopy. PMID- 8191835 TI - Myoepithelioma of the parotid. Report of a case initially examined by fine needle aspiration biopsy. AB - Fine needle aspiration (FNA) biopsy of a large, deep lobe of a parotid mass revealed a uniform population of small, spindled cells with no distinctive cytologic features. Biopsy and later resection of the mass revealed a myoepithelioma. Myoepithelioma is a rare lesion, occurring most commonly in the parotid gland. To date, the FNA description of myoepithelioma has been limited to one report of a lesion in the breast. We report the FNA findings of this tumor arising in the parotid, with histologic and electron microscopic confirmation. PMID- 8191836 TI - Initial diagnosis of disseminated cryptococcosis and acquired immunodeficiency syndrome by fine needle aspiration of the thyroid. A case report. AB - Fine needle aspiration of the thyroid was performed on a patient with an enlarged, solid gland, revealing numerous budding yeasts of Cryptococcus neoformans. Special stains and culture confirmed the organism. This unexpected finding led to the diagnosis of disseminated cryptococcosis and human immunodeficiency virus infection. PMID- 8191837 TI - Adenomyoepithelioma of the breast. Report of a case with fine needle aspiration cytology and histologic, immunohistochemical and ultrastructural correlation. AB - A case of adenomyoepithelioma of the breast was studied by cytology, histology, immunohistochemistry and electron microscopy. Aspiration cytology of the tumor showed sheets and tubular-type clusters of cohesive, regular polygonal cells with abundant, fairly well preserved, pale, granular to finely vacuolated, clear cytoplasma and a low nuclear/cytoplasmic ratio. The nuclei were small, round and monotonous, with dispersed chromatin and small or inconspicuous nucleoli. Acinus formation was striking: an occasional gland showed a suggestion of an inner layer of cells with denser cytoplasm surrounded by an outer mantle of paler cells. The histologic, immunohistochemical and ultrastructural findings confirmed the two cell populations, constituting an inner epithelial and outer myoepithelial component, both participating in the neoplastic process. The differential diagnoses of various breast lesions with somewhat similar cytologic features are discussed. PMID- 8191838 TI - Aspiration cytology of malignant intraductal myoepithelioma of the breast. A case report. AB - The cytologic features of a fine needle aspiration biopsy of a malignant intraductal myoepithelioma of the breast are described. On cytology the tumor cells were shed in cohesive groups consisting of ill-defined polygonal and spindle cells. The latter, which had centrally located, cigar-shaped nuclei, showed a fascicular pattern. Despite cellular multilayering, there was a halo like transparency around the nuclei, suggesting that many cells had clear or pale cytoplasm. Mild nuclear atypia was occasionally present. Mitotic figures were also observed. With immunostaining, clustered cells showed a diffuse positive reaction for alpha smooth muscle actin (alpha-SM-actin). The tumor cells proliferated intraductally, as in a conventional intraductal carcinoma with a comedo or solid pattern. Characteristically, zones of clear, polygonal cells were situated at the ductal periphery. Toward the center of each duct, tumor cells were transformed into nonclear cells, and some were further transformed into spindle cells that tended to form fascicles. Immunohistochemically, most of the tumor cells expressed alpha-SM-actin. PMID- 8191839 TI - Alpha-mannosidosis. Report of a case with morphologic, cytologic and immunohistochemical considerations. AB - We report the histopathologic features of the knee bone and synovium and the cytologic features of the synovial fluid from a patient with alpha-mannosidosis. The synovium showed marked papillary hyperplasia with infiltration of foamy histiocytes containing periodic acid-Schiff-positive, diastase-resistant material. Severe degenerative changes were seen in the knee bone. The synovial fluid showed increased numbers of macrophages containing periodic acid-Schiff positive, diastase-resistant material. The differential diagnostic considerations in the synovial fluid are also discussed. PMID- 8191840 TI - Secretory breast carcinoma in a man diagnosed by fine needle aspiration biopsy. A case report. AB - Preoperative aspiration biopsy of a breast tumor in a 20-year-old male resulted in a diagnosis of secretory breast carcinoma. The material obtained from aspiration biopsy was also used for electron microscopic, immunocytochemical and flow cytometric analysis. The characteristic light microscopic features were numerous large secretory vacuoles containing proteinaceous material, which was also seen in the background of the smear. Electron microscopy revealed numerous intracellular lumina and some intercellular ones filled with secretory material as well as membrane-bound vacuoles. Immunoreactivity was positive for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, alpha lactalbumin and vimentin. Flow cytometric analysis showed the tumor to be diploid. The affected breast and tumor were resected, and the cytologic diagnosis was confirmed histopathologically. The cytomorphologic features of secretory breast carcinoma seem to be alike in men and women and are sufficiently characteristic to permit a definitive preoperative diagnosis from fine needle aspiration biopsy smears. The differential diagnosis with other tumors is discussed briefly. PMID- 8191841 TI - Simultaneous relapse of liver cell carcinoma and non-Hodgkin's lymphoma in the liver. Report of a case with diagnosis by ultrasonically guided fine needle aspiration biopsy. AB - A 50-year-old man was diagnosed with non-Hodgkin's lymphoma (NHL) in 1980; he was treated with chemotherapy and achieved complete remission. Six years later he reported upper abdominal pain. Ultrasound (US) showed a 3-cm mass in the right lobe of the liver. Needle aspiration showed hepatocellular carcinoma (HCC). The patient was treated with radical resection of the tumor. Three years later (June 1989), abdominal US showed two lesions in the right lobe of the liver. Needle aspiration and tissue core biopsy showed NHL in one lesion and HCC in the other. The lymphomatous lesion resolved after chemotherapy. The patient died 30 months later (January 1992) from a gastrointestinal hemorrhage; the NHL was in complete remission. This case of the simultaneous presence of HCC and hepatic lymphoma is, to our knowledge, the first diagnosed in vivo. PMID- 8191842 TI - Fine needle aspiration cytology of peripheral lymph node cryptococcosis. A report of three cases. AB - Aspiration cytology of lymph nodes allows rapid diagnosis of disseminated cryptococcosis. Three cases of lymph node cryptococcosis diagnosed by aspiration cytology in three patients with acquired immunodeficiency syndrome are presented. The organisms were easily seen with a routine modified Wright and Papanicolaou stain as variably sized yeasts, 5-15 microns in greatest diameter, with thick capsules. Many of the organisms showed narrow base budding. In one case occasional pseudohyphae were observed. The diagnoses were confirmed easily with mucicarmine stain. PMID- 8191843 TI - Nasal scrape cytology in the diagnosis of Wegener's granulomatosis. A case report. AB - Wegener's granulomatosis (WG) is a potentially fatal disease in which early diagnosis and administration of immunosuppressive agents is essential to successful treatment. The disease is characterized by necrotizing and granulomatous inflammation and vasculitis of the respiratory tract and kidney. The variety of clinical presentations often makes the diagnosis difficult. We present a case of WG in a 24-year-old male in whom the diagnosis was first suggested after cytologic examination of a nasal scrape for sinusitis. The smears showed numerous neutrophils and occasional multinucleate histiocytic giant cells. Reactive epithelial cells from the respiratory mucosa were also present. No organisms were identified on Gram or acid-fast stain. Considering the clinical setting, the diagnosis of WG was suggested. Subsequent renal biopsy revealed necrotizing and crescentic glomerulonephritis, and the patient was successfully treated with cyclophosphamide. This case illustrates a rapid and noninvasive method by which the diagnosis of WG may be suspected early in the course of the disease. PMID- 8191844 TI - Atypical lymphocytes in spinal fluid resembling posttransplant lymphoma in a cardiac transplant recipient. A case report. AB - The interpretation of atypical leukocytes in the cerebrospinal fluid (CSF) poses diagnostic problems. We present a case of a heart transplant patient whose CSF contained highly atypical lymphocytes that were originally interpreted as "suspicious for lymphoma." Because the patient was clinically thought to have disseminated zoster, he was treated with acyclovir, and the atypical infiltrate resolved. This case exemplifies the extreme difficulty of interpreting cerebrospinal fluid in immunosuppressed patients who are at risk of developing posttransplant lymphoproliferative disorders. PMID- 8191845 TI - Fine needle aspiration cytology of central giant cell granuloma of the jaw. A report of two cases. AB - Two patients with recurrent central giant cell granuloma (CGCG) who underwent fine needle aspiration biopsy are reported. This lesion has a distinct clinicoradiologic profile and occurs almost exclusively in the mandible and/or maxilla of young individuals. The essential cytologic findings included a dual cell population consisting of mononuclear stromal cells and multinucleate giant cells. These features were considered not specific for the diagnosis of CGCG and are identical to those of osteitis fibrosa cystica and giant cell tumor of bone. If the features are taken together with the clinical, radiologic and laboratory data, the diagnosis of CGCG is possible. The utility of osseous fine needle aspiration biopsy and the clinical, radiologic and cytologic findings of bone lesions containing giant cells are discussed. PMID- 8191846 TI - Fine needle aspiration of invasive cribriform carcinoma with benign osteoclast like giant cells of histiocytic origin. A case report. AB - We report the fine needle aspiration findings, with histologic confirmation, of a case of invasive cribriform carcinoma of the breast with benign osteoclast-like giant cells. We suggest that this diagnosis be considered when low to moderate grade malignant epithelial cells and numerous benign giant cells are seen in fine needle aspirates of the breast. We also confirmed immunohistochemically the histiocytic origin of the benign giant cells. PMID- 8191847 TI - Disseminated histoplasmosis diagnosed by needle aspiration: differential diagnoses. PMID- 8191848 TI - Acquired immunodeficiency syndrome transmission to neonates. PMID- 8191850 TI - Megakaryocytes in bronchial brush cytology. PMID- 8191849 TI - Bancroftian microfilariae in ascitic fluid. PMID- 8191851 TI - Fine needle sampling without suction in intraabdominal lesions: comparison with fine needle aspiration. PMID- 8191852 TI - Nutritional therapy in liver disease. AB - Nutritional inadequacies are frequent in patients with liver damage, specially in those with advanced chronic liver disease, and this fact, as in other pathological circumstances, may influence their clinical evolution and outcome. Therefore, nutritional therapy may play an important role in the management of these patients. The present paper will deal with some aspects of the nutritional management in patients with liver disease. Special emphasis will be paid to the role of artificial nutritional support in the treatment of acute alcoholic hepatitis, the current status of artificial nutrition in advanced cirrhosis, and some nutritional implications in the management of hepatic encephalopathy. PMID- 8191853 TI - Paradoxical contraction of pelvic floor muscles: clinical significance. AB - Paradoxical contraction of pelvic floor muscles during defecation straining has been said to be a cause of constipation and difficulty in passing feces. Nevertheless, controversies about its clinical significance still remained. Twenty patients with constipation and electromyographic evidence of paradoxical contraction of both puborectalis and external anal sphincter were investigated. An anorectal manometry performed in 17 confirmed the paradoxical contraction in 13 (76%). Electromyography revealed neurogenic signs in 11. Defecography demonstrated the paradoxical contraction in 6 only, but, together with barium enema and colon transit time, showed associated anorectal disorders in 9 patients. Twenty control patients were also studied. None had difficulty defecating. Nevertheless, 8 of them (40%) had paradoxical contraction. These observations suggest that paradoxical contraction of pelvic floor muscles may by asymptomatic and that another cause of emptying difficulties has always to be looked for. PMID- 8191854 TI - Techniques and results of variceal pressure measurements. AB - Pressure in esophageal varices can be measured by puncture of a varix, or using an endoscopic gauge or by means of an endoscopic balloon. Puncture is usually regarded as an invasive technique in contrast with the other two. Puncture technique has been considered as the "gold standard" to which other methods of measurement should be compared but its results have not been analyzed critically until recently. The pressure gauge has given reliable pressure measurements in vitro, but results in vivo are still controversial. The new technique using an endoscopic balloon has been assessed in vitro and in vivo, and has given reliable pressure measurements. Studies have been performed by either using the needle puncture technique or the endoscopic gauge. It has been shown that pressure in esophageal varices varies during respiratory cycle, but that the pressure gradient between varices and esophageal lumen (transmural pressure) remains unchanged. Similarly, during Valsalva's maneuver, transmural pressure remains unchanged in most cases in spite of a rise in variceal pressure. Pressure in esophageal varices correlated with portal pressure in spite of possible difference in their respective values. The effects of pharmacological substances on variceal pressure has also been investigated using the above mentioned techniques. Non-invasive techniques should allow measurement and studies on a broader scale. PMID- 8191855 TI - Transrectal ultrasonographic examination of the anal sphincter. AB - Transrectal Ultrasonography (TRU) provides an excellent imaging of the rectal wall, the perirectal structures (1) and especially of the anal sphincter (2,3). We used a rigid endorectal probe with a linear and a radial ultrasonic window, and with a frequency of 5 MHz (model IUV 5060; Toshiba, Japan). The linear scanning provided a better imaging of the anal sphincter and was preferred to the radial scanning, especially when measuring the sphincter dimensions. PMID- 8191856 TI - Helicobacter pylori, the pathologist's point of view. PMID- 8191857 TI - Zygosity diagnosis of twins by questionnaire for twins' mothers. AB - Subjects were 74 twin pairs, 61 MZs and 13 same-sexed DZs who entered the High School affiliated with Tokyo University, Japan. Their mothers also participated. The twins' zygosity was previously identified by many genetic markers. This study aimed at clarifying the effectiveness of zygosity diagnosis by questionnaires distributed to twins' mothers. The questionnaire consisted of three questions concerning the degree of similarity of twins at one year of age; whether they were confused, and if so, by whom. It was slightly modified from that reported earlier by Ooki et al [11] for twins themselves. According to the degree of similarity of the twins, points were allotted thus: from 1 to 3 points for answers to questions (1) and (2) and from 1 to 4 points for answers to questions (3). The sum of the points was calculated, then ranged from 3 to 10. Zygosity was determined by the sum of these points. If the sum was 3-6, the twin pairs were considered MZ and if the sum was 7-10 DZ. It was revealed that more than 90% of twins were identified correctly as MZ or DZ by applying this cutting point and this result was in accordance with that obtained by use of discriminant function analysis. Moreover, the accuracy of the mothers' responses was nearly the same as that obtained by the questionnaire for twins themselves. It was concluded, therefore, that the information from twins' mothers is as correct as that from twins themselves. This questionnaire is simple, practical and especially useful when twins are still too young to participate personally. PMID- 8191858 TI - Size for gestational age and neonatal sleep variables: behavioral indices of risk in fullterm twins. AB - Neonatal sleep behaviors and behavioral state cycling were observed for 20 pairs of same-sex, fullterm twins in which one twin of the pair was appropriate-for gestational-age (AGA) and the other twin was small-for-gestational-age (SGA). Time-sampling recordings were made in active sleep of number and vigor of limb movements, body and head movements, and mouth movements. No group differences were observed for time spent in first active sleep, first quiet sleep, or length of first sleep cycle. Examination of specific behaviors indicated a significantly higher incidence of vigorous limb movements and right hand-to-mouth movements, with a trend for more small limb movements and left hand-to-face movements, for AGA twins when compared with SGA twins. SGA twins had significantly more spontaneous smiles and a trend for spontaneous startles than AGA twins. A stepwise discriminant analysis indicated that a composite of the variables smile, large limb movement, startle, and left hand-to-face significantly discriminated between the two groups, with 90% correct classification of the AGA twins and 75% correct classification of the SGA twins. The results demonstrated the utility of evaluating specific sleep behaviors, rather than state cycling only, to describe differences in neonatal sleep characteristics between AGA and SGA twins. PMID- 8191859 TI - Twinning rate in the Muslim population of West Bengal. AB - Total birth records for the Bengalee Muslim population (BMP) and the Bengalee Hindu caste population (BHCP) for the period 1980-1988 were 17,720 and 119,107 respectively. Of these, the number of twin pairs were 363 BMP and 1,229 BHCP. These data were obtained from the registers of the following hospitals: Islamia Hospital, NRS Medical College and Hospitals and RG Kar Medical College and Hospitals, Calcutta and Medinipore Sadar Hospital, West Bengal, India. The twinning rates found were 20.48 and 10.57 per thousand deliveries in the BMP and BHCP respectively. The proportion of twins, 0.02048, in the BMP was significantly higher (Z = 12.38, p < or = 0.01) than that in the BHCP, 0.01057. This finding of a higher twinning rate in the BMP is corroborated by the fact that available data on the Muslim population of Srinagar in Kammu and Kashmir, and Lucknow and Kanpur in Uttar Pradesh show higher twinning rates than the other populations of India. This increased twinning rate may be due to the greater amount of inbreeding in the BMP. PMID- 8191860 TI - Persistent discordant twin growth following IVF-ET. AB - We observed persistent first trimester growth disparity in a twin pregnancy following IVF-ET. The crown-rump length of the two fetuses was substantially different at 7 and 11 weeks and from the 20th week discordant growth was observed by intertwin differences in abdominal circumferences and estimated fetal weights. Birth weight discordance was 26.6% (1600/2180). This is apparently the first documentation of first trimester growth discordance persisting throughout pregnancy. PMID- 8191861 TI - The use of microsatellites in zygosity diagnosis of twins. AB - Although numerous genetic and anthropological markers are available for determining zygosity of twins, there is still a need for a more practical and informative method in zygosity diagnosis. Dinucleotide repeats or other short repeats (microsatellites) are highly variable between individuals and offer a simple, fast, cheap, and exact approach for zygosity determination. The feasibility of a set of microsatellites to be used for this purpose is demonstrated. PMID- 8191862 TI - A case-control study of maternal gestational weight gain and newborn birthweight and birthlength in twin pregnancies complicated by preeclampsia. AB - To evaluate the influence of rate of gestational weight gain on newborn birthweight and birthlength in twin gestations complicated by preeclampsia, 74 cases of preeclampsia in twin pregnancy were matched to 148 non-preeclamptic twin controls for maternal race, height, pregravid weight, age and length of gestation. Total weight gain was significantly higher for all cases versus controls and for mild cases versus controls. However, the rate of early weight gain was lower for severe cases and severe cases with thrombocytopenia compared to their controls. Mean birthweight and birthlength did not differ between cases and controls, although the proportion with birthlength below the 10th percentile was significantly higher among cases than controls. In addition, the proportion of birthweights and birthlengths < 10th percentile was significantly higher among cases than controls. These findings suggest that inadequate early weight gain in twin gestations complicated by preeclampsia results in retarded birthlength and birthweight. The implication of these findings are discussed. PMID- 8191863 TI - Cytotoxic human lymphocytes: from in vitro testing (1970s) to immunotherapy (1990s). AB - The senior author was the recipient of a contract (1-CP3-3292) from the National Cancer Institute, USA (NCI) in the early 1970s. The aim of NCI's targeted research program was the establishment of a tumour-specific human lymphocyte mediated cytotoxicity assay. Neither lymphocyte growth factors nor monoclonal antibodies for lymphocyte typing were available. Tumour-specific populations of lymphocytes could not be maintained but their presence in ficoll-hypaque preparations of blood buffy coats or in primary cultures of tumours was clearly recognized. Another indiscriminately cytotoxic population of lymphocytes had usually overridden the tumour-specific population. In contradistinction to the ruling doctrine of the era, indiscriminately cytotoxic lymphocytes were readily found in the blood of tumour-bearing patients and healthy individuals (the senior author's lymphocytes were shown to practice indiscriminate cytotoxicity in 1971, an observation first interpreted as "immune surveillance at work" in an individual daily exposed to patients with metastatic cancers). Instead of converting the subject matter of the contract from a tumour-specific to a non specific cytotoxicity assay, the NCI prematurely "phased it out" (but continued the project as intramural research). Nevertheless, many functions of cytotoxic lymphocytes that had become by now well established were foreshadowed during the early 1970s with the limited support of that NCI contract and funds from other sources. Here we recount those early observations; present the outlines of adoptive immunotherapy with various autologous lymphocyte populations and in a separate report in this volume give a technical description how these lymphocyte populations are prepared in the laboratory for therapeutic reinfusions into the patient. PMID- 8191864 TI - A comparative study on growth in soft-agar, adherence to glass and haemolysis types of coagulase-negative staphylococci. AB - Growth properties of coagulase-negative staphylococci in the presence and in the absence of human and rabbit serum in soft-agar prepared in modified Staphylococcus 110 broth were studied. The adherent growth was examined in modified Staphylococcus 110 broth and 1% glucose-meat broth. Of 100 strains examined 69% exhibited diffuse, 18% compact, 7% transient and 6% mixed growth. Compact type colonies were mainly characteristic of Staphylococcus haemolyticus strains. The presence of serum failed to influence the types of colony morphology in any of the strains. Sixty-three percent of the strains showed adherent growth; none of the S. haemolyticus strains produced adherent growth. The glucose-meat broth, unlike modified Staphylococcus 110 broth, was suitable to study adherence. The coincidence of the compact colony morphology in soft-agar and the absence of adherent growth seems to be a taxonomic sign for the species S. haemolyticus and differentiate it from the species Staphylococcus epidermidis. PMID- 8191865 TI - Monocytotoxic antibodies in HIV-infected persons. TNF-alpha treatment of U937 cells increases the complement dependent cytotoxicity. AB - Sera of 40 intravenous drug addicts were tested for the presence of cytotoxic antibodies against uninfected and HIV-infected monocytic U937 cells. Twelve out of 31 seropositive samples proved to be cytotoxic for HIV-infected, untreated target cells in the presence of complement. The TNF-alpha treatment of HIV infected U937 cells increased the detectability of cytotoxic effect of sera (21/31). The complement dependent cytotoxic activity of sera was reduced by pretreatment with recombinant HIV gp120. This reduction proved to be dose dependent in the majority of cases. Immunofluorescence studies indicated that the cytotoxic sera interacted with antigens mostly localized on the cell membrane of HIV-infected TNF-alpha treated U937 cells. The specificity, the possible role and origin of monocytotoxic antibodies in HIV-infected persons is discussed. PMID- 8191866 TI - Carriage, transfer and interaction of oral viruses and bacteria. AB - Carriage of antigens and infectious herpes simplex virus type 1 (HSV-1) and human adenovirus type 1 (Ad-1) by salivary leukocytes was compared with the antibacterial activity of oral polymorphonuclear leukocytes (PMNL) and with the spectrum of oral bacterial and fungal flora. Risk of iatrogenic infections by microbes was assessed by detecting these viruses and microbes after disinfecting dental instruments. The results indicate carriage of antigens and infectious viruses in each age group between 6 and 60 years. Phagocytic activity by PMNL of virus carrier persons was found to be decreased as compared to virus-free subjects. The species number and survival after disinfection of oral bacteria and fungi were significantly higher in virus carrier persons. Infectious viruses were also obtained after disinfecting instruments used in their dental treatment. It is concluded that, virus infection of immune cells can contribute to the oral suppression of phagocytosis by PMNL. Intracellular viruses hidden from disinfectants can also result in infection of other subjects, especially if contemporary immunosuppression exists. PMID- 8191868 TI - Quality assurance in clinical bacteriology--a continuous development in Hungary since 1927. AB - In Hungary, uniform methods and quality assessment date back as early as 1927, when the National Institute of Hygiene and regional public health laboratories were established. The National Microbiology Committee organized in 1984 was replaced in 1992 by the National Clinical Microbiology Board and the Joint Quality Assurance Committee of Clinical Microbiology for which the National Institute of Hygiene acts as an operating centre. A long-range programme of proficiency testing and on-site inspections had a beneficial effect on performance in public health laboratories: in 1989 20 out of 24 of them were scored in the excellent or good degree. Hospital laboratories, which joined this programme only in 1984, exhibited less satisfactory results. PMID- 8191867 TI - Computerized complex typing of Escherichia coli strains from different clinical materials. AB - A multivariate analysis of 3334 Escherichia coli strains originating from different clinical materials revealed that 50.2% of isolates belonged to the most common 12 (O1, O2, O4, O6, O7, O8, O15, O18, O45, O75, O78, O83) out of 133 serogroups. Haemolysin (Hly) production, mannose resistant haemagglutinating activity for human erythrocytes (MRHA) and colicinogenicity (Col) were recorded in 30, 30 and 36%, respectively. Antigens K1 and K5 were present in 11% and 6.6%, respectively. Association were found among certain serotypes and virulence markers (O1, H-, H7, K1, MRHA, Col; O2, H-, Kl, Col; O4, H-, H5, MRHA, Hly; O6, H , H1, MRHA, Hly; O6, K5, MRHA, Col; O7, H-, H4, K1, MRHA, Col; O18ac, H7, K1, Col; O18ac, H-, K5, MRHA, Hly; O78, H-, Col (V-type); O83, H-, K1, Col). There were associations among clinical specimens, age of patients, nosocomial group of diseases, serogroups and virulence markers, too (cerebrospinal fluid-CSF-O7, O18ac, O45, O83-K1-newborn meningitis; O78-ColV-meningitis, sepsis, inflammations diseases of premature babies; CFS-O6, MRHA, Hly-adult-meningitis, sepsis, urinary tract infection-UTI-, pneumonia, other inflammatory diseases; blood-O2, O4, O6, O18ac, ONT, K5, MRHA, Hly-sepsis, UTI, hepatic diseases; urine-O1, O2, O4, O6, O18ac, O75, virulence markers fall to differ among upper and lower UTI; faeces O1, O4, O6, O18ac, O78, virulence markers rare). Associations were also found among animal pathogenicity tests, specimens, serogroups and virulence factors: highly virulent group strains (i.e. LD50 below 10(6)) belonged to serogroups O2, O6, O18ac, possessed antigen K1 (less frequently the presence of MRHA, Hly, K5) and originated mainly from CSF. With mouse lung toxicity test correlations of serogroups (O4, O6, O18ac), antigen K5, MRHA, Hly and specimens (blood) were also shown. However, association was found between the lack of virulence factors and phage insensitivity and also between K5 positivity and sensitivity to phages 16, 17, there were no correlations between serogroups and phage patterns. On the basis of the above-described associations one can find correlations among virulence markers, serotype, and nosological group of diseases. Animal pathogenicity tests give additional data in understanding the pathomechanism of diseases. Correlations between phage patterns and serogroups reveal certain epidemiological relatedness and also virulence of strains. PMID- 8191869 TI - Modifying effects of the parent and radio-detoxified endotoxins on cell-mediated cytotoxicity and cytokine release. AB - The cytotoxic effects of the parent and radio-detoxified lipopolysaccharides (LPS and RD-LPS, respectively) were studied at various concentrations (0-50 micrograms/ml) upon cultured human lung carcinoma target cells. There was no significant difference between the effects of the two endotoxins. LPS and RD-LPS at the same concentrations, however, modified the cytolytic activity of human leukocytes (effector cells) and their mediators in different extent. The most remarkable difference was found at 10 micrograms/ml. A much higher cytotoxic activity of effector cells was observed in the case of RD-LPS as compared to the parent LPS. This concentration used for the treatment of X-irradiated and unexposed effector cells at 24 h incubation resulted in elevated release of some cytokines as measured by ELISA. For increasing the natural defence, RD-LPS as immunomodulator may be of practical value. PMID- 8191870 TI - Comparison of two Salmonella enteritidis phage typing methods. AB - In the last 10 years several phage typing methods were developed for Salmonella enteritidis, leading to confusion in the predominant phage types (PT) reported from different countries. We made comparative examinations on 1487 S. enteritidis strains isolated in Hungary in 1990-1991, using two phage-sets: a modified version of the method elaborated by Laszlo et al. (here in after Hungarian method) and the system of Ward et al. (here in after Colindale method). Typability of the strains was nearly the same: 98.0% and 98.3%, the isolates belonging to 18 and 19 phage types, respectively. The Hungarian method revealed 6 (1, 1c, 1b, 1d, 7, 18), the Colindale method 5 (1, 6, 8, 21, 26) frequent phage types. In Hungary PT 1 has been predominant since 1981 and using the Colindale method 64% belonged to this type; using the modified Hungarian method this type could be divided into PT 1, PT 1c, PT 1b and PT 1d. Other frequent phage types (PT 18, PT 7) were nearly identical with Colindale types PT 26 and PT 21. PMID- 8191871 TI - Acetylator polymorphism in multiple sclerosis. AB - To elucidate whether any relationship exists between genetic polymorphic acetylation and the risk for multiple sclerosis (MS), we determined this polymorphism, using sulphamethazine, in 71 patients with definite MS and in 268 age-matched controls. Thirty-seven patients (52.1%) and 151 controls (56.3%) were classified as slow acetylators (not significant difference). No relation was found between acetylator polymorphism and age at onset of disease in MS patient's group. Our results do not support the existence of any relationship between acetylator polymorphism and the risk for MS. PMID- 8191872 TI - Eye movement quantitative evaluation before and after high-dose 6 methylprednisolone in multiple sclerosis. AB - We studied saccadic and smooth pursuit eye movements in 24 patients suffering from multiple sclerosis during disease worsening, before and after high-dose 6 methylprednisolone infusions. Quantitative evaluation of saccades was based on amplitude/duration and amplitude/peak velocity relationships, precision (i.e. the ratio of actual to desired saccade amplitude) and the latency, whereas smooth pursuit eye movements were studied using target velocity/performance index relationship. At basal recordings, 22/24 (91.7%) of the patients showed at lest one abnormality. Eleven of the 24 patients (45.8%) showed modification of one or several parameters: improvement in 6 patients, worsening in 2, coexistence of both trends in 3. Latency improvement was the only significant modification when patients were considered as a group. Neurophysiological modifications did not correspond to clinical changes. PMID- 8191873 TI - Neurologic complications of anorexia nervosa. AB - The records of 100 patients with anorexia nervosa were reviewed. Neurologic complications were present in 47 patients. Neuromuscular abnormalities were most common and were present in 45% of patients. Generalized muscle weakness was detected in 43% of patients and peripheral neuropathies in 13%. Less common neurologic complications included headaches (6%), seizures (5%), syncope in the absence of orthostatic hypotension (4%), diplopia (4%), and movement disorders (2%). Neurologic problems due to chronic deficiency diseases were rare; only one patient had symptoms directly attributable to a vitamin B12 deficiency and none had evidence of Wernicke's encephalopathy. In most patients, the neurologic complications were reversed completely after correction of nutritional deficiencies and fluid and electrolyte imbalances. PMID- 8191874 TI - Selective techniques of apheresis in polyneuropathy associated with monoclonal gammopathy of undetermined significance. AB - Three cases affected by peripheral neuropathy associated to monoclonal gammopathy of undetermined significance (MGUS) were treated by using selective apheretic techniques, chosen on the basis of the serological characteristics of the gammopathy. Double filtration plasmapheresis was used in the first two cases, respectively affected by gammopathy of IgM type, kappa chains, and IgG type, lambda chains; protein A immunoadsorption in Case 3 with IgG type, lambda chains. Apheretic sessions were performed for three-four months, in association with low dose immunosuppressive therapy. Clear and stable improvement of the neuropathy over 12-month follow-up period was observed both from a clinical and electrophysiological point of view. It is concluded that in peripheral neuropathy associated with MGUS selective techniques of apheresis can prove useful both in obtaining positive results and in avoiding the collateral effect of the original plasma exchange. PMID- 8191875 TI - Inclusion body myositis: clinical, morphological, physiological and laboratory findings in 18 cases. AB - Eighteen consecutive patients with inclusion body myositis (IBM) were studied. The mean age of onset of symptoms was 60 years. A typical clinical pattern with insidious onset of muscle weakness in knee extensors and finger flexors combined with dysphagia was observed. Serial measurements of the maximal voluntary muscle strength revealed a mean loss of muscle strength of 1.4% per month. Two of the cases had common variable immunodeficiency, and three cases had reduced levels of the IgG3 subclass. Treatment with prednisone resulted in a temporary improvement of muscle function in three patients. No positive effect of azathioprine or cyclosporine A could be documented. The results show that IBM may be associated with immunodeficiency, and that prednisone treatment may temporarily improve the clinical signs. The results from our studies on the progression of the muscle weakness may provide basis for future studies on treatment of IBM. PMID- 8191876 TI - Verbal and spatial memory spans in Alzheimer's and multi-infarct dementia. AB - This study aimed to explore verbal and spatial memory spans in Alzheimer's (AD) and multi-infarct (MID) demented patients. For this purpose, we administered the forward and backward versions of the Digit Span and of the Corsi test to 18 AD, 18 MID and 26 controls. Results revealed a normal forward verbal span but reduced backward verbal and forward and backward spatial spans in both demented groups. These data are discussed in the light of the Working Memory model. It is argued that the normal verbal forward span is sustained by a normally functioning Articulatory Loop. The deficient processing resources of the Central Executive, on the other side, are responsible for the reduced extension of the other memory spans. The possible anatomical substrate of short-term memory impairment in dementia, as well as alternative interpretations of memory span performance in demented patients are discussed. PMID- 8191877 TI - Sequelae one year after meningococcal disease. AB - Of 99 consecutive patients with meningococcal disease, 6 died during the acute stage. The 93 survivors were examined one year after hospitalization. 21 (40%) of the adults and 6 (15%) of the children had definite sequelae, and an additional 27% and 11% possible sequelae. 6 adults (12%) and 1 child (2%) had definite neurological sequelae. Electroencephalography (EEG) abnormalities were observed in 7 adults (14%) and 2 children (5%). Epileptogenic activity was present in 3 of these, but none had experienced seizures. 8 adults (19%) and 5 children (14%) had sensorineural hearing loss or impaired vestibular function. Cerebral computerized tomography (CT) scan showed definite and possible abnormalities in 1 (3%) and 6 (18%), respectively, of the 34 patients tested. Neuropsychological tests were performed in 9 patients, 2 of these showed definite impairment. The frequency of neurological abnormalities was higher than in many previous studies, probably reflecting the more comprehensive examinations performed in the present study. However, only 3 patients had serious sequelae. The results suggest that the occurrence of sequelae after meningococcal disease is related to the severity of the acute disease. This may explain the higher rate of sequelae in adults, who have a higher proportion of seriously ill patients. The presence of meningitis is not required for the occurrence of neurological sequelae. PMID- 8191879 TI - mRNA expression of neurotrophins and members of the trk family in the rat brain after treatment with L-deprenyl. PMID- 8191878 TI - Sneddon's syndrome (livedo reticularis and cerebrovascular lesions) with antiphospholipid antibodies and severe dementia in young man: a case report. AB - We present the case of 37-year-old man with Sneddon's syndrome and antiphospholipid antibodies. His chief neurological manifestation was rapidly progressive dementia, which developed 6 years after the appearance of livedo reticularis. PMID- 8191880 TI - Concentration of endogenous ethanol in blood and CSF. PMID- 8191881 TI - Effects of phenytoin and carbamazepine on cognitive functions in newly diagnosed epileptic patients. AB - Phenytoin (PT) and carbamazepine (CBZ) are the two most prescribed anticonvulsants in Finland. Their effect on the cognitive functions of 43 newly diagnosed epileptic patients was examined. The medication was randomly assigned. The patients were tested before the medication was started, and after half a year's therapy. In order to estimate the practice effect in repeated testing a control group of 21 volunteers was similarly tested and retested. Both anticonvulsants, PT in particular, decrease the normal practice effect observed in neuropsychological testing. Compared to the CBZ group, patients with PT became somewhat slower, and their visual memory decreased. Within the PT group the motor slowing was more marked in female patients, and in patients having higher PT serum levels. In PT and CBZ groups there was an equal decrease in negative mood i.e. tension, depression, bewilderment and irritability. PMID- 8191882 TI - Neuro-ophthalmic manifestations of the syndrome of ophthalmoplegia, ataxia and areflexia. Observations on 20 patients. AB - The neuro-ophthalmological manifestations of 20 patients with the syndrome of ophthalmoplegia, ataxia and areflexia are described. The symmetrical nature of the ophthalmoplegia and the associated cerebellar ataxia point to centrally placed lesions. Several supranuclear, nuclear and internuclear ophthalmological signs are identified. Some of these, like partial sparing of the levator palpebrae and normal downgaze in the presence of severe ophthalmoplegia are noted too frequently to be just unusual signs of peripheral oculomotor dysfunction. Other identified features included upper lid retraction on attempted upgaze and preserved Bell's phenomenon in the presence of paralysis of the latter, as well as several other central ophthalmological signs. These findings contrast with those seen in the Guillain-Barre syndrome and, thus, the syndrome of ophthalmoplegia, ataxia and areflexia is not a mere variant of it. PMID- 8191883 TI - Effect of high-dose steroid therapy on T-cell subpopulations. A longitudinal study in MS patients. AB - Lymphocyte subpopulations, T cell activation antigens, and serum levels of interleukin 2 (IL-2) and soluble IL-2 receptor (sIL2R), were studied in relapsing remitting MS (RR-MS) patients before and after high-dose steroid therapy. Prior to therapy, a minority of patients showed increased HLA-DR antigen expression, and an increased number of CD16+ and CD19+ cells. Steroid treatment induced a significant increase in HLA-DR and CD19 expression, a significant reduction in CD16+, CD57+, and CD8+ CD57+ cells, and a slight, non-significant, decrease in IL 2 and sIL-2R levels and CD25 expression on CD4+ T lymphocytes. PMID- 8191884 TI - Temporal bone dynamics, the hard way. Formation, growth, modeling, repair and quantum type bone remodeling in the otic capsule. AB - This review presents studies in which temporal bone dynamics were monitored in undecalcified human and animal materials by combined microradiography and osteofluorochromic time labeling. The results are interpreted in accordance with modern concepts of spatial and temporal organization of bone behavior in an attempt to contribute to a new basis for understanding the structure and function of the bony otic capsule. In postcartilaginous development, perilabyrinthine bone formed a separate functional unit in which growth and modeling were absent. Consequently, all drift movements bypassed the bone present inside a narrow perilabyrinthine zone, which in effect maintained a so-called drift barrier enclosing the entire inner ear. In baseline bone remodeling and repair-associated remodeling transients, secondary osteons were distributed centrifugally with respect to inner ear spaces, and the average osteonal size decreased towards the inner ear, suggesting a progressive inhibition of bone resorption towards inner ear spaces. No histological capsular component proved resistant to bone resorption during modeling and remodeling. Instead the dynamic behaviour of any moiety of capsular bone appeared to depend on its spatial relation to the membranous labyrinth rather than on histological characteristics. This spatial organization of perilabyrinthine bone development and turnover is responsible for the unique histology of capsular bone and may explain the accumulation of fatigue micro-cracks which can be found in human perila byrinthine bone. These findings suggests the role of inner ear tissues as a functional matrix in control of capsular bone dynamics even beyond fetal life. PMID- 8191885 TI - Magnetic resonance examination of the inner ear and cerebellopontine angle in patients with vertigo and/or abnormal findings at vestibular testing. AB - The inner ears of 167 patients with vertigo and/or abnormal findings at vestibular testing were studied using magnetic resonance (MR). Pathology potentially explaining vertigo was found in 54 patients, and was detected in the posterior fossa (28%), the internal auditory canal (28%) and the membranous labyrinth (44%). The overall percentage of pathology and the percentage of pathology found in the membranous labyrinth was high and was probably influenced by the referral pattern in our hospital where high resolution MR of the inner ear (three dimensional Fourier transformation-constructive interference in steady state sequence; 3DFT-CISS sequence) is available. Unenhanced, and especially gadolinium (Gd)-enhanced T1-weighted spin-echo images, are needed to detect most of the pathology inside the internal auditory canal, and some of the lesions inside the membranous labyrinth. 3DFT-CISS images are the only images that can show fibrous obliteration of the intralabyrinthine fluid spaces, and are therefore necessary to recognise most of the intralabyrinthine pathology. Finally, T2-weighted spin-echo images are best suited to demonstrate cerebellar or brain stem infarction. An additional MR-angiography sequence (three dimensional Fourier transformation-fast imaging with steady precession; 3DFT FISP) is used when vascular compression of the cochleovestibular nerve is suspected. MR is the method of choice to look for pathology in patients with vertigo, and allows detection of pathology that remains invisible with other imaging techniques. However, well adapted sequences are needed to detect these lesions. PMID- 8191886 TI - Vestibular compensation. AB - Regulation of the human equilibrium differs from the other, mostly linear, human senses. It consists of a multitude of receptors and an interrelated network that is necessary for data processing as well as for regulatory processes. Thus, the human equilibrium system represents a mixture of hardware and related software interactions. The input is also named the "equilibrium tetrade" (1-3), and comprises vision, vestibular inertia acceleration perception, proprioception and hearing. In the case of various types of lesion, one has to deal with a variety of morphological as well as mostly functional reparations. Amongst others these consist of restitution, adaptation, suppression, habituation and compensation. In order to objectively investigate the type of ongoing compensatory reparation within the complex network functions of the equilibrium system, we need to apply the so-called complex vestibular equilibrium tests. These allow us to quantitatively check for the response outputs after varying stimulus loadings, as well as after spatial or temporal stimulus interferences. For testing the equilibrium system under the condition of varying stimulus intensity impacts, the vestibular stimulus response intensity comparison test (VSRIC) is applied (4-6). Spatial stimulus interference between the ocular and the vestibular system is checked by means of the calorisation pendulum interference test (CPIT) (1, 2, 5, 7-9). In the case of temporal stimulus interference testing it is assumed that a memory copy of earlier stimuli influences successive reactions. Thus phenomena such as learning or habituation can be induced. Temporal stimulus interference is tested by means of the caloric adaptation cyclogram (CAC) (2-5, 10, 11). PMID- 8191887 TI - Surgery for non-Meniere's vertigo. AB - Neurootologists are fortunate in having a considerable number of surgical options available to them for the treatment of patients with disabling vertigo. Most surgery for vertigo is performed on patients suffering from the ravages of Meniere's disease. In addition, other forms of disabling peripheral vertigo may also be surgically managed. Over a 3 year period, the author performed surgery on 14 patients suffering from disabling non-Meniere's vertigo. During the same period, 60 patients with Meniere's disease underwent surgical treatment. There were three non-Meniere's conditions for which surgery was performed: chronic vestibular neuronitis, delayed onset vertigo (after sensorineural hearing loss), and labyrinthine injury following temporal bone fracture. Two surgical operations were utilized: transmastoid labyrinthectomy and selective vestibular neurectomy. At 1 year follow-up all of the patients involved in this study enjoyed either total relief of symptoms or marked improvement, demonstrating that satisfactory surgical results can be obtained for non-Meniere's vertigo. However, surgeons must exercise extreme caution in selecting non-Meniere's patients for surgery. Moreover, proper patient selection, accurate diagnosis and the exclusion of central disease are crucial in obtaining good surgical results. PMID- 8191888 TI - Recovery from unilateral vestibular nerve section in human subjects evaluated by physiological, psychological and questionnaire assessments. AB - Patients undergoing vestibular nerve section for vertigo or acoustic neuroma surgery were compared pre- and post-operatively and during long-term follow-up using a range of tests including: nystagmography, impulsive rotational testing of the vestibulo-ocular reflex (VOR), ability to estimate and reproduce imposed rotational displacements, validated questionnaires rating vertigo, imbalance, autonomic reactivity and somatisation, and clinical and self-assessment scales of overall outcome in terms of symptoms and disability. Correlations were found between rating scale assessments, questionnaire scores and estimates of self rotation. Neither nystagmography nor VOR tests correlated with the presence or severity of vertigo or imbalance. Post-operatively, vertigo patients reported that they had received significant relief, although they had higher incidences of residual complaints of imbalance and vertigo than patients after acoustic neuroma surgery. Factors impeding rehabilitation in patients with vertigo are discussed. PMID- 8191889 TI - Physiopathology of peripheral non-Meniere's vestibular disorders. AB - This paper reviews the physiopathological basis of some labyrinthine or vestibular nerve disorders illustrating a particular mode of vestibular dysfunction. The discovery of the physiopathology of these disorders has relied on neuroanatomical data, histopathological observations of human temporal bones, historical principles of vestibular physiology, surgical exploration, blood testing which provides indirect evidence of immune or metabolic disorders, and results from animal experiments. While all data are valid, advances in sensory cell physiology, development of new vestibular tests, and progress in imaging techniques are necessary in order for a better understanding of the mechanisms involved in vestibular end organ dysfunction to be obtained. PMID- 8191890 TI - The contractile and electrophysiological effects of rolipram in guinea-pig papillary muscles and isolated ventricular myocytes. AB - Isometric force, action potentials and in voltage-clamp Isi (second inward current) and its current voltage relation were recorded in papillary muscles from guinea-pigs and from guinea-pig isolated ventricular myocytes (35-37 degrees C, 0.5-1 Hz). Rolipram (1-100 microM) had no significant effect on peak isometric twitch. The rate of rise of force and time to peak tension (TPT) was likewise unaffected. Time to half relaxation (THR) was increased in a dose-dependent manner and at 30 microM THR was prolonged by 25.3 +/- 6% (n = 10, P < 0.001). The effect of 30 microM rolipram on isometric force was frequency dependent. At 0.25 Hz peak force was increased by 6.3 +/- 3.1% (n = 7, P < 0.05). At 2 Hz rolipram exhibited a negative inotropic effect of 9.8 +/- 3.3% (n = 5, P < 0.02). Action potential duration at 90% repolarization was prolonged by 13 +/- 6 ms (n = 7, P < 0.05), and there was usually no effect on resting potential or action potential amplitude. Sometimes, however, a depressed plateau was recorded. Rolipram was without effect on Isi and its current-voltage relations. Time to full mechanical restitution after a test interval was not changed but the shape of the restitution curve was altered. The restitution process was much slower in the presence of rolipram. Hence, peak force was lower at test intervals shorter than 800 ms. Likewise, the shape of the curve relating postextrasystolic potentiation to test interval was altered by rolipram.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191891 TI - Mechanical and electrophysiological effects of milrinone on the force-frequency relationship in mammalian myocardium. AB - Isometric force, action potential and current-voltage relation were studied in guinea-pig and ferret papillary muscles. Milrinone (1 microM) increased peak twitch force by 40 +/- 4%, reduced time to peak tension (TPT) by 12.1 +/- 3% (n = 6, P < 0.01) and reduced time to half relaxation by 17.3 +/- 4.1% (n = 6, P < 0.01). The effect of milrinone was potentiated by rolipram, a RI-PDE inhibitor which in itself had no inotropic effect. After the addition of rolipram peak isometric force was increased by 104 +/- 8% (n = 6, P < 0.001), TPT was further reduced whereas time to half relaxation was slightly increased after the addition of rolipram. Action potential duration at 75% repolarization was decreased by 11 +/- 5 ms (n = 6, P < 0.05). Milrinone also potentiated the second inward current (Isi) by 21 +/- 3.2% (n = 6, P < 0.01). Peak twitch force in response to a test stimulus after an interval, i.e. mechanical restitution was increased at all intervals. The onset of restitution was faster and time to full restitution also shortened. Maximum postextrasystolic potentiation was greater in the presence of milrinone, whereas relative potentiation was smaller in presence of milrinone (46 +/- 7%) than in control (74 +/- 7%). The recirculation fraction of activator calcium was enhanced by milrinone from 0.35 +/- 0.04 to 0.48 +/- 0.07. The results support the view that the positive inotropic effect of milrinone is due to a greater inflow of calcium during the action potential and a more efficient intracellular calcium handling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191892 TI - Dynamic changes of myocardial inositoltrisphosphate and cyclic nucleotides: relationship to contractile response in the perfused working rat heart after adrenergic and muscarinic agonist stimulation. AB - Initial and late effects by adrenergic and muscarinic agonists on inositol trisphosphate (IP3) and cyclic nucleotide levels were determined and correlated to mechanical response in perfused rat hearts. Forty-three rat hearts were perfused with Krebs-Henseleit buffer in a modified Langendorff apparatus as a working preparation. The hearts were perfused as controls (n = 11), or with noradrenaline (10(-6) mol l-1) (n = 21), or with carbachol (3 x 10(-7) mol l-1) (n = 11) added to the perfusion buffer. The hearts were frozen at 20 s, 30 s and 40 min after addition of noradrenaline and at 20 s and 40 min after addition of carbachol, and after 5 and 45 min of control perfusion. cAMP and cGMP were determined by radioligand methods and IP3 by a combined fast performance liquid chromatography (FPLC)-isotachophoretic method. cAMP increased by 36% within 20 s followed by a decrease (22%) during the 10 s following noradrenaline addition. After 40 min cAMP regained its value near that of 20 s. Noradrenaline perfusion did not influence IP3 levels during the first 30 s although the value at 40 min was significantly higher (59%). IP3 increased (42%) after 20 s of carbachol perfusion followed by a 25% decrease at 40 min. Sustained stimulation of beta receptors (after 40 min in our model) resulted in a repeated increase in cAMP only, without an increase in contractility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191893 TI - The effect of exercise on the contractile properties of single skinned fast- and slow-twitch skeletal muscle fibres from the adult rat. AB - The effects of long-term endurance exercise on the contractile properties of single skinned muscle fibres from adult rats, were investigated. Adult (4-month old) male rats were subjected to a 16-week, high-intensity endurance swimming programme, where animals carried a load (corresponding to 2% of body wt), during all 2-h training sessions. At the conclusion of the training period, muscle fibres isolated from the extensor digitorum longus (EDL), and soleus (SOL), could be classified into distinct classes or fibre types on the basis of their Ca(2+)- and Sr(2+)-activated contractile characteristics. The fast-twitch EDL comprised two fibre populations, while the slow-twitch SOL was found to be composed of three distinct fibre types. Endurance swimming modified the contractile characteristics of fibres from both the EDL and SOL, but exerted greater influence on those of the SOL. This was illustrated by significant increases in the sensitivity to Ca2+ and Sr2+, and a lower threshold for contraction by these activating ions, in the exercised group. Not one of the total of 272 fibres sampled, exhibited mixed fast- and slow-twitch contractile characteristics, often associated with exercise-induced fibre type transformations. Thus, high-intensity endurance swimming induced changes in some single muscle fibre contractile properties of adult rats, but did not cause major changes in fibre type distribution. PMID- 8191894 TI - Visco-elastic properties of the rapidly adapting stretch receptor muscle of the crayfish. AB - The visco-elastic properties of the receptor muscle associated with the rapidly adapting stretch receptor organ of crayfish (Pacifastacus Leniusculus) were studied by recording the tension responses to various length changes. Steady state length changes resulted in a non-linear tension development in the receptor muscle. The tension increased slowly for small extensions and more rapidly when extension increased. Muscle tension responses to ramp-and-hold extension were characterized by a transient peak followed by a gradual non-exponentional decline in tension. At the onset of the ramp the tension increased rapidly, similar to what has been observed in the muscle of the slowly adapting receptor (SM). The steeper rise in tension during the first part of the ramp indicating higher initial stiffness, resulted in a 'hump' when large extensions (> 15%) were applied. The results show that the rapidly adapting receptor muscle has a more pronounced dynamic component; the ratio between the amplitude of the peak and the steady state response was larger in the rapidly than in the slowly adapting receptor muscle. Accordingly, different values for the elements of a visco elastic model of the muscle had to be set for the two types of receptors. The different properties of the rapidly and slowly adapting receptor muscles are in line with the differences in the overall adaptive behaviour of the organ and give further support to the idea that mechanical factors contribute to the adaptive properties. PMID- 8191895 TI - Rhythmic contractions in isolated small arteries of rat: role of K+ channels and the Na+,K(+)-pump. AB - Small mesenteric arteries from Wistar rats display rhythmic tension oscillations, associated with oscillations in membrane potential, when stimulated with noradrenaline. The purpose of this study was to investigate the role of potassium conductance and Na+, K(+)-pump activity in the generation of these oscillations. The effect on the rhythmic contractions of several agents, interacting with K+ channels, was studied. Application of apamin, pinacidil or glibenclamide did not affect the rhythmic activity. Tetraethylammonium (TEA) increased the frequency of the rhythmic contractions, while application of 4-aminopyridine (4-AP) increased the amplitude by approximately 50%, with no changes in frequency. Ba2+, on the other hand, impaired the rhythmic contractions or converted them to irregular oscillations in the presence of functional endothelium, but did not affect oscillations in endothelium-denuded vessels. Ouabain or exposure to K(+)-free solution, procedures known to inhibit the Na+,K(+)-pump, abolished the rhythmic contractions. This effect was immediate, suggesting that it was due to elimination of the electrogenic action of the Na+,K(+)-ATPase, rather than to a change in intracellular ion concentrations. Exposure to an extracellular potassium concentration of more than 20 mM also inhibited the oscillation activity. The results suggest that the oscillations are not caused by, but may be modulated by, variations in potassium conductance. The Na+,K(+)-pump seems to play an important role in the generation of rhythmic contractions in these vessels. PMID- 8191896 TI - Effects of long-term portal hypertension on structure, active force and content of contractile and structural proteins in smooth muscle of the rat portal vein. AB - Growth of the smooth muscle cells in the rat portal vein was induced by a partial ligation of the vessel. The ligation caused an increase in the transmural pressure and segments of the portal vein were investigated 6 weeks after the ligation. The spontaneous contractile activity of the ligated veins was similar to that of the control veins. In the ligated vessels the active force at optimal length for force development was doubled, 22.8 +/- 1.3 compared with 12.5 +/- 1.4 mN for the controls. The cross-sectional area of the media in the ligated veins, determined on transverse sections, increased from the control value of 0.10 +/- 0.01 to 0.19 +/- 0.01 mm2. Electron microscopy revealed that the mean cross sectional area of the smooth muscle cells in the ligated portal vein was doubled (controls: 6.4 +/- 0.6, hypertrophic: 13.6 +/- 1.8 microns2). This suggests hypertrophy of the smooth muscle cells in the vessel wall as the cause for the increase in cross-sectional area of the ligated veins. An increase in the number of intermediate filaments was observed in the hypertrophied smooth muscle. The relative contents of contractile (myosin and actin) and structural (desmin and vimentin) proteins were determined with SDS-polyacrylamide gel electrophoresis. The actin/myosin and vimentin/actin ratios were unaltered by hypertrophy. The hypertrophied veins showed an increase in the desmin/actin ratio (control: 0.20 +/- 0.01, hypertrophied: 0.27 +/- 0.03). The increased amounts of desmin correlates with the increased number of intermediate filaments observed by electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191897 TI - Hypertension and thirst outlasting renal vasoconstriction as effects of a brief evaluation of systemic angiotensin II in sheep. AB - The influence of 10 min intracarotid (i.c.) and intravenous (i.v.) infusions of angiotensin II (Ang II; 20 pmol kg-1 min-1) on carotid blood pressure (cBP) and renal blood flow (RBF) was studied in unanaesthetized ewes without and with pre treatment with the alpha 1- and beta-adrenoceptor blocker labetalol. RBF was also monitored during 30 min intracerebroventricular (ICV) infusions of Ang II at 2 pmol kg-1 min-1. The i.c. infusions of Ang II induced about 50 mmHg rise in cBP. A steep decline occurred during 5 min post-infusion, followed by a much slower reduction with the cBP remaining above control level at 40 min post-infusion. The pressure elevation induced by i.v. Ang II was less pronounced but exhibited a similar pattern. Labetalol significantly reduced the pressor response to i.c. as well as i.v. Ang II. The i.c. and i.v. infusions of Ang II conspicuously reduced the RBF regardless of whether the ewes were labetalol-treated or not. At 5 min after the infusions RBF had returned to control level. The ICV infusions did not influence the RBF. Ang II i.c. elicited thirst in 50% of the ewes with the urge to drink remaining at 40 min post-infusion. The dipsogenic response was not reduced by labetalol pretreatment. The results imply that no cerebral component contributes to the reduction in RBF induced by systemic Ang II. However, a centrally mediated action seems to be the cause of the long-lasting post-infusion cBP elevation and dipsogenic response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191898 TI - Analysis of the pressure-flow characteristics of isolated perfused rat kidneys with inhibited tubular reabsorption. AB - The renal hemodynamics were studied in an isolated perfused rat kidney model modified for investigations of the glomerular permeability characteristics. The tubular reabsorptive activity was inhibited by perfusion at low temperature (8 degrees C) in the presence of furosemide and nitroprusside resulting in a dramatic increase in the filtered load of fluid and solute reaching the tubules and hence in tubular pressure. The glomerular filtration rate (GFR), arterial pressure (PA) and needle pressure (intrarenal tissue pressure, PiR) were continuously recorded and the glomerular hydrostatic pressure was estimated by an arterial occlusion technique. The pre- to postglomerular resistance ratio was calculated from the pressure vs. GFR relationships for two perfusates having differing oncotic pressures (pi = 5.5 and pi = 20 mmHg), from which estimations of glomerular hydrostatic pressures (PGC) were concomitantly made. Thus, increases in delta pi could be exactly counterbalanced by equally large increases in PGC for any given GFR, the needle and Bowman's capsule pressures being dependent on GFR but not on plasma colloid oncotic pressure. The experimental interventions resulted in a pronounced elevation of PiR as compared with in vivo conditions, while the PGC values were in a normal range, resulting in reduced glomerular filtration pressures. Furthermore, the clearance of albumin varied with the oncotic pressure in agreement with the notion of heteroporosity. PMID- 8191899 TI - Reduced permselectivity in isolated perfused rat kidneys following small elevations of glomerular capillary pressure. AB - A modified rat kidney preparation was used to explore how changes in hydrostatic pressure affect the permselective properties of the glomerular capillary bed. The maximally vasodilated kidneys of 18 rats were perfused with albumin solutions (16.7 g l-1) at different flow rates and hence arterial pressures (PA). One kidney in each rat was exposed to pressure elevations with the other kidney serving as a control perfused at constant PA of about 100 mmHg. Both the vascular resistance to flow and the glomerular filtration rate (GFR 34.6 +/- 2.9 ml min-1 100 g-1) were similar in the two kidneys at equal PA and remained constant throughout the experiment. The ratio of albumin clearance over GFR (theta) was initially around 0.4% at constant PA and gradually increased during 1.5 h to reach 0.7% at the end of the experiment. A direct increase of PA from 100 to 200 mmHg for 15 min resulted in a calculated increase of the effective glomerular filtration pressure gradient of 10-15 mmHg and in a two-fold increase of theta when measured at an identical PA of 100 mmHg. Albumin clearance was almost fully normalized within 20 min similar to that observed in e.g. skeletal muscle. However, the glomerular capillary barrier seemed to be far more sensitive to elevations of hydrostatic pressure than other capillary walls which require capillary pressure increments of 60 mmHg in order to induce similar reversible changes in permeability. Therefore, we conclude that an elevated PGC per se induces changes of glomerular permselectivity, which may have important pathophysiological implications during conditions of proteinuria. PMID- 8191900 TI - Serum hormones and strength development during strength training in middle-aged and elderly males and females. AB - Effects of a 12-week progressive strength training period on serum concentrations of testosterone, cortisol and sex-hormone-binding globulin (SHBG) as well as on strength development of the leg extensor muscles were investigated in nine middle aged males (M50; range 44-57 years) and in nine middle-aged females (F50; range 43-54 years) as well as in 10 elderly males (M70; range 64-73 years) and in 11 elderly females (F70; range 66-73 years). Substantial increases took place in maximal isometric strength during the 12-week training period both in M50 (from 2834 +/- 452 to 3941 +/- 772 N; P < 0.001) and in F50 (from 2627 +/- 725 to 3488 +/- 1017 N; P < 0.001) as well as in M70 (from 2591 +/- 736 to 3075 +/- 845 N; P < 0.01) and in F70 (from 1816 +/- 427 to 2483 +/- 408 N; P < 0.001). The relative increases in strength during the 12-week training period did not differ significantly between the groups. However, during the last 4 weeks of the training none of the groups demonstrated further increases in strength but it actually decreased in F50 (P < 0.05), M70 (P < 0.01) and in F70 (P < 0.05). No systematic changes were observed during the training in the mean concentrations of serum total testosterone, free testosterone, cortisol, and SHBG, nor in testosterone/cortisol and testosterone/SHBG ratios. However, the individual levels of serum testosterone and testosterone/cortisol ratio and the individual changes in strength during the last four most intensive training weeks of the 12 week period were in significant positive linear correlation in F70 (r = 0.57; P < 0.05) and in M70 (r = 0.61; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191901 TI - Glucose kinetics during exercise in trained men. AB - Six trained men were studied to examine the relative increases in hepatic glucose output and peripheral glucose uptake during 40 min of exercise at 75% VO2max. Rates of appearance (Ra) and disappearance (Rd) were measured using a primed, continuous intravenous infusion of D-[3-3H]glucose. Plasma glucose increased (P < 0.05) from 4.8 +/- 0.2 mmol l-1 at rest to 6.2 +/- 0.5 mmol l-1 after 40 min of exercise. Both Ra and Rd increased (P < 0.05) during exercise, however, during the early phase of exercise, Ra exceeded Rd (P < 0.05). Ra peaked at 42.0 +/- 3.2 mumol kg-1 min-1 after approximately 15 min of exercise. In contrast, the highest Rd of 33.9 +/- 4.3 mumol kg-1 min-1 was measured at the end of exercise. In additional experiments, five men were studied during 40 min of exercise at 70-75% VO2max, 2 h after ingestion of the non-selective beta-adrenergic antagonist timolol or a placebo capsule. Subjects were unable to complete the exercise bout following timolol, fatiguing after 28.0 +/- 4.0 min (P < 0.05). The increase in blood glucose from 4.3 +/- 0.1 to 4.7 +/- 0.3 mmol l-1 (P < 0.05) following 20 min of exercise under control conditions was completely abolished by prior timolol ingestion (4.2 +/- 0.2 to 4.1 +/- 0.2 mmol l-1). These results demonstrate that during exercise at 75% VO2max in trained men, hepatic glucose output is not always closely matched to peripheral muscle glucose uptake and may be subject to feed-forward regulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191902 TI - Effect of glucose-6-phosphate and pH on glucose transport in skeletal muscle plasma membrane giant vesicles. AB - The effect of glucose-6-phosphate (G-6-P) and pH on glucose transport was studied in skeletal muscle plasma membrane giant vesicles containing GLUT4 but not GLUT1. Vesicles (average diameter 7.6 microns) were obtained by collagenase treatment of muscle. The vesicles were incubated with 10 mmol l-1 G-6-P and, after 0.5 and 2 h of incubation, the intravesicular G-6-P concentration was 0.93 +/- 0.4 mmol l-1 and 1.18 +/- 0.5 mmol l-1 (mean +/- SE, n = 4), respectively. In order to increase the intravesicular G-6-P concentration, 0.001% saponin was added during incubation, which increased the 2-h intravesicular G-6-P concentration to 4.57 +/ 1.0 mmol l-1 (n = 4). Initially, vesicles were used for glucose transport studies after 30 min of incubation with 10 mmol l-1 of G-6-P. There was no effect of G-6-P on either the affinity constant (Km) or maximal velocity (Vmax) of the glucose transport. Subsequently, vesicles were incubated for 2 h with 10 mmol l-1 of G-6-P and 0.001% saponin. Still no effect of G-6-P on glucose transport could be detected. In contrast, the rate of D-glucose transport was affected, when extravesicular pH was varied from 6.0 to 7.8. The maximum glucose transport rate was found at pH 7.2 and was decreased at both higher and lower pH. It is concluded that G-6-P has no effect on GLUT4 intrinsic activity in rat skeletal muscle plasma membrane. In contrast, GLUT4 intrinsic activity is sensitive to changes in pH. PMID- 8191903 TI - [Charcot and psychiatry]. PMID- 8191904 TI - [Gerontology, a problematic science]. PMID- 8191905 TI - [Restructuration of psychiatric care in Latin America]. AB - Both the epidemiological and program bases for action are reviewed as well as the political, historical, and technical background of the Initiative for a Re structuration Psychiatric Care in Latin America. Attention is also paid to (a) the wide repercussion of this new-old health policy, (b) procedures for its implementation, and (c) the main obstacles the Initiative has been facing to date. Results obtained so far are reviewed. PMID- 8191906 TI - [Patterns of drug abuse among youngsters of upper social class]. AB - Street drug use, and alcohol abuse among young adults from a high social class range were studied in the posh seaside resort of Punta del Este (Uruguay) during the (austral) summer vacation (February 1993). In this connection, an anthropological methodology was applied: Four young people were trained in systematic record and observation technics abilities. Results suggest two clearly defined social-cultural patterns with regard to both cannabis, and cocaine use. Both patterns take place within a social environment agreeable to drug use as well as strongly connected with social interaction ways peculiar to high-class youth. PMID- 8191907 TI - [Locus of control: differences by sex and age]. AB - To explore gender-, and age-related differences on locus of control orientation, the Levenson's Tri-factorial Scale was administered to a 1200-male/female Brazilian subjects sample within a 17-to-56 age range. Anova 2X7 found out a main effect due to gender on the "Powerful Others" factor, men scoring higher than women. Reliable age differences were observed at the level of internality factor when scoring for "Total Internality". Generally speaking, internality increased with age. PMID- 8191908 TI - [Space perception in cerebral hemisphere damage. Neuropsychological study]. AB - The present study was aimed at using both semiotic and symbolic spaces as an exploratory method of the simultaneous synthesis, and interhemispherical transfers among hemiplegic patients. Thirty-six hemiplegic patients with an established neurological deficit were selected, then split into two groups: 19 patients with their dominant hemispheres affected, 17 patients with their subordinate hemispheres affected. The following types of patients have been excluded from this study: Patients with cerebral degenerative and/or progressive alterations, patients with sensory aphasias, and damage to the counterlateral side opposite the hemiplegic side. Age range was 67.2 (with 45-year-old as a minimum, and 70-year-old as a maximum). Subjects were 11 females and 25 males. Both the semiotic, and the symbolic spaces have been explored as well as the existence of a parietal, sensitive syndrome, and damage topography by means of a scanner device. A major damage of the symbolic space in patients with their dominant hemispheres affected was observed. Conversely, semiotic space, in its figurative trait, was most affected in patients with their subordinate hemispheres affected. PMID- 8191909 TI - [Drug combinations of lithium: reasons and limitations]. AB - Lithium is widely used in the treatment of several psychiatric diseases-bipolar mood disorder, in particular. It is often necessary to have lithium combined with other psychopharmacological agents when efforts are aimed at either enhancing a less-than-optimal therapeutic effect or treating other symptoms as well. A therapist should be familiar with every possibility, limitation, and probable risk such pharmacological combinations are likely to lead to. PMID- 8191910 TI - [The myth of the saint of the sword]. AB - The authors delve into an Argentine enigma: The character of Gen. Jose de San Martin--a historical figure that has been sacralized as Father of the Homeland, and hailed by historians as a saint with a sword. A short biographical sketch is offered prior to an analysis of Gen. San Martin's psychological traits coupled to his work with masonic lodges that allowed him to display his abilities as strategist and political ruler. The mystery of his giving up his military and political tasks after his meeting with Simon Bolivar in Guayaquil can be compared to an epilogue to the "destiny" of a paradigmatic hero. Such a paradigm unites Gen. San Martin's own traits on the one hand, and a longing for a powerful fatherly image among Latin American communities, on the other hand. San Martin was no saint, no prophet, and no "shrewd half-breed" whose ultimate ambitions fell apart: Instead, he was a stoic revolutionary very much "de son temps"- however, his fellow countrymen simply cannot accept or admit that he was no worshipper or that his were very human qualities, and defects. PMID- 8191911 TI - Changes in erythrocyte deformability in normal pregnancy and pregnancy-induced hypertension, as revealed by electron spin resonance. AB - To study changes in hemorheologic properties during pregnancy, erythrocyte deformability was measured by an electron spin resonance (ESR) method. The results obtained by this method showed that erythrocyte deformability in normal pregnancy decreased significantly in the first trimester compared with nonpregnant controls, and continued to decrease slightly as pregnancy progressed. On the other hand, erythrocyte deformability in severe pregnancy-induced hypertension (PIH) was significantly lower than that in the third trimester of normal pregnancy. Additionally, we found that the hematocrit level needed for erythrocytes to exhibit high deformability is lower during pregnancy. These results suggest that hemodilution in normal pregnancy, so-called hydremia, compensates for the decrease in erythrocyte deformability. Conversely, since erythrocytes become less deformable in a hemoconcentration condition in severe PIH, microcirculatory disturbance of various organs, including the uteroplacental unit, may occur. The lowered erythrocyte deformability may be one of the important pathologic features in PIH. PMID- 8191912 TI - Regulatory effect of lymphokine-activated killer cells on epidermal proliferation induced by cholera toxin in mice. AB - We investigated the effects of lymphokine-activated killer (LAK) cells on epidermal hyperplasia induced by cholera toxin (CT). LAK cells showed cytotoxic activity against both tumor cell lines and proliferating normal cells including skin epidermal cells. When 1 x 10(7) LAK cells were injected intradermally together with 1.0 ng of CT, epidermal hyperplasia was markedly suppressed. The LAK effectors inhibiting epidermal hyperplasia showed surface phenotypes of asialo-GM1+, Thy-1+, Lyt-2- and L3T4-, that were different from those of LAK cells killing tumor cells in vitro. Epidermal hyperplasia induced by CT was not suppressed by topical administration of cytokines such as interleukin-2, interferon and tumor necrosis factor. Therefore, the antiproliferative effect of LAK cells might be attributed to their direct action on the epidermal cells. PMID- 8191913 TI - Administration of a branched-chain amino acid preparation during hepatic failure: a study emphasizing ammonia metabolism. AB - We administered a branched-chain amino acid (BCAA) infusion to 16 patients with hepatic failure and two healthy subjects, and then evaluated its effects on ammonia metabolism and amino acid metabolic pool. Immediately after the BCAA infusion, the venous blood ammonia concentration increased in 12 of 15 patients with hepatic failure and in both two healthy subjects. Glutamine (Gln) also rose in all cases following the BCAA infusion, and this rise was particularly marked in the hepatic failure group. The increase in Gln due to the BCAA infusion and the arteriovenous difference in the pre-administration ammonia concentration showed a good correlation. These results suggest an increase in glutamine cycle capacity in patients with hepatic failure. PMID- 8191914 TI - An experimental hemodynamic study of the pelvic collateral circulation. AB - Iliac arteries were occluded in adult mongrel dogs to investigate pelvic hemodynamics. When the unilateral common iliac artery was occluded, the blood flow making a "stopover" within the pelvis was found to be significantly less than that of anatomical hemodynamics even under a resting condition. The blood flow decreased more significantly under exercise loading than under a resting condition, which demonstrates the presence of the "steal" phenomenon. This only occurs in the collateral circulation in the pelvis formed by two arterial systems which are related in a series. In deciding the appropriacy of reconstruction for the internal iliac artery in patients with aorto-iliac occlusive disease, this "steal" phenomenon should be kept in mind. In most cases, ischemic symptoms in pelvic organs may be due to a simple decrease of the blood flow supplied to the pelvis, or due to the "steal" phenomenon. If the pelvic region is in the state of ischemia owing to the "steal" phenomenon, reconstruction of the blood vessels flowing into the pelvis is not required. PMID- 8191915 TI - Quantitative evaluation of 99mTc-GSA in the rat liver after ischemia-reperfusion injury. AB - 99mTc-DTPA-galactosyl human serum albumin (Tc-GSA) is a new liver-imaging agent which binds specifically to hepatic binding protein. The purpose of this study was to evaluate the usefulness of Tc-GSA in quantitatively evaluating hepatic ischemia-reperfusion injury in the rat. Regional hepatic ischemia was induced by clamping the left hepatic artery and the left portal vein for 5 to 45 min. A hepatic accumulation index (t90) was obtained on the basis of the dynamic data. A significant difference of this index was observed between all ischemic groups and the control. In conclusion, 99mTc-GSA appears useful for evaluating the hepatic ischemia-reperfusion injury. PMID- 8191916 TI - Ovarian metastasis in patients with colorectal carcinoma. AB - The records of 159 patients who underwent surgical resection of colorectal cancer were reviewed to assess the incidence of ovarian metastasis and to define the role of oophorectomy. Four of these patients presented with metachronous metastases, and one patient had synchronous ovarian involvement. The incidence of ovarian involvement was higher in younger patients. While most patients with ovarian involvement had the primary tumor located at the rectosigmoid region, a similar distribution of the primary tumor was observed in patients without ovarian metastasis. The histological type and degree of differentiation was similar regardless of whether or not ovarian metastasis was present. Of the patient without ovarian metastasis, 57% presented with nodal metastases and 3.2% with peritoneal dissemination, while all patients with ovarian metastasis had nodal and peritoneal involvement. Our results suggest that histological type and degree of differentiation of the primary tumor do not influence likelihood of ovarian metastasis. However, the exposure of the tumor to the serosal surface and the subsequent peritoneal dissemination may be an important route by which malignant tumor cells reach the ovaries. However, due to the wide lymphatic involvement in patients with ovarian metastasis, the lymphatic route may be important as well. Thus, we consider that oophorectomy should be performed in all postmenopausal women, when the ovaries are macroscopically affected, and in premenopausal patients with Astler-Coller B2 tumors or over. PMID- 8191917 TI - Synergistic effect of tumor necrosis factor-alpha and interferon-alpha on the induction of apoptosis detected by BM-1/JIMRO: a new marker of apoptosis. AB - The effects of the combination of natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural human interferon-alpha (nHuIFN-alpha) on the induction of apoptosis were investigated by immunohistochemical analysis with BM-1/JIMRO monoclonal antibody in RPMI 4788 tumor cells. Few tumor cells in the control culture could spontaneously undergo apoptosis. The number of positive cells increased at 2 and 4 h after treatment with nHuTNF-alpha (1 x 10(5) U/ml) and nHulFN-alpha (1 x 10(5) IU/ml). This effect was clearly maintained from 8 h up to 72 h of culture. The number of apoptotic cells also greatly increased with doses, suggesting that the apoptosis induced by nHuTNF-alpha and nHuIFN-alpha in combination was dose-dependent. nHuTNF-alpha or nHuIFN-alpha alone could induce apoptosis, but the induction increased significantly when the two cytokines were combined. These findings indicate that by combining nHuTNF-alpha and nHuIFN-alpha apoptosis can be synergistically induced in RPMI 4788 tumor cells, and may have specific therapeutic implications for clinical treatments using these two cytokines. PMID- 8191918 TI - Computer generated three-dimensional reconstruction of the bony labyrinth in Mondini's dysplasia. AB - The bony labyrinth obtained at necropsy in four cases was studied by a new computer-generated three-dimensional (3-D) system. One case was normal (control) and the other three were histopathologically confirmed cases of Mondini's dysplasia. In case 1, the cochlea had only 2 turns and the lateral semicircular canal did not make a circle but appeared as a spherical mass projecting from the utricle even though the posterior semicircular canal made a normal circle. In case 2, there were no turns in the cochlea even though the semicircular canals and the vestibule appeared normal. In case 3, the cochlea showed 1 to 1 and 1/2 turns and the semicircular canals were premature showing only bud-like projections. This 3-D imaging system, which utilizes the toggling method, provides a way of obtaining satisfactory images without markers, and the time required to obtain these 3-D images was reduced by using a video camera instead of a digitizer. One of the problems associated with the use of 3-D imaging is the long processing time. We resolved this by inputting the section images with a video camera and by picking up structures using density segmentation instead of tracing with a digitizer. PMID- 8191919 TI - Unresponsiveness of antidonor cytotoxic T cells in a long-term stable renal transplant recipient. AB - The antidonor immune response was examined in a one haplotype-mismatched renal transplant recipient with an allograft that had been well-functioning for more than 10 years. Although the relative response of the mixed lymphocyte reaction (MLR) was (45.8)% and the MLR responder cells stimulated by donor cells produced measurable amounts of interleukin-2 (IL-2) (11.6 U/ml), the cytotoxic T lymphocytes (CTL) could not be generated against donor cells, even with exogenous IL-2. These results indicate that antidonor CTL precursors were either deleted or inactivated in this recipient. PMID- 8191920 TI - Clinicopathological analysis of de Quervain's disease. AB - Excised extensor retinacula of the first compartment and tenosynovium from 35 patients (6 men and 29 women) with de Quervain's disease were examined by light and electron microscopy to investigate the pathogenic mechanism. The patients, aged from 22-78 years, averaging 50 years, comprised the study group. Two hundred and thirty-two specimens from cadavers of 95 men and 75 women were macroscopically examined as the control. In the study group, the extensor retinaculum and tenosynovium were macroscopically thickened, and were histologically classified into 4 groups based on presence or absence of septum, and the location of retinacular thickening. Morphologically, the thickening of the tenosynovium and retinaculum was due to fibrosis in every layer, although fibroses were seen mainly in the middle layer. The ratios of proliferation of fibroblasts, myxoid changes and/or hyaline degeneration, and vascular proliferation were varied between layers. Minimal round cell infiltration was found in the retinaculum as well as in the tenosynovium. The results also indicate that the Iwahara-Nozue test can be used to accurately predict relatively greater thickening of the retinaculum on the extensor pollicis brevis side. Based on clinicopathological analyses, it appears that de Quervain's disease is induced not only by extrinsic factors such as superficial friction but also by intrinsic factors. PMID- 8191921 TI - Perspectives: a practical guide to the use of pamidronate in the treatment of Paget's disease. PMID- 8191922 TI - Evidence for both generalized and regional low bone mass among elderly women. AB - The consistency of bone mass measurements across bone sites was examined in a cohort of elderly Japanese-American women. The study included 744 women of mean age 66.6 years (age range 47-82 years) who had bone densitometry measurements at the spine, calcaneus, and distal and proximal radius. The women were classified at the four bone sites as in the lower, middle, or upper bone mass tertile for their age. Slightly more than half (56%) of the women were in the lower tertile at one or more of the bone sites, and such women were usually in the lower category at more than one site. Of the women, 24% were classified in the lower tertile at all four sites. Furthermore, as a group, women classified as in the low bone mass category at any one site had a low average bone mass at all four sites. Prospectively, the number of low bone mass sites predicted the risk of new spine fractures after adjusting for age and the number of spine and nonspine prevalent fractures. The risk increased approximately 1.3-fold for each additional low bone mass site. A subgroup (15%) of the population had marked heterogeneity in bone mass between sites. These women had one or more lower tertile bone mass site(s) and one or more upper tertile bone mass site(s). The results suggest that osteoporosis may occur as either a generalized or as a regional disorder. PMID- 8191923 TI - Influence of early age at menopause on vertebral bone mass. AB - Menopause leads to rapid bone loss, mainly as a result of estrogen deficiency superimposed on the age-related linear bone loss. The influence of age at menopause on bone loss is unclear, although early menopause is widely considered a risk factor for osteoporosis. Vertebral bone mineral density (BMD) was measured in 1667 women divided into five groups according to hormonal status and age at menopause. Menopausal status was an independent predictor of BMD in a multiregression analysis, along with current age, years since menopause (YSM), weight, and height. For the same chronologic age (55 years), women with early menopause had a 15% lower BMD and a higher YSM than women whose menopause occurred later ("normal" menopause). After adjusting for the interval since menopause, postmenopausal women with early menopause were found to have lower vertebral BMD than postmenopausal women with normal menopause. Finally, after the age of 60, 66% of the women with early menopause had a BMD that was below the fracture threshold compared to 18% of the women with normal menopause. The results of this cross-sectional study suggest that early menopause is associated with a quantitatively higher bone loss than in women with menopause of later onset and thus constitutes a risk factor for osteoporosis. PMID- 8191924 TI - Diagnostic value of estimated volumetric bone mineral density of the lumbar spine in osteoporosis. AB - Bone mineral density (BMD) measurements by dual-energy x-ray absorptiometry (DXA) are planar measurements. By measuring planar BMD in anteroposterior (AP) and lateral projections, it is possible to estimate the volumetric BMD by assuming that the vertebral body is an ellipsoid cylinder. Correction for the third dimension could improve the diagnostic accuracy of spinal BMD measurement in osteoporosis. The aims of this study were (1) to determine the effect of aging on volumetric BMD compared to planar measurements; and (2) to evaluate the diagnostic accuracy of volumetric BMD in comparison to planar measurements. We studied 26 postmenopausal women with osteoporotic vertebral fractures and 114 age and sex-matched controls without vertebral fractures from a population-based group. AP and lateral decubitus BMD of the lumbar spine were measured by DXA using a Lunar DPX (precision error for AP measurement, 0.8%; for lateral measurement of vertebra L3, 6.4%). Between the ages of 51 and 85 years the decreases in volumetric BMD of L3 (vol L3), lateral BMD of L3 (lat L3), AP BMD of L3 (AP L3), and AP BMD of L2-4 (AP L2-4) were 31, 28, 17, and 17%, respectively. The decrease in BMD compared to controls in the osteoporotics for vol L3, lat L3, AP L3, and AP L2-4 were 31, 34, 23, and 23%; expressed as Z scores, the decreases were -1.36, -1.33, -1.46, and -1.47 standard deviation units. The areas under ROC analysis curves for vol L3, lat L3, AP L3, and AP L2-4 were 85, 86, 87, and 87%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191925 TI - Bone marrow from mechanically unloaded rat bones expresses reduced osteogenic capacity in vitro. AB - Bone formation during mechanical unloading is reduced, mainly as a result of osteoblastic hypofunction. At the same time, the total number of osteoblasts per long bone is also markedly reduced. We tested the hypothesis that the number of osteogenic precursors present in the bone marrow stroma was concomitantly diminished by using an in vitro cell culture system in which femoral adherent bone marrow cells differentiate into active osteoblasts and produce bone-like nodules. Hindlimbs of 32-day-old male rats were either immobilized (unloaded) by sciatic neurectomy (immo) or sham operated (sham) and animals were killed after 11 days. Femora were either ashed to determine bone mass or used to generate bone marrow cultures. Adherent marrow cells were cultured in the presence of ascorbic acid, beta-glycerophosphate, and dexamethasone. Bone mass was significantly reduced in unloaded femora (by 16%) and tibiae (by 18%). The number of adherent cells (determined on day 6) was reduced by 50% in the immo group. Reduced cell number did not result from slower proliferation in culture since [3H]thymidine incorporation on days 4 and 6 was similar in the two groups. The osteogenic potential in vitro of marrow from unloaded bones was diminished compared with that from loaded ones as evidenced by (1) lower alkaline phosphatase (ALP) activity per mg protein (by 25-40%, examined on days 6 and 12), and (2) reduced nodule formation (by 70%, expressed as percentage of the dish area stained with Alizarin Red S on day 21). None of these changes occurred in the contralateral limb of operated (immobilized) animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191926 TI - Characterization, regulation, and function of specific cell membrane receptors for insulin-like growth factor I on bone endothelial cells. AB - It is now widely accepted that insulin-like growth factor-I (IGF-I) has a local regulatory role in bone remodeling. IGF-I has also been demonstrated to regulate proliferation of bone-derived endothelial cells. Such studies suggest a role of IGF-I in skeletal angiogenesis. Using BBE cells, a bovine bone endothelial cell line, we characterized the kinetics and chemical properties of IGF-I receptors and examined the effect of IGF-I on bone endothelium migration. Two classes of binding sites with high affinity for IGF-I were detected by binding experiments on bone endothelial cells. Both competition analyses and cross-linking studies revealed the presence of type I IGF receptor in bone endothelial cells. Moreover, these cells produced and released authentic IGF-I into the medium, as evidenced by radioimmunoassay analyses of gel-filtered conditioned media. Both IGF-I binding capacity and release decreased either with increases in cell number or after treatment with 17 beta-estradiol (17 beta E2) and parathyroid hormone (PTH). Both hormones also inhibited chemotactic responses of bone endothelial cells to IGF-I. Taken together, these results strongly suggest that IGF-I, a growth factor that promotes the proliferation of various bone cell types, also induces growth and chemotactic responses in bone endothelium acting through the type I IGF receptor. This may be part of a generalized response of bone cells to IGF-I that facilitates cell migration. PMID- 8191927 TI - Loss of parathyroid hormone-stimulated 1,25-dihydroxyvitamin D3 production in aging does not involve protein kinase A or C pathways. AB - Intestinal calcium absorption declines with aging as a result of decreased renal 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] biosynthesis. At least part of the decline in 1,25-(OH)2D3 may be due to acquired resistance to parathyroid hormone (PTH) stimulation of renal 25-hydroxyvitamin D1-hydroxylase (1-OHase) activity. To test whether aging rats can increase 1,25-(OH)2D3 production in response to PTH, male rats of the same litter were fed a normal Ca diet and were sacrificed at 175-225 g (young rats) or 3 months later at 350-425 g (aging rats). At sacrifice, basal serum 1,25-(OH)2D3 levels (88 +/- 16 versus 49 +/- 8 pg/ml, P < 0.05) and in vitro renal proximal tubule 1-OHase activity (178 +/- 15 versus 77 +/- 5 pmol/mg protein/5 minutes, n = 6, P < 0.001) were lower in aging animals. rPTH-(1-34) (10(-11) or 10(-7) M) increased in vitro 1,25-(OH)2D3 secretion by perifused renal proximal tubules from young but not aging rats. For young and aging rats, rPTH-(1-34) (10(-7) M) increased proximal tubule cAMP-dependent protein kinase (PKA) activity, and lower concentrations (10(-11) M) stimulated translocation of protein kinase C (PKC) activity from cytosolic to soluble membrane proximal tubule cell fractions. The results of this study show that PTH activation of 1,25-(OH)2D3 production may involve both signaling pathways, with the PKC pathway responsive to lower concentrations of the hormone. The acquired resistance to PTH stimulation of 1,25-(OH)2D3 production in aging appears not to involve the hormonal activation of PKA or PKC. PMID- 8191928 TI - Two-site enzyme immunoassay for measuring intact human osteocalcin in serum. AB - We developed a sensitive two-site sandwich ELISA for quantitative analysis of human osteocalcin in serum or plasma. Our method is based on two different highly specific antibodies recognizing epitopes at different ends of the protein so that only intact osteocalcin is detected. The method is fast (total analysis time less than 6 h/96 wells), precise (intraassay variation less than 2.3% at four different levels; n = 10, and interassay variation less than 2.5%, n = 5, respectively), and accurate, with a mean recovery of 105%. The detection limit in serum is approximately 0.1 micrograms/liter. The mean concentration of osteocalcin in normal serum with this assay is 3.3 micrograms/liter (SD 3.7 micrograms/liter; range 0.1-13.1 micrograms/liter; n = 41), and the reference range is 0.28-10.1 micrograms/liter (10 and 90% confidence limits). The method shows a reasonable positive linear correlation with other osteocalcin assays (Incstar, r = 0.55, p < 0.05, n = 13; Henning Oscatest, r = 0.52, p < 0.005, n = 34). A good correlation (r = 0.70, p < 0.001) between individual osteocalcin and bone-specific alkaline phosphatase serum concentrations was observed in normal subjects. We found a low or undetectable concentration of intact osteocalcin in serum of all four of our patients with acute primary hyperparathyroidism, and in all five patients with hypocalcemic secondary hyperparathyroidism, which suggests that PTH effectively inhibited the synthesis of osteocalcin in osteoblasts. The serum concentration of intact osteocalcin was elevated in two of three patients with chronic primary hyperparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191929 TI - Evidence for a diminished maturation of preosteoblasts into osteoblasts during aging in rats: an ultrastructural analysis. AB - Bone is subject to continuous remodeling throughout life. The age-related loss of (trabecular) bone, leading to senile osteopenia, is mainly due to impaired bone formation. Osteoblasts (OB) and osteoclasts (OC) have been identified as playing a crucial role in the process of bone turnover, but the contribution made by their precursors is not well documented. We analyzed the cells of the osteoblast and osteoclast cell lineage along the trabecular bone of tibiae and the stromal cells in the marrow of aging BN/Bi Rij rats using electron microscopy. It appeared possible to distinguish preosteoblasts (pre-OB), OB, preosteoclasts (pre OC), OC, and inactive bone-lining cells. Periods of increase, the maximal peak, and the decrease in trabecular bone volume were defined by means of morphometric measurements of trabecular bone volume. We found a decrease of more than 10-fold in the number of OB with age, but the numbers of pre-OB, pre-OC, and OC expressed per unit bone length, although variable, were age independent. The relative bone resorption and formation surface, expressed as a percentage of the total bone surface, decreased 2- and 15-fold, respectively. In 2-year-old animals the total volume of stromal cells, part of which constitutes the stem cell compartment of the osteogenic lineage, was a quarter of that found in 1-month-old animals and a third of that found in 6-month-old animals. The loss of trabecular bone is concomitant with a sharp increase in the ratio of pre-OB/OB, the ratio of OC/OB, and in the ratio of resorption to formation surfaces. There was no relation between the ratio of pre-OC/OC with age. These data lead to the conclusion that the main factor causing bone loss with age is a diminished maturation of pre-OB into OB. PMID- 8191930 TI - Deposition of cement at reversal lines in rat femoral bone. AB - Femora from young adult Wistar rats were prepared for both light and electron microscopy. Routinely processed wax sections showed the appearance of cement lines immediately proximal to the resorption surface formed by active osteoclasts and distal to the onset of lamella formation in femoral bone tissue. This early stage of extracellular matrix elaboration at reversal lines was then studied by scanning electron microscopy (SEM) of actively remodeling sites, mainly on trabecular and endosteal surfaces. The resorption surface was shown to comprise a decalcified collagenous mat with individual fibers running either parallel or perpendicular to the surface plane. By examining different, neighboring, areas of resorption lacunae, a temporal sequence of new extracellular matrix production could be established. Before the deposition of new collagen, globular accretions were deposited onto the resorption surface. In areas where individual collagen fibers were oriented perpendicular to the surface plane, this globular matrix was initially deposited on the exposed fiber tips. The globules increased in size and fused laterally to form a continuous cement layer, which not only interdigitated with the collagen mesh of the resorption surface but also provided anchorage for new collagen fibers, which themselves became mineralized. These morphologic results provide a mechanistic explanation of coupling at reversal lines. PMID- 8191931 TI - Effects of medium acidification by alteration of carbon dioxide or bicarbonate concentrations on the resorptive activity of rat osteoclasts. AB - Little is known about the extracellular conditions or factors that stimulate mature osteoclasts to resorb mineralized tissues. Isolated mammalian osteoclasts are strongly stimulated by protons in HEPES-buffered culture media in the absence of CO2 and HCO3-, but it has been reported that cell-mediated Ca2+ release from bone organ cultures is increased only when media are acidified by reduction of HCO3- concentrations, and not by increasing PCO2 (considered models of metabolic and respiratory acidosis, respectively). We investigated this question using disaggregated rat osteoclasts cultured on dentin slices for 24 h. The number of pits resorbed per osteoclast was stimulated in media acidified by manipulation of either HCO3- or CO2 concentrations. In experiments in which incubator CO2 was varied, resorption was almost abolished in the presence of 2.5% CO2 at pH 7.61 but increased in a stepwise manner up to 1.3 pits per osteoclast when dentin slices were cultured with 10% CO2 at pH 6.97. The depths and widths of pits, measured using a confocal laser reflection microscope, also tended to increase with increasing CO2 and decreasing pH. However, in experiments where pH was lowered by reducing medium HCO3-, pit size decreased, partially offsetting the increased number of pits resorbed per osteoclast. These findings suggest that rat osteoclasts may be more sensitive to stimulation by CO2 acidosis than by HCO3- acidosis, at least in the short term, and may possibly reflect local regulatory processes in bone. PMID- 8191932 TI - Effects of kistrin on bone resorption in vitro and serum calcium in vivo. AB - In many cell systems, cell-cell and cell-matrix interactions are mediated by integrins, a family of cell surface heterodimeric glycoprotein receptors. Osteoclast integrins may play a role in the process of bone resorption. Osteoclasts express the alpha v and beta 3 subunits of the vitronectin receptor and adhere to a wide range of proteins in vitro, all which contain the amino acid sequence Arg-Gly-Asp (RGD), an adhesion site recognition sequence common to many protein ligands that bind to integrins. The effect of kistrin, an RGD-containing snake venom protein, on osteoclast-mediated bone resorption was investigated in vivo and in vitro. When kistrin was infused into normocalcemic and hypercalcemic mice, serum calcium was significantly lowered at 3 and 6 h after the start of infusion, indicating an inhibitory effect on osteoclast activity in vivo. In vitro, kistrin potently inhibited bone resorption by isolated rat osteoclasts cultured on slices of bovine bone, and kistrin also inhibited the attachment of 293 cells expressing recombinant human alpha v beta 3 to fibrinogen (IC50 = 1 nM). These results indicate the potential therapeutic use of RGD-containing molecules for hypercalcemia of malignancy or for other disorders associated with bone loss. PMID- 8191933 TI - Expression of bone morphogenetic protein messenger RNA in prolonged cultures of fetal rat calvarial cells. AB - In addition to structural proteins of bone, such as type I collagen, bone cells synthesize a number of growth regulatory peptides that are also stored in the bone matrix, presumably as a consequence of local production by osteoblasts. Among the bone growth regulatory peptides found in the bone matrix are the recently described bone morphogenetic proteins (BMPs). These factors were purified from bone matrix by their capacity to stimulate ectopic bone formation, but it is not known whether they are produced by normal bone cells and influence normal bone formation. To determine whether they are expressed by normal osteoblasts during differentiation, we used the technique of prolonged primary culture of fetal rat calvarial osteoblasts. These cultures have been shown to be an informative model for studying expression of bone-related genes by cultured osteoblasts, since specific genes are expressed as the cells undergo proliferation and differentiation. We found that the bone morphogenetic proteins 1, 2, 4, and 6 are expressed by cultures of fetal rat calvarial osteoblasts before they form mineralized bone nodules and as they express alkaline phosphatase, osteocalcin, and osteopontin. This model can be used for study of regulation of expression of bone morphogenetic proteins by osteoblasts. PMID- 8191934 TI - Effect of ipriflavone on expression of markers characteristic of the osteoblast phenotype in rat bone marrow stromal cell culture. AB - The effects of ipriflavone on cellular proliferation and differentiation of osteoblasts were investigated using stromal cells isolated from the femoral bone marrow of young rats. To induce the formation of mineralized bone-like tissue in vitro, the cells were cultured in the presence of beta-glycerophosphate and dexamethasone. Ipriflavone was added when subculturing was started. After 14 days of culturing with ipriflavone (10(-7)-10(-5) M), increases in both the alkaline phosphatase activity and the hydroxyproline content per culture dish and a slight decrease in the saturated cell density were observed. Furthermore, continuous treatment with ipriflavone for 14-33 days resulted in an increase in the area of bone-like mineralized tissue accompanied by an increase in the secretion of osteocalcin. When culture medium lacking dexamethasone was used, rat bone marrow stromal cells neither differentiated into osteoblasts nor formed bone-like tissue, and under these conditions, ipriflavone had no effect on the proliferation or the phenotypic expression of the cells. These results suggest that ipriflavone directly stimulates markers of the osteoblast phenotype at a certain stage in bone formation without affecting undifferentiated cells that have not been committed to the osteogenic lineage. PMID- 8191936 TI - Long-term exercise of young and adult female rats: effect on femoral neck biomechanical competence and bone structure. AB - The present study was designed to examine the effect of exercise on femoral neck bone structure and strength in female rats after 4 and 10 months of exercise. Female Fischer rats aged 2 months were exercised for 4 h a day, 5 days a week on a motor-driven treadmill the speed of which was gradually increased until a daily distance of 2 km was reached. The training level was maintained for 4 months (n = 15) and 10 months (n = 15). Sedentary age-matched rats served as controls (n = 30). At death the proximal third of both femora was obtained from each rat. The left femoral neck was tested in a materials-testing machine, and the right was used for either trabecular bone mass measurement (BV/TV) or scanning electron microscopy (SEM). Biomechanical testing revealed a significant training-induced increase in femoral neck bone strength after 4 months of exercise, which although not accelerated was preserved after 10 months of exercise. Histologic investigation revealed a significant training-induced increase in BV/TV, accounted for by a significantly smaller proportion of marrow space. No difference in cortical area was found. Both histology and SEM revealed a tendency to an earlier closure of the growth line in the exercised animals. However, the exercised animals aged 6 months had a significantly increased total femoral length compared with the sedentary rats. No difference was found in total femoral length between sedentary and exercised rats aged 12 months. On the basis of this study, it is concluded that exercise has a positive effect on femoral neck bone strength.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191935 TI - Macrophage colony-stimulating factor restores bone resorption in op/op bone in vitro in conjunction with parathyroid hormone or 1,25-dihydroxyvitamin D3. AB - The in vivo administration of macrophage colony-stimulating factor (M-CSF) restores osteoclastogenesis and bone resorption in the op/op murine osteopetrosis. In vitro, exogenous M-CSF has been shown to be necessary for the generation of osteoclast-like cells in cocultures of hematopoietic and mesenchymal cells obtained from this mutant. In this study we investigated the capacity of M-CSF and other cytokines and hormones, alone or in combination, to induce bone resorption in explants of op/op metatarsals and metacarpals prelabeled with 45Ca. The effect on bone resorption was verified by counting the number of osteoclasts generated in the mineralized matrix. No osteoclast formation and no bone resorption were observed in the absence of M-CSF. M-CSF alone had only a slight effect at the high concentration of 10(4) units/ml. Addition of PTH or 1,25-(OH)2D3 together with M-CSF induced both osteoclastogenesis and bone resorption. The release of 45Ca was linear with time up to 15 days. PTH or 1,25-(OH)2D3 could not be substituted by TNF-alpha or IL-1, whereas IL-6 had a weak effect. M-CSF could not be replaced by GM-CSF. This study further emphasizes the role of M-CSF, PTH, and 1,25-(OH)2D3 in osteoclastogenesis. PMID- 8191937 TI - Osteoporosis in men with a history of tibial fracture. AB - The long-term effects of bone fractures on bone mineral density (BMD) at various skeletal sites are poorly established, although a serious fracture, such as a tibia fracture, followed by long immobility and disuse may lead to permanently decreased BMD and, through this mechanism, may be a risk factor for osteoporotic fractures in later life. To determine whether such an injury leads to osteoporosis, we measured the areal BMD (g/cm2) from the lumbar spine (L2-4), right distal radius and ulna, and the femoral neck, distal femur, patella, proximal tibia, distal tibia, and calcaneus of both extremities in 14 men with a history of primarily nonunited (finally bone-grafted) shaft fracture of the tibia and 20 men with a history of primary union. For evaluation of the patients' BMD in the spine and distal forearm, 22 age-, weight-, and height-matched normal men were also measured. The average time of immobilization in a long plaster cast was 27 weeks in the former group of patients and 16 weeks in the latter. The measurements were performed an average of 9 years after the fracture using a dual energy x-ray absorptiometric scanner. Compared with normal men (mean +/- SD = 1.116 +/- 0.160), the spinal BMDs were significantly lower in men with a history of a primary nonunion (0.979 +/- 0.100, -12.3%) and union (1.010 +/- 0.124, 9.5%). In distal radius and distal ulna, there were no significant differences between the three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8191938 TI - Effect of growth hormone, insulin-like growth factor I, basic fibroblast growth factor, and transforming growth factor beta on cell proliferation and proteoglycan synthesis by avian postembryonic growth plate chondrocytes. AB - We examined the in vitro effects of pituitary-derived chicken growth hormone (cGH), recombinant human insulin-like growth factor-I (rhIGF-I), recombinant human basic fibroblast growth factor (rhbFGF), and porcine transforming growth factor beta (pTGF-beta) on proliferation ([3H]thymidine uptake) and matrix proteoglycan synthesis (35SO4 incorporation) by chicken epiphyseal growth plate chondrocytes. Factorial experiments were used to study the effect of these substances in a serum-free culture system. Basic FGF had to be present in the culture medium for mitogenesis to take place. In the presence of this peptide, TGF-beta, TGF-beta + IGF-I, and newborn calf serum (NCS) stimulated mitogenesis. The mitogenic activity of NCS could be duplicated by adding platelet-derived growth factor (PDGF) to the culture medium. For matrix synthesis, IGF-I was the key factor, with the addition of TGF-beta, TGF-beta+bFGF, or serum producing further stimulation in matrix synthesis. Using this culturing system, homologous cGH did not stimulate cell proliferation or proteoglycan synthesis. The lack of stimulatory activity of cGH was consistent, regardless of the age of the birds from which the chondrocytes were isolated, the zone of the growth plate, or the level of cGH used. None of the growth factors used in this study or several other systemic hormones were found to be permissive factors for GH to be active. Either other factors must be present for a direct effect of GH on growth plate chondrocytes, or the avian species differ from their mammalian counterpart. PMID- 8191939 TI - [Flow index: a substitute for uroflow nomograms?]. AB - One hundred and twenty-nine flowmetries from an equal number of male patients with urinary obstructive symptoms have been analyzed, and the data provided by Siroky's nomogram compared to the flow ratios. Flow ratio was considered compatible with obstruction if below 0.80, which in turn correlated to -2 DE in Siroky's nomogram. Agreement between both parameters was noted in 95% cases (p < 0.05). The use of a flow ratio as a substitute for Siroky's nomogram to evaluate urinary obstructive disease would be justified by the easiness of interpretation, since it avoids translation of maximum flow and mean flow data to a plot. Flowmetry should only be considered determinant with clearly obstructive values. PMID- 8191940 TI - [Extracorporeal lithotripsy for urolithiasis: retrospective study of 227 patients]. AB - Presentation of a retrospective study in 227 lithiasic patients with indication for extracorporeal lithotrity (ESWL) as first line of therapy or as adjuvant treatment, referred to three lithotripter units over the last five years. There was a high percentage of personal history of lithiasis (55.5%), colic pain being the most frequent symptom (78%). Lithiasis largely affected one single renal unit, most often the left one (54.7%) and was solitary in 54.6% of cases. Calyceal and pyelic sites were the most common ones, the size of the stones ranging between 10-19 mm in 44.5% of cases. Overall results reflect a 78.5% success rate, with statistically significant lower occurrence of residual fragments in the right renal unit. There was greater success rates in ureteral calculi followed by calyceal ones and also in the smaller ones compared to those greater than 20 mm. Double-J ureteral catheterism was performed in 27% patients, with evidence of statistical significance between them and those uninstrumented in relation to occurrence of lithiasic trail. An 11% rate of significant complications requiring endourological handling due to obstruction in 7.5%, and open surgery in 3.5% due to complication or lack of resolution was detected. PMID- 8191941 TI - [Incidence of upper urothelial tumor in the Autonomous Community of La Rioja in 1976-1991]. AB - Study of the incidence rate of upper urothelium tumours between 1976 and 1991 among the population of the autonomous community La Rioja. A study by age, sex and time intervals, totalling 32 cases, is conducted. A greater incidence in males, and between 1987-1991 in terms of time, is observed. With regard to location of the upper urothelium tumour, a significant difference is found between right and left ureters and right and left renal pelvis. In 14 cases, an associated vesical carcinoma was noted (RR = 5338.9 with 95% CI from 2668.5 to 10681.4). PMID- 8191942 TI - [Determination of serum SCC antigen in transitional cell carcinoma of the bladder]. AB - The SCC antigen expresses in the squamous epithelium during the process of a neoplastic transformation. This paper's objective is to evaluate the biological behaviour of SCC antigen in surface, deep, localized and spread malignant vesical carcinoma. To this end, 100 patients divided in two groups were studied. The first group consisted in 30 healthy subjects strictly selected and the second group comprised 70 patients diagnosed with transitional cell vesical carcinoma. SCC Antigen measurement was made by Radioimmunoassay (RIA, Abbott). Our results suggest that this tumoral antigen has no use as a prognostic factor in patients diagnosed with transitional cells vesical carcinoma, since serum concentrations suffer no change in relation to size, extent and degree of tumoral differentiation. PMID- 8191943 TI - [Potentiation of cytotoxicity of electromagnetic shock waves by suramin, "in vitro" study]. AB - The objective of this experimental study is to assess the inhibition of tumoral cells growth induced by electromagnetic shockwaves at different energy levels in PC-3, the human prostate adenocarcinoma cell line. Also, an assessment is made of the inhibition of cell growth caused by adding Suramin to the growth medium and the enhancement of cytotoxicity when associated to that produced by electromagnetic shockwaves. Cells viability is determined by life staining exclusion methods and nucleoside incorporation. Cytotoxic action of electromagnetical shockwaves in the PC-3 cell line is dose dependent (p < 0001). Suramin significantly inhibits cell viability (p < 0001). The association of both therapeutical approaches enhances significantly their individual cytotoxicities (p < 0001). PMID- 8191944 TI - [Extracorporeal shock-wave lithotripsy in polycystic kidneys]. AB - Presentation of 6 cases (8 renal units) of lithiasis in polycystic kidneys treated with extracorporeal shockwave lithotrity (ESWL). One patient required puncture of a compressing cyst, prior to ESWL, to facilitate the stones removal. No complications were seen in any of the cases. Therefore, stones in polycystic kidneys can be safely and effectively treated by ESWL. PMID- 8191945 TI - [2,8 dihydroxyadenine(2,8 DHA) lithiasis. Report of 3 cases]. AB - Presentation of three cases of 2,8 dihydroxyadenine calculi. This is an infrequent but potentially serious form of lithiasis, of purinic origin, caused by a genetic abnormality (deficit of adenine phosphoribosyltransferase, APRT) affecting both sexes. Frequent confusion of this form with uric lithiasis forces to try the use of IR spectrum or X-ray diffraction. Long-term follow-up of these patients and treatment with allopurinol, avoiding alkalinizating agents, is essential. PMID- 8191946 TI - [Adrenocortical carcinoma with inferior vena cava thrombosis]. AB - Presentation of one case of a large non-functional left corticosuprarenal carcinoma with associated thrombosis of the left renal vein and abdominal cava vein, a location rarely reported in the literature. Correct pre-operative magnitude diagnosis was possible, thus allowing the use of the appropriate surgical technique leaving no need for improvisation. In spite of the overall poor prognosis of this malignant tumoration, even more when there is a venous extension, the patient is now free of relapse or tumoral metastasis three years after surgery. PMID- 8191947 TI - [Renal angioscopy]. AB - Presentation as a novelty of the application of endoscopic methods in the display of the renal artery (angioscopy). Review of findings seen in the renal artery of a donor corpse with polytraumatism using direct view with a MiniScope-type rigid urethroscopy and the possible future application of this technique. PMID- 8191948 TI - [Hydatid cyst and renal adenocarcinoma: an exceptional association]. AB - Presentation of one case of an exceptional association in the same renal unit of a hydatid cyst and an adenocarcinoma, in a female patient who arrived to the emergency service with a picture of haematuria and lower back pain. The paper discusses the diagnostic complications posed by the large central necrotic component of the tumour, the adjacent position of both lesions and, basically, the initial intention of performing conservative surgery after it was demonstrated that the patient had mild renal insufficiency and simple cysts in the other kidney. In the end, faced with the perioperative finding of a neoplastic-like mass, radical surgery was performed. Analysis of the diagnostic and therapeutical difficulties with complex cystic masses in general. PMID- 8191949 TI - [Renal adenocarcinoma with multicystic pattern]. AB - One growth pattern of renal carcinomas is the multicystic of multilocular cysts one, of which few cases have been published but which according to Hartman represent 15% of total cases. This variant of the renal tumour arouses great diagnostic and therapeutical uncertainties with multicystic kidney, biopsy after surgery being the test which provides true diagnosis. Presentation of two clinical cases and review of this condition. PMID- 8191950 TI - [Several comments and various considerations on Von Brunn nests]. AB - Subsequent to a certain amount of aggression, the vesical epithelium can induce some histological changes which would range from the most innocent morphological vicarious forms to the most aggressive neoplastic types (transitional, squamous and/or glandular tumours). Co-existence in the same urothelium of metaplastic, dysplastic and/or neoplastic lesions should not therefore be a surprise. With the intention of assessing the urothelium evolutive potential, we present a morphological study of the male cervix-trigonal epithelium abnormally involved in the steroidal hormones immunosuppression and actions. The typical patches of "female cervical trigonitis" have not been seen in this epithelium although there has been a wide range of evolutive possibilities of squamous and/or glandular lineage. Both tissular options have a clear metaplastic etiology. They present neither atypia not dysplasia, but participate of the distinctive dynamics of Von Brunn nidi. (C. Pellice Jr: Doctorate Thesis, 1990). Of all the various evolutive options displayed by the urothelium when subjected to aggression, this study will focus on the Von Brunn nidi because of their atypical behaviour, their peculiar histogenesis and their dubious and controversial participation in vesical carcinogenesis. PMID- 8191951 TI - [Reliability of CAT in the local staging of tumors of the upper urothelium]. AB - Presentation of a retrospective study where the reliability of computerized axial tomography (CAT) used in preoperative local diagnostic definition of 20 upper urothelium tumours (UUT) radically treated between 1985 and 1991 is analyzed. Of them, only 70% were located by CAT and, of these, only 56% (45% of total) obtained a clear correlation with their local infiltration stage. Thus, it is concluded that CAT alone is not a good method for the preoperative evaluation of UUTs, at least when it comes to indicate their likely conservative treatment. PMID- 8191952 TI - New, emerging, and reemerging infectious diseases. PMID- 8191953 TI - Geographic-specific genotypes or topotypes of human T-cell lymphotropic virus type I as markers for early and recent migrations of human populations. PMID- 8191954 TI - Recent developments in hepatitis delta virus research. PMID- 8191955 TI - Toroviruses of animals and humans: a review. PMID- 8191956 TI - Molecular studies of genetic RNA-RNA recombination in brome mosaic virus. PMID- 8191957 TI - New developments in fungal virology. PMID- 8191959 TI - British Geriatrics Society autumn meeting. London, 14-15 October 1993. Abstract. PMID- 8191958 TI - Regulation of human immunodeficiency virus infection: implications for pathogenesis. PMID- 8191960 TI - [Idiopathic maxillary bone cavity]. AB - Since buccal surgeons are sometimes unable to cure the so-called traumatic bone cysts, we reviewed the literature to find the most recent assumptions of its pathogenesis and the latest treatments proposed. PMID- 8191961 TI - [The role of implants in functional mandibular reconstruction]. AB - More frequently after oncological resection, the mandibular reconstruction is done with microsurgically anastomosed free flaps. The titanium implants propose to the patients an oral rehabilitation with best functional and aesthetic results. It is very true in oncological surgery with or without radiotherapy. PMID- 8191962 TI - [Primary correction of lip and nose abnormalities in complete unilateral cleft. 1: Lip reconstruction]. AB - This first part of an article on primary repair of the unilateral cleft lip and nose is dealing with the lip deformity. A differentiated labial and nasal muscle reconstruction is as important as an esthetic skin closure. A symmetrical bone platform and a limited tissue defect are ideal conditions for the definitive lip repair. The combination of a lip/nose adhesion and a growth guidance plate is able to create these conditions in a period of four months. PMID- 8191963 TI - [Mandibular fractures following insertion of dental implants]. AB - This article reviews the complications reported in the literature following treatment with dental implants. Special attention is given to mandibular fractures, the conditions leading to the fractures and their management. The authors report on 2 new patients who sustained mandibular fractures and 1 patient who nearly developed a fracture after receiving mandibular endosseous implants. PMID- 8191964 TI - Cystic compound odontoma in an unusual pericoronal posterior location. AB - The authors present a case of a compound odontoma located in a pericoronal location in the third molar region. The odontoma was in a radiolucent area enclosing the crown of the unerupted third molar. PMID- 8191965 TI - [Clinical application of a third generation lithotripter (Modulith SL20) for urinary tract calculi]. AB - A third generation lithotripter (Modulith SL20) was used for disintegration of upper urinary tract calculi. From April 1991 through March 1993, a total of 281 sessions were carried out on 212 patients with upper urinary tract calculi at Seichoukai Fuchu Hospital. One month after the last session, of the 141 patients evaluated, 55 (39.0%) were free from stone fragments and 52 (36.9%) had stone fragments equal to or smaller than 4 mm. The over-all successful rate was 75.9% and the success rate was excellent for lower ureteral stones. As side effects, there were no serious complications other than perinephritic hematoma which occurred in 2 patients. These findings clearly indicated that the Modulith SL20 lithotripter was highly useful for disintegration of calculi of the upper urinary tract. PMID- 8191966 TI - [In situ extracorporeal shock wave lithotripsy for ureteral stones causing acute renal failure]. AB - We discuss the effectiveness of in situ extracorporeal shock wave lithotripsy (ESWL) for the ureteral stones causing acute renal failure in 5 patients (4 men and 1 woman, mean age 56.2 years). Three of them had a sole functioning kidney, one had a solitary kidney and the other had bilateral ureteral stones. The obstructing stones were located in the upper ureter in one, lower ureter in 2, upper and lower ureter in one and bilateral upper ureter in one with the average length of the stones being 9.2 mm. We used the EDAP LT-01 device for these stones. The obstructing stones were successfully disintegrated by ESWL alone in three cases, but could not be disintegrated in the other 2 cases in which the obstruction had occurred gradually or there were multiple stones. In the latter 2 cases, we performed ESWL again with percutaneous nephrostomy or hemodialysis. We thus believe that ESWL is a safe and effective procedure and is the first choice of emergency treatment for some ureteral stones causing acute renal failure. However, the subject is limited to acute cases, and the stone must be easily detected, single with its size being less than 12 mm and composed of calcium. PMID- 8191967 TI - [Experimental studies on evaluation of the effects of radiotherapy and chemotherapy in urogenital tumors using 31P-magnetic resonance spectroscopy]. AB - The effects of local irradiation and intraperitoneal injection of cisplatinum (CDDP) and VP-16 were examined in the sequential 31P magnetic resonance spectroscopy (MRS) in testicular cancer (TC-1) and bladder tumor (BT-8) of human origin, serially transplanted in nude mice. In the early phase of tumor growth, high-energy phosphate metabolites such as phosphocreatinine (PCr), adenosine triphosphate (ATP) and phosphomonoester (PME) were detected in both grafted tumors. However, the relative value of inorganic phosphate (Pi) to PCr increased with the growth of the tumor. Irradiation had the most pronounced effect to inhibit growth, followed by CDDP in both strains. However, growth inhibition was not observed in the VP-16 group. The effect of irradiation on the tumor histology was severely expressed in the nucleus and cytoplasm on the 4th to 7th day. The high PCr/Pi ratio during 2 to 14 days after irradiation suggested reoxygenation in the tumors with a high hypoxic cell fraction. In the CDDP and VP-16 groups, without histological change, the changes of PCr and Pi were milder than that in the irradiation group. Thus the spectroscopic analysis is presumably expected to give us an earlier and more accurate information on the tumor than the conventional parameters. PMID- 8191968 TI - [Clinical evaluation of M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy for advanced urothelial cancer]. AB - M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy was performed on 27 patients with advanced urothelial cancer. The patients included 20 with bladder cancer, 4 with upper urinary tract cancer and 3 with both lesions. Complete response (CR) was observed in 2 (7.4 +/- 9.9%) patients and partial response (PR) in 10 (37.0 +/- 18.2%) patients after the treatment, i.e., the overall objective response rate was 44.4 +/- 18.7%. The rate of relapse or recurrence in the patients with CR and PR was 100% and 90.0%, respectively. The mean duration of the response was 18.5 +/- 13.4 months and 10.7 +/- 10.9 months for CR and PR, respectively. The overall survival rate after one year was 30.2%. Bone marrow suppression was the most serious side effect. The white blood cell count became below 1,000/microliters in 10 patients (36.7%). Among them, 4 patients suffered from sepsis. In conclusion, M-VAC chemotherapy was effective for induction therapy against advanced urothelial cancer, although the effective duration was short. Further maintenance therapy should be established. PMID- 8191969 TI - [Clinical investigation of clean intermittent catheterization]. AB - We evaluated 120 patients with neurogenic bladder treated by clean intermittent self catheterization (CIC) in our department. These cases were divided into 2 groups: early treatment cases in which CIC started within 1 year after onset of dysuria, and late treatment cases in which CIC started after more than 1 year. Urinary tract infections (UTI) were recognized in 35% of the early treatment cases and 80% of the late treatment cases in the subsequent period. Pyelonephritis was experienced in 4% of the early treatment cases and 12% of the late treatment cases. Antibiotics therapy was considered unnecessary for asymptomatic UTIs. After CIC treatment, hydronephrosis detected by intravenous pyelography (IVP) and ultrasonography was improved in 18 of the 20 cases, and no cases showed deteriorated renal function. In the cases with neurogenic bladder after radical operations of the uterus or rectum, 45% of the early treatment cases have become free from CIC within 3 months postoperatively, and 84% eventually became free. Most of the late treatment cases have been continuing CIC. We considered that CIC was unnecessary when the residual urine was less than 100ml based on the periodical urinalysis and observation of renal function. PMID- 8191970 TI - [A clinical study of the changes of bone lesions after parathyroidectomy in patients with secondary hyperparathyroidism]. AB - We evaluated the changes of the bone lesions and their relative bone findings before and after parathyroidectomy in 23 patients with secondary hyperparathyroidism. Before the operation, all patients had bone and/or joint pain. In radiographic findings, subperiosteal bone resorption of the hand and a salt and pepper coloration of the skull were observed in all patients. Rugger jersey spine and the disappearance of the lamina dura were observed in about 90% of the patients. The bone mineral contents measured by single photon absorptiometry and digital image processing method had decreased in all of the patients compared with the mean values in sex- and age-matched controls. After the operation, the bone and/or joint pain had disappeared excluding three patients with recurrent hyperparathyroidism. The bone changes of the hand and the skull had improved in about 90% of the patients. However, the improvement rate was low in the vertebral and dental bone changes. The bone mineral contents increased significantly compared with the preoperative values. In recurrent cases, transient increase of the bone mineral contents was observed postoperatively. However, their values, were decreased gradually with the elevation of parathyroid hormone level. The evaluation of the bone lesions before and after parathyroidectomy not only indicates the effectiveness of the operation but also illustrates the function of the autotransplanted parathyroid tissues. We conclude that regular examination of the bone lesions after parathyroidectomy, paying attention to recurrent hyperparathyroidism and/or graft function, is mandatory. PMID- 8191971 TI - [A case of renal liposarcoma]. AB - A-48-year-old male was admitted to our hospital with a right renal tumor. He received radical nephrectomy immediately. Histological examination of surgical specimen revealed renal liposarcoma, which consisted of mixed type of pleomorphic and well differentiated subtypes. Multiple tumorous lesions were scattered in the renal parenchyma. He has been alive without disease for 2 years and 7 months after surgery. Only 23 cases of renal liposarcoma have been reported in Japan. PMID- 8191972 TI - A case of papillary renal cell carcinoma suggestive of Bellini duct origin. AB - A case of Bellini duct carcinoma is reported. A left renal tumor was detected by abdominal computerized tomography in a 76-year-old male, although he had no symptoms, such as hematuria, weight loss or flank pain. Radical nephrectomy was performed under the diagnosis of renal cell carcinoma in the left kidney. Macroscopic examination of the resected kidney revealed a tumor 2.0 cm in diameter, with a yellow-brown cut surface, located in the renal medulla. Histological examinations showed malignant tumor cells with eosinophilic cytoplasm with a papillary growth pattern. Immunohistostaining examinations using Lectin and two kinds of monoclonal antibodies demonstrated no significant staining with soybean agglutinin, peanut agglutinin, Dolichos biflorus agglutinin, Lotus tetragonolobus agglutinin or cytokeratin, and negative staining with Tamm-Horsfall protein. Although the results of immunohistostaining did not provide support, both macroscopic and microscopic findings strongly suggested that this tumor originated from Bellini duct epithelium (Bellini duct carcinoma). The patient is alive with no evidence of disease 1 year after surgery. Bellini duct carcinoma is a rare malignant condition and the prognosis is usually poor. Differential diagnosis from other renal or pelvic tumors is difficult and long term careful follow-up is necessary. PMID- 8191973 TI - [Duplication of the inferior vena cava with left renal cell carcinoma]. AB - A case of duplication of the inferior vena cava (IVC) with left renal cell carcinoma is presented, and the clinical and radiological significance is discussed. Although computed tomographic (CT) scanning, inferior venacavography and renal venography revealed a sufficient amount of anatomical information, an accidental rupture to the inferior vena cava occurred during the procedure. The patient subsequently required 7 units of blood, and suffered acute hepatitis two months following the blood transfusion. However, no recurrences of renal cell carcinoma and hepatitis have been observed four year after the procedure. PMID- 8191974 TI - [Renal actinomycosis: a case report]. AB - A 56-year-old male presented with a history of dull pain in the abdomen, accompanied by anorexia and weight loss. On examination, he had a moderate tenderness in the right kidney region. Radiological investigation could not deny renal tumor, and the right kidney was removed. Microscopically, characteristic colonies of actinomyces were seen. Preoperatively it is difficult to differentiate renal actinomycosis and renal tumor. Removal of the involved kidney followed by appropriate antibiotic therapy may be promptly curative. PMID- 8191975 TI - [Ureteral polyp prolapsing from the external urethral meatus: report of a case]. AB - We herein report a case of a ureteral polyp treated with transurethral resection (TUR) in a 41-year-old female with the chief complaint of urethral tumor. Cystoscopic findings revealed the tumor originating from the right ureteral orifice. However, intravenous pyelography showed no abnormalities. We resected the tumor transurethrally and the histological diagnosis was ureteral polyp. The postoperative course was uneventful without any signs of vesico-ureteral reflux or recurrence of the polyp. This is the first case of ureteral polyp prolapsing from the external urethral meatus in the Japanese literature. PMID- 8191976 TI - [A case of uterine prolapse with hydroureter]. AB - We report a case of complete uterine prolapse with bilateral hydroureter. The patient was a 81-year-old woman with complete uterine prolapse suffering from dysuria and urinary incontinence. Bilateral moderate hydroureter happened to be revealed by drip infusion pyelography (DIP) but blood creatinine was normal. Hydroureter was ameliorated by vaginal hysterectomy. A brief discussion and review of the literature are given. PMID- 8191977 TI - [Genitourinary endometriosis: report of 2 cases and clinical aspects of patients in Japan]. AB - One hundred and fifty two cases of genito-urinary tract endometriosis reported in Japan including our 2 cases were reviewed. The incidence and mean patients' age were respectively 0.7% and 22 years old for kidneys, 37.5% and 38.8 years old for ureter and 61.8% and 36.2 years old for bladder. Clinical symptoms in ureteral endometriosis were similar to those in upper urinary tract obstruction and in vesical endometriosis, lower urinary tract symptoms such as pain on urination, irritative bladder symptoms and macrohematuria were frequently observed. Vesical lesions tend to be located on the posterior wall in the retrotrigone or trigone, and ureteral lesions tend to be located in the bilateral lower segments. The incidence of extrinsic type of ureteral endometriosis was 6 times higher than that reported as intrinsic type, and mixed type was reported in only 3.5%. Recent first choice for mild endometriosis is hormonal therapy with Danazole or LH-RH analogue. Surgical treatment is recommended in severe cases or patients in whom hormonal therapy is not effective. PMID- 8191978 TI - [Morphological changes of Kock pouch investigated by autopsy two years nine months postoperatively]. AB - A 62-year-old male patient consulted us because of gross hematuria and was diagnosed as having a bladder tumor. Total cystectomy was performed and a Koch pouch was utilized. Two years and nine months later, he died as a result of recurrence of bladder tumor and pathological autopsy was performed. A microscopic section of the reservoir mucosa showed a reduction in the number of crypts and an increase in the number of goblet cells. These morphological changes seemed to be caused by chronic exposure to urine, but have a favorable effect upon metabolic alterations following the utilization of the Kock pouch. PMID- 8191979 TI - [A case of capillary hemangioma of the testis in a child]. AB - Testicular tumors derived from connective tissue, blood vessels and musculature are uncommon and intratesticular tumors of vascular origin are extremely rare. A rare case of capillary hemangioma of the testis in a child is reported. An 11 year-old boy was admitted with the chief complaint of painless mass in the right scrotum. He was diagnosed with a right testicular tumor by physical examination and ultrasonography, preoperatively. Right high orchiectomy was done on December 10, 1990. The testis measured 2.5 x 2.3 x 1.5 cm. Pathologically, the tumor was diagnosed as a capillary hemangioma of the testis. PMID- 8191980 TI - The brain in older persons with and without dementia: findings on MR, PET, and SPECT images. AB - Neuroimaging plays an increasingly important role in the evaluation of dementias of older adults. Although no unequivocal diagnostic test other than biopsy is currently available for Alzheimer's disease and some other dementias during life, neuroimaging techniques are an integral part of the examination and follow-up of patients with dementia. This review describes findings in the brains of patients with normal aging and in elderly patients with dementia, as shown by MR imaging and MR spectroscopy, positron emission tomography (PET), and single-photon emission computed tomography (SPECT) and correlated with clinical and pathologic features. PMID- 8191981 TI - Positron emission tomography: a financial and operational analysis. AB - Positron emission tomography (PET) is an emerging clinical imaging technique that is facing the challenges of expansion in a period of imminent health care contraction and reform. Although PET began showing utility in clinical medicine in the mid-1980s [1], its proliferation into mainstream medical practice has not matched that of other new imaging technologies such as MR imaging. Many factors have contributed to this, including the changing health care economy, the high cost of PET, the length of time it takes to develop a PET facility, and its inherent complexity. In part because of the proliferation of the use of other technologies and the general explosion of costs, insurance carriers are now holding diagnostic techniques, including PET, to stricter standards of efficacy. New techniques must show improvement in long-term outcome of patients, a difficult task for diagnostic tools. In addition to these issues, PET is an expensive technology that requires highly trained multidisciplinary personnel. Questions have also been raised about the most appropriate mechanism for regulation of PET isotope preparation, leading to speculation about future regulatory requirements. The current pioneers of PET must meet these challenges in order for it to become a routine imaging technique. Because of its clinical value, PET will probably survive despite the challenges. For many reasons, though, not every hospital should necessarily develop PET services. Conversely, many hospitals without this technology should consider acquiring PET. The purpose of this article is to identify the financial, operational, and clinical challenges facing PET centers today, describe potential organizational configurations that may enable PET to survive in an antitechnology environment, and delineate which institutions should consider this new technology. PMID- 8191982 TI - Accessory fissures of the upper lobe of the left lung: CT and plain film appearance. AB - OBJECTIVE: The purpose of this study was to assess CT and chest radiographic features of accessory fissures of the upper lobe of the left lung. MATERIALS AND METHODS: Eighteen accessory fissures of the upper lobe of the left lung were identified on CT scans of 17 adult patients. The collimation was 10 mm in 12 patients and 8 mm in five patients. Additional, thinner sections (1.5-5.0 mm) were available for 12 patients. The segments separated by each fissure were identified by means of the individual segmental bronchi and vessels. Available chest radiographs were correlated with CT studies in 12 patients. RESULTS: The fissures separated the anterior segment of the left upper lobe from the superior segment of the lingula (left minor fissure) in 13 cases (72%), the superior from the inferior segment of the lingula in three cases (17%), and the apico-posterior from the anterior segment in two cases (11%). Ten (56%) of the 18 fissures could be seen only on thin sections. Eleven (61%) of the accessory fissures were incomplete. The fissures were classified into four types: convex laterally (n = 8), convex medially (n = 2), anteromedial (n = 5), and transverse (n = 3). On posteroanterior chest radiographs, the accessory fissure was evident in 10 (83%) of 12 patients. CT studies showed that nine of the 10 fissures seen on radiographs represented a left minor fissure, and the remaining fissure separated the two segments of the lingula. CONCLUSION: Accessory fissures of the upper lobe of the left lung, as shown by CT, can separate any two contiguous segments, are frequently incomplete, and occur in four different configurations. The left minor fissure is the most common of these fissures and the most frequently seen on chest radiographs. The ability to recognize accessory fissures of the left upper lobe should help in the segmental and topographic localization of pulmonary lesions. PMID- 8191983 TI - Bronchioloalveolar carcinoma. PMID- 8191984 TI - Congenital bronchopulmonary diseases in adults: CT findings. AB - Congenital lung disease is divided into two types: lesions that arise from the primitive foregut (i.e., bronchopulmonary malformations) and lesions that originate in the pulmonary vasculature. The latter often are detected early in life because of signs and symptoms or other serious associated anomalies. Conversely, many of the bronchopulmonary anomalies are asymptomatic and therefore are not discerned until adulthood. This essay illustrates the spectrum of CT findings of many congenital bronchopulmonary malformations that are seen in adults, including pulmonary agenesis, anomalous bronchial branching, bronchial atresia, foregut cysts, bronchopulmonary sequestration, and pulmonary arteriovenous malformations. PMID- 8191985 TI - Radiation pneumonitis caused by yttrium-90 microspheres: radiologic findings. PMID- 8191986 TI - Disseminated pulmonary ossification in end-stage pulmonary fibrosis: CT demonstration. PMID- 8191987 TI - Acute traumatic hemopericardium. PMID- 8191988 TI - Ductal carcinoma in situ of the breast: correlation between mammographic and pathologic findings. AB - OBJECTIVE: Ductal carcinoma in situ shows heterogeneous clinical behavior and response to treatment depending on its pathologic features. The aim of this study was to correlate the radiologic and pathologic features of ductal carcinoma in situ of the breast. Differences, if present, may allow refinement of diagnosis and selection of treatment options. MATERIALS AND METHODS: The mammograms of 128 patients with ductal carcinoma in situ of the breast were analyzed by a radiologist who knew that the patients had ductal carcinoma in situ but had no other pathologic information. The radiologic and pathologic features of subgroups characterized according to cell size and presence of necrosis were then compared. Statistical comparisons were made by using the chi 2- and Fisher's exact tests. RESULTS: Patients with small-cell ductal carcinoma in situ more commonly have a normal mammogram (28% vs 6%, respectively, p < .001) or an abnormal mammogram without calcification (42% vs 5%, respectively, p < .001) than do patients with large-cell ductal carcinoma in situ. Among patients with abnormal mammographic findings, calcification is present in 58% of those with small-cell ductal carcinoma in situ, compared with 95% of those with large-cell ductal carcinoma in situ (p < .001). No significant differences were found in the calcification morphology of small- and large-cell ductal carcinoma in situ. These features were seen more commonly in ductal carcinoma in situ with necrosis than in ductal carcinoma in situ without necrosis, respectively: abnormal mammographic findings (95% vs 73%, p < .001), calcification (96% vs 61%, p < .001), calcification with a ductal distribution (80% vs 45%, p < .005), and rod-shaped calcification (83% vs 45%, p < .001). An abnormal mammogram without calcification (39% vs 4%, p < .001) or predominantly punctate calcification (36% vs 13%, p < .05) was seen more commonly in ductal carcinoma in situ without necrosis than in ductal carcinoma in situ with necrosis, respectively. CONCLUSION: We have shown that the radiologic features of ductal carcinoma in situ vary according to cell size and the presence of necrosis in particular. Necrosis has been found to be a feature of more biologically aggressive in situ breast cancer, so these findings may be of practical value in deciding the management of indeterminate calcification clusters and whether to offer breast conservation. PMID- 8191989 TI - Mammograms obtained with rhodium vs molybdenum anodes: contrast and dose differences. AB - OBJECTIVE: A mammography unit with both a molybdenum anode and a rhodium anode, filtered with molybdenum and rhodium, respectively, was evaluated to determine which types of women would benefit from the dose savings of the rhodium combination despite some loss of contrast. SUBJECTS AND MATERIALS: In 100 women, the molybdenum anode and molybdenum filtration (Mo/Mo) were used to obtain mammograms of the right breast, and the rhodium anode and rhodium filtration (Rh/Rh) were used for mammograms of the left breast. All mammograms were obtained at 26 kVp. All milliampere-second values used to radiograph the breasts of these women were recorded. Mammograms of 54 women (30 with previous mammograms available), representing the four types of breasts as defined by the American College of Radiology, were interpreted by three radiologists. Each mammogram was assigned a grade for breast type, preference (Rh/Rh, Mo/Mo, or previous mammograms), contrast, and sharpness. RESULTS: Overall, mammograms obtained by using the Mo/Mo combination were preferred. However, for images of types 3 and 4 breasts, Rh/Rh was preferred twice as often as it had been for mammograms of types 1 and 2 breasts. The mean glandular dose for all breast types when the Rh/Rh combination was used was 42% of the dose used for the Mo/Mo combination. For a 6-cm-thick dense breast, the Rh/Rh combination required 40% of the dose required for the Mo/Mo combination. CONCLUSION: Mammograms obtained with the Rh/Rh combination carried an overall decrease in contrast and mean glandular dose. However, for young women and some women with large dense breasts, the Rh/Rh mammograms were equivalent to or better than the mammograms obtained with the Mo/Mo combination. Effective use of Rh/Rh units requires careful selection of women based on age or the amount of glandular tissue seen on previous mammograms. PMID- 8191990 TI - Invasive lobular carcinoma in a patient with synchronous ductal carcinoma in situ: detection with MR imaging. PMID- 8191991 TI - Cavernous hemangioma of the pectoralis muscle mimicking a breast tumor. PMID- 8191992 TI - The use of antispasmodic drugs during barium enemas. AB - In 1958, Welin recommended the routine use of atropine before a barium enema to reduce mucus secretion and make the examination more comfortable. Currently, many radiologists believe that smooth-muscle spasmolysis is a useful adjunct during a barium enema and use such a spasmolytic agent. One survey found that spasmolytic agents were administered more frequently in 1987 than in 1976. The use of glucagon had increased 20% between 1976 and 1987. Among 34 foreign institutions responding to the survey, 37% used glucagon and 45% used scopolamine butylbromide (Buscopan). Nevertheless, it is still controversial whether spasmolytic agents play a significant role in the performance and interpretation of a barium enema. Some radiologists routinely use a spasmolytic agent; others do so only selectively. PMID- 8191993 TI - Detection of recurrent hepatic metastases after partial hepatectomy: value of CT combined with arterial portography. AB - OBJECTIVE: We did a retrospective study to evaluate the sensitivity of CT combined with arterial portography in detecting recurrent hepatic metastases after partial hepatectomy. MATERIALS AND METHODS: CT scans combined with arterial portography in 18 patients who had partial hepatectomy and suspected intrahepatic recurrence of metastases were retrospectively reviewed. Eleven of the patients had further surgery, and recurrent hepatic metastases were proved; seven patients were inoperable. The sensitivity of CT with arterial portography for detecting recurrent intrahepatic metastases was determined and correlated with intraoperative findings and findings on follow-up imaging studies in the 11 patients (with a total of 23 hepatic metastases) who had further surgery. RESULTS: Not one of the 18 CT examinations combined with arterial portography was compromised by inhomogeneous perfusion of contrast material in the portal vein. Of the 23 metastases that were found in the 11 patients who had further surgery, 21 (91%) were shown on CT with arterial portography. In two patients, CT with arterial portography showed two subcapsular hypoattenuating pseudolesions that were correctly identified as nontumorous perfusion defects, as confirmed by intraoperative findings and follow-up imaging studies. CONCLUSION: This study shows that postoperative CT with arterial portography is efficacious in the detection of intrahepatic recurrent metastases in patients who have had a partial hepatectomy. Furthermore, prior partial hepatectomy does not compromise the quality of this examination. PMID- 8191994 TI - Noninvasive imaging of the biliary tree before or after laparoscopic cholecystectomy: use of three-dimensional spiral CT cholangiography. AB - OBJECTIVE: The purpose of this study was to determine the feasibility of using three-dimensional spiral CT after IV administration of a cholangiographic agent for noninvasive detection of anatomic variations of the bile ducts and common bile duct stones before or after laparoscopic cholecystectomy. SUBJECTS AND METHODS: Three-dimensional spiral CT cholangiography was performed before laparoscopic cholecystectomy in 24 patients and after surgery in two patients who had recurrent symptoms. After slow infusion of 250 ml of iodipamide, spiral CT was performed. Three-dimensional images of the bile ducts and a secondary reformation through the long axis of the common bile duct were obtained. Visualization of the biliary tract was evaluated by two observers. Detection of anatomic variations and common bile duct stones was assessed in 19 patients for whom a gold standard (operative or retrograde cholangiogram) was available. RESULTS: In all 26 patients, the common bile duct and the confluence of the hepatic ducts were seen on three-dimensional spiral CT cholangiograms, and in 21 patients second- or higher-order branches were also seen. Seven patients had anatomic variations and two had common bile duct stones. These anomalies were proved by operative cholangiography in each case, except for a low junction of the cystic duct and a common bile duct stone, which were shown by retrograde cholangiography. Six of the seven anatomic variations were adequately detected with spiral CT cholangiography, as were the two cases of common bile duct stones. CONCLUSION: Three-dimensional spiral CT cholangiography is a feasible method for noninvasive detection of biliary anatomic variations and common bile duct stones before or after laparoscopic cholecystectomy. PMID- 8191995 TI - Variations in venous and segmental anatomy of the liver: two- and three dimensional MR imaging in healthy volunteers. AB - OBJECTIVE: The purpose of this study was to use two- and three-dimensional analysis of thin-slice MR imaging data to study the anatomic variations in the segmental anatomy of the liver. It is important to recognize these anatomic variations in order to ensure accurate localization of hepatic lesions and preoperative delineation of resection planes. SUBJECTS AND METHODS: T1-weighted MR images of contiguous 4-mm sections were obtained in 10 healthy subjects. We measured the orientations of external and internal hepatic landmarks that indicated segmental boundaries and created three-dimensional renderings of hepatic veins, intrahepatic portal branches, liver surface, and gallbladder. RESULTS: Variations in the portal branching pattern were seen in eight of 10 subjects. Most variations occurred in the right hemiliver and consisted of the absence of a right portal trunk or the presence of accessory portal branches. The division between right anterior and right posterior segments was inclined posteriorly (average, 31.2 degrees) relative to the right hepatic vein. The landmarks indicating the position of the umbilical fissure showed marked variability. Only two of 10 subjects had three hepatic veins, with the left and middle veins sharing a common trunk. In the remaining eight subjects, nine accessory veins were present: three left, one middle, and five right. CONCLUSION: Planes of resection in liver surgery are largely determined by the precise position of tumor relative to the individual segmental anatomy. Consequently, localization of liver lesions and preoperative delineation of resection planes requires consideration of the significant anatomic variations in the segmental anatomy of the liver. These anatomic variations can be depicted on two- and three dimensional displays of T1-weighted MR images of contiguous 4-mm sections. PMID- 8191996 TI - Septa in the liver of patients with chronic hepatic schistosomiasis japonica: MR appearance. AB - OBJECTIVE: Chronic hepatic schistosomiasis japonica is a disorder characterized by broad fibrous septa in the liver. The ability to recognize these septa on MR images might enable distinction of this lesion from other cirrhotic disorders. The purpose of this study was to analyze the MR appearance of these septa. MATERIALS AND METHODS: MR images of 18 patients who had typical calcifications of hepatic septa on CT scans were reviewed. The diagnosis was proved by biopsy in six patients. In the remaining 12, stool examinations were positive for schistosomiasis. T1-weighted MR images and T2-weighted and intermediate (long repetition time and short echo time) MR images acquired with the use of gradient moment nulling were obtained in all 18 patients. In eight of 18 patients, additional T2-weighted and intermediate images were obtained without gradient moment nulling. Fifteen patients had contrast-enhanced T1-weighted images. The presence of abnormal MR signal and its intensity at sites corresponding to the septa seen on CT scans were studied. RESULTS: MR images showed the septa as linear abnormalities frequently seen in the subdiaphragmatic portion of the right lobe of the liver. On T1-weighted images, septa had low signal intensity and were identified in nine of 18 patients. On T2-weighted images obtained with gradient moment nulling, septa had high signal intensity and were seen in 13 of 18 patients. On T2-weighted images obtained without gradient-moment nulling, the septa had primarily low signal intensity and were seen in five of eight patients. On intermediate MR images obtained with gradient-moment nulling, the septa had primarily high signal intensity and were seen in nine of 18 patients. On intermediate images obtained without gradient-moment nulling, the septa had primarily low signal intensity and were seen in four of eight patients. In nine of 15 patients, septa were visualized as high-signal-intensity lesions on contrast-enhanced T1-weighted images. In 14 of 18 patients, the septa were detected in one or more sequences. CONCLUSION: Our experience suggests that MR imaging in patients with chronic schistosomiasis of the liver depicts the morphologic features of hepatic septa. MR signal characteristics of septa are not unique, but use of gradient-moment nulling alters the signal intensity of septa, similar to that of blood vessels, on intermediate and T2-weighted images. PMID- 8191997 TI - Serous cystadenoma of the pancreas with a metachronous adenocarcinoma. PMID- 8191998 TI - Sonography of ovarian masses: poor sensitivity of resistive index for identifying malignant lesions. AB - OBJECTIVE: Current research suggests that the resistive index of adnexal masses is a sensitive measure for distinguishing between benign and malignant ovarian masses. We devised a study to determine how morphologic findings on sonograms compare with the resistive index of benign and malignant lesions. SUBJECTS AND METHODS: Pelvic sonograms were obtained in 34 women with 36 adnexal masses that were likely neoplastic or non-self-limiting (such as an endometrioma). Transabdominal and transvaginal sonograms were obtained, and the resistive index was calculated. A threshold resistive index of 0.4 was used to differentiate benign from malignant lesions. Masses were characterized prospectively as probably benign or possibly malignant on the basis of their sonographic appearance. Pathologic proof was obtained for 35 masses, and one mass was diagnosed on the basis of CT findings. RESULTS: Seventeen lesions were deemed probably benign, and pathologic examination showed that all 17 were benign. The resistive index was greater than 0.4 in 14 of these 17 cases. Nineteen lesions were characterized as possibly malignant. On pathologic examination, six were benign neoplasms, five were nonneoplastic masses, and eight were malignant neoplasms. The resistive index was greater than 0.4 in 10 of the 11 benign lesions. It was less than 0.4 in only two of the eight lesions that were classified as malignant on the basis of both morphologic and pathologic findings. CONCLUSION: Sonography is sensitive but not specific for distinguishing between benign and malignant ovarian neoplasms. Although use of the resistive index might improve specificity in the assessment of possibly malignant lesions, reliance on this parameter is potentially misleading, as six of eight malignant lesions in this series were miscategorized on the basis of their resistive index. PMID- 8191999 TI - The power of positive press. PMID- 8192000 TI - Renal parenchymal abnormalities associated with renal vein thrombosis: correlation between MR imaging and pathologic findings in rabbits. AB - OBJECTIVE: The purpose of this study was to correlate abnormalities of the renal parenchyma seen on MR images with pathologic findings in rabbits with acute thrombosis of the renal vein. MATERIALS AND METHODS: MR images were obtained in 21 rabbits before and 1 hr to 2 weeks after ligation of the renal vein. MR findings were correlated with pathologic findings. RESULTS: The cross-sectional area of the kidney was 1.7, 1.8, 1.9, 2.2, 1.3, and 1.0 times of its initial size at 1 hr, 3 hr, 1 day, 3 days, 1 week, and 2 weeks, respectively, after ligation of the renal vein. Corticomedullary contrast on T1-weighted images decreased persistently from 1 hr to 2 weeks after ligation. Between 1 hr and 1 week after ligation, T2-weighted images showed a layer with low signal intensity that was correlated with medullary congestion and hemorrhage on pathologic specimens. CONCLUSION: MR images show a layer with low signal intensity in the renal medulla that probably represents medullary congestion and hemorrhage of the kidney in rabbits with acute thrombosis of the renal vein. PMID- 8192001 TI - Intrarenal arterial Doppler sonography in the detection of renal vein thrombosis of the native kidney. AB - OBJECTIVE: Previous studies of transplant kidneys and recent reports on native kidneys have suggested intrarenal arterial Doppler findings can be helpful in the noninvasive workup of renal vein thrombosis. We used arterial Doppler sonography to evaluate cases of possible acute renal vein thrombosis in native kidneys that had equivocal results on standard Doppler analysis of the renal vein. MATERIALS AND METHODS: Twenty native kidneys in 12 patients with clinical findings suggestive of acute renal vein thrombosis had Doppler studies of the main renal vein that failed to show normal flow. In all 20 kidneys, duplex Doppler study of arcuate/interlobar intrarenal arteries was done and the resistive index was determined. The Doppler findings were compared with subsequent findings on either renal venograms (n = 11) or MR images (n = 9), which served as the reference "gold" standards. RESULTS: The prevalence of renal vein thrombosis was 25% (5/20). Ten kidneys had very abnormal findings on arterial Doppler studies (absent or reversed end-diastolic flow), but only two of these were proved to have renal vein thrombosis. In six other kidneys, end-diastolic flow was identified but the resistive index was still elevated (> or = 0.70), and only one of these kidneys was proved to have renal vein thrombosis. Four kidneys had normal arterial Doppler studies, and 50% (two) of these were proved to have renal vein thrombosis. When absent or reversed end-diastolic flow was used as a sign of renal vein thrombosis, intrarenal arterial Doppler analysis had a sensitivity of 40% (2/5) and a specificity of 47% (7/15). CONCLUSION: Unlike the reported experience in transplanted kidneys, intrarenal arterial Doppler analysis is neither sensitive nor specific for renal vein thrombosis in native kidneys. An intrarenal arterial Doppler study with normal findings should not prevent further workup if Doppler findings in the renal vein are equivocal, nor should absent or reversed end-diastolic arterial signals be considered highly suggestive of renal vein thrombosis. PMID- 8192002 TI - Doppler evaluation of renal artery stenosis: interobserver agreement in the interpretation of waveform morphology. AB - OBJECTIVE: Analysis of Doppler waveform morphology for features of the tardus parvus phenomenon has been promoted as a useful and accurate means for detecting renal artery stenosis. The purpose of this study was to examine and quantify the interobserver agreement of such an analysis and to determine if interobserver differences limit the value of this approach for predicting renal artery stenosis. SUBJECTS AND METHODS: Four observers independently categorized renal artery waveforms of 47 patients (94 kidneys) clinically selected for renovascular hypertension. Waveforms were classified into five categories based on the presence and severity of tardus-parvus changes in the systolic upstroke and early systolic peak. This categorization was then compared with angiographic findings, and the results were analyzed with receiver-operating-characteristic curves. Kappa statistics and agreement tables were computed to evaluate interobserver agreement. RESULTS: Interobserver agreement in the waveform analysis for the four interpreters was statistically significant (p < 0.001). The receiver-operating characteristic areas produced by the observers indicated, however, that such waveform classification was not strongly predictive of renal artery stenosis. CONCLUSION: We conclude that substantial agreement in the interpretation of waveform morphology can be obtained between independent observers, and that such differences that do exist do not preclude the use of the pattern-recognition approach to waveform analysis. Even so, the specific application of this strategy to the waveform contours of early systole was not successful in predicting the presence or severity of renal artery stenosis. PMID- 8192003 TI - Categorization of acromial shape: interobserver variability with MR imaging and conventional radiography. AB - OBJECTIVE: Our purpose was to determine interobserver variability in the interpretation of the shape of the acromion on sagittal oblique MR images and conventional radiographs. The shape of the acromion was defined according to a previously described classification scheme. MATERIALS AND METHODS: We reviewed 26 sets of sagittal oblique MR images and corresponding conventional Y- or outlet view radiographs of the shoulder. The shape of the acromion was graded for each study independently by four reviewers. Interobserver agreement was measured by using the kappa statistic. Analysis of variance and the chi 2-test were used for univariate analysis. RESULTS: The acromion was interpreted most often as being curved. The observers scored 9% of MR images and 28% of conventional radiographs as nondiagnostic (p < .001) (41% of transscapular Y views and 3% of supraspinatus outlet views were also considered nondiagnostic [p < .0001]). Kappa values were .23 for MR images and .43 for conventional radiographs. Variability in interpretation between techniques when controlled for observer was not statistically significant. CONCLUSION: Although sagittal oblique MR images were significantly more likely than conventional radiographs to be considered diagnostic by observers, interobserver agreement for MR examinations was poor. There was moderate agreement with conventional radiographs. This calls into question the usefulness of the previous system of interpretation and suggests that it might be more applicable with conventional radiographs than with MR images. PMID- 8192004 TI - Vacuum phenomenon: a potential pitfall in the interpretation of gradient-recalled echo MR images of the shoulder. AB - OBJECTIVE: Axial gradient-recalled-echo (GRE) MR images of the shoulder obtained with the arm in external rotation may show a curvilinear or circular low-signal intensity focus in the superior portion of the glenohumeral joint space that is thought to represent gas within the joint (vacuum phenomenon). This study was performed to determine the prevalence of this finding on GRE MR images of the shoulder to confirm that it represents gas in the joint, and to establish criteria to distinguish it from a true abnormality. SUBJECTS AND METHODS: We reviewed all external-rotation GRE images of 45 consecutive patients and 10 volunteers for the presence of low-signal-intensity foci and joint effusion. These findings were correlated with findings on corresponding spin-echo and GRE images of the shoulder with the arm in neutral position. MR findings also were correlated with findings on plain radiographs (37 patients) and shoulder CT scans (three patients and five volunteers) and with results of arthroscopy (19 patients). RESULTS: In nine (20%) of 44 patients and in five (50%) of 10 volunteers, axial external-rotation GRE images showed curvilinear or circular low signal-intensity foci interposed between the opposing glenohumeral articular surfaces at the superior aspect of the glenohumeral joint that were not seen on MR images obtained with the arm in neutral position. In two of three patients and in all five volunteer subjects, CT scans of the shoulder showed a small focus of gas within the joint, corresponding in location to the intraarticular low-signal intensity focus seen on MR images. Joint effusions were seen on MR images of 15 patients, and none of these images showed intraarticular gas. CONCLUSION: Circular or linear areas of low signal intensity are frequently seen on GRE MR images of the shoulder obtained with external rotation of the arm and represent small foci of intraarticular gas (vacuum phenomenon). Awareness of this potential pitfall and an understanding of the characteristic appearance and location of this collection of intraarticular gas may help prevent misdiagnosis of intraarticular loose bodies or chondrocalcinosis. PMID- 8192005 TI - Complications of hip arthroplasty causing periprosthetic radiolucency on plain radiographs. AB - The technique of hip arthroplasty is at least 30 years old and currently is performed 120,000 times per year in the United States [1]. Changes in materials and surgical techniques have markedly decreased the prevalence of infection and aseptic loosening. At the same time, other complications such as stress shielding and aggressive granulomatosis have become increasingly important complications of joint replacement [2]. All four of these entities manifest radiographically as periprosthetic lucency (Fig. 1.). The purpose of this essay is to illustrate the plain film findings of each of these complications. PMID- 8192006 TI - Risk factors in the development of early renal cortical defects in children with urinary tract infection. AB - OBJECTIVE: Defects seen on early cortical scintigrams of the renal cortex in children with urinary tract infection may represent acute inflammatory change or established scar. The purpose of this study was to determine the relationship between these defects and age, sex, the presence and grade of vesicoureteral reflux, and infective organism in a cohort of children examined after their first proved urinary tract infection. SUBJECTS AND METHODS: We prospectively examined 193 consecutive patients less than 5 years old who were seen at the ambulatory pediatric department during a 3-year period and had a first proved urinary tract infection. Children with obstructed or solitary kidneys were excluded. All patients were imaged with scintigraphy of the renal cortex and radiographic voiding cystourethrography within 15 days of diagnosis. The association of age, sex, the presence and grade of vesicoureteral reflux, and infective organism with a defect (acute pyelonephritis or a renal scar) seen on a cortical renal scan was studied. RESULTS: The prevalence of cortical defects was greater in the kidneys of patients less than 2 years old (96/290, 33%) than in older children (16/96, 17%) and greater in those with vesicoureteral reflux (41/92, 45%) than in those without it (71/294, 24%). Vesicoureteral reflux was absent in 63% (71/112) of kidneys with a cortical defect. No association with sex or infective organism was established. As well as having a greater prevalence of cortical defects, 145 (75%) of the 193 urinary tract infections included in the study were in children less than 2 years old. The kidneys of these younger patients also had a greater severity and prevalence of vesicoureteral reflux (74/290, 26%) than did those of older children (18/96, 19%). CONCLUSION: Early cortical defects are associated with an age less than 2 years and vesicoureteral reflux. However, the association of early defects with the presence and grade of vesicoureteral reflux is confounded by the declining prevalence and severity of reflux with age. A significant proportion of cortical defects occur in the absence of vesicoureteral reflux, and the contribution of reflux to scar formation might be less than previously considered. PMID- 8192007 TI - Sequence and rate of bone marrow conversion in the femora of children as seen on MR imaging: are accepted standards accurate? AB - OBJECTIVE: The purpose of this study was to reassess the normal sequence and rate of marrow conversion in the femora of children as depicted on MR imaging. MATERIALS AND METHODS: We retrospectively analyzed 81 T1-weighted MR images of the femur for the appearance and distribution of hematopoietic (red) and fatty (yellow) marrow. Eighty-one children 2 days to 15 years old with no known bone marrow abnormalities were divided into four age groups. The signal intensity and homogeneity of the marrow in the proximal epiphysis, proximal metaphysis, diaphysis, distal metaphysis, distal epiphysis, and greater trochanter were compared with the signal intensity and homogeneity of surrounding muscle and fat and graded by two observers. In select cases, region-of-interest measurements of marrow, subcutaneous fat, and muscle were obtained to validate the visual grading system. RESULTS: Conversion of hematopoietic to fatty marrow in the femur followed a well-defined sequence, occurring first in the proximal and distal epiphyses, followed by the diaphysis, distal metaphysis, and then the proximal metaphysis. Although high-signal-intensity fatty marrow could be seen within the femoral diaphysis as early as 3 months of age, fatty marrow with various degrees of heterogeneity was routinely seen in this region by 12 months of age. After 5 years of age, the femoral diaphysis showed homogeneous high signal intensity. These findings are in contrast to previously published data that describe homogeneous red marrow within the femoral diaphysis during the first year of life and homogeneous yellow marrow visualized by 10 years of age. CONCLUSION: The normal age-related sequence of femoral marrow conversion we saw on MR images conforms to the sequence described in previously published reports, but this transformation, particularly in the diaphysis, occurs significantly earlier in life than has been previously reported. This discrepancy might be explained partially by the sensitivity of signal intensity in the femoral marrow to alterations in window and level settings. PMID- 8192008 TI - Abnormal odontogenesis in children treated with radiation and chemotherapy: imaging findings. AB - Contemporary oncotherapy has improved survival of children with malignant diseases, but chemotherapy and radiotherapy also have deleterious effects. This essay illustrates the effects of chemotherapy and radiotherapy on dentition in children and adolescents. The illustrated abnormalities were seen on panoramic radiographs obtained before, during, and after treatment. Included are examples of hypodontia (partial anodontia), microdontia, altered eruption patterns, and root stunting. Comparison is made with normal dental development (Fig. 1). PMID- 8192009 TI - Germinomas of the basal ganglia and thalamus: MR findings and a comparison between MR and CT. AB - OBJECTIVE: The purpose of this study was to describe the MR imaging appearance of germinomas in the basal ganglia and thalamus and to compare the MR findings with CT findings. MATERIALS AND METHODS: Eleven MR studies of 10 patients with pathologically proved germinomas in the basal ganglia or thalamus were retrospectively reviewed. In nine of the 10, the MR findings were compared with CT findings. All patients were male, and all except one were in their second decade of life. All the tumors were located in paraventricular areas. RESULTS: Most of the tumors were 4-7 cm in diameter. MR images showed that the tumors were mostly cystic in five patients, mostly solid with cystic components in four, and solid without cystic components in one. The solid portion mostly was isointense relative to the cerebral cortex for all MR pulse sequences. The cystic portion was hyperintense relative to CSF on T1- and T2-weighted images. MR images showed intratumoral hemorrhage in seven patients. It appeared as an area of hyperintensity on T1- and T2-weighted images in five patients and as a fluid fluid level with marked hypointensity on T2-weighted images in two. Hemorrhage was not visualized on CT scans in any patient. Flecked or amorphous calcifications visualized on CT scans in two patients were hardly detectable on MR images. Peritumoral edema was usually minimal. CT scans and MR images obtained after injection of contrast material both showed heterogeneous and dense enhancement in the solid portions of the tumors. CONCLUSION: MR images of germinoma in the basal ganglia and thalamus show a large paraventricular mass. Cystic areas, focal hemorrhages, and minimal surrounding edema are common. Unlike CT, MR imaging allows characterization of intratumoral hemorrhage. PMID- 8192010 TI - Intracranial extramedullary hematopoiesis: MR findings with pathologic correlation. PMID- 8192011 TI - Ulcerated plaques and focal aneurysms of iliac arteries: treatment with noncovered, self-expanding stents. AB - OBJECTIVE: We studied the value of noncovered, self-expanding stents for treatment of ulcerated plaques and focal aneurysms of iliac arteries. MATERIALS AND METHODS: Seventeen patients with ulcerated plaques (n = 13) and aneurysms (n = 5) were treated with noncovered, self-expanding Wallstent endoprostheses. A total of 18 lesions were stented. The lesions were in the common iliac artery (n = 10), the external iliac artery (n = 3), or affected parts of both arteries (n = 5). Their mean length was 3.5 +/- 1.0 cm. All lesions were accompanied by stenosis of the affected arterial segment. RESULTS: Occlusion of ulcerations or aneurysms occurred immediately in three cases and thereafter in the remaining 15 cases, as shown by angiographic follow-up. Embolization did not occur. Follow-up revealed a 4-year cumulative patency of 82%, with reobstruction of the stent in three cases. CONCLUSION: Noncovered stents are a rational approach to treating circumscribed aneurysms and ulcerated plaques of the iliac arteries. The stent regularly smoothens the vessel wall by sealing the ulcerated area or aneurysm immediately or soon after stent placement. PMID- 8192012 TI - Three-dimensional models of the abdominal vasculature based on helical CT: usefulness in patients with pancreatic neoplasms. AB - Three-dimensional (3D) rendering of helical (spiral) CT data is used increasingly to show abnormalities of the vascular system [1]. Abdominal applications have focused mainly on the arterial system, but the portal venous system also can be depicted effectively with this technique. In patients with pancreaticobiliary neoplasms, axial display of helical CT images generally allows accurate staging of the lesion [2, 3]. Many surgeons, however, continue to request arteriography to specifically look for evidence of vascular encasement that would preclude surgery or vascular anomalies that would alter the surgical approach [4, 5]. The purpose of this essay is to illustrate the value of 3D rendering of CT data in providing useful information for surgical planning and showing the extent of vascular involvement by tumor. PMID- 8192013 TI - MR angiography of the carotid bifurcation: artifacts and limitations. AB - Although conventional angiography has traditionally been the preoperative study of choice before carotid endarterectomy, alternative noninvasive methods, particularly MR angiography, are being used increasingly for evaluation of the carotid bifurcation [1, 2]. In this essay, we illustrate the limitations of and artifacts associated with two-dimensional (2D) and three-dimensional (3D) time-of flight (TOF) MR angiography vs conventional angiography when assessing disease of the carotid bifurcation. PMID- 8192014 TI - Solo practice management: value of a computerized reporting system. AB - OBJECTIVE. A computerized reporting system based on keyed entry of acronyms and eponyms was developed to reduce transcription delays and speed report output for a solo radiology practice that covers several community hospitals in a large region. The purpose was to improve practice outcomes, quality assessments, continuing medical education, and billing efficiency. SYSTEM AND APPLICATIONS. Over a 10-year period, problems in accurate reporting, transcription delays, slowed report deliveries, and incomplete or lost billings were described to computer programmers. These programmers composed 31,000 lines of computer code designed to address the problems. The resultant program was applied to 100,000 imaging procedures. Entry of commonly used clinical acronyms, eponyms, and other symbol strings chosen by the interpreting radiologist triggered the immediate printing of a report's text at the radiologist's desk. After the reports were proofread, electronically authenticated, and/or hand signed, they were sent to distant locales by facsimile transmission. During new case interpretations, potentially erroneous statements of fact or judgement were prevented by enabling the interpreter to instantly review old reports, informative elements of a patient's history, and pertinent medical literature, all of which was placed in various caches of the computer's memory. Billing labor was reduced by automatically providing the number identifying each procedure and the diagnoses made during image interpretation. OPERATION. The acronym/eponym-based reporting system was time- and cost-effective. The new system reduced typing strokes by 84%, and reports were generated in 1 min, while the studies were being interpreted. With the retrieval and monitoring techniques operating on old, stored information, new reporting errors, as well as some diagnostic oversights, were reduced by 50%. Counting the acronyms and symbols representing imaging quality and technical problems showed an 11% mistake rate. Modem transmission of automatically included current procedural terms and disease classification numbers reduced billing labor by 50% and reduced lost charges to zero. The same messaging mechanism of the program sent the text of interpretations to remote clinics and hospitals a few minutes after the radiologist's interpretation was made. CONCLUSION. My experience suggests that a computerized reporting and messaging system based on acronyms and eponyms is a time- and cost-effective technique for managing a solo radiology practice. By using a programmable relational data base, one can modify the system to include educational, quality improvement, and billing functions. PMID- 8192015 TI - A simplified HyperCard data base for patient management in an interventional practice: experience with more than 4000 cases. AB - OBJECTIVE: Tracking of interventional radiology procedures is essential for patients' care, follow-up, and quality management, as well as for fellowship training and accreditation. Computer data-base systems that require time consuming data entry are difficult to use in a practice that performs 1500 abdominal interventional procedures each year while concurrently doing diagnostic imaging. We proposed that a data base updated with data from existing sources and furnishing information used daily in patient management could be maintained by the radiologists it serves. MATERIALS AND METHODS: We developed a data base to track abdominal interventional radiology cases by using the HyperCard application program running on Macintosh personal computers. For each procedure, one card is entered into the Current Cases stack, which prints a daily log including new patients, those with management issues, and pending biopsy results. Cards for inactive patients are automatically compressed and transferred to a second stack for permanent archive. The latter can be queried to identify individual patients, to list complications, and for research. RESULTS: In continuous use for 3 years, the system has logged 4322 procedures in 2394 patients. Ninety percent of data entry is by a secretary. The daily log serves as the focus for the case conference at the close of work, when errors are corrected and specific comments entered. Three independent searches for specific types of procedures have failed to identify excluded cases. CONCLUSION: Easy data entry and error correction, together with useful information provided daily by the data base, are features of the system that promote its consistent use. PMID- 8192017 TI - Gastrointestinal case of the day. Hepatic and pulmonary accumulation of amiodarone. PMID- 8192016 TI - Gastrointestinal case of the day. Suprahepatic gallbladder. PMID- 8192018 TI - Gastrointestinal case of the day. Pancreatic abscess due to Pneumocystis carinii. PMID- 8192019 TI - Gastrointestinal case of the day. Acute nontraumatic rhabdomyolysis. PMID- 8192020 TI - Genitourinary case of the day. Exercise-induced acute renal failure. PMID- 8192021 TI - Genitourinary case of the day. Lymphoma of the ureter. PMID- 8192022 TI - Genitourinary case of the day. Autosomal dominant polycystic kidney disease complicated by thoracic aortic dissection. PMID- 8192023 TI - Genitourinary case of the day. Retroperitoneal fibrosis. PMID- 8192024 TI - Women's health case of the day. Uterine arteriovenous malformation. PMID- 8192025 TI - Women's health case of the day. Regressing arterial calcifications in breast. PMID- 8192026 TI - Women's health case of the day. Unsuspected uterine didelphia. PMID- 8192027 TI - Women's health case of the day. Obstruction of left innominate vein with diffuse edema in left breast mimicking inflammatory carcinoma. PMID- 8192028 TI - Musculoskeletal case of the day. Extraskeletal osteosarcoma of the thigh. PMID- 8192029 TI - Musculoskeletal case of the day. Intramuscular hemangioma of the thigh. PMID- 8192030 TI - Musculoskeletal case of the day. Chondrosarcoma of the pelvis. PMID- 8192032 TI - Pediatric radiology case of the day. Hereditary hemorrhagic telangiectasia (Osler Weber-Rendu disease). PMID- 8192031 TI - Musculoskeletal case of the day. Osteosarcomatosis. PMID- 8192033 TI - Pediatric radiology case of the day. Tuberous sclerosis. PMID- 8192034 TI - Pediatric radiology case of the day. Eosinophilic granuloma. PMID- 8192035 TI - Pediatric radiology case of the day. Noncalcified retinoblastoma. PMID- 8192036 TI - Neuroradiology case of the day. Medulloblastoma. PMID- 8192038 TI - Neuroradiology case of the day. Malignant melanoma. PMID- 8192037 TI - Neuroradiology case of the day. Dural arteriovenous malformation. PMID- 8192039 TI - Neuroradiology case of the day. Moyamoya disease. PMID- 8192040 TI - 1993 ACR Intersociety Commission summit meeting: health care system reform- opportunities and exigencies. PMID- 8192041 TI - Does MR imaging have any known effects on the developing fetus? PMID- 8192042 TI - Since the advent of CT scanning, what role does the contrast enema examination play in the diagnosis of acute diverticulitis? PMID- 8192043 TI - Wrist arthrogram after previous anaphylactoid reaction to contrast medium. PMID- 8192044 TI - Is there a role for wrist arthrography now that MR imaging is generally available? PMID- 8192045 TI - Is shoulder arthrography considered an acceptable alternative to MR imaging in the evaluation of rotator cuff tears? PMID- 8192046 TI - If a region of osteochondritis dissecans is identified on a radiographic examination of the knee, should an MR study be performed? PMID- 8192047 TI - Are there any specific advantages or disadvantages to using CT instead of sonography to guide interventional procedures? PMID- 8192048 TI - How safe is the use of platinum microcoils for embolization of small mesenteric arteries in patients with gastrointestinal bleeding? PMID- 8192049 TI - Injury due to extravasation of nonionic contrast material. PMID- 8192050 TI - Mediastinal lymphadenopathy in mycoplasmal pneumonia. PMID- 8192051 TI - Large-core breast biopsy to obtain tissue for tumor markers in breast lymphoma. PMID- 8192052 TI - Left-sided paraduodenal internal hernia containing sigmoid colon: diagnosis based on findings on barium examinations. PMID- 8192053 TI - Delayed enhancement of ascitic fluid on CT scans. PMID- 8192054 TI - Cystic prostatic carcinoma. PMID- 8192055 TI - MR diagnosis of recurrent meniscal tears: how soon we forget. PMID- 8192056 TI - Ganglion cysts of the cruciate ligaments of the knee: recognition on MR images and CT-guided aspiration. PMID- 8192057 TI - Use of color Doppler sonography for detection of thyroid nodules. PMID- 8192058 TI - CT and MR findings in familial erythrophagocytic lymphohistiocytosis. PMID- 8192059 TI - Varix of the eyelid: a unique CT finding. PMID- 8192060 TI - Quantitative CT data base for microcomputers. PMID- 8192061 TI - Spiral vs helical: a matter of precision. PMID- 8192062 TI - Dyke Award paper. MR of wallerian degeneration in the feline visual system: characterization by magnetization transfer rate with histopathologic correlation. AB - PURPOSE: To examine the utility of measuring magnetization transfer ratio for for delineating the dynamic changes of wallerian degeneration which occur after controlled injury in a feline model in which anatomic pathways are well understood. METHODS: Using standard neurosurgical techniques, discrete lesions were made to ablate the visual cortex. Gradient imaging was performed serially at 1.5 T, with and without a saturation pulse to create a magnetization transfer effect. At varying intervals, the animals were killed for histologic analysis. RESULTS: Within the first 2 weeks there is a statistically significant increase in magnetization transfer ratio relative to the control hemisphere within the white matter connections between the lateral geniculate nucleus and the visual cortex at a time when no effects are visually detectable on spin-echo images. Between 16 and 28 days, this reverses to a decrease in magnetization transfer ratio in both the lateral geniculate nucleus itself and the adjacent superolateral white matter. More remote white matter tracts remained stable, without significant change. CONCLUSIONS: Magnetization transfer ratio seems to be more sensitive for early detection of degeneration than conventional spin-echo imaging. Moreover, temporal changes in magnetization transfer ratio seem to correspond well with known histologic phases of wallerian degeneration. PMID- 8192063 TI - Acute intracranial hemorrhage secondary to thrombocytopenia: CT appearances unaffected by absence of clot retraction. AB - PURPOSE: To describe the in vivo CT appearance of acute intracerebral blood clots formed from anemic platelet-depleted blood. METHODS: Three patients with intracerebral hemorrhage secondary only to thrombocytopenia were examined with CT within 2 1/2 hours after the onset of clinical symptoms. RESULTS: There were no unusual CT features found in the intracerebral hemorrhages of patients with only thrombocytopenia. Specifically, a hyperdense zone(s) surrounded by areas of decreased density was identified. CONCLUSION: Clot retraction (which cannot occur in patients with severe thrombocytopenia) is not necessary for the CT appearance of acute intracerebral hemorrhage. PMID- 8192064 TI - Sensitivity and specificity of fluid-blood levels for coagulopathy in acute intracerebral hematomas. AB - PURPOSE: To characterize the imaging features of intracerebral hemorrhages in coagulopathies that alter prothrombin time or partial thromboplastin time. METHODS: A fluid-blood level was defined as a horizontal interface between hypodense bloody serum layered above hyperdense settled blood. The prevalence of fluid-blood levels in acute intracerebral hemorrhages was determined on third generation CT scans in 32 patients with elevation in prothrombin time or partial thromboplastin time. This was compared with the frequency of fluid-blood levels in 185 patients with intracerebral hemorrhage in which there was no laboratory evidence of coagulopathy. RESULTS: The probability of finding a fluid-blood level in an intracerebral hemorrhage of a patient with abnormal prothrombin time or partial thromboplastin time was 59% (sensitivity). The probability that there will be no fluid-blood level in a patient with a normal prothrombin time and partial thromboplastin time was 98% (specificity). CONCLUSION: Fluid-blood levels in acute intracerebral hemorrhage are moderately sensitive to the presence of coagulopathy (ie, abnormal prothrombin time and partial thromboplastin time) and highly specific for this condition. Thus, an intracerebral hemorrhage with a fluid-blood level should prompt a thorough search for coagulopathy because early treatment of this condition may improve the 40% mortality in these patients. Caution should be used to distinguish the horizontal interface of a fluid-blood level from a clot with a flat top. A decubitus CT is useful in these rare instances. PMID- 8192065 TI - MR volume segmentation of gray matter and white matter using manual thresholding: dependence on image brightness. AB - PURPOSE: To describe a quantitative MR imaging segmentation method for determination of the volume of cerebrospinal fluid, gray matter, and white matter in living human brain, and to determine the method's reliability. METHODS: We developed a computer method that allows rapid, user-friendly determination of cerebrospinal fluid, gray matter, and white matter volumes in a reliable manner, both globally and regionally. This method was applied to a large control population (N = 57). RESULTS: Initially, image brightness had a strong correlation with the gray-white ratio (r = .78). Bright images tended to overestimate, dim images to underestimate gray matter volumes. This artifact was corrected for by offsetting each image to an approximately equal brightness. After brightness correction, gray-white ratio was correlated with age (r = -.35). The age-dependent gray-white ratio was similar to that for the same age range in a prior neuropathology report. Interrater reliability was high (.93 intraclass correlation coefficient). CONCLUSIONS: The method described here for gray matter, white matter, and cerebrospinal fluid volume calculation is reliable and valid. A correction method for an artifact related to image brightness was developed. PMID- 8192066 TI - Diffusional anisotropy of the human brain assessed with diffusion-weighted MR: relation with normal brain development and aging. AB - PURPOSE: To analyze diffusional anisotropy in frontal and occipital white matter of human brain quantitatively as a function of age by using diffusion-weighted MR imaging. METHODS: Ten neonates (< 1 month), 13 infants (1-10 months), 9 children (1-11 years), and 16 adults (20-79 years) were examined. After taking axial spin echo images of the brain, diffusion-sensitive gradients were added parallel or perpendicular to the orientation of nerve fibers. The apparent diffusion coefficient parallel to the nerve fibers (0) and that perpendicular to the fibers (90) were computed. The anisotropic ratio (90/0) was calculated as a function of age. RESULTS: Anisotropic ratios of frontal white matter were significantly larger in neonates as compared with infants, children, or adults. The ratios showed rapid decrease until 6 months and thereafter were identical in all subjects. In the occipital lobe, the ratios were also greater in neonates, but the differences from other age groups were not so prominent as in the frontal lobe. Comparing anisotropic ratios between frontal and occipital lobes, a significant difference was observed only in neonates. CONCLUSIONS: Diffusion weighted images demonstrated that the myelination process starts earlier in the occipital lobe than in the frontal lobe. The changes of diffusional anisotropy in white matter are completed within 6 months after birth. Diffusion-weighted imaging provides earlier detection of brain myelination compared with the conventional T1- and T2-weighted images. PMID- 8192067 TI - The role of early MR in the evaluation of the term infant with seizures. AB - PURPOSE: To define the role of MR in evaluating term neonates with seizures the most common clinical manifestation of cerebral injury in neonates. METHODS: Fifteen term infants with seizures underwent MR imaging. The presence and pattern of MR findings were compared with clinical markers of perinatal distress, cause of cerebral injury, and short-term neurologic outcome. RESULTS: Seizures were caused by hypoxic-ischemic encephalopathy in three patients, bacterial meningitis in three, and prenatal cocaine exposure in one. Nine patients had no identifiable risk factors. By MR, five patients had focal ischemic injury of the cerebral hemispheres and/or basal ganglia and brain stem. Six patients had diffuse cerebral edema: of these, five had basal ganglia edema; one had brain stem edema. One patient had superior sagittal sinus thrombosis with venous infarcts. Three patients had normal MR studies. There was no correlation between markers of perinatal distress, risk factors for seizures, and presence or pattern of MR findings. There was some correlation between MR findings of diffuse cerebral injury and neurologic outcome, and between MR findings of basal ganglia and brain stem abnormalities and neurologic outcome; these findings correlated with spasticity and hemiplegia at 6 to 24 months follow-up. CONCLUSION: The presence or pattern of MR findings does not appear to correlate with with clinical signs of perinatal distress or presumed causes of perinatal cerebral injury. Further investigation is needed to identify prospectively neonates with seizures who are at risk for significant neurologic morbidity. PMID- 8192068 TI - Congenital defects of the posterior arch of the atlas: a report of seven cases including an affected mother and son. AB - PURPOSE: To describe our experience with congenital anomalies of the posterior arch of the atlas, with a review and classification of these defects and a note on their clinical significance. METHODS: We report six children and one adult, the mother of one of the children, with an anomalous posterior arch of the atlas. The diagnosis was made on lateral films of the neck. Three patients also had axial CT of the cervical spine. RESULTS: The anomalies encountered in the seven patients were absence of the posterior arch of the atlas (four patients), bilateral clefts (two patients), and unilateral cleft (one patient). In three patients the anomaly was discovered as an incidental asymptomatic finding; three other patients presented with transient neck pain or transient neurologic symptoms after head and neck trauma, and one patient (an adult woman) described neck symptoms of 1-year duration. CONCLUSIONS: On the basis of these seven cases we conclude that congenital defects of the posterior arch of the atlas may be discovered as incidental asymptomatic findings, but symptoms occurring after trauma to the head and neck or spontaneously also may be encountered. PMID- 8192069 TI - Transient monocular blindness in carotid occlusion testing. AB - A patient developed monocular blindness 23 minutes into a temporary balloon occlusion test of the carotid artery, on the side being tested. His vision returned to normal 1 minute after the balloon was deflated. The authors emphasize the importance of complete frequent neurologic examination during this kind of test. PMID- 8192070 TI - Ocular ischemic syndrome during carotid balloon occlusion testing. AB - The use of a double-lumen balloon catheter for temporary occlusion testing of the internal carotid artery permits simultaneous perfusion of the distal internal carotid artery (and ophthalmic artery) with heparinized saline. If saline is infused too rapidly, the result may be total or partial replacement of oxygenated blood within the ophthalmic artery. This replacement may produce the signs and symptoms of ocular ischemic syndrome. These include ipsilateral orbital pain and progressive uniocular visual loss. Simple technical adjustments in the performance of the occlusion test can prevent the development of this syndrome. Failure to recognize the cause of the observed visual loss may produce the false impression of a positive occlusion test or may falsely suggest that a thromboembolic complication has occurred. Awareness of the occurrence of this syndrome should prevent confusion concerning the predictive result of provocative carotid occlusion testing. PMID- 8192071 TI - A clinical and neuropathologic study of silk suture as an embolic agent for brain arteriovenous malformations. AB - PURPOSE: To evaluate the safety and efficacy of silk suture as an agent for preoperative embolization of cerebral arteriovenous malformations. METHODS: Clinical and histopathologic results were analyzed in six patients who underwent embolization of cerebral arteriovenous malformations using silk suture in combination with other agents. RESULTS: Three of the patients treated with silk hemorrhaged after embolization, and two of these patients died. Neuropathologic analysis of four patients showed acute perivascular inflammation, sometimes quite severe. CONCLUSIONS: The inflammatory response to silk may explain its effectiveness in producing vascular occlusion. However, a fulminate vasculitis theoretically can predispose to delayed hemorrhage. Other problems with silk include the pressure required to inject the agent and the inability to determine the final site of deposition of the silk. Although other embolic agents may share some of these potential difficulties, we feel that the disadvantages outweigh the advantages of silk as an embolic agent. PMID- 8192072 TI - Anatomic moment. The septal area. PMID- 8192073 TI - MR appearance of Virchow-Robin spaces along lenticulostriate arteries: spin-echo and two-dimensional fast low-angle shot imaging. AB - PURPOSE: To delineate the appearance of normal Virchow-Robin spaces on routine spin-echo images and demonstrate the lenticulostriate arteries within them with a flow-sensitive fast low-angle shot (FLASH) pulse sequence. METHODS: Seventy subjects, free of cerebrovascular diseases and other neurologic disorders, ranging in age from 1 to 75 years, were examined. On a 1.5-T MR system, axial spin-echo images of 5 mm thickness were obtained in all subjects. In 45 of 70 subjects axial two-dimensional FLASH images of 3 mm thickness were continuously imaged. RESULTS: On T1- and spin density-weighted images Virchow-Robin spaces were detected as small foci of cerebrospinal fluid intensity around the anterior commissure in all subjects (100%), and in the basal ganglia at the level of the foramen of Monro in 40 (57%). T2-weighted images equally showed Virchow-Robin spaces around the anterior commissure but were less sensitive than T1- and spin density weighted images at the level of the foramen of Monro (14%). Virchow-Robin spaces identified on T2-weighted images should be isointense with cerebrospinal fluid. However, one or two spaces in 11 younger subjects were hypointense relative to adjacent brain tissue. On FLASH images most Virchow-Robin spaces identified on spin-echo images were delineated as high-intensity foci, corresponding to lenticulostriate arteries. CONCLUSIONS: Normal Virchow-Robin spaces along the lenticulostriate arteries are frequently detected on spin-echo images. Their appearance, affected by the flow of associated lenticulostriate arteries, varies from hyper- to hypointensity to brain tissue on T2-weighted images. The two-dimensional FLASH sequence can demonstrate the flow of the arteries, thereby helping confirm that these are truly Virchow-Robin spaces. PMID- 8192074 TI - Skull-base foramina of the middle cranial fossa: reassessment of normal variation with high-resolution CT. AB - PURPOSE: To evaluate by means of high-resolution CT the anatomic variations of the middle cranial fossa foramen. METHODS: We examined 123 CT studies of the temporal bone in patients with no evidence of disease that might alter foraminal anatomy. A checklist of known variants and suspected structures was used as each case was systematically examined for the presence or absence of these foramina; variations in size, shape, and location; and relationship of structures to each other. Inclusion criteria were established to eliminate error. RESULTS: The foramen rotundum had a constant appearance. We identified the inferior rotundal canal in 16% of patients and the lateral rotundal canal in 8%. The foramen of Vesalius was present, at least unilaterally, in 80% of our cases. Asymmetry of the foramen of Vesalius did not indicate disease in our patient group. We did not find an inverse relationship between the size of the foramen of Vesalius and that of the ipsilateral foramen ovale. We found variations in the size and shape of the foramen ovale and its confluence with the foramen spinosum (n = 2) and the foramen of Vesalius (n = 8). We did not find an inverse relationship between the size of the foramen ovale and that of the foramen spinosum. The canaliculus innominatus for the lesser superficial petrosal nerve was identified in 16.3% of our patients. Variations of the foramen spinosum that we found include a medial bony defect (26.8%) and absence (3.2%). CONCLUSION: Although it is unlikely that well-formed foramen will be misinterpreted as diseased, it is nonetheless important to recognize foraminal variants and associated neurovascular anatomy. PMID- 8192075 TI - Prevalence and percutaneous drainage of cysts of the sacral nerve root sheath (Tarlov cysts). AB - PURPOSE: To describe a percutaneous CT-guided method for drainage of perineurial (Tarlov) cysts, which are a cause of sciatica and low back pain, and to report the prevalence of these cysts within the population as detected by MR. METHODS: Five hundred sequential lumbosacral spine MRs were evaluated for the presence of a perineurial cyst. Using CT-guided percutaneous drainage techniques, seven cysts were drained in five symptomatic patients. RESULTS: Of the 500 sequential lumbosacral spine MRs, examinations from 23 patients showed perineurial cysts, a prevalence of 4.6%. Five patients (1%) were symptomatic from the cysts. After CT guided percutaneous drainage, instant pain relief lasted from 3 weeks to 6 months without the risk or cost of spine surgery. CONCLUSIONS: Lumbosacral perineurial cysts are common lesions that are usually asymptomatic but may cause pressure symptoms. Cyst puncture can alleviate the pain. Although the cysts repressurized and the patients' symptoms returned in most cases, this technique seems to be a quick and simple way of at least attaining a pain-free interval and possibly a complete cure as occurred in one patient in this study. PMID- 8192076 TI - MR of the spine in Guillain-Barre syndrome. AB - MR examination of the spine after injection of gadopentetate dimeglumine showed enhancement of the cauda equina in a case of Guillain-Barre syndrome. These MR observations may help confirm the diagnosis of Guillain-Barre syndrome. PMID- 8192077 TI - Lyme disease in childhood presenting as primary leptomeningeal enhancement without parenchymal findings on MR. AB - We report the MR appearance of a rare case of Lyme disease presenting as diffuse leptomeningeal enhancement in the absence of parenchymal lesions. In the appropriate clinical setting, one should consider Lyme disease in the differential diagnosis of meningeal enhancement. PMID- 8192078 TI - MR of primary extraosseous Ewing sarcoma. AB - We present MR imaging findings of a 15-year-old girl with a history of chronic back pain, proved by biopsy to be caused by primary extraosseous Ewing sarcoma, extending into the spinal epidural space. We also demonstrate the involvement of the adjacent structures and encroachment on the intervertebral foramina. PMID- 8192079 TI - Venous sinus occlusive disease: MR findings. AB - PURPOSE: To study MR patterns of venous sinus occlusive disease and to relate them to the underlying pathophysiology by comparing the appearance and pathophysiologic features of venous sinus occlusive disease with those of arterial ischemic disease. METHODS: The clinical data and MR examinations of 26 patients with venous sinus occlusive disease were retrospectively reviewed with special attention to mass effect, hemorrhage, and T2-weighted image abnormalities as well as to abnormal parenchymal, venous, or arterial enhancement after intravenous gadopentetate dimeglumine administration. Follow-up studies when available were evaluated for atrophy, infarction, chronic mass effect, and hemorrhage. RESULTS: Mass effect was present in 25 of 26 patients. Eleven of the 26 had mass effect without abnormal signal on T2-weighted images. Fifteen patients had abnormal signal on T2-weighted images, but this was much less extensive than the degree of brain swelling in all cases. No patient showed abnormal parenchymal or arterial enhancement. Abnormal venous enhancement was seen in 10 of 13 patients who had contrast-enhanced studies. Intraparenchymal hemorrhage was seen in nine patients with high signal on T2-weighted images predominantly peripheral to the hematoma in eight. Three overall MR patterns were observed in acute sinus thrombosis: 1) mass effect without associated abnormal signal on T2-weighted images, 2) mass effect with associated abnormal signal on T2-weighted images and/or ventricular dilatation that may be reversible, and 3) intraparenchymal hematoma with surrounding edema. CONCLUSION: MR findings of venous sinus occlusive disease are different from those of arterial ischemia and may reflect different underlying pathophysiology. In venous sinus occlusive disease, the breakdown of the blood-brain barrier (vasogenic edema and abnormal parenchymal enhancement) does not always occur, and brain swelling can persist up to 2 years with or without abnormal signal on T2-weighted images. Abnormal signal on T2-weighted images may be reversible and does not always indicate infarction. PMID- 8192080 TI - Diagnosing intracranial vasculitis: the roles of MR and angiography. AB - PURPOSE: To describe our experience with MR and angiography in diagnosing intracranial vasculitis and to test the hypothesis that MR can be used to screen for patients unlikely to have vasculitis. METHODS: Ninety-two patients who had angiography with "exclude vasculitis" as the indication or who had angiography and a clinical diagnosis of vasculitis were identified. Angiograms of all 92 patients and the MRs of the 70 patients who had both studies were reviewed. RESULTS: Eleven patients had intracranial vasculitis. Angiography showed characteristic changes in 8. MR, performed in 9 of 11 vasculitis cases, was significantly abnormal in all 9. Among 70 patients who had both studies, 19 had MR that was completely normal or showed only incidental findings. None of these 19 was diagnosed with vasculitis. The diagnostic yield of angiography performed to exclude vasculitis was only 6%. CONCLUSIONS: Evaluation for intracranial vasculitis should include MR. A negative MR excludes intracranial vasculitis more definitively than does a negative angiogram and makes the likelihood of finding vasculitis with angiography negligible. PMID- 8192081 TI - Primary angiitis of the central nervous system: unusual MR appearance. AB - The MR findings of a biopsy-proved case of primary angiitis of the central nervous system are described and compared with previously reported cases. Multiple punctate and linear areas of gadopentetate dimeglumine enhancement were present in the brain stem and white matter and appear to correspond to the inflammatory reaction of the small perforating vessels and perivascular tissues seen in the pathologic specimen. PMID- 8192082 TI - MR imaging of middle cerebral artery stenosis and occlusion: value of MR angiography. AB - PURPOSE: To investigate the effectiveness of MR angiography in conjunction with spin-echo imaging for evaluating vascular patency in patients with middle cerebral artery (MCA) stenosis or occlusion. METHODS: Seven patients with MCA stenosis or occlusion, verified with contrast angiography in five and correlated with transcranial Doppler sonography in two, were examined using two-dimensional and/or three-dimensional time-of-flight MR angiographic techniques as well as conventional spin-echo imaging. RESULTS: Of the seven patients, six demonstrated basal ganglionic and/or cortical infarct in the MCA territory. Except one case with minimal stenosis immediately distal to the MCA origin, all six cases with either severe stenosis or occlusion of the main trunk of the MCA showed the absence of normal flow voids using spin-echo imaging in the sylvian fissure on the affected side. However, it was not possible to discriminate between stenosis and occlusion. Although different mechanisms (ie, flow-induced spin dephasing for the 2-D technique and progressive spin saturation for the 3-D technique) were predominantly responsible for the loss of signal through the area of stenosis, both the 2-D and 3-D MR angiograms clearly depicted the compromised flow of the MCA: a focal discontinuity with decreased vessel caliber corresponded to stenosis, and nonvisualization of distal MCA branches represented occlusion. CONCLUSION: Either 2-D or 3-D time-of-flight MR angiography is a useful adjunct to conventional parenchymal spin-echo imaging for evaluating vascular patency in patients with MCA stenosis or occlusion, although it is important to recognize that each technique has a different basis for the loss of signal through the area of stenosis. PMID- 8192083 TI - Intraocular silicone oil: in vitro and in vivo MR and CT characteristics. AB - PURPOSE: To describe the CT and MR characteristics of intraocular silicone oil (polydimethylsiloxane), which is used with increasing frequency to treat complicated retinal detachments. METHODS: CT was performed on a silicone oil/water phantom and on a patient with retinal detachments secondary to cytomegalovirus retinitis, treated by bilateral intraocular injections of silicone oil. CT appearance and CT number of silicone oil were evaluated. Proton MR spectroscopy was performed with a 200-MHz spectrometer on a sample of polydimethylsiloxane within a tube of deuterated water. MR imaging was performed on a silicone oil/water phantom and on two patients with retinal detachments treated with silicone oil injection. RESULTS: Silicone oil is relatively radiodense; its CT attenuation is approximately 130 HU. On spectroscopy, silicone oil gave a single peak at 0.33 ppm. Relative to water silicone oil was hyperintense on T1-weighted images and hypointense on spin-density and T2 weighted images. Estimated T1 and T2 were 716 msec and 68 msec, respectively. Chemical shift artifacts were seen on MR images and were exaggerated when a narrow sampling bandwidth was used. In clinical cases spectral saturation pulses normally used for lipid suppression could be adjusted to saturate only the silicone resonance; in this way, the chemical shift artifact was eliminated. CONCLUSION: Intraocular silicone oil has unique imaging characteristics with which radiologists must become familiar. These characteristics include high attenuation on CT and hyperintensity on T1-weighted MR, both of which may mimic hemorrhage. Elimination of the prominent chemical shift artifact on MR with selective saturation of the silicone resonance improves evaluation of the globe. PMID- 8192084 TI - Steady-state free precession imaging of the inner ear. AB - The authors describe a steady-state free precession technique for imaging the inner ear. Although the signal-to-noise ratio is not as great as with other three dimensional MR techniques, the inherent high contrast of inner ear structures makes this a valuable technique for patients with sensorineural hearing loss and for those who refuse paramagnetic contrast material. PMID- 8192085 TI - Blinded comparison of cranial CT and MR in closed head injury evaluation. AB - PURPOSE: To compare CT and MR in the evaluation of acute head injury. METHODS: One hundred seven consecutive patients who were referred to the emergency department and underwent both MR and CT cranial examinations within 48 hours were retrospectively reviewed. The films were interpreted by two neuroradiologists blinded to all patient information. RESULTS: The sensitivity of MR was significantly higher than that of CT for the detection of contusion, shearing injury, subdural and epidural hematoma, and sinus involvement. The sensitivity of CT was significantly higher than that of MR for the evaluation of fracture. The sensitivities of MR and CT were statistically equivalent for the detection of superficial soft-tissue injury. The overall sensitivity of MR for the detection of abnormalities in acute head trauma was 96.4%, and for CT was 63.4%. CONCLUSIONS: CT and MR are complementary studies in the evaluation of acute head trauma. MR is necessary to define or exclude contusions, deep shearing injury, and extraaxial fluid collections in acute head trauma. PMID- 8192086 TI - Irradiated paragangliomas of the head and neck: CT and MR appearance. AB - PURPOSE: To present the spectrum of CT and MR findings of glomus tumors of the head and neck successfully treated with radiation therapy. METHODS: The patient charts and all CT and MR studies of 24 patients (25 tumors) who had been successfully treated with radiation therapy were retrospectively reviewed. Eighteen patients had pre- and posttreatment imaging studies. Tumor size, internal morphology, enhancement pattern, visualization of flow voids, and bone erosion were evaluated before and after radiation therapy. Statistical evaluation of the presence of flows voids and tumor size was performed using the Fischer Exact Test. RESULTS: All patients had residual tumor after radiation therapy. Sixty-one percent of tumors demonstrated a reduction in size. Only one tumor with pretreatment bone destruction demonstrated healing of the bone. MR findings after radiation therapy included variable alteration in T2 signal, decreased heterogeneous enhancement, and a reduction in flow voids. There was a significant difference in the presence of flow voids based on tumor size. CONCLUSIONS: Successfully irradiated paragangliomas demonstrate residual masses, the presence of which does not by itself indicate treatment failure. Stabilization or reduction in size, decreased enhancement, diminished flow voids, and reduced T2 signal after radiation therapy are a result of therapy and are indicative of local control. Persistent bone demineralization and erosion without progression is commonly seen in successfully controlled tumors. Paragangliomas are relatively homogeneous in internal morphology except for areas of flow void. Flow voids are not a reliable criterion for diagnosis in lesions less than 2.5 cm. PMID- 8192087 TI - A technique of measuring the precision of an MR-guided stereotaxic installation using anatomic specimens. AB - PURPOSE: To develop a method for direct measurement, using anatomic specimens, of the precision of MR-guided stereotaxic location and to describe its application to a 1.5-T MR unit with a Leksell stereotaxic frame. METHODS: Small pieces of gelfoam (1 X 1 X 1 mm), soaked in gadopentetate dimeglumine, were stereotaxically introduced into formalin-fixed human heads using a Leksell D (three experiments) or G (nine experiments) stereotaxic frame. The head and the frame were then introduced into a 1.5-T MR unit. The target coordinates (as set on the stereotaxic frame by one investigator) were then compared with the MR-determined stereotaxic coordinates (calculated independently by another investigator). The imprecisions Ex, Ey, and Ez in each direction were defined as the differences between the calculated and the chosen coordinates. RESULTS: Regarding the three targets studied with the D frame, mean imprecision Ex was 1.08 +/- 0.50 mm (mean +/- SEM), Ey 0.83 +/- 0.58 mm, and Ez 0.75 +/- 0.25 mm. For the nine targets studied with the G frame, Ex was 0.48 +/- 0.17 mm, Ey 0.69 +/- 0.14 mm, and Ez 0.82 +/- 0.13 mm. Statistical analysis of the results showed no significant difference between Ex or Ey and half the size of a pixel, indicating that, in the axial plane, stereotaxic MR precision is limited only by pixel size. A statistically significant difference was observed in the coronal plane between Ez and half the size of a pixel, but it must be stressed that Ez remained smaller than 1 mm. CONCLUSION: MR-guided stereotaxic location can be used with confidence for most diagnostic, functional, and therapeutic procedures. PMID- 8192088 TI - Proton MR spectroscopy in patients with seizure disorders. AB - PURPOSE: To evaluate the ability of proton MR spectroscopy to detect metabolic abnormalities in the seizure focus of humans with epilepsy. METHODS: Single-voxel MR spectroscopy and MR imaging was performed in a group of 13 patients with a variety of seizure disorders and in the temporal lobes of 14 healthy volunteers. Signals from choline, creatine, N-acetyl-L-aspartate, and lactate were quantitated in both the epileptogenic focus and the contralateral brain region. RESULTS: In normal temporal lobe, concentrations of choline, creatine, and N acetyl-L-aspartate were 2.0 +/- 0.7, 7.8 +/- 1.9, and 11.0 +/- 2.1 mumol/g wet weight, respectively, with no detectable lactate. In all patients, a reduction in the N-acetyl-L-aspartate signal was observed in the electrically defined (scalp electroencephalogram) seizure focus compared with the mirror-image contralateral side. Lactate was elevated only in patients who had seizures during or immediately before the MR examination. Seven of 13 patients studied had normal MR examinations. CONCLUSIONS: Proton spectroscopy demonstrates alterations in N acetyl-L-aspartate and lactate levels that can be used to locate the epileptogenic focus and may be a useful adjunctive diagnostic technique for the evaluation of patients with seizures who are eligible for resective surgery. PMID- 8192089 TI - An unruptured arteriovenous malformation with edema. AB - We report a case of unruptured arteriovenous malformation in which an extensive zone of increased signal intensity in the brain parenchyma adjacent to the nidus is demonstrated on T2-weighted MR. This area of perilesional hyperintense signal exerts a compressive effect, suggesting that it represents perilesional edema. PMID- 8192090 TI - Sturge-Weber syndrome with posterior fossa involvement. PMID- 8192091 TI - Posttraumatic cutaneous meningioma of the face. AB - We present the CT and MR features of a posttraumatic cutaneous meningioma of the face. We postulate that the patient's trauma and associated skull fracture resulted in a trapping of extracranial meningeal tissue, which many years later gave rise to a secondary facial meningioma. PMID- 8192092 TI - Annotated bibliography. PMID- 8192093 TI - Testing for drug abuse. PMID- 8192094 TI - Biotech products pose distribution challenges. PMID- 8192095 TI - Minimizing look-alike generic mix-ups. PMID- 8192096 TI - New drugs of 1993. PMID- 8192097 TI - Pharmaceutical care made easy. PMID- 8192098 TI - Oral iron supplements. PMID- 8192099 TI - Caring for contact lenses. PMID- 8192100 TI - Perspectives on pharmacy abroad. PMID- 8192101 TI - The role of prognostic factors in treatment selection for early-stage Hodgkin's disease. AB - PURPOSE: To identify poor prognostic factors in early-stage Hodgkin's disease that predict a high rate of relapse after radiotherapy alone. MATERIALS AND METHODS: A total of 153 patients with stages I and II supradiaphragmatic Hodgkin's disease, treated between 1964 and 1986 with either radiotherapy alone (120 patients) or combined modality therapy (33 patients), were studied retrospectively to determine factors affecting freedom from relapse and absolute survival. Median follow-up was 13 years. Clinical factors were assessed by the stepwise use of a stratified log-rank test and included maximum tumor dimension in any site (< or = 6 cm or > 6 cm), age (< or = 40 or > 40), presence or absence of B symptoms, pathologic and clinical stages (I or II), number of sites involved (< or = 4 or > 4), gender, histologic subtype, and large mediastinal mass (none, small [< or = 6 cm], large [> 6 cm]). RESULTS: The only factors independently predicting a high rate of relapse were tumor dimension (> 6 cm) and number of sites (> 4 sites). At 10 years, in patients with and without the two poor prognostic factors treated with radiotherapy alone, the freedom from relapse rates were 53% and 84% (p < .0001) and the absolute survival rates were 72% and 85% (p = .004), respectively. Combined modality therapy significantly improved freedom from relapse, but not absolute survival, in patients with one or both poor prognostic factors. CONCLUSIONS: Two poor prognostic factors were identified that were highly significant in predicting a high risk of relapse after radiotherapy alone. The addition of three cycles of chemotherapy to standard radiotherapy significantly reduced the relapse rate in high-risk patients. PMID- 8192102 TI - Carboplatin in previously treated multiple myeloma. A Cancer and Leukemia Group B phase II trial. AB - Carboplatin 400 mg/m2 per month was evaluated as a single agent in 15 patients with multiple myeloma who had had one prior chemotherapy regimen. All but three were judged to have had some degree of refractoriness to prior therapy. Hematologic toxicity was frequent and sometimes severe. There were no responses. Further evaluation of standard-dose single-agent carboplatin in refractory myeloma does not appear warranted. PMID- 8192103 TI - Double 5-fluorouracil modulation with folinic acid and recombinant alpha-2B interferon. A phase I-II study in metastatic colorectal cancer patients. AB - Twenty-two patients with metastatic colorectal cancer entered a Phase I-II trial to assess the maximum tolerable dose of alpha-2B-interferon administered intramuscularly three times per week in combination with fixed doses of 5 fluorouracil (450 mg/m2 IV for 5 days, and, from day 28, weekly) and folinic acid (200 mg/m2 IV before 5-fluorouracil) and the efficacy of this combination. Diarrhea and mucositis were the most frequent 5-fluorouracil-related toxicities and were > or = ECOG grade 3 in 23% and 18% of patients, respectively. Of 15 patients receiving interferon > or = 9 x 10(6) IU, 10 required interferon dose reduction mostly because of severe fatigue, anorexia, and declining performance status. Among 19 patients evaluable for response, 3 achieved a partial response and 1 a complete response for an overall response rate of 21% (95% confidence interval, 6-46%). In conclusion, our study demonstrates that IFN-alpha 2B at doses higher than 6 x 10(6) IU intramuscularly three times per week in the combination with 5-fluorouracil and folinic acid we used is too toxic for the majority of patients; this combination has moderate activity in metastatic colorectal cancer, although similar response rates have been reported, with less toxicity, with 5-fluorouracil plus folinic acid without IFN-alpha. A larger Phase III study would be required to determine the value of IFN-alpha in this combination. PMID- 8192104 TI - Phase II trial of acivicin versus etoposide-cisplatin in non-small cell lung cancer. An Eastern Cooperative Oncology Group study. AB - Identification of effective new chemotherapeutic agents is a major objective of clinical research efforts in patients who have metastatic non-small cell lung cancer (NSCLC). Canadian investigators observed responses in NSCLC when acivicin was given as a daily IV bolus for 5 consecutive days. Based on these results the Eastern Cooperative Oncology Group tested acivicin as a continuous infusion in patients with advanced NSCLC. A total of 82 patients were entered on a Phase II trial in which patients have randomized either to acivicin 60 mg/m2 given as a continuous intravenous infusion over 72 hours repeated every 28 days or to the reference regimen which consisted of cisplatin 60 mg/m2 intravenously on day 1 and etoposide 120 mg/m2 daily on days 1, 2, and 3 repeated every 28 days. Five partial remissions (11%) were observed in 42 patients treated with etoposide cisplatin, and no responses were observed in 40 patients treated with acivicin. Median survival durations for etoposide cisplatin and for acivicin were 29.7 and 21.1 weeks, respectively. Based on these results, acivicin appears to be inactive in NSCLC. PMID- 8192105 TI - Mitomycin C and mitoxantrone in anthracycline-pretreated advanced breast cancer patients. A phase II study. AB - Twenty-one patients with anthracycline-pretreated advanced breast cancer were treated with mitomycin C plus mitoxantrone (MM), 10 mg/m2, on day 1 of a 28-day cycle. All patients were evaluated for toxicity and response. Overall, 83 cycles were administered, with a median number of 4 cycles per patient. Hematologic toxicity, not requiring hospitalization, was the major side effect. Vomiting occurred in 19.2% of cycles. Objective response rate was 33.3% (95% confidence interval: 12.2-53.1%); best responses were 1 complete and 6 partial; also 7 stable and 7 progressive disease were recorded. The best responding site was the viscera, the worst was bone. Responses were seen preferentially in second- rather than in third-line therapy and in patients who had responded to previous chemotherapy, although differences were not statistically significant. Kaplan Meier estimated median time to progression and overall survival were 26 weeks (range: 2-67 weeks) and 35 weeks (range: 6-79 weeks), respectively. In conclusion the MM regimen showed acceptable toxicity and appreciable activity in anthracycline-pretreated advanced breast cancer. PMID- 8192106 TI - Epirubicin-sequential methotrexate-5-fluorouracil-leucovorin treatment in advanced cancer of the extrahepatic biliary system. A phase II study. AB - A combination chemotherapy was used to treat patients with advanced cancer of the extrahepatic biliary system not amenable to surgical resection. Between February 1985 and April 1992, 22 consecutive patients entered into the study; 17 (11 with extrahepatic bile duct cancer and 6 with gallbladder cancer) were evaluable for response and toxicity. The treatment schedule was as follows: epirubicin 20 mg/m2 given as a bolus, followed by methotrexate 150 mg/m2 as a 30-minute infusion, 1 hour later 5-fluorouracil 600 mg/m2 as a 30-minute infusion. Leucovorin rescue (15 mg orally every 6 hours for eight doses) was started 24 hours after methotrexate. This course was administered once a week in 3 successive weeks followed by a 2 to 3 weeks rest period. A total of 174 courses was given. No objective tumor regression was observed. This regimen was well tolerated, the main toxicity being gastrointestinal. The median survival time for the 17 evaluable patients was 9 months. PMID- 8192107 TI - Colon carcinoma metastatic to the trachea. Report of a case and a review of the literature. AB - Tracheal metastases are rarely seen from colorectal carcinoma. We describe the third reported case of colorectal carcinoma metastatic to the trachea and review of the current pathogenesis, diagnosis, and management of endotracheal metastases. PMID- 8192108 TI - Retroperitoneal lymphadenectomy, including the para-aortic nodes in patients with stage III ovarian cancer. AB - The role of lymphadenectomy in patients with advanced ovarian cancer is controversial. To evaluate the effect of lymphadenectomy, we retrospectively assessed the outcome of 53 patients with stage III epithelial ovarian cancer who were divided into two groups, which were matched for age distribution and postoperative chemotherapy, but received different surgical procedures. A total of 29 patients (group A) underwent hysterectomy, bilateral salpingoophorectomy, omentectomy, and retroperitoneal lymphadenectomy, including resection of the para aortic nodes. The remaining 24 patients (group B) received hysterectomy, bilateral salpingoophorectomy, and omentectomy without retroperitoneal lymphadenectomy. Postoperative chemotherapy consisted of a combination of cisplatin, Adriamycin, and cyclophosphamide in both groups. The 2-year survival rate for group A was significantly greater than that for group B, but there was no significant difference between the groups with regard to the estimated 5-year survival rate. The 2-year survival rate of patients with positive nodes who underwent lymphadenectomy was similar to that of patients with negative nodes. Multivariate analysis indicated that lymph node involvement did not relate to prognosis of the patients undergoing lymphadenectomy. While a defined randomized trial is required to reach substantive conclusion, it is suggested that lymphadenectomy may be useful for improvement of the prognosis of patients with advanced ovarian cancer. PMID- 8192109 TI - The role of steroids in the management of metastatic carcinoma to the brain. A pilot prospective trial. AB - This prospective study attempted to evaluate the indications for glucocorticoids which are commonly given to patients with brain metastases. Twelve patients with histologically confirmed malignancies and radiographically documented brain metastases were enrolled. Patients were scored for general performance status and neurologic function class. All subjects were given high-dose dexamethasone (HDD) for 48 hours and then randomized to receive either intermediate-dose dexamethasone (IDD) or no steroids with cranial radiotherapy. Of these 12 study patients, 3 achieved a complete response, 1 partial response, and 8 nonresponses to HDD. Seven patients had IDD, while five received no IDD. Although a small sample size prevented any statistical analysis, this study does suggest that the place for using glucocorticoids in treating patients with metastatic carcinoma to the brain remains uncertain and should be evaluated in a cooperative prospective trial. PMID- 8192110 TI - Cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil for the treatment of metastatic non-small cell lung cancer. Limited activity of an aggressive chemotherapy regimen. AB - We conducted a Phase II study to determine the efficacy of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil in patients with untreated non-small cell lung cancer. Patients were accrued through the Connecticut Oncology Association (COA), an organization composed of community and university oncologists. Thirteen COA oncologists enrolled 30 patients over 12 months and 26 were eligible for the final analysis. Patients received cisplatin 75 mg/m2, doxorubicin 30 mg/m2, mitomycin C 6.5 mg/m2, and 5-fluorouracil 750 mg/m2 on day 1. The treatment was repeated every 4 weeks, with mitomycin C given during the first 3 cycles and then every other cycle. There were 5 (19%) partial responses, lasting 1.3-7.3 months. The median time to progression was 10.3 months (0.3-12.5 months). Median survival was 7.5 months (0.3-34 months). The major toxicities were related to myelosuppression and there was one septic death. This study demonstrates the limited efficacy of an aggressive regimen using "active" agents in patients with advanced non-small cell lung cancer. PMID- 8192111 TI - Phase I study of retelliptine dihydrochloride (SR 95325 B) using a single two hour intravenous infusion schedule. AB - Retelliptine dihydrochloride (SR 95325 B, NSC D-626717-W) is an ellipticine derivative having a very high level of antitumor activity in resistant murine solid tumor models. We studied in a Phase I trial escalating doses of retelliptine using a single 2-hour IV infusion schedule. Data from other Phase I studies allowed a starting dose of 80 mg/m2 and a rapid dose escalation. Included were 15 patients (M/F = 13/2) with a median age of 55 (range: 17-72). There were 22 courses delivered at the following dose levels: 80, 180, 700, 900, 1,200, and 1,500 mg/m2. Primary tumor types were kidney (6 patients), colon (3 patients), pancreas (2 patients), and others (4 patients). Mild dose-related visual troubles (blurring, accommodation troubles, oculomotor paresis) occurred in 9/11 patients starting from 700 mg/m2. Asymptomatic EKG anomalies, including significant prolongation of PR and QRS intervals occurred at 1500 mg/m2 (in 3/3 patients) marking the maximum tolerated dose. Both visual and EKG anomalies were spontaneously reversible few minutes to few hours after the end of infusion. Other possible drug-related toxicity occurred sporadically such as somnolence, bronchospasm, dry mouth, and vomiting (2 patients each). There were no significant laboratory anomalies. Neither drug-related deaths nor objective complete or partial responses were observed. The recommended dose for Phase II trial using the 2-hour intravenous infusion schedule is 1,200 mg/m2. PMID- 8192112 TI - Allopurinol mouthwashes in the treatment of 5-fluorouracil-induced stomatitis. AB - This study was aimed at assessing the efficacy of allopurinol mouthwashes in the treatment of 5-fluorouracil-induced stomatitis. A randomized double-blind, placebo-controlled trial was thus designed to test its efficacy to treat oral mucositis in advanced cancer patients receiving 5-fluorouracil-containing chemotherapy. There were 44 patients randomized to receive allopurinol mouthwashes, or placebo, as soon as mucosal lesions were observed during any treatment cycle. Stomatitis was evaluated at the end of each 5-day treatment cycle. Allopurinol mouthwashes resolved stomatitis in 9 of 22 treated patients (40.9%), and diminished its intensity in 10 more patients (45.4%); stomatitis resolved completely in none of the 22 patients, and partially in 3 patients in the placebo group (p < .001 by chi 2 test). Duration of symptoms was also significantly different between the two groups (median: 4 days for the allopurinol group, 7.5 days for the control group; p < .0005 by Student's t test). In conclusion, our results suggest that allopurinol mouthwashes can be effective to treat 5-fluorouracil-induced stomatitis. PMID- 8192113 TI - Radiation osteitis and insufficiency fractures after pelvic irradiation for gynecologic malignancies. AB - Damage to the pelvic bones after radiotherapy for gynecological malignancies is uncommon with megavoltage radiotherapy. It can be misdiagnosed as bony metastases and is a diagnosis of exclusion. We report 12 women, who were treated for endometrial or cervical carcinoma who developed osteitis, femoral head or neck necrosis, or insufficiency fractures of the acetabulum, pubic symphysis or sacroiliac bones after radiotherapy. Many had multiple areas of bone damage. The prescribed external beam dose ranged from 40.0 to 61.2 Gy. All but one patient developed bony discomfort or pain as a symptom. Bony changes of the pelvic girdle appeared between 6 months and 8 years after irradiation. Radiographic studies including plain films, CT or bone scans were performed in these patients and showed correlative changes. Bone scans showed increased radionuclide uptake in affected bones. The subsequent favorable clinical course and outcome with resolution of symptoms confirmed the diagnosis of radiation osteitis. Therapy recommendations are conservative with avoidance of weight-bearing, use of analgesics and physical therapy. Femoral head necrosis/fractures required arthroplasty. Proper shielding, use of multifield technique, treatment of all fields per day, and awareness of tolerance doses are recommended. PMID- 8192114 TI - Extracorporeal photopheresis and recombinant interferon alfa 2b in Sezary syndrome. Use of dual marker labeling to monitor therapeutic response. AB - The purpose of this pilot study was to evaluate the role of recombinant interferon alfa 2b (rIFN-a) as adjunct immunomodulatory therapy in patients with Sezary syndrome who were considered unlikely to respond to ExP alone. Six patients were treated with rIFN-a in doses ranging from 3 to 20 million units three times weekly in addition to two consecutive photopheresis treatments every 4 weeks. In addition, to better measure the effect of treatment on circulating neoplastic T-cells, cryopreserved lymphocytes were studied by two-color immunofluorescence and flow cytometry, using anti-CD4 combined with anti-CD29, anti-CD45RA, or anti-CD7. Minimal clinical improvement was observed in 4 patients treated with low doses of rIFN-a (3 to 5 million units TIW), and the response was sustained in only 1 patient. However, a clinically significant and sustained improvement did occur in 1 patient after the dose of rIFN-a was increased (20 million units TIW). Although the encountered toxicity profile from combined ExP/rIFN-a therapy was similar to that expected for ExP or comparable doses of rIFN-a given separately, treatment was discontinued in 2 patients because of adverse effects. Three antibody pairs, i.e., CD4+CD7-, CD4+CD29+, and CD4+CD45RA- subsets, appeared to be useful to monitor changes in blood Sezary cells during treatment. We conclude that the combination of ExP and low doses of rIFN-a does not appear to be effective for patients with advanced Sezary syndrome in this small patient series. However, escalation of interferon dose may be beneficial as shown in one patient, but it cannot be discerned whether the response was due to a combination of therapies, or whether the same therapeutic response would have been achieved with the higher doses of rIFN-a alone. Moreover, while none of the antibody pairs is unique for Sezary cells, the CD4+CD7- subset in appropriate patients provided a good objective measure of response and correlated well with visual Sezary cell counts. PMID- 8192115 TI - Long-term results of "selective sandwich" adjunctive radiotherapy for cancer of the rectum. AB - A total of 132 patients with adenocarcinoma of the rectum were treated in a program of "selective sandwich" adjunctive radiation therapy and have been followed for a minimum period of 5 years. All patients were given a single dose of preoperative radiation, 500 cGy, either on the day of or the day before surgery. At surgery, 12 patients with metastatic disease were treated palliatively. The remaining 120 patients underwent radical curative surgery. Patients were then staged histopathologically according to the Astler-Coller modification of Dukes' staging: 34 patients with stage A or B1 disease were followed with no further treatment; 54 patients with stage B2 or C cancer received a planned course of high-dose postoperative radiation (4,500 cGy in 5 weeks); 32 patients with stage B2 and C cancer received no further treatment. Radiation therapy was well tolerated with few long-term side effects. None of the patients receiving low-dose preoperative radiation alone had any complications. Two patients (4%) treated with the combined pre- and postoperative radiation experienced major small bowel complications. Local recurrence was observed in 11 of 32 patients (34%) with stage B2 and C disease receiving low-dose preoperative radiation alone, as compared to 5 of 54 patients (9%) of the combined pre- and postoperative radiation group. The absolute 5-year survival in these two groups is 54% and 72%, respectively. With follow-up now exceeding 5 years, the survival of patients treated with the planned approach of combined pre- and postoperative radiation continues to remain appreciably better than for patients receiving low dose preoperative radiation alone. PMID- 8192116 TI - Randomized phase II trial comparing two versus three doses of ondansetron when used in combination with dexamethasone in patients receiving cisplatin > or = 100 mg/m2. AB - Ondansetron controls cisplatin-induced emesis when given in three 0.15 mg/kg doses, and preliminary data suggest that control may be maintained when fewer doses are employed. Prior trials have further shown improved antiemetic effects and fewer adverse effects of cisplatin treatment when neurotransmitter receptor blockers are combined with dexamethasone. This trial was undertaken to determine the effectiveness of the combination of dexamethasone and ondansetron and to see if equivalent results could be obtained with only two doses of ondansetron. There were 44 patients receiving initial cisplatin at a dose > or = 100 mg/m2, each given dexamethasone 20 mg and randomized to receive either two or three 0.15 mg/kg doses of ondansetron. Vomiting prevention was identical (35%) whether two or three doses were given. No new adverse effects were noted and cisplatin induced diarrhea, usually seen in up to 60% of patients given this dose of cisplatin, was noted in only 5%. Although this trial did not demonstrate enhanced antiemetic effects with the combination, other investigators have done so and all agree that the regimen is safe and reduces adverse effects. Further exploration and use of the combination of ondansetron and dexamethasone, and studies testing fewer doses of ondansetron in this regimen are warranted. PMID- 8192117 TI - Clinicopathologic correlations and short-term prognosis in musculoskeletal sarcoma with c-myc oncogene amplification. AB - The prognostic significance of c-myc oncogene amplification was investigated in a series of 44 patients with musculoskeletal malignancy. There were 21 bone tumors and 23 soft tissue sarcomas. Amplification of the c-myc oncogene was detected in 11 tumors: 4 bone tumors and 7 soft tissue sarcomas. In 9 of the 11 myc-amplified tumors a high grade of malignancy was revealed histologically. The relative frequency of c-myc amplification was higher in grade IV tumors. After a mean follow-up of 18 months, 6 of 11 patients with c-myc-amplified tumors and 12 of 33 patients with nonamplified tumors either exhibited recurrence or died of tumor disease. Both 3-year estimated overall survival and disease-free survival probability were lower for patients with myc-amplified tumors. Amplification of the c-myc oncogene was associated with poor short-term prognosis. Although gene amplification was encountered sporadically in musculoskeletal sarcomas, the reported data suggest that analysis of c-myc may provide valid information on prognosis. PMID- 8192118 TI - The contexts of adolescents' chronic life stressors. AB - Proposed and tested a model of the determinants of adolescents' chronic life stressors, consisting of sociodemographic, personal, and contextual stress and coping factors, using baseline and 1-year follow-up data from 259 adolescents who varied in their psychological and physical health. Concurrent regression analyses at Time 1 and at Time 2, and longitudinal regressions that controlled for the levels of chronic stressors 1 year earlier, showed that sociodemographic, personal, and contextual factors each made a significant contribution to predicting adolescents' ongoing stressors with their mother, father, siblings friends and classmates and teachers at school. Personal factors of an emotional temperament and low perceived self-worth, and contextual factors of more negative life events and fewer social resources, were related to more chronic stressors. Suggestions for further development of the model are discussed. PMID- 8192119 TI - Lesbian, gay, and bisexual youth in community settings: personal challenges and mental health problems. AB - Studied 194 lesbian, gay, and bisexual youth aged 21 and younger who attended programs in 14 community centers to determine the personal challenges they face due to their sexual orientation and their responses to these stresses. First awareness of sexual orientation typically occurred at age 10, but disclosure to another person did not occur until about age 16. There was much variability in sexual behavior, and many youths reported both same-sex and opposite-sex sexual experiences. Although most had told at least one family member about their sexual orientation, there remained much concern about family reactions. Suicide attempts were acknowledged by 42% of the sample. Attempters significantly differed from nonattempters on several milestones of sexual orientation development, social aspects of sexual orientation, parents' knowledge of sexual orientation, and mental health problems. PMID- 8192120 TI - The social context of Hong Kong's booming elderly home industry. AB - Hong Kong experienced a rapid increase in private homes for elderly people in recent years. This paper examines the social background of that development. Private elderly homes thrived in a context of rising demand due to changing demographics, particularly massive emigration secondary to political instability, which created a large potential market of elderly people in need of residential care. However, entrepreneurs would not be attracted unless it is a profitable business, and much of that profit is likely derived from social security payments to elderly people. Because the amount of social security benefits is way below the level required for purchasing good quality service in the private sector, many elderly people are bound to ive in very poor residential settings. PMID- 8192121 TI - Early education as community intervention: assisting an ethnic minority to be ready for school. AB - An early education program designed for an ethnic minority of Native Hawaiians implemented at the community rather than the individual child level of intervention is described. The program development effort is theory driven and provides an opportunity to investigate the application of neo-Vygotskian theory to an applied community educational problem. Though not specifically derived from the work of O'Donnell, Tharp, and Wilson (1993), the project reported here shares a common intellectual heritage. This paper demonstrates the parallels between the early education program developed for Hawaiian children and the applicability of the theory presented in the work of O'Donnell et al. PMID- 8192122 TI - The social construction and subjective reality of activity settings: implications for community psychology. AB - A major focus of the article is the idea that activity settings are in part social constructions of the participants. The socially constructed "meaning" of an activity setting is a complex mix of ecological, cultural, interactional, and psychological features. These features may be observed and assessed, directly and indirectly, in terms of personnel, cultural values, tasks, scripts for conduct, and motives and purposes of actors. Empirical illustrations and extensions to community psychology are drawn from research with different populations: Native Hawaiian children and families, Spanish-speaking children and Mexican and Central American immigrant parents, Euro-American families with a developmentally delayed child, and Euro-American families who intentionally adopted nonconventional child rearing values and practices. PMID- 8192123 TI - Probing the effects of individual components in multiple component prevention programs. AB - Assessing the contributions of individual components in multi-component interventions poses complex challenges for prevention researchers. We review the strengths and weaknesses of designs and analyses that may be useful in answering three questions: (1) Is each of the individual components contributing to the outcome? (2) Is the program optimal? and (3), Through what processes are the components of the program achieving their effects? Factorial and fractional factorial designs in which a systematically selected portion of all possible treatment combinations is implemented are used to address question 1. Response surface designs in which each component is quantitatively scaled are explored in relation to question 2. Mediational analysis, a hybrid of experimental and correlational approaches, is considered in relation to question 3. Design enhancements are offered that may further strengthen some of these techniques. These techniques offer promise of enhancing both the basic science and applied science contributions of prevention research. PMID- 8192124 TI - Primary prevention of secondary disorders: a proposal and agenda. AB - This paper calls for consideration of a new class of preventive interventions designed explicitly to prevent comorbidity of psychiatric disorders. Epidemiologic data show that successful interventions of this type could be extremely valuable, as up to half of lifetime psychiatric disorders and an even larger percent of chronic and seriously impairing disorders occur to people with a prior history of some other disorder. Furthermore, a review of etiologic hypotheses concerning the causes of comorbidity suggests that interventions aimed at primary prevention of secondary disorders might be feasible. However, more basic risk factor research is needed on the causes of comorbidity before we can make a clear assessment of feasibility and discover promising intervention targets. A number of methodological problems arise in carrying out this type of formative research. These problems are reviewed and suggestions are offered for solutions involving innovations in measurement, design, and data analysis. PMID- 8192125 TI - Analyzing preventive trials with generalized additive models. AB - Described a new class of nonparametric regression procedures called generalized additive models (Hastie and Tibshirani, 1991) for assessing intervention effects in mental health preventive field trials. Such models are often better than analysis of covariance models for examining intervention effects adjusted for one or more baseline characteristics and for assessing potential interactions between the intervention and baseline characteristics. Because of these advantages, generalized additive models are important tools analysts should consider in evaluating preventive field trials. We apply generalized additive models as well as more standard linear models to data from a preventive trial aimed at improving mental health and school performance outcomes through a universal intervention in first and second grades. Practical guidance is given to researchers regarding when generalized additive models would be beneficial. PMID- 8192126 TI - Preventing problems in prevention research. AB - The design, conduct, and analysis of prevention research efforts present formidable challenges, but as the papers in this volume illustrate, the problems of prevention research are probably not altogether intractable; they simply require the best of our thinking and the firmest of our commitments. The papers included in this issue represent some of the best thinking likely to be available, and, in aggregate, they give reason for some optimism about prevention research. Which is fortunate, because it is by now abundantly clear that treatment of all the assorted personal and social maladies that afflict us individually and as a society, is impossibly intrusive and expensive, even if we were certain we knew what to do, and we are not. Treatment research is only a step or two ahead of prevention research in nearly any field. PMID- 8192127 TI - Counting the stitches that count: preventive intervention promises and public health. AB - Continued public support for the design, implementation, and dissemination of preventive interventions depends on achievement of four major criteria: (a) Reductions in the incidence or prevalence rates of diagnosable emotional and behavioral disorders, (b) reductions in the need for mental health services through effective primary and secondary interventions, (c) enhancement of the effectiveness of obtained services as screening and early detection efforts are implemented, and (d) reductions in the nation's health care costs associated with emotional and behavioral dysfunctions. Strategies including risk reduction, risk avoidance, health promotion, empowerment, and resource development are preventive insofar as they contribute to achievement of the aforementioned outcomes. PMID- 8192128 TI - Outpatient treatment for cocaine abuse: a controlled comparison of relapse prevention and twelve-step approaches. AB - This study sought to assess the efficacy of treatment for cocaine abuse and to compare the relative effectiveness of a cognitive-behavioral relapse prevention treatment with that of a Twelve-Step recovery support group in an outpatient group treatment setting. One hundred ten subjects seeking treatment were alternately assigned to relapse prevention or Twelve-Step treatment. Self-report data were collected at baseline, posttreatment, and 6-month follow-up. There were no differential effects of treatment type on cocaine or marijuana use over time. However, subjects in both treatment conditions reduced cocaine and marijuana use at posttreatment. Subjects in both groups reduced their alcohol use from pretreatment to posttreatment. Subjects receiving Twelve-Step treatment showed greater increases from posttreatment to 6-month follow-up in alcohol use than did relapse prevention participants. Treatment attendance was negatively related to cocaine use at posttreatment and cocaine and marijuana use at 6-month follow-up. Difficulties in conducting cocaine treatment outcome research are discussed as are treatment and research implications of the findings. PMID- 8192129 TI - HIV-1 among inner city dually diagnosed inpatients. AB - The objectives of this study were to investigate HIV-1 seroprevalence and risk factors, disease progression, and awareness of HIV-1 serostatus in a population of inner city, substance using, psychiatric inpatients. To pursue these goals, we tested 118 (103 M, 15 F) dually diagnosed, acute care inpatients for HIV-1 antibodies and administered structured interviews. Twenty-seven (23%, including 24 M and 3 F) of the subjects were HIV-1 seropositive. Seropositivity was twice as great among intravenous drug users and men who had sex with other men as among patients not belonging to either of these two groups. Logistic regression analysis among male subjects revealed a significantly elevated HIV-1 risk associated with a primary diagnosis of depression (odds ratio adjusted for age, race, and presence of an AIDS risk behavior = 4.2, 95% confidence interval = 1.1, 16.5; p = 0.04). Less than half of the seropositives knew their HIV-1 status prior to this study, one had AIDS and four had two or more constitutional symptoms of AIDS. The high rate of seropositivity in this indigent, dually diagnosed population presents challenges to the health-care community. That few individuals had HIV-1 related symptoms may have implications for other treatment settings. PMID- 8192130 TI - Propranolol versus diazepam in the management of the alcohol withdrawal syndrome: double-blind controlled trial. AB - Thirty-seven male alcoholics admitted electively for detoxification were randomized to treatment with either diazepam or propranolol. Subjects were comparable both in age and in duration and quantity of alcohol consumed. Admission laboratory parameters did not distinguish between the groups. Eleven subjects required no medication to control withdrawal signs/symptoms. Both groups showed improvement in blood pressure, pulse, and withdrawal tremor. None of the subjects randomized to diazepam manifested withdrawal seizures or hallucinations. By contrast, one subject in the propranolol group had a single withdrawal seizure. Another subject manifested increasing withdrawal that required parenteral paraldehyde treatment. Thus, this study confirms that a significant number of subjects admitted electively for alcohol withdrawal can be managed without medication. Minor tranquilizers still remain the "gold standard" for management of the withdrawal syndrome. PMID- 8192131 TI - Abuse of monoamine oxidase inhibitors. PMID- 8192132 TI - Discriminating between high and low volume substance abusers by means of the Drug Lifestyle Screening Interview. AB - One hundred and twenty inmates enrolled in a comprehensive residential drug treatment program were administered the Drug Lifestyle Screening Interview (DLSI), a structured interview designed to assess the four behavioral characteristics of lifestyle drug abuse: i.e., irresponsibility/pseudoresponsibility, stress-coping imbalance, interpersonal triviality, and social rule breaking/bending. Subjects reporting a high volume of prior substance misuse (moderate to severe abuse of at least three different substances or severe abuse of one substance other than marijuana) recorded significantly higher scores on each of the four behavioral dimensions of lifestyle drug abuse than subjects possessing a lower volume of prior substance misuse. Furthermore, a score of 10 or higher on the DLSI cumulative index classified 76.7% of the high volume users but only 37.2% of the low volume users as lifestyle drug abusers for an overall hit rate of 71.7%. PMID- 8192133 TI - Preemployment drug screening at the Johns Hopkins Hospital, 1989 and 1991. AB - During identical 2-month periods in 1989 and 1991, all applicants for employment at a major teaching hospital participated in preemployment drug screening. In 1989, before establishment of a formal preemployment testing program, screening was conducted without identifying information. Of 593 applicants screened, 64 (10.8%) were confirmed positive for one or more drugs. Marijuana metabolites were detected with the greatest frequency (35 samples, 55% of positive screens), followed by cocaine (36%), then opiates (28%). In 1991, after a formal preemployment testing program was in place, 365 applicants were screened, and 21 (5.8%) were confirmed positive. Opiates were most often detected (48% of positive screens), followed by cocaine (38%), then marijuana metabolites (28%). During both periods, positive urine screens were associated with ethnicity (non-White) and occupational category (blue-collar). Whereas in 1989 positive screens were associated with male gender, in 1991, females were more likely to test positive. The decline in prevalence following implementation of a screening program supports the notion that preemployment testing can serve as a deterrent for drug using persons in applying for employment. PMID- 8192134 TI - Participation of significant others in outpatient behavioral treatment predicts greater cocaine abstinence. AB - The present study was conducted to identify predictors of cocaine abstinence during outpatient behavioral treatment for cocaine dependence. Subjects were 52 cocaine-dependent adults. Stepwise logistic regression was used to identify predictors of abstinence during a 12-week treatment program. Demographic, drug use, and other subject characteristics were examined. The single best predictor of cocaine abstinence was whether a significant other participated in treatment. The odds of achieving a criterion level of cocaine abstinence were approximately 20 times greater for subjects who had a significant other participate in treatment. Importantly, significant others participated in a structured form of relationship counseling and behavioral contracting that is well specified and can be readily tested in a prospective, randomized trial. Considering the pressing need for the development of effective treatments for cocaine dependence, such a trial merits consideration. PMID- 8192135 TI - A quasi-experimental evaluation of Students Against Driving Drunk. AB - The current research was designed to assess the effectiveness of one nationally prominent and highly publicized driving while intoxicated (DWI) prevention program for youth, Students Against Driving Drunk (S.A.D.D.). Process and outcome data were collected over a 2-year period in two states--California and New Mexico. In each state, one treatment school which implemented S.A.D.D. was compared to a closely matched comparison school on a variety of DWI-related measures over three waves of survey data collection. Process data indicated that in neither school was the entire S.A.D.D. model implemented. Student participation was moderate in the California school and marginal in the New Mexico school. There was also little evidence that S.A.D.D. stimulated increased curriculum attention to DWI issues. Outcome data provided no evidence for effects of S.A.D.D. on any of the DWI measures. General maturational trends in these variables were observed in the study cohorts, but these trends were not differentiated between the treatment and comparison schools. There was also no support for the concern that S.A.D.D. may stimulate student drinking by encouraging alternative means of transportation for intoxicated students. PMID- 8192136 TI - A prediction model for identifying alcohol withdrawal seizures. AB - A retrospective review of alcohol withdrawal seizures was performed at a private chemical-dependence treatment facility to help identify patients who were at high risk for having a seizure. Patients were identified by two means: controlled substance records were reviewed to determine patients having received intramuscular phenobarbital, and patient charts were reviewed for all patients with a discharge diagnosis of a seizure disorder. Two thousand and one patient records were reviewed; alcohol withdrawal seizure patients were identified. Twenty-eight randomly selected nonseizure patient records served as controls. The statistical test consisted of a discriminant function analysis. The data yielded a statistically significant predictive model for alcohol withdrawal seizures based on six interdependent patient variables which will be helpful in treating future patients undergoing alcohol withdrawal. PMID- 8192137 TI - Retention of resistant subjects in longitudinal studies: description and procedures. AB - This paper discusses efforts to retain resistant subjects (N = 88) in a prospective research project which investigates the effects of prenatal substance use on pregnancy and infant outcome. Resistant subjects were women for whom we had valid addresses and/or phone numbers. They did not refuse to participate but were reluctant to schedule appointments and/or keep scheduled appointments. The persistent resistance we encountered led us to develop procedures which established and maintained rapport with resistant respondents and facilitated access to the 18-month assessment. No significant differences were found between the resistant participants and nonresistant subjects on six sociodemographic factors and on substance use. However, resistant subjects were significantly more depressed than nonresistant subjects. Anxiety and hostility did not differ at any time point. Resistant subjects who were finally interviewed, reported a significantly higher number of recent life events than nonresistant subjects at the 18-month postpartum interview. The follow-up rates for retaining the 88 resistant subjects were 44.3, 72.7, and 79.6% at Phases 4, 5. and 6, respectively. PMID- 8192138 TI - Prevalence of chronic diseases and impairments among US farmers, 1986-1990. AB - Farmers in the United States suffer disproportionately from certain chronic diseases and impairments. This analysis estimated the prevalence of selected diseases among farmers and compared these rates with those for other US workers. Five years (1986-1990) of National Health Interview Survey data on white male workers were combined to provide a basis for estimating the prevalence of selected conditions and impairments among this subgroup. Crude prevalence rates were significantly elevated for farmers compared with other workers for cardiovascular diseases, arthritis, skin cancer, hearing loss, and amputations. These elevations persisted when farmers were compared with blue-collar workers. The crude prevalence of orthopedic impairments and chronic respiratory diseases was not elevated among farmers, but the age-adjusted prevalence ratios for cardiovascular diseases, arthritis, and amputations were significantly elevated for farmers as compared with other workers. The prevalence of hearing loss was significantly higher only for farmers older than 65 years. This method of pooling data holds promise for studying disease rates in other small segments of the US population. PMID- 8192139 TI - Height, lung function, and mortality from cardiovascular disease among the elderly. AB - The relation between height and death from cardiovascular disease was studied in a cohort of 3,809 persons aged 65 years or older (85% of eligible individuals) enrolled in a population survey in 1982-1983 in East Boston, Massachusetts. Self reported height and weight were obtained, and peak expiratory flow rate (PEFR) was measured using a mini-Wright peak flow meter (Armstrong Industries, North Brook, Illinois). Vital status and cause of death were obtained through 1988. The median height was 62 inches in women and 66 inches in men. After adjustment for age, body mass index, and cigarette smoking, the risk of cardiovascular death decreased with quintile of height in women, with relative risks of 1.65, 1.16, 1.15, 0.76, and 1.00 over successive quintiles, with the tallest as the referent (p trend = 0.015). The trend in men was not as strong, with relative risks of 1.22, 0.77, 0.90, 0.98, and 1.00 from the shortest to the tallest quintiles (not significant). In both men and women, the strongest association was found with height and height squared, indicating a curvilinear relation. Height remained a predictor in women after adjustment for PEFR and other risk factors. These data suggest that a relation between height and cardiovascular death that is not mediated by lung function exists in the elderly, at least among women. PMID- 8192140 TI - Progression of human immunodeficiency virus type 1 (HIV-1) infection among homosexual men in hepatitis B vaccine trial cohorts in Amsterdam, New York City, and San Francisco, 1978-1991. AB - The authors evaluated the progression of human immunodeficiency virus type 1 (HIV 1) disease from the date of seroconversion to the development of acquired immunodeficiency syndrome (AIDS) and death among 362 well-documented seroconverters. The participants were homosexual men in hepatitis B vaccine trials in Amsterdam (n = 74), New York City (n = 120), and San Francisco (n = 168). There were significant differences in the proportion of deaths, mean age at seroconversion, and mean age at AIDS diagnosis in the three cohorts, but no significant differences in the reported use of zidovudine and Pneumocystis carinii pneumonia prophylaxis. Overall progression rates did not differ significantly across the cohorts: the median time to the development of AIDS was 122 months, and the median time from the initial AIDS diagnosis to death was 20 months. Multivariate proportional hazards analysis of progression from HIV-1 seroconversion to the development of AIDS found faster progression after June 1989. Multivariate proportional hazards analysis of progression from AIDS to death found younger age at diagnosis, an initial diagnosis of Kaposi's sarcoma, and more recent calendar time to be associated with slower progression. Multivariate proportional hazards analysis of progression from HIV-1 seroconversion to death found older age at seroconversion to be associated with faster progression. The 1987 expansion of the AIDS case definition, improved diagnostic methods, and more conscientious care-seeking behaviors may have resulted in diagnosis of AIDS at an earlier stage of HIV-1 infection, which would shorten the apparent time from seroconversion to progression to AIDS. This would also tend to increase survival after an initial AIDS diagnosis, which was observed in the more recent calendar periods, although such increases could also result from improved treatments and prophylaxis for HIV-1 disease. The time from seroconversion to death, a period not influenced by variations in diagnosing AIDS, lengthened only slightly in recent years. PMID- 8192141 TI - Concentration of indoor particulate matter as a determinant of respiratory health in children. AB - The effect of passive exposure to environmental tobacco smoke in the home on respiratory symptoms and pulmonary function level was studied in a cohort of white children aged 7-11 years examined in six US cities in 1983-1988. For 2,994 children with questionnaire-based exposure data, passive exposure to an additional pack of cigarettes smoked daily in the home was associated with increased incidence of lower respiratory symptoms (odds ratio (OR) = 1.25, 95% confidence interval (CI) 1.10-1.42). For 1,237 children with two consecutive 1 week measurements in both winter and summer, a 30-micrograms/m3 increase in the annual average indoor concentration of respirable particulate matter with an aerodynamic diameter of < 2.5 microns (PM2.5)--that is, approximately the effect of one pack per day of smoking--was marginally associated with an increased cumulative incidence of lower respiratory symptoms (OR = 1.13, 95% CI 0.99-1.30). Indoor measurements of PM2.5 showed no direct association with children's pulmonary function measurements. Children whose mothers smoked during pregnancy showed a reduction of -2.6% (95% CI -5.2% to 0.1%) in volume-adjusted forced expiratory flow rates. Therefore, current indoor exposure to PM2.5 increases the cumulative incidence of lower respiratory symptoms, but is only weakly associated with decreased pulmonary function level in preadolescent children. PMID- 8192142 TI - Medically treated miscarriage in Alamance County, North Carolina, 1988-1991. AB - The authors attempted to identify all medically treated miscarriages in Alamance County, North Carolina, between September 1988 and August 1991. Clinical and demographic characteristics of the cases were evaluated, and risks were calculated in relation to total pregnancies, including induced abortions. Miscarriage cases usually had positive pregnancy tests, and a sizable proportion (66% of whites, 72% of blacks) had a pathology report indicating the presence of a conceptus. Nineteen percent of the cases were identified in hospitals, a more common source for women who were unmarried, young, of low education, and had pregnancies of advanced gestational age. The risk of medically treated miscarriage was 7.7% among whites and 5.5% among blacks, with higher risks among older women. The lower risk among blacks, especially those with lower levels of education, suggests underascertainment, possibly resulting from a failure to seek treatment. PMID- 8192143 TI - Thiazides and bone mineral density in elderly men and women. AB - The relation of bone mineral density of the ultradistal radius, midshaft radius, hip, and lumbar spine to thiazide use were examined in a community-based sample of 1,696 white men and women aged 44-98 years. Male thiazide users had higher age adjusted bone mineral density levels only at the midshaft radius (p < 0.05). Among women, thiazide users had significantly higher bone mineral density levels at all four sites (p < 0.05), both before and after controlling for the effects of age, body mass index, smoking, and estrogen use. The association was explained by current thiazide use; no significant association was found between past use or duration of use and bone mineral density levels. Results were similar when hypertensive women were excluded from the analyses, suggesting the effect was drug-related and not due to hypertension or some other factor related to hypertension. At all sites, the highest bone mineral density levels were seen in women currently using both estrogen and thiazide. Overall, these findings suggest that thiazides may be useful in the prevention of osteoporosis in postmenopausal women. PMID- 8192144 TI - Validity of parental report of a child's medical history in otitis media research. AB - The authors compared parental reports with medical records for 157 children enrolled in a prospective study of chronic otitis media with effusion between 1987 and 1991. Parents completed a questionnaire about the child's past health history, and the research nurse abstracted history information from the clinic's medical record. Previous insertion of a tympanostomy tube (kappa = 0.96) and premature birth (kappa = 0.68) were accurately reported, but there was a substantial proportion of missing data for age at first episode of otitis media, occurrence of otitis media the previous summer, and number of episodes in the previous 18 months. Data were significantly more likely to be missing for male children, children with siblings, and those with more episodes. Parents who reported six or more previous episodes for their child overestimated the number compared with the medical record (8.7 vs. 7.4, respectively; p = 0.01), while those who reported fewer episodes underestimated the number (3.1 vs. 4.6, respectively; p = 0.01). Episodes of otitis media during the 3 months between study visits were also accurately reported (kappa = 0.94). The accuracy and completeness of parental report of the child's health history was influenced by the chronicity of otitis media, the duration of recall, and the seriousness of the event being recalled. PMID- 8192145 TI - Increased binding of Sp1 to the gamma-globin gene promoter upon site-specific cytosine methylation. AB - We have studied the effect of site-specific cytosine methylation on the binding of nuclear proteins to the gamma-globin promoter region from -71 to -34. This sequence was recently shown to contain a stage selector element responsible for increased transcription from the gamma compared to the beta promoter when both are linked to Locus Control Region enhancer sequences. We observed that Sp1 binding to this sequence is increased upon site-specific cytosine methylation, such that only methylation of the cytosine in the -50 CpG dinucleotide effects Sp1 binding. Methylation of the distal C of the Hpall site has no effect. The possible functional role of Sp1 as a repressor of gamma-globin synthesis is discussed. PMID- 8192146 TI - Connective tissue components in serum in multiple myeloma: analyses of propeptides of type I and type III procollagens, type I collagen telopeptide, and hyaluronan. AB - The present study was performed to evaluate whether information concerning synthesis and degradation of type I collagen in multiple myeloma (MM) as obtained by serum analyses of C-terminal propeptide of type I procollagen (PICP) and the C terminal telopeptide of type I collagen (ICTP) may be useful in evaluating the development of osteolytic bone destruction. Serum N-terminal propeptide of type III procollagen (PIIINP) may give information about marrow fibrosis in MM. No data are available about MM and serum hyaluronan, another important component of bone marrow stroma. We examined 15 consecutive patients before treatment and 15 sex- and age-matched controls. We found highly significant elevations in serum ICTP (median 6.2 vs. 2.4 micrograms/L; P < 0.01), PIIINP (median 5.2 vs. 2.9 micrograms/L; P < 0.01) and hyaluronan (median 122 vs. 45 micrograms/L; P < 0.01). ICTP in serum correlated closely to bone morbidity (r = 0.69; P < 0.01). Furthermore, serum ICTP correlated highly significantly to serum PIIINP (P < 0.01) and serum beta 2-microglobulin (P < 0.01), whereas there was no correlation between hyaluronan and any of the collagen-derived peptides or beta 2 microglobulin. The MM group was followed for 9-25 months and analysis of survival data suggested that serum ICTP may be of predictive value (P < 0.05). We conclude that important changes in connective tissue metabolism occur in MM. ICTP in serum seems to be a noninvasive marker of bone morbidity and may be of prognostic value. Furthermore, elevation of hyaluronan in serum is common in MM, the significance of which is unknown. PMID- 8192147 TI - Rapid improvement of coagulopathy by all-trans retinoic acid in acute promyelocytic leukemia. AB - Treatment of acute promyelocytic leukemia (APL) patients with all-trans retinoic acid (ATRA) was associated with rapid improvement in hemostatic markers. We made serial analyses of various hemostatic parameters in seven newly diagnosed APL patients. In all patients at diagnosis, plasma fibrinogen/fibrin degradation product (fragment-E), cross-linked fibrin degradation product (D-dimer fragment), thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex were elevated, indicating the presence of disseminated intravascular coagulation (DIC). Antithrombin III (ATIII) levels were normal in all patients except for the patient with congenital ATIII deficiency. In four patients subsequently treated with ATRA without anticoagulant therapy, these hemostatic markers returned to near-normal levels by day 7 of treatment, indicating that DIC was essentially resolved. By contrast, in three patients who received conventional chemotherapy with a continuous low-dose heparin, improvement of coagulopathy was slower than in patients treated with ATRA. These results suggest that ATRA therapy exerts the rapid improvement in abnormal hemostatic markers in APL patients without any anticoagulant therapies, by inducing differentiation of leukemic cells and, in turns no massive release of procoagulant or fibrinolytic substances from these cells. PMID- 8192148 TI - Recombinant tissue plasminogen activator (rt-PA) for veno-occlusive liver disease in pediatric autologous bone marrow transplant patients. AB - The pathogenesis of veno-occlusive disease (VOD) of the liver appears to be secondary to endothelial damage of terminal hepatic venules, which leads to activation of the coagulation cascade, fibrin deposition, and eventual fibrous obliteration of the hepatic venules. Patients with VOD usually present with jaundice, hepatomegaly, weight gain, and ascites. This complication is usually associated with a high mortality rate. We report here the frequency and treatment of VOD in our autologous bone marrow transplant (BMT) patient population. Three of 15 (20%) children (median age 9 years) developed VOD and were treated with recombinant tissue plasminogen activator (rt-PA). Two of these three patients were prepared for BMT with busulfan (16 mg/kg) and cyclophosphamide (Cytoxan, 200 mg/kg), while the other child received cytosine arabinoside (ARA-C 18 g/m2), Cytoxan (3,600 mg/m2) and total body irradiation (TBI, 1,400 y). VOD developed between days 7-24 posttransplant. Clotting studies obtained pretransplant and during VOD included prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin-degradation product (FDP), proteins C and S, and platelet count. There was no correlation between the incidence of VOD and coagulation status. All patients had normal pretransplant clotting studies. However, protein C levels were noted to be consistently low for those patients at the time of VOD. All three patients received rt-PA at a dose of 0.25-0.5 mg/kg for 4 days. This dose produced increased levels of FDP but did not significantly prolong PT nor PTT. Two of the patients had dramatic responses and had complete resolution of VOD within 6-12 days from the start of therapy. The other patient died of fulminant hepatic failure. It seems that rt-PA is effective in VOD of the liver, which may be associated with low protein C level. PMID- 8192149 TI - 1-Deamino-8-D-arginine vasopressin (DDAVP) increases platelet membrane expression of glycoprotein Ib in patients with disorders of platelet function and after cardiopulmonary bypass. AB - 1-deamino-8-D-Arginine vasopressin (DDAVP) shortens the bleeding time in some patients with platelet dysfunction and decreases blood loss in some cardiopulmonary bypass patients. We studied platelet membrane glycoproteins in patients with von Willebrand disease (vWD), disorders of platelet function, and in cardiopulmonary bypass patients after infusion of 0.3 microgram/kg of DDAVP. Platelets from 8 cardiopulmonary bypass patients, receiving DDAVP immediately after surgery, were compared to those of 14 patients not receiving DDAVP. We also studied 12 patients with vWD, and 8 patients with platelet dysfunction receiving DDAVP. Fixed platelets, stained with monoclonal fluorescein (FITC)-labeled antibodies directed against GPIb (CD42b antigen), GPIb/IX, GPIIb/IIIa (CD41a antigen), CD63 antigen (a platelet activation protein), and P-selectin (CD62 antigen) were studied by flow cytometry. Binding of CD42b monoclonal antibody (MoAb) and anti-GPIb/IX to platelets from both groups of bypass patients increased during the 18-20 hr after surgery, but the group receiving DDAVP showed the greater increase (P = 0.032). Platelets from patients receiving DDAVP for vWD or for platelet dysfunction, had increases in CD42b MoAb and anti-GPIb/IX binding (P < 0.01) that coincided with shortening of their bleeding time. No changes were seen in binding of other antibodies. When platelets from normal donors were incubated with DDAVP for 20 hr, there were increases in platelet surface CD42b MoAb binding, while immunogold-stained transmission electron micrographs of permeabilized platelets demonstrated decreases in cytoplasmic CD42b MoAb binding. DDAVP increases platelet membrane GPIb expression in a variety of patients and may account for improvement in hemostasis seen in some studies. Redistribution of GPIb from the cytoplasm to the membrane may account for this increased expression. PMID- 8192150 TI - Detection of common deletional alpha-thalassemia-2 determinants by PCR. AB - We have developed a rapid approach to detect the two most common alpha thalassemia-2 (alpha-thal-2) determinants by the polymerase chain reaction (PCR) technique, which takes a few hours to complete. Specific oligonucleotides selectively amplify appropriate segments of the chromosome with the deletion and the normal chromosome under identical experimental conditions, and the products are identified by electrophoresis on 1.5% agarose. Characterization of the two most prevalent types of the -alpha 3.7 determinant [-alpha 3.7(I) and -alpha 3.7(II)] can be made by Apa I digestion of the PCR product. Two types of alpha thal-2 determinants, -alpha 3.7 and -alpha 4.2, were tested in numerous samples from various parts of the world. This approach is believed to provide a cost effective way to screen large numbers of blood samples in a relatively short time and can be used to identify alpha-thal-2 heterozygotes and homozygotes and compound heterozygotes (-alpha 3.7/-alpha 4.2) in populations where such alpha gene defects are shown to exist at high frequencies. PMID- 8192151 TI - Increased thrombosis incidence in a family with an inherited protein S deficiency and a high oxygen affinity hemoglobin variant. AB - Inherited protein S deficiency and the presence of a rare high oxygen affinity hemoglobin variant: Hb Rainier [beta 145 (HC2) Tyr-->Cys] were found in a family. Among 16 studied members, nine were found as carriers of protein S deficiency (type I with decrease of total, free, and activity levels). Six subjects carried the high-affinity hemoglobin variant, which displayed an increase of blood viscosity. Four members combined both abnormalities. Three had thrombotic accidents before the age of 30. We suggest the combination of protein S deficiency and the presence of this hemoglobin variant can lead to a severe primary hypercoagulable state with pathological consequences compared to each genetic defect alone. PMID- 8192152 TI - Gray platelet syndrome with splenomegaly and signs of extramedullary hematopoiesis: a case report with review of the literature. AB - Gray platelet syndrome (GPS) is a rare bleeding disorder characterized by thrombocytopenia, agranular gray platelets in blood films, and almost total absence of platelet alpha-granules and their constituents. We describe here a rare case of GPS with myelofibrosis and splenomegaly indicating extramedullary hematopoiesis. Splenectomy was followed by normalization of platelet count but the bleeding diathesis continued. Based on a follow-up of more than 15 years, the slight myelofibrosis in our patient seems to be non-progressive. We also summarize the major clinical and laboratory features of previously published cases of GPS in order to obtain more comprehensive understanding of this rare disorder. From the clinical point of view, the bleeding tendency in this syndrome generally varies from mild to moderate, and no specific treatment is usually needed. Careful examination of peripheral blood films is necessary for the diagnosis of this rare syndrome. PMID- 8192153 TI - Familial myeloproliferative syndrome. AB - Familial chronic myeloproliferative syndrome (CMS) was observed in five members from two different generations of the same kindred. Diagnosis included agnogenic myeloid metaplasia (case 1), polycythemia vera (case 2), and essential thrombocythemia (cases 3-5). Cases 1-3 were siblings, case 5 was the daughter of case 1, and case 4 was the cousin of cases 1, 3. Age at diagnosis ranged from 28 to 75 years, cases 1 and 3 were male, and the others were female. The diagnosis was made after an episode of cerebral thrombosis in one patient, during a study for headache and dizziness in another, and fortuitously in the three remainders. All patients had splenomegaly and varying degrees of thrombocytosis. The cytogenetic exam was normal in all four cases. A woman patient was treated with interferon during a pregnancy. Fetal growth was retarded, and the newborn showed bone and genital malformations. No environmental leukemogen factor was found. This familial case strengthens Dameshek's theory of a common pathogenesis of CMS and suggests a genetic and hereditary etiology. PMID- 8192154 TI - ProMACE day 1/MOPP day 8 chemotherapy for prolymphocytic leukemia: a case report of prolonged survival. AB - The treatment result of a case of de novo B-cell prolymphocytic leukemia (B-PLL) is described. The diagnosis was established with histologic, ultrastructural and immunologic studies. The patient was treated with chemotherapy using a total of seven cycles of ProMACE Day 1/MOPP Day 8 lymphoma regimen. Complete remission was achieved after 5 cycles of chemotherapy. The patient remains disease free after a 7-year follow up. This is the first case of PLL being treated with such a regimen and the only case reported achieved such prolonged survival. Results of other treatment modalities are reviewed. PMID- 8192155 TI - Congenital coagulopathies and pregnancy: report of four pregnancies in a factor X deficient woman. AB - Pregnancy in women with congenital coagulation factor deficiencies has been associated with adverse fetal outcomes. Recurrent spontaneous abortions, placental abruptions, and premature births are reported, the exact reasons for which are not clear, and management of such patients continues to be a challenge. We reviewed the outcome of four pregnancies in a patient with factor X deficiency, and looked at the effect of factor replacement therapy on pregnancy. Her first two pregnancies resulted in the birth of extremely premature babies at 21 and 25 weeks of gestation, both of which died in the neonatal period. The patient was treated with fresh frozen plasma for acute bleeding episodes during these pregnancies. In addition during her second conception she was given factor IX complex [Konyne] prophylactically, but only in the latter half of her pregnancy. During her next two pregnancies she was treated early on during pregnancy, with prophylactic replacement of factor X. She delivered healthy babies at 34 and 32 weeks of gestation, and they are both doing well. We therefore suggest possible mechanisms by which aggressive prophylactic factor support in a female with severe congenital coagulopathy, may improve on fetal outcome. PMID- 8192156 TI - Hemoglobinopathies in the Dogon Country: presence of beta S, beta C, and delta A' genes. AB - The population of the Dogon, located in Mali, is divided in an endogamic Noble class and two endogamic servant castes (Tanners and Blacksmiths). We find that the polymorphic frequencies of beta c, beta S, and, unexpectedly, a mutation of the delta-chain (delta A'), are geographically (valley vs. plateau) as well as social status dependent. PMID- 8192157 TI - Author's reply to "Rearrangement of the BCR/ABL and TCR-beta genes in lymph node blast crisis diagnosed of chronic myeloid leukemia". PMID- 8192158 TI - About ITP. PMID- 8192159 TI - Possible causal relationship between essential thrombocythemia and concomitant monoclonal gammopathy: report of two cases. PMID- 8192160 TI - Fatal intravascular hemolysis induced by platelet concentrate. PMID- 8192161 TI - Cellulose-treated blood is a good source of DNA for molecular analysis. PMID- 8192162 TI - Familial macrocytosis. PMID- 8192163 TI - Glutathione peroxidase activities in serum and cerebrospinal fluid from patients with acute lymphocytic leukemia. PMID- 8192164 TI - Von Willebrand's disease, digestive angiodysplasia, and estrogen-progesterone treatment. PMID- 8192165 TI - Corticosteroid effect on factor VIII. PMID- 8192166 TI - Treatment of childhood chronic ITP. PMID- 8192167 TI - Diagnostic value of clonality of surface immunoglobulin light and heavy chains in malignant lymphoproliferative disorders. PMID- 8192168 TI - Epstein-Barr virus-associated Hodgkin's disease following renal transplantation. PMID- 8192169 TI - Combinations of drugs in lipid-lowering therapy. PMID- 8192170 TI - Efficacy and safety of a combination fluvastatin-bezafibrate treatment for familial hypercholesterolemia: comparative analysis with a fluvastatin cholestyramine combination. AB - PURPOSE: Familial hypercholesterolemia (FH) carries a markedly increased risk for coronary artery disease (CAD). Reduction of plasma low-density lipoprotein cholesterol (LDL-C) levels to the normal range may prevent premature atherosclerosis and usually requires a combination of cholesterol-lowering drugs. The major objective of this study is to compare two different drug combinations for the treatment of heterozygous FH. PATIENTS AND METHODS: The current investigation is a short-term, double-blind study comparing the efficacy and safety of fluvastatin when combined with cholestyramine (group 1) or with bezafibrate (group 2) in 38 patients with heterozygous FH. RESULTS: After 6 weeks of combination treatment, in comparison to a drug-free baseline (patients receiving single-blind placebo during the lead-in period of an earlier study, ie, before ever receiving fluvastatin), the combination of 40 mg/d of fluvastatin with 400 mg/d of bezafibrate in group 2 reduced plasma LDL-C levels by 35% as compared with 32% in group 1, and reduced the LDL-C/high-density cholesterol (HDL C) ratio by 46%, compared to 37% in group 1 (a non-significant difference for both comparisons). When compared to an intermittent 6-week open-label administration of 40 mg fluvastatin monotherapy, the addition of cholestyramine or bezafibrate each reduced LDL-C by an additional 13% (P < 0.01 for both regimens). CONCLUSIONS: Fluvastatin-bezafibrate is superior to a fluvastatin cholestyramine combination for lowering serum triglycerides and elevating HDL-C serum levels in patients in conjunction with a significant lowering of LDL-C/HDL C ratios, and may be an effective synergistic therapy for heterozygous FH. No episodes of myositis were seen in this short-term study, a finding that is in agreement with most of the reported studies on statin-fibrate combinations reviewed here. PMID- 8192172 TI - The development of cytomegalovirus encephalitis in AIDS patients receiving ganciclovir. AB - PURPOSE: Cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS) requires lifelong therapy with either intravenous ganciclovir sodium or foscarnet sodium. From June 1989 through February 1992, seven patients with AIDS were diagnosed to have CMV retinitis, and all were treated with ganciclovir. Five of the seven developed abrupt preterminal mental status changes. All five with mental status changes received anti-CMV therapy until the time of death. Autopsies were performed in all cases to determine the cause of mental status changes. PATIENTS AND METHODS: Five patients with AIDS and newly diagnosed CMV retinitis. Retrospective case analyses with autopsies. All five patients were treated with gangciclovir immediately upon the diagnosis of CMV retinitis and received ganciclovir at standard dosages until death. RESULTS: Four patients had clinically stable retinitis throughout the entire course of ganciclovir therapy. In the fifth patient, because of fundoscopic deterioration, foscarnet therapy was initiated 1 month prior to death. Cerebrospinal fluid analysis and magnetic resonance imaging, although abnormal, were not diagnostically specific. Neuropathologic examination revealed fulminant diffuse CMV encephalitis in all patients, with prominent ependymal and periventricular necrosis. CONCLUSIONS: These results suggest that while ganciclovir therapy may clinically stabilize CMV retinitis in patients with AIDS, it does not appear to prevent the development of, or be effective in the treatment of, CMV encephalitis. Thus, clinicians should consider the diagnosis of CMV encephalitis in patients receiving ganciclovir who develop mental status changes and, if possible, alter therapy accordingly. PMID- 8192171 TI - Osmotic demyelination syndrome following correction of hyponatremia: association with hypokalemia. AB - The osmotic demyelination syndrome (ODS) is a neurologic complication associated with rapid correction of hyponatremia. A case is described in which the patient was found to have hypokalemia as well as hyponatremia prior to the development of ODS. The literature was reviewed for cases of ODS in which patients had hyponatremia (serum sodium < or = 126 mmol/L) at presentation followed by correction of the hyponatremia. Of the 74 cases in which serum sodium and serum potassium values were reported at the time of presentation, 66 patients (89%) had hypokalemia. In 20 of these cases, serial measurements of sodium and potassium were reported, and in no instance was the potassium level normalized prior to the time of most rapid correction of the serum sodium. Hypokalemia may predispose patients to develop osmotic demyelination following correction of hyponatremia. The etiology of this complication is unclear. In neurologically stable patients with severe hyponatremia, it may be beneficial to correct hypokalemia prior to correction of the serum sodium. This maneuver may further reduce the incidence of ODS. PMID- 8192173 TI - Efficacy and safety of 0.5% podofilox solution in the treatment and suppression of anogenital warts. AB - PURPOSE: For the patient-administered treatment of anogenital warts, 0.5% podofilox (podophyllotoxin), one of the active compounds of podophyllin, has been shown to be more effective than the vehicle alone. This study was designed to evaluate the safety and efficacy of 0.5% podofilox treatment followed by prophylaxis. PATIENTS AND METHODS: A total of 103 patients were entered in stage 1 of the study. Stage 1 was an open label study, and patients self-administered 0.5% podofilox twice daily for 3 consecutive days per week for 4 weeks. A total of 100 patients remained available for efficacy and safety analyses. At the end of stage 1, patients who had a complete response proceeded to stage 2 of the study. Patients who had a 50% to 99% reduction in measured total wart area were offered cryotherapy every 10 days, up to 5 times. If cleared of warts, they were also entered into stage 2. A total of 57 patients were enrolled into stage 2, a double-blind, randomized, placebo-controlled prophylactic study of 0.5% podofilox self-administered once daily for 3 days per week for 8 weeks, on the sites of healed warts. A total of 45 patients in stage 2 were available for efficacy analysis. RESULTS: By the end of stage 1, 68% of the warts had disappeared, and 29 of 100 patients (29%) had a complete response. A total of 49 patients had a 50% or greater improvement in wart area and underwent cryotherapy. Rates of local side effects after 1 week of treatment were 57% for inflammation, 39% for erosion, 47% for pain, 48% for burning, and 44% for itching. However, these symptoms and signs were mostly mild to moderate in intensity and diminished over time. Therefore, overall treatment was well tolerated. In stage 2, only 4 of 21 patients (19%) in the podofilox group experienced a recurrence as opposed to 12 of 24 (50%) in the placebo group (P = 0.031). As in stage 1, the side effects were modest, and the drug was well tolerated. CONCLUSION: This study confirms the efficacy and good tolerance of 0.5% podofilox in the treatment of anogenital warts. It also establishes the safety and superior efficacy of patient administered podofilox over the vehicle alone as prophylaxis against recurrence of lesions. Although long-term efficacy and tolerance remain to be established, podofilox appears to be a useful agent in the control of this disease. PMID- 8192174 TI - Incidence of hospitalization for digitalis toxicity among elderly Americans. AB - OBJECTIVE: To document the prevalence of digitalis use and the incidence of hospitalization caused by digitalis toxicity. DESIGN: Observational cohort followed for 6 years. SETTING: Urban community. PARTICIPANTS: Persons were eligible if they were (1) enrolled in the Yale Health and Aging Project and (2) using digitalis when interviewed in 1982 or 1985. The Project comprises a sample of noninstitutionalized persons aged 65 years and over living in New Haven, Connecticut. METHODS: Between 1982 and 1988 when a Project participant was hospitalized in New Haven, a researcher reviewed the medical record and coded up to 16 International Classification of Diseases-Class 9 (ICD-9) diagnoses. To identify hospitalizations caused by digitalis, we reexamined records with ICD-9 codes suggesting toxicity. We confirmed the admission illness was an adverse drug reaction with a decision algorithm. RESULTS: The prevalence of digitalis use was 13% in 1982 and 12% in 1985. The incidence of hospitalization caused by definite or probable toxicity was 4.2% (95% confidence interval = 0.3% to 8.1%) over 6 years. Manifestations of toxicity were malaise or gastrointestinal symptoms (two patients) and heart block plus malaise or gastrointestinal symptoms (six patients). Use of quinidine was associated (P < .05) with toxicity. CONCLUSION: Knowledge about the incidence of severe, morbid toxicity may help clinicians estimate and compare the risks and benefits of digitalis and alternate therapies. PMID- 8192175 TI - More talk, less paper: predicting the accuracy of substituted judgments. AB - PURPOSE: To study the accuracy of substituted judgments regarding life-sustaining therapies and other therapies made by surrogate decision makers and to investigate factors associated with more accurate predictions. PATIENTS AND METHODS: A total of 50 pairs of ambulatory patients and surrogates, chosen according to a legal hierarchy, underwent separate interviews in which surrogates were asked to predict the preferences of patients for eight modes of medical therapy in three clinical scenarios, given only yes or no as response options. Patient preferences, their surrogates' predictions, and the extent of agreement between the two were measured. The total number of correct predictions constituted the Surrogate Accuracy in Matching Patient Preferences Scale (SAMPPS). Sociodemographic factors associated with agreement were also assessed. RESULTS: Agreement between patients and surrogates ranged from 57% to 81%. The mean SAMPPS score was 17 of 24 correct. Kappa (k) coefficients, which measure inter-rater concordance, were positive for 23 of 24 items and were 0.3 or greater (P < 0.05) for 14 of 24 items. Rates of agreement were not related to whether the surrogate interviewed (surrogate determined by state law) was the person the patient would have chosen as a surrogate or whether the patient had an advance directive. In multiple linear regression analysis, both prior discussions of preferences and nonchurchgoing behavior were significantly associated with patient-surrogate agreement, independent of religious denomination and race. CONCLUSION: When pressed to choose, surrogates can predict the preferences of patients for life-sustaining therapies with an imperfect accuracy that nonetheless significantly exceeds the agreement expected due to chance alone. Exhorting surrogates to give their "best estimate" and encouraging prior discussions may improve accuracy. Houses of worship might be important target sites for campaigns to improve public awareness about advance directives. PMID- 8192176 TI - Tuberculosis and acquired immunodeficiency syndrome: a historical perspective on recent developments. AB - The incidence of tuberculosis has increased in recent years, at least in part as a result of the ongoing worldwide epidemic of acquired immunodeficiency syndrome (AIDS). In addition, the occurrence of outbreaks caused by multidrug-resistant Mycobacterium tuberculosis organisms has greatly heightened concern. In retrospect, a number of seminal studies that have appeared during the past decade have helped to define changing concepts concerning the epidemiology, pathogenesis, approaches to preventive care, diagnosis, and treatment of tuberculosis in HIV-infected persons. Such reports have shown that the variable clinical manifestations of tuberculosis in patients with AIDS are greatly influenced by the degree of HIV-induced immunosuppression. Explosive outbreaks of tuberculosis occurring in closed environments have emphasized that patients with AIDS and pulmonary tuberculosis may be highly contagious, especially when diagnosis and implementation of appropriate infection control measures are delayed. The extent to which homelessness and illicit drug use complicate management of tuberculosis have been examined, and the high risk of persons who are both tuberculin-positive and HIV-positive ultimately developing active tuberculosis, unless chemoprophylaxis is completed, has been clearly shown. The utility of sputum smears, bronchoscopy, and newer technologies such as polymerase chain reaction for diagnosis has been examined. The risk of relapse appears to be low when patients with AIDS with drug-sensitive tuberculosis complete appropriate multiple-drug therapy. Recent reports have addressed important hospital infection control, tuberculin testing, and chemoprophylaxis issues. This paper describes this evolution of understanding, focusing on reports that we believe have been conceptually important. PMID- 8192177 TI - Risks of angiotensin-converting enzyme inhibition during pregnancy: experimental and clinical evidence, potential mechanisms, and recommendations for use. AB - OBJECTIVE: To review reports on the use of angiotensin-converting enzyme inhibitors (ACE-I) during pregnancy in order to determine the incidence, nature, and potential mechanisms of fetal complications in an attempt to establish recommendations related to the use of these drugs during gestation. DATA SOURCES: Relevant English-language articles identified through a Medline search and bibliographies found in recent articles. STUDY SELECTION: Large number of reports both on animals and on humans have consistently shown a high degree of morbidity and even mortality in fetuses or newborns exposed to ACE-I during pregnancy. The reported complications include oligohydramnios, intrauterine growth retardation, premature labor, fetal and neonatal renal failure, bony malformations, limb contractures, persistent patent ductus arteriosus, pulmonary hypoplasia, respiratory distress syndrome, prolonged hypotension, and neonatal death. A high incidence of fetal complications was related to the use of ACE-I at all trimesters of pregnancy. CONCLUSION: The gestational use of ACE-I may be associated with a high degree of fetal and newborn morbidity and even mortality. The use of these drugs should be avoided at all trimesters of pregnancy. PMID- 8192178 TI - Age and sex associations of 40 autoimmune diseases. AB - Self-injury by the host's immune system is believed to be a factor in the etiology of many diseases. Much attention has been given to the part played by sex hormones in such processes. Current literature frequently maintains that females are more susceptible than males to autoimmune diseases. In order to gain information about this factor, a tabulation has been made of the sex incidence of 40 autoimmune diseases which occur at different periods of life: childhood, early adult life, mature adult life, and old age. To some extent the tabulations substantiate female preponderance, but in some there is no gender difference, and in others, particularly the autoimmune nephropathies, male preponderance is the rule. Findings in experiments with animal analogues of human autoimmune disease, showing that administration of estrogen augments the manifestations, whereas androgen treatment suppresses them, do not correlate closely with clinical experience. PMID- 8192179 TI - A fourth year of training in ambulatory medicine: the University of Washington experience. AB - Postresidency training in ambulatory general internal medicine has been proposed as a means to enhance the generalist skills of internal medicine graduates. At the University of Washington, a fourth year of training in ambulatory medicine has been offered since 1967. The resident training year provides a core experience in general internal medicine as well as the opportunity for elective experiences in subspecialties and other allied specialties. Graduates of this year of experience in ambulatory training were surveyed to determine current practice patterns and retrospective evaluation of the program; responses were received from 36 of 52 graduates (69%). Among respondents, 50% are general internists, 39% subspecialists, and 11% in other practice specialties. Eight respondents (22%) are practicing in rural communities. Respondents identified the specialized training in outpatient medicine as the primary strength of the additional training year. Many reported using the year to gain additional training tailored to their future practice. The fourth year of ambulatory training thus represents an efficient means to provide additional training to internists planning careers in general internal medicine. It can serve a variety of purposes, including preparation for practice in rural and other settings with unique clinical demands, training of clinician educators, and retraining of subspecialists seeking to shift to generalist practice. PMID- 8192180 TI - Nausea and vomiting in a 69-year-old man following cholecystectomy. PMID- 8192181 TI - Streptococcus sanguis bacteremia during ciprofloxacin therapy of a diabetic foot ulcer. PMID- 8192182 TI - Impaired resolution of massive pulmonary embolism associated with an inhibited fibrinolytic response. PMID- 8192183 TI - American Journal of Psychiatry celebrates 150th anniversary. PMID- 8192184 TI - The moral treatment of insanity. 1847. PMID- 8192185 TI - Katatonia, a clinical form of insanity. 1877. PMID- 8192186 TI - The curability of insanity. A statistical study. 1885. PMID- 8192187 TI - Personality changes and upheavals arising out of the sense of personal failure. 1926. PMID- 8192188 TI - The onset of schizophrenia. 1927. PMID- 8192189 TI - In memoriam: Emil Kraepelin. 1927. PMID- 8192190 TI - The acute schizoaffective psychoses. 1933. PMID- 8192191 TI - Symptomatology and management of acute grief. 1944. PMID- 8192192 TI - Gheel. 1851. PMID- 8192193 TI - Irrelevant and metaphorical language in early infantile autism. 1946. PMID- 8192194 TI - The importance of a correct physiology of the brain, as applied to the elucidation of medico-legal questions; and the necessity of greater accuracy and minuteness in reporting post mortem examinations. 1845. PMID- 8192195 TI - Statistics of insanity. 1849. PMID- 8192196 TI - A review of the signs of degeneration and of methods of registration. 1896. PMID- 8192197 TI - Influenza and schizophrenia. An analysis of post-influenzal "dementia precox," as of 1918, and five years later further studies of the psychiatric aspects of influenza. 1926. PMID- 8192198 TI - The genetic theory of schizophrenia. An analysis of 691 schizophrenic twin index families. 1946. PMID- 8192199 TI - The concepts of "meaning" and "cause" in psychodynamics. 1947. PMID- 8192200 TI - A sketch of the history, buildings, and organization of the Pennsylvania Hospital for the Insane, extracted principally from the reports of Thomas S. Kirkbride, M.D., physician to the institution. 1845. PMID- 8192201 TI - Cerebral blood flow and metabolism in schizophrenia. The effects of barbiturate semi-narcosis, insulin coma and electroshock. 1948. PMID- 8192202 TI - Research and its support under the National Mental Health Act. 1949. PMID- 8192203 TI - Observations on the medical treatment of insanity. 1850. PMID- 8192204 TI - The history of the malaria treatment of general paralysis. 1946. PMID- 8192205 TI - Prefrontal leucotomy in the treatment of mental disorders. 1937. PMID- 8192206 TI - The methodical use of hypoglycemia in the treatment of psychoses. 1937. PMID- 8192207 TI - Curare: a preventive of traumatic complications in convulsive shock therapy (including a preliminary report on a synthetic curare-like drug). 1941. PMID- 8192208 TI - The society of Alcoholics Anonymous. 1949. PMID- 8192209 TI - The use of antabuse (tetraethylthiuramdisulphide) in chronic alcoholics. 1950. PMID- 8192210 TI - Chlorpromazine treatment of mental disorders. 1955. PMID- 8192211 TI - Clinical findings in the use of Tofranil in depressive and other psychiatric states. 1959. PMID- 8192212 TI - The use of lithium in the affective psychoses. 1966. PMID- 8192213 TI - Address before the Fiftieth Annual Meeting of the American Medico-Psychological Association, held in Philadelphia, May 16th, 1894. PMID- 8192214 TI - Some remarks on the address delivered to the American Medico-Psychological Association, by S. Weir Mitchell, M.D., May 16, 1894. PMID- 8192215 TI - A short sketch of the problems of psychiatry. 1897. PMID- 8192216 TI - The attitude of neurologists, psychiatrists and psychologists toward psychoanalysis. 1939. PMID- 8192217 TI - Some trends of psychiatry. 1944. PMID- 8192218 TI - Benjamin Rush and American psychiatry. 1944. PMID- 8192219 TI - The role of psychiatry in the world today. 1947. PMID- 8192220 TI - Current trends in German psychiatry. 1949. PMID- 8192221 TI - Reminiscences: 1938 and since. AB - The author cites significant changes in the conduct of the psychiatric profession between the fourth and ninth decades of this century. Determinants of the changes included the impact of World War II, the National Mental Health Act of 1946, the evolution of multiple modes of psychotherapy, the move from a system of involuntary incarceration and treatment in public institutions to a voluntaristic and pluralistic system, the provision of public and private insurance support for office, outpatient, and inpatient psychiatric care, the resurgence of psychopharmacology, and the pursuit of research in biological and psychosocial fields. The social goals of the profession are also discussed. PMID- 8192222 TI - Asylums exclusively for the incurable insane. 1844. PMID- 8192223 TI - Definition of insanity--nature of the disease. 1844. PMID- 8192224 TI - [The role of rh-erythropoietin in the scope of blood transfusion sparing methods. Proceedings of the symposium on Innovative Aspects of Clinical Medicine. Heidelberg, 3-5 December 1993]. PMID- 8192225 TI - Determination of octadecadienoic acids in human serum: a critical appraisal. AB - The method based on high-performance liquid chromatography currently used to determine the lipid levels of octadeca-9(Z),11(E)-dienoic acid in human serum fails to distinguish between this acid and octadeca-10(E),12(Z)-dienoic acid. Adducts with the fluorescent dienophile 4-[3-(1-propenyl)propyl]-1,2,4-triazoline 3,5-dione permit the separation of these two isomeric acids as does gas-liquid chromatography of their methyl esters, but these alternatives produce equivocal results when applied to biological samples. PMID- 8192226 TI - Determination of free myo-inositol in milk and infant formula by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method is described for the determination of supplemental myo-inositol in infant formulas based on cows' milk. The technique incorporates pre-column derivatization with phenylisocyanate followed by reversed-phase gradient chromatography and ultraviolet detection. The protocol was also applied to a survey of free inositol at endogenous levels in the milk of cows, goats and humans. Nutritional preparations containing inositol at pharmacological levels are also amenable to a simplified isocratic analysis. PMID- 8192227 TI - Determination of 2,2,2-trichloroethanol in plasma and urine by ion-exclusion chromatography. AB - A simple and rapid chromatographic method has been developed for the determination of 2,2,2-trichloroethanol (TCEOH) and its glucuronide in plasma and urine. A glass column (150 x 6.6 mm i.d.) packed with Aminex A-5 cation-exchange resin (potassium form) following the slurry method was used as the analytical column, and an admixture of 10 mmol l-1 potassium sulfate and 10 mmol l-1 potassium hydroxide solution as the eluent (pH 12.2). Diluted plasma samples and urine samples were directly injected into the chromatograph through a 0.45 micron membrane filter without deproteinization. The amount of TCEOH conjugated to glucuronide was determined following treatment with beta-glucuronidase (200 U) for 30 min at 37 degrees C. This allowed the concentration of free, total, and conjugated TCEOH to be determined. The calibration graph was rectilinear from 5 to 500 mg l-1 of TCEOH, with a detection limit of 3 mg l-1, 2 sigma, being the signal-to-noise ratio. The analytical recovery of TCEOH, obtained by analysing spiked plasma and urine samples, was in the range 98.4-102% and the relative standard deviation was less than 3.5%. PMID- 8192228 TI - Thin-layer chromatographic spray reagent for the screening of biological materials for the presence of carbaryl. AB - A spray reagent for the detection of the carbamate insecticide carbaryl was developed, consisting of 1% ammonium cerium(IV) nitrate in 20% v/v hydrochloric acid. This reagent reacts with the hydrolysis product of carbaryl, 1-naphthol, and forms a violet complex. Other carbamate insecticides do not give similar coloured spots. Moreover, organophosphorus, organochlorine and pyrethroid insecticides and constituents of visceral extracts (amino acids, peptides, proteins, etc.) do not interfere. The sensitivity of the reagent is about 0.1 microgram. PMID- 8192229 TI - Competitive enzyme-linked immunosorbent assay for the determination of zinc bacitracin in animal feedingstuffs. AB - Traditionally, bioassay has been the chosen technique for the determination of bacitracin compounds in animal feedingstuffs. However, detection and determination of this antibiotic have given problems when it is present at low levels. A competitive enzyme-linked immunosorbent assay (ELISA) by which it is possible to detect both bacitracin and zinc bacitracin at levels as low as 1 mg kg-1 in animal feeds is described. The ELISA technique has been used in this laboratory to monitor samples from a drug stability storage trial for the presence of zinc bacitracin. In addition, individual polypeptide components of zinc bacitracin have been separated by high-performance liquid chromatography. Fractions were collected and tested by the ELISA technique to assess the response between individual components and the primary antibody. The response was compared with known microbiological activity. PMID- 8192230 TI - Development of an enzyme-linked immunosorbent assay for isoproturon in water. AB - A competitive enzyme-linked immunosorbent assay (ELISA) suitable for the determination of the urea herbicide isoproturon [3-(4-isopropylphenyl)-1,1 dimethyl urea] in water has been developed. A derivative of isoproturon [3-(4 isopropylphenyl)-1-carboxypropyl-1-methyl urea] has been synthesized and linked to thyroglobulin using the N-hydrosuccinimide reaction. The immunogen was used to immunize two sheep, which both responded by producing specific antibodies to isoproturon with little cross-reactivity to various structurally related and unrelated pesticides. The enzyme label was prepared by coupling the hapten to horseradish peroxidase using the above reaction. The coated-antibody competitive ELISA, which has a sensitivity of 0.03 microgram l-1, permits the direct determination of isoproturon in various water matrices and can facilitate the monitoring of water quality in drinking-water supplies. PMID- 8192231 TI - Amperometric biosensor for phenols based on a tyrosinase-graphite-epoxy biocomposite. AB - A new biocomposite, based on the incorporation of the enzyme tyrosinase into a graphite-epoxy resin matrix, was used for the effective biosensing of phenolic compounds. The enzyme retains its bioactivity on confinement in the epoxy resin environment. This renewable (polishable) and rigid bioprobe offers convenient quantification for various phenolic substrates. The fast response (steady-state time = 25 s) accrues from the close proximity of the enzyme and graphite sites. The influence of various experimental variables was explored for optimum biosensing performance. Flow-injection monitoring of phenolic compounds at a rate of 50 samples h-1 yielded a detection limit of 1 x 10(-6) mol l-1 and a relative standard deviation of 1.4% (n = 40). PMID- 8192232 TI - Voltammetric determination of dopamine in the presence of ascorbic acid at over oxidized polypyrrole-indigo carmine film-coated electrodes. AB - Over-oxidized polypyrrole films doped with indigo carmine (PPy-IC) offer substantial improvements in voltammetric sensitivity and selectivity towards dopamine. This polymer coating attenuates the voltammetric response of ascorbic acid while the oxidation peak current of dopamine is enhanced by over one order of magnitude compared with that at the bare electrode. The high sensitivity and selectivity for dopamine appears to be mainly due to the charge discrimination and the analyte accumulation. The detection limit is dependent on both film thickness and preconcentration time. At a 0.25 micron thick PPy-IC film-coated electrode, for a 2 min preconcentration time, the detection limit is 10(-8) mol l 1, over two orders of magnitude lower than at a bare glassy carbon electrode. The concomitant ascorbic acid shows no interference although its concentration is as high as 0.1 mmol l-1. The effects of various experimental parameters on the voltammetric response of dopamine were also investigated. The attractive permselective and preconcentrating properties of the PPy-IC films make them valuable for in vivo electrochemistry. PMID- 8192234 TI - The growth of long bones in human embryological and fetal upper limbs and its relationship to other developmental patterns. AB - Measurements were made of the long bones of the upper limbs (humerus, ulna, radius) of 58 aborted embryos and fetuses, developmental age from 8 to 14 weeks, crown-rump length (CRL) between 38 and 116 mm. The specimens were cleared and double-stained, using alcian blue and alizarin red S for a differential detection of cartilage and bone. The values of both the total length (TL) and the ossified part (OL) of each long bone were related to the fetal developmental age previously estimated by freshly measured CRL. The relationship to another developmental pattern, i.e. the number of ossified centres in the vertebral column, suggested that the OL values could be much more significant than TL for the assessment of fetal growth. PMID- 8192233 TI - Hair cell regeneration in the bird cochlea following noise damage or ototoxic drug damage. AB - Hair cells are sensory cells that transduce motion into neural signals. In the cochlea, they are used to detect sound waves in the environment and turn them into auditory signals that can be processed in the brain. Hair cells in the cochlea of birds and mammals were thought to be produced only during embryogenesis and, once made, they were expected to last throughout the lifetime of the animal. Thus, any loss of hair cells due to trauma or disease was thought to lead to permanent impairment of auditory function. Recently, however, studies from a number of laboratories have shown that hair cells in the avian cochlea can be regenerated after acoustic trauma or ototoxic drug damage. This regeneration is accompanied by a repair of the sensory organ and associated tissues and results in a recovery of auditory function. In this review, we examine and compare the structural events that lead to hair cell loss after noise damage and ototoxic drug damage as well as the processes involved in the recovery of the epithelium and the regeneration of the hair cells. Moreover, we examine functional recovery and how it relates to the structural recovery. Finally, we investigate the evidence for the hypothesis that supporting cells in the basilar papilla act as the progenitor cells for the regenerated hair cells and examine the cellular events required to stimulate the progenitor cells to leave the quiescent state, re-enter the cell cycle, and divide. PMID- 8192235 TI - The distribution of GABA-immunoreactive neurons in the brain of the silver eel (Anguilla anguilla L.). AB - The distribution of GABA-immunoreactivity was studied in the brain of the silver eel (Anguilla anguilla) by means of antibodies directed against GABA. Immunoreactive neuronal somata were distributed throughout the brain. Positive perikarya were detected in the internal cellular layer of the olfactory bulb, and in all divisions of the telencephalon, the highest density being observed along the midline. Numerous GABA-reactive cell bodies were found in the diencephalon, particularly in the preoptic and tuberal regions of the hypothalamus, and the dorsolateral, dorsomedial and ventromedial thalamic nuclei. In the optic tectum, the majority of GABA-positive cell bodies were located in the periventricular layer. A number of immunolabeled cell bodies were observed in different tegmental structures, notably the torus semicircularis. In the cerebellum, the Purkinje cells were either very intensely or very weakly immunoreactive. In the rhombencephalon, reactive cell bodies were observed in the eminentia granularis, the valvula cerebellaris, the octavolateral nucleus, the lobus vagus and in the vagal and glossopharyngeal motor nuclei. Intensely immunoreactive axons and terminals were observed in the external granular layer and internal cellular layer of the olfactory bulb. In the telencephalon, the highest density of reactive fibres and boutons was found in the fields of the medial wall. Many immunolabeled fibres were seen in the medial and lateral forebrain bundles. In the diencephalon, intense labelling of fibres and terminals were observed in the nuclei situated close to the midline. In the optic tectum the highest density of reactive fibres was seen in the sfgs, the layer to which the retina projects massively. Finally, in the rhombencephalon the strongest labelling of neurites was observed in the nuclei of the raphe, the nucleus octavocellularis magnocellularis and the nuclei of the IXth and Xth cranial nerves. The GABAergic system of the eel, which is well developed, appears to be generally comparable to that described in tetrapod vertebrates. PMID- 8192236 TI - Calcitonin gene-related peptide-immunoreactivity in functionally identified primary afferent neurones in the rat. AB - In anaesthetized rats, intracellular recordings were made from the somata of lumbar (L4 and L5) dorsal root ganglion cells. The impaled afferent units were first functionally classified by testing the peripheral receptive endings with mechanical stimuli and then iontophoretically injected with a fluorescent dye. Serial sections of the dorsal root ganglion containing the injected soma were incubated with an antibody solution against calcitonin gene-related peptide (CGRP). Somata displaying calcitonin gene-related peptide-immunoreactivity (CGRP IR) possessed receptive endings in the skin and deep somatic tissues (muscle, fascia, tendon, joint). The majority of calcitonin gene-related peptide immunoreactive (CGRP-ir) neurones had conduction velocities below 2.5 m/s; only a few neurones conducted faster than 10 m/s. The immunostained somata were small to medium-sized (cross-sectional area < 1200 microns 2). With one exception, CGRP-IR was found in all types of ending studied, but the proportion of CGRP-ir neurones differed. Immunostained somata were rare among cutaneous and deep low-threshold mechanosensitive units (e.g. hair follicle and muscle spindle units). CGRP-ir somata were most frequent among high-threshold mechanosensitive (presumably nociceptive) afferent neurones (four out of six cells). The data suggest that CGRP can be expressed not only in nociceptive but also in many other types of primary afferent neurone, the condition being that the conduction velocity is slow and/or the cell soma small. PMID- 8192237 TI - Structure and origin of the tooth pedicel (the so-called bone of attachment) and dental-ridge bone in the mandibles of the sea breams Acanthopagrus australis, Pagrus auratus and Rhabdosargus sarba (Sparidae, Perciformes, Teleostei). AB - Scanning electron and light microscopy were used to show that the pedicels of fish teeth (the so-called "bones of attachment") consist of three types of dentine that lie concentrically around a pulp cavity lined with typical odontoblasts with cytoplasmic processes in dentinal tubules. Circumpulpal canalar dentine forms on a thin layer of orthodentine that is encased in mantle dentine. Canalar dentine is a new name given to a dentine that is similar to vasodentine in canal arrangement, but not apparently in canal content. An inner series of wide, radial canals and an outer series of highly-branched thin canals of two diameters are inhabited by a population of cells, the osteodentocytes, and collagen fibril bundles. The flat, oval osteodentocytes appear to be quiescent cells, lying on the sides of the tubules and covered by a sheath. Plump, intensely metachromatic osteodentocytes appear to be more synthetically active. The canals and the osteodentocytes originate from blood capillaries enclosed in the predentine during dentinogenesis. New teeth begin within the small cavities present in spongy bone that were enlarged by multinucleated osteoclasts during tooth growth. Pedicel formation is initiated by the extension of the crown mantle dentine, forming the outer layer of the crimped ligament and outlining the future length and curvature of the pedicel. Central and inner ligament zones are subsequently formed as orthodentine is secreted in both crown and pedicel, and canalar dentine in the pedicel. Spongy bone osteogenesis begins during stage 1 of pedicel formation with the aggregation of osteoblasts and blood capillaries in the bone cavities and in the dermis between the pedicels. Loose fibrillar osteoid condenses into incomplete thin trabeculae bordered by intensely metachromatic osteoblasts. Osteoblasts become enclosed in the developing trabeculae that thicken to give mature spongy bone with osteocytes throughout. We conclude that the pedicels are the true bases of teeth, that the dental ridge is formed from pedicels and spongy bone, and that sea bream spongy bone is cellular. The term "bone of attachment" is inappropriate for the pedicel. It can be used for the spongy bone between the compact bone of the jaw and between adjacent pedicel. PMID- 8192238 TI - Morphological and immunohistochemical differentiation patterns of rabbit uterine epithelium in vitro. AB - We describe morphological and immunohistochemical changes of uterine epithelium from immature rabbits in vitro in response to hormonal treatments, using a matrix coated semipermeable filter. These investigations were compared to in vivo studies of uterine epithelium from immature rabbits treated with estrogen and/or progesterone. In vitro, polarization of the epithelium seems to be best developed under progesterone dominance, and the pattern of cell organelles is similar to those seen in vivo. Two types of apical protrusions could be observed in cultures treated with progesterone, some shaped like domes, containing cell organelles, and some irregular in shape with small lucent vesicles. Both types of apical differentiation are typical for the in vivo situation. In vitro, estrogen leads to a more pseudostratified growth pattern of the cells. They develop apical protrusions with big vesicles probably containing mucin, as in vivo. Treatment with both steroid hormones leads to a heterogeneous response of the uterine epithelial cells in culture, some cells responding more to the estrogen, others to the progesterone whereas in vivo the progesterone-dominant features are obvious. Immunohistochemistry of uteroglobin in monensin-treated cultures gives evidence for uteroglobin secretion in all cultures, but to a lesser extent in the untreated, and this is strongly increased in cultures treated with estrogen and progesterone. These results correspond to observations made in vivo. This in vitro cell culture method seems therefore to provide a useful model for investigating the regulatory mechanisms of sexual steroid hormones and the cell biology of uterine receptivity. PMID- 8192240 TI - Ultrastructural studies and immunolocalization of enamel proteins in rodent secretory stage ameloblasts processed by various cryofixation methods. AB - BACKGROUND: Cryofixation rapidly immobilizes cell and tissue components in their native state, thereby resulting in an ultrastructural preservation very close to the living situation. We have applied this approach to examine the morphology of secretory stage ameloblasts and the distribution of enamel proteins in these cells. METHODS: Molar and incisor tooth germs from newborn mice and/or rats were quickly dissected and divided into segments. The segments were then rapidly frozen using slam, plunge or pressure freezing, freeze-substituted and embedded in Epon. In addition, incisors from older rats were chemically fixed by vascular perfusion and also dehydrated by freeze-substitution. RESULTS: Well-preserved ameloblasts were obtained with all four tissue processing methods. However, slam freezing often showed mechanical damage to the ameloblasts, particularly at the level of the distal portion of Tomes' processes which appeared severed or distorted. Plunging into liquid nitrogen-cooled liquid propane resulted in comparatively less tissue distortion. High pressure freezing gave a relatively higher yield of well-preserved specimens, although displacement of organelles in ameloblasts was sometimes observed, probably resulting from hydrostatic pressure. Minimal ice crystal and mechanical damage was observed in chemically fixed tooth samples processed by freeze-substitution since such specimens are cryoprotected and their examination is not restricted to a surface layer. With all of the above cryopreparation methods, the ultrastructure of well-preserved ameloblasts was, in general, similar to that obtained following conventional chemical fixation, and immunocytochemistry with an anti-amelogenin antibody indicated no profound differences in the distribution of enamel proteins. CONCLUSIONS: These results indicate that, despite some limitations, it is possible to adequately cryofix tooth organs while preserving the architecture of ameloblasts and permitting immunolocalization of enamel proteins. Furthermore, they confirm the general morphology of secretory stage ameloblasts as currently derived from conventional chemical tissue processing. PMID- 8192239 TI - Type II collagen distribution during cranial development in Xenopus laevis. AB - Epithelially expressed type II collagen is thought to play a prominent role in the embryonic patterning and differentiation of the vertebrate skull, primarily on the basis of data derived from amniotes. We describe the spatiotemporal distribution of type II collagen in the embryonic head of the African clawed frog, Xenopus laevis, using whole-mount and serial-section immunohistochemical analysis. We studied embryos spanning Nieuwkoop and Faber (1967) stages 21-39, a period including cranial neural crest cell migration and ending immediately before the onset of neurocranial chondrogenesis. Xenopus displays a transient expression of type II collagen beginning at least as early as stage 21; staining is most intense and widespread at stages 33/34 and 35/36 and subsequently diminishes. Collagen-positive areas include the ventrolateral surface of the brain, sensory vesicles, notochord, oropharynx, and integument. This expression pattern is similar, but not identical, to that reported for the mouse and two bird species (Japanese quail, domestic fowl); thus epithelially expressed type II collagen appears to be a phylogenetically widespread feature of vertebrate cranial development. Consistent with the proposed role of type II collagen in mediating neurocranial differentiation, most collagen-positive areas lie adjacent to subsequent sites of chondrogenesis in the neurocranium but not the visceral skeleton. However, much of the collagen is expressed after the migration of cranial neural crest, including presumptive chondrogenic crest, seemingly too late to pattern the neurocranium by entrapment of these migrating cells. PMID- 8192241 TI - Insertional mutation that causes acrosomal hypo-development: its relationship to sperm head shaping. AB - A family of transgenic mice (OVE 219) was generated by microinjection of a tyrosinase minigene (Ty811C). The transgenic mice demonstrate an atypical and variable coat color pattern and the homozygous males show abnormalities of spermatogenesis that are variably expressed from animal to animal. Heterozygous mice proved to have normal spermatogenesis and along with non-transgenic mice were used as controls to study the abnormalities in spermatogenesis in OVE 219 homozygous males. These abnormalities shed light on the features controlling normal spermatogenesis. In some homozygous males early spermiogenesis was disrupted as the flagellar microtubules became disorganized within the flagellar process. What appeared to be crystalline tubulin was noted within some of the rounded flagellar processes. Sperm with this defect did not develop a flagellum. In other homozygous males defects were apparent by step 6 or 7 of spermiogenesis when the acrosome did not grow and spread over the nucleus as noted in control animals. The modified nuclear envelope underlying the acrosome continued to develop and spread well beyond one margin of the acrosome. Since the modified nuclear envelope grew independently of the acrosome, the acrosome was not the controlling factor in determining the spread of the modified nuclear envelope. Micrographs revealed that Sertoli ectoplasmic specialization failed to form over most regions of the spermatid head lacking a normal acrosome. In homozygous males, the manchette took origin (proximally) in close relation to the modified nuclear envelope and never in relation to the edge of the spreading acrosome, a feature indicating that manchette placement was influenced by the position of the modified nuclear envelope and not the edge of the acrosome. Thus the modification in the nuclear envelope may be the primary event to signal acrosomal spread and manchette development. In spermatids where the manchette developed from an ectopic site, the result was abnormal caudal head shaping. In some spermatids a portion of the manchette was lacking. When this occurred the caudal head was rounded in the region of the missing manchette. In a minority of spermatids there was no evidence for a manchette. The entire caudal head was gently rounded. These data support the growing body of evidence that the caudal sperm head is shaped, in part, by the manchette. The OVE 219 family of mice provides a useful model to understand the processes involved in periods of spermiogenesis that are critical to development of a normally shaped sperm head. PMID- 8192242 TI - Pulmonary hypoplasia associated with reduced thoracic space in mice with disproportionate micromelia (DMM). AB - BACKGROUND: Fetal mice homozygous for the Disproportionate micromelia (Dmm) gene were studied as a model for pulmonary hypoplasia in chondrodystrophy. METHODS: Wet weight, dry weight, and biochemical content were determined in excised whole lungs, terminal sac morphology and presence of multilamellar bodies were determined by electron microscopy, and volume of the thoracic space was estimated from paraffin casts. Lung development of the mutant was further assessed in whole organ culture. RESULTS. Compared with normal littermates, the mutant showed a significant decrease (28%) in lung wet weight without showing altered lung dry weight or tissue content of DNA and protein. The terminal sacs of lungs fixed by intratracheal instillation were significantly smaller than normal. However, the lungs appeared to have undergone maturation on schedule since the surfactant precursors, multilamellar bodies, were observed and normal tissue-levels of phospholipid were detected. The volume of the mutant's thorax was markedly reduced. Finally, the mutant's lungs when removed from the fetus prior to the onset of thoracic dystrophy (day 15) and cultured for three days demonstrated that, without the confining influence of a reduced thoracic space, they are capable of development comparable to normal. CONCLUSIONS: These findings support the hypothesis that the Dmm mutant can be further studied as a model for human pulmonary hypoplasia associated with chondrodystrophy, and that the relationship between the reduced thorax and the lung disorder is cause-and-effect. PMID- 8192243 TI - Organization of tracheal epithelium in the cartilaginous portion of adult rabbit and its persistence in organ culture. AB - BACKGROUND: The rabbit trachea provides a model system to test the physiological responses of the airways to various agents. Since three-dimensional organization may affect responses of an organ, an organ culture model was established in serum free medium. METHODS: Tracheas were fixed in situ, at steps in the preparation of organ cultures, and after one day to three weeks in organ culture. Samples were examined by light microscopy and scanning and transmission electron microscopy for surface morphology, distribution of cell types, and characteristics of the epithelial cell layer. RESULTS: The normal tracheal mucosa was discovered to consist of extensive circumferential folds in the cartilaginous portion, which were enhanced upon isolation of the trachea from the animal. The folds consisted principally of differences in epithelial cell height rather than folding of the lamina propria. Enhancement of folding upon removal of the trachea coincided with increased secretion by Clara and possibly mucous cells. In organ culture, epithelial cell height initially increased, producing tall folds and cell types were retained in normal proportions. After prolonged culture, cilia were lost but glandular secretion continued. CONCLUSIONS: Changes in the arrangement of basal cells and secretory activity in isolated trachea and in culture may give insight into the functional significance of the epithelial folds. PMID- 8192244 TI - Development of the high endothelial venule in rat lymph node autografts. AB - Vascular reconstruction during rat lymph node regeneration was investigated in autotransplanted mesenteric lymph node fragments, which had been implanted in the renal parenchyma. In addition to light microscopy, vascular casting and transmission electron microscopy were used. From day 3 onwards capillaries grew into the autografts together with lymphatic vessels. The capillaries showed obvious signs of proliferation by day 5. The surviving interstitial cells at the outer border of the transplant produced extracellular substance. High endothelial venules (HEV) differentiated from capillaries from about day 7. A first sign of their development was a vessel with a narrow, branching luminal space and with endothelial cells containing rich cytoplasm and small Golgi complexes. As the Golgi complexes grew and the cisternae and vesicles increased, the lumen dilated, the cell coat on the luminal surface became prominent, and, finally, lymphocytes emigrated through these venules from around day 10. The typical lymph node structure was complete by day 28. These results suggest that the interaction among the remaining interstitial cells, invading capillaries, and lymphatic penetration results in differentiation and maturation of HEV in lymph node regeneration. The development of Golgi complexes is strongly associated with lymphocyte emigration from the blood. PMID- 8192245 TI - Expression patterns of ammonia-metabolizing enzymes in the liver, mesonephros, and gut of human embryos and their possible implications. AB - Human and ungulate embryos can catabolize amino acids for energy production, whereas rodent embryos cannot, raising the question whether studies of rodent model systems are suitable for extrapolation to the human situation. Therefore, we investigated the expression of the amino acid- and ammonia-metabolizing enzymes glutaminase, glutamate dehydrogenase, glutamine synthase, carbamoylphosphate synthase, and arginase immunohistochemically in a graded series of human embryos and fetuses. During human development the expression of these enzymes is first seen in the liver, then in the mesonephric kidney, and finally in the small intestine. Such a simultaneous expression of nitrogen metabolizing enzymes was not seen in any other organ. The early appearance of the enzymes involved in amino acid and ammonia metabolism in the human liver, compared to, for example, the rat liver, suggests that catabolism of amino acids may provide an important supply of metabolic energy for the human embryo. The coexpression of glutaminase, glutamate dehydrogenase, and carbamoylphosphate synthase, but not of arginase, in the mesonephros and the small intestine suggests that these organs are involved in the biosynthesis of intermediates of the ornithine cycle, e.g., arginine or citrulline. From a comparison of the developmental appearance of ornithine cycle enzymes in different mammalian species we postulate that an early appearance of these enzymes is generally associated with a relatively slow prenatal growth rate and the use of amino acids as metabolic fuel. PMID- 8192246 TI - Meckel's cartilage in the human embryo and fetus. AB - This work studied the development of the ventral part of Meckel's cartilage in a series of human embryos (classified in stages) and fetuses. These stages appeared particularly important: stage 16, appearance of Meckel's cartilage; stage 20, beginning of membranous ossification of mandible; and stage 23, end of the embryonic period (8th week). The primitive bony nodule which develops from the embryonic mesenchyme appears as a double bony layer forming a groove containing the neurovascular bundle, into which the dental lamina is also invaginated. It was concluded that during the fetal period, the cartilage participates in the formation of the body of the mandible in an area close to the mental foramen via endochondral ossification. The cartilage disappears in parallel with the development of ossification by the sixth month. PMID- 8192247 TI - Ultrastructure and development of a thick basement membrane-like layer in the anchoring villi of macaque placentas. AB - BACKGROUND: Anchoring villi and cytotrophoblastic cell columns are important structural components involved in placental morphogenesis. We have previously described the presence of an unusual basement membrane-like layer (BMLL) that separates these placental compartments. The purpose of the present study was to identify developmental changes in the ultrastructure of the BMLL and to assess its changes in extracellular matrix composition over the course of gestation. METHODS: Conventional techniques were used to examine macaque placental tissue by transmission electron microscopy. Standard immunoperoxidase methods were used to identify type IV collagen, laminin and fibronectin in paraffin sections. RESULTS: Until day 35 of gestation the BMLL was 70-100 nm thick and appeared similar to basement membranes seen in other regions of the villus, although it usually lacked a lamina lucida along the surface adjacent to the cytotrophoblast cells. Immunohistochemistry revealed the presence of laminin and type IV collagen in the BMLL. By 53 days of gestation the BMLL had hypertrophied at the junction of the anchoring villus and cell column, measuring 2,000-5,000 nm in thickness. The BMLL retained immunoreactivity for laminin and type IV collagen. Ultrastructural examination revealed the presence of a new component in the form of 10 nm microfibrils. By 89 days of gestation the BMLL was not reactive for laminin or type IV collagen but otherwise maintained the structural organization seen at 53 days. No additional changes were observed in the BMLL during late pregnancy. CONCLUSIONS: The BMLL is a distinct extracellular matrix region that separates the distal aspect of the anchoring villus from the proximal portion of the cell columns. Evidence indicates that adjacent cytotrophoblast plays a prominent role in the production of the BMLL. The BMLL may serve to organize this complex tissue by separating fetal mesenchyme from cytotrophoblast cells that are proliferating, differentiating, and migrating. Modifications to the composition of the BMLL may indicate changes in the role this matrix plays in the development of the placenta. PMID- 8192248 TI - Quantitative study of the apical nerve fibers of adult and juvenile rat molars. AB - The rat molar has become an important model for studies of interactions between nerves and the pulp-dentin complex, yet there is only limited quantitative information on the number and size distribution of axons entering the roots of this tooth. This study was undertaken to provide such a detailed characterization of the apical innervation of the rat molar. An additional objective was to compare the apical nerve composition of young, recently erupted rat molars with that of mature teeth in order to determine whether there is ongoing maturation of the innervation after the teeth have attained functional occlusion. A complete census was made of the nerve fibers entering the roots of both mature and recently erupted juvenile mandibular first molars in Sprague-Dawley rats. Each of the four roots of the first molars was processed for electron microscopy of thin sections near the apex. The majority of intradental nerve fibers entered the molar via the two larger (mesial and distal) roots. Within the apical root pulp, most, but not all, axons occurred within well-defined fascicles associated with blood vessels. Molars from adult animals (age 4 months) had a mean total of 232 (S.D. = 49, N = 7 teeth) myelinated fibers and 806 (S.D. = 143) unmyelinated axons entering the four roots. Fibers exceeding the A delta size range (circumference > or = 19 microns) accounted for only 4% of the myelinated axons at the apex. Molars from juvenile animals (age 4 weeks) had fewer myelinated fibers (mean 176, S.D. 18, N = 8), but more unmyelinated axons (mean 1,174, S.D. 160) than adults. The mean ratio of unmyelinated axons to myelinated axons was 6.6:1 for juveniles compared to 3.5:1 for adults. Juvenile teeth contained no myelinated fibers that exceeded 19 microns in circumference. These results indicate that the innervation of the rat molar resembles that of teeth of non rodent mammals in that (1) innervation density is high, (2) there is a high ratio of unmyelinated axons, and (3) most of the myelinated fibers are of thin caliber. Furthermore, it appears that after the molar erupts, maturation of the nerve fiber composition continues with processes that include both a marked decrease in the number of unmyelinated axons and an increase in the number and size heterogeneity of myelinated fibers. PMID- 8192249 TI - Fine structure of taste buds located on the lamb epiglottis. AB - BACKGROUND: Taste buds located on the aryepiglottal folds and laryngeal surface of the epiglottis are the principal receptors responsible for the initiation of the laryngeal chemoreflex. In contrast to the wealth of information available concerning the ultrastructure of oral taste buds, little comparable data exists for taste buds located at the entrance to the larynx. Therefore, the present study was designed to investigate the fine structure of taste buds located on the lamb epiglottis. MATERIALS: Stained thick and semi-serial thin sections from taste buds located on the lamb epiglottis were examined with light and electron microscopy. RESULTS: Based on morphological criteria, three types of cells could be identified in the taste bud: Type I, Type II, and basal cells. Both Type I and Type II cells extended into the apical taste pore, but there were differences between these two cell types with regard to nuclear profiles, electron density, and the relative density of ribosomes, apical mitochondria, and rough and smooth endoplasmic reticulum. Basal cells did not extend a process into the taste pore. Nerve processes were observed throughout the taste bud. Synapses were observed between both Type I and Type II cells and nerve fibers. These synapses exhibited membrane thickenings and accumulations of clear and dense-cored vesicles of varying proportions in the taste cell cytoplasm adjacent to membrane specializations. CONCLUSIONS: The taste buds located on the lamb epiglottis share several structural similarities to taste buds located in the oral cavity and other regions of the pharynx and larynx of many mammalian species. The presence of synapses on both Type I and Type II cells of the lamb epiglottal taste bud suggests that both cell types are involved in laryngeal chemoreception. PMID- 8192250 TI - Posterior right diagonal artery. AB - BACKGROUND: There is general confusion about a branch of the posterior segment of the right coronary artery that has been referred to as 1) the lower trunk of a divided right coronary artery; 2) a posterior reflection of the right marginal artery; 3) the ramus lateralis; and 4) a posterolateral branch or a posterior descending artery. MATERIALS: Three hundred human hearts were studied by direct observation, X-ray films, and corrosion casting. RESULTS: This branch of the right coronary artery arises either after the right marginal artery (in 84% of hearts) or it constitutes the continuation of this artery in the remaining 16%. We named it the posterior right diagonal artery (PRDA). It was found in 14% of 266 hearts of right dominant type. It was present in 39% when the length of the posterior descending artery (PDA) was shorter than half of the length of the posterior interventricular sulcus (PIS) and in 6% when it was longer. When the PRDA originated directly from the RCA, the RMA appeared underdeveloped; the PRDA always occupied the inferior part of the PIS and appears either as continuation of a short PDA or as a replacement for a long PDA from the point where this artery leaves the PIS to enter the posterior wall of the left ventricle. The PDRA when present serves as a bridge between the RCA and the left anterior descending artery. CONCLUSIONS: These findings are of practical importance for the correct interpretation of coronary arteriographies and in the field of coronary artery surgery. PMID- 8192251 TI - [Bibliography of Scientific Records of the Pomeranian Academy of Medicine in Stetin from the years 1974-1978]. PMID- 8192252 TI - Blood cell deformability in horses with intestinal colic. AB - Hematologic and rheologic variables were examined in a group of 13 horses with intestinal colic and a control group of 6 horses. All horses had been recently transported to the veterinary teaching hospital, and blood samples were obtained during initial examination. There were no significant differences in blood neutrophil count or plasma fibrinogen concentration between the groups, and PCV was significantly increased in horses with intestinal colic. Cell filterability was measured by passing uniform concentrations of blood, erythrocytes, and neutrophils through micropore filters. There were no significant differences between the control and intestinal colic groups in filterability of erythrocytes. Significant (P < 0.05) prolongation in filterability of blood and neutrophils was observed in the group of horses with intestinal colic, compared with the control group. This neutrophil change, indicative of decreased neutrophil deformability, corresponded with severity of the illness. Horses that failed to survive the intestinal colic episode had significantly (P < 0.05) prolonged blood and neutrophil filterability, compared with horses that survived intestinal colic. These findings indicate that deformability of neutrophils decreases in horses with intestinal colic, possibly a result of endotoxin-induced activation. This change can further impede microvascular blood flow that is altered in association with intestinal ischemia. PMID- 8192253 TI - Ultrasonography of the reticulum in cows. AB - The reticulum and adjacent organs were examined ultrasonographically in 51 cows by use of a 3.5-MHz linear transducer applied to the ventral aspect of the thorax over the sixth and seventh intercostal spaces. Examination included assessment of the contour of the reticulum, of reticular contractions, and of the organs adjacent to the reticulum. The normal reticulum appeared as a half-moon-shaped structure with a smooth contour; it contracted at regular intervals and was situated immediately adjacent to the diaphragm and ventral portion of the abdominal wall when relaxed. Contents of the reticulum could not normally be imaged because of its partly gaseous composition. The ruminoreticular groove, craniodorsal blind sac of the rumen, and the ventral sac of the rumen were observed caudally. The distal aspect of the spleen and parts of the omasum, abomasum, and liver could be imaged. Reticular motility was characterized by a biphasic contraction pattern. Four biphasic reticular contractions usually were observed during a 4-minute period. During the first (incomplete) contraction, the reticulum contracted by a mean of 7.2 +/- 2.30 cm. There was then low-grade, incomplete relaxation of the reticulum, followed immediately by the second reticular contraction, during which the reticulum usually disappeared from the 17.5-cm-deep screen. The reticulum then reappeared in its normal position. The first reticular contraction lasted a mean of 2.6 +/- 0.33 seconds and the second contraction lasted 3.9 +/- 0.55 seconds. The mean interval between 2 biphasic contractions was 44.9 +/- 10.53 seconds. The speed of the first reticular contraction was 5.4 +/- 1.32 cm/s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192254 TI - Resistance of Chinese Meishan, Fengjing, and Minzhu pigs to the K88ac+ strain of Escherichia coli. AB - The microscopic brush border membrane adherence assay was used to determine resistance (nonadherence) and susceptibility (adherence) of Chinese pigs (n = 289) to the K88ac+ strain of Escherichia coli-mediated disease. This study estimates prevalence of resistance to diarrheal disease in multiple family lines (no common ancestry for a minimum of 3 generations) for the Chinese Meishan, Fengjing, and Minzhu breeds. Results of in vitro assays indicate that pigs of the Meishan breed are highly resistant (nonadherent) to K88ac+ E coli-mediated disease. The gene conferring susceptibility to K88ac+ E coli-mediated disease exists at low frequency in pigs of the Minzhu breed. Minzhu-type (crossbred) pigs of both phenotypes (susceptible and resistant) were identified in ratios consistent with a 1-locus gene model. Given that all susceptible pigs were from 1 site, frequency of susceptibility within this Minzhu population is estimated at 8%. Inheritance within the Fengjing breed is still unclear because a weakly adherent phenotype, as well as the resistant phenotype, was identified. The weakly adherent phenotype was observed in pigs derived from multiple family lines. Expression of the weakly adherent phenotype in terms of susceptibility to disease is not known at this time. PMID- 8192255 TI - Use of polymerase chain reaction to detect porcine parvovirus associated with swine embryos. AB - The role of porcine parvovirus (PPV) in inducing reproductive failure in swine has been extensively documented. However, information is not available as to the risk of PPV transmission by embryo transfer. Using the polymerase chain reaction (PCR) technique, PPV-specific DNA was detected in association with 4-day-old porcine embryos incubated in vitro in the presence of NADL-8 strain of PPV, despite attempts to rid the embryos of virus by either washing or treatment with pronase or trypsin. The presence of PPV in embryos collected from acutely infected swine was not detected by PCR, although PPV DNA was detected in the proximal portion of the reproductive tract during the early stages of infection. Viral-specific nucleic acid was not detected in embryos transferred from infected donors to seronegative recipients and retrieved and assayed on the 15th and 32nd days of gestation. Results of the use of PCR to detect PPV associated with swine female reproductive tract and embryos ascribe minimal risk to the transmission of PPV to seronegative recipients through embryo transfer. PMID- 8192256 TI - Antigenic composition of Pasteurella haemolytica serotype-1 supernatants from supplemented and nonsupplemented media. AB - Supernatant preparations containing antigens produced by Pasteurella haemolytica serotype 1 grown in nonsupplemented RPMI 1640 medium and 3 grown in supplemented RPMI 1640 media were evaluated. Antigens were detected by immunoblotting each supernatant preparation with sera from 20 cattle with various degrees of resistance to experimentally induced pneumonic pasteurellosis. Antigen-antibody bands at 49 and 30 kd were correlated with resistance in all 4 media. A 66-kd antigen-antibody band was correlated with resistance in 2 media, and antigen antibody bands at 100 and 16 kd were correlated with resistance in 1 medium each. These results indicated that the number and relative amount of resistance associated antigens in P haemolytica supernatants can be optimized on the basis of type of growth medium used. PMID- 8192257 TI - Efficacy of injectable abamectin against gastrointestinal tract nematodes and lungworms of cattle. AB - Efficacy of abamectin against gastrointestinal tract nematodes and lungworms of cattle was determined in 4 experiments. The first 2 experiments were controlled trials in which efficacy was determined at necropsy in calves with either experimentally induced (n = 14) or naturally acquired (n = 16) infections. Half the calves in each experiment were treated with abamectin (200 micrograms/kg of body weight, SC), and half were left untreated as controls. Efficacy was > 99% against adult stages of Dictyocaulus viviparus, Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Cooperia punctata, Trichuris discolor, and C oncophora, and was 92.4% against Nematodirus helvetianus. The second 2 experiments were clinical trials in which efficacy was determined by fecal egg count reduction in naturally infected yearling heifers (n = 75) or 2-year-old heifers (n = 75). Within replicates of 5, 4 heifers were assigned at random to treatment with 200 micrograms of abamectin/kg and 1 was left untreated as a control. Abamectin was 100% effective in eliminating strongylate nematode eggs from the feces of these heifers. In all experiments, adverse reactions were limited to small, clinically unimportant injection site swellings in 29% of abamectin-treated calves. Abamectin was judged to be safe and effective in these trials. PMID- 8192258 TI - Pharmacokinetics and tissue residues of spiramycin in cattle after intramuscular administration of multiple doses. AB - Pharmacokinetic variables of spiramycin and its distribution in muscle, liver, kidney, and injection sites were studied in 18 mixed-sex 1-year-old calves to assess drug withdrawal time after 2 IM administrations of 100,000 IU of spiramycin/kg of body weight at 48-hour intervals. Presence of a compound, other than spiramycin I (ie, neospiramycin), was observed in tissues used for withdrawal time determination. High concentrations observed at the injection sites decreased slowly to maximal residue limit with half-life of 109.5 hours for neospiramycin and 77.5 hours for spiramycin. At 14 days, neospiramycin concentrations were higher in kidney than in liver and half-life was different between these 2 tissues. Two methods of withdrawal time determination were used and the part of the samples without residue detected, in the calculation, was discussed. Withdrawal time of 35 days can be proposed on the basis of average daily intake determined for spiramycin, with concentration at injection sites representing 10% of the whole muscle concentration. PMID- 8192260 TI - Repeatability and normal values for measurement of pharyngeal and tracheal pressures in exercising horses. AB - Repeatability of measurements of peak and mean tracheal and pharyngeal pressures in exercising horses was determined. Five athletically fit horses were subjected to repeated (n = 5) standardized exercise trials. Static pressures in the trachea, nasopharynx, and mask were determined. At least 96% of all mean pressure measurements were within 5 cm of H2O of the mean value for any horse. Peak pressure measurements were less repeatable, but at least 96% of all measurements were within 10 cm of H2O of the mean peak measurements for any horse. In 10 horses galloping at 14 m/s, the 95% confidence interval for peak tracheal and pharyngeal inspiratory pressures ranged from -40 to -50 cm of H2O and -20 to -26 cm of H2O, respectively. During expiration, the 95% confidence interval for peak tracheal and pharyngeal pressure at the same speed ranged from 15 to 28 cm of H2O and 10 to 24 cm of H2O respectively. During inspiration, horses with induced laryngeal hemiplegia had static pressure measurements generally outside that range. We conclude that determination of tracheal and pharyngeal pressures is a potentially useful adjunct for assessment of the proximal portion of the respiratory tract. PMID- 8192259 TI - Hemodynamic and analgesic effects of propofol infusion in medetomidine premedicated dogs. AB - Hemodynamic and analgesic effects of medetomidine (30 micrograms/kg of body weight, IM), atropine (0.044 mg/kg, IM), and propofol (2 mg/kg, IV, as a bolus, and 165 micrograms/kg/min, IV, for 60 minutes, as an infusion) were evaluated in 6 healthy adult Beagles. Catheters were placed while the dogs were anesthetized with isoflurane in oxygen. Administration of isoflurane was then discontinued, and dogs were allowed to breath oxygen until end-tidal isoflurane concentration was < or = 0.5%. At this time, baseline measurements were recorded and medetomidine and atropine were administered. Ten minutes later, the bolus of propofol was given and the infusion was begun. Analgesia was evaluated with a tail clamp test and by use of a direct-current nerve stimulator. Sinoatrial and atrioventricular blockade developed in all 6 dogs within 2 minutes of administration of medetomidine and atropine, but disappeared within 10 minutes. Apnea did not develop after administration of propofol. Analgesia was strong and consistent throughout the entire 60-minute period of propofol infusion. Medetomidine significantly (P < 0.05) increased systemic vascular resistance and decreased cardiac output, compared with baseline values. Propofol infusion appeared to alleviate medetomidine-induced vasoconstriction. Recovery was smooth and uncomplicated. All dogs were able to walk normally at a mean time (+/- SEM) of 88.2 +/- 20.6 minutes after termination of propofol infusion. It was concluded that medetomidine, atropine, and propofol, as given in the present study, is a safe combination of anesthetic drugs for use in healthy Beagles. PMID- 8192261 TI - Effects of acetylpromazine, xylazine, and vertical load on digital arterial blood flow in horses. AB - Palmar digital arterial blood flow was measured in 6 conscious, standing horses, using surgically placed perivascular ultrasonic flow probes. The effects of 2 dosages of xylazine (0.55 and 1.1 mg/kg of body weight) and of 3 dosages of acetylpromazine (0.01, 0.02, and 0.04 mg/kg), as well as the effect of vertical load, on digital blood flow were evaluated. Intravenous administration of xylazine induced a significant (P < 0.05), transient decrease in digital blood flow. Intravenous administration of acetylpromazine induced a significant (P < 0.05), prolonged increase in digital blood flow. Correlation between vertical load and digital blood flow was found. The results of this study indicate that use of acetylpromazine may be beneficial in clinical treatment of horses with reduced digital blood flow. Xylazine, on the other hand, may exacerbate ischemic conditions of the digit and should be used with caution. PMID- 8192262 TI - Early insulin response to an intravenous glucose tolerance test in horses. AB - Plasma insulin concentration of many species has a characteristic early or acute phase response in the minutes after IV administration of glucose. However, the plasma insulin response of horses soon after the IV administration of glucose has not been examined, whereas the more prolonged response has been evaluated. We examined the plasma insulin and glucose concentration responses of adult mares during the 30 minutes after rapid IV administration of glucose (0.33 g/kg of body weight). Plasma glucose concentration peaked at 664 +/- 54 mg/dl within 1 minute of cessation of glucose administration, whereas insulin concentration peaked at 326 +/- 24 pmol/L at 2 minutes after the end of glucose administration. Thus, these mares had an acute insulin response, consistent with that observed in other species, including dogs, human beings, and cattle. PMID- 8192263 TI - Pulmonary intravascular macrophages in horses and ponies. AB - Seven horses (4 anesthetized and 3 awake) and 2 ponies (anesthetized) were studied to evaluate the high sensitivity of the pulmonary circulation of the horse to various blood-borne particles, and to establish the presence of intravascular macrophages in the lung. Pulmonary and systemic pressures and cardiac output before and during particle injection were measured in some animals. An anesthetized foal had a large increase in pulmonary arterial pressure (32 and 34 mm of Hg) within 1 minute of IV administration of small test doses of radioactively labeled liposomes (2.5 mumol/kg of body weight) or a 1% suspension of blue pigment (0.3 ml/kg), respectively. Quantitative real-time gamma camera imaging of the foal revealed high retention of the labeled liposomes during the first pass through the lungs; retention persisted throughout the experiment. Postmortem analysis revealed 55 and 47% lung retention of liposomes and blue pigment, respectively. The 2 anesthetized ponies had increased pulmonary artery pressure of 34 +/- 7 mm of Hg, decreased cardiac output, and 42% lung retention after administration of 1% blue pigment (0.2 ml/kg), whereas 3 awake horses had increased pressure of 28 +/- 9 mm of Hg after 1.8 x 10(8) (1.8-microns-diameter) latex microspheres/kg. None of the injected particles caused vascular obstruction, and they do not cause pulmonary vascular reactivity in species that lack pulmonary intravascular macrophages. Finally, 3 horses (1 anesthetized and 2 awake) were infused IV with small doses of the blue pigment, and their lungs were perfusion-fixed to identify specific labeling of the pulmonary intravascular macrophages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192264 TI - Alterations in blood viscosity in horses competing in cross country jumping. AB - Packed cell volume and plasma total protein (TP), serum albumin (Alb) and globulin (Glb), and plasma ionized calcium (PCa) concentrations, blood viscosity (BV), and plasma viscosity (PV) were measured in 42 horses at rest and after the cross country jumping phase of a horse trial competition. The BV and PV were determined at 6 shear rates (230, 115, 46, 23, 11.5, 5.75 s-1), using a digital rotational cone and plate microviscometer. A paired t-test was used to determine differences between PCV, TP, Alb, Glb and PCa values at rest and after exercise. The PCV, TP, Alb, and Glb values increased (P < 0.05) in horses after exercise. The PCa concentration decreased (P < 0.05) in horses after exercise. Mean BV and PV in the 42 horses at rest and after exercise were fitted to an asymptotic function. Significant (P < 0.05) correlation at all shear rates was seen between BV at rest and PCV, TP, Alb, Glb, and PCa values at rest; and between BV after exercise and PCV, TP, Alb, Glb, and PCa values after exercise. Significant correlation was not seen between PV at rest and TP, Alb, Glb, and PCa at rest, or between PV after exercise and TP, Alb, Glb, and PCa concentrations after exercise at any shear rate. PMID- 8192265 TI - Effects of low and high fractions of inspired oxygen on ventilation in ducks anesthetized with isoflurane. AB - High fractions of inspired oxygen are commonly used during general anesthesia in birds. Observations in ducks anesthetized with halothane or pentobarbital indicated that high fractions of inspired oxygen depress ventilation. The purpose of this study was to test the hypothesis that ducks hypoventilate when breathing high fractions of inspired oxygen, compared with the same ducks breathing low fractions of inspired oxygen. Respiratory variables were recorded in 7 ducks anesthetized with 1.4% isoflurane in oxygen. Four concentrations of oxygen (21, 40, 70, and > 90%) were used for each duck. Respiratory rate decreased as the fraction of inspired oxygen increased, but not significantly. There was a significant decrease in tidal volume as PaCO2 increased. Hyperoxia was observed to contribute to hypoventilation in ducks anesthetized with isoflurane in oxygen. PMID- 8192266 TI - Development of an experimental model of hypothyroidism in cockatiels (Nymphicus hollandicus). AB - Hypothyroidism is a possible predisposing factor in a number of disorders of companion psittacine birds. We developed and validated a thyroid-stimulating hormone (TSH) response testing protocol for cockatiels (Nymphicus hollandicus), using 0.1 IU of TSH/bird given IM, with blood sample collection at 0 and 6 hours after TSH, and a commercial radioimmunoassay for thyroxine (T4). This protocol was used to document a seasonal sex difference in stimulated T4 values--females responded with higher T4 values than those in males in summer--and a stress induced depression of baseline T4 values was detected in a group of cockatiels with normal TSH response. An experimental model for mature-onset hypothyroidism in cockatiels was created by radiothyroidectomizing cockatiels with 3.7 MBq (100 microCi) of 131I/bird given IV. Induction of the hypothyroid state was confirmed by baseline T4 concentration, TSH response test results, thyroid pertechnetate scintigraphy, and gross and microscopic examinations. Classical signs of hypothyroidism (eg, hypercholesterolemia, obesity, poor feathering) were lacking or mild at 48 days after thyroid ablation. PMID- 8192267 TI - Quantitative comparison of the stress response of striped bass (Morone saxatilis) and hybrid striped bass (Morone saxatilis x Morone chrysops and Morone saxatilis x Morone americana). AB - Striped bass (Morone saxatilis) exposed to a standardized confinement stress had markedly different clinical and endocrinologic responses, compared with hybrid striped bass exposed to the same stress. Plasma cortisol concentration increased at a faster rate and appeared to reach a higher value in striped bass than in hybrid bass. Mean plasma cortisol concentration was 742 +/- 43 ng/ml in striped bass, compared with 490 +/- 37 and 531 +/- 40 ng/ml in striped bass x white perch (M americana) and striped bass x white bass (M chrysops) hybrids, respectively, after a 45-minute net confinement. Plasma cortisol concentration also remained significantly (P = 0.003) higher in striped bass for at least 48 hours after the net confinement. These hormonal differences were associated with a markedly lower survival and resistance to infection in striped bass, compared with the hybrids. PMID- 8192268 TI - Phenotype and biological activity of neonatal equine chondrocytes cultured in a three-dimensional fibrin matrix. AB - Equine neonatal chondrocytes were cultured in three-dimensional fibrin matrices under conditions of immediate implantation or implantation following monolayer culture for 6 days, and 3 cell concentrations (1 x 10(5), 1 x 10(6), and 5 x 10(6) chondrocytes/cm3). Equine fibrinogen was collected by cryoprecipitation and polymerized by use of activated bovine thrombin. The fibrin implants were harvested and analyzed histologically and biochemically at 3, 7, and 14 days after the chondrocytes were implanted in fibrin. The differentiation ratio (ratio of rounded, chondrocyte-like cells to stellate, fibroblast-like cells) was statistically higher for implants that received 5 x 10(6) precultured cells at all time periods than for implants that received 1 x 10(5) or 1 x 10(6) precultured cells. The differentiation ratio was statistically higher for implants that received 5 x 10(6) immediately implanted cells than for other implants at 7 days after implantation. At 14 days, implants that received 5 x 10(6) precultured chondrocytes had a higher differentiation ratio than did implants that received 5 x 10(6) chondrocytes that had not been precultured. Among implants that received precultured chondrocytes, total glycosaminoglycan and chondroitin sulfate content was lowest for implants that received only 1 x 10(5) cells. Among implants that received chondrocytes that had not been precultured, glycosaminoglycan content was not significantly different among the 3 cell concentrations, and chondroitin sulfate content was different only between implants that received 5 x 10(6) vs 1 x 10(6) cells. Only after the longest incubation period and at the highest cell concentration studied did preculturing of chondrocytes improve maintenance of phenotype. Preculturing did not appear to influence proteoglycan synthesis. PMID- 8192269 TI - Holding power of orthopedic screws in the large metacarpal and metatarsal bones of calves. AB - Holding power was determined for various orthopedic screws in bones of calves. Holding power was defined as maximal tensile force required to remove a screw divided by thickness of bone engaged by the screw (kN/mm). Comparative pull-out tests were performed, using pairs of large metacarpal or metatarsal bones from calves aged 3 to 14 days. Comparisons were made of the holding power of 6.5-mm fully threaded cancellous screws and 5.5-mm cortical screws in the proximal and distal metaphyses, and of 4.5-mm and 5.5-mm cortical screws in the diaphysis. Sixteen repetitions of each comparative trial were performed. There was no statistically significant difference in the holding power of 4.5- and 5.5-mm cortical screws in the diaphysis. There was no significant difference in the holding power of 5.5-mm cortical and 6.5-mm fully threaded cancellous screws in the proximal metaphysis. In the distal metaphysis, 6.5-mm fully threaded cancellous screws had significantly (P < 0.001) greater holding power than did 5.5-mm cortical screws. There was no significant difference between the mean holding power of 5.5-mm cortical screws in the proximal metaphysis and 5.5-mm cortical screws in the distal metaphysis. There was significantly (P < 0.01) greater mean holding power of 6.5-mm cortical, fully threaded cancellous screws in the distal metaphysis, compared with the proximal metaphysis. PMID- 8192270 TI - Antibody binding of circulating ergot alkaloids in cattle grazing tall fescue. AB - Direct evidence linking alkaloids found in endophyte-infected tall fescue forage with the livestock disorder known as fescue toxicosis is lacking. Physiologic effects of fescue toxicosis include reduced serum prolactin concentration in cattle. A monoclonal antibody specific to the lysergic moiety of ergot alkaloids was developed in mice after creating an immunogen by linking lysergol to human serum albumin. The antibody was specific to the lysergic moiety and, therefore, it cross-reacted with ergot alkaloids, lysergic acid, and lysergol. The antibody did not cross-react with alkaloid derivatives that had bromated or hydrogenated lysergic ring moieties. Fescue toxicosis conditions were elicited in yearling Angus steers by permitting them to graze endophyte-infected tall fescue containing > 650 micrograms/kg of ergovaline for 60 days. Passive immunization of steers by infusion of the monoclonal antibody increased serum prolactin concentration by 7 ng/ml, beginning immediately after infusion. Control steers did not respond to treatment with bovine serum albumin. Active immunization of yearling Angus heifers with immunogens containing lysergol or ergonovine linked to human serum albumin resulted in an antibody response. PMID- 8192271 TI - Structure of equine type I and type II collagens. AB - Collagen type I was purified from equine skin and flexor tendon, and type II collagen was purified from equine articular cartilage. The proteoglycans in these tissues were extracted, using guanidine HCl; the collagens were solubilized, using pepsin digestion, then were selectively precipitated with NaCl. Gel electrophoresis indicated that the precipitates contained only type I or type II collagen. Amino acid analysis indicated that collagen constituted > 97% of the total protein in the precipitates. Hydroxylation of proline was 42.0 +/- 0.6% (mean +/- SEM) in alpha 1(I) and alpha 2(I), and was 48.1 +/- 1.3% in alpha 1(II) chains. The hydroxylation of lysine was 23.2 +/- 0.7% in alpha 1(I) and 34.1 +/- 0.9% in alpha 2(I) chains from tendon, and 49.6 +/- 4.3% in alpha 1(II) chains from cartilage. The cyanogen bromide (CB)-peptide patterns of chromatographically purified equine alpha 2(I) and alpha 1(II) chains were similar to those published previously for rat, bovine, and human alpha 2 and alpha 1 chains. However, the CB peptide pattern of the equine alpha 1(I) chain resembled the guinea pig alpha 1(I) chain, which has no methionine between CB7 and CB6. Purified equine alpha 1(I)CB7,6 contained no methionine, methionine sulfoxide, or homoserine lactone. Mass of 42.26 kd was determined by use of mass spectrometry, and N-terminal sequence analysis established that the first 12 amino acids of this CB7,6 were identical to the sequence of human alpha 1(I)CB7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192272 TI - Victimization of children. AB - Children suffer more victimizations than do adults, including more conventional crimes, more family violence, and some forms virtually unique to children, such as family abduction. On the basis of national statistics, these victimizations can be grouped into three broad categories: the pandemic, such as sibling assault, affecting most children; the acute, such as physical abuse, affecting a fractional but significant percentage; and the extraordinary, such as homicide, affecting a very small group. They can also be differentiated by the degree to which they result from the unique dependency status of children. A field called the victimology of childhood should be defined that adopts a developmental approach to understanding children's vulnerability to different types of victimizations and their different effects. PMID- 8192273 TI - Training professional psychologists for the twenty-first century. AB - The continued growth and development of professional psychology may ultimately stand or fall on the integrity of the educational system that prepares future generations of practitioners. Currently, the educational enterprise is unduly hampered by several significant impediments. These impediments are identified and resolutions are proposed that would, if implemented, greatly enhance psychology's ability to assume its rightful place as a major autonomous profession that is properly positioned to address some of the nation's pressing social needs. PMID- 8192274 TI - A PsyD degree for every practitioner. Truth in labeling. AB - At present, nearly 70% of APA members are identified as health care providers. The PhD degree, a generic scholarly degree, is most commonly used to certify completion of doctoral studies in professional psychology. As a result, the consumer has difficulty determining which psychologist is qualified to provide health care. The Doctor of Psychology (PsyD) should identify those psychologists who provide doctoral-level health services. Licensed, qualified PhD psychologists could be awarded the PsyD retroactively on the basis of a credential review, as the JD degree was awarded to lawyers previously holding the LLB. Applicants for the PsyD would not relinquish their PhD degrees. Upon review and approval, they would identify themselves with both degrees: PsyD, PhD. Mechanisms for accomplishing the change are suggested. PMID- 8192275 TI - Effect of vitamin C on lipoproteins in healthy adults. AB - BACKGROUND: It has been suggested that vitamin C can modify the composition of lipoproteins in healthy subjects. OBJECTIVE: To determine the possible modification of lipid levels in the presence of vitamin C, and the effect of various doses on lipid levels. DESIGN: This is a sequential open clinical trial, where the same individuals are used as their own controls, and where the same observer at random administers 1 or 2 g of oral vitamin C during a month, followed by a further month without treatment. PATIENTS: 124 healthy volunteers of both sexes, between 17 and 74 years of age, whose lifestyle was not modified during the study. MEASUREMENT: At the beginning of the study a determination was made of lipid levels, risk factors such as age, physical activity, tobacco and alcohol use, weight and arterial pressure; at the end of the first month during vitamin C therapy, and again at the end of the second month without therapy, lipid levels were determined, namely, TG, TC, HDL-C, HDL2-C, HDL3-C, LDL-C, ApoA1, ApoB and Lp(a). RESULTS: After one month of treatment with 2 grams of vitamin C, a significant decrease of ApoB was observed, namely, 5.5% in females and 8% in males (p = 0.019). Vitamin C treatment shows the following differential data: a negative correlation of Lp(a) with HDL3-C, in both sexes; in males, the positive correlation of age with LDL-C and the negative correlation of tobacco with HDL-C disappear, positive correlations appear between physical activity and HDL-C, between tobacco and LDL-C, between weight and ApoB, between SBP and TG, and between DBP and ApoB; in females, the positive correlation between weight and TG, and the negative correlation between weight and HDL-C both disappear, negative correlations appear between physical activity and both TC and ApoB, between weight and HDL3-C, a positive correlation appears between DBP and HDL2-C. Compared to non-drinkers, in males who consume less than 50 grams of alcohol daily, vitamin C produces a significant decrease in DHL3-C, while the significant increase in Lp(a) disappears. CONCLUSIONS: From the results in the follow-up of this group of healthy individuals, it can be deduced that vitamin C produces a decrease in ApoB in both sexes where 2 g are administered daily. When the risk factors are correlated, the results vary substantially, particularly with reference to the sex of the individuals. Women benefit much more than men from vitamin C therapy, especially when physical activity, weight and diastolic blood pressure are considered. Compared to non-drinkers, male drinkers demonstrate a decrease in HDL3-C, and the significant increase in Lp(a) disappears. PMID- 8192276 TI - [Anatomo-clinical conference. Pitie-Salpetriere Hospital. Case N.1-1994. Multiple hepatic tumors in a woman with idiopathic thrombopenic purpura]. PMID- 8192277 TI - [Gougerot-Sjogren syndrome: the viruses in the box of the accused]. PMID- 8192278 TI - [Interview with Pierre Godeau, President of the Societe Nationale Francaise de Medecine Interne. What is going to happen tomorrow in internal medicine?. Interview by Pierre Youinou]. PMID- 8192279 TI - Does a glycosylation defect of IgG reduce their binding to the corresponding receptors? PMID- 8192280 TI - [Electrophysiological study of diabetic neuropathies]. PMID- 8192281 TI - [Omega-3 unsaturated fatty acids: therapeutic applications]. PMID- 8192282 TI - [Systemic lupus erythematosus, antiphospholipid antibodies and severe arterial hypertension]. PMID- 8192283 TI - [Adrenomyeloneuropathy and adrenoleukodystrophy: genetic identity and detection. Apropos of a family]. PMID- 8192284 TI - [Cardiorespiratory arrest after injection of Spasfon (phloroglucinol trimethylphloroglucinol]. PMID- 8192285 TI - [Thrombosis of the inferior vena cava with pulmonary embolism in hepatic amebiasis]. PMID- 8192286 TI - [Incidence of serological markers of hepatitis B and C viruses and HIV in a population of drug abusers hospitalized from 1990 to 1992]. AB - Data on drug abusers collected at the Pharmacodependence centre of the Moselle (IPM) from 1990 to 1992 was used to establish the prevalences of hepatitic B and C viruses (HBV, HCV) and human immunodeficiency virus (HIV) and the clinicobiological type of the subjects infected with the HBV. Transaminase levels in HCV positive subjects was measured and a correlation was looked for between the serology status and age and duration of drug abuse. The prevalence for seropositivity for HBV and HCV was higher than for HIV, and the prevalence of HCV was higher than that of HBV (in 1992: HIV+ = 8.2%, HBV+ = 46.7%, HCV+ = 71.2%; n = 184). Less than one third of the study population was totally seronegative. It thus appeared that preventive measures against HIV have not been effective against HBV or HCV, especially that drug abusers know little about these viruses. HBV and HCV prevalences should be evaluated separately. The risk of chronic HBV infection was low (estimated at 10%) and contamination in drug abuses came later than for HCV. Seroprevalence of HBV was 46.7% in 1992 in the study population. The risk of chronic HCV infection was 50% and contamination came earlier than for HBV. Seroprevalence of HCV was 71.2% in 1992 in the study population. In the same population, the seroprevalence of HIV was 8.2%. For these drug abusers, the risk of HCV contamination was comparable with that of HIV infection. The main efforts for prevention and care in drug abusers should be concentrated on HIV then on HCV. PMID- 8192287 TI - All effective treatment could be free. PMID- 8192288 TI - Randomized trials in perinatology: major achievements and future potential. PMID- 8192289 TI - Some evaluation needs. PMID- 8192290 TI - The science of reviewing research. PMID- 8192291 TI - Publication bias: the problem that won't go away. AB - Conclusions about the efficacy and safety of medical interventions are based on data presented in the scientific literature. The validity of these conclusions is threatened if publication bias results from investigators or editors making decisions about publishing study results on the basis of the direction or strength of the study findings. This paper reports meta-analyses performed using data from four prospective investigations in which a total of 997 initiated studies were followed to learn of study results, publication status, and reasons for nonpublication. The analysis indicates that there is a positive association between "significant" study results and publication (OR = 2.88; 95% confidence interval [CI] 2.13 to 3.90). When the analysis was restricted to controlled trials (n = 280), an even stronger relationship between "significant" results and publication was observed (OR = 6.15; 95% CI 2.24 to 16.92), with randomized trials (n = 200) apparently no less susceptible to publication bias than controlled trials in general (OR = 8.72; 95% CI 1.91 to 39.81). In every case, failure to publish was investigator-based, and not due to editorial decisions. The results of clinical trials should not be suppressed in this way. Development of registration systems for randomized trials is essential if this problem is to be minimized in future. PMID- 8192292 TI - Collaborative worldwide overviews of randomized trials. AB - Formal overviews (or meta-analyses) are now widely accepted as the most reliable way to evaluate the evidence from several randomized controlled trials that have all assessed a particular form of therapy. If a limited amount of trial data has accumulated, overviews can be undertaken at a relatively simple level, assembling just summary data extracted from published reports. Such overviews are likely to be incomplete and biased and may (because of the restricted number of analyses that are possible) not answer all the clinically important questions that might be addressed. Where a particularly large body of data from randomized trials has accumulated, more thorough and detailed overview analyses are needed. Such detailed reviews are greatly facilitated if a collaborative group of all the trialists is formed. Such groups have sought to collate individual patient data (a very few key items for every patient randomized). A central statistical secretariat then coordinates the process of data collection, checking, and analysis. Analyses are presented to the whole group for discussion and final reports are published in the name of the whole group. Experience from two very large groups that have followed this model, the Antiplatelet Trialists' Collaboration and the Early Breast Cancer Trialists' Collaborative Group, has shown that detailed collaborative overviews have many benefits: the results are particularly clear and therefore have substantial public health impact; the areas of statistical and medical agreement on the evidence can be defined; the areas of uncertainty (and hence future research priorities) are clarified; and the group can disseminate the results particularly widely and rapidly. PMID- 8192293 TI - The Cochrane collaboration: preparing, maintaining, and disseminating systematic reviews of the effects of health care. AB - In an influential book published more than twenty years ago, Archie Cochrane drew attention to our great collective ignorance about the effects of health care, and explained how evidence from randomized controlled trials (RCTs) could help us to use resources more rationally. He recognized that people who want to take more informed decisions about health care do not have ready access to reliable reviews of the available evidence. In 1979, he wrote: "It is surely a great criticism of our profession that we have not organised a critical summary, by specialty or subspecialty, adapted periodically, of all relevant randomised controlled trials." The Cochrane Collaboration has evolved in response to this challenge and will eventually cover all areas of health care. Contributors in many countries and specialties are preparing and maintaining systematic reviews of RCTs, and reviews of other evidence when appropriate. These reviews will be disseminated using electronic media through the Cochrane Database of Systematic Reviews. PMID- 8192294 TI - Dissemination of medical information: a journal's role. PMID- 8192295 TI - Observational evidence. PMID- 8192296 TI - NIH consensus conferences: dissemination and impact. PMID- 8192297 TI - Bringing the news to the public: the role of the media. PMID- 8192298 TI - Some problems in applying evidence in clinical practice. AB - There is a considerable gap between sound evidence concerning health care interventions and the services that patients actually receive as health care. Practitioners and the health care system must overcome a number of barriers to narrow the gap. Viewed simplistically, there are three steps from evidence to practice: getting the evidence straight; developing clinical practice guidelines that are faithful to both the evidence and the clinical and personal situations of patients; and applying these guidelines to the right patient at the right time in the right way. Special problems in getting the evidence straight stem from difficulties in finding sound evidence. Lack of agreement on evidence standards undermine the effectiveness of authoritative practice guidelines. Applying evidence and practice guidelines effectively and efficiently is often thwarted by mismatches between evidence and usual practice circumstances. Time pressures undermine interpretation and application of evidence at every step. Understanding these problems may permit development of more effective strategies to bridge the gap between evidence and practice. PMID- 8192299 TI - Diffusion, dissemination, and implementation: who should do what? AB - The concepts of diffusion, dissemination, and implementation are distinguished as progressively more active steps in the process of flowing valid and reliable research information into clinical practice. Using a staged model of behavior change, diffusion is seen as a precursor for dissemination activities, which in turn "predispose" physicians to consider change in their practices. Local implementation activities capitalize on this by "enabling" and subsequently "reinforcing" the desired behavior change. Different skills are needed for each activity. Biomedical journals, with some improvements, are identified as diffusion agents. Collaboration between academics and medical organizations is best suited to the dissemination stage. Local agents, empowered by resources, are best equipped for implementation activities. PMID- 8192300 TI - Using evidence to teach effective use of health interventions. PMID- 8192301 TI - Can we learn anything from small trials? AB - In summary, then, we can learn three useful things from small clinical trials. First, we can learn when to challenge conventional but untested therapeutic wisdom. Second, because the patient number in any trial is the number of events, rather than the number of study patients, some small trials are so definitively positive that they are sufficient to identify the best therapy. And third, small trials, even when individually inconclusive, can serve as the basis for convincingly conclusive overviews and meta-analyses that carry, and deserve, greater credibility than a single large trial of similar size to their sum. PMID- 8192302 TI - Public health education. PMID- 8192303 TI - Using evidence to teach clinical epidemiology. PMID- 8192304 TI - Continuing education for medical practice. PMID- 8192305 TI - The clinical efficacy assessment program of the American College of Physicians. AB - The experience of the American College of Physicians (ACP) in evaluating the clinical literature and publishing clinical guidelines spans more than a decade. The ACP uses an evidence-based method for the development of clinical practice guidelines for diagnostic technologies and treatments. The approach of the Clinical Efficacy Assessment Program (CEAP) involves collation, methodologic review, and analysis of the clinical literature. The process focuses on the safety, contraindications, efficacy, limitations, and cost of diagnostic technologies or treatments. To ensure a balanced perspective of the evidence, methodologic and content experts cooperate to prepare a summary paper. Strengths of this evidence-based approach include: (1) focus on the needs of practicing internists; (2) identification of all pertinent clinical literature; (3) integration of expert opinion when literature is inadequate; (4) recommendations based on high-quality scientific evidence; (5) preparation of conservative guidelines when evidence is lacking; and (6) reevaluation of past guidelines as new evidence becomes available. Limitations of the process include: (1) access only to published research; (2) use of criteria for scientific quality that are not standardized across projects; (3) published recommendations based on small numbers of high-quality research products; (4) compromise with expert opinion when evidence is limited; and (5) ad hoc management of conflict between experts when scientific evidence is sparse. The process produces credible recommendations that may improve physician knowledge and acceptance of practice guidelines. PMID- 8192306 TI - Using evidence for utilization management: an HMO manager's perspective. PMID- 8192307 TI - The role of evidence in the approval of pharmaceuticals. PMID- 8192308 TI - Health care reform in the United States. The contribution of health services research to the debate. PMID- 8192309 TI - Using evidence: the role of foundations. PMID- 8192310 TI - Financing medical effectiveness research: role of the Agency for Health Care Policy and Research. PMID- 8192311 TI - Alternative medicine. PMID- 8192312 TI - Summation of the conference. PMID- 8192313 TI - Large-scale randomized evidence: large, simple trials and overviews of trials. PMID- 8192314 TI - Doing good before there's harm. PMID- 8192315 TI - On the proper use of clinical trials. PMID- 8192316 TI - Regional organization for outcomes research. AB - Methods for achieving improvement in medical and surgical outcomes are often discussed, but rarely achieved. We report on a regional voluntary consortium founded in 1987 to provide information about the management of cardiovascular disease in northern New England. Members include all cardiothoracic surgeons and interventional cardiologists in the region, as well as administrators and scientists associated with the five institutions that provide advanced cardiac services in this region. The group maintains registries for coronary artery bypass grafting, coronary angioplasty, and heart valve surgery and has investigated institutional differences in mortality rates; the development and use of clinical prediction rules; the reasons for excess mortality among women undergoing bypass graft surgery; and time trends in the use of myocardial revascularization. This consortium is an inter-institutional model for the continuous improvement of medical and surgical care. PMID- 8192317 TI - Doing more good than harm. PMID- 8192318 TI - Outcomes research, PORTs, and health care reform. PMID- 8192319 TI - Use of claims data to monitor patients over time: acute myocardial infarction as a case study. PMID- 8192320 TI - Using scientific information to improve quality of health care. PMID- 8192321 TI - Patient outcomes research teams: examples from a study on knee replacement. PMID- 8192322 TI - Randomized control trials and meta-analyses in gastroenterology: major achievements and future potential. PMID- 8192323 TI - Primordial immunity: foundations for the vertebrate immune system. Introduction. PMID- 8192324 TI - Development of an immune system. AB - Minimally, an immune response is an induced cellular and/or humoral defense mechanism specific for the challenging agent. The system is a cognitive one inasmuch as a second stimulus with the same antigen can specifically induce either an enhanced response (memory) or diminished response (tolerance). The cells responsible for the initial antigen-specific recognition in higher vertebrates are clonally restricted T and B lymphocytes. Accessory cells are necessary for the processing and presentation of antigen, and physiologic mediators (cytokines) are essential for proliferation, interaction, and regulation of the system. Although it now appears that the recombination mechanisms essential for the anticipatory immune response occurred late in the deuterostome stream leading to vertebrates, molecules required for cell adhesion and regulation are widely spread in phylogeny. Their emergence must have preceded the divergence between ancestral protostomes and deuterostomes. Genetic mechanisms underlying the generation of diversity in the light and heavy chains of antibodies of mammals may be quite distinct in primitive vertebrates, particularly elasmobranchs, the ancestors of which diverged from those of mammals more than 400 million years ago. Despite this, clonal selection of antigen receptors of lymphocytes is most probably universal within the vertebrates. There is no need to force induced recognition in protostomes (e.g. insects) or lower deuterostomes (e.g. echinoderms) into mammalian models of immunity. PMID- 8192325 TI - Role of hemocyte-derived granular components in invertebrate defense. AB - Figure 2 illustrates an outline of the cellular and humoral defense systems in limulus. On the basis of the knowledge described above, it is suggested that granular components present in L and S granules in the hemocytes play a decisive role in the biological defense for this animal. The isolated L granules contain at least three clotting factors plus coagulogen as the major component. The known anti-LPS factor and a number of additional unknown protein components are also present in the L granules. On the other hand, the isolated S granules contain antimicrobial tachyplesins as the major component, in addition to six unidentified proteins. We speculate that the L-granule-derived protein components, which probably contain all the factors essential for the Limulus clotting system participate, in immobilizing invading microbes, and that the S granule-derived tachyplesins contribute to a self-defense system against invaders. Although we have not mentioned hemolymph plasma components, there are many humoral factors, such as proteinase inhibitors, alpha 2-macroglobulin, various lectins, C-reactive protein, and polyphemin, all of which are important for antimicrobial defense. Furthermore, Liu and colleagues have reported several endotoxin-binding proteins and a cell-adhesion protein found in the Limulus hemocytes. Although the exact functions of these substances are unknown, they may act in concert with other components to provide biological defense for the animal. Nevertheless, compared to our knowledge of mammalian blood cells, much less remains to be learned of biological/physiological events in horseshoe crab hemocytes. PMID- 8192326 TI - Regulation of antibacterial protein synthesis following infection and during metamorphosis of Manduca sexta. AB - Larvae of the tobacco hornworm, Manduca sexta, respond to intrahemocoelic injection of bacteria or bacterial cell wall peptidoglycan with induced synthesis of a suite of antibacterial proteins. Previous studies have demonstrated peptidoglycan regulation of the synthesis of these antibacterial proteins. In addition to eliciting enhanced synthesis of antibacterial proteins, peptidoglycan fragments also elicit a "malaise syndrome" characterized by decreased feeding and growth, delayed metamorphosis, and altered excretion. We speculate that these symptoms may be components of a mechanism to flush out and sterilize the midgut lumen, one of the primary sources of bacterial infection in insects. Studies of naive larvae have demonstrated the accumulation of lysozyme in the differentiating pupal midgut epithelium and release of lysozyme into the pupal midgut lumen after the larval midgut epithelium has been sloughed off. These observations have been extended by the identification of potent bactericidal activity against E. coli and immunoreactive hemolin, together with lysozyme, in the lumen of the newly differentiated pupal midgut. PMID- 8192327 TI - MHC evolution and development of a recognition system. AB - The unrestricted viability of allophenic mice shows that MHC-different cell lines have no problem engaging in organogenesis together. Thus, outside of the immune system, mammals appear to have no self-non-self discrimination mechanism based on polymorphic and ubiquitously expressed class I MHC antigens. Here, it should be pointed out that even within the immune system, certain responses require no self non-self discrimination, for example, antiphosphocholine response and certain antipolysaccharide responses that exploit differences between bacterial and host sugar transferases. Thus, the self-non-self discrimination via peptide fragments presented by ubiquitously expressed class I MHC antigens can be viewed as the late addition that enabled the adaptive immune system to cope with intracellular parasites that are primarily viruses. The preference for different types of peptide fragments suffices to explain extensive polymorphism as well as multiple gene loci for class I and possibly also class II MHC antigens. Yet, a too specialized class I MHC allele that presents a very unusual peptide fragment is of no use, for such a peptide fragment is not likely to be found among viral proteins. Effective MHC antigens are those that prefer common enough peptide fragments, so that at least one T epitope can be found in one out of every three viral proteins. Yet, such common peptide fragments are also likely to be present among multitudes of intracellular proteins that are the self. The immune system appears to have solved the above dilemma by mounting a vigorous cytotoxic T-cell response only when viruses are actively propagating by synthesizing a few of their own proteins in large amounts, thereby suppressing the host protein synthesis. To attack infected cells in which viruses are in the quiescent state of symbiosis with the host is the ultimate folly. PMID- 8192328 TI - C-reactive proteins, limunectin, lipopolysaccharide-binding protein, and coagulin. Molecules with lectin and agglutinin activities from Limulus polyphemus. AB - In 1964, Levin and Bang discovered that gram-negative bacterial endotoxin could rapidly induce gelation of Limulus amebocyte lysate. This observation has led to the development of the most sensitive and specific method for the detection of bacterial endotoxin in pharmaceuticals and drugs intended for human use. Over 10 years ago, Bang injected endotoxin into young horseshoe crabs and observed a time and dose-dependent coagulation of the whole hemolymph. Limunectin, LEBP-PI, and Limulus CRP are found together with coagulin as part of the hemolymph clot at the time of endotoxin-induced exocytosis of amebocytes. In this manner, these molecules with agglutinin/lectin activities could work in concert to assist in the recognition and eventual removal of invading microorganisms from the circulating system. Although the mechanism of endotoxin-induced clot formation is to a large extent understood, the mechanism of clot dissolution and removal in the Limulus hemolymph remains to be clarified. PMID- 8192329 TI - The prophenoloxidase activating system and its role in invertebrate defence. PMID- 8192330 TI - Phagocytosis and invertebrate opsonins in relation to parasitism. PMID- 8192331 TI - Ciliate pheromones as early growth factors and cytokines. PMID- 8192332 TI - Cell surface recognition and the immunoglobulin superfamily. AB - Immunoglobulins serve as humoral recognition and effector molecules and as antigen-specific cell surface receptors on B and T cells. These molecules are constructed according to a characteristic domain pattern. Variable and constant domains diverged from one another early in vertebrate evolution, and they are joined by a "switch peptide" specified by the joining gene segments. Peptides specified by J-gene segments are strongly conserved in evolution in comparison among Ig light chains and T-cell receptors. Molecules less strongly related to Ig domains have been assembled into an Ig "superfamily" where the identities to classical IgC or V domains are < or = 20%. Among these are cell surface adhesion molecules, receptors for cytokines, and Fc receptors. Moreover, MHC antigens have an Ig-like membrane-proximal domain significantly related to IgC regions. We will analyze putative evolutionary relationships among canonical Igs and members of the Ig superfamily using highly conserved sequences from light and heavy chains of primitive vertebrates (e.g., the sandbar shark) as prototypes to ascertain similarities between Ig-related molecules of vertebrates and invertebrates. PMID- 8192333 TI - The echinoderm immune system. Characters shared with vertebrate immune systems and characters arising later in deuterostome phylogeny. AB - In summary, the characters of the echinoderm immune system that we review here can be considered to illuminate the baseline nonadaptive immune systems that were our original deuterostome heritage. We still retain--and greatly rely upon- similarly functioning, nonadaptive cellular defense systems. It is worth stressing that sea urchins are long lived, normally healthy animals that display remarkable abilities to heal wounds and combat major infections. From an external point of view, their immune systems obviously work very well. Thus, their cellular defense systems are extremely sensitive, and they respond rapidly to minor perturbations, all without any specific adaptive capabilities. These systems probably function through the transduction of signals conveying information on injury and infection, just as do the equivalent systems that underlie and back up our own adaptive immune systems, and that provide the initial series of defenses against pathogenic invasions. Many extremely interesting questions remain regarding the evolution of the deuterostome immune response. Are the echinoderm and tunicate systems the same, or have the protochordates augmented the basic phagocyte system with an as yet unidentified chordate-like character? Do the jawless fishes produce Igs that would make them similar to the sharks, or are they vertebrates without an Ig system that essentially rely on an invertebrate-like, nonspecific, activated phagocyte type of immune system? How do sharks regulate their immune system without T cells and MHC class I? How do they avoid producing autoantibodies? Future research will not only answer these questions, but those answers will also be enlightening with regard to the origins of the mammalian immune system in which ancient functions and subsystems remain. PMID- 8192334 TI - Tumor-suppressor genes, hematopoietic malignancies and other hematopoietic disorders of Drosophila melanogaster. PMID- 8192335 TI - Chemical toxicity and host defense in earthworms. An invertebrate model. PMID- 8192336 TI - Immunomodulation by didemnins. Invertebrate marine natural products. PMID- 8192337 TI - A novel solid-phase assay for lectin binding. Comparative studies on beta galactoside-binding S-type lectins from fish, amphibian, and mammalian tissues. PMID- 8192338 TI - Elasmobranch and teleost fish contain thiol-dependent beta-galactoside-binding lectins that are cross-reactive with those identified and characterized in bovine spleen. PMID- 8192339 TI - Hemolymph lectins of the blue crab, Callinectes sapidus, recognize selected serotypes of its pathogen Vibrio parahaemolyticus. PMID- 8192340 TI - A dimeric lectin from coelomic fluid of the starfish Oreaster reticulatus cross reacts with the sea urchin embryonic substrate adhesion protein, echinonectin. PMID- 8192341 TI - Blood cell-mediated cytotoxic activity in the solitary ascidian Ciona intestinalis. PMID- 8192342 TI - Induction of a cellular defense reaction is accompanied by an increase in sensory neuron excitability in Aplysia. PMID- 8192343 TI - Quantitation of lectin binding by cells harvested from the spleen and anterior kidney of the Japanese medaka (Oryzias latipes). PMID- 8192344 TI - Identification of AU-rich 3' untranslated regions in mRNA from sea urchin coelomocytes. PMID- 8192345 TI - Rapid allogeneic recognition in the marine sponge Microciona prolifera. Implications for evolution of immune recognition. PMID- 8192346 TI - The isolation of putative major histocompatibility complex gene fragments from dogfish and nurse shark. PMID- 8192347 TI - Neuroendocrine markers expressed on sea urchin coelomocytes and other immunoregulatory parameters may be used to monitor environmental changes. PMID- 8192348 TI - Phylogeny of the third complement component, C3, and conservation of C3-ligand interactions. PMID- 8192349 TI - Hemocyte involvement in muscle cell death in flies. PMID- 8192351 TI - Transplantation immunity in the sea anemone Condylactis gigantea. PMID- 8192350 TI - A possible immunomodulatory role of endozepine-like peptides in a tunicate. PMID- 8192352 TI - Evolution of teleost antibody genes. PMID- 8192353 TI - Animal lectins as self/non-self recognition molecules. Biochemical and genetic approaches to understanding their biological roles and evolution. AB - In recent years, the significant contributions from molecular research studies on animal lectins have elucidated structural aspects and provided clues not only to their evolution but also to their multiple biological functions. The experimental evidence has suggested that distinct, and probably unrelated, groups of molecules are included under the term "lectin." Within the invertebrate taxa, major groups of lectins can be identified: One group would include lectins that show significant homology to membrane-integrated or soluble vertebrate C-type lectins. The second would include those beta-galactosyl-specific lectins homologous to the S-type vertebrate lectins. The third group would be constituted by lectins that show homology to vertebrate pentraxins that exhibit lectin-like properties, such as C-reactive protein and serum amyloid P. Finally, there are examples that do not exhibit similarities to any of the aforementioned categories. Moreover, the vast majority of invertebrate lectins described so far cannot yet be placed in one or another group because of the lack of information regarding their primary structure. (See Table 1.) Animal lectins do not express a recombinatorial diversity like that of antibodies, but a limited diversity in recognition capabilities would be accomplished by the occurrence of multiple lectins with distinct specificities, the presence of more than one binding site, specific for different carbohydrates in a single molecule, and by certain "flexibility" of the binding sites that would allow the recognition of a range of structurally related carbohydrates. In order to identify the lectins' "natural" ligands, we have investigated the interactions between those proteins and the putative endogenous or exogenous glycosylated substances or cells that may be relevant to their biological function. Results from these studies, together with information on the biochemical properties of invertebrate and vertebrate lectins, including their structural relationships with other vertebrate recognition molecules, are discussed. PMID- 8192354 TI - Recognition molecules and immunoglobulin domains in invertebrates. AB - We have used specific antibody probes to conserved antigenic motifs to identify and characterize immunoglobulin-related molecules in tunicates and a C-type lectin found in lamprey that is related to molecules found in tunicates and mammals. The tunicate immunoglobulin cross-reactive molecule (mu CRM) reacts with antibodies raised to shark IgM heavy chains. Intact tunicate mu CRM is a monomer of Ig light-chain-sized subunits and is oligoclonal by IEF. That this molecule is related to Ig is indicated both by immunochemical data and by peptide sequence homologies. The lamprey lectin is a large polymer (> 500,000 kDa) of 35-kDa and 60-kDa subunits. It appears to be related to C-type lectins as shown by peptide sequence homology and the requirement of Ca2+ for activity. Related molecules appear to be present in tunicates and mammals as shown by cross-reactivity of antibodies in Western blots with single bands from hemolymph and T-cell extracts. PMID- 8192355 TI - Evolution of adaptive immunity: inducible responses in the American cockroach. PMID- 8192356 TI - Autoimmunoregulation and the importance of opioid peptides. PMID- 8192357 TI - The versatile superficial inferior epigastric flap for breast reconstruction. AB - The superficial inferior epigastric flap is a versatile free flap that has added to the techniques available for autogenous breast reconstruction. It is especially advantageous when previous thoracic radiation and/or abdominal surgery preclude the use of conventional transverse rectus abdominis musculocutaneous flaps. Eight superficial inferior epigastric flaps were used to reconstruct 7 breasts in 6 patients. In 4 patients the superficial inferior epigastric flap was used as part of a composite free flap. In 1 patient, a lower abdominal wall flap was transferred on bilateral pedicles. In another, bilateral flaps were raised to reconstruct both breasts. The superficial inferior epigastric flap offers several advantages. It uses relatively abundant lower abdominal wall skin and subcutaneous tissue while preserving the underlying fascia and rectus muscles. A cadaver study illustrates the clinical territory of this flap. The superficial inferior epigastric flap provides an excellent option for autogenous free flap reconstruction of the breast, alone or in combination with other flaps. PMID- 8192358 TI - Fibroblast behavior in vitro is unaltered by products of staphylococci cultured from silicone implants. AB - Our previous clinical study supported the concept that capsular contracture is associated with subclinical infection of silicone implants. If bacterial presence, indeed, contributes to capsular contracture, then fibroblast behavior might be expected to change in the presence of bacteria by-products. Therefore, study of possible alteration of fibroblast behavior by bacteria products was undertaken using an in vitro model with cultured dermal fibroblasts. Coagulase negative staphylococci from silicone mammary and penile implants were isolated and their phenotypic features were characterized. All represented nonbiofilm producing strains. Products of isolate cultures were noncytotoxic and did not alter matrix reorganization (collagen gel contraction model) or collagen production by fibroblasts. Isolates from either mammary or penile implants exerted similar effects. PMID- 8192359 TI - Growth potential of autogenous cartilage grafts in expanded skin: an experimental study in rabbits. AB - The effect of tissue expansion on the growth potential of autogenous cartilage grafts was studied in 10-day-old New Zealand white rabbits. The rabbits were divided into two groups: In Group 1 (n = 12) after 2 weeks of tissue expansion by using a 10-ml tissue expander, a cranially based 4 x 4-cm dorsal skin flap was raised and a 1 x 1-cm autogenous cartilage graft from the midportion of the left ear was transplanted beneath the flap in each rabbit. In Group 2 (n = 12) elevation of dorsal skin flaps and transplantation of the grafts were performed in the same way but without a previous tissue expansion. The grafts were removed at 30 and 60 days after transplantation in both groups, for histological examination and measurement of the dimensional changes to determine the growth rate. In both groups, histological examination revealed characteristic findings for cartilage growth, however, Group 1 (expansion) demonstrated a statistically significant increase in the growth of cartilage grafts when compared with Group 2 (control) (p = 0.0001). The results of this study indicate, from the standpoint of acceptance and growth potential of autogenous cartilage framework, that there is no drawback to using this tissue expansion technique for reconstruction of the ear in childhood. PMID- 8192360 TI - The effect of frostbite on the reconstructed ear. AB - A 17-year-old patient whose left ear was reconstructed using a lateral arm fascia and skin graft had done well until one episode of cold exposure approximately two years after the reconstruction. This thermal injury resulted in a localized area of composite tissue loss demonstrating that the reconstructed ear had a higher susceptibility to cold temperatures. The transferred fascia did, however, allow a stable base for granulation and reepithelialization, showing the continued vascularity and regenerative capacity of the transferred tissue. A discussion is provided regarding the susceptibility of free transferred fascia and its regenerative capacity. PMID- 8192361 TI - Comparative study of auricular dimensions for the normal auricles of microtia patients, their parents, and normal individuals. AB - We measured the dimensions of the normal auricle in microtia patients and those of both auricles in their parents, and compared the findings with data obtained in normal individuals. The physiognomical auricular length and width dimensions of the normal auricles in microtia patients were significantly smaller than those in normal individuals. The auricular length of the parents of microtia patients was also significantly smaller than in normal individuals. The auricles of the parents on the same side as those affected by microtia in the patients tended to be smaller than those on the contralateral side. PMID- 8192362 TI - Compartment syndrome in children. AB - The development of compartment syndrome is a well-recognized clinical entity. The diagnosis and management of compartment syndrome in the adult population is well established. Because of the difficulty with cooperation in physical examination of children with pain, the early recognition of compartment syndrome in this group of patients can be more challenging. Furthermore, the potential inability to make a prompt and accurate diagnosis can lead to significant extremity morbidity and possibly mortality. PMID- 8192363 TI - Reconstruction of very short humeral stumps. AB - Satisfactory functional prosthetic management of the very short humeral stump is difficult, and reliable methods for humeral lengthening in this circumstance are lacking. For this reason, we have developed a lengthening procedure that uses a latissimus dorsi musculocutaneous flap with incorporated eighth, ninth, or tenth rib. The flap may be elevated without detaching its vascular pedicle. Two patients have been successfully rehabilitated with prosthetics following this procedure. PMID- 8192364 TI - Extradural dead space following cranial bone advancement. AB - The extradural dead space produced after enlargement of the intracranial space or after reduction of the volume of the intracranial contents persists for an unknown period of time. To investigate this further, an extradural dead space was surgically created by advancement of parietal bones in 9 adult rabbits. By design, there was no connection with the paranasal sinuses. To determine outcome of the dead space, three-dimensional computed tomographic and histological studies were performed. The brain volume decreased in the first 3 months after surgery and remained constant for up to 9 months. The extradural volume increased in the first 4 weeks postoperatively, gradually decreasing in size with time. The brain failed to eliminate the extradural dead space by rearrangement or expansion. An osseous cavity filled with fluid and connective tissue was formed within the dead space. The fluid within it remained, even 9 months after surgery. This could be a potential environment for bacterial invasion if there was a connection with the nasopharynx. PMID- 8192365 TI - Reconstruction of defects of the anterior cranial fossa during craniofacial tumor resection. AB - Following removal of sizable craniofacial tumors, large defects in the dura of the anterior cranial fossa usually result. Neither the temporal fascia nor the temporal muscle will customarily reach far enough to close these anterior defects. A de-epithelialized forehead flap with an inferior base may be transposed into the defect to achieve watertight closure, even with a large defect. Eight cases are presented in which this method was successfully used. PMID- 8192366 TI - Plagiocephaly: premature unilateral closure of the coronal suture: a potentially localized disorder of cellular metabolism. AB - Osteoblasts from involved and noninvolved sutures and normal membranous bone in patients with premature unilateral coronal synostosis were harvested and grown in tissue culture. The cultures were characterized to establish specific basal metabolic parameters of cellular growth and the production of metabolites, including osteocalcin, alkaline phosphatase, platelet-derived growth factor, epidermal growth factor, tumor necrosis factor-alpha, and DNA. In addition, metabolic responses to two provocative bone trophic agents, parathyroid hormone and 1,25dihydroxyvitamin-D3 were ascertained. Osteoblasts from involved sutures (involved bone) exhibited altered indices of cellular metabolism when compared with osteoblasts derived from noninvolved sutures (noninvolved bone) in a basal state and when exposed to parathyroid hormone and vitamin D3 (p < or = 0.05). Involved osteoblasts produced significantly more osteocalcin and significantly less alkaline phosphatase than noninvolved osteoblast-derived cultures (p < or = 0.05). Secretion of platelet-derived growth factor and epidermal growth factor was also altered in the involved osteoblasts compared with the noninvolved osteoblasts (p < or = 0.05). Secretion of tumor necrosis factor-alpha was not significantly different between involved and noninvolved osteoblast-derived cultures. PMID- 8192367 TI - Long-term follow-up study of browlift for treatment of facial paralysis. AB - Browlift for patients with irreversible paralysis of the frontalis muscle was evaluated in a review of 40 patients who had undergone follow-up studies for durations of more than 3 years. The procedure consists of a lazy S-shaped excision above the upper border of the eyebrow and upward fixation of the lower skin margin. The results were as follows: (1) The percentage of patients for whom symmetrical positioning of the eyebrow was achieved was 65%. (2) The greater the preoperative severity of ptosis, the more often did recurrence occur. (3) Recurrence progressed rapidly during the first postoperative year, but thereafter recurrence was seen only in those patients in whom the affected eyebrow was still in a position higher than its counterpart. (4) No relationship could be seen between age at the time of surgery and postoperative position of eyebrow. (5) Improvement in contraction of the visual field was seen in 85% of patients postoperatively, and complaints were eliminated in 50%. (6) Careful preservation of the sensory nerve is required. (7) The postoperative scar was acceptable. This procedure is a simple and effective method of correction of paralytic ptosis. Although a degree of skill is required to obtain satisfactory results and a surgical scar remains at the upper border of the eyebrow, the advantages of the procedure surpass its disadvantages. It is believed that this method should be used more often in the treatment of facial paralysis. PMID- 8192368 TI - Simultaneous quantitation of facial movements: the maximal static response assay of facial nerve function. AB - An assay is described that enables the simultaneous measurement of bilateral facial movements within zones relevant to facial nerve function. The assay allows the accurate quantitation of movement of the eyebrows, radix, lower eyelids, philtrum, mentum, and oral commissures relative to these points on the resting face. Global or region-specific facial nerve dysfunction is detectable using this assay, as shown in examples of patients having single branch facial nerve palsy and bilateral facial palsy (Mobius syndrome variant). Because facial movement is tested by region, with the remainder of the face relaxed, synkinesis can be detected when present. The assay has potential to be used as an adjunct to the presently used ordinal scales of facial nerve function, by allowing actual quantitation of region-specific facial movement. This feature may prove helpful in vector planning for reanimation procedures and may allow the tracking of functional responses after such procedures, thereby providing a measurement of their efficacy. PMID- 8192369 TI - The effects of tretinoin on random skin flap survival in the swine model. AB - Tretinoin is currently marketed for topical treatment of acne vulgaris and has also been used in the rejuvenation of aging skin. After topical application, it has been shown to stimulate mitotic activity and increase vascularity in skin. In this study a porcine model was used to test the hypothesis that presurgical treatment with topical tretinoin would increase the surviving area of random full thickness skin flaps. Four hybrid barrows, 40 to 60 lb, were treated with tretinoin and 4 similar animals were treated with placebo (carrier vehicle) for 2 weeks before raising four dorsally based full-thickness skin flaps (4 x 12 cm) on each animal. Biopsies were taken from tretinoin-treated, placebo-treated, and untreated skin at the time the flaps were initially raised and 1 week later before killing the animals. All tissue was processed for light and electron microscopy. One week after surgery, the pigs were killed. Photographs were taken at the termination of the experiment and the negatives were digitized and analyzed using a high-speed graphics workstation supported by SGITrace software. The percentage of skin flap survival was determined using this method of image analysis. Using repeated-measures analysis of variance, there was no significant difference in the mean flap survival between the tretinoin (mean = 46.75; SEM = 7.05) and placebo (mean = 65.80; SEM = 7.05) treated groups at the 0.05 significance level. Pretreatment with tretinoin did not enhance skin flap survival under the conditions of this study. Rationale for this finding and possible modifications of future studies are discussed. PMID- 8192370 TI - Improvement of erythematous and hypertrophic scars by the 585-nm flashlamp-pumped pulsed dye laser. AB - Fourteen patients with erythematous and/or hypertrophic scars resulting from remote surgical excision or trauma were evaluated and subsequently treated with one to two flashlamp-pumped pulsed dye (585 nm) laser treatments over a 2-month period. Clinical assessments were performed before commencement and at the end of the study in all 14 patients. Skin surface texture analyses using optical profilometry were obtained from 5 of the patients before and after laser irradiation. A 57% to 83% clinical improvement was seen in the scars after one to two dye laser treatments, respectively. In addition, a change in the skin texture with return of skin markings approximating those of normal skin measured by optical profilometry was observed in the scars after the pulsed dye laser treatments. The degree of clinical improvement seen at the end of the study continued to be evident in each patient at the 6-month follow-up examination. PMID- 8192371 TI - Treatment of brachymetatarsia by callus distraction (callotasis). AB - Callus distraction (callotasis) has already become a popular procedure in the lengthening of limbs. With the development of a small device, it can also be applied to the hand or foot, thus providing benefits in the treatment of brachymetatarsia. Four toes of 3 patients with brachymetatarsia of the fourth toe were treated by this method, and excellent elongation of from 17.50 to 32.55 mm (average, 23.71 mm) was acquired. The treatment period ranged from 78 to 141 days (average, 112.5 days). More time was required in the earlier cases, but the most recent took only 11 weeks. The optimal distraction rate is considered to be 0.35 mm per half-day. Reshortening after treatment ranged from 3.6 to 5.5 mm (average, 4.7 mm), or from 15% to 26% (average, 20.5%) of the distracted length. About 90% of the resorption was observed within 1 month, except in a case that involved a postoperative fracture, and no resorption was seen after 2 surgical months. Regarding complications, subluxation of joints was seen in 2 patients and a postoperative fracture in 1 patient. Subluxation was caused by tendons resisting elongation. The procedure is described, representative cases are illustrated, and problems encountered are discussed. PMID- 8192372 TI - The radial forearm flap as a pedicled flap for resurfacing a scarred nose. AB - The radial forearm flap, applied as a free flap, has been shown to be very versatile, if covering a defect with a thin, flexible flap is of predominant importance. The advantage of this technique compensates for any disadvantages in the donor area. Under certain circumstances it is a better solution to design the radial forearm flap as a distant, vascular pedicled flap than to perform it as a free flap with microvascular anastomoses. In treatment of this patient we used a distally pedicled radial forearm flap to resurface a burned nose and to reconstruct the tip of the nose. In this case a scarred forehead prevented us from using an expanded forehead flap. The increased morbidity of a distant, pedicled flap was well accepted as the price for preventing additional scarring in the face, as would have occurred in the case of a free flap, through the exposure of vessels for the vascular anastomoses. PMID- 8192373 TI - Tissue-expanded visor flap in burn surgery. AB - Severe postburn scarring of the lower face in the adult male may cause loss of mustache and beard in addition to other complications. The resulting unacceptable boyish appearance in 3 such patients was treated with tissue-expanded visor flap reconstruction. Complications, which were few, minor, and temporary, included moderate postoperative hematoma, hair-bearing skin loss in the region of the sideburns, and hair growth in an unwanted direction. The flap is safe to perform, with adequate blood supply, and achieved the goal of the operation, which is the restoration of a masculine appearance. The major advantage of this procedure is that the donor site morbidity and alopecia associated with the classic visor flap is virtually eliminated. PMID- 8192374 TI - Combined paraumbilical perforator skin flap and vascularized pubic bone graft. AB - A severely depressed deformity of the buccal region was repaired with an osteocutaneous flap based on the deep inferior epigastric vessels. This osteocutaneous flap has not been previously described in the literature. The superior pubic ramus, supplied by pubic branches from the deep inferior epigastric vessels, forms the bony portion of the combined flap. The cutaneous portion is also supplied by the deep inferior epigastric vessels and its thickness can be adjusted. This combination is useful when requiring both a thin flap and a flat bone. PMID- 8192375 TI - Cross lip flap in vermilion reconstruction. AB - Lips may need to be repaired because of congenital malformations, benign or malignant tumors, or trauma. When a large portion of the lip is involved in the defect, or when this portion is cosmetically relevant, the repair may be particularly challenging and requires a perfect technique. We devised a surgical technique for the reconstruction of the vermilion that involves the use of a large portion of the mucosa vestibularis and of the underlying musculus orbicularis. The mucosa and muscle are taken from one lip and are rotated to cover the quantitative and qualitative defect of the opposite prolabium. Two stages are required in this procedure. PMID- 8192376 TI - Manpower in plastic surgery. PMID- 8192377 TI - The future of surgical specialty education. PMID- 8192378 TI - Are there too many of us? PMID- 8192379 TI - Re: The racket over numbers. PMID- 8192380 TI - Smooth versus textured expander implants: a double-blind study of capsule quality and discomfort in simultaneous bilateral breast reconstruction patients. AB - Textured silicone expanders are alleged to be less painful in the filling process, to have less capsular contracture, and to stay in position better than smooth silicone expanders. To test these three hypotheses, 6 patients undergoing bilateral simultaneous expander implant placement for breast reconstruction after mastectomy were studied. In a double-blind fashion, after smooth and textured implant placement (one in each side) and initial wound healing, each patient was sequentially expanded with equal volumes of saline. In each patient, at each expansion, pressure data, discomfort scores, and implant placement measurements were made. At implant removal, smooth and textured capsule tissues were studied for collagen type content and ability to contract the patient's own fibroblast populated collagen lattice. In 4 of 6 patients the smooth expander was associated with lower injection pressures and less discomfort. In all patients the expanders maintained their position, except in 1 patient whose smooth implant shifted laterally. The capsular collagen typing and fibroblast-populated collagen lattice studies demonstrated no difference between smooth and textured capsules. In this double-blind clinical study in simultaneous bilateral breast reconstruction patients we could not confirm the suggestion that textured silicone expanders produce less capsular contracture and cause less pain with injection. PMID- 8192381 TI - The free transverse rectus abdominis musculocutaneous flap for breast reconstruction: one center's experience with 211 consecutive cases. AB - All patients undergoing breast reconstruction with free transverse rectus abdominis musculocutaneous (TRAM) flaps from February 1989 to November 1992 were registered into a computerized database and followed prospectively. There were 211 free TRAM flap breast reconstructions in 163 patients; 48 reconstructions were bilateral. A muscle split technique was used in 108 of 211 reconstructions (51%). Total flap loss occurred in 3 of 211 reconstructions for a success rate of 99%. Complications occurred in 81 of 211 reconstructions (38%). Fat necrosis or partial flap loss occurred in 15 of 211 (7%). Hernia or bulge occurred in 11 patients (5%). The bulge/hernia rate tended to be lower in the muscle split group (4 of 108 [4%]) than in those who did not have muscle split procedures (7 of 103 [7%]), whereas the fat necrosis rate was slightly higher in the former group (9 of 108 [8%]) than in the latter (6 of 103 [6%]). Neither difference was statistically significant. However, patients who currently or previously smoked cigarettes did have a significantly higher incidence of fat necrosis: 12 of 99 smokers (12%) had fat necrosis compared with 3 of 112 nonsmokers (3%; p = 0.02). PMID- 8192382 TI - Preoperative lip taping in the cleft lip. AB - For the past 16 years, the senior author has used a nonsurgical method of mobilizing and approximating the soft tissues of the lip, nose, and maxilla before primary cleft lip repair. This has been accomplished effectively and inexpensively with the use of surgical tape applied to the lip across the cleft shortly after birth. The method used in applying the tape will be described. In addition to the positive soft-tissue effects, we found that lip taping effectively narrows, remodels, and approximates the alveolar arch, eliminating the need for initial orthodontia in all patients except those born with maxillary collapse. Lip taping accomplishes all of the goals of surgical lip adhesion at a fraction of the cost and eliminates the potential risk involved in one additional operation. PMID- 8192383 TI - The fate of fresh and preserved, noncrushed and crushed autogenous cartilage in the rabbit model. AB - This study was conducted to investigate volume retention and chondrocyte survival rate in autogenous fresh noncrushed, fresh crushed, preserved noncrushed, and preserved crushed cartilage grafts in rabbits. During the first phase of this investigation, cartilage was harvested from the right ear of 20 New Zealand white rabbits, then preserved. Four months later during the second phase, two 6-mm discs of previously harvested and preserved cartilage, one crushed and one noncrushed, were applied to the right ear. At the same time, two 6-mm discs of fresh cartilage graft were harvested from the left ear and then placed at a higher level on the same side, one crushed and one noncrushed. Three months after implantation, the rabbits were sacrificed and the grafts were evaluated. The preserved noncrushed cartilage retained 91.34% of the volume (SD = 2.46). Although most of the chondrocytes were nonviable, vascular ingrowth occurred with a significant repopulation of chondrocytes peripherally, in association with vascular endothelial ingrowth. The preserved crushed cartilage retained 74.19% of the volume (SD = 3.06). Most of the original chondrocytes were lost, but vascular ingrowth did occur and some osteoid formation occurred on the crushed cartilages. All chondrocytes on the fresh noncrushed cartilage grafts were viable and the grafts retained 94.54% of the volume (SD = 2.46). Crushed fresh cartilage retained 69.73% of its volume and the amount of viable chondrocytes ranged from 70% to 90% in the specimens evaluated (SD = 5.15). Although there is no question that noncrushed cartilage is superior, crushed cartilage can be used with a fair degree of predictability to attain the aesthetic goal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192384 TI - The role of preserved autogenous cartilage graft in septorhinoplasty. AB - Previous reports have established the role of fresh autogenous cartilage grafts harvested at the time of surgery. This report describes the value of autogenous preserved cartilage, removed and stored at the time of initial surgery, for use in secondary surgery. This study also compares fresh and preserved cartilage used in crushed and noncrushed states in secondary rhinoplasties. From 1983 to 1990, 256 of 1,185 patients who had undergone septorhinoplasty required a revision procedure. Cartilage graft was used in 186 (72.7%) patients. Cartilage removed during the primary surgery was stored in a saline and antibiotic solution at 0 degree F to 2 degrees F. The average time interval from primary to secondary surgery was 11.97 months (SD, 10.63 mo). Follow-up after graft placement averaged 44.71 months (SD, 26.21 mo). Two hundred seventy-seven pieces of cartilage were used, consisting of 16 noncrushed fresh, 136 crushed fresh, 8 noncrushed preserved, and 117 crushed preserved. Graft success rate was 93.8% for noncrushed fresh cartilage grafts, 87.5% for crushed fresh, 87.5% for noncrushed preserved, and 85.5% for crushed preserved graft. We conclude that preserved autogenous cartilage retains almost as much graft volume as fresh cartilage in rhinoplasties and eliminates the need for harvesting a graft. Cartilage removed during nasal surgery, particularly when a septoplasty is being performed, is valuable and should be stored for possible later use. PMID- 8192385 TI - Determination of the viability of crushed cartilage grafts: clinical implications for wound healing in nasal surgery. AB - Transplantation of uncrushed and crushed cartilage has assumed a role of great importance in reconstructive surgery of the nose. There are many divergent and contradictory opinions with regard to the outcome of cartilage, so we formulated this study to assess the functional state of chondrocytes in severely and mildly crushed as well as uncrushed and cut cartilage. Crushing and cutting leads to necrosis of a part of the graft. More of the cartilage cells are irreversibly damaged by crushing. The proportion of surviving cells, depending on the severity of crushing, is between 10 and 30%. In contrast to this, after cutting most of the cells remained viable and were able to proliferate. It is concluded that crushed cartilage not only remains unviable but is also not able to produce new cartilage; therefore, it will be subjected to resorption processes and not be useful for the reconstruction of parts of the nasal skeleton that support mechanical stress. PMID- 8192386 TI - A critical review of augmentation mammoplasty with saline-filled prostheses. AB - This report analyzes the results of augmentation mammoplasty using saline implants. Follow-ups ranged from 18 months to 13 years. Of the 75 patients in this review, 39 had one or more problems, after the initial surgery, that detracted from a good or excellent result. Forty-two patients needed different volumes of saline to balance asymmetry of the breasts. Fourteen patients who preoperatively were thought to have normal breasts had breast pathology shown by biopsy at the time of surgery. Sixty-seven of the 75 patients eventually had excellent or good results, but 22 patients needed more than the initial operation to achieve this. PMID- 8192387 TI - Biomechanical analysis of dorsal plate fixation in proximal phalangeal fractures. AB - The biomechanical properties of three minifragment plate and screw systems were compared to determine whether plate systems primarily designed for maxillofacial reconstruction are biomechanically sound for use in proximal phalangeal fracture fixation. A middiaphyseal transverse osteotomy was created in each of 30 fresh frozen human proximal phalanges to simulate an unstable fracture. Each osteotomy was then fixed with four 2.0ml screws through one of three different four-hole minifragment plates in a middorsal position. Plating systems tested included a vitallium plate with self-tapping screws (Luhr), a stainless steel plate with tapped screws (Synthes), and a titanium plate with tapped screws (Synthes). Testing was performed to failure in an apex volar three-point bending mode. The titanium-plated phalanges were the stiffest construct and required the greatest load and total energy absorbed to failure. However, only the load to failure for titanium versus stainless steel was significantly different. Therefore, there is no biomechanical disadvantage to using the titanium or vitallium plate and screw systems in the setting of unstable proximal phalangeal fractures. PMID- 8192388 TI - Modified split-level lid resection for blepharoptosis. AB - Mustarde's split-level lid resection surgery was popular through the 1980s for the correction of blepharoptosis with 7 mm or more of levator function. Although the aesthetic results gained with this technique were good, last line deformity and eyelid margin irregularities, such as central peaking at forward and upward gaze, were experienced. A simple modification of the tarsal resection pattern of Mustardes operation has solved these complications. In the treatment of 24 ptotic eyelids (12 unilateral, 6 bilateral with a modified split-level lid resection procedure), symmetrical appearance and level eyelids were obtained without lid margin peaking at 5 years' follow-up. The only persistent complication was lid lag at down-gaze in 10 eyelids. PMID- 8192389 TI - The use of pericranial flaps in frontal sinus fractures. AB - Although injuries to the frontal sinus are a reasonably common traumatic injury encountered by reconstructive surgeons, definitive indications for open exploration and the optimum method for handling the residual sinus cavity remain unsettled. During the last 3 years, we have accomplished frontal sinus obliteration with an "extended" pericranial flap in 14 consecutive patients. Thus far, we have not encountered any complications. PMID- 8192390 TI - Surgical treatment of posttraumatic enophthalmos: a study of 72 patients. AB - The present article deals with the surgical experience of treating 72 patients for posttraumatic enophthalmos. Patients were divided into the following 4 groups with respect to the type of injury and the time of surgery: Group 1, recent midfacial injuries with orbital floor fractures; Group 2, recent blow-out fractures; Group 3, neglected blow-out fractures; and Group 4, neglected fractures of the zygoma or the zygomatic-maxillary complex. Osteoplasty of the floor of the orbit was performed in all groups with bone or cartilage grafts such as lamina from the anterior maxillary wall, iliac and calvarial graft as well as rib cartilage. In addition to osteoplasty, reposition and fixation of fractured bones as well as refracture of malunited zygomatic-maxillary complex were performed in patients in Groups 1 and 4, respectively. Enophthalmos was recorded in 5 and 2 of 20 patients from Groups 1 and 2, respectively. In Group 3, enophthalmos was corrected in 3 of 7 patients, whereas 16 patients were corrected of 25 from Group 4. Advantages and disadvantages of applied surgical techniques are discussed and personal observations emphasized. PMID- 8192391 TI - The superficial temporal and retromandibular veins as guides to expose the facial nerve branches. AB - The superficial temporal vein and retromandibular vein were used as a guide to expose facial nerve branches in the parotid gland, and this procedure was applied to open reduction of mandibular condyle fractures (14 patients) and to superficial parotidectomy (6 patients). The advantages of this method are as follows: It is very easy to identify the superficial temporal vein as a guide, and it produces very little surgical stress because the procedure for exposing the facial nerve branches through the course of the vein is the same as the procedure for exposing the condyle and elevating the superficial lobe of the parotid gland. PMID- 8192392 TI - Ibuprofen treatment of ischemic musculocutaneous flaps. AB - The nonsteroidal antiinflammatory drug ibuprofen was tested as a potential agent in the pharmacological management of ischemia and reperfusion injury of swine flaps. After 6 hours of global ischemia, ibuprofen treatment was found to significantly improve the postischemic musculocutaneous flap survival. This was demonstrated by a dramatic 30.4 +/- 9.3% (p < or = 0.005) improvement in ischemic muscle survival, whereas the skin survival of ischemic musculocutaneous flaps was only moderately improved by 6.0 +/- 3.2% (p < or = 0.05). Thus, ibuprofen is potentially a powerful and effective treatment agent in the management of critically ischemic flaps and replants with high skeletal muscle content. PMID- 8192393 TI - Use of urokinase during secondary ischemia in experimental skin flaps. AB - The ability of urokinase to salvage experimental flaps after a secondary ischemic insult was investigated in a rat model. Unilateral abdominal island skin flaps based on the superficial inferior epigastric vessels were raised and subjected to either 4 or 6 hours of primary ischemia followed by 12 hours of reperfusion and varying lengths of secondary ischemia. At the conclusion of secondary ischemia, the flaps were perfused with either lactated Ringer's solution or urokinase. One group of flaps served as a control and received no postischemic perfusion washout. The secondary critical ischemia time at which 50% of the flaps failed clinically was greater for flaps perfused with urokinase. Furthermore, the survival rates for all flaps perfused with urokinase were significantly greater than either control flaps or flaps perfused with lactated Ringer's solution (p < 0.05). Flap survival decreased significantly in all groups with increasing primary and/or secondary ischemia time (p < 0.05). PMID- 8192394 TI - Time limits for intestinal ischemia and congestion: an experimental study in rats. AB - We investigated to determine the time limits for intestinal ischemia and congestion. The experimental models were produced by clamping both ends and the intended feeder vessels of an approximately 1-cm length of rat jejunum. The results showed that in arteriovenous occlusion, the time required for the recovery rate to reach 50% was 7.03 hours. The time required for the recovery rate to reach 50% was 6.81 hours when arterial occlusion alone was performed and 3.70 hours when venous occlusion alone was performed. The difference between the two was statistically significant (p < 0.01). Consequently, it was found that the degree of intestinal damage due to venous occlusion was greater than the damage resulting from arteriovenous and arterial occlusion. PMID- 8192395 TI - The inframammary island flap: anatomical basis. AB - The contribution of the thoracic internal artery to the breast's blood supply was studied in 24 fresh breasts. The second perforating artery was the largest in 20 breasts (86.3%). This artery supplies the upper portion of the breast, the nipple areolar complex, and the subjacent anteromedial region. On the basis of these anatomical findings, we propose a new cutaneous island flap raised from the redundant skin that is normally discarded in reduction mammoplasty. The use of this flap is indicated in breast and thoracic wall reconstruction. A clinical case of such reconstruction is reported. PMID- 8192396 TI - Extended anterior thigh flaps for repair of massive cervical defects involving pharyngoesophagus and skin: an introduction to the "mosaic" flap principle. AB - "Mosaic" flaps, i.e., connected anteromedial thigh-groin flaps, and connected anterolateral thigh-medial thigh flaps, the pedicles of which are the perforators of the lateral circumflex femoral system, the superficial circumflex iliac vessels, and the perforators from the femoral vessels are used to repair cervical skin defects involving the pharyngoesophagus. Although they appear to be similar to "siamese" flaps, these mosaic flaps are a new concept because they consist of two adjacent flaps that are simultaneously elevated with double pedicles including the lateral circumflex femoral system. The pedicles of the groin or the medial thigh flaps are anastomosed to the muscle branch or the descending branch of the lateral circumflex femoral system, which is the pedicle of the anterior thigh flaps, and the system is joined to a single recipient vessel as a "bridge" flap. The main advantages of these mosaic flaps are (1) they offer single recipient vessels, (2) they offer a larger extension of the vascular territory of a skin flap, and (3) they offer the possibility of creating custom-made composite flaps such as musculocutaneous and osteocutaneous flaps, and (4) the elevation of the flaps simultaneous with head and neck tumor resection is possible. Based on cited cases, it is suggested that mosaic flaps are suitable to use for reconstruction of massive cervical defects involving the cervical skin and the pharyngoesophagus due to recurrent laryngeal carcinomas. PMID- 8192397 TI - Sliding V-Y perineal island flaps for large perianal defects. AB - A large perianal defect resulting from resection of Bowen's disease was reconstructed with a pair of sliding V-Y perineal flaps. The anatomical basis of the flaps is described, based on the inferior rectal vessels as fasciocutaneous units. Both continence and sensibility are preserved with the procedure. PMID- 8192398 TI - Field of dreams. PMID- 8192399 TI - Re: The rat rectus abdominis myocutaneous flap: a true myocutaneous flap. PMID- 8192400 TI - European index to imaging literature. PMID- 8192401 TI - [Clinical anatomy for the use of surgeons of tomorrow]. PMID- 8192402 TI - [Diagnostic strategy of abdominal contusions in adults]. AB - Diagnosis of a deep visceral lesion in an adult following abdominal contusion is almost always difficult as the abdominal signs are late or masked by associated lesions. All of the controlled studies agree on the superiority of peritoneal puncture-lavage over ultrasonography or CT scan in the diagnosis of haemoperitoneum. The diagnostic performance of computed tomography in the identification of lesions of solid organs is very much better than that of ultrasonography. The diagnosis of an isolated lesion of a hollow viscus has benefited from progress in imaging to a much lesser degree and peritoneal puncture-lavage with leukocyte count remains the key examination. The diagnostic strategy must be based on the patient's clinical condition and on this hierarchy of complementary investigations. PMID- 8192403 TI - [Solitary ulcer of the rectum]. AB - In line with the literature, the authors consider that solitary ulcer of the rectum, either isolated, multiple or histological, like suspended proctitis, inverted hamartomatous polyp, deep cystic colitis, is a complication of rectal prolapse, which usually shares the same clinical symptoms. Solitary ulcer of the rectum is generally discovered on proctoscopy and is due to the strain exerted on the rectal mucosa by 2 opposing forces:violent effort of defecation against an anal and/or perineal obstruction. The reduction of these pressure and counterpressure forces with age and progressive alteration of the pelvic floor accounts for the progression of acute lesions towards chronic or attenuated lesions or even complete resolution. The therapeutic strategy should therefore decrease trauma by facilitating defecation by a combination of hygiene and dietary advice and biofeedback retraining, and surgical reduction of the anal obstruction and prolapse and correction of any perineal insufficiency. PMID- 8192404 TI - [Symposium on cancer of the pancreas]. PMID- 8192405 TI - [Surgical managements and cancer of the exocrine pancreas. Survey of the French Association of Surgery]. AB - In a French national enquiry, 3761 cases of cancer of the exocrine pancreas operated between 1982 and 1989 were collected. The aim of the part of the enquiry presented in this study was to define the various surgical attitudes. Surgical techniques significantly differed from one department to an another (P < 0.001). Resections were performed in 21 per cent of cases (range 6-45 per cent). Causes of unresectability, choice of a biliary by-pass, indications for gastro jejunostomy, and use of spanchnicectomy varied from one Surgical Department to another (P < 0.001). The magnitude of these differences can be explained only by different habits or skillfulness for a rarely curable disease. These findings would justify a consensus about the indications for various procedures in the treatment of cancer of the exocrine pancreas. PMID- 8192406 TI - [Treatments and prognostic factors of cancer of the pancreas based on the data of three cancer registries]. PMID- 8192407 TI - [Gastroesophageal reflux. Treatment by laparoscopy. 940 cases--French experience]. AB - In a French survey including 40 surgical teams, 940 patients with gastro oesophageal reflux were treated by laparoscopy (795: 85% by Nissen or Rossetti fundoplication; 90 by the Hill procedure. Conversion rate in to laparotomy was 6.2%. The rate of intra-operative complications was 5%. Overall mortality was 0.1% and post-operative morbidity also 5%. Oesophageal injuries (1.3%) remain the most important complication was especially in inexperienced surgeons in the beginning of training. Mean hospital stay was 5 days. Only one third of patients were reviewed controlled by endoscopy and/or mano-pHmetry with a 3-month follow up. Results are similar to those of "open" surgery. PMID- 8192408 TI - [Obstruction of the small intestine and celioscopic viscerolysis]. AB - The authors treated 16 patients with small bowel obstruction by 19 laparoscopy (3 patients underwent 2 laparoscopies). The operation was performed 4 times as an emergency and in 15 cases after resolution of the obstruction in patients who had already experienced such attacks. Adhesiolysis was complete in 14 cases and incomplete in 5 cases. Conversion in laparotomy was necessary in one patient to cure a total obstruction. 2 operative complications were reported (bowel perforation during enterolysis); one of which required conversion into laparotomy). This patient also developed post-operative complications whereas the post-operative course was uneventful for the other patients. Five patients developed an obstructive recurrence which required laparotomy in 2 cases and laparoscopy in the other 3 cases; but for two patients, initial enterolysis had been incomplete and a laparotomy was performed on another patient. Laparoscopic viscerolysis seems to be attractive but, the long-term outcome, and the frequency of adhesion recurrence need to be defined. PMID- 8192409 TI - [Osteosynthesis by tension band wiring of displaced fractures of the olecranon]. AB - Fifty-two displaced olecranon fractures in adults were treated over a 5-year period. Minimum follow-up was 6 months. Forty-eight fractures were operated and 38 were treated by tension band wiring technique. This technique, applied for all types of fractures, gave good functional results in 33 cases (87%) and fair functional results in 5 cases. Complications include 1 pseudarthrosis, 2 loss of reduction, 2 transient tourniquet palsy and 13 skin problems due to wire protrusion. Tension band wiring is a simple safe and effective technique for displaced olecranon fractures but often requires K-wire removal. PMID- 8192410 TI - [Treatment of deep anal fistulas using a flap from the rectal wall]. AB - Classic treatment of high anal fistulas by the laying open technique requires total or subtotal section of the sphincter muscles and results in anal incontinence. This study assesses the efficacy of the flap advancement technique in these cases. It entails the resection of the crypt at the origin of the fistula, the area being covered by a mucomuscular flap of the rectal wall. From 1977 to early 1992, 18 patients (13 female and 5 male patients; mean age: 40 years) presenting with a deep anal fistula underwent such an operation. There were 16 suprasphincteric and 2 high transsphincteric tracts. Associated IBD was noted in 7 cases (5 Crohn's colitis, 2 UC). Five fistulas were of obstetrical origin. In 8 cases, patients had undergone previous surgical treatments without success. All patients had a flap advancement. In 2 cases, a colostomy had been previously carried out. Two more diverting stomies were performed (combined abdominal procedures). No mortality or morbidity was encountered. Mean postoperative stay was 8 days. Current status could be established in all patients. Three immediate failures were observed (1 case of Crohn's disease, two recurring cases). All the other patients did well with persistent healing of the fistula after a mean follow-up of 61 months (range, 6-150). Three stomies were closed; one patient delayed the procedure. Functional results were excellent. In the "success" group, all the evaluable patients (14/15) had normal fecal continence. Two female patients are still complaining of mild flatus incontinence. In the failure group, the preoperative anorectal function was maintained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192411 TI - [Anorectal manometry and ileo-anal anastomosis: pre- and postoperative manometric comparison]. AB - The aim of this study was to evaluate the physiological and manometric changes of anorectal function after proctocolectomy and ileal J pouch anastomosis performed in 13 patients. A short muscular rectal cuff was conserved in the first 5 patients, mucosectomy was performed in the next patients (Group M), and the entire rectum and proximal portion of the anal canal (1 mm above the dentate line) were resected without mucosectomy (Group WM) in the most recent patients. With a median postoperative follow-up of 18 months, anorectal continence was perfect in 9 patients, and minimal incontinence were observed in 4 patients (2 patients in Group M, and 2 patients in Group SM). In Group M, the resting lower anal canal pressure was significantly decreased after the operation and was less than the postoperative resting lower anal canal pressure observed in Group SM. The resting upper anal canal pressure in continent patients was inferior to the postoperative values measured in patients with minimal incontinence. In all the groups, no change in squeeze pressure was observed after the operation. During the postoperative period, the rectoanal inhibitory reflex was absence in all patients. The volume necessary for sensation threshold was increased after the operation, in the same number of patients in Group M and SM, and more frequently in continent patients compared with patients with soiling. The absence of muscular rectal cuff and mucosectomy seems to provide best results than rectal cuff preservation. After the operation, a marked decrease in the resting pressure and an increase in the volume necessary to onset of threshold sensation, were associated with the presence of minimal incontinence. PMID- 8192412 TI - [Course of infection caused by human immunodeficiency virus]. AB - Following contamination with HIV, the majority of patients develop AIDS after several years (65% at 12 years), although a small percentage remain asymptomatic for a long time. The clinical manifestations of HIV infection are currently classified into 4 stages: primo-infection (stage I), asymptomatic phase (stage II), persistent generalised lymphadenopathy (stage III), other manifestations (stage IV), among which the following substages are distinguished: systemic signs (IVA), HIV-specific neurological signs (IVB), opportunistic or minor infections (IVA), HIV-specific neurological signs (IVB), opportunistic or minor infections (IVC), cancers (IVD) and other manifestations (IVE). The principal manifestations of AIDS appear when the CD4 count falls to below 200/mm3 and consist of opportunistic infections, primarily oesophageal candidiasis, pneumocystosis and toxoplasmosis. The management of patients with a combination of prophylaxis against opportunistic infections and antiviral treatment has significantly delayed the onset of AIDS, but has had little effect on the course of AIDS, which remains about 18 months. PMID- 8192413 TI - [Effect of fibrin glue on lymphostasis during lymph node excisions. Prospective randomized study in 40 patients]. AB - To evaluate the efficacy of fibrin glue for lymphostasis during axillary and inguinal lymph node removal, we conducted a prospective randomized study including 40 patients. Post-operative mortality and morbidity rates were not different throughout the 2 groups. However they were significant decreasement in drainage duration, in drainage quantity and in hospital duration in the group "with" fibrin when compared with the group "without". PMID- 8192414 TI - Routine determination of biliary lipid composition with the entero-test. AB - A simple method for the assay of biliary lipids was used for routine determination of biliary cholesterol saturation index (CSI) in 17 healthy subjects, 40 untreated patients with radiolucent gallstones and 21 gallstone patients treated with ursodiol. The method is based on collection of bile with the Entero-Test, a device for easy sampling of gastrointestinal contents. The procedure was easy to perform and well accepted by the patients. Both CSI and the cholesterol content of bile were higher in untreated gallstone patients than in controls, and were significantly lower in treated than in untreated patients. Normal CSI was found in 35% of untreated gallstone patients, while 24% of healthy subjects had supersaturated bile. Supersaturated bile was still present in 14% of ursodeoxycholic acid treated patients, suggesting inefficacy of therapy. These results demonstrate the possibility of performing easy, routine determination of biliary lipid composition, which can yield useful information for the management of gallstone patients. PMID- 8192415 TI - [Intraluminal polyp of the common bile duct corresponding to a metastasis of cancer of the kidney]. AB - The authors report the second case to date of metastatic carcinoma of the common bile-duct from renal cell cancer presenting as an intraluminal polypoid mass. Obstructive jaundice developed in a 55-year old woman 14 years after nephrectomy for renal cell carcinoma. The diagnosis of polypoid tumor of the common bile-duct was established by sonography, endoscopic retrograde cholangiopancreatography and CT-scan. Palliative resection was performed. Postoperative histological examination revealed the resected tumor to be identical to the clear cell type of renal cell carcinoma. The postoperative course was marked by the development of distant metastases 6 months later. Diagnosis and therapeutic features of metastatic malignant biliary obstruction are discussed. PMID- 8192416 TI - [Malignant pheochromocytoma of the adrenal gland. Diagnosis 14 years after an incidental discovery of a contralateral pheochromocytoma]. AB - The authors present a case of malignant adrenal phaeochromocytoma incidentally discovered 14 years after a similar finding in the controlateral adrenal gland. The rarity of incidentally discovered malignant adrenal phaeochromocytoma (second report in the literature) and the importance of isotope scan with MIGB for the investigation of asymptomatic and nonfunctioning phaeochromocytomas are outlined. PMID- 8192417 TI - [Iatrogenic aneurysm of the hepatic artery. Treatment by percutaneous injection of thrombin and selective arterial embolization]. AB - One case of hemobilia, revealing a right hepatic aneurysm, following a hepatic biopsy for active chronic hepatitis B, is reported. The diagnosis established by computed tomography and arteriography. Because of chronic hepatitis and the high localization of the aneurysm, surgery was not performed. A direct percutaneous thrombin injection was performed, owing to the fact that arterial catheterization was unsuccessful, and was followed by a decrease in volume of the aneurysm, but definitive recovery was achieved secondarily by arterial embolization (coil). This case illustrates the therapeutic alternative biopsy in intrahepatic arterial aneurysm treatment. PMID- 8192418 TI - [Endoscopic hemostasis of hemorrhagic gastroduodenal ulcers]. AB - The mortality rate for peptic ulcer bleeding has remained constant for several decades, despite advances in surgery and intensive care, and this has given rise to an interest in therapeutic hemostatic endoscopy. Thus, endoscopy in the treatment of peptic ulcer hemorrhage would be undertaken with the aim of obtaining an early and precise diagnosis of the hemorrhagic lesions, to arrest active bleeding and/or to prevent rebleeding. In the selection of patients justifying an endoscopic hemostatic treatment, intervene clinical criteria (age, concomitant pathologies, current medication, hemodynamic parameters), endoscopic criteria (active arterial bleeding, visible vessels). The most frequently employed methods are laser photocoagulation, thermal probe cauterization, electrocoagulation and sclerotherapy. None of these methods have gained supremacy. There is consensus that sclerotherapy should be the method of reference (simple and inexpensive). Endoscopic methods are capable of arresting bleeding and constitute an alternative method to surgery in cases of emergency. They should reduce recurrence of hemorrhages, but nevertheless have no influence on the prognostic parameters which are essentially clinical. PMID- 8192419 TI - [Hepatic angiomyolipoma. 2 case reports and review of the literature]. AB - We report two cases of hepatic angiomyolipoma. The first tumor was disclosed at the time of resection of a cardia carcinoma, and temporarily regarded as a possible metastasis. The second tumor was an enormous necrotic mass of the right liver in a young woman mimicking a sarcoma. PMID- 8192420 TI - [Chronic diarrhea during treatment with Veinotonyl 75]. PMID- 8192421 TI - [Severe digestive manifestations of rheumatoid purpura in adults]. AB - The authors report three cases of Scholein-Henoch's purpura in adults which were characterized by atypical severity of the digestive signs which led to laparotomy. In one case, the digestive signs preceded the onset of the cutaneous purpura, which made the diagnosis difficult. The digestive impact was confirmed endoscopically (petechia, ulceration, ulcerated stenosis) in two of the three patients. Damage of the small intestine predominated, as in the literature, but only one patient required resection of the intestine. These observations highlight the importance of endoscopic exploration in cases of abdominal signs combined with Scholein-Henoch's purpura in adults. They also demonstrate the difficulty of evaluating the prognosis and treatment in severe, peritoneo occlusive forms. PMID- 8192423 TI - Measures of body mass and of obesity from infancy to adulthood and their appropriate transformation. AB - In this paper we investigate first the choice of an appropriate index of body mass. The traditional indices weight/height (W/H), W/H2 and W/H3 are compared, as well as an approach due to Cole (1986) making the index W/Hp age-dependent, i.e. by allowing the power p to depend on age. While there may be no perfect index reflecting over- and underweight--irrespective of height and width--the Quetelet index W/H2 turned out to be a reasonable index from childhood to adulthood. Second, we study the development of the body mass index W/H2 longitudinally from birth onwards, based on structural average distance, velocity and acceleration curves. As a third topic, transformations for obtaining an approximate normal distribution for W/H2, weight and skinfolds are compared. The usual log transformation turned out to be unsatisfactory. While for height and arm skinfolds a transformation -1/square root of x performs rather well across age and sex, a transformation -1/x is more appropriate for trunk skinfolds and W/H2. PMID- 8192422 TI - [Tuberculous anal fistulas. 13 cases]. AB - Our retrospective study concerns 13 cases of anal tuberculosis fistulas, studied over a period of 12 years, between January 1980 and December 1991. The mean age of our patients was 24 years and they were predominantly male. The diagnosis, which was suspected clinically, was confirmed histologically, either by ridge biopsies of the external orifice of the fistula or by surgical removal of the fistular passage in patients having undergone an initial surgical intervention. In 5 cases, we noted an associated pulmonary tuberculosis involvement. The treatment comprised 2 phases: an antibacillary medical treatment in all cases and a surgical treatment depending on whether the diagnosis was initially based on the ridge biopsies of the external orifice--6 cases (46.15%)--or after removal of the fistular passage--7 cases (53.85%). The outcome was good in all cases. PMID- 8192424 TI - Genetic structure of a tribal population: anthropometric differences between regions and settlements among the Yanadi. AB - Microevolutionary changes in morphology were investigated in a transient tribal population who are fast changing from a hunting-gathering to an agricultural stage. Anthropometric data on 14 measurements collected from the Yanadi, who inhabit different geographical regions and differ in their subsistence and other associated cultural traits, demonstrate high morphologic differentiation between two levels of organization: (1) 12 settlements and (2) five regional breeding populations formed by grouping some of the former. The morphologic distances based on Mahalanobis D2 and the dendrograms show wide differences between sexes, in the case of the breeding populations, which can be associated with patterns of marital migration and of spatial distances. In the case of settlements the pattern shows a poor association with geography. Of three spatial distances viz. map, road and geographical barrier index, road distance produces a larger influence on the morphological differentiation within the tribe. PMID- 8192425 TI - The importance of socioeconomic and nutritional conditions rather than altitude on the physical growth of prepubertal Andean highland boys. AB - The aim of this work was to study the effect of hypoxic stress on the physical growth of prepubertal Bolivian boys (10-11.5 years of age) of the same socioeconomic and nutritional conditions. The subjects consisted of 143 boys living in La Paz (altitude 3600 m, n = 67) and Santa Cruz de la Sierra (altitude 420 m, n = 76). Among the boys studied at high altitude, 23 were from a high socioeconomic background (HA1) and 44 from a low socioeconomic background (HA2). The group studied at low altitude consisted of 47 boys from a high socioeconomic background (LA1) and 29 from a low socioeconomic background (LA2). A scientific evaluation of the nutritional status of the boys was realized from specific anthropometric characteristics (height, body weight, upper arm muscle circumference, body fat mass and body mass index) and haematological (haematocrit, haemoglobin, serum iron, serum ferritin, red cell protoporphyrin, transferrin saturation) and biochemical (total serum protein, albumin and prealbumin) parameters. At high as at low altitudes, the biometric characteristics of boys from a low socioeconomic background were significantly lower than those of boys from a high socioeconomic background. The physical growth of HA2 and LA2 boys was delayed by approximately 2 years. All the boys had biochemical and haematological parameters within the normal range. Boys from a low socioeconomic background were considered as marginally undernourished and those from a high socioeconomic background as well-nourished. Within the same socioeconomic class there was no nutritional difference between highland and lowland boys. Similarly, and this is the most important feature of this study, there was no difference for the overall biometric characteristics between highland and lowland boys of the same socioeconomic and nutritional status. Therefore, it appears that when socioeconomic and nutritional conditions are taken into account, there is no effect of hypoxic stress on the physical growth of prepubertal Andean highland boys. PMID- 8192426 TI - Geographical and ethnic variability of finger ridge-counts: biplots of male and female Indian samples. AB - The graphical technique of biplot due to Gabriel and others is explained, and is applied to ten finger ridge-count means of 239 populations, mostly Indian. The biplots, together with concentration ellipses based on them, are used to study geographical, gender and ethnic/social group variability, to compare Indian populations with other populations and to study relations between individual counts and populations. The correlation structure of ridge-counts exhibits a tripartite division of digits demonstrated by many other studies, but with a somewhat different combination of digits. Comparisons are also made with the results of Leguebe and Vrydagh, who used principal components, discriminant functions, Andrews functions, etc., to study geographical and gender variations. There is a great deal of homogeneity in Indian populations when compared to populations from the rest of the world. Although broad geographical contiguity is reflected in the biplots, local (states within India) level contiguity is not maintained. Monogoloids and Caucasoids have distinct ridge-count structures. The higher level of homogeneity in females and on the left side observed by Leguebe and Vrydagh is also observed in the biplots. A comparison with principal component plots indicates that biplots yield a graphical representation similar to component plots, and convey more information than component plots. PMID- 8192427 TI - Stature loss from sustained gentle body loading. AB - The effects of low levels of loading on spinal creep have been investigated in nine young men aged between 19 and 24 years. The stimulus for the project was an interest in the potential use of stadiometry in evaluating selected classes of patients with spinal disorders. Underlying the experiment was the view that if gentle spinal loadings cannot be differentiated sensitively in normal young adults then the feasibility of using stadiometric measurements to identify patients with decreased lability is questionable. Subjects were measured on a precision stadiometer before and after 25 minutes of free standing and quiet walking, and the resultant stature losses compared with the more substantial losses observed following steady running. All measurements were made following the same presession routine, at exactly the same time on three separate mornings. It was observed that while no appreciable stature loss followed standing (mean = 0.01 mm; SE = 0.65 mm; p > 0.05) even quiet walking had a measurable and statistically significant effect (mean = 1.82 mm; SE = 0.49 mm; p < 0.01). Compared with these, steady running produced almost 2 1/2 times as great a loss (mean = 4.32 mm; SE = 0.83 mm; p < 0.01). It is concluded: (a) that erect standing provides a useful neutral baseline from which the changes associated with spinal loading and unloading may be measured; (b) that the effects of even gentle spinal loadings may be differentiated sensitively by precision stadiometry; and (c) that easy walking is one such gentle stimulus with detectable effects in normal young men. PMID- 8192428 TI - A decline and a halt in mean age at menarche in Iceland. AB - Mean age at menarche has been declining in many countries during the past hundred years. Reports of a halt in this trend have come from Oslo and London. In this study the trend in age at menarche in successive birth cohorts, starting in 1900, was investigated for the first time in Iceland. This was based on recall data obtained as part of a cervical cancer screening programme covering the whole country. Around 78% of the female population at the ages targeted for screening responded to questions on reproductive factors in the years 1964-89, or over 73,000 women aged 20-69 years. Investigation of the validity and reliability indicated that the estimated mean age is likely to be unbiased, and that for 90% of the women the information was reliable. Mean age at menarche declined from 14.9 years to 13.5 years in successive cohorts of Icelandic women born 1900 to around 1950. In cohorts born 1951-67 the mean age has remained stable. The halt appeared later than reported from Oslo and London and at a higher age. PMID- 8192429 TI - Trend in menarcheal age and socioeconomic influence in Bologna (northern Italy). AB - Temporal variations in menarcheal age in the Bologna province (northern Italy) were investigated in a sample of 2930 women born between 1930 and 1973, examined by retrospective method. A decrease in mean menarcheal age between birth decades 1930-39 and 1950-59 was noticed. The trend was more intense in lower social classes living in extra-urban environments. This led to a disappearance in menarcheal age differences between city and province and between socioprofessional categories. From birth decade 1950-59 onwards an increase in menarcheal age is registered, and an influence of physical activity and family structure on the age of menstrual cycle onset is observed. Our results suggest that the secular trend towards earlier age at menarche has stopped in the Bologna area. We hypothesize that the recent delay in puberty could be a response to an increase in physical and psychosocial stress. PMID- 8192430 TI - [Distribution of ABO allele frequencies in the Dusseldorf regional district (Northern Rhine-Westphalia)]. AB - The AB0 allele frequencies and their regional distribution have been studied in the administrative area of Dusseldorf, North Rhine-Westphalia. The o allele shows relatively low and the B allele relatively high frequencies in the eastern and south-eastern parts of the region. The high B frequencies are interpreted as a consequence of the immigration from north-eastern Germany and Poland at the end of the 19th and the beginning of the 20th century (labourers) and after 1945. PMID- 8192431 TI - Glyoxalase-I (GLO) polymorphism among two endogamous populations of Andhra Pradesh, India. AB - Glyoxalase-I phenotypes have been screened electrophoretically in the Kotia and Relli populations of the Visakhaptnam District, Andhra Pradesh (India). The GLO*1 allele varies from 0.2560 in the Kotia to 0.3258 in the Relli, which is well within the range of South Indian populations. PMID- 8192432 TI - Genetic studies in some ethnic groups of Pakistan (Southern Punjab): colour blindness, ear lobe attachment and behavioural traits. AB - Frequency distributions of colour blindness, adherent ear lobe, hand clasping, arm folding and leg folding are reported for different ethnic groups (Balochs, Rajputs, Syeds, Pathans, Araeen and Jats) for Pakistan (Southern Punjab). The F analysis suggests an insignificant difference between these groups, though the LSD value indicates a significant difference of Balochs with the other groups. The association Chi-square values suggest the independence of the three behavioural traits. PMID- 8192433 TI - Radiopaque transverse lines (Harris lines) in the prehispanic population of El Hierro (Canary Islands). AB - Harris lines were assessed in 48 right tibiae of prehispanic inhabitants of El Hierro (one of the Canary Islands), belonging to 23 adult females and 25 adult males. No Harris lines were detected in sixteen (33%) of the adult individuals (7 females = 30% and 9 males = 36%), these differences are not statistically significant. Female tibiae showed a slightly higher mean number of Harris lines at the distal end than male ones (2.091 +/- 1.9 in females vs 1.417 +/- in males). Ages at which Harris lines were formed show two peaks, a major one at the age of 2 years, and another one between 11 and 13, particularly in the females. Harris lines were more frequently observed at the proximal than at the distal end of the bone. No relation was found between the number of Harris lines and stature. The relative high number of lines detected in our population speak for several stressful episodes suffered during growth. PMID- 8192434 TI - Study of finger and palmar dermatoglyphics in primary infertile males. AB - Finger and palmar dermatoglyphic variations have been studied in 160 diagnosed primary infertile males (111 clinically abnormal primary infertile males and 49 clinically normal primary infertile males). It has been observed that loops occur most frequently in primary infertile males. Arches are found to be absent on digit IV and V. Among the clinically normal infertile males the mainline formula 7.5.5--succeeds 11.9.7--instead of 9.7.5--in the order of preponderance. Bilateral and inter-group differences among clinically abnormal and normal infertile males have been found to be statistically non-significant for finger and palmar comparison. The present findings are compared with the result on finger and palmar dermatoglyphics of controls (130 Punjabi males of Delhi). Clinically normal infertile males show statistically significant differences in the occurrence of various pattern types of finger balls when compared with controls. Similarly, clinically abnormal as well as normal primary infertile males reveal statistically significant results in the occurrence of patterns in the hypothenar and Thenar/I interdigital area of palms when compared with controls. PMID- 8192435 TI - [Androcentric attitude in anthropology: examples from research of the evolution of man]. AB - While feminist anthropology already gained a certain tradition in the USA, there are almost no corresponding approaches in the German-speaking sphere. Comparing male viewpoints, which still prevail in science, with female perspectives reveals that a male bias frequently caused misinterpretation, especially in the field of human evolution. Using the topics hunter/gatherer, concealment of ovulation, and mating systems as examples, male and female perspectives are compared. These examples reveal the existence of differences between male and female points of view, and they show how female perspectives complement scientific findings and improve the precision of descriptions. Therefore interpretations from a female point of view should increasingly be considered, in order to gain further insights and improve the formation of hypotheses in the field of human evolution and behavior. PMID- 8192436 TI - New quinolones and gram-positive bacteria. PMID- 8192437 TI - In vivo activity of paromomycin against susceptible and multidrug-resistant Mycobacterium tuberculosis and M. avium complex strains. AB - Encouraged by in vitro results, we have assessed the in vivo activity of paromomycin (PRM) against Mycobacterium tuberculosis, multidrug-resistant (MDR) M. tuberculosis (resistant to isoniazid, rifampin, and streptomycin), and Mycobacterium avium complex in C57BL/6 mice and their beige counterparts. In all these experiments, PRM was effective in preventing mortality from a mycobacterial infection and was significantly more active than the drug-free control (P < 0.0005) in reducing the CFU relative to the mean log CFU in the lungs, livers, and spleens of infected animals. In the drug-susceptible M. tuberculosis experiment, PRM given at 100 and 200 mg/kg of body weight was significantly less active than isoniazid at 25 mg/kg (P < 0.0005) in reducing the mean log CFU in the lungs, livers, and spleens of infected mice. In the MDR M. tuberculosis experiment, PRM given at 200 mg/kg was effective, relative to the drug-free control, in reducing the mean log CFU of an isolate of M. tuberculosis resistant to isoniazid, rifampin, and streptomycin. In the M. avium complex experiment, PRM given at 200 mg/kg was as effective as amikacin at 50 mg/kg in reducing the mean log CFU in the lungs, livers, and spleens of infected mice. On the basis of our experiments, we believe that PRM has promising activity in vivo in the treatment of infections caused by M. tuberculosis, MDR M. tuberculosis, and M. avium complex. PMID- 8192438 TI - A randomized, double-blind, comparative trial comparing high- and standard-dose oral acyclovir for first-episode genital herpes infections. AB - Orally administered acyclovir ameliorates the clinical course and decreases the duration of viral shedding in patients with first-episode genital herpes infections. We investigated in a randomized, double-blind, comparative trial whether a higher (4 g) than standard (1 g) daily dose of oral acyclovir results in greater clinical benefit and influences the time to first recurrence. A total of 139 patients with first-episode genital herpes were randomized to receive orally 4 or 1 g of acyclovir daily. A total of 52 subjects were excluded from the efficacy analysis because most had recurrent disease. Of 87 eligible subjects, 28 (32%) had primary herpes simplex virus type 1 (HSV-1) infections, 48 (55%) had primary HSV-2 infections, and 11 (13%) had nonprimary HSV-2 infections. We did not find any statistically significant differences in the duration of symptoms or viral shedding between the two dose groups, nor did the median time to first recurrence differ between the two groups. Initiation of therapy with either dose within the first 3 days of the appearance of symptoms shortened the duration of the first episode. Adverse gastrointestinal effects developed in 8% of subjects receiving the higher dose, whereas no adverse reactions were observed among those receiving the standard dose (P = 0.10). We conclude that, in comparison with standard therapy, higher-dose oral acyclovir does not result in additional clinical benefit or modify the time to first recurrence. The present study may have implications for the development and efficacy of congeners of acyclovir which provide higher levels in blood than the standard dose of acyclovir. PMID- 8192439 TI - In vitro renal toxicity and in vivo therapeutic efficacy in experimental murine cryptococcosis of amphotericin B (Fungizone) associated with Intralipid. AB - We compared the experimental toxicities and activities of deoxycholate amphotericin B (d-AmB) dissolved in glucose (Dd-AmB) or mixed with 20% Intralipid (ILd-AmB). In vitro, ILd-AmB against renal tubular cells in primary culture. In vivo, the toxicities and activities of Dd-AmB and ILd-AmB were studied in DBA2 mice with cryptococcosis. The maximum tolerated dose of intravenously administered d-AmB, i.e., the dose that induced less than 15% mortality because of toxicity, was 1.7 to 2.5 times higher when it was administered as ILd-AmB than when it was administered as Dd-AmB. Both treatments given intravenously at the same dose were equivalent for improving the survival of mice and reducing CFU counts in infected tissue, but at maximum tolerated doses, ILd-AmB (2 mg/kg of body weight) was more effective than Dd-AmB (0.8 to 1.2 mg/kg). AmB concentrations in spleen, liver, lung, and kidney were measured by high-pressure liquid chromatography 4 and 24 h after a single injection of 1.2 mg of Dd-AmB per kg, 1.2 mg of ILd-AmB per kg, or 2 mg of ILd-AmB per kg. In a given organ, AmB levels were similar after administration of 1.2 mg of Dd-AmB or ILd-AmB per kg but were significantly higher after administration of 2 mg of ILd-AmB per kg. The lower level of toxicity of ILd-AmB might be explained by circular dichroism experiments, showing that ILd-AmB contained 10-fold less soluble oligomeric AmB, which is believed to be the toxic form of the drug, than Dd-AmB. We conclude that ILd-AmB is as efficient as Dd-AmB and is better tolerated than Dd-AmB in mice with experimental cryptococcosis. By allowing higher doses of AmB to be infused, Intralipid enhances AmB concentrations in infected sites, and thus the therapeutic activity of the drug. PMID- 8192440 TI - Use of multivariate analysis to compare antimicrobial agents on the basis of in vitro activity data. AB - Multivariate techniques such as principal component analysis or similar factor analysis help in analyses of the simultaneous interrelationships among several variables. A comparative multivariate analysis on the in vitro activities of eight antimicrobial agents, including the novel molecule daptomycin, is presented. Multivariate analysis detects components or factors and establishes connections among antimicrobial agents on the basis of their different levels of participation in each factor. The first principal component was dominated by vancomycin, teicoplanin, and rifampin (0.94344, 0.92792, and 0.72127, respectively). The second principal component showed strong effects from imipenem, gentamicin, and cephalothin (0.87922, 0.86126, and 0.68870, respectively). Daptomycin stood out alone in the third principal component (0.83983). The first three components defined 81.5% of the total variance and could easily be represented graphically in a three-dimensional scatter plot. In this graphic representation, the eight antimicrobial agents clustered in three different spatial regions; daptomycin occupied a separate spatial position. The use of multivariate analysis offers a different approach to determination of the in vitro activities of new antimicrobial agents and adds some new data on the relationships among different classes. Notwithstanding its limitations, the application of these methods in microbiology and drug development could be an additional tool for use in processing information. PMID- 8192441 TI - Subcellular distribution of daptomycin given alone or with tobramycin in renal proximal tubular cells. AB - Previous studies in experimental animals showed that daptomycin, a lipopeptide antibiotic, protects against aminoglycoside nephrotoxicity (C. A. Wood, H. C. Finkbeiner, S. J. Kohlhepp, P. W. Kohnen, and D. N. Gilbert, Antimicrob. Agents Chemother. 33:1280-1285, 1989; D. Beauchamp, M. Pellerin, P. Gourde, M. Pettigrew, and M. G. Bergeron, Antimicrob. Agents Chemother. 34:139-147, 1990). In order to better understand the mechanism involved in this protective effect, the subcellular distribution of daptomycin was investigated in the proximal tubular cells of animals treated with daptomycin alone or in combination with tobramycin. A first group of female Sprague-Dawley rats received a single intravenous injection of daptomycin at a dose of 100 mg/kg of body weight and were killed at 10 min, 1 h, or 24 h after the injection. Other groups of rats were treated during 10 days with saline (NaCl, 0.9%), tobramycin at dosages of 20 mg/kg/12 h, daptomycin at dosages of 10 mg/kg/12 h, or the combination tobramycin daptomycin at the same dosages. At the time of sacrifice, the renal cortex of the right kidney of each animal was dissected, and small blocks of tissue were fixed, dehydrated, and embedded in Araldite 502 epoxy resin. The subcellular distribution of daptomycin and tobramycin was determined on ultrathin sections by immunogold labeling. Ten minutes after the injection of daptomycin alone, gold particles were seen over the brush border membrane and on the membranes of the endocytic vacuoles of proximal tubular cells. One hour after the injection, a similar distribution was seen and numerous gold particles were found over the lysosomes of proximal tubular cells. The results suggest that daptomycin might protect against aminoglycoside nephrotoxicity by interfering with the interaction between the aminoglycoside and phospholipids inside the lysosomes of proximal tubular cells. PMID- 8192442 TI - Different ratios of the piperacillin-tazobactam combination for treatment of experimental meningitis due to Klebsiella pneumoniae producing the TEM-3 extended spectrum beta-lactamase. AB - We evaluated the pharmacokinetics and therapeutic efficacies of piperacillin and tazobactam, a beta-lactamase inhibitor, given either alone or in different combinations (80:10, 200:10, and 80:25 mg/kg/h), in experimental meningitis due to a strain of Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta lactamase. Treatment was administered intravenously as a 7-h constant infusion preceded by a bolus of 20% of the total dose. The mean (+/- standard deviation) rates of penetration into the cerebrospinal fluid (CSF) of infected animals were 6.7 +/- 3.9% for piperacillin given alone and 36.3 +/- 21.9% for tazobactam given alone. Combination treatment significantly magnified the concentration of either drug in CSF. Concentrations of bacteria in CSF increased throughout therapy in animals given either drug alone, even at high dosages. In animals given the combination at dosages of 80:10 and 200/10 mg/kg/h, only a suboptimal reduction of CSF bacterial titers was obtained in vivo, i.e. -0.49 +/- 0.34 and -0.73 +/- 0.49 log CFU/ml/h, respectively. An increase in the tazobactam dosage within the combination (80:25 mg/kg/h) was required in order to obtain a significantly faster elimination of viable organisms from the CSF (-0.97 +/- 0.35 log CFU/ml/h). The study shows that tazobactam is able to provide effective protection against piperacillin hydrolysis by the TEM-3 enzyme within the CSF. Appropriate dosage regimens of various beta-lactam-tazobactam combinations may deserve comparative studies in experimental meningitis caused by organisms producing extended-spectrum beta-lactamases. PMID- 8192443 TI - In vitro extracellular and intracellular activities of clavulanic acid and those of piperacillin and ceftriaxone alone and in combination with tazobactam against clinical isolates of Legionella species. AB - The activities of ceftriaxone, piperacillin, tazobactam, clavulanic acid, and combinations of ceftriaxone or piperacillin with tazobactam against 22 clinical Legionella isolates were measured by broth microdilution and macrodilution methods and in macrophages. The broth microdilution MICs that inhibited 90% of strains tested were 2 and 1 microgram/ml for ceftriaxone and tazobactam, respectively. Broth macrodilution MICs were 8 and 1 microgram/ml, respectively, for the two Legionella pneumophila strains tested with piperacillin and were 0.25 and 0.5 microgram/ml, respectively, for clavulanate. No significant intracellular anti-L. pneumophila activity was observed for ceftriaxone (32 micrograms/ml), piperacillin (32 micrograms/ml), tazobactam alone (16 micrograms/ml), clavulanate alone (2 micrograms/ml), or tazobactam in combination with ceftriaxone (ceftriaxone/tazobactam at 32/4 and 16/16 micrograms/ml) or piperacillin (32/4 micrograms/ml). Erythromycin (1 microgram/ml) was active against intracellular L. pneumophila in the same macrophage model of infection. It is very unlikely that tazobactam or clavulanate, alone or in combination with beta-lactam antimicrobial agents, will be effective for the treatment of Legionnaires' disease in humans. PMID- 8192444 TI - Penicillin-binding proteins are regulated by rpoS during transitions in growth states of Escherichia coli. AB - Attention has been recently focused on the role of the rpoS (formerly katF) gene product as a regulator during the transition from the exponential growth phase to the stationary phase as well as during nutritional starvation. It has been demonstrated that RpoS is an alternate sigma factor which would bind to promoters of genes induced at these times. It was previously noted that rpoS mutants do not undergo a transition to short rods during entry into the stationary phase. Because of their well-established role in morphogenesis, we investigated the status of the penicillin-binding proteins (PBPs) in Escherichia coli wild-type and isogenic rpoS mutants. Samples from cultures of E. coli ZK126 and ZK1000 (rpoS::kan) were taken in the midlogarithmic, early stationary, and late (24 h) stationary phases. The increase in PBP 6 seen upon entry of the wild-type strain into the stationary phase was not observed with the rpoS::kan cells, even after 24 h. There was also a marked decrease of PBP 3 in wild-type stationary-phase cells; PBP 3 has a known influence on morphogenesis. This decrease in PBP 3 was found to be markedly affected by the disruption of rpoS. Similar observations were made after prolonged starvation of the two strains for either glucose or a required amino acid. Inasmuch as PBPs are involved in peptidoglycan synthesis, we also examined two properties of peptidoglycan, autolysis and cross-linkage, that might be altered by the PBP differences. However, neither of these properties, which are known to undergo changes in the stationary phase, appeared to be influenced by the status of RpoS. PMID- 8192445 TI - Effect of CO2 on susceptibilities of anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin. AB - The Oxyrase agar dilution method (Oxyrase, Inc., Mansfield, Ohio), which provides an anaerobic environment without added CO2, was compared with the reference agar dilution method recommended by the National Committee for Clinical Laboratory Standards (anaerobic chamber with 10% CO2) to test the susceptibilities of 302 gram-negative and gram-positive anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin. For erythromycin, the overall MIC for 50% of isolates tested (MIC50) was 0.5 micrograms/ml and the MIC90 was 8.0 micrograms/ml by the Oxyrase method, whereas they were 4.0 and 64.0 micrograms/ml, respectively, under standard anaerobic conditions with CO2. At a breakpoint of 4.0 micrograms/ml, 88% of strains were susceptible to erythromycin by the Oxyrase method, whereas 63% were susceptible in the chamber. The corresponding MIC50s and MIC90s of azithromycin, clarithromycin, and roxithromycin by the Oxyrase method were 0.5 and 8.0, 0.25 and 4.0, and 0.5 and 16.0 micrograms/ml, respectively, whereas in the chamber they were 4.0 and > 64.0, 2.0 and 64.0, and 2.0 and 64.0 micrograms/ml, respectively. At a breakpoint of 8.0 micrograms/ml for these three drugs, 89, 92, and 85% of the isolates, respectively, were susceptible by the Oxyrase method, whereas 67%, 72, and 68% of the isolates, respectively, were susceptible in the chamber. Most strains resistant to all four compounds by both methods were Bacteroides distasonis, Fusobacterium mortiferum, Fusobacterium varium and non-Clostridium perfringens Clostridium species. Results of the study may lead to a reappraisal of the role played by macrolides and azalides in the treatment of anaerobic infections. PMID- 8192446 TI - Azithromycin pharmacokinetics and intracellular concentrations in Legionella pneumophila-infected and uninfected guinea pigs and their alveolar macrophages. AB - Azithromycin pharmacokinetics in Legionella pneumophila-infected and uninfected guinea pigs were assessed by measuring the drug concentration in whole lungs or the drug content in bronchoalveolar lavage (BAL) fluid in separate experiments. Azithromycin concentrations were measured by using a bioassay. The mean azithromycin content in the BAL fluid of infected guinea pigs was higher than that in controls at 10 h (0.87 versus 0.39 microgram; P = 0.05), 24 h (1.10 versus 0.37 microgram; P = 0.003), and 48 h (1.21 versus 0.28 microgram; P = 0.05) after a single intraperitoneal injection of drug (15 mg/kg). The mean peak lung azithromycin concentration was higher in control animals than in infected animals (15.8 versus 13.4 micrograms/ml). The mean lung azithromycin concentration in infected animals was significantly higher than that in controls 48 h after dosing (12.7 versus 10.4 micrograms/g; P = 0.04). There were no significant differences between infected and uninfected animals in serum azithromycin levels. Complementary experiments assessed intracellular/extracellular concentration ratios of azithromycin and erythromycin in L. pneumophila-infected and control guinea pig alveolar macrophages. Azithromycin was highly concentrated in alveolar macrophages, and the intracellular/extracellular concentration ratios for infected cells were significantly higher (P < 0.0001) than those observed in controls after 4 h (127 versus 119), 24 h (481 versus 361), and 48 h (582 versus 520) of incubation. Erythromycin was also preferentially concentrated in infected cells (P < 0.0001). AZ intracellular concentrations were at least fivefold higher than those measured for erythromycin, and this differential increased with incubation time. Thus, azithromycin recovery from BAL fluid, and from guinea pig lungs at the 48-h time point, was higher in the presence of experimental Legionnaires' disease. This likely results from recruitment of phagocytes, including macrophages, that have an enhanced capacity to highly concentrate the drug. PMID- 8192447 TI - Influence of lipoproteins on renal cytotoxicity and antifungal activity of amphotericin B. AB - We examined the influence of high-density lipoproteins (HDLs) and low-density lipoproteins (LDLs) on the toxicity of amphotericin B (AmpB) to fungal and renal cells. Candida albicans was incubated for 18 h at 37 degrees C with AmpB and deoxycholate (Fungizone) or liposomal AmpB (L-AmpB) (0.1 to 2.0 micrograms of AmpB per ml) in the presence or absence of HDLs or LDLs (0.5 mg of protein per ml). The MICs of AmpB and L-AmpB, whether or not HDLs or LDLs were present, were similar. LLC PK1 renal cells, derived from primary cultures of pig proximal tubular cells, were incubated for 18 h at 37 degrees C in serum-free medium that contained AmpB and deoxycholate or L-AmpB at 20 micrograms of AmpB per ml, HDLs or LDLs at 0.5 mg of protein per ml, mixtures of AmpB with HDLs or LDLs, and mixtures of L-AmpB with HDLs or LDLs. HDL-associated AmpB was less toxic than AmB to LLC PK1 cells (53.0% +/- 2.5% versus 81.3% +/- 3.6% cytotoxicity; P = 0.01), while LDL-associated AmpB was as toxic as AmpB. L-AmpB, HDL-associated L-AmpB, and LDL-associated L-AmpB were less toxic to LLC PK1 cells than was AmpB (48.3% +/- 1.5%, 25.5% +/- 2.2%, and 52.2% +/- 2.5% versus 81.3% +/- 3.6% cytotoxicity; P = 0.02). To further understand why HDL-associated AmpB reduced renal cytotoxic effects, the LLC PK1 cells were examined for the presence of HDL and LDL receptors. LLC PK1 cells expressed high-affinity (K(d) = 0.0538 nanograms/ml; 96,000 sites per cell) and low-affinity (K(d) = 222.22 nanograms/ml; 77 sites per cell) LDL receptors but only a low-affinity HDL receptor (K(d) = 71.43 nanograms/ml; 2 sites per cell). HDL-associated AmpB and LDL-associated AmpB were less toxic than AmpB to trypsinized LLC PK1 cells (46.6% +/- 10.9% and 16.8% +/- 15.98% versus 74.7% +/- 7.7% cytotoxicity; P = 0.02). HDL-associated AmB and LDL associated L-AmpB were also less toxic than AmpB to the cells (20.4% +/- 6.2% and 13.5% +/- 8.6% versus 74.7% cytotoxicity; P = 0.01). The antifungal activities of AmpB and L-AmpB were not altered in the presence of HDLs or LDLs. We conclude that the reduced nephrotoxicity associated with the use of L-AmpB is related to a decreased uptake of AmpB by renal cells when AmpB is associated with HDLs because of the low level of expression of HDL receptors in these cells. PMID- 8192448 TI - Genetic alterations in streptomycin-resistant Mycobacterium tuberculosis: mapping of mutations conferring resistance. AB - We report on the identification of mutations associated with streptomycin resistance in Mycobacterium tuberculosis. Two isolates (3656 and 3976) showed a wild-type ribosomal protein, S12, but exhibited a single point mutation at 16S rRNA position 491 (C-->T) or 512 (C-->T), respectively. Sequence analysis of a third isolate (2438) revealed a single base change at 16S rRNA position 904 (A- >G). This position is equivalent to invariant position 913 of the Escherichia coli 16S rRNA gene, an A-->G transition of which has been shown previously to impair streptomycin binding and streptomycin-induced misreading in vivo. Surprisingly, strain 2438 harbors an additional mutation in the ribosomal protein S12 (Lys-88-->Gln). PMID- 8192449 TI - Comparative in vivo activities of rifabutin and rifapentine against Mycobacterium avium complex. AB - The dose-response activity of rifabutin and the comparative activities of rifabutin and rifapentine were evaluated in the beige mouse model of disseminated Mycobacterium avium complex (MAC) infection. In the dose-response study, mice were infected intravenously with approximately 10(7) viable M. avium ATCC 49601. Treatment with rifabutin at 10, 20, or 40 mg/kg of body weight was started 7 days postinfection and was administered daily for 10 days. The mice were sacrificed 3 to 5 days after the last dose. Spleens, livers, and lungs were homogenized, and viable cell counts were determined by serial dilution and plating onto Middlebrook 7H10 agar. A dose-related reduction in MAC cell counts in the organs was noted for this MAC isolate. The comparative activities of rifabutin and rifapentine were determined against a total of five MAC isolates in the beige mouse model. Rifabutin or rifapentine (20 mg/kg each) was administered to infected mice for 10 days. Groups of treated mice were compared with untreated control animals. Despite favorable in vitro susceptibility results, rifabutin and rifapentine had activities in the spleens against only two of the five MAC isolates. For these two MAC isolates, rifabutin was more active than rifapentine. These agents had activities in the lungs against three of five isolates. Further study of rifabutin or rifapentine against a broader range of clinical isolates in a murine infection model may be useful as part of the continuing development of newer rifamycins as anti-MAC agents. PMID- 8192450 TI - Streptomycin resistance in mycobacteria. AB - Streptomycin, the first antibiotic used in tuberculosis control programs, perturbs protein synthesis at the ribosome level. It is shown here that streptomycin resistance in some clinical isolates of Mycobacterium tuberculosis is associated either with missense mutations in the rpsL gene, which encodes ribosomal protein S12, or with base substitutions at position 904 in the 16S rRNA. The primary structure of the S12 protein is well conserved among the mycobacteria, even those, such as M. avium, M. gordonae, and M. szulgai, that are naturally resistant to streptomycin. This suggests that permeability barriers may be responsible for the resistance to the antibiotic. PMID- 8192451 TI - Cytofluorometric analysis of chondrotoxicity of fluoroquinolone antimicrobial agents. AB - To better understand quinolone-related arthropathy, we conceived an experimental ex vivo model using cell cultures of articular chondrocytes issued from pretreated New Zealand White rabbits (NZW). Juvenile (4- to 5-week-old) NZW were orally dosed with ofloxacin or pefloxacin (300 mg/kg of body weight for 1 day) or with pefloxacin (300 mg/kg for 7 days). Adult (5-month-old) NZW were treated with pefloxacin (300 mg/kg for 1 day). Chondrocytes were enzymatically recovered from cartilage and were analyzed by cytofluorometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and dihydrorhodamine 123 (DHR), reflecting cellular respiratory-burst activity, and rhodamine 123 (Rh123) and 10-N-nonyl-acridine orange (NAO), specific for the mitochondrial activity and mass, respectively. A significant increase in the respiratory burst was detected by DCFH-DA and DHR in all treated groups of young animals, compared with untreated control groups. No significant increase of respiratory burst was noted in older treated rabbits. The 7-day treatment resulted in a decrease in mitochondrial uptake of Rh123 and an increase in NAO uptake. Fluoroquinolone arthrotoxicity seems to involve in its early phase the respiratory burst of immature articular chondrocytes. PMID- 8192452 TI - Effect of sucralfate on absorption of norfloxacin and ofloxacin. AB - The effect of sucralfate on the pharmacokinetics of norfloxacin and ofloxacin was assessed in two separate crossover studies with healthy volunteers. In both studies, eight subjects were randomized to one of the following three regimens: a 400-mg dose of norfloxacin or ofloxacin alone, norfloxacin or ofloxacin given simultaneously with sucralfate (1 g), or norfloxacin or ofloxacin given 2 h before sucralfate. Coadministration of sucralfate reduced the bioavailability of norfloxacin and ofloxacin by 91% (P < 0.001) and 61% (P < 0.001), respectively. However, when norfloxacin and ofloxacin were given 2 h before sucralfate, there were no significant alterations in the pharmacokinetics of either fluoroquinolone. Similar results were obtained when the cumulative amount of each fluoroquinolone recovered in the urine was used to calculate bioavailability. To avoid these interactions and potential therapeutic failures, norfloxacin and ofloxacin should not be used concurrently with sucralfate. The interaction can be minimized by maximizing the time between the fluoroquinolone dose and the previous sucralfate dose and giving the fluoroquinolone at least 2 h before another sucralfate dose. PMID- 8192453 TI - Activity of fleroxacin alone and in combination with clindamycin or metronidazole in experimental intra-abdominal abscesses. AB - To assess the potential efficacy of fleroxacin in combination with clindamycin or metronidazole in mixed aerobic and anaerobic infections, we used a rat model of intra-abdominal abscesses in which the inoculum consisted of pooled rat feces mixed with BaSO4. Two hours after bacterial challenge, antimicrobial therapy was begun intravenously with regimens designed to stimulate human pharmacokinetics. A combination of clindamycin and gentamicin was included as an established treatment regimen. After 8.5 days of therapy, final bacterial counts in abscesses showed that fleroxacin alone or combined with metronidazole or clindamycin effectively eradicated Escherichia coli, with bacterial densities of < or = 2.84 +/- 0.1, < or = 2.9 +/- 0.1, and < or = 2.9 +/- 0.1 (mean +/- standard error of the mean) log10 CFU/g, respectively. The addition of either clindamycin or metronidazole to fleroxacin substantially enhanced the effectiveness of the regimens against Bacteroides fragilis, with bacterial counts of < or = 3.0 +/- 0.1 or < or = 2.9 +/- 0.1 log10 CFU/g, respectively, versus 9.2 +/- 0.2 log10 CFU/g for fleroxacin alone. The combination of metronidazole and fleroxacin also resulted in a significantly greater reduction of peptostreptococci and Bacteroides thetaiotaomicron than fleroxacin alone (< or = 2.9 +/- 0.1 versus 6.1 +/- 0.9 log10 CFU/g and 3.3 +/- 0.4 versus 8.3 +/- 0.1 log10 CFU/g, respectively). Except for those of B. fragilis, counts of other anaerobes were reduced to a greater extent by metronidazole plus fleroxacin than by clindamycin plus fleroxacin, although differences were not always significant. Metronidazole plus fleroxacin was at least as active a clindamycin plus gentamicin against all species and was significantly more active against Clostridium spp. No regimen effectively eradicated enterococci from the abscesses. These results suggest that the addition of either metronidazole or clindamycin would effectively enhance the spectrum of fleroxacin for treatment of mixed aerobic and anaerobic infections. PMID- 8192454 TI - In vitro and in vivo inhibition of ortho- and paramyxovirus infections by a new class of sulfonic acid polymers interacting with virus-cell binding and/or fusion. AB - A series of sulfonic acid polymers were shown to be potent and selective inhibitors of respiratory syncytial virus (RSV) and influenza A virus. The compounds inhibit the replication of RSV and influenza A virus in HeLa and MDCK cells, at concentrations of 0.16 and 4.0 micrograms/ml, respectively, and are nontoxic to growing cells at concentrations of > 100 micrograms/ml. The mode of antiviral action of the sulfonic acid polymers can be ascribed to inhibition of virus-cell fusion (for influenza A virus) or inhibition of both virus-cell binding and fusion (for RSV). The sulfonic acid prototype PAMPS [poly(2 acrylamido-2-methyl-1-propanesulfonic acid)], when administered intranasally to mice as a single dose of 10 or 50 mg per kg of body weight at the time of infection, completely inhibited influenza A virus replication (in lungs) and virus-associated lung consolidation in immunocompetent mice and completely protected NMRI and SCID (severe combined immune deficiency) mice against influenza A virus-associated mortality. When administered 1 h before or after virus inoculation, no protective effect was observed at a dose of 10 or 100 mg/kg. Sulfonic acid polymers exert selective inhibitory effects on RSV and influenza A virus replication. PMID- 8192455 TI - Treatment of murine candidiasis and cryptococcosis with amphotericin B incorporated into egg lecithin-bile salt mixed micelles. AB - Amphotericin B (AmB) with deoxycholate (Fungizone) and AmB incorporated into mixed micelles (AmB-mixMs) composed of egg lecithin with glycocholate, deoxycholate, or taurocholate were compared as treatments for murine infections. For mice infected with Candida albicans, treatment consisted of a single intravenous injection; for mice infected with Cryptococcus neoformans, treatment consisted of two intravenous injections. The maximal tolerated doses of AmB as Fungizone were 1.25 mg/kg of body weight in mice with candidiasis and 2.5 mg/kg of body weight in mice with cryptococcosis. The AmB-mixMs were nontoxic to mice at doses of 80 and 100 mg/kg of body weight and were therapeutically more active than the maximal tolerated dose of Fungizone in both models of infection. However, when Fungizone or AmB-mixMs were administered at equivalent doses of AmB, AmB-mixMs were more active in treating murine candidiasis, whereas Fungizone was more active in treating murine cryptococcosis. PMID- 8192456 TI - Amphotericin B incorporated into egg lecithin-bile salt mixed micelles: molecular and cellular aspects relevant to therapeutic efficacy in experimental mycoses. AB - The cellular activities of amphotericin B (AmB) used as Fungizone were compared with those of AmB complexed to either egg lecithin and glycocholate (Egam) or egg lecithin and deoxycholate (Edam). Under conditions in which leakage of K+ from erythrocytes and cultured L cells treated with Fungizone was almost complete, Egam and Edam containing concentrations of AmB severalfold greater than the concentration of AmB in Fungizone had no effect but retained the ability to decrease the level of retention of K+ in fungal cells. Analysis by absorption and circular dichroism spectroscopy demonstrated that when these formulations containing AmB at concentrations of less than 10(-5) M were added to buffer, the AmB dissociated slowly as monomers from Egam or Edam and dissociated rapidly as a mixture of monomers and self-associated species from Fungizone. We propose that in Egam and Edam, the absence of free AmB in the self-associated form reduces the toxicity of AmB to mammalian cells, whereas the presence of monomeric AmB results in the retention of the antifungal activities of these complexes. PMID- 8192457 TI - Dideoxynucleoside resistance emerges with prolonged zidovudine monotherapy. The RV43 Study Group. AB - Human immunodeficiency virus type 1 (HIV-1) isolates resistant to zidovudine (ZDV) have previously been demonstrated to exhibit in vitro cross-resistance to other similar dideoxynucleoside agents which contain a 3'-azido group. However, cross-resistance to didanosine (ddI) or dideoxycytidine (ddC) has been less well documented. ZDV, ddI, and ddC susceptibility data have been collected from clinical HIV-1 isolates obtained by five clinical centers and their respective retrovirology laboratories. All subjects were treated only with ZDV. Clinical HIV 1 isolates were isolated, amplified, and assayed for drug susceptibility in standardized cultures of phytohemagglutinin-stimulated donor peripheral blood mononuclear cells obtained from healthy seronegative donors. All five cohorts showed a correlation between decreased in vitro susceptibility to ZDV and decreased susceptibility to ddI and ddC. For each 10-fold decrease in ZDV susceptibility, an average corresponding decrease of 2.2-fold in ddI susceptibility was observed (129 isolates studied; P < 0.001, Fisher's test of combined significance). Similarly, susceptibility to ddC decreased 2.0-fold for each 10-fold decrease in ZDV susceptibility (82 isolates studied; P < 0.001, Fisher's test of combined significance). These data indicate that a correlation exists between HIV-1 susceptibilities to ZDV and ddI or ddC for clinical HIV-1 isolates. PMID- 8192458 TI - Comparison of cefuroxime axetil and amoxicillin-clavulanate suspensions in treatment of acute otitis media with effusion in children. AB - Two hundred sixty-three pediatric patients from the ages of 3 months to 11 years were enrolled in a randomized, investigator-blinded, multicenter study comparing the clinical and bacteriological efficacies and safety of cefuroxime axetil suspension (CAE) with those of amoxicillin-clavulanate suspension (AMX-CL) in the treatment of acute otitis media with effusion. Patients received CAE at 30 mg/kg of body weight per day (n = 165) in two divided doses or AMX-CL at 40 mg/kg/day (n = 98) in three divided doses for 10 days. The primary pathogens among 200 isolates from pretreatment cultures of middle ear fluid were identified as follows: Haemophilus influenzae (39%), over a third of which were beta-lactamase positive; Streptococcus pneumoniae (34%); and Moraxella catarrhalis (16%). Pathogens were eradicated or presumed to be eradicated from 81% (95 of 118) and 76% (50 of 66) of bacteriologically evaluable patients in the CAE and AMX-CL groups, respectively. A satisfactory clinical response (cure or improvement with or without resolution of effusion) occurred in 113 (77%) of 146 clinically evaluable patients in the CAE group and in 66 (74%) of 89 evaluable patients in the AMX-CL group. Clinical failure or recurrence (within 2 weeks following the completion of treatment) occurred in 22 and 26% of CAE- and AMX-CL-treated patients, respectively. Drug-related adverse events occurred in 18% of CAE treated patients, whereas they occurred in 39% of AMX-CL-treated patients (P < 0.001); diarrhea or loose stools was the most commonly reported adverse event (CAE, 12%; AMX-CL, 31%; P < 0.001). These results indicate that CAE given twice daily is as effective as AMX-CL given three times daily in the treatment of acute otitis media with effusion in pediatric patients, but CAE was associated with significantly fewer drug-related adverse events. PMID- 8192459 TI - Digoxigenin-ampicillin conjugate for detection of penicillin-binding proteins by chemiluminescence. AB - This paper describes a highly sensitive new method for the identification of penicillin-binding proteins (PBPs) that is based on the use of an ampicillin digoxigenin conjugate (DIG-AMP conjugate) which is detected by immunoblotting and chemiluminescence. The sensitivity of chemiluminescence permitted X-ray film exposure times to be decreased to minutes, as opposed to the days or weeks which are requisite when conventionally radiolabeled beta-lactams are used. Coupling of ampicillin to digoxigenin yielded a product containing digoxigenin (detected by chemiluminescence) which also was inhibitory for Staphylococcus aureus and Escherichia coli. Unconjugated digoxigenin at concentrations of up to 100 micrograms/ml was not inhibitory for either organism. For S. aureus the MICs of DIG-AMP (0.7 microgram of conjugated ampicillin per ml) and of free ampicillin (0.5 microgram/ml) were comparable, indicating that ampicillin retained its bioactivity when coupled to digoxigenin. However, for E. coli the MICs of DIG-AMP (70 micrograms of conjugated ampicillin per ml) and of free ampicillin (8 micrograms/ml) were widely disparate, suggesting that the DIG-AMP conjugate was too large and/or hydrophobic to traverse the E. coli outer membrane via porins. DIG-AMP binding assays with E. coli and S. aureus cell envelopes revealed profiles of PBPs similar to those detected with 125I-ampicillin or [3H]penicillin. DIG-AMP binding to PBPs was completely inhibited in competition experiments with free ampicillin or penicillin, supporting the specificity of the DIG-AMP conjugate for PBPs. DIG-AMP thus represents an advantageous alternative to radioactive beta-lactams for the identification and analysis of PBPs. PMID- 8192460 TI - In vivo activity of ajoene against rodent malaria. AB - Ajoene (4,5,9-trithiadodeca-1,6,11-triene 9-oxide), a product initially isolated from extracts of garlic (Allium sativum), was tested for its antimalarial activity in vivo in a well-characterized murine model. A single ajoene dose of 50 mg/kg, on the day of infection, suppressed the development of parasitemia; there were no obvious acute toxic effects from the tested dose. The combination of ajoene (50 mg/kg) and chloroquine (4.5 mg/kg), given as a single dose on the day of the infection, completely prevented the subsequent development of parasitemia in treated mice. PMID- 8192461 TI - Rapid emergence of quinolone resistance in cirrhotic patients treated with norfloxacin to prevent spontaneous bacterial peritonitis. AB - We carried out quantitative culturing of stools from 31 hospitalized alcoholic patients with cirrhosis and ascites, before treatment with 400 mg of norfloxacin per day, weekly for the first month, and then every 2 weeks thereafter for 15 to 229 days (median, 54 days). Members of the family Enterobacteriaceae virtually disappeared from the stools (< 10(2)/g), but treatment had little effect on enterococci. No selection of resistant organisms occurred in 15 patients, but the remaining 16 patients developed fecal organisms resistant to fluoroquinolones between days 14 and 43 of treatment (median, 25 days). Staphylococcus aureus was isolated four times, coagulase-negative Staphylococcus spp. were isolated six times, Citrobacter freundii was isolated four times, Enterobacter cloacae was isolated three times, Klebsiella oxytoca was isolated twice, Proteus rettgeri was isolated once, and untypeable streptococci were isolated six times. Some isolates persisted, while others were transient (one to seven consecutively positive cultures). The MICs of four quinolones (nalidixic acid, norfloxacin, ofloxacin, and ciprofloxacin) were determined by use of experimental microwell strips (ATB CMI; Biomerieux S.A.). All the strains isolated before treatment were susceptible to the four quinolones, with low MICs, whereas those isolated during norfloxacin treatment were highly resistant. Long-term norfloxacin administration thus carries a risk of disturbing the bacterial ecology in these patients, suggesting that digestive decontamination should no longer be prescribed routinely to cirrhotic patients with ascites. PMID- 8192462 TI - Comparison of tests for detection of methicillin-resistant Staphylococcus aureus in a clinical microbiology laboratory. AB - By microdilution testing, 186 of 1,450 clinical isolates of Staphylococcus aureus were preliminarily classified as oxacillin resistant (MIC > or = 4 micrograms/ml); 15 of these isolates gave conflicting results by alternative methods and were studied further. Only 2 of these (MIC > 4 micrograms/ml) were mecA positive; 13 were inhibited by oxacillin at 4 micrograms/ml. Significant numbers of S. aureus strains classified as resistant with an oxacillin MIC of 4 micrograms/ml may prove susceptible by other methods. PMID- 8192463 TI - beta-Lactam resistance of motile Aeromonas isolates from clinical and environmental sources. AB - The MICs of various beta-lactams for 182 isolates of Aeromonas species, i.e., A. hydrophila (n = 101), A. sobria (n = 69), and A. caviae (n = 12), from clinical and environmental sources were determined by an agar dilution technique. All strains were resistant to ampicillin and susceptible to aztreonam. A. sobria and A. caviae demonstrated lower resistance rates than A. hydrophila. Penicillin hydrolyzing beta-lactamases were detected in all strains. PMID- 8192464 TI - Aerosolized amphotericin B-liposomes for treatment of systemic Candida infections in mice. AB - Mice lethally infected with Candida albicans were exposed to small-particle aerosols containing amphotericin B-liposomes. The drug, when administered twice daily for 2 h (0.58 mg/kg of body weight per day) on days 1, 2, and 3 postinoculation, significantly reduced the numbers of Candida organisms in the kidneys. Aerosol treatment increased the survival time of mice given 2 2-h treatments once a week for 4 weeks. A twice-weekly, 2-h small-particle aerosol administration of amphotericin B-liposomes for 1, 2, or 3 weeks significantly increased both the mean time of survival and percent survival. PMID- 8192465 TI - In vitro studies on stability and development of metronidazole resistance in Helicobacter pylori. AB - Seventy isolates of Helicobacter pylori from antral biopsy samples were tested for their susceptibilities to metronidazole by agar dilution. Seven (10%) of these clinical isolates appeared to be resistant to metronidazole. Sixty-three strains were susceptible. In 42 (67%) of the 63 susceptible isolates, resistant isolates were obtained by serial passage on plates containing subinhibitory concentrations of metronidazole. In 10 of these 42 strains, the acquired resistance appeared to be unstable. The difference between the stability of resistance that occurred after one or two passages and the stability of resistance that occurred after three passages was statistically significant (P < 0.006). Primary resistance in clinical isolates was a stable phenomenon. Whether the resistance that emerges during therapy in patients is stable or unstable needs to be established. PMID- 8192466 TI - Physicochemical cell damage in relation to lethal amphotericin B action. AB - A direct relationship between the concentration-dependent rate of amphotericin B induced K+ release from Candida albicans and the concentration-dependent rate of killing by the drug was established. This relationship together with the observed rapidity of both release and killing action supports the conclusion that the lethal action of amphotericin B is primarily physicochemical in nature. PMID- 8192468 TI - Susceptibilities of 123 Xanthomonas maltophilia strains to clinafloxacin, PD 131628, PD 138312, PD 140248, ciprofloxacin, and ofloxacin. AB - The susceptibilities of 123 clinically isolated strains of Xanthomonas maltophilia to six fluoroquinolones (clinafloxacin, PD 131628, PD 138312, PD 140248, ciprofloxacin, and ofloxacin) were examined by microdilution MIC methodology. Clinafloxacin and PD 131628 were the most active compounds tested (MICs for 50% of the strains tested [MIC50s] of 0.5 and 1.0 microgram/ml and MIC90s of 2.0 and 4.0 micrograms/ml, respectively). PD 138312, PD 140248, ciprofloxacin, and ofloxacin were less active, with MIC50s ranging from 4.0 to 8.0 micrograms/ml and MIC90s of 16.0 micrograms/ml for all four compounds. Only clinafloxacin and PD 131628 were active against ciprofloxacin-resistant strains, with MIC50s of 0.5 and 1.0 microgram/ml and MIC90s of 2.0 and 4.0 micrograms/ml, respectively. PMID- 8192467 TI - Oral, subcutaneous, and intramuscular bioavailabilities of the antiviral nucleotide analog 9-(2-phosphonylmethoxyethyl) adenine in cynomolgus monkeys. AB - Intravenous, subcutaneous, intramuscular, and oral pharmacokinetics of the antiretroviral nucleotide analog [9-(2-phosphonylmethoxyethyl)adenine] (PMEA) were examined in a crossover study with four cynomolgus monkeys using 14C labelled drug at 10 mg/kg of body weight (20 microCi/kg). Plasma radioactivity declined biexponentially following intravenous administration. Radiochromatography of plasma revealed an absence of PMEA metabolites. Intramuscular and subcutaneous bioavailabilities of PMEA were (means +/- standard deviation) 126% +/- 30% and 101% +/- 25%, respectively, supporting the clinical utility of these routes. The oral bioavailability of PMEA in this species (4.0% +/- 1.0%) appeared to be limited by intestinal permeability and is likely to be equally low in humans. PMID- 8192469 TI - Saperconazole therapy of murine disseminated candidiasis: efficacy and interactions with amphotericin B. AB - The efficacy of a new triazole antifungal agent, saperconazole, in a murine model of disseminated candidiasis was studied. Mice were intravenously infected with Candida albicans blastoconidia and treated for 14 days with oral saperconazole, intraperitoneal amphotericin B, or a combination of these. Amphotericin B alone was the most efficacious in prolonging survival and in decreasing renal colony counts, usually with complete sterilization of the kidneys by the end of the treatment course. Saperconazole improved survival rates and effected a decrease in renal colony counts, but kidneys were not microbiologically sterilized. Combination therapy with saperconazole and amphotericin B did not result in a decrease in the efficacy of amphotericin B by either end point (survival or renal colony counts). High-pressure liquid chromatographic analysis of saperconazole concentrations in serum indicated low levels of absorption of the drug. We conclude that saperconazole is effective in the treatment of murine invasive candidiasis and that the theoretical concern about adverse interactions between the two drugs does not apply to the dosages studied in these experiments. PMID- 8192470 TI - Antibacterial synergism of polymyxin B nonapeptide and hydrophobic antibiotics in experimental gram-negative infections in mice. AB - Polymyxin B nonapeptide, derived by cleavage of the fatty acyl diaminobutyric acid from polymyxin B, is considerably less toxic, lacks bactericidal activity, and retains its ability to render gram-negative bacteria susceptible to several antibiotics by permeabilizing their outer membranes. The peptide rendered all 53 polymyxin-susceptible strains tested more susceptible to novobiocin, lowering the MIC of novobiocin eightfold or more. The combination of polymyxin B nonapeptide with novobiocin or with erythromycin administered intraperitoneally in multiple doses synergistically protected mice infected with gram-negative bacteria. This combination may be clinically useful because of the apparent rarity of the acquisition of resistance. PMID- 8192471 TI - In vitro susceptibility of the opportunistic fungus Cryptococcus neoformans to anthelmintic benzimidazoles. AB - Ten benzimidazole derivatives and amphotericin B were tested in vitro against three isolates of Cryptococcus neoformans. Drug concentrations inhibiting 50% of growth (IC50s) were determined. Four derivatives, including mebendazole and albendazole, had moderately high activities (IC50 = 0.1 to 0.3 microgram/ml). Fenbendazole, however, was 10-fold more active (IC50 = 0.01 to 0.02 microgram/ml) and also 2-fold more active than amphotericin B. Ten additional clinical isolates of C. neoformans were tested against fenbendazole, mebendazole, and albendazole; similar susceptibilities were observed. Drug concentrations lethal to 90% of the cells (LC90s) were determined for two isolates. The LC90s of albendazole and mebendazole were 0.92 to 2.1 micrograms/ml, and those of fenbendazole were 0.06 to 0.07 microgram/ml; the latter are eight to ninefold lower than the LC90s of amphotericin B that were obtained. Spontaneously arising mutants displaying partial resistance to fenbendazole arose at a low frequency (5 x 10(-9). PMID- 8192472 TI - Identification of mutations in 23S rRNA gene of clarithromycin-resistant Mycobacterium intracellulare. AB - Clarithromycin is a potent macrolide that has been used for treating infections with nontuberculous mycobacteria. Pairs of susceptible and resistant Mycobacterium intracellulare strains were obtained from patients with chronic pulmonary M. intracellulare infections undergoing monotherapy with clarithromycin. Nucleotide sequence comparisons of the peptidyltransferase region in 23S rRNAs from parental and resistant strains revealed that in three of six resistant strains, for which the MIC was > 32 micrograms/ml, a single base was mutated (Escherichia coli equivalent, A-2058-->G, C, or U). As the modification of adenine 2058 by dimethylation is a frequent cause of macrolide resistance in a variety of different bacteria, we suggest that mutation of A-2058 confers acquired resistance to clarithromycin in M. intracellulare. PMID- 8192473 TI - Bactericidal activities of peptide antibiotics against multidrug-resistant Enterococcus faecium. AB - Multidrug-resistant Enterococcus faecium has emerged as a serious pathogen for which no effective therapy has been established. In this report, we describe the activities of two peptide antibiotics, ramoplanin and daptomycin, against 15 isolates of E. faecium resistant to vancomycin, ampicillin, and aminoglycosides using time-kill experiments. Both antibiotics were rapidly bactericidal when tested in broth; however, the addition of 50% serum resulted in significant regrowth. The combination of ampicillin with either ramoplanin or daptomycin largely prevented this regrowth. These peptide antibiotics showed good activity against these pathogens. While the development of daptomycin has been halted, ramoplanin may hold promise for the therapy of multidrug-resistant E. faecium, especially when combined with ampicillin. PMID- 8192474 TI - Identification of TEM-26 beta-lactamase responsible for a major outbreak of ceftazidime-resistant Klebsiella pneumoniae. AB - An epidemic of nosocomial ceftazidime-resistant Klebsiella pneumoniae was correlated with production of a ceftazidime-hydrolyzing enzyme with an isoelectric point of 5.6 (BMH-1). BMH-1 was encoded on a large transferable plasmid conferring multiple antibiotic resistance. The gene that encodes BMH-1 was identical to the gene that encodes the TEM-26 extended-spectrum beta lactamase. PMID- 8192475 TI - Penetration of vancomycin into mediastinal and cardiac tissues in humans. AB - Vancomycin penetration into heart tissues (valves, myocardium, auricles, and pericardium) and mediastinal tissues (fat and sternal bone) was evaluated after two regimens of vancomycin administration. Ten patients were given 15 mg of vancomycin per kg of body weight before anesthesia. Ten other patients received the same dose and then a second 7.5-mg/kg dose at the time of initiation of cardiopulmonary bypass. Similar and satisfactory vancomycin tissue penetrations were observed in both groups. However, for some patients in the two groups, vancomycin levels in tissue were less than the MICs for potential pathogens (Staphylococcus aureus and Staphylococcus epidermidis). PMID- 8192476 TI - Reduction of matrix metalloproteinase 8-neutrophil collagenase levels during long term doxycycline treatment of reactive arthritis. AB - The aim of this work was to determine whether human polymorphonuclear neutrophilic interstitial collagenase (matrix metalloproteinase 8 [MMP-8]) levels are reduced during long-term doxycycline treatment in humans with reactive arthritis. Serum MMP-8 levels were reduced (mean +/- standard error of the mean, 678.9 +/- 185.6 versus 491.2 +/- 144.8 ng of MMP-8 per ml), but not statistically significantly. However, the reduction of salivary MMP-8 levels was statistically significant (3,729 +/- 1,905.3 versus 1,866 +/- 780.0 ng of MMP-8 per ml, P < 0.05). This study demonstrated that a 2-month regimen of doxycycline can reduce MMP-8 levels in serum and especially in body fluids (i.e., saliva) containing inflammatory exudates and thus may contribute to reduced tissue destruction. PMID- 8192477 TI - (6S)-6-fluoroshikimic acid, an antibacterial agent acting on the aromatic biosynthetic pathway. AB - (6S)-6-Fluoroshikimic acid inhibited the growth of Escherichia coli B on minimal medium (MIC, 0.25 micrograms ml-1), and it protected mice challenged intraperitoneally with the same organism (50% protective dose, 0.06 mg kg of body weight-1). We propose that inhibitors of bacterial aromatic biosynthesis have the potential for use in human medicine. PMID- 8192479 TI - Lessons from history can serve us today. PMID- 8192478 TI - Perioperative nurses face critical challenges. PMID- 8192480 TI - Staffing requirements. PMID- 8192481 TI - Staffing requirements. PMID- 8192482 TI - The transfer of protein allergens from latex gloves. A study of influencing factors. PMID- 8192483 TI - Latex sensitivity. Controlling health care workers', patients' risks. PMID- 8192484 TI - Diverticular disease. Surgical options, patient management. AB - Diverticular disease is a common and occasionally complicated disease in our western society. Although the exact etiology is unknown, diet is thought to be a contributing factor to the formation of diverticula. Diverticular disease most often is managed medically. When surgery is indicated, perioperative nursing care is based on knowledge of the disease process and attention to the physical and emotional needs of the patient. PMID- 8192485 TI - The do-not-resuscitate order. Moral responsibilities of the perioperative nurse. AB - To provide care that is consistent with a patient's view of his or her best interests, the perioperative nurse must be a knowledgeable, informed member of the OR team. This knowledge must include familiarity with and understanding of all policies that relate to the care of the surgical patient--including DNR policies. The nurse must be willing to assert his or her moral agency in developing DNR policies that will eliminate potential conflict among the OR team members regarding patients with DNR designations. Only by being a knowledgeable moral agent can the perioperative nurse function as an effective advocate of the patient as a person. PMID- 8192486 TI - Sales representatives in the OR. Are they prepared? PMID- 8192488 TI - Scrubs, scrubs, who's got the scrubs? PMID- 8192487 TI - Operating room scheduling. Factors to consider. PMID- 8192489 TI - Proposed recommended practices. Use of the pneumatic tourniquet. Association of Operating Room Nurses. PMID- 8192490 TI - Legislation regarding advanced practice nursing abundant in past year. PMID- 8192491 TI - Future HIV prevention method for women. PMID- 8192492 TI - The effects of diabetes on penile somato-afferent system. AB - The direct evaluation of the autonomic nervous system to detect the neurogenic component of erectile dysfunction in men is not possible. Biothesiometry, a vibration perception test, is a simple method for the assessment of the penile somato-afferent system. A nomogram for the evaluation of somato-afferent system has been developed utilizing the biothesiometer in healthy men. This nomogram was used to compare the biothesiometric values of potent and impotent diabetic patients. According to our data, the radix penis is selectively damaged by diabetes mellitus in the first stage of the disease, whereas the glans penis is damaged later on when the disease reaches the stage of impotence. PMID- 8192493 TI - [Value of preoperative autotransfusion in elective urologic surgery]. AB - Over a period of 5 months, 50 patients were entered into the preoperative autologous blood donation program of our Service. Two patients were excluded; one had previously had an acute myocardial infarction and the other had epilepsy. The remaining 48 patients, which accounted for one third of our elective surgery procedures, all accepted to enter the program. These patients were not more severely anemic than the other patients not in the program and who underwent the same surgical procedures. No patients required homologous blood transfusion and no complications ascribable to the procedure were observed. Although it is not utilized widely to date, predeposited autologous blood transfusion is a safe and efficient method, with no remarkable morbidity, even in patients aged over 65 years, the age group of one half of our patients. Autologous blood transfusion programs are necessary. The indications, the exclusion criteria for patients at high risk and the objective parameters for evaluating its success must be established. PMID- 8192494 TI - [Endoscopic biopsy in the staging of infiltrating tumor of the bladder]. AB - From July, 1990 to June, 1991, a prospective study was conducted on 65 patients with infiltrating bladder tumor to determine the possibility of distinguishing T2 from T3 tumors endoscopically. Sixty-six tumors were resected, including all of the bladder wall, and samples of perivesical fat were obtained from the tumor bed. The pathologist found infiltration of the bladder muscle wall in 50 cases (75.6%) and classified 12 tumors as T2 and 38 as T3. Fifty-five per cent of the T3a tumors were reclassified as T3b on the basis of the indirect signs of the pelvic scan and bimanual palpation performed under anesthesia. The clinical staging correlated with the pathological findings in 52.6% of the 19 cases of pT3b that underwent radical cystoprostatectomy; 31.7% of the pT3b tumors were clinically understaged, mainly due to prostatic infiltration. We can conclude from our findings that the differential diagnosis between pT2 and pT3 tumors is possible by endoscopic resection for most of the infiltrating bladder tumors; however, pT3a tumors cannot be distinguished from pT3b tumors with sufficient reliability. PMID- 8192495 TI - [Postoperative fusiform cell nodule. Relationship with other benign fibrous proliferations]. AB - We report on a patient who developed postoperative spindle cell nodule one month following TURP for prostatic adenocarcinoma. The foregoing was compared with other benign fibrous lesions from our records: one case of nodular fasciitis and one case of proliferative myositis. Although they were all well-defined and clinically distinct disease entities, a very close relationship concerning their origin was demonstrated histologically and immunohistochemically. PMID- 8192496 TI - [Usefulness of carcinoembryonic antigen in transitional cell carcinoma of the bladder]. AB - Carcinoembryonic antigen (CEA), described by Gold and Freedman, was the first fetal tumor antigen isolated in tumor homogenates. The present study investigated the biological behaviour of CEA in superficial transitional cell carcinoma of the bladder, deep localized and disseminated. The study comprised 100 subjects; 30 carefully-selected healthy subjects comprised the first group and 70 patients with a diagnosed transitional cell carcinoma of the bladder comprised the second group. Serum CEA was determined by enzyme immunoassay (CEA, EIA, Roche). Our results suggest that serum CEA determination affords no diagnostic benefit in this type of malignant tumor. PMID- 8192497 TI - [Posterior urethral valves. Prognostic factors in the clinical course]. AB - A retrospective study was conducted in 27 patients with posterior urethral valves that had been treated between 1978 and 1991 in order to determine the prognostic factors of renal function. Patient age ranged from 12 days to 12 years. The mean follow-up was 5 years. Urinary infection was the most common symptom. We used micturating cystography, intravenous urography, US, urodynamics and cystoscopy for the diagnosis. Renal function was evaluated by serum creatinine. All the valves were treated endoscopically by transurethral fulguration. Nineteen patients also underwent ureteral reimplantations. There were 5 nephrectomies and 12 upper tract diversions. There was a strong correlation between serum creatinine at the beginning and after a year and the final renal function (p > 0.001 and p = 0.030, respectively). The correlation between the age and initial serum creatinine was almost significant (p = 0.065). There was no significant correlation between the age at diagnosis, the reflux and the final renal function. PMID- 8192498 TI - [Experimental kidney transplantation in rats. Technical, functional, and histologic aspects]. AB - In recent years, different experimental transplantation techniques have been developed in animals to gain further insight into the immunologic and non immunologic processes occurring in grafts. Microsurgery permits the application of these procedures to small animals, as the rat. We present our experience in experimental transplantation in rats, with special reference to isogenic transplantation (inbred animals), leaving solely the graft in the receptor. The technical characteristics, the analytic and histologic findings after transplantation are described. PMID- 8192499 TI - [Renal trauma in children: our experience and review of the literature]. AB - Twenty-seven cases of kidney injury in children under 15 years old are reviewed. All of them were diagnosed, treated and subsequently followed in our Service between 1979 and 1992. Clinical evaluation, blood and urine analyses, and imaging techniques are the three basic tools in the management of kidney injuries. Regarding imaging techniques, dynamic CT is currently the best diagnostic method, mainly due to its high anatomic resolution and because it permits evaluation of renal function and of possible associated lesions in other organs. Kidney injuries were classified into three categories: I (18 cases), II (4 cases), and III (4 cases). The last injury affected a pathological kidney. Emergency surgical procedures were performed in 7 cases (25.9%): 2 were category II, 4 category III, and the pathologic kidney that suffered trauma. Surgery was deferred in one case (category II) and the remaining 19 cases (74.1%) were treated conservatively: 18 were category I and 1 category II. Nephrectomy was required only for the pathologic kidney. All the other kidneys were preserved. PMID- 8192500 TI - [Macro-orchidism: new pathogenetic and histopathologic aspects]. AB - Macro-orchidism (MO) is the increase of the testicular volume, up to 25 ml in the adult male. It is frequently associated with mental retardation (MR) with fragile X-chromosome (FXC) (Martin-Bell syndrome). Sometimes it is of unknown origin and is called "benign idiopathic macro-orchidism" (BIMO). MO has also been described in association with bilateral testicular tumors, idiopathic precocious puberty, juvenile hypothyroidism and, more rarely, with congenital testicular cysts (cystic testicular dysplasia) and testicular microlithiasis in a patient treated with GH. The most common presentation is MR associated with MO, with positive or negative FXC. Among MO with MR and FXC-marfanoid habitus patients have been described and in the Atkin-Flaitz syndrome patients. Management of MO must be conservative in all cases and testicular biopsy must only be performed to diagnose leukemic infiltration or carcinoma in situ (CIS), or as the last fertility diagnostic test in BIMO. A wide range of primary testicular lesions may histopathologically be found: preserved spermatogenesis tubes, only Sertoli cell pattern and complete tubular sclerosis. Interstitial edema, frequently implicated in the MO pathogeny, does not explain by itself the important increase in testicular volume. In our laboratory, we have demonstrated that the increment of the testicular volume in MO is associated with a significant increase in the length of the seminiferous tubules. MO may pathogenically be intimately related to some hormonal regulation mechanism or to a higher seminiferous tubule sensitivity to FSH. PMID- 8192501 TI - [Complex renal lithiasis: conservative surgery]. AB - We report a case of complicated renal lithiasis which had been successfully treated by conservative surgery. The present case shows that this surgical procedure continues to be a valid therapeutic option for this pathology, although occasionally the new, less invasive treatment modalities that continue to develop are utilized in the treatment of renal lithiasis far beyond the indications. PMID- 8192502 TI - [Lipoma of the spermatic cord. Report of a case]. AB - Thirty per cent of spermatic cord tumors are malignant and the remaining 70% are benign, lipoma being the most common benign lesion. Although it is the most common tumor of the spermatic cord, its clinical presentation is rare. It is an extratesticular intrascrotal mass that grows relatively rapidly, with no other clinical symptoms or signs. The clinical diagnosis is confirmed by US, CT and, occasionally, by exploratory scototomy. Treatment is by surgical excision. PMID- 8192503 TI - [Cytology positive for malignant cells in hydrocele secondary to testicular seminoma]. AB - Finding tumor cells in the fluid of hydrocele secondary to testicular tumor is rare and may be due to the fact that hydrocele fluid cytology has not been studied systematically. The presence of malignant cells in the hydrocele fluid may be ascribed to two mechanisms: retrograde lymphatic flow from the infiltrated retroperitoneal lymph nodes or from tumor directly invading the tunica albuginea and vaginalis testis, with cells passing into the cavity of the vaginalis. Only two cases of hydrocele secondary to testicular seminoma with vaginalis fluid cytology positive for malignant seminomatous cells have been previously reported in the literature. To our knowledge, the case reported herein is the third. These three cases are briefly discussed. PMID- 8192504 TI - [Ureteral stenosis caused by benign polyp. A new case]. AB - Congenital ureteral stricture may infrequently be associated with polyps which further exacerbate this obstructive condition. The polyps may grow and cause symptoms in the elderly patients. A recent case is described and the literature reviewed. PMID- 8192505 TI - [Scrotal fistula, as clinical manifestation of ureteral ectopy connecting to seminal vesicle]. AB - We report on a 33-year-old male with left ureteral ectopia into the seminal vesicle and ipsilateral renal agenesia, whose outstanding clinical manifestation was scrotal fistula directly from the seminal vesicle. This condition was diagnosed correctly by fistulography. The usefulness of the foregoing method is underscored. PMID- 8192507 TI - [Synchronous metastasis of renal adenocarcinoma to gallbladder and ipsilateral adrenal gland]. AB - Herein we describe a patient in whom a renal mass had been detected. He had no previous urological symptoms or signs, but had undergone laryngectomy in 1989 for well-differentiated squamous cell carcinoma of the glottic region. The radiological and ultrasound evaluations disclosed a right renal mass, a mass in the ipsilateral adrenal gland and a polypoid mass in the gallbladder. The patient underwent radical nephrectomy, adrenalectomy and cholecystectomy. The surgical specimens of the gallbladder and adrenal gland showed histological evidence of clear cell carcinoma with the same characteristics as those of the primary renal tumor. PMID- 8192506 TI - [Acquired cystic renal disease: a case of intracystic hemorrhage simulating renal tumor]. AB - We report a case of intracystic hemorrhage in a patient with acquired cystic kidney disease, undergoing hemodialysis. A surgical procedure was performed owing to the discrepancy between the clinical and radiological findings. The histological analyses revealed no evidence of kidney tumours. PMID- 8192509 TI - Simulation experiments for catching Oncomelania in irrigation canals. PMID- 8192508 TI - [Retroperitoneal angiomyolipoma stemming from the psoas. Comments on a case]. AB - We report a case of subclinical retroperitoneal tumor in a young patient. Although different diagnostic techniques were utilized (US, urography, CT, etc.), the tumor type could not be determined preoperatively. A malignant tumor was suspected, therefore surgical excision was warranted. The pathological analysis disclosed an angiomyolipoma in the psoas muscle, a benign tumor in an uncommon site. The foregoing finding prompted us to report the present case. PMID- 8192510 TI - Hepatic metabolism in severe falciparum malaria: caffeine clearance study. AB - Falciparum malaria is known to cause abnormalities in the liver. Hepatic metabolism in patients with falciparum was studied by caffeine clearance and the results were related to the severity of the disease. Caffeine (3.5 mg/kg) was administered orally to patients with severe (N = 10) or uncomplicated (N = 9) falciparum malaria. The plasma clearances during illness averaged 0.67 +/- 0.27 ml/min kg for the severe cases and 0.98 +/- 0.36 ml/min kg for the uncomplicated cases (P < 0.05). In the severe patients, clearances during illness (0.67 +/- 0.27 ml/min kg) were less than those in convalescence (2.15 +/- 0.91 ml/min kg) (P < 0.0001). However, in the uncomplicated cases, the clearances during illness and in convalescence were similar (P > 0.05) and clearance rates in convalescence were similar for the severe and uncomplicated cases (P > 0.05). Hepatic microsomal metabolism is apparently slow in severe falciparum malaria but reverts to normal in convalescence. Liver metabolic function does not appear to be significantly affected in uncomplicated malaria. PMID- 8192511 TI - Proliferative responses of lymphocytes from malaria patients and healthy controls to isolated, Plasmodium falciparum schizont antigens. AB - The specificity of lymphocyte proliferative responses of malaria patients and healthy control subjects was analysed using antigen fractions from soluble extracts of purified Plasmodium falciparum schizonts. Fractions of 14-250 kDa were separated by SDS-PAGE, blotted to nitrocellulose membranes and eluted for use in lymphocyte stimulation studies. Lymphocyte proliferation following stimulation with the separated protein fractions demonstrated that the fractions were recognized only by patients' T cells. Moreover, only the fractions including proteins of 36-250 kDa were immunogenic to the T cells. The pattern of response against each fraction differed between patients, indicating an HLA-dependent genetic restriction in the T cell activation. PMID- 8192512 TI - Cutaneous leishmaniasis in Tachira State, Venezuela. AB - Cutaneous and mucocutaneous leishmaniases are widely spread in the mountainous Andean regions of South America. In Venezuela, these regions consist of the coffee-growing states of Trujillo, Merida and Tachira. Entomological and parasitological investigations in three geographically different climatic zones (Lomas Bajas, Delicias and La Grita) in Tachira state have shown a predominance of the sandfly species Lutzomyia spinicrassa (verrucarum group) and two Leishmania species, Leishmania mexicana and Leishmania braziliensis. Two transmission cycles appear to occur: a peridomestic cycle in Lomas Bajas and a sylvatic one in Delicias and La Grita. PMID- 8192513 TI - Antimony determination in tissues and serum of hamsters infected with Leishmania garnhami and treated with meglumine antimoniate. AB - Hamsters were experimentally infected with Leishmania garnhami and then treated for 10 days with N-methyl-glucamine antimoniate (Glucantime); 60 mg/kg/day by intramuscular (im) or intralesional (il) routes. Hydride generation-atomic absorption spectroscopy was used to determine the concentrations of SbIII and SbV in the blood serum and total Sb in the tissues of the hamsters from 1 to 30 days after initiation of the treatment. Serum concentrations of SbIII and SbV were always similar. Total Sb concentrations were significantly higher in the relatively parasite-rich spleen and lesion than in any other tissue, whether treatment had been given im or il. Reduction of SbV to SbIII is probably associated with decreasing size and healing of the leishmanial ulcers. Tissue Sb kinetics is related to Leishmania behaviour and attention is drawn to the use of antimonial pentavalent compounds for diseases, other than leishmaniasis, that can affect the heart, liver and/or spleen, such as Chagas disease. PMID- 8192514 TI - Visceral leishmaniasis in Ethiopia. III. The magnitude and annual incidence of infection, as measured by serology in an endemic area. AB - A serological study of visceral leishmaniasis was carried out in a cohort of people in an endemic area of Ethiopia. The people were tested three times, at 6 monthly intervals. Seroprevalence at the start was 112 per 1000, and the annual rate of conversion from negative to positive was estimated as 106 per 1000. Both seroprevalence and incidence of seroconversion increased with age, and males showed higher rates than females, with a male:female ratio of seroconversion of 2:1. Accumulation of 6-monthly seroconversion rates was considered to give a better estimate of the annual rate itself, as the half-life of positive serology was only around 3 months. PMID- 8192515 TI - Initial observation on albendazole in combination with cimetidine for the treatment of human cystic echinococcosis. AB - Concentrations of albendazole were measured, by high-pressure liquid chromatography, in 19 patients being treated for cystic echinococcosis. All of the patients were given three 4-week courses of albendazole (20 mg/kg/day), separated by 10-day-long drug-free intervals. Seven patients also received three courses of cimetidine (10 mg/kg/day). Concentrations of albendazole sulphoxide (ABZSX) were significantly higher in samples of bile and hydatid cyst fluid from the patients receiving albendazole and cimetidine than in those from patients receiving albendazole alone (P < 0.05). The therapeutic benefit of the combined drug treatment, which was well-tolerated, was more than that with albendazole alone. PMID- 8192516 TI - Non-bacterial diarrhoea in children in the Philippines. AB - In a 25-month prospective study of diarrhoeal disease in 236 hospitalized Filipino children under 12 years of age, a potential enteropathogen was detected in 235 cases (> 99%). Viruses, found in 169 cases (72%), were the predominant pathogens. Most of the virus infections [164 (69%) of the patients] were of rotavirus and 80% of these were in children under 2 years of age. Rotavirus infection was most prevalent in the cold months. Astrovirus and calicivirus were observed for the first time in the Philippines. Entero-invasive Escherichia coli (13% of patients), Salmonellae (6%) and Shigellae (3.4%) were the commonest bacterial enteropathogens. Cryptosporidium was detected in only six patients. Fever and vomiting, although significantly more prevalent in cases of bacterial diarrhoea than in viral, were not sufficiently sensitive or specific to be used to distinguish the two forms of diarrhoea. Presence of faecal leucocytes (> 5/higher-power field) proved highly sensitive (90%) and specific (84%) in detecting bacteria diarrhoea but reliance on this sign alone would have led to the misdiagnosis of one third of bacterial diarrhoeas. PMID- 8192517 TI - Meningococcal disease in Malawi: studies on the genetic relatedness of the bacteria. AB - Seventy-seven meningococci, isolated from patients and carriers during a large epidemic of meningococcal meningitis in Malawi, were characterized in terms of antimicrobial susceptibility, plasmid content and multi-locus enzyme electrophoresis (MLEE). All the isolates were sensitive to chloramphenicol but six had high enough minimum inhibitory concentrations of penicillin (> or = 2 mg/litre) to render them clinically resistant. Only one isolate was sensitive to sulphonamides but all the isolates were sensitive to rifampicin and ciprofloxacin, two drugs that would be suitable alternatives in prophylaxis. None of the isolates carried plasmids. MLEE indicated that 32 (80%) of the cerebrospinal fluid isolates and 22 (69%) of those from carriers were closely related genetically (in two electropherotypes that differed at only one allele). The Malawian group A meningococci differed from three Ethiopian isolates by two or three alleles, indicating that direct spread from the sub-Saharan meningitis belt to Malawi was unlikely. PMID- 8192518 TI - Vector competence of Simulium metallicum s.l. (Diptera: Simuliidae) in two endemic areas of human onchocerciasis in northern Venezuela. AB - Experimental infections of Simulium metallicum s.l. with Onchocerca volvulus were carried out in two onchocerciasis foci, Altamira and Trincheras, in northern Venezuela, to determine vector competence. Wild-caught flies, fed on infected volunteers, were maintained in the laboratory for 13-15 days at 27 degrees C. Parasite development was complete but asynchronous and retarded. No differences in the vector competence of the two populations of S. metallicum s.l. were found. However, a less efficient development of the parasite occurred during the dry season at both localities. The distribution of the parasite within the vector was aggregated and also displayed seasonal variation. The seasonal susceptibility may be a consequence of a density-dependence regulation mechanism of the parasite within the vector. These results indicate a relatively low vector competence for S. metallicum s.l. in northern Venezuela. PMID- 8192519 TI - Knock down and survival of tsetse flies fed on cattle and pigs dipped in deltamethrin. AB - Glossina morsitans, G. pallidipes and G. fuscipes fuscipes were fed on cattle or pigs that had been dipped in 0.00375% deltamethrin in water, 0-31 days previously. The knock down and survival of the tsetse were then followed in the laboratory. Although mortality was generally less the longer after the dip the flies were fed, all those that fed on the animals within 7 days of the dipping were killed and all those that fed within 21 days were at least knocked down. Glossina morsitans was slightly more susceptible than the other two species tested. PMID- 8192520 TI - T lymphocyte-dependent development of cerebral symptoms in WM/Ms rats infected with Plasmodium berghei. PMID- 8192521 TI - Relapse of Trypanosoma congolense infection in goats after diminazene aceturate is not a result of invasion of the central nervous system. PMID- 8192522 TI - Prevalence of IgG antibodies against Toxoplasma gondii in human sera from Dhofar, Oman. PMID- 8192523 TI - Efficacy of ivermectin treatment of Loa loa filariasis patients without microfilaraemias. PMID- 8192524 TI - Comparative efficacy of four methods for the detection of Strongyloides stercoralis in human stool specimens. PMID- 8192525 TI - Hepatitis C in remote populations of southern Cameroon. PMID- 8192526 TI - Scorpion stings in Jordan. PMID- 8192527 TI - Erythropoietin treatment in patients on maintenance haemodialysis in dialysis centers of South-East region of Poland--present state. AB - South-East region of Poland includes six voivodeships, with about 3.6 mln of inhabitants. Nine dialysis centers work in this region with 273 places to perform maintenance haemodialysis outside Lublin, and 53 places in Lublin Clinic Center. The aim of this paper was to analyse the state of r-Hu EPO treatment in chronic dialysis patients. We would like to compare the treatment possibilities in the clinic unit with other haemodialysis units of our region and with data from Western Europe that we know from EDTA report. Simultaneously we decided to estimate real possibilities of iron treatment monitoring. As it is well known correct management of iron supplementation treatment, allows for the significant reduction of r-Hu EPO administration. PMID- 8192528 TI - Importance of iron status monitoring during erythropoietin treatment in uremic predialysis patients. AB - Since recombinant human erythropoietin (r-Hu EPO) has been introduced to the treatment of anemia in uremic patients the issue of optimal therapy appeared. For proper erythropoiesis not only erythropoietin but also iron, folic acid and B12 vitamin are needed. Iron deficiency is one of the most common factors causing resistance to r-Hu EPO in uremic patients, so its recognition and eventual supplementation is required for optimal hemopoietic response. The aim of presented study, besides monitoring hematological changes, was to measure iron status parameters such as iron, transferrin, ferritin and percentage of hypochromic erythrocytes and estimation of their usefulness in monitoring iron deficiency during r-Hu EPO treatment. PMID- 8192529 TI - Effect of recombinant human erythropoietin (r-Hu EPO) therapy on blood pressure in dialysis patients. PMID- 8192530 TI - Recombinant human erythropoietin administration improves thiamine content in blood and erythrocytes transketolase activity in pre-dialyzed patients. AB - Recombinant human erythropoietin (r-Hu EPO) has proved to be effective in correcting anemia of dialyzed patients. Since 1987 reports have been published announcing the introduction of this hormone to the treatment of anemia in pre dialyzed patients, too. Besides successful correction of anemia no evidence of acceleration of the progression of renal failure has been noted. The question of whether r-Hu EPO can also correct metabolic disturbances in predialyzed patients is to be answered. These metabolic disturbances comprises, among others, the decrease in thiamine content in blood and the deterioration of erythrocytes transketolase activity (ETKA) we described in another paper. However, as to the present we did not notice any publication concerning the impact, of r-Hu EPO administration on thiamine content in blood and on the ETKA. The purpose of our study was therefore to determine the influence of r-Hu EPO therapy in pre dialyzed patients on thiamine level in plasma and erythrocytes and on the ETKA. Additionally, we wanted to answer the question if there was any parallel change in hematocrit index, thiamine level in blood and the ETKA in patients we observed during r-Hu EPO therapy. PMID- 8192531 TI - Human recombinant erythropoietin: progress in clinical development. PMID- 8192532 TI - Peritoneal dialysis adequacy during the r-Hu EPO treatment. AB - The dialysis adequacy was considered as the treatment method which eradicated the symptoms and signs of uremia and led to the full rehabilitation of treated patients. The chronic renal failure patients substitutional treatment using both peritoneal dialysis and hemodialysis assures correction of biochemical disturbances but only 33% of dialyzed patients are fully rehabilitated. Such situation is caused by the uremic anemia. The erythropoietin deficit is the main reason of the uremic anemia. The clinical effects of the erythropoietin treatment in hemodialyzed, peritoneal dialyzed and pre-dialyzed patients were proved. The erythrocytes increment to the normal or almost normal levels may caused the dialysis kinetics changes. During the r-Hu EPO treatment in both hemodialyzed and peritoneal dialyzed patients the dialysis effectiveness changes occurred. The dialysis therapy adequacy is mainly caused by the dialysis efficiency and additionally by the residual renal function and metabolism state. Taking into account own peritoneal dialysis kinetics parameters research results during the r Hu EPO treatment the dialysis adequacy was evaluated. The aim of this study was the optimal dialysis scheme definition when the peritoneal transfer changes occurred as the r-Hu EPO treatment effect. PMID- 8192533 TI - The effect of recombinant human erythropoietin (r-Hu EPO) administration on the blood chemistries and composition in uremic rats. AB - Recombinant human erythropoietin (r-Hu EPO) therapy improves the anaemia of patients on chronic hemodialysis, on peritoneal dialysis and those with chronic renal failure who have not yet started any form of renal replacement therapy. In the last category there is concern that r-Hu EPO therapy may be associated with deterioration of the reserve renal function. But new data showed that even during more prolonged treatment the correction of anaemia does not have a major detrimental effect on renal function. The study was undertaken to examine the influence of r-Hu EPO therapy on renal function and rheological erythrocytes finding in uremic rats. PMID- 8192534 TI - The effect of subcutaneous recombinant human erythropoietin (r-Hu EPO) in CAPD patients with renal anaemia. AB - Several factors may contribute to the pathogenesis of uraemic anaemia but there is general agreement that inadequate secretion of erythropoietin is the main cause. Recombinant human erythropoietin (r-Hu EPO) is today widely used in the treatment of patients with renal anaemia. Initial studies were conducted on patients receiving haemodialysis (HD) using intravenous dosing, and number of reports have confirmed the efficacy and safety of the hormone. However, there is still limited information on the use of r-Hu EPO in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The cost of this treatment was initially very high. The optimal way of administration of the drug and optimal dosage is still under discussion. More studies are needed to optimize treatment from a clinical as well as an economic point of view. We therefore present our result on the efficacy and safety of low dose r-Hu EPO given subcutaneously in th treatment of anemia in CAPD patients. PMID- 8192535 TI - Influence of long-term erythropoietin treatment on plasma levels of calcium phosphate related hormones in haemodialyzed uraemic patients. AB - Exacerbation of secondary hyperparathyroidism (as manifested by calcium deposits and local inflammation in periarticular tissues) has been reported in haemodialyzed (HD) uraemic patients treated with recombinant human erythropoietin. However, short-term treatment with recombinant human erythropoietin (r-Hu EPO) did not influence significantly plasma levels of parathyroid hormone (PTH), calcitonin (CT) and 25-hydroxycholecalciferol (25 OHD3) in uraemic HD patients. The present study aimed to assess the effect of long-term r-Hu EPO therapy for 12 months on plasma PTH, CT, 25-OHD3 and 1,25 dihydroxycholecalciferol (1,25-(OH)2D3) in uraemic HD patients. PMID- 8192536 TI - [History of a cutaneous lesion: chromomycosis]. AB - A modern approach of Pathology, using immunohistochemistry, electron microscopy and image analysis, was made to describe the matrix profile of the non reversible fibrosis observed in the cutaneous lesion of Chromomycosis. The distribution pattern of cell populations in dense inflammatory infiltrate, sometimes organized in granulomas, has been identified concurrently with the in situ demonstration of the pro-fibrotic cytokine TGF-beta. The professional phagocytes (polymorphonuclear neutrophils and macrophages) seem unable to fully eliminate the fungi. We suppose it is this persistence which explains the exuberant cell immune response. PMID- 8192537 TI - [Clinical epidemiology of plague in Madagascar (current data)]. AB - After a recall of the epidemiological cycle of plague, the authors describe the course of this disease from 1989 to 1992. Out of 2676 pathological samples suspected of plague, 2105 biological examinations were carried out. 312 cases were confirmed and 335 considered as probable. 93% of those positive cases come from the plague triangle located in the Central Highlands and delimited by Ambatondrazaka, Miarinarivo and Fianarantsoa and they occur during the rainy season (November to March). However, an outbreak of urban epidemics is possible on the coast during the cold season. The most frequent clinical form had been bubonic plague (90%). Plague did not much concern young children and men are affected more often than women. Clinically, toxi-infectious syndrome, lymph node reaction and hemoptoic spits can be noted. The 1989-1992 results are compared with those of the two previous studies. PMID- 8192538 TI - [Schistosoma mansoni morbidity in a region of the south of Madagascar: preliminary data]. AB - "Schistosoma mansoni morbidity in a Southern region of Madagascar: preliminary data". The prospective study of the schistosomiasis mansoni morbidity among the practice of a medical and surgical hospital located at Sakalalina, a village of the southern foot-hills of the malagasy Highlands, allowed to record a prevalence rate of 5.45%. PMID- 8192539 TI - [Epidemiological data on children hospitalized with malaria from 1983 to 1992]. AB - Authors record the manifestations on the child of the severe malaria epidemic that raged in Antananarivo. Using the hospitalisation registers of the Debre room, Pediatric Service "A", at the Hospital of Befelatanana as source documents, they underline some points: Concerning morbidity, the epidemic started in 1984, reached its highest point in 1988 (26.7%, of in patients) and began to fade away in 1992. Boys and girls were equally affected, with a majority among children of 5 years old and more (51 to 58% of cases). All patients came from the center of Antananarivo (33.5%) or mainly from the surroundings (66.5%). At the highest point of the epidemic, about half of the children were suffering from severe malaria (48.9%). Plasmodium falciparum was the parasite responsible for 93.3% of cases. It seems that mortality is not influenced by sex, age or home but two factors are especially observed: nutrition disorders and delay of hospitalisation. The quinine based treatment has stemmed mortality by neuropaludism since two years. PMID- 8192540 TI - [Epidemiological malaria surveillance in 3 villages of the Madagascar highlands]. AB - Results of the epidemiological surveillance of falciparum malaria carried out since 1987 in three villages of the malagasy Highlands are reported. They clearly show the unsteady endemo-epidemic characteristic of the disease with highly variable transmission levels according to foci. At Manarintsoa, a south-western village 20km away from the Capital, the disease has now fully disappeared after the ravage of 1986. But it might reappear with new imported cases and by lack of antivectorial measures. Although Anopheles arabiensis had been rare and its aggressivity rate weak (0.91-2 infecting bites per year per man), surveillance is indispensable for the future. An Ankazobe and Mahavelona, two north-western localities respectively 100km and 65km away from Antananarivo, malaria is endemic with periodic outbreaks during rainy season. At Ankazobe, Anopheles funestus is the main vector maintaining endemic in this area while the role of Anopheles gambiae l.s. is only secondary. At Mahavelona, because of the weak presence of vectors, the treatment protocol by Quinimax has been applied in order to study transmission. This study obviously shows that contrary to set ideas in the Highlands, backward transmission is possible up to the first months of the austral winter (June-July). In these two last villages, adults have acquired some premunition. PMID- 8192541 TI - [Situation of endemic rabies in Madagascar]. AB - The course of endemic rabies in Madagascar between 1982 and 1991 is related. Rabies has been raging over the whole island and dog is essentially affected, constituting the single vector of human rabies cases. The authors recall the main measures of struggle against rabies. PMID- 8192542 TI - [Epidemiological stratification of malaria in Madagascar]. AB - Madagascar is considered as a sub-region of the Afrotropical geographical Region in spite of the high endemicity of 95% of the invertebrates. Nevertheless the three malaria vectors An. gambiae s.s., An. arabiensis and An. funestus are quite similar to those of the continental Africa. This support the hypothesis of their recent introduction. Plasmodium falciparum is the dominant parasite but the prevalence of P. vivax is not negligible. It is linked to the Asian component of the human population. P. malariae and P. ovale are of minor importance. The main epidemiological "facies" of Africa are found in Madagascar. The equatorial facies on the East Coast is characterized by a high transmission all year long. In the tropical facies on the West Coast transmission is seasonal (7 months at least). In both areas, malaria is stable and the inhabitants acquire a high immunity before the age of ten; most of the severe cases touch children below 10. The three vectors can be found but An. gambiae s.s. is dominant. In the exophilic southern facies the transmission is seasonal (two to four months). The only vector is An. arabiensis. Malaria is unstable and severe epidemics occur during the years of high rainfall. All age groups are vulnerable because the population is not immune in the Plateaux facies above 1,000 m., malaria is unstable. Severe epidemics occurred in 1987-1988. The vectors are An. Arabiensis and An. funestus. The occurrence of P. falciparum on the Plateaux seems linked to the development of irrigation of rice farming in the XIXth century. Most of the anopheles breeding places on the Plateaux are dependent on rice cultivation. Urban development has brought the inhabitants of the suburbs in close contact with rice fields. Despite the high number of anopheline bites the number of malaria cases remains by far lower than in the neighbouring rural areas. Regional migrations inside the island bring non-immune populations, from the south and the plateaux, in highly malarious areas of the coast, where the migrants are exposed to high risk. In spite of 40 years of uncontrolled use, chloroquine can still cure most, if not all, of malaria cases. Control measures appropriated to the different areas of Madagascar are discussed. PMID- 8192543 TI - [Aspects of Plasmodium falciparum sensitivity to chloroquine in Madagascar from 1982 to 1993]. AB - According to pharmaco-sensitivity studies, about 20% of local Plasmodium falciparum strains showed a certain degree of resistance to chloroquine. No resistance of R3 type has never been observed. During this whole period, the decrease of sensitivity phenomenon remains stable. Because of its remarkable action on parasitemia and fever, chloroquine remains the best antimalaria in simple malarial attacks in madagascar. PMID- 8192544 TI - [Anemia among schoolchildren 5 to 14 years old in Sainte Marie (Madagascar)]. AB - The Island of Sainte Marie is located at 6 km from the Eastern Coast of Madagascar. The climate is a muggy tropical one, with an average temperature rising above 20 degrees C all along the year and precipitations superior to 2500 mm. In 1990, a clinical surveillance of ten affections has been performed by every health units of the Island: paludal syndromes, nutrition disorders and anemia have been the focus of symptomatic definition. Blood samples have been taken from 100 pupils of the village of Ambodiforaha for hemogram determination and research of malaria hematozoon. Four pupils out of five show biological anemia, more than 10% suffer from acute anemia (less than 3.5 millions of red blood cells for each microliters, hematocrit inferior to 30, less than 9 g of hemoglobin for 100 ml). 87% suffer from nutritional anemia, 17% from iron deficient anemia. Those figures cannot be found in health statistics. There is a high rate of nutritional and iron deficient anemia, but the problem is not well perceived or not at all by the health system. Anemia must be related to the strength of paludal transmission, to the importance of nutrition disorders and the prevalence of intestinal parasitosis. A better knowledge of the epidemiology of anemias and their morbid consequences would allow the setting of a prevention programme useful for children under 5 years and for pregnant women. PMID- 8192545 TI - [Autoperfusion of ascitic fluid: 38 cases]. AB - "38 observations of reperfusion of ascitic fluid ". In this study, the authors report their experiences of paracentesis associated with the perfusion or the reperfusion of the sick's own ascitic fluid in the treatment of tense ascite determined mostly by Schistosomiasis mansoni. PMID- 8192546 TI - [Influenza surveillance in Tananarive during the year 1992]. AB - The authors relate the 1992 results of influenza surveillance in Antananarivo. 24 influenza virus A (H3N2) strains were isolated from 467 pharyngeal swabs. The virus had been continually spreading from January to September, with a peak in July, along with some monthly sporadic isolations. The highest respiratory morbidity was observed in June and July. The collection processes of influenzal and respiratory morbidity statistics are also discussed in order to standardize data and to define the real impact of influenza and other acute affections of respiratory tracts on the population. PMID- 8192547 TI - Mental illness in the biological and adoptive relatives of schizophrenic adoptees. Replication of the Copenhagen Study in the rest of Denmark. AB - BACKGROUND: Our previous investigation of the prevalence of mental illness among the biological and adoptive relatives of schizophrenic adoptees in Copenhagen, Denmark, showed a significant concentration of chronic schizophrenia (5.6%) and what Bleuler called "latent schizophrenia" (14.8%) in the biological relatives of chronic schizophrenic adoptees, indicating the operation of heritable factors in the liability for schizophrenic illness. METHODS: We now report the results of a replication of that study in the rest of Denmark (the "Provincial Sample"). RESULTS: In this sample, the corresponding prevalences were 4.7% and 8.2%. In the combined "National Sample" of adoptees with chronic schizophrenia, that disorder was found exclusively in their biological relatives and its prevalence overall was 10 times greater than that in the biological relatives of controls. CONCLUSIONS: This study and its confirmation of previous results in the Copenhagen Study speak for a syndrome that can be reliably recognized in which genetic factors play a significant etiologic role. These findings provide important and necessary support for the assumption often made in family studies: observed familial clustering in schizophrenia is an expression of shared genetic factors. PMID- 8192548 TI - Independent diagnoses of adoptees and relatives as defined by DSM-III in the provincial and national samples of the Danish Adoption Study of Schizophrenia. AB - BACKGROUND: This report describes the independent application of DSM-III criteria to the adoptees and relatives in the Provincial sample of the Danish Adoption Study of Schizophrenia of Kety and colleagues. We report these results and combine them with those reported previously for the Copenhagen sample to form the National sample. METHODS: Personal interviews and institutional record summaries of adoptees and biological and adoptive relatives were "blindly" diagnosed using DSM-III criteria. "Schizophrenia spectrum" was a priori defined as schizophrenia; schizoaffective disorder, mainly schizophrenic subtype; and schizotypal and paranoid personality disorders. RESULTS AND CONCLUSION: In the Provincial sample, the prevalence of "spectrum" disorders was significantly greater in biological relatives of schizophrenia spectrum vs control adoptees. The results were also consistent with the genetic transmission of individual diagnoses within the spectrum. When combined into the National sample, the results provided strong evidence for (1) the genetic transmission of DSM-III schizophrenia; (2) a genetic relationship between DSM-III schizophrenia, mainly schizophrenic schizoaffective disorder, and schizotypal personality disorder; and (3) the absence of a significant genetic relationship between the schizophrenia spectrum and either psychotic nonspectrum disorders, major depression, or anxiety disorders. We found no evidence for the familial environment transmission of schizophrenia spectrum disorders. These results are consistent with the findings reported by Kety and coworkers from their diagnostic review. PMID- 8192549 TI - Neuropsychological deficits in schizophrenics. Relationship to age, chronicity, and dementia. AB - BACKGROUND: We sought to determine whether neuropsychological impairment in schizophrenia is related to current age, age at onset, or duration of illness, and whether the pattern of such impairment can be distinguished from that caused by progressive dementias of Alzheimer's type. We administered a comprehensive neuropsychological test battery to a normal control group (n = 38), a group of ambulatory patients with Alzheimer's disease (n = 42), and three ambulatory schizophrenic groups: early onset-young (n = 85), early onset-old (n = 35), and late onset (n = 22). Tests were grouped and analyzed according to eight major ability areas, and published procedures were used to remove the expected effects of normal aging. RESULTS: The three schizophrenic groups were found to be neuropsychologically similar to one another and different from normal controls and patients with Alzheimer's disease. There were no significant differences among the schizophrenic groups in level or pattern of neuropsychological functioning. Patients with Alzheimer's disease demonstrated less efficient learning and particularly more rapid forgetting than did the other groups. CONCLUSIONS: These findings suggest that neuropsychological impairment in schizophrenia is unrelated to current age, age at onset, or duration of illness. The study further suggests that the encephalopathy associated with schizophrenia is essentially nonprogressive and produces a pattern of deficits that is different from that seen in progressive cortical dementias. PMID- 8192550 TI - Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood. AB - BACKGROUND: A previous study demonstrated that myelination of the superior medullary lamina along the surface of the parahippocampal gyrus is occurring in human brain during adolescence. To further investigate whether postnatal increases of myelination may continue during the second decade and possibly even longer, the extent of myelination in this region has been analyzed in 164 psychiatrically normal individuals aged newborn to 76 years. METHODS: Cross sections of the hippocampal formation with adjoining hippocampal gyrus were analyzed on a blinded basis using either a global rating scale or measurements of the area of myelin staining. RESULTS: A curvilinear increase in the extent of myelination between the first and sixth decades of life (r = .71 and r = .67, respectively) was observed. When the area of myelination was expressed relative to brain weight, there was a twofold increase between the first and second decades and an additional increase of 60% between the fourth and sixth decades. Female subjects showed a significantly greater degree of myelin staining than did male subjects during the interval of ages 6 to 29 years; however, after the third decade, there were no gender differences in the area of myelin staining. CONCLUSIONS: The increased staining of myelin during the first and second decades principally occurred in the subicular region and adjacent portions of the presubiculum. During the fourth through sixth decades, however, it extended to progressively more lateral locations along the surface of the presubiculum. The precise origin(s) of the axons showing progressive myelination is unknown; however, the axons in the subiculum may include some perforant path fibers, while those found in the presubiculum may include cingulum bundle projections. Overall, our data are consistent with the idea that both early and late postnatal increases of myelination occur in a key corticolimbic relay area of the human brain and underscore the importance of applying a neurodevelopmental perspective to the study of psychopathology during childhood, adolescence, and even adulthood. PMID- 8192551 TI - The panicogenic effects of cholecystokinin-tetrapeptide are antagonized by L 365,260, a central cholecystokinin receptor antagonist, in patients with panic disorder. AB - BACKGROUND: We investigated whether the selective brain cholecystokinin (CCKB) receptor antagonist, L-365,260, could antagonize the panicogenic effects of CCK tetrapeptide (CCK-4) in patients with panic disorder. DESIGN: The study employed a double-blind, placebo-controlled, two-period crossover design. Patients (N = 29) received a single oral dose of L-365,260 (10 or 50 mg) or placebo 90 minutes prior to injection of CCK-4. After a 1-week washout period, patients received a different dose of L-365,260 or placebo according to a balanced incomplete block design. RESULTS: The 50-mg dose of L-365,260 was superior to placebo in reducing the number (P < .01) and sum intensity (P < .001) of symptoms induced with CCK-4. Panic attack frequency following CCK-4 injection was 88% for patients receiving placebo, 33% for those receiving the 10-mg dose, and 0% for those receiving the 50-mg dose. The difference between the effects of the 50-mg dose and placebo was statistically significant (P = .002). Increases in heart rate following CCK-4 injection were markedly reduced with both the 50-mg (P < .0001) and 10-mg (P < .01) doses compared with placebo. CONCLUSION: These data suggest that CCKB receptors are an important site of action of exogenous CCK-4. It will be important to determine in future studies the efficacy of CCKB receptor antagonists as antipanic agents. PMID- 8192553 TI - Lithium prophylaxis in American patients with unipolar disorder. PMID- 8192552 TI - Increased density of guanine nucleotide-binding proteins in the postmortem brains of heroin addicts. AB - OBJECTIVE: To directly evaluate the guanine nucleotide-binding (G) protein subunits alpha, beta, and gamma, which are involved in the signal transduction of opioid receptors, in the postmortem brains of heroin addicts who had died of an opiate overdose. METHODS: Specimens of the frontal cortex (Brodmann's area 9) were collected from 11 heroin addicts and 10 control subjects without a history of drug abuse. The biochemical status of human brain G protein subunits during opiate dependence was studied by means of immunoblotting techniques. Solubilized G proteins were separated by gel electrophoresis, transferred to pyroxylin membranes (western blotting) labeled with specific antiserum samples, and quantitated by image analysis after enhanced chemoluminescence. RESULTS: In the frontal cortex, relevant increases in the immunoreactivities of G alpha i 1/2 (19% +/- 4%, P < .005), G alpha o (29% +/- 7%, P < .005), and G alpha s (26% +/- 5%, P < .005) but not of G alpha i3 were found in heroin addicts compared with age- and sex-matched controls. Moreover, the amount of G protein beta-subunit immunoreactivity was also consistently increased (27% +/- 8%, P < .01) compared with controls in the same brain region. These G protein changes in the brains of human opiate addicts paralleled (with the exception of G alpha s) those obtained in the brains of morphine hydrochloride-dependent rats. The increase in G alpha s immunoreactivity that was observed in the rat brain only after the short-term morphine administration (24% +/- 3%, P < .005) suggests that the increase in G alpha s immunoreactivity in the brains of human addicts could be the cellular response to a deadly overdose of heroin. CONCLUSIONS: Alterations in the density of specific Gi and Go protein subunits that are coupled to mu-opioid and other opioid receptors may be of clinical relevance in opiate tolerance, dependence, and abstinence syndrome. PMID- 8192554 TI - Maintenance therapy in depression. PMID- 8192555 TI - Klein's suffocation theory of panic. PMID- 8192556 TI - Clinical pathology residency training. The need for reform. PMID- 8192557 TI - Clinicopathologic correlations of antiphospholipid antibodies. An autopsy study. AB - The clinicopathologic correlations of antiphospholipid antibodies (aPLs) have so far only been examined in case reports and highly selected series. This study assessed the incidence of aPLs in 156 consecutive, unselected autopsies and correlated the pathological findings with the clinical histories. Elevations of aPLs were found in 20.5% of the autopsy population, compared with 9.6% of age- and sex-matched controls and 2% of healthy normal subjects. There was a higher incidence of thromboembolic disease in patients with elevated aPL levels compared with those without, but the histology of thrombi was similar in both groups, with no evidence of vasculitis in the aPL-positive individuals. Patients with transient ischemic attacks and cardiac valve lesions had a high incidence of aPLs, as reported previously. Five cases that fit the designation of primary antiphospolipid antibody syndrome were noted. The study concludes that aPLs are relatively common in a hospital autopsy population and are commonly associated with thromboembolic events, that the thromboemboli are not associated with vasculitis, and that primary aPL syndrome is more common than generally appreciated. PMID- 8192558 TI - Short-term, within-person variability in clinical chemistry test results. Experience from the Atherosclerosis Risk in Communities Study. AB - We report the within-person, between-person, and methodological variances of a number of chemical analytes for free-living, middle-aged adults who participated in the Atherosclerosis Risk in Communities Study's Intraindividual Variability Study. The Atherosclerosis Risk in Communities Study is a National Institutes of Health-sponsored multicenter study of atherosclerotic risk factors. In the Atherosclerosis Risk in Communities Study and its Intraindividual Variability Study, concentrations of the following 12 chemical analytes were measured in serum from fasting individuals: sodium, calcium, potassium, creatinine, albumin, total protein, magnesium, phosphorus, urea, insulin, glucose, and urate. The analytes are listed in order of the increasing reliability coefficient (ie, the fraction that between-person variance represents of the total observed population variance), which ranged from .59 for sodium to .91 for urate. The reliability coefficient is a strong predictor of the possibility of finding statistical correlations between measured analyte concentrations and disease occurrence in an epidemiological study like the Atherosclerosis Risk in Communities Study. The within-person variance and methodological variance are also useful in computing confidence intervals for sequential laboratory test results in patients and evaluating limits for internal quality control and proficiency testing programs. PMID- 8192559 TI - Implementation of a proficiency testing program for Lyme disease in New York State. AB - Nine proficiency test events for Lyme disease (Borrelia burgdorferi) antibody were carried out from October 1988 to January 1992 by the New York State Department of Health, Albany, Overall sensitivity for the 846 participants averaged 95.4%, with varying sensitivities of 98.7% for users (71 laboratories) of immunofluorescence assays, 97.4% for users (144 laboratories) of solid-phase fluorescence immunoassays, and 94.6% for users (631 laboratories) of enzyme immunoassays. Thirty percent of the enzyme immunoassay laboratories tested at greater than or equal to 98.4% sensitivity by the DiaMedix test kit (DiaMedix Corp, Miami, Fla) and MarDx test kit (MarDx Diagnostics Inc, Scotch Plains, NJ), while 7% tested at less than or equal to 83% by the Access test kit (Access Medical Systems Inc, Branford, Conn) and the Cambridge BioScience test kit (Cambridge BioScience, Worcester, Mass). Overall specificity was 98.8%, with specificities greater than 99% for both solid-phase fluorescence immunoassay and enzyme immunoassay users and 92.9% for immunofluorescence assay users. Cross reactivity with Treponema pallidum antibody was high for the Hillcrest (Hillcrest Biologicals, Cypress, Calif) (30%) and Wampole (Wampole Laboratories, Cranbury, NJ) (25%) immunofluorescence assay test kit users and for the MarDx (30%) and 3M (3M Diagnostics Systems Inc, Santa Clara, Calif) (24%) enzyme immunoassay test kit users. Laboratories that tested by the Wampole immunofluorescence assay test kit had also high cross-reactivity (25%) against heterophile antibody. PMID- 8192560 TI - Black cartilage after therapy with levodopa and methyldopa. AB - A study was undertaken of 14 autopsy cases with pigmented rib cartilage. Twelve of these patients had been treated with levodopa because of Parkinson's disease for at least 6 years, and two had been treated with methyldopa because of essential hypertension for 19 years. Thirty-two percent of the autopsy cases of Parkinson's disease during a recent 70-month period demonstrated pigmented rib cartilage. Only one of them also demonstrated pigmentation of intervertebral disks. No abnormal pigmentation was seen in other sites. The pigment was located in the hyaline matrix of rib cartilage and in necrotic chondrocytes. Levodopa was chromatographically demonstrated within the cartilage of patients with Parkinson's disease, but in both pigmented and unpigmented sites. It is speculated that a pigmented drug metabolite is bound preferentially to the matrix of rib cartilage. Dopa pigmentation only occurs in cartilage and differs in several respects from endogenous and exogenous ochronosis. It appears to be harmless but irreversible. PMID- 8192561 TI - Abnormal pulmonary macrophages in lysinuric protein intolerance. Ultrastructural, morphometric, and x-ray microanalytic study. AB - Pediatric patients with lysinuric protein intolerance are predisposed to develop alveolar hemorrhage and pulmonary alveolar proteinosis. We evaluated the ultrastructural features of pulmonary alveolar proteinosis and the potential abnormality of pulmonary macrophages in lysinuric protein intolerance. Lung tissue specimens obtained at autopsy were examined by transmission electron microscopy. Pulmonary macrophages from bronchoalveolar lavages were studied by electron microscopy, morphometry, and x-ray microanalysis and compared with control cells. The macrophages of patients with lysinuric protein intolerance contained significantly more multilamellar structures than did control cells and showed electron-dense material identified to contain excess iron. The predisposition to develop alveolar proteinosis and the abnormal ultrastructure of pulmonary macrophages suggest altered phospholipid metabolism in patients with lysinuric protein intolerance. The marked intramacrophageal accumulations of iron might indicate altered iron metabolism or subclinical hemorrhages in lung tissue. PMID- 8192562 TI - Pulmonary hemorrhage. A fatal manifestation in IgA nephropathy. AB - Two patients with asymptomatic IgA nephropathy (IgAN) and a third patient with chronic renal failure due to IgAN died following a recent onset of dyspnea, hemoptysis, and pulmonary infiltrates. In all cases, the cause of death was respiratory failure attributed to either bronchopneumonia or pulmonary edema. However, no infectious agent was identified. In all three patients, the diagnoses of IgAN and idiopathic pulmonary hemorrhage were established at postmortem examination. Acute alveolar hemorrhage was present in two patients. All three patients had heavy alveolar hemosiderin-laden macrophages, and capillaritis was recognized in two of them. The occurrence of fatal pulmonary hemorrhage in patients with IgAN is rare. Our findings suggested an immune complex-mediated pulmonary injury that was possibly related to the systemic nature of IgAN. PMID- 8192563 TI - Primary gastric T-cell lymphoma. Morphological and immunohistochemical studies of two cases. AB - Primary T-cell lymphoma of the stomach is very rare. We report two cases of primary gastric T-cell lymphoma, one of which had a morphological appearance and a phenotype that were similar to those of node-based peripheral T-cell lymphoma. The other case was related to human T-cell lymphotropic virus type I and displayed a feature of lymphoma cell pleomorphism. The lymphoma cells were both positive for Ki-1/CD30. PMID- 8192564 TI - Malignant acoustic schwannoma. AB - An unusual pleomorphic tumor was resected from the cerebellopontine angle of a 40 year-old man with no stigmata of neurofibromatosis. The tumor showed multinucleated giant cells scattered amid smaller, slightly elongated cells. The tumor showed a rudimentary fascicular pattern containing some looser areas but no nuclear palisading. A diagnosis of Schwann cell tumor was made based on ultrastructural findings and on immunoreactivity for S100 protein. Malignancy was suggested by the extreme pleomorphism of the tumor, by the presence of tripolar mitotic figures, and by flow cytometric demonstration of aneuploidy and of a significant proportion of S-phase tetraploid nuclei (9%). Ten months after the first operation, the tumor had regrown to its original size, and was again resected. The histologic and ultrastructural appearances were similar to those of the first specimen, but flow cytometric analysis now showed a double aneuploid population of nuclei and showed 12% of the nuclei in tetraploid S phase. Within 11 months of the second operation, the tumor had regrown to an estimated size of 22 cm3. Four months of radiotherapy subsequently halted tumor growth, but additional lesions appeared in the cervical and high thoracic areas. PMID- 8192565 TI - Prolactin-producing pituitary adenoma in a male-to-female transsexual patient with protracted estrogen administration. A morphologic study. AB - Pituitary adenoma developed in a 33-year-old male-to-female transsexual patient who was given estrogen, starting at 16 years of age; the pituitary adenoma was surgically removed and studied by light microscopy, immunocytochemistry, and in situ hybridization. The adenoma cells were immunoreactive for prolactin, and exhibited a strong signal for prolactin and estrogen receptor messenger RNAs and a weak signal for dopamine receptor messenger RNA. The question of whether the development of an adenoma was incidental or was the direct effect of estrogen or whether it was mediated via other mechanisms, such as activation of growth factors or oncogenes or inhibition of tumor-suppressing genes or other genetic abnormalities, remained unresolved. The present case, which, to our knowledge, is the first to describe structural findings of a pituitary adenoma in a transsexual patient who was given estrogen, reinforces the view that protracted stimulation may play a role in the genesis of endocrine tumors. PMID- 8192566 TI - Fatal disseminated herpesvirus infection with hepatitis. A peritoneal fluid cytologic warning. AB - A 19-year-old man died of a disseminated herpesvirus infection. Microscopic examination of a peritoneal fluid specimen revealed cellular changes characteristic of a herpetic process, and an autopsy confirmed widespread herpes simplex virus type II infection. Viral infections may be diagnosed by cytologic examination of body fluid specimens. PMID- 8192567 TI - Ductal adenocarcinoma arising in a heterotopic pancreas situated in a hiatal hernia. AB - We present a case of ductal adenocarcinoma originating in a heterotopic pancreas in a 60-year-old patient. The tumor developed at the esophagogastric junction in a hiatal hernia. The nontumoral pancreatic tissue showed ductal cystic dystrophy with enclosed stones, as well as lesions of chronic pancreatitis with metaplastic changes. The perigastric lymph nodes and the liver contained metastatic deposits. Malignant transformation in an ectopic pancreas is exceptional. To our knowledge, this would be the first case occurring in such a location. We review the literature on the subject and discuss the theory of the tumors arising in an aberrant pancreas. PMID- 8192568 TI - A case of primary cystic mediastinal hemangiopericytoma. AB - We describe a 35-year-old man with a primary cystic mediastinal hemangiopericytoma who presented with the complaint of progressive dysphagia for 6 months. The computed tomography and magnetic resonance imaging findings revealed that a well-defined, fluid-filled mass (measuring approximately 10 x 10 cm) was located posterior to the heart and inferior to the carina of the bronchus. Tumor puncture showed translucent yellow fluid with normal concentrations of carcinoembryonic antigen, squamous cell carcinoma-related antigen, and carbohydrate antigen 19-9 and a high concentration of carbohydrate antigen 125. After removal of the tumor, microscopic examination revealed a malignant hemangiopericytoma. To our knowledge, this is the first case of a primary mediastinal hemangiopericytoma with cystic formation. Moreover, we showed the specific biochemical findings of the cystic fluid that were useful for differentiation from other cystic mediastinal tumors. PMID- 8192569 TI - An introductory orientation to clinical pathology core and on-call responsibilities. AB - An introductory 4-week orientation for clinical pathology is described. There were 76 hours of lectures, 74 hours of conferences, and 68 hours of laboratories for a total of 221 hours. During the orientation, all calls handled by the residents were evaluated as to resolution, patient outcome, and interaction required. Eighty calls were received during the orientation from 57 technologists (71%), 16 physicians (20%), and seven nurses (9%). The calls originated concerning the following: blood banking, 37 (46%); hematology, 21 (27%); chemistry, 14 (18%); microbiology, five (6%); and administration, three (4%). Sixty percent of the calls were consultative and 40% were supervisory. Ninety nine percent were handled appropriately by the residents. Patient outcome was moderately or significantly affected in 44% of all calls, divided between 67% of all consultative calls and 9% of all supervisory calls. Significant pathologist interaction was required in 49% of all calls, divided between 71% of the consultative calls and 16% of the supervisory calls. Using this integrated, dynamic system of resident instruction, on-call experience, and evaluation, residents quickly gain confidence in handling call, didactic clinical consultation, and patient management. The orientation and on-call system described provides for a relevant and dynamic system for resident education. PMID- 8192570 TI - Presence and sources of pollutants in the Baltic Sea. PMID- 8192571 TI - Nuclear retinoic acid receptors and regulation of gene expression. PMID- 8192572 TI - The role of retinoids in normal development and retinoid-induced malformations. PMID- 8192573 TI - Retinoid teratogenesis: toxicokinetics and structure-specificity. PMID- 8192574 TI - The neurochemical effects of PCB exposure are age-dependent. PMID- 8192575 TI - Risk estimation and primary prevention of birth defects. PMID- 8192576 TI - The role of mechanistic studies in understanding target organ toxicity. PMID- 8192577 TI - Rational species extrapolation of toxic effects. PMID- 8192578 TI - Predicting the toxic dose or concentration. Is there a difference? PMID- 8192579 TI - The role of investigative toxicology in pharmaceutical industry. AB - In summary, the benefits of a mechanistic toxicology approach include increased understanding of the processes underlying primary pathology, the development of predictive capability, enhanced decision making and improved responsiveness to regulatory agencies. The overall objective of toxicology in the pharmaceutical industry is risk benefit assessment in order to support product registration. This requires both that studies be conducted in accordance with regulatory guidelines and that the biological processes underlying pathology be understood. These should be regarded as inseparable components of the risk assessment process. PMID- 8192580 TI - Metal-induced autoimmunity. PMID- 8192581 TI - Genotoxic effects of metal compounds. PMID- 8192582 TI - The importance of exposure measurements in risk assessment of drugs. PMID- 8192583 TI - Interrelationship between eutrophication and effects of pollutants. PMID- 8192584 TI - The impact of genetic polymorphisms in risk assessment of drugs. PMID- 8192585 TI - Kinetic analysis using positron emission tomography. PMID- 8192586 TI - The application of modelling in toxicokinetics. PMID- 8192587 TI - Alterations in kinetic parameters resulting in modification of toxicity. PMID- 8192588 TI - Importance of genetic alterations in tumour development. PMID- 8192589 TI - Transgenic mouse models in chemical carcinogenesis studies. PMID- 8192590 TI - Cell proliferation and cell death in rat liver carcinogenesis by chemicals. PMID- 8192591 TI - Use of mechanistic and other data in identifying carcinogens: a review based on the IARC Monographs programme. PMID- 8192592 TI - Developmental toxicity--magnitude of the problem. PMID- 8192594 TI - Health problems related to respiratory sensitisation. PMID- 8192593 TI - Ecology of the Baltic--introduction. PMID- 8192595 TI - Effects of toxic metal pollutants on the ecology of the Baltic Sea. PMID- 8192596 TI - Effects of persistent organic pollutants on biota in the Baltic Sea. PMID- 8192597 TI - Human health risk assessment and risk perception related to the Baltic Sea. PMID- 8192598 TI - Test methods for contact sensitization. PMID- 8192599 TI - Test methods for respiratory sensitization. PMID- 8192601 TI - Risk assessment of sensitizing agents. AB - This review describes an approach that has been used to assess the skin sensitization risk of new product ingredients prior to and after marketing. The risk assessment process utilizes a comparative toxicological approach in which data on the inherent toxicity of a material and the exposure to it through manufacturing or consumer use or foreseeable misuse are integrated and compared with data generated by 'benchmark' materials of similar chemistry or product application, or both. This approach has been valuable in providing an accurate assessment of skin sensitization potential and the basis for eventual safe marketing of a wide range of consumer household and personal care products and topical pharmaceuticals. PMID- 8192600 TI - Newer approaches to the evaluation of sensitization phenomena. PMID- 8192602 TI - 90Sr and 137Cs in pilchards from the Adriatic Sea. AB - The biological concentration factors for the system pilchard/sea-water for 90Sr and 137Cs are presented and discussed. The 90Sr concentration factor was constant, whereas the concentration factor for 137Cs steadily increased after the Chernobyl accident. An UNSCEAR model was used to describe 90Sr transfer from fallout deposition to pilchards. The transfer coefficient was calculated to be 1.85 x 10(-3) Bq yr kg-1/(Bq m-2). The dose incurred by pilchard consumption was estimated for the Croatian population, the annual collective equivalent dose being less than 0.1 Sv. PMID- 8192603 TI - Ferruginous bodies in the lungs of urban dogs. AB - The aim of the study was to assess health hazards induced by environmental exposure to asbestos using urban dogs as biological indicators. Samples of the lung tissue taken from 36 randomly chosen urban dogs were examined. In the group of dogs aged up to four years (n = 15) ferruginous bodies were identified in only two. In the dogs older than four years (n = 21) 17 were ferruginous body positive. According to Fisher's exact test the difference between the two groups was significant (P < 0.001). The presence of asbestos bodies in the lungs of dogs is considered to be evidence of serious contamination of urban areas with respirable mineral fibres. The more frequent presence of asbestos bodies in the lungs of the older dogs indicates long-term accumulation of mineral fibres exceeding 10 microns in length. Continuous environmental exposure of the city's population to respirable mineral fibres may therefore pose a health risk. PMID- 8192604 TI - Hydrocarbons and chlorinated hydrocarbons in the air in the greater Split area. AB - The content of hydrocarbons and chlorinated hydrocarbons was examined in samples of air from the greater Split area. Organic pollutants were accumulated from the air by adsorption on Polysorb-10 and desorption with hot water vapour. Gaseous and liquid phases were analysed by gas chromatography. Hydrocarbon concentrations were within permissible limits and their effects on human health were negligible. There were marked differences between pollutant concentrations in air samples taken from the industrial zone, crossroads in the city centre and "clean" zones. PMID- 8192605 TI - Can the occurrence of bronchial asthma in potroom workers be prevented? AB - Bronchial reactivity was evaluated in a group of 35 workers at preemployment examination using the metacholine test. Three workers showed an increased bronchial reactivity, the rate being in accordance with the previous experience. Ten randomly chosen subjects with normal reactivity, who were engaged as potroom workers, were followed up during a two-to-five-year period. None of them experienced any significant respiratory complaints and their bronchial reactivity also remained normal. Only one worker had a borderline finding (PD20FEV1). Although selection at preemployment medical examination is a measure that has to be used only exceptionally, based on the finding obtained by non-specific bronchoprovocation challenge it seems that it can be recommended in the case of that particular exposure. PMID- 8192606 TI - [Exposure to benzene and hematologic changes in workers at the Ina-Oki Drnisplast factory in Drnis]. AB - In the summer of 1984 workers in the "INA-OKI Drnisplast" factory frequently complained about headaches, weight loss and irregular menstrual cycles. According to the factory engineers that might have been due to an altered composition of the paints and glues that were used in the manufacturing process that year. Those had been found to lack specifications of chemical composition. Experts from the Institute for the Safety at Work from Zagreb were called in to perform measurements of organic solvents content in the workroom air. Benzene concentrations were found to be up to five times higher than the maximum permissible levels, those of toluene up to three times and of cyclohexane up to ten times higher. The polluted part of the factory was closed down, changes were introduced into the working process (use of paints was stopped, only glues without benzene content were allowed and proper ventilation was installed) and all the workers, twenty in all, received medical treatment. After three months the working process was resumed. In 1989 all the twenty workers underwent a control medical examination. All showed signs of recovery, both objective and subjective. Their blood tests values were within normal range. All the workers continued working, save one who retired in 1988 upon recommendation of a disability commission. The cause of disablement was occupational disease--benzene poisoning. On the basis of this experience emphasis is placed on the importance, in working with benzene, of complying with the Legislation on working capacity assessment for jobs requiring special working conditions and with the Safety at work act. PMID- 8192607 TI - International interlaboratory comparison of lead and cadmium determination in samples of suspended particulate matter. AB - Equal parts of six real samples of suspended particulate matter were analysed for lead and cadmium by laboratories in three different countries. The results agreed very well. The agreement is encouraging considering queries that arise when results in international projects are compared. PMID- 8192609 TI - [Criteria for recognizing asbestosis as an occupational disease]. AB - The commentary deals with the development of asbestos disease, its cause and latency, especially in connection with the carcinogenic effect of asbestos exposure. Diagnostic criteria and the approach to disability assessment are summarized. Legislative and organizational aspects in the assessment of the disease as occupational are discussed. PMID- 8192608 TI - Radioprotective agents in medicine. AB - The diminished probability of strategic nuclear confrontation alleviates some of the global concerns about large numbers of radiation casualties in the event of a nuclear war. As a result of the protection of the environment, the management of smaller numbers of radiation casualties assumes a more predictable and more specific role confined to accidents in nuclear energy projects, industry, technology and science. Recent experience of the consequences of accidents in nuclear power plants, in the field of radiotherapy and in the disposal of radioactive waste and spent fuel, present the medical and scientific communities with formidable problems if such events are to lead to minimal adverse effects on the biosphere. Whereas it is not possible to predict a nuclear or radiation accident, radioprotection is hardly an issue of health science alone, but rather an issue of the strictest quality assurance in all aspects of the utilization of nuclear energy and ionizing radiation. Thus, the medical community concerned with radioprotection will have to confine its emphasis on the management of radiation induced alterations of the human organism from acute radiation syndromes to the stochastic concepts of chronic alterations of radiosensitive organic systems. Current multidisciplinary research in the field of radioprotection involves all aspects of basic and clinical research ranging from the subatomic mechanisms of free radical formation, macromolecular and intracellular radiation-induced alterations, biochemical and physiological homeostatic mechanisms and organ level manifestations to the clinical management of radiation casualties in a controlled hospital environment. Radioprotective agents, although widely studied in the past four decades and including several thousand agents, have not reached the level of providing the field of medicine with an agent that conforms to all criteria of an optimal radioprotectant, including effectiveness, toxicity, availability, specificity and tolerance. This article discusses the current state of radioprotection in medical therapy, and emphasizes a need for continued research in the area of medical management of radiation casualties from the viewpoint of a realistic probability of nuclear incidents or accidents in the nuclear energy dependent world at the end of the millennium. PMID- 8192610 TI - Measuring the effect of the duration of problem drinking on cognitive functions in alcoholics. AB - Although research has been conducted to determine the effects of the duration of problem drinking on cognitive functioning, the findings are inconclusive. The duration of problem drinking does not seem to be in a linear relation to the cognitive functions of alcoholics. This study tested the hypothesis according to which the duration of problem drinking is connected with cognitive functioning only at the beginning of abstinence, when withdrawal symptoms are present and when the spontaneous recovery of cognitive functions has hardly started. Once the withdrawal symptoms have gone, between-subjects variation in spontaneous recovery probably hides the effect of the duration of problem drinking. A total of 179 Finnish male alcoholics took part in the study. Randomly assigned to three groups, the subjects were tested during the first, second or fourth week of abstinence. The hypothesis was supported by the data. PMID- 8192611 TI - [A case of Wernicke's encephalopathy which accompanied a passing blindness]. AB - The case of a chronic alcoholic patient with Wernicke's encephalopathy accompanied by passing blindness is reported and the alcoholic amblyopia is discussed in this study. The patient was a 39 year-old male who had been a heavy drinker for 13 years, and was habitually inebriated for the last one year. Disturbance of consciousness ataxia of gait, nystagmus and blindness were manifested on admission. Decreased level of serum vitamin B1 was also recognized at admission. The symptoms diminished from about a month after admission except for horizontal nystagmus. Since the patient had racket-like scotoma in his central visual field, his blindness was thought to be alcoholic amblyopia. Although alcohol dependence is associated with many physical disabilities, there are few reports about Wernicke's encephalopathy with alcoholic amblyopia. This case demonstrates the importance of careful physical examination for understanding alcohol-related disabilities and alcohol dependence. PMID- 8192613 TI - [A study on preventive measures for redrinking in alcoholics]. AB - We conducted a questionnaire survey on reasons or situations that lead alcoholics to start drinking alcohol, and measures to overcome the craving for alcohol. The subjects were 187 alcoholics (mean age; 53.9 +/- 9.9) who were outpatients of Kurihama National Hospital or the members of "Danshu-kai" (Japan Sobriety Association). Their mean abstinent period at the time of this survey was 43.6 months. To examine the relationship between various factors such as demographic backgrounds, reasons to start drinking, and measures to overcome craving and the length of abstinent periods, the subjects were divided into two groups in terms of abstinent periods; long-term group (24 months or more of abstinence, 88 cases) and short-term group (less than 24 months of abstinence, 99 cases). As reasons for taking the last drink, "psychological problems" showed the highest percentage (20.3%), followed by starting drink without any reason (17.7%). Measures used most frequently to overcome craving were "thinking about their own lives" (34.8%), "contacting self-help groups" (22.5%), and "thinking about self-help groups" (20.9%). Interestingly, non-alcoholic beverages were often used to overcome craving; coffee or tea and non-alcoholic soda were most frequently used in the long-term group, and coffee or tea and milk in the short-term group. The results of this study suggest that there is no particular situation or reason of significance that specifically induces the craving for alcohol in alcoholics. They took various measures to overcome craving. From the viewpoint of managing craving, this study reconfirmed the significant importance of self-help groups for sustaining long-term abstinence. PMID- 8192612 TI - [The "addiction trends" seen among the wives of alcoholics. Report 2]. AB - It has been known that wives of alcoholics tend to show an unhealthy relation with their husbands. The test called ASTWA (Addictions Screening Test for Wives of Alcoholics), which we developed earlier and reported in the previous paper in detail, might be useful for both wives and therapists for helpful suggestions. In this report, the present authors try to evaluate the ASTWA scores obtained from the wives, which consist of "a total score," "caring trends", "dominating trends," "obsessive traits," and "trends toward lowering of self-esteem," making clear each of the critical points between normal and abnormal sifting trends with the help of a normal control study. The results are demonstrated graphically as in the YG Test. In this way, the reliability, the validity, and the usefulness of ASTWA were confirmed in the process of this study. A prospective study concerning the prognosis of alcoholism of their husbands in relation to the results of ASTWA was carried out. In the non-intervened group, wives of the abstinence group tended to show a lower score than in those of the slipped group in terms of the total score, the dominating trends, the obsessive traits, and the trends toward lowering of self-esteem. In the group in which three months of initial therapy for wives have been completed, a significant parallel correlation was found between the ASTWA results and the prognosis of abstinence of their husbands. These results suggest that the total score, the caring trends, dominating trends, and the involved traits would indicate a degree of healthiness or unhealthiness in the marital relationship, particularly in terms of a circular cause and effect relation in developing alcoholism, and also would be a prospective indicator of the prognosis of alcoholism of their husbands. PMID- 8192614 TI - Cocaine abuse in Japan. AB - During the past several years, Japan has seen an emergence of cocaine abuse. Although there were only 43 cocaine-related arrests in 1988, the number in 1989 jumped to 96-more than double the previous year. In 1991, the number increased to 122. National Police Agency data shows that about 50% of methamphetamine (MAP) violators had been arrested for drug use. In comparison, only about 5% of cocaine arrests were for drug use, whereas about 50% were for possession, a pattern more similar to that of marijuana violators than MAP violators. More violators were in their 20's for cocaine and marijuana violations than for MAP violations. The percentage of foreigners involved was about 27% for cocaine and about 10% for marijuana, figures greater than the percentage for MAP (about 4%). The first cocaine patients to emerge were the two reported in a 1989 nationwide psychiatric hospital survey. This came two years after the first reporting of marijuana patients. In a similar 1991 survey, two more cocaine patients were reported. Three of the four cocaine patients had abused marijuana prior to abusing cocaine. Marijuana patients and MAP patients have the following demographic differences: about 57% of marijuana patients but only about 4% of MAP patients had enrolled in junior colleges, colleges or universities; and about 71% of marijuana patients but only about 5% of MAP patients were from high income families. Only about 14% of marijuana patients but about 74% of MAP patients had previously been apprehended. These patterns suggest that, demographically, cocaine abusers in Japan are more similar to marijuana abusers than MAP abusers. PMID- 8192615 TI - [The effect of flumazenil administration on acute cocaine intoxication of rats]. AB - Flumazenil was studied on cocaine intoxicated rats for its preventive effect on seizure, death and loss of righting reflex. Two minutes after the intraperitoneal injection of cocaine (70 mg/kg) into a rat, flumazenil and diazepam were administered at the clinically corresponding dose intraperitoneally. Flumazenil at a dose 0.125 mg/kg extended the onset time of the cocaine induced seizure. Flumazenil at 0.5 or 1.0 mg/kg with diazepam 2.0 mg/kg, prevented the seizure, and kept righting reflex. It was observed that use of flumazenil in combination with cocaine had the effect of the benzodiazepine receptor. PMID- 8192616 TI - A model of developmental change in hierarchical phenotypes with application to specific cognitive abilities. AB - A hierarchical longitudinal path model is described for analysis of twin and sibling data. The model combines multivariate and longitudinal methodologies for assessment of continuity and change in the relationships among characters over time. Additionally, the model permits assessment of shared and independent etiologies for groups of measures at single and multiple occasions. The procedure is illustrated by application to specific cognitive ability data from 103 adopted and 109 nonadopted sibling pairs at ages 3, 4, 7, and 9 years, and 50 pairs of monozygotic and dizygotic twins at ages 3 and 4 years. The results suggest that much of the observed continuity in general intelligence measures is attributable to genetic influences common to specific abilities and indicate differential etiologies for specific abilities at different occasions in childhood. PMID- 8192617 TI - Simultaneous genetic analysis of means and covariance structure: Pearson-Lawley selection rules. AB - The object of this paper is to indicate that the Pearson-Lawley selection rules form a plausible general theory for the simultaneous genetic analysis of means and covariance structure. Models are presented based on phenotypic selection and latent selection. Previously presented quantitative genetic models to decompose means and covariance structure simultaneously are reconsidered as instances of latent selection. The selection rules are very useful in the context of behavior genetic modeling because they lead to testable models and a conceptual framework for explaining variation between and within groups by the same genetic and environmental factors. PMID- 8192618 TI - Genetic and environmental influences on early childhood behavior. AB - The Child Behavior Checklist for Ages 2-3 (Adelbach et al., J. Abnorm. Child Psychol. 15;629-650; 1987) was completed by mothers of 229 pairs of twins (mean age = 33 months). Using the two broad-band groupings of Internalizing and Externalizing described by Achenbach et al. (1987), various models to estimate genetic and environmental parameters were fitted using LISREL 7. Model-fitting results showed that the genetic components to the observed phenotypical variation were small and not necessary in the model. Influences from the shared environment, however, could not be dropped from the model without a deterioration in fit. Parameter estimates were not significantly different in boys and girls. PMID- 8192619 TI - A model system for analysis of family resemblance in extended kinships of twins. AB - The "Virginia 30,000" comprise 29,698 subjects from the extended kinships of 5670 twin pairs. Over 80 unique correlations between relatives can be derived from these kinships, comprised of monozygotic (MZ) and dizygotic (DZ) twins and their spouses, parents, siblings, and children. This paper describes the first application of a fairly general model for family resemblance to data from the Virginia 30,000. The model assesses the contributions of additive and dominant genetic effects in the presence of vertical cultural inheritance, phenotypic assortative mating, shared twin and sibling environments, and within-family environment. The genetic and environmental effects can be dependent on sex. Assortment and cultural inheritance may be based either on the phenotype as measured or on a latent trait of which the measured phenotype is an unreliable index. The model was applied to church attendance data from this study. The results show that the contributions of genes, vertical cultural inheritance, and genotype-environment covariance are all important, but their contributions are significantly heterogeneous over sexes. Phenotypic assortative mating has a major impact on family resemblance in church attendance. PMID- 8192620 TI - Handedness as a continuous variable with dextral shift: sex, generation, and family handedness in subgroups of left- and right-handers. AB - Percentages of left-handed relatives were compared between subgroups of left handers and of right-handers to test the prediction that the subgroups are ordered for probability of carrying the rs +/gene (hypothesized by the right shift theory of handedness). Data included families of undergraduates and Open University students who described their children as well as other relatives. Linear relationships were found between subgroup order and percentage of left handed relatives. In agreement with previous evidence that some right-writers with weak sinistral preferences (class 2) are in fact more dextral than consistent right-handers (class 1), class 2 tended to have fewer left-handed relatives than class 1 in both samples. Left writers with weak dextral tendencies (class 7) tended to have more left-handed relatives that consistent left-handers (class 8). Comparisons of the distribution of subgroup handedness in undergraduates and their parents revealed strong effects for sex and for generation. In both cases, the main contrasts were not between left-handers and right-handers but between left-handers plus right-handers with weak dextrality and right-handers with strong dextrality. The findings are consistent with the theory that the relevant factor is not handedness as such but, rather, the absence or presence of the rs +/gene. PMID- 8192621 TI - Replication of asymmetry of a-b ridge count and behavioral discordance in monozygotic twins. AB - We have replicated an earlier study (Rose et al., Behav. Genet. 17, 125-140, 1987) relating dermatoglyphic asymmetry to intrapair discordance in a completely new sample of monozygotic (MZ) twins. Consistent results were observed for at least 31 of 37 Minnesota Multiphasic Personality Inventory (MMPI) scales tested in the two samples. Intrapair differences were confirmed to be greater in 28 MZ pairs with asymmetric palmar a-b ridge counts than in 29 MZ pairs with little or no a-b asymmetry for at least 15 scales. We also examined longitudinal stability over a 4 to 5-year period for six MMPI scales and found suggestive evidence in three scales for greater test-retest instability in twin pairs asymmetric for a-b ridge count. The results offer new evidence for our hypothesis that an asymmetric a-b ridge count may identify individuals who are poorly buffered from developmental noise, but analyses of symmetric and asymmetric a-b ridge counts in nontwin subjects are required to extend and test the hypothesis further. PMID- 8192622 TI - Studies on wild house mice. V. Aggression in lines selected for attack latency and their Y-chromosomal congenics. AB - Congenic lines were made for the Y chromosome between aggressive and nonaggressive lines of house mice, which were previously established by artificial selection in wild mice for short attack latencies (SAL line) and long attack latencies (LAL line). The aggressiveness of the males in successive backcross generations of the congenic lines is reported. Results fit the hypothesis that the Y-chromosomal effect that is often found for aggression in house mice may be located on the pseudo-autosomal region of this chromosome. PMID- 8192623 TI - Differences in response to an acoustic startle stimulus among forty-six rat strains. AB - The startle response to intense environmental stimuli is found in most, if not all, animal species. Previous studies have shown that selected rodent strains differ in startle response to an acoustic stimulus, suggesting genetic variability. The current experiment was designed to extend these differences to a wider range of rat strains. Forty-six inbred and outbred rat strains were studied. These strains exhibited differences in both the mean amplitude of the startle response and the rate of habituation to startle stimuli over repeated trials. In addition, there was a significant relationship between these measures. These results suggest that robust phenotypic differences in startle response exist among rat strains. As previous investigations have demonstrated a direct relationship between the startle response and other behavioral end points, the use of strain differences in startle response may be an effective way to determine genetic contributions to specific behavioral responses. PMID- 8192624 TI - Secondary courtship songs and inhibitory songs of Drosophila virilis-group males. AB - The males of all Drosophila virilis-group species produce primary courtship song; and the males of four of these species also provide secondary courtship song when courting a female. The amount of secondary song and the courtship phase at which it is produced vary according to the species. D. lummei males produce secondary song consisting of successive 12-ms-long sound pulses with 70-ms-long intervals between pulses. D. borealis males produce short and dense pulse trains and D. littoralis and D. flavomontana males produce single sound pulses of a long duration (80-160 ms). The males of all species produce pulse-structured inhibitory song when they are courted by another male. In the secondary and inhibitory songs of interspecific hybrids, short and dense pulse trains of parent species break into pulse song with long interpulse intervals. This suggests that songs consisting of short and dense pulse trains and pulse songs with long interpulse intervals are just different modes of the same song. Sine songs (long sound pulses) seem to be inherited independently of pulse song. PMID- 8192625 TI - Male polymorphism in Limia perugiae (Pisces: Poeciliidae). AB - The male-polymorphic poeciliid fish, Limia perugiae, a small teleostean endemic to the southeast of the Caribbean island Hispanola, consists of three male size morphs with uniform females. Large males differentiate at a size varying between 25 and 38 mm; intermediate males, between 21 and 25 mm. Under competition, large males exhibit an elaborate courtship display, whereas small males show only a sneak-chase behavior. Intermediate males adapt their tactics to the respective competitors. However, all male morphs can switch from courtship display to sneak chase behavior. In large mating groups with four males of different size and five or six virgin females, large dominant alpha-males as well as small subordinate delta-males did not produce any offspring. Unexpectedly, all progeny were sired exclusively by the intermediate subordinate beta- and gamma-males. Breeding experiments with the three male morphs can best be explained by a model of Y linked genes for small and large size which are both suspended by the activity of an autosomal recessive repressor responsible for the development of intermediate males. The dominant allele of the recessive repressor, in either its homoorits heterozygous state, activates the Y-chromosomal genes for large or small size, respectively. Accordingly, intermediate males may produce male offspring of all size classes, depending on the presence of either the Y-linked gene or the autosomal repressor. PMID- 8192626 TI - Psychological morbidity associated with motor vehicle accidents. AB - Fifty victims of recent motor vehicle accidents (MVAs), who had sought medical attention after their accidents, were assessed for possible psychological morbidity as a result of the accident. Forty age, gender-matched controls were also assessed with the same instruments. Forty-six percent of the MVA victims met the criteria for current post-traumatic stress disorders (PTSD) as a result of the accident while 20% showed a sub-syndromal version (the reexperiencing symptom cluster plus either the avoidance/numbing cluster or the over-arousal cluster) of PTSD. Although all MVA victims showed some form of driving reluctance, only 1 S met the criteria for driving phobia. Those MVA victims who met the criteria for PTSD or sub-syndromal PTSD were significantly more likely to have experienced previous trauma, other than a serious MVA, and were more likely (P = 0.008) to have previously met the criteria for PTSD as a result of that trauma. Forty-eight percent of MVA victims who met the criteria for current PTSD also met the criteria for current major depression. Significantly more current MVA-PTSDs had suffered previous major depressive episodes. PMID- 8192627 TI - Is evaluative conditioning a qualitatively distinct form of classical conditioning? AB - This paper contains a critical review of the claim that evaluative conditioning (EC) represents a theoretically distinct form of classical conditioning. A review of the evidence suggests that: (i) while it is claimed that EC can occur without awareness, EC studies have either adopted inappropriate statistical comparisons to demonstrate this or have failed to use the control conditions necessary to indicate that what is being measured is associative conditioning; (ii) there is no theoretical reason why conditioning without awareness might be observed in any conditioning paradigm if a relatively complex covariation assessment procedure such as that adopted in EC studies is used; and (iii) there are a variety of possible explanations for the relative resistance to extinction reported with EC, some of which allude to failure to use appropriate control conditions and others which point to specific details unique to the EC extinction procedure. Until these appropriate procedural and statistical comparisons are made, it is concluded that it is premature to assume that EC represents a form of conditioning that is theoretically distinct from other types of classical conditioning. PMID- 8192628 TI - The evaluative response: primitive but necessary. AB - We do not believe the claim that "evaluative conditioning is a qualitatively distinct form of classical conditioning" [Davey (1994). Behaviour Research and Therapy, 32, 291-299]. We view all classical conditioning as a learning process which leads organisms to assign a positive or negative value to previously neutral stimuli and to respond to them accordingly. The evaluative response is a necessary component of this process and hence it is central to all classical conditioning, not a separate type. Davey concentrates on a signal-based information processing view of learning, i.e. the formation of linear associations between CS and UCS of which human subjects are aware and which they can verbalize. We propose a more primitive and more general model in which stimulus evaluation (like/dislike) occurs with a minimal degree of processing, and enters into a representation of stimulus (CS and UCS) and response (CR and UCR) characteristics which is reintegrative rather than associative. PMID- 8192629 TI - Pollution of the mind. PMID- 8192630 TI - The emotional Stroop interference effect in anxiety: attentional bias or cognitive avoidance? AB - Interference effects on threat words in anxious subjects on the emotional Stroop task have generally been interpreted as evidence for mood-congruent attentional bias in anxiety states. However, several recent studies have yielded results that run contrary to this attentional bias explanation. The most important of these conflicting findings show that: (1) panic disorder patients displayed interference on threat words, but also on other emotional words, including positively valenced words, and (2) 'repressors' showed even greater interference than high trait anxious subjects. We propose an alternative explanation for these findings, in which both attentional bias and cognitive avoidance are assumed to operate in the emotional Stroop task, but in which cognitive avoidance is hypothesized to be chiefly responsible for the greater interference effects found in anxious subjects and 'repressors'. We suggest that future research into cognitive processes associated with anxiety states should employ a variety of experimental paradigms on the same subjects and include measures of 'defensiveness'. PMID- 8192631 TI - Maternal depressive mood: the role of the father in preventing adolescent problem behaviors. AB - The current study examines the role of the father-adolescent relationship as a buffer for maternal depressive mood in a nonclinic young adolescent sample (n = 282). Internalizing and externalizing problems, as well as grade point average, were examined. Results indicated that, for all three variables, maternal depressive mood was associated with poorer functioning. Of most importance, for internalizing and externalizing problems, a good father-adolescent relationship served to buffer the adolescent from maternal depressed mood. This effect existed regardless of the gender of the adolescent or parental marital status. The findings suggest that behavior problems are associated with even mild levels of one family stressor, maternal depressive mood, and that these problems can be counteracted through an intrafamilial support system--the father. Implications for the behavior therapist are considered. PMID- 8192632 TI - Worrying, social problem-solving abilities, and social problem-solving confidence. AB - This study investigated the relationship between worrying and two features of social problem solving: problem-solving ability and confidence. However, while levels of worrying were significantly related to both poor problem-solving confidence and poor perceived control over the problem-solving process, worrying was unrelated to problem-solving ability per se. The failure to find a relationship between worrying and social problem-solving skills was found separately at both low and high levels of worrying, and also when levels of trait anxiety had been controlled for. These results provide no support for the hypothesis that chronic worrying results from poor social problem-solving abilities, but the results are consistent with the belief that worrying is primarily an anxiety-related phenomenon with any problem-solving deficits occurring at the level of solution implementation rather than solution generation. PMID- 8192633 TI - The self, attributional processes and abnormal beliefs: towards a model of persecutory delusions. AB - In this paper we review a series of recent investigations into cognitive abnormalities associated with persecutory delusions. Studies indicate that persecutory delusions are associated with abnormal attention to threat-related stimuli, an explanatory bias towards attributing negative outcomes to external causes and biases in information processing relating to the self-concept. We propose an integrative model to account for these findings in which it is hypothesized that, in deluded patients, activation of self/ideal discrepancies by threat-related information triggers defensive explanatory biases, which have the function of reducing the self/ideal discrepancies but result in persecutory ideation. We conclude by discussing the implications of this model for the cognitive-behavioural treatment of paranoid delusions. PMID- 8192634 TI - Obsessions, overvalued ideas, and delusions in obsessive-compulsive disorder. AB - The prevailing view is that individuals with obsessive-compulsive disorder (OCD) are able to think rationally about their obsessive concerns and are thus able to recognize them as senseless. However, clinical observations indicate that at least some obsessive-compulsives do not regard their symptoms as unreasonable or excessive, and their ideas have been characterized as overvalued or delusional. In the present paper the concepts of obsessions, overvalued ideas, and delusions are discussed and compared, and the available studies of insight among obsessive compulsives are reviewed. It is concluded that obsessive-compulsive ideas can not satisfactorily be dichotomized according to patients' insight, and that the notion of a continuum of strength of obsessive-compulsive beliefs is more appropriate. The relationship between degree of obsessive-compulsive conviction and outcome of therapy remains unclear. Methodological issues that complicate our understanding of OCD are considered, and theories of delusions are examined in relation to their development in OCD. PMID- 8192635 TI - A cognitive approach to measuring and modifying delusions. AB - The present paper summarizes and integrates with the existing literature the results of three studies we have conducted on the measurement and modification of delusions. The findings of two of these studies have been presented previously; the third is briefly reported here. A total of 12 people with delusions took part. Ten participated in two investigations that used between-subject multiple baseline designs; the remaining two, each of whom held three distinct delusions, took part in a study using an across-beliefs multiple-baseline design. A variety of dimensions of delusional experience were monitored over baseline periods of at least 4 weeks, and two distinct cognitive interventions were used: a structured verbal challenge and a planned empirical test. Our focus in the present article is on intervention and the process of change as people come to question and sometimes reject their delusions. We also address related issues, including problems of measurement (i.e. demand characteristics, independent validation), the connection between depression and delusions and the prediction of treatment response. We conclude with specific recommendations for cognitive therapy for delusions. PMID- 8192636 TI - Cognitive therapy of delusional beliefs. AB - The present article articulates a cognitive theoretical perspective of delusional beliefs. In contrast to the focus of psychoanalytic therapy (theoretically derived phenomena beyond personal awareness), the cognitive therapist focuses primarily on the conscious cognitive-experiential level in the treatment of delusional beliefs, thereby emphasizing a 'common-sense' level of analysis or reasoning shared by the delusional patient. Unlike noncognitive behavioral approaches, which focus on topographical 'verbal behavior' as such, cognitive therapy directly targets specific delusional beliefs which theoretically give rise to the disordered verbal behavior. In this article, the adaptation of cognitive therapy to the treatment of delusions is described, with special attention to the following issues: special problems in collaboration; difficulties in obtaining conviction ratings; how to avoid and reduce confrontation through the Socratic method; the collaborative design of homework experiments; distancing strategies; interpersonal relationship issues; and the necessity to identify and explore the emotions associated with the various delusions, especially feelings about the possibility that the delusions may be incorrect. PMID- 8192637 TI - A multicomponent behavioral treatment for social phobia: social effectiveness therapy. AB - The development of a new, comprehensive and multicomponent treatment for social phobia is described. Initial results of a pilot study with the new treatment also are reported. The treatment was found to be effective with severe (generalized) social phobics, most of whom had co-occurring Axis I and/or II conditions. In addition to significant change on a host of outcome variables, a normative-based endstate functioning index was used to determine treatment efficacy. The results are discussed with respect to the implementation of the treatment and in terms of the need for a comprehensive approach to treating social phobia. PMID- 8192638 TI - Two dimensional views of psychopathology. AB - Two dimensional views of adult psychopathology are discussed: (a) the phenomenological view according to which symptoms of psychopathology can occur in normal people in less intense, persistent and debilitating, but not qualitatively different forms; and (b) the vulnerability view according to which the degree to which a person possesses the apparent normal counterparts of the symptoms of a psychopathological disorder is an index of that person's vulnerability for the disorder. Examples of research using questionnaires designed by two prominent advocates of these dimensional views, namely, H. J. Eysenck and L. J. Chapman, are reviewed. It is concluded that the research strategies to date do not provide adequate tests of the phenomenological view and provide only weak support for the vulnerability view. Alternative, more direct, research strategies are proposed. PMID- 8192639 TI - Obsessive intrusive thoughts in nonclinical subjects. Part II. Cognitive appraisal, emotional response and thought control strategies. AB - This second part of the study reports on the appraisal and thought control responses of 270 students to their most upsetting intrusive thought. Multiple regression analysis revealed that belief that one could act on the intrusive thought and perceived uncontrollability of the thought were the two most important predictors of the frequency, or persistence of the distressing intrusion. Intrusions rated as very difficult to control were also associated with increased belief that one could act on the intrusion, avoidance of situations that may trigger the intrusion, reduced success with one's most typical thought control strategy and higher thought frequency. Based on the Padua Inventory Total score, high and low obsessional Ss were selected. Highly obsessional individuals reported more unwanted obsessive intrusive thoughts and rated their thoughts as significantly more frequent and believable than low obsessive individuals. The type of thought control strategy typically used was not a factor in thought frequency and controllability, nor did it differentiate between high and low obsessional groups. The results are discussed in terms of Salkovskis' cognitive model of obsessions and intrusive thoughts. PMID- 8192640 TI - Anxiety sensitivity and panic attacks in an asthmatic population. AB - The purpose of this study was to examine the relationship among anxiety sensitivity, the experience of frequent, spontaneous panic attacks, and pulmonary function in individuals with asthma. Ninety-three asthmatics participated by completing a battery of questionnaires and a spirometric assessment. Twenty-three percent of the asthmatics reported a history of spontaneous panic attacks with 9.7% reporting attacks that were severe and frequent enough to meet the DSM-IIIR criteria for panic disorder (PD). Anxiety sensitivity (ASI) scores, but not pulmonary function, was significantly related to PD. In addition, we compared the asthmatics (with and without PD) to 10 clinically diagnosed PD Ss without asthma and to 32 nonanxious, nonasthmatic controls on the ASI, the Body Sensations Questionnaire, and the Agoraphobic Cognitions Questionnaire. Whereas Ss with PD (asthmatic and nonasthmatic) displayed significant elevations on these measures compared to those without PD, the presence of asthma alone had no effect. The present study concurs with that of Porzelius et al. [Behaviour Research and Therapy, 30, 75-77 (1992)] in extending the validity of the cognitive model of PD to individuals with pulmonary disease. PMID- 8192641 TI - Treatment of borderline personality disorder: a challenge for cognitive behavioural therapy. AB - Patients with so-called Borderline Personality Disorder are generally considered as extremely difficult to treat. Until recently, conceptualizations of this severe disorder on which cognitive-behavioural therapy could be based were underdeveloped. The present paper presents a cognitive formulation based on previous cognitive and behavioural conceptualizations, and on empirical evidence pertaining to the relationship between childhood traumas and Borderline Personality Disorder. It is assumed that chronic traumatic abuse or neglect in childhood has led to the development of almost unshakeable fundamental assumptions about others (dangerous and malignant), about one's own capabilities (powerless and vulnerable) and upon one's value as a person (bad and unacceptable). These are assumed to underlie the complex symptomatic presentation of borderline patients. A treatment protocol is described, which takes 1.5-4 years, and consists of 5 stages: (1) construction of a working relationship; (2) symptom-management (gaining more control over symptoms); (3) correction of thinking errors; (4) emotional processing and cognitive re-evaluation of the childhood trauma and schema changes; and (5) termination. A case example is presented, and a call for research into the efficacy of this approach is made. PMID- 8192642 TI - The abstinence violation effect in child molesters. AB - The reformulation of the abstinence violation effect (AVE) is briefly described together with the empirical support for the construct. Twenty-six incarcerated male child molesters were assessed, using the Differential Emotions Scale and the Attributional Dimension Scale, at three points (high-risk, lapse, and relapse) while they listened to an audiotaped recording of a description of their most typical offense chain. Eighteen Ss experienced an AVE at the point of relapse and 7 as a result of lapse. There were significant increases in most negative emotions and decreases in interest over the relapse chain. There were significantly higher disgust, contempt, hostility, fear, shame, shyness and anger scores reported by those showing an AVE. Conversely, the AVE group showed significantly lower scores for joy and surprise. There were no significant differences on any of the 4 attributional dimensions across the relapse process but those showing an AVE reported significantly more uncontrollability and higher stability scores. The significance of these results for clinical practice are discussed. PMID- 8192643 TI - Induced mood, phobic responding and the return of fear. AB - The link between depression and phobic responding is poorly understood. Forty eight spider phobics were exposed to videotaped spider sequences whilst in relatively depressed or relatively elated moods, then presented the same stimuli whilst in a neutral mood. Results indicated that depressed mood increased initial responding, and was associated with greater return of fear during the second (non mood) sequence. The return of fear was not attributable solely to differential habituation rates during the first sequence, suggesting that the differences observed may have been due to cognitive effects. PMID- 8192644 TI - Infrequent panic: physiological and subjective reactions to hyperventilation. AB - Forty-eight females were evaluated to detect differences in panic-related symptomatology and physiological responses to 2 min of hyperventilation. Ss were divided into 3 groups: infrequent panickers; no panic/high trait anxiety; and no panic/low trait anxiety. The low trait anxiety group scored significantly lower on various self-report measures of anxiety-related symptomatology compared to Ss with infrequent panic and high trait anxiety. Hyperventilation produced no significant group differences in physiological reactivity or recovery. However, Ss with low trait anxiety reported significantly less severe sensations and a significantly lower incidence of panic during hyperventilation than the infrequent panickers and the high trait anxiety group. Ss who panicked during hyperventilation reported more intense sensations and negative cognitions than those who did not panic. Thus, Ss were distinguished by their subjective, but not their physiological responses. PMID- 8192645 TI - Global social skill ratings: measures of social behavior or physical attractiveness? AB - Calvert reviewed the literature on social skills and physical attractiveness and concluded that many ratings of social skill may be confounded by the physical attractiveness of the target individual, possibly due to a general perception that physical attractiveness and social competence are positively correlated. In order to examine the influence of physical attractiveness on social skill ratings, Ss made global ratings of social skill and attractiveness for a confederate whose appearance and behavior had been altered to appear attractive or unattractive and socially skilled or unskilled in an assertiveness and heterosocial vignette. The results indicated that the same skilled behavior was viewed as more competent when performed by an attractive person compared to an unattractive person. Attractiveness had no influence on ratings of generally incompetent behavior. Thus, it appears that physical attractiveness does not compensate for poor interpersonal skills, but a skilled, attractive individual may be judged to have particularly good skills. Implications for the assessment of social skills are discussed. PMID- 8192646 TI - A composite measure to determine improvement following treatment for social phobia: the Index of Social Phobia Improvement. AB - This article describes the development of a composite index to determine improvement in treatment outcome research with social phobia. The index is comprised of 5 individual outcome measures that tap various domains of social phobia and assess the disorder via multiple methods (e.g. self-report, clinical ratings, behavioral performance). The ability of the index to determine improvement over treatment, and its initial concurrent validity are discussed. PMID- 8192647 TI - Suppression of Gi alpha 2 enhances phospholipase C signalling. AB - G-proteins mediate transmembrane signalling from a populous group of cell-surface receptors to a smaller group of effectors that includes adenylate cyclase, various ion channels and phospholipase C. Stem cells (F9 teratocarcinoma) or rat osteosarcoma 17/2.8 cells in which Gi alpha 2 expression is abolished by antisense RNA display markedly elevated basal inositol 1,4,5-trisphosphate accumulation and a potentiated phospholipase C response to stimulatory hormones. Expression of the Q205L mutant of Gi alpha 2, which is constitutively active, was found to block persistently hormonally stimulated phospholipase C activity, implicating Gi alpha 2 as an inhibitory regulator of phospholipase C signalling. Analysis using Gi alpha 2-deficient adipocytes of transgenic mice provided further evidence for a role for Gi alpha 2 in phospholipase C regulation, demonstrating in vivo that loss of Gi alpha 2 elevates basal, and markedly potentiates hormonally stimulated, phospholipase C activity. This report demonstrates for the first time that a single G-protein, G12, can regulate two distinct signalling pathways, i.e. adenylate cyclase and phospholipase C. PMID- 8192648 TI - Sphinganine 1-phosphate metabolism in cultured skin fibroblasts: evidence for the existence of a sphingosine phosphatase. AB - On addition of [4,5-3H]sphinganine 1-phosphate to human fibroblast monolayers, the label was efficiently removed from the culture medium. In contrast with the reported stability of phosphorylated sphingenine in 3T3 cells [Desai, Zhang, Olivera, Mattie and Spiegel (1992). J. Biol. Chem. 267, 23122-23128] and B16 melanoma cells [Sadahira, Ruan, Hakomuri and Igarashi (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 9686-9690], sphinganine 1-phosphate appeared to be subjected to a fast and extensive metabolism in fibroblasts, the major pathways being cleavage and dephosphorylation. The first of these pathways, catalysed by sphingosine phosphate lyase, resulted in the formation of labelled palmitaldehyde, which was recovered, mainly after oxidation, in glycerophospholipids in an ester bond. A smaller part of the palmitaldehyde was reduced and incorporated in alk(en)ylphospholipids. Dephosphorylation of spinganine 1-phosphate, a hitherto overlooked pathway catalysed by an unknown phosphatase(s), gave rise to sphinganine, which was converted by N-acylation into ceramide and then incorporated in spingomyelin and glycosphingolipids. PMID- 8192650 TI - Topoisomerase I action on the heterochromatic DNA from the brine shrimp Artemia franciscana: studies in vivo and in vitro. AB - The genomes of higher eukaryotes contain various amounts of tandem repeated DNA sequences (satellite DNA) typically located in the constitutive heterochromatin, the most highly condensed region of interphase chromosomes. We have previously demonstrated that an AluI DNA family of repeats is the major component of constitutive heterochromatin in the brine shrimp Artemia franciscana. The analysis of cloned heterochromatic fragments revealed that this repetitive DNA shows a stable curvature conferring a solenoidal geometry to the double helix. In this paper we provide evidence, using the antitumour drug camptothecin, that, in vivo, topoisomerase I cleaves heterochromatin with a frequency comparable with that observed in the whole genome. The analysis of the break sites shows that the enzyme cleaves heterochromatic DNA at specific sites characterized by a degenerate consensus sequence. Moreover the enzyme-mediated breaks have, in vitro, a degenerate consensus sequence similar to, but not identical with, the in vivo one. Some of these sites are influenced by the DNA flanking the heterochromatic insert, suggesting that structural variations could modify the enzyme specificity. PMID- 8192649 TI - Collagen type IV stimulates an increase in intracellular Ca2+ in pancreatic acinar cells via activation of phospholipase C. AB - Intracellular Ca2+ responses to extracellular matrix molecules were studied in suspensions of pancreatic acinar cells loaded with Fura-2. Collagen type I, laminin, fibrinogen and fibronectin were unable to raise cytosolic free Ca2+ concentration ([Ca2+]i), whereas collagen type IV, at concentrations from 5 to 50 micrograms/ml, significantly increased it. The effect of collagen type IV was not due to possible contamination with type-I transforming growth factor beta or plasminogen, as neither of these agents was able to increase [Ca2+]i. Using highly specific mass assays, concentrations of inositol lipids, 1,2 diacylglycerol (DAG) and Ins(1,4,5) P3 were measured in pancreatic acinar cells stimulated with collagen type IV. A decrease in the concentrations of PtdIns(4,5) P2 and PtdIns4 P with a concomitant increase in the concentrations of DAG and InsP3 mass were observed, showing that collagen type IV increases [Ca2+]i by activation of phospholipase C. The observed [Ca2+]i signals had two components, the first resulting from Ca2+ release from the intracellular stores, and the second resulting from Ca2+ flux from the extracellular medium through the verapamil-insensitive channels. A tyrosine kinase inhibitor (tyrphostine) was able to block inositol lipid signalling caused by collagen type IV, which together with the insensitivity of this pathway to cholera toxin and pertussis toxin or to preactivation of protein kinase C, the longer duration of the increase in [Ca2+]i and a longer lag period needed for observation of increases in DAG and InsP3 concentration with collagen type IV than with carbachol (50 mM) suggest that activation of phospholipase C by collagen type IV is caused by tyrosine kinase activation. Inositol lipid signalling and increases in [Ca2+]i were also observed with Arg-Gly-Asp (RGD)-containing peptide but not with Arg-Asp Gly (RDG)-containing peptide. Collagen type IV and RGD-containing peptide, but not carbachol, competed in increasing [Ca2+]i and DAG concentration, suggesting that the binding site of collagen type IV responsible for phospholipase C activation contains the RGD sequence. Together the present results suggest that, in pancreatic acinar cells, RGD sequence(s) within collagen type IV molecules cause activation of tyrosine kinase, probably through one of the integrin receptors, which then stimulates phospholipase C and increases [Ca2+]i. PMID- 8192651 TI - Micromolar calcium decreases affinity of inositol trisphosphate receptor in vascular smooth muscle. AB - The mechanism by which Ca2+ inhibits InsP3-induced Ca2+ release from sarcoplasmic reticulum of vascular smooth muscle was investigated. InsP3 binding to sarcoplasmic-reticulum vesicles from dog aortic smooth muscle was inhibited by 51 +/- 6% by 2 microM Ca2+ in the presence of 10 nM [3H]InsP3. Scatchard analysis indicated the presence of two InsP3-binding sites in the absence of Ca2+ (Kd = 2.5 +/- 0.9 and 49 +/- 8 nM InsP3), though the low-affinity site was more prevalent (representing 92 +/- 3% of the total number of binding sites). Ca2+ (2 microM) did not alter InsP3 binding to the high-affinity site (P > 0.05), but increased the Kd of the low-affinity site 3-fold (Kd = 155 +/- 4 nM InsP3; P < 0.001). The possibility that the apparent decrease in InsP3 affinity was caused by Ca(2+)-dependent activation of an endogenous phospholipase C could be excluded, because the Ca(2+)-dependent inhibition of InsP3 binding was completely reversible and insensitive to an inhibitor of phospholipase C. Moreover, Ca2+ did not inhibit InsP3 binding to InsP3 receptor partially purified by heparin Sepharose chromatography, though another fraction (devoid of InsP3 receptor) restored Ca(2+)-sensitivity of the partially purified InsP3 receptor. Thus Ca2+ binding to a Ca(2+)-sensitizing factor associated with the InsP3 receptor decreases the affinity of the receptor complex for InsP3. This Ca(2+)-sensitizing factor may provide a negative-feedback mechanism for regulating the rise in cytosolic Ca2+ concentration in vascular smooth muscle after hormone activation of the phosphoinositide cascade. PMID- 8192652 TI - Threonine synthesis from homoserine as a selectable marker in mammalian cells. AB - The plasmid pSVthrBC expresses the Escherichia coli thrB (homoserine kinase) and thrC (threonine synthase) genes in mouse cells and enables them to synthesize threonine from homoserine. After transfection with pSVthrBC and culture in medium containing homoserine, only cells that have incorporated pSVthrBC survive. Homoserine at concentrations greater than 1 mM is toxic to mammalian cells. Mouse cells selected from medium containing 5 mM homoserine had incorporated 20-100 copies of the plasmid per cell and had homoserine kinase activities of 0.001 0.012 nmol/min per mg of protein per copy. Cells selected from medium containing 10 mM homoserine had incorporated one or two copies of the plasmid per cell and had homoserine kinase activities of 0.06-0.39 nmol/min per mg of protein per copy. By using high concentrations of homoserine, it is possible to use pSVthrBC to select and isolate cell lines that have one or two copies of the plasmid incorporated into an active region of chromatin. CHO and HeLa cells have also been successfully transfected with pSVthrBC. COS-7 cells are naturally resistant to homoserine as they are able to metabolize homoserine. PMID- 8192653 TI - Identification and properties of a peptidyl dipeptidase in the housefly, Musca domestica, that resembles mammalian angiotensin-converting enzyme. AB - [D-Ala2,Leu5]Enkephalin was readily metabolized by membranes (40,000 g pellet) prepared from heads of the housefly, Musca domestica, with Gly3-Phe4 being the major site of cleavage. This hydrolysis was only partially inhibited (40%) by 10 microM phosphoramidon, an inhibitor of endopeptidase-24.11, but was almost totally abolished in the presence of a mixture of 10 microM phosphoramidon and 10 microM captopril, a potent inhibitor of mammalian angiotensin-converting enzyme (ACE). An assay for ACE employing Bz-Gly-His-Leu as the substrate was used to confirm the presence of an ACE-like peptidyl dipeptidase activity in fly head membranes. The peptidase had a Km of 1.91 mM for Bz-Gly-His-Leu and a pH optimum of 8.2. The activity was inhibited by 100 microM EDTA and was greatly activated by ZnCl2 but not other bivalent metal ions. Captopril, lisinopril, fosinoprilat and enalaprilat, all selective inhibitors of mammalian ACE, were also good inhibitors of the insect enzyme with IC50 values of 400 nM, 130 nM, 16 nM and 290 nM respectively. An M(r) value of around 87,000 was obtained for this enzyme from gel-filtration chromatography, indicating that the insect enzyme is similar in size to mammalian testicular ACE (M(r) = 90,000-110,000) and not the larger form of the enzyme (M(r) = 150,000-180,000) found in mammalian somatic tissues. The fly peptidyl dipeptidase was released from membranes into a soluble fraction by incubating the head membranes at 37 degrees C but not at 0 degree C, suggesting that the insect ACE-like enzyme can be solubilized from cell surfaces through the activity of a membrane-bound enzyme activity. In conclusion, we have shown the existence of a peptidyl dipeptidase in membranes from the heads of M. domestica, which has similar properties to those of mammalian ACE. PMID- 8192654 TI - Characterization of the antigens recognized by two monoclonal antibodies reactive with basal-layer keratinocytes of human epidermis. AB - Two monoclonal antibodies, GR3 and GR4, reactive with the basal-layer keratinocytes of human epidermis, were derived by immunization of Balb/c mice with glycoproteins isolated from cultured keratinocytes by lectin-affinity chromatography. Immunoprecipitation of Triton X-100 extracts from human keratinocytes metabolically labelled with D-[1-14C]glucosamine revealed that GR3 recognized a major glycoprotein with migration properties identical with those of a glycoprotein (reduced form M(r) 126,000) which was previously shown to be implicated in intercellular adhesion [Roberts and Brunt (1985) Biochem J. 232, 67 70]. In their unreduced forms the antigens recognized by GR3 and GR4 both migrated as two bands with M(r) values of 118,000 and 147,000. Comparison of 125I labelled glycoproteins immunoprecipitated by GR3, GR4 and integrin antibodies revealed that, under reducing conditions, the major band immunoprecipitated by both GR3 and GR4 co-migrated with the alpha 3 and beta 1 integrin chains. In addition the immunoprecipitate obtained with GR4 contained an additional band co migrating with the alpha 2 integrin chain. Sequential immunoprecipitation studies with GR3, GR4 and integrin antibodies confirmed that GR3 is directed against the alpha 3 integrin chain, whereas GR4 is directed against the beta 1 chain. These studies also indicate that some of the alpha 2 integrin chains on keratinocytes may be associated with a beta-chain not recognized by the antisera against the beta 1 integrin chain used in this study. PMID- 8192655 TI - Characteristics of bile salt uptake into skate hepatocytes. AB - The substrate specificity for the transporter that mediates the hepatic uptake of organic anions in freshly isolated hepatocytes of the elasmobranch little skate (Raja erinacea) was determined for bile salts and bile alcohols. The Na(+) independent transport system exhibits a substrate specificity, which is different from the specificity of Na(+)-dependent bile salt transport in mammals. Unconjugated and conjugated di- and tri-hydroxylated bile salts inhibit uptake of cholyltaurine and cholate competitively. Inhibition is significantly greater with unconjugated as opposed to glycine- or taurine-conjugated bile salts. However, the number of hydroxyl groups in the steroid moiety of the bile salts has only minor influences on the inhibition by the unconjugated bile salts. Since the transport system seems to represent an archaic organic-anion transport system, other anions, such as dicarboxylates, amino acids and sulphate, were also tested, but had no inhibitory effect on bile salt uptake. To clarify whether bile alcohols, the physiological solutes in skate bile, share this transport system, cholyltaurine transport was studied after addition of 5 beta-cholestane-3 beta,5 alpha,6 beta-triol, 5 alpha-cholestan-3 beta-ol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. These bile alcohols inhibit cholyltaurine uptake non competitively. In contrast, uptake of 5 beta-cholestane-3 alpha,7 alpha,12 alpha triol, which is Na(+)-independent, is not inhibited by cholyltaurine. The findings further characterize a Na(+)-independent organic-anion transport system in skate liver cells, which is not shared by bile alcohols and has preference for unconjugated lipophilic bile salts. PMID- 8192656 TI - Rat liver mitochondrial ADP-ribose pyrophosphatase in the matrix space with low Km for free ADP-ribose. AB - A study involving markers of subcellular and submitochondrial fractions, gradient centrifugation, latency measurements and extraction with digitonin, demonstrates the association of a specific ADP-ribose pyrophosphatase with rat liver mitochondria and its localization in the matrix space. The enzyme hydrolyses ADP ribose to AMP, with a Km of 2-3 microM. The results support the occurrence of a specific turnover pathway for free ADP-ribose and its relevance in mitochondria. PMID- 8192657 TI - Blue shifts in bacteriochlorophyll absorbance correlate with changed hydrogen bonding patterns in light-harvesting 2 mutants of Rhodobacter sphaeroides with alterations at alpha-Tyr-44 and alpha-Tyr-45. AB - A combination of Fourier-Transform (FT) resonance Raman spectroscopy and site directed mutagenesis has been used to examine the function of two highly conserved aromatic residues, alpha-Tyr-44 and alpha-Tyr-45, in the light harvesting 2 (LH2) complex of the photosynthetic bacterium Rhodobacter sphaeroides. In LH2 complexes, aromatic residues located at positions alpha-44 and alpha-45 are thought to be located near the putative binding site for bacteriochlorophyll, and alterations at these positions are known to produce blue shifts in bacteriochlorophyll absorbance. In the present work, mutant LH2 complexes carrying the alterations alpha-Tyr-44-->Phe, alpha-Tyr-45-->Phe and alpha-Tyr-44,-45-->Phe,Leu were examined. FT resonance Raman spectroscopy of the resulting complexes shows the breakage of a hydrogen bond to the 2-acetyl carbonyl group of one of the B850 bacteriochlorophylls in the LH2 complex; in the double mutant, breakage of a second bond is probable. These results suggest that one of these hydrogen bonds is to alpha-Tyr-44, placing this residue in close proximity to ring I of one of the B850 bacteriochlorophyll a pigments. The breakage of one, then two, 2-acetyl carbonyl hydrogen bonds correlates well with the shift in the absorbance of the B850 pigments of 11 nm then 26 nm at 77 K. Thus a consistency between literature theoretical calculations and the observations from both absorption and FT resonance Raman spectroscopy is demonstrated. PMID- 8192658 TI - Stimulation of phospholipase D in rabbit platelet membranes by nucleoside triphosphates and by phosphocreatine: roles of membrane-bound GDP, nucleoside diphosphate kinase and creatine kinase. AB - Previous work has shown that guanosine 5'-[gamma-thio]triphosphate (GTP[S]) and GTP stimulate phospholipase D (PLD) in rabbit platelet membranes and that these effects are greatly enhanced by pretreatment of platelets with phorbol esters that activate protein kinase C [Van der Meulen and Haslam (1990), Biochem. J. 271, 693-700]. In the present study, the effects of Mg2+, various nucleoside triphosphates and phosphocreatine (PCr) were investigated. Platelet membranes containing phospholipids labelled with [3H]glycerol were assayed for PLD in the presence of an optimal Mg2+ concentration (10 mM) by measuring [3H]phosphatidylethanol formation in incubations that included 300 mM ethanol. In membranes from phorbolester-treated platelets, the same maximal increases in PLD activity (5-fold) were seen with 1 microM GTP[S]), and 100 microM GTP. Addition of adenosine 5'-[gamma-thio]triphosphate (ATP[S]), ITP, XTP, UTP and CTP had similar stimulatory effects, but only at > or = 1 mM. In contrast, ATP had a biphasic action, causing a maximal (2-fold) stimulation at 10 microM and smaller effects at higher concentrations; the inhibitory component of the action of ATP was blocked by 2 microM staurosporine. Guanosine 5'-[beta-thio]diphosphate decreased the stimulatory effects of ATP and ATP[S]. UDP, which can inhibit nucleoside diphosphate kinase (NDPK), decreased the activation of PLD by ATP[S], ATP, XTP, CTP and to a lesser extent ITP, but had no effect on the actions of GTP[S] and GTP. Rabbit platelet membranes contained NDPK and addition of [gamma 32P]ATP led to the formation of [32P]GTP in amounts sufficient to explain most or all of the activation of PLD; UDP prevented GTP formation. PCr (0.04-1 mM) also stimulated membrane PLD activity, an effect that was dependent on endogenous membrane-bound creatine kinase (CK). UDP and guanosine 5'-[beta-thio]diphosphate each inhibited this effect of PCr. The results show that in rabbit platelet membranes, CK, NDPK and the GTP-binding protein that activates PLD can be functionally coupled. However, assay of membrane preparations at increasing dilutions showed that stimulation of PLD by the compounds studied, with the partial exception of ATP[S], involved diffusible rather than protein-bound intermediates. PMID- 8192659 TI - Immunological analysis of developmental changes in ecdysone 20-mono-oxygenase expression in the cotton leafworm, Spodoptera littoralis. AB - The developmental changes in ecdysone 20-mono-oxygenase during the sixth larval instar of the cotton leafworm, Spodoptera littoralis, were investigated. The specific activity of mitochondrial ecdysone 20-mono-oxygenase in the fat-body exhibited a distinct peak at 72 h, at which time the larvae stop feeding. Immunoblot analyses, using antibodies raised against components of vertebrate mitochondrial steroidogenic enzyme systems [anti-(cytochrome P-450scc), anti (cytochrome P-450(11) beta), anti-adrenodoxin and anti-(adrenodoxin reductase) antibodies], revealed the presence of specific immunoreactive polypeptides in fat body mitochondrial extracts. In addition, these antibodies effectively inhibited fat-body mitochondrial ecdysone 20-mono-oxygenase activity. This suggests that the S. littoralis steroid-hydroxylating system(s) may contain polypeptide components analogous to those present in vertebrates. A close correlation between developmental changes in mitochondrial ecdysone 20-mono-oxygenase activity and the abundance of polypeptides (approx. 66 kDa and 50 kDa) recognized by the anti (cytochrome P-450(11) beta) antibody and a polypeptide (approx. 52 kDa) recognized by the anti-(adrenodoxin reductase) antibody were observed in both fat body and midgut. These results suggest that developmental changes in the abundance of components of the ecdysone 20-mono-oxygenase system may play an important role in the developmental regulation of the enzyme expression and, hence, of 20-hydroxyecdysone titre. PMID- 8192660 TI - Effect of cyclodextrins and undigested starch on the loss of chenodeoxycholate in the faeces. AB - Starch that escapes digestion in the small intestine increases the elimination of chenodeoxycholate and its metabolites in the faeces of both mice and hamsters. In contrast, the elimination of cholate and its metabolites is not increased. In vitro, the affinity of starch for chenodeoxycholate is about 90-fold greater than for cholate. beta-Cyclodextrin, which approximates to one turn of the helical structures formed by the 1,4-linked glucose units of starch, shares these properties. It is proposed that these helical structures in starch act as binding sites for bile salts. PMID- 8192661 TI - Inhibition of hepatic gluconeogenesis by nitric oxide: a comparison with endotoxic shock. AB - Isolated hepatocytes incubated in the presence of the NO donors S-nitroso-N acetylpenicillamine (SNAP) and 3-morpholino-sydnonimine (SIN-1) displayed a time- and dose-dependent inhibition of glucose synthesis from lactate plus pyruvate as the substrate which correlated with NO production, but not nitrite production. Neither the parent compound of SNAP, N-acetyl-DL-penicillamine (NAP), nor nitrite or nitrate had any significant effect on glucose output, indicating that the inhibition was due to the generation of NO within the incubation medium. The concentrations of NO required for this effect (< 800 nM) are within the range reported to occur in intact tissues and in vivo. The magnitude of the inhibitory effect of SNAP (approximately 50%) was comparable with that of endotoxin treatment of the rat with lactate plus pyruvate as the substrate. When the effect of SNAP on glucose synthesis and lactate plus pyruvate synthesis from a number of different substrates was examined, this showed a pattern comparable with that observed after endotoxin treatment of the rat, suggesting that NO may be the inhibitory mediator of the effects of bacterial endotoxin on hepatic gluconeogenesis. The NO donor had no effect on the flux through 6-phosphofructo-1 kinase, supporting the concept that the primary site of inhibition of gluconeogenesis by both NO and endotoxin resides at the level of phosphoenolpyruvate formation. PMID- 8192662 TI - The fatty acids in unremodelled trypanosome glycosyl-phosphatidylinositols. AB - Glycolipid A, the precursor of the glycosyl-phosphatidylinositol (GPI) anchor of the trypanosome variant surface glycoprotein, is constructed in two phases. First, the glycan is assembled on phosphatidylinositol (PI), yielding a glycolipid termed A'. Second, glycolipid A' undergoes fatty acid remodelling, by deacylation and reacylation, to become the dimyristoyl species glycolipid A. In this paper, we examine the fatty acid content of glycolipid A' and its cellular progenitors. A' contains exclusively stearate at the sn-1 position and a complex mixture of fatty acids (including 18:0, 18:1, 18:2, 20:4 and 22:6) at sn-2. Presumably these fatty acids derive from stearate-containing PI species which initially enter the biosynthetic pathway. We compared the diacylglycerol species from glycolipid A' with those from phosphatidylinositol to determine whether a subset of stearate-containing PIs is utilized for GPI biosynthesis. We found that the spectrum of stearate-containing diacylglycerols in PI is similar to that in A', although the proportions of each compound differ. Total PI in general was highly enriched in stearate-containing species. Differences in composition between glycosylated PI and total cellular PI may be due to the substrate specificity of the sugar transferase which initiates the GPI biosynthetic pathway. Alternatively, the species of PI present at the endoplasmic reticulum site of GPI biosynthesis may differ from those in total PI. PMID- 8192663 TI - Synthesis of dehydrogenation polymers of ferulic acid with high specificity by a purified cell-wall peroxidase from French bean (Phaseolus vulgaris L.). AB - A cationic (pI 8.3) wall-bound peroxidase has been purified to homogeneity from suspension-cultured cells of French bean (Phaseolus vulgaris L.). The enzyme was a glycoprotein and its M(r) was 46,000 as determined by SDS/Page and h.p.l.c. gel filtration. It was localized biochemically to microsomes and the cell wall, and the latter subcellular distribution was confirmed by immunogold techniques. The native enzyme showed absorption maxima at 403, 500 and 640 nm, with an RZ (A405/A280) of 3.3. The peroxidase oxidized guaiacol and natural phenolic acids. By desorption-chemical-ionization mass spectrometry the enzyme was found to oxidize the model compound, ferulic acid, into dehydrodiferulic acid. Kinetics studies indicated an apparent Km of 113.3 +/- 22.9 microM and a Vmax of 144 mumol.min-1.nmol-1 of protein at an H2O2 concentration of 100 microM. In comparison with a second French-bean peroxidase (FBP) and horseradish peroxidase, as a model, it acted with a 6-10-fold higher specificity in this capacity. It is a member of the peroxidase superfamily of bacterial, fungal and plant haem proteins by virtue of its highly conserved amino acid sequence within the proximal and distal haem-binding sites. This is good evidence that this particular FBP may function in constructing covalent cross-linkages in the wall during development and response to pathogens. PMID- 8192664 TI - Insulin stimulation of glucose transport activity in rat skeletal muscle: increase in cell surface GLUT4 as assessed by photolabelling. AB - We have used a photoaffinity label to quantify cell surface GLUT4 glucose transporters in isolated rat soleus muscles. In this system, insulin stimulated an 8.6-fold increase in 3-O-methylglucose glucose transport, while photolabelled GLUT4 increased 8-fold. These results demonstrate that the insulin-stimulated increase in glucose transport activity in skeletal muscle can be accounted for by an increase in surface-accessible GLUT4 content. PMID- 8192665 TI - Cholate extracts of mitochondrial outer membranes increase inhibition by malonyl CoA of carnitine palmitoyltransferase-I by a mechanism involving phospholipids. AB - It has been reported that sodium cholate can separate the catalytic component of carnitine palmitoyltransferase-I (CPT-I) from a putative malonyl-CoA-binding regulatory protein capable of conferring sensitivity to malonyl-CoA on CPT-II. We found that cholate preferentially extracted a contaminating malonyl-CoA-sensitive CPT from mitochondrial inner membranes. When cholate extracts of outer membranes were incubated either with cholate extracts of inner membranes or with osmotically swollen mitochondria, inhibition of CPT by malonyl-CoA was increased. Treatment of intact mitochondria with subtilisin abolished the increased inhibition by malonyl-CoA, suggesting that the outer-membrane CPT-I was responsible for the increased inhibition. Incubation of cholate extracts with proteinase K did not prevent the increased inhibition. Fractionation of the cholate extract indicated the presence of phospholipids. Addition of cardiolipin or phosphatidylglycerol to osmotically swollen mitochondria increased sensitivity of CPT to malonyl-CoA, but several other phospholipids did not. When cardiolipin was added to intact mitochondria from either starved or fed rats, there were large increases in inhibition by malonyl-CoA; sensitivity in mitochondria from starved rats increased to that normally observed with mitochondria from fed rats. These results suggest that phospholipids are responsible for the increased inhibition of CPT by malonyl-CoA with added cholate extracts and that changes in membrane composition may be involved in the physiological regulation of CPT-I. PMID- 8192666 TI - Functional expression of the nitrobenzylthioinosine-sensitive nucleoside transporter of human choriocarcinoma (BeWo) cells in isolated oocytes of Xenopus laevis. AB - Cultured human choriocarcinoma (BeWo) cells have previously been shown to exhibit, in comparison with other cultured cell types, elevated nitrobenzylthioinosine (NBMPR)-sensitive transport activity and large numbers (> 10(7)/cell) of high-affinity NBMPR-binding sites [Boumah, Hogue and Cass (1992) Biochem. J. 288, 987-996]. The present study investigates whether NBMPR-sensitive nucleoside transport activity could be induced in Xenopus laevis oocytes by microinjection of poly(A)+ RNA isolated from proliferating cultures of BeWo cells. Expression of uridine transport activity was assayed by comparing rates of uptake (22 degrees C) of 100 microM [3H]uridine by RNA-injected oocytes with uptake by water-injected or uninjected oocytes. A 4-fold stimulation of uridine uptake (2.0 versus 0.5 pmol/90 min per oocyte) was seen when oocytes were injected with 50 ng of BeWo poly(A)+ RNA, and this stimulation was abolished when the RNA-injected oocytes were assayed in the presence of 10 microM NBMPR. The expressed uridine transport activity in oocytes was highly sensitive to NBMPR, with a 50% reduction seen at 1.1 nM NBMPR (IC50 value). The IC50 value for NBMPR inhibition of uptake of 100 microM [3H]uridine by intact BeWo cells was 1.4 nM. Inward fluxes of [3H]uridine in the RNA-injected oocytes were greatly reduced in the presence of high concentrations (2 mM) of non-radioactive nucleosides (adenosine, thymidine, inosine) that are known permeants of NBMPR-sensitive nucleoside transport processes. These results establish that the abundance of NBMPR-sensitive nucleoside transporter mRNA in poly(A)+ RNA preparations from BeWo cells is sufficient to achieve production of functionally active transporter protein in Xenopus oocytes and that, when expressed in Xenopus oocytes, the transporters exhibit NBMPR sensitivity and permeant selectively similar to that of the native transporters. PMID- 8192667 TI - ADP-ribosylation of the GTP-binding protein Rho by Clostridium limosum exoenzyme affects basal, but not N-formyl-peptide-stimulated, actin polymerization in human myeloid leukaemic (HL60) cells. AB - Treatment of human myeloid leukaemic (HL60) cells with Clostridium limosum exoenzyme, which inactivates the small GTP-binding protein Rho by ADP ribosylation, decreased the basal F-actin content. Inhibition of F-actin occurred after long-term treatment (24 h) of intact HL60 cells or after introduction of the toxin by electropermeabilization in a toxin-concentration-dependent manner. Concomitantly with the decrease in the basal F-actin content, the GTP-binding protein Rho was ADP-ribosylated in intact cells. However, Clostridium limosum toxin had no inhibitory effect on N-formyl-peptide-induced actin polymerization. Moreover, the relative N-formyl-peptide-stimulated polymerization was substantially enhanced in cells treated with Clostridium limosum transferase. In contrast with Clostridium limosum exoenzyme, component C21 of the Clostridium botulinum C2 toxin, which ADP-ribosylates G-actin, depolymerized basal F-actin and inhibited N-formyl-peptide-induced actin polymerization in electropermeabilized HL60 cells. These findings indicate that Rho proteins are involved in the basal, but not the ligand-evoked, actin polymerization in HL60 cells. PMID- 8192668 TI - The secreted cathepsin L-like proteinases of the trematode, Fasciola hepatica, contain 3-hydroxyproline residues. AB - The cysteine proteinases synthesized by the adult stage of the trematode Fasciola hepatica were found to be a very heterogeneous group of proteins as demonstrated by one- and two-dimensional gel analyses. N-terminal amino acid sequencing indicated the presence of at least two distinct gene products among the secreted cysteine proteinases. Enzymic studies and peptide sequence analysis of the excreted/secreted cysteine proteinases suggested a close relationship to the plant thiol cathepsins and the mammalian cathepsin L subfamily. The cloning of a representative cDNA for a putative Fasciola cathepsin confirmed similarities to the cathepsin L subfamily but revealed low identity with the cathepsin-like proteinases of the related trematode, Schistosoma, nematode cathepsins and the mammalian cathepsin B subfamily. Furthermore, peptide and protein sequencing revealed the modification of certain highly conserved prolines to unusual 3 hydroxyproline derivatives. This is the first report of modified prolines in any proteinase. This finding, as well as the high activities of these cathepsins at neutral to alkaline pH values, raises a number of questions as to the physiological function of these thiol cathepsins and their interaction with host tissues. PMID- 8192669 TI - Inhibitors of serine/threonine phosphatases enhance phosphorylation of the interferon-gamma receptor while selectively attenuating interferon-gamma-induced gene expression in human peripheral-blood monocytes. AB - Since many events following ligand-induced receptor clustering are controlled by serine and threonine (Ser/Thr) phosphorylation, we initiated an investigation into the role of Ser/Thr phosphatases in both phosphorylation of the interferon gamma (IFN-gamma) receptor and IFN gamma-induced gene expression in human peripheral-blood monocytes. Whereas IFN gamma alone did not enhance phosphorylation of the IFN gamma receptor, treatment of monocytes with the Ser/Thr phosphatase inhibitors, okadaic acid and calyculin A, resulted in increased phosphorylation of the IFN gamma receptor. However, when these cells were analysed for IFN gamma-induced IP-10 gene expression, there was profound inhibition. Using three IFN gamma-induced early-response genes, IP-10, the Fc gamma receptor type I (Fc gamma RI) and ISG-54, we found selective sensitivity to pretreatment with okadaic acid and calyculin A. Whereas IFN gamma induction of IP 10 was blocked by both inhibitors, only calyculin A prevented Fc gamma RI-gene expression. Neither inhibitor prevented ISG-54 induction by IFN gamma. IFN-gamma activated formation of the DNA-binding-protein complex FcRF gamma (which binds to the promoter of the Fc gamma RI gene) remained unaffected by okadaic acid or calyculin A. Therefore these data suggest that Ser/Thr phosphatases have no major part in IFN gamma-initiated signal transduction across the membrane, but selectively control the ultimate transcription of a set of early-response genes. PMID- 8192670 TI - Bacterial morphine dehydrogenase further defines a distinct superfamily of oxidoreductases with diverse functional activities. AB - Pseudomonas putida morphine dehydrogenase is shown to be closely homologous to 18 proteins, defining a superfamily within which morphine dehydrogenase particularly resembles two bacterial, 2,5-dioxo-D-gluconic acid reductases, and two eukaryotic proteins of unknown functions. Relationships within the superfamily are extensive and complex. Residue identities between protein pairs range from 29-90%. Three subgroups are proposed. Nevertheless, on the basis of residue conservations/exchanges it is suggested that the nicotinamide coenzyme binding and substrate reduction occur in all the enzymes by broadly analogous mechanisms, among which some probable differences are identified. PMID- 8192671 TI - The role of cysteine residues in glucose-transporter-GLUT1-mediated transport and transport inhibition. AB - The role of cysteine residues in transport function of the glucose transporter GLUT1 was investigated by a mutagenesis-expression strategy. Each of the six cysteine residues was individually replaced by site-directed mutagenesis. Expression of the heterologous wild-type or mutant glucose transporters and transport measurements at two hexose concentrations (50 microM and 5 mM) were undertaken in Xenopus oocytes. The catalytic activity of GLUT1 was retained, despite substitution of each single cysteine residue, which indicated that no individual residue is essential for hexose transport. This finding questions the involvement of oligomerization or intramolecular stabilization by a single disulphide bond as a prerequisite for transporter activation under basal conditions. Application of the impermeant mercurial thiol-group-reactive reagent p-chloromercuribenzenesulphonate (pCMBS) to the external or internal surface of plasma membrane demonstrated that cysteine-429, within the sixth external loop, and cysteine-207, at the beginning of the large intracellular loop which connects transmembrane segments 6 and 7, are the residues which are involved in transport inhibition by impermeant thiol-group-reactive reagents from either side of the cell. These data support the predicted membrane topology of the transport protein by transport measurements. If residues other than the cysteines at positions 429 or 207 are exposed to either side of the plasma membrane by conformational changes, they do not contribute to the transport inhibition by pCMBS. Application of pCMBS to one side of the plasma membrane also inhibited transport from the opposite direction, most likely due to the hindrance of sugar-induced interconversion of transporter conformation. PMID- 8192672 TI - Interaction of transferrin and its iron-binding fragments with heparin. AB - The interaction of heparin with transferrin (Tf; bovine and rat) and the isolated iron-binding lobes of bovine Tf were investigated. Affinity chromatography of rat Tf on heparin-agarose showed that interaction depended on both the iron content of Tf and the pH of the medium. Both the iron-free and iron-saturated forms of Tf were strongly bound by the column at pH 5.6, but only the iron-free form revealed significant affinity at pH 7.4. Desialylation of Tf moderately promoted interaction, treatment with cyclohexanedione moderately reduced interaction, and succinylation abolished it altogether. In the presence of heparin, iron release from the N-terminal lobe of native bovine Tf was accelerated and from the C terminal lobe it was slightly reduced. The heparin effect remained qualitatively the same on each lobe after their separation by tryptic digestion and DEAE cellulose chromatography. The affinity of native bovine Tf for heparin was very close to that of its isolated N-terminal lobe, thus suggesting that it is this portion of the molecule that binds to the glycosaminoglycan. It is concluded that the consequences for iron-binding strength of the two transferrin lobes are diagonally opposite when Tf is bound to heparin as opposed to its natural cell surface receptor. PMID- 8192673 TI - Dietary omega-3 and polyunsaturated fatty acids modify fatty acyl composition and insulin binding in skeletal-muscle sarcolemma. AB - Feeding animals with diets high in saturated fat induces insulin resistance, and replacing saturated fat isocalorically with poly-unsaturated fat, especially long chain omega-3 fatty acids, will prevent the development of insulin resistance in skeletal-muscle tissue. To investigate the mechanism, rats were fed on high-fat (20%, w/w) semipurified diets for 6 weeks. Diets containing ratios of polyunsaturated/saturated (P/S) fatty acid of 0.25 (low-P/S diet) and 1.0 (high P/S diet) were used to study the effect of the level of saturated fat. To study the effects of omega-3 fatty acids, diets with a low-P/S ratio containing either 0 (low-omega-3 diet) or 3.3% (high-omega-3 diet) long-chain omega-3 fatty acids from fish oil were fed. Plasma membrane from skeletal muscle was purified. The content of fatty acids in sarcolemmal phospholipid was significantly related to the dietary composition. Insulin binding to intact sarcolemmal vesicles prepared from rats fed on diets high in omega-3 fatty acids increased 14-fold compared with animals fed on the low-omega-3 diet (P < 0.0001). Feeding rats on a diet with a high P/S ratio increased sarcolemmal insulin binding by 2.3-fold (P < 0.05). Increased insulin binding was due to increased receptor number at the low affinity high-capacity binding site. Dietary effects on insulin binding were eliminated when studies were carried out on detergent-solubilized membranes, indicating the importance of the phospholipid fatty acyl composition for insulin binding. The results suggest that dietary omega-3 and polyunsaturated fatty acids increase insulin binding to sarcolemma by changing the fatty acyl composition of phospholipid surrounding the insulin receptor, and this might be the mechanism by which dietary fatty acids modify insulin action. PMID- 8192674 TI - A new dopachrome-rearranging enzyme from the ejected ink of the cuttlefish Sepia officinalis. AB - A melanogenic enzyme catalysing the rearrangement of dopachrome has been identified in the ejected ink of the cuttlefish Sepia officinalis. This enzyme occurs as a heat-labile protein which co-migrates with tyrosinase under a variety of chromatographic and electrophoretic conditions. On SDS/PAGE it shows like a single band with an approx. molecular mass of 85 kDa. The enzyme possesses high substrate specificity, acting on L-dopachrome (Km = 1 mM at pH 6.8) and on L alpha-methyl-dopachrome, but not on D-dopachrome, L-dopachrome methyl ester, dopaminochrome and adrenochrome. Significant inhibition of the catalytic activity was observed with tropolone and L-mimosine. H.p.1.c. analysis of the enzyme catalysed rearrangement of L-dopachrome revealed the quantitative formation of the decarboxylated product, 5,6-dihydroxyindole. These results point to marked differences between melanogenesis in cephalopod pigment cells and in melanocytes, which may have important implications in relation to the use of sepiomelanin as a model for studies of mammalian melanins. PMID- 8192675 TI - Permissive stimulation of Ca(2+)-induced phospholipase A2 by an adenosine receptor agonist in a pertussis toxin-sensitive manner in FRTL-5 thyroid cells: a new 'cross-talk' mechanism in Ca2+ signalling. AB - We have described the pertussis toxin (PTX)-sensitive potentiation of P2 purinergic agonist-induced phospholipase C activation, Ca2+ mobilization and arachidonic acid release by an adenosine receptor agonist, N6-(L-2 phenylisopropyl)adenosine (PIA), which alone cannot influence any of these cellular activities [Okajima, Sato, Nazarea, Sho and Kondo (1989) J. Biol. Chem. 264, 13029-13037]. In the present study we have found that arachidonic acid release was associated with lysophosphatidylcholine production, and conclude that arachidonic acid is produced by phospholipase A2 in FRTL-5 thyroid cells. This led us to assume that PIA augments P2-purinergic arachidonic acid release by increasing [Ca2+]i which, in turn, activates Ca(2+)-sensitive phospholipase A2. The arachidonic acid-releasing response to PIA was, however, always considerably higher (3.1-fold increase) than the Ca2+ response (1.3-fold increase) to the adenosine derivative. In addition, arachidonic acid release induced by the [Ca2+]i increase caused by thapsigargin, an endoplasmic-reticulum Ca(2+)-ATPase inhibitor, or calcium ionophores was also potentiated by PIA without any effect on [Ca2+]i and phospholipase C activity. This action of PIA was also PTX sensitive, but not affected by the forskolin- or cholera toxin-induced increase in the cellular cyclic AMP (cAMP), suggesting that a PTX-sensitive G-protein(s) and not cAMP mediates the PIA-induced potentiation of Ca(2+)-generated phospholipase A2 activation. Although acute phorbol ester activation of protein kinase C induced arachidonic acid release, P2-purinergic and alpha 1-adrenergic stimulation of arachidonic acid release was markedly increased by the protein kinase C down-regulation caused by the phorbol ester. This suggests a suppressive role for protein kinase C in the agonist-induced activation of arachidonic acid release. We conclude that PIA (and perhaps any of the G1-activating agonists) augments an agonist (maybe any of the Ca(2+)-mobilizing agents)-induced arachidonic acid release by activation of Ca(2+)-dependent phospholipase A2 in addition to enhancement of agonist-induced phospholipase C followed by an increase in [Ca2+]i. PMID- 8192676 TI - Mechanism of inhibition of protein kinase C by 14-3-3 isoforms. 14-3-3 isoforms do not have phospholipase A2 activity. AB - The ability of individual members of the 14-3-3 protein family to inhibit protein kinase C (PKC) has been studied by using a synthetic peptide based on the specific 80 kDa substrate for PKC (MARCKS protein) in two different assay systems. Recombinant 14-3-3 and isoforms renatured by a novel method after separation by reverse-phase h.p.l.c. were studied. The detailed effects of diacylglycerol and the phorbol ester phorbol 12-myristate 13-acetate on the inhibition were also investigated. This suggests that one of the sites of interaction of 14-3-3 may be the cysteine-rich (C1) domain in PKC. Since a region in secreted phospholipase A2 (PLA2) shares similarity with this domain, the ability of 14-3-3 to interact with mammalian PLA2 was studied. Cytosolic PLA2 has some similarity to the C2 region of PKC, and the effect of 14-3-3 on this class of PLA2 was also analysed. In contrast with a previous report, no PLA2 activity was found in brain 14-3-3, nor in any of the recombinant proteins tested. These include zeta 14-3-3 isoform, on which the original observation was made. PMID- 8192677 TI - Phosphorylation of calmodulin on Tyr99 selectively attenuates the action of calmodulin antagonists on type-I cyclic nucleotide phosphodiesterase activity. AB - Tyr99 phosphorylation of calmodulin appears to induce a distinct conformational change as is evident from the profound attenuation of the Ca(2+)-induced enhancement of calmodulin's mobility seen during SDS/PAGE. The effect of this conformational change appears to be localized, in that both calmodulin and P Tyr99-calmodulin show identical dose-dependent activation profiles for stimulation of a physiological effector, type-I (Ca2+/calmodulin-stimulated) cyclic nucleotide phosphodiesterase (PDE) activity and their presence engenders similar dose-dependent PDE activation by Ca2+. In marked contrast with this, with P-Tyr99-calmodulin there were 3-4-fold increases in the IC50 values for inhibition of type-I PDE activity by the calmodulin antagonists TFP and W7, together with increased values for Hill coefficients for inhibition. The polybasic compound poly(L-lysine) potently augmented the action of calmodulin as a PDE activator, causing an approx. 7-fold decrease in the EC50 value for activation of PDE. It is suggested (i) that the Tyr99 phosphorylation of calmodulin, which occurs within a high-affinity Ca(2+)-binding domain, induces a localized conformational change in this peptide which can selectively attenuate the action of calmodulin antagonists on type-I PDE activity while leaving unaffected Ca(2+)-dependent activation, and (ii) that polybasic substances on complexing with calmodulin may serve to enhance the sensitivity of type-I PDE to activation by this regulatory peptide. PMID- 8192678 TI - Uptake of protoporphyrin and continuous spectrophotometric assay for magnesium chelatase in Rhodobacter spheroides. AB - Uptake of protoporphyrin was shown by Rhodobacter spheroides under anaerobic conditions in the dark. The process was not energy-dependent but required EGTA and was markedly stimulated by Methyl Viologen. Kinetic studies were consistent with a saturable process with Kd = 5-10 microM and Bmax. = 2.2 nmol of protoporphyrin bound/mg dry weight of cells. Bound protoporphyrin could be converted into magnesium protoporphyrin monomethyl ester under anaerobic conditions in the light or at low pO2 (6.3%) in the dark. This formed the basis of a sensitive continuous spectrophotometric assay for magnesium chelatase, which avoids the need to extract the product into organic solvent, and may facilitate the development of a cell-free system for magnesium chelatase in photosynthetic bacteria. It is proposed also that the uptake mechanism shown for exogenous protoporphyrin may indicate the existence of a ligand or carrier system for endogenously produced protoporphyrin essential for magnesium chelatase activity. PMID- 8192679 TI - Interaction of skeletal-muscle myosin subfragment-1 with the actin-(338-348) peptide. AB - The data presented here confirm and provide further experimental evidence that rabbit skeletal-muscle myosin subfragment-1 (S-1) binds to the postulated actin (338-348) hydrophobic segment [Kabsch, Mannherz, Suck, Pai and Holmes (1990) Nature (London) 347, 37-44] with high affinity in the absence and presence of MgATP. The apparent dissociation constant of the S-1 interaction (5.5 x 10(-7) M) with the actin-(338-348) peptide was of the same order of magnitude as that of the actin-(18-28) binding site (2 x 10(-6) M). In similar conditions, fragmented (27 kDa-50 kDa-20 kDa) S-1 also bound to the peptide. Antibodies directed to the vicinal sequence 348-358 were rapidly eliminated from actin by S-1 interaction and weakened S-1 binding to monomeric or filamentous actin. The antigenic site (348-358) is located very close to the C-terminal S-1-binding site (360-369) and encompasses some residues (Leu-349 and Phe-352) included in the hydrophobic S-1 binding region [Schroder, Manstein, Jahn, Holden, Rayment, Holmes and Spudich (1993) Nature (London) 364, 171-174]. It was observed that anti-[actin-(348-358)] antibodies were also unable to decrease actomyosin ATPase activity, in contrast with previous results obtained with anti-[actin-(18-28)] antibodies [Adams and Reisler (1993) Biochemistry 32, 5051-5056]. The hydrophobic actin-(338-348) peptide used in considerable excess was unable to perturb acto-S-1 and S-1 activities in contrast with results obtained with the N-terminal actin peptide [Kogler, Moir, Trayer and Ruegg (1991) FEBS Lett. 294, 31-34]. PMID- 8192680 TI - Hepatic lipase may act as a ligand in the uptake of artificial chylomicron remnant-like particles by isolated rat hepatocytes. AB - Active and heat-inactivated hepatic lipase stimulated to a statistically comparable extent the uptake of chylomicron remnant-like particles by isolated rat hepatocytes by 3-fold and 2.3-fold respectively and, likewise, their binding to hepatic plasma membranes by 5-fold and 4-fold respectively. Hepatic lipase may facilitate uptake of these particles, not only as a lipolytic enzyme, but also as a ligand anchored to extracellular glycosaminoglycans. PMID- 8192681 TI - Purification and properties of porphobilinogen deaminase from Arabidopsis thaliana. AB - Porphobilinogen deaminase (EC 4.3.1.8) has been purified to homogeneity (16,000 fold) from the plant Arabidopsis thaliana in yields of 8%. The deaminase is a monomer of M(r) 35,000, as shown by SDS/PAGE, and 31,000, using gel-filtration chromatography. The pure enzyme has a Vmax. of 4.5 mumol/h per mg and a Km of 17 +/- 4 microM. Determination of the pI and pH optimum revealed values of 5.2 and 8.0 respectively. The sequence of the N-terminus was found to be NH2 XVAVEQKTRTAI. The deaminase is heat-stable up to 70 degrees C and is inhibited by NH3 and hydroxylamine. The enzyme is inactivated by arginine-, histidine- and lysine-specific reagents. Incubation with the substrate analogue and suicide inhibitor, 2-bromoporphobilinogen, results in chain termination and in inactivation. PMID- 8192682 TI - Components of drug dependence: reinforcement, discrimination and adaptation. AB - A general scheme of addiction should attempt to provide a unifying framework that links together the many dimensions of the problem. Dependence is manifested in the molecular, cellular and neural systems, and at the behavioural, cognitive and social levels. The approach presented in this paper regards drug-seeking behaviour as the main common element in all drug addictions and sees changes in this behaviour as the ultimate end-point for preventative and therapeutic measures. The multifactor model (Fig. 1) stresses the importance of rewarding, discriminative and aversive effects of drugs that interact with genetic and environmental factors to produce drug-seeking behaviour. The analysis of these effects can extend to studies not only of the psychological mechanisms, but also of associated neural mechanisms in terms of neurochemistry and neuroanatomy. Drug seeking behaviour involves repeated exposure to drugs that produce further adaptive changes that regulate subsequent intake. Studies on behavioural tolerance and sensitization show that the adaptive changes cannot be considered in isolation because the extent and nature of adaptation depends on the circumstances in which drugs are given. For example, environmental stimuli that have been associated with drug action in the past can exert a profound influence on individual reactions to addictive drugs. The model portrays the reinforcing and other related stimulus properties of drugs as malleable effects determined by many factors, from which it follows that the neurobiology of dependence is not the neurobiology of either acute or chronic exposure to drugs; it is the neurobiology of both single and repeated exposure to drugs under environmental and genetic conditions that lead to or are accompanied by drug-seeking behaviour. PMID- 8192683 TI - Opiate receptors--the historical breakthrough in drug research. AB - Morphine (Fig. 1) remains the most powerful analgesic but its therapeutic value is compromised by its strong reinforcing properties, making it highly addictive. This has stimulated the quest to find an analgesic lacking dependence-producing properties. So far no such drug has been discovered. However, this search has helped to disclose the large range of endogenous opioid peptides and the various receptors on which they act. This diversity and opportunity for interaction between exogenous drug and endogenous peptide, makes opiate dependence, tolerance and withdrawal complicated phenomena that are not fully understood at the molecular and cellular levels. The occurrence of opiate receptors in 'reward' pathways also makes them possible targets for the treatment of other addictions, adding a further dimension to the picture. PMID- 8192684 TI - Pharmacogenetic approaches to drug dependence. AB - The aim of this volume is to bring together information about both the neurochemical mechanisms associated with the actions of drugs of abuse and the psychopharmacological and behavioural effects of these drugs. One approach that is proving to be quite useful for bringing together these two very diverse fields is the use of classical pharmacogenetic techniques. Pharmacogenetics is defined as the study of genetic and environmental factors underlying individual differences in response to pharmacological or toxicological agents. Much of the early work in this field dealt with genetic differences in drug metabolism and other pharmacokinetic parameters [1]. More recently, however, attention has been directed towards understanding the implications of genetic differences associated with pharmacodynamic parameters mediating the actions of drugs. This paper discusses the use of pharmacogenetic techniques in drug abuse research. It presents an overview of some of the more common genetic techniques available for use in drug research and provides some examples from research projects that have employed these approaches. PMID- 8192685 TI - Animal models of alcoholism: genetic strategies and neurochemical mechanisms. AB - Evidence from human studies indicates that response to alcohol consumption and the probability of developing alcoholism have a heritable basis. The involvement of several genes encourages the application of classical genetics to elucidate the genetic basis of alcohol abuse. Quantitative genetics can provide evidence for modes of inheritance and estimates of gene number. Therefore, inbred strains and selective breeding programmes have been used to demonstrate a genetic basis for the physiological and behavioural effects of ethanol in rodents. Neurochemical studies have shown that ethanol has effects on membrane fluidity, and on membrane receptors, ion channels and enzymes (Fig. 1). Comparison of these in animal lines selected for a particular response (or lack of response) to ethanol has disclosed differences in membrane composition (notably in polysialogangliosides), and in the functioning of NaK-ATPase, Na+ channels and gamma-aminobutyric acid (GABAA) receptors. Not all of these effects were observed at relevant ethanol concentrations, but differences in the properties of GABAA receptors between lines are the most compelling. Thus classical genetic strategies, while labour intensive with respect to the generation and maintenance of animal lines, have proven useful in dissecting the molecular, cellular and behavioural effects of alcohol and their genetic variability. PMID- 8192686 TI - Adaptive changes in numbers of calcium channels in drug dependence. AB - Adrenal-derived cells in culture slowly upregulate numbers of putative calcium channel proteins in response to inhibitory drugs including ethanol, benzodiazepines and morphine. This appears to be an adaptive response to cell inhibition involving second messengers and protein phosphorylation and culminating in alterations in expression of the calcium channel gene (Fig. 1). These increases in calcium channels lead to rebound increases in cell excitability when the depressant drugs are withdrawn (a characteristic feature of chemical dependence on depressant drugs) so that this change in numbers of calcium channels may provide a model for one mechanism of chemical dependence. Similar findings have been reported in the brains of animals made dependent on depressant drugs, and genetic and pharmacological manipulations of dependence and withdrawal further support a role for calcium channels in these phenomena. PMID- 8192687 TI - Cannabinoid receptors: G-protein-mediated signal transduction mechanisms. AB - The recent discovery and cloning of cannabinoid receptors has provided a major breakthrough in the understanding of the biochemical mechanisms of action of delta 9-tetrahydrocannibinol (delta 9-THC). Cannabinoid receptors are coupled to G-proteins and inhibit adenylyl cyclase in a variety of systems. In the brain, cannabinoid-inhibited adenylyl cyclase and the receptors are particularly prevalent in the cerebellum, where they are localized to cerebellar granule cells (Fig. 1). In these cells, cannabinoid receptors are co-localized with other Gi/o linked receptors such as gamma-aminobutyric acid (GABAB) receptors, where they share common effector systems (adenylyl cyclase catalytic units) but not common G proteins. This sharing of effectors leads to the phenomenon of receptor convergence, in which agonists of different receptor types can produce the same biological response in certain cells. In cultured hippocampal neurons, cannabinoids also act through G-proteins to increase potassium conductance. In these cells, the predominant electrophysiological response at relatively low (microM) concentrations of cannabinoids is mediated through a voltage-sensitive potassium A current (IA) (Fig. 1). The action of cannabinoid receptors in this system is to shift the voltage sensitivity of IA channels to higher voltage ranges, thus increasing K+ conductance at lower membrane potentials and decreasing the probability of multiple action potentials. When combined with data from other groups showing a cannabinoid receptor-mediated decrease in calcium conductance, along with the unique localization of cannabinoid receptors in the brain, it is clear that these receptor-effector combinations are well situated to mediate many of the well-known neurobiological effects of delta 9-THC. PMID- 8192688 TI - Nicotine dependence--mechanisms and therapeutic strategies. AB - The current view among most researchers and clinicians is that habitual cigarette smoking is a form of dependence on nicotine. It is the central actions of nicotine that appear to be particularly important in this regard. Although multiple subtypes of nicotine receptor are expressed in the brain, attention has focused on a prevalent subtype (containing alpha 4 and beta 2 subunits) which is believed to represent the prime target for 'smoking doses' of nicotine. The mesolimbic dopamine system, a neuronal population which has been implicated in the reinforcing actions of certain drugs (e.g. amphetamine), also appears to mediate the reinforcing actions of nicotine in laboratory rats. Current pharmacotherapeutic approaches to smoking cessation rely on nicotine replacement. It is argued that the administration of a selective antagonist of central nervous system nicotine receptors (Fig. 1) may lead to higher long-term abstinence rates, and research strategies for the development of such a drug are outlined. PMID- 8192689 TI - Antiepileptics from gamma-aminobutyric acid. AB - The importance of GABAergic neurons as the control sites at the central excitation level is generally accepted. Recently, knowledge has expanded concerning the participation of the GABAergic system in the pathophysiology of neurological and psychiatric diseases. Especially the pathogenesis of epilepsy is seen in connection with a loss of neuronal inhibitory function. Investigations into the structure and biochemistry of the central inhibitory transmitter GABA (gamma-aminobutyric acid) and the GABAA receptor resulted in medicinal-chemical strategies to stimulate GABAergic neurotransmission. With the synthesis of the GABA derivatives progabide, vigabatrin and gabapentin, a very promising enrichment of antiepileptic pharmacotherapy has become available. PMID- 8192690 TI - Evidence against a significant implication of carbonic anhydrase inhibitory activity of zonisamide in its anticonvulsive effects. AB - To clarify whether the inhibitory effect of zonisamide (Excegran, CAS 68291-97-4) on carbonic anhydrase contributes to its anticonvulsant activity, the anticonvulsant activity of 7-methylated zonisamide, a zonisamide analogue which has the same potency of activity as zonisamide in inhibiting carbonic anhydrase in vitro, has been examined. The study using mice did not reveal 7-methylated zonisamide to have any anticonvulsant activity even though its brain concentration level was more than two times the minimal effective concentration of zonisamide. These findings indicate that the anticonvulsant effect of zonisamide is derived from a mechanism(s) other than inhibition of carbonic anhydrase. PMID- 8192691 TI - Preclinical toxicology studies with the new dopamine agonist pergolide. Acute, subchronic, and chronic evaluations. AB - Pergolide (LY127809, CAS 66104-23-2), a dopamine agonist for the treatment of Parkinson's disease, was evaluated for toxicity in acute, subchronic, and chronic studies. Acute toxicity tests using oral, intravenous and intraperitoneal routes were conducted in rats, mice, rabbits, and dogs. The acute oral median lethal doses (MLD) ranged from 8.4 to 33.6 mg/kg in Wistar and Fischer 344 rats, and from 54.0 to 87.2 mg/kg in ICR mice. Oral doses of 20 and 25 mg/kg produced no mortality in rabbits or dogs, respectively. The MLD by the iv route ranged from 0.59 to 0.87 mg/kg for Fischer 344 rats and from 11.6 to 37.1 mg/kg for ICR mice. The predominant signs of toxicity in the acute studies included hyperactivity, poor grooming, ptosis, aggressive behavior, increased gnawing activity, tremors, convulsions, and emesis. In the subchronic and chronic studies, Fischer 344 rats, B6C3F1 mice, and beagle dogs were administered pergolide either by gavage or in the diet for up to 1 year. Daily doses in these studies ranged up to 20 mg/kg for rats, 45 mg/kg for mice, and 5 mg/kg for dogs. The predominant treatment-related effects seen in these studies were attributable to the pharmacologic activity of pergolide. These consisted primarily of CNS-mediated clinical signs in rats and dogs, weight loss or decreased weight gain, emesis in dogs, and inhibition of lysis of corpora lutea with a corresponding increase in the weight of the uterus and ovaries. Pergolide treatment was not associated with any specific target organ toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192692 TI - Anti-atherosclerotic and plasma lipid lowering effects of the novel calcium blocker with alpha 1-adrenoceptor antagonistic activity, monatepil, in high cholesterol diet-fed Japanese Macaca fuscata monkeys. AB - 1. The preventive effects of atherosclerosis and hyperlipidemia of monatepil ([(+ )-N-(6,11-dihydrodibenzo [b,e]thiepin-11-yl)-4-(4-fluorophenyl)-1-piperazine butanamide+ + +]monomaleate , AJ-2615, CAS 103377-41-9), a new antihypertensive drug with potent calcium antagonistic and alpha 1-adrenoceptor blocking activities, were investigated in Japanese monkeys (Macaca fuscata) fed with a cholesterol-rich diet (2% cholesterol + 6% corn oil) and compared with those of prazosin. 2. The dose of monatepil selected (30 mg/kg/d, p.o., 6 months) was the plasma concentration dose level of antihypertensive therapy and that of prazosin (2 mg/kg twice daily, p.o., 6 months) was the dose where hypolipidemic effect in cholesterol-fed monkeys has been reported. 3. In the cholesterol diet control group (n = 7), plasma levels of total cholesterol and low-density lipoprotein (LDL) significantly increased and that of high-density lipoprotein-cholesterol (HDL-C) decreased compared with the normal diet group (n = 5). In the monatepil group (n = 5), these changes were significantly suppressed. In the prazosin group (n = 5), these changes were also inhibited but the inhibitory effect was weaker than in the monatepil group. 4. The cholesterol content and sudanophilic area in the aorta indicating atheromatous lesions in the cholesterol-diet fed control group were significantly higher than those in the normal diet control group. In the monatepil group, these changes were significantly suppressed whereas in the prazosin group these changes were partially inhibited. 5. In the histological study, aortic lesions characterized by aggregations of foam cells were observed in the cholesterol-diet control group, while there was little change in the monatepil group. The anti-atherogenic effect of prazosin was weaker than that of monatepil. 6. Coronary atheromatous lesions were found in 4 out of the 7 animals in the cholesterol-diet control group and 3 out of the 5 animals in prazosin group. In contrast, no coronary atheromatous lesion was found in the monatepil group. 7. The treatment with monatepil did not influence food consumption, body weight, physical signs or blood biochemistry. 8. The anti-atherosclerotic and plasma lipid-lowering effects of monatepil may in part be attributable to its calcium antagonistic, alpha 1-adrenoceptor blocking, and anti-lipid peroxidation activities. 9. In conclusion, monatepil is a new class of antihypertensive agent that possesses anti-atherogenic properties and the ability to reduce plasma lipid levels, a main risk factor for atherosclerosis. PMID- 8192693 TI - Effect of benidipine hydrochloride on regional blood flow of the adipose tissue in anesthetized rats. AB - The dihydropyridine calcium antagonist benidipine hydrochloride (benidipine, KW 3049, CAS 105979-17-7) was intravenously administered to rats under anesthesia with urethane to investigate the effect on regional blood flow in the brown adipose tissue. Benidipine was given at the dose of 100 or 300 micrograms/kg and regional blood flow was measured by the microsphere method. Blood flow in the brown adipose tissue significantly increased and vascular resistance significantly decreased 30 min after i.v. administration of benidipine at 100 or 300 micrograms/kg. The mean blood pressure significantly decreased in the benidipine 100 and 300 micrograms/kg groups and cardiac output significantly increased in the benidipine 300 micrograms/kg group. As i.v. administration of benidipine induced a significant increase of regional blood flow in the brown adipose tissue which consumes excess energy, this agent is expected to have anti obesity effect in obese animals. PMID- 8192694 TI - Effects of concurrent administration of flosequinan and digoxin on the pharmacokinetics of each drug. AB - The pharmacokinetic and pharmacodynamic effects of co-administration of flosequinan (BTS 49465, CAS 76568-02-0) and digoxin (CAS 20830-75-5) were investigated in 12 healthy volunteers. A 4-day, open, lead-in phase established the pharmacokinetics of flosequinan (100 mg on the first day and 50 mg for the next 3 days) and was followed by a 24-day open interaction phase. Digoxin was administered alone (0.75 mg for the first 3 days and 0.5 mg for the next 4 days) to establish steady-state pharmacokinetics and in combination with flosequinan (100 mg on the 8th day and 50 mg for the next 14 days with 0.5 mg digoxin daily), and finally digoxin alone (0.5 mg for the remaining 3 days). No statistically significant differences were observed for any of the pharmacokinetic parameters for flosequinan, its major metabolite BTS 53554, or digoxin when flosequinan and digoxin were administered alone or concomitantly, but the confidence intervals for differences were relatively wide. Overall diastolic blood pressure was significantly lowered by 10% with concomitant treatment compared with flosequinan monotherapy. There were no significant effects on overall heart rate or systolic blood pressure, although pre-dose heart rate was increased by 6% during concomitant administration compared with digoxin alone, and remained high and digoxin alone. Adverse events (headache, nausea and vomiting) were reported by 2 volunteers on digoxin and 5 on concomitant therapy. One volunteer was withdrawn during concomitant therapy because of severe headache and vomiting. The results from this study indicate that no pharmacokinetic interaction occurred during concomitant administration of flosequinan and digoxin in healthy volunteers. PMID- 8192695 TI - [Vasoselective, substance-specific actions of isradipine on the great arteries of hypertensives in comparison to metoprolol]. AB - The effects of isradipine (Lomir, CAS 75695-93-1) and metoprolol (CAS 37350-58-6) on geometry and arterial compliance of the arteria brachialis of 14 patients each with essential hypertension were compared acutely and after three months of therapy by means of pulsed Doppler sonography and the determination of pulse wave velocity. A calculation model was used that allowed to determine the drug specific effects on arterial diameter and compliance under isobaric conditions. Isradipine increased measured and isobaric diameter during short-term (p < 0.05) and long-term administration (p < 0.05) whereas metoprolol did not change it. Isradipine increased measured and isobaric compliance during short-term (p < 0.05) and long-term administration (p < 0.05). Metoprolol reduced measured compliance acutely (p < 0.01) and isobaric compliance acutely (p < 0.05) and long term (p < 0.05). Drug-specific effects on compliance were different during short term and long-term administration (p < 0.01); the diameter was influenced differently only during short-term administration (p < 0.05). These opposite drug effects on the A. brachialis are probably due to a vasoselective relaxation of smooth muscle in large arteries by isradipine and-in the case of metoprolol arterial constriction. The increase of arterial compliance by isradipine reduces very effectively the load on the heart and could form the basis for the improvement in the prognosis of the hypertensive patient. PMID- 8192696 TI - Evaluation of the mutagenicity of 1-hydrazino-4-(3,5-dimethyl-1-pyrazolyl) pyridazino[4,5-b]indole. AB - The mutagenic potential of 1-hydrazino-4-(3,5-dimethyl-1-pyrazolyl) pyridazino [4,5-b]indole(A80a, CAS 135561-93-2), a new antihypertensive agent, was investigated in 3 test systems, according to the current EC Guidelines: Ames test with strains TA1535, TA1537, TA98 and TA100, SCE (sister chromatid exchange) test in V79 cells and micronucleus test in Swiss mice. No indications for a mutagenic potential were detected in bacteria and mice; positive results were obtained in eukaryotic cells. The potential for inducing chromosome aberrations in eukaryotic cells will be studied. PMID- 8192697 TI - Biological effects of the new platelet-activating factor receptor antagonist (+) cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride. AB - SM-12502 ((+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl, CAS 119383-00 5) inhibited platelet-activating factor (PAF)-induced aggregation of rabbit and human platelets with IC50 values of 2.3 mumol/l and 4.7 mumol/l, respectively, but did not inhibit platelet aggregation induced by adenosine diphosphate, collagen, thrombin, arachidonic acid, U46619 (a thromboxane A2 agonist) or Ca2+ ionophore A23187 at concentrations up to 400 mumol/l. SM-12502 competitively antagonized 3H-PAF binding to rabbit platelets with an IC50 of 1.0 mumol/l. In contrast, the anti-PAF activity of the optical isomer SM-12501 ((-)-cis-3,5 dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl) was much weaker and its IC50 was more than 100 mumol/l. SM-12502 prevented PAF-induced death in mice with ID50 values of 4.8 mg/kg (i.v.) or 68.6 mg/kg (p.o.). In guinea pigs, SM-12502 inhibited PAF (0.1 micrograms/kg)-induced hemoconcentration with ID50 values of 1.9 mg/kg (i.v.) or 40.2 mg/kg (p.o.). In addition, SM-12502 inhibited PAF (10 ng/kg)-induced hypotension in rats with ID50 values of 2.0 mg/kg (i.v.) or 6.5 mg/kg (p.o.). The in vivo effects of SM-12501 were much weaker. Orally administered SM-12502 showed rapid absorption and a long duration of pharmacological activity in rats. SM-12502 afforded dose-dependent protection against anaphylactic death in mice with ID50 values of 18.4 mg/kg (i.v.) and 136 mg/kg (p.o.). It also inhibited endotoxin (E. coli 0.55:B5, 60 mg/kg)-induced death in mice, with ID50 values of 119 mg/kg (i.v.) and 182 mg/kg (p.o.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192698 TI - Study on the influence of food on the absorption of theophylline from a controlled-release preparation. AB - The possible influence of food and fat content of meals on the bioavailability and pharmacokinetics of a 350 mg sustained-release theophylline (CAS 58-55-9) preparation (Bronchoretard) was investigated after single-dose oral administration to 18 volunteers in a randomized 3-way cross-over design. The treatments investigating an administration of the test preparation in a fasting state, after a standard meal and after a high-caloric fat evening meal, according to the commonly applied rules, could be shown to be equivalent with respect to the amount of bioavailability (AUC) and the observed maximal concentrations (Cmax). Pharmacokinetic parameters describing sustained-release characteristics were not changed either to any relevant degree. As expected, the co administration of food resulted in a physiologically determined delay in absorption, which probably is not therapeutically relevant during long-term administration. PMID- 8192699 TI - [Binding capacity of ibuprofen to muscle proteins]. AB - From former studies it is well known, that ibuprofen (CAS 15687-27-1) binds to muscular tissue in a higher degree than to tendons or ligaments. It is not known, however, what constituents of muscle tissue are responsible for this binding. Therefore the binding capacity of ibuprofen to different muscular proteins was studied. Actin, actomyosin, myosin, myoglobin, tropomyosin, lecithin, and native human collagen type I were incubated with 14C-ibuprofen and the specific binding was measured in relation to the total radioactivity. It could be shown that ibuprofen binds most markedly to actin. This binding could be inhibited by pre incubation of ibuprofen with soluble actin. In comparison to the other proteins studied the specific binding of ibuprofen to actin was 4 to 5 times higher. As actin is a constituent of the cytoskeleton which plays an important role in generating oxygen radicals, its possible inhibition by ibuprofen could additionally explain the antiphlogistic effect of this compound. PMID- 8192701 TI - [Synthesis and antibacterial action of new ureido- and dicarboxylic acid diamido- derivatives of acylpenicillins with and without catechol substituents]. AB - New ureido, oxamoyl, fumaramoyl and terephthalamoyl derivatives of ampicillin or amoxicillin were synthesized by reaction of acylpenicillines with o-dihydroxy- or o-diacyloxy substituents containing aromatic amines bound over CO- or dicarboxylic groups. Corresponding compounds derived from 3,4-diacetoxyaniline showed significant increase of activity against pseudomonas and salmonella in contrast to derivatives without catechol substituents. No increase of activity was observed by corresponding derivatives of bi- and tricyclic amines. Derivatives with oxamoyl, fumaramoyl or terephthalamoyl groups were found to be more active than the corresponding ureido derivatives. Studies with mutants possessing higher membrane permeability have shown that the high activities of catechol containing derivatives are connected with the improved penetration through the outer membrane. Some new penicillin derivatives are more stable against beta-lactamases compared with azlocillin. PMID- 8192700 TI - Synthesis and aldose reductase inhibitory activity of 2-substituted-6-fluoro-2,3 dihydrospiro [4H-1-benzopyran-4, 4'-imidazolidine]-2',5'-diones. AB - Optically active and racemic 2-substituted-6-fluoro-2,3-dihydrospiro[4H-1 benzopyran-4, 4'-imidazolidine]-2',5'-diones were synthesized from (+)-, (-)-, and (+-)-6-fluoro-3,4-dihydro-4-oxo-2H-1-benzopyran-2-carboxylic acid. These compounds were then evaluated for in vitro and in vivo aldose reductase inhibitory activity. The 2S,4S isomers were found to be more potent aldose reductase inhibitors than the other corresponding stereoisomers. Among these compounds, (2S,4S)-6-fluoro-2,3-dihydro-2',5'-dioxospiro[4H-1-benzopyran-4, 4' imidazolidine]-2-carboxamide ((+)-1b, SNK-860, CAS 105300-43-4) showed the most potent in vitro and in vivo activity. PMID- 8192702 TI - Acute toxicity and effects on hepatic oxidative drug metabolism of mopyridone. AB - Mopyridone (CAS 82822-14-8) is a new chemotherapeutic with a strong antiviral effect (vs. influenza- and toga viruses) and certain advantages over the chemotherapeutics known so far. Toxicological studies reveal its low oral and intraperitoneal toxicity in mice and rats. The 5- and 14-day administration of mopyridone (37.5 mg/kg b.w., orally) to male rats established a growing tendency to the shortening of hexobarbital sleeping time, associated with moderate changes in the hepatic oxidase activity on the 15th day, most pronounced for amidopyrine N-demethylase (by 37%) and less for benzphetamine N-demethylase (by 17%). Aniline hydroxylase activity was slightly diminished (by 18% and 16%, resp.). No significant changes in the components of the electron-transport chain of cytochrome P-450 were established--the content of cytochrome P-450, cytochrome b 5 and cytochrome C reductase, both after 5- and 14-day mopyridone administration. PMID- 8192703 TI - Studies on the antiviral activity of propagermanium with immunostimulating action. AB - The effects of propagermanium (3-oxygermylpropionic acid polymer) on various virus-infected mice were investigated. Propagermanium did not inhibit the multiplication of various DNA or RNA viruses in vitro. Oral administration of propagermanium in mice infected with herpes simplex virus type I (HSV-1) significantly prolonged the mean survival days. The efficacy of propagermanium at doses of 1 and 10 mg/kg daily was 13.4 +/- 2.3 and 14.2 +/- 2.3 mean survival days in comparison with 7.7 +/- 0.5 mean survival days at control group. In vaccinia virus-infected mice, oral doses of propagermanium ranging from 0.2 to 10 mg/kg suppressed the number of pocks on the tail which induced by the virus. Propagermanium (0.5-10 mg/kg) orally given to HSV-1-infected mice induced cytotoxic T lymphocytes (CTL) against HSV-1 antigen. In addition, propagermanium (1-10 mg/kg) enhanced interferon-gamma (IFN-gamma) induction in mice treated with Mycobacterium bovis (BCG). In mice spleen cells cultured with Concanavalin A, 0.1 to 10 micrograms/ml of propagermanium stimulated interleukin 2 (IL-2) production. It seems likely that the antiviral activity of propagermanium was exerted via enhancement of host immune resistance against viral infection. PMID- 8192704 TI - [The effects of plant preparations on cellular functions in body defense]. AB - Two preparations of Echinacea purpurea and a preparation of Eleutherococcus senticosus increased the in vitro phagocytosis of Candida albicans by granulocytes and monocytes from healthy donors by 30-45%. The chemotactic migration of granulocytes in the Boyden Chamber was increased by 45% with an Echinacea purpurea extract. The two herbal preparations had no effect in either direction on intracellular killing of bacteria or yeasts. Echinacea and Eleutherococcus preparations did not induce in vitro transformation of lymphocytes. The mistel toe preparation examined (Viscum album) did not influence the tested functions of granulocytes, monocytes or lymphocytes of healthy donors. PMID- 8192705 TI - Indocyanine green pharmacokinetics in rats with progressive carbon tetrachloride induced hepatocellular insufficiency. AB - Indocyanine green (ICG, CAS 3599-32-4) kinetics were used to assess hepatic function in rats with progressive hepatic disease induced by carbon tetrachloride administered by two different routes (intragastric and intraperitoneal). Four groups of animals with hepatic insufficiency (4, 6, 8, 10 weeks of intoxication) and two control groups (with or without phenobarbital/oil) were studied. After an i.v. bolus (1 mg/kg) of ICG, blood samples were collected for 120 min at definite time. For the intragastric route, ICG clearance and volume of distribution at steady-state were significantly decreased (p < 0.05), area under the curve and terminal half-life were significantly increased (p < 0.05). By contrast, no significant difference was observed after intraperitoneal administration, although the same pathological pattern was observed between the two routes of administration. This study proved the clinical importance of drug pharmacokinetics knowledge in liver disease and confirmed that ICG disposition is an adequate method for assessing hepatic function and dysfunction in animals with progressive liver disease. PMID- 8192706 TI - Mast cell distribution in rats. AB - A survey on the distribution of mast cells in healthy rats was carried out. Mast cells were present in abundance in mesenteric lymph nodes and tongue and to a lesser extent in sciatic nerve. Fewer numbers of mast cells were seen in other lymph nodes, heart, salivary gland, thymus, pancreas, cervix, vagina, uterus, epididymis, liver, skeletal muscle, ovaries, prostate, seminal vesicles, harderian glands, parathyroid, thyroid, mammary gland, skin, adipose tissue, preputial gland, tail and bone marrow. Scattered individual mast cells were occasionally seen in submucosa and serosa of stomach, oesophagus, small and large intestine and urinary bladder. Mast cells were very rare in lung, spleen and adrenals. Mast cells were not seen in kidney, pituitary, testes, bone spinal cord, brain, optic nerves and eyes. In lymph nodes, mast cells appeared mainly in medullary sinusoids with varying extent. There was no clear evidence of a difference between numbers of mast cells in young and older animals. There was evidence of increased numbers of mast cells in inflammatory lesions, of skin and heart. Mast cells were seen associated with mammary tumours, fibromas and fibrosarcomas. There were more mast cells in rats than in mice. Mast cells appear to be more abundant in Wistar rats than in CD rats. Mast cells were hardly seen in healthy dogs and primates except a few in tongue and sciatic nerve. Presence of mast cells is incidental and not indicative of any abnormalities. PMID- 8192707 TI - Radioiodine therapy for thyrotoxicosis. PMID- 8192708 TI - Prevalence of substance abuse by seriously mentally ill patients in a partial hospital program. PMID- 8192709 TI - mtDNA in congenital myotonic dystrophy. PMID- 8192710 TI - Reconstruction of a cheek defect with a forehead flap in one stage. PMID- 8192711 TI - Varicella zoster virus infection in pregnancy. PMID- 8192712 TI - Hyperammonemia secondary to valproic acid as a cause of lethargy in a postictal patient. AB - Hyperammonemia has been described as a complication of valproic acid therapy but may often be overlooked as a cause of lethargy in the postictal patient who presents to the emergency department. We present the case of a postictal patient with lethargy, hyperammonemia, otherwise normal liver function tests, and a therapeutic valproic acid level. Based on our experience and on previously published data, serum ammonia levels appear to be indicated in all ED patients on valproic acid therapy who present with altered mental status. To the best of our knowledge, this has not been reported previously in the emergency medicine literature. PMID- 8192713 TI - Hepatitis C virus and cryoglobulinemia. PMID- 8192714 TI - Authors have rights too. AB - Without publication research can be of little value. When researchers approach publication there is ample published guidance for them on what their obligations are, and there are well known style guides within each scientific discipline including, in medicine, the Vancouver style. This article gives a series of anonymous examples to suggest that the impact of similar guides for editors has been patchy and to make some suggestions for better communication. PMID- 8192715 TI - Postmenopausal hormone replacement therapy. PMID- 8192716 TI - Physicians and abortion. PMID- 8192717 TI - Plagiarism. PMID- 8192718 TI - Detection and determination of interfering 5-hydroxymethylfurfural in the analysis of caramel-coloured pharmaceutical syrups. AB - A comparison between different caramels described for use in the pharmaceutical industry is presented. An interfering substance, 5-hydroxymethylfurfural (5-HMF), was detected in some caramels. Conditions and proofs for the formation of 5-HMF are presented. Interference by 5-HMF during the analysis of the active drugs and the possibility of interaction with the active drugs during the shelf-life of the drug formulation are discussed. A limit test for 5-HMF in caramel was developed. The test depends on measuring the difference in absorbance between two equimolar solutions of caramel, one of which contains sodium borohydride. The test is sensitive and selective for the detection and determination of trace amounts of 5 HMF without interference from the brown products of caramel. PMID- 8192719 TI - Prevention and treatment of Pneumocystis pneumonia. PMID- 8192720 TI - The effect of spinal manipulation on pain and prostaglandin levels in women with primary dysmenorrhea. PMID- 8192721 TI - Conflict of interest. The new McCarthyism in science. PMID- 8192722 TI - A psychodynamic model of panic disorder. AB - Current psychiatric research on panic disorder and its treatment are heavily influenced by neurobiological and cognitive-behavioral models rather than psychodynamic propositions, and psychodynamic treatment is generally considered to be of little benefit in amelioration of symptoms. However, because neither of the current models fully explains the clinical psychopathology, etiology, or pathogenesis of panic disorder, there is a need for further model building. The authors suggest that a psychodynamic approach may add to the understanding of patients with panic disorder. They base their psychodynamic formulation on pilot interviews with nine patients with panic disorder, published reports of psychological characteristics of patients with panic disorder, and data from infant and animal research on temperament. Interview results included the following: 1) all of the patients described themselves as fearful, nervous, or shy as children, 2) they remembered their parents as angry, frightening, critical, or controlling, 3) they frequently indicated discomfort with aggression, 4) most described chronic feelings of low self-esteem, 5) their spouses were characterized as passive, kind, and nonaggressive, and 6) stressors associated with frustration and resentment preceded the onset of panic. The authors propose a model in which inborn neurophysiological irritability predisposes to early fearfulness. Exposure to parental behaviors that augment fearfulness results in disturbances in object relations and persistence of conflicts between dependence and independence, which predispose to fears of feeling trapped, suffocated, and unable to escape and/or feeling alone and unable to get help. Catastrophic fears of helplessness in the face of suffocation or abandonment are easily accessible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192723 TI - Perioperative blood transfusion and outcome after resection for colorectal carcinoma. AB - The degree of immunomodulation by perioperative blood transfusion and its effect on oncological surgery remain controversial. A major problem with previous clinical studies has been the inadequate patient population in each and the presence of confounding variables. To resolve some of the controversy, all studies published between 1982 and 1990 were reviewed using the statistical method of Mantel-Haentszel-Peto to determine a cumulative estimate of the direction and magnitude of this association. Some 20 papers were included in the analysis, representing 5236 patients. The cumulative odds ratios (95 per cent confidence interval) of disease recurrence, death from cancer and death from any cause were 1.80 (1.30-2.51), 1.76 (1.15-2.66) and 1.63 (1.12-2.38) respectively. These results support the hypothesis that perioperative blood transfusion is associated with an increased risk of recurrence of colorectal carcinoma and death from this malignancy. PMID- 8192724 TI - Evaluating behavioral interventions: need for randomized controlled trials. PMID- 8192725 TI - Awake blind nasal intubation. PMID- 8192726 TI - Adolescent homosexuality: a primary care perspective. PMID- 8192727 TI - Hepatitis C virus antibody in patients with primary liver cancer (hepatocellular carcinoma, cholangiocarcinoma, and combined hepatocellular-cholangiocarcinoma) in Japan. AB - BACKGROUND: In hepatocellular carcinoma (HCC), a high prevalence of hepatitis C virus antibody (anti-HCV) has been reported, indicating that it may be an important etiologic factor in the pathogenesis of HCC. In this study, the authors investigated the prevalence of anti-HCV in HCC patients, as well as the same prevalence in patients with cholangiocarcinoma (CC) and combined hepatocellular cholangiocarcinoma (combined HCC-CC), to study the clinicopathologic features of anti-HCV-positive cases. METHODS: The authors examined 141 patients with primary liver cancer who were pathologically diagnosed as having HCC (121 cases), CC (13 cases), or combined HCC-CC (7 cases). Hepatitis B surface antigen (HBsAg) and anti-HCV were measured in these patients. RESULTS: Of 121 HCC cases, 85 (70.3%) were found to be anti-HCV positive, 16 (13.2%) were HBsAg positive, and 5 (4.1%) were both anti-HCV and HBsAg positive. In 13 cases with CC and in 7 with combined HCC-CC examined, 4 (30.8%) and 5 (71.4%), respectively, were anti-HCV positive. CONCLUSIONS: The anti-HCV-positive rate was high in combined HCC-CC as well as in HCC. These three types of primary liver cancer, which were anti-HCV positive, shared two common features: male dominance and high incidences of complication with liver cirrhosis. PMID- 8192728 TI - Can linoleic acid contribute to coronary artery disease? AB - The adipose tissue concentration of linoleic acid was positively associated with the degree of coronary artery disease (CAD) in a cross-sectional study of 226 patients undergoing coronary angiography. Linoleic acid concentration in adipose tissue is known to reflect the intake of this fatty acid. These results are therefore indicative of a positive relationship between linoleic acid intake and CAD. The platelet linoleic acid concentration was also positively associated with CAD. After confounding factors were allowed for, the eicosapentaenoic acid concentration in platelets was inversely associated with CAD for men, and the docosapentaenoic acid concentration in platelets was inversely associated with CAD for women; results consistent with several other studies that suggest that fish, and omega-3 fatty acids derived from fish and fish oils, can beneficially influence macrovascular disease. PMID- 8192729 TI - Pre-reconstruction tattooing eliminates the need for skin grafting in nipple areolar reconstruction. AB - Tattooing the skin of the reconstructed breast as a prelude to reconstruction of the nipple provides a nipple areolar reconstruction that has a uniform color. There is no requirement for a skin graft donor site. Tedious tattooing of the nipple papule is avoided. It is much easier to tattoo a flat surface than a projecting papule, and this technique gives a more uniform color. We believe that this approach to nipple areolar reconstruction provides a simpler, dependable technique. PMID- 8192730 TI - Premature rupture of the membranes: diagnostic and management strategies. AB - Premature rupture of the membranes is associated with considerable neonatal and maternal morbidity when it leads to premature birth. In most cases, this condition occurs at term, does not require medical intervention and has a benign course. Although few effective preventive measures are available, the family physician should screen pregnant patients for remediable risk factors, including smoking and certain vaginal infections, such as trichomoniasis. Diagnostic strategies include assessment of the amniotic fluid and laboratory tests to evaluate fetal and maternal welfare. Management options include expectant treatment, induction of labor or initiation of corticosteroids, antibiotics and/or tocolytics. These options must be carefully evaluated because of the morbidity associated with prematurity and the increased incidence of sepsis in prolonged rupture of the membranes. PMID- 8192731 TI - Race and birthweight in biracial infants. AB - OBJECTIVES: The purpose of the study was to determine the role of infant race as a determinant of the Black-White disparity in low birthweight (< 2500 g). METHODS: Univariate analysis and multivariate logistic regression were performed on Illinois vital records from 1982 and 1983 and on 1980 United States census income data. RESULTS: Fourteen percent of the infants born to Black mothers and White fathers were of low birthweight, compared with 9% of infants born to White mothers and Black fathers and 6% of a random sample of White infants. Both groups of biracial infants were more likely to have been born to unmarried mothers and to reside in very low-income (< $10,000 per year) census tracts than were White infants. When all confounding variables were entered into a logistic model, the adjusted odds ratio of low birthweight for biracial infants born to Black mothers and White fathers equaled 1.4. When biracial infants born to White mothers and Black fathers were compared with White infants, the adjusted odds ratio of low birthweight equaled 1.0. CONCLUSIONS: Paternal and consequent infant race does not affect the birthweight distribution of those born to White mothers and Black fathers. Unidentified factors closely related to maternal race underlie the Black White disparity in infant birthweight. PMID- 8192732 TI - The laryngeal mask airway. Its uses in anesthesiology. AB - The LMA is a useful airway device for most adult and pediatric patients. It is easy and atraumatic to insert, with minimal somatic and autonomic responses from the patient. It is a suitable alternative to the face mask and to tracheal intubation in a wide variety of clinical situations. In addition, the LMA facilitates blind and fiberoptic techniques of intubation, but its role in the emergency scenario has yet to be established. The preliminary experience gained with this device in Europe and Australasia suggests that it may also transform contemporary anesthetic practice in the United States. PMID- 8192733 TI - A reevaluation of the role of crystalloid preload in the prevention of hypotension associated with spinal anesthesia for elective cesarean section. AB - BACKGROUND: Hypotension after spinal anesthesia for cesarean section remains a common and serious complication despite the use of uterine displacement and volume preloading. The current study revaluated the role of crystalloid volume preloading in this context. METHODS: In a two-stage open sequential design, patients presenting for elective repeat cesarean section were allocated to receive either no preload or 20 ml/kg crystalloid administered over 15-20 min before spinal anesthesia. Hypotension was defined as a decrease in systolic pressure to less than 100 mmHg and to less than 80% of baseline value, and the study was designed to detect a 20% difference in the incidence of hypotension between the groups, with statistical significance at the 10% (alpha = 0.1) level, one-tailed. RESULTS: One hundred forty patients were studied. Hypotension occurred in 43 (55%, 95% CI 43.4-66.4) preloaded and 44 (71%, 95% CI 58-81.8) unpreloaded subjects, a difference in incidence of 16% (95% CI 0.04-31.6), which was statistically significant. There were no significant differences in the severity, timing, or duration of hypotension; the dose requirement for ephedrine; or the clinical and biochemical status of neonates between the groups. The only difference seen was a lower mean base excess (-3.4, SD 2.81 mM-1) in the neonates of hypotensive mothers compared to neonates of nonhypotensive mothers (-2.4, SD 1.99 mM-1). CONCLUSIONS: The study confirms that hypotension associated with spinal anesthesia for cesarean section cannot be eliminated by volume preloading in the supine wedged patient. The relatively small reduction in incidence of hypotension challenges our perception of the value of crystalloid preload. Though volume preload in the elective cesarean section is advocated, the requirement for a mandatory administration of a fixed volume before spinal anesthesia for urgent cases has been abandoned. PMID- 8192734 TI - [A 50-year-old man with metamorphopsia and optic nerve swelling]. AB - We report a 50-year-old male having metamorphopsia associated with retinal edema. He was well until one month prior to the present admission when he developed occipital headache and backache. Three weeks later, he noted a sudden onset of twisting of visual images. On admission, he was in no acute distress with well preserved general conditions. Only neurological abnormalities were bilateral papilledema, retinal edema and horizontal nystagmus with a rotatory component. Routine blood chemistries were unremarkable. The CSF contained 28 cells/cmm with 60% consisting of large atypical cells. Cranial CT scans revealed no mass, however, the magnified orbital CT showed bilateral swelling of the optic nerve. He was treated with ventriculoperitoneal shunt and Ommaya tube placement through which methotrexate, cytarabine and prednisolone were administered. He was also treated with systemic cisplatin, mitomycin-C and 5-fluorouracil. With these therapy, his headache, metamorphopsia and papilledema improved. He was discharged for out-patient follow-up, however, he had to admitted again because of progressive difficulty of gait and loss of appetite. On admission, he complained of severe backache, and his gait disturbance appeared to be in part due to his backache. A slight weakness was noted in all four limbs with loss of deep reflexes. Mentally he was alert and cranial nerves appeared intact without papilledema. But nuchal rigidity was noted. Cranial CT scan revealed attenuation of all the cortical sulci and marked diffuse low density changes in the cerebral white matter, and his chest film revealed a ring-shape shadow in his left lung field. He deteriorated progressively with terminal gastrointestinal hemorrhage. He expired three weeks after his second admission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192735 TI - The United States needs a health system like other countries. AB - Every developed country except the United States has a comprehensive health system for coverage, service provision, and finance. Social policy in the United States once was guided by thinkers who realized this, and the Social Security system--complete except for health insurance--resulted. The climate of thinking changed, and health policy for some time has been dominated by classical economists who argue that free competitive markets will solve all problems. They justify their arguments by claiming that the only alternative is full government takeovers of service and financing, as in Canada. While this debate has dragged along, problems in the United States have become grave. Instead of reviving the institutional economics and social policies that once served the United States well, the Clinton administration has turned policy over to devotees of managed competition. But the problem is how to organize the country, and national health insurance--easily observed in other countries--is superior to the current chaos and free-market utopias in the United States. Important aims would be achieved, such as expanding coverage, obtaining stable revenue, and containing costs. Important political barriers can be overcome, such as resistance by small business. Such a health system includes machinery for setting goals and implementing results, involving collaboration among providers, payers, and government. PMID- 8192736 TI - Congenital diaphragmatic hernia: influence of associated malformations on survival. AB - The medical records of 116 consecutive cases of congenital diaphragmatic hernia (CHD) among 368,772 live births at the three maternity hospitals in Dublin were examined and the incidence of associated malformations and their impact on survival analysed. The patients were divided into two groups: group I included 64 (55%) patients who died during resuscitation and stabilisation before surgery at a mean age of 11.2 hours and group II included 52 (45%) patients who were operated upon. All patients in group I underwent detailed postmortem examination as did the 45% patients who died in group II. The mean (SD) gestational age for group I patients (36.1 (4.5) weeks) was significantly lower than the mean gestational age of group II patients (39.0 (2.4) weeks). Similarly, the mean birth weight of group I patients (2415 (906) g) was significantly lower than that of group II patients (3140 (563) g). Of the newborns who died before surgery, 40 (62.5%) patients had 79 associated malformations. The major associated anomalies were: cardiac (n = 16), neural tube defects (n = 15), skeletal (n = 8), chromosomal (n = 5), urinary tract (n = 6), gastrointestinal (n = 3), omphalocele (n = 4), craniofacial (n = 5), pulmonary (n = 2), and syndromes (n = 2). Sixteen (40%) of these patients were found to have multiple anomalies. Of the 52 patients who were operated upon, only four (7.7%) had associated malformations. Our data shows that associated malformations in neonates with CDH is a major factor influencing outcome in this congenital malformation. PMID- 8192737 TI - Trapped by an incidental finding. PMID- 8192738 TI - Childhood abuse and neglect among women outpatients with chronic mental illness. AB - OBJECTIVE: The purposes of the study were to determine the prevalence of childhood sexual abuse, physical abuse, and neglect among women outpatients with severe and persistent mental illness; to examine patterns of co-occurrence of the various types of abuse; and to explore the relationships between childhood abuse and adult psychiatric symptomatology. METHODS: Childhood histories of abuse and data on clinical characteristics of 78 women enrolled in a New York State outpatient clinic were elicited in face-to-face interviews using a structured questionnaire. RESULTS: Sixty-five percent of the women reported histories of some type of abuse or neglect during childhood. Forty-five percent of the sample had been sexually abused, 51 percent had been physically abused, and 22 percent had experienced neglect. Seventy-four percent of the sexually abused women, 70 percent of the physically abused women, and 94 percent of the women who experienced neglect reported at least one additional form of abuse or neglect. Respondents who had been abused in childhood had higher levels of depressive and psychotic symptoms and higher rates of sexual victimization in adulthood than those who had not been abused. Women who experienced neglect as children had higher rates of homelessness in adulthood. CONCLUSIONS: Chronic mentally ill women seem to experience higher rates of abuse and more types of abuse than the general population. Clinicians should try to determine whether chronic mentally ill women have histories of abuse and to develop interventions to meet their special needs. PMID- 8192739 TI - How aggressive should delivery room cardiopulmonary resuscitation be for extremely low birth weight neonates? PMID- 8192740 TI - Brackets: plain, prescribed, preadjusted? PMID- 8192741 TI - Cimetidine reduces erythrocyte protoporphyrin in erythropoietic protoporphyria. PMID- 8192742 TI - Improving psychiatric services in managed care programs. PMID- 8192743 TI - Delayed perforation of the colon following colonoscopic biopsy. PMID- 8192744 TI - Supervision in the outpatient clinic: effects on teaching and patient care. AB - Two levels of faculty supervision in a resident teaching clinic were compared. Attending physicians recorded their impressions of diagnoses, treatment, severity of illness, and resident performance from case presentation alone and again after personally evaluating the patient. After direct evaluation, the attendings judged patients to be more seriously ill and rated resident performance lower. Changes in diagnosis and management were frequent. The attendings considered seeing the patient in person valuable for teaching in 18% of the cases, and for management in 27% of the cases. Faculty-patient interaction doubled supervisory time. Outpatient teaching and patient management are significantly affected when faculty see patients in person. PMID- 8192745 TI - Evaluation of three theophylline dosing equations for use in infants up to one year of age. AB - To develop appropriate theophylline dosage recommendations for infants < or = 1 year of age, we evaluated the Nassif, Hendeles, and Hatzopoulos dosing equations in 75 infants who were receiving theophylline intravenously by continuous infusion. Postnatal age ranged from 1 to 52 weeks and postconceptional age from 33 to 93.8 weeks. Using each patient's measured theophylline clearance at steady state and the dose recommended by each of the three equations, we predicted a steady-state serum theophylline concentration for the three equations. The recommended theophylline dose and resultant serum concentrations differed significantly for the three equations. The Nassif, Hendeles, and Hatzopoulos equations resulted in 78.7%, 97.3%, and 93.8%, respectively, of serum theophylline concentrations between 5 and 15 mg/L. The Hendeles and Hatzopoulos equations tended to produce concentrations between 5 and 10 mg/L in the majority of infants; the Nassif equation generally resulted in values between 10 and 20 mg/L. Four percent of the calculated serum concentrations with the Nassif equation were > 20 mg/L. When a desired concentration of 10 mg/L was used in the Hatzopoulos equation, predictions of theophylline concentrations were consistently inflated. We conclude that the Hendeles equation ((0.008 x Postnatal age in weeks) + 0.21 = mg/kg per hour or mg/kg daily = (0.2 x Postnatal age in weeks) + 5) is preferred when intravenous theophylline therapy for apnea and bradycardia or for asthma is initiated. Regardless of the equation used to estimate an initial theophylline dose in infants < or = 1 year of age, serum theophylline concentrations should be monitored within 6 to 12 hours after the start of therapy. PMID- 8192746 TI - Surgery in Japan. AB - Prominent progress has been made in the field of surgery in Japan following the examples of Germany and the United States before and after World War II, respectively. At present, surgery in japan seems to have reached almost top levels in the field of research as well as medical care. Although the educational system and medical training in the field of surgery in Japan have followed those methods of western countries, these methods are slightly modified at the present time. In this report, I give an overview of the current status of surgery in Japan, from the viewpoints of the postgraduate educational system, manpower, health care financing, and research development. I also refer to characteristics of surgery in Japan and recent topics. PMID- 8192747 TI - T cell lymphoid aggregates in bone marrow in idiopathic hypereosinophilic syndrome. AB - Idiopathic hypereosinophilic syndrome (HES) comprises a heterogeneous group of disorders characterised by prolonged eosinophilia with no obvious cause. A patient with longstanding HES is reported in whom unusual non-neoplastic peritrabecular lymphoid aggregates were present in the bone marrow, a hitherto undescribed association, as far as is known. An eosinophil colony stimulating activity was detected in the serum. The findings in this patient provide further evidence for an important role for eosinophil colony stimulating activity interleukin-5 mediated T lymphocyte control of eosinophil production in the pathogenesis of the HES. PMID- 8192748 TI - Privacy and security of personal information in a new health care system. PMID- 8192749 TI - Position of fine-bore nasogastric tubes. PMID- 8192750 TI - Seizures associated with poisoning and drug overdose. AB - A retrospective review of cases consulted by the San Francisco Bay Area Regional Poison Control Center during a 2-year period was performed to determine the causes and consequences of seizures associated with poisoning and drug intoxication. Of 233 charts coded as involving seizures, 191 occurred in humans and were available for analysis. The leading causes of seizures reported to the Poison Control Center were cyclic antidepressants (55 cases, 29%); cocaine and other stimulants (55 cases, 29%); diphenhydramine and other antihistamines (14 cases, 7%); theophylline (10 cases, 5%); and isoniazid (10 cases, 5%). Stimulants and diphenhydramine were more likely than other drugs to produce brief, self limited seizures. In contrast, poisoning by cyclic antidepressants, cardiodepressant antiarrhythmic agents, or theophylline was more likely to be associated with death. Seizures in elderly patients were more likely to result in complications and death. The frequency of seizure-related cases by substance type was also compared with the results of an earlier survey performed in 1981, and found a striking increase in the proportion of seizures caused by cocaine and (23% in 1988 to 1989 compared with 4% in 1981). Poison Control Center data can provide valuable information about the causes and consequences of drug-related medical complications, as well as highlight changing trends in drug-related injury. PMID- 8192751 TI - Clinical correlates of circulating immune complexes and antibody reactivity in squamous cell carcinoma of the head and neck. The Department of Veterans Affairs Laryngeal Cancer Study Group. AB - PURPOSE: To evaluate the correlation between the presence and titer of host derived antibody reactivity, circulating immune complexes, and clinical course and prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: Serum samples, obtained from untreated patients with squamous cell carcinoma of the larynx entered onto a multiinstitutional trial, were evaluated for the presence of elevated circulating immune complexes (221 patients) and host-derived antibody directed against two SCCHN cell lines (107 patients). RESULTS: Patients had significantly elevated levels of circulating immune complexes as measured by C1q binding compared with normal controls. Patients with higher levels of circulating immune complexes were less likely to respond to chemotherapy. No correlations were noted between immune complex levels and stage of disease, nodal status, site of disease, recurrence, or survival. Evaluation of native antibody titers for their relationship to clinical correlates showed no statistically significant associations. In sera subjected to immune complex dissociation, patients with moderately or poorly differentiated tumors had significantly higher antibody titers when compared with patients with well-differentiated tumors. Because marked variation in the increase of antibody titers following immune complex dissociation was noted, the ratio of immune complex-dissociated to native antibody titer was examined. Patients with a high ratio had a lower proportion of complete and partial responses to chemotherapy. CONCLUSION: Our results support the conclusion that the formation of tumor-associated immune complexes in patients with SCCHN is associated with a decreased response to chemotherapy. PMID- 8192752 TI - Human situs determination and chromosome constitution 46,XY,ins(7;8)(q22;q12q24) PMID- 8192753 TI - Cystic fibrosis identified by neonatal screening: incidence, genotype, and early natural history. PMID- 8192754 TI - Advanced-practice nursing--good medicine for physicians? PMID- 8192755 TI - Health care abuse. PMID- 8192756 TI - Management of extensive facial basal cell carcinoma by excision and microvascular tissue transfer. AB - Management of large or recurrent basal cell carcinomas (BCCs) on the face can be difficult, especially where radiotherapy has been the primary treatment. Free tissue transfer using microvascular surgery permits wide excision margins ensuring clearance of the tumour without being compromised by concern over closure, since the free flap can be designed after the excision of the tumour and its size and composition can thus be custom made. Age alone should not be a contraindication to this major procedure. PMID- 8192757 TI - Myths: endocarditis. PMID- 8192758 TI - Expanded roles for NPs and PAs? PMID- 8192759 TI - Antimicrobial therapy of acute otitis media. PMID- 8192761 TI - The overdiagnosis of Lyme disease. PMID- 8192760 TI - Debate on using adjuvant chemotherapy. PMID- 8192762 TI - Imaging for sinusitis. PMID- 8192763 TI - Incisions for removing and/or replacing silicone gel breast implants. PMID- 8192764 TI - Morphine for dyspnea in patients with cancer. PMID- 8192765 TI - [A 75-year-old man with parkinsonism and delirium]. AB - We report a 75-year-old man with a ten-year history of parkinsonism, who developed acute delirium. He was well until 65 years of age, when there was an onset of tremor in his left hand. He had been treated with levodopa and trihexyphenidyl with marked improvement. He was doing well until July of 1991 at his age of 75-year-old, when he noted backache; he was found to have a compression fracture of the third lumbar spine. He had to use a wheel-chair most of the time since then. In December 1991, he started to have visual hallucinations and difficulty in swallowing. On December 25 of that year, he developed fever and delirium, and was admitted to our hospital on December 30. On admission, general physical examination was unremarkable except for low grade fever (37.3 degrees C). Neurologic examination revealed an alert but chronically ill patient. Apparently he had visual hallucinations. He was disoriented to all spheres; he could respond only to simple questions. Apparently he was demented. Cranial nerves were intact except for mumbling speech disturbance and masked face. He was unable to stand or walk. He had flexion contracture in his both knee joints. He had paratonic rigidity in all his limbs and marked bradykinesia. Once in a while, myoclonic jerks were seen in both upper and lower extremities. Deep reflexes were diminished bilaterally, and the plantar reflex was not elicited on either side. On laboratory examination, BUN was increased to 72 mg/dl, creatinine to 3.0 mg/dl, and WBC 16,000/microliter. Cranial CT scans were unremarkable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192766 TI - Intravenous fluid preload in the prevention of spinal block-induced hypotension in parturients. PMID- 8192767 TI - Substance abuse among anesthesiologists. PMID- 8192768 TI - Linoleic acid and coronary artery disease. PMID- 8192769 TI - Cardiorespiratory arrest following combined spinal epidural anaesthesia. PMID- 8192770 TI - Invasive or allergic fungal sinusitis? PMID- 8192771 TI - Don't shoot the messenger. PMID- 8192772 TI - Silent ischemia in unstable angina: altered cardiac norepinephrine handling. PMID- 8192773 TI - Focal and diffuse visual field defects related to intraocular pressure. PMID- 8192774 TI - Thoughts about premature rupture of the membranes. PMID- 8192775 TI - Anophthalmic socket pain. PMID- 8192776 TI - Prospective surveillance of neonatal meningitis. PMID- 8192777 TI - Posterior retinal folds following vitreoretinal surgery. PMID- 8192778 TI - Conscious levels during anaesthesia. PMID- 8192779 TI - Perioperative blood transfusion and outcome after resection for colorectal carcinoma. PMID- 8192780 TI - Neonatal effects of maternal epidurals. PMID- 8192781 TI - Slow release aspirin in the elderly. PMID- 8192783 TI - Pharmaceutical care and inpatient outcomes. PMID- 8192784 TI - Hereditary nodular heterotopia accompanied by mega cisterna magna. PMID- 8192782 TI - Reply to: retracted confessions: through opiate withdrawal to a new conceptual framework. PMID- 8192785 TI - Anaesthetists and euthanasia: another perspective. PMID- 8192786 TI - Response to spinal anesthesia after inadequate epidural anesthesia. PMID- 8192787 TI - Erythromelalgia versus primary and secondary erythermalgia. PMID- 8192788 TI - Bladder tumours among U.K. rubber workers. PMID- 8192790 TI - 'Inflammation or sepsis' is not the actual question in reactive arthritis. PMID- 8192789 TI - Anticentromere autoantibodies and Sicca syndrome. PMID- 8192791 TI - Diabetes mellitus due to viruses--some recent developments. PMID- 8192793 TI - Minor papilla sphincterotomy in pancreas divisum. PMID- 8192794 TI - Resident supervision in outpatient clinics. PMID- 8192792 TI - Enteroscopy for unexplained iron-deficiency anemia: take enough biopsies. PMID- 8192795 TI - Thrombotic thrombocytopenic purpura in systemic lupus erythematosus. Italian Cooperative Group for TTP. PMID- 8192797 TI - Advanced-practice nursing--good medicine for physicians? PMID- 8192796 TI - Regarding "Creation of a distal arteriovenous fistula improves microcirculatory hemodynamics of prosthetic graft bypass in secondary limb salvage procedures". PMID- 8192798 TI - Antiepileptic drug myopathy. PMID- 8192799 TI - Bell's palsy. PMID- 8192800 TI - War souvenirs. PMID- 8192801 TI - Helical vs spiral. PMID- 8192802 TI - CT-guided biopsy: reducing the margin of error. PMID- 8192803 TI - Action on AIDS. PMID- 8192804 TI - Transvaginal ultrasonographic findings in surgically verified ectopic pregnancy. PMID- 8192805 TI - Laparoscopic hysterectomy: it is not such an expensive surgical procedure. PMID- 8192806 TI - Self-induced dysphoria and neural correlates. PMID- 8192807 TI - Insight in psychosis: state or trait? PMID- 8192808 TI - The mystery of antiphospholipid antibodies in Sneddon's syndrome. PMID- 8192809 TI - Occupational medicine--let's keep our white coats and stethoscopes. PMID- 8192810 TI - Health care abuse. PMID- 8192811 TI - Discordance between tuberculin skin test results with two commercial purified protein derivative preparations. PMID- 8192812 TI - Encephalopathy from abuse of bismuth subsalicylate (Pepto-Bismol) PMID- 8192813 TI - Prophylactic ZDV dosing frequency in macaques. PMID- 8192815 TI - The United States needs a health system like other countries. PMID- 8192814 TI - Variations in recommendations of ethics consultants. PMID- 8192816 TI - HIV-1 infection of non-dividing cells. PMID- 8192817 TI - Re: "Toward a clearer definition of confounding". PMID- 8192818 TI - Essential thrombocythemia and pregnancy. PMID- 8192819 TI - Hirulog therapy for heparin-associated thrombocytopenia and deep venous thrombosis. PMID- 8192820 TI - The reporting efficiency of measles by hospitals in Los Angeles County, 1986 and 1989. PMID- 8192821 TI - Portal vein versus hepatic artery chemotherapy. PMID- 8192822 TI - Slit mesh for hernia repair. PMID- 8192823 TI - Age-related changes in the neurologic examination of healthy sexagenarians, octogenarians, and centenarians. AB - Although numerous studies have focused on age-related changes in the nervous system, few have systematically assessed global neurologic examination changes, and even fewer have included the most elderly population, ie, the centenarians. To perform such a study, we developed a quantitative assessment that includes the major components of a standard bedside neurologic evaluation, with special emphasis on cognitive function. First, we demonstrated that the quantitated examination could correctly classify healthy controls and patients with stroke or dementia based on discriminant analysis. This examination was then applied to healthy community-dwelling elderly ranging from 60 to 108 years of age. Significant age-related neurobehavioral changes were apparent across even these most "successfully" aged groups. Analysis of the full pattern of cognitive and neurologic findings provided the most accurate assessment. Pathologic reflexes, reportedly associated with normal aging, occurred infrequently in this healthy geriatric population, suggesting that age-related changes in the neurologic examination may be more accurately interpreted when assessed in conjunction with cognitive status. This quantitative examination may be useful in future population-based studies of neurologic function in the aged. PMID- 8192824 TI - Bicaudate index on magnetic resonance imaging: effects of normal aging. AB - The bicaudate and bifrontal indices have been used in prior computed tomographic studies to investigate atrophy of the caudate nuclei in patients with Huntington's chorea and cerebral atrophy. However, the relationship between these indices and caudate volume has not been documented previously. In this study, we used high-field magnetic resonance imaging (MRI) to determine the effects of normal aging on the bicaudate and bifrontal indices and to study the relationship between these indices and caudate volume. The subjects were 49 normal volunteers, aged 22 to 82 years, who were without any significant neurologic or psychiatric disorders. Age was positively correlated with bicaudate index (r = .59; P < .0001) and bifrontal index (r = .40; P < .0047). Age was negatively correlated with caudate nuclei volume (r = -.47; P < .0005). Caudate volume was negatively correlated with bicaudate (r = -.27; P < .06) and bifrontal (r = -.31; P < .03) indices. These findings are consistent with prior reports of caudate nuclei degeneration with increasing age. Linear and volumetric caudate measurements with MRI may prove useful in the investigation of caudate nuclei function in the neuromotor decline with normal aging and in disorders such as Huntington's chorea. PMID- 8192825 TI - Acquired dementia with retinitis pigmentosa. AB - The coexistence of mental retardation and retinitis pigmentosa has been well described in a number of congenital syndromes such as the Lawrence-Moon and Bardet-Biedl disorders. In contrast to this, little information is available regarding the association of acquired dementia with retinitis pigmentosa. This report summarizes the clinical features of a developmentally normal adult having the unusual symptom complex of retinitis pigmentosa, early-onset dementia, sensorineural hearing loss, and sensorimotor neuropathy. Though the coexistence of retinitis pigmentosa and dementia in this particular patient may be completely coincidental, it could be representative of a previously unrecognized subset of dementing illness. The literature pertaining to related symptom complexes is reviewed and discussed. PMID- 8192826 TI - Hypothyroidism: does treatment cure dementia? AB - Demented individuals are traditionally investigated for potentially reversible causes. Hypothyroidism is generally accepted as being a condition that, if identified and treated, may be associated with improvement in mental state. A literature search was carried out to determine if data exist to show that this is so. Analysis of 2781 cases from studies of etiology in dementia revealed only one case of reversible dementia due to hypothyroidism. Problems associated with interpretation of previous reports include lack of acceptable criteria for diagnosis of dementia and inadequate follow-up. A randomized controlled trial will be needed to resolve this issue. PMID- 8192827 TI - A new Italian pedigree with early-onset Alzheimer's disease. AB - We have recently discovered in Torino (Italy) a new pedigree with early-onset Alzheimer's disease. The index patient is a woman who, at the age of 43 years, showed progressive memory impairment and ideomotor apraxia. Several relatives of the patient have had a history of dementia. The ancestors of the patient were from Calabria (southern Italy) and members of the family emigrated to the north of Italy, to France, and to the United States. Up to now, the new kindred comprises 1950 members, distributed in eight generations. Thirty members affected with Alzheimer's disease have been identified. Neuropathologic confirmation of antemortem clinically diagnosed Alzheimer's disease has been achieved for one patient. The pedigree is consistent with autosomal dominant inheritance. The clinical course of the disease is fairly uniform: the first symptom is memory loss, beginning around age 40 years. Psychiatric symptoms like hallucinations and delusions follow. At a later stage of the disease, several patients developed myoclonus and generalized epileptic seizures and eventually died with profound dementia. The "Torino family" shows several genealogic and clinical similarities with other large multigenerational familial Alzheimer's disease pedigrees originating from the Calabria region. PMID- 8192828 TI - Reliability and validity of the Short Portable Mental Status Questionnaire administered by telephone. AB - Effective, economical, and reliable means of screening subjects for cognitive impairment when personal contact is not feasible could facilitate epidemiologic studies and longitudinal assessment. The Short Portable Mental Status Questionnaire (SPMSQ) is a 10-item examination that has been found reliable and valid in distinguishing demented subjects from cognitively intact subjects when given face to face. The current study assessed the utility of a telephone version of the SPMSQ in patients evaluated in an outpatient geriatric assessment program. Mean scores for both test versions decreased with dementia severity and correlated significantly. Mean score differences between the two versions were not affected by reports of hearing impairment or the time interval between test administration. Both test versions correlated significantly with the Mini-Mental State Examination. In distinguishing demented from nondemented subjects, sensitivity and specificity were .74 and .79 for the telephone test and .74 and .91 for the face-to-face test, respectively. PMID- 8192829 TI - Comparative study of cerebral ventricular dilation and cognitive function in patients with Alzheimer's disease of early versus late onset. AB - The clinical, psychological, and neurologic characteristics of 37 Japanese patients with early-onset Alzheimer's disease (eAD; onset before age 65 years) were compared with those of 23 patients with late-onset Alzheimer's disease (lAD; onset at age 65 years or later). This study evaluated brain atrophy using computed tomographic (CT) scans, and the behavioral and psychological differences in the two groups using the Gottfries-Brane-Steen scale, Japanese revision (GBSS JR). Follow-up CT scans were obtained and compared in 20 patients with eAD, 24 patients with lAD, and 23 elderly nondemented control subjects. The size of lateral cerebral ventricular dilation, measured every 6 months following admission, was significantly larger in the eAD patients than in the control subjects. The characteristics of the 37 patients with eAD were compared with those of the 23 patients with lAD by evaluating the scores on all 38 items in the five categories of the GBSS-JR. To compare the test results by duration of disease, patients were divided into subgroups according to average duration of disease: eAD1 (nine patients), 2.2 years; eAD2 (16 patients), 5.0 years; eAD3 (12 patients), 9.0 years; lAD1 (seven patients), 1.6 years; lAD2 (10 patients), 3.1 years; and lAD3 (six patients), 5.3 years. The GBSS-JR scores were compared in duration-matched pairs, that is, eAD1 versus lAD1 and eAD2 versus lAD3. The eAD1 patients showed significantly worse scores in four categories and 13 items compared with the lAD1 patients. Fewer differences in scores were found between eAD2 patients and the lAD3 patients than between the eAD1 patients and the lAD1 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192830 TI - Cognitive Performance Test: a new approach to functional assessment in Alzheimer's disease. AB - A new performance-based assessment instrument for evaluating function in patients with Alzheimer's disease (AD), the Cognitive Performance Test (CPT), is described. This instrument, based on Allen Cognitive Disability Theory, uses six common activities of daily living (ADL) tasks, for which the information processing requirements can be systematically varied to assess ordinal levels of functional capacity. Seventy-seven patients with mild to moderate Alzheimer's disease (AD) and 15 neurologically normal elderly controls were administered the CPT. Subsets of the AD patients were assessed again at 4 weeks and 1, 2, and 3 years following the initial evaluation. Internal consistency of the CPT estimated by alpha was .84. Intraclass correlation for interrater reliability was .91 and for test-retest reliability at 4 weeks, .89. CPT scores were significantly correlated with Mini-Mental State Examination scores (r = .67) and two measures of caregiver-rated ADL (Instrumental Activities of Daily Living, r = .64; Physical Self-Maintenance Scale, r = .49). Significant declines in CPT scores were seen on 1-, 2-, and 3-year follow-ups. Initial CPT scores predicted risk of institutionalization over a 4-year follow-up period. PMID- 8192831 TI - Valproate in the treatment of posttraumatic bipolar disorder in a psychogeriatric patient. AB - The authors present an 83-year-old man who had developed posttraumatic bipolar disorder 22 years earlier. His condition was characterized by recurrent manic and depressive attacks. Valproate was found effective in controlling his symptoms. PMID- 8192832 TI - Memory self-report in Alzheimer's disease and in age-associated memory impairment. AB - We investigated memory self-report in Alzheimer's disease (AD) and age-associated memory impairment (AAMI). AD and AAMI patients and healthy elderly subjects were administered a self-report memory questionnaire, memory tests, a family-rated memory questionnaire, and a depression scale. The AD group reported worse memory than the control group, but many individual AD subjects reported normal memory. This finding confirms clinical observations that unawareness of memory loss is common in AD but variable across patients. Multiple regression analysis revealed that worse memory self-ratings were associated with greater dementia severity and higher depression scores. In the AAMI group, memory self-ratings were predicted by family ratings of memory ability but not by memory test scores. There was a nonsignificant trend for depression scores to predict memory self-ratings. Finally, level of self-reported memory ability did not differ for AD and AAMI, contradicting clinical lore that memory complaint is a useful diagnostic indicator. PMID- 8192833 TI - A case of organic mania associated with open heart surgery. AB - Organic mania has been reported to have multiple etiologies. A case is described of a patient who developed mania following a coronary artery bypass graft and mitral valve replacement. Cerebral abnormalities were not detected by computed tomographic or magnetic resonance imaging scans, but an area of dysfunction was found using single photon emission computed tomographic (SPECT) imaging. The lesion resolved when the patient became clinically asymptomatic. The area of decreased cerebral perfusion associated with the patient's mania was in an atypical location, raising questions about which brain regions can result in well defined psychiatric syndromes. PMID- 8192834 TI - T-maze spontaneous alternation rate is decreased in S100 beta transgenic mice. AB - S100 beta, a calcium-binding brain specific protein, may affect both brain development and hippocampal long-term potentiation. S100 beta levels are elevated in Down syndrome (DS), and the gene for S100 beta is located on chromosome 21, which is duplicated in DS. To test the hypothesis that, elevated levels of S100 beta cause behavioral alterations in a mammalian system, 3 transgenic mouse lines with multiple copies of the human gene for S100 beta were derived and behaviorally tested. The spontaneous alteration behavior of transgenic and normal littermate mice were compared in a T maze during a 15-trial test. The overall alteration rate was found to be significantly decreased in the transgenic mice compared with their normal littermates. The S100 beta transgenic mouse model offers one of the first opportunities to investigate the relation between overexpression of a human chromosome 21 gene product and abnormal behavior and brain function. PMID- 8192835 TI - Effects of chronic and acute cocaine treatment on the onset of maternal behavior and aggression in Sprague-Dawley rats. AB - Pregnant rats were treated either throughout gestation (GD 1-20) with 30 mg/kg per day (chronic cocaine) or with one 15-mg/kg dose immediately following parturition (acute cocaine). Chronic and acute cocaine treatment delayed or diminished the postpartum onset of some components of maternal behavior, and chronically treated dams were significantly more aggressive toward a male intruder than acute cocaine-treated or saline-treated dams. Cocaine increased the latency to crouch over pups and decreased crouch duration during a 30-min observation period that immediately followed parturition. Latencies to nest build were also longer in more chronic cocaine-treated dams than in saline controls. On Day 6 postpartum, 83% of chronic cocaine-treated dams pinned and attacked an intruder male 8 or more times during a 10-min observation period, whereas only 4% of acute cocaine-treated and none of the saline-treated dams exhibited this much aggression. PMID- 8192836 TI - Rhinal cortex lesions and object recognition in rats. AB - Rats with bilateral lesions of lateral entorhinal cortex and perirhinal cortex were tested on a nonrecurring-items delayed nonmatching-to-sample (DNMS) task resembling the one that is commonly used to study object recognition in monkeys. The rats were tested at retention delays of 4 s, 15 s, 60 s, 120 s, and 600 s before and after surgery. After surgery, they displayed a delay-dependent deficit: They performed normally at the 4-s delay but were impaired at delays of 15 s or longer. The addition of bilateral amygdala lesions did not increase their DNMS deficits. The present finding of a severe DNMS deficit following rhinal cortex damage is consistent with the authors' previous finding that bilateral lesions of the hippocampus and amygdala cause only mild DNMS deficits in rats unless there is also damage to rhinal cortex (D.G. Mumby, E.R. Wood, & J.P.J. Pinel, 1992). These findings add to accumulating evidence that the rhinal cortex, but not the amygdala, plays a critical role in object recognition. PMID- 8192837 TI - Differential expression of Fos protein in the brain of female mice dependent on pup sensory cues and maternal experience. AB - Immunoreactivity for Fos protein following 30 min of sensory and behavioral experience with foster pups was measured in different brain areas of nulliparous female Balb/c mice who were intact, ovariectomized, or selectively depleted of olfactory bulb noradrenaline. Fos expression was also investigated in intact nulliparous female mice undergoing distal exposure to pup sensory cues. Behavioral interaction with pups increased Fos immunoreactivity in the olfactory areas (anterior olfactory nucleus, piriform cortex, corticomedial amygdala, and entorhinal cortex) as well as in the medial preoptic area, and this occurred regardless of whether females were intact or ovariectomized. Noradrenaline depletion of the olfactory bulb prevented Fos induction in primary olfactory areas, but not in the medial preoptic area, whereas distal exposure to pup cues enhanced Fos expression in the olfactory areas but not in the medial preoptic area. PMID- 8192838 TI - Chlordiazepoxide microinjected into the region of the dorsal raphe nucleus eliminates the interference with escape responding produced by inescapable shock whether administered before inescapable shock or escape testing. AB - Systemic administration of benzodiazepines before exposure to inescapable shock (IS) blocks the enhanced fear conditioning and escape learning deficits that follow exposure to IS, whereas administration before the subsequent behavioral testing eliminates the enhanced fear but not the interference with escape. The failure of benzodiazepines to reduce the IS-produced escape learning deficit when given before testing is inconsistent with a recent proposal that interference with escape is mediated by an IS-induced sensitization of dorsal raphe nucleus (DRN) activity. The present experiments demonstrate that chlordiazepoxide will block both the enhancement of fear and interference with escape responding when given before either IS or testing if microinjected in the region of the DRN. This suggests that systemic benzodiazepines fail to block escape deficits when given before testing because action at a site distant from the DRN counters the effect of the drug at the DRN. PMID- 8192839 TI - Combined, but not single, gustatory nerve transection substantially alters taste guided licking behavior to quinine in rats. AB - On the basis of electrophysiological studies, the glossopharyngeal nerve (GL) is far more responsive to quinine than the chorda tympani (CT) or greater superficial petrosal (GSP) nerves. The licking behavior of water-deprived rats to quinine (0.03-3.0 mM) and distilled water (10-s trails) was tested before and after various nerve transections. GL+CT section caused a substantial reduction in responsiveness. GSP+CT section had a moderate effect, and GL section alone produced only marginal impairments. Control, partially desalivated, and CT sectioned rats were unaffected. Thus, the GL is not necessary for normal unconditioned taste-guided appetitive responsiveness to quinine, but the collective input from the GSP and CT is necessary and most likely sufficient. These data suggest that the quinine-evoked input of the GL and CT converge centrally. PMID- 8192840 TI - Inhibitory effects of estrogen on stimulated salt appetite in rats. AB - Adult male rats consumed 50-150% more 0.5 M NaCl solution than females did during a 7-hr drinking test when robust salt appetite was elicited by dietary sodium deprivation for 8 days, daily injections of deoxycorticosterone, or adrenalectomy followed by 2 days of sodium deprivation. In contrast, male rats drank much less saline after systemic treatment with the natriuretic agent furosemide, adrenalectomy followed by 1 day of sodium deprivation, or sc treatment with colloid solution after 2 days of sodium deprivation, and female rats drank comparably small volumes. Conversely, 30-day-old prepubescent male and female rats showed equally robust salt appetites after 8 days of sodium deprivation. These and other findings support an inhibitory role of estrogen on salt appetite in rats, which appears to occur only when the appetite is especially pronounced. PMID- 8192841 TI - Saturation of subjective reward magnitude as a function of current and pulse frequency. AB - In rats with electrodes in the medial forebrain bundle, the upper portion of the function relating the experienced magnitude of the reward to pulse frequency was determined at currents ranging from 100 to 1,000 microA. The pulse frequency required to produce an asymptotic level of reward was inversely proportional to current except at the lowest currents and highest pulse frequencies. At a given current, the subjective reward magnitude functions decelerated to an asymptote over an interval in which the pulse frequency doubled or tripled. The asymptotic level of reward was approximately constant for currents between 200 and 1,000 microA but declined substantially at currents at or below 100 microA and pulse frequencies at or above 250 to 400 pulses per second. The results are consistent with the hypothesis that the magnitude of the experienced reward depends only on the number of action potentials generated by the train of pulses in the bundle of reward-relevant axons. PMID- 8192842 TI - Learned changes in the rate of respiratory pumping in Aplysia fasciata in response to increases and decreases in seawater concentration. AB - In Aplysia fasciata, the sea hare, shock paired with moderate increases or decreases in the seawater concentration leads to pairing-specific increases in the respiratory pump rate in response to the same solutions an hour later. A common neural circuit underlies learned changes to increased and decreased seawater concentration, as shown by complete generalization of learning between these stimuli. Different neural circuitry controls learning after pairing a shock with pH 7 seawater, as shown by a lack of generalization of learning to this stimulus. Preexposure to strong changes in the seawater leads to sensitization of respiratory pumping. The hypothesis was tested that associative learning and sensitization arise from activation of common pathways. However, patterns of generalization of sensitization elicited by preexposure to altered seawaters differ from those produced by associative learning. PMID- 8192843 TI - Hypoalgesia in response to sensitization during acute noise stress. AB - Three experiments examined the antinociceptive response shown by rats during exposure to loud noise. Noise exposure resulted in a time-dependent elevation of radiant heat tail flick latency that varied as a function of stimulus intensity. Noise stress hypoalgesia in response to a 90-dB stimulus was blocked by pretreatment with the opioid antagonist naltrexone (0.1-7.0 mg/kg). Systemic administration of midazolam (2 mg/kg) prior to exposure to the stressor attenuated the elevation in tail flick latency. Because topographically similar antinociceptive responses may be elicited with a low intensity noise stimulus that has served as a Pavlovian conditional stimulus for shock, the use of this paradigm may permit direct comparisons of associative and nonassociative fear responses using qualitatively similar auditory stimuli. PMID- 8192844 TI - Genetic determinants of sensitivity to ethanol in inbred mice. AB - Mice from 15 inbred strains differed in sensitivity to ethanol-induced effects on open-field activity, hypothermia, rotarod ataxia, and anesthesia. Sensitivities to the different behavioral responses were generally uncorrelated. This suggests that the genetic determinants of behavioral sensitivity to one domain of ethanol effects are unrelated to those determining other responses. On the other hand, some variables were genetically related. For example, those strains sensitive to the loss of righting reflex induced by higher doses of ethanol showed reduced activity in the open field at lower doses and were more sensitive to ethanol induced decreases in rearing. More generally, the pattern of results suggests that genetically influenced sensitivity to ethanol is not a monolithic phenomenon. Rather, it is specific to the particular response variable studied. PMID- 8192845 TI - NMDA processes mediate anterograde amnesia of contextual fear conditioning induced by hippocampal damage: immunization against amnesia by context preexposure. AB - Hippocampal lesions in rats produce both a retrograde and an anterograde amnesia of contextual fear conditioning. The present experiments examined the anterograde deficit in context conditioning. The deficit produced by electrolytic hippocampal lesions was apparent when training occurred on 7, 14, or 28 days following surgery, confirming the durability of the amnesia. The role of the hippocampus in context conditioning may be related to an NMDA (N-methyl-D-aspartate) receptor mediated process. Both NMDA hippocampal lesions and intrahippocampal administration of an NMDA antagonist produced anterograde amnesia. Animals preexposed to the conditioning context 28 days prior to hippocampal lesioning were protected from the deficit normally produced by the lesions. Thus, the hippocampus must form a contextual representation during preexposure that is subsequently stored elsewhere. Once formed this representation of the context can be associated with an unconditional stimulus. PMID- 8192846 TI - Free-field binaural unmasking in ferrets. AB - Free-field detection by normal and monaural ferrets of a 500-Hz tone presented over 1 laterally placed loudspeaker and partially masked by narrow-band noise from 2 sources was studied at 2 angular separations of the noise sources (0 degree and 180 degrees). Monaural listening was achieved either by plugging 1 ear canal or removing 1 cochlea. Normal ferrets showed an improvement in detectability of the tone when there was a 180 degrees separation between the noise sources. This unmasking of the tone was abolished in both groups of monaural ferrets, suggesting that the unmasking was due to binaural processing. The development of an animal model demonstrating free-field binaural unmasking, in a species other than humans, will allow investigation into the functional consequences of experimental hearing loss. PMID- 8192847 TI - Landmark discrimination in the rat: a measure of allocentric spatial ability. AB - A landmark discrimination task similar to that previously used with monkeys was adapted to measure allocentric spatial ability in rats. Rats were trained to approach one of two food wells, placed 36 cm apart, based on the proximity of the landmark. During initial training, the landmark was adjacent to the baited food well (0 cm). As training progressed, the distance of the landmark from the baited food well was increased in 1.25-cm increments. Results show that rats were able to successfully use a landmark as an external referent up to a distance of 11 cm (when the midpoint between food wells was 18 cm). Following the stepwise training phase, a 64-trial test of mixed distances was administered, and performance was above 80% up to and including 12.5 cm from the near landmark. The results suggest that this landmark discrimination task provides a means to assess allocentric spatial ability in rats and to explore underlying neural mechanisms across species. PMID- 8192848 TI - Effect of an ascending dose regimen on the development of tolerance to the anticonvulsant effect of diazepam. AB - The effect of an ascending dose regimen on the development of tolerance to diazepam's anticonvulsant effect was assessed. During the 22 trials of the tolerance development phase, amygdala-kindled rats received either a series of dosage injections ranging from high (10 mg/kg), to low (1.0 mg/kg), and ascending (1.0 mg/kg and increased by 0.2-mg/kg increments to 3.0 mg/kg) or saline injections. Diazepam was administered by ip injection once every 48 hr, and each injection was followed 1 hr later by a convulsive stimulation. The ascending dose rats displayed significantly more tolerance to the anticonvulsant effect of diazepam than did the high dose, low dose, or saline rats. By contrast, both the ascending and high dose rats displayed a significant withdrawal effect (i.e., increased duration of convulsions) after the cessation of diazepam injections. Results demonstrate that administration of ascending dosages can facilitate the development of tolerance to anticonvulsant drug effects and that tolerance and withdrawal are not necessarily inextricably related. PMID- 8192849 TI - Declarative memory following anterior temporal lobectomy in humans. AB - This study hypothesized that verbal memory decline following anterior temporal lobectomy (ATL) is associated with a lack of significant neuropathology in resected left, but not right, hippocampus and is limited to measures of episodic memory only. Tests of immediate (digit span), semantic (visual naming), and episodic memory as measured by the California Verbal Learning Test (CVLT) were administered before and 6 months after resection of the anterior left (n = 36) or right (n = 26) temporal lobe. There were no effects of hippocampal pathology on measures of immediate or semantic memory for either ATL group or for episodic memory for the right ATL group. Left ATL patients who demonstrated no/mild hippocampal sclerosis exhibited significantly greater postoperative decline in episodic memory compared with those with moderate/marked hippocampal sclerosis on multiple CVLT indices (recall measures, learning characteristics, and contrast measures). PMID- 8192850 TI - Parallel augmentation of hippocampal long-term potentiation, theta rhythm, and contextual fear conditioning in water-deprived rats. AB - The influence of water deprivation on hippocampal long-term potentiation (LTP), theta rhythm, and contextual fear conditioning in rats was examined. In Experiment 1, hippocampal EEG activity and perforant path LTP were assessed in pentobarbital-anesthetized rats. Water deprivation did not affect baseline cell excitability or low-frequency synaptic transmission in the dentate gyrus, but it increased the magnitude of perforant path LTP and elevated the proportion of theta rhythm in the EEG. In Experiment 2, rats were classically conditioned to fear a novel context through the use of aversive footshocks. Water deprivation facilitated the rate of contextual fear conditioning but did not alter the asymptote of learning. Experiment 3 demonstrated that the facilitation of contextual fear conditioning was not due to a change in unconditional shock sensitivity. These results suggest that water deprivation exerts an influence on contextual fear conditioning by modulating hippocampal LTP and theta rhythm and that these processes serve to encode contextual information during learning. PMID- 8192851 TI - Cognitive functions and aging in the dog: acquisition of nonspatial visual tasks. AB - Old, middle-aged, and young dogs were compared on discrimination and reversal learning and on acquisition of a delayed-nonmatching-to-sample (DNMS) test of recognition memory. DNMS acquisition was acquired more rapidly by young dogs. Reversal deficits were found between aged mixed-breed dogs and young beagles, but not between old and young beagles. Aged beagles also showed unexpected deficits in reward approach and object approach learning. Aged mixed-breed dogs did not show deficits in reward approach and object approach learning, but they learned the discrimination task more slowly than the age-matched beagles. A detailed analysis of response patterns indicated that once present, the development of side preferences contributed to deficits of old dogs in discrimination learning. In the discrimination reversal, old dogs were more persistent in responding to the previously rewarded stimulus object. Findings suggest that the dog, like other species, shows age-dependent deterioration in cognitive function, the extent of deterioration is a function of both task and previous experience, and at least part of the deterioration is a result of increased behavioral rigidity. Results also indicate that it is important to control for breed differences and previous experience. PMID- 8192852 TI - Delayed development of fear-potentiated startle in rats. AB - The developmental emergence of fear-potentiated startle was examined in rats ranging in age from 16 to 75 days. In Experiment 1, a pure tone served as the conditioned stimulus (CS) and an acoustic startle pulse served as the unconditioned stimulus (US) for fear conditioning. Fear-potentiated startle by the tone CS was observed in rats 23 days of age and older but not in rats 16 days of age. In Experiment 2, a light served as the CS. Rats 30 days of age and older showed fear-potentiated startle, whereas 23-day-old rats did not. The final experiment demonstrated that another behavioral index of fear, stimulus-elicited freezing, was observed earlier in development than fear-potentiated startle, confirming the effectiveness of the training procedure for conditioning fear. The results suggest that fear-potentiated startle is a relatively late-emerging response system, paralleling the development of conditioned autonomic changes (e.g., heart rate) rather than that of freezing. PMID- 8192853 TI - Effects of electrical stimulation of the amygdaloid central nucleus on neocortical arousal in the rabbit. AB - This study sought to determine whether electrical stimulation of the amygdaloid central nucleus (ACe) produces cholinergically mediated neocortical arousal manifested in the suppression of frontal cortex delta wave (1-4 Hz) activity. Stimulation in both anesthetized and conscious rabbits produced a suppression of delta activity that was accompanied by bradycardia and blocked by cholinergic antagonists. Stimulation of the adjacent putamen did not produce delta suppression, whereas stimulation of the adjacent ventral globus pallidus produced a suppression of shorter duration than that produced by ACe stimulation. The results suggest that the ACe influences neocortical arousal, which may be mediated by its influence on the activity of cholinergic neurons of the nucleus basalis. PMID- 8192854 TI - Is tube-escape learning by protozoa associative learning? AB - The ciliate protozoa, Stentor and Paramecium, have been reported to escape from the bottom end of narrow capillary tubes into a larger volume of medium with increasing rapidity over the course of trials. This change in behavior has been considered an apparent example of associative learning. This decrease in escape time is not due to a change in the protozoa's environment, their swimming speed, frequency of ciliary reversals, or the proportion of time spent forward or backward swimming. Instead, most of the decrease results from a decrease in the proportion of time spent in upward swimming. However, a similar decrease in upward swimming occurs when the task is altered to require escape from the upper end of the capillary tubes. Because the protozoa exhibit the same change in behavior regardless of the reinforcing stimulus, tube-escape learning is not associative learning. PMID- 8192855 TI - Different potential of cellular and viral activators of transcription revealed in oocytes and early embryos of Xenopus laevis. AB - Many protein domains for transcriptional activation also function when fused to a heterologous DNA binding domain. In mammalian/HeLa cells, we have previously characterized the activation domains of several transcription factors using GAL4 fusion proteins. Here we have tested their transcriptional activity in oocytes and developing embryos of the clawed toad Xenopus laevis. We find that the "acidic" C-terminal domain of the herpesvirus VP16 (= Vmw65) activator, which is active from yeast to man, is also very active in the two Xenopus systems. The constitutive nature of this viral domain may have evolved to be refractory to cellular defense mechanisms. By contrast, activation domains from cellular eukaryotic transcription factors (TFE3, ITF2, MTF-1) are differentially active in oocytes and early embryos. This indicates that their activity can be regulated by protein modification and/or availability of specific coactivators. We have also compared VP16 induced enhancement of transcription from remote and promoter proximal positions. In both oocytes and late blastula embryos, activation from a promoter-proximal position was more than 50 fold, while only a moderate stimulation (3-8 fold) was observed from remote positions. This may mean that frog oocyte and early embryos are not yet fully geared for gene control by remote enhancers, i.e. respond predominantly to close-by regulatory sequences. The fact that cellular enhancers are naturally located at various distances from the responsive promoters may thus be exploited by multicellular organisms for differential gene control at early and late stages of development. PMID- 8192856 TI - Purification and characterization of two putative HLA class II associated proteins: PHAPI and PHAPII. AB - In addition to their well defined role in presentation of processed antigen on the cell surface, class II molecules are able to transduce signals into the cell after binding of ligands. The cytoplasmic regions of class II molecules might function as docking sites for as yet unidentified proteins that are components of this signalling pathway. Here we report on two putative HLA class II associated proteins (PHAPI and PHAPII) which have been purified from the cytosolic fraction of the human lymphoblastoid B-cell line H2LCL using an affinity matrix composed of the synthetic biotinylated cytoplasmic region of the DR2 alpha chain immobilized on avidin agarose. The sequence obtained for PHAPI revealed a novel primary structure with a leucine/isoleucine rich N-terminal region. Protein data and the cDNA sequence obtained for PHAPII agree with the cDNA sequence of SET that has been described recently. Both PHAPI and PHAPII have an extended highly acidic C-terminal region. Based on their primary structure we speculate that PHAPI and PHAPII are involved in the generation of intracellular signalling events that lead to regulation of transcriptional activity after binding of a ligand to HLA class II molecules. PMID- 8192857 TI - Bikunin in rat plasma, lymph and bile. AB - Bikunin is a protease inhibitor consisting of a 16 kDa polypeptide and an 8 kDa chondroitin sulphate chain which has an apparent molecular mass of 60-70 kDa upon gel filtration. It is synthesized by hepatocytes and occurs in plasma, both in free form, and in complex with other polypeptides--mainly as the 180 kDa protein inter-alpha-inhibitor. Bikunin binds to proteases less avidly than other plasma inhibitors, making its role in the blood unclear. However, some observations indicate that bikunin has important functions outside the blood system. To assess its capacity to reach extravascular spaces, we have determined the total concentration of bikunin in plasma (0.17 mg/ml), lymph (31 micrograms/ml) and bile (0.2 microgram/ml). Quantitation after removal of complexed bikunin (inter alpha-inhibitor) by acid precipitation showed that the concentration of free bikunin in those fluids was 3, 1.4 and 0.05 micrograms/ml, respectively. These values yield a lymph/plasma ratio of free bikunin of 0.5, which is higher than expected for a protein of the hydrodynamic size and charge of bikunin. The bile/plasma ratio (0.02), however, is similar to that of other proteins of comparable size. The corresponding values for inter-alpha-inhibitor, 0.16 and 0.001, respectively, indicate that its capacity to pass through the vascular endothelium is relatively high whereas transfer to bile is restricted. Furthermore, we have found that in a perfusate of an isolated rat liver, the ratio of free to complexed bikunin was 30-40 times higher than in plasma, consistent with previous observations showing that free bikunin is cleared from the blood stream much more rapidly than inter-alpha-inhibitor. PMID- 8192858 TI - Transferrin-binding capacity by rat bone marrow populations containing different proportions of erythroid cells. AB - The transferrin-binding capacity of rat bone marrow cells and different erythroid enriched populations from rat bone marrow has been studied and compared with that previously reported for pure reticulocyte populations. Two components with different transferrin-binding capacities were found. The one with higher affinity was present mainly in erythroid cells and showed an association constant similar to that observed in reticulocyte populations. The component with a lower transferrin affinity was observed mainly in bone marrow fractions containing low proportions of erythroid cells. PMID- 8192859 TI - The role of the glucose/fatty acid cycle in the selective modulation of non oxidative and oxidative glucose disposal by oxidative muscle in late pregnancy. AB - Physiological insulin stimulation (induced by re-feeding) in late (19 to 20 days) pregnancy in the rat led to only partial reversal of starvation-induced increases in circulating fatty acid concentrations. The impaired suppression of adipose tissue lipolysis was associated with a clear attenuation of the activation of PDHa activity in oxidative skeletal muscles (diaphragm, soleus and adductor longus) in response to physiological insulin stimulation. In contrast, effects of late pregnancy to suppress glucose utilization were only modest in oxidative skeletal muscles, where a predominate fate of glucose under physiological insulin stimulation is glycogen formation. The ability of the pregnant rat to sustain glycogen repletion during physiological insulin stimulation was retained. Glucose utilization by the heart, which in virgin rats is particularly sensitive to increases in lipid-fuel supply and oxidation, bore a significant inverse relationship with the plasma fatty acid concentrations in late-pregnant rats. We conclude that an elevation in circulating fatty acid concentrations in late pregnancy provokes changes in glucose utilization by cardiac and skeletal muscle which are consistent with the operation of the glucose-fatty acid cycle. Importantly, these effects pertain under physiological hyperinsulinaemia. The relative insensitivity of glucose utilization by oxidative skeletal muscle to late pregnancy under conditions of physiological insulin stimulation presumably reflects the predominant use of glucose as a substrate for glycogen synthesis rather than as an energy substrate. PMID- 8192860 TI - Human alpha S1-casein like protein: purification and N-terminal sequence determination. AB - Casein components of human milk are generally reported to belong to the beta- and kappa-groups. In this research human casein fraction was obtained from pooled mature milk, either by ultracentrifugation or by acid precipitation. In both cases a minor component with a slightly higher mobility in SDS-PAGE than beta casein was identified. The protein was purified to homogeneity, the N-terminal sequence of the first 14 amino acid residues of this new human casein subunit shows a high degree of homology with the alpha s1-casein sequences from other species. PMID- 8192861 TI - Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. AB - Oxidation of lipoproteins is important for the initiation and propagation of the atherosclerotic lesion and may involve secondary oxidants derived from nitric oxide. Nitric oxide (NO) reacts at near diffusion limited rates with superoxide (O2-.) to form the strong oxidant, peroxynitrite (ONOO-). Nitration on the ortho position of tyrosine is a major product of peroxynitrite attack on proteins. Nitrotyrosine was detected in atherosclerotic lesions of formalin-fixed human coronary arteries with polyclonal and monoclonal antibodies. Binding was pronounced in and around foamy macrophages within the atheroma deposits. Nitration was also observed in early subintimal fatty streaks. Antibody binding was completely blocked by co-incubation with 10mM nitrotyrosine, but not by equivalent concentrations of aminotyrosine or phosphotyrosine. The presence of nitrotyrosine indicates that oxidants derived from nitric oxide such as peroxynitrite are generated in human atherosclerosis and may be involved in its pathogenesis. PMID- 8192862 TI - Kinetic characterization of affinity chromatography purified clostripain. AB - The cysteine protease clostripain, purified by affinity chromatography on a large scale, shows very high activity against BAEE using the titrimetric standard assay. Furthermore, titration of the active site with the irreversible inhibitor tosyl-lysyl-chloromethane resulted in a more than two times higher specific activity compared with literature data (Porter et al. (1971) J. Biol. Chem. 246, 7675-7682). Based on the molar enzyme concentration determined, the hydrolysis kinetics of the standard substrate BAEE were compared with those for the N alpha protected dipeptide ester Mal-Tyr-Arg-OEt. It was demonstrated from the kinetic data that the highly purified clostripain is the most active enzyme preparation available up to now. In contrast to the standard substrate, Mal-Tyr-Arg-OEt shows a threefold lower specificity constant. PMID- 8192863 TI - The role of the proximal CTAAT-box of the rat glucokinase upstream promoter in transcriptional control in insulin-producing cells. AB - Sequence analysis of the 5'flanking region of the beta-cell specific transcription unit of the rat glucokinase gene (r beta GK) revealed the presence of sequence motifs very similar to the IEB-(Far)-box and a CT-motif which play a crucial role in transcriptional control of insulin genes. 5'deletional analysis of the r beta GK proximal promoter element (localized between nucleotides -278 and -49) as well as site directed mutagenesis showed that both motifs are mutationally sensitive and contribute to transcriptional control in HIT M2.2.2 cells. The combination of the IEB-(Far)-like motif with the CT-box was unable to form a "mini-enhancer" similar to the Far-FLAT-element of the rat insulin I gene promoter but rather functions as a beta-cell specific control element in r beta GK expression. Electrophoretic mobility shift assays (EMSAs) and competition studies using oligonucleotides containing CT-motifs of rat insulin genes promoters, human insulin gene promoter, and rat amylin gene promoter showed similar binding patterns with nuclear extracts isolated from insulin-producing cell lines. These studies indicate that CT-motifs of rat glucokinase, insulin, and amylin gene promoters may bind similar--probably identical--nuclear factor(s) and may play a central role in the coordinated expression of these genes in insulin-producing cells. PMID- 8192864 TI - The insulin receptor: a protein kinase with dual specificity? AB - We have studied serine phosphorylation of the beta-subunit of highly purified human placental insulin receptors. Each purification step was analyzed with respect to phosphotyrosine and phosphoserine content, incorporated in the beta subunit of the insulin receptor. Independent of the purification state the analysis of the phosphoamino acids of the insulin receptor beta-subunit showed tyrosine and serine phosphorylation in an insulin dependent manner. In the presence of insulin up to seven phosphates per alpha beta-half receptor, indicating a ratio of Tyr(P) and Ser(P) of approximate 3:1 were incorporated, while in the absence of the hormone this ratio did not exceed 1:10. Comparison of the phosphorylation reactions on tyrosine and serine residues makes it highly probable that both phosphoryltransfer reactions obey the same hormone dependence. Half maximal incorporation of total phosphate in the receptor protein was about 5 minutes in contrast to the half maximal serine phosphorylation of about 8 minutes. Our data corroborate that autophosphorylation of serine residues is an intrinsic activity of the receptor kinase itself suggesting a dual-specificity type protein kinase. PMID- 8192865 TI - Papain digestion of crude Trichoderma reesei cellulase: purification and properties of cellobiohydrolase I and II core proteins. AB - The major cellulase components produced by Trichoderma reesei are composed of distinct catalytic and cellulose-binding domains. A simple two-step procedure is described for the purification of the catalytic domains, also termed core proteins (cp), of the major components, cellobiohydrolase (CBH) I and II. The novel aspect of this procedure is that native CBH I and II do not have to be purified initially. Papain digestion of a commercial T. reesei cellulase preparation followed by gel filtration on a Superdex 75 column resulted in the separation of fractions containing CBH I cp and CBH II cp; chromatofocusing purified the latter to homogeneity. N-terminal protein sequencing of CBH II cp provided good evidence for its identity. A comparison of the catalytic activity and cellulose-binding ability of these cp was made. A major difference between them was that CBH II cp bound to microcrystalline cellulose, unlike CBH I cp. CBH I cp readily hydrolysed the bond between the aglycone and cellobiose in p nitrophenyl cellobioside unlike the CBH II cp preparation. Neither CBH I cp nor CBH II cp had activity toward carboxymethylcellulose, but both were able to hydrolyse barley beta-glucan. It was also shown that incubation of cellulose fibres with native CBH I, CBH I cp or CBH II cp resulted in a smoothing of the fibre surface. PMID- 8192866 TI - Purification and characterization of an aminopeptidase from Lactobacillus casei subsp. rhamnosus S93. AB - An aminopeptidase of broad specificity was extracted by cell lysis of a selected strain of Lactobacillus casei subsp. rhamnosus during the late exponential phase. The enzyme was purified 195-fold from crude extract by using an f.p.l.c. system. Native and SDS/PAGE of the purified enzyme showed a single protein band of 89 kDa. The maximum aminopeptidase activity was observed at pH 7.0 and 39 degrees C. The enzyme hydrolysed a range of nitroanilide-substituted amino acids, as well as dipeptides, and accounted for most of the aminopeptidase activity found in cell free extracts. The enzyme activity was inhibited by metal chelators such as EDTA and 1,10-phenanthroline. Cobalt ions only stimulated aminopeptidase activity and were also able to re-activate the enzyme previously inhibited by metal chelators. The Km and Vmax. values of the aminopeptidase for leucine p-nitroanilide were 0.06 mM and 12.6 mmol/min per mg of protein respectively. This enzyme was stable over the pH range of 5-9 and below 45 degrees C. PMID- 8192867 TI - One-step isolation of a chitinase by affinity chromatography of the chitinolytic enzyme complex produced by Streptomyces kurssanovii. AB - One of the four chitinases with a molecular mass of 42 kDa existing in the chitinolytic enzyme complex produced by Streptomyces kurssanovii was separated in homogeneous form using one-step affinity chromatography on cross-linked and phosphorylated chitin-type sorbents. Three other chitinases were not selectively bound by the sorbents and were not obtained in homogeneous form. The affinity sorbents were shown to be stable over the time of separation and could be used repeatedly. PMID- 8192868 TI - Immobilization of beta-galactosidase on metal-chelate-substituted gels. AB - The use of copper, zinc, iron, nickel and calcium in three different chelating gels was investigated for preparing immobilized beta-galactosidase. The chelated ligands [Cu(2+)-iminodiacetate (IDA), Cu(2+)-Tris(carboxymethyl)ethylenediamine (TED), Ni(2+)-IDA and Fe(3+)-IDA] absorbed the protein so strongly that it can be considered a true immobilization. The obtained enzyme derivatives were investigated with regard to activity and stability. Enzymic activity was highly preserved in general for the TED derivates (90% when compared with that for Cu(2+)-TED). The immobilized Ni2+ derivatives were more stable to high temperature and to storage than the Cu2+ derivatives. Temperature-stability of the immobilized enzyme was very much improved by adding a strong metal-chelating gel such as carboxymethylated tetraethylenepentamine-agarose. The gel could be re used and reloaded after elution with chelator. beta-Galactosidase from Escherichia coli was purified using immobilized-metal-ion-chelate chromatography (i.m.a.c.). The potential use of beta-galactosidase immobilized on i.m.a.c. gels for technical purposes is discussed. PMID- 8192869 TI - Overview of cardiac electrophysiologic testing. AB - This article describes the basics of electrophysiologic (EP) testing. Included are the identification of a patient population amenable to EP testing, a routine setup for EP testing, and the common protocols performed during EP testing. The overview gives a general understanding of EP testing as well as insight into the patient's perspective. Commonly used EP terms are defined. PMID- 8192870 TI - Ablative therapy in the treatment of tachyarrhythmias. AB - Ablative therapy for treatment of tachycarrhythmias has developed rapidly in recent years due to an increased understanding of electrophysiologic mechanisms of arrhythmogenesis and improved modalities of destroying or isolating arrhythmogenic tissue. Radiofrequency catheter ablation is currently the most frequently performed type of ablative therapy. Less commonly, surgical procedures are performed to eradicate arrhythmogenic tissue. As more clinical experience is gained with these technologies for arrhythmia eradication, ablative therapy for treatment of tachyarrhythmias will continue to evolve. PMID- 8192871 TI - A parents' perspective: our needs and our message. AB - This article, written by parents, describes their fears and frustrations as the child they love is taken from the joyful family life that had been expected, to the terror of facing the possibility of death in a critical care situation. The parents want to help the medical team in healing their child, yet find themselves in a totally foreign environment in which they are often ineffective. By sharing the feelings experienced during their child's initial diagnosis and treatment, the authors hope that health care professionals will understand better the emotions parents are feeling and that parents can be helped to overcome their fears in order to better assume their role as part of the critical care treatment process. PMID- 8192872 TI - Transport of the neonate with suspected or diagnosed congenital cardiac disease. AB - Neonates with diagnosed or suspected congenital cardiac lesions generally require emergency transport to a tertiary care center shortly after birth. This article reviews the special needs of neonates with congenital cardiac defects who require this emergency transport. A case study is presented, and the special roles of nurses in referring institutions as well as nurses specializing in transport are addressed. PMID- 8192873 TI - Nursing implications of interventional device placement in pediatric cardiology and pediatric cardiac surgery. AB - The use of interventional devices to complete or augment repair of congenital heart lesions capitalizes on the collaborative skills of the cardiovascular team: cardiology, cardiovascular surgery, and nursing. Placement of devices, eliminating the requirement for surgical intervention, places new demands on nursing staff regarding patient and family preparation. Supporting families, if the inability to place a device occurs, is a critical function of the nursing staff. The experimental nature of the devices and the complexity of the disease places additional stress on the family and increases the demands of postimplantation nursing care. PMID- 8192874 TI - Recurrent ventricular tachycardia. AB - Recurrent ventricular tachycardia presents nurses with multiple challenges in terms of the knowledge of arrhythmia etiology, treatment, identification of potential problems, and physiologic and psychologic interventions before, during, and after an electrophysiology study. To assist in the understanding of arrhythmia etiology, the predominant electrophysiologic mechanisms for recurrent ventricular tachycardia are discussed. Also discussed are the procedures that can occur during an electrophysiology study and treatment options. Implications for nurses are discussed and include such factors as potential adverse physiologic and psychologic incidents that may be manifested in the pre- or postelectrophysiology study period. PMID- 8192875 TI - Nutritional issues in infants and children with congenital heart disease. AB - Congenital heart disease is often associated with a clinical picture of failure to thrive from unique nutritional issues. Poor weight gain, less than expected linear growth, and variances in normal development are commonly seen both in infancy and throughout childhood when defects are unrepaired. Major factors associated with disturbances in growth and development as well as a review of current therapeutic interventions are explored in this article. PMID- 8192876 TI - Mechanical support for congestive heart failure in infants and children. AB - Pharmacologic therapy is the primary intervention for congestive heart failure in children. When pharmacologic support is unsuccessful, however, the use of mechanical support is becoming more common. The use of intraaortic balloon counterpulsation, extracorporeal membrane oxygenation, ventricular assist devices, and abdominal compression devices in infants and children is increasingly becoming a viable option in pediatrics. Despite these advances, development of mechanical support for refractory CHF must continue for the development of ventricular assist devices and artificial hearts for infant and children as a bridge to transplant. PMID- 8192877 TI - Acquired heart disease in infants and children. AB - Discussed in this article are the presentations, treatments, and nursing implications for Kawasaki disease, cardiomyopathy, and acute myocarditis. The focus is on the symptoms and courses of therapies for these acquired heart diseases in children and on the critical care nurse's role in their care. PMID- 8192878 TI - Advanced case studies in hemodynamic monitoring: postoperative cardiovascular patients. AB - Pediatric patients with complex congenital cardiac defects present unique challenges in hemodynamic monitoring to the critical care nurse. An understanding of the hemodynamic alterations caused by both the underlying lesions and the surgical repairs is necessary to establish acceptable parameters in caring for these patients. In these complex patients, understanding expected deviations from normal ranges and integrating this information with clinical presentations is critical for individualizing effective interventions. An overview of hemodynamic monitoring and two advanced case studies are presented. PMID- 8192879 TI - Special management issues for adolescents and young adults with congenital heart disease. AB - Advances in diagnosis, medical management, and surgical treatment of patients with congenital heart disease (CHD) have resulted in a dramatic increase in the number of children surviving to adulthood. Nurses and physicians are starting to recognize adolescents and young adults with CHD as a growing subspecialty group with unique challenges and needs. The question of who should follow these patients remains unsettled, and it is not uncommon to find adolescents and young adults with CHD on both pediatric and adult units. The special management needs of this population are discussed as well as strategies for teaching and counseling. PMID- 8192880 TI - Chronic hypoxemia in children with cyanotic heart disease. AB - Hypoxemia, visible as cyanosis, is present in infants and children with congenital cardiac defects that result in arterial desaturation. Although many of these defects can be surgically repaired, some children remain cyanotic. Chronic cyanosis causes adaptive changes such as polycythemia and potentially damaging changes in other organ systems. This article reviews the assessment and management of patients with cyanotic congenital heart disease. The physiologic consequences and associated medical problems of chronic cyanosis are highlighted. Nursing implications in caring for cyanotic children and young adults are discussed. PMID- 8192881 TI - Postoperative rhythm disturbances. AB - Cardiac dysrhythmias in children after repair of congenital heart disease continue to challenge pediatric cardiovascular health care professionals. These rhythm disturbances, both bradyarrhythmias and tachyarrhythmias, can occur acutely and resolve, or they may become chronic, warranting more aggressive therapy. This article presents an overview of these acute and chronic rhythm disturbances, their associated treatments and interventions, and the nursing implications of caring for these children and their families. PMID- 8192882 TI - The patient with Wolff-Parkinson-White syndrome. AB - Wolff-Parkinson-White (WPW) syndrome is characterized by a classic ECG pattern and a history of palpitations, syncope, pre-syncope, or tachyarrhythmias. An electrophysiology study is an integral part of the diagnosis and treatment of this disease, and with the advent of catheter ablative techniques, WPW syndrome is now considered a curable disease. The critical care nurse needs to be aware of the acute and chronic treatment of this syndrome, the complications of therapy, and the educational needs of the patient and family. PMID- 8192883 TI - The patient with recurrent atrioventricular nodal reentrant tachycardia or chronic atrial fibrillation or atrial flutter. AB - Atrioventricular nodal reentry tachycardias, atrial fibrillation, and atrial flutter are common symptomatic arrhythmias encountered in clinical practice. The reentry mechanisms and pathophysiology of atrioventricular nodal reentrant tachycardias, atrial fibrillation, and atrial flutter are described. This article outlines the therapeutic approaches used in the acute phases of presentation. Nursing implications for patients admitted to intensive care/telemetry units are discussed. PMID- 8192884 TI - Patients with sinus node dysfunction or atrioventricular blocks. AB - Sinus node dysfunction and AV block constitute the underlying pathology for the majority of patients receiving permanent pacemakers. The predominate arrhythmia is bradycardia, and although rarely life threatening, patients may present with severe symptoms such as syncope or acute heart failure. In these situations, patients are admitted to the critical care or telemetry unit for monitoring and treatment. It is the responsibility of the critical care nurse to have an understanding of the clinical manifestations of sinus node dysfunction and AV block and to initiate appropriate interventions for symptomatic arrhythmias. PMID- 8192885 TI - Update on new antiarrhythmic drugs. AB - Although strides have been made in the surgical and technological management of arrhythmias, the widespread use of antiarrhythmic drugs continues as a therapeutic approach. Based on a review of cellular electrophysiology and the classification system of antiarrhythmic drugs, this article addresses the actions, indications, adverse effects, and nursing implications for new antiarrhythmic drugs. Nurses are provided with the essential information about these drugs so that safe and effective therapy can be achieved. PMID- 8192886 TI - Cardiac rhythm control devices. AB - More than 110,000 men, women, and children receive permanent implanted pacemakers annually in the United States alone, and thousands more receive implantable cardioverter defibrillators; more still are treated for a brief period with temporary pacing in critical care settings. Because of the prevalence of rhythm disturbances and the growing use of devices as a means of therapy, critical care nurses may reasonably expect to care for patients receiving or already using such equipment. Knowledge of its function is a useful tool at the bedside. This article discusses basic attributes and behaviors of these devices and methods of diagnosing and dealing with the most commonly seen difficulties associated with them. PMID- 8192887 TI - Control of glycogenolysis and effects of exercise on phosphorylase kinase and cAMP-dependent protein kinase in rainbow trout organs. AB - To analyze the mechanisms of glycogen phosphorylase control in organs of the rainbow trout Oncorhynchus mykiss, activities of glycogen phosphorylase kinase (GPK) and cAMP-dependent protein kinase (PKA), as well as levels of cAMP, were quantified. The complete cascade for activating glycogen phosphorylase was present in trout organs and all components were activated in white skeletal muscle and liver during exhaustive swimming exercise. GPK and PKA showed the highest activities in the liver, being three- and four-fold higher than corresponding activities in white muscle. Exercise stimulated a 60% increase in GPK activity in the liver and a 40% rise in white muscle. Furthermore, the amount of active PKA rose from 12 to 21% in the liver and from 32 to 57% in white muscle after exhaustive exercise and the cellular levels of cAMP increased by 50% in the liver and 70% in white muscle of exercised fish. Other organs (heart, gill, brain, kidney) showed little or no change in these parameters as a result of exhaustive exercise. GPK activity in liver, muscle, and heart extracts was strongly stimulated by in vitro incubation with the catalytic subunit of mammalian PKA, activity rising by 6- to 7-fold in white muscle extracts and 2- to 2.6-fold in liver and heart extracts. This occurred in extracts from both control and exercised fish and suggested that even in fish exercised to exhaustion, the maximal enzymatic potential for activation of glycogenolysis was not expressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192888 TI - The effect of the heat shock response on ultrastructure of the centrosome of Drosophila cultured cells in interphase: possible relation with changes in the chemical state of calcium. AB - Previous observations have shown that the heat shock response affects the centrosome function. We compared the ultrastructural organization of the centrosome in control (23 degrees C) and heat-shocked (37 degrees C, 50 min) interphase Drosophila cells to detect the nature of the lesions that could alter this organelle. The centrosome apparatus showed only minor modifications after the stress and the architecture of the centrioles appeared unaffected. The main difference concerned the organization of pericentriolar material which appeared more condensed and clotted. In extreme cases this material seemed to collapse on the centrioles. Recent reports proposed that Ca2+ concentrations could modify the distribution of pericentriolar material. In this study, we measured the changes in total and bound calcium in control or heat-shocked cell samples. The hyperthermia stress induced an increase of about 80% in global calcium. However, there was a decrease of about 50% in bound calcium. A heat shock stress seemed therefore to promote a change from the bound to the free state for a noticeable proportion of the element. As a preliminary hypothesis, these changes in the chemical state of calcium could be related to alterations in the pericentriolar material and thus with the functional inactivation of the centrosome. This view is also supported by calcium analysis on early Drosophila embryos. Contrary to cultured cells, Drosophila embryos did not present a stress inactivation of centrosomes. Equally, a heat shock did not disturb the bound calcium level in embryos. PMID- 8192889 TI - Identification and localization of G(i) alpha 3 in the clonal adipocyte cell lines HGFu and Ob17. AB - The HGFu and Ob17 cell lines, derived from adipose tissue of lean (+/?) and ob/ob mice, respectively, express several G-protein peptides. Investigation of the expression and subcellular localization of the G(i) alpha 3 subunit showed that this peptide is associated with the Golgi apparatus. These findings indicate a role for this subunit in vesicular traffic and are in agreement with the view of the adipocyte as a secretory cell. PMID- 8192890 TI - Influence of exogenous growth factors on the expression of plasminogen activators by explants of normal and healing rabbit ligaments. AB - In this investigation we have demonstrated that specific growth factors are able to modify plasminogen activator (PA) activity in explants from both normal and healing ligaments. Specifically, the addition of insulin-like growth factor 2 (IGF-2; 100 ng/mL) and transforming growth factor beta 1 (TGF-beta 1; 2.5 ng/mL) to explants of unoperated and healing ligaments resulted in a decrease in both PA and PA--PA-binding protein complex in conditioned medium from several tissues, and particularly in medial collateral ligament (MCL) scar tissue. This effect was observed in the explants from 3-, 6-, and 12-week healing scar tissue. In addition, IGF-2 and TGF-beta 1 influenced PA release from MCL tissue derived from the unoperated knee joint of 3-week healing animals. In contrast, basic fibroblast growth factor (b-FGF; 10 ng/mL) and IGF-1 (100 ng/mL) did not cause a detectable alteration of PA and PA--PA-binding protein complex activity in any of the healing or unoperated ligaments analyzed. These results indicate that specific growth factors are able to modify the activity of cells in explants of ligament and healing ligament in a distinct manner. PMID- 8192891 TI - Rate of alteration of hepatic mixed-function oxidase system in rats fed different dietary fats. AB - Studies were carried out to evaluate and relate the rate of alteration in mixed function oxidase system with the changes of the fatty acid composition of rat microsomes induced by different dietary lipids. Male weanling rats were fed from day 21 to 120 with a commercial rat diet or a semisynthetic diet containing no fat or 10% fat consisting of peanut-rapeseed oil, sunflower oil, or salmon oil. In rats fed a fat-free diet, the cytochrome P-450 concentration and aniline hydroxylase, aminopyrine N-demethylase, and NADPH-cytochrome-c reductase activities of liver microsomes at 120 days were, respectively, 26, 16, 10, and 24% lesser than those of rats fed the control diet. However, cytochrome b5 concentration and NADH-cytochrome-b5 reductase activity were, respectively, 33 and 43% higher than those of the control group at the same time. When rats were fed the sunflower oil diet, the cytochrome P-450 concentration and NADH cytochrome-b5 reductase activity at 120 days were, respectively, 11 and 23% lesser than those of control group. But the cytochrome b5 concentration was 10% higher than that of the control group. In rats fed the fish oil diet, the cytochrome P-450 concentration and NADPH-cytochrome-c reductase, aniline hydroxylase, and aminopyrine N-demethylase activities at 120 days were, respectively, 30, 48, 41, and 31% higher than those of rats fed the control diet. These enzymes were correlated very well (0.84 < r < 0.93), P < 0.05 with dietary sigma polyunsaturated fatty acids (n-3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192892 TI - Ageing, differentiation, and gene expression in rat epididymal preadipocytes. AB - Ageing results in decreased replicative potential of preadipocytes, as well as reduced capacities for the lipid accumulation and increases in lipogenic enzyme activities during differentiation of preadipocytes into fat cells. To determine whether decreased differentiation is associated with decreased levels of mRNA for differentiation-dependent genes and whether early as well as late components of the differentiation programme are affected by ageing, we measured beta-actin, alpha-tubulin, lipoprotein lipase, and glycerol-3-phosphate dehydrogenase mRNA levels in undifferentiated and differentiated epididymal preadipocytes from 3-, 17-, and 24-month-old Fischer 344 rats. During ageing, diminished differentiation related changes occurred in mRNAs affected early (actin, tubulin), midway through (lipoprotein lipase), and late (glycerol-3-phosphate dehydrogenase) in the preadipocyte differentiation process. Hence, early as well as late phases of the differentiation programme were affected by ageing. The effects involved changes in gene transcription or mRNA processing. Our results were not consistent with the hypothesis that age-related decreases in replication are caused by an increased tendency for cell differentiation. PMID- 8192893 TI - Purification and kinetic characterization of pickerel liver alcohol dehydrogenase with dual coenzyme specificity. AB - A major alcohol dehydrogenase isozyme that displays dual coenzyme specificity has been purified from pickerel liver by ion-exchange, gel filtration, and affinity chromatographic procedures. The purified enzyme is chromatographically and electrophoretically homogeneous. It is dimeric and possesses common physical properties shared by other liver alcohol dehydrogenases. Phosphorus-31 nuclear magnetic resonance spectroscopy demonstrates that NADP+ binds to two coenzyme sites of the pickerel enzyme. Steady-state kinetic studies suggest that pickerel liver alcohol dehydrogenase catalyzes NAD(P)(+)-linked ethanol oxidation via a random pathway. While the NADP+ reduction involves the formation of an abortive complex at high NADP+ concentrations, the NAD+ reduction at low NAD+ concentrations follows an ordered Bi-Bi mechanism with NAD+ being the leading reactant. PMID- 8192894 TI - Multifunctional activities of pickerel liver alcohol dehydrogenase. AB - A major isozyme of pickerel liver alcohol dehydrogenase has been purified to homogeneity. The enzyme, in addition to catalyze NAD(P)(+)-linked dehydrogenation of alcohols, also mediates dismutation of aldehydes and hydrolysis of esters. Steady-state kinetic studies and chemical modifications of the pickerel liver enzyme with respect to its esterolytic and dismutative activities were carried out. Pickerel liver alcohol dehydrogenase catalyzes hydrolyses of p-nitrophenyl esters via a Uni-Bi mechanism, with alkanoic acids as the last product released. Modifications of Cys and Lys suppress the esterolytic activity. A random mechanism with the formation of dead-end complexes is implicated for the dismutation of octanal catalyzed by pickerel liver alcohol dehydrogenase. Two amino acid residues, Cys and His, are involved in the dehydrogenation as well as dismutation reactions. The present study identifies a regulatory function of Lys for the multifunctional activities of liver alcohol dehydrogenase. When the Lys residue is specifically glucosylated, the dehydrogenase activity increases. Its esterase activity decreases, while the dismutase activity remains unchanged. PMID- 8192895 TI - Increased phosphatidic acid and decreased lysophosphatidic acid in response to thrombin is associated with inhibition of platelet aggregation. AB - Thromboxane A2, produced from the arachidonic acid released from platelet phospholipids by phospholipase A2, stimulates platelet aggregation. It remains unresolved whether additional products of platelet phospholipase A2 might promote aggregation. To address this question, we have used aspirin-treated platelets to block thromboxane A2 formation and studied the influence of the phospholipase A2 inhibitor U10029A on platelet aggregation and secretion in response to thrombin. U10029A at 100 microM markedly inhibited platelet aggregation, but had no effect on platelet secretion. Since this concentration of U10029A effectively blocked lysophosphatidic acid (LPA) formation, LPA was added and found to substantially reverse the inhibitory effect of U10029A in these platelets. Furthermore, the action of U10029A was not due to inhibition of phosphatidate phosphohydrolase because U10029A, unlike propranolol, did not inhibit this enzyme. Although it is not possible to conclusively rule out an effect of U10029A in addition to its inhibition of phospholipase A2, our results reveal that a product of phospholipase A2 other than thromboxane A2 is important for platelet aggregation, but not for secretion in response to thrombin. Our data suggest that this product is LPA. Since the amount of phosphatidic acid (PA) increased dramatically concurrent with inhibition of platelet aggregation, it is safe to conclude that PA has no direct role to promote platelet aggregation in response to thrombin. PMID- 8192896 TI - Lithium preserves F-actin from the disarrangement induced by either DNase I or cytochalasin D. AB - Light scattering at 546 nm, which is mainly related to the presence of rodlike particles longer than 50 nm, showed that Li+ accelerates the formation of actin filaments. Intermolecular cross-linking with N,N'-1,4-phenylene-bismaleimide proved that the observed enhancement in the light-scattering intensity is caused by the increase in the concentration of actin oligomers, which gradually elongate to form longer filaments. DNase-I-related F-actin disassembly was reduced in the presence of lithium ions, as demonstrated by fluorimetric and viscometric experiments. Li(+)-F-actin showed an apparently similar behaviour when exposed to cytochalasin D. We confirm that Li+ acts on actin polymerization by stabilizing actin nuclei and polymers. The stabilization of cytoskeletal polymers really appears as one of the mechanisms by which lithium ions influence some of the cell activities. PMID- 8192897 TI - Glutathione synthetase from the fission yeast. Purification and its unique heteromeric subunit structure. AB - Glutathione (GSH) synthetase (EC 6.3.2.3) was purified from the fission yeast Schizosaccharomyces pombe L972h- and from the GSH synthetase deficient mutant MN101/pYS41, which harbors a plasmid containing the GSH synthetase gene of the fission yeast. GSH synthetase is expressed at 10 times higher the amount in MN101/pYS41 than in wild-type L972h-. The purified enzyme gave a single band on polyacrylamide gel electrophoresis in the absence of sodium dodecyl sulfate (native PAGE). The molecular weight of this enzyme was determined to be 1.2 x 10(5) by Sepharose CL-6B gel filtration. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) revealed that this enzyme was composed of two kinds of subunits, A (M(r) = 33 x 10(3)) and B (M(r) = 26 x 10(3)), and existed as a heterotetramer (A2B2). The enzyme purified from the wild type fission yeast, which did not harbor the plasmid, showed the same electrophoretic mobilities on both native PAGE and SDS-PAGE and similar catalytic properties under standard conditions. This enzyme is most active at 45 degrees C and pH 8.0-8.5 with 20 mM Mg2+ + 10 mM ATP and 50 mM K+. The strict requirement for the monovalent cation is rather specific for the enzymes from yeasts. The presence of sugar components in the enzyme is also observed, similar to that in the rat kidney enzyme. PMID- 8192898 TI - Calcium ions reverse a latency period induced by bovine serum albumin in the time course of phospholipase A2 action on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine liposomes. AB - The time course of hydrolysis of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine liposomes in the gel phase catalyzed by porcine pancreatic phospholipase A2 was studied at 1 mM NaCl and variable CaCl2 concentrations, in the presence of delipidated bovine serum albumin. It has been found that the duration of the latency induced by bovine serum albumin shows an inverse dependence with CaCl2 concentration. As we showed previously, the induction of a lag phase by bovine serum albumin is related to its ability to sequester the fatty acid newly released by hydrolysis. Based on this and on our observation that there is an inverse dependence between the length of the latency period and the interfacial calcium ion concentration, it is interpreted that, while a direct effect of bovine serum albumin is the diminution of the liposome negative surface charge density by sequestration of the fatty acid released during hydrolysis, an indirect effect could be the decrease in the surface Ca2+ concentration. This, in turn, should diminish the enzyme binding to the lipid-water interface. The appearance of a latency phase seems to be the final consequence of these events. PMID- 8192899 TI - Regulation of low density lipoprotein receptor and 3-hydroxy-3-methyl-glutaryl CoA reductase activities are differentially affected in Niemann-Pick type C and type D fibroblasts. AB - Defective regulation of intracellular cholesterol metabolism has been investigated in cultured fibroblasts from two subtypes of Niemann-Pick type II disease: the panethnic Niemann-Pick type C (NPC) and the Nova Scotia type D (NPD). Cell extracts from NPC and NPD fibroblasts cultured in lipoprotein deficient medium exhibited activities of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase that were two-fold greater than in normal cells. Addition of serum resulted in only a 15% decrease in HMG-CoA reductase activity within 6 h in these cells, compared with a decrease of 80% in normal fibroblasts. The initial rate of return to maximal values for the first 6 h after removal of serum was similar in all three cell types; thereafter, the rate was faster in the mutant fibroblasts. Binding and internalization of 125I-labeled low density lipoprotein (LDL) was not decreased within 12 h of incubation of NPC fibroblasts with serum, while a decrease of 50% was observed for both NPD and normal fibroblasts over this time period. Northern blot analysis also indicated a slower decrease in steady-state LDL receptor mRNA in NPC relative to normal and NPD cells. In all three cell types, inhibition of HMG-CoA reductase with mevinolin had no effect on serum stimulated cholesterol esterification, while inhibition of acyl-CoA:cholesterol acyltransferase with Sandoz 58-035 did not influence HMG-CoA reductase activity, indicating that defects in these regulatory mechanisms are independent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192900 TI - Assembly of adenovirus-specific nuclear inclusions in lytically infected HeLa cells: an ultrastructural and cytochemical study. AB - Adenoviruses (Ads) are nuclear DNA viruses that remodel host nuclear structure and function and induce formation of a variety of nuclear inclusions within which Ad DNA is replicated and transcribed. In this study, we have examined inclusion assembly by electron microscopy of samples stained conventionally or with bismuth to detect phosphoproteins. Small dense fibrillar bodies (DFBs) appeared very early associated with interchromatin granule (ICG) clusters. Somewhat later, similar DFBs lay near amorphous, loosely fibrillar structures that were moderately electron dense and showed little bismuth deposition. These clear fibrillar bodies (CFBs) enlarged and DFBs became embedded in their surface. At later stages, CFBs and DFBs were again dissociated. DFBs seen very early were poor in phosphoproteins, but later DFBs, whether embedded in the CFBs or lying near them, were intensely bismuth stained. DFBs and CFBs were less prominent once assembled virions were seen. At this late stage, virions were generally associated with moderately dense, slightly bismuth positive, irregularly shaped fibrillar inclusions that have previously been identified as viral genome storage sites. In addition, very dense fibrillar bodies, consisting usually of an electron-dense fibrillar shell and a less dense fibrogranular core, were observed at all but the earliest stages of infection, often at some distance from CFBs. There was also a major reorganization of host components during infection, including chromatin condensation, reduction of nucleolar volume and aggregation of the fibrillar regions at the nucleolar surface, and increased prominence of ICG clusters. A model is proposed for the assembly of Ad replication factories. PMID- 8192901 TI - Role of proteolysis in apoptosis: involvement of serine proteases in internucleosomal DNA fragmentation in immature thymocytes. AB - Three chemically distinct serine, but not cysteine, protease inhibitors (phenylmethylsulphonyl fluoride, N-tosyl-L-phenylalanylchloromethyl ketone and 3,4-dichloroisocoumarin) prevented, in a dose-dependent manner, the characteristic apoptotic internucleosomal DNA cleavage (DNA ladder) typically observed in thymocytes in response to dexamethasone and teniposide VM-26. This effect was not the result of a direct inhibition of the Ca2+,Mg(2+)-dependent endonuclease, since oligonucleosomal DNA cleavage occurred in the presence of these inhibitors in isolated nuclei. The proteolytic step occurred at a very early stage of apoptosis, and preincubation of thymocytes with the inhibitors before dexamethasone or teniposide VM-26 were added irreversibly suppressed ladder formation. This implied that the cellular effector(s) of these compounds preexisted and were not resynthesized in response to the inducers of apoptosis. Serine protease inhibitors also suppressed apoptotic cell shrinkage and complete nuclear collapse, suggesting that these morphological changes were directly related to internucleosomal fragmentation of DNA. However, the serine protease inhibitors did not prevent high molecular weight DNA cleavage (> 50 kilobases) that preceded the ladder formation and thymocytes still died by apoptosis. This supported the view that internucleosomal DNA cleavage, considered to be the biochemical marker of apoptosis, might in fact be a late and dispensable step and that the newly described high molecular weight DNA cleavage might be a better indicator of apoptosis. PMID- 8192902 TI - Aberrant behaviors of young boys with fragile X syndrome. AB - To determine whether aberrant behaviors described in boys with fragile X syndrome distinguish them from other boys with developmental disabilities, we asked the primary caregivers of 55 boys with fragile X and 57 matched controls to complete five behavioral questionnaires. Twenty-one items distinguished the groups. Principal components analysis (PCA) yielded five behavioral clusters: abnormal language, tactile defensiveness, poor self-control, poor eye contact/shyness, and hand flapping. Boys with fragile X were found times more likely to have both tactile defensiveness and abnormal language. The presence of these abnormal behaviors in boys with developmental delays warrants further assessment for fragile X. PMID- 8192903 TI - Profiles and development of adaptive behavior in children with Down syndrome. AB - The profiles and developmental trajectories of adaptive behavior were cross sectionally examined in 80 children with Down syndrome ages 1 to 11.5 years using the Vineland Adaptive Behavior Scales. Profile findings indicated a significant weakness in communication relative to daily living and socialization skills. Within communication itself, expressive language was significantly weaker than receptive skills, especially when children's overall communicative levels were above 24 months. One to 6-year-old children showed significant age-related gains in adaptive functioning, but older subjects showed no relation between age and adaptive behavior. There was, however, increased variability within this older group, implying that not all children plateau in adaptive development during the middle childhood years. Implications for development in Down syndrome and intervention programs were discussed. PMID- 8192904 TI - Allocation of attention and task difficulty. AB - Individuals with and without mental retardation did a dual task procedure designed to investigate how task difficulty influenced the allocation of attention. The primary task required semantic category decisions. Subjects sorted cards according to whether the object pictured on the card belonged to a target category. The easy decision task used basic level categories (horse and hammer). The difficult decision task used superordinate categories (animals and tools). While making decisions, subjects were required to signal detection of auditory probes. Response times to the probes were used to index attention to the primary task. Subjects without mental retardation allocated more attention to the difficult task. Those with mental retardation gave similar attention to the easy and difficult tasks. Possible explanations for their failure to allocate attention in accordance with task difficulty were discussed. PMID- 8192905 TI - Facilitation and inhibition effects in visual selective attention processes of individuals with and without mental retardation. AB - Adolescents with and without mental retardation participated in a visual selective attention task. They were required to identify one of two letters presented to them on the basis of color. We manipulated the relation between target and distractor letters on successive trials. A target letter could have been a target on the preceding trial, a distractor on the preceding trial, or not appear on the preceding trial. Subjects without mental retardation exhibited facilitation when the target was identical to the target on the preceding trial and inhibition when the target was a distractor on the preceding trial. Subjects with mental retardation also exhibited facilitation when the target was identical to the target on the preceding trial but not when it had been a distractor on the preceding trial. The inefficient suppression processes may result in performance deficits for individuals with mental retardation across a variety of tasks. PMID- 8192906 TI - Lewis Carroll's formula for calendar calculating. AB - One of the extraordinary skills occasionally displayed by individuals of low intelligence (so-called idiots savants) is the ability to name, within seconds, the day of the week for any given date, sometimes over a range of centuries. A number of scholarly papers contain references to formulas that can be used in making this calculation, but none cites one of the earliest published methods, that of Lewis Carroll. However, formulas such as Carroll's are too complex to be self-taught by idiots savants and, consequently, cannot account for their remarkable performance. Alternative explanatory hypotheses were briefly discussed. PMID- 8192907 TI - Short-term longitudinal study of maternal ratings of temperament in samples of children with Down syndrome and children who are developing normally. AB - Ratings of temperament for 32 children with Down syndrome and 44 children who were developing normally over the developmental range from 12 to 36 months were compared. Mothers completed the Toddler Temperament Scales and/or the Bates Infant/Child Characteristics Questionnaire at two time points. Analyses tested for diagnostic group differences in temperament ratings. Multivariate repeated measures analyses of variance, with diagnosis and developmental age as grouping variables, were run for both instruments. For the Toddler Temperament Scales, no between-subjects main effects of diagnosis or interactions were significant; however, a significant multivariate main effect for diagnosis was obtained for the Bates Scales. Ordering consistency for the two samples was considered separately. Cross-time correlations were generally significant; however, relations tended to be of greater magnitude in the normally developing group. Results suggest that the development of temperament, as assessed with maternal ratings, follows a common path in these two groups. PMID- 8192908 TI - Incidence of significantly altered pain experience among individuals with developmental disabilities. AB - Absence of basic pain behaviors when an injury or illness is typically painful suggests that the experience of pain may be significantly altered. In the present study third-party reporting of injury/illness incidents was used to estimate the incidence of pain insensitivity/indifference and provide evidence of its impact. A significantly elevated pain threshold was noted for 25.2% of 123 individuals with developmental disabilities. Those with more severe mental retardation were also more likely to display signs of pain insensitivity or indifference. These individuals risk avoidable death and increased physical disability as a result of failure to recognize and respond to illnesses and injuries that would be painful for others. Implications for rehabilitation practitioners and medical personnel were discussed. PMID- 8192909 TI - Evaluation of an intervention program: relation between children's phonology and parents' communicative behavior. AB - Parents of 9 preschoolers with Down syndrome participated in a training program focusing on phonological skills. Three of the children were producing multiword utterances, but their speech was characterized by jargon and/or inconsistent errors. The remaining 6 children had very few spoken words or were mute; some relied on a Makaton sign vocabulary. Parents attended twelve 3-hour training sessions. Videotapes of parent-child interactions (made before, during, and after the program) were analyzed for number and type of children's phonological errors and rating of parents' therapeutic skills. Results showed that measures of the children's phonological abilities were correlated with their parents' interactional communication skills. PMID- 8192910 TI - Oral feeding treatment of children with chronic food refusal and multiple developmental disabilities. AB - This research concerned the treatment of chronic food refusal in 2 children with multiple developmental disabilities. Therapeutic intervention consisted of a multicomponent treatment package that included the (a) elimination of feeding "demands" that provoked child agitation, (b) incorporation of sensory stimulation as contingent reinforcement, and (c) gradual introduction of the requirements for oral consumption. Each child received treatment during individualized training sessions and, subsequently, under naturalistic mealtime conditions. Consistent oral consumption was achieved rapidly by both children. Results were maintained at follow-up assessments ranging from 4 to 12 months. PMID- 8192911 TI - Oral health of institutionalized individuals with mental retardation. AB - A random 10% (n = 702) of the residents of the Texas Department of Mental Health and Mental Retardation (TXMHMR) institutions were given dental examinations by the first author. Findings were compared with results from a similar survey of 1,077 residents by the same investigator 9 years earlier. Data were analyzed for oral pathology, unmet dental needs, contribution of dental care to habilitation, and effectiveness of the dental service system. Some improvements were found in dental condition, although the results were sometimes difficult to interpret. Some differences may be related to changes in client age and average length of stay and to a shift toward institutionalization of individuals with more severe disabilities. Other differences appear to be the result of better dental care in state institutions. PMID- 8192912 TI - Metabolic responses of the dopaminergic system during hypoxia in newborn brain. AB - The purpose of this review is to describe the relationship between the dopamine and amino acid neurotransmitter systems and cortical oxygen pressure during different levels of cerebral hypoxia using newborn piglets as an animal model, adding new data from our laboratory. The extracellular dopamine increases as the oxygen pressure in the cortex decreases. The relationship between oxygen pressure and dopamine levels is the same whether the hypoxia is induced by reduced FiO2 (high-flow hypoxia) or by hypocapnia-induced cerebral vasoconstriction (low-flow hypoxia). Thus it appears that, particularly in mild hypoxia, the extracellular level of dopamine depends primarily on the oxygen concentration in the tissue with minimal influence of parameters such as blood flow and pH. There is no "oxygen reserve" in the brain of newborn piglets and the extracellular levels of dopamine in the striatum increase almost linearly with decrease in oxygen pressure, with even small decreases in oxygen pressure resulting in increased dopamine levels. In contrast, the changes in extracellular concentrations of the excitatory amino acids glutamate and aspartate are variable and transient. In a majority of 2- to 5-day-old piglets even very low oxygen pressures in the brain did not result in significant alterations in the extracellular levels of glutamate and aspartate. These changes in the dopaminergic system may contribute directly and indirectly to the neuronal damage that occurs during hypoxic/ischemic insult and reoxygenation in newborn brain, particularly in the striatum. A variety of mechanisms are discussed by which dopamine, in particular extracellular dopamine, can increase cellular toxicity. PMID- 8192913 TI - Allopurinol-enhanced postischemic recovery in the isolated rat heart involves repletion of high-energy phosphates. AB - The effects of allopurinol (AP) on functional and metabolic recovery of the isolated rat heart after global ischemia were studied. Hearts were subjected to aerobic perfusion (30 min), cardioplegic infusion (5 min), normothermic ischemia (37 min), and reperfusion (50 min) which was started with secondary cardioplegic infusion (10 min). AP was injected into rats (44 mg/kg body wt ip 2 h before heart excision) and added to cardioplegic solution (2 mM) prior and after ischemia. AP treatment significantly improved postischemic recovery of the function and reduced the leakage of lactate dehydrogenase from reperfused hearts. These beneficial effects were accompanied by a better preservation of tissue content of ATP, the total adenine nucleotides, phosphocreatine, and the total creatine at the end of reperfusion. Inhibition of xanthine oxidase by AP substantially decreased pre- and postischemic release of xanthine and uric acid and increased postischemic release of hypoxanthine into the coronary effluent. Despite this, AP-treated hearts did not exhibit a reduction in hydroxyl radical adduct formation in the effluents at reperfusion assessed by the spin-trap measurements. The results suggest that AP may protect the heart from ischemia/reperfusion injury due to enhanced energy provision rather than by prevention of oxygen-derived free radical formation. PMID- 8192914 TI - An evaluation of the measurement of the activities of complexes I-IV in the respiratory chain of human skeletal muscle mitochondria. AB - The measurement of individual respiratory chain complexes is an important component of the investigation of diseases due to mitochondrial dysfunction. We have evaluated assays which measure complexes I to IV in human skeletal muscle mitochondria and in addition optimized these assays to provide sensitive and reliable diagnostic techniques, particularly in situations where a partial interruption at a single complex needs to identified. Using several established methods of membrane disruption we have found that optimal activities of complexes I and II are obtained by freeze-thawing the mitochondria in hypotonic potassium phosphate buffer, whereas complex III and IV activities are markedly increased by the addition of the detergent n-dodecyl-beta-D-maltoside. Complex I activity is measured in the presence of 2.5 mg.ml-1 bovine serum albumin, which increases rotenone sensitivity, and we have shown that NADH-cytochrome b5 reductase makes an important contribution to the rotenone-insensitive NADH-ubiquinone oxidoreductase activity. Complex II activity is measured after preincubation of the mitochondrial fraction with succinate to fully activate the complex. Complex I and III activities are dependent upon the length of the isoprenoid chain of the ubiquinone and ubiquinol, respectively. These assays have been used to establish a control range. PMID- 8192915 TI - Subregional and intracellular distribution of NADP-linked malic enzyme in human brain. AB - High total activity (expressed as mumol/min/g of wet tissue or per milligram of DNA) and differential subregional distribution of NADP-linked malic enzyme was found in autopsy specimens of human brain. Striatum showed the highest activity of malic enzyme, which was two- to five-fold higher than that in other human organs tested. High activity was also found in frontal cortex, while the lowest activity of the enzyme in the central nervous system was found in cerebellum, substantia alba, and corpus callosum. In striatum, frontal cortex, pons, and cerebellum more than 80% of total malic enzyme activity was localized in the mitochondrial fraction, while in substantia alba and corpus callosum approximately 60% of the enzyme activity was present in the mitochondrial fraction. Relatively high specific activity of malic enzyme was found in a crude mitochondrial fraction isolated from various regions of human brain. The highest specific activity was found in the mitochondria isolated from striatum (more than 100 nmol/min/mg of mitochondrial protein); the lowest, but still high (approximately 32 nmol/min/mg of mitochondrial protein) was present in corpus callosum. These data and the different ratios of citrate synthase to mitochondrial malic enzyme activities found in different regions of brain suggest that human brain mitochondria, like the mitochondria isolated from other mammalian brains, are extremely heterogenous. A possible role of mitochondrial malic enzyme in human brain metabolism is discussed. PMID- 8192916 TI - Melatonin-like immunoreactivity in the presence of different chemicals as determined by the radioimmunoassay. AB - To determine the nature of the molecule(s) that is responsible for the melatonin like immunoreactivity (MLI), we measured the effect of pretreatment of plasma samples with detergents, reducing agent, and proteinase K. Nonidet P-40 Triton X 100, and ethylacetate extraction had no effect, while sodium deoxycholate, sodium dodecyl sulfate, beta-mercaptoethanol, ether extraction, proteinase K, and temperature increased the MLI. Since the radioimmunoassay (RIA) was sensitive to proteinase K, ionic detergents, and a reducing compound, we hypothesize that a proteinaceous molecule might be responsible for this MLI. We compared our column procedure for RIA of plasma melatonin (1) with procedures involving extraction with either ethylacetate or ether. In our hands preextraction of samples with organic solvents caused a loss of immunoreactivity. We also found that passing samples through the column is more efficient in eliminating interference in the melatonin assay than extracting samples either with ethylacetate or ether. PMID- 8192917 TI - Evaluation of serum and tissue levels of beta-carotene. AB - Interest in beta-carotene (BC) has increased as studies show that low dietary or serum BC is associated with increased risk of cancer. Patients with oral epithelial dysplasia had serum and oral mucosa punch biopsy samples taken before supplementation of 30 mg/day of beta-carotene and after 6 and 9 months of supplementation. BC was analyzed for 28 patients by high-performance liquid chromatography. At baseline, serum BC and gender accounted for 48% of tissue BC variance: Tissue BC = -0.13 + 0.08(Serum BC) + 1.21(Sex) with sex as male = 0 or female = 1. Following supplementation, serum BC had an exponential relationship to tissue BC which accounted for 52% of tissue variance: Tissue BC = 1.15 + 5.7 x 10(-5)(Serum BC)2 + 3.91(Sex). Women had higher mean concentrations of serum and oral mucosal BC before and during supplementation. The need for oral mucosal sampling may be eliminated by the correlation between serum and tissue BC. PMID- 8192918 TI - Bone marrow transplantation demonstrates that carbonic anhydrase II deficiency limited to bone marrow-derived cells affects ammonium chloride tolerance in mice. AB - Bone marrow transplantation (BMT) in mice was utilized to determine the relative importance of carbonic anhydrase II (CA II) deficiency in blood compared to kidney in the pathogenesis of the ammonium chloride intolerance observed in CA II deficient mice. "Normal" BMT experiments utilized normal donors and CA II deficient recipients (NL-->DEF), "reverse" BMT experiments utilized CA II deficient donors and normal recipients, and control BMT experiments utilized normal mice with a hemoglobin polymorphism (Hbb d/s). Unstressed urinary pH was not significantly altered by normal or reverse BMT, nor was any change induced by control BMT. However, DEF-->NL mice showed markedly altered weight changes when placed on oral ammonium chloride, an effect apparently secondary to dehydration due to decreased water intake. In addition, some CA II-deficient mice have a urinary concentrating defect. Red blood cell and kidney CA II deficiency contribute additively to these effects. PMID- 8192919 TI - Molecular diagnosis of 21-hydroxylase deficiency: detection of four mutations on a single gel. AB - Previous studies of the molecular basis of 21-hydroxylase deficiency have shown four common gene conversion mutations in exons 7 and 8. Current molecular diagnostic protocols use allele-specific oligonucleotide hybridization (ASOH) to individually detect each of these mutations and the corresponding normal alleles. This method is costly, labor intensive, and may not provide quantitative results. To expedite molecular diagnosis in families with 21-hydroxylase deficiency, we have designed and implemented single-strand conformational polymorphism (SSCP) analysis. We applied SSCP analysis to 12 families in whom mutations in exons 7 or 8 had been previously identified by ASOH. Using a single polymerase chain reaction (PCR) amplification, unique conformers can be assigned to three mutations: V281L, Q318X, and R356W. The fourth mutation, T insertion at nucleotide 1761, was detected by heteroduplex analysis of the same PCR product. Thus, we were able to identify all four mutations using a single PCR product on a single gel. PMID- 8192920 TI - Influence of antioxidants on arachidonic acid metabolism and platelet function. AB - Studies from our laboratory demonstrated that the free radical scavenger, nitro blue tetrazolium, and iron chelators, such as dypyrydil, are potent inhibitors of arachidonic acid oxidation and platelet function. In the present study, we have evaluated the effects of known antioxidants, such as butylated hydroxyanisol (BHA), butylated hydroxytoluene (BHT), and diphenylamine, on arachidonic acid metabolism and platelet function. Diphenylamine, a common dye intermediate used in hair color formulations, was the most potent inhibitor of arachidonic acid metabolism by platelet cyclooxygenases. Diphenyl and BHA were also potent inhibitors of arachidonic acid oxidation. Other diphenyl analogues and BHT were relatively poor inhibitors of arachidonic-mediated platelet activation. Results of this study, as well as those of our earlier studies, suggest that antioxidants and iron chelators prevent arachidonic acid metabolism and alter platelet function by interfering with the heme/arachidonic acid interaction and blocking cyclooxygenase metabolites essential for the formation of thromboxane A2, a potent platelet agonist. PMID- 8192921 TI - Anti-zeta antibody screening for alpha-thalassemia using dried filter paper blood. AB - The most common alpha-thalassemia in Southeast Asian or Southern Chinese populations is the (--SEA) double alpha-globin deletion. Couples heterozygous for (--SEA) have 25% risk for hydrops fetalis from loss of all four alpha-globin genes. The (--SEA) deletion spares the embryonic zeta-globin genes and causes traces of zeta-peptide to persist throughout life. A colorimetric monoclonal anti zeta antibody test for raised zeta-peptide has detected the (--SEA) deletion in liquid blood samples, but not deletions of the entire alpha-globin region with loss of the zeta-globin genes. Eluates from dried blood spots had the same anti zeta antibody color reaction as whole blood, even after storage at 4 degrees C for up to 77 days. The anti-zeta antibody test was positive in 24 of 91 microcytic samples (mean corpuscular hemoglobin < 24 pg), including four with iron deficiency; it was negative in 26 provisionally diagnosed alpha-thalassemia 1 heterozygotes and all 32 nonmicrocytic samples. Southern blot analysis and a specific SEA-polymerase chain reaction test confirmed that 18 anti-zeta antibody positive samples and 1 anti-zeta antibody-negative sample had the (--SEA) deletion. Two anti-zeta antibody-negative microcytic samples had the (--Fil) total alpha-globin region deletion, 2 had single alpha-gene deletions, 22 others may also have had a total alpha-region deletion. Hence specificity was very high and sensitivity was 95%. The anti-zeta antibody test can detect the (--SEA) deletion in dried blood samples, even after prolonged storage. This simple inexpensive test can conveniently screen samples collected at a distance from a central laboratory. PMID- 8192922 TI - Protein kinase C inhibitors enhance differentiation of rat adipocyte precursor cells in serum-free culture. AB - The involvement of protein kinase C in differentiation of rat adipocyte precursor cells in serum-free culture was evaluated by using various protein kinase inhibitors. Induction of adipose conversion, which was maximal after 10 days of culture in the presence of 5 micrograms/ml insulin, 10 micrograms/ml transferrin, and 200 pM triiodothyronine, was inhibited by the addition of protein kinase C inhibitors, H-7 and staurosporine, in a dose-dependent fashion with the maximal effect at 10 microM and 10 nM, respectively. Inhibition of adipocyte differentiation by 12-O-tetradecanoylphorbol 13-acetate (10(-8) M), an activator of protein kinase C, was reversed by a concomitant addition of either 10 microM H 7 or 10 nM staurosporine. HA1004, a potent inhibitor of cAMP- and cGMP-dependent protein kinases, with minimal inhibitory activity on protein kinase C, did not affect adipose conversion. Furthermore, H-89, another isoquinoline derivative with a selective inhibitory action on cAMP-dependent protein kinase, was without effect on cellular differentiation. These results indicate that the potentiation of adipogenesis by H-7 and staurosporine is mediated by suppression of protein kinase C and that protein kinase C is involved in adipocyte differentiation in an inhibitory fashion. PMID- 8192923 TI - Effect of acute cocaine injection on the extracellular level of dopamine, blood flow, and oxygen pressure in brain of newborn piglets. AB - The present study examined the effects of acute cocaine administration on oxygen pressure in the vasculature of the cortex as well as on blood flow and extracellular levels of dopamine in the striatum of newborn piglets. The oxygen dependent quenching of phosphorescence was used to continuously monitor oxygen pressure in the vasculature of the cortex. Following acute cocaine injection (1.5 mg/kg iv) the cortical oxygen pressure rapidly decreased from 36.3 +/- 1.2 to 32.9 +/- 1.4 Torr and remained at the lower level during the 120 min of postinjection period during which measurements were made. Blood flow in striatum, as determined by laser Doppler, was decreased by 8-10% at 5 min after injection of cocaine. This decrease in blood flow was statistically significant up to 40 min postinjection. Extracellular dopamine, measured using in vivo microdialysis, showed a large increase after cocaine injection. The dopamine level increased from 14 +/- 7 to 88 +/- 21 pmol/ml by 15 min after drug administration, then decreased to 45 +/- 11 pmol/ml and remained stable for the 120 min post-injection period. The mechanism(s) by which the increase in the extracellular level of dopamine occurred may include a direct effect of cocaine on the dopamine transporter and/or an indirect effect due to the decrease in cerebral oxygenation and blood flow. The increase in extracellular dopamine can be responsible for several alterations in neuronal metabolism with potentially deleterious effects on neuronal function. PMID- 8192924 TI - [Potassium channels in saccular hair cells in the bullfrog]. AB - By means of cell-attached and excised inside-out patch clamp techniques, we studied ion channels of the basolateral membrane of hair cells isolated from the bull-frog's sacculus. Three types of K+ channels were recorded, with conductances of 19-23PS, 46PS and 78PS respectively. The reversal potential was -56 +/- 20mV. The kinetics of the high- and low-conductance type K+ channels was different. The former was identified as KCa and the latter was suspected as KDR or KIR. They have important function in the sensory coding of hair cells. PMID- 8192925 TI - [Scanning electron microscopy of cochlear blood vessels in guinea pig]. AB - The microvascular architecture of the cochlea of guinea pig was investigated by the vascular corrosion casting and electron microscopy methods. Results showed that the cochlear vessels were fully filled with the plastic material. With this technique we could clearly demonstrated the overall three-dimensional spatial picture of the cochlear vessels. The anatomy of lateral radiating arteriole and its branches, as well as the drainaging veins of lateral cochlear walls were carefully studied. PMID- 8192926 TI - [Functional and morphological changes of the cochlea in guinea pigs during anoxia]. AB - The influence to endocochlear potential (EP), cochlear microphonics (CM) and summating potential (SP), the ultrastructural changes of the cochlea and the survival time of hair cells in guinea pigs during anoxia and suffocation were investigated. We found that: 1) The stria vascularis was much more sensitive to anoxia than hair cells. 2) 85% CM was highly sensitive to anoxia, and 15% kept stable until the destruction of outer hair cells. 3) -SP turned into +SP after anoxia. 4) EP was related to the destruction of outer hair cells and the disappearance of CM. PMID- 8192927 TI - [Analysis of evoked otoacoustic emissions in patients with high frequency cochlear hearing loss]. AB - Evoked otoacoustic emissions (EOAE) and auditory brainstem evoked response (ABR) were tested in patients with high frequency cochlear hearing loss and subjects with normal hearing. Results showed that: 1. In the normal group, the main component of EOAE varied between 0.5-5kHz. 2. There was a close correlation between the pure-tone audiogram figure and EOAE spectrum. 3. The I/O function curves of EOAE displayed non-linear characteristics and a trend of saturation with higher stimulus levels in the normal group. In the patient group the growth rates of EOAE and ABR were remarkably higher than those in the normal group with high stimulus levels. It suggests that the abnormal EOAE are probably relevant to the recruitment phenomenon in cochlear hearing loss. PMID- 8192928 TI - [Changes of audio-vestibular parameters in experimental endolymphatic hydrops]. AB - Endolymphatic hydrops were produced in twenty guinea pigs by obliteration of the endolymphatic sac. Auditory and vestibular functions were investigated before and after the obliteration. Our experimental data showed that: 1) the SPVN (sinusoidal pendular vestibular nystagmus) frequency decreased after the obliteration of the lymphatic sac; 2) the CAP response threshold to filtered clicks and the CAP response threshold to clicks were both elevated after obliteration of the endolymphatic sac; and 3) 2f1-f2 DPO (distortion product otoacoustic emissions) amplitudes, as induced by primary tones of adequate frequency and level rations, decreased as endolymphatic hydrops occurred. PMID- 8192929 TI - [Histochemical study of intrinsic laryngeal muscles in neonates]. AB - The motor end-plates and muscle fiber types in muscles of cricothyroid, posterior cricoarytenoid, thyroarytenoid were in five neonates and two adults studied by staining with acetylcholinesterase (AChE) and succinic dehydrogenase (SDH). The muscle fibers in neonate could be classified into three types: red, white and intermediate. The diameters of muscle fibers were different, with the white muscle fiber widest and the red ones narrowest. Each of the laryngeal muscles was composed of three muscle types in proportion. The motor end-plate showed a concentrated distribution band. PMID- 8192930 TI - [Effect of lymphokine-activated killer cells of head and neck tumors in vitro and in nude mice]. AB - Human lymphokine-activated killer (LAK) cells were prepared by culturing normal peripheral blood mononuclear cells (PBMC) for 4 days with or without added recombinant interleukin 2 (rIL-2) and assayed for anti-tumor activity against established squamous cell carcinoma lines of the head and neck (SCCHN) in vitro and in nude mice. The results showed that LAK cells had a stronger cytotoxicity than control cells to different SCCHN in vitro. In vivo, LAK cells almost completely inhibited the growth of HEP-2 tumor in nude mice and resulted in an inhibition rate of 81.6% (P < 0.01 with control cells). Our data indicate that LAK cells may be useful in the treatment of patients with head and neck tumors. PMID- 8192931 TI - [Complications of endoscopic sinus surgery]. AB - Endoscopic sinus surgery has become popular during recent years. Here is a report of complications of endoscopic sinus surgery among 150 patients. Seven patients had complications, including one nasolacrimal duct injury, one temporary blindness, one orbital hematoma as a result of trauma to the lamina papyracea, two orbital infections, one CSF leakage and one death probably due to laceration of the internal carotid artery. The complication rate was 4.6%, and the mortality rate 0.6%. We conclude that the knowledge of anatomy, good training, and meticulous surgical technique are very important, and that endoscopic sinus surgery in patients with extensive lesions should be handled with care, especially in patients with bleeding or bone destruction involving the lateral wall of sphenoid sinus and skull base. PMID- 8192932 TI - [AgNORs staining of exfoliated cells in the nasopharynx for diagnosis of nasopharyngeal cancer]. AB - AgNORs were investigated in exfoliated cell smears from nasopharynx and in sections of biopsied tissues of NPC patients. It showed increased tendency of AgNOR activity that was significantly higher in carcinomas than in benign tumors, chronic nasopharyngitis, and normal nasopharyngeal tissues. This suggests that AgNOR technique of exfoliated cells might be useful for NPC diagnosis, follow-up of NPC patients, and identification of precancerous lesions of the nasopharynx. PMID- 8192933 TI - [Comparative study on cytotoxicity of lymphocytes from different tissues in laryngeal cancer]. AB - PBL, TdLNL and TIL from twelve laryngeal cancer patients were cultured with rIL-2 for five to seven days and developed into LAK cells and TILs. The killing activities of LAK cells and TILs against K562 cells were measured by the method of 3H-TdR Incorporation. The results were as follows. After activation in vitro by rIL-2, PBL, TdLNL and TIL augmented in volume, became irregular in shape, and displayed all karyokinetic characteristics. Activated TILs showed cytotoxic activities against tumor cells; TdLNL isolated from the tumor-draining lymph nodes were in large quantity. TdLNL could be cultured with rIL-2 alone for a long period, it may be the best way to harvest large quantity of LAK cells. LAK cells, from PBL and TdLNL had the same killing activities against K562 (P > 0.05). TIL activated by rIL-2 in short period also displayed killing activities against K562, but was less potent than LAK cells from PBL and TdLNL (P < 0.05). Lymphocytes of different sources could be effectively induced into LAK cell. On the basis of our experiments, the TdLNL could be used as a best source of LAK cells in the adoptive immunotherapy for laryngeal cancer. PMID- 8192934 TI - [Quantitative immunohistochemical study of ras oncogene product P21 in laryngeal carcinomas and its clinical importance]. AB - Thirty cases of laryngeal carcinoma and 6 cases of vocal polyps and normal laryngeal epithelium were studied by immunohistochemical methods. The results showed that P21 content in laryngeal carcinoma increased markedly than that in normal laryngeal epithelium and vocal polyps (P < 0.01). It suggests that laryngeal carcinoma is correlated with the activation of ras oncogene. There was no significant correlation between P21 contents and pathological classification of laryngeal carcinoma, but increase in contents was correlated with metastasis and recurrence. PMID- 8192935 TI - [Detection of human papillomavirus DNA with biotinylated probes in laryngeal papillomas by in situ hybridization]. AB - This study used the technique of in situ hybridization (ISH) to detect human papillomavirus (HPV) 6, 11, 16 and 30 DNA genome in 45 paraffin and 3 frozen specimens of laryngeal papillomas. The results showed 17 HPV 6 and 19 HPV 11 positive in 45 paraffin specimens. The HPV 6 infection in juvenile laryngeal papillomas was significantly higher than that in adult lesions. On the other hand, there was no significant difference for HPV 11, and between male and female patients. Only one of the 3 frozen sections was positive for HPV 11 in juvenile recurrence case. HPV 16 and 30 were negative in all cases. The positive signal was always confined to the nuclei in superficial squamous epithelium of laryngeal papillomas. The results showed that the ISH technique could provide direct evidence of the association of HPV and juvenile or adult laryngeal papillomas. PMID- 8192936 TI - [The long-term clinical results of laryngeal cancer treated with tracheo pharyngeal anastomoses]. AB - From 1978 to 1991, 90 cases of laryngeal cancer had been treated with reconstructive tracheo-pharyngeal anastomoses. Among these cases, 78 were male and 12 female; the sex ratio was 6.5:1, the youngest case was 35 years old, and the eldest 87. The clinical staging was as follows: Supraglottic cancer 41 cases (stage II 23, stage III 16, stage IV 2), glottic cancer 47 (stage II 15, stage III 27, stage IV 5), subglottic cancer 2 (stage II 1, stage IV 1). The 3, 5, 10 year-survival rates were 76.6%, 60.8% and 18.2% respectively. Decannulation was successful in 42 cases (46.7%). All patients could take food via mouth and speak without training. PMID- 8192937 TI - [Antiepileptic drugs]. PMID- 8192938 TI - [Cerebral circulatory improvers and metabolic activators]. PMID- 8192939 TI - [Magnetoencephalographic observation of cortical spreading depression elicited by experimental focal brain ischemia in rats]. AB - It has recently been reported that focal ischemia induced by occlusion of unilateral middle cerebral artery provoked direct current (DC) potential deflection in the cortical infarct rim. DC potential deflection is suggested to be one of the deteriorating factors for ischemic damage. We aimed to elucidate whether a direct current magnetoencephalography (MEG) can noninvasively record DC potential deflection in focal brain ischemia or not. Fourteen male Wistar rats were used for this study. After anesthesia with pentobarbital, rats were subjected to transcranial occlusion of left middle cerebral artery by electrocauterization. Three rats showed recurrent DC potential deflections, like cortical spreading depression (CSD). The direct current MEG deflections always followed DC potential obtained by electrically recorded electrocorticograms. Mean repetition interval of DC potentials was 574 +/- 178 (SD) seconds, and their mean amplitude was 1266 +/- 789 fT. Time course of DC potentials induced by focal ischemia resembles to CSD induced by KCl application to cerebral cortex. Our observation suggests that DC magnetoencephalography is one of the useful tools for non invasive recording direct current potential deflections which are impossible to be obtained by conventional EEG techniques, and that this method will be a powerful diagnostic tool for focal brain ischemia. PMID- 8192940 TI - [Protective effect of nicardipine hydrochloride on the evolution of delayed neuronal death--an immunohistochemical study]. AB - Alteration of evolution of delayed neuronal death in the gerbil after intraperitoneal injection of nicardipine was investigated by using immunohistochemistry for microtubule associated protein (MAP) which enables early detection of ischemic injuries. Male Mongolian gerbils were subjected to intraperitoneal injection of nicardipine at concentrations of 0.01-10 mg/kg and subsequent occlusion of bilateral carotid arteries for 5 min. Extent of the lesions estimated by immunohistochemistry for MAP was reduced at the dosages of 0.2 mg/kg nicardipine as compared with control, while lesser or larger amounts have failed to protect the brain tissue from ischemic insults. Furthermore, pre- and postoperative treatment of 0.2 mg/kg of nicardipine two times daily succeeded to partially attenuate the development of delayed neuronal death in gerbils which underwent ischemia for 5 min and subsequent reperfusion for 4 days. These results indicate that optimal concentration of nicardipine ameliorates delayed neuronal death, presumably because of the increase of cerebral blood flow and intervention of intracellular influx of calcium ions. PMID- 8192941 TI - [Clinicopathoradiological studies in 15 cases of megadolichobasilar anomaly]. AB - We clinicopathoradiologically assessed 15 angiographically diagnosed megadolichobasilar anomalies. Nine of the patients were male and 6 were female; their average age was 61 years. Eleven patients presented with cerebral ischemic attacks, other two complained of trigeminal neuralgia and the remaining two suffered severe headaches. Twelve of the patients had severe hypertension. Vertebral angiography revealed marked elongation of the basilar artery with severe tortuousity and dilatation. The average distance from the dorsum sellae to the basilar artery bifurcation on the lateral view was 24.7 mm, and the average maximum diameter of the basilar artery was 8.6 mm. Aneurysmal dilatation of the basilar artery was also observed in four cases. In 14 of the 15 patients CT scans revealed characteristic findings, such as tubular high density mass with evident contrast enhancement extending from the ventral medulla to the interpeduncular cistern. The outcome was extremely poor, with five deaths and four patients with severe dementia. In the two autopsy cases, enlarged internal lumens could be observed despite severe atheroscrelotic changes, such as intimal thickening by atheromas. PMID- 8192942 TI - [Differential effects of isosorbide dinitrate and nitroprusside on pial vessel diameter in cats]. AB - Changes in pial vessel diameter combined with regional cerebral blood flow (CoBF) during infusion of vasodilating drugs, isosorbide dinitrate (ISDN) 5 micrograms/kg/min and nitroprusside (NTP) 5 micrograms/kg/min, compared with haemorrhagic hypotension were studied in cats anesthetized with halothane (1.0%). Pial arteries and veins were measured by image-splitting technique and were each divided into three groups according to the reference diameter: I; < 50 microns, II; 51 < microns < 100, III; 101 < microns. With either drug, the mean blood pressure (mBP) decreased by 10-20%. There was significant decrease in cerebral vascular resistance with ISDN compared with haemorrhagic hypotension while CoBF (H2 clearance) remained unchanged. Dilatation of pial arteries depending on vessel size with ISDN was two-hold compared with haemorrhagic hypotension without any change in all veins. Consistent and significant dilation of veins (I and II) was observed only during NTP infusion. These findings indicate the differential effect of ISDN and NTP on pial arteries and veins. PMID- 8192943 TI - [Neurocutaneous melanosis--a case report]. AB - Neurocutaneous melanosis is a rare congenital phacomatosis characterized by the presence of large or multiple congenital melanocytic nevi and benign or malignant pigmented cell tumors of the leptomeninges. A 14-month-old boy was admitted with a recent history of vomiting and drowsiness. He was found to have multiple congenital melanocytic nevi. Gd-enhanced MRI showed ventriculomegaly and leptomeningeal enhancement in the ambient cistern. CSF cytology revealed abnormal cells with pigmented granules. A diagnosis of hydrocephalus with malignant neurocutaneous melanosis was made. The patient was treated with combination chemotherapy (DAV therapy, ACNU intrathecal perfusion therapy, interferon beta therapy) while controlling intracranial pressure by CSF drainage, but in spite of treatment he died due to rapid progression of leptomeningeal infiltration. Postmortem examination revealed meningeal malignant melanomas predominantly at the base of the brain and benign meningeal melanosis over the cerebral cortex. Newborn infants or infants with large or multiple congenital melanocytic nevi should be carefully followed, especially for the first two years. When hydrocephalus or convulsions occur in patients with skin lesions, Cd-enhanced-MRI and careful CSF cytology studies should be performed to detect meningeal abnormalities. PMID- 8192944 TI - [Report of a case of small cell lung cancer associated with Lambert-Eaton myasthenic syndrome and subacute cerebellar degeneration--with a review of the Japanese literature]. AB - We report a patient with small cell lung cancer associated with Lambert-Eaton myasthenic syndrome (LEMS) and subacute cerebellar degeneration (SCD). The patient was a 71-year-old man suffering from weakness of the limbs and a gait disturbance who developed limb ataxia and dysarthria one month after admission. Electrophysiologic studies confirmed the diagnosis of Lambert-Eaton myasthenic syndrome. Chest X-rays 2 months after admission revealed an abnormal shadow, and small cell lung cancer was diagnosed on the basis of biopsy specimens. Anti voltage-gated calcium channel antibody was positive. Anti-Yo and -Hu antibodies were negative. The patient was treated by plasmapheresis and chemotherapy, which resulted in a transient improvement in the LEMS symptoms but not in the SCD. Fifteen cases of LEMS associated with SCD have been reported in the Japanese literature, and all were accompanied by small cell lung cancer. We discuss the frequency of association with LEMS and SCD and the effects of plasmapheresis and chemotherapy in both diseases. PMID- 8192945 TI - [Unilateral supranuclear abducens palsy in a pineal tumor]. AB - A 13-year-old boy complained of frequent headaches and diplopia on rightward gaze. A CT scan demonstrated hydrocephalus and a non-homogeneous enhancing mass in the pineal area, leading to a diagnosis of pineal tumor. The physical examination revealed no abnormalities. On neurological examination, there were a right homonymous hemianopsia and slight choked disc in both optic fundi. His right eye was slightly adducted on primary gaze. On right lateral gaze, his right eye could not move beyond the midline and showed gaze paretic nystagmus, whereas his left eye could move fully in all directions. The abducens palsy could be overcome by the oculocephalic maneuver or caloric test. Interestingly, his right eye could abduct when his left eye was covered. From these finding, this was labelled a supranuclear abducens palsy. The convergent nystagmus was observed. Rightward OKN (quick phase to right) of the right eye was abolished with and without the left eye covered, while leftward OKN of the right eye was preserved. Pursuit to right was disturbed. After removal of the tumor, the gaze palsies disappeared. It is postulated that the supranuclear lateral gaze palsy was caused by impairment of supranuclear control by involvement of lateral gaze pathways to gaze center coursing near the oculomotor nucleus. PMID- 8192946 TI - [A 78-year-old man with progressive gait disturbance, dysphagia, and dementia]. AB - We report a 78-year-old man with progressive gait disturbance, dementia, and dysphagia. He was apparently well until 75 years of age in 1989 when he had an insidious onset of gait disturbance. In October of 1991, he was treated with levodopa and amantadine HCl in another hospital, but he developed visual hallucination right after these medications, and the drugs were discontinued. He also developed difficulty in swallowing with frequent aspiration pneumonia. He was admitted to our hospital on January 13, 1992. On admission, the patient was chronically ill Japanese man; his blood pressure was 118/70 mmHg, body temperature 35.4 degrees C, and heart rate 72 and regular. No anemia or jaundice was noted; lungs were clear and no heart murmur was audible. The abdomen was flat but rigid to palpation without tenderness; no organomegaly was noted. On neurologic examination, he was alert but disoriented to all spheres; he was apparently demented and the score of the mini-mental test was 11. He did not appear to have aphasia or apraxia. Cranial nerves appeared intact, but he had a mask-like face and a slight limitation in the upward gaze; his voice was small. He was unable to stand or walk; he showed marked akinesia and moderate rigidity in his neck and the trunk. Deep reflexes were generally elicited normally or slightly weakly. Plantar response was extensor on the left and flexor on the right. No grasp reflex was present. Sensory examination showed questionable loss of touch in the glove- and -stocking distribution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192947 TI - Concept analysis of pain: implications related to nursing diagnoses. PMID- 8192948 TI - Altered thought processes and sensory/perceptual alterations: a critique. AB - Concerns about the clinical usefulness of altered thought processes and sensory/perceptual alterations--and the resulting avoidance of these two diagnoses--led to a study to determine how expert nurses differentiate between the diagnoses and how the diagnoses are used in practice. The authors developed a questionnaire and mailed it to 128 members of NANDA who had identified themselves as experts in the diagnoses; sixty-six (52%) responded. Conclusions were that the defining characteristics for altered thought processes were cognitively oriented and those for sensory/perceptual alterations were perceptually oriented. The overlap of defining characteristics, such as change in problem-solving ability, makes differential diagnosis a difficult task. PMID- 8192949 TI - Modification of the diagnostic content validity model. AB - Diagnostic content validation of nursing diagnoses is a recommended means to confirm the defining characteristics necessary to establish a specific nursing diagnosis. The diagnostic content validity model has been used in numerous studies to develop lists of major and minor defining characteristics recommended by experts as being present in patients with specific diagnoses. The authors provide an overview of the diagnostic content validity model, review the meaning and purposes of content validity, discuss problems with information processing, and suggest revisions to the diagnostic content validity model. Incorporation of these changes may improve the usability of nursing diagnoses in clinical practice, education, and research. PMID- 8192950 TI - Content validation of impaired skin integrity and urinary incontinence in the home health setting. AB - The purpose of this study was to examine content validity of two nursing diagnoses in the home health setting: impaired skin integrity and altered urinary elimination: total incontinence. Eighty-two home health nurses rated the importance of each of the defining characteristics for the two nursing diagnoses. Diagnostic content validity scores (DCV) were calculated for each defining characteristic for both diagnoses using the method described by Fehring (1986). Four characteristics for each diagnosis had DCV scores greater than .75, indicating characteristics were critical indicators for the diagnosis. Erythema, denuded skin, disruptions of dermal and epidermal tissue, and lesions were critical indicators for impaired skin integrity. Lack of awareness of incontinence, constant flow of urine, lack of awareness of bladder cues to void, and incontinence refractory to other treatments were critical indicators for alteration in urinary elimination: total incontinence. PMID- 8192951 TI - Research validation of nursing diagnoses: how much progress? PMID- 8192952 TI - Nursing diagnosis research: computer-aided research in nursing. AB - The authors describe the development of a research tool for studies on nursing diagnosis by the Computer-Aided Research in Nursing (CARIN) project. The tool, a computerized assessment guide, has reliable and valid items for the identification of patient problem areas. The patient information in the assessment guide, nursing diagnoses identified by the clinical nurse specialist, and a statistical interface are linked in a customized computer program for the CARIN project, providing a system capable of analyzing patient problems from several perspectives. The system provides an accurate assessment and subsequent analysis of patient problems, as well as large data sets. Implications for the future of nursing diagnosis research are discussed. PMID- 8192953 TI - MR imaging of cerebrospinal fluid dynamics in health and disease. On the vascular pathogenesis of communicating hydrocephalus and benign intracranial hypertension. AB - The CSF flows in the aqueduct and at the foramen magnum were examined in 5 patients with communicating hydrocephalus (HC) and in 10 with benign intracranial hypertension (BIH) as well as in 5 healthy volunteers. As compared to normal individuals, the aqueductal flow in HC was about 10 times larger and the cervical flow was half as large. In BIH the CSF flows were not different from those of normal volunteers. The decreased arterial expansion as reflected in the reduced cervical flow in HC may be due to pathologic changes in the arteries and paravascular spaces. The large aqueductal flow in HC reflects a large brain expansion, causing increased transcerebral mantle pressure gradient and ventricular dilatation. In BIH there is a normal brain expansion (aqueductal flow) and consequently no ventricular dilatation. It is argued that BIH be caused by an obstruction on the venous side, as opposed to the vascular alterations in HC, which are on the arterial side. PMID- 8192954 TI - Preembolization functional evaluation in supratentorial cerebral arteriovenous malformations with superselective intraarterial injection of thiopental sodium solution. AB - Superselective intraarterial injections of thiopental sodium solution for evaluation of local brain function were performed before embolization in 38 consecutive patients with supratentorial arteriovenous malformations to evaluate the role of the test using thiopental sodium solution. Thiopental sodium (30-50 mg) was injected in 68 arteries (44 middle cerebral arteries, 13 anterior cerebral arteries, 7 posterior cerebral arteries, 3 external carotid arteries, and 1 thalamo-perforating artery) through superselective microcatheters just before the injection of cyanoacrylate mixture for the embolization. The test was negative in 57 arteries and there were neurologic dysfunctions in 3 of them after embolization. The neurologic deficits in these cases were caused by reflux of embolic material, spasm of the main arterial trunk, or neglected mild sensory change, respectively, and there was no real false-negative test. The embolization could not be performed due to positive test in 9 arteries. Two arteries with positive tests but acceptable symptoms were embolized and the same neurologic deficits developed immediately after embolization. There was no local arterial complication by an injection of the thiopental sodium solution. All neurologic deficits caused by positive tests developed immediately and were completely relieved within 5 min without specific management. Superselective intraarterial injection of thiopental sodium solution is a safe and reliable test for the evaluation of local brain function before embolization of supratentorial arteriovenous malformations. PMID- 8192955 TI - Prognostic significance of contrast enhancement and tumor demarcation at CT of squamous cell carcinomas of the oral cavity and oropharynx. AB - A retrospective analysis of the CT examinations of 45 patients with squamous cell carcinomas of the tongue, floor of the mouth and tongue base with long-term follow-up is presented. The aim of the study was to determine whether differences in tumor contrast enhancement and tumor demarcation at contrast-enhanced CT were correlated to prognosis in terms of posttreatment residual tumor or local recurrence. Ill-defined tumor margins were by means of multiple regression analysis significantly correlated to local failures (p = 0.043). This feature was, however, not associated with a significant decreased survival. The degree of tumor contrast enhancement did not parallel variations in the histopathologic composition of the tumors. PMID- 8192956 TI - Scintigraphic diagnosis of thyroid cancer. Correlation of thyroid scintigraphy and histopathology. AB - Scintigraphy is part of the routine examination of thyroid disease, yet there are few published reports on its utility and pitfalls. Out of 2025 consecutive thyroid examinations after excluding 230 cases of proven thyroid malignancies, 403 patients who underwent surgery were studied for histopathologic correlation. There were 232 with cold nodules, 143 with multinodular goiters (MNG) and 28 with uniformly increased uptake suggestive of toxic goiter. Malignancy was reported in 72 of the 232 cold nodules (31%). In solitary nodules, the examination was useful in selecting cases for surgery and, in cold lesions, for planning of surgery. In the majority of patients with MNG or thyrotoxicosis who were operated on, scintigraphy provided no additional information. MNG requires scintigraphy only in selected cases where there is strong suspicion of malignancy. Contrary to reports in the literature, papillary carcinoma was found to be associated with MNG in our patients. PMID- 8192957 TI - Conventional and high-resolution CT in asymptomatic asbestos-exposed workers. AB - To compare the value of conventional CT (CCT) and high-resolution CT (HRCT) to detect benign asbestos-related diseases, 159 exposed workers with a normal chest radiography were imaged by both techniques. Pleural plaques were detected in a total of 59 cases (37.1%). Ten cases (16.9%) were detected by CCT only and one case (1.7%) by HRCT only. Pulmonary lesions compatible with parenchymal asbestosis were detected by HRCT in 20 cases, whereas CCT showed abnormalities in 45% of these. Rounded atelectasis was equally recognized by both techniques. The results confirm that in a subject with a normal chest radiography, HRCT is a better diagnostic tool to demonstrate lesions of asbestosis. On the other hand, HRCT is insufficient to exclude the presence of pleural plaques. When HRCT does not reveal pleural abnormalities, CCT should be performed. PMID- 8192958 TI - CT and chest radiography in the evaluation of adult respiratory distress syndrome. AB - CT is seldom employed in adult respiratory distress syndrome (ARDS), mostly due to problems in transporting and monitoring these severely ill patients. We reviewed the findings of 74 ARDS patients who underwent chest CT. Lung opacities were bilateral in almost all patients and dependent in most cases (86%). The opacities were patchy (42%), homogeneous (23%), ground glass (8%) or mixed (27%). Opacities prevailed in basal regions (68%) compared to hilar and apical ones. Air bronchograms were frequently seen in areas of consolidation (89%). In contrast with previous reports, pleural effusion was a frequent finding (50%) that did not worsen prognosis. Often loculated pneumothorax (32%) was mostly anteromedial. Ineffective position of thoracostomy tubes was detected at CT in 13/20 patients. Pulmonary air cysts (30%), always multiple and mostly bilateral, were associated with a higher mortality (55%) than that of the whole study group (35%). Compared to chest radiographs, CT often yielded additional information (66%), with direct influence on patient treatment in 22% of cases. PMID- 8192959 TI - Quality assurance of the bedside chest radiography process. AB - The bedside chest radiography process was analyzed in terms of modern quality management guidelines and the sources of quality problems were identified. In order to analyze systematically the various quality factors, the process was described in a top-down fashion with the aid of data flow diagrams. Two internal quality control points and one external point were found in the process. Means to measure quality at the quality control points including questionnaires and a formula for calculating the internal quality index were developed. PMID- 8192960 TI - Improvement of bedside chest radiograph quality using a high ratio grid and an electronic angle meter for alignment. AB - An electronic level was used to ensure proper alignment of a high ratio grid at bedside chest radiography. The image quality was clearly improved. The method is inexpensive and simple to use. PMID- 8192961 TI - CT of saber-sheath trachea. Correlation with clinical, chest radiographic and functional findings. AB - The diagnosis of saber-sheath trachea is easy at CT due to its cross-sectional imaging, but the significance of this CT sign has not been evaluated in the diagnosis of chronic obstructive pulmonary disease (COPD). Various signs of COPD were compared between a series of 20 patients with a saber-sheath trachea at CT (tracheal index < or = 66%) and a group of 20 pneumologic control patients without saber-sheath trachea (tracheal index > or = 70%). These signs included clinical and standard radiographic indices of COPD, sternum-spine distance and 3 functional tests of COPD: forced expiratory volume in one second, carbon monoxide diffusing lung capacity, and functional residual capacity (FRC). A significant difference was found between the 2 groups, concerning the values of FRC (p < 10( 4)) and of sternum-spine distance (p < 10(-2)). The tracheal index was significantly correlated with the FRC values (r = -0.611; p < 10(-5)) and with the sternum-spine distance (r = -0.322; p < 0.05). No other significant difference was observed. It is concluded that saber-sheath trachea is basically a sign of hyperinflation. PMID- 8192962 TI - Diagnosis of diffuse lung disease by cutting needle biopsy. AB - The results of 15 consecutive automated cutting needle (1.2 mm, n = 14; 2.0 mm, n = 1) biopsies of diffuse lung manifestations are presented. Sufficient material for histologic analysis was obtained in 13 of 15 specimens (87%) and a specific diagnosis was obtained in 11 of 14 patients (79%). The tissue specimen confirmed the clinically probable lung disease in 6 patients, gave a new, unsuspected, diagnosis in 2, and resolved a differential diagnostic problem in 3 patients. One pneumothorax after a 2.0-mm needle biopsy necessitated catheter drainage. We conclude that percutaneous lung biopsy with the automated biopsy device mounted with a 1.2-mm needle yields a histologic diagnosis with high accuracy in interstitial and alveolar lung changes, reducing the need for more invasive methods such as open lung biopsy. PMID- 8192963 TI - Paraesophageal varices presenting as a retrocardiac mediastinal mass. A case report. AB - This report is a reminder that portal hypertension with paraesophageal varices can present as a retrocardiac mass on the chest radiograph. Schistosoma mansoni, the probable etiology in this case, causes periportal fibrosis and is the most common explanation for portal hypertension worldwide. Modern imaging techniques were most helpful in the diagnostic work-up, ultrasonography revealing pathognomonic hyperechoic periportal bands, and CT and MR imaging showing the extent of collaterals. PMID- 8192964 TI - Relaxation times of normal breast tissues. Changes with age and variations during the menstrual cycle. AB - The influence of age on the relaxation times of normal breast parenchyma and its surrounding fatty tissue were evaluated, and the variations during a normal menstrual cycle were analyzed using an ultra low field 0.02 T imager. Thirty-nine healthy volunteers aged 21 to 59 years were examined to determine T1 and T2 relaxation times, and 8 of these volunteers were studied once weekly during one menstrual cycle. The only significant trend was an increase in the T2 of breast parenchyma with increasing age. During the menstrual cycle there was a slight but insignificant (p = 0.10) increase in T1 of the breast parenchyma values during the latter half of the menstrual cycle, and a corresponding increase in T2 values between the 2nd and 3rd weeks of the menstrual cycle, which was significant (p = 0.003). PMID- 8192965 TI - MR imaging of edematous limbs in lymphatic and nonlymphatic edema. AB - MR imaging reflects the water content of various tissues. To evaluate the role of MR imaging in the diagnosis of edema, various types of edema were examined with MR imaging. MR imaging of edematous limbs was performed on 60 patients (lymphatic edema 48, nonlymphatic edema 12) using T1- and T2-weighted spin-echo and short inversion time inversion recovery sequences. Thickness and signal intensity of the cutis, subcutis and subfascia were evaluated in the images. In all 48 cases with lymphatic edema, trabecular structures suggesting dilated collateral lymphatic vessels were observed in the swollen subcutis. Two cases with nephrotic syndrome showed similar findings. In 6 cases with venous edema, fatty intensity was found in the subfascia. In the remaining 4 cases, the subcutis exhibited only water intensity. MR imaging is a potential contributor to the diagnosis of various edematous diseases. PMID- 8192966 TI - Angiography and colour flow duplex ultrasonography in the evaluation of peripheral ischaemic occlusive arterial disease. AB - Colour flow duplex ultrasonography (CFDUS) was performed in 50 patients with advanced peripheral ischaemic disease scheduled for conventional angiography. Atherosclerosis was diagnosed by the appearance of plaque and spectral broadening. Haemodynamically significant stenosis was represented as a doubling of peak systolic velocity expressed as peak velocity ratio. Occlusion was diagnosed by the lack of colour saturation and absence of Doppler wave form. In the pelvis and thigh/knee region the sensitivity and specificity exceeded 90% except for stenoses, where the sensitivity was lower. The run-off was evaluated by examination of the tibial and peroneal arteries to at least midcalf. If 2 open arteries were identified, or, if only the posterior tibial artery was patent, the run-off was considered good. Compared to angiography the sensitivity and specificity exceeded 90%. We conclude that CFDUS is an accurate non-invasive method for preoperative screening of patients with peripheral ischaemic disease. PMID- 8192968 TI - MR imaging of benign peripheral nerve sheath tumors. AB - In a retrospective, nonblind review of MR imaging of 15 benign peripheral nerve neoplasms in 13 patients, the signal pattern of the tumors (including contrast enhanced images) and stage were assessed. One lesion was subcutaneous, 9 intramuscular, 2 intermuscular and 3 extracompartmental. One lesion was located to the trunk, 5 to the upper extremity and 9 to the lower. The signal on T1 weighted spin-echo images was homogeneous isointense compared to adjacent muscle in 11 lesions and in 2 slightly hyper- and in 2 slightly hypointense. T2-weighted spin-echo images, acquired in all but one examination, showed a hyperintense signal, homogeneous in 8 and centrally inhomogeneous in 6 lesions. Postcontrast T1-weighted images of 11 lesions showed a strong signal, with an inhomogeneous enhancement in the center of the lesion similar to that obtained in T2-weighted images. In 2 cases there were signal characteristics indicating bleeding in the tumor. In one lesion both the nonenhanced and contrast-enhanced T1-weighted images showed a hypointense signal in the tumor center suggestive of intramuscular myxoma. All lesions were well delineated without reactive edema. In all cases, anatomic tumor location was correctly assessed. Although the findings were not pathognomonic for neurinoma, MR imaging provided valuable information confirming the clinical and cytologic assessments. PMID- 8192967 TI - Dynamic gadolinium-enhanced MR imaging in active and inactive immunoinflammatory gonarthritis. AB - Dynamic T1-weighted FLASH MR imaging, obtained just after i.v. gadopentetate dimeglumine injection, and pre- and postcontrast T1-weighted spin-echo (T1-SE) MR imaging were performed to compare their information value with respect to inflammatory activity in immunoinflammatory gonarthritis. We examined 16 clinically active (CAG), 7 clinically inactive (CIG) and 4 healthy knees. The synovium of a preselected slice was outlined. Its area and relative signal intensity increase after gadopentetate dimeglumine on T1-SE and FLASH (at each time t) were calculated. The CAG knees showed a mean signal intensity increase on early dynamic FLASH images higher by far than the CIG knees, while no significant difference was found on spin-echo images obtained 5 to 15 min after contrast injection. The early signal enhancement probably reflects the perfusion and capillary permeability of the synovium. The area of synovium could differentiate between healthy and arthritic knees. Gadolinium-enhanced dynamic FLASH imaging may provide clinically useful information about the actual inflammatory activity of arthritic joints. PMID- 8192969 TI - Assessment of rotation in proximal humeral osteotomy. AB - The correlation between the shift measured on bone surface in rotatory osteotomy and the radiologic change of the retroversion angle was analyzed. The humeral head retroversion was measured radiographically in 7 isolated humeri by means of a semiaxial projection. All bones were then osteotomized and the humeral head rotated in order to increase and decrease the retroversion. The retroversion was measured radiographically for each new rotational position of the head. The relationship between the measured shift in rotatory osteotomy and the change of retroversion was found to be linear. Twelve patients with recurrent anterior shoulder joint dislocations and a small humeral head retroversion were operated on in order to increase the retroversion. In all patients the increase of retroversion angle was smaller (57%) than expected on the basis of the shift in osteotomy and humeral diameter. The mean increase of retroversion was 2 degrees/mm shift (range 1.3-3.0 degrees/mm). PMID- 8192970 TI - Evaluation of spinal bone changes in patients with chronic renal failure by CT and MR imaging with pathologic correlation. AB - To investigate bone changes in patients with chronic renal failure (CRF), bone mineral density (BMD) and T1 relaxation times were measured with CT and MR imaging and the results were correlated to histology. Excised lumbar vertebrae from 25 autopsy cases of CRF (18 males and 7 females), including 12 cases in which the patients had been receiving hemodialysis were examined. BMD and T1 relaxation time values were associated with specific histologic findings for cellularity, trabeculae, and peritrabecular fibrosis. Three vertebrae with low BMD showed increased hematopoietic marrow content, a finding not observed in primary osteoporosis. The vertebrae with osteosclerosis showed prolonged T1 relaxation time, which was due to increased amount of hematopoietic marrow, and the presence of thickened or many small irregular trabeculae or peritrabecular fibrosis. These findings may be useful in the evaluation of bone changes in patients with CRF. PMID- 8192971 TI - Radiation exposure to children in diagnosing and at hydrostatic reduction of intussusception. AB - The energy imparted to the children in diagnosing and hydrostatic reduction of intussusception was measured in 45 children by means of an area-dose measurement device and the mean absorbed dose was estimated. The device was provided with data on tube kVp, mAs and shutter positions and the results were presented as dGy x cm2. The device had been calibrated against a 30 cm3 ionisation chamber at the relevant kVp range. The median energy imparted and mean absorbed dose were 10.8 mJ and 0.94 mGy, respectively. 70% of the total dose was delivered during fluoroscopy. The complex irradiation situation with varying field collimation, tube voltage and amount of photon absorbing barium sulphate in the intestines renders organ dose and hazards estimations less reliable. However, even leaving the radiation shielding effect of the barium sulphate out, the radiation load is justifiable for a combined diagnostic and interventional procedure. PMID- 8192972 TI - Digital rectal examination and transrectal ultrasonography in staging of rectal cancer. A prospective, blind study. AB - Staging of rectal carcinoma before surgical treatment was performed in a prospective blind study, comparing digital rectal exploration and transrectal linear ultrasonography (TRUS) with the resulting pathological examination. TRUS underestimated depth of penetration in 3 of 33 patients and overestimation resulted in 9 of 74. The figures for digital examination were 5 of 18 and 20 of 76, respectively. Penetration of the rectal wall was correctly identified in 56 of 61 patients by digital examination and in 59 of 61 by TRUS. Specimens without penetration of the rectal wall were identified in 26 of 33 patients by TRUS, but in not more than 13 of 33 by digital examination. Regional lymph node metastases were present in 19 patients; none were diagnosed by digital examination, but TRUS identified 11 of the 19. It is concluded that TRUS will result in more patients having the possibility of local surgery for cure. PMID- 8192973 TI - CT manifestations of intraspinal air associated with pneumomediastinum. AB - Collections of air in the spinal canal have been observed in patients with spinal disorders, whereas intraspinal air secondary to pneumomediastinum is rare (6). This is a report of 2 patients with pneumomediastinum where collections of air were identified in the spinal canal on CT. PMID- 8192974 TI - [Part time explodes--full time loses ground]. PMID- 8192975 TI - [Ahead with a fairer wage system. Interview by Kjell Arne Bakke]. PMID- 8192976 TI - [Point system decides wages. Interview by Kjell Arne Bakke]. PMID- 8192977 TI - [Nurses make good directors]. PMID- 8192978 TI - [An increase in operating room technicians]. PMID- 8192980 TI - [The right attitude--obscure medicine. Interview by Bjorn Arild Ostby]. PMID- 8192979 TI - [Beyond system. Interview by Siv Barstad]. PMID- 8192981 TI - [Need to evaluate 4-year education. Interview by Bjorn Arild Ostby]. PMID- 8192982 TI - [A better working day without anesthesia gases]. PMID- 8192983 TI - [More time for students]. PMID- 8192984 TI - ["Operated on for panic". Interview by Siv Barstad]. PMID- 8192985 TI - [Nursing under a different sky: Kindu]. PMID- 8192987 TI - [Valiant effort against AIDS]. PMID- 8192986 TI - [Nurses among the ruins of Lebanon. Interview by Anders Davidsen]. PMID- 8192988 TI - [Call for increased effort. 30 years expressed concern]. PMID- 8192989 TI - [Call for increased effort. Increased expectation pressure]. PMID- 8192990 TI - British Cardiac Society annual meeting. South Devon, 17-19 May 1994. Abstracts. PMID- 8192991 TI - Microproteinuria predicts the severity of systemic effects of reperfusion injury following infrarenal aortic aneurysm surgery. AB - Noncardiogenic pulmonary dysfunction can be demonstrated in all patients following elective aortic aneurysm repair and is a cause of postoperative morbidity. Aortic clamping and reperfusion initiate a systemic inflammatory response producing endothelial damage and increases in vascular permeability. In the lung this is manifest as pulmonary edema and in the kidney as detectable increases in urinary protein excretion (microproteinuria). Immunoassay of low level protein excretion appears to provide an index of the systemic effects of local reperfusion injury and may allow early prediction of complications such as pulmonary edema. Hourly urinary albumin and IgG excretion was measured in 40 patients undergoing infrarenal aortic aneurysm repair and expressed as ratios to urinary creatinine (albumin/creatinine ratio [ACR] and IgG/creatinine ratio [IgGCR]). These were compared to clinical outcome. Pulmonary dysfunction was assessed according to PaO2:FiO2 ratios and chest radiography. Within 180 minutes of beginning surgery all patients had significant increases in ACR and IgGCR. Ten patients who manifested respiratory dysfunction had significantly higher ACRs at 4 hours (median 84.8, 95% confidence intervals, range 47.7 to 136) than patients who made uneventful recoveries (median 16.6, 95% confidence intervals, range 7.9 to 31.7). IgGCR increases paralleled that of ACRs. Differences persisted for 24 hours. Urinary protein excretion rises rapidly during aortic surgery. The degree of increase appears to predict development of pulmonary dysfunction. This simple test may provide a rational basis for evaluation of therapeutic modalities to limit reperfusion injury in these patients. PMID- 8192992 TI - Morphology predicts rapid growth of small abdominal aortic aneurysms. AB - This study evaluated CT scans of small abdominal aortic aneurysms (AAAs) (< 5 cm) to assess anatomic features associated with rapid expansion. Serial CT scans obtained at least 10 months apart (mean 15 months) from patients with small AAAs were reviewed. Each cross-sectional image of the AAAs was analyzed using a computer-assisted design program. The circumference of the AAA in each CT image was divided into eight equal arcs, from which the apparent radius of curvature (Rc) for each segment was calculated. Flattening of the wall curvature results in an increased segmental Rc. The CT scans of nine patients with expanding AAAs (expansion > or = 0.5 cm/yr) were compared to those of 10 patients with stable AAAs (expansion < or = 0.2 cm/yr). To adjust for differences in AAA size, the Rc for each segment was normalized by dividing each individual Rc by the average of the eight Rcs (RcAvg) calculated for that cross-sectional CT image. Analysis of variance showed that the left posterolateral segments in expanding AAAs had larger Rc/RcAvg ratios than those segments in stable AAAs (1.14 +/- 0.19 vs. 0.80 +/- 0.09, p < 0.02). Laplace's law indicates that the left posterolateral segment in AAAs that grow more rapidly is subjected to greater wall tension. Flattening in the curvature of the left posterolateral wall segment was significantly associated with an increased rate of expansion in small AAAs. This finding, readily derived from standard CT scan images, may predict which small AAAs are more prone to rapid expansion. PMID- 8192993 TI - Infrainguinal revascularization in end-stage renal disease. AB - Patients with end-stage renal disease are being maintained for longer periods with dialysis or renal transplantation. Although renal failure itself is associated with occlusive peripheral vascular disease, such patients often have additional comorbid risk factors. In this series, 88% of patients were diabetic, 93% were hypertensive, and 44% were smokers, all factors that exacerbate the severity of their vasculopathy. As a consequence, the vascular surgeon is increasingly being confronted with limb-threatening peripheral vascular disease in this population. We performed 34 infrainguinal bypasses in 27 patients during a 8-year period from 1986 to 1993. Fifty percent of these were bypasses to the infrapopliteal level. The 12- and 48-month graft patency was 64% and 38%, respectively, by life-table analysis. The limb salvage rate was 65% and 58% at 12 and 48 months. The perioperative mortality rate was 5.9% and the morbidity rate was 37%. Most of the limb loss (66%) occurred during the first 3 months after surgery as a result of acute graft occlusion or nonhealing of an ulcer or minor amputation site. We believe that this reflects an increasingly aggressive approach to limb salvage in patients with end-stage renal disease. Four limbs were lost despite a patent graft. Infrainguinal bypass is a viable management option for limb salvage in patients with end-stage renal disease. These procedures can be undertaken with acceptable perioperative mortality and with a 12-month limb salvage rate of 65%. PMID- 8192994 TI - Primary aortoenteric fistula: Part I. PMID- 8192996 TI - Angioscopic evaluation of valvular disruption during in situ saphenous vein bypass. AB - Several valvulotomes are currently available to achieve valvular disruption; however, studies comparing the efficacy of these endoluminal instruments are lacking. This prospective study evaluates the efficacy and safety of the three most commonly employed valve cutters: the Hall, LeMaitre, and Mills valvulotomes. A total of 30 in situ greater saphenous vein bypass grafts were included in this investigation. Valvular disruption was attempted with either the LeMaitre (11 cases), Hall (12 cases), or Mills (7 cases) valvulotomes. Subsequently, angioscopy was employed to assess the completeness of valvulotomy and to identify vein wall injury. Incomplete disruption of one or more valve complexes was identified in 2 of 12 (17%) grafts in the Hall group, 10 of 11 (91%) grafts in the LeMaitre group, and 0 of 7 grafts in the Mills group (p < 0.01). Intact valve cusps were noted in 2 of 36 (5.5%) valves, 31 of 42 (74%) valves, and 0 of 38 valves after valvulotomy with the Hall, LeMaitre, and Mills instruments, respectively (p < 0.01). A total of three valvulotome-related injuries occurred; two injuries were noted in conjunction with the Hall instrument, one was associated with the Mills valvulotome, and no injuries were detected after use of the LeMaitre instrument (p = 0.33). These data demonstrated a significantly increased incidence of retained valve cusps when the LeMaitre valvulotome was used. No significant difference in the rate of vein wall injury was noted in the three groups. Thus this study suggests that the LeMaitre instrument is not as effective as either the Hall or Mills valvulotomes for achieving valvular disruption. PMID- 8192995 TI - Popliteal artery aneurysms: the risk of nonoperative management. AB - To evaluate the risk of nonoperative management of popliteal artery aneurysms (PAAs), a retrospective cohort study of 106 consecutive patients (103 males and 3 females) with PAAs seen between January 1, 1980, and December 31, 1985, was performed. The mean age was 70.5 years (range 50 to 90 years). The 106 patients with 161 PAAs were followed for a mean of 6.7 years (range 3 days to 12.1 years). Follow-up was complete in 91.5% (97/106) of the patients. PAA was confirmed by ultrasonography in 124 limbs (77%), arteriography only in 7 (4.3%), and physical examination only in 32 (19.9%). Fifteen limbs presented with acute symptoms, 52 with chronic symptoms, and 94 were asymptomatic. Five of the 15 limbs with acute symptoms (33%) underwent amputation (4 primary, 1 secondary). PAAs in 23 of the 52 limbs with chronic symptoms were repaired; 2 limbs required amputation (8.7%). Twenty-seven of the 94 asymptomatic limbs were repaired initially; 1 required amputation (3.7%). The remaining 67 asymptomatic limbs were initially managed nonoperatively. Amputation was required in 3 of 67 limbs (4.4%), 1 with acute symptoms and 2 with chronic symptoms, all of which had undergone attempted repair. Symptoms (3 acute, 9 chronic) eventually developed in 12 (17.9%). At least one of three risk factors (size > 2 cm, thrombus, and poor runoff) was initially present in 11 of 12 limbs (91.7%) compared with 9 of 24 control limbs (37.5%) that remained asymptomatic (p < 0.05). Amputation rates in symptomatic patients with PAAs continues to be high. In patients with asymptomatic PAAs, aneurysm size > 2 cm, thrombus, or poor runoff predicted the development of symptoms. PAA patients with any of these factors should undergo elective repair, even asymptomatic patients who have a reasonable chance for long-term survival. PMID- 8192997 TI - Comparison of muscle flaps and delayed secondary intention wound healing for infected lower extremity arterial grafts. AB - Selective preservation of infected arterial grafts is an alternative to graft excision. The purpose of this study was to compare the outcome and cost of treating infected lower extremity arterial grafts with either muscle flaps (MFs) or delayed secondary intention (DSI) wound healing. Between 1985 and 1991 we treated 28 graft infections by graft preservation. All grafts (19 polytetrafluoroethylene, 8 autologous vein, and 1 Dacron) were patent with intact anastomoses and showed no signs of sepsis. Wounds in 18 patients were treated by repeated, aggressive operative debridement and allowed to heal by DSI. Wounds in 10 patients were treated with MFs (4 sartorius, 3 gracilis, 1 rectus abdominis, 1 semimembranous, and 1 gastrocnemius). Costs included anesthesiologists' and surgeons' fees, operating room charges, and daily semiprivate and ICU bed charges. Four (14%) patients died from cardiac complications (1 DSI and 1 MF), sepsis (1 MF), and anastomotic hemorrhage (1 DSI). Of the 24 survivors, 4 patients treated by DSI required graft excision for nonhealing wounds (2), graft thrombosis (1), and recurrent infection (1). However, 3 of these 4 patients were not candidates for MFs because the wounds were not considered acceptable for a flap. Twenty (83%) grafts in survivors were successfully preserved after long term follow-up (mean 26 mo). No survivors required an amputation. Twenty patients who did not require graft removal were compared for treatment by MF (n = 8) or DSI (n = 12). Two MFs (both sartorius) in survivors necrosed and a new flap was required to successfully preserve the graft.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8192998 TI - Use of the descending thoracic aorta as an inflow source in aortoiliac reconstruction: indications and long-term results. AB - Bypass grafting from the descending thoracic aorta to the iliac or femoral artery is an underutilized procedure; fewer than 200 cases were reported in the past 30 years. Over the last decade we performed 32 bypasses to the femoral iliac or popliteal arteries using the descending thoracic aorta as the inflow source. In 19 (59%) patients the procedure was a primary aortic reconstruction, whereas in 13 (41%) it was secondary. The 30-day in-hospital mortality rate was 6.2%. Primary graft patency was 86% (+/- 7.8) at 2 years. To obtain a meaningful long term patency analysis, we combined our experience with that reported in the literature during the same period. Follow-up data were available in 146 patients in whom the mean follow-up time ranged from 15 to 53 months. The operation was a secondary aortic reconstruction in 84 (58%) patients and was a primary procedure in 62 (42%). Reasons for the selection of the descending thoracic aorta as the inflow source included previous abdominal aortic graft failure in 56 (38%) patients, abdominal aortic graft infection in 26 (18%), unfavorable abdominal conditions in 30 (21%), and miscellaneous causes in 34 (23%). The 30-day in hospital mortality rate for the collective experience was 5.5%. Life-table analysis of the collective primary graft patency rate was 88.3% (+/- 2.9) at 1 year, 81% (+/- 4.3) at 3 years, and 72.7% (+/- 8.5) at 6 years. Secondary graft patency for the collective experience was 93.1% (+/- 2.3) at 1 year, 88.2% (+/- 3.7) at 3 years, 82.7% (+/- 7.3) at 6 years, and 82.7% (+/- 10) at 8 years. Patient survival was 67.5% (+/- 6.9) at 5 years and 55.4% (+/- 9.9) at 7 years. These data suggest that bypass from the descending thoracic aorta to the iliac or femoral arteries offers low mortality and excellent durability and should be considered as the procedure of choice for secondary or extra-anatomic aortoiliac reconstruction. PMID- 8192999 TI - Percutaneous transluminal angioplasty of tibial arteries for limb salvage in the high-risk diabetic patient. AB - Recent advances in balloon catheter technology allow percutaneous transluminal angioplasty (PTA) of small arteries such as the tibial arteries. PTA can thus be used to treat lower limb ischemia in diabetic patients whose arterial occlusive disease is often localized to the tibial arteries. This series included 14 consecutive diabetic patients who underwent tibial PTA for treatment of limb threatening ischemia from 1986 to 1992. PTA was selected over conventional bypass procedures because of a lack of autogenous conduit or because of an unacceptably high surgical risk. Limb loss was imminent without prompt improvement in foot perfusion in all patients. Mean follow-up of 17 months demonstrated long-term limb salvage in 10/13 (77%) and "late" cardiac-related death in 3/13 (23%). This series demonstrates that although conventional arterial bypass should routinely supersede angioplasty procedures, tibial PTA offers the opportunity for limb salvage in diabetic patients with inadequate autogenous conduit for distal tibial bypass and may serve as an option for those who are considered too high risk for conventional bypass. Morbidity and mortality rates of tibial PTA parallel those of major amputation in this population with the obvious benefit of achieving limb salvage in carefully selected diabetic patients. PMID- 8193000 TI - Benefits of carotid patching: a prospective randomized study with long-term follow-up. AB - A prospective study with random selection between primary closure and saphenous vein patching after carotid endarterectomy was conducted. Patients were evaluated with intravenous digital subtraction angiography during the initial postoperative period, followed by duplex scanning at 3 and 6 months, and then yearly examinations. The series consisted of 129 carotid endarterectomies, of which 62 were primary closures and 67 were patch procedures. Both groups were identical with regard to risk factors, symptoms, and postoperative control digital subtraction angiography. Restenosis was defined as a stenosis with > or = 50% diameter reduction, as assessed by duplex scanning. Of special interest was the development of restenosis along with the occurrence of cerebrovascular symptoms at long-term follow-up. The follow-up data from the 129 carotid endarterectomies are presented in a life-table analysis. The mean length of follow-up was 5 years (range 1 to 96 months). During the follow-up period 38 patients who had undergone 39 operations died (mortality rate 30%); three deaths were attributed to cerebral causes (two in-hospital deaths due to intracerebral hemorrhage and one cerebral hemorrhage after 6 months). Restenosis occurred in 25 cases (19%). This restenosis was detected in 5 of 45 men with primary closure (11%), 12 of 17 women with primary closure (70%), 7 of 49 men with patch closure (14%), and 1 of 18 women with patch closure (5.5%). The difference between patch and primary closures was found to be statistically significant (hazard ratio 0.39; 95% confidence interval 0.17 to 0.91; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193001 TI - Thrombolysis in acute peripheral arterial occlusion: predictors of immediate success. AB - Thrombolytic therapy is frequently used for the treatment of peripheral arterial occlusion, but clinical predictors of success have not yet been defined. We prospectively evaluated 80 consecutive patients receiving intra-arterial urokinase for acute (< 14 days) ischemia. Fifty-five patients (69%) were treated for bypass graft occlusion and 25 patients (31%) for native arterial occlusion. Two primary outcome measures were evaluated using multivariate techniques (stepwise logistic regression) to determine the independent predictors of immediate arteriographic success: successful (> 80%) thrombolysis and avoidance of adjuvant operative or endovascular procedures. Independent variables examined included age, sex, comorbid conditions, severity, duration, etiology and location of the ischemic process, and positioning of the infusion catheter and guidewire. Overall, successful lysis was achieved in 57 patients (71%) and adjuvant procedures were avoided in 22 patients (28%). Successful outcome was more frequent in prosthetic graft (78%) and native arterial (72%) occlusions than in vein graft occlusions (53%, p = 0.017) and in nondiabetics than in diabetics (80% vs. 52%, p = 0.031). Lysis was dependent on placement of the catheter into the substance of the thrombus (85% vs. 0% success, p = 0.004) and passage of a guidewire through the occlusive process (92% vs. 10% success, p = 0.001). The only parameter independently predictive of successful outcome without the use of adjuvant procedures was the location of the occlusion; additional procedures were necessary in 88% of aortoiliac and 82% of infrainguinal occlusions vs. only 17% of upper extremity occlusions (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193002 TI - Hypothermia and bleeding during abdominal aortic aneurysm repair. AB - Patients undergoing abdominal aortic aneurysm repair routinely have a depressed core body temperature during surgery, and hypothermia is known to cause abnormalities in coagulation. This study was designed to determine whether platelet function is altered as a result of hypothermia or heparin during abdominal aortic aneurysm repair. Ten patients scheduled for abdominal aortic aneurysm surgery were prospectively studied. Bleeding times and temperature were measured every hour beginning preoperatively. Each patient was heparinized intraoperatively, and the effects reversed with protamine sulfate prior to closure. Despite efforts to keep the patients warm, all of them developed hypothermia (mean lowest core temperature 34.8 +/- 0.7 degrees C). A significant linear relationship between the change in core temperature and the change in bleeding time was demonstrated. In 7 of 10 cases the greatest change in bleeding time occurred when patients experienced the lowest mean core temperature and not when they were heparinized. These data suggest that hypothermia has a marked effect on platelet function during abdominal aortic aneurysm repair. Although heparin can cause abnormalities in platelet function, hypothermia may be a more important role in inhibiting normal platelet function. By preventing severe hypothermia (< 35 degree C), excessive bleeding associated with abdominal aortic aneurysm repair may be minimized without the concomitant risk of blood product transfusion. PMID- 8193003 TI - Continuous postoperative intra-arterial urokinase infusion in the treatment of no reflow following revascularization of the acutely ischemic limb. AB - The loss of distal tissue perfusion sufficient for limb salvage following restoration of inflow to an acutely ischemic extremity has been referred to as the "no-reflow" phenomenon. We hypothesized that patients with no reflow and limb threat ischemia might benefit from prolonged postoperative intra-arterial infusion of the thrombolytic agent urokinase (UK). Twelve patients with arteriographic and clinical evidence of no reflow following a lower extremity arterial thrombectomy and/or bypass procedure were treated with a continuous intra-arterial UK infusion in the immediate postoperative period. The mean duration of UK infusion was 47 hours (range 15 to 112 hours). The mean rate of infusion was 58,000 units/hr (range 30,000 to 100,000 units/hr). Seven patients required transfusion for bleeding from the treated extremity (mean 3.4 units packed cells) and one required reoperation for a groin hematoma. Plasma fibrinogen levels remained within the normal range in all patients, and no systemic bleeding complications were encountered. The intra-arterial UK infusion resulted in limb salvage in 7 of 12 patients. Six patients have viable, functional extremities at a mean follow-up interval of 24.9 months (range 6.4 to 49.7 months). One patient required below-knee amputation 6 months after treatment for progressive ischemia. The other five patients required below-knee amputation during the same hospitalization after UK failed to restore distal perfusion. The postoperative period is widely considered to be a contraindication to thrombolytic therapy. Our experience indicates that while UK may cause bleeding from the treated extremity, which in some cases requires transfusion, there is no evidence of systemic fibrinolysis or systemic hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193004 TI - Role of angioscopy in reoperation for the failing or failed infrainguinal vein bypass graft. AB - The purpose of this retrospective study is to review our ongoing experience with the use of angioscopy during reoperation for failed or failing infrainguinal vein bypass grafts and define the role of angioscopy in the management of this clinically demanding patient group. All hospital records, arteriograms, and intraoperative angioscopic video recordings of 79 consecutive failed or failing grafts (76 patients) examined with angioscopy during reoperation between 1987 and 1993 were reviewed. Clinical and intraoperative data, comparison of the preoperative arteriogram and intraoperative angioscopic findings, and surgical decisions or interventions resulting from the additional angioscopic findings were collated and analyzed according to a predetermined protocol. Sixty-six additional angioscopic findings were noted during the 79 reoperations and resulted in 61 additional interventions and surgical decisions with salvage of all or part of the graft in 90.9% in the early (< 30 day) failed (group 1), 84.6% in the late (> 30 day) failed (group 2), and 90.3% in the late (> 30 day) failing grafts (group 3). The amount of residual thrombus within the graft, as assessed by angioscopy after all interventions, was the critical determinant for overall early graft patency (p < 0.001) and long-term patency for all the subgroups after reoperation (group 1, p < 0.001; group 2, p = 0.0016; and group 3, p = 0.0194). Intraoperative angioscopy has an important role in these challenging procedures. It provides additional and useful information that not only influences the conduct and extent of the reoperative surgery but may provide insights into the pathogenesis of graft failure. PMID- 8193005 TI - Does arterial inflow failure cause distal vein graft thrombosis? A prospective analysis of 450 infrainguinal vascular reconstructions. AB - Classically, inadequate arterial inflow, diseased runoff, and poor bypass conduit quality have all been cited as causes of infrainguinal vein graft failure. To examine the role of arterial inflow failure as a specific cause of vein graft thrombosis, we prospectively analyzed 450 consecutive infrainguinal vascular reconstructions by means of a strict duplex scan surveillance protocol at three teaching institutions from 1986 to 1993. Sixteen incidences of arterial inflow failure (11 occlusions and five high-grade stenoses) above previously placed infrainguinal vein grafts were identified in 14 patients and confirmed by arteriography. Despite these inflow failures, all 14 autogenous vein infrainguinal reconstructions remained patent on arteriography. These inflow failures were observed from 2 to 72 months (mean 16 months) after infrainguinal reconstruction. Immediate successful inflow repair was performed in 13 of the 16 failures. Conversely, among 450 grafts followed, 37 acute graft occlusions occurred-all with arteriographically or noninvasively documented normal inflow. Thus no graft in the series has yet failed as a result of inflow occlusion (mean follow-up 22 months; range 1 to 78 months). We thus conclude that properly constructed infrainguinal saphenous vein bypass grafts with an intact endothelium often remain patent through low-flow collateral vessels despite total arterial inflow occlusion. These data thus challenge the premise that arterial inflow disease is a major cause of infrainguinal vein bypass occlusion. PMID- 8193006 TI - Wound healing in forefoot amputations: the predictive value of toe pressure. AB - A retrospective study of 136 men undergoing forefoot amputation was done to test the hypothesis that preoperative toe pressure (TP) could predict the likelihood of wound healing. Demographic data included age, smoking history, diabetes mellitus (DM), hypertension, hyperlipidemia, and coronary artery disease. Clinical data included infection, preoperative arterial Doppler data, TP, wound disposition, concomitant revascularization (REV), and healing outcome. Among diabetics, no primary amputation healed with a preoperative TP < 38 mm Hg. Among REV diabetics, no healing occurred with a TP < 40 mm Hg after bypass, but no failures occurred either with a TP > 68 mm Hg or an increase in TP > or = 30 mm Hg after bypass. Nondiabetic patients exhibited no threshold TP values. Univariate analysis revealed that DM and REV were significantly different in the healed (N = 83) vs. nonhealed (N = 53) populations (p = 0.027 and 0.034). In healed patients mean TP (71.8 +/- 3.5 mm Hg SEM) was significantly higher than in nonhealed patients (45.1 +/- 4.3 mm Hg SEM, p = 0.000). Logistic regression analysis identified age > 60 years (p = 0.03), DM (p = 0.003), preoperative TP (p < 0.001), and REV (p < 0.001) as significant independent predictors of forefoot amputation healing. Healing probability was calculated and plotted vs. TP for subpopulations based on age, DM, and REV status for both primary forefoot amputation and amputation concomitant with bypass. In this study population, therefore, preoperative TP appeared to be a useful clinical tool for predicting the healing potential of both primary forefoot amputations and amputations plus concomitant bypass for any given patient. PMID- 8193007 TI - Global programme on AIDS. A study on the effect of blood transfusion on survival among children in a Kenyan hospital. PMID- 8193008 TI - Dracunculiasis eradication. Update: Mali and Niger, 1993. PMID- 8193009 TI - Tuberculosis in the Caribbean 1983-1992. PMID- 8193010 TI - Rift Valley fever. PMID- 8193011 TI - Tuberculosis. PMID- 8193012 TI - Human rabies. New York, 1993. PMID- 8193013 TI - Yellow fever virus surveillance in Western Africa. PMID- 8193014 TI - Resurgence of pertussis. 1993. PMID- 8193015 TI - Ross River virus infection. PMID- 8193017 TI - [Conservative treatment of chronic kidney failure]. PMID- 8193016 TI - [Care of a child with hemolytic-uremic syndrome]. PMID- 8193018 TI - [Dialysis and other blood purifying measures in acute and terminal kidney failure in children]. PMID- 8193019 TI - [Care of patients in peritoneal dialysis]. PMID- 8193020 TI - [Kidney transplantation in children]. PMID- 8193021 TI - [Care of a child following kidney transplantation]. PMID- 8193022 TI - [The pediatric nurse as a coworker in the pediatric nephrologic team]. PMID- 8193023 TI - [Psychosocial care of children with chronic kidney disease]. PMID- 8193024 TI - [Euthanasia--even a hopeless prognosis does not justify controlled killing]. PMID- 8193025 TI - [Pediatrician's practice--another field for pediatric nurses]. PMID- 8193026 TI - [Neurodermititis]. PMID- 8193027 TI - [Epidemiological aspects of sudden infant death]. PMID- 8193028 TI - [Visit to Oxford]. PMID- 8193029 TI - [Congenital malformations of the kidneys and the deferrent urinary tract]. PMID- 8193030 TI - [Prenatal diagnosis of congenital kidney and urinary tract malformations]. PMID- 8193031 TI - [Postnatal sonographic diagnosis of urinary tract malformations]. PMID- 8193032 TI - [Congenital malformations of the urinary tract--a central challenge in pediatric urology]. PMID- 8193033 TI - [Nursing of a newborn with bladder exstrophy]. PMID- 8193034 TI - [Kidney function testing and kidney function in the newborn]. PMID- 8193035 TI - [Acute kidney failure in the newborn]. PMID- 8193036 TI - [Care of a premature infant in indomethacin therapy with an open ductus arteriosus]. PMID- 8193037 TI - [Acute dialysis at the neonatal intensive care unit]. PMID- 8193038 TI - [Diagnosis and therapy of urinary tract infections in children]. PMID- 8193039 TI - [Urological aspects of urinary tract infections and urination disorders in children]. PMID- 8193041 TI - [Enuresis--from a pediatric viewpoint]. PMID- 8193040 TI - [Prevention of nosocomial urinary tract infections]. PMID- 8193042 TI - [Enuresis from the viewpoint of child psychiatry]. PMID- 8193043 TI - [Glomerulonephritis]. PMID- 8193044 TI - [Nephrotic syndrome in children]. PMID- 8193045 TI - [Kidney biopsy]. PMID- 8193046 TI - [Hemolytic-uremic syndrome]. PMID- 8193047 TI - [Surfactant substitution in respiratory distress syndrome of the premature]. PMID- 8193048 TI - [Nursing aspects of surfactant therapy]. PMID- 8193049 TI - [Chronic constipation]. PMID- 8193050 TI - [Poisonous and less poisonous plants]. PMID- 8193051 TI - [Care and guidance of constipated children]. PMID- 8193052 TI - [A good method: practice mentoring--experiences, problems, solutions]. PMID- 8193053 TI - Emotional attachments in abusive relationships: a test of traumatic bonding theory. AB - An empirical test of traumatic bonding theory, the notion that strong emotional attachments are formed by intermittent abuse, is reported. In-depth assessments (interviews plus questionnaires) were conducted on 75 women who had recently left abusive relationships (50 where physical violence had occurred). The study found support for the effect of relationship dynamic factors such as extremity of intermittent maltreatment and power differentials on long-term felt attachment for a former partner, experienced trauma symptoms, and self-esteem, immediately after separation from an abusive partner and again after a six month interim. All three of these measures were significantly intercorrelated within each time period. Each measure at Time 1 correlated significantly with each corresponding measure at Time 2. After six months attachment had decreased by about 27%. Relationship variables (total abuse, intermittency of abuse and power differentials) accounted for 55% of the variance in the attachment measure at Time 2 indicating prolonged effects of abuse suffered in the relationship. PMID- 8193054 TI - Victim-offender relationship and sexual assault. AB - The effect of the victim-offender sexual assault relationship on women's psychological symptomatology was examined in a randomized community survey. Fourteen and one-half percent of women (N = 240) experienced a sexual assault in adulthood. Assaults committed by strangers, acquaintances, and intimates were compared using both chi-square and two-way analyses of variance. Few differences were found in sexual assault experiences according to the victim-offender relationship. Offender use of violence showed a curvilinear relationship with degree of closeness of the victim-offender relationship, whereas victim resistance did not vary according to the victim-offender relationship. Analyses of psychological symptom measures showed that sexual distress was more common for women attacked by intimates, fear/anxiety was more common for women assaulted by strangers and depression did not vary according to the victim-offender relationship. PMID- 8193055 TI - A comparison of adaptive strategies and patterns of victimization among homeless adolescents and adults. AB - One hundred and fifty-six homeless adolescents and 319 homeless adults interviewed directly on the streets and in shelters were compared for backgrounds of abuse, adaptations to life on the streets, and rates of criminal victimization when on the streets. Homeless adolescents were more likely to be from abusive family backgrounds, more likely to rely on deviant survival strategies, and more likely to be criminally victimized. A social learning model of adaptation and victimization on the streets was hypothesized. Although the model was supported for both homeless adults and adolescents, it was more strongly supported for adolescents than adults, and for males than females regardless of age. PMID- 8193056 TI - Sexual victimization in young, pregnant and parenting, African-American women: psychological and social outcomes. AB - The influence of sexual victimization on the psychological and social adjustment of 177 pregnant and parenting African Americans was examined. Compared with those who had not been victimized, young women with a history of sexual victimization were more symptomatic, had lower self esteem, and had a more external locus of control than the non-victimized women. In addition, women who were sexually victimized at some time in their lives reported higher levels of economic strain. Victimized young women were less satisfied with their social support than their non-victimized peers. Taken together, these findings suggest that the link between sexual victimization and psychological distress in pregnant and parenting adolescents may be mediated through young women's interpersonal resources. PMID- 8193057 TI - Family of origin violence and MCMI-II psychopathology among partner assaultive men. AB - This study examined associations between family of origin violence, self-reports of psychopathology on the MCMI-II, and current spouse abuse among partner assaultive men. Compared to nonviolent men in discordant (n = 24) and well adjusted (n = 24) relationships, partner assaultive men (n = 24) were significantly more likely to report childhood histories of physical abuse and physical abuse of the mother in the family of origin. The partner assaultive men also reported significantly higher scores on a variety of MCMI-II personality disorder and Axis I disorder scales. When negative affectivity was controlled, however, batterers differed from contrast groups only on scales assessing antisocial and aggressive characteristics. Within the partner assaultive group, a history of severe childhood abuse was associated with higher scores on a variety of MCMI-II personality disorder and Axis I disorder scales, and higher levels of psychological and physical aggression directed toward the current relationship partner. Abuse of the mother in the family of origin among batterers was associated with higher levels of psychological and physical aggression toward the current partner, but not with self-reported psychopathology. The results support prior descriptions of a batterer subgroup with significant trauma histories, more psychological difficulties, and higher abuse levels than other batterers, suggesting continuities in social and emotional development from childhood maltreatment to adult relationship violence. PMID- 8193058 TI - Juror stress. AB - That jurors may be harmed as a result of their carrying out their civic duties is receiving increased attention from the courts and the media (Sevilla & Beyers, 1990; Craver, 1993). The pilot tests reported here represent initial efforts to undertake a proactive project for identifying and mitigating the possible adverse effects of stress on jurors and to contribute to the understanding and treatment of secondary trauma for at-risk groups. In many ways juries are the black box of the legal system. Their decision-making process is typically shrouded in mystery. So that they may fully explore the issues and examine their consciences, jurors meet privately when reaching their decision and, beyond entering a verdict, are typically not required to provide the rationale for their verdict. Furthermore, jurors are often reluctant to discuss the bases for their verdicts after the trial is over and an unspoken code of honor may limit their willingness to critique their fellow jurors. Perhaps in part because we know so little about their decision-making process, as well as because of their intrinsic and symbolic importance to the legal system, there may be a tendency to take jurors for granted and to assume that they are relatively unaffected by their jury duties. Although jurors are expected to appear impassive and emotionally detached in court, for some trials it is only the rare individual who will not be emotionally moved by what he or she has seen and heard or by the gravity of the decision that is required. Several recent cases have provided a glimpse of what goes on within this black box and suggest that greater attention may need to be given to the needs of these jurors. PMID- 8193059 TI - Sexual aggression by an acquaintance: methods of coping and later psychological adjustment. AB - The main purpose of the present study was to determine if methods of coping with sexual aggression by acquaintances were associated with psychological adjustment beyond what could be predicted by characteristics of the attack itself and beyond what could be predicted by methods of coping used to deal with other stressors. Out of 401 undergraduate women respondents (mean age = 19), 106 or 26% had been victims of sexual aggression by an acquaintance since the age of 16. Two years on average after the assault, these women reported more psychological problems on the Brief Symptom Inventory (Derogatis & Spencer, 1982) than a comparison group who had not been assaulted since age 16. Respondents who had survived sexual aggression were asked to indicate on the Coping Strategies Inventory the methods they had used to cope with this experience and the methods they had used to cope with a separate nonsexual stressful event which also had occurred since age 16. Multiple regression analyses indicated that disengagement methods of coping with sexual aggression per se accounted for unique variance in general psychological distress as measured by the Global Severity Index of the Brief Symptom Inventory and in posttraumatic stress disorder symptoms as measured by a DSM-III-R derived checklist. PMID- 8193061 TI - Medial temporal lobe structures in schizophrenia: relationship of size to duration of illness. AB - Reductions in the size of medial temporal lobe structures in schizophrenia have been demonstrated using magnetic resonance imaging. It is not clear whether these neuropathological changes are present premorbidly or if they reflect an adult onset progressive process. In this study, quantitative measures were made of the lateral ventricles, third ventricle, amygdala, hippocampus, and cerebral hemispheres from coronal MRI images on 33 patients with schizophrenia and 41 normal controls. Images were selected a priori from the region of the temporal lobe in which we had previously demonstrated reduced volume of temporal lobe gray matter in a separate sample of patients. Results showed a decrease in amygdala, hippocampal, and amygdala-hippocampal size bilaterally and an increase in third and lateral ventricular volume. Advancing age in normals was associated with a decrease in the size of medial temporal structures and an increase in lateral ventricular size. In schizophrenia, there was a correlation between age and lateral ventricle size, but duration of illness was not associated with reductions in medial temporal tissue or ventricular enlargement. These results are consistent with prior evidence from neuroimaging and postmortem studies of medial temporal pathology in schizophrenia and support hypotheses that neuropathological changes in schizophrenia are not progressive. PMID- 8193060 TI - Red blood cell membrane dynamics in schizophrenia. I. Membrane fluidity. AB - Using the fluorescent probe DPH (1,6-diphenyl-1,3,5-hexatriene), steady-state anisotropy (rs) values were determined in red blood cell (RBC) ghost membranes of schizophrenic patients before (n = 26) and after (n = 16) haloperidol withdrawal, and age- and sex-matched normal controls (n = 22). Patients on haloperidol were treated with doses between 5 and 20 mg/day for at least 5 weeks. Drug-free patients had been free of all psychotropic medication for an average of 36 days. The mean rs value of haloperidol-treated patients (0.2422 +/- 0.0076) was not significantly different from that of either the drug-free patients (0.2445 +/- 0.0092) or the normal controls (0.2383 +/- 0.0083). A significant increase (p = 0.037) in rs values, however, was observed in the drug-free schizophrenic patients as compared to that of the controls. Furthermore, the mean rs values of relapsed drug-free patients were significantly (p < 0.05) higher than in the same individuals on haloperidol treatment. Changes in rs values of drug-free patients were also significantly correlated with their increase in psychosis ratings (r = 0.74, p = 0.001). The 'structural order' of RBC ghost membrane, however, was not correlated with age, age of onset, daily haloperidol dose, plasma haloperidol levels, plasma cholesterol concentrations, or the duration of illness, haloperidol treatment or drug-free period. Thus, the present data demonstrate that RBC membrane fluidity is not affected by haloperidol treatment. Following haloperidol withdrawal, however, those patients with decreased RBC membrane fluidity, which correlated with increased psychosis, may be prone to relapse within 6 weeks. PMID- 8193062 TI - Specificity of the Calgary Depression Scale for schizophrenics. AB - This study sought to determine the specificity of the Calgary Depression Scale (CDS), a depression rating scale for schizophrenics. The specificity is the degree to which the scale assesses depression rather than negative or extrapyramidal symptoms. Subjects were 100 outpatients (OP) and 50 inpatients (IP) meeting DSM-III-R criteria for schizophrenia. Negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS); extrapyramidal symptoms were assessed with the Simpson Angus Scale (SA) and depression with the CDS. Results were that the CDS showed no correlation with SA, but weak (0.33) statistically significant correlations with the PANSS negative symptom score in inpatients but not outpatients. Confirmatory factor analysis using Lisrel 6.0 showed that the model hypothesizing specificity of depression, negative symptoms and extrapyramidal symptoms, was significant, with a goodness of fit index of 0.89 and a root mean square residual of 0.07. It is concluded that the CDS achieves a useful degree of separation between measures of depression, negative and extrapyramidal symptoms in subjects with schizophrenia, when combined with the other measures used in this study. PMID- 8193063 TI - Brain structure changes in schizophrenics with high serum titers of antibodies to herpes virus. AB - We compared five indices of brain structure between two groups of schizophrenics, namely, those with high and normal levels of antibody in the serum to herpes virus. Eleven 'immuno-positive' and 21 'immuno-normal' subjects obtained from a concomitant study of serum IgG antibody to viruses underwent magnetic resonance imaging (MRI) utilizing a 1 Tesla magnet and 8 mm thick slices. We measured ventricle-brain ratio (VBR), 3rd ventricle width, cortical atrophy, area of corpus callosum, and frontal lobe area. The differences between groups were assessed by t-test and chi-square analysis. Eight of 11 immuno-positives compared to 7 of 21 immuno-normals showed evidence of cortical atrophy (chi 2 = 4.49, p < 0.03). The immuno-positives had smaller left frontal area (mean + s.d = 125.69 + 21.30 versus 143.76 + 19.84, t = 2.07, p < 0.05) and larger 2nd quadrant of the corpus callosum (mean + s.d. = 1.58 + 0.39 versus 1.27 + 0.52, t = 2.68, p < 0.01). The right frontal area also was smaller in immuno-positives but not significant. VBR, 3rd ventricle and the 1st, 3rd and 4th callosal quadrants did not differ between the groups. We conclude that high antibody titers to herpes found in the sera of some schizophrenics might reflect an earlier pathogenetic process that affected brain development. Further studies of antibodies in CSF and brain structure in these or similar subjects and those suspected to be exposed to viral infections in utero should be vigorously pursued to obtain definitive evidence for this hypothesis. PMID- 8193064 TI - Social anxiety in schizophrenia. AB - The relationship between social anxiety and positive and negative symptomatology in schizophrenia was investigated. Thirty eight inpatients with schizophrenia completed a battery of self-report measures of anxiety, a modified Stroop task, and an unstructured role play. Positive symptoms were related to fear in a number of self-report domains (i.e., social and agoraphobic). Negative symptoms were related to global observational ratings of anxiety during the role play as well as specific behaviors associated with self-reported social anxiety (i.e., speech rate and fluency). Positive symptoms generally were not associated with role play ratings. Thus, specific behaviors related to social anxiety appear to be associated with negative symptoms, while self-report is associated with positive symptoms. Problems in the assessment of social anxiety in individuals with schizophrenia and implications of these findings for social skills training in this population are discussed. PMID- 8193065 TI - The influence of parental socioeconomic status on CT studies of schizophrenia. AB - A sample of 19 DSM-III-R schizophrenics and 94 controls with no mental illness from the Copenhagen high-risk project was used to test the hypothesis that social class of origin is related to adult CT measures of ventricular, sulcal, Sylvian fissure and anterior interhemispheric fissure enlargement, cerebellar pathology, and brain volume. The schizophrenics and controls were divided into high and low SES-of-origin. No significant differences emerged between the high and low SES-of origin subjects within the schizophrenic and control groups on any of the six CT measures. PMID- 8193067 TI - Anatomy of the terminal nerves in the upper eyelid. AB - Anatomic dissections on human cadaver heads were performed to determine the anatomy of the terminal nerves in the upper eyelid. Vertically oriented nerves, which are commonly identified in a preseptal location in the upper eyelid, were determined to be sensory nerves, most commonly originating from the supraorbital nerve (V1). Facial nerve (VII) dissections were also performed, with specific attention paid to the temporal branch. The facial nerve innervates the orbicularis muscle on its deep surface, both at the most temporal aspect of the muscle as well as along the supraorbital rim. No motor fibers could be traced into the upper eyelid and no anastomosis was noted between the temporal branch of the facial nerve (VII) and the supraorbital nerve (V1). PMID- 8193066 TI - Schizophrenia, training paradigms, and the Wisconsin Card Sorting Test redux. AB - The question of whether and to what extent poor performance on the Wisconsin Card Sorting Test (WCST) in patients with schizophrenia can be improved with coaching has been controversial. We review relevant studies with particular reference to the following issues: (1) can improvement occur? (2) if improvement does occur, what is its significance? and (3) what is the association between performance and neurophysiology? The studies indicate that in patients with schizophrenia performance can frequently be improved, but usually remains in the abnormal range. Similar results for memory measures have been reported in patients with amnesias or dementias of known neurological origin. This suggests that simple dichotomies between neurologic and psychological explanations of cognitive impairment and potential amelioration of such impairment may be inadequate. Comparisons of the results of studies using the WCST as a clinical tool with binary cut-off scores to define normal and abnormal, as a measure of neuropsychological function along a continuum, and as an activation stimulus to probe neurophysiology suggest that absolute WCST scores may not always accurately gauge the functional integrity of neural systems dedicated to the task. This situation may arise because of individual differences in endowment and in the capacity for neuronal compensation, as well as measurement error. Given these issues, caution is advised in the interpretation of WCST scores, which are best understood as representing a final common cognitive pathway that can be the product of diverse psychological, physiological, and neuroanatomic mechanisms. PMID- 8193068 TI - Orbital volume augmentation with subperiosteal room-temperature-vulcanized silicone implants: a clinical and histopathologic study. AB - Enophthalmos, a clinical feature of the anophthalmic orbit, often produces a considerable cosmetic deformity. Management of this condition includes surgical volume augmentation with orbital implants. Several types of materials with different shapes have been used with variable success rates. Between 1984 and 1990, we treated 84 anophthalmic patients with room temperature vulcanized (RTV) subperiosteal silicone implants. Adequate volume augmentation and correction of the apparent enophthalmos was achieved in 75 patients. Extended patient follow up, analysis of data and results, histopathologic assessment of implant capsules, and management of complications have provided a unique opportunity to study the efficacy of the surgery. We present our experience in the management of this condition. PMID- 8193069 TI - Retroscleral-intraconal RTV silicone implants: an alternative technique for volume replacement post-extruding eviscerated spherical implants. AB - Two patients with extruded implants postevisceration were assessed and managed with room temperature vulcanized (RTV) silicone implants placed in the retroscleral-intraconal space. The technique described is an alternative and simple surgical method that provides utilization of the remaining sclera, anterior support for the implant, and adequate volume replacement. The postoperative follow-up is relatively short, and clinical and radiologic (CT scan) investigations support the efficacy of the procedure. To the best of our knowledge, such a surgical alternative has not been reported. PMID- 8193070 TI - Congenital synkinetic movements associated with elevation of the upper eyelid. AB - Congenital synkinetic movement of the upper eyelid is rare. In this case report, we present a 4-year-old patient with a left upper eyelid ptosis that improved on abduction and became worse on adduction. The patient also had congenital esotropia and superior rectus palsy. Strabismus surgery was performed, and excellent surgical results were achieved. A 17-mm left levator aponeurectomy and myectomy was later performed with satisfactory results. Pathology studies of the levator muscle and aponeurosis showed no evidence of inflammation, degeneration, or atrophy. Electron microscopy showed no skeletal muscle abnormality. We postulate that this congenital synkinetic movement reflects an incomplete nerve cell dying process that occurs during the embryonic phase of development. PMID- 8193071 TI - Extraocular muscle enlargement after orbital decompression for Graves' ophthalmopathy. AB - Three patients who had orbital decompression for compressive optic neuropathy secondary to Graves' ophthalmopathy are presented. Despite initial improvement in their visual acuity, all of the patients experienced subsequent relapse due to progressive enlargement of the extraocular muscles, resulting in recurrent compressive optic neuropathy. Management consisted of reoperation, systemic prednisone, and retrobulbar radiation. Enlargement of the extraocular muscles is felt to be caused by continuation of the autoimmune process and/or expansion of the extraocular muscles after slitting of the periorbita and bony removal of the orbital walls. PMID- 8193072 TI - Benign approach to a malignant orbital tumor: metastatic renal cell carcinoma. AB - A well-circumscribed, pseudoencapsulated benign-appearing lesion in the retrobulbar orbit of a 50-year-old man was found to be a metastatic renal cell carcinoma. The patient had a nephrectomy for renal cell carcinoma 15 years before, and had developed four other isolated metastases over the preceding 8 years. He had a further distant metastasis 1 year later, but is living and well 4 years after excision of the orbital tumor. Metastatic renal cell carcinoma of the orbit may have very benign characteristics, both clinically and radiographically, and can often be managed effectively by local excision with prolonged survival. PMID- 8193073 TI - Adenoid cystic carcinoma of the lacrimal gland: a case report. AB - A 70-year-old woman was referred to our clinic for evaluation and treatment of a recurring case of adenoid cystic carcinoma of the lacrimal gland. She had been diagnosed with this tumor three years earlier, and a local resection was attempted on two occasions. We encountered this patient on the third recurrence of the tumor, and a thorough work-up revealed extensive local involvement but no metastases. A total exenteration of the right orbit was then performed with aggressive resection of local extension followed by irradiation. Thirteen years later, our patient presented with metastases throughout her scalp. She died shortly thereafter, having survived a total of 16.5 years after the time of her initial treatment and 13 years after exenteration with bony removal of the orbit and irradiation. A review of the literature reveals that this patient had one of the longest reported survival times in the literature from the time of initial treatment. Also noteworthy is the 13 years this patient survived after aggressive surgical resection combined with radiotherapy following two previous incomplete resections. PMID- 8193074 TI - Ophthalmic manifestations of acanthosis nigricans. AB - A 77-year-old man had fleshy papillomatous lesions on his eyelid margins, which initially were accompanied by lesions on his lips and tongue and plaques on his scrotum, areolae, neck, axillae, and hands. He had had adenocarcinoma of the sigmoid colon and stomach. Based on the clinical findings and histopathologic evaluation of the eyelids (showing papillomatous changes with hyperkeratosis and mild acanthosis), the diagnosis of acanthosis nigricans was made. Acanthosis nigricans may be benign or malignant; in this patient it was malignant. The malignant form is usually of gastrointestinal origin, and in adults may be a marker for an occult malignancy. PMID- 8193075 TI - Granuloma after augmentation of the eyelids with liquid silicone: an electron microscopic study. AB - Granuloma after liquid silicone augmentation of the upper eyelids was studied by light and electron microscopy and energy dispersive x-ray analysis. Light microscopy showed proliferation of collagen fibers and many phagocytic macrophages with vacuoles. Electron microscopy showed many vacuoles in phagocytic macrophages, fragmentary myofibrils, and proliferation of collagen fibers. Vacuoles in phagocytic macrophages contained silicone that was demonstrated by energy dispersive x-ray analysis. The present case suggests that liquid silicone injection in the eyelid can induce degeneration of the orbicularis oculi muscle in addition to granuloma formation. PMID- 8193076 TI - Medical and surgical management of chemosis after blepharoplasty. AB - Chemosis--conjunctival edema--occurs frequently after direct surgical or accidental trauma. In most cases, it resolves spontaneously. We report three patients with a spectrum of persistent chemosis after lower blepharoplasty. Etiologic factors are presented, and the management is reviewed. PMID- 8193077 TI - A procedure for the reconstruction of the lateral palpebral canthus. AB - Tessier's classification of facial clefts has been quite adequate. This cleft occurs as an isolated anomaly or as a coloboma associated with Treacher Collins syndrome, Goldenhar's syndrome, or hemifacial microsomia. We present a procedure developed to reconstruct the lateral canthus. PMID- 8193078 TI - Tarsal plate banking. PMID- 8193079 TI - The effect of anti-CD4 monoclonal antibody treatment on immunopathological changes in psoriatic skin. AB - Recent clinical studies which showed the therapeutic effect of cyclosporin A and of anti-CD4 MoAb emphasized the role of activated CD4+ T cells infiltrating the lesional skin in the pathogenesis of psoriasis. The aim of the present study was to analyze the mode of action of anti-CD4 MoAb in 3 psoriatic patients who experienced an anti-CD4 MoAb-induced clinical improvement maximal 3-4 weeks after the onset of an 8-day therapy. We evaluated the effect of anti-CD4 MoAb treatment on the phenotype of resident and passenger inflammatory skin cells in lesional skin samples. We observed a gradual improvement of 3 out of 4 histopathologic features including parakeratosis, papillomatosis and acanthosis. In the dermis there was no modification in the density of the dermal mononuclear cell infiltrate, which consisted mainly of CD3+, CD45RO+, TCR alpha beta+, CD11a+, HLA DR+T cells with a CD4/CD8 cell ratio of 1.5/1. Therefore as previously observed for peripheral blood mononuclear cells, the number of CD4+ T cells infiltrating the dermis remained unaffected by the treatment. In contrast, CD4 MoAb treatment was associated with drastic changes in the epidermis. These included a decrease in both CD4+ and CD8+ epidermal T cell infiltrate, diminished numbers of ICAM-1+ and HLA-DR+ keratinocytes and restored numbers of CD1a+ epidermal Langerhans cells. We conclude from this study that clinical improvement of psoriasis by anti CD4 MoAb therapy paralleled: (1) a decrease in epidermal T cells, and (2) a down regulation of keratinocyte activation markers (ICAM-1 and HLA-DR). These results suggest that the observed changes are secondary to down-regulation of inflammatory cytokine production by T cells in situ. PMID- 8193080 TI - Increased SS bonds in chronic solar elastosis: a study with N-(7-dimethylamino-4 methyl-3-coumarinyl) maleimide (DACM) stain. AB - We have studied the distribution of SH groups and SS linkages in solar elastosis, in comparison with that in aged and juvenile sun-unexposed skin, using N-(7 dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM) stain. In heavy solar elastosis we found increased fluorescence for SS bonds in the upper and middle reticular dermis in the elastotic masses; these were separated from the epidermis by a network of actinically-damaged, SS-positive elastic fibers, showing irregularly and variously interwoven oxytalan and elaunic fibers. These latter, unlike the elastotic masses, revealed also SH groups. In moderate and weak elastosis, where the thick irregular masses were absent, the fluorescence for SH and SS linkages was present in equal proportions in the altered elastic fibers; collagen bundles revealed only fluorescence for SS bonds. Aged and juvenile sun unexposed skin showed the same proportions of SH and SS linkages in the changed elastic fibers. Collagen bundles of aged and juvenile skin showed fluorescence for SS bonds; SH groups were present on a few collagen fibers only in aged skin. Our results are consistent with opinion supporting an elastic origin of elastotic degeneration, which could be the consequence of a defect, due to chronic solar exposure, in one of the steps--degradation or synthesis--of metabolic turnover of elastic fibers, resulting in abnormal and excessive polypeptide chains extremely rich in disulfide bonds. PMID- 8193081 TI - Regulatory effects of 1,25-dihydroxyvitamin D3 and a novel vitamin D3 analogue MC903 on secretion of interleukin-1 alpha (IL-1 alpha) and IL-8 by normal human keratinocytes and a human squamous cell carcinoma cell line (HSC-1). AB - Pro-inflammatory cytokines mediate their biological functions after they are secreted or released from intracellular to extracellular milieu. Keratinocytes have proven to be able to produce various cytokines including IL-1 and IL-8. Dysregulations of IL-1 and IL-8 were found in psoriatic lesions. Recently, vitamin D3 (VD3) was found to be an effective and safe therapy for psoriasis. In the present study, we investigated the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its analogue MC903 on IL-1 alpha and IL-8 secretion by human keratinocytes in vitro. Cultured normal human keratinocytes (NHKs) produced considerable amounts of IL-1 alpha but secreted less. In contrast, they produced less IL-8 and almost all molecules were secreted to the culture supernatants. Treatment of unstimulated NHKs with 1,25(OH)2D3 or MC903 showed little effects on IL-1 alpha production and secretion though they slightly enhanced IL-8. When NHKs were stimulated with tumour necrosis factor-alpha (TNF alpha), both IL-1 alpha and IL-8 secretions were enhanced and these enhancements were inhibited by 1,25(OH)2D3 or MC903. Stimulation of NHKs with phorbol 12-myristate 13 acetate(PMA) and lipopolysaccharide(LPS) resulted in an increase of IL-8 and decrease of IL-1 alpha in the culture supernatants. Addition of 1,25(OH)2D3 or MC903 inhibited the increased secretion of IL-8 but restored decreased secretion of IL-1 alpha from stimulated NHKs dose dependently. Hydrocortisone and cyclosporin A showed similar inhibitory effects on PMA/LPS-increased IL-8 secretion from NHKs but had little effect of restoring IL-1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193082 TI - Ultraviolet-B irradiation deforms the configuration of elastic fibers during the induction of actinic elastosis in rats. AB - We used scanning electron microscopy combined with perfusion fixation, resin injection and a selective digestion procedure to determine the effects of ultraviolet-B (UVB) radiation on the three-dimensional architecture of elastic fibers of rat skin. Chronic irradiation with a suberythematous dose of UVB (3 times/week for 12 weeks) produced a tortuous deformation of the superficial elastic fibers in the skin of the rat sole which normally are linearly arranged. Using computer analysis, we evaluated 40 individuals elastic fibers every 3 weeks for 12 weeks following the irradiation. This procedure confirmed the increasing tortuosity of the fibers, which was related to a decline in the elastic property of the skin in situ. Fine elastic branches developed among the deformed fibers and eventually anastomosed to produce an irregular network in the superficial dermal connective tissue, which may correspond to the development of actinic elastosis, that is, the UV-related accumulation of elastic fiber material. PMID- 8193083 TI - Evaluation of ultraviolet-A protection by sunscreen agents using a mouse model of contact photoallergy. AB - This study was conducted to investigate in vivo evaluation of protectiveness by sunscreens in the UVA range using a mouse model of contact photoallergy (CPS) to 3,3',4',5-tetrachlorosalicylanilide (TCSA). Mice were sensitized with TCSA painting plus UVA irradiation (TCSA/UVA) on the abdomen and, 5 days later, challenged with TCSA/UVA on the earlobe. Each of four sunscreen agents, benzophenone-3, Parsol 1789, p-aminobenzoic acid, and 2-ethyl-hexyl-p methoxycinnamate, was applied to the earlobes before irradiation. Their protective efficacy was evaluated in the degree of inhibition of both ear swelling responses and TCSA-epidermal cell photoadduct formation. Two UVA absorbing sunscreens, benzophenone-3 and Parsol 1789, dramatically inhibited the ear swelling response, while the two UVB-absorbers exhibited a much less suppressive effect. The UVA-absorbing agents functioned via inhibiting the formation of TCSA-epidermal cell photoadducts. This method is thought to be useful for in vivo estimation of UVA protection provided by sunscreens against the exquisite sensitivity involved in photoallergy. PMID- 8193084 TI - Expression of c-fos proto-oncogene mRNA in non-melanoma skin cancer. AB - c-fos is a member of the proto-oncogene family and is implicated in the modulation of cell proliferation and differentiation. Previous studies have shown that the c-fos gene expression is regulated in a tissue specific manner. In order to clarify the role of the c-fos gene in human epidermis, we have investigated c fos mRNA expression in both normal skin and non-melanoma skin cancer. In normal skin the intensity of the c-fos mRNA expression in spinous cells was found to be stronger than that observed in basal cells. In lesions of solar keratosis and Bowen's disease the spinous cells also showed stronger c-fos mRNA expression than in basal cells. In two of four cases of Bowen's disease some upper spinous cells showed very strong mRNA expression of the c-fos gene. In squamous cell carcinomas studied there was considerable variation in the intensity of c-fos mRNA expression. Our findings indicate that the degree of c-fos mRNA expression is related to the degree of dysplasia present. In all cases of basal cell carcinoma examined the c-fos mRNA expression was markedly decreased. These results suggest that c-fos expression may be involved in the differentiation of human keratinocytes in vivo rather than in the neoplastic process itself. PMID- 8193085 TI - Investigations on plasma levels of mast cell mediators in acute atopic dermatitis. AB - Skin mast cells have been proposed to be involved in the pathogenesis of acute and chronic phases of atopic dermatitis (AD). The aim of the present study was to investigate the significance of different mast cell mediators during acute exacerbation of this frequent skin disease. Plasma levels from 19 patients with AD were screened for elevation of the mast cell-specific protease tryptase, the biogene amine histamine, and the arachidonic acid metabolite prostaglandin D2. None of the patients showed elevated plasma levels of these three mediators, whereas the mean serum IgE level was strongly elevated. We conclude that the investigated mediators are either only active on the cutaneous level or that other mediators are responsible for the development of the acute eczematous and pruritic skin reactions. Alternatively, the assays could have been insufficiently sensitive since some studies have demonstrated increased plasma histamine levels, e.g. after food challenge of such patients. PMID- 8193086 TI - Capillary changes in angiokeratoma corporis diffusum Fabry. AB - We report on capillary changes on the Sulcus matricis unguis in a patient with an established angiokeratoma corporis diffusum Fabry. A fasciculated ramification of the capillary in 2-5 loops, which is not found in healthy individuals and that until now has solely been described in patients with vasculitis, was detected. The question now arises whether these are initial changes in the disease which later lead to manifested angiokeratomas. Further investigations will show if, and to what extent, these observations can contribute to further clarification of the developmental method of acroparaethesiae, which are part of the principal signs of Morbus Fabry. PMID- 8193087 TI - Dexamethasone pulse treatment in disseminated porokeratosis of Mibelli. PMID- 8193088 TI - Medical negligence disputes: alternatives to litigation. PMID- 8193089 TI - HIV infection and the gynaecologist. PMID- 8193090 TI - Where are we with Doppler? PMID- 8193091 TI - Working towards a European strategy for intervention to reduce vertical transmission of HIV. PMID- 8193092 TI - Investigation of folate intake and metabolism in women who have had two pregnancies complicated by neural tube defects. AB - OBJECT: To investigate folate intake and blood levels of folic acid and vitamin C in women with and without a history of two NTD-affected pregnancies and to measure the increase in serum folate following ingestion of orange juice. SUBJECTS: Sixteen women with a history of two NTD-affected infants and 16 controls with no such history, none of whom were either pregnant or taking vitamin supplements. The orange juice loading test was carried out on eight matched pairs. MAIN OUTCOME MEASURES: Dietary intake of folate was assessed by questionnaire and blood levels of folate and vitamin C were measured. RESULTS: There was no evidence of decreased intake of folate in subjects who had had two NTD-affected pregnancies. In controls, both serum and red cell folate showed significant correlation with dietary folate, while in subjects there was no such correlation. Subjects also had smaller increases in serum folate following an oral load than controls, although the differences were not significant. CONCLUSION: Women who have had two NTD-affected pregnancies may have defective folate metabolism. Further investigations on short term utilisation of ingested food folates in these women are required. PMID- 8193093 TI - Neonatal platelet reactivity and serum thromboxane B2 production in whole blood: the effect of maternal low dose aspirin. AB - OBJECTIVES: Concern has been expressed about possible neonatal side effects after the use of maternal anti-platelet agents in pregnancy, particularly low dose aspirin treatment. We have studied neonatal platelet behaviour using whole blood techniques, and assessed the neonatal effect of the maternal ingestion of 60 mg aspirin daily. DESIGN: Cross sectional and randomised, double-blind, placebo controlled. SETTING: University hospital. SUBJECTS: 1. Eight normal women, studied before conception, and their infants. 2. Twenty-four infants whose mothers had been randomised to receive either 60 mg aspirin daily, or placebo, in double-blind fashion. METHODS: The Clay Adams Ultra Flo 100 whole blood single platelet counter was employed to measure platelet aggregation in response to various agonists. The platelet release reaction was also measured in whole blood, and serum thromboxane B2 (TxB2) production was measured by radio-immunoassay. Umbilical cord blood samples were obtained at delivery. RESULTS: 1. Neonatal platelet aggregation induced by adrenaline, ADP and platelet activating factor was reduced in comparison with their mothers (P < 0.01), whereas the neonatal platelet release reaction was reduced when stimulated by collagen and U46619 (a thromboxane mimetic) (P < 0.01). Serum TxB2 production was similar in mothers and babies. 2. Neonatal platelet aggregation, release reaction and serum TxB2 production were not significantly reduced in infants exposed to maternal aspirin in comparison with those neonates exposed to maternal placebo. This is in contrast to the effect on maternal platelets. CONCLUSIONS: Although only a small number of patients were studied, we interpret this as a relative sparing of neonatal platelet reactivity due to the presystemic action of low dose aspirin. PMID- 8193094 TI - Platelet activation in normotensive and hypertensive pregnancies complicated by intrauterine growth retardation. AB - OBJECTIVE: To study platelet function in normotensive and hypertensive intrauterine growth retardation (IUGR). DESIGN: ADP and collagen induced whole blood platelet aggregation, beta-thromboglobulin release and platelet count were measured in the IUGR groups at a mean gestational age of 36 weeks (28-40), and at 1, 24, 48 h and six weeks post delivery. The normal pregnancy group were studied serially at 12, 20, 28, 32 and 36 weeks of gestation and at 1, 24, 48 h and six weeks post delivery. SETTING: Trinity College Medical School, St. James's Hospital, Dublin. SUBJECTS: Twenty-nine women with a fetus with diagnosed IUGR were recruited for the study. Of these, 15 were normotensive throughout their pregnancy and the remaining 14 pregnancies were complicated by both hypertension and proteinuria. Twenty healthy primigravida acted as controls. RESULTS: In the hypertensive IUGR group, levels of collagen and ADP induced aggregation were almost 50% lower before delivery than in normal pregnancy. Platelet count in the hypertensive group was decreased by 30% compared with normal pregnancy. Levels of beta-thromboglobulin were 40 to 50% higher in both the normotensive and hypertensive IUGR groups compared with normal pregnancy. Unlike the hypertensive IUGR group, the normotensive IUGR group showed similar levels of platelet count and ADP and collagen induced aggregation to those found at 36 weeks of normal pregnancy. In the early puerperium of hypertensive pregnancies, the platelet parameters measured returned gradually to normal. The normotensive IUGR group had increased levels of ADP induced aggregation in the first 24 to 48 h post delivery. The platelet count in the normotensive but not the hypertensive group correlated with birthweight. CONCLUSIONS: Normotensive and hypertensive IUGR are accompanied by platelet activation. In normotensive IUGR, this activation appears to be confined to the uteroplacental circulation. In hypertensive IUGR, the results suggest that platelet activation also extends into the peripheral circulation resulting in a reduced platelet responsiveness and a lower platelet count. Release of vasoactive amines from activated platelets in the peripheral circulation may be responsible for the clinical syndrome of hypertension and proteinuria present in pregnancies complicated by pre-eclampsia and IUGR but absent in normotensive IUGR. PMID- 8193095 TI - Serum ferritin and cobalamin in growth retarded fetuses. AB - OBJECTIVE: To examine fetal and maternal serum cobalamin and ferritin concentrations in pregnancies complicated by fetal growth retardation. SETTING: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital Medical School, London. DESIGN: Cross sectional study. SUBJECTS: Fetal blood samples obtained by cordocentesis from 20 growth retarded fetuses at 26 to 36 weeks of gestation. Maternal venous blood was also collected and serum ferritin and cobalamin concentrations were measured by radio-immunoassay in the fetal and maternal samples. RESULTS: In the growth retarded group, the mean fetal serum concentration of cobalamin was higher than the normal mean for gestation (t = 3.27, P < 0.01), and this increase was significantly associated with fetal acidaemia (r = -0.686, P < 0.001) and erythroblastosis (r = 0.731, P < 0.001). In contrast, the fetal to maternal ferritin ratio was significantly reduced; there was a nonsignificant decrease in fetal serum and an increase in maternal serum ferritin concentration. There was an association between fetal serum ferritin concentration and erythrocyte count (r = -0.612, P < 0.01). CONCLUSIONS: In placental insufficiency, as in postnatal starvation and Kwashiorkor syndrome, uptake and storage of cobalamin by the fetal liver may be impaired. The decrease in fetal to maternal ratio of ferritin could be the consequence of impaired placental perfusion. PMID- 8193096 TI - Ductus venosus flow velocity waveforms in relation to fetal behavioural states. AB - OBJECTIVES: To establish the reproducibility of flow velocity waveforms in the human ductus venosus and to assess the influence of fetal behavioural states on these waveforms in normal term fetuses. DESIGN: Reproducibility of Doppler waveform recording and analysis was studied in 10 normal pregnancies. The relation between ductus venosus flow velocities and behavioural states was investigated in 19 other term fetuses. Time-averaged, peak systolic, peak diastolic velocity, peak systolic/diastolic ratio and period time were calculated in both cross sectional studies. SETTING: Outpatient clinic, department of obstetrics (prenatal diagnosis section), Academic Hospital, Rotterdam--Dijkzigt. SUBJECTS: Twenty-nine women with normal singleton pregnancies at 36 to 39 weeks of gestation, resulting in uncomplicated births of healthy infants. RESULTS: Within-patient coefficients of variation, ductus venosus waveform recordings were approximately 8 to 10% except for the peak systolic/diastolic ratio (4.3%). A decrease of approximately 30% was established for peak systolic, peak diastolic velocity and time-averaged velocity during behavioural state 1F (quiet sleep) as compared with state 2F (active sleep). CONCLUSIONS: Flow velocity waveform recording in the ductus venosus demonstrates acceptable reproducibility. Fetal behavioural state-dependent changes were observed, suggesting a redistribution of umbilical venous blood through the ductus venosus shunt during the quiet sleep state. PMID- 8193097 TI - Initial experience with supracervical laparoscopic hysterectomy and removal of the cervical transformation zone. AB - OBJECTIVE: To assess the feasibility and outcome of laparoscopic supracervical hysterectomy with removal of the cervical transformation zone. DESIGN: A prospective clinical study. SETTING: The department of Gynaecology, Royal Surrey County Hospital, Guildford. SUBJECTS: Eleven consecutive women who were on the waiting list for abdominal hysterectomy and fulfilled the selection criteria. INTERVENTION: Laparoscopic supracervical hysterectomy using a modification of the classical abdominal supracervical hysterectomy technique with removal of the cervical transformation zone. MAIN OUTCOME MEASURES: Operating time, blood loss, duration of hospital stay, time to full recovery and complications. RESULTS: All 11 procedures were successfully completed laparoscopically. The mean operating time was 111 min, and mean blood loss was 185 ml. The mean duration of hospital stay was three days, and the mean time to full recovery was 20 days. There were no major complications. CONCLUSIONS: Laparoscopic supracervical hysterectomy appears to result in a shorter hospital stay and more rapid recovery than total abdominal hysterectomy. This shortened convalescence is of benefit to the patient. The operation appears to be safe when carried out by surgeons experienced in laparoscopic surgery. A randomised comparative study with total abdominal hysterectomy is currently being undertaken. PMID- 8193098 TI - Age related changes in the female reproductive cycle. AB - OBJECTIVE: To investigate the effect of age on the control of the reproductive cycle in regularly menstruating women. DESIGN: In this prospective study all women were seen regularly during both the follicular and luteal phases. Ultrasound scanning was used to confirm ovulation and measurements were taken to assess follicular development and endometrial thickness. Serum gonadotrophin levels on day 4 of the cycle, the maximum periovulatory oestradiol and progesterone on the seventh day after ovulation were measured and compared in different age groups. SUBJECTS & SETTING: Fifty-six healthy, regularly menstruating women were recruited from volunteers amongst staff of the University Hospital of South Manchester. RESULTS: Ovulation occurred later in the cycle for older women, with mean follicular phase length increasing from 13.9 days (in group 21-25 years) to 15.9 days (in group 37-45 years (P < 0.05). The mean of the maximum follicular diameter prior to rupture was significantly smaller in the older women: 16.7 mm in the 37 to 45 years old group compared with 19.6 mm, 21.6 mm and 21.3 mm in the 21 to 25, 26 to 31 and 32 to 36 years old age groups, respectively (P < 0.001). The maximum thickness of the endometrium in the luteal phase was greatest for older women: 15.9 mm in the age group 37 to 45 years compared with 12.1 mm in the age group 21 to 25 years (P < 0.001). Serum gonadotrophin concentrations during menses were higher with increased age; mean follicle stimulating hormone was 4.8 iu/l in the age group 21 to 25 years, and 8.5 iu/l in the age group 37 to 45 years (P < 0.001). Mean luteinising hormone was 4.5 iu/l in age group 21 to 25 years and 7.21 iu/l in age group 37 to 45 years (P < 0.001). Mean ovarian steroid concentrations were no different. CONCLUSIONS: These data illustrate significant age related differences in the pituitary-ovarian axis and endometrial thickness. This has implications for the management of older women in assisted reproduction and fertility control programmes. PMID- 8193099 TI - Digital imaging colposcopy, image analysis and quantification of the colposcopic image. AB - OBJECTIVE: To investigate the use of a digital imaging system for colposcopy, its use for image analysis and quantification of the colposcopic features that may predict histological outcome as defined by large loop excision of transformation zone. DESIGN: Prospective programme study of all patients undergoing colposcopy for cytological abnormalities. SETTING: Dudley Road Hospital, Birmingham. SUBJECTS: Fifty consecutive patients having cytological and colposcopic abnormality treated with large loop excision of transformation zone formed the study group. MAIN OUTCOME MEASURES: Pretreatment and colposcopic features correlated with histological diagnosis of excised transformation zone. RESULTS: Index cytology and current smoking status are the most important variables for prediction of histological diagnosis. Other important variables are focality of lesion, surface pattern, intercapillary distance and degree of acetowhiteness. CONCLUSION: Digital imaging colposcopy allows image capture, processing and objective analysis. This methodology holds advantages for basic and clinical research, teaching, diagnostics and clinical audit. The system can act as a quality control tool for colposcopy units. This system should prove invaluable for further quantitative studies, for natural history studies and for those patients with deferred treatment of their cytological and colposcopic abnormalities. The statistical models described may be incorporated into the system and can aid the colposcopist in management of the woman with abnormal cervical cytology and colposcopic abnormality. PMID- 8193100 TI - Lack of association between maternal phosphoglucomutase-1 phenotype and fetal macrosomia in diabetic pregnancy. AB - OBJECTIVE: To assess the reports that maternal phosphoglucomutase-1 (PGM1) phenotype is highly related to macrosomia in diabetic pregnancy. This could be either a direct metabolic phenomenon, or the PGM1 locus could be a marker for a tightly linked gene involved in the maternal control of fetal growth. DESIGN: A comparative biochemical genetic study. SETTING: A large diabetic pregnancy clinic. SUBJECTS: One hundred and fifty-two women who had diabetes during pregnancy, 136 being insulin dependent before pregnancy. Two hundred and thirty six women without pre-existing medical or pregnancy complications who functioned as a control group. MEASURES: PGM1 phenotype was assessed by conventional electrophoresis and subgroups were examined using iso-electric focusing. OUTCOME: Standardised birthweight was corrected for sex, maternal parity and gestation confirmed in every case by early pregnancy ultrasound. Maternal diabetes control was assessed by glycosylated haemoglobin. RESULTS: No differences were found in the observed phenotype frequencies for diabetics and control pregnant women. No association between PGM1 phenotype and macrosomia in diabetic pregnancy was found. PGM1 did not make a significant contribution to birthweight, standardised birthweight, length or ponderal index of the baby as assessed by multiple regression. CONCLUSIONS: Our study of a larger number of insulin dependent diabetics in Scotland makes the claim that macrosomia in diabetic pregnancy is associated with PGM1 phenotype unlikely to be of general significance. PMID- 8193101 TI - Prenatal determination of human platelet antigen type using DNA amplification following amniocentesis. AB - OBJECTIVES: To demonstrate that fetal human platelet antigen (HPA1) type can be determined, without the need for fetal blood sampling, by amplification of fetal DNA from amniotic fluid cells using polymerase chain reaction and allele specific oligonucleotide hybridisation. DESIGN: Oligonucleotide DNA primers were designed to amplify a portion of the platelet glycoprotein GpIIIa gene which spans the site of the single base change which differentiates HPA1a from HPA1b. Specific oligonucleotides were designed to hybridise either to the amplified HPA1a allele or to the HPA1b allele. Amniotic cells were used as the DNA template both directly and following formal isolation of DNA. Fetal HPA1 type, determined by this method in fifteen pregnancies not at risk of perinatal alloimmune thrombocytopaenia, was compared to typing of fetal blood obtained following cordocentesis. The methodology was then used to HPA type the fetus in two pregnancies at risk of the disease. SETTING: Department of Molecular Biology and Centre for Fetal Care, Queen Charlotte's Hospital. SUBJECTS: Fifteen women undergoing amniocentesis and fetal blood sampling for other indications and two women at risk of perinatal allo-immune thrombocytopaenia whose partners were heterozygotes. RESULTS: In the 15 control cases and the two clinical cases, determination of fetal HPA1 type from amniotic fluid cells agreed with typing of fetal blood. There was no difference in the efficiency of amplification from amniotic fluid cells directly or from isolated DNA. CONCLUSIONS: Fetal HPA type may be reliably determined by amplification of DNA from amniotic fluid cells, eliminating the need for fetal blood sampling or immunoglobulin administration when the fetus is HPA1a negative. PMID- 8193102 TI - How well is fetal blood sampling used in clinical practice? PMID- 8193103 TI - Length of hospital stay after vaginal hysterectomy. PMID- 8193104 TI - The use of magnetic resonance imaging in the assessment of the cervical hydration state. PMID- 8193105 TI - Successful use of a Sengstaken-Blakemore tube to control massive postpartum haemorrhage. PMID- 8193106 TI - Multiple gestation following gonadotrophin releasing hormone therapy for the treatment of minimal endometriosis. PMID- 8193107 TI - The combination of magnesium sulphate and nifedipine: a cause of neuromuscular blockade. PMID- 8193108 TI - Cardiogenic pulmonary oedema: presentation of pre-eclampsia exacerbated by prostaglandin abortifacients. PMID- 8193109 TI - Wound recurrence by implantation of a borderline ovarian tumour following laparoscopic removal. PMID- 8193110 TI - Polycystic ovaries and levels of gonadotrophins and androgens in recurrent miscarriage: prospective study in 50 women. PMID- 8193111 TI - Undiagnosed breech. PMID- 8193112 TI - Hyperammonaemia after transcervical resection of the endometrium. PMID- 8193113 TI - The outcome of pregnancy after CO2 laser conisation of the cervix. PMID- 8193114 TI - The use of gemeprost pessaries to arrest postpartum haemorrhage. PMID- 8193115 TI - The use of gemeprost pessaries to arrest postpartum haemorrhage. PMID- 8193116 TI - Structural determinants of enzymatic processivity. AB - A processive enzyme binds a polymeric substrate and catalyzes a series of similar chemical reactions along that polymer before releasing the fully modified polymer to solvent. Bovine pancreatic ribonuclease A (RNase A) is a nonprocessive endoribonuclease that binds the bases of adjacent RNA residues in three enzymic subsites: B1, B2, and B3. The B1 subsite binds only to residues having a pyrimidine base, while the B2 subsite prefers adenine and the B3 subsite prefers a purine base. RNase A mutants were created in which all natural amino acids were substituted for Thr45 or Phe120, two residues of the B1 subsite. These pools of mutant enzymes were screened for mutants that catalyze the cleavage of RNA after purine residues. The Ala45 and Gly45 enzymes cleave poly(A), poly(C), and poly(U) efficiently and with 10(3)-10(5)-fold increases in purine/pyrimidine specificity. Thus, substrate binding can be uncoupled from substrate turnover in catalysis by RNase A. In addition, both mutant enzymes cleave poly(A) processively. Our results provide a new paradigm: a processive enzyme has subsites, each specific for a repeating motif within a polymeric substrate. Further, we propose that processive enzymes bind more tightly to motifs that do repeat than to those that do not. PMID- 8193117 TI - Inhibition of ATP binding to myofibrils and acto-myosin subfragment 1 by caged ATP. AB - The inhibitory effect of P3-[1-(2-nitrophenyl)ethyl]adenosine 5'-triphosphate (caged ATP) on the binding of Mg2+-ATP to myofibrils was investigated. The most sensitive method was found to be the monitoring of single turnovers of [gamma 32P] ATP hydrolysis using the quench flow technique. The method was tested using ADP, which was found to have an inhibition constant of 145 microM, in agreement with previous reports. Caged ATP behaved as a simple competitive inhibitor of ATP binding with an inhibition constant of 1.6 mM. The inhibitory effect of these ligands on the binding of ATP to acto-myosin subfragment 1 was investigated using the same method. The inhibition constants of caged ATP and ADP were found to be 0.35 mM and 50 microM, respectively. This inhibitory effect of caged ATP on ATP binding accounts for the lower rate of ATP binding to fibers, deduced from caged ATP [(0.5-1) x 10(6) M-1 s-1], than that reported for acto-S1 (3.5 x 10(6) M-1 s 1) [Goldman, Y. E., Hibberd, M. G., & Trentham, D. R. (1984) J. Physiol. (London) 354, 577]. PMID- 8193118 TI - 1H and 15N NMR assignments of PsaE, a photosystem I subunit from the cyanobacterium Synechococcus sp. strain PCC 7002. AB - PsaE is a highly conserved, water-soluble protein of the photosystem I reaction center complexes of cyanobacteria, algae, and green plants. Along with the PsaC and PsaD proteins, the PsaE protein binds to the stromal surface of photosystem I and is required for cyclic electron transport in Synechococcus sp. strain PCC 7002 [Yu, L., Zhao, J., Muhlenhoff, U., Bryant, D.A., & Golbeck, J.H. (1993) Plant Physiol. 103, 171-180]. The psaE gene from this cyanobacterium encodes a mature protein of 69 amino acid residues and has recently been overexpressed in Escherichia coli [Zhao, J., Snyder, W.B., Muhlenhoff, U., Rhiel, E., Warren, P. V., Golbeck, J. H., & Bryant, D. A. (1993) Mol. Microbiol. 9, 183-194]. By using both unlabeled and uniformly 15N-labeled protein in a series of two- and three dimensional NMR experiments, complete 1H and 15N amide resonance assignments were made. The major secondary structural element of PsaE is a five-stranded antiparallel beta-sheet. The five strands extend as follows: beta A, residues 7 10; beta B, residues 21-26; beta C, residues 36-39; beta D, residues 57-60; and beta E, residues 65-68. The topology is represented by (+1, +1, +1, -4x); it brings the first and last strands, and consequently the N- and C-termini, together. The protein has an extensive hydrophobic core organized around a conserved phenylalanine residue (Phe-40); another of its distinctive features is a segment extending from residue 42 to residue 56 devoid of dipolar contacts with the beta-sheet. The pK1/2 of the sole histidine residue (His-63) was determined to be 5.4. PMID- 8193119 TI - Three-dimensional solution structure of PsaE from the cyanobacterium Synechococcus sp. strain PCC 7002, a photosystem I protein that shows structural homology with SH3 domains. AB - PsaE is a 69 amino acid polypeptide from photosystem I present on the stromal side of the thylakoid membrane. The three-dimensional solution structure of this protein from the cyanobacterium Synechococcus sp. strain PCC 7002 was determined at pH 5.8 and room temperature using over 900 experimental restraints derived from two- and three-dimensional NMR experiments. The structure is comprised of a well-defined five-stranded beta-sheet with (+1, +1, +1, -4 alpha) topology. There is no helical region except for a single turn of 3(10) helix between the beta D and beta E strands. PsaE also exhibits a large unrestrained loop spanning residues 42-56. A comparison to known protein structures revealed similarity with the Src homology 3 (SH3) domain, a membrane-associated protein involved in signal transduction in eukaryotes. The match is remarkable as 47 of the alpha-carbons of PsaE can be superimposed onto those of the SH3 domain from chicken brain alpha spectrin with a root-mean-square deviation of 2.3 A. Although the amino acid sequences have low identity and the loops are different in both proteins, the topology of the beta-sheet and the 3(10) turn is conserved. SH3 domains from other sources show a similar structural homology. The structure of PsaE was used to suggest approaches for elucidating its roles within photosystem I. PMID- 8193120 TI - Structure around the cleavage site in the thrombin receptor determined by NMR spectroscopy. AB - NMR spectroscopic experiments were performed to study the structure of synthetic peptides identical to two extracellular regions of the human thrombin receptor. The smaller molecule, comprising 14 amino acids, was biologically active and was equivalent to the "tethered ligand" exposed after cleavage of the receptor by thrombin. The principal structural elements were two overlapping turns (amino acids 5-8 and 6-9), the second of which was stabilized by a hydrogen bond, 6CO 9NH. The five N-terminal residues, considered to be responsible for biological activity, were essentially unstructured. A second version of this peptide, biologically inactive due to the reversal of the two N-terminal amino acids, had a very similar structure. A longer peptide (23 amino acids) covering the proposed thrombin cleavage site was found to be more highly structured. The seven residues from Pro-2 to Arg5 (the N-terminal amino acid exposed after cleavage is taken as residue 1) formed a 3(10) helix which is not present in the shorter tethered ligand peptide. The structure is partially stabilized by a charged hydrogen bond between the side chains of Arg-1 and Asp-3. The overlapping turns observed in the shorter peptides could also be distinguished in the longer molecule. On the basis of the structure determined for the peptide which encompasses the cleavage site and the determined structure of thrombin, a model is postulated for the interaction of the thrombin receptor and the protease during activation. PMID- 8193121 TI - Structural determinants of high-affinity binding of ryanoids to the vertebrate skeletal muscle ryanodine receptor: a comparative molecular field analysis. AB - Ryanodine binds to specific membrane proteins, altering the calcium permeability of intracellular membranes. In this study 19 ryanoids were isolated or synthesized and the structures correlated to the strength of binding to vertebrate skeletal muscle ryanodine receptors. Global minima were determined by employment of molecular mechanics and dynamics augmented by systematic searching of conformational space. Overall, steric and electrostatic factors contribute about equally to the differences in the experimentally determined dissociation constants. The dominant electrostatic interaction is localized to a hydroxyl group in an apolar region of the molecule. The pyrrole and isopropyl groups located together at one pole of the molecule have the greatest effect on steric interactions between ligand and receptor. We suggest ryanodine binds to the receptor with the pyrrole and isopropyl groups buried deep inside a cleft in the protein. This arrangement places special importance on the conformation of the pyrrole and isopropyl groups. In contrast, the opposite pole appears to be positioned at the entrance of the binding pocket because bulky adducts placed in the 9 position of ryanodine alter binding minimally. For example, a fluorescent ryanodine adduct was synthesized which has a dissociation constant close to that of ryanodine. Detailed examination reveals subtle interactions between ryanoid and receptor. In many cases, the major factors altering the strength of binding were found to be conformational alterations in the molecule remote from the site of covalent modification. PMID- 8193122 TI - Fibronectin receptors from gram-positive bacteria: comparison of active sites. AB - Many parasitic bacteria express fibronectin binding proteins that are located on the cell surface. These proteins may act as adhesins and mediate the adherence of the microorganisms to fibronectin-containing host tissues. The ligand binding sites in the fibronectin receptor proteins from Gram-positive bacteria are composed of unique 37-48 amino acid long motifs that are repeated 3-4 times. We have now expressed the ligand binding sites of fibronectin receptors from Staphylococcus aureus, Streptococcus dysgalactiae (two receptors), and Streptococcus pyogenes as recombinant proteins. The purified recombinant proteins have the expected molecular weights as indicated by electrospray mass spectroscopy although they migrate abnormally on SDS-PAGE. Each recombinant protein effectively inhibited the binding of 125I-labeled intact fibronectin or the N-terminal fibronectin domain to Staphylococcus aureus, Streptococcus dysgalactiae, and Streptococcus pyogenes. The relative inhibitory potency of the different recombinant proteins was similar for all target bacteria and is reflected in their relative affinities for fibronectin. Synthetic peptides corresponding to the repeat units of the ligand binding site of the fibronectin receptor proteins were shown to inhibit the binding of the N-terminal fibronectin fragment to Streptococcus pyogenes cells. Together with amino acid sequence comparison, these data demonstrate that the repeat motif of the fibronectin receptor of Streptococcus pyogenes conforms to the consensus sequence previously reported for the Staphylococcus aureus receptor and to one of the Streptococcus dysgalactiae receptors (McGavin et al., 1993). PMID- 8193123 TI - Properties of human plasma lipid transfer protein in aqueous solution and at interfaces. AB - Human plasma lipid transfer protein (cholesteryl ester transfer protein) has been characterized for its solution and surface properties. The protein is monomeric in aqueous solution up to 0.62 g/L (11.7 microM) as demonstrated by sedimentation equilibrium. It binds to the surface of a lipid microemulsion having an average diameter of 26 nm made from triolein and egg yolk phosphatidylcholine, with an estimated dissociation constant 1.2 x 10(-8) M, and the maximum saturation binding level is 8 protein molecules per particle regardless of the presence of apolipoprotein A-I. Circular dichroism measurement indicated that the protein in solution is predominantly in the beta-sheet/beta-turn conformation with some alpha-helix, and this profile does not undergo drastic change by its binding to the lipid surface. The analysis of the behavior of the protein in its monomolecular layer at the air-buffer interface indicated that it is also monomeric at the interface. LTP molecules occupied the same area per amino acid as other apolipoproteins in the monolayer but had a higher collapse pressure of its monolayer (18 dyn/cm), and the protein stayed at the interface even after the overcompressing monolayer far beyond the collapsing pressure up to 40 dyn/cm. PMID- 8193124 TI - Regulation and phase equilibria of membrane lipids from Bacillus megaterium and Acholeplasma laidlawii strain A containing methyl-branched acyl chains. AB - Phosphatidylethanolamine (PE) was isolated from Bacillus megaterium grown at 20 and 55 degrees C (PE-20 and PE-55). Iso and anteiso methyl-branched, saturated acyl chains are predominant in B. megaterium, and the value of the molar ratio of iso/anteiso acyl chains is more than 20-fold higher in PE-55 than in PE-20. Moreover, about 21 mol% of the acyl chains of PE-20 are monounsaturated. The phase equilibria differ between the two PE preparations: (1) PE-20 is more prone to form reversed nonlamellar phases than PE-55; (2) PE-20 forms both reversed cubic (I2) and reversed hexagonal (H(II)) phases while PE-55 forms only an HII phase; and (3) the lamellar liquid-crystalline (L alpha) phase of PE-20 takes up about 70% more water than the L alpha phase of PE-55. These differences can be explained by the differences in the acyl chain composition. When the growth temperature is raised, PE molecules with a reduced tendency to form nonlamellar phases are probably synthesized by B. megaterium in order to counteract the bilayer destabilizing effect of the temperature. The regulation of the acyl chain composition is not needed in order to regulate the temperature for the transition between gel/crystalline and L alpha phases of the membrane lipids. Acholeplasma laidlawii strain A-EF22 was grown at 37 degrees C on 15-(1,1,1(-2) H3)methylhexadecanoic acid, 14-(1,1,1(-2)H3)methylhexadecanoic acid or 13-(1,1,1( 2)H3)methylhexadecanoic acid, and these acids constituted 84-89 mol% of the acyl chains in the membrane lipids. The molar ratio between the two dominating lipids, monoglucosyldiacylglycerol (MGLcDAG) and diglucosyldiacylglycerol (DGlcDAG), decreased, and the molar fraction of the anionic lipids increased, when the methyl branch was moved from position 15 to position 13. Concomitantly, the order of the methyl branch increased in cells as well as in total lipid extracts. The phase equilibria of total lipid extracts (neutral lipids removed) were studied with 20 wt % of water, and HII and I2 phases were formed above 63-67 degrees C. These results indicate that the regulation of the polar head-group composition compensates for the difference in acyl chain packing introduced into the bilayer by the three branched-chain fatty acids. The regulation of the polar head-group composition of the A. laidlawii lipids cannot regulate the temperature for the transition between gel/crystalline and L alpha phases of the lipids, i.e. the transition to fluid acyl chains.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8193125 TI - Structure and function in rhodopsin. 7. Point mutations associated with autosomal dominant retinitis pigmentosa. AB - Autosomal dominant retinitis pigmentosa (ADRP) is a hereditary form of retinitis pigmentosa which accounts for about 15% of all types of the latter disease. Recently, close to 50 mutations, mostly point mutations, have been identified in the rhodopsin gene in ADRP patients. We have introduced these mutations in the synthetic bovine rhodopsin gene and herein report on the expression of the mutant genes in COS-1 cells and studies in vitro of the properties of the expressed opsins. The mutant phenotypes fall into three classes: Class I mutants are expressed in COS-1 cells at wild-type levels, form the normal rhodopsin chromophore with 11-cis-retinal, and are transported to the cell surface. However, on illumination, they activate transducin inefficiently. Class II mutants remain in the endoplasmic reticulum and do not bind 11-cis-retinal to form the chromophore. Class III mutants are expressed at low levels and form rhodopsin chromophore only poorly. They also remain in the endoplasmic reticulum and, as expected, show high mannose glycosylation. Nearly all of the mutants studied show abnormal sensitivity to light compared to the wild type, and they activate transducin less efficiently. We conclude that the majority of the ADRP mutants have folding defects. PMID- 8193126 TI - Determination of internuclear distances and the orientation of functional groups by solid-state NMR: rotational resonance study of the conformation of retinal in bacteriorhodopsin. AB - We have used a new solid-state NMR technique--rotational resonance--to determine both internuclear distances and the relative orientations of chemical groups (dihedral angles) in retinal bound to bacteriorhodopsin (bR) and in retinoic acid model compounds. By matching the rotational resonance condition (delta = n omega r/2 pi, where delta is the difference in isotropic chemical shifts for two dipolar coupled spins, omega r/2 pi is the mechanical rotational frequency of the sample in the MAS experiment, and n is a small integer denoting the order of the resonance), we selectively reintroduce the dipolar coupling and enhance the rate of magnetization exchange. Spectroscopic data and theoretical simulations of the magnetization exchange trajectories for the 8,18-13C dipolar coupled pair in retinoic acid model compounds, crystallized in both the 6-s-cis and 6-s-trans forms, indicate that an accurate determination of the internuclear distance is possible. For the n = 1 resonance we find the distance determination to be reasonably independent of the relative orientation of the groups. In contrast, for the n = 2 resonance, there is a more pronounced dependence on the relative orientation of the groups which permits an estimate of the angle around the 6-s bond for the cis and trans forms to be 42 +/- 5 degrees and 90 +/- 10 degrees, respectively, in good agreement with crystallography. In bR we demonstrate that the 8-13C-18-13C distance is 4.1 A and the average 8-13C-16-13C/8-13C-17-13C distance is 3.3-3.5 A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193127 TI - Site-directed photosystem II mutants with perturbed oxygen-evolving properties. 1. Instability or inefficient assembly of the manganese cluster in vivo. AB - Several site-directed photosystem II mutants with substitutions at Asp-170 of the D1 polypeptide were characterized by noninvasive methods in vivo. In several mutants, including some that evolve oxygen, a significant fraction of photosystem II reaction centers are shown to lack photooxidizable Mn ions. In this fraction of reaction centers, either the high-affinity site from which Mn ions rapidly reduce the oxidized secondary electron donor, YZ+, is devoid of Mn ions or the Mn ion(s) bound at this site are unable to reduce YZ+. It is concluded that the Mn clusters in these mutants are unstable or are assembled inefficiently in vivo. Mutants were constructed in the unicellular cyanobacterium Synechocystis sp. PCC 6803. The in vivo characterization procedures employed in this study involved measuring changes in the yield of variable chlorophyll a fluorescence following a saturating flash or brief illumination given in the presence of the electron transfer inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea, or following each of a series of saturating flashes given in the absence of this inhibitor. These procedures are easily applied to mutants that evolve little or no oxygen, facilitate the characterization of mutants with labile oxygen-evolving complexes, permit photosystem II isolation efforts to be concentrated on mutants having the stablest Mn clusters, and guide systematic spectroscopic studies of isolated photosystem II particles to mutants of particular interest. PMID- 8193128 TI - Site-directed photosystem II mutants with perturbed oxygen-evolving properties. 2. Increased binding or photooxidation of manganese in the absence of the extrinsic 33-kDa polypeptide in vivo. AB - Several site-directed photosystem II mutants with substitutions at Asp-170 or in the carboxyterminal region of the D1 polypeptide were characterized in vivo in the absence of the extrinsic 33-kDa polypeptide. Site-directed mutations were constructed in the cyanobacterium Synechocystis sp. PCC 6803. The 33-kDa polypeptide was removed by insertional inactivation of the Synechocystis psbO gene. Mutants were characterized by measuring changes in the yield of variable chlorophyll a fluorescence following a saturating flash or brief illumination in the presence of an electron-transfer inhibitor or following each of a series of saturating flashes in the absence of inhibitor [Chu, H.-A., Nguyen, A. P., & Debus, R. J. (1994) Biochemistry (preceding paper in this issue)]. In the presence of the extrinsic 33-kDa polypeptide, many site-directed mutants contained a significant fraction of photosystem II reaction centers that lacked photooxidizable Mn ions. This fraction decreased dramatically in the absence of the extrinsic 33-kDa polypeptide, even in mutants having a significantly perturbed high-affinity Mn binding site (e.g., in the mutants D170A and D170T). These results show that, in vivo, the extrinsic 33-kDa polypeptide directly or indirectly governs the occupancy of the high-affinity Mn binding site by Mn ions or the ability of bound Mn ions to reduce YZ+. PMID- 8193129 TI - Modeling compact denatured states of proteins. AB - We propose a model for the conformations of compact denatured states of globular proteins: that they are broad ensembles of chain backbone conformations that involve common localized hydrophobic clustering and helical contacts, depending on the amino acid sequence. We construct representative ensembles for chain lengths up to 136 monomers on three-dimensional cubic lattices using the "hydrophobic zippers" method (Fiebig & Dill, 1993). We find that model conformations with radii of gyration about 20% larger than native conformations commonly have bimodal distributions of P(r), of the pairwise interatomic distances, r, and Kratky plots in agreement with recent small-angle X-ray scattering (Sosnick & Trewhella, 1992; Flanagan et al., 1992; Kataoka et al., 1993; Flanagan et al., 1993) experiments on three different proteins. We also find that the lattice model of the Shortle 1-136 fragment of staphylococcal nuclease does not appear capable of forming a single hydrophobic core by hydrophobic zippering, consistent with experiments. PMID- 8193130 TI - Effects of base composition on the negative cooperativity and binding mode transitions of Escherichia coli SSB-single-stranded DNA complexes. AB - We have examined the ability of the Escherichia coli single-stranded DNA binding protein (SSB) tetramer to form its different binding modes on poly(dC), poly(U), and poly(A) over a range of NaCl and NaF concentrations for comparison with previous studies with poly(dT). In reverse titrations with poly(U) and poly(A) at 25 degrees C, pH 8.1, SSB forms all four binding modes previously observed with poly(dT), namely, (SSB)35, (SSB)40, (SSB)56, and (SSB)65, where the subscript denotes the site size (i.e., the average number of nucleotides occluded per SSB tetramer). As with poly(dT), the low site size modes are favored at low monovalent salt concentration (< 10 mM), whereas increasing salt concentration facilitates the transitions to the higher site size modes. Surprisingly, SSB does not form a stable (SSB)35 complex on poly(dC), even at 1 mM NaCl; rather, the (SSB)56 mode is formed under these conditions. Upon raising the [NaCl], the (SSB)56 complex undergoes a transition to the (SSB)65 complex (transition midpoint, 40 mM NaCl). On the basis of studies with dC(pC)34, dT(pT)34, and dA(pA)34, the inability of the SSB tetramer to form the (SSB)35 complex with poly(dC) is due mainly to a much lower degree of negative cooperativity for binding oligodeoxycytidylates to the SSB tetramer. At low salt concentration, the negative cooperativity parameter, sigma 35, is lowest for dA(pA)34, intermediate for dT(pT)34, and highest for dC(pC)34, indicating that it is most difficult to saturate the SSB tetramer with two molecules of dA(pA)34. We have also measured the equilibrium constants for binding the oligodeoxynucleotides dC(pC)34, dC(pC)69, dA(pA)34, and dA(pA)69 as a function of [NaCl] and [NaBr] and find that the salt dependencies of these oligonucleotides are dependent upon base composition. These studies also indicate that ion binding accompanies formation of these SSB-ss-DNA complexes, although there is a net release of ions upon formation of the complex. This influence of both salt concentration and base composition indicates that both electrostatic and nonelectrostatic factors contribute to the negative cooperativity associated with ss-DNA binding to the SSB tetramer. PMID- 8193131 TI - Mapping critical residues in eukaryotic DNA-binding proteins: a plasmid-based genetic selection strategy with application to the Oct-2 POU motif. AB - Discrimination between allowed and disallowed amino acid substitutions provides a powerful method for analysis of protein structure and function. Site-directed mutagenesis allows specific hypotheses to be tested, but its systematic application to entire structural motifs is inefficient. This limitation may be overcome by genetic selection, which allows rapid scoring of thousands of randomly (or pseudorandomly) generated mutants. To facilitate structural dissection of DNA-binding proteins, we have designed two generally applicable bacterial selection systems: pPLUS selects for the ability of a protein to bind to a user-defined DNA sequence, whereas pMINUS selects against such binding. Complementary positive and negative selections allow rapid mapping of critical residues. To test and calibrate the systems, we have investigated the bipartite POU domain of the human B-cell-specific transcription factor Oct-2. (i) An invariant residue (Asn347) in the DNA-recognition helix of the POU-specific homeodomain (POUHD) was substituted by each of the 19 other possible amino acids. The mutant proteins each exhibited decreased specific DNA binding as defined in vivo by genetic selection and in vitro by gel retardation; relative affinities correlate with phenotypes in the positive and negative selection systems. An essential role for Asn347 in wild-type POUHD-DNA recognition is consistent with homologous Asn-adenine interactions in cocrystal structures of canonical homeodomains. (ii) Extension of pPLUS/pMINUS selection to the POU-specific subdomain (POUs) is demonstrated by analysis of mutations in its putative helix turn-helix (HTH) element.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193132 TI - Deletion mutants of poly(ADP-ribose) polymerase support a model of cyclic association and dissociation of enzyme from DNA ends during DNA repair. AB - With an in vitro DNA repair system, Satoh and Lindah [(1992) Nature 356, 356-358] demonstrated that unmodified poly(ADP-ribose) polymerase (PADPRP) binds to radiation-damaged DNA and inhibits repair in the absence of NAD. However, in the presence of NAD, PADPRP undergoes automodification and the DNA is repaired. It was hypothesized that PADPRP cycles between an unmodified form, which protects DNA breaks, and an automodified form, which is released from DNA, thereby allowing access to repair enzymes. We have now tested this model with bacterially expressed mutants of PADPRP with deletions in the three major functional domains of the enzyme [Cherney, B. W., Chaudry, B., Bhatia, K., Butt, T. R., & Smulson, M. E. (1991) Biochemistry 30, 10420-10427]. Deletion mutants with an intact amino terminal DNA-binding domain, and therefore capable of binding to DNA strand breaks in the in vitro assay, inhibited repair; however, whether the deletion was in the NAD-binding, active site domain or the automodification domain, the inhibition of repair exerted by these mutant proteins was not alleviated by NAD. A PADPRP mutant with a deletion in the DNA-binding domain did not inhibit DNA repair. Thus, the behavior of these PADPRP deletion mutants is consistent with the model proposed earlier. The model was also supported by experiments with Manley extracts of HeLa cells stably transfected with a PADPRP antisense RNA construct. Extracts of cells induced to express antisense RNA did not markedly inhibit in vitro DNA repair, nor did the addition of NAD influence the assay. In contrast, noninduced cell extracts inhibited repair and inhibition was alleviated by NAD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193133 TI - Inhibition of Klenow fragment DNA polymerase on double-helical templates by oligonucleotide-directed triple-helix formation. AB - We have examined the capacity of oligonucleotide-directed triple helices to block the progress of primer extension by DNA polymerase. Occupancy of the major groove of a double-helical DNA substrate obstructed Klenow fragment progress at sites that map near the proximal boundary between duplex and triplex. Among a family of related third-strand oligonucleotides that all stably occupied the target duplex in the absence of polymerase, those forming longer triplexes were more effective polymerase inhibitors than shorter complexes. Kinetic analysis revealed that the triple-helical complex provided an effective blockade for times of at least 20 min. These observations provide the basis for considering and further dissecting repair DNA polymerase function and mechanism by using various defined local three stranded DNA structures as probes. PMID- 8193134 TI - Sequence specificity of (cyanomorpholino)adriamycin adducts in human cells. AB - The highly reiterated alpha DNA tandem repeat was extracted from HeLa cells incubated with (cyanomorpholino)adriamycin (CMA) using mild techniques and subsequently probed for drug adducts by exonuclease III. The sequence specificity of the CMA-induced blockages was compared with that for blockages induced on the same DNA fragment when reacted in vitro. The sequence specificity of the drug induced blockages was the same on both the isolated and the intact cell alpha DNA templates, with blockages predominantly associated with GpG sequences on either strand of the DNA. PMID- 8193135 TI - Modulation of the oxidation-reduction potential of the flavin in lipoamide dehydrogenase from Escherichia coli by alteration of a nearby charged residue, K53R. AB - The epsilon-amino group of a lysine residue occupies a position within bonding distance of the flavin N5 and the bound NADPH pyridinium C4' in glutathione reductase, and it has been suggested that this positive charge influences the redox potential of the FAD [Pai & Schulz (1983) J. Biol. Chem. 258, 1752]. A conserved lysine residue occupies a similar position in lipoamide dehydrogenase. This residue has been replaced by an arginine in lipoamide dehydrogenase from Escherichia coli to give K53R. The spectral and redox properties of the FAD in K53R as well as the interaction of the flavin with bound NAD+ are profoundly affected by the change. K53R does not catalyze either the dihydrolipoamide-NAD+ or the NADH-lipoamide reactions except at very low concentrations of the reducing substrate. The absorbance spectrum of K53R in the visible and near-ultraviolet is little changed from that of wild-type enzyme, but in contrast, the spectrum of K53R is sensitive to pH with an apparent pKa = 7.0. Unlike the wild-type enzyme, the binding of beta-NAD+ to K53R alters the spectrum and indicates an apparent Kd = 7.0 microM at pH 7.6. The flavin fluorescence is partially quenched, and the visible and near-ultraviolet circular dichroism spectrum is changed by beta-NAD+. K53R is extensively reduced (mostly EH4) by 2 equiv of dihydrolipoamide/FAD while the wild-type enzyme is only partially reduced (mostly EH2). The rate of this reduction is lowered by approximately 3-fold relative to the wild-type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193136 TI - Ligand binding to anti-fluorescyl antibodies: stability of the antigen binding site. AB - The problem of protein stability is addressed with spectroscopic studies of equilibrium and kinetic properties of the binding of fluorescein to high-affinity monoclonal anti-fluorescyl antibodies (Mab 4-4-20), Fab fragments, and single chain antibodies (SCA). SCA molecules contain only the variable domains of the antibody and an amino acid linker. The influence of glycerol on the antigen binding reaction is studied by circular dichroism, fluorescence, and absorption spectroscopy. The presence of glycerol in the solvent lowers the affinity of SCA for the ligand drastically, and the affinity even decreases toward lower temperatures. This effect is not observed in Fab and Mab. Analysis of the temperature jump kinetics shows that the dissociation reaction can be modeled as a two-state transition. The CD spectra indicate that the domain structure of the SCA remains unaltered in the presence of glycerol. Therefore, it is concluded that glycerol promotes the dissociation of the two variable domains of SCA. In Fab and Mab, the constant domains provide additional stabilization of the molecular structure at the antigen binding site. PMID- 8193137 TI - Role of glycosylation in the biosynthesis and activity of rabbit testicular angiotensin-converting enzyme. AB - Angiotensin-converting enzyme (ACE) is a type I glycoprotein anchored in the plasma membrane by a hydrophobic domain near its carboxyl terminus. The enzymatically active extracellular domain of ACE is slowly released from the cell by cleavage-removal of its membrane-anchoring carboxyl-terminal region. In the present study, we investigated the role of N- and O-glycosylation in intracellular transport and extracellular cleavage-secretion of rabbit testicular ACE. For ACE expression, we used an in vitro translation system, a permanently transfected mouse cell line, and human and Chinese hamster cells transiently transfected with vaccinia virus-T7 RNA polymerase-driven expression vectors. Sugar modifications of ACE were analyzed by testing its sensitivity to specific glycosidases. Cellular protein glycosylation was inhibited by using chemical inhibitors and a mutant cell line defective in protein glycosylation. Our experiments demonstrated that newly synthesized ACE acquires both N- and O-linked sugars before its cleavage-secretion and complete blockage of glycosylation results in rapid intracellular turnover of underglycosylated ACE. However, ACE synthesized without N-linked complex sugars and O-linked sugars can undergo normal transport and cleavage-secretion, and the underglycosylated protein is enzymatically active. PMID- 8193138 TI - Increased cytotoxicity of interleukin 2-pseudomonas exotoxin (IL2-PE) chimeric proteins containing a targeting signal for lysosomal membranes. AB - IL2-PE40 is a chimeric protein composed of human interleukin 2 (IL2) genetically fused to the amino terminus of a truncated form of pseudomonas exotoxin lacking its cell recognition domain (PE40). IL2-PE40 is extremely cytotoxic to IL2 receptor positive cells. This chimeric protein was found to be an effective and selective immunosuppressive agent for IL2 receptor targeted therapy in many models of disorders of the immune response where activated T-cells play a crucial role. In an attempt to produce an improved IL2-PE40 chimeric protein, we constructed new IL2-PE derivatives. This was done by inserting defined DNA sequences within the chimeric gene encoding IL2-PE40. Inserted sequences represent motifs of other proteins known to be targeted and/or sorted to specific compartments inside or outside the cell. One of the proteins, IL2-PE40(LAP+DUP), containing a targeted signal for lysosomal membrane, was 2-3-fold more active than IL2-PE40. The insertion of the LAP sequence also increased the cytotoxicity of another IL2-PE derivative, IL2-PE664Glu. Our results suggest that a selective targeting of IL2-PE chimeric proteins to lysosomes may enable the proteins to reach the cytosol more efficiently, thus improving its specific cytotoxicity. The LAP (lysosomal alkaline phosphatase) sequence may be used as a common motif for increasing the cytotoxicity of other chimeric proteins to be used for targeted immunotherapy. PMID- 8193139 TI - Interaction of tubulin and microtubule proteins with vanadate oligomers. AB - Microtubule assembly is known to be regulated by the phosphorylation of microtubule-associated proteins (MAPs), and is thus sensitive to phosphatase inhibitors. We have investigated the direct interaction between phosphatase inhibitors (vanadate, sodium fluoride, and okadaic acid) and microtubule proteins. Vanadate self-assembles into oligomers, primarily dimer, tetramer, and decamer in 0.1 M Pipes, pH 6.9. Oligomer concentrations and their direct binding to tubulin and MAPs were determined by 51V NMR. The assembly of microtubule protein (MTP) is strongly inhibited by decavanadate binding to MAPs and only weakly inhibited by tetravanadate binding to MAPs. Decavanadate will inhibit both MAP2 and tau-induced assembly. Decavanadate binds to MAP2 at 26 sites [Ka > or = (1.0-1.3) x 10(5) M-1]. The mechanism appears to involve competitive binding to MAPs, presumably at or near the microtubule binding domains, and reduced affinity for microtubules. The assembly of MAP-free, phosphocellulose-purified tubulin (PC tubulin) is only weakly inhibited by decavanadate, although decavanadate binds to tubulin at four independent sites (Ka > or = 1.0 x 10(5) M-1). Monomeric vanadate, a strong phosphatase inhibitor, does not interact with tubulin or MAPs, and thus does not bind to the exchangeable nucleotide binding site on tubulin. Sodium fluoride stimulates both PC-tubulin and MTP assembly by a nonspecific effect, probably involving water structure formation. Wyman analysis suggests an absence of direct or specific binding to tubulin (d ln K/d ln [NaF] = 0.214). NaCl is nearly as effective in promoting assembly of PC-tubulin, but inhibits MTP assembly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193140 TI - The colchicine-induced GTPase activity of tubulin: state of the product. Activation by microtubule-promoting cosolvents. AB - Colchicine induces a weak assembly-independent GTPase activity in calf brain tubulin [David-Pfeuty, T., Erickson, H. P., & Pantaloni, D. (1977) Proc. Natl. Acad. Sci. U.S.A. 74, 5372-5376; Andreu, J. M., & Timasheff, S. N. (1981) Arch. Biochem. Biophys. 211, 151-157]. Kinetic analysis shows a turnover number of 2 x 10(-4) s-1 in 0.01 M sodium phosphate and 4 mM MgCl2, pH 7.0, with an apparent Km for GTP of 10 microM. This activity, which requires Mg2+ ions and attains a plateau at 4 mM MgCl2, is independent of pH over the pH range of 6.6-7.4. This GTPase activity was induced by all colchicine analogues that contain rings A and C (or C'), the strength varying in a manner parallel to the free energy of binding of the ligand. The specific GTPase activity was found to be independent of the tubulin-colchicine complex concentration over the range of 2-20 microM. Sedimentation velocity examination of the product of the reaction showed that GDP tubulin-colchicine generated by hydrolysis of the E-site GTP was indistinguishable from that produced by nucleotide exchange at the site, the protein assuming the "curved" conformation in both cases. Steady-state kinetic analysis in the presence of high concentrations of microtubule-inducing cosolvent additives revealed an increase in kcat/Km of up to 1 order of magnitude that followed the order poly(ethylene glycol) 6000 (PEG-6000 > PEG-1000 = 2-methyl-2,4 pentanediol > sucrose > L-glutamate > glycerol = PEG-200 > betaine, with no apparent change in Km.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193141 TI - Cosolvent modulation of the tubulin-colchicine GTPase-activating conformational change: strength of the enzymatic activity. AB - The locus of action of cosolvent additives in the activation of the tubulin colchicine GTPase was investigated. The GDP off rates were slowed down by the cosolvents in a manner that parallels their specific viscosities, indicating that diffusion-controlled release of GDP may be rate-limiting under the conditions of these studies. Yet, the net effect of cosolvents was to increase the overall rate of GTP hydrolysis. Pre-steady-state kinetics of liganded tubulin in the presence of 1%, w/v, poly(ethylene glycol) 6000 (PEG-6000) exhibited a burst of inorganic phosphate release indicating that the cosolvents act at an early step in the process. A similar conclusion was drawn from measurements of the activation energy (Ea) of the reaction, which showed that 3.4 M glycerol decreased the value of Ea to 10.6 kcal mol-1 from 17.3 kcal mol-1 in its absence. The observed difference in apparent binding free energies of the colchicine analogues allo colchicine (ALLO) and 2-methoxy-5-(2,3,4-trimethoxyphenyl)-2,4,6-cycloheptatrien 1-one (MTC, or des-ring B colchicine), when measured by fluorescence and enzyme activity titrations, identified the presence of a GTPase-activating protein conformational transition subsequent to the physicochemical binding of the ligands. The decrease of the apparent binding constant measured by enzyme activity in dilute buffer relative to that measured by fluorescence [for ALLO, Kb(fluor) = 1.46 x 10(6) M-1; Kb(enz act) = 1.1 x 10(5) M-1] yielded the value of the enzyme-activating conformational transition constant, K3 = 0.08.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193142 TI - ATP binding in peptide synthetases: determination of contact sites of the adenine moiety by photoaffinity labeling of tyrocidine synthetase 1 with 2-azidoadenosine triphosphate. AB - Characterization of the nucleotide binding domain in peptide synthetases was approached by photoaffinity labeling of tyrocidine synthetase 1 (TY1) with 2 azidoadenosine triphosphate (2-azido-ATP). Exposure of TY1 in the presence of photolabel to irradiation with ultraviolet light resulted in a time-dependent covalent modification of the enzyme with a concomitant loss of catalytic activity. Inactivation was not observed if incubation was performed in the absence of either light or the nucleotide analogue. Specificity of labeling was indicated by the ability of 2-azido-ATP to serve as a substrate in the amino acid activation reaction. The modified protein was subjected to tryptic digestion, and the fragments labeled by the nucleotide analogue were purified by reverse-phase high-performance liquid chromatography. Sequence analysis identified three tryptic peptides corresponding to residues G373-K384, W405-R416, and L483-K494, derived from the N-terminal half of the TY1 sequence. As this region shows similarity to strongly conserved regions in other peptide synthetases and acyl CoA synthetases, it is considered to be the region catalyzing aminoacyl adenylate formation. The identified sequences appear to define components of the nucleotide binding domain found in close proximity to the adenine ring in ATP. Conservation of primary structure and homology to other carboxyl-activating enzymes of this superfamily, including peptide synthetases, insect luciferases, and acyl-CoA synthetases, is discussed. PMID- 8193143 TI - The active center of a mammalian alpha-amylase. Structure of the complex of a pancreatic alpha-amylase with a carbohydrate inhibitor refined to 2.2-A resolution. AB - An X-ray structure analysis of a crystal of pig pancreatic alpha-amylase (EC 3.2.1.1) that was soaked with acarbose (a pseudotetrasaccharide alpha-amylase inhibitor) showed electron density corresponding to five fully occupied subsites in the active site. The crystal structure was refined to an R-factor of 15.3%, with a root mean square deviation in bond distances of 0.015 A. The model includes all 496 residues of the enzyme, one calcium ion, one chloride ion, 393 water molecules, and five bound sugar rings. The pseudodisaccharide acarviosine that is the essential structural unit responsible for the activity of all inhibitors of the acarbose type was located at the catalytic center. The carboxylic oxygens of the catalytically competent residues Glu233 and Asp300 form hydrogen bonds with the "glycosidic" NH group of the acarviosine group. The third residue of the catalytic triad Asp197 is located on the opposite side of the inhibitor binding cleft with one of its carbonyl oxygens at a 3.3-A distance from the anomeric carbon C-1 of the inhibitor center. Binding of inhibitor induces structural changes at the active site of the enzyme. A loop region between residues 304 and 309 moves in toward the bound saccharide, the resulting maximal mainchain movement being 5 A for His305. The side chain of residue Asp300 rotates upon inhibitor binding and makes strong van der Waals contacts with the imidazole ring of His299. Four histidine residues (His101, His201, His299, and His305) are found to be hydrogen-bonded with the inhibitor. Many protein-inhibitor hydrogen bond interactions are observed in the complex structure, as is clear hydrophobic stacking of aromatic residues with the inhibitor surface. The chloride activator ion and structural calcium ion are hydrogen-bonded via their ligands and water molecules to the catalytic residues. PMID- 8193144 TI - Catalytic metal ion binding in enolase: the crystal structure of an enolase-Mn2+ phosphonoacetohydroxamate complex at 2.4-A resolution. AB - Enolase, a glycolytic enzyme that catalyzes the dehydration of 2-phospho-D glycerate (PGA) to form phosphoenolpyruvate (PEP), requires two divalent metal ions per active site for activity. The first metal ion, traditionally referred to as "conformational", binds in a high-affinity site I. The second metal ion, "catalytic", binds in site II only in the presence of a substrate or substrate analogue and with much lower affinity for the physiological cofactor Mg2+. While the high-affinity site has been well characterized, the position of the lower affinity site has not been established so far. Here, we report the structure of the quaternary complex between enolase, the transition-state analogue phosphonoacetohydroxamate (PhAH), and two Mn2+ ions. The structure has been refined by using 16 561 reflections with F/sigma (F) > or = 3 to an R = 0.165 with average deviations of bond lengths and bond angles from ideal values of 0.013 A and 3.1 degrees, respectively. The "catalytic" metal ion is coordinated to two oxygen atoms of the phosphono moiety of PhAH and to the carbonyl oxygen of Gly37. Most likely, disordered water molecules complement its coordination sphere. The interaction with the site II metal ion must stabilize negative charge on the phosphate group and produce electron withdrawal from carbon 2 of the substrate, facilitating proton abstraction from carbon 2, the rate-limiting step in the catalytic process. The Gly37 residue is located in the flexible loop Ser36 His43, which assumes an "open" conformation in the absence of substrate and a "closed" conformation in the presence of a substrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193145 TI - Structure of rabbit muscle pyruvate kinase complexed with Mn2+, K+, and pyruvate. AB - The molecular structure of rabbit muscle pyruvate kinase, crystallized as a complex with Mn2+, K+, and pyruvate, has been solved to 2.9-A resolution. Crystals employed in the investigation belonged to the space group P1 and had unit cell dimensions a = 83.6 A, b = 109.9 A, c = 146.8 A, alpha = 94.9 degrees, beta = 93.6 degrees, and gamma = 112.3 degrees. There were two tetramers in the asymmetric unit. The structure was solved by molecular replacement, using as the search model the coordinates of the tetramer of pyruvate kinase from cat muscle [Muirhead, H., Claydon, D. A., Barford, D., Lorimer, C. G., Fothergill-Gilmore, L. A., Schiltz, E., & Schmitt, W. (1986) EMBO J.5, 475-481]. The amino acid sequence derived from the cDNA coding for the enzyme from rabbit muscle was fit to the electron density. The rabbit and cat muscle enzymes have approximately 94% sequence identity, and the folding patterns are expected to be nearly identical. There are, however, three regions where the topological models of the cat and rabbit pyruvate kinases differ. Mn2+ coordinates to the protein through the carboxylate side chains of Glu 271 and Asp 295. These two residues are strictly conserved in all known pyruvate kinases. In addition, the density for Mn2+ is connected to that of pyruvate, consistent with chelation through a carboxylate oxygen and the carbonyl oxygen of the substrate. The epsilon-NH2 of Lys 269 and the OH of Thr 327 lie on either side of the methyl group of bound pyruvate. Spherical electron density, assigned to K+, is located within a well-defined pocket of four oxygen ligands contributed by the carbonyl oxygen of Thr 113, O gamma of Ser 76, O delta 1 of Asn 74, and O delta 2 of Asp 112. The interaction of Asp 112 with the side chains of Lys 269 and Arg 72 may mediate, indirectly, monovalent cation effects on activity. PMID- 8193146 TI - Sulfur-containing cobalamins: X-ray absorption spectroscopic characterization. AB - Sulfur-containing cobalamins are thought to have a special role in the intracellular conversion of cyanocobalamin to its coenzyme forms through a Co(I) intermediate. Glutathionylcobalamin is especially interesting as a possible precursor of cobalamin coenzymes [Wagner et al. (1969) Ann. N.Y. Acad. Sci. 112, 580; Pezacka et al. (1990) Biochem. Biophys. Res. Commun. 169, 443]. Recent NMR data [Brown et al. (1993) Biochemistry 32, 8421] strongly support the hypothesis that glutathione coordinates ito the cobalt through the sulfur atom in glutathionylcobalamin. In this study three-sulfur containing cobalamin derivatives (glutathionylcobalamin, sulfitocobalamin, and cysteinylcobalamin) have been characterized by X-ray absorption spectroscopy. We give evidence for the sulfur coordination in these compounds and present the corresponding structural information. The Co-Neq distances are also distances in the sulfur containing cobalamins are very close to one another (1.90 +/- 0.01 A). The Co-S and Co-Nax distances are also similar (Co-S: 2.28-2.35 A and Co-Nax: 2.13-2.16 A) and in the expected range. The X-ray edge positions for the sulfur derivatives shift to lower energies with respect to cyanocobalamin. This indicates strong electron donation from the sulfur to the cobalt and suggests that the effective charge on the cobalt ion in sulfur cobalamins is largely reduced from +3. PMID- 8193147 TI - Solution 1H NMR determination of secondary structure for the three-iron form of ferredoxin from the hyperthermophilic archaeon Pyrococcus furiosus. AB - Two-dimensional 1H NMR data have been used to make sequence-specific assignments and define the secondary structure of the three-iron form of the oxidized ferredoxin, Fd, from the hyperthermophilic archaeon Pyrococcus furiosus, Pf. Signals for at least some protons were located for 65 of the 66 amino acids in the sequence, in spite of the paramagnetic (S = 1/2) ground state, but not all could be assigned. Unassigned and missing signals could be qualitatively correlated with the expected proximity of the protons to the paramagnetic cluster. The secondary structure was deduced from qualitative analysis of the 2D nuclear Overhauser effect, which identified two antiparallel beta-sheets, one triple-stranded including Ala1-Ser5, Val39-Glu41, and Thr62-Ala66, and one double stranded consisting of Glu26-Asn28 and Lys32-Glu34, as well as an alpha-helix involving Glu43-Glu54. Three tight type I turns are located at residues Asp7 Thr10, Pro22-Phe25, and Asp29-Gly31. Comparison with the crystal structure of Desulfovibrio gigas, Dg, Fd (Kissinger et al., 1991) reveals a very similar folding topology, although several secondary structural elements are extended in Pf relative to Dg Fd. Thus the beta-sheet involving the two termini is expanded to include the two terminal residues and incorporates a third strand from the internal loop that is lengthened by several insertions in Pf relative to Dg Fd. The double-stranded beta-sheet in the interior of Pf Fd is lengthened slightly due to a much tighter type I turn between the two strands. The helix near the C terminus is three residues longer in Pf than in Dg Fd, as well as being shifted toward the N-terminus. The disulfide link between the two nonligating Cys residues (Cys21 and Cys48) is conserved in Pf Fd, but the link near the C terminus is in the middle of the long alpha-helix in Pf Fd, instead of at the N terminus of the helix as in Dg Fd. The extensions of the beta-sheets and alpha helix increase the number of main-chain hydrogen bonds in Pf Fd by approximately 8 relative to those in Dg Fd and likely contribute to its remarkable thermostability (it is unaffected by anaerobic incubation at 95 degrees C for 24 h).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8193148 TI - Rotational resonance NMR determination of intra- and intermolecular distance constraints in dipalmitoylphosphatidylcholine bilayers. AB - Rotational resonance (RR) NMR methods are explored for determining intramolecular and intermolecular distances between 13C-labeled sites in membrane bilayers. Specific 13C labels have been incorporated into dipalmitoylphosphatidylcholine (DPPC) and a hydrophobic peptide corresponding to the transmembrane domain of human glycophorin A. The exchange of magnetization between these labels in the RR NMR experiment can be related to their internuclear separation. Intramolecular magnetization exchange rates have been measured between 13C labels incorporated at the 1-position of the sn-1 acyl chain (1-[1-13C]) and the 2-position of the sn 2 acyl chain (2-[2-13C]) of DPPC. These positions are 5.3-5.5 A apart in the crystal structure of dimyristoylphosphatidylcholine (DMPC), but are estimated to be 4.5-5.0 A apart in DPPC below the subphase transition temperature. These results are consistent with a smaller axial displacement between the sn-1 and sn 2 acyl chains than the approximately 3.6-A displacement observed in the DMPC crystal structure. Intermolecular magnetization transfer rates have been measured between 1,2-[2-13C]DPPC and 2-[1,13C]DPPC and between 1,2-[1-13C]DPPC and 2-[2 13C]DPPC. In addition, intermolecular magnetization exchange rates have been measured between 1,2-[2-13C]DPPC and the 13C-OH position of Y93 in the glycophorin transmembrane domain. These intermolecular distance measurements demonstrate that the relative orientation and location of membrane lipids and peptides can be established using RR NMR methods. PMID- 8193149 TI - Structure and orientation of the transmembrane domain of glycophorin A in lipid bilayers. AB - Rotational resonance (RR) NMR, circular dichroism (CD), and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy are used to establish the secondary structure and orientation of peptides corresponding to the transmembrane domain of human glycophorin A in dimyristoylphosphatidylcholine bilayers. An amide I vibrational frequency of 1650 cm-1 and negative CD absorption bands at 208 and 222 nm indicate that the peptide is largely alpha helical, while an order parameter of 0.35-0.50 in the ATR-FTIR measurements indicates that the peptide orientation is generally perpendicular to the bilayer plane. High-resolution structural data on the glycophorin A transmembrane (GPA TM) peptides were obtained by measuring the rate of magnetization exchange between pairs of specific 13C labels using RR NMR. The exchange rates are translated into internuclear distances with a resolution on the order of 0.3 A. These experiments are similar in design to previous experiments on crystalline peptides where the 13C labels were incorporated into amino acids separated by 2-3 residues in the peptide sequence but close together in space due to a helical peptide geometry [Peersen, O.B., Yoshimura, S., Hojo, H., Aimoto, S., & Smith, S.O. (1992) J. Am. Chem. Soc. 114, 4332-4335]. In the GPA-TM peptides, magnetization exchange rates measured between [1-13C]V80 and [2-13C] G83 between [1-13C]M81 and [2-13C]G83 in the middle of the transmembrane sequence correspond to internuclear distances of approximately 4.5 A and are consistent with a helical peptide structure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193150 TI - The adhesive specificity of the soluble human lectin, IgE-binding protein, toward lipid-linked oligosaccharides. Presence of the blood group A, B, B-like, and H monosaccharides confers a binding activity to tetrasaccharide (lacto-N-tetraose and lacto-N-neotetraose) backbones. AB - The immunoglobulin E-binding protein, epsilon BP (also known as CBP35, Mac-2, L 34, and L-29), is a beta-galactoside-binding protein of approximately 30 kDa and a member of the animal lectin family termed S-type or S-Lac. Multiple biological activities have been attributed to this lectin such as mediation of IgE binding to the surface of Langerhans cells and activation of mast cells through binding to the high affinity IgE receptor. In order to better understand the cell-binding activity and the proposed role for epsilon BP as a biological response modifier, we have studied the specificity of binding of the radioiodinated epsilon BP to a series of lipid-linked, structurally defined oligosaccharide sequences of the lacto/neolacto family. The results show that the minimum lipid-linked oligosaccharides that can support epsilon BP binding are pentasaccharides of the lacto/neolacto series and that the lectin binds more strongly to oligosaccharides of this family that bear the blood group A, B, or B-like determinants than to those bearing blood group H. This preferential binding of epsilon BP is also manifest with whole cells, as erythrocytes of blood groups A and B are more strongly bound by epsilon BP than those of blood group O. Blood group Le(a) and Le(x) sequences are not bound by the lectin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193151 TI - Detection of an intermediate in the folding of the (beta alpha)8-barrel N-(5' phosphoribosyl)anthranilate isomerase from Escherichia coli. AB - We have used thermodynamic and kinetic techniques to monitor the guanidinium chloride induced (GdmCl-induced) denaturation of N-(5' phosphoribosyl)anthranilate isomerase from Escherichia coli (ePRAI). Although CD monitored equilibrium denaturation curves are consistent with cooperative unfolding of the protein centered at 1.45 M GdmCl, fluorescence readings drop by over 25% in the region preceding the CD-monitored transition, suggesting non-two state behavior. Kinetics experiments measure a slow relaxation rate with negative fluorescence amplitude when protein is diluted from 0 to 0.5 M GdmCl, corroborating results from equilibrium conditions. Detection of several unfolding and refolding rates in final GdmCl concentrations from 0 to 5.0 M indicates the presence of at least one intermediate along unfolding and refolding pathways. GdmCl dependence of the relaxation rates can be explained most easily by a nonsequential mechanism for ePRAI unfolding, though a sequential mechanism cannot be ruled out. The data corroborate the fragment complementation studies of Eder and Kirschner [Eder, J., & Kischner, K. (1992) Biochemistry 31, 3617-3625], which are consistent with unfolding of the C-terminal portion of a yeast-derived PRAI in its folding intermediate. In ePRAI, such partial unfolding would expose W391 to quenching by solvent molecules; W356, ePRAI's other tryptophan, is buried in the hydrophobic core and is unlikely to be affected by local changes in structure. A C-terminally unfolded folding intermediate has been demonstrated in the folding of tryptophan synthase (alpha-subunit), a related beta alpha-barrel enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193152 TI - Thermodynamic properties of the transition state for the rate-limiting step in the folding of the alpha subunit of tryptophan synthase. AB - To gain insight into the physical properties of the transition state for the rate limiting step in the folding of the alpha subunit of tryptophan synthase from Escherichia coli, the urea dependence of the unfolding reaction was examined as a function of temperature. Consistent with a previous, more limited study [Hurle, M.R., Michelotti, G.A., Crisanti, M.M., & Matthews, C.R. (1987) Proteins 2, 54], the activation entropy for unfolding was found to be negative above 4 M urea. The present study extends this finding to show that both the activation entropy and enthalpy decrease with increasing urea concentrations between 4 and 7.5 M. The change in the heat capacity from the native to the transition state is positive and appears to increase with the denaturant concentration. The urea and temperature dependences of the unfolding rates were analyzed in terms of the denaturant-binding model of Tanford [Tanford, C. (1970) Adv. Protein Chem. 24, 1]. The values for the activation enthalpy and activation entropy of binding are in good agreement with those obtained from a calorimetric study of urea binding to unfolded proteins [Makhatadze, G.I., & Privalov, P.L. (1992) J. Mol. Biol. 226, 491]. These results show that (1) the binding of urea to the transition state of the alpha subunit has thermodynamic properties which are similar to those for urea binding to unfolded proteins, (2) the transition state is distinct from the unfolded conformation and exposes only a fraction of its urea-binding sites to solvent, and (3) the negative value for the activation entropy for unfolding reflects, in part, the ordering of urea on newly exposed surfaces.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193153 TI - Mechanisms of cellulases and xylanases: a detailed kinetic study of the exo-beta 1,4-glycanase from Cellulomonas fimi. AB - The exoglucanase/xylanase from Cellulomonas fimi (Cex) has been subjected to a detailed kinetic investigation with a range of aryl beta-D-glycoside substrates. This enzyme hydrolyzes its substrates with net retention of anomeric configuration, and thus it presumably follows a double-displacement mechanism. Values of kcat are found to be invariant with pH whereas kcat/Km is dependent upon two ionizations of pKa = 4.1 and 7.7. The substrate preference of the enzyme increases in the order glucosides < cellobiosides < xylobiosides, and kinetic studies with a range of aryl glucosides and cellobiosides have allowed construction of Broensted relationships for these substrate types. A strong dependence of both kcat (beta 1g = -1) and kcat/Km (beta 1g = -1) upon leaving group ability is observed for the glucosides, indicating that formation of the intermediate is rate-limiting. For the cellobiosides a biphasic, concave downward plot is seenj for kcat, indicating a change in rate-determining step across the series. Pre-steady-state kinetic experiments allowed construction of linear Broensted plots of log k2 and log (k2/Kd) for the cellobiosides of modest (beta 1g = -0.3) slope. These results are consistent with a double-displacement mechanism in which a glycosyl-enzyme intermediate is formed and hydrolyzed via oxocarbonium ion-like transition states. Secondary deuterium kinetic isotope effects and inactivation experiments provide further insight into transition state structures and, in concert with beta 1g values, reveal that the presence of the distal sugar moiety in cellobiosides results in a less highly charged transition state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193154 TI - Structure and expression of mRNA for vitellogenin in Bombyx mori. AB - Vitellogenin, a precursor of major yolk protein of the silkworm, Bombyx mori is a tetramer composed of each two molecules of heavy and light subunits. We cloned mRNA sequence for the B. mori vitellogenin and analyzed its structure. Sequence alignment of several overlapping cDNA clones indicated that the vitellogenin mRNA is approx. 5.7 kb, containing an open reading frame for a peptide with 1782 amino acid residues. By comparing the deduced amino acid sequence with the amino terminal primary structures of vitellogenin subunits, it is suggested that the heavy and light subunits of the B. mori vitellogenin are encoded by a single contiguous mRNA. The primary translation product of the vitellogenin mRNA was detected in the microsomal fraction prepared from the fat body of vitellogenic females. Northern blot analysis of the fat body RNA demonstrated that the biosynthesis of vitellogenin in B. mori is regulated in a tissue-, sex- and stage specific manner at the level of mRNA. Possible cause for discrepancy between the present results and our previous proposal (Izumi, S. and Tomino, S. (1983) Insect Biochem. 13, 81-85) on the biosynthesis of B. mori vitellogenin is also discussed. PMID- 8193155 TI - Characterization of canine pancreas kallikrein cDNA. AB - Using a combination of primer extension and RT-PCR, the cDNA encoding a canine tissue kallikrein expressed in the pancreas was cloned and sequenced. The cloned 0.85 kbp cDNA contained a complete open reading frame encoding a polypeptide of 261 amino acids. The calculated molecular mass of the processed, unglycosylated, 237 amino acid protein was 26,428 Da. Its mRNA was expressed at high levels in the pancreas, kidney and submaxillary gland. The sequence of the encoded protein was highly homologous with canine prostatic arginine esterase (66%) and human renal/pancreatic kallikrein (74%). Therefore, the cloned cDNA encoded a previously uncharacterized canine kallikrein enzyme which was named dog renal/pancreatic kallikrein or dK2 according to the new nomenclature for kallikrein gene family members. Because of its specific pattern of tissue expression and the presence of all the amino acid residues necessary for kininogenase activity, we suggest that dK2 is the canine true tissue kallikrein. PMID- 8193156 TI - Sequence analysis of the agaB gene encoding a new beta-agarase from Vibrio sp. strain JT0107. AB - An agarase gene (agaB) was cloned from genomic DNA of Vibrio sp. strain JT0107. Analysis of the 3200 nucleotide sequence just before the agarase 0107 gene (agaA) which existed in genomic DNA of Vibrio sp. strain JT0107 revealed a putative single open reading frame coding for 955 amino acids. Comparison of the deduced amino acid sequence of AgaB to that of agarase 0107 revealed the existence of partially highly homologous regions. A part of this gene was expressed in Escherichia coli to yield a protein with agarase activity. This is the first report of evidence by genetic analysis that at least two different kinds of agarases exist in strain JT0107. PMID- 8193157 TI - An Acanthamoeba ubiquitin-fusion protein; cDNA and deduced protein sequence. AB - We have isolated and sequenced a 525 bp ubiquitin cDNA (Acantub1) from the soil amoeba Acanthamoeba castellanii. The deduced amino acid (aa) sequence reveals that the Acantub1 gene product is a fusion protein consisting of 128 aa (76 aa ubiquitin and 52 aa 60S ribosomal protein). The Acantub1 protein sequence has unique substitutions at aa 28 (glutamine for alanine) and 121 (tryptophan for leucine) compared to the 8 highest homologous sequences in the databank. A putative 'zinc finger' nucleic acid-binding domain was located in the 52 aa ribosomal protein. Northern analyses reveal that the Acantub1 gene is regulated during development. PMID- 8193158 TI - Pseudomonas aeruginosa PA-I lectin gene molecular analysis and expression in Escherichia coli. AB - This communication describes a Pseudomonas aeruginosa DNA fragment (cloned in lambda gt11) which contains the structural gene coding for the galactophilic PA-I lectin (pa-1L, 369 bp) and an additional downstream 237 bp sequence. This DNA is relatively rich in G + C (54%), and exhibits a strong codon preference biased for XXC and also for XXG. The Shine-Dalgarno site of the gene is preceded by an adjacent ATATAT sequence resembling the -10 sequence of the Escherichia coli promoter. The stop codons are followed by a stem and loop structure--typical of the rho-independent transcriptional stop element. This lambda gt11-cloned DNA was expressed in E. coli Y1090 cells. The resulting cell lysates exhibited a galactose-specific hemagglutination and a protein with electrophoretic mobility similar to that of the native PA-I, which were both absent from E. coli lysates infected with ovalbumin gene-bearing bacteriophages. The recombinant PA-I, purified by gel filtration and affinity chromatography, was shown to be a galactophilic hemagglutinin resembling the native lectin in molecular weight and selective reactivity with rabbit anti native PA-I serum. These results are important for development of a safe Pseudomonas aeruginosa vaccine using recombinant DNA techniques, thus avoiding contamination with toxic products of this bacterium. PMID- 8193159 TI - Cloning of a family of cyclins from Arabidopsis thaliana. AB - Degenerate oligonucleotide primers corresponding to two conserved regions in animal cyclins were used to amplify cyclin sequences from Arabidopsis thaliana by polymerase chain reaction (PCR). Screening of a floral meristem cDNA library with two distinct PCR-generated cyclin sequences resulted in the isolation of four different cyclin cDNAs. Southern analysis of genomic DNA and sequence information from the isolated clones suggest that there is a family of cyclins in Arabidopsis. PMID- 8193161 TI - Conserved regulatory elements in the type I DNA topoisomerase gene promoters of mouse and man. AB - The gene for mammalian type I DNA topoisomerase is constitutively expressed, but also regulated by a number of external stimuli. We compared the nucleotide sequences of the human and the mouse topoisomerase I gene promoters because promoter elements, essential for basic as well as regulated gene expression, should be conserved during evolution. We found that proximal upstream sequences are highly conserved and include potential binding sites for ubiquitous transcription factors, a regulatory CRE site as well as two novel promoter elements that have been shown to be important for the expression of the human gene. The more distal parts of the upstream sequences are less well conserved but include two regions that are almost identical in the human and the mouse gene. One of these regions contains a binding site for a basic-helix-loop-helix/leucine zipper protein, and the other contains an AT-rich element with the potential for DNA bending. PMID- 8193160 TI - Expression and myristoylation of NAP-22 using a baculovirus transfer vector system. AB - NAP-22 is a brain enriched acidic protein localized in the membrane fraction. The peptide sequence of NAP-22 elucidated from the cDNA sequencing, however, showed that NAP-22 is a very hydrophilic protein having no transmembrane regions. The peptide sequence analysis also showed that NAP-22 has a consensus sequence of N myristoylation and the presence of polybasic domain in its N-terminal region. These sites could be the anchoring sites to localize to the membrane. In this study, we showed the myristoylation of NAP-22 using a Baculovirus expression system and also showed a liposome binding ability of the expressed protein in Escherichia coli. PMID- 8193162 TI - On the binding of isolated yeast tRNA(Phe) anticodon arm to Escherichia coli 30S and 70S ribosomes. Guanosine-42 is important for the binding. AB - Conditions for the reversible binding of isolated anticodon arm of yeast tRNA(Phe) (15-nucleotide, corresponding to nucleotides N28-N42) to the P site of Escherichia coli 30S and 70S ribosomes have been determined. The affinity constant for the anticodon arm binding to 70S ribosomes is shown to be only 30 fold weaker than that for the binding of total tRNA(Phe). The affinities of yeast tRNA(Phe) and the anticodon arm for 30S subunits and of the anticodon arm for the total 70S ribosomes are shown to be equal. These data imply that the anticodon arm moiety of tRNA(Phe) mainly contributes to the tRNA-70S ribosome interaction, i.e., it contributes for the most part to the total free energy of the deacylated tRNA(Phe) interaction with the P site of the 70S ribosome. By taking into account additional contacts in the 3'-CCA end, other contacts in the region besides the anticodon arm and 3'-CCA end are presumably absent. Within the anticodon arm removal of the 3'-end nucleotide corresponding to guanosine-42 in tRNA(Phe) decreases the association constant of the anticodon arm-ribosome interaction 15 fold. Replacement of this guanosine with other nucleosides as well as modification of the ribose moiety (oxidation and reduction) does not affect the affinity. The replacement data are very likely to indicate that G42 affects the anticodon arm affinity by forming a direct contact with ribosome. PMID- 8193163 TI - Antisuppression by a mutation in rpsM(S13) giving a shortened ribosomal protein S13. AB - The phenotype associated with an rpsM(S13) mutation, originally isolated in Escherichia coli in a selection for pseudoreversion of streptomycin dependence, was studied in strains lacking the original mutations for antibiotic dependence. The rpsM mutation gives a decreased translational step time and a reduced growth rate. It functions as a strong antisuppressor to both the serU(Su1) amber suppressor and the trpT(Su9) opal suppressor, whereas the tyrT(Su3) amber suppressor is much less affected. The small ribosomal subunit from the rpsM mutant shows a reduced sedimentation coefficient but is able to form apparently normal 70S ribosomes as judged by ultracentrifugational analysis. Cloning and sequencing show that the rpsM mutation is a CAG to TAG alteration at codon position 100, giving an S13 protein which is shortened by 19 amino acids at its C terminal end. This implies that the C-terminal domain of the protein that is involved in binding to 16S ribosomal RNA should be affected. PMID- 8193164 TI - Induction of aromatase gene expression in human placental choriocarcinoma (JAR) cells by phorbol esters. AB - The expression of aromatase in JAR cells, human placental choriocarcinoma cells, was found to be induced by the treatment of phorbol 12,13-diacetate (PDA), phorbol 12,13-didecanoate (PDD), or phorbol 12-myristate 13-acetate (TPA), but not 4 alpha-phorbol, 12,13-didecanoate (4 alpha PDD). At 1 microM or higher concentrations, these phorbol esters increased the level of aromatase mRNA and aromatase activity in a dose- and time-dependent fashion. Since the rates of the decrease of aromatase mRNA in phorbol ester treated and untreated cells were not significantly different in the presence of actinomycin D, the induction was not due to an increase in the stability of aromatase mRNA, but rather due to an increase in the synthesis of aromatase mRNA. The stimulation was not inhibited by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). It is thought that the induction either follows a protein kinase C-independent manner or results from a down-regulation of protein kinase C pathway. Studies from several laboratories have revealed that the regulation of the expression of aromatase in estrogen producing cells involves very complex processes. The apparent induction of aromatase expression in JAR cells by phorbol esters represent a mechanism modulating estrogen production in human placental choriocarcinoma cells, that may or may not be utilized in other estrogen-producing cells. PMID- 8193165 TI - The exon 4 poly(A) site of the human calcitonin/CGRP-I pre-mRNA is a weak site in vitro. AB - The human calcitonin/CGRP-I (CALC-I) pre-mRNA is processed in a tissue-specific alternative way into either calcitonin (CT) or calcitonin gene-related peptide-I (CGRP-I) mRNA. The exons 1 to 3 are common exons. They are spliced to exon 4, which becomes polyadenylated to form CT mRNA, or to exon 5 and the polyadenylated exon 6 to form CGRP-I mRNA. Polyadenylation at exon 4 and splicing of exon 3 to exon 5 are mutually exclusive processing reactions. Only splicing of exon 3 to exon 5 was detected in vitro, with a minigene containing the exon 3 to exon 5 region. No polyadenylation at the exon 4 poly(A) site could be observed. Investigation of the properties of the exon 4 poly(A) site in vitro shows that it is inefficiently used in vitro. Cleavage and polyadenylation of short RNAs containing only the exon 4 poly(A) site is strongly dependent on the 3' length of the RNA. Downstream sequences located within 39 nucleotides from the cleavage site are required for optimal cleavage and polyadenylation. When the exon 4 poly(A) site in the minigene is replaced with the strong adenovirus L3 or rabbit beta-globin poly(A) sites, these sites can be efficiently used in vitro. PMID- 8193166 TI - Structure and developmental expression of a larval cuticle protein gene of the silkworm, Bombyx mori. AB - Structure and expression of the gene for a larval cuticle protein of the silkworm, Bombyx mori were studied. A major cuticle protein, termed 'LCP30' was purified from the urea extract of integuments of the fifth (final) instar larvae. Immunoblot analysis by use of the anti-LCP30 antibody revealed that LCP30 begins to accumulate in larvae as early as 10 h after hatch and is present throughout the larval stages. The LCP30 epitope is also detectable in the adult abdominal integument but is absent from pupal integument and adult wing. Screening of an epidermal cDNA expression library with the antibody probe yielded a cDNA clone for LCP30. Primary structure deduced from the cDNA sequence showed that LCP30 bears an arginine-glycine-aspartate (RGD) sequence. The region around this domain exhibits striking similarity with the amino acid sequences found in vertebrate collagens. The genomic DNA clone coding for LCP30 was isolated by screening a B. mori gene library with the LCP30 cDNA probe. The gene consists of five exons interspersed by four introns spanning over 2.7 kb region of chromosomal DNA. The LCP30 mRNA is detectable at high levels at larval intermolt stages, gradually declines after the fourth molt and totally disappears at mid-fifth larval instar, indicating that the expression of LCP30 gene is regulated in a stage-specific fashion in the epidermal cells. Topical application of a juvenile hormone analogue (methoprene) to the fifth instar larvae followed by RNA blot and S1 nuclease mapping analyses of the epidermal RNA proved that juvenile hormone activates transcription of the LCP30 gene. PMID- 8193167 TI - Analysis of the 22 kbp long psbD-psbC gene cluster of Euglena gracilis chloroplast DNA: evidence for overlapping transcription units undergoing differential processing. AB - The clustered genes psbD and psbC covering together close to 22,000 nucleotides contain ten and eleven exons, respectively. The corresponding translation products, i.e, Photosystem II core 34 kDa (D2) protein and the CP43 chlorophyll binding protein are highly conserved. Introns vary in length from 305 to 4144 nucleotides. The two genes have about 900 nucleotides in common including an intron. To obtain stable mRNAs of about 1400 (psbD) and 1500 (psbC) nucleotides the pre-transcripts must undergo differential processing and/or splicing events within the overlapping region. PMID- 8193168 TI - Characterization of a chicken cDNA encoding the retinoblastoma gene product. AB - We have isolated a chicken cDNA that encodes the retinoblastoma susceptibility gene product (RB). The predicted amino acid sequence of the chicken RB protein is highly similar to that of the mouse, human and Xenopus RB proteins in regions of known functions; however, chicken RB has distinct species-specific differences, including a shorter N-terminal region as compared to the mouse and human RB proteins. In vitro-translated chicken RB co-migrates on SDS-polyacrylamide gels with endogenous RB synthesized in transformed chicken spleen cells. Finally, chicken RB is located in the nucleus of chicken embryo fibroblasts when overexpressed from a retroviral vector. PMID- 8193169 TI - Sequence of the sheep fetal beta globin gene and flanking region. AB - The sheep beta F globin gene has been sequenced completely, including 829 bases of 5' flanking region and 1368 bases 3' to the stop codon. In evolutionary terms, this gene is a homolog of the adult beta-like globin genes, including human beta. Over the course of evolution of Bovidae (comprised of sheep, goats, and cattle) the expression of beta F has become restricted to the fetal compartment of development. Comparisons between beta F and other closely related Bovidae beta globin genes indicate repetitive sequences that were inserted in these genes over the course of their divergence and a region which may be functionally significant to the developmentally regulated expression of beta F. PMID- 8193170 TI - The genomic organization of the rat angiotensin II receptor AT1B. AB - Expression of two subtypes of angiotensin type 1 receptor (AT1A and AT1B) seems to be controlled by different mechanisms. As a step toward the elucidation of difference in the mechanism in their gene expression, the genomic organization of rat angiotensin II type 1B receptor was investigated. Rat genomic DNA fragments were cloned by screening a genomic library with fragments from two cDNA clones (2.3 and 2.2 kb) encoding the rat AT1B receptor. Three lambda clones were isolated, and the hybridizing restriction fragments were sequenced. Comparison of the genomic clone DNA and cDNA sequences revealed that the rat AT1B receptor gene contains three exons and two introns. Two of the exons encoded 5' untranslated sequences while the third exon contained the entire coding region. The 5' flanking region contained the typical sequence motifs found in many eukaryotic promoters including a TATA box and a potential SP1 binding site. The transcription initiation site was located at -8 bp upstream the 5' end of the cDNA in the 5'-flanking region. PMID- 8193171 TI - TUBIS, a fossilized retroposon in the tubulin gene cluster of Trypanosoma brucei. AB - The genome of Trypanosoma brucei contains many copies of TRS/ingi, a retroposon like element of about 5 kb length. One vestigial member of this family, TUBIS, is found in the tubulin gene cluster. The element has sequence homologies to reverse transcriptase. The similarity to TRS/ingi is lost after 4 kb, resulting in a 3' truncated element. The sequence following downstream shows similarities to 5' flanking regions of VSG genes. PMID- 8193172 TI - Social isolation modifies the response of mice to experimental Mengo virus infection. AB - To investigate the effects of social isolation on host resistance male mice were housed either individually (IH) or in groups of four or five (GH). All animals were infected with MengoM,L virus. Incubation time (INCUB), duration of illness (ILL), death rate (DR), histopathological changes, and serum corticosterone levels (CORT) were recorded. First, the effect of IH starting 4 days prior to infection was studied in 5 different inbred strains. Next, the effect of different IH length was examined, and the role of T-cells was investigated by comparing euthymic (+/+) and athymic (nu/nu) NMRI mice. Finally, the effects of the infection on CORT in IH and GH mice were compared in C57BL/6 mice. The major findings were: 1. IH significantly increased ILL in all but the DBA/2 strain, whereas DR was not affected except in C57BL/6. 2. Longer IH (starting 35 [DBA/2] or 10 [NMRI] days prior to virus inoculation) significantly shortened INCUB and prolonged ILL, but IH starting on the day of virus inoculation [DBA/2] significantly prolonged INCUB and shortened ILL. 3. NMRI nude mice exhibited an unaltered DR accompanied by a tremendously prolonged INCUB. 4. Investigations in C57BL/6 mice revealed a significant rise of CORT after infection. This increase was higher in IH compared to GH mice. It is suggested that IH attenuates T-cell mediated inflammatory processes and/or increases macrophage activation, which in turn results in a prolonged course of the disease. PMID- 8193173 TI - IgG subclasses of the multimammate rat, Mastomys coucha: isolation and characterization of IgG1 and IgG2. AB - The objective of the study was to characterize the IgG-system of Mastomys coucha and to provide antibodies specific for IgG subclasses of this animal species. Serum proteins binding to protein A at pH 8.0 could be eluted in two distinct peaks at pH 7.5 - 6.2 and pH 5.0 - 3.9. The fractions were analysed by SDS-PAGE and immunoelectrophoresis. Both tests suggested an IgG character of the fractions. Based on their migration behavior in the electric field they were classified as IgG1 (anodic position) and IgG2 (cathodic position). After cleavage of IgG1 and IgG2 with papain, the Fc fragments were isolated by their binding to protein A and used to raise antisera in rabbits. The specificity of these antisera to IgG1 and IgG2 was improved by mutual affinity purification. Subsequently these specific reagents were used for further characterization of IgG1 and IgG2. Thus, affinity chromatography of IgG to protein G allowed a differentiation of IgG1 into two subtypes which either bound to protein G at pH 8.0 or not. In combination with isoelectric focussing and 2-dimensional immunoelectrophoresis the results suggest the occurrence of two and three subtypes of IgG1 (IgG 1a-b) and IgG2 (IgG 2a-c) respectively. A synoptical table of available information on the immunoglobulins of M. coucha including IgM, IgA, IgE and a homocytotropic IgG3 is presented. In addition, serum levels of IgG1 and IgG2 are determined in male and female M. coucha of different ages. PMID- 8193174 TI - Alveolar epithelial cells in experimental lung emphysema. Analysis of methods for type II pneumocyte identification among cells isolated from the respiratory tract of rats. AB - Total and differential counts of cells isolated from the lungs of Wistar rats with experimental emphysema were performed. Emphysema was induced by a single intratracheal dose of papain solution (20 mg/kg b.w.). Rats were sacrificed 1, 7, 14 and 28 days later. Cells were isolated from the lungs through multiple bronchoalveolar lavage. An attempt to identify type II pneumocytes was undertaken. Our observations suggest that none of the methods applied for identification of type II pneumocytes are completely specific. At the same time they stain type II cells and subpopulations of alveolar macrophages heavily loaded with phagocytized surfactant elements. However those methods are simple and enable an approximate evaluation of damage and regeneration processes in the extracellular alveolar lining layer and epithelium. PMID- 8193175 TI - Measurement of the dynamics of the cerebrospinal fluid system in the rat. AB - A technique for intracranial pressure (ICP) monitoring in the rat that enables the measurement of the cerebrospinal outflow resistance (RCSF) and the intracranial pressure-volume index (PVI) is described. A permanent catheter placed into the cisterna magna through the occipital bone was used. ICP, RCF and PVI were measured in ten LEW rats. The baseline ICP was 8 +/- 1.7 mm Hg (Mean +/- S.D.). The PVI was 0.0518 +/- 0.018 ml. The RCSF was 464 +/- 196 mm Hg ml-1 min-1 which is less than reported previously. The cannulation technique easy and gives reliable pressure tracings. It enables ICP monitoring and estimation of the dynamics of the cerebrospinal fluid (CSF) system during experimental surgical procedures in the rat. PMID- 8193176 TI - An improved technique for visually controlled pinealectomy in the rat. AB - An improved method for pinealectomizing rats and other small laboratory rodents is described which avoids bleeding and allows excision of the organ under exact visual control. After removing a small piece of the skull dorsal to the confluence of the transverse and dorsal sagittal sinuses, the latter is ligated and cut. The underlying pineal gland is then exposed and may be excised reliably without damage to the gland tissue or to adjacent brain structures. Intra- and post-operative complications are extremely rare. PMID- 8193177 TI - The viscoelasticity of blood and plasma in pig, horse, dog, ox, and sheep. AB - There is little data on blood viscosity in different animals. Therefore a comparison was performed between five species by an in-vitro method using oscillatory flow. At shear rates from 1 to 150/sec the viscous and the elastic component of the complex blood viscosity was highest in pig, followed by horse, dog, ox, and sheep. Plasma viscosity and plasma density were similar in dog and sheep and were higher in ox. The differences in whole blood viscosity were obviously related to the variable interspecies hematocrit, and may also be influenced by different aggregation tendencies. Aggregation in ox was low despite a high plasma fibrinogen. It seems that erythrocytes in sheep and ox remain separately suspended in a relative dense plasma. This may indicate that formation of microthrombi is less likely to occur in ox and sheep than in pig, horse, and dog. PMID- 8193178 TI - Message from the president: voices: the critical difference. PMID- 8193179 TI - "Yes, Virginia; there is a knack to solving problems". PMID- 8193180 TI - A new approach to assessment and documentation of conscious sedation during endoscopic examinations. AB - Assessment and documentation of patient responses to treatment and/or invasive procedures are important facets of nursing care. The purpose of this article is to describe a tool for assessing and quantifying a patient's response to sedation and tolerance of a specific diagnostic and/or therapeutic procedure. Use of the conscious sedation scale will allow the nurse to objectively measure the patient's outcome. This tool will also facilitate better patient care and documentation and substantiate nursing intervention. PMID- 8193181 TI - Mechanical lithotripsy. AB - Endoscopic lithotripsy is a procedure used for the removal of large stones in the common bile duct that cannot be removed after sphincterotomy. This procedure causes fragmentation of large stones, which allows easier retrieval of stones by other instruments such as balloons or baskets. There are currently two types of mechanical lithotripsy: one type uses an instrument called a mechanical lithotriptor, and the second type uses an electrohydraulic lithotriptor. This article focuses on mechanical lithotripsy. Since it is vital for the operator of this equipment to understand its function, assembly, disassembly, and maintenance, specific guidelines are provided. PMID- 8193182 TI - Using available resources to implement research. AB - Nurses practicing in hospital settings are in a unique position to become involved in research. Day-to-day contact with a variety of patients offers the ideal opportunity to launch an investigation based on actual or potential nursing problems. Often these nurses are not aware of the resources that could help them implement a study that would provide valuable data to staff and others who work with a similar patient population. The purpose of this article is to aid staff nurses in initiating research by discussing resources that may be available within their immediate geographical area. PMID- 8193183 TI - Developing an abstract and plan for presenting at education programs. AB - Presenters at the Society of Gastroenterology Nurses and Associates education programs are now being asked to submit abstracts on the proposed topic for presentation. In this article the author discusses the steps in planning and developing a presentation as well as submitting an abstract for consideration. PMID- 8193184 TI - GI nursing: the community health aspect. AB - Much of the research and literature regarding gastrointestinal nursing addresses concerns of clients in the hospital or outpatient setting. This article focuses on a larger clientele, the well elderly aggregate in the community. Implementation of the nursing process with participants of a local senior center indicated the need for a gastrointestinal education program. A GI health program with a long-range goal of reducing the number of deaths caused by colon cancer was developed and presented. The goal of the program was to educate individuals about colon cancer and the importance of early detection. In this article, the authors describe the application of the nursing process with a well elderly population and the results of that experience for the client and for the GI nurse in the community. PMID- 8193185 TI - Staffing levels in endoscopy units. AB - Staffing the endoscopy area has become increasingly complex. Growth in procedure volumes, changes in technology, and the application of endoscopy in the diagnosis and treatment of disease contribute to the complexities. The manager must deal with these changes, maintain costs, and still provide adequate staffing to ensure patient safety and quality care. The purpose of this article is to present the results of a laboratory manager survey conducted in 1990. Of 51 laboratory managers who responded, those who rated their laboratories to be adequately staffed averaged 4.2 hr per procedure. The survey results may be useful to laboratory managers seeking to calculate staff needs in a typical endoscopy area. PMID- 8193186 TI - A solution to the endoscopic removal of difficult bile duct stones. PMID- 8193187 TI - Video endoscopic fluoroscopy: a computer process comes of age. PMID- 8193188 TI - Propulsid (cisapride). AB - Propulsid is indicated in the treatment of patients with nocturnal heartburn due to gastroesophageal reflux disease. Propulsid administration increases lower esophageal sphincter pressure and increases esophageal acid clearance. PMID- 8193190 TI - [Use of time-of-flight mass spectrometry with ionization division fragments of californium-252 for studying the mechanisms of action of drugs on DNA and its components]. AB - Using soft-ionization mass spectrometry (252-Cf particle desorption mass spectrometry, PDMS) a minor adduct of anticancer drug prospidine and deoxyguanosine-5-phosphate (pdG) has been found. It has been shown experimentally that PDMS is very useful for study of biological mixtures as well as mechanisms of interactions between drugs and biomolecules. PMID- 8193189 TI - [The mechanism of metabolic denitration of nitroheterocyclic compounds]. AB - It has been found that denitration of nitroheterocyclic drugs (NHCC) in mouse liver homogenate is one of the pathways of their biotransformation. This process is accompanied by the release of NO and NO-heme iron complex formation. The yield of complex increases linearly with time of NHCC incubation with liver homogenate and depends on NHCC structure. The ESR spectrum of the complex represents a superposition of spectra of NO with hemoglobin and NO with the other heme containing proteins. NHCC denitration is inhibited by metyrapone, which is an evidence of cytochrome P-450 involvement in their metabolic denitration. PMID- 8193191 TI - [Reaction of fluorescamine with nitrogen bases in nucleotides and single-stranded synthetic and native oligonucleotides]. AB - Reactions of fluorescamine with nucleoside bases have been studied. Fluorescamine reacts with NH2 groups of dA, dG, dC, and the characteristic pyrrolinone spectrum with maximum at 490 nm appears. Fluorescamine does not react with dU and dT. The reaction is pH-dependent, but not linked to protonization of amino groups. pK values for dA, dG, dC are respectively 7.3, 8.4, 8.7. At pH greater than 10 or lower than 3 the fluorescence decreases due to formation of non-fluorescent fluorescamine derivates. The average fluorescence yield of pyrrolinone (the product of reaction of fluorescamine with denatured DNA and single-stranded polymers containing dA) is 2.7-3.5 fold higher as compared to mixture of individual nucleotides. The studied reaction can be used sequencing of nucleic acids. PMID- 8193192 TI - [Modeling the dynamics of polyunsaturated lipids in biological membranes]. AB - Molecular dynamics simulations were performed for the docosahexaene C22H34 and docosan C22H46 chains, which are typical components of phospholipids in biological membranes. The calculations were carried on at two temperatures of 276 K and 320 K. The time of each computation covered 600 ps. The torsion angles variations phi i(t), i = 1, 2, ..., 21 has been analysed. It has been demonstrated that in docosan phi i(t) are oscillating with the amplitudes of 10 15 degrees, which are slightly increasing with the temperature. The average torsion angle positions correspond to the rotation-isomeric model. In docosahexaene chain the amplitudes of the torsion angles oscillations around a simple bond, connected to a double one, are about twice greater and their frequencies are about 3.5 times less then the docosan have. It has been noted that these angles also possess states, living up to 5 ps, which do not correspond to the regions of the minimum potential energy of molecular fragments. Average frequency of conformational transitions in docosahexaene chain is about six times greater than in the docosan one. PMID- 8193193 TI - [The effect of cholesterol and dicetylphosphate on the physical parameters of liposomes]. AB - The physical parameters of liposomes from phosphatidylcholine with cholesterol or dicetylphosphate were investigated. The sizes, electrophoretic mobility, surface density charges of these liposomes were estimated. It has been shown that dicetylphosphate, as well as cholesterol increases the thickness of bilayer of the lecithin liposomes and at the same time the area occupied by one lipid molecule has not been changed by dicetylphosphate in contrast to cholesterol. PMID- 8193194 TI - [Structural ordering model biomembrane]. PMID- 8193195 TI - [Thermodynamic effectiveness of active transport of calcium ions]. AB - Computation of variation of general and partial free energy, exemplified by intracellular transport of calcium ions performed by sarcoplasmic reticulum Ca(2+)-ATPase, is used to demonstrate that the system of active transport of calcium ions works effectively even if transmembrane difference of electric potentials is absent. The possibility that local redistribution of charges on molecules complexes influences the Ca2+ transfer, is discussed. PMID- 8193196 TI - [Effectiveness of energy transformation during active transport of ions in a biomembrane]. AB - A statistical model of active ion transport in biomembrane is presented. The coefficient of energy conversion for linear and nonlinear processes in this system is obtained. It is shown that in the linear case this coefficient equals to the one obtained in linear thermodynamics. Based on the maximum of this coefficient, the transport parameters for ions are found. The results of the statistical model are in good agreement with experiments on biological membranes. PMID- 8193197 TI - [The effect of weak electric action on the triggering system of transmembrane ionic transfer]. PMID- 8193198 TI - [Vesiculation of erythrocytes during storage and connection of it with other processes in the cell]. AB - The activation energies of three processes (AT-depended vesiculation, release of potassium ions from erythrocytes and formation of methemoglobin) in erythrocytes incubated in phosphate buffer are measured in the range 4-37 degrees C. It is show that the Arrhenius plots for the first two processes have the same characteristics namely break at temperature around 18 degrees C, and Ea-58 kJ/mol at t > 18 degrees C. These data suggest that the velocity of ATP-depended vesiculation of erythrocytes is determined by the membrane permeability to monovalent cations. The appearance of methemoglobin in extracellular medium is characterized by a distinct value Ea(120 kJ/mol), although kinetics of this process is similar to vesiculation kinetics. Connection between considered processes and interrelation between ATP-depended vesiculation and spontaneous vesiculation are discussed. PMID- 8193199 TI - [Acidic hemolysis of erythrocytes depending on the temperature and storage time]. AB - Acidic resistance of erythrocytes, measured at temperatures of 5, 10, 15, 20, 24, 28, 31, 35, 40 degrees C, varies in course of 25-day hypodermic blood storage. Dynamics of the resistance change depends on the temperature. PMID- 8193200 TI - [The calcium pump in the sarcolemma controls smooth muscle relaxation]. AB - In order to identify the functional role of the sarcolemma calcium pump in the control over smooth muscle relaxation there was studied the effect of temperature on relaxation kinetics of myometrium carbachol contracture, actomyosin superprecipitation isolated from this object and Mg2+, ATP-dependent transport of Ca2+ in the fraction of uterus sarcolemma vesicles. The activation energies of the processes under study were determined in comparison. It was concluded from the evidence obtained that relaxation of the smooth muscle contracture is controlled by the stimulated temperature increase and by Na(+)-independent trans sarcolemma release of Ca2+ from the myocytes sensitive to La3+ effect. The release is provided by the calcium pump of the plasmic membrane. PMID- 8193201 TI - [A functional model of the electrical potential of skin]. AB - A model of the skin electrical potential has been developed. It contains electrical and functional parameters of the sweating and their dependence on efferent innervation. The analytical expression of the skin electrical potential which explains basic experimental results has been constructed. PMID- 8193202 TI - [Study of excited membrane refractory period length in patients using biological feedback to an interference current device]. AB - The authors generalized the experience of interference current apparatus application for the treatment of acute disease and trauma in the N.V. Sklifosovsky Scientific and Research Institute for Emergency Medicine (Moscow). A kind of recorder for reading the interfinger electric resistance of patient skin was offered as a biologic feedback to this apparatus aimed at individualized treatment. The values of the "resonance" frequencies shown by the recorder of the biological feedback to the interference current apparatus allow to determine the duration of the refractivity of excitable membranes in patients in the process of the complex treatment. PMID- 8193203 TI - [Reverse correlation between natural resistance of mice to transplanted leukemia EL-4 and rectal temperature]. AB - Mice F1 (CBA x C57Bl) life span after transplantation of standard number of leukemia EL-4 cells at different clock hours was evaluated. At the same time, as injection was done, rectal temperature of mouse was measured. Both parameters showed circadian trend. Mice life span was in negative correlation with rectal temperature. So it is possible to consider temperature rhythm as marker rhythm of natural antitumor resistance. PMID- 8193204 TI - [Modeling pattern recognition in real neuronal structures]. AB - A neural net model imitating the pattern recognition in nature is constructed. The model is based on the synergistic principles of pattern competition in course of the recognition process, where only the pattern nearest to the offered one survives. The proposed neural net uses a only small amount of information as compared with existing algorithms. For modelling of the natural pattern cognition a method of brightness segmentation has been used, which allows one to transform the initial picture to a less clear one. The information properties of the proposed algorithm are analysed. PMID- 8193205 TI - [Daily changes in the carbon isotope composition of CO2 in expired air of persons with various metabolic disorders]. AB - Daily variations of the aspiration CO2 carbon isotope content (CIC) were studied at three metabolic states: norm, insulin-dependent diabetes (IDD), and obesity. The groups of subjects were studied in a clinic during 24 hours. Analysis of the delta 13C daily curves of the exhaled air CO2 allowed us to find the link between variations of CIC with daily rhythms in the organism and with metabolic shifts at IDD and obesity. At metabolic norm it is possible two phases on the daily curve, corresponding to daytime and nighttime metabolism types with hormonally regulated transition between them. The daytime phase of the curve consists of altering maxima and minima, linked to periodicity in feeding and movement activity. The nighttime phase is characterized by continuous enrichment of CO2 by 12C. At IDD in insulin therapy conditions the most prominent difference from norm and obesity is the stable CIC at nighttime. At daytime during weakening of the exogenous insulin action there appear horizontal regions on the delta 13C CO2 curves, similar to the nighttime behaviour. At obesity the daily curves are close to the normal ones, but they are more smooth and impoverished in 13C. No clear transition between the daytime and nighttime metabolism types can be observed. At obesity and IDD the character of the daily curves can be observed. PMID- 8193207 TI - Interference pattern in perineal muscles. A quantitative electromyographic study in patients with faecal incontinence. AB - The aim of this study was to investigate the possibility of neuromuscular dysfunction in patients with faecal incontinence by measuring interference patterns in the external anal sphincter and puborectalis muscles with quantitative electromyography. The design was an open study including 20 patients with faecal incontinence; in 14 the aetiology was idiopathic and 6 had rupture of the external anal sphincter. Electromyographic interference patterns (turns/amplitude analysis) measured at rest and during maximum voluntary contraction in all patients were recorded together with fibre density measured by single fibre electromyography (n = 10) and anal pressure measured at rest and at maximum contraction (n = 17). A comparison was made with results of a previously published series of reference values taken from normal volunteers. The density of the interference pattern on maximum contraction of the puborectalis muscle was significantly lower among the patients with idiopathic faecal incontinence than among the reference group (137 compared with 241 turns/second, p < 0.01). There was also a significant difference on maximum contraction of the anal sphincter muscle among the group in whom it was ruptured compared with the reference group (76 compared with 165 turns/second, p < 0.05). Fibre density increased with age and was significantly higher among those with idiopathic incontinence (1.64 (0.2) compared with 1.33 (0.1) in the reference group, p < 0.01). There were no significant differences in anal manometry measurements between the groups. In conclusion, in patients with faecal incontinence the role of central activation of the perineal muscles is important, though other factors may play a part. PMID- 8193206 TI - Intraarterial infusion of autologous lymphocytes for the treatment of refractory lymphoedema. Preliminary report. AB - OBJECTIVE: To evaluate the results of the treatment of lymphoedema by intra arterial infusion of autologous lymphocytes. DESIGN: Open study. SETTING: University Hospital. SUBJECTS: 13 patients with refractory lymphoedema. INTERVENTIONS: Lymphocytes were separated from the patient's own blood using a blood cell separator; about 100 cc of lymphocyte dominant blood separated from this blood was immediately infused into the proximal artery of the affected limb. Infusion was practiced once a week, and repeated 4 to 6 times. MAIN OUTCOME MEASURES: Change in size of the affected limb (defined as the difference between the affected limb and the normal limb after treatment), and softening of the edema (measured with a tension gauge). RESULTS: In all 13 patients there was softening of the affected hard limb followed by a reduction in the size of the limb (mean 64%), and the ache and sensation of heat in the limb lessened. The reduction in size was maintained in 9 of the 13 patients for three months, despite returning to their normal activities. CONCLUSION: Intra-arterial infusion of autologous lymphocytes is a promising treatment for refractory lymphoedema. PMID- 8193208 TI - Malignant melanoma of the pancreas: primary tumour or unknown primary? PMID- 8193209 TI - Radiation-induced oesophageal cancer. PMID- 8193210 TI - Occlusion of the distal common bile duct after endoscopic sclerotherapy of bleeding duodenal ulcer. PMID- 8193211 TI - Whole body energy expenditure protein breakdown and polyamine excretion during high dose treatment with interleukin-2 and interferon-alpha. AB - OBJECTIVE: To correlate changes in whole body resting energy expenditure and protein breakdown with the production of stress hormones, excretion of polyamines, and circulating concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha), in patients undergoing treatment with high doses of interleukin-2 (IL-2) and interferon-alpha (IFN alpha). DESIGN: Prospective open study. SETTING: University Department of Surgery. SUBJECTS: 11 Patients with malignant melanoma (n = 8) or renal cell carcinoma (n = 3) all of whom had a Karnofsky score of 80 or more. INTERVENTIONS: Daily intravenous infusion of IL-2 (18 x 10(6) IU/m2/day) and subcutaneous injection of IFN-alpha (3 x 10(6) IU/m2/day) for days 1-5 and 8-12 in two courses with a three week interval. MAIN OUTCOME MEASURES: Energy expenditure measured by indirect calorimetry, body temperature, heart rate, urinary excretion of amino acids and nitrogen, and plasma cytokine concentrations. RESULTS: Three patients had a partial response. IL-1 was not detectable in plasma; and concentrations of IL-2 increased rapidly during the infusion before falling rapidly when it stopped, of IL-6 increased significantly (mean (SEM) 3.44 (1.6) to 11 (2) U/ml, p < 0.05), and of TNF-alpha increased by 295% (p < 0.05). Resting energy expenditure increased from 92 (4) to 113 (4) kJ/kg/day (p < 0.001) during the infusion and this was accompanied by a rise in temperature and an increase in the urinary excretion of cortisol (which also correlated with increased breakdown of whole body protein). CONCLUSION: The increased energy expenditure and protein breakdown were probably a result of stimulation of production of catecholamines and cortisol, as after injury, but the direct effects on temperature regulating neurons may be important. PMID- 8193212 TI - Effects of a combined drug regimen on tumour necrosis factor and plasma kallikrein activity in experimental endotoxaemia. AB - OBJECTIVE: To clarify the relationship between changes in haemodynamics, liberation of tumour necrosis factor and generation of plasma kallikrein, and to see if treatment with a combination of drugs was successful in preventing activation of tumour necrosis factor and plasma kallikrein in experimental endotoxic shock. DESIGN: Controlled study. MATERIAL: 22 juvenile pigs. INTERVENTIONS: 15 animals received 0.01 mg/kg endotoxin infusion, the rest being given the same volume of saline. 10 received no treatment, and 5 were given a combination of methylprednisolone, naloxone, ketanserin, promethazine, C1 esterase inhibitor, antithrombin III and aprotinin. MAIN OUTCOME MEASURES: Assessment of the liberation of tumour necrosis factor, generation of plasma kallikrein, and haemodynamic and cellular effects of endotoxaemia. RESULTS: There was a linear statistical relationship between decreases in cardiac output and increases in packed cell volume, and between increases in packed cell volume and plasma kallikrein activity. The combination treatment totally blocked all the effects of the infusion of endotoxin. CONCLUSION: Endotoxin affects several mediators, but combination treatment can prevent some of these effects. PMID- 8193213 TI - Influence of operation on glucose metabolism and lipolysis in human adipose tissue: a microdialysis study. AB - OBJECTIVE: To investigate the effect of an operation on metabolism in human adipose tissue. DESIGN: Open study. SETTING: Department of Surgery and the Research Centre at Huddinge Hospital. SUBJECTS: 13 non-obese patients who underwent elective cholecystectomy, and 5 control subjects. INTERVENTIONS: Microdialysis of the extracellular compartment of abdominal subcutaneous adipose tissue was done before, during and after a 45-minute intravenous infusion of 20 g glucose before, and one day after, the operation. MAIN OUTCOME MEASURES: Concentrations of glycerol, glucose, lactate and pyruvate in the tissue dialysate and in venous plasma. RESULTS: After operation, the baseline plasma insulin concentration doubled (p < 0.001) and the fasting glucose concentration rose from 4.4 (0.1) to 5.3 (0.2) mmol/l (p < 0.001). In response to the glucose infusion, the maximum increase in plasma insulin trebled (p < 0.01) and the integrated concentrations (area under the curve) of plasma glucose, lactate and pyruvate were significantly more pronounced (p < 0.02-p < 0.001) after than before operation. The suppression of plasma glycerol and free fatty acid concentrations was similar before and after operation (50-60%). The reduction in the concentrations of glycerol in adipose tissue, and the increases in the concentrations of glucose, lactate, and pyruvate, after intravenous infusion of glucose were not influenced by the operation. CONCLUSION: A moderately serious operation rapidly induces a deterioration in total body glucose homeostasis, partly as a result of peripheral insulin resistance. This does not affect the utilization of glucose by adipose tissue or the antilipolytic response to glucose infusion. PMID- 8193214 TI - Experimental evaluation of oxygen free radical scavengers in the prevention of reperfusion injury in skeletal muscle. AB - OBJECTIVE: To evaluate the role of oxygen-derived free radicals in reperfusion injury of skeletal muscle in rabbits. DESIGN: Open experimental study. SETTING: Department of experimental surgery. MATERIAL: 32 rabbits. INTERVENTIONS: Four groups according to pretreatment: group I: superoxide dismutase-superoxide scavenger; group II: catalase-hydrogen peroxide scavenger; group III: superoxide dismutase and catalase; group IV: mannitol-hydroxyl scavenger. Amputated hindlimbs were subjected to 4 hours of ischaemia followed by 2 hours of reperfusion. One limb was treated while the other served as a control. MAIN OUTCOME MEASURES: Muscle water content, energy charge, and muscle injury (uptake of 99mTc-methylenediphosphonate). RESULTS: Muscle water content was reduced in group III (p < 0.05) and IV (p < 0.05). Energy charge was improved in group IV (p < 0.05). Muscle injury was reduced in groups II (p < 0.05), III (p < 0.05), and IV (p < 0.01), but most in group IV (p < 0.01). CONCLUSION: Oxygen-derived free radicals seem to be mediators in reperfusion injury of skeletal muscle. The hydroxyl radical seems to be the most important of the xanthine oxidase-derived free radicals. PMID- 8193215 TI - Cost of growth in cells and organisms: general rules and comparative aspects. AB - In a crude fashion it can be said that metabolizable energy (M) is partitioned into metabolic work, paid for by 'oxidations' (R), and 'assimilation', i.e. production (P), so that M = R+P. However, a fraction of R is required to meet the expenses of production and if these expenses represent, Joule for Joule, a constant proportion of the amount produced, then Rt = Rm+cP, where Rt = total metabolic expenditures, Rm = metabolic expenditures for maintaining the non producing organism, and cP = Rp = metabolic expenditures connected with the processes of production. The partitioning of metabolizable energy into R and P as well as into Rm and Rp may vary depending on the phylogeny and life-history of the species concerned and on ecological circumstances. Thus selection is expected to act on both ratios, R/P and Rm/Rp. By comparing the ratios P/(P+Rp) (the apparent efficiency of production) and Rp/P (the apparent metabolic cost of production) in different types of organisms, one finds that a value of P/(P+Rp) = 0.75, equal to 75% efficiency, 10 mgdbm/mmol ATP, and 16 mumolO2/mg dbm (when I mg identical to 22 J), can be used as a 'consensus value' for the average efficiency, or cost, of the transformation of metabolizable energy into production in a wide range of organisms, from bacteria to mammals. This value corresponds to about three times the theoretical cost of synthesizing the same amount of tissue on the basis of known biochemical principles. The reasons why the empirical costs of production are higher than the theoretical costs of synthesis by what appears to be a common factor may be quite different in bacteria, small ectothermic and large endothermic organisms. Deviations from the consensus value may be due to differences in energy density of the nutrients assimilated and the tissues synthesized. Further complications arise because of interactions between P, Rp, and Rm. In microorganisms the existence of a constant and a variable component of maintenance metabolism has been postulated, the latter decreasing with increasing rate of production. In small ectothermic metazoans, on the other hand, the nonlinear relationship between growth metabolism and growth rate has led to the speculation that above a critical value of Pg certain energy consuming functions of maintenance are suppressed and the energy thus gained used for fuelling growth processes. There is some evidence that, at least in ectothermic metazoans, the apparent cost of growth decreases with the rate of growth, reaching a low plateau of about 10 mumolO2/mgdbm at growth rates exceeding about 8 mgdbm/g/h.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8193216 TI - Intraspecific variation in egg size and egg composition in birds: effects on offspring fitness. AB - 1. There is little unequivocal evidence to date in support of a positive relationship between egg size and offspring fitness in birds. Although 40 studies (of 34 species) have considered the effect of variation in egg size on chick growth and/or survival up to fledgling only 12 studies have controlled for other characters potentially correlated both with egg size and offspring fitness. Of these only two have reported a significant residual effect of egg size on chick growth (in the roseate tern and European blackbird) and three a residual effect on chick survival (all in seabirds: common tern, lesser black-backed gull and kittiwake). 2. More consistent evidence exists, though from fewer studies, for a positive relationship between egg size and offspring fitness early in the chick rearing period; chick growth and chick survival being dependent on egg size in 8 of 10 studies and 4 of 5 studies respectively. It is suggested that the most important effect of variation in egg size might be in determining the probability of offspring survival in the first few days after hatching. 3. Egg size explains on average 66% of the variation in chick mass at hatching (n = 35 studies) but only 30% of the variation in chick body size (n = 18). When effects of hatching body size are controlled for chick mass remains significantly correlated with egg size, though the reverse is not true. This supports the hypothesis that large eggs give rise to heavier chicks at hatching, i.e., chicks with more nutrient (yolk) reserves, rather than structurally larger chicks. 4. Egg composition increased isometrically with increasing egg size in about half the studies so far reported (n equals approximately 20). However, in seabirds, and some passerines, larger eggs contain disproportionately more albumen, whilst in some waterfowl percentage yolk content increases with increasing egg size. Changes in albumen content largely reflect variation in the water content of eggs, but changes in yolk content involve variation in lipid content, and therefore in egg 'quality.' The adaptive significance of variation in egg composition is considered; females may adjust egg composition facultatively to maximise the benefits to their offspring of increased reproductive investment. 5. Considerations for future research are discussed with particular emphasis on experimental studies and the application of new techniques. PMID- 8193217 TI - [The effect of the evening toilette on the quality of sleep in long-term patients]. PMID- 8193218 TI - [Women's careers in nursing]. PMID- 8193220 TI - [Patient management categories (PMC)--experiences in the surgical field]. PMID- 8193219 TI - [Structural model of practical mentoring. 2]. PMID- 8193221 TI - [Nursing models and guidance practice. 2]. PMID- 8193222 TI - [Synopsis of study courses in nursing at vocational schools and universities in the Federal Republic of Germany]. PMID- 8193223 TI - [Bacteremia, sepsis and spontaneous peritonitis by N. meningitidis serogroup B]. PMID- 8193224 TI - [Respiratory failure after administration of a high osmolarity radiological contrast media]. PMID- 8193225 TI - [Ferritin in Still's disease of the adult]. PMID- 8193226 TI - [Rhabdomyolysis and acute renal insufficiency in a patient with legionnaires' disease]. PMID- 8193227 TI - [Systemic mastocytosis]. PMID- 8193228 TI - [Metastatic pericardium adenocarcinoma resembling a primary pericardium tumor]. PMID- 8193229 TI - [Costoclavicular hyperostosis and palmoplantar pustulosis]. PMID- 8193230 TI - [Lumbosacral plexopathy from aortic aneurysm]. PMID- 8193231 TI - [Pure sensitive ictus due to thalamic cerebral hematoma]. PMID- 8193232 TI - [Usefulness of the detection of antigens and antibodies for the diagnosis of the infection by the human immunodeficiency virus]. PMID- 8193233 TI - [Immunogenetics of the Sjogren's syndrome in southern Spain]. AB - To establish the relation between HLA antigens, Primary Sjogren Syndrome (PSS) and autoantibodies production, in our geographical area, we undertook a case control study with a consecutive sample of 30 patients with PSS (Fox's criteria) attending in a reference hospital. Two hundred and sixty-four local controls with no apparent pathology were included for comparison. In patients we evaluated clinical and analytical aspects about multisystem autoimmune disease. Anti-SSA/Ro and -SSB/La autoantibodies were determined by double immunodiffusion. HLA typing was serologically determined. In logistic regression multivariate analysis, there were significant association between PSS and specificities HLA-Cw7 (73% in cases, versus 35% in controls; RR = 8.0; 95% CI: 23.2-2.7), HLA-DR3 (63% vs 20%; RR = 3.4; 95% CI: 9.5-1.4) and HL-DR11 (43% vs 13%; RR = 4.1; 95% CI: 12.0-1.4). In patients, the anti-SSA/Ro autoantibodies production were associated with HLA-DR3 antigen (83% vs 25%; RR = 6./; 95% CI: 1.3-34.2). All HLA-DQ2/DQ6 heterozygotes patients (8 cases) had anti-SSA/Ro autoantibodies, versus only one half of the remainder (p = 0.029; RR = 6.3). In anti-SSA/Ro negative patients there weren't association with HLA-DR3 antigen (33% vs 20%). HLA-DR3 were associated with the presence of anti-SSB/La autoantibodies, but there wasn't signification (p = 0.081). We conclude that our patients with PSS present association with HLA-DR11 specificity, that it's a risk factor for the disease development. HLA-DR3 would determined the anti-SSA/Ro autoantibodies, and maybe also anti-SSB/La autoantibodies, production. Furthermore, HLA-DQ2/DQ6 heterozygosity would determined immune response to SSA/Ro autoantigen. PMID- 8193234 TI - [The study of contacts of tuberculosis patients]. AB - The study and follow-up of contacts is one of the main goals of the battle against tuberculosis. We studied 640 contacts of 141 patients diagnosed of active pulmonary tuberculosis (PT) in our center between 1985 and June 1990. The average per index case (IC) was 4.5. Contacts were classified according to the IC bacteriology (positive bacilloscopy and culture: 448 cases; negative bacilloscopy and positive culture: 126 cases; and both tests negative: 66 cases). PPD was positive in 342 cases (53.4%) and the number of infected contacts was significant when IC showed positive bacilloscopy and culture (251 cases), cough (328 cases). Twelve new cases of tuberculosis (1.9%) were detected, with an average age of 29.6 years. Chemoprophylaxis was completed during one-year period by 121 contacts (43.5%). The systematic study of contacts allow us to detect new patients and infected cases, helping to break the epidemiological chain of transmission of the disease. PMID- 8193235 TI - [Study of hypercholesterolemia among the child population of Valdemoro]. AB - We studied 99 children with ages ranging from 0 to 14 years, randomly selected from the census of Valdemoro (Madrid) and stratified by sex and age. The clinical records of all the children were completed and the levels of total serum cholesterol were assessed. The average cholesterol level for the total sample was 159 +/- 31 mg/dl (m +/- sd). Twenty-six children (26.3%) had values above 175 mg/dl [75th percentile of the Lipid Research Clinics Program(LRCP)], with no significant differences between the values of such percentile in both studies. Ten per cent of the children showed cholesterolemias greater than 200 mg/dl. The average cholesterol level in children whose mothers had high education levels was 125 +/- 16 mg/dl (m +/- sd), versus 161 +/- 21 mg/dl (m +/- sd); p = 0.005; (CI 95% of the difference 12 to 62 mg/dl) in children whose mothers had low-medium education levels. Cholesterol in children with family history of hypercholesterolemia (HC) showed a non-significant trend towards higher levels than in children without such antecedents (164 mg/dl vs 155 mg/dl; p = 0.19; NS). Neither the differences were significant when comparing children with or without family history of early cardiovascular disease (ECDV) (162 md/dl vs 158 md/dl; p = 0.49). Using both familiar antecedents as misleading method, just 72% of the children were diagnosed of HC (cholesterol greater than 175 md/dl). The absence of both antecedents (negative VP) would discard the presence of HC in 83% of the children in such situation (CI 95%, 67% to 92%). PMID- 8193236 TI - [Infection by Salmonella typhi in the southern area of Ponteverde]. AB - A retrospective study of patients infected by Salmonella typhi (ST) was conducted in the southern area of Pontevedra during a 17-month period in order to assess the clinical and evolutive characteristics and the pattern of antibiotic susceptibility of the infection. ST was isolated from samples of 30 patients: 25 hemocultures, 7 coprocultores, 1 urine and 1 aortic aneurysm. Nineteen cases had consumed non-sanitary controlled water, 95% from rural areas. The clinical characteristics were similar to the ones traditionally described. Seven patients (23%) developed complications and their presence was associated to a poorer prognosis. We did not observe any resistance to the commonly used antibiotics. In summary, the infection by ST is still a health problem in our environment, probably associated to insufficient measures in the enloration of water for human consumption. PMID- 8193237 TI - [Jaundice secondary to intrahepatic deposit of light chains as a presenting form of multiple myeloma]. AB - In the disease caused by deposit of light chains, nephropathy is the earlier and most frequent clinical manifestation; and although the liver is the extrarenal organ most frequently affected, its affection is rare without renal deposit of light chains. Bearing this in mind, we present the clinical and evolutive characteristics of a patient diagnosed of IgG Kappa multiple myeloma, whose first manifestation was a jaundice syndrome with intrahepatic deposit of light chains documented in the anatomopathologic study and in which, despite presenting renal failure, deposits of light chains were not observed in the renal biopsy. We review the medical literature on this topic. PMID- 8193238 TI - [Visceral and cutaneous Kaposi sarcoma in a patient with rheumatoid arthritis under steroid treatment]. AB - We present the case of a patient under corticosteroid therapy (Deflazacort) developing a cutaneous Kaposi's Sarcoma. In a latter study performed due to the presence of digestive syndrome, a gastric Kaposi's sarcoma was detected. We review the cases published in the literature of patients with rheumatoid pathology under corticosteroid therapy. PMID- 8193239 TI - [Pheochromocytoma secreting adrenaline, a rare form of presentation]. AB - We present the case of a 42-year-old patient with a pheochromocytoma, whose clinical form of presentation was extremely rare, due to the high secretion of adrenalin compared to noradrenaline. We stress the relevance of the anamnesis for the diagnosis of this pathology, as well as the problems regarding its clinical, anaesthetic and surgical management. In addition, we review the literature. PMID- 8193240 TI - [Asymptomatic polymyositis with pulmonary disease]. AB - We present the case of a medium-aged patient with a alveolo-interstitial pulmonary affection after 5 months of evolution, characterized by cough and progressive dyspnea accompanied by sustained febricula, slight constitutional syndrome and dermatological and articular manifestations. It was finally concluded that the patient had a polymyositis, relating form of affection a secondary interstitial pneumopathy. The aim of this study has been to highlight a rare case of diffuse interstitial disease in the context of a polymyositis in which we obtained an excellent therapeutical response, as well as to make some considerations regarding its etiology and its clinical and pathological expression. PMID- 8193241 TI - [Cavitated lung pneumonia due to meningococcus]. AB - Neisseria meningitidis is a common germ of the respiratory pathways which seldom produces pulmonary infection. Some established cases of pneumonia by meningococcus and, exceptionally, of complications like the empyema, have been described. However, just one case of cavitated pneumonia by N. meningitidis has been described in the medical literature. We present a case of pneumonia with cavitation produced by N. meningitidis, which was diagnosed through fibrobronchoscopy with transbronchial biopsy. This observation is of very high clinical interest, because N. meningitidis is a pathogenic agent which is not taken into account for the differential diagnosis of cavitated pneumonias. PMID- 8193242 TI - [Physiopathology of hypophyseal tumors secreting growth hormone, prolactin and glycoproteins]. PMID- 8193243 TI - [Multiple symmetric lipomatosis]. AB - Multiple Symmetric Lipomatosis (MSL or Madelung's Disease) is a rare entity characterized by the presence of non-capsulated lipomas mainly located at the neck and upper part of the thorax and frequently associated to chronic hepatopathy, neuropathy and alcoholic habit. We review and update the clinical, etiopathogenic, diagnostic and therapeutical aspects of this rare entity. We stress the presence of neuropathy, a typical feature of the disease, which has also a predictive value. PMID- 8193244 TI - [Reduction of NMR image artefacts by using optimal materials as diagnostic aids and implants]. AB - Differences in magnetic susceptibility, as occur for example at the boundary between implant materials and the surrounding body tissue, result in artefacts and a signal loss in magnetic resonance imaging. By using materials with a magnetic susceptibility matched to the respective environment, it is possible to minimize both artefacts and signal loss. Such materials can be made by combining two materials of different magnetic susceptibility (e.g. diamagnetic and paramagnetic materials) in such a way that the resulting material has the desired effective magnetic susceptibility. PMID- 8193245 TI - [Sound frequency analysis for identification of venous air embolism]. AB - Air emboli occurring during surgery are considered to be life-threatening incidents. With the aim of achieving acoustic identification of venous air emboli, a frequency analysis of the sounds induced by an air embolism (millwheel murmurs) as well as of all other unusual sounds, was undertaken during 20 operations, and in experiments with animals. The frequency spectra of the sounds induced by air emboli are characterised by an increase in the amplitudes in the frequency range 1,100 to 3,000 Hz, while the amplitudes of normal heart sounds continuously decrease with increasing frequency. The frequency spectrum was examined for characteristics using an electronic filter system. The sounds induced by air emboli can be clearly distinguished from normal heart sounds. During operations on patients, suction sounds occur, the frequency patterns of which are not easy to distinguish from those of embolus-induced sounds, although an acoustic distinction can be made via a stethoscope or a loudspeaker. With optimal adjustment of the filter system, 73 out of 81 (90%) embolism-related sounds were correctly identified in animal experiments. On no occasion were normal heart sounds wrongly identified as due to an embolus. However, an embolus sound was frequently mimicked by interfering sounds such as those produced by artificial respiration, and other ambiend sounds. By modifying the oesophageal catheter to achieve optimal suppression of interfering sounds, this filter system could be developed into an alarm. PMID- 8193246 TI - [A method for determining pulse wave transmission time]. AB - Analysis of the transit time of a pulse wave is a possibility for the continuous observation of the changes in blood pressure activity. With invasive procedures, the interval between two notable events on pressure pulse waveforms, which is known as the pulse transit time, is often calculated. Using the second heart sound, the pre-ejection period and the left-ventricular ejection time (systolic time interval) are computed in order to be able to exclude the effect of haemodynamic parameters on aortic pressure increase. Since the use of noninvasive procedures excludes computation of the systolic time interval, and a phonocardiography is also often lacking, a method of relatively quickly determining the time interval between the R-wave of the ECG and the peripheral pulse was developed. The computed pulse transmission time is suitable for studying phasic events and their effects on the mean blood pressure. PMID- 8193247 TI - [A respiratory microvalve for spontaneously breathing anesthetized small animals]. AB - For the accurate functional analysis of the gas exchange in the lungs or evaluation of artificial oxygen carriers in spontaneously breathing anaesthetized small animals, we developed a new respiratory micro-valve. The body of the valve is made of aluminium, and the flaps are made of silicone rubber. The maximum flow rate in a rat measured with a pneumotachograph and the micro-valve was an average of 19.9 ml/s during inspiration, and 17.8 ml/s during expiration. The pressure measured in the tracheal tube was -0.85 during inspiration, and +0.39 cm H2O during expiration; the end-expiratory pressure in the tube was zero. In two experiments with anaesthetised rats lasting 4-5 hours, ventilation, oxygen uptake, carbon dioxide release and the respiratory exchange ratio were 638 ml/min/kg, 21.7 ml O2(STPD)/min/kg, 16.6 ml CO2(STPD)/min/kg, and 0.77, respectively. There was no significant change in any parameter during the experiment. The micro-valve increases the dead space by approximately 35%, but this is well tolerated by the rats, which compensate by increasing their tidal volume by about 10 to 15%. The major advantage of using the micro-valve in comparison with other methods is the fact that the true difference between inspiratory and mean mixed expiratory gas can be measured with great accuracy. The micro-valve can readily be adjusted for optimal use with a range of animals. PMID- 8193248 TI - Simplifying in-vitro fertilization therapy. PMID- 8193249 TI - The effect of aging on fertility. AB - In the developed world, deferment of marriage and postponement of child-bearing in marriage are resulting in unprecedented numbers of couples who desire pregnancy relatively late in life. These factors combine with a decline in fertility and an increase in pregnancy wastage with advancing age to present new challenges for the clinician treating infertility. Experience with young oocytes donated to older women indicates that the major responsibility for the decline in fertility with age can be attributed to aging oocytes. Oocyte donation offers new hope for infertile older woman, but important moral and social questions remain unanswered. PMID- 8193251 TI - Pathophysiology of human spermatozoa. AB - Our capacity to diagnose the functional competence of human spermatozoa has been facilitated by recent advances in our understanding of sperm physiology. This review focuses on two important developments, namely the role of lipid peroxidation in the pathophysiology of impaired sperm function and the extragenomic action of progesterone in controlling sperm activation. PMID- 8193250 TI - Corpus luteal insufficiency. AB - The corpus luteum is controlled by luteinizing hormone (LH) and intraovarian morphofunctional specialization and autocrine/paracrine mechanisms. Corpus luteal insufficiency produces luteal phase defects (LPD). The poor precision and validation of endometrial histologic dating and single or random multiple serum progesterone measurements produce widely variable diagnoses. The true prevalence rate of LPD may be only 3-5% similar to that due to chance. The role of LPD in causing infertility can be challenged because the diagnosis is not predictive of recurrence in subsequent cycles, and other causes of infertility are not controlled for. Intraobserver and interobserver variability, uterine site of biopsy, luteal phase length, time of ovulation, and luteal phase timing of biopsy have been examined and have confirmed the imprecision of dating as a sensitive and reliable assessment of luteal insufficiency. There is support for either early or late luteal phase biopsy. Endometrial dating using LH timing as a reference point is relatively more reliable. Integrated luteal progesterone is the only currently accurate assessment of luteal sufficiency. Clomiphene does not increase LPD but increases serum progesterone, integrated progesterone, corpus luteum LH/human chorionic gonadotropin (hCG), and insulin-like growth factor-1 (IGF-1) receptors, all of which promote increased progesterone production and do not affect endometrial estrogen and progesterone receptors. hCG is more likely to stimulate progesterone production if given at the mid rather than early luteal phase corresponding to the phase with highest total and available (unoccupied) corpus luteal LH receptors. Careful analysis of published studies on treatment of LPD revealed only one randomized controlled study, and, statistically, all studies revealed no better outcome with progesterone treatment. PMID- 8193252 TI - Advances in induction of ovulation. AB - The emphasis of this review is placed on the treatment of clomiphene-resistant women with polycystic ovary syndrome (PCOS) or with hypogonadotropic hypogonadism. There has been an increasing awareness of the need to avoid the consequences of multiple folliculogenesis, and this is reflected in the more widespread use of low-dose regimens for induction of ovulation, particularly in PCOS. The past 12 months have seen the first reports of the clinical applications of recombinant human follicle-stimulating hormone (FSH), and there is an intriguing suggestion that long-acting opiate agonists may have a part to play in the management of anovulation of hypothalamic origin. PMID- 8193253 TI - Laparoscopic surgery for infertility therapy. AB - This review provides an update on the role of operative laparoscopy in infertility treatment. The areas of discussion include laparoscopic surgery for proximal and distal tubal disease, polycystic ovarian syndrome, endometriosis, and assisted reproduction. PMID- 8193254 TI - Medical and surgical treatment of ectopic pregnancy. AB - Laparoscopic removal of the products of conception remains the treatment of choice for ectopic pregnancy (EP). Systemic administration of methotrexate (MTX) is a promising new treatment; however, its efficacy has to be established in clinical trials. Local treatment by laparoscopy with MTX, prostaglandin, or other substances is not as effective as laparoscopic salpingostomy. PMID- 8193255 TI - Issues in the etiology of recurrent spontaneous abortion. AB - Recurrent spontaneous abortion is seen often. Although many causes of this condition have been identified, there is still a large proportion in which no cause can be found. This review highlights some of the newly described proposed causes. Several reports have linked reproductive inefficiency to hypersecretion of luteinizing hormone (LH) in the follicular phase. It is apparent that the presence of inappropriate elevation of LH, and not the ultrasonographic appearance of polycystic ovaries, is the critical factor in determining the risk of abortion. Consequently, by lowering the LH levels one can expect a better reproductive outcome. This hypothesis awaits testing through clinical trials. The role of ultrasonography in evaluating the luteal phase, by assessing the image of the endometrium, has been studied by many investigators. This non-invasive technique is not yet able to replace the endometrial biopsy. The association between antisperm antibodies in the female serum and recurrent spontaneous abortion requires re-evaluation in light of more recent evidence; however, the role of semen abnormalities, especially severe oligospermia in this disorder, points towards a factor in the male partner that should be identified. Oligomenorrhea has been identified by mathematical modeling as a potential risk factor for recurrent abortion, although the mechanism has not been clearly elucidated. Chromosome heteromorphisms, particularly inv (9)(p11 q12), appear to be associated, more frequently, with recurrent abortion. Similarly, associations were observed with factor-XII deficiency and high titers of immunoglobulin G (IgG) antibody to Chlamydia trachomatis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193256 TI - Oocyte donation--implications for fertility treatment in the nineties. AB - In the past decade, oocyte donation has become a widely used assisted reproduction technique with reported pregnancy rates often higher than those for conventional in-vitro fertilization. Recipients of donated oocytes include women with premature ovarian failure or severe genetic disorders, those who respond poorly to ovarian hyperstimulation, women over 40 years of age, and, recently, postmenopausal women. The donation of oocytes to older women raises many medical and social issues which have to be addressed. PMID- 8193257 TI - Luteinizing hormone-releasing hormone agonists for ovarian stimulation in assisted reproduction. AB - Although the use of luteinizing hormone-releasing hormone (LHRH) agonists and human menopausal gonadotropin (hMG) for ovarian stimulation in assisted reproduction has gained widespread popularity, a number of major issues regarding their use remain unresolved. Some of these issues are examined in the light of recent developments. The routine use of LHRH agonists produces significantly higher pregnancy and livebirth rates compared with conventional methods of ovarian stimulation. A number of prospective, randomized studies have shown that the long protocol of LHRH agonist administration is superior to the short and ultrashort protocols, and it appears that early follicular phase initiation of the long protocol may be particularly beneficial. Another major advantage of the long protocol of LHRH agonist administration is that, with its use, precise timing of human chorionic gonadotropin (hCG) administration is not important. It would, therefore, appear that the routine use of LHRH agonists has both medical as well as practical advantages. PMID- 8193258 TI - IVF and micromanipulation techniques for male-factor infertility. PMID- 8193259 TI - Transcervical tubal transfer of gametes and embryos. AB - The benefit of intrafallopian transfer techniques is still disputable in assisted reproductive techniques. On this background, alternatives to laparoscopic transfer procedures are in development. Current transcervical intrafallopian transfers of gametes and embryos are lacking success and reproducibility of results. New developments in catheter techniques and optical systems are offering new concepts for more successful transcervical approaches and preparing the basis for truly prospective studies. PMID- 8193260 TI - Fertilization and implantation. AB - Recent advances in seemingly remote areas of investigation, i.e. yeast cell cycle research and DNA amplifications, have opened spectacular avenues for understanding reproduction. The new insights on the single cell and subcellular level of processes, such as egg maturation, sperm-egg interaction and implantation enhance, immensely, the power of assisted fertilization. These techniques, have become the mainstay of infertility therapy. This review focuses on the recent developments in these areas. PMID- 8193261 TI - Results and complications of IVF therapy. AB - This review attempts to discuss the current efficacy of in-vitro fertilization (IVF) treatment, factors influencing IVF success rates, and complications of IVF therapy. The livebirth rate per oocyte retrieval and per embryo transfer (ET) have been among the most widely used indices of success. To determine true efficacy, success rates have to be related to patient characteristics, such as age and cause of infertility. The cumulative conception rate after specified periods of treatment provides the most useful estimate of success rate after IVF. Approaches to further improving IVF treatment in the future are discussed. Considering the ongoing scientific research in the field of assisted reproduction, it should be the challenge of the nineties to further improve IVF success rates per treatment cycle by 50-100%. PMID- 8193262 TI - Diagnosis and management of fetal neuroblastoma. AB - At 36 weeks' gestation, in a 30-year-old patient, routine prenatal ultrasound examination revealed a cystic mass in the left adrenal gland. The pregnancy was uneventful, and at delivery the infant had a palpable left flank mass confirmed by ultrasound and computed tomography scan. There were no metastases. On the second day of life, a 5 cm cystic stage-I neuroblastoma was removed by adrenalectomy. The infant had an uneventful recovery, required no further treatment, and remains free of disease 26 months later. PMID- 8193263 TI - Suppression of EJ cells tumorigenicity. AB - Ribozymes, site-specific ribonucleases, are a new vehicle for the manipulation of gene expression. A hammerhead ribozyme designed to cleave the GUC sequence in codon 12 of activated H-ras RNA was cloned into a plasmid (pH beta Apr-1) and transfected into EJ human bladder carcinoma cells. Expression of the ribozyme dramatically reduced H-ras gene expression and inhibited growth of EJ transformants in vitro. In vivo, the H-ras ribozyme suppressed EJ cell tumorigenicity in nude mice. In contrast, the insertion of a mutant ribozyme with no demonstrable cleavage capacity into EJ cells resulted in smaller reductions in H-ras gene expression and growth inhibition while also suppressing tumorigenicity in nude mice. The ribozyme's effect on tumorigenicity was stable, as the cells were cultured for up to five months in vitro prior to injection into nude mice. These studies define a role for anti-oncogenic ribozymes as a unique class of tumor suppressing agents. PMID- 8193264 TI - Natural course and trial of treatment for infantile liver dysfunction associated with cytomegalovirus infections. AB - Human cytomegalovirus (HCMV) has been reported as one of the etiologic agents of neonatal and infantile hepatitis, although the pathogenic role of HCMV in hepatitis has yet to be clarified. In this study, we observed the natural courses of liver dysfunction associated with HCMV infection and assessed the effects of oral administration of glycyrrhizin (GL) to patients who had histories of prolonged liver dysfunction and poor body weight gain. Liver dysfunction in these cases clearly improved after administration of GL. GL administration is considered to be one of the suitable treatments for improving liver dysfunction in patients with HCMV infection. PMID- 8193265 TI - Analysis of the antimetastatic effects of synthetic muramyl tripeptide (CGP 19835A) encapsulated in liposomes in combination with other immunomodulatory agents and chemotherapeutic drugs. AB - The synthetic molecule muramyl tripeptide (CGP 19835A) encapsulated in liposomes is effective in increasing the survival of mice with spontaneous experimental lung metastases induced by the RENCA renal adenocarcinoma and B16 melanoma tumor models. The present study was aimed at extending the effects of CGP 19835A to another highly metastatic carcinoma model and at evaluating the efficacy of combination therapy with standard cytotoxic agents and other immunomodulators. C57BL/6 mice received whole tumor implants of PancO2, a spontaneously metastasizing pancreatic adenocarcinoma, subcutaneously in the hind leg. Therapeutic effects were measured by increased survival which is a direct function of the growth of spontaneous lung metastases in this system. No therapeutic efficacy was observed with CGP 19835A alone or in combination with any of a series of cytotoxic or biological agents, including cis-platinurn (cis Pt), mitomycin C (MMC), adriamycin (ADR), cyclophosphamide (CP), interferon gamma (IFN gamma), and interleukin 2 (IL-2). In accord with previous studies, when the B16-F10 melanoma was used as an experimental metastatic tumor model, CGP 19835A, alone and in combination with CP, significantly reduced the number of pulmonary metastases. Cis-Pt, however, partially negated the effects of CGP 19835A when a combination of the two agents was used. The results indicate that CGP 19835A is an effective therapeutic agent in some models of spontaneous or experimental lung metastases, but not others, and that the effects of CGP 19835A are not enhanced by the accompanying cytotoxic drugs tested here. PMID- 8193266 TI - Neuropathological changes induced by total cerebral ischemia (TCI) in a new experimental model. AB - We describe a new model of human ischemia encephalopathy in rabbits by means of cross-clamping the ascending aorta in combination with blood exsanguination from the right atrium. Rabbit hippocampal CAI pyramidal cells and cerebellar Purkinje cells showed only a few changes in the early period after ischemia, but 4 days after ischemia a significant decrease in cell count and marked degeneration of the remaining cells were observed. When the pathological findings 4 days after TCI in the hippocampal area and cerebellar area were compared, the rate of cytoclasis was found to be significantly higher in the latter than in the former. PMID- 8193267 TI - Halothane-induced cytotoxicity in isolated rat hepatocytes: an electron microscopic study. AB - To determine the direct cytotoxicity of halothane for liver cells, the effects of this agent on isolated rat hepatocytes were investigated by electron microscopy and by examining cell viability. Soon after treatment with lower concentrations of halothane (0.5% and 0.75%), there were marked changes in the plasma membrane. Cell viability was reduced to 70% of the control. At higher concentrations of halothane (1% and 3%), degeneration of mitochondria was noted. Cell viability was reduced to 40% of the control. Halothane, at lower concentrations, appeared to induce early morphological alterations of the plasma membrane, while higher concentrations damaged the organella. PMID- 8193268 TI - Distribution and kinetics of 131I-labeled human IgM monoclonal antibody 16.88 in patients with advanced colorectal cancer. AB - Sequential immunoscintigrams were used to describe the relative distribution and kinetics of 8 mg 131I-labeled human IgM monoclonal antibody 16.88 in 20 patients with colorectal cancer. The results show that the initial activity was higher and the clearance rate was faster (P < 0.05) from the left ventricle and liver than from most organs. In bone marrow the reverse was observed (P < 0.05). The biological half-life of 131I(-16.88) in tumor tissue (range 35.4-47.5 h) was longer (P < 0.01) than that in normal tissue (30.2-41.9 h). The image contrast ratio between liver metastases and background increased from 0.8 to 1.3 and for lesions outside the liver from 1.1 to 1.6. The estimated effective dose equivalent was 0.12 mSv/MBq. A second infusion 2 weeks after the first with the addition of unlabeled 16.88 up to 1000 mg for improvement of tumor tissue uptake was not of clinical relevance. PMID- 8193269 TI - Growth interaction between different tumor populations in human endometrial adenocarcinoma growing in nude mice. AB - In these studies of tumor cell growth interaction we have used two tumors differing from each other in sensitivity to estradiol, transplanted to opposite sites of the same nude mice. In the first experiment we found that the growth of an estradiol-sensitive tumor may be delayed by the presence of an estradiol resistant tumor in the same animal. Although the growth pattern was changed, proliferative activity, as reflected in the S-phase fraction measured by flow cytometry, and the steroid receptor concentrations were unchanged. Increase of circulating estradiol, however, protects the estradiol-sensitive population from this down-regulation of growth. Findings in a second experiment suggest that this growth delay is probably caused by changes such as decrease in labelling index, increase of non BrdU-incorporating cells in the S-phase, and cell loss in estradiol-sensitive tumors. We concluded that the estradiol-resistant tumor population may secrete some factor(s) acting as endocrine product(s) which may delay the growth of estradiol-sensitive cell populations when the tumors are grown in an estradiol-poor environment. If our model also represents interactions between tumor subpopulations within a single tumor, these findings may have implications for our understanding of the biology of tumor progression in some hormone-related human tumors. PMID- 8193270 TI - Modulation of doxorubicin efficacy in P388 leukemia following co-administration of verapamil in mini-osmotic pumps. AB - Co-administration of doxorubicin and verapamil in Alzet mini-osmotic pumps increased the survival of B6D2F1 mice bearing the multidrug-resistant P388/ADR leukemia. A range of doxorubicin and verapamil combinations was studied to define dose-dependent efficacy and toxicity. High doses of doxorubicin (10 mg/kg/day) and verapamil (150 mg/kg/day) could be administered alone without any effect on survival. However, combining high doses of these two agents resulted in host toxicity. Doxorubicin doses of 1 to 10 mg/kg/day in combination with verapamil at 25-100 mg/kg/day were found to improve survival compared with either agent alone. Combination therapy also improved the survival of mice bearing the drug-sensitive P388/0 leukemia when compared to anthracycline treatment alone. The efficacy of the mini-osmotic pump delivery protocol was compared with other regimens delivering the same total cumulative dose of doxorubicin via repeated i.p. injections. PMID- 8193271 TI - Experimental induction of uterine adenocarcinoma in rats by estrogen and N-methyl N-nitrosourea. AB - To induce uterine endometrial adenocarcinoma, Donryu rats were given subcutaneous injections of 100 micrograms/kg estradiol dipropionate (ED) four times once a week from 3 months old, followed by weekly intraperitoneal injections of 20 mg/kg N-methyl-N-nitrosourea (MNU) four times. In the ED+MNU group, the incidences of marked hyperplasias and adenocarcinomas were higher than those in the control and ED or MNU alone groups, when the incidences were compared in survival cases only up to the age of about 15 months, while the survival rate showed a specially low value of 35% in this group. These results may suggest the possibility of early and high occurrence of uterine adenocarcinoma in this rat strain by estrogen and MNU. PMID- 8193272 TI - Detection of the cytomegalovirus by the polymerase chain reaction DNA amplification in a kidney transplanted patient. AB - Cytomegalovirus injection is common in kidney transplanted patients. Viremia is the only marker of active CMV infection, but the use of cell culture for the direct detection of the virus is time-consuming and not very sensitive, while the detection of CMV by measuring the titre of antibodies is difficult due to the immunosuppression these patients undergo. Thus the ability to amplify CMV DNA by the polymerase chain reaction from blood or urine samples of the patients becomes a valuable diagnostic tool for the detection of CMV in the early stages of the infection. Using a set of primers specific for the amplification of a 435 bp region of the IE-1 gene, we detected CMV DNA in blood leucocytes of a kidney transplanted patient who received the transplant from a CMV-seropositive donor, 45 days after the operation, while the antibody titre showed no evidence of active CMV infection. PMID- 8193273 TI - Diabetes mellitus is controlled by vitamin C treatment. AB - The present study was started to investigate the question of whether or not vitamin C administration may help control diabetes mellitus (DM) by stimulating the insulin mechanism of a DM patient. We were motivated to take up the above thesis by the anticipation that vitamin C, being detectable in abundance in endocrine cells, may play a cardinal role in the production of hormones. In the preliminary experiment, we investigated the relation between glucose, insulin and vitamin C in the plasma of a non-diabetic male volunteer in whom vitamin C was introduced intravenously either by injection or by infusion, and with or without concomitant administration of glucose. In the follow-up study of 3 DM patients, the effect of the vitamin C infusion therapy on DM was assessed by summing up multiple clinical information. Results obtained are as follows: 1) the drip infusion system was superior to the ordinary injection system for maintaining plasma concentration of vitamin C at a high level and for a long period. 2) The plasma concentration of insulin, when tested in the vitamin C infusion system, followed a bimodal curve--a finding to suggest that vitamin C may stimulate the insulin mechanism in 2 distinct ways. The early mode was glucose-dependent at its height, but the late mode was independent of glucose charge. 3) The praxis of vitamin C infusion produced clinical improvements in 3 DM patients. The therapeutic efficacy of the treatment varied from patient to patient. In all cases, control of DM was started by combined use of the vitamin C infusion treatment and the insulin injection treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193274 TI - Effect of naftidrofuryl and aspirin on platelet aggregation in peripheral vascular disease. AB - Platelet aggregation in whole blood (WB) was assessed in healthy subjects and in patients with peripheral vascular disease (PVD) using a WB-free platelet counting (WB-FPC) method. Aggregation induced by stirring and platelet agonists was significantly enhanced in PVD patients. WB-FPC aggregation induced by 5-HT was diminished significantly by incubation with naftidrofuryl (NAF) in WB of PVD patients. In contrast, aspirin (acetylsalicylic acid; ASA), added in vitro, did not significantly affect 5-HT or stirring-induced WB-PFC aggregation in PVD patients. Furthermore, 5-HT-induced WB-FPC was inhibited by NAF in blood collected from PVD patients that were taking low dose aspirin. These findings suggest that NAF may be of benefit to patients with hyperaggregable platelets and elevated plasma 5-HT concentrations, factors thought to predispose to thrombotic complications. PMID- 8193275 TI - Compromise in the treatment of hirsutism with flutamide. AB - The association of Flutamide (500 mg/day) and of a contraceptive pill has been proposed for the treatment of hirsutism but the efficacy of low doses of the antiandrogen as single medication has never been ascertained. Twelve adult hirsute women, aged 31-40 years, were therefore recruited because they were sterile following tubal ligation. Severity of hirsutism was evaluated according to Ferriman and Gallwey scale. After one year, 10 out 12 patients experienced a satisfactory control of their hirsutism with Flutamide dosages varying between 250 and 375 mg/day. The antiandrogen can thus be used at lower dosages than initially expected. PMID- 8193276 TI - Therapeutic possibilities and opportunities for comparative oncopathology. AB - In reviewing abnormal growth, we may distinguish autonomous and nonautonomous growth processes. The highest diversification is reached in the autonomous non self-limiting processes, the malignant neoplasms which, if not treated, are characterized by extensive growth and progression. In their development these processes exhibit autonomy on one hand and heterogeneity on the other. Neoplastic and related diseases are extremely complex. It is unacceptable to view them exclusively as genetic or metabolic diseases, or merely as the tumor itself, including its progressive stages, as evidenced in neoplastic metastasis. All these characteristics appear in the different types of neoplastic malignomas, e.g. genetic variations in the neoplastic cells from the normal cells of the parent tissue(s). Included here are tumor progression and cloning of the neoplastic cells, stagewise development of host metabolism and of tumor metabolism; neoplastic hereditary and endocrine-like syndromes as well as paraneoplastic syndromes and cachexia. Neoplastic progression, as observed in the metastatic cascade, derives from the cells of the primary tumor. In contrast, multiple primary tumors originate from different host tissues, whereas the syndromes themselves constitute a symptom complex developing in a neoplasm bearing host and cannot be assigned to local or distant spread of neoplasms. The only possible explanation for these apparently contrasting processes lies in the interaction of tumor and host metabolism, which seemingly varies in tumor-bearing hosts and in those cases where the tumor has been surgical removed. Antigens and other compounds again show an increase with the usually ensuing secondary tumor spread, a course which provides the basis for most deaths from cancer. PMID- 8193277 TI - CMV induced vascular injury: an electron-microscopic study in the rat. AB - There is evidence in support of a viral etiology for atherosclerosis. In our study, we demonstrated that cytomegalovirus (CMV) infection in rats caused morphological alterations of the endothelium and subendothelial space of the large vessels and that these alterations are similar to those which are induced by hypercholesterolemia. These alterations consisted of swollen endothelial cells with a surface showing bleb and microvilli formation. In addition, adhesion of leukocytes to the endothelium and the presence of leukocytes (lymphocytes and macrophages) in the subendothelium were found. Lipid accumulation occurred in the endothelium and in the subendothelial space, especially in hypercholesterolemic animals. This lipid accumulation in the subendothelial space consisted of extracellular lipid deposition and of subendothelial located "foam cells". A characteristic phenomenon of the effect of CMV infection of rats was a loosening of the endothelial cells from the basement membrane. The space between the basement membrane and endothelium was expanded and was filed with an increased amount of reticular basal lamina-like material. These observations show that CMV infection is associated with a non-deniding aortic endothelial injury which is consistent with the early events in the process of atherosclerosis. PMID- 8193278 TI - Chemoprevention of breast cancer. AB - Chemoprevention of cancer is a new branch of the medical science and represents a topic of increasing concern in public health. Over the last decade chemoprevention has been extensively studied from many points of view, and topics in the field of chemoprevention have expanded considerably. Breast cancer, the most common malignant neoplasm in women, is one of the areas of clinical interest for chemoprevention. In this paper the authors synthesized the "status of art" in chemoprevention of breast cancer with retinoids and antiestrogens. PMID- 8193279 TI - Ten years of tumor imaging with labelled antibodies. AB - Since more than a decade scientific and clinical interest has centered on indicator proteins, most of which have been commercialized as tumor markers. Since many of these substances are cell membrane bound, they have served also as target substances for tumor imaging with nucleide-labeled antibodies. Although this technique, which is called radio-immuno-detection (RID), has made huge progress during the last ten years, it is still not a routine procedure employable in any department of nuclear medicine. It needs experience both for the interpretation of the images and the choice of the tumors to be investigated by this method. It remains, nevertheless, that radio-immuno-scintigraphy is a simple, easy-to-handle and low-cost technique with no harmful side-effects on the patient. PMID- 8193280 TI - Biological response modifiers as adjuvants in monoclonal antibody-based treatment (review). AB - Compelling experimental evidence suggest that the use of differentiation-inducing agents which enhance tumor antigen expression may play a pivatal role in MAb based approaches to tumor diagnosis and/or therapy. In particular, interferons can up-regulate CEA and TAG-72 expression on the surface of human carcinoma cells which leads to an enhanced MAb tumor localization. The ability to target additional MAb to the tumor site has subsequently been shown to augment radioimmunodetection and therapy in experimental models. Initial clinical studies reported that interferon administration to patients diagnosed with malignant melanoma improved the tumor distribution of antimelanoma MAb without an accompanying increase of antibody in normal tissues. The findings from our phase 1A trial clearly showed that intracavitary IFN-gamma administration augmented TAG 72 and CEA expression on carcinoma cells isolated from malignant ascites from patients diagnosed with ovarian or gastrointestinal cancer. Future efforts need to further investigate the molecular mechanisms involved in the regulation of these and other human tumor antigens by the interferons as well as other differentiation-inducing agents. Additional clinical studies should evaluate the overall effectiveness of combining an antigen up-regulation protocol with a conjugated MAb in the hope of improving tumor diagnosis and therapy. PMID- 8193281 TI - Serum marker combinations in human breast cancer (review). AB - Breast cancer markers (TM) are mainly useful for monitoring the course of disease after diagnosis and first line treatment with the control options of primary treatments early recognition of reactivation and efficiency control of palliative treatment. The best single and established marker is a polymorphic epithelial mucin of the MUC-1 family the prototype of which is CA 15-3 (successive markers: MCA, CA-549, TAG-12, CAM 26/29) followed by CEA with lower diagnostic sensitivity and specificity and TPA/TPS reflecting more the proliferative activity. Besides former TM combinations of CEA with one or more less specific markers (e.g. PAM, CRP, beta 2m, ferritin, GCDFP, HCG, total or boney AP, gamma GT), more recent studies recommend the use of fewer markers such as TPA/TPS + CEA or CA 15-3, CA 15-3 + CEA or MCA, CA M26 + CA M29, TAG12 + CA 15-3 + MCA and CEA + CA 15-3 + ESR. PMID- 8193282 TI - Clinical value of radiolabeled monoclonal antibodies in the management of carcinoma patients. AB - A significant number of monoclonal antibodies, suitable for in vivo management of carcinoma patients, have been recently developed and evaluated in clinical trials. They can be used successfully either for imaging or for radioimmunotherapy, although their clinical application shows advantages and limitations. With the advent of genetic engineering, it has become feasible to design molecules (i.e. chimeric and humanized antibodies, single-chain) to circumvent drawbacks or enhance a certain property. Several radionuclides can actually be used to be linked to monoclonal antibodies, including radiometallic isotopes which need bifunctional chelators. Coupling these radiometals to proteins will greatly increase diagnostic and therapeutic possibilities. The ability of radiolabeled monoclonal antibodies to localize tumors, markedly contributed to the development of a new intraoperative approach termed "Radioimmunoguided Surgery". This system, being used to better define tumor margin resection as well as occult tumor sites, is of importance in postoperative decision-making. Optimization of this technique is actually under evaluation at our Institution, especially in combination with Biological Response Modifiers. PMID- 8193283 TI - New and old in prognosis determination. AB - Many factors have been identified for the prediction of prognosis in human breast cancer. In this overview the old and recent available prognostic factors are discussed. The prognostic markers widely used are clinical factors (tumor size, age of the patient, etc.), serum markers (CEA, CA 15-3, MSA, CA 125, TK, MCA), pathological factors (histologic differentiation grade, lymph node status) and steroid receptors. More recently molecular biological studies suggest that amplification and overexpression of some oncogenes may play a role in breast cancer prognosis, such as allele deletions of onco-suppressor genes (p53). DNA ploidy status and proliferation markers (S-phase fraction, Ki67 and TLI) may also be useful as prognostic markers. PMID- 8193284 TI - Cell kinetics in breast cancer. AB - In breast cancer the study of prognostic factors has been well developed during last years and many biologic and biochemical parameters have been analyzed. Cell kinetics parameters demonstrated the capability to select patients with different risk of evolution of the neoplasia and in some cases treatment protocols are established by means of proliferation rate. The present study deals with the determination of Thymidine Labelling Index in breast tumors mostly T1-T2 with negative lymph nodes. Results demonstrated that the proliferative activity is higher in younger patients, in T2 cancers compared to T1, and in ductal infiltrating forms compared to the other more frequent histotypes. A significant correlation has been observed between TLI and nuclear grade. The preliminary analysis of the prognostic value of TLI has been two performed using an experimental cut off that is able to discriminate groups of patients with overall survival rate of 67% and 88%, depending on the different proliferative activity of the tumor. PMID- 8193285 TI - Breast cancer heterogeneity assessed by flow cytometry. AB - The natural history of breast cancer is characterized by a marked heterogeneity within and between patients. During the clinical phase, there is ample opportunity for clonal mutation and evolution, and it seems probable that almost all breast cancer patients have multiple tumor clones, each with its own growth requirements, growth rate, ability to metastasize and sensitivity to drugs. Flow cytometry (FCM) is a technique which can rapidly and quantitatively measure a wide variety of cellular features. This can explain its large employment in the development and validation of tumor markers for prognostic and therapeutic purposes. The study of DNA content and cell cycle represents the most common application of FCM on solid tumor analysis. The use of monoclonal antibodies raised against functional and phenotypic cell markers can improve the suitability of FCM to assess the prognostic significance of these parameters; at the same time it could provide a helpful tool for a combined investigation of differentiation, proliferation and aggressiveness tumor markers, and their clinical relevance. PMID- 8193286 TI - Proliferative activity in normal colon mucosa and tumor tissue: clinical implications. AB - The study deals with the analysis of proliferative activity in colon carcinomas and adjacent normal appearing mucosa, evaluated with in vitro 3H-Thymidine and autoradiography. In the colonic mucosa no significant differences in 3H-Thymidine Labelling Index (TLI) were observed in relation to the distance of the sample from the neoplasia. The distribution of S-phase cells along the crypt length is low at the bottom, increases rapidly with a maximum within the lower 25% and decreases in the highest positions. When the proliferative activity is increased there is the possibility of expanding the proliferative compartment towards the luminal region of the crypt. The division of the crypt into 5 parts makes it possible to identify 2 different patterns: the first with a very high TLI in the lower fifth, then a sharp decrease and without labelled cells in the highest parts; the second with labelled cells present also in the luminal fifth. These 2 aspects are characteristic of specimens with the lowest and the highest TLI values respectively. The analysis of TLI in colo-rectal cancers shows that cell kinetics parameters are not related to clinical and histopathological features such as sex, age, Dukes and TNM stages and grade of differentiation. PMID- 8193287 TI - Pharmacological modulation of 5-fluorouracil and its clinical implications: an overview. AB - Authors present an overview of the present knowledge in the field of biochemical modulation of 5-fluorouracil and its potential clinical applications. Interaction between 5-fluorouracil and several modulators, such as leucovorin, interferons, cisplatin, hydroxyurea, thymidine, methotrexate, and PALA are extensively analyzed. PMID- 8193288 TI - Long-term medical management of the renal transplant recipient: a consensus. PMID- 8193289 TI - Steroid-free immunosuppression after renal transplantation. AB - Concerns about the side effects of chronic steroid therapy have prompted increasing interest in steroid-free immunosuppression for renal transplant recipients who are maintained on cyclosporine-based regimens. Studies to date suggest that at least 50% of cyclosporine-treated patients can be managed without steroid therapy. Reported benefits of avoiding or withdrawing steroid therapy have included improvements in hyperlipidemia, hypertension, and glucose intolerance and accelerated growth in children. Whether these effects will increase patient or allograft survival remains to be proved. Furthermore, the benefits of steroid-free immunosuppression must be weighed against the risk of precipitating allograft rejection. Although the elimination of steroids clearly increases the short-term risk of acute rejection, further studies are needed to determine the effects of steroid-free immunosuppression on long-term allograft function and to identify clinical or immunologic factors that can predict a successful outcome after the elimination of steroids. PMID- 8193290 TI - Renal function in patients receiving long-term cyclosporine therapy. AB - The site at which the vasomotor effects of cyclosporine are associated with acute nephrotoxicity appears to be the afferent arteriole. Proposed mechanisms mediating these effects include sympathetic nerve stimulation, disruption of the balance between vasodilating and vasoconstricting prostaglandins, hypersensitivity to vasoactive peptides, and endothelin release. These mechanisms mediate cyclosporine-associated intrarenal vasoconstriction, yet the causal relationship between these changes and the obliterative vasculopathy seen in association with chronic progressive renal allograft dysfunction is uncertain. Histologic findings seen in chronic progressive renal dysfunction are nonspecific and cannot be correlated solely with cyclosporine use. Retrospective studies analyzing both aggregate serial serum creatinine and reciprocal creatinine determinations did not report a pattern of progressive attrition consequent to toxic nephropathy. Prospective studies with serial GFR determinations with various reference substances found no progressive deterioration in allograft function. Both the retrospective and prospective studies indicate that the attrition of renal allograft function associated with cyclosporine use reflect the chronic effects of immunologic injury. Renal function in extrarenal transplant recipients immunosuppressed with cyclosporine can be characterized by an initial decline in native renal function followed by subsequent stabilization beyond the first 6 months. There does not appear to be an inordinate rate of progression to ESRD. PMID- 8193291 TI - Chronic immunosuppression of the renal transplant patient. AB - The advent of potent immunosuppressive drugs to prevent rejection has led to a phenomenal improvement in renal transplant results increasing spectacularly the number of transplant recipients to arrive in the transplant clinic who remain for many years. This has engendered a series of questions about the most appropriate cyclosporine dosing for these patients that prevents rejection while avoiding toxicity. Three separate issues were analyzed: the most appropriate combination strategy with cyclosporine as a base "double" or "triple" therapy; the possibility of conversion from regimens containing cyclosporine to those devoid of it; and the optimal cyclosporine dose for a maintenance regimen. A meta analysis of seven individual prospective and randomized trials of double versus triple therapy encompassing 1,080 patients revealed no statistical difference between the two regimens in terms of graft survival at 1 or 5 yr, patient survival, the rejection rate per patient, or the infection rate. In an analysis of 17 separate studies in which conversion away from cyclosporine was attempted, in 629 individuals with 702 individuals left on cyclosporine as controls, a significant risk of acute rejection (P < 0.001) was found in the withdrawn group without evidence of improved graft survival. Certain factors such as previous rejection, race, and degree of reactivity predicted even more rejection in the withdrawn group. Analyzing six separate studies of renal transplant recipients maintained on cyclosporine for up to 5 yr with renal functional stability, one can conclude that a dose of approximately 4.0 mg/kg per day is optimal. Because of variant pharmacokinetics or concomitant medicines, blood levels can confirm a therapeutic concentration with this target dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193292 TI - Chronic rejection. AB - Current immunosuppressive protocols have significantly decreased graft loss to acute rejection but have had no effect on graft loss to chronic rejection. Recently, attention has been focused on the prevention and management of chronic rejection. Centers must come to a uniform definition of this phenomenon so that studies can be compared. It is believed that the definition should include both a typical clinical course and a definitive biopsy. For kidney transplant recipients, the major risk factor for the development of chronic rejection appears to be a previous acute rejection episode. Other important risk factors include low-dose maintenance immunosuppression and previous infection. Noncompliance probably plays a role in some patients. For extrarenal transplant recipients, chronic rejection has been associated with cytomegalovirus infection and/or HLA-DR matching. Immunoregulatory processes posttransplant may modify or attenuate the development of chronic rejection. Large, prospective clinical studies are required to further elucidate risk factors and to determine the effect of intervention. PMID- 8193293 TI - Hypertension after renal transplantation. AB - Hypertension is a frequent complication after organ transplantation in both children and adults and is a significant risk factor for the development of cardiovascular disease and graft dysfunction. There are multiple mechanisms responsible for the development of posttransplant hypertension. In the precyclosporine era, chronic rejection was the most common cause. The introduction of cyclosporine A has increased the prevalence of hypertension in solid organ transplant recipients. Cyclosporine increases renal vascular resistance by causing vasoconstriction of the afferent arteriole. From a pathophysiologic point of view, a calcium channel blocker should be used as the initial therapy in patients with cyclosporine-associated hypertension. Hypertension needs to be treated aggressively in all transplant recipients in an attempt to minimize allograft and cardiovascular damage. PMID- 8193294 TI - Hyperlipidemia and glucose intolerance in the post-renal transplant patient. AB - This review examines the relationship between renal transplantation and two important metabolic consequences: hyperlipidemia and glucose intolerance. Before cyclosporine, hypertriglyceridemia and hypercholesterolemia were common abnormalities that worsened in the cyclosporine era. In addition to obesity, steroid use, and reduced renal function, cyclosporine plays an independent role in elevating cholesterol levels, with particular reference to the modulation of the low-density lipoprotein receptor. Management includes maintaining low levels of steroid, manipulation of cyclosporine appropriately, diets low in fat and cholesterol, and an exercise program. Pharmacologic management in general revolves around the HMG-COA reductase drugs, which can be used safely if liver function tests and muscle enzymes are monitored. The unmasking of clinically important glucose intolerance occurs in 5 to 10% of patients in the cyclosporine era, not different from the earlier experience. Steroids and cyclosporine independently can worsen glucose tolerance to unmask a genetic predisposition to Type II diabetes in some and to even create glucose intolerance in otherwise normal individuals. Management is based on dietary and immunosuppressive drug dosing manipulations and the judicious use of oral hypoglycemic agents. Half of these recipients may ultimately need insulin. In summary, hyperlipidemia and glucose intolerance remain important metabolic consequences of renal transplantation that affect long-term patient survival unless recognized and treated. PMID- 8193295 TI - The 5'-region of Arabidopsis thaliana cor15a has cis-acting elements that confer cold-, drought- and ABA-regulated gene expression. AB - Previous nuclear run-on experiments indicated that the cor15a (cold-regulated) gene of Arabidopsis thaliana L. (Heyn) has a cold-inducible promoter (Hajela et al., Plant Physiol 93: 1246-1252, 1990). The data presented here indicate that the 5' region of cor15a between nucleotides -305 and +78 (relative to the start of transcription) contains a cis-acting element(s) that can impart cold-regulated gene expression. Histochemical staining experiments indicated that the cor15a promoter is inactive, or very weakly active, in most of the tissues and organs of plants grown at normal temperature and that it becomes activated throughout most of the plant in response to low temperature. Notable exceptions to this general pattern include constitutive activity of the promoter in anthers of control grown plants and apparent inactivity of the promoter in the roots and ovaries of cold treated plants. Histochemical staining experiments also indicated that low temperature regulation of cor15a does not involve the synthesis of a regulatory molecule that can spread throughout the plant and induce cor gene expression at normal growth temperature. Finally, gene fusion experiments indicated that the 5' region of cor15a between nucleotides -305 and +78, in addition to imparting cold regulated gene expression, can impart ABA- and drought-regulated gene expression. PMID- 8193296 TI - The soybean SAUR open reading frame contains a cis element responsible for cycloheximide-induced mRNA accumulation. AB - Little is known about how mRNA stability is regulated in higher plants. The SAURs (Small Auxin-Up RNAs) are a family of highly unstable mRNAs in soybean that rapidly increase in abundance after excised organs are treated with the plant hormone auxin. The SAURs are also induced by protein synthesis inhibitors, including cycloheximide, in the absence of auxin treatment and are superinduced when organs are treated with cycloheximide plus auxin. While the induction of SAURs is transcriptionally regulated by auxin, the induction by cycloheximide is posttranscriptional. Cycloheximide as well as other protein synthesis inhibitors appear to induce SAUR accumulation by increasing the stabilities of these mRNAs. To determine whether the 5'-untranslated region, the 3'-untranslated region, or the open reading frame of these unstable mRNAs is responsible for the cycloheximide inducibility, we have used chimeric genes in transgenic tobacco plants to test each of these mRNA regions. Our results show that the SAUR open reading frame within a chimeric mRNA confers cycloheximide inducibility in transgenic tobacco plants whereas chimeric mRNAs containing the SAUR 5' untranslated region or 3'-untranslated region as isolated elements or in combination are not induced by cycloheximide. These results suggest that the SAUR open reading frame contains sequence elements that are involved in the stability of these mRNAs. PMID- 8193297 TI - Genes encoding acidic and basic class III beta-1,3-glucanases are expressed in tomato plants upon viroid infection. AB - beta-1,3-glucanases are hydrolytic enzymes considered to constitute part of the general array of defense genes induced by pathogen infection in higher plants. We have isolated and characterized two complementary DNA clones, corresponding to new beta-1,3-glucanases from tomato plants (Lycopersicon esculentum) which are expressed upon challenge with citrus exocortis viroid. Amino acid sequence comparison revealed that they are most similar to beta-1,3-glucanases from tobacco, particularly to PR-Q', the unique component of the class III beta-1,3 glucanase. The deduced amino acid sequences of the two tomato beta-1,3-glucanases indicate that, although being highly similar in amino acid sequence, they have different isoelectric points: pI 10.5 for the basic isoform (Tom PR-Q'b) and pI 5.2 for the acidic one (Tom PR-Q'a). The expression of these two beta-1,3 glucanase messenger RNAs (mRNAs) in response to viroid infection and ethephon treatments was examined. mRNAs for these two isoforms are coordinately expressed and induced similarly to mRNAs for other PR proteins, indicating that they are part of a general and coordinate mechanism of response of tomato plants susceptible to viroid infection. PMID- 8193298 TI - Isolation and characterization of a cDNA from flowers of Cynara cardunculus encoding cyprosin (an aspartic proteinase) and its use to study the organ specific expression of cyprosin. AB - Poly(A)+ RNA isolated from flower buds of Cynara cardunculus has been used to prepare a cDNA library. Screening of the cDNA after expression of cloned DNA with antibodies raised against the large subunit of cyprosin 3 resulted in the isolation of six positive clones. One of these clones (cypro1s; a 1.7 kb Eco RI fragment) codes for cyprosin. The nucleotide sequence contain a 1419 bp open reading frame coding for 473 amino acids (aa) including a putative full-length mature protein (440 aa) and a partial prosequence (33 aa). Cypro1s contains a 162 bp 3' non-coding region followed by a poly(A) tail. The deduced amino acid sequence shows high homology to other plant aspartic proteinases. The homology to mammalian and microbial aspartic proteinases is somewhat lower. Plant aspartic proteinases contain an insert of around 100 aa. We are modelling where this plant specific insert will appear in the structure of cyprosin. Using cypro1s as a probe in northern blot analysis, the expression of cyprosin in developing flowers and other tissues has been studied. The signal on the northern blot increased for RNA samples from early (flower buds 6 mm in length) to later stages of floral development (flower buds up to 40 mm in length). In late stages of floral development (open flowers 50 mm in length and styles from such flowers) no hybridization signal was visualized showing that the synthesis of mRNA encoding the cyprosin starts in early stages of floral development and switches off at maturation of the flower.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193300 TI - Differential expression of two calmodulin genes in response to physical and chemical stimuli. AB - Two different calmodulin (CaM) cDNAs (MBCaM-1 and MBCaM-2) were isolated from a vigna radiata lambda gt11 library by screening with a heterologous Arabidopsis cDNA probe (TCH-1). Both cDNAs are 85% homologous inside the coding region but are highly divergent outside this region. The polypeptides encoded by MBCaM-1 and MBCaM-2 are identical except for two conservative substitutions at positions 7 and 10. Southern analysis revealed that both cDNAs are encoded by different genes. Expression studies revealed different patterns of expression of both genes. MBCaM-1 mRNA exhibited a dramatic transient increase in response to touch, while MBCaM-2 expression showed a steady but small increase as compared to MBCaM 1. When plants were grown in complete darkness MBCaM-1 was undetectable and MBCaM 2 exhibited very low levels of expression. One hour after exposure of etiolated seedlings to light MBCaM-1 showed no change, while MBCaM-2 expression was increased. After a 6 h exposure to light there was an induction of both MBCaM-1 and MBCaM-2; however, the magnitude of this increase was much greater for MBCaM 2. When plants were grown under a 16 h light/8 h dark cycle the mRNA levels for MBCaM-1 were lower during the light period and increased during the beginning of the night cycle, while MBCaM-2 showed no change. Plants treated with indole-3 acetic acid had a peak in MBCaM-1 expression 6 h after treatment initiation with a slight decline 3 h after the peak, while MBCaM-2 showed a steady but small increase over time as compared to MBCaM-1. When plants were subjected to salt stress they showed an increase in MBCaM-1 expression 2 h after treatment initiation reaching a maximum after 4 h with no further increase after 6 h, while MBCaM-2 remained unchanged over the time course. PMID- 8193299 TI - Cloning and molecular analysis of structural genes involved in flavonoid and stilbene biosynthesis in grape (Vitis vinifera L.). AB - Genes involved in flavonoid and stilbene biosynthesis were isolated from grape (Vitis vinifera L.). Clones coding for phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), dihydroflavonol 4-reductase (DFR), leucoanthocyanidin dioxygenase (LDOX) and UDP glucose:flavonoid 3-O-glucosyl transferase (UFGT), were isolated by screening a cDNA library, obtained from mRNA from seedlings grown in light for 48 h using snapdragon (Antirrhinum majus) and maize heterologous probes. A cDNA clone coding for stilbene synthase (StSy) was isolated by probing the library with a specific oligonucleotide. These clones were sequenced and when the putative products were compared to the published amino acid sequence for corresponding enzymes, the percentages of similarity ranged from 65% (UFGT) to 90% (CHS and PAL). The analysis of the genomic organization and expression of these genes in response to light shows that PAL and StSy genes belong to large multigene families, while the others are present in one to four copies per haploid genome. The steady-state level of mRNAs encoded by the flavonoid biosynthetic genes as determined in young seedlings is coordinately induced by light, except for PAL and StSy, which appear to be constitutively expressed. PMID- 8193301 TI - Isolation of chalcone synthase and chalcone isomerase cDNAs from alfalfa (Medicago sativa L.): highest transcript levels occur in young roots and root tips. AB - Flavonoids are involved in several different interactions between plants and microorganisms. In the Rhizobium-legume symbiosis, they play an important role as inducers of rhizobial nodulation (nod) genes. We have identified from an alfalfa cDNA library four clones for chalcone synthase (CHS) and two clones for chalcone isomerase (CHI); CHS and CHI are key enzymes in flavonoid biosynthesis. In Medicago sp., CHS is encoded by 8-12 genes, and CHI is encoded by 1-2 genes. Here we report the DNA sequence of these clones as well as their relatedness to other legume CHS and CHI clones. In addition, we report on the expression patterns of two CHS gene family members as well as the CHI gene in M. sativa cv. Iroquois. While CHS and CHI transcript levels are high in root tips and entire young roots, they are low in effective nodules elicited by wild-type strains of Rhizobium meliloti and very low in aerial portions of the plant (stems, leaves, flowers). However, wounding the cotyledons results in a rapid increase in transcript levels of both chalcone synthase and chalcone isomerase genes in these organs. PMID- 8193302 TI - Directed disruption of the Chlamydomonas chloroplast psbK gene destabilizes the photosystem II reaction center complex. AB - Using particle gun-mediated chloroplast transformation we have disrupted the psbK gene of Chlamydomonas reinhardtii with an aadA expression cassette that confers resistance to spectinomycin. The transformants are unable to grow photoautotrophically, but they grow normally in acetate-containing medium. They are deficient in photosystem II activity as measured by fluorescence transients and O2 evolution and they accumulate less than 10% of wild-type levels of photosystem II as measured by immunochemical means. Pulse-labeling experiments indicate that the photosystem II complex is synthesized normally in the transformants. These results differ from those obtained previously with similar cyanobacterial psbK mutants that were still capable of photoautotrophic growth (Ikeuchi et al., J. Biol. Chem. 266 (1991) 1111-1115). In C. reinhardtii the psbK product is required for the stable assembly and/or stability of the photosystem II complex and essential for photoautotrophic growth. The data also suggest that the stability requirements of the photosynthetic complexes differ considerably between C. reinhardtii and cyanobacteria. PMID- 8193303 TI - The presence of enhancers adjacent to the Ac promoter increases the abundance of transposase mRNA and alters the timing of Ds excision in Arabidopsis. AB - Two copies of domain B of the CaMV 35S promoter were inserted ca. 300 bp upstream of the transcriptional start site of the Ac transposase gene. Four independent Arabidopsis transformants containing this fusion (35SenhAc::TPase) were made and the abundance of transposase mRNA in each of them was determined. The presence of the enhancers increased the abundance of the transposase mRNA by about 12-fold compared to that found in plants containing an Ac promoter fusion to the transposase gene (Ac::TPase). Hybrid plants carrying 35SenhAc::TPase and a Ds element inserted in a streptomycin phosphotransferase (SPT) gene were constructed and the frequency with which Ds excision occurred in the developing cotyledons was measured. Moreover, the number of progeny of these hybrid plants which inherited an SPT gene activated by Ds excision was studied in individual F2 families. Those derived from 35SenhAc::TPase often contained higher proportions of streptomycin-resistant (strepR) F2 progeny than those derived from Ac::TPase. These high frequencies of strepR seedlings were comparable to those previously detected after activation of Ds by a CaMV 35S promoter fusion to transposase (35S::TPase), but occurred in fewer families. The higher frequency with which this occurred in families derived from 35SenhAc::TPase compared to Ac::TPase suggests that the presence of enhancers adjacent to the native Ac promoter can influence transposase gene expression, and in this case often results in earlier excision of Ds during plant development. PMID- 8193304 TI - A cold-induced gene from Medicago sativa encodes a bimodular protein similar to developmentally regulated proteins. AB - A new cold-regulated (COR) gene, msa CIC, was isolated by differential screening of a cDNA library from cold-acclimated crowns of alfalfa (Medicago sativa L. cv. Apica). Transcripts of msa CIC were not detectable in unacclimated alfalfa and accumulated to higher levels in cold-acclimated plants of the cold-tolerant cv. Apica than in those of the cold-sensitive cv. CUF-101. The DNA sequence analysis of a full-length cDNA clone revealed that msa CIC encodes for a putative protein (MSACIC) of 166 amino acids with distinct proline-rich and hydrophobic domains. Protein sequence comparisons indicated that MSACIC is similar to a group of bimodular proteins that are developmentally regulated in other plant species. PMID- 8193305 TI - Sequence and functional analyses of the rice gene homologous to the maize Vp1. AB - The homologous gene of the maize Vp1 gene was isolated from rice (Oryza sativa). Sequence analysis revealed that the rice Vp1 gene (Osvp1) encodes a protein of 728 amino acids and is interupted by 5 introns at positions identical to those of the maize gene. Osvp1 transcript was detected in developing embryo as early as 10 days after flowering and decreased toward maturity. Osvp1 transcript was also detected in dry as well as imbided mature embryos. The ability of Osvp1 gene product to activate a target gene was shown by transient expression experiments in rice suspension-cultured cell protoplasts using a reporter gene construct carrying the bacterial beta-glucuronidase (GUS) gene fused to the promoter of OsEm gene, the rice homologue of the wheat Em gene. PMID- 8193306 TI - Rps3 and rpl16 genes do not overlap in Oenothera mitochondria: GTG as a potential translation initiation codon in plant mitochondria? AB - Characterization of the Oenothera mitochondrial ribosomal gene cluster rps19-rps3 rpl16 shows the two genes rps3 and rpl16 to be separated by 9 nucleotides. The first codon of rpl16 is a GTG codon for valine and the only potential translational start. This GTG codon is conserved at the same position in maize, Petunia and Marchantia mitochondria, while sequences diverge upstream. These observations suggest that GTG at least at this position may act as translation initiation codon in plant mitochondria. Analysis of RNA editing suggests both genes to code for functional ribosomal proteins in Oenothera mitochondria. A duplication/recombination event at a decanucleotide in the intron of rps3 created a pseudogene missing part of the intron and the 3' exon. PMID- 8193307 TI - A cold-regulated cyanobacterial gene cluster encodes RNA-binding protein and ribosomal protein S21. AB - A cold-regulated gene cluster, rbpA-rpsU, was isolated by differential screening in the cyanobacterium Anabaena variabilis M3. The two genes were co-transcribed as a 900 nt transcript. The level of this transcript was 5-10 times higher in cells grown at 22 degrees C than in those grown at 38 degrees C. The RbpA protein, which was homologous to plant glycine-rich proteins, exhibited a strong affinity to RNA from this cyanobacterium. PMID- 8193308 TI - Molecular cloning of mannose-binding lectins from Clivia miniata. AB - Screening of a cDNA library constructed from total RNA isolated from young developing ovaries of Clivia miniata Regel with the amaryllis lectin cDNA clone resulted in the isolation of four different isolectin clones which clearly differ from each other in their nucleotide sequences and hence also in their deduced amino acid sequences. Apparently the lectin is translated from an mRNA of ca. 800 nucleotides encoding a precursor polypeptide of 163 amino acids. Northern blot analysis of total RNA isolated from different tissues of Clivia miniata has shown that the lectin is expressed in most plant tissues with very high lectin mRNA concentrations in the ovary and the seed endosperm. PMID- 8193309 TI - Recent findings on prolactin transformation by the lactating rat pituitary. PMID- 8193311 TI - Regulation of lactotrope differentiation in neonatal rats by a milk-borne peptide: a review. PMID- 8193310 TI - Prolactin transit through mammary epithelial cells and appearance in milk. AB - In lactating mammary epithelial cells, prolactin (PRL) binds to its receptors, is endocytosed and carried to the milk. In order to study the transit of the hormone and its receptor respectively, the intracellular pathway of PRL and ot two monoclonal antibodies against PRL-receptor (PRL-R), labelled with biotin and colloidal gold, were monitored in incubated fragments of enzymatically dissociated mammary cells of lactating rabbits. PRL was internalised in endosomes and carried to microvesicular bodies, lysosomes, Golgi apparatus and secretory vesicles containing casein micelles. After 60 min of incubation at 37 degrees C, PRL was released in the incubation medium. M110 anti PRL-R was internalised in endosomes and detected mainly in microvesicular bodies during a one hour incubation. In contrast, A917 anti PRL-R also internalised in endosomes and in microvesicular bodies, was carried out to the Golgi apparatus and to the lumen of the acini after 5 min of incubation at 37 degrees C. These results suggest that an intracellular sorting occurs in the presence of the hormone or the different antibodies. The fatty acid composition of the mammary epithelial cell membranes influences the activity of these cells. To examine the effect of this membrane composition on the transit of PRL, the intracellular pathway of the hormone was studied in mammary cells of lactating rats previously fed with lipid deficient diets. Plasma levels of PRL were not modified in rats receiving a deficient diet compared to controls. Labelled PRL was accumulated inside the microvesicular bodies during a one-hour incubation at 37 degrees C. However, PRL was always detectable in milk, suggesting that the intracellular transit of PRL could be slowed down but not inhibited. Possible relationships between endocytosis of PRL and its secretagogue effect are discussed. PMID- 8193312 TI - Metabolic effect of orotic acid in rat L6 myoblasts. AB - Orotic acid (OA) is an intermediate in the pyrimidine pathway. The main source of OA in the human and animal diet is bovine milk and its products. OA significantly inhibited the stimulation of protein synthesis by FCS derived growth factors in L6 myoblasts. An increasing OA concentration (0.001 mM, 0.01 mM, and 0.1 mM) in a medium containing 2% FCS decreased the proliferation of L6 myoblasts (as measured by the number of cells) as well as the incorporation of traced thymidine into cellular DNA after 24 h incubation. This mitoinhibitory effect was accompanied by a significant reduction of ornithine decarboxylase (ODC) activity, an enzyme which is believed to be a valuable index of cell proliferation. A drop in the cytosol spermine level of L6 myoblasts treated with OA also occurred. A simultaneous, significant, compensative increase of S-adenosylmethionine decarboxylase (SAMDC) activity was noted. The addition of putrescine (2 microM), a product of ODC activity, abolished the depressional influence of OA on protein synthesis in L6 myoblasts, thus confirming its interference with the polyamine pathway. Dibutyryl-cAMP (0.05-0.2 mM) or adenine (25 microM) supplementation, regardless of OA concentration, significantly attenuated the mitoinhibitory effect and its inhibitory action on protein synthesis. This may suggest the existence of a purine deficiency in OA-treated myoblasts. These experiments indicate that increasing cellular OA concentration inhibits cell growth probably by disturbances in the chain of early events (synthesis of cyclic purine mononucleotides, and activity of the ODC/polyamine system), normally evoked by growth stimulating factors. PMID- 8193313 TI - Epidermal growth factor in rat milk is dependent on insulin. AB - Epidermal growth factor (EGF) was measured in milk from four groups of rats: untreated diabetic, insulin-treated diabetic, insulin-treated normal and control rats. In the untreated diabetic group the volume of milk, and the concentration of EGF and the total output of EGF were significantly decreased when compared to the control group. In contrast, the total protein concentration in milk from the untreated diabetic rats was similar to the concentration in milk from the control rats. Insulin-treatment of diabetic rats almost completely reversed the decrease in the milk volume and in the concentration of EGF, and thus normalized the total output of EGF. The insulin-treated normal rats which remained euglycemic had a significantly increased concentration of EGF and of total protein without any difference in the volume of milk when compared to the controls. The results indicate that the secretion of EGF from the mammary glands is dependent on insulin and that the decrement in milk-EGF from diabetic rats is selective when compared to the content of protein in milk. PMID- 8193314 TI - Concerning the physiological role of milk-borne transforming growth factor-alpha for the neonate. PMID- 8193315 TI - Studies on milk-borne insulin-like growth factor-1 and 2 (IGF-1 and IGF-2) and epidermal growth factor (EGF) in suckling rats. PMID- 8193316 TI - Egg, placenta, breast and gut. Comparative strategies for feeding the young. PMID- 8193317 TI - [Effect of nerve growth on the selective increase in cell soma dimensions in septal cholinergic neurons of the rat brain under conditions of cultivation]. PMID- 8193318 TI - [Functional activity of blood mononuclear cells during regeneration of bone tissue]. PMID- 8193319 TI - [Inverter mechanisms of the change in the status of the plasma membranes of hepatocytes during induction of microsomal monooxygenases in adult and aged rats]. PMID- 8193320 TI - [Development of adaptation to stress as a result of a course of transcranial electrostimulation]. PMID- 8193321 TI - [Effect of organophosphorus compounds on pulmonary and systemic circulation]. PMID- 8193322 TI - [Main aspects of pathogenesis of hyperglycemic syndrome under extreme conditions (burn trauma and crush syndrome)]. PMID- 8193323 TI - [Spontaneous activity and evoked potentials in the caudal trigeminal nucleus, ventrobasal thalamus and cerebral cortex in rats with neuropathic trigeminal neuralgia]. PMID- 8193324 TI - [Glucose utilization, hexokinase activity and ATP level in erythrocytes in prolonged alcoholic intoxication, in a period of abstinence and during administration of insulin]. PMID- 8193325 TI - [Effect of ten days of aerobic training on energy potential and system of blood supply of the rat skeletal muscles]. PMID- 8193326 TI - [Dynamics of parameters of lipid peroxidation in erythrocytes during treatment of children with acquired severe aplastic anemia]. PMID- 8193327 TI - [Action of ethanol and limontar in the prenatal period of development on lipid peroxidation and enzymes of antioxidant defense in brain tissue and liver of rat progeny]. PMID- 8193328 TI - [Modulation by super-low concentrations of ganglioside GM1 of oxidative burst in murine macrophages and human neutrophils]. PMID- 8193329 TI - [Glucocorticoid-dependent regulation of expression of binding sites for high density lipoproteins in rat hepatocytes]. PMID- 8193330 TI - [Effect of dexamethasone on the expression of high-density lipoprotein binding sites in a culture of rat hepatocytes (independence of hormone effect from intracellular cholesterol pool)]. PMID- 8193331 TI - [Interaction of multiply-modified (desialated) low-density lipoproteins, isolated from the blood of patients with atherosclerosis,with cellular receptors]. PMID- 8193332 TI - [Action of various analogs of the peptide DSIP on sleep in rats during intragastric infusion]. PMID- 8193333 TI - [Effect of the membrane stabilizer ajmaline and the local anesthetic trimecaine on the pharmacologic effects of strophanthin in experiments in vivo and in vitro]. PMID- 8193334 TI - [Effect of short-term elaboration of a local alimentary instrumental reflex on the protein content in hippocampal neurons]. PMID- 8193335 TI - ["Family" factor and microbiocenosis of healthy human intestine]. PMID- 8193336 TI - [Inhibition of interleukin-2-dependent proliferation of human lymphocytes and expression of interleukin-2 receptors by synthetic peptides--fragments of alpha-2 interferon]. PMID- 8193337 TI - [Isolation and characterization of endometrial leukocyte populations using flow cytometry]. PMID- 8193338 TI - [Suppression of mitogen-stimulated proliferation of human lymphocytes in vitro by synthetic peptides--fragments of alpha-2 interferon]. PMID- 8193339 TI - [Effect of a graft extract for eyelid plasty of the Alloplant(TM) series on DNA synthesis in cell culture]. PMID- 8193340 TI - [Determination of the biological activity of chalone-containing preparation of Ehrlich ascites carcinoma and its fractions, prepared using high performance liquid chromatography, in a culture of cells of this tumor]. PMID- 8193341 TI - [Intracellular ceruloplasmin-like proteins in mammals]. PMID- 8193342 TI - [Conservative fractions of repetitive sequences of the human and mammalian genomes in health, in pathology and prolonged exposure to mutagen]. PMID- 8193343 TI - [Individual differences in reactions to acute stress, related to behavior type (prediction of resistance to stress)]. PMID- 8193344 TI - [Role of various types of adrenoreceptors of the lateral hypothalamus in the mechanisms of formation of natural alimentary motivational excitation]. PMID- 8193345 TI - [Cellular mechanisms of hypertrophic cardiomyopathy in rats with spontaneous hypertension (SHR)]. PMID- 8193346 TI - [Ultrastructural stereologic analysis of rats cardiomyocytes in general overheating]. PMID- 8193347 TI - Pulmonary fat embolism: a distinct cause of severe acute chest syndrome in sickle cell anemia. AB - The etiology of most cases of acute chest syndrome (ACS) in sickle cell disease (SCD) is unknown. Although pulmonary fat embolism (PFE) is frequently found on autopsy, it is rarely considered in the differential diagnosis in pediatric patients. We conducted a study to determine if we could identify PFE in SCD patients with ACS, define the clinical and laboratory course of PFE, and determine if bronchoalveolar lavage is safe and useful in diagnosis of PFE. Twenty-seven SCD patients with ACS were evaluated and compared with 43 control patients. Serial tests (complete blood count, platelet count, nucleated red blood cells [NRBCs], chest x-ray, and oxygen saturations) were compared with steady state results. Diagnosis of PFE was made by quantitative evaluation of pulmonary macrophages for intracellular fat. No serious complications from bronchoscopy were observed. In the SCD patients with ACS, 12 were PFE+ and 15 were PFE-. The clinical course of the two groups was quite different. All PFE+ patients experienced bone pain and 11 of 12 had chest pain. In contrast, only 6 of 15 of PFE- patients had bone or chest pain. Neurologic symptoms developed in 6 of 12 of the PFE+ group and in none of the PFE- group. Mean hospital days for PFE+ was 13 compared with 7 for PFE-. Laboratory studies in PFE+ showed a significant decrease in hemoglobin (-2 g, P < .05), platelet count (-293,000, P < .001), and an increase in NRBCs/100 white blood cells (+8.3, P < .001) compared with PFE-. These results indicate that when PFE is associated with ACS, it is characterized by a distinct clinical course, and that bronchial lavage is a safe and useful test in diagnosing PFE in patients with ACS. PMID- 8193348 TI - Direct interaction of proteoglycan macrophage colony-stimulating factor and basic fibroblast growth factor. AB - The proteoglycan form of macrophage colony-stimulating factor (PG-M-CSF), but not M-CSF with a molecular weight of 85 kD (85-kD M-CSF), bound to immobilized basic fibroblast growth factor (bFGF), and, conversely, bFGF bound to immobilized PG-M CSF, but not to the 85-kD M-CSF. PG-M-CSF has an additional amino acid sequence at its carboxyl terminus (part of a precursor sequence that is removed in 85-kD M CSF by proteolytic processing) and it has one or two chondroitin sulfate glycosaminoglycan chains at the carboxyl terminus. Enzymatic removal of the chondroitin sulfate chain from PG-M-CSF had no effect on the binding between PG-M CSF and bFGF. Ligand blotting analysis with radioiodinated bFGF showed that bFGF specifically bound to the polypeptide that corresponded to the carboxyl terminus of PG-M-CSF and was produced in Escherichia coli transfected with its gene. The exogeneous addition of heparan sulfate, which has strong affinity for bFGF, efficiently inhibited the binding between PG-M-CSF and bFGF. These results show that PG-M-CSF binds bFGF through its carboxyl terminal peptide and that the binding sites for PG-M-CSF and heparan sulfate on bFGF are located close together. PG-M-CSF also significantly reduced the mitogenic action of bFGF on Balb/c 3T3 mouse fibroblastic cells. Therefore, we conclude that PG-M-CSF not only binds bFGF, but also neutralizes the activity of the growth factor. PMID- 8193349 TI - Blood coagulation factor Va abnormality associated with resistance to activated protein C in venous thrombophilia. AB - A coagulation test abnormality, termed activated protein C (APC) resistance, involving poor anticoagulant response to APC is currently the most common laboratory finding among venous thrombophilic patients. Because the anticoagulant activity of APC involves inactivation of factors Va and VIIIa, studies were made to assess the presence of abnormal factors V or VIII. Diluted aliquots of plasma from two unrelated patients with APC resistance and thrombosis were added to either factor VIII-deficient or factor V-deficient plasma and APC resistance assays were performed. The results suggested that patients' factor V but not factor VIII rendered the substrate plasma APC resistant. When factor V that had been partially purified from normal or APC resistant patients' plasmas using immunoaffinity chromatography was added to factor V-deficient plasma, APC resistance assays showed that patients' factor V or factor Va, but not normal factor V, rendered the substrate plasma resistant to APC. Studies of the inactivation of each partially purified thrombin-activated factor Va by APC suggested that half of the patients' factor Va was resistant to APC. These results support the hypothesis that the APC resistance of some venous thrombophilic plasmas is caused by abnormal factor Va. PMID- 8193350 TI - Characterization of genomic PIG-A gene: a gene for glycosylphosphatidylinositol anchor biosynthesis and paroxysmal nocturnal hemoglobinuria. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia characterized by the presence of abnormal subpopulations of blood cells that are deficient in surface expression of glycosylphosphatidylinositol (GPI)-anchored proteins. Recent studies showed that the gene termed PIG-A, which participates in the first step of GPI-anchor biosynthesis, is mutated in the abnormal blood cells from patients with PNH. In this study the genomic PIG-A gene was cloned and characterized to obtain nucleotide sequence information for analyzing somatic mutations of PIG-A in patients with PNH. The PIG-A gene is at least 17 kb long and has six exons. The exon-intron boundaries and 583 bp of the 5' flanking region were sequenced. The 5' flanking region has no TATA-like sequence, but includes four CAAT boxes, two AP-2 sequences, and a CRE sequence, some of which are present in regions necessary for the promoter activity. We report pairs of oligonucleotide primers for polymerase chain reaction that should be useful to amplify and analyze various regions of the PIG-A gene in patients with PNH. PMID- 8193351 TI - Amifostine (WR-2721) shortens the engraftment period of 4 hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support. AB - 4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4 HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4 HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty-three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high-dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy. PMID- 8193352 TI - Molecular cloning of a novel receptor tyrosine kinase gene, STK, derived from enriched hematopoietic stem cells. AB - To identify the novel receptor tyrosine kinases (RTKs) critical to the proliferation of hematopoietic stem cells, we performed polymerase chain reaction based cloning from highly purified murine hematopoietic stem cells. Lineage marker-negative, c-KIT-positive, and Ly6A/E- or Sca-1-positive (Lin-c-KIT+Sca-1+) cells were sorted by a fluorescence-activated cell sorter. Two sets of degenerate oligonucleotide primers were directed to the conserved sequences of the catalytic domain, and were used to amplify cDNAs that encode protein tyrosine kinases (PTKs). One hundred cDNA clones were sequenced and 8 RTKs were identified, as well as 12 non-RTKs and 2 serine/threonine kinases. Sixteen cDNAs were identical to the known kinase genes (PKC beta, JAK-1, JAK-2, TYK-2, HCK, FGR, FYN, BLK, c FES, FER, c-ABL, c-KIT, FLK-1, FLK-2, IGF1R, and ECK). Six novel cDNA sequences (stk series) were identified. However, three of them turned out to be BPK, RYK, and TEK. The remaining three showed high homology to S6 kinase II, JAK-2, and v SEA/c-MET, respectively. Characterization of full-length cDNA sequence of the v SEA/cMET-related gene showed that this was a novel RTK gene and we named this gene STK (stem cell-derived tyrosine kinase). We identified two distinct forms of STK cDNA; the short one encoded a putative truncated protein that lacked most of the extracellular domain. STK was expressed at various stages of hematopoietic cells, including stem cells, but we could not detect any apparent expression in other adult tissues. The expression of the truncated form of mRNA was more predominant than that of the complete form. STK was assigned by fluorescent in situ hybridization to the R-positive F1 band of chromosome 9, the same region to which hepatic growth factor-like protein has been assigned. Characterization of these PTKs, including STK, will be helpful to elucidate the molecular mechanism of the growth regulation of hematopoietic stem cells. PMID- 8193353 TI - Number and location of AUUUA motifs: role in regulating transiently expressed RNAs. AB - Many RNAs coding for either cytokines or oncogenes are unstable and have a short half-life (t1/2). The AUUUA motif is a highly conserved sequence and is repeated three or more times in the 3' untranslated region (3'UTR) of RNAs encoding many of these short-lived cytokines and oncogenes. These sequences can confer instability. In this study, we investigated the role of number and location of AUUUA motifs in stabilization of RNA. We introduced 1xATTTA, 2xATTTA, ATTTTTTTA (second adenosine of 2xATTTA was substituted with a thymidine), 3xATTTA, 5xATTTA, 7xATTTA [AT-rich sequence from granulocyte-macrophage colony-stimulating factor [GM-CSF] gene (AT-62)], and GC-62 (GC sequences were substituted for ATTTA sequences in the 7xATTTA) into the 3'UTR of rabbit beta-globin (R beta G) gene. This construct also contained the neomycin-resistance gene. These expression vectors were transfected into human lung fibroblasts (W138), which constitutively expressed low levels of GM-CSF mRNA. Stable transfectants were selected by growth in G418. Northern blot analysis of actinomycin D-treated, stably transfected cells demonstrated that the number of AUUUA sequences correlated with rapidity of turnover of the chimeric R beta G mRNA. The rank order of stability was GC-62 = 1xATTTA = 2xATTTA (no RNA decay at 4 hours) > 3xATTTA = 5xATTTA (t1/2, 4 hours) > 7xATTTA (t1/2, 2 hours). Stability of mRNA of R beta G also was reduced (t1/2, 2 to 4 hours) when AT-62 was introduced into the second exon of R beta G gene. In these same cells, the t1/2 of GM-CSF RNA was approximately 10 to 15 minutes, suggesting that the AUUUA motifs cannot alone account for the rapid degradation of this cytokine mRNA. Phorbol diesters, including 12-0-tetradecanoyl phorbol 13 acetate (TPA), stabilize a variety of transiently expressed RNAs, including GM CSF RNA. We found that TPA markedly increased (> 30-fold) the accumulation of GM CSF RNA. In contrast, TPA was unable to stimulate the levels of the chimeric R beta G when either 1x, 2x, 3x, or 5xATTTA motifs were fused to 3'UTR, or when either AT-62 or GC-62 control sequences were fused to the second exon. The chimeric beta-globin construct with either AT-62 or ATTTTTTTA in the 3'UTR had only an approximately twofold to threefold increase in accumulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8193354 TI - Molecular cloning of two isoforms of the murine homolog of the myeloid CD33 antigen. AB - CD33 monoclonal antibodies recognize a 67-kD glycoprotein of unknown function that is expressed by early myeloid progenitors and their leukemic counterparts. We report here the cloning of the murine homolog of the human CD33 antigen. Two cDNA clones, differing by an 83-nucleotide insertion in the cytoplasmic region, were isolated. The insertion generated a shift in the reading frame within the cytoplasmic tail, resulting in two mouse CD33 isoforms, m33-A and m33-B, with distinct cytoplasmic domains and with predicted protein core molecular weights of 37 kD and 45 kD, respectively. The cDNAs and deduced amino acid sequences show extensive similarity with the human CD33 sequence with the highest homology occurring in the first and second lg-like domains (61% amino acid identity). The most significant divergence between the human and murine proteins occurs in their cytoplasmic portions. The murine CD33 mRNAs were detected in bone marrow, spleen, thymus, brain, liver, the multipotential progenitor cell line, A4, the myelomonocytic cell line, WEHI3B, the myeloid cell line, M1, and the macrophage cell line, P388, by Northern blot analysis. The expression pattern of the murine CD33 homolog suggests that the function of CD33 antigen in hematopoiesis may be conserved between humans and mice. PMID- 8193355 TI - Isolation and characterization of the human interleukin-9 receptor gene. AB - To better understand the regulation of interleukin-9 (IL-9) receptor expression, we have isolated the genomic clone of the human IL-9 receptor based on its sequence homology with a human IL-9 receptor cDNA isolated from the human megakaryocyte cell line UT-7. The entire genomic structure has been determined. The human IL-9 receptor gene consists of 10 exons spread over approximately 13.7 kb of DNA. The nucleotide sequence of the coding region from the genomic DNA is identical to our cDNA clone. Several blocks of transcriptional control sequence have been identified at the 5' noncoding region of the IL-9 receptor gene that may play an important role in the regulation of the IL-9 receptor gene. A fusion gene containing 659 bp of human IL-9 receptor 5' noncoding region linked to the firefly luciferase gene directed expression of luciferase activity in human embryonic kidney 293 cell line, but not in the mouse fibroblast cell line NIH3T3 cells. PMID- 8193356 TI - Relative antithrombotic effects of monoclonal antibodies targeting different platelet glycoprotein-adhesive molecule interactions in nonhuman primates. AB - The relative antithrombotic effectiveness of targeting glycoprotein (GP) Ib dependent versus GPIIb-IIIa-dependent platelet interactions has been determined in baboons by measuring thrombus formation after infusing comparable antihemostatic doses of anti-von Willebrand factor (vWF) monoclonal antibody (MoAb) BB3-BD5, anti-GPIb MoAb AP1, and anti-GPIIb-IIIa MoAb LJ-CP8 under conditions of arterial and venous flow (shear rates of 750 to 1,000 seconds-1 and 100 seconds-1, respectively). Thrombus formation was quantified as 111In-platelet deposition and 125I-fibrin accumulation on segments of collagen-coated tubing interposed in chronic exteriorized arteriovenous (AV) shunts for 40 minutes. In vitro, anti-vWF MoAb BB3 BD5 (IgG) and anti-GPIb MoAb AP1 [IgG or F(ab)2 fragments] inhibited ristocetin-induced platelet aggregation (IC50 50 nmol/L and 1 mumol/L, respectively), but neither of these MoAbs blocked platelet aggregation induced by adenosine diphosphate (ADP) (P > .5). Conversely, anti-GPIIb-IIIa MoAb LJ-CP8 inhibited platelet aggregation induced by ADP (IC50 1 mumol/L, but failed to block ristocetin-induced platelet aggregation (P > .5). In vivo, the intravenous infusion of anti-vWF MoAb BB3 BD5 or anti-GPIIb-IIIa MoAb LJ-CP8 into baboons at doses that abolished corresponding agonist-induced aggregation ex vivo (bolus injections of 0.5 mg/kg and 10 mg/kg, respectively) prolonged template bleeding times from baseline values of 4.0 +/- 0.3 minutes to > 27 +/- 4 minutes, and to > 26 +/- 4 minutes, respectively (P < .001 in both cases), without affecting the peripheral platelet count (P > .5). However, injection of anti-GPIb MoAb AP1 [10 mg/kg as IgG or 1 mg/kg as F(ab)2 fragments] produced immediate irreversible thrombocytopenia (< 40,000 platelets/microL). Anti-GPIIb-IIIa MoAb LJ-CP8 abolished platelet deposition and fibrin accumulation on collagen segments under both arterial and venous flow conditions (P < .01 in all cases), whereas MoAb BB3 BD5 produced minimal inhibition of platelet deposition and no decrease in fibrin accumulation at arterial shear rates and undetectable antithrombotic outcomes at low shear. Thus, inhibiting GPIIb-IIIa-dependent platelet recruitment abrogates both thrombus formation and platelet hemostatic function at both venous and arterial shear rates. By contrast, interfering with GPIb-vWF-dependent platelet interactions abolishes platelet hemostatic function without producing corresponding antithrombotic effects. PMID- 8193357 TI - von Willebrand disease in the RIIIS/J mouse is caused by a defect outside of the von Willebrand factor gene. AB - An animal model for human type I von Willebrand disease (vWD) has been previously described in the inbred mouse strain RIIIS/J. Murine vWD is characterized by a prolonged bleeding time, normal von Willebrand factor (vWF) multimer distribution, autosomal dominant inheritance, and proportionately decreased plasma vWF antigen, ristocetin cofactor, and factor VIII (FVIII) activities. To study the molecular genetics of murine vWD, a portion of the vWF gene surrounding exon 28 was cloned, sequenced, and used to develop two informative DNA sequence polymorphisms for rapid genotyping by DNA polymerase chain reaction. RIIIS/J mice were crossed with PWK/Ph mice, an inbred line of Mus musculus musculus, and the F1 progeny backcrossed to the parental PWK/Ph strain. vWF antigen levels in F1 mice were not significantly different from the parental RIIIS/J strain but were markedly decreased compared with the parental PWK/Ph mice. Genetic linkage analysis of 104 backcross progeny showed no correlation between vWF antigen level and vWF genotype. These data indicate that murine vWD is caused by a defect at a novel genetic locus, distinct from the murine vWF gene. The distribution of vWF antigen levels among backcross progeny suggests the presence of one major dominant vWD gene in the RIIIS/J mouse with possible modifying contributions from one or more additional minor loci. These observations may provide new insights into the molecular basis and variable expressivity of human vWD. PMID- 8193358 TI - Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4. AB - Heparin-induced thrombocytopenia (HIT) is an important complication of heparin therapy. Although there is general agreement that platelet activation in vitro by the HIT IgG is mediated by the platelet Fc receptor, the interaction among the antibody, heparin, and platelet membrane components is uncertain and debated. In this report, we describe studies designed to address these interactions. We found, as others have noted, that a variety of other sulfated polysaccharides could substitute for heparin in the reaction. Using polysaccharides selected for both size and charge, we found that reactivity depended on two independent factors: a certain minimum degree of sulfation per saccharide unit and a certain minimum size. Hence, highly sulfated but small (< 1,000 daltons) polysaccharides were not reactive nor were large but poorly sulfated polysaccharides. The ability of HIT IgG to recognize heparin by itself was tested by Ouchterlony gel diffusion, ammonium sulfate and polyethylene glycol precipitation, and equilibrium dialysis. No technique demonstrated reactivity. However, when platelet releasate was added to heparin and HIT IgG, a 50-fold increase in binding of radio-labeled heparin to HIT IgG was observed. The releasate was then depleted of proteins capable of binding to heparin by immunoaffinity chromatography. Only platelet factor 4-immunodepleted releasate lost its reactivity with HIT IgG and heparin. Finally, to determine whether the reaction occurred on the surface of platelets or in the fluid phase, washed platelets were incubated with HIT IgG or heparin and after a wash step, heparin or HIT IgG was added, respectively. Reactivity was only noted when platelets were preincubated with heparin. Consistent with these observations was the demonstration of the presence of PF4 on platelets using flow cytometry. These studies indicate that heparin and other large, highly sulfated polysaccharides bind to PF4 to form a reactive antigen on the platelet surface. HIT IgG then binds to this complex with activation of platelets through the platelet Fc receptors. PMID- 8193359 TI - Platelet adhesion to collagen and endothelial cell matrix under flow conditions is not dependent on platelet glycoprotein IV. AB - Platelet membrane glycoprotein IV (GPIV) is a cell-surface glycoprotein that has been proposed as a receptor for collagen. Recently, it has been shown that platelets with the Naka-negative phenotype lack GPIV on their surface, whereas donors with this phenotype are healthy and do not suffer from hematologic disorders. In this study, we compared Naka-negative platelets with normal platelets in adhesion to collagen types I, III, IV, and V and the extracellular matrix of endothelial cells (ECM) under static and flow conditions. No differences in platelet adhesion and subsequent aggregate formation on the collagens types I, III, and IV were observed under static and flow conditions. Adhesion of both homozygous and heterozygous Naka-negative platelets to collagen type V was strongly reduced under static conditions. Collagen type V was not adhesive under flow conditions. No difference in platelet adhesion to ECM was observed, which suggests that GPIV is not important in adhesion to subendothelium, for which ECM may serve as a model. These results indicate that GPIV is not a functional receptor for collagen under flow conditions. PMID- 8193360 TI - Enhanced production of nitric oxide by bone marrow cells and increased sensitivity to macrophage colony-stimulating factor (CSF) and granulocyte macrophage CSF after benzene treatment of mice. AB - Nitric oxide is a short-lived reactive mediator that inhibits bone marrow (BM) cell proliferation induced by granulocyte-macrophage colony-stimulating factor (GM-CSF). The present studies show that nitric oxide also inhibits macrophage colony-stimulating factor (M-CSF)-induced growth of mouse BM cells, an effect that was dependent on the presence of an inflammatory mediator and blocked by the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMA). Treatment of mice with the hematotoxicant benzene (800 mg/kg, intraperitoneally, two times per day, for 2 days) resulted in a significant increase in nitric oxide production by BM cells stimulated with lipopolysaccharide (LPS) and interferon gamma alone or in combination with M-CSF or GM-CSF. Cells from benzene-treated mice also displayed increased sensitivity to the growth-promoting effects of M-CSF and GM CSF. These results suggest that benzene treatment of mice primes BM cells to inducers of nitric oxide. Northern blot analysis showed that this was, at least in part, caused by increased expression of mRNA for inducible nitric oxide synthase (iNOS). Surprisingly, treatment of mice with L-NMA was found to cause a depression in BM cell proliferation and to potentiate benzene-induced decreases in BM cellularity and increases in nitric oxide production. L-NMA administration also augmented nitric oxide production by BM cells. These data indicate that L NMA is hematotoxic and suggest that it may have actions distinct from inhibition of nitric oxide synthase in the BM. PMID- 8193361 TI - Hematopoietic growth factor expression and ATRA sensitivity in acute promyelocytic blast cells. AB - Acute promyelocytic leukemia (APL) is a homogeneous subgroup of acute myeloid leukemias (AMLs) characterized by the presence of the t(15,17) translocation and the resulting promyelocytic myeloid leukemia/retinoic acid receptor alpha (PML/RAR alpha) fusion proteins. To date APL is the only AML that is sufficiently sensitive to all-trans retinoic acid's (ATRA) differentiating effect. In vivo ATRA alone achieves complete remission in most APL patients. However, failure or partial responses are observed and the molecular basis of the absence of ATRA response in these patients has not been determined. To gain insights in the cell growth and differentiation of APL cells, expression of hematopoietic growth factors (HGF) shown to be produced by leukemic cells (interleukin-1 beta [IL-1 beta], IL-6, tumor necrosis factor alpha (TNF alpha), granulocyte colony stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM CSF], and IL-3) was studied in 16 APL samples. Twelve APL cases expressed IL-1 beta, IL-6, and TNF alpha, but not G-CSF, GM-CSF, and IL-3. These cases achieved complete remission with ATRA therapy. The four remaining patients (either TNF alpha negative or G-CSF, GM-CSF or IL-3 positive) did not achieve complete remission with ATRA. In all cases, in vivo response to ATRA therapy was correlated to the in vitro differentiation effect of all-trans retinoic acid 10( 6) mol/L. Thus, ATRA differentiation induction was strongly correlated to the HGF expression (P < .0001). These results suggest that the presence or absence of HGF's expression by APL cells may contribute to the therapeutic effect of ATRA in this disease. PMID- 8193362 TI - Heteroduplex analysis of T-cell receptor gamma gene rearrangements for diagnosis and monitoring of cutaneous T-cell lymphomas. AB - The possibility to detect markers of T-cell clonality at the T-cell receptor (TCR) beta and gamma loci in skin biopsy samples has proven to be helpful for the often difficult clinical and immunohistochemical diagnosis of cutaneous T-cell lymphoma (CTCL). However, particularly at the early stage of the neoplastic infiltration, an emerging clonal pattern at Southern may be obscured by the germline TCR configuration of the predominant dermal and epidermal cell component. Additionally, multiple TCR gamma rearranged bands of variable intensity are often observed, either in the presence or in the absence of a major clone. To overcome these difficulties, we have investigated the T-lymphocyte clonality in selected patients with variable signs of CTCL by means of heteroduplex analysis of the amplified TCR gamma VJ junctions, separated in nondenaturing polyacrylamide gel. This technique has several advantages over standard Southern blot because it is simple, rapid, not radioactive, and likely more sensitive than other polymerase chain reaction-based procedures. In particular, the cases with uncertain or contradictory TCR beta and gamma patterns were solved by the heteroduplex analysis, showing homoduplex or heteroduplex bands of clonal nature. The direct sequence of the VJ junctions, easily obtained from the homoduplex or heteroduplex bands, allowed us to confirm the same clonal marker in two apparently different skin lesions and in different biopsy samples obtained from the same patients, either at the same or different time points, thus emphasizing the utility of this method in monitoring CTCL clinical progression. PMID- 8193363 TI - Idiotypic vaccination against human B-cell lymphoma. Rescue of variable region gene sequences from biopsy material for assembly as single-chain Fv personal vaccines. AB - Idiotypic determinants on neoplastic B cells could provide tumor antigens for vaccination of patients with B-cell tumors. Because this approach requires an individual vaccine for each patient, simple methods for obtaining idiotypic antigen are desirable. Using polymerase chain reaction (PCR) with family-based V gene and J-region primers, the variable region genes of heavy and light chains (VH and VL) of Ig have been obtained from biopsy material from 13 patients with B cell tumors. In each case, analysis of random clones derived from the PCR product showed repeated, clonally-related sequences, whereas normal lymphoid tissue generated no repeated sequences. In 3/3 cases, the repeated sequences were found to be the same as those in a tumor-derived hybridoma. Mutational patterns in the V-genes differed among the tumors, with follicular lymphoma tending to be more highly mutated. The individual VH and VL sequences have been assembled with a flexible linker sequence to encode single-chain Fv (scFv). The scFv sequences can be cloned into bacterial expression vectors to produce protein, or into vectors suitable for direct vaccination using naked DNA. In a model system, expressed scFv protein retained all idiotypic determinants defined by a panel of five anti idiotypic monoclonal antibodies (MoAbs). Similarly, expressed scFv proteins from two patients were shown to react with anti-idiotypic antibodies. This approach allows production of potential vaccines from surgical biopsies within 2 to 3 weeks. PMID- 8193364 TI - Novel retinoic acid, 9-cis retinoic acid, in combination with all-trans retinoic acid is an effective inducer of differentiation of retinoic acid-resistant HL-60 cells. AB - Recent studies have shown that a high proportion of patients with acute promyelocytic leukemia (APL) achieve complete remission after treatment with all trans retinoic acid (RA). Nevertheless, despite an initial good response, most patients that received continuous treatment with all-trans RA relapse and develop RA-resistant disease. The 9-cis RA is a high-affinity ligand for retinoid X receptors (RXRs) and also binds efficiently to retinoic acid receptors (RARs); all-trans RA is a ligand for RARs. Both alone are able to induce differentiation of wild-type HL-60 cells. We found that neither all-trans RA nor 9-cis RA (< 2 x 10(-6) mol/L) induced differentiation of RA-resistant HL-60 cells into either mature granulocytes or monocytes. However, morphologic differentiation of the RA resistant HL-60 cells was induced by 10(-6) mol/L all-trans RA combined with various concentrations (10(-12) to 10(-6) mol/L) of 9-cis RA. Electron microscopic examination also confirmed that the combination of both retinoids induced RA-resistant HL-60 cells to differentiate to mature granulocytes. Functional analysis of differentiation (NBT reduction activity) confirmed the necessity of both analogs to induce differentiation. Also, expression of myeloid specific differentiation antigens (CD11b and CD14) as well as migration inhibitory factor-related protein (MRP)-8/14 mRNAs were upregulated only in the presence of both retinoids in a dose-dependent manner. In these conditions 3H thymidine incorporation was inhibited and numbers of viable cells were decreased, suggesting that all-trans RA with 9-cis RA may inhibit cell growth and induce differentiation of RA-resistant HL-60 cells into mature granulocytes. These studies suggest that 9-cis RA in combination with all-trans RA is an effective inducer of RA-resistant HL-60 cells and may have implications for both the biology of retinoids and clinical treatment of RA-resistant acute myelogenous leukemia, including APL patients. PMID- 8193365 TI - Retinoic acid-resistant HL-60 cells exclusively contain mutant retinoic acid receptor-alpha. AB - Sequence analysis of the retinoic acid receptor-alpha (RAR alpha) gene from a subline of HL-60 cells (RA-res) stably resistant to all-trans retinoic acid (RA) disclosed a single-base change in codon number 411, the same C to T transition previously reported in an independently selected HL-60 RA resistant clone by Robertson et al (Blood 80:1885, 1992). This mutation eliminates a FokI restriction endonuclease site. Using primers framing this mutation in exon 9 of the RAR alpha gene, we showed that polymerase chain reaction products amplified from either mRNA or genomic DNA templates from the RA-res subline were completely resistant to FokI digestion whereas those from wild-type (wt) HL-60 cells could be digested to completion. The lack of a normal allele in the RA-res cells was confirmed by mixing experiments and hybridization analyses. Southern blot analysis of DNA from the RA-res and wt cells versus control placental DNA indicated that the RAR alpha gene is not haploid. The independent isolation of the same RAR alpha mutation in different laboratories suggests either that the mutation exits in a small subpopulation in the wt line or that this is a mutational "hot spot." Furthermore, the results indicate that if a dominant negative mode of resistance is involved in the RA-res subline, this must involve interference with the function of heterologous receptor proteins such as the retinoid X receptors. The lack of any normal RAR alpha in this subline may facilitate studies of the mode of action of retinoids. PMID- 8193366 TI - Genotypical classification of neutrophil Fc gamma receptor III by polymerase chain reaction-single-strand conformation polymorphism. AB - We classified the genotype of neutrophil Fc gamma receptor III (FcRIII) (CD16) with a new method. Genomic DNA from mononuclear cells of 39 unrelated healthy donors (13 NA1/NA1, 13 NA2/NA2, and 13 NA1/NA2 typed serologically) were subjected to polymerase chain reaction (PCR) to amplify the polymorphic third exon of the FcRIII genes. The PCR products were heat denatured, electrophoresed, and visualized by silver staining. Allelic differences were detected by distinctive electrophoretic patterns of each single strand, depending on their sequence specific conformations (single-strand conformation polymorphism [SSCP]). The genotypes of neutrophil FcRIII determined by this method were consistent with the phenotypes of NA antigens determined by serologic examinations. These results indicate that the PCR-SSCP system is a very useful tool for genotyping of the neutrophil FcRIII. PMID- 8193367 TI - Macrophage colony-stimulating factor-induced bone marrow macrophages do not synthesize or release prostaglandin E2. AB - Previously, we found that murine bone marrow-derived macrophages (MO) induced in vitro by MO-specific colony-stimulating factor (M-CSF) have little capacity to release prostaglandin E2 (PGE2) and other eicosanoids. This work focused on the functional and transcriptional expression of the key enzymes for the PGE2 synthesis in the MO. Nonadherent bone marrow cells were cultured with RPMI1640 plus 10% fetal bovine serum (FBS) further supplemented with either M-CSF or granulocyte-macrophage (GM)-CSF and interleukin-3 (IL-3). Cellular PGG/H synthase (cyclooxygenase) levels were quantified by cytometric analysis with antibodies specific for the two isozymes of PGG/H synthase (PGG/H synthases 1 and 2). The enzyme activity was monitored by adding exogenous arachidonic acid (AA) substrate to the bone marrow MO cultures and to the cell-free particulate fractions. The levels of PGE2 converted were quantitated by radioimmunoassay (RIA). mRNA levels of the enzymes were detected by Northern blot analysis hybridized with mouse PGG/H synthase cDNA probes, 2.7 kb (PGG/H synthase 1) and 4.2 kb (PGG/H synthase 2). In addition, cellular phospholipase A2 (PLA2) activities were detected with sn-2-14C-arachidonyl phosphatidylcholine as a substrate. Cells proliferating in the presence of GM-CSF and IL-3 for more than 4 days showed significant release of PGE2 (> 7 ng/10(6) cells) when stimulated by AA. These cells also expressed significant amounts of PGG/H synthase 1 protein, its mRNA (2.7 kb) and cellular PLA2. M-CSF-induced MO, in sharp contrast, expressed little PGG/H synthase protein, mRNA, cellular enzyme activity, or PGE2 release, despite comparable levels of cellular PLA2 activity. These data suggest that the capacity of differentiating marrow-derived MO to form PGE2 is growth factor-dependent. PMID- 8193368 TI - C3a activates the respiratory burst in human polymorphonuclear neutrophilic leukocytes via pertussis toxin-sensitive G-proteins. AB - In contrast to C5a, which represents a well-established potent activator of the respiratory burst in polymorphonuclear neutrophilic granulocytes (PMN), the functional role of C3a in the activation of PMN is, so far, poorly understood. Herein, the potential role of human C3a in the activation of the respiratory burst in human PMN was investigated. The release of reactive oxygen species (ROS) of PMN from healthy donors was measured by lucigenin-dependent chemiluminescence. C3a dose-dependently induced the production of ROS in human PMN in the range between 10 ng/mL and 1,000 ng/mL, whereas C3a-desArg was inactive. Flow cytometric measurement of H2O2 by dihydrorhodamine-123 labeling of anti-CD16 stained PMN showed that predominantly neutrophilic PMN are responsible for the C3a-induced activation of the respiratory burst. To exclude that C3a stimulation was caused by contamination with C5a, the specificity of C3a-induced activation of PMN was shown using monoclonal antibodies (MoAbs). Accordingly, the effect of C3a was completely abolished in the presence of Fab fragments of a blocking anti C3a MoAb. In addition, blockade of the C5a receptor by the anti-C5a receptor (anti-C5aR) MoAb, S5/1, totally inhibited the C5a-induced production of ROS, whereas the C3a response in the presence of the anti-C5aR MoAb was unaffected. The specificity of the response was further confirmed by homologous desensitization after restimulation with C3a. In contrast, no cross desensitization was observed upon stimulation with C5a. The C3a-induced ROS production by PMN was inhibited by pertussis toxin, indicating the involvement of guanine nucleotide-binding proteins (Gi proteins) in the signal transduction process initiated by C3a. In addition, stimulation of PMN by C3a resulted in a transient increase in the cytosolic free calcium concentration ([Ca2+]i) in a dose-dependent manner. In contrast to C3a-induced ROS production, C3a did not induce a chemotactic response in PMN, indicating functional qualitative differences as compared with C5a. In summary, these results show that C3a is a potent activator of the respiratory burst in human PMN. Therefore, these findings point to a novel role of C3a in the pathogenesis of inflammatory diseases associated with increased C3a levels and PMN activation. PMID- 8193369 TI - Inhibitory cytokine circuits involving transforming growth factor-beta, interferon-gamma, and interleukin-2 in human monocyte activation. AB - We have previously reported that transforming growth factor-beta 1 (TGF-beta 1) inhibits interleukin-6 (IL-6) induction by IL-2 and IL-1 in fresh human monocytes. We investigated the effects of TGF-beta 1 on the expression of tumoricidal activity induced by IL-2 or interferon-gamma (IFN-gamma) in human monocytes. We showed that TGF-beta 1 specifically inhibited, in a dose-dependent manner, IL-2-induced but not IFN-gamma-induced monocyte tumoricidal activity. The inhibitory effects of TGF-beta 1 on IL-2-activated monocytes were not caused by down-modulation of the IL-2 receptor beta (IL-2R beta) because the treatment of monocytes with IL-2 and TGF-beta 1 increased IL-2R beta mRNA expression. However, we found that TGF-beta 1 down-modulated IL-2-induced IL-2R gamma mRNA, which may be responsible for the TGF-beta 1 inhibition of monocyte activation by IL-2. The resistance of the IFN-gamma-induced activation to the inhibitory effects of TGF beta 1 could be caused by the ability of IFN-gamma to decrease TGF-beta 1 receptor expression, as shown by cross-linking experiments. Overall, these results showed that TGF-beta 1 is a powerful inhibitor of IL-2- but not of IFN gamma-induced activation of monocytes to a cytotoxic stage. This differential effect may be attributed to modulation of cytokine receptor expression. PMID- 8193370 TI - Phosphorylation of protein 4.1 in Plasmodium falciparum-infected human red blood cells. AB - The composition of the erythrocyte plasma membrane is extensively modified during the intracellular growth of the malaria parasite Plasmodium falciparum. It has been previously shown that an 80-kD phosphoprotein is associated with the plasma membrane of human red blood cells (RBCs) infected with trophozoite/schizont stage malaria parasites. However, the identity of this 80-kD phosphoprotein is controversial. One line of evidence suggests that this protein is a phosphorylated form of RBC protein 4.1 and that it forms a tight complex with the mature parasite-infected erythrocyte surface antigen. In contrast, evidence from another group indicates that the 80-kD protein is derived from the intracellular malaria parasite. To resolve whether the 80-kD protein is indeed RBC protein 4.1, we made use of RBCs obtained from a patient with homozygous 4.1(-) negative hereditary elliptocytosis. RBCs from this patient are completely devoid of protein 4.1. We report here that this lack of protein 4.1 is correlated with the absence of phosphorylation of the 80-kD protein in parasite-infected RBCs, a finding that provides conclusive evidence that the 80-kD phosphoprotein is indeed protein 4.1. In addition, we also identify and partially characterize a casein kinase that phosphorylates protein 4.1 in P falciparum-infected human RBCs. Based on these results, we suggest that the maturation of malaria parasites in human RBCs is accompanied by the phosphorylation of protein 4.1. This phosphorylation of RBC protein 4.1 may provide a mechanism by which the intracellular malaria parasite alters the mechanical properties of the host plasma membrane and modulates parasite growth and survival in vivo. PMID- 8193371 TI - Mild elliptocytosis associated with the alpha 34 Arg-->Trp mutation in spectrin Genova (alpha I/74). AB - We report a new mutation responsible for nonhemolytic hereditary elliptocytosis (HE). The proband displayed an impaired spectrin self-association and an increase of the alpha I 74-kD fragment (alpha I/74 abnormality). The responsible mutation occurred in exon 2 of spectrin alpha-gene: alpha 34 Arg-->Trp (CGG-->TGG), defining spectrin Genova. In Trans to allele alpha Genova, the proband disclosed allele alpha LELY, a common low-expression allele of spectrin alpha-gene. It was recognized through particular peptide maps as well as characteristic mutations in exon 40 and intron 45, respectively. The father, who carried allele alpha Genova, but not allele alpha LELY, had a milder presentation. The sensitization of allele alpha Genova by allele alpha LELY was noticeable in the proband as compared with his father. Nevertheless, it was not as sharp as that observed with many other alpha I/74 HE alleles. Therefore, each alpha I/74 HE allele has a distinct intrinsic severity. PMID- 8193372 TI - Interaction of rare illegitimate recombination event and a poly A addition site mutation resulting in a severe form of alpha thalassemia. AB - The clinical diversity of thalassemia depends on interaction of diverse genetic defects. We have characterized a severe form of alpha thalassemia caused by coinheritance of a rare alpha-globin gene deletion and a nondeletional defect in a southern Italian family. The proband, a 7-year-old girl, exhibited an abnormal hemoglobin electrophoresis pattern with hemoglobin H and hemoglobin Barts, indicating inheritance of H and hemoglobin Barts, indicating inheritance of a severe form of alpha thalassemia. Southern blot analysis of DNA showed normal as well as aberrant alpha-globin gene fragments indicating heterozygosity for a deletional form of alpha thalassemia in the proband and her mother. The coinheritance of a nondeletional form of alpha thalassemia (alpha alpha T) was suspected because of the severity of the proband's phenotype and the presence of normal alpha-globin gene fragments in the father. Selective polymerase chain reaction of the paternal alpha 1- and alpha 2-globin genes in the proband followed by DNA sequence analysis showed an AATAAA to AATGAA mutation in the polyadenylation signal sequence of the alpha 2-globin gene. Genomic DNA mapping and sequence analysis of a unique polymerase chain reaction product generated across the deletion breakpoint of the maternal allele showed a 5,201-bp deletion extending from 870 nucleotides 5' of the alpha 2-globin gene to nucleotide +519 in the alpha 1-globin gene. This deletion is similar to that previously suggested by blotting studies in a Greek family (Pressley et al, Nucleic Acids Res 8:4889, 1980) and removes the entire alpha 2-globin gene and a portion of the 5' end of the alpha 1-globin gene. Sequence characterization of the resultant aberrant truncated alpha 1-globin gene from the proband showed a 27 nucleotide duplication corresponding to the 3' end of the alpha-globin gene IVS-2 region separated by the insertion of a tetranucleotide (GGTT), suggesting that this deletion is caused by an illegitimate recombination event. PMID- 8193373 TI - Molecular study of eight Japanese cases of glucose-6-phosphate dehydrogenase deficiency by nonradioisotopic single-strand conformation polymorphism analysis. AB - Using a newly developed nonradioisotopic method of polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis combined with the direct sequencing using the fluorescence-labeled terminator, we identified seven missense mutations, 527 A-->G, 1003 G-->A, 1159 C-->T, 1160 G-->A, 1229 G-->A, 1246 G-->A, and 1361 G-->A, in eight Japanese patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Except for the 527 A-->G, each mutation has been reported to cause variants G6PD Chatham, G6PD Guadalajara, G6PD Beverly Hills, G6PD "Japan", G6PD Tokyo, and G6PD Andalus, respectively. In addition, a single base deletion in intron 5 was found in the patients with G6PD Guadalajara or G6PD Andalus. The variant with unique 527 A-->G was characterized and designated as G6PD Shinshu. We also characterized G6PD "Japan" and found that the variant had the striking resemblance with G6PD Riverside, bearing a missense mutation in the same codon, but causing a different amino acid substitution. Our modified PCR SSCP analysis using minigel and ethidium bromide staining could detect six of the eight diverse mutations in the G6PD gene. Because it is easy and requires no special apparatus, this modified method will be useful for screening mutations in the G6PD gene. PMID- 8193374 TI - Glycophorin He(Sta) of the human red blood cell membrane is encoded by a complex hybrid gene resulting from two recombinational events. AB - A complex glycophorin (GP) variant of the human red blood cell membrane exhibiting both He and Sta antigens was characterized at the molecular level. Restriction mapping identified two novel Msp I fragments derived from the 5' and 3' portions of the GPHe(Sta) gene, respectively. Genomic DNA, including exons II V and their splice junctions, was amplified by polymerase chain reaction, and the nucleotide sequences were determined. Comparison with the GPA and GPB sequences showed the presence in GPHe(Sta) of multiple recombinational breakpoints. In the 5' region of the variant gene, a sequence covering a portion of exon II to intron 2 had been transferred from GPA to GPB, resulting in a B-A-B hybrid structure. Such a gene conversion-like event introduced a number of templated and untemplated nucleotide replacements and was the direct cause for the expression of the He antigen. In the 3' region of the variant gene, an unequal crossover from GPB to GPA took place in the third intron at a recombination site apparently identical to that observed in the B-A hybrid GPSta type A gene. These results indicated that GPHe(Sta) occurs as a B-A-B-A hybrid gene, most likely originating from a two-step mechanism of homologous recombination. Transcript analysis showed the maturation from the GPHe(Sta) pre-mRNA of two shortened mRNAs of which the exon III-deleted species encodes both the He and Sta antigens. PMID- 8193375 TI - Relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: the case for giving donor leukocyte transfusions before the onset of hematologic relapse. AB - Fourteen patients with chronic myeloid leukemia (CML) relapsing after allogeneic bone marrow transplant (BMT) were treated with leukocyte transfusions from the original marrow donor (sibling, n = 9; volunteer unrelated, n = 5). The relapse was defined at the molecular level in two cases, cytogenetically in five cases and hematologically in seven cases. Ten patients responded, seven of seven patients with cytogenetic/molecular relapse compared with three of seven with hematologic relapse (P < .03). All five recipients of cells from unrelated donors responded. Eight of the 10 responders have achieved polymerase chain reaction negative status and this persisted in three patients for more than 2 years; no responder has shown sign of relapse. Reversible marrow aplasia occurred in two patients, both treated in hematologic relapse. Severe graft-versus-host disease occurred in four patients and was fatal in one. We confirm previous reports that donor leukocyte transfusions are effective in the management of CML in relapse after BMT. In this series, therapeutic intervention before the onset of hematologic relapse was associated with an increased likelihood of response and no marrow aplasia. PMID- 8193376 TI - Fractionated versus single-dose total body irradiation at low and high dose rates to condition canine littermates for DLA-identical marrow grafts. AB - We explored in dogs the immunosuppressive properties of 450 cGy total body irradiation (TBI) delivered from two opposing 60Co sources, as assessed by the criterion of successful engraftment of allogeneic genotypically DLA-identical littermate marrow. Two questions were asked in this study. Firstly, does dose rate affect the immunosuppressive effect of TBI when administered in a single dose? Secondly, does fractionation alter the immunosuppression of TBI when delivered at a very fast dose rate? Dose rates studied included 7 and 70 cGy/min, and fractionation involved four fractions of 112.5 cGy each, with 6-hour minimum interfraction intervals. Six of 7 dogs receiving 450 cGy single-dose TBI at 70 cGy/min showed sustained engraftment of the allogeneic marrow, compared with 1 of 7 dogs receiving single-dose TBI at 7 cGy/min (P = .01). Fractionated TBI at 70 cGy/min resulted in sustained allogeneic engraftment in 3 of 10 dogs, a result that was statistically significantly worse than that with single-dose TBI at 70 cGy/min (P = .03) and not statistically different (P = .24) from that with fractionated TBI delivered at 7 cGy/min (0 of 5 dogs engrafted). A single dose of 450 cGy of TBI delivered at a rate of 70 cGy/min is significantly more immunosuppressive than the same total dose delivered at 7 cGy/min. Fractionated TBI at 70 cGy/min is significantly less immunosuppressive than single-dose TBI at 70 cGy/min and not significantly different from fractionated TBI administered at 7 cGy/min. Results are consistent with the notion that significant DNA repair in lymphoid cells is possible during interfraction intervals at the relatively high dose rate of 70 cGy/min. PMID- 8193377 TI - Allogeneic T-cell clones able to selectively destroy Philadelphia chromosome bearing (Ph1+) human leukemia lines can also recognize Ph1- cells from the same patient. AB - Immunocompetent cells in bone marrow allografts have been associated with a graft versus-leukemia (GVL) effect. To further characterize effector mechanisms that may be involved in this GVL phenomenon, we have previously established an in vitro model to identify allogeneic T-cell clones that selectively mediate cytotoxicity against a patient's leukemic cells, but not against nonleukemic lymphocytes from the same patient. We have modified this in vitro model to test whether the Ph1 chromosome and the P210 fusion protein it controls have a detectable role in leukemia-specific recognition by allogeneic T-cell clones. In this report, T-cell lines reactive with allogeneic Ph1 chromosome-bearing (Ph1+) chronic myeloid leukemia (CML) cell lines were derived and selected to be minimally reactive with Ph1 negative (Ph1-) lymphoid lines from the same patient. However, after prolonged culture, these same T-cell lines also mediated significant destruction of the Ph1- target cells from the same patients. These T cell lines specifically recognized cells from the allogeneic CML patient to which they were sensitized, and were not contaminated by an outgrowth of natural killer cells. Furthermore, subclones could be derived from these T-cell lines, and some of these subclones again showed selective killing of the allogeneic Ph1+ leukemia cell lines, and not of the Ph1- cell line from the same patient. Analyses of T cell receptor (TCR) genes showed the alloreactive T-cell lines and the Ph1+ selective subclones derived from them to be of the same clonal origin. This suggests that the same T cells reacting with antigens expressed on the nonleukemic Ph1- targets can at times selectively and preferentially kill the allogeneic Ph1+ cells. As the same TCR that recognizes Ph1+ cells also can recognize the Ph1- targets, it appears that the Ph1+ chromosome does not play a detectable role in recognition by these allogeneic T-cell clones. This in vitro observation may provide a model for evaluating the relationship between GVL and graft-versus-host disease effects. PMID- 8193378 TI - Development of a retroviral construct containing a human mutated dihydrofolate reductase cDNA for hematopoietic stem cell transduction. AB - A double-copy Moloney leukemia virus-based retroviral construct containing both the NeoR gene and a mutant human dihydrofolate reductase (DHFR) cDNA (Ser31 mutant) was used to transduce NIH 3T3 and mouse bone marrow (BM) progenitor cells. This resulted in increased resistance of these cells to methotrexate (MTX). The transduced BM progenitor cells were returned to lethally irradiated mice. The recipients transplanted with marrow cells infected with the recombinant virus showed protection from lethal MTX toxicity as compared with mock-infected animals. Evidence for integration of the proviral DNA was obtained by amplification of proviral DNA by polymerase chain reaction (PCR) and Southern analysis. Sequencing a portion of the PCR-amplified human DHFR cDNA showed the presence of the mutation. These studies with the human Ser31 mutant DHFR cDNA gave results comparable with those obtained with the mutant murine DHFR cDNA (Leu to Arg22) in developing MTX-resistant BM. The Ser31 mutant human DHFR cDNA is currently being tested for infection of human CD34+ human BM and peripheral blood stem cells in vitro. PMID- 8193379 TI - Minimal residual disease is more common in patients who have mixed T-cell chimerism after bone marrow transplantation for chronic myelogenous leukemia. AB - Determining both lymphoid chimerism and the presence of minimal residual disease after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) could be helpful to the understanding of the biology of leukemic relapse in this disease. We prospectively investigated 32 patients with CML post BMT by assessing T-cell chimerism and minimal residual disease using sensitive polymerase chain reaction (PCR) methodologies. Patients were studied between 1 and 24 months post-BMT. Thirty patients received a T-cell-depleted marrow grafts and 2 received unmanipulated marrow. All but 1 patient were conditioned with total body irradiation (TBI)+thiotepa+cyclophosphamide (Cy). The other patient received TBI+Cy as conditioning. The T cells were exclusively of donor origin in 12 of 16 patients who were tested at 1 month post-BMT, but were mixed chimeric in 11 of these patients by > or = 3 months. Once mixed T-cell chimerism was documented, no patient returned to having all donor T-cells. At a median follow up of 12 months, minimal residual disease was present in 18 of 22 patients with mixed T-cell chimerism and in 3 of 10 patients with full donor chimerism. The actuarial molecular relapse rate at 24 months for the two groups is 91% and 33%, respectively (P < .02). The finding of BCR-ABL mRNA within the first 6 months of transplant or on two consecutive assays was highly predictive of subsequent cytogenetic or hematologic relapse (P = .032 and P < .02, respectively). Ten patients, 9 with mixed T-cell chimerism, have relapsed (4 clinical, 6 cytogenetic) at a median of 12 months post-BMT. These data suggest that mixed T cell chimerism may be a marker for abrogation of graft-versus-leukemia activity that is thought to be pivotal in eradicating minimal residual disease after BMT for CML. PMID- 8193380 TI - Cyclophosphamide plus ATG conditioning is insufficient for sustained hematopoietic reconstitution in patients with severe aplastic anemia transplanted with marrow from HLA-A, B, DRB matched unrelated donors. PMID- 8193381 TI - Identification of a novel termination codon mutation (TAA-->TAT, Term-->Tyr) in the alpha 2 globin gene of a Laotian girl with hemoglobin H disease. PMID- 8193382 TI - Patient-therapist sexual involvement: a review of clinical and research data. AB - Core concepts and selected research addressing the issue of patient-therapist sexual involvement (PTSI) are examined. Topics covered include the prevalence of PTSI, its suspected causes, the seduction process employed by offending therapists, the factors involved in patient's vulnerability, the mechanisms by which patients are damaged by PTSI, the types of harm caused to patients, the treatment of patients after PTSI, and the prevention of PTSI. The need to expand empirical research in all aspects of PTSI from the patient as well as from the therapists' perspective is strongly emphasized. PMID- 8193383 TI - The mock trial in psychiatric staff education. AB - The mock trial is an important educational technique that has seldom been reported in the medical literature. In this paper we describe the evolution of mock trials as a regular component in the educational program for our multidisciplinary staff. The mock trial is not only an excellent strategy for teaching about the interface between psychiatry and the law, but also for teaching about malpractice, documentation, and medical reasoning. The most effective presentation used an actual case from our facility, practicing attorneys, and an experienced judge in a condensed version of a trial. PMID- 8193384 TI - Patterns of substance abuse and intoxication among murderers. AB - A series of 100 murderers was examined to discern patterns of substance abuse and intoxication in relation to homicidal events. More than half of the study subjects were found to be actively abusing drugs at the time of their crime, and almost half were intoxicated. Alcohol was the drug most often abused. Demographic and other discriminating factors were utilized to examine the hypothesis that murderers do not constitute a homogeneous population and that subgroups differ in their abuse patterns. Cluster analytic techniques were applied to the study population. Utilizing a set of 13 proximate causal factors, a typology of seven distinct homicide profiles was created. Two of the seven profiles exhibited extremely high abuse and intoxication rates, three others intermediate rates, and two profiles very low rates. Moreover, different substances were prime offenders in different profiles. These findings demonstrate that substance abuse is an important etiological contributor in some types of murderer but not in all types. PMID- 8193385 TI - Competency in adolescent inpatients. AB - A 15-item questionnaire was used to evaluate competency to consent to hospitalization in 30 adolescent psychiatric inpatients. For competency, 17 percent of the subjects met minimal clinical criteria, 30 percent met broad clinical criteria, and 37 percent satisfied legally oriented criteria. Only 22 percent of the adolescent subjects met combined clinical and legal criteria. When compared with previously studied adult voluntary and adult involuntary inpatients, the data more closely resemble those generated by involuntarily admitted adults. Consistently deficient performance on the minimal clinical criteria indicates that adolescents may have a poor understanding of the most general determinants of their hospitalization. Conversely, adolescents performed more favorably than voluntary and involuntary adults on the legally oriented criteria, demonstrating their better cognitive ability to understand such abstract concepts. Thus, specific types of judgment and insight may be essential components in the evaluation of adolescent competency to consent to psychiatric hospitalization. PMID- 8193386 TI - Noncompliance with family court mandated evaluations in a juvenile justice clinic. AB - This study identified factors correlating with noncompliance with family court ordered evaluations. Ninety charts from a juvenile justice clinic were reviewed. Subject noncompliance was defined as failure to attend three consecutive appointments. Patient, family, and environmental factors were analyzed. Forty-two percent of the subjects were noncompliant. Five variables discriminated compliant from noncompliant subjects: parental cooperation, prior criminal charge, school behavior problems, treatment at another facility, and disruptive behavior disorder. Utilizing these predictors, only 13 percent of subjects were misclassified as noncompliant in a discriminant analysis. It is concluded that a Court order by itself does not guarantee compliance with a mental health evaluation. However, the findings suggest that the risk for noncompliance may be assessed at the outset of the evaluation utilizing the above identified factors. PMID- 8193387 TI - Utilizing therapists to obtain death penalty verdicts. AB - As a result of recent decisions by the United States and California Supreme Courts, therapists now have been placed in a position in which they can be forced to testify in death penalty cases for the only purposes of achieving a conviction and a death penalty verdict. Zeal for the death penalty seems to have overcome any concern for the ethics of psychiatrists or even for the welfare of society. In California, therapists can now be forced to testify against their own patients in capital cases even if the patient does not tender his mental state as an issue, despite the presence of a psychotherapist-patient privilege in the state for criminal matters. In California, the only option for therapists who wish to treat potentially dangerous patients may be to conduct the therapy under the umbrella of attorney-client privilege. Otherwise they may not be able to avoid serious ethical problems and personal danger if the patient actually does kill someone during or after therapy. They may be unable honestly and ethically to treat such patients without obtaining truly informed consent to therapy under these potentially "undercover policeman" circumstances. Hopefully, professional organizations will take a more activist position, and courts will appreciate the folly of these decisions and reverse them. Otherwise, they may spread to other states, for which California frequently sets precedents. PMID- 8193388 TI - Child sexual abuse examinations: proposed guidelines for a standard of care. AB - A review of the literature regarding child sexual abuse examinations is presented and a proposal for a more objective and stringent standard of care is made. Current limitations in sexual abuse examinations include examiner bias, faulty procedures or diagnostic materials, and varied or conflicting roles of the judicial, social service, and mental health systems. Examiners in such cases should have adequate and specific training, be a neutral party appointed by the court, record the proceedings, and have access not only to the alleged victim, but also to the accused and to other parties during the examination. PMID- 8193389 TI - Carbamazepine lowers aggression: a review. AB - A small but growing number of reports document the antiaggressive effect of carbamazepine. Although it is supported by a small total number of patients studied with less than ideal rigor, the use of this medication as a means of reducing aggressive behavior is becoming an established clinical practice. The target diagnostic spectrum is broad, and the effect appears within days when it occurs. To promote both wider practice and further study, the authors summarize and briefly evaluate the reported investigations, single case studies, and articles related to the efficacy of carbamazepine for reducing aggression. Conceptual problems in aggression research, the relationships between epilepsy and aggression, possible mechanisms of action for this effect of carbamazepine, and practical clinical considerations are outlined. PMID- 8193390 TI - Intermediate care programs for inmates with psychiatric disorders. AB - Inmates with psychiatric disorders are a growing and difficult to manage population in federal and state prisons. An exploratory study was done of New York State's Intermediate Care Programs for inmates with psychiatric disorders. The study assessed whether there was a reduction in disruptive and harmful behaviors, and in the correctional restrictions and mental health services used to address those behaviors, among admissions to programs. Data came from corrections and mental health records of 209 inmates who had been in the program and prison for at least six months. Significant reductions were found in very serious rules infractions, suicide attempts, correctional discipline, and three mental health services: crisis care, seclusion, and hospitalization. PMID- 8193391 TI - Work-related stress in American trial judges. AB - This study examines work-related stress among American trial judges using a relational model of stress, which emphasizes an individual's appraisals in a person-situation relationship. A representative sample of 88 judges completed three questionnaires addressing type and magnitude of specific work-related stressors, psychological stress symptoms, and psychosocial moderators of stress. Factor analysis revealed five types of stressors: case, litigating party, purposes and consequences of decisions, conflicts between professional and personal values, and seriousness of a criminal offense. The most stressful aspects of work relate to poorly prepared or disrespectful counsel, exercising judicial management and discretion, and highly emotional cases under public scrutiny. Correlational analyses show that stress is associated with cognitive, emotional, and behavioral symptoms, including a possible adverse impact on decision-making capacity. Results are discussed in terms of the relational model of stress. PMID- 8193392 TI - Hospitalized insanity acquittees' level of functioning. AB - Since 1975 in New Jersey, similar legal criteria apply to the discharge of insanity acquittees as those patients who are civilly committed. Based on contact with insanity acquittees (NGRIs) in a regional state hospital, we had the impression that they appeared to be functioning better than the general inpatient population. The purpose of this study was to assess the length of inpatient stay and the level of functioning for the NGRIs and contrast it to a comparison group selected to for variables such as age, ethnicity, Axis I diagnosis, and history of substance abuse, which could impact on our variables of interest. We obtained psychiatrist-rated clinical global impression (CGI) scores and nursing-rated specific level of functioning (SLOF) scores in a group of 62 NGRIs and in a matched group of 62 controls. The NGRIs had significantly better CGI scores, and higher "personal care skills" and "social acceptability" SLOF section scores. The social acceptability subscale includes items for aggressiveness towards others, self, and property, all of which were significantly better for the NGRIs. Thus, in our setting, inpatient NGRIs displayed some evidence of better clinical functioning, including less perceived aggressiveness, than the control inpatients. Although the NGRIs has been in the regional state hospital for a shorter period than the controls, the NGRIs had spent an average of over three continuous years in secure facilities before transfer to the regional state hospital. We discuss our findings in view of high rates of paranoid subtypes of psychotic disorders among the NGRI group, and the high prevalence of substance abuse. PMID- 8193393 TI - Psychiatry and the death penalty: the landmark Supreme Court cases and their ethical implications for the profession. AB - The U.S. Supreme Court has made a number of recent rulings in regard to the death penalty that will likely have the effect of increasing the use of psychiatry during the trial and sentencing process in capital cases. Any such changes are bound to increase the number of ethical dilemmas faced by psychiatrists involved in such work. The rulings affecting psychiatry include: (1) The Eighth Amendment forbids the execution of persons who are mentally incompetent in regard to their ability to appreciate the reasons for punishment. (2) A mentally-ill prisoner may be forcibly given neuroleptics if he presents a danger to himself or others. (3) Forced medication may not be used during the trial and sentencing phase if it has the potential to change the defendant's demeanor significantly enough to affect his defense. (4) Aggravating psychological factors affecting a convictee may be balanced against mitigating factors in considering whether death sentence should be imposed. (5) The psychosocial impact of the crime upon the victim's family may be presented during the sentencing phase as factors relevant to sentencing. (6) Adolescents and retarded individuals are not immune from the death penalty simply by virtue of their age or level of intelligence. PMID- 8193394 TI - What is going on in erythema multiforme? PMID- 8193395 TI - Diagnosis and treatment of rosacea fulminans. AB - Rosacea fulminans is a rare disease of unknown cause which occurs exclusively in women well past adolescence. It was previously called pyoderma faciale because of its confinement to the face covering most of the surface with innumerable fluctuant inflammatory nodules and papules which frequently fuse and form monstrosities. Seborrhea prior to onset is typical. It is not a pyoderma; neither it is infectious or a variant of acne conglobata. The patients respond well to a therapeutic regimen including isotretinoin in combination with topical and systemic corticosteroids. The response is superior and much more rapid than in patients treated with oral antibiotics. Rosacea fulminans is the only indication for topical or systemic corticosteroids in the treatment of rosacea. Scarring is often minimal when the lesions clear. No recurrence is seen. PMID- 8193396 TI - Giant axonal degeneration: scanning electron microscopic and biochemical study of scalp hair. AB - Tightly curled 'frizzy' hair is a pathognomonic sign of giant axonal degeneration (GAD). The present study compares the morphological structure of the scalp hair of a GAD patient with that of her parents and first-degree relatives with the aid of scanning electron microscopy. The comparison included plaited hair of two age matched controls, in order to exclude mechanical plaiting artifacts. Trichorrhexis nodosa and fringing of the cut ends were exclusively found in the patient's hair. Longitudinal grooving was also frequently seen in hair of normal persons. Assay of carbon (C), sulfur (S) and nitrogen (N) contents of the patient's hair was normal, but the S:N ratio was significantly reduced, as compared with her relatives. However, comparison with a control group of non related healthy volunteers showed no difference. PMID- 8193397 TI - Increased proliferation of skin cells by sublethal doses of sodium lauryl sulfate. AB - Most quantitative in vitro approaches to determine irritancy have examined the potential of compounds to decrease biological functions or inhibit growth of cells. Irritants, however, are known to generally have the opposite effect in vivo, i.e. to stimulate cell division. This property has not been directly studied in vitro. We examined the ability of sublethal concentrations of sodium lauryl sulfate (SLS) to stimulate cultured keratinocyte and fibroblast proliferation in vitro. The growth of keratinocytes, without added growth factors, continuously exposed to SLS for 4 days was stimulated approximately 89% compared to control. Keratinocytes exposed to SLS for 1 or 18 h were stimulated 36 and 12%, respectively, over the next 4 days of growth. Subconfluent fibroblasts were also stimulated approximately 38%. Confluent fibroblasts were stimulated 40%. All stimulations were maximal between 10(-8) and 10(-5) M added SLS. Media conditioned by keratinocytes exposed to 10(-8) M SLS were able to increase the growth of naive keratinocytes by 117%. In all experiments doses of SLS > 10(-5) M inhibited cell growth. We conclude that sublethal doses of SLS can stimulate the growth of cultured keratinocytes and fibroblasts. The stimulation of growth seen may be related to the stimulation observed in in vivo irritation. PMID- 8193398 TI - Vitiligo and other diseases: coexistence or true association? Hamburg study on 321 patients. AB - In the past, several authors described an association of vitiligo with autoimmune disorders and the presence of different tissue autoantibodies. A review of the literature showed large differences in the results. Therefore, 321 patients with vitiligo (male/female ratio 114/207) were examined to see whether the frequencies of associated diseases and phenomena (i.e. Koebner phenomenon, canities praecox, halo nevi, poliosis circumscripta), the number of pigmented lesions and the presence of autoantibodies are of significance in order to support (a) a subentity of childhood vitiligo and (b) whether there is a true predisposition or association of autoimmune or other diseases in this group of patients. The data confirm earlier results of a prevalence of thyroid disease and the presence of thyroid antibodies, whereas other diseases are a random event. 6.2% of the patients had congenital nevi compared with 2.8% in a normal healthy population. Based on the results of this study and the significant higher risk for development of melanomas in this patient group, an annual checkup is recommended. PMID- 8193399 TI - Treatment of port-wine stains with the 585-nm flashlamp-pulsed tunable dye laser: a study of 74 patients. AB - Over 20 months, we have treated 74 patients (59 children less than 12 years of age) with port-wine stains (PWS) using a 585-nm flashlamp-pulsed dye laser (SPTL 1, Candela Corp., Wayland, Mass., USA) after topical anesthesia with Emla cream. A 5-point reference color scale was used to evaluate the results. 45 patients had at least one treatment on the entire surface of the lesion. A mean of 88 impacts per session was delivered. There was a significant decrease in color in around two thirds of the cases after one complete treatment with a gradual tendency to improvement after subsequent treatments. Younger age at the beginning of treatment was not found to be predictive of a better outcome after the first treatment. In around one third of the cases, positive test site treatment was not correlated with significant improvement after one treatment. Lesions situated on the limbs were less responsive than those on the head and neck. Except for problems due to absence of general anesthesia in young children enduring repeated stressful and sometimes painful procedures, the overall impression is that early treatment of PWS is possible with very limited risks of scarring using this technique. PMID- 8193400 TI - Immunohistopathological study of autoimmune pemphigus. Lack of strictly specific histological and indirect immunofluorescence criteria for paraneoplastic pemphigus. AB - Paraneoplastic pemphigus (PNP) is a form of pemphigus considered to bear characteristic immunohistopathological features (vacuolar-interface dermatitis, keratinocyte dyskeratosis and reactivity of patients' sera with transitional epithelia). The present study was undertaken in order to investigate whether these criteria are specific enough so as to allow the diagnosis of PNP in the absence of clinical data. A retrospective study of 66 biopsies of pemphigus revealed that one third of them comprised histological signs of PNP; one of the corresponding sera reacted with mouse bladder epithelium. However, no evidence of a neoplastic disease was present in any of the patients, and Western blotting further excluded the diagnosis of PNP. These results suggest that some of the features considered characteristic of PNP are not strictly specific for this variety of pemphigus; hence this diagnosis cannot be reliably established by histology or immunofluorescence but requires biochemical studies. PMID- 8193401 TI - Statistical definition of nail fold capillary pattern in patients with systemic sclerosis. AB - Image analysis of videographs of nail fold capillaries was performed in patients with systemic sclerosis (SS), and the capillary patterns were defined by canonical discriminant analysis. Forty-eight of 55 SS patients were significantly differentiated from patients with systemic lupus erythematosus and normal controls. Normal controls and patients with systemic lupus erythematosus showed identical nail fold capillary patterns; in patients with dermatomyositis the pattern was similar to that of SS. The canonical discriminant analysis revealed that only 5 of 55 (9%) SS patients showed a normal capillary pattern. The abnormal capillary pattern in SS patients correlated with microvascular disturbances such as Raynaud's phenomenon, digital pitting scars and low finger temperature. Our results indicate that quantitative analysis of the nail fold capillaries is useful in evaluating the microvascular disturbances in SS patients. PMID- 8193402 TI - Genetic polymorphisms in HLA-A, -B, -C and -DR antigens in Japanese patients with palmoplantar pustulosis. AB - Genetic polymorphisms in HLA-A, -B, -C and -DR antigens were investigated in 78 unrelated Japanese patients with palmoplantar pustulosis (PPP) and compared with a total of 472 normal persons. Only HLA-DR9 showed a significantly increased frequency among all HLA antigens investigated (chi 2 = 11.57, p < 0.001). It is suggested that major histocompatibility complex class II antigens including HLA DR antigen may determine the susceptibility to PPP and PPP may be a distinct disease entity from psoriasis. PMID- 8193403 TI - The association of HLA-B5 antigen with specific manifestations of Behcet's disease. AB - The HLA-B5 phenotype was investigated in 235 patients with Behcet's disease and in 100 healthy persons. HLA-B5 was more frequent in the patients (77 vs. 30% p < 0.001, relative risk = 7.8). The frequency of HLA-B5 was higher in patients with genital ulceration than without (82.3 vs. 63%, p < 0.01). Patients with thrombophlebitis showed a less frequent positivity of HLA-B5 antigen than the patients without thrombophlebitis (50 vs. 79.2%, p < 0.02). These results suggest that HLA-B5-related genes not only affect the development of Behcet's disease but also the occurrence of its clinical manifestations. PMID- 8193404 TI - Semiquantitative aspects of mast cells in normal skin and in neurofibromas of neurofibromatosis types 1 and 5. AB - Mast cells are supported to influence the growth of neurofibromas, because some of their mediators may also act as growth factors. Accordingly, mast cell stabilizers are claimed to reduce proliferation and itching of neurofibromas. Therefore, we quantified the mast cells of 19 neurofibromas and compared them with normal skin. We saw a statistically significant increase in mast cells in neurofibromas versus normal skin. However, there is no correlation between the age of neurofibromatosis (NF) patients and mast cell density. In our study the density of mast cells in neurofibromas is also independent of NF type; age of neurofibroma and chronic ultraviolet exposure in contrast to normal skin. Different tumors of the same patient had similar mast cell counts. PMID- 8193406 TI - Flame figures in bullous pemphigoid. AB - We report a patient with bullous pemphigoid showing prominent flame figures on skin biopsy. Although flame figures are the histological hallmark of eosinophilic cellulitis, they are occasionally seen in a variety of other dermatoses. PMID- 8193405 TI - Rapid diagnosis of Chlamydia trachomatis with a nucleic acid probe in male and female patients. AB - To evaluate a commercially available DNA hybridization test, the Gen-Probe Pace 2 assay (GP) was compared with the Chlamydiazyme (CZ) for the detection of Chlamydia trachomatis in urethral and endocervical specimens. Samples were collected from 300 persons, including 199 registered and 43 nonregistered female prostitutes, examined for screening purposes, as well as 22 male and 36 female symptomatic sexually transmitted disease (STD) patients. The overall prevalence of C. trachomatis was 7.3% in all persons examined with an infection rate of 20.9% in the nonregistered prostitutes, 2.5% in the registered prostitutes and 13.8% in the STD patients. The overall concordance of both diagnostic methods was 98.7% in all samples examined, 100% in male and 98.6% in female samples. Specimens with discordant results were further analyzed by a direct immunofluorescence test (MicroTrak) and by the probe competition assay (PCA). All samples only positive in the GP assay could be confirmed by the PCA while one result which was positive in the CZ could not be confirmed by any other test. The GP assay was superior to the CZ, when compared with true-positive and -negative results. The data demonstrate that the GP assay can be recommended as an alternative diagnostic technique to the CZ for Chlamydia diagnosis. PMID- 8193407 TI - Unusual coexistence of systemic lupus erythematosus and primary biliary cirrhosis. AB - Systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) are distinct clinical disorders which rarely occur in the same patient. We report on a 65-year-old woman with coexistence of both conditions. Diagnosis of SLE was ascertained by the presence of seven ACR criteria (cutaneous lesions, photosensitivity, antinuclear and anti-double-stranded-DNA antibodies, pancytopenia, arthritis, oral lesions). PBC was disclosed by clinical investigation, liver histology and highly positive antimitochondrial M2 antibodies. The most important differential diagnoses of lupus hepatitis are PBC and autoimmune hepatitis. Diagnostic criteria for these conditions are discussed, and previous reports on overlap between SLE and PBC are reviewed. PMID- 8193408 TI - A case of Hutchinson-Gilford progeria syndrome mimicking scleredema in early infancy. AB - We report a case of Hutchinson-Gilford progeria syndrome (HGPS). The patient showed the characteristics of scleredema at the age of 2.5 months but developed all the manifestations of HGPS gradually until 10 months old. The possibility of development of HGPS should by considered in any case of scleredema at birth or in early infancy. PMID- 8193409 TI - Papuloerythroderma and cutaneous T cell lymphoma. AB - An 83-year-old man had the typical cutaneous features of papuloerythroderma of Ofuji. There were reduced numbers of lymphocytes and platelets in his peripheral blood but the eosinophil count was normal. Skin biopsy showed a nondiagnostic infiltrate of T lymphocytes in the dermis. Treatment with topical steroids and UVB phototherapy was ineffective. Twelve months after presentation, a further skin biopsy revealed atypical lymphoid cells invading the epidermis and the skin adnexae. A diagnosis of malignant lymphoma was made; no evidence of extracutaneous spread was found. Photochemotherapy produced rapid resolution of the skin eruption and clearance of the cutaneous infiltrate. Papuloerythroderma may be a manifestation of a cutaneous lymphoma. PMID- 8193410 TI - Plasmasorbent therapy with activated charcoal column for congenital erythropoietic porphyria. PMID- 8193411 TI - Follicular graft-versus-host reaction. PMID- 8193412 TI - Facial flushing--a side effect of pulse therapy. PMID- 8193413 TI - A comparative histopathological examination of biopsies from patients with either the dominant or the Gamborg Nielsen type of hereditary palmoplantar keratoderma. PMID- 8193414 TI - NSAID use and efficacy in the emergency department: single doses of oral ibuprofen versus intramuscular ketorolac. AB - OBJECTIVE: To compare the clinical efficacy of single doses of intramuscular ketorolac and oral ibuprofen in the emergency department (ED) treatment of acute pain. DESIGN: A retrospective analysis of data collected during a prospective survey of pain management efficacy. The design was noninterventional, and therapy was selected by the treating physician independent of the trial. SETTING: Urban teaching hospital adult patient emergency department. PARTICIPANTS: A convenience sample of ED patients in acute pain. INTERVENTIONS: Patients received ibuprofen 800 mg po (n = 95), or ketorolac 60 mg im (n = 30) as a single dose. Therapy was selected by the treating physician and was not influenced by the study. RESULTS: Data collected were a 100-mm visual analog pain scale at patient arrival and discharge, verbal description of pain relief, patient demographics, pain management data, and discharge diagnosis. Baseline pain intensity was higher in patients receiving ketorolac (77 mm median) than in those receiving ibuprofen (65 mm, p = 0.02). Pain relief was similar (p = 0.29) with either treatment when assessed by visual analog scale or patient definition of pain relief. CONCLUSIONS: A single dose of either nonsteroidal antiinflammatory drug produced similar pain relief in the general ED population during clinical treatment of pain. Ketorolac should not necessarily be considered a more effective analgesic than ibuprofen in these commonly used doses. PMID- 8193415 TI - Penetration of intravenous and oral ciprofloxacin into sterile and empyemic human pleural fluid. AB - OBJECTIVE: To compare the penetration of oral and intravenously administered ciprofloxacin into infected (empyemic) and noninfected (sterile) human pleural fluid. DESIGN: Eleven men and 5 women (aged 29-76) were consecutively selected from adult patients referred to the respiratory unit for pleural effusion. In this open-label, prospective trial, 13 patients with sterile pleural effusions were nonrandomly assigned to receive either ciprofloxacin 200 mg (single intravenous dose), 750 mg (single oral dose), or 750 mg (two oral doses per day for 3 days); 3 patients with infected pleural effusions received 750 mg oral doses for 10 days. Simultaneous pleural fluid and venous blood specimens were drawn over 5 hours after single dose or when steady-state was attained, and ciprofloxacin concentrations were measured by HPLC. RESULTS: Pleural fluid concentrations of ciprofloxacin equaled plasma concentrations 1.5 hours after 200 mg was given intravenously and the pleural/plasma ratio remained > or = 0.9 for 4 hours. After a single 750-mg oral dose, pleural ciprofloxacin concentrations rose from 0 to 1.4 micrograms/mL over 5 hours with the highest pleural fluid/plasma ratio (0.7) at 5 hours. Average steady-state ciprofloxacin concentrations in sterile pleural fluid after 750 mg administered twice daily for 3 days, ranged between 1.1 and 1.8 micrograms/mL with ratios between 0.3 and 0.9 over 4 hours. In empyemic pleural fluid at the same dosage, average steady-state ciprofloxacin concentrations ranged between 1.9 and 3.4 micrograms/mL with ratios between 1.0 and 2.0 over 5 hours. CONCLUSIONS: Oral ciprofloxacin penetrates into sterile and empyemic pleural fluid with concentrations 30-90 percent and 100-200 percent of plasma concentrations, respectively. PMID- 8193416 TI - Chronic hemodialysis patients. Part I: Characterization and drug-related problems. AB - OBJECTIVE: To describe medication use in hemodialysis patients and to characterize the potential drug-related problems that may occur in this population. DESIGN: All patients being dialyzed during the study period who were responsible for taking their own medications and who were able to provide an accurate medication history were included in this study. A pharmacist administered a structured medication history and drug therapy review protocol known as the Focused Drug Therapy Review Program to identify potential drug related problems. This process was modified for a hemodialysis population. SETTING: Outpatient hemodialysis unit at a university-affiliated hospital. RESULTS: Thirty patients with endstage renal disease requiring hemodialysis were enrolled in the study. On average, 10 prescription and 2 prescribed nonprescription medications were used per patient. The incidence of potential adverse effects and medication allergies or intolerances averaged 5.5 and 2.2 per patient, respectively. Twenty patients (67 percent) reported missing an average of 3.4 (range 1-11) doses of medication per month. A total of 216 potential drug related problems (encompassing both prescribing choices and patient behaviors) were identified by the pharmacist; the categories of drug selection and medication compliance contained the greatest number of potential problems (24 and 23 percent, respectively). CONCLUSIONS: Hemodialysis patients use a large number of medications, which increases the risk for adverse reactions and other drug related problems. The types of potential drug-related problems identified are amenable to pharmacist input. Thus, such patients should be targeted for clinical pharmacy intervention. PMID- 8193417 TI - Chronic hemodialysis patients. Part II: Reducing drug-related problems through application of the focused drug therapy review program. AB - OBJECTIVE: To test the value and measure the impact of a model of pharmacy practice called the Focused Drug Therapy Review Program (FDTRP) in patients with endstage renal disease on hemodialysis. DESIGN: A modified version of FDTRP, adapted for a hemodialysis population, was assessed for its impact on prescriber behavior. The impact was measured by examining the percentage of pharmacist therapeutic recommendations accepted and implemented by the prescriber. SETTING: Thirty patients at a university hospital-based outpatient hemodialysis unit participated in the study. Twenty-four patients completed the study through the implementation evaluation. RESULTS: The pharmacist generated 114 therapeutic recommendations and 85 informative comments regarding drug therapy. The prescriber accepted 76 percent and implemented 70 percent of the therapeutic recommendations. The prescriber considered the informative comments to be helpful, even if the information was known previously. CONCLUSIONS: The FDTRP has been shown to be useful in the care of chronic hemodialysis patients. In addition, the pharmacist was able to provide clinically important recommendations in a closely monitored patient population. PMID- 8193418 TI - Metronidazole hypersensitivity. AB - OBJECTIVE: To report a case of a possible hypersensitivity reaction induced by metronidazole. CASE SUMMARY: An Asian woman with a history of recurrent vaginitis had previously developed localized erythema while on intravaginal metronidazole and nystatin. While receiving oral metronidazole for treatment of a current bacterial vaginosis, she developed chills, fever, generalized erythema, and a rash within 60 minutes of the first dose. Treatment with diphenhydramine was instituted. The following day while in the hospital, the patient's condition worsened; she experienced shortness of breath and increased edema of the extremities. Methylprednisolone was administered with diphenhydramine and her condition improved over the next 5 days. The patient's vaginitis was treated with gentian violet and she was discharged on a tapering dosage of prednisone. DISCUSSION: Metronidazole-induced cutaneous reactions and systemic hypersensitivity reactions are reviewed. Alternatives to metronidazole and other potential cross-reactive drugs are suggested for the treatment of recurrent vaginitis. CONCLUSIONS: Although the patient's initial reaction to metronidazole represented a rare event, written documentation and communication in the patient's native language may have prevented the subsequent severe hypersensitivity reaction. PMID- 8193419 TI - Pharmacokinetics of zidovudine and acetaminophen in a patient on chronic acetaminophen therapy. AB - OBJECTIVE: To report a case of a potential interaction between acetaminophen and zidovudine in a patient who had used high daily doses of acetaminophen over many years. CASE SUMMARY: A 43-year-old man presented with HIV-1 infection, recurrent oral candidiasis, and chronic use of acetaminophen, codeine, and diazepam before he started zidovudine therapy. Although literature was available regarding short term combined use of acetaminophen and zidovudine, information was lacking on zidovudine therapy and kinetics after long-term use of acetaminophen. Acetaminophen and zidovudine pharmacokinetics were determined on several occasions. The results showed extremely rapid absorption of both drugs (tmax the time to reach maximum concentration, 10-15 minutes for acetaminophen and 15-20 minutes for zidovudine) and, consequently, relatively high maximum plasma concentration (Cmax). No influence on other pharmacokinetic parameters of either drug could be detected. Because the effect of high Cmax values of zidovudine is unknown, the patient was treated with a third of the dose of zidovudine used at that time (zidovudine 100 mg q6h). No toxicity or opportunistic infections developed within the next 8 months, after which the patient died of a cause unrelated to HIV infection. DISCUSSION: The observed pharmacokinetic profiles of both drugs are discussed and compared with two studies dealing with zidovudine therapy in combination with short-term use of acetaminophen and with a case report of acetaminophen-induced hepatotoxicity during concomitant use of zidovudine. CONCLUSIONS: Long-term use of acetaminophen may accelerate the absorption of zidovudine. Although other causes cannot be ruled out, there was no influence on other pharmacokinetic parameters of zidovudine. No influence of zidovudine on acetaminophen concentrations was found. Combined use of zidovudine 100 mg q6h and acetaminophen 500 mg q4h appeared to be safe and effective for at least eight months. PMID- 8193420 TI - Ondansetron for treating nausea and vomiting in the poisoned patient. AB - OBJECTIVE: To describe the efficacy of ondansetron for the treatment of poisoning associated vomiting in two patients following drug intoxication. PATIENTS: Two self-poisoned adolescent patients. INTERVENTION: Intravenous ondansetron. RESULTS: Resolution of nausea and vomiting in both patients. CONCLUSIONS: Ondansetron appears to be a very effective antiemetic drug for use in selected intoxicated patients. PMID- 8193421 TI - Otic administration of amphotericin B 0.25% in sterile water. AB - OBJECTIVE: To report otic administration of parenteral amphotericin B 0.25% in sterile water. CASE SUMMARY: A 44-year-old HIV+ man was diagnosed with otitis externa. The patient's past medical history was remarkable for positive Coccidioides immitis serology for more than five months, essential hypertension, and Barrett's esophagitis. Culture results from an ear swab revealed 4+ Aspergillus fumigatus and 3+ Staphylococcus, coagulase negative. Antiinfective therapy for the otitis externa included oral and topical antibacterial and antifungal medications. Amphotericin B 0.25% in sterile water was prepared by the pharmacy for topical otic administration. The otic amphotericin B was dispensed with instructions to refrigerate and assigned a one-week expiration date. The prescription called for instillation of 1-2 drops in each ear three times a day. The patient's signs and symptoms of otitis externa resolved during several weeks of antiinfective therapy. Topical administration of amphotericin B 0.25% in sterile water was not associated with any local adverse effects in this patient. DISCUSSION: The rationale for use of the parenteral amphotericin B formulation to prepare an otic dosage form, and the rationale for the specific concentration and expiration date chosen are discussed. CONCLUSIONS: This patient tolerated topical otic administration of amphotericin B 0.25% in sterile water when administered three times daily. PMID- 8193422 TI - Potential quinolone-induced cartilage toxicity in children. PMID- 8193423 TI - Guanethidine for reflex sympathetic dystrophy. PMID- 8193424 TI - High-dose interferon alfa-2A for the treatment of chronic hepatitis C. PMID- 8193426 TI - Oral antihypertensives for hypertensive urgencies. AB - OBJECTIVE: To review the data describing the use of oral antihypertensive agents in the treatment of hypertensive urgencies (HU). DATA SOURCES: A MEDLINE search of the English-language literature and fan searches of papers evaluating oral antihypertensives in HUs and emergencies were conducted. STUDY SELECTION: Controlled and uncontrolled studies in humans are reviewed. Emphasis was placed on recent trials evaluating individual agents and comparative trials. DATA SYNTHESIS: Comparative trials have demonstrated that four currently available oral agents can lower blood pressure rapidly and predictably. Nifedipine, the most extensively studied, and clonidine have served traditionally as the oral agents of choice for the treatment of HUs. All the agents can lower blood pressure effectively within the first few hours after dosing, but their use also has been associated with adverse effects. Nifedipine and captopril are the two agents with the most rapid onset, within 0.5-1 hour, and may treat hypertensive emergencies as well as urgencies. Clonidine and labetalol have maximal blood pressure lowering effects at 2-4 hours. CONCLUSIONS: Captopril, clonidine, labetalol, and nifedipine are all effective agents for the treatment of HUs. Agent selection should be based on the perceived need for urgent blood pressure control, the cause of HU, and concomitant conditions. A definite benefit from acute blood pressure lowering in HUs has yet to be demonstrated, especially in asymptomatic patients. More controlled trials with less aggressive dosing regimens and placebo controls need to be performed to assess the most appropriate treatment for HUs with the fewest adverse effects. PMID- 8193425 TI - Lipoprotein(A): physiologic function, association with atherosclerosis, and effects of lipid-lowering drug therapy. AB - OBJECTIVE: To review the structure and physiologic function of lipoprotein(a) [Lp(a)], review the association of Lp(a) with the development of atherosclerosis, and to critically evaluate the current literature regarding the effects of lipid lowering drug therapy on Lp(a) serum concentrations. DATA SOURCES: English language clinical and animal studies, abstracts, and review articles pertaining to Lp(a). STUDY SELECTION AND DATA EXTRACTION: Relevant human and animal studies examining Lp(a)'s role in atherosclerosis and the effect of drug therapy on Lp(a) serum concentrations. DATA SYNTHESIS: Possible physiologic functions and potential atherogenic mechanisms of Lp(a) are discussed. Evidence supporting the association of Lp(a) with atherosclerosis is presented. Studies evaluating the effects of lipid-lowering drug therapy on Lp(a) concentrations are reviewed and critiqued. CONCLUSIONS: Lp(a) concentrations are correlated with the risk of atherosclerotic vascular disease (AVD) in both animals models and human studies. Drug therapies that have produced a consistent reduction in Lp(a) concentration include niacin alone or in combination with a bile acid sequestrant or neomycin. However, additional, larger studies are needed to evaluate the ability of drug therapies to specifically reduce elevated Lp(a) concentrations. Preliminary information suggests that reduction in Lp(a) concentrations may be associated with atherosclerotic plaque regression. Although drugs are available to lower Lp(a), one cannot conclude that lowering of Lp(a) is warranted until clinical trials demonstrating beneficial effects have been published. PMID- 8193427 TI - Hypertension and endstage renal disease. AB - OBJECTIVE: To review current literature regarding the development of hypertensive renal disease, its epidemiology, and its pathophysiology. This review focuses on strategies to slow or halt the progression of endstage renal disease (ESRD) in hypertension, including the role of blood pressure control, different types of antihypertensive agents, early treatment, and dietary considerations. DATA SOURCES: Information was retrieved from searching the MEDLINE database for articles consisting of epidemiologic studies, clinical studies, and review articles pertaining to hypertension and ESRD. Information also was obtained from the US Renal Data System annual data reports. STUDY SELECTION: Emphasis was placed on clinical trials in the English language addressing issues in hypertension and ESRD. Clinical trials reporting relationships between blood pressure control and ESRD, as well as those comparing different antihypertensive agents, were evaluated. DATA EXTRACTION: The methodology and results from clinical trials were evaluated. Studies were assessed according to the measures of renal function used, baseline data collected, degree of blood pressure control, and antihypertensive therapy. DATA SYNTHESIS: Clinical trials including patients with essential hypertension, diabetes mellitus, and renal insufficiency of various etiologies were evaluated. The recommendations from these evaluations were based on study design and the types of populations used (i.e., blacks vs. whites, diabetics vs. nondiabetics). CONCLUSIONS: Blood pressure control is currently the most important strategy to slow or halt the progression of renal insufficiency in hypertensive individuals. Whether specific antihypertensives are renal protective is still controversial, but results from clinical trials are promising. PMID- 8193428 TI - Treating isolated systolic hypertension in the elderly. AB - OBJECTIVE: To review the prevalence, pathophysiology, vascular risk, and treatment of isolated systolic hypertension (ISH) in the elderly. DATA SOURCE: A MEDLINE search of the English language literature was performed to identify pertinent literature. Key search terms were hypertension, systolic, and elderly. STUDY SELECTION: All studies available evaluating drug therapy for ISH or hypertension in the elderly as well as review articles discussing the prevalence, pathophysiology, and treatment of ISH were selected. SYNTHESIS: ISH occurs commonly in the elderly and is associated with increased risk for cardiovascular and cerebrovascular disease. Although the mechanism for ISH in the elderly is not completely understood, the primary factor is believed to be a reduction in arterial compliance. Results of the Systolic Hypertension in the Elderly Program demonstrated that control of ISH using a diuretic alone or in combination with a beta-blocker significantly reduced the incidence of strokes and cardiovascular events. In this trial, drug therapy was found to be safe and generally well tolerated by the elderly. Newer antihypertensive agents such as the calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors have also been shown to effectively lower SBP in the elderly, but the effects on long-term morbidity and mortality are not yet known. CONCLUSIONS: ISH is an important risk factor for vascular disease in the elderly. Accurate diagnosis and effective drug treatment can result in significant reductions in the risk of cardiovascular and cerebrovascular events. Based on the available trial data, diuretics appear to be the drugs of first choice unless there are contra-indications. If combination drug therapy is required, beta-blockers should be considered although their contribution to vascular risk reduction remains less clear. Additional studies are needed to determine the long-term benefits and risks of alternative antihypertensive agents such as calcium-channel blockers and ACE inhibitors. PMID- 8193429 TI - Fluorouracil cardiotoxicity. AB - OBJECTIVE: To review the clinical manifestations, postulated mechanisms, and therapeutic implications of fluorouracil-induced cardiac toxicity. DATA SOURCE: A MEDLINE search was used to identify pertinent literature. STUDY SELECTION: Studies and case reports on fluorouracil cardiotoxicity were identified through a MEDLINE search. A manual review of bibliographies of identified articles was performed to ensure that all pertinent articles were included. DATA EXTRACTION: Data pertaining to all aspects of fluorouracil cardiac toxicity, including pathogenesis, predisposing factors, clinical manifestations, and therapeutic implications, were evaluated. DATA SYNTHESIS: Estimates from large series suggest a 1.6-2.3 percent incidence of clinically demonstrated cardiotoxicity. Predisposing factors include the presence of coronary artery disease and concurrent radiotherapy. Postulated mechanisms include direct myocardial ischemia, coronary spasm, or cardiotoxic impurities in fluorouracil formulation. Clinical manifestations include chest pain, nausea, diaphoresis with typical ischemic electrocardiographic (ECG) changes, relieved to normal after stopping the drug therapy. Nitrates and calcium-channel blockers do not protect against cardiotoxicity. CONCLUSIONS: Fluorouracil cardiotoxicity may be much more common and clinically significant than previously thought. A high index of suspicion for cardiotoxicity must be maintained when the drug is administered, especially in the presence of heart disease and concomitant radiation therapy. In the presence of chest pain, it is mandatory to stop the infusion and, if possible, to replace fluorouracil with another chemotherapeutic agent. PMID- 8193430 TI - Cyclosporine monitoring improves graft-versus-host disease prophylaxis after bone marrow transplantation. AB - OBJECTIVE: The principal objective of this study was to determine whether a relationship exists between trough cyclosporine concentrations measured by HPLC and the development of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. DESIGN: A retrospective analysis of 59 consecutive human leukocyte antigen-matched bone marrow transplants. Patients received uniform GVHD prophylaxis with cyclosporine and methotrexate. Whole blood trough cyclosporine concentrations were measured at least twice weekly during hospitalization and weekly after discharge. SETTING: A dedicated bone marrow transplant unit in an academic center. MAIN OUTCOME MEASURES: The means of cyclosporine concentrations were assessed for each patient on a weekly basis during the first 50 days after transplant. These means were compared between patients developing grade 2-4 acute GVHD and patients without significant GVHD. RESULTS: Eighteen patients developed acute GVHD at a median of 25 days after bone marrow transplant (range 10-50). There was no correlation between the development of GVHD and patient age, diagnosis, donor age, donor gender, donor-recipient gender mismatch, and time to neutrophil engraftment (> 1000 x 10(6) cells/L). Although mean weekly cyclosporine concentrations were consistently lower in patients developing acute GVHD, the difference in values compared with those of patients with GVHD was not statistically significant. Mean weekly cyclosporine concentrations at the time of neutrophil engraftment were statistically associated with the development of GVHD. Patients with GVHD had mean +/- SD concentrations of 174 +/- 69 ng/mL, significantly lower than 254 +/- 114 ng/mL in patients without GVHD. Furthermore, the rate of GVHD was 82 percent in patients with mean concentrations < 200 ng/mL at the time of neutrophil engraftment as compared with a rate of 34 percent in patients with concentrations > or = 200 ng/mL (relative risk = 2.4). Also, mean cyclosporine concentrations measured during the week of onset of GVHD were significantly lower compared with mean cyclosporine concentrations of all other patients at risk of GVHD during that week. CONCLUSIONS: Cyclosporine concentrations are associated with the development of acute GVHD. Patients with HPLC whole blood concentrations < 200 ng/mL are at significantly higher risk of developing GVHD, particularly if these concentrations are observed during the week of neutrophil engraftment. More effective GVHD prophylaxis could be achieved by careful monitoring of cyclosporine concentrations after transplant. PMID- 8193431 TI - Pharmacoeconomic analysis of cefmenoxime dual individualization in the treatment of nosocomial pneumonia. AB - OBJECTIVE: To determine if dual individualization of cefmenoxime dosing is cost effective. DESIGN: Retrospective, pharmacoeconomic decision analysis of two consecutively conducted prospective clinical studies. PATIENTS: Patients with documented gram-negative nosocomial pneumonia were evaluated. Thirty-three patients received cefmenoxime at standard dosing and 28 patients received doses according to dual individualization methodology. MAIN OUTCOME MEASURE: Antibiotic and infection-related costs were compared between groups. The number of hospital antibiotic days and costs incurred on those days were also evaluated. A decision model was constructed to characterize differences in treatment outcome. Probabilities within the decision tree were derived from 61 evaluable patients. Cost-effectiveness and incremental cost-effectiveness ratios were calculated. Sensitivity analysis was performed by varying outcome probabilities, antibiotic prices, and hospital room costs. RESULTS: Antibiotic and infection-related costs (mean +/- SEM) were $848 +/- 78 for standard cefmenoxime dosing and $1123 +/- 128 for dual individualization (p < 0.05). Total hospital costs were $10,660 +/- 1432 for standard dosing and $11,709 +/- 1900 for dual individualization (p > 0.05). Median antibiotic length of stay (ALOS) was 15.2 and 12.7 days for standard and dual individualization methodologies, respectively (p > 0.05). Incremental analysis of cost-effectiveness indicated that a similar reduction in length of stay for 259 dual individualization patients would save $321,808 annually. CONCLUSIONS: Sensitivity analysis indicates that, by reducing ALOS, dual individualization could be a cost-effective method of beta-lactam dosing for patients with pneumonia. A prospective study should be conducted to validate these findings. PMID- 8193432 TI - Using the "smart pill" to teach about substance abuse. PMID- 8193433 TI - Theophylline disposition in Korean patients with congestive heart failure. AB - OBJECTIVE: This study proposed to determine the systemic disposition of theophylline in Korean adult patients during decompensated congestive heart failure compared with disposition after recovery. DESIGN: An experimental, prospective, self-controlled, nonrandomized design was used. SETTING: The study was performed in a general community hospital located in Pusan, Korea. PATIENTS: Eight nonsmoking elderly Korean patients with decompensated congestive heart failure presenting to the emergency department were included in the study. Consecutive patients who met entrance criteria were selected. All patients completed the study. INTERVENTIONS: A single dose of aminophylline 6 mg/kg was administered by intravenous infusion over 30 minutes. Standard methods of congestive heart failure therapy were used in each patient, including bed rest, restriction of sodium, and drug therapy including digoxin. After compensation of congestive heart failure was achieved, the theophylline infusion was repeated. OUTCOME MEASURES: Serum theophylline concentrations were measured at 2, 6, 12, and 18 hours after completion of the dose at baseline and following treatment. RESULTS: A clinically and statistically significant improvement in mean theophylline total body clearance was demonstrated following treatment (from 21.7 +/- 2.8 to 43.4 +/- 4.7 mL/kg/h [mean +/- SEM]; p < 0.01). Comparison of these results with a computer model based on literature averages of peoples of all nationalities showed significant underprediction of theophylline clearance both before (p < 0.05) and after (p < 0.01) treatment. The theophylline elimination half-life prior to treatment was 18.2 +/- 2.2 hours and decreased to 9.1 +/- 0.8 hours following treatment (p < 0.01). There was no statistical difference between the computer-model predicted initial theophylline half-life and the measured value, but the model significantly underpredicted the improvement following treatment. CONCLUSIONS: The improvement in theophylline clearance demonstrated in this study appears to be greater than that reported for Western patients. This has practical application to the calculation of appropriate theophylline maintenance dosage regimens in Korean patients with cardiac failure. These data support the need for consideration of racial differences in individualizing dosage regimens. We suggest that all kinetic models, whether software supported or not, should consider incorporating ethnic origin as a demographic factor that helps select the proper model for individual patients. PMID- 8193434 TI - Stroke following application of a nicotine patch. PMID- 8193435 TI - Multisystem hypersensitivity reaction to carbamazepine. PMID- 8193436 TI - Ventricular arrhythmias associated with flosequinan. PMID- 8193437 TI - Trimethoprim/sulfamethoxazole kinetics in children with biliary atresia. PMID- 8193438 TI - Is it safe to combine a selective serotonin reuptake inhibitor with selegiline? PMID- 8193440 TI - Reversible neutropenia and thrombocytopenia during famotidine treatment. PMID- 8193439 TI - Hypoglycemia caused by maprotiline in a patient taking oral antidiabetics. PMID- 8193441 TI - Reactive effects of measurement of pain. AB - OBJECTIVE: Self-rating procedures that repeatedly focus the patient's attention on pain may change the experience of pain. This experiment was designed to determine whether repeated clinical pain measurement alters perceived pain intensity and distress. PATIENTS AND SETTING: Fifty-four low-back-pain patients (26 men, 28 women) who were referred to, but had not yet attended, a back-care class in a teaching hospital. DESIGN: Random assignment was made to one of three groups, each of which completed a different self-monitoring task daily for 8 days. Group 1 completed the McGill Pain Questionnaire; group 2 recorded their pain using a briefer pain diary; and group 3, a control group, kept a checklist of foods consumed, with no reference to pain. DEPENDENT MEASURES AND HYPOTHESES: Before and after the self-monitoring period, all three groups estimated their worst, least, and usual pain and their pain-related emotional distress, using visual analog scales. It was hypothesized that group 1 would produce the highest posttest ratings of pain and distress and group 3 the lowest. RESULTS: Means on all four dependent measures were virtually identical across groups; analyses of covariance confirmed that none of the between-group differences approached significance. CONCLUSIONS: The results suggest that daily self-monitoring of chronic clinical pain does not alter subjective pain intensity. Reactive effects of measurement that have been identified in studies of experimental and acute clinical pain probably take place on a much shorter time scale and thus may not be influential in daily measurement of long-term clinical pain. PMID- 8193442 TI - The problem-oriented psychiatric examination of the chronic pain patient and its application to the litigation consultation. AB - OBJECTIVE: The purpose of this paper is (a) to delineate the behavior problems or complaints of chronic pain patients (CPPs) as presented in the literature and to add those behavior problems that have not yet been identified; (b) to present a semistructured psychiatric interview format that would lead to the delineation of these problems; and (c) to present a format and structure for the proposed semistructured psychiatric interview that could be utilized for the purposes of medicolegal assessment of the CPP and the reporting of that assessment to the litigation process. SETTING: Any psychiatric/psychological examination of the CPP. METHODS: The pain literature was reviewed for any research reports that specifically addressed or delineated the types of behavior problems found within the chronic pain (CP) population. These behavior problems were placed in a semistructured interview format, organized in such a way as to facilitate reporting to the litigation process if necessary. RESULTS: This semistructured psychiatric examination format is presented. Controversial problem areas in this format are discussed with appropriate references. CONCLUSIONS: CPPs are seen for the psychiatric examination with a set of behavioral problems largely determined by their medical condition, the consequences of that condition, and the social circumstances surrounding that medical condition (e.g., the litigation process). The psychiatric examination should be tailored to this special set of problems. PMID- 8193443 TI - Sensory and affective predictors of overall pain and emotions associated with affective pain. AB - OBJECTIVE: Psychological scaling techniques consistently produce separate ratings for sensory and affective components of pain. This study examines the relative contributions of these components to pain as a whole and the contributions of different emotions to the affective component of pain. DESIGN: The design was correlational. Visual analogue scales were used to quantify overall pain, sensory pain, affective pain, and individual emotions. These data lent themselves to regression techniques for expressing pain as a function of sensation and affect as a function of emotion types. SETTING: Data were collected at the Pain Clinic within the Department of Physical Medicine at the Ohio State University. PATIENTS: Subjects were 40 chronic pain sufferers admitted to an inpatient pain management program. RESULTS AND CONCLUSIONS: Ratings of overall pain were not a simple summation of sensory and affective ratings, but a linearly additive function of both component ratings each with a unique weighting. The affective component of pain was a function of three differentially weighted sets of emotions, anger, fear, and sadness being most salient. Implications arise for the broader assessment of chronic pain and the treatment of specific emotions that may be particularly associated with the pain. PMID- 8193444 TI - Respiratory-related critical events with intravenous patient-controlled analgesia. AB - OBJECTIVE: The objective of this study was to identify the underlying causes of respiratory-related critical events associated with intravenous patient controlled analgesia (i.v. PCA). DESIGN: The design is an observation study of prospectively collected data. SETTING: An Acute Pain Service (APS) was established for the management of all patients receiving i.v. PCA therapy for pain management. As part of ongoing care, all respiratory-related critical events were documented and analyzed by staff members of the APS team. PATIENTS: All patients receiving i.v. PCA therapy through the APS during the period of May 1990 through October 1992 were enrolled in the study. INTERVENTIONS: Evaluation of all respiratory-related critical events was attempted to identify the underlying cause of the event and to determine if measures could be taken to prevent recurrence of similar events. OUTCOME MEASURES: Any clinical event that could have or did lead to adverse patient outcome was used as an outcome measure. RESULTS: A total of 3,785 patients received PCA therapy for a total of 11,521 patient care days. Fourteen critical events occurred, of which four led to increased patient care. There were eight programming errors (all involving misprogramming of the continuous infusion): three involved a family member activating the device, three were the result of an error in clinical judgment, and one involved a patient tampering with the device (one event involved more than one error). Of the four events that led to increased patient care, two involved a family member activating the device, one was the result of a programming error, and one was the result of an error in clinical judgment. All patients who experienced a critical event had an uneventful recovery. CONCLUSIONS: Following review of the critical events, it was determined that the design of the PCA device contributed to the misprogramming errors and the device was removed from service. Changes in the training of physicians and nurses were instituted to avoid recurrence of other errors identified. The incidence of serious respiratory-related critical events was 0.1%. i.v. PCA therapy has the risk of potentially serious complications and requires constant physician and nursing care with an active quality assurance program. PMID- 8193445 TI - Role of psychological factors in postoperative pain control and recovery with patient-controlled analgesia. AB - OBJECTIVE: We examined the extent to which preoperative state and trait anxiety, general need to control, need to control analgesia, expectations regarding postoperative pain, and demographic variables predict the severity of postoperative pain, discomfort, anxiety, duration of recovery, and patient controlled analgesia (PCA) behaviors. DESIGN: Preoperative and outcome variables were analyzed using Pearson product-moment correlations and forward stepwise multiple linear regression. SETTING: This study was conducted at a university hospital in preoperative and postoperative settings. PATIENTS: Ninety-nine consecutively consenting ASA physical status I-II women (age 46 +/- 11 years, 70% caucasian, 28% Afro-American, 2% Hispanic) undergoing simple hysterectomy procedures with no known cancer were included in the study. INTERVENTIONS: Standardized general anesthesia, surgery, and PCA therapy was conducted. OUTCOME MEASURES: The McGill Pain Questionnaire (MPQ), patient requests and delivered analgesic medication, visual analog scales (VAS) for pain and anxiety, time to oral medications and hospital discharge, and Likert scale measurements of overall pain and discomfort were utilized. RESULTS: Older patients generally reported less pain, but used the same amount of analgesic medication as younger patients. Preoperative trait anxiety correlated with increased PCA requests, but not with postoperative pain. In contrast, preoperative state anxiety correlated positively with postoperative pain and with shorter time to hospital discharge. The patients' need for control was positively correlated with the Present Plan Index scale of the MPQ, with morphine requirement, and with PCA requests. CONCLUSIONS: Psychological factors do influence postoperative recovery and pain control in women receiving PCA therapy after abdominal hysterectomy, and attention to individual patient differences may lead to improved postoperative outcomes. PMID- 8193446 TI - Patterns in low back pain hospitalizations: implications for the treatment of low back pain in an era of health care reform. AB - OBJECTIVE: To examine patterns in both surgical and nonsurgical low back pain (LBP) hospitalizations through time and among geographic regions and to explore the practical implications of these patterns for health care reform. SETTING: For time trends, the U.S. (1979-1987); for geographic variations, major regions of the U.S. (1987). DATE SOURCE: The National Hospital Discharge Survey. RESULTS: Rates of both surgical and nonsurgical LBP hospitalization varied twofold among regions of the U.S., and average lengths of stay for these types of hospitalization varied considerably as well. The U.S. rate of LBP surgery increased sharply during the period covered by the study. Over the same time, the U.S. rate of nonsurgical LBP hospitalization declined, as did average lengths of stay for both types of LBP hospitalization. CONCLUSION: Wide variations in LBP hospitalization practices raise the issue of which practices are most appropriate. Outcomes research addresses this issue, as does research on patient preferences for certain types of treatment. As indicated by the increasing rate of LBP surgery, more research also needs to be done on changing physician practice style. If such research were to result in a reduction in LBP hospitalization, savings in health care costs would be considerable. PMID- 8193447 TI - Stability of temperature asymmetries in reflex sympathetic dystrophy over time and changes in pain. AB - OBJECTIVE: To determine the clinical usefulness of skin temperature patterns for tracking reflex sympathetic dystrophy (RSD) by assessing (a) long-term relationships between changes in pain due to RSD and patterns of near surface blood flow and (b) relationships between site of pain and site of greatest asymmetries in near surface blood flow patterns. DESIGN: Multiple videothermographic evaluations of near surface blood flow patterns were performed on subjects diagnosed as having RSD. At each session, subjects filled in an outline of the body to show the location, intensity, and description of their pain. The thermograms were evaluated independently by two raters for location and intensity of pain, as well as location and degree of temperature asymmetries. SETTING: Two Army Medical Centers. SUBJECTS: Thirteen male and 16 female subjects were subsequently diagnosed as having RSD. OUTCOME MEASURES: Ratings of pain and videothermograms of the lower limbs were used as outcome measures. RESULTS: All but one subject were usually cooler on the most painful side by at least 0.5 degrees C. The amount of relative coolness was not proportional to pain intensity. There were no consistent overlaps between exact location of pain and greatest thermal asymmetry. Seven subjects were thermally symmetrical on at least one recording. Six subjects were warmer on the affected side on at least one recording. One subject was always warmer on the affected side. CONCLUSIONS: Videothermography is not an appropriate tool to use alone for either single session diagnosis or multi-session tracking of RSD. PMID- 8193448 TI - Coping with taxonomy. PMID- 8193449 TI - Assessing the impact of the All-Wales Mental Handicap Strategy: a survey of four districts. AB - The All-Wales Mental Handicap Strategy (AWS) pledged government leadership and additional resources for the task of developing community based residential, domiciliary, respite, daycare and professional services for people with mental handicaps and their families throughout Wales. Ultimately, the authors of the AWS sought to affect for the better the extent to which people with mental handicaps experience typical community life. A large random sample of people with mental handicaps in four diverse districts was used to track changes in services received, professional input, involvement in individual planning, the number of community activities pursued, and the size and range of individuals' social networks across the middle 4 years of the AWS. The balance between private housing and service residence remained unchanged although, with the ageing of the cohort, there was a decrease in the proportion living with parents and an increase in those living independently or in another family situation. There was an increase in the availability of residential services in the form of ordinary housing and an associated contraction in large congregate care facilities. However, not all moves were towards more ordinary living. Some people moved from large statutory sector specialist facilities to other atypical forms of residence, as did some people from family homes. Family support services in the form of family aides and short-term care increased significantly, but indicators still suggest that an expansion of these services is merited. Day services diversified slightly, but without affecting the major role of the traditional centre. There was a decrease in the numbers receiving a fulltime service. Only a third of the sample received regular individual plan reviews of the services they received and the developmental goals set in their name. In general, individuals were involved in a greater number of community activities that brought them into contact with other citizens. However, such an increase has not led to significant changes in the size or composition of people's friendship networks. Overall, the changes in service provision and family and user experience have been in line with the direction set by the AWS. However, the degree of change still required before the new pattern of services envisaged by the AWS is substantially in existence, or the experience of people with mental handicaps conforms with the guiding principles which underpin it, is considerably greater than that achieved after 7 of its initial 10 years. PMID- 8193450 TI - Restraint fading and the development of alternative behaviour in the treatment of self-restraint and self-injury. AB - Restraint fading and differential reinforcement were used to reduce the self injurious behaviour (SIB) and self-restraint of a profoundly retarded man. The variables maintaining both behaviours could not be identified via pre-treatment functional analysis; however, self-restraint exerted at least some stimulus control over SIB. In Phase 1, the subject's topography of self-restraint (wrapping arms in shirt) was replaced with another topography (wrapping wrists in towel) that could be more easily faded to a headband. However, the subject's restraints could not be completely faded, and any movement was accompanied by SIB; thus, in Phase 2, a compliance training procedure was implemented to reduce his SIB while increasing time out of restraint. In Phase 3, the subject was taught to mand for edibles during training sessions. Results indicated that restraint fading combined with the development of alternative behaviour could be an effective treatment procedure for those who engage in both self-restraint and SIB. PMID- 8193451 TI - Oral zinc supplementation in Down's syndrome subjects decreased infections and normalized some humoral and cellular immune parameters. AB - The effect of 4 months of oral zinc supplementation on immune functions in non institutionalized young female and male Down's syndrome (DS) subjects was studied. Along with plasma levels of zinc, the immune parameters, measured before and after zinc treatment, were plasma levels of thymulin, the percentage and the absolute number of circulating white blood cells, total lymphocytes, lymphocyte subpopulations, the mitogen-induced lymphocyte proliferation, the production of interleukin-2, and the activity of stimulated granulocytes. Some immune parameters were significantly influenced by zinc treatment. In particular, a normalization of thymulin and zinc plasma levels were found in these subjects after zinc supplementation. At the end of the clinical trial, in vitro lymphocyte proliferation and polymorphonuclear activity also increased and reached normal values. Zinc administration exerted a positive clinical effect in these children, since a reduced incidence of infections was found. PMID- 8193452 TI - Leisure activities of young adults not receiving mental handicap services who were in a special school for mental handicap as children. AB - The subjects of this study were 22-year-old adults who had attended a special school for children with mental handicap. Since leaving school, they had dropped out of the mental handicap services. The subjects' leisure activities were compared with peers who had always attended regular classes as children. The subjects engaged in fewer types of activities than the comparisons and had fewer activities that involved interpersonal relations, especially with non-family peers. The size of these differences was influenced by marital status. PMID- 8193453 TI - A stimulus control procedure to increase requesting with individuals who are severely/profoundly intellectually disabled. AB - Various procedures have been used to establish and increase manual signed and spoken requesting with individuals who are intellectually disabled. A few studies have used the so-called blockable response conditioned establishing operation (BR CEO) as a stimulus control procedure to increase requesting. A variation on the BR-CEO is the interrupted chain procedure, in which requesting for the activity that had been interrupted is reinforced by continuation of the activity. Rather than interrupting an ongoing activity, six individuals who are severely/profoundly intellectually disabled were studied with respect to the differential effectiveness of presenting them incomplete versus complete referents (i.e. activity and objects) as a consequence of their requesting on their rate of requesting. Data were collected within a reversal design. The results show that five out of six individuals more than doubled their rate of requesting. Incomplete presentation of referents may be a practical procedure to increase requesting. PMID- 8193454 TI - Lithium treatment for people with learning disability: patients' and carers' knowledge of hazards and attitudes to treatment. AB - Twenty-five people with a learning disability who were receiving lithium were assessed with regard to their knowledge of lithium and its adverse effects, and their attitude to treatment. Questionnaires developed for use by people with mental illness were employed, and information was gathered both from people receiving lithium and their carers. Knowledge of the effects of lithium amongst this group was similar to that found in studies of mentally ill people. There was no significant difference in knowledge according to place of residence (with family, in a community residential facility or in hospital). Most people had a positive attitude to lithium treatment; those with more knowledge had more positive attitudes. People with learning disabilities who are prescribed lithium (and their carers) should receive written information about the effect of the drug. The prescriber should check that sufficient knowledge has been acquired to ensure safety. PMID- 8193455 TI - Environmental and temperament assessments of children with Down's syndrome. AB - This study was designed to investigate the family environment and the temperament of children with Down's syndrome (DS). Parents of 40 children with DS completed the Family Environmental Scale (FES). They also were asked to fill out the Temperament Assessment Battery for Children (TABC) for both the child with DS and the nearest same-sex sibling. A similar questionnaire of the TABC (teacher form) was sent to the children's teachers. The results of these investigations revealed that there were high scores in categories cohesion, expressiveness, achievement, moral/religious emphasis, organization and control on the FES, indicating that family members in the study cohort are relationship oriented, provide support for one another, emphasize ethical values and are able to express their feelings. Comparing TABC results between children with DS with their siblings, significant differences were observed in such categories as adaptability, approach/withdrawal and persistence. Control children were scoring higher in the adaptability and persistence categories, whereas children with DS achieved significantly higher scores than the control children in the approach/withdrawal category. PMID- 8193456 TI - Multi-infarct dementia in Down's syndrome. AB - In spite of a burgeoning literature on the association of Down's syndrome with Alzheimer's disease, the occurrence of multi-infarct dementia has largely been overlooked. A 55-year-old woman with Down's syndrome in whom a dementing process was associated with evidence of significant cerebrovascular disease is reported here. It is considered that she sustained both multi-infarct dementia and probable Alzheimer's disease. It is suggested that such cases are under-reported. PMID- 8193457 TI - The Nordic Conference on Medical Care for Persons with Mental Retardation, Hasselby Castle, Stockholm, Sweden, 3-4 June 1993. PMID- 8193458 TI - Decreased growth hormone response to dexamethasone stimulation test in obese children. AB - Acute administration of glucocorticoids is a recently described stimulus for growth hormone secretion. The aim of the present study was the assessment of dexamethasone-induced growth hormone secretion in obese children. Dexamethasone iv tests were carried out in 14 normal control and 8 obese children. Growth hormone was measured by radioimmunoassay up to 5 h after dexamethasone administration. Dexamethasone elicited clear growth hormone secretion in normal children (mean peak 12.3 +/- 1.6; area under the curve 682.3 +/- 74.3). In the obese children, dexamethasone induced a slight but significant (p < 0.01) increase in growth hormone over basal values. However, the growth hormone response in this group was significantly lower than in the normal controls, when comparing both mean peak (5.5 +/- 2.3, mean +/- SEM) (p < 0.01) and area under the curve (306.8 +/- 44.5) (p < 0.001). PMID- 8193459 TI - Treadmill exercise in Neopolitan children and adolescents. AB - Two hundred and eighty healthy children from Naples, Italy (140 boys and 140 girls) aged 4-17 years were studied using Bruce walking treadmill protocol to voluntary exhaustion. Endurance time and double product increased with age. Systolic blood pressure increased linearly during the test. Multivariate analysis showed that body weight and age were the best predictors of endurance time. Endurance time averaged 15.2 +/- 2.8 min in boys and 13.7 +/- 2.3 min in girls (p = 0.00001). Mean +/- SD double product at peak exercise was 264.3 +/- 63 (boys) and 242 +/- 44 (girls) (p = 0.01). Sinus arrhythmia was present in 78% of the children and disappeared at a mean heart rate of 112 +/- 16 beats/min during exercise. The voltage of the R wave on V4 lead decreased in all but four children during the test (delta R = -0.25 +/- 0.24 mV). The P and T waves increased in almost all children. No ST depression or upward sloping was detected. The voltage of the PR isoelectric line remained constant. The J point was displaced downwards in 78% of children, unchanged in 11% and displaced upwards in the remaining 11% of the children. The present study gives reference parameters for a walking treadmill test in Southern European children. PMID- 8193460 TI - Maximal aerobic power during running and cycling in obese and non-obese children. AB - The maximal aerobic capacity while running and cycling was measured in 22 prepubertal children (mean age +/- SD 9.5 +/- 0.8 years): 14 obese (47.3 +/- 10 kg) and 8 non-obese (31.1 +/- 6.1 kg). Oxygen consumption (VO2) and carbon dioxide production were measured by an open circuit method. Steady state VO2 was determined at different levels of exercise up to the maximal power on the cycloergometer (92 W in obese and 77 W in non-obese subjects) and up to the maximal running speed on the treadmill at a 2% slope (8.3 km/h in obese and 9.0 km/h in lean children). Expressed in absolute values, the VO2max in obese children was significantly higher than in controls (1.55 +/- 0.29 l/min versus 1.23 +/- 0.22 l/min, p < 0.05) for the treadmill test and comparable in the two groups (1.4 +/- 0.2 l/min versus 1.16 +/- 0.2 l/min, ns) for the cycloergometer test. When VO2max was expressed per kg fat free mass, the difference between the two groups disappeared for both tests. These data suggest that obese children had no limitation of maximal aerobic power. Therefore, the magnitude of the workload prescribed when a physical activity program is intended for the therapy of childhood obesity, it should be designed to increase caloric output rather than to improve cardiorespiratory fitness. PMID- 8193461 TI - Viral infections acquired during neonatal intensive care and lung function of preterm infants at follow-up. AB - Respiratory function was assessed at a median postnatal age of seven months in seven infants born prematurely who suffered from chronic lung disease and had a proven viral infection while on the neonatal unit (study group). The results were compared with those of seven infants with chronic lung disease who were gestational age- and gender-matched but who did not have a viral infection (controls). Six of the study group and two controls were symptomatic at follow up. Airways resistance was significantly higher (p < 0.04) and specific conductance significantly lower (p < 0.05) in the study group compared with the controls. We conclude in premature infants with chronic lung disease that viral infections acquired in the neonatal nursery are associated with impaired lung function at follow-up. PMID- 8193462 TI - Munchausen syndrome by proxy: an unexpected cause of severe chronic diarrhoea in a child. AB - A six-year-old boy with severe intermittent diarrhoea was subjected to extensive diagnostic investigation and treatment before the administration of a laxative (sodium sulphate) by his mother was discovered. Early suspicion and analysis of faecal fluid for electrolytes and known laxative substances would have prevented the hazardous clinical course of this case. PMID- 8193463 TI - Aminohydroxypropylidene-biphosphonate in the treatment of bone lesions in a case of Gaucher's disease type 3. AB - Gaucher disease is the most prevalent lysosomal storage disorder. It is characterized by an autosomal recessive inheritance of a deficiency of lysosomal acid glucocerebrosidase. Three clinical phenotypes are recognized: type 1 (non neuronopathic), type 2 (acute neuronopathic), type 3 (subacute neuronopathic). Bone lesions are associated with type 1 and type 3 Gaucher disease. Skeletal involvement is secondary to the progressive accumulation of histiocytes and macrophages laden with glucosylceramide in bone marrow. Our patient was a female type 3 Gaucher patient who was referred to us at the age of 3 years with a neurological symptomatology and severe bone lesions (bilateral fracture of the femur heads, lytic process of the bone matrix of the femurs and distal flask deformity, kyphoskoliosis and chest deformity). The baby was constrained to a wheel-chair. The use of (3-amino-1-hydroxypropylidene)-1,1-biphosphonate (APD) was described in a case of Gaucher disease with very severe bone lesions. We used periodic iv infusions of APD (10 mg every 3 weeks) in our patient for a period of 20 months; after that, enzyme replacement therapy (alglucerase) was commenced. APD treatment showed normalization of bone density, formation of bone callus at the femural heads, positive calcium balance. The urinary Ca/Cr ratio and TRP were consistently normal during therapy. After 9 months of alglucerase therapy the patient was able to walk again. The data indicate that APD therapy can find an indication in Gaucher patients with severe bone involvement. PMID- 8193464 TI - Congenital goiter and secondary hyperlipidemia. PMID- 8193466 TI - Leprechaunism (Donohue's syndrome) described as familial congenital hypertrichosis totalis. PMID- 8193465 TI - Erythropoiesis of very low-birth-weight infants dependent on prenatal growth rate and protein status. AB - This study investigated erythropoiesis in very low-birth-weight infants with special reference to the role of protein status in the regulation of erythropoiesis in 22 appropriate- and 11 small-for-gestational-age infants. Blood samples were drawn at three and six weeks of age. The serum concentrations of erythropoietin, estimated by a solid-phase enzyme immunoassay, were similar in the two groups at both study ages. The total circulating erythrocyte volume and the serum concentration of prealbumin were higher in the appropriate- than in the small-for-gestational-age infants at three and six weeks of age. The former group had a better protein status, although their protein intake was similar or lower. We conclude that erythropoiesis in very low-birth-weight infants is influenced more by protein status and prenatal growth than by serum concentration of erythropoietin. PMID- 8193467 TI - Incidence and prediction of bronchopulmonary dysplasia in a cohort of premature infants. AB - A prospective study on the incidence of bronchopulmonary dysplasia (BPD) in premature infants is reported. A cohort of premature infants with gestational ages < or = 32 weeks, treated during 1989, was followed for one year. Of a total study population of 117 infants, 23 (19.6%) developed BPD, defined as oxygen dependence at 28 postnatal days. However, only 15 infants (12.8%) needed supplementary oxygen at the age of 36 gestational weeks and 5 infants (4.2%) needed supplementary oxygen periodically at one year of age. BPD was found to account for a significant part of both the total and late mortality in the cohort. Measurements of pulmonary mechanics were performed at 3 +/- 1 and 12(13) +/- 1 days of life in a subgroup of 26 infants with RDS who required assisted ventilation for 4 days or longer. No significant difference in lung compliance or resistance could be found during the first examination between infants who later developed BPD and infants with RDS only. At the second examination, infants who later developed BPD had significantly lower lung compliance (0.48 +/- 0.23 ml/cmH2O) than infants in the RDS group (1.50 +/- 0.72 ml/cmH2O) (p < 0.001). Measurements of pulmonary mechanics could be of importance for early prediction of infants at risk of BPD. PMID- 8193468 TI - Aluminum in the neonate related to parenteral nutrition. AB - Sources of aluminium loading and exposure in preterm and full-term newborns were studied. Parenteral nutrition solutions were the main source of aluminium representing 88.7% of total aluminium intake. Blood and urine aluminium levels were followed over a 28-day period in a group of 26 preterm and 9 term infants while receiving parenteral nutrition (duration 15.6 +/- 8.7 days) and later when being formula fed. Urine levels were followed up to 13 weeks in a subgroup of the neonates. Serum aluminium levels (0.86 +/- 0.38 mumol/l) and urine aluminium/creatinine ratio (1.52 +/- 0.81 mumol/mmol) were increased when the infants were receiving parenteral nutrition compared with the control group (p < 0.001). The urine aluminium/creatinine ratio remained high up to 10 weeks following withdrawal of parenteral nutrition and suggested tissular loading. This was confirmed after high aluminium levels were found in post-mortem brain and bone samples from two preterm and one full-term infant. We conclude that both preterm and full-term neonates are susceptible to accumulation of aluminium in tissue while receiving parenteral nutrition. PMID- 8193469 TI - Breast feeding is a natural contraceptive and prevents disease and death in infants, linking infant mortality and birth rates. PMID- 8193470 TI - Significance of measurement of pre-S2 antigen for the prevention of vertical transmission of hepatitis B virus in infants born to HBsAg carrier mothers. AB - The significance of pre-S2 antigen (pre-S2 Ag) as a marker of hepatitis B virus (HBV) infection, especially in infants born to HBsAg carrier mothers who are HBeAg-negative or HBeAg-positive, was evaluated. Pre-S2 Ag was measured by enzyme immunoassay. HBsAg carrier mothers who were HBeAg-negative and HBeAb-positive were divided into two groups: group A, mothers whose infants were not infected with HBV (n = 10) and group B, mothers whose infants were infected with HBV (n = 13). Absorption rates of pre-S2 Ag in group A and B were 0.09 +/- 0.04 and 1.36 +/- 0.95, respectively. The values for pre-S2 Ag in group B were significantly higher than those in group A. Values for pre-S2 Ag among HBsAg carrier mothers who were HBeAg-positive and HBeAb-negative were also measured by reverse passive hemagglutination. In the same way, HBsAg carrier mothers who were HBeAg-positive and HBeAb-negative were divided into two groups: group C, mothers whose infants did not become HBsAg carriers (n = 15) and group D, mothers whose infants became HBsAg carriers (n = 11). The titers of pre-S2 Ag (reverse passive hemagglutination) in group C and D were 2(5.75) +/- 1.68 and 2(10.45 +/- 1.69), respectively. The values for pre-S2 Ag in group D were significantly higher than those in group C. The values for pre-S2 Ag as markers of infectivity became higher with increasing amounts of HBV-DNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193471 TI - Infective endocarditis in newborn infants with structurally normal hearts. AB - Twelve infants with structurally normal hearts were demonstrated to have intracardiac vegetations on echocardiography and diagnosed as having infective endocarditis. All were found in the right side of the heart, most frequently at the junction of the superior vena cava and the right atrium and in no case involved the tricuspid or pulmonary valves. Most were diagnosed in the course of investigation of repeatedly positive blood cultures, despite appropriate antibiotic therapy. Coagulase-negative staphylococci were isolated from blood culture in nine infants, and Streptococcus sanguis and Candida albicans from one each. All infants had had intracardiac central lines inserted to facilitate venous access, either by a percutaneous technique or as a formal surgical procedure. Eight (67%) were successfully treated and made a full recovery. Cardiac murmurs were absent in all of the cases. Echocardiography should be included in the investigation of all neonates with persistently positive blood culture, particularly when intracardiac lines have been sited. Right-sided, non valvar lesions and infection with coagulase-negative staphylococci may carry a better prognosis than previously reported. PMID- 8193472 TI - Is there a role for a twins clinic? An evaluation of parents' responses. AB - To evaluate parental responses to the Twins Clinic, postal questionnaires were sent to the parents of 141 pairs of twins, born outside the maternity hospital who were referred to the clinic in the first three years. The main outcome measures were: the sources of, and reasons for, referral; previous attempts to find help; experiences at the clinic and outcome of the visit. One hundred and thirteen families (80%) replied, of whom 101 (89%) were self-referred. The most common problems for which twins were referred related to behaviour (34) and development (28). In 99 (88%) cases, parents had already sought assistance from other sources (39 from health professionals) but only 29 had found this helpful. In 95 (84%) cases, parents felt there had been a positive outcome from attending the clinic, in the form of reassurance (87), change of management (39), successful support for applications (19) or information (11). Parents' responses indicate that the Twins Clinic meets the needs of families with multiples who are inadequately served by existing sources of help. These will only be improved through education of health professionals (and of the community as a whole) so as to obviate the need for Twins Clinics. PMID- 8193473 TI - Children with early refusal to eat: follow-up during primary school. AB - Twenty-five children, previously investigated at 3-12 months of age for refusal to eat for at least four weeks with no apparent medical cause, have been followed up prospectively with respect to feeding characteristics, general behaviour, somatic health and growth. In the present study, 18 of these children, still resident in Uppsala, were reinvestigated during the primary school period. Comparisons were made with 240 classmates. Information was obtained from school health records and from questionnaires completed by teachers and parents concerning the children's current eating behaviour and general behaviour. Compared with the controls, the children who refused to eat at an early age presented more eating problems both at home (p < 0.01) and at school (p < 0.01), but were not different with respect to general behaviour, somatic health or growth. We conclude that children with previous periods of refusal to eat continue to show problematic eating behaviour, not only at home but also at school. PMID- 8193474 TI - Nicotine and cotinine levels in pericardial fluid in victims of SIDS. AB - We have analyzed the levels of nicotine and cotinine in pericardial fluid in 24 consecutively autopsied cases of sudden unexpected death in infants aged one to six months. Our aim was to determine to what extent victims of sudden infant death may have been exposed to passive smoking near the time of death. Sixteen of the decreased infants were classified as SIDS at autopsy. Other contributing causes of death, predominantly infections, were found in eight cases. Eight infants (30%) had cotinine levels less than 2 ng, indicating that no significant exposure to nicotine had occurred near the time of death. Of the remaining 70%, five had been moderately exposed, seven markedly exposed and four heavily exposed (cotinine levels 2-10 ng, 10-50 ng and more than 50 ng, respectively). Since only 18% of Swedish women smoke after childbearing we conclude that nicotine exposure in infants who died suddenly was much higher than one would otherwise expect. It is hypothesized that high concentrations of nicotine and nicotine metabolites around the heart may affect cardiac function and thus play a role in the mechanisms causing SIDS or other categories of sudden unexpected death. PMID- 8193475 TI - Clinical criteria for estimating recovery from childhood bacterial meningitis. AB - A comparison study was conducted between 105 children (aged 3 months to 15 years) who had recovered from bacterial meningitis uneventfully and 29 children who had suffered from subsequent neurological complications or sequelae. The objective was to find a potential correlation between easily measurable clinical variables and the risk of developing neurological complications. Sixteen clinical signs and measurements routinely registered in patients with bacterial meningitis were recorded daily during the first 14 days of hospitalization. Differences found between the two groups were mean morning temperature, presence of neck rigidity and willingness to leave the supine position. The results indicate that if a child recovering from bacterial meningitis continues to be feverish, has neck rigidity, or is reluctant to leave the supine position over seven days, she/he runs a special risk of developing neurological complications or sequelae, which should be actively sought for using all available measures. PMID- 8193476 TI - An epidemiological study of Hirschsprung's disease and additional anomalies. AB - The incidence of Hirschsprung's disease was studied in approximately 1.5 million consecutive live births in Denmark by hospital records. A diagnosis of Hirschsprung's disease required a histologic verified absence of ganglion cells in either biopsy or surgical colonic specimens. The incidence of Hirschsprung's disease was found to be 0.140 per 1000 live births (1:7,165) with a male: female ratio of 4.1:1 in short segment, and 2.4:1 in long segment Hirschsprung's disease (p = 0.36). Maternal age and birth order were unimportant factors. The association of Hirschsprung's disease and Down's syndrome was seen in 9 of the 207 patients and may represent a real association, whereas the association with congenital heart defects seen in 2% (not including patients with Down's syndrome) is more doubtful. A mortality of 16% among the patients with Hirschsprung's disease emphasizes the extreme importance of early diagnosis. PMID- 8193477 TI - Cells, bilirubin and light: formation of bilirubin photoproducts and cellular damage at defined wavelengths. AB - Cultured cells from one human and one murine cell line were treated with bilirubin and irradiated with visible light of different wavelengths, either from phototherapy lamps or from a Xenon/Mercury lamp equipped with a monochromator. Bilirubin bound to human serum albumin was also irradiated with light. After irradiation, the bilirubin and its photoisomers were extracted and analysed with High Pressure Liquid Chromatography. The formation of single strand breaks in the DNA of treated cells was studied using a fluorescence marker. Cytotoxicity in the mouse skin cell line was measured by loss of the ability to form visible colonies in vitro. Green light exposure favours the production of lumirubin, while blue light causes more DNA damage and cytotoxicity. Green light may be more efficient and safer than shorter wavelength exposure when treating jaundiced newborns with phototherapy. PMID- 8193478 TI - Diabetes mellitus in Danish cystic fibrosis patients: prevalence and late diabetic complications. AB - The prevalences of impaired glucose tolerance (IGT), diabetes mellitus and late diabetic complications were studied in all Danish cystic fibrosis (CF) patients. A total of 311 CF patients were identified with an estimated ascertainment rate above 98%. Glucose tolerance was classified in 278 (89%) patients: the prevalences of IGT and diabetes mellitus were 13.7% (38 patients) and 14.7% (41 patients), respectively, with no sex differences. The prevalence of diabetes mellitus increased with age but not with the severity of CF as compared with age- and sex-matched non-diabetic CF patients. Diabetes was diagnosed at a median age of 20 years (range 3-40 years) and the duration of diabetes was 1.7 years (0.1-17 years). Twenty-eight of the diabetic patients (70%) were treated with insulin, on average 20 (4-90) IU per day. Late diabetic complications were identified in 4 patients (10%) with a duration of diabetes mellitus of 1-17 years: background retinopathy (2 patients), diabetic nephropathy (1 patient), microalbuminuria (1 patient) and neuropathy (2 patients). Thus diabetic CF patients are probably not less prone to develop late diabetic complications than patients with other types of diabetes of equally long duration and comparable glycemic control. PMID- 8193479 TI - Outcome of cadaver kidney transplantation in small children. AB - Small children have often been reported to have poor outcome after kidney transplantation (KT). Recent reports from North America have shown that the use of living-related donors improves patient and graft survival. We report the experience in one centre of primary cadaveric KT using sequential immunosuppression in nine children aged 8-30 months and weighing 5.4-9.8 kg; donors were 0.7-12.3 years old. Four patients had pre-emptive KT and the other five were on peritoneal dialysis; the mean +/- SD waiting time was 2.0 +/- 2.4 months. Perioperative care has been published previously. The surgical approach was intraperitoneal if the aorta and vena cava were used (n = 7) and extraperitoneal for common iliac vessels anastomosis (n = 2); the duration of surgery was 3.5 +/- 0.9 h and the time for vascular anastomosis was 32 +/- 6 min. The recipients received ATG, azathioprine, prednisone and delayed administration of cyclosporin A. The patients were followed for 12-98 (median 41) months and showed good graft function (inulin clearance 63-100 ml/min/1.73 m2); only one child with recurrent haemolytic uraemic syndrome lost his graft three months post transplantation and died after he had received a second graft. None of the recipients required post-transplant dialysis; arterial hypertension involved four children and was related to graft artery stenosis in two. Growth improved by 0.24 +/- 0.48 SD score of height per year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193480 TI - Inhibitor to factor V after exposure to fibrin sealant during cardiac surgery in a two-year-old child. AB - A two-year-old infant developed an inhibitor to factor V after cardiac surgery, with application of fibrin sealant containing bovine thrombin. Investigation of this inhibitor by means of inhibition experiments and immunoblot analysis revealed that the inhibitor reacted strongly with bovine, but only weakly with human factor V. Plasmapheresis proved effective in increasing factor V levels. This patient provides further evidence that exposure to topical thrombin preparations may lead to the development of inhibitors in the postoperative period that may cause bleeding complications. PMID- 8193481 TI - Interpretation of random urinary catecholamines and their metabolites in neuroblastoma. AB - This study reports experience in the estimation of urinary catecholamines (uCATs) and their metabolites in the diagnosis and follow-up of neuroblastoma. Random urine samples were assayed for dopamine, noradrenaline and adrenaline, together with their metabolites 4-hydroxy 3-methoxymandelic acid (HMMA) and homovanillic acid (HVA), using HPLC with electrochemical detection. Twenty of 21 patients had elevation of one or more uCATs metabolites at diagnosis. Patients were monitored serially from diagnosis and, in those patients who had delayed resection of primary tumour (n = 13), particular attention was paid to levels at the pre surgical evaluation as an indicator of persistence of viable disease at the time of surgery; dopamine proved to be the most accurate indicator of persistent disease at this time. Five of these patients developed recurrent disease, 4 of whom had elevation of two or more uCATs metabolites at the time of relapse. Several conclusions can be drawn from this study: (a) results for HMMA, HVA and dopamine in random urine samples will detect all but the most biochemically immature or inert tumours; (b) dopamine may be the most reliable indicator of persistent disease and (c) noradrenaline and adrenaline measurements were of little benefit. As results are expressed in relation to urinary creatinine, excretion of which may be affected by dietary protein and is therefore not constant, borderline results should be repeated. PMID- 8193482 TI - Multisystem triglyceride storage disorder without ichthyosis in two siblings. AB - A four-year-old boy presented with hepatomegaly, vacuolized granulocytes (Jordans' anomaly) and slightly progressive myopathy as signs of multisystem triglyceride storage disease. The nine-year-old sister of the patient also showed Jordans' anomaly and early fatigability, but no overt weakness. Biochemical analysis revealed normal values for carnitines, carnitine palmityl transferase in serum and striated muscle, and beta-oxidation enzymes in striated muscles. Distribution of non-membrane-bound lipids in granulocytes, fibroblasts, smooth muscle cells and striated muscle was compatible with Chanarin-Dorfman syndrome. In contrast to Chanarin-Dorfman syndrome, our patients lacked congenital ichthyosis. PMID- 8193483 TI - Neonatal polycythemia and maternal hypertension. PMID- 8193484 TI - X-linked agammaglobulinemia, growth hormone deficiency and delay of growth and puberty. AB - Coinheritance of X-linked agammaglobulinemia and growth hormone deficiency (XLA/GHD) has been classified as an independent primary immune deficiency. We evaluated the pattern of growth and endocrine function in seven XLA subjects (ages 10.9-20.1 years); four belonged to two different XLA pedigrees and three represented sporadic XLA cases. Three had reached adulthood (final stature 176.0, 173.5 and 165.0 cm, respectively) and their retrospective growth showed delay in growth and puberty during adolescence. In the other four subjects, growth hormone production was measured by growth hormone pharmacological stimulation tests (clonidine, arginine): three of four patients had insufficient growth hormone responses (peak growth hormone < 10 micrograms/l); all three had delayed puberty; their growth hormone responses increased after "priming" with testosterone, reaching values > 10 micrograms/l in two of them and allowing diagnosis of "true" growth hormone deficiency in the third. The fourth was a normally growing subject who showed a normal growth hormone response both before and after testosterone priming. Six out of the seven subjects showed a growth pattern consistent with delay in growth and puberty. Our results suggest that true XLA/GHD is rarer than previously supposed and that subnormal responses to growth hormone stimulation tests may be found without sex steroid priming of the test in adolescence. The most probable growth pattern in XLA appears to be delay in growth and puberty, as has already been described for other chronic diseases. PMID- 8193485 TI - Plasma amino acid and protein concentrations in infants fed human milk or a whey protein hydrolysate formula during the first month of life. AB - The aim of the study was to compare growth parameters, biochemical indices of protein metabolism and plasma amino acid concentrations in infants fed either human milk (n = 12) or a whey protein hydrolysate formula (n = 13) during the first month of life. Growth and gain in skin fold thickness were similar in both groups whereas serum protein concentration was significantly decreased (57.4 +/- 3.9 versus 61.2 +/- 2.9 g/l) in the infants fed the whey hydrolysate formula. The discrepancies between the plasma amino acid pattern of the whey hydrolysate formula group and that of the human milk group lessened during the first month. Nevertheless, at a mean age of 33 days the plasma threonine concentration remained twice as high and the plasma tyrosine, phenylalanine and proline concentrations were significantly lower in the whey hydrolysate formula group than in the human milk group. Thus, compared with breast-fed infants, growth and most of the biological indices of protein metabolism were satisfactory in infants fed during the first month of life on a whey protein hydrolysate formula. Nevertheless, the decrease in total plasma protein concentration needs to be confirmed in a larger cohort of infants. In addition, further research is necessary to investigate the possible ways of reducing the hyperthreoninemia and preventing other plasma amino acid disturbances since it would be desirable to obtain plasma amino acid levels similar to those of breast-fed infants. PMID- 8193486 TI - Lipidic and fatty acid status in treated hyperphenylalaninemic children. PMID- 8193487 TI - Neonatal plasma vitamin K1 levels following oral and intramuscular administration of vitamin K1. AB - Vitamin K1 levels were measured by high performance liquid chromatography in cord blood (n = 33) and at the age of 97-120 h after administration of 2 mg of vitamin K1 orally (n = 88) or 1 mg of vitamin K1 by im injection (n = 88). Vitamin K1 levels were less than 0.05 micrograms/l in cord blood. The mean (range), SEM, mode and median values (micrograms/l) for the infants given oral vitamin K1 were 17.99 (1-56), 1.25, 8 and 15.5 and those for the infants given im vitamin K1 15.83 (2-57), 1.01, 11 and 14, respectively. The t-test showed no significant difference in the mean values (p = 0.09) in the infants given oral or im vitamin K. PMID- 8193488 TI - High-dose versus low-dose bovine surfactant treatment in very premature infants. AB - The aim of the study was to determine if high-dose bovine surfactant (Alveofact, initially 100 mg/kg birth weight) would improve oxygenation compared with low dose surfactant (50 mg/kg birth weight) administered intratracheally within 1 h after birth. Inclusion criteria included gestational age 24-29 weeks and birth weight 500-1500 g, intubation and mechanical ventilation, absence of congenital malformations and bacterial infections. Retreatment was considered if the fraction of inspired oxygen (FiO2) was > 0.4 (dose 50 mg/kg birth weight). The primary endpoint was level of oxygenation (PaO2/FiO2) 2 h after treatment. The study design was a sequential analysis using a triangular test with alpha = 0.05 and 95% power to detect a 25% improvement in the endpoint. Oxygenation was improved significantly with high-dose (n = 42) compared to low-dose treatment (n = 48): 30.9 +/- 15.0 kPa (231.5 +/- 112.7 mmHg) versus 24.1 +/- 15.7 kPa (180.6 +/- 118.0 mmHg) (mean +/- SD). The survival rate was 83% in both groups and the incidence of pulmonary interstitial emphysema was 33% versus 14% with the high dose treatment. We conclude that high-dose surfactant significantly improved oxygenation and reduced lung barotrauma. An initial dose greater than 50 mg/kg birth weight of surfactant is required for optimal acute response. PMID- 8193489 TI - Haemolytic uraemic syndrome and unpasteurized milk. PMID- 8193490 TI - Oropharyngeal and esophageal pressure during mono- and binasal CPAP in neonates. AB - Oropharyngeal and esophageal pressures were measured via a tip-transducer during mono- and binasal CPAP in 30 neonates. During nasal CPAP, increasing flows are followed by an increase in oropharyngeal pressure, although there were great variations among the pressures recorded. On the other hand, no increase in the esophageal pressure could be registered during nasal CPAP. It is advisable to use the lowest flow which ameliorates the respiratory status in neonates. To achieve an appropriate pressure in the oropharynx it is advisable to close the mouth during nasal CPAP in the neonate. PMID- 8193491 TI - Hepatocellular carcinoma. PMID- 8193492 TI - Physiological changes, plasma beta-endorphin and cortisol responses to tracheal intubation in neonates. AB - Physiological, plasma beta-endorphin and cortisol responses to nasotracheal intubation were studied in 20 distressed infants of median age 0.3 days (range 0.1-23 days) randomized into groups given pethidine 1 mg/kg (n = 10) or alfentanil 20 micrograms/kg plus suxamethonium 1.5 mg/kg (n = 10) before intubation. All of the infants were given glycopyrrolate 3-5 micrograms/kg. Hypoxaemia during intubation was found in all 10 infants in the pethidine group and in 7 of 10 infants in the alfentanil-suxamethonium group, its duration being significantly longer in the pethidine group and being associated with the duration of the intubation procedure. Blood pressure increased, but not statistically significantly, in all except 2 patients in the alfentanil suxamethonium group and bradycardia appeared in 1 patient in each group. Plasma beta-endorphin and cortisol values did not show any statistically significant intra-group or inter-group differences. Newborn infants suffer from hypoxaemia during intubation when awake more and therefore need adequate premedication before elective intubation. One alternative is the combination of glycopyrrolate, alfentanil and suxamethonium described here, although the ideal medication and dosage still remain to be defined. PMID- 8193493 TI - Prediction of respiratory morbidity in the third year of life in children born prematurely. AB - We have tested the hypothesis that recurrent respiratory symptoms in the third year of life in patients born prematurely were more likely to reflect a family history of atopy rather than adverse neonatal events. Comparison of 28 symptomatic and 72 asymptomatic children revealed that a family history of atopy (p < 0.01), prolonged dependence on respiratory support in the neonatal period (p < 0.01) and extreme immaturity (p < 0.02) were significantly commoner in the symptomatic group. The relative risk of having symptoms was 2.27 for a family history of atopy, 2.48 for prolonged dependence on respiratory support and 1.7 for low gestational age. We conclude that respiratory morbidity in the third year of life following premature delivery has a multifactorial aetiology. PMID- 8193494 TI - The role of aluminium for adverse reactions and immunogenicity of diphtheria tetanus booster vaccine. AB - In a randomized, double-blind clinical trial, 235 schoolchildren aged 10 years received either a regular, aluminium-adsorbed diphtheria-tetanus vaccine or the same vaccine in fluid form, in order to investigate if local side effects could be diminished by exclusion of aluminium. System reactions were rare and local reactions frequent in both groups but larger local reactions were even more pronounced in the non-adsorbed vaccine group. Antibody responses to both vaccines were excellent and even slightly higher to the non-adsorbed diphtheria-tetanus vaccine (p = 0.0135 and 0.0014 for anti-diphtheria and anti-tetanus, respectively). This study has shown that fluid diphtheria-tetanus vaccine does not solve the problem of extensive local side effects induced by the diphtheria tetanus school booster. Alternative strategies, such as changes in vaccine composition, dosage and spacing, will have to be considered. PMID- 8193495 TI - Immunosuppression after measles vaccination. AB - The influence of conventional live attenuated measles vaccine on cellular immune responsiveness was investigated in Sweden and Guinea-Bissau. Sixteen children in a residential area in Bissau and 16 living in southern Stockholm were examined before and 8-10 days after vaccination. Lymphoproliferation was measured to concanavalin A (con-A), PPD and tetanus toxoid (TT) using a whole-blood 3H thymidine incorporation assay. Stimulation indices were significantly lower after vaccination than before, in the case of con-A (p = 0.03) and TT (p = 0.01) in the Guinean children and in the case of PPD (p = 0.009) and TT (p = 0.03) in the Swedish children. Stimulation of lymphocytes from measles-immune children with measles antigens resulted in weak lymphoproliferative responses. These observations may be relevant to the increased mortality found in children immunized with high-titre measles vaccines, as compared to controls, in recent studies. The study confirms the applicability and usefulness under field conditions of the whole blood version of the thymidine incorporation assay. PMID- 8193496 TI - Chlamydial etiology of acute lower respiratory tract infections in children in the Sudan. AB - The role of Chlamydia pneumoniae in 110 Sudanese children with signs of acute lower respiratory tract infections (ALRI) was investigated. Four (3.6%) had evidence of C. pneumoniae infection, of whom 3 were culture-positive, while 1 had an antibody response suggesting a recent infection. IgG antibodies at a titer of > or = 1:32 to C. pneumoniae, Chlamydia psittaci and Chlamydia trachomatis were detected in 27 (24.5%), 27 (24.5%) and 7 (6.4%) of the 110 ALRI cases, respectively. C. pneumoniae, C. trachomatis or C. psittaci were not detected in nasopharyngeal secretions from any of 110 patients when fluorescence-labeled specific monoclonal antibodies were used. In a seroepidemiological survey, 318 healthy Sudanese persons aged between 1 month and 67 years were studied for C. pneumoniae antibodies. PMID- 8193497 TI - Ten years after acquiring an HIV-1 infection: a study in a cohort of eleven neonates infected by aliquots from a single plasma donation. AB - We present data from a 10-year follow-up study of 11 children who had been infected in the neonatal period by small aliquots of plasma from a single donation. Three of the children died within the first 2.5 years of life, 5 other children died between 6.2 and 11 years after infection and 3 are alive at present. The latter children are classified as P1B (asymptomatic), P2A (non specific findings) and P2B (neurological changes). All infected children showed progressive decline of cellular immunity. Immunoglobulin levels in serum were increased in the majority of children for prolonged periods and homogeneous immunoglobulin components were present. The severity of the disease was related neither to the clinical condition of the infants in the neonatal period nor to the volume of transfused plasma, the interval between freezing and thawing of the plasma, gestational age at birth and age at transfusion. Coinciding infections with other viruses had no impact on disease progression during the follow-up period of 10 years. PMID- 8193498 TI - Standardizing the assessment of diarrhea in clinical trials: results of an interobserver agreement study. AB - Interobserver agreement was determined between nurses and parents using a standard method of assessing diarrheal stools. The study population consisted of patients less than three years of age hospitalized at The Hospital for Sick Children, Toronto, Canada. Stool samples were independently categorized by observer pairs within minutes of being obtained from children with and without diarrhea as: watery--liquid, no solid elements; loose--liquid with solid elements; pasty--like a paste; formed--normal solid. Watery and loose stools were regarded as abnormal and indicative of diarrhea. Teaching sessions were conducted for nursing shifts, while parents were instructed prior to each observation. In the nurses' agreement study, each stool specimen was examined by the nurse providing care to the patient from whom the stool was obtained and a nurse not looking after the patient. Parents' assessments were also compared with nurses' assessments. Finally, parents' assessments were compared with each other. In the first group, agreement beyond chance for presence or absence of diarrhea measured by kappa was 0.78 (95% confidence intervals (CI) 0.55-1.0). The observed agreement on 148 pairs of observations between parents and nurses was 75% (kappa = 0.5; 95% CI 0.36-0.64). Between-parent agreement on 30 other paired observations was 77% (kappa = 0.54; 95% CI 0.24-0.84). Teaching parents about the four categories is a potentially useful adjunct for assessment of diarrheal stools in children. PMID- 8193499 TI - Cow's milk versus soy-based formula in mild and moderate diarrhea: a randomized, controlled trial. AB - We determined the efficacy of a soy-based formula compared with a cow's milk formula in infant refeeding after acute diarrhea in a randomized controlled double-blind clinical trial. Infants 2-12 months of age with diarrhea of less than one week's duration and mild or moderate dehydration admitted to a pediatric hospital or in the practice of a participating primary care pediatrician were investigated. Seventy-six patients were enrolled and 73 completed the study; 39 infants received a soy-based formula (Isomil) and 34 received a cow's milk formula (SMA). Hospitalized patients were rehydrated with an oral glucose electrolyte solution or an iv dextrose-sodium solution. Outpatients received oral glucose-electrolyte solution. In all patients, the study formula was commenced ad libitum during the first 24 h as determined by the attending pediatrician. The primary outcome measure was duration of diarrhea, defined as time to first normal stool, when subsequent stools were normal for a 24-h period. In addition, a predetermined secondary outcome was proportion of treatment failures, defined as the need to reinstitute clear fluids because of emesis, refusal to accept study formula, need for iv fluids due to negative fluid balance or diarrhea persisting beyond 7 days after enrollment. Total duration of diarrhea was significantly longer (p = 0.03) in those receiving cow's milk (mean +/- SD 6.6 +/- 4.2 days) than in those receiving soy-based formula (4.5 +/- 3.6 days). Volume of formula intake and weight gain at 14 days were not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193500 TI - Effect of dietary nucleotide supplementation on diarrhoeal disease in infants. AB - The effects of a nucleotide-supplemented formula on diarrhoeal disease was studied in 141 infants (group 1) who belonged to the low socioeconomic stratum; 148 controls (group 2) received the same formula but unsupplemented. Group 1 experienced less episodes of diarrhoea (109 versus 140), including less first episodes (74 versus 102; chi-square = 8.19, p < 0.004; odds ratio 2.01) and for a lesser number of days (807 versus 996 days); 45.0% and 31.1% of infants in groups 1 and 2, respectively, never developed episodes of diarrhoea. There were no differences in the clinical characteristics of the episodes or in the enteropathogens isolated from symptomatic or asymptomatic infants. The mechanisms through which nucleotides decrease the incidence of diarrhoeal disease in infants remain unclear. PMID- 8193501 TI - Normal weight for length in newborn infants in whom growth hormone deficiency was later diagnosed. Swedish Paediatric Study Group for GH Treatment. AB - A new model for evaluating leanness/fatness (LeanSDS) in the newborn infant has been used to examine body weight for length in a group of Swedish infants in whom idiopathic growth hormone deficiency (GHD n = 220) was later diagnosed. These infants have earlier been reported to be significantly shorter (median = -0.87 SDS; SDS; standard deviation scores) and lighter (median = -0.60 SDS) in relation to gestational age, than the most recent reference. A group of infants who later developed GHD due to organic etiologies (n = 92) had normal weight and length for gestational age at birth. Using the LeanSDS model (with intercept 0.0 and regression coefficient 0.7) revealed that these idiopathic GHD infants have weight that is normal for their length (mean LeanSDS = 0.11 +/- 0.08 (SEM); n.s.) why the abnormality is a reduced linear growth. These findings also indicate that birth length (linear growth) should be given increased attention when size at birth is evaluated. PMID- 8193502 TI - Impaired growth in children with asthma during treatment with conventional doses of inhaled corticosteroids. AB - We describe 6 (4F, 2M) prepubertal children with moderate asthma diagnosed at a mean age of 2.8 years. All patients were treated with inhaled corticosteroids in a dose of between 300 and 800 mcg of beclomethasone dipropionate (becotide) daily, given either as an aerosol or rotahaler. Mean height velocity SDS decreased from -0.8 (range +0.5 to -2.0) to -3.2 (range -1.3 to -4.8) when the dose was increased. Alternatively, when the dose was reduced or stopped, mean height velocity SDS increased from -3.2 (range -2.0 to -4.8) to +0.8 (range -1.2 to +2.7). Careful assessment of height velocity is indicated in all children receiving treatment with inhaled corticosteroids. PMID- 8193503 TI - Right-sided valvular regurgitation in normal children determined by combined colour-coded and continuous-wave Doppler echocardiography. AB - Using Doppler echocardiography, the prevalence of tricuspid and pulmonary valve regurgitation was determined prospectively in 173 normal children, aged 8.3 +/- 2.7 (range 5-14) years. Pulmonary regurgitation was defined as a red-yellow or mosaic coloured regurgitant flow, continuing to end-diastole with continuous-wave Doppler. It was found in 84% of the children. Tricuspid regurgitation was defined as a blue-green or mosaic coloured regurgitant flow from the tricuspid valve into the right atrium lasting > 0.5 systole, as determined by continuous-wave Doppler. Tricuspid regurgitation was present in only 8% of the children. Tricuspid regurgitation flow of very short duration, considered to be due to valve closure, was found in 75%. No effect of age, presence of a vibratory innocent heart murmur or gender on the prevalence of right-sided valvular regurgitation could be demonstrated. All regurgitations were haemodynamically insignificant. Thus right sided valvular regurgitation in normal schoolchildren is a normal physiological finding with relatively high prevalence. In the absence of functional reasons for these regurgitations and in the absence of structural pulmonary or tricuspid valve disease, these signals should be considered physiological in order to avoid iatrogenic heart disease. PMID- 8193504 TI - Computerized cry analysis in infants affected by severe protein energy malnutrition. AB - A new method of computerized cry analysis has been utilized to evaluate the cries of infants affected by severe protein energy malnutrition. We studied 17 Kenian babies affected by severe malnutrition for more than four months (9 cases of marasmus and 8 of kwashiorkor) and a control group of 17 well-nourished babies. The cries of the malnourished children showed lower inter-utterance variability, formants' frequencies and cry score, assigned by the Infant Cry Modulation Assessment Scale. The melodic pattern was more often flat, rising or falling rising, when compared to the cries of the well-nourished babies. We hypothesize that these differences reflect the state of brain damage associated with protein energy malnutrition. No differences were found between the cries of infants affected by marasmus and those affected by kwashiorkor, between the cries recorded before and after nutritional therapy and between the first cries of malnourished children who subsequently died during hospitalization and those of infants who survived. PMID- 8193505 TI - Epidemiology and prevention of caustic ingestion in children. AB - A total of 102 children less than 16 years of age admitted for caustic ingestion in the period 1976-1991 were registered. The annual incidence rate of hospitalization was 10.8:100,000 for the city of Aarhus, Denmark. Esophageal burns occurred with a frequency of 5.0:100,000 per year. Ninety-four percent of the children were less than 5 years old. For this age group, the incidence rates of admission and esophageal burns were 34.6:100,000 and 15.8:100,000, respectively. All ingestions were accidental. The incidence rates of esophageal burns in children 0-4 years old (p = 0.019) decreased significantly during the period studied. The cause of this decrease is not clear, but a change in the spectrum of household products and the gradual introduction of child-proof caps are possible explanations. To minimize the frequency of accidents, an information campaign directed specifically at parents of toddlers is recommended. Information material should stress that caustics should always be inaccessible to children and stored separately, and should never be decanted. PMID- 8193506 TI - A psychosocial follow-up of ten adolescents with low anorectal malformation. AB - Ten adolescents, aged 12-16 (mean 14.5) years, with corrected low anorectal anomalies were assessed with regard to somatic condition, psychopathology and psychosocial functioning by semistructured interviews and questionnaires. Half of the patients still had a persistent dysfunction involving problems with constipation and/or soiling. Six of 10 adolescents met the criteria for a psychiatric diagnosis and had scores indicating mild to severe impairment of psychosocial function. Psychosocial functioning was correlated with chronic family difficulties. The findings are in contrast to previous studies and reveal hidden problems and unmet social needs. To optimize their mental health and psychosocial functioning, children with low anorectal anomalies need both somatic and psychosocial follow-up. PMID- 8193507 TI - Dietary modifications versus dicyclomine hydrochloride in the treatment of severe infantile colics. AB - This study examined 120 infants, aged 3-12 weeks, with severe colics and compared the results of a specific hypoallergenic diet (group A) with those of pharmacological treatment (group B). Non-breast-fed group A infants received soy milk and if unresponsive, hydrolyzed milk formulas; mothers of breast-fed infants received a diet without cow's milk, eggs or fish. Breast-fed and non-breast-fed group B infants received dicyclomine hydrochloride 3 mg/kg/day. Results, based on quantitative measurements of crying, indicated that in breast-fed infants there was no significant improvement between group A (62.5%) and group B (66.6%) infants. Among formula-fed infants, comparison of positive results using soy milk (65.9%) with positive results using dicyclomine (53.3%) was not significant; positive results using soy milk and hydrolyzed milk formulas in non-responders to soy milk, provided an improvement in 95.4% of cases. Pharmacological treatment provided an improvement in 53.3% of cases. The difference was significant (p < 0.01). PMID- 8193508 TI - Study on coagulase-negative staphylococcal septicemia in Chinese low-birth-weight infants. PMID- 8193509 TI - Allergy in early and late onset of atopic dermatitis. PMID- 8193510 TI - Influence of MPR revaccination on tuberculin and sensitin skin reactions in children. AB - Many viral diseases, as well as viral vaccines, have a transient effect in depressing cell-mediated immunity. The study group consisted of 52 children, aged 6.0-6.3 years. Thirty (57%) of them had been revaccinated against measles, parotitis and rubella (MPR vaccination). In MPR-revaccinated children, the mean skin reaction sizes were 4.7 mm, 4.1 mm, 4.3 mm and 2.1 mm to tuberculin, Mycobacterium avium, M. scrofulaceum and M. fortuitum sensitins, respectively. In non-revaccinated children (n = 22), the respective mean skin reaction sizes were 3.0 mm, 2.8 mm, 2.9 mm and 0.8 mm. The difference between re- and non revaccinated children was statistically significant with regard to reactions to M. fortuitum sensitin (p < 0.05). These results suggest that the influence of viral revaccination is different from natural infection or primary vaccination. The mechanism of stimulation of cell-mediated immunity--either specific or non specific--is unknown. PMID- 8193511 TI - Vascular complications in adult patients after orthotopic liver transplantation: role of color duplex sonography in the diagnosis and management of vascular complications. AB - Vascular complications after orthotopic liver transplantation are one of the most serious problems in liver-grafted patients, and if undetected they may result in graft failure and death unless prompt revascularization or retransplantation is performed. As the outcome of treatment of vascular complications depends on an early diagnosis, the role of color-coded duplex sonography (CCD) for diagnosis and treatment was analyzed during a 17-month observation period. Altogether, 88 consecutive liver allografts in 77 adult patients were studied by serial CCD. Vascular complications occurred with an incidence of 12.9%. Hepatic artery complications represented the most frequent event with an incidence of 11.6%. CCD showed a sensitivity of 100%, a specificity of 97% and a positive predictive value of 0.84. With the use of CCD, vasculature and localization of the site of arterial complications can be directly visualized and the various types of complications can be differentiated, thus reducing the time needed for diagnosis. Early hepatic artery complications, occurring during the first 3 days after transplantation, which were immediately diagnosed by CCD examination and rapidly treated by revascularization had a good clinical outcome. In contrast, the outcome of vascular complications requiring retransplantation was found to be poor. As radiologic intervention offers an alternative to the treatment strategy of vascular complications in liver-grafted patients, CCD is the method of choice to noninvasively monitor the initial and follow-up examinations after intervention. PMID- 8193512 TI - Differential diagnosis in variants or abnormalities of the hip on MRI. AB - In the differential diagnosis of unspecific hip pain MRI becomes increasingly important. In particular it is useful in the diagnosis of avascular necrosis, primary and secondary bone tumors, osteomyelitis and synovial processes. According to the higher frequence of MR examinations of the hip the number of nonpathological incidental findings is rising. 39 'pitfalls' and abnormalities were found on MRI of 152 patients with unspecific hip pain. Soft tissue penetrating cortical lesions of the femoral neck (herniation pit, n = 4), physiological changes of bone marrow, synovial proliferation (n = 6) of the hip joint capsule, epiphyseal scars of the femoral head (n = 12) and the transient osteoporosis (n = 12) are some of the morphological changes of the hip, which may cause difficulties and misinterpretations on MRI of the hip. Knowledge of their radiological characteristics on MRI is important, especially in cases of unspecific hip pain. PMID- 8193513 TI - Sonographic technique in diagnosis of urethral strictures in men. AB - Sixteen male patients were examined by sonography, urethrography and urethroscopy because of a clinical suspicion of urethral stricture. For sonography the urethra was filled with anesthetic gel using an inflexible plastic syringe. Ten strictures were identified by urethroscopy; 9 of them were also seen in urethrography and 5 in sonography. All the membrane-like strictures (4), and 1 very proximal stricture remained unvisualized in sonography. Sonography revealed also 1 diverticulum and 1 posttraumatic fistula, which were also seen in urethrography. The presented sonographic method for visualizing the male urethra proved to be useful. PMID- 8193514 TI - Perfusion scintigraphy and color-coded duplex sonography in a minimally perfused renal allograft. AB - Both, 99mTc DTPA perfusion scintigraphy and color-coded duplex sonography are reliable methods to quantitatively and qualitatively assess kidney transplant perfusion. In this case, minimal perfusion could be detected in a kidney allograft with marked vascular rejection by the scintigraphic analogous scan, whereas color-coded duplex sonography failed. PMID- 8193515 TI - Transvenous and intra-arterial ultrasound monitoring of laser-assisted angioplasty. AB - To evaluate the effects of peripheral laser angioplasty in vivo, two new applications of intravascular ultrasound have been tested. Sonography of iliac and femoropopliteal arteries using 6.2-French/20-MHz transducers via a transvenous approach was technical feasible, however, spatial resolution of images was not equivalent to intra-arterial sonography. Catheters and guide wires could be observed in normal and moderate stenotic segments but not in occlusions. Using a combined 9-French multifiber-laser-ultrasound-catheter sonographic analysis of arterial stenoses revealed a reduction of the degree of stenoses from 84 +/- 8% before to 47 +/- 10% after laser angioplasty. Both imaging modalities detected bright echoes during pulsed laser energy delivery with a focal appearance within the occlusion material and a diffuse pattern involving the distal arterial lumen. Probably these effects are caused by optico-mechanical plaque disruptions and ejections of gaseous products during the laser ablation. Further development of combined catheter devices to guide energy delivery by continuous imaging might improve the results of laser angioplasty. PMID- 8193516 TI - Spontaneous splenic rupture in acute myeloid leukemia: sonographic follow-up study. AB - We report on a 52-year-old patient with acute myeloid leukemia. After induction chemotherapy, routine ultrasound displayed a round focal hyperechoic intrasplenic lesion. Tumor was primarily misdiagnosed for splenic hemangioma. Diagnosis of spontaneous progredient splenic rupture was made by color-coded Doppler sonography, sonographic follow-up examinations and confirmed by splenectomy for final treatment. No trauma was found. PMID- 8193517 TI - Two different manifestations of botryoid sarcoma (embryonal rhabdomyosarcoma) of the biliary tree. AB - A 16-month-old girl and a 5-year-old boy with botryoid sarcoma of the biliary tree are presented. The girl's tumor infiltrated the liver, whereas the boy's tumor was confined to the extrahepatic biliary tree. Computed tomography not only enabled the evaluation of the tumor-surrounding structures, but also indicated the tumorous nature of the lesion following intravenous administration of a contrast agent. In cholangiograms, the exact extension of the intraluminal tumors could be differentiated by the typical bizarre filling defects. PMID- 8193518 TI - Unilocular toxoplasmosis simulating intracerebral tumor. AB - Toxoplasmosis is a common infection with increased incidence in patients suffering from AIDS. In this paper we report a rare case of toxoplasmosis without evidence of AIDS: The patient had a singular tumor-like lesion in the right parietal lobe in CT and MRI. In neurosurgical intervention no tumor was found. Finally, different histopathological examinations led to the diagnosis of toxoplasmosis. Diagnostic and therapeutic regimes in patients with suspect tumor like lesions should be discussed. PMID- 8193519 TI - [Progress in magnetic resonance tomography of the liver: value of ultra-rapid imaging and liver-specific contrast media]. AB - Ongoing technical improvements in magnetic resonance imaging (MRI) and the development of liver-specific contrast agents are likely to have an impact on the clinical assessment of liver disease. Technical progress towards methods of motion-free MRI and concepts of liver-specific contrast agents are presented. The potential impact of these developments on clinical medicine is discussed. PMID- 8193520 TI - Old wine into new bottles. A critical evaluation of transdermal clonidine in the treatment of hypertension. PMID- 8193521 TI - Hypertension and coronary heart disease risk factor management. AB - The primary goal in the treatment of essential hypertension is to reduce all end organ damage, not simply to reduce blood pressure. Hypertension is associated with an increased risk of cerebrovascular, cardiovascular and renal morbidity and mortality. Pharmacological therapy has reduced some, but not all, of these complications. In order to achieve maximal decrease in morbidity and mortality in hypertensive related diseases the overall impact of antihypertensive drug therapy on the pathogenesis of damage to each end organ must be considered. The pharmacological therapy of mild hypertension has reduced complications of most pressure related (arteriolar) damage such as cerebrovascular accidents, congestive heart failure, and some cases of chronic renal failure, but atherosclerotic complications, coronary heart disease, angina, myocardial infarction and sudden death have not been convincingly reduced. A more pathophysiologic and individualized approach to the treatment of hypertension is recommended in place of the traditional stepped care approach which has primarily emphasized diuretics and beta blockers as initial therapy. This new approach in the subsets of hypertension, which is based on eight parameters: (1) Pathophysiology; (2) Haemodynamics; (3) End organ damage; (4) Concomitant medical diseases and problems; (5) Demographics; (6) Adverse effects of drugs and quality of life; (7) Compliance with medication regimen; (8) Total health care costs: direct and indirect costs. Hypertension is not just a disorder of increased intraarterial pressure, but in fact, a syndrome of commonly associated genetic and/or acquired abnormalities including dyslipidaemia, insulin resistance, impaired glucose tolerance, central obesity, renal abnormalities, structural abnormalities of smooth muscle, and abnormal cellular cation transport or membranopathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193522 TI - Effect of antihypertensive formulation on health service expenditures. AB - A major barrier to the management of hypertension is the extent to which patients comply with the treatment regimen. Herein we report the findings of a retrospective analysis designed to discern the relationship between antihypertensive formulation, regimen compliance and the utilization of health care services. Data for this analysis were derived from the state of South Carolina's Medicaid computer archive. The study population consisted of 1,000 randomly selected beneficiaries initially prescribed one of the following antihypertensive regimens as monotherapy: atenolol (daily); captopril (twice daily); oral clonidine (twice daily); transdermal clonidine (once a week); diltiazem (twice daily); enalapril (twice daily); metoprolol (twice daily); prazosin (twice daily); terazosin (daily); and verapamil-SR (daily). Multivariate regression analysis was used to determine the incremental influence of selected demographic characteristics, utilization of medical services prior to diagnosis for hypertension, initial antihypertensive medication, medication possession ratio for antihypertensive therapy, and the number of maintenance medications for disease state processes other than hypertension on post-period health care expenditure. Results indicate that patients initially prescribed antihypertensive medication requiring daily or weekly administration experience infrequent changes in their therapeutic regimen, far less use of concomitant therapy for blood pressure control, an increased utilization of antihypertensive medication, and a decrease in the use and cost of physician, hospital and laboratory services. PMID- 8193523 TI - Dose linearity of clonidine after transdermal application. AB - A prerequisite for optimal antihypertensive treatment is the possibility of individualized dosing. Therefore, three different dosages of the clonidine containing transdermal systems have been developed. The aim of this analysis was to clarify whether a linear enlargement of system size and consequently, a linear increase of the dose coming into contact with the skin will result in a linear increase of bioavailable drug. Data sets were obtained from a study performed in healthy volunteers, who wore these different TTS systems for 7 days each. Every patch was analysed after removal for residual content of clonidine. Plasma levels were measured. The areas under these plasma level curves were calculated by the trapezoidal rule. Apart from the dose of clonidine in the patch, the actual released amount of drug from the patch as well as the area under the plasma level curve were the parameters selected for the data analyses. Plasma levels of clonidine are known to vary within individuals. However, we have shown that within the range 2.5-7.5 mg of clonidine, the area under the plasma level curve as well as the released amounts of drug increase linearly with the dose administered. The regression analysis of released amounts versus the area under the plasma level curve further supports linearity of dosage. PMID- 8193524 TI - Efficacy and safety of two different galenic formulations of a transdermal clonidine system in the treatment of hypertension. AB - The efficacy and safety of two different galenic formulations of transdermal clonidine systems were compared in 905 patients with mild to moderate essential hypertension during a 12 weeks observation period. 449 patients were treated with the matrix controlled clonidine transdermal (C-TD) system and 456 patients with the membrane controlled clonidine system (C-TTS). The mean blood pressure was reduced from 168/102 mmHg to 146/87 mmHg in the C-TD and from 169/102 mmHg to 148/88 mmHg in the C-TTS group. There was no difference in the response rate. The pattern of systemic side-effects appeared to correspond to those seen during oral clonidine treatment but with a lower frequency and intensity. The C-TD patch improved skin tolerability and the drop-out rate due to skin reactions was 2.2 times lower compared with the C-TTS group. Local skin reactions led to withdrawal in 35 of 449 C-TD treated and in 79 of 456 C-TTS treated patients. In conclusion, the improved carrier system for the transdermal clonidine treatment reduced local side-effects which in turn may further enhance acceptability and compliance in treated patients. PMID- 8193525 TI - One year efficacy and tolerability of clonidine administered by the transdermal route in patients with mild to moderate essential hypertension--a multicentre open label study. The Antihypertensive Patch Italian Study (APIS) Investigators. AB - The clonidine patch offers for the first time the unique possibility of a once-a week transdermal therapy of hypertension due to direct absorption of clonidine through the skin. The present study investigates the efficacy and safety of the transdermal administration on a sample of the Italian population. 101 patients entered the study, 51 male, 50 female (mean age: 53 years, SD +/- 10; range: 30 71 years), they were given clonidine by a therapeutical transdermal system as starting dosage. If blood pressure was not adequately controlled (DBP < 90 or 10 mmHg decreased from baseline value) the dosage was increased on a 2 week basis assessment. The patients were then followed for 12 months after the start of treatment. The decrease in both systolic and diastolic blood pressure continued up to one month after start of treatment and remained constant for at least 9 months. A total of 70% of the patients were controlled by the antihypertensive treatment as monotherapy, while in 6% additional combination with a diuretic lead to blood pressure control. 5% of the patients showed no reduction in blood pressure at the end of the titration phase. 24 (23%) patients complained of skin reaction; 21 patients of these (ten male, eleven female) were withdrawn from the trial due to predefined skin reaction criteria. No serious side effects have been observed during the run of the study. No rebound phenomena occurred in the week after treatment discontinuation. It is concluded that the transdermal treatment of hypertension with a clonidine containing transdermal system is therapeutically effective and probably associated with a high acceptability and increased compliance. PMID- 8193526 TI - Long-term (5 year) experience with transdermal clonidine in the treatment of mild to moderate hypertension. AB - The long-term safety and efficacy of transdermal clonidine (C-TTS) was evaluated in 102 patients with mild to moderate hypertension over a mean treatment period of 4.9 +/- 1.4 years. C-TTS size 1 was used by 29.4%, C-TTS size 2 by 35.3%; in 35.3% of the patients a diuretic agent was given in addition. The baseline blood pressure of 168/100 mmHg was reduced to 150/85 mmHg at the end of titration and remained stable during long-term treatment. After 5 years seated blood pressure was 147/83 mmHg. Systemic side-effects, e.g. 4.9% dry mouth, were reported mainly during the first month. Transient local side-effects occurred mainly between weeks 4-26, thereafter the incidence clearly diminished and did not cause any withdrawal due to skin reactions from 1 year up to 6.5 years. Overall the long term transdermal clonidine treatment was highly accepted by the patients, was effective and was well tolerated. PMID- 8193528 TI - The sympathetic nervous system and hypertension: mechanisms and treatment. PMID- 8193527 TI - The USA experience with the clonidine transdermal therapeutic system. AB - Cardiovascular diseases are the leading causes of death in the United States, with hypertension being amongst the most prevalent of the cardiovascular risk factors. Improvement of hypertension management has, in consequence, received much attention. Extensive pre- and post-marketing experience with the transdermal formulation of clonidine marketed in the USA in the mid-1980s has now been accumulated. Transdermal clonidine is effective as monotherapy in mild-moderate hypertension, and in combination with diuretics, calcium antagonists and ACE inhibitors in more resistant cases. It controls blood pressure throughout the 24 h circadian cycle. It is effective and generally well-tolerated in adolescents, the elderly, blacks, diabetics, and subjects with chronic renal insufficiency. It has been used perioperatively and for suppression of adrenergic symptoms in subjects withdrawing from addicting substances. In comparison with oral clonidine, transdermal clonidine reduces the incidence and severity of such symptomatic side-effects as dry mouth, drowsiness, and sexual dysfunction. Minor skin reactions occur at the site of application of the transdermal patch with moderate frequency. Adherence to transdermal clonidine therapy is high, and patients commonly prefer it to oral therapy. Transdermal administration of clonidine is a useful therapeutic advance in the long-term management of hypertension. PMID- 8193529 TI - Signal transduction and growth control in normal and cancer cells. PMID- 8193530 TI - Myc-Max-Mad: a transcription factor network controlling cell cycle progression, differentiation and death. AB - The Myc oncoprotein dimerizes with its partner, Max, to bind DNA, activate transcription, and promote cell proliferation, as well as programmed cell death. Max also forms homodimers or heterodimers with its alternative partners, Mad and Mxi-1. These complexes behave as antagonists of Myc/Max through competition for common DNA targets, and perhaps permit cellular differentiation. PMID- 8193531 TI - Oncogenes and cell death. AB - Several recent studies have implicated oncogenes and tumour suppressor genes in the regulation of programmed cell death (apoptosis). Lesions in the cell death pathway appear to be important in both carcinogenesis and the evolution of drug resistance in tumours. They include deregulated expression of genes such as bcl 2, loss of p53, and autocrine activation of anti-apoptotic signal transduction pathways. Paradoxically, a number of dominant oncogenes appear to act as potent inducers of apoptosis. This suggests that the pathways of cell proliferation and cell death may be tightly coupled, an idea that may have dramatic implications for models of oncogene co-operation and carcinogenesis. PMID- 8193532 TI - Cell cycle targets of the DNA tumor viruses. PMID- 8193533 TI - Tumor suppressor genes. AB - The mutation of tumor suppressor genes is thought to contribute to tumor growth by inactivating proteins that normally act to limit cell proliferation. Several tumor suppressor proteins have been identified in recent years, but only two of them, p53 and pRb, are understood in detail. In the past year, a role has become apparent for both of these proteins in transcription and phosphorylation events required for passage of a cell from G1 to S phase. The pRb protein appears to prevent the function of transcription factors and other proteins needed for S phase until its inactivation by cyclin-dependent kinases in late G1. Induction of p53 by DNA damage may act to cause cell cycle arrest or cell death by altering the transcription program of damaged cells. A detailed molecular understanding of these growth regulators is now emerging, and is the subject of this review. PMID- 8193534 TI - Oncogenes and cell proliferation. PMID- 8193535 TI - Oncogenic activation of tyrosine kinases. AB - Tyrosine kinases comprise the largest group of oncoproteins, a fact that underscores the importance of reversible tyrosine phosphorylation in the regulation of essential cellular functions. Oncogenic activation of tyrosine kinases results in the constitutive activation of what is normally a conditionally regulated enzyme activity. Studies of tyrosine kinase oncoproteins, and a comparison with their corresponding proto-oncogene products, have identified important functional and regulatory domains within these proteins, positive and negative regulators of their enzyme activities and signalling cascades that control cell growth and differentiation. PMID- 8193536 TI - SH2/SH3 signaling proteins. AB - SH2 and SH3 domains are small protein modules that mediate protein-protein interactions in signal transduction pathways that are activated by protein tyrosine kinases. SH2 domains bind to short phosphotyrosine-containing sequences in growth factor receptors and other phosphoproteins. SH3 domains bind to target proteins through sequences containing proline and hydrophobic amino acids. SH2 and SH3 domain containing proteins, such as Grb2 and phospholipase C gamma, utilize these modules in order to link receptor and cytoplasmic protein tyrosine kinases to the Ras signaling pathway and to phosphatidylinositol hydrolysis, respectively. The three-dimensional structures of several SH2 and SH3 domains have been determined by NMR and X-ray crystallography, and the molecular basis of their specificity is beginning to be unveiled. PMID- 8193537 TI - Protein tyrosine phosphatases: characterization of extracellular and intracellular domains. AB - Protein tyrosine phosphatases (PTPs) play an important role in the regulation of cell growth and differentiation. With over 30 PTPs identified, the specific functions of these enzymes are now being addressed. The identification of extracellular domain receptor-like PTP interactions and the characterization of intracellular PTP 'targeting' domains represent recent efforts in this pursuit. PMID- 8193538 TI - Genetics of signal transduction: tales from the mouse. AB - Recent progress in understanding signal transduction owes much to new genetic approaches, first by unraveling the molecular basis of classic mutations, and then by the use of gene targeting. Recent studies have examined mammalian signal transduction from cell surface to nucleus, especially ligand-receptor systems and cytosolic signal transducers. PMID- 8193539 TI - The IRS-1 signaling system. AB - IRS-1 is a principal substrate of the insulin receptor tyrosine kinase. It undergoes multi-site tyrosine phosphorylation and mediates the insulin signal by associating with various signaling molecules containing Src homology 2 domains. Interleukin-4 also stimulates IRS-1 phosphorylation, and it is suspected that a few more growth factors or cytokines will be added to form a select group of receptors that utilize the IRS-1 signaling pathway. More IRS-1-like adapter molecules, such as 4PS (IRS-2), may remain to be found. PMID- 8193540 TI - Receptor tyrosine kinases and their targets. AB - One of the ways in which higher eukaryotes receive messages from the environment is via cell surface receptor tyrosine kinases. These are transmembrane proteins with an extracellular binding domain that specifies the growth factor with which it will interact, and an intracellular domain that encodes the tyrosine kinase. The mechanism by which receptor tyrosine kinases direct intracellular signal relay appears to involve receptor autophosphorylation that permits the stable binding of SH2 domain containing signal transduction enzymes. Some of the more recent advances are summarized in this review. PMID- 8193541 TI - The hetero-oligomeric antigen receptor complex and its coupling to cytoplasmic effectors. AB - T-cell and B-cell antigen receptors are representative of a family of multisubunit receptors that utilize Src-family kinases as proximal cytoplasmic effectors in signal transduction. Recent studies have shown that distinct receptor subunits mediate ligand and effector interactions and demonstrate that physical interaction with effectors, and their activation, is a function of a 26 amino acid motif found in multiple receptor subunits. Further, receptor ligation induces tyrosine phosphorylation of this motif, and this initiates SH2-mediated association and activation of Src-family kinases and, apparently, ZAP70 kinases. Finally, this association triggers SH3-mediated binding of Lyn and Fyn to PI3-K, resulting in PI3-K activation. An integrated model of signal transduction is presented. PMID- 8193542 TI - Genetics of signal transduction in invertebrates. AB - Receptor tyrosine kinases regulate a number of different cell fate decisions during invertebrate development. Genetic analysis of the signal transduction pathways activated by these kinases suggests that they converge upon a common pathway involving Ras and a cascade of cytoplasmic kinases, diverging again in the nucleus with the regulation of specific transcription factors. PMID- 8193543 TI - Activators and effectors of ras p21 proteins. AB - Over the past year, major advances have been made in understanding the key steps involved in signaling pathways--from receptor tyrosine kinases to ras p21, and on to a cascade of serine/threonine kinases. A chain of specific protein-protein interactions is responsible for signal transduction. Components of the pathway are highly conserved between flies, nematodes and mammals, and constitute a primary signaling device in most cell types. PMID- 8193544 TI - Regulation and function of the Rho subfamily of small GTPases. AB - During the past year, the small GTP-binding proteins Rho and Rac have each been shown to regulate a signal transduction pathway linking growth factor receptors to distinct changes in the actin cytoskeleton. A number of regulatory molecules for Rho-like proteins have been identified and some of these may cross-talk with the Ras signalling pathway. PMID- 8193545 TI - MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. AB - Signal transduction pathways that respond to external signals through the MAP kinase family of protein kinases are involved in diverse responses in eukaryotic cells. MAP kinases are one element in a series of kinases that serve to connect the plasma membrane with cytoplasmic and nuclear events. MAP kinases have the unusual feature that their activation requires threonine and tyrosine phosphorylation carried out by a dual specificity protein kinase. Recent advances have shown that in two MAP kinase pathways (the mating response pathway in the fission yeast Schizosaccharomyces pombe, and receptor tyrosine kinase signalling), the small GTP binding protein ras p21 links membrane events to kinase pathway activation. PMID- 8193546 TI - Sex, stress and integrity: the importance of MAP kinases in yeast. AB - To coordinate responses to environmental and cell autonomous signals, Saccharomyces cerevisiae utilizes distinct MAP kinase dependent signal transduction pathways. This offers the opportunity to compare the activation and attenuation mechanisms of MAP kinases in a single organism, and raises the issue of how the specificity of the individual signal pathways is maintained. Although many recent advances in our understanding of these pathways are due to biochemical reconstitution experiments, the most surprising results and insights have come from genetic analyses. PMID- 8193547 TI - Ternary complex factors: growth factor regulated transcriptional activators. AB - Members of a family of Ets domain proteins, the ternary complex factors (TCFs), are recruited to the c-fos serum response element by interaction with the serum response factor. Recent findings indicate that phosphorylation of TCFs occurs in response to activation of the MAP kinase pathway, and that regulation of TCF activity is an important mechanism by which the serum response element responds to growth factor signals. PMID- 8193548 TI - Binding of carbohydrates to solid supports: evaluation of a prototype system. AB - Mono- and disaccharides were covalently and irreversibly bound to aminopolystyrene beads in good yield by heating in dilute aqueous solution. The degree and stability of sugar binding were determined by chemical and radiochemical methods and the accessibility of the bound sugars was demonstrated by exoglycosidase hydrolysis and by an enzyme-linked lectin-binding assay using Concanavalin A. PMID- 8193549 TI - Synthesis of methyl alpha-isomalto-oligosaccharides specifically deoxygenated at position 2 of the terminal glycopyranosyl unit. PMID- 8193550 TI - Structural analysis of novel rhamnose-branched oligosaccharides from the glycophosphosphingolipids of Leptomonas samueli. AB - Mild alkaline hydrolysis of the glycophosphosphingolipids of the protozoan Leptomonas samueli liberated several phosphoinositol-containing oligosaccharides (PI-oligosaccharides), which were purified by high performance anion exchange chromatography. The oligosaccharides in the resulting four fractions were characterized by methylation analysis, fast atom bombardment mass spectrometry and two-dimensional nuclear magnetic resonance spectroscopy. The oligosaccharides contain the core structure Man alpha (1-4)GlcN alpha (1-6)-myo-inositol-1-OPO3, and are substituted with 2 mol of 2-aminoethylphosphonate per mol of oligosaccharide. The nonreducing ends of the oligosaccharides were terminated by rhamnose branched neutral and acidic xylose-containing penta-, hexa-, hepta- and octasaccharides, of which the three most abundant were shown to have the structures: [formula: see text] More tentative structures are also proposed for three minor oligosaccharides. PMID- 8193551 TI - Will the transgenic mouse serve as a Rosetta Stone to glycoconjugate function? AB - The overwhelming diversity of oligosaccharide structures on glycoproteins and glycolipids is both the most fascinating and the most frustrating aspect of glycobiology. Moreover, a single protein may be variably glycosylated and thereby represented by multiple glycoforms. As envisioned, many modifications may serve no useful function while others are likely to be essential [1]; hence, experimental approaches to understand the biological basis for such complexity can be difficult to formulate. In a recent comprehensive review on oligosaccharide function [2], Varki concludes that oligosaccharides carry out a large number of biological roles and that 'while all theories are correct, exceptions to each can be found'. Although a common theme to oligosaccharide function may never appear, crucial biological information can be observed to reside within various glycoforms. Examples include the glycoform-dependent mechanism of selectin function in mediating haemopoietic cell extravasation during inflammatory responses [3] and the clearance of particular glycoforms from serum by various glycoform-specific receptors [4-6]. Together, studies of glycosyltransferase biochemistry, naturally-occurring and experimentally-induced glycoform mutations, and the genetic basis for the production of glycoform complexity have allowed crucial steps in the biosynthesis of specific glycan structures to be reconstructed as they appear to occur in the endoplasmic reticulum and Golgi apparatus of intact cells [7]. With a significant foundation of biochemical knowledge achieved, genetic approaches are under way further to decipher the physiological roles encoded within the diverse and dynamic mammalian oligosaccharide repertoire. PMID- 8193552 TI - Structure determination of the disialylated poly-(N-acetyllactosamine)-containing O-linked carbohydrate chains of equine chorionic gonadotropin. AB - The disialylated poly-(N-acetyllactosamine)-containing O-linked oligosaccharide alditols, released by alkaline borohydride treatment of the enzymically N deglycosylated beta-subunit of equine chorionic gonadotropin, were purified by fast protein liquid chromatography (FPLC) on Mono Q and analysed by fast ion bombardment mass spectrometry (FAB-MS) and 1H-NMR spectroscopy. The identified oligosaccharide alditols have the following structure: [Formula: see text] PMID- 8193553 TI - Biochemical characterization of the O-glycans on recombinant glycophorin A expressed in Chinese hamster ovary cells. AB - Alterations in N- and O-linked glycosylation affect cell surface expression and antigenicity of recombinant glycophorin A expressed in transfected Chinese hamster ovary (CHO) cells. To understand these effects further, glycophorin A was purified by immunoaffinity chromatography from transfected wild type and glycosylation deficient CHO cells. The O-glycans were characterized both biochemically, using gel filtration and high performance anion exchange chromatography, and immunologically, using carbohydrate specific monoclonal antibodies to probe Western blots. The O-glycans of human erythrocyte glycophorin A consist mainly of short oligosaccharides with one, two, or three sialic acid residues linked to a common disaccharide core, Gal beta 1-3GalNAc alpha 1 Ser/Thr, with the disialylated structure being the most abundant. With the exception of the trisialylated derivative, the same structures were found on recombinant glycophorin A expressed by wild type CHO cells. However, in contrast to human erythrocyte glycophorin A, the monosialylated oligosaccharide was the most abundant structure on the recombinant protein. Furthermore, recombinant glycophorin A was shown to express a small amount of the Tn antigen (GalNAc alpha 1-Ser/Thr). Recombinant glycophorin A had the same O-glycan composition, whether purified from clones expressing high or moderate levels of the recombinant glycoprotein. This indicates that the level of expression of the transfected glycoprotein did not affect its O-glycan composition. Deletion of the N-linked glycosylation site at Asn26, by introducing the Mi.I mutation (Thr28-->Met) by site-directed mutagenesis, did not markedly affect the O-glycan composition of the resulting recombinant glycoprotein expressed in wild type CHO cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193555 TI - TQM/CQI: is the game over or has it just begun? PMID- 8193554 TI - A lectin from the Asian horseshoe crab Tachypleus tridentatus: purification, specificity and interaction with tumour cells. AB - A lectin from the haemolymph of the Asian horseshoe crab Tachypleus tridentatus was purified to homogeneity by affinity chromatography on Sepharose 4B-bound N acetylneuraminic acid. The specificity of this lectin was studied by haemagglutination inhibition with sialic acid analogues, N-acetylhexosamines and glycoproteins. For the interaction with the agglutinin the N-acetyl group and the glyceryl side chain of N-acetylneuraminic acid are important, while presence of an aglycon, specially an alpha-glycosidically linked lactose increases affinity to the lectin. The strongest glycoprotein inhibitors were ovine as well as bovine submaxillary mucin and Collocalia mucin, all being O-chain glycoproteins but carrying completely different carbohydrate chains. The majority of N-chain proteins were inactive. As the lectin agglutinates human erythrocytes, but not the murine lymphoma lines Eb and ESb or the human colon carcinoma HT 29, these cancer cells apparently lack the 'Tachypleus tridentatus agglutinin-receptor' which is present on red cells and O-chain glycoproteins. PMID- 8193556 TI - Inappropriate clinical care in nursing homes. AB - Using secondary data, an analysis was done of the prevalence of inappropriate clinical care among 3,149 Virginia Medicaid nursing home residents. Six types of inappropriate care were examined: the underprovision of skilled nursing care, physical rehabilitation and routine medical care; and the overuse of psychotropic drugs, physical restraints and urinary catheterization. Thirty-two (32) percent of the residents received inappropriate care in at least one care area and 7% received inappropriate care in two or more areas. Residents who received the most inappropriate care were more dependent in their activities of daily living, uncommunicative, incontinent, likely to have had a stroke, and less disruptive. Residents who received the most inappropriate care are among the most vulnerable residents, and stronger regulation and outside advocacy may be needed to protect them from inappropriate care. PMID- 8193558 TI - The impact of managed care on the diagnosis and treatment of low back pain: a preliminary report. AB - Knowing when to use diagnostic testing and surgery in the management of low back pain is often a dilemma for practitioners. This paper reviews the effectiveness of clinical practice guidelines in managing 1,796 cases of low back pain or herniated lumbar disk reviewed by Health Risk Management, Inc. between November 1990 and October 1991. In all cases (except cauda equina syndrome or other rapidly progressing neurological deficit) a trial of conservative treatment, always including physical therapy, was requested prior to recommendation for diagnostic testing or surgery. Ninety-one percent (1,628 cases) had completed an adequate trial of conservative therapy or had a lesion requiring immediate intervention. These cases were recommended for the requested procedure or hospitalization. Of the 168 cases that were not recommended immediately for imaging, surgery, or hospitalization, 84.5% improved with conservative management and neither imaging nor surgery was necessary over a period of at least 12 months following the time of review. Efficacy of conservative management was independent of age, sex, part of the country in which the treatment took place, and primary diagnosis. Net savings realized after subtracting employer costs for the reviews were well over a third of a million dollars in this small group of patients. PMID- 8193557 TI - Enhancing faculty participation and interest in quality improvement in academic centers. AB - Continuous quality improvement (CQI) is necessary in maintaining and improving the quality of medical care delivered. However, quality assurance (QA) in the past was performed superficially to meet requirements of the Joint Commission on Accreditation of Health Care Organizations and other regulatory agencies. Academic faculty participation in QA activity was also limited. Faculty often assume that meaningful quality process demands excessive efforts and time unrewarded with career advancement, promotion, or monetary compensation. In addition, unstructured QA leads to duplication of data and loss of educational opportunity. We reorganized the QA process in internal medicine using the CQI concept to: (a) improve academic faculty participation, (b) incorporate educational concepts, (c) stimulate interest in outcome research and CQI, and (d) integrate cost containment. A reorganized CQI format has stimulated enthusiastic participation of faculty and residents, and has generated conferences and grand rounds pertinent to medical care, outcome research, and cost containment. We conclude that academic faculty should play leadership roles in the CQI process and include teaching models. Improved and increased academic faculty participation could be realized, when educational values, research activities, and cost analysis are incorporated into the CQI process. PMID- 8193559 TI - Economic credentialing: a poor title for a legitimate assessment concept. PMID- 8193560 TI - Innovations in case flow analysis: using midlier variance analysis. AB - This article presents the use of midlier and case flow analysis during a retrospective chart review to study the costs of hospital length of stay. The results showed that considerable savings can be realized by using these methods for one group of patients with the same diagnosis. We were able to redefine and track patients during their pre-, peri-, and postoperative period and estimated the time and cost opportunities for work flow improvement. We concluded that considerable savings are possible by extending the analysis to patients in other DRG groups. PMID- 8193561 TI - An outcomes analysis approach to utilization management: quality assessment of appropriateness of specialty referrals. AB - This report illustrates some methods by which to identify, guide, and develop acceptable levels of expected outcomes, defined as the validity or appropriateness of specialty referrals or procedures, through utilization management case studies and interventions. Outcomes variables may be used as standardized ongoing measures of cost-effectiveness and quality of health care services, focusing on appropriateness of utilization of specialty resources and health care technology. Community, regional, and national standards for such measures are currently being developed and evaluated for assessing the appropriateness of the use of health care technology. These standards for desired or expected outcomes need to become an integral part of utilization management as well as quality assessment and improvement, and are very helpful tools for developing specific interventions to be used for improving upon and documenting the cost-effective delivery of care within health services organizations. PMID- 8193562 TI - Corporate culture in a mythless society. PMID- 8193563 TI - Fractal dimension analysis of aluminum oxide particle for sandblasting dental use. AB - Aluminum oxide particles are commonly used as a sandblasting media, particularly in dentistry, for multiple purposes including divesting the casting investment materials and increasing effective surface area for enhancing the mechanical retention strengths of succeedingly applied fired porcelain or luting cements. Usually fine aluminum oxide particles are recycled within the sandblasting machine. Ceramics such as aluminum oxides are brittle, therefore, some portions of recycling aluminum oxide particles might be brittle fractured. If fractured sandblasting particles are involved in the recycling media, it might result in irregularity metallic materials surface as well as the recycling sandblasting media itself be contaminated. Hence, it is necessary from both clinical and practical reasons to monitor the particle conditions in terms of size/shape and effectiveness of sandblasting, so that sandblasting dental prostheses can be fabricated in optimum and acceptable conditions. In the present study, the effect of recycling aluminum oxide particles on the surface texture of metallic materials was evaluated by Fractal Dimension Analysis (FDA). Every week the alumina powder was sampled and analyzed for weight fraction and contaminants. Surface texture of sandblasted standard samples was also characterized by FDA. Results indicate very little change in particle size, while the fractal dimension increased. Fractal dimension analysis showed that the aluminum oxide particle as a sandblasting media should be replaced after 30 or 40 min of total accumulated operation time. PMID- 8193564 TI - Adhesion properties of plasma sprayed hydroxylapatite coatings for orthopaedic prostheses. AB - Using Air Plasma Spraying (APS) and Vacuum Plasma Spraying (VPS) techniques, hydroxylapatite (HA) and mixtures of HA and titanium (Ti) were deposited on a Ti6A14V alloy (and on an AISI 316L steel) subjected to different surface treatments. The deposits were investigated for their crystallinity, thickness, and adhesion properties. Higher adhesion values were obtained with VPS rather than with APS. By utilising VPS, the deposition conditions were selected in order to achieve crystallinity values between 70 and 90%. The adhesion results depend on the crystallinity (increasing with its decrease), on the thickness (decreasing slightly with its increase) and especially on the surface finish of the metallic substrate. A porous Ti precoat was more effective than either chemical etching in HCl or sandblasting; sandblasting being the least effective. In particular, the double deposits consisting of a porous Ti precoat and a successive layer of HA proved to be most interesting for their higher adhesion properties and for their capability of providing primary stability due to the presence of the HA and secondary stability, in the case of its reabsorption, due to the porous metal. PMID- 8193565 TI - Preparation and characterization of porous apatite ceramics coated with beta tricalcium phosphate. AB - Hydroxyapatite (Ca10(PO4)6(OH)2; HA) is one of the most biocompatible materials with bones, and porous HA is promising bone substitute materials for clinical applications. While there are reports that beta-tricalcium phosphate (Ca3(PO4)2; TCP) has higher resorbability than HA when the material is implanted in a bone defect. In the present study, porous HA coated with beta-TCP was prepared by our unique method. The porous HA of about 60% porosity with interconnecting pore structure was soaked in diammonium hydrogen phosphate solution, and then the HA was sintered at 900 degrees C for 3 h. beta-TCP was revealed by X-ray diffractometry on the surface of porous HA. It was possible to control the content of surface-formed beta-TCP arbitrary by varying the concentration of the solution. The obtained HA coated with 33 wt% beta-TCP (33TCP) had about 60% open porosity with the pore size from 150 to 400 microns. The average compressive strength of this porous ceramics was 17.5 MPa. Surface coated HA with beta-TCP deprived of the brittleness in handling. The weight of HA implanted into muscles was increased obviously at 4 weeks because of formation of carbonate hydroxyapatite on the surface of HA. The weight of 33TCP was scarcely changed up to 12 weeks, but the weight tended to increase at 24 weeks. The carbonate hydroxyapatite was not formed on 33TCP at 4 weeks, but formed on it at 24 weeks. Therefore beta-TCP coated porous HA behaved like beta-TCP initially after implantation, and then behaved like HA. PMID- 8193566 TI - Pressure sintering of apatite-collagen composite. AB - Preparation of a composite consisting of apatite and collagen was attempted. Starting from an aqueous solution of collagen, phosphoric acid, and calcium hydroxide suspension, an apatite (90wt%)-collagen (10wt%) composite of 1.75 g/ml in apparent density, with 2 GPa in Young's modulus, and 6.5 MPa in compression strength was synthesized at 40 degrees C, 200 MPa, successfully. It was found that the presence of liquid water in the system was essential for the sintering of the composite under high pressures. Without liquid water, the specimen that was pressure treated and brought in atmospheric pressure, broke into small pieces due to residual strain. The prepared composite could be cut by a razor blade, and was stable against immersion in water. The mean size of the apatite crystals in the composite was 10 nm in width and 40 nm in length. PMID- 8193567 TI - A motor-driven ventricular assist device controlled with an optical encoder system. AB - An electric motor-driven ventricular assist device has been developed for long term use inside the body. The system is composed of a pusher-plate-type blood pump and an actuator consisting of an electrical motor and a ball screw. Cyclic change of the direction of motor rotation makes a back-and-forth axial movement of the ball screw shaft. The shaft, which is detached from the pump diaphragm, pushes the diaphragm via a pusher plate to eject blood during systole; blood is sucked by the diaphragm resilience during diastole. Using the output signals from a newly designed, incremental-type, miniature optical rotary encoder mounted inside the actuator, the input voltage of the motor is optimally controlled referring to the phase difference between the current position of the moving rotor and the electrical reference signal of the rotation generated by a microprocessor-based controller. In vitro performance tests indicated that the system fulfills required specifications. The maximum efficiency was 11%, which was about twice as high as that obtained with the previous open-loop prototype system. In the air, the surface temperature of the actuator elevated to 20 degrees C above the room temperature. An acute in vivo test showed its feasibility as a left ventricular assist device. Analysis of the energy loss in each component of the system indicated that redesign and precise assembly of the mechanical parts could increase the system efficiency. PMID- 8193568 TI - Predictors of clinical wear of restorative dental composite materials. AB - The mode-I plane-strain fracture toughness values of eight posterior restorative composite materials were determined using straight-sided chevron-notch short-rod specimens and a special loading module. These results, together with the values of the modulus of elasticity, modulus of resilience, and flexural strength of these materials (as given in a paper by a previous worker) were used in a detailed correlational exercise, with the values of the clinical wear of restorations made from these materials (as given in the aforementioned paper) being the dependent variable. It was found that clinical wear may best be predicted using values of all four aforementioned mechanical properties. PMID- 8193569 TI - HLA-B and -DR match reduces the allograft reaction after keratoplasty. AB - Since 1983, corneal grafts have been routinely obtained from multiorgan donors and allocated to the patient with the greatest HLA compatibility. At follow-ups in 248 primarily clear corneal grafts, grouping according to the HLA mismatch rate revealed that the incidence of allograft reactions did not differ significantly for HLA-A but certainly did for HLA-B (P < 0.01) and, in patients with a poor prognosis, for HLA-DR as well (P < 0.05). Grouping the patients according to the mismatch rate of the total of four HLA-B and -DR antigens disclosed the incidence of allograft reactions to be markedly increased by a mismatch of more than two antigens (P < 0.05). The relative risk of an allograft reaction is increased by factors of 5.1 in patients with a good prognosis and 5.5 in those with a poor prognosis. The adverse influence of a postoperative inflammation on the occurrence of an allograft reaction as seen in nonmatched donor material is no longer present in matched donor material if the prognosis is good and no longer significant if it is poor (P < 0.09). The inflammation promoted expression of HLA antigens is of less importance for graft survival if the difference in the HLA antigens is reduced by the match. PMID- 8193570 TI - Basic fibroblast growth factor modulates corneal wound healing after excimer laser keratomileusis in rabbits. AB - We have previously demonstrated beneficial effects of basic fibroblast growth factor (bFGF) on corneal epithelial healing in different in vivo models. In the present study, we investigated the influence on epithelial and stromal healing of topical bFGF after excimer laser keratomileusis in a rabbit model. The corneas of 24 New Zealand white rabbits were deepithelialized (7-mm diameter) and subsequently received identical deep stromal laser ablations (depth, 50 microns; 6 D; diameter, 5 mm). The animals were randomly assigned to one of four treatment groups: PBS (control); bFGF at 500 ng/application; dexamethasone 0.1%, and bFGF+dexamethasone (n = 12 eyes/group). All treatments were given four times daily; with bFGF being given until complete epithelial healing and dexamethasone and PBS, until 3 months postsurgery. Wound surface regression on time was determined by means of computer-assisted image analysis of fluorescein-stained corneas. Corneal opacity was scored using slit-lamp observation and graded following a previously established scoring system. As compared with the other three treatment groups, a highly significant acceleration in the rate of epithelial wound healing was found after bFGF application for 2-3 days only (P < 0.001). A combined therapy (bFGF+steroid) had no effect on the healing rate. As compared with control values, the peak scores for subepithelial haze were significantly lower in eyes that had received bFGF; the regression on time of the haze in the growth factor group paralleled that in eyes receiving continuous steroid treatment. These results demonstrate for the first time the efficiency of a growth factor in modulating the wound-healing response after excimer laser photoablation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193571 TI - Laser sclerostomy ab externo using the erbium: YAG laser. First results of a clinical study. AB - A new approach to fistulating glaucoma surgery, laser sclerostomy ab externo, was investigated in a clinical study. A pulsed (200 microseconds) erbium-YAG laser was used, as its wavelength (2940 nm) is very well absorbed by tissue water. The laser energy was transmitted via a fiber to an application probe with a cannula particularly designed to guide another fiber into the subconjunctival space. Nine patients with advanced open-angle or neovascular glaucoma were treated. In all cases a functioning fistula with a prominent filtering bleb and a reduction of the intraocular pressure (from up to 50 mmHg to 8-18 mmHg) could be achieved. The total energy was 60 mJ on average. No complication occurred intraoperatively. Postoperatively, all fistulas in patients with neovascular glaucoma (n = 6) were impatent after approx. 7 days due to iris adherence to the internal ostium and episcleral scarring. In cases of open-angle glaucoma (n = 3) a patent fistula persisted for several months. Variation of the exposure parameters, the use of antiproliferative drugs, and a less restrictive selection of patients could further improve the success rate. PMID- 8193572 TI - Temporal summation measurements with the Octopus 1-2-3 perimeter. AB - Until recently, measurements of temporal summation required the construction of specialized instrumentation or the custom modification of an existing perimeter, which meant that such testing was unstandardized and relatively expensive. This precluded extensive use of this type of visual response testing, especially in a clinical setting. In an effort to change this situation, a personal computer (PC) program has been devised that makes use of a new interface for remote operation of the Octopus 1-2-3 automated perimeter. The program can be used to measure temporal summation at 1-5 locations in the visual field (0 degrees-30 degrees eccentricity) for 1-10 stimulus durations (5.6-999 ms) in the presence or absence of background illumination (10 cd/m2). Two auxiliary programs for analyzing the resulting data have been developed as well. Preliminary measurement trials were performed on four normal and two glaucomatous eyes at three test locations for ten stimulus durations in both the presence and the absence of background illumination. Ten examinations were carried out for each eye to reduce the effects of short-term fluctuations. The resulting temporal summation curves and the associated critical durations were similar to those found in the literature. No effect of disease on the critical duration was found (n = 2). With this program package, the effects of disease on temporal summation can now be tested using a commercially available instrument. To determine its clinical usefulness, though, investigations with larger populations will have to be made. PMID- 8193573 TI - Retinal hemodynamics after pars plana vitrectomy with silicone oil tamponade. AB - Pars plana vitrectomy with silicone-oil tamponade is frequently performed in cases of complicated retinal detachment. Because of the lower specific gravity and the lower surface tension of silicone oil in comparison with the aqueous phase of the vitreous, an influence on the blood flow in the retinal vessels would be expected. However, not only the silicone oil but also the operative trauma and a buckling procedure may have an influence on the retinal blood flow. To examine this question we measured the arteriovenous passage time in the silicone-oil-filled eye and in the contralateral eye in 14 cases using a laser scan ophthalmoscope at 3-5 days after surgery. The arteriovenous passage time is a parameter for the retinal microicirculation. In all cases we found a prolonged arteriovenous passage time in the silicone-oil-filled eye in comparison with the contralateral eye (mean value +/- SD, 2.5 +/- 0.8 vs 1.25 +/- 0.25 s; P < 0.01). The prolongation of arteriovenous passage times observed in silicone-oil-filled eyes indicates that the microcirculation is worsened at least during the early postoperative period. PMID- 8193574 TI - Cotton-wool spots as the initial ocular manifestation in Wegener's granulomatosis. AB - Various ocular manifestations have been described in Wegener's granulomatosis. Orbital involvement is common and manifestations in the anterior segment of the eye such as keratitis, scleritis, and conjunctivitis may occur. Involvement of the posterior segment presenting with major vascular occlusions or anterior ischemic neuropathy is rare. This case report presents a patient with bilateral cotton-wool spots at the posterior pole associated with histologically proven Wegener's granulomatosis. This finding, as an initial ocular manifestation of the disease, is very uncommon and may be interpreted as focal retinal inflammatory vasculitis. This was supported by the rapid positive response to systemic combined immunosuppressive and steroidal treatment during a 30-month period of review. The presence of cotton-wool spots in association with systemic signs of the disease should be considered in establishing the diagnosis of Wegener's granulomatosis. PMID- 8193575 TI - Solitary retinal granuloma as a presenting sign of sarcoidosis. AB - A 31-year-old white patient was referred with a recent history of decreased visual acuity in his left eye. A raised, greyish-white lesion close to the optic nerve was the only ophthalmological finding. Upon systemic work-up a chest X-ray revealed enlarged pulmonary lymph nodes. A biopsy obtained during bronchoscopy led to the diagnosis of sarcoidosis. No other manifestation was noted. Following systemic steroid treatment the lesion regressed and visual acuity improved. Granulomatous inflammatory diseases have to be ruled out in cases of prominent greyish-white fundus lesions. PMID- 8193576 TI - Results and prognostic factors in pneumatic retinopexy. AB - We analyzed 133 consecutive cases of primary retinal detachment treated by pneumatic retinopexy (PR). The postoperative follow-up period was at least 6 months (mean, 16.7 months; maximum, 36 months). In all, 97 cases (72.9%) were successfully treated by a single PR. In 19 cases (14.3%) primary reattachment was not achieved. In another 17 cases (12.8%) redetachment occurred. Redetachment was never observed later than 6 months following PR. It was caused by missed or new retinal tears in 8 eyes (6.0%) and by proliferative vitreoretinopathy in 7 eyes (5.3%). A final reattachment rate of 98.5% was achieved. Preoperative factors suggesting primary failure or redetachment were (1) extensive retinal detachment (P < 0.01), (2) pseudo- or aphakia (P = 0.01), (3) the retinal status of the fellow eye (P < 0.05), and (4) poor visual acuity in cases of attached macula (P < 0.01). In cases with preoperatively detached macula, visual acuity (VA) recovered considerably better following PR than following conventional buckling procedures. As compared with cases of successful PR, recovery of VA in all eyes requiring reoperation was significantly reduced. It was, however, still equivalent to the VA of eyes treated by scleral buckling. Surgical success is influenced by preoperative factors such as pseudo- or aphakia, extensive retinal detachment, poor initial VA in cases of attached macula, or the state of the fellow eye. These factors have to be taken into consideration in decisions for or against PR. The anatomical and functional outcome proves the value of this technique in the treatment of primary rhegmatogenous retinal detachment. PMID- 8193577 TI - Reconstruction of the anterior and posterior segment of the eye after massive injury. AB - We treated 15 patients whose common characteristic was a severe windscreen injury (7 eyes) or an (mine) explosion trauma (8 eyes), nearly always affecting both eyes. In several operations we tried to reconstruct the anterior and posterior segments using a temporary keratoprosthesis for repair of the posterior-segment damage. In cases where the retina could be attached, the initial result was a functional stabilization and improvement. In 4 eyes we implanted an artificial iris diaphragm to prevent silicone-corneal contact. The long-term results will depend on the functionality of the ciliary body. PMID- 8193578 TI - Penetrating keratoplasty and anterior segment reconstruction for severe ocular trauma. AB - The principles for management of acute ocular trauma are also applicable to the subsequent reconstruction of the anterior segment. As with the primary repair of ocular trauma, meticulous anatomical restoration during reconstructive surgery minimizes secondary complications and enhances the visual prognosis. Anterior segment reconstruction may then involve procedures such as stripping of corneal pannus, removal of lens and vitreous remnants, iris and angle reconstruction, intraocular lens implantation, and penetrating keratoplasty. A total of 39 consecutive cases of severe ocular trauma, which had undergone penetrating keratoplasty and anterior segment reconstruction, were evaluated for visual outcome, graft survival, and secondary complications. Post-operatively, 49% of eyes achieved > 20/100 as compared with 10% before surgery, and 72% improved by at least two Snellen lines. In all, 31 (80%) initial keratoplasties remained clear, as did all 4 subsequently regrafted corneas, for an overall keratoplasty success rate of 90%. Elevated intraocular pressure occurred postoperatively in 18 eyes (46%), and among these, 10 of 13 eyes (77%) had preoperative glaucoma, whereas 8 of 26 (31%) did not (P < 0.015). Peripheral anterior synechiae could be anatomically corrected at surgery in 80% of cases (24 of 30 eyes). Thus, despite major trauma and a high prevalence of glaucoma, both the visual and the anatomical improvements were highly satisfactory and without severe complications. PMID- 8193579 TI - Clonal analysis of rat tibia growth plate chondrocytes in suspension culture- differential effects of growth hormone and insulin-like growth factor I. AB - The number of growth hormone (GH) receptors in cultured rat epiphyseal chondrocytes are increased with numbers of cell divisions in monolayer. We wanted to study if increased number of cell divisions in monolayer influence GH or insulin-like growth factor I (IGF-I) response in a subsequent suspension culture. Primary isolated chondrocytes from rat tibia growth plates were cultured in monolayer at different seeding densities (4000, 8000 and 24,000 cells/cm2). After a culture period of 7 days, cells were trypsinized, counted and subcultured at 50,000 cells per dish in suspension stabilized with 0.5% agarose. 14 days later the agarose cultures were dried, stained and the number of clones with a diameter exceeding 50 microns was counted. Individual clones were classified as undifferentiated or differentiated according to the following criteria: cell clusters with a diameter of 50 microns and without matrix staining were classified as undifferentiated; cell clusters with a diameter over 50 microns consisting of 4 cells or more and with matrix stained by Alcian Blue were classified as differentiated clones. Human growth hormone (hGH) added to the suspension culture medium increased the number of undifferentiated clones if cells had been precultured at 4000 and 8000 cells/cm2 but hGH had no stimulatory effect on either clone type at 24,000 cells/cm2. IGF-I significantly increased the number of differentiated clones at all seeding densities while no effect was demonstrated on the number of undifferentiated clones. The results from the present study suggest that an increased number of cell divisions during primary monolayer culture increases GH responsiveness in a subsequent suspension culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193580 TI - Developmental regulation of growth hormone binding in the gilthead sea bream, Sparus aurata. AB - The occurrence of growth hormone (GH) binding was investigated in the gilthead sea bream larva, Sparus aurata, using recombinant trout GHII (rtGH) as a tracer. GH binding was detected in all the specimens examined (5, 17, 27 and 40 days after hatching). At 40 days after hatching, we observed a concentration of GH binding in the head region. Specific binding was dependent on protein membrane concentration and Scatchard plots showed a single class of high affinity and low capacity binding sites. Specific binding was inhibited by rtGH and ovine GH in a dose dependent manner. Chinook salmon prolactin and chinook salmon gonadotropin did not compete for 125I-rtGH binding sites. To our knowledge, this is the first report that indicates the presence of specific and saturable GH binding sites during early growth and development of a fish species. PMID- 8193581 TI - Involvement of G proteins in the effect of insulin-like growth factor I on gonadotropin-induced rat granulosa cell differentiation. AB - Insulin-like growth factor I (IGF-I) promotes gonadotropin-induced granulosa cell differentiation and proliferation. In order to investigate whether guanine nucleotide binding proteins (G proteins) may be linked, directly or indirectly, to some of the actions of IGF, the effects of cholera toxin (CT) and pertussis toxin (PT) on the enhancement by IGF-I of PMSG (pregnant mare serum gonadotropin) induced rat granulosa cell differentiation have been studied. This was done by the determination of progesterone production, aromatase activity and cAMP accumulation after a 48 h incubation with PMSG, IGF-I and PMSG plus IGF-I in cells treated with either CT or PT. Both CT and PT treatment stimulated PMSG induced progesterone production in granulosa cells after 48 h of culture with PMSG. CT treatment also stimulated aromatase activity in cells treated with PMSG and increased cAMP secretion under basal conditions (untreated cells) and in PMSG treated cells. Both CT and PT increased the stimulation by IGF-I of PMSG-induced progesterone production after 48 h of culture with PMSG plus IGF-I. Furthermore, CT augmented the enhancement by IGF-I of PMSG-induced aromatase activity and cAMP accumulation. In the absence of PMSG, CT did not increase steroidogenesis either alone or in the presence of IGF-I within the time frame studied even though CT was able to stimulate cAMP accumulation in untreated and IGF-I treated cells. These results suggest that G proteins have a role in the signalling cascade involved in gonadotropin-induced granulosa cell differentiation measured as PMSG mediated steroidogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193582 TI - The influence of body mass index on growth hormone secretion in normal and short statured children. AB - Obesity is one of the factors which limits the value of growth hormone (GH) provocation tests in the diagnosis of GH deficiency. We have therefore examined (1) the relationship between urinary GH (uGH), a physiological parameter of GH secretion, and percent ideal body mass index (BMI%), an indirect estimate of body fat, in 528 schoolchildren; and (2) the extent to which peak arginine stimulated (0.5 g/kg i.v.) GH concentrations were influenced by BMI% in 176 short normal (SN) children and 48 girls with Turner syndrome (TS). The mean BMI% (SD) for each group was 102.9 (10.8) in schoolboys, 102.7 (13.4) in schoolgirls, 95.8 (13.9) in SN boys, 98.2 (21.4) in SN girls and 105.9 (18.0) in TS. BMI% correlated inversely with log uGH in school-children (boys r = -0.16, P = 0.01; girls r = 0.25, P < 0.001). However, if each sex was subdivided by pubertal status, the inverse relationship only persisted in pubertal (boys r = -0.18, P = 0.04; girls r = -0.39, P < 0.001) but not prepubertal children (boys r = -0.1, P = 0.3; girls r = -0.11, P = 0.3). BMI% was also inversely related to log peak stimulated GH concentration in SN girls (r = -0.49, P < 0.001) but not SN boys (r = -0.14, P = 0.2) or girls with TS (r = 0.19, P = 0.2). The inverse relationship between normal body fat and physiological GH secretion becomes significant during puberty; in girls it accounts for 15% of the variability in uGH excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193583 TI - A mathematical model for appraisal of the impact of GH binding protein on GH receptor binding. AB - Discrepancies between GH measurements and growth rate of children have complicated diagnosis in a variety of clinical conditions. The competition of GH BP with the GH-receptor towards GH-receptor binding can have a role in these discrepancies. A mathematical model was developed for appraising the availability of GH for receptor binding from measurements of serum GH by RIA and serum GH binding protein (BP) by a binding assay. Eighteen patients with high GH-BP (obesity), normal GH-BP (normal control) or low GH-BP (children, anorexia nervosa or cirrhosis of the liver) were the subjects of this study. Sera of patients with high, normal or low GH-BP levels were analyzed for their competition with [125I]hGH binding to rabbit liver membranes. Serum GH was measured by a commercial polyclonal RIA. Serum GH-BP was measured by a binding assay with dextran-coated charcoal separation. Receptor availability for GH was assessed by displacing of [125I]hGH from rabbit liver membranes. The decline in receptor availability for each hGH value, caused by GH-BP competition with the receptor, was calculated by subtraction of the percent displacement in the absence of GH-BP from the percent displacement in the presence of a given GH-BP value. The results were analyzed statistically to give a series of polynomes. These enabled the calculation of an activity factor for serum RIA GH levels, that should predict the receptor availability of each GH level, according to the concomitant GH-BP level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193584 TI - Modification of catalytic properties of chicken liver fructose 1,6-bisphosphatase by allicin. AB - The activity of chicken liver fructose 1,6-bisphosphatase increases dramatically after incubation with allicin, a major biologically active compound produced by garlic. Activation is more pronounced when the enzyme is assayed with Mn2+ than Mg2+. Maximum activation is accompanied by the disappearance of 4 highly reactive sulfhydryl groups per molecule of enzyme. This modification also leads to loss of activation by K+, and reduced sensitivity to inhibition by AMP, fructose 2,6 bisphosphate, and high concentration of fructose 1,6-bisphosphate. All the altered properties induced by allicin can be reversed by dithiothreitol or tris(2 carboxyethyl)phosphine, the latter being much more effective. PMID- 8193585 TI - All 4 bases of both strands at -9 and -8 in T7 promoter are needed to be substituted by SP6-specific bases to switch promoter specificity. AB - It has previously been shown that a substitution of two base pairs at -9 and -8 in T7 promoter by SP6 promoter-specific base pairs alone is sufficient to make the T7 variant become an SP6 promoter, abolishing T7 promoter activity [Lee, S. S., and Kang, C. (1992) Biochem. Int. 26, 1-5]. In order to determine which of the 4 bases on both strands at the two positions is involved in the discriminative specificity, each base or each pair of bases was substituted by SP6-specific base(s), allowing one or two mismatches. The results show that all four-base substitution only is capable of switching promoter specificity, and that all the four bases are substantially involved in T7 promoter activity. PMID- 8193586 TI - Study on the partial purification of gonadotropins and thyrotropin from deer (Cervus elaphus) pituitaries. AB - Deer pituitaries were extracted with Tris-Cl buffer and the extract was fractionated on Concanavalin A-Sepharose into an unadsorbed ConA I fraction and an adsorbed ConA II fraction. The ConA II fraction was chromatographed on CM cellulose to yield an unadsorbed CM I fraction and an adsorbed CM II fraction. The CM I and CM II fractions were then respectively subjected to ion exchange chromatography on DEAE-cellulose to give the resultant unadsorbed DEAE I and adsorbed DEAE II fractions. The ConA II CM II DEAE I fraction was the chromatographic fraction with the highest potency in stimulating testosterone production by isolated rat Leydig cells and the highest immunoreactivity in a rat luteinizing hormone (LH) radioimmunoassay (RIA). The ConA II CM II DEAE II fraction represented the fraction enriched in thyroid stimulating hormone (TSH). It exhibited cross reactivity in a rat TSH RIA and much lower LH bioactivity than the LH-enriched ConA II CM II DEAE I fraction. The ConA II CM I DEAE II fraction represented the follicle stimulating hormone (FSH)-enriched fraction. The ConA I fraction demonstrated negligible FSH immunoreactivity and LH bioactivity, indicating that most of deer FSH and LH were adsorbed on ConA-Sepharose. PMID- 8193587 TI - Sequence characterization of cardiotoxins from Taiwan cobra: isolation of a new isoform. AB - Cardiotoxins (or called cytotoxins) are a group of very basic polypeptides present in some snake venoms, which are especially abundant in Formosan cobras. Several cardiotoxins with distinct pharmacological and biochemical properties were isolated and purified from the Taiwan cobra venom (Naja naja atra) by employing sequentially preparative-scale cation-exchange chromatography on TSK CM 650 coupled with the improved separation of toxin components on reversed-phase HPLC based on their hydrophobicity. The complete sequences of six cardiotoxin analogues, including one novel isoform never reported previously in this venom, were determined by N-terminal Edman degradation with the automatic pulsed-liquid phase sequencer and comparison of amino-acid compositions of purified toxin components. This novel cardiotoxin, a basic polypeptide of pI 10.13, comprises about 5% of total crude venom. It consists of 60 amino-acid residues with four disulfide bonds and shares about 80-92% sequence identity with several cytotoxins isolated from varied sources of different snakes. A systematic structure comparison of six major cardiotoxin isoforms was made by the secondary-structure predictions and hydropathy profiles based on their primary sequences. It is of interest to find that some subtle differences among these natural cardiotoxin analogues may lie in the intrinsic differences of the surface hydrophobicity of these isotoxins. PMID- 8193588 TI - Characterization of three fibrinogenolytic proteases isolated from the venom of Taiwan habu (Trimeresurus mucrosquamatus). AB - Snake venoms, particularly those belonging to Crotalidae and Viperidae families, are known to possess fibrinogenolytic proteases which strongly affect the blood coagulation system. Three fibrinogenolytic enzymes, named as TM-1, TM-2 and TM-3, were purified from the venom of Taiwan habu using anion-exchange and gel filtration chromatographies followed by cation-exchange HPLC. These enzyme fractions were shown to be homogeneous as judged by SDS-gel electrophoresis. Further characterization of these purified fractions with fibrinogenase activity indicated that they are single-chain proteases possessing basic isoelectric points and molecular masses of approximately 27 kDa. These enzymes cleaved alpha chain of fibrinogen first and then beta-chain, with relatively low activity on gamma-chain. Fibrinogenolytic activities of these enzymes were not significantly affected at extreme pH values, activity loss occurred only at temperatures higher than 65 degrees C. Enzyme activities were strongly inhibited by some metal chelators such as EDTA or 1,10-phenanthroline, suggesting that these fibrinogenases belong to metalloproteases. The closely similar amino-acid compositions coupled with identical cleaved products of similar molecular masses observed on the autolysis of TM-1 and TM-2 suggest that these two proteases are similar in primary structures and probably mutually related. PMID- 8193589 TI - Comparison of the cytotoxic activity of the immunotoxins with different internalization rate. AB - In comparative experiments the conjugates of A-chain of a plant toxin ricin (RTA) and monoclonal antibody (MAb) HAE9 (IgM) directed against human erythroblast antigen (Ag-Eb) or Mab HAE3 against human glycophorin-A and immunotoxins (IT) directed to CD5 and CD7 antigens of human T-lymphocytes have been investigated. Proceeding from the number of receptors on a cell, we compared efficiency of the cytotoxic effects of the conjugates with different internalization rate. The efficiency of immunoconjugates against Ags with an extremely high internalization rate was only slightly higher than that of immunoconjugates against Ags with a lower internalization rate. The enhancing effect of ammonium chloride on immunoconjugate cytotoxicity was more pronounced in the case of immunotoxins with a high internalization rate. PMID- 8193590 TI - Structural classification of the P450 superfamily based on consensus sequence comparison. AB - The novel method for classification of P450s has been proposed basing on consecutive multiple alignments of consensus sequences. A code can be assigned to each P450 amino acid sequence reflecting its relative distance from the corresponding consensus sequences at three hierarchical levels. Thus, only the principle of sequence similarity is chosen for classification without involving such criteria as enzymatic properties, phylogenetic assignment or chronology. PMID- 8193591 TI - Trehalose metabolism during sporulation in Saccharomyces cerevisiae. AB - S. cerevisiae has at least two enzymes for trehalose synthesis. In this paper we report some characteristics of the ADPG-dependent trehalose-6-phosphate synthase. As opposed to the UDPG-dependent enzyme, the ADPG-dependent activity did not respond to a glucose signal nor to a heat shock. Mutant strains, deficient in the UDPG-dependent enzyme but possessing the ADPG-dependent activity, did not accumulate trehalose either during growth or during sporulation. A diploid, homozygous for the deficiency in the UDPG-dependent synthase activity, was constructed. During sporulation the ADPG-dependent activity remained constant. However, when mutant spores were subjected to a glucose signal, trehalose was accumulated to the same extent as in control spores. PMID- 8193592 TI - Identification of buccal mucosal mucin receptor. AB - A receptor for salivary mucin was isolated from epithelial cell membrane of buccal mucosa by a procedure involving membrane solubilization with octylglucoside followed by affinity chromatography on Sepharose-bound wheat germ agglutinin. The receptor protein displayed an apparent molecular weight of 97kDa and exhibited binding specific to mucin in a concentration-dependent manner. The receptor, furthermore, showed a requirement for carbohydrate chains in mucin for binding, as their removal caused a marked (89%) reduction in binding capacity. Scatchard analysis revealed a linear plot with a single class of high affinity binding (Kd = 1.1 microM; Bmax = 7.68nmol/mg protein. The results provide for the first time evidence for the existence in buccal mucosa of a specific receptor for salivary mucin. PMID- 8193593 TI - Trichosanthin, a ribosome inactivating and anti-HIV protein, does not alter the concentration of beta-endorphin in the mouse brain. AB - Trichosanthin was administered intramuscularly into mature male ICR mice at a dosage of 0.2mg/25g, daily for three days. The mice were sacrificed four hours after the last injection. Their brains were dissected out and divided into three regions: A(thalamus and hypothalamus), B(cerebral cortex) and C(cerebellum and brainstem). Their pituitaries were also removed. The pituitaries and the various brain regions were extracted with hot 1M acetic acid. The extracts were lyophilized and reconstituted in radioimmunoassay (RIA) buffer before assay for beta-endorphin by RIA. It was found that there was a significant elevation of beta-endorphin concentration after trichosanthin treatment only in brain region A. The data suggest that trichosanthin does not adversely affect the brain. PMID- 8193594 TI - Chemical modification of histidine residue in substrate-binding domain of carbonyl reductase from rabbit kidney. AB - Carbonyl reductase from rabbit kidney was rapidly inactivated by diethylpyrocarbonate (DEPC). A similar inactivation was observed in photooxidation of the enzyme by methylene blue. The inactivation by DEPC was time and concentration-dependent and followed pseudo-first-order kinetics. The results obtained from the inactivation kinetics and the protective effect of 4 acetylpyridine (4-AP) with NADP+ against the inactivation led to the idea that one essential amino acid is located in substrate-binding domain of the enzyme. The treatment of the enzyme with DEPC formed N-carbethoxyhistidine. Judging from the effect of 4-AP with NADP+ on the formation of N-carbethoxyhistidine, it is concluded that one histidine residue is located in substrate-binding domain of the enzyme. Furthermore, whether one essential amino acid inactivated by DEPC corresponds to one histidine residue modified with DEPC is discussed. PMID- 8193595 TI - 5-Fluorouracil modulates aminoacylation of rat liver tRNA. AB - Among the different classes of RNA, the effect of 5-fluorouracil (FUra), an anticancer drug, has been studied extensively on tRNA function in E. coli, but to a limited extent in eukaryotes, with specific reference to the mammalian system. Here we compared the aminoacylation function of rat liver tRNA substituted with FUra. Three hours after a single i.p. injection of 50, 250 or 500 mg/kg body wt. of FUra, total tRNAFUra50, tRNAFUra250, and tRNAFUra500, respectively were isolated from the livers of 2-3 month old male Wistar rats. The activity of tRNAFUra was compared with normal tRNA (tRNAN) isolated from saline-treated controls. tRNAFUra50 accepted [14C]-labeled total and five individual amino acids (lysine, aspartic acid, methionine, tryptophan, and serine) at a significantly higher rate compared to tRNAN. On contrary, tRNAFUra250 & 500 displayed a dose dependent inhibition in aminoacylation with total amino acids, lysine, and methionine. Acceptance of leucine was inhibited by tRNAFUra in a dose-dependent way. Overall, the amino acid acceptance was variable among the three populations of rat liver tRNAFUra isolated with varying doses of FUra and the possible reasons for the altered function of tRNA are discussed. PMID- 8193596 TI - Glucose, glycated hemoglobin and fructosamine levels in essential hypertension. AB - It has been shown that a significant correlation is present between blood pressure and plasma glucose concentrations among nondiabetic individuals. Blood glycated hemoglobin, serum glucose and fructosamine concentrations were determined in forty nonobese individuals, twenty with untreated essential hypertension and twenty with normal blood pressure. The results demonstrated a decrease in fasting serum glucose and blood glycated hemoglobin values in hypertensive group compared to the healthy controls. Although, a minor decrease is observed in hypertensive group, no significant alteration is detected in fructosamine values between these two groups. PMID- 8193597 TI - Effect of thyroxine on DNA methyltransferase activity in cerebellum of rat. AB - DNA methyltransferase activity increased significantly in cerebellum from day 4 to day 8 and decreased in 30 day old rats. It was maintained at lower levels in the adult rats. Thyroxine administration markedly stimulated DNA methyl- transferase activity in the newly born pups. However, it did not cause any effect on this enzyme activity in 8 day old rat cerebellum. These results show that thyroxine has a role in the regulation of DNA methyltransferase activity in cerebellum of rat during early stages of development. PMID- 8193598 TI - Methyl xanthine and altered biomembrane dynamics: demonstration of protein mobility and enzyme inhibition by caffeine in sperm model system. AB - Treatment of spermatozoa with 10 mM caffeine increases the rotational mobility of thiol-containing proteins in a defined micellar micro-environment. This is associated with inhibition of superoxide dismutase activity and augmented superoxide anion radical generation. Increased sperm competence in presence of caffeine in human oligospermia is explained by these observations. Inhibition of cyclic phosphodiesterase by caffeine is suggested to be part of the observed lattice-rearrangement. PMID- 8193599 TI - Biological and immunological activities of bovine placental gonadotropin. AB - A bovine placental extract was fractionated on a Concanavalin A (ConA)-Sepharose column into an unadsorbed ConA I fraction and an adsorbed ConA II fraction. The ConA II fraction was then separated by gel filtration on Sephadex G-100 into void volume material (ConA II Sephadex fraction I) and retarded material (ConA II Sephadex fraction II). Con A II Sephadex fraction II was considerably more potent than ConA II Sephadex fraction I in stimulating testosterone production by isolated rat Leydig cells. Con A I fraction was inactive in this regard. None of the aforementioned fractions manifested follicle stimulating hormone (FSH) bioactivity. ConA II Sephadex fraction II yielded a displacement curve parallel to the standard curve in radioimmunoassays for rat luteinizing hormone and thyroid stimulating hormone (TSH), but it did not cross-react in a radioimmunoassay for rat FSH. ConA II fraction did not exhibit FSH bioactivity. The results indicate that bovine placental gonadotropin possesses luteinizing hormone-like bioactivity and immunoreactivity and TSH immunoreactivity but neither FSH bioactivity nor immunoreactivity. PMID- 8193600 TI - Deficiency of pyruvate dehydrogenase complex in tissues of an eight month old infant. AB - A metabolic investigation was carried out in an eight-month old infant with intrauterine hypotrophia, failure to thrive, psychomotoric retardation and cerebral atrophy, who died after respiratory infections. Blood analysis revealed intermittent lactic acidosis with normal lactate/pyruvate ratio. Activities of cytochrome c oxidase in skeletal muscle, heart, liver and fibroblasts were all in the reference range of controls. Activity of pyruvate dehydrogenase complex (PDH) was decreased in muscle homogenate, heart and liver mitochondria but was normal in cultured skin fibroblasts. Immunodetection of PDH subunits, and assay of El alpha phosphorylation showed in the patient decrease of E1 alpha in skeletal muscle, and enhanced level of E1 alpha phosphorylation in liver mitochondria. PMID- 8193601 TI - Cloning of a Streptococcus sobrinus oligo-isomaltosaccharide synthase gene and characterization of its product. AB - A Streptococcus sobrinus gene coding for a glucosyltransferase (GTF)-S was cloned into Escherichia coli, using the bacteriophage lambda L47.1 and the plasmid vector pACYC184. The MD124 clone obtained expressed a 155 kDa GTF-S which did not react with any antisera against GTF-S1, -S2 and -I enzymes. The recombinant enzyme (designated rGTF-S3) was homogeneously purified from the MD124 cell extract and characterized. The purified rGTF-S3 synthesized primer-independently alpha-1,6-linked linear oligosaccharides from sucrose. The dependence upon the sucrose concentration was diphasic, and the respective Km values were 1.3 and 25 mM. The properties except the Km values were similar to those of oligo isomaltosaccharide synthase from S. sobrinus AHT. PMID- 8193602 TI - Guanidine induced alterations in tissue transaminase patterns in the rat. AB - The effect of a uremic toxin, guanidine hydrochloride (GuHCl), on tissue transaminase patterns of rat was studied. Significant changes were reported in the transaminase activities of selected tissues. These changes may act to counter the effects of guanidine toxicity. PMID- 8193603 TI - Growth of rho 0 human Namalwa cells lacking oxidative phosphorylation can be sustained by redox compounds potassium ferricyanide or coenzyme Q10 putatively acting through the plasma membrane oxidase. AB - Pyruvate is conventionally used as a key growth supplement for mammalian rho 0 cells that lack mitochondrial DNA and are thereby devoid of oxidative phosphorylation. We have tested the proposition that cultured rho 0 human cells can be grown using redox compounds other than pyruvate. The results show that potassium ferricyanide and coenzyme Q10 can each be used to replace pyruvate to support the growth of rho 0 Namalwa cells (a lymphoblastoid cell line). Ferricyanide and coenzyme Q10 have both been reported as substrates for a plasma membrane NADH oxidase system which is capable of re-oxidising cytosolic NADH to NAD+. These compounds are also known to stimulate the activity of this enzyme system. We interpret our data to indicate that redox support for growth of rho 0 human cells can be achieved by external electron acceptors such as ferricyanide (a plasma membrane impermeant compound), or coenzyme Q10 (an integral component of the plasma membrane oxidase), through the enhanced conversion of cytosolic NADH to NAD+. This re-oxidation of NADH enables glycolysis to function efficiently as the sole source of cellular ATP, in the absence of mitochondrial oxidative phosphorylation in rho 0 cells. This has important implications for the development of new strategies for the amelioration of the bioenergy decline that occurs in mitochondrial disease and during the human ageing process. PMID- 8193605 TI - Estimates of future global tuberculosis morbidity and mortality. PMID- 8193604 TI - Haemophilus B conjugate vaccination failure. PMID- 8193606 TI - The effect of salt loading on the urinary excretion of dopamine and sodium transport inhibitor in the rat. AB - 1. The temporal relationship between the excretion of dopamine and sodium transport inhibitor (STI) during salt loading was examined in the rat. 2. Urine samples were collected before and during salt loading (given as 18 g/l NaCl solution to replace drinking water) for the measurement of sodium, creatinine, dopamine and STI in 6 female rats. Dopamine was measured by HPLC and STI was extracted and measured by its ability to inhibit purified Na+, K(+)-ATPase enzyme. 3. Urinary sodium and STI (expressed in relation to creatinine) on day 1 of salt loading were 4.6 and 4.2 times respectively of the control values. Urinary excretion of dopamine did not increase significantly until day 2 when it was 21% higher. 4. The excretion of STI paralleled that of sodium excretion whereas the excretion of dopamine lagged behind. 5. We conclude that salt loading increases STI and dopamine and that the increase in STI precedes that of dopamine. PMID- 8193607 TI - Mineralocorticoid induced hypertension and noradrenaline spillover in man. AB - This study examined haemodynamics and noradrenaline spillover in five normal men before and on day 7 of oral fludrocortisone treatment, 0.3 mg/day. Resting systolic (105 to 115 mm Hg, standard error of the difference +/- 2.0, p < 0.01) and diastolic (65 to 73 mm Hg, +/- 3.0, p < 0.05) blood pressure increased, as did cardiac output, from 5.0 to 5.7 L/min (+/- 0.1, p < 0.01). Calculated total peripheral resistance fell from 21.2 to 20.0 mm Hg/L/min (+/- 0.4, p < 0.05). Fludrocortisone produced a fall in plasma potassium, renin and aldosterone concentrations and haematocrit and a rise in body weight. Cold pressor responses were increased by fludrocortisone, from 7.5 to 20 mm Hg (+/- 3.0, p < 0.01), and forearm vascular resistance rose 12 arbitrary resistance units (R) before and 36 R units after treatment (+/- 5.0, p < 0.01). Total body spillover of noradrenaline was decreased from 9.48 to 7.36 ng/kg/min (+/- 0.86, p < 0.05). There were no changes in forearm noradrenaline spillover at rest or during cold pressor stimulation. It appears unlikely that the sympathetic nervous system plays a major role in the pathogenesis of mineralocorticoid hypertension in man. PMID- 8193608 TI - Carvedilol, a novel cardiovascular agent, inhibits development of vascular and ventricular hypertrophy in spontaneously hypertensive rats. AB - The effects of carvedilol, a novel cardiovascular agent, were evaluated in developing spontaneously hypertensive rats (SHR) for effects on hemodynamics, and the ability to effect the development of left ventricular, and vascular hypertrophy associated with chronic hypertension. Chronic oral administration of low dose carvedilol (20 mg/kg/day) was initiated when rats were 5 weeks of age, and experiments progressed until 14 weeks of age. Carvedilol-treated SHR had significantly reduced systolic blood pressures and heart rates throughout the duration of the experiment, and had significantly reduced ventricle/body weights by approximately 9.0%. Morphologic analysis of tertiary branches of the mesenteric artery revealed that carvedilol-treated SHR had significant reductions in medial cross-sectional area. Carvedilol produced concentration-dependent inhibition of basal [3H]thymidine incorporation in cultured SHR vascular smooth muscle cells, as well as by stimulation produced by PDGF (1 nM), EDGF (1 nM), thrombin (0.5 U/ml), or endothelin-1 (1 nM), indicating that carvedilol had direct anti-mitogenic activity. The present studies demonstrate that low dose carvedilol produced sustained reductions in blood pressure and heart rate in developing SHR that were accompanied by significant inhibition in the development of vascular and myocardial hypertrophy. The morphological changes induced by carvedilol may be mediated by a combination of hemodynamic effects, as well as by direct anti-mitogenic effects on vascular smooth muscle. PMID- 8193609 TI - Evaluation of cilazapril versus captopril in patients with mild to moderate essential hypertension. AB - OBJECTIVE: Cilazapril, a long-acting angiotensin converting enzyme (ACE) inhibitor, was evaluated against captopril for safety and efficacy in the treatment of mild to moderate essential hypertension. METHODS: One hundred thirty two patients were randomly assigned to receive cilazapril, 2.5 mg once daily; 62 patients were randomly assigned to receive captopril, 25 mg twice daily. If necessary, dosage was increased to 5.0 mg cilazapril, once daily or 50 mg captopril, twice daily. Adjunctive hydrochlorothiazide (12.5 mg once daily) was later added to this higher dosage, if required. RESULTS: After eight weeks of monotherapy, sitting diastolic blood pressure (SDBP) had decreased 7.5 mm Hg from baseline for cilazapril-treated patients, versus 5.6 mm Hg for captopril-treated patients. These decreases were 7.6 mm Hg and 6.8 mm Hg for cilazapril and captopril, respectively, at Week 12. At Week 8, 36.5% of patients receiving cilazapril had achieved a SDBP of 90 mm Hg or less, versus 26.0% of captopril treated patients. The overall responder rate at Week 8 was 47.1% for cilazapril and 34.0% for captopril. None of these differences between the two treatment groups were statistically significant. Both drugs alone or in combination with hydrochlorothiazide were well tolerated during the 12-week treatment period. CONCLUSION: The results of this study indicate that cilazapril, alone or with adjunctive hydrochlorothiazide, is effective and well tolerated as treatment for mild to moderate hypertension. PMID- 8193610 TI - Lack of renal dopamine production during acute volume expansion in Dahl salt sensitive rats. AB - Endogenous kidney dopamine (DA) is reported to contribute to the natriuretic response to acute volume expansion (VE). Several studies suggest that a defect in renal DA-ergic system may play a role in genetic hypertension in humans and rats. The present study was performed to determine the role of renal DA and tubular DA 1 receptors in the natriuretic response to VE in age-matched inbred Dahl salt sensitive (SS/Jr) and salt resistant (SR/Jr) rats of 9-11 weeks of age. In pentobarbital anesthetized rats, VE was carried out by intravenous infusion of isotonic sodium chloride (5% body weight) over a period of 60 min. This maneuver evoked marked increases in urine output and urinary sodium excretion in both SR/Jr and SS/Jr species. However, the natriuretic and diuretic response to VE was significantly reduced in SS/Jr as compared to SR/Jr rats. It was also observed that the urinary excretion of DA was significantly increased during VE only in SR/Jr, but not in SS/Jr rats. In separate group of animals, infusion of DA (1 microgram/kg/min) produced similar increases in urine output and urinary sodium excretion without causing any alterations in blood pressure or heart rate in either SS/Jr or SR/Jr rats. These results suggest that SS/Jr rats are not able to eliminate an acute increase in sodium load as efficiently as SR/Jr, which may be partly due to an impaired endogenous kidney DA production. PMID- 8193611 TI - Growth properties and receptor expression in vascular smooth muscle cells from hypertensive rats. AB - The objective of this study was to evaluate the growth properties and receptor expression in aorta-ring derived smooth muscle cells (SMCs) cultured from control (WKY) and spontaneously hypertensive rats (SHR). SHR-SMCs exhibited a 3-4 day lag period before migrating. In addition, SHR-SMCs had a significantly higher growth rate, shorter population doubling time and higher saturation density level characteristics that were retained at higher passage levels. beta-adrenergic and angiotensin (All) receptors were measured using iodocyanopindolol (ICYP) and [3H] All, respectively. All receptor expression was similar in both WKY and SHR-SMC cultures. WKY-SMCs exhibited little ICYP binding (Bmax 8.27 +/- 2.0 fmol/mg) while SHR-SMC binding capacity was 8 fold higher (Bmax 65 +/- 9.2 fmol/mg). In addition, the responsiveness of the beta-receptor, as assessed by adenylyl cyclase stimulation, was similar for WKY and SHR-SMCs. These data suggest that factors regulating SMC receptor expression in vitro are selective since All and adrenergic receptor densities exhibit different responses to hypertension. PMID- 8193612 TI - Chronic monitoring of cardiovascular function in the conscious guinea pig using radio-telemetry. AB - An implantable radio-telemetry device for chronic monitoring of arterial pressure and heart rate in the conscious guinea pig was validated against measurements using an exteriorized, indwelling catheter. There were no significant differences between simultaneous measurements in animals instrumented with both the telemetry system and the conventional catheter (implanted 24 hrs prior to comparisons) in response to a variety of vasoactive agents. The device was shown to be accurate up to 3 weeks after implantation (longest time point tested). Resting pressures and heart rates in the telemetered guinea pig were stable in 100% of the animals tested. In contrast, animals instrumented with only exteriorized catheters showed a significant decline in pressure by 8 days after surgery and a 39% attrition rate due to loss of catheter patency. Performance of the telemetric device was examined in both normal and sodium-deficient animals, since the latter is a useful normotensive model in which blood pressure is rendered highly renin dependent for evaluating the efficacy of potential antihypertensive agents that target the renin-angiotensin system. The telemetered guinea pig is an appropriate model for assessing responses to chronic exposure of cardiovascular agents. PMID- 8193613 TI - Bronchial reactivity in a general population of north Italy: relationships with occupational exposure. AB - Two thousand eight hundred and forty one subjects, aged 8-73 yrs, took part in the second cross-sectional survey in the Po River Delta area: among them, a subsample of currently employed people, aged 14-71 yrs, was chosen to establish the relationship between occupational exposure to dusts, chemicals or gases and respiratory symptoms, lung function and bronchial reactivity. Each subject filled out the Italian National Research Council (CNR) standardized questionnaire concerning respiratory symptoms, diseases and risk factors. A variable proportion of subjects performed acceptable forced and slow vital capacity manoeuvres, diffusing capacity of carbon monoxide and bronchial challenge test to methacholine. Occupational exposure appeared to be related to prevalence rate of respiratory symptoms (wheeze, dyspnoea, presence of at least one respiratory symptom) and bronchial asthma. Consistent effects on lung function were not evident. With respect to the bronchial challenge test, using the measurement of the provocative dose producing a 20% fall in forced expiratory volume in one second (PD20) a significantly higher percentage of hyperreactive subjects was found among ex-smoker exposed men; a borderline higher percentage of hyperreactive subjects was also found in non-smoker exposed women. The study findings support the suggestion that occupational exposure may play a role in the development of airway obstructive diseases. PMID- 8193614 TI - Ectopic Cushing's syndrome in a patient with squamous cell carcinoma of the lung due to CRF-like production. AB - We present a patient with a poorly differentiated squamous cell carcinoma of the left lower lobe, who developed Cushing's syndrome. Adrenocorticotrophic hormone (ACTH) and cortisol levels in the blood were extremely elevated, but immunostaining for ACTH and corticotrophin releasing factor (CRF) of the primary tumour and metastases was negative. The ectopic Cushing's syndrome was probably caused by CRF-like production. PMID- 8193615 TI - An unusual increase in haemodynamic values in a sleep apnoea syndrome patient with prolonged apnoea. AB - This case report shows the results of a right heart catheterisation in a patient with sleep apnoea syndrome (SAS). Arterial oxygen saturation (SaO2), heart rate, oronasal flow, and monitoring of electroencephalographic (EEG), sovrayoidal electromyographic (EMG) and thoracoabdominal movements were recorded simultaneously. A mixed apnoea of 180 s was registered, SaO2 fell to 54% and systolic pulmonary artery pressure (sPAP) increased to 130 mmHg. Slowly, haemodynamic values began to normalise with the reappearance of respiratory acts. We can hypothesize that this patient's nocturnal apnoeas may cause frequent and deep negative pleural pressure swings, with severe continuous action on pulmonary circulation. This case report has shown that a SAS patient is capable of developing an adaptative response to an unusual and remarkable systolic pulmonary artery pressure increase, which is mainly due to hypoxic vasoconstriction. PMID- 8193617 TI - Severe community-acquired pneumonia "a new clinical concept". PMID- 8193616 TI - Pleural effusion: a clinical review. AB - Pleural effusion is a problem commonly encountered by chest physicians, accounting for approximately 4% of all attendances to the chest clinic. In spite of extensive investigations, a significant proportion (approximately 20%) of effusions defy a diagnostic label. This article discusses the role of established, and some of the newer, techniques which are now available for investigating pleural disease in a clinical setting. The initial approach towards a diagnosis usually begins by distinguishing between transudates and exudates, based on protein and lactate dehydrogenase (LDH) concentrations in fluid (usually in relation to their concentration in serum). The exact role of amylase and LDH (and their isoenzymes) may provide additional information towards a differential diagnosis of various exudative pleural effusions. With newer cytochemical staining techniques on pleural fluid, the diagnostic yield of malignant pleural effusions may be increased by up to 80%. Ultrasound (US) and computed tomographic (CT) scan of the chest have further enhanced the diagnostic yield of undiagnosed pleural effusions, especially in relation to the US or CT guided needle biopsy. The re-emergence of thoracoscopy as the latest diagnostic and therapeutic (e.g. pleurodesis) tool for undiagnosed or recurrent pleural effusions, may help in narrowing the diagnostic dilemma faced by clinicians. PMID- 8193618 TI - The chronopharmacological application of theophylline therapy in asthma. AB - It has been known for centuries that asthmatic patients experience a worsening of symptoms at night and early in the morning, thus disturbing sleep and in some compromising daily performance. Nearly 95% of asthmatic patients experience nocturnal symptoms severe enough to awaken them, at least periodically. A more feared consequence of nocturnal asthma than disruption of sleep in death. Patients who suffer from nocturnal asthma require bronchodilator treatment that is effective overnight. The efficacy of therapy depends upon it formulation and the treatment strategy that is employed. An ideal bronchodilator medication should have optimal effect at a time when enhanced bronchoconstriction is known to occur. Certain sustained-release theophylline (SRT) have been formulated as effective chrono-therapies for nocturnal asthma. The use of certain SRTs have proved highly successful in controlling asthma at night after being administered once-daily in the evening. PMID- 8193619 TI - The T-cell antigen receptor: methods of study and relevance in the pathogenesis of pulmonary disorders. AB - Each antigen (Ag)-driven immune reaction begins with Ag recognition by T lymphocytes through a surface molecular structure and T-cell antigen receptor (TCR). TCR is a proteid heterodimer, composed of an alpha and a beta chain (alpha beta+ T-cells) or of a gamma and a delta chain (gamma delta+ T-cells); each TCR chain is composed of two subunits the constant (C) region and the variable (V) region, whose combination is responsible, at least in part, for Ag specificity of each T-cell. Immune reactions toward known (e.g. tuberculosis) or unknown (e.g. sarcoidosis). Ags play an important role in the pathogenesis of many pulmonary disorders. The study of TCR may be performed at DNA, RNA and protein levels, applying molecular biology techniques. Using this molecular approach, it has been demonstrated, for example, that subgroups of patients have increased proportions of lung and/or blood T-cells bearing TCR with certain V regions of the alpha beta+ T-cells or of the gamma delta+ T-cells, suggesting that these cells were reacting toward antigenic stimuli. Similar results were obtained in tuberculosis, where an increase in gamma delta+ T-cells have been observed in peripheral blood of some patients. In asthma and in lung cancer a characterisation of TCRs of T cells reacting to the involved allergens or to the tumour-associated Ags is still lacking, although animal studies show a selection of allergen-specific TCRs among the airway T-cells, and the ability of tumour-infiltrating gamma delta+ T-cells to kill cancer cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193620 TI - Critical review of microbiological data and methods in diagnosis of lower respiratory tract infections. AB - A review is presented of the microbiological data, and the methods for obtaining these data, which are relevant for the diagnosis of lower respiratory tract infection. The necessity for adequate information exchange between the microbiology laboratory and the clinic is stressed. Once the specimen (usually sputum) has reached the laboratory, it is screened macroscopically and microscopically for adequacy, and cultures are set up. Many patients with acute community-acquired pneumonia (CAP) have no sputum, and some produce purulent sputum containing no obvious infecting micro-organisms. Despite modern microbiological techniques, only 110 out of 250 acute CAP patients had positive bacteriological cultures and 41 more yielded only positive serological results, so that an aetiological diagnosis was reached in 60%. Invasive methods of specimen collection (bronchoscopy, BAL, protected brush, etc) have also been studied, together with quantitative bacterial counting, but the results have not yielded so much useful information that these procedures can be unreservedly recommended. Molecular biological methods (DNA probes, PCR, etc) are only now becoming available. The bacteriological findings in patients with acute CAP have been compared with those in acute exacerbations of chronic bronchitis (CB), and several differences have emerged in the order of frequency of occurence. H. influenzae is in first place with exacerbations of CB, but is second to S. pneumoniae in acute CAP. The latter occupies third position in CB, with Moraxella catarrhalis second. The role of Chlamydia pneumoniae in acute CAP is not yet clear, but the serological results suggest an association in 42 out of 147 patients tested (29%), 15 of whom also had positive bacteriological cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193621 TI - Current role of vaccination in preventing acute respiratory infections in children in developing countries. AB - Acute respiratory infections (ARI) cause more than four million childhood deaths each year in developing countries. In addition to standard case management, vaccines have a great potential for reducing these deaths. Immunization against measles and pertussis, already reaching more than 70% of infants in developing countries, contributes to the prevention of more than one million childhood deaths. New conjugate vaccines against Haemophilus influenzae type b, if shown to be effective against pneumonia in developing countries, could reduce acute lower respiratory infection (ALRI) deaths by 4%. A further 10% reduction could be obtained by the availability of an effective conjugate vaccine against Streptococcus pneumoniae. A safe vaccine against respiratory syncytial virus could also prevent 10% of ALRI deaths. The potential role of other bacterial and viral vaccines needs to be clarified. PMID- 8193622 TI - Lymphangioleiomyomatosis: clinical course. AB - Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease of smooth muscle proliferation that generally leads to death, due to respiratory failure, within 10 yrs. The disease almost exclusively affects women of child-bearing age and rarely in postmenopausal years. High resolution computed tomographic (CT) patterns are characteristic and almost pathognomonic for LAM. Attempts to treat this disease with hormonal therapy have shown that a number of hormonal manipulations may not be helpful, but that surgical or radiant oophorectomy alone is the most effective treatment, even if the disease is so rare as to preclude randomized trials. Castration, as a means of early therapy, has been associated with a stable respiratory picture in our patients. PMID- 8193623 TI - Clinical application of lung function testing in ventilated infants. AB - Lung function (compliance, resistance and functional residual capacity), respiratory timing and ventilator-patient interaction can now be assessed in ventilator-dependent neonates. Such measurements have usually been made as part of research studies. Disease severity has been evaluated and prognosis predicted, the efficacy of many therapies, particularly surfactant, has been assessed by determining their ability to improve lung function. Measurement of ventilator patient interaction has been particularly useful to refine conventional ventilation and in the development of newer forms of respiratory support such as patient triggered ventilation. The recent arrival of commercially available computerized lung function systems may tempt clinicians to introduce respiratory measurements into their practice. Before such an approach is adopted, however, it is vital the potential problems, limitations and likely benefits are carefully thought through. PMID- 8193624 TI - The place of education in the management of chronic lung disease. AB - Health education, although an interesting logical requirement for management of chronic lung disease, is a complete process. It consists of more than transmission of a message with the expectation of implementation. The core materials can easily be identified, but the patient's response cannot be anticipated. Education of the health care providers, in this context respiratory physicians, regarding the second stage, should help to improve outcome. PMID- 8193625 TI - Techniques and impact of education in adult asthmatics. AB - A major cause for the discrepancy between the increase of mortality and morbidity due to asthma and advances in clinical assessment and treatment of the disease is inefficient asthma management. Patient education is a powerful tool for helping patients to gain the motivation and skills to control their asthma. An effective teaching and treatment programme for asthmatics should include information about the disease, prevention and treatment of asthma attacks and bronchial infections, and training of self-management of airflow limitation by the patients. On the basis of the currently evaluated programmes for asthmatic adults, patient education diminishes the frequency of asthma attacks and decreases the disability of the patients. By a reduction of emergency treatments, hospitalizations, and days lost from work a decrease in the costs of the often life-long treatment of asthmatics can be expected. Therefore, patient education should be an integrated part of current asthma management. PMID- 8193626 TI - Developing a quality-of-life questionnaire for patients with respiratory illness. AB - In this short report, the construction of a disease-specific quality-of-life questionnaire for patients with asthma and chronic obstructive pulmonary disease (COPD) is described. Some psychometric aspects are also discussed. We listed 221 items relating to several domains of quality-of-life, and asked 204 patients to indicate, on a seven-point Likert-scale, how much of a problem each item had been during the last year. After item selection, a quality-of-life scale was constructed, consisting of 55 items divided into 7 subscales. The reliability estimates vary from 0.68 to 0.89, and can be considered as quite satisfactory. Results concerning construct validity are promising; there is a strong relationship between the Quality-of-life subscales and several indicators of illness severity. Further research is called for to validate the questionnaire. PMID- 8193627 TI - Why quality of life measures should be used in the treatment of patients with respiratory illness. AB - Treatment of airways disease is directed towards improving patients' health and well-being. Measurements of airways function do not reflect all the disease activity present in the airways that may affect the patient. Spirometry correlates poorly with health. Physicians appear to estimate their patients' health using criteria different from the patients themselves. Quality of life questionnaires provide a method of quantifying the effect of disease on patients' lives. They can summarize a number of aspects of the disease and provide an overall estimate of the effect of disease and benefits due to therapy. They have the potential to identify a threshold response to treatment that may be considered "worthwhile", and allow comparison between therapies with respect to the health gain that each provides. PMID- 8193628 TI - Passive respiratory mechanics to assess lung function in infants. AB - In the last decade, the development of a number of ingenious techniques has led to the possibility of evaluating respiratory mechanics from the neonate up to children 3-4 yrs of age. Among these methods, the single-breath occlusion (SBO) technique and the multiple occlusion (MO) technique have gained extensive acceptance, and are used both in spontaneously breathing and mechanically ventilated infants. These techniques allow the assessment of the passive mechanics of the total respiratory system (compliance, resistance and time constant), by evoking the Hering-Breuer inflation reflex, which results in relaxation of both inspiratory and expiratory muscles. These methods are suitable for repeated assessment in small infants and for longitudinal studies, because of their low invasivity, high reproducibility and relatively simple application. Pulmonary function tests may represent a useful guide in diagnosis, monitoring, prediction of outcome, and management assessment in infants and children with lung diseases. However all these techniques are limited by implicit assumptions and further developments towards simpler methods are needed. PMID- 8193629 TI - The screening of obstructive sleep apnoea. PMID- 8193630 TI - Isoniazid prophylaxis of tuberculosis. PMID- 8193631 TI - Perceptual speech characteristics of dysarthric speakers following severe closed head injury. AB - The perceptual speech characteristics of a group of 20 severely closed head injured (CHI) subjects were compared with those of a normal non-neurologically impaired control group matched for age and sex. The CHI subjects were found to be significantly less intelligible than the controls, and exhibited deficits in the prosodic, resonatory, articulatory, respiratory and phonatory aspects of speech production. The most frequently occurring deviant speech dimensions related to disturbances of prosody, resonance, articulation and respiration, with those deviant speech dimensions pertaining to phonation being less apparent in the speech of the CHI subjects. The findings are discussed in relation to the heterogeneity of the CHI population and the effects of CHI on neuromuscular function. The study highlights the need for accurate, instrumental physiological evaluation of the motor subsystems involved in speech production. PMID- 8193632 TI - Visual evoked potentials (VEP) evaluating treatment for post-trauma vision syndrome (PTVS) in patients with traumatic brain injuries (TBI) AB - Post-trauma vision syndrome (PTVS), which is characterized by binocular function problems, may be caused by dysfunction of the ambient visual process which is part of the sensory-motor feedback loop rather than specific oculomotor disturbance. Clinically, PTVS frequently presents with symptoms of diplopia, blur, seeing movement in the spatial environment, vertigo, and hallucination-like experiences. Visual evoked potentials (P100) were used to evaluate an experimental group (n = 10) of subjects who suffered a traumatic brain injury, and a control group (n = 10). A new treatment using prisms and bi-nasal occluders which affected amplitude responses of the VEP was evaluated. The results demonstrate the amplitude of the VEP is a function of cortical binocular integration, and that this is influenced by dysfunction of the ambient visual process. The results also demonstrate that base-in prism and bi-nasal occluders are an effective means to treat ambient vision disturbances resulting from head trauma which causes PTVS. PMID- 8193633 TI - Affective symptoms in the chronic stage of traumatic brain injury: a study of married couples. AB - A convenient sample of 60 brain-injured subjects and their spouses was evaluated cross-sectionally in the chronic stage of recovery on self-rated measures of sensory, motor, cognitive and behavioural disability and on the SCL-90-R depression and anxiety subscales. A majority of the brain-injured subjects, who were on average almost 6 years post-injury, demonstrated elevations on the affective symptom scales, with almost 70% showing depression and 50% showing anxiety. The spouses of the brain-injured individuals also demonstrated significantly elevated affective symptom scales, with 73% acknowledging symptoms of depression and 55% demonstrating symptoms of anxiety. For the individuals with brain injury, those with higher self-ratings of cognitive disability and social aggression had higher self-ratings of depression and anxiety. In contrast, spouse gender appeared to have the greatest association with the presence of elevation affective responses, with female spouses having higher levels of depression and anxiety than male spouses. These findings are discussed in terms of the reactionary nature of affective disturbances in the chronic stage of recovery. PMID- 8193634 TI - The public perception of head injury in Missouri. AB - Head injury constitutes a significant public health concern. Despite increasing recognition of the morbidity and mortality associated with head injury, there exist few statewide estimations of the prevalence and public perception of head injury. Knowledge of the public's perception can facilitate the funding and planning for the treatment and rehabilitation of persons with head injury. This study was undertaken for this purpose by the Missouri Head Injury Advisory Council and consisted of a stratified sampling of 1123 Missourians in a statewide telephone poll. The results revealed that the general public has an accurate perception of head injury and that knowledge improved as a function of direct experience with head injury. PMID- 8193635 TI - Characteristic reactions of relatives of post-coma unawareness patients in the process of adjusting to loss. PMID- 8193636 TI - Use of the Children's Orientation and Amnesia Test at hospital discharge for children with neurological and non-neurological traumatic injuries. AB - The measurement of post-traumatic amnesia in children is a common clinical index of the extent of brain injury. The only published paediatric test, the Children's Orientation and Amnesia Test (COAT), has been standardized on a sample of children in a school setting who had not been injured or hospitalized. Two questions arise in the use of this test: are the published norms valid for hospitalized children with non-neurological trauma? and does the COAT offer better discriminative power or clinical utility over the adult test, the Galveston Orientation and Amnesia Test (GOAT)? This paper describes scores on the COAT for 28 children hospitalized with non-neurological injuries and compares them with the published scores. The hospitalized children scored within normal limits when compared with the school sample. In addition, 23 children with neurological traumatic injuries were given both the COAT and the GOAT. Failure rate was higher for the COAT. Some implications for the use of the COAT in paediatric trauma are discussed. PMID- 8193637 TI - Measuring post-traumatic amnesia (PTA): an historical review. AB - The duration of post-traumatic amnesia (PTA), which is the period following brain injury when patients are disoriented and impaired in the acquisition of new information, has been used as a behavioural indicator of the severity of injury. This paper reviews earlier retrospective and more recently developed prospective methods of assessing the duration of PTA. Prospective assessment that commences before the resolution of PTA overcomes the possible over- or underestimation of the duration of PTA inherent in methods that assess PTA retrospectively by clinical interview. PMID- 8193638 TI - Managing myoclonus secondary to anoxic encephalopathy through EMG biofeedback. AB - Biofeedback has traditionally been used in the context of relaxation therapy along with stress management. Some recent studies have looked to extend the applicability of biofeedback by using it as a didactic tool for neuromotor rehabilitation. The present case is one in which an anoxic head-injury patient was unable to participate in transfers owing to a severe myoclonic condition. The patient was trained using an autogenic relaxation procedure along with EMG biofeedback modality to reduce the myoclonus and therefore participate actively with stand pivot transfers. PMID- 8193639 TI - Metabolic engineering of plant secondary products. AB - Plants interact with their environment by producing a diverse array of secondary metabolites. Many of these compounds are valued for their medicinal, industrial or agricultural properties. Other secondary products are toxic or otherwise undesirable and can reduce the commercial value of crops. Gene transfer technology offers new opportunities to modify directly plant secondary product synthesis through metabolic engineering. This article reviews some of the strategies which have been used to increase or decrease the synthesis of specific plant metabolites, as well as methods for expanding the biosynthetic capabilities of individual species. PMID- 8193640 TI - A plant transformation vector with a minimal T-DNA. AB - Plant transformation, via Agrobacterium tumefaciens, is usually performed with binary vectors. Most of the available binary vectors contain within the T-DNA (which is transferred to the plant genome) components not required for the intended modification. These additional sequences may cause potential risks during field testing of the transgenic plants or even more in the case of commercialization. The aim of this study was to produce a plant transformation vector which only contains a selectable and screenable marker gene and a multiple cloning site for insertion of promoter::foreign gene::terminator cassettes from other plasmids. PMID- 8193641 TI - High level production of human growth hormone in the milk of transgenic mice: the upstream region of the rabbit whey acidic protein (WAP) gene targets transgene expression to the mammary gland. AB - The 5' flanking region (6.3 kb) of the rabbit WAP (rWAP) gene possesses important regulatory elements. This region was linked to the human growth hormone (hGH) structural gene in order to target transgene expression to the mammary gland. Thirteen lines of transgenic mice were produced. Milk could be collected from six lines of transgenic mice. In five of them, hGH was present in the milk at high concentrations ranging from 4 to 22 mg ml-1. hGH produced by the mammary gland comigrated with hGH of human origin. It was biologically active, and through its prolactin-like activity induced lactogenesis when introduced into mammary culture media. Two of these mouse lines were studied further. hGH mRNA was only detected in the mammary gland during lactation. In the seven other transgenic lines, hGH was present in the blood of cyclic females. The prolactin-like effect of hGH in these mice probably induced female sterility, and milk could therefore not be obtained. In two lines studied in more detail, the mammary gland was the main organ producing hGH, even in cyclic mice. Low ectopic expression was detected in other organs which varied from one line to the other. This was probably due to the influence on the transgene of the site of integration into the mouse genome. In the 13 lines studied, high mammary-specific hGH expression was not correlated to the transgene copy number. The rWAP-hGH construct thus did not behave as an independent unit of transcription. However, it can be concluded that the 6.3 kb flanking region of the rWAP gene contains regulatory elements responsible for the strong mammary-specific expression of hGH transgene, and that it is a good candidate to control high levels of foreign protein gene expression in the mammary gland of lactating transgenic animals. PMID- 8193643 TI - Will MD solo practice survive? Yes. PMID- 8193644 TI - Homeless in America. PMID- 8193642 TI - Expression of human lactoferrin in milk of transgenic mice. AB - The expression of human lactoferrin (hLF) in the milk of transgenic mice is described. Regulatory sequences derived from the bovine alpha S1-casein gene were fused to the coding sequence of the hLF cDNA and several lines of transgenic mice were generated. Human LF RNA was detected exclusively in the mammary gland of lactating females and only after the onset of lactation. No aberrant RNA products could be detected using northern blotting and primer extension analysis. The hLF concentrations in the milk ranged from less than 0.1 to 36 micrograms ml-1. Human LF thus expressed did not differ from human milk derived LF, with respect to molecular mass and immunoreactivity with monoclonal and polyclonal antibodies. PMID- 8193645 TI - Americans in the dark about hepatitis. PMID- 8193646 TI - Quality watch ... unwarranted right heart catheterizations. PMID- 8193647 TI - Medical device manufactures of raw materials want protection from liability. PMID- 8193648 TI - The Minnesota model--the pace car. In the race to integrate, the Twin Cities market leads the pack. PMID- 8193649 TI - The Minnesota model--tailgating the market. Legislative reform in Minnesota moves ahead--slowly. PMID- 8193650 TI - The Minnesota model--road work ahead. A Minnesota group aims to build a statewide information highway. PMID- 8193651 TI - CEO summit. Building the new health care delivery alliance, Part III. Roundtable discussion. AB - In cooperation with McManis Associates, Hospitals & Health Networks recently convened a CEO summit on physician/hospital integration activities. In the third report of a three-part series on the summit, leading health care executives discuss investor capital needs, strategic information management needs, and the management competencies required for capitated managed care success. PMID- 8193652 TI - Should the public have access to the National Practitioner Data Bank? PMID- 8193653 TI - A better place to be. Integrated, capitated care gives frail elderly a choice over nursing homes. PMID- 8193654 TI - An integrated system grows in Boston. Interview by Karen Gardner. AB - After news reports highlighting discussions among the major teaching hospitals in Boston last year, two leading academic medical centers--Massachusetts General Hospital (MGH) and Brigham and Women's Hospital--teamed up to form Partners Healthcare System Inc. Ferdinand Colloredo-Mansfield, the former chairman of MGH and the current co-chair of the new system, spoke recently with TRUSTEE editor Karen Gardner about the integration process now taking place between the two hospitals. Colloredo-Mansfeld, president of Cabot Partners, a real estate investment counseling firm in Boston, has been a trustee of MGH since 1982 and has served as chairman since 1992. He has also been an active participant in the process. PMID- 8193655 TI - Data watch. HMO outpatients help keep hospitals afloat. PMID- 8193656 TI - Montana hospital leads community discussion on reform. PMID- 8193657 TI - Pain relief: recent guidelines challenge current practices. PMID- 8193658 TI - Speaking the same language: group aims for CPR standards. PMID- 8193659 TI - Consumer choice could give big boost to assisted living. PMID- 8193660 TI - Parish nurse programs strengthen community links. PMID- 8193661 TI - Governance 100 survey: membership makeup of hospital boards hasn't changed much- yet. PMID- 8193662 TI - Some food for thought. PMID- 8193663 TI - Hospital resource allocation: the real story. PMID- 8193664 TI - Histochemical study of human nasopharyngeal epithelium by horseradish peroxidase conjugated lectins. AB - This study proposes a simple method for assessing whether non-respiratory epithelia of the nasopharynx (i.e. cuboidal, squamous) represent a modified differentiation from the normal pseudo-stratified lining, or whether they possess common characteristics suggesting they are just in a different morphological stage. Peroxidase-labelled lectins were used, since they detect sugar residues of membrane glycoconjugates which play an important role in cell differentiation. Biopsies were taken from healthy controls and from patients affected by upper airway inflammation of varying degree and duration. While pseudostratified and cuboidal epithelia possess similar histochemical characteristics, squamous epithelium has a different behaviour; in particular it is the only type to show intense reactivity to Lotus tetragonolobus lectin (LTA). This would seem to indicate that squamous epithelium is in a different state of differentiation, possibly suggesting dysplasia. Lectins may be valuable both in morphological studies and in the clinical evaluation of airway epithelia. PMID- 8193666 TI - Beta-receptor blockade by propranolol modifies the effect of the inhibitory, endogenous epidermal pentapeptide on epidermal cell flux at the G2-M transition but not at the G1-S transition. AB - The mitosis inhibitory pentapeptide, pGlu-Glu-Asp-Ser-GlyOH (EPP), which was isolated from mouse epidermis extracts, belongs to a group of growth inhibitory peptides that all have pyroglutamyl at the N-terminal end. Earlier experiments with crude or partially purified skin extracts have shown that the inhibitory effect could be enhanced by beta-receptor agonists and by dibutyryl cAMP, and that beta-receptor blockade could neutralise it. We now show that treatment with the beta receptor blocker propranolol before or after EPP treatment of hairless mice significantly modifies the effect of EPP on mouse epidermal cell proliferation, as estimated by using a metaphase-arrest technique (Colcemid) to estimate the G2-M cell flux. The interaction between propranolol and EPP is complex; only the EPP-induced inhibition of the G2-M cell flux was modified by beta-receptor blockade, while the late (18-21 h) inhibition of the mitotic rate was unaltered. Propranolol alone was followed by a dose-related and transient increase in the epidermal mitotic rate. The phosphodiesterase inhibitor caffeine had no effect on its own on epidermal cell proliferation but counter-acted the late (18-21 h) EPP-induced inhibition. PMID- 8193665 TI - Characterization and comparison of ion transport across sheep and human airway epithelium. AB - This study aimed to assess the suitability of sheep tracheal epithelium as a model for studies of human airway ion transport. Ovine and human airway epithelium were mounted in Ussing chambers under short circuit conditions. Bumetanide (100 microM) reduced short-circuit current (Isc) by a mean of 21.3% +/ SEM 2.0, n = 8, in sheep, and 30.4% +/- 9.7, n = 3, in human airway epithelium. Acetazolamide (100 microM) decreased Isc by 10.6% +/- 1.2, n = 18, in sheep, and 5.8% +/- 2.9, n = 3, in human airways. Phloridzin (200 microM) reduced Isc by 4.7% +/- 0.8, n = 7, and 3.1% +/- 5.1, n = 3 in sheep and human tissue respectively. Amiloride (100 microM) decreased Isc by 42.9% +/- 3.5, n = 12, in sheep airways, whilst bathing the mucosal surface with Na(+)-free solutions reduced Isc by 67.4% +/- 4.2, n = 18. The sequential addition of acetazolamide, bumetanide, phloridzin, amiloride and mucosal Na(+)-free solutions totally inhibited the basal Isc in both sheep and human tissues, suggesting that Cl- and HCO3- secretion, Na(+)-glucose co-transport and amiloride-sensitive and insensitive Na+ absorption contribute to the Isc. The similarities between the species suggest that sheep tracheal epithelium is a useful model for basal studies of airway ion transport, and may prove a valuable tool for further regulatory studies. PMID- 8193667 TI - Mitochondrial DNA sequence variation in the European sea bass, Dicentrarchus labrax L. (Serranidae): evidence of differential haplotype distribution in natural and farmed populations. AB - PCR and direct sequencing of 300 to 377-bp fragments of the cytochrome b mitochondrial gene were carried out in 40 specimens of European sea bass, Dicentrarchus labrax L., collected at different sites in the Mediterranean basin and representing wild and farmed populations. Sequence analysis revealed 6 transitional changes, which generated 5 different haplotypes (A-E). Only one mutation was nonsynonymous because it occurred in the first position of a codon leading to the replacement of valine by isoleucine. The genotypic distribution revealed that haplotype B was not present in the farm samples, whereas its frequency in the wild samples exceeded 30%. In contrast, haplotypes D and E were found in farmed populations but not in the wild populations. The comparison among wild populations showed a nonhomogeneous distribution of the two most frequent haplotypes, A and B. PMID- 8193668 TI - Cytochrome P450 1A1 cDNA from plaice (Pleuronectes platessa) and induction of P450 1A1 mRNA in various tissues by 3-methylcholanthrene and isosafrole. AB - A full length cDNA coding for cytochrome P450 1A1 was isolated from a plaice liver cDNA library constructed in lambda ZAPII. The deduced amino acid sequence of this cDNA was 78% homologous to that of rainbow trout P450 1A1 and 57 and 51% homologous to human P450 1A1 and P450 1A2, respectively. Comparisons of these sequences show the plaice cDNA to be most similar to mammalian and trout P450 1A1 sequences, but also to have certain residues specific to fish P450 1A1. Analysis of Southern blots of restriction endonuclease-digested plaice genomic DNA showed only 1 or 2 bands after hybridization to the first 800 nucleotides of the plaice cDNA, and Northern blots showed only one cross-hybridizing band in a variety of tissues, suggesting that only 1 gene and no closely related sequences were present. This evidence implies that the plaice (and trout) P450 may represent an ancestral gene to the mammalian P450 1A1 and P450 1A2 genes. A variety of plaice tissues showed increases in P450 1A1 RNA after treatment with the prototypical P450 1A family inducers (3-methylcholanthrene [3MC] and isosafrole [ISF]); the strongest response occurred in heart, with slightly less induction in kidney and intestinal mucosa. A significant induction of P450 1A1 mRNA was also observed in plaice whole blood after 3MC or ISF treatment. Liver P450 1A1 mRNA showed a relatively weak response to these inducers but did exhibit elevated microsomal EROD activities, especially in ISF-treated animals. The results are discussed with reference to the possible use of plaice P450 1A1 cDNA as a probe for environmental monitoring studies. PMID- 8193669 TI - Small subunit ribosomal RNA gene sequence of the oyster parasite Perkinsus marinus. AB - The small subunit rRNA gene of the oyster pathogen Perkinsus marinus was characterized from cells of infected oyster hemolymph by polymerase chain reaction and molecular cloning. The gene, 1,793 nucleotides in size, has 77.2% sequence similarity to that of its host, the eastern oyster Crassostrea virginica. The sequence was confirmed using recently available in vitro cultures of P. marinus. DNA from pure P. marinus culture was amplified with specific primers synthesized according to the sequence from infected oyster hemolymph, and predicted size fragments were obtained. Furthermore, restriction digests yielded fragments of expected size in amplified rDNA from in vitro cultures. The P. marinus sequence has 97.5% similarity to the Perkinsus sp. sequence from the Australian mollusc Anadara trapezia. PMID- 8193670 TI - Age-related and tissue-specific levels of five forms of insulin-like growth factor mRNA in a teleost. AB - A reverse transcriptase/PCR assay was employed to amplify an internal portion of insulin-like growth factor I (IGF I) and IGF II cDNA from the RNA of juvenile rainbow trout (Oncorhynchus mykiss) in an effort to detect analogues to the multiple size forms of IGF mRNA known to exist in mammals. After cloning and sequencing the PCR products, 4 variant size forms of trout IGF I mRNA and 1 form of IGF II mRNA were evident. The full cDNA nucleotide sequence of 1 form of IGF I mRNA and IGF II mRNA have been previously reported; the full cDNA nucleotide sequence of a second form of IGF I mRNA and PCR-derived nucleotide sequences of the 2 additional IGF I mRNA forms are reported herein. We define the 4 forms of IGF I mRNA (IGF IEa-1, Ea-2, Ea-3, and Ea-4) as having E-domain peptide lengths of 35, 47, 62, and 74 predicted amino acid residues, respectively. RNAse protection assays were used to quantify the mRNA levels of each of the 5 IGFs in 8 tissues of both juvenile and adult trout, as well as in testes and ovaries of adult trout. The IGF mRNA levels, normalized with 18S rRNA levels, suggest (1) at least 1 form of IGF I and IGF II mRNA are present at both developmental stages in all tissues examined; (2) all 5 IGF mRNA forms are present at their highest levels in the liver (p < 0.05); and (3) adults have significantly higher IGF mRNA levels than juveniles in the liver (p = 0.0047). PMID- 8193671 TI - A novel ornithine transcarbamylase present in mycoplasma-infected myeloma cells. AB - A myeloma cell line (KHM-4) from a patient with multiple myeloma and idiopathic hyperammonemia, and another myeloma cell line (RPMI8226) were seen to have activity to form ammonia from arginine. High activity of ornithine transcarbamylase (OTC), a hepatic urea cycle enzyme, was detected in these cell lines. OTC of these cells was much more heat-stable than the liver enzyme, and did not cross-react with an antibody against the liver enzyme. As the OTC activity was also detected in the culture medium of the myeloma cells and because the activity was markedly decreased by the antimycoplasma drug MC-210, the OTC activity was assumed to be associated with mycoplasma infection. Polymerase chain reaction, using degenerate oligonucleotide mixtures corresponding to the two highly conserved sequences of OTC, amplified a DNA sequence that apparently encodes a portion (about 67% in length) of mycoplasma OTC. The predicted amino acid sequence of the mycoplasma enzyme was 33-47% identical with those of the enzymes of bacteria, yeast and mammals. PMID- 8193672 TI - Postnatal expression of hypoxanthine guanine phosphoribosyltransferase in the mouse brain. AB - The distributional and activity changes of hypoxanthine guanine phosphoribosyltransferase (HGPRT) were investigated in the developing mouse brain. The HGPRT activity level was low at birth, increased rapidly during the first 7 days of life, and underwent a gradual increase thereafter to the mature level. Polyclonal antibody against HGPRT purified from mouse brain was prepared for immunohistochemical demonstration of the enzyme during brain development. In the cerebellum, part of the Purkinje cells was consistently immunostained throughout growth, and the presence of HGPRT was observed in the dendrites of mature Purkinje cells. The most dominant change in HGPRT localization was observed in the hippocampus. Little HGPRT was detectable in the newborn mouse hippocampus. At postnatal day 7, cytoplasmic HGPRT appeared sporadically in the granular cells independently of the region of the hippocampus. The number of positive immunoreactive cells increased with growth, and the dendrites of granular cells were also immunostained on postnatal day 28. Further immunostaining was noted in the granule cells of the dentate gyrus on postnatal day 35. The above results suggest that HGPRT may play an important role in the developing hippocampus. Further investigations of the HGPRT in the human hippocampus may help to clarify the mechanism underlying the neurological disorders encountered in the Lesch-Nyhan syndrome. PMID- 8193673 TI - Characterization of the alkaline phosphatase expressed on the surface of a Hodgkin's lymphoma cell line. AB - Alkaline phosphatase solubilized from a human Hodgkin's lymphoma cell line (L428) was compared with purified amphiphilic and hydrophilic forms of the enzyme from human liver, and with the enzyme solubilized from a cultured osteosarcoma cell line (Saos-2). Purified hydrophilic alkaline phosphatases from human placenta and intestine were also compared in some experiments. Alkaline phosphatase was released from the plasma membrane of intact lymphocytes by phosphatidylinositol phospholipase C and thus is anchored to the outside of the plasma membrane by covalently attached phosphatidylinositol. Enzyme released in this way was hydrophilic and that solubilized with Triton X-100 was amphiphilic, as assessed by adsorption to octyl-Sepharose. Lymphocyte alkaline phosphatase, when released from the membrane by phosphatidylinositol phospholipase C or solubilized by Triton X-100, had apparent M(r) values on gradient gel electrophoresis of 227 and 494 kDa, respectively. These values were consistently higher than equivalent ones obtained with enzymes purified from human liver, but were similar to those of cultured osteosarcoma cells. Isoenzyme-specific inhibitors of alkaline phosphatase showed similar patterns of inhibition between the enzyme from L428 cells and the tissue-nonspecific (liver/kidney/bone) isoenzyme from human liver. Heat stabilities were similar for the enzymes from L428 and Saos-2 (bone isoform) cell lines, but differed significantly from those of liver, intestine and placenta. We conclude that the alkaline phosphatase expressed in this lymphoma cell line (L428) has properties that most closely resemble those of the tissue nonspecific isoenzyme found normally in osteoblasts of bone (bone isoform). PMID- 8193674 TI - 11-beta-Hydroxysteroid dehydrogenase of rat lung: enzyme kinetic, oxidase reductase ratio, electrolyte and trace element dependence. AB - The modulation of the intracellular glucocorticoidal effect on surfactant synthesis of the fetal lung by the metabolic capacity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) could be an important factor in lung maturation. The kinetic properties of microsomal 11 beta-HSD of the rat lung are characterized with respect to product inhibition, substrate specificity, effect of electrolytes or trace elements, and the dependence of the oxidase reductase (OR) ratio on incubation conditions. With NADP+ product inhibition of the reductase was demonstrated. The most common trace elements and electrolytes exhibited no effect on the activity of 11 beta-HSD. It is shown that the OR ratio was strongly dependent on assay conditions. With optimal assay conditions oxidase activity exceeds reductase activity in adult and fetal rat lung microsomes (OR ratio > 1). Thus, glucocorticoids are mainly metabolized to their inactive forms. The enzyme activity in the adult is about 10 times higher than in the fetal lung. The low enzyme activity in fetal lungs could be the reason why the glucocorticoidal effects on surfactant synthesis are not suppressed despite the predominance of oxidase activity. PMID- 8193675 TI - Purification and characterization of a glutathione peroxidase from the Aloe vera plant. AB - Extracts from the parenchymous leaf-gel of the Aloe vera plant (Aloe barbadensis Miller) were shown to contain glutathione peroxidase (GSHPx) activity. The activity was purified to homogeneity by ion exchange and gel filtration (FPLC) chromatography in the presence of 0.5 mM glutathione. The native enzyme has an apparent molecular weight of 62 kD as determined by gel filtration. In the presence of sodium dodecylsulfate (SDS), the molecular weight was estimated to be about 16 kD as determined by polyacrylamide-gel electrophoresis (SDS-PAGE). The native enzyme is proposed to be constituted of four identical subunits; it also contains one atom of selenium per subunit, as found with most glutathione peroxidases from animal sources. The Km values were determined to be 3.2 mM for glutathione and 0.26 mM for the hydroperoxide substrate, cumene hydroperoxide. The enzyme is competitively inhibited by N, S, bis-FMOC glutathione (Ki = 0.32 mM), a potent inhibitor of glyoxalase II. Inhibitors of glyoxalase I (e.g. S octylglutathione) have no effect on the peroxidase activity. PMID- 8193676 TI - Regulation of rat-renal cortex phosphofructokinase activity by pH. AB - The activity of phosphofructokinase purified from rat kidney cortex has been assayed at two different pH values. At pH 7 the enzyme showed cooperativity for the binding of fructose 6-phosphate (Fru-6-P) and a strong allosteric inhibition by ATP. When the assays were done at pH 8 hyperbolic kinetics were observed for both substrates, a smaller inhibition by ATP was observed and the Vmax for ATP and for Fru-6-P was higher than at pH 7. A sequential reaction mechanism was inferred. Results are discussed in terms of the importance of a reduced hexose phosphate cycling rate during metabolic acidosis induced by exercise. PMID- 8193677 TI - Health promotion and disease prevention. Call for papers. PMID- 8193678 TI - Weight perceptions and weight control practices in American Indian and Alaska Native adolescents. A national survey. AB - OBJECTIVE: To assess weight perceptions and weight control practices among American Indian-Alaska Native adolescents. DESIGN: Survey. SETTING: Nonurban schools from eight Indian Health Service areas. PARTICIPANTS: A total of 13,454 seventh- through 12th-grade American Indian-Alaska Native youths. MAIN OUTCOME MEASURES: A revised version of the Adolescent Health Survey, a comprehensive, anonymous self-report questionnaire with eating- and body image-related questions. RESULTS: Forty-one percent of the adolescent girls reported feeling overweight, 50% were dissatisfied with their weight, and 44% worried about being overweight. Almost half (48%) had been on a weight-loss diet in the past year, with 27% reporting that they had self-induced vomiting at some time to try to lose weight. Eleven percent reported using diet pills. Girls who reported feeling overweight were more likely to engage in unhealthy weight control practices than were those who felt they were of normal weight or underweight. A larger proportion of boys were satisfied with their weight (68%), with 22% worrying about being overweight. However, compared with rural Minnesota youth, both American Indian girls and boys had greater dissatisfaction with body weight. CONCLUSIONS: Our study shows that American Indian youth, particularly girls, are dissatisfied with their weight and are worried about being overweight, and that unhealthy weight control practices are common. More attention needs to be placed on developing culturally appropriate weight management programs for Indian youths. PMID- 8193679 TI - The Larimer County Children's Clinic. A public-private partnership to provide medical care to indigent children. AB - OBJECTIVE: To describe a unique collaboration between private and public entities to provide comprehensive health care to medically indigent children in rural Larimer County, Colo. SETTING: The Children's Clinic, Fort Collins, Colo. STUDY PARTICIPANTS: Uninsured children and those eligible for Medicaid, living in families with incomes below 150% of the federal poverty level. SELECTION PROCEDURES: Eligible patients have been enrolled in the Children's Clinic on a first-come, first-served basis. INTERVENTIONS: A community collaboration involving an interactive system with the Children's Clinic staff, the Larimer County Department of Health and Environment, private primary care and subspecialty physicians, ancillary health providers, and the family practice residency program at Poudre Valley Hospital, Fort Collins. Funding for this endeavor has been composed of city and county funds, public and private grants, community business support, and local fund-raising efforts, as well as Medicaid reimbursements. MEASUREMENTS/MAIN RESULTS: Since 1989, comprehensive pediatric care has been provided to a growing number of eligible children. At present, 3619 children, aged birth to 18 years, from 2230 families are being served. From this population, there were 8945 office visits to the Children's Clinic, 1392 patient contacts by the clinic social workers, 1287 visits to the Larimer County Department of Health and Environment for well-child care, 543 referrals to subspecialists and other community health care providers, and 615 after-hours visits to the Poudre Valley Hospital emergency department between July 1, 1992, and June 30, 1993. The clinic's professional staff consists of 2 1/4 full-time pediatric care providers, one nurse, one medical social worker, one receptionist, and one administrator, with an expenditure of $356,471. CONCLUSIONS: The Children's Clinic collaboration has provided comprehensive pediatric health care to a population that previously received only fragmented care. The next step is to assess the impact of this program on the frequency of emergency department visits for these patients. PMID- 8193680 TI - Full-time attending physician coverage in a pediatric emergency department. Effect on risk management. AB - OBJECTIVE: To determine the effect on risk management of full-time attending physician coverage in a pediatric emergency department. DESIGN: Retrospective, with data collected through a review of malpractice cases from August 1, 1984 through July 31, 1990. SETTING: Large urban teaching hospital's pediatric emergency department. RESULTS: Malpractice cases from August 1, 1984 to July 31, 1987, when there was part-time attending physician coverage, were compared with those of 1987 through 1990, when full-time attending physician coverage was instituted. Medical records from the pediatric emergency department, subsequent hospital records, and abstracts of claims were reviewed. Disbursements and the types of lawsuits were also analyzed. There was a 41.7% decrease in the number of claims filed and a 44.3% reduction in payments with full-time coverage. CONCLUSIONS: Full-time attending physician coverage in a pediatric emergency department was associated with a decrease in the number of malpractice claims and the amounts of disbursements. Further research in this area on a larger study sample is advisable. PMID- 8193681 TI - Recombinant human erythropoietin vs transfusions in the treatment of anemia of prematurity. A cost-benefit analysis. AB - OBJECTIVE: To evaluate the costs relative to the benefits of using recombinant human erythropoietin (rHuEPO) therapy as an alternative to red blood cell (RBC) transfusions in infants with anemia of prematurity. DESIGN: A cost-benefit analysis of rHuEPO therapy was performed based on its use in very-low-birth weight premature infants. SETTING AND PATIENTS: Data were drawn from published studies or were provided by the University of Iowa Hospitals and Clinics, Iowa City. MAIN OUTCOME MEASURES: Costs and benefits were analyzed as a comparison of incurred costs to averted costs. Incurred and averted costs of rHuEPO therapy and RBC transfusions included direct product costs and estimates of costs of adverse events. The analysis was viewed in terms of net savings. Sensitivity analysis was performed. RESULTS: The base case analysis yielded a net loss of $299.48 per infant. A 54% reduction in the direct product costs of rHuEPO therapy yielded a break-even point. No other variations in the sensitivity analysis resulted in a net savings. CONCLUSION: Using assumptions based on the current state of clinical research, it appears that routine use of rHuEPO with supplemental RBC transfusions would not generate any cost savings as an alternative to RBC transfusions alone. As further evidence is compiled on the efficacy of rHuEPO therapy in very-low-birth-weight premature infants, the true costs may be better established. PMID- 8193682 TI - Initial presentations of pediatric hemophiliacs. AB - OBJECTIVE: To examine the manner of presentation and time elapsed before diagnosis in a current population of pediatric patients with coagulopathies compared with a historically similar group presented by Baehner and Strauss in 1966. DESIGN: Comparative retrospective patient series. SETTING: A large pediatric (hemophilia) referral center in New York, NY. POPULATION: Sixty-five male patients presented for evaluation of a presumed coagulopathy between 1974 and 1989. Nine patients were excluded for inadequate data or follow-up. Of the 56 patients included, 47 were were factor VIII deficient (32 severely affected, 15 not severely affected) and nine were factor IX deficient (six severely affected, three not severely affected). INTERVENTIONS: None. RESULTS: Severely affected neonates were diagnosed younger than 1 month significantly more often in this patient population compared with the 1966 population (68.4% vs < 10%, P < .001). Patients not severely affected were also diagnosed younger than 1 month significantly more often than in 1966 (50% vs 2.5%, P < .001). Workup in these groups was initiated because of either bleeding events or family history with similar frequency (48.6% vs 51.4%); historically, diagnosis had ensued primarily after bleeding events. By 1 year of age, all severely affected infants had been diagnosed in our population, a statistically significant improvement compared with the historical group (100% vs < 40%, P < .001); patients not severely affected were also diagnosed more frequently (72.2% vs 15%, P < .001). Eighty five percent of diagnoses made after 1 month of age were based on bleeding events, despite a positive family history of 28.6%. Overall, 35.7% of diagnoses resulted after a positive family history was elicited. CONCLUSIONS: In this population, diagnoses were made earlier than in the comparison group. Attention to family history and early bleeding events continues to contribute to the early diagnosis of factor deficiencies. PMID- 8193684 TI - Radiological case of the month. Familial pheochromocytoma. PMID- 8193683 TI - Implementation of a physician education intervention. The Childhood Asthma Project. AB - OBJECTIVES: To increase pediatric residents' knowledge of the Guidelines for the Diagnosis and Management of Asthma (GDMA) developed by the Expert Panel of the National Asthma Education Program and to increase the residents' confidence in their ability to implement these guidelines. Emphasis was placed on the diagnosis and treatment of Hispanic children with asthma, a population at increased risk for morbidity. SETTING: A continuity care clinic located in an urban ambulatory care facility. SUBJECTS: Forty-four pediatric residents: 17 first-year residents, 15 second-year residents, and 12 third-year residents. METHODS: Residents participated in a multicomponent asthma management curriculum that stressed active learning strategies, including the following: focus groups, computer-based testing, lectures, hands-on skill development seminars, role modeling by attending pediatricians, provision of GDMA pocket cards and posters, access to peak flowmeters and spirometry, and an interactive computer-based module. Content focused on pulmonary function testing with spirometry and peak flowmeters, stepwise use of medications, recognition of asthma symptoms and triggers, and cultural considerations that impact asthma management. Pediatric faculty and fellows also participated in a series of asthma seminars to increase the likelihood that faculty would role model the GDMA and provide appropriate feedback to residents. RESULTS: Pediatric residents demonstrated significant increases in knowledge about evaluation of asthma, pulmonary function testing, and clinical management, displayed significantly enhanced levels of confidence, and were enthusiastic about the asthma management curriculum, rating it significantly higher than 15 other content areas in the general pediatric curriculum. PMID- 8193685 TI - Radiological case of the month. Sinus pericranii. PMID- 8193686 TI - Picture of the month. Lymphangioma circumscriptum. PMID- 8193687 TI - Pathological case of the month. Menetrier's disease with cytomegalovirus gastritis. PMID- 8193688 TI - Pathological case of the month. The use of fluorescence in situ hybridization technique to confirm an interchromosomal insertion. PMID- 8193689 TI - Intraosseous adenosine. As effective as peripheral or central venous administration? AB - OBJECTIVE: The purpose of this study was to determine if intraosseous administration of adenosine is effective and, if so, to establish therapeutic dosage criteria for the intraosseous route compared with peripheral or central intraosseous route compared with peripheral or central venous routes. RESEARCH DESIGN: Randomized, unblinded, cross-over, within-animal control study. SETTING: University hospital in Ohio. SUBJECTS: Thirty newly weaned piglets. SELECTION PROCEDURE: Consecutive sample. INTERVENTIONS: Thirty newly weaned pigs were transesophageally (n = 26) or transvenously (n = 4) paced at a cycle length that was 10% longer than the Wenckebach threshold. The minimum effective dose of adenosine necessary to induce atrioventricular block during pacing was recorded for peripheral venous, central venous, and intraosseous routes. MEASUREMENTS AND RESULTS: The baseline resting heart rate and Wenckebach thresholds were not statistically different between subjects or between different routes of administration. The intraosseous route required a minimum effective dose of 127 micrograms/kg. Using a log transformation, the difference between central venous and peripheral venous doses was found to be statistically significant. The intraosseous dose was not statistically different from the central venous or peripheral venous doses. CONCLUSION: The intraosseous route is an effective way of administering adenosine. The peripheral venous dose required to achieve atrioventricular block is higher than the central venous dose and the intraosseous dose is intermediary to the central venous and peripheral venous doses. PMID- 8193690 TI - Clinical comparison of the Haemophilus influenzae type B polysaccharide diphtheria toxoid and the oligosaccharide-CRM197 protein vaccines in infancy. AB - OBJECTIVE: To compare two Haemophilus influenzae type B (HiB) conjugate vaccines, a polysaccharide-diphtheria toxoid conjugate (PRP-D) vaccine and an oligosaccharide-CRM197 protein conjugate (HBOC [PRP-CRM]) vaccine, in the same population. DESIGN: One hundred twenty-five thousand infants were randomized to receive the PRP-D or HBOC vaccine. Primary immunization consisted of two doses of either vaccine administered at 4 and 6 months and a booster dose was given at 14 to 18 months. Protection was assessed by recording episodes of invasive disease with HiB isolated from the blood or another normally sterile body site. SETTING: One thousand thirty-six child health care centers in Finland. PARTICIPANTS: Infants born in Finland during the 24-month period from 1987 to 1989. INTERVENTION: Each vaccine dose was injected intramuscularly in a volume of 0.5 mL. At the same time, a separate site was injected with the diphtheria and tetanus toxoids and pertussis vaccine at 4 months of age, with inactivated poliovirus vaccine at 6 months of age, and with measles-mumps-rubella vaccine at 14 to 18 months of age. MAIN RESULTS: The mean anticapsular antibody concentration 1 month after the second dose was 0.63 micrograms/mL and 4.32 micrograms/mL in the PRP-D and HBOC vaccine recipients, respectively. The booster dose resulted in a high antibody concentration: 33.3 micrograms/mL and 58.3 micrograms/mL for PRP-D and HBOC vaccine recipients, respectively. At 36 months of age, the antibody concentration declined to 2.5 micrograms/mL and 5.6 micrograms/mL for PRP-D and HBOC vaccine recipients, respectively. After two doses of the vaccine, there were five episodes (39 were expected based on historical controls) of invasive HiB disease in the PRP-D group and two episodes (35 were expected) in the HBOC group. Hence, an 87% (95% confidence limit [CL], 69, 96) protection rate in the PRP-D group and a 95% (95% CL, 76, 99) protection rate in the HBOC group were achieved. No episodes occurred after the booster dose in either group. CONCLUSIONS: Both the PRP-D and HBOC vaccines are safe and effective. A two-dose primary vaccination schedule seems appropriate, at least in circumstances prevailing in Finland and probably in other areas with similar epidemiological effects of HiB disease. PMID- 8193691 TI - Congenital diaphragmatic hernia in Minnesota. Impact of antenatal diagnosis on survival. AB - OBJECTIVE: We characterized the natural history and true mortality of congenital diaphragmatic hernia (CDH) in newborn patients by identifying all infants born with this condition in a fixed geographic region over a 2-year period. We examined this population to determine the frequency of intrauterine diagnosis, the outcome of prenatally diagnosed infants, and the impact of deaths in infants with an unsuspected diagnosis (the "hidden mortality") on the overall outcome of this condition. DESIGN: This was a retrospective population survey of all infants born with CDH in Minnesota between June 1988 and June 1990. SETTING: All Minnesota birth and death records were reviewed to identify patients with the diagnosis of CDH. A separate survey of all level 3 intensive care nurseries was conducted and the record of each identified patient was reviewed. Extracorporeal membrane oxygenation was available throughout the study period. MAIN OUTCOME MEASURE: Survival to hospital discharge and short-term morbidity were examined for each patient. RESULTS: Survival was 60% (29/48). Eleven of 19 deaths occurred in patients born prematurely and/or with coexisting major anomalies. Eight percent (4/48) of patients died within the first hour of life prior to diagnosis (hidden mortality). Intrauterine diagnosis of CDH was made in 15 patients. Survival was 60% (9/15) in infants whose conditions were diagnosed in utero, a rate identical to that for infants whose conditions were diagnosed in the postnatal period (61% [20/33]). There was no relationship between age at fetal diagnosis and mortality. CONCLUSIONS: The hidden mortality of CDH was low. Almost half of the total mortality for CDH was associated with coexisting, additional anomalies. Patients who were not offered extracorporeal membrane oxygenation owing to prematurity, other major anomalies, or birth at a center that did not offer extracorporeal membrane oxygenation accounted for 84% (16/19) of deaths. These data will be useful for determining the impact of new therapeutic strategies on the mortality of CDH. PMID- 8193692 TI - Cystic fibrosis carrier screening in a high-risk population. Participation based on a traditional recruitment process. AB - OBJECTIVE: Recent advances in molecular genetic (DNA) technology have permitted identification of previously undetectable cystic fibrosis (CF) carriers. Although research has been initiated in the general population, to our knowledge no published studies have looked at the utilization of DNA-based carrier screening in the high-risk CF population (family history of CF). DESIGN: Cross-sectional, diagnostic open trial. SETTING: Carrier testing was offered to a high-risk CF population via adult patients with CF or parents of pediatric patients with CF attending two regional CF clinics over a 3-year period. PARTICIPANTS: Consecutive sample of virtually all patients with CF (n = 118) from a population of 1 million. MAIN RESULTS: Despite free services, written follow-up, and counseling for 99% of patients attending the CF clinic, there was less than 10% participation from high-risk family members (168 blood relatives and 26 spouses of identified carriers or patients with CF; 38 and 156 persons from the adult and pediatric clinic families, respectively). Nevertheless, we identified 91 CF carriers among the 168 high-risk relatives. This is comparable to the number of carriers detected in general population carrier screening that has tested substantially more individuals (> 3000 per study). CONCLUSIONS: Our results suggest that research concerning CF carrier screening not only focus on data about fundamental program resources and numbers of carriers detected but also investigate how information about the availability of carrier screening is disseminated, the motivation behind testing, and the perceived relevance of test results by those tested in the high-risk population. These issues are increasingly relevant as screening becomes feasible using DNA testing for far more prevalent disorders (such as breast cancer and diabetes). PMID- 8193693 TI - Markedly reduced mortality associated with corticosteroid therapy of Pneumocystis carinii pneumonia in children with acquired immunodeficiency syndrome. AB - BACKGROUND: Pneumocystis carinii pneumonia is a common opportunistic infection in pediatric acquired immunodeficiency syndrome (AIDS). Mortality rates of 34% have been reported for the acute infection, with much higher mortality rates occurring in the presence of respiratory failure. Corticosteroids reduce the morbidity and mortality in adults with AIDS and P carinii pneumonia. We report herein our experience with corticosteroids in P carinii pneumonia in pediatric AIDS. METHODS: When the data on adults were published, we began treating our patients with corticosteroids. We compared these children (group 1) with those children treated in a similar manner, but without corticosteroids (group 2). RESULTS: The two groups had similar ages, initial serum lactate dehydrogenase levels, and initial alveolar-arterial difference in partial pressure of oxygen. There was a significant (P < .001) reduction in the need for mechanical ventilation and in mortality in the corticosteroid-treated group. CONCLUSION: Corticosteroid therapy during acute infection with P carinii in young children with AIDS appears to significantly reduce morbidity (as measured by the need for mechanical ventilation) and mortality. PMID- 8193694 TI - Readability of the childhood immunization information forms. AB - OBJECTIVE: To compare the reading level required to understand childhood immunization information forms with the reading grade level of an inner-city parent/caretaker population. DESIGN: Descriptive study (parents/caretakers). SETTING: Inner-city pediatric clinic. PARTICIPANTS: One hundred fifty English speaking, low-income parent/caretakers. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: The reading level of our parent population ranged from grades 2.9 to 13.3, with a median grade level of 6.90. The reading levels required for the three vaccine information pamphlets issued in 1992 by the Centers for Disease Control and Prevention (Atlanta, Ga) averaged 11.1 (approximately at the level of a high school junior). Eighty-six percent of our parents/caretakers did not have a reading level sufficient to cope with the easiest of the forms. CONCLUSIONS: The vaccine information pamphlets require a reading level beyond the capability of the vast majority of our parent population. Therefore, the goal of informed consent clearly is not being met. PMID- 8193695 TI - Conservative treatment of the scoliotic and kyphotic patient. Brace treatment and other modalities. AB - Although various forms of nonoperative treatment have been applied to spinal deformities over the centuries, it was the development of the original Milwaukee brace, a cervicothoracic-lumbosacral orthosis (CTLSO), by Blount and Schmidt in the middle 1940s that heralded a new era of nonoperative treatment and that has led to much of the success we enjoy with nonoperative treatment today. Furthermore, as our understanding of the natural history of scoliosis has grown and our recognition of the specific genetic, curvature-related, or neurophysiological factors that predispose patients to curvature progression has improved, so has our ability to successfully treat patients by nonoperative means. PMID- 8193696 TI - How to improve teaching on the hospital wards. PMID- 8193697 TI - Hypoplastic pancreatic duct and recurrent pancreatitis in a child. PMID- 8193698 TI - Recurrent attacks of scarlet fever. PMID- 8193699 TI - Alternative sources of calcium. PMID- 8193700 TI - Goat's milk is for kids: how about cow's milk? PMID- 8193701 TI - Brain tumors in patients with Fanconi's anemia. PMID- 8193702 TI - [An analysis of chromosome aberrations and SCE in children from radiation contaminated regions of Ukraine]. AB - About a two years later after the reactor accident in Chernobyl we carried out a three-year cytogenetical study of children, dwelling in two regions of Ukraine where the radiation fallout occurred. Chromosome analyses of these individuals have shown a significant increase of the frequency of aberrant cells and chromosomal type aberrations in comparison to the control. We have discovered the increase of the level of chromosomal type aberrations, extension in spectrum of complicate aberrations of chromosome (dicentrics, rings and exchange aberrations) with the years and the increase with the years a share of children with various chromosomal abnormalities. Analyses of sister chromatid exchanges (SCE) and a replication index (RI) show a significant increase of RI meaning with the years in comparison to the control. The SCE frequency didn't altered as compared to the control during different years of investigation. PMID- 8193703 TI - [The comparative radioresistance of chronically irradiated populations of Arabidopsis]. AB - The radioresistance of seeds of populations of Arabidopsis thaliana (L.) Heynh. growing for 5 years in the regions with different levels of radioactive contamination within 30 km zone of Chernobyl NPP was studied. The analysis of comparative radiosensitivity by root test was performed. It has been shown that plants from Arabidopsis population growing under chronic irradiation did not gain an increased radioresistance. The data obtained show that they are more radiosensitive. PMID- 8193704 TI - [The effect of inhibitors of DNA and protein synthesis on the chromosome aberration yield in a human lymphocyte culture exposed to gamma and neutron irradiation at different stages of the mitotic cycle. The cytogenetic effects in the G0 phase]. AB - The effect of inhibitors of protein synthesis, cycloheximide (CH), and DNA synthesis, hydroxyurea (OU) in combination with 5-fluoro-2-deoxyuridine (OU + FDUR), on the yield of chromosome aberrations in cultured human lymphocytes induced by gamma- and neutron irradiation with doses of 1 and 2 Gy in G0 phase of mitotic cycle has been studied. The inhibitors added immediately after gamma irradiation have caused reliable increase of aberration rate (CH at both doses and OU + FDUR at a dose of 2 Gy only). Both inhibitors caused no effect being added after 1.5, 3 and 5 hr after gamma-irradiation. The chromosome aberration rate substantially increased at both doses of neutron irradiation for both inhibitors added at all studied time intervals after exposure. Chromosome exchange aberrations have most contributed to the increase of aberration rate. PMID- 8193705 TI - [The content of metallothioneins in mouse bone marrow and liver and in human lymphocytes after whole-body gamma irradiation]. AB - The increase in the content of bone marrow and hepatic metallothioneins (MT) in mice with the maximum at 30 hr after whole-body gamma irradiation was shown. The MT level in that tissues at that time correlated with the exposure dose. The MT content in lymphocytes of patient with acute lympholeucosis was increased after fractionated whole-body irradiation, that index also correlated with accumulated exposure dose. PMID- 8193706 TI - [The effect of x-ray irradiation on UDP glucuronyltransferase activity in the liver microsomes of rats]. AB - It was shown that X irradiation of male and female rats with dose of 7 Gy causes phase alterations of UDP-glucuronyltransferase activity (p-nitrophenol glucuronidation was analysed) in liver microsomal fraction: 24 hr after irradiation decrease (to 45.7 +/- 6.4 and 60.2 +/- 8.6% of norm correspondingly) followed by 72 hr after irradiation increase (to 190.5 +/- 4.8 and 155.4 +/- 12.2% of norm) and normalization of the enzyme activity 120-168 hr after irradiation. Direct dependence of the 24 hr after irradiation enzyme activity decrease on exposure dose (for males in the dose range of 2-10 Gy, for females in the range of 5-12 Gy) due to reducing of active form of UDP-glucuronyltransferase (UDPGT) was established. It was found that glucuronyltransferase activity increase 72 hr after irradiation occurred against the background of normalization of UDPGT active form level. PMID- 8193707 TI - [The role of ligands in the effect of exposure to ionizing radiation on Ca2(+) ATPase and Mg2(+)-ATPase]. AB - The change of Ca(2+)-ATPase and Mg(2+)-ATPase activity in plasma membranes of thymocytes irradiated with doses of 10(2), 10(3) and 10(4) Gy in the presence of Ca2+, Mg2+ and ATP was studied. Stabilizing effect of Ca2+ and Mg2+ on Ca(2+) ATPase and ATP on Mg(2+)-ATPase under irradiation was established. PMID- 8193708 TI - [The peroxidation of pulmonary surfactant lipids in the postradiation period]. AB - In experiments with Wistar female rats it has been shown that an acute whole-body gamma irradiation with doses of 2 and 7 Gy initiates lipid peroxidation in pulmonary surfactant (Sf). Increase in the level of lipid peroxidation products in Sf (hydroperoxides and TBA-active products) was observed during 2 months. Decrease in enzymatic activity of superoxide dismutase and glutathione reductase was occurred in the first hours reaching the minimum on days 7-14 after irradiation period. In animals exposed to dose of 0.5 Gy the normalization of the indices under study was observed on 30th day. The findings demonstrate a destructive effect of lipid peroxidation on pulmonary Sf at the average and lethal exposure doses. PMID- 8193709 TI - [Hemopoiesis stimulation by low-intensity laser radiation in acute radiation sickness exacerbated by thermal trauma]. AB - In experiments with gamma-irradiated (dose of 7.0 Gy) and burned (III-B grade, 10% skin injury) hybrid mice the haemopoietic effect (1.5-2-fold increase) of low intensity laser irradiation (LILI) has been detected. At the same time there was no effect of LILI on normal animals. PMID- 8193710 TI - [The development and testing of an MTT method for assessing the reaction of peripheral blood lymphocytes to irradiation]. AB - The semiautomatic MTT assay for evaluation of differences in the reaction of human donors' peripheral blood lymphocytes to ionizing radiation was developed. The stimulation conditions and period of cultivation were determined, and redox activity of lymphocytes and their coefficient of stimulation after irradiation with different doses were defined. PMID- 8193711 TI - [The production of IL-1, IL-3 and CSA by bone marrow nuclear elements during the recovery of bone marrow hematopoiesis after lethal irradiation and the transplantation of syngeneic bone marrow]. AB - The production of haemopoietic factors (IL-1, IL-3, CSA) by adherent and nonadherent cells of lethally irradiated CBA mice bone marrow and after syngenic myelokaryocyte transplantation was studied. Radioresistant myelokaryocytes capable to produce haemopoietic factors IL-1, CSA as early as 24 hr after irradiation were found in adherent cell fraction. The synthesis of humoral factors (IL-3, CSA) by nonadherent bone marrow elements was realised in a late terms of experiment (3-6 days) that was connected with forming of functionally valuable cell forms from transplanted or viable stem cells. PMID- 8193712 TI - [The reaction of blood lymphocyte dehydrogenases after the incorporation of 131I and 137Cs radionuclides]. AB - The data on the activities of dehydrogenases in rat blood lymphocytes 30, 90, 180 and 365 days after separate and combined effect of 131I (dose of 2.5 MBq/kg) and 137Cs (dose of 1.6 Mbq/kg) are presented. It has been shown that incorporation of 131I causes intensification of redox processes which is due to structure functional disturbance in the thyroid gland. 137Cs markedly influenced the activity of some dehydrogenases in partial steps of post-irradiation development. The changes in the enzyme activities at the combined action of radionuclides are similar in many respects to data obtained in the case of 131I individual action. PMID- 8193713 TI - [The influence of diamide on the realization of the radioprotective effect of beta-mercaptoethylamine in the postradiation period]. AB - In the experiments with Ehrlich ascites tumor cells it was shown that specific oxidation of cellular glutathione after irradiation produced no effect on the degree of radiation injury in the air, but resulted in a decrease of radioprotective effect of beta-mercaptoethylamine. From these results it follows that for a complete realization of radioprotective effect normal level of cellular glutathione is necessary. PMID- 8193714 TI - [The effect of translam on the natural resistance indices of the irradiated organism]. AB - It has been studied the influence of translam-beta-1,3; 1,6-glucan, extracted from seaweed Laminaria, on the isolation of E. coli from spleen and on the functional activity of peritoneal macrophages of sublethal irradiated and infected mice. It has been shown the reduction of the number of microbes, isolated from spleen and stimulation of ingestive and digestive activity of macrophages following the introduction of translam in mice. This results show about the increase of natural resistance of irradiated organism under translam action and characterise this glucan as effective stimulator of immunity. PMID- 8193715 TI - [Pro-oxidant and antioxidant homeostasis in guinea pigs following fractionated x ray irradiation at low doses and the correction of disorders with an antioxidant complex]. AB - The state of pro-oxidant-antioxidant homeostasis in guinea pigs exposed to whole body fractionated X irradiation (5 fractions of 0.2 Gy at a 24 hr interval, up to total dose of 1.0 Gy, at a dose rate of 0.425 R/min) and a possibility of its disturbance correction with the complex of vitamins C, E and P was studied. Accumulation of primary and secondary lipid peroxidation products, decrease of the ascorbic acid content, increase of the content of its oxidized forms (dehydroascorbic acid and diketogulonic acid) in radiosensitive (spleen and small intestine) and radioresistant organs were found. Antioxidant complex administration reduced the disturbances of pro-oxidant-antioxidant homeostasis, but did not provide complete normalization. PMID- 8193716 TI - [The effect of different doses of ionizing radiation on the functional activity and mechanisms of the activation of the lymphoid cells from the spleen and thymus of rats exposed to a stimulating signal]. PMID- 8193717 TI - [The effect of chronic preliminary irradiation on the latent damages induced by single acute gamma irradiation in rats]. AB - The estimation of latent injury in rat liver under combined protracted and acute irradiation was made. It has been shown that protracted pre-irradiation did not augment resistance of liver cells to consecutive acute irradiation. On the contrary, cumulated latent injury intensifying with pre-irradiation dose rate increasing was found. PMID- 8193718 TI - [The radioecological problem of radon]. AB - Radon and its daughter decay products are the main part of natural radiation background. The review presents the information on indoor radon radiation level, radon sources, exposure doses and effects on human health. In addition to radioecological aspects, the radon effects should be considered as the important problem of low-dose radiation biology. PMID- 8193719 TI - [The comparative characteristics of the transmembrane ionic currents and the caffeine-induced responses of the smooth-muscle cells in the normal jejunum and under ionizing radiation exposure]. AB - A comparative investigation of transmembrane ion currents and caffeine-induced responses of single smooth muscle cells isolated from the circular layer of rat small intestine was carried out by the method of "patch-clamp". No reliable difference in potential-dependent and amplitude-kinetic characteristics of transmembrane ion currents in cells of intact and irradiated with dose of 3 Gy rats was revealed. In cells of irradiated animals external application of caffeine (4 mM) was not accompanied by strong quick-inactivated transient Ca(2+) dependent potassium current as in control. The results obtained suggest that single whole-body X-ray irradiation with dose of 3 Gy does not lead in 5 days to any reliable alteration of potential-controlled channels of rat small intestine smooth muscle cell plasma membranes causing at the same time the disturbance of Ca-binding function of intracellular pools. PMID- 8193720 TI - [Changes in the spinal cord potentials of the rat in whole-body irradiation at a dose of 360 Gy]. AB - In acute experiments in rats the effect of the whole-body X-irradiation with a dose of 360 Gy on induced somatosensory spinal cord potentials (SCP) was studied. The SSP components which show decrease in intensity and period depending upon a dose and time after irradiation were determined. The destruction of spinal input control systems was found. The causes and possible pathways of neuronal response depression which is probably due to synaptic structure damage have been considered. It is assumed that spinal potentials can be used as additive index of the extent of reaction to irradiation. PMID- 8193721 TI - [The effect of low-intensity prolonged impulse electromagnetic irradiation in the UHF range on the testes and the appendages of the testis in rats]. AB - The influence of the long (4 months, 2 hr/day) impulsive electromagnetic irradiation with the power density of 0.25 mW/cm2 on the testes and epididymides was studied. The results demonstrate the high sensitivity of the rat testes and epididymides to electromagnetic field of 3 GHz. Some destructive changes both in the seminiferous tubules and testicular tissue were found. The full recovery has not been observed even 4 months after irradiation was finished. PMID- 8193722 TI - [The behavioral reactions of rats in the early period following uniform whole body gamma irradiation at an absolutely lethal dose]. AB - Rats were irradiated with gamma rays (30 Gy) and spontaneous behavioral activity in an "open field" as well as formation of conditioned reflex of adversive behavior were registered in 1, 7-8 and 24 hr after exposure. The statistically verified depression of behavioral activity was found 24 hr after irradiation, while the prolongation of the latent period of conditioned reflex occurred as early as 1 hr after irradiation. The results obtained are discussed from the point of view of GABA system involvement in the changes observed. PMID- 8193723 TI - [The use of the multivariate estimation method for the objective evaluation of the effect of antihypoxic therapy in the first 24 hours after an absolutely lethal radiation injury]. AB - Three groups of rats (intact, irradiated with 30 Gy of gamma rays and treated after irradiation with the use of pharmacological and metabolic drugs protecting brain against hypoxia were studied. In 24 hours after the influence the animals have undergone the neurobehavioral testing and then were sacrificed, a number of neurochemical parameters depicting energy metabolism and metabolic GABA bypath in brain were studied (general number of parameters were 24). Using classical method of t-statistics only enhancement of labelled GABA catabolism and deterioration of general behavioral activity were verified, the modifying effect of the pharmacological and metabolic protection against hypoxia was not found. Using methods of multidimensional evaluation the protective and sanogenic character of the used method of therapy was verified. Thus, using discrimination analysis (Mahalanobis criterion) high similarity of intact and treated groups of animals was estimated. It was confirmed using methods of coupled and multiple correlation and method of route coefficients. The statistical connections between neurochemical and neurobehavioral parameters were found which can be useful for understanding of the mechanisms of the early postradiation syndrome development. PMID- 8193724 TI - [The effect of prolonged exposure to UV radiation on the state of the ocular media and on the parameters of the electroretinogram in the rabbit]. AB - Rabbits were exposed to vertically directed UV-B radiation (280-320 nm) 5 days a week during 10 months with daily dose 6.5 J/m2 (biological effective daily dose 0.83 J/m2). Within the first week expressed photokeratoconjunctivitis was observed, but to the end of third week state of cornea and conjunctiva became practically normal. Transparency of intra-eye structures was unchanged, functional activity of retina underwent undulatory alterations. Amplitude changes of a- and b-waves of electroretinogram reached 30% of control values during the first, were negligible within the second, and exceed control by 15-20% between 8 and 10-th months of exposure. Critical frequency of flashing was unchanged. PMID- 8193725 TI - [The effect of the amount of dialdehyde cellulose-bound enzyme on the activity of immobilized trypsin after gamma irradiation and in the storage process]. AB - It is found the complex effect of the bound enzyme concentration on the proteolytic activity of trypsin immobilized to dialdehydecellulose (preriodate oxidation) after gamma irradiation and in process of storage. It is shown the occurrence of three stages of immobilized enzyme inactivation in process of immobilization and storage. The velocity of inactivation did not depend on bound trypsin concentration. The ratio of proteolytic activity of samples before and after gamma irradiation was increased with the increase of immobilized to carrier enzyme concentration and was not change (in range of experiment error) in process of storage. The results were compared with that of crystalline trypsin. PMID- 8193726 TI - Expression of parathyroid hypertensive factor in hypertensive primary hyperparathyroid patients. AB - Hypertension is frequently associated with primary hyperparathyroidism, yet the mechanism of such hypertension is unknown. Parathyroid hypertensive factor (PHF) is a circulating hypertensive factor found in a proportion of human essential hypertensive patients as well as in spontaneously hypertensive rats (SHR). In the latter case, PHF has been shown to be secreted by the parathyroid gland. The purpose of this study was to determine if PHF expression might be responsible for the hypertension seen in primary hyperparathyroidism. Ten hypertensive and 10 normotensive primary hyperparathyroid patients underwent measurement of blood pressure and PHF pre- and post-parathyroidectomy. Cases reported are those of parathyroid adenomas. There were no significant differences between the hypertensive and normotensive groups preoperatively except that 9 out of 10 of the hypertensive group had significant PHF levels (mean 11 +/- 2 mm Hg vs 0.6 +/- 2 mm Hg, respectively, p = 0.003). Post-operative change in mean arterial pressure could be predicted by pre-operative PHF level, with all PHF-positive patients showing a fall in blood pressure (r = -0.73, p < 0.01). Post operatively, PHF was undetectable in PHF-positive patients. These results suggest that the parathyroid gland can express PHF in humans and that such expression may be responsible for a proportion of the high reported incidence of hypertension in primary hyperparathyroidism. PMID- 8193727 TI - Evaluation of self-measured home vs. clinic intra-arterial blood pressure. AB - Home blood pressure (BP) monitoring is useful in the clinical management of patients with hypertension and the identification of those with "white-coat" hypertension; i.e. high readings in the clinic but normal BP at home. In the process of evaluating this technique, we compared self-measured home BP with intra-arterial BP. Healthy white men (n = 40) of 20-40 years of age and body weight below 95 kg were recruited by advertising in the local newspaper. Following a standardized procedure, performed within 2-4 weeks of a response to the advertisement, BP was measured by a physician at a clinic screening, by the subject at home (14 readings in 7 days) and finally in the clinic concomitantly intra-arterially and oscillometrically. The correlation coefficient for mean (M) home BP (r = 0.73) and oscillometric BP (r = 0.74) against intra-arterial BP were slightly higher than for screening BP (r = 0.65). However, in plots of the differences for individual MBP between the methods against the average of the methods, it appears that at levels of average MBP above 100 mmHg, screening BP overestimates the BP level, while this was not the case for home BP or oscillometric BP. Thus, by using intra-arterial measurement as standard of comparison, subject self-measured home BP is a reliable method of estimating blood pressure level in young men. Home BP measured shortly after screening and recruitment provides useful information of resting BP in subjects who potentially may have initial anxiety about BP measurement. PMID- 8193728 TI - Circadian blood pressure variations in endocrine disorders. AB - Circadian rhythm of blood pressure and of heart rate was studied in patients with hyperthyroidism (n = 10), pheochromocytoma (n = 8), primary hyperaldosteronism (n = 7), and in a control group of essential hypertensive patients (n = 18) and of normotensive healthy subjects (n = 11). 24-hour blood pressure was monitored non invasively using SpaceLabs (SL 90207) with 8-min intervals in the daytime (8 a.m. to 10 p.m.) and 30-min intervals during night-time (10 p.m. to 8 a.m.). To characterize circadian blood pressure rhythm the difference between the mean blood pressure during daytime and that during night-time was calculated. In patients with hyperthyroidism the day-night difference of the systolic and diastolic blood pressure and of the heart rate was significantly reduced when compared to the normotensive control group (p < 0.05). The day-night difference of the systolic and diastolic blood pressure was significantly lower in the group with pheochromocytoma and hyperthyroidism than in the essential hypertensive controls (p < 0.05); the day-night difference of the heart rate was similar. In the patients with primary hyperaldosteronism the day-night differences of the systolic and diastolic blood pressure and of the heart rate was similar to those in essential hypertensive controls. We conclude that endocrine disorders affecting sympathetic activity like pheochromocytoma or hyperthyroidism influence the circadian blood pressure rhythm, whereas the renin-aldosterone-system has no major impact on the diurnal blood pressure variation. The results therefore support the hypothesis that circadian blood pressure variation is mainly mediated by a modulation of the sympathetic tone. PMID- 8193729 TI - Hypertension, primary hyperparathyroidism and the parathyroid hypertensive factor. PMID- 8193730 TI - Proximal renal tubular pressure-natriuresis-relation in essential hypertensives following acute vasodilatation. AB - Blood pressure (BP) and excretory function including lithium clearance were investigated during water-loading and constant infusion of 131I-hippuran and 125I iothalamate for measurement of renal haemodynamics in 8 untreated essential hypertensives (mean BP +/- SD: 169 +/- 14/107 +/- 6 mmHg) before and after vasodilatation with an i.v. bolus of the potassium-channel opener, pinacidil, 0.01 mg/kg. Systolic BP (-7 +/- 4%; p < 0.05) and diastolic BP (-13 +/- 8%; p < 0.01) decreased significantly and heart rate increased (11 +/- 8%; p < 0.01). Clearance (C) of lithium, sodium, urinary flow rate, potassium and absolute distal reabsorption of sodium all fell significantly. The changes of these variables were significantly correlated with the fall in BP (CLi:r = 0.92, CNa: r = 0.85, V: r = 0.81, CK:r = 0.84), despite no significant changes in renal haemodynamic parameters: glomerular filtration rate, renal plasma flow and renal vascular resistance. A proximal tubular effect was also indicated by a fall in Curic acid and fractional Curic acid. In conclusion, vasodilatation in essential hypertensives following administration of the potassium channel opener, pinacidil, induces a fall in blood pressure with a corresponding fall in fractional proximal tubular excretion of sodium and output of sodium and water from proximal to distal tubular segments, proposing an acute proximal tubular pressure-natriuresis relation. PMID- 8193731 TI - Therapy-resistant hypertension associated with central obesity, insulin resistance, and large muscle fibre area. AB - Obesity and an enhanced insulin response to oral glucose tolerance test are associated with therapy resistance in hypertension. In order to explore this association further we studied the insulin sensitivity of subjects with essential hypertension resistant to triple drug therapy (RH), with the euglycemic insulin clamp technique. Well controlled hypertensives, matched for age, gender and body mass index (BMI) served as controls. Male subjects (7 RH and 7 controls) were further investigated by biopsies of Musculus Vastus lateralis since structural conditions in skeletal muscles might have a role in the above association. Irrespective of pre-study drug therapy, therapy-resistant hypertensives had a lower insulin sensitivity index than controls (p < 0.05). In spite of the BMI match waist/hip ratio (WHR) in the RH males tended to be higher (p < 0.07). Insulin clearance tended to be lower in RH subjects (p = 0.09). BMI correlated with a reduced muscular capillary density (r = -0.77, p < 0.01). The average cross-sectional muscle fibre area was larger in RH subjects (p < 0.05). The mean muscle fibre area correlated with basal serum insulin (r = 0.63; p < 0.05). Rarefaction of the muscular capillary bed appears to be related to obesity. Larger muscle fibres might be an effect of the growth factor properties of insulin and could possibly correspond to hypertrophy of smooth muscle in the resistance vessels. This factor might contribute to the association of hyperinsulinemia and hypertension and attenuate the response to antihypertensive therapy. PMID- 8193732 TI - Comparison of felodipine and enalapril monotherapy in essential hypertension. AB - This study compared the efficacy and tolerability of monotherapy with felodipine and enalapril in patients with essential hypertension using a double-blind randomised crossover design. Thirty-five subjects (22 male, 13 female--ages: median 48 years, range 31-69 years) entered the randomised phases of the study and 32 subjects completed the study. Following a 4-week run-in placebo phase, the treatments were felodipine ("Plendil ER") 5-20 mg and enalapril 5-20 mg orally once daily for 8 weeks, each with matching placebos. Dose titration was at 2 and/or 4 weeks in each phase. Number of subjects with each different end-of-phase dose were for felodipine: 5 mg--8, 10 mg--11, 20 mg--13 and enalapril: 5 mg--6, 10 mg--9, 20 mg--17. Predose supine blood pressure (mean +/- SEM) was reduced in both active treatment phases compared with the run-in phase (159 + 2/101 +/- 1), but there was no significant difference in blood pressure between the active phases: felodipine 143 +/- 2/90 +/- 1 and enalapril 146 +/- 2/92 +/- 1. The most common adverse effects were for felodipine: headache, flushing, ankle swelling; and for enalapril: cough. Felodipine and enalapril as once daily monotherapy are thus of similar antihypertensive efficacy but with predictably different adverse effect profiles. PMID- 8193733 TI - Twenty-four hour profile of the anti-hypertensive action of isradipine in essential hypertension. AB - Isradipine, 2.5 mg twice daily and placebo were administered for 4 weeks to 11 untreated essential hypertensives in a double-blind, random order, crossover study. At the end of each phase patients were assessed by 36 h of continuous intra-arterial blood pressure monitoring, surface electrocardiography, and measurement of endogenous creatinine clearance, serum biochemistry and plasma renin activity. Arterial pressure was significantly reduced by isradipine, with mean reduction in systolic blood pressure of 11.0 mmHg and diastolic pressure of 13.2 mmHg over 24 h. There was no significant change in heart rate, endogenous creatinine clearance, serum biochemistry or plasma renin activity. PMID- 8193734 TI - Cardioreparation and the concept of modulating cardiovascular structure and function. AB - Hypertension and atherosclerotic cardiovascular disease represent major global health problems. Practising physicians are challenged daily by patients suffering adverse cardiovascular events, such as myocardial infarction, stroke, heart failure and sudden cardiac death. Major risk factors have been identified of which the most important is left ventricular hypertrophy. In recent years, growth factors, regulatory peptides and effector hormones of the renin-angiotensin aldosterone system have been identified as important modulators of cell growth and behaviour. It therefore follows that a major emphasis has been placed on the importance of abnormalities in organ structure as the primary basis for impaired function of the heart and vasculature, including large and medium sized arteries and resistance vessels, or arterioles. The concept of reparation recognizes the importance of abnormalities in tissue structure to the functional basis of disease. It suggests that the structurally remodelled heart and vasculature can be restored to, or toward, normal structure and function by suitable therapy. Experimental and clinical trials which address this premise are reviewed herein. PMID- 8193735 TI - The Hypertension Optimal Treatment Study (the HOT Study). AB - The Hypertension Optimal Treatment (HOT) Study is a prospective, randomized, multicenter study which will be conducted in some 20 countries world-wide. Two major issues will be investigated: i) What is the optimal target diastolic blood pressure during antihypertensive treatment with regard to the reduction in cardiovascular morbidity and mortality? In order to address this question patients will be randomized to three different therapeutic goals: a diastolic blood pressure < or = 90 mmHg, < or = 85 mmHg or < or = 80 mmHg; ii) The second aim is to evaluate the effect of a low dose acetylsalicylic acid (ASA, aspirin) 75 mg o.d. in comparison with placebo on cardiovascular morbidity and mortality. The first aim will be investigated in accordance with the PROBE design (Prospective Randomized Open Blinded Endpoint evaluation), whereas the evaluation of aspirin versus placebo will be conducted under double blind conditions. It is estimated that 1,100 clinical events will be needed in order to answer the question regarding the relationship between target diastolic blood pressure and major cardiovascular events. The collection of these events will require the enrollment of at least 18,000 hypertensive men and women aged 50-80 years to be followed for 2.5 years (about 40,000 patient years). All patients will be given felodipine 5 mg o.d. as basic antihypertensive treatment with the addition of a beta-blocker or an ACE-inhibitor in a second step, with further predetermined increments in dosage as required in order to obtain the randomized therapeutic goal. PMID- 8193736 TI - The effects of hypertension and diabetes mellitus on the vascular reactivity of resistance arteries. AB - We have studied the effects of both hypertension and streptozotocin-induced diabetes mellitus on alpha 1-adrenoceptor mediated vasoconstriction, endothelium dependent and endothelium-independent vasodilation. The experiments were performed in perfused mesenteric vascular bed preparations taken from age-matched SHR, WKY, diabetic SHR and diabetic WKY. For the alpha 1-adrenoceptor agonist methoxamine, the mesenteric preparations from SHR and diabetic SHR yielded significantly (p < 0.05) stronger maximal responses than preparations taken from WKY and diabetic WKY, respectively. The diabetic state significantly (p < 0.05) decreased the responsiveness to methoxamine in arteries from SHR and WKY. Hypertension does not significantly change the concentration response-curves for (acetyl-beta) methacholine, histamine, adenosine diphosphate and sodium nitroprusside. However, the sensitivity to endothelium-dependent vasodilation decreased in preparations from diabetic animals (< 0.05). It is concluded that mesenteric resistance arteries from SHR and diabetic SHR are more reactive to alpha 1-adrenoceptor stimulation, whereas diabetes reduces the responsiveness to methoxamine in WKY and SHR. Hypertension does not affect the endothelium dependent relaxation in mesenteric arteries. However, diabetes decreases the sensitivity to endothelium-dependent relaxation without altering the sensitivity to sodium-nitroprusside. These findings are indicative of a diabetes-induced endothelial dysfunction in mesenteric resistance arteries. In preparations from diabetic hypertensive rats the reduced response to methoxamine and the endothelial dysfunction seem to run parallel. PMID- 8193737 TI - Changes in autonomic tone following thrombolytic therapy for acute myocardial infarction: assessment by analysis of heart rate variability. AB - INTRODUCTION: Little data are available on changes in autonomic tone during the first 24 hours of acute infarction in patients undergoing thrombolytic therapy. Particularly, the association of changes in autonomic tone to reperfusion of the infarct-related artery has not been evaluated in man. Heart rate variability (HRV) is a noninvasive tool to assess cardiac autonomic tone, which carries prognostic information in postinfarction patients. METHODS AND RESULTS: To assess changes in autonomic tone with angiographically assessed success of thrombolysis in patients with acute infarction, the proportion of adjacent RR intervals different by greater than 50 msec (pNN50) was analyzed from 24-hour Holter monitoring initiated before the start of thrombolytic therapy in 103 consecutive patients. Mean heart rate (HR) and pNN50 were available in 95 of 103 patients and were separately analyzed for the first hour after initiation of thrombolysis (reperfusion phase) and the first 24 hours. As assessed by coronary angiography 90 minutes after start of thrombolysis, 74 patients (78%) had successful coronary artery reperfusion. HR averaged 72 +/- 13/min for the first hour in all 95 patients and 74 +/- 13/min for the first 24 hours. The respective values for pNN50 were 11.2% +/- 11.7% for the first hour and 9.7% +/- 9.2% for the first 24 hours. Patients with inferior myocardial infarction (MI) had a lower mean HR of 72 +/- 12/min versus 76 +/- 13/min (P = 0.11) and a higher pNN50 (11.2% +/- 9.8% versus 7.6% +/- 8.3%, P = 0.01) compared to patients with anterior MI. The mean HR correlated weakly with pNN50 (r = -0.33, P < 0.01). For patients with coronary artery patency after 90 minutes, mean HR was 70 +/- 12/min for the first hour compared to 80 +/- 13/min for patients without (P = 0.003). For the first 24 hours, these values were 72 +/- 12/min compared to 80 +/- 14/min (P = 0.02). For the first hour, pNN50 averaged 12.6% +/- 12.4% for patients with successful reperfusion compared to 6.6% +/- 7.3% for patients without (P = 0.024). For the first 24 hours, these values were 9.2% +/- 8.5% compared to 11.5% +/- 11.3% (P = NS). Patients with in-hospital ventricular fibrillation (n = 8) had a higher mean HR throughout the first 24 hours (88 +/- 16/min vs 73 +/- 12/min, P = 0.008) compared to patients with an uneventful course. Additionally, there was a trend toward a lower HRV in patients with ventricular fibrillation. CONCLUSION: Thrombolysis-induced reperfusion of the infarct-related artery results in a higher vagal tone during the early hours of MI as compared to failed reperfusion. This finding is independent from infarct location and associated with a trend toward a lower incidence of ventricular fibrillation during the acute phase of infarction. PMID- 8193738 TI - Ablation of left free-wall accessory pathways using radiofrequency energy at the atrial insertion site: transseptal versus transaortic approach. AB - INTRODUCTION: Transcatheter ablation of the left free-wall atrioventricular accessory pathways (AP) by delivery of radiofrequency current at the ventricular insertion site has been shown to be effective. The efficacy of such a technique targeting the atrial insertion site of the AP was evaluated. METHODS AND RESULTS: One hundred consecutive patients with left free-wall APs and symptomatic supraventricular tachyarrhythmias were included. APs were manifest in 55 patients and concealed in 45. There were 55 men and 45 women with a mean age of 35 years. A total of 107 left free-wall APs were identified in these patients. In these 100 patients, successful ablation was accomplished in all by using a transseptal (45 patients) or transaortic (54 patients) technique. In one patient, ablation was accomplished from within the coronary sinus. Seven patients required a repeat ablative procedure, which was performed successfully. During 107 ablative procedures, six were associated with nonfatal complications including pericardial effusion (hemopericardium) in two patients, mild mitral regurgitation in two patients, swelling of the left arm in one patient, and staphylococcal bacteremia in one patient. Eighty-two (82%) patients underwent a repeat electrophysiologic study 6 to 8 weeks after successful ablation and were found to have no functioning AP or inducible supraventricular tachycardia. During a mean follow-up of 20 +/- 8 months, none of the 100 patients had a recurrence of tachyarrhythmias. CONCLUSION: These data indicate that the atrial insertion site of the AP can be successfully ablated in the majority of patients with left free wall APs by using either a transseptal or transaortic approach. Furthermore, both techniques are associated with minimal morbidity and no mortality. PMID- 8193739 TI - Alpha 1-adrenergic receptor modulation of repolarization in canine Purkinje fibers. AB - INTRODUCTION: Alpha 1-adrenergic receptor stimulation increases contractility and prolongs repolarization. These effects are modulated by alpha 1-adrenergic receptor-mediated inhibition of transsarcolemmal potassium currents. METHODS AND RESULTS: We used standard microelectrode techniques to study the actions of 4 aminopyridine (4-AP), which blocks the transient outward current, I(to), and WAY 123,398, which blocks the delayed rectifier, Ik, on canine Purkinje fiber action potential prolongation induced by phenylephrine. At a basic cycle length of 1 second, phenylephrine (0.1 to 10 microM) dose-dependently prolonged action potential duration at 90% repolarization (APD90) from 331 +/- 10 msec to 400 +/- 12 msec (P < 0.05) at phenylephrine, 10 microM. Phenylephrine did not change phase 1 or plateau height. 4-AP (0.1 mM) decreased phase 1 magnitude, shifted plateau height to more positive potentials (from 0.1 +/- 1.8 mV to 14.3 +/- 1.1 mV [P < 0.05]), and shortened APD90 from 318 +/- 9 msec to 294 +/- 8 msec (P < 0.05). 4-AP did not block phenylephrine effects on APD90, which increased, at 10 microM phenylephrine, from 294 +/- 8 msec to 342 +/- 6 msec (P < 0.05). In contrast, WAY-123,398 (0.1 microM) prolonged APD90 from 360 +/- 6 msec to 452 +/- 6 msec (P < 0.05), and had no effect on plateau height. In the presence of WAY 123,398, phenylephrine no longer increased APD90. CONCLUSION: (1) Agents that block I(to) shorten APD in Purkinje fibers; and (2) the alpha-agonist mediated increase of APD in canine Purkinje fibers can be explained by inhibition of Ik. PMID- 8193740 TI - Bipolar stimulation of cardiac tissue using an anisotropic bidomain model. AB - INTRODUCTION: One of the fundamental electrophysiologic problems that has not yet been completely elucidated is the response of cardiac tissue to externally applied electric currents. A limited number of theoretical and experimental techniques has been used to study the electric behavior of cardiac tissue in the presence of stimulating currents, and to demonstrate that the anisotropy in the passive electrical properties of the tissue plays an important role in the genesis and propagation of the activation wavefront and the resulting potential distributions. METHODS AND RESULTS: In this work we have applied the finite element method to study the electric and magnetic fields produced by cardiac tissue in response to bipolar current injection, using a linear bidomain model to represent the tissue. We found that the transmembrane potential distribution close to the stimulus electrode has a rather complex geometrical pattern, with adjacent hyperpolarized and depolarized regions. CONCLUSION: This behavior is consistent with previous theoretical and experimental results and may have implications in the study of electrical stimulation of cardiac tissue that are not apparent using other models. PMID- 8193742 TI - Power spectral analysis of cardiovascular variability in patients at risk for sudden cardiac death. AB - The time series of successive heart periods present important variations around its mean value, determining the phenomenon of heart rate variability (HRV), assessed with both time and frequency domain approaches. A low standard deviation of the heart period (a time domain index of HRV) is a powerful prognostic indicator of sudden coronary death in patients recovering from acute myocardial infarction. Spectral analysis of HRV usually demonstrates two major components: indicated as LF (low frequency, approximately 0.1 Hz) and HF (high frequency, approximately 0.25 Hz). They are defined by center frequency and associated power, which is expressed in msec2 or normalized units. When assessed in normalized units, LF and HF provide quantitative indicators of neural control of the sinoatrial node. Numerous experimental and clinical studies have consistently indicated that the LF component is a marker of sympathetic modulation and HF a marker of vagal modulation; the LF/HF ratio is a synthetic index of sympathovagal balance. In the analysis of 24-hour Holter recordings of normal subjects, a circadian rhythmicity of spectral markers of sympathetic and vagal modulation is clearly present, with a sympathetic predominance during the day and a vagal predominance during the night. In patients recovering from an acute myocardial infarction, spectral analysis of HRV revealed an increased sympathetic and decreased vagal activity during early convalescence, and a return to their normal balance by 6 to 12 months. A clear increase of LF was also evident in patients studied within a few hours of the onset of symptoms related to an acute myocardial infarction, independent of its location. Similarly, LF increased during transient myocardial ischemia. An increase in markers of sympathetic activity has also been observed prior to episodes of malignant arrhythmias. Spectral analysis of HRV could help in the understanding of the role of abnormal neural mechanisms in sudden coronary death, thus contributing to its prevention. PMID- 8193741 TI - Radiofrequency catheter ablation of idiopathic left ventricular tachycardia: further evidence for microeentry as the underlying mechanism. AB - INTRODUCTION: Idiopathic left ventricular tachycardia with a QRS pattern of right bundle branch block and left-axis deviation constitutes a rare but electrophysiologically distinct arrhythmia entity. The underlying mechanism of this tachycardia, however, is still a matter of controversy. This report describes findings in a 42-year-old man who underwent successful radiofrequency catheter ablation of idiopathic left ventricular tachycardia. METHODS AND RESULTS: On electrophysiologic study, the tachycardia was reproducibly induced and terminated with double ventricular extrastimuli. Intravenous verapamil terminated the tachycardia whereas adenosine did not. Detailed left ventricular catheter mapping during sinus rhythm revealed a fragmented delayed potential at the mid-apical region of the inferior site near the posterior fascicle of the left bundle branch. At the same site, continuous electrical activity throughout the entire cardiac cycle was recorded during ventricular tachycardia. Repeated spontaneous termination of this continuous electrical activity in late diastole was followed immediately by termination of the tachycardia. Single application of radiofrequency current for 20 seconds at this site completely abolished inducibility of the tachycardia. After catheter ablation, at the identical site of preablation recording of the fractionated potential during sinus rhythm, no fragmented delayed activity could be recorded. There was no complication from the ablation procedure. CONCLUSION: The preablation recordings of fragmented delayed potentials during sinus rhythm and continuous diastolic electrical activity during tachycardia, together with ablation characteristics and previously reported electrophysiologic properties of this arrhythmia, may further support microreentry as the underlying mechanism in idiopathic left ventricular tachycardia. PMID- 8193743 TI - Monophasic action potentials: concepts to practical applications. AB - Monophasic action potential (MAP) recordings reproduce the repolarization time course of intracellular action potentials with high accuracy and provide precise information on the local activation time. With the advantage of in vivo application and the development of the safer and simpler contact catheter technique, MAP recording has become the method of choice for evaluating myocardial repolarization changes. This review aims to provide information on practical application of MAP recording in the clinical setting. MAPs can easily be recorded from the endocardium with the contact catheter technique in the electrophysiology laboratory and from the epicardium with electrode probes during open heart surgery. The technical aspects are described in detail. The rate dependence of myocardial excitability and repolarization and the effect of antiarrhythmic drugs on MAP duration and effective refractory period are thoroughly reviewed. The use of MAPs in detecting myocardial ischemia, in studying early afterdepolarization and triggered arrhythmias, in measuring dispersion of repolarization, in identifying intracardiac conduction and the development of the T wave, and in verifying the arrhythmogenic effect of mechanoelectric feedback are presented. Computerized automatic analysis of MAPs and the limitations of the MAP technique are also discussed. PMID- 8193744 TI - Anatomy of the AV node. PMID- 8193745 TI - Flushing with autologous blood improves intraoperative hemodynamic stability and early graft function in clinical hepatic transplantation. AB - Hemodynamic instability and hyperkalemia are common after reperfusion and may cause ischemic damage on the hepatic allograft. Two techniques for flushing hepatic grafts before reperfusion were studied to evaluate their effects on intraoperative hemodynamic and metabolic status and on early graft function in 83 consecutive adult hepatic transplantations. In the first 41 patients (group 1), the hepatic grafts were rinsed with 500 milliliters of lactated Ringer's solution (LR). In the subsequent 42 patients (group 2), in addition to LR rinse, the first 500 milliliters of portal blood to flush and reperfuse the liver were drained through the cannula inserted into the donor vena cava before unclamping the vena cava. After reperfusion, the mean arterial pressure decreased 30 +/- 4 percent in group 1 versus 17 +/- 2 percent in group 2 (p < 0.02), and serum K+ increased by 1.9 +/- 0.2 in group 1 versus 0.8 +/- 0.2 milliequivalents per liter in group 2 (p < 0.01). Hyperkalemic cardiac arrest was only seen in two patients in group 1. The K+ concentration in the first 100 milliliters of discarded blood was found to be 40 +/- 2 milliequivalents per liter. The 500 milliliters of discarded blood contained 8.3 +/- 0.4 milliequivalents, which was correlated with graft liver weight (p < 0.001). Early graft function, as measured by serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, total bilirubin and prothrombin time on postoperative day No. 2, was significantly better in group 2 than in group 1 (p < 0.05). The six-month graft and patient survival rates in group 1 were 66 and 75 percent, versus 90 and 95 percent in group 2 (p < 0.01 and p < 0.02, respectively). Further flushing with 500 milliliters of autologous portal blood resulted in smaller intraoperative shifts in serum K+, greater hemodynamic stability, better graft function and improved graft and patient survival. PMID- 8193746 TI - An improved method of needle localized biopsy of nonpalpable lesions of the breast. AB - We have created a modified technique of localization biopsy of the breast that more easily identifies the position of the wire tip after placement and before biopsy. After wire placement, metallic skin markers are placed on the nipple and wire entry site. The patient is then positioned on a roentgenography table in the same position to be used during biopsy. A supine roentgenogram of the breast is obtained. At the time of the biopsy, this roentgenogram is aligned with the corresponding markers on the skin of the patient and the position of the wire tip is noted. A curvilinear incision along Langer's lines can then be made at that site. This procedure was used in 53 consecutive biopsies of nonpalpable mammary lesions. In all instances, the biopsy incisions were independent of the wire insertion sites and in each instance, the lesion was excised in a single specimen. Compared with other techniques, our method is simple, inexpensive, requires no special equipment and results in only a minimal increase in radiation dose to the breast (50 millirad). The decrease in the amount of tissue dissection without decreasing accuracy afforded by our technique can improve compliance with the American Cancer Society's recommended surgical guidelines for breast preservation therapy. PMID- 8193747 TI - Natural history of entrapment of the popliteal artery. AB - Popliteal artery entrapment (PAE) is described with increasing frequency. Reviewing the world literature and corresponding with some investigators, we were able to collect 375 instances in 291 patients, including our personal experience (33 instances in 24 patients). The present study was done to establish the natural history and evolution of PAE. Two groups of patients were created to verify if an early diagnosis and treatment of PAE is justified. Group 1 included 129 patients treated by a simple musculotendinous section. In group 2, 226 patients were treated by a vascular procedure (bypass, thromboendarterectomy, other). Age, symptoms and arteriographic findings were the parameters considered in the two groups. Results demonstrated that patients in group 1 are younger than those in group 2 (p < 0.001). Preoperative symptoms demonstrated a larger number of mild symptoms (paresthesias, a cold foot and cramping after intensive physical training) in group 1, when compared with group 2 (p < 0.001). Arteriography demonstrated a larger number of patients with normal findings at rest, with popliteal stenosis or occlusion during maneuver, in group 1 than in group 2 (p < 0.001). PAE results in progressive arterial impairment. Early noninvasive screening is mandatory to detect PAE at an early stage. Surgical treatment is thereby limited to a musculotendinous section, which has the best results. PMID- 8193748 TI - Reverse phasic contractions are present in antiperistaltic jejunal limbs up to twenty-one years postoperatively. AB - One of the surgical procedures that has been performed to reduce symptoms of dumping is the antiperistaltic jejunal limb (APL). We hypothesized that the polarity of the Phase III activity fronts would be maintained after creation of an APL. To test that hypothesis, water perfused, low compliance intestinal manometry was performed upon four patients with APL, four patients with vagotomy, antrectomy and Roux-en-Y gastrojejunostomy (VARY) and four volunteers. The patients were studied for a minimum of four hours of fasting. Recordings were analyzed by visual inspection by two observers and results are expressed as mean plus or minus standard error of the mean. Statistical analysis was performed with Student's t test. Phase III activity fronts occurred more frequently (1.4 +/- 0.3 per hour) in the patients with a VARY reconstruction than in the volunteers (0.5 +/- 0.5 minute). The duration of Phase II activity was significantly less in the patients with the VARY reconstruction (19.1 +/- 5.1 minutes) than in the volunteers (49.5 +/- 5.2 minutes). Patients with reversed activity fronts showed statistically significant propagation velocity (3.0 +/- 0.6 versus 9.6 +/- 2.0 centimeters per minute) (p < 0.005), but longer Phase III activity fronts (8.0 +/ 0.8 versus 4.9 +/- 0.3 minutes) (p < 0.001) than in the volunteers. Although there were a number of abnormalities identified in the patients with VARY reconstruction, there were no reverse Phase III activity fronts seen in the four patients with APL reconstruction. The polarity of the small intestine is maintained up to 21 years after construction of an antiperistaltic jejunal segment. PMID- 8193749 TI - Limb recurrence-free interval and survival in patients with recurrent melanoma of the extremities treated with normothermic isolated perfusion. AB - To date, little is known about prognostic factors for limb recurrence-free interval and survival in patients with recurrent melanoma of the limbs treated with regional isolated perfusion. Therefore, 216 such patients treated with normothermic perfusion using melphalan during the period 1978 to 1990 were analyzed for patient and tumor related variables using a Cox proportional hazard model. The five year limb recurrence-free interval was 52 percent. For stage II (n = 67), IIIA (n = 71) and IIIAB and IIIB (n = 78) disease separately, these percentages were 53, 56 and 47 percent. In stage II disease, patients with a local recurrence adjacent to scar or skin graft had a significantly better five year limb recurrence-free interval than patients with satellites (75 versus 33 percent; p = 0.0009). Prognostic factors for limb recurrence-free interval were- in order of importance--tumor tissue left in situ, number of previous limb recurrences and total tumor surface area. The overall five year survival rate was 42 percent. For stages II, IIIA and IIIAB and IIIB disease, these percentages were 57, 45 and 25 percent, respectively. There was no survival benefit for patients with a local recurrence. Prognostic factors for survival were, in order of importance, stage of disease, gender, age, Breslow thickness, Clark level of infiltration of the primary melanoma and the number of lesions forming the indication for perfusion. The results of this study will eventually further delineate indications for perfusion. PMID- 8193750 TI - Modes of presentation and management of inflammatory aneurysms of the abdominal aorta. AB - The preoperative diagnosis of inflammatory aneurysms of the abdominal aorta (IAAA) is seldom made, yet knowledge of its presence would be an aid to the surgeon. A heightened awareness of the variety of clinical presentations of IAAA should prompt the clinician to consider this entity in the differential diagnosis of back pain, weight loss and obstructive uropathy. Hypovolemic shock, gastrointestinal bleeding and asymptomatic IAAA have also occurred, albeit much less frequently. Patients who are hemodynamically stable might benefit from a short period of diagnostic and therapeutic measures before operation. Patients undergoing aneurysm repair on an "urgent" rather than "emergent" basis have been shown to have lower mortality and morbidity rates with enhancement of their cardiopulmonary and renal status. Computed tomographic scanning preoperatively in stable patients using careful supervision can confirm the diagnosis and allow more time for patient and surgical team preparation. Knowledge and avoidance of technical pitfalls intraoperatively further lessens mortality and complications. PMID- 8193751 TI - Development of ovarian pathology after hysterectomy without oophorectomy. AB - This study was done to determine the occurrence of disease in retained ovaries after hysterectomy. A retrospective analysis of patient charts was performed, comparing the patient reports of women who had secondary ovarian lesions with those whose ovaries showed no pathologic findings during the ten year period of observation (1980 to 1990). The study included 1,265 women with at least one ovary saved after hysterectomy for benign indications. Main outcome measures were ovarian pathologic findings after hysterectomy requiring repeat operation. The overall incidence of lesions in retained ovaries was 3.95 percent. There was a 3 percent risk of having secondary ovarian pathologic findings within three years after hysterectomy, with a decreased risk for the following seven years (mean follow-up time of 60 months, range of three to 120 months). Histologic findings at reoperation included common benign conditions of the ovary. No instance of carcinoma of the ovary was found. The risk of having pathology in the retained ovaries after hysterectomy was significantly higher in women who had only one ovary saved, compared with those who had both ovaries saved (7.63 versus 3.47 percent; p < 0.05). The mean age at hysterectomy was significantly lower in women who had ovarian disorders subsequent to hysterectomy than in those who did not (39.3 versus 43.9 years; p < 0.001). In the group of women with secondary ovarian lesions, mean parity was significantly lower than in those without reoperation (1.22 versus 1.94; p < 0.0001). Women with unilateral oophorectomy at the time of hysterectomy had twice the risk of secondary ovarian lesions, compared with those without oophorectomy at hysterectomy. Determinants, such as age, parity and gravidity must be considered when deciding whether or not to perform oophorectomy at hysterectomy. PMID- 8193752 TI - A biomechanical study of the aponeurotic inguinal hernia repair. AB - The aponeurotic inguinal hernia repair is essentially a union of the aponeuroses of the external oblique and transversus abdominis muscles in the groin. Its tension-free status and resistance to intra-abdominal stress were measured in a biomechanical study. Comparative studies were made with the American Bassini procedure. Suture tensions were measured at three sites in six aponeurotic repairs and the mean tension was 3.9 +/- 2.9 grams, which was within the accuracy of the combined transducer and recorder measurement. Similar measurements in six American Bassini operations registered 633 +/- 230 grams mean tension. A relaxing incision in the Bassini repair reduced but did not eliminate tension. Mean tension figures remained at 401 +/- 198 grams. Specimens of external oblique aponeuroses in six random patients were tested, counter to their parallel fibers, in a tensiometer. The thickness of the specimens varied from 0.21 to 1.2 millimeters. The tissue mean stress capacity under tension was 4.1 +/- 1.9 x 10(6) pascals with a range of 2.5 to 6.5 x 10(6) pascals. An analysis was made of the impact of intra-abdominal pressure at five possible sites of failure in the aponeurotic repair. Established values of suture bite tissue tear resistance and our values of external oblique aponeurosis stress tension were used to calculate the resistance of the aponeurotic repair to established values of intra-abdominal pressure. The maximum reported intra-abdominal pressure is 26.6 kilopascals. In this series, the largest reconstructed inguinal floor was 5 square centimeters and supported a load of 1,360 grams force. There was a safety margin of 2.4 against a failure of tissue of minimal thickness (0.2 millimeter) in the aponeurotic repairs when subjected to maximum intra-abdominal pressure. With average thickness of specimen (0.45 millimeter) there was a safety margin of 5.4. The 2-0 polypropylene suture had a requirement of 1,590 grams force maximum knot pull strength, which was much greater than our measured tensions. The added suture-line tension created by the assumed intra-abdominal pressure with sutures spaced one-half centimeter apart was calculated to be 65 grams force. This figure is well below the reported tensions of 5,300 and 9,100 grams force resisting tissue pull through failure in the external oblique and transversus aponeurosis, respectively. The transversalis aponeurosis component of the repair had shown in the proceeding study a tensile strength greater than the external oblique aponeurosis, and by analogy, a competence to resist intra-abdominal pressure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8193753 TI - A critical appraisal of pathogenesis and morbidity of surgical treatment of chronic anal fissure. AB - Preoperative and postoperative manometric findings and the results of lateral internal sphincterotomy were analyzed in 44 consecutive patients affected with chronic anal fissure. Preoperatively, resting anal pressure was increased in 32 patients. At one month postoperatively, 23 patients showed normal pressures, whereas 14 were still hypertonic and seven, hypotonic. Only three patients still had a weak sphincter six months postoperatively. The overall morbidity rate was 31.8 percent. Minor complications occurred in 11 patients. Major complications affected three patients. Overall, impaired continence was recorded in eight patients, although only two complained of persistent, albeit lesser, defects of continence not requiring the use of pads. Nonoperative treatment should be reserved for few selected patients with recent, acute fissures. As for chronic and fissures, compared with other operative or nonoperative modalities of treatment, lateral internal sphincterotomy is a highly successful procedure and its minimal morbidity is well accepted by the patient. PMID- 8193754 TI - Indirect laryngoscopic evaluation of vocal cord function in patients undergoing transhiatal esophagectomy. AB - Vocal cord function was assessed by indirect laryngoscopy before and after transhiatal esophagectomy for carcinoma of the middle and lower esophagus. Unilateral vocal cord palsy was found in 16 (34 percent) of 47 patients, but three of these patients were not hoarse and coughed normally. Four patients were hoarse postoperatively but had normal vocal cord function on indirect laryngoscopic examination. All vocal cord palsies but one were on the left side and the left side of the neck was used for esophageal mobilization with the only exception of the one patient who had a right cord palsy after a right-sided neck dissection. Patients with impaired vocal cord function did not have a significantly increased stay in the intensive therapy unit or in the hospital, nor was there an increase in pulmonary complications. Vocal cord palsy is a recognized complication of transhiatal esophagectomy, and although it remains unresolved whether or not the recurrent laryngeal nerve damage occurs at the level of the aortic arch or in the neck, the present evidence suggests the latter site. The clinical impression of postoperative vocal cord palsy is often incorrect. PMID- 8193755 TI - Fetoscopy-guided fetal endoscopy in a sheep model. AB - Video-endoscopic surgical treatment of the fetus may, in the future, become an alternative to open fetal operation. Six 95-day-old fetal lambs were examined through intrauterine endoscopy using amnioinfusion and specially designed balloon tipped cannulas. The fetuses were monitored endoscopically for oxygen saturation, heart rate and temperature throughout the procedure. With a rigid 5 millimeter telescope and a flexible 3 millimeter endoscope, the respiratory and upper gastrointestinal tracts could be examined. No mucosal or other trauma was noted upon completion of the endoscopy; all lambs survived the procedure. While the applications of fetal endosurgery are likely to be similar to those of open fetal operation, fetal endoscopy (looking in the fetus) is a new entity for which clinical relevance (rather than mere feasibility) remains to be demonstrated. This technique, however, could become a valuable research tool to study fetal gastrointestinal and pulmonary physiologic factors in situ. PMID- 8193756 TI - Reherniation after repair of the abdominal wall with expanded polytetrafluoroethylene. AB - Defects of the abdominal wall that are not amendable to primary closure have to be bridged by synthetic materials. The use of a nonabsorbable expanded polytetrafluoroethylene (ePTFE) soft-tissue patch is advocated for this purpose. To investigate the suitability of the ePTFE patch, abdominal wall defects in 30 rats were repaired with ePTFE and compared with polypropylene (PP) mesh. Herniations and adhesions were scored, qualitatively and quantitatively, eight weeks after implantation and the patches were histologically examined. Herniations, all observed at the fascia and patch interface, were significantly more frequent in abdominal wall defects repaired with ePTFE (60 percent) than with PP (zero percent) (p < 0.001, chi-square test). Adhesion formation was less frequently found in rats treated with ePTFE and adhesions were less strongly attached. Histologic examination revealed no ingrowth of fibro-collagenous tissue into the ePTFE patch, whereas the PP mesh was completely incorporated into fibrocollagenous tissue, which was continuous with the adjacent fascia. We conclude that this study confirms our clinical experience that reherniations at the fascia and patch interface in abdominal wall defects closed with an ePTFE soft-tissue patch are the result of insufficient ingrowth of fibrocollagenous tissue into the patch, which results in an insufficient anchorage of the patch to the fascia. PMID- 8193757 TI - The gynecologic contribution to intestinal obstruction in females. AB - This study was done to identify the cause of intestinal obstruction with particular emphasis on the gynecologic and perioperative related causes. All medical records from females with the discharge diagnosis "intestinal obstruction" from 1988 to 1991 at Columbia Presbyterian Medical Center were requested. The patient series consisted of the first 100 completed charts received. Forty-eight percent of those patients with intestinal obstruction had experienced a previous gynecologic or obstetric event that could account for the obstruction. Primarily, the gynecologist managed more than 20 percent of all female patients with intestinal obstruction. The most common causative factors contributing to intestinal obstruction were postoperative adhesions (59 percent) and tumor (17 percent). Fifty-six percent of the patients with intestinal obstruction associated with postoperative adhesions had a history of previous gynecologic and obstetric operation. Hysterectomy was the most common previously performed operation. In this series, cesarean section was less likely and myomectomy was more likely to cause subsequent intestinal obstruction than expected. Of 59 female patients with postoperative adhesions associated with intestinal obstruction, 31 had the original operative reports available for analysis. Eleven of these patients were taken to the operating room for management of the obstruction. In the nine patients who had surgical peritoneal closure in the original operation, the adhesions causing the obstruction were always to the site of reperitonealization. In the two patients in whom the peritoneum was left open, the adhesions causing obstruction were remote from the site of spontaneous reperitonealization. In an unselected patient series of intestinal obstruction, a history of previous gynecologic pathology is a significant factor contributing to the total number of instances of intestinal obstruction in females. Also, surgical peritoneal closure may result in an increase in the incidence of intestinal obstruction. PMID- 8193758 TI - Harvesting of the liver without in situ cannulation of the portal system. PMID- 8193759 TI - Technical aspects of minicholecystectomy. PMID- 8193760 TI - A simple one-handed method to secure drains and tubes. AB - A technically elegant, fast and reliable method to secure drains and tubes is presented herein. The method can be used with any type of drains and with any suture material. PMID- 8193761 TI - A new technique for left renal cryopreservation. AB - Our technique for left renal cryopreservation seems to have promise for preventing renal failure after thoracoabdominal aortic aneurysm repair. Based on the evidence we have obtained with this limited study, we plan to continue using this technique with selected, high-risk patients. PMID- 8193762 TI - A secured technique of sleeve anastomosis of hepatic arterial reconstruction in transplantation of the liver in pigs. PMID- 8193763 TI - Hysteroscopic resection of uterus septus versus abdominal metroplasty. AB - The new hysteroscopic approach toward pregnancy loss associated with uterine septum offers several advantages over abdominal metroplasty. However, several safeguards should be taken: laparoscopic or sonographic guidance should accompany hysteroscopic metroplasty; postoperative HSG or hysteroscopy is recommended; there is no advantage of IUD insertion postoperatively; sequential estrogen progesterone therapy postoperatively is optional, but of no proved benefit; a hysteroscopic approach toward uterine septum is the preferred procedure, even when laparotomy for treatment of pelvic endometriosis or intrapelvic adhesions is indicated, and, although its value is not established, a short perioperative cause of prophylactic antibiotics seems to be warranted. PMID- 8193764 TI - Endothelial cell monolayers viewed by TIRF microscopy. PMID- 8193766 TI - Flow cytometric DNA content analysis of thymidine-induced cell death. PMID- 8193765 TI - Growth of MDCK cells on non-transparent supports. PMID- 8193767 TI - Exposure of cultured beating rat heart cells to electromagnetic fields. PMID- 8193768 TI - Morphology of Drosophila S-2 cells in different culture conditions. PMID- 8193769 TI - Evaluation of two methods for elimination of mycoplasma. PMID- 8193770 TI - Primary cultures of rat hepatocytes in hollow fiber chambers. AB - Hepatocyte culture may represent an alternative to the use of animals to study drug detoxification by the liver. An ideal in vitro system should closely mimic the in vivo environment by providing continuous media perfusion and oxygenation, and should facilitate sampling of cells and culture media. To meet these criteria, a hollow fiber bioreactor seeded with isolated rat hepatocytes was developed and tested by measuring the formation of three products of the oxidative metabolism of diazepam and the glucuronidation of phenolsulfonphthalein (PSP). To compare the performance of conventional monolayer culture to that of the bioreactor system, diazepam metabolism was studied for 45 days in both systems. The oxygen dependency of diazepam metabolism was evaluated by perfusing the bioreactor in an oxygen-rich atmosphere (30%). Total diazepam metabolism was twofold higher in the O2-rich perfused hollow fiber cultures than in the cultures perfused under normal conditions, reflecting an increase in temazepam and oxazepam production. Diazepam detoxification activity was significantly enhanced by oxygen (P < or = 0.001) over the life of the perfused cultures. PSP metabolism was similar in all three culture systems. By Day 10, diazepam metabolism in the oxygenated bioreactor system was 44% of the in vivo activity of rat hepatocytes. This activity dropped to 30% by Day 25 of culture. These results justify the use of perfused culture systems for in vitro detoxification studies as an alternative to animal use and emphasize the capacity of a culture device perfused under O2 enriched conditions to maintain long-term P450 activity of rat hepatocytes. PMID- 8193771 TI - Decreasing glycolysis increases sensitivity to mitochondrial inhibition in primary cultures of renal proximal tubule cells. AB - We have previously shown that shaking the culture plates (SHAKE) of rabbit renal proximal tubule cells (RPTC) to maintain adequate aeration increased aerobic metabolism and decreased the induction of glycolysis compared to RPTC cultured under standard conditions (STILL). However, glycolysis in SHAKE RPTC remained elevated compared to glycolysis in proximal tubules in vivo. In the present study the contribution of culture medium sugar composition and concentration to glycolytic metabolism was assessed in RPTC. SHAKE and STILL RPTC cultured in 5 mM glucose contained lactate levels equivalent to the respective SHAKE and STILL RPTC cultured in standard culture medium which contains 17.5 mM glucose. Similarly, the activity of lactate dehydrogenase was unchanged by lowering the medium glucose concentration. Substituting 5 mM galactose for 5 mM glucose in the culture medium significantly reduced the lactate content of both SHAKE and STILL RPTC but had no effect on lactate dehydrogenase activity. Cell growth was equivalent under all culture conditions. Sensitivity to mitochondrial inhibition was determined for each culture condition by measuring cell death after exposure to the respiratory inhibitor antimycin A. The results showed a hierarchy of sensitivity to antimycin A (5 mM galactose SHAKE > 5 mM glucose SHAKE > 17.5 mM glucose SHAKE = 17.5 mM glucose STILL), which was generally inversely correlated with the level of glycolysis as measured by lactate content (17.5 mM glucose STILL > 17.5 mM glucose SHAKE = 5 mM glucose SHAKE > 5 mM galactose SHAKE). PMID- 8193772 TI - Human chorionic gonadotropin inhibits proliferation and induces expression of inhibin in human breast epithelial cells in vitro. PMID- 8193773 TI - Primary culture of gill epithelial cells from the sea bass Dicentrarchus labrax. AB - We have developed the first explant technique that allows the in vitro study of gill physiology and biochemistry in marine species. Gill fragments were cultured at 17 degrees C, in atmospheric PCO2, with nutrient medium (Leibovitz L15), pH 7.8, supplemented with 10% fetal bovine serum and adjusted to the osmolarity of fish plasma (350 mOsm/liter). Coating plates with collagen, gelatin, or polylysin did not improve our results. Decrease in osmotic pressure, removal of bovine serum, or its replacement by fish serum inhibited growth from the explants. Approximately 50% of the explants produced cell growth, and after 4 days of culture a monolayer of contiguous cells was formed. This technique is rapid and does not require the use of enzymes. The cells appeared flat and thin with an epitheloid shape. They looked polygonal with a maximum length of 10 to 50 microm. Evidence that they are unique gill cells is the presence of polymorphic surface crenelations (microplicae), prominent Golgi apparatus, tight junctions and desmosomes. Comparison with in vivo tissue showed them to be epithelial cells having differentiated in a homogeneous population of respiratory-like (pavement) cells. They are polarized with their apical surface facing the culture medium. The development of this culture system represents a new tool for cellular approaches to determine precisely the functions and transport mechanism of gill cells. PMID- 8193774 TI - In vitro DNA synthesis as indicator of mammary epithelial cell division: [14C]thymidine uptake versus flow cytometry cell cycle analysis. AB - Mammary and adipose explants from eight mid-lactation Holstein cows were co cultured for 24 h in the presence or absence of liver explants, 1 microgram/ml pituitary bovine somatotrophin, or 100 ng/ml insulinlike growth factor-I. Liver explants in the media significantly depressed DNA and protein synthesis by mammary tissue as measured by [14C]-thymidine and amino acid incorporation. As measured by flow cytometry, the concentration of DNA in the G0G1 and G2M cells and the percentage of cells in the G0G1 population of mammary tissue was also significantly depressed by liver tissue. Changes in the percentage of cells in the S and G2M phases were not significant. Insulinlike growth factor-I in the presence of liver explants depressed protein synthesis, thymidine incorporation, and the concentration of DNA in the G0G1 and G2M cells compared to control but did not affect the percentage of cells in the G0G1, S, or G2M phases. Previously it was assumed that changes in [14C]thymidine incorporation indicated that changes in cell division were occurring. Flow cytometry revealed that changes in DNA content of mammary cells as a result of liver or hormonal stimulation were not due to changes in cell division. Indications are that differences in cellular DNA content result from changes in the rate of amplification of individual genes responsible for milk protein synthesis. PMID- 8193775 TI - Ouabain is a reversible inhibitor of myogenic fusion. PMID- 8193776 TI - The nurse and the HIV patient--what should the healthcare policy be? PMID- 8193777 TI - The healing relationship. PMID- 8193778 TI - Revolution looks at clinical practice: burnout or exploitation. PMID- 8193779 TI - Strike! PMID- 8193780 TI - "No justification" for St. Joe's strike--another voice. Interview by Eleanor Taub. PMID- 8193781 TI - Wake up nurse educators! Get with the empowerment program! PMID- 8193782 TI - The quiet revolution in nursing management. Interview by Carolyn S Zagury. PMID- 8193783 TI - 10 great things about chemotherapy. PMID- 8193784 TI - Financial advisement. Interview by Lizabeth J. Augustine. PMID- 8193785 TI - Nursing's noblesse oblige. PMID- 8193786 TI - Michele Sobczak--"my tragedy made me a fighter!". Interview by Linda Saslow. PMID- 8193787 TI - After the shift, a reunion with rage, grief, anger, sadness. PMID- 8193788 TI - Caring! Nursing's undervalued strength. PMID- 8193789 TI - The U.S.S. hope. PMID- 8193790 TI - Radical reflection on tears. PMID- 8193791 TI - Making a case for nursing: earning a seat at the policy table. PMID- 8193792 TI - Ten ways nurses can change their lives with laffter and play. PMID- 8193793 TI - Sexual harassment in the hospital. PMID- 8193794 TI - Spiritual retreats. PMID- 8193795 TI - The state license hearing--information for empowerment. PMID- 8193796 TI - "Nurse-consultant" could this be your next career title? PMID- 8193797 TI - Total quality management--can it work for nurses? PMID- 8193798 TI - Empowerment-based practice. PMID- 8193799 TI - A voice of one's own: risk-taking in nursing education. PMID- 8193800 TI - Bouquets. PMID- 8193801 TI - [Studying and working in 2 countries]. PMID- 8193802 TI - [Inquiry among Bavarian nursing schools]. PMID- 8193803 TI - [Nursing process during training]. PMID- 8193804 TI - [Learning to teach. Students guiding students]. PMID- 8193805 TI - [Safe work methods using a functional hygiene plan]. PMID- 8193807 TI - [You and I are part of the environment too]. PMID- 8193808 TI - [Rehabilitating and rehabilitated care]. PMID- 8193806 TI - [Practical hygiene measures]. PMID- 8193809 TI - [Tendencies toward privatization in the field of health care delivery. A challenge for nursing management]. PMID- 8193810 TI - [Effects of changes in the legal form on nursing]. PMID- 8193811 TI - [Employee's rights. Change of a community hospital into a limited liability company]. PMID- 8193812 TI - [We demand quality, how about you?]. PMID- 8193813 TI - [Quality in ambulatory care]. PMID- 8193814 TI - [Mentoring as a sign of quality in continued education]. PMID- 8193815 TI - [To suppress or to master?]. PMID- 8193817 TI - [Project organization and management in the hospital]. PMID- 8193816 TI - [Between duty and love. Thoughts on Peter Strasser's "The limits of love ethics"]. PMID- 8193818 TI - [Aging--a social catastrophe?]. PMID- 8193819 TI - [Beginnings in geriatric rehabilitation. The restoration of physical and mental functions is hardly possible without teamwork]. PMID- 8193820 TI - [Aging and old age in geriatric research]. PMID- 8193821 TI - [Care in rehabilitating geriatrics: beginnings, models, targets]. PMID- 8193822 TI - [Activating therapeutic geriatric care]. PMID- 8193823 TI - [Old age in nursing education]. PMID- 8193824 TI - [Care of the elderly--one ought to be able to study it]. PMID- 8193825 TI - [Dealing with the demented elderly]. PMID- 8193826 TI - [With the help of validation we can find the clearings in the fog of confusion]. PMID- 8193827 TI - [Disorders concerning learning and achievement in children and adolescents]. PMID- 8193828 TI - [Hydrocephalus in children]. PMID- 8193829 TI - [Alcoholism--disease of the whole family]. PMID- 8193830 TI - Lipid profiles. AB - Lipid profiles are only part of the cardiovascular status of the patient. Treatment should be directed at the cause and not the lipid profile numbers. The minority of patients with serious problems should be defined and treated and the others should be left alone. There is no single magic drug and dietary advice can work well if given by experienced, personable professionals. PMID- 8193831 TI - Cholestasis in infancy: 2. AB - Neonates with cholestasis present in several ways but all cases need to be investigated. Prompt diagnosis is imperative as age at treatment can be a major factor affecting the prognosis. The modes of presentation of infants with conjugated hyperbilirubinaemia are discussed and a plan for the investigation of such infants is suggested. PMID- 8193832 TI - Quest for continence: surgery for ulcerative colitis and familial adenomatous polyposis. AB - In the past decade pelvic pouch procedure (restorative proctocolectomy) has become the surgical treatment of choice for ulcerative colitis and most cases of familial adenomatous polyposis. It is an operation that eradicates disease yet restores gastrointestinal continuity and maintains continence. PMID- 8193833 TI - Refractory chronic fatigue syndrome in adolescence. PMID- 8193834 TI - A dangerous complication of central venous cannulation. PMID- 8193835 TI - Terminal care of gynaecological malignancy. AB - Gynaecologists in general are not trained to manage terminally ill patients. This article discusses the purpose of terminal care, some ethical difficulties in management, and who should be caring for these patients. It also reviews the clinical improvements that have developed over the past 10 years in other disciplines and their application to gynaecology. PMID- 8193836 TI - Recent advances in the development and use of plasma concentrates. AB - The consequences of blood donations infected with human immunodeficiency virus, the rapid advances in protein fractionation and the introduction of recombinant DNA technology have revolutionized the range of plasma products available to the clinician. This article reviews these developments and describes recent recommendations on their use. PMID- 8193837 TI - Talking to the lost tribes: SHO training in North-East Thames. PMID- 8193838 TI - Difficult patients. AB - All doctors have a cluster of patients they class as 'difficult'; patients whose name on an appointment list or whose face in the waiting room makes their heart sink or their blood pressure rise. The purpose of this article is to help the consultant to handle such patients more successfully. PMID- 8193839 TI - Cancer death. PMID- 8193840 TI - Human tissue research: is legislation needed? PMID- 8193841 TI - Human tissue research: is legislation needed? PMID- 8193842 TI - Human tissue research: is legislation needed? PMID- 8193843 TI - Needle cricothyrotomy. PMID- 8193844 TI - Sternal osteomyelitis. PMID- 8193845 TI - Is the type A/B typology alive and well? PMID- 8193846 TI - Management of acute pain. AB - This review discusses the inadequacies of postoperative pain management in the UK and recommendations to improve its quality. Advanced pain-relieving techniques are available; in this article we discuss the practical considerations of delivering these successfully to patients through the introduction of acute pain teams, and especially through extension of the nurses' role. PMID- 8193847 TI - Autonomic function following myocardial infarction. AB - There is evidence that impaired autonomic function is a significant risk factor for ventricular arrhythmias and sudden death following myocardial infarction. Measurement of heart rate variability and assessment of baroreflex sensitivity can identify patients at high risk from arrhythmic complications postinfarction and may become useful in risk stratification and management. PMID- 8193848 TI - Magnetic resonance imaging in joint disease. AB - Magnetic resonance imaging permits accurate and non-invasive assessment of the internal structure of joints. Consequently, it is reducing the requirement for both arthrography and diagnostic arthroscopy in the evaluation of patients with suspected internal derangement of joints. PMID- 8193849 TI - The value of the delay phenomenon in flap prefabrication: an experimental study in rabbits. AB - Neovascularisation of thin skin flaps after arteriovenous pedicle implantation (flap prefabrication) and the impact of the delay mechanism on the viability of these flaps were investigated. Twenty-four full thickness skin flaps were raised in twelve New Zealand white rabbits. Delay incisions were made at the lateral borders of the planned flaps at the same time as pedicle implantation, 1 week before pedicle implantation, or 1 week after pedicle implantation and the flaps based on the implanted vessels raised at 2 weeks after implantation. Flap survival assessed at 1 week was found to be improved when flap delay was performed 1 week before or after pedicle implantation. Angiographic studies demonstrated an increased density and linearity of the vascular pattern in these delay group flaps. The combination of the time-tested concept of delaying a flap with the newer technique of flap prefabrication appears to improve flap viability. PMID- 8193850 TI - The effect of allopurinol on experimental island skin flap survival under prolonged periods of arterial ischaemia. AB - The aim of this study was to assess the effect of allopurinol on rat groin flaps rendered ischaemic by selectively occluding the feeding femoral artery and reperfused by means of microsurgical anastomosis. For the establishment of the critical arterial ischaemia time, the femoral artery of 29 rat groin flaps isolated on the inferior epigastric pedicle was occluded for 10, 12 and 14 h. Following 12 h or more of ischaemia, 5.25% of the flaps survived, compared to 40% survival after 10 h (p = 0.04). In the second stage of the study, 34 rat groin flaps were subjected to arterial ischaemia for 12 h. Of these, 12 rats received allopurinol solution I.V. 30 min prior to reperfusion, 10 received the vehicle solution (control) and 12 underwent no treatment (control). After 7 days, survival of the groin flaps was observed in 41.7%, 0 and 8.3% of the groups, respectively (p = 0.0164). This study suggests that systemic administration of allopurinol has a beneficial effect on rat arterial ischaemic groin flaps and may prolong their critical ischaemia time. PMID- 8193851 TI - An evaluation of a new lactic acid polymer drug delivery system: a preliminary report. AB - A new drug delivery system, made of a mixture of DL-lactic acid polymer and a copoly (L-lactic acid/delta-valerolactone) polymer (LAP) containing varying concentrations of Ofloxacin, has been evaluated. Results revealed that a LAP drug delivery system containing 0.03% Ofloxacin inhibited the in vitro growth of clinically derived Staphylococcus aureus and Pseudomonas aeruginosa. Further, in an in vivo situation in rats, at 1 week after the wound was inflicted, no infection was macroscopically seen in split-thickness wounds that had been covered by LAP drug delivery system containing 0.5 or 0.03% Ofloxacin, and more than 80% of the wound area had epithelialised. PMID- 8193852 TI - Rationing and resource management. PMID- 8193853 TI - Breastfeeding after reduction mammaplasty. AB - A retrospective study was performed of 30 women who had undergone breast reduction and subsequently wished to breastfeed. Breastfeeding capabilities were assessed by a trained lactation consultant. Findings indicate that in women who have a physiological type of operation then breastfeeding is usually possible (18 patients out of 19), although complementary feeds may be required. We strongly suggest that all functioning breast tissue that remains after reduction mammaplasty be left attached to the nipple in a physiological manner to allow subsequent breastfeeding. PMID- 8193854 TI - Morbidity of otoplasty: a review of 562 consecutive cases. AB - Otoplasty is a routinely performed procedure in virtually all plastic surgery units. However, there are few comprehensive reports in the literature on the incidence of complications. In a review of 562 consecutive patients we found significant morbidity. Residual deformity, haemorrhage, infection, keloid/hypertrophic scarring and anterior skin necrosis were recorded and incidence determined. Cases requiring revision i.e., those with residual deformity were analysed further. The fault at the primary procedure was mostly that of design (73.4%), although many other residual problems were due to poor execution of technique (26.6%). Steps are described to minimise the need for such revision. PMID- 8193855 TI - The role of MRI scanning in the diagnosis of cervical lymphadenopathy. AB - In a blind, prospective trial, 42 patients undergoing 51 cervical lymph node dissections for head and neck malignancies were investigated by a preoperative MRI scan. Histological examination of the dissection specimens recorded the distribution, size, percentage of neoplastic involvement and any extra-capsular spread of the sampled nodes. The MRI correctly diagnosed all 17 positive nodes (sensitivity 100%). However it could not differentiate between enlarged reactive and malignant nodes, so there was a significant false positive rate (specificity 53%). Routine use of MRI scans will allow an unnecessary neck dissection to be avoided in a patient with a clinically negative neck who also has a negative MRI scan. PMID- 8193856 TI - Fronto-orbital re-operation in craniosynostosis. AB - The need for fronto-orbital re-advancement is reported from all cases of craniosynostosis operated on in the Birmingham and Oxford Craniofacial Units since 1979. Analysis of the 219 cases demonstrates a significantly higher re operation rate in cases of syndromal craniofacial dysostosis or unilateral coronal synostosis initially operated on below the age of 6 months. Mild bicoronal, sagittal and metopic synostotic cases, however, did uniformly well with the timing of initial surgery having little influence on the re-operation rates. PMID- 8193857 TI - A new approach to persistent traumatic peroneal nerve palsy. AB - Currently used tendon transfers for persistent traumatic paralysis of the common peroneal nerve are based on the transfer of the posterior tibial muscle, an antagonist muscle to the paralytic group of muscles. In order to achieve voluntary active dorsiflexion of the foot and automatic walking we have transposed the lateral head of the gastrocnemius to the anterior side of the lower leg, at the same time suturing the undamaged proximal end of the deep branch of the peroneal nerve to the motor branch of the tibial nerve innervating the lateral head of gastrocnemius muscle. After nerve regeneration and neurotisation the transposed lateral head of gastrocnemius was innervated by the deep branch of the peroneal nerve and thus it took over the function of the paralytic muscles. The indications for the operation, the surgical technique, and the results obtained in 6 cases are presented. PMID- 8193858 TI - Reconstruction of the quadriceps apparatus following open injuries to the knee joint using pedicled gastrocnemius musculotendinous unit as bridge graft. AB - The objectives of treating open knee joint injuries with disruption of the distal quadriceps mechanism are to ensure rapid wound healing and to restore joint function. For this it is necessary to provide soft tissue cover, control infection, restore full extension of the knee by reconstruction of the extensor apparatus and prevent joint stiffness by early mobilisation. Two cases are presented where the gastrocnemius (medial half) musculotendinous unit has been used to reconstruct, in one stage, the extensor apparatus and at the same time to provide soft tissue cover. PMID- 8193859 TI - Scalp tourniquet. AB - A pneumatic tourniquet with special features for the scalp region has been devised. A safe and well controlled surgical ablation can be performed with shortened operative time. The new tourniquet permits a larger access to the scalp and easier applicability to different cranial sizes. The tourniquet development, clinical indications, and illustrative cases are demonstrated. PMID- 8193860 TI - Reconstruction of the cervico-thoracic oesophagus with a tubed latissimus dorsi myocutaneous pedicled flap. PMID- 8193861 TI - Freeman-Sheldon syndrome: surgical correction of microstomia. AB - In this report, we describe a case of microstomia associated with club feet and ulnar deviation of the hands (Freeman-Sheldon syndrome) and the surgical technique for correction of the oral deformity. PMID- 8193862 TI - A method of improving the comfort of loupes. PMID- 8193863 TI - EMLA: an aid to suture removal following cleft lip repair. PMID- 8193864 TI - Debridement by brushes. PMID- 8193865 TI - New technology and the gastrointestinal endoscopist. A different perspective. AB - Developments in gastrointestinal endoscopy technology are occurring at an exponential rate. Driven by a better understanding of nature, better tools for imaging, measuring, sensing, modeling, and analyzing, as well as more sophisticated researchers and research techniques, developments that used to take decades occur in a fraction of the time. This is as true in medicine as it is in other areas of science; it is especially true in gastrointestinal endoscopy. PMID- 8193866 TI - Expandable endoprostheses for gastrointestinal stenoses. AB - Expandable endoprostheses have the theoretic advantage of placement into strictures that have previously been considered inaccessible because of acute angulation or anatomic constraint. Moreover, their placement through small diameter insertion catheters has the potential to minimize tissue trauma associated with rapid dilation and to improve placement accuracy. With few exceptions, data using these systems remain sparse, however. The stents are expensive and variably imbed into local tissue, and the prostheses and their delivery systems alike continue to undergo refinement. PMID- 8193867 TI - Laser-induced fluorescence spectroscopy. AB - Lasers have been a part of medicine and surgery since the late 1960s. In the past 5 years, however, there has been growing interest in using lasers as diagnostic devices, an area of research that has been termed optical diagnostics. Optical diagnostic techniques seek to provide diagnostic information about tissue by using light in a probing, yet nondestructive fashion. A large number of optical methods are available to endoscopists, but to date, only laser-induced fluorescence has been investigated in any detail. PMID- 8193868 TI - Tissue sensitizers. AB - A second generation of tissue sensitizers has been formulated for the photodynamic ablation of cancer. The photophysical and biologic properties of these agents will determine their activity and clinical use. Investigations of sensitizer properties are discussed, providing a foundation for sensitizer selection, followed by a summary of clinical reports. Tissue sensitizers may be particularly effective for the noninvasive ablation of early cancers. PMID- 8193869 TI - Endoscopic antireflux techniques. Endoluminal and laparoscopic. AB - Overall, endoscopic management of GER is an exciting new field of therapy or potential therapy. Endoluminal methods have developed slowly and remain experimental. Laparoscopic methods have developed rapidly and are being applied in clinical settings. The future looks bright and is open to the endoscopist's creativity. Continued scientific comparisons of techniques are needed to ultimately define optimal techniques and outcomes. PMID- 8193870 TI - Endoscopic measurement of pancreatic blood flow. AB - Based on the notion that reductions in pancreatic blood flow may play a role in the pathophysiology of chronic pancreatitis, a method for measuring pancreatic blood flow, using H2 gas clearance with a ductal electrode, was developed. Preliminary animal experiments using this methodology suggest that the fibrotic pancreas behaves like a closed compartment. The scarring results in ductal and interstitial hypertension, which decreases pancreatic blood flow. This reduction in blood flow may be important in both the pathogenesis of the disease as well as the etiology of the pain. Preliminary human studies, measuring pancreatic blood flow with an H2 electrode placed endoscopically, support these findings. Further studies will be necessary to confirm this novel hypothesis. PMID- 8193871 TI - High-intensity focused ultrasound. AB - High-intensity focused ultrasound (HIFU) is a technology that permits the use of ultrasound waves used for imaging and then focuses them as one would use a magnifying glass to focus sunlight. The ultrasound energy is absorbed by tissue and converted to heat and can be used to ablate tissue. This article summarizes the technology, mechanism of action, technique, and early clinical results of HIFU, then concludes with some potential future applications of this technology. PMID- 8193872 TI - Endoscopy for the year 2000. AB - With the rapid advancement in technology, there is a revolutionary paradigm shift in the delivery of health care: physicians are now interacting with their patients via an "electronic interface." This interface will make possible the future of endoscopy and endoscopic surgery by taking advantage of the emerging technologies in robotics, micro-robotics, telepresence, and virtual reality. PMID- 8193873 TI - ERCP training in the 1990s. Time for new ideas. AB - Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most demanding procedures performed by gastrointestinal endoscopists; however, surprisingly little is known about how the necessary hand-eye coordination and cognitive skills are acquired. Prospective studies are needed to confirm (or refute) retrospective data suggesting that ERCP training is protracted; many aspiring ERCP endoscopists complete their fellowships with inadequate diagnostic and therapeutic skills. Prospective data on the evolution of skills can be used to create mathematical models that predict and define competence. Computer simulation technology is rapidly evolving to provide standardized, reproducible training in all endoscopic procedures. PMID- 8193874 TI - Clinical trials. How should they be designed? AB - The fundamental principles of clinical trial design include (1) a priori formulation of a specific research question, (2) precise description of the population to be studied, (3) limitation of the effects of chance by predetermining the study hypothesis and using methods that account for multiple statistical testing, (4) calculation of the sample size necessary to answer the research question, and (5) limitation of the potential bias whenever possible through blinding and random allocation of subjects to treatment and control groups (Table 2). Although the randomized controlled trial is regarded as the gold standard for determination of efficacy of therapy, cost and sample size are frequently rate-limiting. Other techniques have been developed to supplement clinical trials and include meta-analysis, data base (observational) research, and decision analysis. In the current climate of concern over staggering health care costs and variable practice patterns, research emphases are shifting from cost containment to maximizing value of health-related services and assessing patient outcomes. PMID- 8193875 TI - A critical appraisal of antiemetic prophylaxis: are we really making progress? PMID- 8193876 TI - Suicide and euthanasia: patient attitudes in the context of cancer. PMID- 8193878 TI - Progress in controlling emesis with cancer chemotherapy. AB - Marked progress in supportive care in cancer, and in control of chemotherapy induced emesis in particular, has been accomplished over the past several years. Several effective antiemetic agents and regimens have been tested and are widely available. Emesis due to chemotherapy can now be completely controlled in the majority of patients. Progress in both clinical trials and in neuropharmacology has resulted in a new class of agents, the serotonin antagonists. These agents have an excellent therapeutic index and are well suited for a variety of clinical settings. Problems remain especially in the control of delayed emesis, in patients given several days of chemotherapy, and in radiation-induced emesis. Achieving the best antiemetic control, and at the same time having cost-effective therapy, is an ongoing challenge. PMID- 8193877 TI - Anticipatory nausea and vomiting: broadening the scope of psychological treatments. AB - Anticipatory nausea and vomiting, as a side-effect of cancer chemotherapy, is a well-recognised phenomenon known to affect a substantial minority of patients. Although explicable using a conditioning model, it may have a complex aetiology with affective and cognitive elements as well as specific pharmacological factors playing a role in its onset and maintenance. It is amenable to treatment using psychological techniques but to treat successfully it is important to understand the aetiology and formulate treatment plans according to those factors that make a significant contribution to the cause. It is suggested here that a behavioural model provides an over-simplistic conceptualization and that cognitive factors play a central role in onset. As such, treatment plans need to be broader in scope by focusing on a range of strategies to enhance coping and particularly cognitive coping techniques. More recently there has also been some indication that psychological factors may contribute to symptoms of nausea and vomiting occurring during or after chemotherapeutic infusion. Should this effect be replicated, the scope for psychological treatments within the care of patients receiving chemotherapy would be widened. PMID- 8193879 TI - Delayed emesis: a dilemma in antiemetic control. AB - Delayed emesis remains a major factor limiting successful antiemetic treatment. It is well described in patients receiving cisplatin at doses of 100 mg/m2 or greater (occurring in nearly 90% of patients), but its incidence and severity in other settings is less well known. Several studies have indicated that combinations of oral metoclopramide plus dexamethasone can decrease the incidence of this problem by one-half; however, a large number of patients remain for whom delayed emesis is their main emetic problem. To date, studies with single-agent serotonin antagonists have not shown encouraging efficacy. In addition, it appears that delayed emesis may begin as early as 16 h after chemotherapy, yielding implications for new study designs. Proper methodology for clinical studies has been demonstrated in a few well-conducted trials, which should form a basis for future research. PMID- 8193880 TI - Double beta-lactam regimen compared to an aminoglycoside/beta-lactam regimen as empiric antibiotic therapy for febrile granulocytopenic cancer patients. AB - In a prospective, randomized trial, 205 febrile episodes in granulocytopenic cancer patients were treated with ceftazidime with or without tobramycin (C +/- T), both agents being administered only if the initial granulocyte count was below 200/microliters, or ceftazidime plus piperacillin (C + P). The overall response rate was 71% (39 of 60 for C +/- T and 45 of 58 for C + P). Logistic regression analyses documented no evidence of a significant difference between the two regimens in overall treatment effect after accounting for the linear effects of potentially important variables, such as infection type and granulocyte count. Although the response rates for the subgroup of patients with bacteremias was better with the C + P regimen (P = 0.06), there was no difference in response for patients with bacteremia and profound (< 100/microliters) sustained granulocytopenia. The double beta-lactam combination demonstrated in vitro synergism in 73%; antagonism was not seen. Both regimens produced excellent serum bactericidal levels (C +/- T geometric mean peak 1:170; C + P peak 1:137) against gram-negative but not gram-positive pathogens (1:4; 1:7 respectively) that had caused bacteremia. Emergence of resistance and significant coagulopathy and/or bleeding did not occur during therapy. Antibiotic-related nephrotoxicity was noted in 7 of 95 trials in the C + P and in 6 of 89 trials in the C +/- T group (P = 0.19). The incidence of secondary infections in patients with profound (< 100/microliters) sustained granulocytopenia was lower in the C +/- T group (P = 0.04). Alimentary canal anaerobic flora preservation with C +/- T, and suppression with C + P, was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193881 TI - Pneumococcal immunity and response to immunization with pneumococcal vaccine in bone marrow transplant patients: the influence of graft versus host reaction. AB - The aim of this study was to evaluate levels and subclass distribution of pneumococcal antibodies in 40 bone marrow transplant (BMT) and 42 autologous bone marrow transplant (ABMT) recipients during the first year after transplant, and response to vaccination with a polyvalent pneumococcal vaccine. Before transplantation, 35/40 recipients of allogeneic grafts, all 42 autologous BMT recipients and 38/39 donors had adult levels of anti-pneumococcal antibodies of the IgG2 subclass. During the first year after transplantation, antibody levels decreased in 29 BMT patients while 11 retained their pretransplant antibody levels. No change was noted among ABMT patients. In the 8 BMT patients who had chronic graft versus host disease (GVHD), none showed normal levels of anti pneumococcal antibodies 1 year after BMT as compared to 11/32 without chronic GVHD. Three different response patterns were seen after vaccination of 29 BMT patients who lost immunity with a polyvalent pneumococcal vaccine. Ten patients responded with an increase in IgG2 antibodies, 8 responded with an increase in IgG1 and 11 patients did not respond at all. In the 8 patients with chronic GVHD, none responded with an increase in IgG2 antibodies and 6/8 did not respond at all. The results of this study suggest that chronic GVHD is the main factor contributing to loss of immunity to pneumococci and lack of responsiveness to vaccination with pneumococcal polysaccharides after BMT. Furthermore, the difference in capability, between BMT and ABMT recipients, of retaining anti pneumococcal activity may explain the clinical experience of severe pneumococcal infections in these patients. PMID- 8193882 TI - The Perceived Adjustment to Chronic Illness Scale (PACIS): a global indicator of coping for operable breast cancer patients in clinical trials. Swiss Group for Clinical Cancer Research (SAKK) and the International Breast Cancer Study Group (IBCSG). AB - Subjective well-being is a major aspect of quality of life and is therefore increasingly used as an endpoint in clinical trials. It is influenced to a great extent by the complex process of coping with the disease and its treatment. Assessment of coping is methodologically demanding, especially in large clinical trials. We therefore developed a single-item measure, the Perceived Adjustment to Chronic Illness Scale (PACIS), as an indicator of coping, complementary to other scales related to quality of life. We sought to validate this instrument in a subgroup of 121 Swiss patients participating in the International Breast Cancer Study Group (IBCSG) adjuvant trials. At months 3 and 6 of adjuvant treatment PACIS showed a distinct pattern of highly significant rank correlations with several disease- and treatment-related problem areas from the Herschbach coping inventory (FBBK); 42% of the variance of PACIS at month 3 was explained by the FBBK (P = .0001). The portion of explained variance was considerably higher for the Italian- (70%) than for the German-speaking (30%) subgroups. Patients who rated more effort to cope with their disease on PACIS indicated more frequent use of 3 of 15 coping strategies in relation to psychological distress. These were "crying and becoming desperate", "taking tranquillizers and alcohol" and "other people are far worse off". These three coping strategies may define a high-risk group for poor psychosocial outcome. Patients whose PACIS scores showed that it required less effort to cope tended to use the strategy "seeing a positive side of the problem". We conclude that PACIS can be used as a global indicator of the coping process in large multicultural clinical trials of adjuvant therapy for breast cancer. PMID- 8193883 TI - Patient assessment of a combined medical and nursing preparation to cytotoxic chemotherapy. AB - At Auckland hospital there is a combined medical and nursing preparation for patients receiving cytotoxic chemotherapy. The aim of the current study was to assess whether patients felt that this combined approach had prepared them adequately for chemotherapy. Patients were asked to complete three questionnaires anonymously at different times in their treatment programme: immediately prior to chemotherapy, after three cycles of chemotherapy and 2 months after completion of chemotherapy. A high level of satisfaction with the programme was demonstrated: 68% of patients thought the orientation programme had prepared them "very well", 32% "adequately" and none "poorly" for their chemotherapy. Separate interviews with medical and nursing staff were thought a "good idea" by 86% of patients and only 1 of 100 medical and 100 nursing interviews was assessed as "not worthwhile". This study suggests that a combined medical and nursing preparation is a worthwhile practice in preparing patients for cytotoxic chemotherapy. PMID- 8193884 TI - Fluconazol plus ofloxacin in prophylaxis of infections in patients with acute leukemia: a comparative study. AB - In a retrospective study the incidence of infections, number of afebrile days, duration of antimicrobial chemotherapy, and cost of antibacterials and antimycotics were compared in two groups of patients. One was a group of 57 patients who received no prophylaxis during induction remission therapy of acute leukemia treated in 1989-1990, the second was a group of 22 patients treated in 1991 where prophylaxis with fluconazol and ofloxacin was administered. For ethical reasons pertaining since 1991, when prophylaxis became mandatory, the study was not randomized. A decrease in the number of febrile days, the cost of antimicrobials and the duration of treatment with antibiotics and antimycotics was observed in the group receiving fluconazol and ofloxacin. PMID- 8193885 TI - Clinical evaluation of fast spin echo sequences for cranial magnetic resonance imaging at 0.5 tesla. AB - Fast spin echo (FSE) sequences enable T2-weighted MR scans to be obtained in a fraction of the time necessary for conventional SE sequences with long TR and long TE. Comparison has been made of a FSE sequence (TR = 4000 ms, effective TE = 100 ms, 2 NEX) with the T2-weighted SE sequence (TR = 2000 ms, TE = 90 ms, 1-2 NEX) normally used in 35 patients referred for cranial MRI. Contrast-to-noise ratios (CNR) for grey:white matter and brain:CSF on the FSE sequence compared favourably with variable echo (VE) sequences which take up to three times as long to acquire. Although the conspicuity of some pathological lesions such as multiple sclerosis plaques was inferior to that of conventional T2-weighted SE scans, no lesions were missed on FSE scans. The FSE sequence was more prone to movement artefacts. The benefit of the markedly increased patient throughput made possible by using the FSE sequence outweighs the slight reduction in sensitivity for small lesions. PMID- 8193886 TI - Ultrasound findings following laparoscopic cholecystectomy. AB - This study was set up to find the incidence of fluid collections in asymptomatic patients following laparoscopic cholecystectomy. Patients had an ultrasound scan on the first postoperative day and approximately 1 week later. Seven of 25 patients (28%) had a total of nine collections on the first postoperative day. Five had resolved by the follow-up scan and two patients developed new collections by the 1 week scan. None of the patients had significant postoperative symptoms. We emphasize the high incidence of ultrasonically detectable fluid collections in asymptomatic patients following laparoscopic cholecystectomy, encourage caution in attributing postoperative morbidity to such findings, and suggest that repeat scanning may be helpful in patient management. PMID- 8193887 TI - Magnetic resonance assessment of age-related development of the sphenoid sinus. AB - Magnetic resonance images of the sphenoid sinus in 401 patients under 15 years old were reviewed to establish normal age-related standards. T1-weighted sagittal and T2-weighted axial scans were evaluated for bone marrow conversion, development of pneumatization, spatial enlargement and septation of the sphenoid sinus. The sphenoid sinus had a uniformly low signal intensity (red bone marrow) on T1-weighted images in all children less than 4 months old. Signal intensity changes from hypointense to hyperintense (bone marrow conversion) started at the age of 4 months. Onset of pneumatization was observed in 12% of the patients at age 13-15 months. By age 43-48 months, 85% of the patients showed pneumatization of the anterior part of the sphenoid bone. Pneumatization was complete in all patients older than 10 years. Enlargement of the sinus showed a characteristic profile in each dimension. Median septation was observed irregularly with age, with a maximum of 77%. Septum variants were noticed between 4.5% and 20%. Because paediatric sinus disease is a challenging problem in children, these results may be useful as baseline standards of normal age-related development of the sphenoid sinus during childhood. PMID- 8193888 TI - Comparison of spiral-acquisition computed tomography and conventional computed tomography in the assessment of pulmonary metastatic disease. AB - In a prospective study, spiral-acquisition computed tomography (SACT) of the thorax was evaluated in 104 patients with extrathoracic malignancy and suspected pulmonary metastases, and was directly compared with conventional computed tomography (CCT) in 23 patients. The following parameters were assessed: lesion detectability; the effect on lesion detectability of reconstruction of scans at 5 mm and 10 mm slice increments; breathing artefact and slice misregistration. The radiation dose of the two techniques was measured using thermoluminescent dosimeters placed within an anthropomorphic chest phantom, and the visibility of simulated metastases inserted into the phantom was also compared using CCT, standard SACT and SACT with pitch greater than 1.0. Where metastases were present, SACT scans showed significantly better lesion detectability than CCT scans (p < 0.001). Image reconstruction of SACT data at 5 mm increments conferred no significant advantage in lesion detectability over 10 mm increment reconstructions. Compared with CCT, SACT scans showed reduced breathing artefact, and a complete absence of slice misregistration (p < 0.01). Phantom measurements of radiation dose and resolution were similar for both techniques. Increasing the pitch of the spiral in SACT caused only a small decrease in phantom resolution, but with the advantage of a reduction in the radiation dose. Spiral-acquisition CT is superior to conventional CT for the assessment of pulmonary metastatic disease. PMID- 8193889 TI - Three-dimensional computed tomography cholangiography: a new technique for biliary tract imaging. AB - Knowledge of the segmental anatomy and intersegmental biliary connections is an essential prerequisite to the effective management of patients with complex biliary strictures. Three dimensional (3D) imaging has the ability to demonstrate complex anatomical relationships that are difficult to appreciate on simple non invasive two dimensional (2D) imaging. Our aim was to develop a technique for accurate, non-invasive 3D computed tomography (CT) cholangiography. Contiguous 4 mm CT sections were obtained through the liver during a dynamic bolus of 200 ml IV contrast. 3D surface reconstructions were then performed, the biliary system was isolated from surrounding hepatic parenchyma using segmentation and contrast threshold algorithms. 14 patients (six females, eight males, median age 68 years (range 48-82)) were studied. 13/14 had malignant biliary obstruction and one had obstruction secondary to a pancreatic pseudocyst. Obstruction was at the liver hilum in eight, the common bile duct in five and the common hepatic duct in one. Four patients had biliary endoprostheses but were symptomatic from inadequate drainage. There was good demonstration of the biliary anatomy, obstructed segments and intersegmental biliary connections in 13/14; irregular biliary dilatation secondary to primary sclerosing cholangitis rendered interpretation difficult in one. 3D cholangiography provided a useful adjunct to other imaging techniques. In particular, in patients with complex hilar strictures it aided implementation of appropriate interventional drainage procedures. PMID- 8193890 TI - Colonic complication of acute lymphoblastic leukaemia. AB - We present four unusual colonic complications of acute lymphoblastic leukaemia which occurred during the early induction period of chemotherapy. These included a transverse colitis, a haemorrhagic proctitis, a caeco-colic intussusception and an ileo-colic intussusception complicating typhlitis. Although complications are rare, they should be considered in the differential diagnosis of abdominal pain in children undergoing chemotherapy. PMID- 8193891 TI - Imlink and continuing medical education: the use of an image transfer system to broadcast teaching cases nationally. AB - Imlink, a personal computer based image storage and transfer system, has been used regularly in Oxford since 1989, primarily to transmit computed tomography (CT) brain scans to the regional neurosurgery centre for management advice. Recently this system has been used to send a weekly educational programme (CT and magnetic resonance imaging neuroradiology cases) to district general hospitals. PMID- 8193892 TI - Measuring image texture to separate "difficult" from "easy" mammograms. AB - We are investigating computerized techniques for sorting mammograms according to whether the breast tissue is fatty or dense. The hypothesis is that areas of dense tissue are a major factor in making certain mammograms harder for both radiologists and computers to interpret. Being able to identify dense mammograms automatically could permit better use of the time and skills of expert radiologists by allowing the difficult mammograms to be examined by the most experienced readers. In addition, the scope for computer-aided detection of abnormalities might be increased by concentrating on the easier, fatty mammograms. The mammograms used in the experiment were classified independently by two radiologists, who agreed in almost all cases. A number of local statistical and texture measures were then computed for patches from digitizations of these mammograms. One of the measures (local skewness in tiles) gives a good separation between fatty and dense patches. This measure has been incorporated into an automated procedure that separates off approximately two thirds of the fatty mammograms. This finding has been replicated on mammograms taken from a UK screening programme. The relationship between the fatty/dense distinction and the classification proposed by Wolfe is discussed. PMID- 8193893 TI - A clinical comparison between conventional and digital mammography utilizing computed radiography. AB - Previous work utilizing a specially designed mammographic test object has indicated that the image quality of computed radiography (CR) approaches that of a conventional film-screen technique of equivalent radiographic speed. In an attempt to correlate these results with the clinical situation a subjective rating study of the primary physical parameters of noise, sharpness, and contrast has been conducted. Using a randomized viewing sequence two radiologists experienced in mammography were asked to score these parameters utilizing a 5 point scale. A total of 138 images was used, 62% containing no abnormalities and 38% containing either microcalcifications, masses or both. Additionally, the observers scored their confidence of correct classification, and these results were then used to construct receiver operating characteristic (ROC) curves. The subjective rating of the physical parameters results produced similar results to those obtained using the test object, with CR images providing greater contrast than film. The resolution of CR, however, was lower than for film. Overall the noise levels were similar for both modalities, but the digital images occasionally contained high levels of dust artefacts. In one case these artefacts were mistaken for a cluster of microcalcifications. The test object results and the parameter rating results indicate that CR approaches the performance of film screen images. Statistically the ROC curves produced indicate CR images to be comparable to the film-screen combination. This may be because the increased contrast compensates for resolution limitations and these findings correlate with our clinical experience. PMID- 8193894 TI - Can 99Tcm HMPAO leucocyte scintigraphy distinguish between Crohn's disease and ulcerative colitis? AB - This paper has retrospectively analysed the ability of 99Tcm HMPAO leucocyte scintigraphy to distinguish Crohn's disease from ulcerative colitis. The diagnostic criteria were established by reviewing 99Tcm HMPAO leucocyte scintigrams in 123 patients with histologically proven Crohn's disease (83) or ulcerative colitis (40). Uptake in the right iliac fossa with or without other segments of colon, irregular bowel uptake, small bowel uptake or colonic activity with rectal sparing were all strongly suggestive of Crohn's disease. Left sided colitis was found to indicate ulcerative colitis. Total colitis occurred in both ulcerative colitis and Crohn's disease. The criteria were later tested in an additional 62 patients with excellent results (accuracy 98%). In 63 patients in whom the results of barium radiology were also available, the accuracy of scintigraphy was higher (93% and 83%, respectively). We conclude that 99Tcm HMPAO leucocyte scintigraphy can accurately distinguish between Crohn's disease and ulcerative colitis in a large proportion of cases and appears to be more reliable than conventional radiology. PMID- 8193895 TI - A comparison of radiation dose in examination of the abdomen using different radiological imaging techniques. AB - Typical radiation doses for abdominal examinations were determined for field sizes and entrance doses commonly selected on image intensifier based digital radiographic systems. In addition, measurements were also performed using conventional film-screen methods, a 100 mm camera combination and a phosphor storage computed radiography system. Both antero-posterior and postero-anterior projections were assessed. An anthropomorphic phantom loaded with lithium fluoride thermoluminescent dosimeters was used to measure entrance surface doses. Organ equivalent doses, deduced using normalized organ dose data, were used to calculate effective dose and effective dose equivalent. A comparison of the imaging techniques on the basis of effective dose indicated that significant dose reductions (by approximately a factor of 3) may be expected if the abdomen is imaged using a postero-anterior rather than an antero-posterior projection for a given imaging system. If digital imaging systems are used instead of a conventional film-screen technique, patient effective dose for a given projection can be lower by at least a factor of 5. PMID- 8193896 TI - Estimation of effective dose from dose-area product measurements for barium meals and barium enemas. AB - The International Commission on Radiological Protection has recommended the use of a new dose quantity "effective dose". The doses to 22 organs of the human body are required for a formal calculation of this quantity. This paper shows that a quick estimate of the effective dose received by a patient from a barium meal or a barium enema can be made by multiplying the measured dose-area product for the complete examination by an appropriate conversion coefficient. Despite the varied techniques used for barium examinations, such an estimate is unlikely to be in error by more than 25%. PMID- 8193897 TI - Technical note: radiological insertion of an implantable drug delivery system. AB - A fully implantable drug delivery system has been shown to overcome many of the problems of long-term venous access. Traditionally these have required surgical implantation but we describe a simple, cost-effective and successful technique for the percutaneous insertion of an implantable vascular device (Vascuport, Ohmeda) in the angiography suite under local anaesthesia. It was successful in all 19 patients in whom it was attempted, with only one minor complication. We recommend that the procedure should be performed in X-ray departments using screening and conventional guidewire techniques. PMID- 8193898 TI - Technical note: the measurement of mammographic room protection. AB - Owing to the inherent design of mammographic X-ray tubes, transmission measurements through the surrounding protective barriers are difficult to obtain using the primary beam. An alternative method has been developed which employs an iodine-125 source. Transmission measurements were obtained through common building materials using both the iodine-125 source and a mammographic X-ray beam generated at 35 kVp. Measurements were converted into an aluminium equivalence, from which correction factors were calculated to convert the aluminium equivalence determined using iodine-125 to the true aluminium equivalence. Average correction factors for samples of glass, chipboard and plasterboard were 1.10, 0.75, and 0.85, respectively. PMID- 8193899 TI - Case report: rectal infarction after abdominal aortic surgery. AB - Full thickness ischaemic colitis complicates approximately 1-2% of abdominal aortic procedures. Ligation of the inferior mesenteric artery and hypotension are recognized as causative factors. It is not, however, widely appreciated that ischaemic proctitis may also rarely complicate aortic surgery, especially after complex procedures or if there has been additional interruption to the internal iliac circulation. We report a case of rectal necrosis following repair of a thrombosed aortic aneurysm in which plain X-ray appearances aided the diagnosis. PMID- 8193900 TI - Case report: new sonographic finding in renal infarction. AB - We observed a unique sonographic finding in a patient with right global renal infarction associated with an abdominal aortic dissection. Sonography in the acute phase revealed a highly echogenic and thickened perirenal fascia without demonstrable abnormality of the renal parenchyma. This finding may be helpful in the early diagnosis of renal infarction by routine sonography. PMID- 8193901 TI - Case report: intraperitoneal metastases from testicular germ cell tumour. AB - We report a patient with intraperitoneal metastases following treatment for seminoma. This is an unusual site of spread and was accompanied by transformation of tumour morphology. PMID- 8193902 TI - Case report: salvage fractionated high dose rate after-loading brachytherapy in the treatment of a recurrent tumour in the middle ear. AB - Re-irradiation of previously irradiated head and neck sites is associated with a high complication rate. In an attempt to reduce this complication risk, multiple fractions of high dose rate (HDR) intracavitary irradiation were used in a young patient who had developed recurrent transitional cell carcinoma in the tympanic cavity one year after radical radiotherapy. After gross surgical removal of the tumour, an afterloading probe was placed into the middle ear by a surgical approach. In 11 treatments of 3 Gy each over 4 days, a total dose of 33 Gy was delivered to a spherical volume, 1.7 cm in diameter. The patient was 24 months free of disease at the start of 1993. Audiometry shows no severe deterioration of hearing. We concluded that fractionated HDR brachytherapy can be used to achieve local control in small volume recurrences at previously irradiated sites, without the inevitability of complications. PMID- 8193903 TI - Case report: squamous cell carcinoma of the skin in both palms, axillary node, donor skin graft site and both soles--associated hyperkeratosis and porokeratosis. AB - A 74-year-old woman presented with skin squamous cell carcinomas on both palms, ankles and soles. The patient also had biopsy-proven porokeratosis. There was hyperkeratosis of the palms and soles. The left palm cancer was excised and skin grafted, but recurred. A nodule in the scar of the donor site of the skin graft in the left upper arm was biopsy-proven squamous cell carcinoma. A metastatic left axillary lymph node was excised. There were no palpable metastatic lymph nodes in either the groin or right axilla. All cancers were irradiated and disappeared, as did the incidentally irradiated hyperkeratosis. Porokeratosis may be associated with skin squamous cell carcinoma, yet in this case porokeratosis could not be identified in the heavily hyperkeratotic palms and soles. Despite poor prognostic signs, i.e. the location in the palm, and metastasis, the patient has done well so far. PMID- 8193904 TI - Case of the month: a pensioner's plight. PMID- 8193905 TI - The selection of age groupings for the results of radiation dose surveys in paediatric radiology. PMID- 8193906 TI - The safety of outpatient arteriography using 3F catheters. PMID- 8193907 TI - Efferents from the suprachiasmatic nucleus to basal forebrain nuclei in the green treefrog (Hyla cinerea). AB - Injections of horseradish peroxidase (HRP) into the eye, striatum, preoptic area, or ventral hypothalamus of the green treefrog (Hyla cinerea) demonstrated an indirect retinal pathway to each basal forebrain region via the suprachiasmatic nucleus (SCN). Intraocular injections resulted in HRP-filled fibers within the ventral portion of the SCN bilaterally. Apparent en passant and terminal swellings on these fibers were seen adjacent to SCN cells. Cells in both the ventral and dorsal portions of the SCN were retrogradely filled following each of the forebrain injections, but the relative distributions of filled cells were different. The striatum receives a bilateral projection mainly from cells in the ventral portion of the SCN. A small ipsilateral projection from this same SCN region reaches the ventral hypothalamus. The SCN projection to the preoptic area arises from a more uniform distribution of cells, with the majority located in the ipsilateral dorsal region of the nucleus. The striatum is believed to be involved in orientation responses, while the preoptic area and ventral hypothalamus regulate gonadal activity related to reproduction. Each of these areas receives auditory input carrying information about acoustic communication signals, social cues important for coordinating reproductive activity. Input from the SCN could provide these same basal forebrain centers with information about the photic environment, an important environmental cue regulating reproduction. PMID- 8193908 TI - Cytoarchitecture and staining for acetylcholinesterase and zinc in the visual cortex of the Parma wallaby (Macropus parma). AB - Cytoarchitecture and distributions of acetylcholinesterase-containing fibers and zinc-containing neuropil are described in the primary visual cortex of a metatherian, the Parma wallaby (Macropus parma). Although some cytoarchitectural features of layer III suggest that a subdivision and a corresponding layer IIIa-c terminology may be employed, neurochemistry is more concisely described using a simple layer I-VI terminology. Horizontal acetylcholinesterase-containing fibers in layer I take on a vertical course as they pass through layer II to form a reticulate pattern in upper layer III. Fibers gather into vertical groups in lower layer III and, markedly, in layer IV. No dominant orientation is seen in layer V, whereas an horizontal course is often seen in layer VI. Zinc-containing neuropil is very dense layers I, II and upper III, where particles are homogeneously distributed. Particles begin to form strands in lower layer III and form conspicuous vertical clusters in an otherwise almost unstained layer IV. There is a sharp transition to a densely and homogeneously stained layer V, a decrease in staining intensity in layer VI, and a further decrease within layer VI towards the white matter. The distribution of acetylcholinesterase-containing fibers in M. parma, a metatherian representative, adds to the number of species specific patterns observed in eutherians. The distribution of zinc-containing neuropil in M. parma resembles the consistent pattern seen in eutherian species. Thus, pathways incorporating zinc, as a putative neuromodulator of excitatory amino acid receptor responses, may be organized similarly in the cortex of meta- and eutherians. PMID- 8193909 TI - An experimental re-evaluation of the primary visual system of the European chameleon, Chamaeleo chameleon. AB - The retinofugal projections of the chameleon were investigated by means of autoradiography, horseradish peroxidase and fluorescent techniques after intraocular injection of tracers. An ipsilateral contingent of visual fibers and projections is absent. The retinal fibers decussate completely in alternating fascicles at the optic chiasma and course to terminate in two hypothalamic nuclei (nucleus suprachiasmaticus and nucleus opticus periventricularis hypothalami posterior), six thalamic nuclei (nucleus ovalis, nucleus geniculatus lateralis dorsalis partes lateralis and medialis, nucleus geniculatus lateralis ventralis, lateral part of nucleus dorsolateralis anterior, and nucleus ventrobasalis), four pretectal nuclei (nucleus griseus tectalis, nucleus lentiformis mesencephali, nucleus geniculatus pretectalis and nucleus posterodorsalis), the optic tectum (stratum griseum et fibrosum superficiale) and the tegmental nucleus opticus tegmenti. Our findings are, in general, compatible with previous descriptions of the primary visual system in other species of lizards. However, they indicate three features particular to chameleons: first, the total absence of an ipsilateral retinofugal projection; second, the existence of an additional hypothalamic visual center located in the posterior mediodorsal hypothalamus; and third, the large size of nucleus opticus tegmenti. These features are discussed in terms of the taxonomic position of chameleons with respect to other lizards. PMID- 8193910 TI - Lexicality and modality effects on evoked potentials in a memory-scanning task. AB - Event-related potentials, as well as reaction times and performance accuracies, were recorded from normal young adults during the performance of a memory scanning task, in response to the first and second items of the memorized set and to the probe. Stimuli included computer-generated digits, presented by earphones as speech (lexical auditory) or on a screen (lexical visual), meaningless voices (nonlexical auditory) with precisely the same frequency contents as the digits, or meaningless shapes with the very same colors and contours as the digits (nonlexical visual). The evoked potentials' late positivity (P3) to memorized items was earlier to auditory than to visual stimuli. P3 to memorized items and to probes was earlier to lexical than to nonlexical stimuli. P3 amplitudes to both memorized items and probes were smaller with auditory stimuli. Assuming P3 latency to reflect processing time and amplitude to reflect attentional allocation (effort) to the task-relevant stimuli, the results support phonological representations during processing in short-term memory, with nonauditory and nonlexical stimuli requiring more processing time and effort. A significant electrode x modality x lexicality interaction may suggest that stimuli of different modalities and lexicality involve variations in the relative contributions of the brain structures involved in their processing. PMID- 8193911 TI - Wernicke and Alzheimer on the language disturbances of dementia and aphasia. AB - Signs of language dysfunction in dementia of the Alzheimer's type (DAT) and in the aphasic syndromes of transcortical sensory aphasia and Wernicke's aphasia are superficially similar. The unresolved question concerning the extent to which the language disturbances of DAT are "aphasic" is linked to a more fundamental question concerning the relation of language to thought, given that aphasia is often defined as language disturbance without disturbance of intellect, and dementia as dissolution of intellectual function, of which language forms an integral part. In this paper we explore the historical roots of today's debate by analyzing the original case studies of Wernicke (1874) and Alzheimer (1907, 1911). Although each of these neurologists described similar patterns of language disturbance, they drew different conclusions. Wernicke argued for a distinction between language and thought and between the language disturbances of aphasia and those of dementia. Alzheimer continued the then dominant paradigm of aphasia in describing the language disturbances of his demented patients as aphasic. Paradoxically his conclusion makes him appear, in contrast to Wernicke, to argue for the identity of the language disturbances of aphasia and dementia. Yet he himself acknowledged that the presence of focal language symptoms arising from diffuse degenerative pathology was indeed problematic. We conclude that today's discussion could profitably be refocused on the question which emerges from the original works of Wernicke and Alzheimer, which Alzheimer himself asked, and which remains unanswered: How can diffuse cerebral pathology give rise to a pattern of language deficit virtually identical to that of a focal lesion? PMID- 8193912 TI - A note on prepositions in agrammatism. AB - In this note, prepositions in the spontaneous speech of eight German agrammatics are investigated. Contrary to predictions derived from Grodzinsky (1990), no differential error pattern of governed and ungoverned prepositions could be found. PMID- 8193913 TI - Modeling clinical judgment: a reanalysis of data from Wilson and Risucci's (1986) paper "A model for clinical-quantitative classification. Generation I: Application to language disordered preschool children". PMID- 8193914 TI - The possible role of asymmetric laryngeal innervation in language lateralization: points for and against. PMID- 8193915 TI - Neural development following NMDA administration in the rat: an electron microscopic examination of the occipital neocortex layer I. AB - Recent research has suggested that the N-methyl-D-aspartate (NMDA) receptor plays a role in numerous activity dependent models of synaptic plasticity. The current research attempted to determine whether chronic activation of the NMDA receptor could induce alterations in synaptic development. An examination of acute NMDA toxicity indicated that rats become increasingly resistant to NMDA over development. Male rats aged 8 days were administered one, 1/10 LD50, SC injection of either NMDA or saline vehicle every 8 h until 18 days of age and were sacrificed 2 days later. Chronic administration of NMDA produced no changes in body or brain weight, the length of synaptic contacts, or the number of synapses per unit area in the neocortical molecular layer. There was a significant 10% increase in the depth of the occipital cortex molecular layer, yielding a 15% increase in the estimated total number of synapses within that area. These results suggest that activation of the NMDA receptor is capable of altering certain aspects of neural development, while other components are not affected. PMID- 8193916 TI - The increased ethanol preference in rats induced by choice, darkness, or drugs is reduced by ritanserin. AB - We tested the hypothesis that ritanserin, a serotonin S2 antagonist, reduces voluntary and induced forms of ethanol drinking. We gave 10 mg/kg ritanserin IP or SC to groups of rats given either a) a free choice between 3% ethanol and water, or b) kept in the dark for 5 weeks and given a choice between a range of ethanol concentrations (3-25%) and water, or c) implanted with osmotic pumps filled with tetrahydro-beta carboline and given a choice between a range of ethanol concentrations and water. In each case, ritanserin significantly reduced ethanol consumption and ethanol preference for 8-10 days after the last injection. PMID- 8193917 TI - Effect of a phase advance of the light/dark cycle on pineal function and circadian running activity in individual rats. AB - Circadian rhythms of urinary 6-sulphatoxy-melatonin excretion and spontaneous wheel-running activity were monitored in individual male Wistar albino and hooded rats entrained to a 12 h L:12 h D photoperiod, before and after an 8 h phase advance of the light cycle. The pigmented hooded strain commenced melatonin metabolite excretion 2 h after darkness, whereas the albino rats did not excrete detectable amounts until 4 h of darkness had elapsed (p < 0.05). There was no correlation between the time of onset of spontaneous wheel-running activity and the onset of excretion of 6-sulphatoxymelatonin under entrained conditions. When the photoperiod was advanced by 8 h, the albino rats took a median of 4 days (range 2-10 days) to establish a normal phase angle for the onset of 6 sulphatoxymelatonin excretion in contrast to the pigmented rats, which took in excess of 10 days to entrain. Albino rats reentrained running activity significantly earlier than pigmented rats (8 days: range 6-9 days), compared to 10 days (range 8 to > 12 days). There was no consistent relationship between the pineal and running rhythms with respect to the time taken to entrain following a lighting phase shift. All rats entrained the 6-sulphatoxymelatonin rhythm by advancing the onset of excretion in contrast to the running rhythm where three rats reentrained by advancing, three by delaying, and in four, the direction of entrainment could not be accurately determined. In two of the animals (both albino), there was unequivocal evidence that the 6-sulphatoxymelatonin rhythm and running reentrained in different directions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193918 TI - Crosstalk in the magnocellular system during osmotic stimulation of one supraoptic nucleus. AB - Neural connections linking the four magnocellular nuclei, i.e., the paired supraoptic (SON) and paraventricular (PVN) nuclei, may contribute to the simultaneous and parallel changes in firing patterns of oxytocinergic neurons during reflex milk ejection. To investigate these neural connections in the absence of suckling, intranuclear release of oxytocin (OT) was stimulated by microdialysis of hypertonic CSF containing 1 M NaCl (HS-CSF) into the right SON area and glucose metabolism of both SONs and PVNs and the neural lobe of virgin and lactating (10-12 day) rats was mapped by the autoradiographic [14C]deoxyglucose (DG) method. OT in the microdialysates and in plasma, obtained before and after 80-90 min of dialysis with CSF or HS-CSF, was quantified by RIA. In both virgin and lactating rats, microdialysis of HS-CSF unilaterally into the SON area significantly (p < 0.05) increased release of OT in the nucleus and into plasma, which was associated with enhanced (p < 0.05) metabolic activity in the ipsilateral and contralateral SON and the neural lobe but not in either PVN. Compared with virgins, lactating rats were less active, had lower (p < 0.05) glucose utilization in the hypothalamo-neurohypophysial system, and less (p < 0.05) OT in plasma during microdialysis of HS-CSF into the SON area. The osmotic stimulus did not activate neural structures (suprachiasmatic and medial amygdaloid nuclei) near the SON in either hemisphere. Thus, neural connections or, less likely, transport of OT via the subarachnoid space, may function to recruit activation of cells in the contralateral SON following hypertonic stimulation of cells in the other SON. PMID- 8193919 TI - Blood flow increase in the orofacial area of humans induced by painful stimulation. AB - The purpose of this study was to investigate if painful stimulation produces blood flow changes in the tooth pulp and the facial skin in humans. Also, we attempted to find out if the possible blood flow changes induced by painful stimulation could be explained by central sympathetic and parasympathetic reflex mechanisms, by an antidromic activation of nociceptive axons (axon reflex), or by a change in central cardiovascular parameters. Laser Doppler flowmeter was used to assess the blood flow changes. Electrical tooth pulp stimulation at painful intensities induced a blood flow increase in the ipsilateral lip adjacent to the stimulus site, and vice versa. Nonpainful stimulation had no effects. Painful thermal stimulation of the upper lip also produced an increase in the blood flow of the ipsilateral upper incisor. The blood flow changes in the lip produced by dental stimulation were not correlated with changes in systemic blood pressure or heart rate. Painful electrical stimulation of the hand did not induce any changes in the pulpal blood flow, whereas painful dental stimulation produced a blood flow decrease in the finger but no change in the contralateral lip or cheek. In monkey experiments a regional block of the central conduction of the inferior alveolar nerve at the level of the mandibular foramen produced varying results: the blood flow increase in the lower incisor produced by noxious thermal stimulation of the ipsilateral lower lip was not abolished in two experiments but was abolished in other two experiments. It is concluded that painful stimulation can induce significant increases in the blood flow of the orofacial regions in humans. This increase is predominantly restricted to the region adjacent to the stimulus site and cannot be explained by changes in the central cardiovascular parameters. Central neuronal reflex mechanisms and an axon reflex may both underlie these blood flow increases. PMID- 8193920 TI - Differences in the ovulatory response to unilateral lesions in the preoptic or anterior hypothalamic area performed on each day of the estrous cycle of adult rats. AB - The effects of a unilateral lesion made on the right or left side of the preoptic area (POA) or anterior hypothalamic area (AHA) made on each day of the estrous cycle, were analyzed. Ovulation rate decreased among the animals with a lesion performed on the day of estrous on the right side of POA (1/7 vs. 7/7, p < 0.05) and in animals with a lesion on diestrus-1 on each side AHA (4/9, 4/9 vs. 7/7, p < 0.05). Ovulation was restored by GnRH injection, while estradiol benzoate administration restored ovulation only in rats with a lesion on the right side of POA or AHA. We suggest that the participation of POA and AHA in the regulation of ovulation is asymmetric, lateralized, and changes during the estrous cycle. The estrogen-positive feedback needs the integrity of the left side of AHA on diestrus-1. PMID- 8193921 TI - Not only osmotic stress but also repeated restraint stress causes structural plasticity in the supraoptic nucleus of the rat hypothalamus. AB - Magnocellular neuroendocrine cells (MNCs) in the supraoptic nucleus (SON) of the hypothalamus have been known to undergo dramatic structural changes during chronic stimulation such as osmotic stress. In the present study, we examined whether this anatomical neural plasticity is associated with an another stress, such as restraint. Rats were chronically stimulated by either dehydration with 2% saline drinking instead of water or daily restraint with leg immobilization. The structural reorganizations of MNCs in the SON were analyzed morphometrically with use of light and electron microscopy. The results were compared to control animals that had free access to water and food. In restraint rats, the soma size of both oxytocin (OXT) and arginine vasopressin (AVP) neurons was enlarged, and the percent of soma-somatic/dendritic membrane contact (juxtaposition) was elevated significantly. The number of total synapses per 100 microns soma membrane was not changed, although soma profiles were enlarged. However, the number of multiple synapses (which contacted with more than one postsynaptic element) per 100 microns soma membrane was significantly increased. Similar structural changes were observed in dehydrated animals, and the degree of morphological changes was stronger than the restraint one. These findings indicate that NMCs undergo structural plasticity during not only osmotic stress but also restraint stress. PMID- 8193922 TI - Endothelin-3 stimulates phosphoinositide hydrolysis in the subfornical organ and median eminence of the rat brain. AB - The effect of Endothelin-3 on phosphoinositide turnover was studied in two brain structures, the subfornical organ and median eminence. ET-3 increased inositol monophosphate accumulation in the range 1 nM to 2 microM. Basal and stimulated InsP1 accumulation increased linearly during 1 h. The PI response elicited by ET 3 was dependent on the presence of extracellular Ca++. Removal of extracellular Ca++ or addition of Cd++ resulted in a marked decrease in ET-3-stimulated InsP1 accumulation. On the contrary, phosphoinositide hydrolysis was not changed by the calcium channel blockers nifedipine or amlodipine; however, it was decreased by amiloride, a Na+/H+ antiporter or Na+/Ca++ exchange blocker. ET-3 induced PI breakdown was inhibited in, a dose-dependent manner, by neomycin, an inhibitor of phospholipase C. These findings further support the hypothesis that stimulation of PI turnover constitutes one of the signalling pathways of ET-3 in the central nervous system, possibly through the stimulation of a specific receptor coupled to phospholipase C. PMID- 8193923 TI - Expression of c-fos in the rat cerebral cortex after focal ischemia and reperfusion. AB - Time-dependent changes in c-fos-like immunoreactivity (c-fos-LI) were studied in the rat during focal cerebral ischemia and reperfusion after middle cerebral artery (MCA) occlusion. In the permanent ischemia model, the levels of c-fos-LI increased for the first 30 min of ischemia in neuronal nuclei in the lesioned hemisphere. They reached a maximum at 60 min. The level in the parietal cortex (PC) diminished considerably after 120 min, and in the cingulate cortex (CC) it gradually decreased to near the control value at 180 min. Regional cerebral blood flow (rCBF) in the PC fell to 32% and that in the CC fell to 64% of pre-ischemic values after MCA occlusion. Reperfusion induced strong expression of c-fos-LI in the PC and CC after 6 h of reperfusion that followed 30 min of ischemia. The c fos-LI was effectively reduced by preadministration of the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine (100 mg/kg, IP). These findings suggest that the expression of c-fos after ischemia may be immediately activated through NMDA receptors and may spread to surrounding regions in a manner sensitive to reductions in rCBF. Reperfusion after ischemia also appears to cause activation of expression of c-fos and of intracellular signal transduction. PMID- 8193924 TI - GABA inhibition of lateral hypothalamic neurons: role of reticular thalamic afferents. AB - GABA and reticular thalamic (RT) stimulation induced inhibition of lateral hypothalamic (LH) neuronal activity was studied to determine if RT inhibitory input to the LH is mediated by stimulation of GABA receptors. Seven barrel electrodes were utilized to record simultaneously from the LH during microiontophoretic application of GABA, glycine, bicuculline, picrotoxin, and electrical stimulation of the RT. GABA produced an ejection current-related decrease in LH neuronal activity that was antagonized, in a dose-related manner, by the simultaneous administration of picrotoxin or bicuculline. LH neurons were much less sensitive to glycine inhibition which also was relatively insensitive to the GABA receptor antagonists. RT electrical stimulation provided a short latency inhibitory input to LH neurons that was mimicked by the microiontophoretic administration of GABA. In addition, the microiontophoretic application of picrotoxin or bicuculline blocked the RT stimulation induced inhibition of LH neuronal activity. These data indicate that the inhibitory effects of both GABA and RT synaptic inputs onto LH neurons are mediated by stimulation of GABAA receptors and substantiates the involvement of GABA as the inhibitory transmitter of thalamic to hypothalamic projections. PMID- 8193925 TI - Preparation of isolated perfused ground squirrel brain. AB - This paper describes preparation of the isolated brain of hibernating ground squirrel maintained by intraarterial perfusion. This technique allows a long-term survival (about 3 days) of the isolated brain of adult animals. The preparation viability was assessed by extracellular investigation of stability of structure specific electrical activity. The areas investigated include neocortex, hippocampus, thalamus, hypothalamus, and brain stem. PMID- 8193926 TI - Morphological and GAD immunocytochemical properties of the dorsal lateral geniculate nucleus in a reptile. AB - Morphological and glutamic acid decarboxylase (GAD) immunocytochemical properties of the dorsal part of the lateral geniculate nucleus were investigated in reptiles, Caiman crocodilus. GAD immunoreactive neurons, although sparse, were found in the dorsal part of the lateral geniculate nucleus. In addition, puncta and fibers immunoreactive for GAD were also observed in this same nucleus. These results in Caiman utilizing GAD are similar to observations on the dorsal part of the lateral geniculate nucleus of other reptiles in which antisera to gamma amino butyric acid (GABA) were used. PMID- 8193927 TI - Effects of kainic acid microinfusions on hippocampal type 2 RSA (theta). AB - This study investigated the effects of bilateral, selective lesions of subfield CA3, produced by intrahippocampal administration of kainic acid, on the generation of hippocampal type 2 RSA. Within 4 weeks of lesioning, animals were anesthetized with urethane and microelectrode depth profiles were performed throughout the dorsal-ventral extent of the hippocampus. In control animals, spontaneous and stimulation-induced RSA was present at the amplitude maxima in stratum oriens of the CA1 and at the level of the hippocampal fissure. Animals that received intrahippocampal microinfusions of kainic acid showed a significant reduction of RSA amplitude at both the stratum oriens and fissure regions. These results suggest that the CA3 subfield may play an important role in the production of type 2 RSA. PMID- 8193928 TI - Restraint stress suppresses experimental allergic encephalomyelitis in Lewis rats. AB - We studied the effect of restraint stress on experimental allergic encephalomyelitis (EAE), a model for the human disease multiple sclerosis (MS), in Lewis rats. Rats were subjected to 12 h restraint stress for 3 consecutive nights from the first (day 1) or the eighth day (day 8) after sensitization with the antigen (guinea-pig spinal cord). All controlled rats exhibited clinical and histologic signs of EAE. The mean +/- SD of incubation time, clinical score (0-4) and histologic score (0-3) for this group were 12.8 +/- 1.0 days, 2.7 +/- 0.6, and 2.3 +/- 0.7, respectively. Restraint stress from day 8 significantly suppressed EAE: the mean +/- SD of incubation time, clinical score, and histologic score for this group were 17.2 +/- 2.2 days (p < 0.001), 1.8 +/- 1.3 (p < 0.05), and 1.5 +/- 0.9 (p < 0.02), respectively. Restraint stress from day 1 did not modify EAE. The findings suggest that stressful factors may exert an influence on the clinical course of MS. PMID- 8193929 TI - Subthalamic nucleus and globus pallidus lesions alter activity in nigrothalamic neurons in rats. AB - Lesions of the subthalamic nucleus or the globus pallidus altered the response of substantia nigra pars reticulata neurons (antidromically identified as projecting to the thalamus) to electrical stimulation of the frontal agranular cortex. In intact animals, cortical stimulation evokes three independent responses (excitation, inhibition, excitation) that may occur singly or in various combinations. The independence of the various responses, especially the temporally coincident excitatory and inhibitory responses, suggests that the net inhibitory and excitatory pathways carrying these signals from the cortex may converge to varying degrees on individual nigrothalamic neurons. Subthalamic lesions increased total response duration (from 28.4 to 39.7 ms), increased the duration of inhibition (from 18 to 30 ms), decreased the occurrence of excitatory responses, and decreased the intensity of the second excitation (from 1.1 to 0.6 spikes/s). Lesion of the globus pallidus also increased total response duration (up to 38 ms), but by increasing the duration of the second excitation (from 15.1 up to 23.8 ms). The intensity of the second excitation (from 1.1 to 1.5 spikes/stimulus) and the number of cells showing the first and second excitations also increased. The incidence, but not the duration, of the inhibition increased. The mean firing rate increased after subthalamic nucleus lesion (34.2 spikes/s) as compared to intact (27.0) or globus pallidus lesion (25.6). These changes may reflect changes in the relative contribution of the five different pathways transmitting information from the cortex to the substantia nigra. In all cases the cortico-striato-nigral pathway is largely intact.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193930 TI - Different effects of unilateral and bilateral lesions of the dorsal raphe nucleus on puberty and first ovulation. AB - The effects of unilateral and bilateral electrolytic lesions of the dorsal raphe nuclei (DRN) of 30-day-old rats, on the spontaneous and induced ovulation, were analyzed. The bilateral lesion and the lesion on the right side of the DRN delayed the age of first vaginal estrous. None of the animals with bilateral lesion on the DRN ovulated on the day of first estrous (0/8 vs. 12/15, p < 0.05). The ovulation rate in animals with unilateral lesion on the DRN was similar to sham-operated animals, but the number of ova shed by ovulating animals increased in the ovary ipsilateral to the lesion (lesion on right DRN, right ovary: 6.5 +/- 0.5 vs. 4.5 +/- 0.4; lesion on left DRN, left ovary: 6.4 +/- 0.3 vs. 4.2 +/- 0.4, p < 0.05). By the injection of human chorionic gonadotropin, ovulation was restored in rats with a bilateral lesion on the DRN (3/5 vs. 0/8, p < 0.05). The present results suggest that serotoninergic input to the hypothalamus, arising from the DRN, exerts a facilitatory influences on the control of luteinizing hormone release. To explain the increase in the number of ova shed by the left and right ovary, observed in rats with an ipsilateral lesion, we suggest the existence of a neural connection between the DRN and the ovary. PMID- 8193931 TI - Early and persistent abnormalities in rats with neonatally acquired Borna disease virus infection. AB - Newborn rats inoculated with Borna disease virus (BDV) develop a persistent, tolerant nervous system infection (PTI-NB), with no signs of encephalitis or Borna disease. We measured body weight, body length, taste preferences, and spontaneous locomotor activity over a 4-month period in PTI-NB and control rats. PTI-NB rats had decreased weight and length but not detectable disturbances in growth hormone and insulin-like growth factor-1 biosynthesis as compared to control rats. In single bottle taste acceptance tests, PTI-NB rats did not differ from controls and drank normal amounts of all solutions. When offered a choice of solutions in two-bottle taste preference tests, PTI-NB rats exhibited a normal preference for saccharin and a normal aversion for quinine, but an exaggerated preference for saline. At 1 and 4 months of age, PTI-NB rats were significantly more active than normal rats, although only 1-month-old PTI-NB rats had increased daytime activity. Thus, even in the absence of encephalitis, BDV infection of the PTI-NB rat is associated with a number of physiological and behavioral abnormalities. PMID- 8193932 TI - Ventromedial hypothalamus mediates stress-induced hypocalcemia via the gastric vagus in rats. AB - A hypothalamo-vagal mechanism of immobilization (IMB) stress-induced hypocalcemia was investigated in rats. Bilateral lesions in the ventromedial nucleus of the hypothalamus (VMH), but not those of the lateral hypothalamic area (LHA) or the paraventricular nucleus (PVN), eliminated the calcium-lowering effect of IMB. None of these lesions, however, affected the basal levels of the blood calcium. An electrical stimulation of the VMH induced a significant decrease in the blood calcium level (0.07 mM fall) 60 min after stimulation. The hypocalcemic response was eliminated by a vagotomy of the gastric branches but not by that of the thyroid/parathyroid branches. These results suggest that the VMH mediates IMB induced hypocalcemia through its influence on the gastric vagus. PMID- 8193933 TI - Vomeronasal organ-mediated induction of fos in the central accessory olfactory pathways in repetitively mated female rats. AB - Removal of the VNO significantly reduced the enhancement of lordosis and the induction of fos immunoreactivity in luteinizing hormone-releasing hormone (LHRH) neurons in ovariectomized estrogen-primed rats. There was a significant positive correlation between the two variables. In the accessory olfactory bulb (AOB) of the repetitively mated rats, the number of fos-positive cells in the granule (G) cell layer was significantly lower in the VNO-removed rats, whereas that in the mitral (M) cell layer was not significantly different between VNO-removed and VNO sham females. The G/M ratio (calculated by dividing the mean number of fos positive cells in the G cell layer by that in the M cell layer), taken as an estimate of the output of the AOB, was relatively larger in the VN-sham as compared with the VNO-removed rats. There were significant positive correlations between G/M ratio and the increase in LQ and between the G/M ratio and the percentage of fos-positive LHRH cells. The positive correlation between the number of fos-positive cells in the posterodorsal medial amygdala (PDMA) and the increase in LQ and that between the number of fos-positive cells in the PDMA and the percentage of fos-positive LHRH cells were significant, supporting the role of the medial nucleus of amygdala in lordosis. However, the correlation between G/M ratio and the number of fos-positive cells in the PDMA was not significant, indicating that fos immunoreactivity in the PDMA is not directly related to that in the AOB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193934 TI - Expression of c-fos-like protein in the rat brain after injection of interleukin 1-beta into the gingiva. AB - Expression of the c-fos proto-oncogene in the rat brain was examined by immunostaining for fos, the nuclear protein product of the c-fos gene, after injection of interleukin-1-beta (IL-1 beta) into the gingiva of an incisor. The distribution pattern of labelled cells was compared with that induced by tooth pulp stimulation. Neurons that express fos-immunoreactivity (fos-IR) appeared in several regions in the neuraxis 1.5 h after IL-1 beta injection, peaked at 2 h, and then declined. Labelled cells were found bilaterally in regions that contribute to pain-relay and pain-inhibition. The distribution of labelled cells almost matched the pattern induced by noxious tooth pulp stimulation. In indomethacin-pretreated animals, no neurons expressing fos-IR were found in nuclei associated with relay of nociception nor in nuclei contributing to inhibition of nociception. The results suggest that a small amount of IL-1 beta at the site of periodontal disease can induce fos-IR in brain neurons through increased prostaglandin production. PMID- 8193935 TI - Chloride channel block phase advances the single-unit activity rhythm in the SCN. AB - The mammalian suprachiasmatic nuclei (SCN) contain a circadian pacemaker that exhibits a 24 h rhythm in single-unit activity in vivo and in vitro. Chloride channel block by a saturating concentration of picrotoxin at either CT6 or CT15 produces large phase advances in the SCN single-unit activity rhythm in vitro. These phase advances are not affected by simultaneous blockade of voltage sensitive sodium and calcium channels by TTX and magnesium. Thus, the effects of picrotoxin appear to be mediated by direct blockade of the chloride channel, rather than subsequent membrane depolarization. GABA-A receptor-mediated chloride flux may be part of the mechanism of circadian timekeeping. PMID- 8193936 TI - Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain. AB - We and others have reported that c-fos protein is induced in the hypothalamus and brain stem of the rat following central and peripheral injections of endotoxin (lipopolysaccharide; LPS). We have now examined possible mechanisms through which LPS induces c-fos protein. The cyclooxygenase inhibitor indomethacin and the glutamate NMDA antagonist MK801 inhibited c-fos protein in the paraventricular nucleus (PVN), supraoptic nucleus (SON), and the A1/A2 regions of the brain stem induced by IP or IV injections of LPS (40 micrograms). The H1 histamine antagonist diphenhydramine, but not the H2 histamine antagonist cimetidine, reduced the amount of c-fos labeling. MK801 also attenuated the effects of stress (foot shock) on c-fos protein; however, indomethacin had no effect on c-fos protein induced by stress. We next examined the importance of visceral afferent innervation on the response to LPS or stress. Subdiaphragmatic vagotomy completely blocked the induction of c-fos protein following IP injections of LPS; however, vagotomy had a minimal effect on c-fos protein induced in the PVN and SON following IV injections of LPS, but potentiated c-fos induction following foot shock. Thus, prostaglandin synthesis, glutamate release, histamine receptors, and visceral afferents represent functional biochemical and neural pathways through which endotoxin activates c-fos protein in specific autonomic and neuroendocrine regulatory nuclei. Activation of NMDA glutamate receptors may represent a final common pathway for the induction of c-fos protein in the brain induced by both endotoxin and stress. PMID- 8193937 TI - Cellular forms and functions of brain microglia. AB - Consistent with the recent characterization of microglial cells as macrophages, an overall picture for the unique function of these cells in CNS tissue has developed. The microglia are derived from blood monocytes that migrate into the tissue during fetal development and subsequently remain after complete formation of the blood-brain barrier. These monocytes give rise to the ramified microglia of adult tissue through the developmental intermediate of amoeboid microglia. Ramified microglia appear uniquely adapted in contrast to other tissue macrophages based on their stability or lack of turnover and mitotic capability. The ramified cells, while usually downregulated, can convert into active macrophages termed reactive microglia; this conversion appears to occur nonspecifically in response to any injury. Further, reactive microglial cells can fuse to form giant multinucleated cells during viral infections. Each microglia cell form possesses a characteristic morphology and differing functional state with regard to macrophage activity. In their role as tissue macrophages, microglia are involved in immune responses, tissue transplantation, and AIDS dementia complex, as well as many other neurological mechanisms and diseases. PMID- 8193938 TI - [Treatment of heroin addicts by substitution with methadone. Importance, limits and experience in France]. AB - The authors present a review of literature and their personal experience concerning the practice of methadone substitutive therapy for heroin addicts in France. In their experience, the use of methadone, within the frame of a controlled administration and in the perspective of a specific pharmaco therapeutic profile, is a valuable therapeutical option. Otherwise, methadone could only induce a new and further pharmacological dependence. The use of methadone has often been the subject of controversies overlooking the clinical reality of drug addiction. Therefore, a controlled use of methadone remains a valuable therapeutic tool if its indications are strictly delimited. PMID- 8193939 TI - [Partial surgery of epitheliomas at the level of the glottis. An update]. AB - Seven hundred and thirty three patients with glottic squamous cell carcinoma were treated with partial laryngeal surgery at our institution over a sixteen years period of time. Three hundred and ninety four patients were operated from 1972 through 1980 and three hundred and thirty three from 1980 through 1988. This retrospective study analyse local failure according to the surgical technique performed. Surgical technique was either a thyrotomy, a vertical partial laryngectomy or a supracricoid laryngectomy with cricohyoidoepiglottopexy. Among the 394 patients treated from 1972 through 1980, local failure was reported according to the T stage, the precise tumor location within each stage, the true vocal cord mobility and the surgical procedures. There was a diverse group of lesions within each T stage that responded differently to the surgical approaches. The differences in the local recurrence rates are discussed in terms of careful preoperative assessment and choice of surgical technique. This study support the premise that the choice of the surgical technique requires accurate preoperative assessment of tumor extend and laryngeal mobilities. PMID- 8193940 TI - [Drug addiction and AIDS]. PMID- 8193941 TI - [Importance of bacterial vaccines]. AB - The vaccines presently developed in laboratories are more numerous than the ones in current use. This acceleration of research efforts was made possible by a genuine biotechnological revolution which opened new avenues for vaccine preparation, with techniques such as the selection of relevant antigens and the use of subunit vaccines. Genetic engineering plays an increasing part in the development and production of both live and inactivated vaccines. PMID- 8193942 TI - [Haemophilus influenzae vaccines]. AB - The haemophilus vaccines are made of the type b capsular polysaccharide of haemophilus influenzae, polyribosylribitol phosphate (PRP), which is responsive of pathogenic power. However the responsiveness of children to PRP vaccine was found to be very poor in infants. The concept of conjugating carbohydrate with a carrier protein increasing immunogenicity of the PRP led to 4 PRP--protein conjugate vaccines: PRP-diphtheria toxoid conjugated vaccine (PRP-D), outer membrane protein of Neisseria meningitidis conjugated (PRP-OMP), cross-reacting mutant diphtheria protein (PRP-HbOC) and tetanus-Toxoid conjugated vaccine (PRP T). The antibody response to PRP is enhanced and a good booster response is obtained in infants as soon as two months of age. However the 4 vaccines differ markedly in ability to stimulate antibody production. PRP-D is less immunogenic and must be given in children older than 12 months. Antibodies are significantly higher after 3 injections of PRP-T or PRC-HbOC than PRP-OMP. Only PRP-OMP produces a clinically pertinent elevation of antibodies after 2 injections. The coadministration of PRP-OMP, PRP HbOC, PRP-T with diphtheria-tetanus-pertussis vaccines does not alter the antibody PRP response. The polio antibodies are lower if injectable polio vaccine is mixed with PRP-OMP, but the level is the same with PRP-T vaccine. The others antibodies (D, T, Coq), are at same levels. The field trials have shown a high efficacy of all those 4 vaccines. However PRP-D vaccine gave less good result in infants before 6 months. The safety of these vaccines is good and not altered by combination with investigation by diphtheria-tetanus pertussis vaccines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193944 TI - [Vaccination against the enterobacteriaceae responsible for enteric infections]. AB - Development of vaccines against enterobacterial species responsible for enteric infections sounds like an unrealistic project. On the other hand, based on our growing understanding of the pathogenesis of infections caused by the major species (i.e. Salmonella typhi, Shigella flexneri and Shigella dysenteriae 1, Enterotoxigenic Escherichia coli) and on our better characterization of the immunological parameters of mucosal protection, it is likely that a limited number of vaccines controlling diseases such as typhoid fever, bacillary dysentery and cholera-like E. coli infections will become available. There are three major problems that still need to be solved: the variety of antigens and antigenic specificities, the nature of protective antigens and, provided that these prerequisites are fulfilled, the presentation of the vaccine and the immunization route. With the exception of typhoid fever, which has a systemic phase that probably makes immunization attempts by purified Vi antigen successful, experimental strategies rely very much on induction of a mucosal immunity. Either subunit vaccines, or genetically manipulated strains which attenuated virulence are currently considered. PMID- 8193943 TI - [Pneumococcal vaccination. Assessment and prospects]. AB - Licensed in 1977, the pneumococcal vaccine is sparsely used in France. By contrast most recent epidemiological studies demonstrated that this vaccine is capable to significantly lower the incidence of pneumococcal pneumonia in groups in which this infection is frequently life-threatening. The efficacity of such immunisation is high unless subject are immunocompromised. Recommendations for immunisation practices should be based these data and durely enforced. PMID- 8193945 TI - [New antibacterial vaccines]. PMID- 8193946 TI - [Inter- and intra-cephalic variations in pathogenicity in Toxoplasma gondii. Clinical and epidemiologic consequences]. AB - Clinical and epidemiological studies, especially the ones conducted in HIV+ patients indicate that the pathogenicity of Toxoplasma gondii varies according to the strain considered. The differences observed among strains are represented by distinct genomic DNA patterns which could be experimentally evaluated by means of the RFLP (Restriction Fragment Length Polymorphism) and the RAPD (Random Amplified Polymorphic DNA). If on the one hand virulent strains present very similar genomic DNA patterns, on the other hand chronic strains are highly polymorphic. These differences may be, at least in part, due to the asexual (clonal) multiplication of virulent strains. The existence of an intraspecific pathogenicity variation and genetic heterogeneity was observed within a single strain either after attenuation (infection in Fischer or Wistar rats), or during reactivation (in immunodepressed animals). In a congenital model of toxoplasmosis, the differences are detected from one animal to another and sometimes, even from one organ to another in the same host. This finding do not seem to be related to the occurrence of mutations but rather to selective pressures, notably of immunological origin, exerted by the infected organism. A better understanding of these phenomena could result in significant therapeutic and prophylactic advances. Our first effort will be directed to the establishment of more precise diagnostic and predictive elements. The accomplishment of this step relies on the use of primers deriving from DNA sequences characteristic of virulence and which will be tested by PCR. PMID- 8193947 TI - [Childhood autism: a relating deficiency due to a developmental disorder of the central nervous system]. AB - Childhood autism with its difficulties in relating to others has been for a long time imputed to conscious or unconscious educative errors of the mother. Clinical and biological data can be opposed to this conception. Familial movies analysis exhibits early disorders in attention, perception, intention, limitation and muscular tone. Later, recording of cerebral reactivity to auditory stimulations confirms deficiencies in attention, perception, association ... and shows a diminution of the responses in the left hemisphere. Abnormalities in the development of the cerebellum are also described. Modifications of main neurotransmitters as Dopamine and Serotonin and their derivatives are often present. A recent study of the genes which control enzymes regulating metabolism of these transmitters does not show evident modifications by polymorphism analysis. On the contrary a peculiarity in the Harvey-RAS gene allows to differentiate in a significant way an autistic and a normal group. This gene is involved in the regulation of growth factor and/or differentiation of neural cells. These observations support the hypothesis considering autism as a relating deficiency due to a developmental disorder of central nervous system. PMID- 8193948 TI - [Fibrinogen, a vascular risk factor]. AB - Epidemiological studies have consistently correlated plasma fibrinogen level to the risk of coronary heart disease (CHD) and acute ischemic stroke. Several mechanisms have been proposed such as the role of fibrinogen in the viscosity of blood, the participation of fibrinogen in both fibrin clot formation and platelet aggregation. However, there is no evidence that the increase in fibrinogen is directly responsible for the vascular disease since the cytokines which participate to the synthesis of fibrinogen by the hepatocytes, such as interleukin 6, could also induce an endothelial cell damage by increasing tumor necrotic factor (TNF) production. In these conditions fibrinogen increase could therefore only represent a marker of cytokine production which in turn is responsible for vascular injury. In addition, for the pathogenesis of atherosclerosis, the influence of fibrinogen is not only mediated by way of increased fibrinogen concentration but could be due to a structurally variant fibrinogen. The recent epidemiological studies have shown that the variation at the beta locus of fibrinogen is associated with an increase risk of peripheral atherosclerosis. The finding concerning dysfibrinogenemia and thrombosis (Dusart and Tampere) create further opportunities to enrich knowledge of the link between the association of abnormal gel structure and thrombotic diseases such as myocardial infarction or stroke at young age. This abnormal clot structure could contribute to thrombogenicity by decreasing the capacity of these clots to be degraded by fibrinolytic enzymes or by decreasing thrombin binding since fibrin is considered as a "thrombin trap".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193949 TI - [Does aesthetic surgery form part of mainstream surgery or is it an entirely separate sector? Reflections and proposals for better protection of the public]. AB - In contempt of the laws and regulations in force, several thousand unqualified practitioners carry out aesthetic surgery although only a mere few hundred are legally entitled to practice this surgical specialty. We are aware, in the present system which has no efficient control systems, that the public is no longer able to identify this small group of charlatans and incompetents. We call on massive concerted effort by the responsible public authorities to ensure that the general public receives the necessary protection. Amongst others, we demand that: The ministry of health, integrates all medical products and medical devices aimed at the aesthetic sector into the list of medical products and medical devices to marketing authorization (authorization de mise sur le marche--AMM) or to endorsement in compliance with the Huriet Law of 10.12.1988. The conseil national de l'ordre des medecins, (national council of doctors advisory board), ensures that the laws and regulations in force governing the value of diplomas, qualifications and competences are respected, be aware of the obsolescence of the general nature of the medical degree, inapplicable due to the efficiency and thus the dangerous nature of modern medicine. The ministry of justice, clearly defines the nature of the informed consent demanded from the patient prior to any therapeutic treatment, ensures the conditions required for legitimate compensation for prejudices caused by therapeutic risks, specifies the doctor's responsibility without malpractice conditions, be aware of the perverse effects caused by the abandonment of the obligation of means and its replacement by an obligation of results demanded from the doctor, to correct the unjust and anomalous situation which opposes the ten year responsibility of the medical product or medical devices manufacturer with the thirty year responsibility of the doctor using these products or equipment. PMID- 8193950 TI - ODEN: a program package for molecular evolutionary analysis and database search of DNA and amino acid sequences. PMID- 8193951 TI - Improved sensitivity of profile searches through the use of sequence weights and gap excision. AB - Position-specific substitution matrices, known as profiles, derived from multiple sequence alignments are currently used to search sequence databases for distantly related members of protein families. The performance of the database searches is enhanced by using (i) a sequence weighting scheme which assigns higher weights to more distantly related sequences based on branch lengths derived from phylogenetic trees, (ii) exclusion of positions with mainly padding characters at sites of insertions or deletions and (iii) the BLOSUM62 residue comparison matrix. A natural consequence of these modifications is an improvement in the alignment of new sequences to the profiles. However, the accuracy of the alignments can be further increased by employing a similarity residue comparison matrix. These developments are implemented in a program called PROFILEWEIGHT which runs on Unix and Vax computers. The only input required by the program is the multiple sequence alignment. The output from PROFILEWEIGHT is a profile designed to be used by existing searching and alignment programs. Test results from database searches with four different families of proteins show the improved sensitivity of the weighted profiles. PMID- 8193952 TI - ADVANCE and ADAM: two algorithms for the analysis of global similarity between homologous informational sequences. AB - Two algorithms for the analysis of global similarity between sequences of informational polymeric molecules (nucleic acids and proteins) are proposed: one (ADVANCE) merely gives a quantification of the global similarity between two sequences, and is very fast; the other (ADAM) also provides an alignment of the sequences. Both are new algorithms, implement Sellers' theorem, do not require parameters, are able to analyze two sequences of 32,000 elements each, and are fast; nevertheless, they differ deeply in the algorithm, in the programming language type, and in their planning, and will thus have to be treated separately. In fact, the different nature of the required output in each program causes the common aim (to obtain power and speed) to be reached only through very different ways and methods. PMID- 8193953 TI - Hierarchical Access System for Sequence Libraries in Europe (HASSLE): a tool to access sequence databases remotely. AB - Sequence databases in biology are growing exponentially. Not only are large sites needed to keep the data, but the number of customers is continuously increasing. Network access plays a key role in utilizing remote resources. However, both synchronous and asynchronous access require tools that are currently non-standard in molecular biology computing. Additionally, information discovery of today frequently focuses on centers rather a hierarchically interconnected facilities. HASSLE (Hierarchical Access System for Sequence Libraries in Europe) is an implementation of an application-independent, user-transparent access tool in molecular biology. It features tools for both clients and information providers to permit accounting and/or prioritization on various levels. HASSLE focuses on the network aspect of the molecular biology computing and assumes that it is possible to have database applications available as remote 'services' (programs, program packages or utilities) which can be started by a simple command script after a suitable feed of datafiles. The current system provides these services for searching with programs like FASTA or BLAST which are compiled as obtained from vendors or servers. PMID- 8193954 TI - Simplified user poll and experience report language (SUPER): implementation and application. AB - Biological computing is generally organized as standalone implementation on a PC type computer or on a central facility (e.g. a university computer center). Services provided by central facilities need to be tailored to the user community. Unless very work-intensive individual contacts are used, the feedback must be collected with generalized tools, such as questionnaires distributed in the form of a newsletter. We have developed a method to have such polls automated and tailored, as well as having multiple-choice questions combined with branching after fundamental questions. As the evaluation of the results needs to know the questions asked, we have also included a method to process the answers and give detailed tables on the answers. SUPER was applied in a poll to query the academic usership in Switzerland on the usage of molecular biology databases. PMID- 8193955 TI - fastDNAmL: a tool for construction of phylogenetic trees of DNA sequences using maximum likelihood. AB - We have developed a new tool, called fastDNAml, for constructing phylogenetic trees from DNA sequences. The program can be run on a wide variety of computers ranging from Unix workstations to massively parallel systems, and is available from the Ribosomal Database Project (RDP) by anonymous FTP. Our program uses a maximum likelihood approach and is based on version 3.3 of Felsenstein's dnaml program. Several enhancements, including algorithmic changes, significantly improve performance and reduce memory usage, making it feasible to construct even very large trees. Trees containing 40-100 taxa have been easily generated, and phylogenetic estimates are possible even when hundreds of sequences exist. We are currently using the tool to construct a phylogenetic tree based on 473 small subunit rRNA sequences from prokaryotes. PMID- 8193956 TI - PHD--an automatic mail server for protein secondary structure prediction. AB - By the middle of 1993, > 30,000 protein sequences has been listed. For 1000 of these, the three-dimensional (tertiary) structure has been experimentally solved. Another 7000 can be modelled by homology. For the remaining 21,000 sequences, secondary structure prediction provides a rough estimate of structural features. Predictions in three states range between 35% (random) and 88% (homology modelling) overall accuracy. Using information about evolutionary conservation as contained in multiple sequence alignments, the secondary structure of 4700 protein sequences was predicted by the automatic e-mail server PHD. For proteins with at least one known homologue, the method has an expected overall three-state accuracy of 71.4% for proteins with at least one known homologue (evaluated on 126 unique protein chains). PMID- 8193957 TI - DNA modeller: an interactive program for modelling stacks of DNA base pairs on a microcomputer. AB - DNA Modeller is a microcomputer program for interactively manipulating up to 20 bp in a DNA double helical arrangement. It calculates the van der Waals and electrostatic energies of base-base interactions using the AMBER potential, minimizes the energy with respect to the pair (buckle, propeller, opening, shear, stretch, stagger) and step (tilt, roll, twist, shift, slide, rise) parameters, calculates lengths of the canonical hydrogen bonds between the complementary bases, and calculates interatomic distances between the successive base pairs. Input/output files are simple lists of the step and pair parameters or lists of the atom specifications (N1, C2, etc.) and their Cartesian coordinates (compatible with the Desktop Molecular Modeller*.mol files). The program is supplied with a readbrk utility which transforms PDB/NDB to the *.mol format readable by DNA Modeller. The DNA crystal structures deposited in the PDB or NDB databases can thus be analyzed, and their bases visualized and interactively manipulated. In addition, DNA Modeller can calculate the base pair and step geometrical parameters and interaction energies. A plotter utility creates wire mono or stereo pictures of the bases. This program is designed for IBM-compatible computers working under DOS or can run as a DOS application under MS Windows 3.x or Merge (SCO Unix DOS emulator). PMID- 8193958 TI - Some features on RNA folding structures of cytochrome c oxidase subunit II and cytochrome P450. AB - We have defined the folding index of the RNA secondary structure and compared the value of this index obtained from a given RNA molecule with one from the random sequences with the same A, U, G, C ratio. The mRNA of the cytochrome c oxidase subunit II and cytochrome P450 from various species was analyzed. We found that the mRNA of these genes were more folded than the random sequences and the coding regions of these mRNA were as equally folded as the random sequences. This result suggests that the coding region of these mRNA has no more important secondary structure than have the random sequences with the same A, U, G, C ratio. PMID- 8193959 TI - Integrated software for probabilistic identification of microorganisms. AB - A computer program has been designed to carry out microbial identification using probability matrices along with the Bayes theorem. When implementing the system the main considerations have been flexibility, user-friendliness and integration of identification coefficients and mathematical tests of matrices. The program has been developed in QuickBASIC for PC/MS-DOS operating systems and presents a menu-driven structure that aims to facilitate its use. PMID- 8193960 TI - De novo design of peptides and proteins: machine-generated sequences by the PROSA program. PMID- 8193961 TI - Fast protein block searches. AB - Profile searches using aligned short protein blocks are an effective method for identifying putative protein functions. An algorithm is presented that accelerates block searches by a factor 2-5 with only limited lack of sensitivity; this algorithm is particularly suited for application in large-scale genome research. PMID- 8193962 TI - Radiologic research: a cornucopia. PMID- 8193963 TI - Magnetic field strength issues in magnetic resonance imaging. AB - The authors review the current status of magnetic resonance imaging (MRI) with respect to magnetic field strength. The discussion covers the practical aspects of MRI--safety, throughput and costs--as well as the clinical aspects as they are influenced by field strength. Data on the world distribution of MRI units of various field strengths are presented. Canada had the highest proportion of high field units among the 11 countries or regions included in this comparison, probably because most Canadian MRI units are located in teaching hospitals, where they are used for both research and clinical work. PMID- 8193964 TI - Ovarian cancer: computed tomography findings. AB - Ovarian cancer is one of the most common malignant lesions in women. Radiologists are often called upon to interpret and report computed tomography (CT) findings for staging such lesions and for evaluating the patients' response to therapy. A variety of manifestations of this disease can be seen with CT, each of which can have a spectrum of appearances. These manifestations include ascites, peritoneal seeding, and visceral and nodal metastasis. A selection of situations commonly encountered in women with ovarian cancer, as well as several unusual ones, are depicted in this pictorial essay. PMID- 8193965 TI - Schizencephaly: antenatal and postnatal assessment with colour-flow Doppler imaging. AB - Schizencephaly, a disorder of neuronal migration, is rarely discovered in utero. Three cases, detected in utero and followed through the early neonatal period, were assessed with colour-flow Doppler imaging in an attempt to determine whether the clefts were associated with any demonstrable vascular disturbance. The Doppler spectral wave-forms of the fetal and neonatal internal carotid and middle cerebral arteries were normal in two of the cases, whereas the right middle cerebral artery was persistently occluded in the third. Although Doppler imaging was not performed during the first trimester (when the defect occurs), these findings suggest that a vascular lesion, such as occlusion of the middle cerebral artery with or without complete recanalization, may result in the clefts seen in patients with schizencephaly. Two of the fetuses had been exposed to cocaine in the first trimester, and an association between cocaine-induced vasospasm and schizencephaly is suggested. PMID- 8193966 TI - Colour-flow Doppler artifacts in anechoic soft-tissue masses of infants. AB - Colour-flow Doppler imaging is a noninvasive, readily accessible method of assessing the vascularity of soft-tissue masses. To produce acceptable images of flowing blood, various types of signal processing are needed to suppress the colour in moving but nonvascular masses. The author describes two infants with anechoic soft-tissue masses; both masses demonstrated colour flow. One patient had a vascular hemangioma, in which the colour was due to blood flow; the other had a nonvascular lymphangioma, in which the colour was caused by persistent movement between the transducer and the leg being scanned. Artifacts such as that observed in the lymphangioma may be misinterpreted as flow, unless Doppler spectral analysis is employed. Differentiation between vascular and nonvascular soft-tissue masses before surgical excision is important. PMID- 8193967 TI - Peroral pneumoileum in patients with ileostomy. AB - Peroral pneumoileum extends the peroral pneumocolon technique to patients with ileostomy to improve visualization of the ileum when the small-bowel examination is limited by poor distension, overlapping loops or adhesions. The author describes the technique in detail and presents the findings for 25 patients (10 men and 15 women) examined for suspected ileostomy dysfunction, recurrent Crohn's disease or ileal obstruction remote from the stoma. In only one patient was retrograde single-contrast enema required in addition to the antegrade small bowel series with peroral pneumoileum. In seven of the patients, the demonstration of abnormalities with this technique influenced subsequent management. Peroral pneumoileum overcomes several of the limitations of antegrade and retrograde examinations and enables complete jejunoileal assessment with a single radiologic procedure. PMID- 8193968 TI - Reduction of bowel motion artifact during digital subtraction angiography: a comparison of hyoscine butylbromide and glucagon. AB - The authors compared the effectiveness of hyoscine butylbromide (Buscopan) and glucagon in reducing bowel motion artifact during abdominal intra-arterial digital subtraction angiography. Sixty-six patients referred to the radiology department of a tertiary-care hospital for abdominal angiography between October 1989 and July 1992 consented to participate in the study. Diabetic patients receiving insulin and those with glaucoma were not considered for the study. The patients were assigned at random to receive either Buscopan (39 patients) or glucagon (27) intravenously before angiography. Images obtained at three stages during the procedure were reviewed independently by three experienced vascular radiologists who were blinded as to treatment group; images for nine patients in the Buscopan group and seven in the glucagon group were excluded because of breathing artifact or body movement. For each image the radiologists scored bowel motion in each section of a six-section grid. The bowel motion scores during early, middle and late arterial phases and the total scores for the two groups did not differ significantly (t-test). On the basis of these findings, the authors continue to use Buscopan because it is less expensive than glucagon. PMID- 8193969 TI - [A retrospective study of 93 cases of orbital and eye tumors using tomodensitometry]. AB - The purpose of this study was to review certain computed tomography (CT) criteria in relation to the histopathologic diagnosis of orbital tumours. One hundred and forty cases of orbital tumour were evaluated by CT between 1979 and 1992 at two tertiary-care hospitals. The radiologic material was available and the histopathologic diagnosis had been clearly established for only 93 of these; these cases were reviewed in detail for the study. The radiologic semiology of the cases was compared with the pathological diagnosis. The characteristics evaluated were tumour localization, attenuation, contrast enhancement, the presence of calcifications, the morphologic features and changes in the neighbouring bony structures. The authors present here the findings for the most commonly encountered tumours: uveal melanoma (observed in 50 cases), lymphoma (in 8), optic glioma (in 6), meningioma (in 6), dermoid cyst (in 5) and metastasis (in 5). Using the current literature for corroboration, the authors suggest an approach to diagnosis on the basis of the CT criteria discussed. PMID- 8193970 TI - Findings of magnetic resonance and colour-flow Doppler imaging of orbital embryonal rhabdomyosarcoma. AB - The authors describe a case of embryonal rhabdomyosarcoma of the orbit evaluated with magnetic resonance imaging (MRI) and colour-flow Doppler imaging. MRI demonstrated a markedly enhancing tumour with no discrete vessels. Colour-flow Doppler ultrasonography showed evidence of perfusion; however, discrete vascular channels were difficult to visualize, and no evidence of large vessels within the tumour was found at surgery. The differential diagnosis of this condition is discussed, as well as the potential role of colour-flow Doppler imaging in the assessment of orbital tumours, a role in which this method has not yet been widely applied. PMID- 8193971 TI - Multiple chorioangiomas: ultrasonographic appearance, diagnosis and significance. AB - Multiple chorioangiomas of the placenta are extremely rare. The authors report one such case diagnosed by ultrasonography. The importance of the diagnosis, possible fetomaternal complications and management of this condition are discussed. PMID- 8193972 TI - Internal abdominal hernia: diagnosis with ultrasonography. AB - The imaging findings associated with internal abdominal hernia have been reported for plain radiography, barium studies, arteriography and computed tomography. The authors present a case in which the ultrasonographic findings indicated left paraduodenal hernia. In the investigation of an abdominal mass, the presence of changing cystic or tubular internal components and a surrounding membrane should arouse suspicion of an internal hernia. PMID- 8193973 TI - Primary carcinoma of the gallbladder: atypical presentation with gangrenous cholecystitis. AB - Primary carcinoma of the gallbladder developing in patients with longstanding ulcerative colitis is a rare but recognized complication. The authors describe a 45-year-old patient who presented with gangrenous cholecystitis, which was detected by ultrasonography. PMID- 8193974 TI - Perforated jejunal diverticulosis: radiologic diagnosis. AB - Jejunoileal diverticulosis, which is usually asymptomatic, is commonly found at autopsy or during small-bowel barium examination. Perforation of diverticula can cause generalized or localized intra-abdominal inflammatory disease, depending to some extent on the site of the perforation. The authors describe a patient with perforation of a jejunal diverticulum; the condition mimicked colonic inflammatory disease clinically and ultrasonographically. The correct diagnosis was made on the basis of the findings of cross-sectional imaging and barium examination. PMID- 8193975 TI - Direct sampling of the cavernous sinus in Cushing's disease. AB - Sampling of the petrosal sinus is a sensitive and accurate method of diagnosing Cushing's disease. Sampling of the inferior petrosal sinus has been performed with a steam-shaped no. 4 or 5 French soft catheter in some centres. However, a recent report described two patients who suffered major injury to the brain stem as a result such sampling. The authors describe a series of five patients who underwent simultaneous, direct sampling of the cavernous sinuses with a Tracker microcatheter (Target Therapeutics, Fremont, Calif.) for the diagnosis of Cushing's disease. No complications occurred in this small group. The authors conclude that this procedure is a safe and accurate means of diagnosing Cushing's disease; the technique is also helpful in locating adrenocorticotropin-producing microadenoma. PMID- 8193976 TI - Residents' corner. Answer to case of the month #25. Mucocele of the frontal sinus. PMID- 8193977 TI - The use of tobacco and betel quid ('pan') among Bangladeshi women in West Yorkshire. AB - The high prevalence of oral cancer in South Asia has been linked to tobacco use particularly in conjunction with chewing betel quid or 'pan'. However, it is not known whether and to what extent these habits are practised by Asian people in the United Kingdom. Home based interviews using semi-structured questionnaires were undertaken among 296 first generation Bangladeshi women resident in inner city Leeds and Bradford, West Yorkshire. 'Pan' was reportedly chewed by 282 (95 per cent) of the women, of whom 174 (62 per cent) added tobacco in leaf form, and 75 (27 per cent) as a component of zarda. Those who consumed more 'pans' daily were significantly older, less literate, had a lower educational attainment, and were more likely to believe that chewing betel quid was beneficial. Cigarette smoking was practised by 9 per cent, this group being older and having lived in the UK longer. Burnt tobacco leaves were used as an oral hygiene aid by 20 per cent. Over half (58 per cent) of the sample had never visited a dentist, the majority deeming it unnecessary. The use of tobacco and 'pan' imply an increased risk for oral cancer and precancer. Since 'pan' chewing is a traditional custom, health promotion within these communities would require a sensitive approach. Health personnel likely to be consulted by Asian groups who chew 'pan' should be aware of the danger to oral health posed by this practice. PMID- 8193978 TI - Exploring dental operators' perceptions of their clinical tasks. AB - Clinical variation is a result of the complex interaction of operator, operating environment and client variables. This study explores intra-operator characteristics by applying a technique from psychology known as Repertory Grid to New Zealand dental therapists, in order to elicit the ways in which they view their work. Individual interviews were conducted with 13 dental therapists to elicit the full range of tasks that they perform and the various ways that they describe them. Each therapist then rated her own work activities or tasks on her personal set of bipolar descriptions (personal constructs). Principal components analyses of each individual's set of ratings produced graphs which portrayed the pattern of meanings which therapists attributed to their work activities. Common features among the 13 therapists' work perceptions were then identified and categorised according to five types of variables (therapist, client, procedural, time and interpersonal). Common features included operator perceptions of painfulness of procedures, complexity of decision-making, interaction with people, stress for the therapist, preventive care for the client, routineness of task and challenge for the therapist. This detailed information gives a better understanding of the complex ways in which therapists view their tasks and therefore make decisions in the clinical setting. It could be conveniently used to develop a questionnaire to assess the empirical relationships between intra operator factors and clinical outputs. PMID- 8193979 TI - Dentists' attitudes toward auxiliaries in Malaysia. AB - A postal questionnaire survey concerning dentists' attitudes toward auxiliaries in Malaysia resulted in a 73.1 per cent response rate. The result of the study indicates that whilst the majority of the dentists agreed that dental auxiliaries usually increase productivity and permit the dentists to devote more time for more challenging tasks, a majority felt uncomfortable to be held accountable for the performance of auxiliaries. A majority of the dentists agreed that dental auxiliaries work best under direct supervision. The perceived value of the auxiliaries was more positive among public sector dentists as compared to private practitioners. Almost three-quarters of the dentists were positive towards legalising properly trained auxiliaries to work in private practice performing mainly preventive procedures. The implications of these findings relative to existing regulations, mode of practice and the future prospect in the delivery of oral health care are discussed. PMID- 8193980 TI - Subjective orthodontic treatment need and perceived dental appearance among young Finnish adults with and without previous orthodontic treatment. AB - Subjective orthodontic treatment need and perceived oral condition were studied in a sample of 226 young adult Finns with and without previous orthodontic treatment. The subjects, applicants to enter the University of Helsinki, were interviewed immediately after their entrance examination. Altogether 38.5 per cent of the subjects had received some form of orthodontic treatment. A higher percentage of subjects who had been orthodontically treated reported a current subjective need for treatment than did the untreated ones but this only reached statistical significance in men (P < 0.05). Appearance was the reason for the treatment need among 64.7 per cent of treated and among 80.0 per cent of untreated subjects. The differences in proportions were non-significant. Men were more often satisfied with their dentition than women. Most, 56.3 per cent of treated and 66.2 per cent of untreated subjects, considered their anterior teeth regularly positioned. The most prevalent type of malocclusion noted in the anterior segments was crowding (27.0 per cent), followed by malpositioned (18.6 per cent) and protruding (9.3 per cent) teeth. It is likely that those who had received orthodontic treatment, had initially had more, and more severe malocclusions than those who were untreated. Thus, it may be that orthodontic treatment had raised the perceptions of the dentition of the treated individuals to the same level as the untreated individuals. PMID- 8193981 TI - Development and evaluation of the Oral Health Impact Profile. AB - The capacity of dental clinicians and researchers to assess oral health and to advocate for dental care has been hampered by limitations in measurements of the levels of dysfunction, discomfort and disability associated with oral disorders. The purpose of this research was to develop and test the Oral Health Impact Profile (OHIP), a scaled index of the social impact of oral disorders which draws on a theoretical hierarchy of oral health outcomes. Forty nine unique statements describing the consequences of oral disorders were initially derived from 535 statements obtained in interviews with 64 dental patients. The relative importance of statements within each of seven conceptual subscales was assessed by 328 persons using Thurstone's method of paired comparisons. The consistency of their judgements was confirmed (Kendall's mu, P < 0.05). The reliability of the instrument was evaluated in a cohort of 122 persons aged 60 years and over. Internal reliability of six subscales was high (Cronbach's alpha, 0.70-0.83) and test-retest reliability (intraclass correlation coefficient, 0.42-0.77) demonstrated stability. Validity was examined using longitudinal data from the 60 years and over cohort where the OHIP's capacity to detect previously observed associations with perceived need for a dental visit (ANOVA, p < 0.05 in five subscales) provided evidence of its construct validity. The Oral Health Impact Profile offers a reliable and valid instrument for detailed measurement of the social impact of oral disorders and has potential benefits for clinical decision making and research. PMID- 8193982 TI - Utilisation of dental services in Cambodia and the role of traditional dentists. AB - Cambodia has a small, but growing number of qualified dentists, as well as about 300 traditional dentists. This study describes the current level of utilisation of dental services in Cambodia in Phnom Penh and in 6 provincial areas. 548 adults aged 35-45 and 60-80 years of age were interviewed concerning previous dental attendance, type of service used and preference for qualified or traditional practitioner services. Only 38 per cent had ever had dental treatment, with 87 per cent of attenders last visiting the dentist because of toothache. Although 34 per cent of attenders received their last course of treatment from a traditional dentist, 77 per cent of all subjects said they would prefer to visit a qualified dentist if they had the choice. The role of traditional practitioners may therefore diminish as numbers of qualified dentists increase. PMID- 8193983 TI - Patterns of breast and bottle feeding and their association with dental caries in 1- to 4-year-old South African children. 2. A case control study of children with nursing caries. AB - In a case control study, 109 children with nursing caries (> or = 2 decayed, missing, or filled labial or palatal surfaces of primary incisor teeth) were matched for age, race, gender, and social class to 109 children without nursing caries from the same study areas. Mean dmfs and dmft scores were statistically higher in the nursing caries group but no statistically significant differences were found for feeding patterns between the groups in relation to the prevalence of nursing caries. In the present study nursing caries was found to be unrelated to the length of type of feeding (breast or bottle). PMID- 8193984 TI - The dental caries experience of 5-, 12- and 14-year-old children in Great Britain. Surveys coordinated by the British Association for the Study of Community Dentistry in 1991/92, 1992/3 and 1990-91. AB - A series of caries prevalence surveys across Great Britain has been coordinated by the British Association for the Study of Community Dentistry (BASCD) since 1985/86 with the aim of monitoring caries experience in representative samples of school children aged 5, 12 and 14 years of age. The purpose of this report is to present the findings of the surveys of 14-, 5- and 12-year-old children carried out in 1990/91, 1991/92 and 1992/3 respectively. These point prevalence surveys were conducted at the caries into dentine level of diagnosis using clinical examination only and a standardised, predominantly visual, diagnostic method employed by trained and calibrated teams of examiners from each country/region of Great Britain. For the 14-year-old age group, 114,126 children from 179 health authorities/boards were examined. The weighted mean DMFT for the participating countries and regions was 2.30 (range, 1.42-3.55). At age 5 years, 205,444 children from 184 health authorities/boards were examined. The weighted mean dmft for the participating countries and regions was 1.86 (range, 1.04-2.88). At age 12 years, 151,143 children from 186 health authorities/boards were examined. The weighted mean DMFT for the participating countries and regions was 1.27 (range, 0.84-2.08). A wide geographical variation in the results was evident for all three age groups, demonstrating a consistent north-south pattern, with higher levels towards the north of Britain. Trends in caries experience in permanent teeth indicate that the decline is now much slower for 12-year-old than for 14 year-old children and slower than the rate for 12-year-old children during the previous 4 year interval between examinations. For 5-year-old children, overall, the general decline in caries experience has ceased, while increases in dmft and in proportions with untreated dentinal decay are now seen in most parts of Great Britain. The pattern of restorative care provided has deteriorated with a fall in the care index for 5- and 12-year-old children, this finding may be related to changes in service provision within the UK. PMID- 8193985 TI - The reuse of single-use cardiac catheters: safety, economical, ethical and legal issues. Conseil d'evaluation des technologies de la sante du Quebec. AB - OBJECTIVE: To evaluate the risks, economic benefits, and ethical and legal aspects of reuse of diagnostic and angioplasty catheters intended for single use only. METHODS: Four approaches were used: first, a comprehensive review of the literature relating to risks of infection, pyrogen reactions, toxicity, particulate contamination and catheter breakage; second, experimental studies involving deliberate bacterial contamination and resterilization of catheters; third, experimental studies of the mechanical properties of catheters; and fourth, acquisition of legal opinions. CONCLUSIONS: Diagnostic and angioplasty catheters intended for single use can be reused without putting patients or personnel at increased risk if effective cleaning, sterilizing and quality control procedures are adhered to. An average of five uses for each diagnostic catheter and three uses for each angioplasty catheter may save approximately $5000 and $100,000 respectively, per 100 procedures. The measures necessary to achieve safe reuse, including the steps to assure adequate training of the responsible personnel, should be precisely identified and formally approved by any institution before catheters are reused. Evidence that this has been done and that protocols are being followed should be kept updated and available. PMID- 8193986 TI - Quantitative analysis of the cardiac reserve. AB - OBJECTIVES: Analysis of the left ventricular (LV) pressure-volume loop (P-V loop) to assess LV function. DESIGN: Retrospective study of clinical, hemodynamic and angiographic data of 29 normal individuals and 115 patients with myocardial dysfunction, but no valvular or congenital heart disease. P-V loops were constructed, critically analyzed and compared with the clinical functional status of the patients. MAIN RESULTS: A number of theoretical new concepts was introduced and measured: end-systolic energy (ESE), total LV energy (TE) and potential maximal LV energy (PEmax). These variables were compared with the stroke work, which is neither sensitive nor specific, to separate different stages of cardiac function. ESE, TE and PEmax are sensitive variables, and inversely related to the cardiac reserve. CONCLUSIONS: P-V loops are easy to construct using well recorded hemodynamic and angiographic data. Analysis of P-V loops provides the cardiologist with an overall picture of the myocardial function and reserve. PMID- 8193987 TI - The inefficacy of intravenous propafenone for rate control in atrial fibrillation. AB - The antiarrhythmic agent propafenone has been reported to prolong atrioventricular node conduction and may be suitable for rate control in atrial fibrillation (AF). To evaluate this, 10 patients (seven men and three women aged 29 to 67 years, mean +/- SD 48 +/- 14) were given intravenous propafenone during AF in both the supine and upright positions. Intracardiac catheters measured local electrograms from the high right atrium and right ventricular apex during AF. Atrial rate, ventricular rate and blood pressure were recorded in the control state and after head-up tilt with these measurements repeated after propafenone 1.5 mg/kg was infused over 5 mins. Four of 10 patients reverted to sinus rhythm. Propafenone increased the mean ventricular cycle length (496 +/- 147 versus 556 +/- 152 ms, P = 0.1), although this did not reach significance. In contrast, propafenone markedly increased the mean atrial cycle length (136 +/- 35 versus 226 +/- 39, P < 0.001). The mean ventricular cycle length reverted to baseline after tilt (447 +/- 103 ms) while the mean atrial cycle length decreased but not to baseline levels (170 +/- 21 ms). The authors conclude that intravenous propafenone is generally inadequate for rate control in AF, especially in the upright position. PMID- 8193988 TI - Social inequity in risk of coronary artery disease in Ontario. AB - OBJECTIVES: To examine the distribution of risk factors for coronary artery disease (CAD) by socioeconomic status; to quantify the impact of this distribution on disease incidence; and to estimate by socioeconomic status the proportion of new CAD cases attributable to either smoking or elevated cholesterol. STUDY POPULATION: The overall study population consisted of participants from the Ontario Heart Health Survey (n = 2532) aged 18 to 74 years. A subset of these participants (n = 1293) aged 30 to 74 years, who provided a fasting blood sample for lipid analysis, were used for estimating impact of socioeconomic status on CAD incidence. METHODS: Frequency distributions of risk factors were calculated. The Framingham mathematical model was used to estimate the 10-year probability of developing CAD. Education was selected as the measure for socioeconomic status. OUTCOME MEASURES: Outcomes were prevalence of CAD risk factors, probability of developing CAD and proportion of new cases attributable to smoking and elevated blood cholesterol. MAIN RESULTS: Having an elevated cholesterol level, high blood pressure, diabetes, being overweight or smoking was more prevalent among those with low socioeconomic status. The 10-year probability of CAD was about twice as high among persons with lower education (socioeconomic status) (0.099 low versus 0.055 high). Among males aged 30 to 44 with low socioeconomic status, 26% of the CAD cases were due to smoking versus 13% for those with high socioeconomic status. The values for elevated cholesterol were 19 and 13%, respectively. CONCLUSIONS: Persons with low socioeconomic status are twice as likely to develop CAD because of their higher prevalence of smoking and elevated cholesterol. PMID- 8193989 TI - Some responses of the cardiovascular system to heat and fever. AB - This review outlines the mechanisms of body temperature control and the validity of various sites of measurement of core temperature. The mechanism of fever in response to circulating endotoxins are discussed, and the roles of various peripherally generated pyrogenic cytokines are outlined together with the loci of their action in the brain. The cardiovascular consequences of exposure to heat, particularly the pooling of blood in the skin and the increase of heart rate due to heating of the sinoatrial node, are discussed. The consequences of blood pooling, such as syncope or diminished G tolerance, are very important. Heat exposure and exercise lead to complex circulatory interactions, such as a higher heart rate for a given exercise load in the heat compared with a cool environment. At high work loads there may be a relatively lower cardiac output in hot conditions. Blood lactate levels and rectal temperature tend to be higher in exercise in the heat than exercise in the cold. Fever causes a large renal vasodilation and hepatic vasodilation, which are humorally mediated and which effectively cause a splanchnic vascular shunt of some consequence if there is already heart failure or shock. Syncope during fever, endotoxin shock and the role of pyrogens in heat stroke are discussed. PMID- 8193990 TI - Apolipoprotein A-II: a protein in search of a function. AB - OBJECTIVE: To summarize current findings relevant to the function of apolipoprotein A-II (apoA-II), a major protein component of high density lipoproteins (HDL). STUDY SELECTION: Studies relating to the structure, regulation and genetics of apoA-II are reviewed. These include studies of apoA-II expression in humans and mouse animal models. All studies cited were published between 1972 and 1993. CONCLUSIONS: Since its discovery over 20 years ago, apoA II has been a protein in search of a function. In fact, it has often been stated that apoA-II has no major function in plasma lipoprotein metabolism. While it is clear that apoA-II does not serve an essential function in HDL metabolism, the evidence overwhelmingly indicates that apoA-II importantly influences HDL functional states and suggests strongly that apoA-II is likely to contribute to atherogenesis. PMID- 8193991 TI - Experimental evidence that rejection, but not transplantation, modulates coronary reactivity to direct and indirect vasodilation. AB - OBJECTIVE: To investigate the coronary response to direct and indirect vasodilation in a canine model of orthotopic heart transplantation because of the potential benefits of preserved vascular function during rejection. In cardiac transplants, reversal of vascular abnormalities is considered to be of prime importance for recovery from graft failure and rejection. DESIGN: Cardiac function and coronary bloodflow were monitored with electromagnetic flow probes. Hemodynamic data were collected either postoperatively, at the height of the recovery period, or during the severe rejection phase. Nitroglycerin (n = 7) as a 5 micrograms/kg intravenous bolus and diltiazem (n = 5) as a 150 micrograms/kg intravenous bolus were administered as direct stimulants of the coronary vasculature. Ouabain (n = 7), a digitalis derivative, at 20 micrograms/kg/min and calcium gluconate (n = 9) at 0.05 mEq/kg were given as indirect coronary vasodilators. Amrinone (n = 6), having both vasodilator and inotropic properties, was also studied (0.75 mg/kg intravenous bolus followed by a 200 micrograms/kg infusion). RESULTS: Under control conditions, all drugs significantly increased coronary bloodflow: nitroglycerin +47%, diltiazem +33%, ouabain +25%, calcium gluconate +36% and amrinone +65%. Coronary vascular resistance was reduced by a similar magnitude in all cases. In the rejection phase, ouabain and calcium gluconate, despite increasing stroke work, failed to induce significant changes in coronary bloodflow. Among the direct vasodilators used, only nitroglycerin augmented coronary perfusion (+38%) during rejection; the magnitude of its action on coronary vascular resistance was similar to that observed under control conditions. CONCLUSIONS: These results suggest that transplantation per se does not interfere with the response to either direct or indirect coronary dilation. Severe rejection blunted indirect coronary dilation. In these conditions, inotropic challenges appear to be detrimental. The observation that the coronary vasculature remained sensitive to nitroglycerin despite severe rejection suggested that a drug-specific coronary vasodilator reserve is still present. This study provides valuable arguments for the use of vasodilator therapy during graft rejection since rejection and ischemia are intimately related. PMID- 8193992 TI - Altered neuropeptide Y effects on noradrenaline levels in the paraventricular nucleus of rats following aortic constriction. AB - OBJECTIVE: To clarify whether central catecholamine systems are modulated by neuropeptide Y (NPY) soon after imposing an increased pressure overload on the heart. Recent evidence supports the view that the sympathetic nervous system actively participates in the development of cardiac hypertrophy. Since noradrenaline-containing neurons involved with cardiovascular regulation within the brain are known to coexist with NPY, it is possible that a functional interaction between NPY and noradrenaline exists centrally. DESIGN: The paraventricular nucleus (PVN) of aortic-banded Sprague-Dawley rats were sampled for noradrenaline levels using in vivo microdialysis and compared with samples taken from sham-operated controls. Autoradiographical localization of NPY receptors in the PVN was also carried out between animal groups. ANIMALS: Forty eight Sprague-Dawley rats (weighing between 175 and 200 g). INTERVENTIONS: The 48 rats were randomly divided into two groups. One group underwent abdominal suprarenal aortic constriction. The control group underwent the same procedure without being banded. At 14 days postsurgery, the animals had microdialysis probes stereotaxically implanted into the PVN under anesthesia. A solution of NPY (10(-8) M) was perfused through the probe for 20 mins, and catecholamine levels were measured in the resulting perfusate. MAIN RESULTS: Extracellular noradrenaline concentrations in the PVN were found to be increased following aortic constriction compared with sham controls (P < 0.05). Infusion of NPY resulted in a reduction of noradrenaline concentration in sham animals (P < 0.05), whereas no change in noradrenaline concentration was evident in the aortic constricted group. Autoradiography of NPY receptors in the PVN showed a significant decrease in the receptor density in aortic-constricted rats versus sham controls (P < 0.05). CONCLUSIONS: The results strongly support the view that NPY plays an important neuromodulatory role in the PVN regarding control of sympathetic output. It is suggested that cardiac hypertrophy may be precipitated secondary to changes in brain NPY levels and increased sympathetic activity. PMID- 8193993 TI - Effect of parathyroid hormone on myocardial bloodflow and infarct size following coronary artery occlusion in the dog. AB - OBJECTIVE: To investigate the cardioprotective effect of both the amino terminal of bovine parathyroid hormone (bPTH-[1-34]) and human parathyroid hormone (hPTH [1-84]) following coronary artery occlusion. DESIGN: Animals were randomly assigned to one of three treatment groups following circumflex coronary artery occlusion. ANIMALS: Experiments were performed using 19 mongrel dogs of either sex. As four animals died during experimentation, data are shown for 15 dogs (n = 5 for each treatment group). INTERVENTIONS: Animals received saline, bPTH-(1-34) or hPTH-(1-84) following occlusion of the circumflex coronary artery. Peptides were given at 0.008 nmol/kg/min. All treatments were infused directly into the coronary circulation. Infusion rate was 1 mL/min for 10 mins at 30 min intervals until the end of the experiment (480 mins after onset of occlusion). Hemodynamic variables were monitored throughout the experiment. Radioactive microspheres were injected 10 mins before, and 30, 240 and 480 mins following, occlusion of the coronary vessel to determine regional myocardial blood-flows. At the end of the experiment, area at risk and infarct size were measured by simultaneous infusion of Evans blue dye and triphenyl tetrazolium chloride stain. MAIN RESULTS: Neither bPTH-(1-34) nor hPTH-(1-84) significantly reduced area of risk or infarct size as a percentage of area at risk compared with controls. These results were corroborated by regional blood-flows measured using radioactive microspheres. There was no significant difference in hemodynamic variables among the groups except that left atrial pressure was consistently lower following treatment with hPTH-(1-84). CONCLUSIONS: No evidence was found that either bPTH-(1-34) or hPTH (1-84) salvaged ischemic myocardium in a canine model of myocardial infarction. Treatment with hPTH-(1-84) was associated with a reduction in left atrial pressure. This latter phenomenon may constitute a beneficial effect of this peptide on diastolic myocardial function. PMID- 8193994 TI - Unilateral termination of treatment by a psychiatrist. Guidelines of the Canadian Psychiatric Association. PMID- 8193995 TI - Therapeutic efficacy of specific serotonin reuptake inhibitors (SSRIs) in dysthymia. AB - Pharmacological treatment of dysthymia is a contentious issue mainly because of the traditional view that this disorder has characterological origins and responds to psychotherapy. However, Akiskal's subtyping of primary dysthymia, which was based in part on its response to older antidepressants, can assist in the prediction of responses to antidepressants. Specific serotonin reuptake inhibitors (SSRIs) have equal efficacy but fewer adverse effects and greater tolerability than older antidepressants. Therefore, SSRIs appear to be a viable treatment option for these patients although there are few documented systematic studies of the use of these agents in primary dysthymia. An open study was conducted to determine the efficacy of fluoxetine in primary dysthymia (DSM-III-R and Akiskal's criteria). A good response was observed in the subaffective subtype but not in the character spectrum group. Overall, the antidepressant was tolerated well, with significant adverse effects reported and responders showing reductions in both depressive and anxious symptoms. These initial findings indicate a potential role for SSRIs in the pharmacotherapy of dysthymia. PMID- 8193996 TI - [Organic personality syndrome in multiple sclerosis and effect of stress on recurrent attacks]. AB - This study focuses on a sample of 35 patients who had recently suffered an attack of multiple sclerosis. They were first subjected to the so-called life stress method in order to look for a connection between life stresses and the attacks of multiple sclerosis. The sample was compared with a paired control population composed of patients recruited from admission departments and medical emergency departments. The AMDP psychopathological evaluation method was applied to the sample, to establish a characteristic mental profile of these patients. Three types of results are highlighted. First, the comparison of the event scores shows a significant difference between the population of patients suffering from an outbreak of multiple sclerosis and the control population. A connection between "life stresses" and the triggering of the outbreaks of multiple sclerosis is therefore mentioned and discussed. Second, the application of the system of the Association de methodologie et de documentation psychiatrique brings out a mental profile common to patients suffering from multiple sclerosis, consisting of a very specific association of mood disorders: dysphoria, euphoria and mania on the one hand, and depression, anxiety and dramatization on the other, with relative anosognosia. The correlation between dysphoria, the syndrome's principal characteristic, and the event score adds another argument in favour of the connection between life stresses and the evolution of the disease. The main components of this mental profile are primarily correlated with the existence of a neuropsychology suggestive of a medial basal frontal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8193997 TI - Stressful life events associated with adolescent suicide attempts. AB - This study was designed to examine the types of stressful events that are related to adolescent suicidal behaviour. Adolescent inpatients who attempted suicide and a control group of high school students were compared on various types of stressors. The stressors were categorized according to their type (for example, discrete events versus chronic strains) and source (for example, family or friends). Compared to high school controls, adolescents who attempted suicide reported elevated levels of major negative events and exit events. Both chronic strains and discrete stressors were related to an increased severity of depression and suicidal ideation. The results support the notion that increased stress is related to adolescent suicidal behaviour. Different approaches to categorizing stress may improve the understanding of the relationship between stressful life events and suicide. Also, sex differences may influence the relationship between life stress and suicidal feelings. PMID- 8193998 TI - [Validation of an eating attitude scale in a French-speaking Quebec population]. AB - The Eating Attitudes Test (EAT-26) is one of the most frequently used screening questionnaires for anorexia and bulimia nervosa for use with clinical and general populations. Although the psychometric qualities of the instrument have been reported for the English version, little has been done to date to validate a French version. A french version of the EAT-26 was distributed to anglophone students and francophone students, as well as anglophone and francophone patients. Overall, the results demonstrated that the authors' French version has the same psychometric characteristics as the English version when used with clinical and non clinical populations. The overall test and its subscales differentiated between patients and non patients similarly in both linguistic groups. The internal consistency of the two versions, as assessed by Cronbach's alpha, was comparable. Among female high-school students, 14.1% of the anglophone students and 14.3% of the francophone students scored above the cutoff score for significant eating disorders behaviour. PMID- 8193999 TI - Chronic carbon monoxide poisoning. PMID- 8194000 TI - Geriatric psychiatry training: the starting point. PMID- 8194001 TI - Iron overload and psychiatric illness. AB - Seven patients with varying psychiatric disorders were found to have iron overload as manifested by abnormal serum ferritin, transferrin saturation index (TSI), or excessive urinary iron. All possible sources of secondary iron overload were ruled out. The patients were treated with the specific iron chelator, deferoxamine, given IM for seven to 22 weeks which resulted in significant clinical improvements. These cases indicate a need to be aware that disordered iron metabolism is a somatic cause of psychiatric illness and that there is clinical improvement upon lowering elevated iron levels in patients with iron overload. PMID- 8194002 TI - The role of multimodal therapy in the treatment of hepatocellular carcinoma. PMID- 8194003 TI - Metastasizing low grade gliomas in children. Redefining an old disease. PMID- 8194004 TI - Nucleolar organizer regions in lining epithelium adjacent to squamous cell carcinoma of human oral mucosa. AB - BACKGROUND: The value of silver staining of nucleolar organizer regions (AgNOR) counts as a diagnostic aid has been reported for several neoplastic entities. Previous studies have proved the value of the morphometric evaluation of AgNOR in the detection of incipient cellular alterations. METHODS: A morphometric analysis of AgNORs was performed in oral mucosa epithelium adjacent to squamous cell carcinoma compared with normal mucosa epithelium and the carcinomatous parenchyma. RESULTS: Highly statistically significant differences in all 5 AgNOR related parameters assessed were found between normal mucosa and mucosa adjacent to cancer. Conversely, the corresponding nuclear parameters failed to exhibit significant differences. The parameter AgNOR contour index plotted for individual cases affords a cutoff value that could prove useful in identifying epithelia at early stages of transformation. CONCLUSIONS: AgNOR evidenced significant variations in epithelium adjacent to oral squamous cell carcinoma, which did not exhibit morphologic signs of atypia. Based on this study, AgNOR would be a quantitative, discriminative aid, easy to monitor in a pathology laboratory, in detecting incipient cellular alterations. These findings contribute to the issue of early diagnosis and to the knowledge of tumoral growth. PMID- 8194005 TI - Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. AB - BACKGROUND: The benefits of preoperative chemotherapy and radiation for esophageal carcinoma are under investigation. A pilot study was undertaken to determine if pathologic assessment of tumor regression correlated with disease free survival. METHODS: Ninety-three resected specimens from patients treated with cis-dichloro-diamino cisplatin and irradiation before surgery were examined on semiserial sections. Patients selected for surgery were all Status 1 according to the World Health Organization (WHO) classification. Histologic typing was based on the WHO classification. Tumor regression grade (TRG) was quantitated in five grades: TRG 1 (complete regression) showed absence of residual cancer and fibrosis extending through the different layers of the esophageal wall; TRG 2 was characterized by the presence of rare residual cancer cells scattered through the fibrosis; TRG 3 was characterized by an increase in the number of residual cancer cells, but fibrosis still predominated; TRG 4 showed residual cancer outgrowing fibrosis; and TRG 5 was characterized by absence of regressive changes. Survival curves were estimated according to the Kaplan-Meier method. A quantification of the relationship between treatment failure and confounding variables (age, tumor location, tumor size, esophageal wall involvement by residual cancer and/or regressive changes, histology, treatment, adequacy of surgery, pathologic lymph node status, and tumor regression grade) was done using Cox's proportional hazards model. RESULTS: Forty-two percent of specimens were TGR 1-2; 20%, TGR 3; and 33%, TGR 4-5. Univariate analysis found that tumor size, pathologic lymph node status, tumor regression grade, and esophageal wall involvement were highly correlated with disease free survival (P < 0.05). After multivariate analysis, only tumor regression (i.e., TRG 1-3 versus TRG 4-5) remained a significant (P < 0.001) predictor of disease free survival. CONCLUSIONS: This study highlights the importance of tumor regression in the survival of patients with esophageal carcinoma treated with preoperative chemoradiotherapy. These findings suggest that tumor regression grade should be considered when evaluating therapeutic results. PMID- 8194006 TI - Prevalence and clinicopathologic features of multiple squamous cell carcinoma of the esophagus. AB - BACKGROUND: The occurrence of independent synchronous esophageal carcinoma in patients with grossly invasive esophageal cancer (GEC) is well known. Although multiple primary carcinoma of the esophagus is not uncommon, the exact prevalence is controversial, and its clinicopathologic features remain relatively unknown. METHODS: Fifty-four patients with squamous cell GEC who underwent transthoracic esophagectomy with systematic lymphadenectomy between 1987 and 1991 at the Institute for Digestive Diseases, Belgrade University Clinical Center, were included in the study. RESULTS: Detailed histopathologic examination of the esophagus resected for squamous cell carcinoma was performed in 54 patients and revealed 17 patients (31%) with associated cancer independent of the main tumor. The second lesion was significantly less invasive than the main tumor. There was no significant difference (P = 0.06) in sex, age, main tumor site, tumor differentiation, tumor diameter, lymph node involvement, or tumor stage between patients with multiple cancer and patients with solitary cancer, but there was a significant difference in the depth of invasion (P < 0.01). The tumor stage in patients with multiple cancer was determined by the main tumor stage and was not influenced by the associated lesion. The prevalence of multiple primary cancer of the esophagus is lower in other reports than in this series. CONCLUSIONS: The patients in this study had significantly more invasive main tumors. It seems likely that a higher prevalence of multiple cancer may be expected in patients with advanced main tumor penetration. These results support the concept that the entire esophagus may be considered as one entity of field cancerogenesis. PMID- 8194007 TI - Possible role of Helicobacter pylori infection in early gastric cancer development. AB - BACKGROUND: Gastric cancer is the most frequently diagnosed malignancy in Japan. The possible relationship between Helicobacter pylori infection and gastric cancer in Japan was evaluated. METHODS: H. pylori infection was identified by the presence of anti-H. pylori IgG. The frequency of H. pylori infection was compared in 213 patients with gastric cancer and the same number of asymptomatic control subjects matched for age and sex. RESULTS: The presence of IgG antibody to H. pylori was significantly more prevalent (P < 0.001) in those with gastric cancer compared with asymptomatic control subjects (88.2% versus 74.6%). H. pylori positive rates were significantly greater in patients with the intestinal type (90.4%, P < 0.001) and diffuse type (86.4%, P < 0.05) of gastric cancer than in control subjects. Ninety-three percent of the patients with early gastric cancer tested positive for H. pylori (P < 0.001 compared with control subjects), whereas no significant difference was observed between those with advanced gastric cancer and control subjects. The intestinal type of early gastric cancer showed only the significantly increased frequency of high titer (optical density > 1.50) of H. pylori IgG antibody (P < 0.001) compared with control subjects without cancer. CONCLUSIONS: These results suggest that H. pylori infection may be associated with the development of early gastric cancer in Japan. PMID- 8194008 TI - Serum pepsinogen as a new marker for gastric carcinoma among young adults. Research Group on Prevention of Gastric Carcinoma among Young Adults. AB - BACKGROUND: Gastric carcinoma is relatively uncommon in Japan among persons younger than 40 years of age, but its prognosis is not favorable and it affects young adults in their most productive years. This study was performed to evaluate the validity of serum pepsinogen as a new marker for gastric carcinoma among Japanese younger than 40 years of age. METHODS: Data and sera were collected from the patients (108 patients younger than 40 years of age with gastric carcinoma from nine hospitals in the Kanto-Shin'etsu area in Japan) and from the control subjects (108 hospital control subjects and 108 screening control subjects) whose sex and age (within 4 years) were matched. Pepsinogen I and pepsinogen II values were measured and compared between patients and control subjects by paired t test. Sensitivities and specificities when criteria were defined by pepsinogen I, pepsinogen II, and pepsinogen I/II ratio were calculated. RESULTS: The pepsinogen I and pepsinogen II levels among patients were higher and the pepsinogen I/II ratio among patients was lower than among control subjects. When a pepsinogen II level higher than 14.8 ng/ml was considered positive, the test showed high sensitivity (83.3% for total gastric carcinoma and 85.0% for early gastric carcinoma) and high specificity (76.9% for hospital control subjects and 75.0% for screening control subjects). Similar degrees of sensitivity and specificity were obtained with the pepsinogen I/II ratio. CONCLUSIONS: These results suggest that a high pepsinogen II level combined with a low pepsinogen I/II ratio may be a useful screening test for gastric carcinoma in a young population at high risk for gastric carcinoma. This impression should be confirmed by a more extensive field trial to determine whether performance of these assays promotes early diagnosis of gastric carcinoma. PMID- 8194009 TI - Correlation of preoperative carcinoembryonic antigen levels and prognosis of gastric cancer patients. AB - BACKGROUND: The prognostic significance of preoperative serum carcinoembryonic antigen (CEA) determination in patients with gastric cancer has been controversial. METHODS: The correlation between preoperative serum CEA levels and clinicopathologic factors was evaluated in 865 patients with gastric cancer who underwent gastrectomy between 1980 and 1990. The authors also investigated whether preoperative CEA levels represented a prognostic parameter using Cox's proportional hazard model. RESULTS: Of the 865 patients, 249 (28.8%) were positive for CEA. The positivity rate was higher in the elderly, in male patients whose tumors were located in the lower third of the stomach, and in those with Borrmann types 2 and 3. It was also significantly correlated with tumor size, depth of invasion, lymph node metastasis, peritoneal and liver metastases, and cancer stage. The higher the serum CEA level, the more advanced the cancer stage, and the rate of curative resection also decreased as CEA levels were elevated. There was a significant difference between patients with CEA levels below 10 ng/ml and those with levels exceeding 10 ng/ml with regard to tumor progression and curability. Multivariate analysis showed a strong and highly significant association between preoperative serum CEA level and survival time. The prognosis was also significantly poorer when the CEA level was above 10 ng/ml, even in patients in the same stage (Stages 1, 2, and 3). CONCLUSIONS: Preoperative serum CEA determination in patients with gastric cancer valuable for predicting tumor progression and prognosis. Further, in patients in Stages 1, 2, and 3, CEA levels exceeding 10 ng/ml are clinically significant and provide more prognostic information than that obtained by conventional staging methods. PMID- 8194010 TI - A proposed staging system for primary gastric lymphoma. AB - BACKGROUND: Although primary gastric lymphoma is the most common extranodal lymphoma, no specific staging system exists. METHODS: The authors reviewed 98 cases histologically classified according to the Working Formulation, including low grade B-cell lymphoma of mucosa-associated lymphoid tissue type. Survival rates were calculated by the Kaplan-Meier method according to T, N, and M of the general rules of the International Union Against Cancer TNM system. The definitions of these categories are as follows: T1, tumor invades the lamina propria or submucosa; T2, the muscularis propria; T3, the subserosa; T4, the serosa without invasion of adjacent structures; T5, adjacent structures; N0, no regional lymph node metastasis; N1, perigastric lymph nodes within 3 cm of the edge of the primary tumor; N2, perigastric lymph nodes more than 3 cm from the edge of the primary tumor or in lymph nodes along the left gastric, common hepatic, splenic, or celiac arteries; N3, paraaortic and hepatoduodenal lymph nodes and/or other intraabdominal lymph nodes; N4, beyond N3; M0, no distant metastasis; and M1, positive. RESULTS: The overall 5-year survival rate was 83.5%; it was 100% in T1, 82.4% in T2, 84.2% in T3, 52.9% in T4, and 33.3% in T5; 93.9% in N0, 90.5% in N1, 66.2% in N2, and 44.4% in N3/N4; and 86.0% in M0 and 25.0% in M1. Based on these results, the authors proposed a new staging system as follows: Stage I, T1/N0, N1/M0; Stage II, T1/N2/M0, T2,T3/N0,N1,N2/M0; Stage III, T4,T5/any N/M0, any T/N3, N4/M0; and Stage IV, any T/any N/M1. According to this system, the 5-year survival rate significantly decreased as the stage progressed: 100% in Stage I, 88.9% in Stage II, 52.1% in Stage III, and 25.0% in Stage IV. In Stages I and II, survival rates were not significantly different whether chemotherapy was done or not, whereas in Stage III all patients treated with surgery alone died. CONCLUSIONS: This staging system is useful for assessing prognosis of and deciding a therapeutic plan for primary gastric lymphoma. PMID- 8194011 TI - Selection factors for local excision or abdominoperineal resection of early stage rectal cancer. AB - BACKGROUND: This study reviews the experience of patients with early stage rectal cancer managed by local excision or abdominoperineal resection to clarify the relative indications and results of these two approaches. METHODS: From 1962 to 1991, 125 patients with T1 and T2 rectal cancer underwent local excision (56 patients) or abdominoperineal resection (69 patients). Outcome was analyzed by stage, treatment, and pathologic features of tumor grade and vessel involvement. RESULTS: The 5-year actuarial recurrence-free survival and local control was 87% and 96%, respectively, for 28 patients undergoing local excision with favorable histologic features (well or moderately well differentiated histologic findings without venous/lymph vessel involvement). These results were 57% and 68% for 28 patients with unfavorable histologic features (poorly differentiated histology and/or venous/lymph vessel involvement). For patients undergoing abdominoperineal resection, the 5-year actuarial recurrence-free survival and local control of 49 patients with favorable histologic features was 91% and 91%, respectively. These results were 79% and 89%, respectively, for patients with poorly differentiated histology or venous/lymph vessel involvement. CONCLUSIONS: For patients with T1 and T2 tumors having favorable histologic features, a satisfactory survival and local control was achieved for patients undergoing local excision or abdominoperineal resection. In contrast, patients with T1 and T2 tumors having poorly differentiated histologic features and/or venous/lymph vessel involvement undergoing local excision or abdominoperineal resection appeared to have decreased rates of survival and of local control. For these patients, radical resection combined with pelvic irradiation and 5-fluorouracil-based chemotherapy should be investigated. PMID- 8194012 TI - Multimodal adjuvant treatment and liver transplantation for advanced hepatocellular carcinoma. A pilot study. AB - BACKGROUND: Orthotopic liver transplantation has been used in a large number of patients with primary liver cancer because it increases the possibilities of resection of large tumors. Despite isolated cases of prolonged survival, however, the results of liver transplantation for advanced tumors have been universally disappointing because of high rates of tumor recurrence. In an attempt to reduce the recurrence rate, a pilot study testing a multimodal adjuvant treatment in patients undergoing liver replacement for hepatocellular carcinoma was undertaken. METHODS: The treatment consisted of preoperative hepatic arterial chemoembolization (iodized oil, doxorubicin, and gelatin sponge) and radiotherapy (5 Gy in one fraction immediately before surgery), and postoperative systemic chemotherapy with mitoxantrone. Nine patients entered this study. The tumor was solitary in two cases (5 cm and 8 cm) and multifocal in seven cases (2-9 nodules, 3-9 cm). The postoperative TNM stages were II in one case, III in one case, and IVA in seven cases. RESULTS: Chemoembolization and radiotherapy were performed in seven cases each (five patients had both treatments). All patients underwent liver transplantation with conventional immunosuppression. One patient died of heart failure 4 days after surgery. The remaining eight patients received 4 to 10 courses of chemotherapy (mean 9). The main toxicity of chemotherapy was leucopenia. Two patients died of recurrence: one at 7 months and one at 11 months. Six patients are alive, five of them without evidence of disease, with a mean follow-up of 30 months (range 16-45) after liver transplantation. The 3-year actuarial survival is 64%. CONCLUSIONS: These results show that an aggressive adjuvant therapy can be used in association with liver transplantation in the treatment of advanced hepatocellular carcinoma without increased mortality and suggest that such a protocol could be effective in preventing tumor recurrence. PMID- 8194013 TI - K-ras codon 12 mutations in biliary tract tumors detected by polymerase chain reaction denaturing gradient gel electrophoresis. AB - BACKGROUND: Although the prevalence of K-ras codon 12 mutations in biliary tract (BT) tumors has been addressed in previous studies, the results have shown large discrepancies in mutation frequency. METHODS: K-ras codon 12 mutations were investigated by polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE), a sensitive method for detecting DNA base changes, in a large series of BT tumors. RESULTS: In A-549 cells, which are known to contain a G to A change at the first base of K-ras codon 12, the mutation could be detected by DGGE even after 1:16 dilution with normal DNA. Tumor samples were microdissected from paraffin embedded tissue sections to ensure the presence of the tumor cells. K-ras mutations were detected in 13 of 23 bile duct tumors (56.5%) and in 9 of 23 gallbladder tumors (39.1%) by DGGE. However, no mutations were detected in normal, hyperplastic, and dysplastic BT epithelium or in tumorlike lesions, such as adenomyomatous hyperplasia, cholesterol polyps, and cystitis glandularis proliferans. The samples exhibiting abnormalities on DGGE showed a base change at K-ras codon 12 when examined by oligonucleotide hybridization. CONCLUSIONS: K-ras codon 12 mutations are seen often in BT tumors, and a combination of microdissection and PCR-DGGE is an effective approach for their detection. PMID- 8194014 TI - Basaloid bronchial carcinoma. A histologic group with a poor prognosis. AB - BACKGROUND: Basal cell carcinomas (BCCs) have been described in various locations, such as skin, anal canal, tongue, larynx, and recently, the lungs. These tumors seem to have a poor prognosis. METHODS: A series of 115 surgically resected lung tumors, previously classified as poorly or undifferentiated carcinoma, were reviewed retrospectively. From these, 37 cases were reclassified as BCCs and were compared in terms of clinical features and survival, with 40 cases reclassified as poorly differentiated squamous cell (PDSC) carcinoma of the lung. RESULTS: There was no difference between the groups regarding age, clinical presentation, pattern of relapse, and cause of death. Median and overall survival were different between the two groups, especially for Stage I and II patients: 5 year actuarial survival in the BCC group was 15% and in the PDSC group 47% (P = 0.004). CONCLUSIONS: This subset of non-small cell lung cancer (NSCLC) has a worse prognosis than other NSCLC, and this should be considered in survival studies and new treatment trials. PMID- 8194015 TI - Human papillomavirus not found in squamous and large cell lung carcinomas by polymerase chain reaction. AB - BACKGROUND: Human papillomavirus (HPV) has been identified not only in anogenital carcinomas, but also in malignancies of other organs, including bronchogenic carcinomas. Previous studies reporting detection of these viruses in lung cancers used mainly in situ hybridization. The authors applied the polymerase chain reaction (PCR) for investigating the occurrence of HPV in bronchial neoplasms. METHODS: Formalin fixed, paraffin embedded tissues of 40 squamous and 7 large cell lung cancers were examined. PCR was done with consensus primers, capable of detecting HPV 6, 11, 16, 18, 31, 33, 52b, and 58. RESULTS: None of the 47 samples contained any of the examined HPV types. CONCLUSIONS: Because the squamous and large cell cancer cases were found not to be associated with HPV infection, this study does not support the potential role of these viruses in the development of lung cancers. PMID- 8194016 TI - Significance of soluble interleukin-2 receptor levels for evaluation of the progression of adult T-cell leukemia. AB - BACKGROUND: The authors conducted a survey of a large cohort of patients with adult T-cell leukemia (ATL) and a group of human T-cell leukemia virus type 1 (HTLV-1) carriers to elucidate whether measurements of soluble interleukin-2 receptor (sIL-2R) levels are indicative of ATL tumor burden and correlate with clinical progression. METHODS: Using a sandwich enzyme immunoassay, the authors determined sIL-2R in the serum of 135 patients with ATL diagnosed and subclassified according to the Japan Lymphoma Study Group criteria and in the serum of healthy HTLV-1 seropositive persons. Also included were patients in the preleukemic state of ATL (pre-ATL), which is characterized by only slight blood changes but does not fit the diagnostic criteria of ATL. In the five subjects who finally advanced to overt ATL, the authors prospectively performed serial measurements of the receptor. RESULTS: Serial measurements of sIL-2R levels taken until overt ATL developed showed that these levels in the initial samples were higher than those of control subjects, even when subjects were asymptomatic or in the pre-ATL state. The serial levels of the five subjects gradually increased despite being in a clinically stable condition, finally reaching markedly high levels at the time ATL became overt. The mean sIL-2R levels of the smoldering, chronic, acute, and lymphoma subtypes of ATL were 1680 U/ml, 6680 U/ml, 45,940 U/ml, and 34,620 U/ml, respectively (P < 0.01). The sIL-2R levels of each subtype at the time of diagnosis were more correlated with tumor burden, malignant behavior, and prognosis than lactate dehydrogenase (LDH) levels. In the low, moderate, and high sIL-2R subgroups, the median survival time and percent survival probability at 2 years was 30.2 months (46.0%), 16.5 months (25.0%), and 7.7 months (15.3%), respectively. CONCLUSIONS: Serial measurements of sIL-2R levels are of clinical importance because changes of the levels correlate with disease progression, especially in early phase of ATL. The data suggest that sIL 2R may be more useful than LDH. In addition, emphasis may be placed on sIL-2R as an indicator of ATL progression status and prognosis for survival. The value of this marker in clinical practice should be confirmed prospectively. PMID- 8194017 TI - The carcinogenic risk of treatments for severe psoriasis. Photochemotherapy Follow-up Study. AB - BACKGROUND: Common treatments used for severe psoriasis include psoralen and ultraviolet A radiation (PUVA), methotrexate, ultraviolet B (UVB), and tar. These therapies are often used for prolonged periods and may be carcinogenic. METHODS: For more than 13 years, the authors have prospectively determined the incidence of skin cancer and use of treatments for psoriasis in a 1380 patient cohort originally enrolled in a therapeutic trial of PUVA at 16 university centers. RESULTS: Squamous cell carcinoma (SCC) developed in more than one fourth of patients exposed to high doses of PUVA. In this group, the standard morbidity ratio for these tumors was 83 (95% confidence interval [CI], 72-96) compared with the expected number of these tumors in the general population. High-level exposure to methotrexate is a significant independent risk factor for developing SCC (relative risk, 2.1 for high versus low or no exposure; 95% CI, 1.4-2.8). Metastatic disease developed in seven patients with SCC. No significant increase in the risk of SCC was associated with long term exposure to UVB or topical tar, and no substantial increase in the risk of basal cell carcinoma was noted in association with prolonged use of any of these treatments. CONCLUSIONS: Long term exposure to PUVA and methotrexate significantly increases the risk of SCC in patients with psoriasis. This risk should be considered in selection of treatment. The ultimate morbidity of these tumors is undetermined. PMID- 8194018 TI - Histologic grading of breast carcinoma. A reproducibility study. AB - BACKGROUND: A concern with the histologic grading of breast cancer is that tumor grading is a subjective evaluation that may have problems with reproducibility. METHODS: A single slide from 10 invasive breast cancers was submitted to 25 pathologists who practice in six separate groups. Pathologists graded the tumors using a modified Bloom-Richardson (B-R) scheme, and the results were compared. RESULTS: In 8 of the 10 cases, there was greater than 87% agreement by the pathologists as to the final combined B-R grade, with complete agreement in 2 cases. Only one case had any discrepant opinions that ranged from low to high grade, and this involved only 3 of the 25 pathologists. With respect to B-R score, the pathologists tended to score the tumors as either one of two adjacent scores. Due to this clustering, the B-R scheme appears reproducible into five groups: very low and very high grade tumors and B-R score "5,6," "6,7," and "7,8" tumors. This clustering was especially noticeable in two cases with split decisions, in which the discrepancy in final combined grade was largely due to the tumors being given B-R scores that straddled and were then condensed into two B-R grades. A consensus from each pathology group tended to merge with the majority opinion of all 25 pathologists and was correct for outliers. CONCLUSIONS: This study indicates that reproducibility of grading breast cancers can be achieved when a histologic grading scheme with specified guidelines is used. Pathologists must be aware of the limits of reproducibility, with appropriate guidelines being followed to help optimize agreement, and there should be an awareness of how pathologists group in their evaluations. Also, it may be advisable to better correlate or link reproducibility data with prognostic data in the design of grading schemes. PMID- 8194019 TI - Endometrial adenocarcinoma presenting as an isolated calcaneal metastasis. A rare entity with good prognosis. AB - A 59-year-old woman presented with progressive pain, swelling, and erythema of her right foot. Biopsy of a destructive calcaneal lesion revealed a metastatic adenoacanthoma with focal adenosquamous carcinoma consistent with an endometrial origin. This was confirmed on hysterectomy. Postoperative treatment consisted of systemic chemotherapy, hormonal therapy, and local radiotherapy to the foot. She has now experienced 5 years of complete remission. This is a case of an endometrial adenocarcinoma presenting as an isolated calcaneal metastasis with an excellent outcome. PMID- 8194020 TI - Distinctive flow histogram pattern in molar pregnancies with elevated maternal serum human chorionic gonadotropin levels. AB - BACKGROUND: Flow cytometric analysis of trophoblastic tissue has shown that most partial hydatidiform moles (PMs) are triploid, whereas most complete moles (CMs) are diploid or tetraploid. Ploidy analysis can support a diagnosis of CM or PM. However, in some cases, a precise diagnosis cannot be rendered. METHODS: This study examined DNA flow histograms in 86 cases of histologically diagnosed moles and nonmoles to identify patterns specific to moles to eliminate indeterminate diagnoses. Forty hydropic abortions, 17 CMs, and 29 PMs were analyzed, and results were correlated with microscopic appearance and maternal serum human chorionic gonadotropin (HCG) levels. RESULTS: Analysis of nondiploid histologic moles in which the initial maternal serum HCG level was greater than 150,000 mIU/ml showed similar histograms in 12 of 14 cases. In these 12 specimens, a distinct aneuploid peak could not be delineated from multiple cell populations between the G0/G1 and G2/M or G0/G1diploid and G0/G1aneuploid peaks. This commonly appeared as a slope rising toward the tetraploid region. S-phase fraction values showed a trend toward higher values in the moles versus nonmoles, but the difference was not statistically significant. CONCLUSIONS: This sloping histogram pattern may reflect progression from a single aneuploid to multiple aneuploid populations. Its statistically significant correlation (P < 0.001) with high maternal serum HCG values suggests the presence of a highly metabolically active population of aneuploid trophoblast. Because it appears specific to nondiploid moles, recognition of the pattern will aid in the distinction of mole from hydropic spontaneous abortion. PMID- 8194021 TI - Quality of life of patients with prostate cancer and their spouses. The value of a data base in clinical care. AB - BACKGROUND: Because of the dearth of information concerning the quality of life of patients with prostate cancer, a data base was established to examine the nature and extent of problems in patients' and spouses' adaptation and their interrelationships and to examine the effect of disease stage combined with treatment regimen on patients' quality of life. METHODS: One hundred seventy-two patients and 83 spouses/partners completed quality of life questionnaires in a prostate cancer health education lecture series. The measures used were the European Organization for Research and Treatment of Cancer (EORTC) Prostate Cancer Quality of Life Questionnaire, the Intrusion subscale (IS) of the Impact of Event Scale; and Selby's QL Uniscale. Fifty-five percent of patients had received medical and/or surgical hormonal therapy, 28% had received a radical prostatectomy and/or radiation therapy only, and 18% had not been placed on any treatment. RESULTS: Patients experiencing problems in adaptation were significantly more likely to have advanced stage disease; received surgical or medical hormonal therapy; and were reporting greater pain, fatigue, urinary problems, and deteriorating physical functioning. Spouses reported significantly greater psychological distress than did patients (EORTC Psychological Distress subscale, P < 0.001; IS, P < 0.001). CONCLUSIONS: A two-stage clinical evaluation is recommended, in which quality of life questionnaires would initially be used to identify patients and spouses experiencing problems in adaptation for further evaluation by a mental health professional for appropriate treatment. PMID- 8194022 TI - A phase I/II study of alternating constant rate infusion floxuridine with constant rate infusion vinblastine for the treatment of metastatic renal cell carcinoma. AB - BACKGROUND: Metastatic renal cell carcinoma (RCC) is largely chemoresistant. The efficacy of cell cycle specific chemotherapeutic agents, particularly those with short half-lives, may be enhanced by the use of constant rate infusion schedules. Infusional floxuridine has been demonstrated to have a response rate of approximately 20%. Infusional vinblastine has not been tested extensively in patients with metastatic RCC. The sequential use of these agents was designed to increase efficacy and limit toxicity. METHODS: Fifteen patients with metastatic RCC were treated with constant rate infusion floxuridine, 0.075 mg/kg/day for 14 days, followed by a constant rate infusion of vinblastine, 0.7 mg/m2/day for 14 days. The cycle repeated every 28 days and floxuridine and vinblastine doses were incrementally increased until the maximum tolerated dose (MTD) for each patient was reached. RESULTS: Four patients had partial responses (27%), which were maintained for 3, 9, 16 and 19+ months, whereas five patients had stable disease for 3-15 months. Median survival from initiation of therapy was 379 days. Three of four responses occurred in nonpulmonary locations, and all responses occurred in patients who had a prior nephrectomy. MTD for floxuridine was 0.1 mg/kg/day and for vinblastine, 0.7 mg/m2/day. Toxic reaction to floxuridine was limited to diarrhea, whereas the principle dose-limiting toxic reaction for vinblastine was neutropenia. Catheter-related complications were also observed. CONCLUSIONS: Alternating constant rate infusion floxuridine and constant rate infusion vinblastine is active in the treatment of metastatic RCC. Whether this regimen is superior to infusional floxuridine is undetermined. Although the toxicity associated with this regimen is manageable, it appears to be more severe than that reported with infusional floxuridine alone. PMID- 8194023 TI - Monoclonal proliferation of double-negative (CD4-CD8-) T-cells bearing T-cell receptor-alpha beta followed by subsequent development of Hodgkin's disease. AB - Expression of CD4 or CD8 on the cell surface is an important guide for discriminating the immunologic functions of T-cells. However, a minor T-cell subset lacking both CD4 and CD8 molecules but bearing the usual form of T-cell receptor (TCR)-alpha beta (CD4-CD8-TCR-alpha beta+ T-cells) has recently been found not only in mice but also in humans, and the clinical relevance of this newly defined subpopulation to human diseases is now of considerable interest. The authors present a patient in whom CD4-CD8-TCR-alpha beta+ T-cells showed monoclonal proliferation in the peripheral blood for more than 3 years, then disappeared spontaneously, followed by subsequent development of Hodgkin's disease. The pathologic roles of double-negative T-cell proliferation in this case are discussed from the viewpoint of premalignancy in lymphoproliferative diseases. PMID- 8194024 TI - Prolonged administration of low dose infusional etoposide in patients with advanced malignancies. A phase I/II study. AB - BACKGROUND: Etoposide displays remarkable schedule dependency. To better define the optimal dose and schedule, the authors administered etoposide as a prolonged low daily dose infusion in patients with a variety of advanced malignancies. METHODS: Between October 1989 and April 1992, 40 patients met inclusion criteria and were enrolled in this study; the initial dose of infusional etoposide was 25 mg/m2/day. Doses were not escalated further, because it became evident that 25 mg/m2/day was the maximum tolerated dose (MTD) in most patients using this prolonged schedule. Because the initial dose proved to be the MTD on this prolonged schedule, several patients received a starting dose of either 20 mg/m2/day or 18 mg/m2/day. This continuous infusion was administered for at least 21 days or until either the leukocyte count dropped to less than 2,000/mm3, platelets dropped to less than 75,000/mm3, or tumor progression occurred. Plasma etoposide levels were obtained at random times during infusions at 25 mg/m2/day. RESULTS: Duration of therapy ranged from 15-561 days. Myelosuppression was the major toxic reaction, although it was mild in most patients and reduced compared with other schedules. Myelosuppression correlated with the extent of prior treatment: minimally pretreated patients tolerated prolonged infusions with only mild hematologic toxic effects, whereas heavily pretreated patients experienced moderate myelosuppression. Patients treated at an initial dose of 25 mg/m2/day had more myelosuppression than did those treated at 20 mg/m2/day. A leukocyte count of less than 1,000/mm3 developed in only 5 of 40 patients (12%) at any time during therapy. Twenty-one patients required packed erythrocyte transfusions, and one required platelet transfusion. The mean serum etoposide concentration in patients receiving 25 mg/m2/day was 0.7 plus or minus 0.42 microgram/ml. Objective responses were obtained in 5 of 10 patients with previously treated non Hodgkin's lymphoma and 2 of 3 patients with previously untreated extensive stage small cell lung cancer. CONCLUSIONS: Etoposide administered by continuous infusion can be given at 25 mg/m2/day for prolonged periods to most patients and is the MTD in previously treated patients. Tumoricidal activity in selected tumor types is demonstrated with this dose. Further study in neoplasms that considered "etoposide-sensitive" seems warranted. PMID- 8194025 TI - Differences in stage at presentation of breast and gynecologic cancers among whites, blacks, and Hispanics. AB - BACKGROUND: One of the possible assumptions for the higher mortality from cancer of blacks versus whites is that blacks tend to be diagnosed relatively more often with later stage disease. This study examined the stages at diagnosis for female breast cancer and other gynecologic cancers among blacks, non-Hispanic whites, and Hispanic whites. METHODS: Data for Dade County were analyzed in this study, which was based on the tumor registry data from the Florida Cancer Data System from 1981-1989. The stages at diagnosis were classified as in situ, local, regional, and distant according to the International Classification of Diseases for Oncology coding rules. RESULTS: The percentage of early stage diagnoses (in situ and local stage) was significantly lower among blacks and Hispanic whites than among non-Hispanic whites, but only for breast and cervical cancer. There was a significant increase in the percentage of early stage diagnoses of breast cancer among all three groups during 1981-1989, whereas this increase was found only in Hispanic whites for cervical cancer. The percentage of in situ cervical cancers was much lower in women older than age 45, especially among women older than age 65, in all three groups. CONCLUSIONS: These data suggest that screening programs need to be targeted differently for specific age and ethnic groups. PMID- 8194026 TI - Plasma thrombospondin levels in patients with gynecologic malignancies. AB - BACKGROUND: Thrombospondin is a high molecular weight glycoprotein, originally described as a secretion product of platelets, that functions as an adhesive protein in cell-cell and cell-substratum interactions. It promotes metastases in the murine model. Plasma thrombospondin has been shown to be elevated in patients with disseminated breast, lung, and gastrointestinal malignancies. METHODS: Blood samples were collected by venipuncture into cubes containing ethylenediamine tetraacetic acid as anticoagulant. They were placed on ice immediately and centrifuged under refrigerated conditions. Plasma was removed and frozen until thrombospondin was quantitated by a competitive enzyme-linked immunosorbent assay. Wilcoxon's two-sample rank-sum test was used to evaluate differences between the patient and control groups. RESULTS: The median plasma thrombospondin level was significantly higher in the patient group compared with the control group, and it was directly correlated with stage of disease. There was no correlation between platelet count and thrombospondin level. CONCLUSIONS: Tumor synthesized thrombospondin could explain the elevated levels in the patent group and also the observation of the correlation between the thrombospondin level and tumor burden. Its function as an adhesive protein may allow it to act as the mediator of metastases. thrombospondin may promote or mediate the metastatic process through its function in cell adhesion. PMID- 8194027 TI - Regression of Kaposi's sarcoma after intravenous immunoglobulin treatment for polymyositis. AB - The authors report on the case of a patient with polymyositis who was given immunosuppressive therapy and then developed Kaposi's sarcoma. Subsequently, the polymyositis was treated with high dose intravenous immunoglobulin, and the Kaposi's sarcoma regressed abruptly. The association between these two diseases and the beneficial effect of intravenous immunoglobulin on Kaposi's sarcoma are discussed. PMID- 8194028 TI - Malignant transformation in a ganglioglioma with anaplastic neuronal and astrocytic components. Report of a case with flow cytometric and cytogenetic analysis. AB - BACKGROUND: Malignant transformation of a ganglioglioma is rare and is generally restricted to the glial component. The authors described a unique case in which neuronal and glial elements exhibited anaplasia in a ganglioglioma. A subtotal resection of a large left temporal tumor extending into the diencephalon and brain stem in a 10-year-old boy revealed a ganglioglioma with no atypical features. The histologic findings were unchanged at further resections 4 and 12 months later. Radiotherapy was instituted with 5500 cGy in 30 fractions 21 months after initial resection. The patient returned 3 years later with a massive midline tumor recurrence. METHODS: The tumor was studied by conventional histologic methods, immunohistochemistry, flow cytometric methods, transmission electron microscopy, immune electron microscopy, and cytogenetic analysis. RESULTS: Although the first three resections revealed a typical ganglioglioma, the fourth resection revealed a cellular pleomorphic tumor with many multinucleated cells and mitoses. The tumor cells expressed glial fibrillary acid protein (GFAP) and synaptophysin on double labeling. By electron microscopy, intermediate filaments, microtubules and abundant rough endoplasmic reticulum, and neurosecretory granules were seen. Immune electron microscopy showed GFAP and synaptophysin within tumor cells. Flow cytometric studies revealed G0G1, 78%; S phase, 9%; and G2M, 13%. Tumor cytogenetics on short term cultures revealed a complex abnormal karyotype with three sublines containing several structural chromosomal abnormalities. CONCLUSIONS: A unique anaplastic transformation of a ganglioglioma is reported with the anaplastic cells exhibiting neuronal and astrocytic features. PMID- 8194029 TI - Dissemination of low grade intracranial astrocytomas in children. AB - The authors report three cases of histologically benign intracranial astrocytomas that developed in children and disseminated within the neuraxis. Multicentric disease was evident at the time of diagnosis in two of these patients, one of whom subsequently developed peritoneal seeding of tumor after placement of a ventriculoperitoneal shunt. To our knowledge, this latter represents the first documented case of extraneural seeding of a benign astrocytoma. All three children are currently alive and well 17-117 months after the diagnosis of tumor dissemination. We review the literature regarding this uncommon problem and discuss the pathophysiology and treatment options. Our results indicate that the presence of disseminated disease may not preclude long term survival, provided the lesions are truly benign histologically and that adjuvant therapy is instituted promptly. PMID- 8194030 TI - The new emphasis of home care. AB - There's been a shift in Vancouver's Home Care program. In the early 1980s, we provided largely "hands on", treatment-oriented care. A physician's order defined the kind and frequency of that care and was a requirement for admission. But in the '90s, all that's changed. The emphasis is on a more holistic approach, on assisting individuals and their families to assume as much control as possible over health-related decisions. A parallel focus is on the growing need for effective and equitable resource allocation. PMID- 8194031 TI - Caring begins at home. AB - The Capital Regional District is the governing body for Victoria and surrounding municipalities. It has been responsible for community health, including home nursing, since 1974. In our publicly funded and operated home nursing care program, registered nurses assess clients and families and provide the services required to promote client health and independence. The nurses' skills are comprehensive: they serve clients of all ages who need acute care; chronic care for an exacerbating short-term episode; intermediate or long term care; or palliative care. PMID- 8194032 TI - Reading, writing and health. AB - In Canada, as in most industrialized nations, the non-communicable chronic diseases--heart disease, cancer and chronic respiratory diseases--remain the leading causes of death and disability. And we know why. Large-scale epidemiological, clinical and laboratory investigations have identified major risk factors associated with the development of chronic diseases. Many of these risk factors, such as a sedentary lifestyle, a high-fat diet and smoking, are the result of habits developed early in life. Therefore, our efforts to prevent chronic diseases must also begin early in life. What better way to reach Canadian children than through our schools? PMID- 8194033 TI - When the going gets tough. AB - How do some nurses hold on to their enthusiasm for work year after year, while others in the same stressful environment grow discouraged, disillusioned and tired of nursing? It could be that some nurses are just plain tougher than others. Hardiness may be the key personality characteristic not just for preventing burnout, but for turning stressful events into meaningful challenges. PMID- 8194034 TI - [Support for parents with anorexic children]. AB - When a diagnosis of anorexia nervosa is reported to parents of older adolescents, those living in the midst of crisis may be unable to follow behavior-change directions demanded by their child's health. At times like this, a support group of parents can complement health professionals' interventions. This article examines a pilot project, based in a large pediatric hospital, that tried to demonstrate the efficacy of such a parent support group. Eight 90-minute weekly meetings were held on four basic themes. And 13 parents made a point of attending them all. Among the benefits: creation of a climate of respect between anorexic adolescents and their parents; increased parental knowledge of anorexia nervosa; and the discovery of new aspects of the parent-child relationship. PMID- 8194036 TI - Charting by exception. PMID- 8194035 TI - [Intercultural care]. AB - Increased immigration into Canada over the last several years has created a country even more culturally diverse than before. And while multiculturalism is beneficial to Canadians, it can also present challenges. One of the main challenges is faced by health professionals daily: that of attempting to meet the various cultural needs of newly arrived immigrants. Essential to the task are relevant knowledge and appropriate attitudes and behavior. Toward these ends, the authors call for an increase in nursing research, and a focus on continuing education and nursing practice information--all relating specifically to multicultural issues. PMID- 8194037 TI - Physiotherapists take stock. PMID- 8194038 TI - Becoming an entrepreneur. PMID- 8194039 TI - Mildred's mission. PMID- 8194040 TI - Identification of chromosomal structural alterations in human ovarian carcinoma cells using combined GTG-banding and repetitive fluorescence in situ hybridization (FISH). AB - In order to identify chromosomal structural alterations in the ovarian carcinoma cell line MLS/P, fluorescence in situ hybridization with centromeric probes for chromosomes 1, 8, 9, 13/21, 14/22, 15, 17, and X and whole chromosome painting probes for chromosomes 1, 3, 4, 5, 7, 8, 9, 10, 12, 13, 14, 17, 19, 22, and X were performed subsequent to GTG-banding. This combined approach identified 14 of the 18 clonal structurally rearranged chromosomes, with the X chromosome involved in three aberrations. In contrast, only eight of the 14 rearrangements were identifiable by G-banding alone. These results indicate that the combined G banding and FISH approach can significantly improve the cytogenetic analysis of human neoplasia. PMID- 8194041 TI - Interphase molecular cytogenetics of Ewing's sarcoma and peripheral neuroepithelioma t(11;22) with flanking and overlapping cosmid probes. AB - The translocation, t(11;22)(q24;q12), recurrently observed in Ewing's sarcoma and in peripheral neuroepithelioma has been recently cloned. The analysis of a series of ES/PNE has revealed that the chromosome 22 breakpoints are clustered in a small region of 7 kb, called EWSR1, and that those on chromosome 11 are spread over a larger region of 40-50 kb, called EWSR2. Cosmids from loci flanking or overlapping these two regions have been obtained. We demonstrate here that fluorescence in situ hybridization (FISH) with these cosmids allows the localization of the two breakpoints with a 10-kb resolution and leads to a rapid and reliable ES/PNE diagnosis. PMID- 8194042 TI - Comparison of chromosome aberrations in leiomyoma and leiomyosarcoma using FISH on archival tissues. AB - Fluorescence in situ hybridization (FISH) with chromosome-specific probes was used to study cytogenetic changes in five cases of leiomyosarcoma (LMS) and nine cases of uterine leiomyoma (LM). Biotinylated DNA probes for the centromeric regions of chromosomes 1, 6, 8, 9, 17, and 18, painting probes for chromosomes 1 and 22, and the cosmid probe for chromosome region 21q22.3 were used on nuclei isolated from paraffin blocks. Four of five LMS cases revealed major chromosomal aberrations, while the only case with minor clonal aberrations was subsequently found not to be a typical LMS. The most common numerical aberrations found in the LMS cases were extra copies of chromosome 8 (three of five cases), loss of chromosome 1 (three of five cases), and loss of chromosome 6 (two of five cases). One of two LMS cases studied with a chromosome 1 painting probe demonstrated translocations of chromosome 1. In contrast to LMS, only five of nine uterine LM cases had abnormal clones, and these were smaller than those in LMS. Two LM cases showed 9% tetrasomy 8 with 17 or 20% monosomy 6, and three other cases had monosomy 6 clones in 18-34% of cells. These results indicate that typical LMS is characterized by multiple chromosomal aberrations affecting most of the cells, whereas borderline LMS and LM have fewer affected chromosomes and less clonal involvement. PMID- 8194044 TI - Cytogenetic abnormalities in two cases of neuroblastoma. AB - Neuroblastomas are common solid tumors in children. We report chromosome analysis of two neuroblastomas, each studied at diagnosis and at recurrence. The first case was a clinical stage D tumor which showed 45,X-Y, add(1)(p34),der(15)t(Y;15)(q11;p13), and double minutes on cytogenetic analysis at diagnosis. At recurrence, the same structural abnormalities were present along with a homogeneously staining region (hsr) at 8q22, 19p12, or 3p23 in each of three related clones. The hsr were shown to represent amplification of the N-myc gene by in situ hybridization. Cytogenetic analysis of the second tumor, stage D S, showed 48-54,XX,der(1)add (1)(q41), +2, +7, +7, inv(9), +17, + mar. The lack of demonstrative involvement of 1p or visible evidence of gene amplification has also characterized the limited number of D-S specimens previously described, suggesting that stage D-S neuroblastoma indeed differs from stage D disease at the genetic level. PMID- 8194043 TI - Cerebral germ cell tumor and XXY karyotype. AB - Metaphases from a cultured cerebral germ cell tumor (CGCT) in a boy with a 46,XY constitutional karyotype had 47 chromosomes with an additional X chromosome and a translocation (1;21)(q11;p11). CGCT appear to be nonrandomly associated with Klinefelter syndrome, and a supernumerary X chromosome and trisomy of the 1q21- >1qter region may be clonal abnormalities in these tumors. The predisposition of Klinefelter patients to develop CGCT may be due to the pathogenetic relevance of the extra X chromosome both as an acquired and a constitutional abnormality. PMID- 8194045 TI - Unbalanced 1;7 translocation in myelodysplastic syndrome following treatment of acute myeloblastic leukemia with an 8;21 translocation. AB - The chromosome der(1;7)(q10;p10) consists of the short arm of chromosome 7 and the long arm of chromosome 1, and is a common abnormality in treatment-related leukemia and myelodysplastic syndrome. Here we describe a 39-year-old Japanese man with acute myeloblastic leukemia (FAB-M2) exhibiting t(8;21)(q22;q22). He entered complete remission after induction therapy, and intensification therapy including alkylating agents was subsequently continued for 3 years. The patient then developed pancytopenia; bone marrow aspiration revealed myelodysplastic syndrome exhibiting the der (1;7) chromosome. To our knowledge, this is the first reported case of such an abnormality in myelodysplastic syndrome secondary to acute myeloblastic leukemia with the 8;21 translocation. PMID- 8194046 TI - Cytogenetic studies, ras mutation, and clinical characteristics in primary myelodysplastic syndrome. A study on 68 Chinese patients in Taiwan. AB - Cytogenetics and clinical features were studied for 68 Chinese patients with primary myelodysplastic syndrome (MDS). Ras mutation was analyzed in 25 of them. Thirty-four patients (50%) had clonal chromosomal abnormalities at initial analysis. The most common cytogenetic aberrations were -7, +8, 5q-, and 20q-, which occurred in 11 (16.2%), seven (10.3%), five (7.4%) and three patients, respectively. The incidence of -7 was higher and that of 5q- lower in our patients than in patients from most other geographic areas. The 17 patients with multiple chromosomal abnormalities had a significantly shorter median survival (9 months) than the 34 patients with normal karyotype (33 months) and the 17 patients with patients with single anomalies (26 months). Evolution to acute leukemia occurred in 20 patients (29%) after a median interval of 8 months following the diagnosis. Patients with multiple cytogenetic changes at initial analysis or in subsequent studies had a significantly higher frequency of acute transformation than others (55% vs. 18.6%, p = 0.007); the same was not true if only the data of initial study were considered. Serial cytogenetic studies are important in patient follow-up. N-ras mutation was detected in 5 (20%) of 25 patients within the study. There was no correlation between the gene mutation and acute transformation. But combing the data of N-ras mutation and cytogenetics, patients with either the N-ras mutation or clonal chromosomal abnormalities were at significantly higher risk for developing acute leukemia than those with neither of the changes (77% vs. 25%). PMID- 8194048 TI - Cytogenetics and origins of pediatric germ cell tumors. AB - We present cytogenetic and DNA fingerprint analysis on 13 new cases of pediatric germ cell tumors; we analyze further four cases we have reported previously. The patients ranged in age from 23 weeks gestation to 16 years. The tumors were located in the ovary, sacrococcygeum, testis, mediastinum, and the craniofacial region, and represented benign, immature, and malignant cases. All of the new cases had a normal diploid karyotype. We have previously reported on multiple genetic mechanisms of origin for ovarian germ cell tumors, namely meiosis I nondisjunction, meiosis II nondisjunction, endoreduplication of a haploid ovum, mitotic division of premeiotic germ cell, and fusion of two ova. To determine the origin of extragonadal and testicular GCTs, Q-band centromeric heteromorphisms and DNA markers were analyzed in the host and the cognate tumor. Our data suggest that extragonadal and testicular GCTs do not arise by a meiosis I or II error, or by endoreduplication; rather, they arise mitotically from either a somatic or a germ cell. PMID- 8194047 TI - A case of acute monocytic leukemia with t(11;17) involving a rearrangement of MLL 1 and a region proximal to the RARA gene. AB - A case of acute monocytic leukemia with t(11;17)(123;q11-21) arising in a 4-month old boy is described. The breakpoint on chromosome 11 could be mapped to an 8-kb BamHI fragment within the MLL-1 gene, as seen in the majority of infant leukemias. In situ hybridization with cosmid probes allowed us to map the breakpoint on 17q proximal to the RARA gene, while Southern and Northern analyses showed that the gene was not disrupted by the translocation. PMID- 8194049 TI - Granulocytic sarcoma showing chromosomal changes other than the t(8;21). AB - Cytogenetic analysis of a granulocytic sarcoma showed a 46,XX,der(X)t(X;1) (q28;q22), inv(3)(p21q27), inv(9)(p13q22),t(12;22)(p11;q11) karyotype. In addition, bone marrow aspirate disclosed the presence of cells with a 46,XX,inv(3)(p21q27),inv(9)(p13q22)(p11;q11) chromosomal pattern while the patient was clinically aleukemic. This case demonstrates that chromosomal abnormalities other than the classical t(8;21) can also be associated with granulocytic sarcoma. PMID- 8194050 TI - Trisomy 19 as the sole chromosomal anomaly in hematologic neoplasms. AB - Trisomy 19 was found as the sole chromosomal aberration in three hematologic malignancies: one chronic myelomonocytic leukemia and two cases of of immunophenotypically immature acute myeloid leukemia (AML). A compilation of previously published hematologic neoplasms with +19 as the only change reveals that this anomaly is strongly associated with myeloid malignancies; 25 of 31 cases have been myelodysplastic syndromes (MDS) or AML. Eight of the 11 MDS cases have been either refractory anemia (RA) or RA with excess of blasts, and four of the 14 AML cases have had preleukemic myelodysplastic cases phase, with the +19 accruing during the time of leukemic transformation. The AML cases have, in general, been either or early maturation arrest, i.e. undifferentiated or AML M1/M2, or of myelomonocytic-monoblastic origin, i.e., AML-M4/M5. None of the MDS or AML cases with +19 had had a previous history of radio- or chemotherapy. We conclude that trisomy 19, as the sole anomaly, is a characteristic abnormality in de novo myeloid malignancies. No clinical features seem to characterize patients with +19 AML and MDS and the prognostic impact of the aberration remains to be elucidated. PMID- 8194051 TI - Tetrasomy 21 in megakaryoblastic leukemia. AB - A 23-month-old female evaluated for profound anemia proved to have megakaryoblastic leukemia. The diagnosis is based on examination of bone marrow morphology, cytochemical characteristics, and immunophenotype. The chromosome complement of unstimulated blast cells in peripheral blood and bone marrow was 48,XX,+21,+21. Tetrasomy 21 is the sole clonal cytogenetic abnormality in this patient with megakaryoblastic leukemia. The constitutional complement of the patient is normal female, 46,XX. PMID- 8194052 TI - Trisomy 14 in a case of sideroblastic refractory anemia. PMID- 8194053 TI - Spontaneous expression of the chromosome fragile site at 10q23 in leiomyoma. PMID- 8194054 TI - 5q- chromosome. Evidence for complex interstitial breaks in a case of refractory anemia with excess blasts. AB - Interstitial loss of the long arm of chromosome 5 (5q-) is an anomaly frequently seen in myelodysplasia (MDS) and acute myelogenous leukemia (AML). Although the limits of the interstitial deletions vary among patients, there is a critical region of overlap at 5q31 that is consistently deleted in most cases. The order of genes in the critical 5q31 region is centromere, interleukin gene cluster, an anonymous polymorphic locus D5S89, early growth response factor, CSF1 receptor, telomere. Fluorescence in situ hybridization of specific 5q31 probes to metaphases with del(5) (q11q31) from a patient with secondary refractory anemia with excess blasts in transformation demonstrates that the interstitial deletion is not contiguous. The 5q- chromosome has lost the D5S89 and CSF1R loci while retaining some of the sequences in between. A probe derived from a 300-kbp yeast artificial chromosome containing the D5S89 locus is interrupted on the normal chromosome 5 of this patient. Data presented in this report are consistent with (i) presence of a critical gene within the YAC and (ii) more than a single interstitial break within the 5q- chromosome. These results, while pinpointing one of the critical 5q31 loci, also provide evidence for a second telomeric locus. PMID- 8194055 TI - Consensus conference: Hydrocephalus '92. Assisi, Italy, 26-30 April 1992. PMID- 8194056 TI - The usefulness of mathematical modeling in hydrocephalus research. AB - A mathematical model of the regulation of ventricular volume, which emphasizes the importance of the intrinsic properties (turgor) of the brain for the understanding of hydrocephalus, has been developed. How the model was generated is described. The use of the model for understanding the various forms of hydrocephalus is discussed. Finally, the usefulness of the model in solving difficult clinical problems, such as diffuse pediatric head injury and progressive ventriculomegaly with low intracranial pressure, is described. PMID- 8194057 TI - Early ventriculoperitoneal shunt--effects on learning ability and synaptogenesis of the brain in congenitally hydrocephalic HTX rats. AB - The learning ability of congenitally hydrocephalic HTX rats in which hydrocephalus had been arrested by the insertion of a V-P shunt 7 days after birth (early shunt) was assessed by means of the light-darkness discrimination test when the animals reached maturity. Early shunt placement resulted in marked reduction in size of abnormally enlarged ventricles and the prevention of both decreasing spine density and decay of synaptic vesicle protein (SVP-38) in the affected cerebral cortex. The learning ability of such animals was also found not to be impaired compared with that of animals in a sham-operation group. On the basis of these investigations, it is concluded that early shunt placement may have a beneficial role in preventing not only impairment of synaptogenesis of the brain by progressing hydrocephalus, but also learning disability. Recent biochemical investigation of the developing brains of hydrocephalic HTX rats revealed problems that cannot be resolved by early shunt insertion, and these are also discussed. PMID- 8194058 TI - A unifying theory for the definition and classification of hydrocephalus. AB - If the cerebrospinal fluid (CSF) is considered to be all the fluid (liquid), other than blood or the derivatives of its breakdown, that is normally contained within the brain, its cavities, and its spaces, this could be regarded as "brain fluid" in its most elemental form. "Pathological increases in intracranial CSF volume, independent of hydrostatic or barometric pressure", then, could be considered a definition of hydrocephalus. The observation of significant episodic variation in intracranial pressure (ICP) suggests the necessity of substituting the concept of "time-related pressure variations" for the older one of "level of pressure" in patients with defective ICP control mechanisms. It has been assumed that the subarachnoid channels are the first CSF compartment to dilate in response to the hydrocephalic process, reducing the CSF pressure and thereby establishing an equilibrium. When the equilibrium is disturbed, with progressive dilation of the subarachnoid channels, the increase in CSF pressure is transmitted to the ventricular system, resulting in its dilation (extraprenchymal hydrocephalus). Progressive ventricular dilation causes cerebral edema (intraparenchymal hydrocephalus) and obliterates the subarachnoid spaces as the hemispheres are compressed against the dura, resulting in apparent "internal hydrocephalus" in the absence of "external hydrocephalus". Thus, subarachnoid space or ventricular dilation occur as a result of intermittent increases in extraparenchymal CSF volume: the primary pressure force emanating from the subarachnoid and subdural spaces and from the intraventricular compartment. Hydrocephalus, therefore, may be present in a child who does not yet have dilated ventricles but in whom both CSF volume and pressure are increased. Thus, it becomes obvious that the term internal hydrocephalus is of little significance, since increases in intraparenchymal fluid--cerebral edema--cause the same volumetric changes as increases in intraventricular fluid volume. I suggest that hydrocephalus is a pathologic increase in intracranial CSF ("brain fluid") volume, whether intra- or extraparenchymal, independent of hydrostatic or barometric pressure. It may be classified as (1) intraparenchymal (cerebral edema) and (2) extraparenchymal, with the extraparenchymal types subclassified into subarachnoid, cisternal, and intraventricular forms. PMID- 8194059 TI - Consensus: modelling of hydrocephalus. PMID- 8194060 TI - The relationship of intracranial venous pressure to hydrocephalus. AB - Little is known about intracranial venous pressure in hydrocephalus. Recently, we reported that naturally occurring hydrocephalus in Beagle dogs was associated with an elevation in cortical venous pressure. We proposed that the normal pathway for cerebrospinal fluid (CSF) absorption includes transcapillary or transvenular absorption of CSF from the interstitial space and that the increase in cortical venous pressure is an initial event resulting in decreased absorption and subsequent hydrocephalus. Further analysis, however, suggests that increased cortical venous pressure reflects the effect of the failure of transvillus absorption with increase in CSF pressure on the venous pressure gradient between ventricle and cortex. Normally, the cortical venous pressure is maintained above CSF pressure by the Starling resistor effect of the lateral lacunae. A similar mechanism is absent in the deep venous system, and thus the pressure in the deep veins is similar to that in the dural sinuses. Decreased CSF absorption causes an increase in CSF pressure followed by an increase in cortical venous pressure without a similar increase in periventricular venous pressure. The periventricular CSF to venous (transparenchymal) pressure (TPP) gradient increases. In contrast, cortical vein pressure remains greater than CSF pressure (negative TPP). The elevated periventricular TPP gradient causes ventricular dilatation and decreased periventricular cerebral blood flow (CBF), a condition that persists even if the CSF pressure returns to normal, particularly if tissue elastance is lessened by tissue damage. If deep CBF is to be maintained, periventricular venous pressure must increase. Since the veins are in a continuum, cortical venous pressure will further increase above the CSF pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194061 TI - Valvular factors in hydrocephalus. AB - Various ways in which blockage of cerebrospinal fluid pathways can lead to increasing intracranial pressure and enlargement of the ventricles are discussed. The necessity of understanding the valvular morphology involved is stressed as fundamental to the search for optimal treatment methods. PMID- 8194062 TI - Hydrocephalus: the zero ICP ventricle shunt (ZIPS) to control gravity shunt flow. A clinical study in 56 patients. AB - Significant morbidity from ventricle shunt overdrainage at 6-7 years after initial shunt placement for hydrocephalus is increasingly recognized as due to excessive gravity-flow of shunted CSF when upright. Shunts are designed primarily to control high ICP. Shunts should also mimic normal upright ICP. Normal upright ICP is -65 mm of water (vertex reference), indicating that a level of zero ICP exists at 65 mm below the brain vertex, with negative ICP above and positive ICP below that level. This normal zero ICP level must be maintained by CSF shunts to mimic normal upright ICP. This will prevent and correct CSF shunt overdrainage. The zero ICP shunt (ZIPS) by design controls this zero level with a zero pressure device (ZPD; siphon control device) installed at the normal vertical level of zero ICP (cm/mm) below the vertex (65 mm). The shunt thus prevents excessive gravity-induced CSF shunt flow. Successful use of ZIPS in 56 patients is reported (low ICP group: n = 42; high ICP group: n = 14). Follow-up is up to 4.5 years. Results show that: (1) adjustability of ZPD level can achieve the desired clinical results; (2) the level of ZPD installed correlates within 4 mm of upright ICP attained; (3) the optimal level of ZPD installation to produce normal upright ICP is 65 mm below the vertex; (4) CT ventricle size, both slit ventricles and large ventricles, may or may not normalize when normal upright ICP is attained in this group of complex, previously shunted patients. PMID- 8194063 TI - Is the slit ventricle syndrome always a slit ventricle syndrome? AB - The term 'slit ventricle syndrome' (SVS) refers to the occurrence of headache, vomiting, and possibly some degree of consciousness impairment in shunted hydrocephalic children in whom slit-like ventricles are seen on computerized tomography (CT) scan examination. The syndrome has been typically observed in older hydrocephalic children operated on in early infancy, even though it has also been observed occasionally in young children and adults. The clinical characteristics of the SVS, the results of the laboratory investigations and the therapeutic measures utilized in the various cases described in the literature differ so widely as to suggest that different clinical conditions are actually being described. In some cases, the diagnosis of SVS should be avoided and substituted by a correct diagnosis of CSF shunt malfunction or of disturbances unrelated to the CSF shunting therapy, e.g., childhood migraine. PMID- 8194064 TI - Silicone allergy in ventriculoperitoneal shunts. AB - Reported are the cases of three hydrocephalic patients who developed a clinically heterogenous entity with an allergic rejection of their silicone ventriculoperitoneal shunts. All of the patients had an original presentation indicative of a shunt infection, but laboratory analysis revealed sterile cerebrospinal fluid in all three cases. The typical course included recurrent skin breakdowns over the shunt tract, subsequent infections and development of fungating granulomas. Treatment, with successful resolution of the symptoms, included changing the shunt material from silicone to polyurethane, with immunosuppression in one patient and removal of the shunt altogether in the other two patients. The roles of the immune system and silicone in the pathophysiology of this condition are discussed. PMID- 8194065 TI - Consensus: long-term outcome in hydrocephalus. AB - Developments in the treatment of hydrocephalus and its outcome are traced from the time of Hippocrates up to the present day. Various factors that have been suspected of influencing the outcome are discussed and their relative importance for long-term outcome is reviewed. PMID- 8194066 TI - Intelligence outcome in children with shunted hydrocephalus of different etiology. AB - Children with shunted hydrocephalus of differing etiologies were assessed. There was a more selective loss of non-verbal than of verbal intelligence. The verbal and visuo-perceptual abilities were affected by different sets of variables. Variables related to the hydrocephalus had no effects, while associated supratentorial malformations significantly affected non-verbal functions. PMID- 8194067 TI - Identification of a novel sugar, 4-amino-4,6-dideoxy-2-O-methylmannose in the lipopolysaccharide of Vibrio cholerae O1 serotype Ogawa. AB - A novel sugar in the lipopolysaccharide of Vibrio cholerae O1 serotype Ogawa has been identified. The sugar was liberated from the lipopolysaccharide when hydrolyzed in 10 M HCl at 90 degrees C for 15 min. The sugar was purified and identified as 4-amino-4,6-dideoxy-2-O-methylmannose (2-O-methylperosamine). Since it was found only in the lipopolysaccharide of Vibrio cholerae O1 serotype Ogawa, it seems that the sugar is one of the specific constituents determining Ogawa serotype specificity. PMID- 8194068 TI - Inhibition of amylopectin retrogradation by partial beta-amylolysis. AB - The rate of retrogradation of amylopectin solution differs from one starch variety to another and it is thought to be due to the different length of the external chains of amylopectin. A shortening of the external chains of waxy maize and potato amylopectin was performed with beta-amylase. Partial beta-amylolysis produced a significant fraction of chains having 2-6 glucose units. A high linear correlation (R > 0.97) was found between the enthalpy of retrograded amylopectin measured by DSC, or percent solid measured by low frequency pulsed NMR, and average external chain length. No retrogradation appeared to occur when the external chains of both amylopectins had 11 or less glucose units on average. The inhibition of retrogradation appears to be caused primarily by the presence of very short external chains, which hinders the reassociation of the long external chains. PMID- 8194069 TI - Binding geometry, stoichiometry, and thermodynamics of cyclomalto-oligosaccharide (cyclodextrin) inclusion complex formation with chlorogenic acid, the major substrate of apple polyphenol oxidase. AB - The inclusion complexes of cyclomaltohexaose (alpha-CD), cyclomaltoheptaose (beta CD), cyclomaltooctaose (gamma-CD), and polymerized beta-CD (beta-CDn) with chlorogenic acid (CA), the major substrate of apple fruit polyphenol oxidase (PPO), were studied with regard to pH, ionic strength, and temperature in model buffer systems and apple juice. The thermodynamics of CD.CA inclusion complex formation, which were studied in solution using UV spectrophotometry, displayed enthalpy-entropy compensation typical of processes driven by solvation phenomena. We also found that the apparent association constants (K) of the CD.CA equilibrium were relatively insensitive to pH for beta-CD, compared to alpha- and gamma-CDs, but were subject to substantial enhancement at low ionic strengths. The beta-CD.CA inclusion complex was also characterized for binding geometry and stoichiometry at 9.4 T and 25 degrees C in 0.05 M Na phosphate buffer by 1H NMR spectroscopy. A 1:1 stoichiometric ratio for the complex was found using the method of continuous variations. 1H Spin-lattice relaxation and chemical-shift data indicate that the phenolic ring of CA docks within the cavity of beta-CD. The Ks for beta-, alpha-, and gamma-CD determined in apple juice, which contains a mixture of PPO substrates, were found to correlate with PPO activity-related data. Apple juice, treated with beta-CDn, did not brown until CA was added back. These latter findings strongly argue that the mechanism for inhibition of juice browning with cyclodextrins was mainly due to the binding of PPO substrates and not some other means such as enzyme inactivation via sequestration of Cu2+ by CDs. PMID- 8194070 TI - Differing patterns of carbohydrate metabolism in liver and muscle. AB - The effect of a period of starvation followed by refeeding on skeletal muscle glycogen was investigated by the use of double-labelled radioactive glucose precursors in rats. Skeletal muscle glycogen, which is not depleted to anything like the extent of liver glycogen, shows a remarkable stability with respect to its overall molecular size distribution during starvation and subsequent refeeding. The experiments also indicate that there is a control mechanism in muscle tissue enabling the synthesis of lysosomal glycogen to be switched off during the initial part of the refeeding process. The results emphasise the inadequacy of the Cori cycle and a modified version is proposed. PMID- 8194071 TI - Novel structures of N-linked high-mannose type oligosaccharides containing alpha D-galactofuranosyl linkages in Aspergillus niger alpha-D-glucosidase. AB - Seven oligosaccharides were isolated from alpha-D-glucosidase (EC 3.2.1.20) from Aspergillus niger, and the structures of these oligosaccharides were studied by 1H NMR spectroscopy. After treatment of the alpha-D-glucosidase with N glycosidase F, seven major oligosaccharide peaks were detected by Dionex anion exchange HPLC. The structures corresponding to the three peaks OS-1, OS-2, and OS 4 were determined to be Man8GlcNAc2, Man9GlcNAc2, and GlcMan9GlcNAc2, respectively, from 1H NMR spectra of the isolated fractions. Each of the four oligosaccharides OS-5, OS-6, OS-7-1, and OS-7-2 contained an alpha-D galactofuranosyl residue (Galf) linked to Man(A) via an alpha-(1-->2)-linkage. OS 7 was found to consist of two oligosaccharides. The structures of these four oligosaccharides were determined to be GalfMan5GlcNAc2, GalfMan6GlcNAc2, GalfMan7GlcNAc2, and GalfMan8GlcNAc2 by 1H NMR spectroscopy and compositional analysis. The Galf structure of GalfMan5GlcNAc2 was found to be identical to that of an oligosaccharide previously isolated from the alpha-D-galactosidase of the same strain. The structure of OS-3 remains undetermined. PMID- 8194073 TI - In vitro reducing abilities towards chromate of various hydroxy-containing compounds, including saccharides and their derivatives. AB - The reduction of potassium chromate has been carried out with a variety of OH containing compounds as reductants, which include pentoses, polyols, glycols, and sugar derivatives. The corresponding reactions were followed using UV-vis and EPR spectroscopies and electrochemistry. The progress of the chromate reduction reactions has been monitored by measuring UV-vis and EPR spectra as a function of time. The observed pseudo first-order reaction rate constants are derived based on the changes in the intensities of the Cr(VI), Cr(V), and Cr(III) signals. Cyclic voltammograms of the simple reductants and their final Cr(III) products formed from the reactions of chromate have also been measured. The reductive abilities of all these reductants have been derived from the spectral data and are discussed on a comparative basis. Based on the results, the aspects that makes a particular reductant more efficient has been addressed. The results obtained from UV-vis, EPR, and cyclic voltammetry are found to be mutually dependent and exhibit among themselves a linear correlation, suggesting that both the reducing and complexing nature of these molecules play important roles in the chromate reduction. PMID- 8194072 TI - Synthesis of 2-fluoroethyl beta-D-galactopyranoside and 2-fluoroethyl 6-O-beta-D galactopyranosyl-beta-D-galactopyranoside from lactose using beta-D galactosidase. PMID- 8194074 TI - The degradation of L-threose at Maillard reaction conditions. AB - L-Threose, a comparatively unstable aldose, is produced from L-ascorbic acid in the presence of oxygen and participates vigorously in Maillard reactions, even at comparatively mild conditions. In the present study, the degradation of L-threose at pH 7.0 alone, in the presence of N-alpha-acetyl-L-lysine, and at pH 2.0 alone at 37 degrees C was investigated by identification of some of the products produced in the reactions by means of GLC and GLC-MS. Among the compounds identified were 3-deoxy-tetros-2-ulose (1), the predicted alkaline rearrangement product derived from 1 (2,4-dihydroxybutyrate, the 4-carbon metasaccharinic acid), as well as glyceraldehyde. Isotopic tracer studies clearly show that the glyceraldehyde is produced by loss of C-1 from the starting L-threose molecule. The presence of N-acetyl lysine in incubation solutions appears to accelerate the production of 1, but the formation of glyceraldehyde appears to be independent of the lysine derivative. PMID- 8194075 TI - A chemoenzymatic synthesis of D-myo-inositol 1,4,5-trisphosphate. AB - Enzyme-catalyzed esterification of racemic 2,3-O-cyclohexylidene-myo-inositol (DL 1) proceeded exclusively in 1,4-dioxane to give optically pure L-1-O-acetyl-2,3-O cyclohexylidene-myo-inositol (L-2) and D-2,3-O-cyclohexylidene-myo-inositol (D 1). A new practical route has been developed for the synthesis of D-myo-inositol 1,4,5-trisphosphate starting from D-1 via selective acylation of the 6-hydroxyl group. PMID- 8194076 TI - Synthesis of a glycopeptide with phytoalexin elicitor activity. I. Synthesis of a triglycosyl L-serine and a triglycosyl L-seryl-L-proline dipeptide. AB - A stereocontrolled synthesis of the model compound for the phytoalexin elicitor active glycoprotein is described. Glycosylation of the disaccharide, 2,3,4,6 tetra-O-acetyl-beta-D-glucopyranosyl-(1-->6)-2,3,4-tri-O-acetyl- alpha- D mannopyranosyl trichloroacetimidate, with N-(carbobenzoxy)-(2,3,4-tri-O-acetyl alpha-D-mannopyranosyl)-(1-->3)-L- serine methyl ester or N-(carbobenzoxy)-(2,3,4 tri-O-acetyl-alpha-D-mannopyranosyl)-(1-->3)-L- seryl-L- proline methyl ester by use of AgOTf gave the desired trisaccharide-serine or trisaccharide-seryl-proline derivatives, which were transformed into beta-D-glucopyranosyl-(1-->6)-alpha-D mannopyranosyl-(1-->6)-alpha-D- mannopyranosyl-(1-->3)-L-serine and triglycosyl (1-->3)-L-seryl-L-proline via removal of the N-carbobenzoxy group, followed by deacylation. PMID- 8194077 TI - Isolation and characterization of rhamnogalacturonan oligomers, liberated during degradation of pectic hairy regions by rhamnogalacturonase. AB - Digests of modified hairy regions of apple pectin (MHR) obtained after degradation by rhamnogalacturonase (RGase) were analyzed for oligomer composition using high-performance anion-exchange chromatography and pulsed amperometric detection. A series of oligomers which appear to be characteristic of RGase degradation could be recognized. These oligomers were isolated on a preparative scale by size-exclusion chromatography and preparative anion-exchange chromatography and analyzed for sugar composition. 1H NMR spectroscopy showed that the oligomers consisted of between 4 and 9 sugar units with a backbone of alternating rhamnose and galacturonic acid residues, partly substituted with galactose residues linked to C-4 of the rhamnose moiety. The HPLC elution pattern showed that higher oligomers were also formed during incubation with RGase. These have the same basic structure but may contain other sugar units in addition to those given above. The oligomer composition of RGase digests of MHR isolated from apple, pear, leek, onion, carrot, and potato was very similar. Using anion exchange chromatography to monitor the degradation of MHR at increasing incubation times, it was found that all the oligomers were present from the initial stages of the enzyme reaction and that the ratio between the different oligomers remained constant with time. Implications of these results for the structure of MHR and the mechanism of RGase action are discussed. PMID- 8194079 TI - Ca(2+)-dependent K+ channel activity in rat glioma cells induced by bradykinin stimulation and by inositol 1,4,5-trisphosphate injection. AB - 1. A glial cell line derived from C6 rat glioma cells has been shown previously to respond to extracellular pulses of bradykinin or intracellular injection of inositol 1,4,5-trisphosphate (Ins-P3) with a slow hyperpolarizing response due to activation of a K+ current (G. Reiser et al., Brain Res. 506, 205-214; 1990). 2. We determined the ensuing single-channel activity, which is most likely caused by Ca2+ released from internal stores after bradykinin stimulation. Bradykinin activated channels were selectively permeable to K+, but not to Na+ or to Cl-, and exhibited conductances of mainly 40 and 50 pS. In glioma cells the same type of channel was activated by intracellular injection of Ins-P3 and by extracellular bradykinin pulses. PMID- 8194078 TI - The stress-induced reduction in monoamine oxidase (MAO) A activity is reversed by benzodiazepines: role of peripheral benzodiazepine receptors. AB - 1. The effect of benzodiazepine pretreatment on the stress-induced decrease in MAO activity in rat tissues using footshock as stress model was investigated. 2. Animals were injected with vehicle, Lorazepam (1.25 mg/kg), or Clonazepam (0.5 mg/kg) 2 hr before or with PK 11195 (0.45 mg/kg) 2.5 hr before being subjected to one session of 10 inescapable footshocks or to a sham session. At the end of the session animals were sacrificed and MAO A and B activities in hearts and brains were determined. 3. Pretreatment of the animals with both Lorazepam and Clonazepam abolished the decrease induced by footshock in MAO A activity in brain. Pretreatment with Lorazepam but not with Clonazepam abolished the stress induced decrease in MAO A in the heart. Pretreatment with PK 11195 before Lorazepam reversed its effects in the heart but not in the brain. Neither footshock nor any of the drugs used had any effect on heart and brain MAO B. 4. Our results suggest that in the heart but not in the brain, peripheral benzodiazepine receptors play a role in the regulation of MAO A activity under stress conditions. PMID- 8194080 TI - Differential effects of cytoskeletal agents on hemispheric functional expression of cell membrane receptors in Xenopus oocytes. AB - 1. We studied the effects of three cytoskeleton-disrupting agents, colchicine (COL), vinblastine (VIN), cytochalasins, on the functional hemispheric expression of native muscarinic and acquired thyrotropin-releasing hormone receptors TRH Rs). Responses in oocytes of common donors, which express M3-like receptors (M3Rs), were not affected by either COL or VIN on the animal hemisphere. The functional expression of M3Rs on the vegetal hemisphere was inhibited by 50%. Cytochalasin B caused a uniform inhibition (by 31-33%) of receptor functional expression on either hemisphere. 2. Oocytes of variant donors express predominantly M1-like receptors (M1Rs) on the animal and M3Rs on the vegetal hemisphere. In these oocytes, both COL and VIN caused approximately 50% inhibition of functional expression on either hemisphere. Cytochalasin B caused more extensive, though variable inhibition on both hemispheres. Both antitubulin agents had no effect on the functional expression of the TRH-Rs on either hemisphere. Cytochalasin B, however, caused an extensive inhibition of the functional expression of this receptor (by 70-75%). 3. Induction of maturation of oocytes (7-hr incubation with progesterone) resulted in a 66% decrease in the response to TRH, reflecting mainly a decrease on the animal hemisphere. Maturation in the presence of colchicine had no further effect on the activity measured on the animal hemisphere but caused a major increase in the activity on the vegetal hemisphere. This resulted in a dramatic change in animal/vegetal activity ratio (4.8 +/- 1.5 to 0.8 +/- 0.2). 4. It appears that while antitubulin drugs affect the functional expression of the three receptors at the two hemispheres differently, disruption of the microfilaments interferes uniformly with receptor functional expression. We suggest that microfilaments may be involved in a common component of the signal transduction pathway in oocytes or in the anchoring of receptors coupled to the guaninine nucleotide-binding regulatory proteins. Moreover, progesterone-induced changes in the functional organization of the signal transduction pathway appear to be controlled to a large extent by the tubulin component of the cytoskeleton. PMID- 8194081 TI - Protein kinase C and clostridial neurotoxins affect discrete and related steps in the secretory pathway. AB - 1. The effects on catecholamine secretion of activation of protein kinase C and clostridial neurotoxins were examined in digitonin-permeabilized bovine adrenal chromaffin cells. 2. The enhancement by phorbol esters increased only the initial rate of secretion; later rates were unaffected. This enhancement was present over a wide range of Ca2+ concentrations and was elicited at 18 as well as at 27 degrees C. 3. Tetanus toxin inhibited both ATP-dependent and ATP-independent secretion, indicating that the tetanus toxin target is important during the final steps in the pathway. 4. Prior activation of protein kinase C by the phorbol ester 12-O-tetradecanoyl phorbol acetate rendered the primed state more sensitive to inhibition by tetanus toxin. The data indicate that a phosphorylated protein kinase C substrate is either identical to or closely associated with the tetanus toxin target protein at the final steps in the pathway. 5. The interaction between the effect of protein kinase activation and that of tetanus toxin suggests that protein kinase C activation does not stimulate a separate pathway of secretion but, rather, modulates the activity of the ongoing pathway. 6. The enhancement of secretion by protein kinase C is caused, at least in part, by a qualitative change in the characteristics of the primed state. This is indicated by the increased sensitivity of primed secretion to inhibition by tetanus toxin and a threefold increase in sensitivity of primed secretion to Ca2+. 7. Because activation of protein kinase C does not increase the later rates of secretion that are limited by ATP-dependent priming reactions, it is unlikely that enhancement of the maximal rate of secretion by TPA is due to an increased amount of the primed state. Instead, protein kinase C activation may increase the efficacy with which Ca2+ stimulates secretion at all Ca2+ concentrations. PMID- 8194082 TI - Biphasic effects of suramin on 125I-epidermal growth factor binding to human meningiomas. AB - 1. We studied the effects of suramin, a nonspecific growth factor antagonist, on epidermal growth factor (EGF) binding to cell surface receptors in surgically excised human meningiomas, using quantitative receptor autoradiographic methods with radioluminography. 2. High concentrations (10(-4) - 10(-2) M) of suramin inhibited 125I-EGF binding to meningioma sections with IC50's of 3.2 +/- 0.4 x 10(-4) M, whereas lower concentrations (10(-5) - 10(-4) M) of the drug significantly enhanced EGF binding to the tumor. Scatchard analysis of EGF binding profile revealed significant increases in binding affinity following incubation in the presence of 5 x 10(-5) M suramin, without significant alterations in maximal binding capacity. 3. The addition of 10(-3) M suramin to the incubation buffer rapidly dissociated 125I-EGF previously bound to meningioma tissues as a function of time (dissociation half-life, T1/2 = 12.4 min). 4. Preincubation in the presence of 5 x 10(-5) M suramin resulted in significant increases in the subsequent binding of 125I-EGF to meningiomas, compared to findings in the control. 5. Our data indicate that (a) suramin exerts biphasic effects on EGF binding to the tissue sections of meningiomas in vitro, depending on the concentration of the drug; and (b) low concentrations of suramin enhance the affinity of the EGF receptor in the tumor sections, probably by interacting with the EGF receptor molecule rather than with the EGF peptide. 6. The functional role of increased EGF receptor affinity in meningioma sections in the presence of lower concentrations of suramin remains to be determined. PMID- 8194084 TI - [Specific reading disorders and the neurobiology of speech]. AB - Overview of views on dyslexia-specific reading disorders. The most important contribution to the problem was the work of S. T. Orton which began more than 60 years ago. He was the first to formulate the neuropsychological theory of dyslexia. His followers use as a basis his idea that the specific background of dyslexia are cerebral mechanisms with decisive functional relations of the two cerebral hemispheres, but they abandon the factor of dominance of one half of the cerebral cortex. An important contribution was the work of D. Kimura et al. (some 30 years ago) who published findings relating to the role of the hemispheres in processing different grades of human speech, spatial, superficial and figural stimuli (inc. text). During the last twenty years interesting findings were provided by child neurologists R. Masland, N. Geschwind and his pupil and follower A. Galaburda (cytoarchitectonic investigations of the brain) and the neurosurgical clinic of Prof. G. A. Ojeman. Thus a new discipline was developed- neurobiology of speech as well as other branches of so-called neurosciences. Their findings will influence in future not only the approach to handicapped children but also the organization of the training process and teaching methods. PMID- 8194086 TI - [Endocrinology 1992-1993]. AB - In a brief review of advances made in endocrinology during the past two years, focused on steroid hormones, the author discusses findings on mineral corticoid and glucocorticoid receptors and their interaction with hormone responsive elements in nuclei of target cells. The antimicrobial action of some steroid hormones and general characteristics of the cell reaction to stress (proteins of heat shock) are also new findings. In the region of peptide hormones the author mentions findings pertaining to the mechanisms of development of adenohypophyseal adenomas, probably by the action of GHRH. It is assumed that some derivatives of prostaglandins will have an antiviral and anti-tumorous effect. An endogenous ligand for tetra-hydro-cannabinol receptors was isolated. Preventive administration of insulin protects relatives of patients with diabetes mellitus type I from the development of the disease. PMID- 8194085 TI - [Reactive oxygen products and antioxidants in cardiovascular diseases]. AB - Cardiovascular diseases account in this country for more than half the mortality. In the submitted review the authors discuss reactive oxygen products as one of the possible risk factors of the mentioned diseases. The second part of the paper deals with antioxidative enzymes and antioxidants in cardiovascular diseases as well as with possibilities of their use in prevention and improvement of adverse clinical conditions. PMID- 8194083 TI - Quantitative assay of S-100 protein in mouse brain cortex synaptosomes. AB - 1. Data on the presence of S-100 protein in synaptic endings are revised, and evidence is given in favor of its localization inside mouse brain cortex synaptosomes and on the surface of their external membrane. 2. For identification of the S-100-specific polypeptide, proteins of external synaptosomal membranes were iodinated with lactoperoxidase fixed on cyanogen bromide (CNBr)-Sepharose, and after synaptosome lysis S-100-positive material was isolated by means of affinity chromatography antibodies to S-100 protein (a-S-100)-Sepharose. The molecular weight of the polypeptide obtained corresponded to that of S-100 subunits (10 kD), and iodine incorporation pointed to its localization on the surface of synaptosomal membranes. 3. With the help of antibodies labeled with horseradish peroxidase (a-S-100-HP) or 125I (a-S-100-125I), which do not penetrate into noninjured synaptosomes, the amount of S-100 protein on synaptosomal membranes was found to be 18.5 ng/mg total protein (as assayed with a-S-100-HP) or 95.33 ng/mg (as assayed with a-S-100-125I). 4. At the same time, the total S-100 protein content in synaptosomes measured by means of radioimmune analysis after their complete lysis turned out to be 284 +/- 0.84 ng/mg, i.e., a part of S-100 seemed to be inside synaptosomes. 5. Cosedimentation of water soluble S-100 protein with the synaptosomal fraction during isolation was insignificant. Prefixation with glutaraldehyde or paraformaldehyde decreased the amount of material reacting with antibodies, possibly due to steric effects or denaturation of active centers. This could have influenced the earlier attempts to detect S-100 protein in synapses. Treatment of nonfixed synaptosomes with a conjugate of a-S-100 with colloidal gold made it possible to detect S-100 positive material on pre- and postsynaptic membranes, which confirms the biochemical data. PMID- 8194087 TI - [Growth hormone therapy in children with growth hormone deficiency: study of dose response relationship]. AB - BACKGROUND: Despite different age, stature, severity of hormone deficiency and target height children with growth hormone deficiency are usually given a uniform therapeutic dose of the preparation. Knowledge of the basic variables which influence individual therapeutic effects of growth hormone would make it possible to elaborate for individual patients a specific therapeutic strategy with the aim to cath up with the deficiency in height at an appropriate calendar age. METHODS AND RESULTS: The authors treated for a period of one year, using three different dosages of growth hormone, 25 prepubertal children with growth hormone deficiency (post-stimulation level < 8 mIU/l). Group A (9 children aged 11.2 +/- 2.0 years) were treated with 0.42 IU/kg/week, group B (7 children, aged 11.4 +/- 4.6 years) 0.7 IU/kg/week and group C (9 children, aged 10.2 +/- 2.4 years) 1.0 IU/kg/week. The preparation was administered daily before bedtime by the s.c. route. The growth rate during treatment increased from (mean +/- SD) 2.6 +/- 0.9 to 9.3 +/- 1.5 cm/year (group A), from 2.3 +/- 1.0 to 10.4 +/- 2.5 cm/year (group B) and from 3.1 +/- 0.7 to 12.6 +/- 1.9 cm/year (group C, p < 0.05 as compared with group A). The height age increased per year of treatment significantly more in children of group C (by 2.1 +/- 0.3 year) than in group A (by 1.6 +/- 0.3 year) or in group B (by 1.7 +/- 0.3 year). No difference was found between the groups in the ratio of changes in height and bone age. From 10 analyzed variables the growth rate during treatment is predicted above all by the therapeutic dose (r = 0.60), and to a lesser extent by the target height (r = 0.53). CONCLUSIONS: The therapeutic dose is the decisive parameter for prediction of the therapeutic effect of growth hormone in children with growth hormone deficiency. It is justified to modify the therapeutic dose individually with regard to the initial characteristic and therapeutic target of every given patient. PMID- 8194088 TI - [Relation between the blood coagulation status in hemodialyzed patients and arteriovenous fistula thrombosis--prospective study]. AB - BACKGROUND: In a number of haemodialyzed patients occlusion of arteriovenous fistulae for different reasons occurs. In these patients many haemocoagulation changes are described. The objective of the present work was to assess whether these occlusions are due to hypercoagulation. METHODS AND RESULTS: The investigation comprised 49 men and 32 women aged 49.3 +/- 9.3 years with renal insufficiency which had persisted for 28 +/- 17 months. Before the fistula was made, some parameters of haemocoagulation were examined. Depending whether within 6 months occlusion of the fistula occurred, the patients were divided into two groups. In a group of 18 patients with thrombosis of the fistula euglobulin fibrinolysis without stimulus (340 +/- 48 min.) was longer, also after veno occlusion (199 +/- 50 min.), as compared with the group without thrombosis (277 +/- 38 and 121 +/- 27 min. resp.) and the level of the inhibitor of the plasminogen activator (PAI-1) differed: 3.3 +/- 0.6 i.u. as compared with 2.6 +/- 0.8 i.u. P < 0.001 in all three parameters. In the other parameters no significant differences were found (haematocrit, fibrinogen, F VII, AT III, protein C, number and aggregation of thrombocytes) al in all instances P > 0.05. The sum of hypercoagulation findings was higher in the first group (5.3 +/- 1.5) than in the second group (3.5 +/- 1.5, P < 0.001). CONCLUSIONS: The authors assume that apart from other factors thrombosis of the fistula is influenced also by the haemocoagulation status, in particular fibrinolytic parameters. The latter may be supported also by other hypercoagulation factors which alone are ineffective. PMID- 8194089 TI - [The consequences of 17 November 1939 for Czech Medical Schools]. PMID- 8194090 TI - [Human values compatible with a strategy of a permanently sustainable life style]. PMID- 8194091 TI - [Incest offenders]. AB - BACKGROUND: Always raising attention has been devoted to sexual victimization of the juveniles and to its consequences lately. This report was aimed for learning frequency of the phenomenon in our country. METHODS AND RESULTS: Twenty-two men (mean age 22-45 years, mean year 37), are accused of sexual victimization of their step-daughters were examined. Contrary to other groups of sexual delinquents, their mean intellect was slightly above average, their sexual development was accelerated, sexual activity elevated. Three quarters of them were already previously prosecuted. Attention is drawn to the necessity to the evaluate "incestogenic families as a whole. In all instance it is necessary to make a considerate but detailed somatic and psychiatric examination of the victim with documentation which can be used also for criminal proceedings and psychiatric and sexuological assessment of the accused, incl. phallography. Accusations which indicate always grossly pathological relations are not necessarily always true. CONCLUSIONS: Incest and sexual victimization of children seem to be a little fashionable but even so a major affair we will probably face more frequently in next years. PMID- 8194092 TI - [Vulvar plethysmographic findings in transsexual women]. AB - BACKGROUND: Transsexualism is a complicated diagnostic category. From the differential diagnostic aspect it is necessary, among others, to rule out homosexuality. The objective of the present work was to express objectively vulvo plethysmographic reactions in transsexual women and to assess whether (or how) these reactions differ from findings in women with a homosexual orientation and to evaluate subsequently possibilities of vulvo-plethysmography in the differential diagnosis of homosexuality and transsexualism. METHODS AND RESULTS: Using an electro-capacitance vulvo-plethysmographic apparatus (designed by Figar et al.), 25 women (mean age 27.6 years, range 18-39 years) with an inverse sexual orientation--transsexuals--were examined. The results were compared with a group of 50 women, matched for age, who reported a homosexual orientation. On evaluation of the total number of recorded positive reactions to heterosexual and homosexual categories of exposed erotic stimuli the difference between the two groups on projection of 3 from 4 categories of these stimuli was highly significant (p < 0.001, chi 2 test). The differences were revealed in particular when evaluating preferences of pictures of sexual activities of partners. While in homosexually oriented women, as expected, preference of homosexual activities was recorded (74%) or a not clear-cut differentiation of these stimuli (26%), in 88% of transsexual women there was a more or less markedly expressed preference of heterosexual activities. CONCLUSIONS: Significant differences were found in results of vulvo-plethysmographic examinations of transsexual and homosexual women. This confirmed the expedience of using electro-capacitance vulvo plethysmography for the differential diagnosis of homosexual and transsexual women. PMID- 8194093 TI - [The first coitus as an outcome indicator]. AB - BACKGROUND: For evaluation of the health status in specialized medical disciplines and comparisons in different regions (countries, world-wide comparisons) the World Health Organization recommends and uses so-called indicators. In the sphere of human sexuality the use of such indicators is difficult, because it cannot be assessed by objective data. The purpose of the present study was to assemble information on the time and course of the first sexual intercourse of contemporary Czech girls. METHODS AND RESULTS: A total of 700 Czech girls aged 16-18 years were interviewed; all menstruated already. 344 girls (49.1%) reported that they had heterosexual intercourse: in 24.1% the first intercourse occurred at the age of 15 years and in 75.9% between 16 and 18 years. As to the place where it occurred, in 64% it was the parents' apartment. For the contemporary Czech society it is typical that in cca 20% the place of the first intercourse was a weekend house. In 8.5% of the girls the intercourse was implemented by force or under the influence of abundant alcoholic drinks. As far as prevention of unwanted pregnancy is concerned, in 42.0% no contraception was used, coitus interruptus was practiced in 25.3%--i.e. unreliable contraception in 67.3% of sexual intercourse. A condom was used by 30.4% partners, hormonal birth control only by 2.3% girls. CONCLUSIONS: Information on "outcome indicators" on the time of the first sexual intercourse and the place where it occurred was assembled. The authors recorded also data on the use of force, the influence of alcohol and the use of contraception. These data make it possible to gain an idea on the sexual life during adolescence. PMID- 8194094 TI - [The effect of chronic administration of ethanol on experimental adriamycin nephropathy]. AB - BACKGROUND: Alcoholic liver disease may be in humans frequently complicated by mesangial proliferation and sclerosis. The influence of chronic ethanol administration on experimental nephrotic syndrome has not been, however, studied yet. METHODS AND RESULTS: Experimental nephrotic syndrome was induced in rats by the i.v. administration of adriamycin in ethanol fed rats and in rats given common laboratory chow. Chronic administration of ethanol was in nephrotic rats accompanied by the exaggerated lipolysis (free fatty acids were in control nephrotic rats lower than in nephrotic ethylic rats 6 weeks after adriamycin administration: 914.8 + 96.8 mumol/l vs. 1186.3 + 178.7 mumol/l, p < 0.01) and increased proteocatabolism; the development of nephrotic syndrome was ameliorated, or at least delayed, however, in ethylic rats (control nephrotic rats had higher proteinuria than nephrotic ethylic rats 3 weeks after adriamycin administration: 5.79 + 3.15 vs. 0.55 + 0.34 g protein/mmol creatinine, p < 0.01). In autopsy, diffuse global glomerulosclerosis was found in control nephrotic rats with only mild focal and segmental changes in nephrotic ethylic rats. CONCLUSIONS: Chronic ethanol administration ameliorated and/or delays the development of nephrotic syndrome in adriamycin nephropathy in rats. Mechanism of this effect of chronic ethanol feeding remains to be elucidated. Metabolic, immunosuppressive and renal haemodynamic effects of ethanol should be taken into consideration. PMID- 8194095 TI - [Electric conductivity of erythrocyte sediments and red blood cell deformability]. AB - BACKGROUND: To assess the deformability of erythrocytes several methods can be used. The latter investigate either the properties of single blood cell or the properties of a red cell suspension. The objective of the present study was to assess whether experimentally induced deterioration of the red cell deformability can be recorded by measurements of the electric conduction of red cell sediment. METHODS AND RESULTS: In ten patients with disorders of the circulation 10 ml blood samples were taken, mixed with a solution of sodium citrate and centrifuged at 1250 g for 10 minutes. The separated blood cells were repeatedly centrifuged and rinsed. Red cell deformability was experimentally enhanced by incubation of erythrocytes in a Ringer-albumin solution. The change of deformability was detected by viscosimetry and assessment of the electric conduction of the red cell sediment, using a conductometer Radelkis 101 OK, the temperature of the sediment being 10 degrees C. The viscosity values of red cell suspensions with a haematocrit of 0.45 were assessed at six shear rates and they were in all instances higher after incubation of red cell suspensions, as compared with the viscosity of suspensions of fresh erythrocytes. The mean value of electric conduction of the sediment with a haematocrit of 0.45 before incubation was 0.132 mS and after 24 hours incubation 0.218 mS; the difference was statistically significant (p < 0.0005). CONCLUSIONS: Deterioration of red cell deformability is associated with improved electric conduction of the red cell suspension of sediment. It is possible to use assessment of electric conduction of the red cell sediment to assess erythrocyte deformability. The method is simple and cheap, as compared with the viscosimetric method. PMID- 8194096 TI - [Immunologic factors in human colostrum and milk]. AB - BACKGROUND: The mammary gland is at present conceived as an immunological secretory organ, capable of producing specific and non-specific factors transmitted into colostrum or milk. METHODS AND RESULTS: Colostrum was collected from the 1st to 3rd day after delivery, milk on the 4th to 19th day after delivery. Colostrum from 42 and milk from 63 mothers was examined. Levels of the following were assessed: IgG, IgM, IgD, IgA, sIgA, SCIgA, C3, C4, orosomucoid, prealbumin, alpha 1-antitrypsin, alpha 1-fetoprotein, alpha 2-macroglobulin, haemopexin, haptoglobin, beta 2-microglobulin, alpha 2-AP glycoprotein (methodradial immunodiffusion) and IgE (ELISA). Colostrum contains more IgG, SCIgA, almost three times more IgM, IgA and secretory IgA than milk. IgD was not detected. Factors of non-specific immunity were found only in low concentrations. CONCLUSIONS: Human colostrum and milk are from the immunological aspect an important liquid with proven bacteriostatic and inhibitory activity preventing penetration of pathogenic microorganisms and absorption of potential allergens into the digestive and respiratory tract of the neonate. From the immunological aspect it is essential to promote breastfeeding. PMID- 8194097 TI - [60 years' of the Trauma Hospital and 40 years' of the Institute of Traumatology Research in Brno]. PMID- 8194098 TI - [Why be a professor?]. PMID- 8194099 TI - A simultaneous evaluation method of purity and apparent stability constant of Ca chelating agents and selectivity coefficient of Ca-selective electrodes. AB - To determine the purity (q) of Ca-chelating agents (such as EGTA and BAPTA) and their apparent stability constants to Ca2+ (K') using Ca(2+)-selective electrodes precisely, we have developed a new method using the double-log optimization. Free Ca2+ concentration was plotted against the ratio of the concentrations of Ca(2+) bound to Ca(2+)-free chelator on double logarithmic co-ordinates in which a linear relationship with a slope of -1 must hold for the metal-chelator reaction with a stoichiometry of 1 to 1. Not only the q and K' values but also the selectivity coefficient of the electrode could be simultaneously estimated on the double-log plot through an optimizing method. Error analyses using a Monte Carlo simulation showed that the double-log plot is statistically more reliable and robust than the Scatchard plot and that the optimizing method is more objective and reliable than previous methods involving extrapolation and truncation procedures. PMID- 8194100 TI - Apparent stability constants and purity of Ca-chelating agents evaluated using Ca selective electrodes by the double-log optimization method. AB - Apparent calcium stability constants and the purity of Ca-chelating agents were evaluated using Ca(2+)-selective electrodes by the double-log optimization method [Oiki S. Yamamoto T. Okada Y. (1994) Cell Calcium, 15, 199-208]. The method was amended to allow evaluation of the free Ca2+ concentrations contaminating electrolyte solutions. The value thus estimated (3.7 microM) was not significantly different from the total contaminating Ca content measured by atomic absorption spectroscopy. The purity of EGTA of different commercial brands was found to be in the range from 95.5-98.0% and was almost stable over several years of storage. The impurity of EGTA was completely eliminated by baking at 150 degrees C for 3 h. The purity of BAPTA decreased from 85.8 to 77.2% after storing for 3 months at -20 degrees C. The impurity of BAPTA was also abolished by the same drying procedure. At physiological pH (7.30), the apparent stability constants (K's) of EGTA were determined to be 7.13 and 6.97 in KCl-based solutions of 0.10 M and 0.16 M ionic strength, respectively, at 25 degrees C in the absence of Mg. At pH 7.30 and 0.20 M ionic strength K' values of BAPTA were 6.50 at 22 degrees C and 6.69 at 37 degrees C. The K' value increased with decreasing ionic strength. PMID- 8194101 TI - Effects of Ca2+ deregulation on mitochondrial membrane potential and cell viability in nucleated cells following lytic complement attack. AB - We have previously shown [Papadimitriou JC. Ramm LE. Drachenberg CB. Trump BF. Shin ML. (1991) J. Immunol., 147, 212-217] that formation of lytic C5b-9 channels on Ehrlich ascites tumor cells induced rapid depletion of adenine nucleotides associated with prelytic leakage preceding cell death. Extracellular Ca2+ concentration ([Ca2+]e) reduction by chelation markedly delayed the onset of cell death, although the adenine nucleotide leakage was enhanced. In the present study, we examined the temporal relationships between ionized cytosolic Ca2+ ([Ca2+]i), mitochondrial membrane potential (delta psi m) and cell death in individual cells by digital imaging fluorescence microscopy (DIFM), during the earliest phase of C5b-9 attack. The results showed an immediate, > 20-fold rise in [Ca2+]i, rapidly followed by dissipation of delta psi m and subsequent acute cell death. These events were markedly delayed by chelation of Ca2+e, but not by nominally Ca2+ free medium. Differing from previous reports indicating propidium iodide labeling of viable cells bearing C5b-9 channels, with DIFM we observed nuclear fluorescence with that marker only in association with cell death. These findings indicate that Ca2+ influx through lytic C5b-9 channels is responsible for the massive increase in [Ca2+]i, as well as for the rapid loss of delta psi m, followed by acute cell death. When this [Ca2+]i increase is prevented, the cell death is probably related to metabolic depletion. PMID- 8194102 TI - Inositol 1,4,5-trisphosphate-, GTP-, arachidonic acid- and thapsigargin-mediated intracellular calcium movement in PANC-1 microsomes. AB - Inositol 1,4,5-trisphosphate (IP3)-, GTP-, arachidonic acid- and thapsigargin mediated Ca2+ release from endoplasmic reticulum (ER)-enriched microsomes was studied in a PANC-1 cell line. IP3 maximally caused an approximately 20% release of actively accumulated Ca2+. This effect was completely blocked by heparin. In the presence of 3% polyethylene glycol (PEG), GTP maximally discharged about 60% of Ca2+ from the microsomes. This effect involved a GTP hydrolytic process, not the IP3-activated Ca2+ channel. Arachidonic acid maximally released approximately 80% of Ca2+ from PANC-1 microsomes. Metabolites of arachidonic acid did not appear to be involved in arachidonic acid-mediated Ca2+ release. However, other fatty acids also induced similar releasing effects suggesting that arachidonic acid-induced Ca2+ release appeared to be non-specific. Thapsigargin was shown to inhibit Ca2+ accumulation into and induce Ca2+ release from PANC-1 microsomes. The thapsigargin-releasable Ca2+ pool included the IP3- or arachidonic acid sensitive pool. Studies on liposomes suggested that both arachidonic acid and thapsigargin did not exert either a Ca2+ ionophore-like or a membrane detergent like effect. The present results have provided evidence for the existence of multiple non-mitochondrial Ca2+ pools in PANC-1 cells. These Ca2+ pools could be released by various Ca2+ mediators via different mechanisms. PMID- 8194103 TI - PM-type calcium pumps are associated with higher plant cell intracellular membranes. AB - The supposition that all eukaryotic cell types contain a plasma membrane (PM) type Ca pump (i.e. a Ca pump which is directly-stimulated by calmodulin and located exclusively at the PM) has been questioned by recent data from higher plant cells. These studies suggest the presence of Ca pumps directly stimulated by calmodulin associated with an intracellular membrane (probably the endoplasmic reticulum, ER) in a variety of monocotelydonous and dicotelydonous species. Thus plants have a 'PM-type' Ca pump at an intracellular membrane. The evidence for this includes studies on isolated membranes, purification and functional reconstitution and phosphorylated intermediate formation. Plant cells also contain a homologue of the sarcoplasmic reticulum/endoplasmic reticulum (SR/ER) Ca pump, probably located at the ER. The implications of these new data for our appreciation of the structure, function and location of eukaryotic Ca pumps are discussed, together with recent data from the use of inhibitors specific to mammalian ER/SR Ca pumps. PMID- 8194104 TI - GHRP-6 induces a biphasic calcium response in rat pituitary somatotrophs. AB - The mechanism of action of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6), a synthetic peptide which specifically induces the secretion of growth hormone (GH) in rat somatotrophs, is still poorly understood. We have studied the effects of GHRP-6 on the cytosolic free calcium concentration ([Ca2+]i) of somatotrophs in primary culture. [Ca2+]i was monitored in individual somatotrophs by dual emission microspectrofluorimetry, using Indo-1 as the intracellular fluorescent Ca2+ probe. A short application of GHRP-6 (10(-5) M, 10 s) induced a biphasic Ca2+ response in most cells (44%), which consisted in a rapid and large rise in [Ca2+]i followed by sustained oscillations. This response is dose dependent in a range of concentrations from 10(-10) to 10(-5) M. The first phase of the GHRP-6 response persisted in the absence of Ca2+ in the extracellular medium, whereas the second phase was inhibited. The application of Ca2+ channel blockers like cadmium chloride (200 microM) or PN-200-110 (200 nM) also prevented the second phase. Conversely, when the cells were pretreated with thapsigargin (TG) (100 nM), the first phase of the GHRP-6 Ca2+ response was abolished, whereas the second phase alone was preserved. When the cells were depleted in PKC by incubation with 10(-6) M PMA for 24 h, the second phase of the GHRP-6 response was inhibited, and only the first phase was maintained. These results were corroborated by using phloretin, a PKC inhibitor. These data show that GHRP-6 induces a biphasic elevation of the [Ca2+]i in rat somatotrophs. The first phase is probably due to mobilization of the intracellular Ca2+ stores, whereas the second phase is a PKC-dependent process. PMID- 8194105 TI - omega-Conotoxin inhibits glucose- and arachidonic acid-induced rises in intracellular [Ca2+] in rat pancreatic islet beta-cells. AB - Earlier studies suggest that the accumulation of non-esterified arachidonic acid (AA) in islets following stimulation with glucose participates in the glucose induced secretion of insulin. A possible role for AA might include the facilitation of Ca2+ influx into islet beta-cells. Recently, we demonstrated that AA induces Ca2+ influx into purified rat pancreatic islet beta-cells, prepared by fluorescence-activated cell sorting (FACS). This effect was abolished in the presence of the Ca(2+)-chelator EGTA, but was only partially reduced by the dihydropyridine (DHP) L-type Ca(2+)-channel blocker, nifedipine. This raised the possibility that DHP-insensitive Ca2+ entry mechanisms may exist in pancreatic beta-cells, in addition to the known DHP-sensitive L-type Ca2+ channels. Here we report that omega-conotoxin (CTX), which blocks omega-type Ca(2+)-channels, inhibits AA-induced Ca2+ influx by a magnitude similar to that of nifedipine and that the combination of omega-CTX and nifedipine results in a nearly additive decrement in AA-induced increases in beta-cell cytosolic [Ca2+]. We further demonstrate that bovine serum albumin, which complexes free AA and prevents AA induced increases in cytosolic [Ca2+], also inhibits the glucose-induced increase in beta-cell [Ca2+]. These results suggest that rat pancreatic FACS-purified islet beta-cells express omega-type (DHP-insensitive) Ca(2+)-channels, in addition to DHP-sensitive Ca(2+)-channels. They further suggest that the glucose induced accumulation of non-esterified AA in the membranes of beta-cells serves to amplify glucose-mediated Ca2+ influx into the beta-cells. PMID- 8194106 TI - Three-dimensional dynamics of pseudopod formation and the regulation of turning during the motility cycle of Dictyostelium. AB - Employing a newly developed computer-assisted system for visualizing and quantitating cell motility in three dimensions, we have examined the 3 dimensional changes in cell shape and the dynamics of pseudopod extension during translocation of Dictyostelium amoebae. Amoebae exhibit a 3-dimensional behavior cycle with an average period of 1.5 min. The cycle includes a transient pseudopod extension phase in the x,y axis followed by a z-axis expansion phase. Anterior pseudopod extension in the x,y axis is accompanied by a decrease in height, not by uropod retraction. The increase in height is accompanied by uropod retraction. In the pseudopod extension phase in the x,y axes, pseudopods form either anteriorly or laterally, and either on or above the substratum. Pseudopods which initially form on the substratum in almost all cases continue to expand as the anterior end of the cell. In the case of lateral pseudopods, anteriorization leads to a turn. Approximately half of anterior pseudopod and two-thirds of lateral pseudopods which initially form above the substratum are retracted. These results suggest that pseudopod-substratum interaction plays a fundamental role in the regulation of directionality and turning in the translocation phase of the 3 dimensional behavior cycle. PMID- 8194108 TI - Occurrence of fibers and their association with talin in the cleavage furrows of PtK2 cells. AB - PtK2 cells of exceptionally large size were microinjected with fluorescently labeled probes for actin, myosin, filamin, and talin in order to follow the assembly of the contractile proteins into the cleavage furrows. Whereas in cells of normal size, there is usually a diffuse pattern of localization of proteins in the cleavage furrow, in these large, flat cells the labeled proteins localized in fibers in the cleavage furrow. Often, the fibers were striated in a pattern comparable to that measured in the stress fibers of the same cell type. The presence of talin in discrete plaques along fibers in the cleavage furrows of the large cells suggests a further similarity between cleavage furrow and stress fiber structure. The presence of filamin in the cleavage furrows also suggests the possibility of an overlapping mechanism in addition to that of a talin mediated mechanism for the attachment of actin filaments to the cell surfaces in the cleavage furrow. A model is presented that emphasizes the interrelationships between stress fibers, myofibrils, and cleavage furrows. PMID- 8194107 TI - Effects of thymosin beta 4 and thymosin beta 10 on actin structures in living cells. AB - The beta-thymosins are a family of small proteins originally isolated from the thymus. Recently, two of the major mammalian isoforms, thymosin beta 4 (T beta 4) and thymosin beta 10 (T beta 10), are identified as significant actin monomer sequestering proteins which may be involved in regulating actin filament assembly. To study the cellular function of beta-thymosins, we have used isoform specific antibodies to determine their concentration and intracellular distribution, and examined the effects of inducing overexpression of T beta 4 and T beta 10 on actin filament structures. Immunofluorescence labeling of peritoneal macrophages showed that both beta-thymosins are uniformly distributed within the cytoplasm. cDNA-mediated overexpression of beta-thymosins in CV1 fibroblasts induced extensive loss of phalloidin-stained actin stress fibers. Stress fibers in the cell center were more susceptible than those at the periphery. There was a decrease in the number of focal adhesions, as evidenced by a decrease in discrete vinculin staining and an increase in diffuse vinculin fluorescence. The majority of the transfected cells had normal shape in spite of extensive loss of actin filaments. Occasionally, cells overexpressing beta-thymosin were observed to divide. In these cells, beta-thymosin was excluded from the midbody which contains an actin filament-rich contractile ring. Our results indicate that T beta 4 and T beta 10 are functionally very similar and both are effective regulators of a large subset of actin filaments in living cells. PMID- 8194109 TI - Novel 130-kDa rat liver myosin-1 will translocate actin filaments. AB - We have recently purified and characterized from rat liver, polypeptides of 110 kDa and 130-kDa which possess several characteristics of myosin-1 [Coluccio and Conaty: Cell Motil. Cytoskeleton 24:189-199, 1993]. What roles these myosin-1 molecules play in hepatocytes is not yet defined. One hypothesis is that they are involved in either intracellular transport or locomotion. As a first step in establishing their function, we have investigated whether these molecules are capable of supporting motility in vitro. Our results clearly demonstrate that the isolated 130-kDa-calmodulin complex will translocate filaments at a rate of 0.03 0.05 microns/sec; motility is inhibited in free calcium ion concentrations above 0.1 microM. This inhibition is reversed with the addition of exogenous calmodulin. These results provide supporting evidence of a motile role for the 130-kDa-calmodulin complex in vivo. This is the first demonstration that in higher eukaryotes, myosin-1 from a tissue other than intestine will support motility. Partial peptide sequence analysis indicates that the 130-kDa polypeptide resembles the recently described myr 1 [Ruppert et al.: J. Cell Biol. 120:1393-1403, 1993] or MM1 alpha [Sherr et al.: J. Cell Biol. 1405-1416, 1993] gene product. PMID- 8194110 TI - Dithiothreitol prevents membrane fusion but not centrosome or microtubule organization during the first cell cycles in sea urchins. AB - Dithiothreitol (DTT), a disulfide reducing agent, inhibits the fusion of male and female pronuclei within the activated cytoplasm of sea urchin eggs. The migrations of the pronuclei are not affected by DTT, indicating that microtubule function is not impaired. Centrosomal antigens are detected in the sperm aster and in all subsequent microtubule-based configurations. Nuclear membranes never fuse and the chromatin of male and female pronuclei never mix in the DTT-treated cells. During prophase, when nuclear envelopes break down to undergo mitosis, both sets of chromosomes undergo condensation cycles independent from each other. Both pronuclei initially stain for centrosomal material and surrounding microtubules. With time, the female's centrosomal material as well as the microtubules disappear while the male forms a bipolar spindle. Interestingly, one pole of the paternal mitotic apparatus communicates with the separate maternal chromatin, forming a half spindle which moves the egg-derived chromatin towards its pole. At the time for cell division, the individual karyomeres are not able to fuse their nuclear membranes to reconstitute the blastomere nuclei. When DTT is applied at prometaphase of the first cell cycle, the chromosome cycle continues until next metaphase. Centrosomes also continue their cycle and undergo somewhat atypical splitting during the time for second telophase. Division furrows are initiated but aborted. These results support the hypothesis that disulfide groups are required for membrane fusion of the pronuclei, for membrane fusion of the karyomeres, and for the completion of the division furrow to achieve successful cell division. PMID- 8194111 TI - Role of MAPs and motors in the bundling and shimmering of native microtubules from insect ovarioles. AB - Bundles of native microtubules isolated from the ovarioles of hemipteran insects are seen to shimmer when observed using dark-field microscopy. This novel form of microtubule motility becomes even more obvious when the isolated bundles are detergent-extracted and reactivated. We have studied the nucleotide-specificity and the drug-sensitivity of microtubule shimmering in order to obtain information regarding the nature of the motor protein responsible, and to compare its properties with those of previously characterised microtubule motors. The involvement of structural MAPs in the shimmering and in maintenance of microtubule bundles in this system has also been investigated. PMID- 8194112 TI - Microtubules with altered assembly kinetics have a decreased rate of kinesin based transport. AB - Microtubules treated with the gamma-diketone 2,5-hexanedione (2,5-HD) have altered assembly behavior characterized by precocious nucleation and rapid elongation. By measuring the rate of microtubule transport, we have examined the potential functional significance of this 2,5-HD-induced microtubule modification. 2,5-HD-treated microtubules were transported at only 70% of the rate of control microtubules in a simple kinesin-based motility assay on glass coverslips using video and computer enhanced differential interference contrast microscopy. Since 2,5-HD is capable of forming both pyrrole adducts and crosslinks with tubulin, the contributions of pyrrole formation and crosslinking to slowed microtubule transport were determined. 3-Acetyl-2,5-hexanedione (AcHD), a pyrrole forming, non-crosslinking congener of 2,5-HD which does not alter microtubule assembly, did not produce slowed microtubule transport as occurs with 2,5-HD. However, glutaraldehyde, a pyrrole-independent crosslinking agent which alters microtubule assembly in the same way as 2,5-HD, slowed microtubule transport. These results indicate that a 2,5-HD-induced microtubule modification, possibly a crosslink-related conformational change, produces both an alteration in the kinetics of assembly and an alteration in the microtubule-motor interaction. PMID- 8194113 TI - Role of microtubules in random cell migration: stabilization of cell polarity. AB - The role of microtubules in random cell migration was investigated using time lapse videomicroscopy to record in vitro the shape and motile behavior of guinea pig alveolar macrophages before and after disrupting microtubules with colcemid. Cell migration was quantified in terms of directional persistence time and speed. Motility was also correlated with morphological polarity: cells having a single lamellipodal region (monopolar cells) migrated, whereas those lacking a lamellipod (apolar cells) or with opposing lamellipodal regions (bipolar cells) did not migrate. Within 2 hours, colcemid caused a shift in polarity from 80% monopolar cells to 40% monopolar and 40% bipolar cells and a corresponding decrease from 80% to 40% in the fraction of migrating cells. Mean persistence time and speed decreased only slightly (approximately 20%) for those cells (still monopolar) which continued to migrate in the presence of colcemid. Persistence time and speed actually increased for many individual cells, indicating that random migration did not require intact microtubules. We conclude that colcemid treatment destabilizes monopolarity, leading to the gradual loss of monopolarity and consequent inhibition of migration. While a cell remains monopolar, it will continue to migrate even in the absence of intact microtubules, but microtubules are required for the long-term maintenance of cellular monopolarity and, thus, for continued motility. PMID- 8194114 TI - [Diabetic maculopathy]. AB - After review of literature about diagnosis and treatment of diabetic macular edema own results with mean observation time of 5 months are presented. After photocoagulation the visual acuity improved in eyes with focal maculopathy in 28.9%, stabilized in 62.2% and in 8.9% it was worse. In eyes with diffuse maculopathy improvement was observed in 29.6%, stabilisation only in 37%, deterioration in 33.3%. In ischemic maculopathy the visual acuity improved in 23%, stabilised in 76.9% and in none case deterioration was stated. We plan to reevaluate our results during longer observation time. PMID- 8194115 TI - [From Beer's knife to the tunnel incision]. AB - The authors present an account on the development of surgical techniques used in operations of cataract. Surgery of cataract was started on April 8, 1745 when the Frenchman Jaques Daviel made the first extraction of an opaque lens by limbal incision. This new method was enforced, however, very slowly and only after 100 years it finally celebrated victory over the hitherto widely used reclination. In the fifties of the present century a great advance in the surgery of cataract was the introduction of cryoextraction; at the First Ophthalmological Clinic a double jacket instrument was designed which was filled with crushed CO2. The first cryoextraction was made at the authors' department on October 7, 1964, it was the very first operation of this type in Czechoslovakia. PMID- 8194116 TI - [Artephakic retinal detachment]. AB - The authors investigated the incidence of retinal detachment from a total of 3,802 artephakic eyes in which between September 1988 and June 1993, an intraocular lens was implanted at the First Eye Clinic in Prague. Detachment of the retina occurred in 10 eyes, 9 patients (0.3%). Risk factors for detachment of the retina were loss of the vitreous body during extraction of the cataract, a previous injury, myopia and YAG capsulotomy. Cryosurgery was selected in 76.9%, pars plana vitrectomy with an internal tamponade using silicon oil in 15.4% of the eyes. The retina attached in 92.3%, the visual acuity improved, as compared with the condition before operation of the detached retina, in 58.4% of successfully operated patients. Extracapsular extraction of the lens with implantation of an intraocular lens significantly reduced the incidence of retinal detachment. The prognosis of artephakic retinal detachment is comparable with the prognosis of aphakic retinal detachment. PMID- 8194117 TI - [History of the first Czech Ophthalmology Clinic]. PMID- 8194119 TI - [Anterior ischemic optic neuropathy]. AB - Anterior ischemic optic neuropathy is based on the lesion of blood supply to the optic nerve head. The disease presents decrease of visual acuity and altitudinal field defects with optic dics oedema in ophthalmoscopic view, which progresses in optic atrophy. Anatomy, pathogenesis, causes, clinical picture and management are discussed. 20% of patients from the group treated with vasodilatants and 50% of those treated with corticosteroids improved their visual acuity. PMID- 8194118 TI - [Endogenous uveitis]. AB - In a brief historical review of views on inflammatory affections of the uveal tissue the authors focused attention also on distinguished personalities in Czech ophthalmology who worked at the Czech Ophthalmological Clinic and participated in the development of uveology. Based on their own observations, they give an account on of their experience with the diagnosis of endogenous uveitis. Consistent with the world literature, they were able to reveal in a group of 174 patients with endogenous uveitis that the condition was associated with a systemic disease in 30%, in 9% they found an infectious aetiology and the remaining 61% were described as idiopathic endogenous uveitis. From the group of idiopathic uveitis they separated clinical entities diagnosed in 29%. PMID- 8194120 TI - [Glaucoma]. PMID- 8194121 TI - Effects of clofibrate, phthalates and probucol on ubiquinone levels. AB - Rats were exposed through their diet to clofibrate, di(2-ethylhexyl)phthalate or probucol for 6 weeks and the levels of ubiquinone (UQ), cholesterol and dolichol were monitored in liver, muscle, heart, brain and blood. The levels of UQ-9 and 10 were increased by clofibrate and, in particular by phthalate administration. With the latter agent this increase in liver was fourfold, in muscle was twofold and levels in the heart and blood increased by 20%, whereas there was no change in the brain. Probucol led to a moderate decrease in the level of UQ in liver, muscle and blood, but not in heart or brain. The extent of reduction of UQ was not modified by any of the treatments employed. Probucol did not have any effect on tissue or blood cholesterol levels, whereas clofibrate or phthalate elicited a variable response, including both increases and decreases depending on the tissue analyzed. Phthalate treatment increased the dolichol content to some extent in all tissues and in blood, but the level of this lipid was not modified upon clofibrate or probucol treatment. These results demonstrate that tissue and blood levels of UQ can be increased by exposure to appropriate chemical agents without elevating the concentration of cholesterol. PMID- 8194122 TI - Effects of microsomes and liposomes on glutathione transferase catalysed conjugation of benzo[a]pyrene diol epoxide with glutathione. AB - trans-7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] is rapidly inactivated in aqueous solvents due to hydrolysis to tetraols. No significant effect on the rate of hydrolysis is observed in the presence of glutathione (GSH)-depleted cytosol. However, when the cytosolic fraction is replaced by a mixture of glutathione (GST)-isoenzymes (corresponding to about 10% of the cytosolic protein) a significant inhibition of the rate of hydrolysis is observed, indicating a physical interaction between the diol epoxide and GST. This is compatible with the proposed role of certain GST-isoenzymes as intracellular carriers for lipophilic compounds. Studies on the accessibility of (+)-anti-BPDE to hydrolysis and GST-catalysed conjugation with GSH reveal that the presence of rat liver microsomes or liposomes, in particular those composed of the neutral phospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), very effectively protect the diol epoxide from hydrolysis. Addition of cytosolic fraction depleted of GST to a mixture of GST isoenzymes and microsomes or liposomes do not significantly increase the rate of GSH-conjugation. This implies the absence of high molecular factors in the cytosol that may increase the accessibility of (+)-anti-BPDE and thus promote conjugation. In contrast to liposomes of PC and PE, those composed of the negatively charged phospholipids phosphatidylserine (PS) and phosphatidylinositol (PI) are considerably less efficient in protecting (+)-anti-BPDE. In fact, these lipids seem to promote hydrolysis, an effect which is lost when PS and/or PI are present together with PC and PE. Taken together, the results presented here suggest that (+)-anti-BPDE and most probably other diol epoxides, are not accessible for GSH-conjugation by direct interaction between GST and the membrane bound compound. Moreover, there is little support for the existence of cytosolic components that increase the accessibility of (+)-anti-BPDE for conjugation. In agreement with previous results using other compounds, the results indicate that only the fraction of diol epoxide that is free in solution is accessible for conjugation with GSH. PMID- 8194123 TI - The scavenging of hydroxyl radical(.OH) by a prostacyclin analogue, taprostene. AB - A possible mechanism by which prostacyclin (PGI2) analogues provide beneficial effects including improved survival in shock experimentally induced by endotoxin, polytrauma or hypovolemia was studied. Since several studies have implicated oxygen free radical-mediated tissue damage, we investigated whether PGI2 analogues exert their 'cytoprotective' effects by inhibiting overproduction of oxygen free radicals. For this reason, the efficiency of Taprostene to scavenge hydroxyl radicals (.OH) and to possibly prevent the subsequent formation of reactive oxygen species was studied. Competition experiments were performed in which the .OH generated by H2O2/Fe2+ abstracted a hydrogen from Taprostene (CG 4203) [5Z,13E, 9,11,15S)-2,3,4-trinor-1,5-inter-m-phenylene-6,9-epoxy-11,15-di hyd roxy-15-cyclohexyl-16,17,18,19,20-pentanor-prosta-5,13-dieno ic acid sodium salt], and the resulting carbon-centered radical was trapped with the spin trap 3,3,5,5-tetramethyl-1-pyrroline-N-oxide (M4PO). This spin trap reacted with .OH to yield an M4PO-OH spin adduct observable by Electron Paramagnetic Resonance (EPR) spectroscopy and resulted in the rate constant, k2 = 1.5 x 10(10) M-1s-1, for the reaction between .OH and Taprostene. The results show that Taprostene is an efficient .OH scavenger. In addition, reactions of hypochlorous ion (-OCL) with hydrogen peroxide (H2O2) in the presence of Taprostene were monitored using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and M4PO dissolved in deuterium oxide. PMID- 8194124 TI - Detection of sulfur mustard-induced DNA modifications. AB - Sulfur mustard is acutely toxic to the skin, eyes, and respiratory tract, and is considered carcinogenic to humans by the IARC. Since all of these toxicities are thought to be initiated by DNA alkylation, the level of DNA damage should serve as a biomarker for exposure. To develop methods of detecting this damage, DNA was modified by [14C]-labeled sulfur mustard and DNA adducts were released by mild acid hydrolysis. Radioactivity co-eluted on HPLC analysis with marker 7-(2 hydroxyethylthioethyl) guanine and 3-(2-hydroxyethylthio-ethyl) adenine synthesized from 2-chloroethyl 2-hydroxy-ethyl sulfide. Unambiguous identification of the major adduct, 7-(2-hydroxy-ethylthioethyl) guanine, was provided by gas chromatography combined with mass spectrometric detection. The most abundant adduct, 7-(2-hydroxyethyl-thioethyl) guanine, accounted for 61% of the total alkylation and could be detected as a fluorescent HPLC peak with a detection limit of 10 pmol. To demonstrate the applicability of this method to biological samples, DNA was extracted from the white blood cells of human blood exposed to 131 microM sulfur mustard in vitro and shown to contain 470 pmol of 7 (2-hydroxyethylthio-ethyl) guanine per mg of DNA. PMID- 8194125 TI - Hepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P450 2E1. AB - The involvement of the alcohol-inducible cytochrome P450 2E1 in the hepatoprotective mechanism of the plant flavonoid extract silymarin, and its main active component silybin, was investigated in isolated hepatocytes. Allyl alcohol toxicity, associated lipid peroxidation and GSH depletion was efficiently counteracted by silymarin (0.01-0.5 mM), and at higher concentrations by silybin. Cell damage by t-butyl hydroperoxide was also prevented by silymarin and silybin, but less efficiently. However, the covalent binding of the acetaminophen intermediate, formed via P450 2E1, was unaffected by addition of the flavonoids. Silybin did not influence microsomal 2E1-catalyzed demethylation of N nitrosodimethylamine. Neither did demethylation of N-nitrosodimethylamine or aminopyrine by isolated microsomes affect the in vivo administration of silybin. Addition of silymarin or silybin to primary cultures of isolated hepatocytes did not prevent cell damage induced by exposure to the P450 2E1 substrate CCl4. In contrast, the mere presence of low concentrations (25-50 microM) of these compounds was found to inhibit cell attachment to the matrix and eventually resulted in cell damage. We conclude that contrary to earlier reports we found no evidence for an interaction of silymarin or silybin with cytochrome P450 2E1. This suggests that the antioxidant and free radical scavenging properties may account for most of the therapeutic effect of these compounds. The untoward effect of silymarin on cultured cells may have consequences when considering long term prescription of this therapeutic agent. PMID- 8194126 TI - Analysis of the binding of chlorpheniramine to human serum albumin by spectroscopic techniques. AB - The binding of chlorpheniramine (CFA) to human serum albumin (HSA) has been studied by absorption and fluorescence techniques. By deconvolution of the UV spectra into five Gaussian bands it can be observed that the band at 214 nm is the most sensitive for following the interaction CFA-HSA. Such interaction causes a redshift in the band at 227 nm to 235 nm, and an isosbestic point surges at 236 nm. Moreover, the fluorescence quenching depends on the excitation wavelength. By excitation at 278 nm, 25% of the native fluorescence is quenched, but only 6% is quenched by excitation at 290 nm. From these spectroscopic studies our results are compatible with the possibility that the interaction could take place mainly on the subdomain IIIA. PMID- 8194127 TI - Ultraviolet irradiation and cytokines as regulators of HIV latency and expression. AB - The ability of the human immunodeficiency virus (HIV) to persist and replicate in human CD4+ T lymphocytes and mononuclear phagocytes is under the control of both virally encoded proteins and a variety of host-related factors. Ultraviolet (UV) light has been shown to induce transcription and expression of HIV. Both DNA damage and repair and DNA damage/repair-independent pathways caused by UV irradiation lead to expression of proviral HIV genomes via activation of the cellular transcription factor NF-kappa B. Transgenic mice that contain either long terminal repeat (LTR)-reporter genes or HIV genomes, either full length or deleted in the gag-pol region, express RNA and proteins at the epidermal level, particularly after UV irradiation. Furthermore, UV-triggered release of soluble factors capable of inducing expression of HIV in non-irradiated cells has been observed. Among other host factors, the functional network of pro-inflammatory and immunoregulatory cytokines has been demonstrated to act as a potent regulator of HIV replication, at least in different in vitro systems of infection. PMID- 8194128 TI - Effect of human immunodeficiency virus type 1 (HIV-1) monocyte-derived macrophages infection on the manganous superoxide dismutase gene expression. AB - Clinical and biological features indicate that a dysregulation of microbicidal activity occurs in the cells of mononuclear phagocytic lineage of HIV-1-infected patients. Thus, the regulation of MnSOD gene expression has been investigated during the 10 h following in vitro HIV macrophage infection. As previously reported, in HIV-1 LAI-infected macrophages a high expression of the MnSOD gene is observed 2 and 4 h after infection. These results are confirmed when cells are infected with three macrophage-tropic strains HIV-1, DAS, PAR and Bal. Moreover, the detection of the MnSOD gene expression in the macrophage cultures is associated with the cellular tropism of the viral strains used. The binding of recombinant GP160 by itself is not sufficient to induce MnSOD expression. In fact, the same MnSOD gene induction was obtained with the heat inactivated viral isolates, indicating that these phenomena are due to the viral entry. On the other hand, phagocytosis of latex beads triggers a high expression of the MnSOD gene in macrophages, showing that phagocytosis of HIV may be sufficient to induce the expression of that gene. Taken together, these results indicate that the MnSOD gene expression observed within 10 h following infection of macrophages is mainly related to membrane biophysical unspecific modifications. PMID- 8194129 TI - Biological origin of free radicals, and mechanisms of antioxidant protection. AB - Reduced intermediates of molecular oxygen, such as superoxide and hydrogen peroxide, are ubiquitous inorganic products of normal aerobic metabolism. Certain cells, such as phagocytes, have evolved to use superoxide and hydrogen peroxide for purposeful chemistry beneficial to the host, but most cells require antioxidant protection against excessive production of these intermediates. Superoxide and hydrogen peroxide are themselves poorly reactive in aqueous solution, and unable to directly damage DNA, lipids and proteins. Excessive generation, however, of superoxide and hydrogen peroxide invariably accompanies molecular damage. Substantial evidence suggests that conversion of these poorly reactive intermediates of oxygen to highly reactive forms requires the participation of transition metal ions, particularly iron. Iron ions react with hydrogen peroxide (Fenton chemistry) to generate hydroxyl radicals that can damage all organic molecules. PMID- 8194130 TI - Oxygen radical release by neutrophils of HIV-infected patients. AB - Neutrophils from asymptomatic HIV-infected patients have an increased Nitroblue tetrazolium (NBT) reduction, that is an increased production of oxygen radicals. Plasma from these patients can activate normal neutrophils to an increased NBT reduction and the neutrophil activating factor thus seems to be mainly plasma bound. Further, the patients also have increased levels of plasma malondialdehyde and thus an increased lipid peroxidation. Plasma cysteine levels are low, a sign of increased consumption of antioxidants. Treatment of the asymptomatic HIV infected patients with N-acetylcysteine corrected the plasma cysteine levels and had some beneficial effects, but did not inhibit the increased radical production by the neutrophils. PMID- 8194131 TI - Imbalance between oxidants and antioxidants in the lungs of HIV-seropositive individuals. AB - Following the initial infection with HIV, there is evidence of immune dysfunction despite an apparent normal clinical state. In the context that the lung is a major site affected by opportunistic infection, and that some components of the immune system are activated during early HIV infection, we hypothesized that there may be activation of alveolar macrophages (AM), a key component of the pulmonary host defense system. Compared to cells from normal individuals, AM of asymptomatic HIV-seropositive (HIV+) individuals (CDC-stage II) spontaneously released significantly more superoxide anion (O2-.) (P < 0.002). The O2-. release by AM of HIV-infected individuals was comparable to the spontaneous O2-.-release by AM of cigarette smokers (P > 0.6), a condition often associated with chronic damage of respiratory tissues. The destructive effects of oxidants are normally suppressed by antioxidant defense systems. Evaluation of the concentrations of glutathione, a major component of the pulmonary antioxidant protective screen, demonstrated that the HIV+ state is also characterized by a significant glutathione deficiency in lung epithelial lining fluid (P < 0.001) and in venous plasma (P < 0.001). This suggests that the alveolar structures of HIV+ individuals are continuously exposed to increased amounts of toxic oxygen radicals without adequate protection, i.e. the reactive oxygen metabolites may cause sufficient tissue damage culminating in interstitial lung disease. Further, since many immune functions are susceptible to injury by extracellular oxidants, the consequences of an unsuppressed oxidant burden in the lung may amplify the extent of local immunocompromise. In addition, since glutathione plays an important role in modulating lymphocyte activation and effector functions independent of its antioxidant activity, the systemic glutathione deficiency may contribute to the progressive global immune dysfunction that characterizes HIV infection. PMID- 8194132 TI - Increased production of reactive oxygen species in pharmacologically immunosuppressed patients. AB - HIV-infected patients and transplanted patients share similar immunosuppressed status. Recent insights gained through the field of heart transplantation may help to clarify the role of reactive oxygen species in HIV-infected patients. PMID- 8194133 TI - Antioxidant status and lipid peroxidation in patients infected with HIV. AB - Deficiency in antioxidant micronutrients have been observed in patients with AIDS. These observations concerning only some isolated nutrients demonstrate a defect in zinc, selenium, and glutathione. An increase in free radical production and lipid peroxidation has been also found in these patients, and takes a great importance with recent papers presenting an immunodeficiency and more important an increase in HIV-1 replication secondary to free radicals overproduction. We have assessed different studies, trying to obtain a global view of the antioxidant status of these patients. In adults we observe a progressive decrease for zinc, selenium, and vitamin E with the severity of disease, except that selenium remains normal at stage II. However, the main dramatic decrease concerns carotenoids whose level at stage II is only half the normal value. To understand if these decreases in antioxidant and increases in oxidative stress occur secondary to the aggravation of the disease or, conversely, are responsible for it, we undertook a longitudinal survey of asymptotic patients. The preliminary results of this evaluation are presented. Paradoxically, lipid peroxidation is higher at stage II than at stage IV. This may be consecutive to a more intense overproduction of oxygen free radicals by more viable polymorphonuclear (PMN) at the asymptomatic stage. The free radicals production and lipid peroxidation seem secondary to a direct induction by the virus of PMN stimulation and cytokines secretion. N-Acetyl cysteine or ascorbate have been demonstrated in cell culture to be capable of blocking the expression of HIV-1 after oxidative stress and N acetyl cysteine inhibits in vitro TNF-induced apoptosis of infected cells. In regard to all these experimental data, few serious and large trials of antioxidants have been conducted in HIV-infected patients, although some preliminary studies using zinc or selenium have been performed. In our opinion it is now time to evaluate in humans the beneficial effect of antioxidants. The more promising candidates for presenting synergistic effects when associated with N acetyl cysteine seem to be beta-carotene, selenium and zinc. PMID- 8194134 TI - Selenium deficiency in HIV infection and the acquired immunodeficiency syndrome (AIDS). AB - Selenium is required for activity of the enzyme glutathione peroxidase, and selenium deficiency may be associated with myopathy, cardiomyopathy and immune dysfunction including oral candidiasis, impaired phagocytic function and decreased CD4 T-cells. We assessed selenium status in 12 patients with AIDS compared to normals and found significantly low plasma and red blood cell levels. Plasma selenium in AIDS was 0.043 +/- 0.01 microgram/ml vs 0.095 +/- 0.016 in controls (P < 0.001). Selenium status correlated with serum albumin (r = 0.77; P < 0.001) and 60% had documented GI malabsorption as determined by abnormal D Xylose tests. In a subsequent study blood selenium and glutathione peroxidase were diminished in 12 AIDS and 8 ARC patients compared with normals (all P < 0.001). For glutathione peroxidase the mean levels were decreased by 45% in AIDS and 27% in ARC versus controls (P < 0.001). Both plasma selenium and glutathione peroxidase significantly correlated with total lymphocyte counts (r = 0.65; P < 0.001; glutathione peroxidase and lymphocyte counts). This occurred in both homosexuals and drug users with AIDS and irrespective of the presence or absence of diarrhea or GI malabsorption. To determine if tissue levels of selenium were also depleted we studied cardiac selenium levels in autopsy AIDS hearts compared to age and sex matched controls. Cardiac selenium in AIDS was 0.327 +/- 0.082 micrograms/g dry weight versus 0.534 +/- 0.184 in controls (P < 0.01). Two cases had histologic cardiomyopathy pathologically consistent with the cardiomyopathy described in Keshan disease associated with low selenium blood levels. To further assess mechanisms of nutrient and selenium deficiency in AIDS we studied dietary intake in outpatients and inpatients with various stages of HIV infection. Inadequate selenium intake based on a computer (Nutritionist 3) analysis of 72 h diet records was present in only 17% of clinically stable HIV positive outpatients and 71% of inpatients with AIDS. CONCLUSIONS: Selenium deficiency is common in HIV positive patients as documented by low plasma and red blood cell levels of selenium, diminished activity of glutathione peroxidase, and low cardiac selenium levels in AIDS hearts. Patients with AIDS tend to have more severe deficits than those with earlier stages of HIV infection. The selenium deficit in blood does correlate with serum albumin levels and total lymphocyte counts. Poor dietary intake and malabsorption could lead to this condition which has important implications for both cardiac and immune functions in HIV positive patients. PMID- 8194135 TI - Could oxidative stress initiate programmed cell death in HIV infection? A role for plant derived metabolites having synergistic antioxidant activity. AB - Evidence supports the premise that a pro-oxidant condition exists in HIV seropositive patients, a result of an overabundance in production of reactive oxygen forms combined with a multilevel deficiency in nutritional and metabolic sources of antioxidants. Apoptosis (a programmed cell death) is recognized as a possible pathway of immune cell loss in patients with HIV infection and AIDS. The cascade of events that results from 'oxidative stress' (OS) is markedly similar to that which can initiate apoptosis and includes oxidation of cellular membranes, alteration of metabolic pathways, disruption of electron transport systems, depletion of cellular ATP production, loss of Ca2+ homeostasis, endonuclease activation and DNA/chromatin fragmentation. Downstream events secondary to these effects may also play a role in activation of latent virus and subsequent viral replication. Primary and secondary metabolites found in plants act as synergistic antioxidants, and can protect plants from oxidation-induced cell death. Experiments have shown that some of these same metabolites can inhibit cell killing by HIV. Can these compounds be useful in inhibiting viral activation and the death of immune cells in HIV/AIDS through their synergistic antioxidant properties? A brief review of the evidence for OS in HIV is presented and the potential basis for OS playing a role in the initiation of cell death and viral replication is explored. The functional antioxidant activities of plant metabolites are illustrated and the use of these synergistic antioxidants from plants are proposed as a mechanism by which viral replication and cell killing in HIV infection can be inhibited. PMID- 8194136 TI - Effects of glutathione precursors on human immunodeficiency virus replication. AB - Asymptomatic human immunodeficiency virus (HIV)-seropositive individuals have reduced glutathione (GSH) levels. This has led to the suggestion that elevated intracellular thiols levels may inhibit HIV replication and progression of the disease. We confirmed that N-acetyl-L-cysteine (NAC), a cysteine prodrug which maintains intracellular GSH levels during oxidative stress, inhibits in the chronically infected U1 cells, the stimulation of HIV replication induced by phorbol 12-myristate 13-acetate (PMA), interleukin-6 (IL-6) or granulocyte macrophage colony stimulating factor (GM-CSF). However, we found no significant inhibition of PMA-mediated long terminal repeat (LTR)-directed beta-galactosidase expression in transiently transfected Jurkat T-cells. We have compared NAC effects with the effects of other GSH precursors on HIV expression. Treatment of the U1 cell line by L-2-oxo-4-thiazolidine carboxylic acid (OTC), which is converted to cysteine by 5-oxoprolinase, or by homocysteine (HC), a natural cysteine precursor, reduced the PMA-induced HIV expression, but surprisingly, markedly stimulated the expression mediated by IL-6 and GM-CSF. Several experiments to investigate the effect of OTC on LTR transactivation were carried out, but beta-galactosidase activity was never modified in a significant fashion in PMA-induced Jurkat T-cells after OTC treatment. Furthermore, HC stimulated the PMA-mediated HIV-LTR transactivation in Jurkat T-cells. GSH assays showed that treatment of U937 and Jurkat T-cells with NAC and OTC moderately increased the GSH level, while HC led to a significantly higher increase of the thiol level. In conclusion, it appeared that an increase of the GSH intracellular level did not lead solely to an inhibition of HIV replication but could also lead to an activation of viral expression. This seemed the case when HIV replication was stimulated by compounds which act mainly at a post-transcriptional level. PMID- 8194137 TI - HIV-1 reactivation after an oxidative stress mediated by different reactive oxygen species. AB - An important aspect of infection by the human immunodeficiency virus (HIV-1) type 1 is its long clinical latency period, suggesting that the provirus may remain latent for extended periods of time after primary infection. Numerous factors such as cytokines, tumor promoters, co-infection by several viruses and physical agents are able to reactivate latent virus. Since a common denominator, shared by several of these agents, is their ability to cause stress conditions, we have examined the effects of an oxidative stress mediated by reactive oxygen species on HIV-1 latently infected monocytes (U1) or lymphocytes (ACH-2). Exposure of these two cell lines to hydrogen peroxide causes a decrease of cell viability but among the cells surviving the treatment, a HIV-1 reactivation can be observed as measured by increased RT activities depicted in cell supernatants or by the appearance of HIV-1 antigens inside cells. Singlet oxygen (1O2) when generated either in the cytoplasm or in the cell nucleus can also promote an important HIV 1 reactivation from treated cells. However, extracellular generation of 1O2 cannot trigger the HIV-1 reactivation although this kind of treatment is highly cytotoxic. These experiments demonstrate that different reactive oxygen species are able to lead to an intracellular pro-oxidant state initiating one or several signalling pathways which lead in fine to the HIV-1 LTR transactivation by regulatory proteins. PMID- 8194138 TI - Regulation of the transcription factors NF-kappa B and AP-1 by redox changes. AB - There is increasing evidence that reactive oxygen intermediates (ROIs) play an important role in cellular processes such as signal transduction and the control of gene expression. The activity of transcription factors like AP-1 and NF-kappa B is modulated by the redox state of the cell. NF-kappa B is activated by a prooxidant state in the cell and is therefore potentially inhibited by antioxidants. In contrast, AP-1 is strongly activated by antioxidants and shows reduced activity in the presence of oxidants. The antioxidant-mediated activation of AP-1 relies on the de novo synthesis of c-fos and c-jun mRNAs. Induction of c fos expression is primarily mediated by transcription factors binding to the SRE element in the c-fos promoter. Thus SRE binding factors can be considered as primary antioxidant response factors, while AP-1 itself is a secondary response factor. PMID- 8194139 TI - Effect of age on serum prolactin concentration in presumably fertile men in Sri Lanka. AB - OBJECTIVE: To examine possible age related variation in serum prolactin in men. DESIGN: A cross sectional study. SUBJECTS: Healthy married men aged 21 to 85 years with one or more children. MEASUREMENTS: Serum prolactin concentrations measured by immunoradiometric assay. RESULTS: Prolactin concentrations were significantly higher (p < 0.001) from 61 years of age onwards when compared with 31 to 60 years. Prolactin concentrations between 21 to 30 years were significantly higher than between 31 to 50 years (p < 0.05), but lower than between 61 to 70 (p < 0.05) and 75 to 85 (p < 0.01) years. CONCLUSIONS: Serum prolactin concentrations show age related variations in presumably fertile men. PMID- 8194141 TI - Subcutaneous morphine for postoperative analgesia. AB - OBJECTIVE: a. To confirm the efficacy of subcutaneous morphine infusion for postoperative analgesia and compare this effect with three-hourly subcutaneous bolus injections of morphine. b. To evaluate the suitability of a simple micro infusion set to deliver subcutaneous infusion, as conventional infusion pumps are expensive and not readily available. SETTING: Double blind, prospective controlled clinical trial. PATIENTS: 21 patients belonging to the American Society of Anaesthesiologists' (ASA) classes I or II, who underwent major elective abdominal surgery were studied in an intensive care unit. INTERVENTION: All patients were given loading doses of morphine intravenously (iv) followed by subcutaneous (sc) infusion in two groups and three-hourly sc bolus injections in the third group. The doses were titrated on an individual basis. The infusion was delivered by a power driven pump in one group and by a microinfusion set in the other. Those with significant pain during this regime were given morphine supplements intravenously. MEASUREMENT: Pain scoring was done hourly using a modified verbal rating scale. The percentage of patients who required intravenous supplements in each group was compared to draw statistical conclusions. RESULTS: 1. Subcutaneous infusion provided adequate analgesia in 86% of the patients studied. 2. There was no significant difference between the groups in terms of additional iv supplement requirement. 3. The microinfusion set required frequent readjustments to maintain constant flow. CONCLUSIONS: Intermittent subcutaneous bolus injections of morphine given through an indwelling butterfly needle is a simple, safe, and effective method for postoperative analgesia after major abdominal surgery. Simple infusion sets are not suitable to deliver subcutaneous infusions, and the need for infusion pumps makes the infusion technique unsuitable for routine use in wards. PMID- 8194142 TI - Prevalence of lipid abnormalities in Sri Lankan patients with non-insulin dependent diabetes mellitus. AB - OBJECTIVE: To determine the prevalence of hyperlipidaemia in Sri Lankan patients with non-insulin dependent diabetes mellitus (NIDDM) and a normal control population. DESIGN: A cross-sectional study. SETTING: Patients with NIDDM randomly selected from a diabetic clinic register and non-diabetic controls randomly selected from an electoral register. PATIENTS: 498 patients with NIDDM (197 females mean age 53.5, SD 6.2 years) and 253 non-diabetic controls (101 females, mean age 53, SD 5.5 years matched for age and sex. METHODS: Diabetes and impaired glucose tolerance (IGT) were excluded in the control group by a 75g oral glucose tolerance test. Total cholesterol, high density cholesterol and triglycerides were determined in fasting blood samples. RESULTS: The prevalence of lipid abnormalities was significantly higher in diabetic patients than in controls. The prevalence of hypercholesterolaemia was 21% vs 14% and that of hypertriglyceridaemia 16% vs 8.3%. Mean fasting blood glucose was higher (9.7 + 2.7) in hyperlipidaemic patients than in normolipidaemic diabetic patients (7.5 + 2.1) CONCLUSIONS: Hyperlipidaemias are common in Sri Lankan patients with NIDDM and screening for them should be an essential component of management of patients with diabetes mellitus. PMID- 8194140 TI - Incidence of induced abortion determined by the randomised response technique. AB - OBJECTIVE: To estimate the incidence of induced abortion using the randomised response technique, and to compare the results with estimates obtained by direct questioning. DESIGN: Cross-sectional study. SETTING: Medical Officer of Health area, Homagama. SUBJECTS: Married women in the reproductive age group. RESULTS: The annual incidence of induced abortion for the three year period 1988 to 1990 was 15.7 per 1000 married women of the reproductive age group as estimated by the randomised response technique. Direct questioning led to 30.5% under-reporting of induced abortion. The application of the method failed only in 8.1% of the population studied. CONCLUSIONS: The randomised response technique is a feasible method to use in our population and provides the best estimates of induced abortion. PMID- 8194143 TI - Agricultural accidents in north central Sri Lanka. PMID- 8194144 TI - The treatment of ulcerative colitis: from cure to a new disease. PMID- 8194145 TI - My impressions of Sri Lanka: criticism without offence. PMID- 8194146 TI - Pharmacological management of hypertension in pregnancy. PMID- 8194147 TI - Salmonella typhi endocarditis. AB - We report the case history of a patient with Salmonella typhi endocarditis. Bacteriological diagnosis was made by bone marrow culture when isolation from blood was unsuccessful. This is the first case of S typhi endocarditis to be documented in Sri Lanka. PMID- 8194148 TI - Sulphadoxine-pyrimethamine and chloroquine resistant Plasmodium falciparum infection in Sri Lanka. PMID- 8194149 TI - Acalypha indica induced haemolysis in G6PD deficiency. AB - Four patients who developed acute intravascular haemolysis after ingestion of a broth containing Acalypha indica (Sinhala: Kuppameniya) are reported. All four patients were found to have glucose-6-phosphate dehydrogenase deficiency. It is a common belief that ayurvedic medicines are free of side effects. Our report confirms again the fallacy of this belief. PMID- 8194150 TI - Skeletal fluorosis with neurological complications. AB - A case of skeletal fluorosis with spinal cord compression from Kekirawa following consumption of water with high fluoride content for about 20 years is described. The observations of other workers (4,5) and the present case report show that more extensive field studies among vulnerable populations is indicated in this region. The need to search for a cost effective method of defluoridation of water is stressed. PMID- 8194151 TI - Cystic fibrosis in Sri Lanka. PMID- 8194152 TI - Chronic haematoma of the anterior abdominal wall presenting as an obstructed ventral hernia. PMID- 8194154 TI - Benzathine penicillin for rheumatic fever prophylaxis. PMID- 8194153 TI - First-aid for jellyfish stings. PMID- 8194155 TI - Neurology of sleep. PMID- 8194156 TI - Phases and phase transitions of the glycoglycerolipids. AB - LIPIDAT is a computerized database providing access to the wealth of information scattered throughout the literature concerning synthetic and biologically derived polar lipid polymorphic and mesomorphic phase behavior. The database is considered comprehensive for glycerophospholipids, glycoglycerolipids, sphingolipids and natural membrane extracts. Here, a review of the LIPIDAT data subset referring to glycoglycerolipids is presented together with an analysis of these data. The glycoglycerolipids subset represents 4% of all LIPIDAT records. It includes data collected over a 20-year period and consists of 419 records obtained from 37 articles in 13 journals. An analysis of the data in the subset has allowed us to identify trends in hydrated glycoglycerolipids phase behavior reflecting differences in hydrocarbon chain length, chain branching, chain glycerol linkage type (ether vs. ester), sugar headgroup-glycerol linkage type (alpha vs. beta) and sugar headgroup identity. Included is a summary of the data concerning the effect of pH and of stereochemical purity on glycoglycerolipid phase behavior. Information on the mesomorphism of biologically derived and dry glycoglycerolipids is also presented. This review includes 92 references. PMID- 8194157 TI - Anthrylvinyl-labeled phospholipids as membrane probes: the phosphatidylcholine phosphatidylethanolamine system. AB - The phase behavior of mixtures of phosphatidylcholine (PC) with phosphatidylethanolamine (PE) identical or differing in their fatty acid composition has been investigated by using the steady-state fluorescence anisotropy of anthrylvinyl-labeled PC and PE (APC and APE) as well as of the non lipid probe 1,6-diphenyl-1,3,5-hexatriene (DPH) to detect temperature-dependent changes in multilayer liposomes. APC, but not APE, was able to detect the pretransition of dimyristoyl-PC. The phospholipid probes APC and APE showed the main phase transition of their unlabeled disaturated analogues at temperatures almost identical with those revealed by differential scanning calorimetry, whereas the onset of the PE phase transition recorded by DPH was several degrees higher. In PC-PE mixtures with high content of PE the phase transitions shown by APC and APE were broader than those recorded by DPH. Comparison of phase diagrams constructed on the basis of fluorescence anisotropy and calorimetric data led to the conclusion that in biphasic PE and PC-PE systems DPH tends to partition into solid regions, whereas the anthrylvinyl-labeled phospholipids distribute more evenly between coexisting phases or prefer fluid domains. The use of anthrylvinyl phospholipid probes made it possible to demonstrate that PEs and PCs identical in their fatty acids are not miscible completely, not only below but also well above Tm of the higher melting component. Generally, APC and APE fluorescence anisotropy measurements correctly reflect headgroup-dependent phase segregations in mixtures of PC with PE, but may lead to ambiguous conclusions if demixing is caused by differences in the hydrocarbon chains. PMID- 8194158 TI - FTIR study of lamellar and reversed micellar phases in the mono oleoylglycerol/water system. AB - The lamellar liquid crystalline (L alpha) and the reversed micellar (L2) phases of mono-oleoylglycerol (MO) in water were investigated by Fourier transform infrared (FTIR) spectroscopy. From polarized infrared spectra of aligned bilayers of MO/water, order parameters (S) were determined for vibrational modes in the hydrocarbon chain region (symmetric CH2 stretch and olefinic CH=CH stretch) and the aggregate surface region (C=O stretch and asymmetric CO-O-C stretch). The phase transition between L alpha and L2 (10 wt% water) occurs in the temperature range 43-46 degrees C. Already at about 32 degrees C the LD value for the C-OH stretching vibration has decreased to 50% of its value at 25 degrees C. A similar relative decrease in LD is obtained for the C=O stretch and the asymmetric CO-O-C stretch at about 38 degrees C and for the CH=CH stretch at about 43 degrees C. It is concluded that the molecular ordering in the region of the aggregate surface starts to decrease at a lower temperature than for the acyl chain region. Infrared spectra show a significant decrease in the conformational order of the hydrocarbon chains at the L alpha/L2 phase transition. PMID- 8194159 TI - Role of headgroup structure in the phase behaviour of N-acylethanolamine phospholipids: hydrogen-bonding ability and headgroup size. AB - The physical properties of aqueous dispersions of N-acylphosphatidylethanolamine from natural origin with long N-acyl chain (NAPE) and headgroup modified analogues have been studied. N-Acylation of PE causes a significant increase in the gel-to-liquid crystalline lamellar phase transition temperature in contrast with saturated N-acyl(dipalmitoyl) PEs, and in addition it does not restrict the headgroup rotational mobility in gel phase. The results agree with the increase of hydration of the phosphate group compared with that in PE and suggest the formation of hydrogen bonds between amide groups. The modifications introduced modulate the headgroup size and their hydrogen bonding capability. An increasing number of methylene groups between the phosphate and amide groups does not modify the phase behaviour observed. N-methylation of the amide group, which prevents the possibility of intermolecular hydrogen bond formation, decreases the melting temperature and the cooperativity of the phase transition and does not change the phase behaviour, while the hydration at the ester carbonyl groups level is decreased. On the other hand, the addition of N-ethyl substituent to the amide group or substitution of an ester group for this group increases its tendency to form structures with inverted geometries. The behaviour of these compounds suggests that hydration forces must be more important than considerations of the lipid dynamic shape in predicting the relative stabilities of lamellar vs. non lamellar phases for NAPEs with long saturated N-acyl chain. PMID- 8194160 TI - Interaction of the interdigitated DPPG or DPPG/DMPC bilayer with human erythrocyte band 3: differential scanning calorimetry and fluorescence studies. AB - Human erythrocyte band 3 reconstituted into phospholipid vesicles has been used for studying the interaction of interdigitated lipid bilayer with an integral membrane protein. The interdigitated gel phase in DPPG/band 3 or DPPG/DMPC/band 3 systems was induced with polymyxin B (PMB) or Tris+. The phase transitions of the vesicles were detected with high-sensitivity differential scanning calorimetry (DSC). The results indicated that band 3 does not cause significant alterations in the interdigitated phase of phospholipids, with only a little decrease of the phase transition enthalpies. Fluorescence measurements showed that the transition of phospholipid/band 3 systems from the non-interdigitated to interdigitated phase is accompanied by marked intrinsic fluorescence changes of band 3. The interdigitated phase of DPPG or DPPG/DMPC vesicles increases the intrinsic fluorescence intensity of band 3 and significantly decreases the accessibility of certain tryptophan residues on the protein to Cs+. PMID- 8194161 TI - In vitro characterization of the myelotoxicity of cyclopentenyl cytosine. AB - We studied the toxicity of a new experimental anticancer drug, cyclopentenyl cytosine (CPE-C), to human and murine hematopoietic progenitor cells in vitro. Due to CPE-C's in vivo myelotoxicity, it was important to characterize its potential adverse effects on human marrow cells during preclinical development of the drug. Marrow cells were exposed to CPE-C for either 1 h prior to addition in clonal assays or continuously during their culture period. The inhibitory effects of CPE-C on myeloid (CFU-gm) and erythroid (CFU-e, BFU-e) colony formation were concentration- and time-dependent, with continuous CPE-C exposure being significantly more inhibitory than 1-h exposure. The results of both exposure experiments were combined to investigate colony inhibition as a function of overall drug exposure (concentration x time, AUC) and data analyzed by the nonlinear Emax equation. Human and murine CFU-gm had similar AUC-response curves and IAUC70 values (i.e., AUC at 70% colony inhibition) of 40.8 and 41.9 microM h, respectively. In contrast, murine CFU-e and BFU-e were more sensitive to CPE-C, having lower IAUC70 values (both, 21.1 microM h) than human CFU-e and BFU-e (107.8 and 33.0 microM h, respectively). This difference was most prominent with the late erythroid progenitor, CFU-e, in that the human cells were 5 times more resistant to inhibition by CPE-C. CPE-C was myelotoxic in vitro to human and murine marrow cells and toxicity correlated with overall drug exposure. PMID- 8194162 TI - Cellular pharmacology of the partially non-cross-resistant anthracycline annamycin entrapped in liposomes in KB and KB-V1 cells. AB - The in vitro cytotoxicity, cellular pharmacology, and DNA lesions induced by the lipophilic anthracycline annamycin (Ann) were studied in KB and KB-V1 (multidrug resistant) cells. Ann was tested in suspension in saline and 10% dimethylsulfoxide (DMSO: final concentration, 0.05%-0.5%) or entrapped in multilamellar liposomes (median size, 1.57 microns). Doxorubicin (Dox) was about twice as cytotoxic as Ann or liposome-entrapped Ann (L-Ann) against KB cells. Both Ann and L-Ann displayed a partial lack of cross-resistance with Dox (resistance indices: > 60 for Dox, 4.7 for Ann, 4.0 for L-Ann). Accumulation of Ann in KB and KB-V1 cells was consistently about 2-3 and 10-20 times higher, respectively, than that of Dox. Cellular retention of Ann in KB and KB-V1 cells was about 2 and 30 times higher, respectively, than that of Dox as a result of the different efflux patterns of the two drugs: Dox was not effluxed from KB cells but was significantly effluxed from KB-V1 cells (66% at 1 h, whereas Ann efflux was similar in both cell lines (about 50% at 1 h). Dox retention in KB-V1 cells was increased by a factor of 2 in the presence of verapamil or cyclosporine A, but Ann retention was not. In addition, accumulation of Dox in KB-V1 cells was enhanced by the metabolic inhibitor deoxyglucose/azide and the membrane carboxylic ionophore monensin, whereas accumulation of Ann was not affected by either agent. All these findings indicate significant differences in the cellular transmembrane transport systems between Dox and Ann and suggest that Ann efflux is not mediated by P-glycoprotein. Liposome entrapment reduced by a factor of 1.3 2.0 the cellular accumulation of Ann without affecting its cytotoxicity. As compared with Dox, both Ann and L-Ann induced 3 times more DNA double- and single strand breaks in KB cells. In KB-V1 cells, Dox did not induce DNA damage, whereas the extent of DNA breaks induced by both Ann and L-Ann was similar to that induced by Dox in KB cells. Our results indicate (1) that the lack of cross resistance between Ann and Dox is associated with a markedly enhanced accumulation and retention of Ann in KB-V1 cells and (2) that the type of liposomes used does not significantly affect the cellular effects of Ann. PMID- 8194163 TI - Renal and hepatic toxicity after high-dose 7-hydroxymethotrexate in the rat. AB - To examine directly the hepatic and renal toxicity of 7-hydroxymethotrexate (7-OH MTX) without interference of the parent compound methotrexate (MTX), we purified and gave 100 mg/kg 7-OH-MTX to rats, a dose resulting in serum levels of 7-OH-MTX comparable with those achieved in the clinic after the administration of high dose MTX (HD-MTX). After only 5 h, the 7-OH-MTX-treated rats demonstrated 2.6 fold increases in serum creatinine values and 2-fold elevations in serum aspartate aminotransferase (ASAT) levels as compared with the controls. Morphologic evidence of toxicity, however, was apparent only in the kidneys. Intraluminal cellular debris containing membranous material and deteriorated organelles was seen, but no precipitate of the delivered drug. The peak serum concentration of 7-OH was up to 939 microM, and concentrations of 7-OH-MTX declined triphasically, showing a t1/2 alpha value of 2.45 min, a t1/2 beta value of 30.5 min, and a terminal half-life (t1/2 gamma) of 240 min. The total clearance value was 14.5 ml min-1 kg, and the postdistributional volume of distribution (V beta) was 5070 ml/kg. Our results may indicate a direct toxic effect of 7-OH-MTX on kidney and liver cells. PMID- 8194164 TI - Transfer of liposomal drug carriers from the blood to the peritoneal cavity of normal and ascitic tumor-bearing mice. AB - Previously we have demonstrated that the L1210 antitumor activity of liposomal doxorubicin increased significantly as the size of the liposomal carrier was reduced from 1.0 to 0.1 micron. It is demonstrated herein that empty and drug loaded small (0.1-micron diameter) liposomes accumulate efficiently into the peritoneal cavity of normal and ascitic L1210 tumor-bearing animals following i.v. administration. In normal mice injected with 100 nm DSPC/chol liposomal doxorubicin (drug-to-lipid ratio of 0.2; wt/wt) approximately 2.8 micrograms drug could be recovered from the peritoneal cavity following peritoneal lavage at 24 h. Although this represents only 0.7% of the injected doxorubicin dose, this level of drug is 2 orders of magnitude greater than that achieved following administration of an equivalent dose of free drug (20 mg/kg). The drug levels achieved within the peritoneal cavity are dependent on the physical characteristics (size, drug-to-lipid ratio and lipid composition) of the liposomes employed. Optimal delivery is obtained employing 100 nm DSPC/chol liposomal doxorubicin, a vesicle system that is known to retain entrapped drug following i.v. administration and exhibits extended circulation lifetimes. Analysis of drug and liposome distribution within the peritoneal cavity of normal mice indicates that as much as 50% of the measured doxorubicin and liposomal lipid is cell-associated. Flow cytometric analysis of the peritoneal cells demonstrated that cell-associated doxorubicin resides almost exclusively within resident peritoneal macrophages. The increased delivery of doxorubicin to the peritoneal cavity of normal mice following i.v. administration of small (0.1 micron) liposomal doxorubicin is correlated with a pronounced (> 90%) and prolonged (> 14-day) suppression of resident peritoneal cells. Liposomal drug accumulation increased dramatically in animals with an established L1210 ascitic tumor. More than 5% of the injected dose was found in the peritoneal cavity of these animals 24 h after treatment with DSPC/chol liposomal doxorubicin as compared with a value of 0.03% of the injected dose achieved with free drug. It is proposed that accumulation of liposomes into the peritoneal cavity of normal and tumor-bearing mice may serve as a useful model for characterizing factors mediating the transfer of liposomes from the vascular compartment to extravascular sites. PMID- 8194165 TI - Inhibition of dihydropyrimidine dehydrogenase by alpha-interferon: experimental data on human tumor cell lines. AB - Interferons (IFNs) are very promising fluorouracil (FU) biochemical modulators. The pharmacological origin sustaining the FU-IFN synergistic interaction is not clearly understood. It was recently shown that alpha-IFN was associated with a dose-dependent decrease in FU clearance in treated patients. Dihydropyrimidine dehydrogenase (DPD) is the key regulating enzyme for FU catabolism. The effects on DPD exerted by both the IFN dose and the duration of exposure were evaluated in a panel of five human cancer cell lines. All cell lines investigated exhibited quantifiable DPD activity with inter-cell-line variability (0.118-0.318 nmol min 1 mg protein-1). A prolonged exposure to IFN (up to 5 days) was necessary to obtain a significant inhibition of DPD activity. A concentration-dependent significant decrease in DPD activity, reaching 50% of the initial activity determined for the highest IFN concentration (10(5) IU/ml), was demonstrated in all cell lines tested (5-day IFN exposure). For three cell lines, IFN potentiated the FU-induced growth inhibition in a concentration-dependent manner. Considering all cell lines and all IFN concentrations, it appears that globally, the greater the inhibition of DPD activity, the greater the FU potentiation (Spearman rank correlation on all cell lines, P = 0.011). PMID- 8194166 TI - Effect of DNA-repair-enzyme modulators on cytotoxicity of L-phenylalanine mustard and cis-diamminedichloroplatinum (II) in mammary carcinoma cells resistant to alkylating drugs. AB - We investigated the effect of DNA-repair-enzyme inhibitors on L-phenylalanine mustard (L-PAM) and cis-diamminedichloroplatinum (II) (CDDP) cytotoxicity in rat mammary-carcinoma MatB cells sensitive (WT) and resistant (MLNr) to bifunctional alkylating drugs. Among the modulators tested, the combination of arabinofuranosylcytosine (Ara-C) and hydroxyurea (HU) significantly increased the sensitivity of the cells to CDDP and, to a lesser extent, L-PAM as compared with cells treated with drug alone. The modulation effect of HU+Ara-C on CDDP and L PAM cytotoxicity was more effective when intracellular glutathione (GSH) was depleted by L-buthionine-(S,R)-sulfoximine (BSO). This was also associated with a significant increase in DNA-DNA interstrand cross-links. Caffeine also sensitized both WT and MLNr cells to the cytotoxic effect of L-PAM and CDDP, and this effect was potentiated in GSH-depleted cells. No significant effect was observed with other repair modulators such as aphidicolin, 3-aminobenzamide, novobiocin, or etoposide. These results show (a) that inhibition of DNA repair by HU+Ara-C or caffeine could be a target for modulation of bifunctional alkylating-drug resistance and (b) that GSH depletion renders resistant cells more susceptible to the repair-enzyme modulators, suggesting that intracellular GSH may be involved in the regulation of some of these enzymes. Our results also indicate that a combination of a number of modulators may offer an advantage over the use of a single modulator in tumor resistance that may be associated with multifactorial mechanisms. PMID- 8194167 TI - Novel carbamate analogues of amsacrine with activity against non-cycling murine and human tumour cells. AB - The cytotoxicity of a class of compounds related to the topoisomerase-II poison amsacrine was investigated against plateau-phase murine Lewis lung carcinoma cells (LLTC), HCT-8 human colon carcinoma cells and other cell lines. Methyl N-[4 (9-acridinylamino)-2-methoxy-phenyl]carbamate hydrochloride and the corresponding demethoxy compound, which contain a methylcarbamate instead of the methylsulphonylamino group, manifested relatively high cytotoxic activity against plateau-phase cells as measured by clonogenic survival. The concentration of drug required for a given cytotoxic effect on plateau-phase cells was about 2 times higher than that required for an equitoxic effect on actively proliferating cells. In contrast, at least 5 times more amsacrine, doxorubicin or etoposide was needed for an equitoxic effect on plateau-phase cells. Cells taken directly from subcutaneous LLTC tumours and exposed to drugs displayed the same differential drug sensitivity to the carbamate compounds, suggesting that the plateau-phase cells provide an appropriate model for cells growing in vivo. The greater cytotoxicity of the carbamate drugs was shown to depend critically on the provision of an energy source such as glucose, suggesting that nutrient starvation both in plateau-phase cells and in tumours induced a glucose-sensitive resistance mechanism. It is suggested that the carbamate analogues of amsacrine recognize a form of topoisomerase II, possibly topoisomerase II beta, the activity of which increases relative to that of topoisomerase II alpha in non cycling cells, and might be used to devise new strategies for the treatment of solid tumours. PMID- 8194168 TI - Bullatacin--in vivo and in vitro experience in an ovarian cancer model. AB - The cytotoxicity and antitumor effects of the acetogenin Bullatacin were evaluated in vitro in multiple ovarian cancer cell lines and in vivo in a murine ovarian teratocarcinoma (MOT) model in C3HeB/FeJ mice. The in vitro cytotoxicity of Bullatacin against four human ovarian epithelial tumor cell lines (OC-194, OC 222, OVCAR-3, and A-2780) was assessed in 48- and 72-h tetrazolium-dye (MTT) cytotoxicity assays. The percentage of cytotoxicity was determined on the basis of the mean optical density of the respective untreated cells and the dose effective against 50% of the cells (ED50) was calculated for each cell line. In vivo experiments were performed on adult female C3HeB/FeJ mice, which were injected i.p. with 10(5) MOT cells and varying amounts of Bullatacin given either in a single dose or in 5 subsequent doses over 72 h. All mice were observed for survival relative to that of the control groups, which were injected either with 10(5) MOT cells with or without serial injections of vehicle or with vehicle only. All four epithelial ovarian cancer cell lines displayed sensitivity to Bullatacin. The relative cytotoxic effects were very heterogeneous, with the ED50 value ranging between 10(-7) micrograms/ml for OC-194 and 4 micrograms/ml for the cisplatin-resistant cell line OVCAR-3 in a 72-h MTT cytotoxicity assay. All mice that had been injected i.p. with 10(5) MOT cells and 1.4 mg/kg or more of Bullatacin died within the first 24 h after injection, whereas all mice that had received 600 micrograms/kg of Bullatacin or less survived equally as long as the controls that had been injected with MOT only (21.1 +/- 0.9 days). Mice that had received Bullatacin at a dose ranging from 600 micrograms/kg to 1.4 mg/kg either died during the 1st day postinjection or survived, but not longer than the MOT control group. Serial i.p. injections of Bullatacin again either led to death of the mice within 24-48 h of the last dose of Bullatacin or did not have any effect on the survival of the mice as compared with the respective control groups, which had been injected with the tumor and serial injections of vehicle (22.5 +/- 2.2 days). In summary, Bullatacin showed no effect on MOT-caused animal death in C3HeB/FeJ mice at nonlethal dose ranges, whether it was given as a single i.p. dose or serially over 72 h. In vitro, however, it proved to be a very potent cytotoxic agent in a variety of ovarian cancer cell lines.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8194169 TI - Activity of 9-dimethylaminomethyl-10-hydroxycamptothecin against pediatric and adult central nervous system tumor xenografts. AB - The activity of dimethylaminomethyl-10-hydroxycamptothecin (topotecan) was evaluated against a panel of xenografts derived from ependymomas (D528 EP, D612 EP), childhood high-grade gliomas (D-456 MG, D-212 MG), adult high-grade gliomas (D-245 MG, D-54 MG), and medulloblastomas (D425 Med) growing s.c. and i.c. (intracranially) in athymic nude mice. Topotecan was given at a dose of 1.9 mg/kg by i.p. injection in 0.9% saline using a volume of 90 ml/m2 on days 1-5 and 8-12, which represents the dose lethal to 10% of treated animals. Topotecan was active in the therapy of all s.c. xenografts tested, with growth delays ranging from 6.3 days in D-54 MG to 55.7 days in D528 EP. Topotecan produced statistically significant tumor regressions in D425 Med, D-456 MG, D-245 MG, D528 EP, and D612 EP. No tumor regression was seen in any control animal. Statistically significant increases in median survival were seen in the two i.c. xenografts--D-456 MG (28.6% increase) and D-54 MG (39% increase)--treated with topotecan. These studies suggest that topotecan may be an important new addition to the therapy of central nervous system tumors. PMID- 8194170 TI - Etoposide-related acral erythema. PMID- 8194171 TI - The importance of tamoxifen metabolism in tamoxifen-stimulated breast tumor growth. AB - The acquired ability of tamoxifen to stimulate tumor growth has been suggested as one mechanism for the development of treatment failure in breast cancer. We have reported that tamoxifen-stimulated MCF-7 breast tumors in nude mice display reduced tamoxifen levels as compared with tamoxifen-inhibited tumors and an altered metabolite profile with isomerization of trans-4-hydroxytamoxifen to a weak antiestrogen and the production of metabolite E, an estrogenic metabolite. To investigate further the importance of tamoxifen metabolism in this model, we quantified levels of tamoxifen and major metabolites in tamoxifen-stimulated as compared with tamoxifen-inhibited MCF-7 tumors growing in nude mice and employed tamoxifen analogs resistant to metabolism. Tamoxifen-stimulated tumors have a relative abundance of cis-4-hydroxytamoxifen and metabolite E. However, in vivo treatment of mice carrying tamoxifen-stimulated tumors with fixed-ring nonisomerizable tamoxifen analogs or with nafoxidine, a nonsteroidal antiestrogen with a different structure, nonetheless resulted in tumor growth stimulation. Tumors were also stimulated by a deoxytamoxifen analog resistant to conversion to metabolite E. Growth of tamoxifen-stimulated tumors was inhibited by a pure steroidal antiestrogen, ICI 182,780, suggesting the need for clinical trials of this drug in patients with tamoxifen resistance. Growth of tamoxifen-stimulated tumors was further stimulated by estrogen replenishment, and this estrogen stimulation could be blocked by tamoxifen indicating that tamoxifen has both agonist and antagonist properties in these tumors. This study suggests that tamoxifen-stimulated tumor growth in this model is not due to isomerization or metabolism of tamoxifen to less antiestrogenic or more estrogenic metabolites. The mechanisms by which tamoxifen acquires more potent in vivo agonist properties, resulting in tumor growth stimulation over time, remain to be defined. PMID- 8194172 TI - Reversal of the human and murine multidrug-resistance phenotype with megestrol acetate. AB - MA is an orally active PG derivative with an excellent safety profile that is used primarily for the treatment of carcinomas of the breast and endometrium. We investigated the potential application of MA as an MDR-reversal agent using cell culture and human tumor xenograft models. The reversing activity of MA in vitro was compared with that of PG and VER in two human MDR cell lines, the colon carcinoma HCT-116/VM46 and the breast carcinoma MCF-7/ADR, and in a murine cell line, J774.2. At concentrations as low as 3 microM, MA was capable of partially restoring sensitivity to Act D in the HCT-116/VM46 cells and sensitivity to DOX in the MCF-7/ADR cells. Although less effective than VER, MA was about 2.5 times more potent than PG in reversing MDR at equimolar concentrations. Increased accumulation of DOX in drug-resistant cells that were treated simultaneously with MA was observed by flow cytometry. In vivo, using established human colon and breast carcinoma xenografts implanted s.c. in athymic mice, the combined therapy with MA and DOX resulted in enhanced antitumor activity relative to that of DOX alone in the MDR sublines. These results suggest that MA may be a promising clinical MDR-reversing agent. PMID- 8194173 TI - A woman with amenorrhea and galactorrhea. PMID- 8194174 TI - Common complications and emergencies associated with cancer and its therapy. AB - BACKGROUND: As the incidence of cancer rises and as physicians treat it more aggressively, more patients will experience complications of cancer or of its therapy. OBJECTIVE: To review the pathogenesis, diagnosis, and treatment of the superior vena cava syndrome, malignant pericardial effusions, the syndrome of inappropriate antidiuretic hormone secretion, hypercalcemia, the tumor lysis syndrome, seizures, spinal cord compression, obstructive uropathy, infections, febrile neutropenia, bleeding, thrombocytopenia, and coagulopathies in patients with cancer. SUMMARY: In general, the best treatment for most of the complications of cancer is to successfully treat the cancer itself; if this is not feasible, palliative measures should be taken. The complications of treatment are well known and should be treated promptly when they arise if they cannot be prevented. CONCLUSIONS: Although treating the complications associated with cancer cannot always prolong the patient's life, it frequently can improve the quality of life remaining. Therefore, physicians who care for patients with cancer should anticipate these complications and treat them promptly when they occur. PMID- 8194175 TI - The search for diagnostic criteria in Alzheimer's disease: an update. AB - BACKGROUND: Although the pathologic findings in Alzheimer's disease are well documented, definitive diagnostic criteria are lacking. OBJECTIVE: To review the histopathologic findings in Alzheimer's disease. SUMMARY: In Alzheimer's disease, the brain may be normal in size or atrophic. There is selective neuronal loss associated with neurofibrillary tangles and senile plaques with amyloid deposits. Amyloid protein may also be deposited within arterioles. There may be granulovacuolar degeneration and Hirano bodies in the hippocampus. Two diagnostic schemes have been proposed based on the presence of senile plaques, but neither is entirely satisfactory. CONCLUSIONS: The pathologic diagnosis is usually made in conjunction with the clinical history. Probably, neither definitive diagnostic criteria nor effective treatment for Alzheimer's disease will be possible until we understand more about its etiology. Clinicians should attempt to rule out other, potentially curable causes of dementia in elderly patients such as trauma, depression, metabolic abnormalities, infection, vascular disease, and other central nervous system diseases. PMID- 8194176 TI - Dilate or debulk? PMID- 8194177 TI - Pleural changes in malignant pleural effusions: appearance on computed tomography. AB - BACKGROUND: Tumors metastatic to the pleura are a leading cause of pleural effusions. The computed tomographic (CT) appearance of malignant pleural effusions varies from uniformly low attenuation without pleural abnormalities to thickened, irregular, contrast-enhanced pleura with or without discrete masses. There may be associated changes in the subcostal tissues. OBJECTIVE: To determine the prevalence of abnormalities observed with CT scanning in patients with malignant pleural effusion. METHODS: We analyzed the CT appearance of the pleura in 86 patients with documented malignant pleural effusions. Patients with primary malignancy of the pleura (mesothelioma) were excluded. RESULTS: In 98% of the malignant effusions the fluid was homogeneous. Focal tumor masses were identified within the effusion in 10%. CT evidence of fluid loculation was seen in 40%. Pleural thickening, either smooth or irregular, was identified in 62%. CONCLUSIONS: The transaxial anatomic display afforded by CT scanning facilitates demonstration of several features that should arouse the suspicion of the radiologist and the clinician to the possibility of malignancy involving the pleura. PMID- 8194178 TI - Attitudes toward childbearing and changes in sexual and contraceptive practices among HIV-infected women. AB - BACKGROUND: Women now constitute 12% of persons with acquired immunodeficiency syndrome (AIDS), and three quarters of them are well within their childbearing age. OBJECTIVE: To determine if women infected with human immunodeficiency virus (HIV) change their attitudes toward childbearing and their sexual and contraceptive practices. METHODS: Questionnaire and interview. RESULTS: Forty-six women age 18 to 44 participated; 33 were white, 12 were Hispanic, and 1 was black. Intravenous drug abuse was reported by 65%. Nineteen had symptomatic HIV disease or AIDS. Only 70% said they had received counseling after testing. Of these, 59% said they were counseled on avoiding pregnancy, and 81% said they were counseled on use of condoms. Before testing, 59% had wanted to have children; after testing, only 17% did. Only 4% said they had always used condoms before testing, but 54% said they did after testing; 39% said they used some form of birth control before testing compared with 70% who said they did after testing. CONCLUSIONS: Counseling was not optimal. Sexual and contraceptive practices changed, but follow-up study will be needed to see if such changes are sustained. PMID- 8194179 TI - Autologous blood transfusion and intraoperative cell salvage in a patient with homozygous sickle cell disease. AB - BACKGROUND: Autologous transfusion can eliminate the need for homologous transfusions. In addition, hypotensive anesthesia and devices that salvage red blood cells for return to the patient can reduce operative blood loss. However, blood from patients with sickle cell disease is difficult to store. SUMMARY: A 16 year-old black girl with homozygous sickle cell disease needed surgery for progressive scoliosis. Her family's religious convictions precluded homologous transfusions. During surgery, 400 mL of autologous blood that had been successfully stored was transfused, as was 800 mL of blood salvaged using a cell saving device, and 3800 mL of nonblood plasma expanders. Intravenous agents were used to maintain hypotension. However, following a rise in the patient's prothrombin and thromboplastin times, four units of homologous packed red cells were transfused with the permission of the patient's parents. CONCLUSIONS: Patients with sickle cell disease can be given hypotensive anesthesia and autologous transfusions of blood donated before surgery and blood salvaged during surgery using a cell-saving device. PMID- 8194180 TI - Congestive heart failure due to a pancreatic pseudocyst. AB - BACKGROUND: Mediastinal extension of pancreatic pseudocysts has caused rare cases of cardiac compression, but to our knowledge, congestive heart disease due to cardiac compression by a pancreatic pseudocyst has never been reported. SUMMARY: A 48-year-old man presented with dyspnea, swelling of both lower limbs, left sided chest pain, and colicky, nonradiating epigastric pain. Computed tomography of the abdomen and lower thorax revealed a huge cystic mass directly behind the heart, extending through the esophageal hiatus into the abdomen. The patient subsequently noted dysphagia and epigastric pain and began vomiting after meals. Radiography of the upper gastrointestinal system with barium contrast confirmed that the lower end of the esophagus and the right and lower portions of the stomach were extrinsically compressed. Complete recovery followed surgical removal and internal drainage of a large pancreatic pseudocyst. CONCLUSIONS: Mediastinal extension of a pancreatic pseudocyst can cause cardiac compression, leading to congestive heart failure. PMID- 8194182 TI - Influencing health behavior: physicians as agents of change. PMID- 8194181 TI - Right pleural effusion due to a migrating ventriculoperitoneal shunt. AB - BACKGROUND: Pseudotumor cerebri or benign intracranial hypertension is a collection of disorders characterized by papilledema and increased intracranial pressure without associated neurologic abnormalities and wherein the cerebrospinal fluid composition is normal. Therapy may consist of diuretics, acetazolamide, and, in more severe cases, ventricular shunts. SUMMARY: A patient with pseudotumor cerebri and a ventriculoperitoneal shunt presented with dyspnea early in her pregnancy. Chest roentgenography revealed a right pleural effusion and a shunt catheter in the right pleural space. The patient underwent four thoracenteses, and a new shunt was placed after the baby was born. CONCLUSIONS: Physicians should recognize the potential for a ventriculoperitoneal shunt to migrate from the peritoneum to the pleural space. In a pregnant patient, it is reasonable to perform serial thoracenteses as a temporizing measure, and the shunt can be definitively revised in an elective surgical procedure postpartum. PMID- 8194183 TI - Dr. John Phillips: the unknown physician. PMID- 8194184 TI - The maze procedure for refractory atrial fibrillation. PMID- 8194185 TI - Thromboembolic disease: underdiagnosed, undertreated, deadly. PMID- 8194186 TI - Managed care: the dark side. PMID- 8194187 TI - N1 component derived from the temporal region during an auditory passive event related potential paradigm in schizophrenics. AB - Event-related potentials (ERPs) were recorded at the Cz, W1 (Wernicke's area), and W2 (contralateral to Wernicke's) regions in 27 schizophrenics during an auditory passive sequence paradigm similar to that employed by Polich. N1 component for frequent tones was analyzed. In schizophrenics, the difference between the ERP waveforms at W1 and W2 was larger than that in controls, and N1 latency at W1 was significantly shorter than that at W2. To examine the similarity between interhemispheric waveforms, Person product-moment correlation coefficient (Interhemispheric Correlation Coefficient, IHCC) was calculated, time point by time point, between the ERP waveforms at W1 and at W2. The mean IHCC for schizophrenics was significantly lower than that for controls. In schizophrenics, the low IHCC group had more severe psychopathology and a longer duration of illness. These results suggest that the hemispheric imbalance of the temporal lobe is characteristic of schizophrenia. PMID- 8194188 TI - Epileptic syndromes in children with somatosensory evoked spikes. AB - We studied 186 children with frequent EEG paroxysms evoked by tapping of the feet or hands (ES). Seventy-five (40.3%) patients had a history of epileptic seizures. Febrile convulsions alone occurred in 31 (16.7%) of the children and nonfebrile in 44 cases (23.7%). Non-febrile seizures occurred in a greater proportion among patients with ES than in a control group with normal EEG. Spontaneous epileptiform activity was recorded in 39.6% of the patients without epileptic seizures but in a great percentage of the children with seizures (85.3%). The non febrile seizures were partial in 26 cases and generalized in 18. In 39 of these cases the EEG also showed spontaneous focal spikes, which occurred predominantly in the parietal regions in 24 cases. ES were observed in different types of partial and generalized epilepsies of childhood. Our findings also suggest that in an important proportion of cases there is a benign condition of a functional nature that is age-dependent, involving mainly the parietal lobe but in which seizure type does not so easily permit definition as a clearly characterized epileptic entity compared to other recognized idiopathic partial childhood epilepsies. PMID- 8194189 TI - Multiple sleep latency tests in epilepsy. AB - Seizure patients often complain of sleepiness or disturbed sleep. Although susceptible of medication effect, the multiple sleep latency test (MSLT) may quantify daytime sleepiness and help to establish whether qualitative sleep disturbance accompanies epilepsy. In order to measure daytime sleepiness in epilepsy patients, 30 patients with newly diagnosed or presently untreated complex partial seizures had MSLT after an overnight sleep EEG that showed no sleep deprivation or nocturnal seizures. Four 20-minute naps were undertaken at 09:00, 11:00, 13:00, and 15:00, and sleep latency was recorded along with 8 channels of EEG. Twenty of 30 seizure patients reported subjective sleepiness. Eight patients had average sleep latencies less than 8 minutes, and 3 had latencies less than 5 minutes. No sleep onset REM or respiratory disturbance was noted. Twenty-five patients had EEG abnormalities but none had ictal seizures. Right temporal epileptiform activity correlated with sleepiness. MSLT may quantify sleepiness in epilepsy patients, which is common but may be subjective or psychophysiological. Some patients with partial seizures have persistent daytime sleepiness independent of medication, possibly related to residual medication effects or non-specific effect of their epileptogenic foci. PMID- 8194190 TI - Persistent topographic quantitative EEG sequelae of chronic marihuana use: a replication study and initial discriminant function analysis. AB - In a previous pilot study using psychiatric patients we reported that daily marihuana users had significant elevations of (1) Absolute Alpha Power, (2) Relative Alpha Power, and (3) Interhemispheric Alpha Coherence over both frontal and frontal-central areas when contrasted with subjects who did not use marihuana. We referred to this phenomenon as Hyperfrontality of Alpha. The study presented here is a successful replication of our previous findings using new samples of subjects and identical methods. Post hoc analyses based on the combined sample from both studies suggest that variables of psychiatric diagnoses and medication did not bias our results. In addition, a discriminant function analysis using quantitative EEG variables as candidate predictors generated a 95% correct THC user versus nonuser classification accuracy which received a successful jackknife replication. PMID- 8194191 TI - The significance of amplitude asymmetry in clinical electroencephalography. AB - Forty-two EEG recordings with bilateral generalized slow background activity, but asymmetric because of suppression of the amplitude over one hemisphere, were selected for the study. This pattern was prospectively correlated with neurological findings as well as neuroimaging techniques. In 76% of cases, the suppression of the amplitude could be lateralized correctly to the site of cerebral insult. It is suggested that: (a) unilateral attenuation of the amplitude of the background EEG correlates highly with ipsilateral focal cerebral acute or subacute large lesion; (b) in cases where bihemispheric slow activity is present, the hemisphere with the lower amplitude is likely to be the site of such a structural lesion; and (c) this study also supports a previous report that amplitude depression has the same pathophysiological significance in EEG as delta activity. PMID- 8194192 TI - Gender differences in quantitative EEG at rest and during photic stimulation in normal young adults. AB - In the present study quantitative EEG analysis was performed in 20 male and 20 female healthy adults in order to examine the gender differences in EEG activity at rest and during photic stimulation. The females generally showed a higher amplitude in the resting EEG than the males, with significant differences observed for the delta, theta, alpha 2 and beta bands at the limited electrode sites. The gender differences were more pronounced in EEG activity during photic stimulation, and the females had a higher EEG amplitude in the frequency band identical or harmonically related to the stimulus frequency. These findings provide further evidence that the gender differences exist in EEG activity in both stimulus and nonstimulus conditions. PMID- 8194194 TI - 1 alpha,25-Dihydroxyvitamin D3 inhibits the invasive potential of human breast cancer cells in vitro. AB - Using the Boyden chamber invasion assay, the effect of 1 alpha,25 dihydroxyvitamin D3 [1 apha,25(OH)2D3] on the invasiveness of the highly invasive, oestrogen receptor-negative human breast cancer cell line MDA-MB-231 was examined. The MDA-MB-231 cells were shown to contain high-affinity receptors for 1 alpha,25(OH)2D3 with a Kd of 1.5 x 10(-11) M. When the cells were treated with 1 alpha,25(OH)2D3 for 4 days before the assay was performed, a dose dependent inhibition of their invasive potential was demonstrated. Fifty per cent inhibition of invasion was obtained with a concentration of 13 pM of 1 alpha,25(OH)2D3. However, when the cells were treated for only 6 h during the assay, no inhibitory effect was seen. The process of migration was also affected by treatment with 1 alpha,25(OH)2D3 for 4 days, although the inhibition was not of the same magnitude as seen for the invasion. Fifty per cent inhibition of migration occurred at a concentration of 3.2 nM of 1 alpha,25(OH)2D3 (250 times higher than in the invasion assay). Inhibition of invasion and migration was not due to the known anti-proliferative effect of 1 alpha,25(OH)2D3, as no growth reduction could be demonstrated with treatment up to 5 days. Based on the present investigation it can therefore be concluded that 1 alpha,25(OH)2D3 is able to inhibit tumour cell invasiveness by a mechanism which is not exclusively based on its anti-proliferative and anti-migrative effects. PMID- 8194193 TI - Oncogene-induced basement membrane invasiveness in human mammary epithelial cells. AB - Expression of the intermediate filament protein vimentin, and loss of the cellular adhesion protein uvomorulin (E-cadherin) have been associated with increased invasiveness of established human breast cancer cell lines in vitro and in vivo. In the current study, we have further examined these relationships in oncogenically transformed human mammary epithelial cells. A normal human mammary epithelial strain, termed 184, was previously immortalized with benzo[a]pyrene, and two distinct sublines were derived (A1N4 and 184B5). These sublines were infected with retroviral vectors containing a single or two oncogenes of the nuclear, cytoplasmic, and plasma membrane-associated type (v-rasH, v-rasKi, v mos, SV40T and c-myc). All infectants have been previously shown to exhibit some aspects of phenotypic transformation. In the current study, cellular invasiveness was determined in vitro using Matrigel, a reconstituted basement membrane extract. Lineage-specific differences were observed with respect to low constitutive invasiveness and invasive changes after infection with ras, despite similar ras-induced transformation of each line. Major effects on cellular invasiveness were observed after infection of the cells with two different oncogenes (v-rasH + SV40T and v-rasH + v-mos). In contrast, the effects of single oncogenes were only modest or negligible. All oncogenic infectants demonstrated increased attachment to laminin, but altered secretion of the 72 kDa and 92 kDa gelatinases was not associated with any aspect of malignant progression. Each of the two highly invasive double oncogene transformants were vimentin-positive and uvomorulin-negative, a phenotype indicative of the epithelial-mesenchymal transition (EMT) previously associated with invasiveness of established human breast cancer cell lines. Weakly invasive untransformed mammary epithelial cells in this study were positive for both vimentin and uvomorulin, suggesting that uvomorulin may over-ride the otherwise vimentin-associated invasiveness. PMID- 8194195 TI - Cell surface laminin-like substances and laminin-related carbohydrates of rat ascites hepatoma AH7974 and its variants with different lung-colonizing potential. AB - Rat ascites hepatoma AH7974 cells strongly expressed antilaminin antibody reactive substances (laminin-like substances) and Griffonia simplicifolia isolectin B4 (GS)-reactive carbohydrate (alpha-D-galactose; alpha-Gal) on their cell surface. The alpha-Gal expression was not apparently influenced by the pretreatment of cells with methanol. The cell membrane laminin-like substances has approximate molecular weights of 150, 62 and 56 kDa in denaturating reducing conditions, of which the 62 and 56 kDa bands were stained with GS. The cell membrane molecules bearing alpha-Gal were 62 and 56 kDa and were stained with antilaminin antibody. Therefore, the major molecules bearing alpha-Gal residues of AH7974 cell membrane are considered to be laminin-like substances. To determine the role of the substances in metastasis, we selected four cell lines (74AD, 74AD-f, 74FL, 74FL-a) from AH7974 in culture. 74AD and 74FL-a are adherent lines and 74AD-f and 74FL are floating lines. All of these cell lines strongly expressed laminin-like substances, but a marked difference was found in expression of alpha-Gal, which was most strongly expressed by 74FL, followed by 74AD, and rarely by 74AD-f and 74FL-a; the staining intensity was positively correlated with their experimental lung-colonizing potential. Cell membrane laminin-like substances were 200, 97, 62, 56 and 46 kDa and among them 62 and 56 kDa molecules were glycosylated with alpha-Gal. The pretreatment of 74FL cells with antilaminin antibody or with human type A serum (containing natural antibody to alpha-Gal epitope) depressed remarkably the lung-colonizing potential of the cells. These results suggest that the expression of 62 and 56 kDa laminin-like substances with alpha-Gal residues on tumor cell surfaces is one of the determinants associated with lung-colonizing potential of these cells. PMID- 8194196 TI - Differences in rates of incorporation of intravenously injected radiolabeled fatty acids into phospholipids of intracerebrally implanted tumor and brain in awake rats. AB - This study investigates the incorporation of three intravenously administered radiolabeled fatty acids, [9,10-3H]palmitate (3H-PAM), [1-14C]arachidonate (14C ACH) and [1-14C]docosahexaenoate (14C-DHA), into lipids of intracerebrally implanted tumor and contralateral brain cortex in awake rats. A suspension of Walker 256 carcinosarcoma cells (1 x 10(6) cells) was implanted into the right cerebral hemisphere of an 8- to 9-week-old Fischer-344 rat. Seven days later, the awake rat was infused intravenously for 5 min with 3H-PAM (6.4 mCi/kg), 14C-ACH (170 microCi/kg) or 14C-DHA (100 microCi/kg). Twenty min after the start of infusion, the rat was killed and intracranial tumor mass and brain cortex were removed for lipids analysis. Each radiolabel was incorporated more into tumor than into brain cortex. Ratios of net incorporation rate coefficients (k*) into tumor as compared with brain were 4.5, 3.4 and 1.7 for 3H-PAM, 14C-ACH and 14C DHA, respectively. Lipid radioactivity comprised more than 80% of total tumor or brain radioactivity for each probe. Phospholipids contained 58%, 89% and 68% of tumor lipid radioactivity, and 58%, 82% and 74% of brain lipid radioactivity, for 3H-PAM, 14C-ACH and 14C-DHA, respectively. Incorporation coefficients (k*i) for a phospholipid class (i)--choline phosphoglycerides (PC), inositol monophosphoglycerides (PI), ethanolamine phosphoglycerides (PE), serine phosphoglycerides (PS), and sphingomyelin (SM)--were greater in tumor than in brain for each fatty acid probe, except that values for k*PE and k*PS using 14C DHA were equivalent. Differences in k*i between tumor and brain were largest for SM and PC and the change in k*PC accounted for 65-90% of the increase in the net phospholipid incorporation rate for each probe. Differences in k*PI, k*PE and k*PS were smaller than those in were smaller than those in k*PC and k*SM, and varied with the probe. Differences in k*i were related to differences in tumor and brain phospholipid composition and metabolism. The results indicate that suitably radiolabeled fatty acids may be used to image and characterize metabolism of lipid compartments of a brain tumor in vivo using positron emission tomography. PMID- 8194197 TI - Central nervous system as sanctuary site of relapse in patients treated with chemotherapy for metastatic testicular cancer. AB - Isolated central nervous system relapse in patients treated successfully with cisplatin-based chemotherapy for testicular cancer has been described infrequently. In a retrospective analysis we identified this complication in six of 417 patients. Five of the six patients had advanced pulmonary dissemination at onset of chemotherapy, and post-chemotherapy surgery did not reveal viable tumour tissue in any of these cases. All six patients developed a single cerebral metastasis during complete remission a median four months after discontinuation of chemotherapy. Five patients were treated with surgery and subsequent radiotherapy, one patient with irradiation alone. Three patients are alive relapse-free 19, 62 and 86 months after diagnosis of cerebral relapse. One patient was alive with cerebral disease for 12 months without evidence of systemic recurrence. Our data demonstrate that the brain may act as a sanctuary site in chemotherapy-treated testicular cancer. A review of the literature shows that an isolated cerebral relapse is an extremely rare complication, but carries a relatively favourable prognosis. PMID- 8194198 TI - A murine model for bone marrow metastasis established by an i.v. injection of C 1300 neuroblastoma in A/J mice. AB - A reproducible tumor model for bone marrow metastasis has been developed by an injection of murine C-1300 neuroblastoma (C-1300 NB) cells into the tail vein of syngeneic A/J mice. The animals died with liver metastases at 18-21 days after an injection of 10(5) tumor cells and often had bone marrow metastasis in the femur. N-methylformamide (NMF), a maturational agent, was administered to inhibit liver metastases and to extend survival in mice with advancing bone metastasis. Histological examination of bone marrow metastasis, demonstrated lesions varying from a few small colonies of C-1300 NB cells either in metaphysis or diaphysis to large foci replacing normal hematopoietic bone marrow, simultaneously invading epiphysis or cortex of bone as bone metastasis. This assay demonstrated the ability to detect neuroblastoma cells in the bone marrow histologically and could determine bone marrow TD50 by extraction of bone marrow cells after treatment with various doses of drug. Fifty per cent of mice injected with cyclophosphamide (CY) developed bone marrow metastasis without liver metastasis. Treatment with tamoxifen, an anti-calmodulin drug, suppressed tumor takes in the recipient mice with tamoxifen-dose-dependent fashion. This experimental system allows for investigations into the therapeutic response and biology of neuroblastoma metastases in the bone marrow. PMID- 8194199 TI - Heterogeneities of attachment, chemotaxis, and protease production among clones with different metastatic potentials from a human pancreatic cancer cell line. AB - The present study extends our investigations into the metastatic heterogeneity among four clonal cell lines (S2-007:H, S2-013:M1, S2-020:M2, and S2-028:L) from a human pancreatic cancer cell line (SUIT-2), and extends our discussion the positive correlation between metastatic potential and the type I collagenase activity of the cells, focusing on their interaction with extracellular matrix. Ability to attach to the reconstituted basement membrane (Matrigel) was higher for clone H than clone L during an observation period of 30-60 min, whereas clones M1 and M2 were found to be intermediate in ability. In densitometric and radioactive studies, clone L exhibited the lowest collagenolytic activity against mouse and human type IV collagen, while clone H exhibited the highest activity in the densitometric study and clone M1 was the highest in the radioactive study. The production of urinary-type plasminogen activator was highest in clone L and lowest in clone H. On the other hand, tissue-type plasminogen activator was highest in clone M2 and low in both clones H and L. Clone M2 exhibited the highest chemotactic activity toward diluted Matrigel, whereas clone L had the lowest activity. On the whole, these clones showed heterogenous interactions with an extracellular matrix. It is suggested that the attachment activity to basement membrane and the type IV collagenolytic activity of the cells may be positively correlated with their metastatic potential, whereas the production of urinary type plasminogen activator was negatively correlated, but confirmation of these findings awaits further study. PMID- 8194200 TI - Different sialyltransferase activities in human colorectal carcinoma cells from surgical specimens detected by specific glycoprotein and glycolipid acceptors. AB - The amount and type of sialylation of tumor cell membranes depends on the activity of a number of different sialyltransferase enzymes. For the detection of specific activities in human colorectal carcinoma tissue several glycoprotein and glycolipid acceptors were used: desialylated fetuin, alpha 1-acid glycoprotein, beta 2-glycoprotein I, ovine submaxillaris mucin, and the gangliosides GM1, GM2, GM3 and GD1a. Because of their possible relevance for metastasis, precursors of Le(a) and Le(x) antigens, too, were employed, namely neoglycolipids produced by coupling LcOse4 or NeoLcOse4 oligosaccharides to L-alpha-phosphatidyl-ethanol amine-dipalmitoyl. Our data indicate that human colorectal tumor tissue contains two highly active sialyltransferase enzymes, which are only weakly expressed in normal mucosa. These are a N-glycan-specific alpha 2,6-sialyltransferase, which was significantly increased in metastasizing tumors, and a Gal beta 1,3Gal-NAc specific sialyltransferase, which was increased in tumors of early stages. A shift to enhanced alpha 2,6-sialylation of membrane glycoproteins during carcinogenesis was demonstrated by lectin ELISA analysis of magneto-bead separated tumor cells. Quantitative determination of specific sialyltransferase activities may be a sensitive tool for detection and monitoring of colon carcinoma. PMID- 8194202 TI - Quality improvement: then and now. PMID- 8194201 TI - An anti-invasive concentration of the alkyl-lysophospholipid ET-18-OCH3 enhances the motility of embryonal chick heart cells cultured on solid substrate. AB - Pretreatment of embryonal chick heart fragments with ET-18-OCH3 is known to induce resistance to invasion by several malignant cell lines. Embryonal chick heart fragments or cell suspensions prepared from such fragments were explanted on solid substrate and treated in medium with 10 micrograms/ml ET-18-OCH3 or with drug-free medium (control) for 48 h. This medium was washed away and replaced by drug-free fresh medium. Twenty-four to 48 h later the fast plasma membrane movements (involved in ruffling, blebbing, fast shape change and fast translocation) were quantified using a simple method based on subtracting two video images taken with an interval of 28 s. The ET-18-OCH3-treated cells showed a higher intensity of fast plasma membrane movements than control cells. Cells around a treated explant did not show the same radial alignment as in controls, suggesting loss of contact inhibition of movement. Cells from a cell suspension derived from a treated fragment showed faster translocation on solid substrate and faster shape change. We speculate that increased motility of host cells may be involved in resistance to invasion. PMID- 8194203 TI - Measuring the quality of health care. PMID- 8194204 TI - Making continual improvements to health care. AB - Health care organizations are looking for new ways to optimize the way that they provide health services. The notion that high quality health care means high costs is no longer accepted without question. Business organizations that found themselves at very high levels of inefficiency, not unlike the levels being seen in hospitals and clinics today, were able to transform their businesses by applying the principles of continual improvement. The components of knowledge for improvement, i.e., knowledge of a system, knowledge of variation, knowledge of psychology, and the theory of knowledge may seem to some too obvious to be recognized and applied on a daily basis in the workplace. Businesses and organizations that are failing, however, often lack this knowledge. We cannot be certain that management by continual improvement can or should be applied or modified to work in all health care organizations. Although the delivery of health care services is a business unlike any other, it has much in common with other service industries. The idea that the quality of patient care can be improved by using the principles of continual improvement currently is being tested. PMID- 8194205 TI - The physician-patient relationship: effects on the quality of health care. PMID- 8194206 TI - Acid-base disorders during pregnancy. PMID- 8194207 TI - Decision-making in women's health care. PMID- 8194208 TI - Technology assessment in women's health care. PMID- 8194209 TI - An outcomes-based model for directing decisions in women's health care. AB - Physicians have recognized for a long time that disease categories provide minimal information about the impact of illness on patient experiences. A diagnosis is important, because it can identify a course of treatment. However, there are considerable differences in how patients with similar diagnoses are affected. Multiple sclerosis, for example, may have essentially no impact on behavioral dysfunction or it could have devastating implications. The impact of the disease on the daily life of the patient may be more important than the diagnosis of the condition. Physicians need to learn to treat the patient, not the disease. There are only two health outcomes that are of importance. First, there is life expectancy. Second, there is function or quality of life. Biologic and physical events are mediators of these behavioral outcomes. We are concerned about cancer, high blood pressure, high cholesterol, and other problems because they may shorten a patient's life expectancy or make his or her life less desirable before death. There is a growing consensus that these behavioral outcomes are central in studies of health care and medicine. However, these outcomes, which can be obtained from standardized questionnaires, rarely are obtained in medical research and practice. A behavioral concept of health outcomes can suggest important new directions for research and practice. PMID- 8194210 TI - Decision analysis and cost-effectiveness analysis in women's health care. PMID- 8194211 TI - Improving health care through an economic approach to health care management. PMID- 8194212 TI - Carbohydrate metabolism and gestational diabetes. AB - There are significant alterations in glucose metabolism during pregnancy. In women with normal glucose tolerance, there is a significant (30%) increase in basal hepatic glucose production, a progressive (60%) decrease in insulin sensitivity, and an associated 3.0-3.5-fold increase in insulin response by 34-36 weeks' gestation. In contrast, women with normal glucose tolerance before conception who develop gestational diabetes have significant decreased insulin sensitivity relative to women in a control group. This decrease in insulin sensitivity is most apparent before conception and becomes less significant with advancing gestation. Decreased first-phase insulin response and impaired suppression of hepatic glucose production with insulin infusion develop only in late pregnancy, resulting in clinically abnormal glucose tolerance. These results are consistent with the findings of DeFronzo and Bogardus, who showed that decreased insulin sensitivity preceded the development of decreased insulin response in subjects with impaired glucose tolerance and noninsulin-dependent diabetes. Because of the relatively small number of subjects in our study population and the fact that they were not obese, our results must be interpreted with care. Additional longitudinal studies in obese subjects using comparable methods should improve our understanding of the alterations in carbohydrate metabolism in gestation in women with normal and abnormal glucose tolerance. PMID- 8194213 TI - Fluid and electrolytes in pregnancy. PMID- 8194214 TI - Diabetic ketoacidosis in pregnancy: etiology, pathophysiology, and management. PMID- 8194215 TI - Hypoglycemia in pregnancies complicated by diabetes mellitus: maternal and fetal considerations. PMID- 8194216 TI - Calcium homeostasis in pregnancy. PMID- 8194217 TI - Maternal hyperlipidemia in pregnancy. PMID- 8194218 TI - Acute endocrinopathies during pregnancy. PMID- 8194219 TI - Maternal-fetal nutrition. PMID- 8194220 TI - Massive distal femoral osteoarticular allografts after resection of bone tumors. AB - Records were reviewed for 96 patients who received distal femoral osteoarticular allografts to reconstruct femurs after wide resections of benign and malignant bone tumors. Thirteen of these were excluded from the study because of death or local recurrence. The mortality rate for all patients was 11%; for those with osteosarcomas it was 27%. The local recurrence rate was 3%. Eighty-three patients were subjected to further analysis. Their complications included fractures (14%), nonunions (12%), arthritis (10%), instability (7%), infections (6%), and resorption (6%). There was a significant difference in nonunion and infection rates between patients who received chemotherapy and those who did not. In the chemotherapy group, the infection rate was 13% versus 2% in the non-chemotherapy group. Nonunion rates were 23% versus 6% respectively. The differences in all other complication rates were not statistically significant. In patients not receiving chemotherapy (n = 53), final results were good or excellent in 70%, fair in 26%, and poor in 4%. In patients receiving chemotherapy (n = 30), final results were good or excellent in 53%, fair in 37%, and poor in 10%. PMID- 8194221 TI - Allograft reconstruction after proximal tibial resection for bone tumors. An analysis of function and outcome comparing allograft and prosthetic reconstructions. AB - Seventeen patients (age, 12-63 years; median, 22 years) treated with proximal tibial allografts were identified. Nine cases were intercalary and eight were osteoarticular allografts. Complications, number of operations, and oncologic and functional results were reviewed. The functional results of the allografts were compared with a prior cohort of patients who had endoprosthesis at the same institution by the same surgeons. There were 14 malignant tumors, two benign aggressive tumors, and one sclerosing osteomyelitis mimicking osteosarcoma. Twelve of 17 patients had complications, the most common being fracture, deformity, and infection. Six patients required more than one procedure, and three had amputations after allograft reconstruction. The ultimate function was excellent in three patients, good in seven, fair in six, and poor in one. There were 14 patients with endoprosthetic reconstruction. Wound problems followed by prosthetic loosening were the most common complications. Of the eight patients requiring a second procedure, three had an amputation. Three had excellent, seven good, and four fair functional results at the final evaluation. No patient in either group had a local recurrence. Allograft provides an alternative to endoprosthetic reconstruction; however, the high incidence of complications makes the outcome unpredictable. Allograft or prosthetic reconstruction provides better functional results than amputation without sacrificing oncologic results. PMID- 8194222 TI - Static progressive stretch to reestablish elbow range of motion. AB - Static progressive stretch (SPS) is a technique using the biomechanical principle of stress relaxation to restore range of motion (ROM) in joint contractures. Existing techniques such as dynamic splinting and traction rely on a time dependent material property, creep, which applies a continuous load. Other techniques, such as serial casting and static splinting, are time intensive and usually require assistance by a therapist. This study evaluates SPS via a new orthosis that directly applies SPS incrementally through patient-controlled therapy, allowing for stress relaxation of contracted tissue. Patients used the device in 30-minute treatment protocols. The length of treatment time varied between one and three months. Twenty patients with elbow contractures who had limited success with other treatment modalities including serial casting, dynamic splinting, physical therapy, and/or surgery, underwent SPS using the new orthosis. The increase in motion for the 20 patients in the study averaged 31 degrees (69%). All patients expressed satisfaction, with no complications and no deterioration in ROM at the one-year follow-up evaluation. PMID- 8194223 TI - Total elbow allograft for twice-failed total elbow arthroplasty. A case report. AB - A successful case of total elbow allograft after removal of a twice-failed total elbow prosthesis is reported. The patient, a disabled 63 year old at the time of allograft implantation, can now perform all activities of daily living, including household chores. Both the humeral and ulnar allografts have incorporated, and there is no evidence of degenerative changes or allograft resorption two years nine months postoperatively. PMID- 8194224 TI - Survival of the Lubinus hip prosthesis. An eight- to 12-year follow-up evaluation of 444 cases. AB - The Kaplan-Meier survival method was used to analyze 444 Lubinus arthroplasties in 398 patients who were observed between eight and 12 years. The indication for arthroplasty was osteoarthrosis in 316 hips, rheumatoid arthritis in 84 hips, and various other conditions for the other 44 hips. Survival was determined for the entire prosthesis, as well as separately for the femoral stem, the acetabulum cup, and their four subgroups. Four patient-related variables (diagnosis, gender, age, and weight) were analyzed. The overall survival of the Lubinus implants was 97.1% at five years and 87.1% at ten years. No significant difference in survival was found between the acetabular and femoral components. Survival was not significantly better with a new anatomic (SP1) stem than with the old curved one (IP). Of the four patient-related variables studied, only diagnosis and age had a significant effect on prosthesis survival. There was no difference in survival between osteoarthrosis and rheumatoid arthrosis hips, but survival was clearly poorer at ten years in the miscellaneous diagnosis group. The authors obtained a significantly lower survival percentage for patients younger than 65 years of age than for those 65 years and older. There were no deep postoperative infections in this series. The revision rate was 11.5%. The wear seen at the lower front edge of cups that were removed is discussed. PMID- 8194225 TI - Cementless total hip arthroplasty in patients with steroid-induced avascular necrosis of the hip. A 62-month follow-up study. AB - Twenty cementless porous-coated primary total hip arthroplasties (THA) were performed on 15 patients, all of whom were diagnosed with steroid-induced avascular necrosis (AVN). The average age of the patients at the time of surgery was 45 years. Minimum follow-up period for all patients was 24 months (average follow-up period: 62 months). Patients were rated using the modified Harris hip score, as well as serial radiographs. The average hip score at follow-up examination was 88, with 17 of the 20 hips having good or excellent clinical results. No revisions of the prostheses were performed. Using radiographic criteria, 12 femoral components met the criteria for bone ingrowth, seven were considered stable with fibrous fixation, and one femoral component was loose. When good initial femoral component fit was achieved, bone ingrowth reliably followed. Three acetabular components showed migration on serial radiographs. A high rate of acetabular component wear and osteolysis was noted. Avascular necrosis has been shown to adversely affect the outcome of hip arthroplasty surgery. Previous studies of patients with advanced AVN undergoing cemented THA report a high incidence of component loosening. Literature on the results of cementless THA in this patient group is sparse. The study demonstrates encouraging clinical results for cementless THA in steroid-induced AVN. Reliable femoral component fixation occurred if a good initial component fit was achieved; however, long-term acetabular loosening and wear remain serious concerns. PMID- 8194226 TI - Prognostication of nontraumatic avascular necrosis of the femoral head. Significance of location and size of the necrotic lesion. AB - After reviewing the radiographs of 149 hips with nontraumatic avascular necrosis of the femoral head (ANFH), a method for evaluating the prognosis in patients with ANFH in its early stages was devised. The evaluation was made primarily by classifying the radiographic features of each involved femoral head according to the location and size of its necrotic lesion. In a group of 120 hips, massive collapse occurred without exception in cases where both of the following criteria were true. First, in a standing position, the necrotic lesion involved more than the medial one third of the weight-bearing surface from the anteroposterior view. Second, from the lateral view, the lesion occupied more than 43% of the total area of the femoral head. However, in 29 hips, the extent and size of necrosis was less than the above, and no massive collapse occurred during the follow-up period of three to 15 years (average, 5.2 years). In these 29 hips, function was preserved. These data suggest that hips with a high risk for collapse can be reliably selected during the early stages of ANFH. PMID- 8194227 TI - Long-term results of cemented Charnley revision arthroplasty for fractured stem. AB - A prospective study of 125 cemented revisions for fractured stem, with a minimum follow-up time of one year nine months and a mean follow-up time of eight years, was performed. All arthroplasties were revised using Charnley components. At the most recent follow-up evaluation, 67.2% of patients were pain free and 22.4% had only mild or occasional discomfort. Radiographically, 107 stems (85.6%) were well fixed, six (4.8%) were definitely loose, and 12 (9.6%) were possibly loose. Thirteen hips (10.4%) required a further revision. Survivorship of the stem at the end of 11 years was 90.4%. Long-term results of cemented revision for fractured stem are very satisfactory. PMID- 8194228 TI - The perioperative management of protein S deficiency in total hip arthroplasty. AB - Protein S is an antithrombotic plasma protein that serves as a cofactor for another plasma protein, activated protein C. Patients who express a deficiency of protein S have an increased propensity to experience thromboembolic events. These events are often precipitated by factors that may cause thrombosis in nondeficient individuals, particularly in cases of trauma, pregnancy, or surgery. Anticoagulation therapy was instituted in a 45-year-old woman with known protein S deficiency and bilateral total hip arthroplasties. PMID- 8194229 TI - Lumbar decompression to treat foot drop after hip arthroplasty. AB - Twenty-one patients with spinal stenosis who developed foot drop after total hip arthroplasty were reviewed. Patients with other risk factors for nerve injury, such as dislocation, hematoma, intraoperative limb lengthening, revision surgery, and direct operative trauma, were excluded. Also excluded were patients without symptoms of spinal stenosis. Patients in this series had back and leg pain without weakness before their hip arthroplasty. When foot drop developed and persisted four months after hip arthroplasty, patients were examined with magnetic resonance imaging or myelography and computed tomography. High-grade spinal stenosis was found in each patient. Sixteen patients were treated by lumbar decompression. Twelve patients improved; six had complete recovery of foot drop. None of the five patients who did not have surgery significantly recovered. One patient developed a foot drop in the other leg after undergoing lumbar decompression. Coexisting spinal stenosis may be a risk factor for symptomatic nerve injury during hip arthroplasty. Selected patients may benefit from lumbar decompression surgery. PMID- 8194230 TI - Twin-barrelled vascularized fibular grafting to the pelvis and lower extremity. AB - From 1988 to 1992, 17 patients were treated for a large bone defect or established nonunion of the pelvis or lower extremities with twin-barrelled vascularized fibular grafts. There were 13 men and four women whose average age at operation was 39 years (range, 13-73 years). The reconstructed site was the pelvis in two patients, the femur in 12, the tibia in two, and the ankle in one. The mean length of the bone defect was 8.5 cm, and the mean length of the harvested fibula was 22 cm. Free grafts were transferred in 14 patients and pedicle grafts in three patients. The mean duration of the operation was six hours 46 minutes (range, 3.5-10.6 hours). Average blood loss was 1949 ml (range, 268-5308 ml). In one patient, the vascularized transfer failed, and recurrence of local infection was encountered in another. In the remaining 15 patients, the postoperative course was uneventful; the mean period to bony union was 5.1 months (range, two to 12 months). The mean time to full weight bearing was four months in pelvic reconstruction, 10.6 months in femoral reconstruction, and 6.3 months in leg reconstruction. Only one patient had a fracture of the fibular graft. This method is well suited for patients with a bone defect up to 13 cm in length of the pelvis or lower extremities. PMID- 8194231 TI - Cryopreservation of articular cartilage. Ultrastructural observations and long term results of experimental distal femoral transplantation. AB - Ultrastructural changes associated with the freeze-preservation of human articular cartilage have been investigated and related to changes in transplanted distal femoral allografts in nonhuman primates. Human osteoarticular specimens were frozen at 2 degrees/minute in the presence of 15% glycerol and kept in liquid nitrogen freezers (vapor phase) from one day to two years. Ultrastructural changes were confined primarily to chondrocytes and were related to the freezing phenomenon, not to the time of storage. The cartilage matrix was affected little, explaining why articular cartilage initially survives clinical transplantation, but later undergoes degenerative changes. Osteoarticular allografts of baboons were frozen in an identical fashion to the human articular cartilage and transplanted into adult baboons. Long-term observations (five years) on these animals showed healing and replacement of the osseous portion of cryopreserved allografts. Fractures that appeared to coincide with maximum revascularization of the graft were the principal complication. Articular surfaces of the cryopreserved allografts underwent degenerative changes over five years. These degenerative changes were also manifested radiologically and appeared similar to those observed in humans. By contrast, fresh osteoarticular allografts healed poorly through fibrous union. However, in one of two fresh allografts, the articular cartilage remained intact five years after transplantation. PMID- 8194232 TI - Below-knee amputee gait in stair ambulation. A comparison of stride characteristics using five different prosthetic feet. AB - The purpose of this study was to compare the stride characteristics provided by four of the new dynamic elastic response prosthetic feet and the SACH foot to determine if any of them provided an increased performance during stair ambulation. Ten traumatic below-knee amputees were studied; each of them tested all five prosthetic feet (Flex-Foot, Carbon Copy II, Seattle, Quantum, and SACH). Compression closing footswitches were used to calculate stride characteristics while ascending and descending a four-step staircase. The only significant difference between feet was found during the initial double-limb support (IDLS) phase of stair ascent, with the Flex-Foot providing a more symmetrical amputated:sound limb IDLS ratio compared with the SACH foot (1.03 versus 1.30). The increased IDLS time seen with the SACH foot reflects the inability to adequately advance the tibia and body weight over the prosthetic foot to achieve progression. This lack of progression and symmetrical gait pattern between limbs may be a function of the limited dorsiflexion range inherent with the SACH foot. PMID- 8194233 TI - Lateral tibial avulsion fractures and disruptions to the anterior cruciate ligament. A clinical study of their incidence and correlation. AB - Avulsion fractures of the lateral tibial plateau, known as the lateral capsular sign, are increasingly associated with anterior cruciate ligament (ACL) ruptures. This phenomenon, known as the Segond fracture, is a bony avulsion of the menisco tibial ligament. Stress, which can lead to an avulsion of this kind, almost always occurs during knee flexion and internal tibial rotation, and in most cases only after damage to the primary ACL stabilizer. Examination of 151 ACL ruptures revealed a Segond fracture in 9% of patients. Nearly all were caused by sports injuries and, understandably, the accident mechanism always included knee flexion and internal rotation of the tibial. In a similarly large number of other knee injuries without damage to the ACL, only one case of a Segond fracture was found. This phenomenon, which is easy to detect by radiograph, can thus be regarded as a strong indication of the presence of a ligament injury. PMID- 8194234 TI - Neglected bilateral congenital recurvatum of the knee. AB - The authors report two cases of neglected bilateral congenital recurvatum of the knee, one in a ten-year-old girl and the other in a 23-year-old man. The treatment of this rare deformity in infancy and childhood is described. A surgical approach to the deformity, which is not known to have been reported, is also presented. PMID- 8194235 TI - Comparison of functional knee braces for control of anterior tibial displacement. AB - Using a surrogate knee model, the ten custom functional knee braces that previous studies had shown to be most effective were tested for restraint to anterior tibial displacement. Testing was performed at 20 degrees knee flexion with applied forces ranging from 50 to 400 N. All braces reduced anterior tibial displacement. Resistance to anterior tibial displacement depends directly on the brace design and is inversely related to the applied force. Post-bilateral hinge shell braces exhibited the most resistance to anterior tibial displacement. Few braces were effective in controlling anterior tibial displacement comparable with a normal knee at low forces. Most of the braces were less effective at controlling anterior tibial displacement at high forces. PMID- 8194236 TI - Failure of a polyethylene total knee component presenting as a thigh mass. Report of a rare complication of total knee arthroplasty. AB - Early failure caused by wear of the polyethylene bearing surface of a metal backed tibial platform or a metal-backed patellar component in a total knee prosthesis has been a recognized complication; patients with these problems initially have pain and instability. A patient who had a cystic mass in the distal thigh was evaluated, and osteolysis of the distal femur was detected. Polyethylene debris and reactive synovium were confirmed surgically and histologically, indicating a cause-effect relationship of polyethylene wear debris and failure of the total knee arthroplasty. Regular and long-term patient follow-up evaluation after total joint arthroplasty is essential for the detection of early evidence of occult polyethylene wear. PMID- 8194237 TI - The Ilizarov technique in ankle fusion. AB - Failed ankle arthrodesis represents a significant challenge to the orthopaedist today. The complexity of this problem is further increased when associated with additional complications, such as osteomyelitis, leg length discrepancy, or concomitant foot deformity. In many instances, the only viable salvage alternative is amputation. The authors report 21 cases of complex distal tibial pathology or failed ankle arthrodesis treated with the Ilizarov external fixator. Of the 20 cases available for follow-up evaluation, 16 (80%) achieved good results with solid ankle arthrodesis and resolution of associated pathology. The Ilizarov fixator may be a viable clinical tool in these difficult cases in which amputation is the alternative. PMID- 8194238 TI - Medial subtalar dislocation associated with fracture of the posterior process of the talus. A case report. AB - A 27 year-old man was involved in a high-energy-impact motor-vehicle accident and sustained multiple injuries including a medial subtalar fracture dislocation. The dislocation of the subtalar joint was reduced by closed means, but a large, comminuted, displaced posterior process fracture remained. Open reduction and internal fixation through a posteromedial approach with mobilization of the neurovascular bundle was used to restore congruity to the subtalar joint. PMID- 8194239 TI - Intracapsular and paraarticular chondromas. AB - Intracapsular and paraarticular chondromas are rare benign tumors. The authors report four such lesions, three of which occurred about the knee and one at the hip. Radiographs showed calcified soft-tissue masses in the infrapatellar region of the knee in three patients. In the hip, the lesion was not visible on conventional radiographs. Three lesions originated from the joint capsule and one was extracapsular. These lesions should be differentiated from synovial chondromatosis and other calcified lesions occurring about the joints. After local excision, the tumors usually do not recur. PMID- 8194240 TI - Metastatic hepatocellular carcinoma to bone in a liver transplant patient. A case report. AB - Although previously unreported in the orthopaedic literature, hepatocellular carcinoma metastasizes to bone in 2 to 20% of cases. The poor prognosis associated with this tumor often results in patient demise before the need for orthopaedic intervention. A liver transplant recipient with no known history of hepatocellular carcinoma was diagnosed with this tumor when open reduction and internal fixation of an impending pathologic femoral fracture were performed. Metastatic hepatocellular carcinoma should be considered in the differential diagnosis of a lytic osseous metastasis in appropriate patient populations. PMID- 8194241 TI - Biomechanical data concerning the shoulder impingement syndrome. AB - This study evaluates forces underneath the coracoacromial vault during elevation of the arm, using a dynamic shoulder model. Muscle forces at the glenohumeral joint were simulated with hydrodynamic cylinders and applied to the deltoid muscle and to the rotator cuff through wire cables in ten anatomic specimens. Computerized regulation initiated precise, time-controlled cycles of glenohumeral joint motion. The position of the arm in all spatial orientations was measured with an ultrasonic device. Forces underneath the coracoacromial vault were recorded with capacitive sensors. The mean force during one cycle of elevation averaged 13.9 N +/- 12.5 N underneath the acromion, 0.43 N +/- 0.51 N underneath the coracoacromial ligament, and 3.44 N +/- 4.37 N underneath the coracoid process. The peak force averaged 37.8 N +/- 33.2 N underneath the acromion, 3.03 N +/- 2.62 N underneath the coracoacromial ligament, and 6.93 N +/- 7.38 N underneath the coracoid process. Forces under the coracoid process exceeded forces under the acromion in some specimens. A marked increase in forces was observed at the final stage of arm elevation and during early reverse-elevation in most specimens. The authors believe that these force values represent the pathomechanics of the shoulder impingement syndrome. PMID- 8194242 TI - Bone mineral density of lengthened rabbit tibia is enhanced by transplantation of fresh autologous bone marrow cells. An experimental study using dual X-ray absorptiometry. AB - Autologous bone marrow cells were transplanted into the primitive callus in the lengthened tibia in young and adult rabbits. Bone mineral density (BMD) in the lengthened callus was evaluated using dual-energy x-ray absorptiometry. Basal BMD in the lengthened callus in the young rabbits was higher than that in the adult rabbits (p < 0.001). Transplantation of fresh suspended bone marrow cells increased the BMD in the young (p < 0.01) and adult (p < 0.001) groups. In the young rabbits, lysate of the bone marrow cells decreased the BMD (p < 0.005). Transplantation of cultured colony-forming cells or of separated multinucleated marrow cells did not increase the BMD. The authors' study indicates that the osteogenesis of the lengthened rabbit tibia is enhanced by transplantation of fresh autologous bone marrow cells. PMID- 8194243 TI - Comparison of collagen synthesis in the peripheral and central region of the canine meniscus. AB - A comparison of collagen synthesis in the peripheral and central regions of the normal medial meniscus, the normal lateral meniscus, and the medial meniscus, three months after reconstruction of the anterior cruciate ligament (ACL), was performed in a canine model. Triangular-shaped explants were labeled in vitro with tritiated proline to compare collagen synthesis. Regional cellularity was also quantified. In the normal medial and lateral meniscus, cellularity was similar. Total collagen synthesis, as assessed by collagenase digestible material, was significantly elevated in the peripheral one-third of the medial meniscus versus the central region (paired t-test, p = 0.026). However, in the medial meniscus after ACL reconstruction, cellularity and total collagen synthesis were significantly higher in the peripheral one-third versus the contiguous central region. They were also elevated relative to the peripheral and central region of the normal medial and lateral meniscus (ANOVA, p < 0.05; Student-Neuman-Kuel test, p < 0.05). Thus, in the normal medial meniscus, the peripheral one-third may have an increased healing potential based on its increased ability to synthesize collagen. Furthermore, after ACL reconstruction, only the peripheral, and not the central, region of the canine meniscus responds to the altered mechanical and synovial environment by significantly increasing cellularity and collagen synthesis. PMID- 8194244 TI - Canine bone blood flow measurements using serial microsphere injections. AB - The objective of this study was to determine the reproducibility of serial bone blood flow (BBF) quantitation using multiple microsphere injections. Three consecutive estimates of BBF were obtained, using 15-mu radionuclide-labeled microspheres from 21 anesthetized adult dogs. A dose of 3 million spheres/kg was used in seven dogs (Cohort 1); a dose of 0.5 million spheres/kg was used in the remaining 14 dogs (Cohorts 2 and 3). Estimates of BBF were made at an average of 129, 153, and 175 minutes after the animals had been anesthetized in the first two cohorts and 179, 203, and 225 minutes in Cohort 3. The dogs in Cohort 1 had no surgical intervention; the dogs in Cohorts 2 and 3 had increasingly complex surgical interventions. Despite stabilization of cardiovascular status, BBF was found to vary by 33.4% in Cohort 1, 25.7% in Cohort 2, and 42.5% in Cohort 3 over the three injections. Cortical BBF fell by 13.9%, 12.1%, and 12.4% between the first and second, and by 31.0%, 11.2%, and 29.9% between the second and third estimates for Cohorts 1, 2, and 3, respectively. Variation in right to left blood flow was used as an overall measure of error caused by technique and did not consistently increase between the first, second, or third BBF estimates in any cohort. Cortical BBF data were found to be significantly more reliable than cancellous data (p < 0.01); error caused by technique was least in the midshaft femoral or midshaft humeral cortical samples. Increasing the dose of spheres administered from 0.5 to 3 million/kg for three serial microsphere injections increased the number of reliable samples and did not lead to increased technical error or shunting. This study demonstrates that there is a significant decrease in BBF over time in the anesthetized dog; therefore, serial estimates of BBF can only be interpreted if the results are normalized or if a control group of animals is included. PMID- 8194245 TI - The effect of experimental hemarthrosis on joint stiffness and synovial histology in a rabbit model. AB - The effect of a single injection of unpreserved blood on joint stiffness and on synovial and cartilage histomorphology in the ankle joints of rabbits was determined at ten and 28 days after injection. The same volume of saline was placed in the contralateral ankle for comparison. After ten days, the hemarthrosis ankle was stiffer than the control ankle (p < 0.027), whereas at 28 days there was no statistical difference in stiffness between the hemarthrosis and control ankles, regardless of whether the limbs had been immobilized. Also after ten days, the hemarthrosis ankles had varying amounts of clotted blood, darkened articular cartilage, hypertrophic synovium with reactive blood vessels, and macrophages containing heme. The gross and histologic appearance of the saline ankles was normal. After 28 days, there were no differences in gross or microscopic appearance between the two ankles of the caged or immobilized rabbits. All ankles exhibited retreating inflammatory response in the synovium and mild synovial thickening. Acute hemarthrosis, unassociated with fracture or discernible joint injury, caused only transient changes in joint stiffness and synovial histology. These results indicate that the presence of blood in an otherwise grossly uninjured joint should not lead to ultimate compromise in cartilage integrity or joint function. Therapeutic arthrocentesis for acute posttraumatic hemarthrosis does not appear to be necessary for the prevention of permanent problems. PMID- 8194246 TI - The diagnosis of subluxation of the hip. PMID- 8194247 TI - Oxford meniscal knee. PMID- 8194248 TI - Airport detection of modern orthopedic implant metals. PMID- 8194249 TI - Effect of plasma-sprayed calcium-phosphate coatings on bone ingrowth. PMID- 8194250 TI - Posterior sternoclavicular dislocation. PMID- 8194251 TI - Fresh osteochondral allografts for treatment of articular defects in osteochondritis dissecans of the lateral femoral condyle in adults. AB - Fresh osteochondral allografts were used to patch defects in the lateral femoral condyle in 17 patients with osteochondritis dissecans. The patients included 12 males and five females, ages 16 to 46 years. All had previously undergone other procedures including pinning (4), primary removal of osteochondral fragments (16), and abrasion arthroplasty (14). Defects up to 3 cm in diameter were treated with isotopic grafts and fixed with Herbert screws. Larger defects were treated with crescent-shaped grafts fixed with multiple Herbert screws. Follow-up time ranged from two to nine years. Pain, stiffness, swelling, buckling, and locking were ablated in 16 of the 17 patients. No graft collapse has been noted in these individuals. Verification of graft viability was achieved at periods from six weeks to six years, typically at the time of hardware removal. The only failure occurred in an individual with a 3- x 4.5-cm defect who suffered gross fragmentation which left a large crater. Osteochondritis dissecans of the lateral femoral condyle provides an ideal opportunity for evaluating osteochondral grafts. Sixteen of 17 grafts were a success at two to nine years after surgery. PMID- 8194252 TI - Osteoarticular allografts to treat distal femoral osteonecrosis. AB - Allografts, which are among the limited number of treatment options for young patients with large defects of the distal femur, offer a physiologic method of restoring knee function. Since 1980, 21 patients younger than 50 years old who had osteonecrosis involving large portions of the distal femur were treated with fresh-frozen osteoarticular surface replacements. This retrospective review evaluated the 15 patients (17 knees) whose follow-up time was greater than two years. The patients were reevaluated at regular intervals by one or more of the authors. Follow-up time ranged from two to nine years (mean, 4.2 years). Outcome was classified as either excellent, good (occasional complaints, unlimited walking without aids, functional range of motion), fair (intermittent pain, ambulatory tolerance limited), or failure. There were seven excellent results, five good results, one fair result, and four failures. There were no infections, nonunions, or wound complications. At this early follow-up period, 12 (70%) of the 17 knees have been successfully treated. The authors' success rate with frozen allografts is comparable to the results of fresh allograft resurfacing. Use of frozen allografts allows time for thorough testing for viral and bacterial infections, is more practical, and the allografts are available for use in elective surgery. Failure in this series was principally the result of degeneration of the allograft's articular cartilage, or fracture of the allograft. PMID- 8194253 TI - Treatment of elbow ankylosis by means of transplantation of the entire joint. Preliminary communication. 1908. PMID- 8194254 TI - Current status of allograft meniscal transplantation. AB - The meniscus has several roles that contribute to knee function. Many clinical studies have documented the detrimental effects of loss of meniscus function. Meniscal repair is recommended when technically and anatomically feasible to preserve meniscal function. Techniques for meniscal repair can be used to transplant meniscal allografts. Animal studies have documented that meniscal allografts can heal in the recipient. There are few clinical studies of meniscal allograft transplantation in humans. Indications, techniques, results, and complications of meniscal allograft transplantation in humans are described. PMID- 8194255 TI - Freeze-dried fascia lata allografts in the reconstruction of anterior cruciate ligament defects. A two- to seven-year follow-up study. AB - A study of 70 arthroscopic anterior cruciate ligament reconstructions with nonaugmented human freeze-dried fascia lata grafts is reported. The overall results are based on subjective, objective, and radiologic examinations as well as second-look arthroscopies at the one-year, four-year, and five-year follow-up evaluations. The average follow-up time was 4.5 years (range, two to seven years). Mention is made of pertinent points from patient histories, and an account is given of associated lesions that had been previously operated on or which were treated concomitantly. The subjective results show 82% excellent and good results, and the objective results show 95% excellent and good results. This difference may be explained by the subjective residual pain reported by every patient who suffered a work compensation injury; residual pain was not reported very often by those whose injuries were sports related. Forty-seven patients underwent second-look arthroscopies at one year, and seven underwent arthroscopy at four and five years after operation. These examinations provided very interesting clues as to the graft's future status. It was possible to identify zones of neovascularization, tissue invasion, and unraveling of the graft as well as to test for stability with a probe. Biopsies and histologic studies confirmed superficial and deep ligament revascularization as early as four months after operation. Results of arthroscopy at one year confirmed the results of physical examination and the prognosis for the graft. PMID- 8194256 TI - Reconstruction of anterior cruciate ligaments with bone-patellar tendon-bone and achilles tendon allografts. AB - Two hundred fourteen patients had anterior cruciate ligament (ACL) reconstructions performed with banked freeze-dried or frozen allografts using an arthroscopic-assisted technique. Of these, 181 patients were available for follow up testing and examination. Minimum follow-up time was four years (average, 57 months). All patients were evaluated by using KT-1000 arthrometer and Biodex testing as well as by physical examination. Final results were rated as satisfactory or unsatisfactory by using a modified Feagin knee scoring scale. Patients who were classified as good or excellent were considered to have satisfactory results. Those who were classified as fair or poor were considered to have unsatisfactory results. During the course of the study, 79% of the patients had satisfactory results. The percentage of patients with satisfactory results increased as the study progressed. The surgical technique was modified as new biomechanical principles were applied to ACL reconstruction. Rehabilitation of the patients was also progressively changed from conservative to aggressive. The authors attribute the improvement from 67% of patients with satisfactory results in 1984 to 85% in 1988 at least partially to these modifications. It was concluded that either frozen or freeze-dried aseptically excised and processed bone-patellar tendon-bone and Achilles tendon allografts can serve adequately for the reconstruction of ACLs. Complications may be reduced and clinical end results improved by adherence to an exact, reproducible surgical technique and an aggressive rehabilitation regimen. PMID- 8194257 TI - Extensor mechanism reconstruction with an allograft after total knee arthroplasty. AB - The authors report on a series of 15 knees in which an extensor mechanism allograft was used to treat a rupture of the patellar tendon associated with a total knee arthroplasty. Nine of the knees have greater than two-year follow-up evaluation (average, 4.1 years; range, 2.3-7 years). Postoperatively, the average flexion was 106 degrees. All but three patients achieved full passive extension. Six of the nine knees had no extensor lag. The average post-operative clinical score for the follow-up group was 78 points. Graft complications include one early graft rupture, one early quadriceps junction failure, and one patellar component loosening. One graft fractured after revision of a metal-backed patella. PMID- 8194258 TI - Human bone and tissue allografts. Preparation and safety. AB - Currently, modern tissue banks routinely supply requested bone and soft-tissue allografts. These allografts are safe if tissue-bank personnel adhere to the existing methodology for excluding any donors with potential for disease transmission. The authors' discard rate after excision of tissues has been approximately 18%, reflecting their concern for allograft safety. The preparation of significant numbers of allografts is labor intensive and very expensive, as is multiphasic screening of donors. However, long-term success with a large number of bone or soft-tissue recipient patients has led physicians and patients to have confidence in the safety of allografts prepared as described. PMID- 8194259 TI - Technique and results of allograft reconstruction in revision total knee arthroplasty. AB - This study reports more than four years of experience with bone allografts used to reconstruct large uncontained defects in the femur and the tibia in patients requiring revision total knee arthroplasty. Nineteen allografts were used, 13 in the distal femur and six in the proximal tibia. The average follow-up period was 2.1 years. After these complex revision arthroplasties, the average knee score improved from 29 to 87 points. The average patient function score increased from 35 to 85 points. Bulk allografts are effective in the reconstruction of uncontained defects in revision total knee arthroplasty. PMID- 8194260 TI - Replacement of the distal femur and proximal tibia with frozen allografts. AB - Eighty-eight osteoarticular distal femoral allografts and 68 proximal tibial allografts have been transplanted at the authors' institution from 1958 to 1970. These allografts were used in limb-sparing operations performed after the diagnosis of benign or malignant tumors. All allografts were preserved by freezing to -70 degrees or -30 degrees. Allograft fixation technique depended either on press fitting of the allograft host junction or on quadrangular titanium intramedullary rods. The most prevalent long-term complication was the time-dependent development of destructive arthrosis. After excluding patients with tumor failures (8.3%) and those with failures caused by infections, amputations, or allograft removal without subsequent replacement (5%), 135 patients remained. In this group of patients, after treatment of complications, good or excellent results were obtained in 31% of patients, and fair results in 45% of patients. In the latter group, significant limitation of knee motion existed. The remainder (24%) had either complete limitation of knee motion or had to rely on orthopaedic bracing. PMID- 8194261 TI - [Relationship between thermal threshold and population of peripheral nerve fibers]. AB - The relationship skin thermal threshold (TT) and density of both myelinated and unmyelinated fibers were investigated in 12 patients with various peripheral nerve diseases including Crow-Fukase syndrome, carcinomatous neuropathy and Charcot-Marie-Tooth disease. The TT was measured at a site above the medial tibial condyle using a thermal threshold tester. The TT was defined as the threshold at which a slight rise or fall in temperature could be detected. The size of the skin stimulation area was 13.5 cm2, the temperature change rate was 1 degrees C/sec, and the basal temperature was set at 34 degrees C. A sural nerve biopsy was performed and an image processor (IBAS) was used to measure the nerve fiber density. The TT in the patients with peripheral nerve disease was found to be elevated when compared with that of the 74 healthy controls (mean age of 38.1 +/- 13.3 years). Elevation of the TT has an intimate relation to damage of the small myelinated nerve fibers. In conclusion, unmyelinated fibers may play a relatively minor role in conveying thermal sensation. PMID- 8194262 TI - [Antihypertensive drugs in acute stage of atherothrombotic infarction deteriorate the outcome]. AB - To elucidate whether high blood pressure in acute brain infarction should be treated or not, we retrospectively investigated relationship of the use of antihypertensive agents in the acute stage with the area of hypodensity on CT examined one month after onset and functional outcome at discharge. Actual blood pressure value and diurnal fluctuation in the acute stage were also related to the infarct size and outcome. Subjects were compared of 32 atherothrombotic stroke patients with unilateral severe stenotic lesion (> or = 75% stenosis or occlusion) at the extracranial carotid artery or the horizontal portion of the middle cerebral artery confirmed by cerebral angiography. Seven patients (treated group) received antihypertensive drugs within 14 days of onset and the remaining 25 patients (non-treated group) did not. The data of frequent blood pressure measurements were available in five of the treated group and 24 of the non treated group. There were no significant differences in the daily highest and lowest mean arterial blood pressure (MABP) between the two groups (124.8 +/- 11.8 mmHg vs. 118.5 +/- 13.5 mmHg and 101.9 +/- 10.4 mmHg vs. 104.4 +/- 12.6 mmHg, respectively). However, apparent circadian fluctuation of the MABP (the highest MABP--the lowest MABP > 25 mmHg) was more frequently seen in the treated group (3/5, 60%) than in the non-treated group (0/24, 0%) (chi 2 test, p < 0.01). Large infarcts (> or = 10 cm2) were more commonly found in the treated group (4/7, 57%) than in the non-treated group (1/25, 4%) (chi 2 test, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194263 TI - [Correlation between degrees of the CTG repeat expansion and clinical features of myotonic dystrophy]. AB - The mutation in myotonic dystrophy gene has recently been identified as an unstable expansion of trinucleotide CTG repeat located at the 3'-untranslated region of myotonin protein kinase gene. In this paper we report the correlation between the degree of CTG amplification and clinical features in 35 individuals with myotonic dystrophy. The analysis of CTG repeat expansion was performed with Southern blot hybridization. Genomic DNA from peripheral blood leukocytes was digested with a restriction endonuclease, Pst I, instead of commonly used EcoRI. Since small expansion (about 100 bp) could be detected with PstI digestion and furthermore, the DNA fragment did not contain insertion/deletion polymorphism, we were able to accurately determine the exact sizes of CTG repeat expansion. We have observed a tendency of earlier ages of onset with larger allele sizes. The good correlation between the size of the expansion and the severity in muscle weakness was clearly demonstrated especially if the analysis was focused on the patients at same age group at 40-45 years. The severity of motor disability was classified into three stages. The mean size of expansion was 0.33 +/- 0.17 (M +/- SD) kbp in stage I, 2.58 +/- 1.42 kbp in stage II, and 4.75 +/- 0.93 kbp in stage III. The tendency was also observed when patients were categorized according to the intellectual grade. The anticipation was observed in all the parent-child pairs. When the increases of the repeat expansions were compared between father child and mother-child transmissions, broader variation of the increases was observed in father-child transmissions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194264 TI - [Common carotid artery thrombosis--clinical and radiological evaluation]. AB - Common carotid artery thrombosis (CCAT) is not common. We studied 4 patients with CCAT to clarify the clinical and radiological features of this disorder. Case 1 had only episodes of TIA. Case 2 was diagnosed by chance as having CCAT at the time of admission due to cerebellar infarction. On the contrary, Cases 3 and 4 were admitted because of disturbance of consciousness and hemiparesis. Case 4 died soon after his stroke because of complications. We evaluated cases 1, 2 and 3 using head CT, head MRI, neck MRI, MR angiography, SPECT and cerebral angiography. Case 4, who was evaluated with head CT and cerebral angiography, was autopsied to confirm the occlusion of the common carotid artery. The clinical severity of CCAT varies from asymptomatic to severe, because each differs in the time taken for complete occlusion of the common carotid artery; the development of collateral circulation; and hemodynamics of the brain. As for the collaterals their contribution is variable; for example, the thyrocervical and other arteries function as the bypass. We can diagnose CCAT easily and noninvasively using MR angiography and neck MRI based on disappearance of the flow void in the common carotid artery or internal carotid artery. On physical examination, it is important to detect faded pulsation of the superficial temporal artery that is ipsilateral to the occluded common carotid artery. PMID- 8194265 TI - [Clinical feature and mechanism of cardiac failure in patients with Becker muscular dystrophy]. AB - Patients with Becker muscular dystrophy (BMD) have milder muscular impairment and better prognosis than patients with Duchenne muscular dystrophy (DMD). Another difference is that while cardiac failure due to myocardial involvement is a frequent cause of death in BMD, respiratory failure is the most common cause of death in DMD. We examined cardiac function and the mechanism of cardiac failure in 21 BMD patients aged 3 to 63 years (mean, 40.4) by electrocardiography, mechanocardiography, echocardiography, and post-mortem examination. Diagnosis of BMD was made by characteristic symptoms, dystrophic change in muscle histology, and the followings: 1) a deletion in the dystrophin gene, 2) "patchy" staining of dystrophin on immunocytochemical analysis, 3) abnormal dystrophin size on Western blotting, and 4) presence of a definite carrier in the family. To be diagnosed as BMD, patients exhibited one or more of 1)-3). Patients who were diagnosed only by 4) had a relative who had been diagnosed as BMD by one of 1)-3). The control group included 43 DMD patients (age 4-26 years, mean 16.2) and 20 healthy males (age 15-60 years, mean 33.3). Electrocardiogram showed prominent Q waves in leads II, III, aVF and V6, and tall R in V1, suggesting myocardial injury in the posteroinferior and lateral walls. The ratio of ejection time to pre-ejection period (ET/PEP) decreased to 2.0-3.3 in BMD, and was significantly lower than that in DMD patients with comparable muscle weakness. Left ventricular dilatation became more prominent with age, and end-diastolic left ventricular dimension (EDLVD) averaged 52.3 mm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194266 TI - [Dystrophin-related protein in diaphragm, limb and myoblast transferred muscles of mdx mouse]. AB - Expression of the dystrophin-related protein (DRP or Utrophin) was examined with Western blot and immunohistochemical methods in diaphragm, limb and also in myoblast transferred muscles of the mdx mouse. Although we have hypothesized that progressive fibrosis in the diaphragm of the mdx mouse has been due to a smaller amount of DRP expression compared with limb muscles, we could not find any difference in the amount of DRP or in the DRP localization pattern between the two muscle sites. In limb muscles treated with myoblast transfer, dystrophin positive muscle fibers had no DRP on their surface membrane, although dystrophin negative muscle fibers were DRP-positive. These findings suggest that excessive expression of DRP is suppressed in the normalized muscle fiber with dystrophin. It also appears that the histological differences seen in the different muscles of the mdx mouse are not due to the amount of DRP present. PMID- 8194268 TI - [Three siblings of painful muscle cramps (generalized muscle cramp disease) with alopecia and endocrinological disorders]. AB - Three siblings with generalized painful muscle cramps, generalized alopecia, and endocrinological abnormalities are presented. Their clinical features are very similar to those in sporadic cases reported as having generalized muscle cramp disease. Autosomal recessive inheritance was suggested in our patients. Abnormal laboratory tests include hypersecretion of insulin after glucose loading, elevated levels of luteinizing hormone (LH) and follicular stimulating hormone (FSH), and hypersecretion of LH in the LH-RH test. An elevation of IgG and IgG index in the cerebrospinal fluid (CSF) of two patients suggests IgG production in the CSF. Oral administration of 75 to 150 mg of dantrolene sodium decreased the frequency, intensity, and duration of cramps in all cases. Autoimmune mechanisms based upon hereditary abnormalities are suggested as a cause of their disease. PMID- 8194267 TI - [Probable Bickerstaff's brainstem encephalitis associated with anti-GQ1b antibody]. AB - We presented a case of probable Bickerstaff's brainstem encephalitis. A 39-year old woman developed easy falling, progressive consciousness disturbance, total ophthalmoplegia, and bilateral pyramida tract sign. In serum anti-ganglioside antibody assay using enzyme-linked immunosorbent assay, high anti-GQ1b antibody was found. Electroencephalography was dominated by alpha activity, superimposed with occasional theta wave bursts. Brain MRI showed abnormal signal hyperintensities in the tegmentum of the midbrain to the upper pons on T2 weighted images and swelling of the midbrain and pons on T1 weighted images. Five days after the onset of the disease, she had respiratory arrest, which necessitated artificial ventilation for a few days. Then, she began to recover. However, she gained only partial recovery, leaving upward gaze palsy, right abducens nerve palsy, pseudbulbar palsy and quadriplegia. PMID- 8194269 TI - [Myopathy, cerebellar ataxia and Williams syndrome like features in siblings]. AB - Two female cases, 23- and 21-year-old, of supravalvular aortic stenosis associated with cerebellar hypoplasia, retinitis pigmentosa and myopathy were reported. No family history of mental retardation and cardiovascular anomalies was found. There was no consanguinity between the parents. Pregnancy, labor and delivery were reported to be uncomplicated. When they visited to our hospital at the age of 13 and 11 years, they had short stature, characteristic facial appearance (eg, wide mouth, elongated philtrum, low nasal bridge and broad forehead) and supravalvular aortic stenosis. Neurological examination disclosed mental retardation, retinitis pigmentosa, muscle wasting and contracture of bilateral knee and ankle joints. Gait was unsteady and bradykinetic. Their smooth pursuiting ocular movements were saccadic. No nystagmus was recorded. Mild intention tremor was present. The muscles were slightly hypotonic, but deep tendon reflexes were hyperactive in the lower extremities. The sensory system was normal. Results of chromosome analysis and urine amino acid analysis were normal. The serum creatine kinase was elevated to 1,000-3,000 U. Muscle biopsy revealed nonspecific myopathic changes such as variability of fiber diameter in both fiber types. Neither cell infiltration nor deposits of fat or glycogen was found. Cranial MRIs performed at the age of 22 and 20 years disclosed cerebellar hypoplasia and moderate enlargement of the fourth ventricle. The two cases resembled clinically those of Williams syndrome, but the MRI findings were not consistent with those of the syndrome. The disorder is considered to be either Williams syndrome complicated by some other relatively rare clinical features, or another heredofamilial disease partly resembling Williams syndrome. PMID- 8194270 TI - [Ataxic hemiparesis with ipsilateral cheiro-oral syndrome due to a single lacunar infarct at the border between the posterior limb of the internal capsule and the corona radiata]. AB - A patient with ataxic hemiparesis and ipsilateral cheiro-oral dysesthesia (tingling) due to a single lacunar infarct at the border between the posterior limb of the internal capsule and the corona radiata is described. A 47-year-old hypertensive man was admitted because of weakness of the right upper and lower limbs with ipsilateral peri-oral and palmar dysesthesia, which developed during bathing in the morning. Upon admission, neurological examination revealed right hemiparesis with ipsilateral limb ataxia and ipsilateral peri-oral and palmar dysesthesia. Based on neurological finding, he was diagnosed as having ataxic hemiparesis with ipsilateral cheiro-oral syndrome. Brain computed tomography and magnetic resonance imaging demonstrated a small lesion at the border between the posterior limb of the left internal capsule and the corona radiata, which was enhanced with gadolinium-DTPA administration. It has been reported that the disturbance of the cortico-pontine tract causes ataxic hemiparesis and that of the thalamo-cortical projection causes cheiro-oral syndrome. These findings of the present case, therefore, suggest that both of these pathways run closely together at the border between the posterior limb of the internal capsule and the corona radiata. PMID- 8194271 TI - [Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes with delayed and decreased cerebral blood flow on cerebral angiography- a case report]. AB - A 9-year-old girl was admitted to our hospital because of fever, headache, vomiting, and convulsive seizures. On admission, she was proved to have homonymous hemianopsia as well as elevated lactate and pyruvate levels in both serum and cerebrospinal fluid. Muscle biopsy study showed scattered ragged-red fibers and strongly succinatedehydrogenase-reactive blood vessels (SSV), suggesting systemic vascular involvement. She had a point mutation at nucleotide pair 3,243 in mitochondrial DNA extracted from muscle and blood samples. Brain CT and MRI showed a large abnormal area mimicking cerebral infarction in the region of the occipital cerebral artery. The cerebral lesion was assumed to be caused by vascular abnormality because of delayed and decreased cerebral blood flow together with vascular changes in her muscle biopsy. PMID- 8194272 TI - [Rapid diagnosis and therapeutic evaluation of herpes simplex encephalitis using polymerase chain reaction from cerebrospinal fluids]. AB - We made a diagnosis and therapeutic evaluation of herpes simplex encephalitis using polymerase chain reaction (PCR). Cerebrospinal fluids (CSF) of 24 patients suspected of meningoencephalitis were examined by PCR. HSV (herpes simplex virus) DNA was demonstrated in 3 patients, in which CSF anti-HSV antibody raised, and moreover in another patient, lacking the raise of the HSV antibody. Since this patient was considered to suffer from HSV encephalitis by clinical symptoms and findings on brain CT, this result suggests authenticity of the PCR for detection of HSV infection. HSV-DNA in the 4 patients were semi-quantitated. The amount of the DNA reduced and disappeared corresponding to their improvement of clinical symptoms and laboratory data. Thus, the present method is considered to be useful for rapid diagnosis of HSV encephalitis, and also for evaluation of effects of therapy to decide whether administration of anti-herpes drugs should be stopped. PMID- 8194273 TI - [A case of cervical spondylitis mimicking motor neuron disease]. AB - The patient was a 65-year-old man who had noted mild weakness of the right hand since summer, 1990. In October, 1990, he had fever and developed apparent weakness of the upper extremities. Neurological examination on admission revealed distal dominant muscle weakness and atrophy of the upper extremities with fasciculation. Deep tendon reflexes were diminished in the upper limbs and exaggerated in the lower ones. No sensory disturbance or cerebellar signs were recognized. Laboratory examination of his blood showed leukocytosis and elevated levels of acute reactants. The needle EMG showed a neurogenic pattern. MRI study of the neck disclosed narrowing of the intervertebral space between C7 and Th1 and a low signal intensity of these vertebral bodies on T1 weighted image. Treatment with antibiotics improved his neurological symptoms and the abnormal MRI findings. The present case was diagnosed as having cervical spondylitis. Neurological symptoms and signs associated with cervical spondylitis have been reported to be paraplegia or quadriplegia. Like the present case, however, cervical spondylitis should also be considered as one of the diseases which could show symptoms and signs very similar to those of motor neuron disease. PMID- 8194274 TI - [A case of acute cholinergic dysautonomia]. AB - A 52-year-old man with hypohidrosis and selective parasympathetic peripheral autonomic nerve disturbances of acute onset is described. In April 1991, he noted a feeling of dryness in the eyes and the oral cavity, disturbance of taste, difficulty in micturition and a feeling of dryness at the distal extremities with acute onset, which were followed by alternating diarrhea and constipation. Clinical and laboratory autonomic examinations revealed decreased sweating in the distal extremities, decreased lacrimation and salivation, a decrease in the average urinary flow with residual urine and hypersensitive pupillary constriction to the instillation of methacholine. On the other hand, the results of upright tilt testing, the Valsalva test and cold pressor test were all normal, and the plasma noradrenaline level was also normal. Therefore, the diagnosis of acute cholinergic dysautonomia was made. He resumed his clerical work without medication 3 months after the onset. One year and 4 months after the onset, clinical and laboratory examinations showed that hypohidrosis in the distal lower extremities remained unchanged. We found ten patients of acute cholinergic dysautonomia in the literature, and concluded that our patient should be classified as a typical case of this disease. Clinical reports of acute cholinergic dysautonomia are relatively rare, and our patient is the oldest among the reported patients. PMID- 8194275 TI - [A case of cerebral pedunclar infarction presenting with pure motor hemiparesis]. AB - Left pure motor hemiparesis occurred in a 42-year-old woman with a history of hypertension and diabetes mellitus. The left hemiparesis affected the arm and leg equally. The face was almost spared, with only a very slight facial asymmetry. Brain CT and MRI showed a small infarction located in the external 2/3 of the right cerebral peduncle. Cerebral angiography did not reveal significant abnormalities. PMID- 8194276 TI - [A case of Weber's syndrome due to gradual expansion of a basilar bifurcation aneurysm]. AB - We report an 82-year-old female who developed Weber's syndrome following gradual expansion of a basilar bifurcation aneurysm. The patient first developed subarachnoid hemorrhage at the age of 78. Cerebral angiography showed an intracranial aneurysm of 1 cm diameter at the bifurcation of the basilar artery. Three years later, the patient was readmitted because both CT and MRI at that time revealed that the lumen of the aneurysm was filled with an organizing thrombus. On her third admission at the age of 82, the diameter of the aneurysm was expanded to 2.5 cm and Weber's syndrome had developed. On T2-weighted MRI, a central low-intensity area surrounded by a high-intensity zone were evident in the aneurysm, suggesting the formation of an organized or organizing thrombus. Repeated MRI examinations are useful for following the expansion of a thrombosed aneurysm. PMID- 8194277 TI - [Bacterial cerebritis developed from purulent meningitis--serial CT and MRI study of a case]. AB - A 54-year-old woman was admitted to our hospital because of purulent meningitis caused by Streptococcus pneumoniae during a long-term administration of prednisolone for the treatment of bronchial asthma. After admission, both antibiotics and steroids were given, which resulted in her good general and neurological condition, and the normal protein and glucose content in her cerebrospinal fluid three weeks later. However, post-contrast computerized tomography (CT) at this time showed various size of multiple irregular high densities devoid of capsular component in the white matter of the bilateral cerebral hemisphere. MRI examination revealed that the lesions were of low intensity on the T1-weighted sequence whereas high on T2-weighted sequence. Gd DTPA enhanced the T1-weighted images on these lesions. These findings may indicate that the lesions were at the pre-encapsulation stage of cerebritis, because the lesions were gradually reduced and disappeared after the subsequent antibiotic therapy. It is emphasized that patients with purulent meningitis under steroid therapy require careful observation for the risk of bacterial cerebritis. PMID- 8194278 TI - [Familial cases presenting spastic paraparesis, mental disturbance and thinning of corpus callosum]. PMID- 8194279 TI - [Three siblings homozygous for the transthyretin-Met30 gene in familial amyloidotic polyneuropathy--evaluation of their clinical pictures with reference to those of other 10 cases reported]. AB - We reported clinical pictures of three siblings homozygous for a transthyretin Met30 (TTR-Met30) gene in a family with familial amyloidotic polyneuropathy (FAP) type I residing in Kanazawa city, and evaluated their clinical pictures with reference to those of other 10 cases previously reported. Ages at onset of two homozygous patients with FAP were 58 and 68 years. They showed sensory-dominant polyneuropathy and mild autonomic dysfunctions. One of them showed vitreous opacities and the other showed multifocal white sheaths along the retinal blood vessels and obstruction of the vessels. A morphometric study of the sural nerve in one patient showed a marked reduction in both myelinated and unmyelinated nerve fiber densities. The third subject was an asymptomatic carrier aged 59 years. The studies of our cases and those in the literature have shown the clinical features of homozygotes for the TTR-Met30 gene as follows: (1) all the homozygous subjects belong to families with incomplete penetrance of the disorder; (2) the clinical features common to 10 symptomatic homozygotes are late onset, mild autonomic dysfunctions, and high frequency of ocular amyloidosis; (3) there are three asymptomatic cases. In addition to TTR-Met30 abnormality, some unknown mechanisms that control its deposition into the tissues are presumed to be involved for the onset of FAP. PMID- 8194280 TI - Pharmacokinetic considerations in rational drug design. PMID- 8194281 TI - Ceftibuten pharmacokinetics and pharmacodynamics. Focus on paediatric use. AB - Ceftibuten is an extended-spectrum, cephem antimicrobial agent formulated for oral administration. Ceftibuten is absorbed by carrier-mediated processes and passive diffusion. The absorption of ceftibuten is described adequately by a first-order process. Following oral administration, peak serum ceftibuten concentrations are reached within 2 to 3 hours. Although the absolute bioavailability of ceftibuten in humans is not known, its relative bioavailability indicates that there is relatively rapid and complete absorption of the drug. Administration of ceftibuten with food may decrease the rate of absorption and, in the case of high fat meals, may decrease the extent of absorption by approximately 20 to 30%. The results of limited studies indicate that the drug distributes well into various body tissues and fluids, with relatively high concentrations being achieved in organs that receive a significant portion of the cardiac output. In adults with normal renal function or chronic renal failure, the apparent volume of distribution (Vd/F) for ceftibuten ranges from 0.2 to 0.4 L/kg and the total plasma clearance (CL/F) ranges from approximately 61 to 75 ml/min (3.7 to 4.5 L/h). Studies of ceftibuten elimination in adults have demonstrated positive linear correlation between CL/F and creatinine clearance. Following administration of a single dose of ceftibuten, approximately 67 to 94% of the drug has been recovered in the urine unchanged. The elimination half-life (t1/2 beta) of ceftibuten in adults with normal renal function is approximately 2.5 hours. Significant accumulation of ceftibuten does not occur with repeated administration. Despite the fact that the mean time taken to achieve maximal serum concentration (tmax) [1.1 to 2 hours] and t1/2 beta (2.1 hours) following administration of a single dose of ceftibuten to infants and children were similar to values previously reported in adults, the Vd/F (0.42 L/kg) and CL/F (3.1 ml/h/kg) were considerably greater in children younger than 5 years. Additionally, the apparent nonrenal clearance of ceftibuten in paediatric patients (52% of CL/F) was greater than reported for adults (approximately 32% of CL/F) with normal renal function. Thus, developmental differences appear to affect the pharmacokinetic profile of ceftibuten. Ceftibuten has a wide spectrum of antimicrobial activity against both Gram positive and Gram-negative pathogens, and is stable to hydrolysis by a large number of beta-lactamases. Notable exceptions with regard to the Gram-positive spectrum for ceftibuten include relative or documented resistance for most strains of Listeria, Staphylococcus aureus, S. epidermidis, penicillin-resistant strains of Streptococcus pneumonia and S. enterococcus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8194282 TI - Clinical pharmacokinetics and pharmacology of trimetrexate. AB - Trimetrexate represents one of a number of new antimetabolites that have been studied in malignant, rheumatological and infectious disease. Methotrexate, the classical antifolate agent, is active in a broad spectrum of clinical settings, but its use is limited ny pre-existing or acquired cellular resistance. Trimetrexate is an agent that does not require uptake by the folate carrier transport system, a major mechanism of cellular resistance both in vitro and in vivo. Both dihydrofolate reductase inhibition and high performance liquid chromatography (HPLC) assays can be used to determine drug concentrations. Clearance of trimetrexate has been reported to follow biphasic or triphasic patterns. Elimination is primarily by biotransformation with less than 5% of the drug excreted renally in an unchanged form. Both active and inactive metabolites have been found, but the precise metabolic pathways have yet to be defined. The role of trimetrexate in the treatment of Pneumocystis carinii pneumonia is limited to compassionate use, as clinical studies have shown cotrimoxazole (trimethoprim-sulfamethoxazole) to be superior to trimetrexate. However, in a wide spectrum of malignant processes, trimetrexate appears to have a role either as a high-dose single agent, with calcium folinate (leucovorin calcium) rescue, or in combination with other antineoplastic agents. However, further trials are needed to fully establish the efficacy of trimetrexate in these settings. Increased knowledge of the pattern of resistance for individual tumours and tumour types may result in trimetrexate becoming more widely used clinically. PMID- 8194283 TI - Clinical pharmacokinetics of fluoxetine. AB - Fluoxetine is well absorbed after oral intake, is highly protein bound, and has a large volume of distribution. The elimination half-life of fluoxetine is about 1 to 4 days, while that of its metabolite norfluoxetine ranges from 7 to 15 days. Fluoxetine has a nonlinear pharmacokinetic profile. Therefore, the drug should be used with caution in patients with a reduced metabolic capability (i.e. hepatic dysfunction). In contrast with its effect on the pharmacokinetics of other antidepressants, age does not affect fluoxetine pharmacokinetics. This finding together with the better tolerability profile of fluoxetine (compared with tricyclic antidepressants) makes this drug particularly suitable for use in elderly patients with depression. Furthermore, the pharmacokinetics of fluoxetine are not affected by either obesity or renal impairment. On the basis of results of plasma concentration-clinical response relationship studies, there appears to be a therapeutic window for fluoxetine. Concentrations of fluoxetine plus norfluoxetine above 500 micrograms/L appear to be associated with a poorer clinical response than lower concentrations. Fluoxetine interacts with some other drugs. Concomitant administration of fluoxetine increased the blood concentrations of antipsychotics or antidepressants. The interactions between fluoxetine and lithium, tryptophan and monoamine oxidase inhibitors, in particular, are potentially serious, and can lead to the 'serotonergic syndrome'. This is because of synergistic pharmacodynamic effects and the influence of fluoxetine on the bioavailability of these compounds. PMID- 8194285 TI - Pharmacokinetic optimisation of the treatment of osteoarthritis. AB - Osteoarthritis is the most frequently encountered form of arthritis worldwide. Pharmacological therapies consisting of nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics such as paracetamol (acetaminophen), codeine and dextropropoxyphene are the principal means of symptom control. Osteoarthritis appears to have little impact on the pharmacokinetics of these drugs per se. However, other clinical features commonly associated with patients with osteoarthritis, such as advanced age, obesity or concurrent diseases and medications, may be important. A limited number of concentration-response studies have demonstrated the existence of a pharmacokinetic/pharmacodynamic relationship for these drugs. However, the information derived from patients with osteoarthritis is very limited. Simple analgesics have been shown to be as effective as NSAIDs in some studies. Furthermore, the response does not appear to be able to be predicted on the basis of clinical features of inflammation. It appears that a defined concentration-toxicity relationship exists and should be considered when dosage regimens for patients are formulated. Symptoms occur with a circadian rhythm, and similarly, there is circadian variation in the pharmacokinetic/pharmacodynamic response of a number of NSAIDs in patients with osteoarthritis. Selection of the optimal drug formulation will also be influenced by the need for continuous or intermittent therapy in these patients. PMID- 8194284 TI - The fate of exogenous surfactant in neonates with respiratory distress syndrome. AB - Respiratory distress syndrome (RDS) in newborn neonates is characterised by deficient secretion of surfactant from type III alveolar cells. Administration of surfactant to airways acutely decreases the degree of respiratory failure and increases the survival rate in neonates with RDS. Clinically available surfactants are lipid extracts derived from animal lung lavage or from whole lung. Synthetic surfactants contain phospholipids or additional spreading agents. An optimal exogenous surfactant would be efficacious, nontoxic and nonimmunogenic, resistant to oxidants and proteolytic agents, widely available at reasonable cost and manufactured with little batch-to-batch variability. Surfactant has been instilled into the airways as a bolus infusion through the endotracheal tube. In addition, surfactant may be given by aerosolisation or continuous infusion into the airways. Suggested dosages range from 50 to 200 mg/kg. Exogenous surfactant is cleared from the epithelial lining fluid (ELF) mainly by alveolar epithelial cells, although alveolar macrophages and the central airways may also contribute to clearance of the drug. Only small quantities of surfactant actually enter the blood stream. A significant fraction of surfactant is taken up, processed, and secreted back into the alveolar space by type II alveolar cells. This process is termed recycling. Phosphatidylglycerol, given to small premature neonates as a component of exogenous human surfactant, has an apparent pulmonary half-life of 31 +/- 3 hours (n = 11). The apparent pulmonary half-life of the main surfactant component dipalmitoyl phosphatidylcholine is 45 hours (n = 3) and that of surfactant protein A is about 9 hours (n = 4). A relationship between the dose of exogenous surfactant and its concentration in the ELF has been demonstrated. Some neonates with RDS respond poorly to surfactant therapy. The reasons for this include insufficient levels of surfactant in the ELF, uneven distribution of exogenous surfactant, inability of exogenous surfactant to enter the metabolic pathways, inhibition of surface activity by plasma-derived proteins, or inactivation of surfactant as a result of proteases, phospholipases, or oxygen free radicals. In addition, surfactant therapy may be ineffective in neonates with respiratory failure caused by factors other than surfactant deficiency. The efficacy of exogenous surfactant can be improved by increasing the dosage of surfactant and by administration of surfactant very early in respiratory failure. PMID- 8194286 TI - Physician beliefs, attitudes, and approaches toward Lyme disease in an endemic area. AB - To assess the beliefs and practice habits regarding Lyme disease among practitioners, questionnaires were sent to physicians in a seven-county Lyme endemic region. One hundred twenty-four evaluable responses were returned from 53 family physicians, 39 pediatricians, 27 internists, and five subspecialists who diagnosed three to four cases of Lyme disease per year, on average. The majority presented with erythema migrans (EM) or other early symptoms, although arthritis was the presenting sign in 16%. The enzyme-linked immunosorbent assay (ELISA) was the most frequently ordered diagnostic test, but 45% of respondents did not specify which test when ordering Lyme serology. The majority would use amoxicillin or doxycycline to treat EM in children or adults, respectively. Nearly all would use ceftriaxone for meningitis, and half would use it to treat Lyme arthritis or Bell's palsy. Physicians differed markedly in the duration of therapy they would prescribe. Eighty-three percent would treat a patient for possible Lyme disease with antibiotics (many intravenously), even in the absence of EM or positive serology. Thirty-five percent of practitioners prescribed antibiotics for deer-tick bites. Our survey documents significant variation in approaches to Lyme disease among primary-care physicians and suggests the need for well-designed clinical trials, continuing basic research, and physician education. PMID- 8194287 TI - Use of community health workers with inner-city children who have asthma. AB - Use of community health workers (CHWs) to obtain health, social, and environmental information from African-American inner-city children with asthma was one component of a larger intervention study designed to reduce morbidity in African-American children with asthma. A subset of 140 school-aged children with asthma was recruited and enrolled in a program to receive home visits by CHWs for the purposes of obtaining medical information and teaching basic asthma education to the families. Data obtained by the CHWs revealed low inhaled steroid use, high beta 2 agonist use, frequent emergency-room visits, decreased primary-care visits, and increased allergen and irritant exposure. Appropriately recruited and trained CHWs are effective in obtaining useful medical information from inner city families with children with asthma and providing basic asthma education in the home. PMID- 8194288 TI - Problems with serum IgM as a screening test for congenital infection. AB - The purpose of this study was to determine the usefulness of the total serum IgM level as a screening test for congenital infection in asymptomatic or mildly symptomatic infants. A retrospective medical record review was performed on 168 infants in whom the serum IgM was measured as a screen for congenital infection. The indications for testing, the yield of testing, and the adequacy of follow-up of abnormal values were examined. Only one infant was diagnosed with a congenital infection which was not specifically suspected prior to screening; this was a case of congenital cytomegalovirus (CMV). Inappropriate screening was frequently performed in infants in whom indications for specific evaluation were present. Appropriate follow-up testing was performed in only 30% (seven of 23) of the infants with elevated serum IgM who received their pediatric care at our institution. Because of the low yield (< 1%) and lack of follow-up shown in this study, as well as poor sensitivity, serum IgM was not a useful screening test for congenital infection in our institution. PMID- 8194289 TI - Cardiac function in malnourished children. AB - The cardiovascular status of severely malnourished children was characterized before, during, and after nutritional rehabilitation. In most children with third degree malnutrition, cardiac mass was decreased on admission to the hospital and recovered subsequent to nutritional therapy. All children had echocardiographic and Doppler measurements indicative of impaired ventricular function which significantly improved during the course of hospitalization, as evidenced in part by the change in fractional shortening (P = 0.015), mean velocity of circumferential fiber shortening (P = 0.038), and systolic time interval (P = 0.030). We conclude that children with primary third-degree malnutrition not only have cardiac muscle wasting, but also have inherent ventricular dysfunction as the result of severe malnutrition that responds to nutritional therapy. Particular care with fluid administration is imperative in the first week of therapy, when heart function is the most compromised. PMID- 8194290 TI - Renal vascular abnormalities associated with prenatal cocaine exposure. PMID- 8194291 TI - Cocaine ingestion and abnormalities of the urinary tract. PMID- 8194292 TI - Thrombotic complications in pediatric inflammatory bowel disease. PMID- 8194293 TI - Wegener's granulomatosis presenting as fever of unknown origin. PMID- 8194294 TI - The impact of recent lawsuits on methylphenidate sales. PMID- 8194295 TI - Pericarditis complicating meningococcal meningitis in a 7-month-old boy. PMID- 8194296 TI - Accurate determination of height using an inexpensive measuring device. PMID- 8194297 TI - Lumbosacral plexopathy temporally related to vaccination. PMID- 8194298 TI - Ohmeda Biliblanket vs Wallaby Phototherapy System for the reduction of bilirubin levels in the home-care setting. PMID- 8194299 TI - Sinopulmonary manifestations of congenital bronchobiliary fistula. PMID- 8194301 TI - Repetition blindness between visually different items: the case of pictures and words. AB - Repetition blindness (RB) is the failure to see or recall the second of two visually similar or identical items in rapid serial visual presentation. It was initially demonstrated by Kanwisher (1987), who proposed that a second token of a given word or object type cannot be established when the two items occur close in time. Bavelier and Potter (1992) showed that RB also occurs between visually different items that are phonologically similar. They proposed that RB may occur not only when the targets are physically similar, but also when they have to be registered or encoded in short-term memory (STM) along dimensions on which they are similar. This hypothesis predicts that RB between visually different items should not be restricted to words, but should occur with any stimuli, as long as the task requires these stimuli to be encoded along dimensions on which they are similar. Moreover, it also implies that a task that changes the preferred code of targets will affect the size of RB. The first prediction was confirmed by establishing RB between phonologically similar pictures and words, whether semantically related (the picture of a cat and the word "cat") or not (the picture of a sun and the word "son"), when using a task that requires phonological encoding (Experiments 1 and 2). The second prediction was also supported: the magnitude of RB depended on whether the task required similar or different codes for pictures and words (Experiments 3 and 4). These experiments confirm that RB between visually different items is due to the similarity of the codes initially used in STM. The results suggest that RB can occur at any step during the instantiation of a token, arising not only from a failure to create a new token, but also from a failure to stabilize an opened token. In this view, tokens are to be seen as dynamical entities, built over time as a function of type activation and task requirements, and varying in stability as a function of the information that is entered into them. PMID- 8194300 TI - Perilous life-sustaining therapy and the primary-care physician: should the buck stop there? PMID- 8194302 TI - When prosody fails to cue syntactic structure: 9-month-olds' sensitivity to phonological versus syntactic phrases. AB - According to prosodic bootstrapping accounts of syntax acquisition, language learners use the correlation between syntactic boundaries and prosodic changes (e.g., pausing, vowel lengthening, large increases or decreases in fundamental frequency) to cue the presence and arrangement of syntactic constituents. However, recent linguistic accounts suggest that prosody does not directly reflect syntactic structure but rather is governed by independent prosodic units such as phonological phrases. To examine the implications of this view for the prosodic bootstrapping hypothesis, infants in Experiment 1 were presented with sentences in which pauses were inserted either between the subject noun phrase (NP) and verb or after the verb. Half of the infants heard sentences with lexical NP subjects, in which prosodic structure is consistent with syntactic structure. The other half heard sentences with pronoun subjects, in which prosodic structure does not mirror syntactic structure. In a preferential listening paradigm, infants in the lexical NP condition listened longer to materials containing pauses between the subject and verb, the main syntactic constituents. However, in the pronoun NP condition, infants showed no difference in listening times for the two pause locations. To determine if other sentence types containing pronoun subjects potentially provide information about the syntactic constituency of these elements, infants in Experiment 2 heard yes-no questions with pronoun subjects, in which the prosodic structure reflects the constituency of the subject. Infants listened longer when pauses were inserted between the subject and verb than after the verb. Taken together, our results suggest that the prosodic information in an individual sentence is not always sufficient to assign a syntactic structure. Rather, learners must engage in active inferential processes, using cross-sentence comparisons and other types of information to arrive at the correct syntactic representation. PMID- 8194303 TI - Evidence for a distinct kind of noun. AB - According to traditional accounts of the count/mass distinction, singular count nouns require a determiner. These accounts do not explain why certain count nouns (e.g., "camp" and "church") do not obey that rule. In this paper it is argued that these kinds of nouns are distinct from count nouns and, in fact, are lexical noun phrases. Thus, they are labelled "NP-type nouns". The spontaneous speech of four children and their parents was examined for the use of determiners with NP type nouns and count nouns. It was shown that the parents made a clear distinction between the two kinds of nouns. That is, they omitted determiners with the NP-type nouns, but not with the count nouns. Each of the children made the same distinction by 4 years of age, and in two cases much earlier. Additionally, the children's use of adjectives was examined and it was found that they modified NP-type nouns as if they were noun phrases. It was concluded that NP-type nouns are represented as noun phrases and that children acquire the category as, or before, they acquire the count/mass distinction. The implications for theories of the count/mass distinction were discussed and additional questions concerning learnability and historical change were raised. PMID- 8194304 TI - A computer software for frequential analysis of slow intracranial pressure waves. AB - A microcomputer program to analyse ICP signal in the frequential domain is described. It allows the detection and quantification of especially slow pressure waves (A, B, and C). 212 ICP data recordings were analysed with our software, and gave pertinent frequential informations. The status report and lessons learned are discussed. PMID- 8194305 TI - A new combined integral-light and slit-scan data analysis system (DAS) for flow cytometry. AB - Flow cytometry using list mode parameters such as fluorescence emission, light scatter and size on one hand and different slit-scan parameters on the other hand needs a fast, flexible, efficient and easy-to-use data analysis software. A new software package (data analysis system, DAS) has been developed that integrates data analysis for conventional (integral-light) flow cytometry and for slit-scan flow cytometry. The requirements, design and some examples are discussed and an implementation for IBM-compatible computers is presented. Special attention is directed to the handling of different data types from one-parameter histograms to multiparameter slit-scan data files. The package can be used as an interpreting programming language or as an interactive menu-driven command line interpreter with a large number of graphic, mathematical and statistical functions. DAS is not limited to use in flow cytometry only, but multidimensional data analysis, from astronomy to economics, can be done as well. PMID- 8194306 TI - System to obtain exercise respiratory flow waveforms. AB - A system for obtaining respiratory flow rate waveforms, tidal volume, minute volume, respiration rate, inhalation time and exhalation time is described. The system is based on a microcomputer with analog-to-digital converter board. System software allows calibration, data acquisition and data analysis. Data can be obtained automatically at fixed time intervals. The system is inexpensive and reliable. PMID- 8194307 TI - Elliptic Fourier approximation with application to left ventricular contour analysis. AB - A computer program for the quantitative analysis of left ventricular wall motion, in standard angiography or echography, was developed based on the center-line model. In order to resolve the uncertainties of the previous implementations, the elliptic Fourier approximation was tested on a large set of left ventricular contour pairs, in various pathological conditions. Fitting a function to the center-line (in the middle of end diastolic and end systolic contours) makes it possible to perform multiple tasks at the same time, in an analytical way and without the need of arbitrary parameters, such as search windows. In doing so, the flexibility and accuracy of this method was demonstrated, more in general, for filtering, interpolation and differentiation of noisy 2D or 3D data. A comparison with standard B-spline was carried out, for both open and closed curves, with sparse or equispaced points. The resulting approximation errors were twice as high as those of the elliptic Fourier decomposition, still preserving smooth direction and curvature. Though already described, this methodology deserves more widespread application. PMID- 8194308 TI - A computer program for non-parametric analysis of incomplete repeated measures from two samples. AB - RMNP2 is an easy-to-use FORTRAN program for the analysis of repeated measures using the non-parametric two-sample tests of Wei and Lachin (J. Am. Stat. Assoc. 79 (1984) 653-661) and Wei and Johnson (Biometrika 72 (1985) 359-364). The program compares two groups of subjects or experimental units when measurements are obtained at multiple time points, or under multiple conditions, from each subject. A strength of the methodology is that subjects with missing responses at one or more time points can be included in the analysis, under the assumption that the missing value mechanism is independent of the response. In contrast to other methods that require parametric assumptions concerning the distribution of the outcome variable, RMNP2 is applicable when the response variable is continuous but not normally distributed. The program is also useful in the analysis of ordered categorical outcomes when the number of possible responses is too large to permit application of general categorical data methodology. The program can be run on microcomputers, workstations and mainframe computers. Two examples illustrating the use and features of RMNP2 are provided. PMID- 8194309 TI - Fast algorithms for computing and displaying dose-distributions in tomogram oriented brachy-radiotherapy. AB - This paper describes in detail a dose calculation algorithm tailored to the needs of tomogram-oriented brachy-radiotherapy and a general-purpose dose visualization for displaying the dose distribution as isolines (or rather interval planes). The verbal description of the algorithms is accompanied by structograms. However, the intention of the authors is to present very fast algorithms that are easy to implement and to give a ready-to-use example formulated in 68020 assembler code. Execution times are estimated theoretically by counting clock cycles and practically by measuring the execution time of sample calculations. It turns out that both the dose calculation as well as the visualization algorithm need less than 1 s when applied to a radioactive point source lying on an arbitrary 320 x 256 grid of three-dimensional space. PMID- 8194310 TI - A simple computer programme for biokinetic study of 99Tcm-radiopharmaceuticals. AB - A simple programme has been written in GW BASIC to calculate the percentage activity of 99Tcm-radiopharmaceuticals in different tissues after biodistribution. The programme is efficient, easy to handle and produces a permanent record in terms of a final report. PMID- 8194311 TI - Updating NONMEM IV installation and execution on the VAX 9000: DCL procedure for single-step execution. PMID- 8194312 TI - Converting cardiac surgery patients from dopamine to dobutamine. AB - Dobutamine may benefit normotensive patients with cardiac decompensation due primarily to loss of ventricular contractility or when left ventricular afterload reduction is needed. Dopamine is useful when perfusion pressure must be increased to compensate for loss of vascular tone and hypotension. The bedside nurse often must make crucial drug choices to optimize the patient's hemodynamic status. Table 2 provides an easy reference to this guideline in an algorithm. Even less experienced cardiovascular nurses have been able to apply this tool appropriately. As a standing hospital procedure, approved by our cardiovascular surgeons and related committees, it provides a legal standard whereby the nursing staff can convert from dopamine to dobutamine when the need arises. PMID- 8194313 TI - Margaret L. Campbell: making an end-of-life difference. Interview by Michael Villaire. PMID- 8194314 TI - A comparison of anxiety levels of female and male patients with myocardial infarction. PMID- 8194315 TI - To what extent are you helping your patients and their families in filling out advance directives? PMID- 8194316 TI - Maxing out resuscitation in prehospital cardiac arrest. PMID- 8194317 TI - Time to choose your own critical path. PMID- 8194318 TI - Liver failure: a case study of a complex problem. PMID- 8194319 TI - The involvement of the pulmonary system in liver failure. PMID- 8194320 TI - Request for nursing electronic bulletin boards gets responses. PMID- 8194321 TI - Request for nursing electronic bulletin boards gets responses. PMID- 8194322 TI - Request for nursing electronic bulletin boards gets responses. PMID- 8194323 TI - The gastroepiploic arteries as alternative coronary artery bypass conduits. AB - The indications for GEA grafting may expand due to increased coronary bypass demand and superior patency. The utilization of the right GEA as an alternative conduit may become a future trend for complex CABG patient populations. Nurses must document more cases and conduct more research to guide future nursing actions. PMID- 8194324 TI - Use of a hemoglobin substitute in the anemic Jehovah's Witness patient. AB - Fluosol DA is an experimental means of supplementing oxygen delivery in the anemic patient. The drug's ability to improve oxygen transport appears to improve SVO2. Blood transfusion is the first choice for acute anemia secondary to hemorrhage; however, perfluorochemicals offer an alternative for the patient who cannot accept transfusion therapy. This article reports a case of severe anemia in which transfusion was refused because of the patient's religious convictions. Perfluorochemicals represented an effective medical treatment that was compatible with this patient's religious beliefs. Continued research in artificial oxygen transporters may lead to even more effective drugs for the treatment of acute anemia, possibly decreasing the need for blood transfusion for all patients. PMID- 8194325 TI - Informational support for families immediately after CABG surgery. PMID- 8194326 TI - Patient perception of preoperative cardiac surgical teaching done pre- and postadmission. AB - Preoperative cardiac surgical teaching done on a preadmission vs postadmission basis did not affect subjects' perception of importance of preoperative information or preparation. Hospital teaching methods must be examined so that patient learning is individualized and available when the patient is ready to learn. Preoperative teaching on a preadmission basis may also facilitate admission of the cardiac surgical patient the day of surgery, which could shorten the length of stay. PMID- 8194327 TI - Directional coronary atherectomy: a new treatment for coronary artery disease. PMID- 8194328 TI - Approaches and limitations of medication delivery in patients with enteral feeding tubes. AB - The hypertonicity of liquid medications must be evaluated in conjunction with the required dosage volume. Some medications require a minimal dosing volume and can be adequately diluted in gastric fluids or tube-flush volumes to a tolerable osmotic load. Other medications such as diphenoxylate, loperamide, and paregoric have a pharmacologic influence on motility and can be administered undiluted into the small bowel. Still others can require dilution to a final volume of 4 to 10 oz to reduce osmolality to a level tolerable by the GI tract. Bolus administration of a large volume of medication is impractical for many patients, especially if it must be administered three or four times a day. For these patients, an alternate route of drug administration is often preferable. In some instances, the IV route is most appropriate. In others, crushing the appropriate oral form, mixing it in a slurry with a suitable diluent, and administering the slurry through the feeding or NG tube can be an acceptable alternative. Regardless of the method of drug delivery, one must be cognizant of the limitations of the administration strategy, the potential for complications that can result from the administration of a medication by the enteral route, and alternative means of medication administration, should complications ensue. A vast number of pharmaceutical products are marketed in a wide array of dosage forms. For these reasons, a pharmacist or other knowledgeable healthcare provider should be consulted for information regarding product availability, bioavailability, compatibility, and potential for drug-nutrient interactions when drugs are given in conjunction with enteral feeding. PMID- 8194329 TI - Pathophysiologic changes associated with atrial septal defects: a case report. PMID- 8194330 TI - Malignant vasovagal syncope after PTCA: a potential for disaster. PMID- 8194331 TI - Open vs closed-system endotracheal suctioning: a cost comparison. PMID- 8194332 TI - The critical care nurse as patient advocate. PMID- 8194334 TI - Support groups: an annotated bibliography for critical care nurses. PMID- 8194333 TI - Basic knowledge assessment tool for critical care nursing, version four (BKAT-4): validity, reliability, and replication. PMID- 8194336 TI - Tony Tripp-Reimer--crossing over the boundaries. Interview by Michael Villaire. PMID- 8194335 TI - Waiting and wanting: helping families in crisis. PMID- 8194337 TI - The patient-driven system. PMID- 8194338 TI - Drawing blood from central lines--concern about infection control. PMID- 8194339 TI - A look behind the mask of impostorship. PMID- 8194340 TI - Muscle relaxants article was appreciated; additional comments offered. PMID- 8194341 TI - Muscle relaxants article was appreciated; additional comments offered. PMID- 8194342 TI - Muscle relaxants article was appreciated; additional comments offered. PMID- 8194343 TI - Other voices respond to Endnote on 'organ brokers'. PMID- 8194344 TI - Other voices respond to Endnote on 'organ brokers'. PMID- 8194345 TI - Other voices respond to Endnote on 'organ brokers'. PMID- 8194346 TI - Determining if vasovagal syncope is 'malignant' not as important as treatment. PMID- 8194347 TI - Disagree with view against pulling chest tubes. PMID- 8194348 TI - Diagnosis and management of arrhythmias associated with Wolff-Parkinson-White syndrome. AB - Because of the emergency nature of the arrhythmias associated with WPW syndrome, nurses are often called upon for diagnosis and intervention in critical settings. In such cases the nurse's understanding of mechanisms, ECG recognition, and emergency treatment guarantees the patient the best possible outcome, not only in the critical setting, but in the long term as well. The most common arrhythmias of WPW syndrome are PSVT and atrial fibrillation. In PSVT a differential diagnosis is made on the ECG between (1) CMT using the AV node anterogradely and an accessory pathway retrogradely and (2) AV nodal reentry tachycardia. Helpful clues are location of the P' wave, presence of QRS alternans, the initiating P'R interval, and presence of aberrancy. Atrial fibrillation with an accessory pathway has the morphology of VT but is differentiated because the rhythm is irregular and the rate is more than 200 beats per minute. Emergency treatment consists of blocking the accessory pathway with procainamide. Emergency treatment for both types of PSVT consists of breaking the reentry circuit at the AV node (eg, vagal maneuver, adenosine, or verapamil). Procainamide can also be used to block the retrograde fast pathway in the AV node and to terminate CMT by blocking the accessory pathway. Symptomatic patients with accessory pathways are referred for evaluation and possible radio-frequency ablation. PMID- 8194349 TI - Addiction to surgery: a nursing dilemma. AB - Factitious disorder is either a rare or underdiagnosed disorder and therefore, not one the nursing staff anticipates. Once the disorder is diagnosed, the intense feelings of the nursing staff may overwhelm them. Therefore, the staff should be able to participate in discussion sessions conducted by a psychiatric clinical nurse specialist or another qualified person. Such sessions should focus on recognition of feelings, comparison of one's feelings with those of other staff members, and sharing of perceptions about the situation. PMID- 8194350 TI - Assessing the five points of the intra-aortic balloon pump waveform. AB - IABP timing challenges the nurse not only with a waveform analysis but also an understanding of complex physiologic concepts crucial to patient management. Optimizing timing through assessment of the five points of the IABP waveform permits the critical care nurse to increase the hemodynamic benefits of IABP therapy, potentially improving patient outcome. PMID- 8194351 TI - Transesophageal echocardiography: implications for the critical care nurse. AB - TEE is an exciting and useful diagnostic tool that is rapidly gaining widespread acceptance in both teaching centers and community hospitals. Because of the semi invasive nature of the procedure, nursing expertise is essential to ensure patient safety and comfort during the TEE examination. PMID- 8194352 TI - Pulmonary artery catheter removal. PMID- 8194353 TI - No flowers in the CCU. PMID- 8194354 TI - Identified needs of parents in a pediatric intensive care unit. PMID- 8194355 TI - Percutaneous laser myoplasty: nursing care implications. PMID- 8194356 TI - Localization and characterization of binding sites for endothelin in Harder's gland in rabbits. AB - The characterization and localization of binding sites for endothelin-1 (ET-1) labeled with iodine 125I were investigated in homogenized tissues and sections of Harder's glands of normal rabbits. The membrane of Harder's glands was harvested and incubated with 125I-ET-1 (0.25-1 nmol/L) in 20 +/- 4 mg of protein per 0.25 mL at 37 degrees C for 90 min in the presence of protease inhibitors. Specific labeling was assessed by coincubating unlabeled ET-1, ET-2, ET-3 and other unrelated cytokines. The tissue labeled with 125I-ET-1 was collected by filtration and counted in a gamma counter. For an in vitro autoradiography study, 15 microns cryostat sections were incubated with 125I-ET-1 (0.1 nmol/L). They were fixed, dipped in liquid emulsion and kept for 6 days before development. Membrane counting showed that the binding of 125I-ET-1 to Harder's gland was saturable. Scatchard data analysis revealed one class of binding with a dissociation constant (Kd) of 0.33 nmol/L and a maximal density of binding (Bmax) of 794 attomole/mg of protein. The binding was inhibited most by ET-1, followed by ET-2 and then ET-3 but not by unrelated peptides. Emulsion-dipped slides with sections showed specific high-density labeling mainly over structures identified from serial sections stained by hematoxylin-eosin as the walls of capillaries, arterioles, arteries, and veins of the glands. Less dense binding was found in both white and pink lobes of the gland. No binding was found in fat and connective tissues. The distribution of endothelin action sites in the glandular blood vessels and Harder's gland suggests that the peptide may have a role in the regulation of blood circulation and glandular secretion in the normal rabbit. PMID- 8194357 TI - Nucleoside transport sites in a cultured human retinal cell line established by SV-40 T antigen gene. AB - Adenosine, an important neuromodulatory compound in the brain and retina, is a potent vasodilator in most vascular beds throughout the body. Its actions are potentiated by inhibitors of nucleoside transport into cells. Knowledge of the existence of specific adenosine uptake systems in mammalian retina and the inhibition of the uptake by nitrobenzylthioinosine (NBMPR), a potent inhibitor of nucleoside transport, raises the possibility that the associated nucleoside transport system may be of pharmacological importance in retinal function. We have characterized the binding of the nucleoside transporter probe, [3H]NBMPR, to a cultured human retinal cell line established by transfection of SV-40 T antigen plasmid-DNA. The binding was specific, saturable and reversible. Scatchard analysis of the saturation data revealed that NBMPR binds to a homogeneous population of high affinity binding sites (KD = 0.65 +/- 0.22 nM; Bmax = 466 +/- 157 fmol/mg protein) characteristically similar to the binding sites in human retinal tissue (KD = 0.32 +/- 0.01 nM; Bmax = 292 +/- 41 fmol/mg protein). Selected compounds inhibited the binding in the cell line and retinal tissue with the same rank order of potency, suggesting that the transporters in the cell line and retinal tissue are similar. The data showed that the cell line is a useful model for the study of nucleoside transporter function in human retina. PMID- 8194358 TI - Relationship between morphometric optic disc parameters, sex and axial length. AB - Optic disc correlations were evaluated in normal eyes by means of computer-aided morphometry. Two hundred and thirty-five subjects (144 women and 91 men) entered the study. One eye per patient was randomly chosen for statistical analysis. Disc area (P < 0.05) and axial length (P < 0.0001) were statistically different between sexes. There was a correlation between axial length and both disc area (r for females = 0.55, P < 0.00001; r for males = 0.35, P < 0.0007) and refraction (r for females = 0.40, P < 0.00001; r for males = 0.50, P < 0.00001). The main findings of this investigation were that disc area is greater in male than in female eyes (thus clinically confirming the Ishi's and Quigley's previous observations of autopsy eyes) on the basis of axial length difference between the two sexes, and that disc size correlated with axial length. Disagreements in disc measurements reported in previous studies may be caused by differences in the male/female ratios of their samples. PMID- 8194359 TI - Immunohistochemical insights into sickle cell retinopathy. AB - Dynamic vaso-occlusive and vaso-proliferative events occur in sickle cell retinopathy. Using streptavidin peroxidase immunohistochemistry, we investigated changes in distribution and relative levels of components in the fibrinolytic system and growth factors in retina and choroid from 2 sickle cell patients: a 20 month old SS patient and a 54 year old SC patient. Antigen localization in the sickle cell patients was compared to localization from 2 non-sickle cell, non diabetic control subjects. In the fibrinolytic system, tissue plasminogen activator (tPA) localization and immunoreactivity were comparable in all eyes, but plasminogen activator inhibitor-1 (PAI-1) immunoreactivity was elevated within the walls of retinal vessels in the sickle cell tissue. Immunoreactive fibrin was often observed within the lumen of retinal and choroidal vessels and in choroidal neo-vascularization (CNV) in sickle cell subjects. Blood vessels containing fibrin generally exhibited elevated PAI-1 immunoreactivity. Von Willebrand's factor (vWf) and basic fibroblast growth factor (bFGF) immunoreactivity in sickle cell patients were elevated in choriocapillaris and the walls of some retinal vessels. Transforming growth factor-beta 1 (TGF-beta 1) immunoreactivity was significantly lower in sickle cell choriocapillaris than in controls. In chorioretinal pigmented lesions of the SC patient, bFGF and TGF-beta 1, beta 2, and beta 3 immunoreactivity was present within migrating retinal pigment epithelial (RPE) cells. Our interpretation of the data presented in this case study is that fibrin deposition within retinal and choroidal vessels of sickle cell subjects may occur due to elevated PAI-1 activity. Moreover, vaso occlusions of choroidal vessels may influence the expression of growth factors in choriocapillaris endothelium, which could stimulate formation of choroidal neovascularization. Finally, fibrosis and gliosis in and near chorioretinal pigmented lesions may be stimulated by RPE production of bFGF and TGF-beta's. PMID- 8194360 TI - A platelet-activating factor antagonist reduces corneal allograft inflammation and neovascularization. AB - We assessed the role of platelet-activating factor (PAF) in corneal allograft rejection and evaluated the effects of a PAF antagonist on corneal inflammation, cellular infiltration, vascularization, and edema. Rabbits with vascularized corneas served as recipients of allogeneic cornea grafts. Rabbits with normal corneas underwent autografts as controls. All of the allografts developed the progression of signs characteristic of rejection. Nevertheless, treatment with the PAF antagonist BN52021 significantly inhibited corneal allograft vascularization for up to 10 days after transplantation and reduced the number of eosinophils in the allografts at 28 days after transplantation. In contrast, saline-treated allografts exhibited florid vascularization and intense inflammatory infiltrates. Control autografts survived without developing significant inflammation or vascularization. The retardation of allograft eosinophilia and graft vascularization by the PAF antagonist was most likely the result of suppression of PAF-mediated reactions in the cornea. These results indicate that PAF may play a role in corneal inflammation and vascularization after corneal transplantation, and that PAF antagonists may be clinically useful in delaying some of the pathophysiologic consequences of corneal graft rejection. PMID- 8194361 TI - Immunolocalization of PKC zeta in rat photoreceptor inner segments. AB - We have utilized several peptide specific antisera directed against the C terminals (Wetsel et al, 1992) of several protein kinase C (PKC) isozymes (alpha, beta 1, beta 11, gamma, delta, epsilon, zeta) to delineate the cellular localization of these PKC isozymes in rat retina. Antisera against PKC beta 1, beta 11, gamma, delta and epsilon were non-reactive in frozen rat retina sections, whereas, anti PKC alpha was strongly reactive with the outer plexiform, inner plexiform and nerve fiber cell layers. The most specific localization of immunoreactivity was observed with PKC zeta, which reacted strongly and exclusively with photoreceptor inner segments, but not outer segments. Immunoblot analysis of whole rat retina homogenate showed that anti-PKC alpha recognized an antigen of approximately 80kD and anti-PKC zeta recognized a approximately 72kD protein. Immunolocalization of PKC zeta to photoreceptor inner segments and possible functional significance are discussed. PMID- 8194362 TI - 31P magnetic resonance spectroscopy after combined hyperthermia and radiation. AB - Mechanisms of uveal melanoma response to therapy are poorly understood. There are a paucity of changes that have been detected immediately after tumor treatment to differentiate successful from ineffective therapy. In this study we used in vivo 31P magnetic resonance spectroscopy (MRS) to assess intra-tumor treatment alterations. The metabolic consequences of effective and ineffective levels of solitary hyperthermia and combined hyperthermia-radiation were investigated. We have previously noted a characteristic 31P MRS pattern with successful hyperthermia in this intraocular melanoma model. The metabolic response after effective or ineffective combined radiation/hyperthermia therapy was indistinguishable from solitary radiation therapy and opposite to that with successful hyperthermia therapy. In contrast to solitary hyperthermia therapy, early changes in 31P spectral ratios following radiation or combined hyperthermia/radiation therapy of uveal melanoma were not predictive of treatment response. Twenty-four to 48 hours after effective or ineffective radiation or combined treatment the Pi/beta-NTP ratio decreased significantly (delta Pi/beta NTP = -0.433 +/- 0.08 and -0.478 +/- .13 and .10 +/- 0.2, respectively). There was over a 2.0 thermal enhancement of radiation with heat. The increased tumor cell death after combined therapy was reflected by a two-fold larger decrease in beta-NTP signal-to-noise (S/N). PMID- 8194363 TI - A new procedure for fundus photography and fluorescein angiography in small laboratory animal eyes. AB - Increasing interest in retinal research demands continuous improvement of experimental techniques and interpretation. Thus, the purpose of our research was to devise a new method for funduscopic photography and fluorescein angiography in the normal or diseased retina of the small laboratory animal that would produce results comparable in optical quality and field coverage to those obtained in human clinical practice. To enhance the view of the small eye, a 2.2 Volk Panretinal lens was held in apposition to the lens of a clinical fundus camera, the Topcon TRC 50FT, by means of a custom made metal sleeve. Albino mice, albino rats, and pigmented rats were photographed. Fluorescein angiography was performed on pigmented rats. Fluorescein was administered intravenously via the jugular vein at a dose of 5 mg/kg. Various speeds of film and flash settings were used depending on the light source and the pigmentation of the animal. Attachment of the 2.2 Panretinal lens to the clinical fundus camera allowed for more clearly defined fundus photographs of the small laboratory animal, as well as an enlarged field of observation over conventional techniques. Consequently, angiography fields and stages documented in the small laboratory animal approximated those obtained in human clinical practice. This technique facilitates the visualization of small fundi and it allows for a fuller documentation of experimental retinal models. PMID- 8194364 TI - Effects of dextromethorphan on ischemia induced electroretinogram changes in rabbit. AB - The present study was undertaken to determine whether dextromethorphan (DM), a potent N-methyl-D-aspartate antagonist, could attenuate the effects of ischemia on rabbit ERG. Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for 30, 60, or 90 min. DM was intravenously administered before ischemia and maintained throughout the entire experimental period. ERGs were recorded prior to, during, and after ischemia. The results indicate that the b wave hyperresponses and the delays in implicit times induced by 30 min. ischemia were suppressed by the administration of DM. Similar findings were obtained when ischemia lasted for 60 min, except that DM did not improve delayed implicit times, suggesting that cellular injury is still present. ERG changes resulting from 90 min ischemia were not reversed by DM treatment. Effects of DM treatment on a-wave were less prominent. Together, our results further support that DM can to some extent alleviate ischemic injury in the rabbit retina. PMID- 8194365 TI - Feasibility of drug targeting to the retinal pigment epithelium with biodegradable microspheres. AB - There are several systems of delivering drugs to cells with phagocytic activity. We studied the possibility of targeting drugs to retinal pigment epithelial (RPE) cells with the use of surface-modified microspheres. A fluorescent dye, 1,4-bis[2 (5-phenyloxazolyl)]-benzene (POPOP), was incorporated into microspheres of poly(lactic acid) for use as a marker to evaluate drug delivery. Phagocytosis of the microspheres, with or without gelatin precoating, was carried out at 37 degrees C and 4 degrees C. The cell-incorporated fluorescence of POPOP was measured, and scanning electron microscopy was used to confirm phagocytosis. At 4 degrees C, no uptake of POPOP was noted; however at 37 degrees C, cell-associated fluorescence was observed to increase for up to 24 hr. In comparison with bare microspheres, gelatin precoating significantly enhanced phagocytosis (P < 0.001) at the same incubation times. These results suggested that drug delivery to RPE cells may be feasible by means of surface-modified polymer microspheres. PMID- 8194366 TI - Ocular absorption of cyclosporine A from liposomes incorporated into collagen shields. AB - We investigated the ability of liposomes to deliver the immunosuppressive agent cyclosporine A (CsA) to the cornea, anterior sclera, aqueous humor, and vitreous in rabbit eyes. One drop (10 microliters) of liposome-encapsulated CsA (CsA-LIP) or olive oil drops containing an equivalent concentration of CsA (CsA-DR) were administered at 15-minute intervals within the first hour and then one hourly over a 6-hour period. In addition, collagen shields soaked for 30 minutes in the liposome preparation (CsA-LIP-CS) were tested in vitro and in vivo as a new drug delivery approach. CsA levels were measured by fluorescence-immunoassay after 1, 3, or 6 hours of drug administration. CsA levels in this study were highest in cornea and anterior sclera. In animals receiving either CsA-DR or CsA-LIP, CsA levels generally increased from 1 to 6 hours. In animals receiving a single application of CsA-CS-LIP, CsA levels peaked at 3 hours and declined at 6 hours in cornea and sclera. CsA-LIP and CsA-CS-LIP delivered significantly higher levels of CsA to the cornea and sclera at 1 and 3 hours than CsA-DR. In aqueous and vitreous humor, CsA levels increased from 1 to 6 hours in animals receiving either CsA-DR or CsA-LIP. On the other hand, animals receiving a single application of CsA-CS-LIP had lower levels of CsA at 6 hours than at the earlier time points. Animals receiving CsA-LIP or CsA-CS-LIP had significantly higher levels of CsA in aqueous and vitreous humor at 1, 3, and 6 hours than animals receiving CsA-DR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194367 TI - Effects of endothelin-1 on [Ca2+]i and pHi in trabecular meshwork cells. AB - We examined the effects of endothelin-1 (ET-1) on [Ca2+]i and intracellular pH in cultured bovine trabecular meshwork cells and compared the effects of ET-1 with those of angiotensin II (another phospholipase C activating peptide). [Ca2+]i was measured with the Ca2+ fluorescent dye indo-1. Intracellular pH was measured using the pH sensitive fluorescent dye BCECF. Exposure to ET-1 (10 nM) produced a transient increase in [Ca2+]i (from 77.3 +/- 17.3 nM to 503.0 +/- 64.8 nM, p < 0.05, n = 12). Intracellular pH was also increased during exposure to 10 nM ET-1 (+0.081 unit, p < 0.05, n = 6). In the presence of 10 microM EIPA, ET-1 (10 nM) did not change intracellular pH. Angiotensin II did not significantly change [Ca2+]i or intracellular pH. These results suggest that ET-1 may be involved in the regulation of aqueous humor dynamics by changing [Ca2+]i and intracellular pH in trabecular meshwork cells. PMID- 8194368 TI - Epithelial wound healing in the denervated cornea. AB - We studied the epithelial healing of denervated corneas in New Zealand albino rabbits with their left trigeminal ganglia surgically amputated. On the 14th day after amputation, the corneas were keratectomized (in 8.5 mm diameter) and documentation of the healing process began. We calculated the epithelial healing rate using simple regression analysis. We observed a mean healing rate of 0.463 +/- 0.059 mm2/hr (mean +/- SE) in the denervated corneas, compared to 0.609 +/- 0.031 mm2/hr in the control corneas; a statistically significant difference of P < 0.001. We performed scanning electron microscopic observation (SEM) at three points; before keratectomy, 48 hrs after keratectomy, and 14 days after keratectomy. SEM observation revealed that, in contrast to the control corneas, the surface of the epithelial cells in denervated corneas appeared rough with numerous exfoliating cells observed. This indicates that the epithelial cells might attach only weakly to the floor in denervated corneas. Transmission electron microscopic observation (TEM) performed at 48 hrs and 14 days after keratectomy also supports this finding. For example, the intercellular space is widened and fewer desmosomes are observed in denervated corneas. Using immunohistochemistry, the surface of the wound bed was covered with fibronectin in a similar fashion to the control. In the late stage, the denervated corneas demonstrated spontaneous epithelial breakdown with 83% of them having persistent epithelial defects. Epithelial healing in the control corneas displayed no abnormal signs. On the 14th day after keratectomy, these eyes were enucleated for immunohistochemistry using bromodeoxyuridine (Brd U) to observe dividing cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194369 TI - Interferon-gamma induces high-affinity transforming growth factor-beta receptor expression on human corneal fibroblasts. AB - The effect of interferon-gamma (IFN-gamma) on the expression of transforming growth factor-beta (TGF-beta) receptors on cultured human corneal stromal fibroblasts was examined. Scatchard analysis of specific saturable TGF-beta 1 binding data indicated that corneal fibroblasts expressed TGF-beta receptors with an average association constant of 6 x 10 M-1, before and after IFN-gamma treatment. An additional population of higher affinity TGF-beta receptors, with an average association constant of 4 x 10(12) M-1, was demonstrated only on IFN gamma-treated corneal fibroblasts Interferon-gamma may alter the response of corneal fibroblasts to transforming growth factor-betas by upregulating their higher affinity TGF-beta receptors. The induction of higher affinity TGF-beta receptors by an immune cytokine and an associated autocrine elevation of TGF-beta output by the corneal fibroblasts may be a transient compensatory mechanism that maintains the homeostasis of corneal optical competency through enhancement of corneal immunoseclusion. PMID- 8194370 TI - Calmodulin antagonists induce changes in lens permeability and transparency. AB - Calmodulin has been shown to perform several important functions in the lens including regulation of the plasma membrane Ca(2+)-ATPase. This study investigated the effects of a variety of different CaM antagonists on rat lens membrane potential, membrane resistance, intracellular Na+ and Ca2+ content and transparency, in order to examine the role of CaM in control of lens membrane permeability. W7, calmidazolium and trifluoperazine caused biphasic changes in lens membrane electrical characteristics. Phase 1 consisted of a depolarization of the membrane potential and an increase in resistance, indicating that K+ channels were being blocked. This was confirmed by application of the K+ channel antagonist, quinine, which inhibited Phase 1 changes. Phase 2 was a further depolarization coupled with a decrease in resistance, indicating the activation of a cation conductance. Application of W7 in low Na+ medium slowed the Phase 2 depolarization and decrease in resistance indicating that Na+ is the main charge carrier through the activated conductance. The CaM inhibitors also led to a large increase in the Na+ and Ca2+ contents of the lens. W5, a less potent analogue of W7, caused a depolarization and increase in membrane resistance, but no Phase 2 changes were observed. Na+ and Ca2+ contents were similar to control lenses after 4 hours incubation in 200 microM W5. In addition, exposure to W7, TFP and calmidazolium resulted in a loss of transparency, while W5 treated lenses remained clear. It appears, therefore, that CaM is involved in control of lens membrane permeability. Loss of control of these channels leads to catastrophic changes in the intracellular ionic environment and hence opacification of the lens. PMID- 8194371 TI - On the interaction of alpha-crystallin with membranes. AB - The interaction of human and bovine alpha-crystallins with bovine lens membranes was evaluated using binding curves and Scatchard plots constructed from scans of SDS-PAGE gels and/or from the association of [14C]-leu alpha-crystallin with the membranes. No differences were observed for total bovine, normal human 19 and 88 year old and cataractous alpha-crystallins. In each case, interaction takes place through two distinct processes, a) a high affinity (Kd = 1 x 10(-8) M) binding with low capacity (25 mg alpha-crystallin/g membrane protein) and b) partitioning (Kp = 0.25 l/g membrane protein). Loss of the high-affinity binding component was observed for bovine nuclear alpha-crystallin. Contrary to previous reports, it is concluded that cataract formation does not affect the ability of human alpha crystallins to interact with bovine lens membranes. Reanalysis of previously published data supports this conclusion. PMID- 8194372 TI - Activation of phospholipase D by guanosine 5'[gamma-thio]triphosphate and AlF4- in bovine corneal epithelial cells. AB - We have investigated the regulation of phospholipase D (PLD) by guanine nucleotides and AlF4- in bovine corneal epithelial cells (BCEC) prelabeled with [3H]myristic acid. In the presence of ethanol, AlF4- increased the production of [3H]PA and [3H]PET indicating activation of PLD in these cells. The effects of AlF4- were time- and dose-dependent. Addition of guanosine 5[gamma thio]triphosphate (GTP gamma S), to streptolysin O-permeabilized cells also resulted in increased accumulation of [3H]PA and [3H]PEt. Other guanine and adenine nucleotides were ineffective, and guanosine thiodiphosphate inhibited the GTP gamma S-induced activation of PLD. Direct addition of GTP gamma S to microsomal fraction prepared from [3H]myristate-labeled BCEC resulted in increased formation of [3H]PEt in a time- and dose-dependent manner. The activation of PLD by GTP gamma S in the microsomal fraction was absolutely dependent on the presence of Ca2+ > 0.5 microM. Addition of Ca2+ (10-100 microM) alone dose-dependently stimulated the PLD activity. Treatment of the microsomal fraction with phorbol esters had no effect on the ability of GTP gamma S to stimulate PLD. Addition of isoproterenol to BCEC resulted in several-fold stimulation of cAMP, but it had no effect on basal or PDBu-induced stimulation of PLD. Taken together, the data suggest that a GTP-binding protein is involved in regulation of PLD in BCEC, and that maximal stimulation of PLD probably results from an interaction between Ca2+, PKC and G-protein in BCEC. PMID- 8194373 TI - Effect of pH on the bioenergetics of perfused porcine lenses. AB - Extracellular and intracellular pH has been shown to be an important physiological variable in many biological systems. However, studies on the effect of pH on the metabolic status of the mammalian lens have been few. It has been shown previously that a change in perfusate pH has a significant effect on the lens weight, ion transport, opacification and membrane potential. In this study we show that the bioenergetic status of the perfused pig lens, as assessed by 31P NMR spectroscopy, is critically dependent on the pH of the bathing medium. At pH's of 7.6 and above, these perfused lenses maintained their nucleotide triphosphates concentrations steady for up to 4 days. In contrast, lenses perfused with identical media at pH 7.0, rapidly lost their nucleotide triphosphates. Our findings suggest that the pH of the extracellular pH may be an important parameter in maintaining the functional competence of the lens. PMID- 8194374 TI - Enterocutaneous fistulas. PMID- 8194375 TI - Cat-scratch disease encephalopathy. AB - We report five cases of cat-scratch disease encephalopathy (CSDE), with a brief review of the literature in English, in which only 96 patients of CSDE have been described up to the present. The Gram-negative bacilli demonstrated by Warthin Starry or Dieterle silver stains are regarded as the causative agent of CSDE. Administration of antibiotics is recommended. The onset of CSDE is usually acute and the prognosis favorable. PMID- 8194376 TI - CCK receptor antagonist L-365,260 potentiated electroacupuncture analgesia in Wistar rats but not in audiogenic epileptic rats. AB - Cholecystokinin octapeptide (CCK-8) has been shown to be a neuropeptide with potent anti-opioid activity. Previous studies have shown that central administration of nanogram dose of CCK-8 totally abolished morphine analgesia in the rat, an effect mediated by CCK-B receptor in central nervous system. In the present study CCK-B antagonist L-365,260 was injected intracerebroventricularly (icv) to Wistar rats to see its effect on the analgesic effect induced by electroacupuncture (EA) stimulation. A marked potentiation of EA-induced analgesia was observed. The degree of potentiation depends on the frequency of EA used, with a rank order of 100 Hz > 15 Hz = 2/15 Hz > > 2 Hz. In a strain of rat with acoustically evoked epileptic seizure (P77PMC rats), an extra-ordinarily strong analgesic effect was produced in response to 100 Hz EA stimulation, which was similar to that in Wistar rats pre-treated with L-365,260. However, L-365,260 was not effective in potentiating EA analgesia in P77PMC rats. The results suggest that (1) high frequency EA is more likely to increase the release of CCK 8 in CNS as compared to low frequency EA, and (2) P77PMC rats may have a functional defect of the central CCK neurons in the nature of either a low CCK content or a reduced rate of release of CCK-8 in the CNS. PMID- 8194377 TI - Pathological changes of the retrosplenial cortex in senile dementia of Alzheimer type. AB - Six brains of patients aged from 71 to 85 years of clinically and pathologically diagnosed senile dementia of Alzheimer type and six brains of age-matched controls (55-91 years) was used for this study. The retrosplenial cortex of these brains have been examined by Gallyas and Campbell-silver impregnations. Gallyas preparation showed a number of intracellular pathological changes in retrosplenial cortex of demented individuals. Although the neuritic plaques, the neurofibrillary tangles and neuropil threads were seen in all lamina, their high density appear in lamina IIIa and V of retrosplenialis lateralis (Rsl), retrosplenialis intermedia (Rsi), retrosplenialis media (Rsm) and parasplenialis (Ps). The retrosplenial cortex of non-demented individuals was almost devoid of neurofibrillary changes. The retrosplenial cortex of all demented individuals and one age-matched controls showed a large amount of amyloid deposits in Campbell preparation, while two non-demented individuals showed only small amounts of amyloid. The amyloid deposition can be classified into three types. The packing of Campbell-argyrophilic material show area-specific and lamina-specific distribution. PMID- 8194378 TI - National field trial of the Chinese classification and diagnostic criteria of mental disorders: comprehensibility, acceptability and applicability. AB - The Chinese Neurology and Psychiatry Association conducted a national field trial of its Chinese Classification and Diagnostic Criteria of Mental Disorders (CCMD 2) involving 26 provinces and municipalities, 80 psychiatric institutes, and 224 professionals. The results were as follows: (1) 95.2% of researchers considered the comprehensibility of the CCMD-2 diagnostic criteria good. Within the ten major categories, comprehensibility ranged from 85.7% to 100%. (2) Of those surveyed concerning the acceptability of the CCMD-2 diagnostic criteria, 85.9% considered them acceptable. In individual classifications, the rate ranged from 74.1% to 95.2%. (3) 1498 cases were tested. The overall applicability rate which indicated the consistency between the CCMD-2 result and the actual clinical diagnoses was found to be 87.6%, (averaging Kappa = 0.82, P < 0.01), better than those obtained from non-Chinese systems of diagnosis. PMID- 8194379 TI - Reconstruction of esophagus with whole stomach through esophageal bed after resection of the upper esophageal carcinoma. A report of 160 cases. AB - From September 1985 to December 1992, 160 cases of reconstruction of the esophagus with the whole stomach through the esophageal bed after resection of the upper esophageal carcinoma were performed with neither operative mortality nor intrathoracic complications. The leakage rate of the cervical anastomosis with Gambee's single layer method was 1.2%. The main steps of the operative procedure consisted of: (1) making a right thoracotomy for dissecting and removing the entire thoracic esophagus; (2) laparotomy for mobilizing the whole stomach, constricting it to tube shape and doing a pyloroplasty; and (3) pulling up the mobilized tube-like stomach through the posterior mediastinal space (i.e. the esophageal bed) out of the left neck incision and then the esophagogastrostomy with Gambee's single layer anastomosis was performed. PMID- 8194380 TI - Apolipoprotein (a) phenotypes in cardio-cerebrovascular diseases. AB - Apolipoprotein (a) [Lp(a)] phenotypes of 69 myocardial infarction survivor and 56 stroke patients were reported and compared to those of 190 healthy Chinese. The results revealed that the distributions of apo(a) phenotype frequency in patients with cardio-cerebrovascular disease (CCVD) were different from those of controls. The frequency of the phenotypes S1 and S2 were remarkably higher in patients than in controls within the same single-band apo(a) phenotype. Moreover, the Lp (a) serum concentrations in CCVD patients were significantly higher than in controls within the same single-band apo (a) phenotype. The apo (a) phenotype analysis of two pedigrees were shown as a typical autosomal dominant inheritance. PMID- 8194381 TI - Experimental study on pulmonary injury related to oxygen-derived free radicals in acute necrotizing pancreatitis in dogs. AB - It is postulated the pulmonary injury in acute necrotizing pancreatitis could be due to oxygen-derived free radicals released during the attack of acute pancreatitis. To elucidate the relationship between oxygen-derived free-radicals and the degree of pulmonary injury in acute necrotizing pancreatitis, lipid peroxide (LPO) in lung tissues, bronchoalveolar lavage fluid and serum were measured in 10 adult Mongrel dogs with acute necrotizing pancreatitis induced by injection of 5% sodium taurocholate into the pancreatic duct. Compared with the controls (n = 10), the weight of lung was increased (241.2 +/- 33.7 g vs 121.2 +/ 51.4 g, P < 0.05). LPO of bronchoalveolar lavage fluid (BALF) was higher (3.56 +/- 1.64 mumol/L vs 0.75 +/- 0.31 mumol/L, P < 0.05), LPO in peripheral and portal vein 10 hours after induction of acute pancreatitis was also significantly increased. The LPO content of lung tissue was not higher than that of the control group, but hemorrhage within alveolar space and infiltration by polymorphonuclear and phagocytic cells was seen on histological examination. In conclusion, lipid peroxidation could be an important cause of pulmonary injury in acute necrotising pancreatitis. PMID- 8194382 TI - Some humoral factors and their interaction on acute hypoxic pulmonary pressor response. AB - To determine the effect of humoral factors and their interaction on the development of acute hypoxic pulmonary pressor response (HPPR), we performed studies in 16 mongrel dogs. We measured plasma levels of noradrenaline (NE), angiotensin II (AII), prostaglandin F2 alpha (PGF2 alpha), 6-keto-prostaglandin F1 alpha (6KPGF1 alpha), thromboxane B2 (TXB2), leukotriene B4 (LTB4) and 5 hydroxytryptamine (5-HT) before, during and after HPPR. Multiple regression analysis showed that the changes of pulmonary arterial systolic pressure (PASP) and pulmonary arterial diastolic pressure (PADP) correlated well with those of plasma concentration of NE, PGF2 alpha and 6KPGF1 alpha, respectively (r were equal to 0.633 and 0.668, respectively, P < 0.01). The results of orthogonal experiment analysis with an injection of exogenous NE, PGF2 alpha and PGI alpha into main pulmonary artery of dogs showed that NE and the interaction of PGF2 alpha and PGI2 alpha increased PASP (P < 0.05) and PGI2 attenuated PASP (P < 0.01). The interaction of PGF2 alpha and PGI2 and of PGF2 alpha and NE increased PADP(P < 0.01) and PGI2 attenuated PADP (P < 0.01). PMID- 8194383 TI - Antiviral effects on mouse leukemia virus replication by oligodeoxynucleotides in vitro and in vivo. AB - Oligodeoxynucleotides (Oligomers) including modified and unmodified, homo- and heterooligomers were tested for their ability to inhibit mouse SRS leukemia virus (SRSV)-induced proliferation of cells, colony formation, syncytium formation and reverse transcriptase (RT) activity in vitro. Phosphorothioate analogs complementary to Mo-MuLV sequences, as well as noncomplementary homooligomers, were found to be active. Unmodified homooligomer (dC14) also showed inhibition of growth of ascitic lymphoma carrying SRS virus. Our study suggests that different classes of oligonucleotides may inhibit SRSV replication with different mechanisms. PMID- 8194384 TI - Brain alveococcosis. Therapeutic experience in 14 cases. AB - Brain alveococcosis is a rare but threatening disease. In most cases, it metastasized to the brain with late liver or lung alveococcosis. In 14 cases, 8 were secondary, and 6 primary. Nine were treated operatively, 2 medically and 3 proved by autopsy. Eleven cases were monomassive, 2 were multifocal and 1 was extra-cerebral in the cranial base. According to our experiences, extirpation is a radical method, and can improve the cerebral function confirmed by BEAM. Long period use of albendazole showed calcified lesions of CT and disappearance of clinical symptoms. PMID- 8194385 TI - Endocardial mapping and radiofrequency catheter ablation of multiple atrioventricular accessory pathways. AB - Among 174 patients with Wolff-Parkinson-White syndrome, 13 (17.5%) had multiple atrioventricular (AV) accessory pathway. Twenty-one of the 29 pathways were identified by baseline electrophysiologic study and eight were found after the radiofrequency ablation of the initial ones. Bilateral ablation approach was tried in four patients and unilateral approach in nine. Twenty-seven of the pathways (93.1%) were eliminated permanently after a mean of 32 +/- 14 pulses of current delivery. There were no complications. The pulses was more and the procedure took more time (3.6 +/- 0.8 hr) in the group compared to those in single pathway ablation (14 +/- 11 and 2.1 +/- 0.8 hr respectively, P < 0.05). The success rate was identical in the two patient populations (93.1% vs 94.0%, P > 0.05). However, the recurrence in multiple pathway ablation (7.6%) was more than that in single pathway ablation (1.9%, P < 0.01). CONCLUSION: radiofrequency catheter ablation is a safe and effective modality for tachyarrhythmias mediated by multiple accessory pathways. PMID- 8194386 TI - Age-related changes in normal Chinese hearts. AB - The heart weights, ventricular wall thickness and valve circumferences were measured in 507 autopsy specimens of normal hearts from persons aged from 10 to 90 years. The heart weights increased with age and were greater in the males than in the females, except from the 6th to 8th decades where they were reversed. The body weight was the best predictor of heart weight. The ventricular wall thickness in males did not differ significantly from that in females. The values of the indexed left ventricular wall thickness (i.e. values divided by BSA) in the females exceeded those in the males from the 6th to 9th decades. The mean valve circumference was greater in the males but it was significant (P < 0.05) only for the tricuspid valves at the 9th decade of life. The pulmonary valve circumferences were greater than the aortic for all decades and the ratio of the aortic to pulmonary valve circumference remained constant. In the clinical evaluation of the specimens of Chinese hearts, the absence of the aged-related dilatation of the aorta described in Caucasian hearts should be duly taken into account. PMID- 8194387 TI - A Chinese lady with Carney's complex. AB - A young Chinese lady with ACTH-independent Cushing's Syndrome was reported. Her clinical features was compatible with the recently described Carney's complex. Bilateral adrenalectomy was then performed. The diagnosis of bilateral pigmented nodular adrenocortical dysplasia was microscopically confirmed. PMID- 8194388 TI - Anti-idiotypic monoclonal antibodies against anti-ovarian carcinoma monoclonal antibody COC166-9. Generation and application. AB - Anti-idiotypic monoclonal antibody (Mab Ab2) by MAb COC166-9 against ovarian serous papillary adenocarcinoma was prepared. Hybridomas of Ab2 screened by sandwich ELISA and immunocompetitive inhibition tests were procured and named as 6B11 and 1H12. The number of their chromosomes were 93 and 91, and DNA analysis also proved the characteristics of hybridomas. These Ab2s could induce delayed type hypersensitivity (DTH), the cellular immune response. The results of the immune reaction of 6B11 with SKOV3 (ovarian carcinoma cell line) were similar to OC166-9 (Ag), the positive control, while 1H12 was weaker. Anti-anti-idiotypic antibody (Ab3) was also raised by 6B11 and 1H12 respectively. They all showed positive immunohistochemical stainings with ovarian serous adenocarcinoma tissue sections and immunocytochemical stainings with SKOV3 cells as was shown by COC166 9. In the antibody dependent cell mediated cytotoxicity (ADCC) tests, they showed no differences against SKOV3 as compared with COC166-9. We anticipate that 6B11 and 1H12 may be used as vaccines against ovarian carcinoma and may provide a clue for its prevention and treatment. PMID- 8194389 TI - Noncholinergic airway constriction: role of axon reflex and oxygen radicals. AB - In the airways and lungs, activated afferent C-fibers release tachykinins, which induce noncholinergic bronchoconstriction. We have, for several years, focused our research on the role of axon reflex and oxygen radicals in noncholinergic airway constriction in guinea pigs. In this species, the noncholinergic bronchial constriction is not affected by administration of a ganglionic blocking agent, chlorisondamine, indicating that only the afferent C-fiber, not a complete reflex arc, is required for this constriction. Accordingly, we investigated the role of axon reflex by using tetrodotoxin (TTX) and bupivacaine to block impulse conduction in the axon. For the role of oxygen radicals, superoxide dismutase (SOD), catalase (CAT), and dimethylthiourea (DMTU) were employed to scavenge superoxide anion, hydrogen peroxide, and hydroxyl radical, respectively. We used capsaicin, resiniferatoxin (RTX), or hyperventilation to activate afferent C fibers which, in turn, release tachykinins and lead to noncholinergic airway constriction. The constriction was quantified by measuring the maximal expiratory flow rate (Vmax) and dynamic compliance (Crs). Both capsaicin and RTX caused an immediate decrease in Vmax and Crs, indicating severe bronchoconstriction. This constriction decreased gradually with time. Tachykinin depletion abolished neurotoxin-induced airway constriction, suggesting that tachykinins mediate the constriction. Both TTX and bupivacaine significantly attenuated the constriction at 15-20 min after neurotoxin administration. Therefore, these data suggest that the axon reflex plays an important role in noncholinergic bronchial constriction. In other studies, capsaicin- or hyperventilation-induced bronchoconstriction was abolished by tachykinin depletion, as well as significantly ameliorated by the administration of antioxidants. These data indicate that oxygen radicals modulate the tachykinin-mediated noncholinergic airway constriction. PMID- 8194390 TI - Embryonic cerebellar graft development during acute phase of gliosis in the cerebellum of pcd mutant mice. AB - Anatomical and biochemical changes in cerebellum after the onset of pcd gene defects have revealed in addition to Purkinje cell degeneration, the occurrence of secondary degenerative events in granule neurons, neurons of the inferior olivary complex and deep cerebellar nuclei. Transplantation in young mutant animals thereby presents a prospect that not only the missing Purkinje cells may be replaced but the subsequent transneuronal losses may be minimized. The present study has evaluated the outcome of implanting embryonic cerebellar cell suspensions into pcd mutants at the age of 45 day-old, a stage marked by the end of Purkinje cell degeneration. Immunocytochemistry (ICC) was used to monitor the extent of gliosis in host cerebellum and to trace the development of embryonic Purkinje cells grafted. The results suggest that the donor cells have no apparent difficulty in survival during reactive gliosis. Migration of these neuroblasts from the grafted zone into adjacent host molecular layer and significant expression of calcium binding protein (CaBP) by grafted Purkinje cells were noted within 9 days after transplantation. Dendritic patterns of grafted Purkinje cells are well-developed by day 17 post transplantation up to 3 months. In addition, synaptic contacts between host fiber endings and the CaBP-positive dendritic spines are present in the molecular layer of folia containing the graft, suggesting synaptic integration between graft and host. PMID- 8194391 TI - Different central areas involved in the mechanisms of morphine antinociception in the mouse and the rat. AB - The antinociceptive effect of morphine quantitated by the tail-flick (TF) response was studied in mice and rats with various preparations, including: precollicular transection, partial and complete anemic decerebration, vertebral artery infusion, cross-circulation, spinal ligation, spinalization with dura mater intact and spinal subarachnoid infusion. In mice, either precollicular transection or partial anemic decerebration abolished or greatly reduced the morphine antinociceptive action (MAA). However, in rats, neither precollicular transection nor complete anemic decerebration caused any significant reduction in MAA. Studies of vertebral artery infusion and cross-circulation in both species indicated that opiate-sensitive antinociceptive receptors (OSAR) were present in the hindbrain. Although, spinal ligation eliminated MAA in both species, spinalization with dura mater intact only abolished the MAA in rats. On the other hand, studies of spinal subarachnoid infusion showed that only spinal antinociceptive neurons of mice were highly sensitive to the enzyme-resistant enkephalin (Enk) analog. From all these results suggested that both pre- and post collicular structures are necessary for MAA in the mouse, however, in the rat only the post-collicular structures are essential, furthermore, the humoral pathway seems to play a more important role than the neural pathway in the inhibition of the TF response in the mouse but just the opposite in the rat. Therefore, it is concluded that the mechanisms of MAA are different between the mouse and the rat. The possible mechanisms of MAA in both species were discussed. PMID- 8194392 TI - Effects of monoamine precursors on food intake in male rats. AB - Effects of monoamine precursors on food intake in male rats were studied. Rats were subjected to an artificial circadian pattern of eating, i.e., a five-hour feeding program during daytime and food deprived during the rest of day. Feeding responses after treatment of drugs were examined. Intraperitoneal injection of L beta-3, 4-dihydroxyphenylalanine (L-DOPA), DL-threo-dihydroxyphenylserine (DOPS), or 5-hydroxy-L-tryptophan (5-HTP) suppressed food intake. The suppression occurred within the first thirty minutes of the test period and their order of potency came out 5-HTP > L-DOPA = DOPS. The suppressive action of 5-HTP was very strong and lasted at least 3 days. The mechanism of this feeding suppressed action by either the central satiety center or the peripheral inhibiting system was discussed in this context. PMID- 8194393 TI - Involvement of alpha- and beta-adrenoceptors in antinociception at the lumber spinal level in mice. AB - To study the role of the adrenergic receptors in the regulation of nociceptive transmission in male albino mice, the antinociceptive activity of adrenergic drugs was tested with a tail-flick method. Subarachnoid infusion of phenylephrine and clonidine into T13-L1 of spinal cord produced a dose-dependent elevation of the nociceptive threshold in sodium pentobarbital anesthetized mice. The inhibitory effect of alpha-adrenoceptor agonists was antagonized by pretreatment with alpha-adrenoceptor antagonists. Isoproterenol also increased the nociceptive threshold significantly. The antinociceptive effect of isoproterenol was reversed by pretreatment with beta antagonist, propranolol. These findings suggest that spinal adrenergic receptors of both alpha and beta types probably are involved in the inhibition of nociceptive transmission. PMID- 8194394 TI - The effect of mannitol on antidiuretic and natriuretic actions of ADH in rats. AB - The effect of mannitol and glucose on antidiuretic and natriuretic actions of ADH was investigated in water-loaded, male Sprague-Dawley rats anesthetized with sodium pentobarbital (5 mg/100g). Water diuresis was induced and sustained by continuous intravenous perfusion of hypotonic solution containing 0.3% NaCl, 1.67% glucose, 1.2% ethanol and sufficient inulin at a constant rate 150 microliters/min. Arginine vasopressin at a single dose 0.1 ng/100g was tested twice in the phase of water diuresis and in the phase of water diuresis plus mannitol osmotic diuresis. Urine samples were collected at ten-minute intervals. Three doses of mannitol (5.18, 3.63, 1.81 mumol/min/100g) were given into the right renal artery in three groups of experimental rats, respectively. Administration of mannitol did not alter renal inulin clearance but increased urine flow and excretion of sodium from experimental kidney. Our findings show that mannitol reduced antidiuretic response to ADH in the experimental kidney. This reduction was related to intraarterial mannitol doses. Local administration of mannitol increased natriuretic action of ADH in the experimental kidney. However, a small dose (1.81 mumol/min/100g) of mannitol did not increase natriuretic action of ADH. Saline and glucose (5.23 mumol/min/100g) were also infused intra-arterially to replace mannitol. The effect of saline on antidiuretic and natriuretic responses to ADH was found to be insignificant. Glucose reduced antidiuretic response to ADH as mannitol did but failed to alter natriuretic response to ADH as saline did. We conclude that mannitol does positively affect antidiuretic and natriuretic actions of ADH. Glucose has similar effect but much less than mannitol. PMID- 8194395 TI - Progesterone facilitates thrust in female hamsters implanted with estradiol at the medial preoptic area. AB - Progesterone (P) facilitates male-like sexual behavior in female hamsters primed with estrogen. Since estrogen plus P activates lordosis in female hamsters and the site of the hormonal action is at the ventromedial hypothalamus (VMH), it is possible that the same hormones act at the same site to induce male-like sexual behavior. However, VMH lesion abolishes lordosis, but not thrust, in ovariectomized female hamsters treated with estrogen plus P. Therefore, we tried another brain site--the medial preoptic area (mPOA). We implanted cannula, 27 gauge and filled with estradiol at the tip, at the mPOA or the VMH bilaterally in ovariectomized female hamsters. The hamsters received subcutaneous injections of P (0.5 mg in 0.05 ml sesame oil) at noon every fourth day. Behavior tests were conducted the same night of the injection day and the day before. The procedure was repeated five times. During a test night, each experimental female hamster was paired with a male hamster first and then with another estrous female. Recorded behavioral events were duration of lordosis and frequency of thrust. Both mPOA and VMH groups displayed lordosis only on the day of P injection, without any significant group difference. As to the male-like sexual behavior, 9 out of 54 mPOA females displayed thrust at least once but none of 27 VMH females ever did. Furthermore, 7 of the 9 females displayed thrust only on the day of the P injection. We conclude that the mPOA was also the site for the activation of male sex behavior in female hamsters. However, the hormones acting at the mPOA to induce thrusts were estrogen plus P. PMID- 8194396 TI - [Is a demontage of emergency medicine beginning in German rescue service?]. PMID- 8194397 TI - [Surgical specialty distribution in Switzerland and in West Germany and interprofessional interprofessional cooperation]. PMID- 8194398 TI - [Comments on expansion and cost saving potential of ambulatory surgery]. PMID- 8194399 TI - [Classification, diagnosis and differential diagnosis of malignant melanoma]. AB - Due to the recent increase of incidence of malignant melanoma and due to the significance of early detection for a definite cure from the disease, diagnosis and differential diagnosis of malignant melanoma are very important. At first glance the malignant potential of a pigmented mole can be evaluated by the macroscopical ABCD rule (Asymmetry, irregular Border, different Colors, and Diameter larger than 6 mm). In addition, also the history of the patient might be helpful. Thus a malignant melanoma should be considered when a patient reports a new rapidly growing pigmented lesion or a change in an existing mole in color, size, shape, and surface. Itching or burning should also arouse the suspicion of malignant change. Risk factors for the development of a malignant melanmoma are a high number of benign melanocytic nevi, large congenital melanocytic nevi, fair skin types with a tendency to sunburns and a malignant melanoma in the family of the patient. With dermatoscopy, which is skin surface microscopy at 10x magnification, the difficult macroscopical differential diagnosis is facilitated, because this technique opens a new dimension between macroscopy and microscopy. PMID- 8194400 TI - [Stage-dependent surgical resection of malignant melanoma]. PMID- 8194401 TI - [Extremity perfusion in malignant melanoma]. AB - Isolation perfusion was introduced in 1957 by Creech and Krementz for treatment of in-transit metastases from malignant melanoma of the limbs. The isolation of the extremity from the body circulation allows a high concentration of cytostatics without systemic side effects. In combination with hyperthermic tissue temperatures around 41.5 degrees C an additional effect can be expected. Regional metastasizing malignant melanomas with satellites, in-transit or lymph node metastases are generally accepted indications for isolation perfusion. There is still controversy about elective adjuvant perfusion in stage I melanoma. In spite of performing this treatment modality over 40 years in practice there are still many factors under discussion and many problems to be solved. The surgical procedure and techniqual aspects are described in detail. Krementz demonstrated long term survival rates between 19% and 53%. The patients treated in the Surgical Department of the University Hospital in Erlangen since 1975 with satellites and in-transit metastases had a 10-year survival rate of 48%. Considering the historical data of our patients without perfusion with a 10-year survival of 11% there is a highly significant statistical difference. In conclusion isolation perfusion is the therapy of choice in patients with locally metastasized malignant melanoma of the limbs. PMID- 8194402 TI - [Trypsinogen activation peptides in acute pancreatitis. Experimental data and clinical implications]. AB - Trypsinogen activation peptides (TAP) can be found in patients with acute pancreatitis (AP) as well as in different models of experimental AP. First experience has suggested that early elevation of TAP indicates development of necrotizing AP and that the amount of TAP correlates with the extent of acinar cell necrosis and mortality. It is however unknown whether TAP similarly assess severity of AP in the later course of the disease. The present study monitores TAP in plasma, urine and ascites during the initial development of pancreatic injury and correlates the amount of TAP and the extent of pancreatic necrosis over 48 h in a rodent model of AP. While there was no elevation of TAP in control animals or animals with edemantous AP, significant amounts of TAP im plasma were found as early as 30 min following induction of severe necrotizing AP. Serum amylase returned to normal values within 24 h, TAP maintained at high levels until the end of the 48 h observation period. During the first 24 h TAP paralleled the development of acinar cell necrosis, but decreased thereafter despite further progression of pancreatic injury. Our results provide further evidence suggesting that TAP initially precede morphological changes in AP. Early in the course of the disease TAP parallel development of pancreatic injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194403 TI - [The value of quantitative DNA analysis in evaluating the prognosis of differentiated thyroid cancer]. AB - In this study we analyzed DNA ploidy as a potential prognostic parameter in differentiated thyroid carcinoma. In the case of papillary cancer the depth of tumor infiltration, a micro- or macroinvasive tumor growth, an invasion of vessels and the ploidy had an influence on prognosis. In the case of follicular cancer depth of tumor infiltration, the presence of distant metastasis, grading, uni- or multifocal tumor growth and the ploidie had an influence on prognosis. In the case of papillary cancer the multivariate analysis for the ploidy shows a strong and independent influence on the prognosis. Even when comparing with tumor stage, EORTC score and AGES score the ploidy allows an additional prognostic differentiation. In follicular carcinomas a multivariate analysis was not possible due to the strong associations of the prognostic parameters. PMID- 8194404 TI - [Laparoscopic cholecystectomy as standard intervention in symptomatic cholecystolithiasis. Experiences with 1,277 patients]. AB - As a result of 1277 laparoscopic cholecystectomies, which were performed as a standard procedure in uncomplicated and complicated symptomatic cholecystolithiasis, the complication-rates of conventional cholecystectomy and laparoscopic cholecystectomy are compared. It can be demonstrated, that the adoption of the principles of conventional cholecystectomy into laparoscopic technique and a careful preparation can reach the same high level of safety as the so called "gold-standard". PMID- 8194405 TI - [Laparoscopy-assisted reoperation after sigmoid resection and Hartman rectal occlusion]. AB - The anastomosis between the descending colon an the rectal stump after sigma resection and blind closure of the rectum according to Hartmann could be performed as well via an open laparotomy approach as via a laparoscopic procedure. By means of a first group of five laparoscopically reoperated patients the authors are demonstrating the good practicability of their laparoscopic method. Extended adhesions in the pelvic area could be detached in all cases. The advantages of this laparoscopic operation are obvious and in the authors opinion laparoscopic assisted reconnection between colon and rectal stump seems to be a serious alternative to open surgery by laparotomy. PMID- 8194406 TI - [Stenosis of the choledochus by metal clips after laparoscopic cholecystectomy]. AB - A report about a choledochal duct-stenosis caused by metal clips placed during laparoscopic cholecystectomy. Together with this case report literature about bile-duct lesions during laparoscopic surgery is discussed. PMID- 8194407 TI - [Chemical pleurodesis with iodized talcum in persistent therapy refractory bronchocutaneous fistula]. AB - The common therapy of a persistent bronchocutaneous fistula is the operative endoscopic repair of the leak, the parietal pleurectomy or the endoscopic pleurodesis with different agents. Therefore the thoracotomy with all the risks for the patient can be avoid. Complications seen in the thoracoscopic treatment are low and often the result of techniqual problems. However there must be an alternative therapy for patients with a high operational risk. In our case we treated a bronchocutaneous persistent fistula by the instillation of iodized talc effectively. Although talc and others agents are used in the therapy of malignant pleural effusions, the talc poudrage in the therapy of bronchocutaneous fistulas is a good alternative treatment for patients in a bad condition. PMID- 8194408 TI - [Subcutaneous struma recurrence as a sequela of autologous thyreocyte implantation]. AB - Goiter recurrence is a well known fact in the surgical therapy of thyroid diseases. Extremely rare the goiter recurrence is localized in the subcutis or the muscle of the neck. We report on two patients with this type of recurrence. The reason may be an autologous implantation of thyroid follicle cells intraoperatively. It can be avoided by removing all particles of the thyroid gland from the operation area. PMID- 8194409 TI - [Recurrent parotitis in adult]. PMID- 8194410 TI - [3-dimensional finite element stress analysis of the periodontal ligament of bridge abutments in mandibular posterior fixed bridge]. AB - According to the measured data, the characters of all components of fixed bridge and the periodontal supporting tissues, and the dividing principals of finite element, the three-dimensional finite element model was developed on the basis of a try adult mandible. 6 vertical loadings and 1 horizontal loading were applied on the abutments and the pontic. The Emax and Emin of PDL were calculated and the resulting principal stresses were plotted for each loading. PMID- 8194411 TI - [Clinical application of sialography with the time-pressure curve monitored]. AB - Sialography with the time-pressure curve monitored in 66 abnormal parotids was compared with the manual injection technique. The results are: 1. The new procedure makes sialogram image superior, avoids gland parenchymal overfilling, finds the causes of failure promptly, and eliminates the pain and other side effects. 2. Shape of the time-pressure curve and the value of the injection may act as an indicator in differential diagnosis. The curve in Sjogren's syndrome is specific and the injection pressure is obviously higher than that in normal (P < 0.01). In Sialosis the injection pressure is much lower than in normal (P < 0.01). PMID- 8194412 TI - [A study on feasibility of the GR phenolaldehyde resinifying agent]. AB - According to the technological requirements of synthesizing resin and the properties of the resinifying agent, glutaraldehyde, resorcinol and sodium hydroxide with an optimal ratio was selected as a new resinifying agent. The GR resin solidified usually within 20 to 30 minutes, which was suitable to clinical use. Histologic study indicated that GR could resinify living tissues and the residual and infected pulpal tissue in root canals. It not only filled the main canals and sealed the apical foramen, but also infiltrated into the accessory canals and fine branches of canals. The permeating distance of GR in dentinal tubules was short. The results showed GR had the basic properties of resinifying agent. PMID- 8194413 TI - [A study of restoration of seriously damaged posterior teeth by cast metal prostheses]. AB - A total of 38 seriously damaged posterior teeth were restored by cast metal prostheses, including onlays (with pulp chamber retainer and radicular retainer), cast dowelcore, two-piece dowel-core or cast dowel crown. As followed up for 6-48 months, 37 prostheses remained firm and sound, with perfect periphery seal, no secondary caries and pathological changes of peridontium were observed, The clinical consummate rate was 97%, The occlusal force of the restored teeth measured in 14 cases was 13.6-30.2 kg, which can satisfy the needs of masticatory function. The selection of retainers should be in accordance with the position and degree of crown damage of the posterior teeth. The key links guaranteeing smooth insertion and perfect periphery seal of cast metal prostheses were also pointed out. PMID- 8194414 TI - [Clinical application and evaluation of the paper-disk for detecting Candida albicans]. AB - The media and indicators were absorbed in a paper-disk (P-D) which is made of filters of mixed cellulose. When P-D is inoculated and cultured at 37 degrees C, the presence of Candida albicans can be shown by the color change from white to brown within 24 hours. Results showed that P-D was specific to Candida species, and the susceptibility was 380 CFU/ml. Fifty patients suspected of oral candidosis were detected by P-D. Its positive percentage of findings was insignificant compared with that of the conventional cultures (P > 0.05). However, P-D is easy to manipulate and inexpensive, and particularly useful because result can be obtained within 24 hours. PMID- 8194415 TI - [A study of mandibular movement velocity and acceleration in young adults with normal people]. AB - The velocity and acceleration of mandibular movements including the border movement, habitual movement and functional movement were studied in 25 young adults by using D-SGG measuring instrument. The results showed that the conception of functional velocity and the maximum velocity of mandibular movement were developed. The physiological and clinical significance of the value of mandibular movement acceleration can be explained by Newton's Second law, F = ma. The author pointed out that in order to keep the necessary masticatory efficiency, the masticatory velocity enjoy the priority in matching with the masticatory force in mastication. PMID- 8194416 TI - [Peripheral adriamycin injection for therapy of idiopathic trigeminal neuralgia: 42 cases report]. AB - According to the principle that the axoplasm can transmit retrogradely. The author dissected peripheral branch of trigeminal nerve and injected adriamycin into the suffered nerve for treatment of 42 cases with trigeminal neuralgia. All cases were painless within 24h after operation. The effect is positive in the period of 3-18 months follow-up. It is a safe, reliable and uncomplicated treatment way for trigeminal neuralgia. PMID- 8194417 TI - [Study on the salivary adenoid cystic carcinoma with the flow cytometric analysis]. AB - The cellular DNA content of 28 cases of salivary adenoid cystic carcinoma (SACC) were quantified with the flow cytometric analysis. The result showed that majority of SACC (22/28) were diploidy tumors. No significant correlation between the cellular DNA content and the histopathologic appearances, the cellular DNA content and the clinical behavior of SACC was found. PMID- 8194418 TI - [Clinical evaluation of an intraoral fluoride controlled release device]. PMID- 8194419 TI - [Clinical and pathological studies of malignant fibrous histiocytoma (MFH) in the oral and maxillofacial regions with report of 15 cases]. AB - This paper reports 5 patients with MFH in the soft tissues and 10 in the jaws. Fourteen patients (5 in soft tissues and 9 in jaws) underwent surgery, 5 and 3 of the 9 bone cases received additional irradiation and chemotherapy respectively. Fourteen patients had been followed up for 6 months to 4 and 1/2 years. Two patients of jaw had local recurrences 1 to 8 months following surgery; 6 of 9 ones with follow-up died, 2 of whom were associated with pulmonary metastases. MFH of bone showed significantly worse prognosis than those localized in soft tissues, particularly in maxilla. Pathologically, the tumors of this series were divided into 5 types. The relation between the mitosis and the malignancy of MFH in the jaws was significant. Immunohistochemical stains for lysozyme, A, AT and ACT showed that ACT was the most sensitive marker for MFH. PMID- 8194420 TI - [Application and evaluation of bone scanning in the diagnosis and treatment for oral and maxillofacial tumors]. PMID- 8194421 TI - [The study of sialolithiasis and the micro-structure of salivary calculus: clinical analysis of 55 cases]. PMID- 8194422 TI - [A preliminary exploration for bioelectric potential of dental caries]. PMID- 8194423 TI - [Quantitative analysis of AgNOR of mixed tumor of salivary gland]. PMID- 8194424 TI - [Ultrastructural studies of the effect of PGE2 on rabbits' periodontal tissues]. PMID- 8194425 TI - [Effects of medical silicone rubber products]. PMID- 8194426 TI - [Determination of the strength of the mandible and the porous surface of the screw osseointegrated artificial dental implant]. PMID- 8194427 TI - [Relationship between gingival crevicular fluid and serum specific antibody titers in periodontitis and changes after the treatment]. AB - Gingival crevicular fluid (GCF) samples were collected from 80 teeth in 20 periodontitis patients (13 RPP, 7 AP) before and 1 month, 7 months after treatment. Serum samples were taken at the same time. 12 healthy subjects (48 teeth) were chosen as the control group (H). The levels of IgG antibody to Bacteroides gingivalis was measured by ELISA. The relationship between serum and GCF specific antibodies was assessed. Before treatment, the mean ratio of antibody in GCF and serum (the GCF/Sr ratio) in both RPP and AP group was lower than 1, and significantly lower than that in H group. After treatment, the serum antibody titers greatly reduced while GCF antibody increased at 1 month after treatment and decreased at 7 months after treatment. The GCF/Sr ratio raised to greater than 1 in both RPP and AP. The elevation of GCF antibody may be associated with the lower antibody consumption caused by decreasing amount of B. gingivalis in pocket, and/or associated with the local antibody synthesis. It was suggested that the GCF/Sr ratio of antibody level might be used as a significant indicator in evaluation of treatment effectiveness. PMID- 8194429 TI - [RBC Na(+)-Li+ countertransport and Na(+)-K+ cotransport in patients with essential hypertension]. AB - The correlation analyses were performed in 60 patients with essential hypertension (EHT) and 77 normotensives (NT) between RBC Na(+)-Li(+) countertransport (SLC), Na(+)-K+ cotransport (SPT) and blood pressure, Quetelet index (QI), serum insulin, blood lipids, uric acid, blood glucose, etc. Results showed: (1) The SLC in EHT patients were higher, while SPT lower than NT group; (2) The difference between EHT and NT group was much prominent in SLC of male, while prominent in SPT of female; (3) There was no sex difference in SLC and SPT, and the SLC was correlated positively with QI3; (4) By multiple variants stepwise regression analysis, the SLC was shown to be associated positively with systolic and diastolic blood pressure; while the SPT inversely with systolic blood pressure. It suggests that SLC and SPT exert an independent effect on blood pressure. PMID- 8194428 TI - Crystals and arthritis. AB - Monosodium urate, calcium pyrophosphate dihydrate, and basic calcium phosphate (carbonate-substituted hydroxyapatite and octacalcium phosphate) crystal aggregates are associated with gout, pseudogout, and cartilage degeneration (osteoarthritis, Milwaukee Shoulder/Knee Syndrome), respectively. Hyperuricemia is a frequent but nonspecific and inconstant feature of gout just as an elevated synovial fluid inorganic pyrophosphate level is an inconstant feature of pseudogout. Monosodium urate, calcium pyrophosphate dihydrate, or basic calcium phosphate crystals can cause acute inflammation associated with phagocytosis by neutrophilic leukocytes. Each induces neutral protease synthesis and secretion and arachidonic acid metabolism by synoviocytes and macrophages in a dose dependent fashion, postulated to produce the damage to bone, cartilage, and other joint tissues that is perceived clinically as tophaceous destruction or degenerative joint disease. Crystals containing calcium are potent mitogens. All three types of crystals are more common in older persons and will attract additional attention as the mean age of our population increases. Gout is perhaps the most treatable disease in medicine, although mistakes in diagnosis and in choice of appropriate therapy are very common. Acute pseudogout and acute calcific periarthritis are readily treated medically, but the chronic effects of crystals containing calcium are not. New approaches using drugs derived from scientific study of the biologic effects of these crystals may become useful therapeutically. PMID- 8194430 TI - [A study on the changes of myocardial intracellular calcium in patients with heart failure]. AB - Myocardial intracellular calcium was studied in patients with chronic rheumatic valvular disease. Calcium deposit localized by pyroantimonate method was significantly decreased or disappeared on plasmic membrane and was markedly increased in cytoplasma, intramitochondria and I- and A- bands of myofilament in patients with heart failure due to chronic rheumatic heart valvular disease. The degree of intracellular calcium deposit was consistent with the injury of myocardial ultrastructure, suggesting that calcium overload may be one of the major causes of myocardial injury and the angiotensin-converting enzyme inhibitors, beta-adrenergic blockers and calcium channel blockers may be useful for protecting myocardium and improving cardiac function. PMID- 8194431 TI - [A comparative study of the mitochondrial membrane phospholipid localization of lymphocytes from peripheral blood with myocardial cells in patients with chronic heart failure]. AB - Alterations of the membrane integrity of myocardial cells may be involved in the development of heart failure. In the present study, the lymphocytes from peripheral blood were used as a study model from which were observed the cytochemical ultrastructural localization of membrane phospholipids (PL) of mitochondria (Mi) in 28 heart patients with heart failure (HF) and 10 cases without HF history and 9 healthy controls by modified Demer's tricomplex flocculation. The myocardium was sampled during the operation in 20 of them. In HF, an increase consistency with NYHA heart function stages in the number of Mi per individual lymphocyte was observed, while the PL localization of Mi cristae showed different loss. The worse the heart function, higher the ratios of Mi in almost total loss of the localization: 32.6 +/- 8.7% (sx-) in IV, 30.8 +/- 8.8% in III, 10.4 +/- 2.7% in II, 13.6 +/- 3.7% in I vs 6.3 +/- 1.3% in the healthy controls (P < 0.01). The changes were closely parallel to those of the myocardium, 24.6 +/- 4.8% in the class III-IV. 6.9 +/- 1.3% in II, 3.9 +/- 0.5% in I vs 1.7 +/- 0.2% in the controls, P < 0.01, and were related to the dimension of left atrium. It was suggested that the changes have significance in learning the mechanisms of myocardial failure and could be used as an injury indicator of myocardium. PMID- 8194432 TI - [Determination of pulmonary arterial pressure and pulmonary vasoconstrictive responses to hypoxia in healthy Tibetan men]. AB - Elevated pulmonary arterial pressures have been observed in persons after acute or chronic exposure to high altitude. Five normal lifelong male of Tibet descents, 22 +/- 1 years old residents, at the altitudes of over 3658 m were studied in Lhasa (3658 m, 65.3 kPa PB) at rest and during near-maximal exercise. The resting PAM (2 +/- 0.3 kPa, 15 +/- 1 mmHg) and PVR (1.8 +/- 0.2 Wood units) were within sea-level norms and were little changed while breathing a hypoxic gas mixture (PaO2 = 4.80 kPa, 36 +/- 2 mmHg). Near-maximal exercise (87 +/- 13% VO2 max) increased cardiac output more than three-fold to attain values of 18.3 +/- 1.2 L/min but did not elevate PVR. Breathing 100% O2 during near-maximal exercise did not reduce PAM and PVR. We suggested that Tibetan had resting pulmonary arterial pressure that was normal as sea-level standard and exhibited minimal hypoxic pulmonary vasoconstriction both at rest and exercise. These findings are consistent with remarkable cardiac performances and high altitude adaptation in Tibetan. Those with pulmonary arterial hypertension might be a maladaptative response to chronic hypoxia. PMID- 8194433 TI - [Clinical evaluation of simvastatin in the treatment of hyperlipidemia]. AB - Fifty nine cases with hyperlipidemia were divided randomly into two groups. In group I, each patient took simvastatin 10-40mg/day (mean 17.9mg/day). In group 2, each patient took gemfibrozil 1200mg/day. After treatment with simvastatin, in comparing with baseline values, serum level of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) triglyceride (TG), apolipoprotein B (ApoB), and TC/HDL-C (high-density lipoprotein cholesterol) reduced by 34.6% (P < 0.001), 45.4% (P < 0.001), 22.1% (P < 0.01), 21.1% (P < 0.001), and 39.4% (P < 0.001) respectively, and HDL-C, apolipoprotein A-I(Apo A-I) and Apo A-I/Apo B elevated by 14.2%, 21.9% and 64.5% respectively. For lowering TC, LDL-C, Apo B and elevating Apo A-I/Apo B, Simvastatin was better than gemfibrozil (P < 0.01 0.001). However, for lowering TG, gemfibrozil was better than simvastatin (P < 0.001). As for increasing HDL-C and Apo A-I, no significant differences were found between the two groups. No significant side effects were found in all patients but one who developed hypersensitive eruption after gemfibrozil taken, and he was excluded from the trial. PMID- 8194434 TI - [Improvement of prostacyclin-thromboxane A2 balance in patients with acute myocardial infarction by intermittent aspirin]. AB - Forty two patients with acute myocardial infarction (AMI) were randomly distributed to the following groups: (1) the non-aspirin-treated group; (2) the daily-aspirin-treated group (aspirin, 300mg, once everyday); (3) the intermittent aspirin-treated group (aspirin, 300mg, once every three days). In addition to the three groups, a group of normal subjects was selected. Blood was taken by venipuncture of the antecubital vein in patients on the first, second, seventh, fourteenth and twenty-first hospitalized days. The plasma levels of 6-keto prostaglandin F1 alpha(6-keto-PGF1 alpha) and thromboxane B2(TXB2) were measured respectively by the scintillation counting of radioimmunoassay. The ratio of 6 keto-PGF1 alpha to TXB2 (K/T ratio) was also calculated. Conclusions were as follows: (1) Intermittent treatment with low-dose aspirin is superior to daily treatment in improving the PGI2/TXA2 balance in patients with AMI. (2) Daily low dose aspirin has cumulative inhibitory effects on PGI2 and TXA2 synthesis in AMI patients. While intermittent treatment has the same cumulative inhibitory effect on TXA2 synthesis as daily treatment, but no cumulative inhibitory effect on PGI2 synthesis. PMID- 8194435 TI - [A comparative study on the patients with VVI and AAI pacing by equilibrium radionuclide angiography]. AB - Twenty two patients (15 cases of VVI and 7 cases of AAI) were studied before and after implanted pacemaker comparatively with equilibrium radionuclide angiography (ERNA). The results of the phase analysis (PA) and the cardiac function parameters showed that the ventricular excitement conduction-systolic sequence (VEC-SS) of VVI pacemaker group was abnormal, the ventricular systolic coordination (VSC) and the global ventricular systolic function (GVSF) were reduced, while the early ventricular ejection fraction and the diastolic filling velocity were increased after implantation VEC-SS and VSC of AAI group showed no change and the GVSF got improved after implantation. VES-SS of VVI group was abnormal, VSC and GVSF of VVI group were reduced as compared with those of control group, but no changes were found in AAI group after implantation. Hemodynamics appeared to be better in AAI group than that of VVI group, as evidenced by normal VEC-SS and VSC as well as increased GVSE. PMID- 8194436 TI - [The clinical cardiac electrophysiologic effects of tetrandrine]. AB - Acute electrophysiologic effects of intravenous tetrandrine were evaluated with programmed electrical stimulation in 20 patients. The results showed that: (1) tetrandrine significantly lengthened SCL and A-H interval (P < 0.001), AVNERP, AVNWCL and SPERP (P < 0.05). It did not affect the SACT, SNRT, P-A, H-V, Q-T intervals and the ERP of atrium, ventricle and accessory pathway significantly. Its electrophysiologic property is similar to verapamil. (2) It prevented induction of SVT in 4 cases, 4 cases of sustained SVT were no longer sustained, the effective rate is 85.7%. The curative effect on AVNRT (100%) is better than that on AVRT (71.4%). (3) No severe side effect was observed. Therefore, tetrandrine is an effective drug for the treatment of SVT. PMID- 8194437 TI - [The effect of indapamide on cardiac dysfunction in patients with hypertension]. PMID- 8194438 TI - [The changes of zinc and copper in plasma, erythrocytes and lymphocytes in children before and after extracorporeal circulation]. PMID- 8194440 TI - [A study on the changes in systolic and diastolic function during alternative contraction in normal dog's isolated heart]. PMID- 8194439 TI - [Aortic replacement in patients with small aortic root--a modified Manouguian operation with a report in four cases]. AB - Patch enlargement is used for aortic replacement in the cases of small aortic root. Four cases of modified Manouguian operation, a kind of patch enlargement, were presented. In this method, the splitting of aortic leaflet of mitral valve and the opening of left atrial roof were avoided. Combined with a tilting position, a No 21 artificial valve could be implanted. The method is simpler, especially in the cases of double valve replacement, in which there is no possibility to split the aortic leaflet of mitral valve. The author's experiences were introduced. PMID- 8194441 TI - [Pancreatitis in primary hyperparathyroidism (pHPT) is a complication of advanced pHPT]. AB - Pancreatitis occurred in 13 (5.6%) of 234 patients (76 men, 158 women; mean age 63 [2-83] years) who were operated on for primary hyperparathyroidism (pHPT) between 1987 and 1992. The pancreatitis patients had a significantly higher median level of parathormone (340 pg/ml), of serum calcium (3.2 mmol/l) and of thyroid weight (1.7 g) than the remaining 221 patients (135 pg/ml; 2.9 mmol/l; 1.0 g, respectively: P < 0.05 for each). In ten patients pHPT had been diagnosed during an attack of pancreatitis: pancreatitis had been the diagnostic clue to pHPT. After conservative treatment of the pancreatitis and parathyroidectomy seven of the ten patients were free of symptoms during the follow-up. In one patient pancreatitis recurred postoperatively and two patients died of the consequences of haemorrhagic necrotizing pancreatitis. Cholelithiasis, as another possible causative factor for pancreatitis, was present in five of the 13 patients (38%). None of the patients was an alcoholic. These data indicate that there is a positive correlation between advanced pHPT and pancreatitis. Pancreatitis may be the expression of much advanced hyperparathyroidism which has been diagnosed too late. PMID- 8194442 TI - [The regression of an angiocardiographically and electrocardiographically demonstrated anterior-wall aneurysm following percutaneous transluminal angioplasty]. AB - A non-transmural anterior wall infarction due to a subtotal stenosis of the anterior interventricular branch occurred in a 76-year-old man. Angiocardiography 5 weeks later demonstrated an anterior wall infarct with aneurysm. The ECG showed Q waves without any R waves and elevated ST segments in leads V2-V4. Percutaneous transluminal balloon angioplasty (PTCA) of the stenosed artery supplying the infarct area was performed. Two months later the aneurysm was no longer demonstrable by laevocardiography. The ECG changes of the anterior-wall infarct completely regressed over a 5-month period. A second PTCA was later performed because the artery had re-stenosed. The patient has remained free of angina. This case illustrates that even in the presence of ECG signs of a transmural infarct and an angiographically documented ventricular aneurysm indications for recanalization of the infarct vessel by PTCA should be widely set. PMID- 8194443 TI - [The diagnosis and therapy of anal fissures]. PMID- 8194444 TI - [Research strategies in the genetics of high blood pressure]. PMID- 8194445 TI - [The duty of confidentiality with regard to the mass media and the ban on advertising in the treatment of prominent figures]. PMID- 8194446 TI - [Metastases in breast carcinoma]. PMID- 8194447 TI - [The treatment of gonarthrosis]. PMID- 8194448 TI - [Pulmonary hypertension]. PMID- 8194449 TI - [Pulmonary hypertension]. PMID- 8194450 TI - [Thyroid examination before contrast medium administration]. PMID- 8194451 TI - [Error ratio in International Classification of Diseases coding and implementation of the nursing personnel regulation of the Health Organization Law]. AB - Since 1 January, 1993, it has been a legal requirement to enter, for identification of the main diagnosis, the appropriate code from the International Classification of Diseases (ICD) on the documentation forms of the Nursing Personnel Regulation as prescribed under the (German Federal Government's) Health Organization Law. This study was undertaken to analyse the frequency of errors in this coding and the reasons for it. The data of the Nursing Personnel Regulations during the first 6 months of 1993 were compared with the corresponding entries in the diagnostic archives. In 671 of 2308 analysed forms (29%) coding errors were discovered. The rate of errors was especially high in the areas of cardiology (39%), angiology (37%), nephrology (36%) and neurology (35%). However, a high percentage of the wrong codings for cardiological and nephrological diseases were still within the same diagnostic field.--These findings indicate that, to ensure quality, those doctors who do the coding should be fully informed about the potential consequences regarding staffing of such errors. All coding must be done by experienced doctors, be locally checked and, if technically possible, compared with the diagnostic archive entries. Also, the registration of only one main diagnosis is not sensible in the case of patients with multi-organ disease. PMID- 8194452 TI - [Pulmonary aspergillosis in an immunocompetent female patient]. AB - Symptoms of bronchopneumonia developed over 4 months in a 63-year-old woman in previously good health. The symptoms worsened despite treatment with tetracycline (500 mg twice daily for 10 days). Middle-lobe pneumonia was diagnosed both clinically and radiologically, but monotherapy with ofloxacin (200 mg twice daily) was ineffective, as well as combined treatment with gentamycin (80 mg), oxacillin (1 g) and azlocillin (5 g), each three times daily intravenously. Bronchoscopy revealed obstruction of the lumen of the right middle lobe bronchus by viscous purulent secretion which contained a high count of Aspergillus fumigatus, previously found in several sputum samples. The inflammatory process regressed completely within 12 days on itraconazole (200 mg twice daily), combined with nystatin inhalation (100,000 IU five times daily). The only possible aetiologically significant risk factor in this immunocompetent woman could have been her frequent use of a bio-waste container. PMID- 8194453 TI - [Hand and foot purpura ("glove and sock" syndrome) caused by parvovirus B19 infection]. AB - After a period of general nonspecific symptoms (weakness; nocturnal sweating) for a few days a 29-year-old man suddenly developed a purpura-like rash on both hands and feet ("glove and sock") with mild itching and oedema. A blood count demonstrated leukopenia (2100/microliters) with neutropenia (1100/microliters), thrombocytopenia (81,000/microliters) and reticulocytopenia (1/1000), while haemoglobin content was normal. The bone-marrow showed almost complete reduction of erythropoiesis with the presence of giant proerythroblasts. Granulopoiesis and megakaryopoiesis were unremarkable. Positive tests for IgM and IgG antibodies against parvovirus B19 established the diagnosis of infection with this organism. The rash, blood picture and bone-marrow changes all regressed spontaneously, without any treatment, within a week. The petechial or purpuric "glove and sock" syndrome may be a special form of parvovirus B19 infection. PMID- 8194454 TI - [Food allergy. Clinical aspects, diagnosis and therapy from the dermatologic viewpoint]. PMID- 8194455 TI - [Hypersensitive carotid sinus]. PMID- 8194456 TI - [Arm edema after mastectomy]. PMID- 8194457 TI - The nerve of them--beta-cells and nerve growth factor. PMID- 8194458 TI - Growth hormone and prolactin regulate the expression of nerve growth factor receptors in INS-1 cells. AB - We have previously demonstrated that beta-cells express both p75NGF-R and Trk-A, the low and high affinity nerve growth factor (NGF) receptors, respectively. In the current study, we provide evidences that in the beta-cell line INS-1, the expression of these receptors is tightly controlled by GH and PRL, two hormones implicated in beta-cell development and function. Within 24 h of treatment of INS 1 cells with human (h) GH, the numbers of low and high affinity NGF-binding sites, calculated after Scatchard analysis, increase 3- and 2.5-fold, respectively. The increase in the concentration of the high affinity NGF-binding sites is paralleled by an increase in Trk-A protein without any change at the mRNA steady state level, suggesting a translational/posttranslational effect. On the other hand, the increase in low affinity binding sites is paralleled by an increase in the p75NGF-R mRNA steady state level. The effect requires at least 8 h of treatment, and a dose of 50 ng/ml hGH is sufficient to induce an increase in the p75NGF-R mRNA steady state level. The effect of hGH can be mimicked in the same time- and dose-dependent manner by rat PRL and bovine GH, suggesting that the expression of NGF receptors can be transduced by both the somatogenic and lactogenic pathways. Finally, the increase in the p75NGF-R mRNA steady state level after PRL treatment is not due to mRNA stabilization, suggesting a transcriptional control, and requires concurrent protein synthesis. GH and PRL could thus be important regulators of the sensitivity of beta-cells to NGF. PMID- 8194459 TI - Effect of activin on luteinizing hormone-human chorionic gonadotropin receptor messenger ribonucleic acid in granulosa cells. AB - Activin (the dimer of inhibin beta-subunit) is involved in the modulation of granulosa cell function. Recent reports have indicated that activin had an effect on LH/human CG (hCG) receptor induction and steroidogenesis in granulosa cells. To characterize the regulation inducing LH/hCG receptor by activin, we investigated messenger RNA (mRNA) levels, the expression of the LH/hCG receptor, and intracellular cAMP accumulation in cultured rat granulosa cells. Northern blot analysis showed an increase in the LH/hCG receptor mRNA level with FSH (30 ng/ml) and activin (100 ng/ml) cotreatment, whereas activin alone could not augment LH/hCG receptor mRNA at all. After the addition of actinomycin D to the culture medium, LH/hCG receptor mRNA was more stable in the presence of FSH plus activin than in the presence of FSH alone. Similarly, a receptor binding assay revealed that the cotreatment with FSH and activin induced more LH/hCG receptor than FSH alone 96 h after exposure to hormone, but that activin (100 ng/ml) alone could not induce the LH/hCG receptor. Since the primary, if not the sole, second messenger mediating the action of FSH in granulosa cells has been shown to be cAMP, intracellular cAMP accumulation was measured in granulosa cells in the presence of FSH (30 ng/ml) and/or activin (100 ng/ml). Although FSH-stimulated cAMP accumulation reached a peak 15 min after incubation, activin did not significantly alter cAMP accumulation in either control nor FSH-stimulated granulosa cells, indicating that the effects of activin on the LH/hCG receptor in granulosa cells are not mediated by the increase in cAMP. These results demonstrate that activin enhances the FSH-induced LH/hCG receptor mRNA, LH/hCG receptor mRNA stability, and LH/hCG binding sites not due to the stimulation of the adenylate cyclase system. Although the signal pathway from the activin receptor has not been elucidated upon yet, activin is capable of increasing LH/hCG receptor levels through the accumulation of LH/hCG receptor mRNA levels. PMID- 8194460 TI - Sialyltransferase messenger ribonucleic acid increases in thyrotrophs of hypothyroid mice: an in situ hybridization study. AB - Hypothyroid patients and mice have been shown to have circulating TSH that is more highly sialylated than their euthyroid counterparts. To learn about the underlying cellular mechanisms responsible for this increased sialylation of TSH, we used in situ hybridization to examine the beta-galactoside alpha-2,6 sialyltransferase (STase) mRNA content in thyrotrophs and corticotrophs of euthyroid and hypothyroid mice. Mice were treated with or without 0.05% propylthiouracil for 1, 2, 3, 4, or 6 weeks, then pituitaries were removed, and 5 microns slices were immunocytochemically stained for TSH and ACTH. Adjacent sections were used for in situ hybridization. A 48-mer deoxynucleotide probe to rat STase and two control probes were labeled with 35S, and autoradiography was performed. There was an approximately 140% increase in STase mRNA in hypothyroid thyrotrophs compared to euthyroid thyrotrophs by the first week, with a mean increase of 170% in weeks 1-6, whereas corticotrophs exhibited no change in STase mRNA. The increase in hybridization of the STase probe in hypothyroid thyrotrophs may be due to an increased transcription of the STase gene, stabilization of the STase mRNA, or both. Thus, modulation of the STase mRNA levels occurs in thyrotrophs and represents one important mechanism by which the oligosaccharides of TSH are altered under different physiological conditions. PMID- 8194461 TI - Inositol 1,4,5-trisphosphate receptor subtypes in adrenal glomerulosa cells. AB - Expression of the diverse subtypes of inositol 1,4,5-trisphosphate (InsP3) receptor (IP3R) was examined in rat adrenal glomerulosa cells. The polymerase chain reaction products were characterized by means of DNA sequencing and/or restriction enzyme mapping. The predominant subtype expressed is IP3R-1; its alternatively spliced variants containing and lacking segment S1 are present in comparable amounts. The expression level of IP3R-2 is about a quarter that of IP3R-1, whereas IP3R-3 is expressed at a very low level. Sodium depletion, a chronic physiological stimulus of glomerulosa cells, failed to influence the expression of IP3R-1, as measured by competitive polymerase chain reaction, and failed to modify the ratio of the different receptor subtypes, as studied with restriction enzyme mapping. PMID- 8194462 TI - Anorectic effects of estrogen may be mediated by decreased neuropeptide-Y release in the hypothalamic paraventricular nucleus. AB - There is a considerable body of evidence to suggest that estrogen suppresses food intake and body weight gain by an action in the hypothalamus. However, the neurotransmitter/neuromodulator mediating the anorectic effects of estrogen are unknown. Neuropeptide-Y (NPY) is the most potent orexigenic signal known, and NPY producing neurons in the hypothalamus concentrate 17 beta-estradiol (E2). In these studies we tested the hypothesis that estrogen-induced anorectic effects may be due to decreased NPY levels and release in hypothalamic sites previously implicated in the control of food intake. The results show that uninterrupted physiological levels of E2 in ovariectomized rats suppressed daily food intake and body weight gain. Evaluation of NPY concentrations in five hypothalamic sites showed that NPY levels were decreased selectively in the paraventricular nucleus (PVN) and neighboring perifornical nucleus of E2-treated rats. In contrast, concentrations of beta-endorphin, another less potent orexigenic peptide, were not changed by E2 in any hypothalamic site. In the next experiment, the effects of similar E2 treatment on NPY release in vitro from the PVN and ventromedial nucleus were studied in rats killed at the onset of the dark phase when food intake increases in conjunction with increased PVN NPY secretion. The results show that basal and KCl-induced NPY release were significantly decreased from the PVN of E2-treated compared to those in control rats. In contrast, both basal and KCl-induced NPY release from the ventromedial nucleus of E2-treated rats were similar to those in control rats. Collectively, these results show that estrogen suppresses NPY levels and release selectively from the PVN. As NPY levels and release in the PVN have been shown to be highly correlated with appetite status, and the PVN is one of the important sites of NPY action, these findings imply that the anorectic effects of estrogen may be mediated by decreased NPY release from the PVN NPY innervations. PMID- 8194463 TI - The effect of losartan on potassium-stimulated aldosterone secretion in vitro. AB - Potassium (K+) and angiotensin-II (Ang-II) are two distinct secretagogues for aldosterone release. However, a local adrenal renin-angiotensin system is present, and several studies suggest a complex interaction between K+ and locally produced Ang-II. First, superfusing zona glomerulosa (ZG) cells with K+ stimulates the secretion of both Ang-II and aldosterone. Second, K(+)-stimulated aldosterone secretion can be reduced in the presence of angiotensin-converting enzyme inhibitors. Because angiotensin-converting enzyme inhibitors are not specific inhibitors of the adrenal renin-angiotensin system, we further tested the hypothesis that locally produced Ang-II participates in K(+)-stimulated aldosterone release from rat ZG cells by using a specific Ang-II antagonist. Although type 1 (AT1) and type 2 (AT2) Ang-II receptors are present in ZG cells, only AT1 antagonist has been shown to mediate Ang-II-induced aldosterone secretion. Losartan, a specific AT1 antagonist, was used in this study. In the presence of losartan (10 microM for 9 mM K+ and 100 microM for 5 mM K+), the average aldosterone secretion during 2 h of superfusion with 9 mM K+ and 5 mM K+ was 70.1 +/- 5.4% (n = 5) and 58.5 +/- 2.2% (n = 3), respectively, of that in its absence. Losartan did not alter the amount of Ang-II secreted. The inhibitory effect of losartan lasted longer than 60 min after it was terminated. In summary, our results support the hypothesis that locally produced Ang-II contributes to the aldosterone secretory response to K+ stimulation at both physiological and supraphysiological levels. PMID- 8194464 TI - Age-related decrease in neuropeptide-Y gene expression in the arcuate nucleus of the male rat brain is independent of testicular feedback. AB - Neuropeptide-Y (NPY) is thought to modulate reproductive function and food intake. NPY neuronal activity is modulated by sex steroids, and NPY secretion declines with aging. We hypothesized that reduced NPY secretion with aging is due to decreased NPY gene expression, and that this decrease is independent of testicular feedback. To test this hypothesis, arcuate nucleus (ARC) prepro-NPY (ppNPY) mRNA levels, determined by in situ hybridization, and serum testosterone levels, determined by RIA, were compared in sham-operated and orchidectomized young (3 months old), middle-aged (13 months old), and old (23 months old) male Brown Norway (BN) rats. Hybridization area and average optical density (OD) were used as indices of ARC ppNPY mRNA content. In sham-operated rats, both ppNPY mRNA hybridization area and OD decreased progressively with aging, whereas serum testosterone levels were decreased only in old, not in middle-aged or young, rats. In orchidectomized rats, ppNPY mRNA hybridization area also decreased significantly with aging, although OD did not change significantly. The ppNPY mRNA hybridization area was lower in orchidectomized than in intact young and middle-aged rats, whereas OD was unchanged by orchidectomy. Furthermore, the effects of aging and orchidectomy on ppNPY mRNA levels were not localized to a specific region of the ARC. We conclude that in the male BN rat, ARC NPY gene expression is decreased with aging independently of the effects of testicular feedback. This reduction in NPY synthetic capacity may contribute to altered reproductive function and food intake with aging. PMID- 8194465 TI - Recapitulation of the pathway for trophoblast giant cell differentiation in vitro: stage-specific expression of members of the prolactin gene family. AB - The trophoblast giant cell lineage is characterized by endoreduplication and expression of members of the PRL gene family. This report describes the functional consequences following in vitro manipulation of a rat trophoblast cell line, termed Rcho-1. Rcho-1 cells can be cultured under conditions that promote proliferation or differentiation. Proliferation is maintained by culturing the cells in the presence of fetal bovine serum under subconfluent conditions. Differentiation is induced by growing the cells to confluence and removing the mitogenic source. Differentiation is characterized by continued synthesis of DNA in the absence of proliferation (endoreduplication) and the sequential expression of members of the PRL gene family. Western and Northern blot analyses demonstrated that placental lactogen-I (PL-I) was first expressed, followed sequentially by PL-II, PRL-like protein-A, and PRL-like protein-C. The ontogeny of expression of members of the PRL gene family by the Rcho-1 cells recapitulated the pattern of in situ expression by trophoblast giant cells of the junctional zone of the chorioallantoic placenta. A notable difference between in vivo trophoblast giant cell differentiation and in vitro Rcho-1 cell differentiation is the termination of PL-I expression in normal trophoblast giant cells developing in vivo and the continued expression of PL-I in differentiated Rcho-1 cell cultures. The Rcho-1 cell line provides a unique in vitro model for investigating the initiation and maintenance of the trophoblast giant cell differentiation pathway. PMID- 8194466 TI - Receptor dimerization determines the effects of growth hormone in primary rat adipocytes and cultured human IM-9 lymphocytes. AB - Binding of GH to its cell surface receptors is thought to result in the formation of a complex comprised of one molecule of hormone per two molecules of receptor. It has been proposed that this hormone-induced receptor dimerization is important for the mechanism of signal transduction. We have developed a mathematical model for quantitative evaluation of the biological responses associated with sequential receptor dimerization. Based on these predictions, we have investigated whether GH-induced receptor dimerization plays a role in two classical effects of GH, i.e. stimulation of lipogenesis in primary rat adipocytes and GH receptor down-regulation in cultured human IM-9 lymphocytes. Model predictions of biological responses linked to dimer formation yielded a bell-shaped pattern, with self-antagonism at high GH concentrations when monomeric GH-receptor complexes become predominant. The GH lipogenic bioactivity curve was indeed biphasic and first increased in a concentration-dependent manner between 10(-10)-10(-8) M GH (ED50, 0.5 nM), up to a maximum of 1.7-fold stimulation above basal. Then, the response decreased continuously above 5 x 10( 8) M GH, returning to basal levels around 10(-5) M GH. Incubation of IM-9 cells with wild-type human GH resulted in a dose-dependent loss of their surface receptors. In contrast, a human GH analog (G120R), mutated in the second binding surface of the hormone and, therefore, unable to induce GH receptor dimerization, failed to induce receptor down-regulation in the IM-9 cells. Furthermore, when added together with wild-type human GH, human GH(G120R) inhibited, in a concentration-dependent manner, the down-regulation induced by wild-type human GH. Taken together, these data support the hypothesis that receptor dimerization is critical for the stimulation by GH of both lipogenesis in primary rat adipocytes and receptor down-regulation in cultured human IM-9 lymphocytes. PMID- 8194467 TI - Thyroid hormones in tissues from fetal and adult rats. AB - Concentrations of T4 and T3 were recently measured in rat fetal tissues, and the reported values were found to be more than 10-fold higher than those found by us. The differences have been explained by the assumption that previous analytical procedures, neither avoid deiodination during autopsy of the animals or during extraction and purification, because phloretin [(3'),4',4,6 (tetra)trihydroxyaurone], a potent inhibitor of 5'-iodothyronine deiodinase activity in vitro, had not been used to prevent such problems. We here show that perfusion with phloretin during autopsy does not affect 5'-iodothyronine activity or T4 and T3 concentrations in liver, kidney, or brain. Evidence is also provided that the addition of phloretin during the homogenization process is superfluous, as the use of 80% ethanol and 0.02 M NaOH for this step results in undetectable deiodinase activity. Data are presented showing that during the final sample drying, no losses or degradation of T4 and T3 occur, confirming the adequacy of the individual recovery corrections using radiolabeled iodothyronines as internal tracers. We also present quantitative information on the intralaboratory variability of the T4 and T3 concentrations found in tissues from normal fetuses and their mothers as well as in adult males and nonpregnant females. Results are comparable to those obtained by others using entirely different analytical procedures. PMID- 8194468 TI - Cellular and hormonal factors influencing monocyte differentiation to osteoclastic bone-resorbing cells. AB - Osteoclasts are multinucleated cells which form by fusion of circulating mononuclear hemopoietic precursors. The nature of these precursor cells and the roles bone stromal cells and hormonal factors play in their differentiation to osteoclasts are unknown. We cocultured adherent murine blood monocytes (nonspecific esterase and F4/80 positive; tartrate-resistant acid phosphatase negative) with osteoblastic and fibroblastic stromal cell lines in the presence of 2 x 10(-8) M 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Tartrate-resistant acid phosphatase and calcitonin (CT) receptor-positive osteoclastic cells, which formed numerous resorption pits in vitro, were noted after only 4 days in coculture with UMR106 osteoblast-like cells. Resorption was seen in cocultures to which as few as 100 peripheral blood mononuclear cells had been added. 1,25 (OH)2D3 and contact with live bone stromal cells were absolute requirements for monocyte differentiation into bone-resorbing cells. Both salmon CT (5 IU/ml) and prostaglandin E2 (10(-6) M) significantly inhibited bone resorption. Thus, a significant proportion of the peripheral blood mononuclear cells in the monocyte fraction are capable of differentiating into cells showing the cytochemical and functional characteristics of osteoclasts. The presence of specific hormonal [1,25-(OH)2D3] and bone stromal cell elements is necessary for this process to occur; the resultant resorption can be modulated by known inhibitors of bone resorption, CT and prostaglandin E2. PMID- 8194469 TI - Effects of transforming growth factor-beta on parathyroid hormone-related protein production and ribonucleic acid expression by a squamous carcinoma cell line in vitro. AB - The effects of human recombinant transforming growth factor (TGF)-beta 1 were determined on PTH-related protein (PTHrP) production and messenger RNA (mRNA) expression by a canine squamous carcinoma cell line (SCC 2/88) in vitro. TGF-beta increased PTHrP production in a dose- and time-dependent manner (P < 0.05) as measured by RIA, and the effects of TGF-beta treatment persisted up to 72 h after removal. TGF-beta increased PTHrP production by SCC 2/88 cells until cellular confluence, at which time there was no longer a significant increase compared to control. Actinomycin D inhibited the TGF-beta-mediated increase in PTHrP production, suggesting that TGF-beta acted in part by increasing gene transcription. SCC 2/88 cells also produced active TGF-beta as measured by a [3H]thymidine incorporation assay in mink lung epithelial cells. Exposure of SCC 2/88 cells to a neutralizing anti-TGF-beta monoclonal antibody decreased (up to 50%, P < 0.01) basal PTHrP production. TGF-beta increased PTHrP mRNA expression in a dose- and time-dependent manner as evaluated by northern blot analysis. Postconfluent SCC 2/88 cells expressed little mRNA for PTHrP, and there was only a minimal increase in PTHrP mRNA expression in postconfluent TGF-beta-treated cells. These results indicate that TGF-beta increased PTHrP production and mRNA expression in malignant keratinocytes and suggest that TGF-beta may be an important factor in the pathogenesis of humoral hypercalcemia of malignancy. PMID- 8194470 TI - Regulation of interstitial collagenase expression and collagen degradation by retinoic acid in bone cells. AB - In osteoblasts, retinoic acid (RA) modulates the synthesis of various proteins, including collagen. However, little is known about the effects of RA on the regulation of interstitial collagenase synthesis and collagen degradation. After treatment of primary osteoblast-enriched (Ob) cells from fetal rat calvariae with 100 nM all-trans-RA (tRA), collagenase mRNA levels, as determined by Northern blotting, did not change after 2 h, increased by 13- to 18-fold after 6 h, and remained elevated until 48 h. Exposure of Ob cells to 10 nM to 1 microM tRA, 13 cis-RA, and 9-cis-RA induced collagenase mRNA in a dose-dependent manner. Collagenase mRNA induction by RA was blocked by cycloheximide. RA increased the stability of collagenase mRNA in Ob cells, suggesting posttranscriptional regulation. Exposure of Ob cells to RA induced immunoreactive procollagenase in medium, as determined by enzyme-linked immunosorbent assay and Western blotting. RA action on collagen degradation was examined in [3H]proline-pulsed intact calvariae chased with and without tRA for 72 h. The release of [3H]hydroxyproline into culture medium was increased by 64% in the presence of 10 nM to 1 microM tRA. In conclusion, RA increases collagenase synthesis and collagen degradation in bone and is likely to play an important role in bone remodeling. PMID- 8194471 TI - Comparison of the intracellular itineraries of insulin-like growth factor-I and insulin and their receptors in Rat-1 fibroblasts. AB - In this study we have compared the intracellular itineraries of insulin and insulin-like growth factor-I (IGF-I) and their receptors subsequent to ligand internalization in rat fibroblasts. We found that the endocytic rate constant is approximately 3 times as high for insulin as for IGF-I. The dissociation of internalized ligand from its receptor was monitored by the ability of ligand receptor complexes to precipitate in the presence of polyethylene glycol (PEG). Insulin loses its ability to precipitate with PEG more rapidly than IGF-I. After 60 min, less than 10% of the intracellular insulin remains PEG precipitable, whereas 44% of intracellular IGF-I stays PEG precipitable. Ligand degradation was determined by precipitation with trichloroacetic acid (TCA). Insulin degradation after internalization is more rapid compared with IGF-I degradation; after 2 h, 80% of intracellular IGF-I, in contrast to only 30% of intracellular insulin, remains intact. We measured retroendocytosis of insulin and IGF-I by assessing the amount of internalized ligand that was subsequently released from the cells. When analyzing released ligand by TCA precipitation, we found that 25% of insulin and 53% of IGF-I were TCA precipitable. After 120 min, only 16% of insulin and 43% of IGF-I remained intracellular. To provide insight into a possible mechanism that prevents IGF-I from being subjected to the same degree of degradation as insulin, we studied the effect of pH on IGF-I and insulin binding. We found IGF-I binding to be less sensitive to decreases in pH compared with insulin binding. Therefore, it is likely that after internalization, IGF-I does not dissociate from its intracellular receptor as easily as insulin in the acidifying endosome and, therefore, can return to the cell surface via a recycling receptor. In summary, we have observed distinct differences in the intracellular itineraries of IGF-I and insulin and their receptors. IGF-I internalization and degradation proceed less efficiently than insulin internalization, and IGF-I is preferentially targeted into a retroendocytotic pathway in contrast to insulin, which primarily undergoes lysosomal degradation. The differential effect of pH on ligand binding to these structurally related hormone receptors may account for the quantitatively distinct ligand trafficking events. PMID- 8194472 TI - Identification of a major prolactin-regulated protein as 20 alpha-hydroxysteroid dehydrogenase: coordinate regulation of its activity, protein content, and messenger ribonucleic acid expression. AB - We have previously reported that an abundant 37,000 mol wt protein with a pI of 6.15 (37K) is expressed specifically in the corpus luteum and is markedly inhibited by PRL. To identify the 37K, amino acid sequence analysis of the protein was performed. The 37K protein showed sequence similarity with rabbit 20 alpha-hydroxysteroid dehydrogenase (20 alpha HSD), chlordecone reductase, prostaglandin synthase, and 3 alpha-hydroxysteroid dehydrogenase, which are members of the aldo-keto reductase group of enzymes that catalyze the NADPH dependent reduction of carbonyl compounds. Comparison of 20 alpha HSD activity with the level of 37K in the corpus luteum throughout pregnancy demonstrated a close correlation between enzyme activity and luteal levels of the protein. Both protein and enzyme activity were low early in pregnancy, reached a nadir between days 5-19, and reappeared abruptly between days 19-21 of pregnancy. To establish that the enzyme activity is intrinsic to the 37K, the protein was purified from sodium dodecyl sulfate-polyacrylamide electrophoresis gels (SDS-PAGE), renatured, and assayed for 20 alpha HSD activity. The renatured protein exhibited substantial 20 alpha HSD activity. As 20 alpha HSD is known to play a major role in the termination of pregnancy in the rat, it was of interest to examine whether the rapid appearance of the 37 K protein at the end of pregnancy is accompanied by the induction of 20 alpha HSD gene expression. Northern blot analysis using a rabbit cDNA for 20 alpha HSD indicated that the pattern of 20 alpha HSD mRNA expression in the corpus luteum closely paralleled the ontogeny of 20 alpha HSD enzyme activity as well as 37K protein levels. Our studies demonstrated that 20 alpha HSD protein and mRNA levels are coordinately regulated, and that the profound inhibitory effect of PRL on 20 alpha HSD activity is apparently due to inhibition of 20 alpha HSD gene expression, leading to the disappearance of the protein from the corpus luteum. PMID- 8194473 TI - Regulation of type 1 angiotensin II receptor messenger ribonucleic acid expression in human adrenocortical carcinoma H295 cells. AB - We have studied the hormonal regulation of type 1 angiotensin-II receptor (AT1-R) mRNA expression and [125I]angiotensin-II ([125I]AII) binding in human adrenocortical carcinoma H295 cells, which exhibit predominantly AT1-subtype receptors. Activation of the cAMP signaling pathway with forskolin or (Bu)2cAMP caused a rapid decrease in AT1-R mRNA levels (decreased 65% within 3 h). This preceded a time-dependent (maximal, 70% within 12 h) and dose-dependent (IC50, 2 microM forskolin) loss of [125I]AII binding together with decreased phosphoinositidase-C activation (72% decrease) on subsequent AII challenge. Thus, the decreases in AT1-R mRNA levels and functional receptor expression parallel each other in response to activation of protein kinase-A. AII treatment also caused a rapid loss in AT1-R mRNA (maximal, 80% decrease within 3 h), but 48-h treatment caused both [125I]AII binding and the subsequent phosphoinositidase-C response to decrease by only 6% (P < 0.05) and 22% (P < 0.05), respectively. The effect of AII on AT1-R mRNA levels was fully reproduced by the combination of calcium ionophore (A23187) and phorbol ester (12-O-tetradecanoylphorbol 13 acetate), suggesting that AII action was through protein kinase-C and possibly other Ca(2+)-sensitive protein kinases. The effect of AII, but not forskolin, was reversed by treatment in the presence of cycloheximide. In conclusion, control of AT1-R expression is differentially regulated by adenylate cyclase and phosphoinositidase-C signaling pathways, which act at multiple levels in human adrenocortical cells. PMID- 8194474 TI - Basic fibroblast growth factor receptor in the rat adrenal cortex: effects of suramin and unilateral adrenalectomy on receptor numbers. AB - Previous studies have suggested that basic fibroblast growth factor (bFGF) is involved in the mediation of the compensatory adrenal growth response. These studies were undertaken to identify the bFGF receptor in the rat adrenal cortex and determine bFGF receptor levels in vivo. Initial studies using primary cultures of rat glomerulosa cells demonstrated a high affinity binding site with a Kd of 10 pM, consistent with reported values for the bFGF receptor; however, these results could not be demonstrated in capsule-glomerulosa tissue. Using autoradiography to verify the existence of bFGF receptors in vivo, heparin insensitive [125I]bFGF-binding sites were concentrated primarily in the capsule and glomerulosa of the adrenal cortex, suggesting the presence of FGF receptors. The presence of bFGF receptors was further verified by demonstration of internalization of [125I]bFGF into cells of capsule-glomerulosa preps. This approach was used to demonstrate that suramin (a bFGF antagonist) pretreatment of rats results in bFGF receptor up-regulation in the adrenal cortex. In addition, we demonstrated a decrease in bFGF internalization in the remaining adrenal 24 h after unilateral adrenalectomy, suggesting the utilization of bFGF during the compensatory adrenal growth response. Together, these data support a role for bFGF in autocrine stimulation of the adrenal cortex and in the compensatory adrenal growth response. PMID- 8194475 TI - Uptake of thyroxine in cultured anterior pituitary cells of euthyroid rats. AB - The uptake of [125I]T4 was investigated in cultured anterior pituitary cells isolated from adult fed Wistar rats and cultured for 3 days in medium containing 10% fetal calf serum. Experiments were performed with [125I]T4 (10(5) to 2 x 10(6) cpm; 0.35-7 nM) in medium containing 0.5% or 0.1% BSA. The uptake of [125I]T4 increased with time and showed equilibrium after around 1 h of incubation. The presence of 10 microM unlabeled T4 during incubation decreased the uptake of [125I]T4 by 65-70% at all time intervals. After 24 h of incubation, 1.5% iodide and 3.2% conjugates were detected in the medium, whereas around 20% of cellular radioactivity represented [125I]T3. The 15-min uptake of [125I]T4 was significantly reduced by simultaneous incubation with 100 nM T4 (by 24%; P < 0.05), 100 nM T3 (by 38%; P < 0.001), or 10 microM rT3 (by 32%; P < 0.001), whereas 10 microM tetraiodothyroacetic acid (Tetrac) had no effect. Furthermore, preincubation (30 min) and incubation (15 min) with 10 microM monodansylcadaverine, oligomycin, or monensin reduced the uptake of [125I]T4 by 30%, 50%, and 40%, respectively (all P < 0.001). Substitution of Na+ in the buffer by K+ diminished the uptake of [125I]T4 by 39% (P < 0.005); 2 mM phenylalanine, tyrosine, or tryptophan reduced [125I]T4 uptake by 18% (P < 0.05), 18% (P = NS), and 33% (P < 0.005), respectively. Our data suggest that the pituitary contains a specific carrier-mediated energy-requiring mechanism for [125I]T4 uptake that is partly dependent on the Na+ gradient. In addition, part of [125I]T4 uptake in the pituitary might occur through an amino acid transport system. When expressed per pM of free hormone, the 15-min uptake of [125I]T4 was approximately as high as that of [125I]T3. Because the reduction of [125I]T4 uptake by T4, T3, monodansylcadaverine, oligomycin, and monensin was roughly the same as the previously reported reduction of [125I]T3 uptake by the same compounds, it is further suggested that T4 and T3 share a common carrier in cultured anterior pituitary cells. PMID- 8194476 TI - Brain natriuretic peptide in plasma, atria, and ventricles of vasopressin- and phenylephrine-infused conscious rats. AB - To evaluate the mechanisms of brain natriuretic peptide (BNP) gene expression, we determined the effect of acute cardiac overload (from 30 min to 4 h) on atrial and ventricular BNP mRNA levels in normal and hypertrophied myocardium. Arginine8 vasopressin (AVP; 0.05 microgram/kg.min) and l-phenylephrine (PHE; 20 micrograms/kg.min) were infused iv to increase cardiac workload in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. At the age of 10-22 months, during the established phase of ventricular hypertrophy, baseline BNP synthesis was increased in the hypertrophic ventricular cells of SHR, as reflected by about 2-fold (P < 0.05-0.001) elevation of levels of immunoreactive BNP (IR-BNP) and BNP mRNA. Intravenous infusions of AVP and PHE increased mean arterial pressure, plasma IR-BNP levels, and ventricular BNP mRNA levels within 1 h of pressure overload; peak levels of BNP mRNA were reached at 4 h. The increase in BNP mRNA levels was slightly greater in the epicardial (2.0- to 2.6-fold; P < 0.01) than in the endocardial layer (1.9- to 2.0-fold; P < 0.01) of the left ventricle. The rapid stimulation of ventricular BNP mRNA synthesis induced by AVP and PHE was accompanied by the simultaneous activation of left atrial BNP gene expression. Left atrial BNP mRNA levels were increased significantly in response to 1-h infusions, and values peaked in both the AVP- and PHE-infused SHR at 2 h, i.e. a 3.6-fold increase in BNP mRNA levels in left atria in AVP-infused SHR, and a 2.5-fold increase in PHE-infused SHR. Right atrial BNP mRNA levels remained unchanged during drug infusion, except for a transient increase in the WKY after 30 min of infusion. The induction of BNP synthesis was also reflected by increased ventricular IR-BNP levels, whereas AVP and PHE did not affect atrial IR BNP concentrations or contents. In conclusion, the present study shows that pressure overload rapidly stimulates BNP gene expression in the hearts of normal and hypertensive rats. Thus, locally generated BNP in the heart muscle may play a significant role in cardiac adaptation to acute changes in mechanical load. PMID- 8194477 TI - Modulation of the expression of murine lupus by gonadotropin-releasing hormone analogs. AB - Recent studies have suggested that hypothalamic and pituitary hormones may directly influence the immune system. One such hormone with immunomodulatory properties is GnRH. We hypothesized that GnRH and/or the gonadotropins might alter the severity of autoimmune disease through mechanisms distinct from their effects on gonadal hormones. This possibility was tested in a murine model of lupus. We assessed disease severity over time in intact and castrated, male and female, lupus-prone (SWR x NZB) F1 hybrid mice during treatment with GnRH agonist, GnRH antagonist, or vehicle. Compared to vehicle administration, GnRH antagonist administration significantly decreased total serum immunoglobulin G and anti-DNA antibodies in castrated male and female mice and significantly improved survival. In contrast, GnRH agonist administration exerted reciprocal effects in castrated mice, leading to early increases in serum anti-DNA and total immunoglobulin G levels. We conclude that GnRH and/or the gonadotropins can modify the expression of murine lupus independently of their regulation of gonadal steroid secretion. PMID- 8194478 TI - Inhibition of 1,25-dihydroxyvitamin D3 stimulated osteocalcin gene transcription by tumor necrosis factor-alpha: structural determinants within the vitamin D response element. AB - Control of osteoblast function requires the coordinate activity of systemic and local regulatory factors. We have investigated the mechanism of interaction between the secosteroid 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and the cytokine tumor necrosis factor-alpha (TNF-alpha) by measuring their effects on two 1,25 (OH)2D3 responsive matrix protein genes, osteocalcin (OC) and osteopontin (OP). Our previous studies revealed that an inhibitory effect of TNF-alpha on 1,25 (OH)2D3-stimulated OC gene transcription is conferred by the same 25 base pair region of 5'-flanking DNA that confers a response to vitamin D (VDRE). Gel mobility shift studies of [32P]VDRE binding to ROS 17/2.8 cell nuclear extract revealed that TNF-alpha inhibits 1,25-(OH)2D3 stimulated formation of specific retinoid X receptor/vitamin D receptor (RXR/VDR)-DNA complexes in vitro. To determine if TNF-alpha was inhibiting nuclear protein-VDRE binding by modulation of VDR availability, we measured intranuclear VDR in cells treated with 1,25 (OH)2D3 (10(-8) M), TNF-alpha (100 ng/ml), or both, by western blot. 1,25-(OH)2D3 caused upregulation of the nuclear VDR. Treatment with TNF-alpha inhibited the 1,25-(OH)2D3-stimulated up-regulation of VDR nuclear protein content. However, down-regulation of VDR was unlikely to be the mechanism of TNF-alpha action because TNF-alpha had no effect on 1,25-(OH)2D3 stimulation of steady state OP messenger RNA or transcription of an OP-VDRE-chloramphenicol acetyl transferase reporter construct. These results suggest that decreased VDR alone does not explain the mechanism of TNF-alpha action. VDRE structural requirements for TNF alpha action were characterized by comparing binding of mutant and hybrid forms of mouse (m)OP-, rat (r)OC-, and human (h)OC-VDRE probes to nuclear protein from cells treated with 1,25-(OH)2D3 and/or TNF-alpha. These homologous vitamin D response elements differ in that an AP-1 sequence is included in the rOC-VDRE and hOC-VDRE but not in the OP-VDRE. Gel mobility shift analysis revealed that TNF alpha inhibited 1,25-(OH)2D3 stimulation of nuclear protein binding to rOC-VDRE and hOC-VDRE to 59% and 69% of control, respectively, but had no effect on 1,25 (OH)2D3 stimulation of nuclear protein binding to OP-VDRE. The effect of TNF alpha could not be conferred in a mutant OP-VDRE in which the rOC-VDRE AP-1 sequence was inserted.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8194479 TI - Two glucose-signaling pathways in S14 gene transcription in primary hepatocytes: a common role of protein phosphorylation. AB - Transcription of the rat S14 gene is induced in response to increased carbohydrate metabolism in the liver. Because carbohydrate-induced changes in lipogenesis are mediated in part by changes in phosphorylation of multiple proteins, we investigated the role of protein phosphorylation on transcriptional regulation of the two carbohydrate response elements, a thyroid hormone receptor independent carbohydrate response element and a thyroid receptor-dependent glucose response element located up-stream of the S14 gene. S14 reporter constructs were transiently transfected into rat primary hepatocytes and incubated with the protein or phosphatase inhibitor okadaic acid calyculin-A, or one of several protein kinase activators. Low dose okadaic acid blocked glucose induction from both elements without inhibiting glucose metabolism. Calyculin-A, a preferential phosphatase-1 inhibitor, only blocked the glucose response when glucose metabolism was inhibited. The protein kinase-C activator, 12-myristate 13 acetate, did not change the glucose responses, whereas the protein kinase-A activator, 8-(4-chlorophenylthio)cAMP, inhibited S14 transcription by inhibiting glucose metabolism. In contrast, the calcium ionophore A23187, a calmodulin kinase activator, mimicked the effect of low dose okadaic acid, but had no effect on glucose metabolism. We conclude that protein phosphatase-2A and calmodulin kinases may be involved in the glucose signaling pathway of the S14 gene. A similar phosphorylation step may be involved in the two distinct glucose response pathways. PMID- 8194480 TI - Platelet-derived growth factor-AA and -BB (PDGF-AA and -BB) enhance the synthesis of PDGF-AA in bone cell cultures. AB - Platelet-derived growth factor (PDGF), an agent with important mitogenic effects for bone cells, exists in three isoforms, PDGF-AA, -BB, and -AB. PDGF-AB and -BB are the prevalent circulating isoforms, whereas normal unstimulated cells of the osteoblast lineage synthesize primarily PDGF-AA. We examined the effects of PDGF BB on PDGF-A mRNA expression and PDGF-AA polypeptide concentrations in cultures of osteoblast-enriched cells from 22-day-old fetal rat calvariae (Ob cells). In a selected number of experiments we compared the effects of PDGF-BB with those of PDGF-AA on PDGF-A mRNA levels. Steady state PDGF-A mRNA levels were determined by Northern blot analysis, and PDGF-AA concentrations were determined in acidified and fractionated culture medium by a specific RIA for PDGF-A chains. Treatment of Ob cells with PDGF-AA or -BB at 0.3-3.3 nM caused a dose-dependent increase in steady state PDGF-A mRNA, an effect that was initially observed after 2 h. Treatment with PDGF-BB at 1-3.3 nM for 24 h increased PDGF-AA polypeptide concentrations by 2- to 5-fold. The effects of PDGF on PDGF-A mRNA and polypeptide levels were prevented by the protein synthesis inhibitor cycloheximide at 3.6 microM. Phorbol 12-myristate 13-acetate at 1 microM increased PDGF-A mRNA after 2-6 h and PDGF-AA polypeptide levels after 24 h by 2 fold. However, the protein kinase-C inhibitor staurosporine at 50 nM did not modify basal PDGF-A mRNA levels and did not prevent the stimulatory effect of PDGF-AA or -BB on PDGF-A mRNA or PDGF-AA polypeptide levels. In conclusion, PDGF BB and -AA increase skeletal PDGF-A synthesis, an effect that reveals autoinduction of PDGF in bone cells. PMID- 8194481 TI - Differential expression of corticotropin-releasing hormone in developing mouse embryos and adult brain. AB - CRH mRNA was detected by in situ hybridization histochemistry in numerous regions of the adult mouse brain, including most prominently the paraventricular nucleus (PVN) of the hypothalamus, the inferior olivary nucleus, and Barrington's nucleus. After adrenalectomy, steady state CRH mRNA levels increased 1.7-fold, specifically in the PVN, consistent with reports of negative glucocorticoid regulation of CRH expression in the rat PVN. Ontogenetic analysis of CRH expression in fetal and neonatal mouse brain demonstrated CRH mRNA in PVN, Barrington's nucleus, olivary complex, and amygdaloid primordia on embryonic day 13.5. In contrast, CRH mRNA was not detectable in the cortex until after birth. CRH expression also exhibited differential regulation in ontogeny. CRH mRNA reached adult levels at markedly different times of development in each brain region, and CRH expression was reduced specifically in the PVN just before birth and the stress hyporesponsive period. High levels of CRH mRNA were present transiently in the developing lung and celiac ganglion. The novel findings of CRH expression in fetal lung during the period of glucocorticoid-induced lung maturation and in celiac ganglion during development of the sympathetic nervous system indicate that CRH may have some important developmental functions in addition to its role in activation of the stress response. PMID- 8194482 TI - Uterine oxytocin gene expression. I. Induction during pseudopregnancy and the estrous cycle. AB - We have recently demonstrated that the gene encoding the hypothalamic peptide oxytocin (OT) is highly expressed in the rat endometrial epithelium during the last 4 days of pregnancy. Here, we show that uterine OT gene expression is also induced during the proestrous phase of the estrous cycle and after induction of pseudopregnancy. In mature female rats, OT mRNA levels increased more than 10 fold between diestrus and proestrus and remained elevated at estrus. The levels attained at estrus corresponded to about 1/20th of the levels present at term. In immature rats rendered pseudopregnant by treatment with pregnant mare serum and hCG, uterine OT mRNA levels rose steadily and reached a maximum on day 14 of pseudopregnancy, corresponding to about 1/8th of the levels observed on day 21 of normal pregnancy. Oil-induced decidualization of the left uterine horn prolonged pseudopregnancy and maintained OT mRNA levels in both uterine horns until day 19 of pseudopregnancy. These changes were tissue specific, as hypothalamic OT mRNA levels remained essentially unaffected. The present findings demonstrate that either spontaneous or induced changes in endogenous steroid levels are capable of eliciting important changes in uterine, but not hypothalamic, OT gene expression. PMID- 8194483 TI - Uterine oxytocin gene expression. II. Induction by exogenous steroid administration. AB - As we have recently shown, the gene encoding the hypothalamic nonapeptide oxytocin (OT) is expressed in the rat endometrial epithelium during late pregnancy and the estrous phase of the estrous cycle. To investigate the role of ovarian steroids in the regulation of uterine OT gene expression, Silastic capsules containing estradiol or progesterone were implanted into immature ovariectomized rats. Exposure to estradiol alone for 2 days caused a significant rise in OT mRNA. Administration of progesterone alone was without effect. However, a strong synergism was observed when the two hormones were applied together; progesterone potentiated the effect of estradiol by a factor of 7. In animals treated with steroids for 4 days, the removal of either the estradiol or progesterone capsule after day 2 led to a decrease in the total amount of OT mRNA accumulation, implying that the continued action of both steroids was required to achieve maximal OT mRNA levels. Immunocytochemical analysis demonstrated that the main site of steroid-induced uterine OT gene expression is the endometrial epithelium, the same site where endogenously induced OT gene expression occurs at the end of pregnancy. The OT mRNA levels achieved after 4 days of treatment with both steroids were comparable to those achieved at estrus or during pseudopregnancy, but corresponded to less than 20% of the levels present in the uterus on day 21 of pregnancy. These data suggest that in the uterus, the synergistic action of ovarian steroids represents an important, but probably not exclusive, regulator of OT gene expression. PMID- 8194484 TI - Regulated production and intracrine action of 1,25-dihydroxyvitamin D3 in the chick myelomonocytic cell line HD-11. AB - To better understand the extrarenal production of active vitamin D metabolites by cells of the monocyte/macrophage lineage, we investigated the 25-hydroxyvitamin D (25OHD)-1-hydroxylation reaction in the v-myc-transformed chick myelomonocytic cell line HD-11; the 1-hydroxylation reaction in this cell line has a high affinity for 25-hydroxylated vitamin D substrates, is localized to mitochondria, and is associated with cytochrome P450 activity. In this study we demonstrated that the HD-11 cell 1-hydroxylation reaction in vitro is not affected by the majority of extracellular regulatory factors that modulate expression of the renal 25OHD-1-hydroxylase in vivo. A 50% increase in extracellular calcium and phosphate concentrations, physiological inhibitory events for renal 1,25 dihydroxyvitamin D [1,25-(OH)2D] synthesis, did not decrease basal expression of the HD-11 cell 1-hydroxylation reaction, nor did a 50% decrease in extracellular calcium and phosphate concentrations, stimulatory signals for the 1-hydroxylase in vivo, increase 1,25-(OH)2D3 synthesis in vitro. Receptor-saturating concentrations of PTH and PTH-related peptide were similarly without effect. In contrast, the HD-11 1-hydroxylation reaction was significantly stimulated in a dose-dependent fashion by the macrophage stimulatory agents lipopolysaccharide [P < 0.001 at a maximum effective concentration (EC100) of 25 micrograms/ml] and interferon-gamma (P < 0.001 at EC100 of 1000 IU/ml) and by insulin-like growth factor-I (P < 0.01 at EC100 of 15 nM) with the rank order of stimulation being interferon-gamma > lipopolysaccharide > insulin-like growth factor-I. Dexamethasone (> or = 10 nM) and the cytochrome P450 inhibitors (EC100, 20 microM), ketoconazole, clotrimazole, and menadione, all significantly inhibited the HD-11 cell 1-hydroxylation reaction. The naphthoquinone menadione, which blocks electron transfer to the P450-associated enzyme, was the most effective inhibitor of the reaction in both intact cells (3 +/- 1% of basal expression; P < or = 0.002) and after reconstitution of HD-11 cell mitochondrial extracts with a ferredoxin, reductase, O2, and NADPH (5 +/- 1% of basal; P < or = 0.02). We have also shown that 1,25-(OH)2D3 produced from substrate 25OHD3 appears to exert an endogenous (intracrine) inhibitory effect on HD-11 cell growth; incubation of HD 11 cells with a concentration of ketoconazole (10 microM) known to reduce 1,25 (OH)2D3 production by roughly 50% restored 50% of the growth deficit induced by 1,25-(OH)2D3 (EC100, 100 nM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8194485 TI - Tumor necrosis factor increases the rate of lipolysis in primary cultures of adipocytes without altering levels of hormone-sensitive lipase. AB - To investigate the effects of cytokines on adipocyte lipolysis, a macrophage cell line (RAW 264.7) was treated with Escherichia coli lipopolysaccharide (1 microgram/ml) for 18 h to induce cytokine release. Conditioned medium (5%, vol/vol) from these cells was added to rat epididymal adipocytes isolated and incubated under sterile conditions. After incubation, the adipocytes were washed, and the rate of lipolysis (glycerol release) was determined after a further 1-h incubation. The conditioned medium caused an approximately 2.7-fold increase in lipolysis, detectable after 6-12 h, maximal by 24 h, and reversible by 48 h after washing the cells. The effect of conditioned medium was reversed by a neutralizing antibody to mouse tumor necrosis factor-alpha (TNF alpha), and the direct addition of recombinant human TNF alpha (0.1-50 ng/ml) reproduced the effect, with a half-maximally effective concentration of approximately 3 ng/ml. The effect of TNF on the expression of hormone-sensitive lipase (HSL; the rate limiting enzyme for lipolysis) was investigated by Western immunoblots using an antibody raised to a bacterially expressed 96-amino acid portion of the HSL enzyme. TNF treatment did not alter the concentration of immunoreactive HSL. From these data we conclude that 1) macrophages release a cytokine(s) in response to lipopolysaccharide that stimulates lipolysis in freshly isolated adipocytes; 2) TNF alpha can account for most, or perhaps all, of this effect; 3) TNF alpha increases the rate of lipolysis by a mechanism that does not involve increased expression of HSL. Based on the time-dependent aspects of TNF alpha stimulation and the lack of change in immunoreactive HSL, the findings suggest a TNF-induced posttranslational modification of the enzyme. PMID- 8194486 TI - Differential regulation of astrocyte plasminogen activators by insulin-like growth factor-I and epidermal growth factor. AB - Rat astrocytes synthesize and secrete two types of plasminogen activators (PAs), tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), whose functions are related to cell proliferation, migration, and differentiation during development. The regulation of PAs produced by brain astrocytes is poorly understood. In a previous report we demonstrated that t-PA and u-PA are each independently regulated by cAMP-dependent protein kinase and protein kinase-C. In the present study we examined the effects of three well characterized astrocyte mitogens, insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF), on the PA activities produced and secreted by rat astrocytes in vitro. We found that IGF-I and EGF increase cell-associated total PA activity in astrocyte-conditioned medium (CM). The effects of both growth factors were dose and time dependent, and maximal stimulation was achieved after 72 h of treatment with the highest dose tested (100 nM). IGF-I stimulated the cell-associated PA activity more than the CM activity, whereas EGF showed an opposite pattern, suggesting that the secretion of PA is differentially modulated by IGF-I and EGF. PDGF had no effect on astrocyte PA activities at any dose or time point included in the study. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis/zymography showed type specific changes in CM and cell-associated PA activity after growth factor treatment. IGF-I stimulated only t-PA, whereas EGF induced a marked increase in u PA activity and a more limited increase in t-PA. PDGF did not modify either t-PA or u-PA activity. In summary, our results show that IGF-I and EGF each had different effects on PA activities, whereas PDGF had no effect. This diversity in the patterns of growth factor regulation of PAs suggests that the production of astrocyte PAs is not simply related to mitogenesis. More likely, astrocyte PAs are involved in a wide range of growth factor-mediated actions in the developing brain. PMID- 8194487 TI - Distribution of androgen receptor immunoreactivity in vasopressin- and oxytocin immunoreactive neurons in the male rat brain. AB - Arginine vasopressin-immunoreactive (AVP-ir) neurons in the bed nucleus of stria terminalis (BST) and medial amygdaloid nucleus are very responsive to gonadal hormones. After gonadectomy, these neurons lose their AVP immunoreactivity and stop expressing AVP mRNA. Testosterone treatment reverses these changes, acting via androgen as well as estrogen receptor-mediated mechanisms. Although AVP-ir neurons contain estrogen receptor immunoreactivity, it is not known whether they also contain androgen receptor immunoreactivity. To answer this question, brains of male rats were stained immunocytochemically for AVP as well as for androgen receptors. In the BST and medial amygdaloid nucleus, respectively, 90.5% and 91.2% of the AVP-ir neurons contained androgen receptor immunoreactivity. In contrast, in the suprachiasmatic nucleus, the supraoptic nucleus, and the magnocellular portion of the paraventricular nucleus (PVN), none of the AVP-ir neurons contained androgen receptor immunoreactivity. In the ventral zone of the medial parvocellular part of the PVN (mpvPVN), 4.3% of the scattered AVP-ir neurons contained androgen receptor immunoreactivity. One of the control experiments, i.e. staining sections for oxytocin (OT) rather than AVP, revealed that although OT-ir neurons in the supraoptic and magnocellular portion of the PVN did not contain androgen receptor immunoreactivity, 52.5% of the OT-ir neurons in the mpvPVN did. The results suggest that androgens can bind to androgen receptors in AVP-ir neurons in the BST and medial amygdaloid nucleus, possibly to influence AVP expression. The results also suggest that androgens can bind to androgen receptors in AVP-ir and OT-ir neurons in the mpvPVN. The function of the latter interaction, however, is unclear. PMID- 8194488 TI - Regulation of insulin-like growth factor-II gene expression in the ovine fetal adrenal gland by adrenocorticotropic hormone and cortisol. AB - Maturation and activation of the fetal adrenal gland is crucial to fetal organ maturation and the onset of parturition in sheep. Insulin-like growth factors (IGFs) have been demonstrated to promote fetal adrenal mitogenesis and steroidogenesis in some species. Our previous studies showed that IGF-II mRNA is expressed in the steroidogenic cells of the fetal sheep adrenal, suggesting that IGF-II may be an important regulator of fetal adrenal function. However, the regulation of IGF-II gene expression is poorly understood. In the present study we measured the changes in IGF-II mRNA level in fetal sheep adrenals during late gestation in response to ACTH and cortisol. Either saline (0.5 ml/h) or cortisol (1 mg/24 h) was infused for 100 h to fetal sheep beginning on day 95 or 96 of pregnancy, or saline (0.5 ml/h), ACTH (0.5 micrograms/h) or cortisol (1 mg/h) was infused for 84 h to fetal sheep beginning on days 120-125 of pregnancy (term = 145 days). Adrenal RNA was subjected to Northern blot analysis with an ovine IGF II cDNA probe. The relative abundance of total IGF-II mRNA decreased significantly in the ACTH- and cortisol-treated fetuses. IGF-II mRNA was localized by in situ hybridization using a 35S-labeled antisense ovine IGF-II cRNA probe, and IGF-II peptide was localized by immunohistochemistry. There were no differences in the cellular distribution patterns of IGF-II mRNA and IGF-II peptide after treatments, but the intensity of the hybridization signal for IGF II mRNA and of immunostaining for IGF-II peptide decreased in adrenals from fetuses treated with ACTH or cortisol. These results suggest that ACTH and cortisol decrease IGF-II gene expression in the ovine fetal adrenal. We speculate that the cortisol surge observed in the late gestation ovine fetus may be responsible for down-regulation of IGF-II gene expression in the fetal adrenal at or just before birth. PMID- 8194489 TI - Preferential induction of c-fos immunoreactivity in vasoactive intestinal polypeptide-innervated gonadotropin-releasing hormone neurons during a steroid induced luteinizing hormone surge in the female rat. AB - In small rodents, reproduction is critically dependent on the integrity of the circadian oscillator of the brain, the suprachiasmatic nucleus (SCN). Lesions of the SCN induce persistent estrus (anovulation) in intact female rats, whereas estrogen implantation in ovariectomized rats results in daily LH surges, which disappear after SCN lesions. Vasoactive intestinal polypeptide (VIP), a peptide synthesized in cell bodies of the SCN, has been implicated in the regulation of LH release. Recently, we have provided immunocytochemical evidence for a VIP containing neuronal projection from the SCN to the GnRH system. This suggests that VIP from the SCN may modulate LH release via a direct influence on GnRH neurons. To investigate the involvement of VIP input on GnRH neurons and SCN neurons in the generation of a LH surge, we used immunoreactive c-fos as a marker for cell activation in ovariectomized mature rats and immature rats treated with steroids. VIP-containing fibers were observed in apposition to a substantial portion of the GnRH neurons containing c-fos. Expression of c-fos was more frequently observed in VIP-innervated GnRH neurons than in GnRH neurons in general. This difference in activation was most pronounced during the onset of the LH surge. In SCN neurons, steroid treatment did not induce c-fos immunoreactivity before or during the LH surge. The present results indicate that VIP-containing fibers, possibly originating in the SCN, are involved in the initiation of the LH surge. In view of the reported inhibitory effects of VIP on LH release, it is suggested that the role of VIP input in this respect is permissive. PMID- 8194490 TI - Molecular characterization and in situ localization of murine endoglin reveal that it is a transforming growth factor-beta binding protein of endothelial and stromal cells. AB - Endoglin is an integral membrane glycoprotein predominantly expressed on human endothelial cells and recently shown to bind transforming growth factor-beta 1 (TGF beta 1) with high affinity. We now report the cloning and sequencing of a full-length murine endoglin complementary DNA of 2902 base pairs which hybridizes specifically with a single messenger RNA (mRNA) species. The polypeptide of 653 amino acids has an overall identity of 72% with human and porcine endoglin. The transmembrane and cytoplasmic domains of all three proteins differ by two to four amino acids and are 70% identical to the corresponding regions of the TGF beta binding protein, betaglycan. Relative levels of murine endoglin mRNA were estimated by polymerase chain reaction and found to be high in ovary and uterus, intermediate in heart and muscle, and low in placenta and spleen. In situ hybridization and immunofluorescence confirmed that murine endoglin, like its human counterpart, is present in blood vessels and capillaries in all tissues examined. In addition, the stromal cells in the connective tissue of intestine, stomach, heart, muscle, uterus, ovary, and testis were strongly and specifically reactive with complementary RNA probes and with a polyclonal antibody to endoglin; epithelial cell layers were distinctly unreactive. This distribution is similar to that of extracellular TGF beta 1, particularly in heart and uterus, and suggests that endoglin on stromal fibroblast-like cells might be regulating access of TGF beta 1 to the signaling receptor complex. NCTC-2071 fibroblasts in culture were shown to express high levels of endoglin mRNA by polymerase chain reaction. After chemical cross-linking with [125I]TGF beta 1 and immunoprecipitation with the polyclonal antihuman endoglin serum, a radiolabeled band of mol wt 180,000 corresponding to dimeric endoglin was observed under nonreducing conditions, whereas a single band of mol wt 90,000 was seen under reducing conditions. Thus murine fibroblast endoglin is capable of binding TGF beta 1. Future studies should establish the specialized role of endoglin in the TGF beta receptor complex of endothelial and stromal cells. PMID- 8194491 TI - The retinoic acid and retinoid X receptors are differentially expressed during myoblast differentiation. AB - Retinoids (all trans and 9-cis retinoic acid) are pleiotropic regulators of cell fate, and have been shown to regulate the expression of helix loop helix transcription factors (e.g MyoD, myogenin and Myf-5) that control myogenic differentiation. The effects of retinoids are mediated through the ligand dependent retinoic acid receptors (RARs) and retinoid X receptors (RXRs). We have found that the messenger RNA transcripts encoding RAR are repressed during differentiation of C2C12 myoblasts while, conversely, RXR mRNA transcripts are induced in C2C12 myotubes. These results imply that RXRs, play a major regulatory role in differentiated muscle. PMID- 8194492 TI - The Inter-regional Belgian Bank Employee Nutrition Study (IBBENS). AB - OBJECTIVE: This study compares the dietary intake in different geographical areas in Belgium. DESIGN: Food habits were examined by the 3-day food record with additional intervieW. SETTING: The study was performed in the head offices of one bank situated in seven Dutch-speaking cities (spread over two districts) in the north and one French-speaking city in the south of Belgium. SUBJECTS: 371 male and 192 female healthy employees participated in the survey. RESULTS: The results show a difference in fat consumption between north and south. Men in the French speaking district consumed on average 18.8 E% (SD = 3.2) of saturated fat, compared to 16.2 (2.8) and 16.7 (2.9) E% for the two Dutch-speaking districts (P < 0.001). For women the respective data are 18.9 (3.2), 16.4 (3.0) and 17.1 (3.1) E% (P < 0.01). The E% of polyunsaturated fat in the three districts equals respectively 5.2 (1.8), 7.2 (2.4) and 6.7 (2.5) (P < 0.001) for men; 4.9 (1.8), 7.2 (2.7) and 6.6 (2.2) (P < 0.001) for women. A significantly lower P/S ratio (P < 0.001, for both sexes) and U/S ratio (P < 0.001, for both sexes) was found in the south. The intake of cholesterol (mg per 4.18 MJ) was significantly higher in the south (P = 0.01, for both sexes). The differences between the Dutch-speaking centres were relatively small. For men significant differences in P/S ratio, 0.48 (0.22) in the east versus 0.43 (0.20) in the west (P < 0.001), and in E% of monounsaturated fat, 15.2 (2.7) versus 16.3 (3.1) (P < 0.01), could be established. CONCLUSION: Differences in fat intake exist between the north and the south of Belgium. Within the north significant differences exist in P/S ratio and in intake of monounsaturated fat. PMID- 8194493 TI - Requirement and supply of vitamin C, E and beta-carotene for elderly men and women. AB - OBJECTIVES: To study the effect of age, smoking, alcohol consumption on the requirement of vitamin C, beta-carotene and alpha-tocopherol. DESIGN: The participants of this cross-sectional survey were recruited from a multistaged, stratified random household sample in 1987/88. SUBJECTS: 2006 healthy men and women aged 18-88 years, living in private homes. The participation rate was approximately 70%. Vitamin intake data were calculated from an estimated 7-day food record. SETTING: Nationwide German Nutrition Survey. RESULTS: At the same vitamin C intake levels, elderly, non-smoking men have lower plasma vitamin C levels than younger men. This age-effect was markedly stronger in smokers, indicating that elderly men may need more vitamin C in their diet to achieve comparable plasma levels of young adults. Plasma beta-carotene levels are reduced substantially among smokers and to some extent among heavy alcohol drinkers below levels due to differences in the carotene intake. At the same carotene intake levels, elderly smokers seem to have reduced plasma beta-carotene levels as compared with young adults. After adjusting for blood lipids and vitamin E intake the alpha-tocopherol plasma levels seem not to be associated with age. CONCLUSION: This study supports the hypothesis that with age the requirement for vitamin C and possibly for beta-carotene increases and that the requirement for vitamin E is not altered by age. PMID- 8194494 TI - Similar serum lipoprotein cholesterol concentrations in healthy subjects on diets enriched with rapeseed and with sunflower oil. AB - A double-blind cross-over study was conducted during two 3-week periods to compare the effects of rapeseed oil and sunflower oil, enriching a normal diet, on the lipoprotein and fatty acid composition in healthy subjects. It was carried out in randomized order at residential schools, comprising 101 persons (mean age 29.2 years). The dietary fats used for cooking and as table margarine were prepared from rapeseed oil during one period and from sunflower oil during the other. No changes were made in the total fat content or other dietary nutrients. During both treatment periods the serum cholesterol (-4%, P < 0.001), LDL cholesterol (-5% to -7%, P < 0.01 and 0.001) and apolipoprotein B (-5%, P < 0.001) concentrations decreased significantly and to the same extent, while serum triglycerides, HDL cholesterol, apolipoprotein A-1 and lipoprotein (a) remained virtually unchanged. The content of 18:2 n-6 serum phospholipids was increased after the sunflower oil-enriched diet, and the contents of oleic acid (18:1 n-9), alpha-linolenic acid (18:3 n-3), and eicosapentaenoic acid (20:5 n-3) were increased after the rapeseed oil-enriched diet. The concentration of alpha tocopherol increased and gamma-tocopherol decreased after the sunflower oil enriched diet, less so after the rapeseed oil-enriched diet. It is concluded that substitution of mono- and polyunsaturated fats for saturated fats without any other dietary changes causes a significant improvement of the lipoprotein profile in healthy subjects. The rapeseed oil and sunflower oil fats were equally effective in this respect. The results also indicate that humans have a certain capacity to elongate and desaturate alpha-linolenic acid to 20:5 n-3 in vivo. Dietary fats based on rapeseed oil seem to be attractive alternatives to the more commonly used oils and fats rich in linoleic acid. Financial support from the Swedish Council for Forestry and Agricultural Research and the Swedish Margarine Industrial Association for Nutritional Physiological Research is gratefully acknowledged. PMID- 8194495 TI - Energy restriction, a useful intervention to retard human ageing? Results of a feasibility study. AB - OBJECTIVE: Energy restriction (ER) retards the ageing process in animal models. It is possible that ER has a similar effect in humans. As a first approach to look after the potential application of ER in man the feasibility of a moderately energy-restricted diet was studied. DESIGN: A controlled intervention study. SETTING: TNO Toxicology and Nutrition Institute. SUBJECTS: 24 middle-aged non obese men, selected from men responding to advertisements in regional newspapers. INTERVENTIONS: After a run-in period subjects were divided into two groups, a control group (n = 8) and an ER group (n = 16). Groups were matched on age and body mass index. The effects of 10 weeks of moderate ER (80% of habitual energy intake) on body composition, general health (blood pressure, lipid profile, routine clinical chemistry and haematology), physical and mental performance, and feelings of hunger, satiety and state of mind were measured. RESULTS: Subjects in the ER group lost about 7.4 +/- 2.6 kg weight (P < 0.001). This weight loss concerned mainly loss of fat mass. Diastolic and systolic blood pressure decreased significantly within the ER group (P < 0.05 and P < 0.01 respectively). The increase in HDL-cholesterol level was significantly related to weight loss (P < 0.05). CONCLUSIONS: The results show beneficial effects of 10 weeks of moderate ER on blood pressure and lipid profile without adverse effects on physical and mental performance and feelings of hunger, satiety and mood. PMID- 8194496 TI - Control of longitudinal growth: the role of nutrition. PMID- 8194497 TI - Dietary studies on two rural Italian population groups of the Seven Countries Study. 1. Food and nutrient intake at the thirty-first year follow-up in 1991. AB - The food and nutrient intake at the thirty-first follow-up in 1991 of 16 surviving elderly from Crevalcore and Montegiorgio, two Italian rural ares of the Seven Countries Study, are reported. For dietary appraisal the individual weighed record method for 3 and 9 days in three seasons was used. In autumn the dietary history method was also used. Because the number of survivors was small, 15 additional elderly subjects in both areas were surveyed. Then, to detect any change related to age in food intake, 41 younger subjects were assessed with the dietary history method. The results in both areas showed in general a high intra individual variability and no statistically significant difference in food group and nutrient intake between seasons. Between the two methods for dietary survey no statistically significant difference, in general, was observed (P > 0.05 only for a few items). The diet of the subjects of Crevalcore was characterized by a rather high intake of milk and meat and a low intake of fish and legumes. In Montegiorgio the picture was similar to that of Crevalcore, but at a lower level of intake. In both areas, but particularly in Montegiorgio, these subjects have been abandoning the traditional Mediterranean diet. PMID- 8194499 TI - Food and nutrient intakes and eating patterns in functional and organic dyspepsia. AB - Forty organic dyspepsia patients and 40 functional dyspepsia patients, endoscopically diagnosed, were recruited from a gastroenterology outpatient unit and were age- and sex-matched with an equal number of patient controls. A diet history of typical eating patterns for a 7-day period was taken and food portions quantified using a photographic atlas. An interviewer-assisted questionnaire was used to identify present eating habits, dietary patterns reported to exacerbate or relieve symptoms and alterations in eating habits as a result of symptoms. Females with organic or functional dyspepsia reported significantly lower energy intakes (P < 0.01) than controls. Females with organic dyspepsia had significantly lower intakes of fat, carbohydrate, fibre and a wide range of micronutrients compared to controls. Females with functional dyspepsia had significantly lower intakes of fat, sugars and vitamin C (P < 0.05) than controls. Organic dyspepsia patients (male and female) had significantly lower intakes of alcohol and vitamin C than controls (P < 0.05). Patients with organic dyspepsia had higher intakes of milk and lower intakes of fresh fruit and/or fruit juice than controls. The main difference in eating pattern noted was that a significantly lower percentage (P < 0.05) of functional dyspepsia patients than controls regularly ate three meals per day. Large numbers of dyspepsia patients in both groups associated certain eating habits and the consumption of specific foods with exacerbation of dyspeptic symptoms and over 80% of both groups reported food avoidance as a result of this.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194498 TI - Dietary studies on two rural Italian population groups of the Seven Countries Study. 2. Concurrent validation of protein, fat and carbohydrate intake. AB - On 18 subjects from two rural areas in Italy which were part of the Seven Countries Study (Crevalcore and Montegiorgio), we carried out the concurrent validation of protein, fat, fatty acid and carbohydrate intake in the diet at the thirty-first year follow-up in 1991. The values of the above nutrients obtained using food composition tables from the weighted record method for dietary surveys were compared with the values from chemical analysis of food composites. In both areas for protein, fat and carbohydrate intake the inter-individual variation was large. For protein intake the mean difference was statistically significant but not for fat intake. From 1960 to 1991 protein and fat intake tended to decrease and for protein the means of differences between analysis and calculation were, in general, statistically different. For dietary saturated and polyunsaturated fatty acids, the means of differences were statistically significant in Crevalcore, but this was not the case in Montegiorgio for polyunsaturated fatty acids. The intake of trans fatty acids in both areas was rather low. Available and unavailable carbohydrate intake of both areas showed no statistically significant difference. The mean differences between analysis and calculation for both areas were statistically significant with the exception of cellulose in Crevalcore and sugars in Montegiorgio. PMID- 8194500 TI - Bioavailability of starch in bread products. Postprandial glucose and insulin responses in healthy subjects and in vitro resistant starch content. AB - Attempts to reduce glycaemia to bread were evaluated in healthy subjects. The contents of in vitro resistant starch (RS) were also measured in the bread products. The potential of including intact barley kernels at different concentrations (80% and 40%) was tested in two products (SCB-80 and SCB-40). Three variants of barley bread made from wholemeal were also studied: ordinary (WMB), sourdough fermented (WMB-s) and one made from scalded flour (SWMB). A commercial pumpernickel bread (PB) based on sourdough fermented rye kernels was included for comparison and a white wheat bread (WWB) used as reference for calculation of glycaemic index. The glycaemic and insulinaemic indices for SCB-80 were 33 and 39, and for PB 69 and 61, respectively. The glycaemic index was lowered also in case of SCB-40 (66). No differences in indices were found between the WMB products or versus WWB. A high content of RS (8% starch basis) was found in the PB product, compared with the remaining bread products (0.8-1.7%). PMID- 8194501 TI - Estimation in community surveys of total body fat of children using bioelectrical impedance or skinfold thickness measurements. AB - OBJECTIVE: To compare skinfold thickness measurements with bioelectrical impedance analysis (BIA) as a measure of body fat for use in a survey of children (the National Study of Health and Growth). DESIGN: Part cross-sectional, part repeated measurement study. SETTING: A junior school in Bath. SUBJECTS: 42 boys and 33 girls aged from 9 to 11 years. INTERVENTIONS: Measurements of BIA, height, weight, and triceps, biceps, subscapular and suprailiac skinfolds. RESULTS: All measurements were highly repeatable with intraclass correlation coefficients > 0.90. The level of agreement between estimates of percentage of body fat derived from prediction equations based on impedance or skinfold measurements respectively was poor: the mean difference (impedance estimate minus skinfold estimate) was 4.67% (95% range -3.47 to 12.82) for boys and 7.81% (95% range 1.27 to 14.34) for girls. The two estimates were found to correlate highly (r = 0.83 for boys and r = 0.81 for girls) because weight, used to convert estimates of fat free mass derived from impedance to fat mass, was highly correlated with impedance and moderately highly correlated with skinfold thicknesses. The correlations of resistance (R) and (H)2/R with skinfold thicknesses were very low. There was a moderate correlation of R and H2/R with log(weight-for-height index), but lower than that of log(weight-for-height index) with each of the skinfolds. CONCLUSIONS: As currently available equations for converting impedance based estimates of total body water to fat mass are not fully developed for use in children of varying ages, estimates of body fat calculated from skinfold thickness measurements remain preferable in epidemiological studies of children's health and growth. PMID- 8194502 TI - Effects of two kinds of decaffeinated coffee on serum lipid profiles in healthy young adults. AB - OBJECTIVE: To investigate the effects of two kinds of decaffeinated coffee on serum lipid profiles in healthy young adults. DESIGN: Randomized controlled study with three study groups and a parallel design, consisting of two consecutive periods. SETTING: Outpatient clinical research center in a university clinic. SUBJECTS: 119 healthy students (60 male, 59 female) who were selected after a screening. All completed the study. Blood samples of three subjects (1 male, 2 female) were excluded from evaluation due to later diagnosed genetic anomalies of lipid metabolism. INTERVENTIONS: All subjects consumed 750-1000 ml of caffeinated filtered coffee per day for a 2 week wash-in period. During the 6 week test period one group continued drinking the caffeinated coffee, while the two other groups consumed different kinds of decaffeinated coffee. RESULTS: Consumption of both types of decaffeinated coffee did not lead to any significant changes in serum total and LDL cholesterol, triglycerides and apolipoprotein B. Furthermore, there were no significant differences in the reactions between the three groups. The diet did not change during the study. CONCLUSIONS: Switch from regular to decaffeinated coffee had no cholesterol-elevating effects, irrespective of the type of coffee. PMID- 8194503 TI - Agreement between interview data and a self-administered questionnaire on dietary supplement use. AB - OBJECTIVE: To study the relative validity of an open-ended question on the consumption of dietary supplements in the preceding five-year period, incorporated in a self-administered questionnaire used in the NLCS, The Netherlands Cohort Study on diet and cancer (120,852 men and women aged 55-69 years). DESIGN: Questionnaire data were compared with reference information from three personal interviews carried out within a period of 10 months. SETTING AND SUBJECTS: A randomly selected subgroup (59 men and 50 women) of the cohort living in 12 municipalities in the eastern and western regions of The Netherlands. RESULTS AND CONCLUSIONS: The overall sensitivity of the questionnaire concerning the use of any dietary supplement was 65.9%, the specificity was 98.5%; kappa as measure of agreement was estimated at 0.69. A high percentage recall was observed among women, users of at least three types of dietary supplements, long-term supplement users and those in the oldest age group. Recall of intake of specific supplements ranged from 77.8% for garlic preparations to 11.8% for 'other' supplements. Estimates of consumption of specific supplements (garlic and vitamin preparations) may provide enough precision to correctly classify individuals as users or non-users of those supplements. PMID- 8194504 TI - Anthropometry as a predictor for mortality among Ugandan children, allowing for socio-economic variables. AB - Length, height, weight and mid-upper arm circumference (MUAC) were measured in 4320 children aged between 0 and 59 months, and their socio-economic status was assessed, in 31 villages in Southwest Uganda during March-April 1988. A follow-up survey assessed the mortality of the children during the 12 months following anthropometry. Mortality rates were higher in those with low anthropometric indices at the first survey. MUAC was the most sensitive predictor of mortality followed by weight-for-age, height-for-age and weight-for-height. MUAC increased the predictive power of other parameters whereas the other parameters did not increase the predictive power of MUAC. MUAC below 12.5, 11.5 and 10.5 cm predicted 10.9%, 18.7% and 36.5% of the deaths respectively. Nutritional status was worse in the low socio-economic group but the predictive power of anthropometry for mortality was not influenced by socio-economic status. This suggests that nutrition per se has an influence on mortality which is independent of socio-economic status. PMID- 8194505 TI - The effect of calcium carbonate and calcium citrate on the absorption of zinc in healthy female subjects. AB - OBJECTIVES: The aim of this study was to determine the effect of calcium carbonate and calcium citrate on zinc absorption. DESIGN: The zinc tolerance test (ZTT), which is the plasma zinc response to an oral zinc challenge, was used to quantitate zinc absorption. A physiological test dose of zinc (4.5 mg elemental zinc as 20 mg zinc sulphate) was used. Subjects underwent ZTTs on three separate occasions, each time consuming in random order, either 4.5 mg elemental zinc, zinc with 600 mg elemental calcium as calcium carbonate or zinc with 600 mg elemental calcium as calcium citrate. SETTING: Metabolic ward conditions. SUBJECTS: Nine, free-living, healthy female subjects recruited from the University population. INTERVENTIONS: Blood samples were obtained at 30 min intervals for 4 h postdose. RESULTS: The area under the plasma zinc curve (AUC) (mean +/- SEM) following the coingestion of zinc with calcium carbonate (438.4 +/ 129.0 mumol Zn.min/100 g albumin) and calcium citrate (308.0 +/- 110.5) was significantly lower (P < 0.017) than when zinc was ingested alone (1561.7 +/- 240). Urinary excretion of calcium was significantly higher (P < 0.017) at 4 h after supplementation with calcium citrate (0.83 +/- 0.12 mumol Ca/mumol creatinine) compared with calcium carbonate (0.40 +/- 0.11). CONCLUSIONS: The decrease in zinc absorption following the ingestion of zinc with different forms of calcium suggests that an antagonistic competition occurred between the minerals and that elemental calcium is the inhibiting factor. PMID- 8194506 TI - Basal metabolic rate and body fatness of adult men in northern Mexico. AB - To investigate the possibility that overprediction of basal metabolic rate (BMR) of tropical populations is related to differences in fatness between tropical and temperate populations, 32 Mexican men aged 18-40 years underwent measurements of BMR and body fat content. The men were divided into four body mass index (BMI) groups (< 20, 20-25, 25-30 and 30-40). The mean weight was 78 (range 52-119) kg and the mean height was 1.75 (range 1.61-1.89) m. BMR was measured in the subjects after an overnight stay in a residential unit by a Deltatrac ventilated hood indirect calorimetry system. Body fat content was determined by 2H2O dilution. The relationship between BMR and body weight was analysed by linear regression and the equations derived were compared to the values predicted using the FAO/WHO/UNU (1985) equations. The FAO/WHO/UNU equations overestimated measured BMR by 9.8%, 9.6%, 7.8% and 5.5% in the four groups. The overall difference was 8.2%, which was statistically significant (P < 0.001). The intercepts of the two equations were significantly different (P < 0.001) by 532 kJ/day, but there was no significant difference between the slopes of the two regression equations. There was no significant difference between BMR/kg fat-free mass in the four BMI groups. The results therefore do not support the possibility that the overprediction of BMR in tropical populations by international prediction equations based on body weight is accounted for by differences in fatness between tropical and temperate populations. PMID- 8194507 TI - Tocopherol concentrations in adipose tissue. Relationships of tocopherol concentrations and fatty acid composition in serum in a reference population of Swedish men and women. AB - The tocopherol concentrations in serum and adipose tissue were studied in relation to the fatty acid composition and clinical characteristics in 110 subjects. The tocopherol concentrations in adipose tissue showed large interindividual variations and were positively correlated to those in serum (r = 0.24-0.31, P < 0.01) but did not increase with age. The ratio between alpha- and gamma-tocopherol in adipose tissue was only about half of that in serum. In serum, but not in adipose tissue, the alpha-tocopherol and linoleic acid concentrations were positively correlated. Serum apolipoprotein B was inversely correlated to lipid-corrected serum alpha-tocopherol (r = -0.22, P = 0.03), indicating decreasing oxidative protection with increasing blood lipids. Measurement of the serum tocopherol concentration in addition to that of the serum lipoprotein concentration may be of value in estimating the risk for coronary heart disease. Whether measurement of the tocopherol concentration in adipose tissue has any advantage over that in serum remains to be determined. PMID- 8194508 TI - Urinary zinc as a marker of zinc intake: results of a supplementation trial in free-living men. AB - Twenty-four adult male volunteers were asked to ingest 50 or 100 mg elemental zinc (as zinc sulphate) for 7 days. The design was a randomized cross-over trial with a 3 week wash-out period. A significant increase in 24 h urinary zinc excretion occurred after supplementation with 100 mg with a change from 48.0 +/- 4.6 (mg Zn/mmol creatinine, mean +/- SE) at day 0 to 82.6 +/- 15.9 at day 7 (P < 0.05). No significant change was observed following supplementation with 50 mg zinc. Taken together with published data, this suggests urinary zinc excretion is sensitive only to extreme changes in dietary zinc intake. PMID- 8194509 TI - Chronic pretreatment with naloxone modifies benzodiazepine receptor binding in amygdaloid kindled rats. AB - Male Sprague-Dawley rats received either naloxone (75 micrograms/h) or saline (0.5 microliter/h) s.c. for 14 days delivered with osmotic minipumps. Two days after termination of either treatment, daily amygdala kindling stimulation was applied until the animals experienced stage V kindled seizures. Benzodiazepine (BDZ) binding sites were labeled with [3H]flunitrazepam (2 nM), and changes in specific brain areas were determined by in vitro quantitative autoradiography. Twenty-four hours after the last electrical stimulation, the saline pretreated fully kindled rats showed enhanced BDZ receptor binding in dentate gyrus, and decreased binding in cingulate cortex ipsilateral to the stimulation compared to saline controls. Twenty-eight days after the last stage V kindled seizure, the significant alterations were no longer evident. In agreement with a previous study, we found that naloxone pretreated amygdala kindled rats showed stage V kindled seizures followed by intervals of 3-5 days in which the same electrical stimulation failed to induce any behavioral and EEG alterations. In comparison with the saline pretreated kindled and saline control groups, the naloxone pretreated kindled rats had significantly higher BDZ binding in different cortical areas, amygdala complex, hippocampus, substantia nigra and periaqueductal gray, 24 h after the last electrical stimulation. The present study indicates that previous chronic exposure to naloxone increases BDZ receptor binding in kindled rats, and suggests that this effect may be associated with the enhanced seizure suppression observed in these animals. PMID- 8194510 TI - The NMDA antagonist MK-801 suppresses behavioral seizures, augments afterdischarges, but does not block development of perforant path kindling. AB - The role of N-methyl-D-aspartate (NMDA) in the development and expression of kindled seizures was assessed using a crossover design. Rats were stimulated once daily in the perforant path for 10 consecutive days 30 min following daily administration of saline or the NMDA antagonist MK-801 (1.0 mg/kg) (phase I). Five to 10 days elapsed prior to an additional 10 stimulations with the drug treatments reversed (phase II). A separate group of animals was stimulated following saline administration in both phases of the study. MK-801 produced a significant increase in afterdischarge (AD) threshold and a suppression of behavioral seizure development during the first 10 stimulations. However, upon removal of the drug, an immediate increase in seizure stage and the number of animals displaying generalized seizure signs (clonic component) was observed. Paradoxically, MK-801 also produced an increase in mean AD duration in the perforant path and dentate gyrus over the first 10 stimulations. Upon reversal of the dose treatments in phase II of the study, AD duration increased in animals treated with MK-801 for the first time, and decreased in animals taken off MK-801 and stimulated drug free. The augmentation in AD associated with MK-801 was partially attributed to an increase in secondary or rebound AD. Rebound ADs occurred more frequently, had a decreased latency and longer duration in drugged compared to control animals, irrespective of the phase of the study. These data indicate that MK-801 possesses anticonvulsant properties with respect to behavioral seizure, and is less effective as an antiepileptogenic agent-i.e., significant kindling development occurred with MK-801 in the absence of overt behavioral expression of the kindled response. A dissociation between seizure stage and AD duration suggests that independent mechanisms may control the electrographic and behavioral indices of kindling. PMID- 8194511 TI - A microdialysis study of amino acid concentrations in the extracellular fluid of the substantia nigra of freely behaving GEPR-9s: relationship to seizure predisposition. AB - Substantia nigra (SN) is known to play an important role in seizure generalization. Both excitatory and inhibitory neurotransmitters can modulate this role of SN. Previous studies have shown that GABA as well as aspartate and glutamate participate in seizure regulation through this site. Evidence for such a role comes from studies on the genetically epilepsy-prone rat (GEPR) and other seizure models. In the GEPR, bilateral microinjections of NMDA receptor antagonists in SN block or reduce seizure severity. In order to further evaluate which neurotransmitters are specifically involved at the SN level of seizure regulation in the GEPR, we undertook a microdialysis study of K+ stimulated release of amino acids in the SN of GEPR-9s- and non-epileptic controls. A 1 mm loop-type microdialysis probe was inserted through pre-implanted guides into the SN of awake and freely moving rats (seven GEPR-9s and four non-epileptic controls), and used to perfuse a 100 mM K+ (high K+) solution for 2 h. Four 30 microliters samples were collected prior to high K+ stimulation (basal release), during high K+ perfusion, and after high K+ infusion. After precolumn derivatization with phenylisothiocyanate, levels of aspartic (ASP) and glutamic (GLU) acids, glycine (GLY), taurine (TAU) and GABA were measured by reversed phase high performance liquid chromatography. Two hours after the initiation of high K+ infusion, the increases relative to basal were, for non-epileptic controls, 35%, 74%, 68%, 847% and 283% respectively for ASP, GLU, GLY, TAU and GABA. Corresponding increases for GEPR-9s were 14%, 10%, 41%, 505% and 123% respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194512 TI - The effect of the non-NMDA receptor antagonist GYKI 52466 and NBQX and the competitive NMDA receptor antagonist D-CPPene on the development of amygdala kindling and on amygdala-kindled seizures. AB - A competitive (NBQX) and a non-competitive (GYKI 52466) AMPA antagonist, and a competitive NMDA antagonist (D-CPPene) were tested against the development of kindling and against fully kindled seizures in amygdala-kindled rats. GYKI 52466, 10 mg/kg given i.p. 5 min prior to electrical stimulation in fully kindled animals, reduces both the cortical after-discharge duration and the behavioural seizure score. GYKI 52466, 20 mg/kg, reduces seizure score and after-discharge duration significantly (after 5-30 min) but the animals show severe motor side effects and an irregular cortical and hippocampal EEG. Administration of GYKI 52466, 10 mg/kg, prior to kindling stimulation on days 3-8, does not slow the development of kindling. NBQX, 20 mg/kg or 40 mg/kg i.p., 30 min prior to stimulation, significantly reduces the seizure score in fully kindled animals. NBQX 20 mg/kg i.p. has no effect on the development of kindling. D-CPPene, 8 mg/kg or 12 mg/kg, 120 min prior to stimulation reduces the behavioural seizure score in fully kindled animals. D-CPPene, 8 mg/kg on days 3-8, delays the development of kindling. NMDA receptors play a key role in the kindling process. Expression of kindled seizures involves non-NMDA and NMDA receptors. PMID- 8194513 TI - Limbic encephalitis: a case report. AB - We report a case of a 24 year old patient, who presented with simple and complex partial epileptic seizures, progressive changes in behaviour and affect including marked aggression, and a decline in memory to the point of inability to learn. Extensive work-up resulted in a final diagnosis of limbic encephalitis. This diagnosis was supported by a number of investigations performed during the follow up of 6 years and ranging from the basic EEG to the more sophisticated investigations of magnetic resonance tomography, magnetoencephalography and positron emission tomography. PMID- 8194514 TI - Strategies in antiepileptic drug development: is rational drug design superior to random screening and structural variation? PMID- 8194515 TI - Crystal structure of a human rhinovirus neutralizing antibody complexed with a peptide derived from viral capsid protein VP2. AB - The three-dimensional structure of the complex between the Fab fragment of an anti-human rhinovirus neutralizing antibody (8F5) and a cross-reactive synthetic peptide from the viral capsid protein VP2 has been determined at 2.5 A resolution by crystallographic methods. The refinement is presently at an R factor of 0.18 and the antigen-binding site and viral peptide are well defined. The peptide antigen adopts a compact fold by two tight turns and interacts through hydrogen bonds, some with ionic character, and van der Waals contacts with antibody residues from the six hypervariable loops as well as several framework amino acids. The conformation adopted by the peptide is closely related to the corresponding region of the viral protein VP2 on the surface of human rhinovirus 1A whose three-dimensional structure is known. Implications for the cross reactivity between peptides and the viral capsid are discussed. The peptide antibody interactions, together with the analysis of mutant viruses that escape neutralization by 8F5 suggest two different mechanisms for viral escape. The comparison between the complexed and uncomplexed antibody structures shows important conformational rearrangements, especially in the hypervariable loops of the heavy chain. Thus, it constitutes a clear example of the 'induced fit' molecular recognition mechanism. PMID- 8194516 TI - Intergeneric complementation of a circadian rhythmicity defect: phylogenetic conservation of structure and function of the clock gene frequency. AB - The Neurospora crassa frequency locus encodes a 989 amino acid protein that is a central component, a state variable, of the circadian biological clock. We have determined the sequence of all or part of this protein and surrounding regulatory regions from additional fungi representing three genera and report that there is distinct, preferential conservation of the frequency open reading frame (ORF) as compared with non-coding sequences. Within the coding region, many of the domain hallmarks of the N. crassa protein are highly conserved, especially an internal region bearing the causative mutations in frq1 and frq7, the most extreme alleles in the frequency allelic series. Despite considerable diversity among the strains analyzed in terms of morphology, growth, circadian clock output and frq sequence, the ORF from the most distantly related fungus included in this study (Sordaria fimicola) rescues rhythmicity in a N.crassa frequency null strain. Both sequence conservation, and the ability of frequency from a genus displaying one developmental program to complement circadian defects in a separate genus with a distinct, clock-regulated developmental program, are consistent with a central role of the frequency gene product in a general circadian oscillator capable of controlling diverse outputs in a variety of systems. PMID- 8194517 TI - Membrane protein topology: effects of delta mu H+ on the translocation of charged residues explain the 'positive inside' rule. AB - The membrane electrochemical potential is critical for the export of most periplasmic proteins in Escherichia coli. Its exact role during insertion of integral inner membrane proteins, however, remains obscure. Using derivatives of the inner membrane protein leader peptidase (Lep), we now show that the membrane potential appears to stimulate the membrane translocation of chain segments containing negatively charged residues, that positively charged regions appear to be more easily translocated in the absence of a potential, and that certain Lep constructs insert with different topologies in the presence and absence of a membrane potential, suggesting that the electrochemical potential introduces an asymmetry between the topological effects of positively and negatively charged amino acids during the process of membrane protein insertion in E. coli. PMID- 8194518 TI - Post-translational alterations in transmembrane topology of the hepatitis B virus large envelope protein. AB - The preS domain at the N-terminus of the large envelope protein (LHBs) of the hepatitis B virus is involved in (i) envelopment of viral nucleocapsids and (ii) binding to the host cell. While the first function suggests a cytosolic location of the preS domain during virion assembly, the function as an attachment site requires its translocation across the lipid bilayer and final exposure on the virion surface. We compared the transmembrane topology of newly synthesized LHBs in the endoplasmic reticulum (ER) membrane with its topology in the envelope of secreted virions. Protease sensitivity and the absence of glycosylation suggest that the entire preS domain of newly synthesized LHBs remains at the cytosolic side of ER vesicles. However, virions secreted from transfected cell cultures or isolated from the blood of persistent virus carriers expose antibody binding sites and proteolytic cleavage sites of the preS domain at their surface in approximately half of the LHBs molecules. Thus, preS domains appear to be transported across the viral lipid barrier by a novel post-translational translocation mechanism to fulfil a dual function in virion assembly and attachment to the host cell. PMID- 8194519 TI - A C-terminal domain conserved in precursor processing proteases is required for intramolecular N-terminal maturation of pro-Kex2 protease. AB - The Kex2 protease of the yeast Saccharomyces cerevisiae is the prototype of a family of eukaryotic subtilisin homologs thought to process prohormones and other precursors in the secretory pathway. Deletion analysis of Kex2 protease shows that a sequence of 154-159 residues carboxyl to the subtilisin domain is essential for the formation of active enzyme. Disruption of this region, termed the 'P-domain', blocks the normally rapid intra-molecular cleavage of the N terminal pro-segment of pro-Kex2 protease in the endoplasmic reticulum (ER). The C-terminal boundary of the P-domain coincides closely with the endpoint of similarity between Kex2 protease and its mammalian homologues. The conservation of and functional requirement for the P-domain sharpens the distinction between a 'Kex2 family' of processing enzymes and degradative 'subtilases', and implies that the Kex2-related enzymes have in common entirely novel structural features that are important in the maturation of precursor polypeptide substrates. Failure to cleave the N-terminal pro-domain, due either to truncation of the P-domain or to mutation of the active site histidine or serine, results in stable, intracellular retention of pro-enzyme, apparently in the ER. Thus pro-Kex2 protease appears to contain an ER retention signal which is removed or destroyed by cleavage of the pro-domain. PMID- 8194520 TI - An alternative protein targeting pathway in Escherichia coli: studies on the role of FtsY. AB - In Escherichia coli, a signal recognition particle (SRP) has been identified which binds specifically to the signal sequence of presecretory proteins and which appears to be essential for efficient translocation of a subset of proteins. In this study we have investigated the function of E. coli FtsY which shares sequence similarity with the alpha-subunit of the eukaryotic SRP receptor ('docking protein') in the membrane of the endoplasmic reticulum. A strain was constructed which allows the conditional expression of FtsY. Depletion of FtsY is shown to cause the accumulation of the precursor form of beta-lactamase, OmpF and ribose binding protein in vivo, whereas the processing of various other presecretory proteins is unaffected. Furthermore, FtsY-depleted inverted cytoplasmic membrane vesicles are shown to be defective in the translocation of pre-beta-lactamase using an in vitro import assay. Subcellular localization studies revealed that FtsY is located in part at the cytoplasmic membrane with which it seems peripherally associated. These observations suggest that FtsY is the functional E. coli homolog of the mammalian SRP receptor. PMID- 8194521 TI - Polarized sorting of the polymeric immunoglobulin receptor in the exocytotic and endocytotic pathways is controlled by the same amino acids. AB - Polarized epithelial cells can sort plasma membrane proteins to the apical or basolateral domain either by direct targeting from the trans-Golgi network (TGN) or by targeting to one surface, followed by endocytosis and transcytosis to the opposite surface. In Madin-Darby canine kidney (MDCK) cells, targeting of the polymeric immunoglobulin receptor (pIgR) to the basolateral surface is controlled by a sorting signal residing in the membrane proximal 17 amino acids of the cytoplasmic domain of this receptor. We have recently found that individual mutations at any of three residues in this signal, His656, Arg657 and Val660, substantially decrease targeting from the TGN to the basolateral surface and correspondingly increase targeting from the TGN to the apical surface. Here we report that these mutations decrease the recycling of basolaterally endocytosed pIgR to that surface, and correspondingly increase its transcytosis to the apical surface. This effect occurred in mutant pIgRs that either contained the full length cytoplasmic domain or were truncated to contain only the 17-residue basolateral targeting signal, and was independent of phosphorylation of pIgR at Ser664. Our results indicate that polarized sorting of the pIgR in the endocytotic and exocytotic pathways are controlled by the same amino acids. PMID- 8194522 TI - Retrieval of TGN proteins from the cell surface requires endosomal acidification. AB - TGN38 is a protein of unknown function located in the trans-Golgi network (TGN) of mammalian cells. Its intracellular distribution is maintained by it being continuously retrieved from the plasma membrane. In this paper we show that when cells are treated with agents such as chloroquine which neutralize acidic organelles, the movement of TGN38 along the endocytic pathway is blocked. The same effect is observed with a second TGN protein, the protease furin. We show that the cytoplasmic tail of furin is sufficient to confer a chloroquine sensitive TGN localization on a heterologous protein. These results imply that the internal pH of endosomes affects sorting processes mediated by signals in the cytoplasmic portion of proteins and have implications for the role of acidification in endosomal function. PMID- 8194523 TI - Involvement of phosphoinositide 3-kinase in insulin- or IGF-1-induced membrane ruffling. AB - Insulin, IGF-1 or EGF induce membrane ruffling through their respective tyrosine kinase receptors. To elucidate the molecular link between receptor activation and membrane ruffling, we microinjected phosphorylated peptides containing YMXM motifs or a mutant 85 kDa subunit of phosphoinositide (PI) 3-kinase (delta p85) which lacks a binding site for the catalytic 110 kDa subunit of PI 3-kinase into the cytoplasm of human epidermoid carcinoma KB cells. Both inhibited the association of insulin receptor substrate-1 (IRS-1) with PI 3-kinase in a cell free system and also inhibited insulin- or IGF-1-induced, but not EGF-induced, membrane ruffling in KB cells. Microinjection of nonphosphorylated analogues, phosphorylated peptides containing the EYYE motif or wild-type 85 kDa subunit (Wp85), all of which did not inhibit the association of IRS-1 with PI 3-kinase in a cell-free system, did not inhibit membrane ruffling in KB cells. In addition, wortmannin, an inhibitor of PI 3-kinase activity, inhibited insulin- or IGF-1 induced membrane ruffling. These results suggest that the association of IRS-1 with PI 3-kinase followed by the activation of PI 3-kinase are required for insulin- or IGF-1-induced, but not for EGF-induced, membrane ruffling. PMID- 8194524 TI - Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/CD9, which up-regulates functional receptors and diphtheria toxin sensitivity. AB - DRAP27, the monkey homolog of human CD9 antigen (DRAP27/CD9) and diphtheria toxin receptor (DTR) were expressed in mouse L cells. L cells transfected transiently with both DRAP27/CD9 and DTR cDNA bound approximately 10 times more diphtheria toxin (DT) than cells transfected with DTR alone. Stable L cell transfectants expressing both DTR and DRAP27/CD9 (LCH-1 cells) had 15 times more cell surface DT-binding sites and were 20 times more sensitive to DT than were stable L cell transfectants expressing DTR alone (LH-1 cells). Increased DT-binding and DT sensitivity were not due to increased DTR transcription or increased cell surface DTR protein. Co-immunoprecipitation of DRAP27/CD9 with DTR and chemical cross linking suggest a tight association of these membrane-bound proteins. In addition, the identity of DTR and a growth factor (HB-EGF) was established. Immobilized DT specifically adsorbed HB-EGF precursor solubilized from transfected L cells and [125I]DT bound to immobilized recombinant HB-EGF. We conclude that DRAP27/CD9 associates tightly with DTR/HB-EGF and up-regulates the number of functional DTRs and DT sensitivity, and that HB-EGF is identical to DTR. PMID- 8194525 TI - Ras-dependent signal transduction is indispensable but not sufficient for the activation of AP1/Jun by PKC delta. AB - Modulation of gene expression by 12-O-tetradecanoylphorbol-13-acetate (TPA) is thought to be mediated by protein kinase C (PKC), a major cellular receptor for TPA. We confirm this by showing that the overexpression of PKC delta enhances the TPA induction of the TRE-tk-CAT reporter gene in NIH3T3 cells. To investigate the mutual relationship between PKC delta- and Ras-dependent signal transduction pathways to a TRE binding transcription factor, AP1/Jun, we constructed constitutively active and dominant negative mutants of PKC delta. Activated Ras induced reporter gene expression in collaboration with overexpressed c-Jun or JunD, and this induction was insensitive to the dominant negative PKC delta. On the other hand, reporter gene expression induced by the constitutively active PKC delta was severely inhibited by dominant negative Ras, as well as by the dominant negative PKC delta. Thus, Ras activation must be indispensable for PKC delta to activate AP1/Jun. In the absence of overexpressed c-Jun or JunD, activated Ras was, however, clearly less effective than constitutively active PKC delta which showed full activation of reporter gene expression by itself. This suggests the presence of an additional, Ras-independent, signaling pathway downstream of PKC delta to activate AP1/Jun. In spite of the remarkable ability of constitutively active PKC delta to activate TRE-tk-CAT expression, this mutant suppressed cell growth. PMID- 8194526 TI - c-Abl kinase regulates the protein binding activity of c-Crk. AB - c-Crk is a proto-oncogene product composed largely of Src homology (SH) 2 and 3 domains. We have identified a kinase activity, which binds to the first Crk SH3 domain and phosphorylates c-Crk on tyrosine 221 (Y221), as c-Abl. c-Abl has a strong preference for c-Crk, when compared with common tyrosine kinase substrates. The phosphorylation of c-Crk Y221 creates a binding site for the Crk SH2 domain. Bacterially expressed c-Crk protein lacks phosphorylation on Y221 and can bind specifically to several proteins, while mammalian c-Crk, which is phosphorylated on tyrosine, remains uncomplexed. The protein binding activity of c-Crk is therefore likely regulated by a mechanism similar to that of the Src family kinases. v-Crk is truncated before c-Crk Y221 and forms constitutive complexes with c-Abl and other proteins. Our results suggest that c-Abl regulates c-Crk function and that it could be involved in v-Crk transformation. PMID- 8194527 TI - PIK1, an essential phosphatidylinositol 4-kinase associated with the yeast nucleus. AB - Transmission of mitogenic and developmental signals to intracellular targets is often mediated by inositol derivatives. Here we present the cloning and characterization of a gene from Saccharomyces cerevisiae, PIK1, encoding the enzyme that catalyses the first committed step in the production of the second messenger inositol-1,4,5-trisphosphate. PIK1 encodes a phosphatidylinositol 4 kinase (PI 4-kinase) essential for growth. Cells carrying PIK1 on a multicopy vector overexpress PI 4-kinase activity exclusively in a nuclear fraction, suggesting that PIK1 is part of a nuclear phosphoinositide cycle. Temperature sensitive mutations, but not a null mutation, can be suppressed by high osmolarity or an elevated concentration of Ca2+. Conditional mutants have a cytokinesis defect as indicated by a uniform terminal phenotype of cells with large buds and fully divided nuclei. We suggest that PIK1 controls cytokinesis through the actin cytoskeleton. PMID- 8194528 TI - The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor. AB - ERCC2 is involved in the DNA repair syndrome xeroderma pigmentosum (XP) group D and was found to copurify with the RNA polymerase II (B) transcription factor BTF2/TFIIH that possesses a bidirectional helicase activity. Antibodies directed towards the 89 kDa (ERCC3) or the p62 subunit of BTF2 are able to either immunoprecipitate ERCC2 or shift the polypeptide in a glycerol gradient. Conversely, an antibody directed towards ERCC2 also retains or shifts BTF2. ERCC2 could be resolved from the other characterized components of BTF2 upon salt treatment, while its readdition enhanced BTF2 transcription activity. ERCC2, ERCC3 and p44 are three repair proteins found in association with BTF2. Two of them, ERCC2 and ERCC3, are responsible for atypical forms of XP disorders which confer a high predisposition to skin cancer. This includes clinical features that lack an adequate rationalization on the basis of nucleotide excision repair (NER) deficiency but which may now be explained better in terms of a partial transcription deficiency. PMID- 8194529 TI - p44 and p34 subunits of the BTF2/TFIIH transcription factor have homologies with SSL1, a yeast protein involved in DNA repair. AB - The human BTF2 (TFIIH) transcription factor is a multisubunit protein involved in transcription initiation by RNA polymerase II (B) as well as in DNA repair. In addition to the previously characterized p62 and p89/ERCC3 subunits, we have cloned two other subunits of BTF2, p44 and p34. The gene encoding p44 appeared to be the human counterpart of SSL1, a gene involved in translation and UV resistance in yeast. Interestingly, the p34 subunit also has homology with a domain of SSL1, suggesting that it corresponds to an as yet unidentified protein involved in DNA repair. Both p44 and p34 possess zinc finger domains that may mediate BTF2 binding to nucleic acids. PMID- 8194530 TI - Suppression of DNA replication via Mos function during meiotic divisions in Xenopus oocytes. AB - Meiosis is characterized by the absence of DNA replication between the two successive divisions. In Xenopus eggs, the ability to replicate DNA develops during meiotic maturation, but is normally suppressed until fertilization. Here we show that development of the DNA-replicating ability depends on new protein synthesis during meiosis I, and that mere ablation of the endogenous c-mos product Mos allows maturing oocytes to enter interphase and replicate DNA just after meiosis I. Moreover, we demonstrate that during normal maturation cdc2 kinase undergoes precocious inactivation in meiosis I and then premature reactivation before meiosis II; importantly, this premature cdc2 reactivation absolutely requires Mos function and its direct inhibition by a dominant-negative cdc2 mutant also results in nuclear reformation and DNA replication immediately after meiosis I. These findings indicate that suppression of DNA replication during meiotic divisions in Xenopus oocytes is accomplished by the Mos-mediated premature reactivation of cdc2 kinase. We suggest that these mechanisms for suppressing DNA replication may be specific for meiosis in animal oocytes, and that the ultimate biological function, including the well known cytostatic factor activity, of Mos during meiotic maturation may be to prevent undesirable DNA replication or parthenogenetic activation before fertilization. PMID- 8194531 TI - The yeast telomere-binding protein RAP1 binds to and promotes the formation of DNA quadruplexes in telomeric DNA. AB - The protein RAP1 is essential for the maintenance of the telomeres of Saccharomyces cerevisiae and binds in vitro to multiple sites found within the TG1-3 telomeric repeats. We show here that, in addition to its known binding activity for double-stranded DNA, RAP1 binds sequence-specifically to the GT strands. This indicates that RAP1 is the protein that binds to the telomeric terminal GT-tails. Furthermore, we have found that RAP1 binds to and promotes the formation of G-tetrads, i.e. DNA quadruplexes, in GT-strand oligonucleotides at nanomolar concentrations. The formation of DNA quadruplexes appears to involve the intermolecular association of GT-strands. The minimal DNA-binding domain of RAP1 (DBD) binds only to double-stranded DNA, so that the novel DNA-binding activity we have found involves regions of the protein located outside of the DBD. The finding that a telomeric protein promotes the formation of G-tetrads argues for the use of DNA quadruplexes in telomere association. PMID- 8194532 TI - Functional association of essential splicing factor(s) with PRP19 in a protein complex. AB - We have previously shown that the yeast PRP19 protein is a spliceosomal component, but is not tightly associated with small nuclear RNAs. It appears to associate with the spliceosome concomitant with or just after dissociation of the U4 small nuclear RNA during spliceosome assembly. We have found that PRP19 is associated with a protein complex in the splicing extract and that at least one of the associated components is essential for splicing. Taking advantage of the epitope tagging technique, we have isolated the PRP19-associated complex by affinity chromatography. The isolated complex is functional for complementation for the heat-inactivated prp19 mutant extract, and consists of at least seven polypeptides in addition to PRP19. At least three of these can interact directly with the PRP19 protein. We also show that the PRP19 protein itself is in an oligomeric form, which might be a prerequisite for its interaction with these proteins. PMID- 8194533 TI - The site of 3' end formation of histone messenger RNA is a fixed distance from the downstream element recognized by the U7 snRNP. AB - Two conserved elements direct the 3' end processing of histone messenger RNA: a stem-loop structure immediately upstream of the site of cleavage and the histone downstream element (HDE), located 12-19 nucleotides downstream of the stem-loop in the premessenger RNA. We studied the role of these two elements by systematically inserting up to 10 C residues between them in the mouse H2A-614 histone pre-mRNA. 3' End mapping of RNAs processed in vitro demonstrated that as the HDE is move downstream, the site of cleavage correspondingly moves 3'. In addition, the efficiency of processing declines. In the wild-type substrate, cleavage occurs 3' of an A residue; modest increases in the efficiency of processing of the insertion mutants were observed when an A residue was placed at the new cleavage site. The results of psoralen cross-linking studies and immunoprecipitations using anti-trimethylguanosine antibodies indicated that the decreased processing efficiency of the insertion mutants is not due to impaired binding of the U7 small nuclear ribonucleoprotein (snRNP). We conclude that the mammalian U7 snRNP acts as a molecular ruler, targeting enzymatic components of cleave histone pre-mRNAs a fixed distance from its binding site, the HDE. PMID- 8194534 TI - RNA 3' end signals of the S.pombe ura4 gene comprise a site determining and efficiency element. AB - We have defined sequences in the 3' non-coding region of the Schizosaccharomyces pombe ura4 gene that are required for efficient mRNA 3' end formation. Three separate sequence elements have been identified. Two of these are site determining elements which specify alternative sites of polyadenylation [the major poly(A) site and a minor downstream poly(A) site]. The third sequence, located downstream of both poly(A) sites, functions as an efficiency element that enhances utilization of either polyadenylation site. By employing sensitive RT PCR analysis, we demonstrate that although low levels of transcripts are detected up to the efficiency element, none is detected beyond this point. The downstream site determining element and efficiency element have both been delineated to specific 16 nt sequences which we show are together sufficient for ura4 mRNA 3' end formation. We have further characterized the interaction between these two elements and show that the efficiency element behaves in a position-independent, orientation-dependent manner, but cannot form 3' ends independently of the site determining element. Surprisingly, we find that the efficiency element can be functionally replaced by a second copy of either site determining element. We present a model for the mechanism of RNA 3' end formation of the ura4 gene and note that this bipartite structure for a poly(A) signal in S.pombe may be related to the AAUAAA and downstream GU-rich sequences of poly(A) signals in mammalian genes. PMID- 8194535 TI - Many of the conserved nucleotides of tRNA(Phe) are not essential for ternary complex formation and peptide elongation. AB - An RNase protection assay was used to show that the dissociation rate constants and equilibrium constants of unmodified yeast and Escherichia coli phenylalanyl tRNA(Phes) to elongation factor Tu from E.coli were very similar to each other and to their fully modified counterparts. The affinity of aminoacylated tRNA to elongation factor Tu was substantially lower when GTP analogues were used in place of GTP, emphasizing the importance of the beta-gamma phosphate linkage in the function of G-proteins. Fourteen different mutations in conserved and semi conserved nucleotides of yeast phenylalanyl-tRNA(Phe) were tested for binding to elongation factor Tu.GTP and assayed for activity in the ribosomal A- and P sites. Most of the mutations did not severely impair the function of these tRNAs in any of the assays. This suggests that the translational machinery does not form sequence-specific interactions with the conserved nucleotides of tRNA. PMID- 8194536 TI - A mutant cysteinyl-tRNA synthetase affecting timing of chromosomal replication initiation in B. subtilis and conferring resistance to a protein kinase C inhibitor. AB - A Bacillus subtilis mutant spnA95 was isolated as resistant at 30 degrees C to the protein kinase C (PKC) inhibitor, sphinganine, and temperature sensitive for growth. As deduced by flow cytometry measurements, the mutant has a 35% reduced initiation mass at permissive temperature, resulting in initiation of DNA replication much earlier in the cell cycle than in the wild type. This modification is accompanied by a change in cell size, as determined by phase contrast microscopy and flow cytometry. Therefore, this strain displays the characteristics of a novel cell clock mutant. spnA is a newly identified gene in B.subtilis and was shown to encode a cysteinyl-tRNA synthetase. At non-permissive temperature, the mutant was defective in the synthesis of P70, a protein with several characteristics of PKC (a cysteine-rich protein). As one possibility, we propose that the altered timing of replication may be due to the reduced synthesis of specific cysteine-rich proteins normally involved in controlling chromosomal replication initiation in B. subtilis. PMID- 8194537 TI - Standardisation of 31phosphorus-nuclear magnetic resonance spectroscopy determinations of high energy phosphates in humans. AB - A procedure is described for standardising the determination of adenosine 5' triphosphate and phosphocreatine concentration ([ATP] and [PC], respectively, in absolute arbitrary units) in human muscle by nuclear magnetic resonance (NMR) spectroscopy. The individual 31phosphorus (31P)-NMR spectra obtained on equal hemispherical tissue volumes (muscle plus skin and fat) were corrected for the thickness of the skin and of the subcutaneous fat. The volumes investigated were standardised using an external reference. The procedure described made possible the comparison of high energy phosphate concentrations among different subjects. It was applied to the assessment of [ATP] and [PC] in four groups of sedentary subjects (children, and adults aged 20-35, 35-50 and over 50 years), and in a group of athletes (volleyball players). The [ATP] and [PC] were not statistically different in the groups investigated. PMID- 8194538 TI - Determinants of peak muscle power: effects of age and physical conditioning. AB - The relationships between absolute peak muscle power (Wpeak), muscle cross sectional area (CSAtot, i.e. the sum of both thigh and calf CSA) and muscle high energy phosphate concentration (adenosine 5'-triphosphate [ATP] and phosphocreatine concentrations [PC]) were studied in 47 subjects classified into five groups: A, 10 sedentary (S) subjects aged 20-35 years; B, 9 S aged 35-50 years; C, 9 S aged more than 50 years; D, 13 children aged 8-13 years; and E, 6 athletes (top level volleyball players) aged 24 (SD 3) years. The Wpeak was measured during a maximal vertical high jump off both feet on a force platform. The CSAtot was measured anthropometrically. The [ATP] and [PC] were determined by 31Phosphorus nuclear magnetic resonance spectroscopy. The Wpeak decreased with age, was 65% lower in D than in A, and 43% higher in E than in A. The CSAtot did not vary with age, was 45% smaller in D than in A, and 15% greater in E than in A. The [ATP] and [PC] were essentially the same in all groups. The changes observed in Wpeak were only partially accounted for by changes in CSAtot. Therefore, in addition to the variables investigated, other factors appear to have been involved in the determination of Wpeak with increasing age and training. An important role may be played by hormonal, particularly at puberty, and neural factors. PMID- 8194539 TI - Local sweating responses during recovery sleep after sleep deprivation in humans. AB - Changes in the central control of sweating were investigated in five sleep deprived subjects (kept awake for 40 h) during their recovery sleep under warm ambient conditions [operative temperature (T(o)) was either 35 or 38 degrees C]. Oesophageal (T(oes)) and mean skin (Tsk) temperatures, chest sweat rate (msw,ch), and concomitant electro-encephalographic data were recorded. Throughout the night at 35 or 38 degrees C T(o), msw,ch changes were measured at a constant local chest skin temperature (Tch) of 35.5 degrees C. The results showed that body temperatures (T(oes) and Tsk) of sleep-deprived subjects were influenced by thermal and hypnogogic conditions. The msw,ch levels correlated positively with T(oes) in the subjects studied during sleep stage 1-2 (light sleep: LS), sleep stage 3-4 (slow wave sleep: SWS) and rapid eye movement (REM) sleep. Contrary to what has been reported in normal sleep, firstly, the T(oes) threshold for sweating onset differed between REM sleep and both LS and SWS, and, secondly, the slopes of the msw,ch versus T(oes) relationships were unchanged between REM and non-REM (i.e. LS or SWS) sleep. The changes observed after sleep deprivation were hypothesized to be due to alterations in the functioning of the central nervous system controller. PMID- 8194540 TI - Atrial natriuretic peptide in plasma after prolonged physical strain, energy deficiency and sleep deprivation. AB - Plasma concentrations of atrial natriuretic peptide (ANP) were investigated daily in 16 male cadets during a 6-day military training course with continuous heavy physical activities, sleep and energy deficiency (course I). At the end of another similar course (course II) 15 cadets were studied during 30-min cycle exercise at 50% maximal oxygen uptake with and without glucose infusion. A small, but not significant increase was found in the plasma concentrations of ANP during course I from 9.6 (SEM 1.1) pmol.l-1 in the control experiment to 11.1 (SEM 0.5) pmol.l-1 on day 5. During course II a small but significant increase was found from 7.8 (SEM 0.5) pmol.l-1 in the control experiment to 9.1 (SEM 0.5) pmol.l-1 at the end of the course. Plasma osmolality and chloride concentration decreased during the course. During the exercise test a significant increase was seen in ANP concentration from 8.2 (SEM 0.8) to 13.1 (SEM 2.0) pmol.l-1 in the control experiment and from 9.4 (SEM 0.7) to 13.5 (SEM 1.2) pmol.l-1 during the course. This response was attenuated by glucose infusion, an effect which may have been due to an exercise induced increase in plasma chloride concentration being abolished. In contrast, the potassium concentration response to exercise was increased during the course but unaffected by glucose infusion. In conclusion, the large increases in endogenous plasma catecholamine concentration shown to take place during previous courses were not reflected in the plasma concentrations of ANP, indicating only a moderate cardiac stress or no cardiac work overload during such courses. PMID- 8194541 TI - Comparison of haemodynamic effects during venous air infusion and after decompression in pigs. AB - We have compared haemodynamic effects of venous gas emboli during continuous air infusion into the right atrium and after rapid decompression in pigs. Eight anaesthetized and spontaneously breathing pigs received continuous air infusion at a rate of either 0.05 ml.kg-1.min-1 (six pigs, air infusion group) or 0.10 ml.kg-1.min-1 (two pigs). Another eight pigs (decompression group) underwent a 30 min compression to 5 bar (500 kPa, absolute pressure), followed by a rapid decompression (2 bar.min-1). Haemodynamic variables were measured or calculated, and bubbles in the pulmonary artery were monitored using transoesophageal echocardiography. The results showed less variation in the maximal increase in mean pulmonary arterial pressure (BPa,pulm) during air infusion (0.05 ml.kg-1.min 1) than after decompression, although the mean maximal increase did not differ between the two groups [28.0 mmHg (3.73 kPa), 95% confidence interval (CI) 23.5 32.5, vs 32.0 mmHg (4.27 kPa), 95% CI 25.3-38.7, P = 0.3]. The BPa,pulm stabilized or decreased very slowly after peak values were reached in the air infusion group, whereas the BPa,pulm decreased rapidly during the same period in the decompression group. No significant changes in mean arterial pressure were observed during air infusion (0.05 ml.kg-1.min-1), in contrast to the rapid increase and the subsequent decrease, that appeared after decompression. Finally, the maximal bubble count was much lower in the air infusion group than in most of the pigs in the decompression group. The two pigs that received 0.10 ml.kg-1.min 1 stopped breathing after 5-min infusion, developed arterial hypotension and died. PMID- 8194542 TI - Digital and brachial artery blood pressure measurements during peripheral, cold induced vasoconstriction. AB - Measurements of digital artery blood pressure made using an automated photoplethysmographic method (Finapres), in the middle finger of the left hands of nine male subjects, were compared with pressure measures in the right brachial artery using a method relying on the abolition of Karotkoff sounds during occlusion of the upper arm by a pressure cuff (Dinamap), during a 40-min immersion of the hand in cold (4 degrees C) and thermoneutral (32 degrees C) water. Blood flow in the left index finger was assessed and temperatures of the left and right ring fingers were also measured. Before immersion, systolic pressures in the digital artery were higher than systolic pressures in the brachial artery (P < 0.05), whereas the corresponding diastolic measurements were similar. However, both systolic (P < 0.01) and diastolic (P < 0.05) digital artery measurements increased with time. During cold immersion both systolic and diastolic pressures increased at both sites (P < 0.01), although the digital artery systolic readings rose sharply and then declined, whereas the brachial artery readings were stable. The cold-immersed digital artery diastolic measurements were greater than the brachial artery measurements (P < 0.01) and showed a continuation of the upward trend noted prior to immersion (P < 0.01). Thermoneutral diastolic digital artery measurements also showed this continued trend (P < 0.001). Some individual photoplethysmograph assessments of index finger blood flows showed intermittent vasodilatation, but cold immersion caused a decline in mean flow to 22% of pre-immersion value at 15 min, followed by an increase to 40%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194543 TI - Specific tension of elbow flexor and extensor muscles based on magnetic resonance imaging. AB - Series cross-section images of the upper extremity were obtained for four men by magnetic resonance imaging (MRI) and anatomical cross-sectional areas (ACSA) of elbow flexor muscles [biceps brachii (BIC), brachialis (BRA), brachioradialis (BRD)] and extensor muscles [triceps brachii (TRI)] were measured. Physiological cross-sectional area (PCSA) was calculated from the muscle volume and muscle fibre length, the former from the series ACSA and the latter from the muscle length multiplied by previously reported fibre/muscle length ratios. Elbow flexion/extension torque was measured using an isokinetic dynamometer and the force at the tendons was calculated from the torque and moment arms of muscles measured by MRI. Maximal ACSA of TRI was comparable to that of total flexors, while PCSA of TRI was greater by 1.9 times. Within flexors, BRA had the greatest contribution to torque (47%), followed by BIC (34%) and BRD (19%). Specific tension related to the estimated velocity of muscle fibres were similar for elbow flexors and extensors, suggesting that the capacity of tension development is analogous between two muscle groups. PMID- 8194544 TI - Comparison of muscle cross-sectional area and strength between untrained women and men. AB - The cross-sectional areas (CSA) of fat, muscle and bone tissues of the limb as well as maximal voluntary isokinetic strength were measured in untrained men (n = 27) and women (n = 26) aged 18-25 years. Anatomical CSA of the three tissues were determined by ultrasound on the upper arm and thigh. The isokinetic strength of the elbow and knee extensor and flexor muscles were measured by an isokinetic dynamometer (Cybex II) at 1.05 rad.s-1. The women had significantly (P < 0.001) larger fat CSA and smaller bone and muscle CSA than the men in both the upper arm and thigh. Among tissue CSA, the largest difference between the women and men was found in fat CSA regardless of the measurement sites. The sex differences in bone and muscle CSA were found largely in the upper arm compared to the thigh, even when expressed per unit second power of the limb length. Regression analyses of the data for respective samples for the men and women showed significant correlations (r = 0.411-0.707, P < 0.05-P < 0.001) between CSA and strength in all muscle groups except for the elbow extensors of the men (r = 0.328, P > 0.05) and the elbow flexors of the women (r = 0.388, P > 0.05). No significant difference between sexes was observed when strength was expressed per unit of muscle CSA (F.CSA-1) for the elbow flexors and extensors. However, the men showed significantly higher F.CSA-1 than the women for the knee flexors and extensors (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194545 TI - Maximal oxygen uptake, anaerobic threshold and running economy in women and men with similar performances level in marathons. AB - Sex differences in running economy (gross oxygen cost of running, CR), maximal oxygen uptake (VO2max), anaerobic threshold (Th(an)), percentage utilization of aerobic power (% VO2max), and Th(an) during running were investigated. There were six men and six women aged 20-30 years with a performance time of 2 h 40 min over the marathon distance. The VO2max, Th(an), and CR were measured during controlled running on a treadmill at 1 degree and 3 degrees gradient. From each subject's recorded time of running in the marathon, the average speed (vM) was calculated and maintained during the treadmill running for 11 min. The VO2max was inversely related to body mass (mb), there were no sex differences, and the mean values of the reduced exponent were 0.65 for women and 0.81 for men. These results indicate that for running the unit ml.kg-0.75.min-1 is convenient when comparing individuals with different mb. The VO2max was about 10% (23 ml.kg-0.75.min-1) higher in the men than in the women. The women had on the average 10-12 ml.kg 0.75.min-1 lower VO2 than the men when running at comparable velocities. Disregarding sex, the mean value of CR was 0.211 (SEM 0.005) ml.kg-1.m-1 (resting included), and was independent of treadmill speed. No sex differences in Th(an) expressed as % VO2max or percentage maximal heart rate were found, but Th(an) expressed as VO2 in ml.kg-0.75.min-1 was significantly higher in the men compared to the women. The percentage utilization of fcmax and concentration of blood lactate at vM was higher for the female runners.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194546 TI - The role of central command in ventilatory control during static exercise. AB - The role of central command in the respiratory response to 15 min of rhythmic static (isometric) exercise was studied in humans. Voluntary exercise (VE) was compared with electrically induced exercise (EE) at three different work intensities, i.e. 5%, 15% and 25% of maximal voluntary contraction. A group of 12 volunteers participated in the study and each of them performed six sessions. A session consisted of at least 5 min rest, 15 min rhythmic-static single leg exercise (4 s contraction/12 s relaxation) and at least 5 min recovery. Force, minute ventilation (VE) and oxygen uptake (VO2) were measured. In EE, both VE and VO2 increased continuously during the entire exercise period after an initial rapid increase at all three work intensities. Correlation between VE and VO2 was highly significant during EE. During all three work intensities of VE, VE and VO2 achieved a steady-state after the initial increase. During VE, VE did not correlate as closely with VO2 as during EE. All these findings indicate that central command was not imperative for an adequate ventilatory response to exercise within all three work intensities investigated. Without the influence of central command, correlation between VE and VO2 was even better than during VE. PMID- 8194547 TI - Disturbance of thermal homeostasis during post-exercise hyperthermia. AB - The response of core temperature to exercise was investigated during recovery in order to avoid the antagonistic competition between exercise and thermal reflexes for the same effector systems which control skin blood flow. Five healthy, non training males [mean (SD) age, 23.8 (2.04) years] were habituated to 29 degrees C at relative 50% humidity for more than 2 h and then exercised by treadmill running at about 75% maximum oxygen uptake for 18 min. They then remained at 29 degrees C for up to 65 min of recovery. Oesophageal (T(es)), rectal (Tre) and skin temperatures (Tsk) were recorded at 5-s intervals throughout. The abrupt fall of temperature gradient from the forearm to finger was used to identify the T(es) for skin vessel dilatation (Tdil) during exercise. Mean (SE) Tes rose from a resting value of 36.67 (0.15) degrees C to 38.22 (0.24) degrees C, mean Tre rose from 37.09 (0.25) degrees C to 38.23 (0.15) degrees C, and Tdil occurred at 37.39 (0.32) degrees C. Within 10 min of recovery mean T(es) fell to 37.31 (0.24) degrees C, where it remained a significant 0.64 degrees C above its pre-exercise (PrEx) level (P < or = 0.018) but insignificantly different from Tdil for the remaining 55 min of recovery. Meanwhile, Tre fell gradually throughout recovery to 37.64 (0.18) degrees C. The Tsk at all non-acral sites except the thigh had recovered to PrEx levels by 20-30 min post-exercise (PoEx).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194548 TI - Measurement of directional force and power during human submaximal and maximal isokinetic exercise. AB - An isokinetic cycle ergometer has been developed to measure power output generated over a wide range of constant velocities. The ergometer system has two operating modes and it can be instantly switched from one to another. In its conventional mode the cycle ergometer is connected to a conventional electrically braked cycle ergometer so that the subjects can perform submaximal steady-state exercise. For maximal power measurements the system can be instantly switched to an isokinetic control mechanism which allows a constant pedalling rate to be set in the range of 23-180 rev.min-1. In both operating modes the forces generated on the pedals are monitored by strain-gauges mounted inside the pedals. This enables information to be obtained regarding the direction of forces generated at the foot-pedal interface. The output from the strain-gauges was A-D converted and stored along with data giving pedal and crank position. Data was sampled 150 times in each revolution of the crank. Force data are usually analysed for maximal peak power (highest instantaneous power generated during each revolution), mean power (power generated over a complete revolution), extension and flexion power (power generated during leg extension and leg flexion respectively). This system allows characterisation of the relationship between maximal leg power and pedalling rate, both under control and exercise-induced potentiation and fatigue conditions. Thus it is possible for example to quantify instantly the magnitude of fatigue induced by preceding dynamic exercise of a given duration, intensity or contraction velocity. PMID- 8194549 TI - The use of critical power as a determinant for establishing the onset of blood lactate accumulation. AB - Eight highly trained male kayakers were studied to determine the relationship between critical power (CP) and the onset of blood lactate accumulation (OBLA). Four exercise sessions of 90 s, 240 s, 600 s, and 1200 s were used to identify the CP of each kayaker. Each individual CP was obtained from the line of best fit (LBFCP) obtained from the progressive work output/time relationships. The OBLA was identified by the 4 mmol.l-1 blood lactate concentration and the work output at this level was determined using a lactate curve test. This consisted of paddling at 50 W for 5 min after which a 1-min rest was taken during which a 25 microliters blood sample was taken to analyse for lactate. Exercise was increased by 50 W every 5 min until exhaustion, with the blood sample being taken in the 1 min rest period. The exercise intensity at the OBLA for each subject was then calculated and this was compared to the exercise intensity at the LBFCP. The intensity at LBFCP was found to be significantly higher (t = 2.115, P < 0.05) than that at the OBLA of 4 mmol.l-1. These results were further confirmed by significant differences being obtained in blood lactate concentration (t = 8.063, P < 0.05) and heart rate values (t = 2.90, P < 0.05) obtained from the exercise intensity at LBFCP over a 20-min period and that of the anaerobic threshold (Th(an)) parameters obtained from the lactate/heart rate curve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194550 TI - Sidney Farber (1903-1973). PMID- 8194551 TI - Bone marrow cytological storage phenomena in lipidoses. AB - The bone marrow cytological storage phenomena in generalized lysosomal lipid storage disorders (Gaucher disease, Niemann-Pick disease, GM1-gangliosidosis, cholesterol ester storage diseases) are reviewed. The value of bone marrow cytology as a pre-screening method in the diagnostic strategy for the different diseases depends on the disease type suspected and the availability of biochemical screening methods. While cytological screening is not necessary in certain patients with typical clinical pictures, it may prove undispensable in others. PMID- 8194552 TI - Hypothesis: myopia of prematurity is caused by postnatal bone mineral deficiency. AB - Myopia is a frequent finding in preterm children. The close association between myopia and retinopathy of prematurity (ROP) suggested a causal relationship, but myopia of prematurity without ROP has yet to be explained. An alternative explanation is presented: myopia is caused by postnatal ellipsoid deformation of the spheric eyeball, i.e. excessive elongation of the optical, as a result of a dolichocephalic deformation of the skull with a short frontal axis. This deformation of the skull is the direct result of bone mineral deficiency frequently observed in very low birth weight infants with increasing postnatal age. This hypothesis is supported by the results of a historical comparison of very low birth weight infants without and with supplementation with calcium and phosphorus that was given in order to prevent postnatal bone mineral deficiency. In the unsupplemented group 4 of 23 children (61%) needed spectacles but only 6 out of 55 (11%) children who were supplemented as babies (questionnaire). Refraction measurements showed myopia stronger than -1 o.d. in group 1 in 5 of 14 infants, whereas in group 2 only 2 out of 22 infants were myopic (P < 0.05). PMID- 8194553 TI - The effect of oestrogen treatment on body proportions in constitutionally tall girls. AB - Body proportions were studied in 31 girls with constitutional tall stature during treatment with 200 micrograms ethinyl oestradiol per day continuously, combined with 5-10 mg medroxyprogesterone on the first 10 days of each month. Their mean (+/- SD) predicted adult height was 186.0 (+/- 4.0) cm. At the start of therapy, leg length (LL) standard deviation score (SDS) (3.8 +/- 0.7) was significantly greater than the sitting height (SH) SDS (2.3 +/- 1.1). During therapy, the mean sitting height increased by 2.9 cm, in contrast to an increment of only 0.8 cm for LL. The SDS of the ratio between SH and LL remained below zero. The expected gain without therapy, assuming a stable SDS position over time, was 5.4 cm for SH and 4.4 cm for LL, significantly more than the observed gains. In conclusion, tall girls have relatively long legs. Oestrogen therapy leads to an almost complete stop of leg growth, while the growth of the trunk is reduced to a lesser extent. This selective inhibition results in a trunk/leg ratio which is closer to, though still significantly different from that of normal girls. PMID- 8194554 TI - Familial testotoxicosis in a Chinese family. AB - We report two cases of 'familial testotoxicosis' in a family of Southern Chinese descent. The proband, an 8-year 4-month-old boy and his 35-year-old father both presented with early sexual development. In both cases the testicular volume was only 6 ml despite fully developed secondary sexual characteristics. Both patients had adult testosterone concentrations but a suppressed gonadotrophin response to gonadotrophin-releasing hormone. The suppressed gonadotrophin response to gonadotrophin-releasing hormone in the father suggests that autonomous gonadal production of sex steroid by the testes can persist well into adult life in some patients with familial testotoxicosis. PMID- 8194555 TI - Diagnosis of X-recessive Kallmann syndrome in early infancy. Evidence of hypoplastic rhinencephalon. AB - A 3-month-old infant presented with hypogonadism, a small penis and bilateral cryptorchidism. He showed an insufficient response of luteotropic hormone (LH) and follicle stimulating hormone (FSH) to luteotropic hormone releasing hormone (LHRH) and of testosterone to human chorionic gonadotropin. The maternal uncle had hypogonadism and anosmia and also showed an impaired LH and FSH response to LHRH. MRI examination showed hypoplasia of the rhinencephalon in both cases. These findings in the son and brother of the clinically unaffected mother suggest X-linked recessive inheritance. PMID- 8194556 TI - Risks and benefits of antireflux operations in neurologically impaired children. AB - Gastro-oesophageal reflux (GER) in neurologically impaired children often causes feeding problems and complications of oesophagitis and is frequently resistant to medical treatment. Fifty neurologically impaired children underwent anterior gastropexy as anti-reflux operation, combined with gastrostomy in 23, between 1976 and 1992. There was no operative mortality. There were 25 early complications in 14 patients and 9 late complications in 9 patients. Twelve patients needed 17 re-operations for delayed gastric emptying [4], intestinal obstruction [3], para-oesophageal hernia [3], oesophageal stenosis [4], and recurrent GER, revision of gastrostomy, subphrenic abscess (one each). Nine patients died during the follow up period. Death in two children was related to the operation (incarcerated para-oesophageal hernia and blow-out of the stomach). Out of 41 survivors, the operation was judged successful in 35. It is concluded that antireflux operations in neurologically impaired children carry a high risk of complications. Preoperative identification of risk factors is not possible. The improvements in the quality of life achieved in the majority of patients outweigh the risks. PMID- 8194557 TI - The determination of ultrasound velocity in the os calcis, thumb and patella during childhood. AB - Maximising the accumulation of bone tissue during growth and puberty is one of the most important aims in the prevention of osteoporosis. For prevention studies in children it is necessary to develop methods for skeletal status without radiation. Ultrasonic velocity (speed of sound = SOS) has been proposed as an alternative method. Using a new ultrasonic system (Osteoson K4, Minhorst, Germany), we investigated the reproducibility and age-dependency of SOS in several peripheral bones in 218 children and young adults. Intra-observer (day to day) reproducibility: calcaneus CV = 0.64%, patella CV = 1.18% and thumb CV = 0.43% (n = 25). Inter-observer reproducibility: calcaneus CV = 1.1%, patella CV = 2.48% and thumb CV = 0.62% (n = 16). SOS in thumb and patella increased with age and peaked at 20-25 years. SOS in the calcaneus showed no increase after puberty. Studies in bones from pigs show no dependency of SOS from the thickness of analysed cortical or trabecular bone slices. We conclude that the reproducibility of SOS measurements especially in the thumb is comparable with those of radiation methods. The SOS data in growing, healthy children and the independency from bone dimensions provides more evidence that SOS describes the elastic qualities of the bones. PMID- 8194559 TI - Intelligence in mild atypical phenylketonuria. AB - In 82 children with mild phenylketonuria (PKU) (blood phenylalanine (Phe) concentrations consistently below 900 mumol/l throughout follow up) the relationship between intelligence at age 4 (IQ by Stanford-Binet) and average blood Phe concentrations from birth to 4 years was examined. Of the 82 children 24 had received no treatment. In the group as a whole, and in the 24 untreated subjects alone, mean IQs were significantly below population norms, with deficits of approximately 4.5 points and 9 points respectively. After allowing for social class IQ fell progressively by approximately 6 points for each 100 mumol/l rise in mean Phe concentrations in both the treated and untreated subjects. This relationship resembled that previously reported in early treated children with more severe forms of PKU, except that the scale of the relationship was even greater. We conclude that all children whose blood Phe concentrations reach 400 mumol/l or above should receive a low Phe diet, at least during the preschool years, and that the aim should be to control blood Phe levels below 400 mumol/l throughout early childhood in all forms of PKU. PMID- 8194558 TI - Distribution of lymphocyte surface antigens in healthy neonates. AB - Using flow cytometric analysis we investigated the distribution of major lymphocyte surface antigens in newborn infants. A total of 221 newborns entered the study, of whom 53 fulfilled our criteria of healthy mature neonates. Percentages of immunofluorescent-positive cells were as follows (median and range from 25th to 75th percentiles given): for CD1 3.8%; 2.3%-5.8%. CD2 60.9%; 52.4% 66.8%. CD3 57.5%; 50.5%-63.3%. TcRass 57.7%; 48.1%-60.0%. CD4 36.3%; 28.0%-42.6%. CD8 23.0%; 20.0%-27.4%. CD11a 56.3%; 46.3%-68.5%. CD19 12.1%; 8.6%-14.8%. CD20 10.9%; 8.4%-12.9%. CD25 2.6%; 2.1%-4.5%. CDw52 61.0%; 51.2%-76.1%. CD71 5.2%; 3.1%-9.3%. While the ranges for the percentage of immunofluorescent-positive cells were rather small, there was a wide variation in the absolute numbers of marker immunofluorescent-positive cells. PMID- 8194560 TI - Rett syndrome in a patient with medium chain acyl-CoA dehydrogenase deficiency. AB - A female patient with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency developed normally until 13 months of age after which she showed a gradual developmental delay, followed by progressive dementia, and a decrease in head circumference growth culminating in the diagnosis of Rett syndrome at 3.5 years. PMID- 8194561 TI - Absence of cytochrome c oxidase activity in a boy with dysfunction of renal tubules, brain and muscle. AB - We report on a boy who developed proximal renal tubular acidosis with loss of carnitine at the age of about 6 months. A few months later he began to suffer from progressive muscular weakness and neurological disturbances. Blood biochemistry showed elevated lactate and beta-hydroxybutyrate with increased lactate/pyruvate and beta-hydroxybutyrate/acetoacetate ratios. A high urinary excretion of lactate and citric acid cycle intermediates was found. These results indicated a defect of the mitochondrial respiratory chain. Analysis of biopsy material from skeletal muscle revealed low activities of all respiratory chain complexes. In muscle and fibroblasts cytochrome c-oxidase (complex IV) was absent. Despite high dose multi-vitamin therapy the boy died at the age of 30 months from central respiratory failure. At autopsy the neuropathological diagnosis of Leigh disease was made. PMID- 8194562 TI - Incidence and morbidity of infection by hepatitis C virus in children with acute lymphoblastic leukaemia. AB - A group of 90 patients with acute lymphoblastic leukaemia (ALL) in first continuous complete remission (CCR), admitted in our hospital between January 1986 and September 1992, were tested for the presence of antibodies against hepatitis C virus (HCV), antibodies against hepatitis B virus and antibodies against HIV-1 during maintenance therapy or thereafter. They were compared with a group of 71 children with other malignancies in first CCR who had been diagnosed consecutively from January 1986 to September 1992. No patient with ALL or any other malignancy was found to be positive for hepatitis B surface antigen or HIV 1. HCV-specific antibodies were detected in 28 out of 87 children (32.1%) with ALL and in 4 out of 44 patients (9%) with malignancies other than ALL who had received at least one transfusion of blood or platelets (P < 0.01). HCV-specific antibodies were also detected in one out of three untransfused children with ALL but in none of the untransfused children with malignancies other than ALL. HCV specific seropositivity influenced the management of children with ALL during maintenance therapy. In fact, as a result of abnormal liver function tests, maintenance therapy had to be suspended significantly more often in the case of HCV-seropositive patients with ALL than in HCV-seronegative ones. Despite the high morbidity during maintenance therapy, chronic liver disease (CLD) was uncommon in both groups: five children with ALL (17.2% of HCV-seropositive children) and one child with a malignancy other than ALL (25%) had CLD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194563 TI - Neonatal teratoma presenting as hygroma colli. AB - We describe a neonate with a large tumour involving cranial, cervical and upper mediastinal regions, which presented clinically as hygroma colli. Radiological and pathological investigations showed characteristics of a mature teratoma and prominent cystic components within the tumour. These findings suggest that during early fetal development primary lymphatic sacs were obstructed by a teratoma leading to hygromatous dilatations of lymphatic vessels or that the abnormal proliferation of lymphatic vessels (hygroma) was part of the teratoma, developing from mesoderm as one of the three germinal layers from which teratomas originate. A third possibility is that the cystic part of the tumour originated from plexus chorioideus tissue, containing CSF. The last possibility is most probable in this patient. PMID- 8194564 TI - Time of the first defaecation and urination in very low birth weight infants. AB - The time for passage of the first stool and urine was studied in 111 infants who weighed less than 1500 g at birth. Delayed passage of the first stool (greater than 24 h) was noted in 25 (22.5%) infants of this group, including 7 cases (6.3%) in whom the delay was greater than 48 h (4 on the 3rd day, 2 on the 4th day, 1 on the 6th day of life, respectively). Three (2.7%) cases had delayed passage of the first urine (at 25, 25, and 45 h of life, respectively). Significant differences between the two groups with delayed and nondelayed passage of the first stool were noted in both the gestational age and in the time of the first enteral feeding. In very low birth weight infants, delay in the passage of the first stool is a common occurrence. This delay is probably due to physiological immaturity of the motor mechanisms of the gut, and lack of triggering effect of enteral feeds on gut hormones. As far as passage of the first urine was concerned, there were no significant perinatal factors found between the delayed and nondelayed groups. PMID- 8194565 TI - Influence of upright activity on plasma renin activity and aldosterone concentration in children. AB - Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in 156 healthy infants and children under basal conditions of normal diet and recumbency. PRA and PAC were also evaluated during and after stimulation of the renin-angiotension-aldosterone system by postural change. Basal values of PRA significantly declined with increasing age. Postural change by standing up resulted in an increase of PRA and PAC in all age groups. The increment of PRA but not of PAC was greater in older than in younger children. Neither the basal nor the stimulated levels of PRA and PAC were influenced by sex, body weight, body surface area, serum sodium, serum potassium, creatinine, and 24-h urine secretion of sodium and potassium. Both PRA and PAC returned to the basal levels within 60 min after resuming recumbent posture. PMID- 8194566 TI - Is partial deletion of the complement C4 genes associated with sudden infant death? AB - The two C4 loci C4A and C4B in 61 cases of sudden infant death (SID), 93 living controls and 7 cases of infectious death were studied. In the SID group 13.1% showed deletion of the C4A gene, while 2.5% of the cases showed deletion of the C4B gene. This was not significantly different from neither the controls nor the infectious death group. We were not able to confirm that deletion of the C4B gene is associated with SID. However, in the SID group deletion of either the C4A or the C4B gene was associated with signs of infections prior to death (P = 0.035). This observation may indicate that a proportion of SID victims are more vulnerable to infections than other infants. PMID- 8194567 TI - Tracheostomy in children. AB - We reviewed the records of 108 patients who had a tracheostomy performed over a 10-year period from July 1979 to April 1989. Median age at tracheostomy was 6 months (1 week-15 years). Indications for surgery were acquired subglottic stenosis (31.4%), bilateral vocal cord paralysis (22.2%), congenital airway malformations (22.2%) and tumours (11.1%). No epiglottis and no emergency situation had to be managed by tracheostomy. Operation was uneventful in all, but 8 patients (7.4%) developed a pneumothorax in the postoperative period. Twenty one (19.5%) had severe complications during the cannulation period (tube obstruction in 11 patients with cardiorespiratory arrest in 4; dislocation of the tube in 6 patients). Fifteen patients (13.8%) had severe complications after decannulation (2 had a cardiorespiratory arrest); all 15 had to be recannulated. At the end of the study period 85 patients (78.7%) were successfully decannulated with a median period of tracheostomy of 486 days (8 days-6.6 years). The median hospital stay was 159 days (13 days-2.7 years). All patients could be discharged. Eight patients (7.4%) died but no death was related to tracheostomy. In summary the mortality rate is lower than reported in previous reviews and tracheostomy is a safe operation even in small children but cannula-related complications may lead to life-threatening events. The management of tracheostomized small children and infants in a highly staffed and monitored intensive care unit has allowed better handling of complications and has resulted in a reduction in cannula related deaths. PMID- 8194568 TI - Spontaneous pneumothorax and mitral valve prolapse. PMID- 8194569 TI - EEC syndrome with diabetes insipidus and hypogonadism. PMID- 8194570 TI - Visceral leishmaniasis in a child with HIV-1 infection. PMID- 8194571 TI - Blood pressure in low birth weight infants after dexamethasone. PMID- 8194572 TI - Optimizing the visibility of displays for older observers. AB - Aging is associated with a variety of decremental visual changes, including reductions in retinal illuminance, color discrimination, static and dynamic acuity, near focus, contrast sensitivity, smooth and saccadic eye movements, visual field, visual search, and the ability to see in and recover from glare. Laboratory research, field studies, and self-report data all indicate that many older persons experience significant difficulty in carrying out tasks that depend on these visual functions. It is also increasingly clear that older observer's performance in finding, extracting, and using visual information can be enhanced significantly by designing task environments to minimize the effects of visual deficits. Recent research indicates that optical simulation of visual loss and contrast sensitivity testing, used in conjunction with image processing, may be very powerful tools for designing displays for the elderly and others with diminished spatial vision. These developments are reviewed, and general guidelines for creating ergonomically correct visual task environments for older observers are offered. PMID- 8194573 TI - Giving the older driver enough perception-reaction time. AB - Many types of behavior slow with age, and older drivers require more time to process information and make decisions. How greater response time requirements relate to the design of the highway environment and to features of new in-vehicle technologies is discussed. The design requirements for many different aspects of roadway geometrics and traffic control devices are based on design driver perception-reaction times. However, without knowing how much slower older drivers are than the design driver, it is difficult to determine whether they are adequately protected by current design practice and, if not, what the desired change in design should be. Attempts to address this have been hampered by the lack of directly relevant data, the situation-specific nature of certain findings, and the older driver's ability to compensate for declines in basic skills. Also discussed are the promise and problems of new in-vehicle technologies for providing the older driver with adequate time to act. These intelligent vehicle highway systems (IVHS) may speed navigational decision making and recognition of hazards and maneuver requirements. However, the possibility for interfering with quick responding also arises, and IVHS systems might disadvantage the older driver in other ways. PMID- 8194574 TI - High-priority research and development needs for maintaining the safety and mobility of older drivers. AB - The increase in the number of older drivers has resulted, in the last two decades, in a series of conferences and workshops that have outlined the magnitude of the "older driver problem." More than 150 research and development recommendations generated by these conferences were rated by a task force of the Transportation Research Board in terms of their relative importance. On the basis of this rating, six major categories of high-priority research and development needs were identified: highway design, vehicle design, licensing and rehabilitation, vision and visual assessment, biomedical issues, and general issues. The current status of research in each of the categories is reviewed, and the most important avenues for future inquiry are outlined. PMID- 8194575 TI - Age-related changes in perceptual and psychomotor performance: implications for engineering design. AB - Increased age is associated with declines in perceptual and psychomotor performance. We review several surveys of health and disability that provide functional descriptions on population trends in vision, hearing, fitness, mobility, and agility that complement laboratory studies of perceptual threshold functions. Women report and exhibit significantly greater disability than men (the exceptions being disabilities associated with hearing and flexibility), with the disability progression accelerating with age. For the growing proportion of older adults in the labor force, visual improvements can be achieved through improved lighting, increased size of visual detail, and glare avoidance. For hearing, restricting the frequency of sounds to the 1000- to 2000-Hz range, minimizing background noise, and eliminating reverberation seem prudent. For the retired population, emphasis should be placed on minimizing disability by promoting greater use of assistive devices and environmental redesign. Future laboratory studies of perceptual and psychomotor functions should attempt to sample more representatively and target underrepresented groups of older adults. New field studies are needed to bridge the gap between survey self-reports and laboratory studies and to determine the cost and benefits of redesign. PMID- 8194576 TI - Barriers to the design of vehicles for mature adults. AB - There are three barriers that must be overcome in designing vehicles to meet the needs of mature adults. These barriers are (a) the ages of the designers of the product, (b) young designers (and most of society's) perceptions of the capabilities of older adults, and (c) the lack of applied research on the interaction of older adults with their vehicles. This article addresses each of the three barriers and the challenges it brings to the vehicle design process. Emphasis is placed on the third barrier--the serious lack of applied research in the topic to support product designers in their work--because it is the most difficult to surmount. PMID- 8194577 TI - Implications of issues in typographical design for readability and reading satisfaction in an aging population. AB - The issues in typographical design that influence readability in an aging population are explored. The traditional response to age-related changes in vision has been "bigger is better," but we explore other major variables and vocabulary associated with page layout and design, including type classification and readability, justification, traditional rules of page composition, and issues of word forms versus character strategies. Other research areas that should be explored are also considered. PMID- 8194578 TI - Genetic ecology: a new interdisciplinary science, fundamental for evolution, biodiversity and biosafety evaluations. AB - Genetic ecology is the extension of our modern knowledge in molecular genetics to studies of viability, gene expression and gene movements in natural environments like soils, aquifers and digestive tracts. In such milieux, the horizontal transfer of plasmid-borne genes between phylogenetically distant species has already been found to be much more frequent than had been expected from laboratory experience. For the study of exchanges involving chromosomally-located genes, more has to be learned about the behaviour of transposons in such environments. The results expected from studies in genetic ecology are relevant for considerations of evolution, biodiversity and biosafety. The role of this new field of research in restoring popular confidence in science and in its biotechnological applications is stressed. PMID- 8194579 TI - Regulation of the retinal interphotoreceptor matrix Na by the retinal pigment epithelium during the light response. AB - We examined the rabbit retinal pigment epithelium (RPE) for Na transport properties which would allow it to buffer undesirable changes in Na concentrations in the interphotoreceptor matrix (IPM) during light and dark cycles. The RPE is selectivity permeable to sodium. Open and short circuit transport studies with RPE indicate a circulating (choroid to retina and back) Na current which does not compromise the electrical integrity of the blood brain barrier but together with the Na permselectivity is of sufficient magnitude to buffer both upwards and downwards movements of IPM [Na] during light or dark responses. PMID- 8194580 TI - Testicular compensatory hypertrophy in the unilaterally adrenalectomized lizard Mabuya carinata (Schn.). AB - Unilateral adrenalectomy in recrudescent and breeding phases of the reproductive cycle caused atrophic changes in the ipsilateral testis, shown by inhibition of spermatogenic and steroidogenic activity of the ipsilateral testis. The contralateral testis showed compensatory hypertrophy. Unilateral adrenalectomy in regressing and quiescent phases of the reproductive cycle did not induce compensatory hypertrophy in the contralateral testis although there were atrophic changes in the ipsilateral testis. PMID- 8194581 TI - RH-5849, a nonsteroidal ecdysone agonist, does not mimic makisterone-A in Dysdercus koenigii. AB - The response of final instar nymphs of Dysdercus koenigii to topical application of the non-steroidal ecdysone agonist, RH-5849, was dose dependent. The candidate compound produced mortality even at moderate doses, but precocious adult development was not observed. Similar results were obtained after oral administration or injection. Conversely, injections of makisterone-A (the principal moulting hormone of Dysdercus) into 5th instar nymphs resulted in precocious adult development within 4 days. We conclude that RH-5849 does not mimic makisterone-A, as is the case with ecdysone, and that toxicity is mediated instead through non-endocrine targets in this insect species. PMID- 8194582 TI - Effects of chronic caffeine feeding on the activities of oxygen free radical defense enzymes in the growing rat heart and liver. AB - The purpose of the present study was to determine the relationship between concentration of Zn, Cu and Fe, and the catalase, glutathione peroxidase and superoxide dismutase activities in the heart and liver of newborn rats whose dams were fed a diet supplemented with caffeine. Heart Zn levels of the 22- and 30-day old rats of the caffeine group showed a decrease, whereas liver Zn levels showed an increase compared to the control. Cu levels in the liver at day 22 in the caffeine group were less than in the control. Cu- and Zn-containing superoxide dismutase activities showed an increase in the hearts of the caffeine group compared to the control. The activity of catalase and glutathione peroxidase showed no difference in the heart and liver between the groups. The present study suggests the possible involvement of superoxide dismutase enzyme in the impairment of heart formation as a result of chronic caffeine intake in the early growing period. PMID- 8194583 TI - Alleviation of mortality induced by salicylate and stress. AB - Protection from the deleterious effects of the interaction of environmental stress and salicylate by calcium supplement was investigated in 96 pigmented rats. Within a 2 x 2 x 4 factorial design, rats were assigned to groups defined by: A) ad lib access to 1) plain tap water, or 2) 50 mM calcium chloride solution; B) exposure to stressors consisting of daily 10 h periods of 1) 98 dB SPL noise, or 2) confinement precluding movements; C) daily injections of 233, 350, or 410 mg/kg of sodium salicylate or the saline vehicle. For subjects maintained on tap water, weight loss and mortality increased with salicylate levels, with all subjects dying in the group drinking water and injected with 410 mg/kg. Calcium protected all of the subjects in the noise stress group but not in the confined group. PMID- 8194584 TI - Baclofen prevents rapid amygdala kindling in adult rats. AB - This study investigates the effect of the gamma-aminobutyric acid (GABAB) agonist, baclofen, on amygdala kindling in adult rats. Baclofen has been reported to be anticonvulsant in a variety of seizure models and prevents kindling in immature rats. These experiments describe the effects of baclofen (2, 5 and 10 mg/kg, i.p.) on the afterdischarge threshold and kindling rate. Baclofen, 10 mg/kg, significantly increased the afterdischarge threshold in the amygdala. Baclofen at 5 and 10 mg/kg, retarded the rate of kindling as measured by the number of stimuli required to advance to subsequent seizure stages. These results suggest that baclofen may decrease the local excitability of the amygdala and retard the rate of seizure spread (or generalization) throughout the brain. Baclofen, acting at GABAB receptors exerts an anticonvulsant effect on amygdala kindling in these experiments. PMID- 8194585 TI - Divergent effects of hyperosmolality on stress-response (heat shock) protein expression in cultured human tumor cells: an immunocytochemical study. AB - Exposing cells to adverse conditions usually elicits expression of stress response (heat shock) proteins (srp). Here we show that hyperosmolar growth conditions do not uniformly affect srp expression in MCF-7 and HeLa S3 cells, derived from carcinoma of the breast and cervix, respectively. Thus, whereas srp 27 expression was increased in MCF-7, but not in HeLa S3, the opposite was the case with srp 72. On the other hand, hyperosmolality did not induce alpha B crystallin or ubiquitin in either cell line. These findings show that srp expression by the human tumor cells studied is non-coordinate, suggesting that each srp is independently modulated. PMID- 8194586 TI - Priming effect of vasoactive intestinal peptide on the respiratory burst of neutrophils non-mediated by plasma membrane receptors. AB - Vasoactive intestinal peptide (VIP) primed the respiratory burst of human neutrophils in response to phorbol myristate acetate. Maximal and half-maximal effects were achieved at 10 and 0.5 nM VIP respectively. The absence of plasma membrane receptors to VIP in neutrophils suggests that priming of the respiratory burst should be considered as a side effect of VIP. However, from the above indicated concentration range, the priming of the neutrophil by VIP cannot be considered as a pharmacological effect. The enhancement of the formation of reactive oxygen metabolites by VIP may be important in the pathology of VIP producing tissues. PMID- 8194587 TI - Antiproliferative effect of polyunsaturated fatty acids and interleukin-2 on normal and abnormal human lymphocytes. AB - The polyunsaturated fatty acids (PUFAs), linoleic acid (LA), alpha linolenic acid (ALA), gamma linolenic acid (GLA), arachidonic acid (AA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), showed inhibition of growth of both normal and abnormal (Molt-4) human lymphocytes, and inhibition was concentration dependent. Interestingly, the production of the lymphokine Interleukin-2 (IL-2) was elevated in Molt-4 cells, but it was reduced in the normal human lymphocytes. Addition of GLA or IL-2 or a combination of both showed enhancement of SO2.- and of lipid peroxidation levels, which were significantly higher in Molt-4 cells than in the normal lymphocytes. Reduction of protein concentration was also observed in both types of cells during this treatment. The data showed that the antiproliferative effects of GLA and IL-2 may partly be exerted through the elevated production of superoxide free radicals and peroxidation products. This is a novel finding and therefore, further exploitation of combinations of PUFAs and IL-2 may be a possible way of combating cancer cell growth. PMID- 8194588 TI - Increased incidence of unpartnered single chromatids in metaphase II oocytes in 39,X(XO) mice. AB - Since rare cases of sex chromosome anomalies such as XXX and XXY were observed in the offspring of our XO breeder mice, we performed a cytogenetic analysis of metaphase II oocytes of XO mice to determine whether any changes in chromosomal configurations occur. We found a significantly increased incidence of unpartnered single chromatids in metaphase II oocytes of XO mice. Such single chromatids may contribute to embryonic aneuploidy. In addition, the tendency of the X-chromosome to segregate non-randomly to the oocyte rather than to the polar body was confirmed. PMID- 8194589 TI - Inhibition and sex specific induction of spawning by serotonergic ligands in the zebra mussel Dreissena polymorpha (Pallas). AB - Serotonin (5-hydroxytryptamine, 5-HT) stimulates spawning in the zebra mussel (Dreissena polymorpha), a macrofouling European bivalve that has recently invaded North America. To develop methods of controlling zebra mussel spawning, two vertebrate serotonin antagonists, methiothepin and metergoline, known to bind with high affinity to snail 5-HT receptors, were tested for their ability to block 5-HT-induced spawning in zebra mussels. Methiothepin inhibited 5-HT-induced spawning at concentrations as low as 10(-6) M. Metergoline (10(-4) M) inhibited 5 HT-induced spawning; however, at lower concentrations (10(-8) to 10(-5) M), metergoline by itself significantly induced spawning in male, but not female zebra mussels. Metergoline (10(-5) M)-induced male spawning was inhibited by 10( 5) M methiothepin. Thus, methiothepin is the most effective inhibitor and metergoline the most powerful inducer of spawning yet tested in zebra mussels. PMID- 8194590 TI - Activation of Na,K-ATPase by an endogenous peptide, PEC-60. AB - Several peptidic and non-peptidic factors can modulate Na,K-ATPase activity, among them mainly inhibitors of this enzyme, ouabain being the most effective. In a very few cases only, activation of Na,K-ATPase by endogenous factors has been recorded. We have investigated the effect on Na,K-ATPase of a novel regulatory peptide, PEC-60, recently isolated from porcine intestine. Various biological effects have been described for PEC-60 in different tissues, including brain. We have found that PEC-60 caused a dose-dependent activation of Na,K-ATPase from rat brain frontal cortex, whereas the carboxymethylated form of PEC-60 or other hormonal peptides had no effect. The maximal value of activity reaches up to 125% at close to micromolar concentrations of PEC-60 and the dependence can be described with a bell-shaped curve, indicating a complex mechanism for the interaction. The activation of the enzyme by PEC-60 is apparently related to Na(+)-dependent steps of the Na,K-ATPase system. The kinetic parameters for K(+) phosphatase were unaffected. Moreover, the activating effect was enhanced by preincubation at low concentrations of ATP that transform the enzyme into the Na(+)-form. Due to the crucial physiological role of Na,K-ATPase, its activity has to be finely controlled and thus PEC-60 may be one of the endogenous factors that regulate this enzyme. PMID- 8194591 TI - Human progelatinase A can be activated by matrilysin. AB - The activation of human progelatinase A by other matrix metalloproteinases was studied by following both the loss of its N-terminal propeptide and the accompanying increase in the rate of hydrolysis of a synthetic substrate. Activated stromelysin 1 was unable to cause any activation of progelatinase A beyond that slowly occurring by autolysis, but an 8 h incubation with activated matrilysin was able to produce 64% of the activity generated by incubation with (4-aminophenylmercuric)acetate (APMA). Wild-type progelatinase A and a mutant proenzyme that cannot become active were both cleaved by matrilysin to a lower molecular weight species that had lost the propeptide. This shows that matrilysin activates progelatinase A by removing the propeptide in a process that does not require any autolytic cleavages. PMID- 8194592 TI - CT-boxes are involved in control of the rat insulin II gene expression. AB - Expression of the rat insulin II gene is controlled mainly at the level of transcription initiation by multiple factors binding to specific cis-acting DNA elements in the regulatory region. We have shown that two elements (CT-motifs) located between nucleotides -83 and -76 (CT-1) and -204 and -197 (CT-2) are involved in transcriptional regulation in the insulin-producing cell line HIT M2.2.2. Transient expression analysis of 5'-deletion as well as block replacement mutants revealed that CT-1 and CT-2 are mutational sensitive. Gel mobility shift assays showed that both motifs bind similar nuclear factors. Our results suggest the involvement of a third CT-motif located directly upstream of CT-2 on the complementary strand. PMID- 8194593 TI - Prediction of the structural similarity between spermidine/putrescine-binding protein and maltose-binding protein. AB - A structural similarity between spermidine/putrescine-binding protein and maltose binding protein has been predicted by a sequence-structure compatibility method. The sequence alignment obtained by this method revealed a consensus sequence motif located on the surface loop between the first alpha-helix and the second beta-strand, and the further analysis identified a similar motif in iron-binding protein. The conservation of this motif among certain bacterial periplasmic binding proteins suggests a common functional role for this region as well as an evolutionary relationship between them. PMID- 8194594 TI - Identification of two distinct synucleins from human brain. AB - Two abundant proteins of 140 and 134 amino acids were purified and sequenced from human brain. They were identified through their reactivity on immunoblots with a partially characterised monoclonal antibody that recognises tau protein in a phosphorylation-dependent manner. The 140 amino acid protein is identical with the precursor of the non-A beta component of Alzheimer's disease amyloid which in turn is highly homologous to synuclein from Torpedo electroplaques and rat brain. The 134 amino acid protein is the human homologue of bovine phosphoneuroprotein 14; it is 61% identical in sequence to the 140 amino acid protein. The previously unrecognised homology between these two proteins defines a family of human brain synucleins. We refer to the 140 and 134 amino acid proteins as alpha-synuclein and beta-synuclein, respectively. Both synucleins are expressed predominantly in brain, where they are concentrated in presynaptic nerve terminals. PMID- 8194595 TI - Alzheimer's beta-amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme. AB - Cerebral deposition of beta-amyloid peptide (beta A) is a hallmark of Alzheimer's disease. Concentration of beta A could play a critical role in the rate of amyloid deposition. It is therefore of considerable importance to identify proteases involved in processing of beta A. 125I-labeled synthetic beta A specifically cross-linked to a single protein with M(r) = 110,000 in cytosol fractions from rat brain and liver. This protein was identified as insulin degrading enzyme (IDE) since the labeling of the 110 kDa protein was completely blocked by an excess of insulin, and anti-IDE monoclonal antibodies precipitated the labeled protein. Purified rat IDE effectively degraded beta A. PMID- 8194596 TI - The interaction of metal ions with annexin V: a crystallographic study. AB - Three closely related rhombohedral crystal structures of human annexin V have been analysed and compared: a low-calcium, a high-calcium and an ytterbium-soaked crystal. The occupancy of the calcium sites increases at higher calcium concentrations, but the calcium is removed rather than replaced during soaking in the ytterbium solution. Instead, other sites are substituted at high calcium concentrations as well as in the presence of ytterbium. Furthermore, a new site is revealed in the ytterbium-soaked crystal which may give a clue to the mechanism of conformational change that takes place in the third domain of annexin V in the presence of very high calcium concentrations and of phospholipids. PMID- 8194597 TI - Protein kinase C inhibitors induce apoptosis in human malignant glioma cell lines. AB - Previous work has demonstrated the importance of the protein kinase C (PKC) system in regulating glioma growth, and has led to clinical trials utilizing PKC inhibitors as adjuncts in the therapy of patients harboring malignant gliomas. This study was performed to explore the possibility that inhibition of PKC in gliomas was triggering an apoptosis signal. Glioma cell lines were treated with PKC inhibitors staurosporine (10 nM), and tamoxifen (10 microM). DNA from cells treated with each of these drugs exhibited a 'ladder' pattern of oligonucleosome sized fragments characteristic of apoptosis, thus suggesting that in glioma cells, these drugs may be cytocidal in action. PMID- 8194598 TI - Nonendothelial-derived nitric oxide activates the ATP-sensitive K+ channel of vascular smooth muscle cells. AB - To determine whether endogenous nitric oxide (NO) opens the ATP-sensitive K+ channel (KATP channel), we investigated the effect of nonendothelial-derived NO on this channel in cultured smooth muscle cells of the porcine coronary artery by the patch-clamp technique. In the cells pretreated with endotoxin, the addition of 10(-4) M L-arginine generated NO and activated the KATP channel. Activation of this channel was suppressed by pretreatment with 10(-3) M NG-methyl-L-arginine or 10(-3) M Nx-nitro-L-arginine methyl ester, each of which is a specific antagonist of the L-arginine-NO pathway, and by 10(-6) M Methylene blue, which blocks guanylate cyclase. The activation of the KATP channel by L-arginine-NO pathway is expected to produce hyperpolarization of the cell membrane and relaxation of vascular smooth muscle cells. PMID- 8194599 TI - Structural similarity of cytochrome c2 from Rhodopseudomonas viridis to mitochondrial cytochromes c revealed by its crystal structure at 2.7 A resolution. AB - The crystal structure of cytochrome c2 from Rhodopseudomonas viridis has been refined using molecular dynamics and restrained least-squares methods to a crystallographic R-factor of 0.216 at 2.7 A resolution. A structural comparison between Rps. viridis cytochrome c2 and the other bacterial cytochromes c2 or mitochondrial cytochromes c indicates that the overall protein foldings are very similar to each other with the exception of the surface loop and terminal region of the polypeptide chain. However, the position and hydrogen-bond pattern of the evolutionarily conserved water molecule buried within the heme binding pocket in Rps. viridis cytochrome c2 are common to those in the mitochondrial cytochromes c. This fact indicates that Rps. viridis cytochrome c2 is structurally more similar to mitochondrial cytochromes c than to the other bacterial cytochromes c2. PMID- 8194601 TI - X-band ESEEM spectroscopy of 15N substituted native and inhibitor-bound superoxide dismutase. Hyperfine couplings with remote nitrogen of histidine ligands. AB - The hyperfine couplings of the remote nitrogens of histidine ligands are determined for the first time by an X-band ESEEM spectroscopy study of 15N substituted superoxide dismutase (SOD). They show a significant difference between two groups of ligands with different orientation relative to the metal ion. The ESEEM spectra of 15N SOD with cyanide as an inhibitor containing 14N and 15N are also discussed. They allow some conclusions to be drawn about structural changes upon inhibitor binding and indicate the necessity of further multifrequency investigations. PMID- 8194600 TI - Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases. AB - Incubation of rat skeletal muscle mitochondria with the nitric oxide generator, S nitrosoglutathione (GSNO) reversibly inhibited oxygen utilisation with all substrates tested. The visible absorption spectra of the inhibited mitochondria showed that cytochromes c+c1, b and a+a3 were reduced, indicating a block at the distal end of the respiratory chain. Analysis of the respiratory chain enzyme activities in the presence of GSNO localised the site of inhibition of cytochrome c oxidase alone. These results indicate that nitric oxide is capable of rapidly and reversibly inhibiting the mitochondrial respiratory chain and may be implicated in the cytotoxic effects of nitric oxide in the CNS and other tissues. PMID- 8194602 TI - Vacuolar ATPase inactivation blocks recycling to the trans-Golgi network from the plasma membrane. AB - TGN38/41 is an integral membrane protein which recycles between the trans-Golgi network (TGN) and the cell surface but is predominantly located in the TGN of rat (NRK) cells at steady state. As part of our studies on the mechanism and route of recycling between the TGN and the cell surface we have used chloroquine or Bafilomycin A1 to modulate the lumenal pH of endocytic organelles. The data we present demonstrate that inactivation of the proton pump which maintains the acidic environment within the lumen of endocytic organelles leads to an accumulation of TGN38/41 in early endosomes. These data confirm the observation that TGN38/41 recycles between the plasma membrane and the TGN and identifies a specific block in that recycling pathway. PMID- 8194604 TI - Prothymosin alpha binds to histone H1 in vitro. AB - Previous studies have shown that prothymosin alpha (ProT alpha) is a nuclear acidic protein implicated in cell proliferation. To identify proteins that interact with ProT alpha we have used ligand-blotting assays. We report here that purified ProT alpha binds specifically to histone H1 in a dose dependent manner. Polyglutamic acid, an analog of the central acidic domain of ProT alpha, strongly inhibits the above interaction, suggesting that the binding of ProT alpha to histone H1 is mediated through its acidic domain. PMID- 8194603 TI - Thyroid hormones increase insulin-like growth factor mRNA levels in the clonal osteoblastic cell line MC3T3-E1. AB - Thyroid hormones are known to affect skeletal growth and maturation by influencing both bone resorption and bone formation. Their exact mechanism of action, however, is still unknown. Local factors such as prostaglandins, TGF-beta or IGF-I were suggested to mediate their effects. Thyroid hormones were reported to stimulate expression of IGF-I mRNA in liver and kidney and to increase IGF-I release from bone organ cultures and osteoblast-like cells. Therefore we studied the effect of thyroid hormones on IGF-I mRNA expression in MC3T3-E1 cells. The cells were grown in culture for 5 to 7 days and treated with triiodothyronine (10(-11)-10(-6) M) and thyroxin (10(-6) M) for 1-24 h. Cellular mRNA was isolated and subjected to Northern hybridization. The amount of IGF-I mRNA, which is already expressed in this cell line under control conditions, was markedly enhanced by T3 and T4. This effect was found to be dose-dependent with a maximum at 10(-7) M and could already be seen after 3 h increasing up to 24 h. Our findings indicate that IGF-I expression in osteoblasts is directly regulated by thyroid hormones. We conclude that IGF-I expression belongs to the phenotypic characteristics of mature osteoblasts, and that thyroid hormones play an important role in differentiation of MC3T3-E1 cells along the osteoblastic lineage. PMID- 8194605 TI - Characterization of the paramagnetic iron-containing redox centres of Thiosphaera pantotropha periplasmic nitrate reductase. AB - Electron paramagnetic resonance spectroscopy signals attributable to low-spin haem c in the oxidised protein and [4Fe-4S]1+ in the dithionite-reduced protein were identified, at low temperature, in Thiosphaera pantotropha periplasmic nitrate reductase. Spin integration of these signals as well as elemental analysis suggest a stoichiometry of 1.3-1.6 c-haem and 1 [4Fe-4S] cluster per enzyme molecule. The Em (at pH 7.4) of the [4Fe-4S]2+,1+ couple, -160 mV, means that it is unlikely to be physiologically reducible. Peptide sequences from the 90 kDa subunit indicate that the enzyme is a member of the family of molybdopterin guanine dinucleotide-binding polypeptides, the majority of which possess a putative [4Fe-4S] cluster binding sequence and thus may also bind a (low potential) iron-sulphur cluster. PMID- 8194606 TI - Identification of the U-937 membrane-associated proteinase interacting with the V3 loop of HIV-1 gp120 as cathepsin G. AB - We have purified a serine proteinase from the membrane of U-937 cells that was inhibited in a tight-binding manner by recombinant gp120 and by peptides mimicking the V3 loop of gp120 [(1993) FEBS Lett. 317, 167-172]. This proteinase has now been characterized, both structurally and functionally. It has a dual trypsin- and chymotrypsin-like specificity, and N-terminal sequence analysis of the first 32 residues indicates complete identity with leukocyte cathepsin G. Cathepsin G-like material was located at the surface of U-937 cells using a monoclonal antibody directed against leukocyte cathepsin G, and polyclonal anti cathepsin G antibodies precipitated the purified proteinase. However, the U-937 enzyme differs slightly from commercial leukocyte cathepsin G in its apparent M(r) because of different glycosylation. No other protein structurally related to cathepsin G was found upon screening a U-937 cDNA library using several oligonucleotide probes constructed from the membrane proteinase N-terminal amino acid sequence. The possible interaction of a cathepsin G-like proteinase at the surface of U-937 cells with the V3 loop of HIV-1 gp120 is discussed. PMID- 8194607 TI - The Pseudomonas phytotoxin coronatine mimics octadecanoid signalling molecules of higher plants. AB - The phytotoxic principle, coronatine, which is present in several pathovars of the plant pathogen, Pseudomonas syringae was shown to be highly active in completely different, jasmonate-selective bioassays. At nanomolar to micromolar concentrations, coronatine induced the accumulation of defense-related secondary metabolites in several plant cell cultures, induced transcript accumulation of the elicitor-responsive gene encoding the berberine bridge enzyme of Eschscholtzia californica, as well as the coiling response of Bryonia dioica tendrils. Biological activity critically depended upon the structure of coronatine, and slight modifications, such as methylation of the carboxyl moiety or reduction of the carbonyl group, rendered the molecules almost inactive. Coronafacic acid, obtained by hydrolysis of coronatine, was also nearly inactive. Coronatine did not elicit the accumulation of endogenous jasmonic acid in the systems analyzed. While coronafacic acid is similar in structure to jasmonic acid, we found coronatine to be a close structural analogue of the cyclic C18 precursor of jasmonic acid, 12-oxo-phytodienoic acid. The phytotoxic symptoms produced by coronatine can now be understood on the basis of the toxin's action as a mimic of the octadecanoid signalling molecules of higher plants. PMID- 8194608 TI - Antisperm antibodies: origin, regulation, and sperm reactivity in human infertility. AB - OBJECTIVE: To follow-up and expand discussion on the action mechanisms of antisperm antibodies in human infertility, the etiology and control of antisperm antibody induction, sperm antigens involved in immunoinfertility, and strategies for therapy. DESIGN: A review of the recent literature with an emphasis on female immunoinfertility. RESULTS: The role of antisperm antibodies in clinical infertility continues to be defined. Through assisted reproductive technologies, antisperm antibodies were shown to exert detrimental effects on different prefertilization and possibly postfertilization events. The female reproductive tract is part of the common mucosal immune system and is able to mount effective immune responses against infectious agents, foreign antigens, and, occasionally, sperm cells. Sperm membranes and constituents contain numerous antigenic components foreign to the human body, and yet antisperm antibodies become problematic in few women exposed to semen. Semen and sperm cells contain immunosuppressive factors capable of inhibiting different immune cells. Fertile women apparently produce antisperm antibodies but also possess neutralizing serum anti-idiotypic antibodies that are lacking in virgin and immunoinfertile women. CONCLUSIONS: Antisperm antibodies can affect adversely human fertility but normally may be controlled by anti-idiotypic antibodies, which along with immunosuppressor factors in semen prevent their induction to a significant degree. This balance between detrimental and "beneficial" immune response to sperm may be shifted toward an antisperm antibody response by stimulatory factors such as infection. Therapies may be devised to stimulate the anti-idiotypic antibody system, to induce immune tolerance to sperm antigens, and to use antigens to adsorb antisperm antibodies from spermatozoa. PMID- 8194609 TI - The somatotrophic axis and the reproductive process in health and disease. PMID- 8194610 TI - The discriminatory human chorionic gonadotropin zone for endovaginal sonography: a prospective, randomized study. AB - OBJECTIVE: To determine the probability of detecting the gestational sac of a normal intrauterine pregnancy by vaginal ultrasound at different gestational ages and serum hCG concentrations. DESIGN: Prospective, randomized study. SETTING: Pregnant human volunteers in a university-based clinical research environment. PATIENTS: Women with viable pregnancies who conceived spontaneously or after ovulation induction. INTERVENTIONS: Vaginal ultrasound and serum hCG determinations were performed between 20 and 30 days after conception. The timing of the tests was determined randomly. MAIN OUTCOME MEASURE: Detection of gestational sac. RESULTS: The probability of detecting a gestational sac increased significantly with both gestational age and serum hCG concentration, but the regression on gestational age fitted the data much better than the regression on loge (hCG). The probability of detecting a sac was similar in multiple and singleton pregnancies of the same gestational age but, for a given hCG concentration, the probability of detecting a sac was lower for multiple than for singleton pregnancies because multiple gestations were associated with higher serum hCG concentrations than singleton pregnancies of the same gestational age. CONCLUSION: If it is known, gestational age rather than the serum hCG concentration should be used to determine whether the gestational sac of an intrauterine pregnancy should be detectable by vaginal ultrasound. Failure to image a gestational sac > or = 24 days after conception is presumptive evidence of an ectopic pregnancy. Reliance on serum hCG rather than gestational age may lead to an erroneous diagnosis of ectopic pregnancy in women with multiple pregnancies. PMID- 8194611 TI - Absence of a dose-response effect of leuprolide acetate on leiomyomata uteri size. AB - OBJECTIVE: To evaluate the effects of two different doses (3.75 mg versus 7.5 mg) of leuprolide acetate (LA, Lupron; Tap Pharmaceuticals, Deerfield, IL) on myoma size, blood loss during myomectomy, on magnetic resonance imaging (MRI) signal quality, and histopathologic changes in women requiring myomectomy. DESIGN: Prospective, nonrandomized, sequential study. SETTING: Urban center teaching hospital. PATIENTS: Twenty-eight women with uterine leiomyomata requiring myomectomy. INTERVENTIONS: Nine women were entered as controls (group 1), 10 women received 3.75 mg IM (group 2), and 9 women received 7.5 mg IM of LA (group 3) each for 3 months before myomectomy. RESULTS: The uterine size and hematocrit among the three groups of patients before treatment was not significantly different. A significant reduction of 34.5% and 34.6% in myomata size was seen in groups 2 and 3. The estimated average blood loss at myomectomy was 745 +/- 101 mL, 615 +/- 177 mL, and 722 +/- 192 mL in groups 1, 2, and 3, respectively. The postoperative hematocrit was not different among the three groups (29.8% +/- 0.9%, 30.4% +/- 1.6%, and 29.8% +/- 1.2%). There was no evidence of cytologic atypia, increased mitosis, or change in fibrosis in LA-treated women. There were no characteristic MRI or histologic changes seen after LA treatment as compared with controls. CONCLUSIONS: The results of this study have demonstrated that both doses of LA (3.75 and 7.5 mg) can induce a significant and similar degree of size reduction in myomas and that neither dose of LA aided in the reduction of blood loss at myomectomy and therefore should not be used routinely. PMID- 8194612 TI - Benefits of continuous physiological pulsatile gonadotropin-releasing hormone therapy in women with polycystic ovarian syndrome. AB - OBJECTIVE: Can continuous pulsatile GnRH from one ovulatory cycle to another enhance the endocrine milieu of women with polycystic ovarian syndrome (PCOS)? DESIGN: Five women with well-characterized, clomiphene citrate (CC)- and hMG resistant PCOS were treated with a 100 ng/kg per bolus of IV pulsatile GnRH (Lutrepulse; Ortho Pharmaceutical Corporation, Raritan, NJ) every 90 minutes for two consecutive ovulatory cycles. Weekly vaginal ultrasonography and daily blood sampling for LH (mIU/mL), FSH (mIU/mL), E2 (pg/mL), and P (ng/mL) were performed. These data were compared with a control group of normally cycling women. RESULTS: First ovulatory cycles on therapy were characterized by significantly increased mean follicular phase LH = 88 (arbitrary units area under the curve [AUC]) compared with second cycles (28 mean AUC units) and controls (13 mean AUC units). Luteal phase E2 (3,081 mean AUC units) was significantly increased in first cycles compared with second cycles (880 mean AUC units) and controls (1,562 mean AUC units in PCOS). Luteal phase E2 secretion was elevated in second cycles when compared with normal but not significantly. The changes occurring between the first and second ovulatory cycles in women with PCOS resulted in a more physiological overall pattern of gonadotropin and sex steroid secretion in the second cycles. Two singleton pregnancies were achieved in the second cycle. CONCLUSIONS: Low-dose pulsatile IV GnRH can successfully induce ovulation in women with PCOS who have failed to conceive on all previous conventional therapy (CC, hMG, and/or GnRH agonist, and hMG). Continuous cycle-to-cycle physiological GnRH replacement normalized the endocrine parameters of second cycles. Women with PCOS, even when ovulatory on pulsatile GnRH, do not display entirely normal gonadotropin and sex steroid dynamics. PMID- 8194613 TI - The endoscopic localization of endometrial implants in the ovarian chocolate cyst. AB - OBJECTIVE: To describe the characteristics of the endometrial cyst and to locate the implants for selective biopsy. DESIGN: Prospective study. SUBJECTS: Fifty-one women with one or two ovarian chocolate cysts of 3 cm or more were investigated. INTERVENTIONS: Laparoscopy and random biopsy versus a new technique of ovarioscopy and selective biopsy. MAIN OUTCOME MEASURE: Visual characteristics and histopathology of endometrial cysts. RESULTS: The clinical suspicion of an endometrioma was confirmed in a series of 59 hemorrhagic cysts by histopathology in 89% and 42%, respectively, of typical and atypical cases and in 27% of recurrent chocolate cysts in the presence of postoperative adhesions. The atraumatic technique of ovarioscopy allowed description of the typical characteristics of the inner wall of the endometrioma and location of the active implants for biopsy. Endometrial tissue was obtained by small ovarioscopy-guided biopsies in 82% of the cases versus 42% in large random biopsies. Red lesions were highly significant for a mucosa-type implant and were predominantly located at the site of invagination stigma and adhesions with the pelvic wall. CONCLUSIONS: Endoscopy of ovarian chocolate cysts allows observation of typical features of the wall that differentiates it from other benign cysts of the ovary. Microbiopsies obtained under endo-ovarian endoscopy provided significantly more active, endometrial tissue than random biopsies. The data confirm that in most cases the endometrioma is formed by invagination of the cortex and that active implants are located at the site of invagination. Ovarioscopy is therefore proposed as a useful tool to differentiate in doubtful cases between a hemorrhagic functional and an endometriotic cyst and to select the sites for biopsies. PMID- 8194614 TI - Effect of naloxone on luteinizing hormone secretion in premenstrual syndrome. AB - OBJECTIVES: To investigate the theory of brain opioid activity disregulation in premenstrual syndrome (PMS) and to discover the changes of central beta-endorphin activity during the menstrual cycle in PMS patients. DESIGN: Prospective study. SETTING: University-based PMS clinic. PATIENTS: All the patients and controls were between 20 and 45 years of age, with regular menses for at least six previous cycles. All the patients demonstrated at least 30% score increase in designated symptoms on the Visual Linear Analog Scale during the luteal phase compared with the follicular phase. In contrast, the score changes in the controls were < 30%. INTERVENTIONS: All subjects underwent LH-releasing hormone (LH-RH) stimulation test on days 2 to 3 of the cycle. Five naloxone infusions were administered on days 7 to 8 and 10 to 11, 1 day, 3 to 4 days, and 12 to 13 days after the LH surge as detected by the ovulation prediction kit. MAIN OUTCOME MEASURES: Luteinizing Hormone levels were recorded for 1 hour, followed by naloxone infusion at 2 mg/h for 4 hours. Blood samples were collected for LH tests every 15 minutes for 1 hour before, during, and for 1 hour after the infusion. RESULTS: All subjects had similar LH response to LH-RH. The integrated area of LH response to naloxone as expressed by percentage of the baseline on each of the 5 days did not show significant differences between the patients and the controls. CONCLUSIONS: The central beta-endorphin changes, if any, in PMS patients could not be demonstrated in our study. PMID- 8194615 TI - Microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection: a new effective approach to infertility as a result of congenital bilateral absence of the vas deferens. AB - OBJECTIVE: To present and assess the efficacy of a new approach for the treatment of infertility due to congenital bilateral absence of the vas deferens. DESIGN: A retrospective study of consecutive trials. SETTING: Centre for Reproductive Medicine, which is a tertiary referral institution. PATIENTS: Twelve couples suffering from infertility because of congenital bilateral absence of the vas deferens. INTERVENTIONS: A microsurgical epididymal sperm aspiration procedure was performed in the husbands, followed by intracytoplasmic sperm injection of oocytes recovered from the wives. Cleaving embryos were transferred to the uterine cavity 48 hours after the intracytoplasmic sperm injection procedure. MAIN OUTCOME MEASURES: Sperm parameters after microsurgical epididymal sperm aspiration, fertilization, cleavage, and pregnancy rates. RESULTS: In all 14 microsurgical epididymal sperm aspiration procedures, sperm was retrieved. Notwithstanding the poor quality of this epididymal sperm, a fertilization rate of 58% was achieved after intracytoplasmic sperm injection. On 10 occasions, embryos were transferred and five patients became pregnant, i.e., an overall pregnancy rate of 35.7% per started trial and 50.0% per transfer. Another two patients became pregnant after replacement of frozen-thawed embryos, which increases the pregnancy rate to 50.0% per microsurgical epididymal sperm aspiration procedure. Early pregnancy wastage was 57%, limiting the ongoing pregnancy rate to 21.4% per microsurgical epididymal sperm aspiration procedure. CONCLUSION: This study shows the combined microsurgical epididymal sperm aspiration-intracytoplasmic sperm injection procedure to be highly efficient in achieving fertilization in vitro, even after recovery of grossly impaired epididymal sperm. PMID- 8194616 TI - Comparison of natural with clomiphene citrate-stimulated cycles in in vitro fertilization: a prospective, randomized trial. AB - OBJECTIVE: To compare the outcome of natural with clomiphene citrate (CC) stimulated cycles in IVF. DESIGN: Prospective, randomized study. SETTING: Tertiary referral center for assisted conception. SUBJECTS: Thirty patients randomized to receive either no treatment (n = 14) or CC, 100 mg, from days 2 to 6 (n = 16). INTERVENTIONS: Daily ultrasound (US) scan and measurements of serum LH and E2. Ovarian morphology was assessed on baseline US scan. Human chorionic gonadotrophin was administered when the mean diameter of the dominant follicle reached 17 mm. Transvaginal US-directed oocyte recovery was performed 35 hours later. MAIN OUTCOME MEASURES: The number of patients reaching oocyte recovery; numbers of oocytes collected, fertilized and embryos transferred; and clinical pregnancy and multiple pregnancy rates (PRs) were recorded. RESULTS: Ten cycles in the natural cycle group were abandoned before oocyte recovery compared with none in the CC group. There were significantly more follicles > 14 mm (2.4 +/- 0.3 [SE] compared with 0.9 +/- 0.2) and higher peak levels of E2 (375 +/- 67 pg/mL (1,378 +/- 247 pmol/L) compared with 204 +/- 17 pg/mL (748 +/- 61 pmol/L)) in those receiving CC compared with those receiving no drug. All 16 patients treated with CC had oocyte retrieval (mean, 1.8 +/- 0.3 oocytes) compared with only 4 in the natural cycle group (1 oocyte each). The oocyte recovery rate was 95%. Two patients conceived in the CC group (PR per ET, 18%) compared with none in the natural cycle group. Patients with polycystic ovaries developed more large follicles than those with normal ovaries. No patient developed ovarian hyperstimulation syndrome. CONCLUSIONS: Patients undergoing natural cycle IVF are more likely to have abandoned cycles, produce fewer follicles and oocytes, and are less likely to reach ET than patients treated with CC alone. Clomiphene citrate should be considered for use in the context of a conventionally organised IVF-ET program if a mild degree of ovarian stimulation is desired. PMID- 8194617 TI - High dosages of gonadotropins are associated with poor pregnancy outcomes after in vitro fertilization-embryo transfer. AB - OBJECTIVE: To compare the pregnancy outcomes during IVF-ET when different dosages of hMG are used after follicular phase suppression with leuprolide acetate (LA). DESIGN: Retrospective chart review. SETTING: Hospital-based IVF-ET program. PATIENTS: From January 1990 to December 1992, 264 cycles reached ET after LA downregulation and gonadotropin stimulation. RESULTS: Higher doses of gonadotropins, as measured by both average daily dose and total dose per cycle, were associated with lower clinical pregnancy rates. This effect was independent of age, basal FSH level, endometrial thickness, maximal E2 levels, number of eggs retrieved, and embryos transferred. CONCLUSION: High dosages of exogenous gonadotropins are associated with lower pregnancy rates in IVF-ET. PMID- 8194618 TI - Transferring more embryos increases risk of heterotopic pregnancy. AB - OBJECTIVES: To analyze symptoms and signs that may distinguish heterotopic pregnancy from solely ectopic pregnancy (EP) after IVF. To determine if the number of embryos transferred is a risk factor for heterotopic compared with solely EP. DESIGN: Retrospective cohort of 587 IVF pregnancies, 328 with distorted tubal anatomy. SETTING: University Hospital, London, a referral center for Ontario provincial government-supported assisted reproductive technologies. PARTICIPANTS: Couples undergoing IVF. INTERVENTION: None. MAIN OUTCOME MEASURES: Heterotopic pregnancy, solely EP, intrauterine pregnancy, and distorted pelvic anatomy. RESULTS: Of 587 pregnancies, 7 were heterotopic pregnancies and 24 were solely EP, all in the subset of 328 women with distorted tubal anatomy. Symptoms, signs and time of diagnosis were not different between heterotopic and solely ectopic gestations. Compared with solely EP, heterotopic pregnancies were associated with transfer of more embryos. With four or more embryos transferred, the odds ratio for development of heterotopic versus solely ectopic gestation was 10.0. CONCLUSION: Heterotopic pregnancy occurred in 2% of gestations after IVF, all in women with distorted tubal anatomy. Transfer of four or more embryos was a risk factor for heterotopic pregnancy. PMID- 8194619 TI - The role of luteal phase support in infertility treatment: a meta-analysis of randomized trials. AB - OBJECTIVE: To determine whether the use of luteal phase support improves pregnancy rate (PR) in infertility. DESIGN: A meta-analysis of randomized trials of luteal phase support. Search of the National Library of Medicine MEDLINE data base from 1971 using the words luteal, pregnancy, human, and comparative. Bibliography of relevant articles, reviews, and abstracts of scientific meetings were hand searched. All randomized controlled trials of luteal phase support in infertility were included. Luteal phase support for recurrent abortion and nonrandomized trials were excluded. The common odds ratio was calculated for each intervention using the Mantel-Haentzel test. Homogeneity of treatment effect was evaluated using the Breslow-Day test. MAIN OUTCOME MEASURES: Pregnancy per cycle, rate of spontaneous abortion, and ovarian hyperstimulation syndrome rate. RESULTS: Eighteen trials met the above criteria. Human chorionic gonadotropin improved PRs in IVF when GnRH agonist (GnRH-a) was used (n = 151) and was superior to P (n = 352). Its benefit in all IVF cycles, however, was not established because of significant heterogeneity of treatment effect. Progesterone improved the PR in all IVF cycles (n = 457). No significant reduction in spontaneous abortion was noted with luteal support (n = 200). Ovarian hyperstimulation syndrome occurred in 5% of patients with hCG. Combination of data from trials of luteal support with other infertility therapies was not possible because of the differences in patient populations. CONCLUSIONS: The meta-analysis supports the routine use of hCG in IVF cycles using a GnRH-a. Progesterone was also beneficial for luteal phase support in IVF. For other infertility therapy, however, further research is needed to evaluate the role of luteal phase support. PMID- 8194620 TI - Cryopreservation of human prophase I oocytes collected from unstimulated follicles. AB - OBJECTIVE: To evaluate the cryopreservation of immature human oocytes obtained from unstimulated ovarian tissue. DESIGN: Immature prophase I oocytes were obtained from unstimulated follicles and were either cryopreserved or cultured as controls. Cryopreservation was performed in a programmable freezing machine using one of two protocols. Method I (n = 133) used a one-step addition of cryoprotectant followed by a slow freeze and thaw protocol. With method II (n = 95), the cryoprotectant was added in a stepwise manner with cryopreservation performed in the presence of 0.2 M sucrose followed by rapid freezing and thawing. SETTING: Basic research center at a medical school. PATIENTS: Patients undergoing oophorectomy for nonovarian pathology. MAIN OUTCOME MEASURES: Rates of survival and maturation to metaphase II were compared between control oocytes and oocytes cryopreserved with methods I and II. RESULTS: With method I, a survival rate of 15.6% was obtained with 58.3% of surviving oocytes reaching metaphase II after culture compared with 50.0% of nonfrozen control oocytes. Method II produced a survival rate of 43.3% with 27.3% maturing to metaphase II. Maturation of control oocytes for method II was 46.4%. Although the survival rate with method II was significantly higher than with method I, the rate of in vitro maturation to metaphase II showed no difference. CONCLUSIONS: These results demonstrate that human prophase I oocytes obtained from unstimulated antral follicles are capable of meiotic maturation after cryopreservation. PMID- 8194621 TI - Immunoreactive endothelin-1 concentrations in follicular fluid of women with and without endometriosis undergoing in vitro fertilization-embryo transfer. AB - OBJECTIVE: To determine the concentrations of immunoreactive (IR) endothelin-1 in human follicular fluid (FF) and whether IR-endothelin-1 levels are different in women with endometriosis-associated infertility. DESIGN: Follicular fluid and plasma samples, obtained from women with and without endometriosis undergoing IVF ET, were collected at the time of oocyte aspiration and analyzed for IR endothelin-1 levels. SETTING: Infertility clinic in an academic research environment. RESULTS: Overall, 90% of FF samples and 60% of plasma samples contained IR-endothelin-1 detectable above the threshold of assay sensitivity. Immunoreactive endothelin-1 levels (mean +/- SEM) in FF samples from women with and without endometriosis-associated infertility were 74 +/- 12 and 37 +/- 6 pg/mL, respectively. There was no difference in IR-endothelin-1 levels in FF samples between controlled ovarian hyperstimulation cycles with or without leuprolide acetate. No significant differences were detected in plasma IR endothelin-1 levels in women with endometriosis-associated infertility when compared with those without. CONCLUSIONS: These results demonstrate the presence of IR-endothelin-1 in human FF obtained at the time of oocyte aspiration for IVF ET and higher levels of IR-endothelin-1 in FF of women with endometriosis associated infertility. PMID- 8194622 TI - Outcome of donor versus husband insemination in couples with unexplained infertility treated by in vitro fertilization and embryo transfer. AB - OBJECTIVE: To examine the IVF-ET outcome of couples with unexplained infertility treated by husband versus donor sperm. DESIGN: A retrospective analysis of the IVF-ET outcome of couples with unexplained infertility treated by either husband or donor sperm and in a subgroup of patients treated simultaneously by husband and donor sperm. SETTING: IVF Unit, Serlin Maternity Hospital, Tel Aviv, Israel. PATIENTS: Couples diagnosed as having unexplained infertility underwent IVF at our Unit; included were 96 couples treated by husband insemination (group A), 27 couples who received donor insemination because of azoospermia (group B), and 8 couples who sought donor insemination after having previously failed IVF (group C). RESULTS: No statistically significant difference was found between groups A and B regarding age of the females, duration of infertility, number of IVF cycles, fertilization rate, number of ETs, and pregnancy rate. Oocytes collected in group C were subdivided further into two groups: 45 were incubated with husband sperm and 46 were incubated with donor sperm. Fertilization rates were 46.6% and 50%, respectively. One pregnancy occurred. CONCLUSION: In couples with unexplained infertility who had undergone IVF-ET with husband insemination, the fertilization and pregnancy rates were similar to those of couples who were treated by donor sperm. PMID- 8194624 TI - Selection of human spermatozoa by a hyperosmotic two-layer Percoll gradient. AB - OBJECTIVE: To investigate whether a hyperosmotic Percoll solution improves the spermatozoal recovery rate of a two-layer Percoll gradient. DESIGN: A total of 49 semen samples were prepared by both the conventional two-layer Percoll gradient and a hyperosmotic Percoll gradient. SETTING: In vitro fertilization laboratory of a tertiary care, university-affiliated hospital. PATIENTS: Semen samples were obtained from patients attending semen analysis. MAIN OUTCOME MEASURES: The number of spermatozoa recovered, percentage motility, percentage normal morphology, and their survival at 24 hours were assessed after preparation by both Percoll gradients. RESULTS: The hyperosmotic Percoll gradient resulted in a significantly higher total and motile sperm recovery rate. The degree of increase in total sperm recovery was significantly higher in abnormal semen samples compared with normal semen samples. Percentage normal morphology of sperm samples prepared by hyperosmotic Percoll was improved compared with conventional Percoll but was only significant in abnormal semen samples. However, percentage motility of sperm samples prepared by the hyperosmotic Percoll was significantly lower than those prepared by conventional Percoll gradients. CONCLUSIONS: The hyperosmotic two-layer Percoll gradient improved motile sperm recovery but also recovered more immotile sperm, leading to a decrease in percentage motility. This technique may allow us to recover more spermatozoa when we come across samples of low sperm concentration. PMID- 8194623 TI - Laparoscopic versus subinguinal varicocelectomy: a comparative study. AB - OBJECTIVE: To determine the relative advantages of the laparoscopic approach to varicocelectomy, postoperative morbidity and pain in patients undergoing subinguinal varicocelectomies were compared with that of patients undergoing laparoscopic varicocele repairs. DESIGN: Retrospective study of concurrent groups of patients undergoing laparoscopic or open subinguinal varicocele repairs. SETTING: Tertiary teaching hospital. PATIENTS: Forty-seven patients with primary or secondary infertility. INTERVENTIONS: Patients were offered a choice between a laparoscopic or open subinguinal varicocele repair. MAIN OUTCOME MEASURES: The total number of pain pills used, the number of days of analgesics, and the number of days off from work after surgery were recorded. RESULTS: Fourteen patients underwent laparoscopic varicocelectomies, and 33 patients underwent subinguinal varicocelectomies. Analgesic use by the laparoscopic patients was no different from that of the subinguinal patients. The length of time off from work was significantly longer for the laparoscopic patients (6.4 days) as compared with the time off from work for the patients who underwent subinguinal varicocele repairs (2.6 days). CONCLUSION: The subinguinal varicocele repair performed with local anesthesia is a safe, low morbid technique offering a quicker recovery period than laparoscopic approaches. Although laparoscopic repairs may offer a shorter recovery period when compared with standard inguinal varicocelectomies, this is not the case when compared with subinguinal approaches. PMID- 8194625 TI - Epithelial cell coculture and the induction of sperm capacitation. AB - OBJECTIVE: To investigate the influence of cultured human oviductal epithelial cells on the movement characteristics of human spermatozoa. DESIGN: Human spermatozoa were cultured with monolayers of human epithelial or Vero cells or conditioned media derived from these cell types. The viability and movement characteristics of the cells was subsequently analyzed at 4, 24, and 48 hours. SETTING: University hospital and Medical Research Council laboratories. PATIENTS, PARTICIPANTS: Volunteer donors. MAIN OUTCOME MEASURES: Movement characteristics of human spermatozoa. RESULTS: The presence of both Vero and oviductal epithelial cells, but not conditioned media, had a general promoting effect on sperm survival, significantly enhancing sperm viability and motility for up to 48 hours of culture. In addition, the presence of oviductal epithelial cells had a specific, significant stimulatory effect on sperm capacitation, enhancing the incidence of hyperactivated motility after 4, 24, and 48 hours of culture. Significantly, this effect was not observed with cocultures containing Vero cells. CONCLUSIONS: The coincubation of human spermatozoa with human oviductal epithelial cells provides a convenient system for the induction and analysis of sperm capacitation. PMID- 8194626 TI - Reduced semen quality caused by chronic abacterial prostatitis: an enigma or reality? AB - OBJECTIVE: To investigate whether there is an inter-relationship between chronic abacterial prostatitis and potential infertility. DESIGN: As part of the eligibility studies for hyperthermia treatment for chronic abacterial prostatitis patients, a large number of chronic prostatitis patients were referred to us from peripheral outpatient clinics. Sperm analysis was a routine portion of the eligibility studies. To exclude bacterial prostatitis, urine cultures, expressed prostatic secretion, and semen cultures were performed. The patient population was not differentiated on the basis of those suffering from either nonbacterial prostatitis or prostatodynia according to the commonly accepted classification. The control group was the laboratory normal standard group. SETTING: Normal human volunteers in an academic and clinical research environment. PATIENTS: The first group includes 86 patients suffering from long-standing (1 to 20 years) chronic abacterial prostatitis, according to the commonly accepted classification, with a mean age of 39.9 +/- 9.5 years. The second group includes 101 normal fertile men with a mean age of 31.4 +/- 5.5 years. INTERVENTIONS: The routine semen analysis performed included biochemical tests of seminal plasma, bacteriology, and light microscopy. MAIN OUTCOME MEASURE: The original hypothesis was based on a reduction in semen quality in these patients caused by chronic abacterial prostatitis. Measurements for sperm motility parameters, morphology characteristics, prostate markers, and white blood cells (WBC) were designed accordingly. RESULTS: Statistical comparisons of the two groups showed that several sperm motility parameters, morphology characteristics, prostate markers, and WBC are outside of the normal value ranges in the chronic abacterial prostatitis group. In addition, there is a correlation between the duration of the disease and two important sperm analysis variables: increased prostatic markers and appearance of sperm morphological defects. CONCLUSION: From the results obtained, the high incidence of secondary infertility in these patients may be explained. PMID- 8194627 TI - Effect of sodium nitroprusside on sperm motility, viability, and lipid peroxidation. AB - OBJECTIVE: To analyze the effect of sodium nitroprusside, a nitric oxide releaser, on sperm motion and lipid peroxidation-induced membrane damage in cryopreserved human sperm. DESIGN: Post-thaw, cryopreserved, human sperm samples were washed and divided into three aliquots. Each aliquot was incubated with either 0, 50, or 100 nM sodium nitroprusside. INTERVENTIONS: Samples were analyzed for lipid peroxidation (measured by malonaldehyde-thiobarbituric acid reactivity) at 3 hours post-thaw. MAIN OUTCOME MEASURES: Percent viability and motion parameters were assessed at 0, 10, and 30 minutes and 2, 3, 5, and 6 hours post-thaw. RESULTS: All results represent a mean +/- SEM, n = 10. Lipid peroxidation in samples incubated with 50 nM sodium nitroprusside (15.1 +/- 2.1 nM malonaldehyde/10(8) sperm) or 100 nM sodium nitroprusside (13.2 +/- 2.1 nM malonaldehyde/10(8) sperm) was significantly lower than in controls (22.7 +/- 3.1 nM malonaldehyde/10(8) sperm). Percent viability was significantly reduced from 0 minutes (60.6% +/- 3.5%) to 6 hours post-thaw in controls (38.0% +/- 5.1%) but not in 50 nM (46.8% +/- 10.4%) or 100 nM (48.8% +/- 6.5%) sodium nitroprusside treated samples. Compared with controls (18.3% +/- 3.4%), maintenance of percent motility at 3 hours post-thaw was significantly improved in 50 nM (24.5% +/- 2.9%) and in 100 nM (26.3% +/- 3.2%) sodium nitroprusside-treated samples. Straight line velocity maintenance was significantly improved in 50 nM (37.3 +/- 1.3) and in 100 nM (37.0 +/- 1) sodium nitroprusside-treated samples as compared with controls (30.5 +/- 1.7). Significant improvements in curvilinear velocity maintenance compared with controls (56.3 +/- 2.9) also were observed in 50 nM (65.9 +/- 2.1) and 100 nM (72.1 +/- 4.1) sodium nitroprusside-treated samples. Significant differences in the motion parameters of sodium nitroprusside-treated samples were maintained at 5 and 6 hours post-thaw in comparison to controls. CONCLUSION: These results suggest that sodium nitroprusside is beneficial to the maintenance of post-thaw sperm motion and viability for up to 6 hours and that reduction of lipid peroxidative damage to sperm membranes may be the mechanism for these benefits. PMID- 8194628 TI - Inhibition of angiotensin-converting enzyme--a new concept of medical treatment of male infertility? AB - OBJECTIVES: To evaluate the effectiveness of systemic captopril therapy. DESIGN: Randomized double-blind study. SETTING: Andrology Unit at the Department of Dermatology, University of Munich, Munich, Germany. PATIENTS: Infertile men suffering from oligozoospermia (5-20 x 10(6) spermatozoa/mL) and/or asthenozoospermia. INTERVENTIONS: Captopril was given orally; samples of seminal plasma were collected twice before treatment and 4 and 12 weeks after captopril administration. MAIN OUTCOME MEASURE: Semen parameters, pregnancy rate, ACE activity, and kinin levels. RESULTS: After 4 weeks of therapy, significant differences between verum group and placebo group were found concerning ACE activity and kinin levels. Sperm density improved significantly after 12 weeks of captopril therapy. All other semen parameters remained unchanged. The pregnancy rate was not improved. CONCLUSIONS: The suitability of captopril in the therapy of oligozoospermia and/or asthenozoospermia for improvement of male infertility seems to be limited. PMID- 8194629 TI - The sequential effects of human cervical mucus, oviductal fluid, and follicular fluid on sperm function. AB - OBJECTIVE: To compare the sequential effects of human cervical mucus (CM), oviductal fluid, and follicular fluid (FF) on sperm motility, hyperactivation, and the acrosome reaction during 9 hours of incubation in vitro. DESIGN: Spermatozoa from a fertile donor were allowed to penetrate human CM in vitro and then were recovered and incubated in either 30% human oviductal fluid or a simple salt solution for 3 hours before challenge with 20% FF. Thus, the sequential effects of the fluids collected from the female reproductive tract on sperm hyperactivation and acrosome reaction were examined. SETTING: The donor insemination program at the University Clinic within the Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: All donors used in this study were involved in the donor insemination program. MAIN OUTCOME MEASURES: Sperm motility, hyperactivation, and percentage of acrosome-reacted spermatozoa were measured. RESULTS: This study used an in vitro technique to mimic sperm transport in vivo. Spermatozoa sequentially incubated with female reproductive tract secretions in vitro showed a maintenance in the level of FF-induced hyperactivated motility and a decreased response to the FF-induced acrosome reaction when compared with sperm challenged with FF in the absence of prior incubation with human oviductal fluid. CONCLUSION: It is suggested that human oviductal fluid may serve to delay the FF-induced acrosome reaction. PMID- 8194631 TI - The reduction of postoperative adhesions by two different barrier methods versus control in cynomolgus monkeys: a prospective, randomized, crossover study. AB - OBJECTIVES: To determine the effectiveness of two different surgical membranes in preventing postoperative adhesions as compared with control and to evaluate the benefit as compared with "second-look" adhesiolysis. DESIGN: A randomized, prospective, crossover study. SETTING: A colony of individually caged non-human primates, Department of Obstetrics and Gynecology, Eastern Virginia Medical School Norfolk, Virginia. INTERVENTIONS: Hysterotomy or adhesiolysis at the time of exploratory laparotomy, with subsequent scoring of adhesions based on area, vascularity, tenacity, and adhesion score. RESULTS: The combined crossover data reveal that both surgical barriers are superior in adhesion prevention to microsurgical technique alone. Expanded polytetrafluoroethylene (Gore-Tex Surgical Membrane; WL Gore and Associates, Flagstaff, AZ) was better than oxidized regenerated cellulose (Interceed; Johnson and Johnson Medical, Inc., Arlington, TX) with respect to adhesion area, tenacity, and vascularity, with a significant improvement in the total adhesion score. Second-look adhesiolysis resulted in significant adhesion reduction in the control group, making second look adhesiolysis statistically similar to the use of either barrier alone (without subsequent adhesiolysis). Gore-Tex removal does not result in adhesion formation as determined by third-look surgery. CONCLUSIONS: Both Interceed and Gore-Tex show a reduction in the prevention of postsurgical adhesions after hysterotomy incisions, as compared with microsurgical technique alone. Second look adhesiolysis is as effective as either barrier in the reduction of permanent pelvic adhesions. PMID- 8194630 TI - Interleukin 10: ability to minimize postoperative intraperitoneal adhesion formation in a murine model. AB - OBJECTIVE: To determine the ability of interleukin 10 (IL-10) to suppress postoperative intraperitoneal adhesion formation. DESIGN: Randomized, controlled trial. SETTING: University animal research facility. ANIMALS: Six-week-old Swiss Webster mice undergoing a standardized intraperitoneal operative procedure. INTERVENTIONS: Animals were randomized to "surgery" or "no surgery" and then further randomized to receive intraperitoneal injections of 1 mL phosphate buffered saline (PBS) or 1 microgram/kg IL-10 in 1 mL PBS. Vehicle-only doses were given immediately after surgery and then every 24 hours for a total of four injections. Interleukin 10 injections were similarly given but with an added preoperative injection 30 minutes before surgery in one half of the animals. MAIN OUTCOME MEASURE: Adhesion formation. RESULTS: Animals treated with vehicle or IL 10 but not undergoing surgical intervention had no intraperitoneal adhesions. Animals undergoing surgery who were treated with IL-10, with or without a preoperative dose, had significantly lower postoperative adhesion scores than did control animals who postoperatively received PBS only. CONCLUSION: Interleukin-10 is effective at limiting postoperative intraperitoneal adhesion formation with minimal evident systemic side effects. PMID- 8194633 TI - Factors predicting outcome in 215 consecutive thawed embryo replacements. AB - This retrospective study was undertaken to determine which factors were associated with outcome in thawed embryo replacement cycles. The number of embryos replaced and the response to exogenous ovarian stimulation in the original IVF cycle were significantly associated with the conception rate. PMID- 8194632 TI - Steroid reduction during ovarian stimulation impairs oocyte fertilization, but not folliculogenesis, in rhesus monkeys. AB - OBJECTIVE: To test the hypothesis that steroids locally modulate and may be required for normal follicular function and gametogenesis in primates, the effects of steroid reduction during gonadotropin-stimulated folliculogenesis was studied in rhesus monkeys. DESIGN: Animals received human FSH (hFSH; days 1 to 6) and hFSH+human LH (hLH; day 7) to promote multiple follicular growth, and then received hCG (day 8) for ovulatory maturation. Four animals received trilostane (3 beta-hydroxysteroid dehydrogenase inhibitor) on days 1 to 8 or no inhibitor (controls; n = 4). Follicles were aspirated 34 hours after hCG. MAIN OUTCOME MEASURES: Follicular growth, serum E2, P, and pregnenolone, oocyte nuclear maturity, and IVF. RESULTS: Trilostane markedly reduced E2 to levels as low as 7% of controls throughout the follicular phase. Pregnenolone was 66-fold greater during trilostane treatment relative to controls. In both groups, P was at baseline during follicular stimulation but was reduced for 72 hours after hCG in trilostane-treated animals. Despite E2 suppression, follicular growth and oocyte nuclear maturity were unaltered by trilostane. Trilostane hindered the fertilizability of metaphase II oocytes (15%) in three of four animals compared with controls (65%). Metaphase I oocytes that required > 8 hours to complete meiosis in vitro failed to fertilize in the same three of four receiving trilostane relative to controls (31%). CONCLUSIONS: Follicular growth and oocyte meiosis did not require high or increasing E2 levels. Levels of follicular products other than E2 may be of value in determining the progress of ovarian stimulation protocols. However, the acquisition of oocyte competence for fertilization may require steroids. PMID- 8194634 TI - Controlled ovarian hyperstimulation: an adjunct to assisted reproductive technology. AB - Controlled ovarian hyperstimulation was given to a study group consisting of male factor, endometriosis, and unexplained infertility. The aim of the study was to determine whether COH might be of value for such couples in a setting lacking ART facilities. When compared with their own spontaneous cycles or with a control group (untreated but scanned), COH proved significantly better for unexplained infertility. However, COH was not significantly effective for male factor infertility. This study shows that COH should be offered routinely in general hospitals to couples on long-term waiting lists for ART (especially those facing enforced expectant management). PMID- 8194635 TI - Laparoscopic removal of twin cornual pregnancy after in vitro fertilization. AB - The laparoscopic management of tubal pregnancies by salpingostomy has become a clinical standard of care (5). Those surgeries usually are performed for tubal pregnancies that are located distally to the cornua and the intramural piece of the tube. We previously reported on the conservative surgical management of interstitial pregnancies (3). To our knowledge, cornual pregnancies have never before been approached laparoscopically. Such a surgical approach is reported here, involving a twin gestation in the left uterine cornua conceived by IVF in a women with bilaterally absent tubes. PMID- 8194636 TI - Pregnancy after laparoscopic neosalpingostomy in a patient with atresia of the distal fallopian tubes. AB - Structural congenital anomalies of the fallopian tube are interesting clinical problems that are infrequently reported in the literature. We report a patient with congenital absence of the distal fallopian tubes. After surgical correction by laparoscopic neosalpingostomies using a new intussusception technique, a normal IUP occurred and was delivered at term. PMID- 8194637 TI - Familial adenomyosis: a case report. AB - The persuasive data not only illustrate a familial tendency towards adenomyosis but also emphasize that adenomyosis can be diagnosed noninvasively and accurately by MRI. A possible familial predisposition toward or a direct familial cause of adenomyosis warrants further investigation. PMID- 8194638 TI - Marginally elevated prolactin levels require magnetic resonance imaging and evaluation for acromegaly. AB - Marginal elevations in serum PRL concentration represent a particularly difficult diagnostic dilemma. In most cases, mild hyperprolactinemia is not associated with organic disease. Patients with menstrual disturbances, galactorrhea, and confirmed elevations in serum PRL should have a screening TSH to rule out primary hypothyroidism (5). In cases where there is no clear etiology of hyperprolactinemia, an MRI should be performed. Magnetic resonance imaging with gadolinium is more sensitive and specific than CT scanning in detecting all types of pituitary tumors and is the study of choice (4). Further, a serum IGF-1 level (or OGTT) should be obtained when clinical symptoms and/or a pituitary mass suggest the possibility of acromegaly. An individual with abnormal GH screening tests but an unremarkable MRI would be subjected to an especially careful follow up, including IGF-1 and PRL levels every 6 to 12 months. In this way, early tumor growth may be detected making a surgical cure more likely (Fig. 1). Although we have stressed the importance of GH-producing tumors as a cause of hyperprolactinemia, other tumor types of the pituitary may do so as well. Most of these will be detected by MRI. PMID- 8194639 TI - The effect of a surgical lubricant on in vivo sperm penetration of cervical mucus. AB - The implications of these data is that coital lubricants may impair fertility of some couples. Unfortunately, conception was not an end point on this study, and our conclusions must be considered inferential. Nevertheless, the results from this study lead us to recommend avoidance of surgical lubricants by couples attempting pregnancy. PMID- 8194640 TI - Differences in seminal parameters in specimens collected via intercourse and incomplete intercourse (coitus interruptus) AB - Whatever the mechanism of such improvements may be, the results in this study point out that coitus interruptus in the human may not be the method of choice for collection of semen specimens, especially in patients with spermatogenic dysfunctions such as hypospermia, oligospermia, and asthenospermia. It should also be noted at this point that, for whatever purpose (semen analysis or artificial insemination by husband), the collected specimen should as closely as possible resemble the ejaculate delivered during intercourse. The complete coitus method, as applied in this study, showed that completion of the ejaculatory process during intercourse as compared with the coitus interruptus method, may assist in the improvement of the collected specimen and should closely resemble the ejaculate obtained during intercourse without the use of Silastic condoms. Furthermore, on the basis of the results generated in this study, the complete coitus method should always be the method of choice for male infertility patients with ejaculatory and spermatogenic dysfunctions as well as for scientists and clinicians who deal in the field of infertility diagnosis and treatment. PMID- 8194641 TI - Blunt trocar laparoscopy. AB - A technique, termed blunt trocar laparoscopy, has been developed to avoid the use of both Veress needles and sharp primary trocars and to avoid carbon dioxide leakage without the use of fascial sutures. To evaluate this technique's effectiveness, the time required and the length of the skin incision was evaluated prospectively in 33 consecutive unselected patients and the results were compared with the patient's BMI. The blunt trocar technique took 3.5 +/- 1.3 minutes (mean +/- SD) to perform and the average incision length was 14 +/- 2 mm. Although the time of the procedure increased slightly with the BMI, even in the obese patients (BMI > 30 kg/m2; n = 10), the average time for the procedure was only 4.0 +/- 1.6 minutes. No carbon dioxide leakage or complications occurred in any patient. The results of this study indicate that a blunt trocar technique may be a useful and relatively quick alternative approach for laparoscopy. PMID- 8194642 TI - Sex selection--on trial again? PMID- 8194643 TI - Lactic dehydrogenase-C4 activity marker of germinal activity? PMID- 8194644 TI - Fetal heart rate decelerations and umbilical cord blood gas values. AB - Although fetal heart rate (FHR) monitoring is widely used for fetal surveillance, there is still disagreement about the value of cardiotocography and the interpretation of FHR patterns. We addressed this in a prospective study in which umbilical cord blood gas and pH values at the time of cesarean section were related to different FHR patterns classified prior to surgery. The patient population consisted of 56 pregnant women with singleton fetuses of gestational age between 37 and 43 weeks. Indication for cesarean section was late FHR decelerations in 16 cases and variable decelerations in 17. Twenty-three patients operated on electively, and without any FHR abnormalities, served as a reference group. Late FHR decelerations were associated with the lowest pH and PO2 levels in arterial as well as in venous blood. In the group with variable decelerations, the umbilical vein PO2 was similar to that of the reference group, whereas the PO2 value in the artery was significantly lower. Hence, in this clinical study a clear relationship was found between the different FHR patterns and changes in the acid-base balance. PMID- 8194645 TI - Multivariate analysis of determinants of fetal growth retardation. AB - OBJECTIVE: To analyse the relative effect of the risk factors related to fetal growth retardation (FGR) in the central area of Spain. STUDY DESIGN: This is a case-control survey of 370 full-term gestations. Of the 370 women, 185 were diagnosed with intrauterine growth retardation, and 185 were in the normal group. All came from a central region of Spain. We took into account 25 possible risk factors. RESULTS: In the FGR group we found 12 risk factors with statistical significance in the univariate analysis (tobacco, drugs, low pre-pregnancy weight, low maternal height, little gestational weight gain, excessive physical activity during pregnancy, low socioeconomic status, low educational level, unmarried, urinary infection, mother's haematological changes, and previous infertility). After the multiple logistic regression analysis, five factors were shown to exist as independent risks (tobacco: OR, 23.50; 95% CI, 3.01-183.18; P < 0.01; low pre-pregnancy weight: OR, 4.01; 95% CI, 2.14-7.51; P < 0.001; low socioeconomic status: OR, 2.91; 95% CI, 1.72-4.90; P < 0.001; little gestational weight gain: OR, 2.52; 95% CI, 1.21-5.22; P < 0.05; and urinary infection: OR, 3.83; 95% CI, 1.49-9.87; P < 0.01). CONCLUSIONS: (i) Tobacco, low pre-pregnancy weight and low socioeconomic status are the three main cause-effect factors of relative importance in our sanitary zone for FGR. (ii) Disproportionate FGR is related more to older mothers and maternal previous illness than to the proportionate FRG. PMID- 8194646 TI - Absent end diastolic flow of umbilical artery Doppler: pregnancy outcome in 62 cases. AB - We retrospectively studied the outcome of pregnancy in 62 cases of absent end diastolic flow (AEDF) of umbilical artery Doppler flow velocity waveform. The history of pregnancies revealed that nearly all were of high risk. Many cases presented cerebral (65%) or uterine (55.5%) Doppler flow abnormalities, or both (38%). We noted 10 fetal deaths and decided 7 pregnancy terminations. Malformation and chromosomal defect rate was 16%. We noted 44 (71%) live-births, a very high rate of cesarean section (86%), prematurity (75%), small for gestational age (39%). Forty-five percent of the neonates had a 1-min Apgar score under 7, which dropped to 27% at 5 min. Neonate mortality rate was 6.9% and the total mortality rate was 34% (21/62). Morbidity was significant (7 cases with severe morbidity, 2 cases with chromosomal abnormality of poor prognosis). We compared different sub-groups with a view to looking for some prenatal factors which predict poor neonatal outcome in case of AEDF. PMID- 8194647 TI - Comparison between the Joel-Cohen and Pfannenstiel incisions in cesarean section. AB - Most surgeons adopt the Joel-Cohen method for opening the abdomen once they have become familiar with it. We present here, for the first time, a study comparing the post-operative outcome between the Joel-Cohen and the Pfannenstiel methods for opening the abdomen in cesarean section. PMID- 8194648 TI - Ultrasound assessment of cervical dynamics during the first stage of labor. AB - OBJECTIVE: Assessment of cervical dynamics during the first stage of labor by a combination of ultrasound cervimetry and intrauterine tocography. METHODS: Sixty two parturients were divided into four groups: nulliparous women in spontaneous (n = 9) or oxytocin-induced labor (n = 26), parous women in spontaneous (n = 11) or oxytocin-induced labor (n = 16). Intrauterine pressure and cervical dilatation were continuously recorded and assessed by off-line computer analysis. RESULTS: All women with spontaneous labor showed cervical responses to uterine contractions at the beginning of the recording. The first cervical response to a uterine contraction occurred at a significantly smaller dilatation in parous than in nulliparous women with induced labor (2.9 and 3.6 cm, respectively). Also, acceleration of cervical dilatation occurred at less dilatation in parous than in nulliparous women (3.4 cm and 4.8 cm, respectively), and myometrial work per cm of cervical dilatation was less in parous than in nulliparous parturients. CONCLUSIONS: The results indicate significant differences between cervical dilatation patterns in nulliparous and parous women, which may be due to structural cervical changes caused by labor and parturition. The labor patterns found were different from those originally described by Friedman (Friedman EA. Graphic analysis of labor. Am J Obstet Gynecol 1954; 68: 1568-1575), as no deceleration phases were detected. Ultrasound cervimetry is a valuable technique for the study of cervical dynamics during labor. PMID- 8194649 TI - Social class, ethnicity and other risk factors for small for gestational age and preterm delivery in The Netherlands. AB - Social class and ethnicity are important risk factors for small-for-gestational age and preterm delivery in many countries. This study was performed to assess whether this is also the case in the Netherlands, a country with a high level of social security, relatively small income differences and easy access to medical care for all its inhabitants. Other risk factors that were taken into account were smoking, drinking, occupation, age and height. Information was collected by interview in the first 3 weeks of life of the mothers of 2027 (response 97%) live born singletons born in the period from April 1988 to October 1989 in the study area. After adjustment for possible confounding factors very low social class, compared with high social class, was significantly associated with reduced birthweight (-4.0%; 95% CI, -7.4% to -0.7%), but not with preterm delivery (OR, 2.09; 95% CI, 0.67-6.48). The adjusted birthweight of Turkish infants (2.7%; 95% CI, -1.1% to 6.5%) and the adjusted birthweight of infants from Suriname or the Antilles (-1.6%; 95% CI, -5.5% to 2.1%) were not significantly different compared with infants of Dutch mothers. After adjustment, the frequency of preterm birth was lower in Turkish infants, but not significantly (OR, 0.22; 95% CI, 0.04 1.10), whereas the frequency of preterm birth in infants from Suriname or the Antilles was significantly higher (OR, 2.51; 95% CI, 1.04-6.08) compared with Dutch infants. Of the other factors the main risk factors were smoking (negatively related with birth-weight) and maternal age(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194650 TI - Pseudolymphoma of the nipple. AB - Pseudolymphoma of the breast is a rare benign disorder. To avoid over-treatment or misdiagnosis of a malignancy of the breast, exact histological diagnosis is important. We report on a 69-year-old patient, who presented with symptoms of mastitis. PMID- 8194651 TI - Shoulder dystocia and symphysiotomy: a case report. AB - Symphysiotomy in a case of severe shoulder dystocia resulted in a successful vaginal delivery. Maternal morbidity, however, was considerable. PMID- 8194652 TI - Hyperreactio luteinalis associated with non-immune hydrops fetalis--the role of pituitary hormones. AB - The level of pituitary hormones was measured in the serum and cysts' aspirate in a case of hyperreactio luteinalis (HL) complicating non-immune hydrops fetalis. The level of follicular stimulating hormone (FSH), prolactin and growth hormone (GH) was within normal range for pregnancy in both the serum and cysts' aspirate. The importance of increased luteinizing hormone (LH) level which was demonstrated in the cysts' fluid should further be determined. PMID- 8194653 TI - Primary prevention of neural-tube defects with folic acid. AB - This symposium dealt with the trilogic, epidemiologic, occupational, genetic and nutritional aspects of neural tube defects (NTD). Homocysteine could be involved in the pathogenesis of NTD. Folic acid is highly recommended for prevention. PMID- 8194654 TI - Hysteroscopy: the state of the art. PMID- 8194655 TI - Postmenopausal hormone replacement therapy--clinical implications. AB - The menopause is defined as cessation of menstruation, ending the fertile period. The hormonal changes are a decrease in progesterone level, followed by a marked decrease in estrogen production. Symptoms associated with these hormonal changes may advocate for hormonal replacement therapy. This review is based on the English-language literature on the effect of estrogen therapy and estrogen plus progestin therapy on postmenopausal women. The advantages of hormone replacement therapy are regulation of dysfunctional uterine bleeding, relief of hot flushes, and prevention of atrophic changes in the urogenital tract. Women at risk of osteoporosis will benefit from hormone replacement therapy. The treatment should start as soon after menopause as possible and it is possible that it should be maintained for life. The treatment may be supplemented with extra calcium intake, vitamin D, and maybe calcitonin. Physical activity should be promoted, and cigarette smoking reduced if possible. Women at risk of cardiovascular disease will also benefit from hormone replacement therapy. There is overwhelming evidence that hormone therapy will protect against both coronary heart disease and stroke, and there is no increased risk of venous thrombosis or hypertension. A disadvantage of hormone replacement therapy is an increased risk of forming gall-bladder stones and undergoing cholecystectomy. Unopposed estrogen therapy gives a higher incidence of endometrial cancer in women with an intact uterus, but the contribution of progestins for about 10 days every month excludes this risk. Breast cancer in relation to estrogen-progestogen therapy has been given much concern, and the problem is still not fully solved. If there is a risk, it is small, and only after prolonged use of estrogen (15-20 years). The decision whether or not to use hormone replacement therapy should, of course, be taken by the individual woman in question, but her decision should be based on the available scientific information. It is the opinion of the authors that the advantages of hormone replacement therapy far exceed the disadvantages. We suggest that every woman showing any signs of hormone deprivation should be treated with hormone replacement therapy. This includes women with subjective or objective vaso-motor symptoms, genito-urinary symptoms, women at risk of osteoporosis (fast bone losers), and women at risk of cardiovascular diseases. PMID- 8194656 TI - The association of primiparity with intrauterine growth retardation. AB - The role of parity in the epidemiology of intrauterine growth retardation (IUGR) is not well understood, as some risk factors for IUGR are associated with young age and primiparity, and some are more frequent among older multiparous women. This paper examines the unique role of primiparity in the etiology of IUGR in a series of 25,614 singleton births in the southern part of Israel. The rates of IUGR were 3.5% among primiparae and 1.7% in multiparae. (Risk ratio = 1.99; 95% confidence interval, 1.69-2.35). Maternal age was associated with IUGR only among primiparae but not in multiparae. Of the obstetric factors examined, the following were found to be significantly associated with IUGR: hypertension, prior infertility, oligohydramnios, gross fetal congenital anomalies, and being a female fetus. After simultaneous adjustment for these risk factors by multiple logistic regression analysis, the odds ratio associated with parity was 1.62 (95% confidence interval, 1.30-2.01), suggesting that primiparity constitutes an independent risk factor for IUGR. PMID- 8194657 TI - Insulin resistance or insulin deficiency. Which is the primary cause of NIDDM? PMID- 8194658 TI - GAD antibody negative NIDDM in adult black subjects with diabetic ketoacidosis and increased frequency of human leukocyte antigen DR3 and DR4. Flatbush diabetes. AB - The objective of this study is to understand the metabolic and immunologic basis of diabetes in adult blacks with diabetic ketoacidosis (DKA). Twenty-one black adults presenting with DKA ([mean +/- SD] blood pH = 7.18 +/- 0.09, plasma glucose = 693 +/- 208 mg/dl, and positive serum ketones) had a subsequent clinical course of non-insulin-dependent diabetes mellitus (NIDDM). Human leukocyte antigens (HLAs) DR and DQ and antibodies to glutamic acid decarboxylase (GAD) and islet cell cytoplasmic proteins (ICP) were measured to assess autoimmunity. Insulin action was evaluated by the euglycemic insulin clamp, and insulin secretion was measured by C-peptide responses to oral glucose. Ketoacidosis was treated with insulin. Two subjects had a precipitating illness; four had a history of NIDDM. At the time of study, subjects' glycemic control was good (HbA1c = 5.7 +/- 1.6%). Nine subjects were treated with insulin, and 12 were on either sulfonylurea treatment or diet alone. Men (n = 12) were younger than women (n = 9) (40.8 +/- 9.8 and 51.1 +/- 6.3 years of age, respectively, P < 0.05) but similar in body mass index (27.8 +/- 2.7 and 29.98 +/- 4.1 kg/m2, respectively). Antibodies to GAD and ICP were absent. All but one subject was insulin resistant compared with normal subjects (glucose disposal 3.56 +/- 0.04 vs. 6.86 +/- 0.02 mg.kg-1.min-1), and insulin secretion was lower. HLA DR3 and DR4 frequency was higher than in nondiabetic black control subjects (65 vs. 30%, P < 0.012).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194659 TI - Human glucagon-like peptide-1 receptor gene in NIDDM. Identification and use of simple sequence repeat polymorphisms in genetic analysis. AB - Glucagon-like polypeptides, GLP-1-(7-36)-amide and GLP-1-(7-37), are important regulators of insulin synthesis and secretion by islet beta-cells. The hypothesis to be tested in this study was that defects in the islet beta-cell GLP-1 receptor gene contribute to the impaired glucose-regulated insulin secretion of non insulin-dependent diabetes mellitus (NIDDM). Human islet GLP-1 receptor genomic clones were isolated, and two highly polymorphic simple sequence repeat regions (GLP-1R-CA1 and GLP-1R-CA3) were identified. Polymerase chain reaction assays were developed to define alleles. For GLP-1R-CA1, 14 alleles were observed in African-Americans (heterozygosity [het] = 0.78) and 6 alleles in Caucasians (het = 0.67). For GLP-1R-CA3, 16 alleles were observed in African Americans (het = 0.89) and 8 alleles in Caucasians (het = 0.83). By genotyping all members of the 40 reference Centre d'Etude du Polymorphisme Humain pedigrees at GLP-1R-CA3, the human GLP-1 receptor gene was uniquely placed on chromosome 6p between GLO1 and D6S19, 20.4 cM from human leukocyte antigen. To assess the possible role of the GLP-1 receptor gene in determining the genetic susceptibility to NIDDM, allelic frequencies of GLP-1R-CA1 and GLP-1R-CA3 were compared between African-American NIDDM patients (n = 95) and control subjects (n = 93). The frequencies did not differ between the two groups at either GLP-1R-CA1 or GLP-1R-CA3. The GLP-1 receptor gene simple-sequence repeat polymorphisms were used for linkage analysis in Utah Mormon pedigrees (n = 16) with NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194660 TI - The effect of aminoguanidine and tolrestat on glucose toxicity in bovine retinal capillary pericytes. AB - Cultured bovine retinal capillary pericytes (BRP) were used to investigate the effect of an aldose reductase inhibitor, tolrestat, and an inhibitor of advanced glycation end products (AGE) formation, aminoguanidine, on glucose toxicity. Glucose at high concentration reduced the replicative activity of pericytes in a dose-dependent manner. Tolrestat completely inhibited the production of sorbitol in cells exposed to a high concentration of glucose but failed to protect the cells from glucose toxicity. These results suggest that sorbitol accumulation in cells is probably not the major mechanism for glucose toxicity. In contrast, the addition of aminoguanidine at 10 mM concentration to the culture media protected pericytes from glucose toxicity. The degree of protected pericytes from glucose toxicity. The degree of protection was dose-dependent and evident at aminoguanidine concentration as low as 1 mM. The drug was only slightly toxic to BRP but induced morphological changes in pericytes with the loss of cellular processes and decreased cell spreading. This may suggest some action of aminoguanidine on the pericyte cytoskeleton. High concentration of glucose significantly increased the level of early glycation but not fluorescent AGE formation on BRP proteins. This was inhibited by the addition of aminoguanidine suggesting that glycation of cellular/membrane proteins and other mechanisms may play an important role in the toxic action of high glucose levels in cultured pericytes. PMID- 8194661 TI - Intracerebroventricular administration of neuropeptide Y to normal rats has divergent effects on glucose utilization by adipose tissue and skeletal muscle. AB - Given that several genetically obese rodents characterized by hyperphagia, hyperinsulinemia, and insulin resistance have increased hypothalamic neuropeptide Y (NPY) mRNA and peptide content, the impact of NPY administered intracerebroventricularly (i.c.v.) for 7 days to normal, awake rats was investigated. NPY produced marked hyperphagia, increased body weight gain, increased basal insulinemia, and, more importantly, a much greater insulin response to meal feeding than that of saline-infused controls. NPY administration also resulted in a pronounced increase in the in vivo insulin-stimulated glucose uptake by adipose tissue but in a marked decrease in uptake by eight different muscle types. Increased insulin responsiveness of the glucose transport process by adipose tissue was accompanied by increases in both GLUT4 mRNA and protein levels. In contrast, the decreased insulin responsiveness of glucose uptake in muscles from NPY-administered rats was not related to GLUT4 expression. We conclude that i.c.v. NPY administration to normal rats produces a hormonal metabolic situation that is similar to that reported in the dynamic phase of the genetic obesity of the fa/fa strain. Thus, NPY could be of primary importance in the establishment of obesity syndromes with incipient insulin resistance. PMID- 8194662 TI - Nicotinamide prevents interleukin-1 effects on accumulated insulin release and nitric oxide production in rat islets of Langerhans. AB - Nicotinamide (NA) prevents macrophage- and interleukin-1 (IL-1)-mediated beta cell damage in vitro as well as diabetes development in animal models of insulin dependent diabetes mellitus (IDDM). IL-1 beta-mediated inhibition of insulin release and damage to beta-cells are associated with intracellular production of nitric oxide (NO) radicals. Therefore, we studied whether NA prevented IL-1 beta induced islet NO production, measured as nitrite release from isolated rat islets, and, if so, whether this action was associated with prevention of IL-1 beta-mediated inhibition of insulin release. NA dose- and time-dependently inhibited and delayed IL-1 beta-induced islet NO production. Light microscopy detected that 25 mM of NA protected against IL-1 beta-induced islet damage. Five to 50 mM of NA dose-dependently reduced inhibition of accumulated islet insulin release induced by 150 pg/ml of IL-1 beta. NA was not able to reverse the reduced ability of IL-1 beta-treated islets to respond to an acute glucose challenge. NO or nitrite did not interact directly with NA, because NA did not reduce sodium nitroprusside-generated nitrite. No-synthase inhibition with L-arginine depletion abolished NO production but only partially reduced IL-1 beta-induced inhibition of accumulated insulin release. Complete inhibition of IL-1 beta effects could not be obtained by adding L-arginine analogues to L-arginine-depleted medium, indicating that an NO-independent action of IL-1 beta on islet insulin release may exist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194663 TI - Effect of 15-deoxyspergualin on immediate function and long-term survival of transplanted islets in murine recipients of a marginal islet mass. AB - 15-Deoxyspergualin (DSG), a macrophage immunomodulatory agent, was used as a probe in a murine model of islet transplantation to examine 1) the significance of the nonspecific, macrophage-mediated effector arm of beta-cell injury in recipients of a marginal mass of isologous islets by analyzing the duration of temporary posttransplant hyperglycemia, a parameter of immediate beta-cell function; and 2) whether long-term (> 100 days) functional survival could be achieved in recipients of a marginal mass of allogeneic islets. A dose-response study of the number of islets required to ameliorate diabetes showed that 150 isologous islets per recipient resulted in a 75% incidence of cure at a mean of 39.2 +/- 5.8 days posttransplant. DSG-treated (0.625 mg.kg-1.day-1 intraperitoneally) recipients of isologous islets demonstrated a significant (P < 0.01) reduction in the duration of temporary posttransplant hyperglycemia (16.8 +/- 3.2 vs. 39.2 +/- 5.8 days), and DSG-treated recipients of allogeneic islets demonstrated a significant (P < 0.03) improvement in the rate of achieving long term functional survival (75 vs. 22% in untreated control animals). Finally, identical rates of islet engraftment were found among control animals and DSG treated animals by measurement of tissue insulin content in transplanted specimens. The results are consistent with the hypothesis that DSG alters the duration of temporary posttransplant hyperglycemia and extends long-term functional survival in murine recipients of a marginal mass of islets, not by affecting the efficiency of islet engraftment, but by suppression of the inhibitory effects on beta-cell function by nonspecific, macrophage mediators. PMID- 8194664 TI - Molecular model of human beta-cell glucokinase built by analogy to the crystal structure of yeast hexokinase B. AB - Recent studies have shown that mutations in human beta-cell glucokinase that impair the activity of this key regulatory enzyme of glycolysis can cause early onset non-insulin-dependent diabetes mellitus (NIDDM). The amino acid sequence of human glucokinase has 31% identity with yeast hexokinase, a related enzyme for which the crystal structure has been determined. This homology has allowed us to model the three-dimensional structure of human glucokinase by analogy to the crystal structure of yeast hexokinase B. This model of human glucokinase provides a basis for understanding the effects of mutations on its enzymatic activity. Residues in the active site and on the surface of the binding cleft for glucose are highly conserved in both enzymes. Regions far from the active site are predicted to differ in conformation, and 10 insertions or deletions that range in size from 1 to 7 residues are located on the protein surface between elements of secondary structure. The model structure suggests that human glucokinase binds glucose in a similar manner to yeast hexokinase. The glucose-binding site contains a conserved aspartic acid, two conserved glutamic acids, and two conserved asparagines that form hydrogen bond interactions with the hydroxyls of the glucose similar to those observed in other sugar-binding proteins. Mutation of residues in the predicted glucose-binding site has been found to greatly reduce enzymatic activity. This model will be useful for future structure/function studies of glucokinase. PMID- 8194665 TI - cAMP-independent synergistic effects of insulin and dexamethasone on fructose 2,6 bisphosphate metabolism in H4IIE cells. AB - Hormonal regulation of fructose 2,6-bisphosphate (Fru-2,6-P2) content was studied in H4IIE cells. These cells were found to be very sensitive to physiological concentrations of insulin. Addition of either insulin or dexamethasone alone increased Fru-2,6-P2 in a time- and dose-dependent manner, and the maximal effect of the hormones was seen at 1 h. Neither hormone had any measurable effect on cAMP levels. The effect of addition of both insulin and dexamethasone on Fru-2,6 P2 was synergistic. Insulin, but not dexamethasone, rapidly increased 6 phosphofructo-2-kinase (6PF-2-K) activity by causing dephosphorylation of the enzyme as judged by a decrease in the Km for fructose-6-phosphate. Addition of both hormones also resulted in a synergistic 10-fold increase in enzyme protein as measured by kinase activity and phosphoenzyme formation. Dexamethasone increased liver 6PF-2-K/Fru-2,6-P2 mRNA abundance by 10- to 12-fold as measured by a ribonuclease protection assay, and insulin increased it by only 4-fold. Effects were observed as early as 1 h after hormone addition, but addition of both hormones together showed no synergy. We conclude that the synergistic effects of insulin and dexamethasone on Fru-2,6-P2 content are mediated by a combination of stimulation of expression of the bifunctional enzyme gene by both hormones and insulin-induced modulation of the activation state of the bifunctional enzyme, both of which are mediated by cAMP-independent mechanisms. PMID- 8194666 TI - Chromosome 4q locus associated with insulin resistance in Pima Indians. Studies in three European NIDDM populations. AB - Markers on chromosome 4q have recently been shown to be associated with insulin resistance in Pima Indians, a population in which insulin resistance precedes and predicts the development of non-insulin-dependent diabetes mellitus (NIDDM). To examine whether genes in this region could play a major role in susceptibility to NIDDM in other populations, we have examined the allele frequencies of a trinucleotide repeat near the fatty acid-binding protein 2 (FABP2) gene on 4q28 31 in three European populations: Finnish, U.K. Caucasian, and Welsh. The U.K. NIDDM population was selected for insulin resistance by studying patients whose obesity-corrected fasting plasma insulin before treatment was above the 98th percentile. Seven alleles were detected. On cross-tabulation analysis, there were no significant associations between allele frequencies and glucose intolerance in any of the populations. Log-linear analysis of the results from all three populations suggested a moderately significant interaction of glucose tolerance status (normal versus diabetic) and the FABP2 allele (partial chi 2 = 24, df 6, P = 0.027). The parameter describing the interaction of allele A3 and glucose tolerance status was the only such parameter differing significantly from zero (z score +2.003, P = 0.046). In both the Finnish and U.K. population, the A3 allele was found approximately twice as frequently in NIDDM than in control subjects (Finnish control subjects, impaired glucose tolerance, and NIDDM: 12.2, 22.4, and 26.6%, respectively; U.K. control subjects and NIDDM: 7.8 and 14.6%, respectively). In the Finnish populations, no associations were found between FABP2 alleles and plasma insulin levels or with homeostatic model assessment (HOMA) estimates of beta-cell function and insulin sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194667 TI - Increased skeletal muscle capillary density precedes diabetes development in men with impaired glucose tolerance. A 15-year follow-up. AB - Gastrocnemius muscle morphology, metabolic potential, and capillarization were analyzed in 48-year-old men with regard to subsequent development of non-insulin dependent diabetes mellitus (NIDDM) in 29 subjects with impaired glucose tolerance (IGT) and in 38 control subjects. Over a 15-year period, although participating in an intervention program, 13 of the IGT subjects developed diabetes, but none of the control subjects developed diabetes. In view of their poor aerobic capacity, lack of physical fitness, and reduced glycolytic and oxidative enzymes, these 13 subjects manifested an unexpectedly high number of capillaries around all types of muscle fibers, especially type IIb fibers, as predictors of their progression to diabetes. Moreover, the number of capillaries per muscle fiber and the 2-h insulin value in the oral glucose tolerance test were highly correlated (r = 0.82, P < 0.005), whereas no correlation was found among IGT subjects who remained nondiabetic and in the control group. With body mass index and the 2-h glucose concentration included in a regression model, 68% of the variation in the number of capillaries per muscle fiber was explained (P < 0.05), with the 2-h insulin value independently accounting for 33%. These findings may suggest that the increased circulating insulin concentrations in IGT subjects have a capillary proliferative effect, perhaps to compensate for reduced capillary insulin diffusion and metabolic capacity of the muscle. PMID- 8194668 TI - Hypoglycemia-induced autonomic failure in IDDM is specific for stimulus of hypoglycemia and is not attributable to prior autonomic activation. AB - We hypothesized, first, that recent antecedent hypoglycemia causes reduced autonomic responses to subsequent hypoglycemia in patients with well-controlled insulin-dependent diabetes mellitus (IDDM) and that the reduced responses are specific for the stimulus of hypoglycemia while the responses to other stimuli are unaltered and, second, that reduced autonomic responses, specifically sympathochromaffin, so-induced are not simply the result of prior activation of the system. To test the first hypothesis, eight patients with IDDM, selected for HbA1c levels < 8.0% and the absence of classic diabetic autonomic neuropathy, were studied twice. On one occasion, clamped hypoglycemia (approximately 2.8 mM) was produced at 1400-1600 on days 2 and 3; on the other occasion clamped euglycemia (approximately 5.6 mM) was produced at those times. On both occasions, autonomic responses to hypoglycemia (approximately 2.8 mM) were determined the morning of day 3 and those to standing, exercise, and a formula meal the morning of day 4. Following afternoon hypoglycemia, 1) the adrenomedullary epinephrine (EPI) response to hypoglycemia was reduced (P = 0.0397) but that to standing, exercise, and a meal were unaltered; 2) the sympathetic neural norepinephrine (NE) response to standing and to exercise was unaltered; and 3) the partially parasympathetic neural-mediated pancreatic polypeptide response to a meal was unaltered. To test the second hypothesis, seven nondiabetic subjects were studied twice, once with cycle exercise (60% peak VO2 x 60 min) and once without exercise 90 min before clamped hypoglycemia (approximately 2.8 mM). Prior exercise had no effect on the EPI, NE, or pancreatic polypeptide responses to hypoglycemia. We conclude, first, that the phenomenon of hypoglycemia-associated autonomic failure can be induced in patients with well-controlled IDDM and is specific for the stimulus of hypoglycemia and, second, that this is not simply the result of prior activation of the system. PMID- 8194669 TI - Reversibility of diabetes- and diuresis-induced alterations in rat bladder dome muscarinic receptors. AB - Previous studies from our laboratory demonstrated that 8 weeks of streptozocin (STZ)-induced diabetes and sucrose-fed diuresis resulted in increases in the density of muscarinic receptors in rat bladder dome and that early insulin treatment (started 3 days after the onset of diabetes) prevented the diabetes induced upregulation (J Pharmacol Exp Ther 248:81-88, 1989; Diabetes 40: 1150 1156, 1991; J Urol 147:760-763, 1992). To determine whether diabetes- and diuresis-induced alterations in muscarinic receptors in rat bladder dome are reversible, we administered insulin (beginning 8 weeks after the onset of diabetes) or removed sucrose from drinking water of diuretic rats (beginning 8 weeks after the onset of diuresis). Five groups of rats were maintained for 16 weeks: 1) STZ-induced diabetic rats (65 mg/kg intravenously); 2) insulin-treated diabetic rats (5-8 U/day insulin subcutaneously beginning 8 weeks after the onset of diabetes); 3) sucrose-fed diuretic rats (5% sucrose in drinking water throughout 16 weeks); 4) sucrose-removed rats (sucrose withdrawn from drinking water after 8 weeks of the sucrose-induced diuretic state); and 5) age-matched control rats. Radioligand receptor binding experiments with [3H]quinuclidinyl benzilate showed an increase in the density of muscarinic receptors in bladder dome of diabetic and sucrose-fed rats compared with age-matched control rats. Removing the 5% sucrose from the drinking water of diuretic rats reversed the increased water intake and urine output, decreased the bladder hypertrophy that accompanied the diuretic state, and corrected the upregulation of the muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194670 TI - Pulsatile insulin secretion from isolated human pancreatic islets. AB - Insulin secretion from the pancreas is pulsatile. The precise site and function of the pacemaker that regulates insulin periodicity in humans have not been determined. We isolated human pancreatic islets from five cadaver organ donors by collagenase digestion and density gradient purification. After 24 h of culture in CMRL-1066 medium at 37 degrees C, aliquots of 200 islets were perifused (1 ml/min for 120 min) with glucose and other secretagogues in oxygenated Krebs-Ringer bicarbonate solution at 37 degrees C. Samples for insulin measurement were taken every minute, and insulin secretion was analyzed by the Clifton and Steiner cycle detection technique. With 3.3 mM glucose (n = 17), insulin oscillations were demonstrated with a periodicity of 9.8 +/- 0.1 min (means +/- SE), mean amplitude was 16.8 +/- 1.8 pM, and overall mean insulin release was 43.8 +/- 4.2 pM. With 16.7 mM glucose (n = 14), no change of insulin periodicity was observed (10.2 +/- 0.9 min), mean amplitude was 41.4 +/- 10.2 pM (P < 0.01 vs. 3.3 mM glucose), and mean insulin release was 118.2 +/- 19.2 pM (P < 0.01 vs. 3.3 mM glucose). Both at 3.3 and 16.7 mM glucose, the addition of 1.4 mM glucagon (n = 4), 15 mM arginine (n = 4), or 100 micrograms/ml tolbutamide (n = 4) caused no change of insulin periodicity but enhanced mean amplitude and mean insulin release compared with glucose alone. These results show that a pacemaker is located within the islets that regulates pulsatile insulin secretion in humans; the pacemaker is remarkably stable, because its periodicity is not affected by factors altering insulin secretion. PMID- 8194671 TI - Risk factors for cardiovascular disease in IDDM. A study of identical twins. AB - Patients with insulin-dependent diabetes mellitus (IDDM) have an excess mortality, predominantly attributable to cardiovascular disease. To determine the effect of IDDM on potential risk factors for cardiovascular mortality, we studied subjects from the British Diabetic Twin Study Group. Forty-five identical twin pairs discordant for IDDM were recruited in addition to 45 matched nondiabetic singleton control subjects. All were selected to be normotensive and to have normal albumin excretion rates. Four variables differed significantly between the diabetic twins and their nondiabetic identical co-twins: diabetic twins had higher systolic blood pressure (sBP) ([mean +/- SD] 127 +/- 17 vs. 123 +/- 18 mmHg, P < 0.05), high-density lipoprotein (HDL) cholesterol (1.36 +/- 0.31 vs. 1.25 +/- 0.29 mM, P < 0.05) and fibrinogen (3.23 +/- 0.81 vs. 2.98 +/- 0.71 mg/ml, P < 0.05) but lower factor VII (114 +/- 34 vs. 122 +/- 31%, P < 0.05). All four of these risk factors were significantly correlated (P < 0.001) within the identical twin pairs, as were the other risk factors. These significant correlations within twins for the risk factors studied reflects the impact of shared genetic and environmental influences. IDDM affects sBP, HDL cholesterol, fibrinogen, and factor VII, but only sBP and fibrinogen are affected adversely. PMID- 8194672 TI - Lilly Lecture 1993. Glycation and diabetic complications. PMID- 8194673 TI - Band importance functions for audiological applications. AB - Recently, band importance functions have been developed for a number of speech tests used in audiology. These functions, as well as the importance functions for average (everyday) speech, are also being considered for the inclusion in the revised Articulation Index standard (submitted for vote to the Acoustical Society of America). In this paper, the band importance functions for different speech materials (usually reported in literature for 1/3 octave bands) have been recalculated to correspond to frequency bands normally used in audiological applications. In addition, criteria for selecting appropriate importance functions and transfer functions are discussed. PMID- 8194674 TI - A model to evaluate and maximize hearing aid performance by integrating the articulation index across listening conditions. AB - A method for integrating the articulation index (AI) across listening conditions was developed and applied to a preliminary model for evaluating and optimizing prescriptions of hearing aid characteristics. The model takes hearing threshold, masking of noise, self-masking of speech, high level cochlear distortion, and the peak-clipping effects of a hearing aid into account. The integrated AI (IAI) across a range of listening conditions is used as a criterion for evaluating a specific hearing aid response characteristic and calculating an optimal frequency gain characteristic that maximizes the IAI. For a high-frequency hearing loss, the frequency-gain characteristics and IAI's derived from an optimal IAI (OIAI), POGO, and NAL prescriptions are compared for two of listening situations: a quiet setting and a setting with a signal-to-noise ratio of -3 dB. The results predict that, in quiet, the OIAI prescription is not significantly different from the well-established prescriptive procedures such as the POGO and the NAL. For the noise condition, however, the optimal IAI model is predicted to be better in terms of speech intelligibility. PMID- 8194675 TI - The effects of syllabic compression and frequency shaping on speech intelligibility in hearing impaired people. AB - The effect of syllabic compression on speech intelligibility is rarely positive and in those cases that positive effects have been found, the same positive results could in general be obtained by frequency shaping of the frequency response curve. We programmed a syllabic compressor on a digital processor; the compressor differed from a conventional syllabic compressor by incorporating a delay in the signal path to suppress overshoots and thus minimize transient distortion. Furthermore, the time constants were short: attack time of 5 msec and release time of 15 msec. The compressor was only active in the high-frequency band. An essentially linear signal was added to deliver the low-frequency speech components. The processing resulted in a frequency response that mirrored the hearing loss near threshold and became much flatter for higher level input signals. Speech intelligibility scores for nonsense consonant-vowel-consonant words embedded in carrier phrases were determined for hearing-impaired persons with sloping audiograms and discrimination losses for speech. Results showed little additional effect of frequency shaping to the existing improved speech score for compressed speech. Optimum results were found for a compression ratio 2 with lower speech scores for linear amplification and for compression ratio 8. We next determined the effect of providing high-frequency emphasis to the speech signal and/or to the compression control signal to compensate for the upward spread of masking. The frequency response at the root-mean-square level was adjusted according to the half-gain rule. The positive effects of moderate compression could be found again; the high-frequency emphasis, however, was positive for the vowels but made consonant recognition poorer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194676 TI - Noise, amplification, and compression: considerations of three main issues in hearing aid design. AB - This paper deals with the following three topics: (1) interfering noise (voice babble, single competing speaker) as the main problem of many hearing-impaired listeners, (2) the amplitude-frequency response of the hearing aid, and (3) the benefit of frequency-dependent compression. Research by the author and his coworkers has shown that: (1) persons with impaired hearing typically need 3 to 6 dB higher speech-to-noise ratios than do normal-hearing listeners--a technically very difficult problem to solve; (2) within a relatively ample range, the speech reception threshold in noise is independent of the amplitude-frequency response; and (3) the small time constants of syllabic compression deteriorate the speech signal. Multichannel amplification (2-4 channels) with automatic gain control for each channel is recommended, optimally adjusted to keep the (variable) speech signal within the impaired ear's limited dynamic range as well as to preserve the intensity differences of successive speech phonemes. PMID- 8194677 TI - Prediction of hearing aid benefit: the role of preferred listening levels. AB - The listening level chosen by a hearing aid wearer for receiving amplified speech in noise has a substantial impact on the benefit that the hearing aid can provide. Chosen listening levels determine (1) the extent to which audibility of speech cues is improved by amplification, (2) the in situ distortion generated by the hearing aid, and sometimes (3) the auditory resolution abilities available to the hearing-impaired listener. All of these variables have been shown to affect hearing aid benefit. Thus, to predict benefit in any particular listening environment, the listening level that the wearer would choose in that setting must be known with some precision. This paper reports two studies of chosen, or preferred, listening levels. We present evidence to show that preferred listening levels vary with changes in the listening environment, especially when the signal to-noise ratio is favorable. We describe a method for predicting preferred listening level changes in some environments that differ in talker levels and/or signal-to-noise ratios. PMID- 8194678 TI - Components and determinants of hearing aid benefit. AB - This study investigates the measured and perceived disabilities and handicaps and associated auditory performance in 309 first-time hearing aid candidates. The results suggest that both disability and hearing aid benefit may be divided into separate components having particular and separate relationships to predictor variables in terms of both auditory and nonauditory characteristics. This division leads to a better understanding of the problems associated with a hearing impairment and their alleviation (or lack of) by provision of a hearing aid. In addition, the results support the development of more appropriate speech identification measures and suggest a potentially important role for measures of the temporal properties of the impaired auditory system. PMID- 8194679 TI - Aided listener preferences in laboratory versus real-world environments. AB - A wearable, fully digital, personal processing unit developed for the study of hearing aid fitting and digital signal-processing techniques was utilized in a preliminary study of hearing aid fitting validation. In a modified single subject, multiple-baseline control design, 12 hearing-impaired listeners indicated their preferences for monaurally aided frequency response alternatives during an initial laboratory session, a real-world session, and a final laboratory session. Listeners' preferences, based on listening to connected speech, were stored in each environment by the personal processing unit. Within blocks of 3 each, subjects were time-lagged with respect to the number of trials to criterion. Subjects participated in 1 of 4 listening conditions, classified according to laboratory stimulus materials; speech recorded in an audiometric sound room in quiet or noise, and speech recorded in a reverberant room in quiet or noise. When compared with preferences obtained in the initial laboratory session, preferences obtained during the final laboratory session agreed better with those obtained in the real world. Overall, however, preferences under laboratory conditions were only fair predictors of preferences under everyday conditions. Results reveal the potential of harnessing the programming and storage capabilities of digital signal-processing technology in implementing new hearing aid fitting strategies. PMID- 8194680 TI - A screening procedure for modified simplex in frequency-gain response selection. AB - The preference for hearing aid frequency-gain responses selected using the modified simplex procedure over that prescribed by NAL-R is not universal. A screening protocol used before individualized fitting may help streamline its use and ensure effective use of clinical time. In this protocol, listeners compare the prescribed frequency-gain response with selected alternate frequency-gain responses. Evaluation with the modified simplex procedure is indicated only when listeners consistently prefer the alternate frequency-gain responses in the screening procedure. Ten hearing aid wearers completed the screening protocol and the full modified simplex procedure. In addition, subjects compared their satisfaction for the prescribed and individually selected frequency-gain responses. The results were examined for efficiency, reliability, sensitivity, and efficacy of the selected frequency-gain response. Findings revealed that the screening protocol allowed reliable identification of listeners who needed fine tuning of the prescribed frequency-gain response. Furthermore, satisfaction for selected frequency-gain response over prescribed frequency-gain response increased as more differences between the two responses were noted. PMID- 8194681 TI - Low-frequency sensorineural loss: clinical evaluation and implications for hearing aid fitting. AB - Spread of excitation in the cochlea places fundamental limits on the interpretation of audiometric pure-tone hearing loss as a simple map of dysfunction along the cochlear partition, and histologic evidence from human temporal bones will be presented to demonstrate the insensitivity of the audiogram to variations in pathology in the case of low-frequency hearing loss. This article will describe a clinical procedure using simultaneous pure-tone masking to improve upon the localization of cochlear disease, particularly for low-frequency hearing losses, and a model for using the Articulation Index (AI) to develop prognoses for hearing aid performance in these cases, which can then be tested. Fourteen patients with low-frequency hearing loss were divided into two groups based upon threshold shifts caused by a pure-tone masker: those that showed normal low-frequency threshold shifts and those that showed marked shifts at frequencies below the masker, indicating greater loss of function than shown by the unmasked audiogram. Hypothetical audiograms were then generated to model a complete loss of apical function for all patients. Measured speech recognition scores were then compared to AI predictions for the actual and hypothetical audiograms. Best agreement for the patients showing normal masking shifts was between the measured scores and the AI for the actual audiogram, whereas the best agreement for the patients showing marked shifts was with the AI for the hypothetical audiogram. The implications for hearing aid recommendation and fitting in these cases are discussed. PMID- 8194682 TI - Noise reduction with FM systems in FM/EM mode. AB - Commercially available noise reduction hearing aids have failed to deliver improved speech recognition in noise over properly fit conventional devices under typical listening conditions (Fabry & Van Tasell, 1990; Gabrielsson, Schenkman, & Hagerman, 1988; Tyler & Kuk, 1989; Van Tasell, Larsen, & Fabry, 1988). The primary factor related to this finding is that speech and noise are mixed at the input of a single microphone; spectral changes are applied equally to both speech and noise, and the signal-to-noise ratio remains unchanged from unprocessed conditions. The purpose of this study was to evaluate a prototype frequency modulated (FM) auditory trainer that allowed use of a remote FM microphone and/or an ear level environmental microphone (EM). For each of five subjects with moderate to severe sensorineural hearing loss, the frequency response of the EM was configured either to match that of the FM response, or to provide a high-pass filter characteristic similar to a noise reduction hearing aid. Speech recognition threshold (SRT) testing noise was measured for five test conditions: 1) FM only; 2) EM only with high-pass filter response (EM-HP); 3) EM only with "standard" response (EM-S) matched to FM; 4) FM/EM-HP combined mode; and 5) FM/EM S mode. Results averaged across subjects indicated that SRTs for the FM only condition were 9 to 10 dB better than those for either EM only condition; data from the combined FM/EM-HP mode averaged 4 dB better than for FM/EM-S conditions. PMID- 8194683 TI - Audiologic results for the bone-anchored hearing aid HC220. AB - Twenty-six patients with severe mixed hearing loss (PTA range 57 to 108 dB HL) were fitted with the "super-bass" bone-anchored hearing aid (BAHA) HC220 and divided into two groups. Group I contained 19 patients who previously used a conventional bone conduction hearing aid that had resulted in serious complaints. Group II contained 7 patients who had previously used an air conduction hearing aid that could no longer be used because of recurrent otorrhoea. Sound field speech audiometry for the patients in Group I revealed that for 7 patients the maximum phoneme score did not change, but that it improved for 12 patients with the HC220, compared with their conventional bone conduction hearing aid. In Group II, the maximum phoneme score improved for 3 patients, worsened for 3 patients and did not change for 1 patient with the HC220, compared with their air conduction hearing aid. Speech recognition in noise was difficult for most of the patients regardless of group. However, results were obtained from 10 patients, and 7 improved significantly with the HC220 compared with their previous aid. Overall, speech recognition with the HC220 was comparable with or better than a conventional bone conduction hearing aid; however, compared with an air conduction hearing aid the results were ambiguous. PMID- 8194684 TI - A new technique for quantifying temporal envelope contrasts. AB - A new technique has been developed for precisely quantifying the temporal contrasts that exist between two sound samples. This technique is based on envelope subtraction, and generates an Envelope Difference Index that may be used to help clarify whether alteration of the natural speech envelope via amplification improves or degrades speech intelligibility. The Envelope Difference Index method may also be used to assess hearing aid saturation, and may have other applications as well. The technique is applicable whenever a precise quantification of the difference between two temporal envelopes is required, regardless of stimulus duration. PMID- 8194685 TI - Natural gastric infection with Helicobacter pylori in monkeys: a model for spiral bacteria infection in humans. AB - BACKGROUND/AIMS: There is no generally accepted model for Helicobacter pylori infection in humans. The aim of this study was to examine the natural history and effect of treatment in rhesus monkeys and sequentially define the immune response to H. pylori in relation to treatment. METHODS: Infection and gastritis were graded blindly by histological analysis and culture of biopsy specimens harvested during gastroduodenoscopies in 26 anesthetized colony-bred monkeys. Plasma H. pylori-specific immunoglobulin (Ig) G levels were determined by enzyme-linked immunosorbent assay. RESULTS: H. pylori and Gastrospirilum hominis-like organisms were present in 13 and 9 monkeys, respectively; 3 animals harbored both organisms, whereas 4 monkeys were not infected. Gastritis score was < or = 1.5 in animals uninfected or infected only with G. hominis-like organisms and > or = 2.0 in all H. pylori-infected animals. IgG ratios were > or = 0.5 in 12 of 13 H. pylori-infected animals and in 2 of 13 H. pylori-negative animals (P < 0.001). One monkey became infected with H. pylori during the observation period, with concurrent increase of gastritis and plasma IgG levels. In untreated animals, infection, gastritis, and plasma IgG levels remained unchanged over 7-15 months. Triple therapy eradicated H. pylori at 6 months in 4 of 6 animals while suppressing gastritis and plasma IgG levels. CONCLUSIONS: Rhesus monkeys harboring H. pylori are persistently infected and have gastritis and elevated specific IgG levels, all of which may respond to appropriate therapy, whereas G. hominis infection is associated with little inflammation. PMID- 8194686 TI - Glutamine stimulates prostaglandin-sensitive Na(+)-H+ exchange in experimental porcine cryptosporidiosis. AB - BACKGROUND/AIMS: Recent studies of piglet cryptosporidiosis showed an injury induced impairment of sodium-glucose cotransport and a prostaglandin-mediated inhibition of neutral NaCl absorption. Because glutamine has been shown to stimulate both neutral and electrogenic Na+ absorption, this study examined the mechanism of prostaglandin-mediated inhibition of NaCl absorption and the effect of glutamine on these processes. METHODS: Ileal mucosa from control and infected pigs was mounted in Ussing chambers for flux studies or incubated with [14C]glutamine or [14C]-glucose for metabolism studies. RESULTS: Glucose and glutamine induced equivalent increases, 2-2.5 microEq.cm-2.h-1, in Na+ absorption and short-circuit current in control ileum. Despite a reduction in villous surface area to one third of the control, glutamine enhanced both neutral and electrogenic Na+ absorption in the infected ileum by 3.5 +/- 0.5 microEq.cm-2.h 1, whereas glucose was only half as effective (P < 0.05). In addition, glutamine was oxidized to CO2 at rates three times those of glucose. Indomethacin enhanced, whereas amiloride, prostaglandin E2, and Cl-free solutions inhibited the glutamine-induced neutral Na+ transport. CONCLUSIONS: Glutamine-stimulated neutral Na+ absorption is mediated by a prostaglandin-sensitive apical Na(+)-H+ exchange mechanism. The heightened Na(+)-H+ exchange and tissue oxidation of glutamine suggest that glutamine is superior to glucose for use in oral rehydration solutions. PMID- 8194687 TI - A placebo-controlled trial of cyclosporine enemas for mildly to moderately active left-sided ulcerative colitis. AB - BACKGROUND/AIMS: Uncontrolled studies suggest that cyclosporine administered as an enema may be of benefit for left-sided ulcerative colitis and safer than intravenous or oral administration. The efficacy and safety of cyclosporine enemas for left-sided ulcerative colitis in a placebo-controlled trial was assessed. METHODS: Steroid and mesalamine enemas were withdrawn before the study. Forty patients were assigned to 1 of 4 strata: no concomitant therapy, oral steroids, oral salicylates, or oral steroids and salicylates. After stratification, patients were randomized to nightly treatment with 350 mg cyclosporine (n = 20) or placebo (n = 20) enemas. Clinical response was determined at baseline and 4 weeks by endoscopy, physician assessment, and a patient diary of daily symptoms. Trough blood cyclosporine levels were measured by high-performance liquid chromatography. RESULTS: At 4 weeks, 8 of 20 patients (40%) who received cyclosporine showed clinical improvement compared with 9 of 20 patients (45%) who received placebo. One patient receiving cyclosporine had reversible neutropenia attributable to sulfasalazine, and another patient receiving cyclosporine was unable to tolerate the enema vehicle. No other toxicity was noted during the trial. Blood cyclosporine levels were detectable in only two patients. CONCLUSIONS: Cyclosporine enemas administered in a dosage of 350 mg/day for 4 weeks are not efficacious in mildly to moderately active left sided ulcerative colitis. PMID- 8194688 TI - Superficial-type adenomas and adenocarcinomas of the colon and rectum: a comparative morphological study. AB - BACKGROUND/AIMS: It has been uncertain whether colorectal carcinomas preferentially arise on preexisting adenomas or de novo. However, from a morphological viewpoint, it seems unlikely that pedunculated or exophytic malignant polyps progress to the deeply ulcerated advanced carcinomas usually found clinically. METHODS: The morphological features of 26 nonpolypoid, superficial-type colorectal tumors (17 adenomas and 9 adenocarcinomas) were compared to clarify the developmental route of colorectal carcinomas. RESULTS: The adenomas and adenocarcinomas were very similar in size and gross appearance; however, examination of the surface appearances of unsectioned tumors by dissecting microscopy was helpful for distinguishing the two. Histologically, no adenomatous tissue was found in any case of superficial-type adenocarcinoma. Five of the nine adenocarcinomas, even including those of small size, invaded the submucosal layer, and two showed lymph node metastasis. CONCLUSIONS: These findings suggest that superficial-type adenocarcinomas show rapid growth and aggressive behavior. We suggest that this type of carcinoma may not progress by the adenoma-to-carcinoma pathway but that it may arise from a very small superficial-type adenoma. PMID- 8194689 TI - Satiety effects of cholecystokinin in humans. AB - BACKGROUND/AIMS: Cholecystokinin (CCK) inhibits gastric emptying and may exert satiety effects in several species, including humans. Because the effects of physiological doses of CCK on satiety in humans is unclear, the satiety effects of CCK-33 in physiological levels in lean and obese subjects were studied. METHODS: CCK-33 was infused intravenously to 32 healthy men or women (14 obese, all women; 18 lean, 4 men and 14 women) in doses that elicited plasma CCK concentrations in the physiological range. The effects of these infusions on feelings of hunger, wish to eat, fullness, and prospective feeding intentions were measured on visual analogue scales and compared with saline during a 1-hour infusion period. RESULTS: The CCK infusions induced significant decreases in hunger feelings, wish to eat, and prospective feeding intentions (P < 0.05), whereas fullness tended to be increased (P = 0.054). No clear differences between lean and obese subjects were observed apart from a more marked decrease in fullness and increase in prospective feeding intentions during the 1-hour saline infusion in the lean group (P < 0.05). CONCLUSIONS: CCK infusion leading to physiological plasma levels significantly increases satiety in humans. PMID- 8194690 TI - Tumor necrosis factor alpha-producing cells in the intestinal mucosa of children with inflammatory bowel disease. AB - BACKGROUND/AIMS: Cytokines are thought to be important in mediating tissue damage in inflammatory bowel disease (IBD). Many of the in vivo activities of tumor necrosis factor alpha (TNF-alpha) match the changes found in IBD, but its importance is controversial. METHODS: A sensitive, reverse hemolytic plaque assay was used to determine the frequency of TNF-alpha secreting cells isolated from mucosal biopsy specimens of children with Crohn's disease or ulcerative colitis (UC) and non-IBD controls before and after medical treatment. RESULTS: Frequency of TNF-alpha secreting cells was significantly increased in biopsy specimens from children with mild, nonspecific inflammation compared with those with histologically normal intestine. Frequency did not increase in UC compared with children with nonspecific inflammation but was significantly greater in Crohn's disease than in UC. After treatment, the frequency of TNF-alpha secreting cells was reduced in patients receiving cyclosporin A, not reduced in patients with steroids or enteral nutrition, and not changed with treatment in UC. CONCLUSIONS: TNF-alpha secreting cells are increased in the mucosa of inflamed intestine, regardless of pathogenesis. In patients with IBD, higher levels are seen in Crohn's disease than in UC, probably reflecting the extensive T-cell activation in Crohn's disease. No relation existed between histological healing and the frequency of TNF-alpha-secreting cells. PMID- 8194692 TI - The effects of psychological stress on the esophagogastric junction pressure and swallow-induced relaxation. AB - BACKGROUND/AIMS: Short-term psychological stress increases pressure in the upper esophageal sphincter and increases esophageal contraction amplitude. The effects of short-term psychological stress on the two sphincteric mechanisms at the esophagogastric junction (EGJ), the lower esophageal sphincter (LES) and crural diaphragm, were studied. METHODS: Studies were performed in 20 normal, healthy subjects. LES and crural diaphragm functions were measured simultaneously using an electrode sleeve sensor. Three psychological stress tasks, math, cold, and stress interview, were tested. The data were analyzed for tonic (end expiratory) and phasic (inspiratory increase) EGJ pressure and electromyographic changes during the stress period. Spontaneous swallow-induced EGJ relaxation was also assessed. RESULTS: A significant decrease in tonic EGJ pressure occurred during the math and cold tasks. The tonic EGJ pressure was 19 +/- 2 and 14 +/- 2 during baseline and the math task, respectively. Stress caused no change in the phasic EGJ pressures. Tonic and phasic crural diaphragm electromyographic activity increased during all three stress periods. Spontaneous swallow-induced relaxation at the EGJ during the stress periods was reduced from 60% +/- 2% in the baseline to 39% +/- 5% during the stress periods. CONCLUSIONS: Short-term psychological stress lowers EGJ pressure through inhibition of the LES and increases tonic and phasic crural diaphragmatic contraction. Diminished swallow-induced relaxation at the EGJ during stress may lead to changes in esophageal contractions. PMID- 8194691 TI - Vasoactive intestinal polypeptide gene expression is characteristically higher in opossum gastrointestinal sphincters. AB - BACKGROUND/AIMS: Vasoactive intestinal polypeptide (VIP) has been suggested to be an inhibitory neurotransmitter in the sphincteric and nonsphincteric smooth muscles of the gut. However, the relative gene expression of VIP in these functionally diverse regions is not known. METHODS: The gastrointestinal smooth muscle sphincters of opossums were excised from the adjoining nonsphincteric smooth muscles. RNAs were isolated and subjected to blot hybridizations with VIP complementary DNA probe. Relative expression of VIP gene was quantitated using the densitometric scanning of the VIP messenger RNA (mRNA) transcripts. The cellular specificity of VIP gene expression was investigated in cultures of neuroblastoma cells and myenteric plexuses and compared with those of the smooth muscle cells. RESULTS: The data showed higher levels of VIP mRNA in the sphincteric than the adjoining nonsphincteric tissues. VIP mRNA were found in significantly higher amounts in the myenteric neurons and neuroblastoma cells than in the smooth muscle cells. CONCLUSIONS: VIP gene expression was significantly higher in the sphincteric smooth muscle regions than in the nonsphincteric regions of the gut. The studies provide further evidence for the role of VIP in neurotransmission of the gut. PMID- 8194693 TI - P2 purinergic receptor regulation of mucus glycoprotein secretion by rabbit gastric mucous cells in a primary culture. AB - BACKGROUND/AIMS: Physiological regulation of gastric mucus secretion has not been well studied. The present study investigated the effects of adenosine 5' triphosphate (ATP), a P2 purinergic receptor agonist, and its analogues on gastric mucus secretion using gastric mucous cells in a primary culture. METHODS: A monolayer culture of gastric mucous cells from adult rabbits were prepared after enzyme digestion. Mucus secretion was estimated from the release of [3H]glucosamine from prelabeled cells. Intracellular calcium concentration ([Ca2+]i) was monitored by a Ca(2+)-sensitive probe, indo-1. Prostaglandin E2 (PGE2) in the media was measured by an enzyme-linked immunoassay. RESULTS: ATP significantly stimulated mucus secretion by these cells at nontoxic doses in a dose-dependent fashion. The order of potency of ATP analogues stimulating mucus secretion was alpha beta-methylene ATP > ATP > 2-methylthio ATP, whereas adenosine, a P1 purinergic receptor agonist, had no effect. ATP also induced an elevation of [Ca2+]i in a dose-dependent fashion. The efficacy of ATP analogues to increase [Ca2+]i showed a similar potency to their actions on mucus secretion. ATP increased PGE2 at relatively higher concentrations, whereas indomethacin did not block ATP-induced increase of mucus secretion. CONCLUSIONS: These results suggest that ATP stimulates mucus secretion by gastric mucous cells through P2 purinergic receptors; this appears to be mediated by intracellular calcium not by endogenous PGE2. PMID- 8194694 TI - Interleukin 1 induces a neurally mediated colonic secretion in rats: involvement of mast cells and prostaglandins. AB - BACKGROUND/AIMS: Interleukin 1 beta (IL-1 beta) is known to regulate intestinal ion and water transport in vitro through prostaglandin release. This study investigated the effect of IL-1 beta on colonic net water flux in vivo to determine its nature (nerve mediation versus action on the epithelium), the mediators involved, and its relationship with mast cell degranulation. METHODS: Isolated colonic loops of anesthetized animals were infused with Ringer's buffer containing [14C]polyethylene glycol 4000. Net water flux was calculated according to 14C activity determined in the effluent collected at 15-minute intervals. Histological analysis was used to identify intact mast cells in colonic sections and radioimmunoassay to determine histamine levels. RESULTS: Both IL-1 beta and the calcium ionophore A23187 induced colonic hypersecretion during 30 minutes. This effect was blocked by tetrodotoxin, doxantrazole, and indomethacin but not chlorpheniramine. Recombinant human interleukin 1 beta decreased the number of intact mast cells. This effect was eliminated by doxantrazole but not tetrodotoxin or indomethacin. A23187 or IL-1 beta increased histamine levels in the effluent during 75 and 45 minutes, respectively. CONCLUSIONS: In vivo, rhL-1 beta induces colonic hypersecretion in rats. This effect is nerve mediated but not H1 receptor mediated and involves mast cell degranulation and prostaglandin release. PMID- 8194695 TI - Do characteristics of adenomas on flexible sigmoidoscopy predict advanced lesions on baseline colonoscopy? AB - BACKGROUND/AIMS: Colonoscopy is presently recommended for patients with any benign neoplasm found on sigmoidoscopy. The purpose of this study was to determine whether characteristics of adenomas on flexible sigmoidoscopy predict advanced lesions on baseline colonoscopy. METHODS: A total of 226 asymptomatic and symptomatic patients with adenomas noted on flexible sigmoidoscopy at a large, multispecialty medical group were prospectively studied. The histology, size, and number of benign polyps on flexible sigmoidoscopy were compared with those on subsequent colonoscopy. Advanced lesions were defined as adenomas > 1 cm in diameter or with villous or severe dysplasia histology. Univariate comparisons were assessed using the chi 2 test and multivariate analysis with stepwise logistic regression. RESULTS: There was a 24% prevalence of new adenomas found on colonoscopy. Six percent of the patients had advanced lesions on colonoscopy, and none had cancer. Multivariate analysis indicated that findings on flexible sigmoidoscopy predict (P < 0.01) those on colonoscopy. Patients with advanced lesions on sigmoidoscopy had a > 10% prevalence of an advanced lesion on colonoscopy. Patients with small (< or = 1 cm) tubular adenoma(s) on sigmoidoscopy had a < 1% occurrence of an advanced synchronous lesion. CONCLUSIONS: The histology and size of benign neoplasms found on flexible sigmoidoscopy predict findings on baseline colonoscopy. PMID- 8194696 TI - Rat gastric motor response to food protein-induced anaphylaxis. AB - BACKGROUND/AIMS: Antigen challenge of sensitized rats leads to delayed gastric emptying, but the mechanism (gastroparesis or prolonged trituration) and mediators are unknown. METHODS: Hooded Lister rats were sensitized by intraperitoneal injection of egg albumin as antigen, and control rats were sham sensitized. On day 14, antral manometric and antroduodenal myoelectric activities in sensitized and sham-sensitized rats were recorded in response to antigen challenge, and the contractility of gastric antral circular muscle strips (mucosa intact) in standard tissue baths was measured in response to antigen or other agents. RESULTS: In vivo, the intragastric antigen challenge of sensitized (but not sham-sensitized) rats provoked diarrhea, reduction in the antral motility index, and disruption of the duodenal migrating motor complex. In vitro, antigen induced a tonic contraction of antral circular muscle segments from sensitized animals. Doxantrazole, but not disodium cromoglycate, inhibited antigen-induced contraction. Whereas histamine, 5-hydroxytryptamine, prostaglandins, leukotrienes, and platelet-activating factor contracted gastric muscle strips, neither specific antagonists, prostaglandin synthase, or 5-lipoxygenase inhibitors inhibited antigen-induced contraction. Tetrodotoxin increased antigen induced contraction; however, the antigen-induced contraction was unaffected by atropine, guanethidine, or NG-nitro-L-arginine methyl ester. CONCLUSIONS: Food protein-induced, immunoglobulin E-mediated delayed gastric emptying in sensitized rats is associated with a transient reduction in gastric antral contractions. Antigen-induced contraction appears to be under nonadrenergic, noncholinergic, nonnitroxinergic inhibitory neural control. PMID- 8194697 TI - Mononuclear cells from infants allergic to cow's milk secrete tumor necrosis factor alpha, altering intestinal function. AB - BACKGROUND/AIMS: Intestinal dysfunction observed during cow's milk allergy (CMA) is incompletely understood, and neither the effector cells nor the mediators responsible have been clearly identified. This study was undertaken to better characterize the implication of mononuclear cells in food allergy. METHODS: Peripheral blood mononuclear cells (PBMC) from infants with CMA were cultured in the presence of cow's milk proteins (CMP), and the release of tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin 4 and 6 was measured. The effect of culture supernatants was tested on HT29 cl.19A intestinal cell monolayers mounted in Ussing chambers. RESULTS: When stimulated by CMP, PBMC from infants with CMA released more TNF-alpha than those from control infants (429 +/- 92 vs. 205 +/- 34 pg/mL). Culture supernatants did not directly stimulate electrogenic chloride secretion by HT29 cl.19A cells, but epithelial barrier capacity was altered as shown by the significant decrease in electrical resistance (85 +/- 17 vs. 135 +/- 14 omega.cm2 in controls) and the increases in intact horseradish peroxidase, [14C]mannitol, and 22Na+ fluxes. These effects were reversed when culture supernatants were neutralized with anti TNF-alpha antibodies. Recombinant human-TNF-alpha altered the HT29 cl.19A epithelial barrier capacity, and its effect was highly potentiated by IFN-gamma. CONCLUSIONS: These results indicate that during CMA, the high level of TNF-alpha released by mononuclear cells after milk protein challenge acts synergistically with IFN-gamma to increase the intestinal permeability. PMID- 8194698 TI - The role of capsaicin-sensitive sensory neurons in healing of HCl-induced gastric mucosal lesions in rats. AB - BACKGROUND/AIMS: Capsaicin-sensitive sensory neurons are important in protecting the stomach against damage. This study investigated the role of these sensory neurons in the healing of gastric lesions. METHODS: Rats fasted for 18 hours were given 1 mL of 0.6N HCl orally for induction of gastric lesions; they were then fed normally from 1 hour later. On various days after HCl treatment, the area of lesion, acid secretion, mucosal DNA synthesis, mucosal H+ permeability, and blood flow responses were measured. RESULTS: Ablation of sensory neurons by capsaicin pretreatment did not affect the development of gastric lesions in response to HCl but significantly delayed the healing of these lesions. The damaged mucosa secreted less acid and had minimal changes in DNA synthesis but showed a marked increase in H+ permeability, resulting in luminal acid loss accompanied by an increase of mucosal blood flow. Sensory deafferentation did not have any influence on such changes in the damaged stomach, except the mucosal hyperemic response to acid. CONCLUSIONS: Capsaicin-sensitive sensory neurons may contribute to the healing of gastric lesions by mediating the mucosal hyperemic responses associated with acid back-diffusion and by facilitating acid disposal in the mucosa. PMID- 8194699 TI - Inhibition of phase III activity by acidifying stomach in vagally denervated and innervated dogs with gastric pouches. AB - BACKGROUND/AIMS: Intragastric acidification at pH 1.0 strongly inhibits phase III contractions in the dog, but this mechanism is not well known. We studied the mechanism in conscious dogs. METHODS: Vagally denervated and innervated gastric pouch dogs were prepared. Force transducers were chronically implanted on the serosa of the pouch, main stomach, and mid-duodenum. The pH of the perfusate was monitored. RESULTS: Administration of histamine (40 micrograms.kg-1.h-1 intravenously [i.v.]) and instillation of acidic saline at pH 1.0, but not pH 2.0, into the main stomach strongly inhibited the motilin-induced (0.1 microgram/kg i.v.) phase III activity in the main stomach and the innervated pouch but did not influence contractions in the extrinsically denervated pouch. Famotidine completely reversed the histamine-induced inhibition of phase III in the main stomach and Pavlov pouch. Acidification of the pouch itself or duodenum at pH 1.0 did not affect contractions in the main stomach and pouch of either type. CONCLUSIONS: The mechanism of inhibition of motilin-induced phase III activity by acid in the stomach involves the intact vagovagal reflex, but sympathetic participation is not completely ruled out. The inhibition of motilin induced phase III activity may originate in the antral mucosa of the stomach. PMID- 8194700 TI - Phenotypic variability of familial adenomatous polyposis in 11 unrelated families with identical APC gene mutation. AB - BACKGROUND/AIMS: Familial adenomatous polyposis is caused by germline mutation of the adenomatous polyposis coli (APC) gene. Affected individuals develop hundreds of colorectal adenomas at young age and can have extracolonic lesions. METHODS: This study evaluated the phenotype of 74 patients with familial adenomatous polyposis from 11 unrelated families with an identical 5-base pair deletion at codon 1309 of the APC gene. RESULTS: Polyp density in the sigmoid colon of 16 patients from 9 families varied from 3.8 to 13.1/cm2, and mean polyp diameter ranged from 1.4 +/- 0.1 to 2.7 +/- 0.1 mm. The distribution of colonic adenomas also varied, with diffuse polyposis in 6 patients but relative polyp sparing in the more proximal colon in 6 others. Age at diagnosis of colorectal cancer ranged from 19 to 62 years, but the mean age did not differ among the 4 families with multiple cases. Colorectal cancers occurred predominantly in the rectosigmoid (80%) but also in the more proximal colon. The percentage of patients affected by various extracolonic lesions differed widely among and within the 11 families (range, 0%-100%). CONCLUSIONS: APC gene mutation at codon 1309 results in intrafamily and interfamily phenotypic variation in familial adenomatous polyposis. Environmental and/or other genetic factors must play roles in the expression of germline APC gene mutations. PMID- 8194701 TI - In vivo visualization of lymphatic microvessels and lymphocyte migration through rat Peyer's patches. AB - BACKGROUND/AIMS: In the small intestine, lymphocytes migrate through Peyer's patches. The distribution of lymphatic microvessels in rat Peyer's patches and lymphocyte traffic through them were studied. METHODS: Vital dyes were injected via a micropipette into the Peyer's patches tissue to fill lymphatic microvessels and to stain lymphocytes in lymphatic microvessels. RESULTS: Direct microscopic observation revealed a dense plexus of lymphatic microvessels in the perifollicular and interfollicular areas. Injection of the dyes into the germinal center failed to delineate lymphatic microvessels. The lymphatic microvessels in the perifollicular area were filled with lymphocytes. Most lymphocytes in the perifollicular lymphatics stayed in the lymphatic microvessels. Some lymphocytes became detached and drained into lymphatic microvessels in the interfollicular areas. Lymphocytes then moved toward the submucosal lymphatics beneath the villi around the Peyer's patches. The interfollicular lymphatics did not display contractile activity but had valves. Opening and closing of valves was synchronized with the respiration and the back and forth flow of lymphocytes. CONCLUSIONS: There are numerous lymphocytes in a dense lymphatic network in the perifollicular and interfollicular areas of Peyer's patches. This well-developed lymphatic network has the potential capacity for storage of lymphocytes and modulation of lymphocyte migration. PMID- 8194702 TI - Localization of bicarbonate transport along the crypt-villus axis in rabbit ileum. AB - BACKGROUND/AIMS: HCO3- can be absorbed as well as secreted in the rabbit ileum. With 25 mmol/L HCO3- on the serosal side only, a serosa-to-mucosa flux (Jsm) is found; with 25 mmol/L on the mucosal side only, epinephrine elicits a mucosa-to serosa flux (Jms). This study aimed to localize these two processes along the crypt-villus axis. METHODS: Excised ileal segments were exposed luminally to 2 mol/L Na2SO4 (hypertonic treatment) or to isotonic Ringer's solution for 15 minutes. Mucosa was then chamber-mounted, and measurements were made of Jsm or Jms and of short-circuit current (Isc) responses to glucose plus alanine and to either theophylline or epinephrine. RESULTS: With HCO3-/CO2 added to the serosal side only, hypertonically treated tissues showed a 22% decline in Jsm; a 25% decline in Isc response to theophylline; and a 71% decline in Isc response to glucose plus alanine compared with control. With HCO3-/CO2 added to the mucosal side only, tissues showed 92% and 87% declines in Jms and Isc responses to epinephrine, respectively, and a 87% decline in Isc response to glucose plus alanine. Histological examination showed destruction of villus caused by hypertonic treatment but sparing of crypt cells. CONCLUSIONS: Both HCO3- and Cl- are secreted mainly by crypt cells and absorbed mainly by villus cells. PMID- 8194703 TI - Interleukin 1 beta inhibits gastric emptying in rats: mediation through prostaglandin and corticotropin-releasing factor. AB - BACKGROUND/AIMS: Interleukin 1 beta (IL-1 beta) increases the release of corticotropin-releasing factor (CRF) in the brain through prostaglandin pathways. Because central CRF inhibits gastric motor function, the influence and mechanism of action of intracisternal injection of IL-1 beta on gastric emptying were investigated. METHODS: The 20-minute rate of gastric emptying of a nonnutrient test meal was assessed by the phenol red methylcellulose method 30 minutes after injection of human recombinant IL-1 beta in conscious rats. RESULTS: IL-1 beta injected intracisternally (0.01-1 ng) or intravenously (0.01-10 ng) dose dependently decreased gastric emptying by 10%-82% and 0%-89%, respectively. The median effective dose (ED50) was 30-fold lower when IL-1 beta was injected intracisternally (0.1 ng) than intravenously (3 ng). The inhibitory effect of intracisternal IL-1 beta had a rapid onset (within 20 minutes) and was long lasting (6 hours). Indomethacin (5 mg/kg, intraperitoneally) completely prevented the 61% inhibition induced by intracisternal IL-1 beta (0.1 ng) but had no effect on CRF-induced (600 ng) 72% inhibition of gastric emptying. The intracisternal injection of the IL-1 receptor antagonist (100 ng) or the CRF antagonist [DPhe12, [DPhe12,Nle21,38,C alpha MeLeu37]CRF12-41 (20 micrograms) prevented by 100% and 52%, respectively, the inhibition of gastric emptying evoked by intracisternal IL 1 beta (0.1 ng). The antagonists alone had no effect on basal gastric emptying. CONCLUSIONS: IL-1 beta acts in the brain to induce a long-lasting inhibition of gastric emptying; IL-1 beta action is mediated through central IL-1 receptors and prostaglandin- and CRF-dependent mechanisms. PMID- 8194704 TI - Adaptation of enteroendocrine cells in response to jejunal-ileal transposition in the rat. AB - BACKGROUND/AIMS: Enteroendocrine cell subpopulations are uniquely distributed along the crypt-villus and cephalocaudal axes of the small intestine. These regional differences in enteroendocrine cell expression, which are maintained in spite of rapid turnover of the epithelium, serve as descriptive markers of physiological differences along the length of the bowel. This study aimed to determine the influence of luminal contents on the maintenance of regional differentiation patterns of enteroendocrine and enterocytic phenotypes. METHODS: Sections of jejunum and ileum were surgically transposed in rats, leaving the innervation and blood supply to the transposed segments intact. The animals were killed 1, 4, and 8 weeks after surgery. Enteroendocrine cell subpopulations and enterocytic cell markers were studied immunohistochemically. RESULTS: No change in regional expression patterns was seen in response to the altered luminal environment by any of the enterocytic markers and four of the five enteroendocrine cell subpopulation markers. Eight weeks after surgery, the number of gastrin-expressing enteroendocrine cells increased in ileal segments transplanted proximally. CONCLUSIONS: Although luminal signals can affect intestinal stem cells to alter their proliferation rates, the luminal environment has only limited effects on the regional-specific expression of enteroendocrine or enterocytic products. PMID- 8194705 TI - Allelic deletions of MCC/APC and p53 are frequent late events in human gastric carcinogenesis. AB - BACKGROUND/AIMS: Frequent allelic deletion affecting the mutated in colon cancer/adenomatous polyposis coli (MCC/APC) and p53 tumor suppressor gene loci has been reported in human cancers. However, simultaneous correlative analyses of these two abnormalities or their timing in gastric tumorigenesis have not been performed. METHODS: To ascertain the relation between and timing of allelic deletions of MCC/APC and p53 in gastric carcinogenesis, 52 matched sets of normal tissue, gastric carcinoma, and adjacent gastric dysplasia were evaluated. RESULTS: Allelic deletion was seen in 33% of informative cancers at MCC, in 34% at APC, and in 64% at p53. Losses involving MCC correlated exactly with those affecting APC. Limited mutational analysis failed to reveal point mutations in selected exons of MCC. The frequencies of allelic losses at the two loci did not differ significantly among histological types. There was no allelic loss in gastric dysplasia. Interestingly, allelic deletion at MCC/APC was never detected in tumors negative for allelic deletion of p53. CONCLUSIONS: These results suggest that allelic deletions involving p53 and MCC/APC are common late events in gastric cancer. They also imply that allelic deletions affecting MCC/APC may not occur independently of those involving p53 in gastric tumorigenesis. PMID- 8194706 TI - p53 mutations in Barrett's adenocarcinoma and high-grade dysplasia. AB - BACKGROUND/AIMS: Allelic losses of chromosome 17p and overexpression of p53 protein have been reported in Barrett's adenocarcinomas. This study aimed to determine the stage in which p53 mutations arise in neoplastic progression in Barrett's esophagus and their relationship to the clonal evolution of cancer. METHODS: Fourteen patients with high-grade dysplasia, adenocarcinoma, or both arising in Barrett's esophagus were evaluated. Flow cytometric cell sorting was used to obtain purified populations of neoplastic cells for analysis of p53 mutations. DNA was extracted, and exons 5 through 9 of the p53 gene were amplified by polymerase chain reaction. Amplified DNA was sequenced and analyzed by automated sequencing. RESULTS: Nine of the 14 patients had p53 mutations. Six of the 9 patients had regions of high-grade dysplasia that could be evaluated; all 6 had p53 mutations in high-grade dysplasia. In 3 patients, the same p53 mutations were found in both high-grade dysplasia and adenocarcinoma. All 14 patients had aneuploidy. In 4 patients, diploid cell populations could also be evaluated for p53 mutations; 3 of the 4 patients had p53 mutations in diploid cell populations. In 2 patients, the same p53 mutation was found in multiple aneuploid cell populations within a cancer. CONCLUSIONS: p53 mutations occur frequently in Barrett's adenocarcinomas. They develop in diploid cell populations. The same p53 mutations are then found in aneuploid cell populations in high-grade dysplasia, in cancer, and in multiple aneuploid cell populations in cancer. PMID- 8194707 TI - Transmission of hepatitis C in an isolated area in Japan: community-acquired infection. The South Kiso Hepatitis Study Group. AB - BACKGROUND/AIMS: The spread of hepatitis C virus (HCV) infection not due to drug needle sharing or transfusion is largely unknown in communities. A search for risk factors for HCV infection in an endemic area might elucidate inapparent modes of transmission. METHODS: We conducted screening for hepatitis virus markers and parenteral exposures to blood among 435 inhabitants in an isolated area known for its endemicity for non-A, non-B hepatitis and in a nonendemic area with 1542 inhabitants. RESULTS: The prevalence of hepatitis B surface antigen was the same in both areas. The prevalence of antibody to HCV verified by the recombinant immunoblot assay was 32.4% in the highly endemic area and 2.3% in the nonendemic area (P < 0.001). Risk factors for HCV infection in the highly endemic area were complex but included folk remedies such as acupuncture and "vacuuming" for congested blood in muscle by the use of a warm glass bottle. CONCLUSIONS: Folk remedies such as acupuncture and cutting of the skin using nonsterilized knives should be considered as possible routes of HCV transmission not associated with blood transfusion or sharing of drug paraphernalia. PMID- 8194708 TI - Analysis of hepatitis C virus genome in patients with autoimmune hepatitis type 2. AB - BACKGROUND/AIMS: Hepatitis C virus (HCV) RNA is detectable in a proportion of patients with autoimmune hepatitis type 2, which is characterized by liver-kidney microsomal antibodies (LKM). Therefore, the genotype and sequence of HCV were studied in these patients. METHODS: Sera from 43 LKM-positive and anti-HCV positive patients (15 from Germany and 28 from Italy) and 82 LKM-negative and anti-HCV-positive patients (57 from Germany and 25 from Italy) were examined. RESULTS: Genotyping revealed that the rate of genotype III HCV according to Okamoto's classification in patients with LKM antibody-positive autoimmune hepatitis type 2 was higher than in LKM-negative patients (22.0% vs. 2.4%; P < 0.05). This was because of an increase of genotype III in our patients from Italy. No HCV mutations were found that show a closer sequence homology to cytochrome P450IID6, the major LKM-1 antigen. Deletions in the envelope and nonstructural region 5 were found. CONCLUSIONS: Because a specific HCV sequence is not associated with the induction of LKM-1 autoantibodies, future research must focus on host factors and possibly additional environmental factors. PMID- 8194709 TI - Body composition in nonalcoholic cirrhosis: the effect of disease etiology and severity on nutritional compartments. AB - BACKGROUND/AIMS: Previous studies of body composition in cirrhosis have either measured only one body compartment, used alcoholic subjects, or not corrected body composition for physical characteristics. The aim of this study was to perform a detailed analysis of body composition in subjects with nonalcoholic cirrhosis. METHODS: Simultaneous measurements of total body potassium and total body water were performed and values of body cell mass and body fat were corrected for physical characteristics. RESULTS: Child's class C patients had a significantly lower mean total body potassium index (i.e., percent observed value/expected value) and body fat index than class A or B patients. Eighty-one percent of class C patients had simultaneous reductions in body fat and body cell mass, and 71% of patients with class A disease had a significant reduction in either or both compartments. Nine patients showed the pattern of tissue loss seen with short-term starvation. Fourteen patients showed the pattern of tissue loss seen in physiological stress. CONCLUSIONS: Severe liver disease is characterized by significant reductions in body fat and body cell mass, most class A patients have a significant reduction in some nutritional compartments, and the pattern of tissue loss may reflect mechanisms of tissue wasting. PMID- 8194710 TI - Predictive factors for postoperative recurrence of hepatocellular carcinoma. AB - BACKGROUND/AIMS: The survival rate for hepatocellular carcinoma after hepatectomy remains unsatisfactorily low because of the high recurrence rate. The purpose of this study was to elucidate predictive factors for postoperative recurrence of hepatocellular carcinoma. METHODS: Univariate analysis and a multiple regression model were used to retrospectively determine the factors potentially related to recurrence in 98 patients with hepatocellular carcinoma who had undergone curative hepatic resection. RESULTS: DNA diploidy, absence of alcohol abuse, and absence of vascular invasion were determined to be independent favorable predictive factors using a multivariate analysis with Cox's proportional hazards model. A predictive index was developed using these three factors according to the following equation: 1.486 x (O = DNA diploidy or 1 = DNA aneuploidy) + 1.138 x (O = absence or 1 = presence of alcohol abuse) + 0.946 x (O = absence or 1 = presence of vascular invasion). This index was used to classify the patients into two groups with good or poor prognosis. The median time for disease recurrence for the two groups was 24.1 and 9.2 months, respectively (P < 0.001). CONCLUSIONS: The results may be useful in the determination of treatment strategies and postoperative follow-up schedules and in the design and analysis of future clinical trials of therapy for hepatocellular carcinoma. PMID- 8194711 TI - Adenovirus-mediated transfer of human lipase complementary DNA to the gallbladder. AB - BACKGROUND/AIMS: Despite many improvements in current therapy, exocrine pancreatic insufficiency remains a significant problem in cystic fibrosis. To establish a new therapy for exocrine pancreatic insufficiency, the feasibility of transferring the human pancreatic lipase complementary DNA to the gallbladder as a possible target using a recombinant adenovirus vector was evaluated. METHODS: The adenovirus vector AdCMV. Lip was constructed using the cytomegalovirus immediate early promoter to drive the human pancreatic lipase complementary DNA. In vitro infection of the human gallbladder epithelial cell line HS-181 and ex vivo infection of the sheep gallbladder with AdRSV. beta-gal (an adenovirus vector containing the Escherichia coli lacZ [(beta-galactosidase] gene) or AdCMV. Lip were evaluated. RESULTS: The supernatant from AdCMV. Lip-infected HS-181 showed the secretion of active lipase for at least 2 weeks in vitro. The epithelium of gallbladder infected with AdRSV.beta-gal ex vivo showed the expression of the beta-galactosidase. The fluid from the gallbladder lumen infected with AdCMV. Lip showed the increased lipase activity. CONCLUSIONS: These observations show that an adenovirus vector can transfer a human pancreatic enzyme in vitro and ex vivo, suggesting the feasibility of in vivo gene therapy for exocrine pancreatic insufficiency in cystic fibrosis. PMID- 8194712 TI - Frequent alterations of the tumor suppressor genes p53 and DCC in human pancreatic carcinoma. AB - BACKGROUND/AIMS: The pathogenesis of pancreatic cancer is poorly understood. The multigenetic nature of carcinogenesis has been best documented in colon cancer. The relevance of this model was suggested for other epithelial tumors. Only advanced stages of pancreatic cancer are usually detected because of late diagnosis. Analysis of accumulated, diverse genetic changes could allow further understanding of putative mechanisms involved in tumor development. Activated c Ki-ras oncogene has been shown to be a frequent event. However, additional alterations of tumor suppressor genes are expected. Therefore, concomitant genetic changes of p53 and deleted in colon carcinoma (DCC) in pancreatic carcinoma cell lines and primary tumors were analyzed. METHODS: p53 protein and transcript expression were revealed by immunocytochemistry and immunohistochemistry, immunoassay, and Northern blot analysis. p53 mutations were identified by sequence analysis. DCC expression was investigated by reverse transcription polymerase chain reaction. RESULTS: p53 overexpression was observed in 9 of 12 cell lines. p53 point mutations were confirmed in seven cell lines overexpressing p53. The majority of cell lines showed concomitant p53 and DCC alterations. Four of 6 primary tumors overexpressing p53 also showed loss of DCC expression. CONCLUSIONS: p53 and DCC genetic changes are associated with pancreatic cancer and the frequently activated c-Ki-ras oncogene. Therefore, the multihit model of carcinogenesis could prove relevant for pancreatic cancer. PMID- 8194713 TI - Contractile mechanisms of gallbladder filling and emptying in dogs. AB - BACKGROUND/AIMS: The mechanisms of gallbladder filling and emptying during the fasting state, postprandial state, and after intravenous administration of cholecystokinin, motilin, and morphine were investigated in conscious dogs. METHODS: Bile flow in the cystic and common bile ducts was measured by miniature flow probes. RESULTS: The gallbladder showed brief alternating excursions of filling and emptying in the fasting and fed state. The emptying excursions exceeded the filling excursions during phase II and for about 4 hours after a meal. The filling excursions exceeded the emptying excursions during phase I, phase III, and the latter half of the postprandial state. Most gallbladder emptying occurred when its pressure was high, and most filling occurred when its pressure was low. The duodenal contractions played a major role in gallbladder filling and emptying during phase III. CONCLUSIONS: Gallbladder filling and emptying are not monotonous during the fasting and postprandial states. The brief alternating excursions of filling and emptying would almost continually mix the concentrated gallbladder bile with the fresh dilute hepatic bile to prevent supersaturation of the gallbladder bile during the fasting state and extend the delivery of a small volume of concentrated gallbladder bile for a period of several hours after a meal. PMID- 8194715 TI - Liver hemorrhage: recurrent episodes during pregnancy complicated by preeclampsia. AB - Intrahepatic hemorrhage with rupture is the most serious and potentially life threatening liver complication of pregnancy. With improved management, more patients are surviving this complication, and therefore, a number of patients are at risk of a recurrence should they again become pregnant. This case describes a patient who suffered two episodes of intrahepatic hemorrhage in two different pregnancies. Each episode was associated with mild preeclampsia. The first hemorrhage was limited by the liver capsule and treated conservatively, whereas with the second hemorrhage, the subcapsular hematoma ruptured, requiring arterial embolization followed by surgery. An arteriogram performed during the second episode of hemorrhage showed numerous pseudoaneurysms in the area of bleeding, suggesting that a vasculopathy plays a primary role in the pathogenesis of the intrahepatic hemorrhage associated with pregnancy. This case shows that intrahepatic hemorrhage may recur with future pregnancies, and individuals who suffer this complication of pregnancy and again become pregnant should be carefully monitored for the development of preeclampsia. PMID- 8194714 TI - Gallbladder contractility in aspirin- and cholesterol-fed prairie dogs. AB - BACKGROUND/AIMS: Whether aspirin prevents cholesterol gallstone formation is controversial. This study aimed to investigate this issue and determine the depression of gallbladder smooth muscle contractility associated with cholesterol feeding in the prairie dog. METHODS: Prairie dogs were divided into four subgroups. Animals were fed control or 1.2% cholesterol diet and treated with placebo or aspirin for 2 weeks. The presence of crystals and stones was determined, and contractile force in response to cholecystokinin octapeptide (CCK 8) of gallbladder muscle strips was measured. RESULTS: Maximal stress of 2.66 +/- 0.23 x 10(4) N/m2 was measured in muscle strips from animals on control diet. Maximal stress was significantly lower in strips from animals on high-cholesterol diet, being 1.49 +/- 0.16 x 10(4) N/m2 with placebo and 1.62 +/- 0.23 x 10(4) N/m2 with aspirin. The difference in maximal stress between aspirin-treated and placebo-treated animals was not significant. Although none of the animals on control diet had crystals or stones, all animals on the high-cholesterol diet, whether receiving placebo or aspirin, had crystals in the bile, and more than 65% had cholesterol stones. CONCLUSIONS: Aspirin has no effect on stone formation, nor does it prevent the decrease in contractility despite a profound decrease in endogenous gallbladder prostanoid synthesis. PMID- 8194716 TI - Primary and secondary liver/kidney microsomal autoantibody response following infection with hepatitis C virus. AB - Liver/kidney microsomal autoantibody type 1 (LKM-1), which characterizes a subtype of autoimmune hepatitis, is also found in some patients with chronic hepatitis C virus (HCV) infection. Whether HCV and LKM-1 are accidentally or causally related is unknown. This case report describes a child who became infected by HCV after liver transplantation for end-stage liver disease caused by alpha 1-antitrypsin deficiency. LKM-1 was detected by immunofluorescence, anti microsomal reactivity by Western blotting, anti-HCV and anti-GOR by immunoenzymatic assays, and HCV RNA by polymerase chain reaction. Two weeks after HCV infection, immunoglobulin (Ig) M LKM-1 appeared, followed by IgG1 LKM-1, with titers increasing to 1/2560; antibodies to a 50-kilodalton liver microsomal protein appeared 2 months later. Sera from day 1 posttransplant became positive for HCV RNA. HCV RNA was also detected in a liver biopsy specimen obtained 3 months after surgery. The patient did not produce anti-HCV and anti-GOR antibodies throughout the study and had no histological evidence of hepatitis. The temporal relationship between HCV infection and LKM-1 production suggests that HCV may trigger a primary autoimmune response. The lack of liver damage attributable to autoimmunity or viral infection may be caused by immunosuppression. PMID- 8194717 TI - Immunogenetics of chronic liver diseases. AB - The genetic background of autoimmune diseases becomes more and more evident. Immunogenetics comprises the analysis of genes and their products located at the region 6p21 on the short arm of chromosome 6, which is also known as the major histocompatibility complex (MHC). MHC class I and II genes are highly polymorphic. The complement genes C2, C4A, C4B, and BF, which are also polymorphic, became known as MHC class III genes. In autoimmune hepatitis type 1, there is a dual association for white persons with either HLA-A1-B8-DR3 or HLA DR4. In patients from Japan, autoimmune hepatitis type 1 is predominantly associated with HLA-DR4. This dual association is confirmed at the DNA level. Whereas only limited data are available for autoimmune hepatitis type 2, the association of primary biliary cirrhosis with HLA-DR8 is based on several studies. Primary sclerosing cholangitis is associated with HLA-B8-DR3 and -DR52a. This association was confirmed at the DNA level because of a significant increase of the DRB3*0101 allele. For DRB3*0101-negative individuals, a second association with DRB5*0101 (= DR2) was described. Further analysis of the hypervariable region of the HLA class II molecule indicates that lysine at position 71 is crucial for autoimmune hepatitis type 1 in white persons, whereas position 13 is important for people from Japan. In contrast, leucine at position 35 is important for patients with primary biliary cirrhosis, whereas leucine at position 38 is an important risk factor for primary sclerosing cholangitis. The MHC class III allele C4A-QO is significantly increased in autoimmune hepatitis type 1 and 2 and in primary biliary cirrhosis. Advances in immunogenetics will certainly increase our knowledge of the etiology and pathogenesis of immune-mediated liver diseases, which hopefully will lead to more specific therapeutic interventions. PMID- 8194718 TI - L-Glutamine in intestinal sodium absorption: lessons for physiology, pathobiology, and therapy for diarrhea. PMID- 8194719 TI - Targeting colonoscopy. PMID- 8194720 TI - New paradigms for the pathophysiology of infectious diarrhea. PMID- 8194721 TI - p53: tumor suppression through control of the cell cycle. PMID- 8194722 TI - Gene therapy for exocrine pancreatic insufficiency. PMID- 8194723 TI - Do we understand how surgery prevents gastroesophageal reflux? PMID- 8194724 TI - Pain and an intact gallbladder: is the sphincter of Oddi to blame? PMID- 8194725 TI - A mechanism for esophageal tumor-derived immunosuppression. PMID- 8194726 TI - A new endoscopic procedure provides insight into an old disease: acute acalculous cholecystitis. PMID- 8194727 TI - Diagnostic gold standard for chronic hepatitis. PMID- 8194728 TI - Somatostatin-receptor scintigraphy in endocrine tumors. PMID- 8194729 TI - Alcoholics' impaired lymphocyte response is caused by alcohol. PMID- 8194730 TI - "H2 nonproducers" and malabsorption of carbohydrate. PMID- 8194731 TI - Anti-inflammatory activity without NSAID-related gastropathy. PMID- 8194732 TI - Microscopic colitis: a "transatlantic" unifying concept. PMID- 8194733 TI - Interactions between protein kinase C and arachidonic acid in the gonadotropin response to salmon and chicken gonadotropin-releasing hormone-II in goldfish. AB - Previous studies have shown that, in goldfish, the gonadotropin (GTH) response to salmon GTH-releasing hormone (sGnRH) is partly mediated by arachidonic acid (AA) metabolism via the lipoxygenase enzyme system, whereas protein kinase C (PKC) participates in both sGnRH- and chicken (c)GnRH-II-induced GTH secretion. In this study, the interactions between AA- and PKC-dependent pathways in mediating the long-term GnRH stimulation of GTH release were further investigated using dispersed goldfish pituitary cell cultures in static incubation. Treatments with AA or the PKC activator tetradecanoylphorbol acetate (TPA) increased GTH release. The GTH responses to AA and TPA were additive. The lipoxygenase inhibitor nordihydroguairetic acid (NDGA) and the PKC inhibitor H7 selectively reduced AA- and TPA-stimulated GTH release, respectively. These findings suggest that the GTH responses to stimulation by AA- and PKC-dependent signaling pathways are independent of one another. In other experiments, the GTH response to cGnRH-II was unaffected by NDGA but was abolished by H7. In contrast, sGnRH-induced GTH release was attenuated by NDGA and H7. Furthermore, in the presence of both NDGA and H7, the GTH response to sGnRH was abolished. These data suggest that sGnRH stimulation of GTH secretion involves both AA- and PKC-dependent mechanisms; in contrast, cGnRH-II action is not dependent on AA metabolism. The pathway by which AA might be mobilized in response to a GnRH challenge was also investigated by pharmacological manipulations. The diacylglcerol (DG) lipase inhibitor, U-57908, did not decrease sGnRH- and cGnRH-II-induced GTH secretion. On the other hand, the phospholipase A2 (PLA2) inhibitors, bromophenacyl bromide (BPB), chloroquine, and quinacrine, reduced sGnRH-elicited, but not cGnRH-II-stimulated GTH release. The addition of AA reversed the inhibitory action of BPB on sGnRH-elicited GTH release. In addition, the GTH response to AA was additive to the cGnRH-II induced, but not the sGnRH-elicited GTH release. Together, these findings indicate that sGnRH-induced AA mobilization probably involves activation of PLA2 but not DG lipase. These results also support the hypothesis that the AA signaling component is much less important in mediating the long-term cGnRH-II stimulated GTH secretion, as compared to sGnRH-elicited GTH release. PMID- 8194734 TI - Effect of thyroid hormone on developmental transition of myosin light chains during flounder metamorphosis. AB - Thyroidal control of the transition of myosin isoforms during flounder metamorphosis was examined by the administration of either only thiourea (TU), a potent inhibitor of thyroid hormone synthesis, or thyroxine (T4) together with TU into premetamorphic larvae. Immersion of premetamorphic larvae in 400 microM of TU inhibited the appearance of the adult-type DTNB (5,5'-dithio-bis-nitrobenzoic acid) light chain, LC2, whereas administration of T4 with TU induced a precocious appearance of LC2 and decreased the relative amount of the larval-type DTNB light chain, LC2*. TU was administered into juveniles just after completion of metamorphosis. The treatment did not affect the composition of the myosin light chains. These results suggest that thyroid hormone irreversibly turns on the switch for transition of the DTNB light chains from larval to adult type during metamorphosis of the flounder. PMID- 8194735 TI - Insulin-like growth factor-I in the ovary of the laying hen: gene expression and biological actions on granulosa and thecal cells. AB - Concentrations of insulin-like growth factor-I (IGF-I) were measured in granulosa and thecal tissue dissected from the three largest follicles in the ovaries of laying hens. The higher concentration was found in extracts of granulosa (0.82 +/ 0.01 pmol/g wet wt) and theca (0.36 +/- 0.02), both of which were greater than that in liver extracts (0.25 +/- 0.01). RNA was extracted from these tissues, and by using reverse transcription and the polymerase chain reaction with primers specific for chicken IGF-I, both granulosa and thecal tissue were shown to express chicken IGF-I mRNA. Granulosa and thecal cell cultures were established and used to measure IGF binding sites and the response to exogenous IGF peptides in terms of DNA synthesis. Both cell types bound [125I]IGF-I, which was displaced by IGF-I, IGF-II, and insulin in descending order of potency, characteristic of a type-I IGF receptor. Treatment of granulosa and thecal cell cultures with IGF-I resulted in a dose-dependent increase in [3H]thymidine incorporation into DNA by both cell types. LH, but not FSH, stimulated DNA synthesis in cultured granulosa cells but not in cultured thecal cells. This effect was enhanced in granulosa cells by the addition of IGF-I to the culture medium. These data are consistent with an autocrine or paracrine role for IGF-I within the developing ovarian follicle of the domestic hen. PMID- 8194736 TI - Immunocytochemical study of the growth hormone and prolactin pituitary cells in male and female suckling mink. AB - Adenohypophyseal growth hormone (GH) and prolactin (PRL) cells of suckling mink of both sexes at different stages of lactation were studied by the immunogold method and morphometry for electron microscopy. Hypophyses were perfused with fixative, postfixed in osmium tetroxide, and embedded in Epon 812. Ultrathin sections were labeled by the immunogold method with anti-human GH and anti-human PRL sera. Two PRL cell types were identified based on their morphology and the development of cytoplasmatic organelle. Significant differences in the granular sizes of GH and PRL cells were found between males and females at different stages of suckling. The results suggest that the changes in secretion and storage in GH and PRL cells of suckling mink during lactation depend upon sex and age, and that the granular polymorphism is not an unequivocal criterion for the identification of PRL cells in suckling mink. PMID- 8194737 TI - Synthesis, turnover, and release of peptides from the neurohypophysis of the Jerboa Jaculus orientalis. AB - Peptide contents of neural lobes from adult jerboas (Jaculus orientalis) under different states of hydration were determined by radioimmunoassay. The amounts of vasopressin, oxytocin, and their associated neurophysins in animals dehydrated for up to 4 weeks were not significantly different from those of controls. The different neurohypophyseal peptide were separated on two different types of gradient using reverse-phase high-performance liquid chromatography. The shape of the chromatograms suggests that, in contrast to the case of the rat, for which only three types of neurophysins have been shown, there are, in jerboa, many subspecies of neurophysins. This was also shown using two-dimensional electrophoresis. Injection of [35S]cysteine into the supraoptic nucleus followed by HPLC of extracts from the neural lobes from animals under different states of dehydration showed that the labeled material is not released any faster in dehydrated animals than in controls. Labeled vasopressin, oxytocin, and neurophysins could still be detected by HPLC 4 weeks after injection. Neural lobes from animals injected with [35S]cysteine were perfused in vitro and the release of neuropeptides was triggered by bursts of electrical pulses and also by K(+)-induced depolarization. The amplitude of the rate constant for release and the amounts of vasopressin and of radiolabeled material released were similar in animals dehydrated for up to 3 weeks and in controls. Under physiological conditions similar to those that would be expected to occur in their natural habitat, the jerboas appear to have a hypothalamoneurohypophyseal system which is down-regulated. PMID- 8194738 TI - Regional distribution and in vitro secretion of salmon and chicken-II gonadotropin-releasing hormones from the brain and pituitary of juvenile and adult goldfish, Carassius auratus. AB - The content of salmon (sGnRH) and chicken-II (cGnRH-II) gonadotropin-releasing hormones was measured in discrete brain regions and pituitaries of juvenile and postspawning adult goldfish, using specific radioimmunoassays. In juveniles, the content of both peptides was low. sGnRH was the predominant form in telencephalon preoptic area (T-POA) (sGnRH:cGnRH-II ratio = 2.06 +/- 0.66) and diencephalon (DIEN) (sGnRH:cGnRH-II ratio = 2.72 +/- 0.32), whereas cGnRH-II was predominant in cerebellum-brain stem (STEM) (sGnRH:cGnRH-II ratio = 0.47 +/- 0.05). Equal amounts of the two peptides were present in pituitary (PIT) (sGnRH:cGnRH-II ratio = 1.04 +/- 0.18). In adults, the content of both peptides in all regions was significantly increased. The increase in sGnRH exceeded that of cGnRH-II in T-POA and PIT, resulting in an increased sGnRH:cGnRH-II ratio in these tissues (T-POA, 3.55 +/- 0.26; PIT, 7.85 +/- 2.28). In DIEN and STEM, the increase in cGnRH-II content equaled or exceeded that of sGnRH; the sGnRH:cGnRH-II ratio was unchanged in STEM (0.39 +/- 0.06) and decreased in DIEN (1.23 +/- 0.13). The secretion of sGnRH and cGnRH-II was investigated under static in vitro incubation conditions. Both forms of the peptide were secreted from T-POA slices and PIT fragments from juvenile and adult fish. Secretion was significantly increased under potassium depolarizing conditions. Secretion of the two peptides was proportional to their content in tissues from both juvenile and adult goldfish. PMID- 8194739 TI - Seasonal changes in plasma growth hormone and prolactin concentrations of the frog Rana esculenta. AB - Plasma growth hormone (GH), prolactin (PRL), and vitellogenin (VTG) concentrations were determined during the annual reproductive cycle of the frog Rana esculenta. Plasma GH and PRL were measured using a RIA that employed purified bullfrog (Rana catesbeiana) GH and PRL as standards and radioligand, and their respective antibodies. Using ELISA, plasma VTG titers were related to ovarian weight. GH, PRL, and VTG displayed different trends related to season and sex. In male frogs the GH and PRL trends have been found parallel, showing the highest concentrations (35 and 85 ng/ml, respectively) during the winter months. In the female frogs, the GH trend behaved differently from that in males; in fact, plasma GH changed during the annual reproductive cycle, showing two main peaks occurring during the reproductive period and the autumn ovarian recrudescence that are well correlated with the vitellogenesis as well as with the main changes in ovarian weight. PMID- 8194740 TI - The regulation of prolactin cells in the rainbow trout (Oncorhynchus mykiss). 1. Possible roles for thyrotropin-releasing hormone (TRH) and oestradiol. AB - The regulation of rainbow trout prolactin (PRL) cells by hypothalamic and humoral factors has been investigated. PRL cell activity was assessed using acid gel electrophoresis to measure PRL release in vitro and image analysis to measure PRL cell nuclear area, an index of synthetic activity. 17 beta-oestradiol stimulate PRL synthesis and release during a 48-hr incubation. TRH reduced PRL synthesis and release and the use of bacitracin to prevent metabolism reduced the effect on release, though not that on synthesis, suggesting that a metabolite of TRH may have a role, at least in the former process. This was supported by the finding that the TRH metabolite, cyclo(His-Pro), was also potent in inhibiting PRL cell activity; hence, at least part of the action of TRH may be via metabolites. In some experiments, the PRL isoforms, PRLI and PRLII, could be separately measured and their release appeared to be differentially affected by TRH and cyclo(His Pro). A 48-hr pretreatment with 17 beta-oestradiol to stimulate PRL cell activity did not prevent the inhibitory effects of TRH, rather the responses were enhanced. TRH and its metabolite(s) and oestradiol are concluded to regulate rainbow PRL secretion. PMID- 8194741 TI - Growth hormone secretory characteristics of sex-linked dwarf and normal-sized chickens reared on a control or on a 3,3',5-triiodothyronine-supplemented diet. AB - This study examined the pulsatile presence of growth hormone (GH) in the plasma- which reflects its pulsatile release--of 8-week-old male sex-linked dwarf (dwdw) or normal-sized (Dwdw) chickens from a brown-egg layer strain reared on a control or on a 0.5 ppm triiodothyronine(T3)-supplemented diet. The overall GH mean, amplitude, and baseline levels of control dw chickens were significantly higher than those of control Dw chickens. No differences in peak length or peak frequency between genotypes were observed. Dietary T3 supplementation abolished the pulsatile GH release in both genotypes. T3 treatment depressed the mean GH levels of Dw but not of dw chickens. PMID- 8194742 TI - The influence of body condition on 17-beta estradiol levels in relation to vitellogenesis in female Vipera aspis (Reptilia, Viperidae). AB - Seventy-six wild Vipera aspis females were caught over 3 years and placed in outdoor enclosures; 39 reproduced and 37 did not. Almost all the reproductive females had a body condition index (BCI) greater than 0.70 when vitellogenesis began. Monthly blood samples were taken by cardiac puncture. The main plasma parameters of vitellogenesis were measured by spectrophotometry: total plasma calcium, phosphorus, phospholipids, cholesterol, triglycerides, proteins, and albumin. Plasma 17-beta estradiol levels were determined by RIA. Vitellogenesis started soon after hibernation in reproductive females with very high 17-beta estradiol concentrations (average of 4.00 ng/ml) and there was a marked mobilization of maternal reserves (fat bodies, liver, and vertebral bone) associated with very high values of plasma calcium, phosphorus, phospholipids, cholesterol, triglycerides, and proteins. The kinetics of the main plasma components were described throughout the vitellogenesis period (from March to early June), when all plasma parameters differed markedly between reproductive and nonreproductive females. After ovulation, the differences between the two groups of females disappeared except in the case of albumin, which remained at a very low level in reproductive females for 6 months. All nonreproductive females had low 17-beta estradiol plasma levels during vitellogenesis (average of 0.08 ng/ml) and there was no suggestion of mobilization of maternal reserves. After vitellogenesis plasma concentrations of estradiol were low in reproductive (an average of 0.08 ng/ml) and in nonreproductive animals (0.06 ng/ml). Five nonreproductive females kept in the laboratory were estrogenized by 17-beta estradiol silastic implants. The 17-beta estradiol concentrations were close to those measured in reproductive females during vitellogenesis. Maternal reserves were mobilized, with almost all metabolic parameters exhibiting the vitellogenic pattern. When the silastic implants were removed, 17-beta estradiol concentrations dropped sharply to a basal level, but the other components were maintained near the vitellogenic values for several months. In contrast to previous studies on viviparous snakes, these results suggest that in V. aspis 17 beta estradiol levels are linked strictly to vitellogenesis. PMID- 8194743 TI - An analysis of the proopiomelanocortin systems in the pituitary of the squamate reptile Lacerta galloti. AB - Acid extracts of the pars intermedia of the squamate reptile Lacerta galloti were screened for immunoreactive forms of proopiomelanocortin (POMC)-related end products following Sephadex G-50 column chromatography. alpha-MSH-sized end products were detected with a Val-NH2, C-terminal-specific RIA, and beta endorphin-sized end products were detected with a separate C-terminal-directed RIA. Five peaks of alpha-MSH-related immunoreactivity were isolated following fractionation by reversed-phase HPLC. Based on a comparison of the reversed-phase HPLC properties and the net positive charges (pH 2.75) of the Lacerta forms of alpha-MSH to those of the mammalian forms of alpha-MSH and Anolis carolinensis ACTH(1-13)NH2, it appears that the N-acetylation of alpha-MSH is a major post translational processing event in the pars intermedia of L. galloti. Although multiple forms of beta-endorphin were detected in the pars intermedia of L. galloti following cation-exchange chromatography, the low levels of N-acetylated beta-endorphin detected with an N-acetyl-specific beta-endorphin RIA indicate that the N-acetylation of beta-endorphin in this species is a minor post translational processing event. This pattern of POMC processing in the pars intermedia of L. galloti is similar to the processing events observed for the turtle Pseudemys scripta, but distinct from the processing events observed in the squamate reptile A. carolinensis. PMID- 8194744 TI - Protein synthesis and ecdysteroidogenesis in prothoracic glands of the tobacco hornworm (Manduca sexta): stimulation by big prothoracicotropic hormone. AB - The 28-kDa size variant of prothoracicotropic hormone (big PTTH) stimulates ecdysteroidogenesis by prothoracic glands of Manduca sexta. In the present studies, big PTTH stimulated in vitro incorporation of [35S]methionine into proteins of prothoracic glands from Day 7 last instar larvae. In 2-hr incubations, big PTTH elicited an approximately 2-fold increase in total protein specific activity. The effect appeared to be tissue specific, as big PTTH had no effect on incorporation of label into proteins of control tissue (fat body). Electrophoretic separation of tissue homogenates, followed by autoradiography and densitometric analysis, revealed increased incorporation of radiolabel into numerous glandular proteins. The result suggested that the effect of big PTTH was a general stimulation of protein synthesis, not specific stimulation of a subset of glandular proteins. Big PTTH-stimulated ecdysteroidogenesis was inhibited by cycloheximide, indicating that the increase in protein synthesis is a requisite for enhanced hormone production. Analysis of gland incubation media revealed numerous radiolabeled proteins. The effect of big PTTH on incorporation of [35S]methionine into media proteins was considerably more variable than the effect of big PTTH on tissue incorporation. The result is consistent with the hypothesis that prothoracic glands may release proteins in addition to ecdysteroids. PMID- 8194745 TI - Effect of photoperiod, testosterone, and estradiol on body mass, bifid claw size, and pelage color in collared lemmings (Dicrostonyx groenlandicus). AB - Collared lemmings undergo several photoperiod-mediated seasonal physiological changes. When exposed to short photoperiod, lemmings increase in size, develop a bifid claw, and molt to a white pelage. Previous data indicate that body mass, claw size, and pelage color are influenced by hormones of testicular origin, suggesting that, on a seasonal basis, changes in production of, or sensitivity to, testicular hormones may play a role in the development of the phenotype characteristic of the ambient photoperiod. The present study was designed to determine if the active testicular hormone(s) is testosterone (T) and/or estradiol (E2) and if seasonally changing physiological traits in female lemmings are also influenced by gonadal status. Fifty-day-old lemmings, reared in 22L:2D (long day), 16L:8D (intermediate day), or 8L:16D (short day), were either gonadectomized or sham operated and given either empty Silastic implants or implants containing T (4 or 10 mm; castrated males), E2 (4 mm undiluted or diluted 1:4 with cholesterol; ovariectomized females), the aromatase inhibitor ATD (androsta-1,4,6-triene-3,17-dione; 2 x 20 mm; intact animals of both sexes), or ATD plus a 10-mm T implant (castrated males). After a 6-week treatment period, changes in body mass, bifid claw width, pelage color stage, and serum prolactin (PRL) were assessed. The effects of gonadectomy and steroid treatment depended upon photoperiod. Whereas gonadectomy increased mass gained by both sexes under intermediate and short day, under long day only females showed the positive mass response to gonadectomy. Treatment with T and E2 reversed the effect of gonadectomy on body mass under intermediate day and decreased the amount of mass gained under short day. Treatment with ATD (males) and E2 (females) indicated that E2 was the hormone responsible for the tonic, inhibitory effect of the gonads on body mass in both sexes. Claw size was most sensitive to steroid manipulation in animals housed in long day, in which all treatments had a negative influence. Gonadectomy under short day resulted in the development of a whiter pelage in both sexes. The effect of gonadectomy on pelage in female lemmings, and its reversal by E2 treatment, may have been partially due to alteration of serum PRL. PMID- 8194746 TI - Signal transduction in avian granulosa cells: effects of protein kinase C inhibitors. AB - We evaluated the effects of two protein kinase C (PKC) inhibitors, staurosporine (ST) and H-7, on LH-activated phospholipase C and adenylate cyclase activity by measuring the production of inositol phosphates (IP) and cAMP in freshly dispersed granulosa cells from mature preovulatory follicles of laying hens. ST and H-7 dose-dependently potentiated LH-stimulated IP generation, whereas a protein kinase A (PKA) inhibitor (H-8) had no effect. The PKC activator, phorbol ester TPA (50 nM), significantly inhibited LH-stimulated IP production, which was completely prevented by ST. Both ST and H-7, while having no effect on basal cAMP levels, significantly and dose-dependently potentiated LH-stimulated, but not forskolin-stimulated cAMP production. However, progesterone production in response to LH, forskolin, and 8-Br-cAMP was inhibited in granulosa cells preincubated for 30 min with H-7 or ST. H-7 and ST had no effect on 25 hydroxycholesterol- and pregnenolone-supported progesterone production. These results support a negative feedback role for PKC in LH-initiated signal transduction in avian granulosa cells. PKC blockade removes the inhibitory effect on LH-stimulated phospholipase C and adenylate cyclase activity. The inhibitory effect of H-7 and ST on progesterone synthesis could be attributed to inhibition of PKA and/or steps proximal to cholesterol side-chain cleavage. PMID- 8194747 TI - The role of the 3'-untranslated region of non-polyadenylated plant viral mRNAs in regulating translational efficiency. AB - Tobacco mosaic virus (TMV) is a positive-sense RNA virus in which the single genomic RNA functions as a messenger RNA. It is a member of a class of plant viral RNAs that are the only known non-polyadenylated mRNAs in plants. The 3' untranslated region (UTR) of TMV genomic RNA is the functional equivalent of a poly(A) tail in that it increases mRNA stability and regulates translational efficiency. To determine whether the 3'-UTR of other non-polyadenylated plant viral mRNAs regulate translation, those from turnip yellow mosaic (TYMV), brome mosaic (BMV), and alfalfa mosaic (AlMV) viruses were investigated. Chimeric gene constructs were made in which the viral 3'-UTRs were introduced immediately downstream from the reporter genes encoding beta-glucuronidase (GUS) and luciferase (LUC), and were translated in plant protoplasts following delivery of the mRNA using electroporation. The 3'-UTR from BMV RNA3 regulated reporter gene expression in vivo to an extent comparable to that observed for the TMV 3'-UTR. The BMV 3'-UTR increased both message stability and translational efficiency. As regulators of translation, the BMV and TMV 3'-UTR were dependent on the presence of a cap at the 5' terminus for function. The 3' UTR of TYMV or AlMV RNA4 had little impact on translation or transcript stability. These data suggest that although the TMV 3'-UTR is not unique in regulating translation, the 3'-UTR of plant viral mRNAs do vary in their regulatory ability. PMID- 8194748 TI - Expression of foreign genes in cultured human primary macrophages using recombinant vaccinia virus vectors. AB - Recombinant vaccinia viruses (re-VVs) provide an extremely versatile method for the expression of foreign genes in a wide range of cultured cell types of different lineages and species. In the present report, we examine the utility of re-VV vectors for re-protein production in cultured human primary macrophages obtained through in vitro differentiation of peripheral blood monocytes. Primary macrophages supported early stages of the VV infection cycle, including morphologic cytopathic effect, shut-off of host protein synthesis and activation of early viral protein synthesis; however, late stages of infection were blocked, including synthesis of late viral proteins, replication of viral DNA, and production of infectious progeny virions. Abortive infection was observed with several independent VV strains. Using re-VVs containing Escherichia coli lacZ as a reporter gene, we assayed the activities of different classes of VV promoters. Consistent with the results noted above, human primary macrophages supported reporter gene expression driven by an early or intermediate VV promoter, but not by a late promoter; expression was obtained with synthetic bifunctional promoters containing early and/or intermediate components. Primary macrophages also supported the VV/bacteriophage T7 RNA polymerase hybrid gene expression system. The utility of re-VV vectors for production of proteins of biological interest in human primary macrophages was demonstrated using re-VVs encoding human CD4 and the human immunodeficiency virus type-1 envelope glycoprotein. PMID- 8194749 TI - Three novel SMR1-related cDNAs characterized in the submaxillary gland of mice show extensive evolutionary divergence in the protein coding region. AB - We have previously characterized an abundant male-specific mRNA from the submaxillary gland (SMG) of rats, encoding the SMR1 (androgen-regulated) protein, which has the structure of a prohormone and is processed by maturation enzymes to release a small peptide in the blood and saliva. We have now characterized three SMR1-related cDNAs in the SMG of Balb/c mice. These cDNAs encode three novel proteins, designated MSG1, MSG2 and MSG3. They are 639, 662 and 471 nucleotides (nt) long, respectively, and the corresponding mRNAs appear to be expressed only in the SMG. The putative polypeptides they encode carry an N-terminal secretory peptide sequence and are, therefore, presumably secreted into saliva. Although closely related, the three mRNAs show striking differences: a particularly different expression pattern and an extremely high degree of variability observed in the central part of the molecules. The MSG1 and MSG3 cDNAs are identical, except for a 173-bp insert found only in MSG1. This insert contains three Pro rich repeats (GPGIGRPPPPPP), reminiscent of the most abundant multigenic family of the SMG, the Pro-rich proteins (PRP). Although MSG1 shares several common features with PRP, it is structurally related to SMR1. The unusually high ratio of replacement/silent nt changes provides a basis to address complex aspects concerning the molecular events leading to the emergence of new proteins in the SMG. PMID- 8194750 TI - The mouse Rxrb gene encoding RXR beta: genomic organization and two mRNA isoforms generated by alternative splicing of transcripts initiated from CpG island promoters. AB - Two major isoforms of retinoid X receptor beta (RXR beta; H-2RIIBP), encoded by the Rxrb gene, have been identified in the mouse. Northern analysis of Rxrb mRNA showed two close bands of 2.8 and 2.6 kb in many tissues and cell lines. They are designated as mRxr beta 1 and mRxr beta 2, respectively. Some rapidly growing cell lines and spleen tissue had about twofold more Rxr beta 1 mRNA than Rxr beta 2 whereas most adult tissues had similar amounts of both beta 1 and beta 2. Amino acid (aa) sequences deduced from cDNAs show an extra N-terminal domain of 72 aa for RXR beta 1 that is well conserved between mouse and human, but not found in RXR beta 2. These isoforms are generated from separate exons transcribed from different CpG island promoters and spliced into the common acceptor site in the transactivation domain by an alternative splicing. The Rxrb gene contains an intron in the midst of the first zinc-finger coding region. This is different from the retinoic acid receptor (RAR) and other nuclear receptor superfamily genes that contain an intron between the first and the second zinc-finger coding regions. These results, together with their unique ability to form heterodimers with other members of the superfamily, suggest a distinct phylogenic position for the Rxr genes. PMID- 8194751 TI - The cDNA sequence and characterization of the Ca2+/calmodulin-dependent protein kinase-Gr from human brain and thymus. AB - We have isolated and sequenced cDNAs encoding Ca2+/calmodulin-dependent protein kinase type Gr (CaM-K-Gr, also called CaM-K-IV) from human brain and thymus. The sequence of the protein coding region of the cDNA is identical in both brain and thymus, although Northern hybridization analysis shows variation of the mRNA transcripts in these tissues. The sequence predicts a protein of M(r) 51,897 that is 83.7% identical and shows 89.2% similarity with the rat homologue. The deduced human CaM-K-Gr is identical to the rat and mouse proteins in the portion of the enzyme involved in ATP binding, the catalytic domain and Ca2+/calmodulin-binding domain; however, the N terminus of the human kinase, which may comprise a second regulatory domain [McDonald et al., J. Biol. Chem. 268 (1993) 10054-10059], contains a 4-amino-acid (aa) insertion relative to the rodent enzymes. Additionally, the C-terminal association domain shows only 45.2 and 41.6% identity with the rat and mouse proteins, respectively, suggesting that this domain is not constrained by stringent structural and functional requirements. Based on the predicted aa sequence of the human kinase, we produced polyclonal antisera against a C-terminal peptide that recognizes two forms of CaM-K-Gr in human T-cell lymphoma and neuroblastoma cell lines. The human antiserum cross reacts with the rat and mouse proteins and immunoprecipitates the active kinase. PMID- 8194752 TI - The use of overlapping and tailed short primers in the chromosomal assignment of short cDNAs by the polymerase chain reaction. AB - For the PCR-based chromosomal assignment of very short cDNA fragments specifically designed primers are required. We tested primers with very short core sequences that are identical or complementary to known cDNA sequences, with or without tails at the 5' ends. The lower limit of the core length for PCR using human chromosome templates was 14 nucleotides (nt) when they have tails. The minimal length of the tail was 2 nt when it was attached to the 5' end of a 14-nt core. In the absence of a tail, 15 nt are needed for the core to act properly. The overall size of the short cDNA fragments that could be assigned was further reduced by using a pair of primers that overlap at the 3' ends. The limits of the free energy of overlap were about -1.9 kcal/mol at 45 degrees C, -2.9 kcal/mol at 50 degrees C and -4.5 kcal/mol at 55 degrees C. A combination of these features in a primer pair allowed cDNA fragments as short as 30 nt to be assigned. PMID- 8194753 TI - Cloning and sequence analysis of rhp51+, a Schizosaccharomyces pombe homolog of the Saccharomyces cerevisiae RAD51 gene. AB - A homology (rhp51+) of the RAD51 gene in Schizosaccharomyces pombe was cloned by screening a Sz. pombe genomic library using the 3'-end of RAD51 from Saccharomyces cerevisiae as a probe. As in S. cerevisiae, the sequence of rhp51+ showed two MluI cell-cycle boxes and a putative DNA damage-responsive element in its upstream region. The open reading frame codes for a 365-amino-acid (aa) polypeptide with an estimated molecular mass of 40,555 Da. The deduced aa sequence shows 27, 66, 75 and 80% identity with Escherichia coli RecA, S. cerevisiae Rad51 and the Rad51 homologs from chicken and humans, respectively. The aa sequence encoded by rhp51+ contains A- and B-type nucleotide-binding consensus sequences, as found in other RAD51 homologs. Northern blot analysis showed that rhp51+ encodes a 1.7-kb transcript. Methyl methanesulfonate treatment increased the level of this transcript three- to fivefold. Southern hybridization analysis suggests that a single copy of rhp51+ exists in the Sz. pombe genome. PMID- 8194754 TI - The ARG4 gene of Candida albicans. AB - The DNA sequence of a Candida albicans genomic fragment known to complement the arginine mutation designated arg57 in strain 1006 contains an ORF of 1404 nucleotides (nt) predicting a protein of 468 amino acids (aa). Database searches indicated that the deduced protein shares 75% identity and 85% similarity with the ARG4 protein of Saccharomyces cerevisiae. Analysis of the percent aa identity between C. albicans and S. cerevisiae sequences included in available databases suggested these values are within the range expected for biosynthetic enzymes from the two organisms which share similar function. Experiments to isolate C. albicans ARG4 by complementation in an arg4 strain of S. cerevisiae yielded a plasmid (pARG4-1) with a restriction map identical to that of the sequenced clone. From these data, we conclude that the gene previously designated ARG57 is in fact ARG4 encoding the enzyme argininosuccinate lyase (ASL). These results were unexpected, since ARG57 had been localized to chromosome 7, while a mutation causing an ASL deficiency had been linked to ade1, which is on chromosome R. Transformation of C. albicans strains with pARG4-1 indicated it complemented the arginine auxotrophy in strains TMSU221 and 1435, a derivative of 1006. Examination of commonly utilized C. albicans arginine auxotrophs by spheroplast fusion analysis indicated these strains comprise two complementation groups: one consisting of 1006 and TMSU221, which are arg4, and the other of A642, hOG318, hOG357, FC18-6 and WC-5-4, which possess an undefined defect in the arginine biosynthetic pathway which we designate arg100. PMID- 8194755 TI - A simple and efficient system for targeting DNA to the am locus of Neurospora crassa. AB - We have developed a system of recipient strains and donor plasmids that allows targeting of DNA sequences to the am locus of Neurospora crassa. A recipient strain was constructed that contains the 3' two-thirds of the bacterial Hygromycin B (Hy) phosphotransferase-encoding gene (hph) in single copy downstream from the am structural gene encoding NADP-specific glutamate dehydrogenase. Plasmids have been constructed that contain am, but with the 5' end of hph downstream from am. Resistance to Hy can occur during transformation only if recombination occurs within the region of overlap of the hph sequences from the transforming DNA and of the chromosomal hph sequences. A lacZ alpha gene with a multiple cloning site has been inserted into the region between the am and hph sequences to facilitate subcloning into the targeting vector. Additionally, unique sites at the junctions of the vector and targeting DNA allow easy removal of vector sequences prior to transformation. A second recipient strain has been constructed that has had the am structural gene deleted. This strain may be used to provide a double selection for homologous integration. Additionally, this strain facilitates replacement of am with heterologous constructs, including constructs that drive transcription of am with different promoters. The insertion of hph downstream from am has no apparent effect on am expression, and the resistance segregates as a Mendelian factor in crosses. Transformation efficiency is reduced two to three orders of magnitude, but interestingly, nearly all of the resistant strains have only a single copy of the transforming DNA. PMID- 8194756 TI - Characterization of the mnp2 gene encoding manganese peroxidase isozyme 2 from the basidiomycete Phanerochaete chrysosporium. AB - The nucleotide (nt) sequence of a gene (mnp2) encoding manganese peroxidase isozyme 2 (MnP-2) from Phanerochaete chrysosporium was determined. The sequence of 3297 bp includes 1287 bp of 5'-flanking sequence and 490 bp 3' to the stop codon. Comparison of cDNA and genomic sequences indicates seven introns varying in size from 50-55 bp. The 5' upstream region of the mnp2 gene contains a TATAA element, three inverted CCAAT elements (ATTGG), six putative heat-shock elements (HSE) and three putative metal response elements (MRE) (TGCRCNC), all located within 1100-bp upstream from the start codon. The positions of the putative HSE and MRE in the promoter region of mnp2 are compared with the corresponding sequences in the mnp1 gene promoter. A Northern blot probed with a fragment specific for the mnp2 gene suggests that the transcription of mnp2 is regulated by Mn ions. PMID- 8194757 TI - A histone H4 promoter for expression of a phleomycin-resistance gene in Phanerochaete chrysosporium. AB - In this study, two transformation vectors (pMG101 and pMG103) for Phanerochaete chrysosporium were constructed, based on the ble phleomycin-resistance-encoding gene and a homologous histone H4 promoter. Transformation frequencies were 6-10 per micrograms of DNA. Transformed vector DNA could either exist as an unstable replicating plasmid or could be stably integrated. Integrated vector DNA from pMG101, which also contains a histone-encoding H3 gene in the promoter fragment, becomes methylated, resulting in inactivation of ble-dependent resistance. Plasmid pMG103, which lacks the H3, does not show methylation. PMID- 8194758 TI - Trypanosoma cruzi ribosomal DNA: mapping of a putative distal promoter. AB - The nucleotide (nt) sequence (2106 bp) of a cloned rDNA (encoding ribosomal RNA) spacer region from Trypanosoma cruzi was determined and a putative transcription start point (tsp) was mapped. The assigned length for the transcribed spacer is 1768 bp and its tsp is present 270-bp upstream from an alternative tsp published for the equivalent gene from another T. cruzi strain [Dietrich et al., Gene 125 (1993) 103-107]. Sequence comparisons of the nt flanking both T. cruzi tsp with the homologous regions from both other trypanosomatids, and other eukaryotes, indicate that these sequences are poorly conserved within the family Trypanosomatidae. This finding reinforces the proposal that the speciation of trypanosomatids may have occurred early in evolution. PMID- 8194759 TI - Cloning and sequence determination of the gene coding for the pyruvate phosphate dikinase of Entamoeba histolytica. AB - We isolated three overlapping clones from a DNA genomic library of Entamoeba histolytica strain HM1:IMSS, whose translated nucleotide (nt) sequence shows similarities of 51, 48 and 47% with the amino acid (aa) sequences reported for the pyruvate phosphate dikinases from Bacteroides symbiosus, maize and Flaveria trinervia, respectively. The reading frame determined codes for a protein of 886 aa. PMID- 8194760 TI - Three tandemly repeated 5S ribosomal RNA-encoding genes identified, cloned and characterized from Cryptosporidium parvum. AB - We have characterized the 5S rRNA of Cryptosporidium parvum. The gene (rDNA) encoding this 5S rRNA was identified, mapped, the primary and secondary structures determined, and the copy number estimated. Using a PCR-amplified 5S rDNA as a probe, it was shown that this gene can specifically recognize C. parvum genomic DNA, but not other intestinal and environmental organisms tested. Three repeat units of the 5S rDNA found in genomic C. parvum oocyst DNA are within the 2012-bp EcoRI-HindIII fragment and are identical in coding sequence, but differ in flanking regions. Flanking regions are A+T rich (78-89%). The termination signal for polymerase III consists of five thymidine residues at the 3' end of each of three units. PMID- 8194761 TI - Purification of a recombinant Schistosoma japonicum antigen homologous to the 22 kDa membrane-associated antigen of S. mansoni, a putative vaccine candidate against schistosomiasis. AB - We describe the cDNA cloning, overproduction and purification of a 22.6-kDa antigen from the human blood fluke Schistosoma japonicum. A 777-bp cDNA (C32) was isolated from a S. japonicum lambda ZAPII cDNA expression library immuno-screened with hyperimmune rabbit serum (HRS) raised against soluble adult S. japonicum proteins. The open reading frame of C32 encodes a protein of 191 amino acids (aa) which exhibits 71% identity to a 22.6-kDa membrane-associated antigen of S. mansoni, a putative vaccine candidate for schistosomiasis. We have identified a sequence motif known as an EF-hand calcium-binding domain in both the S. japonicum and S. mansoni aa sequences, suggesting that the 22.6-kDa antigens are able to bind Ca2+. Further, we have, for the first time, obtained the 22.6-kDa antigen in purified, non-denatured, recombinant form, and in sufficient quantity to assess the protective value of the molecule in vaccination/challenge experiments. This was achieved by synthesizing the schistosome antigen with a short polyhistidine tag fused to the N-terminus which was then used for subsequent affinity purification. The recombinant protein was purified under non denaturing conditions using nickel-chelate affinity chromatography. PMID- 8194762 TI - Characterization of a rice gene coding for a lipid transfer protein. AB - The cloning and sequence analysis of a gene that encodes a lipid transfer protein (LTP) from rice is reported. A genomic DNA library from Oryza sativa was screened using a cDNA encoding a maize LTP. One genomic clone containing the gene (Ltp) was partially sequenced and analyzed. The open reading frame is interrupted by an 89-bp intron. From the results of Southern hybridizations, Ltp appears to be a member of a small multigenic family. Transcripts of the corresponding gene were detected in several tissues including coleoptile, leaf, endosperm, scutellum and root. The transcription start point was determined by primer extension. The deduced amino-acid sequence of the Ltp product is shown to be homologous to LTPs from other crops. PMID- 8194763 TI - Isolation and characterization of the Drosophila melanogaster gene encoding translation-initiation factor eIF-2 beta. AB - Drosophila melanogaster cDNA clones encoding the beta subunit of translation initiation factor 2 (eIF-2) were isolated and sequenced. The longest cDNA predicts a protein of 312 amino acids (aa), which possesses a putative RNA binding motif and a highly charged N-terminal region composed of three basic polylysine blocks. The aa sequence comparison of D. melanogaster eIF-2 beta with its human and yeast counterparts demonstrates a high degree of similarity, especially within the C-terminal region. Northern analysis indicates quasi constitutive expression of eIF-2 beta throughout D. melanogaster development. PMID- 8194764 TI - The mouse creatine kinase paired E-box element confers muscle-specific expression to a heterologous promoter. AB - E-box elements, with the CANNTG sequence motif, occur in numerous promoters and enhancers. We evaluated the tissue-specific expression properties of the paired murine E-box element from the mouse muscle creatine kinase (MCK) enhancer in a minimal heterologous promoter construct. A 46-bp fragment containing the paired E box element in its wild-type (wt) configuration conferred high levels of muscle specific expression in transfected embryonic chicken cell cultures. The expression from this paired E-box element was similar to that of the simian virus 40 (SV40) promoter/enhancer, but a 21-bp fragment containing a single E-box was inactive. We conclude that the paired E-box element from the MCK enhancer is sufficient for high levels of muscle-specific expression when placed upstream from a non-muscle TATA element. PMID- 8194765 TI - Chimeric molecules created by gene amplification interfere with the analysis of somatic hypermutation of murine immunoglobulin genes. AB - We used the polymerase chain reaction (PCR) to amplify genes encoding murine immunoglobulin (Ig) lambda light-chain variable (V) regions, using DNA isolated from populations of germinal center B-cells, to study somatic hypermutation at this locus. Sequence analysis revealed that 30% of the amplified products were chimeric molecules consisting of segments of the V lambda 1 and V lambda 2 genes. Furthermore, an amplification- and cloning-associated artifact exchanged sequences between mutational variants of V lambda 1 genes. These PCR artifacts interfere with the analysis of somatic hypermutation of Ig genes. An alternative method that avoids these artifacts is suggested which involves the amplification of individual V lambda genes from single cells. PMID- 8194766 TI - Characterization of a 142-bp fragment of the murine c-fos oncogene promoter upstream of the SIF-binding element. AB - We previously reported that in transformed mouse sarcoma cells of spontaneous origin and in revertants transfected with a fos-cat fusion, the 600-bp c-fos promoter region provides chloramphenicol acetyltransferase activity. In the present study, we investigated the binding of transcriptional factor protein(s) to a region (-503 to -361) upstream of the sis (platelet-derived growth factor) inducible factor (SIF)-binding element. Gel electrophoresis retardation (GER) assay clearly demonstrated the appearance of strong binding activity to a newly described fragment in the 142-bp region studied. Further analysis using synthetic oligodeoxyribonucleotides and GER defined a binding region of 30 bp (AvaI-AvaII) from -503 to -472 that partially overlaps with a region known to bind fos promoter binding site 2 (FBS2). DNase I footprint analysis discovered a novel sequence in the upstream region of the c-fos promoter to which protein(s) in nuclear extracts from various mouse and human cells bind. This factor(s) is not identical to most known transcriptional factors present in the promoter region of nuclear oncogenes. A proximal part of this fragment is very conservative and contains several AP-2-like-binding sites. PMID- 8194767 TI - Characterization of 5S rRNA genes from mouse. AB - In order to characterize the transcriptional regulation of the 5S rRNA genes we have isolated a bona fide gene and a pseudogene from mouse cells. These 5S rRNA genes contain a 12-bp sequence designated as the D-box, located in position -33 to -22 bp, and two Sp1-binding sites in the 5'-flanking region. The D-box is conserved in human and hamster 5S rRNA genes although in slightly different upstream positions. The bona fide mouse 5S rRNA gene was transcribed in a HeLa S 100 extract. The transcriptional activity of this gene was only 50% of that of the human gene, indicating the involvement of species-specific transcription factors and/or polymerases. The pseudogene which contains the D-box, but with position +25 to +35 bp deleted, showed no transcriptional activity. Deletion of the D-box in the 5'-flanking sequence abolished transcriptional activity, indicating that this conserved sequence is of importance for gene expression. PMID- 8194768 TI - Cloning of a cDNA encoding a mouse homolog of the interleukin-8 receptor. AB - A mouse cDNA library was screened using a DNA fragment generated by polymerase chain reaction (PCR) with oligodeoxyribonucleotide primers which were derived from the conserved sequences in cDNAs encoding the human and rabbit interleukin-8 receptors (hIL-8R and rIL-8R). A novel cDNA was obtained encoding 359 amino acids (aa) with seven putative transmembrane portions similar to hIL-8R and rIL-8R. Its aa sequence shows 64 and 69% homology to those of type-1 and type-2 hIL-8R, respectively. COS-7 cells transfected with the isolated cDNA in a mammalian expression vector bind IL-8, but do not bind a related protein, monocyte chemotactic and activating factor, suggesting that the isolated cDNA encodes the mouse homolog of IL-8R. Northern blot analysis showed that mRNA of this clone was highly expressed in mouse peritoneal neutrophils, and the single band was observed in Southern blotting analysis on mouse genomic DNA digested with HindIII or KpnI, suggesting that this is a single-copy gene. PMID- 8194769 TI - Sequence of a human cDNA encoding phosphatidylinositol transfer protein and occurrence of a related sequence in widely divergent eukaryotes. AB - Phosphatidylinositol (PtdIns) transfer protein (PtdInsTP) is a phospholipid transfer protein that has been detected in all mammalian tissues examined. It catalyzes the transfer in vitro of PtdIns and phosphatidylcholine between membranes in a number of natural and artificial membrane systems and may be involved in secretion in vivo. In previous studies, we isolated and sequenced a cDNA encoding a rat PtdInsTP. A rat cDNA probe was used to isolate clones from a lambda gt11 human testis cDNA library which encoded full-length human PtdInsTP. The cDNA sequence defines a 270-amino-acid, 31.8-kDa protein whose sequence shares 98.9% identity to that of rat, making it one of the most conserved proteins known between the two species. DNA blot hybridization studies suggest that there may be more than one gene encoding this protein in humans. A comparison of rat and human PtdInsTP cDNAs revealed strong sequence similarity (88 and 84%) in portions of the corresponding 5'- and 3'-untranslated regions (UTR) of the rat and human mRNAs. PMID- 8194770 TI - Isolation and characterization of adenovirus-associated VA RNAs of human adenovirus type 7. AB - Two genes for virus-associated VA RNAs in the human adenovirus type 7 (Ad7) genome are compared to Ad2, Ad4, Ad5, simian VA RNAs, and pol III transcripts of Epstein-Barr virus. The newly identified VA RNA-encoding genes of Ad7 contain two relatively conserved intragenic promoter (elements A and B), the double-stranded RNA-dependent protein kinase (PK) active site-binding domain and transcriptional terminators. The conserved features extend to the VA RNA genes of simian and avian origin. PMID- 8194771 TI - Cloning and sequencing of cDNAs encoding the full-length mouse mannose 6 phosphate/insulin-like growth factor II receptor. AB - Overlapping clones encoding the complete coding sequence of the mouse mannose 6 phosphate/insulin-like growth factor II receptor have been isolated from a liver cDNA library and the nucleotide sequence has been determined. The open reading frame encodes a protein of 2482 amino acids that is 89 and 87% identical to the human and bovine receptors, respectively. PMID- 8194772 TI - The sequence of a murine cDNA encoding Ear-2, a nuclear orphan receptor. AB - A 1643-bp cDNA that encodes the mouse Ear-2 orphan nuclear receptor has been isolated from a pituitary cell library. The predicted 389-aa mouse Ear-2 protein bears significant homology to the known human Ear-2 protein especially in the DNA binding domain. PMID- 8194773 TI - Have you ever thought of a memorial service? Families and residents of a long term care facility say good-bye. PMID- 8194774 TI - A telephone hotline to assist users of the minimum Data Set Plus (MDS+). PMID- 8194775 TI - Sexuality and the chronically ill older adult. PMID- 8194776 TI - Collaboration of practitioners and nurse educators in home care nursing. PMID- 8194777 TI - Preventing disease with vitamins. PMID- 8194778 TI - New Rx for influenza A: flumadine. PMID- 8194779 TI - Claiming and promoting our accomplishments. PMID- 8194780 TI - Ensuring successful home tube feeding in the geriatric population. AB - Successful home tube feeding in the elderly patient is realized by careful patient selection and assessment, thorough and comprehensive teaching plans, and adequate follow-up and monitoring. Nutrient delivery through enteral feeding is an important therapy in maintaining nutritional status, thereby improving strength (and mobility) and immune competence, and thus contributing to an improved quality of life. The nurse plays a key role in facilitating the successful transition from the hospital to the home setting--and an even greater role in allowing the patient to remain at home. PMID- 8194781 TI - Syringe feeding: current clinical practice and recommendations. AB - In a survey of directors of nursing services of 101 nursing homes, it was found that 17 homes still used syringes to feed some of their frail residents. Three of these 17 facilities did not have easy access to speech pathologists, and the facility feeding the greatest number of residents by syringe did not use the services of a speech pathologist to assess swallowing. The practice of syringe feeding seems to be going out of favor, but until this practice is no longer used it is hoped that the recommendations in this article will increase the knowledge and awareness of professional nurses, who are often instrumental in coordinating the difficult and complex decision to syringe feed. PMID- 8194782 TI - Skin tears in frail elders: a practical approach to prevention. PMID- 8194783 TI - [Allergic responses to date palm and pecan pollen in Israel]. AB - Date palm (Phoenix dactylifera) and pecan (Carya illinoensis) trees are commonly planted in Israel for fruit, for shade, or as ornamental plants. Pollen grains of both species are allergenic; however, the extent of exposure to such pollen and the incidence of allergic response have not been studied here. We therefore investigated skin-test responses to pollen extracts of 12 varieties of palm and 9 of pecan in 705 allergic patients living in 3 cities and 19 rural settlements. Sensitivity to the pollen extracts of both species was much higher among residents of rural than of urban communities. Moreover, there was a definite relationship between the abundance of these trees in a region and the incidence of skin responders to their pollen. Sensitivity was frequent in settlements rich in these 2 species, such as those with nearby commercial date or pecan plantations. In general, sensitivity to date pollen extracts was lower than to pecan. However, differences in skin responses to pollen extracts of various clones were substantiated. Air sampling revealed that pollen pollution decreased considerably with distance from the trees. At approximately 100 m from a source concentrations of airborne pollen were low. Since planting of male palm and pecan trees in population centers would increase pollen pollution, it should be avoided. PMID- 8194784 TI - [Nissen fundoplication for gastroesophageal reflux in children]. AB - During a 5-year period 50 children, aged 2 months to 15 years, underwent Nissen fundoplication for the management of severe gastroesophageal reflux and were then followed for from 3 months to 5 years. There were no immediate postoperative deaths. 8 patients (16%) died of serious underlying medical conditions during follow-up. The operation was successful in 86.3% in relation to indications for surgery. Postoperative complications specific for fundoplication occurred in 27 (54%) and other complications in 11 (22%). Of those with complications, 71% were treated successfully. The rest developed dumping syndrome which was diagnosed 1 month to 4 years after operation. They were treated with carbohydrate restriction and a special diet, the results of which will be evaluated later. Although Nissen fundoplication is very successful in resolving the indications for surgery, the high rate of postoperative complications demands re-evaluation of the indications for the operation in children. PMID- 8194785 TI - [Surgical treatment of thoracic esophageal diverticula]. AB - Symptomatic pulsion or "true" diverticula of the lower and mid-esophagus (thoracic esophagus) are relatively rare. Associated motility disorders occur in most patients with epi-phrenic diverticula. These functional and obstructive disturbances should be looked for, diagnosed and treated. Surgical intervention such as diverticulectomy might prevent respiratory and nutritional complications and give significant relief of symptoms. We describe our experience in the surgical treatment of a 67-year-old man and 2 women, aged 69 and 73, respectively, with symptomatic thoracic diverticula. PMID- 8194786 TI - [Treatment of fever of unknown origin by homeopathy]. AB - 2 cases of fever of unknown origin (FUO) treated successfully by homeopathy are presented. The purpose is to show the effectiveness of homeopathy as adjuvant therapy for those in whom the full medical diagnostic process, assessment, and treatment are not effective. In a 12-year-old boy fever and abdominal pain persisted for several months despite various medical treatments. All symptoms disappeared following homeopathic treatment. In a 66-year-old man fever and other symptoms also disappeared after such treatment. We emphasize that homeopathy is not a substitute for the full conventional medical diagnostic investigation and treatment of FUO. Homeopathy should only be practiced by medical doctors to avoid, to the greatest extent, diagnostic and therapeutic errors. PMID- 8194787 TI - [Capgras' syndrome with right frontal meningioma]. AB - We present a 43-year-old woman with a right frontal parasagittal meningioma of the brain who developed the delusion that her husband and children had been replaced by doubles (look-alikes). This type of delusion is typical for Capgras' syndrome. After removal of the tumor the delusion disappeared. The majority of such patients are diagnosed as paranoid schizophrenia. However, in the past decade there has been an increasing number of cases in which the etiology is suspected of being organic, involving mainly the right hemisphere. The case presented is unique because it is the first with meningioma as a possible pathogenic factor in the syndrome, as evidenced by the cessation of the delusion when the tumor was removed. PMID- 8194788 TI - [Congenital CMV meningoencephalitis treated with acyclovir]. AB - A 6-week-old infant was admitted because of anorexia, irritability and convulsions. He was born after an uneventful pregnancy and delivery. He was a normal healthy infant with no previous illnesses and had not been on any medication. The mother's medical history was unremarkable. The convulsions continued during hospitalization and investigation led to the diagnosis of CMV meningoencephalitis, based on the presence of IgM anti-CMV antibodies. He was successfully treated with acyclovir and made an uneventful recovery. PMID- 8194789 TI - [Principles of the process of computerization in primary care clinic]. PMID- 8194790 TI - [Penicillamine--friend or enemy?]. PMID- 8194791 TI - [100 years of activity of Jewish physicians born in Eretz-Israel]. PMID- 8194792 TI - [Beginnings of medicine in the Jewish sector of Eretz-Israel--75 years ago]. PMID- 8194793 TI - [According to need or ability? 67 years since the first Kupat Holim Commission of Inquiry and the initiative for a national health insurance law]. PMID- 8194794 TI - [The disease and death of Judah Aristobolus]. PMID- 8194795 TI - [William Osler--clinician and teacher]. PMID- 8194796 TI - [Increasing use of medical services and the family physician as guardian against excessive use]. PMID- 8194797 TI - The role of the octanoic fatty acid in the pathogenesis of the metabolic alkalosis in experimental liver failure. AB - Octanoate was found to stimulate the muscle proteins catabolism in rats with portacaval anastomosis thus increasing the amounts of 3-methylhistidine, creatinine, ammonium and urea in the excreted urine. The intensive decomposition of the endogenous proteins also produced great amounts of HCO3- whose levels increased in both the urine and blood. It is suggested that in hepatic insufficiency octanoate causes metabolic acidosis through: a) more intensive catabolism of the muscle proteins whose decomposition results in greater amounts of HCO3-, b) metabolization of octanoate to HCO3-, and c) inhibition of the ornithine cycle. PMID- 8194798 TI - Body-plethysmographic pressure-flow diagrams in chronic obstructive lung disease. I. Comparative measurements. AB - One hundred patients with various forms of chronic obstructive lung disease were allocated to groups according to their body-plethysmographic pressure-flow diagrams. Group I comprised 30 patients with resistance curves displaying linear relationship between pressure and flow. The second group (n = 30) was formed by patients who had a markedly pronounced hysteresis in the central parts of their resistance curves. Group III consisted of 30 patients who exhibited resistance curves with distended expiratory parts. Group IV's patients (n = 30) had eight shaped resistance curves. The comparative measurements on these 4 types of body plethysmographic pressure-flow diagrams included all kinds of airway resistances, as well as their components and ratios (Raw, Rpeak, R, Raw(in), Raw(ex), R(ex), R(in), Raw/R, Raw(ex)/R(ex), Raw(in)/R(in), Raw(ex)/Raw(in), R(ex)/R(in)). The analysis of the results shows that the quantitative criteria used in the assessment undergo the greatest change in the eight-shaped loops and in those resistance curves whose expiratory parts are considerably distended. The difference between the absolute values obtained by using the basic methods of calculating airway resistance is the greater the weaker is the linear relationship between pressure and flow. PMID- 8194799 TI - Pathogenetic aspects of clinico-electrophysiological differentiation of transient cerebral circulation disorders terminating with a complete clinical recovery. AB - The present study offers a clinico-theoretical, electrophysiological and rheoencephalographic analysis of the brain matter condition and the cerebral hemodynamics of patients with acute cerebral circulation disorders which resolve with a complete clinical recovery. The purposes of the study were (1) to achieve pathogenetic differentiation of the syndromes of transient ischemic attacks (TIA) and reversible ischemic neurologic deficit (RIND) with greater confidence than that achieved by using the clinical criterion of "the neurologic deficit duration" (24 hours for TIAs, three weeks for RIND). (2) to determine the subclinical level in a single case, and (3) to develop a new approach to secondary prophylaxis in such patients. Fifty four patients (30 men and 24 women, mean age 57.2 +/- 1.9 years) presenting with acute ischemic disorders of cerebral circulation at the Clinic of Vascular Cerebral Diseases in the Department of Neurology of Plovdiv Medical University were followed up in the period between 1989 and 1991. On the 5th and 20th days of the episode onset the central latency time (CLT) of an evoked motor potential (MEP) was investigated on the symptomatic and asymptomatic sides. The study also involved rheoencephalography not only of the clinically followed-up population but also of 59 outpatients with TIA, 129 patients with RIND and 38 patients with an ischemic cerebral stroke. The results obtained objectify the differences among the researchers and confirm their views on the most common pathogenetic mechanisms associated with the occurrence and the course of the two forms of cerebral ischemia terminating with a complete clinical recovery. PMID- 8194800 TI - A methodological approach for integral assessment of the immune status. AB - The proposed approach for assessment of the immune status includes investigation of 21 immune indices of the three effector mechanisms of the immune system--the phagocytic activity, the cellular immunity and immunoregulatory cells and the humoral immunity. Standardized reference values for the corresponding immune indices were obtained using a statistical matrix. These values take into consideration the relationships between the immune reactions, thus allowing integral assessment of immune reactivity. This method permits diagnosis of immunodeficient conditions and control of immunocorrecting therapy. It also enables screening studies to be conducted on the immune status of subjects living in ecologically endangered regions. PMID- 8194801 TI - Relationships between blood oxygen parameters in patients with chronic obstructive lung disease. AB - The hemoglobin-oxygen dissociation curve and the relationships between the parameters of tension, saturation, capacity, affinity and concentration of oxygen in the course of respiratory failure in chronic obstructive lung diseases (COLD) were studied. The study included 141 patients divided into four basic groups according to the value of pO2 (a): patients with normoxia, mild, moderate and severe arterial hypoxia. The blood-gas status was determined using the ABL-330 and OSM-3 analyzers (Radiometer A/S, Denmark). It is concluded that: 1. Presence of normoxia (pO2 and sO2 in norm) in COLD patients does not exclude abnormalities in their arterial blood oxygen transport and increased risk of tissue hypoxia. 2. Total oxygen concentration in respiratory failure is relatively stable and "independent" from the stepwise decrease of the arterial pO2, which results from the compensatory increase of the total and effective hemoglobin. 3. There are phase fluctuations of the ctO2/pO2 dissociation curve in the reference interval, expressed in the "lowering" of P50 and p90 in mild hypoxia and the "centering" or "raising" of their values in severe hypoxia. Such fluctuations are more pronounced in the p90 than in the p50. 4. The oxygen extraction tension lowers progressively (without reaching the anaerobic threshold) and the oxygen compensation factor elevates with the pO2 (a) reduction and the arising of hypercapnia and acidemia. 5. The calculated 2,3-diphosphoglycerate (2,3-DPG) concentration values are significantly higher in hypercapnics with COHb > 1% than in those with COHb < 1%. The relationships between hypoxia, oxygen affinity, hemoglobinemia and oxygen affinity as well as the dissociation curve properties in chronic respiratory failure are discussed. PMID- 8194802 TI - Genetico-mathematical analysis of the inheritance pattern of peptic ulcer disease. Direct methods of Weinberg. I. Method of probands and method of siblings. AB - Inheritance of ulcer disease was analyzed genetico-mathematically using two methods: the method of probands and the method of siblings. Families of 351 probands were enrolled in the study: 57 had type II and 27 type III gastric ulcer disease. 267 were with duodenal ulcer disease. The types of gastric ulcer were determined according to H. Johnson. A further 188 families of type I gastric ulcer probands were also studied. However, data from these are not included in the present study because our previous investigation has shown no genetic determination of this type of ulcer disease. The detailed segregation analysis employed in the study does not support the assumption of a monogenic type of disease inheritance. The values obtained for the coefficient of genetic proportion do not substantiate either autosomal-recessive or autosomal-dominant pattern of transmission. This refers both to ulcer disease in general and to the calculation of the coefficient depending on the type of disease and the type of familial predisposition of probands. PMID- 8194803 TI - Glomerular hyperfiltration and serum beta 2-microglobulin used as early markers in diagnosis of autosomal dominant polycystic kidney disease. AB - This study was undertaken to investigate the dynamics of glomerular filtration and serum beta 2-microglobulin in patients with confirmed autosomal dominant polycystic kidney disease (ADPKD) without chronic renal failure (CRF). Twenty five patients (11 women and 14 men, age range 15 to 56 years) with echographically and computer-tomographically proven ADPKD were entered into the study. Glomerular filtration was followed using the 24 hour creatinine clearance and beta 2-microglobulin serum level was measured radioimmunologically using an ABBOTT laboratories kit. 12 patients had a significantly reduced glomerular filtration: 1.01 +/- 0.05 ml/s compared with 2.12 +/- 0.15 ml/l in the control group (P < 0.001). This group of patients also had a significantly increased level of the serum beta 2-microglobulin: 3.54 +/- 0.47 micrograms/l versus 1.42 +/- 0.28 micrograms/l in healthy controls (P < 0.001). Seven of the patients showed normal glomerular filtration and significantly increased beta 2 microglobulin: 2.65 +/- 0.46 micrograms/l (P < 0.05). The glomerular filtration in six of the patients was found to be significantly increased (hyperfiltration) 2.65 +/- 0.04 ml/s (P < 0.001) while their serum beta 2-microglobulin level tended to rise (2.25 +/- 0.3 micrograms/l). We believe that glomerular hyperfiltration combined with the increased level of the serum beta 2 microglobulin can be used as an early marker of ADPKD. PMID- 8194804 TI - Computer tomographic study of patients with inconclusive echographic findings for autosomal dominant polycystic kidney disease. AB - 40 patients (26 children and 14 adults) with clinico-genealogic and echographic evidence of autosomal dominant polycystic kidney disease (ADPKD) were subjected to a conventional noncontrast computer tomography (CT) of the kidneys. In children, computer tomography proved to be more sensitive than echography of the kidneys for detecting ADPKD. The two diagnosis coincided in 50% of the cases. Comparison of the echographic and computer tomographic diagnoses in adults suspected of having ADPKD showed a high rate of coincidence (92.86%). Computer tomography is recommended for patients with inconclusive echographic findings for ADPKD. In such cases it can detect the disease in early childhood allowing efficacious follow-up and prophylaxis of complications. PMID- 8194805 TI - Surgical treatment of ruptured aneurysms of the abdominal aorta. AB - The number of patients suffering from aneurysms of the abdominal aorta (AAA) is rising simultaneously with the increase of the number of patients afflicted with cardiovascular disorders of atherosclerotic nature. Of the three very serious complications in such disorders-thrombosis, embolism, and rupture-the latter is the most serious and has a dramatic course. In the present study we discuss the surgical approach and the results of the treatment of 11 ruptured AAAs for the period from 1989 to 1991. Ten of the patients were male and one female. Their age was in the range of 51 to 87 (mean age 63.7 years). The diagnosis was primarily made on the basis of anamnestic and clinical evidence. Transvenous aortography was performed in four of the patients, and computer tomography was used in four other patients. Two patients were diagnosed in the operation theater placed there for an operation of acute abdomen. One of the patients was operated on only on the basis of the available clinical evidence because no other investigations were possible to have been performed. One patient died in the operation theater. One patient was operated on again in the early postoperative period because of the acute ischemia he developed in one of the lower limbs due to intraoperative embolic accident, and one patient was operated on later in the postoperative period because of two false aneurysms of the proximal and one of the distal anastomoses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194806 TI - Post-traumatic deep venous thromboses of the lower limbs. AB - The problem of the changes in blood coagulability and blood rheologic characteristics in traumatized patients is both old and topical. There are still many unresolved problems concerning the dynamics of the hemostasiologic status, the duration of immobilization and recovery of physical mobility, the anticoagulation treatment, the ways of reducing the possible complications, etc. In the present study the authors try to resolve some of these problems on the basis of their personal experience with 27 patients with soft-tissue traumas of the lower limbs complicated with deep venous thromboses. The role and place of the existent pathoanatomical changes in the region of the traumas as well as the dynamics of the pathophysiological mechanisms are discussed. The severity of the different complications and the measures for their prevention have also been considered. PMID- 8194807 TI - Effect of age-specific mortality on the average life expectancy in Bulgaria. AB - Using a concise method, we estimated the effect of mortality in specific age groups on the average life expectancy in Bulgaria. The method enables the calculation of the index from all causes of death as well as hypothetically, eliminating the mortality of the age groups involved in the study: under 1 year of age, 1 to 14-year-olds, 15 to 59-year-olds, and 60-year-olds and over 60. The detailed dynamic analysis of the influence of these four age groups mortality showed that the decrease in child mortality influenced positively the average life expectancy making it rise. This was especially clearly seen in the period until the mid-1960s. In the late 1960s the influence of the child mortality became insignificant and the major reserve for increasing the average life expectancy remained the decrease in active-life mortality. PMID- 8194808 TI - [The orthodontic classification of impacted canines with special reference to the age at treatment, the angulation and dynamic occlusion]. AB - The literature regards the surgical-orthodontic treatment of ectopic canine as being the optimal therapy. This treatment, however, often takes a long time and disturbances in the functional occlusion often occur after treatment is ended. For this reason it was decided to evaluate the treatment's success taking into consideration age at time of treatment, angulation, and functional occlusion. The post-treatment examinations of 66 patients up to five years after treatment reveal above all a correlation between treatment success and age at the time treatment begins. In addition patients with class II/2 and tooth aplasia were identified as constituting a risk group. These malocclusions, therefore, are a sign that there is a risk of ectopic canines. The occlusion type in laterotrusion movement provides group guidance. Beginning treatment after age 25 years should be critically evaluated, because the treatment period is prolonged. PMID- 8194809 TI - [Early deciduous tooth loss--the mature or immature eruption of their permanent successors]. AB - On the basis of 147 panoramic radiographs of 49 patients, this study investigated the influence of the premature loss of deciduous teeth on the formation of their permanent successors at the time of their eruption. Furthermore the study investigated the eruptive movement of the successor teeth at the time of eruption. In addition to detecting the accelerated emergence of still immature successor premolars, the study also determined that the extraction ot the deciduous molars before the age of eight years delayed the eruption of the permanent successors given the absence of an infected deciduous tooth with abscess formation. In relation to the eruptive movement of the permanent molars due to the premature loss of the second deciduous molar, the study ascertained a mesial movement of the first permanent molars and an accelerated eruption of the second permanent molars. PMID- 8194810 TI - [The etiology of hypodontia]. AB - Subject of our research were etiology and frequency of hypodontia and the possible effects of hypodontia on correct formation of dental arches in the course of dentition development. Methodologically the diagnostic records of 3238 patients of an orthodontic practice in Magdeburg, Germany, were evaluated. In addition to determining the frequency of hypodontia (8.1%), special attention was paid to accompanying micro-symptoms. 169 family members of 35 patients with teeth aplasia were questioned and examined and then extended family tables were drawn up. In addition, 105 dental casts from both patients with aplasia and patients with full dentition were measured. The results thus obtained made possible a comparison of the teeth and jaw size of the group with hypodontia with the group without hypodontia. PMID- 8194811 TI - [The diagnosis and treatment of congenital facial asymmetries in childhood. A clinical study]. AB - Following a brief discussion of etiology, pathogenesis, and diagnosis of congenital facial asymmetries, a new interdisciplinary treatment concept encompassing the disciplines of orthodontics, maxillo-facial surgery, and pedaudiology is set forth. This concept calls for the surgical reconstruction of the mandibular ramus and of the temporo-mandibular joint already in childhood in those cases in which functional jaw orthopedics has already begun at an early age. Thereafter the occlusal plane can be corrected orthodontically. Six patients were treated according to this concept. Two years nine months after surgery favorable results were observed in relation to occlusion and mandibular growth. Because, however, long term results are still outstanding, the results obtained until now and the treatment concept remain the subject of ongoing critical study. PMID- 8194812 TI - [Morphometric studies on the fetal development of the human mandible]. AB - Serial sections of eleven human mandibles of embryos and fetuses ranging in size from 18 mm CRL to 66 mm CRL were computer-graphically reconstructed. The extension of the Meckel cartilage and the mandibular bony structures were morphometrically studied. In emphasis the study encompassed measurements portraying length, width, dorsal opening angle, and the position of the mental foramen. In addition five mandibles of human embryos and fetuses with a size range between 30 and 50 mm CRL were radiographically examined. Results showed that in the younger specimens between 21 and 29 CRL size development of the structures of the mandible and the development of overall fetal body size take place independently from each other. During further development a change in the form of the mandible from a wide V over an acute V to a more rounded U form was observed. PMID- 8194813 TI - [A computer-controlled flexing test for determining the elastic parameters of highly flexible orthodontic wires]. AB - Metals are the most commonly used materials in the construction of orthodontic appliances designed for the correction of malocclusions. Knowledge of the force systems at work is a prerequisite for judging the functionality of these appliances. The elasticity parameters (Young's E-moduli, strain limits) of the alloys employed can be drawn upon to calculate numerically forces and torsional moments. Both tensile tests and bending experiments are used to determine the E moduli and strain limits of standard steel and highly flexible NiTi wires frequently used in orthodontics. However, parameters obtained by tensile tests are less suited for studying the mechanical properties of orthodontic appliances. Since bending deformation prevails, bending experiments should be preferred method for ascertaining the relevant parameters. This study, therefore, presents a new experimental method for testing the bend ability of highly flexible materials and the determination of the underlying material parameters. A comparison of calculated force systems with direct measurements revealed that bending parameters lead to an appropriate description of forces and moments generated during clinical treatment, whereas calculations based on tensile test parameters differ substantially. The bending test proposed here is, thus, a suitable means for dependably predicting the force systems produced by an orthodontic appliance and the test therefore can contribute to an accurate design of new types of therapeutic devices. PMID- 8194814 TI - [Gastroesophageal reflux. Pathophysiology, diagnosis and rational therapy]. AB - A combination of the typical symptoms heartburn and regurgitation may be considered virtual proof of gastroesophageal reflux disease. In the case of the atypical symptoms dysphagia, odynophagia, pharingitis, reflux-induced attacks of respiratory distress and intermittent chest pain further diagnostic investigation is indicated. Endoscopy reveals patchy reddening and possibly erosions, ulcers and strictures. Although the decisive pathophysiological factor in reflux disease is motility, the use in particular of acid suppressors represents an important part of treatment; in more severe reflux esophagitis (grades III and IV), proton pump inhibitors are the drugs of first choice. Gastro-esophageal reflux disease is a chronic condition with a recurrence rate of 60-80 percent. For prophylaxis, the minimum dose of antacids required to treat the stage must be administered. PMID- 8194815 TI - [Bouginage of peptic esophageal stenoses. Results of one year with long-term omeprazole medication]. AB - METHOD: Within the framework of an open prospective study, 47 patients with chronic reflux esophagitis, unresponsive to H2-receptor blockers and complicated by stenosis, underwent endoscopic bougienage. Unsuccessful treatment with H2 receptor blockers was followed in all patients by antisecretion treatment with omeprazole at a dose of 40 mg/day. RESULTS: At the latest after 3 months, stenotic and inflammatory changes had cleared up in all patients and under continued omeprazole over the long-term, remission of at least one year was achieved. CONCLUSION: A combination of endoscopic bougienage and simultaneous treatment with the proton pump blocker, omeprazole, represents effective treatment of chronic reflux disease complicated by stenosis. PMID- 8194816 TI - [Long-term results of bouginage of peptic esophageal strictures. A retrospective analysis of an 8 year time spain]. AB - BASIC REMARKS: Peptide stricture is a late stage of reflux esophagitis which prompts the patient to see a doctor for worsening dysphagia. METHOD: A retrospective analysis over an 8-year period, during which 53 patients with peptic esophageal stricture underwent bougienage and received aftercare. Twenty five of these patients were interviewed with the aid of a questionnaire. RESULTS: In more than 80% of the patients, dilatation, usually performed on an outpatient basis, led to satisfactory results, in particular in combination with long-term medical treatment. Although repeat bougienage sessions were necessary--after lengthy intervals--in about one-half of the patients, the intervals between sessions became longer (1.5 to 1 bougienage session per year). CONCLUSION: Currently, bougienage to a diameter of 2.0 cm, in combination with 20 to 40 mg omeprazole administered long-term, would appear to represent optimal treatment. PMID- 8194817 TI - [Current developments in antiviral chemotherapy. 1: Principles and overview- amantadine]. PMID- 8194818 TI - [Dimethylsulfoxide (DMSO) gel in treatment of acute tendopathies. A multicenter, placebo-controlled, randomized study]. AB - METHOD: In a placebo-controlled double-blind study, 157 patients with acute tenopathies (periarthropathia humeroscapularis or lateral epicondylitis) were randomized to treatment with either DMSO gel 10% applied three times a day (n = 77) or the gel excipient (n = 80). The treatment phase was 14 days long and included four examinations. Treatment was started within 72 hours after the onset of the acute symptoms. RESULTS: Pain of movement under loading and the mobility of the joints were significantly improved after, respectively, 3 and 7 days treatment with DMSO, as compared with placebo. After 14 days on DMSO, a further improvement was observed, and 44% of the patients were pain-free (placebo 9%). In both groups, the substance was well or very well tolerated by more than 90% of the patients. No relevant changes in laboratory results or severe undesired events occurred under treatment. Undesired events were seen in 8 patients receiving DMSO treatment, and in 3 patients in the placebo group. CONCLUSION: The results of this study confirm that Rheumabene (10% DMSO gel) is suitable for topical use in the treatment of acute tenopathy, producing clinically relevant results with little risk to the patient. PMID- 8194820 TI - [Suspected choledocholithiasis--diagnostic-therapeutic procedure]. PMID- 8194819 TI - [Strategies in rehabilitation after stroke]. AB - The rehabilitation of stroke patients should be initiated early on in the hospital admitting them, and then be continued in a specialist hospital or rehabilitation center, where applicable on an outpatient basis over the long term. Although the major improvements occur within the first 3 to 6 months, they may also occur beyond this period. Since, in the individual case, the results of treatment cannot be reliably predicted, every stroke patient should be sent for rehabilitation whenever possible. Treatment is oriented to the respective functional disorders, and is conducted by an interdisciplinary team headed by a physician. Even in cases with a severe residual deficiency syndrome, the chances of achieving at least partial independence with respect to daily activities, in particular walking, are favorable. The facilities for outpatient rehabilitation should be improved and self-aid groups, as also the training of relatives, promoted. PMID- 8194821 TI - [Treatment of keloids and hypertrophic scars. Pilot study with intralesional Lipotalon injections]. AB - A pilot study was conducted to establish whether intralesional injection of a microsomal corticoid, Lipotalon, would reduce the development of keloids and hypertrophic scars. Thirteen patients with 17 scars and keloids were admitted to the study. In all the patients investigated, injection of Lipotalon into the lesion led to a moderate to appreciable improvement in the hypertrophic scars and keloids. Injections of 0.5 to 4 mg Lipotalon were given, for the most part, at intervals of 4 to 6 weeks, and were oriented to the respective findings. No side effects were observed. Some of the patients received topical application of Lipotalon as adjuvant treatment to surgical scar resection. Here, too, a trend towards positive results was observed, although in one case, disordered wound healing was seen. PMID- 8194822 TI - [Reformulation regarding dementia. Alzheimer's disease--HIV dementia]. PMID- 8194823 TI - [Quality circles in family practice--roots, concepts, perspectives]. PMID- 8194824 TI - [Rehabilitation in coronary heart disease. Value, indications and contraindications of exercise therapy]. AB - In the rehabilitation of patients with coronary heart disease, physical therapy, in particular kinesitherapy plays a central role. The effects of regular endurance training are multifarious, ranging from improvements in functional capacity to a reduction in risk factors and to psychosocial aspects. At the beginning of the rehabilitation program in particular, safety and close supervision are of primary importance, and training on the bicycle ergometer is a first choice method. Depending upon the extent of the coronary heart disease, for example disordered functioning of the left ventricle or postoperative status following revascularisation surgery, modification and adaptation of the treatment regimen may be required. The risk of a cardiovascular incident occurring is low, and extensive studies performed in recent years have shown a reduction in cardiovascular mortality through the use of long-term rehabilitation programs. PMID- 8194825 TI - [Current status of preclinical therapy of myocardial infarct]. AB - The mortality associated with myocardial infarction can be considerably reduced by the use of thrombolysis, the success rate being determined largely by the time elapsing between attack and treatment. Despite various campaigns to inform the public, the time elapsing between symptom onset and alerting the doctor continues to be measured in hours. In view of the possible complications that may occur already during patient transport to the hospital, the emergency physician should be involved immediately. Basic treatment comprises the administration of oxygen, sedatives, analgesics and nitrates. Initiation of thrombolysis by the emergency physician is associated with a number of difficulties (uncertainty of diagnosis, equipment, experience). Since prehospital thrombolysis has not yet been shown to be of general advantage, it may be recommended only when transport is long and when the personnel and equipment requirements are met. The greatest benefit is to be expected from a shortening of the time lapse before alerting the doctor. PMID- 8194826 TI - [Treatment of patients with acquired (non-HIV) immune deficiencies]. AB - Infection continues to remain a major problem in immunodeficient patients. The spectrum of pathogens differs, depending on whether one is dealing with an unspecific immune defect or a specific hormonal or cellular defect. This means that a knowledge of the type of deficiency presenting is of importance for the empirical treatment that is often required. Infection can be prevented by the replacement of immunoglobulins, in particular in the case of hormonal immune defects. The use of cytokines holds out some promise of achieving a similar effect in the treatment of cellular immune defects. PMID- 8194827 TI - [Suspected kidney tumor--diagnostic-therapeutic procedure]. PMID- 8194828 TI - [Conversion of atrial fibrillation after mitral valve valvuloplasty]. AB - As in the case described here, thromboembolism originating in the heart may indicate stenosis of the mitral valve. In addition to the risk of an embolism, increased by factor 17 in the case of rheumatic mitral valve disease, such patients have hemodynamic problems, in particular resulting from the loss of active atrial contraction in atrial fibrillation. Surgical correction of a mitral stenosis can be delayed for years by balloon valvuloplasty. Following decompression achieved in this way, cardioversion to sinus rhythm may be worth attempting, even when the atria are clearly dilated. PMID- 8194829 TI - [Soon a fully automated HIV test will be ready for marketing]. PMID- 8194830 TI - [Names of famous physicians and their goals. On the founding of the Congress of Internal Medicine (1882) on the occasion of the 100th meeting]. PMID- 8194831 TI - Mitochondrial cardiomyopathy. AB - Accumulating evidence emphasizes the role of genetic factors in the development of cardiomyopathy. Mitochondrial cardiomyopathy is defined as cardiomyopathy caused by mitochondrial DNA mutations. The rate of mitochondrial DNA mutation is estimated to be much higher than that of nuclear DNA. It has been demonstrated that mutations of mitochondrial DNA are found in a variety of diseases, suggesting a new concept of mitochondrial disease. This contribution reviews the concept, molecular genetics, family history, pathology, clinical symptoms, diagnosis and therapy of mitochondrial cardiomyopathy. PMID- 8194832 TI - Deciphering the molecular genetics of congenital heart disease. AB - Congenital heart diseases are starting to benefit from the major advances provided by the advent of molecular biology methods. It is now possible to identify genes which are responsible for congenital heart diseases. The gene responsible for supravalvular aortic stenosis--an autosomal dominant trait--was cloned last year. It is the elastin gene. DiGeorge and Shprintzen syndromes, conotruncal anomaly face and some cardiac malformations have a common cause: a deletion of the 22q11 region resulting in a monosomy. Although the region of deletion is large, it is possible that monosomy of only one gene results in these conditions. Studies are underway to evaluate the impact of this new genetic factor on the incidence of congenital heart malformations. Studies on familial bundle branch block, and lateralization defect with midline anomalies are soon going to show a chromosomal region with the gene defect. Discovering the genes and their protein products which are implied in the cardiac morphogenesis will definitively change our understanding of these cardiac malformations. PMID- 8194833 TI - Clinical and genetical aspects of the long QT syndrome. AB - The idiopathic long QT syndrome (LQTS) is a congenital disorder characterized by a prolongation of the QT interval and by the occurrence of stress-induced syncope or cardiac arrest due to ventricular tachyarrhythmias. Such lethal events may be prevented by quite effective pharmacological or surgical antiadrenergic therapies. Two pathophysiological hypotheses have been considered: 1. A "sympathetic imbalance" caused by a lower than normal right sympathetic activity and 2. A cardiac cellular dysfunction, possibly an altered potassium channel. Although one may find clinical features of LQTS compatible with both hypotheses, there is no proof for either of them. Since a locus has been mapped for the long QT syndrome on the short arm of chromosome 11 in several families, tightly linked to the Harvey-ras-1 (H-ras-1) gene, this gene became a candidate gene for LQTS. It is an attractive hypothesis that an alteration in the H-ras-1 gene may cause LQTS by modulation of acetylcholine-activated potassium channels through guanine nucleotide-binding RAS proteins. No mutation in the H-ras-1 gene has been found until now, so that other genes located in this region close to H-ras-1 have to be considered to cause LQTS. Moreover, the variability of the clinical picture in patients with LQTS and the absence of linkage to the H-ras-1 locus in other families make genetic heterogeneity likely. Advances in recombinant DNA technology raise the possibility to identify the abnormal gene(s). This could be the basis to understand the pathogenetic of LQTS leading to a more accurate diagnosis and possibly new therapeutic concepts. PMID- 8194834 TI - Impact of molecular genetics in cardiac diseases. AB - Genetic linkage mapping has become an important technology applied to the study of human biology and in particular, for the delineation of the molecular basis of diseases through gene isolation and characterization of mutations in DNA. This approach was applied to cardiac hereditary disorders only a few years ago through the analysis of familial hypertrophic cardiomyopathy and congenital long QT syndrome. For both diseases, there is a striking genetic heterogeneity and analyses of genotype-phenotype correlations are underway. Familial occurrence is likely to play also an important role in idiopathic dilated cardiomyopathy. Genetic testing and risk stratification will be more complicated than it was initially expected, but hope is now there to discover new ways for preventing, diagnosing and treating deadly cardiac disorders. PMID- 8194835 TI - Myosin mutations in hypertrophic cardiomyopathy and functional implications. AB - Hypertrophic cardiomyopathy (HCM) can be an inherited disorder. Typically, the inheritance is dominant and genetic cases account for about 50% of all patients with this pathology. Four different HCM loci have been mapped to different chromosomes (no. 1, 11, 14 and 15), yet, only one responsible gene has been identified. It is the beta myosin heavy chain gene on chromosome 14, which is expressed in ventricles and in slow skeletal muscle fibers. A large number of missense mutations has been reported which are predominantly located in the globular head region of the beta myosin. An apparent hot spot of mutation has been detected within exon 13 of the gene, corresponding to amino acid position 403. Although the functional consequences of the various mutations for the activity of beta myosin are not known, by inference and on the basis of published data, it may be suggested that a mutation in position 403 affects the myosin actin dissociation in the contractile cycle. Despite our knowledge of mutations in the myosin gene, and of many of the pathological sequelas, there still is insufficient information which precludes unequivocal conclusions on the molecular mechanisms by which the pathogenesis of the myosin deficient heart develops. Molecular biology and genetics should help to define the determinants of this disease. PMID- 8194836 TI - Clinical and genetical heterogeneity of familial hypertrophic cardiomyopathy. AB - Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease which has a benign clinical course in most patients but carries also the risk of sudden cardiac death. Initial genetic studies have revealed the beta-myosin heavy chain (beta-MHC) gene on chromosome 14q11-q12 as morbid gene. Several mutations have been identified, almost all of them are missense mutations of the area in the gene coding for the globular head region of the myosin. The codon 403 has been found to be a hot-spot for mutations. Both, mutant myosin messenger RNA and proteins have been found in cardiac and in skeletal muscle, indicating the presence of a normal protein synthesis of the mutant allele. Histological studies show that gross alterations in protein assembly do not occur (e.g. by introducing the 403Arg-->Gln mutation in cell expression systems) and in-vitro motility of distinct mutations may be reduced in comparison to wild type myosin. The exact mechanism, however, how myosin mutations cause FHC has not yet been elucidated. Three novel loci for FHC have been identified only recently on chromosomes 1q3, 11p13-q13, and 15q22. It can be hoped that the characterization of the morbid genes in these loci will provide valuable information for the clarification of the pathogenesis of FHC and possibly for future therapeutic approaches. The challenge for future studies is to identify the morbid genes of the new loci, their mutations and their proteins. PMID- 8194837 TI - Clinical genetics of dilated cardiomyopathy. AB - The pathogenesis of dilated cardiomyopathy (DCM) remains controversial. Over the last few years there has been a gradual accumulation of evidence suggesting that familial forms of DCM are common and are most likely due to the transmission of a rare autosomal dominant gene. Despite these observations absolute proof that familial DCM is genetic is not available and there are many unanswered questions about the molecular basis of familial DCM. Is familial DCM caused by a single rare genetic defect or are there a number of genes involved which can be transmitted by different mechanisms? What factors govern whether an individual with an abnormal gene develops clinical DCM? Do individuals with mild echocardiographic abnormalities have early DCM? By performing linkage analysis on large informative families with familial DCM clinical cardiologists and geneticists should be able to address these and other important questions. Identification of the gene, or genes, responsible for familial DCM promises to permit reliable preclinical diagnosis to be made and enable unrecognised carriers of the condition to be identified. In addition to the impact this will have on genetic counselling and on our understanding the broader topic of pathogenesis, this will have important consequences for clinicians. Knowing a family member is genetically affected but preclinical will allow treatment to be started early in the natural history of the disease and new treatment strategies specifically against DCM to be developed. We are optimistic that the application of molecular biological techniques to the clinical genetics of DCM heralds the beginning of a new era in our understanding and treatment of this condition. PMID- 8194838 TI - Molecular genetics of dilated cardiomyopathy. AB - The recent advances in molecular biology and genetic engineering are producing relevant results in cardiology, in particular in the field of cardiomyopathies. Molecular genetics has been used for the detection of viral genomes persisting in myocardial tissue of patients with idiopathic dilated cardiomyopathy (IDC). Very recent data, based on highly sensitive and specific technologies, suggest, however, that enterovirus persistence is not a major cause of the disease. Another application of molecular genetics is the study of the familial form of IDC, using linkage analysis as a tool for the identification of the disease gene. According to this method, the X-linked form of familial IDC has been mapped within the dystrophin gene in a series of families, and preliminary reports suggest that the mutation (or mutations) concerns the muscle-promoter region. Linkage studies on the autosomal dominant form of IDC are in progress. A possible approach is the identification of linkage between the disease and an array of "candidate genes". Preliminary data have ruled out the involvement of a series of relevant candidates genes, among which the cardiac beta-myosin heavy chain gene. An alternative approach for linkage studies is to perform a random screening of the genome, in which a large number of anonymous markers are selected and tested. In conclusion, molecular genetics is starting to provide fundamental data about the pathogenetic mechanisms of IDC. The relevance of these findings is also crucial for clinical and therapeutic implications. PMID- 8194839 TI - Potential role for low dose limited-field radiation therapy (2 x 2 grays) in advanced low-grade non-Hodgkin's lymphomas. AB - The purpose of this retrospective study was to evaluate the efficacy of low-dose limited field radiation therapy (LDLRT) in low-grade non-Hodgkin's lymphoma (NHL) patients, in order to outline its possible role. The rationale of the analysis was as follows: (1) there is no clear dose-response relationship for radiation therapy (RT) in localized low-grade non-Hodgkin's lymphomas (LGNHL); (2) long term disease-free survival can be achieved in advanced LGNHL with low-dose (1.5-2 Gy) fractionated total body irradiation; (3) moreover, some of our previous LGNHL patients stopped their conventional planned RT course for convenience after 5 to 7.5 Gy and remained free from local progression in irradiated volumes for a long period of time. Patient selection criteria were the following: (1) patients with low-grade NHL (LGNHL); (2) patients who received no other form of therapy concomitantly with LDLRT until evaluation of the response; (3) patients who received a planned dose of 4 Gy in two fractions and over 3 days in a limited field. Out of 37 patients, 27 patients were fully evaluable. Twenty-two patients had stage III or IV disease. The median longevity of the disease was 73 months. Twenty-five patients had previously received chemotherapy (18 with anthracyclines). Nineteen patients had received one LDLRT course only. Eight patients responding to the first LDLRT had received at least one subsequent LDLRT course. After the first LDLRT course, an objective response in irradiated sites was observed in 24 of the 27 patients (89 per cent). Ten and 14 patients respectively demonstrated a complete response (CR) (37 per cent) and partial response (PR) (52 per cent). Freedom from progression in irradiated volumes for evaluable patients ranged from 4 to 35 months. Among the eight patients who received at least two LDLRT courses, a total of 20 different areas were irradiated, and 15 areas (75 per cent) showed a CR. Toxicity due to LDLRT was minimal. In conclusion, low-dose limited-field RT resulted in a high proportion of responses in LGNHL. The mechanisms explaining this radioresponsiveness are poorly understood. However, the efficacy of LDLRT could have several clinical applications in the general management of patients with advanced LGNHL. PMID- 8194840 TI - Prognosis in low grade non-Hodgkin's lymphoma: relevance of the number of sites involved, absolute lymphocyte count and serum immunoglobulin level. AB - Eighty-eight patients with low grade non-Hodgkin's lymphoma were followed for a median period of 63 months. Sixty-eight per cent of the group were centrocytic/centroblastic B cell lymphomas by the updated Kiel classification. Fifty-one (58 per cent) of the patients were stage IV by the Ann Arbor classification. In 18 of these patients the bone marrow was the only site of extranodal involvement. Univariate survival analysis showed that the sum of involved sites was more discriminatory than Ann Arbor stage. Analysis by site of involvement showed that the liver and other intraabdominal sites were associated with worse survival than involvement of peripheral lymph nodes. Bone marrow and spleen involvement were not significantly associated with short survival. Increasing age at presentation was strongly associated with shorter survival and was also inversely correlated with serum albumin. Both low absolute lymphocyte count (< 1.0 x 10(9)/l), low serum IgG level (< 10 g/l) and low total immunoglobulins on presentation were significantly associated with short survival. Multivariate analysis showed that age, serum albumin and number of involved sites gave the best survival prediction. The sum of involved sites, immunoglobulin level and absolute lymphocyte count may be useful objective markers of prognosis in low-grade non-Hodgkin's lymphoma. PMID- 8194841 TI - Current awareness in hematological oncology. PMID- 8194842 TI - Oligonucleotides in the treatment of leukemia. AB - The use of synthetic oligonucleotides directed towards specific genes in the therapy of leukemias has evolved rapidly over the past 5 years to early clinical trials. Undoubtedly, use of these compounds for systemic therapy and bone marrow 'purging' will escalate. Such trials will be models for the treatment of many other malignant diseases and, indeed, non-malignant diseases which may be expected to respond to eradication of a specific gene function. We are currently at the threshold of a new era of therapy which holds the promise of totally transforming clinical medicine in the next decade. PMID- 8194843 TI - Founder effect: assessment of variation in genetic contributions among founders. AB - We present a Monte Carlo method for determining the distribution of founders' genetic contributions to descendant cohorts. The simulation of genes through known pedigrees generates the probability distributions of contributed genes in recent cohorts of descendants, their means, and their variances. Genealogical data from three populations are analyzed: the Hutterite population of North America, the island population of Sottunga from the Aland archipelago, and the large Utah Mormon population. Two applications of the Monte Carlo method are presented. First we investigate the relative opportunity for founder effect in the three populations, which have dissimilar pedigree structures and dissimilar disease gene frequencies. Second, we measure the reproductive success of population founders in terms of the number of genes they contribute to a cohort some number of generations descendant and compare the effects of polygyny versus monogamy on reproductive success. The distribution of Hutterite founder contributions describes the context for a classic founder effect. Hutterite founders have a higher probability of leaving no genes in the population (72%) than Sottunga (48%) and Mormon (48%) founders. However, founder genes that survive among Hutterite descendants do so in larger numbers on average than founder genes in the other two populations. Greater variation among monogamous Hutterite founders compared with Mormon polygynous founders demonstrates that polygyny alone does not maximize the variance in reproductive success; other population characteristics are at least as important for determining variability among individuals in their genetic contributions to a gene pool. Our findings make it difficult to appreciate the reproductive advantage of polygyny in the Mormon population. Although the expected gene contributions and their variances were larger for polygynous founders compared with other Mormons, the main effect of polygyny was to increase the probability that any polygynist left a few genes among descendants. Furthermore, only 12% of the variation in the genetic contributions of Mormon founders is explained by their number of offspring. We conclude that shallow genealogical data (from one or a few generations) provide a poor measure of long-term reproductive success. PMID- 8194844 TI - Hereditary disorders in the French Canadian population of Quebec. I. In search of founders. AB - Twenty-eight hereditary disorders are known to cluster in at least one region of Quebec, 24 of them in regions east of Quebec City, including 20 in the northeastern part of the province. Genealogies were reconstructed to identify the probable origin of 21 of these 28 disorders present in the French Canadian population. The results showed that most of the disorders were brought to Nouvelle-France by settlers coming from France in the seventeenth century. Only 249 of the 8483 settlers in Nouvelle-France contributed, as common founders, to these genealogies. The contribution of the province of Perche was significantly higher than expected from its relative weight to the founding nucleus of the French Canadian population in 19 disorders. Furthermore, 34 of the 48 different common founders from Perche were found in more than one disorder. PMID- 8194846 TI - Obesity in Pima Indians: genetic segregation analyses of body mass index complicated by temporal increases in obesity. AB - During the past half-century the prevalence of obesity in developed countries has increased greatly. Such short-term changes in prevalence must be environmentally determined, but genes can mediate response to environmental change, for example, through variable gene penetrance and expression. Obesity differences between bith cohorts complicate the interpretation of phenotypic comparisons between generations that span periods of change. Genetic segregation analyses of the body mass index in 618 Pima Indian nuclear families (2 generations) identified recessive major gene inheritance, which is the same pattern of transmission that has been found in several other populations. However, within-birth-cohort analyses of siblings (one generation) uniformly supported codominant major gene inheritance with no polygenic heritability. For untransformed data transmission probabilities were Mendelian in the later-born cohort and in the combined sample of siblings. After transformation to remove skewness, transmission probabilities were Mendelian only in the earlier-born cohort (i.e., those siblings born before a period of marked temporal increase following World War II). A higher penetrance of codominant obesity susceptibility genes in the younger generation would result in some genetically obese individuals who have no affected parents, thus simulating recessive inheritance. Taken together, the results of these analyses suggest that the recessive pattern we identified in the Pima Indian nuclear families could be accounted for by temporal changes in penetrance of codominant obesity-predisposing genes. By implication, more modest temporal increases in white and black populations could in part account for the recessive pattern of inheritance described by several investigators. PMID- 8194845 TI - Hereditary disorders in the French Canadian population of Quebec. II. Contribution of Perche. AB - In our previous paper (De Braekeleer and Dao 1994) we showed that most of the hereditary disorders present in the French Canadian population of Canada cluster in eastern Quebec. Furthermore, the disorders probably were brought to Nouvelle France in the seventeenth century by migrants coming from Perche, France. Here, the analysis of several historical, social, and demographic factors shows that, rather than migrants coming from other French provinces, migrants from Perche came from a limited area and settled in eastern Quebec, preferentially on the north shore of the St. Lawrence River. They arrived earlier than the other migrants and had a larger descendance. However, only a limited number of migrants from Perche were found in the founding nucleus of the hereditary disorders. Further analysis shows that the social system had major consequences on migration, marriage, kin network, and family behavior. Therefore the presence and the high frequency of most of the hereditary disorders in the French Canadian population appear to be the result of founder effect and genetic drift. PMID- 8194847 TI - Anthropometric variation and population structure of the island of Pag, Croatia. AB - Anthropometric variation in the population of the island of Pag (eastern Adriatic, Croatia) was investigated by using data on 14 head and 24 body dimensions. The data were related to past and present migration patterns, geography, and linguistics. The analyses revealed heterogeneity among three population groups inhabiting geographically defined regions of the island and heterogeneity among the village populations. The congruence between anthropometric variation, migration history, geographic distances, and current linguistic features says much for the strength of the isolating factors on this ecologically uniform island, which have effected the genetic structure of the population. PMID- 8194848 TI - Genetic characterization of the Cayapa Indians of Ecuador and their genetic relationships to other Native American populations. AB - One-hundred sixty-four Cayapa Indians living in the Esmeraldas Province (northwest Ecuador) were studied for several erythrocyte genetic markers (ACP1, ADA, AK1, CA2, ESD, GLO1, G6PD, PGD, PGM1 subtyping and thermostability, PGM2, SODA, and HB). The Cayapa show allele frequencies typical of those of South American Indians. The absence of the CA2*2, G6PD*A, G6PD*A-, HBB*S, and HBB*C alleles and the low PGM1*1A and PGM1*2A and high PGM1*1B allele frequencies indicate that very little (no more than 2%), if any, genetic admixture has occurred with the black community living in the same area. Correspondence analysis was used to study the genetic relationships between the Cayapa and other linguistically defined Amerind populations and between the Amerinds and the other two native American groups, the Na-Dene and Eskimo-Aleut. The results of this analysis, obtained on the basis of some erythrocyte and serum markers and some blood group systems, show (1) the close affinity between the Cayapa and other South American populations, (2) the absence in the Amerind group of a clear-cut correspondence between linguistic classification and genetic relatedness, and (3) the evident distinctiveness of the Amerinds from other native American people. PMID- 8194849 TI - Sequence correction and reassignment of the TaqI polymorphic site in the human inter-gamma-globin gene region, an African-specific marker. AB - We report here that the assignment of nt 37504 in the human inter-gamma-globin gene region of the HUMHBB locus sequence as a C is incorrect and should be replaced by a T. Accordingly, the polymorphic TaqI site, originally described at position 37503 as an African-specific marker, is actually located at position 37992. A PCR-based assay for this anthropologically important genetic marker is described. PMID- 8194850 TI - PCR amplification of alleles at locus D17S5: detection of new and rare long length alleles by oligoprobing in a survey of Australian populations. AB - Alleles of the hypervariable human locus D17S5 were amplified by polymerase chain reaction (PCR) and categorized by length. Unlike other surveys of this locus, the products of amplification were authenticated by Southern analysis using an oligomeric probe directed to part of the 70-base-pair (bp) variable number of tandem repeat (VNTR) region. A small number of unusually long alleles were located. In a survey of 201 unrelated Caucasian individuals, 16 alleles (size range, 170-1430 bp) and 59 genotypes were observed (heterozygosity, 86.4%; discriminating power, 0.963). In a similar survey of 166 traditional Australian aboriginals, 18 alleles (size range, 170-1430 bp) and 46 genotypes were found (heterozygosity, 80.8%; discriminating power, 0.942). The allele frequencies differed significantly between these two ethnically distinct populations. Comparisons are made with other anthropologically diverse populations. PMID- 8194851 TI - Polymorphisms of complement component I and C1R subcomponent of C1 in nine aboriginal Taiwanese populations. AB - Complement component I (IF) and C1R subcomponent of C1 (C1R) types were determined by isoelectric focusing and subsequent immunoblotting techniques for 658 individuals from nine aboriginal Taiwanese populations. The frequency of the IF*A allele ranges from 0.075 (Bunun) to 0.430 (Saisiat), and a new variant allele IF*B2 was found to have polymorphic frequency in the Atayal. The frequency of the C1R*1 allele ranges from 0.410 (Yami) to 0.650 (Atayal), and the frequency of the C1R*2 allele ranges from 0.265 (Atayal) to 0.586 (Saisiat). The C1R*5 allele was found in five populations (Atayal, Bunun, Ami, Puyuma, Yami), and the C1R*9 allele was found in two populations (Tsou, Puyuma). The results indicate a remarkable degree of genetic variability among these populations. The variability may reflect long-term genetic and geographic isolation of each population. PMID- 8194852 TI - Activation of a distinct subpopulation of pulmonary macrophages following exposure to biological response modifiers. AB - A distinct subpopulation of tissue-associated pulmonary macrophages (TAPM) displayed tumoricidal activity towards syngeneic and xenogeneic targets following in vitro incubation with N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP). This subpopulation, as well as, the predominant population of freely lavagable alveolar macrophages destroyed allogeneic targets following a similar incubation with either 6-0-stearoyl MDP (S-MDP) or recombinant interferon-gamma (IFN-gamma). IFN-gamma-induced in vivo tumoricidal activation of both populations of pulmonary macrophage was most effective when delivered either intravenously or via osmotic minipump infusion and least effective when administered by direct intratracheal instillation. The separate populations also displayed in vivo activation in response to liposome-encapsulated i.v. administered S-MDP. Under comparable conditions, IFN-alpha was not nearly as effective. Metabolic activation of TAPM, assessed by the release of increased levels of superoxide free radicals during phagocytosis, occurred following 24 hr exposure to S-MDP or lipopolysaccharide. Incorporation of these agents into multilamellar vesicle liposomes further augmented the release of superoxide observed at 24 hrs. Our results collectively demonstrated that a subpopulation of lung macrophage, a tissue-associated pulmonary macrophage, may be activated to a tumoricidal state and to release pronounced levels of oxygen free radicals following either in vitro or in situ treatment with several biological response modifiers. PMID- 8194853 TI - Development of a neutralizing monoclonal antibody against rabbit IL-1 receptor antagonist and utilization for ELISA and measurement of masked IL-1 activity in biological materials. AB - We developed a monoclonal antibody with neutralizing activity against the rabbit IL-1 receptor antagonist (IL-1ra) and a sandwich ELISA for rabbit IL-1ra. Using this ELISA, we measured IL-1ra contents in inflammatory exudate cells and culture supernatants of LPS-stimulated macrophages. The production of IL-1ra occurred rapidly after the onset of inflammation in vivo and after stimulation of macrophages in vitro and was sustained for a long period. The time interval for detection of IL-1 activity overlapped with the above mentioned period of IL-1ra production. In the presence of this neutralizing monoclonal IgG, the effect of IL 1ra in these biological specimens was nil and heretofore unrecognized IL-1 activity in the samples was measurable; the rate of this increment in activity ranging between 1.5- and 4.8-fold. We conclude that underestimations of IL-1 activity have been made and previously reported results on IL-1 activities in many biological materials have to be re-examined. PMID- 8194854 TI - Production of IL2 and IL3 in syngeneic mixed lymphocyte reactions of BALB/c mice are elevated during a period of moderate dietary protein deficiency. AB - The mixed lymphocyte reaction (MLR) is a model of T cell responsiveness to antigenic peptides complexed with major histocompatibility (MHC) proteins on antigen presenting cells (APC). Since dietary protein deficiencies alter T cell development, syngeneic and allogeneic MLR were investigated in mice fed a low protein 4% casein (4Ca) or control 20% casein (20Ca) diet. Proliferation of splenic lymphocyte populations from BALB/c mice fed 4Ca was increased during syngeneic and allogeneic MLR compared with lymphocytes from mice fed 20Ca. Increased proliferation was accompanied by significantly higher production of IL2 and IL3 during syngeneic, but not allogeneic MLR. To determine the influence of autologous B cells on IL2 and IL3 production during MLR, lymphocyte populations of mice fed 4Ca or 20Ca were depleted of B cells. Splenic lymphocyte populations of mice fed 4Ca that were depleted of B cells did not exhibit increased IL2 or IL3 production during syngeneic or allogeneic MLR. Splenic APc of mice given 4Ca caused greater proliferation during MLR. However, APC of 4Ca mice did not cause greater IL2 or IL3 production. Similarly neither IgM-B cells nor macrophage from mice fed 4Ca induced elevated IL2 or IL3 production during syngeneic or allogeneic MLR. A dichotomy appeared in that 4Ca-APC were able to induce higher T cell proliferation but not cytokine production compared with 20Ca-APC. The enhancement of T cell responsiveness to Class II MHC determinants on APC during moderate protein deficiency appears to require both T and B cells from mice fed the deficient diet. PMID- 8194855 TI - Effect of Artocarpus integer lectin on functional activity of guinea-pig complement. AB - The effect of Artocarpus integer lectin (lectin C) on the functional activity of guinea-pig complement was investigated. Purified and crude extract of lectin C from six cultivars of Artocarpus integer seeds were found to consume complement and thus decreased the complement-induced haemolytic activity of sensitized sheep erythrocytes. The change in the complement-mediated haemolytic activity was significantly decreased when incubation of the lectins was performed in the presence of melibiose. The reversal effect of the carbohydrate, which is a potent inhibitor of the lectin's binding to O-linked oligosaccharides of glycoprotein, demonstrate involvement of the lectins interaction with O-glycans of glycoproteins in the consumption of guinea-pig complement. PMID- 8194856 TI - Induction of systemic immunologic hyporesponsiveness to ovalbumin in neonatal rats by the enteric administration of peptic fragments of ovalbumin. AB - The orogastric administration of protein antigens can induce specific systemic immunologic hyporesponsiveness to the antigens. Some evidence has suggested that fragmention of the antigens by proteolytic enzymes in the gastrointestinal tract is a necessary step in this phenomenon. We administered either ovalbumin (OVA) or fragments OVA, produced by digestion with pepsin, into the stomach or jejunum of suckling rats and measured the serum IgG antibody response to a subsequent intraperitoneal challenge with OVA. Whereas OVA administered by gastric gavage caused virtually a complete unresponsiveness to the OVA challenge, administration into the jejunum had no significant effect. Administration of peptic fragments of OVA (about 8000 Da) into either the jejunum or stomach caused systemic unresponsiveness in 62% and 67% of animals, respectively (p < .05 vs buffer-fed controls). Smaller fragments of OVA (< 2000 Da) given into the stomach or jejunum had no effect on systemic IgG responses, nor did administration of the 8000 Da fragments intraperitoneally. We conclude the 1) systemic immunologic tolerance to OVA can be induced by enteric administration of critical-size fragments of OVA, and 2) encounter of the OVA fragments, like intact OVA, via the gut yields a distinctly different response from that which follows parenteral administration. PMID- 8194857 TI - Production of type II collagen specific monoclonal antibodies. AB - Immunoassays are used for the specific measurement of type II collagen, a major cartilage protein, which is lost in osteoarthritic joints. Poor immunogenicity and species dependent immune response to type II collagen make it difficult to obtain specific antibodies required for immunoassay development. In addition, type II collagen antibodies exhibit reactivity to structurally dissimilar antigens such as actin, myoglobin, thyroglobulin and ssDNA, complicating the isolation of specific antibodies. It is therefore necessary to characterize the antibody reactivity against both noncollagenous antigens and different collagen types. In this study, immune response to type II collagen was improved by conjugation to carrier proteins, KLH and BSA. Hybridomas were generated by fusions of lymphocytes derived from lymph nodes or spleens with X63-653-Ag8 myeloma cells. Compared to spleens, the utilization of lymph nodes as a source of lymphocytes resulted in a 23% higher number of hybridomas secreting type II collagen antibodies. Hybridomas secreting polyreactive antibodies were identified based on their reactivity to thyroglobulin and eliminated. Extensive testing of the remaining monoclonal antibodies with other structurally dissimilar antigens and various types of collagen for reactivity, allowed us to isolate specific monoclonal antibodies to type II collagen. We emphasize the importance of characterization of the reactivity of type II collagen monoclonal antibodies before employing them for immunoassays. PMID- 8194858 TI - Modulatory effects of ceruloplasmin on lymphocytes, neutrophils and monocytes of patients with altered immune status. AB - We investigated the effect of plasma ceruloplasmin (Cp) on the different types of lymphocyte rosetting, and phagocytosis of polystyrene particles and culture Candida albicans by peripheral blood neutrophils and monocytes. Lymphocytes, neutrophils, and monocytes were isolated from the blood of patients with elevated immuno-status (n = 9), healthy donors (n = 21), and patients with reduced immuno status (n = 21). The ability of Cp to decrease the number of lymphocytes forming E- and EAC-rosettes and rosettes with auto-erythrocytes was shown for both patients and healthy donors. The maximal decrease of the number of E-rosettes (by 35%) and EAC-rosettes (by 57%) was shown for lymphocytes of the patients with elevated immuno-status. Cp had an effect on rosetting only when lymphocytes were preincubated with it, suggesting that Cp binding to lymphocytes was responsible for these effects. The decrease in all types of rosetting caused by Cp was dose related, with a maximum effect at physiological concentration of Cp (300 micrograms/ml). We demonstrated an enhancing effect of Cp on phagocytosis of Candida albicans and polystyrene particles by neutrophils (with a maximum enhancement by 180% for neutrophils of the patients with decreased immuno-status) and monocytes (with a maximum of 89% for monocytes of healthy donors). Cp enhances phagocytosis of neutrophils and monocytes by binding these cells, not by opsonizing ingested particles as a conventional opsonin (ie. lipopolysaccharide from E.coli). The stimulating effect of Cp on phagocytosis was three times higher than that of LPS from E.coli. PMID- 8194859 TI - Intracellular pH regulation in rat Schwann cells. AB - We examined H+ and HCO3- transport mechanisms that are involved in the regulation of intracellular pH of Schwann cells. Primary cultures of Schwann cells were prepared from the sciatic nerves of 1-3-day-old rats. pHi of single cells attached to cover slips was continuously monitored by measuring the absorbance spectra of the pH-sensitive dye dimethylcarboxyfluorescein incorporated intracellularly. The average pHi of neonatal Schwann cells bathed in HEPES mammalian solution was 7.17 +/- 0.02 (n = 32). In the nominal absence of HCO3-, pHi spontaneously recovered from an acute acid load induced by exposing the Schwann cells to 20 mM NH4+ (NH4+ prepulse). This pHi recovery from the acute acid load was totally inhibited in the absence of external Na+ or in the presence of 1 mM amiloride. In both cases, the pHi recovery was readily restored upon readdition of external Na+ or removal of amiloride. In the steady-state, addition of amiloride caused a small and slow decrease in pHi which was readily reversed upon removal of amiloride. In the presence of HCO3-, removal of external Cl- caused pHi to rapidly and reversibly increase by 0.23 +/- 0.03 (n = 15) and the initial rate of alkalinization was 20.6 +/- 2.7 x 10(-4) pH/sec. In the absence of external Na+, removal of bath Cl- still caused pHi to increase by 0.15 +/- 0.02 and the initial rate of pHi increase was not significantly altered. In the nominal absence of HCO3-, removal of bath Cl- caused pHi to increase very slightly (0.05 +/- 0.01) with an initial dpHi/dt of only 4.4 +/- 0.2 x 10(-4) pH/sec (n = 4). Addition of 100 microM DIDS did not inhibit the pHi increase caused by removal of bath Cl-. These data indicate that 1) Rat Schwann cells regulate their pHi via an Na-H exchange mechanism which is moderately active at steady-state pHi. 2) In the presence of HCO3-, there is a Na-independent Cl-HCO3 (base) exchanger which also contributes to regulation of intracellular pH in Schwann cells. PMID- 8194860 TI - Na+ channels of Muller (glial) cells isolated from retinae of various mammalian species including man. AB - Within the last few years, the expression of voltage-dependent, TTX-sensitive Na+ channels has been demonstrated in several types of neuroglial cells such as astrocytes and Schwann cells. Recently, we reported the occurrence of such Na+ currents in retinal Muller (glial) cells from dog and cat. This paper deals with the description of the properties of Na+ currents in Muller cells isolated from retinae of several mammalian species, as well as from human retinae. These Na+ currents were eliminated by TTX (1 microM), and by exposure to sodium-free extracellular solution; typically, they were demonstrable only after blocking most of the K+ conductance by Ba2+ (1 mM). Voltage-dependent activation and inactivation characteristics and time constants of the Na+ currents were similar to those of currents carried by neuronal Na+ channels. The estimated number of sodium channels per cell was low (about 1,500 channels per 7,500 microns 2), and the K+ conductance exceeded the peak Na+ conductance by an average factor of 5. Thus, the cells were incapable of generating action-potential-like responses under current clamp. Modelling estimations show that triggering of glial Na+ currents under physiological conditions, if any, can at best occur by emhaptic transmission at perinodal sites of optic axons. It is speculated that glial Na+ channels might be involved in neuroglial signalling events. PMID- 8194861 TI - Human angiotensinogen is highly expressed in astrocytes in human cortical grafts. AB - Human fetal parietal cortical tissue was transplanted to cortical cavities in immunosuppressed rats. Protoplasmic astrocytes in the human cortical grafts highly expressed human angiotensinogen mRNA as identified with 35S-labeled and digoxigenin-labeled riboprobes combined with immunohistochemistry for glial fibrillary acidic protein. Antibodies to human specific neurofilament protein 70 KD were used to characterize neurons in the graft and fiber outgrowth into the host brain. Immunohistochemistry revealed human angiotensinogen-like immunoreactivity in many small protoplasmic astrocytes and very few large neurons. These results demonstrate that human angiotensinogen mRNA and protein is synthesized in immature human glia. We assume that angiotensinogen is transformed into angiotensin peptides, which may participate in the regulation of growth processes. The results suggest that human angiotensinogen may play a role during human embryogenesis. PMID- 8194862 TI - Contact with myelin evokes a release of calcium from internal stores in neonatal rat oligodendrocytes in vitro. AB - The response of neonatal rat oligodendrocytes to contact with myelin extracts prepared from the central and peripheral nervous system was examined. Contact with either CNS myelin or PNS myelin resulted in collapse of the fine structure of the leading edge of oligodendrocytes in vitro. The collapse of the fine structure of oligodendrocyte processes was preceded by a substantial (approximately fivefold) increase in intracellular free calcium concentration. The calcium concentration increase was due, at least in part, to a release of calcium from internal stores, since it persisted when extracellular calcium was removed by chelation with EGTA. The increase in calcium concentration and the coincident morphological change suggest that oligodendrocytes might be able to recognize and react to specific molecules on the surface of other oligodendrocytes. PMID- 8194863 TI - Isolation and characterization of conditionally immortalized astrocyte cell lines derived from adult human spinal cord. AB - As an approach to develop both oligodendrocytic and astrocytic cell lines from adult human spinal cord, a cellular preparation of highly enriched oligodendrocytes and their precursors was infected with a replication-deficient retrovirus containing DNA sequences encoding the temperature-sensitive mutant of SV40 large T antigen. Six immortal cell lines were obtained. At both permissive (33 degrees C) and non-permissive (38.5 degrees C) temperatures, all cell lines were positive for vimentin, two demonstrated glial fibrillary acidic protein (GFAP) immunoreactivity, and none expressed oligodendrocyte or microglial markers. The 2 GFAP-positive cell lines [human spinal cord (HSC)2 and HSC6] were further characterized. Karyotype analysis revealed that both HSC2 and HSC6 cells showed gain of chromosomal material and structural chromosomal abnormalities. However, at non-permissive temperature both cell lines were indistinguishable from primary human astrocytes by a number of criteria. These properties included glutamine synthetase activity, Na(+)-dependent glutamate uptake, K+ flux, purine evoked Ca2+ mobilization and entry, and the ability to support neurite outgrowth from embryonic rat retinal explants. The HSC2 and HSC6 cell lines may prove to be valuable models for studying the physiological properties of adult human astrocytes. PMID- 8194864 TI - A new model for synovial joint lubrication. AB - A new approach to synovial joint lubrication is presented using Bingham fluid as lubricant between the approaching porous cartilagenous surfaces. It is presumed that the thickness of the core formed, due to thickly concentrated hyaluronic acid molecules, increases as the surfaces come closer. This is due to the withdrawal of the base fluid through the boosted lubrication mechanism, leading to the formation of lubricating gel. This gel ultimately acts as boundary lubricant which prevents cartilage-to-cartilage contacts very briefly during a gait cycle. For most of the gait cycle, fluid film lubrication persists, and this fluid supports greater loads which are due to the development of increased pressures as compared with viscous lubricants. Thus, normal joints possess an in built mechanism to support greater loads, at the load-bearing joints, with less friction and wear. PMID- 8194865 TI - Variogram methods for the analysis of bony trabecular shadows in plain radiographs. AB - Conventionally, trabecular morphology is described from thin sections on the basis of visual inspection and basic biometric parameters such as mean trabecular plate thickness, bone density, etc. In the clinical situation non-invasive studies of mineralised tissues may be undertaken using densitometric measurements. A little-explored non-invasive alternative is to study the organisation of shadows of trabeculae in plain radiographs. In radiographic images cancellous bone appears as a texture made up of the superimposed shadows of trabeculae from many planes. In this paper some early attempts to adapt modern image processing techniques to the analysis of trabecular architecture are reviewed. A new statistical technique based on variograms is applied to the investigation of anisotropy in trabecular radiographs and to changes in anisotropy with age. The results of regression analyses of variograms indicate that they can clearly demonstrate age-related changes in trabecular architecture and discriminate between the pattern of ageing in males and females. This approach shows promise as a useful research and investigative tool in a variety of contexts. PMID- 8194866 TI - Picture archiving and communication systems (PACS) for medical application. AB - The term 'Picture Archiving and Communication Systems' (PACS) applies to networks of digital image modalities, image workstations and mass image stores connected among each other by image data communication structures and controlled by appropriate image and data management. Predominantly, PACS are intended for application in the medical imaging domain, particularly in hospitals, where, by completely replacing the currently used films, they are supposed to lead to the 'filmless radiology'. The development of PACS is still one of the challenging tasks in the computer engineering field, because the giant amounts of digital image data produced in medical diagnostics require the introduction of novel architectures and technologies. This article describes the key components of PACS. Typical user environments are analysed and the requirements on the performance of the elements of a PACS are defined. The bottlenecks of current technologies are evaluated and examples of advanced approaches to PACS networks, archive modules and image workstations are given. PMID- 8194867 TI - The regulation of p53 function: Steiner Award Lecture. PMID- 8194868 TI - Flow-cytometric and quantitative histologic parameters as prognostic indicators for occult retroperitoneal disease in clinical-stage-I non-seminomatous testicular germ-cell tumors. AB - Our study was performed to clarify whether the combination of DNA flow-cytometric and quantitative histopathological parameters improves the prediction of occult metastatic disease in clinical stage-I non-seminomatous testicular germ-cell tumors (NSGCT). We used archival paraffin primary-tumor tissue of 67 clinical stage-I NSGCT patients who had undergone retroperitoneal lymph-node dissection (RPLND). According to the RPLND specimens, 24 patients were at pathological stage I and 43 at pathological stage II. Archival blocks were redissected for histological re-evaluation. In addition, 50 microns sections were prepared according to the Hedley technique in order to obtain nuclear suspensions which were processed for flow cytometry (FC). In univariate analysis, the percentage of embryonal carcinoma, the percentage of immature teratoma and vascular invasion were the most accurate predictive histopathological parameters. The percentage of aneuploid cells in S-phase was the best predictive FC parameter. In multivariate analysis, the percentage of embryonal carcinoma and the S-phase fraction of aneuploid cells were the only independent markers for occult metastatic disease. According to this statistical approach, 91.0% of pathological stage-I and stage II cases were correctly classified. Sensitivity was 95.3% and specificity was 83.3%. Using histopathological criteria alone, only 56.7% NSGCT patients were correctly classified. PMID- 8194869 TI - Prognostic factors in renal-cell carcinoma: immunohistochemical detection of p53 protein versus clinico-pathological parameters. AB - Immunoreactivity for p53 protein was assessed in 100 cases of primary renal-cell carcinoma (RCC). The results were correlated with clinical survival data (follow up 24 to 84 months; mean: 39 months) and with clinico-pathological parameters, including nuclear grade, tumour stage, cell type, tumour architecture and tumour diameter. In all, 32% of the tumours were p53-positive; there was no difference in survival between p53-positive and -negative cases. Similarly, p53 expression did not correlate with any of the clinico-pathological parameters mentioned. Nuclear grade (grade 1 + 2 vs. grade 3 + 4) had a striking impact on prognosis and so, to a lesser extent, did tumour stage and the occurrence of a spindle-cell component. The immunohistochemical detection of p53 in RCC is not of prognostic value. The estimation of nuclear grade, however is a major predictor of prognosis. PMID- 8194870 TI - Nutrients and gastric cancer risk. A population-based case-control study in Sweden. AB - A population-based case-control study of gastric cancer was conducted in areas with contrasting incidence rates in Sweden. Face-to-face interviews were carried out with 338 (74.1%) of all eligible cases and 679 (77.3%) of the selected controls. Consumption of selected nutrients during adolescence and 20 years prior to interview was estimated, together with life-time intake of vitamin supplements. Ascorbic acid and beta-carotene had an unequivocal protective effect, but alpha-tocopherol and nitrate were also negatively associated with gastric-cancer risk. In a multivariate analysis including all of these factors, only ascorbic acid remained a significant protective factor. The only macronutrient positively associated with the risk of gastric cancer was fat: intake 20 years prior to interview, but not during adolescence, was found to have a significant impact. Supplementation with vitamins almost halved the risk after adjustment for dietary intake of the corresponding vitamins. While the protective effect of vitamin C and beta-carotene could conceivably be ascribed to other agents in the diet, the strong negative association between supplementation with vitamin C and risk of gastric cancer supports the hypothesis of a protective role of this anti-oxidant. PMID- 8194871 TI - The induction of apoptosis is a common feature of the cytotoxic action of ether linked glycerophospholipids in human leukemic cells. AB - The ability of 2 recent ether-lipid derivatives, aza-phospholipids BN52205 and BN52211, to induce apoptosis in different leukemia cell lines was investigated using I-octadecyl-2-methyl-rac-glycero-3- phosphocholine (ET-18-OCH3) as a positive control. HL60, K562, Molt-4 and U937 cells were exposed for 24 hr to 20 microM of drug. The 2 aza-derivatives were as cytotoxic as ET-18-OCH3: BN52205 and BN52211 selectively induced apoptotic death in HL60, Molt-4 and U937 cells, but not in the K562-resistant cell line. Around 50% of DNA was fragmented in HL60 cells after exposure to the aza-derivatives, and 34% and 20% of DNA was fragmented in Molt-4 and U937 cells respectively. Similar results were obtained when cells were exposed to ET-18-OCH3. Our data confirm that ether lipids induce apoptosis in a variety of human leukemic cells, providing a possible explanation for their selectivity and mechanism of action. PMID- 8194872 TI - Biological-clinical significance of selective loss of HLA-class-I allelic product expression in squamous-cell carcinoma of the uterine cervix. AB - To determine possible correlations between the selective loss of HLA-class-I allelic forms on neoplastic cells and their biological-clinical characteristics, 89 squamous-cell carcinomas of the uterine cervix were evaluated immunohistochemically using monomorphic and polymorphic antibodies against HLA-A, -B, and -C molecules and analyzed clinico-pathologically. Four of the carcinomas exhibited a lack of detectable class-I heavy-chain expression associated with beta 2-microglobulin. In 19 of 42 HLA-A2-positive patients, tumor cells revealed loss of the HLA-A2 allelic product. Loss of HLA-B7 and/or 40 (B7/40) allelic product(s) on tumor cells was observed in 12 of 25 HLA-B7/40-positive cases. These alterations did not correlate with patient age, clinical stage (FIGO) of the disease, histological sub-type (WHO) or depth of cervical invasion. However, a statistically significant correlation was observed between lymph-node metastases and selective loss of HLA-B7/40 allelic product(s), but not with HLA A2 allelic product on cancer cells of the primary lesion. Our results indicate that selective loss of certain HLA-class-I alleles on neoplastic cells can influence the nodal metastatic potential and suggest that these 2 class-I molecules may have different immune functions as restriction elements in T-cell mediated cytotoxicity. PMID- 8194873 TI - Early endothelium activation and polymorphonuclear cell invasion precede specific necrosis of human melanoma and sarcoma treated by intravascular high-dose tumour necrosis factor alpha (rTNF alpha). AB - Twenty-seven patients treated with high-dose rTNF alpha, IFN gamma and melphalan by isolated limb perfusion were histologically documented. There were 20 cases of melanoma-in-transit metastases and 7 cases of high-grade soft-tissue sarcoma. Biopsies were taken before IFN gamma, after IFN gamma, before TNF alpha and between 2 hr and 60 days after the TNF alpha perfusion. Immunohistochemistry was performed for adhesion molecules ICAM-I, ELAM-I (E selectin), VCAM-I and PECAM. During the first hours after beginning perfusion, the endothelial cells of the tumour capillaries appeared swollen. Significant tumour necrosis was already observed 3 hours after the perfusion in melanoma cases. The overall predominant feature was coagulative necrosis associated or not with haemorrhagic necrosis. TNF alpha induced increased expression of ELAM-I and VCAM-I adhesion molecules on intratumoral endothelial cells. The activated tumour vessels were progressively destroyed. Significant intravascular recruitment of polymorphonuclear cells (PMNs) was observed 3 hr after starting TNF alpha; it was followed by diapedesis and tumour colonization 3 days later. T lymphocytes and macrophages were detected during the first 7 days and B lymphocytes during the second week. Melanoma in transit metastases treated with alkylating agent alone did not show significant necrosis and did not express high levels of adhesion molecules (ELAM-I, VCAM-I) nor infiltration by PMN. PMID- 8194874 TI - Deletion mapping of chromosome 19 in human gliomas. AB - There is evidence that a putative glioma tumor suppressor locus resides on the long arm of chromosome 19. We present data on 161 gliomas from 156 patients, which were studied by microsatellite analysis for loss of heterozygosity (LOH) on chromosome 19. Eight loci on the long arm and 2 loci on the short arm of chromosome 19 were examined. LOH on 19q was observed in 3/19 astrocytomas (WHO grade II), 12/27 anaplastic astrocytomas (WHO grade III), 16/76 cases of glioblastoma multiforme WHO (grade IV), 4/9 oligodendrogliomas (WHO grade II), 3/5 anaplastic oligodendrogliomas (WHO grade III), 5/9 mixed oligo-astrocytomas (WHO grade II) and 8/10 anaplastic oligo-astrocytomas (WHO grade III). While 31 of the tumors with LOH on chromosomal arm 19q exhibited allelic loss at every informative locus, 20 tumors showed terminal or interstitial deletions. In contrast to astrocytomas and glioblastomas, tumors with an oligodendroglial component had predominantly lost the entire long arm of chromosome 19. The common region of overlap in gliomas was located on 19q13.2-q13.4 between the markers D19S178 and D19S180. Our data confirm the involvement of a putative tumor suppressor gene on chromosomal arm 19q in gliomas and assign this gene to 19q13.2 q13.4. PMID- 8194875 TI - Incidence of breast cancer in women with fibroadenoma. AB - There is a general agreement that fibroadenoma is associated with a certain increase in breast cancer risk, but the risk estimates appear heterogeneous according to various studies. To provide further quantitative and population based estimates of breast cancer risk in women with histologically confirmed fibroadenomas, we linked data of 1,461 incident cases of fibroadenoma (median age, 37 years) to the Cancer Registry of the Swiss Canton of Vaud (about 600,000 inhabitants) over the period 1977-1991. After exclusion of 57 synchronous breast neoplasms, a total of 17 cases of breast cancer were observed vs. 10.9 expected (standardised incidence ratio, SIR, 1.6; 90% confidence interval: 1.1-2.1). The SIR was similar in the short term (3-5 years) and in the medium-long term (> 5 years) following diagnosis of fibroadenoma. The cumulative risk of invasive breast cancer was 0.7% after 5 years and 2.2% after 12 years following diagnosis of fibroadenoma. This is not negligible on account of the young age of our cohort. PMID- 8194876 TI - Expression of Ca(2+)-binding proteins of the S100 family in malignant human breast-cancer cell lines and biopsy samples. AB - In order to examine whether the expression of calcium-binding proteins of the S100 family may correlate with the transformation grade of human mammary-tumor cells, we studied the expression patterns of 4 members of this family (CACY, CAPL, S100L, S100 alpha/beta) in human breast-cancer cell lines. Each S100 protein is shown to be individually regulated in the human breast-cancer cell lines we studied, but it appears that the expression levels of S100 proteins do not strictly correlate with prognostic factors or the tumorigenicity of the cells. However, 2 aggressive cell lines, MDA-MB-231 and HS-578T, show elevated expression of CAPL. We show that methylation may account for partial regulation of the S100 genes, whereas neither genomic rearrangements in the S100 gene cluster region nor gene dosis effects seem to influence their expression pattern in MDA-MB-231 and MCF-7 cells. On the basis of our genomic analyses, we can localize the gene for S100L within 5 kb upstream of S100E, thus extending the S100 gene cluster by one gene. A series of primary breast tumors was collected and tested for expression of CAPL, CACY and S100 alpha/beta. The results show that all human breast-cancer tissues tested express CACY, whereas the presence of CAPL is more restricted. There is a significant correlation between enhanced expression of CAPL and presence of the invasivity marker urokinase-type plasminogen activator (uPA). This observation suggests that CAPL may play an important role in the acquisition of metastatic potential of human mammary epithelial cells. PMID- 8194877 TI - Identification and potential use of a soluble tumor antigen for the detection of liver-fluke-associated cholangiocarcinoma induced in a hamster model. AB - A liver-fluke-associated cholangiocarcinoma (CCA), comparable to that occurring in humans, was induced by exposing Opisthorchis viverrini-infected hamsters to dimethylnitrosamine (DMN). Tumor masses were removed and histopathologically identified, then one portion was extracted for antigens used in the production of monoclonal antibodies (MAbs). The remaining portions were used to establish CCA cell lines. The antigens produced and secreted by these cell lines, as well as those originally present in the tissue extracts, possessed a 200-kDa glycoprotein that appeared to be immunologically distinct from other tumor markers. A specific MAb called 6E5 was used to set up a sandwich ELISA for the quantification of this antigen in the serum and bile of tumor-bearing animals. The assay system was sensitive enough to detect the antigen at concentrations below 10 ng/ml. The serum and biliary levels of this antigen were markedly elevated in animals with progressive tumors when compared with untreated controls. The serum taken serially from each animal that subsequently developed CCA showed a gradual but significant elevation of the antigen as carcinogenesis progressed. A few isolated animals exhibited a slight elevation of the antigen at a time as early as the end of DMN treatment, when the CCA should not yet have developed, judging from microscopic examination. The data from this animal model suggested that the CCA associated soluble antigen defined by MAb 6E5 was a useful marker for the detection of tumors at an early stage of development. PMID- 8194878 TI - Tumor-derived transforming growth factor-beta 1 and interleukin-6 are chemotactic for lymphokine-activated killer cells. AB - Adherent lymphokine-activated killer (A-LAK) cells are purified IL-2 activated natural killer (NK) cells with potent anti-tumor cytotoxic activity. They have been used in the adoptive immunotherapy of metastatic cancers. However, it has been shown that intravenously transferred LAK cells have a poor homing capacity to tumor sites. For the present study, the effects of tumor-derived factors on the in vitro migratory capacity of A-LAK cells was investigated. In a micropore migration assay the conditioned medium from 3LL Lewis lung carcinoma cell cultures was found to exert a strong chemotactic, but not chemokinetic effect on A-LAK cells. This effect was partially inhibited by neutralizing antibodies against the cytokines TGF-beta 1 and IL-6. A combination of the 2 antibodies completely suppressed the chemotactic activity of tumor-cell-conditioned medium. Purified TGF-beta 1 and recombinant IL-6 were chemotactic for A-LAK cells. Biological activities of both cytokines were detectable in the tumor-cell conditioned medium. The in vivo relevance of these findings, with respect to tissue infiltration of NK cells and LAK cells in inflammation or cancer, remains to be elucidated. PMID- 8194879 TI - Anti-tumor effect of combined treatment with thymosin alpha 1 and interleukin-2 after 5-fluorouracil in liver metastases from colorectal cancer in rats. AB - We studied the effect of combined chemo-immunotherapy, 5-FU followed by thymosin alpha 1 (T alpha 1) and interleukin-2 (IL-2) at low doses, on liver metastases from colorectal cancer, induced by splenic injection of DHD/K12 cells (1,2 dimethylhydrazine-induced colon adenocarcinoma) in syngeneic BDIX rats. The presence of liver metastases was checked by laparotomy 14 days after tumor-cell injection. Evaluable rats were assigned randomly to 5 experimental groups designated as control, 5-FU, IL-2, 5-FU/IL-2 and 5-FU/T alpha 1/IL-2. 5-FU was administered i.v. as a continuous infusion for 7 days by an osmotic device implanted surgically. T alpha 1 and IL-2 were administered for 4 days and repeated after 11 days. Combined chemo-immunotherapy was shown both to significantly reduce the growth of liver metastases and to prevent extra-hepatic spread. 5-FU/T alpha 1/IL-2 also improved survival rate. Combined immunotherapy after 5-FU restored NK activity of the peripheral-blood-mononuclear-cell (PBMC) in tumor and/or 5-FU immunodepressed rats and enhanced PBMC cytotoxic activity against the DHD/K12 autologous cell line. This model was devised to mimic the clinical situation of unresectable liver metastases. PMID- 8194880 TI - Scatter factor modulates the metastatic phenotype of the EMT6 mouse mammary tumor. AB - EMT6 is a transplantable mouse mammary tumor cell line that has been utilized widely as a model system to study the effects of various treatments on local tumor growth and pulmonary metastasis. In this study, we examined the cellular mechanisms by which scatter factor (SF), a fibroblast-derived cytokine that stimulates epithelial cell motility, may contribute to tumor-cell dissemination, using the EMT6 model system. In vitro, SF stimulated EMT6 cell motility, invasiveness and cell-surface expression of urokinase (an enzyme required for cell migration through tissue). SF differentially stimulated EMT6 cell adhesion to and migration onto surfaces coated with collagen I and laminin. EMT6 cells treated in vitro with SF and injected i.v. into isogeneic BALB/c-Rw mice showed a small but significant increase (1.7-fold) in lung colony formation as compared with control cells. For EMT6 cells in vitro, SF had no effect on DNA synthesis, cell proliferation, cell size distribution, or in vitro colony-forming ability. Thus, the increase in lung colonization may be due to enhanced ability of SF treated cells to adhere to subendothelial basement membrane or to invade through tissue. Studies of the tissue distribution of SF in BALB/c-Rw mice demonstrated high levels of active factor in the lung. Thus, the presence of endogenous pulmonary SF may have reduced the degree to which SF treatment stimulated EMT6 lung colonization. Significant SF activity was also found in extracts of EMT6 tumors. Cultured EMT6 cells did not produce SF, but did produce high titers of a soluble low-molecular-weight protein activity that is capable of stimulating SF production in human fibroblasts 3- to 5-fold. EMT6 tumor extracts contained high titers of a similar SF-inducing activity. These observations suggest that SF may contribute to the invasive and metastatic phenotype of EMT6 cells via a paracrine mechanism in which tumor cells induce the production of SF in stromal fibroblasts. PMID- 8194881 TI - Mitogenic activity of procathepsin D purified from conditioned medium of breast cancer cells by affinity chromatography on pepstatinyl agarose. AB - A simple procedure for the affinity purification of procathepsin D from tissue culture medium conditioned by breast-cancer cells is described. This procedure yielded 2 micrograms of procathepsin D/100 ml medium. The procathepsin D was approximately 95% pure as judged by silver staining of polyacrylamide gels, the major contaminant being mature cathepsin D. The ability of procathepsin D to stimulate the proliferation of oestrogen-responsive MCF-7 breast cancer cells was determined. The purified procathepsin D had no mitogenic effect alone or in combination with oestradiol or other growth factors. These data suggest that procathepsin D does not act as an oestrogen-regulated autocrine growth factor for malignant breast epithelial calls. PMID- 8194882 TI - Inhibition of metastasis of Lewis lung carcinoma by a synthetic peptide within growth factor-like domain of urokinase in the experimental and spontaneous metastasis model. AB - Four synthetic peptides (residues 20-30 and 17-34) within the growth factor-like domain (GFD) of murine and human urokinase-type plasminogen activator (uPA) were examined to determine whether they inhibit production of experimental and spontaneous lung metastasis by murine Lewis lung carcinoma (3LL) cells. In an in vivo experimental metastasis assay, which determines mainly the later steps of the metastatic migration process (extravasation from the bloodstream and then growth into pulmonary tumor), none of the peptides introduced by i.v. single co injection into syngeneic C57B1/6 mice inhibited pulmonary metastasis, when 3LL cells were pre-incubated with the peptides followed by i.v. co-injection of the peptide and cells. In addition, none of the peptides, when injected i.p. daily for 7 days after i.v. tumor cell inoculation, reduced the number of lung tumor colonies. In a second in vivo assay that measures metastasis from a primary tumor (spontaneous metastasis model), multiple i.p. injections of the mouse peptide 17 34 for 7 days after s.c. tumor cell inoculation significantly inhibited metastatic lung tumor colonization in a dose-dependent manner, whereas human peptide 17-34 had no effect. Mouse and human peptide 20-30 had no effect either. The inhibition of lung metastasis was not due to direct antitumor effects of mouse peptide 17-34. Our results indicate that occupation of uPA receptors on 3LL cells by the enzymatically inactive mouse peptide 17-34 or prevention of rebinding of uPA synthesized by tumor cells to their receptor specifically reduced tumor cell invasion and formation of metastasis and that uPA may regulate more efficiently the mechanism involved in the entry of tumor cells into vascular circulation than extravasation during the metastatic process. PMID- 8194883 TI - Characterization of a bombesin/gastrin-releasing peptide receptor on a human gastric-cancer cell line. AB - This study examined the expression of receptors of the bombesin (BBS) family in human gastric-cancer cell lines. Of 5 cell lines screened, only one, St42, demonstrated specific binding sites for 125I-Tyr4-BBS, which have been further characterized. This binding was saturable, and temperature- and time-dependent. Scatchard analysis of displacement data performed at 37 degrees C revealed 2 binding sites: a high-affinity, low-capacity site (KD = 0.13 nM, Bmax = 1500 sites/cell) and a lower-affinity, higher-capacity site (KD = 11 nM, Bmax = 35,000 sites/cell); the latter was lost when internalization of peptide was prevented, suggesting that it may be an artefact. Displacement assays with gastrin-releasing peptide (GRP) and neuromedin B (NMB) revealed that the receptor was of the GRP preferring sub-type (GRP IC50 = 0.35 nM; NMB IC50 = 112 nM). Co-valent cross linking of 125I-Tyr4-BBS to the receptor demonstrated the presence of a single band corresponding to a molecular weight of 37 to 44 kDa on SDS-PAGE, similar to that of the cloned GRP receptor protein core. G-protein linkage of this receptor was demonstrated by selective inhibition of 125I-Tyr4-BBS binding by guanosine nucleotides. The binding of BBS to the receptor resulted in a rise in intracellular calcium. Three of four structurally distinct BBS antagonists bound to the receptor with high affinity, but [DPhe12, Leu14]-bombesin did not cause any displacement of 125I-Tyr4-BBS even at 10 mM. The functional significance of GRP receptors on human gastric-cancer cells is as yet unknown, but further studies may determine whether such receptors have importance in the therapy of gastric cancer. PMID- 8194884 TI - Regulation of fibronectin and laminin receptor expression, fibronectin and laminin secretion in human colon cancer cells by transforming growth factor-beta 1. AB - Transforming growth factor (TGF)-beta 1 modulates the expression of extracellular matrix (ECM) glycoproteins, fibronectin and laminin and the adhesion of Moser colon cancer cells to these glycoproteins. Since adhesion can be altered through expression of cell-surface receptors, binding affinities of adhesion molecules for receptors, or both, we investigated the effect of TGF-beta 1 on the binding properties of fibronectin and laminin to their cell-surface receptors by saturation binding and Scatchard analyses using radiolabeled fibronectin and laminin. Fibronectin bound to its cell-surface receptor with high affinity (Kd = 1.25 x 10(-9) M), Moser cells had approximately 7.1 x 10(4) fibronectin-binding sites per cell. TGF-beta 1 treatment rapidly up-modulated the number of cell surface fibronectin-binding sites by 1.9-fold. The binding affinity of fibronectin for the receptor, however, was not altered. Laminin was found to bind to a higher-affinity and a lower-affinity receptor. Moser cells expressed approximately 1.1 x 10(3) higher-affinity laminin-binding sites and approximately 3.1 x 10(4) lower-affinity-binding sites per cell. TGF-beta 1 rapidly increased the expression of the higher-affinity sites 3-fold and the lower-affinity sites 5 fold. The binding affinity of both the higher-affinity and lower-affinity laminin receptors increased 3-fold after 2 and 6 hr of TGF-beta 1 treatment respectively. Concurrent with receptor modulation, TGF-beta 1 induced the secretion of fibronectin and laminin from Moser cells. Northern hybridization analyses showed a concurrent stimulation of the expression of the mRNAs for ligands (fibronectin and laminin) and the mRNAs for the integrin species of the fibronectin and laminin receptors (alpha 5 and alpha 6 subunits). Thus the production of fibronectin and laminin and the expression of their receptors were tightly co regulated by TGF-beta 1. PMID- 8194885 TI - HTLV-I messenger RNA is expressed in vivo in adult T-cell leukemia/lymphoma patients: an in situ hybridization study. AB - Adult T-cell leukemia/lymphoma (ATLL) is a malignancy involving peripheral blood, lymph nodes, skin and other organs. Human T-cell leukemia virus type I (HTLV-I) is etiologically associated with ATLL but cannot be detected by conventional methods in fresh samples of peripheral blood and skin taken from ATLL. The aim of this study was to investigate the feasibility of an in situ hybridization technique for detection of HTLV-I mRNA in atypical lymphoid cells of peripheral blood and skin lesions of patients with ATLL. We detected variable amounts of HTLV-I tax mRNA in the nuclei and cytoplasm of these cells in fresh peripheral blood samples and skin lesions from ATLL patients, and also in asymptomatic HTLV I infected donors to a lesser extent. Out of 10 patients with ATLL, 7 showed strong positive in situ hybridization whereas the other 3 were only weakly positive. However, in the last 3 cases, the reaction became strongly positive after cells had been cultured for 24 hr. Furthermore, all 3 asymptomatic HTLV-I infected donors exhibited a weakly positive response in their apparently mature lymphoid cells. PMID- 8194886 TI - Trends in childhood cancer mortality in the ex-USSR, 1965-1990. PMID- 8194887 TI - Immunotherapy with antibodies to the EGF receptor. AB - A series of rat monoclonal antibodies (MAbs) has been generated against the extracellular domain of the receptor for EGF which block the binding of EGF and TGF alpha to the receptor and inhibit the growth in vitro of a range of carcinoma cell lines that over-express the receptor for EGF. Some of these antibodies were able also to induce the complete regression of xenografts of EGFR-over-expressing tumours when treatment was started, either at the time of tumour inoculation or later when the tumours were established. The most effective of these antibodies was ICR62, which was also able to activate host immune effector functions. We conclude that antibodies which block growth-factor-ligand interaction can have a profound influence on the proliferative capacity of tumour cells in vivo and may have useful clinical application. PMID- 8194888 TI - Laminin receptor expression and function in small-cell lung carcinoma. AB - Interactions between tumor cells and laminin or other components of the extracellular matrix are thought to play a role in tumor invasion and metastasis. To analyze these interactions, we examined the expression of 5 types of laminin receptors on 11 cell lines derived from the highly malignant and metastatic tumor small-cell lung cancer (SCLC). The integrins VLA-1, VLA-3, VLA-6 and the 67 KDa monomeric receptor were expressed at various levels, whereas the VLA-2 receptor was absent on the cell lines. Only one cell line expressed none of these laminin receptors. All cell lines co-expressed alpha 6 beta 1 (VLA-6) and the 67-kDa molecule, the only receptors specific for laminin. Analysis of the ability of SCLC cells to bind radiolabeled laminin and to adhere to laminin substrata revealed a correlation between these 2 parameters and the expression of VLA-6 and the 67-kDa monomeric receptor. Cell adhesion was mediated by alpha 6 beta 1, as indicated by inhibition of adhesion using an anti-VLA-6 monoclonal antibody (MAb). Both VLA-6 and the monomeric receptor were up-regulated in vitro by laminin. PMID- 8194889 TI - L3p40-50--a new lung-tumor-associated 40- to 50-kDa antigen defined by a monoclonal antibody (L3). AB - A monoclonal antibody (MAb), designated L3, was raised against a human-lung adenocarcinoma-derived cell line, A549. Immunohistological studies showed reactivity of MAb L3 with 70 to 90% of lung tumors representing the 4 major histotypes. Strongest reactivity was seen with squamous-cell cancer and adenocarcinoma, with strong intracellular staining of the tumor cells. In small cell lung cancer, staining was seen in a minority of tumor cells. Normal tissue staining was seen with thyroid follicular cells and focally with epithelial cells of the bronchi, the colon and the small intestine. Normal liver parenchyma was negative, whereas hepatocytes surrounding metastatic lesions were strongly stained. This pattern of staining was also seen for connective tissue. Western blot analysis showed that the antigen defined by MAb L3 has an apparent molecular weight of 40 to 50 kDa, and hence is denominated L3p40-50. Our results suggest that L3p40-50 represents an undescribed tumor antigen. PMID- 8194890 TI - Re-assessment of acidic glycosphingolipids in small-cell-lung-cancer tissues and cell lines. AB - The occurrence of tumor-associated glycosphingolipids (GSLs) has been documented in a variety of cancer tissues (Hakomori, 1984, 1985, 1989). In the case of small cell lung cancer (SCLC), the monosialoganglioside IV2Fuc-II3NeuAc-Gg4Cer (Fuc GM1; short notations of gangliosides are according to Svennerholm, 1963), first described from bovine liver (Wiegandt, 1973), was found to be a unique tumor associated GSL (Nilsson et al., 1984). It is present in up to 90% of all SCLC cases as compared with 25% frequency in non-SCLC, and no occurrence in normal lung (Brezicka et al., 1989, 1992). Thus, Fuc-GM1 may represent a suitable target antigen for immunotherapy of SCLC, and successful experiments have been performed showing tumor-cell killing by monoclonal antibodies (MAbs) against Fuc-GM1, both in vitro and, in a mouse model, in vivo (Brezicka et al., 1991). However, an effective tumor vaccination in humans would require this antigen to be expressed by the primary tumor and also by all metastases. The co-expression of Fuc-GM1 has already been reported in primary tumors and in most but not all metastases of SCLC (Hanquing et al., 1986; Nilsson et al., 1986; Brezicka et al., 1989). In view of the significance this ganglioside may have for possible immunotherapeutical approaches to SCLC and of the difficulty in obtaining a sufficient number of samples for analysis, a re-assessment of Fuc-GM1 expression was made in SCLC primary tumors and their metastases, as well as in established SCLC cell lines. In addition, the possible presence of such gangliosides, that might help to explain the selective tetanus-toxin binding of SCLC cells (Critchley et al., 1986; Heymanns et al., 1989) was investigated. Finally, the typical occurrence of sulfatide in all SCLC tissues and cell lines could be established. PMID- 8194891 TI - Phenotypic differences among morphologically similar small-cell carcinomas detected with a panel of monoclonal antibodies and indirect immunofluorescence and flow cytometry. AB - Indirect immunofluorescence and flow cytometry were used to determine reactivity of a panel of 75 monoclonal antibodies (MAbs) and controls (provided by the Third International IASLC Workshop on Lung Tumor and Differentiation Antigens) with 3 morphologically similar prototype continuous-culture small-cell-carcinoma cell lines (SCC) (NCI-H69, NCI-H146, and NCI-H510). All cell lines had some reactivity with some of the MAbs. There is, however, differential expression of antigens amongst the prototype cell lines, which may provide a useful method for phenotyping and sub-classifying SCC. The reactivity of the 3 cell lines was greatest with MAbs in Clusters I, 1c, 2, 4, 6, and 9, and least with MAbs in clusters W7, 8, 13, 14, and W15, with few exceptions. Although morphologically similar, each of the SCC cell lines has a unique pattern of reactivity with the workshop MAbs. For example, although a control MAb, CD56 (NKHI), which identifies an epitope on NCAM (neural cell adhesion molecule) common among many SCC lines, stained more than 90% of cells in each of the prototype cell lines, one MAb of the current panel, SEN7, which also identifies a CD56 epitope on 15 SCC lines did not react as strongly with H-146 and H-510 as with H-69. If appropriately reactive MAbs can be identified for individual patients' tumors, they can be coupled to suitable radioisotopes or toxins for individualized patient treatment. PMID- 8194892 TI - Differentiation markers for lung-cancer sub-types. A comparative study of their expression in vivo and in vitro. AB - Cell lines representing the major sub-types of lung cancer have proved to be useful tools to study the molecular and cellular biology of these malignancies, provided that they are well established and well characterized. Antibodies directed against constituents of different cellular compartments can detect the type and degree of differentiation in lung cancer and derived cell lines. Antibodies can detect cell-surface adhesion molecules, such as NCAM, cadherins and integrins. NCAM antibodies are able to differentiate between small-cell lung cancer (SCLC) and non-SCLC, both in cell lines and in tumours. In addition, a spectrum of other membrane proteins, expressed in solid tumours, such as epidermal-growth-factor receptor and carcino-embryonic antigen, are retained in cell lines. Cytoplasmic intermediate filament proteins appear to be generally retained in lung-cancer cell lines, their combinations being the same as in solid SCLC, adenocarcinomas and squamous-cell carcinomas. Nuclear expression of lamins is comparable in tumours and in their corresponding cell lines and can be used to differentiate between SCLC and non-SCLC: A-type lamins, which are present in non SCLC, are absent in most SCLC. PMID- 8194893 TI - Statistical analysis of data from the Third International IALSC Workshop on Lung Tumor and Differentiation Antigens. AB - The main aim of the statistical analysis of data collected in the Third International IALSC Workshop on Lung Tumor and Differentiation Antigens, was to identify groups of monoclonal antibodies (MAbs) having similar profiles of reactivity against a variety of cell types in flow cytometry, histology, immunofluorescence and immunocytochemistry experiments. This was achieved through cluster analysis. We describe the methods used in the cluster analysis, and in the data processing leading to it. PMID- 8194894 TI - Evaluation of the binding properties of monoclonal antibodies submitted to Third International IASLC Workshop on Lung Tumor and Differentiation Antigens to Neural Cell Adhesion Molecule. PMID- 8194895 TI - NCAM and lung cancer. AB - The presence of the neural cell adhesion molecule, NCAM, is indicative for a poor prognosis in lung-cancer patients. Using MAb 735, we have investigated the expression of polysialic acid, PSA, on NCAM in a spectrum of neuro-endocrine lung tumors, ranging from the slowly growing typical carcinoids via the atypical carcinoids with clinically unpredictable behavior to the highly aggressive small cell lung carcinomas. Our immunohistochemical findings indicate a significant association between the presence of PSA on the tumor cells and an aggressive and immature sub-type of the tumor. This might be related to impairment of cell-cell and cell-matrix interactions by the presence of PSA, as we demonstrated in vitro, since detachment is one of the first steps in the metastatic process. The NCAM MAb 123C3 used in these studies appeared extremely useful in immunoscintigraphy and immunotherapy of SCLC xenografts in nude mice, and for immunoscintigraphy of a SCLC patient. This may be explained by internalization of the 123C3 antibody, which we demonstrated in vitro. 123C3 is the only Cluster-I SCLC MAb studied thus far that becomes internalized. PMID- 8194896 TI - A comparison of 67Cu- and 131I-labelled forms of monoclonal antibodies SEN7 and SWA20 directed against small-cell lung cancer. AB - The intact anti-SCLC monoclonal antibody (MAb) SEN7 and its F(ab')2 were labelled with the beta-emitting isotope 67Cu. Both materials retained their biological activity in vitro as determined by the Lindmo assay. In a direct comparison of in vivo distribution in a xenograph model, 131I- and 67Cu-labelled intact SEN7 showed similar absolute tumour accumulation. Blood levels were markedly lower in the case of the 67Cu-labelled antibody, resulting in improved tumour:blood ratios which reached a maximum of 13:1 compared with only 4.5:1 for 131I-SEN7. In the case of the 67Cu-labelled F(ab')2, very high accumulation of the nuclide was observed in the kidney. Levels of radio copper in liver and spleen were also found to be significantly raised when compared with radio iodine. SWA20, a MAb which had previously failed to show any selective in vivo accumulation in tumour xenografts when labelled with radio iodine showed higher and more stable tumour accumulation when labelled with 67Cu. PMID- 8194897 TI - Detection of small-cell-lung-cancer cells in bone-marrow aspirates by monoclonal antibodies NCC-LU-243, NCC-LU-246 and MLuC1. AB - We have used immunocytochemistry to identify tumor cells in bone-marrow aspirates of patients with small-cell lung cancer and we have compared the results with conventional histomorphology. The monoclonal antibodies (MAbs) used were NCC-LU 243 and NCC-LU-246 (cluster 1) and MLuC1 (cluster 6); 108 slides (52 patients) incubated with NCC-LU-246, 106 (51 patients) with NCC-LU-243 and 69 with MLuC1 (36 patients) were evaluated. Bone-marrow biopsies (83) were also obtained from 50 of these patients; 48/108 bone marrow aspirates were positive for cluster-1 antigen and 22/69 were positive for MLuC1. Immunocytochemistry with anti-NCAM MAbs detected bone-marrow localization in 38/83 bone-marrow aspirates compared with 9/83 bone-marrow biopsies, while MLuC1 was positive in 18/60 and bone-marrow biopsies in 6/60. Moreover, bone-marrow aspirates were positive for cluster-1 antigen in 7/17 patients with limited disease at diagnosis. Patients with positive bone-marrow biopsies had significantly shorter survival. No differences were found between patients with positive and those with negative marrow aspirates. PMID- 8194898 TI - Third International Workshop on Lung Tumor and Differentiation Antigens: overview of the results of the central data analysis. PMID- 8194899 TI - Detection of a putative 30-kDa ligand of the cluster-2 antigen. AB - The cluster-2 antigen, also called EGP-2, is a 38-kDa transmembrane glycoprotein with a distribution that is largely confined to human epithelial cells and their derived carcinomas. Monoclonal antibodies (MAbs) directed against EGP-2 have been extensively studied as anti-tumor agents, yet the function of the antigen is not known. In the present study we used a biotinylated recombinant soluble derivative of the EGP-2 (sEGPbio) as a probe to detect a possible EGP-2 ligand, using various carcinoma cell lines as a substrate. The recombinant soluble EGP-2 was expressed in the Autographa californica nuclear polyhedrosis virus (baculovirus) expression system. The sEGP-2, to which we engineered a poly-histidine affinity tag, was purified from infected Spodoptera frugiperda insect cells using immobilized metal-ion-affinity chromatography (IMAC). In Western blot analysis the sEGPbio probe bound to a 30-kDa protein band in 2 out of 5 of the assessed carcinoma cell lines, suggesting that this band may be an EGP-2 ligand. Interestingly, binding only occurred when, prior to SDS-PAGE, cell lysates had been subjected to a reducing agent (2-mercapto-ethanol). The physiological significance of this phenomenon and nature of the detected 30-kDa protein band remains to be determined. PMID- 8194900 TI - Difference in sero-diagnostic values among KL-6-associated mucins classified as cluster 9. AB - KL-6 classified as Cluster 9 (MUC-I) is a circulating high-molecular-weight mucin like molecule. Serum level of KL-6 was measured by a sandwich assay using KL-6 antibody as not only a catcher but also as a tracer. We established 2 additional monoclonal antibodies (MAbs), LISA 101 and EH-123, reacting with KL-6 epitopes different from the epitope recognized by KL-6 antibody. The KL-6-associated mucins detected by the sandwich assay using LISA 101 or EH-123 antibody as a catcher and KL-6 antibody as a tracer were designated as LISA 1-6 and CAM 123-6 respectively. The diagnostic values as the serum markers of KL-6, LISA 1-6 and CAM 123-6 were evaluated measuring their levels in the same serum from healthy individuals and from patients with pulmonary, pancreatic and breast adenocarcinomas. KL-6 was increased abnormally at high rates of more than 50% in pancreatic cancer and in benign lung diseases, LISA 1-6 only in pancreatic cancer, and CAM 123-6 only in pulmonary adenocarcinoma. In benign lung diseases, however, LISA 1-6 and CAM 123-6 were increased abnormally at the rates of only 5.3% and 0% respectively. These observations clearly indicate that LISA 1-6 and CAM 123-6 constitute a part of KL-6, but that they are superior to KL-6 as tumor markers for pancreatic cancer and for pulmonary adenocarcinoma respectively, because of their much lower false-positive rates. PMID- 8194901 TI - New anti-lung-cancer antibody cluster 12 reacts with human folate receptors present on adenocarcinoma. AB - Human folate receptor (hFR, folate-binding protein) is a single-chain glycoprotein with high specific affinity for folic acid and methotrexate. We have created 4 monoclonal antibodies (MAbs) to hFR, all of which react specifically with purified hFR in Western blots. Flow cytometry indicated that the antibodies all had patterns of reactivity against epithelial cell lines similar to that of antibody MW207 (workshop antibody 12), labeling 2 breast-tumor cell lines and 2 of 5 SCLC without labeling the one non-small-cell carcinoma tested. We used the antibodies to trace the in situ distribution of hFR in histologically normal tissues and in lung tumors by a sensitive alkaline-phosphatase-anti-alkaline phosphatase immunohistochemical technique. In frozen sections of normal lung, hFR was diffusely distributed on cell membranes of type-1 and type-2 pneumocytes and mucociliary and basilar respiratory epithelial cells of distal bronchi. The receptor was focally expressed by mucociliary cells of proximal respiratory mucosa and by macrophages, but was not detected in stromal smooth muscle, fibroblasts or lymphoid cells. In tumors, hFR was heavily and diffusely expressed on cell membranes of 9 of 10 pulmonary adenocarcinomas, 5 of 5 bronchioloalveolar carcinomas and 2 of 2 carcinoid tumors. It was focally expressed in 3 of 5 large cell lung carcinomas and was absent from 4 of 5 small-cell carcinomas, 18 of 22 invasive squamous carcinomas, 2 of 2 in situ squamous carcinomas, and 13 of 13 squamous dysplasias of bronchial mucosa. We conclude that hFR is heavily expressed in situ by normal alveolar and bronchial epithelium and by adenocarcinoma of lung. It is usually absent from small-cell carcinoma and squamous tumors at levels detectable by immunohistochemistry. PMID- 8194902 TI - Monoclonal antibodies directed against human tumor-associated antigens cross react with Drosophila proteins in clusters. AB - We reacted the Third International IASLC Workshop panel of monoclonal antibodies (MAbs) directed against human lung-tumor-associated epitopes with nitrocellulose blots of total proteins from adult fruit flies. Out of 63 MAbs tested, 9 showed a significant reaction with Drosophila proteins. Interestingly, in a double-blind analysis, most of the positive reactions fell into clusters that parallel the antibody reactivities against human tissues. In light of our findings, it becomes possible to screen expression vector libraries in order to isolate Drosophila cDNA that may have homology with human tumor-associated antigens. PMID- 8194903 TI - Characterization of cluster 13: the epithelial/carcinoma antigen recognized by MAb RS7. AB - Cluster 13 was defined by 2 independently derived murine monoclonal antibodies (MAbs), RS7 (IgG1) and MR54 (IgG2a), which were raised against human squamous cell carcinoma of the lung and a human ovarian-carcinoma cell line, respectively. Immunologic and biochemical evidence demonstrated that RS7 and MR54, as well as 2 additional MAbs, MR6 (IgG2a) and MR23 (IgG1), generated in the same fusion as MR54, recognize the same antigen, a 46- to 48-kDa glycoprotein. Evaluation of the expression of antigen on the surface of tumor cell lines, Western blotting analyses, competitive binding studies, and double-determinant ELISA assays, support this conclusion. Two distinct epitopes are defined by these MAbs. In order to further characterize this antigen, amino-acid-sequence analyses were performed on peptides derived from antigen purified by affinity chromatography with MAb RS7. The sequence data obtained from 2 peptides, which were independently generated by CNBr cleavage and trypsin digestion respectively indicated identity to GA733-1. The GA733-1 genomic DNA sequence predicted a type 1 membrane protein of 35 kDa, with 4 potential N-linked glycosylation sites. The GA733-1 protein product has not been identified previously, and MAbs to this tumor-associated antigen were not previously known. PMID- 8194904 TI - New pathways in an age of ecological and ethical concerns. PMID- 8194905 TI - Geographical differences and time trends in the seasonality of birth in Japan. AB - Seasonal variations of births in six different prefectures in Japan are analysed using Vital Statistics from 1974 to 1983. First births show a bimodal pattern with two peaks, one in winter (December-February) and the other in summer to early autumn (August-September). The seasonality of first births is statistically significantly correlated with the seasonality of marriages with 9 + 12*n (n = 0, 1, 2, 3) lag months. For subsequent births, the seasonal pattern is unimodal and there is also a geographical trend in seasonality of these births with a late spring peak in the northernmost prefecture of Japan giving way to an early autumn peak in the southernmost prefecture. These findings suggest that seasonal variations in marriage play some role in the seasonality of first births, while other features such as environmental factors could be associated with the seasonal variations of subsequent births. Changes in the seasonality of both births and marriages over time suggest that the modernization of Japanese society after the second World War could be responsible for the drastic changes in the pattern and degree of seasonality of births. PMID- 8194906 TI - Differences in gestational age-specific birthweight among Chinese, Japanese and white Americans. AB - This study investigated racial differences in gestational age-specific birthweight in a sample of 21,288 Chinese, 11,882 Japanese and 65,818 White resident singleton livebirths, obtained from the National Center for Health Statistics 1983 and 1984 linked birth/infant death cohort files. The gestational age-specific birthweight distributions of Chinese and Japanese were similar, but differed from those of Whites both in the mean level and in the variance. The mean birth-weights of Chinese and Japanese as compared to that of White infants were 4-5% lower among preterm births, and 5-6% lower among term births, after adjustment was made for gestational age, demographic variables, use of antenatal care and infant gender. The racial differences in gestational age-specific birthweight were even greater at the 90th percentile but smaller at the 10th percentile. These racial differences should be considered in both clinical evaluation of newborns and in epidemiological studies. Significant interactions were found between race and such maternal variables as education, marital status, birthplace, and month during which antenatal care began. It suggests that recognition of racial differences in risk factors and exposure-response relationships may be valuable in specifying interventions for intrauterine growth retardation among different racial groups. PMID- 8194907 TI - Differences in mortality and coronary heart disease between Lithuania and The Netherlands: results from the WHO Kaunas-Rotterdam Intervention Study (KRIS). AB - BACKGROUND: A 9.5-year follow-up of the Kaunas-Rotterdam Intervention Study (KRIS) provided an opportunity to compare mortality patterns and rates in a population from Lithuania, one of the former republics of the Soviet Union, with a population from the Netherlands. These populations consisted of 2452 and 3365 males, respectively, aged 45-60 years. In 1972-1974, these males were extensively screened for cardiovascular risk factors, using uniform methods. METHODS AND RESULTS: During the follow-up, 303 males in Kaunas (Lithuania) and 350 males in Rotterdam (the Netherlands) died. Using Cox proportional hazards and logistic regression analysis, it was found that all-cause mortality rates during follow-up were 30% higher in Kaunas; this was mainly due to higher mortality rates from external causes (relative risk = 6.69), stomach cancer (RR = 2.78), stroke (RR = 2.30) and infectious diseases (RR = 12.43). The risk of fatal and non-fatal coronary heart disease (CHD) was, however, smaller in Kaunas (RR = 0.72). This lower risk closely corresponded with the Lithuanian risk profile which could be described by less smoking, lower cholesterol levels, and higher physical activity. As Lithuanians had a more advantageous cardiovascular risk profile, the higher Lithuanian all-cause mortality rates could not be explained by this risk profile. CONCLUSIONS: The results provide evidence for geographical differences in mortality and morbidity between Lithuania and the Netherlands. Population specific health behaviours were shown to be involved in differences in the risk of CHD. The lower CHD rates in Eastern European communities in the 1970s, in this study confirmed for Lithuania, suggests that the apex of the CHD epidemic had not yet reached the Lithuanian population. PMID- 8194908 TI - Infant feeding in Bolivia: a critique of the World Health Organization indicators applied to demographic and health survey data. AB - Infant feeding is a multidimensional activity that can be described and analysed in many different ways. The World Health Organization (WHO) has recently issued recommended indicators for assessing infant feeding practices. This paper presents these indicators and demonstrates their applications using the 1989 Demographic and Health Survey (DHS) data for Bolivia. The results indicate that, although most Bolivian infants are breastfed and two-thirds are breastfed for > 1 year, supplementary feeding practices deviate considerably from international recommendations. Only 58% of infants < 4 months old are receiving breastmilk alone (the 'exclusive breastfeeding rate') and a similarly low percentage (54.7%) of 6-9 month olds are receiving the recommended combination of breast milk plus solid or semi-solid foods (the 'timely complementary feeding rate'). Furthermore, almost half of breastfed infants < 12 months old are also receiving bottle feeds. The infant feeding practices of city residents are least likely to conform to the infant feeding recommendations, while practices of mothers who have always lived in the country are most likely to be similar to the WHO guidelines. Mothers who have moved to the city since the age of 12 are most likely to be giving their infants other milks in addition to breast milk and to be bottle feeding their infants. The WHO infant feeding indicators provide a useful framework for quantifying infant feeding practices, and most of the indicators can readily be applied to DHS data. Nonetheless, improvements can be made in both the indicators themselves and the DHS questionnaire to improve reporting of internationally comparable infant feeding information. PMID- 8194909 TI - Space-time clustering in insulin-dependent diabetes mellitus (IDDM) in south-east Sweden. AB - Using the method developed by Knox, space-time clustering was analysed in all 584 cases of insulin-dependent diabetes mellitus (IDDM) diagnosed between 1977-1990 and below the age of 16 from four paediatric departments in south-east Sweden. The catchment areas of these clinics form a contiguous geographical area of 26,445 km2 with a total of 165,784 children aged 0-15 years. The annual incidence for the study period was 25.2 per 100,000 children aged 0-15 years with a statistically significant incidence variation between the years; highest incidence in 1983 (39.2) and lowest in 1977 and 1989 (18.9 and 20.7 respectively). In the analysis, 30 different combinations of critical cutoff values were used to define closeness in space and time of pairs of cases. Statistically significant results were seen for several combinations with the highest significance obtained for the cutoff values of 15 km and 7 months, respectively. This space-time clustering tended to be specially pronounced during the period with the highest incidence of IDDM, 1981-1985. Our results indicate that space-time clustering exists in IDDM. These findings may support the hypothesis that infectious agents (possibly viral) give rise to a portion of IDDM. PMID- 8194910 TI - Secular trends in mortality from asthma in Japan, 1979-1988: comparison with the United States. AB - To determine whether mortality from asthma in Japan has increased, and to examine the age-, sex-, and race-specific mortality rates from this disease and their secular trends in both Japan and the US, vital statistics from 1979 through 1988 were studied. Overall, rates were highest among Japanese and decreased from 1979 to 1988, while rates in the US were lower and increased somewhat, especially among Blacks (whose rates were intermediate, in general, between Japanese and US Whites). Age-specific rates showed the greater asthma mortality in Japan to be due to deaths at ages greater than 50 or 60 years. The downward trend in the Japanese, unlike US Blacks and Whites, was due specifically to decreasing rates among the youngest and the oldest age group between the earlier and later years of the period, 1979-1988. PMID- 8194911 TI - Validation of self-reported neurological disability in multiple sclerosis. AB - In all 129 unselected patients with multiple sclerosis (MS) completed a 25 item auto-questionnaire for assessment of disability. Each patient was examined on the same day by a neurologist who was blind to patients' answers and gave Expanded Disability Status Scale (EDSS) scores. From the auto-questionnaire, eight scores were obtained, one for each of the seven functional systems rated by the EDSS and the eighth relating to walking difficulties. Analysis showed that correlation between patients' self assessments and the neurologist's ratings was high (r > 0.50) for five out of the eight scores and low for three, especially for brainstem and mental functions which were excluded from subsequent analysis. Using a linear regression model, it was possible to predict the EDSS scores given by the neurologist (+/- 1 point) from patients' answers in 73% of the cases. The performance of the model was robust and was not influenced by patients' characteristics (sex, age, disease course). This study shows that most aspects of MS disability can be self-assessed by patients, and suggest a useful approach when it is not feasible to examine each MS patient as in large community-based studies. Collaborative studies for defining and validating auto-questionnaires on disability should be encouraged. PMID- 8194912 TI - Appendicectomy for acute appendicitis and for other conditions: an epidemiological study. AB - BACKGROUND: Appendicectomy is one of the commonest operations in most developed countries, especially in children and young adults. We used routine abstracts of hospital inpatient records to study the demographic and temporal profiles of emergency appendicectomy for acute appendicitis and appendicectomy in other circumstances. METHODS: Records held in the Oxford record linkage study (ORLS) from 1970-1986 inclusive were analysed. Age- and sex-specific admission rates were studied, subdividing appendicectomy into three main categories: emergency appendicectomy for acute appendicitis, emergency appendicectomy as the main operation without appendicitis recorded as a diagnosis, and prophylactic or incidental appendicectomy with other operations but without appendicitis. RESULTS: A total of 47,505 records of appendicectomy were analysed. Emergency appendicectomy for acute appendicitis was more common in males than females, peaked in the 10-19 year age groups, and declined over time. Emergency appendicectomy without appendicitis was more common in women than men (female to male ratio 1.8:1), peaked at age 15-19 years and did not decline over time. Incidental appendicectomy was much commoner in women (female to male ratio 3:1), peaked at older ages than the first two groups, and declined significantly over time. CONCLUSIONS: The demographic profiles of patients in these categories were quite different. The data on trends suggest confirmation of a true decline in acute appendicitis, no decline for conditions which may mimic it, and a decline in the use of prophylactic and incidental appendicectomy. The operations in the latter categories--appendicectomy without acute appendicitis--were much commoner in women than men and their appropriateness would be worthwhile topics for medical audit. PMID- 8194913 TI - DNA probes as epidemiological tools for surveillance of Plasmodium falciparum malaria in Thailand. AB - We have previously reported on development of a DNA probe-based method for diagnosing Plasmodium falciparum infection directly from patient blood samples. In the present studies, we sought to examine applicability of the method to large epidemiological surveys, comparing sensitivity, specificity, time required to obtain results, and costs with those of conventional microscopic examination. Results of DNA probe hybridization were also compared between laboratories in the US and Thailand, to assess transferability of the DNA probe technology. Five separate surveys of approximately 5000 villagers each were performed between December 1987 and June 1989 (26,176 samples total). Sensitivity ranged from 61% to 92% for both US and Thai laboratories, while specificity ranged from 98.2% to 99.9%. Agreement between the US and Thai laboratories was good, with kappa coefficients between 0.62 and 0.78 for different surveys. Between 4 and 8 person days were required to obtain results from each set of 5000 samples by DNA hybridization, whereas microscopic examination required 150 person-days. Approximate costs were US 0.17 per sample for DNA probe analysis, and US$0.36 for microscopic examination. We conclude that the DNA probe method offers significant advantages when large numbers of samples must be surveyed for P. falciparum. PMID- 8194914 TI - Chlamydia pneumoniae IgG antibody prevalence in south-western and eastern Finland in 1982 and 1987. AB - Chlamydia pneumonia IgG antibody prevalence was examined in a representative sample (2342 subjects) of the population aged 25-59 years in south-western and eastern Finland in 1982 and 1987. Microimmunofluorescence was used to measure IgG antibodies. Prevalence of C. pneumoniae was modelled using the GLIM statistical package assuming that the prevalence had a binomial distribution. The prevalence was assumed to be a function of the year, subjects' gender, age and place of residence. The effect of the year on the prevalence was significant in both regions (P < 0.05 in the south-west and P < 0.001 in the east). In each year the prevalence was higher in the south-west than in the east and it increased between 1982 and 1987 from 55% to 63% in the south-west and from 41% to 59% in the east. The prevalence increased with age, but the age-related antibody pattern was different between sexes. The highest prevalence was found in men aged 49-59 years. The different increase in prevalence with age in the south-western and the eastern parts of the country indicates that the outbreaks of infection were not related. The endemic level of C. pneumoniae infection in the south-west is consistently higher than in the east, or there was an outbreak of C. pneumoniae infection in both the years we examined. Thus it is more likely that the high prevalence in south-western Finland was connected more with the epidemics reported elsewhere in Scandinavia in the same years than with the occurrence of C. pneumoniae infection in eastern Finland. PMID- 8194915 TI - A 'post-honeymoon period' measles outbreak in Muyinga sector, Burundi. AB - In Muyinga sector, Burundi, an area with good vaccination levels against measles and recent low incidence of measles, a major outbreak of measles in 1988 raised questions about the efficacy of the immunization programme. To help answer these questions, we 1) reviewed programme data on doses of measles vaccine administered, vaccine coverage, and measles incidence, and 2) conducted a census of the affected area to examine vaccine efficacy and measles mortality. We found that between 1980 and 1988 in Burundi, 1) measles vaccine coverage by age 1 had increased from 0% to 55%, 2) the incidence of reported measles cases declined from 12.1/1000 to 6.2/1000, 3) reported measles mortality dropped from 0.18/1000 to 0.08/1000, and 4) the interepidemic period had increased from 25 to 35 months. In the census, the best estimate of measles vaccine efficacy administered at 9 months of age was 73%. Measles increased the risk of death by 2.5-fold with the effect limited to the first month after measles. This outbreak demonstrated the 'post-honeymoon period' epidemic predicted by mathematical models in which outbreaks occur among accumulated susceptibles in a partially immunized population. Understanding this phenomenon is important in providing a basis for improved strategies of measles control. Such outbreaks present new challenges to newly maturing immunization programmes in improving skills in surveillance, outbreak investigation, and public relations. PMID- 8194916 TI - Data utilization and analytical skills among mid-level health programme managers in a developing country. AB - Mid-level health managers in a developing country were studied to examine the extent to which they are able to use and analyse data they receive from a new health information system. Among 168 managers filling out a self-administered questionnaire, 52% could compute a simple cost-effectiveness ratio and 27% were able to calculate proportions. Only 43% of the managers were able to construct a cumulative graph similar to the one recommended by WHO. Facility with these tasks was not related to levels of training or age. Twelve out of 25 programme managers interviewed in depth did not know how well their particular programme had performed in the previous year. Similarly, only six of these managers knew their best and poorest performing districts. The results of this study suggest; 1) Training managers in data analysis and use is critical if health information systems are to actually improve health care delivery. 2) Data intended for the use of programme managers need to be presented in simple ways. 3) Further social research is required to understand how managers perceive and use data. 4) Efforts to ensure the use of data should not be seen as something to be 'added on' after information systems are in place. PMID- 8194917 TI - Comparison of serum lipoprotein(a) distribution and its correlates among black and white populations. AB - BACKGROUND: Epidemiological data on serum lipoprotein(a) (Lp(a)), a presumably strong risk factor for coronary artery disease in White populations, has mostly been derived, in Black populations, from small samples. This study compares the distribution and the determinants of serum Lp(a) in Blacks and in Whites using large representative samples and the same methods in both populations. METHODS: The distribution and the correlates of serum Lp(a) were investigated in population-based samples of 701 Blacks in the Seychelles and 634 Whites in Switzerland, aged 25-64 years. Serum Lp(a) was quantified using a commercial immunoradiometric assay. RESULTS: The distribution of serum Lp(a) was similarly skewed in both ethnic groups, but median Lp(a) concentration was about twofold higher in Blacks (210 mg/l) compared to Whites (100 mg/l). The proportions of individuals with elevated serum Lp(a) (> 300 mg/l) was about 50% higher in Blacks (37.5%) than in Whites (25.2%). In both ethnic groups, serum Lp(a) was found to correlate with total cholesterol, LDL-cholesterol and apoprotein B but not with HDL-cholesterol, alcohol intake, smoking, and body mass index. The variance in serum Lp(a) concentration explained by any combination of these factors was smaller than 5.3% in the two populations. CONCLUSIONS: The measured factors did not explain the higher levels of serum Lp(a) found in Blacks compared to Whites. These findings are consistent with the hypothesis that genetic factors account for much of the variation of serum Lp(a) in both populations. PMID- 8194918 TI - Odds ratio or relative risk for cross-sectional data? PMID- 8194919 TI - Ascertainment corrected rates. PMID- 8194920 TI - Coronary risk in a British Punjabi population: comparative profile of non biochemical factors. AB - OBJECTIVES: To develop a profile of non-biochemical coronary risks for the South Asian population (predominantly Punjabi with origins in the Indian subcontinent) and the general population in Glasgow, with a focus on dietary patterns, and potential causes of stress. DESIGN: Cross-sectional survey of South Asian men and women of 30-40 years (mean 35), compared with a general population sample aged 35 years. MEASUREMENTS: Data were collected on socioeconomic circumstances, smoking, diet, alcohol, exercise, past health, perceptions of stress and other psychological morbidity, blood pressure, height, weight and waist and hip girth. RESULTS: The socioeconomic circumstances of the South Asian group were worse than the general population. The prevalence of several circumstances potentially associated with stress, such as length of working day, low income, crowded housing, liability to attack and perceived lack of social support (women), was greater in South Asians. Smoking was less common in South Asians, particularly among women and non-Muslims. Amongst South Asians, alcohol use was uncommon in women and Muslims. South Asians ate meat, and fruit, salad and raw vegetables more frequently than the general population though there were large variations by religion. South Asian men were less likely to take vigorous exercise than the general population. Diastolic, but not systolic, blood pressure was higher in South Asian males than general population males, but there were no differences among women. Men were shorter and weighed less than general population men, with no difference in body mass index. South Asian women were shorter but had higher mean body mass index than the general population. Waist and hip circumference in both South Asian men and women were higher although waist/hip ratios were not different. Self-reported diabetes was commoner in Asian men than in general population men, and angina symptoms commoner in South Asian women. CONCLUSIONS: Among established risk factors studied here or reported in an earlier paper the only one to which South Asians had less exposure was smoking. In either men or women (or both) there was a relative excess of the other known risk factors. There was evidence in support of three newer hypotheses for the high incidence of coronary heart disease (CHD), namely, insulin resistance, stress, and socioeconomic deprivation. The high CHD rates in South Asians are likely to result from a complex interaction of risk factors. PMID- 8194921 TI - Serum albumin and mortality in the BUPA study. British United Provident Association. AB - In the British United Provident Association (BUPA) study, a prospective observational study of 21,520 men, the serum albumin of 877 men who died during 10 years of follow-up was compared with that of 877 controls, each matched to a case by age (within 1 year) and date of attendance (within 3 months). There was little overall difference (mean case-control difference = -0.11 milligram, P > 0.2) despite the fact that other studies have reported a long-term association between low serum albumin and increased mortality. Cause-specific mortality data showed no association of low albumin with ischaemic heart disease or other circulatory diseases. An inverse association with cancer was confined to the first few years of follow-up and so attributable to pre-clinical cancer lowering both serum albumin itself and serum cholesterol, with which albumin was associated. There was an association of chronic respiratory, neurological, renal, liver and gut diseases with low serum albumin (case-control difference = -1.19 milligram, P < 0.001) consistent with the effect of pre-clinical disease lowering serum albumin. Other causes of death showed no association with albumin. Our data do not support a cause and effect association of low serum albumin and mortality. PMID- 8194922 TI - Cigarette smoking as a potential cause of cervical cancer: has confounding been controlled? AB - It is widely believed that some sexually transmitted pathogen plays a key role in the aetiology of cervical cancer. However, although certain human papilloma viruses are strongly implicated, the pathogen responsible and its mechanism of action remain to be finally characterized. The correlation between cigarette smoking and sexual activity that exists in most cultures therefore makes evaluation of the potential additional role of smoking difficult, due to confounding with the presence of the aetiological pathogen. Epidemiological studies of the association between smoking and cervical cancer have adjusted for the lifetime number of sexual partners as a proxy measure of the presence of the pathogen and, in most cases, the association has diminished but remained statistically significant. Since the use of a proxy will tend to result in underestimation of the effect of the aetiological pathogen on risk of cervical cancer, however, the adjustment is likely to be insufficient, thus resulting in overestimation of the adjusted or 'independent' effect of smoking. In an attempt to address this concern we used a simulation approach to investigate whether a substantial 'independent' association between smoking and cervical cancer might be expected as a result of the use of a poor proxy for the aetiological pathogen, even if there is no true effect of smoking. Using realistic estimates of the association between the presence of the aetiological pathogen and both smoking and risk of cervical cancer, 'independent' relative risks for cigarette smoking of two and above were generated. It is therefore plausible that the observed 'independent' effect of cigarette smoking on cervical cancer is due to residual confounding. PMID- 8194923 TI - Changes in major risk factors for cardiovascular diseases over 25 years in the Serbian cohorts of the Seven Countries Study. AB - The Serbian cohorts of the Seven Countries Study were examined four times during a 25-year period. Large changes were observed in average serum cholesterol, blood pressure and the prevalence of smoking in these ageing cohorts. Comparison of men of the same age strata e.g. men aged 50-59 examined at baseline and after 10 years of follow-up and of men aged 65-69 examined after 10 and 25 years of follow up showed that serum cholesterol increased by about 45% in Zrenjanin, 35% in Velika Krsna and 15% in Belgrade over the last 25 years. Systolic blood pressure increased by 9% in Zrenjanin and 7% in Velika Krsna. No significant increase in systolic blood pressure was observed in Belgrade. There was no major secular trend in smoking and the changes observed during 25 years were mainly due to ageing. No major change was observed in body mass index. The increases in serum cholesterol and blood pressure observed in the Serbian cohorts during the last 25 years are compatible with the increase in cardiovascular disease mortality observed in Yugoslavian men aged 30-69 during the period 1970-1984. PMID- 8194924 TI - Alcohol consumption and colon and rectal cancer in postmenopausal women. AB - The associations between alcohol and colon and rectal cancers were examined in the Iowa Women's Health Study. In January 1986, 41 837 postmenopausal women, aged 55-69, completed a questionnaire including usual alcohol intake and other information. Through December 1990, 237 incident colon and 75 rectal cancer cases occurred. Mantel-Haenszel age-adjusted relative risks (RR) and 95% confidence intervals (CI) for consumers of < 4.0 and > or = 4.0 g of alcohol per day compared to abstainers were 1.07 (0.61-1.89) and 1.27 (0.72-2.24) (P for trend = 0.46) for rectal cancer. Alcohol intake was inversely associated with distal colon cancer (RR for < 4.0 and > or = 4.0 g of alcohol per day were 0.64 and 0.69 respectively, P for trend = 0.04), which was specific to wine; however, no association was observed with proximal colon cancer (P for trend = 0.94). This is the only report of an inverse association between alcohol and colon cancer in women. Because gut physiology and alcohol metabolism differ between men and women, more research on the association between alcohol and colon cancer in women only, is warranted. PMID- 8194925 TI - Occupation and bladder cancer in Pordenone (north-east Italy): a case-control study. AB - This case-control study evaluated the relationship between bladder cancer and occupational factors in an area of North-east Italy. The study included 273 bladder cancer cases and 573 controls identified through the services of local hospitals. Information on socio-demographic characteristics, past medical history, lifestyle factors, employment in certain industries and occupational exposures was obtained by interviewing study subjects. Elevated relative risks (RR), albeit not statistically significant, were found among males ever employed in the general chemical (RR = 2.8), dye (RR = 6.9) and painting (RR = 3.1) industries. When results related to the general chemical and specialty chemical industries were combined the RR was 3.1 (95% confidence interval [CI]: 1.2-8.5). The RR increased with increasing duration and decreasing age at starting and years since quitting employment. The risk was significantly decreased for subjects ever employed in agriculture (RR = 0.6 for males, 0.5 for females), livestock farming (RR = 0.5 for males, 0.4 for females) and furniture manufacturing (RR = 0.5 for males), whereas an elevated risk was found among white collar workers (RR and 95% CI: 1.5, 1.1-2.4 and 2.7, 1.1-6.6 for males and females, respectively). These results confirm a well-known risk among subjects employed in various sectors of the chemical industry, and indicate that bladder cancer is associated with urbanization indicators. Because lifestyle factors (i.e. smoking, coffee consumption, etc.) did not totally explain the results for white collar workers, it is possible that other still undefined aspects of the urban environment play a role in bladder carcinogenesis. PMID- 8194926 TI - A time-series analysis of trends in firearm-related homicide and suicide. AB - In order to determine whether firearm use was an increasing component of the general pattern of homicide in Cape Town, South Africa, hidden Markov time-series models were used to examine a week-by-week count of firearm homicides, non firearm homicides, firearm suicides and non-firearm suicides for the 6-year period from 1986 to 1991. Of several models fitted to the proportion of homicides that involved firearms, the one which incorporated a discrete upward shift in the middle of 1991 was the most successful. There was no evidence of a similar upward shift in the proportion of the suicides that involved firearms. The sharp increase in 1991 in the probability that a homicide involved the use of a firearm is consistent with a reported upsurge in violence related to the so-called 'taxi wars'. Hidden Markov models, as a general methodology for the analysis of discrete-valued time series, may be a useful and flexible means of identifying time trends or points of transition related to events or interventions in a wide range of public health contexts. PMID- 8194927 TI - Patterns of mortality in Western Australian aboriginals, 1983-1989. AB - The ratios of age-standardized mortality rates of Aboriginals to non-Aboriginals in Western Australia during the period 1983-1989 were 2.6 for males and 3.0 for females. Mortality rates experienced by Aboriginals were much higher in all age categories except 75+ years and for most major diseases except neoplasms. The peaks of all-cause age-specific mortality rate ratios (RR) for Aboriginal males and females were 10.2 (at 40-44 years) and 10.0 (at 35-39 years), respectively. These excess mortalities were mainly due to circulatory diseases, injury and poisoning, respiratory diseases and, in females, to digestive diseases and genitourinary diseases. The highest age-standardized, cause-specific RR for Aboriginal males were for mental disorders (10.3), injury and poisoning (8.9) and genitourinary diseases (8.6); for females the highest RR were for genitourinary diseases (16.9), endocrine, nutritional and metabolic (mainly diabetes mellitus) (12.3), and for infectious and parasitic diseases (7.5). PMID- 8194928 TI - Finnmark Heart Study: employment status and parenthood as predictors of psychological health in women, 20-49 years. AB - This study examined the influence of employment status and presence of young children in the household on psychological health in a population-based sample of 3103 women aged 20-49 years. Women were classified by employment status and parental status, thus creating four groups for comparison. After excluding women reporting chronic diseases and women receiving sickness, rehabilitation, unemployment or disability benefits, analyses indicated that problems of coping, dissatisfaction with life, depression and loneliness were greatest among homemakers, particularly among those with young children. Analyses adjusted for age, education, marital status and place of residence yielded similar results. Stratification by marital status and place of residence revealed two exceptions to this general pattern: unmarried employed women with young children had the highest rate of coping problems--and parenthood, not employment status, was the most important factor for psychological health problems in rural areas. Discrepancies between an individual's behaviour and the norm in society regarding women's employment, may partly explain the findings. PMID- 8194929 TI - Differences in self-reported morbidity by marital status and by living arrangement. AB - It has frequently been shown that the never married, divorced and widowed have higher rates of self-reported morbidity than married people. The purpose of this study was to assess to what extent morbidity differences by marital status can be explained by differences in living arrangement (i.e. living with a partner or not). If living arrangement plays a major role, one expects to find that: 1. people who live with a partner have lower morbidity rates than those who live alone; 2. morbidity differences by marital status decrease substantially after controlling for living arrangement. Data from the GLOBE study, a large prospective cohort in the Netherlands, on 18,973 people from Eindhoven and its surroundings, aged 15-74, were used to test the hypotheses. The measures for morbidity were perceived general health, subjective health complaints, chronic conditions and work disability. Multiple logistic regression models were used to calculate odds ratios for morbidity by living arrangement (question 1) and for morbidity by marital status, firstly without control and subsequently with control for living arrangement (question 2). In all models we controlled for other sociodemographic variables (age, sex, educational level, degree of urbanization, religion and country of birth). Our analyses showed that people who live with a partner have lower morbidity rates than those who live alone. They further showed that the excess risks of the never married, widowed and divorced decreased by 40-70% for all health measures (except subjective health complaints) after controlling for living arrangement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8194930 TI - Work satisfaction and health in the middle-aged and elderly. AB - BACKGROUND: There is evidence that occupational factors that cause psychological strain can affect physical and mental health, but findings are not consistent. METHODS: Work satisfaction was used as a convenient global index of job-related psychological strain. Relationships with general, physical and emotional health, appraised by the use of questions, were examined in workers aged > or = 50 years in a longitudinal community health study in Jerusalem. RESULTS: Positive associations were found both in 1975-1976 and in 1985-1987, with age, origin, education, sex and other variables controlled. The odds ratio in favour of poor general health was 2.8 times as high in dissatisfied workers as in very satisfied ones. Multivariate analyses suggested that the associations were not spurious ones attributable to a proneness to report both dissatisfaction and ill-health. Workers who expressed dissatisfaction in both 1975-1976 and 1985-1987 were particularly unhealthy in 1985-1987. CONCLUSIONS: The findings support the impact of work satisfaction or its determinants on current health, and suggest that persistent dissatisfaction may be especially deleterious to health. PMID- 8194931 TI - Action research: a strategy for theory generation and testing. AB - We define action research and relate it conceptually to other research strategies. The inadequacy of some action research methodologies for theory generation and testing is discussed. We describe the way we re-dressed this deficiency in our study of the journey from traditional nursing to patient centered nursing. The differences and tensions between "research-thinking" and "practice-thinking" are explored and we show how our research partnership balances the two ways of thinking. We suggest that operating within the research criteria, presented here, may help action researchers to conduct rigorous research, as well as to improve practice. PMID- 8194932 TI - Stress in midwifery: a comparison of midwives and nurses using the Work Environment Scale. AB - Previous research into midwifery has identified a number of potential sources of stress without attempting to understand the variables that might contribute to it. The study sample was drawn from a population of registered nurses and midwives and compares the work environment of 29 midwives with 180 nurses, using the Work Environment Scale Questionnaire. Significant differences were found between midwives and nurses for involvement, supervisor support, autonomy, work pressure and clarity of roles. These results have the potential for forming the basis of future research. PMID- 8194933 TI - Client-nurse interaction: testing for its impact in preoperative instruction. AB - This study tests for the impact of client-nurse interaction, an essential element lacking in earlier research on preoperative instruction. An experimental design compared the effects of three models of intervention: Facilitator, Informational and Routine Treatment on postoperative pain and anxiety in 91 cholecystectomy patients. Planned comparisons showed that subjects in both experimental conditions reported significantly less postoperative anxiety than subjects who received the routine treatment. There were no differences in anxiety levels between the two experimental groups or in pain scores among the three groups. Refinements in the facilitator model are recommended to enhance the problem solving nature of the interaction and to strengthen future research. The findings support the importance of providing the patient with sensation information and postoperative exercise instruction. PMID- 8194934 TI - The JAND (Judgment About Nursing Decision) as a measure of nurses' perception of moral behaviors. AB - A comprehensive review of research using the Judgment About Nursing Decisions (JAND) as a measure of nurses' ethical decision making raises numerous concerns about the conceptual basis, reliability, and validity of this widely used instrument. These concerns promoted the present study, which raised specific issues about the JAND. Among these issues are the representatives of ethical dilemmas contained in the JAND, the validity of its scoring scheme, the persistence of low-to-marginal reliability across studies, and questionable validity. Findings from studies using the JAND should be interpreted with caution until the instrument is further refined. PMID- 8194935 TI - Effectiveness of knee replacement surgery in arthritis. AB - This study examined the effectiveness of knee replacement surgery in an elderly population suffering from arthritis. Four questionnaires which measured pain, mobility, anxiety, depression and social isolation were completed by the study group before and after surgery to assess changes in physical function, psychological state, social interaction and somatic sensation. A statistically significant difference was found in pain which was reduced from a median score of 3 before the operation to 0 afterwards on an intensity scale of 0-5. Statistically significant improvements were also found in the mobility/dependency scores and in the level of anxiety and depression following the operation. It was concluded that knee replacement is a highly effective treatment for arthritis of the knee, reducing pain, increasing mobility and improving the persons emotional state, thus improving the quality of life of the recipient. The use of separate questionnaires to measure single dimensions of quality of life as opposed to a single health profile is also discussed. PMID- 8194937 TI - Attitude change amongst nursing students towards Australian aborigines. AB - A pre-test and post-test impact evaluation design was used to determine if attendance at a workshop conducted by Australian aboriginal health personnel improved the attitudes of nursing students towards Aborigines. A three-hour workshop attended by first year nursing students comprised an introduction, video and discussion. A self-administered questionnaire, consisting of socio demographic background questions and attitude rating scale, was used to measure students' attitudes before and after the workshop. The Wilcoxon signed rank test and paired t-test were used to test for significant improvement in students' total attitude scores. Multiple regression analysis was conducted to determine if socio-demographic variables contributed to the changes in the students' attitude scores. Complete data were collected from 246 students. Results indicate improvement in attitude scores. Socio-demographic variables did not contribute to these scores. PMID- 8194936 TI - The impact of the medical model on nursing practice and assessment. AB - In its extreme form, the medical model with its concerns of diagnosis, treatment and cure, has been criticized for the narrow and unsatisfactory view it takes of health care. Proponents of nursing theory, in contrast, attempt to develop a conceptual structure which offers a more humanistic approach to patient care, where nurses attempt to move beyond the influences of medical values in the way that they work. This study indicates, however, that the medical model is occasionally compatible with nurses' values, and in certain settings can enhance and support nursing care. In other settings, however, the medical model, although in accord with nursing values, has little to offer practice, and indeed may have a negative effect on the development of alternative approaches to care. PMID- 8194938 TI - The knowledge, attitudes and perceived support of Tanzanian nurses when caring for patients with AIDS. AB - In the literature on AIDS, much attention has been paid to the Western health care workers' knowledge of and attitudes toward AIDS. Little is known of the knowledge and attitudes of health care workers of developing countries. This study provides a descriptive and comparative examination of Tanzanian nurses' knowledge of, and attitudes towards AIDS and their perceived support when caring for patients with AIDS. A self-completing questionnaire was used to collect data. Questionnaires were completed and returned by 172 of the 180 nurses to whom they were distributed, a response rate of 95.5%. A random sample of 45 nurses was chosen from each hospital--two teaching and two regional hospitals. Data analysis included descriptive statistics, t-test, correlation coefficient, ANOVA and multiple regression. The research revealed that 96% of Tanzanian nurses appeared to have a satisfactory or passing level of knowledge about AIDS. However, they are overly cautious and have negative attitudes toward the care of patients with HIV/AIDS. They lacked knowledge regarding transmission and risk factors and indicated fear of contagion (AIDS-phobia). Most nurses indicated that they had a supportive working environment (informal support groups) in their working areas, but few formal supports and little in-service education. Further, they received support from their family and friends. PMID- 8194940 TI - Evaluation of the Congruence Model with rehabilitating substance abusers. AB - The Congruence Model was used with families of indigent substance abusers. Instead of a focus on pathology, this nursing approach advocated ethnically congruent coping of families within their environment. Forty participants worked on individually chosen goals during eight structured sessions. Evaluation included goal attainment analysis and a comparison of the treated families with families in self-help groups and a control group. Treated families made significant progress with personal and family goals. Treatment and support group families reported better family functioning at one month and fewer relapses two to three months after treatment. The Congruence Model seemed particularly effective if families sought help but did not opt for support groups. PMID- 8194939 TI - Family dynamics during the third trimester of pregnancy in Denmark. AB - Family dynamics in Danish families during the third trimester of pregnancy were explored in relation to family structure, parity, mother-father differences, and normative versus delayed childbearing. There were differences between married and cohabiting families, first- and second-time expectant parents, mothers and fathers, and between normative and delayed first-time expectant parents. For married couples to have better family dynamics than cohabiting couples is surprising for Denmark where both marriage and cohabitation are examples of a nuclear family lifestyle. A dual-path model is conceptualized as a nursing strategy to support the couples' interrelationship during their role transition. PMID- 8194941 TI - Management of non steroidal anti-inflammatory drug induced gastro-intestinal damage. PMID- 8194942 TI - The medical management of hyperlipidaemia. PMID- 8194943 TI - Guidelines on the management of chronic heart failure. PMID- 8194944 TI - ACE inhibitors in the management of hypertension. PMID- 8194945 TI - Management of endometriosis. PMID- 8194946 TI - Childhood drowning. PMID- 8194947 TI - For female cancers, is less more? PMID- 8194948 TI - Focusing on the menopause clinic. PMID- 8194949 TI - Mechanical ventilation in the elderly. PMID- 8194950 TI - Pharmacological management of angina. PMID- 8194952 TI - Use of an age related admission policy in establishing a new department of medicine for the elderly. AB - Possible admission policies when initiating new Departments of Medicine for the Elderly are discussed. We report the results of a new acute unit where an age related policy was used in an area with no prior contact with the speciality. Six hundred and fifty-one acute medical admissions aged 80 years and over were treated in the unit's first year. Average age was 84.6 years with an average stay of 8.6 days. 54% were discharged directly home with a further 17% going home after rehabilitation. Only 12% eventually needed continuing nursing care. 9.4% of the patients died. We conclude that Medicine for the Elderly is highly effective if allowed access to patients from the point of admission rather than on a take over basis. It is suggested that an age-related policy is appropriate when setting up new departments unless there is a clear indication for an alternative policy. PMID- 8194951 TI - MMR immunisation status among Dublin paediatric A&E attenders. AB - The objectives of this study were to establish the need for opportunistic MMR immunisation among paediatric A&E attenders to the three Dublin paediatric hospitals and to examine the relationship between immunisation status and socioeconomic factors. Design was that of a two month cross sectional study. Survey data was then compared with information on the Eastern Health Board (EHB) records system. Small area and multiple regression analysis of socioeconomic factors derived from participants addresses was also performed. Subjects were 337 children who attended these departments and were aged between fifteen months and five years. For 66% of cases there was a history of MMR immunisation, 30% gave a negative history and 4% did not know. Of those giving a negative history, one third said immunisation had been omitted for no specific reason. EHB records suggested that 39% were immunised, 41% were not and 20% were not on file. Eligibility for the GMS was not associated with failure to immunise. Small area and multiple regression analysis showed little association between immunisation uptake and socioeconomic factors. An opportunistic MMR immunisation policy in A&E Departments would make an important contribution to increasing overall uptake figures. Parental knowledge of the implications of measles and the effectiveness of immunisation needs to be improved. Computerised child health systems must have high data quality standards and access to these systems should be made available in A&E departments. PMID- 8194953 TI - Omeprazole treatment of chronic duodenal ulceration. AB - Omeprazole, a substituted benzimidazole, is an acid pump inhibitor, introduced for treatment of chronic duodenal ulceration. In a study of 116 patients with endoscopically documented chronic duodenal ulcers, omeprazole affected healing in 77 (66.3%) patients after two weeks and 106 (91.4%) patients after four weeks, with symptoms relief in 102 (88%) patients within the first week of treatment. There was significantly higher healing rate in females (p < 0.05) and diffuse ulceration rather than single ulcers (p < 0.05). In meta-analysis comparing omeprazole to other antiulcer drugs reported in this country, there was a significant higher healing rate (p < 0.01) and symptom relief (p < 0.01) in favour of omeprazole. It proved to be effective and safe for the short term treatment of chronic duodenal ulceration. PMID- 8194954 TI - Pain clinic attenders: an audit. AB - An audit of the first 135 referrals to a new Multidisciplinary Pain Clinic was conducted. Demographic data, pain experience and pain effects were recorded. Chronic Non-Malignant Pain was the diagnosis found most frequently. In that group, the mean duration of pain was seven years, the mean number of surgical operations was 1.95 and the mean number of medications being consumed at the time of presentation 3.5. Impaired occupational, social and recreational functioning was noted. Twice as many women were affected as men and all educational and socio economic groups were represented. Patient profiles were similar to data published on chronic pain patients attending the Mayo Clinic, Minnesota, USA. PMID- 8194955 TI - Gemeprost in the management of second trimester intrauterine fetal death. AB - Gemeprost (Cervagem), a synthetic PGE1 prostaglandin analogue was used to induce labour in 20 patients with second trimester intra uterine fetal death. The mean induction abortion interval was 13.8 hours; 17 of the 20 patients delivered within 24 hours. In 17 cases the placenta was retained and the uterus was evacuated under general anaesthesia. Nausea was noted in five (25%) patients, vomiting in two (10%) and diarrhoea in three (15%). No serious side-effects were encountered. PMID- 8194956 TI - An evaluation of a smoking prevention programme with children from disadvantaged communities. AB - This study examined the effect of a novel smoking prevention programme on children in primary schools in disadvantaged areas. The programme included integration with other school subjects as well as parental involvement and visits by Health Board personnel. Compared to matched control groups the classes in which the programme was piloted, showed less positive attitudes towards smoking and greater awareness of the dangerous consequences of smoking. The results are considered in the context of the need for approaches to smoking prevention that include both education and the restriction of access. PMID- 8194957 TI - Sleep position and SIDS in Irish infants. AB - A retrospective case-controlled study has compared the frequency of different sleeping positions in a group of 97 SIDS infants and a group of 98 control infants. The results show a clear excess of SIDS deaths among Irish infants sleeping in the prone (lying on abdomen) position with the risk of a SIDS increased 2.3 fold comparing prone to side and 10.5 fold comparing prone to back positions. Among the SIDS group 79% of infants were lying prone when found dead compared to 25% of the control group (chi square = 64.3, p < 0.001) with only 7% and 9% sleeping on their sides and backs respectively (control group 48% and 27% respectively). Irish parents should be advised to avoid placing infants in the prone position (on abdomen) to sleep as this position is associated with a significantly increased risk of the Sudden Infant Death Syndrome. PMID- 8194958 TI - Diabetes mellitus in an adult cystic fibrosis population. AB - Medical records of 132 patients attending an adult cystic fibrosis (CF) clinic were analysed to define the prevalence and clinical significance of diabetes mellitus (DM) in CF. Eighty four (63.6%) had normal blood glucose levels, 30 (22.8%) had hyperglycaemia only during intercurrent illness and 18 (13.6%) had DM. No significant differences were noted between the diabetic and non-diabetic groups for age, gender, height, weight, body mass index (BMI), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) and pancreatic supplementation. Patients with hyperglycaemia during intercurrent illness had significantly lower BMI, FEV1% and FVC% than those with normal blood glucose levels. Of the diabetics four were managed on diet, three received oral hypoglycaemic agents and eleven were insulin requiring. The prevalence of DM in CF is considerable, severity of CF does not correlate with development of overt DM, and CF patients should be screened for DM by an oral glucose tolerance test on reaching adulthood. PMID- 8194959 TI - Physiology in American women's colleges. The rise and decline of a female subculture. PMID- 8194960 TI - The Atomic Energy Commission and the politics of radiation protection, 1967-1971. PMID- 8194962 TI - Building a skill-mix team. AB - When, two years ago, both local and national advertising had failed to fill health visitor vacancies in parts of her area, Wirral locality manager Frances Wilson knew that she had to come up with some new ideas. Jane Seymour talks to health visitors and nursery nurses involved in a successful skill-mix which they say gives a better service to parents and children. PMID- 8194961 TI - Tackling infant malnutrition in The Gambia. AB - Malnutrition is common among young children in developing countries. Often it is caused by poor infant weaning practices. Karen Hoare describes a community-based infant weaning programme in The Gambia which adapted local foods to improve nutritional content. The project also resulted in the development of a simple but effective demonstration kit. PMID- 8194964 TI - Child support. What about the children? PMID- 8194963 TI - Fighting for standards. AB - HVA members have been among the most vocal and effective campaigners against cuts in community nursing services which they believe will damage services to clients. Roger Kline outlines some typical scenarios and the strategies adopted by HVA members to challenge management proposals. PMID- 8194965 TI - Positive about parenting. PMID- 8194966 TI - Building trust with local communities. PMID- 8194967 TI - Through the looking glass. PMID- 8194968 TI - Protection for pregnant women in employment. AB - October 19 is the deadline for employers to implement improvements in maternity rights laid down by the Trade Union Reform and Employment Rights Act (TURERA) and the European directive to protect pregnant women's health and safety at work. Christina Potrykus outlines what the government and, separately, the general Whitley council have in store for women employees. PMID- 8194969 TI - Returning to practice. AB - All too often health visitors seeking to return to practice following a career break are met with negative response, writes Stevie Holland. Here she recounts the words and experiences of some of the health visitors who enrolled on the HVA's open learning 'Return to practice' courses in recent years. The health visiting profession needs to encourage the enthusiasm and innovation of returners if it is to survive in today's political climate, she warns. PMID- 8194970 TI - Childcare. Paid work and domestic responsibilities. AB - Women's opportunities for paid work outside the home are constrained by their role as primary carer within the family, writes Trudy Wynne. Better childcare services should be available to women to reflect the reality of today's society in which most women are in paid employment for most of their working lives. PMID- 8194971 TI - Dental health. I. Views about preventive dental care for infants. AB - A study to investigate attitudes of health visitors and parents to preventive dental health care for young children revealed that while the majority of parents agreed early dental visits were important, few had taken their child to the dentist before the age of one year. Where dental health is poor it is vital that the health visitor continues to give parents appropriate dietary advice and to recommend early visits to the dentist, writes Elaine Bentley. PMID- 8194972 TI - Dental health. 2. Working together in dental health education. AB - Dental caries affects three quarters of five-year old children in Northern Ireland. It should be seen as a priority target for health education and health promotion initiatives, argue Grainne Quinn and Ruth Freeman. A study to investigate co-operation between health visitors and community dental officers demonstrates the importance of the frequent sharing of knowledge and expertise between the two professionals in the promotion of dental health. PMID- 8194973 TI - Helping older children grieve: a group therapy approach. AB - Many children find it hard to discuss their feelings and experiences of bereavement when a parent dies, writes Michaela Fell. Often they keep their feelings of grief to themselves, which can hinder the process of coming to terms with their loss. Here she describes how a group therapy approach can help such children. PMID- 8194974 TI - Health education for parents with special needs. AB - Working with families with communication and learning difficulties can require health visiting skills other than those taught on the formal health visitor training course, writes Val Rose. She describes how she approached the problems of one such family with a new-born baby, and the resulting design of a simple feed calculator and communication card which enabled parents and professionals to ensure the baby was being adequately nourished. PMID- 8194975 TI - Social isolation and support in pregnancy loss. AB - Drawing on the findings of a wider study, Lynda Rajan examined the social support received by women following the death of their baby through miscarriage, stillbirth or neonatal death. Her study reveals that many of the women experienced social isolation and did not receive the support they needed from partners, relatives, friends and health professionals. Sympathetic social support makes a vital contribution to the mourning process, the study showed. PMID- 8194976 TI - School health. A message for Mrs. Bottomley. AB - School nurses in the Wandsworth health district are shortly to embark on a radical re-structuring programme to introduce teamworking and boost health promotion in schools. Toni Turner reports on a revitalised school nursing service. PMID- 8194977 TI - PREP prompts cheers and fears. PMID- 8194978 TI - Community development approaches to health needs assessment. AB - Community health needs assessment has traditionally been an integral part of the health visitor's public health activities. The NHS reforms, and in particular GP fundholding, threaten this aspect of their role. Stephen Peckham and Jacqui Spanton argue that, far from restricting the health visitor's work in this area, purchasers and providers should be investing in community-based information collection, in order to obtain the data vital to provision of locality-sensitive services, and that health visitors should re-discover their role as public health advocates. PMID- 8194979 TI - Purchasing effective care for parents and young children. AB - The extension of GP fundholding and the focus on the primary health care team means that GPs have become major players in the purchasing of child and family community nursing services. Shirley Goodwin explores what effective purchasing by GP fundholders of health visiting services might entail and the principles which should inform their decisions. PMID- 8194980 TI - Facilitating parenting skills in vulnerable families. AB - Parents regularly seek advice from their health visitor about how to cope with their child's difficult behaviour. Often the health visitor feels she has nothing constructive to offer, writes Norma Angeli et al. Here they describe how one team of health visitors introduced the STEP positive parenting programme, devised in the US, successfully to help parents from all cultures, classes and backgrounds achieve a better relationship with their child. PMID- 8194981 TI - Introducing nursery nurses to the school health team. AB - Introduction of skill mix in school nursing services has tended to lag behind health visiting and district nursing, where its implementation has met with very mixed responses. Elizabeth Lochhead describes a skill mix review in the East Dorset school nursing service which introduced nursery nurses to work alongside school nursing sisters in providing a health assessment and health promotion service to local schools. PMID- 8194982 TI - School entry screening by the school nurse. AB - To replace the conventional school medical, a new system of screening school entrants by the school nurse was introduced in the Canterbury and Thanet health district, writes Pauline Bolton. The system has been shown to be satisfactory for the children and their parents, to increase the school nurse's job satisfaction and to free up clinical medical officer time for tasks requiring specifically medical skills. It is also more cost-effective. PMID- 8194983 TI - Head to toe school health. AB - Margaret Green and Karen Moss describe how they and the staff at one primary school together devised a month-long programme of health promotion events to encourage children to think positively and responsibly about their health and safety. The project involved colleagues from the health services as well as from other agencies and organisations, to demonstrate the breadth of issues involved in maintaining good health. PMID- 8194984 TI - Sex education matters. PMID- 8194985 TI - Disciplinary procedures. Cautionary tales. AB - HVA local accredited representatives are reporting an increase in disciplinary cases against field staff. Disciplinary cases can be very stressful for all concerned. They should not be used unless clearly appropriate, as Roger Kline explains. PMID- 8194986 TI - Child maintenance. Matthew lives with Jenny and Mark. PMID- 8194987 TI - Pulling the strings of world food trade. PMID- 8194989 TI - Something to think about. PMID- 8194988 TI - Protecting the AIDS patient's right to make treatment decisions. PMID- 8194990 TI - Planning home care services for people living with AIDS. AB - As the number of individuals infected with the human immunodeficiency virus (HIV) increases, so does the demand for healthcare services. The debilitating manifestations seen in the later stages of illness, in association with the diagnosis of acquired immune deficiency syndrome (AIDS), often require the assistance of home care providers. Establishing a database of information, not only on the clinical needs of individuals but also on person-specific details, is essential to identify the nursing care needs of this population. The delivery of home care services to people living with AIDS (PLWA) includes the client, the significant other(s), and the community in which the client resides. PMID- 8194991 TI - Protocol for nursing assessment and management of stomatitis. AB - The purpose of this paper is to establish comprehensive criteria for identification and management of clients at risk for stomatitis. Assessment of the high-risk client may provide early detection, thereby reducing the potential for progressive severity of stomatitis. PMID- 8194992 TI - Nutritional status: a basic 'vital sign'. AB - The purpose of this article is to alert and inform the home healthcare nurse about the national focus on the unacceptably high levels of malnutrition in the elderly; its significance in patient outcome; the effort of the Nutrition Screening Initiative to help all healthcare professionals incorporate routine nutrition screening and intervention activities into healthcare practice; and the simple screening tools available to assist in evaluations. PMID- 8194993 TI - Nutrition interventions for the HIV positive client. AB - Several factors contribute to malnutrition during HIV infection. These factors can be grouped into three categories: hypermetabolism, inadequate intake, and malabsorption. This article presents a brief overview of these categories and offers suggestions to help the home healthcare nurse manage nutritional interferences. Useful resources are also included. PMID- 8194994 TI - Home care of a malnourished AIDS client. AB - Many HIV positive clients experience malnutrition that may decrease the quality and length of life. The case study in this article includes study questions that provide the home healthcare nurse an opportunity to plan interventions that may increase nutrient intake. PMID- 8194995 TI - Cataracts: at any age. AB - More than 330,000 cataract surgeries are performed annually in the United States. Senile cataracts account for more than 75% of all cataracts. Most are done without complications, yet I was younger than 40 years of age and had multiple complications related to surgery. PMID- 8194996 TI - Medicare update: criteria for reimbursement for pronouncement of death visits by registered nurses, and revisions to the state operations manual. PMID- 8194997 TI - Conceptual framework for nursing practice in the home: the Rice model of dynamic self-determination. PMID- 8194998 TI - Hospice nursing and the AIDS epidemic. PMID- 8194999 TI - Implementation of a hepatitis B vaccine program: a how-to guide for home care providers. PMID- 8195000 TI - Chronic sorrow in multiple sclerosis: a case study. PMID- 8195001 TI - Sharing: goodbye and thank you Mrs. P. PMID- 8195003 TI - Stand up and be counted. PMID- 8195002 TI - Universal precautions do not equal infection control: preentry-level education for nurses must include infection control. An issue for change. PMID- 8195004 TI - Hb Poitiers [alpha 45(CE3)His-->Asp]: a new hemoglobin variant with a two-fold increase in oxygen affinity. AB - Hb Poitiers or alpha 45(CE3)His-->Asp was found in a 9-year-old French Caucasian boy. The structural modification concerns a heme contact and is responsible for an increased oxygen affinity and a faster than normal rate of autooxidation. PMID- 8195005 TI - Hb Kurdistan [alpha 47(CE5)Asp-->Tyr], a new alpha chain variant in combination with beta (0)-thalassemia. AB - We have characterized the structural abnormality of a new alpha chain mutant found in a Kurdish family. The clinical and hematological investigation of eight individuals have shown that the alpha variant is associated with a beta(0) thalassemia mutation (nonsense codon 39). The tryptic peptide map and sequencing of the abnormal peptide revealed the substitution of an aspartic acid by a tyrosine residue at position 47 of the alpha chain; furthermore, selective amplification and molecular analysis of both alpha genes have assigned the new mutation to the alpha 2 gene. The variant, named Hb Kurdistan, is clinically silent but the percentage of this hemoglobin found in the only double heterozygote for beta (0)-thalassemia and alpha-Kurdistan, presumably indicates a lower affinity of the abnormal chain for the beta polypeptides. PMID- 8195006 TI - Hb Footscray or alpha 133(H16) Ser-->Arg: a new hemoglobin variant. AB - Hb Footscray, alpha 133(H16) Ser-->Arg, is a newly described hemoglobin variant found in an adult male of Polish-Hungarian descent. Hematological data and stability by the isopropanol stability test were normal. The abnormal hemoglobin comprised 15% of total hemoglobin and migrated as a split band in the Hb F position on cellulose acetate at pH 8.6. Like Hb Manitoba, which is also a Ser- >Arg mutation and occurs in a very similar spatial position, the split bands presumably arise from the formation of asymmetric hybrids between Hb Footscray and Hb A. PMID- 8195007 TI - Hemoglobin variants in North Africa. AB - The populations of Morocco, Algeria, and Tunisia are composed of different ethnic groups including Arabs, Berbers, Sub-Saharan Africans, Europeans, and Turks. Between 1981 and 1991, we studied more than 3,000 individuals from these North African countries. One-hundred and eighty-one carried one (or more) unusual hemoglobin variant(s) other than Hb S and Hb C which are the most frequent variants in these countries. Each of these 181 individuals was heterozygous for at least one of the 49 abnormal alpha or beta alleles identified by electrophoretic and/or structural studies, and some homozygotes were detected. A few mutants are common in North Africa: Hb O-Arab, Hb D-Punjab and Hb G Philadelphia. Other mutants encountered in European or African populations are found in relatively few North African families. The observed polymorphisms in the populations of North Africa probably result largely from their complex ethnic origins. PMID- 8195008 TI - Hb G-Waimanalo [alpha 64(E13)Asp-->Asn] observed in a Caucasian family. PMID- 8195009 TI - Hb Capa or alpha (2)94(G1)Asp-->Gly beta 2, a mildly unstable variant with an A- >G (GAC-->GGC) mutation in codon 94 of the alpha 1-globin gene. PMID- 8195010 TI - Hb D-Iran [beta 22(B4)Glu-->Gln] in southern Italy. PMID- 8195011 TI - Alpha 2-globin gene mutation Hb G-Waimanalo: occurrence in combination with alpha thalassemia-1. PMID- 8195012 TI - Bioreductive drugs for cancer therapy: the search for tumor specificity. AB - The activity of three different classes of bioreductive drug, i.e., heterocyclic nitro compounds, N-oxides and quinones are compared. The major characteristics of RB-6145, tirapazamine and E09 are summarized and future directions for development of new bioreductive drugs are outlined. The concept of potentiating bioreductive drug activity by increasing tumor hypoxia is described and illustrated in particular by the use of photodynamic therapy (PDT) in combination with RSU-1069. Examples of how the therapeutic effectiveness of this approach can be studied by the use of 31P magnetic resonance spectroscopy is described. The effects of manipulation of nitric oxide (NO) levels in tumors by the use of modifiers of NO-synthase activity is illustrated by studies with the inhibitor nitro-L-arginine in experimental tumors. Associated changes in tumor physiology indicate promise for potential applications in therapy. Finally, changes in expression of reductase enzyme levels are considered in the context of the heterogenous nature of the tumor microenvironment. PMID- 8195013 TI - The radiosensitivity of quiescent cell populations in murine solid tumors in irradiation with fast neutrons. AB - PURPOSE: We analyzed the characteristics of radiosensitivity and potentially lethal damage repair in the quiescent cell populations of murine SCC VII solid tumors irradiated with fast neutrons, in comparison with those irradiated with 10 MV X rays. METHODS AND MATERIALS: SCC VII tumor-bearing C3H/He mice were irradiated with 30 MeV fast neutrons or 10 MV X rays after receiving 10 injections of 5-bromo-2'-deoxyuridine (BUdR) to label all proliferating tumor cells. Immediately or 24 h after irradiation, the tumors were excised and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus frequency in cells without BUdR labeling was determined using immunofluorescence staining to BUdR. This micronucleus frequency was then used to calculate the surviving fraction of unlabeled cells from the regression line for the relation between micronucleus frequency and the surviving fraction of all tumor cells. Thus, a cell survival curve could be determined for the cells not labeled by BUdR, which can be regarded as the quiescent cells for all practical purposes. RESULTS: The difference in intrinsic radiosensitivity between all tumor and quiescent cells became smaller by using fast neutrons, compared with X rays, especially when large radiation doses were given. Potentially lethal damage repair by quiescent cells was less evident following irradiation with fast neutrons than with X rays, especially when large doses were delivered. CONCLUSION: By using fast neutrons in clinical radiotherapy, the radiosensitivity of solid tumors is thought to depend on their heterogeneity less critically than for X rays. PMID- 8195014 TI - The interaction of epidermal growth factor and radiation in human head and neck squamous cell carcinoma cell lines with vastly different radiosensitivities. AB - PURPOSE: This study was performed to characterize the interaction of epidermal growth factor and radiation in two human head and neck squamous cell cancer cell lines of vastly different radiosensitivities (UM-SCC-6 Radiosensitive; UM-SCC-1 radioresistant). METHODS AND MATERIALS: The two human head and neck squamous cell cancers (UM-SCC-1 and UM-SCC-6) were grown in medium and following the appropriate treatments, cell survival was assessed by a standard colony formation assay. Growth inhibition was assessed by monitoring cell counts following treatment and flow cytometry was used to assess cell cycle distributions. RESULTS AND CONCLUSION: It was determined that exposure to epidermal growth factor (10 ng/ml) for 24 h prior to radiation resulted in radiosensitization in both cell lines, however, the magnitude of radiosensitization was greater in the radiosensitive UM-SCC-6 cells compared to the radioresistant UM-SCC-1 cells. Treatment of the UM-SCC-6 cells with epidermal growth factor (EGF) (10 ng/ml) for 24 h resulted in a growth delay, however, cell growth returned to normal approximately 24 h following removal of EGF. Similar treatment of the UM-SCC-1 cells resulted in no growth inhibition. The 24 h pre-radiation exposures to EGF (10 ng/ml) did not affect the radiation-induced growth delay in either cell line. Additionally, the 24 h exposures to EGF (10 ng/ml) did not affect the radiation induced growth delay in either cell line. Additionally, the 24 h exposures to EGF (10 ng/ml) did not cause the cells to enter a more radiosensitive cell cycle phase. Further work will be necessary to determine whether events associated with the EGF-induced growth delay in the UM-SCC-6 cells are associated with the enhanced EGF-induced radiosensitization in these cells compared to UM-SCC-1 cells. PMID- 8195015 TI - Novel concepts in modification of radiation sensitivity. AB - PURPOSE: To determine whether biological effects of radiation, such as apoptosis, that differ from classical clonogenic cell killing, can be modified with agents that would not be expected to modify classical clonogenic cell killing. This would expand the range of potential modifiers of radiation therapy. METHODS AND MATERIALS: EL4 murine lymphoma cell apoptosis was determined by electrophoretic analysis of deoxyribonucleic acid (DNA) fragmentation. DNA was extracted 24 h after irradiation or addition of inducing agents. Modifiers of radiation-induced apoptosis were added immediately after irradiation. The effects of radiation on wounded endothelial monolayers were studied by scraping a line across the monolayer 30 min after irradiation. Cell detachment was used as an endpoint to determine the protective effect of prolonged exposure to retinol prior to irradiation. RESULTS: EL4 cell apoptosis can be induced by tert-butyl hydroperoxide or the glutathione oxidant SR-4077. Radiation-induced EL4 cell apoptosis can be inhibited with 3-aminobenzamide, an agent that sensitizes cells to classical clonogenic cell killing. Radiation-induced endothelial cell detachment from confluent monolayers can be modified by pretreatment with retinol. CONCLUSION: These results raise the possibility that radiation could induce apoptosis by an oxidative stress mechanism that is different from that involved in classical clonogenic cell killing. These and other recent findings encourage the notion that differential modification of classical clonogenic cell killing and other important endpoints of radiation action may be possible. PMID- 8195016 TI - Repair of potentially lethal radiation damage in human squamous carcinoma cells after chronic hypoxia. AB - PURPOSE: To examine the repair of radiation induced potentially lethal damage in A431 and CaSki cells after chronic hypoxia. METHODS AND MATERIALS: Cells in exponential phase are subjected to hypoxia (< 10 ppm oxygen) for up to 12 h and then are allowed to re-oxygenate in air for up to 4 h. Cells are then irradiated with gamma rays. Cell survivals are measured by clonogenic assay immediately and at different times after irradiation. RESULTS: Compared to aerobic controls, an increase in the level of potentially lethal damage repair (PLDR) is demonstrated in A431 cells reoxygenated for 10 min after > 4 h of hypoxia. The repair returned to aerobic control level by 3 h of reoxygenation. PLDR of A431 cells reached maximum at about 9 h after irradiation in cells reoxygenated for 10 min after hypoxia. However, the repair is maximum at 6 h in cells reoxygenated for 3 h after hypoxia and in aerobic cells not previously exposed to hypoxia. Reoxygenation after chronic hypoxia did not affect the PLDR capacity and repair kinetics of CaSki cells. CONCLUSION: The results suggest that radiosensitization by reoxygenation after chronic hypoxia is not related to inhibition of PLDR. PMID- 8195017 TI - Activators of protein kinase C selectively mediate cellular cytotoxicity to hypoxic cells and not aerobic cells. AB - PURPOSE: By understanding the signal transduction pathways through which a cell responds to changes in environmental oxygen levels, we may be able to therapeutically exploit this response by manipulating these pathways. MATERIALS AND METHODS: The human adenocarcinoma cell line A549 was exposed to varying durations of hypoxia alone and then plated for survival, or treated with PKC activating agents for 1 h before plating for survival. Western blots were used to determine the kinetics of PKC epsilon and phospholipase C induction. RESULTS: The level of hypoxic killing was directly related to the time of exposure and inversely related to the level of oxygen in the environment. Exposure of the cells to protein kinase C (PKC) activators for 1 h after chronic hypoxic exposure increased cell killing by at least an additional three logs beyond that found for hypoxia alone. Treatment of cells with an inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate (PDA) resulted in no increase in hypoxic cell killing, even at the highest concentrations of PDA which produced no detectable toxicity under normal aerobic conditions. Using inhibitors of phospholipases A2 and C, we were able to completely inhibit the additional hypoxic cell killing induced by TPA, but not the uninduced hypoxic cell killing. CONCLUSION: These studies suggest that accumulation of phospholipid breakdown products may be responsible for TPA induced cell killing, and that hypoxic cells differ from aerobic cells in their ability to tolerate these products. PMID- 8195018 TI - Misoprostol-induced radioprotection of oncogenic transformation. AB - PURPOSE: Prostaglandins are associated with a variety of both pathologic and normal physiological effects in mammals. Among this broad array of effects, prostaglandins have been shown to provide protection to tissues from a variety of injurious agents including ionizing radiation. Of the prostaglandins tested to date, an analogue of prostaglandin E1, misoprostol (cytotec) was found to be a very effective radioprotector. The purpose of this study was to assess the ability of misoprostol to protect cells from the cytotoxic and oncogenic effects of ionizing radiation. METHODS AND MATERIALS: Pregnant Syrian hamsters were injected subcutaneously with 125 micrograms misoprostol/100 g body weight 2 h before being exposed to graded doses of X rays. Embryos were excised immediately after irradiation and cells were explanted into culture dishes. Following 14 days of incubation, cells were fixed in formalin and stained with giemsa for examination of cell clonogenicity and morphological transformation. RESULTS: First, misoprostol protected cells from some degree of radiation toxicity. A reduction in cell killing by a factor of 1.5 was seen at 10% cell survival. Second, based on transformation studies, a higher frequency of oncogenic transformation is seen for cells exposed in utero to graded doses of X rays alone than for cells exposed to the combination of misoprostol followed by radiation. In the presence of misoprostol, transformation is reduced by a factor of 20 at the level of 10(-3) transformants per surviving cell. CONCLUSION: Misoprostol may have clinical utility, not only in protecting selected normal tissues during cancer therapy, but it may also be useful in protecting cells from secondary tumors caused by ionizing radiation. PMID- 8195019 TI - Expression of xenobiotic-metabolizing enzymes by primary and secondary hepatic tumors in man. AB - PURPOSE: To determine the immunohistochemical expression of xenobiotic metabolising enzymes (XME) in normal livers, primary hepatocellular carcinomas (hepatomas) and secondary hepatic tumors from colonic primary tumors. METHODS AND MATERIALS: The expression of XME in primary (n = 16) and secondary (n = 21) hepatic tumors and patients with no malignancies (n = 20) were investigated using polyclonal antibodies raised against the following rat enzymes CYP1A1, CYP2B1, CYP2C6, CYP3A1, CYP4A1, cytochrome P-450 reductase, epoxide hydrolase and testosterone UDP-glucuronyl transferase. The rat cytochrome P-450 antibodies recognize various human isoenzymes within the same gene family. Immunohistochemistry was undertaken using the immunoperoxidase and alkaline phosphatase anti-alkaline phosphatase techniques. RESULTS: There was a reduction in the overall expression of all XME by tumor tissue compared to adjacent nonneoplastic liver cells (p = 0.008), more in livers with secondary tumors (p < 0.0001) and reduced expression of XME by hepatomas and secondary liver tumors compared to livers with no malignancy. A tendency for higher expression of all XME by nonneoplastic liver cells from patients with hepatomas relative to nonmalignant livers was observed, with significantly higher expression of CYP3A4/5 and testosterone UDP-GT enzymes (odds ratio 3.12; CI 1.59-6.10). CONCLUSION: The expression of XME by tumor tissue is reduced in primary and secondary hepatic malignancies. The expression of XME by nonneoplastic liver cells is higher in patients with hepatomas than patients with no hepatic malignancies. These alterations in XME activities may have important therapeutic implications in the response and toxicity to systemic anti-cancer therapy, due to altered pharmacokinetics. In addition, differential expression of these enzymes by normal and malignant cells may be important for the rational design of selective anti-tumor drugs. PMID- 8195020 TI - 31P MRS to monitor the induction of tumor hypoxia by the modification of the oxygen affinity of hemoglobin using BW 589C. AB - PURPOSE: BW 589C induces severe tumor hypoxia by modifying the affinity of oxyhemoglobin, causing a left shift of the oxygen-hemoglobin dissociation curve. 31P magnetic resonance spectra (MRS) was used to monitor the effects of BW 589C on tumor energy metabolism in three experimental tumor models. METHODS AND MATERIALS: HT-29 colon xenograft, murine transplantable RIF-1 fibrosarcoma and KHT sarcoma were studied in unanesthetised mice. 31P MR spectra were acquired on a 4.7 Tesla magnet before administering oral BW 589C (250 mg/kg) and after 3, 6, and 24 h. Samples of tail vein blood were then taken for 2,3 DPG levels for RIF-1 and HT-29 tumors. RESULTS: Doubling of inorganic phosphorus (Pi) to total phosphorus was observed 5-6 h after BW 589C for all three tumor types. Although the left shift due to BW 589C persists at 24 h, the level of Pi to total phosphorus returned to baseline with no significant difference from control values for the RIF-1 and HT-29 tumors. These results suggest that there was cellular metabolic adaptation to the reduction of oxygen delivery by BW 589C. This does not appear to involve 2,3 DPG as there was no significant alteration in tumor levels. The death of hypoxic cells may, also, have contributed to the recovery of Pi to total phosphorus. CONCLUSION: The efficacy of bioreductive drugs can be enhanced by increasing the severity of tumor hypoxia. 31P MRS in conjunction with other techniques for assessing the intratumor environment could play an important role in planning cancer therapy. PMID- 8195022 TI - Relative importance of DT-diaphorase and hypoxia in the bioactivation of EO9 by human lung tumor cell lines. AB - PURPOSE: Although a number of bioreductive agents are substrates for purified DT diaphorase the role of this enzyme in either activation or detoxification of these agents in the whole cell is unclear. The aim of this study was to determine the role of DT-diaphorase in the metabolic activation of EO9 under both aerobic and hypoxic conditions. METHODS AND MATERIALS: A panel of lung cancer cell lines was used and drug sensitivity was determined by clonogenic or tetrazolium-dye based assays. Activities of DT-diaphorase, cytochrome P450 and cytochrome b5 reductase were determined spectrophotometrically by following the reduction of cytochrome c. RESULTS: Small-cell lung cancer cell lines showed a 600-fold range in DT-diaphorase activities but levels were much higher in three of the four non small-cell lines. Activities of cytochromes P450 and b5 reductase were much lower than those of DT-diaphorase and showed much less variation between cell lines. There was no relationship between the activities of any of the enzymes and aerobic sensitivity to SR 4233, BCNU and cis-platin. Under aerobic conditions there was a clear correlation between DT-diaphorase activity and sensitivity to EO9. The small-cell lines were much more resistant to EO9 than the DT-diaphorase rich non-small-cell lines. A doxorubicin resistant variant of one of the small cell lines (H69LX10) did not show cross resistance to EO9 but did show a small degree (3-fold) of cross resistance to SR 4233. Under hypoxic conditions, cell lines with high levels of DT-diaphorase showed only a small increase in sensitivity to EO9 (1.5-7 fold); cell lines with low levels of activity showed a 10-37-fold increase in sensitivity. CONCLUSION: These results suggest that under hypoxic conditions, EO9 is metabolized by 1-electron reducing enzymes to a toxic species. This reduction product is oxygen sensitive but a similar degree of activation is obtained under aerobic conditions in cell lines with high levels of 2-electron reducing DT-diaphorase. PMID- 8195021 TI - Modification of the aerobic cytotoxicity of etanidazole. AB - PURPOSE: To determine the feasibility of modifying the aerobic cytotoxicity of etanidazole without interfering with the tumoricidal action of radiation plus etanidazole. METHODS AND MATERIALS: The aerobic cytotoxicity of etanidazole was studied using two different models: (1) Induction of apoptosis in EL4 cells: apoptotic DNA fragmentation was analyzed by agarose gel electrophoresis following 24 h treatment with etanidazole alone or in combination with various modifiers. (2) Spinal cord neuronal loss in organotypic roller tube cultures: Survival of acetylcholinesterase positive ventral horn neurons was analyzed morphometrically following 72 h treatment with etanidazole alone or in combination with vitamin E succinate. RESULTS: Etanidazole (10 mM) induced apoptosis in EL4 cells. This effect was suppressed by 24 h treatment with TPA, IBMX, the free radical scavenger TEMPOL or vitamin E succinate. Vitamin E succinate also protected spinal cord cultures from etanidazole-induced neuronal loss. CONCLUSION: These results suggest that it might be possible to modify the neurotoxicity of etanidazole with agents that would not be expected to interfere with the tumoricidal action of radiation plus etanidazole. PMID- 8195023 TI - In vitro cytotoxicity and chemosensitizing activity of the dual function nitroimidazole RB 6145. AB - PURPOSE: To determine the cytotoxicity and chemosensitizing potential of RG 6145 in mouse KHT/iv and human A549 tumor cells. METHODS AND MATERIALS: RSU 1069, the lead compound in a series of nitroimidazoles containing an alkylating aziridine function, has been shown to possess a high degree of selective cytotoxicity for hypoxic cells in addition to being a potent sensitizer of radiation and chemotherapy. Unfortunately, preliminary clinical studies have revealed a dose limiting gastrointestinal toxicity for RSU 1069. Recently RB 6145, the ring opened analogue of RSU 1069, has been found to be less emetic than RSU 1069. In the present studies, we assessed both the differential hypoxic cell cytotoxicity of RB 6145 and its chemosensitizing potential when combined concomitantly with variable doses of the activated form of cyclophosphamide (4-hydroperoxy cyclophosphamide, 4-OOH-CP) or the nitrosourea CCNU. RESULTS: As we had observed previously for RSU 1069, RB 6145 was found to be less cytotoxic to human than rodent tumor cells. In addition, the degree of selective cytotoxicity toward hypoxic cells was (a) less in A549 than in KHT/iv cells (factor of 9 vs. 80) but (b) comparable to that seen with RSU 1069. For both cell lines, inclusion of the sensitizer enhanced the cell killing of the chemotherapeutic agent 4-OOH-CP by a factor of approximately 1.5-1.7-fold. When combined with CCNU, RB 6145 increased the killing of A549 cells approximately 1.8-fold. Similar hypoxic cell preferential cytotoxicity and enhancement in anti-tumor treatment efficacy were seen when A549 cells were exposed to the R enantiomer of RB 6145 (PD 144872) either alone or in combination with CCNU. CONCLUSION: These data support the notion that further consideration should be given to the clinical application of these bioreductive agents. PMID- 8195024 TI - The reactivity of chloramphenicol reduction products with DNA bases. AB - PURPOSE: The interaction between the constituent bases of deoxyribonucleic acid and the reduction products of the nitro-aromatic compound chloramphenicol and its nitroso derivative have been studied using an electrochemical system. METHODS AND MATERIALS: The changes to the voltammetry of chloramphenicol and nitrosochloramphenicol upon addition of adenine, cytosine, guanine, and thymine at various concentrations have been measured. The biological implications of reductive activation of both chloramphenicol and nitrosochloramphenicol were examined using a phi X174 double transfection technique which measures biologically relevant deoxyribonucleic acid damage. RESULTS: Measurement of the voltammetric response of chloramphenicol shows that the most noticeable change upon base addition is a decrease in the lifetime of the nitro radical anion in the following order of decreasing activity: adenine, thymine, and cytosine. No effect was observed with guanine. The reversible 2-electron nitrosochloramphenicol-hydroxychloramphenicol couple showed no interaction on the voltammetric timescale, although binding of the hydroxylamine to guanine was observed. Interaction of the azo derivative, formed as a consequence of further reduction plus chemical reaction of nitrosochloramphenicol was observed. Biological studies showed that no significant effect on deoxyribonucleic acid by chloramphenicol or nitrosochloramphenicol was observed under oxic conditions. Controlled reduction of nitrosochloramphenicol to the hydroxylamine gave considerably less damage than when nitrosochloramphenicol or chloramphenicol was completely reduced. CONCLUSION: The chloramphenicol nitro radical anion reacts selectively with the bases of deoxyribonucleic acid. Reduction products of nitrosochloramphenicol beyond the 2-electron hydroxylamine are highly reactive to deoxyribonucleic acid. PMID- 8195025 TI - Does DNA targeting affect the cytotoxicity and cell uptake of basic nitroquinoline bioreductive drugs? AB - PURPOSE: A series of 4-(N,N-dimethylaminopropylamino)-5-nitroquinoline bioreductive drugs was studied to determine whether DNA binding influences cytotoxic potency, hypoxic selectivity or cellular uptake in cell culture. METHODS AND MATERIALS: Cytotoxicity was assessed by clonogenic assay of stirred suspension cultures of aerobic (20% O2) or hypoxic (< 10 ppm O2) late log-phase AA8 cells. Drug uptake was measured by high performance liquid chromatography of acetonitrile-extracted cell pellets and extracellular medium, or by using radiolabelled drug. Drug binding to calf-thymus DNA was measured by equilibrium dialysis. Intracellular pH was determined using the [14C]-5,5-dimethyl-2,4 oxazolidinedione method and intralysosomal pH using the fluorescein isothiocyanate-labelled dextran method. RESULT: The compounds were weak DNA binders under physiological conditions, with association constants in the range 25-480 M-1. There was no correlation between DNA binding affinity and hypoxic or aerobic cytotoxic potency, or hypoxic selectivity. These compounds were accumulated by cells to high concentrations (25-60 fold higher than extracellular), but cell uptake also showed no relationship to DNA binding affinity. Ammonium chloride selectively raised intralysosomal pH and inhibited the cellular accumulation of these drugs. CONCLUSION: These results indicate that DNA binding is not the major determinant of cytotoxic potency, hypoxic selectivity, or cellular uptake of the 5-nitroquinolines. Instead, the variable contribution of a nonbioreductive mechanism of toxicity appears to underlie the differences in cytotoxic potency and hypoxic selectivity within this series. The high intracellular drug concentrations of these diprotic bases appear to be due primarily to lysosomal uptake rather than DNA binding. Lysosomal uptake might restrict diffusion of basic bioreductive drugs to the target hypoxic regions of solid tumors. PMID- 8195026 TI - Nitrobenzyl mustard quaternary salts: a new class of hypoxia-selective cytotoxins capable of releasing diffusible cytotoxins on bioreduction. AB - PURPOSE: To explore the utility of a new class of compounds, nitrobenzyl mustard quaternary salts, as hypoxia-selective prodrugs of diffusible cytotoxins. METHODS AND MATERIALS: The parent compound N,N-bis(2-chloroethyl)-N-methyl-N-(2 nitrobenzyl)ammonium chloride (SN 25246) was prepared by reaction of 2 nitrobenzyl chloride with N-methyldiethanolamine, and reaction of the resulting quaternary diol with thionyl chloride at room temperature. The rate of release of mechlorethamine from this compound in the presence of cells under aerobic and hypoxic conditions was determined by trapping with diethyldithiocarbamate. Cytotoxicity was assessed by clonogenic assay of stirred suspension cultures of EMT6 cells, and also in intact and dissociated EMT6 spheroids. In vivo activity was evaluated in mice bearing SC KHT tumors. RESULTS: The parent compound is a stable, water-soluble compound with an E(1) of -369 mV. It releases mechlorethamine, and shows selective toxicity towards hypoxic EMT6 cells in culture, increasing with time to several 1000-fold after 4 h. It is much more active against intact than dissociated EMT6 spheroids, and shows low but statistically significant activity against KHT tumors in vivo. CONCLUSION: Nitrobenzyl mustard quaternary salts are a new class of hypoxia-selective cytotoxin. The parent compound shows very high selectivity for hypoxic cells in vitro, and undergoes reduction in hypoxic cells, releasing mechlorethamine which can back-diffuse to kill surrounding oxygenated cells. PMID- 8195027 TI - Exploiting tumor hypoxia through bioreductive release of diffusible cytotoxins: the cobalt(III)-nitrogen mustard complex SN 24771. AB - PURPOSE: To assess the oxygen dependence of a novel cobalt-nitrogen mustard complex, SN 24771, designed to release a diffusible cytotoxic metabolite in hypoxic tumor microenvironments. METHODS AND MATERIALS: Oxygen dependence of cell killing was assessing in well-stirred single cell suspensions obtained by enzymatic dissociation of EMT6 spheroids, using a sensitive oxygen electrode to measure oxygen concentrations in solution. Cell killing in intact EMT6 spheroids was also compared with that in single cell suspensions. RESULTS: Cytotoxicity of SN 24771 in single cell suspensions was inhibited by very low concentrations of oxygen. The C50 value (O2 required for 50% inhibition of log cell kill) was ca. 0.02% O2 at 1 h, and the K value (O2 required to give a cytotoxic potency equal to the average of that at zero and infinite O2) was of a similar order. However, intact spheroids were much more sensitive to SN 24771 than could be accounted for by the K curve for single cell suspensions, this estimate being based on published data for the oxygen concentration profile in these spheroids. CONCLUSION: The cytotoxicity of SN 24771 is inhibited appreciably at oxygen concentrations which are too low to provide radiosensitization. In this respect, SN 24771 resembles organic bioreductive drugs such as quinones and nitroaromatic compounds. However, the extensive killing observed in multicellular spheroids is consistent with release of a diffusible nitrogen mustard on reduction. Bioreductive drugs with a low K value for activation, but which release a diffusible cytotoxin, may have desirable properties as tumor radiosensitizers. PMID- 8195028 TI - Comparing the anti-tumor effect of several bioreductive drugs when used in combination with photodynamic therapy (PDT). AB - PURPOSE: To compare the effect on the RIF-1 murine sarcoma of nine bioreductive agents from five different classes when used in combination with either photodynamic therapy or clamping. METHODS AND MATERIALS: RIF-1 tumors implanted intradermally in C3H mice were treated with either 50J photodynamic therapy or with 120 min clamping in combination with either misonidazole, pimonidazole, metronidazole, nimorazole, RB6145, RSU1069, SR4233, mitomycin-C, or RB90740. The tumors were measured 3 times-per-week until reaching 4 x their initial treatment volume. RESULTS: RSU1069 produced the greatest anti-tumor activity in combination with both photodynamic therapy and clamping. RB6145 also substantially enhanced the effect of photodynamic therapy and clamping whereas misonidazole induced a smaller, but significant increase. Mitomycin-C had no effect under clamped conditions, but greatly increased the tumorcidal effect of photodynamic therapy. Mitomycin-C also induced an effect when given with light alone. None of the other agents showed any augmentation of the tumor cell killing induced by photodynamic therapy. CONCLUSION: Of the bioreductive agents studied RSU1069, RB6145 and mitomycin-C showed the greatest anti-tumor response in combination with photodynamic therapy. PMID- 8195029 TI - Radiolytic and photochemical reduction of the hypoxic cytotoxin 1,2-dihydro-8-(4 methylpiperazinyl)-4-phenylimidazo [1,2-a] pyrido [3,2-e] pyrazine 5-oxide (RB90740) and a potential mechanism for hypoxia-selective toxicity. AB - PURPOSE: To study the reduction of RB90740 (1), a fused pyrazine mono-N-oxide that has an oxic:hypoxic cytotoxicity ratio of > 10 in a range of murine and human tumor cells in vitro. METHODS AND MATERIALS: Reduction of 1 has been initiated radiolytically and photochemically in aqueous solution and the products isolated and characterized by high performance liquid chromatography (HPLC). RESULTS: Radiolytic reduction of 1 leads to the formation of the 2-electron reduced product, 2. The stoichiometry of the reduction is pH dependent, increasing from 1 to 2 with increasing pH, but independent of the presence of formate or 2-methyl 2-propanol in the reduction mixture. A dimerization product, 3, is also found, which is produced in greater yields at lower pH (< 6). Photochemical reduction of 1 to 2 was also found to be facile. Photolysis of 1 also leads to a deoxyribonucleic acid cleavage reaction. CONCLUSION: Since 2 is not cytotoxic towards hypoxic cells at concentrations at which 1 is toxic, a probable candidate as the cytotoxic species under hypoxic conditions is the 1 electron reduced intermediate species. PMID- 8195030 TI - Pharmacokinetics, metabolism and distribution of 1,2-dihydro-8-(4 methylpiperazinyl)-4-phenylimidazo [1,2-A] pyrido [3,2-E] pyrazine-5-oxide in C3H mice. AB - PURPOSE: 1,2-Dihydro-8-(4-methylpiperazinyl)-4-phenylimidazo [1,2-a] pyrido [3,2 e] pyrazine-5-oxide (RB90740) is a bioreductive drug with an oxic to hypoxic toxicity ratio of 16 in cultured V79 cells in vitro. The aim of this study was to examine the pharmacokinetics, metabolism and distribution of the drug in tumor bearing C3H mice. METHODS AND MATERIALS: A high pressure liquid chromatography assay for the quantitative determination of concentrations of the drug and its metabolites has been developed and used to examine their distribution in blood, RIF-1 and KHT tumors, brain, muscle, and liver tissue. Urine and feces collected for 24 h after drug administration have been examined for the drug and its metabolism products. RESULTS: Three metabolites, two of which have been identified, have been observed in mouse tissue. 1,2-Dihydro-8-(4 methylpiperazinyl)-4-phenylimidazo [1,2-a]pyrido[3,2-e]pyrazine (RB92815) is the two-electron reduced species, which is observed in liver, urine and occassionally in tumor samples. 1,2-dihydro-8-(4-piperazinyl)-4-phenylimidazo [1,2-a]pyrido[3,2 e]pyrazine-5-oxide (RB1739), the N-demethylated compound, is observed in urine and liver. Elimination of the drug after an intraperitoneal dose of 50 mg/kg is biphasic with t(1)2 alpha = 3 min and t(1)2 beta = 219 min. The area under the curve for blood concentration vs. time is 1.4 mg ml min-1. The drug is preferentially taken up into tumor tissue as is apparent from the area under the curve values for RIF-1 (28.3 mg ml min-1) and KHT (18.4 mg ml min-1) tumors. CONCLUSION: From these values of the area under the curve it is suggested that the drug is present in tumor tissue at concentrations sufficient to eliminate the hypoxic fraction provided reduction to a toxic species occurs. Bioreduction by the addition of two electrons to form RB92815 occurs in some tumors, but it is not known if this is due to an obligate two-electron detoxifying step or if reduction occurs by single electron additions via a toxic free radical species. PMID- 8195031 TI - Enhanced radiation-sensitivity by preincubation with nitroimidazoles: effect of glutathione depletion. AB - PURPOSE: The mechanism of enhanced radiosensitization by nitroheterocyclics after a preincubation period under hypoxic conditions was investigated. The hypothesis that this phenomenon was caused by glutathione depletion was tested. METHODS AND MATERIALS: The phenomenon of enhanced radiosensitization by nitroheterocyclics after a preincubation period under hypoxic conditions is potentially of importance therapeutically because essentially nonlethal preradiation exposures to the electron affinic drugs cause a much larger radiation sensitization than would otherwise be expected. We have investigated this interesting property of several 2-nitroimidazoles to determine its possible cause and to test various hypotheses about maximizing its possible therapeutic benefit. In view of many observations that thiols are depleted by incubation of cells with nitroimidazoles under hypoxic conditions, we have specifically investigated this aspect of the preincubation effect. Depletion of glutathione was either enhanced by an overnight incubation with buthionine sulfoximine or minimized by preincubation with a 2-nitroimidazole which is sterically inhibited from causing thiol depletion. RESULTS: When conditions were chosen which minimized variations in cellular glutathione content during the preincubation period, no preincubation effect was observed. At low, therapeutically relevant radiation doses, where 2 nitroimidazoles are less efficient sensitizers, the preincubation effect may be even more important, but thiol depletion still minimizes its impact in this region of the dose-response curve. CONCLUSION: These results suggest that the preincubation effect is caused by a "self-sensitization" involving the known enhancement of radiation sensitization by thiol depletion. PMID- 8195032 TI - The role of specific reductases in the intracellular activation and binding of 2 nitroimidazoles. AB - PURPOSE: To determine the relative effectiveness of specific cellular reductases for the activation and binding of 2-nitroimidazoles in vivo. METHODS AND MATERIALS: Monkey kidney cells were transfected with recombinant plasmids to effect intracellular overexpression of P450 reductase and DT-diaphorase. The covalent binding of 2-nitroimidazoles to cellular macromolecules was measured as a function of time of cell incubation at various oxygen concentrations. The effect of allopurinol on cellular binding of radiolabeled 2-nitroimidazoles was also measured. RESULTS: A 1,000-fold overexpression of DT-diaphorase resulted in a small but significant increase in 2-nitroimidazole binding rate. An 80-fold overexpression of cytochrome P450 reductase resulted in a 5-7-fold increase in the binding rate of 2-nitroimidazole. The inhibition of xanthine oxidase by allopurinol had no effect on 2-nitroimidazole binding rates. The amplification of P450 reductase activity within cells was always much larger than the resultant increase in 2-nitroimidazole binding rate, suggesting an enzyme kinetic process less than first order and possibly of 1/2-order. CONCLUSION: These data suggest that cytochrome P450 reductase is the most important enzyme in these cells for reducing 2-nitroimidazoles to intermediates which can covalently bind to cellular macromolecules. Furthermore, since this cellular process demonstrates approximately 1/2-order kinetics, a tissue's capacity for binding 2 nitroimidazole drug in hypoxia should be proportional to the square root of its intracellular P450 reductase level. PMID- 8195033 TI - Bioreductive metabolism of SR-4233 (WIN 59075) by whole cell suspensions under aerobic and hypoxic conditions: role of the pentose cycle and implications for the mechanism of cytotoxicity observed in air. AB - PURPOSE: Measurement of pentose cycle (PC) activity is shown to be a noninvasive means for monitoring the reduction of SR-4233 in whole cells. Comparing these measurements to the actual measurements of drug loss under aerobic and hypoxic conditions helps to define the mechanism for the associated aerobic toxicity. METHODS AND MATERIALS: SR-4233 is activated to a toxic species by bioreductive metabolism. NADPH is required for the activation of the drug by purified enzymes, cell homogenates and whole cells. In vivo the NADPH:NADP+ ratio is maintained by the oxidation of glucose via the oxidative limb of the pentose cycle. By measuring radiolabeled 14CO2 released as a product of this oxidation one can get an accurate measurement of the rate of drug metabolism in whole cells. These results are compared to measurements of drug consumption under aerobic and hypoxic conditions using an HPLC assay. RESULTS: SR-4233 stimulates pentose cycle activity to a greater extent in air then under hypoxia, however, in the presence of added catalase, pentose cycle activity is stimulated to a similar extent under both conditions. The higher levels of PC activity observed in air are due to the production of hydrogen peroxide by the nitroxide free radical undergoing futile redox cycling. The contribution of H2O2 to the observed aerobic cytotoxicity of SR-4233 is minimal however, since toxicity is only slightly reduced in the presence of exogenous catalase and antioxidants such as vitamin E. The level of PC stimulation by SR-4233 suggests that the rate of electron addition to the drug is independent of O2 concentration. The loss of drug from the incubation medium, i.e., conversion to a stable intermediate species, occurs approximately five times faster under nitrogen than in air for A549 cells. It is the rate of drug loss from the cell and not the rate of reduction which best correlates with the observed aerobic and hypoxic toxicity. CONCLUSION: Toxicity in air and in nitrogen is directly related to the rate of drug reduction, i.e., at equivalent levels of drug loss we observe equal levels of cytotoxicity. PMID- 8195034 TI - The effect of low pH and hypoxia on the cytotoxic effects of SR4233 and mitomycin C in vitro. AB - PURPOSE: We examined the effect of acidic pH and hypoxia on the cytotoxicity of SR4233 and mitomycin C in vitro. METHODS AND MATERIALS: The importance of tumor microenvironment to the response of solid tumors to cytotoxic treatment is well established. The bioreductive drug SR4233 has a very substantial selective toxicity for hypoxic cells. We have used both Chinese hamster and human tumor cells to investigate the influence of low pH and hypoxia on the response of cultured cells to treatment with SR4233 or mitomycin C. RESULTS: We found that low pH (6.6) had little effect on the hypoxic toxicity of SR4233; under aerobic conditions, however, low pH substantially increased the cytotoxic effects of 1 h exposure to SR4233, with drug dose enhancement ratios (ER) of 3.9 and 2.5 in V79 and HT-29 cells, respectively. In similar studies with mitomycin C, hypoxia had little effect on the cytotoxicity of mitomycin C in V79 cells, though a low pH of 6.6 enhanced the cytotoxicity under both aerobic and hypoxic conditions (ER approximately 2). In HT-29 cells, neither low pH nor hypoxia had any significant effect on mitomycin C toxicity. CONCLUSION: Low pH, like hypoxia, is a common feature of solid tumors and can be an important determinant of the cytotoxic effect of bioreductive drugs such as SR4233 and mitomycin C. PMID- 8195035 TI - The role of DT-diaphorase in determining the sensitivity of human tumor cells to tirapazamine (SR 4233). AB - PURPOSE: To determine the dependency of the aerobic and hypoxic toxicity of tirapazamine on the intracellular activity of DT-diaphorase. METHODS AND MATERIALS: A panel of 18 human cell lines comprising predominantly small cell and nonsmall cell lung cancer and breast cancer lines were used. The activity of DT diaphorase was determined in cytosolic preparations from cell lysates. The toxicity of tirapazamine was determined using the MTT assay after either 96 or 3 h aerobic exposure or 3 h treatment in hypoxia. RESULTS: The cell lines exhibited a 5000-fold range in DT-diaphorase activity. In toxicity experiments, values of IC50 range from 10.2-120 microM and from 155-1230 for 96 and 3 h aerobic exposures, respectively. In N2, IC50s ranged from 8-55 microM. None of the toxicity values correlate with activity of DT-diaphorase, neither did the ratio of aerobic:hypoxic toxicity (differential toxicity). CONCLUSION: The expression of DT-diaphorase in human tumor cells does not affect the toxicity of tirapazamine. PMID- 8195036 TI - Combining bioreductive drugs (SR 4233 or SN 23862) with the vasoactive agents flavone acetic acid or 5,6-dimethylxanthenone acetic acid. AB - PURPOSE: To determine whether 5,6-dimethylxanthenone acetic acid (DMXAA), a potent analogue of flavone acetic acid (FAA) inhibits blood flow in mouse mammary tumors, and to assess whether DMXAA enhances the antitumor effects of Tirapazamine (SR 4233) and the novel bioreductive drug SN 23862 (a dinitrobenbenzene mustard). METHODS AND MATERIALS: MDAH-MCa-4 mouse mammary tumors were grown i.m. in the leg of C3H/HeN mice. Tumor blood flow was assessed by the pertechnetate clearance method and subsequent growth delay was determined in the same tumors. RESULTS: Administration of DMXAA (65-70 mumol/kg) resulted in inhibition of tumor blood flow to approximately 25% of control values, with no recovery observed up to 36 h post-treatment. Combination of DMXAA with SR 4233 provided a significant increase in tumor growth inhibition relative to either drug alone. In this effect, DMXAA was qualitatively similar to FAA, but was approximately 10 x more potent. The interaction between DMXAA (65 mumol/kg) and SR 4233 (200 mumol/kg) was maximal with SR 4233 given between 15 min before and 60 min after DMXAA. For SN 23862, a similar enhanced growth delay was observed in combination with DMXAA, with no obvious time dependence between 15 min before and 4 h after DMXAA. When mean values for groups treated with SR 4233 (200 mumole/kg) alone and in combination with DMXAA (65-90 mumole/kg) were compared, a correlation was observed between tumor blood flow inhibition and subsequent growth delay. CONCLUSION: DMXAA is a potent inhibitor of blood flow in MDAH-MCa-4 tumors. Combination of this vasoactive drug with bioreductive agents leads to an enhanced antitumor effect. For SR 4233 and DMXAA, this enhanced effect may be predictable by measurement of tumor blood flow inhibition shortly after drug administration. PMID- 8195037 TI - Muscle cramping in phase I clinical trials of tirapazamine (SR 4233) with and without radiation. AB - PURPOSE: Tirapazamine (SR 4233) is a benzotriazine di-N-oxide which acts as a hypoxic cytotoxic agent and as a radiation enhancer when given shortly before or after radiation. Three Phase I clinical trials were designed to determine the maximum tolerated dose, toxicities, pharmacokinetics, and effects on irradiated tumors and normal tissues. METHODS AND MATERIALS: Tirapazamine 9 mg/m2 to 21 mg/m2 was given i.v. 1/2 to 1 h prior to irradiation on a multiple dose schedule of 10 consecutive doses. This was later revised to a three times-per-week schedule for 12 doses. In a second clinical trial, tirapazamine was given in a single dose of 18 mg/m2 to 293 mg/m2 i.v. after irradiation. In a third trial, tirapazamine was administered without irradiation in single doses of 36 mg/m2 to 250 mg/m2, with an option for retreatment. RESULTS: Subjects reported muscle cramping of varying degrees of severity on all three dose schedules. One patient experienced Grade 3 cramping and treatment was discontinued. The most frequent site of cramping were the lower extremities. Creatine phosphokinase (CPK) values were elevated in three patients with associated muscle soreness in one patient. MB (cardiac) isoenzymes were elevated in one patient with no evidence of cardiac muscle damage, and returned to baseline at drug completion. No consistent abnormalities in clinical laboratory values were found. Stretching of the muscle was most effective in relieving the cramping. CONCLUSION: Muscle cramping has been the most frequently reported toxicity in Phase I studies of tirapazamine, though it does not appear to be dose limiting. Dose escalation on the three clinical trials continues. In vitro studies to investigate the cramping are ongoing. PMID- 8195039 TI - The toxic effects, GSH depletion and radiosensitivity by BSO on retinoblastoma. AB - Retinoblastoma is the most common intraocular malignant tumor in children. Previous investigations have reported that buthionine sulfoximine (BSO) can deplete intracellular glutathione (GSH) by specific inhibition and increase cellular radiosensitivity. The toxic effects, GSH depletion and radiosensitivity of BSO on retinoblastoma cells are reported in this paper. GSH content of retinoblastoma cell lines Y-79, So-Rb50 and retinoblastoma xenograft is 2.7 +/- 1.3 x 1.0(-12) mmol/cell, 1.4 +/- 0.2 x 1.0(-12) mmol/cell, and 2.8 +/- 1.2 mumol/g, respectively. The ID50 of BSO on Y-79 and So-Rb50 in air for 3 h exposure is 2.5 mM and 0.2 mM, respectively. GSH depletion by 0.1 mM BSO for 24 h on Y-79 cells and 0.01 mM BSO for 24 h on So-Rb50 cells is 16.35%, and 4.7% of control. GSH depletion in tumor and other organ tissues in retinoblastoma-bearing nude mice after BSO administration is differential. GSH depletion after BSO exposure in Y-79 cells in vitro decreases the Do value of retinoblastoma cells. The SER of 0.01 mM and 0.05 mM BSO for 24 h under the hypoxic condition is 1.21 and 1.36, respectively. Based on these observations, the authors conclude that BSO toxicity on retinoblastoma cells depends on the characteristics of cell line and that BSO can increase hypoxic retinoblastoma cells' radiosensitivity in vitro. Further study of BSO radiosensitization on retinoblastoma in vivo using nude mouse xenograft is needed. PMID- 8195038 TI - Influence of plasma GSH level on acute radiation mucositis of the oral cavity. AB - PURPOSE: To see how pretreatment plasma GSH level influences the severity of acute radiation mucositis of the oral cavity during therapeutic irradiation in patients with oral cancer. METHODS AND MATERIALS: Thirteen patients with squamous cell carcinoma of the oral cavity form the subject material. Radical radiotherapy (60 Gy in 25 fractions over 5 weeks) was given using telecobalt. Pretreatment plasma GSH level was measured by Beutler's method. The normal tissue reaction during radiotherapy was monitored and graded. RESULTS: The GSH levels ranged from 10.6-90.5 microM/L (mean 30.6 microM/L). Those who had higher GSH levels developed less severe mucositis. The mean GSH levels in the groups with different severity of reactions were: Grade 2 (four patients) = 50.7 microM/L; Grade 3 (five patients) = 26.1 microM/L; Grade 4 (two patients) = 20.4 microM/L and Grade 5 (two patients) = 26.1 microM/L; Grade 4 (two patients) = 20.4 microM/L and Grade 5 (two patients) = 13.6 microM/L. CONCLUSION: Plasma GSH estimation has the potential to predict individual sensitivity to acute radiation mucositis and may particularly be useful in hyperfractionated regimes. The study also affirms the radioprotective role of GSH and suggests that this effect is either due to protection against membrane lipid peroxidation (since GSH does not enter the cell freely) or DNA damage (fractionated radiotherapy may permit freer entry of GSH into cell). PMID- 8195040 TI - Regulation of metallothionein mRNA in human hepatoma (HEP3B) cells. AB - PURPOSE: Metallothionein (MT) has been shown to protect cells from the injurious effects of ionizing radiation. MT is an inducible protein and heavy metals can upregulate transcription of the MT gene. The present study was initiated to investigate regulation of MT mRNA synthesis in a human hepatocellular carcinoma (Hep3B) cell line. METHODS AND MATERIALS: MT levels in Hep3B cells were measured by the cadmium-hemoglobin assay. Zinc acetate was used as an inducing agent. Levels of the MT mRNA were determined by the slot blot hybridization technique. Cycloheximide was used as an inhibitor of protein synthesis and actinomycin D was used to block transcription. RESULTS: Zinc acetate (0.1 mM) treatment increased the intracellular levels of MT in Hep3B cells. MT levels peaked at 10 h and remained stable for up to 48 h. A time-dependent increase in the MT mRNA was also observed peaking at 16 h and then declining. Addition of cycloheximide and zinc acetate simultaneously, resulted in a decrease in the levels of MT, whereas MT mRNA levels were increased. There was no significant change in the decay rate of MT mRNA when the cells were treated with actinomycin D (7.5 micrograms/ml) either in the presence or absence of Zn. CONCLUSION: These results suggest that neither the increased synthesis of a metal regulatory factor (MRF) nor an increase in half-life of MT mRNA is involved in the mechanism of increased MT biosynthesis upon addition of Zn. These findings support the hypothesis that a preexisting MRF must complex with Zn to initiate increased transcription for MT. PMID- 8195041 TI - Selective toxicity of buthionine sulfoximine (BSO) to melanoma cells in vitro and in vivo. AB - PURPOSE: Glutathione (GSH) was found to occur in relatively high concentrations in melanoma cells. The purpose of this study was to test the possible cytotoxic effects of an artificial decrease of the elevated GSH level. METHODS AND MATERIALS: The tests were made in vitro and in vivo. In the former case, a total of 11 rodent and human cell lines were studied of which seven were derived from melanomas. After treatment with buthionine sulfoximine (BSO), the decrease of GSH content of the cells and their clonogenic survival was determined. In the in vivo system, single cell suspensions of a subline of the B16 mouse melanoma were injected intravenously into immunocompetent and preirradiated recipients which were subsequently treated with BSO intraperitoneally. Survival time, formation of lung colonies and the weight of metastatic tumor mass in the lungs were the criteria of the BSO effect on the tumor cells. RESULTS: The decrease of the GSH level by BSO was associated with impaired clonogenic survival of the melanoma cells in vitro. Nonmelanoma cells were less affected. BSO treatment of mice inoculated intravenously with melanoma cells resulted in prolonged survival of the animals and impaired metastatic spread of the tumor cells. CONCLUSION: Melanoma cells are particularly sensitive to disturbance of GSH metabolism by treatment with BSO. In view of this selective cytotoxicity of BSO, treatment with this substance may afford a promising therapeutic potential for melanoma. PMID- 8195042 TI - Fungal metabolites. Part 14. Novel potent immunosuppressants, mycestericins, produced by Mycelia sterilia. AB - Mycestericins A, B, C, D and E were isolated from the culture broth of Mycelia sterilia ATCC 20349 along with thermozymocidin (= myriocin). Their structures were elucidated on the basis of spectroscopic studies and chemical evidence. The acetate of mycestericin C was identical with the acetate of 6,7-dihydromyriocin. Mycestericins suppressed the proliferation of lymphocytes in the mouse allogeneic mixed lymphocyte reaction, with a potency similar to that of myriocin. PMID- 8195043 TI - Albaflavenone, a sesquiterpene ketone with a zizaene skeleton produced by a streptomycete with a new rope morphology. AB - A novel antibiotic alpha,beta-unsaturated sesquiterpene ketone, albaflavenone with a zizaene skeleton was isolated from a morphologically novel, highly odorous Streptomyces species which was identified with the species group S. albidoflavus, cluster 1. The new compound, partly responsible for the odour, was assigned the structure of 2R',6,7,7-tetramethyl-1S',8R'- tricyclo-[6.2.1.0(1,5)]undec-5-en-4 one based on spectroscopic studies including 2D NMR (COSY, HETCOR, ROESY, NOE difference) experiments. PMID- 8195044 TI - Biosynthesis of antitumor antibiotic, cytogenin. AB - The biosynthesis of antitumor antibiotic cytogenin, 3-hydroxymethyl-6-methoxy-8 hydroxy-isocoumarin, was studied by feeding 14C- or 13C-labeled compounds to culture of the producing organism, Streptoverticillium eurocidicum MI43-37F11. 14C-Acetate and 14C-methionine were efficiently incorporated into cytogenin as precursors. 13C NMR studies proved that the carbon skeleton of cytogenin is derived from pentaketide intermediate due to head-to-tail condensation of five acetate units and methyl group of 6-OCH3 is derived from methionine. It was suggested that 3-hydroxymethyl and/or 6-methoxy group of cytogenin were metabolized by hydroxylation and/or methylation from three intermediates. PMID- 8195045 TI - Antitumor effect of piericidin B1 N-oxide. AB - Piericidin B1 N-oxide was isolated from a culture broth of Streptomyces sp. as a novel inhibitor of phosphatidylinositol (PI) turnover. Piericidin B1 N-oxide specifically inhibited orthophosphate labeling of PI induced by epidermal growth factor (EGF) without affecting the formation of phosphatidic acid (PA). Like piericidins A1 and B1, piericidin B1 N-oxide inhibited ATP synthesis in A431 cells; however, the effect of piericidin B1 N-oxide on PI synthesis was stronger than that of piericidins A1 and B1. At the concentration inhibiting PI synthesis, piericidin B1 N-oxide showed no inhibitory effect on DNA, RNA, or protein synthesis. We also demonstrated that piericidin B1 N-oxide reversibly inhibited the growth of A431 cells in situ and suppressed the growth of Ehrlich carcinoma in vivo when administered to mice by intraperitoneal (ip) injection. PMID- 8195046 TI - Synthesis and structure-activity relationships of 7 beta-[(Z)-2-(2- aminothiazol 4-yl)-3-(substituted)-2-propenoyl-amino]-3- desacetoxymethylcephalosporins. AB - Synthesis and biological activity of a series of 7 beta-[(Z)-2-(2- aminothiazol-4 yl)-3-(substituted)-2-propenoylamino]-3-cephe m-4-carboxylic acids and their pivaloyloxymethyl esters are described. These acid compounds exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Pivaloyloxymethyl esters of selected compounds in this series were found to be well absorbed from small intestine in mice. PMID- 8195047 TI - Synthesis and structure-activity relationships of 7 beta-[(Z)-2-(2- aminothiazol 4-yl)-3-(substituted)-2-propenoylamino]-3-cephems with C-3 substitutions. AB - Synthesis and biological activity of a series of 7 beta-[(Z)-2-(2- aminothiazol-4 yl)-3-(substituted)-2-propenoylamino]-3-cephe m-4-carboxylic acids with C-3 substitutions and their pivaloyloxymethyl esters are described. These acid compounds exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Pivaloyloxymethyl esters of selected compounds in this series were found to be well absorbed from small intestine in mice. Pivaloyloxymethyl 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-pentenoylamino]-3- carbamoyloxymethyl-3-cephem-4-carboxylase hydrochloride hydrate (S-1108) was finally selected as the candidate for clinical evaluation. PMID- 8195048 TI - Studies on beta-lactam antibiotics. IV. An improved synthesis of 3 (isothiazolylthiomethyl)cephalosporins and its application to new derivatives. AB - An improved synthesis and in vitro activity of cephalosporins with a (4-carboxy-3 hydroxy-5-isothiazolyl)thiomethyl group at the 3-position and its application to the preparation of new derivatives are described. These compounds showed excellent activity against Gram-negative bacteria including beta-lactamase producing strains. Among them, 2f was the most interesting because of its broad spectrum of antibacterial activity, including Gram-positive bacteria, and its outstanding inhibitory potency against Pseudomonas aeruginosa. PMID- 8195050 TI - A rapid and simple screening method for HIV-1 protease inhibitors using recombinant Escherichia coli. PMID- 8195049 TI - New metabolites, tetrahydrofuran lignans, produced by Streptomyces sp. IT-44. PMID- 8195051 TI - New polyenic antibiotics active against gram-positive and gram-negative bacteria. IX. Reclassification of a strain W-315 producing enacyloxins. PMID- 8195052 TI - Inhibitors of diacylglycerol kinase from Drechslera sacchari. PMID- 8195053 TI - Microbial conversion of milbemycins: microbial conversion of milbemycins A4 and A3 by Streptomyces libani. PMID- 8195054 TI - In vitro activity of arbekacin against clinical isolates of methicillin-resistant Staphylococcus aureus in a hospital. PMID- 8195055 TI - Promothiocins A and B novel thiopeptides with a tipA promoter inducing activity produced by Streptomyces sp. SF2741. PMID- 8195056 TI - Is alternative medicine an alternative for the treatment of asthma? PMID- 8195057 TI - What can alternative medicine offer for the treatment of asthma? PMID- 8195058 TI - Bronchial asthma and personality dimensions: a multifaceted association. AB - Personality dimensions seem to play an important role in chronic diseases by maintaining or increasing the patient's physical complaints. This study examines in bronchial asthma: (a) the relationships among clinical data, baseline lung function, and personality traits; and (b) the patient's characteristics related to the physician's judgement about his or her asthma severity. Five questionnaires measuring anxiety, depression, self-consciousness, and subjective symptoms were completed by 51 asthmatic patients. Responses to questionnaires and clinical and demographic data were factor-analyzed. Factor analysis revealed that the physician's severity judgement is based on elderly age, high scores on depression, and longer duration of asthma. PMID- 8195059 TI - The attitude of asthmatic and nonasthmatic adolescents toward gymnastic lessons at school. AB - Questionnaires examining attitudes to physical activity and to gymnastic lessons at school were filled out by 37 asthmatic and 36 healthy adolescents. No significant differences were demonstrated between the two groups. The study suggests that if a positive approach to physical activity is associated with active involvement, attitudinal factors per se should not mitigate against active participation of asthmatic subjects in sports. PMID- 8195060 TI - Longitudinal measurement of airway hyperresponsiveness in selected subjects with persisting pulmonary symptoms. AB - The relationship between airway hyperresponsiveness and pulmonary symptoms was examined longitudinally in 52 subjects. Subjects were part of a larger study, the Natural History of Asthma, and had repeated measures of airway hyperresponsiveness using methacholine. Atopy was determined using skin tests and serum IgE levels. The subjects completed a standardized respiratory questionnaire. Each subject reported respiratory and pulmonary symptoms at either their initial or follow-up visit. The subjects did not, however, have a physician confirmed diagnosis of asthma. Subjects were divided into groups according to the current status of their respiratory symptoms. The four groups included subjects who were initially normal but developed respiratory symptoms at follow-up; subjects who had symptoms at all visits; subjects with respiratory symptoms at their initial visit but who had no symptoms at follow-up; and subjects who had respiratory symptoms prior to their initial visit and who did not have a recurrence during follow-up. There was no statistical difference in airway hyperresponsiveness, IgE, or skin test scores at the initial visits. Subjects who had airway responsiveness were significantly more atopic than subjects who did not have airway responsiveness. Subjects were classified as "consistently positive," "variable," or "consistently negative" responders according to the pattern of methacholine-induced airway hyperresponsiveness. Overall, among the four groups, 33% were consistently positive at all visits, 43% were variable, and 22% were consistently negative. Airway hyperresponsiveness was statistically associated with atopy, but not necessarily associated with questionnaire-based respiratory symptomatology. These factors need to be considered in epidemiological studies of asthma utilizing respiratory questionnaires. PMID- 8195061 TI - Evaluation of conventional press-and-breathe metered-dose inhaler technique in 501 patients. AB - Conventional press-and-breathe metered dose inhalers (MDIs) are widely prescribed but are often difficult for many patients to properly use. A total of 501 patients from different medical specialties were enrolled in this study, which evaluated how the patients used their MDIs. Using a conservative method (minimum number of errors) of determining errors, we found that 388 (77.5%) of the patients made at least one error when demonstrating how they use their MDI for two observers. Using a liberal (maximum number of errors) method of analysis, we found that 447 (89.2%) of the patients made at least one error. There was no difference in errors made stratified by patient gender, patient age, or the medical specialty that treated the patient's pulmonary disease. The two most common errors made by patients were failure to breathe out to functional residual capacity before actuation (225 by minimum method, 280 by maximum method) and not actuating the canister at the start of inhalation (207 by minimum method, 323 by maximum method). Of the patients with improper timing of actuation, the majority (121 patients by minimum method and 187 patients by maximum method) actuated the canister early. In this large patient sample, regardless of which medical specialty provided the treatment, the majority of the patients evaluated had less than optimal MDI technique. Routine assessment of MDI technique should be instituted as standard practice care. PMID- 8195062 TI - Low-dose beta-agonist continuous nebulization therapy for status asthmaticus in children. AB - The role of continuous nebulization therapy (CNT) with low-dose beta (beta) agonist was retrospectively reviewed in 7 children admitted to a pediatric intensive care unit for treatment of acute severe asthma. Clinical asthma score (CAS), alveolar-arterial oxygen difference (A-aDO2), PaCO2, heart rate, and respiratory rate were recorded at 0, 12, and 24 hr of CNT. All patients had a decrease in CAS at 12 hr (p < 0.008) and decreased A-aDO2, PaCO2, respiratory rate, and heart rate at 24 hr (p < 0.008). No patient required escalation of dosage or additional intervention such as intravenous beta-agonist therapy or mechanical ventilation. No patient experienced significant cardiovascular toxicity or hypokalemia. We conclude that CNT with low-dose beta agonists should be considered in the initial approach to therapy in children with acute severe asthma. PMID- 8195063 TI - Quality-of-life factors for parents of children with asthma. PMID- 8195064 TI - The Bacillus subtilis sigma D-dependent operon encoding the flagellar proteins FliD, FliS, and FliT. AB - During a genetic screen to identify metalloregulated loci in Bacillus subtilis, we isolated a Tn917-lacZ insertion in the second gene of an operon downstream of the flagellin (hag) gene. Sequence analysis indicates that this gene encodes a homolog of the enteric flagellar filament cap protein FliD. The fliD gene is followed by homologs of the fliS and fliT genes. Transcription of the fliD-lacZ fusion is sigma D dependent, with peak expression at the end of logarithmic-phase growth. Like other sigma D-dependent genes, expression of fliD-lacZ is greatly reduced by mutations in genes essential for assembly and function of the basal body and hook complex (class II functions). These results suggest that B. subtilis flagellar genes are organized in a hierarchy of gene expression similar to that found in enteric bacteria with hag and fliD as class III genes. Expression from the fliD operon promoter, but not the hag promoter, is repressed by iron, which suggests that the target of metalloregulation is the promoter rather than the sigma D protein. PMID- 8195065 TI - Growth and bioenergetics of alkaliphilic Bacillus firmus OF4 in continuous culture at high pH. AB - The effect of external pH on growth of alkaliphilic Bacillus firmus OF4 was studied in steady-state, pH-controlled cultures at various pH values. Generation times of 54 and 38 min were observed at external pH values of 7.5 and 10.6, respectively. At more alkaline pH values, generation times increased, reaching 690 min at pH 11.4; this was approximately the upper limit of pH for growth with doubling times below 12 h. Decreasing growth rates above pH 11 correlated with an apparent decrease in the ability to tightly regulate cytoplasmic pH and with the appearance of chains of cells. Whereas the cytoplasmic pH was maintained at pH 8.3 or below up to external pH values of 10.8, there was an increase up to pH 8.9 and 9.6 as the growth pH was increased to 11.2 and 11.4, respectively. Both the transmembrane electrical potential and the phosphorylation potential (delta Gp) generally increased over the total pH range, except for a modest fall-off in the delta Gp at pH 11.4. The capacity for pH homeostasis rather than that for oxidative phosphorylation first appeared to become limiting for growth at the high edge of the pH range. No cytoplasmic or membrane-associated organelles were observed at any growth pH, confirming earlier conclusions that structural sequestration of oxidative phosphorylation was not used to resolve the discordance between the total electrochemical proton gradient (delta p) and the delta Gp as the external pH is raised. Were a strictly bulk chemiosmotic coupling mechanism to account for oxidative phosphorylation over the entire range, the deltaGp/deltap ration (which would equal the H+/ATP ratio) would rise from about 3 at pH 7.5 to 13 at pH 11.2, dropping to 7 at pH 11.4 only because of the rise in cytoplasmic pH relative to other parameters. Moreover, the molar growth yields on malate were higher at pH 10.5 than at pH 7.5, indicating greater rather than lesser efficiency in the use of substrate at the more alkaline pH. PMID- 8195066 TI - Genetic analysis of a plasmid-encoded, host genotype-specific enhancement of bacterial fitness. AB - In the absence of antibiotics, carriage of pACYC184 reduces the competitive fitness of an Escherichia coli B genotype that was not previously selected for plasmid carriage, relative to that of an isogenic plasmid-free competitor. However, a host genotype propagated with the plasmid for 500 generations evolved an unexpected competitive advantage from plasmid carriage, relative to its own isogenic plasmid-free segregant. We manipulated the pACYC184 genome in order to identify the plasmid-encoded function that was required for the enhancement of the coevolved host genotype's competitive fitness. Inactivation of the plasmid encoded tetracycline resistance gene, by deletion of either the promoter region or the entire gene, eliminated the beneficial effect of plasmid carriage for the coevolved host. This beneficial effect for the coevolved host was also manifest with pBR322, which contains a tetracycline resistance gene identical to that of pACYC184 but is otherwise heterologous. PMID- 8195067 TI - Organization of the hao gene cluster of Nitrosomonas europaea: genes for two tetraheme c cytochromes. AB - The organization of genes for three proteins involved in ammonia oxidation in Nitrosomonas europaea has been investigated. The amino acid sequence of the N terminal region and four heme-containing peptides produced by proteolysis of the tetraheme cytochrome c554 of N. europaea were determined by Edman degradation. The gene (cycA) encoding this cytochrome is present in three copies per genome (H. McTavish, F. LaQuier, D. Arciero, M. Logan, G. Mundfrom, J.A. Fuchs, and A. B. Hooper, J. Bacteriol. 175:2445-2447, 1993). Three clones, representing at least two copies of cycA, were isolated and sequenced by the dideoxy-chain termination procedure. In both copies, the sequences of 211 amino acids derived from the gene sequence are identical and include all amino acids predicted by the proteolytic peptides. In two copies, the cycA open reading frame (ORF) is followed closely (three bases in one copy) by a second ORF predicted to encode a 28-kDa tetraheme c cytochrome not previously characterized but similar to the nirT gene product of Pseudomonas stutzeri. In one copy of the cycA gene cluster, the second ORF is absent. PMID- 8195068 TI - Characterization of a region of plasmid pBL1 of Brevibacterium lactofermentum involved in replication via the rolling circle model. AB - The minimal region for autonomous replication of pBL1, a 4.5-kb cryptic plasmid of Brevibacterium lactofermentum ATCC 13869 that has been used to construct a variety of corynebacterium vectors, was shown to be contained on a 1.8-kb HindII SphI DNA fragment. This region contains two open reading frames (ORFs) (ORF1 and ORF5) which are essential for pBL1 replication in B. lactofermentum. Accumulation of single-strand intermediates in some of the constructions indicates that plasmid pBL1 replicates via the rolling circle replication model; its plus strand and minus strand were identified by hybridization with two synthetic oligonucleotide probes complementary to each pBL1 strand. ORF1 seems to encode the Rep protein and showed partial homology with sequences for Rep proteins from Streptomyces plasmids which replicate via rolling circle replication such as pIJ101, pSB24, and pJV1. PMID- 8195069 TI - Gonococcal transferrin-binding protein 2 facilitates but is not essential for transferrin utilization. AB - Pathogenic Neisseria species have been shown to scavenge iron from transferrin (Tf), although the mechanism is not yet fully understood. Two iron-repressible proteins that exhibit Tf-binding activity have been identified. This work describes the cloning and sequencing of tbpB, a 2.1-kb gene in N. gonorrhoeae that encodes Tbp2, an 85-kDa iron-repressible lipoprotein. Transcriptional interruption of tbpB had a strong polar effect on tbpA, the structural gene for Tbp1 that is located immediately downstream from tbpB. Such tbpB mutants did not express either Tbp2 or Tbp1, did not bind Tf to whole cells, did not grow on Tf plates, and did not take up iron from Tf. A mutant in which most of tbpB was deleted, presumably leaving tbpA under transcriptional control of the tbpB promoter, was constructed. This mutant did not express Tbp2 but expressed wild type levels of Tbp1 and possessed the phenotype of reduced binding of Tf, decreased iron uptake from Tf, but normal growth on Tf plates. Mutants expressing Tbp2 and not Tbp1 bound less Tf, did not grow on Tf plates, and did not take up iron from Tf. These results suggest that tbpB and tbpA are polycistronic. Tbp2 apparently facilitates binding of Tf but is not essential for acquisition of iron from Tf under these in vitro conditions. PMID- 8195070 TI - Genetic evidence that the XylS regulator of the Pseudomonas TOL meta operon controls the Pm promoter through weak DNA-protein interactions. AB - The activation of the Pm promoter of the meta operon of the TOL plasmid of Pseudomonas putida by its cognate XylS activator protein in the presence and absence of benzoate inducers has been examined in specialized Escherichia coli strains carrying Pm-lacZ fusions and the xylS gene in different configurations in which all controlling elements are present in near native conditions and stoichometry. Expression of a chromosomal Pm-xylX::lacZ fusion was primarily dependent on the addition of an effector at a low xylS gene dosage, but such dependency decreased with increasing levels of the regulator, to the point that hyperproduced XylS could, in the absence of any aromatic effector, raise expression to a level 10(4)-fold higher than normal basal levels. Pm activity never reached a defined saturation level within the range of intracellular concentrations permitted by the intrinsic solubility of the protein, thus suggesting a low degree of occupancy of the OmR and OmL (Om right and left half sites, respectively) operator sequences by XylS. This was confirmed by transcription interference experiments, which indicated that the frequency of occupation of Pm by active XylS is low. This property permits a fine tuning of Pm activity in vivo through changes in intracellular XylS concentrations, as is predicted in current models to account for the coordinated regulation of TOL operons. PMID- 8195071 TI - Halotolerance of Methanobacterium thermoautotrophicum delta H and Marburg. AB - Methanobacterium thermoautotrophicum delta H and Marburg were adapted to grow in medium containing up to 0.65 M NaCl. From 0.01 to 0.5 M NaCl, there was a lag before cell growth which increased with increasing external NaCl. The effect of NaCl on methane production was not significant once the cells began to grow. Intracellular solutes were monitored by nuclear magnetic resonance (NMR) spectroscopy as a function of osmotic stress. In the delta H strain, the major intracellular small organic solutes, cyclic-2,3-diphosphoglycerate and glutamate, increased at most twofold between 0.01 and 0.4 M NaCl and decreased when the external NaCl was 0.5 M. M. thermoautotrophicum Marburg similarly showed a decrease in solute (cyclic-2,3-diphosphoglycerate, 1,3,4,6-tetracarboxyhexane, and L-alpha-glutamate) concentrations for cells grown in medium containing > 0.5 M NaCl. At 0.65 M NaCl, a new organic solute, which was visible in only trace amounts at the lower NaCl concentrations, became the dominant solute. Intracellular potassium in the delta H strain, detected by atomic absorption and 39K NMR, was roughly constant between 0.01 and 0.4 M and then decreased as the external NaCl increased further. The high intracellular K+ was balanced by the negative charges of the organic osmolytes. At the higher external salt concentrations, it is suggested that Na+ and possibly Cl- ions are internalized to provide osmotic balance. A striking difference of strain Marburg from strain delta H was that yeast extract facilitated growth in high-NaCl-containing medium. The yeast extract supplied only trace NMR-detectable solutes (e.g., betaine) but had a large effect on endogenous glutamate levels, which were significantly decreased. Exogenous choline and glycine, instead of yeast extract, also aided growth in NaCl-containing media. Both solutes were internalized with the choline converted to betaine; the contribution to osmotic balance of these species was 20 to 25% of the total small-molecule pool. These results indicate that M. thermoautotrophicum shows little changes in its internal solutes over a wide range of external NaCl. Furthermore, they illustrate the considerable differences in physiology in the delta H and Marburg strains of this organism. PMID- 8195072 TI - Plasmid pSC101 harbors a recombination site, psi, which is able to resolve plasmid multimers and to substitute for the analogous chromosomal Escherichia coli site dif. AB - Plasmid pSC101 harbors a 28-bp sequence which is homologous to dif, the target site of the XerC/XerD-dependent recombination system in Escherichia coli. Using a technique which allows very sensitive detection of plasmid loss, we show that recombination at this site, termed psi for pSC101 stabilized inheritance, causes a moderate increase in pSC101 stability. The role of the psi sequence in site specific recombination has been explored in two other contexts. It was cloned in a derivative of plasmid p15A and inserted into the chromosome in place of dif. In the first situation, psi activity requires accessory sequences and results in multimer resolution; in the second situation, it suppresses the effects of the dif deletion and can promote intermolecular exchanges. Thus, psi is a site whose recombinational activity depends on the context, the first in the cer/dif family known to exhibit such flexibility. PMID- 8195073 TI - Cloning, DNA sequence, and complementation analysis of the Salmonella typhimurium hemN gene encoding a putative oxygen-independent coproporphyrinogen III oxidase. AB - Coproporphyrinogen oxidation is a last step in heme biosynthesis. The biochemically characterized eukaryotic coproporphyrinogen III oxidases have an obligate requirement for molecular oxygen, and a similar enzyme is encoded by the hemF gene in Salmonella typhimurium. Anaerobic heme synthesis requires an oxygen independent coproporphyrinogen oxidase, which is probably encoded by the hemN gene in S. typhimurium. The hemN gene has been cloned from an insertion mutant. The nucleotide sequence was obtained and used for PCR amplification of the wild type gene. A single open reading frame was identified as the hemN gene on the basis of its interruption by the insertion mutation and plasmid complementation studies of hemF hemN double mutants. The predicted HemN protein has 38% amino acid sequence identity to a putative anaerobic Rhodobacter sphaeroides coproporphyrinogen oxidase. The hemN RNA 5' end and the inferred transcription initiation site were mapped by primer extension. The 52.8-kDa HemN protein is expressed from the second ATG codon of the hemN open reading frame. An open reading frame with an unknown function directly upstream of hemN has a striking amino acid sequence, including 11 acidic residues in a row. PMID- 8195074 TI - A role for residue 151 of LamB in bacteriophage lambda adsorption: possible steric effect of amino acid substitutions. AB - LamB is the cell surface receptor for bacteriophage lambda. LamB missense mutations yielding resistance to lambda have been previously grouped in two classes. Class I mutants block growth of lambda with wild-type host range (lambda h+) but support growth of one-step extended-host-range mutants (lambda h). Class II mutants block lambda h but support growth of two-step extended host range mutants (lambda hh*). While Class I mutations occur at 11 different amino acid sites, in five distinct portions of LamB, all the Class II mutations analyzed previously correspond to the same G-to-D change at amino acid 151. We generated by in vitro mutagenesis four different new substitutions at site 151 (to S, V, R, and C). Two of the mutants (G-151-->V [G151V] and G151R) were of Class II, while the two others (G151S and G151C) were of Class I, demonstrating that not only the site but also the nature of the substitutions at residue 151 was critical for the phage sensitivity phenotypes. The introduction of a negatively charged, a positively charged, or an aliphatic nonpolar residue at site 151 of LamB prevented both lambda h+ and lambda h adsorption, indicating that the block is not due to a charge effect. In contrast to G151D, which was sensitive to all the lambda hh* phages, G151V and G151R conferred sensitivity to only four of the five lambda hh* phages. Thus, G151V and G151R represent a new subclass of Class II LamB mutations that is more restrictive with respect to the growth of lambda hh*. Our results agree with the hypothesis that residue 151 belongs to an accessibility gate controlling the access to the phage tight-binding site and that substitutions at this residue affect the access of the phage to the binding site in relation to the size of the substitute side chain (surface area): the most restrictive changes are G151V and G151R, followed to a lesser extent by G151D and they by G151S and G151C. PMID- 8195075 TI - Conjugation-independent, site-specific recombination at the oriT of the IncW plasmid R388 mediated by TrwC. AB - Plasmids containing a direct repeat of plasmid R388 oriT are capable of site specific recombination, which results in deletion of the intervening DNA. This reaction occurs in the presence, but not in the absence, of the region of R388 implicated in DNA processing during conjugation. This region contains three genes, trwA, trwB, and trwC. By using mutants of each of the three genes, it was demonstrated that only trwC is required for the oriT-specific recombination. Further analysis showed that the N-terminal 272 amino acids of the protein are sufficient to catalyze recombination. TrwC is also capable of promoting intermolecular recombination between two plasmids containing oriT, suggesting that double-strand breaks in both plasmid DNAs are involved in the process. Additionally, intramolecular recombination between R388 oriT and R46 oriT did not occur in the presence of both nickases. This suggests that the half-reactions at each oriT are not productive if they occur separately; therefore, an interaction between the recombination complexes formed at each recombining site is required. This is the first report in which a nicking-closing enzyme involved in conjugal DNA transfer promotes oriT-specific recombination of double-stranded DNA in the absence of conjugation. PMID- 8195076 TI - Biochemical properties of a novel metalloprotease from Staphylococcus hyicus subsp. hyicus involved in extracellular lipase processing. AB - Two extracellular proteases from Staphylococcus hyicus subsp. hyicus, ShpI and ShpII, have been characterized. ShpI is a neutral metalloprotease with broad substrate specificity; the gene has been cloned and sequenced. ShpII, characterized here, is mainly produced in the late logarithmic growth phase in contrast to ShpI, which is mainly produced in the late stationary growth phase. ShpII was purified from culture medium of S. hyicus by ammonium sulfate precipitation and DEAE-Sepharose chromatography. The molecular mass, estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was 34 kDa. The temperature optimum of ShpII was 55 degrees C, and the pH optimum was 7.4. ShpII, a neutral metalloprotease, was strongly inhibited by zinc and calcium chelators. The amino-terminal sequence of the active enzyme was similar to the corresponding region of a Staphylococcus epidermidis metalloprotease. The substrate specificity of ShpII was similar to that of thermolysin-like proteases, with the exception that ShpII also recognized aromatic amino acids. We demonstrated in vitro that ShpII, but not ShpI, cleaved the 86-kDa S. hyicus subsp. hyicus prolipase between Thr-245 and Val-246 to generate the mature 46-kDa lipase. Results of additional in vivo experiments supported the model that ShpII is necessary for the extracellular processing and maturation of S. hyicus subsp. hyicus lipase. PMID- 8195077 TI - DNA alkylation repair limits spontaneous base substitution mutations in Escherichia coli. AB - The Escherichia coli Ada and Ogt DNA methyltransferases (MTases) are known to transfer simple alkyl groups from O6-alkylguanine and O4-alkylthymine, directly restoring these alkylated DNA lesions to guanine and thymine. In addition to being exquisitely sensitive to the mutagenic effects of methylating agents, E. coli ada ogt null mutants display a higher spontaneous mutation rate than the wild type. Here, we determined which base substitution mutations are elevated in the MTase-deficient cells by monitoring the reversion of six mutated lacZ alleles that revert via each of the six possible base substitution mutations. During exponential growth, the spontaneous rate of G:C to A:T transitions and G:C to C:G transversions was elevated about fourfold in ada ogt double mutant versus wild type E. coli. Furthermore, compared with the wild type, stationary populations of the MTase-deficient E. coli (under lactose selection) displayed increased G:C to A:T and A:T to G:C transitions (10- and 3-fold, respectively) and increased G:C to C:G, A:T to C:G, and A:T to T:A transversions (10-, 2.5-, and 1.7-fold, respectively). ada and ogt single mutants did not suffer elevated spontaneous mutation rates for any base substitution event, and the cloned ada and ogt genes each restored wild-type spontaneous mutation rates to the ada ogt MTase-deficient strains. We infer that both the Ada MTase and the Ogt MTase can repair the endogenously produced DNA lesions responsible for each of the five base substitution events that are elevated in MTase-deficient cells. Simple methylating and ethylating agents induced G:C to A:T and A:T to G:C transitions in these strains but did not significantly induce G:C to C:G, A:T to C:G, and A:T to T:A transversions. We deduce that S-adenosylmethionine (known to e a weak methylating agent) is not the only metabolite responsible for endogenous DNA alkylation and that at least some of the endogenous metabolites that cause O alkyl DNA damage in E. coli are not simple methylating or ethylating agents. PMID- 8195078 TI - Chromosomal alterations of Candida albicans are associated with the gain and loss of assimilating functions. AB - We have demonstrated that a normal laboratory strain of Candida albicans spontaneously produces mutants which acquire the ability to assimilate certain carbon sources that are not utilized by the parental strain. The examination of mutants acquiring the ability to utilize either sorbose or D-arabinose revealed a few additional phenotypic changes, including the gain and loss of the capacity to assimilate other carbon sources. The change of assimilation patterns resembled the polymorphic variation of assimilation patterns found among different wild type strains of C. albicans. Most importantly, these sorbose- and D-arabinose positive mutants were associated with chromosomal rearrangements, with each class of positive mutants having alterations of specific chromosomes. These findings demonstrated for the first time that chromosomal alterations in C. albicans are involved in genetic variation of fundamental functions of this asexual microorganism. PMID- 8195079 TI - Glu-255 outside the predicted ChvE binding site in VirA is crucial for sugar enhancement of acetosyringone perception by Agrobacterium tumefaciens. AB - Transcriptional activation of the Agrobacterium tumefaciens vir regulon is regulated by phenolics such as acetosyringone (AS), certain monosaccharides, and acidic conditions produced by wounded plant cells. The transmembrane protein VirA acts as an environmental sensor, mediating signal transduction upon perception of these stimuli. Although the periplasmic domain of VirA is not absolutely required for AS-dependent vir gene induction, it is needed for interactions with the periplasmic sugar-binding protein ChvE that result in sugar-induced enhancement of phenolic sensitivity. In this report, we demonstrate that mutations within the periplasmic domain but outside the predicted ChvE binding region can drastically alter the sensitivity of VirA to As. Using site-directed mutagenesis, we have characterized the roles of three individual amino acids in sugar-dependent AS sensitivity and have correlated the induction phenotype with the tumorigenic capacity of strains expressing mutant versions of VirA. Substitution of leucine for Glu-255 abolishes sugar enhancement while replacement with aspartic acid results in a wild-type phenotype. This residue lies outside the predicted ChvE binding site and thus identifies a new region of the VirA periplasmic domain crucial for the enhancement of vir gene induction by carbohydrates. In the absence of inducing sugar, wild-type VirA protein appears to be subject to some form of inhibition that suppresses the maximal level of transcriptional activation; deletions within the periplasmic region relieve this suppression. PMID- 8195080 TI - Phosphoenolpyruvate-dependent maltose:phosphotransferase activity in Fusobacterium mortiferum ATCC 25557: specificity, inducibility, and product analysis. AB - Phosphoenolypyruvate-dependent maltose:phosphotransferase activity was induced in cells of Fusobacterium mortiferum ATCC 25557 during growth on maltose. The disaccharide was rapidly metabolized by washed cells maintained under anaerobic conditions, but fermentation ceased immediately upon exposure of the cell suspension to air. Coincidentally, high levels of a phosphorylated derivative accumulated within the cells. Chemical and enzymatic analyses, in conjunction with data from 1H, 13C, and 31P nuclear magnetic resonance spectroscopy, established the structure of the purified compound as 6-O-phosphoryl-alpha-D glucopyranosyl-(1-4)-D-glucose (maltose 6-phosphate). A method for the preparation of substrate amounts of this commercially unavailable disaccharide phosphate is described. Permeabilized cells of F. mortiferum catalyzed the phosphoenolpyruvate-dependent phosphorylation of maltose under aerobic conditions. However, the hydrolysis of maltose 6-phosphate (to glucose 6 phosphate and glucose) by permeabilized cells or cell-free preparations required either an anaerobic environment or addition of dithiothreitol to aerobic reaction mixtures. The first step in dissimilation of the phosphorylated disaccharide appears to be catalyzed by an oxygen-sensitive maltose 6-phosphate hydrolase. Cells of F. mortiferum, grown previously on maltose, fermented a variety of alpha linked glucosides, including maltose, turanose, palatinose, maltitol, alpha methylglucoside, trehalose, and isomaltose. Conversely, cells grown on the separate alpha-glucosides also metabolized maltose. For this anaerobic pathogen, we suggest that the maltose:phosphotransferase and maltose 6-phosphate hydrolase catalyze the phosphorylative translocation and cleavage not only of maltose but also of structurally analogous alpha-linked glucosides. PMID- 8195081 TI - Transposon Tn5090 of plasmid R751, which carries an integron, is related to Tn7, Mu, and the retroelements. AB - Integrons confer on bacterial plasmids a capability of taking up antibiotic resistance genes by integrase-mediated recombination. We show here that integrons are situated on genetic elements flanked by 25-bp inverted repeats. The element carrying the integron of R751 has three segments conserved with similar elements in Tn21 and Tn5086. Several characteristics suggest that this element is a transposon, which we call Tn5090. Tn5090 was shown to contain an operon with three open reading frames, of which two, tniA and tniB, were predicted by amino acid similarity to code for transposition proteins. The product of tniA (559 amino acids) is a probable transposase with 25% amino acid sequence identity to TnsB from Tn7. Both of these polypeptides contain the D,D(35)E motif characteristic of a protein family made up of the retroviral and retrotransposon IN proteins and some bacterial transposases, such as those of Tn552 and of a range of insertion sequences. Like the transposase genes in Tn552, Mu, and Tn7, the tniA gene was followed by a gene, tniB, for a probable ATP-binding protein. The ends of Tn5090, like those of most other elements producing D,D(35)E proteins, begin by 5'-TG and also contains a complex structure with four 19-bp repeats at the left end and three at the right end. Similarly organized repeats have been observed earlier at the termini of both Tn7 and phage Mu, where they bind their respective transposases and have a role in holoenzyme assembly. Another open reading frame observed in Tn5090, tniC, codes for a recombinase of the invertase/resolvase family, suggesting a replicative transposition mechanism. The data presented here suggest that Tn5090, Tn7, Tn552, and Mu form a subfamily of bacterial transposons which in parallel to many insertion sequences are related to the retroelements. PMID- 8195082 TI - Characterization of the Vibrio cholerae outer membrane heme transport protein HutA: sequence of the gene, regulation of expression, and homology to the family of TonB-dependent proteins. AB - The regulation of hutA, the Vibrio cholerae gene encoding a 77-kDa iron-regulated outer membrane protein required for heme iron utilization, was characterized, and the DNA sequence of the gene was determined. A hutA::Tn5 lac fusion generated previously (D. P. Henderson and S. M. Payne, Mol. Microbiol. 7:461-469, 1993) was transformed into Fur- and Fur+ strains of Escherichia coli and V. cholerae. The results of beta-galactosidase assays on the transformed strains demonstrated that transcription of hutA is regulated by the Fur repressor protein in E. coli and at least partially regulated by Fur in V. cholerae. Analysis of the DNA sequence of hutA indicated that a sequence homologous to the E. coli consensus Fur box was present in the promoter region of hutA. The amino acid sequence of HutA is homologous to those of several TonB-dependent outer member proteins. However, when the V. cholerae heme utilization system, which requires one or more genes encoded by the recombinant plasmid pHUT10 in addition to hutA carried on a second vector, was transferred to a wild-type strain and an isogenic tonB mutant of E. coli, the tonB mutant could utilize heme iron as efficiently as the wild-type strain. These data indicate that the V. cholerae heme utilization system reconstituted in E. coli does not require a functional TonB protein. The tonB mutant transformed with the heme utilization plasmids could not utilize the siderophore ferrichrome as an iron source, indicating that none of the genes encoded on the heme utilization plasmids complements the tonB defect in E. coli. It is possible that a gene(s) encoded by the recombinant heme utilization plasmids encodes a protein serving a TonB-like function in V. cholerae. A region in the carboxy terminus of HutA is homologous to the horse hemoglobin gamma chain, and the amino acids involved in forming the heme pocket in the gamma chain are conserved in HutA. These data suggest that this region of HutA is involved in heme binding. PMID- 8195084 TI - Infection of soybean and pea nodules by Rhizobium spp. purine auxotrophs in the presence of 5-aminoimidazole-4-carboxamide riboside. AB - Purine auxotrophs of various Rhizobium species are symbiotically defective, usually unable to initiate or complete the infection process. Earlier studies demonstrated that, in the Rhizobium etli-bean symbiosis, infection by purine auxotrophs is partially restored by supplementation of the plant medium with 5 amino-imidazole-4-carboxamide (AICA) riboside, the unphosphorylated form of the purine biosynthetic intermediate AICAR. The addition of purine to the root environment does not have this effect. In this study, purine auxotrophs of Rhizobium fredii HH303 and Rhizobium leguminosarum 128C56 (bv. viciae) were examined. Nutritional and genetic characterization indicated that each mutant was blocked in purine biosynthesis prior to the production of AICAR. R. fredii HH303 and R. leguminosarum 128C56 appeared to be deficient in AICA riboside transport and/or conversion into AICAR, and the auxotrophs derived from them grew very poorly with AICA riboside as a purine source. All of the auxotrophs elicited poorly developed, uninfected nodules on their appropriate hosts. On peas, addition of AICA riboside or purine to the root environment led to enhanced nodulation; however, infection threads were observed only in the presence of AICA riboside. On soybeans, only AICA riboside was effective in enhancing nodulation and promoting infection. Although AICA riboside supplementation of the auxotrophs led to infection thread development on both hosts, the numbers of bacteria recovered from the nodules were still 2 or more orders of magnitude lower than in fully developed nodules populated by wild-type bacteria. The ability to AICA riboside to promote infection by purine auxotrophs, despite serving as a very poor purine source for these strains, supports the hypothesis that AICAR plays a role in infection other than merely promoting bacterial growth. PMID- 8195083 TI - Roles of LysP and CadC in mediating the lysine requirement for acid induction of the Escherichia coli cad operon. AB - Expression of the Escherichia coli cadBA operon, encoding functions required for the conversion of lysine to cadaverine and for cadaverine excretion, requires at least two extracellular signals: low pH and a high concentration of lysine. To better understand the nature of the lysine-dependent signal, mutants were isolated which expressed a cadA-lacZ transcription fusion in the absence of lysine while retaining pH regulation. The responsible mutation in one of these isolates (EP310) was in cadC, a gene encoding a function necessary for transcriptional activation of cadBA. This mutation (cadC310) is in a part of the gene encoding the periplasmic domain of CadC and results in an Arg-to-Cys change at position 265, indicating that this part of the protein is involved in responding to the presence of lysine. Three other mutants had mutations mapping in or near lysP (cadR), a gene encoding a lysine transport protein that has previously been shown to regulate cadA expression. One of these mutations is an insertion in the lysP coding region. Thus, in the absence of exogenous lysine, LysP is a negative regulator of cadBA expression. Negative regulation by LysP was further demonstrated by showing that lysP expression from a high-copy-number plasmid rendered cadA-lacZ uninducible. Expression of cadA-lacZ in a strain carrying the cadC310 allele, however, was not affected by the plasmid-expressed lysP. Cadaverine was shown to inhibit expression of the cadA-lacZ fusion in cadC+ cells but not in a cadC310 background. PMID- 8195085 TI - Pullulanase of Thermoanaerobacterium thermosulfurigenes EM1 (Clostridium thermosulfurogenes): molecular analysis of the gene, composite structure of the enzyme, and a common model for its attachment to the cell surface. AB - The complete pullulanase gene (amyB) from Thermoanaerobacterium thermosulfurigenes EM1 was cloned in Escherichia coli, and the nucleotide sequence was determined. The reading frame of amyB consisted of 5,586 bp encoding an exceptionally large enzyme of 205,991 Da. Sequence analysis revealed a composite structure of the pullulanase consisting of catalytic and noncatalytic domains. The N-terminal half of the protein contained a leader peptide of 35 amino acid residues and the catalytic domain, which included the four consensus regions of amylases. Comparison of the consensus regions of several pullulanases suggested that enzymes like pullulanase type II from T. thermosulfurigenes EM1 which hydrolyze alpha-1,4- and alpha-1,6-glycosidic linkages have specific amino acid sequences in the consensus regions. These are different from those of pullulanases type I which only cleave alpha-1,6 linkages. The C-terminal half, which is not necessary for enzymatic function, consisted of at least two different segments. One segment of about 70 kDa contained two copies of a fibronectin type III-like domain and was followed by a linker region rich in glycine, serine, and threonine residues. At the C terminus, we found three repeats of about 50 amino acids which are also present at the N-termini of surface layer (S-layer) proteins of, e.g., Thermus thermophilus and Acetogenium kivui. Since the pullulanase of T. thermosulfurigenes EM1 is known to be cell bound, our results suggest that this segment serves as an S-layer anchor to keep the pullulanase attached to the cell surface. Thus, a general model for the attachment of extracellular enzymes to the cell surface is proposed which assigns the S-layer a new function and might be widespread among bacteria with S-layers. The triplicated S-layer-like segment is present in several enzymes of different bacteria. Upstream of amyB, another open reading frame, coding for a hypothetical protein of 35.6 kDa, was identified. No significant similarity to other sequences available in DNA and protein data bases was found. PMID- 8195086 TI - Transcriptional regulation of the Bacillus subtilis glucitol dehydrogenase gene. AB - The regulatory region of the Bacillus subtilis glucitol dehydrogenase (gutB) gene was divided into three subregions: a promoter, an upstream positive regulatory region, and a downstream negative regulatory region. Data from primer extension, deletion, and site-directed mutagenesis analyses were consistent with two possible models for the gutB promoter. It is either a sigma A-type promoter with an unusually short spacer region (15 bp) or a special sigma A promoter which requires only the hexameric -10 sequence for its function. Sequence carrying just the promoter region (from -48 to +6) failed to direct transcription in vivo. An upstream regulatory sequence was essential for glucitol induction. When this sequence was inserted in a high-copy-number plasmid, an effect characteristic of titration of a transcriptional activator was seen. Downstream from the promoter, there is an imperfect, AT-rich inverted repeat sequence. Deletion of this element did not lead to constitutive expression of gutB. However, the induced gutB expression level was enhanced three- to fourfold. PMID- 8195087 TI - Glucitol induction in Bacillus subtilis is mediated by a regulatory factor, GutR. AB - Expression of the glucitol dehydrogenase gene (gutB) is suggested to be regulated both positively and negatively in Bacillus subtilis. A mutation in the gutR locus results in the constitutive expression of gutB. The exact nature of this mutation and the function of gutR are still unknown. Cloning and characterization of gutR indicated that this gene is located immediately upstream of gutB and is transcribed in the opposite direction relative to gutB. GutR is suggested to be a 95-kDa protein with a putative helix-turn-helix motif and a nucleotide binding domain at the N-terminal region. At the C-terminal region, a short sequence of GutR shows homology with two proteins, Cyc8 (glucose repression mediator protein) and GsiA (glucose starvation-inducible protein), known to be directly or indirectly involved in catabolite repression. Part of the C-terminal conserved sequence from these proteins shows all the features observed in the tetratricopeptide motif found in many eucaryotic proteins. To study the functional role of gutR, chromosomal gutR was insertionally inactivated. A total loss of glucitol inducibility was observed. Reintroduction of a functional gutR to the GutR-deficient strain through integration at the amyE locus restores the inducibility. Therefore, GutR serves as a regulatory factor to modulate glucitol induction. The nature of the gutR1 mutation was also determined. A single amino acid change (serine-289 to arginine-289) near the putative nucleotide binding motif B in GutR is responsible for the observed phenotype. Possible models for the action of GutR are discussed. PMID- 8195088 TI - Evidence that coupling sequences play a frequency-determining role in conjugative transposition of Tn916 in Enterococcus faecalis. AB - The conjugative transposon Tn916 (encodes resistance to tetracycline), originally identified in Enterococcus faecalis, moves by an excision-insertion process in which the rate-limiting step is believed to be excision. Individual transposon containing strains exhibit characteristic mating frequencies which range over several orders of magnitude; the basis of this phenomenon is addressed in the present study. We were able to generate independent single-copy insertions in identical target locations and with similar orientations within a plasmid hemolysin determinant (cylA); however, transposition from this site occurred at very different frequencies (10(-8) to 10(-4) per donor) depending on the individual isolate. DNA sequencing analyses showed that the coupling (junction) sequences differed between isolates and thus appeared to be responsible for differences in excision frequencies. Other experiments showed that inducible transcription into either end of the transposon had no significant effect on transfer. PMID- 8195089 TI - Loss of protein kinase-catalyzed phosphorylation of HPr, a phosphocarrier protein of the phosphotransferase system, by mutation of the ptsH gene confers catabolite repression resistance to several catabolic genes of Bacillus subtilis. AB - In gram-positive bacteria, HPr, a phosphocarrier protein of the phosphoenolpyruvate:sugar phosphotransferase system (PTS), is phosphorylated by an ATP-dependent, metabolite-activated protein kinase on seryl residue 46. In a Bacillus subtilis mutant strain in which Ser-46 of HPr was replaced with a nonphosphorylatable alanyl residue (ptsH1 mutation), synthesis of gluconate kinase, glucitol dehydrogenase, mannitol-1-P dehydrogenase and the mannitol specific PTS permease was completely relieved from repression by glucose, fructose, or mannitol, whereas synthesis of inositol dehydrogenase was partially relieved from catabolite repression and synthesis of alpha-glucosidase and glycerol kinase was still subject to catabolite repression. When the S46A mutation in HPr was reverted to give S46 wild-type HPr, expression of gluconate kinase and glucitol dehydrogenase regained full sensitivity to repression by PTS sugars. These results suggest that phosphorylation of HPr at Ser-46 is directly or indirectly involved in catabolite repression. A strain deleted for the ptsGHI genes was transformed with plasmids expressing either the wild-type ptsH gene or various S46 mutant ptsH genes (S46A or S46D). Expression of the gene encoding S46D HPr, having a structure similar to that of P-ser-HPr according to nuclear magnetic resonance data, caused significant reduction of gluconate kinase activity, whereas expression of the genes encoding wild-type or S46A HPr had no effect on this enzyme activity. When the promoterless lacZ gene was put under the control of the gnt promoter and was subsequently incorporated into the amyE gene on the B. subtilis chromosome, expression of beta-galactosidase was inducible by gluconate and repressed by glucose. However, we observed no repression of beta galactosidase activity in a strain carrying the ptsH1 mutation. Additionally, we investigated a ccpA mutant strain and observed that all of the enzymes which we found to be relieved from carbon catabolite repression in the ptsH1 mutant strain were also insensitive to catabolite repression in the ccpA mutant. Enzymes that were repressed in the ptsH1 mutant were also repressed in the ccpA mutant. PMID- 8195090 TI - Correlation between polyploidy and auxotrophic segregation in the imperfect yeast Candida albicans. AB - In order to clarify the relationship between polyploidization and the capability of phenotypic switching in the imperfect yeast Candida albicans, two types of variants were isolated as segregants from a fusant, which produced a proportion of the cell population with a higher ploidy than the rest, either in a temperature-dependent or -independent manner, when incubated at low (28 degrees C) and high (37 degrees C) temperatures. In the case of the temperature-dependent type of variants, high-ploidy cells appeared at 37 degrees C but rarely at 28 degrees C. This phenotype was named Pldts (temperature-sensitive polyploidization), and the temperature-independent phenotype was called Pld-. The appearance of high-ploidy cells in the culture of the Pldts strain at 37 degrees C was accompanied by a significant increase in the frequency of auxotrophic variants; these variants probably occur as a result of segregation of auxotrophic markers from the heterozygous to the homozygous state. Both Pldts and Pld- phenotypes were recessive in a fusion with a Pld+ parent. An adenine auxotrophic marker (ade1) was introduced into a Pldts strain in a heterozygous state, and the individual high-ploidy cells of this strain, grown at 37 degrees C, were micromanipulated to form colonies, which consisted of red and white sectors appearing at high frequency on a pink background. When the ade1 auxotrophy was introduced into Pld- strains, frequently sectored colonies were produced. These results suggested an increased level of chromosome missegregation in both types of Pld mutants. Analyses by pulsed-field gel electrophoresis of Ade-segregants, derived from a micromanipulated high-ploidy cell of a Pld(ts) strain, suggested the occurrence of nonreciprocal recombination, some of which includes chromosome loss. PMID- 8195091 TI - Isolation and characterization of a generalized transducing phage for Xanthomonas campestris pv. campestris. AB - We have isolated and characterized a lytic double-stranded DNA Xanthomonas campestris pv. campestris bacteriophage (XTP1) capable of mediating generalized transduction. The phage transduces chromosomal markers at frequencies of 10(-5) to 10(-6) transductants per PFU. We demonstrated its genetic utility by the isolation and cotransduction of linked transposon insertions to a nonselectable locus, xgl, required for the cleavage of 5-bromo-3-chloro-indoyl-beta-D galactoside and showed that rif and str alleles in X. campestris are 75% linked. One-step growth experiments showed that the latent and rise periods were each 2 h and the average burst size was 35. The DNA genome is approximately 180 kb, presumably modified in a sequence-specific manner, and may be covalently attached to protein(s). Electron micrographs show the phage particle to have an icosahedral head and contractile tail with tail fibers uniquely attached to a location 40 nm proximal from the end of the tail. PMID- 8195092 TI - Stress induction of clpC in Bacillus subtilis and its involvement in stress tolerance. AB - A member of the clpC subfamily of stress response-related Clp ATPases was cloned from Bacillus subtilis. The B. subtilis clpC gene was induced in response to various stresses, including heat shock. Its product was identified as a general stress protein (Gsp12) described previously. A dramatic increase in the amount of clpC mRNA immediately after exposure to multiple stresses suggested regulation on a transcriptional level. Induction by heat shock was independent of the alternative sigma factor SigB, indicating a new mechanism of heat shock induction in B. subtilis. A clpC insertional mutant had an impaired tolerance for heat shock and salt stress. Furthermore, the mutation triggered the formation of elongated cells, a phenomenon particularly pronounced during stress. PMID- 8195093 TI - Pseudomonas aeruginosa 142 uses a three-component ortho-halobenzoate 1,2 dioxygenase for metabolism of 2,4-dichloro- and 2-chlorobenzoate. AB - Cell extracts of Pseudomonas aeruginosa 142, which was previously isolated from a polychlorinated biphenyl-degrading consortium, were shown to degrade 2,4 dichlorobenzoate, 2-chlorobenzoate, and a variety of other substituted ortho halobenzoates by a reaction that requires oxygen, NADH, Fe(II), and flavin adenine dinucleotide. By using extracts that were chromatographically depleted of chlorocatechol and catechol 1,2-dioxygenase activities, products of the initial reaction with 2,4- or 2,5-dichlorobenzoate and 2-chlorobenzoate were identified by mass spectrometry as 4-chlorocatechol and catechol. In contrast to the well characterized benzoate dioxygenases or the recently described 2-halobenzoate 1,2 dioxygenase from P. cepacia 2CBS (S. Fetzner, R. Muller, and F. Lingens, J. Bacteriol. 174:279-290, 1992) that possess two protein components, the P. aeruginosa enzyme was resolved by ion-exchange chromatography into three components, each of which is required for activity. To verify the distinct nature of this enzyme, we purified, characterized, and identified one component as a ferredoxin (M(r), approximately 13,000) containing a single [2Fe-2S] Rieske-type cluster (electron paramagnetic resonance spectroscopic values of gx = 1.82, gy = 1.905, and gz = 2.02 in the reduced state) that is related in sequence to ferredoxins found in the naphthalene and biphenyl three-component dioxygenase systems. By analogy to these enzymes, we propose that the P. aeruginosa ferredoxin serves as an electron carrier between an NADH-dependent ferredoxin reductase and the terminal component of the ortho-halobenzoate 1,2-dioxygenase. The broad specificity and high regiospecificity of the enzyme make it a promising candidate for use in the degradation of mixtures of chlorobenzoates. PMID- 8195094 TI - Gene cluster controlling conversion to alginate-overproducing phenotype in Pseudomonas aeruginosa: functional analysis in a heterologous host and role in the instability of mucoidy. AB - Conversion to mucoidy, caused by the overproduction of the exopolysaccharide alginate in laboratory and cystic fibrosis strains of Pseudomonas aeruginosa, can occur via frameshift or nonsense mutations in the second gene of the algU mucA mucB cluster. The first gene of the cluster, algU, encodes a putative alternative sigma factor required for algD transcription. The algD gene encodes a critical alginate biosynthetic enzyme and is invariably activated in mucoid P. aeruginosa cells. To investigate the function of the genes controlling conversion to mucoidy, the wild-type algU mucA mucB cluster from the standard genetic strain PAO1 was used to reconstitute algD transcription in Escherichia coli. Transcription of an algD-lacZ chromosomal fusion in E. coli was detected upon introduction of plasmid-borne algU mucA mucB. Moreover, insertional inactivation of either mucA or mucB resulted in further stimulation of transcriptional activity from the algD promoter. This activation was dependent on algU, since a double algU mucA mutation abrogated transcription of algD. These experiments suggest that the phenotypic manifestations of muc mutations, i.e., increased algD expression and mucoid phenotype, depend on the presence of an active algU gene and that this regulator and the factors encoded by the downstream genes interact. Further support for these conclusions came from the investigations of the mechanism of reversion to nonmucoidy in P. aeruginosa, a phenomenon frequently referred to as the instability of mucoid phenotype. Spontaneous nonmucoid derivatives of the mucoid strain PAO578 carrying the mucA22 mutation were examined for the presence of alterations within the algU mucA mucB locus. Point mutations which inactivated algU were detected in some, but not all, nonmucoid revertants. No reversion of the original mucA22 mutation (a deletion of one C) was observed in any of the investigated strains. This observation suggests that the process of conversion to nonmucoidy ban be explained, at least partially, by second-site suppressor mutations and that a fraction of such mutations occurs in algU. PMID- 8195095 TI - The DNA damage-inducible dinD gene of Escherichia coli is equivalent to orfY upstream of pyrE. AB - The DNA damage-inducible gene dinD, originally identified by Kenyon and Walker (C. J. Kenyon and G. C. Walker, Proc. Natl. Acad. Sci. USA 77:2819-2823, 1980) by selection of the dinD::MudI (Ap lac) fusion, is shown here to be equivalent to the open reading frame orfY near pyrE. The evidence for identity between the two genes includes results from P1 transduction, Southern hybridization, and cloning and sequencing of the dinD fusion. No data were obtained that reveal any hints about the function of the dinD gene. PMID- 8195096 TI - Length of the coupling sequence of Tn916. AB - The coupling sequences of conjugative transposons are short variable sequences derived from the DNA flanking the transposon insertion site. We show here that for Tn916 the left coupling sequence is 6 bases long. The right-hand end of the transposon can excise with either four or five T's, but integration occurs to restore the five T's at the transposon's right end. PMID- 8195097 TI - Primary structures of the wild-type and mutant alleles encoding the phosphatidylglycerophosphate synthase of Escherichia coli. AB - The nucleotide sequence of the Escherichia coli pgsA gene, encoding phosphatidylglycerophosphate synthase, is revised to code for an enzyme of 182 amino acid residues, instead of the 216 of a previous work (A. S. Gopalakrishnan, Y.-C. Chen, M. Temkin, and W. Dowhan, J. Biol. Chem. 261:1329-1338, 1986). The revised structure now explains the properties of the enzyme. Three pgsA mutants of different phenotypes were also analyzed: pgsA3, pgsA36, and pgsA10 have single base replacements in codons 60 (Thr-->Pro), 1 (ATG-->ATA), and 92 (Thr-->Ile), respectively. PMID- 8195098 TI - Characterization of IS905, a new multicopy insertion sequence identified in lactococci. AB - IS905 is a multicopy insertion sequence identified in Lactococcus lactis. It is 1313 bp long, bounded by 28-bp imperfect inverted repeats, and encodes a putative transposase of 391 amino acids. One end of IS905 contains sequences that are potentially promoter active. It displays sequence homology to the IS256 class of elements. PMID- 8195099 TI - Thirty-three amino acids of the mature moiety of an unprocessed maltose-binding protein are sufficient for export in Escherichia coli. AB - Maltose-binding protein (MBP) is translocated across the cytoplasmic membrane of Escherichia coli; successful export depends on information in both the signal peptide and the mature moiety of the protein. To determine the shortest portion of the mature region that would maintain detectable entry of MBP into the export pathway, we took advantage of the properties of an MBP species with proline substituted in the +1 position relative to the cleavage site (MBP27-P). This protein efficiently crosses the cytoplasmic membrane but is not processed and acts as a competitive inhibitor of signal peptidase I (leader peptidase). Export of MBP27-P is measured by the inhibition of processing of other proteins, such as ribose-binding protein (RBP). A series of truncated derivatives of MBP27-P were tested for the ability to inhibit processing of RBP. An MBP27-P species with only 33 amino acids of the mature moiety inhibited processing of RBP, indicating that this truncated polypeptide was probably exported and interacted with signal peptidase I. PMID- 8195100 TI - The Escherichia coli efg gene and the Rhodobacter capsulatus adgA gene code for NH3-dependent NAD synthetase. AB - The essential gene efg, which complements ammonia-dependent growth (adgA) mutations in Rhodobacter capsulatus and is located at 38.1 min on the Escherichia coli chromosome, was found to code for NH3-dependent NAD synthetase. Crude extracts from a strain which overproduces the efg gene product contained up to 400 times more activity than crude extracts from the control strain, and the purified Efg protein possessed-NH3-dependent NAD synthetase activity. Glutamine dependent NAD synthetase activity was found in crude extracts of E. coli but not in the purified enzyme, suggesting that it may be catalyzed by an additional subunit. An R. capsulatus strain carrying an adgA mutation was found to be deficient in NAD synthetase activity, and activity was restored by complementation with the E. coli gene. In accordance with the nomenclature proposed for Salmonella typhimurium (K. T. Hughes, B. M. Olivera, and J. R. Roth, J. Bacteriol. 170:2113-2120, 1988), the efg and adgA genes should now be designated nadE. PMID- 8195101 TI - Cloning and characterization of the Inc A/C plasmid RA1 replicon. AB - The Inc A/C plasmids, like Inc P and Inc Q plasmids, have a broad host range. However, their maintenance functions remain to be studied. An autoreplicative region of 2.79 kb named RepA/C, able to replicate both in the family Enterobacteriaceae and in Pseudomonas spp., was isolated and sequenced. The stability, copy number, and incompatibility expression of this replicon were determined. RepA/C and a nonautoreplicative fragment of 16 kb of this replicon were used as probes and showed specific hybridizations with the Inc P3-A/C plasmids from Pseudomonas spp. and members of the Enterobacteriaceae. These probes could be used as tools for identification of the plasmids of this epidemiologically important Inc group. PMID- 8195102 TI - A biochemical study of the intermediary carbon metabolism of Shewanella putrefaciens. AB - Cell extracts were used to determine the enzymes involved in the intermediary carbon metabolism of several strains of Shewanella putrefaciens. Enzymes of the Entner-Doudoroff pathway (6-phosphogluconate dehydratase and 2-keto-3-deoxy-6 phosphogluconate aldolase) were detected, but those of the Embden-Meyerhof-Parnas pathway were not. While several tricarboxylic acid cycle enzymes were present under both aerobic and anaerobic conditions, two key enzymes (2-oxoglutarate dehydrogenase and pyruvate dehydrogenase) were greatly diminished under anaerobic conditions. Extracts of cell grown anaerobically on formate as the sole source of carbon and energy were positive for hydroxypyruvate reductase, the key enzyme of the serine pathway in other methylotrophs, while no hexulose synthase activity was seen. PMID- 8195103 TI - Cloning and sequencing of the genes from Salmonella typhimurium encoding a new bacterial ribonucleotide reductase. AB - A plasmid library of Salmonella typhimurium was used to complement a temperature sensitive nrdA mutant of Escherichia coli. Complementation was obtained with two different classes of plasmids, one carrying the E. coli nrdAB-like genes and the second containing an operon encoding a new bacterial ribonucleotide reductase. Plasmids harboring these new reductase genes also enable obligately anaerobic nrdB::Mud1 E. coli mutants to grow in the presence of oxygen. This operon consists of two open reading frames, which have been designated nrdE (2,145 bp) and nrdF (969 bp). The deduced amino acid sequences of the nrdE and nrdF products include the catalytically important residues conserved in ribonucleotide reductase enzymes of class I and show 25 and 28% overall identity with the R1 and R2 protein, respectively, of the aerobic ribonucleoside diphosphate reductase of E. coli. The 3' end of the sequenced 4.9-kb fragment corresponds to the upstream region of the previously published proU operon of both S. typhimurium and E. coli, indicating that the nrdEF genes are at 57 min on the chromosomal maps of these two bacterial species. Analysis of the nrdEF and proU sequences demonstrates that transcription of the nrdEF genes is in the clockwise direction on the S. typhimurium and E. coli maps. PMID- 8195104 TI - Use of xylE fusions to demonstrate that lsi-1, a Neisseria gonorrhoeae lipooligosaccharide biosynthetic gene, and lsi-3 are not transcriptionally linked. AB - The Neisseria gonorrhoeae lipooligosaccharide biosynthetic gene lsi-1 is preceded by a 281-bp non-protein-encoding sequence, lsi-3, that contains two pairs of inverted repeats. Gonococcal chromosomal lsi-xylE gene fusions were generated to measure the effect of the secondary structure on transcriptional attenuation. The data obtained indicate that lsi-3 and lsi-1 are not transcriptionally linked and therefore that lsi-3 is not involved in the regulation of lsi-1. PMID- 8195105 TI - Biodegradation of 4-methyl-5-nitrocatechol by Pseudomonas sp. strain DNT. AB - Pseudomonas sp. strain DNT degrades 2,4-dinitrotoluene (DNT) by a dioxygenase attack at the 4,5 position with concomitant removal of the nitro group to yield 4 methyl-5-nitrocatechol (MNC). Here we describe the mechanism of removal of the nitro group from MNC and subsequent reactions leading to ring fission. Washed suspensions of DNT-grown cells oxidized MNC and 2,4,5-trihydroxytoluene (THT). Extracts prepared from DNT-induced cells catalyzed the disappearance of MNC in the presence of oxygen and NADPH. Partially purified MNC oxygenase oxidized MNC in a reaction requiring 1 mol of NADPH and 1 mol of oxygen per mol of substrate. The enzyme converted MNC to 2-hydroxy-5-methylquinone (HMQ), which was identified by gas chromatography-mass spectrometry. HMQ was also detected transiently in culture fluids of cells grown on DNT. A quinone reductase was partially purified and shown to convert HMQ to THT in a reaction requiring NADH. A partially purified THT oxygenase catalyzed ring fission of THT and accumulation of a compound tentatively identified as 3-hydroxy-5-(1-formylethylidene)-2-furanone. Preliminary results indicate that this compound is an artifact of the isolation procedure and suggest that 2,4-dihydroxy-5-methyl-6-oxo-2,4-hexadienoic acid is the actual ring fission product. PMID- 8195107 TI - Complications of therapeutic plasma exchange: a recent assessment. AB - The use of therapeutic plasma exchange, particularly for management of patients with neurological disorders, has steadily increased in our hospital since 1991, thus highlighting the need for continuing quality assurance of these services. We have reviewed the hemapheresis records of all 381 therapeutic plasma exchange procedures performed on a total of 63 patients from January 1991 through December 1992. Patients were referred for therapeutic plasma exchange for the following indications: acute Guillain-Barre syndrome, 31 patients (49.2%); chronic inflammatory demyelinating polyneuropathy, 15 patients (23.8%); myasthenia gravis, five patients (7.94%); paraproteinemic neuropathy, five patients (7.94%); thrombotic microangiopathies, six patients (9.52%) and Goodpasture syndrome, one patient (1.6%). Overall, 89% of patients were treated for neurological disorders. Complications of plasma exchange were noted during 17% (n = 65) of procedures involving 49% (n = 31) of patients treated. Approximately 91% of complications were classified as mild (55.4%) or moderately severe (35.4%) and did not prevent successful completion of the procedure. These were largely related to use of citrate-containing anticoagulants and additionally may have reflected the autonomic instability of many of the neuropathy patients. All four (6.15%) severe complications and one of two fatalities were related to the use of central venous access catheters. We conclude that therapeutic plasma exchange can be performed safely with acceptable toxicity caused by mild and moderately severe complications. Major complications may be minimized by careful management of central venous catheters when required for access. PMID- 8195106 TI - Analysis of nonmethylated GATC sites in the Escherichia coli chromosome and identification of sites that are differentially methylated in response to environmental stimuli. AB - Seven GATC sites that are nonmethylated in logarithmic growth phase cells using glycerol as a carbon source were isolated from the Escherichia coli chromosome. Three of these GATC sites are located upstream of the operons gut, mtl, and ppiA, whereas DNA sequences adjacent to three other nonmethylated GATC sites are not homologous to previously identified genes. The seventh nonmethylated GATC site is located downstream of uspA. The protection of this site from DNA methylation requires leucine-responsive regulatory protein and is leucine responsive. The carbon source and the growth phase influenced the protection of the GATC site 5' of the ppiA gene. The other five sites were protected under all the environmental conditions examined. PMID- 8195108 TI - Immunomodulation during treatment of polymyositis with plasmapheresis and immunosuppressive drugs. AB - Immunologic studies were carried out in a patient with polymyositis (PM), who showed increasing muscle strength and decreasing serum creatine phosphokinase levels during 20 weeks of treatment with plasmapheresis in conjunction with prednisone and cyclophosphamide. After an initial rise, serum IgG declined with treatment. Natural killer (NK) lymphocytes were reduced by 74%, B cells by 95%, and T cells by 38%. Spontaneous proliferation of peripheral blood mononuclear cells increased dramatically. Within the CD4+ T cell subset there was increasing maturation as shown by a rise in percent mature (CD29+) cells and reciprocal decline of immature (CD45RA+) cells. At the same time CD4+ T cells became increasingly activated as shown by HLA-DR expression. The percentage of CD8+ T cells increased strongly with treatment, and they showed increased activation and expression of the cytotoxic CD29+ and CD11b- phenotypes. CD8+ T cells exhibiting CD45RA or CD11b+ suppressor phenotypes were overall unchanged; however, on follow up a proportion of CD8+ cells expressed the activated suppressor effector (CD11b CD28-) phenotype. In addition to control of PM by the possible deletion of activated autoreactive B and T lymphocyte clones with cyclophosphamide, the activation and maturation of CD4+ T cells during treatment may have downregulated the autoreactive disease process, either through direct antiidiotypic suppression or by induction of the observed increase in cytotoxic and suppressor CD8+ T cells. PMID- 8195109 TI - Role of extracorporeal photopheresis in the treatment of cutaneous T-cell lymphoma, autoimmune disease, and allograft rejection. AB - Photopheresis is a pheresis-based therapy that is currently available at approximately 70 medical centers worldwide. Recent evidence indicates that extracorporeal photopheresis can significantly prolong life, as well as induce a 60-75% response rate among individuals with advanced cutaneous T-cell lymphoma (CTCL). Moreover, a 10-15% cure rate, in response to photopheresis alone, or in combination with interferon alfa, has been obtained at our institution. These complete responses have been characterized by the complete disappearance of morphologically atypical cells from the skin and blood. Southern blot analysis of peripheral blood specimens have also confirmed the indefinite disappearance of the malignant T-cell clone from the blood of patients with complete responses. Current immunological data obtained from in vitro human studies and from animal models suggest that the basis for the responses of CTCL patients are related to activation of treated macrophages resulting in release of cytokines, including substantial levels of TNF alfa, and, perhaps, to the induction of anti-clonotypic immunity directed against pathogenic clones of T-lymphocytes. In addition to the treatment of CTCL, a potential role for photopheresis in the therapy of autoimmune disease has been suggested by recent pilot studies of pemphigus vulgaris, rheumatoid arthritis, and systemic lupus erythematosus. Furthermore, a randomized, single-blinded trial involving 79 patients with early onset, aggressive systemic sclerosis suggested that photopheresis could beneficially effect the course of the cutaneous thickening in this form of the disease. Lastly, two independent pilot studies of cardiac transplantation have indicated that photopheresis can reverse acute cardiac allograft rejection and potentially suppress ongoing chronic rejection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195110 TI - Protein A immunoadsorption treatment in hematology: an overview. AB - Staphylococcal protein A efficiently binds immunoglobulins and circulating immune complexes (CIC) and provides an effective medium to remove immunoglobulins and CICs from plasma while sparing albumin and most coagulation proteins. Although it activates the complement system its clinical use abrogates the need for plasma expanders necessitated by plasma exchange. Despite anecdotal reports of utility in several hematologic syndromes, publications of clinical trials are available only for autoimmune thrombocytopenic purpura (AITP) and refractoriness to platelet transfusions (RFT) associated with alloimmunization. In the former situation Snyder et al. (Blood 79:2237-2245, 1992) reported on 72 patients with AITP all of whom had failed at least two previous therapies including splenectomy in 68%. Forty-six percent achieved improved platelet counts following treatment. The response was durable (8-26 mo) in all but 10%. Spleen-intact patients could not be differentiated from those who had been splenectomized. Both responders and nonresponders showed significant decreases in CIC and platelet-directed immunoglobulin (PDIG), but responders achieved near-normal levels. The beneficial response of these factors, particularly in spleen-intact patients, warrants a prospective study. In our studies at the University of Minnesota twelve patients with thrombocytopenia secondary to bone marrow failure who were refractory to platelet transfusion were treated with protein A immunoadsorption. Ten had demonstrable antiplatelet Abs (Anti-HLA, HPA, ABO). Seven of 12 demonstrated improved platelet counts and post-transfusion corrected count increments after treatment. This was associated with decreased platelet utilization and clinical bleeding. A prospective controlled clinical trial is justified. PMID- 8195111 TI - Collection of peripheral blood stem cells on spectra. AB - The collection of peripheral blood stem cells by apheresis is a procedure used with increasing frequency in bone marrow transplant. The Spectra Apheresis System is an automated machine allowing the procedure to be tailored to every patient for optimal safety and comfort. The ability to constantly view the products allows the operator flexibility to control the results for an optimal result. PMID- 8195112 TI - Tissue-specific expression of Na(+)-Ca2+ exchanger isoforms. AB - The sodium-calcium exchanger (NCE) plays a critical role in diverse processes in many different tissues including heart, nerve, and kidney. Surprisingly, the NCE is encoded by a single gene. We have isolated and sequenced a rat renal NCE clone, denoted F1, that was identical to previous rat NCEs, except for two unique sequences: one in the 5'-untranslated region and the other at a site of alternative splicing in the coding sequence. To explore these regions further, we examined NCE transcripts in several tissues using "rapid amplification of cDNA 5' ends" and polymerase chain reaction amplification. Three species were identified each with a different 5'-end exon spliced to a common NCE core at nucleotide -34 in the 5'-untranslated region. Based on Northern analysis, each of these species had a unique tissue distribution. Whereas the F1 5'-end variant was abundantly expressed only in kidney, a second variant was expressed mostly in heart, and the third variant was expressed ubiquitously elsewhere. Investigation of the region of alternative splicing in the coding sequence also revealed tissue-specific expression of five major species. These findings indicate that the NCE expression is controlled and regulated under the influence of different promoters in a tissue-specific fashion. Therefore, we propose that the structural complexity of the single NCE gene allows it to respond independently to the unique demands of different environments. PMID- 8195113 TI - Dephosphorylation of osteopontin and bone sialoprotein by osteoclastic tartrate resistant acid phosphatase. Modulation of osteoclast adhesion in vitro. AB - The tartrate-resistant acid phosphatase (TRAP) of skeletal osteoclasts was found to partially dephosphorylate the bone matrix phosphoproteins osteopontin (OPN) and bone sialoprotein (BSP). TRAP also partially dephosphorylated metabolically [32P]PO4-labeled OPN as well as BSP, whereas comparable amounts of either alkaline phosphatase or prostatic acid phosphatase, at their respective pH optima, were ineffective, indicating a certain preference of TRAP for these phosphoprotein substrates. It has previously (Flores, M., Norgard, M., Heinegard, D., Reinholt, F. P., and Andersson, G. (1992) Exp. Cell Res. 201, 526-530) been shown that osteoclasts bind to OPN as well as to BSP coated onto glass. We can now show that the partially dephosphorylated proteins no longer support osteoclast binding. These results indicate that the secretion of TRAP from osteoclasts into the resorption area could exert a regulatory influence on the attachment of the cells to the bone surface. This could imply roles in the development of ruffled borders and/or in the regulation of osteoclast motility on the bone surface. PMID- 8195114 TI - Mg(2+)-dependent cleavage of DNA into kilobase pair fragments is responsible for the initial degradation of DNA in apoptosis. AB - Cleavage of DNA into oligonucleosomal fragments, recognizable as a DNA ladder on agarose gel electrophoresis, is usually considered as the biochemical hallmark of apoptosis. Recently, it has been shown that this internucleosomal cleavage is preceded by the formation of large fragments of DNA of > or = 700, 200-250, and 30-50 kilobase pairs (kbp) in length. Using isolated thymocyte nuclei, we now demonstrate that the formation of these large fragments is Mg(2+)- but not Ca(2+) dependent. Further degradation of > or = 460- and 200-250-kbp fragments to 30-50 kbp fragments but not oligonucleosomal cleavage is also Mg(2+)-dependent but is facilitated by Ca2+. In contrast, formation of oligonucleosomal fragments does not occur in the presence of either Ca2+ or Mg2+ alone but requires the presence of both cations. These results support the hypothesis that the formation of these large fragments and the subsequent internucleosomal cleavage are distinct steps in the degradation of DNA in apoptosis in thymocytes. PMID- 8195115 TI - A single heteromeric receptor complex is sufficient to mediate biological effects of transforming growth factor-beta ligands. AB - Transforming growth factor beta (TGF-beta), a multifunctional cytokine that regulates a variety of biological functions, signals through a heteromeric receptor complex of the type I and type II TGF-beta receptors. The type II receptor, a transmembrane serine-threonine kinase, was cloned based on its ability to directly bind TGF-beta. Recently, a number of candidate type I TGF beta receptors have been isolated. Although only one of these transmembrane kinases (R4) has been shown to mediate TGF-beta-dependent gene activation, others bind TGF-beta when overexpressed in COS cells. Consequently, it has been postulated that the diversity of TGF-beta responses is generated through the association of distinct type I receptors with the type II TGF-beta receptor, thus creating receptor complexes of differential signaling capacities. In contrast to this model, we demonstrate that stable expression of only the R4 type I TGF-beta receptor in a mutant cell line lacking endogenous type I TGF-beta receptor was able to complex with the endogenous type II TGF-beta receptor and restore the effects of TGF-beta on inhibition of cell proliferation and activation of specific genes, regardless of which of the three mammalian isoforms of TGF-beta was used as the ligand. Therefore, R4 acts as a fully functional type I TGF-beta receptor, and the differential effects of TGF-beta are likely mediated by a single receptor complex consisting of R4 and the type II receptor. PMID- 8195116 TI - Jasplakinolide, a cytotoxic natural product, induces actin polymerization and competitively inhibits the binding of phalloidin to F-actin. AB - Jasplakinolide, a naturally occurring cyclic peptide from the marine sponge, Jaspis johnstoni, has both fungicidal and antiproliferative activity. We now report that this peptide is a potent inducer of actin polymerization in vitro. The peptide has a much greater effect on Mg(2+)-actin than on Ca(2+)-actin. Competitive binding studies using rhodamine-phalloidin suggest that jasplakinolide binds to F-actin competitively with phalloidin with a dissociation constant of approximately 15 nM. This compares favorably to the previously reported IC50 of 35 nM for the antiproliferative effect of jasplakinolide on PC3 prostate carcinoma cells. The binding curve suggests that nearest neighbor positive cooperativity influences the binding of jasplakinolide (and perhaps also phalloidin) to F-actin. These results imply that jasplakinolide may exert its cytotoxic effect in vivo by inducing actin polymerization and/or stabilizing pre existing actin filaments. PMID- 8195117 TI - An interaction of wheat germ initiation factor 4B with oligoribonucleotides. AB - The binding of oligoribonucleotides to wheat germ protein synthesis initiation factor eIF-4B was measured by direct fluorescence techniques. An analysis of the equilibrium association constants (Keq) indicates that eIF-4B binding is not affected by the m7GTP cap structure or the AUG. eIF-4B is insensitive to hairpin structures within the oligoribonucleotide. The binding site size is approximately 18 bases. The binding of oligoribonucleotide to eIF-4B as a function of pH, temperature, and ionic strength is also described. The pH-dependent binding showed an increase in binding with increasing pH in contrast to the sharp pH optimum observed for cap binding protein eIF-4E (Carberry, S. E., Darzynkiewicz, E., and Goss, D.J. (1991) Biochemistry 30, 1624-1627). Assuming all tryptophan residues contribute to the observed fluorescence, iodide quenching showed that 8(+/- 1) out 9 of eIF-4B's tryptophan residues are on the surface of the eIF-4B protein. A specific anion effect of Cl- on eIF-4B binding to oligoribonucleotide was found when comparing the ionic strength effect of KC2H3O2 and KCl. PMID- 8195118 TI - In vitro asymmetric binding of the pleiotropic regulatory protein, FruR, to the ace operator controlling glyoxylate shunt enzyme synthesis. AB - The fruR gene of Escherichia coli, which encodes the regulatory protein FruR, was cloned in the pT7-5 expression vector so as to overproduce a protein tagged with 6 histidine residues. By using a one-step chromatographic procedure, FruR was purified to near-homogeneity. Analysis of the protein under both denaturing and nondenaturing conditions indicated that it is a tetramer with a molecular mass of about 150 kilodaltons. The positions of interference between FruR and the operator of the acetate operon were examined. The number and nature of the nucleotides essential for FruR binding were determined by several different techniques: base methylation with dimethyl sulfate, base removal by formic acid and hydrazine, uracil interference, and hydroxyl radical footprinting. It was observed that FruR asymmetrically binds to a 16-base pair DNA sequence located 170 base pairs upstream from the transcriptional start point of the ace operon. PMID- 8195119 TI - An environmentally regulated receptor for diamine oxidase modulates human endothelial cell/fibroblast histamine degradative uptake. AB - Human vascular endothelial cells and fibroblasts express a cell-surface degradative pathway for the multifunctional mediator histamine, which employs a receptor for the metabolic enzyme diamine oxidase (DAO) and results in cellular accumulation of the final metabolite methylimidazoleacetic acid. We demonstrate recognition and regulatory properties of DAO receptors as a function of cellular environmental conditions. Fast and slow ligand binding receptor populations bind DAO at 4 degrees C maximally in 1 and 7 h, respectively; upon warming cells to 37 degrees C both populations participate in degradative uptake of histamine accumulated as methylimidazoleacetic acid. Bound DAO is displaced by heparin with 24-fold greater potency than dextran sulfate, implicating structural specificity of heparin-like glycosaminoglycan moieties as a critical factor in initial receptor/enzyme interaction at fast and slow sites. Receptor-bound DAO is retained under mildly acidic conditions characteristic of early to mid endocytic intracellular compartments and thus could recycle to the plasma membrane intact after internalization. DAO initially bound to receptors in whole cells is retained through cell disruption/membrane fractionation procedures, but DAO binds poorly to isolated membrane fractions or presolubilized receptors, suggesting that the geometry of DAO binding components is not readily maintained upon cell disruption unless DAO is already bound. Cells down-regulate their complement of DAO receptors upon prolonged exposure to DAO. In cells plated at high density, half of the bound DAO becomes nondisplaceable by heparin within 15 min at 37 degrees C, a time consistent with receptor internalization, whereas cells plated at low density retain all bound DAO in a heparin-sensitive state. The protein kinase C activator phorbol 12-myristate 13-acetate modulates DAO receptor number by 35% and total histamine degradative uptake by > 2-fold. Thus this pathway is subject to regulation at the levels of DAO receptor numbers, their state of cell surface display, and additional cellular elements of the degradative pathway with which the DAO receptors interface. PMID- 8195120 TI - DNA damaging agents increase the stability of interleukin-1 alpha, interleukin-1 beta, and interleukin-6 transcripts and the production of the relative proteins. AB - In this study, we addressed the question of whether carcinogens affected the expression of interleukin-1 alpha (IL1 alpha), interleukin-1 beta (IL1 beta), and interleukin-6 (IL6) genes and the production of the relative proteins. Primary cultures of human monocytes were exposed to the alkylating agents mitomycin C (Mit C), methylmethane sulfonate (MMS), and ethylmethane sulfonate (EMS) and tested for the production of IL1 alpha, IL1 beta, and IL6 proteins, as well as for the expression of IL1 alpha, IL1 beta, and IL6 transcripts. The production of IL1 beta and IL6 was significantly augmented by all the three chemicals after 24 48 h of treatment. IL1 alpha was also increased by Mit C and MMS. By Northern blotting analysis, the increased expression of IL1 alpha, IL1 beta, and IL6 genes was shown to occur at 30 min of Mit C and MMS treatment and to decline after 8 h. Similarly, EMS up-regulated the expression of IL1 beta and IL6 genes. The mutagen mediated increase in interleukin transcripts did not require de novo protein synthesis, and it was due to the enhanced half-life of IL1 alpha, IL1 beta, and IL6 mRNAs rather than to the increased rate of gene transcription. These results suggest that carcinogens, in addition to causing DNA mutations and rearrangements, may also affect cell growth and differentiation by enhancing the expression of cytokine genes. PMID- 8195121 TI - Mouse cytochrome P-450EF, representative of a new 1B subfamily of cytochrome P 450s. Cloning, sequence determination, and tissue expression. AB - A novel benz[a]anthracene and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inducible cytochrome P-450 (P450EF), which is very active in polycyclic aromatic hydrocarbon metabolism, has been purified from C3H10T1/2 mouse embryo fibroblasts (Pottenger, L. H., Christou, M., and Jefcoate, C. R. (1991) Arch. Biochem. Biophys. 286, 488-497). P450EF was shown to be immunologically unrelated to the major known P-450 families. A 4.9-kilobase (kb) cDNA encoding P450EF has been isolated from a lambda ZAP cDNA expression library generated from mRNA of TCDD induced C3H10T1/2 cells. This cDNA comprises 175-base pair (bp) 5'-noncoding, 1629-bp open reading, and about 3100-bp 3'-noncoding sequence. A SmaI fragment of the 4.9-kb cDNA hybridized to a 5.2-kb mRNA species equally induced by benz[a]anthracene (10 microM) and TCDD (10 nM) in C3H10T1/2 cells, consistent with the involvement of the Ah receptor in this induction process. The deduced amino acid sequence (543 amino acids), the longest of any known cytochrome P-450, exhibits 41 and 38% identity to mouse CYP1A1 and CYP1A2, respectively, and less but substantial similarity (30-33% identity) to many members of the CYP2 family. There are five extended regions of > or = 50% identity to CYP1A1 as follows: (a) 51-118; (b) 199-222; (c) 326-343 (I-helix, O2-binding threonine); (d) 357-430; and (e) 460-487 (heme-binding cysteine). These sequence relationships suggest that P450EF is a member of a new CYP1B subfamily (mouse CYP1B1). Hybridization of mRNA and immunoblot analyses of microsomes both demonstrated beta-naphthoflavone (beta-NF) inducibility of Cyp1b-1 expression in C3H mouse lung, liver, and uterus although at lower levels relative to Cyp1a-1. The mobility of the beta-NF inducible immunoreactive liver protein was significantly higher than that of the CYP1B1 protein detected in mouse lung, uterus, and C3H10T1/2 cells. Compared with the beta-NF-induced uterus, polycyclic aromatic hydrocarbon-induced uterine fibroblasts exhibited 10-20-fold higher levels of CYP1B1, suggesting that stromal fibroblasts are a major source of the protein. PMID- 8195122 TI - Structural basis by which a recessive mutation in the alpha-subunit of the insulin receptor affects insulin binding. AB - Recently, a mutation substituting Leu for Ser323 in the alpha-subunit of the human insulin receptor has been identified in an insulin-resistant patient. The Leu323 mutation leads to a severe impairment in insulin binding without significantly altering the processing or cell surface expression of the receptor. In order to study how alpha beta half-receptors interact to form the insulin binding site, we cotransfected NIH-3T3 cells with two insulin receptor cDNA constructs: a truncated insulin receptor lacking the C-terminal 43 amino acids (delta 43) and the full-length Leu323 mutant receptor. A clonal cell line from cotransfected cells expresses a hybrid receptor consisting of a Leu323 half receptor and a delta 43 half-receptor. We demonstrate that the Leu323-delta 43 hybrid receptor binds insulin with high affinity. Furthermore, by cross-linking 125I-insulin to immobilized hybrid receptors, we show that only the alpha beta delta half of the hybrid receptor binds insulin. Since the isolated half-insulin receptor has low affinity for insulin, this suggests that the addition of even a non-binding alpha-subunit can result in high affinity binding to the holoreceptor (alpha alpha mut beta delta beta). Both beta and beta delta-subunits of the Leu323-delta 43 hybrid receptor are phosphorylated in vivo and in vitro in an insulin-dependent manner, suggesting an intramolecular transphosphorylation mechanism and that the presence of the Leu323 mutant receptor that lacks an intrinsic high affinity binding site does not prevent the associated beta-subunit from functioning either as a tyrosine kinase or as a phosphate acceptor in the hybrid insulin receptor molecule (alpha alpha mut beta delta beta). Furthermore, we show that the hybrid receptor can phosphorylate insulin receptor substrate-1 (IRS-1) in response to insulin and can be coimmunoprecipitated together with IRS 1 by anti-IRS-1 antibody. PMID- 8195123 TI - Gs regulation of endosome fusion suggests a role for signal transduction pathways in endocytosis. AB - Work from several laboratories indicates that guanine nucleotide-binding proteins (GTP-binding proteins) are required for intracellular vesicular transport. In a previous report we presented evidence indicating that one or more heterotrimeric G proteins regulate fusion between endosomes (Colombo, M. I., Mayorga, L. S., Casey, P. J., and Stahl, P. D. (1992) Science 255, 1695-1697). We now report on experiments showing that Gs plays a role in endosome fusion. We have used several reagents known to modulate Gs function including (i) peptides corresponding to the cytoplasmic domains of G protein-coupled receptors and peptides that mimic interaction of receptors with G proteins, (ii) anti-G protein antibodies, and (iii) cholera toxin. Synthetic peptides corresponding to the third cytoplasmic loop of the beta 2-adrenergic receptor which putatively interact with G alpha s inhibited endosomal fusion. The inhibitory effect of these peptides was prevented by a short preincubation of endosomes with guanosine-5'-3-O-(thio)triphosphate or by phosphorylating the peptide with cAMP-dependent protein kinase. The involvement of Gs in endosome recognition and/or the fusion process was assessed by testing an antibody against the COOH terminus of G alpha s. Anti-G alpha s IgG completely abolished fusion between endosomes. Lastly, preincubation of endosomal vesicles with cholera toxin abrogated fusion in the presence of NAD, whereas no effect was observed in the absence of the cofactor. Taken together these findings indicate a role for Gs in either the mechanism or the regulation of fusion among endosomes. These results raise the possibility that signal transduction through cytoplasmic domains of receptors may participate in the regulation of endocytic trafficking. PMID- 8195124 TI - Structure of the human gene encoding the beta-adrenergic receptor kinase. AB - The beta-adrenergic receptor kinase (beta ARK) specifically phosphorylates the agonist-occupied forms of the beta 2-adrenergic receptor and related G protein coupled receptors. beta ARK is one of the best characterized members of a growing family of G protein-coupled receptor kinases. In this article we report the isolation and structural organization of the human beta ARK gene. The gene spans approximately 23 kilobases and is composed of 21 exons interrupted by 20 introns. Exon sizes range from 52 bases (exon 7) to over 1200 bases (exon 21), intron sizes from 68 bases (intron L) to 10.8 kilobases (intron A). The splice sites for donor and acceptor were in agreement with the canonical GT/AG rule. Functional regions of beta ARK are described with respect to their location within the exon intron organization of the gene. Primer extension and RNase protection assays suggest a major transcription start site approximately 246 bases upstream of the start ATG. Sequence analysis of the 5'-flanking/promoter region reveals many features characteristic of mammalian housekeeping genes, i.e. the lack of a TATA box, an absent or nonstandard positioned CAAT box, high GC content, and the presence of Sp1-binding sites. The extraordinarily high GC content of the 5' flanking region (> 80%) helps define this region as a CpG island that may be a principal regulator of beta ARK expression. PMID- 8195125 TI - Mechanism of GM3 ganglioside synthesis. Kinetic study of rat liver CMP-N neuraminate:lactosylceramide alpha 2,3-sialyltransferase employing 19 molecular species of lactosylceramide. AB - The apparent Km and Vmax of CMP-N-acetylneuraminate:lactosylceramide alpha 2,3 sialyltransferase (LacCer-alpha 2,3-ST) for lactosylceramide and CMP-N acetylneuraminic acid were determined using 19 molecular species of lactosylceramide. The Km for lactosylceramide varied 6-fold among these molecular species of lactosylceramide, but there was a poor correlation between the Km for a particular molecular species and the activity of Lac-Cer alpha 2,3-ST for that molecular species. The Km for CMP-N-acetylneuraminic acid also varied depending on the molecular species of lactosylceramide used as substrate, and there was a good correlation between the Km of Lac-Cer alpha 2,3-ST for CMP-N acetylneuraminic acid and the activity of the enzyme. Kinetic studies indicate that the reaction mechanism of LacCer alpha 2,3-ST is a sequential, Ordered Bi Bi system. From considerations of the effects of the structure of the lactosylceramide molecular species on the Vmax and Km for CMP-N-acetylneuraminic acid, it is likely that LacCer alpha 2,3-ST first binds lactosylceramide and then CMP-N-acetylneuraminic acid and that the rate-limiting step in the reaction is the release of the product GM3. PMID- 8195126 TI - The primary structure of halocyanin, an archaeal blue copper protein, predicts a lipid anchor for membrane fixation. AB - Halocyanin, a small blue copper protein, was isolated from the haloalkaliphilic archaeon Natronobacterium pharaonis. The NH2 terminus was not accessible to Edman degradation. About 70% of the amino acid sequence was determined by protein sequence analysis. The sequence information of two peptides was used for cloning and sequencing the halocyanin gene (hcy). The open reading frame codes for 489 base pairs, which account for a protein with 163 amino acids and a molecular mass of 17,223 Da. The discrepancy between this value and the molecular mass of 15,456 +/- 1.5 Da for the copper-free protein determined by electrospray mass spectrometry can be explained by a post-translational processing of the gene product. The NH2-terminal sequence of the open reading frame contains a motif that is characteristic for prokaryotic lipoproteins. Assuming a similar processing for halocyanin, Cys at position 25 of the primary transcript would be modified by a diphytanyl (glycerol)diether. Subsequently, the precursor is cleaved by a signal peptidase II-like protease and then acetylated at its NH2 terminal alpha-amino group. These modifications would yield a protein with a calculated molecular mass of 15,456 Da. A comparison of the primary structure of halocyanin with a number of other blue copper proteins places it into the plastocyanin-related group. PMID- 8195127 TI - Tax proteins of human T-cell leukemia virus type 1 and 2 induce expression of the gene encoding erythroid-potentiating activity (tissue inhibitor of metalloproteinases-1, TIMP-1). AB - A growth factor-like activity for erythroid cells (erythroid-potentiating activity) is produced by the T-cells infected with human T-cell leukemia virus type 2 (HTLV-2) (Gasson, J. C., Golde, D. W., Kaufman, S. E., Westbrook, C. A., Hewick, R. M., Kaufmann, R. J., Wong, G. G., Temple, P. A., Leary, A. C., Brown, E. L., Orr, E. C., and Clark, S. C. (1985) Nature 315, 768-771) and is reportedly identical with tissue inhibitors of matrix metalloproteinases-1 (TIMP-1) (Docherty, A. J. P., Lyons, A., Smith, B. J., Wright, E. M., Stephens, P. E., Harris, T. J. R., Murphy, G., and Reynolds, J. J. (1985) Nature 318, 66-69). We found that adult T-cell leukemia cell lines infected with HTLV-1 also express high levels of a TIMP-1 transcript. A viral transactivator of HTLV-1, Tax1, in a human T-cell line (Jurkat), was sufficient to stimulate transcription of the TIMP 1 gene. Deletion and mutation analysis of the TIMP-1 gene promoter showed that the AP-1 binding site in the 38-base pair sequence conserved between the human and mouse genes was essential for activation by Tax1. The transactivator of HTLV 2 also stimulated the promoter through the same cis-element. The reported growth promoting activity of TIMP-1 against erythroid cells and potentially against HTLV 1-infected T-cells may modulate the clinical course of adult T-cell leukemia. PMID- 8195128 TI - The S12 ribosomal protein of Podospora anserina belongs to the S19 bacterial family and controls the mitochondrial genome integrity through cytoplasmic translation. AB - In the filamentous fungus Podospora anserina, two nuclear genes are involved in the premature death syndrome associated with a site-specific deletion of the mitochondrial DNA: a mutant allele of the AS1 gene, encoding the cytoplasmic ribosomal protein S12, and an uncharacterized gene closely linked to the mating type locus. We describe here the cloning and the sequencing of the wild-type and two mutant alleles of the AS1 gene. The P. anserina S12 protein belongs to the bacterial S19 ribosomal protein family and shows 72% identity with the S15 human ribosomal protein. Transformation experiments have shown that the AS1-4 mutation itself is responsible for the premature death phenotype and that it corresponds to a Gly to Asp change in the highly conserved COOH-terminal part of the protein. Use of antibodies directed against S12 did not permit detection of the mutant ribosomal protein inside the mitochondria. However, cross-reactions were observed with at least one mitochondrial ribosomal protein displaying a higher molecular weight than S12. The mitochondrial protein does not seem to be a by-product of the AS1 gene but is more likely the mitochondrial homologue of S12. These results strongly suggest that the mutant S12 protein acts indirectly to promote the mitochondrial deletion, via the cytoplasmic translation. PMID- 8195129 TI - Interaction of glutamine 165 in the fourth transmembrane segment of the human neurokinin-1 receptor with quinuclidine antagonists. AB - Substance P binds to and activates the neurokinin-1 receptor with high affinity, thereby modulating several neuronal pathways including pain transmission and neurogenic inflammation. Several high affinity non-peptide antagonists have recently been described. To elucidate the molecular interactions specific for binding to the neurokinin-1 receptor, site-directed mutagenesis has been utilized to identify amino acid residues that interact directly with antagonists. Glutamine 165 in the fourth transmembrane segment was shown to be critical for the binding of CP-96,345 but not SR140333. Analysis of quinuclidine analogs suggests that glutamine 165 interacts with the C-3 heteroatom in this class of antagonists, probably through a hydrogen bond. Glutamine 165 also plays a minor role in the binding of peptides and RP67580. In contrast, serine 169 was determined to be critical for the binding of RP67580. These data indicate that residues 165 and 169 in the fourth transmembrane segment, along with residues in the fifth, sixth, and seventh transmembrane segments as demonstrated previously, form the non-peptide antagonist binding site in the neurokinin-1 receptor. Furthermore, the antagonist binding site overlaps with the binding site for peptide agonists in the fourth and seventh transmembrane segments. PMID- 8195130 TI - Identification of the ATP binding site in tyrocidine synthetase 1 by selective modification with fluorescein 5'-isothiocyanate. AB - Identification of the nucleotide binding site in peptide synthetases has been approached by affinity labeling of tyrocidine synthetase 1 with fluorescein 5' isothiocyanate. Binding was accompanied by irreversible inhibition of the ATP dependent phenylalanine activation reaction and was prevented in the presence of MgATP2-. The reaction obeyed pseudo first-order rate kinetics and was accelerated by Mg2+. Complete inhibition corresponded to incorporation of 2.3 mol of fluorescein 5'-isothiocyanate (FITC)/mol of protein. Upon protection by MgATP2-, about 1 mol of FITC is still incorporated; however, this does not affect activity. The modified synthetase was extensively fragmented by tryptic digestion and the labeled fragments isolated by reverse-phase high performance liquid chromatography. Two peptides, DHQVKIR and LDKMPLTPNDKIDR, have been identified by sequencing, and the FITC conjugate of the former peptide has been detected by laser desorption mass spectrometry. The labeled residues, Lys-422 and Lys-505, are located within highly conserved segments of this new class of synthetases. PMID- 8195131 TI - Analysis of the role of the COOH-terminal domain in the activation, proteolytic activity, and tissue inhibitor of metalloproteinase interactions of gelatinase B. AB - Recombinant human progelatinase B and a COOH terminally truncated version, pro delta426-688 gelatinase B have been prepared from a myeloma cell expression system. Both proenzymes could be processed to active forms by stromelysin-1 to give an NH2 terminus of Phe88, or by treatment with 4-aminophenylmercuric acetate resulting in an NH2-terminal Met75. The kinetics of activation using either treatment was not affected by removal of the enzyme COOH-terminal domain. The specific activities of both gelatinase B and delta426-688 gelatinase B, activated using either method, were found to be similar using either a quenched fluorescent peptide or gelatin as the substrate. Fibroblast monolayers were shown to mediate processing of both progelatinases at similar rates in the presence of either plasminogen or prostromelysin-1. Active wild-type gelatinase B was inhibited by tissue inhibitor of metalloproteinase (TIMP) -1 at a much faster rate than TIMP 2. COOH-terminal truncation of either enzyme or inhibitor gave a marked reduction in the rate constant for TIMP-1 inhibition but had no effect on the rate of TIMP 2 binding. It can be concluded that the COOH-terminal domain of progelatinase B is not involved in autolytic or cellular activation and does not affect the catalytic activity of the enzyme. However, COOH-terminal domain interactions between active gelatinase B and TIMP-1 significantly enhance the rate of complex formation. PMID- 8195132 TI - The mRNA (guanine-7-)methyltransferase domain of the vaccinia virus mRNA capping enzyme. Expression in Escherichia coli and structural and kinetic comparison to the intact capping enzyme. AB - The mRNA (guanine-7-)methyltransferase active site of the heterodimeric vaccinia virus mRNA capping enzyme was previously localized to the carboxyl-terminal third of the large subunit, D1R, associated with the small subunit, D12L (Cong, P., and Shuman, S. (1992) J. Biol. Chem. 267, 16424-16429; Higman, M. A., Bourgeois, N., and Niles, E. G. (1992) J. Biol. Chem. 267, 16430-16437). A plasmid was constructed which directs the coexpression of the carboxyl terminus of the D1R subunit from amino acids 498 to 844 and the D12L subunit in Escherichia coli. The mRNA (guanine-7-)methyltransferase catalytic activity in the isolated domain was found to be kinetically equivalent to that present in the intact enzyme. Through mobility shift and ultraviolet photolinkage analyses, both domains were shown to bind RNA in a saturable fashion. RNA binding was localized predominantly to the large subunit, but a low level of linkage of RNA to D12L was also observed. A low, but reproducible, level of mRNA (guanine-7-)methyltransferase activity was detected in the isolated D1R498-844 subunit demonstrating that the active site resides solely within the large subunit of the capping enzyme. This activity is enhanced 30- to 50-fold by the association of the D12L subunit. PMID- 8195133 TI - Location of the S-adenosyl-L-methionine binding region of the vaccinia virus mRNA (guanine-7-)methyltransferase. AB - The mRNA (guanine-7-)methyltransferase activity of the heterodimeric vaccinia virus mRNA capping enzyme was previously mapped to the carboxyl-terminal 396 amino acids of the large subunit, D1R. This activity is enhanced 30- to 50-fold by the association of the the small subunit, D12L (Higman, M. A., Christen, L. A., and Niles, E. G. (1994) J. Biol. Chem. 269, 14974-14981). Irradiation with ultraviolet light specifically photolinks S-[methyl-3H]S-adenosyl-L-methionine to the large subunit of both the intact capping enzyme and a methyltransferase subdomain, which consists of the D12L subunit associated with the carboxyl terminal 346 amino acids of the D1R subunit. The extent of linkage was shown to be dependent on the length of incubation, intensity of ultraviolet light, and the concentration of both active enzyme and substrate. The covalent modification was inhibited by S-adenosyl-L-homocysteine, a known competitive inhibitor of the mRNA (guanine-7-)methyltransferase activity, demonstrating specific photolabeling of the active site. Sequence-specific chemical cleavage of the photolinked methyltransferase domain with mild acid or cyanogen bromide revealed linkage of S adenosyl-L-methionine to two regions of the large subunit. Analysis of the products of cyanogen bromide and hydroxylamine cleavage mapped the photolinked fragments to amino acids 499 to 579 and 806 to 844 of the D1R subunit. Photolinkage of AdoMet to D1R498-844 was shown to be unaffected by the association of the small subunit. PMID- 8195134 TI - The effects of N helix deletion and mutant F29W on the Ca2+ binding and functional properties of chicken skeletal muscle troponin. AB - To assess the structural and functional significance of the N helix (residues 3 13) of avian recombinant troponin C (rTnC), we have constructed NHdel, in which residues 1-11 have been deleted, both in rTnC and in the spectral probe mutant F29W (Pearlstone, J. R., Borgford, T., Chandra, M., Oikawa, K., Kay, C. M., Herzberg, O., Moult, J., Herklotz, A., Reinach, F. C., and Smillie, L. B. (1992) Biochemistry 31, 6545-6553). Comparison of the far- and near-UV CD spectra (+/- Ca2+) of F29W and F29W/NHdel and titration of the Ca(2+)-induced ellipticity and fluorescence changes indicates that the deletion has little effect on the global fold of the molecule but reduces the Ca2+ affinity of the N domain, but not the C domain, by 1.6-1.8-fold. Comparisons of the mutants NHdel, F29W, and F29W/NHdel with rTnC have been made using several functional assays. In reconstituted troponin-tropomyosin actomyosin subfragment 1 and myofibrillar ATPase systems, both F29W and NHdel have significantly reduced Ca(2+)-activated enzymatic activities. These effects are cumulative in the double mutant F29W/NHdel. On the other hand, maximal isometric tension development in Ca(2+)-activated reconstituted skinned fibers is not affected with F29W and NHdel, although the Ca2+ sensitivity of NHdel in this system is markedly reduced. We conclude that both mutations, NHdel and F29W, are functionally deleterious, possibly affecting interactions of the N domain with troponin I and/or T. PMID- 8195135 TI - The nature of the copper ions in the membranes containing the particulate methane monooxygenase from Methylococcus capsulatus (Bath). AB - It is shown that the particulate methane monooxygenase (pMMO) has an obligate requirement for copper. The MMO activity in the particulate fractions obtained from Methylococcus capsulatus (Bath) cells is found to increase with increasing copper content of the membranes. The enzyme activity from membranes obtained from cells grown at low copper levels can be stimulated further by the addition of Cu(II) ions to the assay medium. The membrane-bound copper ions can exist in both Cu(II) and Cu(I) forms. EPR and magnetic susceptibility characterizations of the membranes indicate the presence of an exchange-coupled trinuclear Cu(II) cluster when the bulk of the copper ions is oxidized. However, the functional form of the enzyme is the reduced or partially reduced form. The copper ions in the membrane fractions as isolated often exhibit a high level of reduction. An EPR spectrum with one unpaired electron spin delocalized over three copper nuclei has been observed for the two-electron reduced trinuclear copper cluster. The high correlation between the copper level in the membranes and enzymatic activity as well as the high reactivity of the reduced copper clusters toward dioxygen strongly indicate that the membrane-bound copper ions constitute the active sites of the pMMO. PMID- 8195136 TI - Identification of matrix metalloproteinase 9 in rabbit osteoclasts. AB - Osteoclasts are multinucleate giant cells that play key roles in bone resorption. To identify genes predominantly expressed in osteoclasts, we screened a cDNA library of osteoclasts with cDNA probes of osteoclasts and alveolar macrophages. Clones specifically hybridizing to the osteoclast probe were isolated and sequenced. The nucleotide sequence of one such clone, F17, was found to share significant similarity with the sequences of human and mouse matrix metalloproteinase 9 (MMP-9) cDNA. By isolation and sequencing of the full-length cDNA, F17 was revealed to encode the rabbit counterpart of MMP-9. By Northern blotting, messenger RNA for MMP-9 was found to be highly and predominantly expressed in isolated osteoclasts when compared with its level in alveolar macrophages and other tissues. By gelatin zymography, gelatinase activity was detected in conditioned medium of isolated osteoclasts, suggesting that MMP-9 is secreted by isolated osteoclasts. Expression of MMP-9 was also observed in in vivo osteoclasts in metacarpal bones of newborn rabbits by in situ hybridization. These facts suggest that MMP-9 is one of the major proteases produced by osteoclasts and possibly plays a role in osteoclastic bone resorption. PMID- 8195137 TI - Localization of ferrochelatase activity within mature pea chloroplasts. AB - Precise localization within the chloroplast of the membrane-bound enzymes involved in heme and chlorophyll biosynthetic pathways is of central importance for better understanding the regulation of the carbon flow into these two pathways. In this study we examine the localization of ferrochelatase activity within mature pea chloroplasts. Our results provide evidence that chloroplast ferrochelatase is associated only with thylakoid membranes. The presence of ferrochelatase in chloroplast thylakoids emphasizes the role of this membrane system in chloroplast protoheme biosynthesis. Furthermore, these results raise the possibility that heme and chlorophyll biosynthesis are compartmentalized in two distinct membrane systems within mature chloroplasts. PMID- 8195138 TI - Phosphorylation of an inhibitory subunit of cGMP phosphodiesterase in Rana catesbeiana rod photoreceptors. II. A possible mechanism for the turnoff of cGMP phosphodiesterase without GTP hydrolysis. AB - In amphibian rod photoreceptor membranes, P gamma, an inhibitory subunit of cGMP phosphodiesterase, is phosphorylated by a protein kinase when P gamma is complexed with the guanosine 5'-O-(3-thiotriphosphate)-bound alpha subunit of transducin (GTP gamma S.T alpha). Five different experiments support the conclusion that the phosphorylated P gamma loses its interaction with GTP gamma S.T alpha. These observations include 1) detection of the inhibitory effect of the GTP gamma S.T alpha.P gamma complex on cGMP phosphodiesterase activity after P gamma in the complex is phosphorylated in a system reconstituted from isolated components, 2) no stimulating effect of GTP gamma S.T alpha on the phosphorylated P gamma-inhibited cGMP phosphodiesterase in the reconstituted system, 3) physical release of phosphorylated P gamma from GTP gamma S.T alpha in the reconstituted system, 4) no inhibitory effect of phosphorylated P gamma on both GTP hydrolysis by T alpha and GTP gamma S/GDP exchange on T alpha in the reconstituted system, and 5) no enhanced activity of cGMP phosphodiesterase by GTP gamma S.T alpha in rod outer segment membranes after incubation of the membranes with the kinase preparation in the presence of ATP. Together with our data that P gamma released with GTP.T alpha is not phosphorylated, and that phosphorylated P gamma inhibits more effectively cGMP phosphodiesterase activity than nonphosphorylated P gamma (Tsuboi, S., Matsumoto, H., Jackson, K. W., Tsujimoto, K., Williams, T., and Yamazaki, A. (1994) J. Biol. Chem. 269, 15016-15023), these observations suggest that, after P gamma is released with GTP.T alpha from catalytic subunits of cGMP phosphodiesterase, P gamma complexed with GTP.T alpha is phosphorylated by a kinase. Then, the phosphorylated P gamma is released from GTP.T alpha and binds to active cGMP phosphodiesterase to inhibit the cGMP hydrolysis. It is suggested that in some G-protein-dependent signal transduction systems G-protein-activated effector may be phosphorylated with a specific kinase and that phosphorylation of the effector results in the turnoff of signal transduction without GTP hydrolysis. PMID- 8195139 TI - Phosphorylation of an inhibitory subunit of cGMP phosphodiesterase in Rana catesbeiana rod photoreceptors. I. Characterization of the phosphorylation. AB - Interaction between the inhibitory subunit (P gamma) and catalytic subunits of cGMP phosphodiesterase is essential for the regulation of cGMP phosphodiesterase in vertebrate rod photoreceptors. P gamma phosphorylation in vitro has been studied using a kinase which is extracted from amphibian rod outer segments. Various chromatographies of the kinase preparation using ionic exchange, gel filtration, and heparin-Sepharose columns indicate that a kinase with M(r) 70,000 is responsible for the P gamma phosphorylation. The kinase does not require any of the known activators for protein kinases but is inhibited by cGMP in a concentration-dependent manner. Together with analysis by laser-desorption mass spectrometry, measurement of 32P radioactivity in phosphorylated P gamma indicates that P gamma extracted with GTP-bound transducin alpha subunit is not phosphorylated and that a phosphate is incorporated into more than 80% of the P gamma by the kinase. Phosphoamino acid analysis, sequencing of phosphorylated peptides derived from phosphorylated P gamma, and phosphorylation of synthetic peptides indicate threonine 22 in P gamma is phosphorylated by the kinase. Phosphorylated P gamma has a higher inhibitory activity for active cGMP phosphodiesterase than non-phosphorylated P gamma. These data suggest that threonine 22 in P gamma is phosphorylated by a specific kinase and that the P gamma phosphorylation governs the interaction between P gamma and catalytic subunits of cGMP phosphodiesterase in vertebrate rod photoreceptors. PMID- 8195140 TI - Transcriptional regulation of the MUC1 mucin gene in colon carcinoma cells by a soluble factor. Identification of a regulatory element. AB - We have investigated a mechanism of the regulation of mucin core polypeptide (MUC1) gene expression, which is induced by a soluble stimulatory factor, in KM12C human colon carcinoma cells. Conditioned media from normal human colon tissues elevated the level of expression of MUC1 mRNA. Transcriptional activation of the MUC1 gene was analyzed by transient expression of MUC1-CAT reporter plasmids containing the 5'-flanking sequence of the MUC1 gene fused to the bacterial chloramphenicol acetyltransferase (CAT) gene. A region between base pairs -531 and -520 of the 5'-flanking sequence of the MUC1 gene was sufficient for the induction of CAT activity by normal colon conditioned medium (NCCM). Mutagenesis of 3 base pairs within the region corresponding to sequence -531 to 517 from ACAGGGAGCGGTTAG to ACAGGGAGATTTTAG substantially decreased the induction of CAT activity by NCCM. Nuclear extracts from untreated or NCCM-treated KM12C cells were tested for their interaction with 32P-labeled oligonucleotides corresponding to this sequence. A specifically retarded band was identified after electrophoretic analysis. The quantity or mobility of this band was not changed by NCCM treatment. When an oligonucleotide with three point mutations was used as a competitor, the retarded band remained at the same position. This element (positions -531 to -520), which we call the responsive mucin element, does not contain any sequence that corresponds to previously described cis-acting elements. A protein component complexed with this sequence was identified with a molecular mass of approximately 70 kDa by SDS-polyacrylamide gel electrophoresis. PMID- 8195141 TI - Formation of intersubunit disulfide bonds and properties of the single histidine and cysteine residues in each subunit relative to the decameric structure of cyanase. AB - Reaction of the single cysteine residue in each subunit of cyanase with certain SH reagents gives an active decameric derivative that dissociates reversibly to an inactive dimer derivative (Anderson, P. M., Johnson, W. V., Korte, J. J., Xiong, X., Sung, Y.-c., and Fuchs, J. A. (1988) J. Biol. Chem. 263, 5674-5680). Reaction of mixed disulfide dimer derivatives of cyanase with dithiothreitol at 0 degree C results in formation of a disulfide bond between the subunits in the dimer. The disulfide dimer was inactive and did not associate to a decamer; the intersubunit disulfide bond could not be formed when the dimers were associated as a decamer. The two SH groups apparently are in close proximity to each other in the dissociated dimer but not when the dimer is associated to a decamer. Substitution of glycine for the cysteine residue or of tyrosine, asparagine, glycine, valine, or leucine for the single histidine residue in each subunit gave mutant enzymes that were active. However, H113N, H113Y, and C83G were unstable at low temperature and/or ionic strength, dissociating reversibly to an inactive dimer. Efficient reassociation required the presence of bicarbonate or cyanate analog. The results are consistent with a proposed single site per subunit model explaining apparent half-site binding of substrates and the requirement of decameric structure for activity. PMID- 8195142 TI - Repression of estrogen-dependent stimulation of the oxytocin gene by chicken ovalbumin upstream promoter transcription factor I. AB - The orphan receptor chicken ovalbumin upstream promoter transcription factor I (COUP-TF I) fully prevented not only the activation of the oxytocin gene by retinoic acid and thyroid hormone but also completely repressed the estrogen dependent stimulation in transfected P19 EC cells. DNase I footprinting showed that the COUP-TF I protein bound to the 5'-flanking region of the oxytocin gene at the site of the distal composite hormone response element, which mediates the responses to estrogen, retinoic acid, and thyroid hormone. Electrophoretic mobility shift assay using this composite hormone response element as probe showed that COUP-TF I and the estrogen receptor competed for binding but did not form a heterodimer. The binding by COUP-TF I was stronger than the binding of the estrogen receptor. Thus, the mechanism of repression involves occupancy of integrated binding sites. By mutagenesis of the composite hormone response element, the COUP-TF I binding site and the estrogen response element could be separated, resulting in functional dissociation of the repressive action of COUP TF I and the induction by estrogen. The results show that repression of gene expression by COUP-TF I is not limited to receptors that act through heterodimerization but also extends to the homodimer-forming estrogen receptor in a context-dependent manner. This interaction between COUP-TF I and the estrogen receptor may provide a physiological mechanism of selective antagonism of gene regulation by estrogens. PMID- 8195143 TI - Molecular cloning and sequencing of a 58-kDa membrane- and microfilament associated protein from ascites tumor cell microvilli with sequence similarities to retroviral Gag proteins. AB - The MAT-C1 subline of the 13762 rat mammary adenocarcinoma has highly stable, branched microvilli and immobile cell surface receptors. A membrane- and microfilament-associated 58-kDa protein (p58) in the MAT-C1 microvilli has been implicated in the stabilization of the microvilli and microfilament-membrane interactions. This protein is associated with a high M(r) glycoprotein complex containing the (proto)oncogene p185neu and other signal transduction components in a putative microfilament-associated signal transduction particle. Amino acid sequences were obtained from two trypsin peptides of p58. Screening a MAT-C1 cDNA library with a degenerate oligonucleotide derived from the larger peptide and polymerase chain reaction amplification of cDNA ends permitted the isolation of overlapping cDNAs encoding the 427-amino acid open reading frame of p58. In vitro transcription and translation using a full-length cDNA gave a protein of approximately 55 kDa, which reacts with anti-p58 antiserum and reconstitutes into a complex with actin and glycoproteins from the membrane-microfilament interaction site. When COS-7 cells were transfected with the full-length cDNA, p58 was localized in a punctate distribution. In addition, the transfected cells exhibited fewer microfilament cables than untransfected neighboring cells. The amino acid sequence showed a surprising similarity to mammalian retroviral Gag proteins and included regions corresponding to p15, p12 and the N-terminal 80% of p30. Comparisons of p58 and the corresponding regions of the Gag proteins for Moloney murine leukemia virus indicated that about 60% of their amino acid residues were identical. These studies suggest that p58 is the product of an endogenous retroviral gene whose expression as a cellular protein alters the properties of the tumor cell to provide a selective advantage for tumor growth in the animal. PMID- 8195144 TI - Human acylpeptide hydrolase. Studies on its thiol groups and mechanism of action. AB - The presence of a cysteine residue(s) near the active site of acylpeptide hydrolase was suggested by inactivation of the enzyme with sulfhydryl-modifying agents and by the substantial protection against inactivation afforded by the competitive inhibitor acetylmethionine. 5,5'-dithiobis-(2-nitrobenzoate) titrations of the native and the denatured enzyme together with analysis for cysteic acid after performic acid oxidation showed that the enzyme contained 12 free SH groups and three disulfide bonds/monomer. Chemical modification with radiolabeled iodoacetamide led to the labeling of Cys-30 and Cys-64 suggesting that one or both of these Cys residues are close to the active site. Modification of one or both of them probably inhibits the enzyme either because of a distortion of the active site or because the adducts present a barrier to the efficient diffusion of substrates into and products out of the active site. Studies on the mechanism of action of acylpeptide hydrolase have employed p nitrophenyl-N-propyl carbamate as a potent active site-directed inhibitor. Enzyme inactivation, which follows pseudo first-order kinetics, is diminished by the competitive inhibitor acetylmethionine. The inhibited enzyme slowly regains activity at a rate that is increased in the presence of the nucleophile hydroxylamine. A general mechanism involving an acyl-enzyme intermediate is supported by evidence for the formation of acetyl-alanyl hydroxamate during hydrolysis of acetyl-alanine p-nitroanilide in the presence of hydroxylamine. The effect on Vmax and Km during this reaction indicate that hydrolysis of the acyl enzyme intermediate is rate-limiting. PMID- 8195145 TI - Different functions of Smg GDP dissociation stimulator and mammalian counterpart of yeast Cdc25. AB - We have previously shown that both Smg GDP dissociation stimulator (GDS) and mammalian Cdc25 (mCdc25) stimulate the GDP/GTP exchange reaction of Ki-Ras and that Smg GDS is active only on the post-translationally lipid-modified form of Ki Ras, whereas mCdc25 is active on both the lipid-modified and unmodified forms but is more active on the lipid-modified form. In the present study, we compared more detailed kinetic properties of Smg GDS and mCdc25 by use of the lipid-modified form of Ki-Ras as a common substrate. Both Smg GDS and mCdc25 stimulated the dissociation of GDP from Ki-Ras and formed the stable binary complex with Ki-Ras. In the presence of guanosine 5'-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. mCdc25 stimulated the dissociation of GDP from both the membrane-bound and soluble forms of Ki-Ras, whereas Smg GDS was far less active on the membrane bound form than on the soluble form. Moreover, Smg GDS translocated the GTP gamma S-bound form of membrane-bound Ki-Ras to the soluble fraction as the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras, whereas mCdc25 did not show this activity. These results suggest that Smg GDS and mCdc25 play different roles in the regulation of Ki-Ras. PMID- 8195146 TI - Identification and characterization of SPRK, a novel src-homology 3 domain containing proline-rich kinase with serine/threonine kinase activity. AB - Protein kinase play important roles in the growth and differentiation of cells. We have isolated cDNA clones from the human megakaryocytic cell line CMK11-5 that encode a novel protein kinase, which we call SPRK (src-homology 3 (SH3) domain containing proline-rich kinase). The gene sequence predicts an 847-amino acid protein kinase with a unique domain arrangement. An amino-terminal glycine-rich region is followed by an SH3 domain and a kinase domain that is similar to both tyrosine and serine/threonine kinases. Adjacent to the kinase domain are two closely spaced leucine/isoleucine zipper motifs and a stretch of basic amino acids that resembles karyophilic nuclear localization signals. The COOH-terminal half of SPRK is basic, and proline accounts for 24% of the COOH-terminal 216 amino acids. The sprk gene is widely expressed as a 4-kilobase transcript in adult and fetal human tissues. Transfection of 293 cells with a vector encoding an epitope-tagged SPRK results in the expression of a 95-kDa protein. The epitope tagged SPRK becomes phosphorylated on serine and threonine residues in an in vitro kinase assay, whereas SPRK variants with point mutations in the predicted ATP-binding site fail to become phosphorylated. These data indicate that SPRK has serine/threonine kinase activity. The SH3 domain of SPRK is interrupted by a unique 5-amino acid insert whose location in the SH3 consensus sequence is the same as that of the inserts found in the SH3 domains of neuronal SRC and of the p85 subunit of phosphatidylinositol 3-kinase. PMID- 8195147 TI - Evidence for an internal regulatory region in a human nonmuscle myosin heavy chain gene. AB - We have isolated genomic clones which encode the promoter and flanking region of human nonmuscle myosin heavy chain (MHC)-A. The sequence of this region shows many features typical of a housekeeping gene; there is no TATA element and no functional CAAT box. The GC content is high, having an average GC content of 74% in the 600 base pairs (bp) surrounding the transcriptional start sites, and multiple GC boxes (putative Sp1 binding sites) are present. A number of nucleotide sites are utilized for the initiation of transcription. Promoter activity was monitored using luciferase as a reporter following transient transfection into NIH 3T3 cells. Analysis of 5' and 3' deletion mutants in the promoter region defines the core promoter as extending from nucleotide -112 to +61, where +1 is a major transcriptional start site. An essential sequence for core promoter activity resides in the 36-bp region from -77 to -112 which includes a single potential AP-2 binding site and a single potential Sp1 binding site. The region just downstream from the transcriptional start site (between +62 and +257) was found to be involved in cell type-specific activation of nonmuscle MHC-A gene expression. The increase in luciferase activity due to this proximal downstream region is approximately 15-fold in NIH 3T3 cells, but no increase was observed in C2C12 myotubes and neuroblastoma cells. This 196-bp region, which consists of 100 bp from exon 1 and 96 bp from intron 1, functions in a position- and orientation-dependent manner. Quantitation of luciferase mRNA content driven by the MHC-A promoter, using both competitive polymerase chain reaction and RNase protection assays, revealed that the increase seen in luciferase mRNA due to the 196-bp fragment is approximately 5-fold in NIH 3T3 cells. This only accounts for about one-third of the total increase seen in luciferase activity (protein amounts). Thus, this proximal downstream region appears to activate gene expression in NIH 3T3 cells via both pretranslational (transcription and/or mRNA stability) and translational mechanisms. PMID- 8195148 TI - Human hepatitis virus X gene encodes a regulatory domain that represses transactivation of X protein. AB - The human hepatitis B virus (HBV) X gene seems to be essential for establishment of viral infection, and the X gene product, HBx, transactivates virus and host genes through a wide variety of cis-elements, whereas regulation of HBx has not been fully understood. We found that transactivation-negative HBx mutants truncated at the C-terminal portion specifically repressed the HBx transactivation in trans. The ability to trans-repress the HBx transactivation is confined to the N-terminal third of HBx. Transactivation-positive constructs of HBx were divided into two groups by their sensitivity to trans-repression due to the presence of the N-terminal third. Thus the regulatory domain, the N-terminal third, is separated from the transacting domain and responsible for the negative regulations, the trans-repression and sensitivity to X trans-repression. A possible direct association between the HBx regulatory domains was tested by far Western blotting using purified fused forms of HBx proteins. The regulatory domain was found to associate preferentially with the full HBx or the regulatory domain, but not with the transacting domain. Taken together, it is possible that HBx has a self-regulatory mechanism that avoids excessive HBx transactivation and is important for regulation of X gene expression. PMID- 8195149 TI - Interaction of fluorescently labeled analogues of the amino-terminal fusion peptide of Sendai virus with phospholipid membranes. AB - A peptide representing the NH2-terminal (33 amino acid residues) of the fusion protein (F) of Sendai virus, as well as its Gly12-->Ala12 mutant, were synthesized, fluorescently labeled, and spectroscopically and functionally characterized. Peptide-induced vesicle fusion was demonstrated by a combination of increased visible absorbance, lipid mixing assay, and electron microscopy. Both peptides, with the mutant peptide being significantly more potent, were shown to induce membrane fusion and bilayer perturbation of negatively charged phospholipid vesicles. These results are consistent with a previous study that showed that a similar mutation in the homologous NH2-terminal segment of simian virus 5 greatly enhanced syncytium formation (Horvath, C. M., and Lamb, R. A. (1992) J. Virol. 66, 2443-2455). Circular dichroism spectroscopy revealed similar high alpha-helical contents of both peptides in methanol and in trifluoroethanol. Using fluorescently labeled peptide analogues we found that (i) the peptides' membrane partition coefficients are in the range of 10(5) M-1; (ii) the NH2 terminus of the wild-type peptide is located within the lipid bilayer, whereas that of the variant peptide lies on the surface; and (iii) both peptides tend to self-associate in their membrane-bound state. The results support a model in which an alpha-helical secondary structure and self-aggregation of peptides are necessary conditions for membrane fusion. The observed differences in the peptides' fusogenic abilities are hypothesized to result from differences in the peptides' degree of penetration into the membrane, induction of membrane destabilization, and ability to cause vesicles to aggregate. The data support Sendai virus-cell fusion models in which the fusion peptide plays a crucial role in fusion induction by destabilizing the bilayer and by triggering the association of viral fusion protein molecules. PMID- 8195150 TI - Structural requirements of substrate DNA for binding to and cleavage by RuvC, a Holliday junction resolvase. AB - To elucidate the molecular mechanism of the resolution of Holliday junctions by Escherichia coli RuvC protein, we studied biochemical properties of the protein using various synthetic DNA junctions as model substrates. RuvC cleaves not only a four-way junction but also three-way junctions efficiently. The central core of homology in the junction is essential for the substrates to be cleavable by RuvC. Although the divalent cations are essential for the endonuclease activity, RuvC efficiently forms specific complexes with four-way junctions in the absence of the cations, irrespective of the presence of homologous core sequences. By using T7 endonuclease I as a probe, we studied the topology of the substrate junctions used in our study. The results suggest that RuvC cleaves the three-way junctions with homology core when they become four-way conformers. From the present studies, we propose that RuvC initially binds mostly nonproductively to four-way junctions, which does not require divalent metals, and subsequently cleaves the junctions by a mechanism dependent on a divalent cation and a particular topological conformer that is induced by the sequences at the mobile junctions. PMID- 8195152 TI - Topographical analysis of the plasma membrane-associated sucrose binding protein from soybean. AB - Plasma membranes of soybean cells actively engaged in sucrose transport have a sucrose binding protein (SBP) that does not appear to be an integral membrane protein. Experiments were undertaken to analyze the topographical association of this protein with the membrane. Treatment of purified plasma membrane vesicles with either 1 M KCl or KI released less than 35% of the sucrose binding protein from the membrane whereas treatment with either 4 M urea or 0.1 M Na2CO3, pH 11.5, disassociated between 50 and 70%, respectively, of this protein from the membrane. SDS, at either 0.5x, 1x, or 10x of its critical micelle concentration, effectively solubilized the sucrose binding protein. The nonionic detergents Triton X-100 and CHAPS, at either 0.5x, 1x, or 10x of their critical micelle concentration, solubilized between 65 and 75% of this protein. When either native plasma membrane-associated or in vitro-transcribed and -translated SBP were subjected to Triton X-114 phase separation, 80% partitioned into the detergent poor aqueous phase. These results indicate that the SBP is a peripheral membrane protein but also suggest that there is a population of this protein that is tethered to the membrane. PMID- 8195151 TI - Association of phosphatidylinositol 3-kinase with a specific sequence of the T cell receptor zeta chain is dependent on T cell activation. AB - The T cell antigen receptor (TCR).CD3 complex contains several distinct but related signal transduction modules termed "Reth motifs": one each in the cytoplasmic domains of CD3-gamma, -delta, and -epsilon chains and three in the CD3-zeta polypeptide (zeta A, zeta B, and zeta C). Cross-linking of individual motifs expressed in chimeric molecules leads to early and late T cell activation events. Although the activated T cell receptor associates with nonreceptor tyrosine kinases, the sites of interaction with kinases and other potential effector molecules have not been fully mapped. Here we show that phosphatidylinositol 3-kinase (PI 3-kinase) preferentially associated with the zeta chain membrane proximal motif zeta A. Maximal PI 3-kinase/zeta A association occurred following TCR.CD3 activation and was dependent upon phosphorylation of both tyrosine residues in zeta A. The association of PI 3-kinase was specific for zeta A and could be ranked zeta A >> zeta C > zeta B. Phosphorylation of the zeta A motif on tyrosine residues occurred in response to TCR.CD3 cross-linking in vivo. These results indicate that T cell activation leads to assembly of an intracellular signaling complex: recruitment of a tyrosine kinase, phosphorylation of zeta A, and association of PI 3-kinase. These data also support a model in which different Reth motifs of the TCR.CD3 complex recruit distinct signal transduction molecules. Thus, the subdomains of the T cell antigen receptor zeta chain may serve different roles during T cell maturation and antigen-driven activation. PMID- 8195153 TI - Dihydrofolate reductase of Drosophila. Cloning and expression of a gene with a rare transcript. AB - Traditionally, dihydrofolate reductase (DHFR) has been isolated and the corresponding gene cloned from drug-resistant cell lines which have amplified DHFR genes after selection. A Dhfr sequence has now been obtained by nested polymerase chain reaction (PCR) from Drosophila bearing a single gene copy. Using the PCR-amplified partial cDNA as a probe, Dhfr was cloned by screening a Drosophila genomic library. It consists of regulatory regions as well as a 599 nucleotide coding region with a single 50-base pair (bp) intron and encodes a protein of 182 amino acids. Previously we have shown that the enzyme has kinetic properties characteristic of both "prokaryotic" and "eukaryotic" DHFRs. Here we show that the organization of Drosophila Dhfr is strikingly different from its mammalian counterparts and most similar to that of mosquito. A 790-bp transcript was detected by Northern blot analysis, with a single transcription start site located 27 bp upstream of ATG codon. The Drosophila genome contains a single Dhfr copy at 89E and a selected cell line has not amplified the gene. Confirmation of the identity of this gene has been obtained by kinetic studies of recombinant DHFR over-expressed in Escherichia coli cells. PMID- 8195155 TI - Interleukin-1 beta maturation and release in response to ATP and nigericin. Evidence that potassium depletion mediated by these agents is a necessary and common feature of their activity. AB - Lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages produce large quantities of interleukin (IL)-1 beta but in the absence of a secondary stimulus little of this cytokine is proteolytically processed to its mature biologically active state and externalized. The potassium-proton ionophore nigericin and ATP are known to promote the maturation and release of IL-1 beta from LPS-stimulated cells. We investigated the mechanisms by which these agents act in an attempt to understand requirements of the post-translational processing. Like nigericin, the ionophores A204 and lasalocid induced the release and maturation of IL-1 beta. The electrogenic potassium ionophore valinomycin, however, did not stimulate these post-translational events. Addition of nigericin or lasalocid to LPS stimulated cells produced a rapid intracellular acidification; A204, however, did not alter pH, indicating that an acidification was not necessary for activation of IL-1 beta maturation. Macrophages treated with ATP became rounded and swollen, and after 30 min of treatment their appearance was comparable with cells treated with nigericin. Post-translational maturation and release of IL-1 beta began immediately after ATP addition. The majority of the 17-kDa mature IL-1 beta produced within the first 30 min of treatment was recovered extracellularly; in contrast, during this same time period the 35-kDa IL-1 beta precursor and the cytoplasmic marker enzyme lactate dehydrogenase and the lysosomal enzyme beta-N acetylglucosaminidase remained cell-associated. ATP, therefore, promoted both the proteolytic maturation of IL-1 beta and the release of the biologically active species in the absence of cell lysis. Longer incubations with ATP caused cytolysis as judged by the release of the cytoplasmic enzymes. ADP was less active than ATP at initiating the post-translational maturation and release of IL 1 beta and AMP, GTP, and UTP were totally inactive, ATP, nigericin, A204, and lasalocid promoted a rapid and complete loss of the potassium analog 86Rb+ from cells that were preloaded with this cation; valinomycin-treated cells released only a portion of the radiolabeled cation. Agents that promoted the maturation and release of IL-1 beta from LPS-stimulated macrophages, therefore, shared an ability to mobilize intracellular potassium. Macrophages treated with ATP or nigericin in medium that contained KCl rather than NaCl failed to proteolytically activate and to release IL-1 beta. These data suggest that ATP and nigericin induce a net decrease in intracellular levels of K+ which is necessary for activation of the post-translational maturation of IL-1 beta. PMID- 8195154 TI - Imaging of total intracellular calcium and calcium influx and efflux in individual resting and stimulated tumor mast cells using ion microscopy. AB - Ion microscopy was employed to investigate intracellular total calcium concentrations and calcium influx, and efflux in resting and antigen-stimulated tumor mast cells (RBL-2H3 cells). The nucleus, a perinuclear region which included the Golgi apparatus (Golgi region), and the remaining cytoplasm were spatially resolved with the Cameca IMS-3f ion microscope in cryogenically prepared cells. In resting cells the nucleus contained about 0.60 mM, the Golgi region about 1.2 mM, and the remaining cytoplasm about 1.0 mM total calcium. Antigen stimulation of rat basophilic leukemia cells resulted in a significant loading of calcium in all three cellular compartments. Antigen stimulation in the absence of extracellular calcium resulted in a significant loss of total calcium from all three intracellular compartments. Influx and efflux of calcium were measured simultaneously in resting and stimulated cells by using stable 44Ca in the extracellular solution, and by imaging mass 40 to determine the native intracellular calcium (40Ca) and mass 44 to localize the 44Ca that entered the cell from extracellular solution. After a 10-min incubation, 0.240 fmol of the total calcium per cell had been replaced with 44Ca, which amounts to about 33% of the total cell calcium. If antigen was present during this incubation there was an additional loss of 0.229 fmol of 40Ca and an added gain of 0.476 fmol of 44Ca per cell, which corresponds to a net increase in total intracellular calcium of 0.247 fmol. PMID- 8195156 TI - Structure of the human Na+/glucose cotransporter gene SGLT1. AB - Intestinal uptake of dietary glucose and galactose is mediated by the SGLT1 Na+/glucose cotransporter of the brush border. An SGLT1 missense mutation underlies hereditary glucose/galactose malabsorption, characterized by potentially fatal diarrhea; conversely, oral rehydration therapy exploits normal transport to alleviate life-threatening diarrhea of infectious origin. We have mapped the entire human SGLT1 Na+/glucose cotransporter gene from cosmid and lambda phage clones representing a genomic region of 112 kilobases. Transcription initiation occurred from a site 27 base pairs 3' of a TATAA sequence. All exon flanking regions were sequenced, and the entire 112-kilobase region mapped with four restriction enzymes. SGLT1 is comprised of 15 exons (spanning 72 kilobases); a possible evolutionary origin from a six-membrane-span ancestral precursor via a gene duplication event is suggested from comparison of exons against protein secondary structure and from sequence considerations. A new missense mutation in exon 1 causing glucose/galactose malabsorption is also described. This is the first Na(+)-dependent cotransporter gene structure reported. These data facilitate the search for new glucose/galactose malabsorption-related mutations in this important gene and provide a basis for future evolutionary comparisons with other Na(+)-dependent cotransporters. PMID- 8195157 TI - Mutagenesis of cardiac troponin I. Role of the unique NH2-terminal peptide in myofilament activation. AB - Phosphorylation of Ser residues in the NH2-terminal extension unique to cardiac troponin I (cTnI) is known to occur through protein kinase A and to alter myofilament Ca2+ activation (Robertson, S. P., Johnson, J. D., Holroyde, M. J., Kranias, E. G., Potter, J. D., and Solaro, R. J. (1982) J. Biol. Chem. 257, 260 263). Yet, how the NH2-terminal extension may itself affect thin filament Ca2+ signaling is unknown. To approach this question we have used molecular cloning, mutagenesis, and bacterial synthesis of a full-length cTnI and a truncated mutant (cTnI/NH2) missing the 32 amino acids. Using reconstituted preparations we could show no differences between cTnI and cTnI/NH2 either in inhibition of actomyosin ATPase activity, in Ca(2+)-reversible inhibitory activity, or in the relation between pCa and Ca2+ binding to the regulatory site of cTnC at either pH 7.0 or 6.5. There were also no significant differences at either pH in the pCa-MgATPase activity relation of myofibrils into which the various species of TnI has been exchanged. Our results indicate: 1) that phosphorylation most likely induces a new state of TnI activity rather than altering an intrinsic effect of the NH2 terminal peptide on Ca2+ activation; and 2) that domains outside the NH2-terminal extension are important with regard to differences in effects of acidic pH on Ca2+ activation on cardiac and skeletal myofilaments. PMID- 8195158 TI - Cloning and expression of Ole e I, the major allergen from olive tree pollen. Polymorphism analysis and tissue specificity. AB - Ole e I, the major allergen from the olive tree (Olea europaea), is one of the main causes of allergy in Mediterranean countries and some areas of North America. The cloning and sequencing of several cDNAs coding for the olive allergen have been achieved. cDNA has been synthesized from total pollen RNA and amplified by using the polymerase chain reaction. The nucleotide sequence data demonstrate the existence of microheterogeneities in at least 37 positions out of the 145 amino acids of Ole e I, thus explaining the high degree of polymorphism exhibited by the natural protein. One of the sequenced cDNAs encoding a full length isoform was inserted into the plasmid vector pGEX-2T and overexpressed. The recombinant Ole e I has been produced in Escherichia coli as a fusion protein with glutathione S-transferase of Schistosoma japonicum. This chimeric protein was purified by affinity chromatography on a glutathione-Sepharose 4B column and digested with thrombin to release the recombinant allergen. Both the fusion protein and the recombinant Ole e I were recognized in Western blot analysis by rabbit polyclonal and mouse monoclonal antisera raised against native Ole e I as well as by the IgE of olive pollen-sensitive human sera. This indicates that the recombinant production of individual isoforms may be useful for the improvement of reagents to be used in diagnosis and therapy of IgE-mediated disorders. In addition, Ole e I mRNA has been observed to be pollen-specific as shown in a Northern blot analysis. PMID- 8195159 TI - Cytoplasmic metallothionein overexpression protects NIH 3T3 cells from tert-butyl hydroperoxide toxicity. AB - Metallothioneins (MT) are ubiquitous low molecular weight metal-binding proteins that may act as antioxidants. We examined the sensitivity of NIH 3T3 cells transfected with a plasmid containing mouse metallothionein-I gene (NIH3T3/MT) to the membrane permeant oxidant, tert-butyl hydroperoxide (tBH). NIH3T3/MT cells had a 4-fold increase in intracellular metallothionein as compared to cells transfected with a plasmid containing an inverted gene (NIH3T3/TM). Newly expressed metallothionein appeared to be localized to the cytoplasm as determined by immunofluorescence and confocal microscopy. NIH3T3/MT cells were 6 times more resistant than NIH3T3/TM cells to the cytotoxic effects of tBH. The antioxidant activity of NIH3T3/MT cells was greater than NIH3T3/TM cells, since exposure to tBH resulted in significantly less: (a) thiobarbituric acid-reactive substances and (b) fluorescence after loading cells with the oxidant-sensitive dye, 2'7' dichlorodihydrofluorescein diacetate. Furthermore, homogenates of NIH3T3/MT cells were more capable of scavenging in vitro generated phenoxyl radicals as quantified by electron spin resonance detection. In contrast, overexpression of cytoplasmic MT did not protect against tBH-induced DNA damage, suggesting that subcellular location of MT is important for its function and that DNA damage is not a key determinant of cytotoxicity. These data provide direct support for an antioxidant role for MT, since physiologically relevant elevations in cytoplasmic MT interfere with tBH-induced cytotoxic peroxidation. PMID- 8195160 TI - A protein which binds preferentially to single-stranded core sequence of autonomously replicating sequence is essential for respiratory function in mitochondrial of Saccharomyces cerevisiae. AB - From yeast nuclear extract, we have identified several DNA-protein complexes using the T-rich strand of core consensus sequence of autonomously replicating sequence by gel shift assay. One of them showed preferential binding to the T rich sequence of the DNA. We have partially purified a protein constituent of this complex and cloned its gene. The gene has an open reading frame encoding a protein of 380 amino acids (M(r) = 42,100) which is processed to a mature protein of 371 amino acids (M(r) = 40,900). The protein has neither significant amino acid homology with any previously reported proteins nor characteristic motifs. A putative HAP2/HAP3/HAP4 binding sequence was found at about 1 kilobase upstream of the gene. Disruption of the chromosomal gene revealed that the gene was neither essential for cell viability nor involved in DNA replication, but was essential for mitochondrial respiratory function. We therefore named the gene MRF1 for mitochondrial respiratory function 1. In a mrf1 null mutant the absorption spectra of cytochromes b, a, and a3 were undetectable, although mitochondrial DNA and protein synthesis in mitochondria were intact. Antibodies against MRF1 detected the antigen localized predominantly in the nucleus in vivo. These results suggest that MRF1 is a transcriptional regulatory protein of some genes whose products are necessary for the functional assembly of mitochondrial respiratory proteins. PMID- 8195161 TI - Spatial resolution of the primary beta-amyloidogenic process induced in postischemic hippocampus. AB - Proteolytic modifications of amyloid precursor protein (APP) play key roles in the development of Alzheimer's disease. However, each specific in vivo process has not yet been fully resolved in spatial terms because the orthodox approach employing electrophoretic analysis requires homogenization of samples and thus provides limited information on the localization of the process. To acquire such spatial information for the primary process involved in beta-amyloidogenesis, we have designed and developed a novel antibody exclusively specific to APP fragments possessing the exact amino terminus of the major beta-amyloid (A beta) peptide. Use of this antibody revealed that cleavage of APP at the amino terminal position of the A beta sequence is a normal steady-state process in gerbil hippocampus. Furthermore, nonfatal transient (10 min) forebrain ischemia followed by reperfusion enhanced the initial beta-amyloidogenic reaction mainly in pyramidal cells of CA1 sector and of dentate gyrus prior to and along with delayed neuronal degeneration. The APP fragments accumulated in cell bodies and dendrites of the neurons. These results suggest that beta-amyloidogenesis may involve a process that is also activated in postischemic brain and that ischemia like conditions may contribute to pathogenic A beta accumulation. PMID- 8195162 TI - Purification, characterization, and cDNA cloning of procathepsin L from the culture medium of NIH-Sape-4, an embryonic cell line of Sarcophaga peregrina (flesh fly), and its involvement in the differentiation of imaginal discs. AB - A cysteine proteinase that preferentially hydrolyzes carbobenzyloxy-Phe-Arg-MCA (MCA, methylcoumaryl-7-amide) was purified from the culture medium of NIH-Sape-4 cells. The molecular mass of this enzyme was easily changed from 50 to 35 kDa, without appreciable loss of enzyme activity. From the analysis of its cDNA, this enzyme was concluded to be a procathepsin L of Sarcophaga. Only procathepsin L was found in the medium, while the mature 35-kDa cathepsin L was found exclusively in the cells, indicating that the cells have a mechanism to secrete procathepsin L selectively. An antibody against procathepsin L was found to inhibit the differentiation of imaginal discs cultured in vitro in the presence of 20-hydroxyecdysone. In fact imaginal discs were shown to secrete procathepsin L into the culture medium. These results suggest that procathepsin L is an essential proteinase for differentiation of imaginal discs. Northern blotting analysis revealed that unfertilized eggs contain a significant amount of mRNA for the procathepsin L as a maternal mRNA. PMID- 8195163 TI - BSF1, a novel brain-specific DNA-binding protein recognizing a tandemly repeated purine DNA element in the GABAA receptor delta subunit gene. AB - The rat GABAA receptor delta subunit gene has been isolated and its promoter mapped to facilitate studies of neuron-specific gene transcription. The gene is transcribed from a single promoter with several clustered transcriptional initiation sites. The major start site maps to a prototype initiator sequence located in the center of a TATA-less CpG-rich island. Analysis of the 5'-flanking region of the GABAA receptor delta subunit gene revealed a novel tandemly repeated purine sequence element. Furthermore, gel retardation assays identified several tissue-specific and ubiquitous proteins that bind to this sequence. One of these factors, brain-specific factor (BSF) 1, was only observed in extracts from brain and was distinct from BETA and PAL, two DNA-binding proteins with similar purine-rich recognition sequences. The distribution of BSF1 in brain closely matched the expression pattern previously determined for the delta subunit mRNA, and its binding activity appeared simultaneously with GABAA receptor delta subunit mRNA during differentiation of cerebellar granule cells in vitro. Our data therefore suggest that BSF1 is a novel brain-specific and neuronal cell type-enriched factor possibly involved in differential transcription of the GABAA receptor delta subunit gene. PMID- 8195164 TI - A monoclonal antibody against oxidized lipoprotein recognizes foam cells in atherosclerotic lesions. Complex formation of oxidized phosphatidylcholines and polypeptides. AB - In this study we have used homogenates of human atheromatous plaque as immunogen to establish a murine monoclonal antibody which recognizes oxidized low density lipoprotein (LDL). This monoclonal antibody, FOH1a/DLH3, reacted with oxidized LDL, but enzyme-linked immunosorbent assay showed that it had no reaction with native, acetylated, or malonaldehyde-treated LDL. The antibody cross-reacted with oxidized high density lipoprotein, suggesting that specific sequences of the apolipoprotein B are not essential for antigen recognition by the antibody. Immunohistochemical analysis of thin paraffin sections from human coronary arteries showed that foam cells derived from macrophages in atherosclerotic lesions were heavily stained by this antibody. Several other structures in the lesions, including swollen collagen fibers, cellular debris in necrotic cores, and endothelial cells, were moderately stained. The epitope of this antibody was characterized by a model antigen-generating system using ferrous ion-induced peroxidation of lipids. When the total lipid fraction extracted from LDL was treated with the ferrous ion-induced peroxidation system, the reaction mixture was recognized by the antibody. Antigenic product(s) was produced only when phosphatidylcholine (PC) was treated with the ferrous ion-induced peroxidation, other lipids failed to react to the antibody. To investigate the possible formation of a complex of antigenic product with a polypeptide, a synthetic peptide and a rabbit antiserum against the peptide were used. Reaction mixture of ferrous ion-induced peroxidation of PC in the presence of the peptide was added to a microtiter well precoated with the monoclonal antibody FOH1a/DLH3. After washing, the peptide remaining in the well was detected with rabbit antiserum against the peptide, whereas no reactivity was observed when peptide alone was added to the well. Binding of the antigenic complex to the precoated monoclonal antibody was competed by oxidized PC produced in the absence of any polypeptide. We conclude that oxidized phospholipid product(s) is the epitope of the monoclonal antibody and that the oxidized phospholipid forms complexes with polypeptides. The antigenic materials are detected in foam cells in atherosclerotic lesions. PMID- 8195165 TI - Characterization of a novel cofilin isoform that is predominantly expressed in mammalian skeletal muscle. AB - Cofilin is an actin-modulating protein of 20 kDa, which is widely distributed throughout muscle and non-muscle cells. By means of immunoblotting combined with two-dimensional gel electrophoresis, we found that two cofilin variants, muscle type (M-type) and non-muscle type (NM-type), exist in mammals, while a single isoform exists in chickens. During in vitro myogenesis of mouse C2 cells, expression of the M-type cofilin was upregulated. To better understand the nature of the M-type cofilin, we cloned cDNAs encoding M-type cofilin from the cDNA library of C2 myotubes and determined the entire sequence. The deduced peptide sequence contained a nuclear localization signal and a putative actin-binding sequence as reported in NM-type cofilin. The sequence showed 81% identity in the amino acid residues with the mouse NM-type cofilin sequence and, interestingly, higher homology (96% identity) with that of chicken cofilin. The mRNA encoding M type cofilin, though it contains two variants that differ in the size of their 3' non-coding sequences, was detected predominantly in heart, skeletal muscle, C2 myotubes, and testis by Northern blotting, while the mRNA for NM-type cofilin was seen in a variety of non-muscle tissues. The presence of the muscle type isoform of cofilin strongly suggests that cofilin is deeply involved in the regulation of actin function not only in non-muscle cells but also in muscle cells. PMID- 8195166 TI - Identification of the IgG binding site of the human low affinity receptor for IgG Fc gamma RII. Enhancement and ablation of binding by site-directed mutagenesis. AB - Fc receptor-antibody interactions are key mechanisms through which antibody effector functions are mediated. The low affinity receptor for IgG, Fc gamma RII, is expressed on most hematopoietic cells, and through the binding of immune complexes mediates a large spectrum of biological responses vital for resistance to infection and the regulation of immunity. In this study the key residues of human Fc gamma RII involved in the interaction with IgG1 have been identified. Chimeric receptors composed of extracellular regions of Fc gamma RII and the Fc epsilon RI alpha chain have been used to localize the IgG1 binding site of Fc gamma RII to an 8-residue stretch in the second extracellular domain, Asn154 to Ser161. Site-directed mutagenesis of this region revealed that substitution of Ile155 or Gly156 with alanine ablated the binding of human and mouse IgG1, whereas replacement of Leu159, Phe160, or Ser161 with alanine enhanced binding. Molecular modeling has been used to generate a putative 3-dimensional model structure of the second extracellular domain of Fc gamma RII, suggesting that the binding site lies in an exposed loop region at the interface of domains 1 and 2. PMID- 8195167 TI - Regulation of synapsin I gene expression by the zinc finger transcription factor zif268/egr-1. AB - zif268/egr-1 is an immediate early response gene that is involved in regulation of growth and differentiation. Its mRNA encodes a sequence-specific transcriptional activator containing three zinc fingers that act as the DNA binding domain. Although zif268/egr-1 is expressed in the nervous system during neuronal excitation, no target gene has yet been identified. Here we report that the zif268/egr-1 protein bound in vitro to two sites in the proximal regulatory region of the human synapsin I gene. The zif268/egr-1 protein was also shown to stimulate transcription from this control region in transactivation assays. Additionally, the presence of a putative neural-restrictive silencer element next to one of the zif268/egr-1-binding sites interfered with transactivation in a tissue-independent manner. An analysis of the temporal expression pattern of zif268/egr-1 and synapsin I during neuronal differentiation of P19 embryonal carcinoma cells revealed that zif268/egr-1 mRNA was induced on day 5 and synapsin I mRNA on day 8 after retinoic acid treatment. From this data we conclude that the synapsin I gene is a target of the zif268 transcription factor; however, intermediate factors may also be involved in the activation. PMID- 8195168 TI - Purification and characterization of a 20-kDa protein that is highly homologous to alpha B crystallin. AB - A 20-kDa protein (p20) that had internal amino acid sequences highly similar to those of alpha B crystallin was purified from rat and human skeletal muscle. p20 co-eluted with alpha B crystallin and HSP27/28 during column chromatography on DEAE-Sepharose and on Bio-Gel A-5m. p20 was separated from alpha B crystallin and HSP27/28 and was resolved into two fractions, a minor first peak and a major second peak, by column chromatography on S-Sepharose in the presence of 7 M urea. During chromatography on a column of Superdex 75pg, even in the presence of 7 M urea, p20 in the second peak was eluted as aggregates near the exclusion volume of the column, whereas p20 in the first peak was eluted in fractions that corresponded to a lower molecular mass. Further chromatography on a TSK-SP-5PW column yielded pure preparations of each of the two forms of rat and human p20. The fragmentation patterns of the two forms of the respective p20 proteins generated by digestion with endoproteinase Asp-N were identical. The primary structures of rat and human p20, determined with an NH2-terminal sequenator, were highly homologous to those of alpha B crystallin and HSP27/28. p20 was present in all rat tissues examined and at high levels (> 1 micrograms/mg protein) in the soleus muscle, heart, and diaphragm, as are alpha B crystallin and HSP27. Centrifugation on sucrose density gradients allowed detection of the aggregated form and the small form of p20, as well as of HSP27, in extracts of rat muscle tissues. During heating at 45 degrees C of tissue in vitro, p20 in rat diaphragm was redistributed from the cytoplasm to the insoluble fraction, and dissociation of the aggregated p20 to the small form was enhanced. These results suggest that p20 is related to stress proteins. PMID- 8195169 TI - Specific recognition of the blk promoter by the B-lymphoid transcription factor B cell-specific activator protein. AB - Several genes of the src family encode protein-tyrosine kinases that associate with the B-cell antigen receptor complex and are activated upon receptor cross linking, including blk, lyn, and fyn. The blk gene is the only member of this family whose expression is restricted to B-lymphoid cells. In the B lineage, blk is developmentally regulated: blk transcripts are first detected in pro-B-cells and persist until the differentiation of mature B-cells to plasma cells. We have found that the blk promoter is a target for a specific DNA-binding protein whose activity in B-lymphoid cell lines is positively correlated with blk expression. By three criteria, we have identified this DNA-binding protein as the transcription factor B-cell-specific activator protein (BSAP): 1) oligonucleotides containing known BSAP recognition sites were found to compete specifically with blk for binding to the protein detected in B-lymphoid extracts; 2) authentic BSAP was shown to bind the same site within the blk promoter as the protein identified in B-lymphoid extracts; and 3) the specific DNA-protein complex formed in B-lymphoid extracts was shown to react with an anti-BSAP antiserum. BSAP has been implicated previously in the transcriptional regulation of CD19, whose pattern of expression in B-cell development coincides with that of blk. These observations, and the correlation between expression of BSAP and expression of blk, suggest that BSAP is a positive regulator of blk transcription. PMID- 8195170 TI - Yeast mitochondria lacking the two import receptors Mas20p and Mas70p can efficiently and specifically import precursor proteins. AB - Mas20p and Mas70p are integral proteins of the yeast mitochondrial outer membrane that appear to function as receptors for precursor proteins imported from the cytosol. Loss of either receptor alone does not block import or kill the cells, but deletion of Mas20p causes loss of respiration (Ramage, L., Junne, T., Hahne, K., Lithgow, T., and Schatz, G. (1993) EMBO J. 12, 4115-4123). Here we show that this respiratory deficiency is only temporary; given time to adapt, virtually all cells lacking MAS20p regain respiration without regaining MAS20p. The respiratory defect can also be suppressed (at a frequency of about 10(-6)) by a dominant mutation of a single nuclear gene. The suppressed cells, unlike the unsuppressed ones, tolerate disruption of the MAS70 gene. The resulting double disruptants lack both Mas20p and Mas70p, yet are viable and able to respire. Protein import into mitochondria isolated from these cells is efficient, specific, and highly sensitive to protease treatment. We propose that at least one additional mitochondrial surface protein can function as a protein import receptor and that the activity of this component is up-regulated by a stress response or by an extragenic suppressor. PMID- 8195171 TI - Direct interaction between Shc and the platelet-derived growth factor beta receptor. AB - The Src homology 2 (SH2) domain-containing Shc proteins p52shc and p46shc become phosphorylated upon activation of several tyrosine kinases and are implicated in mitogenic signal transduction. Ligand stimulation of the platelet-derived growth factor (PDGF) beta-receptor leads to autophosphorylation of tyrosine residues, which is known to mediate interactions with several SH2 domain-containing signaling molecules. In this study, we have characterized the interaction between the PDGF beta-receptor and Shc. PDGF beta-receptor coprecipitation in Shc immunoprecipitates was dependent on stimulation with PDGF-BB. The Shc SH2 domain expressed as a bacterial fusion protein bound the autophosphorylated PDGF beta receptor. Moreover, the Shc SH2 domain could bind the autophosphorylated purified baculovirus-expressed PDGF beta-receptor intracellular domain, which indicates a direct association of Shc with the PDGF beta-receptor. Activation of the PDGF beta-receptor induced the preferential phosphorylation of p52shc. Tyrosine phosphorylated Shc, in turn, formed a complex with the signaling molecule Grb2. Synthetic peptide analysis revealed that certain autophosphorylation sites in the PDGF beta-receptor (Tyr-579, Tyr-740, Tyr-751, and Tyr-771) were able to mediate the specific binding of the Shc SH2 domain as well as intact Shc proteins. A mutant PDGF beta-receptor in which Tyr-579 was replaced with phenylalanine showed 40% impaired association of Shc in vivo, but phosphorylation of Shc proteins was not affected. We conclude that multiple autophosphorylation sites in the PDGF beta-receptor are responsible for the binding of Shc. This is in contrast to previously characterized interactions between the PDGF beta-receptor and SH2 domain-containing proteins, which generally involve one high affinity binding site in the receptor. PMID- 8195172 TI - INO2 and INO4 gene products, positive regulators of phospholipid biosynthesis in Saccharomyces cerevisiae, form a complex that binds to the INO1 promoter. AB - The INO4 gene encodes a protein required for derepression of a number of structural genes encoding enzymes involved in phospholipid biosynthesis in the yeast Saccharomyces cerevisiae. Ino4p shows structural similarity to the basic helix-loop-helix (bHLH) family of regulatory proteins (Hoshizaki, D. K., Hill, J. E., and Henry, S. A. (1990) J. Biol Chem. 265, 4736-4745). In this report we demonstrate that Ino4p translated in vitro forms a complex with Ino2p, another positive regulator of phospholipid biosynthesis that contains a bHLH domain. The Ino2p.Ino4p complex binds to a fragment of the INO1 promoter containing two copies of the consensus binding site for the bHLH family of proteins. The complex formed when this DNA fragment is incubated with in vitro translated Ino2p and Ino4p is identical in mobility to the complex formed when this DNA fragment is incubated with whole cell extracts. The binding of DNA by the Ino2p.Ino4p complex is competed by an oligonucleotide containing the consensus binding sequence for bHLH proteins. Neither Ino2p nor Ino4p translated alone is capable of forming a complex with the INO1 promoter fragment. The two products, translated separately and mixed, show only reduced capability to form a complex compared with cotranslated proteins. Immunoprecipitation experiments demonstrate that Ino2p and Ino4p interact in the absence of DNA. Ino2p and Ino4p are, thus, both necessary and sufficient for formation of a complex with the INO1 promoter. PMID- 8195173 TI - A soluble secretory protein of the intracellular parasite Toxoplasma gondii associates with the parasitophorous vacuole membrane through hydrophobic interactions. AB - The obligate intracellular parasite Toxoplasma gondii resides within a specialized, nonfusogenic vacuole termed the parasitophorous vacuole. We are exploring the hypothesis that parasite proteins contained in dense core granules and secreted into the vacuole after cell invasion contribute to the modification of the parasitophorous vacuole membrane (PVM). The dense granule protein GRA3 associates preferentially with the PVM. Here we show that GRA3 liberated from dense granules is a soluble protein. Following secretion, one-third or more of GRA3 in the parasitophorous vacuole becomes stably associated with the vacuole membrane as judged by sucrose flotation gradients and Triton X-114 phase partitioning experiments. GRA3 cannot be removed from the membrane by extraction with sodium carbonate at pH 11.0, nor can it be labeled in infected cells with [1 14C]acetate. In sucrose velocity sedimentation gradients, GRA3 from vacuolar membranes solubilized in Triton X-100 sediments as an oligomer. Membrane associated GRA3 cross-links to itself, migrating as a ladder of bands in SDS polyacrylamide gel electrophoresis. No other parasite or cell proteins co precipitate with cross-linked GRA3. We conclude that a portion of GRA3 secreted from the parasite as a soluble protein directly inserts into the vacuole membrane in an oligomeric form. This is the first report in Toxoplasma or related parasites of a protein which inserts into the vacuole membrane for some purpose other than to lyse that membrane. PMID- 8195174 TI - Ouabain-resistant OR6 cells express the murine alpha 1-subunit of the Na,K-ATPase with a T797-I797 substitution. AB - Introduction of the murine "ouabain resistance gene" (Levenson, R., Racaniello, V., Albritton, L., and Housman, D. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 1489 1493) into African Green monkey CV1 cells reportedly resulted in one cell line, OR6 cells, which was found to be resistant to > 1 mM ouabain (English, L., Epstein, J., Cantley, L., Housman, D., and Levenson, R. (1985) J. Biol. Chem. 260, 1114-1119). The present analysis of the genomic sequence of the alpha 1 subunit of the Na,K-ATPase from OR6 cells reveals copies of the gene for the murine and human alpha 1-subunit of the Na,K-ATPase and not the monkey gene, indicating that the cells have been misidentified. The sequence of the murine alpha 1-subunit from OR6 cells reveals a single point mutation encoding a T797 I797 amino acid substitution at the H6 membrane border. Transfection of CV1 cells with a murine alpha 1 cDNA containing this point mutation resulted in cells with an IC50 for ouabain of approximately 5 mM. These data show that the super ouabain resistant phenotype of OR6 cells is due to expression of a mutant form of the murine alpha 1-subunit of the sodium pump (rather than the ouabain resistance gene) and further support the recent data suggesting involvement of the H5-H6 domain in ouabain inhibition of the sodium pump. PMID- 8195175 TI - Efficient anchoring of RNA polymerase in Escherichia coli during coupled transcription-translation of genes encoding integral inner membrane polypeptides. AB - While it has been known that supercoiling of the DNA template can be induced by transcription, the mechanism and the efficiency of this process in vivo is not fully understood. We report here that transcription of genes encoding 16 S rRNA, a stable RNA species, or cytoplasmic polypeptides leads to very little or no detectable DNA supercoiling even under the optimum conditions in Escherichia coli. This indicates that hydrodynamic drag on the transcription complex (including RNA polymerase, nascent RNA, ribosomes, and nascent polypeptides) is not sufficient to anchor RNA polymerase during coupled transcription-translation. On the other hand, transcription of membrane-associated genes encoding integral inner membrane or exported periplasmic polypeptides leads to apparent DNA supercoiling. Transcription of genes encoding integral inner membrane polypeptides leads to significantly greater anchoring of RNA polymerase than does transcription of genes encoding periplasmic polypeptides. This may reflect differences in the coupling of transcription-translation with membrane association during expression of these two classes of polypeptides. Evidence is further presented to suggest that the anchoring of RNA polymerase is probably achieved through the interaction of nascent polypeptides with the cytoplasmic surface of the inner membrane during coupled transcription-translation. Moreover, transcriptions of a membrane-associated gene can, under certain circumstances, induce topological anchoring of an RNA polymerase transcribing a neighboring gene that ordinarily is not membrane-associated. Finally, the potential biological consequences of our findings are discussed. PMID- 8195176 TI - SH2-containing phosphotyrosine phosphatase Syp is a target of p210bcr-abl tyrosine kinase. AB - The phosphorylation of proteins at tyrosine residues is critical in cellular signal transduction and neoplastic transformation. These mechanisms are regulated by the activities of both protein-tyrosine kinases and protein-tyrosine phosphatases. Recent studies have identified a novel protein-tyrosine phosphatase, termed Syp, that is widely expressed in various tissues. Syp encodes a cytoplasmic phosphatase that contains two Src homology 2 (SH2) domains. Since SH2 domains have been shown to target the association of signal-transducing molecules to activated tyrosine kinases, experiments were performed to determine whether Syp might form specific complexes with p210bcr-abl, a fusion protein believed to be involved in the pathogenesis of chronic myelogenous leukemia and, thus, possibly alter or mediate p210bcr-abl tyrosine kinase activity. We found that Syp was highly and constitutively tyrosine phosphorylated in three different murine cell lines transfected with a p210bcr-abl expression vector. Furthermore, p210bcr-abl, Syp, and Grb2 formed stable complexes in BCR-ABL-expressing cells. Complex formation between p210bcr-abl and Syp was mediated in vitro by the NH2 terminal SH2 domain of Syp. Last, p210bcr-abl tyrosine kinase was effectively dephosphorylated by Syp in vitro. These results suggest an interaction between Syp and BCR-ABL protein, which might play a role in cellular transformation of BCR-ABL. PMID- 8195177 TI - Membrane association and oligomeric organization of the alpha and beta subunits of mouse meprin A. AB - Meprins are oligomeric cell surface metalloproteinases of the "astacin family." They consist of two types of subunits (alpha and beta), which are evolutionarily related and whose cDNA sequences predict a similar domain structure. The present work shows that reducing agents solubilized meprin alpha subunits (approximately 90%), but not beta subunits, from mouse kidney brush border membranes. In addition, immunoblotting of membranes or purified meprins with an antibody raised to the alpha subunit epidermal growth factor-like domain, predicted to be near the COOH terminus from the cDNA-deduced amino acid sequence, indicated that this domain is not present in the mature alpha subunit. By contrast, an epitope predicted to be near the COOH terminus of the beta subunit was present in the mature form of beta. When meprins were solubilized from brush border membranes by papain, the size of the alpha subunit (approximately 90 kDa) did not change, while the beta subunit decreased from 110 to 90 kDa with concomitant loss of the COOH-terminal epitope. These data indicate that beta is a type I transmembrane protein, while alpha does not transverse the membrane and its association is dependent on disulfide bonds. The oligomeric organization of purified meprin A (EC 3.4.24.18), examined by sedimentation equilibrium analysis and native gradient gel electrophoresis, is that of disulfide-bridged dimers which aggregate noncovalently to form higher molecular weight complexes, predominantly tetramers. Western blotting of ICR kidney brush border membrane proteins identified alpha 2 homodimers and alpha beta heterodimers. Treatment of mouse or rat kidney brush border membranes with 7 M urea solubilized alpha 2, but not alpha beta dimers. Thus, the mature alpha subunit exists in alpha 2 and alpha beta disulfide-linked dimers which form tetramers, and the alpha 2 homodimers associate with the membrane through noncovalent interactions with alpha beta. PMID- 8195178 TI - Expression of the synaptic vesicle proteins VAMPs/synaptobrevins 1 and 2 in non neural tissues. AB - The VAMPs/synaptobrevins (Vp/Sybs) are small integral membrane proteins. Two isoforms, Vp/Syb 1 and Vp/Syb 2, are considered to be specific to neural tissue. They are associated with synaptic vesicles and are believed to play an important role in neurotransmitter release. A third isoform, cellubrevin, has recently been found in non-neural tissues. We now report that the distribution of Vp/Syb 1 and Vp/Syb 2 is wider than previously thought. RNA transcripts for both Vp/Syb 1 and Vp/Syb 2 were found in rat skeletal muscle and in several other rat non-neural tissues, and antibodies specific for Vp/Syb 2 detected a protein in the endoplasmic reticulum-Golgi area of skeletal muscle. Thus Vp/Sybs 1 and 2 are not restricted to the nervous system but appear to be co-expressed with cellubrevin in many different tissues. This redundancy of Vp/Sybs in a single cell may be required to control the specificity of vesicle-target interaction in the several pathways of intracellular vesicle traffic that are operative within each cell. PMID- 8195179 TI - GTP-dependent binding of the antiproliferative agent didemnin to elongation factor 1 alpha. AB - The marine natural product, didemnin B, is a 7-amino acid, cyclic depsipeptide that inhibits G1 cell cycle progression at nanomolar concentrations by undefined mechanisms. It has been reported to exhibit immunosuppressive activities in animals and is undergoing clinical trials as a potential antineoplastic drug. In addition, at higher concentrations, didemnin B has been shown to inhibit in vivo and in vitro protein synthesis. However, the mechanisms by which inhibition is achieved are unknown. To investigate didemnin's various modes of action, an affinity column was synthesized and used to purify didemnin-binding proteins. The major retained protein was the 49-kDa guanine nucleotide-binding elongation factor, EF-1 alpha, which was identified by peptide sequence analysis. Moreover, didemnin binds EF-1 alpha only in the presence of GTP but does not inhibit the GTPase activity of EF-1 alpha. Therefore, EF-1 alpha is likely to be the intracellular target responsible for didemnin B's ability to inhibit protein synthesis. Furthermore, this specificity of didemnin affinity for the GTP-bound conformation of a guanine nucleotide-binding protein with homology to the Ras superfamily suggests a possible mode of action for didemnin's antiproliferative activity. PMID- 8195180 TI - Ultrastructural localization of CTP:phosphoethanolamine cytidylyltransferase in rat liver. AB - CTP:phosphoethanolamine cytidylyltransferase (EC 2.7.7.14) (ethanolamine phosphate cytidylyltransferase, ET) was recently purified to homogeneity from a post-microsomal supernatant of rat liver and subsequently used to raise a polyclonal antibody against the enzyme in rabbits (Vermeulen, P. S., Tijburg, L. B. M., Geelen, M. J. H., and van Golde, L. M. G. (1993) J. Biol. Chem 268, 7458 7464). In the present study, we used the affinity-purified antibody against ET for ultrastructural immunogold labeling studies on rat liver cryosections. Single label experiments clearly demonstrated that ET label was not randomly distributed in hepatocytes. The ET label was concentrated in areas that contained cisternae of the rough endoplasmic reticulum, whereas other cellular organelles (nuclei, mitochondria, and peroxisomes) were only marginally labeled for ET. Double-label experiments for ET and established markers for either soluble or integral endoplasmic reticulum proteins suggested a bimodal distribution of ET between the RER cisternae and the cytosolic space. Complementary single-label studies for ET and the soluble marker protein showed that the fraction of ET label that was present on RER cisternae was significantly greater than that of the soluble marker, supporting the idea of an uneven distribution. These immunoelectron microscopy studies strongly suggest that the cellular organization of ET differs considerably from that reported recently for the corresponding enzyme in the CDP choline pathway, CTP:phosphocholine cytidylyltransferase (Wang, Y., Sweiter, T. D., Weinhold, P. A., and Kent, C. (1993) J. Biol. Chem. 268, 5899-5904). PMID- 8195181 TI - The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. AB - The metabolism of the anticonvulsant drug mephenytoin exhibits a genetic polymorphism in humans, with the poor metabolizer trait being inherited in an autosomal recessive fashion. There are large interracial differences in the frequency of the poor metabolizer phenotype, with Oriental populations having a 5 fold greater frequency compared to Caucasians. Impaired metabolism of mephenytoin and a number of other currently used drugs results from a defect in a cytochrome P450 enzyme recently identified as CYP2C19. Attempts over the past decade to define the molecular genetic basis of the polymorphism have, however, been unsuccessful. We now report that the principal defect in poor metabolizers is a single base pair (G-->A) mutation in exon 5 of CYP2C19, which creates an aberrant splice site. This change alters the reading frame of the mRNA starting with amino acid 215 and produces a premature stop codon 20 amino acids downstream, which results in a truncated, non-functional protein. We further demonstrate that 7/10 Caucasian and 10/17 Japanese poor metabolizers are homozygous for this defect, indicating that this is the major defect responsible for the poor metabolizer phenotype. Finally, the familial inheritance of the deficient allele was found to be concordant with that of the phenotypic trait. PMID- 8195182 TI - p21 Ras as a governor of global gene expression. AB - The molecular mechanisms for signaling by receptor serine/threonine kinases are incompletely understood. To test the potential involvement of p21 H-Ras proteins in signal transduction for type beta transforming growth factors (TGF beta), TGF beta-responsive and constitutive reporter genes were cotransfected into cardiac myocytes and mink lung epithelial cells, with dominant inhibitory (Asn-17) or activated (Arg-12) Ras expression vectors. Asn-17 Ras inhibited both TGF beta dependent and basal expression of inducible promoters (skeletal alpha-actin and plasminogen activator inhibitor-1), with equivalent dose-response relations. All seven reporter constructs were comparably sensitive to down-regulation by Asn-17 Ras, including those driven by nominally constitutive viral control regions or a TATA-less initiator element. All constructs were up-regulated by Arg-12 Ras more variably. Wild-type Ras had intermediate effects and could rescue a minimal thymidine kinase promoter from inhibition by dominant negative Ras. Thus, a Ras dependent event is required for efficient expression of an unexpectedly global or inclusive set of genes. PMID- 8195183 TI - Rab-GDI presents functional Rab9 to the intracellular transport machinery and contributes selectivity to Rab9 membrane recruitment. AB - Rab proteins occur in the cytosol bound to Rab-GDP dissociation inhibitor (GDI). We demonstrate here that cytosolic complexes of Rab9 bound to GDI represent a functional pool of Rab9 protein that can be utilized for transport from late endosomes to the trans Golgi network in vitro. Immunodepletion of GDI and Rab proteins bound to GDI led to the loss of cytosol activity; readdition of pure Rab9-GDI complexes fully restored cytosol activity. Delipidated serum albumin could solubilize prenylated Rab9 protein, but unlike Rab9-GDI complexes, Rab9 serum albumin complexes led to indiscriminate membrane association of Rab9 protein. Rab9 delivered to membranes by serum albumin was functional, but GDI increased the efficiency of Rab9 utilization, presumably because it suppressed Rab9 protein mistargeting. Finally, GDI inhibited transport of proteins from late endosomes to the trans Golgi network, likely because of its capacity to inhibit the membrane recruitment of cytosolic Rab9. These experiments show that GDI contributes to the selectivity of Rab9 membrane recruitment and presents functional Rab9 to the endosome-trans Golgi network transport machinery. PMID- 8195184 TI - Interaction of mitochondrial F1-ATPase with trinitrophenyl derivatives of ATP and ADP. Participation of third catalytic site and role of Mg2+ in enzyme inactivation. AB - Relatively high ATP concentrations show an unexpected lack of inhibition of the hydrolysis of low concentrations of trinitrophenyl ATP (TNP-ATP) by mitochondrial F1-ATPase. In striking contrast low TNP-ATP concentrations markedly inhibit the hydrolysis of much higher ATP concentrations. The three catalytic sites undergoing sequential conformational changes have different conformations at any instant of catalysis, and only two need to be filled for rapid, steady-state ATP hydrolysis. The remaining site has low affinity for ATP (Kd 2 mM) but about 10(4) greater affinity for TNP-ATP (Km and Kd about 0.2 microM). Thus 500 microM ATP does not prevent binding of less than 1 microM TNP-ATP. As the site binding the TNP-ATP undergoes sequential conformational changes the TNP-ATP undergoes sequential conformational changes the TNP-ATP is hydrolyzed and products are released. The results give strong support to the view that all three catalytic sites proceed equivalently in ATP as well as TNP-ATP hydrolysis. The conformation that has the lowest affinity for ATP has over a 10-fold greater affinity for ADP (Kd 150 microM) and may be akin to the conformation to which ADP binds during net ATP synthesis by the ATP synthase. The recognition of these features was made possible by new information obtained from detailed studies of the interactions of Mg2+, TNP-ADP, TNP-ATP, ATP, and noncatalytic sites on initial and steady-state hydrolysis rates. PMID- 8195185 TI - Regulation of the erythroid Kruppel-like factor (EKLF) gene promoter by the erythroid transcription factor GATA-1. AB - Erythroid Kruppel-like factor (EKLF) is an erythroid-specific transcription factor that binds a CACCC motif found in the human beta-globin gene promoter. We have studied the promoter of the EKLF gene and identified binding sites for the transcription factors GATA-1 and CCAAT-binding Protein 1 (CP1). We show that both types of binding sites are required for full activity, and that the GATA motif at -60 is essential. The EKLF promoter can be directly activated in nonerythroid cells in cotransfection experiments by forced expression of GATA-1. These results suggest that EKLF is dependent on GATA-1 for its expression and lies downstream of, or coincident with, GATA-1 in a regulatory hierarchy in erythroid development. PMID- 8195187 TI - Cloning and characterization of LAG1, a longevity-assurance gene in yeast. AB - The yeast Saccharomyces cerevisiae has a finite life span that is measured by the number of times the individual cell divides. The gene coding for one of several transcripts that are differentially expressed during the replicative life span has been cloned. The nucleotide sequence revealed an open reading frame capable of encoding a transmembrane protein of 411 amino acids that displays no significant similarities to any known proteins. Nevertheless, sequences similar to this gene were found in several mammals, including humans. The transcript levels decreased with replicative age of yeast cells. A gene deletion in haploid cells resulted in a pronounced increase (approximately 50%) in mean and in maximum life span. These results indicate that this gene, which we call LAG1, plays a role in determining yeast longevity. PMID- 8195186 TI - Control of cationic amino acid transport and retroviral receptor functions in a membrane protein family. AB - A partial cDNA sequence indicated that the T lymphocyte early-activation gene (Tea) encodes a protein related to the dual-function ecotropic retrovirus receptor/cationic amino acid transporter (ecoR/CAT1), and RNA blots suggested highest Tea expression in T lymphocytes and liver (MacLeod, C.L., Finley, K., Kakuda, D. Kozad, C.A., and Wilkinson, M.F. (1990) Mol. Cell. Biol. 7, 3663 3674). The sequence of full-length Tea cDNA from liver (3683 bases) predicts a 657-amino-acid protein (CAT2 alpha) with 12-14 transmembrane domains. A long (515 base) region with six initiation codons and termination codons precedes the translation start codon. The liver Tea cDNA is identical to Tea cDNA from T lymphocytes (encoding CAT2 beta) with the exception of an apparent alternatively spliced sequence encoding a hydrophilic loop of 43 amino acids. The liver specific sequence contains unique consensus sites for phosphorylation by cyclic AMP-dependent protein kinase and by protein kinase C. Injection of Xenopus oocytes with CAT2 alpha or CAT2 beta messenger RNA resulted in expression of Na(+)-independent cationic amino acid transport that was detected by current measurements under voltage-clamp. Although the amino acid sequences of the isoforms differ in only 21 of 43 residues with the majority of substitutions being conservative, the apparent affinity of CAT2 beta for arginine uptake was 70 fold higher than the CAT2 alpha isoform (Km 38 microM versus 2.7 mM). Neither isoform functioned as a receptor for ecotropic or amphotropic murine retroviruses. However, CAT1-CAT2 chimeric proteins that contain the first three putative extracellular loops of ecoR/CAT1 functioned as ecotropic receptors despite a diminished capacity to bind the viral envelope glycoprotein. The chimeric proteins also functioned as basic amino acid transporters with substrate affinities corresponding to the CAT2 isoform constituting the carboxyl-terminal portion. These results demonstrate that domains of these transporters can function in chimeric combinations to control viral receptor and transport functions. PMID- 8195188 TI - Transcriptional regulation of the human neuropeptide Y gene by nerve growth factor. AB - Neuropeptide Y (NPY) is the most ubiquitously expressed peptide in the mammalian nervous system. Transcription of the NPY gene in PC12 cells is regulated by a number of agents, including the neurotrophic peptide nerve growth factor (NGF). In this paper, we define the cis-acting promoter elements which respond to NGF and characterize the trans-acting factors which interact with these sequences. The NGF-responsive elements of the NPY gene lie between nucleotides -87 and -36. At least four proteins interact with this promoter region. One of these proteins interacts with a CT-rich sequence centered at position -51, which closely abuts a binding site for transcription factor AP-2 centered at position -63. Two newly characterized factors bind between positions -87 and -58. These proteins are expressed in a tissue-specific manner and, together with the other binding activities, modulate the transcriptional activity of the NPY gene. These results suggest that the concerted interplay of these proteins, in response to NGF, increases the transcriptional activity of the NPY gene. PMID- 8195189 TI - Structure and regulation of SDH3, the yeast gene encoding the cytochrome b560 subunit of respiratory complex II. AB - Using an expression library, we have isolated yeast genes activated in the presence of the yeast CCAAT box-binding protein HAP2. One of these genes, SDH3, encodes the cytochrome b560 subunit of respiratory complex II. The SDH3 protein contains three potential transmembrane domains and is more than 30% identical to bovine cytochrome b560 and to a mitochondrially encoded protein from Marchantia polymorpha. Disruption of SDH3 shows that this gene is required for growth on non fermentable carbon sources. Expression of SDH1, SDH3, and SDH4 is activated in the presence of the HAP2 transcriptional activator. PMID- 8195190 TI - Ligand-induced prostaglandin synthesis requires expression of the TIS10/PGS-2 prostaglandin synthase gene in murine fibroblasts and macrophages. AB - Phospholipase activation has been considered rate-limiting for ligand-stimulated prostaglandin (PG) synthesis. Constitutive prostaglandin synthase EC 1.14.99.1 (PGS-1) has been thought to convert arachidonate released following ligand stimulation to PGH2. However, a second prostaglandin synthase, TIS10/PGS-2, is inducible in many cell types, including fibroblasts and macrophages. We have used antisense oligonucleotide inhibition of TIS10/PGS-2 induction to investigate the role of this enzyme in ligand-induced prostaglandin production in fibroblasts and macrophages. Antisense TIS10/PGS-2 oligonucleotides block mitogen-induced prostaglandin production and TIS10/PGS-2 protein synthesis in both Swiss 3T3 cells and murine embryo fibroblast cultures, without inhibiting either constitutive PGS-1 activity or mitogen-stimulated arachidonic acid release. TIS10/PGS-2 antisense oligonucleotides also block production of PGE2 from endogenous arachidonate following endotoxin stimulation of both RAW 264.7 macrophage cells and murine peritoneal macrophages. In contrast, the constitutive prostaglandin synthase present in macrophages is unable to convert arachidonate released following endotoxin stimulation into prostaglandin. TIS10/PGS-2 expression is necessary for both mitogen-induced prostaglandin production in murine fibroblasts and endotoxin-induced prostaglandin synthesis in macrophages. PGS-1 present in these cells cannot utilize arachidonic acid released in response to mitogen or endotoxin stimulation. PMID- 8195191 TI - Structure of the novel heme adduct formed during the reaction of human hemoglobin with BrCCl3 in red cell lysates. AB - It was previously shown that the reductive debromination of BrCCl3 to trichloromethyl radical by human hemoglobin leads to formation of dissociable altered heme products, two of which are identical to those formed from myoglobin and one which is novel. In this study, we have elucidated the structure of this novel adduct with the use of mass spectrometry, as well as 1H and 13C NMR as a substitution product of a -C(Cl) = CCl2 moiety for a beta-hydrogen atom on the prosthetic heme's ring I vinyl group. From studies with the use of 13C-enriched BrCCl3, it was determined that the added carbon atoms were derived from 2 eq of BrCCl3. A mechanism that involves multiple reductive events and a radical cation heme intermediate is proposed. Consistent with this mechanism, cellular reductants were found to selectively enhance the amount of this novel dissociable heme adduct. These studies reveal fine differences between myoglobin and hemoglobin in the accessibility of reactive intermediates to the ring I vinyl group, as well as the potential importance of cellular reductants on the course of heme alteration. PMID- 8195192 TI - 1-beta-D-Arabinofuranosylcytosine stimulates ceramide and diglyceride formation in HL-60 cells. AB - The effect of 1-beta-D-arabinofuranosylcytosine (ara-C) on phospholipid metabolism was investigated in HL-60 cells. Treatment of cells with ara-C resulted in a time- and dose-dependent increase in the mass of ceramide and diglyceride. When cells were treated with 10 microM ara-C, an increase in the mass of ceramide and diglyceride was detectable at 5 min and reached a plateau at 30 min with a 2-fold increase compared to control cells. Treatment of cells with 10 microM ara-C resulted in the activation of neutral sphingomyelinase with a peak at 30 min that represented a 2-fold increase in specific activity. ara-C also increased expression of the transcription factor NF-kappa B which is related to the control of monocyte differentiation. These findings suggest that ara-C activates phospholipid hydrolytic pathways to generate second messengers that control gene expression and differentiation in the HL-60 cell line. PMID- 8195193 TI - Mammalian topoisomerase I has base mismatch nicking activity. AB - The all-type nicking enzyme (ATE) from human HeLa cells or calf thymus can nick DNA at the first phosphodiester bond 5' to all 8 possible mismatched bases. The strand disparity of this nicking is influenced by the neighboring nucleotide sequences. After nicking, the ATE covalently binds to the 3' end of the DNA product to form a cleavable complex, whose formation is insensitive to camptothecin, a specific inhibitor of eukaryotic topoisomerase I (Topo-I). During the purification of ATE from calf thymus, a Mg(2+)-independent relaxation activity, characteristic of eukaryotic Topo-I, copurifies with the mismatch nicking activity. The ATE from calf thymus may be a breakdown product of Topo-I. N-terminal amino acid analysis indicates that one of the polypeptides with ATE activity contains the C-terminal portion of Topo-I. Moreover, active human Topo I, expressed as a fusion protein in Escherichia coli, is also capable of nicking all 8 base mispairs in the absence of Mg2+. This mismatch-specific nicking activity may be a novel property of the mammalian Topo-I. PMID- 8195194 TI - Binding of sugar ligands to Ca(2+)-dependent animal lectins. I. Analysis of mannose binding by site-directed mutagenesis and NMR. AB - The Ca(2+)-dependent carbohydrate-recognition domain (CRD) of rat serum mannose binding protein has been subjected to site-directed mutagenesis to determine the importance of individual residues in ligation of mannose and related sugars. The effects of the mutations were assessed by direct binding assays, competition binding studies, partial proteolysis, and NMR analysis of sugar-CRD titrations. As suggested by the crystal structure of the mannose-binding CRD complexed with oligosaccharide ligand, asparagine and glutamic acid residues that interact with hydroxyl groups 3 and 4 of the sugar, as well as with one of the two bound Ca2+, are critical for ligand binding. In addition, the beta-carbon of His189 contributes substantially to the binding affinity, apparently through a van der Waals contact with C-4 of the sugar ligand. van der Waals contacts between the imidazole ring of His189 and the 2 hydroxyl group of mannose, and between Ile207 and C-6 of mannose, observed in the crystal structure, contribute less to stability of the ligand complex. The effects of changes at positions 189 and 207 on the ability of the CRD to distinguish between alpha-and beta-methyl L fucosides suggest that fucose may bind in an alternative orientation compared to the arrangement originally proposed based on the mannose-CRD complex. PMID- 8195195 TI - Binding of sugar ligands to Ca(2+)-dependent animal lectins. II. Generation of high-affinity galactose binding by site-directed mutagenesis. AB - Changes have been introduced into the Ca(2+)-dependent carbohydrate-recognition domain (CRD) of rat serum mannose-binding protein by site-directed mutagenesis to model the binding sites of homologous galactose-binding CRDs. Binding assays reveal that galactose-binding activity nearly identical to that of the CRD from the asialoglycoprotein receptor can be introduced into the mannose-binding site by 3 single amino acid changes and insertion of a segment of 5 amino acids. Separate changes are required to establish high-affinity binding to galactose and create high selectivity by exclusion of mannose from the binding site. The mutagenesis studies and NMR analysis of sugar-CRD titrations demonstrate that an important component of high-affinity galactose binding is interaction between the B face of the sugar and tryptophan. The binding properties of the C-type CRD from the cartilage proteoglycan, aggrecan, can also be modeled based on the mannose binding CRD frame-work. This lower affinity binding site involves stacking of a phenylalanine residue against the sugar ligand. PMID- 8195196 TI - Characterization of Ca2+/calmodulin-dependent protein kinase IV. Role in transcriptional regulation. AB - We have characterized Ca2+/calmodulin-dependent protein kinase IV (CaM kinase IV), expressed using the baculovirus/Sf9 cell system, to assess its potential role in Ca2+-dependent transcriptional regulation. CaM kinase IV was strongly inhibited in vitro by KN-62, a specific CaM kinase inhibitor which suppresses Ca2+-dependent transcription of several genes, so we tested whether CaM kinase IV could stimulate transcription. Co-transfection of COS-1 cells by cDNA for CaM kinase IV gave 3-fold stimulation of a reporter gene expression, whereas co transfection with CaM kinase II gave no transcriptional stimulation. Since this transcriptional response was mediated by phosphorylation of cAMP responsive element-binding protein (CREB), we determined the kinetics and site specificities of CaM kinases IV and II for phosphorylating CREB in vitro. CaM kinases IV and II and cAMP kinase (protein kinase A) all had similar Km values for CREB (1-5 microns), but the Vmax of CaM kinase IV was 40-fold lower than those of CaM kinase II and protein kinase A. Although all three kinases phosphorylated Ser133 in CREB, CaM kinase II also gave equal phosphorylation of a second site which was not Ser98. The two CREB phosphorylation sites were separately 32P-labeled, and the abilities of protein phosphatases 1, 2A, and 2B (calcineurin) to dephosphorylate them were tested. Our results show that all three phosphatases could dephosphorylate both sites, and calcineurin was a stronger catalyst for dephosphorylating site 1 (Ser133) than for site 2. These results indicate that CaM kinase IV may be important in Ca2+-dependent transcriptional regulation through phosphorylation of Ser133 in CREB. The fact that CaM kinase II phosphorylates another site in addition to Ser133 in CREB raises the possibility that this second phosphorylation site may account for the suppressed phosphorylation site may account for the suppressed ability of CaM kinase II to enhance transcription through the CRE/CREB system. In addition multiple protein phosphatases, including calcineurin, may exert a modulatory effect on transcription depending on which site they dephosphorylate. PMID- 8195197 TI - Recognition of C-terminal amide groups by (serine) carboxypeptidase Y investigated by site-directed mutagenesis. AB - Serine carboxypeptidases have the ability to hydrolyze peptides as well as peptide amides. Previously, it has been demonstrated that Asn51 and Glu145 (in the protonated form) each donate a hydrogen bond to the alpha-carboxylate of peptide substrate. It is here demonstrated by characterization of carboxypeptidase Y derivatives, mutationally altered at positions 51 and 145, that the same groups are involved in the interaction with the C-terminal carboxyamide group of peptide amides. Asn51 donates a hydrogen bond to the C = O group of the substrate, and Glu145 (in the charged form) accepts one from the NH2 group of the substrate. Thus, the ionic state of Glu145 is different when peptides are hydrolyzed as compared with when peptide amides are hydrolyzed. This explains why Km for the hydrolysis of peptides increases with pH, whereas it remains constant for peptide amides. As a consequence, kcat/Km for the hydrolysis of peptide amides is higher than for the hydrolysis of peptides at pH > 8. At physiological pH, peptides and peptide amides are hydrolyzed with rates of the same order of magnitude; this is in accordance with reports describing that serine carboxypeptidases are involved in the degradation of biologically active peptide amides. PMID- 8195198 TI - The interferon-gamma receptor extracellular domain. Non-identical requirements for ligand binding and signaling. AB - The human interferon-gamma receptor (hIFN-gamma R) extracellular domain interacts in a species-specific manner with both its ligand and an accessory factor encoded on human chromosome 21. Mutant interferon-gamma receptors were constructed by homolog-scanning mutagenesis, replacing segments of the human extracellular domain with the corresponding murine sequence. Replacement of hIFN-gamma R amino acids 1-100, 100-132, 134-183, or 183-245 abolished binding to human interferon gamma (hIFN-gamma). However, replacement of hIFN-gamma R amino acids 134-209, 183 209, 134-153, 153-167, or 167-183 or deletion of residues 156-165 affected hIFN gamma binding only partially or not at all. Receptors that bound hIFN-gamma were tested for their ability to signal a functional response, induction of major histocompatibility complex class I antigen expression. Replacement of residues 134-209 greatly reduced the ability of the receptor to signal. This signaling defect could not be attributed solely to a reduction in affinity for ligand and could not be localized to any subregion. PMID- 8195199 TI - The effect of Met-->Leu mutations on calmodulin's ability to activate cyclic nucleotide phosphodiesterase. AB - Calmodulin (CaM) has two hydrophobic surface patches that are particularly rich in Met residues, and these are the major contact areas where CaM interacts with its target enzymes. The amino acid Leu has been introduced by site-directed mutagenesis to replace all the Met residues in CaM. All nine individual Met-->Leu mutants of CaM as well as some double and quadruple mutants were expressed in Escherichia coli. All mutants could be purified by calcium-dependent hydrophobic affinity chromatography, indicating that they still expose their hydrophobic surfaces upon binding calcium. Each single Met-->Leu mutation in the C-terminal domain of the protein had little effect on its ability to activate phosphodiesterase (PDE), while a quadruple mutant with four C-terminal Leu residues instead of Met has a significantly lower affinity for PDE. The M36L mutant is a poor activator compared with the other three N-terminal single Met- >Leu mutants, which have a slightly lower affinity for PDE than wild-type CaM. The introduction of a positively charged Arg for Met-145 resulted in an almost complete loss of CaM's ability to activate PDE. Nuclear magnetic resonance spectroscopy was used to show that most CaM mutants retain their overall three dimensional structure. Thus, the altered activation properties appear to arise from differences in the flexibility and polarizability of the Met and Leu sidechains, rather than from structural perturbations. PMID- 8195200 TI - Identification of basic residues involved in substrate binding and catalysis by pyrophosphate-dependent phosphofructokinase from Propionibacterium freudenreichii. AB - Despite overall low identity of sequence between ATP- and PPi-dependent phosphofructo-1-kinases (PFK), an alignment permits the tentative identification of catalytically important residues in PPi-dependent PFK. Seven basic residues of the PPi-dependent PFK of Propionibacterium freudenreichii, Arg-310, Lys-315, Arg 326, Arg-186, Arg-78, Arg-90, and Lys-148 were chosen on the basis of this alignment for site-directed mutagenesis to neutral residues. Mutants R186A, K315A, and R326A had substantial increases of 43-, 389- and 678-fold, respectively, in Km for fructose 6-phosphate relative to wild-type enzyme and relatively small effects on kcat. The modest kinetic effects of mutations at Arg 78, Arg-90, and Arg-310 were not considered to indicate important roles for these residues. On the other hand, mutant K148M had a Km for PPi that was increased by 132-fold and kcat lowered by a factor of 490. Cho and Cook (Cho, Y.-K., and Cook, P.F. (1988) Biochemistry 28, 4155-4160) concluded on the basis of kinetic and chemical modification data that the enzyme utilizes a proton shuttle mechanism and that two lysines are involved in substrate binding. The present data along with our previous data on mutant D151A support a double proton shuttle mechanism involving Asp-151 and Lys-148 with Lys-148, Arg-326, Lys-315, and perhaps Arg-186 being important for substrate binding. PMID- 8195201 TI - Interaction of N-terminal fragments of fibronectin with synthetic and recombinant D motifs from its binding protein on Staphylococcus aureus studied using fluorescence anisotropy. AB - The N-terminal 29-kDa fragment of fibronectin (Fn29K) contains five type I "finger" modules. It binds to heparin, fibrin, and bacteria and is involved in fibronectin (Fn) matrix assembly. Binding to Staphylococcus aureus involves a cell wall-associated protein that contains approximately three repeats of a 38 residue D motif (Signas, C., Raucci, G., Jonsson, K., Lindgren, P.-E., Anantharamaiah, G.M., Hook, M., and Lindberg, M. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 699-703). Synthetic peptides representing D1, D2, and D3, when labeled with fluorescein isothiocyanate (FITC), exhibited increases in fluorescence anisotropy upon addition of Fn29K but not other Fn fragments. The response could be reversed by titration with unlabeled peptides to yield inhibition constants that agreed with the dissociation constants obtained by fitting the initial response. Values of Kd ranged between 2 and 12 microM, with D3 having the highest affinity. Specificity of D3 for Fn29K was further illustrated by the fact that its C-terminal half (D3b, Lys801 to Lys821), when immobilized, selectively adsorbed Fn29K from a thermolysin digest of fibronectin. The binding site in Fn was further localized within Fn29K by analyzing smaller proteolytic or recombinant subfragments. Those containing fingers, F3-5 and F4-5, were purified on D3b-Sepharose and bound FITC-D3b with Kd values of 4-6 microM. Subfragments containing pairs of fingers 1-2, 2-3, or single fingers 1, 4, or 5 were inactive. Whole D1-3, expressed in Escherichia coli and labeled with fluorescein, bound 1.9 mol/mol of Fn29K with Kd = 1.5 nM. F4-5 and F2-3 bound with respective Kd values of 0.35 and 4.4 microM. These and other results indicate that binding of the individual D region peptides is mediated through their C-terminal halves, primarily to fingers 4 and 5 of fibronectin. The possible basis of the much higher affinity of D1-3 is discussed. PMID- 8195202 TI - A second high affinity HU binding site in the phage Mu transpososome. AB - The bacteriophage Mu in vitro transposition reaction proceeds through several higher order nucleoprotein intermediates (transpososomes). One of the requirements for complex assembly is the Escherichia coli sequence-independent DNA-binding protein, HU. This protein has an affinity for Mu transpososomes, which is at least 100 times greater than for supercoiled DNA (Lavoie and Chaconas, 1990). We have recently identified one such high affinity binding site at the Mu left end by converting HU into a chemical nuclease (Lavoie and Chaconas, 1993). Using immunoelectron microscopy, we now report high affinity HU binding to a region(s) distinct from the previously characterized left end site. HU can be removed from this region by a 0.5 M NaCl wash and subsequently reassembled into the complex with high efficiency. Furthermore, chemical modification of the Mu A protein in the Type 1 complex does not block HU reassembly into the transpososome; the high affinity HU binding observed is therefore unlikely to result from A-HU interactions. These findings are corroborated by the ability of eukaryotic HMG-1 to functionally replace HU in transpososome formation and to efficiently assemble into HU-depleted complexes. We propose that HU recognition of an altered DNA structure, rather than protein protein interactions, mediates high affinity HU binding to Mu transpososomes. PMID- 8195203 TI - Biochemical mechanism of HIV-I Vpr function. Specific interaction with a cellular protein. AB - vpr is an accessory gene of human immunodeficiency virus I (HIV-I). Although unnecessary for viral replication in T cell lines, growing evidence suggests that it is essential for virus replication in monocytes/macrophages and for replication in vivo. We expressed HIV-I vpr in Escherichia coli and purified Vpr by affinity chromatography. In a coprecipitation assay, the purified Vpr interacted specifically with a cellular protein designated as Vpr-interacting protein, or RIP. Mutational analysis suggested that this interaction required a domain rich in leucine/isoleucine residues and highly conserved between HIV-I and SIVmac Vprs. During transient expression in mammalian cells, HIV-I Vpr was localized in the nucleus. However, mutational analysis failed to identify in Vpr a typical nuclear localization signal rich in basic amino acid residues. Instead, Vpr nuclear localization seemed to correlate with Vpr interaction with RIP. Mutations in the C-terminal 20-amino acid region containing a cryptic nuclear localization signal did not abolish Vpr nuclear localization or interaction with RIP, whereas point mutations in the leucine/isoleucine-rich domain abolished Vpr interaction with RIP and rendered Vpr unstable during transient expression. These results suggest that RIP may be involved in Vpr function. PMID- 8195204 TI - Isolation of recombinant ADP-ribosylation factor 6, an approximately 20-kDa guanine nucleotide-binding protein, in an activated GTP-bound state. AB - ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide binding proteins, which, like other members of the ras superfamily, are activated by exchanging bound GDP for GTP and inactivated through hydrolysis of the gamma phosphate of bound GTP to form GDP in a highly regulated cycle. ARF 6, a class III ARF, was expressed in Escherichia coli with its amino terminus fused to maltose-binding protein. Following release from maltose-binding protein, recombinant ARF 6 (rARF 6) exhibited maximal activity with or without GTP. Such constitutive activation was due to the predominance of ARF-GTP over ARF-GDP, as demonstrated by nucleotide analysis. rARF 6 expressed in E. coli without amino terminal extension was bound primarily to GDP and exhibited typical GTP-dependent activity. After release from maltose-binding protein, rARF 6-GTP was stable; only a fraction of the nucleotide was removed using EDTA, whereas urea denaturation restored complete GTP dependence. [alpha-32P]GTP bound to rARF 6 was in part protected from hydrolysis by alkaline phosphatase and resulted in the formation of [alpha-32P]GTP, -GDP, and -GMP, whereas unbound nucleotide was completely hydrolyzed to guanosine. Thus, amino-terminal extension of rARF 6, by maltose binding protein, promoted the formation of a constitutively activated GTP-bound species. By analysis of this species, we confirmed that rARF 6 lacks the intrinsic ability to hydrolyze bound GTP and speculate that maltose-binding protein may inhibit hydrolysis by extrinsic factors. PMID- 8195205 TI - Dependence of the folding and import of the precursor to mitochondrial aspartate aminotransferase on the nature of the cell-free translation system. AB - The precursor to mitochondrial aspartate amino-transferase (pmAspAT), when newly synthesized in vitro using either rabbit reticulocyte lysate (RRL) or wheat germ extract (WGE), is highly susceptible to proteolysis. Treatment of these translation products with trypsin generates a characteristic pattern of proteolytic fragments which differs between WGE and RRL. pmAspAT synthesized in RRL acquires over time the trypsin resistance characteristic of purified recombinant pmAspAT in a process that reflects folding of the nascent protein in a cytosolic-like environment and results in the loss of its ability to be imported into mitochondria (Mattingly, J.R., Jr., Youssef, J., Iriarte, A., and Martinez-Carrion, M. (1993) J. Biol. Chem. 268, 3925-3937). Folding in RRL is temperature-dependent. By contrast, pmAspAT synthesized in WGE does not acquire trypsin resistance at any temperature and is unable to be imported into isolated mitochondria. Yet, addition of RRL to the protein synthesized in WGE restores both the folding and import processes. This effect is temperature and N ethylmaleimide-sensitive and requires ATP. We have also detected that newly synthesized pmAspAT, in both the mammalian (RRL) and plant (WGE) environments, associates at an early stage, possibly cotranslationally, with cytosolic hsp70. This complex is transient and short-lived in RRL but is stable for protein synthesized in WGE. The mature form of the protein is also found associated with hsp70 early on during its synthesis. Yet, in RRL, it dissociates from the complex more easily than its precursor form. This suggests that the interaction between the precursor and hsp70 is at least partially dependent on the signal peptide. The dissociation of the precursor/hsp70 complex seems to precede ATP-requiring subsequent folding steps. Furthermore, release of precursor from this complex, either to be imported into mitochondria or to resume folding when in the absence of mitochondria, appears to be influenced by other factor(s) present in RRL but absent or inhibited in WGE. PMID- 8195206 TI - Rotation and membrane topology of genetically expressed methylcholanthrene inducible cytochrome P-450IA1 lacking the N-terminal hydrophobic segment in yeast microsomes. AB - A modified rat liver cytochrome P-450IA1, lacking amino acids 2-30, a proposed membrane anchor for cytochrome P-450, was expressed genetically in yeast microsomal membranes. This truncated cytochrome is practically active in the deethylation of 7-ethoxycoumarin. A full-length cytochrome P-450IA1 was also expressed in yeast microsomes. Rotational diffusion of P-450IA1 was examined by observing the flash-induced absorption anisotropy r(t) of the P-450.CO complex. The anisotropy decayed to a time-independent value within a 2-ms time range. Since the decay curve has the characteristics of a slow rotation of membrane embedded cytochrome, the theoretical analysis of r(t) was performed based on a "rotation-about-membrane normal" model. 41% of the shortened P-450IA1 was rotating with the rotational relaxation time phi of 1020 microseconds, whereas 27% of the full-length P-450IA1 was mobile with phi = 1101 microseconds. The high salt treatment did not remove the shortened cytochrome from the membrane and also did not drastically weaken the interactions of the cytochrome with the membrane, as judged from the slow rotation characteristics (phi = 830 microseconds). These results demonstrate that the N-terminal shortened P-450IA1 is incorporated properly into the yeast microsomal membrane and that the N-terminal hydrophobic segment is not solely responsible for attachment to the membrane, providing evidence that additional segments of P-450IA1 are involved in the membrane binding. PMID- 8195207 TI - A novel member of the immunoglobulin gene superfamily expressed in rat carcinoma cell lines. AB - Defined by monoclonal antibody E4, the pE4 antigen is a 66,000-Da glycoprotein which is expressed at the cell surface of rat colon and mammary carcinomas, but only in trace amounts in normal adult rat tissues. To determine the structure of this tumor-associated antigen and to identify its functional domains, we have cloned a cDNA coding for this protein. It encodes a 416-amino acid protein with an expected molecular weight for the core protein of approximately 42,000. The predicted amino acid sequence reveals that pE4 contains the conserved amino acids and domain structures characteristic of members of the immunoglobulin gene superfamily. Comparison of this sequence with data banks revealed a significant homology with the human and mouse receptors for polio-virus. However, pE4 is not the rat receptor for poliovirus, as different patterns were obtained by hybridization of rat genomic DNA with both probes. A major approximately 2.2 kilobase transcript of the pE4 gene was detected in all the rat tumor cell lines tested. In contrast, barely detectable levels of pE4 mRNA were found in normal adult rat tissues. PMID- 8195208 TI - The complete structure of human class IV alcohol dehydrogenase (retinol dehydrogenase) determined from the ADH7 gene. AB - A novel human alcohol dehydrogenase (ADH) gene called ADH7 has been characterized and determined to encode class IV ADH, an ADH isozyme which is very active as a retinol dehydrogenase. A nearly full-length cDNA for ADH7 was isolated from a human stomach cDNA library, and a 5' genomic clone containing exons 1 and 2 was isolated from a human genomic library. DNA sequence analysis of the cDNA and genomic clones revealed the complete coding region of the gene and the deduced full-length amino acid sequence of human class IV ADH composed of 373 amino acids following the initiator methionine. The class IV identity of the sequence was confirmed by agreement with previously determined sequences for several human stomach class IV ADH peptides. Alignment of the full-length predicted amino acid sequence of human class IV ADH with the full-length sequences of the other four known human ADH classes revealed sequence identities of 69% (class I), 59% (class II), 61% (class III), and 60% (class V). The higher sequence identity shared with human class I ADH suggests that the genes for ADH classes I and IV may have diverged from a common ancestor after the separation of the other classes, and may still share common physiological functions. Discussed is the possibility that one of these functions is retinol oxidation for the synthesis of retinoic acid, a hormone important for cellular differentiation. PMID- 8195209 TI - Effect of high osmolality on Na+/H+ exchange in renal proximal tubule cells. AB - Na+/H+ exchanger isoform and the effect of high osmolality on its function was studied in cultured renal epithelial cells (LLC-PK1 and OK). Using NHE-3-specific antibody, immunoblots of luminal membranes from LLC-PK1 and OK cells specifically labeled proteins with molecular masses 90 and 95 kDa, indicating that NHE-3 is the isoform expressed on the luminal membranes of these epithelia. Proximal tubular suspensions from rabbit kidney cortex were incubated in control (310 mosm/liter) or high osmolality (510 mosm/liter) medium for 45 min and utilized for brush border membrane vesicle preparation. Influx of amiloride-sensitive 22Na+ at 10 s (pHo 7.5, pHi 6.0) into brush border membrane vesicles was 37% lower in the high osmolality group (p < 0.03). LLC-PK1 or OK cells were grown to confluence and examined for Na+/H+ exchange activity. An increase in medium osmolality to 510 mosm following acid loading decreased the 5-min uptake of the amiloride-sensitive 22Na+ in LLC-PK1 and OK cells (p < 0.04 and < 0.03 for LLC PK1 cell OK cells, respectively). An increase in medium osmolality to 510 mosm in vascular smooth muscle cells, which express NHE-1, produced 45 and 64% stimulation of the amiloride-sensitive 22Na+ influx at base-line pHi and acid loaded condition, respectively (p < 0.03 and < 0.01). Down-regulation of protein kinase C by preincubation with phorbol 12-myristate 13-acetate or inhibition of Ca(2+)-calmodulin-dependent protein kinase (calmodulin-kinase II) by N-6 aminohexyl-5-chloro-1-naphthalenesulfonamide (W-7) in LLC-PK1 cells did not block the inhibitory effect of high osmolality on Na+/H+ exchange activity. We conclude that renal proximal tubule epithelial cells express Na+/H+ exchange isoform NHE-3 on their luminal membranes and that hyperosmolality decreases transporter activity during cell acidification. This inhibitory effect might be unique to the NHE-3 isoform, since vascular smooth muscle cells which express NHE-1 exhibit an increase in Na+/H+ exchange activity in response to high osmolality. PMID- 8195210 TI - Arachidonyl trifluoromethyl ketone, a potent inhibitor of 85-kDa phospholipase A2, blocks production of arachidonate and 12-hydroxyeicosatetraenoic acid by calcium ionophore-challenged platelets. AB - Arachidonyl trifluoromethyl ketone (AACOCF3) is a potent and selective slow binding inhibitor of the 85-kDa cytosolic phospholipase A2 (cPLA2) (Street, I. P., Lin, H.-K., Laliberte, F., Ghomashchi, F., Wang, Z., Perrier, H., Tremblay, N. M., Huang, Z., Weech, P. K., and Gelb, M. H. (1993) Biochemistry 32, 5935 5940). AACOCF3 and a number of its structural analogues have been used to investigate the role of cPLA2 in the cellular generation of free arachidonic acid (AA) and in eicosanoid biosynthesis. AACOCF3 inhibited the release of AA from calcium ionophore-challenged U937 cells (IC50 = 8 microM, 2 x 10(6) cells ml-1) and from platelets (IC50 = 2 microM, 4 x 10(7) cells ml-1). Arachidonyl methyl ketone (AACOCH3) and AACH(OH)CF3, both of which are noninhibitory to the purified cPLA2, did not inhibit the production of AA in the ionophore-challenged cells. In addition to the release of AA, AACOCF3 also inhibited the production of 12 hydroxyeicosatetraenoic acid (12-HETE) and thromboxane B2, two of the major metabolites of AA produced by platelets. The inhibition of 12-HETE biosynthesis showed a dose dependence similar to that of AA release in ionophore-challenged platelets; however, when platelet 12-HETE production was stimulated with 10 microM AA to circumvent the PLA2-dependent step, AACOCF3 no longer inhibited the production of 12-HETE. In contrast, AACOCF3 blocked thromboxane B2 formation by both calcium ionophore- and AA-challenged platelets, indicating that the compound affects the cyclooxygenase pathway in addition to AA release. The crude cytosol and membrane fractions from platelets were assayed for calcium-dependent and calcium-independent PLA2 activities and for the susceptibility of each to inhibition by AACOCF3. At AACOCF3 concentrations as high as 10 mol %, only one of the observed PLA2 activities was inhibited by more than 25%. The AACOCF3 susceptible PLA2 (77% inhibition at 1.6 mol %) was found in the cytosolic platelet fraction and showed the functional characteristics of the cPLA2. These results suggest that the cPLA2 plays an important role in the generation of free AA for 12-HETE biosynthesis in platelets. PMID- 8195211 TI - Tight binding inhibitors of 85-kDa phospholipase A2 but not 14-kDa phospholipase A2 inhibit release of free arachidonate in thrombin-stimulated human platelets. AB - An analogue of arachidonic acid in which the COOH group is replaced by a trifluoromethyl ketone group (COCF3) has recently been shown to be a tight binding inhibitor of the 85-kDa cytosolic phospholipase A2 that is found in platelets and other cells (Street, I. P., Lin, H.-K., Laliberte, F., Ghomashchi, F. G., Wang, Z., Perrier, H., Tremblay, N. M., Huang, Z., Weech, P. K., and Gelb, M. H. (1993) Biochemistry 32, 5935-5940). This trifluoromethyl ketone inhibits most of the arachidonate release from the phospholipid pool in thrombin stimulated human platelets at concentrations of 0-40 microM with 4 x 10(8) platelets/ml. A structure-function analysis of related compounds reveals a good correlation between the inhibition of the purified phospholipase A2 and the blockage of arachidonate release in platelets. A number of recently described potent inhibitors of the 14-kDa phospholipase A2 that is secreted from activated platelets have no effect on the level of free arachidonate production. Furthermore, the addition of a large amount of recombinant 14-kDa phospholipase A2 to platelets does not produce free arachidonate, and it does not alter the amount of arachidonate released following platelet activation with thrombin. These studies provide strong pharmacological evidence for the role of the cytosolic phospholipase A2 in producing most, if not all, of the liberated arachidonate in thrombin-stimulated human platelets, and they show that tight binding membrane-residing inhibitors of the cytosolic phospholipase A2 can block the eicosanoid cascade in living cells. PMID- 8195212 TI - Refined structure for the complex of acarbose with glucoamylase from Aspergillus awamori var. X100 to 2.4-A resolution. AB - The three-dimensional structure of the pseudotetrasaccharide acarbose complexed with glucoamylase II(471) from Aspergillus awamori var. X100 has been determined to 2.4-A resolution. The model includes residues corresponding to 1-471 of glucoamylase I from Aspergillus niger, a single molecule of bound acarbose, and 535 sites for water molecules. The crystallographic R factor from refinement is 0.124, and the root-mean-squared deviation in bond distances is 0.013 A. Electron density for a single molecule of bound acarbose defines what may be the first four subsites in the binding of extended maltooligosaccharides. Hydrogen bonds between acarbose and the enzyme involve Arg54, Asp55, Arg305, carbonyl177, main chain amide121, Glu179, Glu180, and carbonyl179. Glu179 forms a salt link to the imino linkage between the first and second residues of acarbose. This buried salt link probably contributes significantly to the unusually tight association (Kd approximately 10(-12) M) of acarbose with glucoamylase. In addition, a significant hydrophobic contact between the third residue of acarbose and the side chain of Trp120 distorts the three-center angle of the glucosidic linkage between the second and third residues of acarbose. A water molecule (water500) hydrogen bonds to Glu400 and the 6-hydroxyl of the valienamine moiety of acarbose and is at an approximate distance of 3.7 A from the "anomeric" carbon of the inhibitor. The relevance of the acarbose-glucoamylase complex to the mechanism of enzymic hydrolysis of oligosaccharides is discussed. PMID- 8195214 TI - A phospholipase A2 inhibitor from the plasma of the South American rattlesnake (Crotalus durissus terrificus). Protein structure, genomic structure, and mechanism of action. AB - The lethal toxicity of the South American rattlesnake (Crotalus durissus terrificus) venom can be attributed mainly to the presence of a pre-synaptic neurotoxin, crotoxin, with phospholipase A2 activity. Crotoxin is a heterodimer of an acidic protein (CA) and a basic phospholipase A2 (CB). An anti-toxic protein of subunit molecular mass 23.6 kDa that neutralizes both lethal and PLA2 activity of crotalid venom and crotoxin has been previously purified from the plasma of this snake (Fortes-Dias, C., Fonseca, B. C. B., Kochva, E., and Diniz, C. R. (1991) Toxicon 29, 997-1008). The protein has been named CNF for Crotalus neutralizing factor. In the present study, we have shown that CNF exists as an oligomeric aggregate of (CNF)n, where n = 6-8, and when it interacts with crotoxin, it replaces the acidic protein CA of crotoxin to form a stable near stoichiometric complex of CNF.CB. The CNF.CB complex no longer exhibits PLA2 activity and is inert in vivo. Thus, the exchange reaction between CA.CB of crotoxin and CNF to form CNF.CB and free CA is reminiscent of the interaction of crotoxin with its target receptor at the neuromuscular transmission site in the presynaptic cells. A cDNA encoding CNF has been isolated from a liver cDNA library using an appropriate nucleotide probe. The nucleotide sequence codes for a 19-residue signal peptide, followed by a 181-residue protein of which 16 are half-cystines. Calculated molecular mass is 20.06 kDa, and there is a putative N linked carbohydrate site at Asn157. PMID- 8195213 TI - Differential role of the carboxyl-terminal tyrosine in down-regulation and sequestration of the m2 muscarinic acetylcholine receptor. AB - Muscarinic acetylcholine receptor (mAChR) number can be altered in response to sustained agonist exposure. Short term agonist exposure (seconds to minutes) causes a rapid removal of mAChR from the cell surface (sequestration) while agonist exposure for longer periods of time (hours) causes a decrease in total receptor number (down-regulation). Tyrosine residues located in the cytoplasmic tails of a number of membrane receptors have been demonstrated to be important in the regulation by either sequestration, as is the case with the mannose 6 phosphate receptor and other receptors endocytosed via clathrin coated vesicles, or down-regulation, as is the case with the beta 2-adrenergic receptor. Mutation of the lone cytoplasmic tail tyrosine residue (Tyr-459) of the mammalian m2 mAChR to Phe, Trp, or Ala did not affect agonist-induced sequestration, although it significantly attenuated agonist-induced down-regulation. Conversion of m2 Tyr 459 to Ile did not affect the rate or extent of agonist-induced sequestration or down-regulation, but the sensitivity of this mutant receptor to agonist-induced down-regulation was slightly decreased. Agonist and antagonist binding as well as functional coupling to the inhibition of cAMP accumulation was unaffected by any of the mutations to Tyr-459. These results are the first to identify a site in a mAChR involved in the down-regulation of receptor in response to agonist. PMID- 8195215 TI - An intricate arrangement of binding sites for the Ets family of transcription factors regulates activity of the alpha 4 integrin gene promoter. AB - alpha 4 integrins mediate cell-cell and cell-extracellular matrix interactions that are critical for maturation and function of the immune system as well as differentiation of skeletal muscle. Here we examine molecular mechanisms controlling the pattern of alpha 4 expression. The activity of constructs containing 5' deletion mutants of the alpha 4 gene promoter was compared in transfection assays into cell lines that express alpha 4 and cell lines that do not. The sequence between position -42 and -76 base pairs (bp) was required for efficient transcription in cells that express alpha 4, but it showed no activity in HeLa cells, which do not express alpha 4. Three binding sites for the Ets family of transcription factors are found in this region: two adjacent sites at positions -50 and -54 bp and a more 5' site at position -67 bp. Using a series of constructs containing deletions and mutations in this region, we found that the 3'-most site alone was sufficient for binding GA-binding protein alpha (GABP alpha)/GABP beta and for a low level of transcriptional activation. When all three sites were present, a second complex "a" was detected, which contains an unknown member of the Ets family. Formation of complex a was cell-type specific and correlated with a high level of transcription. Deletion of the 5'-most Ets site had no effect on binding to GABP alpha/GABP beta, but it eliminated a. Concomitant with this loss of a, a new Ets-1-containing complex "c" appeared. Complex c substituted efficiently for complex a in transcriptional activation. We conclude that although neither of the two 5'-most Ets sites alone binds nuclear protein, they appear to act as modulators which control the pattern of Ets proteins that bind the alpha 4 gene promoter. This arrangement of Ets sites, coupled with the tissue- and developmental-specific expression of Ets members, likely play a key role in defining the pattern of alpha 4 integrin. PMID- 8195217 TI - Molecular cloning, expression, and characterization of PTPA, a protein that activates the tyrosyl phosphatase activity of protein phosphatase 2A. AB - PTPA, or phosphotyrosyl phosphatase activator, is a protein that stimulates the tyrosyl phosphatase activity of protein phosphatase 2A in an ATP, Mg(2+) requiring reaction (Cayla, X., Goris, J., Hermann, J., Hendrix, P., Ozon, R., and Merevede, W. (1990) Biochemistry 29, 658-667). We constructed oligonucleotide probes based on the amino acid sequences of peptides isolated from purified PTPA and used them to probe rabbit muscle and human heart cDNA libraries. A putative full-length clone was isolated from the rabbit skeletal muscle as well as from the human heart library. The nucleotide sequence of both clones contains an open reading frame of 969 nucleotides starting from an assigned initial ATG codon and encodes for a protein of 323 amino acids. The predicted rabbit and human PTPA protein sequences show an identity of 96.6%. The predicted protein matched all the peptide sequences obtained from the rabbit skeletal muscle protein. Bacterially expressed protein, as well as the in vitro reticulocyte lysate translation product, comigrated with the purified 37-kDa protein on sodium dodecyl sulfate-polyacrylamide gels. Both proteins reacted with immunopurified, anti-PTPA polyclonal antiserum. The recombinant protein was a soluble and active protein. Northern blot analysis revealed two transcripts of 2.8 and 4 kilobases, respectively, in human placenta but only one 2.8-kilobase transcript in rabbit and rat tissues. High levels of PTPA mRNA were detected in testis, which contrasted with the low levels present in skeletal muscle. PMID- 8195216 TI - GCN4p activation of the yeast TRP3 gene is enhanced by ABF1p and uses a suboptimal TATA element. AB - Transcription of the TRP3 gene of Saccharomyces cerevisiae is regulated by GCN4p from a position proximal to the transcriptional initiation sites. The promoter's apparent lack of a conventional TATA element sequence has led it to be used as a model for TATA-less promoters. Through mutational analysis of the TRP3 promoter, we have identified two additional regulatory elements required for expression. The first, located 57 base pairs (bp) upstream of the GCN4p binding site, binds ABF1p in vitro. The ABF1p binding site was required for maximal levels of GCN4p activated transcription in vivo; however, the -fold activation by GCN4p was not altered by ABF1p. The second element, positioned 23 bp downstream of the GCN4p binding site, contained the TATA-like sequence, TATTAA. This element was required for both basal and activated expression and almost certainly functions as a TATA binding protein interaction site. Mutations that improved its TATA character for native or an altered specificity mutant of TATA-binding protein correspondingly improved its function. Interestingly, basal expression induced by ABF1p was virtually unchanged in the presence of point mutations in the TATTAA element. Furthermore, unlike the case for HIS3 where only a limited subset of TATA-like sequences can activate transcription in conjunction with GCN4p, many divergent TATA-like sequences allowed GCN4p activation of TRP3. We suggest that the apparent promoter specific use of these TATA elements by GCN4p results from ABF1p amplifying the GCN4p-induced expression to a detectable level. PMID- 8195218 TI - Rapid internalization of the polymeric immunoglobulin receptor requires phosphorylated serine 726. AB - S726 of the cytoplasmic domain of the polymeric immunoglobulin receptor (pIgR) resides within a consensus sequence for phosphorylation by protein kinases A, G, and C, and casein kinase II. Mutation of S726 to Ala and expression of this mutant pIgR in Madin-Darby canine kidney cells results in a receptor in which steady-state phosphorylation is reduced to 49% of wild-type levels. This mutant receptor is also significantly impaired in its internalization from the basolateral membrane. During the first minute, internalization of radioiodinated ligands (either dIgA or monovalent anti-pIgR Fabs) by this mutant pIgR is only 35% of that by wild-type pIgR. Internalization of unoccupied mutant receptors is similarly inhibited. Delivery of newly made mutant receptor from the trans-Golgi network to the basolateral surface is completely normal. The only other trafficking step inhibited by this mutation is the transcytosis of radioiodinated dIgA. Within 2 h, the mutant pIgR will transcytose 58% of a preinternalized cohort of dIgA, while the wild-type transcytoses 76%. This inhibition of transcytosis may be an indirect consequence of impaired internalization. The correlation between the loss of phosphorylation and inhibition of internalization suggests that phosphorylation of S726 may represent a novel mechanism for regulation of internalization of the pIgR. PMID- 8195219 TI - Cloning of two novel ADP-ribosylation factor-like proteins and characterization of their differential expression in 3T3-L1 cells. AB - A polymerase chain reaction-based cloning approach was employed in order to identify ADP-ribosylation factors (ARF) in murine 3T3-L1 cells and to study their expression before and after differentiation of cells to the adipocyte-like phenotype. Partial sequences comprising the effector domains of ARF were amplified with degenerate primers and cloned. Five of these sequences were identified as murine homologues of known human ADP-ribosylation factors (ARF 1, 2, 4, 5, and 6). In addition, partial sequences of two previously unknown isoforms were found, and complete cDNA clones were isolated from a rat fat cell library and were sequenced. Both sequences harbor a putative myristoylation site in position 2, the known consensus sequences presumably involved in GTP binding and hydrolysis, and lack cysteine residues in the C terminus. Their amino acid sequences share a 56 and 41% identity, respectively, with human ARF 1. Based on a comparison with the known ARF isoforms, the first clone appears to represent the mammalian homologue of a known sequence from Drosophila (dARL 1, 79% identity) and was therefore designated rARL 1. The second clone resembled none of the known ARF-like proteins and was designated rARL 4. mRNA of ARL 4 was undetectable in the fibroblasts but abundant in the adipocyte-like phenotype, its expression starting on day 6 of the differentiation. In contrast, ARF 1, 2, and 5 were unaltered by differentiation of the 3T3-L1 cells; mRNA levels of ARF 6, and also of ARL 1 and ARF 4, were reduced after differentiation. It is suggested that the function of ARL 4 is related to the adipocyte-like phenotype of 3T3-L1 cells. PMID- 8195220 TI - Ribosomal protein P0, contrary to phosphoproteins P1 and P2, is required for ribosome activity and Saccharomyces cerevisiae viability. AB - Protein P0 in Saccharomyces cerevisiae is found only in the ribosomes and not free in a cytoplasmic pool like the structurally related acidic P1 and P2 proteins. Analogously, P0 stays bound to the particles in conditions that release the other P proteins. Attempts to obtain yeast strains carrying an interrupted P0 gene by direct gene disruption techniques of different yeast strains always resulted in haploid cells carrying one disrupted and one intact copy of the gene. Disruption of the unique P0 genomic copy seems to induce a duplication and occasionally a chromosomal transposition of the gene. Conditional null mutants of P0 were then constructed carrying the P0 gene under the control of the inducible GAL1 promoter. A 2-3-fold excess of P0 mRNA is found in the conditional mutant when grown in galactose; however, only a small increase of the P0 protein is detected in total cell extracts. No P0 protein is detected in the cell supernatant, indicating that, like the standard ribosomal proteins and opposite to the other P proteins, the protein not bound to the ribosomes is degraded. Transfer of the mutants to the restrictive conditions causes, after some generations, a growth stop that finally leads to cell death. The growth decline is paralleled by a reduction in the polysome number and the appearance of half mer particles as well as by an accumulation of 60 S particles deficient in P0 and in the acidic proteins P1 and P2. These results indicate that P0 is required for the interaction of the acidic P1 and P2 proteins with the ribosomes, and in its absence, deficient 60 S ribosomes are assembled which are inactive in protein synthesis resulting in cell lethality. PMID- 8195221 TI - Purification and characterization of a novel organometallic receptor protein regulating the expression of the broad spectrum mercury-resistant operon of plasmid pDU1358. AB - The narrow spectrum mercury-resistant (mer) operons of transposons Tn21 and Tn501 are inducible by inorganic mercury salts. The major regulatory gene merR is transcribed divergently from the other mer genes, which are cotranscribed. The MerR protein represses its own expression, as well as the expression of the other mer genes in the absence of the inducers. The synthesis of the polycistronic mer message is stimulated by MerR in the presence of the inducers. The MerRBS protein encoded by the broad spectrum mer operon of plasmid pDU1358 was characterized as a novel organomercurial receptor, distinguishing it from the narrow spectrum MerRNS proteins, described above. Several organomercurial compounds directly effected cellular activation of the mer operon transcription via the receptor protein MerRBS, but not by MerRNS. The merR gene from pDU1358 was cloned under the tac promoter, and the overexpressed MerRBS protein was soluble in buffer solutions containing 0.5 M NaCl at pH 7.5, but precipitated when NaCl concentration was reduced to 0.1 M (MerRBS concentrations at or above 0.1 mg/ml). MerRBS was purified to near homogeneity by selective precipitation and solubilization by varying the salt concentration in buffer solutions, followed by Sephadex G-75 column chromatography. Both MerRBS and Tn21-encoded MerRNS bound with DNA fragments containing the pDU1358 mer operator sequence with comparable affinities. In vitro run-off transcription studies revealed that MerRBS activated mer operon expression in the presence of Hg2+ or phenylmercuric acetate. Phenylmercuric acetate did not induce mer operon expression when the MerRNS was used in the assay. PMID- 8195222 TI - Na-K-2Cl cotransport in intestinal epithelial cells. Influence of chloride efflux and F-actin on regulation of cotransporter activity and bumetanide binding. AB - Although cAMP-dependent epithelial chloride secretion is largely regulated via apical membrane chloride channels, cAMP also remodels basolateral F-actin and activates basolateral Na-K-2Cl cotransport. Whether activation of cotransport is a primary event or secondary to activation of chloride efflux is not established, and the basis for the cytoskeletal dependence is unknown. We studied cotransport in the intestinal line HT29 (which lacks cAMP-regulated chloride efflux) and in its subclone Cl.19A (in which this pathway is present). Cotransporter activity was enhanced by forskolin in both lines but to a considerably greater extent in subclone Cl.19A, in which the number of bumetanide binding sites was also observed to increase. The F-actin stabilizer phalloidin markedly attenuated cAMP stimulated cotransport in Cl.19A monolayers, but the increase in bumetanide binding was preserved. These studies identify two mechanisms for activation of Na K-2Cl cotransport by cAMP: components independent and dependent of cAMP-elicited chloride efflux. Additional Na-K-2Cl cotransporters become accessible to the cell surface coincident with the salt efflux-dependent activation of cotransport. While F-actin rearrangements influence salt efflux-dependent up-regulation of the cotransporter, this influence occurs independently of increases in bumetanide accessible cotransporters. PMID- 8195223 TI - Characterization of denatured protein inducers of the heat shock (stress) response in Xenopus laevis oocytes. AB - In addition to thermal stress, a large variety of physical and chemical treatments are known to induce heat shock gene expression. Denatured protein, thought to result from the stress condition, has been postulated to act as the common signal. Accordingly, of three pairs of native and denatured proteins injected into Xenopus laevis oocytes, only the denatured derivatives induced expression of a reporter gene from a heat shock promoter (Ananthan, J., Goldberg, A. L., and Voellmy, R. (1986) Science 232, 522-525). These observations are extended here. Protein denaturation per se is shown to be insufficient for heat shock induction; although reduced and carboxymethylated bovine serum albumin (rcm BSA) and alpha-crystallin elicited a stress response, many other denatured proteins had no effect. Methylation of protein lysines, done to prevent ubiquitination, suppressed heat shock induction by rcm-BSA, but enhanced induction by alpha-crystallin. Thus, the potential for a protein to be ubiquitinated is independent of its ability to induce the stress response. Instead, aggregation distinguished the proteins that were effective stress inducers, and the formation of large aggregates correlated with the magnitude of the response. This correlation may derive in part from decreased in vivo degradation rates of the inducer proteins. An apparent requirement for stress response induction that the inducer proteins be injected directly into the oocyte nucleus may relate to this issue of in vivo stability. The dependence of the stress response on the amount of injected protein is non-linear and of a form consistent with the titration of a factor that otherwise suppresses heat shock gene expression. PMID- 8195224 TI - hsc70 moderates the heat shock (stress) response in Xenopus laevis oocytes and binds to denatured protein inducers. AB - Injections of hsc70 protein into Xenopus oocytes lowered the stress response to both a thermal shock and to co-injected protein inducers. Binding of hsc70 to native and modified forms of bovine serum albumin (BSA) were tested by two assays. In one, nitrocellulose-bound proteins were incubated with hsc70, cross linked with glutaraldehyde, and then bound hsc70 was probed with a monoclonal anti-hsc70 antibody. In the second, peroxidase-conjugated hsc70 was employed as a more direct probe for binding to proteins displayed on nitrocellulose membranes. hsc70 binding to the BSA derivatives correlated with their abilities to induce a stress response upon microinjection into oocytes. Reduced and carboxymethylated (rcm) BSA, the most potent stress inducer tested, was bound most tightly by hsc70, whereas hsc70 had moderate affinity for N-methylated rcm-BSA and very little affinity for the native protein. No binding was observed with iodinated BSA. The results suggest a mechanism whereby the cell employs hsc70 or other proteins of the hsp70 family both to trigger the response to an environmental stress and to provide a feedback mechanism to attenuate the response. PMID- 8195225 TI - Quantitative analyses of electrostatic interactions between NADPH-cytochrome P450 reductase and cytochrome P450 enzymes. AB - A decline in the ionic interactions in the medium with increasing ionic strength (decrease in the ionic activity coefficients) was accompanied by an increase in the fast phase rate constants of CYP2B4 and CYP1A2 reduction. The stimulations were observed both in reconstituted P450 systems and in microsomes. An increase in the ionic strength from 10 to 100 mM sodium phosphate resulted in a 7-fold decrease in the Km of CYP1A2 for NADPH-cytochrome P450 reductase, while the Vmax was unchanged. When ionic interactions were neutralized without changing the ionic strength by addition of charged oligopeptides (polylysine and polyglutamic acid), stimulations of CYP1A2 and CYP2B4 reduction were observed. Increase in the ionic strength also enhanced the rate of cytochrome P450 reduction in control and phenobarbital-induced rat liver microsomes and in reconstituted systems containing purified rat liver CYP2C6, CYP2C12, CYP2C13, and CYP2E1, and rat reductase. A method was devised for the quantification of the number of charges involved in protein-protein interactions based on the estimation of the ionic activity coefficients. Different numbers of charged residues are involved in the repulsion between different P450 forms and the reductase. The product of the number of charges involved in the interaction between rabbit reductase and CYP2B4 is 10.84 compared with the value of 6.64 for the reductase-CYP1A2 interaction. PMID- 8195226 TI - The basolateral targeting signal in the cytoplasmic domain of glycoprotein G from vesicular stomatitis virus resembles a variety of intracellular targeting motifs related by primary sequence but having diverse targeting activities. AB - Using systematic site-directed mutagenesis, the basolateral targeting signal in the cytoplasmic domain of glycoprotein G from vesicular stomatitis virus (VSV G) has been localized to an 11-amino acid sequence, which contains two essential residues and a third that makes a minor contribution. A tyrosine at position 19 of the 29-residue carboxyl-terminal cytoplasmic tail is the most important residue and cannot be replaced by other aromatic amino acids, while an isoleucine at position 22, 3 residues carboxyl-terminal to this tyrosine, is also critical but can be replaced by other aliphatic residues. Additionally, an arginine at position 16 makes a minor contribution. Therefore the crucial elements of this targeting signal can be represented by the sequence Y-X-X-aliphatic. While earlier investigation has suggested similarity between basolateral targeting and internalization signals, alignment of this sequence with other cytoplasmic targeting signals suggests the existence of a broad class of homologous targeting motifs that direct protein delivery to a variety of cellular locations. This in turn suggests the existence of a family of homologous receptors, distributed throughout the cell, which differ in their affinity for subsets of these targeting sequences. PMID- 8195227 TI - Mutagenic alteration of the distal switch II region of RAS blocks CDC25-dependent signaling functions. AB - We have explored the role of the distal switch II region of the yeast RAS2 protein in determining the response to the nucleotide exchange factor CDC25. We first constructed yeast tester strains in which the deletion of the chromosomal CDC25, RAS1, and RAS2 genes, in combination with the chromosomal suppressor CRI4, resulted in detectable phenotypes in vivo and in vitro. Phenotypes included impaired growth at 37 degrees C, defective glucose-induced cyclic AMP signaling, and low adenylyl cyclase activity of membrane preparations. Tester strains were subsequently used for the reintroduction of various combinations of wild-type and mutated RAS2 and CDC25 genes by genetic techniques, as well as for in vitro reconstitution assays with the corresponding proteins. CDC25 restored both growth and glucose-induced cyclic AMP signaling in the presence, but not in the absence of wild-type RAS2. A gene encoding a RAS2 protein with a mutationally altered switch II region was expressed but was ineffective in reintegrating exchange factor-dependent responses in vivo. Wild-type, but not mutagenically altered, RAS2 proteins were stimulated by exchange factors in vitro. We conclude that the conserved distal switch II region is required for CDC25-dependent activation of RAS. PMID- 8195228 TI - Postendocytic trafficking of epidermal growth factor-receptor complexes is mediated through saturable and specific endosomal interactions. AB - Intracellular trafficking of the epidermal growth factor receptor (EGF-R) is regulated by receptor occupancy. To investigate this, we developed an assay to study endosomal sorting under steady-state conditions. Using a cell line transfected with EGF-R variants, we found that the fraction of internalized EGF.EGF-R complexes sorted to lysosomes was a function of the number of intracellular complexes and required sequences in the cytoplasmic domain of the receptor. As the number of intracellular occupied wild-type receptors increased from 3 x 10(2) to 2 x 10(5)/cell, the fraction of internalized EGF that was degraded dropped from 70 to 20%. Transforming growth factor-alpha, which dissociates from the EGF-R at endosomal pH, was degraded to a uniform extent of approximately 50% at all intracellular ligand concentrations. EGF internalized by receptors lacking a cytoplasmic domain (c'647) was degraded to an extent of only 5-10% independent of the number of intracellular complexes. Mutant receptors truncated either at residues 1022 or 973 displayed sorting patterns intermediate between wild-type and c'647 receptors. Despite large differences in their internalization rates, the fractional sorting patterns of c'1022 and c'973 receptors were indistinguishable. Receptor tyrosine kinase activity appeared to have a small effect on sorting pattern, but only in the context of full-length receptors. Our results indicate that the default pathway of internalized receptors is rapidly recycling and that lysosomal targeting of occupied EGF-R is due to endosomal retention that is both specific and saturable. In addition, internalization and endosomal retention of EGF-R appear to be mediated by distinct structural elements. PMID- 8195229 TI - Feedback regulation of mitogen-activated protein kinase kinase kinase activity of c-Raf-1 by insulin and phorbol ester stimulation. AB - Recently, it has been reported that Raf-1 kinase (Raf-1) has mitogen-activated protein kinase kinase kinase (MAPKKK) activity in various cells, although Raf-1 and MAP kinase kinase (MAPKK) can be phosphorylated by MAP kinase (MAPK) in vitro. Here we show that the maximal hyperphosphorylation of Raf-1 and MAPKK (10 min) was substantially achieved after the maximal activation of MAPKKK of Raf-1, MAPKK (2-5 min), and MAPK in Chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR cells) treated with insulin or 12-O tetradecanoylphorbol-13-acetate (TPA). Moreover, we show that overexpression of MAPK in CHO-HIR cells resulted in enhanced hyperphosphorylation of Raf-1, MAPKK, and mammalian homolog of son of sevenless (mSos) after insulin or TPA stimulation as compared with parental cells. Furthermore, the maximal hyperphosphorylation of Raf-1 appears to be accompanied by a significant decrease in MAPKKK activity. These results suggest that 1) signals initiated by insulin and TPA converge on Raf-1 and activate its MAPKKK activity and 2) Raf-1, MAPKK, and mSos not only lie upstream of MAPK but also are phosphorylated by MAPK, directly or indirectly, and at least Raf-1 kinase activity might be down-regulated by this feedback mechanism. PMID- 8195230 TI - Transcription of the rat alpha 1B adrenergic receptor gene in liver is controlled by three promoters. AB - The proximal 5'-flanking region of the rat alpha 1B adrenergic receptor (alpha 1BAR) gene contains discrete transcription start points (tsp) utilized in liver, located at -54, -57 (tsp1), and -443 base pairs (tsp2) upstream from the translation start codon (Gao, B., and Kunos, G. (1993) Gene (Amst.) 131, 243 247). Primer extension analyses using 5' upstream primers now identify an additional cluster of tsp between -1035 and -1340 base pairs (tsp3). Northern blots of rat liver mRNA reveal three alpha 1BAR mRNAs of 2.3, 2.7, and 3.3 kilobases in length. Transient transfections of putative promoter/pCAT constructs document the existence of three promoters, P1 (-127, -49), P2- (-813, -432), and P3 (-1363, -1107), which direct transcription from tsp1, tsp2, and tsp3, respectively. P1 contains no recognition sequences for known transcription factors. P2 is (G + C)-rich, lacks a TATA box, and contains a cAMP response element, GC, CACC, and GCAAT boxes, and binding sites for nuclear factor I. P3 contains a putative TATATA and CCAAT box and is flanked by recognition sites for the liver-specific CCAAT/enhancer binding protein and hepatocyte nuclear factor 5. These findings indicate that heterogeneity of alpha 1BAR mRNA in liver is related to transcription of the gene by three distinct promoters. Differential control of these promoters may underlie the well documented developmental and tissue-specific regulation of the alpha 1BAR. PMID- 8195231 TI - c-Myb-induced trans-activation mediated by heat shock elements without sequence specific DNA binding of c-Myb. AB - The c-myb proto-oncogene product (c-Myb) can transactivate the human hsp70 promoter in a transient cotransfection assay. The present studies have demonstrated that the heat shock element (HSE) in the hsp70 promoter mediates trans-activation by c-Myb. Mutagenesis of the DNA sequence in HSE indicated that the NGAAN motif is necessary for not only the heat shock response but also the c Myb-induced trans-activation. The HSE in the hsp70 promoter does not contain a c Myb-binding site, implying that the sequence-specific DNA binding of c-Myb is not required for the HSE-dependent trans-activation by c-Myb. We had demonstrated that a disruption of the leucine zipper motif in the central portion of the c-Myb molecule increased the degree of c-Myb-induced trans-activation of the promoter containing c-Myb-binding sites, suggesting that a putative inhibitor binds to c Myb through this leucine zipper (Kanie-Ishii, C., MacMillan, E. M., Nomura, T., Sarai, A., Ramsay, R. G., Aimoto, S., Ishii, S., and Gonda, T. J. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 3088-3092). However, disruption of the leucine zipper in c-Myb abolished the HSE-dependent trans-activation by c-Myb, whereas deletion of the transcriptional activation domain containing acidic amino acids in c-Myb did not abolish the HSE-dependent trans-activation by c-Myb. These results suggest that c-HSEs by interacting with unidentified trans-acting factor(s) but not by a direct binding to the promoter through its DNA-binding domain. PMID- 8195232 TI - Inhibition of G protein-coupled receptor signaling by expression of cytoplasmic domains of the receptor. AB - The third intracellular domain (3i) of G protein-coupled receptors plays a major role in the activation of G proteins. Alterations in this region of the receptor can affect receptor/G protein coupling efficiency and specificity. We recently reported (Luttrell, L. M., Cotecchia, S., Ostrowski, J., Kendall, H., Lefkowitz, R.J. (1993) Science 259, 1453-1457) that coexpression of the 3i domain of the alpha 1B adrenergic receptor (AR) (alpha 1B3i) specifically inhibited alpha 1BAR mediated inositol phosphate production, with no effect on D1A dopamine receptor (D1ADR)-mediated cAMP production. Similarly, expression of the 3i domain of D1ADR (D1A3i) inhibited D1ADR-mediated cAMP production but did not affect alpha 1BAR mediated inositol phosphate accumulation. This suggests that peptides derived from a G protein-coupled receptor might serve as antagonists of receptor/G protein interactions. The present studies were performed to test the generality as well as the specificity of this phenomenon. The effect of expression of the second intracellular domain (2i), the 3i domain, and the fourth intracellular domain (4i) of alpha 1BAR on second messenger generation mediated by the alpha 1BAR, the M1 muscarinic cholinergic receptor (M1AChR), and the D1ADR was examined. Although the alpha 1B2i domain had no effect on receptor/G protein coupling for any receptor tested, the alpha 1B3i domain inhibited signaling mediated by alpha 1BAR and M1AChR but not by D1ADR, while the alpha 1B4i domain inhibited signaling mediated by each of the receptors. To investigate the generality of 3i domain-induced inhibition of receptor activity further, the 3i domains of two Gq-coupled receptors (alpha 1BAR and M1AChR) and two Gi-coupled receptors (alpha 2AAR and M2AChR) were tested for effects on the second messenger generation mediated by each of the four receptors. In each case, the homologous 3i domain caused significant inhibition (40-60%), while the 3i domain of the receptor coupled to the same G protein also decreased receptor/G protein coupling. In contrast, receptor/G protein coupling appeared unaffected by expression of 3i domains derived from receptors coupled to different G proteins. The alpha 1B3i domain-provoked inhibition of homologous receptor signaling was surmountable at high receptor density, and assays using a phorbol response element/reporter gene construct detected a weak enhancement of basal second messenger generation in cells expressing the alpha 1B3i domain alone.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8195233 TI - Molecular cloning and expression of alternatively spliced PITSLRE protein kinase isoforms. AB - Minimal ectopic expression of the p58GTA protein kinase results in a provocative phenotype involving cell cycle delay, mitotic catastrophe, and decreased cell viability. In addition, this kinase is well conserved evolutionarily, ubiquitously expressed, and its genes map to a position on human chromosome 1 frequently deleted in the late stages of tumorigenesis. Here we report that the p58GTA protein kinase is a member of a larger subfamily of proteins. The mRNAs encoding these proteins are generated by alternative splicing from multiple duplicated genes. These isoforms range in size from 50 to 110 kDa. Divergence between the alternatively spliced isoforms is localized to the amino-terminal region of the molecule. The entire p58GTA open reading frame is conserved in most of these p58GTA isoforms. The predicted sequences of the larger isoforms encode bipartite nuclear localization signal sequences and extensive polyglutamic acid domains. Antibodies to the p58GTA isoform were used to confirm the presence of the alternatively spliced isoforms in different cell types as well as identify two additional isoforms that appear to arise from a separate gene(s). Cellular fractionation studies indicate that one of the isoforms is found only in the nucleus, and the remainder are found in both the cytoplasm and the nucleus. Expression and localization of some p58GTA isoforms suggest that they may have specialized cellular functions. Because of the large number of isoforms generated from multiple genes we propose naming these kinases PITSLRE alpha 1, alpha 2-1, alpha 2-2, alpha 2-3 alpha 2-4, beta 1, beta 2-1, and beta 2-2 based on the conserved sequence of the PSTAIRE box unique to p34cdc2 kinases and the gene from which they are transcribed. PMID- 8195234 TI - High level expression in Escherichia coli and characterization of the EF-hand calcium-binding protein caltractin. AB - Caltractin is a member of the calmodulin superfamily of Ca(2+)-binding proteins that was originally cloned at the DNA level from the unicellular green alga Chlamydomonas reinhardtii. Human and mouse homologs to algal caltractin have been recently characterized. In the studies reported here, recombinant Chlamydomonas caltractin was expressed at high levels in Escherichia coli and purified to homogeneity. The use of the ompT-host BL21 proved critical for obtaining high yields of homogeneous full-length protein. Growth and purification protocols were optimized to allow reproducible and efficient production of tens of milligrams of pure protein from 1-liter cultures. Caltractin has a distinct UV spectrum which is largely dominated by the fine structure due to the 9 Phe residues. Unlike other members of the same protein family, the UV and the CD spectra do not change upon addition of Ca2+ to the apoprotein. However, the 1H NMR spectrum shows distinct changes upon Ca2+ binding, which are indicative of structural and/or dynamic changes largely reminiscent of other members of the calmodulin superfamily. Ca2+ binding measurements demonstrated the binding of four Ca2+ ions to caltractin with two higher affinity (Kd = 1.2 x 10(-6) M) and two lower affinity (Kd = 1.6 x 10(-4) M) sites. Caltractin is highly stable in both the apo and the Ca(2+)-loaded states. The unusual stability of apocaltractin makes this protein highly suited for structural studies by multidimensional NMR aimed at understanding the structural and dynamic consequences of Ca2+ binding, and the molecular basis of Ca2+ signal transduction. PMID- 8195235 TI - Myosin I from mammalian smooth muscle is regulated by caldesmon-calmodulin. AB - A single-headed monomeric myosin (myosin I) was isolated from pig urinary bladder smooth muscles and purified to homogeneity. Myosin I from smooth muscle is composed of a 110-kDa heavy chain and three 17-kDa light chains. The heavy chain from smooth muscle myosin I does not cross-react with the antibody against conventional myosin (myosin II) from smooth muscle, but it does show antigenic similarity to adrenal medulla myosin I heavy chain. The light chain from smooth muscle myosin I is similar to calmodulin in molecular weight, amino acid composition, and migration on SDS-polyacrylamide gel electrophoresis in the presence of Ca2+. The high salt ATPase activity of myosin I in the presence of CaCl2 is higher than that in K(+)-EDTA. Smooth muscle actin causes a 5-10-fold activation of the Mg-ATPase activity of myosin I. In the presence of Ca2+, exogenous calmodulin enhances the actin-activated ATPase activity of myosin I, and the increased activity is associated with the binding of exogenous calmodulin to myosin I heavy chain. A maximum of 4 mol of light chains/mol of myosin I heavy chain is observed in the presence of exogenous calmodulin. Caldesmon, a calmodulin/actin-binding protein, inhibits the actin-activated ATPase activity of myosin I. This inhibition is reversed by exogenous calmodulin in the presence of Ca2+. The actin activation of myosin I ATPase exhibits around 50% Ca2+ sensitivity in the presence of exogenous calmodulin. When caldesmon is bound to actin, Ca2+ sensitivity is increased to 80% in the presence of calmodulin. Therefore, smooth muscle caldesmon, which is thought to play a role in the regulation of actin activation of myosin II, also regulates the actin activation of myosin I ATPase in smooth muscle. PMID- 8195236 TI - Recombinant pulmonary surfactant protein D. Post-translational modification and molecular assembly. AB - Pulmonary surfactant protein D (SP-D) is a member of a family of collagenous C type lectins that includes the serum mannose binding proteins and surfactant protein A. Recent studies have shown that rat SP-D (rSP-D) molecules are assembled as tetramers of trimeric subunits (12 mers) and that dodecamers can participate in higher orders of molecular assembly involving interactions of the amino-terminal peptide domains. In order to further study the assembly of SP-D in vitro, Chinese hamster ovary K1 cells were transfected with a full-length rat SP D cDNA, and stable transfectants with high levels of SP-D production (approximately 6 x 10(6) dodecamers/cell/24 h) were obtained using a glutamine synthetase selection system. The secreted molecules (RrSP-D), which were purified by affinity chromatography on maltosyl-agarose, comigrated with rSP-D on SDS polyacrylamide gel electrophoresis in the presence and absence of reduction, and coeluted with rSP-D dodecamers from 4% agarose. The major bacterial collagenase resistant peptide showed a decreased mobility on reduction consistent with the formation of intrachain disulfide bonds. A 17-kDa pepsin-resistant fragment was isolated following overnight digestion with pepsin at 27 degrees C, confirming the formation of a triple helical domain comparable in size and thermal stability to that of natural SP-D. The expressed protein contained sialylated endoglycosidase F-sensitive carbohydrate; amino acid analysis of acid and alkaline hydrolysates demonstrated essentially normal levels of hydroxyproline, hydroxylysine, and hydroxylysine-glycosides. Electron microscopic studies showed a molecular structure indistinguishable from lung SP-D, with a similar small subpopulation of molecules showing higher orders of multimerization. Solid-phase neoglycoprotein binding assays gave the same saccharide inhibition profile as natural rat SP-D, and both proteins showed efficient saccharide-dependent agglutination of Escherichia coli. These studies demonstrate that a single genetically distinct chain type can account for the various and complex molecular assemblies of SP-D, and further verify the potential physiologic significance of the disulfide-bonded multimers and higher aggregates isolated from rat, bovine, and human lung lavage. PMID- 8195237 TI - Insulin synthesis, secretory competence, and glucose utilization are sensitized by transgenic yeast hexokinase. AB - Glucokinase regulates insulin secretion by controlling the rate of glucose phosphorylation. In this report we utilize islets transgenic for high affinity yeast hexokinase to examine the role of glucose phosphorylation on other beta cell functions. Normal pancreatic islets responded to culture in low glucose by lowering insulin synthetic rates, becoming depleted of insulin and insulin mRNA, losing competence to respond to glucose with increased insulin secretion, and lowering glucokinase levels by one-half. In transgenic islets, increased high affinity hexokinase activity provided significant protection against reductions in all parameters of insulin synthesis and helped preserve the competence of beta cells to secrete insulin. The transgenic hexokinase also increased the rate of glucose utilization. These results demonstrate that glucose phosphorylation and presumably glucokinase mediate these glucose regulated responses. Of the parameters measured, only the change in glucokinase activity did not show an effect of the yeast hexokinase transgene. We also found that yeast hexokinase transgene expression was regulated 10-fold by glucose. This is the first demonstration of glucose inducibility of the insulin promoter in transgenic mice. PMID- 8195238 TI - Molecular cloning of a chiral-specific 3 alpha-hydroxysteroid sulfotransferase. AB - A novel stereoselective hydroxysteroid sulfotransferase (HST) that acts on neutral steroids having the 3-hydroxyl group in the alpha orientation but not on steroids where the 3-hydroxyl group is oriented in the beta position has been cloned and expressed. Primary screening of a guinea pig adrenal cDNA library was performed by colony hybridization using an oligonucleotide probe based on a highly homologous region among known steroid sulfotransferases. Selected clones consisted of overlapping sequences but were incomplete. The rapid amplification of cDNA ends procedure was used to construct a full-length guinea pig HST cDNA. The guinea pig HST cDNA transiently transfected into Chinese hamster ovary K1 cells expressed a protein identical in size to that of purified guinea pig HST specific for 3 alpha-hydroxylated neutral steroids that was recently reported (Driscoll, W. J., Martin, B. M., Chen, H.-C., and Strott, C. A. (1993) J. Biol. Chem. 268, 23496-23503). The expressed HST likewise exhibited sulfotransferase activity that was directed specifically toward steroid substrates containing a 3 hydroxyl group in the alpha orientation; on the other hand, steroids with a 3 beta-hydroxyl group were not sulfonated by the expressed HST. Thus, the cloned HST cDNA clearly coded for a steroid sulfotransferase with chiral specificity for 3 alpha-hydroxylated neutral steroids and was, therefore, given the designation of guinea pig 3 alpha-hydroxysteroid sulfotransferase (gp3 alpha-HST). The full length gp3 alpha-HST cDNA consisted of 1182 base pairs and coded for a protein containing 287 amino acids. The deduced amino acid sequence of the protein shares 65/79, 65/80, and 62/76% identity/similarity with rat, mouse, and human HST, respectively. Northern blot analysis of guinea pig tissues revealed no apparent gender differences in either mRNA species or distribution; a single 1.4-kilobase HST mRNA species was present in adrenal and liver tissue. Interestingly, the adrenal mRNA content was considerably more abundant than that found in the liver. Evidence for 3 alpha-HST mRNA was not detected in kidney, heart, lung, muscle, spleen, or uterus. PMID- 8195240 TI - A novel O-tigloyltransferase for alkaloid biosynthesis in plants. Purification, characterization, and distribution in Lupinus plants. AB - A novel acyltransferase for alkaloid metabolism, tigloyl-CoA: (-)-13 alpha hydroxymultiflorine/(+)-13 alpha-hydroxylupanine O-tigloyltransferase (HMT/HLTase), a monomeric 50-kDa protein, was purified to homogeneity from 10-day old Lupinus termis seedlings. There were two isoforms of this acyltransferase with the same molecular mass (50 kDa) but slightly different isoelectric points (pI 7.8 and 7.6). These two isoforms showed the same catalytic activity of tigloyl transfer from tigloyl-CoA to (-)-13 alpha-hydroxymultiflorine and (+)-13 alpha-hydroxylupanine, which belong to the same (7S, 9S) enantiomeric series of tetracyclic quinolizidine alkaloids; whereas no activity was detected toward an antipodal (7R, 9R) alkaloid, (-)-baptifoline, or to bicyclic quinolizidine alkaloids, (+)-epilupinine and (-)-lupinine. The Km values for HMTase activity were determined to be 21 microM and 46 microM for (-)-13 alpha hydroxymultiflorine and tigloyl-CoA, respectively; and for HLTase activity, 27 microM and 52 microM for (+)-13 alpha-hydroxylupanine and tigloyl-CoA, respectively. The activity was inhibited by CoASH in a competitive manner, and by (+)-lupanine and (+)-epilupinine in a partially noncompetitive manner. The enzyme showed the highest activity around pH 8.0 and was inactivated by heat treatment and by the addition of sulfhydryl blocking reagents. Such tigloyltransferases for quinolizidine alkaloid metabolism are distributed in some Lupinus species and Cytisus scoparius, in which tigloyl alkaloids are accumulated in addition to non ester-type alkaloids, but not in other lupin plants, in which only non-ester-type alkaloids are present. PMID- 8195239 TI - Thrombin-mediated phosphoinositide hydrolysis in Chinese hamster ovary cells overexpressing phospholipase C-delta 1. AB - The regulatory mechanism(s) of a phosphoinositide-specific phospholipase C, PLC delta 1, was investigated using a clone of stably overexpressed PLC-delta 1 (PLC delta 30 cells) in Chinese hamster ovary cells. Thrombin stimulation of PLC delta 30 cells exhibited 6.5-fold increase in total inositol phosphates (InsP), which was significantly higher than that in the vector-transfected (V1) cells (2.0 fold). AIF-4 increased InsP accumulation in both V1 and PLC delta 30 cells, and pertussis toxin partially blocked InsP accumulation in thrombin-stimulated PLC delta 30 cells. Guanosine thiotriphosphate (GTP gamma S) markedly potentiated thrombin-stimulated InsP generation in permeabilized PLC delta 30 cells compared with V1 cells, suggesting possible involvement of a G-protein (s) in the activation of PLC-delta 1. In PLC delta 30 cells, ionomycin-induced significant InsP generation and thrombin-stimulated InsP generation were completely inhibited by addition of EGTA. Furthermore, the stimulatory effects of thrombin plus GTP gamma S in PLC delta 30 cells were more sensitive to change in free calcium concentration than in V1 cells. Suppression by 12-O-tetradecanoylphorbol 13 acetate of thrombin-stimulated InsP accumulation was not affected by increasing Ca2+ concentration. These results indicate that thrombin-induced PLC-delta 1 activation is regulated via both G-protein(s) and calcium. PMID- 8195241 TI - Identification of a tripartite basal promoter which regulates human terminal deoxynucleotidyl transferase gene expression. AB - In order to locate the promoter region of the human terminal deoxynucleotidyl transferase gene, serially truncated segments of the 5'-flanking region of the gene were cloned into a chloramphenicol acetyltransferase reporter vector. Transient transfection analyses of the terminal transferase-reporter gene constructs identified the basal promoter region within -34 to +40 base pairs relative to the transcription start site. Three promoter elements were defined in this region. The primary element is within 34 base pairs upstream of the transcription start site. The CAP site is 62 base pairs upstream of the translation start site. The secondary element involves sequences around the transcription start site. The third is located 25 base pairs downstream from the initiation site (+25 to +40). This tripartite basal promoter was not tissue specific; similar patterns of promoter activity were observed in terminal transferase expressing and non-expressing cells. Transfection analyses also indicated the presence of negative regulatory elements upstream of the basal promoter region, and these elements were preferentially active in cells expressing terminal transferase. PMID- 8195242 TI - Transcriptional protein binding domains governing basal expression of the rat luteinizing hormone receptor gene. AB - The functional importance of specific protein binding domains on transcription within the GC-rich 173-base pair promoter of the luteinizing hormone receptor gene was studied by mutagenesis and gel retardation analysis. Transcription was dependent on the presence of two Sp1 elements in the promoter domain of transfected expressing mouse Leydig tumor cells (mLTC) and nonexpressing Chinese hamster ovary cells. Mutation of two protein binding domains located downstream of the Sp1 elements (M1 and C-box) revealed tissue-specific regulation of promoter activity by each domain. Also, gel retardation studies indicated the presence of multiple trans factors that bind to the C-box and M1 domains. Removal of the AP-2 element from the C-box resulted in mLTC-specific transcriptional activation that may involve an M1/C-box interaction. In addition, competition by overlapping NF-1 and AP-2 elements was demonstrable in both the C-box and upstream R domain for separate trans factors that exhibit neutral or inhibitory functions, respectively. Competition between the inhibitory and neutral DNA binding factors within both upstream and promoter domains may be responsible for a mechanism that controls the on/off state of luteinizing hormone receptor gene expression in gonadal cells. These studies reveal a complex pattern of transcriptional regulation that may reflect targeted mechanisms for the control of luteinizing hormone receptor gene expression. PMID- 8195243 TI - Localization of the high and low affinity [3H]ryanodine binding sites on the skeletal muscle Ca2+ release channel. AB - The Ca2+ release channel of skeletal muscle sarcoplasmic reticulum is modulated in a biphasic manner by the plant alkaloid ryanodine and there are two distinct binding sites on this channel for ryanodine. The Ca2+ release channel is a homotetramer with a subunit of 5037 amino acids. The ability of sarcoplasmic reticulum membranes to bind [3H]ryanodine to the high affinity site is lost upon proteolysis with trypsin. [3H]Ryanodine, however, bound before proteolysis remains bound after trypsin digestion. If the high affinity site is first occupied with [3H]ryanodine and then 100 microM ryanodine is added to occupy the low affinity sites, almost all of [3H]ryanodine bound to the high affinity site remains bound after proteolysis. Proteolysis causes the solubilized Ca2+ release channel containing bound [3H]ryanodine to undergo four discrete shifts in sedimentation (30 S-->28 S-->26 S-->19 S-->14 S). Polypeptides having apparent molecular masses of 76, 66, 56, 45, 37, and 27 kDa can be identified in the 14 S complex. The 76-, 56-, 45-, and 27-kDa polypeptides have been partially sequenced from the NH2 terminus. In addition, the 76-, 66-, and 27-kDa fragments are recognized by an antibody to the last 9 amino acids at the carboxyl terminus of the skeletal muscle ryanodine receptor and the 76-, 66-, and 37-kDa fragments are recognized by an antibody to a peptide matching the sequence 4670-4685. The 56 kDa and the 45-kDa fragments are not Ca2+ release channel fragments. Both high and low affinity ryanodine binding sites are found in the 14 S complex and are, therefore, most likely located between Arg-4475 and the carboxyl terminus. PMID- 8195244 TI - In vitro and in vivo studies of antagonistic effects of human growth hormone analogs. AB - A bovine growth hormone (bGH) analog, bGH-G119R, has been shown to act as a functional antagonist of GH activity both in vitro and in vivo. In the present study, human (h) GH analogs with alterations in the third alpha-helix (G120A, G120R) and N terminus (I4A) were generated. These two regions have been reported to form binding site 2 in hGH, which is involved in in vitro dimerization of the GH receptor (GHR). The biological activities of these hGH analogs were tested in vitro by a radioreceptor assay and an assay to test the ability of the molecules to induce tyrosine phosphorylation of a 93-kDa protein in a human lymphocyte line, IM-9. The growth rate of transgenic mice that express different hGH analogs was used as an in vivo test of the activity of the molecules. The results demonstrated that G120R is a potent hGH antagonist both in vitro and in vivo. Transgenic mice expressing G120R demonstrated a growth-suppressed phenotype. However, I4A, which has been demonstrated to be a potent inhibitor of in vitro GHR dimerization, exhibited full growth promoting activity in transgenic mice. Thus, the ability of hGH analogs to induce GHR dimerization in vitro and the ability to promote growth in vivo are not directly correlated. PMID- 8195245 TI - Insensitivity of the present hsp26 chromatin structure to a TATA box mutation in Drosophila. AB - The role of the TATA element in establishing the chromatin structure and inducible transcription of the Drosophila melanogaster hsp26 gene has been analyzed. An hsp26/lacZ fusion gene with a mutant promoter, in which the TATA box sequence TATAAA was changed to CCCAAA, was introduced into Drosophila by P element transformation. The mutation had little effect on formation of the preset chromatin structure observed prior to induction. However, the mutation dramatically reduced transcription levels following heat shock. Northern analysis indicated that weak, inducible expression of the mutant promoter occurred within the same period of heat shock as for the normal promoter, suggesting that TFIID was associated with the mutant promoter prior to heat shock. Biochemical analysis showed that the mutant promoter still bound TFIID in vitro, but with 3-5-fold less affinity than the normal promoter. DNase I footprinting revealed that the conformation of the TFIID-DNA complex differed significantly from that of the normal promoter. These results indicate that alterations in the conformation or the stability of the TFIID-DNA complex drastically reduce the level of induction, but do not dramatically affect chromatin structure formation. Formation of the requisite chromatin structure is either independent of, or highly tolerant of, changes in the TFIID-DNA complex. PMID- 8195246 TI - Estrogen receptor-Sp1 complexes mediate estrogen-induced cathepsin D gene expression in MCF-7 human breast cancer cells. AB - Cathepsin D is an estrogen (17 beta-estradiol, E2)-inducible lysosomal protease. A putative estrogen receptor (ER)-Sp1-like sequence (GGGCGG(n)23ACGGG) has been identified in the non-coding strand of the cathepsin D promoter (-199 to -165), and electromobility shift assays of nuclear extracts from MCF-7 and HeLa cells confirm that both the ER and Sp1 protein bind to 32P-labeled ER/Sp1 oligo. For example, nuclear extracts from MCF-7 cells bind to the 32P-labeled ER/Sp1 oligo; however, ER/Sp1 binding can be decreased by selective competition with excess unlabeled estrogen responsive element and Sp1 oligos, immunodepletion with ER or Sp1 antibodies, and by treating cells with ICI 164,384, an antiestrogen which inhibits formation of ER homodimer. Moreover, E2-induced chloramphenicol acetyltransferase (CAT) activity in MCF-7 cells cotransfected with a human estrogen receptor expression plasmid and a plasmid containing an ER/Sp1 sequence cloned upstream to a thymidine kinase promoter and a CAT reporter. In cotreatment studies, ICI 164,384 inhibited E2-induced CAT activity. In contrast, E2 did not induce CAT activity in MCF-7 cells transfected with plasmids containing mutations in the ER or Sp1 segments of the ER/Sp1 oligo, thus confirming that both cognate binding sites are required for estrogen responsiveness. PMID- 8195247 TI - Structure/activity analysis of human monocyte chemoattractant protein-1 (MCP-1) by mutagenesis. Identification of a mutated protein that inhibits MCP-1-mediated monocyte chemotaxis. AB - Monocyte chemoattractant protein-1 (MCP-1) is a monocyte-specific chemoattractant and activator and is a member of the chemokine-beta family of cytokines. To identify regions of MCP-1 which are required for its biological activity, we constructed human MCP-1 mutants that were expressed in eukaryotic cells and tested for their ability to attract monocytes in vitro. Deletion of amino acids 2 8 destroyed activity, suggesting that the amino-terminal region is necessary for activity. Within the deleted region, mutation of aspartate 3 to alanine produced a protein with 9% of wild-type activity, whereas mutation of asparagine 6 to alanine produced a protein with 52.9% of wild-type activity. Mutation of amino acids within the first intercysteine loop yielded variable results. Changing tyrosine 28 to aspartate or arginine 30 to leucine each produced proteins with essentially no monocyte chemoattractant activity. The side chains of these amino acids are predicted to point into a putative receptor binding cleft, and these loss-of-function mutations are consistent with this model. Also consistent is the retention of 60% of wild-type activity after mutation of serine 27 to glutamine, since the side chain of serine 27 is predicted to point away from the binding cleft. However, mutation of arginine 24, which lies outside of this area, to phenylalanine produced a protein with only 5% of wild-type activity, suggesting more complex interactions. Truncations of the carboxyl terminus, as well as mutation of aspartate 68 to leucine, generated proteins with 10-20% of wild-type activity. (Another carboxyl-terminal insertional mutation demonstrated that O linked carbohydrate in MCP-1 alpha may be added to a threonine in the carboxyl terminal region.) These findings are consistent with a structural model of dimeric MCP-1 which is similar to interleukin-8, in which amino acids that point into a cleft between the two carboxyl-terminal alpha-helices of the subunits are important for receptor binding. In addition, however, amino acids at the amino terminus and others outside of the interhelical cleft are also essential for activity. The carboxyl-terminal alpha-helix is not required for signaling per se but is required for maximal specific activity. Finally, four mutant proteins partially inhibited the ability of wild-type MCP-1 to attract monocytes in vitro.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8195248 TI - Amino acids Asn796 and Thr799 of the Ca(2+)-ATPase of sarcoplasmic reticulum bind Ca2+ at different sites. AB - The Ca(2+)-binding properties of mutants Asn796-->Ala, Thr799-->Ala, and Glu908- >Ala of the sarcoplasmic reticulum Ca(2+)-ATPase were analyzed in studies of CrATP-induced Ca2+ occlusion and of the Ca2+ dependencies of phosphorylation from ATP and P(i). The Asn796-->Ala and Thr799-->Ala mutants were unable to occlude Ca2+, whereas the Glu908-->Ala mutant was fully capable of occluding Ca2+. Mutant Asn796-->Ala was unable to form a phosphoenzyme from ATP, whereas mutants Thr799- >Ala and Glu908-->Ala phosphorylated from ATP with K0.5 values for Ca2+ activation of 3 and 0.4 mM, respectively. In the Asn796-->Ala mutant, Ca2+ inhibited phosphorylation from P(i) with a K0.5 value of less than 10 microM, whereas in mutants Thr799-->Ala and Glu908-->Ala, the K0.5 values for Ca2+ inhibition of phosphorylation from P(i) were much higher and similar to the K0.5 values observed for Ca2+ activation of phosphorylation from ATP. These data are consistent with a model in which the respective side chains of Asn796 and Thr799 are assigned to two different Ca2+ sites being involved in Ca2+ occlusion, while the side chain of Glu908 is excluded as a direct Ca2+ ligand in the Ca2+ occluded complex. The dephosphorylation of the ADP-insensitive E2P phosphoenzyme intermediate was blocked in the Asn796-->Ala mutant, suggesting the possibility that Asn796 participates in the countertransport of protons. PMID- 8195249 TI - Carboxypeptidase U, a plasma carboxypeptidase with high affinity for plasminogen. AB - A novel basic carboxypeptidase clearly different from carboxypeptidase N has been isolated from human plasma. It circulates as an enzymatically inactive precursor enzyme bound to plasminogen. During fibrinolysis, it can be converted to its active form, carboxypeptidase U, through the action of plasmin. The active enzyme has an apparent molecular weight of 53,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It hydrolyzes the synthetic peptides hippuryl-L-arginine and hippuryl-L-lysine but, in contrast to other human basic carboxypeptidases, has only a limited esterase activity. After its activation, carboxypeptidase U tends to be very unstable. PMID- 8195250 TI - Expression cloning of a GM3-specific alpha-2,8-sialyltransferase (GD3 synthase). AB - A cDNA encoding a GM3-specific alpha-2,8-sialyltransferase (GD3 synthase) was obtained from an expression cDNA library of human melanoma cell line WM266-4 by enrichment of Namalwa KJM-1 cells highly expressing GD3 using an anti-GD3 antibody and a fluorescence-activated cell sorter. Selection of B-cell line Namalwa cells expressing transfected cDNAs in the presence of anti-GD3 monoclonal antibody KM641 gave a cDNA (pAMo-GD3) encoding a protein with a type II transmembrane topology as found for mammalian glycosyltransferases. The following evidence confirms that the cDNA encodes an alpha-2,8-sialyltransferase, which specifically converts GM3 to GD3. (i) Transfection of pAMo-GD3 into Namalwa KJM-1 cells leads to the appearance of GD3 and a GD3 synthase activity. (ii) Northern blot analysis revealed a correlation between the expression of this gene and GD3 in several cell lines. (iii) The putative COOH-terminal active domain of this cloned enzyme fused with protein A has been purified with IgG-Sepharose beads and has been shown to possess GD3-synthesizing activity, excluding the possibility that the cloned cDNA encodes a transacting factor inducing a GD3 synthase. The deduced primary sequence also contains the "sialyl motif" conserved among all the sialyltransferases cloned to date. The polymerase chain reaction analysis reveals that this gene is located on chromosome 12. PMID- 8195251 TI - The effect of wound management on the interaction of burn size, heat production, and rectal temperature. AB - Metabolic and temperature data were collected for 56 patients with burns managed with four wound care protocols. Group I (n = 7) treated with dressings and variable ambient temperature selected for patient subjective comfort; group II (n = 7) managed without dressings and variable ambient temperature for patient comfort; group III (n = 6) no dressings, ambient temperature of 25 degrees C and the output of electromagnetic heaters adjusted for patient comfort; group IV (n = 36) dressings and ambient temperature of 28 degrees C. All groups were cold challenged: groups I and II by sequentially lowering ambient temperature, group III by decreasing the electromagnetic heater output, and group IV by removing dressings with ambient temperature remaining at 28 degrees C. Only groups II and IV demonstrated correlation between percent body surface area burn and heat production. The slope of the regression for group IV neutral was significantly less than that for group IV cold and group II neutral and cold. The relationship between percent body surface area burn and rectal temperature for groups I, II, and III neutral was equal to .03 degrees C increase in rectal temperature per 1% body surface area burn (Y = 37 + 0.03; r = 0.74; df 18; p < 0.01) and was not significantly different when cold. This predicts a 1.5 degrees C increase in rectal temperature for a patient with a 50% body surface area burn who does not have sepsis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195252 TI - Proteolytic activity in burn wound exudates and comparison of fibrin degradation products and protease inhibitors in exudates and sera. AB - Proteolytic (caseinolytic) activity in burn wound exudates was screened over the range pH 5.3 to 8.4. Although activity was greatest at pH 8.4 in four of seven exudates, individual differences indicated that different proteases predominate in the local environment of the wound. Paired exudate and serum samples were compared with regard to fibrin degradation products and three protease inhibitors: antithrombin III, a1-protease inhibitor, and a2-antiplasmin. Fibrin degradation products concentration was higher in exudates than in paired sera, indicating the wound as the source of circulating fibrin degradation products rather than intravascular coagulation followed by fibrinolysis. In contrast, all three protease inhibitors exhibited higher concentrations in serum than in the paired exudate. The serum/exudate ratio for AT III differed significantly from that for a1-protease inhibitor and a2-antiplasmin, and the ratio of two inhibitors in serum differed from the ratio of the same two inhibitors in the exudate in two of three comparisons. These findings emphasize the importance of exudate examinations as a reflection of events in the wound itself. The importance of microenvironments is invoked to account for the significant exudate fibrin degradation products titers, which are seen despite the presence of antithrombin III, which could inhibit coagulation, and the presence of a2 antiplasmin, which could inhibit fibrin degradation. PMID- 8195253 TI - The use of biobrane II and specialty airflow beds (FluidAir Plus and Kinair for effective coverage of extensive posterior donor site wounds. AB - Posterior skin graft donor sites furnish large areas of skin for wound coverage, but the sites frequently are management problems. The wounds tend to become moist and to develop excessive drainage and fluid accumulation that may interfere with adherence of dressings, including our preferred donor site dressing, Biobrane II (red label, large pore). We studied the use of specialty airflow beds for improving the outcome of posterior donor sites. We evaluated 50 patients aged 1 to 69 years (mean 29.45 years) with posterior skin graft donor sites of the back, thigh, or buttocks that were covered with Biobrane II. Sites ranged in size from 3% to 13% body surface area (mean 8.34%). Forty patients were placed on a FluidAir Plus bed, and 10 were placed on air-filled pillow therapy beds (five on KinAir III, five on Therapulse) (Kinetic Concepts, Inc.) All patients were kept in the supine position. We evaluated six criteria: drainage, fluid accumulation under Biobrane, infection, days until Biobrane separated, days until epithelialization, and days of specialty bed usage. We related these criteria to nursing-care actions that interfere with airflow and prevent the drying action of the bed, such as use of a "linen saver" under the patient in the area of the donor site, a foam wedge under the back, and dressings applied over the Biobrane. Most donor sites had no complications. Donor site infections developed in six patients. Five of these patients had fluid accumulation under the Biobrane, necessitating early removal. Fluid accumulated under the Biobrane in 21 patients; nine of these incidences were related to a nursing-care action that impeded airflow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195254 TI - North American survey of hydrotherapy in modern burn care. AB - To investigate the role of hydrotherapy in the treatment of patients with burns, a survey was conducted of the use of hydrotherapy in Canada and the United States as part of an intensive investigation into the causes of Pseudomonas aeruginosa infections in burn injury. Results of the survey conducted indicate that hydrotherapy continues to be an important part of burn wound care in most (94.8%) burn centers in North America. Of the burn centers that use hydrotherapy, 81.4% continue to immerse patients, 82.8% perform hydrotherapy on all patients with burns regardless of total body surface area, and 86.9% continue with hydrotherapy throughout the entire phase of the patient's hospitalization. Routine culturing of the hydrotherapy equipment is standard procedure in 49.7% of the units surveyed, and culturing of the water supply to the equipment on a regular basis is done in only 18.6% of those burn units regularly using hydrotherapy. Pseudomonas aeruginosa was identified as the most common, major cause of sepsis in 52.9% of the burn units surveyed, Staphylococcus aureus in 25.5%, and Candida albicans in 5.2%. This survey demonstrates the extensive use of hydrotherapy in North American burn units and the concern for serious infections in patients with burns from gram-negative organisms such as Pseudomonas species. With the increasing number of reports of Pseudomonas infections related to the use of hydrotherapy equipment, the importance for further investigation into burn wound care with and without hydrotherapy, infection rates, and cost analysis appears to be indicated. PMID- 8195255 TI - Posttraumatic stress disorder in patients with burns. AB - Among 39 patients with burns evaluated a mean of 12 months after hospital discharge, 38% met DSM-III-R criteria for post-traumatic stress disorder (PTSD) for at least 1 month. With proposed DSM-IV criteria, 43% met criteria for past or current PTSD. Analysis of specific symptom clusters of PTSD revealed that 74% of patients had been affected by a reexperience symptom for at least 1 month, but only 30% were currently experiencing flashbacks. No correlation was found between several clinical correlates (TBSA, length of hospitalization, and age) and development of PTSD. There was no correlation between presence of a DSM-III-R psychiatric diagnosis at the time of hospitalization and later development of PTSD and no correlation between whether or not a psychiatric diagnosis emerged during hospitalization and later development of PTSD. Finally, patients who had injuries that they could not prevent were no more likely to experience PTSD. PMID- 8195256 TI - Injury-induced inhibition of fat absorption. AB - Burn injury inhibits lipoprotein lipase, which leads to an impeded clearance of triglycerides from the plasma and an increase in serum triglycerides. Intestinal brush border lipase, which hydrolyzes triglyceride to free fatty acids and is essential for absorption of triglycerides from the gastrointestinal tract, could also be inhibited by burn injury. In thermally injured rats, the absorption and oxidation of enterally administered 14C-palmitate triglyceride, brush border lipase activity, and small-intestinal and colonic content of fat were determined. Absorption of 14C-palmitate triglyceride and production of 14CO2 were reduced 50% 18 hours after injury (p < 0.01). In addition, brush border lipase activity was reduced 50% (p < 0.01). Because brush border lipase function is essential to the proper absorption of enterally administered fat, inhibition of intestinal lipase could be an important factor in enteral diet effectiveness. PMID- 8195257 TI - Posttraumatic stress disorder in mothers of children and adolescents with burns. AB - This is the first study of of posttraumatic stress symptoms in parents (24 mothers and one father) of children with burns. The purpose of the study was to determine what factors relate to parental posttraumatic stress disorder (PTSD). Because the sample is all mothers, except for one father, the conclusions are about mothers. Through use of the Structured Clinical Interview for DSM-III-R, symptoms were determined as occurring from the time of the burn injury until 1 month before the interview (past), 1 month before the interview only (present), or from the date of the burn trauma up to and including 1 month before the interview (past and present). By Structural Clinical Interview criteria, 52% of the mothers had past PTSD, with four (31%) of those mothers having present PTSD symptoms. Eleven mothers and the one father reported neither past nor present PTSD. Multiple regression analysis revealed that larger burns were more strongly related to present PTSD symptoms than were proximity, social support, or perceived stress. Additional findings indicated that mothers with more than one child burned and those mothers who were burned themselves met diagnostic criteria for PTSD. Implications are that posttraumatic stress symptoms can be disruptive to a mother feeling capable of caring for her child with burns after the injury. Individual and group therapy during and after a child's hospitalization may be useful for mothers to reduce stress and to develop better coping skills. PMID- 8195258 TI - Visible scars and self-esteem in pediatric patients with burns. AB - The supposition of often made that visible scarring is more psychologically damaging than are "hidden" burn scars, but little evidence exists to support that idea. We compared the self-evaluations of 28 male and 21 female pediatric patients with burns to the amount and visibility of scars. Males were 6 to 18 years old at the time of burn and sustained 15% to 99% total body surface area burns. They were evaluated 1 to 6 years after their burn injury. Females constituted a similar group. They were 5 to 18 years old at the time of burn, sustained 15% to 94% total body surface area burns, and were evaluated 1 to 7 years after their burn injury. All of the children underwent evaluation with the Piers-Harris Children's Concept Scale, evaluating themselves on intellectual and school status, physical appearance, anxiety, happiness and satisfaction, and behavior and popularity. Scores from these parameters were compared against each child's "visible" scars as seen on the face, head, neck, and hands. Also, comparisons were made with the numbers of reconstructive needs in these areas. Significant inverse correlations were found in the males. As the number of scars increased in these areas, the patient's scores for "physical appearance" and "happiness and satisfaction" decreased (p < 0.001). Other psychologic parameters were not affected. There was no effect by age of patient, and no significant correlations were found for the female group. The results emphasize the importance of the burn team's awareness that pediatric survivors of burns may appear superficially to be adjusting well, while harboring grave self-deprecating feelings. Those with "visible" scars will need special support to enhance self esteem. PMID- 8195259 TI - Vocal cords dysfunction resulting from heterotopic ossification in a patient with burns. AB - Limitation of movement of vocal cords developed in a 38-year-old man after he received a 45% second- and third-degree burn with ossification about the cricoarytenoid joints, which indicated that the lesion had been caused by heterotropic ossification. To the best of our knowledge, this is the first report in medical literature of heterotopic ossification as a mechanical cause of vocal cords dysfunction in the patient with critical burns. Diphosphonate (Didronel) treatment has improved the function of the vocal cords after 11 months of therapy. PMID- 8195260 TI - Estimation of nitrogen requirements in patients with burns. PMID- 8195261 TI - Architectural barriers to persons with disabilities in businesses in an urban community. AB - It is the purpose of this study to determine the frequency of architectural barriers to persons with disabilities in businesses in a small urban community in central Virginia. The survey was conducted by a trained volunteer using a one page checklist. Only 27% of the businesses had no architectural barriers to individuals with disabilities. The most common architectural barrier for individuals with disabilities was the interference with parking and entrance into the business (65%). Faced with these architectural barriers, all individuals are encouraged to identify the architectural barriers in businesses and to file letters of complaints to the Department of Justice requesting their removal. PMID- 8195262 TI - Compliance with pressure garment use in burn rehabilitation. AB - Pressure garment use is recommended 23 to 24 hours a day for hypertrophic scar control after a burn injury. Compliance with this treatment has not been documented. A 52-question survey was administered to 101 adult outpatient burn survivors to rate compliance with this program. The average compliance of each patient was assessed. The framework of the Health Belief Model was used to identify the patients' beliefs and factors reported to interfere with compliance. Strategies patients believed to enhance garment use were identified. Forty-one percent of the patients reported total compliance. The difficulties with garment use such as discomfort and activity limitations appeared to promote low compliance. The primary strategies patients believed would enhance compliance were seeing outcome pictures of scars and having contact with other survivors. This step toward identifying compliance rates and factors that affect them will guide the health care worker in techniques to facilitate adherence to the scar management program. PMID- 8195263 TI - Burn unit survival strategies in changing economic times. PMID- 8195264 TI - Pain assessment from patients with burns and their nurses. AB - We investigated pain experienced during burn wound debridement. Forty-nine adult patients with burns and 27 nurses submitted 123 pairs of visual analog scale pain ratings for burn wound debridements. While patients' overall visual analog scale pain scores were found to be evenly distributed, worst pain scores yielded a bimodal distribution with groups centered around means of 2.0 (low pain group) and 7.0 (high pain group). Low and high pain groups did not differ in age, sex, or total body surface area burned. Patient and nurse pain ratings were found to be highly correlated. According to one researcher's criteria, 53% of nurse pain ratings were accurate. Accuracy of nurses' ratings was unrelated to nursing experience or educational level. Future strategies are presented for comparing high and low pain groups and increasing nurse pain rating accuracy. PMID- 8195265 TI - Enteral feeding during operative procedures in thermal injuries. AB - Multiple surgical procedures necessitated by thermal trauma traditionally require withholding nutritional support during the perioperative period. Significant caloric deficits develop with subsequent catabolism of body tissues to provide energy and amino acids for the synthesis of protein. Eighty patients, matched for age and total body surface area burn, were enrolled in a study to evaluate the safety and efficacy of providing enteral support throughout operative procedures. All patients had duodenal feeding tubes placed under fluoroscopy and were provided with isonitrogenous nutritional support calculated to meet measured energy needs (indirect calorimetry). Forty patients received enteral support throughout 161 surgical procedures, and 40 had enteral support withheld during 129 procedures. Age, incidence of inhalation injury, percentage of total body surface area, and postburn day of admission were similar in both groups. Nutritional parameters, calorie counts, and infectious complications were recorded during the first 4 weeks after burn. No patient in either group experienced aspiration. The unfed group demonstrated a significant caloric deficit (p < 0.006) and increased incidence of wound infection (p < 0.02) and required more albumin supplementation to maintain serum levels at a minimum of 2.5 gm/dl (p < 0.04). Enteral nutrition can be provided safely during the perioperative period and provides the additional benefits of reducing caloric deficits, wound infections, and exogenous albumin supplementation. PMID- 8195266 TI - Patient-centered conference. PMID- 8195267 TI - Pharmacokinetics of morphine sulfate in patients with burns. AB - Morphine sulfate (MS) pharmacokinetics was evaluated in seven patients with a mean body surface area burn of 21.5% to ascertain a rational basis for the management of pain in patients with burns. Treatments included a MS constant rate infusion followed by an oral MS solution (MS-OS) (5 to 15 mg administered every 3 hours) and then a 30 mg MS-controlled release tablet (MS-CR) every 8 hours. Each treatment was separated by a washout period when sampling of morphine was done. The apparent terminal half-life for MS-OS was 3 hours, which is similar to that of patients without burns, but the apparent terminal half-life for the MS-CR in patients with burns was substantially longer at 14.7 hours. The mean time to reach peak concentration for MS-CR was delayed relative to MS-OS 1.4 versus 0.5 hours, and the peak concentration was attenuated. The mean release time of the MS for the CR tablet is about 15 hours. The renal clearances of the MS-CR (114 ml/min) and MS-OS (147 ml/min) were less than the measured creatinine clearance (177 ml/min) but greater than the creatinine clearance (106 ml/min) predicted for a healthy individual. The prolonged release of MS-CR makes the MS-CR a good choice in the management of pain in patients with burns on an 8- to 12-hour dosing schedule, even though the patient might exhibit an increased clearance. PMID- 8195268 TI - Sequential by-passes for limb salvage. AB - Direct revascularisation of the foot permits the healing of distal trophic lesions. This is not always possible with a by-pass on a single isolated popliteal segment. When multi-segmental occlusive arterial lesions were found in femoral, popliteal and distal arteries sequential by-pass grafting was used to improve distal runoff. During a 5 year period (1988-1992), 53 sequential by passes were performed in 52 patients with severe ischemia manifested by rest pain (17) or trophic lesions (36). Autogenous saphenous vein was used in 36 (10 reversed, 26 in-situ), homologous saphenous in 3 and composite (PTFE+saphenous) in 14. Proximal anastomosis was performed on 29 common femoral, 20 superficial femoral and 4 popliteal arteries. Intermediary anastomosis was performed on 6 above-knee and 31 below-knee popliteal arteries and on 16 distal arteries. All distal anastomoses were performed on distal arteries (13 cases on malleolar arteries). The mean follow-up was 18 months. Thirteen patients died during this period (mean 8.5 months after the surgery). Primary and secondary patency were respectively 66 and 79% over one year and 51 and 76% over two years. Limb salvage was obtained in 89% over one year and 86% over 2 years. Sequential by-pass is a useful alternative for limb salvage. This approach offers several hemodynamic advantages and may be the best procedure in patients with poor distal runoff. PMID- 8195269 TI - Intraoperative whole blood autotransfusion during venous thrombectomy. AB - OBJECTIVE: Intraoperative autotransfusion is currently performed using two different systems, the relatively expensive cell-saving device washes and concentrates red cells and the more simple, economical total disposable device for whole blood collection and retransfusion. Some institutions prefer the cell saving device because of previously documented side-effects of whole blood autotransfusion. As some investigators more recently reported the application of whole blood autotransfusion without clinical complications, the potential hazards of whole blood autotransfusion are now being controversially discussed. MATERIALS AND METHODS: The potential side-effects using whole blood autotransfusion were studied in 100 patients prospectively undergoing venous thrombectomy. The effectiveness of homologous transfusion reduction was assessed in comparison with an historical patient group (n = 10, control group). RESULTS: In the study population a mean of 1064 ml shed blood (67% of total blood loss) was retransfused. A mean of 247 +/- 292 ml of homologous blood was transfused in the study group. In contrast, homologous blood requirement was significantly higher (1056 +/- 659 ml, p < 0.006) in the control group. No hematologic, hemeostatic, renal or pulmonary complications occurred after intraoperative whole blood autotransfusion. CONCLUSIONS: Whole blood autotransfusion is a safe, easy and economical procedure and highly effective in reducing homologous blood transfusions and costs. PMID- 8195270 TI - Abdominal aneurysmectomy and determinants of improved results and late survival. Surgical considerations in 672 operations and 1-15 year follow-up. AB - The present communication is concerned with 672 abdominal aneurysmectomies performed over a period of 24 years. All aneurysms with diameter 4 cm and above, were considered for surgery. Emphasis is given on factors determining post operative results and late survival. There was an age ranging from 38 to 92 years (mean 68.3). Elective surgery was performed in 434 cases with mortality 2.8%. In 100 symptomatic patients mortality was 4%. In 115 cases emergency undertaking was necessary. From this particular group, 80 cases represent formal rupture with mortality 41%. In the remaining 35 patients with symptomatology compatible with "impending rupture" mortality was 6%. There were 5 cases with inflammatory aneurysm with no incidence of death and 18 with simultaneous renal reconstruction. Mortality in the latter group was 11%. Risk factors including heart disease, hypertension and other associated pathology, were responsible for the majority of early deaths within the period of 30 post operative days and late mortality. Concerning late deaths, cardiac cases were predominant (24%), followed by cerebrovascular insufficiency (8%), cancer (5%) and chronic pulmonary disease (6%). In the overall follow-up, parameters such as hypertension with and/or without associated heart disease, symptomatology due to aneurysm and other associated pathology, were comparatively used in selective group of patients. Late mortality was investigated among three groups of patients and classified according to the 60, 70 and 80 decade of life. An entry form listing pertinent data was constructed and completed on the base of direct information from 489 (72.7%) and indirect from 183 (27.3%) patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195271 TI - Subclinical arteriosclerosis screening. The PAP/PEA study. Prevalenza dell'Arteriosclerosi Precoce (Prevalence of Early Arteriosclerosis). AB - Noninvasive screening of subclinical atherosclerosis is possible with ultrasonic biopsy (UB) performed with high resolution ultrasound scanning. Five UB classes have been identified, each class corresponding to a different incidence of cardiovascular events (CVE) in 4 years and silent coronary ischemia (SCI). In a study including 2230 asymptomatic subjects 3 risk groups were defined. In the low risk group (class I and II; 82.01% of the population sample) the incidence of CVE and SCI was zero. These subjects may be seen again after 3 years. In the moderate risk group (class II and IV; 13.3%) monitoring and early intervention may be needed. In the high risk group (class V; 4.6%) prophylaxis or treatment may be necessary. The screening is effective, simple and may be organised at very low cost--i.e. 30.000 asymptomatic subjects may be scanned at the cost of 100.000 ECU. Each scan, including carotid and femoral bifurcations, may be performed in 15 minutes. In our communities this cost is equivalent to the average cost of a single major stroke or major coronary ischemic event in a working adult aging between 45 and 60. Organization problems and the fragmentation of competences has prevented the evolution of atherosclerosis screening. The problem can be solved organising a network including epidemiologists, angiologists and cardiovascular surgical centres where all phases of atherosclerosis may be studied and detected, progression prevented and complications treated with a global vision of the disease. PMID- 8195272 TI - Late survival up to 20 years after isolated coronary by-pass surgery using internal mammary artery in patients with severe left ventricular dysfunction. AB - Coronary patients with left ventricular ejection fraction (LVEF) < 40% and abnormal motion of all left ventricular walls on cineangiography but without significant valve disease or left ventricular aneurysm were selected for this study. From January 1970 to December 1990, 155 patients meeting the above criteria consecutively underwent coronary by-pass surgery; preoperatively, 149 patients had angina class III or IV, and 49 patients had dyspnea class II or III. LVEF was 31 +/- 7%. During this 20-year period, two different surgical techniques have been used: from 1970 to 1981, 79 patients (group I) received internal mammary artery upon left anterior descending artery with associated simple saphenous grafts, under intermittent aortic cross clamping; from 1982 to 1990, 76 patients (group II) received internal mammary artery upon left anterior descending artery with associated sequential saphenous vein graft, under oxygenated cardioplegic myocardial protection. The mean number of by-pass was 1.6 in group I and 3.7 in group II (p = 0.001). Early mortality rate was lower in group II than in group I: 2.6% vs 7.6% (p = 0.01). After a follow-up of 79 +/- 14 months, there were 51 late deaths, 6 patients were lost to follow-up and 90 patients were still alive; 80% of all deaths were from cardiac causes, including 38% due to heart failure. Actuarial survival rate at 5, 10, 15 years was 79 +/- 7%, 63 +/- 10%, and 36 +/- 15% respectively. The 5-year survival rate was 71 +/- 10% in group I and 88 +/- 8% in group II (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195273 TI - Ruptured aneurysms of the sinus of Valsalva. AB - Sixteen patients underwent operation for ruptured aneurysm of the sinus of Valsalva (RASV) between 1979 and 1992. The age ranged from nine to 57 years (mean 31.8 years). Four patients were asymptomatic and 12 symptomatic and among symptomatic patients, five patients underwent emergency operation. Associated congenital anomalies were subpulmonary ventricular septal defect in 11 patients and infundibular pulmonary stenosis in one patient. Aortic regurgitation (AR) was mild in four, moderate in two, and severe in five. Surgical approach for RASV was a double incision for 12 patients (incision of ascending aorta and pulmonary artery, seven; that of ascending aorta and right ventricle, five), and single incision in four (pulmonary artery, three; right ventricle, one). Concomitant aortic surgery was performed in seven patients: aortic valve replacement (AVR), six and aortic valvuloplasty, one. One patient with emergency operation after cardiac arrest died one day after operation, while four emergency and 11 elective patients were uneventful after operation. In a follow up period of a mean of 90.3 months, there were no leaks of VSD closure and no recurrence of aneurysm. In 10 patients without AVR, mild AR remained in two, while the others showed no AR. The New York Heart Association functional class after operation was class I for 14 and class II for one. It seems that RASV requires early examination and operation to prevent an acute deterioration of symptoms and AR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195274 TI - Pathologic findings in 74 dysfunctional Braile-Biomedica bovine pericardial heart valves recovered at reoperation, 1978 to 1990. AB - This report describes the morphological data obtained from 74 Braile-Biomedica bovine pericardial valves (previously named IMC bovine pericardial valve) recovered at reoperation in our institution between 1978 and 1990. This retrospective analysis allowed for a thorough evaluation of the pathologic findings after long-term implantation of the Braile-Biomedica pericardial xenograft. The major cause of valve failure was pericardial tissue calcification, causing cuspal stiffening or structural defect responsible for clinical symptoms of stenosis and/or regurgitation. Our results demonstrated calcification in 65% of the explanted bioprostheses. Calcific deposits were most extensive in the tunica fibrosa of the pericardium, more prevalent in patients less than 30 years old at the time of implantation, and in valves implanted in the mitral position. Mild to moderate degenerative changes of the native pericardium were observed. No differences between men and women could be detected. Endocarditis was the second most frequent cause of xenograft failure (16%). Cuspal tears, contrasting with previous reports on the pathological features in clinically failed pericardial valves, were relatively infrequent (6.8%). Two valves explanted (2.7%) because clinical manifestation of valvular incompetence showed marked degenerative changes of the pericardial native tissue as the only findings. These observations, very similar to those reported for porcine aortic valves, complement and give support to previously published data on the satisfactory clinical performance of the Braile-Biomedica pericardial bioprosthesis. The discrepancy between the present observations and those reported by other authors on different types of pericardial valves, reinforces the opinion that these pericardial bioprostheses should not be studied as an unified group, the results and conclusions must be specific for each one of them. PMID- 8195275 TI - Oxygen free radicals in erythrocytes during open heart operation. AB - This study was performed to observe the effect of myocardial ischemia on the patients undergoing cardiopulmonary bypass (CPB) operation. For this aim, superoxide dismutase (SOD) activities, reduced glutathione (GSH) and lipid peroxide (LP) levels were determined in blood samples which were obtained from the coronary sinus. Sampling times were as follows: (1) Before CPB. (2) Immediately after CPB. (3) Fifteen minutes after the second specimen. (4) Thirty minutes after the second specimen. SOD activities of these groups were 5135.10 +/ 278.51 U/g Hb, 3505.64 +/- 302.09 U/g Hb, 4206.55 +/- 272.25 U/g Hb, 4707.20 +/- 270.91 U/g Hb respectively. Also the LP levels were 1.90 +/- 0.29 nmol MDA/ml, 4.37 +/- 0.52 nmol MDA/ml, 4.09 +/- 0.39 nmol MDA/ml, 2.74 +/- 0.30 nmol MDA/ml respectively. GSH levels were slightly increased during ischemia and reperfusion; 103.27 +/- 5.18 mg/dl, 125.00 +/- 10.36 mg/dl, 125.00 +/- 6.61 mg/dl, 111.18 +/- 8.22 mg/dl respectively. SOD activities were reduced significantly in second group (p < 0.001), in third and fourth groups (p < 0.01) as compared with control group. Also LP levels were increased significantly in all groups (p < 0.001) as compared with controls. Our results confirm the generation of oxygen free radicals from ischemia and reperfusion of heart during CPB. Also it appears that oxygen free radical generation exceeds the capacity of intracellular SOD, which is the most important scavenger of free radical in the cell. PMID- 8195276 TI - The role of open lung biopsy in early and late survival of ventilator-dependent patients with diffuse idiopathic lung disease. AB - Because of the high mortality associated with a diagnostic open lung biopsy in patients on mechanical ventilatory support, the clinical benefits of this procedure remain controversial. To assess the surgical results and the usefulness of open lung biopsies performed in this subset of patients, the clinical records of 27 patients who underwent open lung biopsy between January, 1987 and December, 1992 were reviewed. All patients were intubated for respiratory failure of unknown origin and were treated with antibiotics and/or steroids prior to the open lung biopsy. There were 13 men and 14 women with the mean age of 51 +/- 4.7 years (3 mos. to 82 years). The average duration for ventilatory support was 9 +/ 3.7 days (1 to 98 days). Nonoperative invasive diagnostic procedures were performed in 19 patients (70%). The operative approach for biopsy was an anterolateral thoracotomy using a linear stapler: right in 10 patients (37%), left in 17 (63%). A specific histologic diagnosis with open lung biopsy was established in all patients. Based on the biopsy findings, a change in treatment was unnecessary in 9 patients (33%), the dose of corticosteroids was increased in 7 (26%), the corticosteroids were initiated in 6 (22%), and a new antibiotic was added in 5 (19%). Perioperative complications occurred in 11 patients (40%). Prolonged air leak was the most common complication (6/11 patients). Fourteen patients (52%) died within 30 days of the biopsy procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195277 TI - Bronchial sleeve resection distal to the main bronchi with complete pulmonary preservation. Report on three successful cases. AB - Three successful cases of low grade malignant bronchial tumors resected by means of a bronchial sleeve resection distal to the main bronchi with complete pulmonary preservation are presented. Reconstruction of the bronchial tree was accomplished by suturing together the distal lobar bronchi and then anastomosing the double-barrel suture to the proximal residual bronchus. All patients presented excellent results, although in one patient postoperative course was complicated by persistent mucopurulent secretions. Bronchial sleeve resection distal to the main bronchi can be successfully performed for benign or low-grade malignant bronchial tumors. Technically, the operation is more complex than standard sleeve resection of the main bronchus and requires an experienced team. Postoperatively, an increased morbidity rate, mostly represented by secretions retention, may usually be anticipated, necessitating an aggressive medical and bronchoscopic management. PMID- 8195278 TI - New trends in the postoperative management of cardiac surgical patients. A review. PMID- 8195279 TI - Disruption of the expanded polytetrafluoroethylene (EPTFE) graft of axillofemoral by-pass. AB - The rupture of the artificial vascular graft is a rare complication. The disruption of the expanded polytetrafluoroethylene (EPTFE) graft has never been reported. The present report describes a patient who suffered the disruption of an EPTFE graft five years after a right axillofemoral by-pass. PMID- 8195280 TI - Superior mesenteric artery emboli during renal PTA: successful surgical treatment after fibrinolysis failure. AB - The paper presents a rare case of iatrogenic embolization of the superior mesenteric artery which required an emergency operation after an unsuccessful fibrinolytic treatment. An old woman, who had undergone renal percutaneous angioplasty (r-PTA), presented sudden but transient abdominal pain. Angiographic control of the angioplasty showed the goal of r-PTA but also an embolic occlusion of the main trunk of the superior mesenteric artery that did not respond to a selective fibrinolytic treatment. Within a few hours, the abdominal pain appeared again and induced an exploratory laparotomy which showed an extensive ischaemia of the whole jejunum. A successful embolectomy was performed associated with the resection of about 20 cm of necrotic jejunum. The postoperative period was uncomplicated. The case underlines several topics: close collaboration is necessary between interventional radiologists and surgeons in order to get a surgical "stand-by" during PTA procedures; the embolic occlusion of the superior mesenteric artery can produce irreversible, even if segmentary intestinal damage, also within a very short time after onset and, therefore, it seems to be at high risk for a fibrinolytic approach. PMID- 8195281 TI - Delayed sequelae of penetrating chest trauma: a plea for early sternotomy. AB - Penetrating wounds of the anterior chest wall are often associated with cardiac tamponade. Eighty to ninety percent of stab wounds to the heart result in acute tamponade, whereas delayed cardiac tamponade or hemothorax are rare, but hurtful for the patient. Of the cases reviewed, fifty percent of the patients who underwent sternotomy required repair of cardiac injuries. The presented case report adds further justification for early sternotomy in case of precordial penetrating chest injury in the danger zone. PMID- 8195282 TI - Rupture of gastroepiploic-coronary bypass graft due to cardiopulmonary resuscitation. PMID- 8195283 TI - Medlars for searching correct references. PMID- 8195284 TI - The small abdominal aortic aneurysm: the eternal dilemma. AB - In order to evaluate morbidity and mortality after elective resection of abdominal aortic aneurysms (AAA) as it relates to aneurysm size, a retrospective review of 111 elective aneurysmectomies over a 5 year period was undertaken in a VA population. Thirty seven AAA's measured < 5 cm in diameter and 74 were > or = 5 cm by CT scan. Patients with small AAA (S-AAA) were significantly younger (mean 64 years) than those with large AAA (L-AAA) (mean 69 years) (p < 0.003). Both groups were similar with respect to prevalence of cardiovascular, pulmonary and renal disease. Aortic cross-clamping time was significantly shorter in L-AAA, possibly because those with S-AAA had a higher prevalence of associated occlusive disease requiring more femoral anastomoses (p < 0.04). Postoperatively six patients (8%) had a myocardial infarction (MI) in the L-AAA group and four (5%) of these died. In contrast no patient with S-AAA suffered a postoperative MI. The rates of non-cardiac complications and length of hospital stay were not significantly different between the two groups. However, the patients with L-AAA stayed longer in ICU (p < 0.05) and the overall combined morbidity rate was significantly higher in this group (p < 0.02). Our results suggest that resection of S-AAA upon diagnosis in acceptable risk patients appears to be the safest overall therapeutic plan. PMID- 8195285 TI - Tetanus toxin-mediated cleavage of cellubrevin impairs exocytosis of transferrin receptor-containing vesicles in CHO cells. AB - Cellubrevin is a member of the synaptobrevin/VAMP family of SNAREs, which has a broad tissue distribution. In fibroblastic cells it is concentrated in the vesicles which recycle transferrin receptors but its role in membrane trafficking and fusion remains to be demonstrated. Cellubrevin, like the synaptic vesicle proteins synaptobrevins I and II, can be cleaved by tetanus toxin, a metallo endoprotease which blocks neurotransmitter release. However, nonneuronal cells are unaffected by the toxin due to lack of cell surface receptors for its heavy chain. To determine whether cellubrevin cleavage impairs exocytosis of recycling vesicles, we tested the effect of tetanus toxin light chain on the release of preinternalized transferrin from streptolysin-O-perforated CHO cells. The release was found to be temperature and ATP dependent as well as NEM sensitive. Addition of tetanus toxin light chain, but not of a proteolytically inactive form of the toxin, resulted in a partial inhibition of transferrin release which correlated with the toxin-mediated cleavage of cellubrevin. The residual release of transferrin occurring after complete cellubrevin degradation was still ATP dependent. Our results indicate that cellubrevin plays an important role in the constitutive exocytosis of vesicles which recycle plasmalemma receptors. The incomplete inhibition of transferrin release produced by the toxin suggests the existence of a cellubrevin-independent exocytotic mechanism, which may involve tetanus toxin-insensitive proteins of the synaptobrevin/VAMP family. PMID- 8195286 TI - Basolateral protein transport in streptolysin O-permeabilized MDCK cells. AB - We have reconstituted polarized protein transport in streptolysin O-permeabilized MDCK cells from the TGN to the basolateral surface and to the apical surface. These transport steps are dependent on temperature, energy and exogenously supplied cytosol. Using this in vitro system we show that a whole tail peptide (WT peptide) corresponding to the cytoplasmic tail of a basolaterally sorted protein, the vesicular stomatitis virus glycoprotein (VSV G) inhibits the TGN to basolateral transport but does not affect any other transport step. Inhibition of VSV G transport to basolateral surface by WT peptide did not result in missorting of the protein to the apical surface. Mutation of the single tyrosine residue in the WT peptide reduced its inhibitory potency four- to fivefold. These results suggest that the VSV G tail physically interacts with a component of the sorting machinery. Using a cross-linking approach, we have identified proteins that associate with the cytoplasmic tail domain of VSV G. One of these polypeptides, Tin-2 (Tail interacting protein-2), associates with VSV G in the TGN, the site of protein sorting, but not in the ER nor at the cell surface. Tin-2 does not associate with apically targeted hemagglutinin. WT peptide that inhibited the basolateral transport of VSV G also inhibited the association of Tin-2 with VSV G. Together, these properties make Tin-2 a candidate basolateral sorter. The results demonstrate the usefulness of the SLO-permeabilized cell system in dissecting the sorting machinery. PMID- 8195287 TI - Involvement of 70-kD heat-shock proteins in peroxisomal import. AB - This report describes the involvement of 70-kD heat-shock proteins (hsp70) in the import of proteins into mammalian peroxisomes. Employing a microinjection-based assay (Walton, P. A., S. J. Gould, J. R. Feramisco, and S. Subramani. 1992. Mol. Cell Biol. 12:531-541), we demonstrate that proteins of the hsp70 family were associated with proteins being imported into the peroxisomal matrix. Import of peroxisomal proteins could be inhibited by coinjection of antibodies directed against the constitutive hsp70 proteins (hsp73). In a permeabilized-cell assay (Wendland and Subramani. 1993. J. Cell Biol. 120:675-685), antibodies directed against hsp70 proteins were shown to inhibit peroxisomal protein import. Inhibition could be overcome by the addition of exogenous hsp70 proteins. Purified rat liver peroxisomes were shown to have associated hsp70 proteins. The amount of associated hsp70 was increased under conditions of peroxisomal proliferation. Furthermore, proteinase protection assays indicated that the hsp70 molecules were located on the outside of the peroxisomal membrane. Finally, the process of heat-shocking cells resulted in a considerable delay in the import of peroxisomal proteins. Taken together, these results indicate that heat-shock proteins of the cytoplasmic hsp70 family are involved in the import of peroxisomal proteins. PMID- 8195288 TI - Yolk platelets in Xenopus oocytes maintain an acidic internal pH which may be essential for sodium accumulation. AB - Yolk platelets constitute an embryonic endocytic compartment that stores maternally synthesized nutrients. The pH of Xenopus yolk platelets, measured by photometry on whole oocytes which had endocytosed FITC-vitellogenin, was found to be acidic (around pH 5.6). Experiments on digitonin-permeabilized oocytes showed that acidification was due to the activity of an NEM- and bafilomycin A1 sensitive vacuolar proton-ATPase. Proton pumping required chloride, but was not influenced by potassium or sodium. Passive proton leakage was slow, probably due to the buffer capacity of the yolk, and was dependent on the presence of cytoplasmic monovalent cations. In particular, sodium could drive proton efflux through an amiloride-sensitive Na+/H+ exchanger. 8-Bromo-cyclic-AMP was found to increase acidification, suggesting that pH can be regulated by intracellular second messengers. The moderately acidic pH does not promote degradation of the yolk platelets, which in oocytes are stable for weeks, but it is likely to be required to maintain the integrity of these organelles. Furthermore, the pH gradient created by the proton pump, when coupled with the Na+/H+ exchanger, is probably responsible for the accumulation and storage of sodium into the yolk platelets during oogenesis. PMID- 8195289 TI - Rapid capping in alpha-spectrin-deficient MEL cells from mice afflicted with hereditary hemolytic anemia. AB - A spectrin-based membrane skeleton is important for the stability and organization of the erythrocyte. To study the role of spectrin in cells that possess complex cytoskeletons, we have generated alpha-spectrin-deficient erythroleukemia cell lines from sph/sph mice. These cells contain beta-spectrin, but lack alpha-spectrin as determined by immunoblot and Northern blot analyses. The effects of alpha-spectrin deficiency are apparent in the cells' irregular shape and fragility in culture. Capping of membrane glycoproteins by fluorescent lectin or antibodies occurs more rapidly in sph/sph than in wild-type erythroleukemia cells, and the caps appear more concentrated. The data support the idea that spectrin plays an important role in organizing membrane structure and limiting the lateral mobility of integral membrane glycoproteins in cells other than mature erythrocytes. PMID- 8195290 TI - Interactions of tensin with actin and identification of its three distinct actin binding domains. AB - Tensin, a 200-kD phosphoprotein of focal contacts, contains sequence homologies to Src (SH2 domain), and several actin-binding proteins. These features suggest that tensin may link the cell membrane to the cytoskeleton and respond directly to tyrosine kinase signalling pathways. Here we identify three distinct actin binding domains within tensin. Recombinant tensin purified after overexpression by a baculovirus system binds to actin filaments with Kd = 0.1 microM, cross links actin filaments at a molar ratio of 1:10 (tensin/actin), and retards actin assembly by barbed end capping with Kd = 20 nM. Tensin fragments were constructed and expressed as fusion proteins to map domains having these activities. Three regions from tensin interact with actin: two regions composed of amino acids 1 to 263 and 263 to 463, cosediment with F-actin but do not alter the kinetics of actin assembly; a region composed of amino acids 888-989, with sequence homology to insertin, retards actin polymerization. A claw-shaped tensin dimer would have six potential actin-binding sites and could embrace the ends of two actin filaments at focal contacts. PMID- 8195292 TI - Mutations in the "dynein regulatory complex" alter the ATP-insensitive binding sites for inner arm dyneins in Chlamydomonas axonemes. AB - To understand mechanisms of regulation of dynein activity along and around the axoneme we further characterized the "dynein regulatory complex" (drc). The lack of some axonemal proteins, which together are referred to as drc, causes the suppression of flagellar paralysis of radial spoke and central pair mutants. The drc is also an adapter involved in the ATP-insensitive binding of I2 and I3 inner dynein arms to doublet microtubules. Evidence supporting these conclusions was obtained through analyses of five drc mutants: pf2, pf3, suppf3, suppf4, and suppf5. Axonemes from drc mutants lack part of I2 and I3 inner dynein arms as well as subsets of seven drc components (apparent molecular weight from 29,000 to 192,000). In the absence of ATP-Mg, dynein-depleted axonemes from the same mutants bind I2 and I3 inner arms at both ATP-sensitive and -insensitive sites. At ATP-insensitive sites, they bind I2 and I3 inner arms to an extent that depends on the drc defect. This evidence suggested to us that the drc forms one binding site for the I2 and I3 inner arms on the A part of doublet microtubules. PMID- 8195291 TI - Growth site localization of Rho1 small GTP-binding protein and its involvement in bud formation in Saccharomyces cerevisiae. AB - The Rho small GTP-binding protein family regulates various actomyosin-dependent cell functions, such as cell morphology, locomotion, cytokinesis, membrane ruffling, and smooth muscle contraction. In the yeast Saccharomyces cerevisiae, there is a homologue of mammalian RhoA, RHO1, which is essential for vegetative growth of yeast cells. To explore the function of the RHO1 gene, we isolated a recessive temperature-sensitive mutation of RHO1, rho1-104. The rho1-104 mutation caused amino acid substitutions of Asp 72 to Asn and Cys 164 to Tyr of Rho1p. Strains bearing the rho1-104 mutation accumulated tiny- or small-budded cells in which cortical actin patches were clustered to buds at the restrictive temperature. Cell lysis and cell death were also seen with the rho1-104 mutant. Indirect immunofluorescence microscopic study demonstrated that Rho1p was concentrated to the periphery of the cells where cortical actin patches were clustered, including the site of bud emergence, the tip of the growing buds, and the mother-bud neck region of cells prior to cytokinesis. Indirect immunofluorescence study with cells overexpressing RHO1 suggested that the Rho1p binding site was saturable. A mutant Rho1p with an amino acid substitution at the lipid modification site remained in the cytoplasm. These results suggest that Rho1 small GTP-binding protein binds to a specific site at the growth region of cells, where Rho1p exerts its function in controlling cell growth. PMID- 8195293 TI - On the localization of voltage-sensitive calcium channels in the flagella of Chlamydomonas reinhardtii. AB - This study was undertaken to prove that voltage-sensitive calcium channels controlling the photophobic stop response of the unicellular green alga Chlamydomonas reinhardtii are exclusively found in the flagellar region of the cell and to answer the question as to their exact localization within the flagellar membrane. The strategy used was to amputate flagella to a variable degree without perturbing the electrical properties of the cell and measure flagellar currents shortly after amputation and during the subsequent regeneration process. Under all conditions, a close correlation was found between current size and flagellar length, strongly suggesting that the channels that mediate increases in intraflagellar calcium concentration are confined to and distributed over the total flagellar length. Bald mutants yielded tiny flagellar currents, in agreement with the existence of residual flagellar stubs. In the presence of the protein synthesis inhibitor cycloheximide, flagellar length and flagellar currents also recovered in parallel. Recovery came to an earlier end, however, leveling off at a time when in the absence of cycloheximide only half maximal values were achieved. This suggests the existence of a pool of precursors, which permits the maintenance of a constant ratio between voltage sensitive calcium channels and other intraflagellar proteins. PMID- 8195294 TI - Visualization of calcium transients controlling orientation of ciliary beat. AB - To image changes in intraciliary Ca controlling ciliary motility, we microinjected Ca Green dextran, a visible wavelength fluorescent Ca indicator, into eggs or two cell stages of the ctenophore Mnemiopsis leidyi. The embryos developed normally into free-swimming, approximately 0.5 mm cydippid larvae with cells and ciliary comb plates (approximately 100 microns long) loaded with the dye. Comb plates of larvae, like those of adult ctenophores, undergo spontaneous or electrically stimulated reversal of beat direction, triggered by Ca influx through voltage-sensitive Ca channels. Comb plates of larvae loaded with Ca Green dextran emit spontaneous or electrically stimulated fluorescent flashes along the entire length of their cilia, correlated with ciliary reversal. Fluorescence intensity peaks rapidly (34-50 ms), then slowly falls to resting level in approximately 1 s. Electrically stimulated Ca Green emissions often increase in steps to a maximum value near the end of the stimulus pulse train, and slowly decline in 1-2 s. In both spontaneous and electrically stimulated flashes, measurements at multiple sites along a single comb plate show that Ca Green fluorescence rises within 17 ms (1 video field) and to a similar relative extent above resting level from base to tip of the cilia. The decline of fluorescence intensity also begins simultaneously and proceeds at similar rates along the ciliary length. Ca-free sea water reversibly abolishes spontaneous and electrically stimulated Ca Green ciliary emissions as well as reversed beating. Calculations of Ca diffusion from the ciliary base show that Ca must enter the comb plate along the entire length of the ciliary membranes. The voltage dependent Ca channels mediating changes in beat direction are therefore distributed over the length of the comb plate cilia. The observed rapid and virtually instantaneous Ca signal throughout the intraciliary space may be necessary for reprogramming the pattern of dynein activity responsible for reorientation of the ciliary beat cycle. PMID- 8195295 TI - Transformation by myc prevents fusion but not biochemical differentiation of C2C12 myoblasts: mechanisms of phenotypic correction in mixed culture with normal cells. AB - To study the effects of myc oncogene on muscle differentiation, we infected the murine skeletal muscle cell line C2C12 with retroviral vectors encoding various forms of avian c- or v-myc oncogene. myc expression induced cell transformation but, unlike many other oncogenes, prevented neither biochemical differentiation, nor commitment (irreversible withdrawal from the cell cycle). Yet, myotube formation by fusion of differentiated cells was strongly inhibited. Comparison of uninfected C2C12 myotubes with differentiated myc-expressing C2C12 did not reveal consistent differences in the expression of several muscle regulatory or structural genes. The present results lead us to conclude that transformation by myc is compatible with differentiation in C2C12 cells. myc expression induced cell death under growth restricting conditions. Differentiated cells escaped cell death despite continuing expression of myc, suggesting that the muscle differentiation programme interferes with the mechanism of myc-induced cell death. Cocultivation of v-myc-transformed C2C12 cells with normal fibroblasts or myoblasts restored fusion competence and revealed two distinguishable mechanisms that lead to correction of the fusion defect. PMID- 8195296 TI - Evidence for an interplay between cell cycle progression and the initiation of differentiation between life cycle forms of African trypanosomes. AB - Successful transmission of the African trypanosome between the mammalian host blood-stream and the tsetse fly vector involves dramatic alterations in the parasite's morphology and biochemistry. This differentiation through to the tsetse midgut procyclic form is accompanied by re-entry into a proliferative cell cycle. Using a synchronous differentiation model and a variety of markers diagnostic for progress through both differentiation and the cell cycle, we have investigated the interplay between these two processes. Our results implicate a relationship between the trypanosome cell cycle position and the perception of the differentiation signal and demonstrate that irreversible commitment to the differentiation occurs rapidly after induction. Furthermore, we show that re entry into the cell cycle in the differentiating population is synchronous, and that once initiated, progress through the differentiation pathway can be uncoupled from progress through the cell cycle. PMID- 8195297 TI - A hyaluronidase activity of the sperm plasma membrane protein PH-20 enables sperm to penetrate the cumulus cell layer surrounding the egg. AB - A typical mammalian egg is surrounded by an outer layer of about 3,000 cumulus cells embedded in an extracellular matrix rich in hyaluronic acid. A current, widely proposed model is that the fertilizing sperm, while it is acrosome intact, passes through the cumulus cell layer and binds to the egg zona pellucida. This current model lacks a well-supported explanation for how sperm penetrate the cumulus layer. We report that the sperm protein PH-20 has a hyaluronidase activity and is present on the plasma membrane of mouse and human sperm. Brief treatment with purified, recombinant PH-20 can release all the cumulus cells surrounding mouse eggs. Acrosome intact mouse sperm incubated with anti-PH-20 antibodies can not pass through the cumulus layer and thus can not reach the zona pellucida. These results, indicating that PH-20 enables acrosome intact sperm to penetrate the cumulus barrier, reveal a mechanism for cumulus penetration, and thus provide the missing element in the current model. PMID- 8195298 TI - Mapping the heparin-binding sites on type I collagen monomers and fibrils. AB - The glycosaminoglycan chains of cell surface heparan sulfate proteoglycans are believed to regulate cell adhesion, proliferation, and extracellular matrix assembly, through their interactions with heparin-binding proteins (for review see Ruoslahti, E. 1988. Annu. Rev. Cell Biol. 4:229-255; and Bernfield, M., R. Kokenyesi, M. Kato, M. T. Hinkes, J. Spring, R. L. Gallo, and E. J. Lose. 1992. Annu. Rev. Cell Biol. 8:365-393). Heparin-binding sites on many extracellular matrix proteins have been described; however, the heparin-binding site on type I collagen, a ubiquitous heparin-binding protein of the extracellular matrix, remains undescribed. Here we used heparin, a structural and functional analogue of heparan sulfate, as a probe to study the nature of the heparan sulfate proteoglycan-binding site on type I collagen. We used affinity coelectrophoresis to study the binding of heparin to various forms of type I collagen, and electron microscopy to visualize the site(s) of interaction of heparin with type I collagen monomers and fibrils. Using affinity coelectrophoresis it was found that heparin has similar affinities for both procollagen and collagen fibrils (Kd's approximately 60-80 nM), suggesting that functionally similar heparin-binding sites exist in type I collagen independent of its aggregation state. Complexes of heparin-albumin-gold particles and procollagen were visualized by rotary shadowing and electron microscopy, and a preferred site of heparin binding was observed near the NH2 terminus of procollagen. Native or reconstituted type I collagen fibrils showed one region of significant heparin-gold binding within each 67-nm period, present near the division between the overlap and gap zones, within the "a" bands region. According to an accepted model of collagen fibril structure, our data are consistent with the presence of a single preferred heparin-binding site near the NH2 terminus of the collagen monomer. Correlating these data with known type I collagen sequences, we suggest that the heparin binding site in type I collagen may consist of a highly basic triple helical domain, including several amino acids known sometimes to function as disaccharide acceptor sites. We propose that the heparin-binding site of type I collagen may play a key role in cell adhesion and migration within connective tissues, or in the cell-directed assembly or restructuring of the collagenous extracellular matrix. PMID- 8195300 TI - Nuclear transport of U1 snRNP in somatic cells: differences in signal requirement compared with Xenopus laevis oocytes. AB - The signal requirement for the nuclear import of U1 RNA in somatic cells from different species was investigated by microinjection of both digoxygenin-labeled wild type and mutant U1 RNA molecules and in vitro reconstituted U1 snRNPs. U1 RNA was shown to be targeted to the nucleus by a temperature-dependent process that requires the prior assembly of RNPs from the common proteins and the microinjected RNA. Competition in the cell between immunoaffinity-purified U1 snRNPs and digoxygenin-labeled U1 snRNPs reconstituted in vitro showed that the transport is saturable and should therefore be a mediated process. The transport of a karyophilic protein under the same conditions was not affected, indicating the existence of a U snRNP-specific transport pathway in somatic cells, as already seen in the Xenopus laevis oocyte system. Surprisingly, the signal requirement for nuclear transport of U1 snRNP was found to differ between oocytes and somatic cells from mouse, monkey and Xenopus, in that the m3GGpppG-cap is no longer an essential signaling component in somatic cells. However, as shown by investigation of the transport kinetics of m3GpppG- and ApppG-capped U1 snRNPs, the m3GpppG-cap accelerates the rate of U1 snRNP import significantly indicating that it has retained a signaling role for nuclear targeting of U1 snRNP in somatic cells. Moreover, our data strongly suggest that cell specific rather than species specific differences account for the differential m3G-cap requirement in nuclear import of U1 snRNPs. PMID- 8195299 TI - NUP145 encodes a novel yeast glycine-leucine-phenylalanine-glycine (GLFG) nucleoporin required for nuclear envelope structure. AB - We have isolated and characterized the gene encoding a fourth yeast glycine leucine-phenylalanine-glycine (GLFG) repeat nucleoporin with a calculated molecular mass of 145.3 kD, and therefore termed NUP145. The amino-terminal half of Nup145p is similar to two previously identified GLFG nucleoporins, Nup116p and Nup100p (Wente, S. R., M. P. Rout, and G. Blobel. 1992. J. Cell Biol. 119:705 723). A deletion/disruption in the amino-terminal half of NUP145 (nup145 delta N) had only a slight effect on cell growth at temperatures between 17 and 37 degrees C. However, immunofluorescence microscopy of nup145 delta N cells with antinucleoporin antibodies showed that the characteristic punctate nuclear staining normally seen in wild-type yeast cells was reduced, with the majority of the signal located in one or two intense spots at the nuclear periphery. Thin section electron microscopy analysis revealed the presence of what appeared to be successive herniations of the nuclear envelope forming grape-like structures at primarily one site on the nup145 delta N nuclei. These successive herniations contained numerous NPC-like structures, correlating to the limited bright patches of anti-nucleoporin immunofluorescence signal. In some cases the successive herniations were small. Occasionally, however, multi-lobulated nuclei were seen. We suggest that the ultrastructural phenotype of nup145 delta N cells is due to a defective interaction of nup145 delta N NPCs with the surrounding pore membrane domain of the nuclear envelope. We have also analyzed the synthetic lethal phenotypes among GLFG nucleoporin mutant alleles, and found that strains harboring nup116 and either nup100 or nup145 mutations were not viable. This, in combination with the morphological analysis, may reflect overlapping yet distinct roles for these three GLFG nucleoporins in NPC-nuclear envelope interactions. PMID- 8195301 TI - Analysis of the intracellular localization and assembly of Ro ribonucleoprotein particles by microinjection into Xenopus laevis oocytes. AB - Xenopus laevis oocytes have been used to determine the intracellular localization of components of Ro ribonucleoprotein particles (Ro RNPs) and to study the assembly of these RNA-protein complexes. Microinjection of the protein components of human Ro RNPs, i.e., La, Ro60, and Ro52, in X. laevis oocytes showed that all three proteins are able to enter the nucleus, albeit with different efficiencies. In contrast, the RNA components of human Ro RNPs (the Y RNAs) accumulate in the X. laevis cytoplasm upon injection. Localization studies performed at low temperatures indicated that both nuclear import of Ro RNP proteins and nuclear export of Y RNAs are mediated by active transport mechanisms. Immunoprecipitation experiments using monospecific anti-La and anti-Ro60 antibodies showed that the X. laevis La and Ro60 homologues were cross-reactive with the respective antibodies and that both X. laevis proteins were able to interact with human Y1 RNA. Further analyses indicated that: (a) association of X. laevis La and Ro60 with Y RNAs most likely takes place in the nucleus; (b) once formed, Ro RNPs are rapidly exported out of the nucleus; and (c) the association with La is lost during or shortly after nuclear export. PMID- 8195303 TI - The process of parenting in failure to thrive. PMID- 8195302 TI - A peripheral protein associated with the cis-Golgi network redistributes in the intermediate compartment upon brefeldin A treatment. AB - Human autoantibodies offer unique tools for the study of cellular constituents since they usually recognize highly conserved components, the most difficult to detect due to their low immunogenicity. The serum from a patient with Sjogren's syndrome (RM serum) showing a very high reactivity to the Golgi complex has been shown to immunoprecipitate and to immunodetect by Western blotting experiments a protein mol wt 210,000 (p210) that was shown to be peripheral and cytoplasmically disposed. A close examination of the p210 labeling revealed some differences with Golgi markers: RM serum staining was slightly more extensive than several Golgi markers and showed a discontinuous or granular appearance. Nocodazole induced a specific and early segregation of many p210-associated vesicles or tubules from Golgi apparatus. Upon brefeldin A treatment, p210 did not redistribute in the ER as did other Golgi proteins. In contrast, it exhibited a vesicular pattern reminiscent to that displayed by proteins residing in the intermediate compartment. Double staining immunofluorescence using the RM serum and the marker of the intermediate compartment, p58, revealed segregation of both proteins in control conditions but colocalization in BFA-treated cells. We have further demonstrated by combining different drug treatments that p210-containing elements in brefeldin A-treated cells belong indeed to the intermediate compartment. Experiments on brefeldin A recovery suggested that these p210 elements might play a role in reformation and repositioning of the Golgi apparatus. Ultrastructural localization performed by immunoperoxidase staining allowed us to establish that p210 interacted with the external side of an abundant tubulo-vesicular system on the cis side of the Golgi complex which extended to connecting structures and vesicles between saccules or stacks of cisternae, p210 appears to be a novel protein residing in the cis-Golgi network that may cycle between the Golgi apparatus and the intermediate compartment. PMID- 8195304 TI - Long-term-outcome for people with Down's syndrome. PMID- 8195305 TI - Reading attainment and juvenile delinquency. AB - Structural equation modelling was used with data from a longitudinal study of child development (N = 698) to examine relationships between early reading attainment and antisocial behaviour at ages 7 and 9 years and subsequent reading and delinquent behaviour in adolescence. While reading, analysed as a continuous variable, did not directly influence later delinquency, antisocial behaviour during the early school years was strongly predictive of delinquency at age 15 years, particularly for boys, and had a detrimental effect on reading. These findings were independent of social disadvantage, and were unchanged by adjusting reading scores for IQ. Reading disability at 9 years old, however, predicted conduct disorder at age 15 in boys. PMID- 8195306 TI - Individual differences in risk of child abuse by adolescent mothers: assessment in the perinatal period. AB - Abuse risk potential and parenting attitudes of 66 adolescent mothers were examined during the perinatal period using self-report instruments. Approximately one-half of the sample was considered to be at significant risk. Specific risk factors included distress, rigidity in parenting attitudes, and inappropriate expectations of children. Younger adolescents were at greater risk of abuse, advocated the use of physical punishment more strongly, and reported greater unhappiness than older adolescents. Teens reporting limited social support were also at greater risk for abuse. Low acceptance of the pregnancy was related to abuse potential for parenting, but not pregnant, adolescents. A history of maltreatment was related to self-reported problems with family members but not to overall risk. Implications for the prevention of abuse among adolescent mothers are discussed. PMID- 8195307 TI - Mother-child interactions and noncompliance in hyperactive boys with and without conduct problems. AB - Mother-child interaction, and parent ratings of child noncompliance and defiance among hyperactive boys with conduct problems (H/CP), hyperactive boys without conduct problems (H), and normal boys (N) were compared. Results indicated more negative mother-child interactions and more noncompliance in the H/CP group than in the other two groups. The H group was more noncompliant than normal children, but these groups showed no differences in defiance, nor in the behaviour of mothers. The implications of these findings in relation to the development of conduct problems in hyperactive children, treatment and research are discussed. PMID- 8195308 TI - Adjustment in middle childhood and early adolescence: links with earlier and contemporary sibling relationships. AB - The relation of individual differences in internalizing and externalizing behavior in middle childhood and early adolescence to children's concurrent sibling relationships and their mothers' mood, and to their sibling and mother child relationships in the preschool period was studied. Thirty-nine younger and 39 older siblings observed at home in the preschool period were studied 5 and 7 years later. Differences in adjustment were related to contemporary sibling relationships and maternal mood, and to sibling and mother-child interaction in the preschool period, even when mothers' current mood was taken into account. PMID- 8195309 TI - Family involvement in residential treatment of children with retardation: is there evidence of detachment? AB - Family involvement could be critical for successful residential treatment. Historically, however, out of home placement for children with mental retardation meant a severing of meaningful ties with their families. Today, families have greater involvement with pre-placement services and might be more involved in residential treatment as well. Families (N = 55) were interviewed twice, approximately one and two years after placement, to assess their involvement with the child and their reactions to placement. Contrary to previous findings, family involvement was high and stable; there was no evidence of behavioral detachment. Moreover, respondents primarily reported post-placement benefits to the family. Family emotional reactions were considered within a framework of "psychological tasks of placement". PMID- 8195310 TI - The family systems test: a comment on Gehring and Marti (1993). PMID- 8195311 TI - Children's family constructs and classification of mental disorders: different measurement approaches may yield different results. PMID- 8195312 TI - Immune activation during infancy in healthy humans. AB - Immune activity during infancy was investigated using blood samples from 30 neonates and 52 healthy infants between 2 and 15 months of age attending for immunization. The purpose of this study was to assess the total immune activity of T cells using soluble interleukin-2 receptor (IL-2R) and interferon-gamma concentrations. These were compared with the proportion of CD4 CD45RO-, IL-2R (CD25)-, and transferrin receptor (CD71)-positive peripheral blood lymphocytes. The median duration of breast-feeding and of introduction of solid feeds was 4.2 and 4.0 months, respectively. Compared to neonates, the mean +/- SE soluble IL-2R concentration peaked at 4 months of age (1670 +/- 94 vs 3060 +/- 252 U/ml; P < 0.0001), as did pooled interferon-gamma levels. The percentage of CD4 CD45RO T cells remained low and the proportion of activated peripheral blood lymphocytes decreased during infancy. We conclude that noncirculatory immune activity is increased during infancy and this is associated with weaning. PMID- 8195313 TI - Long-term persistence of selective IgA deficiency in healthy adults. AB - A follow-up study of 204 healthy blood donors with IgA deficiency, identified between 1971 and 1980, was carried out. Sera were initially screened by a double diffusion method and 182 were retested by a more sensitive haemagglutination inhibition method. A reexamination was performed in 1990 and, again, in 1991-1992 using an enzyme immunoassay (EIA) developed for the measurement of very low concentrations of IgA. The median follow-up period was 19 years, and in 159 (78%) subjects no serum IgA could be detected in any of the measurements. In 42 (21%) subjects, serum IgA was detectable (> 0.18 mg/L), but the level was below the lower limit of the reference range for adults (800 mg/L) and remained relatively constant. Three subjects showed minute amounts of IgA by EIA (0.2-3 mg/L) in one of the follow-up samples in 1990-1992, but the level was below the detection limit of the EIA (0.05 mg/L) in the other sample. Thus, not only does primary IgA deficiency appear to be permanent, but also lower than normal serum IgA levels remain the same in healthy adults. PMID- 8195315 TI - Half-life of polyreactive antibodies. AB - Monoclonal polyreactive antibodies bind to a variety of self and foreign antigens. In contrast, monoclonal monoreactive antibodies bind to a single or restricted number of known antigens. The rate at which polyreactive antibodies are removed from the circulation compared to monoreactive antibodies has not been determined. In the present experiments, human monoclonal polyreactive and monoreactive antibodies of different isotypes were injected intravenously into mice and the clearance from the circulation was determined. The half-life of polyreactive IgM, IgA, and IgG antibodies was 8.0, 8.2, and 9.8 hr, respectively, compared to 35.4, 26.6, and 280 hr for monoreactive IgM, IgA, and IgG antibodies, respectively. Examination of tissue sections from animals given intravenous antibody showed substantial deposition of polyreactive, but not monoreactive, antibodies in several organs, the liver being the principal site of deposition. It is concluded that polyreactive antibodies are cleared from the circulation substantially faster than monoreactive antibodies. PMID- 8195314 TI - The role of bactericidal/permeability-increasing protein in the treatment of primate bacteremia and septic shock. AB - Human neutrophil azurophilic granules contain an approximately 55-kDa protein, known as bactericidal/permeability-increasing protein (BPI), which possesses a high-affinity binding domain for the lipid A component of lipopolysaccharide (LPS). The in vivo LPS neutralizing activity of exogenous BPI was studied in a model of lethal Escherichia coli bacteremia. Five baboons were treated with BPI (5 mg/kg bolus injection followed by a 95 micrograms/kg/min BPI infusion over 4 hr), while four additional animals received a genetically engineered variant of BPI (NCY103). Five animals received a placebo treatment and served as controls. Both wild-type rhBPI and NCY103 significantly (P < 0.05) decreased blood levels of LPS throughout an 8-hr evaluation period following live bacterial challenge. Two hours following E. coli administration, LPS levels peaked in the controls, at 6.86 +/- 3.22 ng/ml, whereas LPS levels were 3.39 +/- 2.1 ng/ml in the BPI group and 2.04 +/- 1.18 ng/ml in the NCY103 group. Tumor necrosis factor-alpha (TNF alpha) and interleukin-6 levels likewise were attenuated in the treatment groups, whereas circulating sTNFR I was significantly (P < 0.05) reduced only in the BPI group. Leukocytopenia and granulocytopenia were significantly (P < 0.02) lessened in the BPI group, by an average of 59% leukocytopenia and 65% granulocytopenia, respectively. This study supports the concept of E. coli LPS neutralization by BPI in vivo and demonstrates that a moderate (70%) reduction in peak LPS-LAL activity is sufficient to alter some hematologic and cytokine manifestations of bacteremia. PMID- 8195316 TI - Endotoxin administration to humans primes alveolar macrophages for increased production of inflammatory mediators. AB - To elucidate potential mechanisms of the acute lung injury associated with endotoxemia, we evaluated the effect of intravenously administered endotoxin on the ability of alveolar macrophages isolated by bronchoalveolar lavage from normal subjects to produce inflammatory mediators. Within 1 hr of endotoxin (4 ng/kg body weight) administration, all 12 study subjects developed constitutional symptoms and leukopenia, and within 3 hr, low-grade fever. Resolution of symptoms and fever by 6 hr was accompanied by systemic granulocytosis. Although intravenously administered endotoxin appeared to activate a subset of circulating monocytes, it did not alter the bronchoalveolar lavage cell number, phenotype (95% macrophages), or constitutively expressed high levels of surface HLA-DR and O2-. In contrast, intravenous endotoxin primed the alveolar macrophages for enhanced lipopolysaccharide-induced secretion of interleukin-1 (11.8 to 25.8 U/ml; P = 0.04), tumor necrosis factor-alpha (titer, 6.8 to 13.6; P = 0.20), and prostaglandin E2 (38.4 to 116.3 ng/ml; P = 0.035). These results demonstrate that low-dose intravenous endotoxin primes human alveolar macrophages, which are already differentiated in situ, for enhanced secretion of inflammatory mediators. Such mediators may contribute to the pulmonary changes associated with endotoxemia and acute lung injury. PMID- 8195317 TI - Molecular and genetic basis of X-linked immunodeficiency disorders. AB - Within a short time interval the specific gene defects causing three X-linked human immunodeficiencies, agammaglobulinemia (XLA), hyper-IgM syndrome (HIGM), and severe combined immunodeficiency (XSCID), have been identified. These represent the first human disease phenotypes associated with each of three gene families already recognized to be important in lymphocyte development and signaling: XLA is caused by mutations of a B cell-specific intracellular tyrosine kinase; HIGM, by mutations in the TNF-related CD40 ligand, through which T cells deliver helper signals by direct contact with B cell CD40; and XSCID, by mutations in the gamma chain of the lymphocyte receptor for IL-2. Each patient mutation analyzed to date has been unique, representing both a challenge for genetic diagnosis and management and an important resource for dissecting molecular domains and understanding the physiologic function of the gene products. PMID- 8195319 TI - [Pathophysiology and operative timing of acute cholecystitis]. PMID- 8195318 TI - Anti-tetanus toxoid antibody production after mismatched T cell-depleted bone marrow transplantation. AB - We explored B-cell function after tetanus toxoid (TT) immunization in 12 children with severe combined immunodeficiency disease or leukemia who were long-term survivors of an HLA-matched sibling or haplocompatible T cell-depleted parental bone marrow transplant (BMT), 10 of their healthy donors, and 13 normal controls. Specific in vivo and in vitro anti-TT antibody (Ab) production were measured by ELISA. We studied donors' and recipients' peripheral blood mononuclear cells (PBMC) and mixed E- (non-T cells) and E+ cells (T cells) spontaneously and after stimulation by TT in the absence or presence of interleukin-2 (IL-2), IL-4, and IL-6. Five of the 12 patients and all donors and controls responded with in vivo anti-TT Ab. In vitro anti-TT Ab production correlated with the in vivo response. All seven of the nonresponders were either fully engrafted or mixed chimeras (donor T cells but autologous B cells and monocytes). We could not identify a T cell defect in four of the five nonresponders who were tested. In contrast, E- cells from three of three responders cooperated with fresh donor E+ cells even when they shared only one HLA haplotype. In three of seven nonresponders, in vitro anti-TT Ab production was restored after the addition of IL-4 or IL-6 but not IL-2. Our results suggest that the humoral immunodeficiency that exists post mismatched T cell-depleted BMT is either a B-cell, a monocyte, or a B-cell/T-cell cooperation defect which, in some patients, may be correctible with the addition of a cytokine. Also, it is not necessary to engraft donor B cells to achieve normal antibody responses and the ability to respond does not appear to correlate with pretransplant chemotherapy. PMID- 8195320 TI - [Modification of surface phenotype and function in intrahepatic lymphocytes during liver regeneration after partial hepatectomy]. AB - In the intrahepatic lymphocyte fraction (IHL) of mice whose livers have been perfused by Ca+2 and Mg+2 free Hank's balance salt solution, flow cytometric analysis reveals various cells similar to those found in the spleen (CD3+ cell, CD4+ cell, CD8+ cell, alpha beta TCR+ cell, gamma delta TCR+ cell, Thy1.2+ cell, B220+ cell and asialo-Gm1+ cell). The cytotoxic activity against YAC-1 cells in IHL is significantly higher than that in spleen cells. Furthermore, IHL has cytolytic activity against syngeneic thymoma BW5147 cells which is not found in spleen cells. Both cytotoxic activities of IHL are greatly weakened by the pretreatment of IHL with anti asialo-Gm1 Ab and rabbit complement. During liver regeneration after a partial hepatectomy, the percentages of lymphocyte subsets of IHL such as alpha beta TCR+ cells, gamma delta TCR+ cells and asialo-Gm1+ cells transiently increase 2 days after the partial hepatectomy and their cytotoxic activities against YAC-1 and BW5147 cells also reach a peak at that time. It is well known that the peak of mitotic index in regenerating parenchymal liver cells peaks 2 days after a partial hepatectomy and that the number of Pit cells peaks 10 to 14 days after. Compared with the time for reaching the highest mitotic index in regenerating parenchymal liver cells, the proliferation of Pit cells comes very late. It has not been clear which proliferation process in parenchymal liver cells is suppressed by activated Pit cells. Our findings in this paper reveal that the percentages and the cytotoxic activities of asialo Gm1+ cells in IHL reach their peak 2 days after an operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195321 TI - Growth control of primary culture hepatocytes by nonparenchymal liver cells. Role of interferon produced by liver sinusoidal cells. AB - Using the primary culture of liver cells, we showed that interferon produced by nonparenchymal liver cells inhibits the proliferation of cultured parenchymal liver cells. DNA synthesis of parenchymal liver cells was suppressed not only by their coculture with nonparenchymal liver cells but also by the addition of the culture supernatant of nonparenchymal liver cells. The suppressive activity of the supernatant correlated closely with the interferon (alpha + beta) level in the supernatant and was reduced by anti interferon (alpha + beta) serum. Furthermore, purified interferon (alpha + beta) also suppressed parenchymal liver cell proliferation in a dose-dependent manner and the suppression was released by anti interferon (alpha + beta) serum. The interferon level of the supernatant necessary for suppressing parenchymal liver cell proliferation, however, was extraordinarily low compared with purified interferon. The possibility exists that IFN in the culture supernatant of nonparenchymal liver cells works synergistically with other factors in the supernatant to suppress the cell proliferation. PMID- 8195322 TI - [Morphological characteristics of human mast cells in normal and pathological thyroid glands. Functional aspect of human mast cells in comparison with rat mast cells]. AB - We examined the distribution and population density of human mast cells in thyroid glands. The results were compared with those of Sprague-Dawley (SD) rats because they thyroid function of SD rats is known to be under the control of bioactive amines discharged from mast cells. Normal thyroid tissues were obtained either form autopsy or from a normal portion of the tissue distant from nodular lesions. Thyroid tissues were surgically removed from cases of Graves' disease and other tumorous lesions such as follicular adenoma, follicular carcinoma, papillary carcinoma and medullary carcinoma. The tissues were fixed with buffered formaldehyde or Carnoy fluid and embedded in paraffin. Mast cells were stained with toluidine blue and naphthol ASD chloroacetate esterase (esterase). Immunoperoxidase reactions to antihuman tryptase and chymase monoclonal antibodies were then observed. The mast cells were also observed by electron microscopy. The histamine content of the thyroid tissues was estimated by the high-performance liquid chromatography method. The mast cells in SD rat thyroid glands were scattered in perifollicular connective tissues which were comprised of capillaries, fibroblasts, nerve fibers and occasional fine deposits of collagen fibrils. Their cytoplasmic granules appeared to be distinct, electron dense and amorphous. In contrast, the mast cells in normal human thyroid glands were scattered exclusively over relatively thick interstitial spaces like the interlobular and subcapsular connective tissues. These mesenchymal tissues were composed of bundles of collagen fibrils, fibroblasts, histiocytes and thin cytoplasmic processes of unknown origin. In pathologic thyroid tissues, the mast cells were distributed in a similar pattern over the connective tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195323 TI - [Effects of intermittent cervical traction on muscle pain. Flowmetric and electromyographic studies of the cervical paraspinal muscles]. AB - The effects of cervical intermittent traction on neck and shoulder pain were evaluated in 96 patients. Namely, a 15-second traction of the neck was repeated with a 5-second interval between tractions. In 39 patients, blood flowmetry and electromyography were performed in the cervical paraspinal muscles before and after the traction treatment. The pain was relieved in 76 out of 96 cases (79.2%). The blood flow in the affected muscles was significantly decreased as compared with the controls. However, it showed a significant increase following the treatment in patients whose pain was relieved. The mean frequency of the initial myoelectric signals as observed with the surface electrode on the affected muscles was significantly lower than the controls. It increased however following the traction treatment in the case in which the pain was relieved. In conclusion, it may be stated that the cervical intermittent traction is effective in relieving pain, increasing the frequency of myoelectric signals and improving blood flow in affected muscles. PMID- 8195325 TI - [Renal transplantation. Experiences in the First Hospital of Nippon Medical School]. PMID- 8195324 TI - Amplification of N-myc gene and increase of urinary VMA and HVA in patients with neuroblastic tumors. AB - Neuroblastic tumor cases in our departments were evaluated in terms of the stage of the tumor, N-myc amplification, urinary vanillylamndelic acid (VMA)/homovanillic acid (HVA) and survival rate. Two asymptomatic cases, diagnosed when under a year old by mass screening, had no amplifications of N-myc but showed more than one value of urinary VMA/HVA ratio. The patients are now doing well eight years after complete excision of the neuroblastoma which had originated in the sympathetic ganglion. On the other hand, two other symptomatic cases, operated on at the ages of 3 and 5 years, showed remarkable amplifications with less than one value of urinary VMA/HVA, and died from the tumor soon after partial resection of the neuroblastoma and ganglioneuroblastoma which had originated in the adrenal gland and the sympathetic ganglion, respectively. The present monograph reports our cases and discusses prognostic factors. PMID- 8195326 TI - [Otitis media with effusion in children]. PMID- 8195327 TI - Splenic arterial portal infusion. PMID- 8195328 TI - The subclinical varicocele debate. AB - The debate concerning the indications to treat subclinical varicocele has been on going for 15 years. In order to understand this debate we have thoroughly reviewed the literature concerning the arguments for and against its treatment. Arguments posed by 59 investigators who considered the possibility of diagnosing subclinical varicocele were analysed. In 26 of these no definite statements were made concerning the value of treatment, in 29 there were positive statements and in only four were there negative statements. The arguments in favour of treatment were mainly based on positive results from patients and on the assumed lack of correlation between the size of varicocele and the degree of infertility. Although the majority of statements were positive, definite conclusions could not be drawn since data from a randomized prospective trial were not available. Consequently it is concluded that the subclinical varicocele debate can only be resolved by performing a randomized trial with treated and untreated groups of patients. Patients undergoing treatment for subclinical varicocele should be made aware that such treatment might not improve their fertility. PMID- 8195329 TI - Influence of the developmental stage and the equilibration time on the outcome of ultrarapid cryopreservation of mouse embryos. AB - Mouse embryos of different developmental stages from 1- to 8-cell inclusive were ultrarapidly frozen in 0.25 ml French straws after various periods of equilibration (1, 3, 5 and 9 min) in freezing-buffer containing 3.5 M dimethylsulphoxide (DMSO), 0.25 M sucrose, and 20% fetal calf serum (FCS) in phosphate buffered saline (PBS). After thawing in a 37 degrees C waterbath and dilution for 5 min in 0.25 M sucrose in PBS/FCS the embryos were cultured in Ham's F10 medium with 10% FCS (37 degrees C, 5% CO2, 95% humidity) for 4-6 days. The rates of expanded and hatching blastocysts were then evaluated and compared to the corresponding rates of non-frozen controls. Thus, for each cleavage stage, the optimal equilibration time was evaluated. It was 1 min for the 1-cell and 8 cell stages (32 and 81% blastocysts, respectively), and 3-5 min for the 2-cell (76 and 73%, respectively) and the 4-cell stage (88 and 87%, respectively). It is concluded that the ultrarapid freezing method described provides satisfactory results for all tested cleavage stages, but not for the 1-cell stage. PMID- 8195330 TI - The contribution of embryo cryopreservation to in-vitro fertilization/gamete intra-fallopian transfer: 8 years experience. AB - In this paper, the authors summarized their experience with embryo cryopreservation over an 8-year period. The results, therefore, reflect the long term benefit of embryo cryopreservation to the overall in-vitro fertilization/gamete intra-Fallopian transfer (IVF/GIFT) programme and to the women who had embryos cryopreserved. The stable survival rate of thawed embryos and pregnancy rate, especially over the past 4 years, suggests that the results can reliably be used to evaluate the efficacy of the embryo cryopreservation programme. The ongoing pregnancy rate of frozen/thawed embryo transfer is 10.9%, comparable with the ongoing pregnancy rate of fresh IVF/embryo transfer in our unit over the same period. In addition to those factors known to affect the pregnancy rate in fresh IVF/GIFT cycles, such as age of the recipients and number of embryos transferred, the major factor affecting the efficacy of the cryopreservation programme is the number of oocytes retrieved in the initial stimulation cycle, and the number of embryos available for cryopreservation. The storage time of cryopreserved embryos will also have a significant effect on the realization of the total potential of embryo cryopreservation. Overall the contribution of cryopreservation to our IVF/GIFT programme is substantial, increasing pregnancy rate by 4%, while the greater net benefit, of course, is for the women who had embryos cryopreserved (pregnancy rate increased by 7%), especially for those who returned for frozen/thawed embryo transfer cycles (pregnancy rate increased by 11%). PMID- 8195331 TI - Effect of sperm pre-treatments on the results of sub-zonal insemination (SUZI). AB - Follicular fluid and progesterone, which are present in the natural environment of oocytes, have been reported to induce the acrosome reaction and we compared their use in pretreatment of spermatozoa for human sub-zonal insemination (SUZI). Pre-treatment with follicular fluid (20% v/v) was associated with a higher fertilization rate than pre-incubation with progesterone (1 mmol/l) as assessed by both the embryos/injected oocytes rate (31.7 +/- 6.2% versus 13.5 +/- 5.9%, respectively; P < 0.01) and the male pronuclei/injected spermatozoon rate (10.5 +/- 3.3% versus 3.6 +/- 1.9%, respectively; P < 0.01). Since we have previously reported that pre-treatment with progesterone allowed a higher percentage of live reacted spermatozoa to be obtained, these results suggest that either progesterone induces modifications of the plasma membrane, which prevent fusion with the oolema, or that follicular fluid not only induces the acrosome reaction but increases the fusion ability by compounds other than progesterone. PMID- 8195332 TI - Manifestations of diabetes mellitus on mouse preimplantation development: effect of elevated concentration of metabolic intermediates. AB - The metabolic derangements of pregnancies complicated by diabetes mellitus, specifically hyperglycaemia and hyperketonaemia, are known to be teratogenic during the period of organogenesis in animals. We have shown previously that poorly controlled diabetes mellitus impairs in-vivo and in-vitro mouse preimplantation embryo growth, and that culturing embryos in elevated glucose concentrations only partially recreates this developmental delay. To extend this observation we examined the effect on mouse preimplantation embryo growth of elevated concentrations of other metabolic intermediates, which may be deranged in diabetes mellitus, namely lipids, lactate, glycerol, amino acids, and ketones. Two-cell embryos from ovulation-induced B6C3F1 mice were cultured for 72 h in the presence of added lipids (250 mg/dl), lactate (5 mM), glycerol (160 microM) or mixed amino acids (8.5% travasol, 7 mM) and showed no significant difference in growth over 72 h versus their control groups. However, growth of preimplantation embryos in acetoacetate (10 mM) or in the racemic mixture of DL-beta hydroxybutyrate (16 and 32 mM) revealed marked retardation versus controls when assessed either by distribution of developmental stages over time (24, 48, 72 h, P < 0.001) or by the difference in the average rank of sums indicating a delay in maturation (P < 0.0001). We conclude that elevated ketone concentrations adversely affect preimplantation embryo development. These findings extend previous studies which correlate uncontrolled diabetes mellitus as well as hyperglycaemia with abnormal organogenesis, and demonstrate that exposure to metabolic derangements may also hinder reproductive performance at even earlier stages in gestation. PMID- 8195333 TI - Assessment of functional integrity of frozen-thawed mouse embryos by albumin and leucine uptake. AB - To assess the effects of freezing-thawing on metabolic functions of embryos prior to implantation, we measured the uptake of [125I]bovine serum albumin (BSA) and [3H]leucine in 2-cell mouse embryos, that were freshly collected (control), exposed to cryoprotectants (non-frozen), and frozen-thawed, and in morulae and blastocysts cultured from these 2-cell embryos. No significant difference in [125I]BSA uptake by 2-cell embryos was observed among the three groups. However, [125I]BSA uptake by blastocysts in the frozen-thawed group was significantly reduced compared with the control and non-frozen groups. [3H]leucine uptake by 2 cell embryos in the frozen-thawed and non-frozen groups was significantly less than in the control group. Fluorescein diacetate staining was performed in the control and frozen-thawed 2-cell embryos. The intensity of fluorescence after fluorescein diacetate exposure did not differ between the control and frozen thawed embryos. The present study with mouse embryos suggests that freezing thawing procedures impair the metabolic functions, in particular the membrane transport system, of embryos. Measurements of BSA and leucine uptake in embryos may be useful for evaluating the quality of frozen-thawed embryos. PMID- 8195334 TI - Selection and micro-injection of acrosome-reacted human spermatozoa. AB - A method of selection of acrosome-reacted human spermatozoa is described. Petri dishes were coated with GB24 antibody, specific to the inner acrosomal membrane. The acrosome-reacted spermatozoa were fixed on the antibody and could be removed by aspiration with a micro-pipette. They were then injected into the perivitelline space of hamster eggs in order to check their fertilizing ability. This selection allowed the fertilization rate to be significantly increased (24 versus 7% for control spermatozoa; P < 0.01). This method could enhance the results of human sub-zonal insemination. PMID- 8195335 TI - A double-blind cross-over controlled study to evaluate the effect of human biosynthetic growth hormone on ovarian stimulation in previous poor responders to in-vitro fertilization. AB - The effect of exogenous human biosynthetic growth hormone (HGH; 12 IU/day; Norditropin, Novo-Nordisk) on the response to ovarian stimulation using a buserelin/human menopausal gonadotrophin (HMG) regimen was assessed in women who had previously shown a 'poor response' in spite of increasing doses of HMG. Forty patients were recruited into a prospective double-blind placebo-controlled study. The serum follicle stimulating hormone (FSH) on day 2-5 of a menstrual cycle (< 10 IU/l) was used to exclude any peri-menopausal candidates. The urinary 24 h GH secretion was normal in all patients. Thirty-three patients completed the study with 21 patients having human chorionic gonadotrophin (HCG) in both arms, thus providing a complete set of placebo control data. Of these 21 patients, the administration of HGH compared to the placebo cycle resulted in increased serum concentrations of fasting insulin on the 8th (median 3.9 versus 5.8 mU/l; P < 0.0005) and 13th (median 4.4 versus 5.8 mU/l; P < 0.05) day of HMG in those cycles receiving HGH. After 8 days of co-treatment with HGH the number of cohort follicles (14-16.9 mm) was significantly increased, but this change was not sustained on the day of HCG administration. No statistical difference in the serum oestradiol on the 8th day of HMG or day of HCG, length of the follicular phase, total dose of HMG used, or the number of oocytes collected was seen between the placebo or HGH cycles. This study demonstrates that HGH does not improve the ovarian response to ovulation induction in previous poor responders. PMID- 8195336 TI - Assessment of the developmental potential of frozen-thawed mouse oocytes. AB - Mouse oocytes were cryopreserved by a protocol shown previously to minimize damage to the zona pellucida and cytoskeletal system. After thawing, the incidence of fertilization did not differ from that in control groups of oocytes, and after fertilization, the ability of the fertilized frozen-thawed oocytes to develop to the blastocyst stage in vitro was only slightly less (77%) than that of the controls (87 and 89%). Transfer of frozen-thawed and fertilized oocytes after their culture to the blastocyst stage in vitro resulted in a lower implantation rate (46%) than for the controls (68-73%), but of the implanting embryos the same proportions in experimental and control groups survived to yield viable fetuses. In contrast, transfer after culture in vitro to the 2- to 4-cell stage resulted in similar implantation rates for control and frozen-thawed fertilized oocytes (70-84%), but the spontaneous abortion rate was higher for the embryos derived from frozen-thawed oocytes. Overall the cumulative survival rate for frozen oocytes transferred at the 2-cell stage (36%) was better than after transfer at the blastocyst stage (30%), but both were less than for the transfer at any stage of the control oocytes (47-55%). The cumulative survival of cryopreserved oocytes to viable fetuses was 30-40% less than that of the control oocytes. These results are compared with those from previous studies and the main remaining obstacles to completely successful cryopreservation are identified. PMID- 8195337 TI - Zona-opening of hamster oocytes: a comparative study using macro- and micro manipulation methods. AB - The present study compared a new macro-manipulation technique for zona-opening of hamster oocytes with existing micro-manipulation techniques. In experiment I the zona pellucida of hamster oocytes was partially opened with a 32 gauge steel needle (macro-manipulation) and these oocytes were then co-incubated with human spermatozoa at 36.5 degrees C in 5% CO2 in air for 3.5 h. Zona-free and zona intact oocytes similarly inseminated served as controls. Of 113 oocytes, 30 (26%) lysed following zona-opening with the macro technique. The sperm penetration rates of zona-opened and zona-free oocytes were 37% (31/83) and 60% (49/81) respectively (P < 0.01), with 12 and 28% oocytes respectively showing polyspermia (P < 0.05). No sperm penetration occurred in zona-intact oocytes. In experiment II the zona pellucida of hamster oocytes was partially opened by macro- or micro manipulation techniques before the oocytes were coincubated with human spermatozoa as in experiment I. Nine of 156 (6%) macro-manipulated and 11 of 133 (8%) micro-manipulated oocytes lysed following zona-opening. Of 147 remaining macro-manipulated and 122 remaining micro-manipulated oocytes, 80 (55%) and 79 (64%) respectively were penetrated (P > 0.05), with 30 and 37% respectively showing polyspermia (P > 0.05). These results demonstrate that macro-manipulation results in similar penetration and polyspermia rates as compared to conventional micro-manipulation. PMID- 8195338 TI - The obstetric outcome of singleton pregnancies following in-vitro fertilization/gamete intra-fallopian transfer. AB - The present study compares 465 singleton live deliveries from in-vitro fertilization/gamete intra-Fallopian transfer (IVF/GIFT) pregnancies with a large control population to evaluate the incidence of pre-term delivery and small for gestational age (SGA) or very small for gestation age (VSGA) babies resulting from IVF/GIFT pregnancies. Overall the incidence of SGA or VSGA from an IVF/GIFT pregnancy is higher than from the normal obstetric population (SGA odds ratio 1.76, 95% confidence interval (CI): 1.38-2.25 and VSGA odds ratio 1.61, 95% CI: 1.05-2.46) particularly among primiparous women (SGA odds ratio 1.99, 95% CI: 1.25-3.16 and VSGA odds ratio 1.97, 95% CI: 1.49-2.62). After stratifying by the cause of infertility, only women with unexplained infertility had a significantly higher proportion of SGA/VSGA babies. There was a significantly higher incidence of pre-term deliveries among the young primiparae (odds ratio 5.02, 95% CI: 3.09 8.13). Thus the excess risk of delivering a SGA/VSGA baby and pre-term delivery from an IVF/GIFT pregnancy seems to be largely confined to women with unexplained infertility and young primiparae. PMID- 8195339 TI - Serum CA 125 in a pregnancy generated by ovum donation. AB - Serum CA 125 was measured by radioimmunoassay during the first trimester at intervals of 2 weeks in a woman with Turner's syndrome, who conceived following ovum donation from a healthy anonymous donor. Serum CA 125 concentrations were lower than or at the 10th percentile of the normal range. These findings imply that CA 125 may be secreted from the ovary in the first trimester, or produced at another site in response to stimuli from the ovary. PMID- 8195340 TI - Parathyroid hormone related protein (PTHrP) gene expression in fetal and extra embryonic tissues of early pregnancy. AB - Parathyroid hormone related protein (PTHrP) is an important humoral factor in hypercalcaemia of malignancy. In addition there is increasing evidence that this peptide has a physiological role in fetal development, especially in cellular growth and differentiation. Both in-situ hybridization and immunohistochemistry were used together and for the first time to identify sites of PTHrP gene expression and peptide in fetal and extra-embryonic tissues of first trimester human pregnancy. PTHrP mRNA and peptide were identified in the avascular amnion and the syncytiotrophoblast while mRNA alone was expressed in the cytotrophoblast. Its expression in these extra-embryonic tissues is consistent with postulated roles for PTHrP in implantation, relaxation of endometrial muscle and regulation of vascular tone. Expression of both mRNA and peptide occurred in endo-, meso- and ectodermal structures of the fetus, consistent with local production of the peptide rather than cellular uptake from amniotic fluid and supporting a role for PTHrP in cellular growth and differentiation. PMID- 8195341 TI - Relationship between protein concentrations in embryological fluids and maternal serum and yolk sac size during human early pregnancy. AB - Coelomic fluid (n = 57), amniotic fluid (n = 61) and maternal serum (n = 81) were obtained from normal pregnancies between 7.7 and 13.9 weeks and assayed for total protein, alpha-fetoprotein (alpha FP), albumin and pre-albumin. The mean concentration of total protein in matched samples was 18 times higher in maternal serum than in the coelomic fluid and 54 times higher in the coelomic fluid than in amniotic fluid. The concentrations of total protein, albumin and pre-albumin decreased and that of alpha FP increased in maternal serum with advancing gestation. The yolk sac volume and the concentrations of total protein in the coelomic and amniotic fluids increased with gestational age. No difference was found for the crown-rump length, yolk sac volume and protein concentration in the coelomic fluid between two groups presenting with low and high maternal serum pre albumin concentrations. Before 11 weeks gestation, significant correlation was only found between yolk sac volume and coelomic fluid concentration of pre albumin as evaluated by both electrophoresis and immunonephelometry. These results suggest that during the first trimester of normal pregnancy, the placental metabolism and transfer rate of proteins is not directly influenced by the concentrations of protein in the maternal circulation and that the transfer of proteins through the amniotic membrane is limited. These results also indicate that during that period the secondary yolk sac may contribute to the protein content of the exocoelomic cavity, and that the embryo and its yolk sac and subsequently the fetus are the main source of the proteins present in the amniotic fluid. PMID- 8195343 TI - Personality characteristics analysis in couples undergoing artificial insemination. AB - The personality characteristics of 40 couples admitted into an artificial insemination scheme have been analysed. The personality study was carried out using Cattell's questionnaire 16 PF (form C) and EPI questionnaire (Eysenck Personality Inventory). The results show significant statistical differences between males and females with a greater conformity with the group, in women; women are also bolder and more disciplined from an emotional point of view, whereas men are more radical. PMID- 8195342 TI - Community attitudes to maternal age and pregnancy after assisted reproductive technology: too old at 50 years? AB - Community attitudes toward oocyte and embryo donation, and toward assisted reproduction after the menopause were assessed in this survey of 1131 Australians. Of the respondents, 64.2% believed that oocyte or embryo donation was an acceptable treatment for infertile couples, 54.6% felt that it was acceptable for a woman to have her own embryos transferred after the menopause, and 37.9% are accepting of the donation of eggs or embryos to post-menopausal women. There were no significant differences in response amongst different religious groups, or in relation to gender or income level. Significantly higher levels of acceptance were noted for all categories amongst those respondents aged < 35 years. Despite the established clinical ability to achieve pregnancy in the over 50 years age group, this survey reveals only minority community support for this practice. However, public opinion may alter in the future if the attitudes of the younger proportion of the sample are maintained. PMID- 8195344 TI - Psychological screening and the success of donor insemination. AB - In a previous case series, a psychologist's rating of couples' emotional adjustment and readiness for donor insemination was predictive of pregnancy rates. We attempted to replicate this finding with an extended series of 120 consecutive couples in which each spouse filled out questionnaires when evaluated for donor insemination. The Stress and Infertility Questionnaire measured specific attitudes and anxieties about donor insemination. The Brief Symptom Inventory assessed psychological distress. The Dyadic Adjustment Scale measured marital happiness. A psychologist used these questionnaires to rate the couple's overall adjustment in regard to donor insemination. Those couples rated as distressed had a session of psychological counselling. Outcome was reviewed at a mean of 20 months after evaluation, with categories of pregnancy, continuing donor insemination, failure to begin the programme, or dropped out. For the 120 couples overall, psychological factors did not predict pregnancy outcome. Younger age of the wife did predict higher pregnancy rates. PMID- 8195345 TI - Hypersecretion of luteinizing hormone (LH) and ovarian steroids in women with recurrent abortion. PMID- 8195346 TI - Exogenous steroids and the control of oestradiol secretion by human granulosa lutein cells by follicle stimulating hormone and insulin-like growth factor-I. AB - This study first examined the relative activities of 17 alpha-hydroxylase, 17,20 lyase and aromatase in human granulosa-lutein cells by challenging the cells with steroid precursors in the oestradiol biosynthetic pathway. When cells from four patients were challenged with precursor steroids on the pathway to oestrogen synthesis (pregnenolone, 17 alpha-hydroxypregnenolone, progesterone, 17 alpha hydroxyprogesterone and androstenedione at 5 x 10(-6) M), oestradiol (nmol/l) outputs after 1 day of culture were (median, interquartile range) as follows: 4.1 (2.1-8.8; pregnenolone), 3.1 (1.7-6.0; progesterone), 12.5 (6.9-18.1; 17 alpha hydroxypregnenolone), 8.2 (4.1-16.7; 17 alpha-hydroxyprogesterone) and 251 (140 819; androstenedione). No further increases were seen when the steroid concentration was increased to 1 x 10(-5) M. Basal oestradiol secretion was 3.5 (1.6-8.2) nmol/l. We conclude that the conversion of pregnenolone/progesterone to oestradiol by granulosa-lutein cells is rate limited by 17 alpha-hydroxylase activity but that these cells are capable of oestradiol secretion (in the nmol/l range) in the absence of androstenedione. In the second part of this study we examined the control of granulosa-lutein oestradiol secretion by follicle stimulating hormone (FSH) and insulin-like growth factor-I (IGF-I) in the presence and absence of exogenous androstenedione (10(-6) M). Cells were cultured for up to 6 days and basal oestradiol (nmol/l) fell dramatically over this period both in the presence and absence of androtenedione, e.g. from 339 (223-419) (median and interquartile range, cells from five patients cultured in the presence of androstenedion) after 2 days to 14 (7-59) after 6 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195347 TI - Effects of RU486 on the ovarian response of immature rats to pregnant mare's serum gonadotrophin or diethylstilbestrol. AB - The purpose of this study was to further investigate the role of progesterone in follicular development induced by pregnant mare serum gonadotrophin (PMSG) or diethylstilbestrol (DES), in pre-pubertal rats, using RU486 to prevent the receptor-mediated actions of progesterone. Intact or hypophysectomized 26-day-old rats received either a single injection of 10 IU PMSG i.p., or 2 mg DES s.c. daily for 3 days, with or without 0.8 mg RU486 s.c. daily for 3 days. Groups of rats were killed 51-96 h after the first injection. RU486 significantly increased the ovarian weight gain, the ovarian and circulating concentrations of progesterone, the concentrations of immunoreactive and bioactive LH and the number of ovulated oocytes in intact rats. RU486 did not affect the ovarian weight increase induced by PMSG or the ovulatory response following PMSG plus human chorionic gonadotrophin (HCG) in rats hypophysectomized 24 h before initiating treatment or in intact rats where ovulation was blocked with chlorpromazine. The ovarian weight gain, the development of antral follicles and the increments in tissue and plasma progesterone concentrations and luteinizing hormone (LH) plasma concentrations elicited by DES in intact rats, were further increased by concomitant treatment with RU486, whereas the ovarian weight increase and antral follicle development induced by DES were completely inhibited by RU486 in hypophysectomized rats. Follicles stimulated to grow by DES plus RU486, but not by DES alone, were capable of ovulating in response to HCG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195348 TI - Human endometrial maturation is markedly improved after luteal supplementation of gonadotrophin-releasing hormone analogue/human menopausal gonadotrophin stimulated cycles. AB - In human cycles stimulated for ovulation with gonadotrophin-releasing hormone (GnRH) agonists and human menopausal gonadotrophin (HMG), a luteal phase defect has been described. To evaluate the influence on the endometrium, endometrial development in GnRH agonist/HMG stimulated cycles was assessed in cycles with and without luteal phase supplementation. Endometrial histological maturation, ultrastructure and oestrogen receptor (ER) and progesterone receptor (PR) status were analysed in the mid-luteal phase. Serum concentrations of oestradiol and progesterone were measured daily from days 1-5 of the luteal phase. Supplementation of the luteal phase was achieved with either human chorionic gonadotrophin or natural progesterone, administered intramuscularly or intravaginally. In non-supplemented cycles all endometrial features were consistent with an impaired progesterone bioavailability. After supplementation of the luteal phase, fewer signs of luteal phase deficiency were visible, especially with the intravaginal route of progesterone administration. We concluded that the endometrial parameters confirm the need for luteal support in GnRH agonist/HMG stimulated cycles. PMID- 8195349 TI - Regulation of corpus luteum function. AB - The effects have been studied of different ovulation induction regimens [either clomiphene citrate or buserelin in combination with human menopausal gonadotrophin (HMG)] on the circulating concentrations of progesterone, oestradiol, relaxin and human chorionic gonadotrophin (HCG) during the first trimester of pregnancy. Ovulation induction with clomiphene resulted in elevated concentrations of gonadotrophins in both phases of the cycle, while during ovulation induction with buserelin, gonadotrophin concentrations were elevated in the follicular phase only. The concentrations of all corpus luteum products were greater in clomiphene pregnancies compared with spontaneous pregnancies, but only oestradiol and relaxin concentrations were greater in clomiphene pregnancies compared with buserelin pregnancies. The concentrations of HCG were significantly reduced in clomiphene pregnancies compared to natural pregnancies. Relaxin concentrations were significantly higher from 7 weeks gestation in buserelin compared with spontaneous pregnancies, while progesterone, oestradiol and HCG concentrations were not consistently different. Consistent associations were found between relaxin and HCG concentrations in spontaneous pregnancies and between the concentrations of relaxin and both progesterone and oestradiol in pregnancies achieved after ovulation induction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195350 TI - Sex steroids do not alter melatonin secretion in the human. AB - It is unclear whether sex steroids influence melatonin secretion in the human. In an attempt to find an answer to this important question 36 women within an age range of 19 to 40 years were studied within a 3-month period under the following conditions: natural menstrual cycle, ovulation induction with gonadotrophins, early pregnancy, and intake of monophasic or triphasic oral contraceptives. Except in the case of pregnancy, repeated measurements in the same individual were done because of the well-known large inter-individual variations in melatonin secretion. Melatonin concentration was measured in plasma samples obtained at 4-hourly intervals in a 24 h period and < 200 lux for all subjects studied. No consistent change in melatonin blood concentrations was demonstrated in response to the varying endogenous or exogenous concentrations of sex steroids. These observations suggest that circadian melatonin secretion is not significantly modulated by sex steroids. PMID- 8195351 TI - First established pregnancy and birth after induction of ovulation with recombinant human follicle-stimulating hormone in polycystic ovary syndrome. AB - This case report describes the first established pregnancy and birth after induction of ovulation with recombinant human follicle-stimulating hormone (FSH) in a woman suffering from chronic clomiphene-resistant anovulation due to polycystic ovary syndrome (elevated serum luteinizing hormone and testosterone concentrations together with polycystic ovaries). Starting on day 3 of a progestagen withdrawal bleeding, 75 IU of rFSH was administered i.m. daily until a single preovulatory follicle was seen upon transvaginal ultrasound examination at day 13. Ovulation was induced by a single i.m. administration of 10,000 IU of human chorionic gonadotrophin, after which a viable singleton pregnancy was revealed at a gestational age of 6 weeks. The course of pregnancy and labour was uneventful and no abnormalities were found upon a paediatric examination. PMID- 8195352 TI - Termination of early pregnancy with ZK 98,734: pharmacokinetic behaviour and clinical effect. AB - The antiprogestin RU 486 (mifepristone) is highly effective in inducing early abortion in women only if the compound is combined with a prostaglandin analogue. A new related antiprogestin, ZK 98,734, has been reported in animal studies to be much more potent as an abortifacient than mifepristone, concomitant with less antiglucocorticoid activity. The aim of the present two-centre study was to explore the abortifacient efficacy and plasma concentrations of ZK 98,734 in women seeking abortion. A total of 96 pregnant women with amenorrhoea of < 49 days were treated with oral doses of 12.5, 25, 50 or 100 mg ZK 98,734 twice daily for 4 days. The overall rate of complete abortion and continuing live pregnancies was 68 and 20% respectively, i.e. results comparable with treatment with mifepristone alone. No dose-response relationship was noted. In patients with complete abortion, signs of luteal dysfunction in terms of oestradiol and progesterone production were evident on the fourth treatment day, in contrast to patients with failures. Increased amounts of cortisol and prolactin were found during treatment both in successfully treated patients and failures, whereas aldosterone values remained unaffected. The effect on cortisol may indicate some antiglucocorticoid activity in the human. The concentrations of ZK 98,734 in peripheral blood after 25, 50 and 100 mg twice daily for 4 days were similar. The values were slightly above 0.5 mumol/l on the second day of treatment. Maximal concentrations of 0.7 mumol/l were seen on treatment day 4. Plasma concentrations of ZK 98,734 did not differ in cases of complete abortion and failures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195353 TI - Colour Doppler hysterosalpingosonography: a simple and potentially useful method to evaluate fallopian tubal patency. AB - The diagnostic efficacy of colour Doppler hysterosalpingosonography to evaluate Fallopian tubal patency was studied in 17 women. Of the 17 women, 12 were infertile and the remaining five were fertile and requested elective tubal ligation. Colour Doppler sonography was performed using the transabdominal approach 1-4 weeks after diagnostic laparoscopy during infertility work-up in the former, and 1-2 weeks after bilateral isthmic tubal ligation in the latter group. Sterile saline was used as the contrast agent. Laparoscopic chromopertubation was considered as the gold standard. The sensitivity and specificity of colour Doppler sonography were found to be 93 and 83%, respectively. A kappa value of 0.73 reflected good clinical agreement between the two techniques. Colour Doppler hysterosalpingosonography is concluded to be a relatively accurate and simple procedure to test tubal patency. The other advantages include absence of radiation and avoidance of potential allergic reactions to iodinated contrast agents employed for hysterosalpingography. However, the inability to delineate the inner architecture of the genital canal and to determine the exact location of tubal obstruction, when present, remain the disadvantages of this technique. PMID- 8195354 TI - Superovulation and timed intercourse: can it provide a reasonable alternative for those unable to afford assisted conception? AB - Superovulation was performed prospectively with pure follicle stimulating hormone (FSH) to a group of 224 infertile patients with ovulatory factor (51), male factor (60), mild/moderate endometriosis (24) and unexplained infertility (72). The aim was to produce three or four leading follicles in order to compensate for a 'deficient' factor. Ovulation was induced with human chorionic gonadotrophin (HCG) and monitoring was performed entirely by serial transvaginal ultrasound on alternate cycles up to a maximum of six cycles (1120 treatment cycles) with intervening cycles being used as self-controls (932 rest cycles). A further control group of 56 patients was matched for age, category and duration of infertility and was only scanned serially (336 control cycles). Seventy-four pregnancies were achieved and 54 delivered, giving a cumulative pregnancy rate per couple of 33% and a cumulative take home baby rate of 24% per couple after a maximum of six cycles of treatment. When compared with the rest or control cycles, treatment was significantly effective for ovulatory (P < 0.001), mild/moderate endometriosis (P < 0.01) and unexplained infertility (P < 0.01) but not for male infertility. Furthermore, pregnancy was five times more likely during the first four treatment cycles (P = 0.00006, odds ratio = 5) at the expense of a significant multiple pregnancy rate (18.9%) and mild/moderate ovarian hyperstimulation rate (12%). We conclude that four cycles of superovulation should be routinely offered to couples on waiting lists for assisted conception or to those unable to afford it, in anovulatory, mild/moderate endometriosis and unexplained infertility. These results need confirmation by a prospective multi-centre randomized study. PMID- 8195355 TI - Pentoxifylline potentiates ionophore (A23187) mediated acrosome reaction in human sperm: flow cytometric analysis using CD46 antibody. AB - The study was designed to investigate the effects of pentoxifylline on the acrosome reaction of human spermatozoa in vitro, and to determine whether the reaction is differently modulated after sperm selection by multiple tube swim-up and Percoll buoyant density centrifugation. The acrosome reaction was induced in vitro by using calcium ionophore (A23187) and was detected by measuring the fluorescence of FITC-conjugated goat anti-mouse immunoglobulin bound to CD46 antibody (which binds to the CD46 receptor site on the inner acrosomal membrane) by flow cytometry. Spermatozoa separated on Percoll displayed significantly lower spontaneous acrosome reactions (P = 0.002) than did those separated by the swim up technique. Pentoxifylline did not, by itself, induce acrosome reaction, but after induction with ionophore, it significantly increased the reaction (P = 0.003) and this increase was seen to be greater when Percoll separation was used as compared to the swim-up technique (P = 0.0002). We therefore conclude that Percoll selection of motile spermatozoa together with pentoxifylline treatment may be of value in assisted reproductive techniques, as an increased ARIC score arose after both treatments, and that flow cytometry allows a precise and rapid quantification of the acrosome reaction. PMID- 8195356 TI - Salpingectomy by operative laparoscopy and subsequent reproductive performance. AB - Between January 1984 and August 1991, 511 cases of extrauterine pregnancies were diagnosed by laparoscopy in our department. In 374 cases salpingectomy was performed: 184 by explorative laparotomy, and 190 by operative laparoscopy. Patients were scheduled for salpingectomy if one or more of the following criteria were fulfilled: (i) a ruptured tube which was surgically unsuitable for conservation; (ii) no interest in future fertility; (iii) tubes with ectopic gestation previously operated on; (iv) a previous tubal pregnancy on the same side, which was treated expectantly. Salpingectomy was performed via operative laparoscopy with bipolar diathermy forceps and laparoscopic scissors. Pregnancy rates, i.e. intra-uterine and repeat extra-uterine, were evaluated. The reproductive performance following salpingectomy did not differ significantly, whether by laparotomy or laparoscopy: the intra-uterine pregnancy rate was 78 and 64%, respectively and the repeat ectopic pregnancy rate was 12 and 6%, respectively. Salpingectomy via laparoscopy can be performed safely with a low incidence of complications, with subsequent reproductive performance comparable to laparotomy. PMID- 8195357 TI - Hysteroscopic incision of the septate uterus: scissors versus resectoscope. AB - Out of a total of 81 women who underwent hysteroscopic incision of symptomatic septate uteri during a 5-year period, 70 were analysed with respect to reproductive outcome. Division of the septum was performed with hysteroscopic scissors in 17 patients and by means of the resectoscope in 53. Pre-operative indications included infertility, repetitive pregnancy losses, abnormal uterine bleeding and intractable dysmenorrhoea. There were a total of 51 pregnancies after a mean period of 9.3 months following hysteroscopic metroplasty, of which 29 (56.8%) were carried to term, 12 (23.5%) were spontaneous abortions, and 10 (19.6%) are in progress. The post-treatment pregnancy success rate was 73%. The number of spontaneous abortions, pregnancies to term and mean time between surgery and conception was similar in both groups. There were three cases of perforation in the group of excision with hysteroscopic scissors and a case of pulmonary oedema in the group of the resectoscope. Although different advantages are provided by each technique, and more pregnancies were established using scissors, it seems that operator experience is a major consideration in performing these therapeutic hysteroscopic operations. PMID- 8195358 TI - Concentration of interleukin-1 beta correlates with prostaglandin E2 and F2 alpha in human pre-ovulatory follicular fluid. AB - To investigate the role(s) of interleukin-1 beta (IL-1 beta) in human ovarian function, we measured the concentrations of IL-1 beta, prostaglandins (PGs) and steroids in follicular fluid of 90 stimulated ovaries, with reference to oocyte maturation. Concentrations of IL-1 beta were significantly higher in the follicles from which mature oocytes were recovered than in follicles from which oocytes could not be recovered (P < 0.05). IL-1 beta concentrations also increased in association with oocyte maturation. Positive significant correlations were seen between IL-1 beta and prostaglandin E2 (PGE2) (r = 0.47, P < 0.001), and between IL-1 beta and prostaglandin F2 alpha (PGF2 alpha) (r = 0.22, P < 0.05) in pre-ovulatory follicular fluid, but not between IL-1 beta and oestradiol, or between IL-1 beta and progesterone. Follicular fluid IL-1 beta might contribute to prostaglandin-induced oocyte maturation and ovulation. PMID- 8195359 TI - Evaluation of the sites of ectopic pregnancies subsequent to reconstructive tubal surgery. AB - The sites of ectopic pregnancies in women who underwent various types of reconstructive tubal surgery were analysed and compared to the controls. Overall, ectopic pregnancies subsequent to all types of tubal surgeries were more often implanted proximally compared to the control population. PMID- 8195360 TI - Failure of laparoscopic treatment for peritoneal trophoblastic implants. AB - We report on two cases of peritoneal trophoblastic tissue implants, one after salpingostomy, and one after salpingectomy for ectopic pregnancy. During each secondary laparoscopy, simple excision of implants with laparoscopic biopsy forceps resulted in persistent elevated beta-human chorionic gonadotrophin (beta HCG) levels. Methotrexate therapy was used. Removal of all trophoblastic tissues present and avoidance of trophoblastic spillage during the laparoscopic procedure should prevent such an uncommon complication. PMID- 8195361 TI - Platelet activating factor enhances the acrosome reaction, fertilization in vitro by subzonal sperm injection and resulting embryonic development in the rabbit. AB - This study was conducted to investigate the effect of platelet activating factor (PAF) on the acrosome reaction and fertilizing capacity of spermatozoa, and development of the resulting embryos in the rabbit. Rabbit spermatozoa were exposed to PAF, lyso-PAF, or high ionic strength medium (HIS) prior to subzonal sperm injection (SUZI) into 326 mature oocytes, or morphological assessment of the acrosome reaction. The rates of fertilization and blastocyst formation were compared among the three treatment groups. Acrosome reaction was assessed by fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA) staining and electron microscopy. PAF-treated spermatozoa fertilized the oocytes at a significantly higher rate (56.1%) than did lyso-PAF-(36.8%, P < 0.01) or HIS (38.2%, P < 0.05) treated spermatozoa. The embryos produced by PAF-treated spermatozoa showed significantly higher blastocyst formation rates (34.0%) than lyso-PAF- (8.6%, P < 0.05) or HIS-(8.8%, P < 0.05) treated spermatozoa. FITC-PSA staining demonstrated a significantly higher incidence of acrosome reaction in PAF-treated spermatozoa (45.8%) than in lyso-PAF- (28.0%, P < 0.01) or HIS- (34.9%, P < 0.01) treated spermatozoa. Acrosome reaction of PAF-treated spermatozoa was also confirmed by electron microscopy. PAF treatment of spermatozoa enhances fertilizing capacity for SUZI possibly by augmenting the acrosome reaction. Enhanced embryonic development was also found in the oocytes fertilized by SUZI of PAF-treated spermatozoa. PMID- 8195362 TI - Characterization of Chlamydia pneumoniae species-specific proteins immunodominant in humans. AB - Proteins of Chlamydia pneumoniae immunodominant in humans were characterized with the sera of 13 patients who were not likely to have been exposed to C. trachomatis or C. psittaci. The serological responses among these patients were similar on a qualitative basis, but some differences were found quantitatively. However, the serological responses of the patients who were infected with C. pneumoniae differed markedly from those of two patients who were infected with C. trachomatis and two who were infected with C. psittaci and those of mice that were transtracheally infected with C. pneumoniae. Among proteins immunodominant in the patients who were infected with C. pneumoniae, a 40-kDa major outer membrane protein was genus specific and 53-, 46-, and 43-kDa proteins were species specific in their reactions with the majority of the human sera used. A few sera reacted strongly with a 73-kDa protein genus specifically. Some proteins with weak immunogenicity exhibited species specificity. An antigenic analysis with human sera and murine monoclonal antibodies against the 53-kDa protein showed that hte antigenicities were strictly conserved among the seven strains of C. pneumoniae tested. The genus-specific 73-kDa protein was solubilized with octylglucoside. All of the species-specific immunodominant proteins were solubilized with sodium dodecyl sulfate, but the genus-specific major outer membrane protein was not. These results suggest that a serological diagnosis of C. pneumoniae infection could be achieved species specifically by comparison of the serum responses to sodium dodecyl sulfate- and octylglucoside-soluble fractions. PMID- 8195363 TI - Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease. AB - Six patients from northern Minnesota and Wisconsin with a febrile illness accompanied by granulocytic cytoplasmic morulae suggestive of ehrlichial infection were identified. Two patients died, and splenic granulocytes of one patient contained cytoplasmic vacuoles with organisms ultrastructurally characteristic of ehrlichiae. From one patient, a 1.5-kb DNA product was amplified by PCR with universal eubacterial primers of 16S rDNA. Analysis of the nucleotide sequence of the amplified product revealed 99.9 and 99.8% similarities with E. phagocytophila and E. equi, respectively, neither of which has previously been known to infect humans. From the variable regions of the determined sequence, a forward primer specific for three organisms (human granulocytic ehrlichia, E. phagocytophila, and E. equi) and a reverse primer for these ehrlichiae and E. platys were designed. By nested PCR with amplification by the universal primers and then reamplification with the specific primers described above, the expected 919-bp product was generated from the blood of the index patient and three additional patients. Blood from these four patients and two more patients with granulocytic morulae contained DNA which was amplified by nested PCR involving a combination of a universal primer and the human granulocytic ehrlichia-E. phagocytophila-E. equi-E. platys group-specific primer. This apparently vector-borne human granulocytic ehrlichia has only 92.5% 16S rDNA homology with E. chaffeensis. Nested PCR with group-specific primers did not amplify E. chaffeensis DNA, and E. chaffeensis-specific primers did not amplify DNAs of the human granulocytic ehrlichia. Thus, six patients were shown to be infected by an Ehrlichia species never previously reported to infect humans. PMID- 8195364 TI - Arbitrarily primed PCR, ribotyping, and plasmid pattern analysis applied to investigation of a nosocomial outbreak due to Enterobacter cloacae in a neonatal intensive care unit. AB - In December 1992, Enterobacter cloacae was isolated from the oropharynx and respiratory tract of six ventilated neonates hospitalized in the intensive care unit (ICU) of our hospital. To establish the spread of the outbreak, 41 strains of E. cloacae were analyzed for genotypic markers by three methods: plasmid profile analysis, ribotyping with EcoRI or PvuII endonuclease, and arbitrarily primed (AP) PCR. The tested strains included 12 isolates from the 6 epidemic cases, 4 isolates from the respiratory tract of 4 children hospitalized in other wards during the same period, 13 isolates from 12 children hospitalized in pediatric units before or after the outbreak, and 12 epidemiologically unrelated isolates. Ribotyping and AP PCR demonstrated that each of the last 12 strains exhibited distinct genomic patterns, as did each of the strains isolated from neonates hospitalized before or after the epidemic peak. Conversely, two clones of strains were found among the isolates recovered in December, with concordant results being obtained by the three typing methods: the first clone included seven strains from five ventilated children in the ICU and two children from another ward; another clone was shared by one neonate in the ICU and an infant from another ward. These results indicate that ribotyping and AP PCR-the latter applied, to our knowledge, for the first time to the genotypic analysis of E. cloacae--represent very discriminatory tools for the investigation of nosocomial outbreaks caused by this species. PMID- 8195365 TI - Evaluation of a p21e-spiked western blot (immunoblot) in confirming human T-cell lymphotropic virus type I or II infection in volunteer blood donors. The Retrovirus Epidemiology Donor Study Group. AB - Current algorithms for the serologic confirmation of human T-cell lymphotropic virus type I and II (HTLV-I/II) antibody reactivity are complicated. We evaluated the performance of an HTLV-I Western blot (immunoblot) spiked with recombinant p21e protein (p21e WB) as an alternative to current confirmatory methods. These methods include the HTLV-I viral lysate Western blot and either a radioimmunoprecipitation assay or a p21e enzyme-linked immunosorbent assay. Five hundred fifty nine blood donations obtained from five U.S. blood centers and classified as HTLV-I/II seropositive (n = 149) or seroindeterminate (n = 410) by routine testing methods were further evaluated by PCR for proviral DNA and by the p21e WB. On the basis of serologic and PCR testing, 155 donations were classified as HTLV-I/II infected. The sensitivity of the p21e WB was 97.4%, slightly exceeding that of routine confirmatory testing. The specificity of the p21e WB was 97.5%, as determined by testing of 404 seroindeterminate samples that were negative in the PCR. The positive predictive value of the p21e WB was 94%. In contrast, the specificity and positive predictive value of routine confirmatory testing were both 100%. Follow-up sampling of presumptive p21e WB false-positive donors substantiated the absence of HTLV-I/II infection. Although the p21e WB used in this study has high sensitivity and may be useful as a confirmatory assay in epidemiologic research studies, it may not be ideal as a confirmatory test for the notification of blood donors. PMID- 8195366 TI - Detection of microsporidia by indirect immunofluorescence antibody test using polyclonal and monoclonal antibodies. AB - During a screening for monoclonal antibodies (MAbs) to the microsporidian Encephalitozoon hellem, three murine hybridoma cell lines producing strong enzyme linked immunosorbent assay (ELISA) reactivities were cloned twice, were designated C12, E9, and E11, and were found to secrete MAbs to the immunoglobulin M isotype. On subsequent ELISAs, the three MAbs reacted most strongly to E. hellem, and they reacted somewhat less to Encephalitozoon cuniculi and least to Nosema corneum, two other microsporidian species. The MAbs produced values of absorbance against microsporidia that were at least three times greater than reactivities obtained with control hybridoma supernatants or with uninfected host cell proteins used as antigens. By Western blot immunodetection, the three MAbs detected three E. hellem antigens with relative molecular weights (M(r)s) of 62, 60, and 52 when assayed at the highest supernatant dilutions producing reactivity. At lower dilutions, the MAbs detected additional proteins with M(r)s of 55 and 53. By using indirect immunofluorescence antibody staining, the MAbs, as well as hyperimmune polyclonal murine antisera raised against E. cuniculi and E. hellem, were able to detect formalin-fixed, tissue culture-derived E. cuniculi and E. hellem and two other human microsporidia, Enterocytozoon bieneusi and Septata intestinalis, in formalin-fixed stool and urine, respectively. E. bieneusi, however, stained more intensely with the polyclonal antisera than with the MAbs. Neither the MAbs nor the hyperimmune murine polyclonal antibodies detected Cryptosporidium, Giardia, Trichomonas, or Isospora spp. At higher concentrations, the polyclonal antisera did stain N. corneum and yeast cells. The background staining could be absorbed with Candida albicans. These results demonstrate that polyclonal antisera to E. cuniculi and E. hellem, as well as MAbs raised against E. hellem, can be used for indirect immunofluorescence antibody staining to detect several species of microsporidia known to cause opportunistic infections in AIDS patients. PMID- 8195367 TI - Comparison of phenotypic methods and DNA hybridization for detection of methicillin-resistant Staphylococcus aureus. AB - One hundred thirty-eight Staphylococcus aureus isolates from patients with severe staphylococcal infections were collected in 15 French hospitals. Detection of the mec gene was performed by dot blot hybridization with a specific DNA probe. Dot blot results were used to characterize the isolates as methicillin susceptible (77 isolates) or resistant (61 isolates). The isolates were screened for methicillin resistance by an agar spread method on Mueller-Hinton plates containing oxacillin (2 and 10 micrograms/ml) and were incubated at 37 degrees C, with 10(8) CFU as the inoculum. MICs of oxacillin and methicillin were determined by the agar dilution method on Mueller-Hinton plates without NaCl, by using 10(5) CFU per spot, after 24 and 48h of incubation at 30 or 37 degrees C. Moderately elevated MICs were found for 20 isolates (14.5%). The mec gene was detected in six (30%) of the isolates expressing a low level of resistance to methicillin and/or oxacillin. As determined by comparison with probe hybridization results, the spread plate method with oxacillin at 2 micrograms/ml was more sensitive (sensitivity, 100%) and specific (specificity, 100%) than agar dilution with either methicillin or oxacillin in identifying methicillin resistance or susceptibility. Determinations of methicillin and oxacillin MICs by the agar dilution method had a specificity of 99 to 100% depending on the conditions of incubation, but the sensitivity was below 85% whatever the duration or temperature of incubation. PMID- 8195368 TI - Ability of canine Lyme disease vaccine to protect hamsters against infection with several isolates of Borrelia burgdorferi. AB - We used flow cytometry to determine levels of borreliacidal antibodies in hamsters after vaccination with a commercially available canine Lyme disease vaccine. In addition, we evaluated the ability of vaccinated hamsters to resist infection with several isolates of Borrelia burgdorferi. Borreliacidal antibodies could be detected 1 week after a primary vaccination, peaked at weeks 3 to 5, and then rapidly declined. One week after a booster vaccination, borreliacidal activity was detected at a dilution of 1:10,240, and it decreased fourfold by week 10 after the booster vaccination. Vaccinated hamsters were protected against infection with < or = 10(6) B. burgdorferi 297 organisms during the peak borreliacidal response (5 weeks after primary vaccination or 2 weeks after booster vaccination). However, hamsters were not fully protected from development of Lyme arthritis when the titer of borreliacidal antibodies was < 1:5,120. In addition, no significant borreliacidal activity was induced against B. burgdorferi C-1-11, LV4, or BV1, which belong to three other seroprotective groups. These studies demonstrate that vaccination with the canine Lyme disease vaccine induces protective antibodies against B. burgdorferi 297. However, significant levels of borreliacidal antibodies are not produced until 5 weeks after vaccination, and protection is short-lived. In addition, no borreliacidal activity was induced against other isolates of B. burgdorferi. Because of this, the incorporation of multiple isolates or protein subunits may be necessary to increase the effectiveness of future vaccines. PMID- 8195369 TI - Use of PCR-enzyme immunoassay for identification of influenza A virus matrix RNA in clinical samples negative for cultivable virus. AB - Influenza A virus infections are a major cause of morbidity and mortality worldwide. Standard diagnostic methods either are not efficient in identifying infected individuals in a timely manner or lack sensitivity. We developed a PCR enzyme immunoassay (PCR-EIA) for the detection of influenza A virus RNA in respiratory secretions. A reverse transcription PCR was performed with oligonucleotide primers directed at a highly conserved area of the influenza A matrix gene. Amplified DNA was identified by hybridization in solution to a nested biotinylated RNA probe and quantitated in an EIA. PCR-EIA detected small quantities of RNA from the three prevalent subtypes of human influenza A virus. Influenza B and C, parainfluenza, measles, mumps, and respiratory syncytial viruses tested negative. The potential efficiency of PCR-EIA for use in clinical diagnosis was determined by testing 90 nasal wash specimens obtained daily over a 10-day period from nine human volunteers infected with influenza A virus. Thirty seven of the postinfection samples had detectable influenza A virus RNA by PCR EIA, whereas only 26 postinfection samples were positive by culture. PCR-EIA was particularly efficient for the identification of influenza A virus in samples obtained more than 4 days after infection. Seventeen of 45 such samples were positive, whereas virus was cultivated from 4 samples (P < 0.00005). All preinfection samples from volunteers subsequently infected with influenza A virus were negative by PCR-EIA, as were samples from a volunteer infected with parainfluenza virus type 3. Nucleic acid amplification techniques represent important tools for the timely and sensitive diagnosis of influenza A virus infections and, therefore, their management and control. PMID- 8195370 TI - Analysis of western blotting (immunoblotting) technique in diagnosis of congenital syphilis. AB - The diagnosis of congenital syphilis in apparently healthy infants continues to be problematic. Immunoglobulin M antibodies specific for a subset of Treponema pallidum antigens have been detected by Western blotting (immunoblotting). In the present study we investigated the sensitivity and specificity of this method. We tested 26 infants aged 0 to 4 months who fulfilled the accepted criteria for the diagnosis of congenital syphilis. There were 14 symptomatic infants. Sera from 13 of these infants were positive for the 47-kDa treponemal antigen (92% sensitivity). The remaining 12 infants were clinically asymptomatic when tested at birth but subsequently displayed features consistent with the disease. Reactive blots (antibodies to the 47- and/or the 15-kDa antigens) were noted in 10 of the 12 infants (83% sensitivity). Thirty infants whose mothers had syphilis were monitored and shown to be uninfected. Nonreactive blots were seen in sera from 27 infants, while sera from 3 older infants had false-positive tests (90% specificity). The Western blotting technique is sensitive (even in the diagnosis of clinically inapparent cases) and, in the absence of immunoglobulin M rheumatoid factor, is a useful confirmatory test for congenital syphilis. PMID- 8195371 TI - Plague pandemics investigated by ribotyping of Yersinia pestis strains. AB - Yersinia pestis is the causative agent of plague, a disease which has caused the deaths of millions of people and which persists now in endemic foci. The rRNA gene restriction patterns (i.e., ribotypes) of 70 strains of Y. pestis, isolated on the five continents over a period of 72 years, were determined by hybridization with a 16S-23S rRNA probe from Escherichia coli. The combination of the EcoRI and EcoRV patterns resulted in the elucidation of 16 ribotypes. Two of them (B and O) characterized 65.7% of the strains studied, while the 14 other ribotypes were found in no more than three strains each. A relationship was established between biovars and ribotypes: strains of biovar Orientalis were of ribotypes A to G, those of biovar Antiqua were of ribotypes F to O, and those of biovar Medievalis were of ribotypes O and P. Great heterogeneity in rRNA restriction patterns was found among strains isolated in Africa; this heterogeneity was less pronounced among Asian isolates and was completely absent from the American strains. Pulsed-field gel electrophoresis was performed on the DNAs of some strains, but it appeared that different colonies from the same strain displayed different pulsed-field gel electrophoresis patterns and therefore that this technique was not suitable for comparison of Y. pestis isolates. In contrast, the ribotypes of individual colonies within a given strain were stable and were not modified after five passages in vivo. A clear correlation between the history of the three plague pandemics and the ribotypes of the strains could be established. PMID- 8195372 TI - Application of PCR to detect Norwalk virus in fecal specimens from outbreaks of gastroenteritis. AB - Norwalk virus (NV) and other small round-structured viruses (SRSVs) are frequent causes of gastroenteritis outbreaks. The recent cloning and sequencing of the NV genome has made it possible to detect NV and Norwalk-related viruses from fecal specimens by reverse transcription (RT)-PCR. We applied this technique to the examination of a total of 139 fecal specimens from 19 outbreaks characterized by NV serology, including 56 samples from 7 NV outbreaks, 36 from 6 Norwalk-related virus outbreaks, and 47 from 6 outbreaks with SRSVs visualized by electron microscopy that were serologically unrelated to NV. Three primer pairs were evaluated: two pairs in the polymerase region of NV and one pair near the 3' end of the genome. When one set of primers (primer pair 51-3) from the polymerase region was used, 40% of all samples were positive by RT-PCR and specimens from the NV outbreaks were more likely to be positive (64%) than those from outbreaks associated with Norwalk-related viruses (44%) or SRSVs (8%). To determine the relationship of the outbreak strains to NV, we compared the sequences of a 145 base portion of the polymerase gene from 10 specimens obtained from five different outbreaks characterized as NV by serology. No two outbreak strains had the same sequence in this 145-base portion of the polymerase gene, and the identities of the nucleotide and amino acid sequences of these products compared with the sequences of the corresponding region of NV ranged from 62 to 79% and 69 to 90%, respectively. Because of sequence diversity in the polymerase region, the successful application of RT-PCR to investigations of outbreaks of suspected NV associated gastroenteritis will depend on the use of either multiple primer pairs or primers made against regions of the genome that are more conserved. PMID- 8195373 TI - Evaluation of Staf-Sistem 18-R for identification of staphylococcal clinical isolates to the species level. AB - The accuracy and efficiency of Staf-Sistem 18-R (Liofilchem s.r.l., Roseto degli Abruzzi, Teramo, Italy) were compared with those of conventional biochemical methods to identify 523 strains belonging to 16 different human Staphylococcus species. Overall, 491 strains (93.9%) were correctly identified (percentage of identification, > or = 90.0), with 28 (5.4%) requiring supplementary tests for complete identification. For 14 isolates (2.8%), the strains did not correspond to any key in the codebook and could not be identified by the manufacturer's computer service. Only 18 isolates (3.4%) were misidentified. The system is simple to use, is easy to handle, gives highly reproducible results, and is inexpensive. With the inclusion of more discriminating tests and adjustment in supplementary code numbers for some species, such as Staphylococcus lugdunensis and Staphylococcus schleiferi, Staf-Sistem 18-R is a suitable alternative for identification of human coagulase-positive and coagulase-negative Staphylococcus species in microbiological laboratories. PMID- 8195374 TI - Inhibitory effect of the Isolator blood culture system on growth of Mycobacterium avium-M. intracellulare in BACTEC 12B bottles. AB - The examination of 6,938 clinical specimens collected during the period January 1991 through December 1992 suggested that the Isolator blood culture system (Wampole) inhibited growth of Mycobacterium avium-M. intracellulare complex (MAC) in BACTEC 12B medium. Of 162 MAC blood culture isolates, 94% were recovered from Lowenstein-Jensen (LJ) medium, while only 50% were recovered from 12B medium. The time to detection with LJ medium was 18 days, while that with 12B medium was 24 days. In contrast, 62% of the 305 MAC nonblood culture isolates were recovered from the LJ medium, while 87% were found in the 12B medium. The time to detection for these cultures was also reversed, i.e., 28 days for LJ medium versus 15 days for 12B medium. Dilution studies using the lysis-anticoagulant reagent from Isolator tubes demonstrated inhibition of both clinical and American Type Culture Collection strains of MAC, even at low concentrations of lysis-anticoagulant reagent. Washing the Isolator blood sediment prior to inoculating the 12B bottles eliminated any growth inhibition. Clinical and experimental data suggest that the use of the Isolator blood culture tube with the BACTEC 12B medium is contraindicated for mycobacterial blood cultures. PMID- 8195375 TI - Detection of equine arteritis virus following amplification of structural and nonstructural viral genes by reverse transcription-PCR. AB - A reverse transcription (RT)-PCR assay was developed for the detection of equine arteritis virus (EAV) in cell culture supernatant and in horse semen. Four different sets of oligonucleotide primers complementary to sequences located in the 3' end of the polymerase gene (open reading frame [ORF] 1b) and to sequences representing the entire ORFs 3, 4, and 7, which encode for nonstructural (ORFs 3 and 4) or viral nucleocapsid (ORF 7) proteins, were compared for their abilities to amplify the targeted EAV sequences by the RT-PCR procedure. The sensitivities of the RT-PCR for amplification of EAV sequences located in the 3' end of ORF 1b and ORF 4 were 2 median tissue culture infective doses (TCID50s) of viral particles in the EAV-infected cell culture supernatant for both ORFs and 20 and 200 TCID50s of viral particles, respectively, in virus-containing horse semen. The sensitivities were much lower when primers complementary to ORFs 3 and 7 were used in the RT-PCR, with a minimum detection limit of only 2 x 10(4) TCID50s of viral particles in virally infected cell culture supernatant, as determined by analyzing the resulting RT-PCR products on ethidium bromide-stained agarose gels. The specificities of the RT-PCR assays for all primer sets tested were confirmed when the amplified cDNA products of the expected size reacted positively with the corresponding virus-specific digoxigenin-labeled cDNA probes in the chemiluminescence assays. Although the sensitivity of the RT-PCR for amplification of ORF 3 and 7 sequences was lower, all sets or primers were capable of amplifying several cell culture-adapted EAV field isolates when the virus was present in high enough quanities in the test sample. When horse semen samples were analyzed for the presence of EAV by the RT-PCR with primers specific to the ORF 1b 3' end and ORF 4 sequences and by virus isolation in cell cultures, there was 100% concordance among the assays. The RT-PCR assay targeting the 3' end of ORF 1b and/or ORF 4 EAV RNA may be an alternative to conventional methods for the diagnosis of EAV infection in horses. PMID- 8195376 TI - Pseudomonas aeruginosa serotype O12 outbreak studied by arbitrary primer PCR. AB - A total of 16 colonizing and infecting ofloxacin-resistant Pseudomonas aeruginosa strains and two strains isolated from ventilation equipment fluids, all with similar colonial morphologies and with minor but distinct susceptibility differences, were suspected of belonging to a single outbreak and were studied by arbitrary primer (AP) PCR. Thirteen nonrelated strains were included to evaluate the discriminatory capacity of the technique. AP PCR fingerprinting was compared with serotyping, phage typing, and antibiotic susceptibility testing. AP PCR was performed independently with three different primers. The different AP PCR typing systems yielded almost identical patterns for the epidemic strains and enabled us to differentiate most of the nonrelated strains from each other and from the outbreak strains. The combination of AP PCR typing and the phenotyping techniques that we used enabled us to conclude that an outbreak was occurring. In general, the typeability of AP PCR was greater than those of phage typing and serotyping, while the discriminatory powers of the three methods were comparable. PMID- 8195377 TI - A more reliable PCR for detection of Mycobacterium tuberculosis in clinical samples. AB - Diagnostic techniques based on PCR have two major problems: false-positive reactions due to contamination with DNA fragments from previous PCRs (amplicons) and false-negative reactions caused by inhibitors that interfere with the PCR. We have improved our previously reported PCR based on the amplification of a fragment of the Mycobacterium tuberculosis complex-specific insertion element IS6110 with respect to both problems. False-positive reactions caused by amplicon contamination were prevented by the use of uracil-N-glycosylase and dUTP instead of dTTP. We selected a new set of primers outside the region spanned by the formerly used primers to avoid false-positive reactions caused by dTTP-containing amplicons still present in the laboratory. With this new primer set, 16 copies of the IS6110 insertion element, the equivalent of two bacteria, could be amplified 10(10) times in 40 cycles, resulting in a mean efficiency of 77% per cycle. To detect the presence of inhibitors of the Taq polymerase, which may cause false negative reactions, part of each sample was spiked with M. tuberculosis DNA. The DNA purification method using guanidinium thiocyanate and diatoms effectively removed most or all inhibitors of the PCR. However, this was not suitable for blood samples, for which we developed a proteinase K treatment followed by phenol chloroform extraction. This method permitted detection of 20 M. tuberculosis bacteria per ml of whole blood. Various laboratory procedures were introduced to reduce failure or inhibition of PCR and avoid DNA cross contamination. We have tested 218 different clinical specimens obtained from patients suspected of having tuberculosis. The samples included sputum (n=145), tissue biopsy samples (n=25), cerebrospinal fluid (n=15), blood (n=14), pleural fluid (n=9), feces, (n=7), fluid from fistulae (n=2), and pus from a wound (n=1). The results obtained by PCR were consistent with those obtained with culture, which is the "gold standard." We demonstrate that PCR is a useful technique for the rapid diagnosis of tuberculosis at various sites. PMID- 8195378 TI - Detection of Bacteroides fragilis in clinical specimens by PCR. AB - The direct detection of Bacteroides fragilis from clinical specimens was examined by using the PCR method for amplifying a specific fragment of the glutamine synthetase gene from B. fragilis. By this method, all five B. fragilis strains tested were detected, but DNAs from anaerobic bacteria of 24 other species tested, from aerobic bacteria of 12 species tested, and from human leukocytes were not amplified. Using the nested PCR method, we were able to detect as little as one bacterial cell or 100 fg of chromosomal DNA of B. fragilis. A total of 39 clinical specimens, which consisted of 19 bronchial aspirates, 10 percutaneous lung aspirates, 2 transtracheal aspirates, 6 pleural fluid specimens, and 2 pus specimens, were tested. All four culture-positive samples, of which two were bronchial aspirates, one was pleural fluid, and one was pus, were positive by PCR. Among 35 culture-negative samples, 2 bronchial aspirates were positive by PCR. One was from a patient whose two previous samples were positive by both culture and PCR. It had been submitted for culture several hours after collection, and clindamycin had been administered to the patient before collection of the specimen. The other bronchial aspirate positive by PCR was from a pneumonia patient who had also been administered clindamycin. We believe that B. fragilis was present in these two specimens but that either it was dead, it was below the level detectable by culture, or the process of anaerobic culture was unsuccessful. Thus, the PCR method may be considered useful for the sensitive and rapid detection of anaerobes in clinical specimens. PMID- 8195379 TI - Molecular epidemiology of nosocomial invasive aspergillosis. AB - Moderately repeated DNA sequences were used to fingerprint strains of Aspergillus fumigatus isolated from patients with invasive aspergillosis and their hospital environment. Most strains sampled from the environment displayed different Southern blot hybridization patterns. A temporal survey of air contaminants showed that some strains can persist in the same environment for at least 6 months. Patients with invasive aspergillosis were infected by a single strain. In two patients, a nosocomial origin of infection was suggested. PMID- 8195380 TI - Detection of Klebsiella pneumoniae and Escherichia coli strains producing extended-spectrum beta-lactamases. AB - Plasmids encoding extended-spectrum beta-lactamases of the TEM, SHV, and AmpC families were introduced into common Escherichia coli and Klebsiella pneumoniae hosts to create a homogeneous panel for evaluating the abilities of five test systems to detect resistance to eight beta-lactam antibiotics. Although MICs, as determined by agar dilution or E test strips, were increased and disk diffusion zone diameters were diminished, breakpoints for resistance were often not reached, and neither approach was sensitive in detecting resistance to oxyimino beta-lactams. The MicroScan 18-h microdilution or Vitek rapid automated procedures were similarly insensitive. Ceftazidime was the best single test antibiotic for detecting extended-spectrum beta-lactamase production. beta Lactamases TEM-7 and TEM-12 were particularly difficult to detect. Because of such difficulties, the prevalence of extended-spectrum beta-lactamases is likely to be greater than is currently appreciated. PMID- 8195381 TI - Detection of African horse sickness virus by reverse transcription-PCR. AB - Reverse transcription-PCR (RT-PCR) was used to detect African horse sickness virus (AHSV). A single primer pair which amplified a 423-bp fragment of the S8 gene which encodes the NS2 protein of AHSV was identified. Amplification of this fragment from all nine serotypes of AHSV was achieved with these primers. Between 10(1) and 10(2) copies of AHSV genomic double-stranded RNA could be detected by RT-PCR followed by agarose gel electrophoresis and ethidium bromide staining. Application of RT-PCR to blood samples from AHSV-infected horses resulted in earlier detection of viremia than virus isolation did. Furthermore, viremia was detected by RT-PCR in blood samples from horses infected with an avirulent isolate of AHSV which were negative by virus isolation. AHSV was also detected by RT-PCR in spleen and lung samples from horses which died of AHSV infection. These results indicate that RT-PCR is a rapid and sensitive method for the identification of horses infected with AHSV. PMID- 8195382 TI - Enzyme electrophoresis, sero- and subtyping, and outer membrane protein characterization of two Neisseria meningitidis strains involved in laboratory acquired infections. AB - Two cases of laboratory-acquired infections due to Neisseria meningitidis were suspected to have occurred in two French hospitals. The first case occurred shortly, i.e., 3 days, after one strain had been handled by a laboratory technician, and the link between this strain and the strain causing meningitis was easily established. In the second case, infection occurred 3 weeks after 10 strains had been handled by a technician. In this case, it was necessary to use high-resolution markers in order to establish the link between the infecting strain and 1 of the 10 strains handled. The antigenic formulae of the two infecting strains (serogroup:serotype:subtype) were, respectively, C:NT:P1.12 and B:2a:P1.2. Outer membrane protein profile analysis and multilocus enzyme electrophoresis unequivocally confirmed the identity of the respective strains. PMID- 8195383 TI - Detection and nucleotide sequence analysis of the speC gene in Swedish clinical group A streptococcal isolates. AB - The production of pyrogenic exotoxins SpeA, SpeB, and SpeC by group A streptococci has been associated with streptococcal toxic shock syndrome. Several epidemiological studies using DNA hybridization and PCR analysis have been performed in attempts to correlate one or several of the toxins with streptococcal toxic shock syndrome. The results reveal great variation in the occurrence of the speA and speC genes among clinical isolates. In this study, we show that the speC gene could be detected by nested PCR in five Swedish T1M1 strains isolated from patients infected with group A streptococci as well as in three Norwegian T1M1 isolates, previously reported to lack speC as determined by dot blot hybridization. To verify the identities of the amplified products, the nucleotide sequences of the PCR fragments from one Swedish T1M1 strain and from the toxin reference strain NY5 were determined. The nucleotide sequences showed that the amplified products were speC and of allele type C2, on the basis of the nucleotides in positions 438 and 456. However, one additional base pair substitution was found in NY5 at position 147 and in the Swedish isolate at position 157, which resulted in nonsynonymous amino acid changes. Thus, these speC genes represent two new allelic variants. PMID- 8195384 TI - Isolation of Borrelia burgdorferi from biopsy specimens taken from healthy looking skin of patients with Lyme borreliosis. AB - Erythematous skin lesions due to infection with Borrelia burgdorferi will often disappear without antibiotic treatment. The aim of the study was to assess whether after disappearance of the erythematous skin lesion B. burgdorferi is still present in the healthy-looking skin of untreated patients. In six patients, a skin biopsy specimen was taken at the site of a previous erythematous skin lesion 1 to 6 months after disappearance of the lesion. Four of them presented with early disseminated Lyme borreliosis. In one additional patient with early disseminated Lyme borreliosis, the site of a previous tick bite was biopsied. None of these patients had been treated with antibiotics before presentation. The cultures of the skin biopsy specimens of the seven patients showed growth of Borrelia species. By rRNA gene restriction analysis and genospecies-specific PCR, six isolates were classified as Borrelia garinii and one as Borrelia group VS461. These results show that B. burgdorferi can still be cultured from the skin after disappearance of the erythematous skin lesion or at the site of a previous tick bite. PMID- 8195385 TI - A 4-year survey of antimicrobial susceptibility trends for isolates from cattle with bovine respiratory disease in North America. AB - The antimicrobial susceptibility trends of bovine respiratory disease (BRD) pathogens isolated from 1988 to 1992 were determined. A total of 880 isolates representing Pasteurella haemolytica, Pasteurella multocida, and Haemophilus somnus were used in the study. Overall, resistance to ampicillin, tetracycline, erythromycin, and sulfamethazine was frequently encountered among strains of P. haemolytica and P. multocida. Ceftiofur, an extended-spectrum cephalosporin originally marketed in 1988 for the treatment of BRD, was very active against the BRD pathogens tested; the MIC of ceftiofur for 90% of isolates tested was < or = 0.06 microgram/ml. Resistance to spectinomycin varied on the basis of the breakpoint used. Substantial variation in the year-to-year susceptibility of BRD pathogens to tilmicosin, a new macrolide antimicrobial agent, was observed. The proportion of susceptible P. haemolytica isolates ranged from 84.7% in the second year to 7.1% in the third year and 78.2% in the fourth year. Similar fluctuations were observed with strains of P. multocida. PMID- 8195386 TI - Dilution assay statistics. AB - A parametric method of statistical analysis for dilution assays is developed in detail from first principles of probability and statistics. The method is based on a simple product binomial model for the experiment and produces an estimate for the concentration of target entities, a confidence interval for this concentration, and an indicator of the quality of the assay called the p value for goodness of fit. The procedure is illustrated with data from a virologic quantitative micrococulture assay used to quantify free human immunodeficiency virus in clinical trials. The merits of the procedure versus those of nonparametric methods of estimating the dilution inducing a 50% response rate are discussed. Advantages of the proposed approach include plausibility of the underlying assumptions, ability to assess plausibility of specific experimental outcomes through their likelihood, and plausibility of confidence intervals. PMID- 8195387 TI - Rapid identification of mycolic acid patterns of mycobacteria by high-performance liquid chromatography using pattern recognition software and a Mycobacterium library. AB - Current methods for identifying mycobacteria by high-performance liquid chromatography (HPLC) require a visual assessment of the generated chromatographic data, which often involves time-consuming hand calculations and the use of flow charts. Our laboratory has developed a personal computer-based file containing patterns of mycolic acids detected in 45 species of Mycobacterium, including both slowly and rapidly growing species, as well as Tsukamurella paurometabolum and members of the genera Corynebacterium, Nocardia, Rhodococcus, and Gordona. The library was designed to be used in conjunction with a commercially available pattern recognition software package, Pirouette (Infometrix, Seattle, Wash.). Pirouette uses the K-nearest neighbor algorithm, a similarity-based classification method, to categorize unknown samples on the basis of their multivariate proximities to samples of a preassigned category. Multivariate proximity is calculated from peak height data, while peak heights are named by retention time matching. The system was tested for accuracy by using 24 species of Mycobacterium. Of the 1,333 strains evaluated, > or = 97% were correctly identified. Identification of M. tuberculosis (n = 649) was 99.85% accurate, and identification of the M. avium complex (n = 211) was > or = 98% accurate; > or = 95% of strains of both double-cluster and single-cluster M. gordonae (n = 47) were correctly identified. This system provides a rapid, highly reliable assessment of HPLC-generated chromatographic data for the identification of mycobacteria. PMID- 8195388 TI - Comparison of PCR with direct examination of bone marrow aspiration, myeloculture, and serology for diagnosis of visceral Leishmaniasis in immunocompromised patients. AB - A PCR assay amplifying a repeated sequence from the Leishmania infantum genome was compared with direct examination of bone marrow aspirate, myeloculture, and serology for the diagnosis of visceral leishmaniasis in immunocompromised patients. Of 73 patients living in an area endemic for leishmaniasis and where visceral leishmaniasis was suspected by physicians, only 10 had an indisputable diagnosis of visceral leishmaniasis. None of the diagnostic tests performed in the study achieved 100% sensitivity for diagnosing visceral leishmaniasis. PCR exhibited superior sensitivity (82%) in comparison with bone marrow aspirate examination (55%) and myeloculture (55%). Our PCR assay also showed good specificity (97%), negative predictive value (97%), and positive predictive value (82%) even when all unconfirmed PCR results were scored as false positives. Serology exhibited good sensitivity (80%) and excellent specificity (100%), negative predictive value (98%), and positive predictive value (100%) in diagnosing new cases of visceral leishmaniasis but failed to diagnose relapses. We also observed consistent negative serological results using several different immunological detection methods for 2 of the 10 patients with confirmed cases of visceral leishmaniasis. This lack of serological reactivity persisted throughout the course of their infections. These results demonstrate the importance of using PCR as an aid in the diagnosis of visceral leishmaniasis in immunocompromised patients. PMID- 8195389 TI - Effect of simultaneous administration of cold-adapted and wild-type influenza A viruses on experimental wild-type influenza infection in humans. AB - On the basis of the ability of the attenuated cold-adapted strain of influenza A virus to suppress disease production in ferrets simultaneously infected with epidemic influenza virus (P. Whitaker-Dowling, H.F. Maassab, and J.S. Youngner, J. Infect. Dis. 164:1200-1202, 1991), an evaluation of the ability of the cold adapted virus to modify clinical disease in humans was made. Adult volunteers with prechallenge serum hemagglutination-inhibition titers to the influenza A/Kawasaki/86 (H1N1) virus of < or = 1:8 received either 10(7) 50% tissue culture infective doses of the wild-type A/Kawasaki virus or a mixture of 10(7) 50% tissue culture infective doses of each of the wild-type virus and a cold-adapted A/Kawasaki reassortant virus by intranasal drops in a randomized, double-blind fashion. Symptoms and wild-type virus shedding were assessed daily for 6 days following challenge. Results were compared with those derived from another group of volunteers who received only cold-adapted virus. Volunteers who received the mixed inoculum of cold-adapted and wild-type viruses had lower symptom scores than those who received wild-type virus alone, suggesting that coinfection with the cold-adapted virus may modify wild-type virus infection, but the differences were not statistically significant in this small study. The data demonstrate that administration of cold-adapted influenza A virus to humans at the time of wild type virus infection is a safe procedure. PMID- 8195390 TI - Isolation of Borrelia burgdorferi from saliva of the tick vector, Ixodes scapularis. AB - A method for cultivating and isolating Lyme disease spirochetes, Borrelia burgdorferi, from the saliva of vector ticks, Ixodes scapularis (formerly known as Ixodes dammini), is described. Saliva was collected from partially engorged ticks after application of pilocarpine to induce salivation. B. burgdorferi was isolated from 8 of 14 (57%) of the saliva samples derived from ticks infected with the bacteria, as determined by direct immunofluorescent-antibody assay of tick hemolymph. A comparison of the protein profiles of the salivary isolates and a highly passaged strain (B31) showed that the salivary isolates all lacked a 22 kDa protein known to increase with continuous passage, but exhibited larger amounts of the OspA and OspB proteins than did the highly passaged B31 strain. PMID- 8195391 TI - Investigation of an outbreak of Clostridium difficile infection in a general hospital by numerical analysis of protein patterns by sodium dodecyl sulfate polyacrylamide gel electrophoresis. AB - One hundred forty-five cultures of Clostridium difficile, including strains from an apparent nosocomial outbreak of infection, were characterized by one dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole cell proteins. Each protein pattern was characterized by the presence of one to three dense bands which were highly reproducible. The first 100 strains (in chronological order) were used as the basis for a numerical analysis which divided the strains into 17 phenons (EP types 1 to 17). The protein patterns of the remaining 45 strains were identified to type by comparing their individual patterns against a data base made up of the protein patterns of the first 100 strains. EP type 1 was the most common, with 70 of 139 (50%) patient isolates having this pattern type, and it accounted for 26 of 35 strains (74%) from patients in a medical teaching ward from which the outbreak was believed to have originated. This type was also found as a high proportion of isolations in a number of other medical and oncology wards, but the majority of these isolates occurred subsequent to the isolations on the initial outbreak ward. This technique can therefore provide a method for tracing the possible spread of epidemic strains in hospitals and other institutions and may contribute to a better understanding of the epidemiology of C. difficile. PMID- 8195392 TI - Evaluation of enzyme immunoassay for Candida cytoplasmic antigens in neutropenic cancer patients. AB - A Candida albicans cytoplasmic antigen enzyme immunoassay (CACP antigen EIA) was developed with antibodies raised against antigens prepared from yeast cells grown under standardized growth conditions. The C. albicans components reactive in the EIA were shown to be predominantly proteins with associated carbohydrates. Denaturing gel electrophoresis revealed the presence of five major CACP proteins with molecular weights between 36,000 and 44,000. The clinical usefulness of the CACP EIA was evaluated by retrospective blinded measurement of 89 serum samples from 31 granulocytopenic patient episodes. Twice-weekly surveillance cultures, sequential serum samples (approximately once per week or with change of the clinical course), and standard diagnostic criteria of fungal infection were used to categorize patients. The sensitivity and specificity of the CACP assay on the basis of serum samples were 82 and 100%, respectively (67 and 100% on the basis of patient episodes). The positive and negative predictive values were 100 and 97% for serum (100 and 93% for patient episodes). By comparison, the CANDTEC assay had low sensitivity (33%) and poor positive predictive values (50%). The CACP EIA may be a useful test suitable for further evaluations as a method for the diagnosis of invasive Candida infection in neutropenic cancer patients. PMID- 8195393 TI - Detection of Borrelia burgdorferi in urine of Peromyscus leucopus by inhibition enzyme-linked immunosorbent assay. AB - An inhibition enzyme-linked immunosorbent assay was developed to detect Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, in urine from white-footed mice (Peromyscus leucopus). Of the 87 urine specimens tested from 87 mice collected in widely separated tick-infested sites in Connecticut, 57 (65.5%) contained detectable concentrations of spirochetal antigens. Forty-seven (62.7%) of 75 serum samples analyzed contained antibodies to B. burgdorferi. In culture work with tissues from bladders, kidneys, spleens, or ears, 50 of 87 mice (57.5%) were infected with B. burgdorferi. Thirty-eight (76%) of 50 infected mice had antigens of this spirochete in urine, while 36 (72%) individuals had infected bladders. Of those with infected bladders, 24 (66.7%) mice excreted subunits or whole cells of B. burgdorferi into urine. Successful culturing of B. burgdorferi from mouse tissues, the presence of serum antibodies to this bacterium, and detection of antigens to this spirochete in urine provide further evidence that multiple assays can be performed to verify the presence of B. burgdorferi in P. leucopus. PMID- 8195395 TI - Bisulfite or sulfite inhibits growth of Helicobacter pylori. AB - Bisulfite or sulfite was found to be inhibitory to Helicobacter pylori growth. A modified version of Brucella broth (BB), bisulfite-less BB (BLBB), supported rapid, robust, and consistent growth of H. pylori. We suggest that BLBB simply be called "Pylori broth" for distinction from Brucella broth. PMID- 8195394 TI - Identification of Bordetella pertussis infection by shared-primer PCR. AB - A shared-primer PCR method for the detection of infection was developed by using primers derived from DNA sequences upstream of the structural genes for the porin proteins of Bordetella pertussis and Bordetella parapertussis. This method resulted in a 159-bp PCR product specific for B. pertussis and a 121-bp DNA fragment specific for B. parapertussis and allowed for the simultaneous detection of these pathogens. The PCR procedure was shown to be very specific since no PCR product was obtained from 36 non-Bordetella bacterial DNAs. Nasopharyngeal aspirates (NPAs) from children suspected of having pertussis were evaluated by the PCR method, culture, and the Chinese hamster ovary (CHO) cell assay, which detects pertussis toxin. B. pertussis was cultured from 119 of 205 NPAs assayed, and the presence of pertussis toxin was detected in 69 of the NPAs by the CHO cell assay. When ethidium bromide staining was used to detect PCR products, 100 NPAs gave positive results by shared-primer PCR; 94 of these NPAs were also positive by culture. The result indicated a sensitivity of 79% for PCR when culture was used as the standard. The sensitivity of PCR was increased to 95% when a digoxigenin immunoblot system was used. An additional 20 NPAs from patients with suspected pertussis that were culture negative also gave positive results by PCR. The specific and sensitive PCR method described here should be useful for both the clinical diagnosis of pertussis and case identification in vaccine trials. PMID- 8195396 TI - Antimicrobial susceptibility of Staphylococcus hyicus isolated from exudative epidermitis in pigs. AB - Exudative epidermitis or greasy pig syndrome is caused by the coagulase-variable staphylococcal species Staphylococcus hyicus. Treatment of this disease is problematic because of the limited number of antimicrobial agents available for this purpose. Thirteen antimicrobial agents were evaluated for their activities against 100 S. hyicus strains isolated from pigs with exudative epidermitis. Novobiocin was the most active compound tested, with an MIC for 90% of the strains tested (MIC90) of < or = 0.06 microgram/ml. Enrofloxacin, ampicillin, and ceftiofur were the next most active compounds, with MIC90s of 0.25, 0.5, and 1.0 microgram/ml, respectively. However, 41.4% of the 99 strains tested were positive for beta-lactamase production. The MIC90s of erythromycin, tetracycline, and streptomycin were > 32.0 micrograms/ml. Initial testing with sulfadiazine trimethoprim yielded an MIC90 of > 64.0 micrograms/ml, but subsequent testing with thymidine phosphorylase-supplemented medium yielded an MIC90 of 0.06 microgram/ml. Both lincomycin and spectinomycin were relatively inactive against the S. hyicus strains tested, with MIC90s of > 64.0 and > 128.0 micrograms/ml, respectively. However, the combination of the two compounds at ratios of 1:2 (lincomycin to spectinomycin) and 1:8 were more active, with MIC90s of 16.0 and 4.0 micrograms/ml, respectively. These results indicate that novobiocin and sulfadiazine-trimethoprim were the most active compounds tested against the S. hyicus strains isolated from pigs with exudative epidermitis. Furthermore, the combination of lincomycin and spectinomycin was more active than the individual compounds against the strains tested. PMID- 8195397 TI - Detection of bacteremia by Difco ESP blood culture system. AB - In a multicenter study, the Difco ESP blood culture system (Difco Laboratories, Detroit, Mich.) was compared with the BACTEC NR660 system (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.). The ESP system monitors each blood culture bottle every 12 to 24 min to detect changes in oxygen consumption and gas production by microbes. Equal volumes of blood were inoculated into aerobic ESP 80A and BACTEC 6A, 16A, or PEDS Plus broths and anaerobic ESP-80N and BACTEC 7A or 17A broths and were incubated for up to 7 days. ESP bottles contain supplemented tryptic soy broth without antimicrobial agent-adsorbing resins. From 7,532 aerobic compliant sets, the ESP system detected 356 clinically significant positive cultures and the BACTEC NR660 system detected 329. From 6,007 anaerobic cultures, the ESP system detected 234 clinically significant positive cultures and the BACTEC NR660 system detected 198. In aerobic broths, 292 organisms were isolated from both systems and 78 organisms were isolated from the ESP system alone, whereas 54 organisms were isolated from the BACTEC NR660 system alone (P < 0.05). Among individual organisms, pneumococci were isolated significantly more often in ESP aerobic broths. In anaerobic broths, 180 organisms were isolated from both systems and 68 organisms were isolated from the ESP system alone, whereas 35 organisms were isolated from the BACTEC NR660 system alone (P < 0.05). Aerobic gram-positive organisms as a group and Candida spp. were isolated significantly more often in ESP anaerobic broths. Both systems detected 207 clinically significant bacteremic episodes and the ESP system alone detected 63, whereas the BACTEC NR660 system alone detected 32 (P < 0.05). Significantly more episodes of bacteremia caused by Staphylococcus epidermidis and anaerobes were detected by the ESP system. The differences in the numbers of organisms detected >6h earlier in ESP broths compared with BACTNEC NR660 broths were significant, as were earlier times to detection. Although the total number of organisms detected was not significantly different, the ESP system alone detected more organisms in a shorter time than did the BACTEC NR660 system alone. The continuous monitoring capability of the ESP system makes it an attractive alternative to the BACTEC NR660 system. PMID- 8195398 TI - Escherichia coli O157:H7 generates a unique biochemical profile on MicroScan conventional gram-negative identification panels. AB - More than 90% of the strains of Escherichia coli O157:H7 that were identified on a MicroScan gram-negative dried conventional (overnight) panel gave one of two unique biochemical profile numbers that were not detected in other d-sorbitol negative E. coli or in other strains isolated from pathogenic processes. This suggests that the panel has the capability of being used as a preliminary screening tool for O157:H7 strains involved in hemorrhagic colitis when MacConkey sorbitol agar is not available. PMID- 8195399 TI - Evaluation of an automated immunodiagnostic assay, VIDAS Rotavirus, for detection of rotavirus in fecal specimens. AB - Four hundred sixty-four fecal specimens were tested for rotavirus by three immunoassays, VIDAS Rotavirus (bioMerieux Vitek, Hazelwood, Mo.), Rotaclone (Cambridge Biotech Corporation, Worcester, Mass.), and Pathfinder Rotavirus (Sansfi Diagnostics Pasteur, Chaska, Minn.). Twenty-seven discordant specimens were evaluated by electron microscopy. The sensitivities, specificities, positive predictive values, and negative predictive values were 98, 99.3, 98.7, and 99%, respectively, for VIDAS Rotavirus; 100, 99, 98.1, and 100%, respectively, for Rotaclone; and 100, 92.4, 87.3, and 100%, respectively for Pathfinder Rotavirus. PMID- 8195400 TI - Bias of culture techniques for diagnosing mixed Mycobacterium genavense and Mycobacterium avium infection in AIDS. AB - Disseminated Mycobacterium avium infection is a common complication in late-stage AIDS. We describe a patient seropositive for human immunodeficiency virus with a disseminated infection caused by mycobacteria. Acid-fast rods were visible by microscopy in stool and bone marrow and in specimens from skin, liver, spleen, lung, and lymph nodes. Using molecular biology techniques and standard culture techniques, we found evidence of a mixed mycobacterial infection with M. genavense and M. avium. We suggest that the prevalence of M. genavense infection in patients with AIDS is underestimated because of the bias toward M. avium when using standard techniques for the detection and identification of mycobacteria. PMID- 8195401 TI - Factors influencing detection of quantitative cytomegalovirus antigenemia. AB - Of 20 blood specimens testing positive for cytomegalovirus antigen after immediate processing, 19 (95%) remained positive when kept at room temperature for 24 h before processing. Quantitative antigenemia decreased by an average of 44% after storage. Compared with acetone fixation, formaldehyde fixation showed improved readability, fewer artifacts, and a higher degree of sensitivity. PMID- 8195402 TI - Comparative virulence of blood and stool isolates of Shigella sonnei. AB - Shigellemia is rare in developed countries and might result from the emergence of unusually virulent strains. We compared systemic invasiveness markers of isolates from the blood of 3 temporally clustered patients with Shigella sonnei bacteremia in Boston with those of 11 unrelated contemporaneous strains from stools of people in New England. We found no difference between the two groups in O-chain length by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, mouse 50% lethal dose, in vivo response to iron, and susceptibility to serum, which varied from moderately susceptible to ultrasusceptible. Mean intraperitoneal 50% lethal doses of smooth form I colonies for mice were equally low (10(5.8) CFU) in both groups, and the 50% lethal doses were lowered equally further in the two groups by predosing with iron to levels useful in mouse model sepsis studies. S. sonnei bacteremia may reflect compromised host defenses, not bacterial virulence. PMID- 8195404 TI - Utility of paired blood cultures and smears in diagnosis of disseminated Mycobacterium avium complex infections in AIDS patients. AB - For 273 patients evaluated for disseminated Mycobacterium avium complex infection, a total of 1,047 mycobacterial blood cultures (MBCs) were submitted; the M. avium complex was recovered from 140 (13%) of the specimens. Results for the paired MBCs were highly concordant: in 392 of 462 (85%) culture sets, both MBCs were negative, in 53 of 462 (11%) sets, both MBCs were positive, and in only 17 of 462 (4%) sets was one culture positive and the other negative. Acid-fast smears were done on sediments from 671 specimens; smears were positive for 4 of 98 (4%) cultures that grew the M. avium complex. A single MBC should be obtained and then repeated if negative and disseminated M. avium complex infection is still clinically suspected. Use of direct acid-fast smears of sediments is not a reliable means of detecting mycobacteremia. PMID- 8195403 TI - Interference of immunoglobulin G (IgG) antibodies in IgA antibody determinations of Chlamydia pneumoniae by microimmunofluorescence test. AB - In the microimmunofluorescence test for measuring immunoglobulin A (IgA) antibodies against Chlamydia pneumoniae, removal of interfering IgG antibodies made IgA antibody reactivity patterns in 952 serum samples easier to interpret, prozone effects disappeared, and titers increased, especially in the sera with high IgG titers. IgA rheumatoid factors did not interfere in the assay. PMID- 8195405 TI - Cokeromyces recurvatus, a mucoraceous zygomycete rarely isolated in clinical laboratories. AB - Cokeromyces recurvatus Poitras was isolated from an endocervical specimen obtained from a 37-year-old, insulin-dependent diabetic. The patient's diabetic condition had been well controlled for 10 years, and she had no other known medical problem. This is only the fourth time that this zygomycete has been recovered from a human source. While there was no evidence of tissue invasion in the present patient, the observation of fungus-like structures in two separate Papanicolaou-stained cervical smears prepared 1 year apart suggests that C. recurvatus may be capable of colonizing endocervical tissue. PMID- 8195406 TI - Discrimination of epidemic and nonepidemic methicillin-resistant Staphylococcus aureus strains on the basis of protein A gene polymorphism. AB - The X region of the protein A gene of Staphylococcus aureus contains a highly polymorphic sequence which is composed of repeats of 24 bp. We used amplification by PCR to investigate whether this region could be used to discriminate between epidemic and nonepidemic methicillin-resistant S. aureus (MRSA) strains. Most epidemic MRSA strains (24 of 33) harbored more than seven repeats, while most nonepidemic MRSA strains (10 of 14) contained seven or fewer repeats. It is conceivable that a longer X region results in a better exposition of the Fc binding region of protein A, thereby facilitating colonization of host surfaces and contributing to the epidemic phenotype. PMID- 8195407 TI - Potential use of BacT/Alert automated blood culture system for antifungal susceptibility testing. AB - A simple, rapid susceptibility test is needed to determine the possible resistance of yeasts to commonly used antifungal agents. The BacT/Alert automated blood culture system was evaluated as one technology for development of such a test. Yeast nitrogen base was used as the growth medium, and amphotericin B was the test antifungal agent. Isolates of various Candida species, Torulopsis glabrata, Saccharomyces cerevisiae, and Cryptococcus neoformans were evaluated. The results suggest that detection of amphotericin B resistance of yeast isolates within 12 to 14 h after inoculation of test medium is possible. PMID- 8195408 TI - Enzyme-linked immunosorbent assay-enzyme-linked coagulation assay for detection of antibodies to Clostridium botulinum neurotoxins A, B, and E and solution-phase complexes. AB - The solution-phase complex assay for toxins A, B, and E from Clostridium botulinum (Elcatech, Inc., Winston-Salem, N.C.) was modified to measure antibody. The addition of unlabeled polyclonal antibodies to a mixture consisting of toxin with chicken antibody and RVV-XA-labeled horse antibody reduces the sensitivity of detection of neurotoxin. This reduction in sensitivity can be used as a measure of the specific antibody titer. PMID- 8195409 TI - Rapid detection of Vibrio cholerae O1 in stools of Peruvian cholera patients by using monoclonal immunodiagnostic kits. Loyaza Cholera Working Group in Peru. AB - We compared stool culture with two commercial Vibrio cholerae O1 rapid diagnostic kits which detect antigen in 100 adults with cholera in Peru. Serum vibriocidal antibody titer was used as an external reference. Both rapid diagnostic kits appeared to detect cholera more frequently than did culture and were highly specific. PMID- 8195410 TI - Identification of a clone of Escherichia coli O103:H2 as potential agent of hemolytic-uremic syndrome in France. PMID- 8195411 TI - Standard specification for transferring digital neurophysiological data between independent computer systems (ASTM E1467-92) PMID- 8195412 TI - American Electroencephalographic Society Guidelines in Electroencephalography, Evoked Potentials, and Polysomnography. PMID- 8195413 TI - Guideline three: minimum technical standards for EEG recording in suspected cerebral death. American Electroencephalographic Society. PMID- 8195414 TI - Guideline thirteen: guidelines for standard electrode position nomenclature. American Electroencephalographic Society. PMID- 8195415 TI - Guideline fourteen: guidelines for recording clinical EEG on digital media. American Electroencephalographic Society. PMID- 8195416 TI - Guideline fifteen: guidelines for polygraphic assessment of sleep-related disorders (polysomnography). American Electroencephalographic Society. PMID- 8195417 TI - Guideline sixteen: policies and guidelines for clinical neurophysiology laboratory accreditation. American Electroencephalographic Society. PMID- 8195418 TI - Report of the Committee on Infectious Diseases. PMID- 8195419 TI - Syllabus for clinical electroencephalographers. PMID- 8195420 TI - Guideline four: standards of practice in clinical electroencephalography. American Electroencephalographic Society. PMID- 8195421 TI - Guideline five: recommendations for writing job descriptions for technologists and samples. American Electroencephalographic Society. PMID- 8195422 TI - Guideline one: minimum technical requirements for performing clinical electroencephalography. American Electroencephalographic Society. PMID- 8195423 TI - Guideline six: recommendations for telephone transmission of EEGs. American Electroencephalographic Society. PMID- 8195424 TI - Guideline seven: a proposal for standard montages to be used in clinical EEG. American Electroencephalographic Society. PMID- 8195425 TI - Guideline eight: guidelines for writing EEG reports. American Electroencephalographic Society. PMID- 8195426 TI - Guideline nine: guidelines on evoked potentials. American Electroencephalographic Society. PMID- 8195427 TI - Guideline two: minimum technical standards for pediatric electroencephalography. American Electroencephalographic Society. PMID- 8195428 TI - Guideline ten: guidelines for writing clinical evoked potential reports. American Electroencephalographic Society. PMID- 8195429 TI - Guideline eleven: guidelines for intraoperative monitoring of sensory evoked potentials. American Electroencephalographic Society. PMID- 8195430 TI - Guideline twelve: guidelines for long-term monitoring for epilepsy. American Electroencephalographic Society. PMID- 8195431 TI - Academic achievement and psychological adjustment in short children. The National Cooperative Growth Study. AB - Limited information is available on the educational and behavioral functioning of short children. Through 27 participating medical centers, we administered a battery of psychologic tests to 166 children referred for growth hormone (GH) treatment (5 to 16 years) who were below the third percentile for height (mean height = -2.7 SD). The sample consisted of 86 children with isolated growth hormone deficiency (GHD) and 80 children with idiopathic short stature (ISS). Despite average intelligence, absence of significant family dysfunction, and advantaged social background, a large number of children had academic underachievement. Both groups showed significant discrepancy (p < .01) between IQ and achievement scores in reading (6%), spelling (10%), and arithmetic (13%) and a higher-than-expected rate of behavior problems (GHD, 12%, p < .0001; ISS, 10%, p < .0001). Behavior problems included elevated rates of internalizing behavior (e.g., anxiety, somatic complaints) and externalizing behavior (e.g., impulsive, distractable, attention-seeking). Social competence was reduced in school-related activities for GHD patients (6%, p < .03). The high frequency of underachievement, behavior problems, and reduced social competency in these children suggests that short stature itself may predispose them to some of their difficulties. Alternately, parents of short, underachieving children may be more likely to seek help. In addition, some problems may be caused by factors related to specific diagnoses. PMID- 8195432 TI - Parental anxiety and minor illness. AB - Anxious parents can present a challenge to pediatricians. This study examines the relationship of the anxiety of parents seeking pediatric care for minor conditions to parental perceptions of the child's present condition, worries about the child not related to the present condition, and other personal worries. Assessments of 150 parents were made regarding parental anxiety, perceptions, and worries before and after a pediatric visit. A high-anxiety group (HAG) and low anxiety group (LAG) were derived from the 25% most and 25% least-anxious parents. A 2 x 2 repeated-measures analysis of variance revealed that both before and after the pediatric visit, parents in the HAG reported significantly poorer understanding of the child's condition and reported more worry about the reason for the visit, the child's behavior, finances, school or day care, relationships, employment, and future and past events than parents in the LAG (p < .003). The results suggest that factors unrelated to the child influence the anxiety of highly anxious parents of a child with a minor ailment. Actions that focus solely on the child and the child's condition could have a limited impact on anxiety. When faced with an anxious parent of a child with a minor condition, it appears sensible not only to be aware of perceptions and worries related to the child, but also other personal life concerns for that parent, the parent's general tendency to worry or become anxious, and how that parent is processing information. PMID- 8195433 TI - Perceived social support and adjustment of children with newly diagnosed cancer. AB - The negative impact on psychologic adjustment from the stress of living with newly diagnosed cancer is hypothesized to be affected by perceived social support. Thirty children with newly diagnosed cancer completed standardized assessment instruments measuring depressive symptoms, state anxiety, trait anxiety, social anxiety, general self-esteem, and perceived social support from classmates, parents, teachers, and friends. Their parents completed a standardized assessment instrument measuring internalizing and externalizing behavior problems. Perceived classmate, parent, and teacher social support were variously correlated with the psychologic adjustment parameters in the hypothesized direction of greater support predicting lower psychologic distress and higher self-esteem. Hierarchical multiple regression analyses identified perceived classmate social support as the most consistent predictor of adaptation, providing further evidence of the essential function of the social environment of the school setting in affecting the adjustment of children with newly diagnosed cancer. PMID- 8195434 TI - Specific neurocognitive deficits in Cornelia de Lange syndrome. AB - Cornelia de Lange Syndrome (DLS) is a dysmorphogenic disorder typically associated with severe mental retardation. This report describes a rare case with normal-range verbal intelligence and specific cognitive deficits suggestive of a developmental visuospatial disorder. This was apparent in selective deficits in the ability to integrate visual percepts, copy spatial configurations, and manipulate representations of objects in space. Visual memory and psychomotor skills were also impaired. These deficits occurred within the context of normal language abilities and language-related academic achievement. The observed pattern of neuropsychologic impairment, in addition to aspects of socioemotional development, was similar to that seen in children with developmental right hemisphere dysfunction. These findings suggest that the factors underlying DLS can be associated with fairly specific aberrations of cortical functioning. PMID- 8195435 TI - A behavioral analysis of dog bites to children. AB - Approximately one million dog bites occur yearly in the United States, and 60% to 70% of these are to children. Although the majority of dog bites are not serious, some are disfiguring or, on rare occasions, fatal. Bites are disruptive and stressful but also are preventable. This paper reviews the epidemiology of dog bites, examines the conditions under which bites occur, and discusses behavioral factors related to the dog and to the child that determine whether a bite will occur. Dog bites then are compared with other childhood injuries, and strategies for intervening both before and after a dog bite occurs are discussed. PMID- 8195436 TI - When the consequences of beliefs are defined as psychiatric entities. PMID- 8195437 TI - A meta-analysis of normal ranges for root surface areas of the permanent dentition. AB - The typical values and normal ranges of the permanent dentition root surface areas were estimated based on a meta-analysis of 4730 root surface area measurements collected from 22 published studies between 1950 and 1992. A typical dentition root surface area, excluding 3rd molars, was 75 cm2, and 95% of the dentitions had a total root surface area somewhere between 65 cm2 and 86 cm2. The prognostic significance of particular values of root surface areas for dental treatment outcomes requires further investigation. PMID- 8195438 TI - Clinical and histological evaluation of ligature-induced periodontitis in the domestic ferret. AB - The aim of this study was to evaluate the clinical and histological characteristics of ligature induced periodontitis in 12 domestic ferrets. On day 0, silk ligatures were placed at the gingival margin level of selected experimental teeth. The contralateral teeth served as control teeth. On day 14, 4 animals and on day 28, 8 animals were sacrificed. Clinical measurements including gingival index (GI), probing pocket depth (PPD) and probing attachment level (PAL) were taken in 5 animals on days 0, 14 and 28. Histological sections were prepared for light microscopy. The histometric measurements performed were (1) the distance between the cemento-enamel junction (CEJ) and the alveolar bone crest and (2) the distance between CEJ and connective tissue attachment level. The number of sections with root resorption areas was also observed. Cell counts were taken in 4 different areas. Clinical results showed, on days 14 and 28, a significant increase of the mean values of PPD and PAL at the experimental teeth when compared to the control teeth. The histometric results showed a significant loss of connective tissue attachment and bone loss in the experimental teeth on day 14. On day 28, the results were similar, although more sections with root resorption areas were observed in the experimental teeth. The predominant inflammatory cell in all the 4 experimental areas analyzed was polymorphonuclears (PMN), and they were mainly increased in areas closely related to the junctional epithelium. The results indicate that the domestic ferret may be used as an experimental animal in the ligature-induced periodontitis model. PMID- 8195440 TI - Dose response of chlorhexidine against plaque and comparison with triclosan. AB - The optimum dose of chlorhexidine delivered by mouthrinse, which balances efficacy against local side-effects, is generally considered to be in the region of 20 mg 2 x daily. Unfortunately, there have been few dose-response studies for chlorhexidine mouthrinses and for these, only limited details are published. The aims of this study were to determine the dose response of chlorhexidine to plaque inhibition and position a 0.1% triclosan rinse within this model. 28 subjects took part in this 7-treatment, double-blind, randomised cross-over 4-day plaque regrowth study. The rinses were 0.01%, 0.05%, 0.1% and 0.2% chlorhexidine, 0.1% triclosan and minus active controls for chlorhexidine and triclosan. On day 1 from a zero plaque baseline, volunteers suspended tooth-cleaning and commenced supervised 2 x daily rinsing with 10 ml volumes of the allocated rinses. On Day 5, plaque was scored by index and area. Treatment differences between the 7 rinses were highly significant. A clear dose-response pattern was seen for chlorhexidine with mean plaque scores decreasing with increasing dose. Even at 0.01%, chlorhexidine showed considerable and significant plaque inhibition compared to control. Triclosan at 0.1% showed limited plaque inhibition and less than 0.01% chlorhexidine. The findings of this study suggest that consideration could be given to low concentration chlorhexidine rinses as adjuncts to oral hygiene. PMID- 8195439 TI - Clinical and histological evaluation of ligature-induced periodontal breakdown in domestic ferrets immunosuppressed by Cyclosporin-A. AB - The aim of this study was to evaluate, clinically and histologically, the effect of Cyclosporin-A (CyA) on the progression of the periodontal breakdown in the domestic ferret, using the ligature induced periodontitis model. At the start of the experiment (day 0), silk ligatures were placed at the gingival margin level of experimental teeth. The contralateral teeth served as non-ligated control teeth. Clinical measurements included gingival index, probing pocket depth (PPD), probing attachment level (PAL) and gingival overgrowth (GO) and they were performed on days 0, 14 and 28. Cyclosporin-A, 10 mg/kg/d, was given subcutaneously from day 0 to 21, while in the last week there was a reduction of this dose to 5 mg/kg/d. Blood samples were taken on days 0, 14 and 28. On day 28 the animals were sacrificed. Histological sections were prepared for light microscopy. The histometric measurements performed were: (1) the distance between cemento-enamel junction and the alveolar bone crest and (2) loss of connective tissue attachment. The number of sections with root resorption areas was observed. Cell counts were taken in 4 different areas. The results showed, on days 14 and 28, a significant increase of the mean values of PPD and PAL at experimental teeth as compared to the control teeth. GO was present on experimental teeth on days 14 and 28. On day 28, the control teeth presented a very small increase in GO, mainly at the buccal sites of P4 and M1. The histometric results showed a significant loss of attachment and bone resorption in the experimental teeth. Root resorption was found in experimental teeth only. The predominant inflammatory cell in the 4 experimental areas was polymorphonuclears.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195441 TI - Clinical assessment of gingival hyperplasia in patients treated with nifedipine. AB - Gingival hyperplasia caused by the use of nifedipine has been extensively reported. In this paper, the gingiva of 18 patients suffering from cardiopathy and treated with nifedipine were compared with those of 10 patients with cardiac disorders who had not been treated with calcium antagonists and with a no treatment group of 12 patients. Nifedipine produced gingival hyperplasia, although patients who had not been treated with calcium antagonists also had mild hyperplasia. Hyperplasia first appeared in the interproximal areas, an observation which may be important for early detection. There was a direct correlation between the degree of hyperplasia and the bacterial plaque score. When we studied the influence of administration time and dose of nifedipine with the degree of hyperplasia, no statistically significant differences were found. PMID- 8195442 TI - The morphology of root fusion in Chinese adults (I). Grades, types, location and distribution. AB - The purpose of the present study was to investigate the morphology, extent, and distribution of root fusions in 1st and 2nd permanent molars in a Chinese population. The sample consisted of 158 maxillary and 151 mandibular extracted 1st and 2nd molars. Root fusion in molars was assessed by direct viewing and measuring the length of the root and root trunk with stereoscopic microscopy. Root fusion was graded by the extent of fusion and the number of affected surfaces. The main results were as follows: (1) the majority of root fusions affected upper and lower 2nd molars (39.7% and 28.1%, respectively); (2) the prevalence of maxillary roots with 1, 2 and 3 fusions was 55.2%, 31.3% and 13.4% respectively, and most of the root fusions affected the maxillary 2nd molars (65.7%); (3) the majority of mandibular root fusions affected the 2nd molars (89.2%), and were of grade III (48.7%); (4) in order of decreased prevalence, the grades of root fusion in 2nd molars were grades III, II and I; whereas in 1st molars they were grades I, II and III; (5) there were 44 (41.5%) and 19 (51.4%) complete root fusions (grade III) among 106 fused roots in maxillary molars and 37 fused roots in mandibular molars, respectively. PMID- 8195443 TI - Effects of denture-wearing habits on periodontal health of abutment teeth in patients with overdentures. AB - The effect of denture-wearing habits was studied in 31 overdenture wearers (17 day-and-night wearers, 14 day wearers) during a period of 5 years with controlled oral hygiene. Prior to prosthetic treatment, intensive instruction and motivation in oral hygiene were carried out and the patients were recalled 2-4 x yearly during the study period. Before treatment, mean plaque index (PlI) and gingival index (GI) were 1.5 and 1.6, respectively, in both groups of patients. During the study period, mean PlI and GI were 0.3-0.6 and 0.6-0.8, respectively, in the group of day wearers and 0.5-1.0 and 1.0-1.2, respectively, in the group of day and-night wearers. With regard to the GI, this difference was statistically significant. Furthermore, during the study period, 20% of the abutment tooth surfaces showed attachment loss (1-4 mm) in the group of day-and-night wearers against 8% of the tooth surfaces in the group of day wearers. This difference was statistically significant. During the 5 years, 40 carious lesions developed in the group of day-and-night wearers against 3 in the group of day wearers. The results of this study have shown that day-and-night wearing of dentures is a major periodontitis and caries risk factor in complete overdenture wearers with controlled oral hygiene. PMID- 8195444 TI - Periodontal diseases in HIV-infected patients. AB - Periodontal diseases may be the first clinical sign of human immunodeficiency virus (HIV)-infection. Since the immunosuppression and subsequent susceptibility may alter the responses of the oral tissues as well as the microflora, both periodontal treatment and result of therapy may be modified. The periodontal diseases in HIV-seropositive patients include common as well as less conventional forms of gingivitis and periodontitis, and bacterial, mycotic and viral infections are seen. Neoplasias may also involve the periodontium; most common are Kaposi's sarcoma and non-Hodgkin's lymphoma. Recent studies of unselected groups of patients indicate that periodontal health in at least some groups of HIV-seropositive patients is better than previously reported. PMID- 8195445 TI - Amlodipine-induced gingival overgrowth. AB - Amlodipine is a calcium channel blocker used in the management of angina and hypertension. We report 3 cases of gingival overgrowth in adult dentate patients associated with chronic usage of this drug. Gingival changes occurred within 3 months of dosage and appeared to be compounded by the patient's existing periodontal condition. In all 3 patients, there was sequestration of amlodipine in their crevicular fluid. The significance of this finding in relation to the pathogenesis of this unwanted effect remains to be elucidated. PMID- 8195446 TI - Comparative reproducibility of proximal probing depth using electronic pressure controlled and hand probing. AB - This investigation assessed the effect of an electronic pressure-sensitive probe on the reproducibility of probing-depth measurement. Clinical measurements were made at the mesial and distal aspects of all teeth from the buccal and palatal or lingual aspects. Probing was carried out either in a conventional manner using gentle pressure referred to as hand probing or using an electronic pressure sensitive probe set at 25 g and referred to as pressure-controlled probing. Probing-depth recordings were repeated for one randomly selected quadrant in each subject with random application of the 4 different combinations of pressure controlled and hand probing. A total of 2584 replicate pairs of probing depth measurements were recorded on 4 proximal surfaces in 646 teeth in 100 adult subjects. The majority (98%) of all repeated measurements were within 1 mm of the initial values. The highest levels of agreement resulted when the same probing method was used at both examinations with electronic pressure-controlled probing being superior to hand probing regardless of tooth position or site. Duplicate measurements recorded with combinations of hand and pressure-controlled probing showed significant systematic bias towards shallower pocket depths with electronic pressure-controlled probing. PMID- 8195447 TI - Variance component modeling of attachment level measurements. AB - The purpose of this study was to investigate the influence of within subject and within tooth variability of attachment-level measurements on hypothesis testing. Full-mouth attachment-level measurements were obtained at 4 sites per tooth in early onset periodontitis subjects (both localized N = 89 and generalized N = 139) and adult periodontitis subjects (N = 309). Variance component models utilizing iterative generalized least squares were employed to estimate the % of variance distributed at the level of the site, tooth and subject in the 3 subject populations. The data indicate that a significant % of the variance is distributed within the tooth and the subject. Ignoring the variance attributable to teeth or subjects can result in inappropriately low type I error rates for hypothesis testing. Thus, both the subjects and the tooth must be considered in the modeling of attachment level measurements. Also in studies in which a limited number of samples are taken, data analysis would be simplified if these samples were taken from different teeth. PMID- 8195448 TI - Comparison of 2 chlorhexidine mouthwashes on plaque regrowth in vivo and dietary staining in vitro. AB - Until recently, the few available chlorhexidine mouthrinse products have been 0.2% formulations. However, concentrations of 0.12% chlorhexidine appear as effective as 0.2%, if the volume of the rinse is increased to 15 ml. Since the mere incorporation of chlorhexidine in a formulation does not guarantee availability of the antiseptic, it would seem reasonable to evaluate or compare all products. This is particularly the case when other ingredients, such as fluoride are added. The 1st study compared the effect of a 0.12% chlorhexidine rinse with a 0.12% chlorhexidine/0.022% sodium fluoride rinse for effects on plaque regrowth. The study was a 7-day, blind, randomised, 2-cell cross-over design with a baseline control run in period, in which 18 subjects participated. Both chlorhexidine products significantly reduced plaque compared to control but the chlorhexidine fluoride rinse was less effective than the chlorhexidine only rinse. The 2nd study assessed the propensity of the chlorhexidine rinses to induce dietary staining in vitro. For the chlorhexidine fluoride rinse, this was less than the other 0.12% rinse and a commonly used 0.2% product. The data in vivo and in vitro suggest reduced chlorhexidine availability from the chlorhexidine fluoride product which appears to cause some loss of efficacy. PMID- 8195449 TI - Collagenase, gelatinase and elastase activities in sulcular fluid of osseointegrated implants and natural teeth. AB - Proteinases play a key role in the physiological degradation and remodelling of the periodontal tissues. The role of these enzymes in tissue remodelling remodelling in connection with the insertion of dental endosseous implants has not been elucidated. Therefore, the aim of the present study was to identify the eventual presence of collagenase, gelatinase and elastase activities in periimplant sulcus fluid (PISF) of osseointegrated implants. Gelatinolytic activity in the samples was studied with gelatin-zymograms. Collagenase activity and its susceptibility to tetracycline-inhibition were monitored with SDS polyacrylamide gel electrophoresis and laser densitometry, and elastase activity with synthetic substrate. Low activities of elastase and collagenase were detected in both PISF of osseointegrated implant patients and gingival crevicular fluid (GCF) of the control patients whereas significantly higher activities were detected in GCF of adult periodontitis patients. Also the profiles of gelatinases were similar in PISF of osseointegrated implant patients and GCF of the controls, but differed from the profile of active gelatinases present in GCF of adult periodontitis patients. The similar activities/characteristics of these proteinases in both periimplant sulcus fluid of healthy dental implants and GCF of healthy natural teeth suggest that they comprise the major proteinases for both periodontal and periimplant tissue remodelling or destruction. PMID- 8195450 TI - Blood pressure and heart rate response of panic disorder patients receiving imipramine in a dose-response treatment paradigm. AB - This article reports the effects of imipramine on heart rate and blood pressure in panic disorder patients who participated in an 8-week double-blind dosage response treatment protocol. At the end of a placebo baseline, patients were randomly assigned to placebo or one of three weight-adjusted imipramine dosages: low (0.5 mg/kg per day), medium (1.5 mg/kg per day), or high (3.0 mg/kg per day). It was demonstrated that imipramine had no significant effect on sitting or standing diastolic or systolic blood pressure. Although there was a trend toward a systolic blood pressure drop with positional change, it did not reach statistical significance. There were no significant changes in diastolic blood pressure with postural change. Imipramine did increase sitting and standing heart rate without revealing a clear dosage correlation. In contrast to the pretreated state, the reflex heart rate response to postural change was significantly increased in the posttreatment state, also in a dosage-independent manner. Within the high-dose imipramine group, the baseline sitting to standing heart rate increase was significantly higher in those who dropped out because of drug side effects compared with those who remained. Evidence from this study suggests that imipramine has a dosage-independent effect on resting and reflex heart rate. Future studies should consider postural heart rate reactivity as a potential measure of intolerance to the side effects of high doses of imipramine. PMID- 8195451 TI - Clonazepam in the treatment of panic disorder: a double-blind, placebo-controlled trial investigating the correlation between clonazepam concentrations in plasma and clinical response. AB - Thirty-two outpatients with a DSM-III diagnosis of panic disorder or agoraphobia with panic attacks were randomly assigned to 4 weeks of treatment with clonazepam or placebo, after a 1-week placebo washout period. Twenty-nine patients entered the double-blind phase of the study and were eligible for intent-to-treat analysis. Clonazepam-treated patients experienced significantly fewer panic attacks, and these were of lesser intensity and short duration than those in placebo-treated patients (p < 0.001). Clonazepam was also superior to placebo with respect to symptoms of anxiety and depression (p < 0.001). The mean dose of clonazepam at week 4 was 2.2 mg (standard deviation, 0.7 mg). There was significant (p < 0.05) correlation between drug concentration in plasma and decrease in the global measure of the severity of panic disorder (r = 0.68); similar trends were seen for the decreases in frequency (r = 0.60) and severity (r = 0.55) of panic attacks, but not between concentration in plasma and decline in generalized anxiety. The most common adverse event was drowsiness, which occurred in 9 of 13 clonazepam-treated patients. PMID- 8195452 TI - Clozapine and metabolites: concentrations in serum and clinical findings during treatment of chronically psychotic patients. AB - Clozapine (CLZ) and metabolites norclozapine and clozapine-N-oxide were assayed with a new, sensitive (2 pmol), and selective method in 68 serum samples from 44 psychotic subjects, 20 to 54 years old, ill 16 years, and treated with CLZ for 2.2 years (currently at 294 mg, 3.4 mg/kg daily). CLZ levels averaged 239 ng/ml (0.73 microM; 92 ng/ml per mg/kg dose) or 48% of total analytes (norclozapine = 41% [91% of CLZ] and clozapine-N-oxide = 11%); metabolite and CLZ levels were highly correlated (rs = 0.9), and CLZ levels varied with daily dose (rs = 0.7). Sampling twice yielded similar within-subject analyte levels (r = 0.8 to 0.9; difference = 24% to 33%). Range and variance narrowed when levels were expressed per weight-corrected dose (ng/ml per mg/kg). Levels per dose were 40% higher in nonsmoking women than men, despite a 60% lower milligram per kilogram dose in women, and did not vary by diagnosis or age in this limited sample. Fluoxetine increased serum CLZ analytes by 60%; valproate had less effect. Patients rated treatment very positively; observer-assessed benefits typically were more moderate. Common late side effects were sialorrhea (80%), excess sedation (58%), obesity (55% > 200 lb), mild tachycardia (51%), constipation (32%), and enuresis (27%); there were no seizures or leukopenia. There was little evident relationship of drug dose or serum level to current clinical measures or side effect risks. PMID- 8195453 TI - Buspirone's efficacy in organic-induced aggression. AB - The objectives of this study were to (1) identify and characterize hospitalized patients with an organic-related psychiatric diagnosis who had received buspirone therapy and (2) assess the effect of buspirone on aggressive behaviors. A retrospective medical records review was conducted on all patients who were admitted to our psychiatric/rehabilitation facility over a 36-month period and who had received buspirone therapy. Monthly behavioral therapy records were used to determine the quality and quantity of aggressive-related behaviors. Study endpoint was reached in each subject when buspirone was discontinued or when records were unavailable. Twenty subjects, ranging in age from 15 to 55 years old (mu = 26.1 +/- 9.8), were identified for study. Nine (90%) of 10 subjects for whom data were available for at least 3 months showed an improvement in behavior by study endpoint, and 6 (60%) showed at least a 50% reduction in behavioral symptoms by study endpoint. Results from this study suggest that buspirone is well tolerated and may be effective in the treatment of aggressive and other maladaptive behaviors in individuals with an organic component to their psychiatric illness, particularly traumatic brain injury. Prospective, controlled trials are needed to validate these findings. PMID- 8195454 TI - Steroid hormones and Tourette's syndrome: early experience with antiandrogen therapy. AB - We report here the first use in Tourette's syndrome of the nonsteroidal androgen receptor blocking agent flutamide. One man and one woman underwent open trials of the medication, and a second man participated in a placebo-controlled, double blind crossover trial. Improvement in tic symptoms ranged from 45 to 60%. The improvement was sustained in the woman during daily flutamide use and in one man during its intermittent use. One man's symptoms became refractory to treatment after 5 weeks of flutamide use, whereas the woman became depressed and had protracted diarrhea during her treatment. PMID- 8195455 TI - Physical disability and social phobia. AB - The DSM-III-R excludes persons with socially phobic symptoms secondary to axis III conditions from the diagnostic category of social phobia. This exclusion exists without empirical basis. A series of eight clinical cases is presented in which patients suffered from excessive levels of secondary social anxiety relative to their disfiguring or disabling physical conditions. All subjects had a good response to the monoamine oxidase inhibitor phenelzine, which enabled them to live in a less-inhibited and less-restrictive manner. Their medication response to monoamine oxidase inhibitors parallels the psychopharmacologic response patterns of generalized or DSM-III-R social phobics. This study suggests a novel application of the drug phenelzine for a patient group formerly overlooked with regard to treatment options. The similarity of this group's psychopharmacologic responsivity and clinical characteristics to those of DSM-III R social phobics also lends support to the relaxation of the axis III exclusion in DSM-IV's definition of social phobia. PMID- 8195456 TI - Sertraline and isocarboxazid cause a serotonin syndrome. PMID- 8195457 TI - Grand mal seizures associated with the use of fluoxetine. PMID- 8195458 TI - Tardive dyskinesia-like syndrome associated with lithium and carbamazepine. PMID- 8195459 TI - Tardive akathisia, tardive dyskinesia, and serum iron status. PMID- 8195460 TI - Sleepwalking associated with zolpidem. PMID- 8195461 TI - Phototherapy-induced hot flushes. PMID- 8195462 TI - A reevaluation of the clinical characteristics of clozapine-induced agranulocytosis in light of the United States experience. PMID- 8195463 TI - Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine. AB - The pharmacokinetic interactions of sertraline and fluoxetine with the tricyclic antidepressant desipramine were studied in 18 healthy male volunteers phenotyped as extensive metabolizers of dextromethorphan. Concentrations in plasma were determined after 7 days of desipramine (50 mg/day) dosing alone, during the 21 days of desipramine and selective serotonin reuptake inhibitor (SSRI) coadministration (fluoxetine, 20 mg/day; sertraline, 50 mg/day), and for 21 days of continued desipramine administration after SSRI discontinuation. Desipramine Cmax was increased 4.0-fold versus 31% and AUC0-24 was increased 4.8-fold versus 23% for fluoxetine versus sertraline, respectively, relative to baseline after 3 weeks of coadministration. Desipramine trough concentrations approached baseline within 1 week of sertraline discontinuation but remained elevated for the 3-week follow-up period after fluoxetine discontinuation. Concentrations of SSRIs and their metabolites correlated significantly with desipramine concentration changes (for fluoxetine/norfluoxetine, r = 0.94 to 0.96; p < 0.001; for sertraline/desmethylsertraline, r = 0.63; p < 0.01). Thus, sertraline had less pharmacokinetic interaction with desipramine than did fluoxetine at their respective, minimum, usually effective doses. PMID- 8195464 TI - A comparison of venlafaxine, trazodone, and placebo in major depression. AB - A double-blind, placebo-controlled trial was undertaken to compare the safety and efficacy of venlafaxine and trazodone in patients with major depression. Two hundred twenty-five patients entered an initial 6-week treatment phase, and 149 completed it. Ninety-six patients who were responders continued in a 1-year, double-blind, long-term phase during which they received the same medication and doses they had during the short-term phase. Both active treatments were significantly more effective than placebo on some measures during the short-term study, but venlafaxine produced more improvement in the cognitive disturbance and retardation factors on the Hamilton Rating Scale for Depression. Trazodone was more effective against the sleep disturbance factor. Patients on venlafaxine were most likely to enter the long-term phase and to remain in the trial longest. The side effect profiles of the three treatment groups were compared. Venlafaxine was most likely to cause nausea, whereas trazodone was associated with the most dizziness and somnolence. PMID- 8195465 TI - In situ hybridization detection of trkA mRNA in brain: distribution, colocalization with p75NGFR and up-regulation by nerve growth factor. AB - In situ hybridization techniques were used to examine the distribution and the nerve growth factor (NGF) regulation of trkA mRNA in the adult rat brain in order to identify neurons in discrete regions of the brain that may be NGF responsive. In agreement with previous studies, trkA mRNA was detected within cells located in the medial septum (MS), diagonal band of Broca (DBB), and caudate. trkA mRNA was also detected in many other regions of the brain, including the nucleus basalis of Meynert, substantia innominata, paraventricular nucleus of the thalamus, interpeduncular nucleus, prepositus hypoglossal nucleus, vestibular nuclei, raphe obscuris, cochlear nucleus, sensory trigeminal nuclei, and gigantocellular as well as perigigantocellular neurons in the medullary reticular formation. By combining in situ hybridization detection of trkA mRNA with immunocytochemical detection of p75NGFR, it was determined that the vast majority (> 90%) of the trkA mRNA-containing cells detected in the MS and DBB also express p75NGFR. Likewise, the vast majority of p75NGFR-IR cells detected in the MS and DBB expressed trkA mRNA. Intracerebroventricular infusions of NGF into the third ventricle adjacent to the preoptic area resulted in a 58% increase in relative cellular levels of trkA mRNA in the horizontal limb of the DBB. These data provide evidence that both p75NGFR and trkA are expressed by NGF-responsive neurons in the MS and DBB. In addition, we note that areas that contained trkA mRNA and that also have been reported to contain p75NGFR are areas where high affinity NGF binding sites have been observed autoradiographically, whereas areas that contain either trkA or p75NGFR alone are areas where no high-affinity NGF binding has been reported. Together, these findings suggest that both trkA and p75NGFR play an important role in the formation of high-affinity NGF receptors in brain and, furthermore, suggest that NGF may have physiological effects within many regions of the brain outside of the basal forebrain. PMID- 8195466 TI - Gonadal steroids regulate immunoreactive tachykinin in the ventromedial nucleus of the rat hypothalamus. AB - The ventromedial nucleus of the hypothalamus (VMH) is an important site in the mediation of female receptive behavior (lordosis); however, the sequence of events that eventually facilitate this estrogen-dependent behavior is only partially understood. Here, evidence is presented, suggesting that an interaction between gonadal steroids and tachykinin peptides is involved. Tachykinin immunoreactive (TACir) neurons were distributed throughout the anterior (VMHa), dorsomedial (VMHdm), central (VMHc), and ventrolateral (VMHvl) subdivisions in the adult male and female rat. Numbers of cells in the VMH of intact males and males that had been castrated for three weeks were similar. Among females, numbers of TACir cells in the VMHvl were significantly increased over numbers seen in ovariectomized females by a two day (1.5 x) and by a two week (1.6 x) exposure to estrogen. In the VMHa, numbers of TACir cells were also significantly higher in females that received replacement estrogen compared to ovariectomized females. Since estrogen concentration by TACir neurons is common in the VMHvl and rare in the VMHa, estrogen may have both direct and indirect effects on tachykinin synthesis. In the caudal pole of the VMH, staining intensity of TACir fibers varied with endocrine state. In intact males, castrated males, and ovariectomized females, fibers were lightly stained. In females exposed to estrogen for two days, fibers were moderately intense, and in females exposed to estrogen for two weeks, they formed a darkly stained plexus. These responses to estrogen suggest that production of tachykinin peptides in the VMH is involved in facilitation of female typical sexual behavior. PMID- 8195467 TI - Reevaluation of area 3b in the cat based on architectonic and electrophysiological studies: regional variability with functional and anatomical consistencies. AB - Most anatomical and electrophysiological studies of the cat primary somatosensory cortex rely on Hassler and Muhs-Clement's (J. Hirnforsch. 6:377-420, 1964) cyto- and myeloarchitectonic description distinguishing area 3a from area 3b; however, discrepancies in the delineation of these areas in published studies suggest that many workers have found it difficult to apply those criteria systematically. We examined the cytoarchitecture of area 3b in Nissl stained sagittal sections from which electrophysiological data had been obtained prior to sacrifice. Rostrocaudal rows of electrode penetrations placed at different mediolateral positions in the gyrus located regions responsive to stimulation of either cutaneous or deep structures. Small electrolytic lesions allowed these data to be related to the cytoarchitecture. A systematic study throughout the trunk and limb representations found cutaneous responses in cortical regions characterized by a thick and cell-dense granular layer IV, however these same regions had a variable population of medium-sized and/or large pyramidal cells in layer V. Pyramidal cells were practically absent from the forelimb representation, but were present to varying degrees in the trunk and hindlimb representations. Moreover, the relative thickness and cell-density in layer IV were greater in the forelimb than in the hindlimb representations. Deep responses were found in cortex characterized by a thinner layer IV. Since the characteristics of layer V in area 3a were variable, it was less useful for identification of the border between areas 3a and 3b. Clear changes in the intensity and laminar distribution of acetylcholinesterase staining occurred between areas 3a and 3b, making this a useful adjunct to the Nissl stain. PMID- 8195468 TI - Neurotensin receptor expression in the rat forebrain and midbrain: a combined analysis by in situ hybridization and receptor autoradiography. AB - The aim of the present study was to examine the distribution of the levocabastine insensitive high-affinity neurotensin binding sites in the rat forebrain and midbrain in relation to the distribution of the cloned neurotensin receptor mRNA by using a combination of both high-resolution in vitro receptor autoradiography and in situ hybridization approaches. Groups of cells rich in neurotensin receptor mRNA were observed in the basal forebrain nuclei, the ventral tegmental area, the substantia nigra and in the interfascicular and caudal linear nuclei and the retrorubral field. Cells expressing lower levels of neurotensin receptor mRNA were found in several subdivisions of the cortex; the dentate gyrus; the septofimbrial, suprachiasmatic, medial habenular, and mammillary nuclei; the dorsal part of the lateral septum; the zona incerta; and the dorsomedial and perifornical hypothalamic areas. Most of the brain areas containing neurotensin receptor mRNA demonstrated a selective association of neurotensin binding sites with neuronal cell bodies. In contrast, in several telencephalic and diencephalic structures, the presence of neurotensin binding sites was not correlated with that of neurotensin receptor mRNA, suggesting that neurotensin receptors were mainly located on axon terminals. This study provides a better understanding of the anatomical organization of neurotensin receptor expressing systems in the rat brain and gives further insight into the pre- vs. postsynaptic location of neurotensin receptors in various brain regions. Moreover, it indicates that all neurons expressing the cloned neurotensin receptor harbour neurotensin binding sites on their perikaryal membrane. PMID- 8195469 TI - Mucosal acidification and an acid microclimate in the hen colon in vitro. AB - Experiments were performed on isolated, stripped colonic epithelia of low-salt adapted hens (Gallus domesticus) in order to characterize acid secretion by this tissue. With symmetric, weak buffer solutions, colonic epithelia acidified both mucosal and serosal sides. Titration measurements of the mucosal acidification rate (pH-stat technique) averaged 1.63 +/- 0.25 microEq.cm-2.h-1. Mucosal acidification was also evident in colons from high-salt-adapted birds and in low salt-adapted coprodeum, but was completely abolished in the high-salt coprodeum. Mucosal acidification by low-salt-adapted colonic epithelium was unaffected by sodium replacement, mucosal amiloride (10(-3) mol.l-1), and serosal ouabain (5 x 10(-4) mol.l-1), although all three treatments significantly reduced or reversed the short-circuit current. Acetazolamide (10(-3) mol.l-1, serosal) reduced mucosal acidification by 15% and simultaneously increased short-circuit current by a similar amount. Colonic epithelia incubated in glucose-free solutions had significantly lower acidification rates (0.59 +/- 0.13 microEq.cm-2.h-1, P < 0.002 versus controls) and addition of glucose (15 mmol.l-1), but not galactose, partially restored acidification to control levels. Anoxia (N2 gassing) completely inhibited short-circuit current, but reduced acidification by only 30%. A surface microclimate pH, nearly 2 pH units more acidic than the bath pH of 7.1-7.4, was measured in low-salt-adapted colon and coprodeum. The acid microclimate of both tissues was partially attenuated by adaptation to a high salt diet. Colonic microclimate pH was dependent on the presence of glucose and sensitive to the bath pH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195471 TI - Kidney concentrating ability of a subterranean xeric rodent, the naked mole-rat (Heterocephalus glaber). AB - The naked mole-rat (Heterocephalus glaber) is a strictly subterranean mammal inhabiting the arid zones of north-east Africa. These animals have no access to free water and water balance thus might be facilitated by regulating renal water loss. The urinary concentrating ability of the naked mole-rat was determined using five dietary manipulations in which both water and salt content were altered. "Control" animals (n = 7) received a high quality protein cereal mixed to a thin paste with water (1 g cereal: 8.5 g water). Water stress was induced by reducing the water content of the diet by either 50% (n = 7) or 65% (n = 7). Salt loading was facilitated by replacing the water with the same volume of either 0.9% salt (n = 7) or 3.0% salt (n = 4) solutions. Changes in body mass, food consumption and urine volume were measured daily. The effect of diet on osmolality and electrolyte concentrations of urine and plasma were determined on termination of the diet trials. Although energy intake was not reduced, naked mole-rats lost body weight with both water stress treatments. Urine volume voided per day decreased significantly with both water stress treatments (P < 0.05), such that the most extreme water stress led to an 80% reduction in urine volume. Mildly salt-loaded animals gained weight, yet underwent a sodium diuresis, as indicated by a 1.3-fold increase in the daily volume of urine voided (P < 0.05). Maximum urine concentration (1521 +/- 250 mmol.kg-1) was achieved with mild water stress and was 4.6 +/- 0.9 times that of plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195470 TI - Effect of unilateral surgical denervation of brown adipose tissue on uncoupling protein mRNA level and cytochrom-c-oxidase activity in the Djungarian hamster. AB - The bilateral lobe of interscapular brown adipose tissue of the Djungarian hamster was unilaterally denervated in order to study the role of the sympathetic innervation for maintenance and cold-induced increase of non-shivering thermogenesis. Denervation decreased the noradrenaline content of brown adipose tissue to less than 9% of the intact contralateral pad. This low noradrenaline level was maintained for 1-14 days after denervation. First, to study the role of the sympathetic innervation of brown adipose tissue in the maintenance of the high thermogenic capacity characteristic of the cold acclimated state, brown adipose tissue was denervated in hamsters either kept at thermoneutrality or acclimated to 5 degrees C ambient temperature for 4 weeks. Cold-acclimated hamsters had elevated levels of uncoupling protein messenger ribonucleic acid (8.1-fold) and cytochrom-c oxidase-activity (3-fold). Denervation of brown adipose tissue decreased uncoupling protein-messenger ribonucleic acid level and cytochrom-c-oxidase-activity as compared to the intact pad in thermoneutral and in cold-acclimated hamsters. However, in cold-acclimated hamsters uncoupling protein-messenger ribonucleic acid level and cytochrom-c-oxidase-activity in denervated brown adipose tissue both were maintained on an elevated 6-fold higher level as compared to thermoneutral controls. Second, to study the role of the sympathetic innervation of brown adipose tissue in the cold-induced increase in thermogenic capacity, hamsters were denervated prior to cold acclimation and responses were measured after 3 and 14 days of cold exposure. Uncoupling protein messenger ribonucleic acid level and cytochrom-c-oxidase-activity of intact brown adipose tissue increased after 14 days cold acclimation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195472 TI - Longevity and antioxidant enzymes, non-enzymatic antioxidants and oxidative stress in the vertebrate lung: a comparative study. AB - It has been proposed that antioxidants can be longevity determinants in animals. However, no comprehensive study has been conducted to try to relate free radicals with maximum life span. This study compares the lung tissue of various vertebrate species--amphibia, mammals and birds--showing very different and well known maximum life spans and life energy potentials. The lung antioxidant enzymes superoxide dismutase, catalase, Se-dependent and non-Se-dependent glutathione peroxidases, and glutathione reductase showed significantly negative correlations with maximum life span. The same was observed for the lung antioxidants, reduced glutathione and ascorbate. It is concluded that a generalized decrease in tissue antioxidant capacity is a characteristic of longevous species. It is suggested that a low rate of free radical recycling (free-radical generation and scavenging) can be an important factor involved in the evolution of high maximum animal longevities. A low free-radical production could be responsible for a low rate of damage at critical sites such as mitochondrial DNA. PMID- 8195473 TI - Search for rhythmicity during hibernation in the European hamster. AB - Temporal patterns of hibernation were studied by continuous monitoring of body temperature by radiotelemetry over 6 months in European hamsters, Cricetus cricetus, at constant temperature and photoperiod. Entrances into hibernation occurred mostly at the end of the night (0000-0800 hours), while arousals were randomly distributed between day and night. This is at variance with a control of bout duration by a clock with a period of 24 h. Consequently, the timing of entrances implies a phase-resetting of the circadian clock on each arousal. Persistence of circadian rhythmicity with a period different from 24 h during deep hibernation was investigated examining whether the durations of torpor bouts were integer multiples of a constant period. A non-parametric version of the classical contingency test of periodicity was developed for this purpose. Periods ranging from 21 to 29 h were tested. Nine animals out of ten showed at least one significant period in this range (P < 0.01), either below 24 h (21.8 +/- 0.5 h, n = 4) or above (27.3 +/- 0.5 h, n = 7). However, we have found a theoretical model of bout durations for which the contingency test of periodicity sometimes gives false significant results. This indicates that the power of the test is weak. With this reservation our results suggest that a circadian oscillator controls the duration of a bout of hibernation, which would occur after an integer, but variable and possibly temperature-dependent number of cycles. PMID- 8195474 TI - Shear bond strength of resin bonded ceramic after different try-in procedures. AB - Final cementation of porcelain laminate veneers may require a previous colour match try-in. The purpose of this in vitro study was to evaluate the effect on shear bond strength of resin bonded to porcelain after the application of different try-in procedures. Forty porcelain specimens were fabricated, flattened with 600 grit SiC, etched with hydrofluoric acid and silane treated. After 24 h the specimens were divided into four groups at random and prior to bonding of a dual cure resin composite button were treated as follows: Group 1, no treatment (control); Group 2, non-activated resin applied for 5 min, cleaned in acetone for 3 min; Group 3, as for Group 2, with silane reapplied; Group 4, as for group 3, but re-etched for 30 s before reapplication of silane. After bonding the specimens were stored in water at room temperature for 7 days. Shear bond strength data were as follows: Group 1, 18.6 +/- 1.6; Group 2, 15.9 +/- 1.7; Group 3, 16.7 +/- 2.6; Group 4, 15.3 +/- 3.0 MPa. Fractured surfaces examined, under light microscopy and scanning electron microscopy (SEM), showed cohesive failure within the porcelain in all cases. The reduction in mean bond strength after application of a try-in resin was significant in Groups 2 and 4 compared with the control (ANOVA P < 0.05). No other significant differences were measured. In conclusion a single reapplication of silane maintained the bond strength of resin to porcelain when final cementation was preceded by a try-in procedure and cleaning. PMID- 8195475 TI - Cervical marginal fit of proximal amalgam restorations. AB - This study investigated the relationship between the adaptation, apical location and gap width of the cervical margin of proximal amalgam restorations. Three hundred and seventeen proximal cervical margins were studied in 243 extracted teeth. The restorations were categorized as 'flush fitting'; 'small overhang', or 'large overhang', based on examination with a Cross calculus probe. After trimming the overhangs to make the restorations flush with the tooth surface, the gap width was measured. In addition, the location of the cavity margin was measured relative to the amelocemental junction (ACJ), and the data were further grouped according to whether the restoration finished apical to the ACJ, less than 1.5 mm coronal to it, or more than 1.5 mm coronal to it. All measurements were made with a Reflex Microscope. Analysis of variance with the Scheffe multiple range test indicated that: the mean gap width of large overhanging restorations was significantly greater than that of small overhanging or flush fitting restorations (P < 0.001); the mean gap width of restorations which finished on the root surface was significantly greater than that of those restorations which finished on the enamel surface at more than 1.5 mm from the ACJ (P < 0.002); and large overhanging restorations were located further apically than small overhanging restorations which were, in turn, located further apically than flush fitting restorations (P < 0.0001). Furthermore, discriminant analysis indicated that the location of the cervical margin had more influence on gap width than the presence of an overhang (R2 = 3.6%; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195476 TI - Analysis of optical transmission by 400-500 nm visible light into aesthetic dental biomaterials. AB - The penetration of visible light into dental biomaterials is an essential factor in photoinitiation of setting reactions and in the optical aspects of dental aesthetics. Light of visible blue wavelengths, 400-500 nm, has been applied at normal angles to 0.2-5.0 mm sections of human dentine and representative ceramic, polymerceramic composites and hybrid glass-polyalkenoate materials. The integrated optical transmission has been determined for each material section. The data have been converted to absorbance values and analysed to check for mathematical conformity to the Beer-Lambert Law. It is found that conformity (typically, P < 0.01) to the linear Beer-Lambert Law is only attained by making a substantial correction for the intensity of light reflected from the surface of aesthetic biomaterials. This is otherwise expressed by distinguishing between true and apparent absorbance. From linear regression of apparent absorbance with section thickness, the intercept depends upon the logarithm of the surface reflection ratio. This factor ranges from 30% to 90% in the materials investigated. It follows that there is a high degree of inefficiency in the transmission of visible light into and through aesthetic biomaterials for the purposes of photoactivation using existing technology. Means by which this limitation and inefficiency may be reduced are discussed. While the reflectivity of aesthetic biomaterials has been perceived by dental practitioners, the magnitude of this effect and its implications in connection with light-cured materials have not been analysed and emphasized hitherto. PMID- 8195477 TI - Replacement of missing cusps: an in vitro study. AB - One of the commonest methods of replacing a missing cusp, a pinned amalgam restoration, was compared with three adhesive restorative techniques, two of them with additional pin retention. All the teeth were subjected to occlusal/lateral forces and loaded to fracture in an Instron testing machine. A layered restoration of glass ionomer cement replacing the dentine, and resin composite replacing the enamel, without pins required more force to fracture than any of the other techniques including the pinned amalgam restoration. A composite restoration with dentine bonding agent and additional pin retention was second best and significantly better than the pinned amalgam restoration. A cermet restoration with additional pin retention required slightly less force to fracture than pin-retained amalgam restorations, but not significantly so. PMID- 8195478 TI - Measurement methods for adhesion to dentine: the current status in Japan. AB - Adhesive test in vitro is performed to evaluate bonding materials. This paper describes methods of measuring adhesion to dentine currently used in Japan, and considers advantages and disadvantages. Various tests are used in Japan. Many factors-dentine substrate, storage conditions, bond strength test method-affect bonding to dentine. Bond strength test methods employed are divided into: tensile bond test and shear bond test. The test method used for the best prediction of clinical performance in bond strength evaluation is discussed. There has also been interest in bonding stability. At present, it may be difficult to propose an optimal standardized measuring method. Standardized experimental conditions in vitro which can simulate conditions in vivo are still under investigation. PMID- 8195479 TI - Clinical relevance of the formulation and testing of dentine bonding systems. AB - The formulation of a dentine bonding system requires several properties which control the performance of the adhesive film. Numerous tests have been introduced for material screening purposes. Understanding the clinical relevance of the formulation principles and laboratory testing pertinence to in vivo conditions are of great importance in order to establish meaningful criteria for product development and evaluation. PMID- 8195480 TI - What is the clinical relevance of in vitro dentine permeability tests? AB - This paper reviews the effect of dentine permeability on the bond strength of dentinal bonding systems and its relationship with the morphology of dentine. Deep dentine is more permeable than superficial dentine. Demineralization of dentine surfaces with acidic conditioners significantly increases permeability with respect to dentine covered by a smear layer. Several primers apparently leave intact smear layers as seen by scanning electron microscopy, but greatly increase the fluid filtration towards the dentine suggesting several modifications in the smear layer. Previous generations of dentinal bonding systems have been shown to be extremely sensitive to dentine humidity and permeability. By contrast, contemporary dentine bonding systems are not influenced by wet dentine. According to the Poiseuille-Hagen equation, small changes in the functional diameter of dentinal tubules can greatly modify permeability. Restorative materials are able to reduce the permeability of prepared dentine subject to location. PMID- 8195481 TI - Intraoral humidity during operative procedures. AB - Results of dentine adhesion studies are influenced by many factors such as intrinsic and extrinsic dentine wetness. Relative air humidity and temperature are extrinsic environmental factors whose influence on dentine bonding capability is not precisely known. It was the aim of this study to gain an understanding of these factors as present in the mouths of patients and as influenced by several variables. In six different experiments the influence of application of a rubber dam, high and low relative humidity in the dental surgery, nose and mouth breathing and tooth drying was investigated. The results show that without application of a rubber dam there was no statistically significant difference in temperature for the variables nose and mouth breathing and tooth drying (mean 27.7 +/- 1.5 degrees C). Only the difference in relative air humidity of the dental surgery was statistically significant. With the application of a rubber dam the relative air humidity and temperature were essentially the same as the dental surgery conditions. It is concluded that without rubber dam the intraoral environment in which bonding procedures are to be performed is comparable with a high humidity climate such as that of Central Africa or the South Pacific. PMID- 8195482 TI - Bond strength of six dentinal adhesives. AB - This study compared the shear bond strengths on dentine of five dentine adhesives against Scotchbond 2 as a control. Dentine specimens from 225 extracted human permanent molar teeth were used in a matched-pair design, such that 45 tooth sides were treated along with the matching control for each of the five test materials. Shear bond strength testing was conducted 24 h after the completion of each specimen. Results showed that mean force (MPa) for the materials were: XR Bond, 17.1 +/- 5.1; Scotchbond Multi-Purpose, 15.9 +/- 6.5; Syntac, 13.5 +/- 8.6; All-Bond 2, 6.2 +/- 4.1; Scotchbond 2 (control composite score), 4.9 +/- 3.0; Denthesive, 3.4 +/- 1.7. Matched pair t-test comparisons with Scotchbond 2 control were: XR Bond, P = 0.0005; Scotchbond Multi-Purpose, P = 0.0005; Syntac, P = 0.0005; All-Bond 2, P = 0.0368; Denthesive, P = 0.005. Analysis of variance determined a statistically significant difference (P = 0.05) between the means of the bond strengths, which fell into four groups: Group A, XR Bond and Scotchbond Multi-Purpose; Group B, Syntac; Group C, All-Bond 2 and Scotchbond 2; Group D, Scotchbond 2 and Denthesive. In Group C, there was no significant difference between Scotchbond 2 and All-Bond 2. In Group D there was no significant difference between Scotchbond 2 and Denthesive, however, there was significant difference between All-Bond 2 and Denthesive. It was concluded that XR Bond and Scotchbond Multi-Purpose had significantly better shear bond strength than the other dentine adhesives. PMID- 8195483 TI - Clinical relevance of laboratory fatigue studies. AB - From a clinical point of view, fatigue in dental restorative resins is discussed by the way that fatigue expresses itself in different forms in these materials. In vitro testing of the fatigue sensitivity of dental composites is far from conclusive: there is a need for standardized testing methodology. Some findings obtained with a recently developed fatigue machine, and interpreted as a function of masticatory stresses, indicate that the generalized form of fatigue will probably be limited to microfilled based composites. PMID- 8195484 TI - Don't bank here. PMID- 8195485 TI - A myopic approach? PMID- 8195486 TI - Treating TMD. PMID- 8195487 TI - Sargenti defended. PMID- 8195488 TI - Quackery. PMID- 8195489 TI - A second opinion. PMID- 8195490 TI - Antibiotics can prevent implant failure. PMID- 8195491 TI - New shield protects oral tissues during radiation. PMID- 8195492 TI - Researchers agree on periodontitis-causing pathogens. PMID- 8195493 TI - A life in science. Interview by Daniel McCann. PMID- 8195494 TI - The good news of oral health. PMID- 8195495 TI - Trends in tooth loss among U.S. employed adults from 1971 to 1985. AB - A comparison of data from a 1971-74 study and a 1985-86 study is used to establish trends in tooth loss among adults. The data show that tooth retention among employed U.S. adults improved almost 15 percent in the decade between the two studies, and edentulism was almost cut in half. PMID- 8195496 TI - Caries-preventive effect of glass ionomer sealant reapplication: study presents three-year results. AB - The caries-preventive effect of glass-ionomer sealant depends on both retention of sealant and fluoride release. In this study, the retention rate was maintained by sealant reapplication over three years. Caries reduction was 76.1 percent at one year, 69.9 percent at two years and 66.5 percent at three years. Reapplication is an acceptable procedure and seemed to improve caries reduction. PMID- 8195497 TI - A program to help major league baseball players quit using spit tobacco. AB - There are few reports in the scientific literature that describe tested methods for helping people quit using spit (smokeless) tobacco. This paper reports data from a pilot study to determine the effectiveness of two dental-oriented interventions to promote cessation of ST use among major league baseball players. These preliminary findings suggest that interventions involving an oral examination and advice to quit, combined with behavioral counseling, may effectively decrease ST use among professional baseball players. PMID- 8195498 TI - Prevention of root surface caries using a dental adhesive. AB - Dental adhesives might be applied as sealants to exposed root surfaces to prevent root caries. One resin adhesive system significantly reduced the incidence and severity of lesions in an artificial caries system. PMID- 8195499 TI - Evaluating spatter and aerosol contamination during dental procedures. AB - A pilot study evaluated the distribution of spatter and aerosols generated by high-speed instrumentation. In the first phase, fluorescent dye was added to the handpiece water supply. In the second, blood agar culture plates were placed in the operatory. Results show that contamination from spatter and aerosol dissemination remains a significant hazard for dental personnel. PMID- 8195500 TI - After amalgam, what? Other materials fall short. PMID- 8195501 TI - Assessing the nicotine content of smokeless tobacco products. AB - The nicotine content of 11 popular brands of smokeless tobacco--including moist snuff, plug and loose-leaf chewing tobacco--was analyzed. In general, moist snuff has the highest nicotine content and loose-leaf chewing tobacco has the lowest, with plug tobacco falling in the middle. Variability in nicotine content may affect smokeless tobacco use and should be considered when studying usage as a variable for adverse effects of ST use. PMID- 8195502 TI - Retaining periodontally "hopeless" teeth. AB - A case of advanced periodontitis with many hopeless teeth, treated and maintained for 8-1/2 years, is presented. This case suggests a successful departure from traditional treatment. PMID- 8195503 TI - Radiographic protocol for patients needing antibiotic prophylaxis: dental schools report no consensus. AB - A survey of current U.S. and Canadian dental school policies shows different opinions about whether intraoral radiographs are invasive procedures and would require antibiotic prophylaxis before treatment. PMID- 8195504 TI - Diagnosing oral diseases that affect the eyes. AB - Dentists can often help diagnose diseases that affect the eyes. This article discusses the diseases and iatrogenic dental conditions where ophthalmic and oral findings play a key role in diagnosis and treatment. PMID- 8195505 TI - Now is the time to change to custom impression trays. PMID- 8195506 TI - Impact of quality assurance program: providing practice assessment. AB - Participation in a self-administered quality assessment (SAQA) program led to changes in New Jersey dentists' perceptions of practice quality. Ninety-four percent indicated they discovered practice deficiencies. This study suggests that using a self-administered quality assessment program, such as the SAQA program, can lead to a better understanding of a practice's strengths and weaknesses. PMID- 8195507 TI - Statute of limitations halts malpractice action. PMID- 8195508 TI - Clinical outcome of patients with malignant ventricular tachyarrhythmias and a multiprogrammable implantable cardioverter-defibrillator implanted with or without thoracotomy: an international multicenter study. PCD Investigator Group. AB - OBJECTIVES: The long-term efficacy and safety of a third-generation implantable cardioverter-defibrillator implanted with thoracotomy and nonthoracotomy lead systems was evaluated in a multicenter international study. BACKGROUND: The clinical impact of transvenous leads for nonthoracotomy implantation and pacing for bradyarrhythmias and tachyarrhythmias in implantable cardioverter defibrillator systems is not well defined. METHODS: The safety of the implantation procedure and clinical outcome of 1,221 patients with symptomatic and life-threatening ventricular tachyarrhythmias who underwent implantation of a third-generation cardioverter-defibrillator using either a thoracotomy approach with epicardial leads (616 patients) or a nonthoracotomy approach with endocardial leads (605 patients) in a nonrandomized manner was analyzed. The implantable cardioverter-defibrillator system permitted pacing, cardioversion, defibrillation, arrhythmia event memory and noninvasive tachycardia induction. RESULTS: Successful implantation of an endocardial lead system was achieved in 605 (88.2%) of 686 patients and an epicardial system in 614 (99.7%) of 616 (p < 0.05). Perioperative 30-day mortality rate was 0.8% (1.8% including crossovers) in endocardial implant recipients compared with 4.2% (p < 0.001) in epicardial implant recipients (3.6% without crossovers, p < 0.05, respectively). Implantation mortality risk was significantly lower for nonthoracotomy systems irrespective of left ventricular ejection fraction or New York Heart Association functional class. Pacing therapies prevented need for cardioversion or defibrillation shocks in 89% of all ventricular tachycardia episodes and were comparably effective for both lead systems. Total survival rate at 2 years was significantly higher in endocardial (87.6%) than epicardial (81.9%) lead recipients (p < 0.001). Elimination of perioperative mortality from the analysis demonstrated comparable survival in both groups (p > 0.2). CONCLUSIONS: Third generation cardioverter-defibrillators with monophasic waveforms can be successfully implanted with epicardial (99.7%) and endocardial (88.2%) lead systems. We conclude that endocardial leads should be the implant technique of first choice. Improved patient management and tolerance for device therapy is achieved with the addition of antitachycardia pacemaker capability in these systems. PMID- 8195509 TI - Oversensing during ventricular pacing in patients with a third-generation implantable cardioverter-defibrillator. AB - OBJECTIVES: The purpose of this study was to identify the causes of oversensing during ventricular pacing in patients with a third-generation implantable cardioverter-defibrillator. BACKGROUND: Third-generation implantable cardioverter defibrillators have the capability for bradycardia pacing as well as antitachycardia pacing and defibrillation. With the Ventritex Cadence Tiered Therapy Defibrillator System, the pulse generator sensitivity is increased during bradycardia pacing to prevent undersensing of an arrhythmia with small amplitude signals. METHODS: Records from 85 consecutive patients who underwent implantation of a Cadence device for treatment of ventricular tachyarrhythmias were reviewed. RESULTS: Four patients required continuous pacing for bradyarrhythmias. In three of these patients, ventricular pacing was accomplished using the bradycardia pacing feature of the Cadence device. All three experienced spurious device discharges or had aborted shocks for oversensing. Analysis of real-time and stored electrograms revealed intermittent high frequency, large amplitude noise in two patients and oversensing of maximally gained R and T waves in the remaining patient. No evidence of lead fracture was found in any patient. The problem was solved by implantation of a separate permanent pacemaker in two patients and was partially solved by reprogramming of the device in the remaining patient. CONCLUSIONS: Although the Cadence implantable cardioverter-defibrillator has the capability for ventricular pacing in patients with bradyarrhythmias, certain features of its automatic gain control circuit limit its utility in this instance. Oversensing occurs commonly, leading to device discharges or aborted shocks. Implantation of a separate permanent pacemaker may be required in patients who have a Cadence device for tachyarrhythmia control and who also need pacing for bradycardia. PMID- 8195510 TI - Impaired left atrial mechanical function after cardioversion: relation to the duration of atrial fibrillation. AB - OBJECTIVES: We hypothesized that the time course of the recovery of atrial systolic function may be related to the duration of atrial fibrillation before cardioversion and sought to study noninvasively the recovery of left atrial mechanical function utilizing serial transthoracic Doppler studies. BACKGROUND: Recovery of atrial mechanical function may be delayed for several weeks after successful cardioversion of atrial fibrillation to sinus rhythm. METHODS: After successful cardioversion, 60 patients with atrial fibrillation of brief (< or = 2 weeks, 17 patients), moderate (> 2 to 6 weeks, 22 patients) or prolonged (> 6 weeks, 21 patients) duration were followed up with serial transmitral pulsed Doppler echocardiography immediately (60 patients) and at 24 h (45 patients), 1 week (41 patients), 1 month (31 patients) and > 3 months (30 patients) after cardioversion. RESULTS: Atrial mechanical function is greater immediately and at 24 h and 1 week after cardioversion in patients with "brief" compared with "prolonged" atrial fibrillation. In all groups, atrial mechanical function increases over time, ultimately achieving similar levels. Full recovery of atrial mechanical function, however, is achieved within 24 h in patients with brief atrial fibrillation, within 1 week in patients with moderate-duration atrial fibrillation and within 1 month in patients with prolonged atrial fibrillation. CONCLUSIONS: Recovery of left atrial mechanical function is related to the duration of atrial fibrillation before cardioversion. These findings have important implications for assessing the early hemodynamic benefit of successful cardioversion. PMID- 8195511 TI - T wave alternans in idiopathic long QT syndrome. AB - OBJECTIVES: The study evaluates the association between T wave alternans and the risk of cardiac events (syncope, aborted cardiac arrest or cardiac death) in a large population of patients with idiopathic long QT syndrome. BACKGROUND: T wave alternans is an infrequently recorded electrocardiographic (ECG) finding in patients with delayed repolarization, and its clinical significance is not clear. METHODS: A total of 4,656 ECG recordings in 2,442 patients enrolled in the International Long QT Syndrome Registry were reviewed for episodes of T wave alternans. To determine the risk associated with T wave alternans, independent of corrected QT interval (QTc) duration, patients with T wave alternans were matched for QTc value (every 0.025 s1/2) to patients with long QT syndrome without T wave alternans. RESULTS: T wave alternans was identified in 30 patients (25 of whom had a QTc interval > 0.50 s1/2). A strong association between QTc prolongation and T wave alternans was observed (odds ratio 1.23 per 0.01-s1/2 unit increase in QTc, p < 0.0001). Conditional logistic regression analyses with adjustment for age, gender, status and QTc value revealed that T wave alternans did not make a significant independent contribution to the risk of cardiac events. The risk of experiencing a major cardiac event was primarily related to length of QTc. CONCLUSIONS: T wave alternans, a marker of electrical instability and regional heterogeneity of repolarization, identifies a high risk subset of patients with prolonged repolarization. Patients with T wave alternans have an increased risk of cardiac events, but this risk is primarily related to the magnitude of repolarization delay (QTc prolongation). T wave alternans does not make an independent contribution to the risk of cardiac events after adjustment for QTc length. PMID- 8195513 TI - Time for yet another QT correction algorithm? Bazett and beyond. PMID- 8195512 TI - Relation between QT intervals and heart rates from 40 to 120 beats/min in rest electrocardiograms of men and a simple method to adjust QT interval values. AB - OBJECTIVES: The aim of this study was to establish the relation between QT intervals and a wide range of rest heart rates in men. These data provided the basis of a simple method for adjusting the QT interval for heart rate. BACKGROUND: Earlier correction equations give conflicting results, especially at low and high heart rates. METHODS: The QT intervals were measured in 324 electrocardiograms of healthy young men. The sample was weighted for low and high heart rates. A curve relating QT intervals and heart rates from 40 to 120 beats/min was constructed. The QT interval at 60 beats/min was used as the reference value, and an adjusting nomogram for different heart rates was created. The reliabilities of the nomogram and three earlier QT correction equations were tested in the study group and in 396 middle-aged men. RESULTS: The nomogram method presented (QTNc = QT + correcting number) adjusted the QT interval most accurately over the whole range of heart rates on the basis of smallest mean squared residual values between measured and predicted QT intervals. The Fridericia formula (QTFc = QT/RR1/3) gave the best correction at low, but failed at high, heart rates. The linear regression equation (QTLc = QT + 0.154[1 - RR], Framingham Study) was reliable at normal, but failed at low and high, heart rates. The Bazett formula (QTc = QT/RR1/2) performed poorest at all heart rates. The relation between QT and RR intervals was determined by three linear regressions expressing the slopes 0.116 for heart rates < 60 beats/min, 0.156 for heart rates from 60 to 100 beats/min and 0.384 for heart rates > 100 beats/min. CONCLUSIONS: The QT-RR relation over a wide range of heart rates does not permit the use of one simple adjustment equation. A nomogram providing, for every heart rate, the number of milliseconds that the QT interval must be corrected gives excellent adjustment. PMID- 8195514 TI - Prediction of isolated first diagonal branch occlusion by 12-lead electrocardiography: ST segment shift in leads I and aVL. AB - OBJECTIVES: This study was performed to determine electrocardiographic (ECG) features that could distinguish first diagonal branch occlusion from left anterior descending coronary artery occlusion. BACKGROUND: The ECG findings associated with first diagonal branch obstruction have not previously been compared with those of left anterior descending coronary artery obstruction. METHODS: The ECG findings in 34 patients with isolated diagonal branch occlusion (group 9) were compared with those in 20 patients with occlusion at site 6 (group 6) and 20 with occlusion at site 7 (group 7), according to American Heart Association classification. This study had a power > 80% to detect a 50% difference between groups at a probability value of 0.05. RESULTS: ST segment elevation was observed in leads I and aVL for all group 9 patients, in 80% (p < 0.05) of group 6 patients for lead I and 90% for lead aVL and in 50% (p < 0.01) of group 7 patients for lead I and 55% (p < 0.01) for lead aVL. Similarly, there was a higher incidence of abnormal Q waves and inverted T waves in leads I and aVL in group 9 than in groups 6 and 7. In contrast, group 9 showed a significantly lower incidence of ST segment elevation (3.4%), abnormal Q waves (3.0%) and inverted T waves (0%) in lead V1 than group 6 (80%, 40% and 90%, respectively) and group 7 (75%, 60% and 70%, respectively) (p < 0.01 for each). Multivariate analysis revealed that abnormalities in leads I and aVL, combined with a normal lead V1 (and V6), provided good criteria for distinguishing isolated diagonal branch occlusion from left anterior descending coronary artery occlusion. CONCLUSIONS: Isolated diagonal branch occlusion more frequently caused ECG abnormalities in leads I and aVL and less frequently caused changes in the precordial leads compared with left anterior descending coronary artery obstruction, indicating that leads I and aVL represent myocardium perfused by the diagonal branch. PMID- 8195515 TI - Characterization of the relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture. AB - OBJECTIVES: The purpose of this study was to determine whether different components of human atherosclerotic plaques exposed to flowing blood resulted in different degrees of thrombus formation. BACKGROUND: It is likely that the nature of the substrate exposed after spontaneous or angioplasty-induced plaque rupture is one factor determining whether an unstable plaque proceeds rapidly to an occlusive thrombus or persists as a nonocclusive mural thrombus. Although observational data show that plaque rupture is a potent stimulus for thrombosis, and exposed collagen is suggested to have a predominant role in thrombosis, the relative thrombogenicity of different components of human atherosclerotic plaques is not well established. METHODS: We investigated thrombus formation on foam cell rich matrix (obtained from fatty streaks), collagen-rich matrix (from sclerotic plaques), collagen-poor matrix without cholesterol crystals (from fibrolipid plaques), atheromatous core with abundant cholesterol crystals (from atheromatous plaques) and segments of normal intima derived from human aortas at necropsy. Specimens were mounted in a tubular chamber placed within an ex vivo extracorporeal perfusion system and exposed to heparinized porcine blood (mean [+/- SEM] activated partial thromboplastin time ratio 1.5 +/- 0.04) for 5 min under high shear rate conditions (1,690 s-1). Thrombus was quantitated by measurement of indium-labeled platelets and morphometric analysis. Under similar conditions, substrates were perfused with heparinized human blood (2 IU/ml) in an in vitro system, and thrombus formation was similarly evaluated. RESULTS: Thrombus formation on atheromatous core was up to sixfold greater than that on other substrates, including collagen-rich matrix (p = 0.0001) in both heterologous and homologous systems. Although the atheromatous core had a more irregular exposed surface and thrombus formation tended to increase with increasing roughness, the atheromatous core remained the most thrombogenic substrate when the substrates were normalized by the degree of irregularity as defined by the roughness index (p = 0.002). CONCLUSIONS: The atheromatous core is the most thrombogenic component of human atherosclerotic plaques. Therefore, plaques with a large atheromatous core content are at high risk of leading to acute coronary syndromes after spontaneous or mechanically induced rupture because of the increased thrombogenicity of their content. PMID- 8195516 TI - Localized intramural drug delivery during balloon angioplasty using hydrogel coated balloons and pressure-augmented diffusion. AB - OBJECTIVES: This study was designed to assess the feasibility of using hydrogel coated balloons to deliver biologically active agents to the blood vessel wall. BACKGROUND: The local intramural delivery of therapeutic agents during balloon angioplasty has been proposed as an adjunctive technique for preventing early intracoronary thrombosis and late restenosis. METHODS: To assess the efficacy of delivery and depth of penetration in vitro, local delivery of horseradish peroxidase was performed in 40 porcine peripheral arteries, and delivery of fluoresceinated heparin was performed in 20 porcine peripheral arteries and 7 human atheromatous arteries. To determine the persistence of these agents in the vessel wall in vivo, horseradish peroxidase was delivered to 18 porcine peripheral arteries that were harvested at intervals of 45 min to 48 h. Fluoresceinated heparin was delivered to 22 porcine peripheral arteries, 14 with the use of a protective sleeve, harvested at intervals of 30 s to 24 h. RESULTS: In vitro agent delivery was successful in all specimens. The depth of penetration of horseradish peroxidase was directly related to both balloon pressure (p < 0.04) and duration of inflation (p < 0.01). In vivo peroxidase staining was evident at 45 and 90 min but not thereafter. With the use of a protective sleeve, heparin was present in all arteries harvested at 30 s, with marked dissipation at 1 and 24 h. Without a sleeve, no fluorescein staining was detected in any artery. With both agents, delivery occurred consistently over broad regions of the vessel wall that were free of architectural disruption. CONCLUSIONS: Hydrogel-coated balloons can deliver biologically active agents to the vessel wall without gross tissue disruption and may provide an atraumatic method for the local delivery of therapeutic agents during balloon angioplasty. PMID- 8195517 TI - Local delivery of a synthetic antithrombin with a hydrogel-coated angioplasty balloon catheter inhibits platelet-dependent thrombosis. AB - OBJECTIVES: This study evaluated the efficacy of local administration of an antithrombin agent with a hydrogel-coated percutaneous transluminal coronary angioplasty balloon catheter. BACKGROUND: Intravenous infusion of antithrombin compounds has been shown to inhibit platelet-dependent thrombosis. However, hemorrhage is a common side effect associated with the systemic administration of antithrombin compounds. METHODS: The potent, irreversible thrombin inhibitor D Phe-L-Pro-L-Arginyl chloromethyl ketone (PPACK) was used to inhibit thrombus formation in chronic porcine arteriovenous shunts. Platelet deposition was quantitated with gamma camera imaging of 111In-labeled platelets. RESULTS: Intravenous administration of PPACK in swine, in doses sufficient to maximally inhibit thrombus formation, was associated with prolongation of bleeding parameters. The inhibition of thrombosis associated with intravenous PPACK was dose related. The amount of intravenous PPACK necessary for maximal inhibition of thrombus formation for a period of 45 min was 16.9 mg. In contrast, local delivery of PPACK with a hydrogel-coated angioplasty balloon deployed at the site of the thrombus inhibited platelet deposition for at least 45 min after the balloon was removed. Using 3H-labeled PPACK, the calculated amount of PPACK delivered was 33.5 micrograms. There was no change in bleeding time or activated partial thromboplastin time when swine received an intravenous bolus greater than the total amount of PPACK adsorbed onto the balloon (70 micrograms). CONCLUSIONS: These results suggest that in this model, a hydrogel-coated coronary angioplasty balloon catheter can be used to deliver enough antithrombin agent to inhibit platelet-dependent thrombosis for at least 45 min at doses that are several orders of magnitude less than those required for systemic administration. In addition, local delivery can provide effective inhibition of thrombus formation without alteration of bleeding parameters. PMID- 8195518 TI - Influence of pacing-induced myocardial ischemia on left atrial regurgitant jet: a transesophageal echocardiographic study. AB - OBJECTIVES: We investigated the influence of pacing-induced myocardial ischemia on systolic regurgitant jet in the left atrium, using simultaneous transesophageal echocardiography and transesophageal atrial pacing. BACKGROUND: In vitro studies have shown that ischemia-induced mitral regurgitation may occur as a result of mitral leaflet malcoaptation or (global) left ventricular dysfunction. However, no transesophageal echocardiographic study has thus far been performed to demonstrate the mechanism and extent of mitral regurgitation during myocardial ischemia in patients. METHODS: In 24 patients (mean [+/- SD] age 57 +/- 10 years) with (15 patients) and without (9 control subjects) coronary artery disease, heart rate, blood pressure and systolic regurgitant jet were assessed before and immediately after pacing. Pacing was increased stepwise up to 160 beats/min to provoke wall motion abnormalities while the left ventricular short axis was monitored at the midpapillary muscle level. Other variables obtained before and at peak pacing included left ventricular end-diastolic and end-systolic areas and left ventricular end-diastolic and end-systolic endocardial segmental lengths. RESULTS: Heart rate and blood pressure before and after pacing were not significantly different in control subjects or in patients. At baseline, a jet was present in all but three control subjects. New or increased anterior or posterior wall motion abnormalities were observed during pacing in seven and eight patients, respectively. End-systolic left ventricular areas and segment lengths were significantly reduced in control subjects compared with patients with coronary artery disease at peak pacing (p < 0.05). The increase in systolic regurgitant jet was significantly greater in patients (2.0 +/- 1.1 to 3.1 +/- 1.8 cm2 vs. 0.7 +/- 0.7 to 0.9 +/- 0.9 cm2 [after pacing], p < 0.01). This effect was greater in patients with posterior than with anterior wall motion abnormalities (3.5 +/- 1.6 vs. 2.1 +/- 1.2 cm2 [after pacing], p < 0.05). CONCLUSIONS: Quantitative changes in geometry and function of the left ventricle caused by pacing-induced myocardial ischemia augments systolic regurgitant jet size. An increase in the jet during atrial pacing is associated with new or increased wall motion abnormalities, especially of the posterior wall. Pacing induced anterior wall motion abnormalities appear not to be related directly to an increase in the jet. PMID- 8195519 TI - Efficacy of spinal cord stimulation as adjuvant therapy for intractable angina pectoris: a prospective, randomized clinical study. Working Group on Neurocardiology. AB - OBJECTIVES: In a prospective, randomized study with an 8-week follow-up period, we evaluated the efficacy of spinal cord stimulation on exercise capacity and quality of life in patients with intractable angina. BACKGROUND: Despite important achievements in therapy for ischemic heart disease, there remain patients with intractable symptoms of angina. In uncontrolled observations, several investigators have reported beneficial effects of spinal cord stimulation as an additional therapy for patients with angina pectoris. METHODS: Seventeen patients were randomly assigned to the treatment (implantation within 2 weeks, eight patients) or control (implantation after 8 weeks, nine patients) group. Assessment of exercise capacity was performed by treadmill exercise testing. Quality of life was evaluated by daily and social activity scores and recording sublingual glyceryl trinitrate intake and angina pectoris attacks in a diary. After the 8-week study period, the control group also received the spinal cord stimulation device, and all patients were followed up for 12 months. RESULTS: The treatment but not the control group demonstrated a significant increase in exercise duration (p < 0.02), rate-pressure product (p < 0.03) and time to angina (p < 0.04), with a decrease in ST segment depression (p < 0.05). This was associated with an increase in daily life (p < 0.008) and social activity (p < 0.005) scores and a reduction in glyceryl trinitrate intake (p < 0.004) and episodes of angina pectoris (p < 0.003). During the 1-year follow-up, improvement in all quality of life variables was linear for the entire group compared with baseline. The time to angina, exercise duration and ST segment depression showed a second-order trend. CONCLUSIONS: Spinal cord stimulation significantly improves exercise capacity and quality of life. On the basis of an increase in exercise capacity and rate-pressure product, the mechanism by which spinal cord stimulation acts may be related to improved oxygen supply to the heart combined with an analgesic effect. PMID- 8195520 TI - Transesophageal echocardiography and carotid ultrasound in patients with cerebral ischemia: prevalence of findings and recurrent stroke risk. AB - OBJECTIVES: This study was conducted to determine the yield of transesophageal echocardiographic findings in a consecutive series of patients with stroke and transient ischemic attack, with and without carotid stenosis, and to estimate the recurrent stroke risk associated with specific echocardiographic findings. BACKGROUND: Transesophageal echocardiography has a high yield for identification of potential sources of cardiac embolism in patients with cerebral ischemia; however, the clinical significance of the most commonly detected abnormalities is uncertain. METHODS: We evaluated 145 consecutively admitted patients with stroke or transient ischemic attack with both transesophageal echocardiography and carotid ultrasound. Patients were followed up prospectively for a mean duration of 18 months to document the rate of recurrent cerebral ischemia. RESULTS: Transesophageal echocardiography detected at least one potential cardiac source of embolism in 45% of the patients. Atrial septal aneurysm and interatrial shunt were detected more frequently in patients who did not have a significant carotid stenosis that could account for their ischemic event. During follow-up, a higher rate of recurrent stroke or transient ischemic attack occurred in patients with positive transesophageal echocardiographic findings, particularly atrial septal aneurysm, interatrial shunt and left atrial thrombus. CONCLUSIONS: These data support recent studies that suggest that atrial septal aneurysm and interatrial shunts may be a significant source of cardioembolic stroke. Further studies are needed to clarify the optimal management of patients with these abnormalities. PMID- 8195521 TI - Percutaneous mitral balloon valvotomy in patients with calcific mitral stenosis: immediate and long-term outcome. AB - OBJECTIVES: This study analyzed the immediate and long-term outcome of percutaneous balloon mitral valvotomy in patients with and without fluoroscopically visible mitral valve calcification. BACKGROUND: Mitral valve calcification has been shown to be an important factor in determining immediate and long-term outcome of patients undergoing surgical mitral commissurotomy. Patient selection has an important impact on the outcome of percutaneous balloon mitral valvotomy. METHODS: The immediate and long-term results of percutaneous balloon mitral valvotomy were compared in 155 patients with and 173 patients without mitral valve calcification. The patients with calcified valves were assigned to four groups according to severity of calcification. RESULTS: Patients with calcified mitral stenosis more frequently were in New York Heart Association functional class III or IV and more frequently had atrial fibrillation, previous surgical commissurotomy, echocardiographic score > 8, higher pulmonary artery and left atrial pressures, higher pulmonary vascular resistance and mean mitral valve gradient and lower cardiac output and smaller mitral valve area. Mitral valve area after valvotomy was significantly smaller in patients with calcified valves (1.8 +/- 0.06 vs. 2.1 +/- 0.06 cm2) and was > or = 1.5 cm2 in 65% of patients with and 83% of patients without calcified valves (p = 0.004). A successful outcome, defined as mitral valve area > 1.5 cm2 without significant mitral regurgitation and left to right shunting, was achieved in 52% of patients with and 69% of patients without uncalcified valves (p = 0.001). The success rate was 59%, 48%, 35% and 33% in subgroups with 1+, 2+, 3+ and 4+ calcification, respectively. The rates of significant left to right shunting and mitral regurgitation after valvuloplasty were similar in the two groups. Estimated survival rate (80% vs. 99%, respectively, p = 0.0001), survival rate without mitral valve replacement (67% vs. 93%, respectively, p < 0.00005) and event-free survival rate (63% vs. 88%, respectively, p < 0.00005) at 2 years were significantly better in the patients with uncalcified valves. Survival rate curves became progressively worse as the severity of calcification increased. CONCLUSIONS: These findings indicate that immediate and long-term results of mitral valvuloplasty are not as successful in patients with fluoroscopically visible mitral valve calcification as in those without calcification. PMID- 8195522 TI - Improved hemodynamic function and mechanical efficiency in congestive heart failure with sodium dichloroacetate. AB - OBJECTIVES: The purpose of this study was to determine whether sodium dichloroacetate improves hemodynamic performance and mechanical efficiency in congestive heart failure. BACKGROUND: Congestive heart failure is associated with impaired hemodynamic performance and reduced mechanical efficiency. Dichloroacetate stimulates pyruvate dehydrogenase activity by inhibition of pyruvate dehydrogenase kinase, which results in inhibition of free fatty acid metabolism and stimulation of high respiratory quotient glucose and lactate consumption by the heart. Facilitation of glucose and lactate consumption with dichloroacetate should improve mechanical efficiency of the failing ventricle. METHODS: Ten patients with New York Heart Association functional class III to IV congestive heart failure were studied. Dichloroacetate (50 mg/kg body weight) was administered intravenously for 30 min, with measurements of hemodynamic variables, coronary sinus blood flow and blood gas, glucose and lactate levels for 2 h. The same patients were also given dobutamine (5 to 12.5 micrograms/kg per min) for comparison. RESULTS: Therapeutic levels of dichloroacetate were achieved (100 to 160 micrograms/liter of plasma). Myocardial consumption of lactate was stimulated from 29% to 37.4%. Forward stroke volumes increased (+5.3 ml/beat, p < 0.02), as did left ventricular stroke work (+1.8 g-m/m2 per beat, p < 0.02) and left ventricular minute work (from 1.38 to 1.55 kg-m/m2 per min, p < 0.01). Myocardial oxygen consumption decreased (from 19.3 to 16.5 ml/min, p = 0.06) as left ventricular minute work increased. Left ventricular mechanical efficiency thus improved from 15.2% to 20.6% (p = 0.03). Dobutamine administration resulted in the opposite trend with respect to myocardial lactate extraction (from 34% to 15.3%, p < 0.02). Stroke volume increased (+7.4 ml/beat, p = NS vs. dichloroacetate), as did left ventricular minute work (from 1.29 to 1.59 g-m/m2 per min, p < 0.01 vs. dichloroacetate) and myocardial oxygen consumption (from 18.6 to 21.0 ml/min, p = 0.06 vs. dichloroacetate). Left ventricular mechanical efficiency did not change with dobutamine administration (from 16.4% to 15.8%, p = NS). CONCLUSIONS: Dichloroacetate administration stimulates myocardial lactate consumption and improves left ventricular mechanical efficiency. Forward stroke volume and left ventricular minute work increase significantly, with a simultaneous reduction in myocardial oxygen consumption. Dobutamine administration results in similar hemodynamic improvements but with no change in left ventricular mechanical efficiency and with opposite effects on lactate metabolism. The opposing metabolic actions, yet similar hemodynamic responses, of dichloroacetate and dobutamine suggest that these agents may be complementary in the treatment of congestive heart failure. PMID- 8195523 TI - Pericardial effusions after cardiac transplantation. AB - OBJECTIVES: The aim of this study was to determine the etiologic factors in the formation of significant pericardial effusion after orthotopic heart transplantation and to determine the association of pericardial effusion with survival. BACKGROUND: The formation of pericardial effusions has been well described after orthotopic heart transplantation, but the risk factors for development of effusions remain unclear. Rejection and cyclosporine have been cited as possible causes, but anatomic factors have not been studied. METHODS: We conducted a retrospective review of medical records and echocardiograms of 203 consecutive patients at one center, including ischemic time, incidence and severity of rejection, weight difference between donor and recipient and previous cardiac surgical history. Multivariate analysis was performed, and actuarial survival rate curves were calculated according to the Kaplan-Meier method. RESULTS: Eighteen (8.9%) of 203 transplant recipients developed moderate to large pericardial effusions. Forty-four percent of patients required pericardiocentesis, and 28% subsequently required pericardiectomy for management of the effusions. Multivariate analysis identified the presence of a positive weight difference between recipient and donor (recipient weight > donor weight) and the lack of previous median sternotomy as the most powerful predictors of effusion formation. No significant association was found with rejection. There was no difference in actuarial survival rate between patients with and without effusions. CONCLUSIONS: A positive mismatch in weight between recipient and donor and the absence of previous cardiac surgery are associated with the formation of significant pericardial effusions. Closer monitoring of these patients at risk may be warranted. PMID- 8195524 TI - Doppler-derived mitral deceleration time of early filling as a strong predictor of pulmonary capillary wedge pressure in postinfarction patients with left ventricular systolic dysfunction. AB - OBJECTIVES: The aim of this study was to investigate the correlations between Doppler-derived transmitral flow velocity variables and pulmonary capillary wedge pressure in patients with severe left ventricular systolic dysfunction. BACKGROUND: Abnormal relaxation and increased chamber stiffness have opposing effects on the left ventricular filling pattern. When both abnormalities are present at the same time, as often occurs in patients with systolic dysfunction, the ability of Doppler recording to assess diastolic function and predict left ventricular filling pressure may be significantly compromised. METHOD: Pulmonary capillary wedge pressure and Doppler transmitral flow velocity profile were simultaneously recorded in 140 postinfarction patients with ejection fraction < or = 35%. RESULTS: Correlation between the ratio of mitral peak flow velocity in early diastole to peak flow velocity in late diastole (E/A ratio) and pulmonary capillary wedge pressure was weak (r = 0.65). Although the specificity of E/A > or = 2 in predicting > or = 20 mm Hg in pulmonary capillary wedge pressure was high (99%), its sensitivity was low (43%). Conversely, a very close negative correlation was found between mitral deceleration time of early filling and pulmonary capillary wedge pressure (r = -0.90). Sensitivity and specificity of < or = 120 ms in deceleration time in predicting > or = 20 mm Hg in pulmonary capillary wedge pressure were 100% and 99%, respectively. CONCLUSIONS: Doppler derived mitral deceleration time of early filling provides a simple and accurate means of estimating pulmonary capillary wedge pressure that is particularly useful in patients with a normal or normalized mitral flow velocity pattern. PMID- 8195525 TI - Validation of continuous wave Doppler-determined right ventricular peak positive and negative dP/dt: effect of right atrial pressure on measurement. AB - OBJECTIVES: The present study aimed to validate the peak positive and negative values of the first derivative of right ventricular pressure (dP/dt) using Doppler echocardiography and to determine the impact of right atrial pressure on the measurements. BACKGROUND: A pressure gradient between the right ventricle and the right atrium can be obtained by continuous wave Doppler-derived tricuspid regurgitant velocity using the simplified Bernoulli equation. If right atrial pressure fluctuation during systole and isovolumic diastole were small compared with right ventricular pressure changes, right ventricular pressure could be evaluated, and maximal positive and negative dP/dt could also be determined with Doppler echocardiography. METHODS: We investigated 11 patients with a wide range of right atrial pressure with tricuspid regurgitation using simultaneous examination by Doppler ultrasound and catheterization. Hemodynamic conditions were altered by the Valsalva maneuver, and a total of 40 beats were analyzed. RESULTS: There was good correlation between Doppler-derived and catheterization derived peak positive dP/dt (y = 1.0x - 15.4, r = 0.98, n = 40), irrespective of the level of right atrial pressure. Doppler-derived peak negative dP/dt also showed good correlation with that determined by catheterization (y = 0.9x + 58.2, r = 0.93, n = 40). However, in patients with high right atrial pressure (v wave pressure > or = 10 mm Hg), Doppler-derived peak negative dP/dt tended to show lower values than those from catheterization measurements, except in patients with pulmonary hypertension. CONCLUSIONS: We conclude that right ventricular dP/dt can be estimated by the Doppler method accurately and noninvasively. However, when right atrial pressure is relatively high compared with corresponding right ventricular pressure changes during isovolumic diastole, Doppler-derived peak negative dP/dt might underestimate catheter-derived measurements. PMID- 8195526 TI - Critical capillary oxygen partial pressure and lactate threshold in patients with cardiovascular disease. AB - OBJECTIVES: The aim of this study was to determine the relation between femoral vein oxygen partial pressure (PO2) and lactate increase during exercise in patients with cardiovascular disease. BACKGROUND: Considerable controversy surrounds the relation between the increase in lactate during exercise and the oxygen supply to the exercising muscles. We assumed that femoral vein PO2 would be a measure of end-capillary PO2 during leg-cycling exercise and that it would decrease to a "floor" level when the critical capillary PO2 (the PO2 below which the capillary-mitochondrial difference would be too low to allow oxygen consumption) was reached. At the critical capillary PO2, anaerobic metabolism should take place, and lactate should increase in the effluent blood. METHODS: Ten patients with cardiovascular disease performed two 6-min constant work rate tests (moderate and heavy intensity) and an incremental exercise test to the symptom-limited maximum on a cycle ergometer. Femoral vein blood was repeatedly sampled through a percutaneous catheter before and during each exercise test. RESULTS: The PO2 rapidly decreased toward a minimal value with increasing oxygen uptake for all three tests in all patients. After reaching its nadir (18.2 +/- 2.0 mm Hg), the PO2 remained unchanged in five patients but increased in the other five patients despite the further increase in work rate and oxygen uptake. The relation between PO2 and oxygen uptake was characteristic for each patient and independent of the protocol used for the study. Femoral vein lactate did not change appreciably until PO2 reached the minimal (critical) value. Thereafter, it dramatically increased without a further decrease in PO2. The minimal PO2 was positively correlated with the peak oxygen uptake (r = 0.70, p = 0.01). CONCLUSIONS: During leg-cycling exercise, muscle capillary PO2 reaches a minimal value in the midrange of the subjects' work capacity before lactate concentration increases in patients with cardiovascular disease. The lack of further decrease in PO2 at the oxygen uptake at which lactate starts to increase suggests that the minimal capillary PO2 is the "critical" capillary PO2. PMID- 8195527 TI - Follow-up of radiofrequency catheter ablation in children: results in 100 consecutive patients. AB - OBJECTIVES: The purpose of this study was to determine the outcome of a group of closely followed-up pediatric patients who had undergone radiofrequency ablation for cardiac arrhythmias. BACKGROUND: Although radiofrequency ablation in children has been shown to be effective and safe in the short term, results of longer term follow-up of these children must be considered when determining the place of radiofrequency ablation in the management of pediatric arrhythmias. METHODS: One hundred children aged 2 months to 17 years underwent a total of 119 radiofrequency ablation procedures for cure of tachycardia. Follow-up clinical data, electrocardiograms and 24-h Holter monitors were obtained and analyzed. RESULTS: All patients were alive, and none were lost to follow-up after a mean follow-up of 21.5 months (range 6 to 50). Success at last follow-up included accessory pathways in 66 (89%) of 74 patients, atrioventricular (AV) node reentry in 15 (88%) of 17, intraatrial reentry in 2 (67%) of 3, atrial flutter in 3 (100%) of 3, atrial ectopic tachycardia in 2 (67%) of 3, junctional ectopic tachycardia in 1 (100%) of 1 and ventricular tachycardia in 2 (100%) of 2 (overall success, 90 [90%] of 100). All recurrences were observed within 6 months of ablation. Major and minor complications (7%) included chest burn (one patient), foot microembolus (two patients), hematoma without pulse loss (four patients), femoral arteriovenous fistula requiring repair (one patient) and transient Mobitz I AV block (one patient). Immediate success, recurrence and complication rates were similar in the > or = 12-year old versus the < 12-year old group. Echocardiograms, available in 109 (92%) of 119 patients, showed possible procedure-related abnormalities in 2 (mitral regurgitation in 1, tricuspid regurgitation in 1, both mild), with no aortic insufficiency after 30 left-sided ablations performed by the retrograde approach. Follow-up Holter monitors, available in 77 (77%) of 100 patients, showed possible procedure related abnormalities in 5 (frequent atrial ectopic tachycardia in 2, atrial flutter in 1, accelerated ventricular rhythm in 2). There were no early or late deaths. CONCLUSIONS: In children, the risks of radiofrequency ablation are low at follow-up evaluation. Longer-term follow-up of children undergoing radiofrequency ablation will be necessary to determine whether coronary abnormalities or serious new arrhythmias will develop. PMID- 8195528 TI - Transesophageal echocardiographic guidance of transcatheter ventricular septal defect closure. AB - OBJECTIVES: This report describes transesophageal echocardiographic guidance of transcatheter closure of ventricular septal defects and its value as an adjunct to fluoroscopy and angiography in this procedure. BACKGROUND: Experience with transcatheter closure of ventricular septal defects has identified a diverse group of patients in whom it may be the procedure of choice. Although facilitating other interventional procedures, such as transcatheter closure of atrial septal defects, the value of transesophageal echocardiographic guidance for transcatheter ventricular septal defect closure has not been documented. METHODS: All patients who underwent ventricular septal defect closure with transesophageal echocardiographic guidance before November 1992 were included. Angiograms and echocardiograms were reviewed to evaluate device position and relation to valve tissue during placement and to assess residual flow after device implantation. The ability of transesophageal echocardiography to assess these variables was compared with fluoroscopy and angiography. RESULTS: Transesophageal echocardiographic guidance was used in 31 of the 83 catheterizations involving transcatheter ventricular septal defect closure performed between February 1990 and November 1992. Under transesophageal echocardiographic guidance, 45 devices were implanted: 23 in muscular ventricular septal defects, 17 in residual postoperative patch margin defects and 5 in other ventricular septal defects. Transesophageal echocardiographic guidance enhanced assessment of device position and proximity to valve structures and markedly improved assessment of residual flow. Assessment of residual flow with transesophageal echocardiography eliminated the need for multiple angiograms in some patients. Combining transesophageal echocardiography with fluoroscopy and angiography provided the most information. CONCLUSIONS: Transesophageal echocardiography facilitates transcatheter closure of ventricular septal defects by improving assessment of device position and effectiveness of closure. It is indicated when device placement is likely to be difficult or may interfere with valve structures or when multiple interventional procedures are anticipated. PMID- 8195529 TI - Transcatheter patent ductus arteriosus occlusion: application in the small child. AB - OBJECTIVES: This study intended to evaluate application of transcatheter occlusion of the patent ductus arteriosus in children < 10 kg body weight. BACKGROUND: Transcatheter occlusion of the patent ductus arteriosus in the child weighing > 10 kg has been proved safe and effective. METHODS: We reviewed 74 consecutive patients weighing < 10 kg (median 8.1 kg, range 3.98 to 10) and aged 4 to 30 months (median 13 months) who underwent patent ductus arteriosus occlusion between June 1986 and November 1992. A modification of the delivery system to facilitate application in small children is described. RESULTS: A 12-mm device was implanted in 50 patients and a 17-mm device in 24. Three device embolizations occurred early in the experience, and one required removal because of hemolysis associated with a moderate residual shunt. One 17-mm device was removed at catheterization because of acute compromise to left pulmonary artery flow after implantation. Prevalence of residual shunting was 33% at 6 months, 20% at 12 to 18 months and 17% at 2-year follow-up and was not related to device, age, weight or size of the patent ductus. Altered flow to the left pulmonary artery was noted in seven patients (9.9%), with more significant compromise associated with the 17-mm device. CONCLUSIONS: Transcatheter patent ductus arteriosus occlusion is feasible in the small child < 10 kg, particularly with the use of a modified delivery system. However, implantation of a 17-mm device in this patient population may impair flow to the left lung and should be reserved for the symptomatic child. PMID- 8195530 TI - Acute hemodynamic effects of adjustable atrial septal defect closure in the lateral tunnel Fontan procedure. AB - OBJECTIVES: This study evaluated the acute hemodynamic changes with atrial septal defect closure in the postoperative period in patients undergoing the Fontan procedure. BACKGROUND: The adjustable atrial septal defect is a modification of the Fontan procedure designed to improve cardiac output and reduce systemic venous hypertension during the postoperative period. Limited information is available on the effects of inter-atrial shunting on the physiology of direct cavopulmonary connection. METHODS: In 11 patients (aged 9 months to 14.5 years), the atrial septal defect was closed 8 h to 4.6 days (mean 1.7 days) postoperatively. Indications for closure included mean right atrial pressure < 15 mm Hg or arterial oxygen saturation < 80%, or both. RESULTS: Data presented are mean values +/- 1 SD. Mean right atrial pressure was 13.4 +/- 3.0 mm Hg on admission to the intensive care unit, 10.0 +/- 2.0 mm Hg (p = 0.02) immediately before closure and 11.4 +/- 2.8 mm Hg (p = 0.02) after closure. There was a significant decrease in cardiac output, as calculated from arteriovenous oxygen saturation difference (26 +/- 9%, p = 0.003), Doppler aortic flow (19 +/- 9%, p = 0.0002) and ventricular volumes by two-dimensional echocardiography (20 +/- 8%, p = 0.0001). Arterial oxygen saturation increased from 82 +/- 5% to 94 +/- 4% (p = 0.0001), and arteriovenous oxygen saturation difference increased from 25 +/- 8% to 33 +/- 9% (p = 0.0001). Systemic oxygen delivery decreased from 727 +/- 354 to 655 +/- 325 ml/min per m2 (p = 0.02). One patient required reopening of the atrial septal defect. CONCLUSIONS: These data demonstrate that a controlled right to left atrial shunt improves cardiac output and systemic oxygen delivery and facilitates the postoperative management of patients after the Fontan procedure. Atrial septal defect closure increases systemic saturation to normal values and prevents potential systemic embolization but significantly decreases oxygen delivery and might limit exercise tolerance. PMID- 8195531 TI - Clinical significance of maternal anti-Ro/SS-A antibodies in children with isolated heart block. AB - OBJECTIVES: We studied 30 consecutive children with isolated heart block to assess the clinical impact of the presence of maternal anti-Ro/SS-A antibodies for isolated heart block. BACKGROUND: Isolated heart block in children, often associated with maternal autoimmune disease leading to anti-Ro/SS-A auto-antibody production, is an infrequent but potentially lethal disorder. METHODS: Thirty children with isolated heart block were studied with respect to medical history and electrocardiographic (ECG) analysis. The presence of anti-Ro/SS-A antibodies was determined in the maternal serum. We also examined the ECGs of all brothers and sisters of the patients for conduction abnormalities. RESULTS: Twenty-one of the 30 children had an anti-Ro/SS-A-positive mother (group A); the other 9 children had an anti-Ro/SS-A-negative mother (group B). Comparison of the clinical data from both mothers and children revealed that these two groups differed significantly with respect to the following: Prenatal diagnosis and obstetric complications occurred more often in group A, whereas progression to complete block, QRS width > 0.08 s, premature ventricular contractions and ventricular standstills > 4.5 s occurred more often in group B. In addition, mothers of children in group A reported more spontaneous abortions. All siblings of children in groups A and B had normal ECGs, excluding a subclinical form of heart block. CONCLUSIONS: Two types of heart block can be recognized: Congenital heart block is associated with maternal anti-Ro/SS-A antibodies and numerous obstetric and neonatal complications. It is diagnosed prenatally or at birth and is usually complete at onset and probably has a substantial recurrence risk. Heart block that is acquired later in life is not associated with maternal autoimmunity and has no risk for recurrence. It often presents as a partial block but progresses to complete block in time. PMID- 8195532 TI - Intermediate follow-up of pediatric heart transplant recipients with elevated pulmonary vascular resistance index. AB - OBJECTIVES: This study examined perioperative and intermediate outcomes in pediatric cardiac transplant recipients who had elevated pulmonary vascular resistance indexes preoperatively. BACKGROUND: Elevated pulmonary vascular resistance was associated with poor outcome in previous studies and constitutes a relative contraindication to transplantation. Few studies have evaluated this poor outcome risk factor in pediatric patients. METHODS: To evaluate outcomes of nonneonatal transplant recipients, records were reviewed and divided into Group I (preoperative pulmonary vascular resistance index > or = 6 units.m2) and Group II (pulmonary vascular resistance index < 6 units.m2). Donor/recipient weight ratios, ischemic times, length of intensive care unit stay, posttransplantation infection rates, arrhythmia, response to pretransplantation vasodilator infusions and pulmonary vascular resistance indexes at the first and most recent posttransplantation biopsies were analyzed. RESULTS: Group I (8 patients) had a mean (+/- SEM) pulmonary vascular resistance index of 11.5 +/- 3.5 units,m2; Group II (29 patients) had a mean pulmonary vascular resistance index of 2.3 +/- 0.4 units,m2 (p < 0.002). Pulmonary vascular resistance index decreased from 12.3 +/- 3.9 to 3.9 +/- 0.9 units.m2 (p < 0.05) in 7 Group I patients undergoing vasodilator infusion during pretransplantation catheterization. Thirty-six orthotopic heart transplantations were performed and one heterotopic transplantation. Donor weights exceeded recipient weights by 13% and 31% for Groups I and II, respectively (p > 0.25). Donor ischemic time was 215 min for Group I and 225 min for Group II (p > 0.75). Intensive care unit stay was 11.5 days in Group I and 15.1 days in Group II (p = 0.20). Infection rate was 38% in both groups (p > 0.80). Arrhythmias occurred in 90% of Group I and 42% in Group II (p < 0.03) patients. Pulmonary resistance index in Group I decreased from 11.5 +/- 3.5 to 3.3 +/- 1.2 units.m2 (p < 0.03) by the first posttransplantation biopsy and have not changed subsequently. During 2.3 years (range 0.3 to 8.5) of follow-up, the mortality rate was 25% and 21% for Groups I and II, respectively (p > 0.80). CONCLUSIONS: Group I patients did not require significantly oversized donors, restricted donor locations or longer intensive care unit stays or have higher infection rates; however, arrhythmias were more frequent. Pulmonary resistance index normalized early after transplantation. Pulmonary vascular reactivity may be more important for survival than absolute resistance index. PMID- 8195533 TI - Use-dependent effects of lidocaine on the upper limit of vulnerability in open chest dogs. AB - OBJECTIVES: This study was performed to test the hypothesis that sodium channel activity is important in determining ventricular vulnerability to electric shocks. BACKGROUND: It is unknown whether sodium channel activity determines the upper limit of vulnerability. METHODS: The ventricles of 10 open chest dogs were paced at 300-, 500-, or 1,000-ms cycle lengths. The shock strength associated with a 50% probability of reaching the upper limit of vulnerability (ULV50) and the shock strength associated with a 50% probability of defibrillation (DFT50) were then determined by means of an up-down algorithm. Lidocaine (9.2-mg/kg body weight loading dose and 285-micrograms/kg per min maintenance dose) was then given, and the ULV50 and the DFT50 were redetermined after 1 h of stable infusion. RESULTS: The mean (+/- SD) lidocaine concentration was 11.9 +/- 2.4 micrograms/ml. At baseline, the ULV50 tested with each S1 cycle length was not significantly different from the DFT50. During lidocaine infusion, the ULV50 determined with cycle lengths of 300 and 500 ms (18.9 +/- 11.3 and 16.1 +/- 8.9 J, respectively) were significantly (p < 0.05) higher than those simultaneously determined for the DFT50 (11.2 +/- 4.1 and 10.9 +/- 5.6 J, respectively). However, when determined with an S1 cycle length of 1,000 ms, the ULV50 (10.4 +/- 4.1 J) was not found to be significantly different from the DFT50 (10.3 +/- 5.3 J). Lidocaine infusion increased (p < 0.05) QRS duration and the effective refractory periods for cycle lengths of 300 and 500 ms but not 1,000 ms. CONCLUSIONS: The effect of lidocaine on the upper limit of vulnerability is use dependent. These results are compatible with the hypothesis that sodium channel activity is important in determining ventricular vulnerability to electrical shocks. PMID- 8195534 TI - Imaging of cardiac neuronal function after cocaine exposure using carbon-11 hydroxyephedrine and positron emission tomography. AB - OBJECTIVES: The aim of the study was to define the effect of cocaine on the myocardial uptake and retention of C-11 hydroxyephedrine in the anesthetized dog model. BACKGROUND: Cardiac toxicity of cocaine has been linked to its inhibitory effect on norepinephrine reuptake by the sympathetic nerve terminals of the heart. Carbon-11 hydroxyephedrine is a C-11-labeled norepinephrine analog that has high specific affinity for uptake-1 and thus makes possible the assessment of the effect of cocaine on norepinephrine reuptake by cardiac sympathetic nerve terminals. METHODS: The cardiac kinetics of C-11 hydroxyephedrine as assessed by dynamic positron emission tomographic imaging were used to characterize norepinephrine reuptake by the sympathetic nerve terminals. Carbon-11 hydroxyephedrine was injected intravenously before, as well as at 5 min and 2.5 h after, intravenous administration of 2 mg/kg body weight of cocaine in anesthetized dogs. Hemodynamic variables and microsphere-determined cardiac blood flow were also measured before and after cocaine exposure. RESULTS: Intravenous injection of cocaine did not significantly affect hemodynamic variables and myocardial blood flow in the anesthetized animals. Compared with baseline, myocardial retention of C-11 hydroxyephedrine was significantly reduced by 78 +/- 3% (mean +/- SD) at 5 min and remained significantly reduced (28 +/- 17%) at 2.5 h after cocaine injection. Cocaine administration after C-11 hydroxyephedrine injection (30 min) resulted in rapid biexponential clearance of C-11 hydroxyephedrine from myocardium. CONCLUSIONS: These results suggest prolonged effects of cocaine on the sympathetic nerve terminals of the heart. Positron emission tomography provides a noninvasive and sensitive means to objectively assess the cardiac pharmacokinetics of drugs such as cocaine. PMID- 8195535 TI - Microwave balloon angioplasty effectively seals arterial dissections in an atherosclerotic rabbit model. AB - OBJECTIVES: The purpose of this study was to determine the effectiveness of microwave balloon angioplasty in sealing arterial dissections and to characterize the histologic features associated with this intervention. BACKGROUND: Coronary dissection accompanying balloon dilation is frequently associated with abrupt closure and acute ischemic complications. Effective management of this complication remains an active area of investigation. Because thermal energy is effective in welding separated atherosclerotic plaques, a microwave-based catheter system that provides controlled local heating was utilized in vessels with angioplasty-induced dissections. METHODS: Iliac artery dissections were induced in ahypercholesterolemic rabbit model. Vessels were randomly assigned to treatment with standard balloon angioplasty (control vessels) or microwave balloon angioplasty using an average temperature of 80 degrees C. The response of the artery was assessed angiographically and histologically. RESULTS: Angiographic success, defined as a reduction of dissection length by > 50% or the resolution of lumen haziness, was achieved in 63% of microwave-treated vessels and in 16% of control vessels (p < 0.005). Dissection length (mean +/- SD) was reduced 8.0 +/- 4.8 mm in microwave-treated vessels compared with 0.1 +/- 7.9 mm in vessels receiving standard balloon inflations (p < 0.005). Cellular necrosis was more commonly observed in microwave-treated vessels than in control vessels (73% vs. 17%, p < 0.05), but less intraluminal thrombus was seen in vessels exposed to microwave energy (p < 0.05). CONCLUSIONS: Microwave balloon angioplasty is more effective than routine balloon inflations in sealing arterial dissections in this model and appears to be less thrombogenic in these markedly disrupted vessels. PMID- 8195536 TI - Aminophylline fails to improve the outcome of cardiopulmonary resuscitation from prolonged ventricular fibrillation: a placebo-controlled, randomized, blinded experimental study. AB - OBJECTIVES: The purpose of this study was to evaluate systematically the effects of the adenosine antagonist aminophylline on resuscitation outcome in a canine model of postcardioversion nonperfusing rhythm. BACKGROUND: Theoretic considerations and experimental studies indicate that myocardial adenosine accumulation during prolonged ventricular fibrillation might play a significant role in postcardioversion asystole and electromechanical dissociation. A recent uncontrolled clinical trial has suggested that the adenosine antagonist aminophylline might improve the outcome of cardiopulmonary resuscitation from refractory bradyasystolic cardiac arrest. METHODS: Two placebo-controlled, randomized, blinded experimental studies were performed. In protocol 1 (20 dogs), ventricular fibrillation was induced and maintained for 7.5 min. Sixty seconds before cardioversion, dogs received 1 mg of epinephrine followed by 250 mg of aminophylline or placebo. In protocol 2 (20 dogs), dogs were cardioverted to electromechanical dissociation after 5 min of unsupported ventricular fibrillation. Sixty seconds later, all dogs received 1 mg of epinephrine followed by 250 mg of aminophylline or placebo. In both experiments, resuscitation efforts were continued until return of spontaneous circulation, or up to 30 min. The primary end point was survival to 1 h. RESULTS: In protocol 1, 4 of 10 dogs survived in the aminophylline group, whereas 7 of 10 dogs survived in the placebo group, a nonsignificant trend toward unfavorable outcome from aminophylline. Pretreatment with aminophylline increased the number of cardioversion applications required to terminate ventricular fibrillation. In protocol 2, 5 of 10 and 6 of 10 dogs survived in the aminophylline and placebo groups, respectively. CONCLUSIONS: The results of this study suggest that aminophylline fails to improve the outcome of resuscitation from prolonged ventricular fibrillation. It does not reverse established electromechanical dissociation and may in fact increase the number of cardioversion applications required to terminate ventricular fibrillation. The rationale for conducting clinical trials with aminophylline during cardiopulmonary resuscitation is questionable. PMID- 8195537 TI - Three-dimensional echocardiography: in vivo validation for right ventricular free wall mass as an index of hypertrophy. AB - OBJECTIVES: This study tested the ability of three-dimensional echocardiography to reconstruct the right ventricular free wall and determine its mass in vivo using a system that automatically combines two-dimensional images with their spatial locations. BACKGROUND: Right ventricular free wall thickness is limited as an index of right ventricular hypertrophy because right ventricular mass may increase by dilation without increased thickness and because trabeculations and oblique views can exaggerate thickness in individual M-mode and two-dimensional scans. Three-dimensional echocardiography may have potential advantages because it can integrate the entire free wall mass, uninfluenced by oblique views or geometric assumptions. METHODS: The three-dimensional system was applied to 12 beating canine hearts to reconstruct the right ventricular free wall in intersecting views. The corresponding mass was compared with actual weights of the excised right ventricular free wall (15.5 to 78 g). For comparison, right ventricular sinus and outflow tract thickness were also measured by two dimensional echocardiography, and the ability to predict mass from these values was determined. RESULTS: The three-dimensional algorithm successfully reproduced right ventricular free wall mass, which agreed well with actual values: y = 1.04x + 0.02, r = 0.985, SEE = 2.7 g (5.7% of the mean value). The two-dimensional predictions showed increased scatter: The variance of mass estimation, based on thickness, was 9.5 to 12.5 (average 11) times higher than the three-dimensional method (p < 0.02). CONCLUSIONS: Despite the irregular crescentic shape of the right ventricle, its free wall mass can be accurately measured by three dimensional echocardiography in vivo, providing closer agreement with actual mass than predictions based on wall thickness. This method, with the increased efficiency of the three-dimensional system, can potentially improve our ability to evaluate the presence and progression of right ventricular hypertrophy. PMID- 8195538 TI - Guidelines for physician training in advanced cardiac procedures: the importance of case mix. AB - In recent years, guidelines have been issued for the standardization of physician training in various advanced cardiac procedures. One area that is often neglected by guidelines committees is the need for an adequate case mix during physician training. Case mix refers to the variety of patients and diseases that the trainee is exposed to during the course of learning a new procedure. Although physicians may perform the requisite number of procedures during their training, if the case mix is inadequate, the physician's competence in performing the procedure and interpreting its results may be inadequate as well. PMID- 8195539 TI - Has Madison Avenue become medicine avenue? PMID- 8195540 TI - Technique of balloon pulmonary valvuloplasty in the neonate. PMID- 8195541 TI - Prediction of reocclusion after coronary thrombolysis. PMID- 8195542 TI - Opportunities in the nutrition and food sciences: research challenges and the next generation of investigators. PMID- 8195543 TI - Hurricanes and floods--a look at how RDs survive disasters. PMID- 8195544 TI - Surviving when the world falls apart. ADA members' skill, dedication, and teamwork triumph over devastation of California's earthquake. PMID- 8195545 TI - ADA supports efforts to reduce osteoporosis risk and recommends improvements for child nutrition programs. PMID- 8195546 TI - Health quackery: our role as professionals. PMID- 8195547 TI - Dietary fat, sugar, and fiber predict body fat content. AB - OBJECTIVE: This study was conducted to determine the relationships among the specific components of dietary fat and carbohydrate and body fatness in lean and obese adults. DESIGN: Body composition determination was performed on each subject by hydrostatic weighing at residual volume. Subsequently, the individual components of dietary fat and carbohydrate were examined relative to body fatness using a 3-day food diary and a food frequency questionnaire. SUBJECTS: Subjects were 23 lean (11.1 +/- 2.9% body fat) men, 23 obese (29.2 +/- 3.8% body fat) men, 17 lean (16.7 +/- 3.3% body fat) women, and 15 obese (42.7 +/- 3.9% body fat) women who volunteered for free diet and body composition analyses. Inclusion criteria were 15% body fat for lean men, 25% for obese men, 20% for lean women, and 35% for obese women. STATISTICAL ANALYSIS PERFORMED: Group comparisons for dietary variables were made with a multivariate analysis of variance. RESULTS: No differences were found between lean and obese subjects for energy intake or total sugar intake, but obese subjects derived a greater portion of their energy from fat (33.1 +/- 2.6% and 36.3 +/- 2.3% for obese men and women, respectively, vs 29.1 +/- 1.3% and 29.6 +/- 2.0%, lean men and women, respectively). Percent of fat intake for saturated, monounsaturated, and polyunsaturated fats was not different among groups. Obese subjects derived a greater percentage of their sugar intake from added sugars than lean subjects (38.0 +/- 3.5% vs 25.2 +/- 2.0%, respectively, for men; 47.9 +/- 8.0% vs 31.4 +/- 3.4%, respectively, for women). Dietary fiber was lower for obese men (20.9 +/- 1.8 g) and women (15.7 +/ 1.1 g) than for lean men (27.0 +/- 1.8 g) and women (22.7 +/- 2.1 g). APPLICATIONS/CONCLUSIONS: Obesity is maintained primarily by a diet that is high in fat and added sugar and relatively low in fiber. Alterations in diet composition rather than energy intake may be a weight control strategy for overweight adults. PMID- 8195548 TI - Short-term response to dietary counseling of hyperlipidemic outpatients of a lipid clinic. AB - OBJECTIVE: To evaluate the efficacy of a limited dietary intervention delivered by dietitians in a single counseling session on plasma lipid levels in free living subjects with hyperlipidemia. DESIGN: A 2-month, nonrandomized comparative study of dietary counseling efficacy in subjects with hyperlipidemia. Dietary instruction was conducted in a lipid clinic by dietitians. Subjects were instructed to follow a diet low in saturated fat and cholesterol (National Education Cholesterol Program step 1 or 2 diets) for 2 months with concomitant energy restriction for weight reduction when necessary. Another group of patients who did not receive dietary counseling during the same period served as a control. SUBJECTS: Ambulatory patients were recruited from the Lipid Clinic of the Montreal Clinical Research Institute. INTERVENTION: Dietary counseling was provided to 104 subjects with hypercholesterolemia and 113 subjects with hypertriglyceridemia. They were compared with 72 subjects with hypercholesterolemia and 80 subjects with hypertriglyceridemia who did not receive dietary counseling. RESULTS: In the hypercholesterolemic group, significant reductions in plasma cholesterol (mean +/- standard deviation = -5.7 +/- 11.7%) and low-density lipoprotein cholesterol (LDL-C) (-7.3 +/- 14.2%) and no changes in plasma very-low-density lipoprotein cholesterol (VLDL-C) or high density lipoprotein cholesterol (HDL-C) were observed after dietary counseling. The LDL-C response to diet was normally distributed, and 20% of the individuals with hypercholesterolemia reached LDL-C levels below 4.1 mmol/L. In patients with hypercholesterolemia and no clinical evidence of familial hypercholesterolemia, (n = 76) the reductions in plasma cholesterol (-6.6 +/- 10.8%) and LDL-C (-8.2 +/ 14%) were more pronounced. Among the latter patients, 27.6% reached LDL-C levels below 4.1 mmol/L. In subjects with hypertriglyceridemia, the reductions in plasma cholesterol (-4.8 +/- 12.8%), triglycerides (-20.7 +/- 33%), and VLDL-C (-19.5 +/ 29%) were associated with an increase in LDL-C (+8.5 +/- 25.7%) and HDL-C (+5.5 +/- 18%). Of the subjects with hypertriglyceridemia, 20% had triglyceride levels below 2.3 mmol/L after treatment. No significant changes were observed in the control groups during the same period. CONCLUSIONS: Dietary counseling of subjects with hypercholesterolemia or hypertriglyceridemia was associated with beneficial changes in plasma lipid levels after 2 months of dietary intervention. However, longer and more controlled dietary interventions are necessary for most patients to achieve lipid goals. PMID- 8195549 TI - Reading skill and comprehension of the dietary guidelines by WIC participants. AB - OBJECTIVE: The purpose of this study was to examine the match between reading skills and comprehension of the 1990 Dietary Guidelines in a Special Supplemental Food Program for Women, Infants, and Children (WIC) group (n = 32) compared with a non-WIC group and to determine which selected factors affected cloze scores. SUBJECTS/SAMPLES: The WIC group consisted of volunteers from WIC voucher pick-up sites, and the non-WIC group comprised women who met the qualification criteria for WIC, except income. METHODS: Reading skills were assessed using the Wide Range Achievement Test-Revised Level II (WRAT-R). Comprehension skills were measured using the cloze technique. MATERIALS: The introductory section of the Dietary Guidelines, originally written at the 10th-grade level, was simplified to the 7th-grade level for comprehension comparison. RESULTS: The WIC group had a significantly (P < .001) lower reading skill (WRAT-R score = 60.1; 11th-grade level) than the non-WIC group (WRAT-R score = 70.8; college level). Cloze scores from all subjects tested at the 10th-grade level indicated that 75% (n = 24) would be frustrated or need instructional assistance to understand the Dietary Guidelines. Simplification contributed to higher cloze scores. The WRAT-R score was one factor that significantly affected the cloze score (P < .001). Both education level and WRAT-R scores varied significantly between groups; however, analysis of covariance revealed that the effects were identical within both groups. IMPLICATIONS: WRAT-R can be used as a quick screening method for reading skill level of individuals in WIC programs and other counseling situations. The cloze techniques may be useful for assessing comprehension of specific printed materials. Assessment of reading skill and comprehension by nutrition educators is recommended to increase the likelihood of selecting and/or developing effective materials. PMID- 8195550 TI - Comparative advantage of 3-day food records over 24-hour recall and 5-day food frequency validated by observation of 9- and 10-year-old girls. AB - OBJECTIVE: The validity of the 24-hour recall, 3-day food record, and 5-day food frequency was assessed to decide on a dietary assessment method for the National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study. DESIGN: All subjects were assigned to one of three dietary assessment methods. Unobtrusive observers recorded types and amounts of foods eaten during lunch, and these were compared with the foods reported by the girls in the study. SETTING: School lunchrooms in California and Ohio. SUBJECTS: 58 girls, aged 9 and 10 years. MAIN OUTCOME MEASURES: Reporting errors for dietary assessment methods. STATISTICAL ANALYSES PERFORMED: Descriptive statistics, matched pair t tests, and Spearman correlation coefficients. RESULTS: Comparison of the intakes of energy and selected macronutrients showed different ranges of, and median percentage absolute errors for, each dietary assessment method. Percentage absolute errors ranged between 20 and 33 for the 5-day food frequency method; 19 and 39 for the 24-hour recall; and 12 and 22 for the 3-day food record. The proportion of missing foods (ie, observed food items not reported) and phantom foods (ie, reported food items not observed) by each method were 46% and 40%, respectively, for the 5-day food frequency; 30% and 33%, respectively, for the 24-hour recall; and 25% and 10%, respectively, for the 3-day food record. APPLICATIONS/CONCLUSIONS: Errors in food reporting and quantification can vary with the type of dietary methodology. Agreement between observed and reported intakes from 3-day food records made it the best overall choice. On this basis, it was selected as the method of assessment for the NHLBI Growth and Health Study. PMID- 8195551 TI - Food-related coping strategies after Hurricane Andrew. AB - This telephone survey examined food-related coping strategies in Floridian households after Hurricane Andrew. Approximately 137 households of university faculty and staff who lived in hurricane-damaged areas were interviewed. The average respondent was a college-educated woman between 41 and 60 years old. Prevailing food-purchasing problems included food stores that were either closed, without perishable food, distant, or crowded. In the absence of electricity and water, changes in food preparation included preparation of meals without a stove, more frequent use of grills and canned food, simpler meals, and less cooking. Changes in kitchen cleanup included using more disposables, cleaning more often, washing dishes by hand, and cleaning up less often because of damage in the kitchen. Respondents indicated that the hurricane experience taught them that they should have acquired more general supplies (eg, coolers, thermoses, propane stoves, and gas burners), more water and ice, and more nonperishable foods before the hurricane. PMID- 8195552 TI - Review of 5 years of a combined dietary and physical fitness intervention for control of serum cholesterol. AB - A chart review covering the first 5 years of clinical experience with a combined dietary and exercise intervention program for the reduction of hypercholesterolemia at the National Aeronautics and Space Administration headquarters demonstrated the program's success in maintaining high-density lipoprotein cholesterol (HDL-C) levels while significantly lowering total serum cholesterol levels. This combined program also resulted in improved ratios of total serum cholesterol to HDL-C and lowered levels of low-density lipoprotein cholesterol, thus further reducing the risk for cardiovascular disease. The National Aeronautics and Space Administration Cardiovascular Risk Reduction Program was developed after it was determined that although dietary intervention alone improved total cholesterol levels, it often resulted in a more than proportionate decrease in HDL-C and a worsening of the ratio of cholesterol to HDL-C. An approach was needed that would positively affect all factors of the lipid profile. The findings from the program indicate that reduction of cardiovascular risk can be accomplished easily and effectively at the worksite through dietary intervention, personal monitoring, and a reasonable exercise program. PMID- 8195553 TI - Is adipose tissue oversold as a health risk? AB - A high percentage of body fat is considered to be the primary cause of risks associated with high body weight. Yet body fat content per se may not cause the risks. The contribution of obesity to risks may be because overfilled adipose tissue cannot remove offending substances from circulation. The ability to remove excess glucose, lipids, and offending materials from circulation, not the amount of body fat, may be the important factor. People with large, partially filled adipose depots may have less risk than people with small, but filled adipose depots. This concept is supported by many studies. Energy restriction in genetically obese animals greatly increases longevity and slows signs of aging even while the animals remain obese. Weight reduction often corrects weight associated medical problems in obese persons without returning body-fat levels to normal. Statistically generated desirable body-fat contents or desirable height weight tables may have little meaning for individuals and may cause more harm than good. Because these standards are not appropriate for some people, they should be discarded as a guide for all. More emphasis should be placed on healthy lifestyles and less on body-fat percentages. PMID- 8195554 TI - Masking foods for food challenge: practical aspects of masking foods for a double blind, placebo-controlled food challenge. AB - In diagnosing a food allergy or food intolerance, a double-blind, placebo controlled food challenge (DBPCFC) with the suspected food or food substance is the only method available for objective confirmation of an assumed relationship between a suspected agent and a complaint. When the use of capsules as a vehicle for DBPCFC with the suspected agent is not feasible, recipes have to be developed for masking the suspected food with another food. We describe demands and other aspects of the development of recipes for DBPCFC purposes. The taste, smell, color, and texture of the suspected agent have to be hidden in such a way that the patient cannot tell which of the two foods (the active food or the placebo food) contains the suspected agent. Once developed, the recipes have to be judged carefully to ensure that the foods do not contain ingredients other than the suspected agent that can possibly provoke complaints in the patient. Besides ordinary equipment such as cutlery, glasses, and dishes, the minimal equipment needed for preparing the recipes is an accurate balance. The more laborious a recipe is to make, the more equipment is needed. The development of recipes and the preparation of masked foods are time-consuming, which makes DBPCFC with masked foods difficult to perform in daily clinical practice. Performing a DBPCFC with masked foods in daily clinical practice can be a great challenge to the imagination and creativity of a dietitian. PMID- 8195555 TI - Dietitians take the lead in diagnosis-related group coding. PMID- 8195556 TI - Registered dietitians as problem-based learning facilitators in a nutrition curriculum for freshmen medical students. PMID- 8195557 TI - Nutrition in nursing education and beginning practice. PMID- 8195558 TI - Counseling the athlete with an eating disorder: a case study. PMID- 8195559 TI - Educating high-risk Minnesotans about dietary fats, blood cholesterol, and heart disease. PMID- 8195560 TI - Positions of the American Dietetic Association: enrichment and fortification of foods and dietary supplements. PMID- 8195561 TI - Position of the American Dietetic Association: nutrition monitoring of the home parenteral and enteral patient. PMID- 8195562 TI - President's page: the challenge of change--protecting our future. PMID- 8195563 TI - Osteoporosis: visions for care and prevention--a conference report. AB - Osteoporosis, a bone-thinning disease that leads to fractures, affects 25 million Americans, mostly women. The good news is that this disease is preventable and treatable. Adequate nutrition, for example, is estimated to reduce the impact of osteoporosis by as much as one half. The bad news is that unless more attention is given to communicating preventive strategies, osteoporosis and its related costs will continue to escalate. To make osteoporosis a priority among health professionals and communicators, The American Dietetic Association, in cooperation with National Diary Council, held a conference on this subject in November 1993. Recognized national experts addressed the issue of osteoporosis from various perspectives. This article summarizes the information presented at this conference. Prevention of osteoporosis focuses on increasing peak bone mass, which is usually reached between the age of 30 to 35 years, and reducing bone loss in later years. Bone health is influenced by three major interacting factors: diet, exercise, and estrogen. To optimize bone health, accumulating scientific findings support intakes of calcium and vitamin D exceeding current Recommended Dietary Allowances (RDAs) for these nutrients. Unfortunately, most women in the United States, in particular female adolescents, do not consume the RDA for calcium. Although recommendations to prevent osteoporosis can be made, there are several obstacles to translating these recommendations into action. Examples include failure to inspire people to make lifestyle changes early in life and to provide understandable recommendations. To be facilitators of change and not just nutrition experts, dietitians and other health professionals need to overcome these obstacles and to effectively market the risks of and prevention strategies for osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195564 TI - A nursing challenge: Assessment and management of agitation in Alzheimer's patients. AB - 1. Agitation in patients with Alzheimer's disease is a pervasive problem. The behaviors associated with agitation may have detrimental effects on the patient, health care providers, and other patients. 2. Management of these behaviors is particularly challenging and, at times, frustrating for nursing personnel. 3. Attempts to identify the causative factors are essential to the development of an individualized plan of care. PMID- 8195565 TI - Chronic dementia. Challenges in feeding a patient. AB - 1. For the SDAT/MID patient, the nurse must determine food preferences and ability to eat, meet nutritional needs, and have a basic understanding of what techniques might assist professional and family caregivers with appropriate feeding techniques. 2. Ensuring adequate nutrition requires a multidisciplinary approach. Nurses must collaborate with dietitians and other health care professionals regarding food selection, feeding techniques, and environmental management that maximize nutritional outcomes. 3. There is a need for continuing research into nutritional needs and dietary interventions for dementia patients in all stages of illness and in all settings. PMID- 8195566 TI - Care of Alzheimer's patients: the paradigm shifts ... again. PMID- 8195567 TI - Legal aspects of nursing documentation for the Alzheimer's patient. AB - 1. Bergerson (1988) developed a set of charting rules called the FACT system (charting that is Factual, Accurate, Complete, and Timely). Nurses' notes are viewed as legal sources of documentation. 2. Nurse's notes made regarding the patient's cognitive status, ability to communicate and participate in treatment decisions, and safety needs may be carefully reviewed by the court system for a variety of reasons. 3. Nurses caring for patients with Alzheimer's disease must recognize that the primary function of any charting or documentation is optimal care for the individual patient. Nurses should not chart in anticipation of a legal review of the charting. However, nurses also must be aware that a legal challenge may prompt a review of the record and require the nurse to explain or clarify entries that have been made. PMID- 8195568 TI - Research trends in Alzheimer's disease. AB - Alzheimer's disease (AD) is a tragic condition. The individual experiencing the loss of memory, difficulty with language, change in personality, and disturbance in behavior associated with AD is not alone; the number of people with AD is estimated at 4 million; by the year 2050, as many as 14 million Americans may be afflicted (National Institute of Aging, 1992). AD is the fourth leading cause of death for adults, taking more than 100,000 lives annually. The families of these patients also are victims, as they watch their loved ones slowly forget them and all that was once meaningful in their lives. PMID- 8195569 TI - Special care units: meeting the needs of cognitively impaired persons. AB - 1. Alzheimer's disease (AD) is the fourth leading cause of death of older persons. Families frequently turn to nursing homes to provide the care that they are unable to provide during the later stages of the disease. 2. Sloane and Mathew concluded that special care units resulted in better care based on appearance, little difference in weight loss, similar range of services to traditional units, higher amount of interaction with residents more often out of their room, greater mobility, fewer medications, less physical restraint, and similar use of chemical restraints. 3. Alzheimer's disease does not affect an individual only; it affects a family. Effective programming includes the family. From the initial contact with the institution through placement on the special care unit--and often beyond the death of the resident--families are supported by the staff. PMID- 8195570 TI - Write right! PMID- 8195571 TI - Lessons from the Tao for birthing practice. AB - The metaphysics of the Tao Te Ching, as the basic structure of the universe, is used to examine birthing as creation. Lessons from the Tao regarding cultivating naturalness are drawn upon to provide suggestions for women in preparation for birthing, as well as for the nurses and midwives who attend them. Compatibility of this metaphysical view of birthing with Rogers's and Newman's nursing theories is identified, and the importance of honoring the metaphysical and spiritual aspects of birthing in nursing practice is stressed. PMID- 8195572 TI - Interactive guided imagery with oncology patients. A case illustration. AB - The technique of interactive guided imagery has numerous applications in the practice of oncology nursing: relaxation, pain and symptom management, grief work, and helping patients discern meaning in their illness experience, to name a few. The technique is described according to the theoretical framework presented by Roberto Assagioli. A case illustration demonstrates the application of the technique and is processed for its implications for nursing practice. A description of an in-service series for staff nurses interested in learning guided imagery is presented. PMID- 8195573 TI - Parish nursing--a conceptual framework. AB - Parish nursing is a current nursing care delivery model that practices holistic health care. Parish nurses provide care to a faith community, emphasizing the relationship between faith and health. Specific nursing activities address physical, emotional, and spiritual health and well-being, closely attending to the inseparability of these dimensions. Parish nurses may assume one or more roles associated with this practice to accomplish parish nursing activities and achieve the holistic health and well-being of individuals, families, and groups within the faith community. The five broad categories of client, health, nurse, environment, and nursing process provide a framework for organizing the concept of parish nursing for future nursing theory, research, and practice. PMID- 8195574 TI - An evaluation of the treatment effectiveness of the Chicago Health Outreach Acupuncture Clinic. AB - Acupuncture is a treatment modality that is particularly applicable for homeless clients because of its low cost and portability as well as because of its effectiveness in treating the symptomatology of pain syndromes, substance abuse, and human immunodeficiency virus infection. A two-part descriptive study was conducted to determine the response to acupuncture of homeless persons at the Chicago Health Outreach Clinic. Part 1 of the study consisted of a retrospective chart review of 45 patients to assess acupuncture treatment effectiveness. Part 2 of the study consisted of using a numerical rating scale report form to assess treatment effectiveness of 30 patients. Part 1 of the study indicated that 51% had a positive response to treatment, 42% were indeterminate or lacked documentation of response, and 7% had no response to treatment. Part 2 of the study demonstrated that 97% had a positive response to treatment, with 3% reporting no response to treatment. Acupuncture treatment did effectively decrease the symptomatology of the homeless clients seen in the Chicago Health Outreach Acupuncture Clinic. Further research should involve follow-up of these clients to assess the length of symptom relief to further determine long-range effectiveness and cost of treatment. PMID- 8195575 TI - Nursing diagnosis and natural therapies. A symbiotic relationship. AB - Work with nursing diagnosis has provided a classification system for what nursing does and has helped to focus nursing interventions to include more independent nursing care. Natural therapies (an umbrella term covering the many healing and health promotion modalities, traditional and modern, that do not use prescription pharmaceuticals or surgery) are among the more independent care modalities available to nursing. Accepted nursing interventions cover a growing number of practices, such as progressive relaxation, guided imagery, yoga, therapeutic touch, music therapy, active listening, aromatherapy, reflexology, advocacy, and centered presence. Most of these nursing interventions would seem to fit comfortably within the realm of natural therapies. As the illness-healing paradigms shift and converge, and the concept of holism rises more and more to the fore, the role of the nurse is shifting from caregiver to healer. Nursing diagnosis, as a classification system for nursing phenomena, can serve as a mechanism to enhance visibility of this healing role of the nurse. PMID- 8195576 TI - Caring incidents--a gift to the present. AB - The quality of health care in the United States has become a topic of national debate in the 1990s. Efforts are under way to eliminate inequities by providing educational strategies to monitor the administration of health care activities. In this article the author links the current proposals in the administration of health care to organizational strategies and to the humanistic approach to caregiving in nursing. Specific examples demonstrate how first-year nursing students are encouraged to integrate structured caring incidents into their clinical experiences. The article relies on the philosophical base provided by nurse theorist, Joyce Travelbee. She expressed concern that nursing care in institutions lacked compassion and needed a "humanistic revolution with a focus on caring" (Travelbee, 1991, p. 2). PMID- 8195577 TI - A holistic framework for nursing care. Rehabilitation of the myocardial infarction patient. AB - A holistic nursing framework to be used in the rehabilitation care of the myocardial infarction patient is discussed. Concepts of the framework include interplay of body-mind-spirit, negative life stress, coping modes, and their relationship to illness. Social support in the form of natural caring, together with one's own coping capacity, are usually enough to maintain health, integrity, control, and wholeness. But professional caring is needed when illness is perceived or symptoms develop. A holistic nursing intervention plan for the post MI patient is proposed. The aim of the article is to facilitate the use of the approach in research and in practice. PMID- 8195578 TI - Paroxetine in the elderly depressed patient: randomized comparison with fluoxetine of efficacy, cognitive and behavioural effects. AB - The efficacy of paroxetine and fluoxetine and their effects on cognitive and behavioural function were compared in a 6 week, double-blind, randomized study of 106 elderly depressed patients (aged 61 to 85 years). Antidepressant efficacy was assessed using the Hamilton depression rating scale (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) scale. The Sandoz Clinical Assessment Geriatric scale (SCAG), the Mini-Mental State Examination (MMSE), and HAMD cognitive factor scores were used to assess cognitive and behavioural function. Paroxetine demonstrated comparable efficacy to fluoxetine in the treatment of elderly depressed patients, but at the end of treatment, there was a significantly higher proportion of responders to paroxetine than to fluoxetine. Both treatments produced improvements in all measures of cognitive and behavioural function, but paroxetine was significantly superior to fluoxetine from Week 3, indicating a possible early effect. There was no difference between the two agents in either the tolerability or safety of treatment. PMID- 8195579 TI - Prediction of response to haloperidol in schizophrenia: neuroendocrine, neuromorphological and clinical variables. AB - Prediction of response to neuroleptics is a crucial topic since drug resistance phenomena can make the management of schizophrenia problematic and further deteriorate the outcome. Cerebral atrophy and enlarged ventricles have been suggested as the structural changes underlying negative symptoms and poor response to neuroleptic treatment. A higher percentage of non-suppressors to the dexamethasone suppression test (DST) among negative schizophrenics has been reported. Twenty-four schizophrenic in-patients, of both sexes, mean age 26.62 +/ 5.26 years, diagnosed according to DSM-III-R, with a mean duration of illness of 4.86 +/- 3.99 years, were treated with haloperidol 4-20 mg/day p.o. for 4 weeks. Clinical picture and extrapyramidal side effects were evaluated using BPRS and Simpson and Angus Scale at the beginning and end of the study. Ventricular brain ratio and basal and post-DST cortisol levels were evaluated at admission. The severity of the psychopathological picture, particularly positive symptoms at admission, were correlated to a higher amelioration at BPRS. Patients with ventricular enlargement and non-suppressors to DST showed higher variability of BPRS at baseline and more unpredictable clinical outcome than patients with normal ventricular brain ratio (VBR) and suppressors, even if a real difference in clinical outcome between patients characterized by normal or pathological parameters cannot be defined. PMID- 8195580 TI - Tolerability of combined treatment with lithium and fluoxetine: 14 cases treated under open conditions. AB - Fourteen cases of depression resistant to multiple treatments were treated by lithium augmentation of fluoxetine. Tolerability of the treatment was poor. Lithium and fluoxetine may be a possible treatment for resistant depression but there is caution regarding tolerability and toxicity with the relatively high doses of lithium used in this series. PMID- 8195581 TI - Verbal learning by major depressive disorder patients during treatment with fluoxetine or amitriptyline. AB - After 1 week of a single-blind placebo period, and prior to being randomly assigned to receive treatment with either fluoxetine or amitriptyline, patients meeting strict criteria for a diagnosis of major depressive disorder were given an auditory verbal learning test of working memory, and a blood sample was drawn. After 3 weeks of drug treatment with either amitriptyline or fluoxetine, the patients' symptoms were evaluated, the verbal learning test was repeated, and a second blood sample was taken. The clinical evaluation, the verbal learning test and the blood drawing were repeated a third time 3 weeks after the second assessment. The amount of anticholinergic activity in the blood samples was measured by a competitive radioligand binding assay and expressed in atropine equivalents. Analyses of variance indicated that there were no significant differences at the predrug Assessment 1 between patients subsequently assigned to the fluoxetine group compared with those assigned to the amitriptyline group. At Assessments 2 and 3, the fluoxetine and the amitriptyline groups showed equal clinical improvement but patients receiving amitriptyline did not perform as well on the verbal learning task. Serum anticholinergic activity at Assessments 2 and 3 was considerably higher in the amitriptyline group. This supports the hypothesis that blockade of muscarinic receptors impairs working memory formation. Equally effective antidepressant drugs with little or no anticholinergic action, such as fluoxetine, may be preferable in patients with pre-existing mild cognitive impairment or in patients where a slight reduction in cognitive performance is not acceptable. PMID- 8195582 TI - Alprazolam and amitriptyline in the treatment of moderate depression. AB - Forty-three out-patients with depression of a moderate degree were enrolled in a randomized, double-blind parallel group study comparing amitriptyline and alprazolam for 6 weeks of treatment. Patients were evaluated at the end of placebo washout and at Weeks 1, 2, 3 and 6 of drug therapy using the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory (BDI) and Clinical Global Impression (CGI). Drug dosage was determined in a fixed-flexible design resulting in mean final doses of alprazolam 3.2 mg/day and of amitriptyline 115 mg/day. Although both drug groups improved there were statistically significant differences in favour of amitriptyline at the end of the study on the HAM-D, BDI and HAM-A scales. Patients on amitriptyline reported more side effects overall than patients taking alprazolam with significantly more reports of dry mouth in the amitriptyline group. PMID- 8195583 TI - Selective serotonin reuptake inhibitors: meta-analysis of discontinuation rates. AB - A meta-analysis was carried out of 42 published randomized controlled studies comparing the selective serotonin reuptake inhibitors (SSRIs) with the tricyclic antidepressants (TCAs) that measured discontinuation rates for side effects and lack of efficacy by treatment group in order to compare the discontinuation rates for side effects and lack of efficacy. These discontinuation rates were pooled to produce the main outcome measure. Seven studies were placebo controlled and the discontinuation rates in these studies were also pooled in a separate analysis. Significantly fewer patients receiving SSRIs discontinued treatment because of side effects (14.9%) compared with those receiving TCAs (19%) (p < 0.01). There was also a significant difference in discontinuation rates due to side effects in the placebo- and TCA-controlled studies analysed separately, SSRIs (19%) compared with TCAs (27%) (p < 0.01). In both analyses a similar proportion of patients discontinued for lack of efficacy on SSRIs and TCAs. There is a significant and clinically important advantage for the SSRIs compared with the TCAs in the acceptability of treatment measured by the number of discontinuations due to side effects reported in published studies. The risk-benefit calculation favours the SSRIs since there were similar levels of efficacy but more discontinuations with the TCAs. The selection of an antidepressant for first-line treatment requires critical evaluation of the full risk-benefit equation. PMID- 8195584 TI - Adverse experiences during treatment with zimeldine on special licence in Sweden. AB - Adverse experiences during licensed treatment with the antidepressant serotonin (5-HT) reuptake inhibitor zimeldine in Sweden are presented. Data were obtained from a written inquiry of 694 patients and 67 reports to the Medical Products Agency. The spectrum of adverse symptoms was in agreement with those reported in previous studies on zimeldine. The most frequent adverse experiences were headache, nausea, myalgia, signs of liver function disturbance, arthralgia, neurological symptoms, fever and insomnia. No new case of the Guillain-Barre syndrome was found. The estimated frequency of the zimeldine-induced hypersensitivity syndrome (HSS), comprising fever, myalgia and/or arthralgia and signs of liver function disturbance, ranged from 1.4% to 13% in the inquiry and from 0.63% to 3.4% in the report part of the study. Adverse experiences usually had a considerably higher incidence during the first 6 weeks of zimeldine treatment than thereafter. This is in agreement with the clinical experience that most of the adverse reactions occur early during zimeldine treatment. However, a number of adverse experiences did occur with a later onset. This may justify a prolongation of the compulsory 4 weeks' testing of liver function that is required during licensed treatment. There were significantly fewer patients who developed fever among the patients who had experienced previous zimeldine treatment than among those who had not. Otherwise there was no statistically significant difference in frequency of adverse symptoms between these two groups. Consequently zimeldine treatment per se does not seem to predispose to development of an HSS or other types of adverse reactions during subsequent therapy. PMID- 8195585 TI - Daily fluctuation of plasma levels with conventional and controlled-release carbamazepine: correlation with adverse effects. AB - The pharmacokinetics, tolerability, and efficacy of carbamazepine (CBZ) and the pharmacokinetics of carbamazepine-10, 11-epoxide (CBZE) were studied after chronic administration of a conventional tablet formation or of the controlled release (CR) formulation of CBZ 400 mg (Tegretol 400) to 20 patients with epilepsy treated with carbamazepine and complaining of intermittent adverse effects. To compare the two formulations at the same doses and dose schedules, the study design had to be open, within-patient, with an initial 4 week period to individually adjust the dosage schedule with conventional CBZ followed by a 4 week period in which the CR formulation was substituted for conventional CBZ at the same daily dose and given by the same schedule. A further 4 week period was also studied to evaluate the same dosage of the CR formulation but given b.i.d. In this latter period six patients required an increase in dosage (200 mg/day). Before the beginning of the study and at the end of each period seizure frequency and tolerability were assessed. Tolerability was estimated with a specifically prepared scale that assesses the main items and with an overall rating scale. At the end of each treatment period, serum levels of CBZ and CBZE were determined at various times over a 10 h period. Peak plasma concentrations (Cmax) of CBZ and the fluctuation index (FI) were significantly lower for the CR CBZ, although minimal and mean plasma concentrations were the same in the three periods of the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195586 TI - Generation of allo-reactive cytotoxic T lymphocytes by particle bombardment mediated gene transfer. AB - Mature T lymphocytes comprise functionally distinct subsets with discrete roles in the regulation of the immune response. The cellular basis of the anti-tumor effect is now understood to involve the activation and expansion of tumor specific cytotoxic T lymphocytes (CTL). To immuno-potentiate the generation of CTL, we have employed the biolistic system for the genetic immunization of mice. Here, we report the efficient generation of anti-H-2Kb allo-reactive CTL by particle acceleration-mediated genetic immunization of mouse spleen cells with H 2Kb DNA. The insertion and expression of exogenous gene into host spleen cells following in situ genetic inoculation to effect the generation of a cellular immune response may permit novel alternative strategies for immunotherapy. PMID- 8195587 TI - Determination of haptoglobin expression in IL-6 treated HepG2 cells by ELISA and by RNA hybridization--evaluation of a quantitative method to measure IL-6. AB - Interleukin-6 (IL-6) is known to be an important modulator of acute phase (AP) protein expression in hepatocytes both in vivo and in vitro. In the present study the inducing activity of IL-6 on the expression of the AP protein haptoglobin (HP) by the human hepatoma cell line HepG2, has been evaluated. HP mRNA inducibility was analysed by Northern and slot-blot hybridization, while HP protein was detected by means of an ELISA procedure. A dose-response relationship from 0.3 to 4.8 ng/ml of a human recombinant IL-6 preparation derived from a Chinese hamster ovary (CHO) cell line was observed after 48 h of treatment. Comparable results were obtained by analysing both HP mRNA expression and HP protein secretion. Detectable induction of HP protein secretion was observed with as little as 25 pg/ml of IL-6. The effect of IL-6 was potentiated by dexamethasone, while an inhibition on HP mRNA inducibility could be prevented by lowering the foetal calf serum (FCS) concentration to 1%. Preliminary data indicate that neither IL-1 beta nor TNF-alpha were able to induce significantly HP mRNA expression and protein secretion. The activity ratio between two IL-6 preparations (from CHO and E. coli cells) obtained with a conventional IL-6 bioassay (i.e., T1165 cell growth assay) was comparable to that obtained in the induction of HP expression. The nominal specific activity of the CHO-derived IL-6 was two to three times higher with both responses. PMID- 8195588 TI - In vitro construction of graded thymus chimeras. AB - A simple in vitro approach is described for constructing chimeric thymi in which the degree of chimeric contribution can be tightly controlled. This is achieved by protease-assisted dissociation of fresh fetal thymic tissue, mixing the resulting cell suspensions at the desired ratios, and subsequent reaggregation. Analysis of these graded chimeras shows that stromal elements become evenly interspersed and form a microenvironment able to support the maturation of endogenous T cell precursors. Chimeras between normal and MHC-deficient thymi have been used to demonstrate the rescue of mutant, allotype-marked thymocytes by wild-type stromal cells. Other potential applications of the method include quantitative studies on positive and negative thymic selection, the functional role of defined stromal cell types in these processes, and the analysis of mutants (either natural or engineered) by complementation. PMID- 8195589 TI - New applications of carbonylmetalloimmunoassay (CMIA): a non-radioisotopic approach to cortisol assay. AB - A non-isotopic heterogeneous competitive immunoassay procedure, carbonylmetalloimmunoassay (CMIA) has been applied to the assay of cortisol. The organometallic tracers employed were two stereoisomers (Z and E) of certain cobalt carbonyl complexes of cortisol which have strong, characteristic v(CO) absorptions in the infrared, detectable by Fourier transform infrared (FT-IR) spectroscopy at the femtomole level. The separation of the free and bound organometallic-labelled fractions was achieved by solvent extraction with isopropyl ether. Complete characterization (i.e., dilution, competition and standard curves) of two different polyclonal anticortisol antibodies was possible using the CMIA method. Identical titre values were obtained for the two different stereoisomers used as tracers. In terms of the standard curves, however, the isomers behaved differently depending on which batch of antibody was used. When the best antibody/tracer pair (30 pmol of E isomer; anticortisol 1 antibody) was employed, we obtained a B/B(o)value at 50% of 42 +/- 2.12 pmol and a coefficient of variation of 5%. Finally, preliminary results of a CMIA analysis of plasma cortisol from a patient indicated that reliable and reproducible assays are possible for amounts as small as 50 microliters of serum. PMID- 8195590 TI - Chemical synthesis of bispecific monoclonal antibodies: potential advantages in immunoassay systems. AB - To date, the applications of bispecific antibodies in immunoassay and immunocytochemical procedures have been directed at uniting two different biomolecules through the binding of epitopes on each respective substance. In this study, bispecific antibodies were constructed in which both binding sites were directed to two different epitopes of the same target molecule. Two types of bispecific antibody were constructed; a bivalent bispecific monoclonal antibody and multivalent bispecific polymers. The binding characteristics of each were investigated for changes in specificity and binding strength relative to 1:1 mixtures of parent antibodies. A bivalent bispecific antibody (BBA) was synthesised by the method of Glennie et al. (1985) from monoclonal antibodies recognising the 'M' or 'B' units of creatine kinase (CKMB). The BBA had enhanced specificity for CKMB with diminished recognition of CKMM and CKBB. A less tedious method of producing bispecific antibody involving heterobifunctional cross linkage was used to produce multivalent bispecific antibodies (MBAs). Certain MBAs constructed to bind 'M' and 'B' units of CKMB demonstrated enhanced specificity and affinity for CKMB. MBAs were also produced to opposite ends of the 39 amino acid peptide adrenocorticotrophic hormone (ACTH). One of these demonstrated an enhanced affinity of 41-fold. We conclude that while conventional synthesis of bispecific bivalent antibodies is not a practical proposition for immunoassay development, antibodies with similar advantages can be produced with a simple method using the heterobifunctional cross-linker. The production of certain bispecific antibody combinations appears to enhance the formation of antibody-antigen matrices conferring higher binding affinities than can be achieved with an antibody mixture alone. PMID- 8195591 TI - Preparation of F(ab')2 mu fragments from rat IgM monoclonal antibodies and their application to the enzyme immunoassay of mouse interleukin-6. AB - F(ab')2 fragments, herein designated as F(ab')2 mu, were prepared from rat IgM monoclonal antibodies (mAbs). The IgM was digested at a pepsin-to-IgM ratio of 1:200 (w/w) in 100 mM citrate buffer (pH 4.5) at 37 degrees C for 2 h. During digestion, the light (L) chain (27 kDa) of IgM remained undegraded, whereas the heavy (H) chain disappeared and two new bands of 44 and 48 kDa appeared. The digests were fractionated by means of hydrophobic interaction HPLC with TSKgel Phenyl-5PW. The fraction containing F(ab')2 mu was homogeneous and the recovery of antigen-binding activity was 41-52%. The molecular mass of F(ab')2 mu was estimated to be 147-153 kDa, and we concluded that the fragment was composed of two truncated H chains and two intact L chains. F(ab')2 mu was used in an enzyme immunoassay of mouse interleukin-6 and the interaction of IgM with non-specific proteins was greatly reduced, when it was converted to F(ab')2 mu fragments. PMID- 8195592 TI - The development of an assay for human neutrophil lipocalin (HNL)--to be used as a specific marker of neutrophil activity in vivo and vitro. AB - Human neutrophil lipocalin (HNL) is a newly discovered protein from human neutrophil secretory granules. A double-antibody radioimmunoassay (RIA) was developed for the measurement of HNL in various body fluids and its high specificity was confirmed by the absence of cross-reaction with other granulocyte granule proteins. The RIA measures HNL within the range of 4-256 micrograms/l. The intra- and interassay coefficients of variation were less than 6% and 10%, respectively. When HNL was added to serum samples full recovery was obtained. Sera and plasma from 100 apparently healthy individuals revealed a mean level of 78.40 micrograms/l (range 37.95-190.87 micrograms/l) in serum and a mean level of 50.65 micrograms/l (range 30.51-105.8 micrograms/l) in EDTA-plasma. The distribution of HNL after gel filtration indicated that HNL exists mainly in two major forms, dimer and monomer. This, in addition to the excellent recovery, suggests that these major forms of HNL do not bind to compounds in serum or plasma that would interfere with the assay. The high specificity, sensitivity, reproducibility and accuracy of the present assay should facilitate the measurement of HNL in blood and other body fluids. PMID- 8195593 TI - Enhanced cloning efficiencies of murine hybridomas using human plasma supplemented medium. AB - Normal human plasma and plasma from patients with chronic lymphocytic leukemia (CLL) were used as growth supplements for the cloning of murine hybridomas. Basal medium, consisting of DMEM with 5% foetal calf serum (FCS) was conditioned with supernatant from a known human IL-6-secreting cell line, BRI-6 (BRI-6-CM), normal human plasma (NHP-DMEM), and plasma from patients with CLL (CLL-DMEM). When compared to conventional feeder layers of macrophages, thymocytes, splenocytes and to feeder CLL cells and BRI-6-CM the numbers of clones formed by growing hybridomas in CLL-DMEM was greatly enhanced with a corresponding increase in the number of antibody-producing clones, as determined by ELISA. NHP-DMEM also enhanced the cloning efficiency. All CM and plasma supplemented medium were examined for the presence of interleukin-6 (IL-6). Of eight CLL plasma samples examined only two had elevated IL-6 levels. PMID- 8195594 TI - A highly sensitive non-radioactive cytotoxicity assay for human target cells. PMID- 8195595 TI - A bioassay for the detection of tumor necrosis factor from eight different species: evaluation of neutralization rates of a monoclonal antibody against human TNF-alpha. AB - We have evaluated a recently developed bioassay based on porcine kidney (PK(15)) cells for the detection of tumor necrosis factor-alpha (TNF-alpha) from eight different species. This test could also be used to measure human TNF-beta with similar sensitivity when compared to the widely used L929 bioassay. PMID- 8195596 TI - Health care reform: implications for professions related to infectious diseases. PMID- 8195597 TI - The influence of attitudes on the response to AIDS in the United States. PMID- 8195598 TI - Lessons from diarrheal diseases: demography to molecular pharmacology. AB - From diarrheal diseases come profound lessons about health and population growth, microbial pathogenesis, and the molecular pharmacology of signal transduction. Epidemics such as cholera, hemorrhagic colitis, salmonellosis, and cryptosporidiosis remind us of how interdependent we are, sharing enteric microbial flora on a global scale. Diarrhea morbidity and mortality teach us that disease and poverty do not control but are associated with population overgrowth. Great advances are being made in understanding new bacterial, viral, and parasitic causes and treatment of diarrhea, especially persistent diarrhea. In addition, microbial toxins provide unique pharmacologic tools to probe cell signaling pathways. The mechanism of action of cholera toxin, once thought so clear, now appears to involve additional pathways such as platelet-activating factor and prostaglandin synthesis. Escherichia coli ST has opened a whole family of activators of guanylate cyclase, including new mammalian products that regulate sodium transport. Clostridium difficile toxin A provides a novel tool to dissect mediators involved in inflammatory diarrhea. These lessons have both basic implications for science and practical applications for medicine and society. PMID- 8195599 TI - Assessment of hepatitis C virus RNA levels by quantitative competitive RNA polymerase chain reaction: high-titer viremia correlates with advanced stage of disease. AB - A quantitative competitive RNA polymerase chain reaction (QC-PCR) assay was developed for measuring absolute levels of hepatitis C virus (HCV) RNA in the sera of 121 viremic persons, including 64 asymptomatic blood donors, 39 symptomatic patients referred for treatment of chronic hepatitis C, and 18 patients with end-stage liver disease referred for liver transplantation. Mean HCV RNA levels (log molecules per milliliter) were lowest among blood donors with normal alanine aminotransferase (ALT) values (5.8 +/- 1.5), higher among blood donors with elevated ALT (6.9 +/- 0.8) and clinic patients with chronic active hepatitis (6.9 +/- 0.7), and highest among patients with cirrhosis (7.1 +/- 0.8) or end-stage liver disease (7.6 +/- 1.0). High-titer viremia ( > or = 7.5 logs/mL) was more frequent among patients with end-stage liver disease (14/18; 78%) than either blood donors (10/64; P < .001) or patients with chronic active hepatitis (7/26; P < .001). Thus, 121 (94.5%) of 128 anti-HCV-positive persons were viremic. QC-PCR may be valuable for monitoring HCV infection status and selecting individuals for therapy. PMID- 8195600 TI - Associations between HLA frequencies and pathogenic features of human immunodeficiency virus type 1 infection in seroconverters from the Amsterdam cohort of homosexual men. AB - HLA-disease associations may be important for understanding the pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection. Therefore, 106 homosexual men from the Amsterdam Cohort Study on AIDS with a known date of HIV-1 seroconversion were serologically typed for HLA. Several significant associations between HLA type and pathogenic features of HIV-1 infection were observed: Subjects with fever and skin rash during primary HIV-1 infection showed an increased frequency of HLA-B62 (relative risk [RR], 5.8; P = .005). The frequency of HLA-B35 was increased in subjects with a rapid decline in CD4+ T lymphocytes (RR, 3.2; P = .021). Kaplan-Meier survival analysis revealed a significant association between HLA-B35 and a decrease in CD4+ cells to < 200/microL (P = .01). The strongest association was found between HLA-DR1 and AIDS-related Kaposi's sarcoma (RR, 22.5; P < .001), also confirmed in survival analysis (P = .001). In AIDS patients with only opportunistic infections, increased frequencies of HLA-DR3 (P = .011) and -DQ2 (P = .007) were observed. Finally, the occurrence of syncytium-inducing HIV-1 variants was significantly associated with HLA-DQ2 (P = .01). PMID- 8195601 TI - Analysis of potential risk factors associated with the development of pancreatitis in phase I patients with AIDS or AIDS-related complex receiving didanosine. AB - Phase I dose-escalating trials of didanosine revealed dose-limiting toxicities, including pancreatitis, and established a total daily dose of 12.5 mg/kg/day as the maximum tolerated dose. Clinical and pharmacokinetic data of 61 patients from two trials were analyzed to further evaluate the risk of pancreatitis: 1 (6.3%) of 16 patients who received < 500 mg/day didanosine, 2 (13.3%) of 15 who received 500-750 mg/day, and 15 (50%) of 30 who received > 750 mg/day developed pancreatitis (P < .001). A relationship between risk of pancreatitis and steady state plasma concentrations of didanosine and age was also observed, suggesting that knowledge of didanosine pharmacokinetics provided additional information regarding risk of toxicity. Further confirmation of these findings will be necessary to determine if the risk factors for pancreatitis remain the same at lower doses currently used. PMID- 8195602 TI - Virus and bacteria enhance histamine production in middle ear fluids of children with acute otitis media. AB - Histamine levels were measured in 677 middle ear fluid (MEF) samples from 248 children (aged 2 months to 7 years) with acute otitis media (AOM); of these, 116 (47%) had documented viral infection. Histamine content was higher in bacteria positive than in bacteria-negative MEF samples (P = .007) and higher in samples from patients with viral infection than in those from patients with no viral infection (P = .002). Bacteria and viruses together had an additive effect on histamine content in MEF. Histamine concentration in the initial MEF sample tended to be higher in patients with persistent otitis than in those with good response to treatment (P = .14). Results suggest that viruses, bacteria, or both induce histamine production, which leads to increased inflammation in the middle ear. Antihistaminic drugs may be beneficial. Large, prospective, controlled trials of the effects of antihistamine as an adjunct therapy in bacterial and viral AOM are required before recommendations can be made. PMID- 8195603 TI - Serologic and genetic identification of Peromyscus maniculatus as the primary rodent reservoir for a new hantavirus in the southwestern United States. AB - An outbreak of hantavirus pulmonary syndrome (HPS) in the southwestern United States was etiologically linked to a newly recognized hantavirus. Knowledge that hantaviruses are maintained in rodent reservoirs stimulated a field and laboratory investigation of 1696 small mammals of 31 species. The most commonly captured rodent, the deer mouse (Peromyscus maniculatus), had the highest antibody prevalence (30%) to four hantavirus antigens. Antibody also was detected in 10 other species of rodent and in 1 species of rabbit. Reverse transcriptase polymerase chain reaction (RT-PCR) products of hantavirus from rodent tissues were indistinguishable from those from human HPS patients. More than 96% of the seropositive P. maniculatus were positive by RT-PCR, suggesting chronic infection. Antibody prevalences were similar among P. maniculatus trapped from Arizona (33%), New Mexico (29%), and Colorado (29%). The numeric dominance of P. maniculatus, the high prevalence of antibody, and the RT-PCR findings implicate this species as the primary rodent reservoir for a new hantavirus in the southwestern United States. PMID- 8195604 TI - Human herpesvirus 6 infection of the female genital tract. AB - Four of the seven human herpesviruses are recognized to replicate in the female genital tract and may be transmissible to sexual partners and newborn infants. Several of these viruses have also been implicated in the etiology of various human cancers, including tumors of epithelial cell origin. Human herpesvirus 6 (HHV-6) is a newly identified herpesvirus that causes exanthem subitum. The pathogenicity of HHV-6 within the genital tract is largely unexplored. Acellular vaginal secretions from 29 women attending a sexually transmitted diseases clinic were examined for the presence of HHV-6 DNA sequences by polymerase chain reaction. Three samples (10%) were consistently positive for HHV-6 DNA. Since HHV 6 DNA is shed in the genital tract of some women, it is possible that infectious virus is transmissible through sexual contact and to newborn infants by perinatal spread. PMID- 8195605 TI - A primate model for chancroid. AB - Adult pigtailed macaques (Macaca nemestrina) were evaluated for their usefulness as a primate model for chancroid. To initiate infection, 10(7)-10(8) cfu of Haemophilus ducreyi were inoculated into the foreskins of 5 adult males and into the vaginal labia of 4 adult females. Lesions developed in the male macaques that were similar in appearance, histopathologic changes, and progression to those of human disease, including the development of ulcers 6-12 days after infection. In addition, H. ducreyi could be recovered from the lesions up to 20 days after inoculation, humoral antibodies were induced beginning 1 week after inoculation, and inguinal lymphadenopathy was noted in 4 of the 5 males. None of the 4 female macaques inoculated with the same preparation of live H. ducreyi developed comparable lesions. Thus, experimental chancroid in adult male macaques closely resembles human disease and should be useful for future studies of the pathogenesis of chancroid. PMID- 8195606 TI - Oligosaccharide sequences attached to an inert support (SYNSORB) as potential therapy for antibiotic-associated diarrhea and pseudomembranous colitis. AB - Toxin A produced by Clostridium difficile, the causative agent of pseudomembranous colitis and antibiotic-associated diarrhea, was shown to bind to synthetic oligosaccharide sequences attached to an inert support (SYNSORB). The oligosaccharide sequences that bind to toxin A were related to sequences previously identified as potential receptors for the toxin. Various SYNSORBs containing a variety of oligosaccharides were examined for their potential to neutralize toxin A activity from toxin-containing solutions as well as clinical stool samples from patients with either pseudomembranous colitis or antibiotic associated diarrhea. The results from neutralization experiments suggest SYNSORB can effectively neutralize toxin A activity from stool samples and thus could serve as a potential therapy for C. difficile-associated diarrhea. PMID- 8195607 TI - Pertussis in Massachusetts, 1981-1991: incidence, serologic diagnosis, and vaccine effectiveness. AB - Massachusetts provides diphtheria-tetanus toxoid-pertussis (DTP) vaccine, and since 1980 has monitored pertussis with a statewide diagnostic service. The incidence of bacteriologically confirmed pertussis was 104.5 per 100,000 person years in 1-month-old infants and declined progressively thereafter. Infants < 6 months old experienced disproportionate morbidity: 44% of bacteriologically confirmed pertussis, 64% of hospitalizations, and 71% of hospital days. Most children with pertussis had received < 3 DTP doses during childhood, whereas 87% of adolescents with pertussis had received > or = 4 doses. Serodiagnosis by single serum anti-pertussis toxin antibody ELISA increased the incidence of confirmed pertussis in persons 11-19 years old from 3.0 to 12.9 per 100,000 and in persons > or = 20 years old from 0.16 to 0.56 per 100,000. Bacteriologic methods underestimate pertussis incidence, but a single serum anti-pertussis toxin antibody ELISA is a practical method for population-based diagnosis in adolescents and adults. PMID- 8195608 TI - Patterns of proinflammatory cytokines and inhibitors during typhoid fever. AB - Cytokines and inhibitors in plasma were measured in 44 patients with typhoid fever. Ex vivo production of the cytokines was analyzed in a whole blood culture system with and without lipopolysaccharide (LPS). Acute phase circulating concentrations of cytokines (+/- SD) were as follows: interleukin (IL)-1 beta, < 140 pg/mL; tumor necrosis factor-alpha (TNF alpha), 130 +/- 50 pg/mL; IL-6, 96 +/ 131 pg/mL; and IL-8, 278 +/- 293 pg/mL. Circulating inhibitors were elevated in the acute phase: IL-1 receptor antagonist (IL-1RA) was 2304 +/- 1427 pg/mL and soluble TNF receptors 55 and 75 were 4973 +/- 2644 pg/mL and 22,865 +/- 15,143 pg/mL, respectively. LPS-stimulated production of cytokines was lower during the acute phase than during convalescence (mean values: IL-1 beta, 2547 vs. 6576 pg/mL; TNF alpha, 2609 vs. 6338 pg/mL; IL-6, 2416 vs. 7713 pg/mL). LPS-stimulated production of IL-1RA was higher in the acute than during the convalescent phase (5608 vs. 3977 pg/mL). Inhibited production of cytokines during the acute phase may be due to a switch from a proinflammatory to an antiinflammatory mode. PMID- 8195609 TI - Epidemiology of Moraxella catarrhalis in children during the first 2 years of life: relationship to otitis media. AB - Nasopharyngeal colonization with Moraxella catarrhalis was evaluated in a large cohort of infants followed prospectively from birth to 2 years of age; 120 children were examined at 13 routine visits. Of these, 66% became colonized with M. catarrhalis by 1 year and 77.5% by 2 years. Nasopharyngeal colonization with M. catarrhalis increased from 27.0% during healthy visits to 62.7% during visits due to otitis media (P < .001). Otitis-prone children were colonized at 44.4% of all visits compared with 16.7% for children who did not have otitis media (P < .001). DNA from 112 strains of M. catarrhalis from 34 children were evaluated; 106 were successfully digested with restriction enzymes and demonstrated a great degree of heterogeneity. Children tended to acquire and eliminate a number of different strains. Intrafamilial spread of the same strain of M. catarrhalis was frequent. These data suggest that nasopharyngeal colonization with M. catarrhalis is common throughout infancy. A high rate of colonization is associated with an increased risk of otitis media. PMID- 8195610 TI - Activity of isepamicin and selection of permeability mutants to beta-lactams during aminoglycoside therapy of experimental endocarditis due to Klebsiella pneumoniae CF104 producing an aminoglycoside acetyltransferase 6' modifying enzyme and a TEM-3 beta-lactamase. AB - The pharmacokinetics and efficacy of isepamicin were compared with those of amikacin and gentamicin in a rabbit model of endocarditis due to Klebsiella pneumoniae CF104 producing beta-lactamase TEM-3 and aminoglycoside acetyltransferase AAC(6')-IV. Only isepamicin and gentamicin, alone or combined with ceftriaxone, were effective as determined by titration of viable bacteria in vegetations. Variants highly resistant to ceftriaxone without change in MICs of aminoglycosides were isolated at the end of each therapeutic regimen except with the most effective one (ceftriaxone plus gentamicin). Examination of the bacterial outer membrane proteins as well as the 50% inhibition of the beta lactamase activity in intact and sonified cells suggested a permeability defect as being responsible for the increased MICs of ceftriaxone. The activity of isepamicin was superior to that of amikacin against the TEM-3-AAC(6')-IV producing strain. The combination of gentamicin plus ceftriaxone was the most effective regimen in terms of efficacy and prevention of emergence of resistant strains. Suboptimal aminoglycoside monotherapy might be responsible for selection of permeability mutants to beta-lactams. PMID- 8195612 TI - The role of the major histocompatibility complex in human immunodeficiency virus infection--ever more complex? PMID- 8195611 TI - Cure of murine candidiasis by recombinant soluble interleukin-4 receptor. AB - Neutralization of interleukin (IL)-4 by specific antibody exerts therapeutic activity in a murine model of systemic candidiasis characterized by strong T helper type 2 (Th2) responses. To investigate whether recombinant soluble IL-4 receptor (sIL-4R) could be used to block IL-4 action in vivo, mice treated with pharmacologic doses of sIL-4R at the time of infection were examined for progression of disease, development of footpad responses, serum IgE levels, and cytokine production in vitro by CD4+ lymphocytes. Following sIL-4R treatment, persistent ablation of circulating IL-4 detected by ELISA was associated with a cure rate of > 90% in otherwise lethally infected mice, onset of durable protection, and a shift from a predominant Th2 to a Th1 pattern of reactivity. In addition, when administered to genetically susceptible adult mice with gastrointestinal yeast colonization, the sIL-4R stimulated Th1-associated anticandidal resistance. PMID- 8195613 TI - Polymerase chain reaction to detect cytomegalovirus DNA in the cerebrospinal fluid of neonates with congenital infection. AB - To determine if cytomegalovirus (CMV) DNA could be detected in the cerebrospinal fluid (CSF) of infants with congenital infection with CMV, polymerase chain reaction (PCR) was done on CSF samples from 13 infants (10 with confirmed, 1 with possible, and 2 with asymptomatic congenital CMV infection) and on CSF samples from 100 control patients with alternative diagnoses. By use of two sets of primers that targeted different areas of the CMV genome, CMV DNA was amplified in the CSF of 6 of 10 symptomatic infants, 0 of 3 infants with asymptomatic CMV infection or possible congenital CMV disease, and 2 control patients (one primer set only). A positive CSF PCR result at birth correlated with a poor neurodevelopmental outcome (P = .048; two-tailed Fisher's exact test). PMID- 8195614 TI - Recurrence and resistance patterns of herpes simplex virus following cessation of > or = 6 years of chronic suppression with acyclovir. Acyclovir Study Group. AB - Questions have arisen regarding the clinical outcome and the possible selection of resistant virus when patients with genital herpes discontinue prolonged chronic acyclovir; 239 immunocompetent patients with a history of frequently recurring genital herpes who stopped successful suppressive therapy after 6 years were studied. Of the patients, 85.8% had at least one recurrence and 75% had at least two recurrences in the subsequent year (median time to first and second recurrence, 68 and 180 days, respectively). Herpes simplex virus isolates recovered from these patients had a median acyclovir sensitivity of 0.79 micrograms/mL and 4 (3.5%) were resistant (> or = 3 micrograms/mL). These values are comparable to those of pretherapy isolates and to reported values of isolates from acyclovir-naive patients. Also, paired pre- and posttherapy isolates from 13 patients showed no trend toward development of resistance. Thus, even after 6 years of acyclovir suppression, most patients continue to have recurrences, but the selection of resistant virus has not been observed. PMID- 8195615 TI - Alternating nevirapine and zidovudine treatment of human immunodeficiency virus type 1-infected persons does not prolong nevirapine activity. AB - The potential use of an alternating treatment strategy with nevirapine and zidovudine in prolonging the antiretroviral effects of nevirapine was evaluated. Ten human immunodeficiency virus type 1 (HIV-1)-infected p24 antigen-positive persons who had not received prior antiretroviral therapy were treated for 9-13 weeks with an alternating regimen of 1 week of nevirapine (200 mg/day) and 3 weeks of zidovudine (600 mg/day). Serum p24 antigen levels declined during the first week of nevirapine treatment (median, 59%); however, subsequent courses of nevirapine were characterized by rising p24 antigen levels, while antigen levels remained stable or declined during zidovudine treatment. Serum beta 2 microglobulin levels and CD4+ cell counts exhibited similar responses. HIV-1 isolates obtained from 2 patients revealed 40- and 1000-fold reductions in nevirapine sensitivity after 8 weeks. These findings demonstrate that alternating treatment with zidovudine and nevirapine does not prolong the effectiveness of nevirapine and does not prevent the development of nevirapine resistance. PMID- 8195616 TI - False-positive rapid plasma reagin tests in human immunodeficiency virus infection and relationship to anti-cardiolipin antibody and serum immunoglobulin levels. AB - The incidence of biologic false-positive rapid plasma reagin (RPR) tests may be increased in human immunodeficiency virus (HIV) infection; however, injecting drug use has not been excluded as the cause. Review of 3371 periodic syphilis serology results from 1077 HIV-seropositive patients in the United States Air Force HIV Natural History Study between January 1986 and June 1992 revealed a cumulative biologic false-positive RPR rate of 1%. Most (6/9) were transient low titer results associated with a recent acute infectious process. False-positive RPR tests did not appear to correlate with anticardiolipin antibody levels or serum IgG or IgA levels, which are increased in HIV infection. Although not statistically significant, there was a trend toward higher IgM levels in patients with biologic false-positive tests. Thus, the incidence of false-positive RPR in an HIV-infected population with a low risk of injecting drug use is similar to that in the general population, and the mechanism may correlate with elevated serum IgM levels. PMID- 8195617 TI - Glycoforms of alpha 1-acid glycoprotein in sera of human immunodeficiency virus infected persons. AB - In acute infections thus far studied, there is a relative increase in plasma protein glycoforms rich in biantennary complex type N-glycans (type I), while in some diseases with chronic inflammatory changes, there is increase in glycoforms with more branched N-glycans (type II). In sera of 109 human immunodeficiency virus (HIV)-infected persons, 38 rheumatoid arthritis patients, and 44 healthy subjects, the composition of alpha 1-acid glycoprotein (AGP) glycoforms was studied using crossed immunoaffinity electrophoresis with concanavalin A as a ligand. In patients in CDC classifications I, II, and III, distribution of AGP glycoforms was analogous to that in normal subjects. Type I alterations were observed in patients in group IV who had no signs of arthritis. Type II changes, analogous to those found in rheumatoid arthritis, were seen in group IV patients who developed arthritis. Most significant type I changes were associated with Pneumocystis carinii pneumonia (specificity, 100%; sensitivity, 96%). PMID- 8195618 TI - Detection of Norwalk virus or Norwalk-like virus infections in Finnish infants and young children. AB - Norwalk virus (NV) and Norwalk-like viruses are important causes of epidemic nonbacterial gastroenteritis in older children and adults. Serologic responses to NV of 154 Finnish infants and young children participating in a rotavirus vaccine study were examined by ELISA with a recently available baculovirus-expressed recombinant NV capsid protein. In 4 serially collected sera (at the median ages of 3, 4, 14, and 23 months), 49% of children had at least one NV infection over the approximately 2-year study period. Children with low NV-specific IgG titers (< 1:50) at the median age of 4 or 14 months were significantly more likely to acquire an NV infection by the median age of 14 or 23 months, respectively, than children who had higher NV IgG titers (> 1:50) (P < .05). Thus, NV or Norwalk like virus infections are more common in infants and young children than previously believed, and antibody to NV may be protective against such infections. PMID- 8195620 TI - Breakthrough infections and identification of a viral variant in Gambian children immunized with hepatitis B vaccine. AB - Hepatitis B (HB) breakthrough infections, identified by the presence of HB core (c) antibody, were found in 32 of 358 Gambian children vaccinated with plasma derived HB vaccine. Over 2 years, 15 of these children lost their HBc antibodies. These children had significantly higher HB surface antibody levels before infection than those who retained HBc antibodies. One child, who responded well to the vaccine, had HB viral DNA detected in the presence of HBs antibodies. The S gene sequence of this DNA showed nucleotide changes that resulted in an amino acid substitution at residue 141 (lysine to glutamic acid) of the surface antigen. This finding suggests the child was infected with a variant virus that was not neutralized by antibodies resulting from HB vaccination. PMID- 8195619 TI - Comparison of antibody concentrations and protective activity of respiratory syncytial virus immune globulin and conventional immune globulin. AB - Relative to conventional immune globulins (IG, 13 lots), IGs prepared from donors with high activity by microneutralization assay to respiratory syncytial virus (RSVIG, 8 lots) had significantly higher neutralizing antibodies to 6 RSV strains (mean enrichment, 5.2-fold; range, 2.6- to 10.0-fold). In contrast, IgG antibody concentrations to whole RSV, fusion protein, or glycoproteins of A and B strains were similar in RSVIG and IG. Treatment of cotton rats with RSVIG at 0.5 g/kg 24 h before RSV challenge reduced RSV by 99% in the lungs (P < .001). RSVIG at 5.0 g/kg reduced RSV by 99% in the nose. IG at 5.0 g/kg had efficacy similar to that of RSVIG at 0.5 g/kg. Serum plaque-reduction neutralization titers of 1/390 resulted in 99% reduction of lung RSV and titers of 1/3500 resulted in 99% reduction in nose RSV. Relative to IG, RSVIG is enriched selectively in RSV neutralizing antibodies and has approximately 10 times greater protective activity in cotton rats. PMID- 8195621 TI - Measles virus-specific functional antibody responses and viremia during acute measles. AB - Antibody titers measured in functional and immunofluorescent assays were compared with proportions of peripheral blood mononuclear cells infected with measles virus in 8 adults with measles. In addition, a syncytium inhibition assay (SIA) for measuring neutralizing antibody using low-passage virus was compared with a standard plaque neutralization test (PNT). Antibody-dependent cellular cytotoxicity (ADCC) antibody rose later but attained higher titer than neutralizing, antibody-dependent complement-mediated lysis, IgM, or IgG antibodies. When titer changes between specimens from each patient obtained on different days were compared, only ADCC (r = .81, P = .026) and IgM (r = .81, P = .027) antibodies correlated with reductions in viremia. SIA and PNT correlated well (r = .93, P < .001). ADCC may be an important defense against measles. The delay in ADCC antibody relative to other antibodies is unique among viruses studied. The SIA is a useful alternative to the PNT for measuring measles neutralizing antibody. PMID- 8195622 TI - Epidemic cholera in the Amazon: the role of produce in disease risk and prevention. AB - Epidemic cholera struck Peru in January 1991 and spread within a month to the Amazon headwaters. A case-control study was done in the Amazonian city of Iquitos, Peru. Cholera-like illness was associated with eating unwashed fruits and vegetables (odds ratio [OR] = 8.0; 95% confidence limits [CL] = 2.2, 28.9) and drinking untreated water (OR = 2.9; 95% CL = 1.3, 6.4). Consumption of a drink made from toronja, a citrus fruit, was protective against illness (OR = 0.4; 95% CL = 0.2, 0.7). Illness was inversely associated with the quantity of toronja drink consumed (P < .01). Produce has not previously been convincingly documented as a risk factor for cholera; this study underscores the importance of washing produce before eating it. Acidic juices, such as toronja drink (pH 4.1), inhibit vibrio growth and may make contaminated water safer. Wild citrus fruits such as toronja are abundant, cheap, and popular in the Amazon region. Promoting the consumption of toronja drink may be a useful cholera prevention strategy in this region. PMID- 8195623 TI - Use of arbitrarily primed polymerase chain reaction analysis to type disease and carrier strains of Neisseria meningitidis isolated during a university outbreak. AB - Disease and carrier isolates of Neisseria meningitidis from two regions of the United States were typed by the arbitrarily primed polymerase chain reaction (PCR), or random amplified polymorphic DNA (RAPD), method. This technique generates strain-specific arrays of amplified DNA fragments using low-stringency PCR with single, arbitrarily chosen primers. Each of 3 disease isolates and 7 of 11 carrier isolates from an outbreak at the University of Connecticut were indistinguishable using each of 4 primers. In contrast, 22 other isolates (the remaining 4 carrier isolates plus 18 disease and carrier isolates from Connecticut, Illinois, and Missouri) were divided into 18 sets using the same 4 primers. This outcome supports the view that disease isolates from an outbreak may reflect sporadic invasive progression by a strain that also frequently causes asymptomatic colonization. Our results show that RAPD tests provide a sensitive and efficient means of distinguishing genetically different meningococcal strains and that they should facilitate clinical, epidemiologic, and population genetic studies of this important pathogen. PMID- 8195624 TI - Screening and treatment of asymptomatic bacteriuria in pregnancy prevent pyelonephritis. AB - Although asymptomatic bacteriuria during pregnancy is associated with an increased risk of developing pyelonephritis, the effectiveness of screening programs to reduce this risk is controversial. A sharp reduction in the annual incidence of pyelonephritis (1.8% to 0.6%, P < .001) occurred after the introduction of a program to screen and treat asymptomatic bacteriuria among pregnant women followed at a large teaching hospital. The data provide retrospective and prospective evidence that screening and treatment programs for asymptomatic bacteriuria during pregnancy reduce the risk of pyelonephritis in a population with a moderate to high prevalence of bacteriuria. PMID- 8195625 TI - Molecular epidemiology of coagulase-negative Staphylococcus blood isolates from neonates with persistent bacteremia and children with central venous catheter infections. AB - Multilocus enzyme electrophoresis was used to genetically characterize sequential isolates of coagulase-negative staphylococci (CONS) from 3 neonates with persistent bacteremia and organisms cultured from several sites in 23 children with presumed catheter-related sepsis (CRS). For 2 of 3 neonates and 21 (91%) of 23 of the patients with presumed CRS, the same CONS clone was isolated from multiple consecutive blood cultures (mean, 7.3 isolates; range, 3-19). For the 23 children with presumed CRS, 7 (30%) had catheter hub (CH) and 7 (30%) had catheter exist site (CES) cultures positive for CONS; cultures from 3 of these patients (from both CH and CES) grew CONS. Genetic analysis of isolates recovered from the CH and peripheral and central venous catheter blood cultures of all 7 patients revealed clonal identity of the strain grown from all sites. In contrast, only 4 (57%) of 7 of the CONS isolates from the CES were the same clone as that isolated from the blood. These data suggest that repetitive isolation of CONS during the course of CRS is due to ongoing bacteremia, not culture contamination with distinct CONS isolates. The results also are consistent with the hypothesis that the CH is a more likely site of initial colonization by CONS than the exist site in patients with CRS. PMID- 8195626 TI - Role of amoxicillin serum levels for successful prophylaxis of experimental endocarditis due to tolerant streptococci. AB - The importance of amoxicillin serum profiles for successful prophylaxis of experimental endocarditis in rats was assessed. Animals with catheter-induced vegetations were challenged intravenously with large inocula of Streptococcus sanguis and received one of the following amoxicillin dosages: single or multiple bolus injection of 40 mg/kg; 40 mg/kg administered as a continuous infusion over 12 h; or either 9 or 18 mg/kg administered over 12 or 24 h, respectively. The regimen producing a single transient high peak serum level failed to prevent experimental endocarditis; in contrast, a second injection 6 h after the first resulted in successful prophylaxis. Likewise, the three regimens of continuous, relatively low-dose regimens prevented infections. Thus, the most important parameter for successful prophylaxis was the duration of inhibitory concentration of the drug in the serum. The total dose of antibiotic, the peak serum levels, or the area-under-the-curve values were not predictive of successful prophylaxis. PMID- 8195627 TI - Acyclovir prophylaxis for cytomegalovirus in liver transplant recipients. PMID- 8195628 TI - Capacity of human immunodeficiency virus type 1 to infect chimpanzee monocytes in vitro. PMID- 8195629 TI - Lymphocyte subset alterations associated with increased spontaneous lymphocyte proliferation in human T lymphotropic virus (HTLV) infection: distinctive patterns for HTLV-I versus HTLV-II infection. PMID- 8195630 TI - Detecting Borrelia burgdorferi in blood from patients with Lyme disease. PMID- 8195631 TI - Lower serum hepatitis C virus RNA titers in patients with concurrent chronic hepatitis B virus infection. PMID- 8195632 TI - Non-O1 Vibrio cholerae O139 Bengal is genetically related to V. cholerae O1 El Tor Ogawa isolated in Mexico. PMID- 8195633 TI - Dihydropteroate synthetase antibodies. PMID- 8195634 TI - Association between HLA-DR13 and susceptibility to alveolar echinococcosis. PMID- 8195635 TI - Nitric oxide in cerebral malaria. PMID- 8195636 TI - Patients with Plasmodium falciparum malaria and Plasmodium vivax malaria show increased nitrite and nitrate plasma levels. PMID- 8195637 TI - Interleukin-1 alpha administration increases oral granulocytes and epithelial cells. PMID- 8195638 TI - Pancreatic enzymes in chronic pancreatitis. PMID- 8195639 TI - Reliability of pancreatic cancer staging classifications. AB - The prognostic value of UICC and JPS classifications was evaluated in a group of 74 patients undergoing resection for pancreatic carcinoma in the 1982-1992 period. The predictivity of peritoneal cytology and intraoperative liver biopsies was evaluated in a subgroup of 15 patients. Patient division by stage according, respectively, to UICC and JPS classifications was: stage I: 28 and 2 patients; stage II: 12 and 11 patients; stage III: 29 and 30 patients; stage IV: 5 and 31 patients. Median survival by UICC stages was: 17 months (m) in stage I, 10 m in stage II, 12 m in stage III, and 6 m in stage IV; by JPS stages it was 29 m in stage II, 14 m in stage III, and 7 m in stage IV. A radical resection was possible in 48 patients (65%); the survival was significantly worse in the nonradical resection group. The survival difference among UICC stages was not significant in a multivariate analysis with radicality, whereas among JPS stages a significant survival difference was found in both univariate and multivariate analysis. The tumor invasion of the retroperitoneal tissues and the presence of distant metastasis were indicators of a significantly worse prognosis. Lymph node involvement, tumor size, and serosal invasion had no significant effect on survival. Peritoneal cytology and liver biopsies did not provide further prognostic information. PMID- 8195640 TI - Prevalence and clinical features of chronic pancreatitis in southern India. AB - We have conducted a field study in India in the state of Kerala involving 28,567 inhabitants to determine the prevalence and clinical features of chronic pancreatitis of the tropics (CPT), an illness that is endemic in several regions of India. Selection criteria for the present study included: 1. Characteristic abdominal pain; 2. Evidence of diabetes mellitus; and 3. Evidence of malnutrition/malabsorption. A diagnosis of chronic calcific pancreatitis (CCP) was established by evidence of either 1, 2, or 3 plus X-ray evidence of pancreatic calculi. Diagnosis of noncalcifying chronic pancreatitis (NCCP) was established by 1, 2, or 3 plus an abnormal ultrasound of the pancreas and an abnormal bentiromide test. CPT was discovered among 36 individuals (prevalence 1:793). Strict entry criteria may have excluded additional cases. CPT was far advanced at the time of diagnosis in that 28 had evidence of calcification, 19 had diabetes mellitus, and 27 had an abnormal bentiromide test. The major differences from previous hospital-based studies were female predominance (male/female ratio, 1:1.8), onset of disease at an older age (mean 23.9 yr), and evidence of milder disease. We conclude that previous hospital-based reports that CPT is a severe illness with a male predominance may reflect greater access of seriously ill individuals in general and males in particular to medical care. PMID- 8195641 TI - Dose-related comparison of antibody-dependent cellular cytotoxicity with chimeric and native murine monoclonal antibody 17-1A. Improved cytolysis of pancreatic cancer cells with chimeric 17-1A. AB - Chimeric 17-1A antibody (IgG1 kappa) was constructed by linking variable region genes of murine monoclonal antibody 17-1A with genes for human kappa light chain and gamma 1 heavy-chain constant regions. This study was undertaken to compare in vitro antibody-dependent cellular cytotoxicity (ADCC) between the chimeric 17-1A (IgG1 kappa) and native murine 17-1A antibody (IgG2a kappa) with human peripheral blood mononuclear cells (PBMNC) against 7 human tumor (1 colon, 6 pancreas) cell lines. ADCC activity was measured by chromium-release assay. When freshly isolated PBMNC from healthy donors were used for effector cells, significantly higher ADCC activity of chimeric antibody compared to murine antibody at optimal antibody dose (10 micrograms/mL) and lower doses (to 0.6 micrograms/mL) was observed against tumor cells with relatively high 17-1A expression. This high ADCC activity of the chimeric antibody persisted even when freshly-isolated monocyte-depleted PBMNC was used. When interleukin-2 activated PBMNC were used, comparable increases in ADCC were observed with both chimeric and murine antibody. These results suggest that chimeric 17-1A antibody is a more effective mediator of in vitro ADCC activity with human freshly-isolated PBMNC than the native murine antibody and this may be a better choice for clinical cancer trials evaluating possible immunotherapy with monoclonal antibody. PMID- 8195642 TI - Pancreatic centroacinar cells. The regulator of both exocrine and endocrine function. AB - The relationship between pancreatic centroacinar cells (CAC), the acinar cells, and the endocrine cells was examined in fetuses and newborn Syrian hamsters histologically, immunohistochemically, and electron microscopically. Pancreatic anlage, composed of undifferentiated cells and a few alpha cells, were found at day 12, delta cells at day 13, acinar cells at day 14, and beta cells at day 15 of the gestation. Intermediate cells (hybrid cells with both zymogen and endocrine granules) were also found after day 14. In the late-gestational period and after birth, two types of acini could be distinguished: one was composed exclusively of acinar cells and the second of acinar and CAC. In the latter type, some CAC covered the surface, lateral, and basal portion of the acinar cells, which showed a relative reduction of zymogens and increased autophagic vacuoles, a finding that indicated that CAC control the zymogen release from the acinar cells. Two types of CAC were encountered: dark cells with cytoplasmic processes located on the surface of acinar cells and larger light cells located between the acinar cells. The transitional forms between the light CAC and endocrine cells were found frequently at day 15 and a day after birth. During the endocrine cell differentiation, the committed cells lost their connection to the lumen by the force of the cytoplasmic processes of the dark CAC, which then overlaid the differentiated endocrine cells. From these findings, it can be concluded that CAC control both the pancreatic exocrine secretion and endocrine cell function. PMID- 8195643 TI - Overexpression of pancreatic secretory trypsin inhibitor in pancreatic cancer. Evaluation of its biological function as a growth factor. AB - Four clones of pancreatic secretory trypsin inhibitor (PSTI)-overexpressing cells (TF-PANC clones 1, 6, 8, and 36) were established to evaluate the physiological function of PSTI secreted by cancer cells, by means of introducing a PSTI expression vector (pRSV-PSTI) into the human pancreatic adenocarcinoma cell line (PANC-1). No obvious changes were observed in the histological features of these transplanted tumors in nude mice, in the growth of TF-PANC and PANC-1, or that of 3T3 fibroblasts when cocultured with them. Addition of recombinant human PSTI to the cultured media resulted in no increase in proliferation of fibroblasts (3T3 and WI-38) or of four pancreatic cancer cell lines (PANC-1, CAPAN-I, MIAPaCa-2, and Hs766T). These results suggest that the estimation of tumor-bearing PSTI as a paracrine or autocrine growth factor in recent studies should be given careful consideration. PMID- 8195644 TI - Pancreatic cystic islet-cell tumors. Clinical and pathologic features in two cases with cyst fluid analysis. AB - Cystic islet-cell tumors are rare neoplasms that may be confused with more familiar cystic pancreatic lesions, such as pseudocysts, serous cystadenoma, and mucinous tumors. Analysis of aspirated cyst fluid for tumor markers (carcinoembryonic antigen [CEA], CA-125, and CA-15.3), enzymes (amylase and lipase), viscosity, and cytology has been proposed as an aid to preoperative differential diagnosis. These tests will distinguish mucinous from nonmucinous cysts and usually help in determining malignancy. However, cyst fluid parameters from rarer types of pancreatic cystic tumors have not been described. We report the clinical and pathologic features of two cystic islet-cell tumors including cyst fluid parameters in one of the cases. Two cases of cystic islet-cell tumors were identified by clinical history, histopathologic, and immunohistochemical techniques. Cyst fluid was aspirated intraoperatively from one case and analyzed for CEA, CA-125, CA 15.3, insulin, amylase, viscosity, and cytology. Cyst fluid analysis showed low values for CEA, CA-125, and CA-15.3, low viscosity, and variable amylase content. This spectrum of findings is similar to that of serous cystadenomas. Cyst fluid cytologic examination was positive for neuroendocrine type epithelial cells and insulin levels were elevated, observations indicative of an islet-cell tumor. Analysis of fluid from cystic islet-cell tumors may aid in the preoperative differentiation of these tumors from more common pancreatic cystic lesions. These findings represent the first report of the characteristics of the fluid in these uncommon tumors. PMID- 8195645 TI - Munchausen syndrome by proxy: neurological manifestations. AB - Munchausen syndrome by proxy (MSP) is a recently described form of child abuse in which a caregiver fabricates or induces symptoms in a child in order to attract medical attention. The epidemiology, clinical features, diagnosis and the spectrum of MSP are reviewed. Central nervous system symptoms are a common presentation of MSP because they can be reported without confirmation. Three cases are reported to illustrate the most common neurological manifestations. It is important for neuroscience nurses to have an awareness that MSP can present as a neurologic problem, because appropriate management depends on early identification and treatment. PMID- 8195646 TI - Closed head injury assessment and research methodology. AB - About two million Americans incur head injuries each year, resulting in approximately 50,000 chronic disabilities. Several methods are currently used to determine the physiological changes underlying behavioral sequelae commonly associated with closed head injuries. Structural assessment techniques, including lesion studies, standard radiographs, computed tomography and magnetic resonance imaging, are used to determine the physical integrity of brain structures. Functional assessment techniques, including neuropsychological methods, the electroencephalograph, evoked potentials and positron emission tomography, are used to examine the brain through an analysis of its behavioral, electrical and chemical outputs. Accurate head injury assessment is vital for diagnosis, treatment planning and research. Injuries are commonly divided into the categories of mild, moderate and severe based on duration and depth of coma and the length of posttraumatic amnesia. Application of these severity assessment parameters is currently being improved through the use of standardized assessment measures. PMID- 8195647 TI - Laser and ultrasound technology in aggressive management of central nervous system tumors. AB - Tumors within the brain and spinal cord can have far-reaching effects on the health and long-term survival of the patient. In addition, implications of the diagnosis place stress upon the family unit. Until recently, aggressive management of these lesions carried the risk of additional neurological injury. With the rapidly expanding use of lasers, ultrasonic aspiration and real-time intraoperative ultrasonography, it is possible to aggressively resect tumors from within critical areas of the central nervous system, including the spinal cord. Additionally, it is possible to provide real-time evaluation of the operative field to assess tumor volume definition and completeness of tumor resection. This minimizes the risk of surgical injury and leads to improved patient outcomes. PMID- 8195648 TI - Central pontine myelinolysis: a multidisciplinary approach to care. AB - Central pontine myelinolysis (CPM) is a neurological disorder with a variety of manifestations which may be fatal or result in permanent disabilities. Various factors, most commonly too rapid correction of serum sodium, have been implicated in the development of this osmotic demyelinating syndrome. The patient's survival depends on accurate assessment and prompt intervention by the neuroscience nurse. Optimal outcome depends on collaboration by all members of the health care team. PMID- 8195650 TI - Retrograde jugular catheter: monitoring SjO2. AB - The use of the retrograde catheter in daily practice is still under investigation. Most promising is the use of continuous SjO2 monitoring. This catheter may help direct the treatment provided to patients, allowing individual needs to be met by matching perfusion to metabolism. PMID- 8195649 TI - EEGs in cognitive stages of Alzheimer's-type dementia. AB - The purpose of this study was to evaluate electroencephalogram (EEG) changes in various stages of dementia of the Alzheimer's type (DAT) through comparison with normal persons of the same age and gender. The study included 20 patients with DAT in four cognitive stages as defined by the Global Deterioration Scale (GDS) and a control group of 20 age- and gender-matched individuals without DAT. The EEGs were recorded using a Grass Model C7 Polygraph instrument and analyzed for number of alpha, beta, delta and theta waves in four leads. Statistical analysis included two-way analysis of variance (ANOVA), multiple linear regression and profile analysis. Alpha and theta waves were significant when comparing persons with DAT and control participants (p = 0.05). Delta waves were significant for group, gender and lead placement (p = 0.012). Linear regression showed a high significance between cognitive stage of the participant and alpha (p = 0.000), theta (p = 0.000) and delta (p = 0.005) waves. PMID- 8195651 TI - Betaseron: the new MS treatment. AB - Betaseron is a new medication that decreases the frequency and severity of exacerbations in persons with relapsing-remitting MS. It is the first to alter the disease itself and has, therefore, generated considerable hope among patients, families and health care providers. Patients who meet the criteria for use of Betaseron will be confronted with a number of decisions and cost factors. Further, they must be willing to prepare and administer Betaseron injections. Potential adverse effects, direct and indirect costs of Betaseron, and administration and monitoring requirements determine the nursing implications. To provide optimum care and education to patients with MS, nurses must maintain current knowledge about this new medication. PMID- 8195652 TI - Recruitment and retention of the older adult into research studies. AB - Recruitment and retention of the older adult participant presents challenges. Unless the researcher is attuned to the physical, mental and psychosocial characteristics and issues unique to the older adult population, major problems may occur. When working with an older adult population, the researcher must be aware of the changes consistent with normal aging often complicated by chronic disease states, as well as the special concerns of respondent burden, informed consent, transportation, negotiations with gatekeepers, physician involvement and common recruitment issues. Recruitment and retention must be addressed by researchers in the proposal stage of the research protocol. Techniques are available to overcome the barriers. PMID- 8195653 TI - Intravenous immunoglobulin: implications for use in the neurological patient. AB - The efficacy of intravenous immunoglobulin (IVIG) in the treatment of the autoimmune disease, idiopathic thrombocytopenic purpura (ITP), has been well documented in the literature. This has encouraged researchers to examine possible therapeutic uses of IVIG in other immune-mediated disorders. Recent clinical reports have suggested that IVIG may have a role in the treatment of neurological disorders with a possible immunopathogenic etiology. Intravenous immunoglobulin, a blood product which contains immunoglobulin G and a trace amount of immunoglobulin A, is believed to work as an immunomodulating agent. However, its mechanism of action is not well understood. Nurses involved with the administration of IVIG must be well informed about the manufacturing and regulation, proper dose and administration, adverse effects, appropriate assessments and related patient education. PMID- 8195654 TI - Decision making in high dependency environments--can we learn from modern industrial management models? AB - Increasing complexity and increased restraints affect the task of patient management in High Dependency Environments, which has become intricate and difficult. Medical knowledge alone is not enough any longer for proper patient care. Management ability and facilities are required. Current medical knowledge should be expanded by management methods and techniques. By looking at management models in the industry, we found striking similarities between the industrial management situation and clinical patient management. Both systems share complexity in structure, complexity in interaction and evolutionary character. Clinical patient management can be compared with a navigation process. The patient is steered by a control system, and course information is given by control dimensions. Clinical patient management becomes a succession of steering activities influenced by the surrounding systems. This system can be structured in three interacting layers: an operational level, in which information is collected and actions executed; a strategic level in which strategies based on goal-oriented mental anticipation of a probabilistic system are formulated; and a normative level at which principles and norms are defined. It is possible then, to define the tools which have to be developed and implemented to improve clinical management capabilities. At the operational level these tools are addressed to improve clinical decision making by providing information in an ergonomical way. They include artifact elimination, data reduction, increase in meaningful information and unwanted data filtering. At the strategic level, tools to check the feasibility of the applied strategies have to be developed, such as: ideal patient course plots and increased training in strategic thinking.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195655 TI - Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation. AB - OBJECTIVE: Before a patient can be connected to a mechanical ventilator, the controls of the apparatus need to be set up appropriately. Today, this is done by the intensive care professional. With the advent of closed loop controlled mechanical ventilation, methods will be needed to select appropriate start up settings automatically. The objective of our study was to test such a computerized method which could eventually be used as a start-up procedure (first 5-10 minutes of ventilation) for closed-loop controlled ventilation. DESIGN: Prospective Study. SETTINGS: ICU's in two adult and one children's hospital. PATIENTS: 25 critically ill adult patients (age > or = 15 y) and 17 critically ill children selected at random were studied. INTERVENTIONS: To stimulate 'initial connection', the patients were disconnected from their ventilator and transiently connected to a modified Hamilton AMADEUS ventilator for maximally one minute. During that time they were ventilated with a fixed and standardized breath pattern (Test Breaths) based on pressure controlled synchronized intermittent mandatory ventilation (PCSIMV). MEASUREMENTS AND MAIN RESULTS: Measurements of airway flow, airway pressure and instantaneous CO2 concentration using a mainstream CO2 analyzer were made at the mouth during application of the Test-Breaths. Test-Breaths were analyzed in terms of tidal volume, expiratory time constant and series dead space. Using this data an initial ventilation pattern consisting of respiratory frequency and tidal volume was calculated. This ventilation pattern was compared to the one measured prior to the onset of the study using a two-tailed paired t-test. Additionally, it was compared to a conventional method for setting up ventilators. The computer-proposed ventilation pattern did not differ significantly from the actual pattern (p > 0.05), while the conventional method did. However the scatter was large and in 6 cases deviations in the minute ventilation of more than 50% were observed. CONCLUSIONS: The analysis of standardized Test Breaths allows automatic determination of an initial ventilation pattern for intubated ICU patients. While this pattern does not seem to be superior to the one chosen by the conventional method, it is derived fully automatically and without need for manual patient data entry such as weight or height. This makes the method potentially useful as a start up procedure for closed-loop controlled ventilation. PMID- 8195656 TI - Assessment of chemical lumbar sympathectomy in critical limb ischaemia using thermal imaging. AB - Objective assessment of chemical lumbar sympathectomy (CLS) is lacking. Its success is usually judged in terms of the patient's clinical improvement. We have thermographically measured the immediate temperature changes of the lower limb following CLS using a thermal imager (SAN-EI Thermotracer 6T61). Seven patients with critical limb ischaemia and one patient with Raynaud's phenomenon underwent unilateral ablation of the lumbar sympathetic chain using 5% phenol. Four patients were diabetic, two of whom had undergone previous sympathectomy on the same side. Within fifteen minutes of injection, all patients showed a rise in skin temperature in parts of the sock distribution of between 0.8 degrees C and 8.5 degrees C. We conclude that the haemodynamic effects of CLS are immediate and can be objectively measured with thermal imaging. PMID- 8195657 TI - PC-based differential model fitting as a support for clinical research. AB - A PC-based minimisation software written in C-language is described, which solves numerically both simple non-linear regression problems and problems expressed as systems of (unsolved) initial-value ordinary or partial differential equations. The software uses second-order iterated Runge-Kutta algorithm to approximate numerically the solution curves. It uses a quasi-Newton algorithm to minimize either sums of squares (weighted or unweighted) or NONMEM loss functions. Inverse Hessian approximation to the parameter dispersion and Monte Carlo generation of artificial samples are offered to test the robustness of the parameter values obtained. A real test problem is described, involving the hydrolysation of plasma Medium Chain Triglycerides to Free Fatty Acids and the uptake of these from plasma. Two competing models were evaluated, one involving linear terms for each transfer and one involving carrier-mediated, rate-limited hydrolysis and tissue absorption steps. The simpler linear model was found to be more robust and eventually used to describe the experimental data. PMID- 8195658 TI - The effect of atropine on the T-wave amplitude of ECG during isoflurane anaesthesia. AB - The effect of bolus dose of atropine (20 micrograms kg-1) on the R/T-wave amplitude ratio of electrocardiogram was studied in 12 patients during isoflurane anaesthesia at electroencephalogram burst suppression level (mean ET of isoflurane 1.8 vol-%). The amplitude ratio was measured before, 1, 2, 5 and 10 min after atropine. Change was measured as decibels and 95% confidence intervals were calculated. The amplitude of T-wave flattened significantly after atropine. It is concluded, that the ECG T-wave amplitude reflects the balance of sympathetic and parasympathetic nervous activity during isoflurane anaesthesia. The use of the decibel transformation and confidence intervals seems to be a relevant method to interpret changes in physiologic measures during anaesthesia. PMID- 8195659 TI - A new experimental approach for monitoring postoperative bypass patency after coronary artery bypass grafting. AB - Little information is known concerning hemodynamic parameters of bypass grafts after open heart surgery during the postoperative period. As there is no easy to use bedside-method for monitoring, we developed a new implantable Doppler probe to measure blood flow velocity with a 20 MHz pulsed Doppler system. The accuracy of this method was proved in a circulatory model and in animal studies. Our conclusion is that the implantable pulsed Doppler system is a sensitive method for monitoring small vessel hemodynamics. PMID- 8195660 TI - Evaluation of a portable prototype to analyze heart rate variability. AB - Power spectrum analysis of heart rate fluctuations provide a quantitative noninvasive means of assessing the functioning of the cardiovascular control system. Until now the equipment used to study heart rate variability (HRV) have been complicated systems utilized mostly in research centers. Simpler systems are needed for routine clinical application. We have evaluated, through clinical practice, the usefulness of prototype equipment which allows acquisition and analysis of ECG signals by a portable electrocardiograph and a personal computer in which sophisticated software is installed. We performed one hundred forty-five recordings in twenty-two patients admitted to ICU. With this technique two different predictive patterns were detected: one concerning survivors, the other concerning nonsurvivors. Reliability, portability, simplicity and quality results are the main advantages of the system. The disadvantage is that it is difficult to perform HRV analysis in patients with ECG arrhythmia. This is because the program does not allow the choice of an arrhythmia-free section of the tachogram to analyze. PMID- 8195662 TI - In-house medical personnel scheduler: a computerized on-call scheduling program. AB - Creating an on-call schedule for health care professionals can be a time consuming and thankless task. We have created a computer program to reduce the time consumed when creating and correcting a call schedule and to reduce complaints about perceived call inequalities. PMID- 8195661 TI - Computer assisted detection of REM and non-REM sleep for analysis of nocturnal hypoxaemia in patients with ventilatory impairment. AB - A computer-assisted method for the evaluation of sleep and breathing in patients showing chronic ventilatory impairment is described and validated. Signals of body and respiratory movements (static charge sensitive bed), air-flow (thermistors), oxygen saturation (SaO2), electro-oculography (EOG), and electromyography (EMG) were recorded overnight and analysed. Using the compressed output graphs of the data and a rapid scoring procedure, stages of wakefulness, non-REM (stages S1-S4) and REM sleep were identified. The procedure allowed analysis of oxygen saturation data separately for each sleep stage. For validation of the method, the sleep stages identified were compared with traditional sleep staging based on a simultaneous recording of EEG, EMG and EOG in 10 patients with chronic obstructive pulmonary disease (COPD) and in 15 patients treated by thoracoplasty (TPL) for pulmonary tuberculosis. The recordings were performed in a patient ward. In total, 32 night recordings were analysed. In the COPD patients, the sensitivity and specificity of the new method were 87% and 84% in detecting non-REM sleep, and 72% and 87% in detecting REM sleep, respectively. In the TPL patients, the sensitivity and specificity were 93% and 89% with respect to non-REM sleep, and 92% and 94% in regard to REM sleep. The new method and traditional sleep staging provided closely similar quantitative estimates of the degree of sleep stage-(REM and non-REM) dependent arterial oxygen desaturation. It is concluded that the computer-assisted method, which is considerably less time consuming than traditional polysomnography, is reliable in studying sleep-related oxygenation in patients with chronic lung diseases. PMID- 8195663 TI - ECG of the month. The autonomic connection. Ventricular repolarization abnormalities. PMID- 8195665 TI - From the Committee on Pediatric Health. Mandatory screening of newborns for hearing impairment is now law in Louisiana. PMID- 8195664 TI - Perilymphatic fistulas. AB - Perilymphatic fistula (PLF) is an abnormal connection between the inner ear and middle ear space which allows the escape of perilymph and may result in disorders of hearing, balance, or both. This entity has received considerable attention and is a major area of interest and controversy in modern otology. The clinical manifestations of this condition are variable and encompass the whole spectrum of audiovestibular signs and symptoms. The diagnostic criteria have yet to be established. Currently there is no consistent objective preoperative test to diagnose PLF. Definitive diagnosis is made on middle ear exploration and rests on the observation of the surgeon. There is no objective intraoperative test to confirm the presence of PLF. The purpose of this paper is to present the classification system and current understanding of the pathogenesis of PLF. In addition, clinical manifestations, evaluation, and management of patients with this otologic entity will be reviewed. PMID- 8195666 TI - Health system reform and the paradox of autonomy. PMID- 8195667 TI - One normal angiogram is not always diagnostic after subarachnoid hemorrhage: case report and review of the literature. AB - How many angiograms should be obtained after subarachnoid hemorrhage if the first one fails to identify an aneurysm? We recently encountered this common clinical problem: a patient with subarachnoid hemorrhage confirmed by computed tomography required three angiograms to identify an aneurysm at the posterior communicating artery. Review of the literature reveals conflicting recommendations as to proper management of this common and sometimes perplexing problem. Decision-making must be applied on a case-by-case basis, but persistence is probably warranted when the index of suspicion is high. PMID- 8195668 TI - Sodium bromide acts as a contrast material on DEXA scanning. AB - Subjects undergoing a series of procedures to determine body composition, including dual-energy x-ray absorptiometry (DEXA) scanning and extracellular water volume determination by bromide dilution, demonstrated abnormal DEXA scans in some cases. Oral doses of sodium bromide in the stomach were detected on total body DEXA scanning as contrast material. The physical principles that cause bromide to be imaged in a manner similar to calcium by the DEXA scanner are discussed so that other investigators may be aware of this potential pitfall in body composition analysis. PMID- 8195669 TI - Are chylomicron remnants involved in the atherogenesis of insulin-dependent diabetes mellitus? PMID- 8195670 TI - Role of insulin resistance and hyperinsulinemia in development of hypertension and atherosclerosis. PMID- 8195671 TI - The esophageal mucosal resistance: structure and function of an unique gastrointestinal epithelial barrier. AB - The purpose of this review is to delineate the factors that contribute to the innate epithelial resistance of the esophageal mucosa when challenged with potentially damaging intraluminal aggressive factors that are present as a result of gastroesophageal reflux. The ability of this mucosa to act as an effective barrier is dependent on the structural complexity of its 20 to 30 cell layer thick stratified squamous epithelia, its convoluted intercellular spaces (paracellular resistance), and the cellular ion transport mechanisms that maintain intracellular homoestasis (cellular resistance). Because H+ ion is the most important damaging agent in the gastroesophageal refluxate, we have primarily focused on mechanisms that impede or prevent H+ ion entry into the mucosa ("pre-epithelial" and "mucosal factors"), cellular mechanisms that allow cells to maintain their intracellular pH in the presence of an external acid environment ("cellular factors"), mechanisms that limit continued mucosal and cellular injury ("submucosal factors") and reparative processes that come into play after damage has occurred. PMID- 8195673 TI - Interleukin-1 regulation of collecting duct prostaglandin E2 and cyclic nucleotide accumulation. AB - Interleukin-1 (IL-1) causes a diuresis and natriuresis in experimental animals. The natriuresis is due, at least in part, to IL-1 stimulation of prostaglandin E2 (PGE2) synthesis by the inner medullary collecting duct (IMCD), with resultant inhibition of Na(+)-K(+)-adenosine triphosphatase activity. It is unknown whether IL-1 affects other signal transduction systems in the IMCDs that regulate nephron sodium and water reabsorption. Furthermore, indirect evidence suggests that IL-1 inhibits sodium and water transport in other nephron segments. Consequently we examined (1) the effect of IL-1 on cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) accumulation by rat IMCD cells and (2) IL-1 stimulation of signal transduction mechanisms throughout the nephron. IL-1 had no affect on cGMP or arginine vasopressin-dependent (AVP-dependent) or isoproterenol dependent cAMP accumulation in cultured rat IMCD cells. IL-1 increased PGE2 levels in rabbit IMCD, cortical collecting tubule (CCT), and to a lesser extent, medullary thick ascending limb cells, but had no effect on proximal tubule cells. IL-1 also did not alter AVP-dependent cAMP accumulation in the CCT. The failure of IL-1 to reduce AVP responsiveness in the CCT was not due to culture conditions, because AVP-dependent cAMP accumulation in freshly isolated CCT cells was also not affected by the cytokine but was inhibited by exogenous PGE2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195672 TI - Effects of subcutaneous recombinant human erythropoietin in normal subjects: development of decreased reticulocyte hemoglobin content and iron-deficient erythropoiesis. AB - The present study evaluates the properties of the reticulocytes produced in healthy volunteers after treatment with different regimens of recombinant human erythropoietin (r-HuEPO). Twenty-four subjects were randomly assigned to one of three different subcutaneous (SC) r-HuEPO (Protcrit; Ortho Biotech) administration protocols (I: 300 U/kg on days 1, 4, 7, 10; II: 400 U/kg on days 1, 5, 9; III: 600 U/kg on days 1, 10) with oral iron supplementation (Niferex; 150 mg, twice a day). The characteristics of the reticulocytes produced were examined with a flow cytometry method that allows measurements of individual reticulocyte cell volume, hemoglobin concentration, and hemoglobin content. Administration of SC r-HuEPO was associated with a significant increase in the production of reticulocytes. The hemoglobin content of reticulocytes (CHr, in picograms of hemoglobin per cell) in the three groups was 28.5 +/- 1.0, 28.2 +/- 0.5, and 28.5 +/- 1.3, respectively, at baseline, decreased to 24.6 +/- 1.6 (p < 0.001), 24.5 +/- 2.3 (p < 0.001), and 27.5 +/- 1.8 (not significant) at day 10, and returned to baseline after r-HuEPO was discontinued (28.8 +/- 0.9, 28 +/- 0.8, and 28.8 +/- 1.4, respectively, at day 22). The percentage of reticulocytes with cell hemoglobin content less than 23 pg was taken as an indicator of iron deficient erythropoiesis. At baseline, 5.6% +/- 2.7%, 6.9% +/- 3.4%, and 8.3% +/- 3.8% of reticulocytes had less than 23 pg hemoglobin in groups I, II, and III, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195674 TI - Maturational response of colonic and renal Na+,K(+)-ATPase activity to K+ load and betamethasone in preterm rats. AB - Preterm human infants demonstrate high fecal K+/Na+ ratio that is inversely related to maturation. Renal and colonic basolateral membrane-located Na+,K(+) adenosine triphosphatase (Na+,K(+)-ATPase) governs K+ excretion and is enhanced by both steroid administration and K+ loading. However, the response of premature kidney or colon to these stimuli is not well studied. We measured basal as well as stimulated levels of renal and colonic Na+,K(+)-ATPase activity in response to betamethasone and K+ load given separately and betamethasone given after K+ load in premature, mature, and 4-day-old Sprague-Dawley rats. Although preterm rats showed a higher basal level in the kidneys (p < 0.004), an increase in enzyme activity in response to the stimuli was achieved only in the colon (p < 0.001 for betamethasone, p < 0.0001 for K+ load, and p < 0.0007 for the combination). At term and at 4 days of postnatal age, however, the kidneys showed much higher levels than the colon in response to stimuli (p < 0.0001 for all) except for betamethasone at term. The response of colonic tissue of preterm and term rats to betamethasone given 4 days after a K+ load was less marked than response to betamethasone or K+ load given separately (p < 0.001). The stimulated levels achieved in the preterm colon were higher than the basal preterm renal values (p < 0.001). The tissue K+ content increased in response to K+ load in only the preterm colon (p < 0.05). We have demonstrated a tissue specificity in the development of Na+,K(+)-ATPase activity in K+ excretory organs of rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195675 TI - Early adhesion of bacteremic strains of Staphylococcus epidermidis to polystyrene: influence of hydrophobicity, slime production, plasma, albumin, fibrinogen, and fibronectin. AB - Twenty bacteremic strains of Staphylococcus epidermidis were characterized according to their hydrophobicity, their ability to produce slime, and their in vitro adhesion to polystyrene microtiter plates precoated or not with plasma proteins. Four strains of Staphylococcus aureus were also tested for adhesion. Slime production in S. epidermidis was not correlated with initial adhesion, whether measured qualitatively or by a quantitative method. Hydrophobicity (xylene:water partition) was well correlated with adhesion. Slime production, adhesion, and hydrophobicity were highly strain dependent among S. epidermidis organisms. For S. epidermidis, early adhesion was inhibited (10% to 98%) by albumin and fibronectin in all strains, by plasma (19 strains), and by fibrinogen (18 strains). Stimulation occurred for one strain with plasma and two strains with fibrinogen. In contrast, adhesion was inhibited by albumin and markedly stimulated (twofold to 14-fold) by plasma, fibrinogen, and fibronectin for the four strains of S. aureus. Early adhesion of S. epidermidis to polymer surface appears to depend mainly on hydrophobicity and is usually impaired by plasma proteins, albumin, fibrinogen and fibronectin; with a heterogeneous behavior among the different strains tested. Slime production would interpose secondarily, after the first attachment. PMID- 8195676 TI - Diaspirin cross-linked hemoglobin: tissue distribution and long-term excretion after exchange transfusion. AB - This report describes the tissue distribution and long-term (14-day) excretion of hemoglobin cross-linked between the alpha-chains (alpha alpha Hb) with carbon 14 labeled bis(3,5-dibromosalicyl)fumarate. Fully conscious, chronically cannulated rats (n = 40) were treated with a 50% isovolemic exchange transfusion (ET) with solutions of 14C-labeled alpha alpha Hb (8.0 gm/dl) and were then monitored for as long as 14 days. Thirteen tissue types were analyzed for radioactivity by liquid scintillation counting. The highest concentration of label was found in the kidney and in tissues of the reticuloendothelial system (i.e., spleen, bone marrow, and liver). The 14C-labeled alpha alpha Hb did not appear to cross the blood-brain barrier, because radioactivity in the brain was barely detectable. The dose of 14C-labeled alpha alpha Hb (2.4 gm Hb/kg) produced an initial plasma Hb level of 4.6 gm/dl, with a half-life in the plasma of 5.0 hours. The peak concentration in kidney, spleen, and liver occurred at 24 hours after ET, when at least 92% of the 14C-labeled alpha alpha Hb in plasma had been cleared. At 48 hours, red casts were seen in a tiny number of renal tubules in some rats. By 14 days, up to 64% of the injected radioactivity had been recovered in urine and about 10% was recovered in feces. Most excretion occurred 24 to 48 hours after ET. This study demonstrated that 2 weeks were required for the metabolic degradation and elimination of a large dose of alpha alpha Hb in rats. PMID- 8195677 TI - Latex allergy: frequent occurrence of IgE antibodies to a cluster of 11 latex proteins in patients with spina bifida and histories of anaphylaxis. AB - Proteins and allergens in natural rubber latex were characterized by a two dimensional immunoblot method with serum samples from 17 patients with latex allergy of whom 10 had spina bifida and 7 were health care workers. We demonstrated in rubber tree sap approximately 240 polypeptides of which 57 bound immunoglobulin E (IgE) in patient serum samples. Forty-six of the 57 allergens were identified by patients with spina bifida, 19 of 57 allergens by health care workers, and 8 of 57 allergens by both patient groups. IgE antibodies from all 5 patients with spina bifida with histories of anaphylaxis bound three allergens with molecular weights of 27 kd and isoelectric points ranging from pH 4.6 to pH 4.8. Four of these 5 patients also identified a complex of eight other allergens with molecular weights ranging from 13 kd to 27 kd and isoelectric points from pH 4.4 to pH 5.6. This cluster of 11 allergens was identified by none of the 7 health care workers and by only 1 of 5 patients with spina bifida without demonstrable anaphylaxis. These preliminary findings indicate that patients with spina bifida in whom latex hypersensitivity has developed exhibit a strong anti latex IgE immune response, which seems to differ markedly from the immune response of health care workers with latex allergy. The characteristic anti-latex IgE profile in patients with spina bifida and with a history of an anaphylactic reaction may be valuable in the evaluation of pathogenetic processes in latex allergy. PMID- 8195678 TI - Analysis of elevated serum interleukin-6 levels in rheumatoid arthritis: correlation with erythrocyte sedimentation rate or C-reactive protein. AB - The purpose of this study was to determine whether selected antirheumatic drugs would suppress elevated circulating interleukin-6 (IL-6) levels in patients with rheumatoid arthritis (RA). The 267 patients who enrolled in a double-blind randomized protocol received placebo, naproxen (1500 mg/day), or prinomide (1500 mg/day) for up to 16 weeks. Serum samples from 143 of the patients completing the trial and from 135 normal donors were analyzed by quantitative sandwich enzyme linked immunosorbent assay for IL-6 concentrations. A mean normal IL-6 value was determined to be 3 pg/ml (95th percentile value = 10 pg/ml). IL-6 levels at baseline for the patients with RA were significantly higher than those for control subjects (p < 0.0001). Elevated IL-6 levels (> 10 pg/ml) at baseline were found in 80% of subjects with RA (median = 36 pg/ml, range 12 to 403). For patients with elevated levels of either IL-6, C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR) at baseline, initial median values of IL-6, CRP, and ESR were compared with those from the final visit for each treatment group. There was no significant decrease in IL-6 levels with treatment. Median CRP levels decreased significantly, from 1.9 to 0.8 mg/dl (p = 0.002), as did median ESR (37 to 34 mm/hr, p = 0.013), only in the prinomide-treated group. PMID- 8195679 TI - Measurement of membrane phospholipid asymmetry in normal and sickle-cell erythrocytes by means of annexin V binding. AB - We investigated the use of annexin V (placental anticoagulant protein I), a calcium-dependent protein that binds tightly to phosphatidylserine-containing membranes, as a means to measure membrane phospholipid asymmetry in human erythrocytes. Iodine 125-labeled annexin V bound to erythrocytes in a specific, reversible, calcium-dependent reaction (dissociation constant = 25 +/- 4 nmol/L at 37 degrees C and 2.5 mmol/L calcium). Lysed erythrocytes contained 1.2 x 10(6) binding sites for annexin V. Treatment of erythrocytes with 1 mumol/L A23187 in the presence of 2.5 mmol/L calcium at 37 degrees C caused a gradual but marked increase in annexin V binding sites, reaching a level of approximately 300,000 sites per cell after 8 hours of incubation. We also noted a very gradual spontaneous exposure of annexin V binding sites during storage of purified erythrocytes, reaching a level of approximately 20,000 sites per cell after 30 days. Measurements could also be made directly on diluted whole blood specimens. In samples freshly drawn from 35 normal donors, a mean number of 276 sites per cell were present; this increased to 858 sites per cell after storage of specimens at 4 degrees C for 24 hours. Measurement of annexin V binding to samples from patients with sickle-cell anemia revealed a marked increase in binding (mean of 12,430 sites per cell for all samples); serial measurements in a patient hospitalized with sickle-cell crisis showed a progressive decline in annexin V binding over a period of 6 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195680 TI - Aspergillus ribotoxins react with IgE and IgG antibodies of patients with allergic bronchopulmonary aspergillosis. AB - Asp f I has been identified as a major allergen of Aspergillus fumigatus and shows amino acid sequence homology with the mitogillin family of cytotoxins. In this study we compared the various cytotoxins from Aspergillus species for their reactivity with immunoglobulin E (IgE) and immunoglobulin G (IgG) antibodies in the serum samples of patients with allergic bronchopulmonary aspergillosis. Elevated levels of IgE and IgG antibodies to all A. fumigatus antigens and ribotoxins were demonstrated in a majority of ABPA patients as compared with allergic patients with asthma and normal subjects. In approximately 75% of patients with allergic aspergillosis, IgE antibody to ribotoxins showed marked elevation, whereas in the remaining patients it was below the baseline, although crude A. fumigatus antigen showed higher specific serum IgE. These results suggest that cytotoxins play a major role in the pathogenesis of allergic bronchopulmonary aspergillosis. PMID- 8195681 TI - The interaction of artemisinin with red cell membranes. AB - Artemisinin (qinghaosu) and its derivatives are endoperoxide-containing compounds that are an important new class of antimalarial drugs. Tritiated dihydroartemisinin is taken up and concentrated by isolated red cell membranes but not by intact erythrocytes. More than half of the membrane-associated drug can be released by treatment with phospholipase A2 followed by extraction with ethyl acetate. The remaining drug appears to be bound to the major red cell membrane proteins. There is no association of the drug with either the membrane or cytoplasm of intact red cells. Thus dihydroartemisinin appears to be taken up by isolated membranes, where it associates with proteins but not via intact red cells. PMID- 8195682 TI - Effects of enalapril on endothelin-1 and growth factor gene expression in diabetic rat glomeruli. AB - We have previously reported that the mRNA levels of endothelin (ET-1), tumor necrosis factor-alpha), (TNF-alpha), platelet-derived growth factor (PDGF)-B chain, transforming growth factor (TGF-beta), and basic fibroblast growth factor (bFGF) all increased with age in diabetic rat glomeruli. We have now assessed the effect of the angiotensin-converting enzyme inhibitor enalapril on the expression of the ET-1, TNF-alpha, PDGF-B, TGF-beta, and bFGF genes in 24-week-old rat glomeruli after streptozotocin injection. Animals were divided into controls, enalapril-treated diabetic rats, and untreated diabetic rats. Treatment continued for 24 weeks. Enalapril reduced both creatinine clearance (p < 0.001) and urinary protein excretion (p < 0.01) in diabetic rats. Enalapril produced a nonsignificant 15 mm Hg reduction in blood pressure in diabetic rats. Enalapril also attenuated the increases in ET-1 mRNA levels observed in the glomeruli of diabetic rats (0.5-fold compared with untreated diabetic rats at 24 weeks [p < 0.01]) but had no effect on increased mRNA levels of TNF-alpha, PDGF-B, TGF-beta, and bFGF. These findings suggest that enalapril therapy may be effective in reducing ET-1 mRNA expression in the glomeruli of diabetic nephropathy. PMID- 8195683 TI - Effects of clodronate (dichloromethylene bisphosphonate) on the development of experimental atherosclerosis in rabbits. AB - The effects of clodronate, a bisphosphonate for the treatment of hypercalcemia, on the progress of atherosclerosis were studied in rabbits fed with a high cholesterol (1%) diet and treated simultaneously with disodium clodronate 0 (saline), 1, 5, or 25 mg/kg intravenously twice a week for 6, 9, and 12 weeks. In 9 to 12 weeks, plasma total cholesterol increased from 0.8 +/- 0.3 mmol/L (mean +/- SD) in rabbits fed the standard diet to 46 +/- 17 mmol/L in animals subjected to high-cholesterol diet. Clodronate did not influence the cholesterol concentration in plasma. None of the parameters studied were changed by clodronate within 6 weeks after beginning the treatment. In 9 to 12 weeks (n = 7 to 9), plasma total Ca++ concentration was decreased from 3.55 +/- 0.12 mmol/L in the saline group to 3.36 +/- 0.16 mmol/L in the group on the greatest clodronate dose (p < 0.05). Free and esterified cholesterol and total Ca++ concentrations in the wall of thoracic aorta were reduced by the greatest dose of clodronate, compared with the groups treated with saline solution or smaller doses of the drug (p < 0.05). At 12 weeks, the greatest dose of clodronate also reduced the visible and lipid-stained atheromatous areas in the thoracic and abdominal aorta, compared with those in the saline and the other clodronate dose groups (p < 0.05). The results suggest that a high dose of clodronate inhibits the development of diet-induced atherosclerosis in rabbits. PMID- 8195684 TI - Side effects induced by gold drugs: a graft-versus-host-like disease. PMID- 8195685 TI - beta-Lactamase-positive Staphylococcus epidermidis (CNS3017) no longer that organism. PMID- 8195686 TI - The effects of learning strategy instruction on the completion of job applications by students with learning disabilities. AB - The purpose of this study was to assess the effects of learning strategy instruction on the completion of job applications by students identified as learning disabled. Thirty-three students (average age 15 years 6 months) were randomly assigned by grade and gender to one of two experimental conditions: learning strategy instruction or traditional instruction. The result was 16 students (10 boys and 6 girls) being placed under the learning strategy instruction condition and 17 students (10 boys and 7 girls) being placed under the traditional instruction condition. Results indicated that in addition to statistically significant lower numbers of information omissions and information location errors, holistic ratings of the overall neatness of the job applications were significantly higher for those students under the learning strategy instruction condition. In addition to these positive changes in the performance measures, social validity data suggest that students under the learning strategy condition would be more likely to receive an invitation for a job interview. The findings and future research needs are discussed. PMID- 8195688 TI - Subtypes of learning disabilities in adolescents and adults. AB - This study tested the hypothesis that a classification scheme developed for the subtyping of learning disabilities in children, when applied to a population of adolescents and adults, would result in subtyping into discrete and relatively homogeneous groups in terms of cognitive functioning and achievement. We compared three groups, arithmetic disability (AD), reading disability (RD), and reading and arithmetic disabilities (RAD), among themselves and with a comparison group with normal achievement (NA) on a variety of cognitive and achievement measures. The main findings were as follows: (a) Each of the groups differed significantly from the others on tests of reading, spelling, memory, and other cognitive measures; (b) both the RD and RAD groups showed a deficit in phonological processing, vocabulary, spelling, and STM; (c) the AD group performed similarly to the NA group on pseudoword reading and phonological processing, but did more poorly than the NA group on word reading and vocabulary; (d) on many tasks the RAD group performed more poorly than the other groups; and (e) the AD and RAD groups performed more poorly than the NA and RD groups on a visual-spatial task. This study demonstrated the validity of this classification scheme for the subtyping of learning disabilities in adolescents and adults. PMID- 8195687 TI - The effects of early bilateral otitis media with effusion on educational attainment: a prospective cohort study. AB - The relationship between long-lasting, bilateral otitis media with effusion (OME) between the ages of 2 and 4 and educational attainment, in particular, reading and spelling ability at 7 years of age, was studied in a prospective cohort study of 946 children. After selection, three groups were distinguished: 151 children with long-lasting, bilateral OME at preschool age, 37 preschool children treated with ventilation tubes, and 82 children with no history of OME at that age. Early bilateral OME was found to affect spelling ability, but not reading ability, at 7 years. The effects of OME did not appear to increase with the number of observations of OME. Also, recurrent hearing loss did not have more detrimental effects than continuous hearing loss. Effects of treatment with ventilation tubes were not found. Only the teachers' ratings of writing ability indicated a slight advantage of treatment with ventilation tubes. In conclusion, the educational consequences of early OME appear to be very small. PMID- 8195689 TI - Referral-to-placement ratio: a finding in need of reassessment? PMID- 8195690 TI - Using self-recording, evaluation, and graphing to increase completion of homework assignments. AB - This article describes the use of self-monitoring procedures to increase the number of daily homework assignments completed by eight students with learning disabilities. Students ranged in age from 13 to 16 years and attended Grades 7 through 10. The experimental procedure involved the use of a sheet listing all daily assignments given by regular classroom teachers. A multiple-baseline design across subjects demonstrated a clear relationship between the introduction of self-monitoring of assignments and an increase in assignments completed. Goal setting and self-graphing of data appeared to increase this effect. PMID- 8195691 TI - When academic assistance is not enough: addressing the mental health issues of adolescents and adults with learning disabilities. AB - This article focuses on an answer to a critical question for adolescents and adults with learning disabilities: How can professionals assist students with learning disabilities who have psychosocial issues that appear to be affecting their academic progress and life adjustment? Inherent in this inquiry are other, equally important issues, such as: How do learning disabilities service providers know when to involve other service providers? What are the steps in referring a student for further assistance with different mental health issues? When are team interventions necessary? How are team interventions conducted in either secondary or postsecondary settings? How should learning disabilities service providers establish the boundaries of their professional expertise and/or responsibilities to adequately meet the needs of individuals with learning disabilities? This article illustrates answers to these questions by providing examples of interventions and case studies from two federally funded research/demonstration projects at the University of Minnesota: the Learning Disabilities Transition Project and Project Extra. The authors describe theoretical models for mental health services that address the psychosocial issues frequently encountered in academic or vocational settings. Recommendations are also included that discuss how the models can be personalized to fit the reader's home institution or agency. PMID- 8195692 TI - The road not taken: an integrative theoretical model of reading disability. AB - This article describes a theoretical model of reading disability that integrates a wide range of research findings in cognitive psychology, reading, and education across the age and grade span. The model shows how reading disability relates to normal reading acquisition, and includes four possible patterns of reading disability: nonalphabetic readers, compensatory readers, nonautomatic readers, and readers delayed in the acquisition of word-recognition skills. We compare our model to the models of other investigators and argue that our model is especially useful to practitioners. Finally, we discuss some of the educational implications of the model. PMID- 8195693 TI - Remodeling of the plasma membrane after stimulation of neutrophils with f-Met-Leu Phe and dihydrocytochalasin B: identification of membrane subdomains containing NADPH oxidase activity. AB - Superoxide (O2-) production by neutrophils stimulated with chemotactic peptides [e.g., formylmethionyl-leucyl-phenylalanine (fMLP)] is transient but increases in rate and duration after pretreatment of the cells with dihydrocytochalasin B (dhCB), suggesting a possible role for the plasma membrane and membrane skeleton in the regulation of the O2- generating system. Analysis of plasma membrane isolated from these cells by isopycnic sucrose density gradient sedimentation showed that there were no significant variation in the distribution of plasma membrane markers between control and dhCB-treated cells, whereas a significant redistribution of plasma membrane markers was observed in dhCB + fMLP-treated cells. Instead of sedimenting to 31-35% sucrose, as in the former two groups, plasma membrane markers were broadly distributed over 25-50% sucrose in the dhCB + fMLP-treated cells. In addition, approximately 80% degranulation was achieved in these cells, whereas little granule release (< 5%) was observed in control and dhCB-treated cells. Analysis of the gradient fractions for membrane skeletal (actin and fodrin) and NADPH oxidase (cytochrome b and p47-phox) components in dhCB + fMLP-treated cells demonstrated that the distribution of fodrin, actin, cytochrome b, and p47-phox followed the broad distribution of plasma membrane markers, with an overall eightfold increase in membrane-associated actin. Despite the broad redistribution of plasma membrane markers, the distribution of O2- generating activity remained confined to a narrower peak at approximately 50% sucrose. These results demonstrate that a heterogeneous surface membrane of higher density with a differential distribution of proteins and O2- generating activity are created after dhCB + fMLP treatment; however, domain structure is conserved in the new membrane, with only a subfraction of the reorganized plasma membrane containing all of the components necessary for active O2- generation. Our results support a role for plasma membrane lateral organization and participation of the membrane skeleton in the regulation of the O2- generating system. PMID- 8195694 TI - Interferon-gamma inhibits tumor antigen presentation by epidermal antigen presenting cells. AB - Murine I-A+ epidermal antigen-presenting cells (APCs) have been shown to be capable of presenting soluble tumor fragments (TFs), as a source of tumor associated antigens (TAAs), for primary and secondary tumor immune responses. In this study we investigated whether incubation of epidermal APCs in interferon gamma (IFN-gamma) modulates their ability to present TAA and whether the effects of IFN-gamma on the presentation of tumor antigen correspond to its effects on alloantigen presentation in both primed and unprimed systems. Our results show that three weekly subcutaneous injections of naive mice with GM-CSF-cultured but not with fresh TAA-pulsed epidermal APCs induce protective tumor immunity in naive mice and that the immunostimulatory effect of GM-CSF in this system is abrogated by coculture of epidermal cells in IFN-gamma. Furthermore, epidermal APCs are able to present TAA to primed, tumor-immune mice, as assessed by the elicitation of tumor-specific delayed-type hypersensitivity after injection of TAA-pulsed epidermal APCs. IFN-gamma was found to inhibit tumor antigen presentation by freshly prepared epidermal APCs in this system. The effects of IFN-gamma on the presentation of tumor antigen correlated well with its effects on the primary and secondary mixed epidermal cell-lymphocyte reaction, indicating that IFN-gamma differentially modulates the function of epidermal APCs with regard to induction versus elicitation of immunity. PMID- 8195695 TI - Temporal down-regulation of Fc gamma RIII expression and Fc gamma receptor mediated phagocytosis in human monocyte-derived macrophages induced by TNF-alpha and IL-1 beta. AB - Effects of tumor necrosis factor (TNF-alpha) and interleukin-1 beta (IL-1 beta) on the expression of Fc gamma receptors (Fc gamma Rs) and on Fc gamma R-mediated phagocytosis in human monocyte-derived macrophages (MDMs) have been determined. Treatment of MDMs with TNF-alpha (400 pg/ml) or IL-1 beta (400 pg/ml) for 80 min decreased cell surface Fc gamma RIII expression, as measured by flow cytometry (FACS), while the levels of surface Fc gamma RI and Fc gamma RII remained unchanged. Surface Fc gamma RIII expression remained depressed for 7 h after exposure of MDMs to either cytokine but then rose progressively until, by 24 h of stimulation, the levels were at least as high as those on unstimulated cells. In parallel with cell surface Fc gamma RIII levels, phagocytosis of immunoglobulin G opsonized fluorescent beads, as measured by FACS, decreased and then increased over time after stimulation of MDMs with TNF-alpha while the opsonin-independent phagocytic activity was unchanged, suggesting that among the three classes of Fc gamma receptors on macrophages, Fc gamma RIII may play a critical role in regulating opsonic phagocytosis. After treatment with IL-1 beta, both opsonic and nonopsonic phagocytic activities of MDMs were significantly decreased, regardless of Fc gamma RIII levels. FACS analysis of rhodamine-phalloidin-stained MDMs showed that after incubation with IL-1 beta, but not TNF-alpha, the content of F actin declined in MDMs, coinciding with inhibition of particle phagocytosis. Rapid down-regulation and subsequent recovery of macrophage Fc gamma RIII expression following cytokine stimulation could serve as a novel regulatory mechanism employed by inflammatory cells in host defense. PMID- 8195696 TI - The cooperative effects of TNF-alpha and IFN-gamma are determining factors in the ability of IL-10 to protect mice from lethal endotoxemia. AB - Recent studies have demonstrated that interleukin-10 (IL-10) has the capacity to protect mice from the lethal effects of endotoxin. In this investigation, we have examined the ability of IL-10 to protect both normal mice and Corynebacterium parvum-primed mice against endotoxin lethality. In the overwhelming majority of experiments, recombinant murine IL-10 (rMuIL-10) and recombinant human IL-10 (rHuIL-10) did not protect normal BALB/cJ mice from lipopolysaccharide (LPS) induced lethality at doses up to 10 micrograms/mouse. Despite their inability to protect, both IL-10 preparations were highly effective in preventing the increase in serum tumor necrosis factor alpha (TNF-alpha) that occurred in response to the lethal dose of LPS. Moreover, a neutralizing antibody against TNF-alpha gave only partial protection when administered alone to BALB/cJ mice. Treatment with a combination of neutralizing antibodies against TNF-alpha and interferon-gamma (IFN-gamma) resulted in complete protection. In contrast to BALB/cJ mice, normal BDF1 mice were protected from lethal endotoxemia by treatment with both rMuIL-10 and rHuIL-10. However, IL-10 did not protect C. parvum-primed BDF1 against LPS lethality even though it caused a reduction in the LPS-induced serum TNF-alpha response in C. parvum-primed mice as well as in normal BDF1 mice. Neutralizing antibodies against TNF-alpha and IFN-gamma were protective when administered alone to normal BDF1 mice, as previously demonstrated in C. parvum-primed mice. These findings suggest that lethal endotoxemia is a result of the cooperative activities of TNF-alpha and IFN-gamma in normal mice of the BALB/cJ and BDF1 strains as well as in C. parvum-primed BDF1 mice. IL-10 appears to be less effective in protecting mice from lethal endotoxemia when cooperation between IFN gamma and TNF-alpha is facilitated by high-level production of the cytokines as in C. parvum-primed mice or when there is evidence of strong synergy between them as in normal BALB/cJ mice. PMID- 8195697 TI - In vivo administration of a monoclonal antibody against the type I IL-1 receptor inhibits the ability of mice to eliminate Mycobacterium paratuberculosis. AB - The purpose of this study was to determine the influence of endogenous interleukin-1 (IL-1) on resistance to paratuberculosis infection in experimentally infected gnotobiotic mice. Following a 6-month treatment with prednisolone to facilitate bacillary multiplication, control mice substantially reduced the numbers of M. paratuberculosis in the liver and ileum. In contrast, mice injected with a monoclonal antibody against the type I IL-1 receptor failed to reduce the numbers of M. paratuberculosis in the liver and ileum and exhibited more liver granulomas, which contained numerous acid-fast bacilli. These results indicate a significant role for endogenous IL-1 in host defense against experimental M. paratuberculosis infection in mice. PMID- 8195698 TI - Blockade of liver macrophages by gadolinium chloride reduces lethality in endotoxemic rats--analysis of mechanisms of lethality in endotoxemia. AB - We investigated the effects of gadolinium chloride (GdCl3.6H2O), which blocks phagocytosis by liver macrophages, on the mortality, blood tumor necrosis factor (TNF) levels, and hepatotoxicity in a lethal endotoxic shock rat model system [10 mg/kg body weight lipopolysaccharide (LPS) intravenously]. With administration of GdCl3, twice at 0.5 or 5 mg/kg, the survival rate 24 h after LPS injection was 56% and 100%, respectively, whereas the level of TNF in blood was not affected. Microscopic investigation of the liver revealed that the focal necrosis of hepatocytes under endotoxemia was completely protected by the administration of GdCl3 at 5 mg/kg. We then investigated the effects of GdCl3 on superoxide (O2-) production by isolated liver macrophages in vitro. The O2- production by liver macrophages isolated from control rats was suppressed by GdCl3 in a dose dependent manner. GdCl3 also had a cytotoxic effect on these macrophages. The enhanced O2- production by liver macrophages isolated from sublethal endotoxemic (1 mg/kg) rats was suppressed by pretreatment with GdCl3 (5 mg/kg). It was suggested that lethality in endotoxemia cannot be explained only by the degree of increase in blood TNF levels and that the mechanism by which GdCl3 reduces mortality and hepatotoxicity in endotoxemia possibly includes suppression of superoxide production by liver macrophages. PMID- 8195699 TI - Relationship between phagosome acidification, phagosome-lysosome fusion, and mechanism of particle ingestion. AB - The fate of pathogens ingested by macrophages is dependent on phagosome acidification and fusion with different intracellular vesicles. Whereas the mode of particle recognition by the phagocyte seems the main determinant of phagosome lysosome fusion, the influence of membrane reorganization, fusion events, and cell activation in phagosome acidification is not well known. We looked for a relationship between the nature of receptors involved in phagocytosis, phagosome acidification, and phagosome-lysosome fusion. Murine macrophage-like P388D1 cells were made to ingest sheep erythrocytes coated with immunoglobulin G (EIgG) or IgM and complement (EIgMC) or treated with glutaraldehyde and periodate (EGP). The following results were obtained: (1) As expected, the adhesion of the three particle types was differentially inhibited by monoclonal antibodies specific for Fc gamma RII and CD11b/CD18. (2) The phagosomes containing all three particle types displayed similar acidification kinetics with a pH decrease to 6 within the first 10 min after ingestion. (3) Only phagosomes containing EIgG or EIgMC were fused with peroxidase-loaded secondary lysosomes. (4) Coating EGP with IgG only partially restored fusion, even when the surface density of IgG was markedly higher than found on EIgG. It is concluded that phagosome acidification and fusion are regulated by different mechanisms. Also, the lack of fusion observed with EGP is not entirely accounted for by the absence of stimulation of suitable receptors on the phagocyte membrane, because it cannot be restored by providing such a stimulus. PMID- 8195700 TI - Endotoxin and GM-CSF-mediated down-regulation of macrophage apo E secretion is inhibited by a TNF-specific monoclonal antibody. AB - Macrophage activation is associated with increased secretion of monokines, proteases, arachidonic acid metabolites, reactive oxygen, and nitrogen intermediates and yet decreased secretion of apolipoprotein E (apo E). Although the kinetics of apo E down-regulation have been investigated, the mechanism(s) involved remains unknown. In the present study, the question of whether macrophage-activating factors such as lipopolysaccharide (LPS) and granulocyte macrophage colony-stimulating factor (GM-CSF) directly result in apo E down regulation or indirectly by inducing the secretion of other inflammatory mediators has been investigated. LPS-stimulated macrophages demonstrated a dose dependent reduction in apo E secretion with a 70% decrease occurring following a 48-h incubation with 20 ng/ml LPS. Coculture of these cells with a neutralizing concentration of a hamster monoclonal antibody against murine tumor necrosis factor (TNF) inhibited the LPS-mediated reduction in apo E secretion. This inhibitory effect resulting from TNF neutralization was not observed using pooled hamster immunoglobulin G, or hamster monoclonals against murine interleukin-1 alpha (IL-1 alpha), IL-1 beta, or interferon-gamma. Similar results were observed when GM-CSF was used to induce apo E down-regulation. The inhibitory effects of TNF neutralization on endotoxin-induced apo E down-regulation were dependent on LPS concentration and were no longer apparent at concentrations greater than 200 ng/ml. These results suggest that an autocrine, TNF-dependent mechanism may play a role in the down-regulation of apo E secretion during macrophage activation. PMID- 8195701 TI - Role of the mevalonate pathway of isoprenoid synthesis in IL-8 generation by activated monocytic cells. AB - The highly regulated enzyme HMG-CoA reductase generates mevalonate, the precursor of a complex series of isoprenoids that posttranslationally modify (isoprenylate) certain proteins (e.g., the low-molecular-weight GTP-binding proteins) or that are incorporated into cholesterol and other end products. We recently reported that isoprenoids are required for NADPH oxidase activity in granulocytes via LMW GTP-binding protein isoprenylation. In this study, we evaluated the effects of isoprenoid depletion on the expression of proinflammatory genes in human monocytic THP-1 cells. We selected conditions under which pretreatment for 24 h with isoprenoid synthesis inhibitors (HMG-CoA reductase inhibitor lovastatin or compactin at 10 microM) did not compromise cell viability but markedly suppressed H2O2 generation. Under these conditions interleukin-8 (IL-8) production was attenuated (by 50-90%) in response to lipopolysaccharide, granulocyte-macrophage colony-stimulating factor, and phorbol myristate acetate. Coincubation of reductase inhibitor-treated cells with mevalonate prevented the attenuation of IL 8 production by reductase inhibitors. The effects of isoprenoid depletion on cytokine production were selective: IL-1 beta generation was not inhibited but the production of IL-6 and IL-8 was concomitantly suppressed. IL-8 induction was suppressed at least in part through attenuation of the increase in mRNA in stimulated cells. We conclude that isoprenoid generation through the mevalonate pathway is a requirement for IL-8 induction by activated monocytic cells in vitro. Isoprenylation inhibitors have the potential to alter monocyte proinflammatory function. PMID- 8195702 TI - Monomer-dimer equilibria of interleukin-8 and neutrophil-activating peptide 2. Evidence for IL-8 binding as a dimer and oligomer to IL-8 receptor B. AB - By chemical cross-linking experiments we show that at physiologically relevant concentrations IL-8 and NAP-2 monomers are in an equilibrium with dimers and even oligomers (KD approximately 300-800 nM). Oligomerization seems to be more prevalent for IL-8 than for NAP-2. The form in which IL-8 and NAP-2 bind to their specific receptors was analyzed in binding experiments with COS-1 cells expressing IL-8 receptor A or B in recombinant forms. Both receptors were cloned from the human myeloid leukemic cell line AML-193. Type A receptor had high affinity for IL-8 (KD approximately 4 nM) and low affinity for NAP-2 (KD > or = 700 nM), whereas the type B receptor was of equally high affinity (KD approximately 2 nM) for both IL-8 and NAP-2. However, IL-8 receptor B could bind specifically three to four times more IL-8 than NAP-2, and NAP-2 was a weak competitor for IL-8 binding to the same receptor. In addition, IL-8, but not NAP 2, could be cross-linked to dimers when bound to IL-8 receptor B. We suggest from these findings that IL-8, but not NAP-2, binds as a dimer and oligomer to IL-8 receptor. PMID- 8195703 TI - Synthetic polysulfated hyaluronic acid is a potent inhibitor for tumor necrosis factor production. AB - Based on the premise that naturally occurring glycosaminoglycans could serve as building blocks for synthesizing nontoxic drugs for suppression of tumor necrosis factor (TNF) production by inflammatory cells, we have chemically modified hyaluronic acid (HA) and tested its effects in blocking TNF-alpha and TNF-beta production in vitro. HA was chosen mainly for its structural simplicity, nonimmunogenicity, and readiness for chemical modifications. When HA was chemically polysulfated to a sulfate/hexosamine molar ratio of 3.9, the sulfated HAs was shown to be a potent inhibitor of TNF-alpha production in lipopolysaccharide (LPS)- or interferon-gamma-activated THP-1 cells. For example, a concentration of HAs as low as 10 ng/ml reduced TNF-alpha production in LPS activated THP-1 cells more than 50%, whereas achieving a similar extent of reduction required 50 micrograms/ml native HA. By decreasing the extent of polysulfation, the inhibitory effect of HAs on TNF-alpha production was diminished. Other chemical modifications, including deacetylation, thiolation, or reduction of the carboxylic groups, could not increase the efficacy of HA in suppression of TNF-alpha production. Naturally polysulfated glycosaminoglycans, such as chondroitin sulfates, keratan sulfate, heparan sulfate, and heparin, failed to inhibit TNF-alpha production. HAs also restricted TNF-beta (lymphotoxin) secretion in an Epstein-Barr virus-transformed B cell line, Roha-9, which constitutively produces TNF-beta. HAs had no inhibitory effect on the proliferation of THP-1 or Roha-9 cells, which would account for the reduced TNF alpha or TNF-beta production. Furthermore, time-course metabolic labeling studies revealed that HAs could not restrict overall protein synthesis and secretion in THP-1 cells. However, HAs increased complement C1q secretion in THP-1 in a dose dependent manner, but it had no effect on biosynthesis of complement C1 inhibitor, factor D, and Fc gamma receptor type II (Fc gamma RII). These results indicate that HA, selectively restricts the production of TNF-alpha, TNF-beta, and probably several other protein species. PMID- 8195704 TI - Generation of an ovine bone marrow-derived myelomonocyte-like cell line by retroviral-mediated transformation. Immunological characterization and the effect of cytokines and lipopolysaccharides. AB - A cell line (designated BMpXT1) was generated from sheep bone marrow using the Moloney murine leukemia virus-based retroviral vector pXT1. BMpXT1 cells resembled mature alveolar macrophages in being adherent and esterase positive, in expressing certain cell surface antigens, and in secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) when stimulated by ovine interferon-gamma and lipopolysaccharide (LPS) in combination. The absence of a proliferative response to ovine GM-CSF and macrophage colony-stimulating factor, the absence of other cell antigens found in mature macrophages, and low-efficiency phagocytosis suggested that the cells may be at an intermediate to late stage of myelomonocytic differentiation. PMID- 8195705 TI - HOCl production by human neutrophils activated by surface-associated IgG: requirement for influx of extracellular calcium. AB - Neutrophils produce large quantities of HOCl when stimulated by surface associated immunoglobulin G, a result not seen when neutrophils are stimulated with soluble complexes of IgG. Compared with unactivated cells or cells stimulated with soluble aggregates of IgG, a significant influx of extracellular 45Ca2+ was observed in cells activated by surface-associated IgG. Removal of extracellular calcium with EGTA almost completely blocked HOCl production. Similarly, treatment of neutrophils with lanthanum, which has been shown to interfere with calcium channels, also effectively blocked HOCl production. These results were not secondary to an overall decrease in activation, as superoxide production and release of the specific granule protein lactoferrin and the azurophilic granule protein myeloperoxidase were not significantly altered by lanthanum or EGTA. Production of H2O2, the precursor of HOCl, was similarly decreased by both EGTA and lanthanum. Induction of extracellular calcium influx with a calcium ionophore in the presence of soluble aggregates of IgG resulted in HOCl production. Production of HOCl is not sensitive to inhibition by pretreatment of cells with pertussis toxin. These observations indicate that the differences in the biological responses of human neutrophils to surface associated IgG compared with soluble aggregates of IgG are associated with differing signaling events, including influx of extracellular calcium. PMID- 8195706 TI - Role of Fc gamma receptors in cancer and infectious disease. AB - Receptors for the Fc domain of immunoglobulin G (Fc gamma R) provide an interface between specific humoral immunity and the cellular branch of the immune system through their interaction with antibody. Cross-linking Fc gamma R on myeloid cells triggers such diverse functions as clearance of immune complexes, phagocytosis of opsonized pathogens, secretion of reactive oxygen intermediates, and antibody-dependent cellular cytotoxicity. The Fc gamma R play a major role in the removal of antibody-coated infectious agents and are the exclusive trigger molecules for tumor cell killing by human myeloid cells. Studies of Fc gamma R function have been aided by the use of Fc gamma R specific monoclonal antibodies, self-directed target cells, and bispecific antibodies that link target cells or pathogens to specific host cell molecules, including Fc gamma R. These reagents have contributed significantly to our understanding of the role of the different classes of Fc gamma R in mediating protection from various infectious agents and in mediating tumor cell killing. Taken together, these approaches have provided insight into the utility of manipulating Fc gamma R function in the therapy of cancer and infectious disease. PMID- 8195707 TI - Understanding the dendritic cell lineage through a study of cytokine receptors. AB - Dendritic cells form a system of antigen presenting cells that are specialized to stimulate T lymphocytes, including quiescent T cells. The lineage of dendritic cells is not fully characterized, although prior studies have shown that growth and differentiation are controlled by cytokines, particularly granulocyte/macrophage colony-stimulating factor (GM-CSF). To further elucidate the nature and control of the dendritic cell lineage, we have studied the expression of specific cytokine receptors. Sufficient numbers of dendritic cells were purified from spleen and skin to do quantitative binding studies with radiolabeled M-CSF, GM-CSF, and interleukin 1 (IL-1). To verify the nonlymphoid nature of dendritic cells, we made an initial search for rearrangements in T cell receptor and immunoglobulin genes and none were found. M-CSF binding sites, a property of mononuclear phagocytes, also were absent. In contrast, GM-CSF receptors were abundant on mature dendritic cells, with approximately 3,000 binding sites/cell with a single Kd of 500-1,000 pM. Substantial numbers of high affinity (< 100 pM) IL-1 binding sites were identified as well; cultured epidermal dendritic cells (i.e., epidermal Langerhans cells) had 500/cell and spleen dendritic cells approximately 70/cell. Cross-linking approaches showed the 80-kD species that is expected of high-affinity type 1 IL-1 receptor. Anti-type 1 IL-1 receptor (R) mAbs also visualized these receptors by flow cytometry on freshly isolated epidermal dendritic cells. These results provide new evidence that dendritic cells represent a differentiation pathway distinct from lymphocytes and monocytes. Together with recent findings on the effects of IL-1 and GM-CSF on epidermal dendritic cells in situ (see Results and Discussion), the data lead to a proposal whereby IL-1 signals IL-1R to upregulate GM-CSF receptors and thereby, the observed responsiveness of dendritic cells to GM-CSF for growth, viability, and function. PMID- 8195708 TI - Interleukin 7-dependent B lymphocyte precursor cells are ultrasensitive to apoptosis. AB - We have compared the sensitivity of clonogenic interleukin 7 (IL-7)-dependent murine B cell precursors with that of clonogenic mature B cells and myeloid precursors to alpha-particles from plutonium-238 and X radiation. All three populations are relatively sensitive, but B cell precursors are ultrasensitive. This differential sensitivity is also observed with corticosteroid, etoposide, and cisplatin, all apoptosis-inducing drugs used in the treatment of leukemia and other cancers. Further, we show that x-rays and drugs induce the bulk of the B cell precursor population to undergo rapid apoptosis, despite the continued presence of IL-7. B cell precursors were found to express very low levels of BCL 2 protein compared with mature splenic B cells and their resistance to x-rays and corticosteroid could be enhanced by expression of a BCL-2 transgene. These data have important implications for normal lymphopoiesis and for the behavior of leukemic lymphoid precursor cells. PMID- 8195709 TI - Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular "heads" of C1q. AB - This work describes the functional characterization, cDNA cloning, and expression of a novel cell surface protein. This protein designated gC1q-R, was first isolated from Raji cells and was found to bind to the globular "heads" of C1q molecules, at physiological ionic strength, and also to inhibit complement mediated lysis of sheep erythrocytes by human serum. The NH2-terminal amino acid sequence of the first 24 residues of the C1q-binding protein was determined and this information allowed the synthesis of two degenerate polymerase chain reaction primers for use in the preparation of a probe in the screening of a B cell cDNA library. The cDNA isolated, using this probe, was found to encode a pre pro protein of 282 residues. The NH2 terminus of the protein isolated from Raji cells started at residue 74 of the predicted pre-pro sequence. The cDNA sequence shows that the purified protein has three potential N-glycosylation residues and is a highly charged, acidic molecule. Hence, its binding to C1q may be primarily but not exclusively due to ionic interactions. The "mature" protein, corresponding to amino acid residues 74-282 of the predicted pre-pro sequence, was overexpressed in Escherichia coli and was purified to homogeneity. This recombinant protein was also able to inhibit the complement-mediated lysis of sheep erythrocytes by human serum and was shown to be a tetramer by gel filtration in nondissociating conditions. Northern blot and RT-PCR studies showed that the C1q-binding protein is expressed at high levels in Raji and Daudi cell lines, at moderate levels in U937, Molt-4, and HepG2 cell lines, and at a very low level in the HL60 cell line. However, it is not expressed in the K562 cell line. Comparison of gC1q-R NH2-terminal sequence with that of the receptor for the collagen-like domain of C1q (cC1q-R) showed no similarity. Furthermore, antibodies to gC1q-R or an 18-amino acid residue-long NH2-terminal synthetic gC1q R peptide did not cross-react with antibodies to cC1q-R. Anti-gC1q-R immunoblotted a 33-kD Raji cell membrane protein, whereas anti cC1q-R recognized a molecule of approximately 60 kD. The NH2-terminal sequence of gC1g-R appears to be displayed extracellularly since anti-gC1g-R peptide reacted with surface molecules on lymphocytes, polymorphonuclear leukocytes, and platelets, as assessed by flow cytometric and confocal laser scanning microscopic analyses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8195710 TI - Propagation of dendritic cell progenitors from normal mouse liver using granulocyte/macrophage colony-stimulating factor and their maturational development in the presence of type-1 collagen. AB - Within 1 wk of liquid culture in granulocyte/macrophage colony-stimulating factor (GM-CSF), normal B10 BR (H-2k I-E+) mouse liver nonparenchymal cells (NPC) formed loosely adherent myeloid cell clusters that have been shown to contain dendritic cell (DC) progenitors in similar studies of mouse blood or bone marrow. Mononuclear cell progeny released from these clusters at and beyond 4 d exhibited distinct dendritic morphology and were actively phagocytic. After 6-10 d of culture, these cells strongly expressed CD45, CD11b, heat stable antigen, and CD44. However, the intensity of expression of the DC-restricted markers NLDC 145, 33D1, and N418, and the macrophage marker F4/80, intercellular adhesion molecule 1, and Fc gamma RII was low to moderate, whereas the cells were negative for CD3, CD45RA, and NK1.1. Splenocytes prepared in the same way also had a similar range and intensity of expression of these immunophenotypic markers. Unlike the splenic DC, however, most of the GM-CSF-propagated putative liver DC harvested at 6-10 d expressed only a low level of major histocompatibility complex (MHC) class II (I Ek), and they failed to induce primary allogeneic responses in naive T cells, even when propagated additionally in GM-CSF and tumor necrosis alpha and/or interferon gamma-supplemented medium. However, when 7-d cultured GM-CSF stimulated liver cells were maintained additionally for three or more days on type-1 collagen-coated plates in the continued presence of GM-CSF, they exhibited characteristics of mature DC: MHC class II expression was markedly upregulated, mixed leukocyte reaction stimulatory activity was increased, and phagocytic function was decreased. Similar observations were made when Ia+ cells were depleted from the GM-CSF-propagated cells before exposure to collagen. Further evidence that the GM-CSF-stimulated class IIdim or class II-depleted hepatic NPC were immature DC was obtained by injecting them into allogeneic B10 (H-2b I-E-) recipients. They "homed" to T cell-dependent areas of lymph nodes and spleen where they strongly expressed donor MHC class II antigen 1-5 d later. These observations provide insight into the regulation of DC maturation, and are congruent with the possibility that the migration of immature DC from normal liver and perhaps other organ allografts may help explain their inherent tolerogenicity. PMID- 8195711 TI - Steroid production in the thymus: implications for thymocyte selection. AB - The mouse thymus was assessed for its ability to produce steroids. Cultured thymic non-T cells produced soluble pregnenolone and deoxycorticosterone, and immunohistochemistry demonstrated steroidogenic enzymes in radioresistant thymic epithelial cells but not in thymocytes. Inhibition of thymic corticosterone production or blockade of the glucocorticoid receptor with RU-486 resulted in enhanced TCR-mediated, antigen-specific deletion of immature thymocytes. These data indicate that locally produced glucocorticoids, because of their antagonism of TCR-mediated signaling for death, may be a key element of antigen-specific thymocyte selection. PMID- 8195712 TI - Simultaneous expression of tissue factor and tissue factor pathway inhibitor by human monocytes. A potential mechanism for localized control of blood coagulation. AB - Cells of monocytic lineage can initiate extravascular fibrin deposition via expression of blood coagulation mediators. This report is about experiments on three mechanisms with the potential to modulate monocyte-initiated coagulation. Monocyte procoagulant activity was examined as a function of lipid cofactor, protein cofactor, and specific inhibitor expression during short-term culture in vitro. Lipid cofactor activity was measured as the initial rate of factor X activation by intrinsic-pathway components, the assembly of which depends on this cofactor. Lipid cofactor activity levels changed by < 30% during 48-h culture. Protein cofactor, i.e., tissue factor (TF) antigen was measured by enzyme immunoassay. It increased from 461 pg/ml to a maximum value of 3,550 pg/ml at 24 h and remained at 70% of this value. Specific TF activity, measured as factor VII dependent factor X activation rate, decreased from 54 to 18 nM FXa/min between 24 and 48 h. TF activity did not correlate well with either lipid cofactor or TF protein levels. In contrast, the decrease in TF activity coincided in time with maximal expression of tissue factor pathway inhibitor (TFPI) mRNA, which was determined using reverse transcriptase polymerase chain reaction (RT-PCR), and with maximal TFPI protein levels measured by immunoassay. The number of mRNA copies coding for TFPI and TF in freshly isolated blood monocytes were 46 and 20 copies/cells, respectively. These values increased to 220 and 63 copies/cell during short-term cell culture in the presence of endotoxin. Results demonstrate concomitant expression by monocytes of genes coding for both the essential protein cofactor and the specific inhibitor of the extrinsic coagulation pathway. Together with functional and antigenic analyses, they also imply that the initiation of blood clotting by extravascular monocyte/macrophages can be modulated locally by TFPI independently of plasma sources of the inhibitor. PMID- 8195713 TI - Negative regulation of p120GAP GTPase promoting activity by p210bcr/abl: implication for RAS-dependent Philadelphia chromosome positive cell growth. AB - The p210bcr/abl tyrosine kinase appears to be responsible for initiating and maintaining the leukemic phenotype in chronic myelogenous leukemia (CML) patients. p21ras-p120GAP interactions play a central role in transducing mitogenic signals. Therefore, we investigated whether p21ras and p120GAP are regulated by p210bcr/abl, and whether this activation is functionally significant for CML cell proliferation. We report that transient expression of p210bcr/abl in fibroblast-like cells induces simultaneous activation of p21ras and inhibition of GTPase-promoting activity of p120GAP, and confirm these data showing that downregulation of p210bcr/abl expression in CML cells with bcr/abl antisense oligodeoxynucleotides induces both inhibition of p21ras activation and stimulation of GTPase-promoting activity of p120GAP. Tyrosine phosphorylation of two p120GAP-associated proteins, p190 and p62, which may affect p120GAP activity, also depends on p210bcr/abl tyrosine kinase expression. Direct dependence of these effects on the kinase activity is proven in experiments in which expression of c-MYB protein in fibroblast-like cells or downregulation of c-MYB expression resulting in analogous inhibition of CML cell proliferation does not result in the same changes. Use of specific antisense oligodeoxynucleotides to downregulate p21ras expression revealed a requirement for functional p21ras in the proliferation of Philadelphia chromosome-positive CML primary cells. Thus, the p210bcr/abl-dependent regulation of p120GAP activity is responsible, in part, for the maintenance of p21ras in the active GTP-bound form, a crucial requirement for CML cell proliferation. PMID- 8195714 TI - Independent regulation of DNA recombination and immunoglobulin (Ig) secretion during isotype switching to IgG1 and IgE. AB - Induction of switch recombination to the gamma 1 and epsilon immunoglobulin (Ig) heavy chain loci was examined in B cells preactivated with anti-Ig (B lymphoblasts). In B lymphoblasts cultured with interleukin 4 (IL-4), IL-5 induced the accumulation of S micro-S gamma 1 rearrangements, but not epsilon recombination. Thus, IL-5 facilitates switch recombination directed to the gamma 1 heavy chain locus by IL-4, but additional signals are required to drive rearrangements to epsilon. Lipopolysaccharide (LPS), in the presence of IL-4, induced the accumulation of both S micro-S gamma 1 and S micro-S epsilon rearrangements, and cells treated with LPS exhibited 40-50-fold more S micro-S gamma 1 rearrangements than cells cultured with IL-5. Induction of switch recombination was not always associated with secretion of the respective Ig isotype, since concentrations of IL-4 that were sufficient to direct switch recombination to gamma 1 and epsilon in blasts treated with LPS failed to elicit secretion of IgG1 and IgE. These results demonstrate differential requirements for switch recombination to the gamma 1 and epsilon loci, as well as independent regulation of Ig gene rearrangement and secretion of each isotype. PMID- 8195715 TI - The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. AB - For over 25 years, the cytokine known as macrophage migration inhibitory factor (MIF) has been considered to be a product of activated T lymphocytes. We recently identified the murine homolog of human MIF as a protein secreted by the pituitary in response to endotoxin administration. In the course of these studies, we also detected MIF in acute sera obtained from endotoxin-treated, T cell-deficient (nude), and hypophysectomized mice, suggesting that still more cell types produce MIF. Here, we report that cells of the monocyte/macrophage lineage are an important source of MIF in vitro and in vivo. We observed high levels of both preformed MIF protein and MIF mRNA in resting, nonstimulated cells. In the murine macrophage cell line RAW 264.7, MIF secretion was induced by as little as 10 pg/ml of lipopolysaccharide (LPS), peaked at 1 ng/ml, and was undetectable at LPS concentrations > 1 microgram/ml. A similar stimulation profile was observed in LPS-treated peritoneal macrophages; however, higher LPS concentrations were necessary to induce peak MIF production unless cells had been preincubated with interferon gamma (IFN-gamma). In RAW 264.7 macrophages, MIF secretion also was induced by tumor necrosis factor alpha (TNF-alpha) and IFN-gamma, but not by interleukins 1 beta or 6. Of note, MIF-stimulated macrophages were observed to secrete bioactive TNF-alpha. Although previously overlooked, the macrophage is both an important source and an important target of MIF in vivo. The activation of both central (pituitary) and peripheral (macrophage) sources of MIF production by inflammatory stimuli provides further evidence for the critical role of this cytokine in the systemic response to tissue invasion. PMID- 8195716 TI - Involvement of 15-lipoxygenase in early stages of atherogenesis. AB - The arachidonate 15-lipoxygenase which is expressed in atherosclerotic lesions is implicated in the oxidative modification of low density lipoproteins during atherogenesis. To obtain experimental in vivo evidence for this hypothesis, we analyzed the structure of oxygenated lipids isolated from the aorta of rabbits fed with a cholesterol-rich diet for different time periods and compared the pattern of oxygenation products with that isolated from low density lipoproteins treated in vitro with the pure rabbit 15-lipoxygenase and with oxygenated lipids isolated from advanced human atherosclerotic lesions. In early atherosclerotic lesions (12-wk cholesterol feeding), specific lipoxygenase products were detected whose structure was similar to those isolated from lipoxygenase-treated low density lipoproteins. The appearance of these products did coincide with the lipid deposition in the vessel wall. In later stages of atherogenesis (26-wk cholesterol feeding) the degree of oxidative modification of the tissue lipids did increase but the share of specific lipoxygenase products was significantly lower, suggesting an increasing overlay of the specific lipoxygenase products by nonenzymatic lipid peroxidation. In advanced human atherosclerotic lesions, large amounts of oxygenation products were detected whose structure suggests a nonenzymatic origin. These data suggest that the arachidonate 15-lipoxygenase is of pathophysiological importance during the early stages of atherogenesis. In later stages of plaque development nonenzymatic lipid peroxidation becomes more relevant. PMID- 8195717 TI - Temporal and lineage-specific control of T cell receptor alpha/delta gene rearrangement by T cell receptor alpha and delta enhancers. AB - To analyze the regulation of gene rearrangement at the T cell receptor (TCR) alpha/delta locus during T cell development, we generated transgenic mice carrying a human TCR delta gene minilocus. We previously showed that the presence of the TCR delta enhancer (E delta) within the J delta 3-C delta intron was required to activate a specific step (V-D to J) of transgene rearrangement, and that rearrangement was activated equivalently in the precursors of alpha beta and gamma delta T cells. To further explore the role of transcriptional enhancers in establishing the developmental pattern of gene rearrangement at the TCR alpha/delta locus, we substituted the TCR alpha enhancer (E alpha) in place of E delta within the transgenic minilocus. We found that V-D-J rearrangement of the E alpha+ minilocus was restricted to the alpha beta T cell subset. Further, we found that although V-D-J rearrangement of the E delta+ minilocus was initiated in the fetal thymus by day 14.5, V-D-J rearrangement of the E alpha+ minilocus did not occur until fetal day 16.5. Finally, whereas V-D-J rearrangement of the E delta+ minilocus is essentially completed within the triple negative population of postnatal thymocytes, V-D-J rearrangement of the E alpha+ minilocus is only initiated late within this population. Since the properties of minilocus rearrangement under the control of E delta and E alpha parallel the properties of V delta-D delta-J delta and V alpha-J alpha rearrangement at the endogenous TCR alpha/delta locus, we conclude that these enhancers play an important role in orchestrating the developmental program of rearrangements at this locus. PMID- 8195718 TI - Cross-reactivities in memory cytotoxic T lymphocyte recognition of heterologous viruses. AB - Analyses of the relationships between different viruses and viral proteins have focused on homologies between linear amino acid sequences, but cross-reactivities at the level of T cell recognition may not be dependent on a conserved linear sequence of several amino acids. The CTL response to Pichinde virus (PV) and vaccinia virus (VV) in C57BL/6 mice previously immunized with lymphocytic choriomeningitis virus (LCMV) included the reactivation of memory cytotoxic T lymphocyte (CTL) specific to LCMV. Limiting dilution assays (LDA) demonstrated that at least part of this reactivation of memory cells in LCMV-immune mice related to cross-reactivity at the clonal level, even though acute infections with these viruses in nonimmune mice elicited CTL responses that did not cross react in conventional bulk CTL assays. Precursor CTL (pCTL) to LCMV were generated in splenic leukocytes from LCMV-immune mice acutely infected with PV or VV when stimulated in vitro with only the second virus but not with uninfected peritoneal exudate cells (PECs). Cytotoxicity mediated by LCMV-specific CTL clones activated by PV infection was greatly inhibited by anti-CD8 antibody, suggesting that these memory CTL clones recognizing LCMV-infected targets were of low affinity. LCMV-immune splenocytes stimulated in vitro with PV or VV demonstrated a low but significant precursor frequency (p/f) to the heterologous viruses, and splenocytes from PV- or VV-immune mice when stimulated in vitro against LCMV generated a low but significant p/f to LCMV. Short-term CTL clones cross-reactive between LCMV and PV were derived from splenic leukocytes from LCMV immune mice acutely infected with PV. To distinguish whether the cross-reactivity was directed against a viral peptide or a virus-induced endogenous cellular neoantigen, we demonstrated that a pCTL frequency to PV about 1/4-1/7 that of the frequency to LCMV could be generated from LCMV-immune splenic leukocytes stimulated with the immunodominant LCMV NP peptide. A partially homologous PV peptide generated from the equivalent site to the LCMV NP peptide did not sensitize targets to lysis by either LCMV- or PV-specific CTLs, suggesting that the cross-reactivity in killing was not due to evolutionarily conserved equivalent sequences. Experiments also indicated that prior immunity to one virus could modulate future primary immune responses to a second virus. Elevated pCTL frequencies to PV were seen after acute PV infection of LCMV-immune mice, and elevated pCTL frequencies to LCMV were seen after acute LCMV infection of PV- and VV-immune mice.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8195719 TI - CD3+CD16+NK1.1+B220+ large granular lymphocytes arise from both alpha-beta TCR+CD4-CD8- and gamma-delta TCR+CD4-CD8- cells. AB - Cultivation of CD4-CD8- double negative (DN) mouse thymocytes and splenocytes with recombinant interleukin 2 (IL2) in the absence of other stimulation results in the generation of DN-CD3/TCR+CD16+NK1.1+B220+ large granular lymphocytes (LGL). Purified DN alpha-beta TCR+ thymocytes and splenocytes are CD16+IL2R alpha IL2R beta+NK1.1+B220-CD5high. These cells are unique in that they express both CD16 and T cell receptor (TCR) which are usually mutually exclusive. In addition, they express the natural killer (NK) marker, NK1.1. Cultivation of these cells with IL2 for several days results in the generation of DN alpha-beta TCR+CD16+NK1.1+B220+CD5- LGL, suggesting that DN alpha-beta TCR+ cells in thymus and spleen are the precursors of the DN LGL reported previously. DN gamma-delta TCR+CD16-NK1.1-B220-CD5high thymocytes and splenocytes also give rise to DN gamma delta TCR+CD16+NK1.1+B220+CD5- LGL which, as shown previously with DN alpha-beta TCR+ LGL cells, are cytotoxic against NK-sensitive YAC-1 cells. Cytotoxic activity is also induced through either CD16 or the gamma-delta TCR. DN alpha beta TCR+ and DN gamma-delta TCR+ LGL cells are thus similar in phenotype to TCR- NK cells. DN alpha-beta TCR+ thymocytes express low levels of the gamma subunit of the high affinity immunoglobulin E receptor (Fc epsilon RI gamma) molecule, an essential component of CD16 expression. Fc epsilon RI gamma expression is greatly enhanced after cultivation with IL2, resulting in a higher surface expression of CD16. In contrast to DN alpha-beta TCR+ thymocytes, DN gamma-delta TCR+ thymocytes do not express detectable CD16 or Fc epsilon RI gamma mRNA but expression of both is induced by cultivation with IL2, leading to the expression of CD16 on the surface. Whereas CD16 molecules on both DN alpha-beta TCR+ and DN gamma-delta TCR+ LGL are associated with only Fc epsilon RI gamma homodimers, the TCR on these cells are associated with an Fc epsilon RI gamma homodimer and/or CD3 zeta-Fc epsilon RI gamma heterodimers. These results demonstrate that the Fc epsilon RI gamma subunit is a component of the TCR in a fraction of T lineage cells. PMID- 8195720 TI - CD4-mediated enhancement or inhibition of T cell activation does not require the CD4:p56lck association. AB - CD4 is the coreceptor molecule expressed on the surface of T cells specific for or restricted by class II molecules of the major histocompatibility complex (MHC). Its expression on T cells is required for an optimal response to antigen (Ag). Three mechanisms have been invoked for the involvement of CD4 in T cell activation. First, it was shown that CD4 binds to MHC class II molecules on antigen presenting cells (APCs) thereby favoring an adhesion between effector cells and APCs. Association of CD4 to the T cell receptor and to the tyrosine kinase p56lck have also been shown to be critically involved in the positive function of CD4. Here, we demonstrate that the interaction of CD4 with p56lck is not required to enhance the response of two CD4-dependent, Ag-specific T cell hybridomas. Mutant forms of CD4 (TCD4), which lose association to p56lck, were expressed in these T cells and were shown to enhance the Ag-specific response as efficiently as the wild-type CD4. Moreover both CD4-dependent and independent T cell responses were inhibited by CD4-specific mAbs even when CD4 was not associated with p56lck. These results indicate that mechanisms distinct from sequestration of p56lck and/or negative signaling operate in these inhibitions. Results demonstrating enhancement of TCR-mediated signaling by the coaggregation of TCD4 mutant to the TCR further confirm that the association of p56lck to CD4 is not absolutely required for the regulatory functions of CD4. Our results suggest that the mechanisms implicated in the enhancement of T cell stimulation via CD4 depend solely on the extracellular and transmembrane domains of CD4. PMID- 8195722 TI - Resting and activated T cells display different requirements for CD8 molecules. AB - Clonotype-positive (1B2+) T cells from 2C T cell receptor (TCR) transgenic mice were used to define the role of CD8 molecules in the induction phase vs. the effector phase of the primary response to class I alloantigens. Three main findings are reported. First, in the presence of exogenous lymphokines, resting CD8+ 2C cells gave strong proliferative responses to two alloantigens, Ld and Kbm11. In the absence of added lymphokines, however, CD8+ 2C cells responded only to Ld and not to Kbm11; Ld stimulated both interleukin 2 (IL-2) and IL-2 receptor (R) synthesis, whereas Kbm11 elicited only IL-2R synthesis. The primary response of CD8+ 2C cells was thus helper-independent (HI) to Ld but helper-dependent (HD) to Kbm11, presumably reflecting that Ld is a stronger antigen than Kbm11. Second, in contrast to CD8+ cells, CD8- 2C cells mounted only an HD and not an HI response to the strong Ld antigen; conversely, selecting for a minor subset of CD8hi cells enabled 2C cells to mount an HI response to the weak Kbm11 antigen. These findings, together with experiments with heterozygous vs. homozygous stimulator cells, suggest that HI and HD responses reflect differences in the overall avidity of T antigen presenting cell (APC) interaction: high-avidity interaction leads to strong intracellular signaling and an HI response, whereas low-avidity interaction causes weak signaling and an HD response; high-avidity T/APC interaction is heavily dependent on CD8 expression. Third, CD8 expression was found to be less important for CTL activity than for primary proliferative responses. Thus, in contrast to HI proliferative responses, CTL responses of 2C cells to Ld were CD8 independent. However, 2C lysis of Ld targets became strongly CD8 dependent in the presence of limiting doses of anti-TCR (1B2) antibody. Collectively, the data suggest that, both for T cell induction and the expression of effector function, CD8 molecules play a decisive role in augmenting TCR mediated signaling, either by promoting TCR contact with antigen or delivering kinases (p56lck) to the TCR/CD3 complex, or both. PMID- 8195721 TI - Restriction of interferon gamma responsiveness and basal expression of the myeloid human Fc gamma R1b gene is mediated by a functional PU.1 site and a transcription initiator consensus. AB - The restricted expression of the human Fc gamma R1b gene to myeloid cells is likely to be regulated by a combination of transcription factors that may not be solely expressed in myeloid cells, but act together to restrict the expression of the gene to myeloid cells. Low basal expression of the human Fc gamma R1b gene is specifically upregulated by interferon gamma (IFN-gamma). A 181-bp region of 5' flanking sequence contains several key regulatory motifs that include the extended gamma response region (XGRR) and the PIE region. The XGRR contains the 39-bp gamma response region originally defined in the highly homologous Fc gamma R1a gene. The XGRR is in close proximity to the 21-bp PIE motif that is conserved in the promoters of some other myeloid genes. The PIE motif contains a consensus site for the macrophage and B cell transcription factor, PU.1, and is adjacent to the cluster of transcription start sites. An active transcription initiator, Inr, consensus spans the start sites and appears to direct transcription initiation of this TATA-less gene. In this study, we demonstrate that the PIE region contains a functional PU.1 site that binds a human PU.1-like protein and that associated factors present in myeloid extracts also bind in this PIE region. Mutational analysis reveals an absolute requirement for an intact PU.1 box for both basal and IFN-gamma inducible expression of this gene. In addition, mutations in the Inr greatly reduce basal and inducible transcription. Insertion of a strong TATA box downstream from the Inr or at -30 bp from the transcription start sites restores basal and inducible activity in the presence of a mutated PU.1 site. We also demonstrate that indeed, when the XGRR is positioned in the context of a heterologous TATA containing promoter, it is able to respond equivalently to either IFN-alpha or IFN-gamma. However, IFN-alpha responsiveness does not occur in the context of the physiological Fc gamma R1b TATA-less basal promoter. Our results suggest that a human PU.1-like factor acts as a "bridging factor" between the upstream IFN-gamma enhancer and the Inr dependent preinitiation complex. These findings indicate that the structure of the basal promoter in combination with restricted activators like PU.1 are important in regulating the expression of this gene. PMID- 8195723 TI - Coordinate defects in human histocompatibility leukocyte antigen class II expression and antigen presentation in bare lymphocyte syndrome. AB - The human immunodeficiency, type II bare lymphocyte syndrome (BLS), has been attributed to a defect in the transcription of class II histocompatibility genes. Immunocompetence, as assessed by functional exogenous antigen presentation, was not restored in immortalized B cells, derived from a BLS patient, after transfection with HLA-DR class II structural genes. Incubation of protein antigens, as well as infectious virus, with DR-transfected BLS cells failed to induce activation of antigen-specific helper T lymphocytes. Peptide antigens were presented by class II molecules displayed on BLS cells, although the conformation of these class II proteins was altered as indicated by epitope mapping. This defect in antigen presentation was independent of the specific class II DR allele transfected into BLS cells. Genetic complementation analysis has been used with BLS cells to demonstrate that the defect in class II gene transcription is linked to the absence of a trans-acting factor. Similarly, functional class II dimers were restored after in vitro fusion of cells derived from two distinct BLS complementation groups, implying that specific transcriptional control elements are shared by a gene critical for antigen presentation and genes encoding HLA class II antigens. Thus, two important functionally linked pathways of class II molecules, structural gene expression and antigen presentation, share a common regulatory pathway defective in BLS. PMID- 8195724 TI - Frequency of immunoglobulin E class switching is autonomously determined and independent of prior switching to other classes. AB - Both, in humans and in mice, a major fraction of immunoglobulin E (IgE) expressing B lymphocytes develops by sequential Ig class switching from IgM via IgG to IgE. This sequential class switch might have functional implications for the frequency and repertoire of IgE+ cells. Here we show that in mutant mice, in which sequential switching to IgE via IgG1 is blocked, the frequency of cells switching to IgE is not affected. Thus, sequential class switching to IgE merely reflects the simultaneous accessibility of two acceptor switch regions for switch recombination, induced by one cytokine, but with markedly distinct efficiency. Analysis of switch recombination on both IgH alleles of switched cells shows that the low frequency of switching to IgE is an inherent feature of the S epsilon switch region and its control elements. PMID- 8195725 TI - Vancomycin dosing. PMID- 8195726 TI - Heparin therapy. PMID- 8195727 TI - Acyclovir therapy. PMID- 8195728 TI - GDM screening. PMID- 8195729 TI - Health care ethics. PMID- 8195730 TI - Should we screen for hypothyroidism in the elderly? PMID- 8195731 TI - Thyroid disease in the elderly. Part 1. Prevalence of undiagnosed hypothyroidism. AB - BACKGROUND: The purpose of this study was to examine the prevalence of previously unrecognized hypothyroidism in elderly patients. METHODS: The study was conducted in a primary care geriatrics clinic. Three hundred seventy elderly patients (287 women, 83 men) between 60 and 97 years of age were included in the study. Medical records of patients were reviewed retrospectively. Serum thyroid-stimulating hormone (TSH), free thyroxine (T4), height, weight, demographic variables, clinical signs and symptoms of hypothyroidism, history of thyroid diseases and treatment with thyroid medications, comorbidities, and current medications were obtained from the medical records. Patients who had both elevated TSH levels (5.0 to 14.9 microU/mL) and normal free T4 levels (0.7 to 2.0 ng/dL) met the criteria for "subclinical hypothyroidism." The criteria for "overt hypothyroidism" were TSH levels > or = 15 microU/mL and low free T4 levels (< 0.7 ng/dL). RESULTS: At the initial visit to the clinic, 18.1% of the patients (62 female and 5 male) had an established history of past or current thyroid disease. Another 20 women (5.4%) had a history of thyroid surgery. Of the remaining 283 patients with no history of thyroid disease, 14.6% of the women and 15.4% of the men had subclinical hypothyroidism. Overt hypothyroidism was discovered and subsequently treated in two female patients and one male patient (1.0% and 1.3%, respectively). Thyroid status was not significantly related to age group (60 to 64 years; 65 to 74; 75 to 84; 85 and older). Comorbidities typically associated with hypothyroidism were no more prevalent in hypothyroid patients than in euthyroid patients. CONCLUSIONS: We found a high prevalence of newly diagnosed subclinical hypothyroidism in both elderly male and female patients. Thyroid status was not related to age or to coexisting diseases. The clinical significance of treating subclinical hypothyroidism merits investigation. PMID- 8195732 TI - Thyroid disease in the elderly. Part 2. Predictability of subclinical hypothyroidism. AB - BACKGROUND: The purpose of this study was to determine how well hypothyroidism could be predicted from clinical signs and symptoms in elderly patients with no known history of thyroid disease. METHODS: This retrospective study was conducted in a primary care geriatrics clinic. Two hundred eighty-three patients (205 women, 78 men), who were between the ages of 60 and 97 years of age and had no history of thyroid disease, were included in the study. Medical records of patients were reviewed for data obtained at their first visit to the clinic: serum thyroid-stimulating hormone (TSH), free thyroxine (T4), height, weight, demographic variables, clinical signs and symptoms of hypothyroidism, previous history of thyroid disease and treatment with thyroid medications, and current medications. RESULTS: Of the 283 patients with no previous history of thyroid disease, 15.4% of men and 14.6% of women had subclinical hypothyroidism (TSH levels of 5.0 to 14.9 microU/mL, and normal free T4 levels [0.7 to 2.0 ng/dL]). Overt hypothyroidism (TSH > or = 15.0 microU/mL, low free T4 < 0.7 ng/dL) was discovered and subsequently treated in one male and two female patients. There were no significant differences (P > .05) in the frequencies of any of the clinical signs and symptoms of hypothyroidism between euthyroid and hypothyroid patients. There was no significant relationship between TSH levels and the total number of hypothyroid symptoms experienced by all patients (r = -.004, P = .99). Logistic regression analyses determined that clinical signs and symptoms were poor predictors of subclinical hypothyroidism in these elderly patients. CONCLUSIONS: Thyroid status could not be predicted from clinical signs and symptoms in this sample of elderly community-dwelling patients. This finding substantiates the difficulty of diagnosing subclinical hypothyroidism in the elderly based solely on clinical features. PMID- 8195733 TI - Asthma and chlamydial infection: a case series. AB - BACKGROUND: Adult-onset asthma is frequently associated with antecedent respiratory symptoms that could represent either previously undiagnosed asthma or previous lung infections that result in subsequent asthma. To further investigate a reported association of Chlamydia pneumoniae infection and adult reactive airway disease, we looked for evidence of atypical infections in patients with acute wheezing and nonwheezing respiratory illnesses. METHODS: Pharyngeal cultures and acute and convalescent serology for C pneumoniae and Mycoplasma pneumoniae were obtained from 131 primary care outpatients (mean age, 36 years) with acute wheezing or nonwheezing respiratory illnesses. Peak flow measurements were obtained in patients with cough or wheeze. Spirometry before and after bronchodilator use was obtained to substantiate the diagnosis of chronic asthma in patients who had persistent wheezing and dyspnea after enrollment. RESULTS: Twelve (9.2%) of 131 patients were classified as having chronic asthma, 5/12 developed chronic asthma for the first time during the study period. Thirty (22.9%) patients were classified with acute asthmatic bronchitis, and 89 (67.9%) had nonwheezing illness. Two of the newly diagnosed asthmatics met serologic criteria for acute C pneumoniae infection, and one had serologic evidence for acute M pneumoniae infection. Compared with patients with nonwheezing respiratory illnesses, C pneumoniae seroreactivity was significantly (P < .001) associated with both chronic asthma and with acute asthmatic bronchitis. CONCLUSIONS: Acute wheezing illness was encountered frequently in this primary care setting. Although most acute wheezing respiratory illness resolved without obvious chronic sequelae, some patients had persistent symptoms and were diagnosed with chronic asthma. C pneumoniae seroreactivity was associated with both acute and chronic wheezing, suggesting that pulmonary infection with this intracellular pathogen plays a role in the natural history of reactive airway disease. PMID- 8195734 TI - Women's satisfaction with Norplant as compared with oral contraceptives. AB - BACKGROUND: Women's satisfaction with their chosen method of contraception has seldom been evaluated, especially in the primary care setting. This study compared women who use Norplant with those who use oral contraceptives with regard to patient satisfaction with, and the perceived advantages and disadvantages of, their birth control method. METHODS: We sent questionnaires to 115 Norplant users and 148 oral contraceptive users. The questionnaire asked for demographic data; a rating of level of satisfaction with their contraceptive; whether they would choose their method again; whether they would recommend their contraceptive to a friend; and what they perceived as its advantages and disadvantages. RESULTS: Sixty percent of responding Norplant users were satisfied with their method as compared with 72% of oral contraceptive users (P > .05). Sixty-three percent of Norplant users indicated that they would use their method again, compared with 88% of oral contraceptive users (P < .05). Seventy-four percent of Norplant users said they would recommend their method to a friend as compared with 97% of oral contraceptive users (P < .05). Oral contraceptive users reported significantly less menstrual bleeding and cramping than did Norplant users (P < .05), and Norplant users reported significantly more acne and bleeding irregularities (P < .05). CONCLUSIONS: In our study, the majority of responding Norplant and oral contraceptive users were satisfied with their current method of contraception. However, Norplant users reported being less willing to use their method again or to recommend it to a friend, as compared with women using oral contraceptives. Norplant users noted more bleeding irregularities, more cramping, and increased acne. PMID- 8195735 TI - Comparison of two topical preparations for the treatment of onychomycosis: Melaleuca alternifolia (tea tree) oil and clotrimazole. AB - BACKGROUND: The prevalence of onychomycosis, the most frequent cause of nail disease, ranges from 2% to 13%. Standard treatments include debridement, topical medications, and systemic therapies. This study assesses the efficacy and tolerability of topical application of 1% clotrimazole solution compared with that of 100% Melaleuca alternifolia (tea tree) oil for the treatment of toenail onychomycosis. METHODS: A double-blind, multicenter, randomized controlled trial was performed at two primary care health and residency training centers and one private podiatrist's office. The participants included 117 patients with distal subungual onychomycosis proven by culture. Patients received twice-daily application of either 1% clotrimazole (CL) solution or 100% tea tree (TT) oil for 6 months. Debridement and clinical assessment were performed at 0, 1, 3, and 6 months. Cultures were obtained at 0 and 6 months. Each patient's subjective assessment was also obtained 3 months after the conclusion of therapy. RESULTS: The baseline characteristics of the treatment groups did not differ significantly. After 6 months of therapy, the two treatment groups were comparable based on culture cure (CL = 11%, TT = 18%) and clinical assessment documenting partial or full resolution (CL = 61%, TT = 60%). Three months later, about one half of each group reported continued improvement or resolution (CL = 55%; TT = 56%). CONCLUSIONS: All current therapies have high recurrence rates. Oral therapy has the added disadvantages of high cost and potentially serious adverse effects. Topical therapy, including the two preparations presented in this paper, provide improvement in nail appearance and symptomatology. The use of a topical preparation in conjunction with debridement is an appropriate initial treatment strategy. PMID- 8195736 TI - Patient perspectives on computer-based medical records. AB - BACKGROUND: Despite emerging interest in computer-based patient records (CPRs), less than 1% of medical records in the United States are stored electronically. Some physicians may be reluctant to implement CPR systems because of fear that the physician-patient relationship would be adversely affected. This study ascertained the attitudes of patients regarding the use of CPR systems. METHODS: This study was an in-depth interview survey of 16 patients concerning the CPR system used at the family medicine department at the Medical University of South Carolina. Interview topics included patient knowledge, perceived advantages and disadvantages, and the impact of the CPR system on their relationship with their physician. RESULTS: Most patients were informed about the nature of the CPR system and had positive attitudes toward it. Common perceptions were that CPR provides physicians with easy access to information, facilitates clinical encounters, and improves physician-patient relationship and the quality of care delivered. Although confidentiality was the major concern expressed about the CPR system, only one respondent indicated that this factor limited his interaction with his physician. CONCLUSIONS: This study demonstrated patient acceptance and support for the CPR system in use at the study site. These findings should encourage physicians to use CPRs. PMID- 8195737 TI - Antiphospholipid syndrome. AB - The antiphospholipid syndrome is an illness characterized by recurrent venous or arterial thrombosis, recurrent fetal loss, and thrombocytopenia. It is diagnosed by the presence of antiphospholipid antibodies, such as anticardiolipin antibody or lupus anticoagulant. Although the antiphospholipid syndrome affects a significant number of patients, these patients may be unrecognized because the syndrome has not been well reported in the primary care literature. PMID- 8195738 TI - Pregnancy and extracranial shunts: case report and review of the literature. AB - This case involves a 32-year-old pregnant patient with a preexisting ventriculoperitoneal shunt. At term, she had a vaginal delivery with vacuum assistance, an epidural, and prophylactic antibiotics. Although there are no controlled studies validating the best course of management in such cases, there seems to be agreement that vaginal delivery can be attempted in the absence of other obstetrical indications for operative delivery. Obstruction of the shunt and, less commonly, abdominal cysts related to the distal end of the shunt are the principal obstetrical complications associated with a cerebrospinal shunt. PMID- 8195739 TI - Frenetic pharmaceuticals. PMID- 8195740 TI - The legacy of migraine. PMID- 8195741 TI - Norplant vs oral contraceptives. PMID- 8195742 TI - Complications of IDDM. PMID- 8195743 TI - Peritrophic matrix of the black fly Simulium vittatum: formation, structure, and analysis of its protein components. AB - The peritrophic matrix (PM) (same as peritrophic membrane) is secreted by the midgut epithelium of insects and completely surrounds the ingested food. The PM is likely to influence disease transmission by hematophagous insects. As a prelude to a more detailed examination of PM function, we report on morphological and molecular studies of the PM type 1 (PM1) from Simulium vittatum. The blood meal induces major changes in epithelial cell morphology: cells become flattened, microvilli decrease dramatically in number, and organelles redistribute in the cytoplasma. The PM1 forms within minutes of the blood meal. After 6 h the PM1 has reached its maximum thickness (approximately 13 microns) and strength. Two dimensional gel electrophoresis reveals two major PM1-specific proteins of 66 and 61 kDa. Synthesis of these PM1 proteins is likely to be induced by the blood meal, since they are not detectable prior to blood feeding. The time course of accumulation and disappearance of the PM1 proteins closely correlates with the appearance and disappearance of the PM1 itself. PMID- 8195744 TI - Morphodynamic hair bundles arising from sensory cell/supporting cell complexes frequency-tune nematocyst discharge in sea anemones. AB - Discharge of nematocysts from cnidocytes occurs in response to appropriate chemical and mechanical stimulation. In sea anemone tentacles, activating chemoreceptors for N-acetylated sugars shifts maximal discharge into vibrating targets to low frequencies corresponding to prey movements and induces hair bundles to elongate by approximately 1-2 microns. Until now, only indirect, correlative evidence linked these two events. Using cytochalasin D, we provide evidence that bundle elongation is necessary for the frequency shift. Moreover, we find that only bundles associated with sensory cell/supporting cell complexes elongate with chemosensitization, and not bundles associated with cnidocyte/supporting cell complexes as was previously thought. Cytochemical labeling of sensory cells, purported to be bipolar neurons connected to the nerve net, suggests that sensory cells may interconnect with each other and with cnidocytes. Taken together, these findings are incompatible with the classical view that cnidocytes are independent effectors of nematocyst discharge and, furthermore, implicate the involvement of morphodynamic neurons in fine-tuning vibration-dependent discharge of nematocysts into swimming prey. PMID- 8195745 TI - Acid-base status of a pulmonate land snail (Helix aspersa) and a prosobranch amphibious snail (Pomacea bridgesi) during dormancy. AB - Changes in metabolism and acid-base status were compared during dormancy in the pulmonate land snail Helix aspersa and a prosobranch amphibious snail Pomacea bridgesi. The typical condition of higher blood PCO2 and bicarbonate levels for air-breathing versus water-breathing vertebrates was shown for the two snail species. When exposed to dry air for 24 hr, both species depressed oxygen uptake by about 65%. In Pomacea, hypercapnia (increase in hemolymph PCO2 from 5.5 to 18 torr) resulting from dormancy produced no significant change in pH due to large increases in bicarbonate (over 17 mmol/l). In Helix, on the other hand, hypercapnia (increase in hemolymph PCO2 from 13 to 18 torr) resulting from dormancy produced a significant decrease in pH and a less than 7 mmol/l increase in bicarbonate. Pre-existing high levels of bicarbonate in Helix may prevent compensation of hypercapnia resulting from dormancy, similar to the case described for air-breathing vertebrates. Complete compensation of respiratory acidosis during the first 24 hr of dormancy in Pomacea suggests that metabolic rate suppression is independent of pH. PMID- 8195746 TI - Spinal cord neurite growth response to target tissue in a dose-dependent manner in vitro. AB - Neurite outgrowth from larval frog spinal cord explants in tissue culture previously has been shown to be enhanced and oriented in the presence of mesenchymal limb target tissue. Evidence that suggests the limb mesenchyme is the source of a motor neuron growth factor has prompted consideration of a possible target dose relationship in eliciting spinal neurite growth. Whereas typical experimental paradigms incorporate a single target explant in cocultures of neural and target tissues, we have challenged spinal cord explants with dual limb targets. Both the spinal cord explants and mesenchymal limb tissue segments were derived from young stage V Rana pipiens tadpoles. In comparison to cultures with a single limb, the spinal neurite density in the presence of two limbs increased more than twofold. Accompanying the increase in neuritic quantity was a substantial increase in the average length of the neurites. Over a two-week culture period there was little change in the relative differences between the single and double target cultures. Even though the double target tissues were placed adjacent to one another on one side of the cord explant, greatly enhanced neurite growth occurred on the contralateral side as well. The dramatic increase in neurite outgrowth in the presence of an additional target tissue provides further evidence that undifferentiated mesenchymal limb tissue is the source of a spinal neurite growth-promoting factor that may act in a dose-dependent manner with implications for both motor axon growth regulation and regeneration. PMID- 8195747 TI - A discussion of opiate concentrations in hair (Kintz, P. and Mangin, P., "Opiate concentrations in human head, axillary, and pubic hair," Journal of Forensic Sciences, Vol. 38, No. 3, May 1993, pp. 657-662.) PMID- 8195748 TI - A discussion of a suicide by self-decapitation. PMID- 8195749 TI - Forensic application of repetitive DNA markers to the species identification of animal tissues. AB - Highly repetitive DNA markers have been used for determining the species origin of animal tissues in cases of illegal commercialization and poaching of game animals. This approach has been used in cases involving white-tailed deer (Odocoileus virginianus), moose (Alces alces) and black bear (Ursus americanus). Digesting the DNA with various restriction enzymes, agarose electrophoresis and staining with ethidium bromide revealed unique banding patterns for each species. These patterns have been used to distinguish meat from game animal species from commercial sources of meat and organs. Data are presented from two Ontario court cases that demonstrate the application of the procedure. PMID- 8195750 TI - Identification of the heme compound copurified with deoxyribonucleic acid (DNA) from bloodstains, a major inhibitor of polymerase chain reaction (PCR) amplification. AB - The heme compound found in deoxyribonucleic acid (DNA) extracted from bloodstains, which is regarded as a major inhibitor of polymerase chain reaction (PCR), was characterized in comparison with alkaline and acid hematin, histidine and ammonia hemochromogens, and globin and serum albumin hemochromogens digested by proteinase K. Alkaline and acid hematin were almost completely removed by phenol/chloroform treatment and ethanol precipitation, so as not to be copurified with DNA from the specimens. Spectrophotometric results indicated that the contaminant was likely to be the product of proteinase K digestion of some heme blood protein complex, which was not completely extracted by organic solvents and remained in the ethanol precipitates of DNA. The results of polyacrylamide gradient gel electrophoresis and intensity of the inhibition of PCR suggested that the ligand of the contaminant was a somewhat large molecule, resistant to the proteolysis by proteinase K. The addition of bovine serum albumin to the reaction mixture prevented the inhibition of PCR by the heme compounds, probably by binding to the heme. This showed that the inhibition was not due to the irreversible inactivation of the enzyme. PMID- 8195751 TI - Radiographic identification of unknown human remains and interpreter experience level. AB - The use of radiographs as a means of identification of unknown remains is a well established method as performed by radiologists, forensic anthropologists, or pathologists. We devised a test to determine whether the degree of radiographic and medical knowledge of a film interpreter correlates with the degree of accuracy in making comparisons of radiographic unknowns. Three groups considered to be distinctly different in their level of medical knowledge and radiographic interpretive skills were chosen to evaluate forensic identification cases. Although all three groups identified a majority of cases correctly, none were completely accurate. The group with training in radiographic interpretation performed significantly better. Our study supports the need for trained interpreters in cases of forensic identification. PMID- 8195752 TI - De Clerambault syndrome (erotomania) in the criminal justice system: another look at this recurring problem. AB - While de Clerambault syndrome (erotomania) has long been a subject of scientific study, it has only recently become a frequent topic of media attention. A series of five individuals who were arrested for crimes related to their erotomanic delusion are presented. The psychiatric findings from this sample have potential social policy implication. PMID- 8195753 TI - Firearm suicides during confrontations with police. AB - We reviewed the case records of suicides in Marion County, Indiana (Indianapolis) and in surrounding counties from 1984 through 1992. Out of 1203 suicides, there were 14 in which armed, on-duty police officers were confronting, pursuing, or apprehending the subject of the death investigation. All subjects were male, and the peak age range was 30 to 34 years. The head, especially the right temple, was the usual site of the fatal wound. More than half of the incidents started as domestic disputes with a wife or girlfriend. Many of the others occurred when police officers pursued or arrested a suspect wanted for a previous felony. Ethanol was involved in less than half of the cases, and drugs were not a factor. In at least four cases, the presence of police was a factor that precipitated the suicide. The histories of the 14 cases demonstrate the potential for controversy and the challenges for forensic scientists investigating suicides during police confrontations. PMID- 8195754 TI - A DNA-based approach to the identification of insect species used for postmortem interval estimation. AB - Insect larvae found on a corpse can be used for estimating postmortem intervals. Here, we describe a molecular method for rapid identification of these insects. Specific insect DNA fragments were amplified using the polymerase chain reaction (PCR), followed by direct DNA sequencing of the amplification products. We sequenced 2300 base pairs of mitochondrial DNA from each of three blowfly species: Phormia regina, Phaenicia sericata and Lucilia illustris. All three species are important in forensic entomology. We found 118 nucleotide differences between the L. illustris and P. sericata sequences, 186 between L. illustris and P. regina, and 192 between P. sericata and P. regina. Based on these abundant DNA sequence differences, we can unambiguously identify the immature larval stages of these insects. These DNA sequence differences were also used to predict species specific, diagnostic restriction sites in the amplified DNA, and these predictions were verified by digestion with nine restriction enzymes. The DNA sequences reported here encode the mitochondrial COI, COII and tRNA-leucine genes. PMID- 8195755 TI - Handling and interpretation of crossbow injuries. AB - The longbow and crossbow are infrequently encountered by the forensic pathologist. As these weapons become more popular for sport and hunting, more fatalities may be anticipated. Three crossbow deaths (two homicides and one suicide) are presented. Included is the first report of a multiple shot death. The design and physics of the crossbow are described. The proper preservation of evidence, as well as wound analysis and interpretation, in such deaths are detailed. PMID- 8195756 TI - The reliability of skull/photograph superimposition in individual identification. AB - The accuracy of video superimposition methods for identifying unknown human skulls was examined. Three identified human skulls were each compared to 97 lateral view and 98 frontal view "mug shot" photographs using two television cameras, an electronic signal mixer, and a video monitor. The skulls were not from individuals represented by the photographs. All comparisons were done without using anterior dentition. The results found that 9.6% of the lateral view and 8.5% of the frontal view superimpositions were classified as a consistent fit based on the criteria that were identified. The incidence of false matches was reduced to 0.6% of the sample when a frontal view and lateral view photograph of the same individual were both compared to one skull. It was concluded that without anterior dentition, skull/photograph superimposition is reliable when two or more photographs, clearly depicting the facial features from different angles, are used in the comparison. PMID- 8195757 TI - Pedophiles' ratings of adult and child photographs using a semantic differential. AB - Recent knowledge of the widespread extent of child sexual abuse and its consequences has led to an increasing interest in the understanding and treatment of perpetrators. This study examined a group of pedophiles in an English Special Hospital to determine possible characteristics that make children attractive and adults unattractive to them, using Repertory Grid technique and Semantic Differential. A small number of significant findings suggest that pedophiles may perceive some children and women in an unusual way. The large number of insignificant findings are discussed with reference to the sensitivity of the instrument; the pedophiles' desire to give socially acceptable answers; and subject characteristics of low IQ and "psychopathic disorder." Future directions for research are suggested. PMID- 8195758 TI - Microanalysis of carbon monoxide in blood by head-space capillary gas chromatography. AB - A gas chromatographic procedure for the determination of carboxyhaemoglobin in blood was improved by using a capillary system in combination with a micro thermal conductivity detector. This system is very sensitive with high resolutions. The analytical time is reduced to approximately two minutes. Using sulphuric acid as the liberating agent of carbon monoxide, a gradual and reproducible release of carbon monoxide was seen. This shortens the time in emergency cases for sample preparation. PMID- 8195759 TI - Reanalysis of forensic urine specimens containing benzoylecgonine and THC-COOH. AB - Drug testing laboratories are often requested to retest specimens that have tested positive. The reproducibility of analytical retest data for delta-9 tetrahydrocannabinol-9-carboxylic acid (THC-COOH) and benzoylecgonine in specimens that had previously been analyzed and then frozen by the Navy Drug Screening Laboratory, Great Lakes is examined in this study. All specimens were tested by gas chromatography/mass spectrometry (GC/MS). Retest values generally showed a decrease in concentration but exhibited considerable variability. Eighty five THC-COOH positive urine specimens stored frozen for 1 to 10 months (average 2.3 months) declined an average of 25% (range, +30% to -80%) and 61 benzoylecgonine positive urine specimens stored for 1 to 8 months (average 2.3 months) declined an average of 19% (ranged +20% to -100%) from initial GC/MS test results. Drugs were found to partition into strata when frozen in urine because of the thermodynamics of the freezing process. To assure a homogenous solution for repeat testing, specimens that have been frozen and thawed were gently mixed before analysis. PMID- 8195760 TI - Postmortem clomipramine: therapeutic or toxic concentrations? AB - Postmortem blood and liver concentrations of clomipramine were determined in ten cases by high performance liquid chromatography (HPLC). Blood concentrations ranged from 0.21 to 4.9 mg/L, and liver concentrations from 7.0 to 320 mg/kg. Two cases associated with clomipramine toxicity were clearly differentiated from other cases by the analysis of liver. The concentrations of clomipramine in these two cases were 3.3 and 1.8 mg/L in blood, and 280 and 320 mg/kg in liver. The liver concentrations were 10 to 30 fold greater in the deaths associated with drug toxicity compared with the other cases. One case, where cardiac blood was collected in place of femoral blood, showed a high blood concentration (4.9 mg/L), but an arguably therapeutic liver concentration (13 mg/kg). The analysis of femoral blood together with liver provides the best guide as to the significance of post-mortem clomipramine concentrations. PMID- 8195761 TI - Pop-rock music as precipitating cause in youth suicide. AB - The plaintiffs in a law suit alleged that the heavy metal rock band Judas Priest, and its publisher CBS, were liable for damages to two youths who shot themselves after listening to the band's album. Crucial issues included "proximate cause" and "precipitating cause" in suicide, and the alleged role of subliminal messages. The judge ruled that although the "heavy metal" music might have had a toxic influence, the sounds and words are protected by the free speech first amendment. The influence of subliminal messages on behavior is unproven. There were many other elements in the personalities and situations of the victims to account for their self-destructive behavior. PMID- 8195762 TI - Genetic typing of the DQA1*4 alleles by restriction enzyme digestion of the PCR product obtained with the DQ Alpha Amplitype kit. AB - The three DQ Alpha 4 alleles, 4.1 (0501), 4.2 (0401), and 4.3 (0601) cannot be distinguished with the reverse dot blot DQ Alpha Amplitype Kit. A previous report (Yunis, I. et al., Tissue Antigens, Vol. 39, 1992, pp. 182-186) indicated that the typing of these three alleles can be accomplished by endonuclease digestion of the PCR product that is produced following amplification with the DQ Alpha primers with Fok I and Rsa I. We report here the use of this method to type the DQA1*0401, 0501 and 0601 alleles in the PCR product obtained with the DQ Alpha Amplitype Kit. We have analyzed the PCR product obtained in over 200 forensic samples. We have found that in all of these cases, it is possible to assign a type to those samples that type as DQ Alpha 4 with the Amplitype Kit. Furthermore, we have found the technique to be useful in some cases where it has not been previously possible to distinguish individuals or samples that have the DQ Alpha 4 allele and type identically with respect to all other DQ Alpha alleles. PMID- 8195763 TI - The use of minisatellite variant repeat-polymerase chain reaction (MVR-PCR) to determine the source of saliva on a used postage stamp. AB - In this paper we report the identification of an individual using the MVR-PCR technique on DNA extracted from single and multiple discs (3 mm) punched from a licked stamp attached to an envelope. The individual's code was successfully and uniquely matched to one already present within a database of 500 MVR codes which had been generated in a separate laboratory. The exercise illustrates the suitability of MVR-PCR for forensic samples and demonstrates the power of this rapid and novel identification system. PMID- 8195764 TI - Achalasia, the Valsalva maneuver, and sudden death: a case report. AB - A 48 year old woman with no significant prior medical history was found dead by her husband in their home. The autopsy disclosed no anatomic reason for her death; however, the length of the esophagus was found to be massively dilated, with stenosis of the cardiac sphincter, and contained swallowed food material. Her husband disclosed that she had experienced difficulty in swallowing for over 10 years, and had to "strain" to move food into the stomach, although she had never consulted a physician regarding the problem. No gross or microscopic anatomic cardiac abnormalities were identified. The death was ascribed to a cardiac arrhythmia arising from the Valsalva maneuver, which she used to move her ingested food across the stenotic gastroesophageal juncture. The Valsalva maneuver, which increases the intrathoracic pressure by forcing expiratory effort against a closed glottis, has been associated with cardiac arrhythmias and rarely, sudden death. Lethal cardiac arrhythmias should be considered when sudden deaths occur in individuals with esophageal motility disorders, as well as in other situations where the Valsalva maneuver may have been used, and where no other anatomic cause of death is identified. PMID- 8195765 TI - Delayed fatal hemothorax due to traumatic carotid dissection: a case report of a previously unreported cause of death. AB - A unique case of delayed fatal hemothorax in a 12-year-old girl resulting from atypical dissection of a traumatic carotid aneurysm is reported, due to occult neck trauma received in a sledding accident which occurred one week prior to death. Aspects of traumatic carotid dissection and forensic implications of delayed presentation of such findings in the setting of occult trauma are discussed. PMID- 8195766 TI - SEM analysis of incinerated teeth as an aid to positive identification. AB - Tooth crown and root fragments from a crime scene in which the remains were purposefully cremated, crushed and scattered were analyzed using a scanning electron microscope (SEM) in order to aid the identification process. The SEM was used to confirm the presence of parallel striations in tooth enamel and dentine as a means of determining past dental restoration. In the case presented, incinerated tooth fragments of determined type and position were subjected to SEM analysis, and ascertained to have had previous dental work that matched antemortem dental records of a missing person. PMID- 8195767 TI - Prenatal exclusion of paternity by PCR-FLP analysis of VNTR. AB - A prenatal paternity test was requested by a 30-year-old woman. Variable number of tandem repeat (VNTR) systems were used for DNA analysis by means of amplification and electrophoresis followed by ethidium bromide staining or Southern blotting and oligonucleotide hybridization. Exclusion of paternity could be established on the basis of the great polymorphism and heterozygosity indexes of these genetic systems. This rapid method presents several advantages in contrast with other recombinant DNA techniques such as HLA class II oligotyping or RFLP. PMID- 8195768 TI - Round and round it goes where it stops nobody knows. PMID- 8195769 TI - Health-care reform. Its burden on academic medical centers. PMID- 8195770 TI - Medical schools on the fault line. PMID- 8195771 TI - Yes, I am a doctor. PMID- 8195772 TI - BRFSS-based survey of the Florida public on restaurant smoking. AB - A total of 2,246 Floridians were randomly surveyed by telephone concerning the Florida Clean Indoor Air Act and smoking in restaurants. Only 28.8% responded correctly that restaurant smoking is prohibited unless a manager's sign specifically permits it. More than 80% of smokers felt free to light up in the absence of such signs and over 45% of nonsmokers did not recognize this as an infringement of their rights. Although about three-quarters of Floridians are nonsmokers, only about half the state's restaurant seating capacity was intended for nonsmokers by managers. Based on their own experience, smoking Floridians were much more likely (67.1%) to be satisfied with their allocation of seating than were nonsmokers (45.9%). Uniquely among states, Florida's law preempts all local ordinances, past and future. The Clean Indoor Air Act is of little practical value because it is understood by so few. It allows no restrictions on smoking in 42% of Florida's restaurants, those with fewer than 51 seats. PMID- 8195773 TI - Cardiac transplantation. University of Miami/Jackson Memorial hospital experience. AB - Cardiac transplantation at the University of Miami/Jackson Memorial Medical Center began in November 1986. Up to April 1993, 220 potential recipients were evaluated and 84 accepted. Sixty-three patients received transplants while 14 died awaiting a donor heart. Within six years, the average recipient age has increased from 40 to 59 years. The overall one, two, and five-year survival rates (including operative deaths) are 89.5%, 82%, and 76%, respectively. Postoperative complications and mortality were related to infection or rejection frequently encountered within the first 28 months; thereafter the actuarial survival curve showed minimal decay and the complication rate declined. One or more hospital readmissions were needed in 38 of 57 (67%) survivors. Among the 50 long-term survivors, 42% are working and 84% are in New York Heart Association functional Class I. PMID- 8195775 TI - Florida's grand experiment addresses practice parameters. PMID- 8195774 TI - Florida's tuberculosis epidemic. Public health response. AB - Florida ranked fourth in the nation with 1,707 tuberculosis cases reported in 1992 for a rate of 12.7 per 100,000 population. Thirteen percent of these patients had AIDS. Recent cases in prisons, shelters, hospitals and schools have stimulated interest and media coverage. Resurgence of strains of multiple-drug resistant tuberculosis is a serious concern. The Florida Department of Health and Rehabilitative Services, in collaboration with allied agencies, has utilized several initiatives in response. The most significant, Tuberculosis Epidemic Containment Plan, details intervention strategies needed to eliminate TB in the state by the year 2010. Successful implementation depends upon local TB prevention and control coalitions that include private and public sector providers. PMID- 8195776 TI - Physician-controlled PHOs should learn from their competitors. PMID- 8195777 TI - Cartilage aggrecan. Biosynthesis, degradation and osteoarthritis. AB - The main "shock absorbing" molecule in cartilage is the proteoglycan, aggrecan, which is trapped within a meshwork of collagen fibrils. Articular cartilage damage in osteoarthritis is associated with damage to the aggrecan protein moiety. This results in abnormal loss of aggrecan which in turn increases the propensity of the joint surface to be damaged. Presently, the treatment for arthritis, pain-relieving drugs, affects the symptoms. End-stage osteoarthritis requires joint replacement surgery. To a certain extent, both the degradation and the repair of cartilage can be understood at the level of the biochemistry of cartilage matrix and the biology of the chondrocyte. PMID- 8195778 TI - Physician advertising in Florida. PMID- 8195779 TI - Signaling between intracellular Ca2+ stores and depletion-activated Ca2+ channels generates [Ca2+]i oscillations in T lymphocytes. AB - Stimulation through the antigen receptor (TCR) of T lymphocytes triggers cytosolic calcium ([Ca2+]i) oscillations that are critically dependent on Ca2+ entry across the plasma membrane. We have investigated the roles of Ca2+ influx and depletion of intracellular Ca2+ stores in the oscillation mechanism, using single-cell Ca2+ imaging techniques and agents that deplete the stores. Thapsigargin (TG; 5-25 nM), cyclopiazonic acid (CPA; 5-20 microM), and tert butylhydroquinone (tBHQ; 80-200 microM), inhibitors of endoplasmic reticulum Ca(2+)-ATPases, as well as the Ca2+ ionophore ionomycin (5-40 nM), elicit [Ca2+]i oscillations in human T cells. The oscillation frequency is approximately 5 mHz (for ATPase inhibitors) to approximately 10 mHz (for ionomycin) at 22-24 degrees C. The [Ca2+]i oscillations resemble those evoked by TCR ligation in terms of their shape, amplitude, and an absolute dependence on Ca2+ influx. Ca(2+)-ATPase inhibitors and ionomycin induce oscillations only within a narrow range of drug concentrations that are expected to cause partial depletion of intracellular stores. Ca(2+)-induced Ca2+ release does not appear to be significantly involved, as rapid removal of extracellular Ca2+ elicits the same rate of [Ca2+]i decline during the rising and falling phases of the oscillation cycle. Both transmembrane Ca2+ influx and the content of ionomycin-releasable Ca2+ pools fluctuate in oscillating cells. From these data, we propose a model in which [Ca2+]i oscillations in T cells result from the interaction between intracellular Ca2+ stores and depletion-activated Ca2+ channels in the plasma membrane. PMID- 8195780 TI - Spontaneous activation of light-sensitive channels in Drosophila photoreceptors. AB - In Drosophila photoreceptors light induces phosphoinositide hydrolysis and activation of Ca(2+)-permeable plasma membrane channels, one class of which is believed to be encoded by the trp gene. We have investigated the properties of the light-sensitive channels under conditions where they are activated independently of the transduction cascade. Whole-cell voltage clamp recordings were made from photoreceptors in a preparation of dissociated Drosophila ommatidia. Within a few minutes of establishing the whole-cell configuration, there is a massive spontaneous activation of cation-permeable channels. When clamped near resting potential, this "rundown current" (RDC) accelerates over several seconds, peaks, and then relaxes to a steady-state which lasts indefinitely (many minutes). The RDC is invariably associated with a reduction in sensitivity to light by at least 100-fold. The RDC has a similar absolute magnitude, reversal potential, and voltage dependence to the light-induced current, suggesting that it is mediated by the same channels. The RDC is almost completely (> or = 98%) blocked by La3+ (10-20 microM) and is absent, or reduced and altered in the trp mutant (which lacks a La(3+)-sensitive light-dependent Ca2+ channel), suggesting that it is largely mediated by the trp-dependent channels. Power spectra of the steady-state noise in the RDC can be fitted by simple Lorentzian functions consistent with random channel openings. The variance/mean ratio of the RDC noise suggests the underlying events (channels) have conductances of approximately 1.5-4.5 pS in wild-type (WT), but 12-30 pS in trp photoreceptors. Nevertheless, the power spectra of RDC noise in WT and trp are indistinguishable, in both cases being fitted by the sum of two Lorentzians with a major time constant (effective "mean channel open time") of 1-2 ms and a minor component at higher frequencies (approximately 0.2 ms). This implies that the noise in the WT RDC may actually be dominated by non-trp-dependent channels and that the trp-dependent channels may be of even lower unit conductance. PMID- 8195781 TI - Calcium-dependent inactivation of light-sensitive channels in Drosophila photoreceptors. AB - Whole-cell voltage clamp recordings were made from photoreceptors of dissociated Drosophila ommatidia under conditions when the light-sensitive channels activate spontaneously, generating a "rundown current" (RDC). The Ca2+ and voltage dependence of the RDC was investigated by applying voltage steps (+80 to -100 mV) at a variety of extracellular Ca2+ concentrations (0-10 mM). In Ca(2+)-free Ringer large currents are maintained tonically throughout 50-ms-long voltage steps. In the presence of external Ca2+, hyperpolarizing steps elicit transient currents which inactivate increasingly rapidly as Ca2+ is raised. On depolarization inactivation is removed with a time constant of approximately 10 ms at +80 mV. The Ca(2+)-dependent inactivation is suppressed by 10 mM internal BAPTA, suggesting it requires Ca2+ influx. The inactivation is absent in the trp mutant, which lacks one class of Ca(2+)-selective, light-sensitive channel, but appears unaffected by the inaC mutant which lacks an eye-specific protein kinase C. Hyperpolarizing voltage steps applied during light responses in wild-type (WT) flies before rundown induce a rapid transient facilitation followed by slower inhibition. Both processes accelerate as Ca2+ is raised, but the time constant of inhibition (12 ms with 1.5 mM external Ca2+ at -60 mV) is approximately 10 times slower than that of the RDC inactivation. The Ca(2+)-mediated inhibition of the light response recovers in approximately 50-100 ms on depolarization, recovery being accelerated with higher external Ca2+. The Ca2+ and voltage dependence of the light-induced current is virtually eliminated in the trp mutant. In inaC, hyperpolarizing voltage steps induced transient currents which appeared similar to those in WT during early phases of the light response. However, 200 ms after the onset of light, the currents induced by voltage steps inactivated more rapidly with time constants similar to those of the RDC. It is suggested that the Ca(2+)-dependent inactivation of the light-sensitive channels first occurs at some concentration of Ca2+ not normally reached during the moderate illumination regimes used, but that the defect in inaC allows this level to be reached. PMID- 8195782 TI - Voltage- and time-dependent K+ channel currents in the basolateral membrane of villus enterocytes isolated from guinea pig small intestine. AB - Patch-clamp studies were carried out in villus enterocytes isolated from the guinea pig proximal small intestine. In the whole-cell mode, outward K+ currents were found to be activated by depolarizing command pulses to -45 mV. The activation followed fourth order kinetics. The time constant of K+ current activation was voltage-dependent, decreasing from approximately 3 ms at -10 mV to 1 ms at +50 mV. The K+ current inactivated during maintained depolarizations by a voltage-independent, monoexponential process with a time constant of approximately 470 ms. If the interpulse interval was shorter than 30 s, cumulative inactivation was observed upon repeated stimulations. The steady state inactivation was voltage-dependent over the voltage range from -70 to -30 mV with a half inactivation voltage of -46 mV. The steady state activation was also voltage-dependent with a half-activation voltage of -22 mV. The K+ current profiles were not affected by chelation of cytosolic Ca2+. The K+ current induced by a depolarizing pulse was suppressed by extracellular application of TEA+, Ba2+, 4-aminopyridine or quinine with half-maximal inhibitory concentrations of 8.9 mM, 4.6 mM, 86 microM and 26 microM, respectively. The inactivation time course was accelerated by quinine but decelerated by TEA+, when applied to the extracellular (but not the intracellular) solution. Extracellular (but not intracellular) applications of verapamil and nifedipine also quickened the inactivation time course with 50% effective concentrations of 3 and 17 microM, respectively. Quinine, verapamil and nifedipine shifted the steady state inactivation curve towards more negative potentials. Outward single K+ channel events with a unitary conductance of approximately 8.4 pS were observed in excised inside-out patches of the basolateral membrane, when the patch was depolarized to -40 mV. The ensemble current rapidly activated and thereafter slowly inactivated with similar time constants to those of whole-cell K+ currents. It is concluded that the basolateral membrane of guinea pig villus enterocytes has a voltage-gated, time-dependent, Ca(2+)-insensitive, small conductance K+ channel. Quinine, verapamil, and nifedipine accelerate the inactivation time course by affecting the inactivation gate from the external side of the cell membrane. PMID- 8195784 TI - Circadian regulation of teleost retinal cone movements in vitro. AB - In the retinas of many species of lower vertebrates, retinal photoreceptors and pigment epithelium pigment granules undergo daily movements in response to both diurnal, and in the case of teleost cone photoreceptors, endogenous circadian signals. Typically, these cone movements take place at dawn and at dusk when teleosts are maintained on a cyclic light (LD) regime, and at expected dawn and expected dusk when animals are maintained in continuous darkness (DD). Because these movements are so strictly controlled, they provide an overt indicator of the stage of the underlying clock mechanism. In this study we report that both light-induced and circadian-driven cone myoid movements in the Midas cichlid (Cichlasoma citrinellum), occur normally in vitro. Many of the features of retinomotor movements found in vivo also occur in our culture conditions, including responses to light and circadian stimuli and dopamine. Circadian induced predawn contraction and maintenance of expected day position in response to circadian modulation, are also normal. Our studies suggest that circadian regulation of cone myoid movement in vitro is mediated locally by dopamine, acting via a D2 receptor. Cone myoid contraction can be induced at midnight and expected mid-day by dark culture with dopamine or the D2 receptor agonist LY171555. Further, circadian induced predawn contraction can be increased with either dopamine or LY171555, or may be reversed with the dopamine D2 antagonist, sulpiride. Sulpiride will also induce cone myoid elongation in retinal cultures at expected mid-day, but will not induce cone myoid elongation at dusk. In contrast, circadian cone myoid movements in vitro were unaffected by the D1 receptor agonist SCH23390, or the D1 receptor antagonist SKF38393. Our short-term culture experiments indicate that circadian regulation of immediate cone myoid movement does not require humoral control but is regulated locally within the retina. The inclusion of dopamine, or dopamine receptor agonists and antagonists in our cultures, has indicated that retinal circadian regulation may be mediated by endogenously produced dopamine, which acts via a D2 mechanism. PMID- 8195783 TI - Structural requirements for charged lipid molecules to directly increase or suppress K+ channel activity in smooth muscle cells. Effects of fatty acids, lysophosphatidate, acyl coenzyme A and sphingosine. AB - We determined the structural features necessary for fatty acids to exert their action on K+ channels of gastric smooth muscle cells. Examination of the effects of a variety of synthetic and naturally occurring lipid compounds on K+ channel activity in cell-attached and excised membrane patches revealed that negatively charged analogs of medium to long chain fatty acids (but not short chain analogs) as well as certain other negatively charged lipids activate the channels. In contrast, positively charged, medium to long chain analogs suppress activity, and neutral analogs are without effect. The key requirements for effective compounds seem to be a sufficiently hydrophobic domain and the presence of a charged group. Furthermore, those negatively charged compounds unable to "flip" across the bilayer are effective only when applied at the cytosolic surface of the membrane, suggesting that the site of fatty acid action is also located there. Finally, because some of the effective compounds, for example, the fatty acids themselves, lysophosphatidate, acyl Coenzyme A, and sphingosine, are naturally occurring substances and can be liberated by agonist-activated or metabolic enzymes, they may act as second messengers targeting ion channels. PMID- 8195786 TI - Special issue: Calcium and neuronal plasticity. PMID- 8195785 TI - Binding of benzocaine in batrachotoxin-modified Na+ channels. State-dependent interactions. AB - Hille (1977. Journal of General Physiology. 69:497-515) first proposed a modulated receptor hypothesis (MRH) to explain the action of benzocaine in voltage-gated Na+ channels. Using the MRH as a framework, we examined benzocaine binding in batrachotoxin (BTX)-modified Na+ channels under voltage-clamp conditions using either step or ramp command signals. We found that benzocaine binding is strongly voltage dependent. At -70 mV, the concentration of benzocaine that inhibits 50% of BTX-modified Na+ currents in GH3 cells (IC50) is 0.2 mM, whereas at +50 mV, the IC50 is 1.3 mM. Dose-response curves indicate that only one molecule of benzocaine is required to bind with one BTX-modified Na+ channel at -70 mV, whereas approximately two molecules are needed at +50 mV. Upon treatment with the inactivation modifier chloramine-T, the binding affinity of benzocaine is reduced significantly at -70 mV, probably as a result of the removal of the inactivated state of BTX-modified Na+ channels. The same treatment, however, enhances the binding affinity of cocaine near this voltage. External Na+ ions appear to have little effect on benzocaine binding, although they do affect cocaine binding. We conclude that two mechanisms underlie the action of local anesthetics in BTX-modified Na+ channels. Unlike open-channel blockers such as cocaine and bupivacaine, neutral benzocaine binds preferentially with BTX-modified Na+ channels in a closed state. Furthermore, benzocaine can be modified chemically so that it behaves like an open-channel blocker. This compound also elicits a use-dependent block in unmodified Na+ channels after repetitive depolarizations, whereas benzocaine does not. The implications of these findings for the MRH theory will be discussed. PMID- 8195787 TI - Confocal laser scanning microscopy reveals voltage-gated calcium signals within hippocampal dendritic spines. AB - The induction of long-term potentiation (LTP) is generally assumed to be triggered by Ca2+ entry into dendritic spines via NMDA receptor-gated channels. A previous computational model proposed that spines serve several functions in this process. First, they compartmentalize and amplify increase in [Ca2+]i. Second, they augment the nonlinear relationship between synaptic strength and the probability or magnitude of LTP induction. Third, they isolate the metabolic machinery responsible for LTP induction from increases in [Ca2+]i produced by voltage-gated Ca2+ channels in the dendritic shaft. Here we examine this last prediction of the model using methods that combine confocal microscopy with simultaneous neurophysiological recordings in hippocampal brain slices. Either of two Ca(2+)-sensitive dyes were injected into CA1 pyramidal neurons. Direct depolarization of the neurons via the somatic electrode produced clear increases in Ca2+ signals within the dendritic spines, a result that was not predicted by the previous spine model. Our new spine model suggests that some of this signal could theoretically result from Ca(2+)-bound dye diffusing from the dendritic shaft into the spine. Dye diffusion alone cannot, however, explain the numerous cases in which the Ca2+ signal in the spine was considerably larger than that in the adjacent dendritic shaft. The latter observations raise the possibility of voltage-gated Ca2+ entry directly into the spine or else perhaps via Ca(2+) dependent Ca2+ release. The new spine model accommodates these observations as well as several other recent experimental results. PMID- 8195788 TI - Calcium signaling in dendritic spines of hippocampal neurons. AB - Intracellular Ca2+ dynamics have been measured using imaging techniques in dendrites and spines of CA3 hippocampal neurons in brain slice under both acute and tissue culture conditions. In response to presynaptic stimulation, micromolar levels of Ca2+ are rapidly reached in spines of distal dendrites. If stimulus parameters are chosen judiciously so as to minimize postsynaptic firing, then the dendrite shaft increases are far less. Spine Ca2+ increases are largely dependent upon activation of NMDA receptors. At the large mossy fiber synapses, presynaptic stimuli also produce large Ca2+ increases but the differences in shaft-spine Ca2+ levels are much less; often they are insignificant. Also at these locations, postsynaptic firing, without presynaptic stimulation is sufficient to produce large increases in spine Ca2+ levels. PMID- 8195790 TI - Nonlinear propagation of agonist-induced cytoplasmic calcium waves in single astrocytes. AB - In astrocytes in primary culture, activation of neurotransmitter receptors results in intracellular calcium signals that propagate as waves across the cell. Similar agonist-induced calcium waves have been observed in astrocytes in organotypic cultures in response to synaptic activation. By using primary cultured astrocytes grown on glass coverslips, in conjunction with fluorescence microscopy we have analyzed agonist-induced Ca2+ wave initiation and propagation in individual cells. Both norepinephrine and glutamate elicited Ca2+ signals which were initiated focally and discretely in one region of the cell, from where the signals spread as waves along the entire length of the cell. Analysis of the wave propagation and the waveform revealed that the propagation was nonlinear with one or more focal loci in the cytoplasm where the wave was regeneratively amplified. These individual loci appear as discrete focal areas 7-15 microns in diameter and having intrinsic oscillatory properties that differ from each other. The wave initiation locus and the different amplification loci remained invariant in space during the course of the experiment and supported an identical spatiotemporal pattern of signalling in any given cell in response to multiple agonist applications and when stimulated with different agonists which are coupled via InsP3. Cytoplasmic Ca2+ concentration at rest was consistently higher (17 +/- 4 nM, mean +/- S.E.M.) in the wave initiation locus compared with the rest of the cytoplasm. The nonlinear propagation results from significant changes in signal rise times, amplitudes, and wave velocity in cellular regions of active loci. Analysis of serial slices across the cell revealed that the rise times and amplitudes of local signals were as much as three- to fourfold higher in the loci of amplification. A phenomenon of hierarchy in local amplitudes of the signal in the amplification loci was observed with the wave initiation locus having the smallest and the most distal locus having the largest amplitude. By this mechanism locally very high concentrations of Ca2+ are achieved in strategic locations in the cell in response to receptor activation. While the average wave velocity calculated over the length of the cell was 10-15 microns/s, in the active loci rates as high as 40 microns/s were measured. Wave velocity was fivefold lower in regions of the cell separating active loci. The differences in the intrinsic oscillatory periods give rise to local Ca2+ waves that show the properties of collision and annihilation. It is hypothesized that the wave front provokes regenerative Ca2+ release from specialized areas in the cell where the endoplasmic reticulum is endowed with higher density of InsP3 receptor channels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8195789 TI - Intracellular calcium mobilization and neurite outgrowth in mammalian neurons. AB - Cultured adult rat dorsal root ganglion (DRG) neurons were used to study depolarization-induced Ca2+ mobilization and the effects of intracellular Ca2+ depletion on neurite outgrowth. Cytoplasmic and nuclear Ca2+ signals were visualized in dissociated DRG neurons using confocal scanning laser microscopy and the Ca2+ indicator dye fluo-3. The depolarization-induced Ca2+ signals were highest in neurons during the first few days in culture, prior to neurite extension; during this time nuclear signals exceeded those of the cytoplasm severalfold. After several days in culture, neurons began to arborize, depolarization-induced Ca2+ signals became attenuated, and nuclear signals no longer exceeded those of the cytoplasm. Elevated Ca2+ signals were dependent upon both Ca2+ influx and intact intracellular Ca2+ stores, indicating that the signals are generated by calcium-induced calcium release (CICR). Thapsigargin, an endoplasmic reticulum Ca2+ ATPase inhibitor, depleted intracellular Ca2+ stores and blocked the induction of the large nuclear Ca2+ signals. Treating DRG neurons briefly with thapsigargin (200 nM for 20 min) shortly after plating reduced subsequent neuritogenesis, implying that intact Ca2+ stores are necessary for initiating neurite outgrowth. Immunostaining of DRG neurons with antibodies to Ca2+/calmodulin-dependent kinase II (CaM kinase II) demonstrated that this enzyme is present in the nucleus at early times in culture. These observations are consistent with the idea that CICR triggered by Ca2+ entry subsequent to depolarization may elicit neurite outgrowth by activating nuclear enzymes appropriate for such outgrowth. PMID- 8195791 TI - Resonant activation of calcium signal transduction in neurons. AB - The relevant parameters of calcium fluxes mediating activation of immediate-early genes and the collapse of growth cones in mouse DRG neurons in response to action potentials delivered in different temporal patterns were measured in a multicompartment cell culture preparation using digital fluorescence videomicroscopy. Growth cone collapse was produced by trains of action potentials causing a large rise in [Ca2+]i, but after chronic exposure to patterned stimulation growth cones regenerated and became insensitive to the stimulus induced increase in [Ca2+]i. Calcium reached similar peak concentrations, but the [Ca2+]i increased more slowly than in naive growth cones (time constant of 6.0 s versus 1.4 s in naive growth cones). Semiquantitative PCR measurements of gene expression showed that pulsed stimulation delivered at 1-min intervals for 30 min induced expression of c-fos, but the same total number of action potentials delivered at 2-min intervals failed to induce c-fos expression, even though this stimulus induces a larger peak [Ca2+]i than the effective stimulus pattern. The experiments suggest that the kinetics of calcium fluxes produced by different patterns of stimulation, and changes in the kinetics of calcium flux in neurons under different states of activation, are critical in determining the effects of action potentials on growth cone motility or expression of IE genes during development of neuronal circuits. We propose that differences in kinetics of individual reactions in the stimulus-response pathway may lead to resonance of activation in the neuron, such that certain processes will be selectively activated by particular temporal patterns of stimulation. PMID- 8195792 TI - The plasma membrane calcium pump: functional domains, regulation of the activity, and tissue specificity of isoform expression. AB - The plasma membrane Ca2+ pump is responsible for the fine regulation of the intracellular Ca2+ level and is thus involved in the control of several cellular processes. The activity of the pump is regulated by a multiplicity of mechanisms, among which are calmodulin, acidic phospholipids, kinase-mediated phosphorylation, or an oligomerization process. The C-terminal part of the molecule interacts with the region of the pump close to the active site, leading to the decrease of the activity in the resting state. Four genes coding for different isoforms of the plasma membrane Ca2+ ATPase are known in humans. Isoform 1 and 4 represent housekeeping isoforms, whereas isoforms 2 and 3 are only present in specialized tissues. The variability of the protein is further increased by alternative RNA splicing at two sites (A, C). Alternative splicing occurs within (splice site C) or near (splice site A) regions coding for regulatory domains of the protein. In all isoforms a corresponding splice form exists at both splice sites. These common splice forms are present in all tissues, whereas isoform unique splice forms are normally only present in specialized tissues. In neuronal tissues all isoforms and almost the complete set of splice forms are found. The transcripts of the different isoforms are distributed in a region-specific manner in neuronal tissues. PMID- 8195793 TI - Proteolytic activity, synapse elimination, and the Hebb synapse. AB - The Hebb synapse has been postulated to serve as a mechanism subserving both regulation of synaptic strength in the adult nervous system (long-term potentiation and depression) and developmental activity-dependent plasticity. According to this model, pre- and postsynaptic temporal concordance of activity results in strengthening of connections, while discordant activity results in synapse weakening. Evidence is presented that proteases and protease inhibitors may be involved in modification of synaptic strength. This leads to a modification of the Hebb assumptions, namely that postsynaptic activity results in protease elaboration with a consequent general reduction of synaptic connections to the active postsynaptic element. Further, presynaptic activity, if strong enough, induces local release of a protease inhibitor, such as protease nexin I, which neutralizes proteolytic activity and produces a relative preservation of the active input. This formulation produces many of the effects of the classical Hebbian construction, but the protease/inhibitor model suggests additional specific mechanistic features for activity-dependent plasticity. PMID- 8195794 TI - Calcium-dependent postsynaptic exocytosis: a possible mechanism for activity dependent synaptic modulation. AB - Elevation of cytosolic Ca2+ level in the postsynaptic cell is critical for the induction of many forms of activity-dependent synaptic modulation. Based on our recent evidence that in muscle cells and fibroblasts constitutive exocytosis is increased by elevating cytosolic Ca2+ levels, we hypothesize that Ca(2+) dependent exocytosis at the postsynaptic site may provide a mechanism for a localized, activity-dependent synaptic modulation. PMID- 8195795 TI - Blood markers in Alzheimer disease: subnormal acetylcholinesterase and butyrylcholinesterase in lymphocytes and erythrocytes. AB - In patients with the clinical diagnosis of Alzheimer disease (AD), we searched for systemic changes in components of the blood as a diagnostic tool. The acetylcholine-related enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were measured in plasma, erythrocytes, platelets and lymphocytes. Results did not show a general effect; notwithstanding, specific cell types presented alterations either in AChE or BuChE but not in both enzymatic activities. In AD patients, AChE of lymphocytes was reduced by 60% compared with the age-matched controls. However, when patients were divided, the sporadic but not the familial subgroup exhibited a significant reduction. In erythrocytes the BuChE activity was reduced by 45% in sporadic AD. The molecular forms of the lymphocyte AChE were characterized by velocity sedimentation. Both globular forms were subnormal, more so the tetrameric G4 AChE form than the G2 form. PMID- 8195796 TI - Magnetic resonance imaging in cerebrotendinous xanthomatosis: a prospective clinical and neuroradiological study. AB - We describe MRI findings in 13 persons with typical clinical, EEG, CT and biochemical features of cerebrotendinous xanthomatosis (CTX). MRI showed brain (13/13) and cerebellar (12/13) atrophy and diffuse white matter hypodensity (4/13) presumably reflecting sterol infiltration with demyelination. Focal lesions were rare (2/13). Mass effect, edema or enhancement were not observed. Treatment with chenodeoxycholic acid (CDCA) 750 mg/day orally improved neurological and biochemical abnormalities. MRI appears to be of little value in following improvement after treatment has begun. Otherwise, the MRI studies are very sensitive and useful in diagnosing early incomplete forms of CTX. PMID- 8195797 TI - Detection of circulating cerebral emboli using Doppler ultrasound in a sheep model. AB - We describe a validation study of a new technique for detecting circulating pathological cerebral emboli. Theoretically one would expect solid emboli to be detectable as high intensity signals on the Doppler waveform, and such signals have been reported in humans with potential embolic sources. Pathological cerebral emboli (thrombi, platelet aggregates and atheroma) were introduced into the proximal carotid artery of an in vivo sheep model, and their passage detected in the cerebral circulation using Doppler ultrasound. All of 74 emboli, with a maximum dimension as small as 0.24 mm, were detected as short duration high intensity signals. Smaller pathological emboli could not be made but glass microspheres as small as 5-20 micron resulted in high intensity signals. A significant positive correlation was found between embolus size and relative intensity increase of the embolic signal. A significant positive correlation was also found between embolus size and duration of embolic signal. This study demonstrates that detection of circulating cerebral emboli is possible in vivo. This technique may allow selection of patients at particularly high risk of cerebral embolisation so that they can be given specific prophylactic treatment. Analysis of the Doppler signal may give information on the size of the embolus, although using current signal analysis it is impossible to distinguish between the signals produced by say a larger platelet embolus or a smaller thrombus embolus. PMID- 8195798 TI - Auditory effects on the motor responses after magnetic cortical stimulation and on the H-reflexes in patients with Parkinson's disease. AB - The effects of sound on the responses in teh abductor pollicis brevis muscle after magnetic cortical stimulation and on the H-reflexes in the wrist and finger flexor muscles were examined. Magnetic cortical stimulation and electrical stimulation eliciting H-reflexes were conditioned by sound stimulation. This sound stimulation did not produce the electromyographic response by itself. In the control subjects, sound stimulation produced an increase of the motor responses after cortical stimulation at intervals of 100, 150, 200 and 250 ms. The increase was greater in the patients with Parkinson's disease (PD). In the control subjects, sound stimulation produced an increase of the H-reflexes at intervals of 50, 100, 150 and 200 ms. This H-reflex increase in the PD patients was less than in the normal subjects. The reticular system might play a role in the abnormal motor control system in PD patients. PMID- 8195799 TI - Hereditary motor and sensory neuropathy with myelin outfolding: clinical, genetic and neuropathological study of three cases. AB - We describe 3 patients affected by a congenital motor and sensory neuropathy with excessive myelin outfoldings (MOs). Clinical and electrophysiological features supported the diagnosis of hereditary motor and sensory neuropathy (HMSN). The genetic study failed to demonstrate either the duplication in chromosome 17p11.2 or the mutations at exons 1 and 2 of the myelin protein gene, PMP-22, recently observed in HMSN type Ia, and suggested an autosomal recessive (AR) inheritance. Sural nerve biopsy revealed a demyelinating process with prominent hypertrophic changes and excessive MOs formation. The percentage of MOs was significantly higher than in 3 age-matched HMSN Ia patients. MOs were morphologically and morphometrically different from tomacular-like thickenings of myelin. Myelin thickness was significantly lower than in the three HMSN Ia controls and linear regression showed a thinner myelin related to axon diameter. The reported cases demonstrate that HMSN with MOs is a well defined variant of HMSN and that a primary defect in the myelination process may be proposed as a possible pathogenic mechanism. PMID- 8195800 TI - The therapeutic effects of 4-methylcatechol, a stimulator of endogenous nerve growth factor synthesis, on experimental diabetic neuropathy in rats. AB - We investigated therapeutic effects of 4-methylcatechol (4-MC), a non-amine catechol compound, on streptozotocin (STZ)-induced diabetic neuropathy in rats. 4 MC is one of the potent stimulators of endogenous nerve growth factor (NGF) synthesis both in vitro and in vivo. Diabetic rats showed a statistically significant reduction in motor nerve conduction velocity (MNCV), mean myelinated axon diameter, and NGF content in the sciatic nerve during the experimental period of 8 weeks. The 4-MC treatment started 4 weeks after the STZ injection resulted in significantly greater NGF content, faster MNCV, and larger mean myelinated nerve fiber diameter and axon diameter than in untreated diabetic rats. These findings suggest that a decreased NGF level in the diabetic sciatic nerves may be involved in the pathogenesis of diabetic neuropathy and that 4-MC treatment could be useful for diabetic neuropathy. PMID- 8195801 TI - Familial hypokalemic periodic paralysis. Clinical, diagnostic and therapeutic aspects. AB - Five generations of a family with hypokalemic periodic paralysis (HOPP) were studied. Of the 120 screened family members, 64 were found to have HOPP of which 38 were suffering from attacks. In the other 26 the diagnosis was made on account of vacuolar myopathy, a reduced muscle fiber conduction velocity or the signs of permanent muscle weakness (PMW) in combination with (grand)children with attacks. Applying these criteria skipping of generations did not occur in this family. When defined properly, PMW was found in all patients at older age, independent of the previous occurrence of paralytic attacks. Dynamometry and muscle CT-scanning appeared valuable in the diagnosis and the progression of PMW. In 2 patients autopsy was performed. Characteristics vacuolization was found in the striated muscle tissue in various degrees. Heart and smooth muscle tissue were not involved. Therapy is limited. Potassium salts shortening and preventing the paralytic attacks are tolerated well. Acetazolamide is more effective in the prevention of the paralytic attacks, but is not tolerated very well. HOPP can be considered as a myopathy characterized by PMW at older age in all patients, combined with paralytic attacks in more than half the patients. PMID- 8195802 TI - A role for mast cells in the progression of Duchenne muscular dystrophy? Correlations in dystrophin-deficient humans, dogs, and mice. AB - Dystrophin deficiency has been shown to be the underlying cause of Duchenne muscular dystrophy. Although dystrophin-deficient homologous animal models have been identified (dog, mouse, and cat), the clinical expression of the biochemical defect is species-specific. Thus, while the genetics and biochemistry of Duchenne dystrophy is understood, the pathophysiological cascade leading to muscle weakness in only humans and dogs remains obscure. To begin to dissect the pathophysiology at the histological level, we undertook a systematic study of mast cells in normal and dystrophin-deficient muscle. Mast cells have been implicated in the development of fibrosis in other disorders, and progressive fibrosis has been hypothesized to mediate the failure of muscle regeneration in human and dog dystrophin deficiency. Our results show a strong correlation between mast cell content and localization, and the clinico-histopathological progression in humans, dogs and mice. The mast cell increases were disease specific: other dystrophic myopathies with normal dystrophin generally did not show substantial increases in mast cell content or degranulation. Our data suggest that mast cell accumulation and degranulation may cause the grouped necrosis characteristic of dystrophin deficiency in all species. PMID- 8195803 TI - Synthesis and secretion of transcobalamin II by cultured astrocytes derived from human brain tissue. AB - Astrocytes derived from human brain tissue secreted a single cobalamin (vitamin B12, Cbl) binding protein over a 4 day period in culture. Cycloheximide reversibly inhibited the release, and the binding protein was identified as transcobalamin II (TCII) based on molecular size, reaction with anti-human TCII antiserum, precipitation with 2.0 M ammonium sulfate and its ability to bind radioactive cyanocobalamin. It also enhanced the cellular incorporation of the vitamin. Our data show that cultured cells from human brain synthesize and secrete TCII and suggests that at least some of the TCII known to be present in cerebrospinal fluid may originate from within the central nervous system. PMID- 8195804 TI - Magnetic resonance imaging in monitoring the treatment of multiple sclerosis patients: statistical power of parallel-groups and crossover designs. AB - Serial brain magnetic resonance (MR) imaging detects active lesions 5-10 times more frequently than the occurrence of clinical changes in patients with early relapsing-remitting and secondary progressive multiple sclerosis (MS). Based on monthly unenhanced and gadolinium enhanced MR findings in 23 unselected and untreated patients, the power of an MS treatment trial was calculated, using MR imaging activity as the primary measure of outcome. It was shown that a 80% reduction in the number of active lesions (i.e. an efficacy of 80%) should be detected using a placebo-controlled parallel-groups design with a power of 80%, if either 2 x 20 patients are scanned monthly for 4 months, or 2 x 30 patients monthly for 2 months. Short to medium term studies of new experimental treatments in MS, using MR imaging as the primary outcome measure, provide considerable statistical power in small patient populations studied over a short period of time. PMID- 8195805 TI - Lipophilicity at pH 7.4 and molecular size govern the entry of the free serum fraction of drugs into the cerebrospinal fluid in humans with uninflamed meninges. AB - Physicochemical properties of drugs were related to their ability to enter the cerebrospinal fluid (CSF) in humans by reevaluation of previously reported studies. Either the quotients of the drug concentrations in CSF and serum at steady state (CCSFSS/CSSS) or, since in most cases CSF passage was studied after a short-term infusion, the ratios of the areas under the concentration-time curves in CSF and serum (AUCCSF/AUCS) were taken as measures of CSF passage. AUCS and CSSS were corrected for binding to serum proteins (AUCSf, CSssf). Of the drugs studied the quotient of the octanol/water partition coefficient at pH 7.4 (PC) as a measure of lipophilicity and the square root of the molecular weight (MW1/2) correlated with AUCCSF/AUCS (Spearman's rank correlation coefficient rS = 0.78, P < 0.01) and with AUCCSF/AUCSf (rS = 0.90, P < 0.01). PC.MW-1/2 was related to AUCCSF/AUCSf (or CCSFSS/CSssf, respectively) by the equation: AUCCSF/AUCSf = 0.96 + 0.091.1n(PC.MW-1/2). For 0.0001 < or = PC.MW-1/2 < or = 1.0 this function may be of value for the prediction of CSF penetration in humans when the physicochemical properties of a drug are known and when active transport or metabolism are negligible. PMID- 8195806 TI - Immunohistochemical localization of glutathione peroxidase in infarcted human brain. AB - This is the first report which demonstrates the presence of glutathione peroxidase in the autopsied brain of 5 patients without cerebral infarction and 21 patients with cerebral infarction by the indirect enzyme-labeled antibody technique with monoclonal antibody to human glutathione peroxidase. In 2 out of 5 patients without cerebral infarction, a weak reaction for glutathione peroxidase was demonstrated both in neurons and glia. In 6 patients who had died within 5 days after stroke, no staining was observed in infarcted brain tissue except in macrophages. In all 15 patients who had died more than 6 days after stroke, however, a reaction for glutathione peroxidase was demonstrated in the cytoplasm of glial cells in the marginal area around the infarction, and there was a patchy reaction in the cytoplasm of macrophages in the core lesion. These results suggest that glutathione peroxidase in glial cells of the marginal area around the infarction may play a protective role against lipid peroxidation after cerebral infarction, or alternatively, may be involved in the healing process after ischemia. PMID- 8195807 TI - Platelet mitochondrial function in Leber's hereditary optic neuropathy. AB - We report the effect of the 11,778 and 3460 base pair mitochondrial DNA mutations, found in Leber's hereditary optic neuropathy (LHON), on platelet mitochondrial respiratory chain enzyme activity. We measured respiratory chain enzyme activities in platelets from 4 patients with the 3460 mutation, 17 patients with the 11,778 mutation and compared them with those of 41 healthy age matched controls. We observed a 67% (P < 0.001) reduction in the mean NADH CoQ1 reductase (complex I) activity of the 3460 group compared to the control group. It has been shown previously that platelet mitochondrial biochemistry is affected by cigarette smoking. A significant reduction (25%, P < 0.03) in the mean complex I activity of the 11,778 group was only observed when the non-smokers within that group were compared to the non-smoking controls. The effect of smoking observed in this study may explain why previous workers have not observed a decrease in complex I activity associated with the 11,778 mutation. There was no significant change in the activity of complexes II/III or IV with either of these mutations. There was a significant increase (26%, P < 0.008) in citrate synthase (CS) activity with the non-smoking 11,778 group compared to the non-smoking control group, rising to 40% (P < 0.002) in those with this mutation who smoked. This reflects an increase in mitochondrial mass with the 11,778 mutation. This effect was not observed with the 3460 mutation even though the complex deficiency was much more severe. PMID- 8195808 TI - Platelet morphology in Parkinson's disease: an electron microscopic study. AB - There are no peripheral diagnostic markers for Parkinson's disease (PD). However, recent studies of platelets in PD patients indicate that mitochondrial and monoamine oxidase function may be abnormal. This investigation examines platelets in PD from a morphological standpoint utilizing transmission electron microscopy (EM). Fourteen PD patients (seven treated, seven untreated) and seven age matched controls had platelets separated from other blood components, fixed in a standardized fashion and examined by EM. Platelets (in the activated form because they were collected in glass tubes) were evaluated at magnifications of 15,000x and 40,000x. Abnormalities observed in treated and untreated PD patients included the presence of numerous large intracytoplasmic vacuoles formed from the open canalicular system. Morphometric examination performed at 40,000x magnification indicated that the mean area of vacuoles and the cytoplasmic volume percent of platelets occupied by vacuoles were significantly greater in PD (p < 0.05) than controls. However, differences observed between treated and untreated PD groups suggest that these changes could be caused by the disease or the treatment or both. No abnormalities were found in relation to mitochondria, storage granules and glycogen. From EM assessment, we conclude that platelets in PD are morphologically abnormal. PMID- 8195809 TI - Astrocytes in Alzheimer's disease express immunoreactivity to the vaso constrictor endothelin-1. AB - The avidin-biotin peroxidase complex method and a polyclonal antiserum were used to investigate the distribution of endothelin-1-like immunoreactivity of cerebral astrocytes in autopsy cases of Alzheimer's disease compared with controls. The cases of Alzheimer's disease presented numerous astrocytes with intense endothelin-1-like immunoreactivity of the cell body often extending into the finest ramifications of the cell processes. Absorption of the antiserum by the corresponding antigen eliminated this immunostaining. The immunoreactive astrocytes were most consistently present in the subcortical white matter of the cerebral hemispheres and the folia of the cerebellum. The immunoreactive cells were often located in small clusters close to blood vessels. Five of the seven cases showed immunoreactive astrocytes in the molecular layer of the cerebral cortex and three of the seven cases presented regions in which immunoreactive astrocytes appeared to be located in the periphery of plaques. The pons contained small groups of immunoreactive astrocytes in five of the cases. The cerebellum had such cells in six of the seven investigated patients. Immunoreactive astrocytes were very rare in control cases without cerebral disease. Many nerve cells in the cerebral neocortex, hippocampus, cerebellum and pons of Alzheimer cases and controls exhibited endothelin-1-like immunoreactivity. Oligodendrocytes and endothelial cells of blood vessels of controls and Alzheimer cases did not show such immunoreactivity. The expression of endothelin-1-like immunoreactivity in astrocytes of Alzheimer's disease probably reflects an increased content of endothelin-1. If endothelin-1 is released from such astrocytes it may reach smooth muscle cells of the intracerebral blood vessels and disturb micro circulation since this compound is a most powerful vasoconstrictor peptide. PMID- 8195810 TI - Cerebrovascular and neurological disorders associated with antiphospholipid antibodies in CSF and serum. AB - Paired serum and cerebrospinal fluid (CSF) samples from 70 patients with inflammatory and non-inflammatory neurological diseases, as well as 10 sera from patients with primary antiphospholipid syndrome (PAS), six of which presented with cerebrovascular ischemic syndromes, were studied for the presence of anticardiolipin antibodies (ACA) of the G and M classes. PAS sera and some selected paired CSF and serum specimens, were also analyzed for the presence of anti-phosphatidylserine (PS) and anti-phosphatidylethanolamine (PE) antibodies. High levels of IgG and IgM ACA were synthesized intrathecally only in patients with neurosyphilis. Patients with other infectious or inflammatory neurological diseases very rarely showed detectable levels of ACA in serum and/or CSF. ACA were found not only in patients with untreated PAS but also in the serum of 3/7 patients with migraine, thus confirming a relationship between ACA and vascular disorders. The search for PS and PE antibodies disclosed that in PAS patients the serum titers of these antibodies mirrored ACA IgG and IgM titers, while they were never found in the CSF. PMID- 8195811 TI - A time course study of the alterations in the development of the hamster cerebellar cortex after destruction of the overlying meningeal cells with 6 hydroxydopamine on the day of birth. AB - This study is a chronological analysis of 6-hydroxydopamine-induced alterations in development of the hamster cerebellar cortex. This treatment destroys the overlying meningeal cells, the sequelae of which include (i) a thinning of the external granular layer over the folial apices and a thickening in the region of the prospective fissures, reflecting a retardation of the growth of the cerebellar cortex, accompanied by displacement of the normally superficialmost GFAP-positive external granular layer cells into deeper parts of the external granular layer; (ii) a retardation of multiplication of Golgi epithelial cells which colonize the rostral third of the Purkinje cell layer so that their numbers decrease in the rostralmost folia; (iii) disturbed morphological and biochemical differentiation of the Golgi epithelial cells and their processes, the growing radial Bergmann glial fibres which detach from the pial surface and branch within the external granular layer, causing a failure in endfeet formation at the superficial glia limitans, loss of characteristic radial morphology, with the adoption of a multipolar form, and normal or increased GFAP expression and decreased S-100 expression; (iv) fragmentation of the external granular layer beyond P5 to P7 with loss of the regular lamination and foliation of the cerebellar cortex, characterized by a completely random distribution of fragments of Purkinje cell layer, molecular zone and internal granular layer. We conclude that the destruction of meningeal cells interferes with the establishment and stabilization of both the external granular layer and the secondary radial glial scaffold composed of Golgi epithelial cells, whose proliferation, growth and differentiation is subsequently disturbed. The failure to stabilize the external granular layer and to form a normal secondary radial glial scaffold is, in turn, responsible for the disruption of the regular laminar deposition of the neurons of the cerebellar cortex. PMID- 8195812 TI - Meningeal cells organize the superficial glia limitans of the cerebellum and produce components of both the interstitial matrix and the basement membrane. AB - We have investigated the factors controlling both the morphological transformation of glial processes into endfeet and the deposition of extracellular matrix molecules into the overlying basement membrane by destroying meningeal cells over the hamster cerebellum by 6-hydroxydopamine administration on the day of birth. We report that within 24 h of destruction of meningeal cells, the concentrations of fibrillary collagens types I, III and IV in the glia limitans externa and the associated basement membrane molecules laminin, collagen type IV, and fibronectin are greatly diminished, resulting in the development of focal gaps in the basement membrane. The immunohistochemical integrity of the basement membrane is restored within 3 days over those surfaces of the folial apices where meningeal cells reappear. Likewise, the fibrillary collagens of the associated interstitial matrix are re-established in the same amounts as in controls. However, meningeal cells remain permanently absent from fissures and all extracellular matrix molecules tested disappear from rostral cerebellar folia covered by the anterior medullary velum. Moreover, the glial endfeet make up the superficial glia limitans only on folial apices, while they disappear from the fissural surfaces. In primary cultures, meningeal cells produce the fibrillary collagens type I, III, and VI, and the matrix molecules fibronectin and laminin, collagen type IV, nidogen, and heparansulphate proteoglycan. These findings indicate that meningeal cells (i) produce molecular components of both the interstitial matrix and the basement membrane, and (ii) are involved in the morphological transformation of glial fibres into the endfeet which constitute the superficial glia limitans. PMID- 8195813 TI - The ganglion cell response to optic nerve injury in the cat: differential responses revealed by neurofibrillar staining. AB - The early responses of cat retinal ganglion cells to axotomy have been examined using neurofibrillar and Nissl-stained wholemounts. We were interested to learn whether the enhanced neurofilament expression, seen in a number of neuronal systems, was also present in different neuronal populations of the cat retina and could be used to study the distribution of these cells. We found that beta ganglion cells degenerate very rapidly after axotomy with the nuclei becoming pyknotic within a few days. Few beta cells showed increased neurofibrillar staining of the dendrites. The cell body degenerated prior to any visible degenerative changes in the axon. A proportion of the alpha and gamma ganglion cells degenerated in the first two to three weeks after axotomy. The alpha cells underwent markedly enhanced neurofibrillar staining of their dendrites prior to degeneration. The Nissl material of the cell bodies diminished as the cells degenerated but we have not observed pyknotic nuclei. The dendritic trees of some axotomised gamma cells were also revealed by the neurofibrillar stain three weeks after axotomy. These results show that retinal ganglion cells do not degenerate by a dying back process. We suggest that the rapid degeneration of the beta ganglion cell population comes about by excitotoxic cell death, a consequence of their large glutamatergic input from bipolar cells. The degenerating beta ganglion cells have the morphological appearance of cells undergoing apoptosis. PMID- 8195814 TI - Monoclonal antibodies specific for endoplasmic membranes of mammalian cochlear outer hair cells. AB - Monoclonal antibodies were raised in vitro against an antigen associated with the lateral cisternal membranes of outer hair cells. Two of the antibodies were class IgM and one of these retained its specific reactivity in tissue fixed with aldehydes and embedded in the resin LR White. Immunogold labelling for electron microscopy showed that the antigen was closely associated with the membranes rather than the cytoplasmic or lumenal regions of the cisternae. The third antibody was an IgG. All three weakly labelled a protein band with an apparent molecular weight of about 60 kD on a Western blot. The antibodies did not cross react with any other cell in the organ of Corti, including the inner hair cells. Furthermore, they showed no cross-reactivity with skeletal muscle, kidney, gut, brain, skin, blood or retina from the guinea pig. The results suggest that the lateral cisternae in outer hair cells may be functionally different from those of inner hair cells. The antibodies may provide useful markers for outer hair cells in studies of hair cell regeneration. PMID- 8195815 TI - The development of the radial glial scaffold of the cerebellar cortex from GFAP positive cells in the external granular layer. AB - We have reinvestigated the origin and genesis of the radial glia of the cerebellar cortex in the hamster using three astroglial markers, vimentin, GFAP, and S-100 protein antibodies. On embryonic day 12 (E12), before the emergence of the external granular layer, the cerebellar anlage is traversed from the ventricle to the pial surface by a primordial radial glial scaffold which is vimentin-positive, but GFAP and S-100 negative. With the formation of the external granular layer on E13, a few GFAP positive cells appear among the unstained external granular layer cells. First seen within the germinal trigone and caudalmost part of the external granular layer, they then develop rostrally, amongst the cells of the expanding external granular layer, proliferating adjacent to the basement membrane. Beginning on E15, cells that are positive for the S-100 protein also appear within the external granular layer and the molecular zone. In later stages, S-100 is strongly expressed in Golgi epithelial cells, so we have considered it to be a marker for these cells. By contrast, the primordial radial glial cells were not stained with this marker. On the day of birth (E16/PO) many S-100 positive cells also appear at intermediate levels between the EGL and the Purkinje cell plate. They are unipolar and bear a single radial process that is directed towards the pial surface. The caudorostral appearance of S-100-positive cells firstly in the external granular layer, then in the molecular zone and finally in the Purkinje cell plate is identical to the temporal sequence of development of these layers, and suggests that S-100 positive cells are at first integral constituents of the external granular layer, but later descend through the molecular zone, to colonize the Purkinje cell plate. Here they proliferate and ultimately differentiate into Golgi epithelial cells, their numerous short radial glial processes traversing the molecular zone and the external granular layer to fill the interstices between the primordial radial glial fibres. At birth, S-100-positive Golgi epithelial cells have progressively colonized the Purkinje cell plate from the germinal trigone rostrally, up to a region midway between primary fissure and anterior medullary velum and, between P2 and P3, the rostralmost part of the cerebellum has become populated. GFAP- and S-100-positive cells remain in the external granular layer up to the end of the first postnatal week. In the same interval, the number of Golgi epithelial cells and Bergmann glial fibres increases rapidly in the expanding cerebellar cortex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8195816 TI - Phobic postural vertigo: a first follow-up. AB - Seventy-eight patients with phobic postural vertigo (PPV) and 17 patients with psychogenic disorder of stance and gait (PSG) were asked to evaluate their condition 6 months to 5.5 years after their original referral and short-term psychotherapy. Two results seem most important: (1) PPV had a favorable course with a 72% improvement rate (22% of patients becoming symptom free), whereas the majority of patients with PSG (52%) remained unchanged; (2) the majority of patients with PPV experienced complete remission or considerable improvement even if their condition had lasted between 1 and 20 years prior to diagnosis. Complete remission of PSG was observed only if the disorder has been present less than 4 months; there was no improvement if it had lasted longer than 2 years. PPV can be defined as a distinct clinical entity with a relatively benign course. It can be reliably diagnosed on the basis of typical features. PMID- 8195817 TI - Disease-specific patterns of neuronal loss in the spinal ventral horn in amyotrophic lateral sclerosis, multiple system atrophy and X-linked recessive bulbospinal neuronopathy, with special reference to the loss of small neurons in the intermediate zone. AB - The ventral horn cells of the fourth lumbar segment were morphometrically analysed in six cases of amyotrophic lateral sclerosis (ALS; there common forms and three pseudopolyneuritic forms), six of multiple system atrophy (MSA) with autonomic failure, four of X-linked recessive bulbospinal neuronopathy (X-BSNP), and seven age-matched autopsy cases of non-neurological disorders. In the common form of ALS, large and medium-sized neurons of the medial and lateral nuclei were markedly lost; small neurons in the intermediate zone were slightly diminished but fairly well preserved. In the pseudopolyneuritic form of ALS, marked loss was present in the large and medium-sized neurons, and in the small neurons located in the intermediate zone as well. In the MSA, in contrast to ALS, there was a marked reduction in small neurons in the intermediate zone, and large and medium sized neurons of the medial and lateral nuclei tended to be preserved. In X-BSNP, large and medium-sized neurons were almost completely lost and small neurons were also markedly depopulated. These findings indicated that the pattern of neuron loss in the ventral horn is distinct among these diseases depending on size, location and function of the ventral horn cell population. These disease-specific patterns of neuron loss suggest a difference in the process of neuronal degeneration of ventral horn cells among the disease examined. PMID- 8195818 TI - Human spumaretrovirus antibody reactivity in multiple sclerosis. AB - The role of human spumaretrovirus (HSRV) infections in the pathogenesis of multiple sclerosis (MS) was investigated with recombinant HSRV env-specific enzyme-linked immunosorbent assay. The presence of HSRV antibodies was determined in pairs of serum and cerebrospinal fluid (CSF) samples from 60 MS patients. In 7 of these patients serial serum and CSF samples were obtained in relation to the clinical activity of the disease during a period of 2 years. No increased antibody reactivity was demonstrable in the MS population compared with 14 aseptic meningitis patients, 50 blood donors and 16 healthy controls. Slightly elevated levels of antibodies were demonstrable in serum and/or CSF in 4 MS patients but also in 1 patient with aseptic meningitis, 1 blood donor and 1 child. No marked serum or CSF HSRV antibody fluctuation was observed in the MS patients followed longitudinally. Thus, this study does not support the involvement of HSRV in the pathogenesis of MS. PMID- 8195819 TI - Abnormal dystrophin expression in patients with limb girdle syndromes. AB - Clinical differential diagnosis between Becker muscular dystrophy (BMD) and limb gridle muscular dystrophy (LGMD) may be difficult because the BMD clinical phenotype tends to overlap with other limb girdle syndromes, especially with LGMD. Therefore we studied the expression of dystrophin, the protein product of the Becker and Duchenne muscular dystrophy gene, in muscle biopsy specimens of 30 patients (18 males, of whom 15 represented spradic cases, and 12 females) diagnosed as having LGMD according to traditional clinical, electrophysiological and histological criteria. For dystrophin analysis, six different monoclonal antibodies directed against different epitopes of the dystrophin molecule were used. Immunocytochemically, five of the 30 LGMD patients (17%) showed abnormal dystrophin staining patterns diagnostic of BMD. Western blotting in these five patients, all sporadic cases, showed dystrophin of reduced size and/or abundance. Analysis of blood or muscle DNA using multiplex polymerase chain reaction revealed deletions in the dystrophin gene in three of the five. Thus, 5 of 15 (33%) sporadic male patients previously thought to have LGMD were identified as having BMD. PMID- 8195820 TI - Changes in peripheral blood lymphocyte subset frequencies in myasthenia gravis patients are related to immunosuppression. AB - Surface antigens on peripheral blood lymphocytes from myasthenia gravis patients were investigated. The expression of DR+ and CD8+/DR+ T lymphocytes was increased and the expression of CD4+ T cells reduced. Neither thymectomy, clinical condition nor anti-acetylcholine receptor antibody titre correlated with any of the changes in peripheral blood lymphocyte subsets observed. However, immunosuppressive therapy correlated with the significant reduction in CD4+ and CD2+/CD4+ T cells in these patients. PMID- 8195821 TI - An open-randomized clinical trial of selegiline in amyotrophic lateral sclerosis. AB - Based on the hypothesis that free radicals play a general role in the neurodegenerative process in motor neuron disease, we tested selegiline in a group of patients affected by amyotrophic lateral sclerosis (ALS) to examine whether it might modify the progression of the disease. Patients were admitted if they were 25-80 years old and had a confirmed diagnosis of ALS with symptoms lasting no longer than 24 months. Patients with familial ALS, pure progressive bulbar palsy, primary lateral sclerosis or progressive muscle atrophy were excluded; a total of 111 patients were recruited. Fifty-three patients were randomly assigned to receive the drug (selegiline 10 mg/day orally for 6 months) and the remaining 58 were considered ALS controls. Mortality was similar in the two groups (4 and 5 patients respectively), though the difference was not statistically significant. Among the survivors, mean MRC and Norris disability scores and forced vital capacity were fairly similar in the two groups at all times and no statistically significant difference between treated and untreated patients was found. The results did not change when the data were related to age, duration and characteristics of onset of the disease. The rate of progression was significantly more rapid in patients with bulbar symptoms in both groups. Our data do not show any significant effect of selegiline in modifying the progression of ALS. PMID- 8195822 TI - Pregnancy and multiple sclerosis--a 3-year prospective study. AB - A prospective study of the level of disability, severity and distribution of relapses in 15 women with multiple sclerosis prior to, during and up to 3 years following pregnancy was undertaken. The pregnant group was compared with 22 nulliparous women attending the same clinic and matched for age and severity and duration of disease. In the pregnant group, relapses were more frequent and severe than expected values during the first 6 months post partum, but were below expected values 6-24 months post partum. Over the total study period, therefore, there were no significant differences in relapse number, Expanded Disability Status Score or functional scores between the two groups. Babies born during the study showed normal distributions of weight and head circumference. PMID- 8195823 TI - Oculomotor abnormalities and MRI findings in idiopathic cerebellar ataxia. AB - Extensive oculomotor testing and quantitative MRI evaluation was performed in seven patients with idiopathic cerebellar ataxia without extracerebellar symptoms (IDCA-C) and in ten patients with additional extracerebellar symptoms (IDCA-P). The most severe oculomotor deficits were disturbed smooth pursuit, optokinetic nystagmus and suppression of the vestibulo-ocular reflex (VOR). The symptoms correlated well and consistently with the amount of atrophy of the flocculus and the dorsal vermis. These correlations, however, were not specific, and deficits also correlated with the amount of atrophy of other cerebellar structures. No correlation was found between saccade velocity and brainstem atrophy or between saccade metrics and atrophy of the dorsal vermis. Although patients with IDCA-P had more severe oculomotor deficits than patients with IDCA-C, the pattern of the oculomotor disturbances was the same for both groups. Thus, eye movement analysis alone is not sufficient to distinguish between patients with pure cerebellar ataxia and those with additional extracerebellar symptoms. PMID- 8195824 TI - Serum prolactin response to repetitive epileptic seizures. AB - We measured postictal prolactin (PRL) levels during repetitive seizures in 14 patients (10 men and 4 women) suffering from epilepsy with focal and/or secondarily generalized seizures. Between two and six seizures occurred per patient (mean 2.7). The interveral between seizures was 15 min and 8 h 40 min (mean 3 h 32 min). Five of the 14 patients showed a marked postictal PRL rise after each seizure (i.e. concentrations above 700 microU/ml for women, 500 microU/ml for men). In the remaining 9 patients there was no detectable rise in PRL. A decrease in PRL did not occur in any of the 14 patients. In those patients who had shown a marked PRL increase after the first seizure, the PRL continued to rise in subsequent seizures. Unlike previous investigations, these results show that repetitive epileptic seizures are not necessarily followed by a decrease in postictal PRL levels. A decrease in PRL response is known to occur if there is progression to status epilepticus. PMID- 8195825 TI - Benign and secondary progressive multiple sclerosis: a preliminary quantitative MRI study. AB - In a preliminary study, we compared by means of quantitative magnetic resonance imaging (MRI) methods (1) the T2 values and the decay characteristics of chronic brain lesions, (2) the T2 values of normal-appearing frontal white matter (NAWM) and (3) brain lesion volumes in patients with benign and secondary progressive multiple sclerosis (MS) in order to evaluate the mechanisms underlying the development of disability. Eleven clinically definite MS patients with either benign MS (n = 5) or secondary progressive MS (n = 6) were studied. Fifty-two chronic lesions (identified by comparison with MRI scans obtained at least 12 months previously) were identified. The mean T2 of large lesions (cross-sectional area greater than 41 mm2) and of the NAWM was similar in both clinical groups. However, small lesions had higher mean T2 values (P < 0.01) in the benign group, probably at least in part because of partial volume effects. Analysis of large lesions revealed biexponential T2 relaxation in 6 of 8 "secondary progressive" and in 2 of 16 "benign" lesions, perhaps indicating a greater degree of axonal loss in large lesions of patients with secondary progressive MS. Patients with secondary progressive MS had higher (although not significant) total and infratentorial lesion loads than those of the benign group. These preliminary findings suggest, but do not establish, that variations in the extent, site and pathological nature of lesions may all contribute to different patterns of disease evolution in MS. PMID- 8195826 TI - Intracranial haematomas following bone marrow transplantation. AB - Intracranial haemorrhage (ICH) is a known grave complication of leukaemia and has been described post mortem following bone marrow transplantation (BMT). Ante mortem following BMT, the incidence and significance of ICH is not well defined. The records of 471 bone marrow transplantation recipients over 11 years at the Hadassah University Hospital Bone Marrow Transplantation Department were reviewed. The relevant data of all patients with ICH were analysed. A resolute diagnostic and treatment protocol for subdural haematomas had been employed. The indication for transplantation in 273 of the patients was leukaemia. Thirteen of these patients developed subdural haematomas within 42 days of the transplant, and nine of these haematomas were bilateral. None of the 198 patients with other malignancies or nonmalignant indications for BMT (predominantly aplastic anaemia and beta thalassaemia major) had subdural haematomas. One thalassaemia patient and three leukaemia patients had intracerebral haematomas. There was no mortality or major morbidity from the subdural haematomas, which were all successfully resolved. In contrast, all of the patients with intracerebral haematomas consequently died. Subdural haematomas occur in approximately 5% of patients with leukaemia following BMT, but the clinical outcome is relatively benign. Intracerebral haematomas are a sporadic, lethal complication following BMT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195827 TI - History and future of antimicrobial diaminopyrimidines. AB - Numerous pyrimidine and purine analogs were synthesized in the late forties in G.H. Hitchings' group as potential nucleic acid antagonists. Several key observations finally led to the selection of pyrimethamine as an antimalarial and trimethoprim (TMP) as an antibacterial agent: i) 2,4-diamino-5-substituted pyrimidines interfered with folic acid utilization rather than being thymine antagonists as expected; ii) a large degree of selectivity could be obtained by suitable substitution and non-toxic diaminopyrimidines with preferential antimicrobial activity were found; iii) the identification of dihydrofolate reductase (DHFR) as the specific target for aminopterin and methotrexate in 1958 and for TMP in 1965, and the diversity of this enzyme in different species. Although several diaminopyrimidines were initially tested as monotherapies in clinical trials, the pronounced synergism between some of these new compounds and sulfonamides seen against Plasmodium was finally also applied in the development of TMP. Its combination with sulfamethoxazole later proved one of the most successful agents ever developed. Further milestones in the application of antimicrobial DHFR inhibitors were the introduction of TMP alone in 1972, the launch of a new combination of tetroxoprim, a close TMP-analog, with sulfadiazine, and the successful clinical trials with brodimoprim, which proved clinically efficacious and safe with once-daily low dose monotherapy. Efforts to discover new antimicrobial DHFR inhibitors have recently intensified. DHFRs from important gram-positive problem organisms such as S. aureus, S. epidermidis have been cloned and sequenced, as well as DHFRs from opportunistic pathogens such as P. carinii, T. gondii, and of mycobacteria. DHFR crystal structures from several of these organisms are available to aid rational inhibitor design.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195828 TI - Molecular aspects and mechanism of action of dihydrofolate reductase inhibitors. AB - Derivatives of tetrahydrofolate (FH4) are involved in a variety of biosynthetic reactions. Inhibition of the enzyme dihydrofolate reductase (DHFR) depletes the available tetrahydrofolate and blocks the formation of thymidylate, purines, the amino acids methionine and glycine, and several other cell constituents. Lack of thymidylate disrupts DNA synthesis and cell growth ceases. Many folate analogues are competitive inhibitors of DHFR, and while some classes show no selectivity, suitably substituted diaminopyrimidines are several thousands times more active against bacterial than mammalian DHFR and are thus effective and safe antibiotics. The ease of isolation, stability and low molecular weight of DHFR has facilitated its study at a molecular level. Considerable knowledge has been accumulated about the interactions of inhibitors with the protein chain in and around the active site, but despite the availability of many sequences and several crystal structures the exact details of how subtle variations of inhibitor structure result in such large differences in affinity for the enzyme are not yet clear. PMID- 8195829 TI - Structure-activity relationships of dihydrofolate reductase inhibitors. AB - Structure-activity relationships of antibacterial dihydrofolate reductase inhibitors are reviewed. A short introduction is followed by a more detailed review of developments since 1980. The design of site directed inhibitors based on data from X-ray crystallographic, NMR spectroscopy and molecular graphic studies is discussed. The development of quantitative structure-activity relations is surveyed from a historical point of view and these are contrasted with more recent alternative approaches. Conclusions are reached regarding possible future developments. PMID- 8195830 TI - Basis of selectivity of antibacterial diaminopyrimidines. AB - The basis for the high affinity and selectivity of trimethoprim [2,4-diamino-5 (3',4',5'-trimethoxybenzyl)pyrimidine, TMP] and several close structural analogues is reviewed. Methoxy group substitution on the benzyl group of 2,4 diaminobenzylpyrimidine markedly affects both Escherichia coli dihydrofolate reductase (DHFR) Ki values and in vitro antibacterial activity. TMP is several hundred-fold more potent than the unsubstituted benzylpyrimidine, and the monomethoxy and dimethoxy analogues are of intermediate activity. However, equilibrium dissociation constants determined in the absence of cofactor (NADPH) show that the binding of these diaminobenzylpyrimidines in the enzyme-inhibitor binary complex is considerably weaker and does not vary among the compounds. Thus, the TMP binding affinity of E. coli DHFR is increased by NADPH in the ternary complex, and this increased affinity (cooperativity) varies with methoxy group substitution. In contrast, mouse DHFR has a weaker binding affinity for diaminobenzylpyrimidines, and none of the analogues show strong NADPH cooperative effects. The difference in the magnitude of NADPH/TMP cooperativity between bacterial and mammalian DHFR is an important factor in selectivity. The E. coli enzyme binds TMP more avidly in binary complex, and an additional selectivity factor of 30-fold arises from differences in cooperativity. Although the X-ray crystal structures of bacterial and vertebrate DHFR have been studied extensively, no single hypothesis convincingly explains the molecular basis of TMP selectivity. However, information on the three-dimensional structure of the enzyme has been used to rationally design novel, high-affinity inhibitors. PMID- 8195831 TI - Preclinical toxicology and safety pharmacology of brodimoprim in comparison to trimethoprim and analogs. AB - The toxicology and safety pharmacology of brodimoprim (Ro 10-5970), a new dihydrofolate reductase inhibitor for antimicrobial chemotherapy, are reported. The toxicity is compared to trimethoprim and other dihydrofolate reductase inhibitors of the trimethoprim type. In safety pharmacological tests brodimoprim showed no significant activity in the cardiovascular, autonomic neuroeffector or central nervous systems. Effects on urine volume and sodium and potassium excretion were not noted. The acute toxicity of brodimoprim after oral administration is low. In repeated dose studies in rats, oral doses up to 50 mg/kg/day were generally well tolerated. In the baboon no toxic effects were seen even at repeated doses up to 150 mg/kg/day; on the other hand the dog was found to be particularly sensitive to treatment as 20 mg/kg/day were poorly tolerated. Target organ systems included central nervous system, liver, red blood cell parameters and thyroid gland. Doses up to 100 mg/kg/day were not teratogenic or embryotoxic in rabbits. However, treatment with 100 mg/kg/day in reproductive toxicity studies in rats induced effects on fetal/litter weight, survival of offspring and litter size and increased the incidence of skeletal variations and malformed offspring. No mutagenicity was found in the tests performed with brodimoprim. In comparison brodimoprim shows the typical toxicity known for trimethoprim and analogs. In pyrimethamine toxic effects occurred at considerably lower doses than in the other compared compounds. PMID- 8195832 TI - Comparative antibacterial spectrum of trimethoprim and brodimoprim. AB - Brodimoprim is a new 2,4-diaminobenzylpyrimidine that selectively inhibits bacterial and resistance plasmid dihydrofolate reductases to a similar or greater extent than trimethoprim. Brodimoprim reaches equivalent levels in the serum as trimethoprim for the same dosage regimens but, unlike trimethoprim, brodimoprim has a long half-life. Brodimoprim has a similar antibacterial spectrum to trimethoprim against bacterial species normally sensitive to this class of drugs although it is not active against aerobic bacteria that are normally inherently trimethoprim-resistant, such as Pseudomonas spp. Against a range of strains of the Enterobacteriaceae trimethoprim was slightly more active, although in an in vivo murine model brodimoprim had a significantly better cure rate. Brodimoprim was 2-4-fold more active against several strains of Neisseria, Nocardia, Vibrio cholerae, Bacteroides and other anaerobes. In particular the MIC90 values of brodimoprim for Clostridium and Fusobacterium spp were lower than those of trimethoprim. PMID- 8195833 TI - In vitro and in vivo results of brodimoprim and analogues alone and in combination against E. coli and mycobacteria. AB - New diaminodiphenylsulfone inhibitors of dihydropteroate synthase are described with increased inhibitory activity against mycobacteria and plasmodia, whereas their side effect of methemoglobin formation could be suppressed. The optimization of diaminobenzylpyrimidines, inhibitors of dihydrofolate reductase, led to derivatives with increased inhibitory effect against mycobacteria, especially M. leprae and plasmodia. Some of these derivatives show autosynergism. Finally the combination of brodimoprim (BDP) and dapsone (DDS) was developed for the treatment of leprosy. First clinical trials in Paraguay and Ethiopia show that combinations of BDP/DDS and BDP/DDS plus rifampicin were highly effective and may become an alternative multi-drug therapy for the treatment of leprosy. The tolerance of the regimens used was generally good. PMID- 8195834 TI - In vitro brodimoprim activity on nosocomial bacterial strains. AB - The activity of brodimoprim, a new diaminopyrimidine, against 385 recent clinical isolates of Gram-positive cocci and Gram-negative bacilli was in vitro tested by the disk sensitivity test (DST) of Bauer et al. with disk concentration of 2.5 micrograms and by the agar dilution method. The postantibiotic effect (PAE) and the postantibiotic leukocyte killing enhancement (PALE) were determined on selected pathogens. The MICs were determined with Muller Hinton II agar (BD) and a multipoint inoculator (Denley A 400); thymidine phosphorylase (0.08 U/ml) was added to the test agar. Brodimoprim was very active against S. pyogenes (27), Salmonella sp. (30), methicillin susceptible S. aureus (36) and E. faecalis (34). The geometric means (GM) of MICs ranged from 0.08 to 0.63 and % of resistance from 0.0 to 14.7. Higher MICs (GM from 1.02 to 2.67) were shown against Citrobacter sp. (32), Klebsiella sp. (27), E. coli (36), methicillin-resistant S. aureus (33), Enterobacter sp. (32), Proteus sp. (31) and methicillin-susceptible coagulase negative staphylococci (34); resistant strains ranged from 18.7 to 41.2%. The in vitro activity against methicillin-resistant coagulase-negative staphylococci (33) (72.7% of resistance to brodimoprim) was very low. Regression analysis, obtained correlating the results of MICs with those of agar diffusion, shows that the resistant strains have a diameter less than 11 mm, the intermediate ones a diameter of 11-13 mm and susceptible strains a diameter greater than 13 mm. The PAE was determined using the Abbott AVANTAGE system. Strains were exposed to brodimoprim (1/4 x MIC - 4 x MIC range) for 2 or 6 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195835 TI - In vitro brodimoprim activity on bacterial strains. AB - The antibacterial activity of brodimoprim (BDP) was compared to that of trimethoprim (TMP) and to 4 other antibiotics (3 beta-lactams and one macrolide). The 237 tested strains were selected predominantly among bacteria isolated from respiratory tract infections: 133 Gram-negative bacilli and 98 Gram-positive cocci. The study included: determination of minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of all antibiotics of the study for all isolates; kinetics of bactericidal activities for selected susceptible strains; correlation between MICs and inhibition zones (standard agar diffusion technique) of BDP (regression line). The results of the study showed: [1] no significant difference between in vitro activities of BDP and TMP against all tested strains; [2] low MICs of both drugs for Haemophilus influenzae, Legionella pneumophila, Staphylococcus aureus (methi-S and methi-R), Streptococcus pneumoniae (peni-S), streptococci and enterococci; [3] kinetics of bactericidal activities indicating 4 log decrease of inoculum size with BDP for Staph. aureus, S. pneumoniae, H. influenzae, within 7 hours; [4] correlation was established between inhibition zones and MICs of BDP, with a coefficient of correlation r = 0.88 for 182 strains. In conclusion, BDP exhibited in vitro antibacterial and bactericidal activities at least equal to that of reference drugs against most respiratory pathogens; BDP was superior to comparators against methi-R staphylococci and enterococci. PMID- 8195836 TI - Inhibition of bacterial adhesion by sub-inhibitory concentrations: brodimoprim vs trimethoprim. AB - There is accumulating evidence that sub-inhibitory concentrations (sub-MICs) of many antibiotics are not without effect on bacteria and even though they do not kill bacteria, they are still able to interfere with some important aspects of bacterial cell function. The aim of the present study was to investigate the effect of sub-MICs of brodimoprim and trimethoprim on Escherichia coli and Staphylococcus aureus adhesiveness to human mucosal cells. Sub-MICs of brodimoprim down to 1/32 MIC (0.03 microgram/ml) significantly reduced the E. coli adhesion to human buccal epithelial cells and this inhibition was significantly higher than the corresponding pattern for trimethoprim. Adhesion of S. aureus was significantly reduced down to 1/16 MIC for both brodimoprim and trimethoprim but no significant differences resulted between the two patterns. 2,4 Diaminopyrimidines and related structures have a high affinity for the enzyme dihydrofolate reductase and this causes a reduction in the synthesis of essential purines, thus reducing also DNA and the synthesis or expression of surface adhesins. PMID- 8195837 TI - Epidemiology of resistance to diaminopyrimidines. AB - Resistance to trimethoprim emerged in Enterobacteriaceae and later in other Gram negative and Gram-positive bacteria within two years of the clinical introduction of the drug. Resistance is borne in many different replicons often present in multiply-resistant epidemic bacteria. The incidence of trimethoprim resistance is highly variable, depending upon methodology, type of patients, local epidemiology: this can be illustrated by the high variation of trimethoprim resistance among Salmonella, Shigella or MRSA in various countries and by the incidence of resistance in penicillin-resistant Streptococcus pneumoniae. PMID- 8195838 TI - Trimethoprim and brodimoprim resistance of gram-positive and gram-negative bacteria. AB - Trimethoprim and brodimoprim act by selectively inhibiting bacterial dihydrofolate reductase. There are a number of mechanisms by which bacteria can develop resistance to these agents. These include thymineless mutation, impermeability, alteration in chromosomal dihydrofolate reductase and the plasmid encoded production of an additional dihydrofolate reductase which is insensitive to inhibition by antifolate agents. Clinically the most important of these is the plasmid-encoded production of additional dihydrofolate reductases and such resistance is found in both gram-positive and gram-negative species. These plasmid-encoded enzymes were initially divided into a number of classes based principally on their biochemical profiles. More recently sequence analysis has been used to study these proteins and thus the classification of dihydrofolate reductases now also takes into account sequence information. The number of plasmid-mediated dihydrofolate reductases has increased markedly in recent years. Whilst this probably results from the continuing evolution of resistance it can also be partly attributed to more discriminatory methods for studying these enzymes. PMID- 8195839 TI - Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines. AB - Trimethoprim is the best known inhibitor of bacterial dihydrofolate reductase. Initially, this was always combined with sulphamethoxazole. It was later combined with other sulphonamides (eg. sulphamoxole, sulphadiazine or sulfametopyrazine), but the sulphonamide moiety as a contributor to clinical efficacy was increasingly questioned. Thus, in 1979 (in UK) trimethoprim alone was introduced. Justification for the combination was based on: (a) synergy occurs in vitro (b) bactericidal activity, while the two components are bacteriostatic (c) the emergence of resistance was claimed to be lower. However, these claims were not substantiated by studying the microbiological and pharmacokinetic properties of trimethoprim and the sulphonamides, but most importantly by the results of clinical trials. These show that in most indications, trimethoprim alone is as good, cheaper and causes considerably fewer adverse events than use with a sulphonamide. For urinary infections most agree that monotherapy is best. In respiratory infections diaminopyrimidines have relatively poor activity against important pathogens, eg pneumococci and especially Moraxella catarrhalis. It could be argued in these case that the addition of a sulphonamide may increase therapeutic efficacy. This can only be resolved by large clinical trials. In brucellosis and gonorrhoea, where sulphonamides are more microbiologically active than diaminopyrimidines, it is likely that combination with another antibiotic is needed. However, too much reliance must not be placed on extrapolating from trimethoprim to other diaminopyrimidines; conclusions should be drawn from work using the other compounds. PMID- 8195840 TI - Pharmacokinetics of brodimoprim. AB - Brodimoprim is a dihydrofolate reductase inhibitor which is highly active against a broad spectrum of gram-negative and gram-positive bacteria. Single dose pharmacokinetics and dose proportionality of this drug were studied in healthy volunteers who received orally 150, 400 and 600 mg. Multiple dose pharmacokinetics were evaluated after administration of an oral loading dose of 400 mg followed by daily maintenance doses (tau = 24 h) of 200 mg on seven consecutive days. Plasma and urine samples were collected up to 4 days after dosing and analyzed for unchanged drug by an HPLC-assay with fluorescence detection. Approximately 4 hours after single oral administration of 150, 400 and 600 mg, Cmax-values of 1.5, 3.3 and 6.2 mg/l were observed. The corresponding AUC values after these doses were 73, 156 and 290 mg.h/l, respectively, and reflect a good dose proportionality in the investigated range. In the postdistributive phase an elimination half-life of 32-35 h was determined which justifies once daily administration. Total plasma clearance (Cls/F) reached approximately 40 ml/min and renal clearance was approximately 3 ml/min. Approximately 80% of the dose was recovered from urine, but only 4-7% could be identified as unchanged drug. With faeces less than 10% of the dose was excreted predominantly as parent drug. Hence, metabolic degradation is the dominant elimination process of brodimoprim. The apparent volume of distribution (V beta/F) was high (approximately 1.5 l/kg) and reflects the good penetration of brodimoprim into most body fluids and tissues. During multiple dosing, the pharmacokinetic parameters of brodimoprim remained unchanged, and induction or inhibition of the drug metabolizing/eliminating enzymes can be excluded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195841 TI - Pharmacokinetics of brodimoprim in special populations. AB - The pharmacokinetics of brodimoprim have been investigated after single oral dose administration in children, in healthy adults, and elderly subjects, as well as in patients with mild renal failure (creatinine clearance 40-70 mL/min) or liver insufficiency (Child-Pugh grade A or B). The plasma half-life increased moderately with age. The percent brodimoprim bound to plasma proteins, 93%, was identical in renally impaired patients and in healthy controls but decreased to 90% or less in liver insufficiency. The apparent distribution volume and clearance were much higher in children than in adults. Urinary excretion of unchanged brodimoprim amounted to 5-10% of the administered dose. The steady state pharmacokinetics of brodimoprim has also been investigated in elderly subjects (400 mg loading dose followed by 7 days 200 mg once daily). There was no significant modification of elimination half-life and of clearance upon repeated dosing. Renal excretion of brodimoprim and hydroxy metabolite at steady-state reached 9% and 14% per 24 hours in the elderly, compared to 9% and 24% in young adults. The accumulation factor reached 3.3 +/- 0.4 and 2.7 +/- 0.3 respectively. PMID- 8195842 TI - Pharmacokinetic profile of brodimoprim: oral bioavailability and penetration into interstitial fluid. AB - The bioavailability of brodimoprim tablets given orally is 80-90%; their relative bioavailability compared to an aqueous solution is 100%. Penetration of brodimoprim to suction skin blisters is 73 +/- 8%. The elimination half-life is longer from blisters than from serum. The relative stability of extravascular concentrations suggests that, with adequate dose sizes, dosage may be once daily, and even only once every second day. PMID- 8195843 TI - Brodimoprim concentrations in bronchial mucosa, bronchial secretions and middle ear effusions. AB - Brodimoprim, a structural analogue of trimethoprim, is a long acting broad spectrum antibacterial agent characterized by a good pharmacokinetic profile, allowing once daily (OD) administration. The aim of this study was to investigate the penetration of brodimoprim into bronchial mucosa, bronchial secretion and middle ear effusion, in order to evaluate the efficacy of the antibiotic in respiratory tract infections. The study was performed in patients affected by chronic bronchitis having to undergo diagnostic bronchoscopy (n = 26), in patients affected by exacerbation of chronic bronchitis with purulent or mucopurulent secretions (n = 10), and in patients affected by otitis media with eardrum perforation (n = 28). Patients were orally treated with 400 mg of brodimoprim (single dose). Samples of serum, bronchial mucosa, bronchial secretion and middle ear effusion were collected in the separate series of patients above mentioned, at different times after drug administration. Brodimoprim determinations were performed by a microbiological method using Bacillus subtilis ATCC 6633 as test microorganism. Brodimoprim reached the highest concentration in serum 4 h after administration and was still detectable at 24th hour. In bronchial mucosa and in bronchial secretion the peaks were reached at 8th hour (9.7 +/- 5.3 mg/kg and 4.57 +/- 1 mg/l respectively) while in middle car effusion were reached at 4th hour (4.8 +/- 2.5 mg/l). The drug was still detectable at antibacterial concentrations, both in infected fluids and in tissue samples, 24 hours after administration (4.3 +/- 1.8 mg/kg in bronchial mucosa; 3.5 +/- 0.66 mg/l in bronchial secretions; 3 +/- 0.6 mg/l in middle ear effusion).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195844 TI - Pharmacokinetics and blister fluid penetration of brodimoprim in adults. AB - We investigated the pharmacokinetic properties of brodimoprim (B), a new diaminopyrimidine, including its penetration into suction blister fluid (SBF) after a single or multiple oral dose in 15 patients with a mean age of 61.5 +/- 9.3 yrs, suffering from respiratory tract infections with normal renal and hepatic function. Patients were divided into 3 groups of 5 cases each, according to treatment plan: Group I = B 400 mg single dose day 1; Group II = B 400 mg qD day 1 and 200 mg qD days 2 to 4; Group III = B 200 mg BID day 1 and 200 mg qD days 2 to 4. Concentrations were determined microbiologically using B. subtilis ATCC 6633 as the test organism with a lower limit of sensitivity of 0.37 mg/l. With a single oral dose of 400 mg (Group I) a computed serum Cmax of 2.9 +/- 0.6 mg/l was observed 5.6h after administration, with a elimination half-life (t1/2 beta) of 32.3 +/- 4.1 h. In SBF a mean peak of 1.9 +/- 0.6 mg/l was reached after 6h with a t1/2 beta of 34.7 +/- 5.4 h and a penetration index (Pl), obtained by the AUCSBF/AUCs percent ratio of 61%. With multiple doses serum peak concentrations increased significantly, while the time to reach the peak (Tmax) was shorter (3.7-4.2 h) than after a single dose. Main kinetic parameters, such as t1/2 beta, mean residence time (MRT), elimination rate constant (Kel) and AUC, were significantly higher in Group II and III patients than in Group I cases. Similar differences were observed among the main SBF kinetic parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195845 TI - In vitro effects of brodimoprim on human polymorphonuclear leukocyte functions. Preliminary results. AB - The in vitro effects of brodimoprim and trimethoprim on the functions of human polymorphonuclear (PMN) leukocytes have been studied comparatively evaluating chemotaxis, phagocytosis and production of superoxide anion. No significant effects of both diaminopyrimidines on chemotaxis and phagocytic activity of PMNs have been observed while both brodimoprim and trimethoprim enhanced the oxidative burst. A synergistic activity between the host immune system and the direct antimicrobial action of brodimoprim may occur while using this diaminopyrimidine in vivo. PMID- 8195846 TI - Brodimoprim: therapeutic efficacy and safety in the treatment of bacterial infections. AB - The clinical efficacy and safety of brodimoprim has been studied by numerous investigators. In the trials reviewed 2291 cases were entered. Of these 2214 were evaluable for efficacy and 2277 for safety. Brodimoprim has been found to exhibit good therapeutic efficacy in upper and lower respiratory tract infections, in bacterial gastroenteritis and in typhoid fever. Response rates in the above indications were reported to be in the range of 85-100% for upper respiratory tract infections, 84-92% for lower respiratory tract infections, 97-100% for bacterial gastroenteritis and 95-100% for enteric fever. In controlled studies these response rates were in the same range as those obtained with standard drugs (ampicillin, amoxicillin, cephalosporins, erythromycin, doxycycline, chloramphenicol). Of the 2277 patients assessable for safety 1429 had received brodimoprim and 848 received a comparative agent. In the brodimoprim group, the overall incidence of clinical adverse events occurring in patients during treatment was 12.7%. The majority of adverse events reported were nausea and vomiting, skin reactions, and CNS reactions. The incidence and pattern of adverse events caused by comparative drugs was similar to those caused by brodimoprim, with the exception of doxycycline which generated fewer clinical adverse events than the other regimens. Brodimoprim in single daily doses may be considered as a highly efficacious and well tolerated antibacterial agent against a broad range of bacterial infections. PMID- 8195847 TI - A multicenter comparative study of brodimoprim and amoxicillin therapy in the treatment of tonsillopharyngitis in adults. AB - STUDY OBJECTIVE: To compare the efficacy and safety of brodimoprim (BDP) with those of amoxicillin (AMX) in patients with acute bacterial pharyngitis/tonsillitis. DESIGN: Randomized controlled study. SETTING: Hospital and general practices in Austria, Germany and Switzerland. PATIENTS: 519 adult patients of both sexes aged 12 to 75 years. INTERVENTION: Patients were allocated to an 8- to 12-day treatment with BDP (400 mg loading dose followed by 200mg once a day) or AMX (750mg t.i.d). MAIN OUTCOME MEASURES: Resolution of clinical signs/symptoms and negative bacterial examination at completion of therapy. RESULTS: Clinical cure/improvement rate of 97.8% and 94.8% in respectively the BDP and the AMX group. Bacterial eradication in 87.7% of the cases treated with BDP and 88.3% of those receiving AMX. Very good/good tolerability in 85.2% BDP- and 82.8% AMX treated patients. PMID- 8195848 TI - Efficacy and tolerability of brodimoprim in respiratory tract infections. AB - Brodimoprim is a new diaminopyridine derivative suitable for oral therapy which shows good in-vitro activity against most Gram-positive and Gram-negative pathogens. The efficacy and tolerability of brodimoprim in acute lower respiratory tract infections was tested in controlled clinical trials in comparison with different classes of antibiotics. Acute bacterial infections or infective exacerbations of chronic obstructive bronchitis were included in the studies. Brodimoprim in a single dose was compared to different oral treatments which included co-trimoxazole (trimethoprim 160 mg+sulphamethoxazole 800 mg every 12 hours) and erythromycin (600 mg three times a day). In the studies criteria of efficacy such as daily temperature curve, intensity and frequency of cough, degree of dyspnea, intensity of thoracic pain, difficulty of expectoration, sputum production, thoracic semiology were examined. Brodimoprim was more effective than cotrimoxazole and erythromycin at the end of the treatment, induring a more significant and prompt reduction of axillary temperature, daily sputum volume, degree of dyspnea. There was no difference among treatments in the mean period of therapy to obtain the resolution of the infective process (8 days on average). Brodimoprim had a significantly lower percentage of side effects during the treatment in comparison with cotrimoxazole or erythromycin. Hence brodimoprim was better accepted by patients. PMID- 8195849 TI - Efficacy and tolerability of brodimoprim and roxithromycin in acute sinusitis of bacterial origin in adults. AB - In two ear, nose and throat (ENT) divisions, 74 patients affected by acute sinusitis of bacterial origin were selected and, after randomization in two balanced groups following an open parallel group design, assigned to treatment with brodimorprim and roxithromycin. At the beginning, after 3 days, 7 days and at the end of treatment the following symptoms were evaluated, using a four-step score: intensity of facial pain, headache, nasal stiffness, hyposmia, nasal secretion. The mean treatment period was 8.7 days. Tolerability was evaluated through registration and analysis of side effects and laboratory blood tests. The comparison between groups showed a better activity of brodimoprim on facial pain, headache, nasal stiffness and nasal secretion. The presence of resistant bacterial strains was greater in the group treated with roxithromycin (30.8%) when compared with the brodimoprim group (12.5%). Side effects were reported in 5 patients treated with brodimoprim and in 3 patients in the control group. Lab tests did not show serious variations. PMID- 8195850 TI - Brodimoprim in maxillary sinusitis. AB - Recent studies on bacteriological findings in chronic maxillary sinusitis show a great variety of aerobic as well as anaerobic germs. For these reasons adequate chemotherapy has to support the necessary surgical procedure. In this study, the author reports about 60 adult patients suffering from chronic maxillary sinusitis. All of them had to undergo surgical treatment by the Caldwell-Luc procedure. Postoperatively, 30 of them were treated with brodimoprim, the others with doxycycline for 7 days. Bacteriological investigations have been performed during and at several days after surgery. At the same time, a number of laboratory data and the complications observed were registered. In this way, a comparative study of the two antibiotic drugs concerning the therapy of chronic maxillary sinusitis was established. PMID- 8195851 TI - Efficacy and tolerability of brodimoprim in otitis. AB - Eighty adult patients affected by acute bacterial otitis media were selected and randomized into two balanced groups of treatment: 1) brodimoprim 200 mg tablets at the dosage of 2 tablets in single dose on the first day and one tablet on the following days; 2) josamycin 500 mg tablets at the dosage of 3 tablets/day. The average duration of treatment was 8 days: all patients completed the trial. The symptoms were evaluated by score method (on the 3rd, 7th and on the last day of therapy) and a thermometric curve was made daily. Microbiological examination of the exudate was performed in the patients with auricular discharge (28), at the beginning of the treatment and 7 days after the end of therapy. The tolerability was assessed through registration of side effects. Brodimoprim resulted more effective in the reduction of hypoacusis and tinnitus; other symptoms demonstrated higher percentage reductions in the group under brodimoprim therapy. Bacteriological exams were negative at the second checkup, except in 6 patients (3 per group). Side effects were reported in 5 patients (12.5%) treated with brodimoprim and in 9 (22.5%) treated with josamycin. Abnormal values in laboratory tests were not observed. PMID- 8195852 TI - Brodimoprim in acute respiratory tract infections. AB - Brodimoprim was studied in the treatment of acute respiratory tract infections in hospitalized, basically healthy, military conscripts. Its efficacy and tolerance were compared to those of doxycycline in a clinical randomized double-blind trial. 60 pts. were divided into two equally large groups. One group received brodimoprim, 400 mg as a loading dose followed by 200 mg daily, for 10 days. The other group received doxycycline, 200 mg as a loading dose followed by 100 mg daily, for 10 days. In the brodimoprim group, 23 patients (77%) were cured, 5 patients (16%) improved and 2 patients (6%) were considered failures. In the doxycycline group, 26 patients (87%) were cured, 3 patients (10%) improved and 1 patient (3%) did not respond. The only side effect in the whole study was moderate diarrhea in 1 patient in the brodimoprim group. Clinically and according to the normalization of laboratory values, the two drugs tested were equally effective. PMID- 8195853 TI - Efficacy and tolerability of brodimoprim in pediatric infections. AB - Brodimoprim is a long acting broad spectrum antibacterial agent. It is a new selective inhibitor of bacterial dihydrofolate reductase, structurally related to trimethoprim. The aim of the present study was to investigate the efficacy and tolerability of brodimoprim (10 mg/kg on the first day, 5 mg/kg/die onward) in the treatment of upper respiratory tract infections in children (age range: 2-14 years). This open group comparative study was performed either in 68 children affected by bacterial pharyngotonsillitis (37 treated with brodimoprim, 31 with erythromycin 560 mg/kg/8 hours) or in 50 patients affected by otitis media (25 treated with brodimoprim, 25 with amoxicillin/clavulanic acid 50 mg/kg/12 hours) or in 52 patients affected by acute sinusitis (25 treated with brodimoprim, 27 with amoxicillin/clavulanic acid 50 mg/kg/12 hours). All patients were clinically evaluated before admission, during the trial and 48 hours after the last dose of antibiotic. At the same time blood and secretion samples were collected for hematology/biochemistry and microbiological assays. A total of 170 subjects were treated and 141 patients demonstrated a clinical recovery/improvement following the treatment period, with approximately the same recovery rate (83%) among the groups. The bacteriological response was evaluated in 169 subjects. Eradication of pathogens was documented in 27 subjects treated with brodimoprim and 28 with erythromycin in the pharyngotonsillitis group, in 22 subjects treated with brodimoprim and 16 with amoxicillin/clavulanic acid in the otitis group and in 17 subjects treated with brodimoprim and 20 with amoxicillin/clavulanic acid in the sinusitis group. The overall eradication in brodimoprim treated patients was 77% in comparison with 76% of eradication obtained in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195854 TI - A randomized, open, comparative study of brodimoprim versus erythromycin in patients with acute tonsillitis or bronchitis. AB - The objective of the study was the comparison of the efficacy and tolerability of brodimoprim to those of erythromycin in children with acute tonsillitis or bronchitis. 50 children aged 0.5 to 9.3 years were included in the study, 25 treated either with brodimoprim or with erythromycin. The evaluation of the therapeutic response was based exclusively on clinical criteria. In the brodimoprim group the therapy was successful in 24 patients (one failure), in the erythromycin group the therapy was also successful in 24 children (one failure). Side effects: three patients treated with brodimoprim reported adverse reactions (stomatitis, vomiting, skin rash), whereas only one patient in the erythromycin group developed a skin rash. CONCLUSION: both therapeutic regimens were equally effective against bronchitis and tonsillitis in children. The tolerability was good in both groups. PMID- 8195855 TI - Efficacy and tolerability of brodimoprim in pharyngotonsillitis in children. AB - 160 children with an average age of 9 years (range 6-15) affected by acute bacterial tonsillitis, were selected and assigned, following an open, parallel group design to: a) brodimoprim at the dose of 10 mg/kg on the first day, in single administration, and of 5 mg/kg on the following days; b) cotrimoxazole suspension, at the dosage of 6 mg of trimethoprim/kg/day, in two daily administrations; c) amoxicillin with clavulanic acid suspension (amoxi clavulanate) 50 mg/kg every 12 hours. Quantity of pharynx and tonsillar exudate, pharynx pain, dysphonia and dysphagia were checked at the basal time, 3rd, 7th and at the last day of therapy. These symptoms were evaluated using a four-step rating scale. The evolution of body temperature was measured at two different times (1 and 5 o'clock p.m.), until the end of treatment, foreseen five days after disappearance of fever. Microbiological evaluation through a pharynx swab was performed at the beginning and at the end of therapy. Side-effects were registered during all the observation period. Lab-tests were carried out at the enrollment and at the end of treatment. The frequency and intensity of symptoms decreased significantly in all treatment groups. In comparison with amoxi clavulanate, the brodimoprim group showed an earlier improvement (3rd day) of the clinical situation and a significantly better regression of pharynx exudate (p < 0.01), pharynx pain (p < 0.05) and dysphonia (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195856 TI - Efficacy and tolerability of brodimoprim in bacterial otitis media in children. Controlled study versus cefaclor. AB - 78 pediatric patients affected by acute otitis media were selected and randomized into two balanced groups of treatment: brodimoprim, at the dosage of 200 mg once a-day on the first day and of 100 mg once-a-day on the following days, and cefaclor at a dosage of 40 mg/Kg/day in three doses. Brodimoprim resulted more efficacious in the reduction of symptoms, especially hypoacusis and tinnitus (p < 0.05 between treatments); tympanometry showed a higher number of normalizations in the brodimoprim group, without significant differences between treatments. Both drugs resulted active against most of isolated bacterial strains. Side effects were reported in 4 patients treated with brodimoprim and in 6 patients in the control group. PMID- 8195857 TI - Respiratory infections in children: when is brodimoprim indicated? AB - Respiratory infections are the most common infection in children. They differ remarkably according to age, bacteria and viruses. Therefore a careful history of outbreak, age, former infections, involvement of surroundings, symptoms, etc are essential. The present study included 50 children, aged between 0.3 and 12 yrs, all treated ambulatorily. 21 received brodimoprim (B) and 29 erythromycin (E). Indications were: tonsillitis, bronchitis, otitis media, sinusitis and scarlet fever. Dosages were: B was given 10 mg/kg body weight (b.w.) initially followed by 5 mg/kg b.w., once-a-day. The duration of treatment varied between 4 and 14 days (mean 8.3 days). E was given 30.50 mg/kg b.w. 3 times per day; duration 4 to 14 days (mean 8.6 days). Overall results were: in group B:12 cures, 5 improvements, 3 failures; 1 not assessable. In group E: 20 cures, 8 improvements, 1 failure. Side effects: in group B: vomiting (1), skin reaction (2), discontinuation (2); in group E: skin reaction (1), diarrhea (5), diarrhea+vomiting (1); discontinuation (2). The differences in efficacy and tolerability in the two groups are not statistically significant. The improved compliance with a single versus t.i.d. dosages has to be taken into account. PMID- 8195858 TI - Assessment of mechanical function as an adjunct to myocardial perfusion/metabolism emission tomography studies. PMID- 8195859 TI - Quantifying aspiration in scintigraphic deglutition testing: tissue attenuation effects. AB - Scintigraphic studies for determining aspiration associated with swallowing have ignored error due to differential gamma attenuation in the patient by the various regions of the body. This study sought to estimate the magnitude of that error, and to assess the feasibility of providing individual attenuation corrections based on clinical data. METHODS: Relative attenuation for the pharynx, thorax and abdomen were determined from physical measurements employing an anthropomorphic phantom and 45 adult human subjects. A small sealed radioactive source of 2.5 mCi of 99mTc was placed inside the phantom at various locations within the upper digestive tract and respiratory system, and relative count rates determined via static scans with a gamma camera. Similar data for human subjects was obtained from clinical swallowing testing using a bolus of 2.5 mCi of 99mTc in 10 cc of water. RESULTS: The ratios representing relative counts were highly similar between the phantom and average human data. Test-retest replication of results was good for the abdominal reference and pharynx ratios--less so for the thorax. A procedure is described for estimating accuracy of percent aspiration calculation based on group data, using normalization coefficients derived for separate anatomical regions in the subglottic respiratory system. CONCLUSIONS: Error in percent aspiration calculation will depend on the amount and location of aspirate. Individual subject corrections based on the type of clinical data studied should be attempted with caution. PMID- 8195860 TI - Quantification of aspiration: methodological and clinical perspectives. PMID- 8195861 TI - Treatment of metastatic prostate carcinoma with radiolabeled antibody CC49. AB - A Phase II trial of 75 mCi/m2 131I-anti-TAG-72 high-affinity antibody CC49 was studied in 15 patients with hormone-resistant metastatic prostate cancer. METHODS: Patients had adequate renal, liver and hematopoietic function. No previous cytotoxic chemotherapy was allowed and previous radiation was limited to 20% of the active bone marrow. RESULTS: No acute adverse reactions occurred, but all patients had evidence of an immune response to CC49 by 4 wk. Six of 10 symptomatic patients had bone pain relief, but no patients met the radiographic or PSA criteria for objective response. Positive imaging of bone and/or soft tissue lesions was noted for 13 of the 15 patients. CONCLUSIONS: CC49 had a high frequency of tumor localization with evidence of anti-tumor effects (pain relief). PMID- 8195862 TI - The lag phase of gastric emptying: clinical, mathematical and in vitro studies. AB - The lag phase of gastric emptying reflects, in large measure, the clinically important milling function of the stomach, but there is little agreement on the best way to acquire, analyze and characterize lag phase data of gastric emptying studies. METHODS: Twenty normal volunteers were fed a standard 99mTc-sulfur colloid scrambled egg and toast breakfast and imaging data were acquired at 15 min intervals in both anterior and posterior projections with the subject seated. RESULTS: In a significant percentage of the subjects, the stomach count rate rose above the initial count rate, even with geometric mean correction. We attributed the count rate rise to meal self-absorption and conducted mathematical and in vitro experiments, the results of which supported this thesis. Attempts at modeling the data with power exponential fits were unsuccessful in many cases and were complex, nonintuitive and of limited clinical utility. Accordingly, gastric emptying rates were determined by simple linear regression from geometric mean data. The starting index (the time at which the regression line equalled 100%) was calculated to reflect the lag phase. Normal ranges were determined for men and women. CONCLUSION: Our method of test performance is simple, eliminates confounding variables and provides results with intuitive meaning and with direct clinical relevance. PMID- 8195863 TI - Immunoscintigraphy of Pneumocystis carinii pneumonia in AIDS patients. AB - The diagnosis of Pneumocystis carinii pneumonia (PCP) currently relies upon cytological demonstration of the organism in sputum or bronchoscopy specimens. The purpose of this study was to develop a radiolabeled monoclonal antibody (Mab) against Pneumocystis carinii (P. carinii) and to evaluate its use for imaging PCP. METHODS: We studied 16 HIV-infected patients with pneumonia in order to evaluate a new Mab-based imaging method for diagnosing PCP. Most patients were managed for opportunistic pneumonia associated with AIDS, including standard cytological tests, and, in all cases, intensive chemotherapy. Prior to the clinical study, the Mab raised to P. carinii was shown to react with human P. carinii but not with rat P. carinii or human white blood cells. RESULTS: After labeling a 1-mg Mab Fab' fragment with 30 mCi of 99mTc, the presence or absence of PCP could be confirmed in six of seven or seven of eight assessable patients, respectively, by external photoscanning within 24 hr. This shows a sensitivity of 85.7% and a specificity of 86.7%. CONCLUSION: Our findings suggest that PCP can be diagnosed by a noninvasive imaging method employing a small dose of a 99mTc labeled Mab showing specificity for the infectious organism, since patients with P. carinii-free pneumonia were correctly negative in 87.5% of cases. Rapid diagnosis and organ-localization of other infectious lesions with organism specific, radiolabeled Mabs may be feasible. PMID- 8195864 TI - PCP, AIDS and nuclear medicine. PMID- 8195865 TI - Pneumocystis carinii pneumonia presenting as focal bibasilar uptake on gallium scan during aerosolized pentamidine prophylaxis. AB - Radionuclide imaging with gallium is commonly performed in the evaluation of patients with suspected Pneumocystis carinii pneumonia (PCP) and is known to be highly sensitive for detection of PCP. We present a patient with acquired immunodeficiency who developed PCP in the bases of both lungs while on aerosolized pentamidine prophylaxis. A gallium scan demonstrated focal uptake in the lung bases, a pattern generally not associated with PCP, and was extremely useful in guiding bronchoscopy. An aerosol ventilation scan performed after complete resolution of the clinical illness demonstrated prominent ventilatory defects in the lung bases corresponding to the regions of previous gallium uptake. We speculate that the underlying ventilatory abnormality may have contributed to poor drug delivery to the lung bases. Pneumocystis carinii pneumonia must be considered with any focal area of gallium accumulation in patients receiving aerosolized pentamidine. PMID- 8195866 TI - Hyperperfusion and early technetium-99m-HMPAO SPECT appearance of central nervous system toxoplasmosis. AB - Three correlative 99mTc-HMPAO brain SPECT studies were performed on an AIDS patient from the early stage of a CNS toxoplasma lesion to its resolution after specific therapy. A hyperactive area in the right parieto-occipital lobe appeared in the first SPECT study, matching the heterogeneous T2-weighted image with Gd DTPA enhancement reported on MRI. Both studies were performed 3 days after the onset of neurological symptoms when no abnormalities were found on a CT scan. This fact can be explained by the hyperemia that occurs in the acute stage of inflammation. Three months later, along with clinical improvement under specific treatment, both MRI and brain SPECT were normal. No hypoperfusion was seen in SPECT images, probably because the necrotic phase of the toxoplasma lesion was not reached in this case. PMID- 8195867 TI - Unilateral absence of right-lung perfusion with normal ventilation on radionuclide lung scan as a sign of aortic dissection. AB - A case of aortic dissection with unilateral absence of right-lung perfusion and normal ventilation on radionuclide ventilation/perfusion (V/Q) lung scan is presented with a review of the literature. Anticoagulation or thrombolytic therapy for presumed pulmonary embolism may be catastrophic if the clinical syndrome and V/Q scan appearance are instead due to aortic dissection. With this V/Q scan appearance, these therapies should not be instituted unless pulmonary embolism is diagnosed by pulmonary arteriography. PMID- 8195868 TI - Cholescintigraphy in the diagnosis of Rotor syndrome. AB - In three patients with chronic conjugated hyperbilirubinemia who carried the diagnosis of Rotor syndrome, 99mTc-HIDA cholescintigraphy was performed. In these patients, the liver was either not visualized or it was seen very faintly with slow liver uptake, persistent visualization of the cardiac blood pool and prominent kidney excretion. The present observation emphasizes the contribution of cholescintigraphy in the diagnosis of Rotor syndrome. PMID- 8195869 TI - Atypical renal artery stenosis in a renal transplant: diagnosis by radionuclide techniques. AB - A case of a cadaveric kidney transplant recipient who developed progressively severe renal failure within 3 mo of transplantation secondary to renal artery stenosis is presented. The patient was primarily hypotensive and Doppler ultrasound showed normal flow. The problems in diagnosing this unusual case are reviewed. The findings on serial radionuclide studies eventually led to consideration of the correct diagnosis. PMID- 8195870 TI - Noninvasive imaging of c-myc oncogene messenger RNA with indium-111-antisense probes in a mammary tumor-bearing mouse model. AB - The c-myc oncogene is amplified in leukemia and solid tumors, thus making the c myc messenger RNA (mRNA) a suitable target for following the progression of malignancy by noninvasive imaging with radiolabeled antisense pharmaceuticals or radiolabeled antisense oligodeoxynucleotide (RASON) probes. Considering the higher stability of phosphorothioate over phosphodiester, the probe stability and tumor localization was compared with both derivatives. METHODS: The 15-mer oligonucleotide sequence was synthesized, aminolinked [sense and antisense phosphodiester (O) and monothioester (S)] and coupled with diethylenetriamine pentaacetate (DTPA)-isothiocyanate and aliquots were lyophilized to make a DTPAAHON kit. The radionuclide 111In was chelated to DTPAAHON derivatives, and free 111In was separated by gel filtration. The radiolabeled antisense and sense probes were injected intravenously in mammary tumor-bearing BALB/c mice (1 x 10(6) cells, 8 days postinoculation). RESULTS: The highest uptake was observed at 2 hr with both thio and oxo derivatives of RASON probes, and small tumors could be imaged noninvasively. Tumor uptake and tumor/blood and tumor/muscle ratios for the sense probe (control) were significantly lower (p < 0.001) than those of the antisense probe. CONCLUSION: The radiolabeled antisense probe may provide a new sensitive tool for noninvasive imaging of c-myc oncogene mRNA for a variety of malignant tumors at an earlier stage. PMID- 8195871 TI - Making sense out of anti-sense: challenges of imaging gene translation with radiolabeled oligonucleotides. PMID- 8195872 TI - Active and passive mechanisms of [fluorine-18] fluorodeoxyglucose uptake by proliferating and prenecrotic cancer cells in vivo: a microautoradiographic study. AB - In this study, [18F]FDG uptake mechanisms were investigated in neoplastic cells during cell proliferation and cell death. METHODS: Detailed analysis was performed on mouse tumor models of different growth rates using [18F]FDG, [6 13H]thymidine [3H]Thd (a precursor of DNA synthesis) and [125I]bovine serum albumin ([125I]BSA) (a marker of diffusion) with autoradiographic and histopathologic techniques and electron microscopy. RESULTS: The three compounds, [18F]FDG, [3H]Thd and [125I]BSA, showed different heterogeneous patterns of distribution within tumor tissue sections in neoplastic and non-neoplastic cellular elements. The uptake of [18F]FDG by prenecrotic (or necrobiotic) tumor cells surrounding focal necrotic cell debris was 1.5 to 2.3 times higher than that of viable tumor cells. Prenecrotic cells did not retain trapped [18F]FDG; therefore, the uptake was considered to be nonmetabolic. Inconspicuous cell membrane, vesicular cytoplasmic organelles and condensed nuclear chromatin were remarkable findings in the prenecrotic cells. A comparison of viable tumor cells in tumors undergoing different growth rates showed that the ratio of [18F]FDG uptake was similar to that of [3H]Thd uptake in each S-phase cell. Fluorine-18 FDG showed a cell cycle dependency, with a higher uptake observed in cells in G0/G1 and G2 phases of the cell cycle compared with the S and M phases. CONCLUSION: A passive mechanism of [18F]FDG uptake may exist in the necrobiotic/prenecrotic or hypoxic/anoxic cells in tumors. However, the discordance of [18F]FDG and [3H]Thd uptake may be the result of the different cell cycle dependency of tracer uptake in the same tumor. PMID- 8195873 TI - Evaluation of myocardial infarct size before and after reperfusion: dual-tracer imaging with radiolabeled antimyosin antibody. AB - Antimyosin antibody is a specific marker of myocardial necrosis that is based on the loss of integrity of the sarcolemmal membrane. Because antimyosin can be labeled with several different radiotracers, gamma imaging performed with antimyosin labeled with two different radionuclides can be used to quantify infarct size before and after an intervention such as reperfusion. METHODS: Twelve open-chested anesthetized dogs were evaluated both at the end of 1.5 hr of occlusion of the left anterior descending coronary artery and following reperfusion. Antimyosin Fab radiolabeled with either 123I or 111In was injected by intracoronary administration over 3 min at the end of the occlusion interval, and the coronary sinus was drained continuously for 7 min to prevent recirculation of the antibody. One hour after reperfusion, a second injection of antimyosin Fab (labeled with a different isotope from the first) was administered as before. Six dogs were given intracoronary trifluoperazine (150 micrograms/kg of body weight) simultaneously with reperfusion, and another six dogs received saline as the control. The infarct size in grams before and after reperfusion was assessed by antimyosin antibody uptake in ex vivo images of 1-cm thick slices of the hearts. The mean infarct sizes before (W1) and after (W2) reperfusion were then calculated as the percent of infarcted myocardium/ventricular myocardial mass. RESULTS: There was a significant increase in the mean percent infarct size after reperfusion in the control group (W2 = 16.73 +/- 4.0, W1 = 14.92 +/- 3.88; p = 0.029). The mean infarct size was uniformly smaller with trifluoperazine intervention (W2 = 12.33 +/- 2.03, W1 = 16.34 +/- 2.78; p = 0.004). The difference between the mean change in the infarct sizes in the two groups was highly significant (p = 0.002). CONCLUSION: Dual imaging of the extent of myocardial necrosis before and after an intervention (reperfusion) in the same animal demonstrated the utility of antimyosin imaging to document changes in the extent of necrosis. PMID- 8195874 TI - Food and Drug Administration grants approval for 131I MIBG. PMID- 8195875 TI - Visions and revisions: viewpoints on nuclear medicine and health care reform. Part 2: Practice guidelines. PMID- 8195876 TI - No "pure" nukes. PMID- 8195877 TI - Paralimbic hypoperfusion in unipolar depression. AB - METHODS: Relative regional cerebral blood flow was measured with SPECT using 99mTc-hexamethylpropyleneamine oxime in 13 patients with severe unipolar depression that was nonresponsive to drug therapy and 11 age-matched nondepressed controls. RESULTS: All patients were clinically depressed and taking antidepressant drugs at the time of the study. The relative blood flow was significantly decreased bilaterally in the frontal cortex, anterior temporal cortex, anterior cingulate gyrus and caudate in the depressed patients compared with the nondepressed healthy controls. The greatest decreases were seen in the paralimbic regions, specifically, the inferior frontal and cingulate cortex. No significant changes were seen in the parietal cortex, occipital cortex or thalami. Psychiatric rating scales correlated poorly with regional blood flow, except for the degree of psychomotor slowing, which was negatively correlated with frontal and cingulate perfusion. CONCLUSION: These findings implicate selective dysfunction of paralimbic brain regions in clinically depressed patients, independent of their medication use, and support the concept of specific neural systems that regulate mood. Recognition of these regional abnormalities may have clinical utility in both the diagnosis and treatment of depression. PMID- 8195878 TI - Prefrontal and temporal blood flow in schizophrenia: resting and activation technetium-99m-HMPAO SPECT patterns in young neuroleptic-naive patients with acute disease. AB - This study assesses prefrontal and temporal regional cerebral blood flow (rCBF) changes in young, neuroleptic-naive schizophrenic patients with acute disease. METHODS: A selected population of 10 young, never-treated schizophrenic women with acute disease was studied by two hexamethylpropyleneamine oxime (HMPAO) brain SPECT sessions, performed 48 hr apart, both at rest and during a prefrontal activation task using the Wisconsin Card Sort Test (WCST). All patients met Diagnostic and Statistical Manual of Mental Disorders, 3rd edition-revised criteria for schizophrenia or schizophreniform disorder, were neuroleptic-naive and had acute symptoms. RESULTS: Under resting conditions, the schizophrenic group had significantly higher rCBF in the prefrontal regions, mainly in the left side and including the anterior cingulate, than did the controls. In addition, schizophrenic patients showed significant interhemispheric differences in prefrontal and posterior temporal index values at rest (left hyperfrontality and left hypotemporality). During WCST activation, the control group showed significant increases in prefrontal blood flow, whereas the schizophrenic group did not. CONCLUSION: These results support a physiologic dysfunction of the prefrontal cortex in schizophrenia that is present at the onset of the illness prior to neuroleptic treatment. Furthermore, both left hyperfrontality and left hypotemporality may indicate a brain lateralization defect in schizophrenia. PMID- 8195880 TI - Predicting outcome in traumatic brain injury: what role for rCBF/SPECT? PMID- 8195879 TI - Prospective evaluation of technetium-99m-HMPAO SPECT in mild and moderate traumatic brain injury. AB - We prospectively evaluated the contribution of 99mTc-HMPAO SPECT in patients who have sustained acute, mild or moderate head trauma. METHODS: Forty-two patients formed the first subgroup of moderate trauma (ModTr) and 25 patients formed the second subgroup of mild trauma (MilTr). All 67 patients underwent an initial SPECT (Tinit) within 4 wk after a closed cranial trauma. After a mean interval of 3 mo from the time of Tinit, all patients were clinically re-evaluated; those with an abnormal Tinit underwent a repeat SPECT (Trpt) as well. All SPECT studies were visually graded by agreement of three observers adjudging a score ranging from 0 (no lesions) to 4. RESULTS: For the group as a whole (ModTr + MilTr), the following results could be derived: (1) in 32/33 Tinit negative cases, clinical symptoms had resolved; (2) the positive predictive value of Tinit was only 20/34 (59%); (3) the sensitivity for the repeat SPECT was 19/20 (95%). CONCLUSION: Our results show that: (1) SPECT alterations correlate well with the severity of the trauma; (2) a negative initial SPECT study is a reliable predictor of a favorable clinical outcome; (3) in cases with a positive initial SPECT, a follow-up consisting of a combination of SPECT and clinical data is necessary; (4) in patients suffering from postconclusive symptoms, SPECT offers an instrument to objective sequelae. PMID- 8195881 TI - Stereotactic PET atlas of the human brain: aid for visual interpretation of functional brain images. AB - In the routine analysis of functional brain images obtained by PET, subjective visual interpretation is often used for anatomic localization. To enhance the accuracy and consistency of the anatomic interpretation, a PET stereotactic atlas and localization approach was designed for functional brain images. METHODS: The PET atlas was constructed from a high-resolution [18F]fluorodeoxyglucose (FDG) image set of a normal volunteer (a 41-yr-old woman). The image set was reoriented stereotactically, according to the intercommissural (anterior and posterior commissures) line and transformed to the standard stereotactic atlas coordinates. Cerebral structures were annotated on the transaxial planes by using a proportional grid system and surface-rendered images. The stereotactic localization technique was applied to image sets from patients with Alzheimer's disease, and areas of functional alteration were localized visually by referring to the PET atlas. RESULTS: Major brain structures were identified on both transaxial planes and surface-rendered images. In the stereotactic system, anatomic correspondence between the PET atlas and stereotactically reoriented individual image sets of patients with Alzheimer's disease facilitated both indirect and direct localization of the cerebral structures. CONCLUSION: Because rapid stereotactic alignment methods for PET images are now available for routine use, the PET atlas will serve as an aid for visual interpretation of functional brain images in the stereotactic system. Widespread application of stereotactic localization may be used in functional brain images, not only in the research setting, but also in routine clinical situations. PMID- 8195882 TI - Input functions for 6-[fluorine-18]fluorodopa quantitation in parkinsonism: comparative studies and clinical correlations. AB - PET has been used to quantify striatal 6-[18F]fluoro-L-dopa (FDOPA) uptake as a measure of presynaptic dopaminergic function. Striatal FDOPA uptake rate constants (Ki) can be calculated using dynamic PET imaging with measurements of the plasma FDOPA input function determined either directly or by several estimation procedures. METHODS: We assessed the comparative clinical utility of these methods by calculating the striato-occipital ratio (SOR) and striatal Ki values in 12 patients with mild to moderate PD and 12 age-matched normal volunteers. The plasma FDOPA time-activity curve (KiFD); the plasma 18F time activity curve (KiP); the occipital time-activity curve (KiOCC); and a simplified population-derived FDOPA input function (KiEFD) were used to calculate striatal Ki. RESULTS: Mean values for all striatal Ki estimates and SOR were significantly lower in the PD group. Although all measured parameters discriminated PD patients from normals, KiFD and KiEFD provided the best between-group separation. KiFD, KiEFD and KiOCC measures correlated significantly with quantitative disease severity ratings, although KiFD predicted quantitative clinical disability most accurately. CONCLUSION: These results suggest that KiFD may be an optimal marker of the parkinsonian disease process. KiEFD may be a useful alternative to KiFD for most clinical research applications. PMID- 8195883 TI - 6-[Fluorine-18]fluorodopamine pharmacokinetics and dosimetry in humans. AB - PET scanning after injection of 6-[18F]fluorodopamine visualizes tissue sympathetic innervation. Organ dosimetric estimates for 6-[18F]fluorodopamine have relied on studies of rats and dogs and on literature about the fate of other radiolabeled catecholamines. This report uses empirical clinical findings in healthy volunteers to refine and extend these estimates. METHODS: Thoracic PET scanning was conducted and arterial blood and urine samples were obtained after intravenous injection of 6-[18F]fluorodopamine into 10 normal volunteers. RESULTS: The main target organs for 6-[18F]fluorodopamine-derived radioactivity were the wall of the urinary bladder (3.3 rem for a 4-mCi dose and 3.31-hr voiding interval) and the kidneys (2.9 rem for a 4-mCi dose) due to urinary excretion of radioactive metabolites of [18F]-6F-DA. The estimates were about one fourth those predicted from studies of laboratory animals. CONCLUSIONS: At administered doses required to visualize the left ventricular myocardium in humans, a 6-[18F]fluorodopamine injection produces acceptable absorbed radiation doses, with the highest doses to the urinary collecting system. PMID- 8195884 TI - Brain tumor imaging with PET and 2-[carbon-11]thymidine. AB - METHODS: To assess the potential of thymidine for imaging brain tumors, 20 patients with untreated (n = 14) and recurrent (n = 6) supratentorial intracranial tumors were studied with PET by using 2-[11C]thymidine (Tdr), and the results were compared with [18F]fluorodeoxyglucose (FDG) PET data. RESULTS: Blood analysis consistently revealed a rapid clearance of the intact Tdr together with the appearance of CO2/HCO3- that, with time, accounted for approximately 70% of the total blood activity. As soon as 10 min after tracer injection, brain images showed a low and homogeneous Tdr distribution over the normal brain structures (cortex-to-blood ratio approximately 1). Visual and quantitative analysis revealed increased Tdr uptake (tumor-to-cortex ratio > or = 1.2) in 11 of 14 untreated tumors and in 5 of 6 recurrent tumors. No correlation was found between Tdr uptake and tumor grade. In 12 of the 14 untreated tumors, FDG uptake was low (tumor-to-cortex ratio: 0.83 +/- 0.79), but a FDG hot spot was visualized in 8 of 10 high-grade and in none of the 4 low-grade tumors. FDG uptake was consistently low in recurrent tumors (tumor-to-cortex ratio: 0.49 +/- 0.19), and PET-FDG was negative in 3 of the 6 cases. CONCLUSION: These data indicate the feasibility of brain tumor imaging with Tdr and suggest the potential clinical usefulness of the method in the detection of tumor recurrences. The specificity of the method remains, however, to be investigated. PMID- 8195885 TI - Computer-assisted evaluation of dipyridamole thallium-201 SPECT in patients with aortic stenosis. AB - Dipyridamole SPECT detects significant coronary artery disease (CAD) in patients without aortic stenosis. This study was done to establish normal 201Tl distribution limits in patients with aortic stenosis and to apply these normal limits to patients with aortic stenosis and angiographically significant CAD (> or = 75% area reduction). METHODS: Fifty-two patients (mean age 68 yr; mean valve area 0.67 cm2) were examined with 201Tl SPECT after dipyridamole infusion (0.56 mg/kg during 4 min). After tomographic reconstruction, basal, mid-ventricular and apical short-axis slices were selected. The highest activity in each six-degree segment was normalized to the maximal activity of each slice. RESULTS: Significant CAD was found in 24 patients. Five patients without CAD, but with localized hypokinesia or left bundle-branch block, were excluded from the reference group which finally consisted of 16 patients. Sensitivity for CAD was 88% when the lowest relative activity in each segment was used as the lower limit of normal. With -2 s.d. and -2.5 s.d. curves the sensitivity was 83% and 75%, respectively. Gender-specific limits were not used. Nonsignificant CAD was found in seven patients (< 75% stenoses). CONCLUSIONS: This study presents the normal distribution of 201Tl uptake for patients with aortic stenosis, using dipyridamole SPECT. The range method had the highest sensitivity for detection of significant CAD. PMID- 8195886 TI - Enhancement of myocardial [fluorine-18]fluorodeoxyglucose uptake by a nicotinic acid derivative. AB - Recently, the euglycemic hyperinsulinemic clamp technique was shown to give excellent image quality during metabolic steady-state conditions. Acipimox is a new potent nicotinic acid derivative that rapidly reduces serum free fatty acid (FFA) levels by inhibiting lipolysis in peripheral tissue. METHODS: To compare the effects of acipimox administration and insulin clamp on [18F]fluorodeoxyglucose ([18F]FDG) uptake and myocardial glucose utilization, five nondiabetic and seven type II diabetic patients who had had previous myocardial infarctions were studied twice: once during a clamp study and once after the administration of acipimox (2 x 250 mg orally). All patients also underwent resting SPECT perfusion imaging prior to PET scans. RESULTS: The patients tolerated acipimox well. Although fasting plasma glucose levels were higher in diabetic patients (9.2 +/- 3.4 versus 5.5 +/- 0.3 mM, p = 0.03), they were decreased both during clamping and after acipimox; during imaging, no significant differences between the groups and approaches were detected. By visual analysis, the image quality and myocardial [18F]FDG uptake patterns were similar during clamping and after acipimox. Compared with the relative [18F]FDG uptake values obtained during clamping, acipimox yielded similar results in normal, mismatch and scar segments (r = 0.88, p = 0.0001). Similar rMGU values were also obtained during both approaches. CONCLUSION: Thus, PET imaging with [18F]FDG after the administration of acipimox is a simple and feasible method for clinical viability studies both in nondiabetic and diabetic patients. It results in excellent image quality and gives rMGU levels similar to the insulin clamp technique. PMID- 8195887 TI - Measurement of global and regional left ventricular function by cardiac PET. AB - To permit assessment by positron tomography of left ventricular mechanical function, methods were developed to measure ejection fraction and regional wall motion and produce realistic images of the beating heart from ECG-gated PET data. METHODS: Following red cell labeling with 15O-carbon monoxide, seven-slice PET data were collected in list mode and reformatted into 16 time frames. Volume rendered cine images were created by the depth-weighted maximum-activity method. To determine the left ventricular ejection fraction, background was subtracted in voxels outside the heart and the cubic datasets were rotated to the angle with the best septal separation. Depth weighting was applied to stimulate a 99mTc study, and the beating images were rendered by summing counts along parallel projection rays. These techniques were validated in 16 patients by comparison with planar studies performed with 99mTc-red cells. RESULTS: Visual grading of regional wall motion yielded exact agreement between the PET and 99mTc methods in 62% of walls with agreement with one grade in 94%. Assessment of quantitative regional wall motion agreed closely with an independent threshold edge detection method. CONCLUSION: PET techniques have been developed to measure left ventricular ejection fraction and regional wall motion and to produce realistic beating images of the cardiac blood pool. This information can be obtained at the same time as measurements of perfusion and metabolism and in the same spatial orientation, thereby permitting quantitative assessment by positron tomography of global and regional mechanical function in relation to flow and metabolism. PMID- 8195888 TI - Canadian midwifery. Travail and triumph. PMID- 8195889 TI - A practical approach to clients who are survivors of childhood sexual abuse. AB - Approximately 30% of all women have experienced some form of sexual abuse in childhood or adolescence. This abuse may result in serious long-term sequelae for the survivor, such as depression, low self-esteem, post-traumatic stress disorder, and addictive behaviors. Nurse-midwives are uniquely equipped to provide health care to survivors of childhood sexual abuse because of their commitment to thorough, sensitive health education. This article draws on current literature and the clinical experience of a nurse-midwife who has cared for many survivors of sexual abuse. It offers suggestions for incorporating identification of survivors into the initial health assessment. Interventions are reviewed including how to approach the physical examination of a survivor and how to provide appropriate care in the intrapartum and postpartum period. Emphasis is given to the development of a referral network. PMID- 8195891 TI - Readership and practice profile of members of the American College of Nurse Midwives. Findings of a direct mail survey. PMID- 8195890 TI - Anticardiolipin antibodies. A review of the literature. AB - Repeated fetal loss may be a result of a variety of causes. Immunological factors have been implicated in fetal loss, intrauterine growth retardation, preeclampsia, and thrombocytopenia. Anticardiolipin antibodies (ACAs) belong to a family of autoantibodies known as antiphospholipid antibodies. Platelet aggregation and increased coagulation results from the presence of these antibodies, and is believed to contribute to the fetal complications. This article is a review of the physiological implications of ACAs, screening criteria for the presence of ACAs, prevalence rates, diagnostic measures, treatment options, and possible postpartum effects of ACAs. When women with recurrent pregnancy losses present for care, the nurse-midwife needs to be able to discuss possible causes, aspects of diagnosis, and treatment options available. With a better understanding of what these are, the nurse-midwife will be better able to plan care that will promote a positive pregnancy outcome. PMID- 8195892 TI - Entrepreneurship. The realities of today. AB - Entrepreneurship is a new and developing area for nurse practitioners. This article is a descriptive study of an entrepreneur practice, established by a certified nurse-midwife. Interviews were conducted to determine issues germane to this practice. Third-party reimbursement was identified as a crucial issue. A list of suggested readings related to the issues of entrepreneurships and third party reimbursement for nurse practitioners is presented. PMID- 8195893 TI - Critical thinking and the nurse-midwifery management process. AB - Within recent years, the general educational arena has placed a greater emphasis on the incorporation of critical thinking within student curricula. Critical thinking as a learning tool teaches students the art of reason and logic, and encourages the preparation for dynamic situations that occur outside the classroom. The authors believe that critical thinking and nurse-midwifery are inherently intertwined. To utilize the nurse-midwifery management process in the provision of sound and safe practice, the nurse-midwife must also be a critical thinker. The management process of data gathering, assessment, diagnosis, planning, implementation, and evaluation parallels the domains of the critical thinker's process: intellectual standards, modes of reasoning, traits of mind, reasoning abilities, and elements of thought. This article presents similarities between the two models. PMID- 8195894 TI - Sensitivity, specificity, and predictive value. Concepts for clinicians. PMID- 8195895 TI - Time associated with components of clinical services rendered by nurse-midwives. Sample data from phase II of nurse-midwifery care to vulnerable populations in the United States. AB - The purpose of this article is to present prospective data from phase II of "Nurse-Midwifery Care to Vulnerable Populations in the United States" about the components of clinical services provided to women and infants by CNMs, and the amount of time spent providing services in a variety of settings. Three hundred sixty nine CNMs collected data on 16,729 client visits. The results indicate that the amount of time taken by a CNM to conduct an ambulatory client visit is similar, regardless of site. There were slight differences in the length of time taken for major components of a visit between sites but, in general, there was a remarkable similarity. The amounts of time spent in intrapartum care and inpatient visits is also reviewed. PMID- 8195896 TI - Central importance of evidence for validity and reliability in clinical research studies. PMID- 8195897 TI - Why do some people develop two or more inflammatory conditions (ie, carpal tunnel syndrome, Dupuytren's contracture, trigger finger, etc) without any clear-cut etiologic factor(s) being present? PMID- 8195898 TI - What are the health risks of employees with a history of asthma when placed as handlers in an animal research facility? PMID- 8195899 TI - Detection of activated ras p21 in urine samples associated with bladder and prostate cancer. PMID- 8195900 TI - Biological monitoring of exposure to polycyclic aromatic hydrocarbon in an electrode paste plant. AB - We have compared several biomarkers for polycyclic aromatic hydrocarbon (PAH) exposure among electrode paste plant workers and workers not occupationally exposed to PAH. The PAH exposure was quantitated from samples collected with person-attached sampling devices. The mean particulate PAH exposure level in the plant was 14.4 micrograms/m3. The level of pyrene was significantly correlated with both PAH level and the level of selected carcinogenic PAHs in this type of exposure. The mean concentration of the biomarker 1-hydroxypyrene in the PAH exposed workers' urine was 6.98 mumol of 1-hydroxypyrene per mole of creatinine compared with 0.08 and 0.14 mumol of 1-hydroxypyrene per mole of creatinine in the two reference groups. PAH-DNA adducts were measured in DNA from white blood cells by the ultrasensitive enzyme radioimmunoassay (USERIA) and the 32P postlabeling technique. Only urinary 1-hydroxypyrene was significantly increased in the PAH-exposed group. PMID- 8195901 TI - Laboratory work and pregnancy outcome. AB - Spontaneous abortions among women working in laboratories, and congenital malformations and birth weights of the children were examined in a retrospective case-referent study. In the spontaneous abortion study there were 535 women (206 cases and 329 referents), and in the malformation study 141 women (36 cases and 105 referents). The analysis of the birth weights concerned 500 women (referents). Significant associations with spontaneous abortion were found for exposure to toluene (odds ratio [OR], 4.7, 95% confidence interval [CI], 1.4 to 15.9), xylene (OR 3.1, CI 1.3 to 7.5) and formalin (OR 3.5, CI 1.1 to 11.2) > or = 3 days a week, adjusted for the covariates. Most of the women exposed to formalin and xylene were working in pathology or histology laboratories. No association with congenital malformation was found. PMID- 8195902 TI - Occupationally acquired tuberculosis: what's known. AB - Tuberculosis (TB) morbidity and mortality have increased substantially since the mid-1980s in areas with a high prevalence of medically underserved populations, human immunodeficiency virus, foreign-born persons, residents of long-term care facilities and crowded correctional institutions, and alcoholics and intravenous drug abusers. The occupational risk has likewise increased for those exposed to these high-risk people in the course of their work. The magnitude of the occupational hazard is present unclear, although implications are disturbing. We used available data bases containing occupational exposure information, and telephone surveys, in an attempt to elucidate the magnitude of risk of occupationally acquired TB. We obtained up-to-date employee conversion rates at high-risk institutions, identified changing rates of TB infection and disease over time, documented high conversion rates following accidental exposures, and revealed a relative lack of reported TB disease and deaths. Numerous barriers to worker protection against TB are identified and recommendations are made to reduce the risk of occupationally acquired tuberculosis. PMID- 8195903 TI - Measuring second-order selection bias in a work site health program. AB - Magnitude and direction of second-order self-selection bias were assessed in a sample of 93,807 IBM employees who participated in the company's Voluntary Health Assessment (VHA) Program, by comparing repeat participants with one-time participants and by simulating selection into the repeat sample. One-time and repeat VHA participants differed systematically but not uniformly in several health characteristics. Repeat participants improved significantly in risk relevant behaviors and health risk measures. Simulation of selection bias by excluding healthier or less healthy participants from the repeat VHA sample showed findings of gain to be robust. In studies of gain, second-order selection bias cannot automatically be assumed to inflate gain nor to be of sufficient magnitude to affect conclusions about program effects. Simulation is a useful tool for gauging direction and magnitude of selection bias. PMID- 8195904 TI - Baldrige value to occupational health services. AB - Applying the criteria of the Malcolm Baldrige National Quality Award should help guide the implementation of total quality management, or continuous quality improvement, within occupational and environmental health organizations. Based upon the prior elucidation of necessary parameters to achieve this goal, the Baldrige criteria framework is found to encompass these components in an integrated way and to provide a rigorous method of assessment. Also, its guidelines provide a number of other unique advantages for occupational physician managers whose aim is quality excellence and future competitiveness. PMID- 8195905 TI - Physical work load and its assessment among the nursing staff in nursing homes. AB - A study was conducted to investigate the physical work load and the prevalence of musculoskeletal complaints of nurses in nursing homes. Thirty-six female subjects selected from three nursing homes in the Netherlands participated in an observational study. In addition, the total nursing staff (n = 668) was invited to take part in a questionnaire survey (response was 94%). It was noticed that almost 60% of the observed time was spent on nonpatient-related activities. Moreover, activities alternated rapidly and seldom lasted longer than 4 minutes on average. Twenty percent of the observed time was spent in "poor" work postures as defined by the Ovako Working Posture Analyzing System (Action Category 2 to 4). Activities contributing most to these poor work postures were patient care and household and preliminary tasks. Perceived exertion as scored on the Borg CR10 scale was highest during patient-related activities. This holds also for a relative increase of heart rate. Questionnaire results showed prevalences of 41%, 35%, and 20% respectively, for back, arm/neck, and leg complaints. From this study it can be concluded that not only patient-related activities should be taken into consideration for the improvement of work postures and other potential strenuous aspects of nursing work. Household and preliminary tasks, ergonomic layout of the ward, and work pressure also deserve attention. PMID- 8195906 TI - Small, blue collar work site hypertension screening: a cost-effectiveness study. AB - This study determined the cost-effectiveness of one- versus two-stage hypertension screening at small to medium-sized blue collar, multicultural work sites using voluntary health organization and public health unit personnel. Workers with diastolic blood pressure (DBP) > or = 90 mm Hg were randomly allocated to one- or two-stage screening with differing physician referral protocols based on blood pressure level and treatment status. At first screening of 7856 workers, 12.5% had DBP > or = 90 mm Hg or < 90 and on medication with 64% aware of having hypertension, 42% on medication and 30% controlled (DBP < 90 mm Hg). One year later, there were no significant differences in effects or cost effectiveness between groups. Both had significant DBP decrease (8.5 mm Hg), 54% had seen a physician within the recommended time, and 50% were controlled on medication or any treatment. One-stage screening, being easier to implement, is the preferred option. PMID- 8195907 TI - Surveillance of construction worker injuries through an urban emergency department. AB - To learn more about the causes of nonfatal construction worker injuries, and to identify injury cases for further work-site investigations or prevention programs, an emergency department-based surveillance program was established. Construction workers with work-related injuries or illnesses were identified by reviewing the medical records of all patients treated at the George Washington University Emergency Department between November 1, 1990 and November 31, 1992. Information regarding the worker, the injury, and the injury circumstances were abstracted from medical records. Information was obtained on 592 injured construction workers from numerous trades. Lacerations were the most commonly treated injuries among these workers, followed by strains and sprains, contusions, and eye injuries. Injuries were most commonly caused by sharp objects (n = 155, 26%), falls (n = 106, 18%), and falling objects (n = 70, 12%). Thirty five percent of injuries were to the hands, wrists, or fingers. Among the twenty eight injuries severe enough to require hospital admission, eighteen (64%) were caused by falls. Laborers and Hispanic workers were overrepresented among these severe cases. Emergency Department records were a useful surveillance tool for the initial identification and description of work-related injuries. Although E codes were not that useful for formulating prevention strategies, detailed review of injury circumstances from Emergency Department records was valuable and has helped to establish priorities for prevention activities. PMID- 8195908 TI - The effect of a materials-based intervention on knowledge of risk-based clinical prevention screening guidelines. AB - The release of the U.S. Preventive Services Task Force guidelines (GUIDELINES) introduces an opportunity to modify patient expectations about the timing of routine examinations. This randomized, controlled study examines the effect of a materials-based educational intervention on knowledge and beliefs about risk based preventive screening guidelines. The study was conducted in a large multi specialty group practice participating in a network model HMO in the upper midwest with over 250,000 members. Subjects were selected from patients of a primary care clinic in a suburban section of a major metropolitan area. A 48-page prevention guidebook based on the GUIDELINES was distributed to a randomly assigned treatment group of 200 patients enrolled in an HMO. A 22-item questionnaire on preventive health services that measured respondents' age adjusted risks and knowledge of risk-based screening guidelines was sent to both experimental and control groups. A 69% response rate was achieved. chi 2 analysis and t-tests showed that the treatment group was significantly more accurate in identifying recommended GUIDELINES for colon examinations (digital rectal, stool occult, sigmoidoscopy), blood pressure, and Pap tests. No significant differences related to identifying GUIDELINES for mammograms and clinical breast examinations were found between the groups. Communications about new screening guidelines can yield positive but selective changes in knowledge and beliefs about appropriate screening intervals. PMID- 8195910 TI - Outcomes of treatment of socially rehabilitated methadone maintenance patients in physicians' offices (medical maintenance): follow-up at three and a half to nine and a fourth years. AB - OBJECTIVE: To determine whether selected socially rehabilitated former heroin addicts maintained on methadone can continue successful rehabilitation while maintained on methadone by primary care physicians rather than licensed clinics. This procedure has been termed "medical maintenance." DESIGN: Cohort study with 42-111 months of follow-up. SETTING: Offices of hospital staff physicians (internists or family practitioners). PATIENTS: The 100 patients met extensive entry criteria, including five or more years in conventional methadone maintenance treatment; stable employment or other productive activity; verifiable financial support; and no criminal involvement, use of illegal drugs, or excessive alcohol use within three or more years. MEASUREMENTS AND MAIN RESULTS: Outcome measures used were retention in treatment, discharge for one of several reasons, lost medication incidents, and substance abuse. At one, two, and three years of treatment, 98, 95, and 85 patients, respectively, remained in medical maintenance. Cumulative proportional survival in treatment was 0.735 +/- 0.048 at five years and 0.562 +/- 0.084 at nine years. After 42-111 months, 72 patients remained in good standing; 15 patients had unfavorable discharges (11 for cocaine use, three for misuse of medication, and one for administrative violations); seven voluntarily withdrew from methadone in good standing (after receiving it for 9.1-24.4 years); four died; one transferred to a chronic care facility; and one voluntarily left the program. CONCLUSIONS: Carefully selected methadone maintenance patients in medical maintenance have a high retention rate and a low incidence of substance abuse and lost medication. Voluntary withdrawal from methadone maintenance after one or two decades is possible. The authors believe that medical maintenance should be made available to appropriate patients in other localities. PMID- 8195909 TI - The impact of socioeconomic status on the intensity of ambulatory treatment and health outcomes after hospital discharge for adults with asthma. AB - OBJECTIVES: To examine whether differences in intensities of care by socioeconomic status and race result in worse health among adults with asthma post-hospital discharge. DESIGN: Patients were enrolled during hospitalization and recontacted three months after discharge. PATIENTS: Those aged 18-55 years, with a primary diagnosis of asthma (n = 97). MAIN OUTCOME MEASURES: Regular source of care, "intensive" therapy (use of an anti-inflammatory agent, pulmonary function testing, or an asthma specialist), and patient-reported (Intermediate Activities of Daily Living Scale [IADL] score, dyspnea) and performance-based (peak flow rate) measures of health status post-discharge. RESULTS: 28% of patients with a yearly income less than $16,000 had no regular source of care, compared with 11% of those with an income from $16,000 to $29,999 and no patient with an income of at least $30,000 (p = 0.003). Similarly, intensive therapy was received by 40%, 67%, and 81% of these groups (p = 0.005). Education had similar associations. Patients with no regular source of care or who did not receive intensive therapy had significantly worse health. Patients of lower socioeconomic status had health outcomes that were up to 25% lower than those of patients of higher socioeconomic status (p < 0.05 for differences in LADL score, dyspnea, and peak flow by educational levels and for differences in dyspnea by income levels), after adjustment for age, gender, race, insurance status, and baseline health. After further adjustment for source of care and intensity of therapy, differences in health outcomes by socioeconomic status uniformly decreased in magnitude and only the differences in LADL scores and dyspnea by educational levels remained statistically significant. Although nonwhite patients were less likely to have a regular source of care or to receive intensive therapy, there was no difference in health outcomes by race. CONCLUSIONS: Patients of lower socioeconomic status who have asthma have worse health outcomes post-hospital discharge, which appear to be due in part to less continuous and less intensive treatment. PMID- 8195911 TI - A computerized intervention to improve timing of outpatient follow-up: a multicenter randomized trial in patients treated with warfarin. National Consortium of Anticoagulation Clinics. AB - OBJECTIVE: To evaluate a computerized scheduling model that employs nonlinear optimization to recommend optimal follow-up intervals for patients taking warfarin. DESIGN: Randomized trial. SETTING: 5 anticoagulation clinics. PATIENTS/PARTICIPANTS: 620 patients expected to receive warfarin for > or = 6 weeks. INTERVENTIONS: Computer-generated recommendations for scheduling the next visit were presented to or withheld from practitioners. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were the follow-up interval scheduled by the provider, the interval at which the patient actually returned to clinic, and the quality of anticoagulation control (computed as the absolute difference between the measured and target prothrombin times [PTRs] or international normalized ratios [INRs]). Follow-up intervals scheduled for the patients whose practitioners received computer-generated recommendations were significantly longer than those for control patients (mean, 4.4 vs 3.5 weeks, p < 0.001), despite the fact that the practitioners modified the suggested return interval by > 1 week on 40% of the visits. The interval at which the intervention group actually returned to clinic was also longer (mean, 4.4 vs 4.1 weeks, p < 0.05), even though the control patients tended to return at longer intervals than were scheduled by their practitioners. Control of anticoagulation was nearly the same among experimental and control patients. Life-threatening complications occurred in the care of three experimental patients and one control patient, while other serious complications occurred in the care of 16 experimental patients and 17 control patients. CONCLUSIONS: Recommendations based on nonlinear optimization prompted clinicians to schedule less frequent follow-up for patients taking warfarin, with no deterioration in anticoagulation control. This approach to scheduling can potentially reduce utilization while maintaining quality of care for patients who require long-term monitoring. PMID- 8195912 TI - Do ratings on the American Board of Internal Medicine Resident Evaluation Form detect differences in clinical competence? AB - OBJECTIVE: To determine whether raters using the American Board of Internal Medicine (ABIM) Resident Evaluation Form can detect differences among residents in clinical competence. DESIGN: Cross-sectional study. SETTING: Inpatient general medicine service in a university-affiliated public hospital. PARTICIPANTS: University-based internal medicine (UCIM) residents (ABIM certifying examination pass rate, 91%; mean score, 95th percentile), community hospital-based internal medicine (CHIM) residents (ABIM examination pass rate, 68%; mean score, 42nd percentile), and residents from three university-based non-internal medicine (UC non-IM) programs all assigned to the same inpatient general medicine service over a three-year period. Four hundred eighty-nine evaluations of 110 postgraduate year-one residents were analyzed. MEASUREMENTS AND MAIN RESULTS: Mean ratings for the UCIM residents were significantly higher than those for the CHIM or UC non-IM residents (analysis of variance [ANOVA], p < 0.05). Variance was smallest for the UCIM residents (F test, p < 0.01), and only the UCIM residents' mean scores were in the "superior" range (7-9) in all evaluated categories. The mean ratings for the CHIM residents while at the university-affiliated hospital were not significantly different from the ratings of the same residents at their home hospital. The ratings for the CHIM residents at either site were significantly lower than those for the UCIM residents in all categories (ANOVA, p < 0.05). Factor analysis revealed a single factor accounting for 76% of the variance among the ratings with all dimensions loading high on that factor (0.75-0.95), providing evidence for a "halo" effect. Mean interrater agreement over all variables was 0.87, indicating good consistency among raters. CONCLUSIONS: Ratings on the ABIM Resident Evaluation Form detect global differences among residents in clinical competence in the expected direction based on type of training program and performance on the ABIM certification examination, but fail to differentiate among the nine evaluated dimensions of clinical care. This rating method may be valid for assessing overall clinical performance, but is less useful for providing feedback in specific areas to individual residents. PMID- 8195913 TI - The feasibility and value of using patient satisfaction ratings to evaluate internal medicine residents. AB - OBJECTIVE: To determine the feasibility and value of using patient satisfaction ratings to evaluate the physician-patient relationship skills of medical residents. DESIGN: A cross-sectional survey was used to collect patient satisfaction information for medical residents from all patients attending the out-patient teaching clinics over a three-month period. The feasibility of patient rating was assessed by evaluating the reliability of resident satisfaction scores and potential sources of bias in rating. The value of using this method was assessed by evaluating the proportion of variance in ratings attributable to residents, the prevalence of residents with ratings substantially below average, and the effect of training on patient satisfaction. SETTING: The medical clinics of two teaching hospitals at McGill University. PARTICIPANTS: 91 medical residents and clinical clerks, 1,003 patients, and 1,219 visit ratings. RESULTS: An average of 12.2 satisfaction ratings were collected per resident, providing a reliability of 0.56 (intraclass correlation) for resident satisfaction score. Adjustment for differences in patient populations would be necessary to obtain comparable scores among residents. Fifteen percent of the residents had a substantially greater proportion of poor and fair satisfaction ratings than the study average. Residents were responsible for a substantial proportion of the variance in clinic waiting time and patient satisfaction rating. Training appeared to have no effect on improving satisfaction scores, except among women residents. CONCLUSIONS: Patient satisfaction ratings provide valuable information about a resident's ability to establish an effective physician-patient relationship. However, the number of ratings required to obtain a reliable estimate of resident skill may limit the feasibility of using patient ratings as part of residency evaluation. PMID- 8195914 TI - Communication barriers between attending physicians and residents. PMID- 8195915 TI - Prescription drug costs as a reason for changing physicians. AB - The authors conducted a telephone survey of 200 patients who had recently transferred their health care to a Veterans Affairs (VA) medical center. Of the study patients, 56% considered prescription drug costs to be the main reason or a major contributing reason for transfer (95% confidence interval 49% to 63%). The mean out-of-pocket prescription drug cost for these patients was $139 per month, compared with $47 per month for patients for whom drug costs were a minor reason or not a reason at all (p < 0.001). Drug costs are a principal reason for patients to transfer their health care to the VA. PMID- 8195916 TI - The geriatric medication algorithm: a pilot study. AB - A geriatric medication algorithm designed to reduce inappropriate prescribing was tested in a resident outpatient clinic. The medications of patients over 65 years old taking more than three medications (n = 41) were compared pre- and post algorithm using the paired t-test. Pre-algorithm, the average number of drugs was 5.8 per patient (SD 1.62). Fifteen medications (6.4%) were discontinued, seven were substituted for a less toxic medication, and five were added. Post algorithm, the average number of drugs was 5.6 (SD 1.69), mean difference 0.3 (SD 0.67), p < 0.025. Drugs discontinued were more likely to be high risk compared with drugs used at baseline; drugs added were less likely to be high risk. In this pilot study, the authors conclude that the algorithm helps resident physicians reduce inappropriate prescribing. PMID- 8195917 TI - Methods of preparing for the Certifying Examination in internal medicine and their efficacy. AB - Candidates for the 1991 Certifying Examination were asked how they prepared for the examination. There were 2,780 respondents (32% of the eligible candidates). The responding candidates used a mean of 5.2 study methods and gave higher educational value ratings to methods used most frequently. Regression analyses showed no independent contribution of study method or effort to explaining the variance in score for first-time takers, and a 2% contribution for repeat takers. Program director ratings were the most important predictors of score for first time takers and previous examination score for repeat takers. Intensive study is likely to produce at most a small improvement in performance. PMID- 8195919 TI - Asthma, socioeconomic status, and health care reform. PMID- 8195920 TI - Still an awesome duty. PMID- 8195918 TI - Futile medical treatment: a review of the ethical arguments and legal holdings. PMID- 8195921 TI - Alzheimer's disease: pathophysiology and the hope for therapy. AB - The approximately 4.5 million Alzheimer's disease victims in the United States represent a major public health problem resulting in annual expense topping $100 billion, with the Oklahoma share being about $500 million. This problem will be even larger as the baby boomer generation reaches the ages of maximum prevalence of Alzheimer's disease. Research has provided only meager insights into this devastating disease, but has permitted some rational hypotheses concerning potential treatment. Still, the definitive diagnosis of Alzheimer's disease requires pathologic confirmation. In interviews with families following the autopsy, it is apparent that the disease is poorly understood by both the family members and many of the health care workers with which they have dealt. Thus, this review (based upon the questions raised by families and their physicians) examines the currently understood mechanisms and pathogenesis of Alzheimer's disease, the hereditary patterns, and the hope for therapy. PMID- 8195922 TI - Farm-related injury fatalities in Oklahoma, 1987-1991. AB - Farm-related injury is often cited as a major factor in rural health care. This is an attempt to obtain an estimate of the frequency of serious farm injuries in Oklahoma. It is apparent that current available data bases are not adequate to be definitive, but mortality data is available, albeit incomplete. One hundred thirty-two deaths were recorded on death certificates for 1987 through 1991, with falls accounting for nearly half. The other data are summarized, and a review of the farm injury literature is presented. In summary, it is clear that farm injuries are a significant problem and steps to prevent them are required. PMID- 8195923 TI - Upper gastrointestinal endoscopy: its clinical use and safety at a transplant center. AB - Upper gastrointestinal endoscopy is a widely practiced clinical procedure that has become routine in even the most remote medical environments. Its application at a liver transplant center represents the use of this particular technology at the opposite extreme of medical practice and its use in a unique and severely ill group of patients. The following is a description of the author's experience with upper gastrointestinal endoscopy at the University of Pittsburgh's liver transplant center. Despite the severity of illness of the patients seen at this center, documented by the high frequency of patients seen with abnormal prothrombin times and low platelet counts, upper gastrointestinal endoscopy performed either for diagnostic or therapeutic procedures has been found to be safe. The disease processes that affect transplant patients both before and after transplantation are not seen frequently in the general practice of gastroenterology. Thus the endoscopist at a transplant center has to be able to recognize, identify, and treat the unique problems seen in a transplant population. PMID- 8195924 TI - Infant mortality in Oklahoma, 1970-1990. AB - Patterns of infant mortality in Oklahoma are unlike the rest of the United States. Oklahoma has a significantly higher post neonatal mortality rate than the United States, with SIDS and congenital disorders being the leading causes of death in that age group. Conversely, Oklahoma has a significantly lower neonatal mortality rate than the United States. Vital statistics information for the period 1970-1990 are examined to describe patterns of infant death in Oklahoma. Despite long-term decreasing trends in infant death, disconcerting trends were observed in 1990 suggesting that a stronger infant mortality reduction strategy is needed in Oklahoma. Potential areas for public health intervention are suggested based on Oklahoma-specific data. PMID- 8195925 TI - Deaths, suffering, and costs. PMID- 8195926 TI - Tumour-associated leucocytes: friends or foes in breast carcinoma. PMID- 8195927 TI - Cell cycle-related variation and tissue-restricted expression of human cyclin D1 protein. AB - Recent evidence from genetic studies suggests that abnormalities of some of the members of the cyclin superfamily may be intimately associated with tumourigenesis, most likely through deregulation of the cell cycle control. In an attempt to elucidate the potential role of cyclin D1 (a gene located within the 11q13 amplicon and a candidate BCL-1, PRAD-1 oncogene) in the pathogenesis of human neoplasias, we have developed and characterized a novel monoclonal antibody specifically recognizing cyclin D1 protein in various assays including immunohistochemistry on frozen and paraffin sections. Using the DCS-6 antibody as a tool, we now show a characteristic cell cycle-dependent variation of the cyclin D1 protein in human cultured cells and report on the first immunohistochemical study of this G1 cyclin in a range of normal human tissues and breast carcinomas. Analysis of normal tissues revealed generally low levels of cyclin D1 protein, mainly restricted to the proliferative zones of some epithelial tissues, and the lack of its expression in several human tissues including lymph nodes, spleen, and tonsils. In contrast, pronounced overexpression/nuclear accumulation of cyclin D1 was found in 37 per cent of cases in a series of 35 primary ductal carcinomas of the breast. We conclude that the DCS-6 antibody provides a potentially useful tool for the establishment of simple methods suitable for verifying any diagnostic and/or prognostic value of this novel marker on large series of histological specimens and opens the way for biochemical, immunocytochemical, and immunohistochemical studies of the role played by cyclin D1 aberrations in human oncogenesis. PMID- 8195928 TI - Expression of the ret proto-oncogene product in human normal and neoplastic tissues of neural crest origin. AB - The histological localization of the ret proto-oncogene (proto-ret) product was examined in neural crest-derived and neuronal tissues together with their neoplastic counterparts by immunohistochemistry using a polyclonal antibody. Schwann cells, neurons, sympathetic ganglia, and cells of the adrenal medulla were positive for the proto-ret product, whereas melanocytes were negative. Positive results were obtained from neural crest-derived tumours such as schwannoma (69 per cent, 11/16), neurofibroma (59 per cent, 13/22), neuroblastoma (80 per cent, 4/5), phaeochromocytoma (100 per cent, 3/3) and medullary thyroid carcinoma (100 per cent, 3/3). The antibody reacted with all of the 22 astrocytomas examined. With negative proto-ret expression in melanocytic tumours, proto-ret expression was considered to correlate with the differentiation of some lineages of neural crest-derived cells. PMID- 8195929 TI - Nm23 'anti-metastatic' gene product expression in colorectal carcinoma. AB - Nm23 is a putative metastasis suppressor gene and alterations in this gene have been reported in colorectal carcinomas suggestive of a role for nm23 in the dissemination of these tumours. In this study we used an affinity purified polyclonal antibody, ab-11, on formalin-fixed, paraffin-embedded sections of colorectal carcinomas from 46 patients in a three-stage avidin-biotin complex immunoperoxidase technique. Follow-up of these patients was until time of death or for 5 years, with a mean time of 31.2 months. Two observers scored the staining results from 1 to 3 according to the proportion of tumour cells positive. The association of nm23 staining with survival, sex, age, vascular invasion, and Dukes' stage was determined using Cox's regression model. The association of death from colorectal cancer and nm23 status reached marginal significance in this study (P = 0.0417). Moreover, there is some suggestion of a protective effect from nm23 as the relative risk of dying from colorectal cancer for each increment of nm23 positivity is 0.573 (95 per cent confidence limits 0.34-0.98). PMID- 8195930 TI - Retinoblastoma and p53 tumour suppressor gene protein expression in carcinomas of the thyroid gland. AB - One hundred and thirty-one thyroid tumours were examined immunohistochemically for expression of retinoblastoma (RB) and p53 protein. The results demonstrate that RB protein is not lost in any cases, indicating that inactivation of the RB gene is unlikely to play a central role in the pathogenesis of thyroid tumours. Eighteen of 24 (75 per cent) undifferentiated carcinomas, 6 of 32 (19 per cent) papillary carcinomas, 5 of 29 (17 per cent) follicular carcinomas, and 6 of 46 (13 per cent) medullary carcinomas showed p53 protein nuclear staining. In 46 per cent of the undifferentiated carcinomas many of the tumour cells had accumulated p53 protein, whereas in the other positive cases less than 5 per cent of the cells had increased p53 protein levels. Our results strongly suggest that p53 protein abnormalities play a crucial role in the progression of well differentiated to undifferentiated thyroid carcinomas. PMID- 8195931 TI - Expression of bcl-2 gene product in neuroblastoma. AB - The expression of bcl-2 is associated with inhibition of apoptosis and prolonged cell survival. The purpose of this study was to examine the immunoreactivity of neuroblastoma and ganglioneuroblastoma tissue samples to the bcl-2 gene product in order to see if it was related to prognosis. BCL-2 protein was detected in all the 46 formalin-fixed, paraffin-embedded samples from 34 patients representing all clinical stages and sites of involvement. Immunopositivity was observed in tumours from the primary and metastatic sites. Moreover, it was demonstrated in the pre-chemotherapy and the post-chemotherapy samples from six cases with stage 4 disease. It was observed in neuroblasts in various stages of differentiation. A small proportion of undifferentiated neuroblasts were negative. As BCL-2 oncoprotein was present in all the cases irrespective of the clinical outcome, it does not appear to be one of the factors influencing prognosis. PMID- 8195932 TI - Ulcer-associated cell lineage. PMID- 8195933 TI - Expression of p53 protein in nasopharyngeal carcinoma. PMID- 8195934 TI - Schistosoma haematobium cercarial host-finding and host-recognition differs from that of S. mansoni. AB - Schistosoma haematobium cercarial host-finding responses differ from those of Schistosoma mansoni. The attachment response to warm substrata is more sensitive and intense and is inhibited by unphysiologically warm substrata. Attachment is also stimulated by L-arginine as the exclusive chemical cue of the human skin surface (threshold 3 microM); however, the response is drastically lower than that of S. mansoni cercariae. No chemical host stimulus could be identified for an enduring contact with the host after attachment. After attachment, the cercariae creep in a temperature gradient toward heat source; their response is, however, more sensitive than that of S. mansoni (threshold 0.03 vs. 0.15 C/mm). Creeping S. haematobium cercariae orientate in chemical gradients in the same way as S. mansoni cercariae toward L-arginine as the exclusive chemical signal of the human skin surface. The selective benefit of this behavior is not yet understood. The penetration of both species is stimulated by free fatty acids from the human skin surface, not by heat. Thus, S. haematobium responds more to thermal host signals, whereas S. mansoni prefers chemical host signals. PMID- 8195935 TI - Lead accumulation in Pomphorhynchus laevis and its host. AB - Adults of Pomphorhynchus laevis were collected from the intestines of 10 chubs (Leuciscus cephalus) from the river Ruhr near Bochum, Germany. The acanthocephalans and various tissues of the fish (muscle, liver, and intestine) were analyzed for lead with electrothermal atomic absorption spectrometry. The mean lead level in the parasite was 54 micrograms/g wet weight, which was 284 times more than in the host intestine, 771 times more than in host liver, and 2,700 times more than in host muscle. Thus, P. laevis may serve as a very sensitive bioindicator for the presence of biologically available lead in aquatic ecosystems. PMID- 8195936 TI - Contractile characteristics of the flexor muscle of mice infected with Trichinella spiralis, T. nativa or T. pseudospiralis. AB - A comparative analysis of skeletal muscle isometric contractile characteristics was performed in vivo on the flexor muscle of mice infected 6 mo earlier with 400 larvae of Trichinella pseudospiralis, Trichinella spiralis, or Trichinella nativa. The control group consisted of age- and sex-matched uninfected mice. The mice were injected with 0.1 ml of 50% urethane in saline, and the skin of the left hind limb was cut open longitudinally. The exposed flexor muscle was freed from the adjacent tissue and left attached freely to the knee joint while the tendon was hooked to a transducer. The signals were amplified with an amplifier connected to a chart recorder. The sciatic nerve was exposed and attached to an electrode. Impulses were generated and muscle contraction recorded. The exposed muscle and nerve were bathed in normal Krebs solution at all times and the animals were kept alive during the experiment. The normal muscle twitch tension of uninfected mice reached an average of 2.26 +/- 0.24 (SD) g. Tetany was achieved at 15 Hz. Low-Ca2+ Krebs depressed the twitch tension to 2.0 +/- 0.08 g while tetany remained at 15 Hz. Muscle twitch tension in mice infected with T. pseudospiralis reached 2.47 +/- 0.17 g and tetany at 15 Hz. Low Ca2+ depressed twitch tension to 1.14 +/- 0.12 g. Tetany was achieved at 20 Hz. In contrast, the muscle twitch of mice infected with T. nativa was significantly reduced to 1.4 +/ 0.09 g and tetany at 15 Hz. Low Ca2+ depressed twitch tension to 0.9 +/- 0.16 g and tetany at 15 Hz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195937 TI - In vitro uptake and incorporation of [3H]glucosamine and [3H]leucine by Plagiorchis elegans metacercariae. AB - We examined the ability of Plagiorchis elegans metacercariae to take up [3H]glucosamine and [3H]leucine in vitro and incorporate these precursors into parasite tissues at various times in their development. Uptake of both precursors was greater by young metacercariae (< or = 8 hr postinfection [PI]) than old metacercariae (> 8 hr PI). Virtually all [3H]glucosamine was incorporated into juvenile worms, whereas only small amounts of [3H]leucine were incorporated into both juvenile worms and cyst walls. [3H]glucosamine was incorporated into a variety of proteins by 2-hr- and 5-day-old metacercariae as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography. There was evidence of developmentally regulated or stage-specific expression of 14-, 19.5-, and 37-kDa proteins by older metacercariae. These results suggest a differential incorporation of nutrients procured from the insect host into parasite tissues by metacercariae of different ages over the course of their development. PMID- 8195938 TI - Correlation of phosphoinositide hydrolysis with exflagellation in the malaria microgametocyte. AB - Cellular responses to growth factors, hormones, and other agonists have been shown in many animal cell systems to be mediated by the signal transduction cascade controlled by phospholipase C. One such response, calcium mobilization, is regulated by the concerted effect of several specific inositol (poly)phosphates. Another response, protein phosphorylation, is regulated by other phospholipase C (PLC) hydrolysis products. Mature gametocytes are specialized cells primed for transformation into gametes immediately upon removal from the vertebrate bloodstream, thereby initiating the sexual cycle in a vector mosquito. This study showed that PLC hydrolysis products, inositol (1,4,5)triphosphate and diacylglycerol, are correlated with the initial events of flagellar development; they are implicated in synchronizing this crucial transformation for the parasite and hence the continued transmission of the parasite, which leads to this debilitating disease. PMID- 8195939 TI - Evaluation of different medium supplements for in vitro cultivation of Brugia malayi third-stage larvae. AB - Growth and development of Brugia malayi (Nematoda: Filarioidea) third-stage larvae (L3) were compared in 5 medium supplements. The basic culture medium (NI) consisted of a 1:1 (v/v) mixture of NCTC-135 and Iscove's modified Dulbecco's medium, an antibiotic/antimycotic mixture, and 1 of the following 5 supplements: 25 mg/ml bovine albumin fraction-V (BAF), 10% fetal bovine serum (FBS), 10% commercially obtained human serum (CHS), 10-15% pooled human serum from hospital patients (PHS), and 10-15% human serum from a single individual (SHS). Cultures were maintained at 37 C in an atmosphere of 5% CO2 in air. NI-BAF and NI-CHS did not support molting of L3 to fourth-stage larvae (L4), whereas NI-FBS, NI-PHS, and NI-SHS did support molting of L3 to L4 but only the larvae in NI-SHS attempted the fourth molt. Growth and development of in vitro larvae in NI-PHS and NI-SHS were comparable to that observed in jirds for the first 28 days, after which the in vitro larvae lagged behind in vivo larvae. Optimal growth and development may be dependent on certain as yet unidentified components of specific human serum. PMID- 8195940 TI - In vitro cultivation of exoerythrocytic stages of the simian malaria parasites Plasmodium fieldi and Plasmodium simiovale in rhesus monkey hepatocytes. AB - Exoerythrocytic stage parasites of Plasmodium fieldi and Plasmodium simiovale, 2 simian malaria parasites related to the human malaria parasite Plasmodium ovale, were cultured in vitro by inoculating primary cultures of hepatocytes from rhesus monkeys (Macaca mulatta) with sporozoites. Less than 1% of sporozoites developed into schizonts for either species. Structure and size of the liver stages in both species were similar to previous in vivo descriptions, and the time required for in vitro maturation correlated well with the prepatent periods described for each species. Such monkey models could be very useful in conducting scientific investigations on the pre-erythrocytic stages of P. ovale-like malaria parasites. PMID- 8195941 TI - Extraembryonic membranes of the endoparasitic wasp Cotesia congregata: presence of a separate amnion and serosa. AB - Little information is available describing the development of endoparasitic Hymenoptera prior to hatching of the first instar larva. The present study reveals that in Cotesia congregata, and likely other braconid wasp parasites, the serosa and amnion comprise separate layers encasing the developing first instar larva. Examination of newly hatched first instar parasites in the hemocoel of Manduca sexta confirmed that the larvae were ensheathed in the remnants of an "amnion" at hatching, with patches of nucleated cells seen adhering in thin sheets to the larva. The amnion is delaminated from a cellular serosal membrane that lies directly beneath the chorion, which subsequently gives rise to teratocytes. Scanning electron micrographs indicate that remnants of the amnion remained associated with the larvae for a longer period posthatch than did the teratocytes, which rapidly dispersed into the host hemolymph. The presence of an amnion-like layer in braconid endoparasitic wasps may prove to be significant with respect to our understanding of host-parasite immunological interactions occurring during the initiation of the relationship of the parasites with their host. PMID- 8195942 TI - Excess positive associations in communities of intestinal helminths of bats: a refined null hypothesis and a test of the facilitation hypothesis. AB - The null hypothesis that the number of positive pairwise covariances should equal the number of negative pairwise covariances in samples from communities of randomly associated helminth species was reevaluated. The proportion of positive covariances in a sample from a community of independent species depends upon the proportion of rare species (prevalence less than 10%), the proportion of common species (prevalence greater than 90%), and the size of the sample of hosts. If rare species dominate, then there will be an excess of negative associations; if common species dominate there will be an excess of positive associations. Many helminth communities have more rare than common species, therefore samples from communities that show an equal number of positive and negative covariances have a greater number of positive associations than is expected for randomly associated species. Increased sample size will reduce the sampling bias, but at least 100 hosts are necessary and often 500-7,500 hosts are required. The excess of positive covariances between helminth species in 10 populations of bats disappeared after restricting the analyses to hosts in which both members of a species pair were present. This result suggests that excess positive associations between helminth species in bats are due to joint presences and absences in hosts rather than to interspecific facilitation. Interspecific facilitation would be supported by observed positive correlations between the intensities of individuals of the species pairs. PMID- 8195943 TI - Effects of hormones and cysteine protease modulators on infection of HepG2 cells by Plasmodium berghei sporozoites in vitro determined by ELISA immunoassay. AB - An enzyme-linked immunosorbent assay (ELISA) detecting a Plasmodium berghei liver stage-specific protein Pbl-1 is described. The quantitative detection limits ranged from 0.01 to 0.05 microgram of parasite protein. Qualitatively the assay detected as little as 0.001 microgram Pbl-1 per well. Using the ELISA dexamethasone and insulin together was shown to promote higher parasite infections in HepG2 cells compared to unsupplemented medium. Anti-cowpea-protease cysteine inhibitor significantly increased hepatocyte invasion as compared to controls, whereas a significant decrease was recorded in the presence of the protease inhibitor E64. Partial involvement of cysteine proteases in HepG2 invasion by P. berghei sporozoites is therefore suggested. PMID- 8195944 TI - Identification of Schistosoma mansoni antigens recognized by T cells of C57BL/6 mice immunized with gamma-irradiated cercariae. AB - Immunization of C57Bl/6 mice with gamma-irradiated Schistosoma mansoni cercariae induces highly significant protection against subsequent challenge with unattenuated living cercariae. The antigens that evoke T cell-mediated immunity in this model are vaccine antigen candidates since T lymphocytes mediate antibody independent immune responses and control the production of most antibodies. To identify these antigens, spleen cells of mice immunized twice with gamma irradiated cercariae were tested for proliferative responsiveness and production of interleukins (Il) and interferon-gamma (IFN-gamma) following incubation with separated soluble schistosomular (SSA) and adult worm (SAWA) antigens in T cell western assays. Data obtained at 3, 4, 5, and 6 wk post-secondary immunization in 2 experiments indicated that SSA and SAWA bands of 62-60, 50, and 45 kDa reproducibly elicited T cell proliferation and production of Il-2, Il-4, and IFN gamma by spleen cells from immunized, but not unimmunized, mice. Bands of 72-68, 29.5, and 28 kDa elicited proliferation and production of Il-2 and Il-4, but not IFN-gamma. Bands of 35-33 and 24 kDa induced either proliferation or Il production at some intervals. PMID- 8195945 TI - Trypanosoma cruzi affects nitric oxide production by murine peritoneal macrophages. AB - Macrophages from mice that are infected with various intracellular pathogens including Leishmania major, Trypanosoma cruzi, and Salmonella typhimurium are stimulated to produce large quantities of nitric oxide (NO). Both viable and heat treated L. major amastigotes have been shown to be effective co-signals for NO production in vitro. NO produced by macrophages has anti-microbial and immunosuppressive functions in an immune response. We have shown previously that NO plays a complicated role in T. cruzi infections since macrophages are important both in mediating an immune response against the parasite as well as in mediating immunosuppression. In this study we examined how T. cruzi affects NO production by macrophages from C3HeB/FeJ and C57BL/6 mice in vitro. We found that live trypomastigotes neither stimulate nor decrease NO production by interferon (IFN)-gamma-activated macrophages. However, heat-treated or glutaraldehyde-fixed trypomastigotes of T. cruzi significantly decrease NO production by IFN-gamma activated macrophages and as a result decrease macrophage-mediated trypanocidal and immunosuppressive activity. We have determined that this decrease in NO production by T. cruzi is not due to stimulation of transforming growth factor beta production and involves tumor necrosis factor-alpha only in C3HeB/FeJ macrophages. This study demonstrates the complexity of the T. cruzi-macrophage interaction as well as confirms previously demonstrated differences between macrophages from 2 strains of mice. PMID- 8195946 TI - Evaluation of the safety and efficacy of vaccination of nursing pigs with living tachyzoites of two strains of Toxoplasma gondii. AB - The safety of vaccination and persistence and distribution of Toxoplasma gondii stages within tissues following vaccination were examined in 3-day-old nursing pigs vaccinated with living tachyzoites by intravenous and subcutaneous routes of either the TS-4 mutant strain or its parent RH strain of T. gondii. The efficacy of vaccination of nursing pigs with the TS-4 mutant was also examined in pigs challenged orally with oocysts following vaccination. Pigs were vaccinated with 3 x 10(5) living tachyzoites when 3 days old and boosted with 3 x 10(5) living tachyzoites when 17 days old. Group 1 had 2 pigs vaccinated intravenously (i.v.) with Hanks' balanced salt solution (HBSS) and served as a vaccination control. Group 2 and 5 pigs vaccinated i.v. with tachyzoites of the TS-4 mutant; 3 pigs were used to examine the safety, persistence, and distribution of the TS-4 mutant and 2 were used for oocyst challenge. Group 3 had 5 pigs vaccinated i.v. with tachyzoites of the RH strain and all were used to examine the safety, persistence, and distribution of the RH strain within their tissues. Group 4 had 3 pigs vaccinated subcutaneously (s.c.) with tachyzoites of the TS-4 mutant; 1 was used to determine the persistence and distribution of the TS-4 mutant within its tissues and the other 2 pigs were used for GT-1 oocyst challenge studies. Group 5 had 3 pigs vaccinated s.c. with tachyzoites of the RH strain and all were used to examine the safety, persistence, and distribution of the RH strain within their tissues. None of the control pigs or pigs vaccinated with the TS-4 mutant developed clinical signs of disease or died prior to oocyst challenge. The TS-4 mutant was not reisolated from the tissues of vaccinated pigs nor were microscopic lesions present in the tissues of pigs that had been killed and examined at necropsy. Severe disease with clinical signs consisting of dyspnea, inactivity, diarrhea, and ocular lesions was observed in the group 3 pigs vaccinated i.v. with the RH strain. One pig died 7 days after initial vaccination. Microscopic lesions were observed in numerous tissues of all group 3 pigs. Swelling, erythema, and ulcers were observed at the site of inoculation in the group 5 pigs that were vaccinated s.c. with the RH strain. Minimal to no microscopic lesions were observed in these group 5 pigs. The RH strain was reisolated from pigs in both groups vaccinated with this strain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8195947 TI - Transfer of resistance to Schistosoma mansoni in Biomphalaria glabrata by allografts of amoebocyte-producing organ. AB - Allografts of amoebocyte-producing organ (APO) were implanted heterotopically into the schistosome-susceptible NIH albino stock of Biomphalaria glabrata from either 13-16-R1 (a schistosome-resistant stock) or NIH albino donors. At 3, 7-8, 14-15, 21, 28-33, or 47-71 days postimplantation (PI), allograft recipients were exposed to 50 miracidia each of Schistosoma mansoni and subsequently monitored for development of sporocysts and cercariae. Relative to untampered snails and recipients of NIH albino APOs, recipients of 13-16-R1 APOs showed significantly lower infection rates from 7 days PI until the end of the experiment. The mechanism for this apparent transfer of resistance is unknown, but hypothetically it may involve chimerism, i.e., production of hemocytes with the resistant phenotype by implanted 13-16-R1 APOs, or synthesis by the implant of soluble "resistance factors" that induce cytotoxicity in recipient hemocytes, or both. PMID- 8195948 TI - Influence of storage and examination methods on the recovery and size of metacercariae of Cyathocotyle bushiensis and Sphaeridiotrema pseudoglobulus (Digenea). AB - The recovery of metacercariae of Cyathocotyle bushiensis (Digenea: Cyathocotylidae) and Sphaeridiotrema pseudoglobulus (Digenea: Psilostomidae) from Bithynia tentaculata (Gastropoda: Prosobranchia) subjected to 3 methods of storage (70% alcohol, freezing, and fresh) and 2 methods of examination (crushing or artificial digestion) was evaluated. Prevalence and abundance of fully developed metacercariae of C. bushiensis and metacercariae of S. pseudoglobulus did not significantly vary as a result of storage or examination methods; however, digestion of frozen and fresh snails resulted in a significantly lower prevalence and abundance of not fully developed metacercariae of C. bushiensis. Furthermore, freezing or storing snails in alcohol may result in misclassification of the metacercariae of C. bushiensis. Both methods of storage and examination also affected the size of the metacercariae of both digeneans. Although digested snails were easier to examine, there appeared to be no overall gain in time by using digestion instead of crushing. PMID- 8195949 TI - Developmental and morphological characteristics of Taenia taeniaeformis (Batsch, 1786) in Clethrionomys rufocanus bedfordiae and Rattus norvegicus from different geographical locations. AB - Developmental and morphological characteristics of 3 isolates of Taenia taeniaeformis isolated from Clethrionomys rufocanus bedfordiae in Abuta (70 km southwest of Sapporo), Japan (isolate ACR), and from Rattus norvegicus in Sapporo, Japan (isolate SRN) and Kuala Lumpur, Malaysia (isolate KRN) were compared. Eggs of 3 isolates were administered to several species of rodents. Isolate ACR infected C. rufocanus bedfordiae, Apodemus speciosus, and Apodemus argenteus, but not rats or mice, whereas isolate SRN and isolate KRN were infective to rats, mice, A. speciosus, and A. argenteus, but not to C. rufocanus bedfordiae. The increase in cyst size of isolate ACR continued during the experimental period, whereas that of the other 2 isolates had ceased growing after 30 days postinfection. However, significant differences were observed in the length of the small rostellar hooks, number and distribution of testes, and the length of the cirrus sac between isolate ACR and the other 2 isolates. Thus it is suggested that isolate ACR is a distinct strain or even a new species. PMID- 8195950 TI - Presence and localization of vinculin in Giardia. AB - A requisite element of pathogenicity in Giardia infections is the parasites' ability to adhere to the intestinal epithelial brush border. The presence of vinculin in Giardia was studied because this protein is known to link the cytoskeleton to the plasma membrane and is localized at adhesion foci in many cell-cell and cell-substrate contact sites. Actin, alpha-actinin, and vinculin were identified in Giardia by western blot analysis. Giardia trophozoites attached to glass substrates were examined by interference reflection microscopy (IRM) and immunofluorescence. The IRM defined the lateral crest, bare area, and overlap region of the ventral disk, as well as the ventrolateral flange and lateral shields as close contact areas between parasite and substrate. These close contact regions were then correlated with immunofluorescence localization of actin, alpha-actinin, and vinculin. Actin was seen in the lateral crest, while alpha-actinin was observed in the ventral disc periphery and lateral shields. Vinculin was viewed at the bare and overlap areas of the ventral disc and portions of the lateral crest, as well as the ventrolateral flange and lateral shields. The correspondence of close contact sites with vinculin localization suggests a role for vinculin in Giardia attachment and adherence. PMID- 8195951 TI - Improvement of the merthiolate-iodine-formalin (MIF) fecal technique for hookworm, Trichuris trichiura, and Ascaris lumbricoides eggs. AB - The merthiolate-iodine-formalin (MIF) technique to detect human intestinal parasites in feces was inefficient for the detection of hookworm and Trichuris trichiura eggs. Addition of a saturated-brine flotation step increased recovery of hookworm eggs by 77% and Trichuris trichiura eggs by 87%. Recovery of Ascaris lumbricoides also was increased by 71%. This was a significant improvement in the sensitivity of the MIF technique for these 3 kinds of human parasite. PMID- 8195952 TI - A report of Dactylogyrus amphibothrium (Monogenea) on the gills of European ruffe in western Lake Superior. AB - The Eurasian monogenean Dactylogyrus amphibothrium Wagener, 1857 is reported from the gills of ruffe (Gymnocephalus cernuus) in western Lake Superior. The parasite must have arrived with fish discharged with ship ballast in the mid 1980s. It is the 12th species of monogenean known to have been introduced and established with its host in North America. PMID- 8195953 TI - Helminths of the black bear, Ursus americanus, in New Brunswick. AB - Between May 1989 and October 1991, 544 black bears Ursus americanus were collected in New Brunswick and examined for Trichinella spiralis larvae. In addition, 110 of these bears were examined for filarial nematodes, and the entire intestinal tracts of 12 bears were examined for intestinal helminths. Four species of helminths were identified from these bears, including Trichinella spiralis, Dirofilaria ursi, Baylisascaris transfuga, and Taenia krabbei. This represents the first documentation of T. spiralis in Maritime Canada and extends eastward the range of T. krabbei. PMID- 8195954 TI - Synonymy of Longibucca eptesica with Longibucca lasiura (Nematoda: Rhabditoidea) and new host and geographic records. AB - The genus Longibucca Chitwood, 1933 (Nematoda: Rhabditoidea) is reviewed based on examination of museum and adult specimens collected from 4 species of bats (Myotis lucifugus, Myotis ciliolabrum, Eptesicus fuscus, and Lasionycteris noctivagans) in Alberta, Canada. Two species are considered valid, namely Longibucca vivipara Chitwood, 1933, and Longibucca lasiura McIntosh and Chitwood, 1934. Longibucca eptesica Elsea, 1953 is considered a synonym of L. lasiura. New hosts of Longibucca lasiura include Pipistrellus subflavus, Lasionycteris noctivagans, and Myotis ciliolabrum. New geographic ranges of Longibucca lasiura are Virginia, U.S.A., Canada, and western North America. PMID- 8195955 TI - Plasmodium vivax sporozoite rates from Anopheles albimanus in southern Chiapas, Mexico. AB - Anopheles albimanus mosquitoes were collected from August 1984 to November 1987 on intra- and peridomicile human bait in Rancheria El Gancho, Chiapas, Mexico. The mosquitoes were desiccated and stored in silicon chambers from 3 mo to 3 yr post-collection prior to being assayed using a direct enzyme-linked immunosorbent assay to detect Plasmodium vivax predominant-type sporozoite protein. Peridomicile-collected mosquitoes had a 10-fold higher sporozoite rate than those collected indoors, but only the latter correlate significantly with the seasonal human parasite index. Mosquito sporozoite burden was also significantly higher in the peridomicile-collected population. PMID- 8195956 TI - Ivermectin binding sites in sensitive and resistant Haemonchus contortus. AB - Membranes from both ivermectin-sensitive and -resistant Haemonchus contortus L3 larvae were examined for the presence of high affinity [3H]ivermectin binding sites. Both tissue preparations displayed high affinity drug binding sites (Kd = 0.13 nM). Receptor density (Bmax = 0.4 pmol/mg) was the same in both the sensitive and resistant nematodes suggesting that target site modification was not involved in the development of drug resistance in this particular strain of H. contortus. The H. contortus ivermectin binding site appeared to be similar to the well characterized Caenorhabditis elegans ivermectin binding site with respect to affinity for ivermectin and receptor density. PMID- 8195957 TI - A species of Plasmodium from sandhill cranes in Florida. AB - Infections of a species of Plasmodium (subgenus Giovannolaia) were diagnosed in 3 sandhill cranes (Grus canadensis) from north-central Florida. This parasite is close morphometrically to Plasmodium polare; this finding constitutes the first report of a species of Plasmodium from sandhill cranes in North America. PMID- 8195958 TI - The value of flash visual evoked potentials in albinism. AB - In albinism, the majority of temporal retinal fibers serving the nasal visual field cross at the chiasm and project to the contralateral hemisphere. This misrouting is seen in hemispheric asymmetries present in the visual evoked potential (VEP). Misrouting of retinal fibers was also thought to occur in dissociated vertical deviation, Prader-Willi syndrome, and perhaps carrier states of albinism. However, recent literature is reaching the conclusion we have drawn in our laboratory: only albinism shows VEP hemispheric asymmetries that reverse when the other eye is stimulated. Use of different stimuli, recording conditions, and response criteria among investigators has created some confusion in differentiating what constitutes asymmetry. We conclude that use of a diffuse flash stimulus and a bipolar electrode derivation that compares differences between the left and right occipital hemispheres will clearly differentiate albinism from all other conditions, making it especially useful in a pediatric population. PMID- 8195959 TI - Clinical variations of trilateral retinoblastoma: a report of 13 cases. AB - Of 440 consecutive children with retinoblastoma whom we treated between April 1972 and April 1992, 13 (3%) developed a midline intracranial neoplasm. Four of these 13 patients had bilateral familial retinoblastoma, 7 had bilateral sporadic retinoblastoma, and 1 patient had unilateral familial retinoblastoma. The twin brother of the latter patient developed pinealoblastoma without retinoblastoma. In this series, the incidence of trilateral retinoblastoma was 8% of all bilateral familial retinoblastoma and 5% of all bilateral sporadic retinoblastoma. The retinoblastoma was diagnosed at a mean age of 4.5 months and the midline intracranial tumor was diagnosed at a mean age of 23 months. The mean time interval between the diagnosis of retinoblastoma and the intracranial tumor was 22 months (range, 0 to 48 months). Seven patients (55%) were asymptomatic and their intracranial neoplasm was found on routine brain-imaging studies. The primary intracranial neoplasm had a pineal location in 10 cases and parasellar location in three cases. Despite aggressive combined treatment, 12 patients (92%) have died at a mean interval of 11 months after the diagnosis of intracranial malignancy. The mean survival of patients with midline intracranial neoplasm who were asymptomatic was significantly longer than that of symptomatic patients (P = .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195960 TI - Changing trends in the management of retinoblastoma: 1951-1965 vs 1966-1980. AB - A retrospective analysis of the records of 1253 retinoblastoma patients (567 females, 665 males, and sex of one unknown) seen in the years 1951-1965 (575 patients, Interval I) and 1966-1980 (678 patients, Interval II) was conducted to determine changes in the manner of presentation of the disease, the treatment modalities employed, and their subsequent outcomes following treatment. There was no significant difference between the two 15-year time intervals in the age at presentation (mean, range), laterality, gender, family history, laterality vs gender distribution, family history vs laterality, employment of chemotherapy in unilateral cases or the use of external beam radiation (EBR) in bilateral cases. Changing trends in the management of retinoblastoma were observed as a result of the introduction of new treatment modalities, such as cryotherapy, light coagulation, and radioactive plaque therapy. Bilateral patients have received chemotherapy less frequently in interval II. The use of photocoagulation, cryotherapy, and brachytherapy for bilaterals, and cryotherapy for unilaterals increased significantly during Interval II. During both time intervals, a significantly higher percentage of unilaterally affected eyes were enucleated compared with bilaterally affected eyes; in addition, there was a decrease in the percentage of enucleations performed on both unilaterally and bilaterally affected eyes. In Interval II, 87% of unilateral patients and 91% of the bilateral patients had an enucleation performed. PMID- 8195961 TI - Leber congenital amaurosis and its association with keratoconus and keratoglobus. AB - Leber congenital amaurosis has been associated with keratoconus and it has been postulated that this is due to eye rubbing, the oculo-digital sign, because of poor vision. Six schools for the blind were visited, and 174 children with a visual acuity of less than 3/60 examined. Thirty-five children had Leber amaurosis, and 10 of these had keratoconus (29%) and one had keratoglobus (3%). The six pedigrees of the cases with Leber amaurosis and keratoconus are presented in detail. Only 3 of the 139 other blind children had keratoconus (P < .05) and 1 had keratoglobus. Keratoconus seems specifically associated with Leber amaurosis, probably due to genetic factors, rather than poor visual acuity per se. PMID- 8195962 TI - Congenital ocular defects associated with an abnormality of the human chromosome 1: trisomy 1q32-qter. AB - This article describes the detailed ocular pathology found in a premature neonate, born at 34 weeks, with multiple congenital anomalies resulting from de novo trisomy 1q32-qter. The ocular defects include goniodysgenesis, persistent tunica vasculosa lentis and hyaloid vessels, hypopigmentation of the posterior iris epithelium, ectopia of the ciliary processes, and abnormal insertion of the ciliary muscle and cataract. This is the first report of the detailed ocular pathology in a case of trisomy 1q and is also unusual in that the chromosomal defect has apparently arisen de novo in the proband. PMID- 8195963 TI - Vascular patterns in orbital rhabdomyosarcoma. PMID- 8195964 TI - Recurrent giant orbital dermoid of infancy. PMID- 8195965 TI - Varicella dendritic keratitis. PMID- 8195966 TI - Different manifestation of Rieger syndrome in monozygotic twins. PMID- 8195967 TI - Congenital undifferentiated sarcoma of the orbit. PMID- 8195968 TI - Preoperative alternate occlusion decreases motion processing abnormalities in infantile esotropia. AB - We have examined the effects of preoperative, full-time alternate occlusion on the development of visual motion processing mechanisms. Motion visual evoked potentials (MVEPs) were recorded longitudinally in 14 infantile esotropia patients during the course of standard preoperative occlusion therapy. The MVEP in these patients was initially asymmetric in a fashion consistent with a nasalward/temporalward response bias, with a motion asymmetry significantly higher than that of age-matched normals. The magnitude of the developmental motion asymmetry declined significantly after an average of 24 weeks of alternate occlusion. This result implies that the binocular motion-sensitive cells underlying the MVEP retain some degree of plasticity up to at least 1 year of age. Our data suggest further that the persistence of motion asymmetries in untreated infantile esotropia patients is maintained by an active process that can be disrupted by alternate occlusion. Alternate occlusion apparently eliminates a form of abnormal binocular interaction that supports the persistence of the motion asymmetry. We propose that one of the necessary pre-conditions for symmetricization of motion processing in infantile esotropia is the absence of abnormal competitive binocular interactions. PMID- 8195969 TI - Lacrimal gland choristoma of the conjunctiva simulating a squamous cell carcinoma. PMID- 8195970 TI - Strabismus repair is not "cosmetic". PMID- 8195971 TI - Dentin hypersensitivity. Occlusion of dentinal tubules by brushing with and without an abrasive dentifrice. AB - Daily toothbrushing with and without an abrasive dentifrice was performed on the ground surfaces of human cervical dentin attached to resin plates, which had been exposed to the oral cavities of 4 subjects for 8 weeks. Brushing with a dentifrice containing calcium hydrogen phosphate as an abrasive caused most of the dentinal tubules to open. The patency of dentinal tubules is thought to induce dentin hypersensitivity. Brushing without a dentifrice, on the other hand, resulted in occlusion of the dentinal tubules with organic pellicle-containing minerals. Furthermore, abrasion did not occur; however, no bacterial plaque or dental calculus were retained. The occluded tubules which were distributed over the entire dentin surfaces will likely prevent hypersensitivity. Such organic mineral materials occluding the tubules can be derived from saliva and embedded by the brushing. We suggest that use of a non-abrasive dentifrice will prevent or reduce dentin hypersensitivity in the cervical regions. PMID- 8195972 TI - Structural and functional changes of cementum surface following exposure to a modified Nd:YAG laser. AB - A modified Nd:YAG laser was evaluated for its effect on root cementum topography and fibroblastic attachment. Fifteen extracted human teeth were curetted, sectioned, and divided into 60 areas representing 4 groups. Group I were non lased controls, while groups II, III, and IV were lased with the same power (4 watts, 1 second), but at 3 different laser-target distances (1, 3, and 5 mm), thus delivering 3 different energy levels. Following lasing, 20 areas (5 per group) were examined under SEM for detection of any structural changes. Human gingival fibroblasts were cultured on both experimental and control samples of the remaining 40 areas. Photomicrographs at x 500 were obtained and the number of attached fibroblasts were counted. Results showed that lased cemental surfaces exhibited changes in surface topography which ranged from what appeared to be an apparent fusion of the surface of the covering smear layer (lowest energy level), to cracking and fissuring of the lased surface (highest energy level). When fibroblasts were cultured on the specimens, the results demonstrated the presence of a monolayer of cells on the control surfaces and on the surfaces lased with the lowest energy level (5 mm distance). Specimens lased at the mid-energy level (3 mm) showed decreased numbers of attached cells, but not significantly different from the controls. On the other hand lasing the cementum surface at the highest energy level (1 mm distance) caused a significant decrease in the number of the attached cells as compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195973 TI - Influence of tooth instrumentation roughness on subgingival microbial colonization. AB - This study evaluated microbial colonization of periodontal pockets subjected to root instrumentation with a curet or a rotating diamond. Ten maxillary and 10 mandibular subgingival pockets were established in the canines of 5 beagle dogs. The subgingival root surface areas were debrided by a sharp curet or a flame shaped, fine-grained, rotating diamond point. The dogs were fed a plaque-inducing diet for 70 days. Specimens from both instrumentation groups were then harvested and prepared for stereomicroscopic and scanning electron microscopic evaluation. Grading of the extent of subgingival colonization was performed in coded specimens directly on the fluorescent screen of the scanning electron microscope in a grid-counting system. Error of the method was assessed by duplicate counts. The subgingival root surface areas were divided into 3 zones: cervical, middle, and apical, and statistical differences between these zones as well as between the 2 instrumentation groups were calculated. The results revealed that curet treated surfaces were smoother and promoted less subgingival colonization than diamond-treated surfaces. The difference in amount of bacterial colonization between the 2 groups was statistically significant (P < 0.05) in all zones. Bacterial colonization decreased in apical direction in both instrumentation groups. For the diamond-treated specimens, this decrease was significant (P < 0.05) between each of the 3 zones. In the curet-treated specimens, the decrease was significant only between the cervical and the apical zone (P < 0.05). The present study has demonstrated that subgingival instrumentation roughness significantly influences the subgingival microbial colonization. PMID- 8195974 TI - Flow-cytometric identification and detection of Porphyromonas gingivalis by a LPS specific monoclonal antibody. AB - The purpose of this study was to identify Porphyromonas gingivalis (P. gingivalis) by flow cytometry (FCM) using a monoclonal antibody (MAb) OMR-Bg1E directed to P. gingivalis-specific lipopolysaccharide (LPS). The P. gingivalis strains ATCC 33277, 381, ESO75, W50, and A7A1 were selected for the study. Fusobacterium nucleatum (F. nucleatum), Prevotella intermedia (P. intermedia), Campylobacter rectus (C. rectus), Streptococcus sanguis (S. sanguis) and Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) served as controls. A suspension of 10(7) bacteria/ml of each bacteria was prepared and then reacted with a P. gingivalis specific MAb OMR-Bg1E and fluorescein isothiocyanate (FITC) labeled second antibody. These samples were analyzed by FCM. Bacterial specific binding aggregate on data was separated out by the forward- and side-angle-scatter characteristics, while non-specific binding (NSB) was eliminated by excluding the region with mouse IgG-positive and second antibody-positive area. FCM detected a mean range of 56.2% to 97.2% P. gingivalis strains. There was a 5.1% non-specific binding using FCM to non-P. gingivalis strains. When the P. gingivalis concentration was adjusted to 10(2), 10(4), and 10(6) bacteria/ml, a detection rate of 35.7%, 48.1%, and 91.4%, was respectively observed. The lower sensitivity of the flow cytometric assay was 10(2) bacteria/ml. When P. gingivalis was added to P. intermedia suspension at 1, 20, 40, 60, and 80%, the MAb-positive fraction yielded by FCM displayed a coefficient of determination of 0.967 with the actual percentage of P. gingivalis and could be regressed to a linear function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195975 TI - Incidence of attachment loss in community-dwelling older adults. AB - Since 1985, only four studies have been published that present data on attachment loss in populations. The purpose of this study was to present the incidence of attachment loss over an 18-month period in a representative sample of community dwelling older adults. In addition, the utility of multivariate prediction models to distinguish between people who will and will not experience disease progression was explored. The Piedmont 65+ Dental Study of the Elderly is a longitudinal investigation of a random sub-sample of over 1,000 community dwelling people over the age of 65 in five contiguous North Carolina counties. The five dentists who conducted the in-home examinations and interviews at baseline also participated at 18 months and examined the same subjects. The overall attrition rate for blacks was 27% and the rate for whites was 23%. At 18 months, the baseline attachment level scores for those subjects who were lost from the study were not significantly different from the scores of those who remained in the study. A change in attachment loss of 3 mm or more over the 18 months was set as a conservative estimate of actual change taking place. Blacks were significantly more likely to experience attachment loss irrespective of the number of sites involved (P < .05). Approximately half the people had at least one losing site and about one-third of the blacks and one-fourth of the whites had at least two losing sites. A total of 24% of blacks and 16% of whites had 3 or more losing sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195976 TI - The effect of a light-cured periodontal dressing material on HeLa cells and fibroblasts in vitro. AB - The effect which a visible light-curing periodontal dressing material based upon a urethane dimethacrylate resin has upon HeLa cells and fibroblasts in its uncured and fully cured states has been studied in vitro. Fully-cured material has no effect on either cell type. Uncured material produces a surrounding zone of growth inhibition and cell death on direct contact. Inhibition is caused by the release into the medium of substances toxic to cells. However, this growth inhibition is overcome in time (5 days). It is suggested that partly-cured material containing residual free monomer in contact with a healing gingival site could impede rapid repair. Nuclear magnetic resonance microimaging has shown that in places where there is a greater depth of material (e.g., interproximal regions) this underlying material may be partly cured. Increasing the exposure to the curing light will prevent (or minimize) the presence of partly-cured material; the fully-cured material being compatible with the cells. PMID- 8195977 TI - Technetium 99m-MDP scintigraphy of patients undergoing implant prosthetic procedures: a follow-up study. AB - The clinical evaluation of peri-implant tissue is mainly based on x-rays. In recent years, radioisotope scintigraphy using Tc-99m-MDP (technetium-99m methylene diphosphonate) proved to be a useful and reliable clinical method for measuring increased metabolic activity at specific sites of the skeletal tissue. Twenty-six (26) patients (26 to 75 years) who were diagnosed for implant prosthetic treatment modality were randomly chosen to participate in this study. Each patient was injected with 20 mCi of Tc-99m-MDP was scanned 2 hours later by gamma-camera for isotope uptake levels in the jaws. Each patient was scanned 1 to 4 times, starting 2 weeks after implant surgery and up to the 40th week postsurgery. Blade and screw type implants using the non-submerged, one-stage technique were placed. Therefore, the prosthetic reconstruction was initiated 2 weeks after implant surgery. In order to compare the different scans we formulated a relative "bone scan index" (BSI). The results of 62 scans were plotted as BSI against time after implant surgery. A mathematical regression analysis of the BSI was also performed. At the initial stage of 2 to 3 weeks after surgery the BSI is high and then gradually declines. While BSI of the implants in the mandible reaches baseline levels after 12 weeks, the BSI in the maxilla reaches baseline only after 20 weeks. On the other hand, there was no difference in BSI with regard to blade or screw type implant. Here we were able to demonstrate that the process is independent of implant modality and depends on the specific metabolic properties of the jaw.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195978 TI - The inhibition of interferon-gamma-induced upregulation of HLA-DR expression on cultured human gingival fibroblasts by interleukin-1 beta or tumor necrosis factor-alpha. AB - The purpose of this study was to examine the effect of inflammatory cytokines on IFN-gamma-induced HLA-DR expression on cultured human gingival fibroblasts by flow cytometry. Natural human IFN-gamma, recombinant human interleukin-1 beta (rhIL-1 beta), and rh tumor necrosis factor-alpha (rhTNF-alpha) were used. IFN gamma-induced upregulation of HLA-DR expression was inhibited by simultaneously adding rhIL-1 beta or rhTNF-alpha (65.9% and 31.4% inhibition, respectively). Both rhIL-1 beta and rhTNF-alpha induced endogenous prostaglandin E2 (PGE2) from gingival fibroblasts, while IFN-gamma did not. The inhibitory effect of rhIL-1 beta or rhTNF-alpha on IFN-gamma-induced upregulation of HLA-DR expression was partially abated in the presence of indomethacin (reductions of 65.9% and 41.7%, respectively). Both rhIL-1 beta- and rhTNF-alpha-induced endogenous PGE2 synthesis were completely inhibited by adding indomethacin (P < 0.001). The addition of exogenous PGE2 inhibited the IFN-gamma-induced HLA-DR expression (P < 0.001). These observations suggest that the MCH class II expression on human gingival fibroblasts are influenced by the cytokine network and indirectly by the cytokine-mediated fibroblast PGE2. PMID- 8195979 TI - Clinical evaluation of HTR polymer bone replacement grafts in human mandibular Class II molar furcations. AB - A biocompatible microporous composite of PMMA (poly-methyl-methacrylate), PHEMA (poly-hydroxyl-ethyl-methacrylate), and calcium hydroxide (HTR) or autogenous osseous coagulum (AOC) bone replacement grafts were evaluated in 15 pairs of mandibular molar Class II furcations in 9 patients. Following initial preparation, full thickness flaps were raised to gain access to the furcations; mechanical hand and ultrasonic root and defect debridement and chemical (tetracycline) root preparation were performed; paired furcations in each patient were randomly grafted with either HTR or AOC; and the host flaps replaced or slightly coronally positioned. Weekly, then monthly, deplaquing was performed until surgical re-entry at 6 to 12 months. Both treatments improved the clinical status of the treated furcations. Direct clinical measurements demonstrated essentially equivalent clinical results with both bone replacement graft materials related to most hard and soft tissue changes in the furcations. Differences in favor of HTR were found for horizontal residual furcation depth (2.4 mm vs. 3.9 mm), horizontal furcation fill (1.9 mm vs. 0.8 mm), and percent horizontal furcation fill (44.4% vs. 17.1%) (all P < or = 0.05 paired t test). These favorable results with HTR polymer are similar to several reports with other graft materials and with GTR barriers, and suggest that HTR polymer may be a useful therapeutic adjunct in the clinical management of grade II mandibular molar furcations. PMID- 8195980 TI - Periodontal repair in dogs: space provision by reinforced ePTFE membranes enhances bone and cementum regeneration in large supraalveolar defects. AB - Regeneration of alveolar bone and cementum following reconstructive therapy with reinforced space providing expanded polytetrafluorethylene (ePTFE) membranes was evaluated in supraalveolar mandibular premolar periodontal defects in five beagle dogs. The surgically-created defects in contralateral jaw quadrants were randomly assigned to receive the dome-shaped membrane or serve as surgical control. Flaps were positioned to completely submerge the teeth and sutured. The dogs were sacrificed 8 weeks after surgery and tissue blocks including teeth and surrounding structures processed for histology. Membrane treated defects in two animals became exposed and infected leaving intact quadrants in three dogs for histometric analysis. Parameters evaluated included defect height, height and area of regenerated alveolar bone, height of regenerated cementum, root resorption, and ankylosis. Mean defect height approximated 4.1 mm. Mean height (+/- s.d.) of regenerated alveolar bone amounted to 2.9 +/- 0.6 and 0.6 +/- 0.2 mm for membrane and control defects, respectively (P = 0.006). Corresponding values for bone area were 1.4 +/- 0.7 and 0.4 +/- 0.4 mm2 (P = 0.02). Cementum regeneration was observed in all teeth averaging (+/- s.d.) 1.6 +/- 0.3 mm for membrane treated and 0.1 +/- 0.1 mm for control defects (P = 0.01). Small amounts of root resorption were seen in all teeth with no significant difference between treatments. Ankylosis was noticed in three membrane treated and two control teeth. The present study provides a biologic rationale for space provision for enhanced bone and cementum regeneration in periodontal defects subject to reconstructive therapy. PMID- 8195981 TI - Impaired bactericidal activity of PMN from two brothers with necrotizing ulcerative gingivo-periodontitis. AB - The purpose of this study was to investigate the pathogenesis of necrotizing ulcerative gingivo-periodontitis (ANUP) diagnosed in two brothers, age 9 (ANUP1) and 14 (ANUP2) from rural Egypt. Complete blood count, differential and blood chemistry were within normal limits for both brothers and they were not malnourished. The phagocytosis and killing function of their polymorphonuclear leukocytes (PMN) towards four bacterial species were assessed using a fluorochrome microassay. The selection of bacterial species was based on preliminary microbiological results in early onset periodontitis in Egypt. Fluorochrome-labeled Prevotella intermedia, Peptostreptococcus micros, Campylobacter rectus, and Porphyromonas gingivalis were pre-opsonized with ANUP serum and added to PMN from both ANUP patients, as well as PMN from three sex matched and two sex- and age-matched healthy Egyptian control (CTL) subjects. We found significant depressions (P < 0.05) in PMN phagocytosis and killing of C. rectus and P. intermedia by ANUP1 and ANUP2, when compared to all CTL PMN. An assessment of the Gram-negative subgingival microflora present in both ANUP patients (in colony forming unit percent of total CFU recovered) (CFU %) revealed the presence of P. intermedia (ANUP1, 41.7 CFU %; ANUP2, 14.8 CFU %), Fusobacterium nucleatum (ANUP1, 3.6 CFU %; ANUP2, 48.1 CFU %), and Veillonella spp. (ANUP1, 18.2 CFU %; ANUP2, 18.5 CFU %). Spirochetes were also observed in cytocentrifuged, Gram-stained plaque from both ANUP patients. The predominant Gram-positive bacterial species recovered from both NUG1 and NUG2 was Streptococcus morbillorum. PMID- 8195982 TI - Clinical, bacteriological, and immunological examinations and the treatment process of two Papillon-Lefevre syndrome patients. AB - Papillon-Lefevre Syndrome (PLS) is a rare disease associated with the early onset of periodontal breakdown in deciduous and permanent dentition. The etiology of the destruction has not been completely clarified. Two female patients (ages 4 and 7 years) with severe destruction of the periodontal structures were examined. Except for palmar and plantar hyperkeratosis, dermatologic examination revealed no other medical disorders. On immunological analysis, measurement of serum antibody titers to 7 periodontopathic bacteria including Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans was performed by enzyme-linked immunosorbent assay (ELISA). Further immunoblot analysis of A. actinomycetemcomitans and microbial culture of samples collected from deep periodontal pockets and mouthrinse solution were performed. The serum of the two patients showed high IgG titer against A. actinomycetemcomitans. Immunoblot results of the two patients against sonicated extract of A. actinomycetemcomitans Y4 strain exhibited a similar pattern. The band pattern differed from that observed in other forms of early onset periodontitis patients or periodontally healthy subjects. Moreover, A. actinomycetemcomitans colonies were cultured in high percentages from the pocket samples. Antibiotic therapy was instituted in addition to conventional periodontal therapy. In the younger patient, all deciduous teeth were extracted as part of the treatment and A. actinomycetemcomitans was no longer detected. All four permanent first molars and 8 permanent incisors subsequently erupted with healthy periodontium. However, the older patient did not improve after periodontal and antibiotic (minocycline and erythromycin) treatments and A. actinomycetemcomitans was consistently detected. Ofloxacin medication finally eliminated A. actinomycetemcomitans from the periodontal pockets. This antibiotic was also associated with reduced gingival inflammation and probing depth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8195983 TI - Reasoning about food and contamination. AB - This article examines strategies that are used to reason about food and contamination. In Experiment 1, Ss refrained from choosing a substance that had been given a "poison" label when the intent of the labeler was ambiguous or malicious but preferred this substance when a rationale was provided that dispelled the implication that there once might have been contaminants present. Experiment 2 was designed to compare the effects of safety on conditional reasoning in food and food-irrelevant contexts. When the safety issue was relevant to food in the form of contamination, subjects were most likely to use formal logic in reasoning. A similar pattern of responses was found in Experiment 3 on tasks for which subjects' ratings of their experience of contexts were matched for plausibility, experience, and danger. The results are discussed in terms of an adaptive constraint that facilitates rationality in reasoning within the food domain. PMID- 8195984 TI - Person memory and judgment: pragmatic influences on impressions formed in a social context. AB - Ss who receive information about a person's traits and behaviors in a social context are likely to focus their attention on the pragmatic implications of this information (i.e., why the information was conveyed). To examine this hypothesis, Ss listened to a taped conversation in which a male target (T) and another speaker (O) exchanged anecdotal accounts of T's behavior. Ss typically used O's trait description of T to form an evaluative concept of O rather than of T, whereas T's trait description of himself had no effect on evaluations of him. Ss had better recall of statements O made when they were unfavorable and, therefore, violated a conversational norm to be polite. However, behaviors that T himself mentioned were often recalled better when they were favorable, and therefore, in violation of a normative expectation to appear modest. The inconsistency of T's behaviors with initial trait descriptions of him had little effect on the recall of these behaviors. PMID- 8195985 TI - Self-evaluation effects of interpersonal versus intergroup social comparison. AB - Two studies tested the prediction that the outcome of social comparison will differ depending on whether interpersonal or intergroup comparison processes have been engaged. Results of an experiment in which college student participants were assigned to membership in a minority or majority social category confirmed the predicted three-way interaction effect of in-group salience, target group membership, and upward-downward comparison on self-assessments of academic ability. Majority group members exhibited contrast effects in their self-ratings following exposure to a videotape of an in-group member displaying either very high or very low academic competence. Self-evaluations of minority group members revealed assimilation effects in response to in-group comparisons and contrast effects in response to out-group comparisons. In a second, follow-up experiment, this in-group assimilation effect was found to be dependent on intergroup contrast. PMID- 8195986 TI - Ideal versus ought predilections for approach and avoidance: distinct self regulatory systems. AB - Two studies using different paradigms activated either ideal self-guides (a person's hopes or wishes) or ought self-guides (a person's sense of duty and responsibility) and measured Ss' concern with different forms of self-regulation: approaching matches to desired end states or mismatches to undesired end states and avoiding mismatches to desired end states or matches to undesired end states. A 3rd study asked ideal versus ought discrepant Ss to select among alternative strategies for friendship. The results suggest that a concern with approach is greater for ideal than ought self-regulation, whereas a concern with avoidance is greater for ought than ideal self-regulation. PMID- 8195987 TI - Social comparison and affiliation under threat: going beyond the affiliate-choice paradigm. AB - This study examined the emotional similarity hypothesis--a derivation from social comparison theory, which predicts that increasing fear should lead to greater affiliation with someone who is awaiting the same threat (and who therefore is of relatively similar emotional status) relative to someone who has already experienced the threat (and who therefore is of relatively dissimilar emotional status). The results failed to support the emotional similarity hypothesis and in so doing challenged the importance of emotional comparison as a determinant of verbal affiliation under threat. Cognitive clarity concerns instead seemed to account better for the observed effects on verbal affiliation. Supplementary analyses of nonverbal affiliation (facial glances) likewise ran counter to an emotional similarity prediction. Effects of affiliation on anxiety were also examined. Previous conclusions regarding the pattern and causes of affiliation under threat that have relied on the affiliate-choice paradigm are considered. PMID- 8195988 TI - Evidence for universality and cultural variation of differential emotion response patterning. AB - The major controversy concerning psychobiological universality of differential emotion patterning versus cultural relativity of emotional experience is briefly reviewed. Data from a series of cross-cultural questionnaire studies in 37 countries on 5 continents are reported and used to evaluate the respective claims of the proponents in the debate. Results show highly significant main effects and strong effect sizes for the response differences across 7 major emotions (joy, fear, anger, sadness, disgust, shame, and guilt). Profiles of cross-culturally stable differences among the emotions with respect to subjective feeling, physiological symptoms, and expressive behavior are also reported. The empirical evidence is interpreted as supporting theories that postulate both a high degree of universality of differential emotion patterning and important cultural differences in emotion elicitation, regulation, symbolic representation, and social sharing. PMID- 8195989 TI - Person and contextual features of daily stress reactivity: individual differences in relations of undesirable daily events with mood disturbance and chronic pain intensity. AB - We examined the mood-related and pain-related consequences of daily stressors among 74 individuals with rheumatoid arthritis who supplied daily reports for 75 days. Meta-analyses of time series regression coefficients disclosed a significant same-day relation between events and mood but no consistent effects of events on same-day pain, next-day mood, or next-day pain. With distributional characteristics of the daily data controlled, Ss with more active inflammatory disease showed a greater positive relation of events with same-day and next-day pain, those with a recent history of more major life stressors showed a greater positive relation of events with next-day pain, and those with less social support showed a greater positive relation of events with next-day mood disturbance. Implications of these and other findings for theories of stress and adaptation and the methodological challenges of daily experience research are discussed. PMID- 8195990 TI - Coping through emotional approach: problems of conceptualization and confounding. AB - Two studies supported hypotheses that (a) published scales tapping coping through processing and expressing emotion are confounded with psychopathology; (b) previously demonstrated relations between emotional approach coping (EAC) and maladjustment are partially spurious; and (c) EAC, when tapped by items uncontaminated by distress, is beneficial under specific conditions. In Study 1, 194 psychologists rated a majority of published items, but no author-constructed EAC item, as indicative of pathology. Study 2 assessed relations of confounded and unconfounded EAC scales to 171 young adults' adjustment during stressful events. Confounded items evidenced weaker discriminant validity with distress measures than did unconfounded items, and they were weaker predictors of later maladjustment when initial adjustment was controlled than when it was not. Unconfounded EAC predicted improved adjustment for women and poorer adjustment for men over time. PMID- 8195991 TI - Mood-moderating effects of affect intensity on cognition: sometimes euphoria is not beneficial and dysphoria is not detrimental. AB - Affect intensity (AI) is a characteristic of temperament that has been hypothesized to moderate the influence of mood on cognitive processing. To test predictions concerning this interaction, 132 women were divided into groups of high and low AI and received positive, neutral, or negative mood inductions. They then engaged in either a self-generated or didactic learning task, and the effects of mood and AI on recall and recognition performance were assessed. Consistent with predictions, positive mood led to poorer performance for high AI relative to low AI individuals, and negative mood resulted in a converse pattern of outcomes. The results are discussed with reference to implications for the AI construct and mood-induction research. PMID- 8195992 TI - Perceived parental social support and academic achievement: an attachment theory perspective. AB - The study tested the extent to which parental social support predicted college grade point average among undergraduate students. A sample of 418 undergraduates completed the Social Provisions Scale--Parent Form (C.E. Cutrona, 1989) and measures of family conflict and achievement orientation. American College Testing Assessment Program college entrance exam scores (ACT; American College Testing Program, 1986) and grade point average were obtained from the university registrar. Parental social support, especially reassurance of worth, predicted college grade point average when controlling for academic aptitude (ACT scores), family achievement orientation, and family conflict. Support from parents, but not from friends or romantic partners, significantly predicted grade point average. Results are interpreted in the context of adult attachment theory. PMID- 8195993 TI - Sex typing and the social perception of gender stereotypic and nonstereotypic behavior: the uniqueness of feminine males. AB - The social perception of masculine, feminine, androgynous and undifferentiated males was examined. Preadolescent boys (n = 251) were shown a video film portraying a male target playing either a masculine game with boys, a feminine game with girls, a neutral game with boys, or a neutral game with girls and were required to make a variety of inferences about him. All 4 groups made similar cognitive stereotypic inferences that varied in accordance with the gender stereotypic nature of the target's behavior. However, for the affective judgments (e.g., liking the target and wanting to engage in activities with him), the feminine males showed a pattern of inferences that was not only different from other sex role orientations, but often the reverse. The implications of these results for S. L. Bem's gender schema theory (1981) and H. Markus's self schema theory (H. Markus, M. Crane, S. L. Bernstein, & M. Siladi, 1982) are discussed. PMID- 8195994 TI - The role of negative affectivity in the association between attributions and marital satisfaction. AB - Structural equation modeling with latent variables was used to test whether negative affectivity, or the cross-situational tendency to experience and express negative thoughts and feelings, correlates with spouses' attributions for relationship events and accounts for the association between attributions and satisfaction. Eighty married couples completed measures of marital satisfaction, attributions, and negative affectivity. Spouses high in negative affectivity tended to make maladaptive attributions, but spouses' attributions were unrelated to the level of negative affectivity reported by the partner. Attributions and marital satisfaction remained associated among husbands and wives after controlling for negative affectivity. These findings clarify the link between attributions and marital satisfaction and raise the possibility that negative affectivity contributes to the attributions that spouses make for negative events in marriage. PMID- 8195996 TI - Sex-related differences in the bone mineral density of atrophic mandibles. AB - The bone mineral content in a standardized site was measured in 25 edentulous mandibles with dual-photon absorptiometry. The results of the bone mineral content examinations demonstrated a significant difference between the sexes. With advancing age of the subjects, the values measured in the men's mandibles tended to increase slightly, whereas those in the women's mandibles tended to decrease. As a functional adaptation to preserve the stability of the male atrophic mandible, the amount of inner cortical bone is increased. Explanations for this observation are discussed. That the mandibles of men and women change differently with increasing age should be considered in routine examinations, because osteoporosis may be regarded as a cofactor of residual ridge resorption in women. PMID- 8195995 TI - In vivo microleakage of luting cements for cast crowns. AB - Standardized tooth preparations were completed on previously intact human molars in vivo, and castings were made with a precious metal ceramic alloy by conventional techniques. The castings were randomly assigned to the following luting agents: zinc phosphate, composite resin-glass ionomer hybrid, and a composite resin-glass ionomer hybrid with a dentinal bonding agent and were cemented in a standardized manner to periodontally compromised molars. After 6 months the teeth were carefully extracted, stained, embedded, and sectioned, and the in vivo microleakage was measured. ANOVA disclosed significant differences between groups, and a multiple comparisons test revealed that the zinc phosphate group leaked significantly more than other cement groups. PMID- 8195997 TI - Removable partial dentures without rests. AB - Ever since Bonwill recommended the use of rests on removable partial dentures in 1899, rests have been universally considered inviolate and have gone unchallenged and untested. The author claims that removable partial dentures without rests may not cause the adverse conditions usually predicted, such as gingival stripping, gingival inflammation, mutilated residual ridges, or extensive and rapid resorption of the alveolar ridges. In removable partial dentures made by the author for several patients, the residual ridge remained stable and in physiologic equilibrium when rests were not used. A history of the long-term effect on patients wearing partial dentures with and without rests is presented. PMID- 8195998 TI - Technique to restore unfavorably inclined implants. AB - Unfavorable inclination of implants is a common problem that may compromise esthetics, phonetics, and function of the implant-supported fixed prosthesis. Several methods have been reported to compensate for malaligned implants; however, most techniques are complicated and expensive. A technique that combines a custom abutment from a hexed UCLA-type plastic burn-out pattern and a manually threaded setscrew hole is a relatively inexpensive and uncomplicated approach to eliminate problems caused by unfavorable implant inclination. This article describes the procedures for fabrication of an implant-supported fixed prosthesis with the use of this technique. PMID- 8195999 TI - Development of implant soft tissue emergence profile: a technique. AB - Despite successful osseointegration of dental implants, patients can be dissatisfied with the definitive restoration because of a poor esthetic result. An esthetic implant restoration depends on correct implant placement and a well designed and fabricated prosthesis that includes the prosthetic teeth and the surrounding whether it is acrylic resin or soft tissue. This article describes a technique to help predict, develop, and evaluate implant prostheses and their soft tissue contours at the provisional restoration stage. This technique records the planned and subsequently proven contours, which are then used to guide fabrication of the final prosthesis and produce a predictable esthetic result. PMID- 8196000 TI - The mandibular subperiosteal implant denture: a prospective survival study. AB - Follow-up, maintenance, and treatment of complications of 81 mandibular subperiosteal implants placed at the University of Southern California Advanced Prosthodontic Clinic were recorded for periods up to 21 years. Few patients were lost to follow-up, but a significant number of patients died before termination of the study. A 10-year survival rate of 79% was calculated for 63 patients, and a 15-year survival rate of 60% was calculated for 34 patients. It was found that subperiosteal implants have a low long-term survival rate, and the rate of loss of subperiosteal implants increases over time without reaching a steady state. However, subperiosteal implant therapy did provide function for patients who otherwise could not use dentures. PMID- 8196001 TI - Implant-supported prostheses for treatment of adults with cleft palate. AB - Six adult patients with cleft palate, ranging in age from 47 to 78 years, were treated with self-tapping titanium implants. Twenty-three implants, 7 to 15 mm in length, were placed. Of these, one (4%) was 7 mm, eight (35%) were 10 mm, nine (39%) were 13 mm, and five (22%) were 15 mm. Time between stage I and stage II implant surgeries was 5 to 14 months, averaging 8.3 months. Time from stage II surgery to the present is 1.5 to 5 years, averaging 3 years. Of the 23 implants placed, 21 (91%) achieved osseointegration. One (4%) implant was not used prosthetically. Two (9%) 10 mm implants failed to integrate in one patient. All patients were treated with a maxillary complete denture or overdenture. Five (83%) required the addition of a pharyngeal section for speech enhancement. PMID- 8196002 TI - Physical properties of three maxillofacial materials as a function of accelerated aging. AB - This study compares the tensile strength, elongation, Shore-A hardness, and tear resistance of three silicone maxillofacial materials before and after aging to provide comparative data for evaluation of new or experimental elastomers. The materials evaluated were MDX-4-4210, Factor II (A-2186), and Cosmesil. Tests were conducted 24 hours after specimen preparation and were repeated after aging for 900 hours in a Weather-Ometer device. Five samples were made for each material under all test conditions. After testing, mean values were calculated for all materials under all test conditions and were compared by two-way analysis of variance and Tukey intervals at p < or = 0.05. PMID- 8196003 TI - Variation of condylar asymmetry with age in edentulous patients with a craniomandibular disorder of myogenous origin. AB - The effect of age on condylar asymmetry in dentate patients has already been investigated and a clear relationship between these two variables was established both for a group with an arthrogenous origin and with myogenous origin of pain. In this study, the mean asymmetry index for an edentulous group of patients with a craniomandibular disorder of myogenous origin was found to be 12.55%, less than that for both dentate groups. There appeared to be no correlation between age and the asymmetry index in this group, suggesting that different mechanisms may be at work in the development of these disorders. PMID- 8196004 TI - Irreversible hydrocolloids: a comparison of antimicrobial efficacy. AB - The surface antimicrobial efficacy of four irreversible hydrocolloid materials against two common oral bacteria, Lactobacillus and Streptococcus mutans, was evaluated. Twelve reversible hydrocolloid (agar) plates for each bacteria were used. Five wells, 1 cm in diameter by 5 ml in depth, were punched into each plate that contained a known concentration of bacteria. An equal-sized but different type of irreversible hydrocolloid plug was placed into each of four wells. The fifth (center) well contained chlorhexidine (Peridex) as a positive control agent. Results indicated that the irreversible hydrocolloids Coe Hydrophilic Gel (CHG) with chlorhexidine and Jeltrate Plus with quaternary ammonium were both as effective as the positive control agent in reducing surface growth of the bacteria studied. The use of antimicrobial irreversible hydrocolloids thus may aid in reducing operatory to laboratory cross-contamination. PMID- 8196005 TI - An in vitro study of a surface wetting agent for addition reaction silicone impressions. AB - The aims of this study were to determine whether the use of a topical surfactant (Hydrosystem) reduced the number of air bubbles visible on the surface of polyvinyl siloxane impressions and stone dies. The impressions exhibited a mean of 1.4 +/- 2.1 bubbles when Hydrosystem wetting agent was used, which was significantly less (p < 0.001) than when it was not used (mean 5.5 +/- 4.7 bubbles). Dies prepared with Hydrosystem surfactant contained a mean of 0.4 +/- 0.8 bubbles, which was significantly (p < 0.001) less than when Wax-Mate surface agent was used (mean 3.5 +/- 5.2 bubbles). In conclusion, in vitro use of Hydrosystem surfactant reduced the number of air bubbles on the surface of silicone impressions and stone dies. PMID- 8196006 TI - Bond strengths between elastomeric impression materials and disinfected preliminary impressions. AB - Bond strengths between disinfected putty impressions and subsequent wash applications were determined in specimens made to simulate clinically an interrupted two-step impression technique. The effect of a disinfectant on the bond strength between a disinfected wash impression and a subsequent wash application was also evaluated to simulate perfecting a disinfected final impression clinically. Vinyl polysiloxane (putty or wash) and polyether (wash only) impression materials were placed in perforated metal cylinders, allowed to set, and dipped in an iodine or glutaraldehyde disinfectant. Wash material was then applied to the disinfected material by use of another metal cylinder and allowed to set before the specimen was tested in tensile mode. Significant decreases in bond strengths were found in both clinical simulations but were limited to specific impression material and disinfectant combinations. PMID- 8196007 TI - Differential accuracy of elastomeric recording materials and associated weight change. AB - Six interocclusal recording materials: COE Bite Creme, Blu-Mousse, Correct Bite, Blue Velvet, Memosil C.D. and Ramitec brands, were studied for evaluation of their dimensional stability and associated weight change. The materials were divided into six groups of 10 samples and tested between metal dental casts on the hydroptic test and measurement system. Dimensional changes among the materials were not significantly different. Weight changes among materials were significantly different but did not exceed 0.1%. All 6 brands were highly accurate and dimensionally stable. PMID- 8196008 TI - Morphologic aspects of the resin-dentin interdiffusion zone with five different dentin adhesive systems tested in vivo. AB - The new generation of enamel dentin adhesive materials provides removal of the smear layer, inducing structural changes in the dentinal surface and creating a retentive interdiffusion zone or hybrid layer between the two substrates. Some studies have demonstrated hybrid layer formation in in vitro samples, but few articles have described it in in vivo specimens. The hybrid layer forms in peritubular and intertubular treated dentin and improves adhesion between tooth surface and adhesive resins. This in vivo study investigated the formation of a hybrid layer by use of five different enamel dentin adhesive systems. The dentin adhesives systems were tested on flat dentin preparations made on vestibular surfaces of periodontally compromised teeth. The sample teeth were extracted immediately after the resin was cured. Half of the samples were used to visualize the hybrid layer and the other half to observe the morphology of the resin tags by use of scanning electron microscopy. All the tested products formed a hybrid layer. In many areas of samples of Gluma 2000, Scotchbond Multipurpose, All Bond 2, and Super Bond D Liner systems, characteristic reverse cone-shaped tags were visible. Resin tags produced by Clearfil Liner Bond adhesive were narrower at the apertures of tubules than those of the other four adhesive materials. Morphology of the hybrid layer and of the resin tags of these samples were similar to in vitro samples observed in other studies. PMID- 8196009 TI - Composite denture teeth made on a removable partial metal framework. AB - Most denture teeth and denture bases are made of polymethyl methacrylate, which does not chemically bond with a metal framework. The absence of a chemical bond leads to weak retention and high microleakage between the resin and metal interface. With a 4-META bonding agent, a chemical bond that increases retention and decreases microleakage can be created between the composite and the metal interface. This article describes a method for making composite denture teeth with a 4-META bonding agent. It can be done without costly equipment and can also be used to repair acrylic resin denture teeth. PMID- 8196010 TI - Simplified procedure for making gold occlusal surfaces on denture teeth. AB - The procedure described is used to reproduce, in gold, the occlusal morphology of complete and removable partial denture teeth or those of an implant-supported prosthesis. The gold occlusal surfaces are made after all adjustments are completed and the occlusion is harmonious. An acrylic resin strut reinforces the wax patterns, and a reline jig is used to accurately stamp out the occlusal anatomy in wax. Careful adherence to the step-by-step procedure is required to achieve an excellent result. PMID- 8196011 TI - Combination stone and resilient material for removable partial denture remount cast described and compared with two other remount cast procedures. AB - A procedure for making a combination remount cast of stone and elastomeric material for removable partial dentures is described in detail and is compared quantitatively with two other methods for making remount casts for removable partial dentures. This method does not require blocking out the undercuts in the denture base or around the clasps. PMID- 8196012 TI - A one-appointment procedure for cast post and core restorations. AB - An accelerated method of using a light-cured acrylic resin and rapid burnout for casting a direct-pattern post and core restoration is presented. Light-cured acrylic resins are an alternative to chemically cured acrylic resins or indirect patterns formed from an elastomeric impression. The procedure can eliminate an appointment for the patient in the fabrication of the post and core restoration and can be completed in most dental offices with minimal laboratory facilities. Chair-side time is saved because of the elimination of one provisional restoration when two are usually required. Laboratory time is also saved because of the decrease in investment setting and burnout time. PMID- 8196013 TI - Shear strength of composite bonded porcelain-to-porcelain in a new repair system. AB - This study assesses the repair procedure for porcelain fracture and involves fitting and bonding a porcelain material over the original damaged crown. To simulate the situation, a test sample was designed to simulate composite bonded porcelain-to-porcelain. A total of 120 samples was prepared and the shear bond strengths were tested. Three composite resins, two porcelain combinations, and two storage-time intervals were used. Significant differences were found among the three types of composite resins. Porcelain combinations did not affect the results. Furthermore, the mean bond strength was higher at 45-day storage than at 90 days. PMID- 8196014 TI - A new instrument for placement of self-threading retention pins. PMID- 8196015 TI - Grief resolution: facilitating self-transcendence in the bereaved. AB - 1. The clinical nurse specialist (CNS) can help individuals to resolve grief that stems from personal loss and death, and encourage activities that will assist highly motivated individuals to achieve self-transcendence. 2. Self-transcendence is the ability to extend one's self beyond personal concerns and reach out to others without losing one's sense of self. The process of self-transcendence results in broader perspectives, purposes, and activities in one's life. Self transcendent acts of giving to and/or sharing with others leads to a sense of connectedness with others, one's surroundings, and God. 3. Ultimately, the CNS encourages the bereaved person to participate in a grief resolution support group. By sharing openly and actively participating in the group process, the bereaved person learns coping skills that facilitate grief resolution and encourage the development of self-transcendency. PMID- 8196016 TI - Cost-effectiveness and quality of care provided by clinical nurse specialists. AB - Clinical nurse specialists in psychiatric-mental health nursing provide primary mental health services to prevent and treat minor mental illnesses and collaborate with physicians to provide mental health services to those with complex mental and/or physical illnesses. CNSs practice in a wide range of settings and in rural and urban areas. Eliminating bureaucratic, attitudinal, legal, and insurance barriers to the services of CNSs in psychiatric mental health nursing can improve access, lower costs, and enhance the quality of mental health delivery systems. Nurses can eliminate some of these barriers. Within bureaucratic organizations, such as hospitals and clinics, nurses can document problems and experiment with collaborative models of practice that make full use of their skills. Nurses must be active participants, including taking on leadership roles, in committees that address changes in patient and health care policies in their organizations. Changing attitudes by educating the public--as well as other health care providers and politicians--about the roles and credentials of nurses is instrumental to removing barriers. Brochures about the roles and credentials of nurses can be prepared and disseminated to patients, civic organizations, other health care providers, and politicians. Nurses should never miss an opportunity to address one of these groups! Demonstrating excellence in nursing practice leaves a lasting impression on patients and other health team members. Implementing innovative approaches to care based on current literature in nursing and related areas is an advanced practice expectation. Further documentation of the impact on cost and quality of care by nurse providers is necessary. Legal and insurance barriers are the most resistant to change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196017 TI - The ethical considerations of managed care in mental health treatment. AB - 1. Managed care as a cost-cutting technique is becoming increasingly prevalent; one reason for its growth is the increasing number of people covered by health maintenance organizations and preferred provider organizations. 2. Ethical areas of concern raised by managed care include restrictions on patient autonomy of choice of treatment and treatment site; relationship between the nurse as a managed care agent and the patient; patient responsibility in treatment decisions made through managed care; and denial, curtailment, or alteration of access to treatment based on compliance. 3. Managed care is a tool to conserve and equitably distribute care resources. To be certain that managed care performs this function equitably, the profession must continue to examine managed care in the light of biomedical ethics. PMID- 8196018 TI - Depression in African-American women. AB - Depression is an increasing problem for African-American women. These women are experiencing role changes and additional stressors. Depressed African-American women may perceive themselves as being devalued within American society and may have fewer support systems to buffer stressful conditions (Carrington, 1980). Depressive symptoms may escalate into clinical depression, which can erode quality of life for African-American women. Psychiatric mental health nurses can be instrumental in developing protocols and individualized interventions that respond to the psychological and physical needs of their depressed clients and promote an improved quality of life. PMID- 8196019 TI - Tacrine: a pharmacological approach to Alzheimer's disease. AB - Overall, studies of the effect of tacrine on the cognitive symptoms of AD are inconclusive. Small (1992) gave some insight into this variability of results by stressing that different research methods can generate different outcomes. Small also pointed out that there is an inherent weakness in the Mini Mental State Examination (MMSE)--a tool used in most, if not all, AD studies. The MMSE is not sensitive to subtle and real changes in mental function. Regardless of the inconclusiveness of these studies, research must continue in order to tease out the variables contributing to clinically significant gains found in some studies. Anecdotal observations, combined with the previously summarized clinical trials, indicate that a subgroup of AD patients may hope to benefit from tacrine. At a geriatric clinic with which the author is associated, prospective patients and their families are told that tacrine helps about 10% to 20% of those who take it. Further, they are instructed that tacrine seems to be most helpful if given early in the disease process and that it is relatively expensive. Treatment with tacrine costs about $1,000 to $1,500 per year (Anderson, 1993). The maximum dose of tacrine is 120 mg per day, and there is a relatively high incidence of side effects. The most serious side effect of tacrine is liver toxicity, which occurs in up to 30% of the patients taking this drug. Elevations in serum aminotransferase levels occur with the same frequency and therefore must be closely monitored. Additionally, 20% of patients taking tacrine develop nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196020 TI - The physical and mental health of women caregivers of older adults. PMID- 8196021 TI - Battling schizophrenia: my fight for dignity. PMID- 8196022 TI - Telephone counseling interventions with caregivers of elders. AB - 1. The use of the telephone in therapy has been documented in the care of disabled persons and persons with cancer and can be used with other populations. Telephone counseling is a feasible addition to the repertoire of assistance programs available. 2. The use of telephone counseling as an in-home intervention addresses some of the major limitations of out-of-home interventions, such as travel, making arrangements for an alternate caregiver, and worry due to absence from the care recipient. Telephone counseling also provides a means of reaching isolated or rural caregivers who have few or no available services. Telephone care can be a cost-effective, time efficient, and culturally acceptable intervention. 3. Telephone counseling has a potential value with caregivers comparable to the outcomes derived from pioneer mental health services, such as crisis intervention, suicide hot lines, and information and referral services. Nurses and other health care workers are encouraged to respond to the opportunities and challenges, as well as the promises, of telephone counseling intervention. PMID- 8196023 TI - Treatment of arrow wounds by nineteenth century USA Army surgeons. PMID- 8196024 TI - The portrayal of the physician in non-medical literature--versatile scholar or ignorant boor? PMID- 8196025 TI - Osteoma cutis as a sequela of acne. PMID- 8196026 TI - Use of two stage keratinocyte-dermal grafting to treat the separation site in conjoined twins. PMID- 8196027 TI - Hypoglycaemia and Golytely in distal intestinal obstruction syndrome. PMID- 8196028 TI - Primary pigmented nodular adrenocortical dysplasia: a rare form of a rare disorder. PMID- 8196029 TI - Antiplatelet therapy following coronary artery surgery. PMID- 8196030 TI - Empyema thoracis in AIDS. PMID- 8196031 TI - The genius of disease. 4. Culture dependent illness: Keats, Mozart and Margaret Atwood. PMID- 8196032 TI - Outcome assessment of endoscopic sinus surgery. PMID- 8196033 TI - APACHE II scoring system on a general intensive care unit: audit of daily APACHE II scores and 6-month survival of 691 patients admitted to a general intensive care unit between May 1990 and December 1991. AB - In this paper we present a detailed analysis of the use of the APACHE II (acute physiological and chronic health evaluation) scoring system on all of the patients admitted to the general intensive care unit at the Bristol Royal Infirmary over a 20-month period. The 6-month survival of 691 adult medical and surgical patients following intensive care was recorded and this data was analysed with admission and daily APACHE II scores using a relational database. Our data confirms the relationship between admission APACHE II scores and outcome, with mean scores decreasing as duration of survival increases. We also demonstrate that the best day one scores are approximately 50% less than the admission score, irrespective of outcome, indicating the benefit of intensive care. By contrast, however, the scores on day one have either not improved or have worsened since admission, reflecting the importance of the pre-morbid health status of the patient in determining outcome from intensive care. PMID- 8196034 TI - A pilot study into the prevalence of ophthalmic disease in the Indian population of Southall. AB - A pilot study was carried out to determine the prevalence of ophthalmic disease in the Indian community of Southall and to ascertain the best methods applicable for a larger formal study. Three sites were chosen for the study, a Sikh gurdwara, a mosque and a Hindu temple. The subjects were volunteers aged 30 years and over who had visited the appropriate place of worship at least twice in the previous month. A total of 184 subjects were examined. The prevalence of blindness was 2.7% by the World Health Organization (WHO) criteria, while 9.8% had uniocular blindness. The prevalence of glaucoma and ocular hypertension was 2.7% and 7%, respectively. Of the 184 subjects examined, 58% had cataract and 3.8% had age-related maculopathy. The prevalence of visually disabling trachomatous eye disease was 9.7%. The prevalence of diabetes mellitus was 17.9%, and that of hypertension 22.8%. This small study suggests that people with origins from the Indian subcontinent have a higher prevalence of ophthalmic disease than the Caucasian population. PMID- 8196035 TI - What's so special about being 65? The challenge facing eldercare departments. AB - There is no abrupt change in physiology, pathology or pharmacology occurring at or around the age of 65 years. There is some evidence of a change in the effect of illness, and of the prevalence of disability with advancing age. However, these changes are individual and gradual, and more associated with passing 75-80 years rather than 65. The main change occurring in the seventh decade arises from retirement from paid employment, and is therefore financial. Hence, in contrast to personal financial support, Health and Social Services departments would be ill advised to use the age of 65 as a threshold. Age-related admission policies may perpetuate ageism, and needs-related policies may therefore be preferable. The challenge facing departments of geriatric medicine and psychiatry is to present their services attractively to patients, carers and purchasers, who need to recognize the rationale for the purchase of these forms of care, with reference not only to benefit to patients, but also to their informal carers. PMID- 8196036 TI - Resource implications of head injuries on an acute surgical unit. AB - Head injuries are expensive and demanding in terms of resources. In the UK, most are cared for outside neurosurgical centres. In the absence of specialist rehabilitation services, patients with on-going disability add to those admitted for observation and treatment on acute surgical wards. We audited the workload pattern and financial implications related to head injuries on a general surgical unit in a central London teaching hospital. Data collected prospectively at the time of admission and derived from departmental computerized information systems included clinical outcome, hospital stay and its relationship to severity of injury and other factors. Ward, departmental (accident and emergency (A & E), intensive therapy unit (ITU), radiology, and theatre) and neurosurgical referral costs were derived. Long-term social and rehabilitation costs were not calculated. Over a 6 month period 899 patients with head injuries were treated in the A & E department, of whom 156 were admitted. Of the admitted patients 68% were classified as minor; 22% as moderate; and 10% as severe head injuries. Fifty one per cent of adult admissions were intoxicated by alcohol. Prolonged hospital stay was related to age, severity of head injury, mechanism of injury, associated injuries and preexisting neuropsychiatric conditions (including alcoholism). Six patients died. The direct cost of these head injuries patients was estimated at 173,500 pounds, during which time they occupied 7.6% of our unit's adult inpatient capacity. Twenty-four hour observation of 76 patients with minor head injuries contributed 9700 pounds (5.6%) to this figure. Associated extracranial injuries cost a further 46,500 pounds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196037 TI - The contribution of clinical genetics to molecular genetics in psychiatry. PMID- 8196038 TI - 60 years of chemical carcinogens: Sir Ernest Kennaway in retirement. AB - 1992 marks the sixtieth anniversary of the publication of the first paper on the production of cancer by pure hydrocarbons, by the team at the Chester Beatty Research Institute headed by Professor Kennaway. Studies on polycyclic aromatic hydrocarbons and other chemical carcinogens continued to thrive under his leadership in succeeding years at the Chester Beatty and beyond, into his 'retirement' in 1946. He played a key role in stimulating research on factors contributing to the epidemic of lung cancer that became apparent by then, and with the support of the Medical Research Council (MRC) and other organizations he directed a small team working on analytical and epidemiological studies in a makeshift laboratory at St Bartholomew's Hospital. Published work included the identification and determination of benzo(a)pyrene in domestic soot, urban air pollution, motor vehicle exhausts and cigarette smoke, also arsenic in urban air and cigarette smoke, radon in indoor air and carbon deposits in human lungs. Such studies have been pursued in other laboratories around the world since then, and many of the lines of enquiry are traceable back to the pioneering work of the team at the Chester Beatty 60 years ago. PMID- 8196039 TI - Did Edward V suffer from histiocytosis X? PMID- 8196040 TI - Crystal and molecular structure of barley alpha-amylase. AB - The three-dimensional structure of barley malt alpha-amylase (isoform AMY2-2) was determined by multiple isomorphous replacement using three heavy-atom derivatives and solvent flattening. The model was refined using a combination of simulated annealing and conventional restrained least-squares crystallographic refinement to an R-factor of 0.153 based on 18,303 independent reflections with F(o) > sigma(F(o)) between 10 and 2.8 A resolution, with root-mean-square deviations of 0.016 A and 3.3 degrees from ideal bond lengths and bond angles, respectively. The final model consists of 403 amino acid residues, three calcium ions and 153 water molecules. The polypeptide chain folds into three domains: a central domain forming a (beta alpha)8-barrel of 286 residues, with a protruding irregular structured loop domain of 64 residues (domain B) connecting strand beta 3 and helix alpha 3 of the barrel, and a C-terminal domain of 53 residues forming a five stranded anti-parallel beta-sheet. Unlike the previously known alpha-amylase structures, AMY2-2 contains three Ca2+ binding sites co-ordinated by seven or eight oxygen atoms from carboxylate groups, main-chain carbonyl atoms and water molecules, all calcium ions being bound to domain B and therefore essential for the structural integrity of that domain. Two of the Ca2+ sites are located only 7.0 A apart with one Asp residue serving as ligand for both. One Ca2+ site located at about 20 A from the other two was found to be exchangeable with Eu3+. By homology with other alpha-amylases, some important active site residues are identified as Asp179, Glu204 and Asp289, and are situated at the C-terminal end of the central beta-barrel. A starch granule binding site, previously identified as Trp276 and Trp277, is situated on alpha-helix 6 in the central (beta alpha)8 barrel, at the surface of the enzyme. This binding site region is associated with a considerable disruption of the (beta alpha)8-barrel 8-fold symmetry. PMID- 8196041 TI - X-ray structure at 1.55 A of toxin gamma, a cardiotoxin from Naja nigricollis venom. Crystal packing reveals a model for insertion into membranes. AB - The crystal structure of toxin gamma from Naja nigricollis has been solved and refined to 1.55 A resolution. The final R-factor, computed with all X-ray data available, is 17.9%. The three-dimensional structure is characterized by a core formed by two beta-sheets organized in three extended loops. It is similar to that of cardiotoxin V4II from Naja mossambica mossambica, with the exception of the hydrophobic loop I. The flexibility and variability of the loops contrast sharply with the rigidity of the molecular core and its high degree of structural conservation among the cardiotoxin family. The most flexible loop II adopts different conformations in the three monomers forming the crystal asymmetric unit. These monomers form a trimer around an approximate 3-fold axis, with conserved hydrophobic side-chains on the outside and hydrophilic residues in the central channel or involved in interactions with the other molecules. The trimer thus resembles a membrane protein with a central channel that could allow the passage of small ions. It is proposed as a model for the insertion of cardiotoxin into a membrane. PMID- 8196042 TI - Solution structure and dynamics of PEC-60, a protein of the Kazal type inhibitor family, determined by nuclear magnetic resonance spectroscopy. AB - The three-dimensional solution structure of porcine PEC-60, a 60 amino acid residue protein of the Kazal type family of proteinase inhibitors, was determined by nuclear magnetic resonance (NMR) spectroscopy. The structure determination is based on nearly complete 1H, 13C and 15N resonance assignments including stereospecific 1H resonance assignments for 40 pairs of methylene protons and isopropyl methyl groups. The stereospecific resonance assignments of the beta protons were supported by heteronuclear long-range correlation experiments recorded at natural 13C and 15N isotopic abundances. A group of 20 conformers were calculated using the experimentally derived NMR constraints with the program DIANA, and energy-minimized in a 4 A water shell using the program OPAL. The average of the root-mean-square deviations relative to the mean structure of the 20 conformers selected to represent the solution structure of PEC-60 is 0.55 A for the backbone atoms of residues 6 to 10 and 24 to 60. Disordered conformations are observed for the amino-terminal pentapeptide and the polypeptide segment containing residues 11 to 23. The NMR structure confirms the structural similarity of PEC-60 to the Kazal type family of proteinase inhibitors which had been previously suggested on the basis of amino acid homology. The well-defined part of PEC-60 contains a short three-stranded anti-parallel beta-sheet involving the residues 27 to 29, 33 to 35 and 53 to 56 with a beta-bulge at residue 55, a type I turn comprising residues 29 to 32, and an alpha-helix involving the residues 37 to 48. T1(13C) relaxation measurements of the alpha-carbons and linewidth measurements of the amide proton signals indicate substantially increased mobility on the pico- to nanosecond time-scale for the amino-terminal pentapeptide as well as within the loop comprising residues 11 to 23. The structure of PEC-60 is compared to the X-ray crystal structures of homologous Kazal type proteinase inhibitors and the dynamic properties of PEC-60 are discussed with respect to the observed lack of any substantial trypsin inhibiting activity. PMID- 8196043 TI - Analysis of the N-terminal leucine heptad and hexad repeats of sigma 54. AB - In order to assess the role of leucine repeat motifs within bacterial protein sigma 54, a series of point mutants were introduced into the many leucine residues near the N terminus. Functional assays in vivo showed that the leucine residues that comprise the previously identified heptad repeat motif are selectively important for function. These heptad leucine residues are critical for mRNA production and also for recognition of the -12 promoter element. An internal proline substitution destroys the function of the heptad repeat region, suggesting a possible alpha-helical structure. Mutants with changes in the distal part of this N-terminal region show the interesting property of allowing nearly full levels of open complex formation, while nonetheless reducing the level of mRNA transcripts produced. All of the above-mentioned properties differ from those exhibited by mutating the interdigitated glutamine residues, which were previously found to be closely involved in the DNA melting reaction. The collection of data suggests that the N-terminal region contains overlapping functional motifs, hydrophobic heptad and glutamine-rich, which together appear to constitute the activation domain of sigma 54. PMID- 8196044 TI - Crystallization and preliminary X-ray analysis of an anti-staphylococcal nuclease staphylococcal nuclease complex and of a second anti-staphylococcal nuclease antibody. AB - The Fab fragments of several monoclonal antibodies that bind Staphylococcal nuclease have been screened for crystallization conditions. Two of these, N10 and N25, have been crystallized in forms suitable for X-ray structural analysis. The anti-Staphylococcal nuclease antibody complex N10 Fab-nuclease crystallizes with symmetry consistent with space group C2 and cell parameters of a = 234.7 A; b = 43.5 A; c = 74.4 A; beta = 106.4 degrees. A second anti-Staphylococcal nuclease antibody, N25, although crystallized starting with the Fab-nuclease complex, apparently crystallizes as uncomplexed N25 Fab with symmetry consistent with space group P3(1)21 (or its enantiomorph P3(2)21) and cell parameters of a = b = 80.9 A; c = 138.4 A. PMID- 8196045 TI - Crystallization and preliminary X-ray diffraction studies of nitric oxide reductase cytochrome P450nor from Fusarium oxysporum. AB - Crystals of cytochrome P450nor (P450nor), nitric oxide reductase from Fusarium oxysporum, were obtained by means of the hanging-drop vapour diffusion technique in the presence of 1.88 M ammonium sulphate (pH 7.2). They belong to the monoclinic space group P2(1), with unit cell dimensions of a = 74.7 A, b = 86.7 A, c = 62.0 A and beta = 97 degrees. There are two molecules of P450nor in the asymmetric unit. The crystal diffracted to beyond 2.5 A resolution and is suitable for X-ray crystallographic study. PMID- 8196046 TI - The linkage change of a knotting reaction catalysed by Tn3 resolvase. AB - Tn3 resolvase catalyses recombination between a pair of identical res sites, directly repeated on a supercoiled plasmid molecule. The normal in vitro product is a two-noded catenane. A plasmid with a single base substitution at one res site is converted to non-recombinant knots by resolvase; the first major product is a four-noded knot. The linkage change, delta Lk, on formation of the four noded knot is +4. The formation of the observed knots from the mutant substrate, and this value of delta Lk were predicted by and in agreement with a "simple rotation" model for catalysis of strand exchange by resolvase. A number of alternative mechanisms for knotting by resolvase are inconsistent with the observed topological changes. PMID- 8196047 TI - Adenine.methylthymine base-pairs enhance non-uniformity in DNA helices. AB - Nitroso compounds are known to induce mutations and cancer. Here we study the effect of methylation of O4 of thymine by nitroso compounds on the structure and dynamics of DNA helices. Four dodecamers, for which there exist experimental data obtained by NMR techniques, are studied using very long (approximately 1 ns) molecular dynamics simulations. The conformations obtained are in good agreement with the NMR data. A statistical analysis indicates that DNA in solution adopts conformations which are intermediate between those of the ideal DNA families, such as A and B-DNA. Also, the structures obtained in these molecular dynamics simulations possess a greater degree of non-uniformity than the crystal structures. Most importantly, the helices containing adenine.methylthymine base pairs show a further enhancement in non-uniformity. A biological role for the enhanced nonuniformity is suggested. PMID- 8196049 TI - The crystal structure of C-C-A-T-T-A-A-T-G-G. Implications for bending of B-DNA at T-A steps. AB - The single-crystal X-ray analysis of trigonal C-C-A-T-T-A-A-T-G-G, and its comparison with orthorhombic C-G-A-T-T-A-A-T-C-G, have shown that the A-T-T-A-A-T sequence has limited polymorphism under the influence of packing forces from neighboring molecules in the crystal. The T-A step is intrinsically variable. It is not inconsistent with a large propeller twist, a narrow minor groove, and a single spine of hydration, as has sometimes been claimed on theoretical grounds. The T-A step does show a persistent positive roll, in a direction that compresses the major groove, and this may be a significant factor in macroscopic DNA curvature induced by phased A-tracts. A-tracts, as understood in this paper, include A-A and A-T steps, but not the T-A step, which is disruptive. Three conclusions regarding A-tract-induced curvature can be drawn from this and other X-ray crystal structure analyses, and from key gel retardation experiments: (1) The A-tract bending model is disqualified on two grounds: (i) tilt-wedge bending within A-tracts is incompatible with the observed direction of curvature; (ii) roll-wedge bending within A-tracts is contradicted by every crystal structure analysis, and is inconsistent with gel retardation results for (G-C-A-A-A-A-T-T-T T)n and for (A-A-A-A-A-T-T-T-T-T)n. (2) The junction bend model is contradicted by crystallography because: (i) the inclination of base-pairs does not change between A-tract and non-A-tract regions of helix; and (ii) the observed bends at GC/AT junctions are roll-wedge bends, not tilt-wedge as the junction bend model demands. (3) The non-A-tract bending model is consistent with both gel retardation data and with X-ray crystallography, and must be regarded as the only consistent model for A-tract bending. PMID- 8196048 TI - In vitro assembly of repertoires of antibody chains on the surface of phage by renaturation. AB - Antibodies can be made from repertoires of associated heavy and light chains displayed on the surface of bacteriophage, and are readily diversified by random point mutation or by chain shuffling. To make extensive variations around the "core" antigen binding contacts of a crystallographically solved mouse antibody NQ10/12.5 (gamma l, kappa), the NQ10 light chain was assembled in vitro with a repertoire of about 10(7) human heavy chains displayed on the surface of phage, and selected by binding to hapten. An antibody with a much improved affinity was isolated from the repertoire (K(a) = 10(9) M-1 compared with 10(8) M-1 for NQ10). The sequence of the human heavy chain (VH-IL) was highly related to NQ10. It conserved the same folds for the H1, H2 and H3 loops, six of the seven contact residues for hapten, and also a phOx binding motif (Asp-X-Gly-X-X) in the H3 loop. It appears that the new heavy chain partners for the NQ10 light chain often retain many critical antigen binding features found in the NQ10 heavy chain. PMID- 8196050 TI - Alternative native flap conformation revealed by 2.3 A resolution structure of SIV proteinase. AB - A large conformational change is observed between HIV-1 proteinase in the ligand free state and in complexes with transition-state inhibitors. Crystal structures of this enzyme have either the flaps open for the native or ligand-free enzyme or the flaps closed for peptidomimetic ligand-bound enzyme. We describe the structure of native recombinant SIV proteinase which like other retroviral proteinases crystallizes as a perfect 2-fold symmetric dimer but in a different crystal packing arrangement. In contrast to HIV-1 PR we show that SIV proteinase in the ligand-free state adopts the closed flaps conformation, demonstrating that ligand binding is not a prerequisite for the closed flaps conformation. The catalytic water was clearly observed between the two aspartates which were not perfectly co-planar, and in this structure the active site cleft is more restricted than for either inhibitor bound or ligand-free HIV-1 proteinase. Accommodation of two bulkier side-chains in the simian enzyme core has resulted in a more exposed N terminus than for HIV-1 PR which we predict could enhance autocatalytic cleavage at the N terminus. PMID- 8196051 TI - Interstitial telomeric repeats within the Arabidopsis thaliana genome. AB - The sequence taAACCCTAa, or telo-box, is found at the same location within all known promoters of plant genes encoding the translation elongation factor EF-1 alpha. An analysis of Arabidopsis DNA sequences available in databases revealed that the sequence AAACCCTAA, corresponding to 1.3 units of the plant telomeric repeat AAACCCT, is over-represented within the Arabidopsis genome. These motifs are found both within the transcribed and the untranscribed genome. The examination of their location in the available sequences as well as in selected and partially sequenced cDNA clones suggest that they are preferentially located in the 5' region of genes. We show that a protein present in both maize and Arabidopsis cellular extracts is able to interact specifically with this motif. The putative functions associated with this sequence are discussed. We propose a model involving the telomerase to explain the spreading of this motif within the genome. PMID- 8196052 TI - Intragenic processing in yeast rRNA is dependent on the 3' external transcribed spacer. AB - The nucleotide sequence of the 3' external transcribed spacer (3' ETS) region in Schizosaccharomyces pombe rDNA was determined to define structural features which mediate the termination of RNA transcription and subsequent rRNA maturation. S1 nuclease protection studies suggest three alternative termination sites and four cleavage sites in the processing of the 3' ETS sequence. Each of the termination sites precedes a "Sal box"-like sequence which has been demonstrated to mediate the termination of rRNA transcription in mammalian cells. A highly conserved extended hairpin structure in the ETS sequence was deleted by PCR-mediated mutagenesis and the mutant rDNA was expressed in vivo to determine its role in rRNA maturation. Despite an efficient expression of the mutant gene, mature 5.8 S or 25 S rRNA was not observed. Labelling kinetics and S1 nuclease protection analyses indicate that the deletion not only fully inhibits the removal of the 3' ETS but also fully inhibits the processive excision of the second internal transcribed spacer (ITS2). Instead, a relatively stable 27 S nRNA precursor remains easily detectable in the whole cell RNA population. The results demonstrate a critical dependence of ITS processing on the 3' ETS raising the possibility that these sequences interact in a common processing domain. PMID- 8196053 TI - A parallel DNA triplex as a model for the intermediate in homologous recombination. AB - Parallel DNA triplexes considered to be putative intermediates in homologous recombination, are studied by means of theoretical conformational analysis. These triplexes are denoted as the R-form DNA. Two types of triplexes are analyzed: extended R-form DNA, modeling the triple standard structure, created transiently in the presence of recombination proteins (e.g. RecA); and collapsed R-form, obtained after deproteinization. These structures are stereochemically possible for any arbitrary sequence and have the following properties: (1) the third, R strand, is parallel to the identical duplex strand and is located in the major groove of the duplex; (2) positions of all four bases in the R-strand are nearly isomorphic; (3) the proposed triplets are consistent with the chemical modification data for deproteinized DNA; we suggest, however, that they are the same in the RecA-DNA complex as well. Since the patterns of charges on each base of the R-strand are strictly complementary to the charges of the homologous Watson-Crick (WC) pair in the major groove, we propose that the selection of the homologous sequence may occur through these complementary electrostatic interactions (electrostatic recognition code). We demonstrate that in the collapsed triplex with a rise of about 3.4 A, the bases from the third R-strand can be inclined and interact with two WC base-pairs simultaneously, which could lead to recognition errors. These mispairings are unlikely in the extended triplex. Therefore, we speculate that a functional role of the extended and underwound DNA structure, transiently formed in the complex with RecA protein, is to obviate such errors and increase the stringency of recognition. In other words, RecA plays the role of a DNA chaperone facilitating the recognition of the single stranded DNA and the duplex. Finally, we show that the proposed isomorphic triplets are conformationally advantageous for strand exchange. PMID- 8196054 TI - OXA1, a Saccharomyces cerevisiae nuclear gene whose sequence is conserved from prokaryotes to eukaryotes controls cytochrome oxidase biogenesis. AB - Yeast cells carrying a mutation in the OXA1 nuclear gene are respiratory deficient and lack cytochrome oxidase activity. We successively examined the different steps in the expression of the mitochondrial genes encoding the cytochrome oxidase subunits and apocytochrome b in strains carrying the oxa1-79 mutation. The ox1-79 strains exhibit a total absence of cytochrome aa3 and a decrease in cytochrome b, even in a strain devoid of mitochondrial introns, in which cox1 and cytb mRNAs normally accumulate. The three mitochondrial-encoded subunits of cytochrome oxidase are still detectable although their amount is reduced, and apocytochrome b is synthesized normally. These results suggest that the OXA1 gene is primary required at a post-translational step in cytochrome oxidase biogenesis, probably at the level of assembly, although the oxa1-79 mutation leads to some pleiotropic secondary defects in earlier steps of mitochondrial gene expression. The OXA1 gene has been cloned, sequenced, and disrupted. The phenotypes of the oxa1::LEU2 and oxa1-79 alleles are similar. Interestingly, the OXA1 gene, located on the yeast chromosome VIII, is adjacent to the gene PET 122, which controls the initiation of cox3 mRNA translation. In addition, the predicted OXA1 protein is homologous to several putative prokaryotic and eukaryotic proteins, suggesting that the function of the OXA1 protein is important for respiration in all living cells. PMID- 8196055 TI - Complex formation between phage phi 29 single-stranded DNA binding protein and DNA. AB - Bacteriophage phi 29 gene 5 encodes a single-stranded DNA (ssDNA) binding protein (SSB) which stimulates viral DNA replication. In the present study, a structural characterization of the complex between ssDNA and the phi 29 SSB was carried out using electron microscopy, band-shift assays and nuclease digestion as well as by monitoring changes in the intrinsic fluorescence of phi 29 SSB upon binding. Phage phi 29 SSB behaves as a monomer in solution and forms complexes with ssDNA which have a homogeneous structure, as if they consist of a continuous array of protein bound to DNA. Interaction of phi 29 SSB with ssDNA leads to a quenching of its tyrosine-dependent intrinsic fluorescence. This fluorescence quenching was directly proportional to the amount of phi 29 SSB bound to the ssDNA and the maximal quenching upon binding was very high (Qmax = 94.6 +/- 3.5%). Direct titration experiments have allowed us to estimate that the stoichiometry (n) of binding to ssDNA was 3.4(+/- 0.3) nucleotides per phi 29 SSB monomer. Both Qmax and n are independent of the salt concentration, suggesting the existence of only one major binding mode. At low salt concentrations, the effective binding constant (Keff = K omega) to poly(dT) was 2.2 x 10(5) M-1, the intrinsic binding constant (K) and the cooperativity parameter (omega) being 4.3 x 10(3) M-1 and 51, respectively. At increasing salt concentrations, the Keff exhibited a small, but significant, decrease. The possible functional significance of the binding parameters of phi 29 SSB during viral DNA replication is discussed. PMID- 8196056 TI - Measuring residue associations in protein structures. Possible implications for protein folding. AB - We propose a number of distance measures between residues in protein structures based on average, minimum and maximum distances of all atom (backbone and side chain) coordinates or with respect to side-chain atom coordinates only. The d1 distance (D1-distance) refers to the average distance between side-chain (backbone and side-chain) atoms of a residue pair in a given structure. The dm distance (Dm-distance) refers to the minimum distance between side-chain atoms (non-trivial minimum distance between all atoms of a residue pair). For each distance measure, averaging and normalizing over representative protein structures, association values and closeness orderings for all amino acid types are determined. The expected associations of side-chain interactions between oppositely charged residues, among hydrophobic residues and of cysteine with cysteine are confirmed. Several surprising associations are observed relative to (1) the aromatic residues tyrosine and tryptophan, but not phenylalanine; (2) multiple histidine residues; (3) asymmetries of arginine versus lysine, aspartate versus glutamate, alanine versus glycine, and asparagine versus glutamine; (4) absence of correlations of alpha-carbon distances with side-chain distances. The all atoms D1-distance attractions are dominated by steric relationships, with glycine and alanine significantly close to all amino acids, whereas large residues are under-associated with all residue types. In contrast, for the closeness ordering corresponding to the minimum side-chain dm-distance, glycine and alanine are among the least associated. However, in the d1-distance alanine is significantly close to all hydrophobic residues with the exception of tryptophan. The dm-distance preferences display a pervasive attraction for tyrosine by almost all residue types, the prominence of tyrosine and tryptophan in cation-aromatic interactions, and the versatility of histidine in functionality. The principal findings suggest a new perspective on the early and intermediate stages of protein folding. PMID- 8196057 TI - Application of a self-consistent mean field theory to predict protein side-chains conformation and estimate their conformational entropy. AB - Understanding the relations between the conformation of the side-chains and the backbone geometry is crucial for structure prediction as well as for homology modelling. To attempt to unravel these rules, we have developed a method which allows us to predict the position of the side-chains from the co-ordinates of the main-chain atoms. This method is based on a rotamer library and refines iteratively a conformational matrix of the side-chains of a protein, CM, such that its current element at each cycle CM (ij) gives the probability that side chain i of the protein adopts the conformation of its possible rotamer j. Each residue feels the average of all possible environments, weighted by their respective probabilities. The method converges in only a few cycles, thereby deserving the name of self consistent mean field method. Using the rotamer with the highest probability in the optimized conformational matrix to define the conformation of the side-chain leads to the result that on average 72% of chi 1, 75% of chi 2 and 62% of chi 1 + 2 are correctly predicted for a set of 30 proteins. Tests with six pairs of homologous proteins have shown that the method is quite successful even when the protein backbone deviates from the correct conformation. The second application of the optimized conformational matrix was to provide estimates of the conformational entropy of the side-chains in the folded state of the protein. The relevance of this entropy is discussed. PMID- 8196058 TI - Erythrina caffra trypsin inhibitor retains its native structure and function after reducing its disulfide bonds. AB - Erythrina trypsin inhibitor (ETI) from the seeds of Erythrina caffra is a high affinity inhibitor of trypsin, chymotrypsin and tissue plasminogen activator. Its 172 amino acid polypeptide chain is stabilized in its compact, native state by two disulfide bonds. In spite of their conservation in all trypsin inhibitors of the soybean trypsin inhibitor (STI-Kunitz) family, their state of oxidation is essential only for protein stability but not for inhibitory function. Reduction/reoxidation of ETI in the presence of glutathione reshuffling buffer (GSH/GSSG; pH 8.3) not only allows the inhibitor to be restored in its native structure, but also does not interfere with its binding affinity; carboxymethylation or carboxamidomethylation of the free thiol groups does not affect K1 significantly (for trypsin (KI)ETIox = 2.3 nM, (KI)ETICM = 1.9 nM; for chymotrypsin (KI)ETIox = 30 microM, (KI)ETICM = 25 microM). The two cystine cross bridges in the native ETI lead to enhanced stability toward pH and chaotropic agents. As taken from intrinsic protein fluorescence at acid pH and varying ionic strength (pH < 4, I = 0.01 to 0.15 M), the oxidized inhibitor retains its spectral properties, whereas reduced and carboxymethylated or carboxamidomethylated ETI undergo at least partial denaturation. At alkaline pH, the oxidized protein is stable up to pH 9.5, whereas the reduced protein undergoes structural alterations at pH > 7, reaching a final plateau at pH 10.0 to 10.5. In the case of urea (U) or guanidinium chloride (GdmCl) denaturation at pH 7.0, structural transitions of the oxidized inhibitor show "hysteresis" with half-concentrations (cU)1/2 approximately 10 M and (cGdmCl)1/2 approximately 4.5 M for denaturation, and (cU)1/2 = 4.7 M and (cGdmCl)1/2 = 1.5 M for renaturation. In contrast, the reduced (and chemically modified) inhibitors exhibit true equilibrium transitions at (cU)1/2 = 0.9 M and (cGdmCl)1/2 = 0.5 M, respectively. Reduction/reoxidation in the absence and in the presence of denaturants (GdmCl) can also be applied to ETI covalently attached to a solid matrix. PMID- 8196059 TI - Crystal structures of Escherichia coli aspartate aminotransferase in two conformations. Comparison of an unliganded open and two liganded closed forms. AB - Three crystal structures of wild type E. coli aspartate aminotransferase (E.C.2.6.1.1) in space group P2(1) have been determined at resolution limits between 2.6 and 2.35 A. The unliganded enzyme and its complexes with the substrate analogues maleate and 2-methylaspartate resulted in different conformations. The unit cell parameters of the unliganded and the inhibited enzyme are a = 87.2, b = 79.9, c = 89.8 A and beta = 119.1 degrees, and a = 85.4, b = 79.8, c = 89.5 A and beta = 118.6 degrees, respectively. The crystallographic symmetry is pseudo-C222(1). The liganded enzyme structures were solved by difference Fourier techniques from that of a Val39-->Leu mutant partially refined to an R-factor of 0.22 at 2.85 A. They have a "closed" conformation like the chicken mAATase:maleate complex. The models were refined to R-factors of 0.19 (maleate complex) and 0.18 (2-methylaspartate complex) by molecular dynamics and restrained least squares methods. The unliganded crystal form was solved by molecular replacement and refined to an R-factor of 0.19 at 2.5 A resolution. The structure is in a "half-open" conformation, with the small domain rotated about 6 degrees from the closed conformation. The cofactor pyridoxal phosphate has a more relaxed conformation than in mAATase. Both maleate and 2-methylaspartate are hydrogen-bonded to the active site as in mAATase. The C alpha-CH3 bond of 2 methylaspartate is oriented at right angles to the cofactor pyridine ring, the most productive orientation for alpha-deprotonation of the substrate L-aspartate. Comparisons with earlier determined eAATase structures in space group C222(1) revealed differences that can probably be attributed to the somewhat lower resolution of the orthorhombic structures and/or mutations in the eAATases used in those studies. The present P2(1) structures confirm the justification of extrapolating properties of active site point mutants to the vertebrate isozymes. They will serve as reference in the interpretation of the properties of further site-directed mutants in continued studies of structure-function relationships of this enzyme. PMID- 8196060 TI - Amino/aromatic interactions in proteins: is the evidence stacked against hydrogen bonding? AB - We investigate the suggestion that aromatic rings can act as hydrogen-bond acceptors in proteins, by an analysis of 55 non-homologous high-resolution protein chain structures. Approximately 10% of interactions between sp2 hybridized nitrogen atoms, from either side-chains or main-chains, and phenylalanine or tyrosine rings have the nitrogen atom positioned above the ring. In these instances, however, the sp2 nitrogen atoms tend to form stacked interactions with the aromatic rings, these geometries outnumbering amino/aromatic hydrogen bonds by around 2.5:1. The statistically expected distribution, in contrast, would have only a few stacked structures and many more with larger interplanar angles, corresponding to amino/aromatic hydrogen bonds. Thus, although we do find some of these unconventional hydrogen bonds, they are clearly disfavoured relative to stacked geometries. In stacked geometries, the nitrogen-bearing groups are observed to fulfil their hydrogen-bonding potential by forming conventional, energetically stronger, hydrogen bonds with other groups in protein or solvent. This may explain the favourability of stacking. Thus, although ab initio calculations of the gas phase interaction energies for three model systems generally favour the amino/aromatic hydrogen-bonded over the stacked geometries, the differences are small enough to be outweighed easily by the additional conventional hydrogen bonding in stacked structures. PMID- 8196061 TI - Two crystal forms of the extracellular domain of type I tumor necrosis factor receptor. AB - The soluble extracellular domain of human type I tumor necrosis factor receptor (sTNFrI) is a 161 residue polypeptide found in serum and urine. This domain tightly binds tumor necrosis factors (TNF) alpha and beta and, as part of the whole receptor, initiates the powerful biological effects of TNF. The extracellular domain, typical of other TNF receptor superfamily members, comprises four cysteine-rich motifs. We have obtained two crystal forms of the sTNFrI. One crystal form is grown at pH 3.7 with MgSO4 as the precipitant. These crystals are orthorhombic, space group P2(1)2(1)2(1), with cell dimensions a = 78.5 A, b = 85.5 A and c = 67.5 A. A data set to 2.0 resolution has been collected for these crystals. Tetragonal crystals, space group P4(1)2(1)2 (or P4(3)2(1)2), with unit cell dimensions a = 69.0 A and c = 185.5 A are obtained using methylpentanediol as precipitant at pH 8.5. Data to 2.8 A have been measured from these crystals. It appears that both unit cells may contain two molecules in the asymmetric unit. These crystal structures of sTNFrI may reveal possible conformational differences between receptor localized on the cell surface (high pH), the receptor in the endosomal compartments (low pH) and the receptor in a complex with tumor necrosis factor beta. An accurate structure of the receptor and an understanding of its mechanism will provide a basis for rational drug design. PMID- 8196062 TI - Expression, purification, crystallization and preliminary X-ray analysis of human argininosuccinic acid lyase. AB - Human argininosuccinic acid lyase (ASAL) has been expressed, purified and crystallized in several distinct crystal morphologies. At present only one form is suitable for X-ray diffraction analysis. These crystals grow as hexagonal prisms, with unit cell dimensions a = b = 104.6 A, c = 185.3 A and alpha = beta = 90 degrees, gamma = 120 degrees. The crystals exhibit the symmetry of space group P3(1)21 or its enantiomorph, P3(2)21 (indistinguishable crystallographically) and diffract to a minimum d-spacing of approximately 3.5 A. PMID- 8196063 TI - Alterations in fatty acid metabolism in adriamycin cardiomyopathy. AB - Myocardial fatty acid metabolism may be impaired in adriamycin cardiomyopathy. In order to determine the extent of fatty acid metabolism alterations, we measured steady state [14C]palmitate oxidation and the incorporation of [14C]palmitate into the neutral lipid pool in a rat model of adriamycin cardiomyopathy. Isolated hearts from control rats and rats treated with adriamycin were perfused with 1.2 mmol/l of [14C]palmitate for 30 min to achieve steady state oxidation measured as [14C]O2 production; then perfused with 1.2 nmol/l of unlabelled palmitate. Hearts were killed early (0-5 min) or late (10-30 min) after the [14C]palmitate perfusion, to determine incorporation into the neutral lipid pool, and neutral lipid utilization. In the control group steady state oxidation was reached in 10 min ([14C]O2 production = 580 +/- 61 nmol/min/g dry wt) of perfusion. In the adriamycin treated group, mean CO2 production was significantly reduced at 10 min (329 +/- 44 nmol/min/g dry wt, P < 0.01 v control). At 30 min, [14C]O2 production in the treated group was not significantly different than controls (521 +/- 65 nmol/min/g dry wt v 617 +/- 36 nmol/min/g dry wt, P = N.S.). The incorporation of [14C]palmitate into the neutral lipid pool measured in the early subgroup was significantly reduced for adriamycin treated hearts v controls (7.2 +/- 0.6 v 12.0 +/- 1.4 mumol/g dry wt respectively, P < 0.01). In the control group 14C labelled neutral lipid reduced with time to 8.4 +/- 1.1 mumol/g dry wt (P < 0.05) in the late group. The adriamycin group demonstrated no significant change between early and late measurements. In conclusion, in adriamycin cardiomyopathy: (1) there is significant delay in achieving steady state palmitate oxidation, although the steady state rate is near normal; (2) palmitate incorporation into the neutral lipid pool is reduced; (3) neutral lipid pool utilization may also be reduced. These data suggest impaired uptake of palmitate into the cell in adriamycin cardiomyopathy, with a relatively maintained capacity for oxidative metabolism. PMID- 8196064 TI - The pathogenesis of free radical-induced calcium leak in cultured rat cardiomyocytes. AB - Elevated levels of intracellular calcium are generally accepted to be of critical importance in determining the outcome of cardiac myocytes exposed to ischemia and reperfusion. The mechanisms involved are obscure, but a favorite candidate is the Na-Ca exchanger operating in reversed mode, permitting calcium influx. Using exogenous free radicals and a unique, on-line, isotopic technique to measure calcium fluxes in cultured neonatal rat cardiomyocytes, we show that Na-Ca exchange is not the primary mechanism of calcium overload in this cell type during free radical exposure. We also demonstrate that neither L-type calcium channels nor general sarcolemmal defects are responsible. A specific calcium leak is present at a time when the sarcolemma remains intact with respect to its potassium permeability. The leak shares many properties with specific calcium leak channels demonstrated electrophysiologically in other tissues. It can be modulated by alterations in surface charge such that cationic amphiphiles inhibit the leak and anionic amphiphiles augment it. It is concluded that the calcium leak, in this cell type, is specific to calcium and that leak channels may be responsible. PMID- 8196065 TI - n-3 versus n-6 fatty acid incorporation into the phospholipids of rat heart sarcolemma. A comparative study of four different oil diets. AB - The fatty acid (FA) composition of the phospholipids of rat heart sarcolemma was studied after a 10-week feeding period of diets containing 10% of each of coconut oil, corn oil, linseed oil, and fish oil in comparison to a low fat diet. The major modifications observed were the following: (1) a general increase of the n 6 FA family upon corn oil administration; (2) a dual effect of linseed oil in increasing 18:2 n-6 (more than did corn oil) and decreasing 20:4 n-6 and 22:4 n 6. At the same time n-3 FA increased significantly; and (3) a significant fall in the n-6 FA following fish oil, and a marked rise in the n-3 FA. The 10-fold increase in 22:6 n-3 supports the hypothesis of an inhibition of arachidonate synthesis, as well as that of the competition for the incorporation sites of phospholipids. In general, the n-3 FA diets produced the replacement of the n-6 FA by the n-3 FA in membrane phospholipids, and led to a significant increase of the double bond index (DBI). PMID- 8196066 TI - Molecular genetics of familial hypertrophic cardiomyopathy. AB - Familial Hypertrophic Cardiomyopathy is the first inherited primary cardiomyopathy for which genetic studies have been conducted. It is an autosomal dominant inherited disease, and represents an important cause of sudden death particularly in otherwise healthy young individuals such as athletes. The first chromosomal locus has been mapped on chromosome 14 at q11-q12 where the putative gene is that encoding beta-myosin heavy chain. Several missense mutations have been identified in this gene, almost all of them are located in the region coding for the globular head of the molecule, and codon 403 is a hot-spot for mutations. Mutant alleles are expressed in both cardiac and skeletal muscles of patients where histological studies showed that gross alterations in myosin assembly do not occur. However in vitro experiments strongly suggest that mutant myosins have an impaired ability to form filaments and to interact with actin. The exact mechanisms by which myosin mutations cause FHC are not known. Very recently, three novel chromosomal loci for FHC have been identified on chromosomes 1q3, 11p13-q13, and 15q22. The challenges for the future are the identification of the other genes causing FHC, the demonstration of causal relations between the various gene defects and the development of the disease, the establishment of phenotype/genotype relationships and finally the use of genetic data for diagnostic, prognostic and maybe therapeutic purposes. PMID- 8196067 TI - Levels of the mitochondrial endonuclease during rat cardiac development implicate a role for the enzyme in repair of oxidative damage in mitochondrial DNA. AB - Mammalian heart mitochondria (MT) contain a potent Mg(2+)-dependent DNA endonuclease that becomes soluble once isolated mitochondria are disrupted using detergent. The level of this endonuclease was previously found to be markedly elevated in adult rat heart compared to other adult rat tissues. Among tissues, the level of the MT endonuclease does not appear to be correlated with the rate of MT DNA replication but rather with the rate of oxidative metabolism [Houmiel, K.L., Gerschenson, M. and Low, R.L., 1991. Biochimica Biophysica Acta 1079: 197 202]. In the present study, the level of the endonuclease has been quantitated both during rat cardiac development, from gestational day 18 through adulthood, and in cultured rat heart myoblasts. Surprisingly, the specific activity of the MT endonuclease in fetal and newborn mitochondria is high. The values are greater than 50% of that seen in the adult even though the mitochondria at this period of heart development are few and structurally disorganized. Remarkably, there is a burst of endonuclease activity at day 2 which accompanies a similar, transient elevation of respiratory complex I and IV activities. At later times, the endonuclease activity gradually increases until adulthood and correlates with steady increases in MT DNA and DNA polymerase-gamma. In cultured myoblasts, the level of the endonuclease increases about seven-fold as the growing cells reach confluency and differentiate into myotubes. These variations in the specific activity of the endonuclease, when considered along with other properties of the enzyme suggest that the endonuclease may serve a role in the removal of oxidative damage in MT DNA incurred from respiration. PMID- 8196068 TI - Analytical evaluation of high energy phosphate determination by high performance liquid chromatography in myocardial tissue. AB - High performance liquid chromatography (HPLC) is an established method for the determination of myocardial high energy phosphates (HEP). Quantification of HEP compounds in small tissue specimens obtained by endomyocardial biopsy technique requires maximal sensitivity without impairment of precision. Employing isocratic ion-pair reversed-phase HPLC, high sensitivity and precision were obtained by running analyses for adenonucleotides and creatine compounds separately at detection wavelengths of 254 and 210 nm, respectively. Further reasons for separate runs were given by the necessity for different sample preparation as remaining perchloric ion after deproteinizing and pH in the samples had various effects on adenonucleotides and creatine compounds. Mechanical homogenization for 20 s in 0.42 mol/l perchloric acid ensured a consistent myocardial HEP extraction. Sample preparation directly following biopsy sampling is preferable since HEP compounds were labile in tissue within days at -80 degrees C even though an initial metabolic inhibition in liquid nitrogen had been induced. Following extraction and neutralization, HEP compounds were stable for up to 3 months at -20 degrees C. PMID- 8196069 TI - Remodelling of microvessels by coronary hypertension or cardiac hypertrophy in rats. AB - We attempted to clarify the individual effects of coronary hypertension and ventricular pressure-overload on the remodelling of coronary arterial microvessels. We examined structural vascular changes in the right ventricular free walls using two experimental rat models: 12-week ascending aortic banding, i.e. a model of coronary hypertension without ventricular pressure-overload and 12-week pulmonary artery banding, i.e. a model of ventricular pressure-overload without coronary hypertension. In vivo peak systolic left ventricular pressure and left ventricular weight to body weight ratio in the aortic banding model increased to 198 +/- 10 mmHg and by 39% above the controls, respectively. In vivo peak right ventricular pressure and right ventricular weight to body weight ratio in the pulmonary artery banding model increased to 87 +/- 7 mmHg and by 69% above the controls, respectively. The right coronary reserve measured by the Doppler method decreased in both experimental models. Aortic banding increased the medial area and perivascular collagen to lumen area ratios in the microvessels > 30 microns in lumen diameter but not in those < 30 microns. Pulmonary artery banding increased the perivascular collagen to lumen area ratio in the microvessels < 60 microns, but not in those > 60 microns. Medial thickening was not observed over the whole range of lumen diameter. These results suggest that the mechanisms responsible for the remodelling of coronary microvessels differ between non hypertrophied hearts with coronary hypertension and hypertrophied hearts without coronary hypertension. PMID- 8196070 TI - Alterations in gene expression in the rat heart after chronic pathological and physiological loads. AB - Adaptive cardiac hypertrophy in the rat has been characterized as pathological or physiological reflecting the nature of the inciting stimulus. These two adaptations are distinguished by alterations in contractility and in the myosin ATPase composition of the affected muscle. We investigated the relative amounts of the mRNAs encoding cardiac sarcoplasmic reticular calcium ATPase (SERCA2), cardiac and skeletal troponin I (TnI), atrial natriuretic factor (ANF), and myosin light chain 1 (MLC1) in the hearts of rats that had been subjected to either conditioning by swimming (Sw), to renovascular hypertension (H) or to the combined stimulus (H-Sw) for 6 weeks. Compared to control animals, the mRNA levels for SERCA2 and cardiac TnI were slightly increased with Sw and moderately depressed with H. H-Sw animals showed a trend towards normalized mRNA levels for both genes. ANF mRNA levels were slightly elevated with Sw and markedly elevated with both H and H-Sw. MLC1 mRNA levels did not change with either or both stimuli. These data confirm that these two types of adaptive hypertrophy can be distinguished at the level of gene expression and suggest that the mechanical alterations seen in adaptive hypertrophy reflect a spectrum of pre-translational alterations which are not limited to changes in myosin heavy chain gene expression. PMID- 8196071 TI - Effect of angiotensin converting enzyme inhibition with quinaprilat on the ischaemic and reperfused myocardium. AB - We assessed whether the local inhibition of myocardial converting enzyme by quinaprilat and captopril reduces the functional and metabolic damage caused by ischaemia and reperfusion. Quinaprilat and captopril were either subcutaneously injected (0.3 mg/kg once daily for 5-6 days) in the rabbit before isolation of the heart or delivered to the isolated hearts in the perfusate (10(-6) M) 60 min before ischaemia. Cardiac protection was evaluated in terms of left ventricular pressure recovery during reperfusion, creatine phosphokinase (CPK) release, mitochondrial function, ATP and CP tissue contents, calcium homeostasis and the occurrence of oxidative stress, established by measuring content and release of reduced and oxidized glutathione. Both drugs exerted cardioprotection. Optimal myocardial preservation is achieved when quinaprilat is prophylactically administered to the rabbit. Recovery of developed pressure on reperfusion improved from 11.3 +/- 2.7 (S.E.) to 25.4 +/- 5.4 mmHg, P < 0.01 and the release of CPK was reduced from 665.8 +/- 101.4 to 231.8 +/- 81.4 mU/min/g wet wt, P < 0.01. Peak of noradrenaline release was also attenuated, from 5.253 ng/min/g wet wt to 1.764 ng/min/g wet wt. The accumulation of tissue and mitochondrial calcium was reduced from 52.3 +/- 7.5 and 44.1 +/- 5.6 to 20.5 +/- 3.2 and 27.3 +/- 4.6 nmol/kg dry wt, respectively, P < 0.01. This resulted in significant (P < 0.01) improvement of left ventricular diastolic dysfunction during ischaemia and reperfusion and in a preservation of all indices of mitochondrial function, allowing a higher recovery of ATP and CP after reperfusion (from 4.1 +/- 0.5 and 5.2 +/- 0.5 to 11.1 +/- 1.1 and 24.8 +/- 1.0 mumol/g dry wt, respectively, P < 0.01). Reperfusion-induced myocardial accumulation and release of oxidized glutathione were reduced from 0.301 +/- 0.056 and 0.318 +/- 0.083 to 0.138 +/- 0.025 nmol/mg protein and 0.076 +/- 0.012 nmol/min/g wet wt, respectively, P < 0.01. Similar results were obtained when quinaprilat was administered to the isolated heart. These data suggest that the cardioprotective effect of quinaprilat is independent from haemodynamic changes or direct reduction of toxicity due to oxygen free-radicals but it is likely to be related to a reduction in the release of noradrenaline, maintenance of high energy phosphates and membrane integrity. PMID- 8196072 TI - The effects of theophylline on aequorin light transients and force in the isolated dog right ventricular myocardium. AB - Experiments were carried out to investigate the changes in intracellular Ca2+ transients associated with biphasic contractions that were elicited during interaction of theophylline with isoproterenol in the dog ventricular myocardium. For this purpose, effects of theophylline and isoproterenol on aequorin light transients and isometric contractions were assessed in the isolated canine ventricular trabeculae, superficial cells of which had been microinjected with the Ca2+ sensitive bioluminescent protein aequorin. The positive inotropic effect of theophylline (0.1-0.3 mM) was consistently associated with an increase in the amplitude of aequorin light transients. Theophylline at concentrations of 0.6 mM and higher decreased the amplitude of aequorin light transients, but the force of contraction increased further in association with a prominent prolongation of time to peak force. Theophylline (0.3 mM) enhanced the forskolin-induced increase in aequorin light transients and force. Theophylline (2 mM) inhibited the isoproterenol-induced increase in aequorin light transients associated with early phase of contraction in a reversible manner. A late phase of aequorin light transients was induced in association with late phase of contraction in the presence of both isoproterenol and theophylline. Thus, both the early and late phase of contraction were accompanied by corresponding phases of aequorin light transients. The relation between the amplitude of force and Ca2+ transients was markedly different and the late phase of contraction was associated with much lower aequorin light transients. The late phase of aequorin light transients induced by theophylline at a high concentration (10 mM) was enhanced by isoproterenol. These results indicate that theophylline (0.1-0.3 mM) increases the amplitude of Ca2+ transients through an accumulation of cyclic AMP by inhibition of the cyclic AMP phosphodiesterase activity. In concentrations of 0.6 mM and higher theophylline decreases the amplitude of the early phase aequorin light transients probably by inhibition of release of Ca2+ from the sarcoplasmic reticulum and induces simultaneously the late phase of contraction that may be associated with an increase in responsiveness to Ca2+ of myofibrils. PMID- 8196073 TI - Decreased expression of calmodulin mRNA in human end-stage heart failure. AB - Calmodulin (CaM) is the primary Ca2+ regulatory protein in cardiac cells, thus alterations in calmodulin would greatly influence the contractile response and may play a role in the abnormal calcium handling observed in human heart failure. We used Northern blot analysis to determine changes in calmodulin mRNA expression in left ventricular tissues isolated from 20 failing and four control human hearts. Only hearts with failure due to idiopathic dilated cardiomyopathy (DCM) or ischaemic heart disease (IHD) were studied. A human calmodulin cDNA probe 95% homologous to Type 3 CaM was used, which hybridized to a single 2.3 kb mRNA. CaM mRNA levels were expressed as a function of total RNA, as determined by hybridization to an 18S cDNA probe, and as a function of myocyte specific mRNA, as determined by hybridization to a myosin heavy chain (MHC) cDNA probe. In both DCM and IHD, CaM mRNA expression relative to total RNA (CaM/18S), was significantly decreased (45% and 61%, respectively) compared to control hearts. CaM mRNA expression in DCM tissues was also significantly decreased (45%) relative to myocyte specific mRNA (CaM/MHC), when compared to control hearts. In IHD, CaM mRNA was not significantly decreased in relation to myocyte specific mRNA, which suggests a greater loss of myocytes or contractile proteins in IHD as compared with DCM. The decreased expressed of CaM mRNA observed in failing hearts could affect many Ca(2+)-dependent processes, and contribute to the inability of these hearts to handle Ca2+ in a viable manner. PMID- 8196074 TI - Are electric or magnetic fields affecting mortality from breast cancer in women? PMID- 8196075 TI - Cost-effectiveness helps sort prevention priorities. PMID- 8196076 TI - ASCO meeting highlights works in progress. PMID- 8196077 TI - NIH assessors see much to improve on campus. PMID- 8196078 TI - Concern grows over prostate cancer treatment options. PMID- 8196079 TI - The National Cancer Institute and guideline development: lessons from the breast cancer screening controversy. PMID- 8196080 TI - May we agree to disagree, or how do we develop guidelines for breast cancer screening in women? PMID- 8196082 TI - Breast cancer mortality among female electrical workers in the United States. AB - BACKGROUND: Previous epidemiologic studies have suggested that exposure to electric or magnetic fields in occupational and residential environments may cause cancer. Recent experimental findings provide some support for the hypothesis that exposure to extremely low-frequency electromagnetic fields reduces the pineal gland's nocturnal production of the hormone melatonin, thereby increasing susceptibility to sex hormone-related cancers such as breast cancer. PURPOSE: Our purpose was to assess the evidence that cancer of the female breast might be associated with exposure to extremely low-frequency electromagnetic fields. METHODS: Records of women who had breast cancer as the underlying cause of their death (ICD-9 174) and control subjects (four per case) were selected from computer files of U.S. mortality data for the years 1985-1989. Women 20 years and older at the time of their death were eligible for inclusion if they were residents of and died in one of the 24 states that provided death certification records with occupation and industry codes to the National Center for Health Statistics for at least 1 year during the study interval. Data from death certificates were used to classify the case and control subjects with regard to potential occupational exposure to electric and magnetic fields. Control subjects were a random sample of women who died of any other underlying cause, excluding leukemia and brain cancer. RESULTS: The data analysis contrasted 68 women with breast cancer and 199 controls, all with electrical occupations, with 27,814 women with breast cancer and 110,750 controls, all of whom had other occupations. Electrical workers had excess mortality from breast cancer relative to other employed women [odds ratio (OR) = 1.38; 95% confidence interval (CI) = 1.04-1.82]). Adjusted ORs for specific electrical occupations were 1.73 (95% CI = 0.92-3.25) for electrical engineers, 1.28 (95% CI = 0.79-2.07) for electrical technicians, and 2.17 (95% CI = 1.17-4.02) for telephone installers, repairers, and line workers. There was no excess of breast cancer, however, in seven other occupations held more frequently by women and also involving potentially elevated electrical exposures, including telephone operators, data keyers, and computer operators and programmers. CONCLUSIONS: In light of the limitations inherent in death certification data and the design of this study, any conclusions regarding the hypothesis that exposure to extremely low-frequency electromagnetic fields causes breast cancer among women must be limited. Nevertheless, our findings are broadly consistent with that hypothesis and encourage further investigation with improvements in study design and data quality. PMID- 8196081 TI - Phase I and pharmacologic study of the novel indoloquinone bioreductive alkylating cytotoxic drug E09. AB - BACKGROUND: A novel bioreductive alkylating indoloquinone compound, E09 [3 hydroxy-5-aziridinyl-1-methyl-2-(1H-indole-4,7-indione)- prop-F128b-en-alpha-ol], has been shown to have distinct antitumor activity against solid tumors, excellent activity under hypoxic conditions, but no notable bone marrow toxicity in preclinical models. PURPOSE: A phase I study was carried out to determine the toxicity, maximum tolerated dose (MTD), pharmacology, and antitumor response of E09. METHODS: E09 was administered as a 5-minute intravenous infusion once every 3 weeks to 32 patients with solid tumors. The starting dose of 2.7 mg/m2 was one tenth of the mouse equivalent of lethal dose to 10% of animals (MELD10). Dose was escalated by 100% until the area under the curve (AUC) at the MELD10 was reached, following a Fibonacci-like schedule. The pharmacokinetics of E09 and its metabolite E05A with an open aziridine ring was determined using a new high pressure liquid chromatographic method and noncompartmental calculation of kinetic parameters. The sigmoid Emax model was used to fit pharmacokinetic parameters to toxicity. The renal function and proteinuria were quantitated and were further evaluated by determining renal clearance ratios of immunoglobulin G (IgG) to albumin and pancreatic amylase to salivary amylase. RESULTS: The 32 patients were treated with a total of 85 assessable courses of E09. The dose limiting toxicity was proteinuria, which was accompanied by sodium and water retention. All symptoms were reversible on day 15 except in two patients, who developed acute renal failure. The ratios of IgG to albumin and pancreatic amylase to salivary amylase suggested a loss of glomerular negative charge consistent with a minimal change glomerulopathy. The pharmacokinetics of E09 showed its rapid elimination from the central compartment but with wide interpatient variation in the overall disposition of the drug. Total plasma clearance of E09 ranged from 3.2 to 24 L/min. The AUC of E09 was linearly related to the administered dose. The relationship between the AUC and proteinuria was best fitted by the sigmoid Emax model (r = .98). In two patients with adenocarcinoma of unknown primary site and in a third patient with bile duct cancer, a partial response was observed. CONCLUSIONS: The MTD of E09 was determined to be 27 mg/m2. The standard approach of drug administration is considered unsuitable because of potential renal toxicity and wide variability in the pharmacokinetics of E09. Individual dose adjustments based on plasma concentration measurements are recommended to combine maximally achievable exposure with tolerable toxicity. PMID- 8196083 TI - Efficacy of mammographic screening of the elderly: a case-referent study in the Nijmegen program in The Netherlands. AB - BACKGROUND: Only a few small studies have been conducted to examine the usefulness of mammographic screening in elderly women. These studies suggest that the screening-related reduction in breast cancer mortality rates is less than the estimated 20%-40% reduction observed for women aged 50-70 years at the time of their first screening. PURPOSE: We have studied the efficacy of continued mammographic screening for breast cancer of elderly women within our screening program. METHODS: In 1975, a breast cancer screening program was started in the city of Nijmegen. The Netherlands. During each biennial screening round, approximately 30,000 women aged 40 years and older were personally invited to participate. Single-view mammography was administered. The present study was conducted using a case-referent design. In order to be eligible for inclusion in this study, women had to have been invited to participate in the mammography screening program at least twice, with the most recent invitation having occurred when each woman was 65 years or older. The cases studied comprised 33 women in this group who had died of breast cancer at some point during 1977 through 1988. Referents were matched for age at last invitation to screening prior to the diagnosis of breast cancer and for the number of previous invitations to screenings. Five referents were randomly selected for each case. Breast cancer mortality rate ratios (RR) were calculated for several categories of attendance to the screening. RESULTS: The RR of those who attended the last screening versus those who failed to do so was 0.58 (95% confidence interval [CI] = 0.24-1.41); for women aged 65-74, the RR was 0.34 (95% CI = 0.12-0.97) and for women aged 75 or over, 2.87 (95% CI = 0.62-13.2). The RR of those who attended the screening before and after the age of 65, relative to those who attended before 65 only, was 0.26 (95% CI = 0.05-1.32). CONCLUSION: Although self-selection bias was present in our data, it was not likely to be responsible for the beneficial effect in women aged 65-74 at the time of invitation to screenings. It probably was responsible for the reversed RR (RR > 1) in the group of women 75 years and older. IMPLICATION: Continuation of mammographic screening until at least the age of 75 years may lead to a reduction of breast cancer mortality among elderly women. PMID- 8196084 TI - Nicotine: addiction and regulation. PMID- 8196085 TI - Hair coloring products: safe or still suspect? PMID- 8196086 TI - Advanced colorectal adenocarcinoma: treatment with amonafide. PMID- 8196087 TI - Pharmacokinetic behaviour of fenbendazole in buffalo and cattle. AB - Concentrations of fenbendazole and of drug metabolites in plasma were measured in buffalo and cross-bred cattle after single intraruminal administration at two different doses. Plasma concentrations of the parent compound fenbendazole and the two metabolites, viz. oxfendazole and fenbendazole sulfone, were much lower in buffalo compared with cattle, at a dose of 7.5 mg/kg body weight as indicated by lower area under concentration curve and concentration maximum. At a dose of 15 mg/kg body weight there were corresponding increases in plasma metabolite concentrations in cattle. However, buffaloes did not show a similar corresponding increase. PMID- 8196088 TI - Thiamphenicol pharmacokinetics in sheep. AB - The pharmacokinetics of thiamphenicol were investigated after intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration to sheep. It was found that the drug is almost completely absorbed following intramuscular injection, with a bioavailability of about 87.5%. Thiamphenicol appears to be widely distributed into extravascular compartments, yielding a volume of distribution [V(b)] of approximately 1 l/Kg. Elimination from the blood is relatively rapid, with a biological half-life of about 1.5 h. Oral treatment showed that thiamphenicol is absorbed from the gastrointestinal tract yielding very low plasma concentrations which were maintained for at least 24 h. Although only 30% of the oral dose was systemically available, in contrast to chloramphenicol, thiamphenicol is truly absorbed when given orally to adult sheep. One possible reason for this observation is that rumen flora do not biotransform this drug as they do for chloramphenicol. Metabolism investigations are, however, needed to confirm this finding. PMID- 8196089 TI - Comparison of oral erythromycin formulations in the horse using pharmacokinetic profiles. AB - The pharmacokinetic properties of four erythromycin formulations were compared in six adult horses after administration of single and multiple oral doses. Formulations of erythromycin administered were estolate and phosphate given 37.5 mg/kg every 12 h and 25 mg/kg every 8 h, and stearate and ethylsuccinate given 25 mg/kg every 8 h. Areas under the curve (AUC) and maximum plasma erythromycin concentrations (Cmax) were equal or greater (P > or = 0.05) following administration of erythromycin phosphate and stearate compared with those values following administration of erythromycin estolate or ethylsuccinate. In comparing an 8 h vs. a 12 h dosage interval for multiple doses of erythromycin phosphate or estolate, there were no significant differences observed in AUC(24-28 h), peak trough plasma concentrations or duration that plasma concentrations exceeded the minimal inhibitory concentration (MIC) for Rhodococcus equi. Comparisons of pharmacokinetic parameters between single and multiple doses were made for each formulation. Differences in Cmax, tmax, or t1/2 beta between single and multiple doses were demonstrated for erythromycin ethylsuccinate and estolate. Based on equivalent plasma antibiotic concentrations, erythromycin phosphate or stearate could be substituted for estolate in the treatment of Rhodococcus equi pneumonia. Furthermore, there was no advantage of an 8-h interval, compared with an interval of 12 h. PMID- 8196090 TI - Concentration of ceftiofur metabolites in the plasma and lungs of horses following intramuscular treatment. AB - Ceftiofur sodium, a broad spectrum cephalosporin antibiotic approved for veterinary use, is metabolized to desfuroylceftiofur which is conjugated to micro as well as macromolecules. Twelve horses, weighting 442-618 kg, were injected intramuscularly with a single dose of 2.2 mg ceftiofur/kg (1.0 mg/lb) body weight. Blood was collected at various intervals over 24 h after treatment. Three groups of four horses each were euthanized and lungs were collected at 1, 12, and 24 h after treatment. The concentration of desfuroylceftiofur and desfuroylceftiofur conjugates in the plasma and lungs was determined by converting them to desfuroylceftiofur acetamide (DCA) and measured DCA by high performance liquid chromatography with UV detection. The average maximum concentration (Cmax) of desfuroylceftiofur and related metabolites in plasma expressed as ceftiofur equivalents was 4.46 +/- 0.93 micrograms/ml occurred at 1.25 +/- 0.46 h after treatment. These concentrations declined to 0.99 +/- 0.16, 0.47 +/- 0.15 and 0.17 +/- 0.02 microgram/ml at 8, 12, and 24 h, respectively. The mean residence time of ceftiofur metabolites was 6.10 +/- 1.27 h. Concentrations of desfuroylceftiofur and desfuroylceftiofur conjugates in the lungs of horses expressed as ceftiofur equivalents were 1.40 +/- 0.36, 0.27 +/- 0.07, and 0.15 +/- 0.08 micrograms/ml at 1, 12, and 24 h, respectively. These concentrations of the drug at 12 and 24 h in lung homogenate were similar but slightly lower than plasma concentrations in the same horses, and the plasma pharmacokinetic values including half-life were similar to those observed at the approved dose of 1.1-2.2 mg ceftiofur/kg body weight administered intramuscularly once daily for 3-5 days in cattle. PMID- 8196091 TI - Single-dose pharmacokinetics of cefazolin in bovine synovial fluid after intravenous regional injection. AB - The pharmacokinetic properties of cefazolin in the synovial fluid of the tibiotarsal joint were determined in 10 healthy mature cattle after intravenous regional injections of 250 mg cefazolin. A pneumatic tourniquet was positioned proximal to the tibiotarsal joint and the intravenous injection was performed distal to the tourniquet. Synovial fluid concentrations of cefazolin increased in the first 30 min and fluctuated between 54.7 +/- 11.0 micrograms/ml (mean +/- SEM) and 73.2 +/- 13.2 micrograms/ml in the following 90 min while the tourniquet remained inflated. After tourniquet removal, synovial fluid concentration-time curves followed first-order one-compartment model decay in most of the animals with an elimination half-life of 0.82 h (harmonic mean). Therapeutic concentrations of cefazolin in the synovial fluid of normal joints were reached and this injection technique could be used as an alternative to systemic administration of antibiotics to provide adequate concentrations in a localized area. PMID- 8196092 TI - An image analysis system: an objective and accurate alternative for reading the agar diffusion test. AB - A computerized image analysis system (IAS) has been used to develop a new method for reading the agar diffusion test automatically. In four experiments a total of 88 porcine plasma and 95 urine samples were screened for oxytetracycline by the agar diffusion test. The inhibition zones were measured by hand and by the IAS directly from the bioassay plate and by the IAS from the photo-negative taken from the plate. Both methods were positively correlated with the hand method for plasma (0.9716, 0.9669) and urine (0.9878, 0.9731) in the range tested for 0.1 to 2.0 micrograms/ml. Moreover, the coefficient of variation and the day-to-day variation amounted to 1.72% and 1.47% respectively, for the method by hand and 1.10, 1.54% and 0.27, 0.38% respectively, for the IAS methods. It is concluded that the IAS method is an objective and accurate alternative for reading the agar diffusion test. PMID- 8196093 TI - A field evaluation of the efficacy of tolfenamic acid and oxytetracycline in the treatment of bovine respiratory disease. AB - In a blinded multicentre trial 313 cattle showing clinical signs of respiratory disease were allocated randomly into three groups, treated intramuscularly with a long-acting oxytetracycline formulation at a dose rate of 20 mg/kg bodyweight in combination with vehicle alone (placebo) or with tolfenamic acid at 2 mg/kg bodyweight once or on two occasions with a 48-h interdosing interval. The clinical status of the animals was monitored for 5 days using a specific scoring system and weight gain was calculated between day 0 and day 21. Relapses were monitored from day 5 until day 21. When oxytetracycline was combined with two injections of tolfenamic acid, there was a significant (P < 0.04) improvement in the clinical resolution. This regimen also produced non-significant improvements in cure rate, reduced frequency of relapses and improved weight gain. PMID- 8196094 TI - Pharmacokinetics of tobramycin in the camel. AB - The pharmacokinetics of tobramycin were determined in six healthy camels (Camelus dromedarius) following the intravenous (i.v.) and intramuscular (i.m.) administration of single doses of tobramycin sulphate (40 mg/ml). The half-life to tobramycin was 189 +/- 21 min and the mean residence time was 254 +/- 26 min. The apparent volume of distribution (area method) was 245 +/- 21 ml/kg, while volume of the central compartment of the two-compartment pharmacokinetic model was 110 +/- 12 ml/kg. The clearance (systemic) of tobramycin was 0.90 +/- 0.10 ml/min/kg. Values of the pharmacokinetic parameters suggest that glomerular filtration rate is lower in camels than in other ruminant species, horses, dogs and cats. Following i.m. administration of the dose (1.0 mg/kg), the drug was rapidly absorbed with peak serum concentration of 3.32 +/- 0.59 micrograms/ml at 20-30 min; the absorption half-life was 3.9 +/- 0.9 min. The systemic availability of tobramycin was 90.7 +/- 14.4%. The apparent half-life was 201 +/- 40 min, which was not significantly longer than the half-life following i.v. administration of the drug. Based on the pharmacokinetic values obtained in this study, a dosing rate of 2.5 mg/kg administered by i.m. injection at 12-h intervals can be recommended. This dosage regimen should achieve an average steady state serum concentration of 4 micrograms/ml with peak serum concentration approaching, but not exceeding, 10 micrograms/ml. PMID- 8196095 TI - Disposition and bioavailability of neomycin in Holstein calves. AB - The disposition and absorption kinetics of neomycin were studied in healthy ruminating dairy calves (n = 6), approximately 3-months-old. The calves were treated with single intravenous (i.v.) (12 mg/kg), intramuscular (i.m.) (24 mg/kg), oral (p.o.) (96 mg/kg) and repeated p.o. (96 mg/kg, b.i.d., 15 1/2 days) doses of neomycin. A 3-week rest period was allowed between treatments A and B, and B and C. Baseline and serial venous blood samples were collected from each calf. Plasma concentrations of neomycin were determined by a high performance liquid chromatography procedure. The resulting data were evaluated by using compartmental pharmacokinetic models and nonlinear least squares regression analysis. The mean of some selected parameters were t1/2 lambda 3 7.48 +/- 2.02 h, Clt = 0.25 +/- 0.04 L/h/kg, Vd(ss) = 1.17 +/- 0.23 L/kg, and MRT = 4.63 +/- 0.87 h for the i.v. data and t1/2 = 11.5 +/- 3.8 h, MRTabs = 0.960 +/- 1.001 h, F = 127 +/- 35.2%, and Clt/F = 0.199 +/- 0.047 L/h/kg for the i.m. data, respectively. Only one calf absorbed neomycin to any significant degree (F = 0.0042) after a single p.o. dose. Selected mean parameters determined after repeated oral dosing were: F = 0.45 +/- 0.45%, Cmax = 0.26 +/- 0.37 microgram/ml, and tmax = 2.6 +/- 2.9 h. Terminal half-lives determined for the i.v. and i.m. treatments were considerably longer than those reported previously in the literature. PMID- 8196096 TI - Bioavailability, pharmacokinetics and residues of chloramphenicol in the chicken. AB - The pharmacokinetic properties of chloramphenicol were determined in broiler chickens after two single oral doses (30 and 50 mg/kg body weight) and after a single intravenous (i.v.) dose (30 mg/kg body weight). After oral and i.v. administration, the plasma concentration-time graph was characteristic of a two compartment open model. After oral administration (30 and 50 mg/kg), chloramphenicol was absorbed rapidly (time to maximal concentration of 0.72 or 0.60 h) and eliminated with a mean half-life (t1/2 beta) of 6.87 or 7.41 h, respectively. The bioavailability was 29% at 30 mg/kg chloramphenicol and 38% at 50 mg/kg chloramphenicol. Concentrations greater than 5 micrograms/ml were achieved at 15 min and persisted up to 2 or 4 h post-administration, respectively. Statistically significant differences between the two routes of administration were found for the pharmacokinetic variables, half-lives of both distribution and elimination phases (t1/2 alpha, t1/2 beta) and apparent volume of distribution [Vd(area)]. The mean t1/2 beta of chloramphenicol and i.v. administration was 5.23 h. Chloramphenicol was extensively metabolized into dehydrochloramphenicol (DH-CAP), nitrophenylaminopropanedione (NPAP) and nitroso chloramphenicol (NO-CAP) derivatives. Residues of chloramphenicol (CAP) and the three metabolites DH-CAP, NPAP and NO-CAP in kidney, liver and muscle were measured in chickens that received an oral dose of 50 mg/kg once daily for 4 days. The results indicate that CAP and DH-CAP residues were cleared slowly and were at or below the detection limit of 0.005 microgram/ml within 12 days after dosing. However, at the time of slaughter (12 days), the NPAP and NO-CAP residues were detected in the tissue. PMID- 8196097 TI - Trimethoprim/sulfonamide combinations in the horse: a review. AB - The indications for use, side-effects, and pharmacokinetic parameters of trimethoprim, sulfonamides and their combinations in the horse are reviewed. Trimethoprim/sulfonamide (TMPS) combinations are used for the treatment of various diseases caused by gram-positive and gram-negative bacteria, including infections of the respiratory tract, urogenital tract, alimentary tract, skin joints and wounds. TMPS combinations can be administered orally, since absorption from the gastrointestinal tract is relatively good. However, peak serum concentrations can vary significantly between individual horses. Feed intake affects serum concentrations after oral administration. Concentrations of non bound trimethoprim (TMP) and sulfadiazine (SDZ) in synovial fluid and peritoneal fluid are equal to serum concentrations after intravenous (i.v.) administration, and high concentrations are found in urine. Concentrations of TMP and sulfamethoxazole (SMX) in cerebrospinal fluid after i.v. administration exceed the minimum inhibitory concentration for common equine pathogens. The volume of distribution is 1.5-2.7 l/kg for TMP and 0.3-0.7 l/kg for various sulfonamides. The plasma half-life of TMP is 1.9-4.3 h, whereas the plasma half-lives of the different sulfonamides vary between 2.7 and 14.0 h. About 50% of total TMP is bound to plasma proteins. The binding of sulfadoxine to plasma proteins depends on total plasma concentration and varies between 14% and 72%. The binding of other sulfonamides to plasma proteins may range from 33% for sulfaphenazole (SPZ) to 93% for sulfadimethoxine (SDM). Sulfonamides are metabolized by acetylation of the para-amino (N4) group and by hydroxylation of the methyl group and the pyrimidine ring. The metabolic pathways of TMP in the horse are not fully known. Bacterial resistance to TMPS combinations is still relatively low. The sensitivity of different micro-organisms may vary with the relative activity of the sulfonamide used in the combination. The advised oral and i.v. dose rate is 15-30 mg/kg (in a 1:5 TMP/S ratio) with a dose interval of 12 h. The acute toxicity of TMPS is low, but there have been several reports of death after i.v. administration, probably due to vagal stimulation and subsequent bradycardia and vasodilatation caused by the pharmaceutical formulation (excipients, solvents) used. Future research should concentrate on establishing the optimum pyrimidine/sulfonamide combination and its dosing regimen for antimicrobial therapy in horses. PMID- 8196098 TI - Glucuronidation of naproxen by the turtle Pseudemys scripta elegans. PMID- 8196099 TI - Protective effect of chloramphenicol against parathion-induced pulmonary oedema in rabbits: influence of sex. PMID- 8196100 TI - Glucuronidation of flumequine by the turtle Pseudemys scripta elegans. PMID- 8196101 TI - State medical boards discipline more, want role in health system reform. PMID- 8196102 TI - New data suggest needle biopsies could replace surgical biopsy for diagnosing breast cancer. PMID- 8196103 TI - From the National Institutes of Health. PMID- 8196104 TI - From the Centers for Disease Control and Prevention. Tetanus--Kansas, 1993. PMID- 8196105 TI - From the Centers for Disease Control and Prevention. Decreased susceptibility of Neisseria gonorrhoeae to fluoroquinolones--Ohio and Hawaii, 1992-1994. PMID- 8196106 TI - From the Centers for Disease Control and Prevention. Brucellosis outbreak at a pork processing plant--North Carolina, 1992. PMID- 8196107 TI - From the Centers for Disease Control and Prevention. Coccidioidomycosis following the Northridge earthquake--California, 1994. PMID- 8196108 TI - Rehabilitation for frail nursing home residents. PMID- 8196109 TI - Cost-effectiveness of screening for Chlamydia using DNA amplification. PMID- 8196110 TI - Screening for Chlamydia trachomatis: a case for empirical treatment. PMID- 8196111 TI - Urban violence in Los Angeles. PMID- 8196112 TI - Urban violence in Los Angeles. PMID- 8196113 TI - The aggravation of dementia by pilocarpine. PMID- 8196114 TI - Varicella vaccine. PMID- 8196116 TI - A piece of my mind. Baptism. PMID- 8196115 TI - Ophthalmic examination in diabetes mellitus. PMID- 8196117 TI - Longitudinal changes in adiposity associated with pregnancy. The CARDIA Study. Coronary Artery Risk Development in Young Adults Study. AB - OBJECTIVE: To examine the longitudinal associations between a pregnancy and persistent changes in adiposity in young black and white women. DESIGN: Prospective cohort study with 5 years of follow-up. SETTING: Participants recruited by community-based sampling (Birmingham, Ala; Chicago, Ill; and Minneapolis, Minn) and through the membership of a large prepaid health care plan (Oakland, Calif). PARTICIPANTS: A total of 2788 women (53% black) aged 18 through 30 years were assessed at baseline (1985 through 1986) and reassessed at examination 2 (91% retention; 1987 through 1988) and examination 3 (86% retention; 1990 through 1991). Women who remained nulliparous (n = 925) during the 5-year follow-up were compared with women who had a single pregnancy of 28 weeks' duration during that period and who were at least 12 months postpartum at follow-up (primiparas, n = 89; multiparas, n = 114). MAIN OUTCOME MEASURES: Change in body weight and in waist-to-hip ratio during the 5-year period. Analyses were adjusted for demographic factors (age and education), behavioral variables (smoking and physical activity), and baseline level of adiposity. RESULTS: Primiparas within both race groups gained 2 to 3 kg more weight during the 5-year period than did nulliparas in both adjusted and unadjusted analyses. Primiparas also had greater increases in waist-to-hip ratio that were independent of weight gain. Multiparas did not differ from nulliparas in adiposity change in either race group. At each level of parity, black women demonstrated greater adverse changes in adiposity than did white women. CONCLUSIONS: These data suggest that women experience modest but adverse increases in body weight and fat distribution after a first pregnancy and that these changes are persistent. PMID- 8196118 TI - Environmental tobacco smoke and lung cancer in nonsmoking women. A multicenter study. AB - OBJECTIVE: To determine the relative risk (RR) of lung cancer in lifetime never smokers associated with environmental tobacco smoke (ETS) exposure. DESIGN: Multicenter population-based case-control study. SETTING: Five metropolitan areas in the United States: Atlanta, Ga, Houston, Tex, Los Angeles, Calif, New Orleans, La, and the San Francisco Bay Area, Calif. PATIENTS OR OTHER PARTICIPANTS: Female lifetime never smokers: 653 cases with histologically confirmed lung cancer and 1253 controls selected by random digit dialing and random sampling from the Health Care Financing Administration files for women aged 65 years and older. MAIN OUTCOME MEASURE: The RR of lung cancer, estimated by adjusted odds ratio (OR) with 95% confidence interval (CI), associated with ETS exposure. RESULTS: Tobacco use by spouse(s) was associated with a 30% excess risk of lung cancer: all types of primary lung carcinoma (adjusted OR = 1.29; P < .05), pulmonary adenocarcinoma (adjusted OR = 1.28; P < .05), and other primary carcinomas of the lung (adjusted OR = 1.37; P = .18). An increasing RR of lung cancer was observed with increasing pack-years of spousal ETS exposure (trend P = .03), such that an 80% excess risk of lung cancer was observed for subjects with 80 or more pack years of exposure from a spouse (adjusted OR = 1.79; 95% CI = 0.99 to 3.25). The excess risk of lung cancer among women ever exposed to ETS during adult life in the household was 24%; in the workplace, 39%; and in social settings, 50%. When these sources were considered jointly, an increasing risk of lung cancer with increasing duration of exposure was observed (trend P = .001). At the highest level of exposure, there was a 75% increased risk. No significant association was found between exposure during childhood to household ETS exposure from mother, father, or other household members; however, women who were exposed during childhood had higher RRs associated with adult-life ETS exposures than women with no childhood exposure. At the highest level of adult smoke-years of exposure, the ORs for women with and without childhood exposures were 3.25 (95% CI, 2.42 to 7.46) and 1.77 (95% CI, 0.98 to 3.19), respectively. CONCLUSION: Exposure to ETS during adult life increases risk of lung cancer in lifetime nonsmokers. PMID- 8196119 TI - Effect of race on access to recombinant human erythropoietin in long-term hemodialysis patients. AB - OBJECTIVE: To quantify access to recombinant human erythropoietin (EPO) among patients with dialysis-dependent end-stage renal disease (ESRD). DESIGN: National random sample of hemodialysis patients from a random sample of dialysis units, using data abstracted from patients' medical records. SETTING: All US hemodialysis units. PARTICIPANTS: A total of 4024 Medicare-entitled in-center hemodialysis patients. MAIN OUTCOME MEASURES: The relative odds that black patients received EPO (compared with white patients). RESULTS: There was no evidence in this national study that black hemodialysis patients were more or less likely to receive EPO than white patients (P = .74). CONCLUSIONS: Three years after Food and Drug Administration approval and Medicare coverage of EPO, there was no evidence of racial disparity in access to EPO among Medicare patients with ESRD who were receiving long-term hemodialysis. However, there was evidence of greater need for EPO among black patients. PMID- 8196120 TI - Safety and immunogenicity of a recombinant outer surface protein A Lyme vaccine. AB - OBJECTIVE: To evaluate the safety and immunogenicity of a recombinant outer surface lipoprotein A (OspA) Lyme vaccine in healthy adults. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Clinical research unit of a medical center. PARTICIPANTS: Thirty-six healthy adult volunteers aged 18 through 65 years. INTERVENTIONS: Volunteers were randomly assigned to receive two 10 micrograms doses of OspA Lyme vaccine, OspA Lyme vaccine adsorbed to alum, or a buffer placebo. Subjects in the OspA Lyme vaccine group received a third dose. Patients were assessed after each vaccination for a total follow-up period of 1 year. Serum samples for antibody determination were drawn at baseline, 2 and 3 weeks after dose 1, once per week for 4 weeks after dose 2, 20 weeks after dose 2, and 1 month after dose 3. MAIN OUTCOME MEASURES: Local and systemic adverse reactions and antibody levels specific for OspA. RESULTS: The most common reactions were local pain and tenderness at the injection site. Adverse events did not increase following the second or third dose. Two doses of both vaccine formulations elicited high-titer antibodies that inhibited replication of Borrelia burgdorferi in vitro. No differences were noted in antibody levels elicited by the adsorbed and nonadsorbed formulations. CONCLUSION: Two or three doses of OspA Lyme vaccine are safe and immunogenic in adults. PMID- 8196121 TI - Kaposi's sarcoma, vascular permeability, and scientific integrity. AB - On March 13, 1992, Nakamura et al published an article in the journal Science reporting that sulfated polysaccharide peptidoglycan (SP-PG) inhibited the growth and vascular hyperpermeability characteristics of Kaposi's sarcoma-related cells and lesions in nude mice. While examining their key composite Fig 3, A through E, and related Table 2, we were surprised by several photographic features and other irregularities in the figures, which we explored further through a series of experiments. We were unable to confirm some of the pivotal findings. We communicated our concerns to Science but our letter was rejected. After submission of additional analysis, the matter was reopened by Science, but again our correspondence was rejected. Despite extensive review, the salient points raised in our initial correspondence remain unanswered or only tangentially addressed. The original conclusions by Nakamura et al are still not only highly dubious, but the validity of the peer review process and self-correcting nature of scientific inquiry are also called into question. PMID- 8196122 TI - Lung structure and function in different stages of severe adult respiratory distress syndrome. AB - OBJECTIVE: To assess the clinical consequences of duration of adult respiratory distress syndrome (ARDS) on lung structure and function. DESIGN: Retrospective analysis. SETTING: A university hospital referral center for extracorporeal support. PATIENTS: A total of 84 patients with severe ARDS (Murray score > 2.5) recruited from 48 intensive care units (1979 to 1992), who suffered ARDS and underwent mechanical ventilation for up to 1 week (37 patients with early ARDS), between 1 and 2 weeks (24 patients with intermediate ARDS), or more than 2 weeks (23 patients with late ARDS) and subsequently underwent extracorporeal support. MAIN OUTCOME MEASURES: Before beginning extracorporeal support, we measured gas exchange, pulmonary mechanics, hemodynamics, oxygen transport and delivery, incidence of barotrauma (presence of one or more thoracic tubes for pneumothorax drainage), and organ dysfunctions. In a subgroup of 16 patients, we studied lung structure by computed tomographic scan, scoring the densities and quantifying the emphysemalike lesions (bullae). RESULTS: Late ARDS showed lower respiratory compliance, higher dead space, higher PaCO2, lower venous admixture, and lower positive end-expiratory pressure requirement compared with early ARDS (P < .01). The incidence of pneumothorax (48.8% of the entire population) was significantly (P < .01) higher in late ARDS (87%) vs intermediate ARDS (46%) and early ARDS (30%). The mortality of patients with pneumothorax (66%) was significantly (P < .01) higher compared with patients without pneumothorax (46%). The number of bullae per lung was significantly higher in late ARDS vs intermediate and early ARDS (mean [SD], 8 [4], 4.3 [5], and 1.9 [3.9], respectively; P < .01), and they were preferentially distributed in the dependent lung regions. The number of bullae per lung was significantly higher in patients with pneumothorax vs those without pneumothorax (mean [SD], 13.6 [9.8] vs 1.4 [2.1]; P = .007). The mean (SD) duration of ARDS in patients with pneumothorax was 15.3 (10.0) days vs 7.0 (6.6) days in those without pneumothorax (P = .0001). No differences within the three groups were found in computed tomographic scan densities, hemodynamics, and number of organ system dysfunctions. CONCLUSIONS: The lung structure and function changes markedly with ARDS duration, and the late stages may be described as restrictive lung disease with superimposed emphysemalike lesions. Presence of pneumothorax affects survival and appears to be related to the lung structural changes occurring with time. PMID- 8196123 TI - Physicians and their patients' suicides. PMID- 8196124 TI - Parity, ponderosity, and the paradox of a weight-preoccupied society. PMID- 8196125 TI - Let's stop boxing in the Olympics and the United States Military. PMID- 8196126 TI - Clinical decision making: from theory to practice. Principles for making difficult decisions in difficult times. PMID- 8196127 TI - June 6, 1944--two doctors relive D-Day dangers. PMID- 8196128 TI - Novel treatments for liver cancer and other solid tumors show early promise. PMID- 8196129 TI - Alcohol's threat to liver transplant recipients may be overstated, suggests retrospective study. PMID- 8196130 TI - From the Centers for Disease Control and Prevention. Maternal hepatitis B screening practices--California, Connecticut, Kansas, and United States, 1992 1993. PMID- 8196131 TI - From the Centers for Disease Control and Prevention. Frequent alcohol consumption among women of childbearing age--behavioral risk factor surveillance system, 1991. PMID- 8196132 TI - From the Centers for Disease Control and Prevention. Increasing incidence of low birthweight--United States, 1981-1991. PMID- 8196133 TI - From the Centers for Disease Control and Prevention. International decade for natural disaster reduction. PMID- 8196134 TI - Syringe and needle exchange to prevent HIV infection. PMID- 8196135 TI - Mammographic screening. PMID- 8196136 TI - Mammographic screening. PMID- 8196137 TI - The risk of in utero exposure to lithium. PMID- 8196138 TI - Factors influencing primary cesarean rates. PMID- 8196139 TI - Emergence of drug-resistant pneumococcal infections in the United States. AB - OBJECTIVE: To estimate drug susceptibility patterns of Streptococcus pneumoniae in selected hospitals in the United States and to characterize the epidemiology of invasive drug-resistant pneumococcal infections. DESIGN: Minimum inhibitory concentrations (MICs) for a variety of commonly used antimicrobial drugs were determined for pneumococcal isolates submitted to the Centers for Disease Control and Prevention (CDC). Risk factors for drug-resistant pneumococcal infection were evaluated. SETTING: Hospital laboratories in the United States submitting pneumococcal isolates to the CDC between October 1, 1991, and September 30, 1992. PARTICIPANTS: A total of 544 persons with pneumococci isolated from normally sterile sites. RESULTS: A total of 13 hospitals in 12 states actively participated in an ongoing pneumococcal surveillance study. Resistance to penicillin was detected in 6.6% of isolates, including 1.3% of isolates with MICs of 2.0 micrograms/mL or more (compared with < 0.02% of isolates with MIC > or = 2.0 micrograms/mL identified by CDC surveillance from 1979 to 1987). A total of 16.4% were resistant to at least one of the following drugs or drug classes: penicillin, cephalosporins, macrolides, combination trimethoprim and sulfamethoxazole, and chloramphenicol. Six serotypes (6B, 23F, 14, 9V, 19A, and 19F) accounted for nearly 85% of strains resistant to at least one drug class. Children were more likely than adults to be infected with strains resistant to trimethoprim-sulfamethoxazole, erythromycin, or chloramphenicol. CONCLUSIONS: Emergence of drug-resistant pneumococcal infections will present critical challenges to clinicians for treating patients with pneumococcal disease. Widened and intensified surveillance is needed. These data suggest that current recommendations for use of 23-valent pneumococcal capsular polysaccharide vaccines should be aggressively promoted and that development and evaluation of new conjugate pneumococcal vaccines may be a crucial part of strategies for prevention. PMID- 8196140 TI - Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. AB - OBJECTIVE: To further define the safety and efficacy of recombinant human interleukin 1 receptor antagonist (rhIL-1ra) in the treatment of sepsis syndrome. STUDY DESIGN: Randomized, double-blind, placebo-controlled, multicenter, multinational clinical trial. POPULATION: A total of 893 patients with sepsis syndrome received an intravenous loading dose of rhIL-1ra, 100 mg, or placebo followed by a continuous 72-hour intravenous infusion of rhIL-1ra (1.0 or 2.0 mg/kg per hour) or placebo. OUTCOME MEASURE: Twenty-eight-day all-cause mortality. RESULTS: There was not a significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication (n = 893; generalized Wilcoxon statistic, P = .22) or among patients with shock at study entry (n = 713; generalized Wilcoxon statistic, P = .23), the two primary efficacy analyses specified a priori for this trial. Results from secondary analyses suggest an increase in survival time with rhIL 1ra treatment among patients with dysfunction of one or more organs (n = 563; linear dose-response, P = .009). Retrospective analysis demonstrated an increase in survival time with rhIL-1ra treatment among patients with a predicted risk of mortality of 24% or greater (n = 580; linear dose-response, P = .005) as well as among patients with both dysfunction of one or more organs and a predicted risk of mortality of 24% or greater (n = 411; linear dose-response, P = .002). CONCLUSIONS: There was not a statistically significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication or among patients with shock at study entry. Secondary and retrospective analyses of efficacy suggest that treatment with rhIL-1ra results in a dose-related increase in survival time among patients with sepsis who have organ dysfunction and/or a predicted risk of mortality of 24% or greater. PMID- 8196141 TI - The effect of transplant center volume on cardiac transplant outcome. A report of the United Network for Organ Sharing Scientific Registry. AB - OBJECTIVE: The number of cardiac transplant programs continues to increase despite no increase in the number of hearts available for transplantation. As a result, the majority of heart transplant centers perform extremely small numbers of transplant operations annually. To determine the effect of small transplantation volume on transplant outcome, the following study was performed. DESIGN: Using the Scientific Registry of the United Network for Organ Sharing, all cardiac transplant procedures from October 1987 through December 1991 were analyzed to determine whether center volumes affected cardiac transplant outcome. Patient survival rates for each center were determined, and the survival rates were modeled for the following patient variables: first transplantation or retransplantation, patient condition at the time of transplantation, patient underlying cardiac disease (congenital vs all others), and time. SETTING: All cardiac transplant centers in the United States were included in the analysis. PATIENTS: All patients undergoing cardiac transplantation in the United States from October 1987 through December 1991 were included in the analysis. MAIN OUTCOME MEASURE: The primary end point in this analysis was mortality. RESULTS: Throughout the entire study, of the 150 cardiac transplant centers, 35.3% of the centers were performing fewer than five cardiac transplantations per year, 53.3% were performing fewer than nine transplantations per year, and 61.3% were performing fewer than 12 transplantations per year, the minimum required for Medicare payment eligibility. Using the modeled survival rates, the risk of mortality decreased to a basal level in those centers performing between eight and 10 transplant operations per year. In centers performing fewer than nine transplantations, mortality increased sharply and exponentially. Dividing centers into those that performed nine or more transplantations per year (70 centers) and fewer than nine transplantations per year (80 centers), the increased risk of mortality at 1 month and 12 months was 40.3% and 33.1%, respectively, in centers performing fewer than nine cardiac transplantations per year (P < .001). Once the threshold of nine transplant procedures was met, those centers that were eligible for Medicare payment did not have significantly better survival than those centers not eligible for Medicare coverage. CONCLUSIONS: These data demonstrate that the risk of mortality at early and intermediate time points is substantially higher in low-volume cardiac transplant centers, which make up more than half of the centers performing cardiac transplantation in the United States. PMID- 8196142 TI - Children in foster care in the state of Washington. Health care utilization and expenditures. AB - OBJECTIVE: To determine and compare health care utilization and expenditures of children in foster care with those of other children and to identify and describe high-cost children in foster care. DESIGN: Analysis of the Medicaid program claims data in the state of Washington. POPULATION: A total of 1631 children in foster care and 5316 children in the Aid to Families With Dependent Children (AFDC) program in 1990. The children were ages 0 through 7 years and eligible for Medicaid continuously during the study year. MAIN OUTCOME MEASURES: Health care utilization and expenditures classified by types of health service and health care provider; proportion of children with 1990 expenditures exceeding $10,000 and most prominent diagnoses associated with their health care utilization. RESULTS: Mental health services were used by 25% of children in foster care compared with 3% of AFDC children (P < .001), and supportive services of visiting nurses and physical therapists were used by 13% of children in foster care and 1% of AFDC children (P < .001). Twice as many children in foster care than AFDC children used medical equipment or specialist services or were hospitalized (P < .001). Mean health care expenditures in 1990 were $3075 for children in foster care and $543 for AFDC children (P < .001). High-cost children included 8% of children in foster care and 0.4% of AFDC children. Among the high-cost children in foster care (n = 106), 59% had mental disorders and 31% had congenital conditions. CONCLUSIONS: Results suggest a higher prevalence and greater complexity of illnesses, particularly mental disorders, among children in foster care. Despite the high utilization and cost of mental health services, previous research suggests there may be underutilization of these services compared with need. Appropriate allocation of resources is essential if foster care agencies are to adequately meet the diverse and compelling needs of children in foster care. PMID- 8196143 TI - Comparison of in-line skating injuries with rollerskating and skateboarding injuries. AB - OBJECTIVE: To describe the estimated relative frequency, types of injuries, and demographic features of people injured while in-line skating, rollerskating, and skateboarding in the United States. DESIGN: Case series. SETTING: Emergency department visits to hospitals participating in the National Electronic Injury Surveillance System. PARTICIPANTS: All persons treated for a product-related injury involving in-line skates, rollerskates, or a skateboard between July 1, 1992, and June 30, 1993. RESULTS: Approximately 30,863 persons (95% confidence interval, 23,073 to 38,653) were treated for in-line skating injuries during the study period. For every in-line skating injury, approximately 3.3 rollerskating and 1.2 skateboarding injuries occurred (P < .0001). The median age of those injured in these three sports was 15, 12, and 13 years, respectively (P < .0001). Sixty-three percent of injured in-line skaters had a musculoskeletal injury, including 37% with a wrist injury, of which two thirds were fractures and/or dislocations. Five percent of all injured in-line skaters had head injury and 3.5% of the injured in-line skaters required hospitalization. CONCLUSIONS: In line skating and skateboarding injuries resulted in a similar number of emergency department visits, but fewer than that for rollerskating injuries. Because wrist fractures were the most common type of injury in all three sports, wrist protection is needed. Head protection by helmets is recommended. PMID- 8196144 TI - The rational clinical examination. Physical examination of the liver. PMID- 8196145 TI - Interim guidelines for management of abnormal cervical cytology. The 1992 National Cancer Institute Workshop. PMID- 8196146 TI - Health system reform in the Czech Republic. Policy lessons from the initial experience of the general health insurance company. AB - The Czech Republic is among the most aggressive of the former Warsaw Pact countries in encouraging competition and free-market reform. This aggressiveness was extended into the health care sector when, in 1992, a mandatory employment based health insurance system was introduced. The move from a controlled socialist structure to an insurance-based, fee-for-service model occurred in a short time. Health care spending increased 50% in 2 years and now approaches that of many industrialized nations. Claims for reimbursements are increasing at a rate of 5% to 7% per quarter. Market incentives have changed behaviors within the medical community. Newly privatized physicians generate greater volume and consume more resources than those continuing as state employees. Policy issues requiring further evaluation include supply, distribution, and relative valuation of physician services; clinical resource allocation; and cost containment. PMID- 8196147 TI - Drug-resistant pneumococcal infections in the United States. A problem for clinicians, laboratories, and public health. PMID- 8196148 TI - Sepsis therapy trials. Continued disappointment or reason for hope? PMID- 8196149 TI - Sickle cell disease in nonblack persons. PMID- 8196150 TI - Metallic surgical clips and magnetic resonance imaging. PMID- 8196151 TI - The effect of pravastatin on prevention of restenosis after successful percutaneous transluminal coronary angioplasty. AB - Numerous attempts have been made to prevent late restenosis after successful percutaneous transluminal coronary angioplasty (PTCA), but there is still no effective treatment. This report describes the effect of an oral lipid-lowering agent, pravastatin, on restenosis after successful PTCA. Sixty-six patients who underwent successful elective PTCA were assigned to a pravastatin-treated group (Group 1, n = 29) or an untreated group (Group 2, n = 37) in a prospective and randomized fashion. Pravastatin (5 mg or 10 mg twice a day) was given to Group 1 patients from day 3 after the procedure. Selective coronary angiography was repeated 3 to 5 months later, or sooner if the patient developed angina pectoris. The serum cholesterol level was decreased significantly in Group 1 (from 215.7 +/ 44.3 mg/dl to 181.2 +/- 30.3 mg/dl, p < 0.001), but not in Group 2 (from 191.9 +/- 30.8 mg/dl to 191.8 +/- 33.3 mg/dl, p = ns), at the time of repeat coronary angiography. However, there were no differences between the groups with regard to the recurrence of angina, the need for repeat PTCA, or restenosis, as assessed by quantitative analysis of coronary cineangiograms. These results suggest that oral pravastatin therapy does not effectively prevent late restenosis after successful PTCA by this mode of administration. PMID- 8196152 TI - Simultaneous dual myocardial imaging with iodine-123-beta-methyl iodophenyl pentadecanoic acid (BMIPP) and thallium-201 in patients with coronary heart disease. AB - To assess the clinical value of simultaneous dual myocardial imaging with iodine 123-beta-methyl-iodophenyl-pentadecanoic acid (123I-BMIPP) and thallium-201 (201Tl), myocardial imaging was performed at rest and during exercise in seven patients with coronary heart disease. When 123I-BMIPP and 201Tl images were compared, the initial exercise and resting images agreed 87% and 64%, respectively. In the initial resting images, the regional uptake of 123I-BMIPP was frequently less than that of 201Tl. The incidence of exercise-induced reversible defects by 201Tl in the Tl > BMIPP regions was significantly higher than that in the Tl = BMIPP regions (57% vs 4%, p < 0.01) and the incidence of coronary narrowing of more than 90% in the Tl > BMIPP regions was also significantly higher than that in the Tl = BMIPP regions (91% vs 38%, p < 0.01). In addition, this disparity (Tl > BMIPP) was found more frequently in regions with abnormal wall motion than in regions with normal wall motion (hypokinetic regions; 68%, severe hypokinetic or akinetic regions; 50%, vs normokinetic region; 4%, p < 0.01). In contrast, the uptake of 123I-BMIPP correlated closely with that of 201T1 in normal myocardium and the uptake of both 123I-BMIPP and 201Tl was severely reduced in myocardium with severe ischemia during exercise and prior infarction. These results indicate that dual myocardial imaging with 123I BMIPP and 201Tl may provide a unique means of identifying patients with metabolically disturbed myocardium, such as hibernating and stunned myocardium. PMID- 8196153 TI - Left ventricular function of the heart regressed by nifedipine in spontaneously hypertensive rats. AB - Left ventricular (LV) performance of the pharmacologically regressed heart in hypertension is still unclear. We compared LV function of the heart regressed by nifedipine with that of the hypertrophied heart in spontaneously hypertensive rats (SHR). Nifedipine (30 mg/kg/day in food) was given to 15-week-old male SHR for 20 weeks (n = 12). Age- and sex-matched SHR served as controls (n = 12). LV catheterization was performed using a micromanometer and cardiac output was determined by the thermodilution method. Hemodynamic studies were performed after washout of nifedipine (24 h), when blood pressure had returned to the untreated level. Peak pumping ability was assessed during acute volume loading with saline. Nifedipine significantly decreased blood pressure in conscious animals (222 +/- 11 to 201 +/- 12 mmHg, p < 0.01) and reduced LV weight (1.20 +/- 0.07 to 1.07 +/- 0.05g, p < 0.01). After washout of nifedipine, LV systolic and end-diastolic pressures, dp/dtmax and cardiac output determined under pentobarbital anesthesia were similar in the treated and untreated groups. Peak pumping ability during acute preload elevation was also similar in the 2 groups. Plasma norepinephrine was unaltered, and plasma renin activity was significantly lower in the treated rats (p < 0.05). These results indicate that nifedipine regressed LVH with a minimal reduction of blood pressure and without evidence of neurohumoral activation or volume retention. In conclusion, LV function of the heart regressed by nifedipine was preserved after a spontaneous rise in blood pressure and during acute preload elevation. PMID- 8196154 TI - Histopathology of canine hearts subjected to catheter ablation using radiofrequency energy. AB - To investigate the pathologic changes of the myocardium and the adverse effects of radiofrequency (RF) catheter ablation, we observed canine hearts that had been ablated by RF energy. Catheter ablation was administered to three sites of the hearts of 46 dogs: endomyocardium, coronary sinus, and atrioventricular junction. The dogs were sacrificed 0-12 weeks after ablation and the lesions were stained with hematoxylin-eosin and Azan stain. Each ablated lesion was well demarcated from the adjacent normal tissue. The margin between the ablated lesion and normal tissue became clearer with time. The lesions were hemispherical and measured about 2 to 10 mm in diameter and 1 to 6 mm in depth. Histologic examination in the acute phase demonstrated the presence of coagulation necrosis of the myocardium, interstitial hemorrhage and edema, followed by infiltration of inflammatory cells. Granulation tissue replaced the normal myocardium. In the chronic phase, the lesions became fibrotic and fatty. A mural thrombus was found in 30% of the cases of endomyocardial ablation and 50% of the right ventricular lesions were transmural. Ablated lesions in the coronary sinus extended to the left atrium and left ventricle. Obstruction of the coronary sinus was observed in 8% of the ablated dogs. Most of the lesions with complete atrioventricular block were ablated at the His penetrating region of the conduction system. Thus, since the ablated lesions were clearly delineated, catheter ablation using RF energy appears to eliminate only the target area. PMID- 8196155 TI - Effects of alpha-human natriuretic peptide on renal hemodynamics and diuresis in dogs and perfused rat kidneys. AB - Effects of alpha-human atrial natriuretic polypeptide (alpha-hANP) on renal function were studied in anesthetized dogs and isolated perfused rat kidneys. Two doses of alpha-hANP were used to determine whether renal hemodynamics or tubular reabsorption is tha major factor in the diuretic action of alpha hANP. The excretion rates of sodium (Na) and inorganic phosphate (PO4) were evaluated to determine the site of diuretic action in the renal tubule. In dogs that received the smaller dose of alpha-hANP (5 ng.kg-1.min-1) infused into the renal arteries without changes in systemic or renal hemodynamics, urine volume (UV) and urinary Na excretion (UNaV) increased significantly. Fractional excretion of Na (FENa) was increased, while fractional excretion of PO4 (FEpo4) was unchanged, following the infusion of alpha-hANP. The calculated fractional Na reabsorption in the distal tubule (DTRNa) during the infusion of alpha-hANP was significantly suppressed. In dogs that received the a larger dose of alpha-hANP (50 ng.kg-1.min 1), the glomerular filtration rate (GFR), UV, and FENa were increased and DTRNa was decreased. In isolated rat kidneys perfused at a constant pressure, a lower concentration of alpha-hANP (0.5 ng.ml-1) in the perfusate caused diuresis and increased Na and PO4 excretion without any renal hemodynamic alterations. A higher concentration of alpha-hANP (5 ng.ml-1) increased GFR, Na and PO4 excretion. Since PO4 reabsorption is believed to occur primarily in the renal proximal tubule, these findings suggest that the diuretic action of alpha-hANP in smaller doses in induced by direct action on renal distal nephron.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196156 TI - Systolic anterior motion of the mitral valve associated with acute myocardial infarction in a 62-year-old patient. AB - A 62-year-old patient was admitted to our hospital for treatment of early gastric cancer. After total gastrectomy, he suffered from anteroseptal myocardial infarction. Systolic anterior motion of the mitral valve which was not observed before surgery was observed during the acute phase of myocardial infarction and completely disappeared 3 weeks after the onset of myocardial infarction. Systolic anterior motion of the mitral valve in this patient may have been caused by changes in left ventricular wall motion during the acute phase of myocardial infarction. PMID- 8196157 TI - Large left-to-right shunt through a small atrial septal defect produced by progressive aortic stenosis in the elderly--a case report. AB - We present a 74-year-old female who showed a large left-to-right shunt through a small atrial septal defect presumably due to diastolic dysfunction of the left ventricle caused by the progression of aortic stenosis. Accordingly, elderly patients with even small atrial septal defect should be followed carefully, since diastolic dysfunction of the acquired left ventricular disorder could increase the left-to-right shunt. PMID- 8196158 TI - Haemo-dialysis/-filtration using sodium bicarbonate depresses cardiac function in critically ill patients with acute renal failure. AB - The effect of sodium bicarbonate haemodialysis or haemofiltration on cardiac function was prospectively studied in 8 patients with acute renal failure. All of the patients exhibited consciousness disturbance and seven patients were on mechanical ventilation. All but one of the patients demonstrated moderate hyperlactataemia and seven patients were receiving vasoactive amine support. Arterial and mixed venous gas analysis and haemodynamic measurements were performed before and after haemodialysis/-filtration treatment. The buffer was changed in a randomised order between bicarbonate and acetate and 11 crossover studies were completed. After treatment with bicarbonate, the cardiac index and stroke index decreased significantly (4.0 +/- 0.3 to 3.4 +/- 0.4 L/ min/m2, p < 0.05 and 39.6 +/- 2.5 to 32.9 +/- 1.8 L/m2, p < 0.05), whereas no significant changes were observed in cardiac index or stroke index after treatment with acetate. Therefore, the post-dialytic percent changes of cardiac index, stroke index and left ventricular stroke work index were significantly decreased after bicarbonate sessions, as compared to after acetate sessions. Haemo-dialysis/ filtration using sodium bicarbonate can depress cardiac function in critically ill patients on mechanical ventilation with disturbed consciousness, and in those who are receiving vasoactive amine support due to uncompromised haemodynamics associated with hyperlactataemia. PMID- 8196159 TI - Improvement of regional wall motion in medically treated myocardial infarction with single-vessel coronary artery disease. AB - Long-term changes in regional wall motion (RWM) following acute myocardial infarction (AMI) in 42 patients with uncomplicated single-vessel disease were examined retrospectively by repeat cardiac catheterizations. The first and second cardiac catheterizations were performed at an average of 28 days and 6.6 years after the onset of AMI, respectively. All 42 patients underwent first and second cardiac catheterizations without undergoing coronary artery bypass surgery or coronary angioplasty. Regional left ventricular functions were analyzed by the centerline method using a right anterior oblique left ventriculogram. The wall motion abnormality score (WMAS) was defined as [# chord below -2SD] x [mean SD chord below -2SD]. The improvement in the WMAS was more prominent in cases with an occluded infarct-related artery. Thus, we concluded that 1) RWM improves significantly with medical treatment in long-term follow-up in cases of uncomplicated AMI with single-vessel disease, and 2) the improvement of RWM is completed within the first few weeks after AMI in cases with a patent infarct related artery. PMID- 8196160 TI - The role of the accessory pathway in the onset of atrial fibrillation in Wolff Parkinson-White syndrome--electrophysiological examination before and after surgical ablation. AB - To determine the role of the accessory pathway in the pathogenesis of atrial fibrillation, we compared electrophysiological findings in 17 patients (44.7 +/- 10.2 years) with a history of atrial fibrillation before and after surgical ablation of the accessory pathway. The PA interval was shortened, and the atrial refractory periods and the potential minimal wavelength of an atrial impulse (FRPA/PA) were significantly increased, after surgery. Fragmented atrial activity (an increase of 150% or more in the duration of the high right atrial electrogram) was observed in 80% of the patients before surgery and in 25% after surgery. Its zone was significantly decreased after surgery. Repetitive atrial firing was defined as the occurrence of 3 or more successive atrial electrograms induced by a premature stimulation. This was observed in 60% of the patients before surgery, but in none after surgery. Atrial fibrillation was induced in 16 patients during the preoperative study, but in only 1 patient postoperatively. In conclusion, these results suggest that accessory pathways affect atrial vulnerability and play an important role in the onset of atrial fibrillation in WPW syndrome. PMID- 8196161 TI - [Cloning and characterization of the human thyrotropin-releasing hormone receptor: regulation of thyrotropin-releasing hormone receptor mRNA levels by thyroid hormone]. AB - 1) We successfully cloned a human thyrotropin-releasing hormone receptor (TRH-R) gene. The human TRH-R consists of 398 amino acids and is a member of the G protein-coupled receptor family. The gene has a single intron in the coding sequence. Although highly homologous to the rat and mouse TRH-Rs, the human TRH-R has several differences in the carboxyl-terminal structure. 2) We next studied the effect of thyroid status on TRH-R mRNA levels both in vivo and in vitro. TRH R mRNA levels in hypothyroid rats were increased significantly, while no significant changes were observed in vitro. The data indicate that thyroid hormone may regulate TRH-R mRNA levels in different manners in vitro and in vivo. PMID- 8196162 TI - [TRH receptor-related signal transduction mechanism]. AB - TRH receptor-related signal transduction mechanism in the pituitary cells and the central nervous system was reviewed. In pituitary cells, TRH binds to its specific receptor on the cell membrane, followed by hydrolysis of inositol phospholipids by activation of phospholipase C leading to an increase in inositol 1,4,5-trisphosphates (IP3) and diacylglycerol (DG). IP3 mobilizes intracellular Ca2+, which activates Ca2+ and Calmodulin dependent protein kinase (Ca-CaM kinase) and DG activates protein kinase C (PKC). Both Ca-CaM kinase and PKC phosphorylates several proteins in the nucleus, plasma membranes, and cytosol resulting in cell responses including hormone secretion and gene expression. Protein dephosphorylation is also involved in TRH action in the pituitary. In the central nervous system, TRH possesses different intracellular signaling systems, which vary with brain regions. PMID- 8196163 TI - [DNA typing of HLA antigen in patients with autoimmune thyroid disease using the PCR-SSOP method]. AB - The purpose of this study was to investigate HLA-linked genetic factors involved in the pathogenesis of autoimmune thyroid disease such as Graves' disease and Hashimoto's thyroiditis. In 76 Graves' disease patients and 317 healthy Japanese controls, HLA-A, -B, -C, DR and DQ specificities were determined by serologic typing and HLA-DPB1 alleles were typed by DNA typing using the PCR-SSOP method. The frequencies of HLA-A2, B46 and DPB1*0501 were increased in Graves' patients. The highest odds ratio (10.5) was observed in individuals possessing both DPB1*0501 and HLA-A2. This observation suggests a synergic involvement of HLA class II allele (DPB1*0501) and an HLA class I allele (HLA-A2) in the pathogenesis of Graves' disease. Genotypes of DQA1 and DQB1 genes were determined by the PCR-SSOP method in 105 patients with goitrous Hashimoto's thyroiditis to investigate whether specific DQ alleles were associated with susceptibility or resistance to autoimmune thyroid disease. Hashimoto's thyroiditis was found to be negatively associated with DQA1*0102 and DQB1*0602. No strong positive association with a specific DQ allele was found in Hashimoto's thyroiditis. These results suggest that the HLA-DQ gene may be a genetic marker for resistance to Hashimoto's thyroiditis. PMID- 8196164 TI - [Comparison of immunogenic regions in TSH receptor for Graves' IgG and Hashimoto's IgG]. AB - Immunogenic regions in human TSH receptor responsible for autoimmune thyroid disease have been studied using synthetic TSH receptor-related peptides. Eight different peptides corresponding to segments of the extracellular domain of TSH receptor were synthesized. Immunoglobulin G (IgG) of patients with Graves' disease significantly bound to peptide #1 (32-56) compared with IgG of control subjects, and IgG of three of eight patients with Graves' disease showed increased binding to peptide #5 (309-337). In contrast, IgG of patients with Hashimoto's thyroiditis significantly bound to peptide #8 (333-359). The binding rates of Hashimoto's IgG to peptide #8 positively correlated with both MCHA and TGHA titers. These results suggest that heterogeneity of binding sites in TSH receptor for autoimmune thyroid disease may be responsible for pathophysiology of hyperthyroidism and hypothyroidism. PMID- 8196165 TI - [Unique association of p53 mutations with undifferentiated carcinoma of the thyroid]. AB - In thyroid there is a wide variety of tumors varying from slowly growing differentiated adenocarcinomas to rapidly proliferating undifferentiated carcinomas. There has been some histopathological evidence that the undifferentiated thyroid carcinomas are derived from differentiated carcinomas. Moreover, it is suspected that some genetic events might be associated with such changes. To identify these genetic events that must be involved in thyroid tumor progression, we initially investigated p53 gene alterations in 10 papillary adenocarcinomas, 4 follicular adenocarcinomas, and 8 undifferentiated carcinomas. Base substitutional mutations in exons 5 to 8 and loss of heterozygosity (LOH) of the p53 gene were not detected in papillary or follicular adenocarcinomas. However, 7 of 8 undifferentiated carcinomasa were carrying base substitutional mutations, and LOH was detected in 3 of 5 informative cases. These results strongly suggest that the mutated p53 gene plays a crucial role in de differentiation during the progression of thyroid tumors. PMID- 8196166 TI - [Specific amplification by PCR for N-ras mutation in thyroid follicular cartinoma]. AB - Mutation-specific PCR amplification, a special version of allele-specific amplification, is a method for detection of known mutation. In this method, one of the paired primers has a base at the 3' terminal that is complementary to a mutated base. With this primer, only alleles which have the same mutation can be amplified. We analyzed point mutations of N-ras protooncogene codon 61 in thyroid neoplasms using this mutation-specific PCR amplification method. This method is easy to perform, and many samples can be treated at one time. We detected 2 point mutations of N-ras codon 61 out of 7 follicular carcinomas. One was a cytosine to adenine substitution mutation at the first base, and the other was an adenine to guanine substitution mutation in the second base. These mutations were not detected in 7 follicular adenoma and 1 papillary carcinoma. The results were confirmed by both dot blot hybridization and direct sequencing. Mutation-specific amplification is a powerful method for detection of known mutations of protooncogenes or tumor suppressor genes in investigation of the cancer biology. PMID- 8196167 TI - [Body mapping of human genes]. AB - The ultimate goal of the human genome project to decode all the genetic information carried in the genome. Towards this goal, the physical structure of the genome, as well as the functional aspects of the genome, must be understood. We initiated a cDNA project to collect the "expression profiles" of all human genes, a database with which to describe which genes are expressed, and to what extent, in any given human cell at a particular time. Single-cycle sequencing of randomly selected members from a 3'-directed cDNA library is most appropriate for this purpose: the sequence data serve as a "gene signature" to identify the expressing gene, and the frequency of appearance of the gene signature reflects the activity of the gene. The compiled data, which usually covers some 1000 sequencing results per sample, is referred to as an "expression profile". We applied this analysis to HepG2 (a cell line derived from a hepatocellular carcinoma), liver cells and lung cells. The expression profiles shed some light upon the unique features of gene expression in the cell or tissue tested. A comparison of the expression profiles among different cells has allowed active genes to be classified as housekeepers or those with cell-specific functions. A significant fraction of the abundantly expressed genes include those that are unique to the cell. In addition, the resulting collection of thousands of gene signatures is a useful source of probes for mapping and for isolating full size cDNAs. PMID- 8196168 TI - [Pathogenesis of Graves' disease]. AB - The discovery of long acting thyroid stimulator in Graves' disease and autoantibodies specific for the thyroid in Hashimoto disease in 1956, were the earliest examples of autoimmune responses. Autoimmune thyroid disease has many important advantages in the investigation of autoimmune disease when compared to the other disease. It is possible to obtain thyroid tissue at biopsy and to investigate the histology by various methods and the interactions between thyrocytes and infiltrated mononuclear cells in vitro. Important autoantigens, such as the TSH receptor, thyroid peroxidase and thyroglobulin have already been cloned and each autoantigen has a specific function. Furthermore, we can observe precisely the clinical course of the disease using laboratory parameters. In this review, the pathogenesis of Graves' disease will be overviewed using the results obtained, mainly in our laboratory, in the following topics: (1) Immunogenetics: HLA class I and II, Gm, multiple genes (2) Trigger: bacteria, retrovirus (HIV, HTLV-I), radiation (3) Initiation and perpetuation of autoimmune responses: role of HLA class I and II antigens, characteristics of infiltrated mononuclear cells, interactions among thyrocytes, mononuclear cells and endothelial cells, role of cytokines, adhesion molecules (4) Autoantibodies: methods of determination and clinical correlates of TSH receptor antibodies (5) Autoantigens: structure and functional relationship of TSH receptor (6) Future studies: possible methods of treatment based on pathogenesis, a model of new treatment. PMID- 8196169 TI - [Current topics on molecular thyroidology: clinical significances]. PMID- 8196170 TI - [Molecular mechanism of thyroid hormone synthesis]. AB - Thyroid peroxidase catalyzes the two-electron oxidations of tyrosine and monoiodotyrosine, and one-electron oxidation of diiodotyrosine. This difference in the oxidation, with tyrosine and diiodotyrosine, is also observed in the reaction of thyroid peroxidase with 0.2 and 0.7% iodine thyroglobulins. The results support the hypothesis that the increase in the diiodotyrosine residue in thyroglobulin inhibits further iodination by switching the catalytic cycle to oxidative coupling, to form thyroid hormones. Thyroid hormone synthesis requires iodide, H2O2, thyroglobulin and thyroid peroxidase. The stimulation of iodide uptake and H2O2 generation in the thyroid, as well as, protein synthesis of thyroglobulin and thyroid peroxidase in response to TSH has been reported. The regulation of thyroid hormone synthesis in the thyroid peroxidase reaction and through the peroxidase system is summarized. PMID- 8196171 TI - [Thyroid peroxidase (TPO) gene and pathogenic TPO mutation]. AB - TPO is the key enzyme involved in the thyroid hormone synthesis. The human TPO (hTPO) gene locates on chromosome 2 and consists of 17 exons and 16 introns. Compared with other peroxidases, hTPO is 42% homologous with granulocyte myeloperoxidase. Thyroid cells contain multiple TPO mRNA transcripts of various size. However, the reason is unknown. TTF-1 and TTF-2 are known to regulate TPO gene expression. Moreover, the other factors are becoming clear to regulate it. Congenital TPO defects result in hypothyroidism and goiter. Recent studies clarify a human mutation causing TPO deficiency. PMID- 8196172 TI - [Thyroglobulin (Tg) gene and familial Tg synthesis defect]. AB - The thyroglobulin (Tg) gene is a 300-kilobase (kb) single copy gene, containing at least 42 exons, mapped in man to chromosome 8 (8q24) and codes for a glycoprotein with a molecular weight 660,000, which functions as a matrix for the thyroid hormone (T4, T3) and iodothyronine synthesis. Recent progress in genetic technology enables us to study a family case of hereditary goiter with hypothyroidism due to Tg synthesis defect. RT-PCR and subsequent sequencing of the Tg gene revealed a C to G conversion at -3 position of the acceptor splice site in intron 3. This splice site mutation resulted in exon. 4-deleted (major) and exon 3-5-deleted (minor) mRNAs in the goiter thyroid. This defect in this patient indicates the importance of the tyrosine No. 130, coded within the exon 4, in the thyroid hormone formation. PMID- 8196173 TI - [Cloning of human thyroxine-binding globulin cDNA, isolation of the gene, and its transcriptional regulation]. AB - Cloning of human thyroxine-binding globulin (TBG) cDNA and gene revealed that the primary structure of TBG and its gene organization are homologous to those of serine protease inhibitors (serpin). The transfection study of the TBG promoter linked to chloramphenicol acetyltransferase gene demonstrated that the putative hepatocyte nuclear factor-1 site (located at -77 approximately -65) is required for the transcription of the TBG gene. In addition, the sequence located at -218 approximately -102 is responsible for liver-specific expression of the gene. Estrogen, thyroid hormone and glucocorticoid had little effect on the promoter activity, suggesting that the alteration of serum TBG concentration by these hormones is due to their effect on posttranslational steps in TBG synthesis and secretion. PMID- 8196174 TI - [Inherited abnormality of thyroxine-binding globulin: its gene abnormality and pathogenesis]. AB - Inherited TBG abnormalities manifest complete deficiency (CD), partial deficiency (PD) or excess in blood. Analysis of the TBG gene revealed that all cases with CD and PD studied so far had mutations within the exon. A nucleotide substitution was found in each case of PD and one of three cases of CD. In two other cases of CD, there was a nucleotide deletion. By the transfection study, it was revealed that TBG-CD secretion was completely blocked due to an impaired transport from rough endoplasmic reticulum to Golgi apparatus. The cause of PD is also explained by a partial impairment of TBG secretion. However, a pathogenesis of TBG excess has not been clarified yet. PMID- 8196175 TI - [Thyroxine-binding proteins--familial euthyroid hyperthyroxinemia due to point mutations of transthyretin]. AB - Some of the point mutations in transthyretin (TTR) exhibit increased affinity for thyroxine (T4) and result in euthyroid hyperthyroxinemia in affected individuals. TTR, also known as thyroxine binding prealbumin, is a homotetrameric plasma protein of MW 55,000 that transports 15% of serum T4. The known point mutations that cause euthyroid hyperthyroxinemia are Ala109 (ACC) to Thr (GCC) and Gly6 (GGT) to Ser (AGT). These mutations are transmitted by autosomal dominant inheritance. The laboratory findings are an elevated total T4, an increased free T4 index, a normal free T4, and normal levels of total and free triiodothyronine. The Thr109 mutation abolishes Fnu4HI restriction site, and the Ser6 mutation eliminates the Msp I restriction site. PMID- 8196176 TI - [Molecular cloning and multifunctions of membrane-associated 3,5,3'-triiodo-L thyronine binding protein with protein disulfide isomerase activity]. AB - The protein or cDNA sequencing revealed that the membrane-associated 3,5,3' triiodo-thyronine binding protein (T3BP) acts as a multifunctional protein:protein disulfide isomerase (PDI) catalyzing isomerization of intra- and inter-molecular disulfide bridge in the proteins, beta-subunit of prolyl 4 hydroxylase catalyzing the formation of 4-hydroxyproline in collagen molecules, glycosylation site binding protein which is a component of oligosaccharyl transferase transferring oligosaccharide chains to the asparagine residues of Asn X-Ser/Thr site in nascent polypeptide, and a component of triglyceride transfer protein complex involved in the transfer unit of triglyceride, cholesteryl ester and phosphatidylcholine between biomembranes. The functions of 55 k-T3BP/PDI, mainly involved in important post-translational modifications, are discussed in relation to the domain structure of the molecule. PMID- 8196177 TI - [Regulation of thyroid hormone binding protein/protein disulfide isomerase (T3BP/PDI) gene expression]. AB - PDI catalyzes the formation of disulfide bonds and plays a central role in the correct folding of nascent polypeptides. In addition, it is multifunctional and may participate in more complex enzyme systems, catalyzing other protein modification. PDI is also known to bind T3. The human T3BP/PDI gene, located in the chromosome 17, consists of a transcribed part of 16.5 kb and the protein coding sequence is divided into 11 exons. The analysis of the 5'-flanking region revealed several putative transcriptional elements, including a TATA box, 6 CCAAT elements and 5 GC-rich regions, each of which is related to the promoter activity. The mechanism of T3BP/PDI gene expression is, however, unknown. Treatment with T4, PTU, insulin and fasting-refeeding induced different responses in T3BP/PDI mRNA and protein levels among various tissues. Recent studies revealed that the unfolded proteins, accumulated in the ER lumen, might stimulate the gene expression of a set of protein including BiP, GRp94 and PDI, which is required for proper protein folding and assembling. The meaning of T3-binding activity of PDI is open for further study. PMID- 8196178 TI - [The structural and functional multiplicity of T3 receptor and its gene]. AB - Thyroid hormone receptor (TR) is encoded by the protooncogene c-erb A. There are multiple TR isoforms such as TR beta 1, beta 2, alpha 1, variant alpha 2 and alpha 3. There is also a related gene, Rev-erb A. TR and steroid hormone receptors consist of a superfamily and have a characteristic domain structure including DNA-binding, ligand-binding and dimerization domains. The expression of TR isoforms is tissue and cell type specific and is regulated by development and hormonal status. TR mRNA and protein concentrations do not always correlate. TR beta 2, which exists in the pituitary, may be important for the regulation of TSH secretion. The functional difference of TR alpha 1 and TR beta 1 is still unclear and physiological significance of the TR variants is unknown. PMID- 8196179 TI - [Functional domain structure of thyroid hormone receptor and interaction among T3, T3 receptor and T3RE]. AB - Thyroid hormone receptor is a member of the c-erb A nuclear hormone receptor superfamily. As a ligand dependent transcription factor, it has functions such as ligand binding, DNA binding, transactivation and interaction with other factors. While each of these functions is ascribed to a certain region of the receptor molecule called a domain which can function independently of other domains, these domains cooperate with each other to fulfil the integrated receptor function as a signal transduction apparatus. Characteristics of thyroid hormone receptor which are distinct from those of steroid hormone receptors, such as the role of ligand in receptor function, heterogeneity in TREs, heterodimerization with TRAPs and the dominant negative effect, are described in the context of the integrated receptor function. PMID- 8196180 TI - [Structure and function of TRAP]. AB - Thyroid hormone receptor (THR) binds to specific thyroid hormone response element (TRE). Using an electrophoretic mobility shift assay (gel-shift), Murray and Towel recently found that cell nuclear extracts enhance the binding of THR to TRE. This protein has been designated T3 receptor auxiliary protein (TRAP). Retinoid X receptors (RXR alpha, beta) can function as TRAP. TRAP forms a heterodimer with THR through the ligand binding domain of both receptors. This area contains leucine zipper like heptad repeats which can form amphipathic alpha helixes. The ligand (9-cis retinoic acid) of RXR may or may not synergistically increase T3/THR-mediated transactivation. The effects of 9-cis retinoic acid depends on the nature of the TRE. One of the functions of TRAP may be to alter the expression of T3-regulated genes. PMID- 8196181 TI - [Resistance to thyroid hormone]. AB - Resistance to thyroid hormone (RTH), Refetoff's syndrome, is a syndrome of reduced responsiveness of target tissue to thyroid hormone (TH). Inheritance is usually autosomal dominant except in one family, being recessive. Since a point mutation was first discovered in the thyroid hormone receptor (TR) beta gene of a subject with RTH, approximately 93 unrelated families with RTH have been found to have mutations on TR beta gene. Clinically they presented either generalized (GRTH) or dominantly pituitary (PRTH) resistance to TH. In one family, affected consanguineous individuals lacked the entire protein coding region of both hTR beta alleles. In this family with recessively inherited RTH, the obligate heterozygous parents exhibited no clinical and laboratory abnormalities. Thus, manifestation of RTH in heterozygous individuals required the expression of a mutant receptor that interferes with the function of normal allele ("dominant negative effect"). The formation of mutant TR/TRAP (RXR etc.) heterodimer or mutant TR homodimer having the capability to bind the DNA for this dominant negative suppression of mutant TR beta, and the variation of TRE types, receptor isoforms and auxiliary proteins depending on the target tissue may play an important role in the manifestation of TH resistance. This may explain in part the intra- and inter-individual differences in organ resistance in patients with RTH. Studying the errors of nature would contribute to understand the molecular mechanism of TH action. PMID- 8196182 TI - [Diagnosis of thyroid hormone resistance by molecular biology]. AB - The syndrome of thyroid hormone resistance is an inherited disease characterized by reduced thyroid hormone actions in the tissue. Clinically it is classified into two types: generalized resistance to thyroid hormone (GRTH) and pituitary resistance (PRTH). Recent advances in molecular biology have revealed a number of genetic abnormalities of thyroid hormone receptor beta (TR beta) in this disorder. The mutations of TR beta localized to two "hot spots" in the ligand binding domain. This article describes the basic procedures how to analyze TR beta genes and the functions of mutant TRs. Single stranded conformation polymorphism method is useful for screening and DNA sequencing is important to identify a TR gene mutation in patients. It is also necessary to construct the expression vector containing the mutant TR beta 1 gene to evaluate the mutant receptor functions. PMID- 8196183 TI - [Point mutation of T3 receptor-beta gene and syndrome of inappropriate secretion of TSH]. AB - Thyroid hormone receptors (TRs) are bound to the T3-responsive element of DNA as dimers and heterodimerization with TR-auxiliary protein (TRAP) strongly enhances this binding. In affected members of families with the thyroid hormone resistance syndrome, significant point mutations have been identified in the hormone-binding domain of one of the two alleles of the TR beta gene, especially in two "hot spot" regions, avoiding the regions required for DNA binding, dimerization or binding to TRAP. These findings suggested that DNA-binding and receptor dimerization are important for dominant negative inhibition by the mutant TR, which is responsible for thyroid hormone resistance in a heterozygous patient with a point mutation in the TR beta gene. PMID- 8196184 TI - [Structure and regulation of human thyroid-stimulating hormone (TSH) gene]. AB - This article describes the structure of human thyroid-stimulating hormone (TSH) gene and the regulation of its expression. TSH is a heterodimer composed of common alpha subunit and unique beta subunit encoded by genes located on different chromosomes. It is known that the expression of these subunit genes is regulated in different mechanism by several extracellular factors. The DNA sequencing data of the gene demonstrated that these genes were regulated by interaction of several potential regulatory elements with transcription factors. This transcriptional regulation was analyzed by transient expression of chimeric gene fragments and DNA-protein binding assay, in vitro. To identify the essential DNA regulatory elements of the human TSH beta gene in vivo, we introduced 1.1 kbp of the 5' flanking region of the human TSH beta gene-simian virus 40 T-antigen (SVT) fusion gene into the mouse. This region could direct pituitary-specific expression of SVT and tumorigenesis in transgenic mice. PMID- 8196185 TI - [Molecular genetics of congenital isolated thyrotropin deficiency]. AB - In 1971, the first case of congenital isolated thyrotropin (TSH) deficiency was reported by Miyai et al. Subsequently, the same group reported that the disease was caused by a missense mutation in the CAGYC region of the TSH-beta gene (substitution from G to A in exon 2 which altered the Gly29 [GGA] to Arg29 [AGA]). At present the same mutation was reported in 6 patients in 5 Japanese families. Dacou-Voutetakis reported 3 patients with a nonsense mutation in exon 2 (Glu12 [GAA] to Ter [TAA]) and Rajan reported 3 patients with bioinactive TSH caused by a frameshift mutation in exon 3 (Cys105 [TGT] to Val105 [*GTA] and Val114 [GTA] to Ter [TAG]). Significance of C-X-G-X-C motif for biosynthesis of glycoprotein hormones and mass screening for early diagnosis of this disease were discussed. PMID- 8196186 TI - [Pituitary specific transcription factor Pit-1/GHF-1 and combined pituitary hormone deficiency]. AB - Pit-1/GHF-1 is a pituitary-specific POU-domain DNA binding factor, which binds to, and trans-activates the promoters of both growth hormone (GH) and prolactin (PRL) genes. It is well conserved among vertebrates and is indispensable for both differentiation and proliferation of the somatotrophs, lactotrophs and thyrotrophs. PIT1 abnormality is defined as a genetic abnormality in the PIT1 gene, and results in various types of combined deficiencies of thyrotropin (TSH), GH, and PRL. PIT1 abnormality was first recognized as an excellent model for 'transcription factor disease'. Recently, we found a novel case whose cannot be explained by the PIT1 gene mutation alone. Such case will give us precious clue to identify modifier factors of Pit-1/GHF-1. PMID- 8196187 TI - [Structure and function of the promoter region of the TSH receptor gene]. AB - TSH receptor (TSHR) is expressed almost exclusively in thyroid cells. The rat TSHR gene has a TATA-less, GC-rich promoter, with multiple transcriptional start sites. The minimal promoter region, sufficient for the basal promoter activity, thyroid-specific expression and negative regulation by TSH/cAMP signal, is located between -195 and -39 bp relative to the ATG start codon, and is highly conserved in the rat and human genes. This region comprises three important elements. First, a cAMP response element (CRE), which functions as a constitutive enhancer essential for the basal promoter activity. Second, tandem repeat sequences just 5' to the CRE, which are recognized by two distinct ssDNA-binding proteins. This element suppresses the function of the CRE, thus repressing the promoter activity. Third, a binding site for the thyroid-specific transcription factor TTF-1, which dictates thyroid-specific expression and negative regulation by TSH/cAMP of the gene. Thus, the expression of the TSHR gene is exquisitely regulated by these multiple factors in thyroid and non-thyroid cells. PMID- 8196188 TI - [Thyrotropin receptor is expressed in non-thyroid tissues]. AB - We have obtained TSH-R cDNA fragments from rat retro-orbital tissues and adipose tissue as well as FRTL5 cells by polymerase chain reaction methods. Nucleotide sequence of the non-thyroid cDNA was identical to that of the thyroid. Northern blot analysis has revealed that extremely high amount of TSH-R mRNA exist in the adipose tissue. TSH-R peptide antibody produced in rabbit, which stained recombinant TSH-R as 104 and 100 kDa proteins, also recognized the same M.W. bands in the adipose tissue and the retro-orbital tissues. These results suggest that TSH-R is expressed even in non-thyroid tissues. PMID- 8196189 TI - [An alternatively spliced form of the human thyrotropin receptor transcript]. AB - An alternatively spliced form of the human thyrotropin receptor (hTSHR) mRNA transcript, which has previously been detected on Northern blot analysis of human thyroid cells, was cloned. The smaller hTSHR cDNA, designated hTSHR cDNA-I, is approximately 1 kb in size and encodes a protein of 253 amino acids. Comparison of the nucleotide sequence of hTSHR cDNA-I with available hTSHR genomic sequence data reveals that the cDNA-I contains exons 1-8 and an unidentified DNA tract, presumably an intron. Thus, the hTSHR cDNA-I encodes the N-terminal half of the extracellular domain of the hTSHR (approximately 60%). The truncated TSHR-I may be secreted and function as a TSH binding protein. PMID- 8196190 TI - [Domain structure and signal transduction mechanisms in the thyrotropin receptor]. AB - The thyrotropin receptor is a single polypeptide (744 amino acids) consisting of two domains (N-terminal extracellular domain and C-terminal transmembrane/cytoplasmic region). The former (398 aa) contains six potential glycosylation sites, 11 cysteins and 9 leucine rich repeats and is very likely to be the major TSH binding site. On the other hand, the latter (346 aa) has a characteristic of G protein coupled receptors (seven transmembrane segments, 3 extracellular-and cyto-plasmic loops and a carboxyl terminal tail), contains potential phosphorylation sites (serine/threonine residues) for c-kinase and G protein coupled receptor kinase and plays important roles in signal transduction and homologous desensitization. Experimentally-produced and naturally-occurring mutant receptors provide molecular mechanisms of receptor function. PMID- 8196191 TI - [Signal transduction of the thyrotropin receptor]. AB - The thyrotropin receptor (TSHR) mediates dual signalling, cAMP and phosphoinositide (PIP2) responses. We have characterized the roles of the 2nd and 3rd cytoplasmic loops on signal transduction by site-directed mutagenesis. Middle portion in the 2nd loop (residues 525-527) is found to be important for Gs coupling. On the other hand, N- and C-terminal regions of the 3rd loop and residues 528-532 in the 2nd loop are important for Gq coupling. Further, mutations involving residue 617-620 in the 3rd loop result in constitutive activation. Constitutively activating mutations of the TSHR and LH/CGR (lutropin/choriogonadotropin receptor) are found in functional thyroid adenoma and familial male precocious puberty, respectively, and appear to be the direct cause of each disease. PMID- 8196192 TI - [The structure and function of the extracellular domain of human thyrotropin receptor]. AB - Since the molecular cloning of human TSH receptor (TSHR), much efforts have been focused on determining the TSH or TSAb binding sites. Despite many conflicting data, there seems to be a consensus that TSH binds to the various parts of the extracellular domain of TSHR discontinuously. However, following questions are not yet answered 1) Is the binding to extracellular domain of TSHR sufficient to the signal transduction? 2) Is there any contribution of the extracellular loops to TSH binding? Using TSHR mutated at the first or the second extracellular loops, we propose that the extracellular loops are important for TSH binding and signal transduction. PMID- 8196193 TI - [Molecular cloning and posttranslational processing of human preprothyrotropin releasing hormone]. AB - Human PreproTRH gene and its hypothalamic cDNA were cloned. The human preproTRH protein contains six copies of TRH progenitor sequence flanked by paired basic amino acids. Radioimmunoassays with specific antibodies raised against five human preproTRH cryptic peptides and chromatographic analyses identified that the posttranslational processing of preproTRH in hypothalami and placentae could be different. Moreover, transfection assays using human preproTRH promoter luciferase chimeric-plasmids demonstrated that human preproTRH promoter activities were regulated negatively by T3 in GH3 cells. Cloning of the human preproTRH gene would facilitate the elucidation of the molecular mechanism of actions of TRH and TRH cryptic peptides in human hypothalamo-pituitary-thyroid axis and central nervous system. PMID- 8196194 TI - [Clinicopathological and diagnostic study of mucin producing pancreatic tumors]. AB - A total of 80 cases (40 operated cases and 40 follow-up cases) of mucin producing tumor (MPT) of the pancreas was studied to elucidate its clinicopathologic characteristics and assess therapeutic strategy. This disease was encountered histologically in various such as hyperplasia and carcinoma with invasion. 75% of carcinoma cases of branch duct type were accompanied by intraductal spread to the main duct and most of those cases had intraductal extension of less than 5mm in length to the main duct. Multicentricity was found in 28.6% of carcinoma cases. Parenchymal invasion was observed in 28.6% of carcinoma cases and lymph node involvement was seen in one case. Thus, prognosis of the patients with MPT was better than that with "common" duct cell carcinoma of the pancreas. Among diagnostic modalities, Selective ERP and EUS were useful especially in demonstrating precise pancreatograms and excrescent nodules. For histocytologic diagnosis prior surgery, EPB proved very useful in combination with pancreatic juice cytology. PMID- 8196195 TI - [A case of eosinophilic gastroenteritis with ulcerative lesion at the upper body of the stomach]. PMID- 8196196 TI - [An adult case of ileo-cecal intestinal duplication associated with intussusception, which is difficult to be differentiated from submucosal tumor]. PMID- 8196197 TI - [A case of ruptured multiple mesenteric varices successfully treated by transjugular intrahepatic portosystemic stent shunt (TIPSS)]. PMID- 8196198 TI - [A case of postoperative cutaneointestinal fistula responding to somatostatin analog, with a special reference to serum level of gastrointestinal hormones]. PMID- 8196199 TI - [A case of biliary cystadenocarcinoma communicating with the bile ducts]. PMID- 8196200 TI - [Hepatocellular carcinoma in patient with primary biliary cirrhosis]. PMID- 8196201 TI - [A case report of multiple hepatic hilar cyst associated with hepatocellular carcinoma]. PMID- 8196202 TI - [A case of autoimmune cholangitis with rheumatoid arthritis]. PMID- 8196203 TI - [A case of inflammatory polyp of the gallbladder which was difficult to differentiate from cancer]. PMID- 8196204 TI - [A case of descending colon stenosis associated with acute pancreatitis]. PMID- 8196205 TI - [Treatment of severe acute pancreatitis]. PMID- 8196206 TI - [Immunohistochemical study of Helicobacter pylori and mononuclear cells in the gastric mucosa of patients with gastritis or peptic ulcer]. AB - The distribution and localization of Helicobacter pylori (HP) and mononuclear cells (MNC) in the gastric mucosa were investigated immunohistochemically in 120 patients with gastritis or peptic ulcer. HP was detected in the gastric mucosa of 58% of 40 gastritis patients, 82% of 56 gastric ulcer (GU) patients, and 88% of 24 duodenal ulcer (DU) patients. In the HP-positive mucosa, cells positive for IgG or IgA were increased significantly when compared to the HP-negative mucosa. Neutrophils and eosinophils were also increased under the HP-infected surface and therefore these cells were likely involved in the mucosal damage. Enhancement of the expression of HLA-DR antigen was observed in the gastric epithelium with HP infection and it was associated with a significant increase of lymphoid follicles and B cells in the mucosa. In comparison with the HP-infected mucosa of gastritis patients, the number of MNC were increased significantly in the mucosa of both DU and GU patients. The number of HP in the gastric mucosa of DU patients was significantly higher than those of both gastritis and GU patients. In addition, the grade of the infiltration of MNC and IgA positive cells were always greater in DU than in gastritis, regardless of the number of HP. These findings suggested that activation of the local immunity in the gastric mucosa of gastritis and peptic ulcer patients by HP infection may participate in the pathogenesis of gastroduodenal mucosa damage. PMID- 8196207 TI - [A study of the influence of gastric acid on the extension of regenerative epithelium of gastric ulcer]. AB - To study the influence of gastric acid on the extension of the regenerative epithelium, 26 patients (28 ulcers) of gastric ulcer were examined by the stereo video-endoscope being able to measure the length and 24-hours intragastric pH monitoring. Extending speeds of the regenerative epithelium were measured from the time the regenerative epithelium of the ulcer was observed till the last examination, but which was limited 8 weeks after the first observation of the regenerative epithelium. The relationship was not observed between the extending speeds and the stages (A2-H1, H1-H2, H2-S1) of the ulcer. For 21 ulcers followed up by the stereo video-endoscope from active stage, the extending speed of the regenerative epithelium and the pH 3 holding time in a day were significantly correlated (r = 0.51, p = 0.014), and the same relationship (r = 0.56, p = 0.008) were observed in the nighttime. It was confirmed that the gastric acid regulated strongly the extending speed of regenerative epithelium of gastric ulcer. The intragastric circumstance of the low acid secretion induced by the antacid-drugs was considered to accelerate the extension of regenerative gastric epithelium. PMID- 8196208 TI - [Deterioration of liver function following endoscopic injection sclerotherapy of esophageal varices--significance of the new liver function test "intravariceal injection (I.I.) index"]. AB - Changes of liver functions associated with endoscopic injection sclerotherapy (EIS) were investigated in 143 patients with remarkable esophageal varices. The index used for evaluating hepatic reserve was the ratio between the increase of total bilirubin and the increase of LDH after EIS [I.I. index = (delta T.Bil./delta LDH) x 100] in cases treated by intravariceal injection of 5% ethanolamine oleate. I.I. index value caused by hemolysis was stable and always below 0.2, while the elevation of I.I. index above 0.2 was regarded as the reflection of the deterioration of liver function. After the entire sessions of EIS, the changes of liver function tests before and after EIS were estimated in 104 cases using 3 factors as follows; (1) delta T.Bil.; increase of total bilirubin more than 0.5 mg/dl (2) delta PT; decrease of prothrombin time more than 5% (3) delta ICG R15; increase of ICG R15 more than 5%. I.I. index of group I (without any changes of 3 factors mentioned above; n = 66) was 0.22 +/- 0.16, approximately within normal range. However, in group II (with 1 factor; n = 29), group III (with 2 factors; n = 5), group IV (with all factors; n = 4), I.I. index was elevated according to the severity of their liver dysfunction. The cases whose I.I. index value increased gradually during the course of EIS, were apt to deteriorate the liver functions and therefore, should be carefully observed. Also, I.I. index seems to reflect the prognosis of the patients treated by EIS for some extent, since the survival period of the cases treated by EIS were correlative with the value of I.I. index (r = -0.542, p < 0.01), and I.I. index of 32 cases who survived for longer than 5 years after EIS was almost normal (0.22 +/- 0.15). PMID- 8196209 TI - [Recommendations for preventing transmission of infection with biohazard in the practice of legal medicine (2). Equipment and practical applications. The Medico Legal Society of Japan, Committee on Expert Opinions]. AB - In May, 1993, our committee of the Medico-Legal society of Japan published an article entitled "Recommendations for Preventing Transmission of Infection with Biohazard in the Practice of Legal Medicine" in The Japanese Journal of Legal Medicine. Concerning this article, we received a lot of useful comments and opinions from many members of the society, for which we are very grateful. We also received a lot of requests for further information concerning details on the equipment and its practical applications. Since a lot of departments of Legal Medicine at several universities throughout Japan at present are remodelling their facilities in order to be able to perform autopsies, with respect to such circumstances, our committee felt the need to provide information on basic conditions concerning the prevention of transmission of infections with hazards. PMID- 8196210 TI - MRI and MRS studies on acute effects of ethanol in the rat brain. AB - Magnetic resonance imaging and spectroscopy (MRI and MRS) were used to examine the effects of intoxicating doses of ethanol on the rat brain. 1H-MR images were obtained using three different methods: (1) PD weighted images, (2) T1 weighted images and (3) T2 weighted images. T1 and T2 relaxation times of the tissues were calculated by pixel-to-pixel image computation. After ethanol treatment, the cerebral hemispheres showed high signal intensities in the T1 weighted images, whereas low signal intensities were observed in the T2 weighted images, markedly in the cortex. At 4 h, the T1 values significantly decreased in the thalamus and the hypothalamus of the ethanol treated rats compared with those of the animals under pentobarbital anesthesia. At 1 h, the T2 values significantly decreased in the cortex of the ethanol treated rats. At 4 and 24 h, the T2 values significantly decreased throughout the cerebral hemispheres in the ethanol treated rats. The in vivo 31P-MRS results showed that after ethanol treatment, ATP and phosphocreatine slightly decreased, but not to a great degree. Intracellular pH levels, determined using the values of the chemical shift in inorganic phosphate peaks, decreased and returned to normal by 4 h. In the highly sedated animals, the acidosis observed early on was followed by heavy alkalosis. In in vitro 1H-MR spectra of brain and blood extract samples, many kinds of metabolites were assigned. The quantitative results were as follows: (1) Blood and brain ethanol levels rose to a peak at 1 h after ethanol treatment and no ethanol was detected at 24 h in any samples. (2) Blood acetate levels increased significantly, and returned to the control level by 24 h, whereas the brain acetate levels were largely unchanged. (3) Blood lactate levels decreased significantly at 0.5 h and brain lactate levels mildly increased and rose to a peak at 2 h. (4) Brain N-acetylaspartic acid (NAA) increased at 0.5 h significantly and decreased significantly at 4 h. Electron microscopic findings were as follows: (1) Both neuronal and glial cells were edematous after ethanol treatment. (2) Congestion was serious in all the regions we observed, and it was still present 24 h after ethanol treatment. (3) Swelling of mitochondria was observed in capillary endothelial cells. Our results suggest that high doses of ethanol cause circulatory disorders in the rat brain and disturb the water balance in the cerebral tissues, changing the structures of intracellular water molecules. It also causes metabolic confusion without depletion of high energy phosphate metabolites. PMID- 8196211 TI - Pharmacokinetics and postmortem changes of cimetidine in body tissues. AB - Cimetidine concentrations in body tissues were pharmacokinetically examined, together with their postmortem changes, to assess the toxicological effect of this drug from the aspect of forensic medicine. For the pharmacokinetic study, rats were pithed at 0.5, 1.0, 2.0, 4.0 or 8.0 hours after an intravenous injection of the drug (33.3 mg/kg), and their tissue samples were immediately collected to be analyzed by high-performance liquid chromatography (HPLC). The concentrations of cimetidine in the blood and muscle decreased below the lower detection limit at 8 hours after the injection, while the drug could still be detected in the brain, lung, liver, kidney, spleen and adipose tissue. The ratios of the cimetidine concentrations in the muscle, lung and spleen to that in the blood were nearly constant until 4 hours after the injection, while those in the liver, kidney and adipose tissue increased as time elapsed. Postmortem changes of cimetidine concentrations were examined using the tissue samples collected 0, 1 and 2 days after death. There was no statistical significance in the postmortem changes in cimetidine concentrations in the body tissues over the two-day period of examination. The experimental results indicated that the muscle, lung and spleen together can serve as samples for toxicological analysis to evaluate the effect of cimetidine, regardless of various postmortem factors, including the availability of blood. PMID- 8196212 TI - [Experimental exposure to carbon monoxide in rats (II)--blood volume of organs obtained by calculations from amounts of carbon monoxide in organ tissues and in blood]. AB - We have found a correlation between the degree of carboxyhemoglobin saturation and the amount of carbon monoxide (CO) in the organ tissues of rats. This essay is titled "Experimental exposure to carbon monoxide in rats (I)". In this report, the blood volumes in organs were calculated from the amount of CO in the blood and in the organ tissues of the same rat. The obtained blood volume (microliter/g of organ tissues) were as follows: spleen 0.196 +/- 0.0222 liver 0.186 +/- 0.0576, lung 0.166 +/- 0.0156, myocardium 0.095 +/- 0.0319, kidney 0.094 +/- 0.0267 and encephalon 0.033 +/- 0.0183. Except for the 10% COHb experimental group, it has become clear that the blood volume in the spleen and in the kidney did not change much despite the variation of degree of carboxyhemoglobin saturation. In order to diagnose the cause of death of a burned cadaver in which the heart did not contain the liquid blood, values of CO amounts should be determined from those in the spleen or the kidney. PMID- 8196213 TI - Personal identification from human remains using morphological characteristics and DNA analysis. AB - This report describes personal identification of four parts of a dismembered human body on the basis of physical characteristics and DNA analysis. A 69-year old woman suffering from depression went missing from her home in May 1992. Five days after her disappearance, a female torso was found in a river. In a two-week period thereafter, a left forearm, a female head and neck and a right forearm were found consecutively in the same river. Although the end of the cervical vertebra was anatomically identical to that of the torso, the two forearms did not match. However, DNA analyses with a single-locus DNA probe pYNH24, DO alpha typing and a multi-locus DNA probe "Myo", indicated that these four parts came from the same person. The missing woman had undergone lobectomy of the right pulmonary upper lobe, and had suffered from slight scoliosis of the thoracic vertebrae and a second lumbar vertebral compression fracture. These characteristics were also observed in the torso. In order to obtain more conclusive evidence, DNA fingerprinting using DNA extracted from the torso, the missing woman's brother and her daughter was performed using the DNA probes described above. The data obtained indicated that the remains were those of the missing woman. PMID- 8196214 TI - A groove observed in the face of an old man who probably died from acute asphyxia. AB - A continuous, horizontal groove about 0.7 cm wide was observed on the nape and lower part of the face of a 93-year-old man. The groove started from one corner of the mouth, traversed the nape, and reached the other corner of the mouth. It was most conspicuous at the nape. The mark was considered to have been produced by an electric cord. No facial congestion was noted, however, a few petechiae were present in the conjunctivae. There were no wounds in the front of the neck, while small hemorrhages were noted in the neck muscles. The right 2nd through 6th ribs were fractured and slight hemorrhage was observed in the overlying muscle. There were no pathologic changes accounting for death. The presence of the so called triad for an acute death suggested strongly that the most likely cause of death was acute asphyxia. The relationship between the cause of death and the mark was the matter at issue. The mark may have been produced by a hanging in an unusual position, but there was no indication that a hanging was performed. For a ligature mark due to strangulation, the level was too high. The possibility that the mark was produced when the victim was gagged seemed to be very low. Thus, it could not be confirmed whether the groove had any relation with a fatal assault. Reflex cardiac arrest by vagal stimulation when the neck was compressed was the most likely cause of death. PMID- 8196215 TI - [Case of death by fire with kerosene--analysis of contents of trachea and stomach]. AB - In death caused by fuel oil burning, it's difficult to examine the vital reaction in the burning skin surface. In these cases, in stead of skin examination, we've been determining the fuel oil in blood. In this case, besides this method, we tried to examine the contents of the trachea of a person who died of kerosene oil burns. CASE: A 49-year-old female was found dead in a cabin. Burns on her body ranged from first to fourth-degree, and 91% of the body was charred. Carbon particles were detected within the trachea and the bronchus, and were slightly detected in the gastric contents and the esophagus. Carboxyhemoglobin concentration was found to be 21% in the right heart blood and 22% in the left heart blood. The level of cyanide detected was 4.3 microM in the right heart blood and 1.7 microM in the left heart blood. Ethanol was not detected in either sample. Kerosene components were detected in each sample (blood, trachea content, gastric content and body surface). According to the formulation of kerosene components, results of contents of the trachea were most likely from a kerosene on the market. In the blood, many volatile paraffin hydrocarbons were found, and, on the body surface, many high boiling-point paraffin hydrocarbons were detected. The means that values of detected kerosene formulation from the blood and trachea contents were similar to types of kerosene on the market. From these results, we concluded that the victim inhaled kerosene vapor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196216 TI - [Effects of rHuEPO on cellular proliferation and endothelin-1 production in cultured endothelial cells]. AB - To elucidate the effects of recombinant human erythropoietin (rHuEPO) on endothelial cell proliferation, protein synthesis and endothelin-1 (ET) production by endothelial cells were examined in a cultured endothelial cell (EC) system. EC, incubated with various concentrations of rHuEPO (0, 1000, 5000, 10,000mU/ml) for up to 3 days exhibited dose-dependent cellular proliferation that could be inhibited by anti-rHuEPO rabbit antiserum. DNA and protein synthesis, measured by the uptake of 3H-thymidine and 3H-leucine, respectively, showed dose-dependent increases after incubation of confluent EC in the resting phase of the cell cycle with various concentrations of rHuEPO (0, 1000, 2500, 5000, 10,000mU/ml) for 18 h. After an additional 6-h culture with rHuEPO at 5000mU/ml or more, the supernatant concentrations of immunoreactive ET showed significantly greater values than those without rHuEPO. Furthermore, rHuEPO increased the DNA synthesis by EC, which had been cultured in E-BM medium containing 0.5% or 2% FBS for 3 h, and which were recultured in E-BM medium containing 5% FBS or containing 2% FBS with 10 ng/ml EGF for 15 h. These results suggest that rHuEPO directly stimulates EC proliferation as a competence factor, and also accelerates endothelin-1 production in association with stimulation of DNA and protein synthesis by EC. PMID- 8196217 TI - [Role of endothelium-derived nitric oxide in mediating the natriuretic response to acute extracellular volume expansion]. AB - To determine the role of endothelium-derived nitric oxide (EDNO) in mediating the natriuretic response to acute extracellular volume expansion (ECVE) with isotonic saline (3% of body weight per hour), the diuretic and natriuretic responses to ECVE were studied in anesthetized Sprague-Dawley rats during the intravenous infusion of an EDNO synthesis inhibitor, NW-nitro-L-arginine methyl ester (L NAME). Intravenous infusion of L-NAME at the dose of 5 micrograms/kg/min significantly inhibited the diuresis and natriuresis in response to ECVE by 58% and 67%, without altering arterial pressure, effective renal plasma flow, glomerular filtration rate and basal excretory function. This inhibitory effect of L-NAME on the diuretic and natriuretic responses to ECVE was attenuated by the infusion of the EDNO synthesis precursor, L-arginine (1mg/kg/min), but not by D arginine. In addition, pretreatment with 0.3 mg/kg of the angiotensin II receptor antagonist, L-158,809, normalized the diuretic and natriuretic responses to ECVE in L-NAME-treated rats, suggesting an angiotensin-II-dependency of the reduced renal excretory response to ECVE during EDNO synthesis inhibition. Neither L arginine nor L-158,809 alone significantly altered the renal excretory response to ECVE compared with vehicle-treated control rats. These results suggest that EDNO might play an important role in the regulation of sodium and water excretion during ECVE, and indicate a possible interaction between EDNO and angiotensin II on the renal excretory function. PMID- 8196218 TI - [Assessment of the distribution of renal cortical blood flow by contrast ultrasonography]. AB - The importance of the distribution of intrarenal blood flow in the regulation of various renal functions, such as urine concentration and sodium excretion, has been well recognized. However, there have been no reliable methods to measure local flow in the kidney in vivo. The present study demonstrated the usefulness of contrast ultrasonography combined with injection of sonicated 5% albumin for assessment of the distribution of renal cortical blood flow in eleven mongrel dogs. The left kidney was displayed by tomographic echography, and microbubbles of sonicated albumin were injected into the abdominal aorta above the left renal artery. Video density time curves were generated and fitted to a time-intensity curve. Intrarenal infusion of acetylcholine (4.0 micrograms/kg/min) increased renal blood flow (RBF) from 2.5 +/- 0.3 to 4.6 +/- 1.0 ml/min/g kwt (p < 0.01), and norepinephrine (0.5 microgram/kg/min) decreased RBF from 2.5 +/- 0.3 to 1.2 +/- 0.5 ml/min/g kwt (p < 0.01). There were significant positive correlations between percent change in RBF and peak intensity and area under the curve, which were calculated with a time-intensity curve. Furthermore, the inner/outer renal cortex ratio of peak intensity significantly increased during acetylcholine infusion (0.72 +/- 0.11 vs 0.86 +/- 0.09; p < 0.01), whereas no significant change was observed during norepinephrine infusion. These results suggest that renal contrast ultrasonography may be useful for real-time assessment of the distribution of renal cortical blood flow in vivo. PMID- 8196219 TI - [Effect of salt restriction on preeclampsia]. AB - The indication of low salt diet for the management of hypertension associated with pregnancy is controversial. We studied the effect of a low-salt diet (less than 5g/day) on pregnancy-induced hypertension compared to patients with hypertension due to chronic renal failure and essential hypertension. In chronic renal failure, mean blood pressure decreased from 115.3 +/- 3.0mmHg to 92.1 +/- 2.6mmHg (p < 0.001) and in essential hypertension, from 117.7 +/- 3.1mmHg to 108.5 +/- 3.5mmHg (p < 0.01). However, in pregnancy-induced hypertension, the blood pressure did not change significantly. CUA/Ccr ratio, the indicator of plasma volume, decreased significantly from 8.7 +/- 1.5% to 3.8 +/- 0.7% (p < 0.001) after salt restriction. CUA and mean blood pressure in patients with preeclampsia were negatively correlated significantly (r = -0.51, p < 0.05). There was a significant correlation between CUA and urinary sodium excretion (r = 0.67, p < 0.001). These results indicate that a low-salt diet is not only ineffective, but also accelerates volume depletion in preeclampsia. PMID- 8196220 TI - [Effects of manidipine hydrochloride on renal function in renal parenchymal hypertensive patients]. AB - The incidence of renal parenchymal hypertension is highest in patients with secondary hypertension. It is important to prevent the progression of renal dysfunction by appropriate treatment, especially by means of antihypertensive drugs. Calcium channel blockers are considered to have the advantage as antihypertensive drugs of maintaining the renal blood flow, even though the perfusion pressure may be decreased. However, these drugs can involve the risk of deteriorating the glomerular function due to hyperfiltration. To investigate whether calcium channel blockers can prevent the deterioration of renal function in renal parenchymal hypertensive patients, we administered manidipine hydrochloride (20 mg, once a day, 24 weeks) to 16 outpatients and evaluated its effects on blood pressure and renal function. The following results were obtained. (1) The systolic and diastolic pressure decreased from 2 and 4 weeks after administration, respectively. A stable antihypertensive effect appeared thereafter and no change was observed in the pulse rate. (2) The renal vascular resistance tended to decrease slightly. The glomerular filtration rate and renal blood flow did not change in spite of the decreased perfusion pressure. (3) No changes were seen in urinary protein, endocrine factors and cardiac function. (4) In some of the cases with decreased GFR (< 70ml/min), the drug could not prevent deterioration of the renal function and did not produce an antihypertensive effect. PMID- 8196221 TI - [Pharmacokinetic study of ofloxacin using saliva concentration in chronic renal failure]. AB - We evaluated saliva concentration as a parameter of therapeutic drug monitoring (TDM) of Ofloxacin (OFLX) in patients with severe renal failure (CRF). Saliva OFLX concentration correlated closely with serum OFLX concentration as shown in healthy subjects, although it was significantly lower (about three-quarters), indicating that OFLX had less penetration into saliva in patients with renal failure. Saliva concentration was almost equal to serum concentration during hemodialysis, which might have been due to the constant dialysis of OFLX. In conclusion, saliva concentration was useful for TDM of OFLX in patients with CRF, as it is in healthy subjects. PMID- 8196222 TI - [Effect of recombinant human erythropoietin on cytosolic free calcium concentration in platelets]. AB - Intracellular free calcium concentration ([Ca2+]i) was examined in the platelets of 15 control subjects (NT), 6 predialysis patients with chronic renal failure (CRF), 17 patients on hemodialysis (HD), 20 patients on continuous ambulatory peritoneal dialysis (CAPD), 10 normotensive persons with genetic hypertension (GHT) and 8 essential hypertensive patients (EHT). Levels of [Ca2+] i in the platelets were measured by the fluorescent calcium indicator Fura-2. Resting [Ca2+] i in CRF and HD patients was higher than the value in NT and that in CAPD patients was similar to NT. rHuEPO significantly increased the level of [Ca2+] i in CRF and HD patients compared to those in NT. Under resting and EPO-stimulated conditions, the levels of [Ca2+] i in GHT and EHT were higher than those in NT. rHuEPO increased the levels of [Ca2+] i in the absence of extracellular calcium in NT, GHT and EHT. In addition, EPO-stimulated calcium influx in GHT and EHT was greater than that in NT. Thus, it appears that the mechanism of rHuEPO-induced hypertension may be mainly due to elevation of [Ca2+] i. EPO may contribute to the development of genetic hypertension. PMID- 8196223 TI - [Prognosis and changes of peritoneal function in CAPD and APD patients]. AB - Prevention of peritoneal function is a major critical factor in the continuation of CAPD treatment. Eighty-nine CAPD and APD patients were investigated for 7 years or 9 months, respectively. The purpose of the present study was (a) to determine the levels of solute in the blood, i.e. serum creatinine (s-Cr), BUN, hANP, Lp (a) and electrolytes, and urinary volume, water removal and dextrose contents in the dialysate, and (b) to analyze these parameters according to categories such as sex, age, presence of DM and frequency of peritonitis in such patients. Peritoneal function of 15 APD patients was also examined by peritoneal equilibration test (PET) and urea kinetics. Excretion of urine in female CAPD patients was higher than that in male patients. The levels of BUN and s-Cr in male CAPD patients increased gradually during the clinical course due to systemic muscular volume and/or loss of urinary excretion. Although there were no significant changes in the levels of solute in the blood between the ages of more or less than 65 years of CAPD patients, the residual renal function rapidly declined in patients more than 65 years of age. CAPD patients who had DM showed a rapid decline in urinary volume, and an increase in Lp(a) and ultrafiltration. The patients who had a frequent episode of peritonitis showed a decrease in water removal with increase in the concentration of dextrose in dialysate. There was a significant correlation between the levels of Ccr and those of KT/V in APD patients after the correction of KT/V with dwell time of dialysate storage in the abdominal cavity. It appears that several factors, such as sex, age, presence of DM and frequency of peritonitis, may be important factors in the maintenance of CAPD for long periods. PMID- 8196224 TI - [A case of oligomeganephronia--quantitative measurement of the glomerular surface area and the number of glomeruli with a color image analyzer]. AB - We report here a nine-year-old boy with oligomeganephronia. The patient had proteinuria and morphometric analysis of the renal biopsy specimen confirmed the diagnosis of oligomeganephronia. We employed a color image analyzer (OLYMPUS Corp.) to determine the glomerular surface area and the number of glomeruli per mm2 of the renal cortex of the patient. All the scanned glomeruli showed marked hypertrophy; the mean maximal surface area for the 5 glomeruli was 46 x 10(3) microns 2, which is approximately 4 times larger than that of normal children of the same age. The number of glomeruli per mm2 of the renal cortex of the patient had decreased to 1. 11 per mm2, which is approximately one fourth that of normal controls with IgA glomerulonephritis. The color image analyzer proved to be useful for the diagnosis of oligomeganephronia enabling the quantitative measurement of the glomerular surface area and the number of glomeruli per mm2 of the renal cortex. PMID- 8196225 TI - [A case of renal hypouricemia associated with IgA nephropathy--with special reference to changes in serum uric acid and uric acid clearance in a clinical course exceeding 15 years]. AB - We report a case of IgA nephropathy associated with renal hypouricemia. The patient's renal function had decreased gradually during the previous 15 years, resulting in chronic renal failure. Levels of serum uric acid and uric acid clearance were 1.0 mg/dl and 39.4 ml/min, respectively. Pyrazinamide suppression test indicated that the patient had defective tubular reabsorption of uric acid at the presecretory site. The serum uric acid level elevated linearly to 5.0 mg/dl during the 15-year period, in parallel with a change in serum creatinine level, giving a significantly positive correlation coefficient of 0.9776. The ratio of uric acid and creatinine clearances showed no significant change, although both decreased during the 15 years. These results were a different from those in patients with chronic glomerulonephritis, including IgA nephropathy, where the serum uric acid level had shown no significant correlation with serum creatinine level above 2.0 mg/dl and the ratio of uric acid clearance and creatinine clearance had exponentially elevated after the latter decreased below 30-40 ml/min. The patient presented here has defective tubular transport of uric acid at the site of urate reabsorption, and appears to show a different tubular dysfunction response from patients with chronic glomerulonephritis and decreased renal function. PMID- 8196226 TI - [A case of membranoproliferative glomerulonephritis due to type II cryoglobulinemia probably associated with hepatitis C virus infection]. AB - In recent years, several laboratories have suggested that chronic hepatitis C virus (HCV) infection is strongly associated with type II cryoglobulinemia (CG) and/or membranoproliferative glomerulonephritis (MPGN). We report here a case of MPGN due to type II CG probably associated with chronic HCV infection, and discuss the pathogenesis and treatment of such cases. A 60-year-old-female was referred to us from a local hospital because of progressive peripheral edema, purpura on the lower limbs, pleural effusion, ascites, hypertension, and renal failure. Laboratory findings indicated proteinuria, abnormal urinary sediments, normochromic normocytic anemia and azotemia. Other laboratory findings included positive rheumatoid factor, elevated serum IgM, hypocomplementemia and elevated circulating immune complexes. Cryoglobulin was detected and found to consist of a mixture of a monoclonal IgM kappa with polyclonal IgG. Renal biopsy showed MPGN. These observations suggested a close association between MPGN and type II CG. We did not find any causes of type II CG except for positive HCV antibody and HCV RNA. Therefore, we made the diagnosis of type II CG associated with chronic HCV infection. Symptoms related to CG was responsiveness to steroid, but development of liver dysfunction developed. Treatment with alfa-interferon (alpha IFN) was added and thereafter, the liver dysfunction improved. However, the serum Cryo level was not reproducibly lowered. While in this case it was unclear whether IFN therapy was beneficial, several reports in addition to the findings of this case suggest a close relation between HCV infection and type II CG and MPGN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196227 TI - [Evaluation of myocardial perfusion and ventricular shape in hypertrophic cardiomyopathy using 99mTc-tetrofosmin scintigraphy: comparison with 201Tl myocardial scintigraphy]. AB - Hypertrophic cardiomyopathy (HCM) is known to have the impairment of myocardial perfusion as well as irregularly hypertrophic myocardium. To evaluate myocardial perfusion and ventricular shape in HCM, 99mTc-Tetrofosmin scintigraphy was performed after exercise (Ex) and at resting state (Re) in 10 patients with HCM and was compared with early image (Ea) and delayed image (De) of 201Tl scintigraphy performed after exercise. SPECT images of both 99mTc-Tetrofosmin and 201Tl scintigraphy were analyzed with five scaled visual scores set in 18 segments. The complete concordance ratio between 99mTc-Tetrofosmin (Ex and Re) and 201Tl (Ea and De) images in segmental analysis was 75%. Image quality of 99mTc-Tetrofosmin was seemed to be superior to that of 201Tl scintigraphy. In 9 patients with HCM, 99mTc-Tetrofosmin scintigraphy was performed under the ECG gating and the thickness of septal and free wall was measured. Good correlation was observed with the data by ultrasound cardiography (r = 0.79, p < 0.002 in wall thickness, r = 0.84, p < 0.01 in the ratio of septal wall thickness to free wall thickness). Left ventricular shape (ventricular long axis) was closely resemble to that of left ventriculography by contrast medium. In conclusion, 99mTc-Tetrofosmin scintigraphy is useful for the evaluation of myocardial morphology as well as perfusion abnormality. PMID- 8196228 TI - [A problem of quantitative measurement of regional cerebral blood flow using microsphere model and N-isopropyl-p-[123I]iodoamphetamine (IMP): comparison with 133Xe SPECT and sequential dynamic 123I-IMP SPECT]. AB - Regional cerebral blood flow (rCBF) was measured in 13 patients with various cerebral disease by N-isopropyl-p-[123I]iodoamphetamine (IMP) SPECT with the microsphere model (rCBF (CbST)), which was compared with 133Xe inhalation SPECT (rCBFXe). Continuous withdrawal of arterial blood was performed for 5 minutes and SPECT image was obtained from 25 min to 55 min after the tracer injection. The reconstructed counts at 5 min was corrected using entire cerebral counts collected at 5 min, 20 min, and 60 min after the tracer injection. As compared with rCBFXe, rCBF (CbST) was underestimated in high flow areas and overestimated in low flow areas. Regional CBF was also measured using one minute short time SPECT images at 5 min (rCBF (Cb5)), 20 min (rCBF (Cb20)), and 60 min (rCBF (Cb60)) after the injection. Regional CBF tended to be underestimated with time from the tracer injection due to the wash-out from brain tissue to blood. In comparison with rCBF (Cb5), rCBF (CbST) was underestimated in high flow areas and overestimated in low flow areas. This error was considered to be due to the correction of reconstruct counts using entire cerebral counts, because of the kinetic behavior of 123I-IMP was different in each region of the brain. PMID- 8196229 TI - [Basic study for immunoscintigraphy of ovarian cancer using 99mTc labeled F(ab')2 fragments of monoclonal antibody]. AB - Basic study was performed to evaluate the efficacy of immunoscintigraphy of ovarian cancer using 99mTc labeled F(ab')2 fragments of monoclonal antibody OC125 which was reactive with CA125 antigen. Labeling efficiency was 99.9% and colloid formation was not observed. Specific activity was 1.48 GBq (40 mCi)/mg antibody and 99mTc OC125 preparation was stable more than 3 hr after labeling. Percent binding to 10(7) cells of PC-9 cancer cells expressing CA125 antigen was 47.0% in 99mTc OC125 almost the same as that of 125I OC125, Tumor-to-blood ratio for 99mTc OC125 was 5.73 +/- 1.41 at 18 hr after intravenous injection, which was significantly higher than that for 125I OC125. The scintigram showed a good localization in nude mouse bearing PC-9 tumor cells, and the clinical use of 99mTc OC125 is promising for the imaging of ovarian cancer. PMID- 8196230 TI - [Quantification of reversible perfusion abnormality using exercise-stress thallium SPECT before and after coronary revascularization]. AB - Reversible myocardial perfusion abnormality was quantified by bull's eye and unfolded surface mapping methods in exercise thallium SPECT before and after coronary revascularization in 47 patients with angina pectoris, including 34 patients with previous myocardial infarction (PMI) and 13 with effort angina (AP). There was no difference in the incidence or extent of myocardial ischemia between the 2 groups before revascularization. However, the ischemic scores were significantly smaller in PMI group preoperatively than the reductions of the ischemic scores after revascularization. The ischemic scores, preoperatively estimated reversible perfusion abnormality was 32%, 69% and 48% of the improvement of the ischemic score (extent score, severity score, and ischemic area, respectively). Using the 3 ischemic scores, the improvement of perfusion abnormality was well predicted in 70-89% of AP patients but 35-57% of PMI patients. Thus, quantitative analysis in stress thallium SPECT is useful for detecting myocardial ischemia and evaluating the effect of coronary revascularization. However, about a half of myocardial viability was underestimated in one third of PMI patients by the conventional exercise-stress thallium SPECT study. PMID- 8196231 TI - [Quantitative analysis of 123I-metaiodobenzylguanidine myocardial imaging: assessment of its usefulness in patients with congestive heart failure]. AB - To investigate the usefulness of the quantitative analysis of 123I metaiodobenzylguanidine (123I-MIBG) myocardial uptake, we studied 9 normal subjects and 18 patients with congestive heart failure (CHF). Rest myocardial imaging with 123I-MIBG was performed at 20 minutes and 3 hours (delayed image) after 123I-MIBG injection. Rest 201Tl imaging was obtained at 20 minutes after 201Tl injection. In addition to ordinary tomograms, a planar anterior image and a whole body image were supplemented in each imaging. In patients with CHF fractional shortening (%FS) was calculated from echocardiography and left ventricular ejection fraction was obtained from cardiac blood pool imaging with 99mTc at rest. We calculated H/M (heart to mediastinum count ratio) from the anterior planar image and %Uptake (percentage of cardiac uptake of the isotope to total injected dose) from the whole body image. H/M of 123I-MIBG in delayed images separated patients with CHF from normal subjects (2.00 +/- 0.19 vs. 2.56 +/- 0.13, p < 0.01). H/M Ratio (H/M of 123I-MIBG divided by H/M of 201Tl) in delayed image could distinguish these two groups poorly (0.72 +/- 0.12 vs. 0.88 +/- 0.14, p < 0.05). On the other hand, %Uptake of 123I-MIBG was not different between two groups (3.49 +/- 0.60% in CHF, 3.54 +/- 0.34% in normal). But %Uptake of 201Tl was greater in CHF than in normal (5.96 +/- 1.09% vs. 4.70 +/- 0.30%, p < 0.05). When myocardial 123I-MIBG uptake was normalized by myocardial perfusion (%Uptake of 123I-MIBG divided by %Uptake of 201Tl, Uptake Ratio), Uptake Ratio in delayed image could distinguish theses two groups as same as H/M (0.60 +/- 0.05 in CHF, 0.75 +/- 0.05 in normal, p < 0.01). In patients with CHF, H/M of 123I MIBG did not reflect LV function and serum norepinephrine (NE) level. But Uptake Ratio and H/M Ratio in delayed image correlated well with %FS (r = 0.88, r = 0.65), EF (r = 0.80, r = 0.68) and NE level (r = -0.77, r = -0.75). Although the calculation of Uptake Ratio is time consuming and expensive, it was assumed that Uptake Ratio is an useful index to quantitate myocardial 123I-MIBG uptake. PMID- 8196232 TI - [Artifactual defect of inferior myocardium on 123I-metaiodobenzylguanidine myocardial SPECT: characteristic findings and preventive method on phantom study]. AB - Discordance between planar and SPECT image of inferior myocardial defect on 123I metaiodobenzylguanidine myocardial scintigraphy (MIBG) was occasionally observed in the clinical studies. The purpose of this study is to clarify the existence of artifactual myocardial defect on MIBG SPECT image. Phantom study was performed in various kinds of situation using triple gamma camera. Artifactual defect adjacent to the liver was significantly observed in the case of increased liver/heart uptake ratio more than 2:1. Artifactual defect was markedly observed in the 180 degrees than that in the 360 degrees SPECT acquisition. To avoid artifactual defect during SPECT acquisition, liver phantom was moved down to the foot direction (vanishing liver position). In this phantom position, artifactual defect adjacent to the liver was not observed on reconstructed myocardial SPECT image. The vanishing liver position was also applicable to human study. Human body was inclined to right side at an angle of 15 degrees, artifactual defect could be avoided. Further study is needed to analyze the cause of this artifactual defect and to conform the preventive method with vanishing liver position in the routine myocardial SPECT examination. PMID- 8196233 TI - [A quantitative approach to the rCBF response to acetazolamide using 99mTc-HMPAO and graphical analysis]. AB - A simple noninvasive method for a quantitative measurement of brain perfusion is presented using intravenous radionuclide angiography with 99mTc hexamethylpropylene amine oxime (HMPAO). Graphical analysis was employed for the evaluation of the unidirectional influx constant (ku) of the tracer from the blood to the brain and the initial distribution volume (Vn) for the tracer, which is the volume of the exchangeable region plus the plasma space. The ku and Vn values were standardized to provide objective and comparable values, brain perfusion indices (BPI) and corrected Vn (Corr. Vn), between subjects by setting the size ratio of ROI(brain) to ROI(aorta) at 10 and 1, respectively. BPI and Corr. Vn of the whole brain were measured before and 20 min after injection of 1 g acetazolamide. After acetazolamide administration, BPI and Corr. Vn increased in all eight subjects with cerebrovascular diseases and one with a pituitary adenoma, by a mean of x 1.26 and 1.24, respectively. Increase of BPI showed a significant correlation with increase of Corr. Vn. This technique is easy to apply as an adjunct to SPECT and may be helpful in the measurement of brain perfusion changes in the acetazolamide test. PMID- 8196234 TI - [Clinical meaning of 123I-MIBG myocardial SPeCT in patients with dilated cardiomyopathy]. AB - MIBG-myocardial SPECT was performed on patients with dilated cardiomyopathy (DCM) undergoing treatment with beta blocker (Nipradilol). The findings of MIBG myocardial SPECT were compared with the changes in cardiac function obtained by echocardiograms. The patients enrolled in the study were seven males who has been diagnosed as definitely suffering from DCM according to diagnostic guidelines provided by the Ministry of Health and Welfare. The patients were aged 57.5 +/- 10.2 years. Following intravenous administration of 111 MBq (3 mCi) of MIBG, myocardial SPECT was taken 20 minutes, and 4 hours later. The washout rate of the left ventricular wall was higher in the unchanged group (40.7 +/- 1.2%) than in the improved group (30.3 +/- 6.1%). Both the early and delayed images showed higher extent and severity scores for the unchanged group than for the improved group. A correlation of LVEF with the washout rates was demonstrated (r = -0.819, p < 0.05). A correlation was also observed between the variations in LVEF before and after beta blocker therapy with the washout rates (r = -0.969, p < 0.01), MIBG-myocardial SPECT suggested possibility of the evaluation of severity and prognosis in the patients with DCM. PMID- 8196235 TI - [Measurement of serum free thyroxine concentrations using anti-T4 monoclonal antibody]. AB - A new one-step radiolabeled antibody radioassay for measuring free T4 (FT4) in serum (Amerlex-MAB FT4) was evaluated in comparison with an analog tracer RIA of FT4 (Amerlex-M FT4). In this new method, 125I-labeled anti-T4 monoclonal antibody which has cross-reactivity with T3 is used as a tracer. When incubated with serum sample, the tracer binds to FT4 and the remaining tracer binds to a T3 coated particle (Amerlex MAB). The radioactivity bound to Amerlex MAB is measured. Counts of 125I bound to the T3 coated particle were inversely proportional to sample FT4 concentrations. The assay procedure is as follows. Fifty microliter of patient's serum or standard FT4, 500 microliters of Amerlex MAB and tracer is incubated at 37 degrees C for 30 minutes and centrifuged. Then the radioactivity of Amerlex MAB is measured using an autowell gamma counter. The intra-and interassay coefficients of variation were 1.6-2.7% and 2.6-8.0%, respectively. Although Amerlex-M FT4 values were significantly increased by adding human albumin to the serum, Amerlex-MAB FT4 values were not effected by the change of albumin concentrations. In nonthyroidal illness patients, Amerlex-MAB FT4 values were not affected by the concentrations of albumin, TBG and NEFA. The euthyroid central 95% reference range for FT4 determined by Amerlex-MAB FT4 was 0.99 to 1.54 ng/dl. The FT4 levels correlated well with the metabolic status. Although Amerlex-M FT4 values were spuriously increased in patients with anti-T4 autoantibodies, Amerlex-MAB FT4 values were not affected by the autoantibodies. Amerlex-MAB FT4 values of normal pregnant women were slightly lower in the second and third trimesters than in the first trimester. These lower FT4 concentrations in late pregnancy were considered likely not to be artefact by low serum albumin or high serum TBG but to be a physiological event. Amerlex-MAB FT4 values correlated well with FT4 indices and inversely correlated with TSH levels. A significant correlation (n = 401, r = 0.86, p = 0.0001) was observed between Amerlex-MAB FT4 and Amerlex-M FT4 values in various thyroid conditions without antithyroid autoantibodies. In summary, this new assay for FT4 is simple, rapid and reproducible. The measurement is useful for the evaluation of physiological thyroid function and helpful in the management of patients with thyroid diseases. PMID- 8196236 TI - [Clinical nuclear medicine in thyroid diseases]. AB - Both in vivo and in vitro isotopic tests are available for the diagnosis of thyroid diseases. As in vitro tests, serum concentrations of T4, T3, free T4, free T3, TSH, TBG, and thyroglobulin (Tg) are determined by RIA or by IRMA. TSH receptor antibodies are measured by RRA for TSH. In order to differentiate blocking from stimulating antibodies, however, assessment of biological activity of the antibody by another type of method such as TSAb assay is required. Radioassays for anti-Tg and anti-TPO antibodies have recently been developed. The former assay is sensitive enough to make early diagnosis of Hashimoto's thyroiditis. The serum Tg measurement by a newly developed IRMA is applicable even in cases with anti-Tg antibodies. Radiolabeled T4-analogs are most frequently used in the RIA of free T4. A one-step labeled antibody method (Amerlex MAB kit) and a sensitive RIA with use of equilibrium dialysis (Model FT4 kit) have recently been in clinical application in our country. These two assays have an advantage of overcoming two major problems, effects of albumin and anti T4 antibodies, that the analog method has. As in vivo isotopic tests, thyroid scintigraphy using 123I or 99mTc with the combined assessment of the thyroidal uptake rate of each radionuclide and tumor imaging are performed. The thyroid scintigraphy gives functional information, being useful for the differential diagnosis of destructive thyrotoxicosis from Graves' hyperthyroidism. Hypothyroid patients with increased 123I or 99mTc uptake are suspected highly to have dyshormonogenesis or reversible hypothyroidism due to iodine excess.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196237 TI - [Clinical study on reoperation for recurrent pulmonary metastasis]. AB - Ninety seven patients with metastatic lung tumors were treated surgically in our department. Second pulmonary resections were performed in 13 patients. They consists of 9 males and 4 females, their age ranged from 12 to 75 years old (average 54.4 years old). Tumors originate from sarcoma in 5 cases, laryngeal cancer, colorectal cancer, renal cell cancer in 2 cases respectively, oral cavity cancer and transitional cell cancer in 1 case respectively. No second pulmonary resection was performed in patients with metastatic lung tumors originating from lung cancer or breast cancer, because they metastatize not only lung but also general organs. No second pulmonary resection was required in patients with testicular tumor and choriocarcinoma, because chemotherapy take good effect on them. PMID- 8196238 TI - [Effectiveness of fibrin glue in preventing postoperative pulmonary air leakage]. AB - The authors investigated the effectiveness of fibrin glue in preventing pulmonary air leakage after lung surgery. We first examined 29 patients who underwent pulmonary resection without the use of fibrin glue. On the basis of preoperative spirometry data, these patients were divided into normal respiratory function and poor function groups (%VC < 80% and/or FEV1.0% < 70%), and the duration of postoperative pulmonary air leakage in each group was studied. The duration was 2.2 +/- 1.4 days (mean +/- S.D, n = 18) in the normal group and 5.2 +/- 4.3 days (mean +/- S.D, n = 11) in the poor respiratory function group. The latter values were significantly greater than the former (p < 0.05, unpaired t-test). Then we examined seven patients who underwent lung surgery with the use of fibrin glue. We found that in three patients with normal respiratory function, the air leakage disappeared within one day, and in four patients who had poor respiratory function, the air leakage disappeared in three days. In both respiratory function groups, the air leakage seemed to disappear more quickly with the use of fibrin glue. These results suggest that fibrin glue is effective in preventing pulmonary air leakage. PMID- 8196239 TI - [Arterial graft anastomosis in coronary surgery: side by side stitch with parachute technique]. AB - We describe some techniques on arterial graft anastomosis that seem to be useful in coronary artery bypass. The graft is positioned with its cut surface upward, parallel to the left side of the coronary artery from surgeon's view point. The first stitch is placed from the inside of the coronary artery at the mid point of the anastomotic line adjacent to the graft. Then, a single stroke continuous sutures are carried out around the proximal corner of the anastomosis terminating at the one third point of the opposite side of the arteriotomy. After completion of this side by side stitch, the graft is approximated by pulling the suture in such a manner as parachute technique. The rest of the anastomosis can be performed in almost fore hand stroke. The time necessary for anastomosis is ten minutes at most. PMID- 8196241 TI - [Hypothermic cardiopulmonary bypass with circulatory arrest of the lower half of the body and selective perfusion of the upper and lower half of the body for thoracic aortic aneurysm operation]. AB - A 62-year-old man with thoracoabdominal aortic aneurysm of Crawford type IA and a 61-year-old woman with triple descending thoracic aortic aneurysms were operated on under total cardiopulmonary bypass with hypothermic circulatory arrest of the lower half of the body (rectal temperature of 17-19 C) and low flow selective perfusion of the upper and lower half of the body. Low porosity woven Dacron UBE grafts without preclotting were used for the replacement of the aorta. Postoperative courses were uneventful without paraplegia and angiographic examination revealed excellent hemodynamic results. PMID- 8196240 TI - [A case report of successful management of intraoperative aortic dissection during aorta-coronary bypass and aortic valve replacement]. AB - A 70-year-old woman underwent aortic valve replacement and coronary artery bypass surgery with a saphenous vein graft for aortic regurgitation and 99% stenosis in the right coronary artery. During the period of weaning from the cardiopulmonary bypass enlargement of the ascending aorta and bleeding from the suture line were observed. The intraoperative diagnosis of ascending aortic dissection (DeBakey type I) was made with transesophageal and transthoracic echocardiography. Cardiopulmonary bypass was reinstituted and the patients was cooled to 20 degrees C. Under circulatory arrest and continuous retrograde cerebral perfusion through the superior vena cava the intimal tear at the point of infusion cannula was removed and the ascending aorta was reconstructed by direct suture bolstered with Teflon felt strips. Following completion of the repair no further dissection was seen, and the patient was successfully weaned from cardiopulmonary bypass. There were no signs of neurologic complications. Although intraoperative aortic dissection is uncommon, it can be a fatal iatrogenic complication of cardiac operations. Prompt recognition and surgical repair of the injuries are essential to achieve a successful outcome. The combination of transesophageal echocardiography and transthoracic echocardiography permits the immediate diagnosis of aortic dissection. And it is suggested that continuous retrograde cerebral perfusion through the superior vena cava protects the brain for 52 minutes of cerebral circulatory arrest at the lowest nasopharyngeal temperature of 18.7 degrees C. This technique is simple, and required neither special preoperative preparation or special equipment, so that it is suitable especially for intraoperative aortic dissection such as this case. PMID- 8196242 TI - [An experience of suprahyoid release for resection and reconstruction of the lower part of trachea]. AB - An experience of suprahyoid release for resection and reconstruction of the lower part of trachea was reported. 51-year-old woman, complaining of continuous stridor, was diagnosed as tracheal tumor at another hospital and was transferred to our hospital for consecutive examination and surgical treatment. The size of the tumor was about 3 cm in longitudinal diameter and the distance between tracheal carina and lower edge of the tumor was estimated about 2 cm by tomography. At operation, following suprahyoid release in supine position, 6 tracheal rings were resected and reconstructed by end-to-end anastomosis through right posterolateral incision. Patients neck was forced to bend for three weeks and intravenous byperalimentation without oral intake was employed for two weeks to avoid misswallowing and dysphagia postoperatively. Oral intake was started at two weeks after operation and parenteral nutrition was no more necessary at 3 weeks after surgery. Misswallowing and dysphagia were not encountered at all. The tumor was diagnosed as adenoid cystic carcinoma pathologically and residual tumor was demonstrated in submucosal space at the oral margin of the resected specimen as well. She discharged from the hospital uneventfully after postoperative radiotherapy. The recurrence of the tumor has not been observed for 3 years postoperatively. It was confirmed that suprahyoid release is an useful technique and should be ready to introduce in the extensive resection of the trachea because of its little influence on laryngeal function. PMID- 8196243 TI - [A clinical study of so-called rare pulmonary tumors]. AB - Six so-called rare pulmonary tumors, resected at the hospital are reported. Histologically there were pulmonary blastoma, pulmonary adenocarcinoma of fetal lung type, alveolar soft part sarcoma, oncocytic carcinoid tumor, hemangioendothelioma, and leiomyoma in each one case. The represented about 1.5% of all resected lung tumors. The age of these patients ranged from 28 to 67 years old, and all were females. Two patients experienced hemosuputum, but the others have no clinical symptoms. All the patients showed relatively well circumscribed mass shadows on chest X-ray films, but none could have accurate diagnosis by preoperative examinations. One patient with alveolar soft part sarcoma died of brain metastasis 18 months after the resection, however, the other 5 patients remained well from 2 year 7 months to 11 years after the surgery. PMID- 8196244 TI - [Quadricuspid aortic valve: three case reports and review of the literature]. AB - Three patients with grade 3 aortic regurgitation caused by rare congenital quadricuspid valve underwent aortic valve replacement. Patients were two females (51 and 45 years old) and a 51 year-old male. The first case showed 2 equal larger and 2 equal smaller valves. In the latter two cases, 4 equal sized cusps were noted. Fibrous trabeculations bridging the aortic wall and the commissures, giving an appearance of a hammock, were noted in the third case. Small fenestations were also noted in two cusps in this case. These findings may suggest dysplastic feature of the quadricuspid aortic valve. Hypertension seemed to have played an important role in the occurrence of regurgitation in their 4th or 5th decade of life. Their postoperative courses were uneventful. PMID- 8196245 TI - [A case report of Tetralogy of Fallot in the adult with severe congestive heart failure]. AB - We operated on a 47-year-old male for Tetralogy of Fallot with severe right heart dysfunction (RVEF 25%, RVEDP 15 mmHg, massive TR) and right heart failure (ascites and edema). The operation was completed successfully. However, persistent severe arrhythmia occurred in the CCU and assisted circulation was used for 6 days until the patient's condition stabilized. Arrhythmia diminished and hemodynamic status improved gradually. The patient improved sufficiently to be able to eat and read books. Unfortunately, he died of sudden ventricular arrhythmia on 69 POD. It was suspected that the right ventricle in this case had deteriorated beyond the threshold for surviving the radical operation for Tetralogy of Fallot. PMID- 8196246 TI - [Ventricular septal perforation following acute myocardial infarction in an 85 year-old woman]. AB - An 85-year-old woman who experienced sudden severe chest and back pains was admitted to our hospital. On admission a pansystolic murmur was audible and the ECG showed an acute antero-septal myocardial infarction. Right heart catheterization revealed increased oxygen from the right atrium to the right ventricle, leading to the diagnosis of ventricular septal perforation (VSP). Hemodynamics of the patient were stabilized using only a low dosage of dopamine. However the heart weakened progressively, an operation was performed on the 13th day after the onset of the perforation. The post-operative course was uneventful. She is the oldest patient with VSP which has been successfully operated in Japan. PMID- 8196248 TI - [Two cases of coronary artery fistula with coronary artery aneurysm]. AB - Two cases of coronary artery fistula with coronary artery aneurysm were reported. Coronary angiography showed dilated right coronary artery with the formation of aneurysm drained to the right atrium and to the right ventricle respectively. The inflow ostium from the coronary artery to the aneurysm were closed from inside adding aneurysmorraphy. Postoperative clinical courses were uneventful and residual shunts were not detected by angiography. We reported these cases with literature. PMID- 8196247 TI - [A case report of tricuspid replacement for the acquired tricuspid stenosis at the time of reoperation]. AB - A 57-year-old woman, who underwent aortic valve replacement and open mitral commissurotomy nine years ago, was admitted with congestive heart failure due to mitral regurgitation and tricuspid regurgitation, for which we planned mitral valve replacement and tricuspid annuloplasty. Intraoperatively, the orifice of tricuspid valve was stenosed like fish-mouth, which we attempted to make commissurotomy and modified Kay's annuloplasty, but failed to decrease the central regurgitation. A CarboMedics 23 mm prosthesis was implanted in the mitral position and a Capentier-Edwards 29 mm in the tricuspid position. She had recovered from congestive heart failure postoperatively, no regurgitant flow was detected in right ventriculography. PMID- 8196249 TI - [Changes in plasma interleukin 6 in a surgical case of left atrial myxoma]. AB - It was recently described that the cardiac myxoma produced Interleukin-6 (IL-6) as a kind of cytokines, and the constitutional signs in patients with cardiac myxoma were due to the IL-6 production. We measured the values of plasma IL-6 concentration before and after surgical therapy. It was decreased from 7.2 pg/ml to less than 4.0 pg/ml two months after surgical removal of the myxoma. It is recommended that the measurement of IL-6 is useful for screening of cardiac myxoma and postoperative follow-up. PMID- 8196250 TI - [A case of aortic valve-regurgitation associated with Behcet's disease]. AB - The patient was a 37-year-old female with incomplete form of Behcet's disease combined with aortic valve regurgitation. The patients with Behcet's disease often have perivalvular leakage after valve replacement. Special technique is necessary in order to reinforce suture lines and minimize the occurrence of postoperative perivalvular leakage. The aortic valve replacement was accomplished by bolstering mattress sutures with Teflon felt strips and by inserting of sutures from outside the aorta. The latter technique was utilized around the entire circumference of the aortic annulus by opening the right ventricular outflow tract and right atrium and passing sutures from within these structures to enter the aorta. Satisfactory result was obtained with no findings of perivalvular leakage 2 years after operation. The conductive system was not damaged. The operation was performed when the inflammatory signs and findings subsided with adrenal steroids. The steroid therapy has been continued and adjusted by the values of CRP as well as the cutaneous and mucous manifestations. PMID- 8196251 TI - [Treatment of hemopneumothorax under thoracoscopic guidance: a case report]. AB - A 32-year-old man was admitted to our hospital complaining of chest pain and increasing dyspnea. Chest X-ray on admission revealed a collapsed lung and an air fluid line in the left hemithorax. Shock developed following drainage of 1,500 ml hemorrhagic pleural fluid. Following blood transfusion, emergency surgery was carried out. At operation under thoracoscopic guidance, a bleeding artery originating from the apex of the thoracic cavity and a bulla on the upper lobe were noted. The artery was successfully ligated with surgical clip, and the bulla was resected using EndoGIA. This case report indicates that hemopneumothorax can be safely operated on under thoracoscopic guidance after the patient has recovered from shock by adequate blood transfusion. PMID- 8196252 TI - [A case of pulmonary cryptococcosis diagnosed by percutaneous lung biopsy]. AB - A 53-year-old male was admitted with complaint of bloody sputum. The chest X-ray film revealed a solitary round mass with cavity formation in the left upper lung field. A diagnosis of pulmonary cryptococcosis was made by the percutaneous lung biopsy. As his chest X-ray film did not improve even by administration of antimycotic agents for 6 months, he underwent partial resection of left upper lobe. Thus, the percutaneous lung biopsy was a significant procedure for the definitive diagnosis of this case. PMID- 8196253 TI - [A case of traumatic diaphragmatic hernia repaired 40 years after the injury]. AB - A 65-year-old male complaining dyspnea on exertion and epigastric discomfort was diagnosed to have left traumatic diaphragmatic hernia elsewhere and referred to Keio university Hospital for treatment. He had thoracicio-abdominal trauma which was conservatively treated, 40 years ago. Because he was symptomatic and the possibility of future strangulation could not be denied, surgical repair of the hernia was performed. The defect in the diaphragm was too large to be directly sutured and it was repaired with GORE-TEX patch. The gastric fundus partially prolapsed in the paraesophageal region, but the diaphragm was repaired quite satisfactorily otherwise. Pulmonary function and dyspnea on exertion improved. PMID- 8196254 TI - [Comparative study on use of angiotensin-converting enzyme inhibitors and cardiac glycosides in the treatment of cardiac insufficiency]. AB - The efficacy of captopril (capoten) and digoxin was comparatively studied in long term randomized, double blind trials of 22 male patients with postinfarction cardiosclerosis, functional classes I-III and preserved sinus rhythm. The optimal doses of the drugs proved to be small (0.31 and 35 mg/day of digoxin and capoten, respectively). No adverse effects were noted. The mortality rate was 10 and 16.7% with digoxin and captopril, respectively. The drugs equally improved the functional class by 0.51 and 0.45 and VO2 max by 1.5 and 1.7 ml/min. Digoxin had a mild effect on heart rate (-8.4%) and ejection fraction (+5.7%) and deteriorated diastolic relaxation, by slowing down the early peak of transmitral Doppler spectrum by 16.2%. Captopril significantly improved diastolic function by increasing the early peak by 17.2%. No significant changes in left ventricular sizes were recorded. The clinical efficacy of captopril was explained by a significant decrease in angiotension II (70%) and norepinephrine (40%) levels and by associated normalization of baroreflex regulation. Digoxin insignificantly affected the levels of angiotensin II and norepinephrine, but improved the baroreceptor regulation of sympathetic control impaired in chronic heart failure. It is concluded that extracardiac mechanisms play a major role in the action of not only captopril, but digoxin in the treatment of patients with postinfarct cardiosclerosis and chronic heart failure with sinus rhythm. PMID- 8196255 TI - [Effect of capoten on hemostasis of patients with hypertension]. AB - The effects of capoten on hemostasis were studied in 63 patients with Stages I and II hypertensive disease in relation to the hemodynamic type and severity of the disease. Thrombophilia was revealed just at the onset of the disease mainly due to hemostatic endothelial dysfunction which progresses with the hemodynamic development of hypertensive disease. Capoten optimizes hemostatic parameters by affecting endothelial function, which serves an additional mechanism of the antihypertensive effect of the drug. Supplementary techniques affecting the rheological properties should be used in the treatment of hypertensives with moderate-to-serve courses along with resistive hemodynamics. PMID- 8196256 TI - [Correction of postinfarction remodelling of the heart with angiotensin converting enzyme inhibitors]. PMID- 8196257 TI - [Use of captopril and other angiotensin-converting enzyme inhibitors in patients with myocardial infarction]. PMID- 8196258 TI - [Clinical application of cardiomyoplasty]. PMID- 8196259 TI - [Spiroergometric evaluation of functional insufficiency of oxygen transport system in heart surgery]. PMID- 8196260 TI - [Hemodynamic basis of antianginal effect of calcium antagonists in patients with ischemic heart disease after aortocoronary shunting: myocardial reserve potentials and their mechanisms]. PMID- 8196261 TI - [Current approaches to instrumental diagnosis of pulmonary arterial hypertension: qualitative methods of diagnosis (Part I)]. PMID- 8196262 TI - [Leukocytic regulation of hemostasis in the normal and pathologic states]. PMID- 8196263 TI - Dialysis disequilibrium syndrome: current concepts on pathogenesis and prevention. PMID- 8196264 TI - Aluminum alters the compartmentalization of iron in Friend erythroleukemia cells. AB - Aluminum (Al) accumulation in renal failure patients can result in encephalopathy, osteomalacia, and anemia. Since the cellular mechanisms of Al toxicity are not completely understood we used cultured Friend erythroleukemia cells (FEC) as a model system of Al-induced anemia. In this system Al accumulation leads to decreased cell growth and hemoglobin synthesis despite increased iron (Fe) uptake by transferrin (Tf) endocytosis. In FEC we evaluated the effect of Al on the cellular and subcellular accumulation of Fe, ferritin concentration, the uptake of Fe by ferritin, the exit of cellular Fe, and membrane lipid peroxidation. FEC were grown in media with or without the addition of Al-Tf and studies were done at 24, 48, 72, and 96 hours after plating. The highest concentration of intracellular Al was found in mitochondria with lesser amounts in the nucleus, and the least was in cytosol. The rate of Fe uptake was higher in Al-loaded FEC without a proportionally increased rate of exit. This resulted in higher concentrations of Fe in Al-loaded FEC. Subcellular fractionation following the uptake of 59Fe, 125I-Tf in Al-loaded FEC showed increased uptake of 59Fe in the nuclear and mitochondrial compartments with no increase in the cytosol. Al-loaded FEC showed decreased ferritin content and decreased uptake of 59Fe by ferritin. Increased membrane lipid peroxidation occurred in Al-loaded FEC at 96 hours as assessed by cellular malonyldialdehyde accumulation. These results indicate that Al disrupts Fe metabolism in FEC by increasing cellular Fe content with increased compartmentalization of Fe in the mitochondria and nuclei, decreased ferritin content, and decreased uptake of Fe by ferritin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196265 TI - Escape from the antiproliferative effect of transforming growth factor-beta 1 in LLC-PK1 renal epithelial cells. AB - Transforming growth factor-beta 1 (TGF-beta 1) usually inhibits proliferation of epithelial cells. We find that LLC-PK1 renal tubular epithelial cells develop rapid in vitro resistance to the inhibitory effects of TGF-beta 1 and subsequently proliferate in response to TGF-beta 1. This unique response to TGF beta 1 is not observed in another renal tubular epithelial cell line (MDCK cells). The proliferative response to TGF-beta 1 is additive to that produced by other growth factors. The proliferative response to TGF-beta 1 occurs despite an effect of TGF-beta 1 to suppress epidermal growth factor stimulated c-myc mRNA as determined by Northern analyses. These results suggest that LLC-PK1 cells develop rapid resistance to TGF-beta 1 inhibition of proliferation in vitro and that this resistance occurs despite continued suppression of c-myc mRNA. PMID- 8196266 TI - Glomerular prostaglandins modulate vascular reactivity of the downstream efferent arterioles. AB - The balance of vascular resistance in afferent (Af-) and efferent arterioles (Ef Arts) is a crucial factor that determines glomerular hemodynamics. We have recently reported that when Ef-Arts were perfused from the distal end of the Af Art through the glomerulus (orthograde perfusion; OP), both angiotensin II (Ang II) and norepinephrine (NE) induced much weaker constriction than they did when Ef-Arts were perfused from the distal end (retrograde perfusion; RP). This difference was not affected by inhibiting synthesis of nitric oxide. In the present study, we tested the hypothesis that glomerular prostaglandins (PGs) may modulate vascular reactivity of the downstream Ef-Art. In addition, we examined the possible modulatory role of PGs in the Af-Art responses to Ang II or NE. Both Ang II and NE caused dose-dependent constriction of Ef-Arts with either OP or RP; however, the constriction was stronger in RP. At 10(-8) M, Ang II decreased Ef Art diameter by 35 +/- 3.5% in OP (N = 9) compared to 73 +/- 3.9% in RP (N = 5), while 10(-6) M NE decreased the diameter by 25 +/- 3.6% in OP (N = 9) compared to 62 +/- 7.2% in RP (N = 5). Pretreatment with 5 x 10(-5) M indomethacin (Indo) did not alter basal diameter with either method of perfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196267 TI - Polyol pathway mediates high glucose-induced collagen synthesis in proximal tubule. AB - The polyol pathway in diabetes is activated in tissues that are not dependent on insulin for glucose uptake. To examine the role of the polyol pathway in renal extracellular matrix accumulation, we incubated murine proximal tubule cells in either normal or high glucose concentration in the presence or absence of the aldose reductase inhibitor sorbinil. Rising medium glucose from 100 to 450 mg/dl for 72 hours increased cell sorbitol levels sevenfold. Addition of 0.4 mM sorbinil reduced sorbitol content to virtually undetectable levels as measured by gas chromatography. Sorbinil (0.1 to 0.2 mM) also reduced the secretion of collagens types IV and I in the high glucose concentration after 48 to 72 hours but had no appreciable effect in the normal glucose concentration. Concordantly, 0.1 mM sorbinil inhibited the high glucose-induced stimulation of alpha 1(IV) and alpha 2(I) mRNA levels without affecting levels in normal glucose concentration. To study the role of transcriptional activation of collagen genes, we transfected proximal tubule cells with a chloramphenicol acetyltransferase (CAT) reporter gene linked to the promoter and regulatory elements of alpha 1(IV) gene. CAT activity increased several-fold in the cells grown in the high versus normal glucose concentration; this transcriptional activation in culture media containing high glucose concentration was reduced by treatment of the cells with 0.1 mM sorbinil. Thus, high ambient glucose activates the polyol pathway in proximal tubule cells, and may mediate the high glucose-induced stimulation of gene expression for collagens types IV and I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196268 TI - Deferoxamine augments growth and pathogenicity of Rhizopus, while hydroxypyridinone chelators have no effect. AB - Deferoxamine (DFO), when used in dialysis patients, is a well recognized risk factor for the development of mucormycosis caused by Rhizopus. This study compares, both in vivo and in vitro, the effects produced on Rhizopus by DFO and by two chelators of the hydroxypyridinone class, L1 and CP94. Experimental systemic mucormycosis was induced in the guinea pig by an i.v. injection of two different strains of Rhizopus: R. microsporus and R. arrhizus. Concomitant i.p. administration of DFO for four days shortened animal survival (P < 0.05), whereas concomitant administration of either L1 or CP94 did not. In vitro radioiron uptake by R. microsporus was 100-fold higher from the 55ferric complex of DFO than of L1 or CP94. In vitro fungal growth was stimulated sevenfold by the ferric complex of DFO (P < 0.0001) but not significantly by the ferric complex of either L1 or CP94. These results indicate that the ferric complex of DFO but not that of L1 or CP94 specifically stimulates both the iron uptake and the growth of Rhizopus. They suggest that the risk of developing mucormycosis should be minimal with L1 or CP94, as opposed to DFO. PMID- 8196270 TI - Developmental changes in rat renal 11 beta-hydroxysteroid dehydrogenase. AB - 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) transforms endogenous glucocorticoids to their respective "biologically inert" 11-dehydro derivatives. A decrease in enzyme activity allows glucocorticoids to induce mineralocorticoid like renal sodium retention. Since positive sodium balance is required for optimum growth in the newborn, we hypothesized that renal 11 beta-OHSD activity would be low in the postnatal period, a time of active growth. To test this, incubations with corticosterone were carried out using minces or homogenates prepared from kidneys of newborn, 8-day-old, and mature Sprague-Dawley rats. 11 beta-OHSD activity in renal minces, assessed by the percent of corticosterone (10(-8) M) transformed to 11-dehydrocorticosterone (compound A), was significantly lower in the newborn kidney (newborn 45.7 +/- 3.8%, 8 day 70.2 +/- 3.8%, and adult 73.4 +/- 3.1%, P < 0.001 1 vs. 8 day). Parallel studies were conducted using an antibody directed against liver 11 beta-OHSD counter stained with immunofluorescent labeled IgG. Kidneys from mature rats were brightly stained at S2 and S3 segments of proximal tubules. In contrast, staining was barely detectable in kidneys from the newborn and 8-day-old rats. When enzyme kinetics were examined in kidney homogenates (average protein concentration 2.5 mg/ml) in the presence of 200 microM NADP+, the apparent Km for corticosterone in the adult was 4.42 x 10(-6) M with a corresponding Vmax of 1.33 x 10(-9) mol/min/mg protein, while the apparent Km for corticosterone in the newborn was calculated to be 12.8 x 10(-8) M with a Vmax of 2.08 x 10(-11) mol/min/mg protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196269 TI - Tissue-specific modulation of Na, K-ATPase alpha-subunit gene expression in uremic rats. AB - Chronic renal failure in the rat is associated with an impaired extrarenal potassium handling, whereas a renal adaptive mechanism of the remaining nephrons has been described. To understand the molecular basis of potassium homeostasis during renal failure we investigated the in vitro pump activity and the catalytic mRNA transcription in three different tissues: skeletal muscle, isolated adipocytes and kidney. The activity of the sodium pump, as measured by ouabain sensitive 86Rb/K uptake in isolated adipocytes and skeletal muscle fibers, revealed a significant reduction of the pump activity in uremic rats. The reduction of the Na, K-ATPase activity in adipose tissue was associated with a similar decrement of both catalytic subunits (alpha 1 and alpha 2), whereas in the skeletal muscle tissue was only related to a decrease in the activity of the alpha 1 isoform. The expression of rat Na, K-ATPase catalytic isoforms mRNAs in kidney, muscle and adipose tissue from control and chronic renal failure rats was investigated at the molecular level with cDNA probes specific for the catalytic isoforms (alpha 1 and alpha 2). Northern blot analysis revealed that the respective catalytic mRNAs of uremic rats are regulated in a tissue-specific manner that are in agreement with the sodium-potassium pump activity. Muscle and adipose tissue showed a decrement in the levels of expression for the alpha 1 isoform mRNA. In contrast to these tissues, an increment in alpha 1 mRNA expression was observed in the kidney of rats with chronic renal failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196271 TI - Experimental nephrotoxicity, hepatotoxicity and pharmacokinetics of cyclosporin G versus cyclosporin A. AB - Cyclosporin G (CsG) is an analogue of cyclosporin A (CsA) with strong immunosuppressive activity. We compared these two drugs in a rat model in which salt depletion promotes irreversible renal interstitial fibrosis with renal dysfunction in animals given CsA for three weeks. When both drugs were given in the same dosage on a weight basis (15 mg/kg/day, subcutaneously), CsA blood levels were higher than CsG (3305 vs. 1824 ng/ml, P < 0.001). This could be explained by a higher CsG clearance (6.4 vs. 4.3 ml/min/kg in CsA, P < 0.0001) resulting in smaller CsG area under the curve. There was also lower renal and hepatic CsG tissue concentrations. CsA induced a dramatic decrease in GFR, 0.14 in CsA versus 0.67 ml/min/100 g in control, P < 0.001, and increased urinary excretion of N-acetyl beta-D-glucosaminidase (NAG), 21 in CsA versus 13 IU/gCr in control rats, P < 0.001. CsG-treated and control rats had similar GFR and urinary NAG. When CsA dosage was decreased to 7.5 mg/kg blood levels were similar to those found with CsG 15 mg/kg. CsA at this dose caused a reduced GFR (0.29 ml/min/100 g) and an increased urinary NAG (20 IU/gCr) (P < 0.01 vs. control for both). Both dosages of CsA induced considerable cortical and medullary injury (interstitial fibrosis and tubular atrophy), more severe than the histological damage found in CsG-treated rats. Neither drug promoted significant changes in liver function or histology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196272 TI - Effects of neurohypophyseal antagonists in postnephrectomy natriuresis in male rats. AB - Acute unilateral nephrectomy (AUN) in anesthetized male Lewis x DA rats induced rapid and consistent increases in electrolyte and fluid excretion by the remaining kidney during the first hours. Continuous infusion of a vasopressin (AVP) V1-receptor antagonist d(CH2)5Tyr(Me)AVP (V1-ant) reduced renal electrolyte and fluid excretion before and after AUN to a similar extent, whereas an oxytocin (OT)-receptor antagonist [Mpa1,D-Tyr(Et)2,Thr4,Orn8]-OT (CAP) at the same dose selectively attenuated the increase in sodium excretion after AUN. The plasma concentration of OT rose significantly after AUN (9.16 +/- 1.4 to 21.45 +/- 5.07 pg.ml-1). A similar OT level obtained by infusion of OT mimicked the renal responses to AUN without elevating blood pressure; however, only CAP but not V1 ant efficiently reversed OT-induced natriuresis. Also, the infusion of CAP at the same dose produced no effects on the rise of blood pressure caused by AVP while the infusion of the V1-ant prevented such a rise. Thus, CAP reduced the natriuresis after AUN by interfering with OT- and not V1-receptors. In conclusion, evidence is presented, for the first time, concerning the major role of OT receptors in the acute readjustment of the renal sodium excretion after AUN, and a synergistic role for AVP in terms of the general magnitude of renal excretion. PMID- 8196273 TI - Characterization and distribution of interstitial cell types in the renal cortex of rats. AB - A precise classification of the cellular components of the cortical peritubular interstitium is missing in spite of its physiological and pathophysiological importance. By combining electronmicroscopy and immunohistochemistry we attempted to better identify and localize the different interstitial cell types in rat kidney, with special attention to the cortex. Antibodies against common leukocyte antigen (OX1), a macrophage antigen (ED 2), MHC class II antigen (OX6) and ecto 5'-nucleotidase were applied to cryostat sections. The two latter antibodies were used additionally in electron microscopy. Four groups of cell types were identified that displayed distinct antigenic patterns, distributions and morphological features. They were identified as fibroblasts, dendritic cells, macrophages and lymphocytes. Fibroblasts and dendritic cells constituted the most abundant cell types in the cortex and outer medulla, and they were rather uniformly distributed in these zones throughout the peritubular interstitium, where macrophages were very scarce. The latter were abundant in the connective tissue of large vessels and of the pelvic wall. The incidence of lymphocytes was generally low. These data may be helpful on the one hand for the further phenotypic characterization of renal interstitial cells and on the other hand for the evaluation of the roles of those cells in pathological processes. PMID- 8196274 TI - COL4A5 gene deletion and production of post-transplant anti-alpha 3(IV) collagen alloantibodies in Alport syndrome. AB - Mutations in the COL4A5 gene encoding the alpha 5(IV) chain of type IV collagen have been implicated as the primary defect in X-linked Alport syndrome. Several kinds of mutations have been reported so far, spanning point mutations to complete gene deletions. About 5% of Alport patients, who undergo renal transplantation, develop anti-glomerular basement membrane (GBM) nephritis, causing loss of allograft function. In one such patient, COL4A5 gene deletion was recently identified. In the present study, the GBM constituent, targeted by the anti-GBM alloantibodies from the patient who had complete COL4A5 gene deletion was identified. Its identity was determined on the basis of circulating antibody binding to various GBM constituents, domains of bovine type IV collagen and recombinant NC1 domain of human type IV collagen. These results establish, for the first time, the absence of the alpha 5(IV) chain in Alport GBM and, in the same patient, the production of an alloantibody that is targeted to a different chain of type IV collagen, the alpha 3(IV) chain. These findings provide further support for the hypothesis that: (1) anti-alpha 3(IV) collagen alloantibodies mediate the allograft glomerulonephritis; and (2) COL4A5 gene mutations cause defective assembly of the alpha 3(IV) collagen alloantibodies mediate the allograft glomerulonephritis; and (2) COL4A5 gene mutations cause defective assembly of the alpha 3(IV) chain in Alport GBM, as reflected by the production of anti-alpha 3(IV) alloantibodies. PMID- 8196275 TI - Metabolic support of Na+ transport by the rabbit CCD: analysis of the use of equivalent current. AB - The role of metabolism in the support of ion transport by the cortical collecting duct (CCD) is being increasingly recognized as a complex process involving energy supply to the Na+/K+ pump and maintenance of cellular conductive pathways. In order to assess both of these processes, we measured the metabolic support of Na+ transport using transepithelial electrical measurements and, in some cases, simultaneous determination of lumen-to-bath Na+ flux. Analysis of the calculated equivalent current (Ieq), the product of the transepithelial voltage and conductance, showed a predicted (and a measured) discrepancy between this value and the magnitude of active Na+ transport. Under conditions of this study, the change in Ieq in a single tubule was a reasonable index of the change in Na+ transport. The majority of the support of Na+ transport appears to come from oxidative metabolism. Glucose supports transport better than the other substrates tested, but lactate, pyruvate, and some acids provide near maximal support. We found some conditions where large changes in Na+ transport occurred without significant changes in conductance. Conductance could also be altered without producing major changes in transport. These results demonstrate complex and possibly independent influences of metabolism in the regulation of Na+ transport and cell conductive pathways. PMID- 8196276 TI - Tubular lipidosis: epiphenomenon or pathogenetic lesion in human renal disease? AB - Tubular lipidosis is a commonly observed histological lesion in proteinuric renal diseases. We have studied the interaction between native and modified human lipoproteins and human renal proximal tubular cells to investigate whether lipoproteins could be injurious to tubular cells in culture. Human renal proximal tubular cells were cultured and characterized by established methods. Preliminary studies showed that these cells could take up and degrade normal human lipoproteins by high affinity (HDL) and low affinity (LDL) pathways. In subconfluent culture, native lipoproteins, that is, LDL, HDL2 and HDL3, had markedly different effects on cell growth as measured by 3H-thymidine uptake and total cell protein as compared to modified lipoproteins such as minimally modified and oxidized LDL. In addition, we found that renal tubular cells could oxidized native LDL in the presence of copper largely by a superoxide-mediated mechanism. Finally, cellular accumulation of lipid was demonstrated in vitro by incubating cultured cells with varying lipoprotein concentrations for up to 48 hours. Notably, cell detachment was observed only with high concentrations of modified LDL especially with minimally modified LDL. We speculate that uptake and oxidation of filtered LDL by tubular cells may lead to tubular injury in nephrotic states. PMID- 8196277 TI - Activation of autoreactive T-lymphocytes by cultured syngeneic glomerular mesangial cells. AB - The capacity of intrinsic, glomerular mesangial cells (MC) to cause an autoreactive response of syngeneic lymphocytes in vitro are presented. Initial experiments demonstrated the MHC class II dependent capacity of MC to present exogenous antigen to sensitized lymph node lymphocytes (LN) and to activate naive, allogeneic LN in the absence of a nominal antigen. However, the most striking finding of the present investigation was that mouse MC (C57BL/6 or DBA/2) augmented a significant activation of naive, syngeneic lymphocytes. The extent of the proliferative lymphocyte response was comparable to that observed after stimulation with allogeneic MC. Moreover, during syngeneic coculture substantial amounts of interferon bioactivity were generated. Equipotent concentrations of rm IFN-gamma were sufficient to induce class II MHC expression of mouse MC. In control experiments the macrophage cell line, IC-21 (C57BL/6), or freshly prepared DBA/2 mouse peritoneal macrophages did not elicit a syngeneic LN response. Using MC, which had not been pretreated, the MC-specific LN stimulation occurred after prolonged periods of coculture. The stimulation index (S.I.) was 9.77 after 144 hours compared with LN controls (S.I. = 1). However, a 48 hour pretreatment of MC with either rm IFN-gamma alone or in combination with rh TNF alpha and/or the continuous presence of rm IL-1 alpha during coculture periods from 72 to 144 hours substantially enhanced the proliferative LN response. Analysis of non-adherent LN by flow cytometry (FACS) after 96 or 120 hours coculture with MC revealed an increased ratio of Thy1.2+ to B220+ cells with a predominant rise of L3T4+ T-helper cells compared to Lyt2+ cytotoxic T-cells. Furthermore, immune fluorescence microscopy showed that a fraction of Thy1.2+ lymphoblasts adhered to MC. FACS analysis of these adherent LN after detachment demonstrated that in comparison to cocultures with untreated MC, cocultures of LN with IFN-gamma/TNF-alpha pre-treated MC resulted in a 24.4% increase of Thy1.2+ cells, with 89% of these being L3T4+ T-helper lymphocytes. In conclusion, autoreactivity of preferentially T-helper cells to cocultured glomerular MC was shown, which may represent a useful model of T-lymphocyte dependent glomerulonephritis. PMID- 8196278 TI - Glomerular thrombosis in pregnancy: role of the L-arginine-nitric oxide pathway. AB - E. coli endotoxin (LPS) and certain cytokines induce synthesis of nitric oxide (NO) from L-arginine, but also promote endothelial injury and intravascular coagulation. NO has vasodilator and antithrombogenic properties. We investigated the relationship between the L-arginine-NO pathway and the susceptibility to LPS induced glomerular thrombosis in pregnancy. Pregnant rats were given either 0.15 or 0.75 mg/kg/body wt of LPS intraperitoneally. In rats given 0.15 mg/kg/body wt of LPS urinary NO2-/NO3- (end products of NO) increased 200% (P < 0.05), plasma L arginine did not change, and glomerular thrombosis was minimal. Pregnant rats given 0.75 mg/kg/body wt of LPS developed glomerular thrombosis in 75% of glomeruli (P < 0.05). In these rats plasma L-arginine fell 98%, from 53 +/- 4 to 1.4 +/- 0.9 mmol/liter (P < 0.05) but the urinary NO2-/NO3- did not increase. Oral administration of L-arginine but not D-arginine increased urinary NO2-/NO3- by 250% and averted glomerular thrombosis in these rats (P < 0.05). Virgin rats given 0.75 mg/kg/body wt of LPS did not contract glomerular thrombosis. In these rats plasma L-arginine decreased only 40% while urinary NO2-/-NO3- concomitantly increased over 200% (P < 0.05). Plasma endothelin-1 increased only in rats exhibiting glomerular thrombosis. Thus, limited maternal reserve capability for NO synthesis may underlie, at least in part, the susceptibility for glomerular thrombosis in pregnancy. PMID- 8196279 TI - Low plasma and renal tissue levels of L-arginine in rats with obstructive nephropathy. AB - Rats with bilateral ureteral obstruction (BUO) of 24 hours duration had significantly lower plasma levels of L-arginine than at baseline (P < 0.0001), but no significant changes occurred in sham-operated rats (SOR). In contrast, rats with bilateral nephrectomy had greater plasma levels of L-arginine four hours (P < 0.03) and 24 hours (not significant) after nephrectomy than at baseline. Total body irradiation prior to obstruction prevented the decrease in plasma levels of L-arginine in rats with BUO but had no effect on these values in SOR. Renal tissue levels of L-arginine were 20% lower in rats with BUO than in SOR. Total body irradiation prior to BUO resulted in greater renal tissue levels of L-arginine than occurred in nonirradiated rats with BUO (P < 0.002). Total body irradiation did not effect renal tissue levels of L-arginine in SOR. Excretion of reactive nitrogen intermediates in urine (URNI), indicative of L arginine metabolism through the nitric oxide pathway, was lower in rats with BUO than in SOR (P < 0.001). Proximal tubules from rats with BUO synthesized less L arginine than those from SOR (P < 0.02). The results indicate that: (1) decreased levels of L-arginine in plasma and renal tissue of rats with BUO correlate with leukocyte infiltration of the kidney, and (2) decreased synthesis of L-arginine occurs in proximal tubules of rats with BUO when compared to tubules from SOR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196280 TI - Measurement of intracellular generation of hydrogen peroxide by rat glomeruli in vitro. PMID- 8196281 TI - Acute and chronic effects of thromboxane A2 inhibition on the renal hemodynamics in streptozotocin-induced diabetic rats. AB - We examined acute and chronic effects of thromboxane (TX) A2 inhibition on the renal hemodynamics at early and late stage of untreated streptozotocin (STZ) induced diabetic rats. Two weeks and 28 weeks after the induction of diabetes, renal blood flow (RBF) under anesthesia was measured with an electromagnetic flowmeter before and after TXA2 inhibition. In two-week-old diabetic rats, a specific TXA2 synthetase inhibitor, OKY-046, or a specific TXA2 receptor antagonist, Sulotroban, increased renal vascular resistance (RVR) and ameliorated the hyperperfusion. The renal vasoconstrictive effect of OKY-046 was blunted by an angiotensin converting enzyme (ACE) inhibitor, MK422, or an angiotensin II receptor antagonist, Saralasin. On the contrary, OKY-046 ameliorated the renal hypoperfusion by decreasing RVR in 28-week-old diabetic rats. Chronic oral administration of OKY-046 ameliorated not only the renal hyperperfusion but increased urinary albumin excretion (UAE) at two weeks, but also the renal hypoperfusion, filtration fraction and UAE at 24 weeks. It is suggested that TXA2 might, at least in part, play important roles in the hyperperfusion by modulating activity of the renin-angiotensin system at an early stage of untreated diabetic rats and in the hypoperfusion at the late stage of untreated diabetic rats, and that TXA2 is also involved in the increase of UAE. These results support roles for TXA2 in the progression of renal injury in STZ-induced diabetic rats. PMID- 8196282 TI - Cl- channels in basolateral renal medullary vesicles. VIII. Partial purification and functional reconstitution of basolateral mTAL Cl- channels. AB - Cl- channels fused from basolateral mTAL membranes into planar bilayers have distinctive functional characteristics which, when taken together, are unique among Cl- channels. The properties of these 50 to 60 pS channels can account for the characteristics of basolateral Cl- conductances in microperfused mTAL segments and thus may mediate net basolateral Cl- absorption in the intact mTAL. In the present studies, we solubilized basolateral membranes from rabbit mTAL. Since basolateral mTAL Cl- channels contain arginine- and lysine-rich domains, we exposed these solubilized membranes to sequential cation- and anion-exchange chromatography. The bound and unbound eluates from cation- and anion-exchange chromatography were reconstituted into proteoliposomes which, when fused into bilayers, yielded Cl- channels whose properties were virtually identical to those described above for native basolateral mTAL channels fused into bilayers. As judged by valinomycin-sensitive conductive 36Cl- uptake, proteoliposomes reconstituted from the unbound eluates after anion-exchange chromatography were enriched at least 30-fold in Cl- channel activity and had about 30% of the total Cl- channel activity solubilized in native vesicles. PMID- 8196283 TI - Cell Ca2+ response to luminal vasopressin in cortical collecting tubule principal cells. AB - Although vasopressin V1 receptors have been shown to exist in both luminal and basolateral membranes of rabbit cortical collecting duct (CCD), exact cell types having V1 receptors remain unestablished. To identify the distribution of V1 receptor by cytoplasmic Ca2+ response, we utilized the confocal imaging system in the microperfused rabbit CCD. Basolateral application of arginine vasopressin (AVP) increased [Ca2+]i mainly in one group of cells which were not stained by fluorescein-isothiocyanate-conjugated peanut agglutinin. Luminal application of AVP increased [Ca2+]i in the same cells which responded to basolateral AVP. These findings provide evidence that V1 receptors, as defined by the [Ca2+]i response, exist in both luminal and basolateral membranes of the rabbit principal cell. PMID- 8196284 TI - Clusterin depletion enhances immune glomerular injury in the isolated perfused kidney. AB - Clusterin is a normal plasma protein, shown to be an inhibitor of reactive complement hemolysis and a component of the fluid phase SC5b-9 terminal complement complexes. It is a component of glomerular immune deposits in human and experimental glomerulonephritis. Using the complement-dependent isolated perfused rat kidney model of autologous phase passive Heymann nephritis, we have studied the effect of clusterin depletion of perfused plasma on the development of glomerular injury. Kidneys with planted glomerular sheep anti-rat Fx1A antibody were perfused with human plasma either depleted of clusterin to < or = 30%, or control plasma depleted of plasma fibronectin. Glomerular injury was then initiated by the addition of guinea pig anti-sheep immunoglobulins to the perfusate. Kidneys perfused with clusterin depleted plasma developed significantly greater proteinuria at all time points when compared to control kidneys. Glomerular antibody binding and C3 deposition were similar in the two groups, but terminal complement components were deposited in larger amounts in the clusterin depleted group. These data support a possible role for clusterin in vivo in the protection of complement-induced glomerular injury. PMID- 8196285 TI - Expression of clusterin in human renal diseases. AB - Clusterin, a glycoprotein with potent cohesive properties, is induced in a wide variety of acute and chronic experimental renal diseases. The purpose of this study was to examine clusterin expression in human renal diseases. Clusterin immunostaining was examined in nephrectomy specimens from patients with autosomal dominant polycystic kidney disease (N = 5), autosomal-recessive polycystic kidney disease (N = 3), multilocular cyst of the kidney (N = 2), renal hypoplasia/dysplasia (N = 7), Wilms' tumor (nephroblastoma) (N = 6), renal cell carcinoma (N = 9), and acute and/or chronic renal transplant rejection (N = 15). No clusterin staining was detected in normal renal tissue distant from renal cell carcinomas. Increased expression of clusterin was found in epithelial cells lining cysts in all of the cystic disorders studied. Clusterin expression was found in some immature tubules in hypoplastic/dysplastic kidneys and in tubules of rejected renal allografts, but was not a prominent finding in renal neoplasms, although some renal cell carcinomas expressed clusterin in a focal manner. Common features of clusterin induction included exclusively epithelial production of clusterin in cysts, immature nephrons, and injured tubules, heterogeneity of clusterin expression, with only some tubules and/or cysts in a given area staining for clusterin, and uniform clusterin staining of epithelial cells in a given tubule or cyst in most cases. Based on its cohesive properties, we speculate clusterin functions to maintain cell-cell and cell-substratum interactions which become perturbed in the setting of renal injury and cystic diseases. PMID- 8196286 TI - Expression of J chain mRNA in duodenal IgA plasma cells in IgA nephropathy. AB - Glomerular IgA in IgA nephropathy (IgAN) is at least in part polymeric, and is thought to derive from the mucosal IgA system in view of the association between mucosal infection and haematuria in this condition. To investigate this hypothesis, an in situ hybridization (ISH) technique was developed for the detection of J chain mRNA, the expression of which has been correlated with the secretion of high level polymeric immunoglobulin (pIg). Endoscopic duodenal biopsies from ten patients and matched controls were examined by: (i) two color immunofluorescence (IF); (ii) ISH; and (iii) combined ISH and IF, to permit simultaneous identification of plasma cell type. IF revealed a reduction in the percentage of IgA plasma cells (P < 0.02) and increased absolute numbers of IgG cells (P < 0.02) in patient biopsies. ISH demonstrated fewer J chain mRNA expressing plasma cells (P < 0.005) with lower signal intensity (P < 0.002) in patients' biopsies compared with controls. Combined ISH and IF confirmed a reduction in J chain mRNA-positive IgA plasma cells in the patient biopsies (P < 0.02). The reduction in J chain mRNA expression in duodenal IgA plasma cells in IgAN argues against the gastrointestinal lamina propria as the source of glomerular pIgA. PMID- 8196287 TI - Antiplatelet therapy and development of hypertension induced by recombinant human erythropoietin in uremic patients. AB - The pathogenesis of hypertension induced by recombinant human erythropoietin (rHuEPO) remains a subject of intense interest. The observation that patients treated with antiplatelet drugs never developed hypertension following rHuEPO therapy prompted us to study retrospectively the incidence and risk factors associated with the development of hypertension in 91 patients on renal replacement therapy who had commenced rHuEPO therapy in the last three years. Logistic regression analysis was used to determine the risk factors associated with the development or aggravation of hypertension during the first six months on rHuEPO therapy. The predictors were: age, gender, number of months on dialysis, antecedent of hypertension, use of antiplatelet drugs, and those parameters related with dose, route and magnitude of the hematological response to rHuEPO. Of the 91 patients studied, 34 developed hypertension (37%). Of the 34 patients who were on antiplatelet treatment, 2 (5.8%) developed hypertension, whereas among 57 who did not receive antiplatelet drugs, 32 (56%) developed it. By multiple logistic regression analysis, the best predictive variables over the development of hypertension were: age (odds ratio: 0.959, P = 0.02), antecedent of hypertension (odds ratio: 6.52, P = 0.002), and use of antiplatelet therapy (odds ratio: 0.030, P < 0.0001). The rest of the studied variables failed to explain the development of hypertension. Antiplatelet therapy may prevent the development of hypertension in patients treated with rHuEPO. Since the antiplatelet drugs used in this study did not have a significant hemodynamic effect, we infer that changes in platelet aggregability induced by rHuEPO may be involved in the pathogenesis of hypertension induced by this hormone. PMID- 8196288 TI - Short-term effects of low protein-normal sodium diet on renal function in chronic renal failure. AB - To investigate the short-term renal effects of protein restriction and unchanged salt intake in chronic renal failure (CRF), patients with moderate CRF (creatinine clearance 41 +/- 5 ml/min) and healthy controls (CON) ate a normal protein diet (NPD) for four weeks, and thereafter a low protein diet (LPD, 0.4 g/kg body wt/day) for three weeks. The two diets were isocaloric and with a salt intake of 10 to 13 g/day. No differences in body weight, serum proteins and plasma sodium were recorded throughout the study. During LPD, inulin and PAH clearances in CON demonstrated a progressive 25% decline of basal GFR and RPF; on the contrary, in CRF, basal renal function did not change in presence of a significant reduction of proteinuria. In CON patients after protein restriction, fractional free-water generation (CH2O/CIn) and fractional urinary excretion of sodium (FENa) measured under maximal water diuresis increased progressively, both being doubled at the end of LPD, while in CRF, CH2O/CIn did not change and FENa values remained unmodified and much higher (above 4%) than in CON after both diets. The renal response to an acute oral protein load (OPL) and i.v. low-doses of dopamine (D) was measured at the end of each period; in the two groups, GFR and RPF significantly increased following OPL + D after both diets. In CRF, however, the vasodilatory response was blunted overall being reduced after both LPD and NPD, and, unlike CON, it did not increase after LPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196289 TI - Is the antiproteinuric effect of ACE inhibition mediated by interference in the renin-angiotensin system? AB - Angiotensin converting enzyme (ACE) inhibition causes specific renal effects, such as a rise in effective renal plasma flow, a fall in filtration fraction and a lowering of proteinuria. The mechanism of these renal effects is still debated. Recent animal studies suggest that non-angiotensin (Ang) II related actions of ACE inhibition, such as bradykinin accumulation, may have a role. We therefore investigated the effects of specific intervention in the renin-angiotensin system with the Ang II receptor antagonist losartan, and compared these effects to those obtained with ACE inhibition, as this comparison might resolve the question whether or not the effects of ACE inhibition are Ang II related. The effects of losartan and enalapril were studied in eleven patients with non-diabetic proteinuria and hypertension. The protocol consisted of seven periods, each lasting one month, in which patients received once daily placebo, 50 mg losartan, 100 mg losartan, placebo, 10 mg enalapril, 20 mg enalapril, and placebo, respectively. At the end of each study period proteinuria, blood pressure, and renal function were determined. On both doses of losartan and enalapril proteinuria and blood pressure fell, whereas ERPF increased and GFR remained stable. The fall in urinary protein excretion was similar for both drugs: 46.3% (28.3% to 63.1%) on 100 mg losartan versus 51.6% (37.0% to 69.2%) on 20 mg enalapril (expressed as Wilcoxon-based estimated median with 95% CI).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196290 TI - Fc alpha R expression on polymorphonuclear leukocyte and superoxide generation in IgA nephropathy. AB - Superoxide (O2-) production and Fc alpha R antigen expression of circulating polymorphonuclear leukocytes (PMNL) isolated from patients with IgA nephropathy (IgAN) and non-IgA mesangial proliferative glomerulonephritis (PGN) and healthy volunteers were investigated to establish their biological importance in the immunopathogenesis of mesangial proliferative glomerulonephritis. PMNL from both patient groups showed increased O2- production when stimulated with N-formyl methionyl leucyl phenylalanine (FMLP) and phorbol myristate acetate (PMA). The increased O2- generation demonstrated a positive correlation with the degree of proteinuria. Aggregated IgA caused enhanced O2- production only in patients with IgAN who also showed a significant correlation with proteinuria. Increased expression of Fc alpha R on circulating PMNL was observed in IgAN patients as determined by flow cytometric analysis. The amount of Fc alpha R on PMNL was positively correlated with O2- generation triggered with IgA aggregates. These results suggest that: 1. Circulating PMNL may potentially be participating in the pathogenesis of glomerular injury in mesangial proliferative glomerulonephritis, and 2. IgA aggregates/immune complexes may contribute to the immunopathogenesis of IgAN through augmenting the Fc alpha receptor-mediated generation of superoxide anion. PMID- 8196291 TI - Enhanced LDL oxidation in uremic patients: an additional mechanism for accelerated atherosclerosis? AB - Since oxidized low-density lipoprotein (LDL) is more atherogenic than native LDL, LDL oxidation was investigated in uremic patients who often develop accelerated atherogenesis. Three groups of uremic patients were studied (10 on predialysis conservative therapy, 11 on repetitive hemodialysis, 13 on peritoneal dialysis) and compared with seventy matched controls. LDL oxidation was evaluated in all patients as: (i) the susceptibility to in vitro oxidation (by measuring the resistance to Cu(++)-induced formation of conjugated dienes), (ii) vitamin E concentration in LDL, and (iii) presence of plasma anti-oxidized LDL antibodies, expressed as the ratio anti-oxLDL/anti-nativeLDL antibodies. The lipid profile was studied in all patients. Vitamin E concentration did not differ between the various groups, although LDL from uremic patients appeared more susceptible to in vitro and in vivo oxidation (as demonstrated by an earlier generation of conjugated dienes and by the presence of an higher antibody ratio) compared to control subjects. Subclass analysis of the different patients revealed that peritoneal dialysis treatment ameliorated the oxidation markers. However, a prolonged dialytic treatment caused a decrease in vitamin E concentration in LDL and increased their susceptibility to oxidation. PMID- 8196292 TI - Magnetic resonance, a new method for measuring blood flow in hemodialysis fistulae. AB - Blood flow through arteriovenous fistulae in patients undergoing hemodialysis needs to be within a certain range for optimal management. Magnetic resonance (MR) velocity mapping is a new modality that allows the noninvasive measurement of blood flow volume. This technique was applied in 13 patients with either a Brescia-Cimino shunt (N = 6) or a Polytetrafluoroethylene graft (Goretex, N = 7). Fistula flow volume measured by MR velocity mapping was 1386 +/- 411 ml/min (mean +/- SD, range 644 to 1921 ml/min). Interstudy reproducibility of MR velocity mapping was good (r = 0.94). Interstudy reproducibility of MR velocity mapping was good (r = 0.94). MR velocity mapping derived flow volumes showed good correlation with values obtained with an indicator dilution technique using Indocyanine Green (ICG) which was performed simultaneously in eight patients (r = 0.86). We conclude that MR velocity mapping is an accurate noninvasive method to quantify flow volume through arteriovenous fistulae in patients requiring hemodialysis. PMID- 8196293 TI - Plasma levels of IL-1 beta, TNF alpha and their specific inhibitors in undialyzed chronic renal failure, CAPD and hemodialysis patients. AB - The presence of naturally occurring inhibitors of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in a variety of diseases has been demonstrated. The IL-1 receptor antagonist (IL-1Ra) binds to IL-1 receptors and blocks the activity of IL-1, and a soluble form of the p55 TNF receptor (TNFsRp55) binds and neutralizes TNF. In the present study, plasma levels of IL-1 beta, IL-1Ra, TNF alpha and TNFsRp55 were measured in 29 undialyzed patients with chronic renal failure (CRF), 13 patients on continuous ambulatory peritoneal dialysis (CAPD), 42 patients on chronic hemodialysis (HD) and in 15 healthy controls. Of the 29 patients with CRF, 13 had end-stage renal disease (ESRD, estimated GFR < 10 ml/min). Among health controls, plasma levels of IL-1 beta, IL-1Ra and TNF alpha were at or below the limit of detection of the assay. In undialyzed patients with ESRD, or in patients on CAPD or HD, plasma levels of IL-1 beta were 428 +/- 134 pg/ml, 378 +/- 83 and 352 +/- 43 pg/ml, respectively. Although plasma levels of IL-1 beta in each group of patients were higher than those in healthy controls (< 160 pg/ml), these differences were not statistically significant. In contrast, plasma levels of IL-1Ra in undialyzed patients with ESRD (629 +/- 125 pg/ml, P = 0.03), CAPD (902 +/- 164 pg/ml, P < 0.0001) and HD patients (642 +/- 73 pg/ml, P = 0.004) were significantly higher than those in healthy controls (103 +/- 15).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196294 TI - Effects of erythropoietin therapy on the lipid profile in end-stage renal failure. AB - To evaluate the effects of erythropoietin (EPO) therapy on the lipid profile in end-stage renal failure, we undertook a prospective study in patients on both hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). One hundred and twelve patients (81 HD, 31 CAPD) were enrolled into the study. Lipid parameters [that is, total cholesterol and the LDL and HDL subfractions, triglycerides, lipoprotein (a), apoproteins A and B], full blood count, iron studies, B12, folate, blood urea, aluminium and serum parathyroid hormone were measured prior to commencement of EPO therapy. Ninety-five patients were reassessed 5.2 +/- 0.3 (mean +/- SEM) months later and 53 patients underwent a further assessment 13.1 +/- 0.6 months after the commencement of EPO, giving an overall follow-up of 10.0 +/- 0.6 months in 95 patients. As expected, EPO treatment was associated with an increase in hemoglobin (7.7 +/- 0.1 vs. 9.9 +/- 0.2 g/dl; P < 0.001) and a decrease in ferritin (687 +/- 99 vs. 399 +/- 69 micrograms/liter; P < 0.01). A significant fall in total cholesterol occurred (5.8 +/- 0.1 vs. 5.4 +/- 0.2 mmol/liter; P < 0.05) in association with a fall in apoprotein B (1.15 +/- 0.04 vs. 1.04 +/- 0.06; P < 0.05) and serum triglycerides (2.26 +/- 0.14 vs. 1.99 +/- 0.21; P < 0.05) during the course of the study. Other lipid parameters did not change, although there was a trend towards improvement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196295 TI - Acute hemodialysis of infants weighing less than five kilograms. AB - The records of 33 infants weighing 5 kg or less who received acute hemodialysis treatment at Children's Hospital between 1980 and 1991 were reviewed. Dialysis was initiated to treat hyperammonemia (8), primary renal or renovascular disease (7), and acute renal failure (18). The infants weighed 2.2 to 4.0 kg at birth and 27% were born prematurely. The infants were 2 to 120 days of age (median 10 days) and weighed 2.2 to 5.0 kg (median 3.5 kg) at the initiation of hemodialysis. Hemodialysis access was achieved via double-lumen 7 French catheters in 49% of the infants, the ECMO circuit in 24%, and the umbilical vessels in 27%. Thirty three infants underwent a total of 216 hemodialysis treatments. Only nine treatments were discontinued prematurely: six for intractable hypotension and three for technical problems. Fifty-two percent (17 of 33) of the infants survived through the end of the hemodialysis treatment course. The survival rates for the infants with hyperammonemia (75%) and primary renal disease (71%) were better than those for infants with acute renal failure (33%). The survivors did not differ from those who died with respect to birthweight, weight when hemodialysis was initiated, or the number of hemodialysis treatments administered. We conclude that infants weighing less than 5 kg can be treated successfully with hemodialysis. Patient survival is related to underlying medical problems, not to complications of hemodialysis. PMID- 8196296 TI - Socioeconomic status and end-stage renal disease in the United States. AB - The incidence of treated end-stage renal disease (ESRD) varies markedly according to age, race, sex, and geographic characteristics of the population. We asked whether some of the variability in the incidence of treated ESRD (t-ESRD) was associated with differences in socioeconomic status and whether socioeconomic status could explain some of the effects of race on t-ESRD incidence. Demographic characteristics of incident cases of t-ESRD from the years 1983 to 1988 were obtained from the U.S. Renal Data System, which registers most treated cases of ESRD. The average race specific, per capita income of the county of residence, as determined from the Bureau of Health Professions Area Resource File, was used as a surrogate measure of socioeconomic status. the incidence of t-ESRD for individuals < 60 years of age was modeled as a log-linear function of socioeconomic and demographic factors, including age, sex, the urban fraction of the county of residence, and the census geographic region. For both Whites and Blacks, the incidence of t-ESRD was higher for males and older age groups, as expected. In general, the incidence of t-ESRD was inversely related to income level. For Whites, the relative risk was 1.21 for income of $0 to 10.000, 1.11 for $10,000 to 15,000, 1.00 for $15,000 to 20,000 (reference), 0.89 for $20,000 to 25,000, and 0.77 for income > $25,000. For Blacks, the relative risk was 1.10 for income of $0 to 10,000, 1.20 for $10,000 to 15,000, 1.00 for $15,000 to 20,000 (reference), 0.81 for $20,000 to 25,000, and 0.69 for income > $25,000.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196297 TI - Adaptive control of anticoagulation during hemodialysis. PMID- 8196298 TI - Sustained expression of TGF-beta 1 underlies development of progressive kidney fibrosis. AB - We found that TGF-beta 1 expression and increased matrix production is transient and self-limited in nephritic glomeruli from rats with acute, reversible glomerulonephritis induced by a single injection of an antibody reactive with glomerular mesangial cells. In contrast, in rats given a second antibody injection, one week later, the glomerular expression of TGF-beta 1 mRNA and TGF beta 1 protein remained elevated through 18 weeks and was associated with a large infiltration of mononuclear cells, with staining features of fibroblastic/myofibroblastic cells, strongly expressing TGF-beta 1 in the tubulointerstitium of the kidney. By 18 weeks kidneys from animals receiving two antibody injections showed glomerulosclerosis and tubulointerstitial fibrosis with striking deposition of collagens type I and III, whereas kidney tissue from animals given one antibody injection was indistinguishable from normal control. The histological changes were accompanied by persistent proteinuria and elevated levels of blood urea nitrogen. Extracellular matrix markers of TGF-beta 1 activity, a special isoform of fibronectin, tenascin, biglycan and plasminogen activator inhibitor-1, were significantly elevated in kidneys undergoing fibrosis. These data suggest that sustained TGF-beta 1 expression contributes to the development of progressive kidney fibrosis. PMID- 8196299 TI - Lupus nephritis: lessons from the path lab. PMID- 8196300 TI - [Use of a new anomaloscope test in diagnosis of glaucoma]. AB - BACKGROUND: The Color Vision Meter 712 (CVM) is a new automatic computerized anomaloscope relying on both the Rayleigh and the Moreland equation. In the present study the diagnostic value of Color Vision Meter was examined in glaucoma for the first time and was compared with the Farnsworth 100 hue test. PATIENTS AND METHODS: 33 normals, 15 patients with ocular hypertension (OHT) and a heterogenic group of 31 glaucoma patients were tested with the Nagel anomaloscope, the Color Vision Meter 712 and the Farnsworth 100 hue test. The following determinations were made in all subjects: 1. Anomalous quotient of the Rayleigh equation of the Nagel anomaloscope and of the Color Vision Meter, 2. Mean tritan score of 100 hue test, 3. The matching range, mid matching point, and anomalous quotient of the Moreland equation with the Color Vision Meter. RESULTS: While in the OHT group only the matching range of the Moreland equation was enlarged, all three variables (matching range, mid matching point and anomalous quotient) of the Moreland equation were significantly changed in the glaucoma group. The mean tritan score of the 100 hue test showed in the OHT group only a slight difference compared to normals, and in the glaucoma group a low significance and a low sensitivity. The matching range of the Moreland equation seems to be most useful with a sensitivity of 87.1% and a specificity of 93.6%. CONCLUSION: Our results show that the new anomaloscope Color Vision Meter 712 should be considered as a quick screening test for the examination of blue-color vision disturbances in glaucoma because of its higher sensitivity, its easier use for examiner and patients, and its shortened examination time (5 min per equation). PMID- 8196301 TI - [Autologous transplantation of nasal mucosa after severe chemical and thermal eye burns]. AB - BACKGROUND: Extensive conjunctival scarring is common after severe chemical and thermal eye burns. There is often not enough healthy conjunctiva from the other eye available to correct the symblepharons, therefore other autologous tissues have to be transplanted. PATIENTS AND METHODS: From February 1992 until March 1993 13 patients were treated with free nasal mucosal grafts from the inferior turbinates for reconstruction of the fornices. The newly created deep fornices were secured by a silicone band. In 3 patients an Illig plastic shell was used additionally. The surgical treatment was supplemented with an intensive treatment with topical corticosteroids to decrease the inflammatory reaction. RESULTS: The patients were followed for an average of 7-18 months. The interval between the accident and the transplantation ranged from 2-26 months. In 10 patients a reconstruction of the fornices was achieved. In all patients, however, some slight scars could be observed. Postoperative Schirmertest was markedly improved. These results encourage us to plan a penetrating keratoplasty in 7 cases. 3 patients showed a recurrence of the symblepharon 2 months after the transplantation. CONCLUSION: The nasal mucosa graft material is best suited for repair of extensive symblepharon. The advantages of this tissue are the availability of large pieces of mucosa and the transplantation of intraepithelial goblet-cells. Long-term effects are the improvement and stabilisation of the tear film. PMID- 8196302 TI - [Therapy of dry eye disorders]. AB - BACKGROUND: The treatment of dry eyes with artificial tears often fails. We differentiated the disturbances of the three layers of the tear film in 90 such patients. This showed that only 11.1% had aqueous deficiency, while 42.3% had combined disturbances of different layers of the tear film, and 76.7% had lipid deficiencies. PATIENTS AND METHODS: We now studied the efficacy of a therapeutic approach, which intended to stabilize each individual deficiency of the three layers of the tear film (follow-up > or = 6 months). The medical history, visual acuity, slit lamp examination, rose bengal stains and fluorescein stains, Schirmer test, break-up time (BUT), dye tests, impression cytology, and lid transillumination were analyzed. RESULTS: Therapy was beneficial in all patients (n = 90) with regard to the symptoms and the objective parameters. Artificial tears applied strictly were without preservatives. Patients with toxic conjunctivitis induced by high dosages of eye drops were often stabilized through withdrawing the medication. The frequency of applying artificial tears was significantly tapered by punctum plugs and -coagulation. Tarsorrhapies were helpful in the most severe cases. Topical retinoids significantly reduced the symptoms and increased the goblet cell density. Treating chronic blepharitis was very sufficient, when initiated by topical steroids and Tetracycline, and systemical Doxycycline. CONCLUSIONS: Differentiating the disturbances of the three tear film layers in "sicca syndrome", and stabilizing each component is more effective than artificial tears alone. PMID- 8196303 TI - [Pholedrine for determining the site of Horner syndrome]. AB - BACKGROUND: Pharmacologic testing by indirect acting sympathomimetics like hydroxyamphetamine may determine the site of the lesion in Horner's syndrome. Pholedrine is chemically similar to hydroxyamphetamine. Therefore we examined if it shows the same effects in normal subjects and in patients with Horner's syndrome. METHODS: Pupil diameter was measured by means of standardized photography before and after single and with different intervals repeated administration of pholedrine eye drops in normal subjects. In 18 patients with Horner's syndrome and known hydroxyamphetamine test results, a pholedrine test was carried out analogous to the hydroxyamphetamine test. RESULTS: Pholedrine dilates the normal pupil by 2.2 mm (mean). It acts at the longest 8-10 hours with maximal effect between 20 and 90 minutes. After this period its effect decreases rapidly. It acts independently from age and from baseline pupil diameter. Given repeatedly the second administration reaches the same mydriatic effect as the first only if the interval between both applications is 72 hours or more. This is because it needs some time to refill the noradrenaline stores in the sympathetic neuron innervating the dilator muscle of the pupil. In Horner's syndrome pholedrine dilates the involved pupil only minimally in case of a postganglionic lesion, and in case of a preganglionic lesion it dilates the pupil even slightly more than the normal fellow pupil. It shows the same effect as hydroxyamphetamine. There are only few side effects. CONCLUSION: Pholedrine is a substitute for hydroxyamphetamine to localize the site of the lesion in patients with Horner's syndrome. PMID- 8196304 TI - [Diplopia after retrobulbar anesthesia in cataract surgery--a case report]. AB - A case report. A homolateral hypertrophia accompanied by diplopia occurred after retrobulbar anesthesia for cataract operation. In the course of the next few months a hypotrophia developed in the same eye. Two and a half years later a 5 mm recession of the inferior rectus muscle of the hypotrophic eye was performed under local anesthesia. The passive motility upwards improved already during the operation when the muscle was sectioned. After the operation there was a remarkable improvement of motility and field of vision. Conclusion. The cause of this diplopia is probably an injury of the inferior rectus muscle with a secondary contraction caused by the retrobulbar anesthesia. An injection along the inferior rectus muscle to achieve the retrobulbar anesthesia should be avoided. PMID- 8196305 TI - [Examination procedure in automated determination of far and near vision]. AB - BACKGROUND: Although the measurement of visual acuity at distance is more important in ophthalmological practice, the visual acuity at near should be tested additionally. In a recently published paper we showed that with today's computer technology visual acuity at distance can be measured in standardized procedures according to DIN 58220. We describe here an additional, integrated setup, which allows the measurement of visual acuity also at near. METHODS: For testing visual acuity at near, the whole set of optotypes is presented on a transparent overlay mask in front of a computer monitor which is used as a program-controlled light source. A certain optotype is chosen by illuminating its background. The patient's responses are read via a small console by the computer. The test procedure follows the DIN requirements. RESULTS AND CONCLUSIONS: First reliability tests showed that the test arrangement is qualified for rapid and standardized determination of visual acuity at near and at distance under nearly natural viewing conditions. PMID- 8196307 TI - Epidemiology of invasive Haemophilus influenzae disease in a German city. AB - This study was done to analyze the epidemiology of invasive Haemophilus influenzae disease in Bochum city area. Forty-eight children with invasive Haemophilus influenzae infections were treated at the University Children's Hospital in Bochum during the study period from January 1971 to June 1992. Clinical manifestations included meningitis (n = 34), epiglottitis (n = 8), pneumonia (n = 2), bacteremia (n = 2), cellulitis (n = 1) and osteomyelitis (n = 1). The overall yearly incidence rate for all invasive Haemophilus influenzae infections was 13 per 100,000 children younger than five years of age, with a marked increase in the last six years. Haemophilus influenzae meningitis showed no significant change during the study period with an overall yearly incidence of 9 per 100,000 children younger than five years. Twenty-eight cases (58%) of all invasive Haemophilus influenzae infections occurred in patients under two years of age and five cases (10%) were younger than six months. Invasive Haemophilus influenzae disease showed no seasonal prevalence. All isolates were susceptible to ampicillin. No deaths occurred, but severe bilateral deafness resulted in one patient with meningitis. Prospective epidemiologic studies are needed to estimate clinical efficacy of the Haemophilus influenzae type b immunization program in Germany. PMID- 8196306 TI - [EEG in diagnosis of other disease pictures than epilepsy]. AB - Electroencephalography plays a very important role in the diagnosis and course monitoring of epilepsy. The EEG is also able to give decisive clues in diseases other than epilepsy. It is important to know these specific EEG patterns which may assume a key role in the diagnosis of rare neuropediatric diseases. Familiarity with such specific patterns will allow to select only specific investigations for diagnostic confirmation. We report six guiding EEG patterns and the associated disorders: 1. Re-build up phenomena for Moyamoya syndrome. 2. High amplitude alpha-beta activity for lissencephaly type I. 3. Positive spikes during low frequency photostimulation for late infantile neuronal ceroid lipofuscinosis. 4. Periodic high amplitude discharges for subacute sclerosing panencephalitis (SSPE). 5. Burst suppression pattern in non-asphyctic mature newborns for Ohtahara syndrome, non ketotic hyperglycinemia or molybden cofactor deficiency. 6. High amplitude 3-4 HZ activity with small spikes for Angelman syndrome. PMID- 8196308 TI - [Typical complications of short rib polydactyly syndrome]. AB - Osteochondrodysplasias are hereditary dysfunctions of the enchondral ossification with a decreased longitudinal bone-growth. We describe the case of a female child which suffered from a short rib-polydactyly-syndrome, a localised form of a osteo chondrodysplasia, and died at the age of nine months as a result of the typical complications of this disease. PMID- 8196309 TI - [Retinopathy of prematurity: an analysis of risk factors]. AB - In 29 infants with retinopathy of prematurity we retrospectively studied the influence of various clinical factors on the severity of the disease and compared this group of patients with controls without retinopathy. Infants presenting with different stages of retinopathy showed significant differences in gestational age, length of mechanical ventilation, additional supplemental oxygen, and the number of episodes of acidosis and hypocarbia. Compared with controls, hyperoxemia with paO2-levels above 100 mmHg and hypocarbia with pCO2-levels below 35 mmHg was more often observed in infants with retinopathy (p < 0.05, respectively p < 0.01). Besides, these infants were more often treated with surgical ligation of a patent ductus arteriosus than with indomethacin (p < 0.001). In our patients we were not able to assess the incidence and the severity of retinopathy of prematurity by calculation of risk scores or safety indices. PMID- 8196310 TI - [Click-evoked otoacoustic emissions and acoustic brain stem potentials in early detection of hearing disorders in premature and newborn infants after neonatal critical care]. AB - Evoked otoacoustic emissions (EOAE) and brainstem acoustic evoked potentials (BAEP) were recorded from 78 children following neonatal intensive care. In 23% no EOAE could be obtained. Hearing impairment in the BAEP was found in 9%. In 22% negative EOAE were found in spite of normal BAEP. According to the latency intensity function of waves I and V all children with abnormal BAEP were classified having a conductive hearing loss. In accordance in no case a narrowing of the emission spectrum could be found in the EOAE. In both methods the rate of hearing impairment was highest in children with birth weights of less than 1000 g. A screening of all infants after neonatal intensive care using EOAE is recommended. BAEP should be done additionally in cases with deficient EOAE. PMID- 8196311 TI - [High frequency oscillation in meconium aspiration and bronchopulmonary dysplasia]. AB - Within one year 3 newborns with meconium-aspiration and 4 infants with bronchopulmonary dysplasia (BPD) were treated with HFP, synchronous with conventional ventilation (CMV). The entrance criteria were insufficient oxygenation (PO2/FiO2 < 50 mmHg) and/or CO2-elimination (> 60 mmHg), respectively peak inspiratory pressure Pi > 40 mmHg and mean airway pressure MAP > 20 mbar during CMV. All three cases of meconium-aspiration have shown a striking improvement in oxygenation and ventilation, in one case starting from a disastrous situation with PCO2 > 90 mmHg, PO2 30 mmHg (FiO2 100%). After a HFO period of 9 to 10 hours Pi, MAP and CMV-frequency could be reduced. The patients could be extubated after 1-2 weeks. In severe BPD only in one case continuous improvement and extubation in the 4. week of life were possible. Here the pulmonary artery pressure in doppler-echocardiography slightly was elevated (30 35 mmHg). In a further case extubation was possible after several trials with HFO. Indeed chronic respiratory insufficiency, progredient pulmonary emphysema on x-ray and clearly elevated pulmonary artery pressure (> 40 mmHg) persisted. In 2 further cases there was no longstanding improvement of ventilation. One child died after 8 months, one after 6 months. In both cases there was a right-to-left shunt over foramen ovale and pulmonary artery pressures at systemic level. HFO led to an improvement in oxygenation and ventilation in all three cases of meconium-aspiration and probably prevented a fatal outcome in one case. The effect seems to depend on improved secretolysis and gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196312 TI - [Measuring cardiac output in infants with the Fick principle via oxygen consumption: animal experiment and clinical results]. AB - The aim of this investigation was the validation of cardiac output measurement in children using the method of Fick with the help of a new equipment for the determination of oxygen uptake. METHODS: We compared the cardiac output measured with thermodilution with the calculated cardiac output using the method described by Fick in an animal model (11 dogs, mean weight 20 kg). For determining the cardiac output on Fick's principle oxygen uptake and oxygen content of the arterial and pulmonary-arterial blood was measured in the ventilated dogs. To examine the method of Fick in clinical routine we also determined oxygen uptake and arterial and central venous oxygen content in 5 children in the postoperative period after cardiac surgery with a mean weight of 8.5 kg. Cardiac output in the patients was calculated with the central venous and the pulmonary-arterial oxygen content. The two results were compared. RESULTS: The animal model showed a good correlation of cardiac output measurement on thermodilution and on Fick's method (alpha = 0.001, t-test of significance of correlation). With the method of Fick we found also reliable results at follow up in the clinical routine in the 5 children. The comparison of cardiac output calculated with the central venous oxygen content versus the pulmonary-arterial oxygen content shows a good correlation over all (r = 0.92). In some cases however we found profound differences. PMID- 8196313 TI - [Successful treatment of therapy refractory shock lung in a newborn infant with congenital varicella using extracorporeal membrane oxygenation]. AB - A newborn with congenital varicella complicated by varicella pneumonia was transferred to our hospital on day 16 of life for the consideration of extracorporeal membrane oxygenation (ECMO). The newborn received varicella zoster immunoglobulin 13 hours after birth since the mother developed a varicella exanthema two days before delivery. On day 10 of life the newborn became clinically symptomatic with red macules and pustules. The chest roentgenogram revealed reticular pulmonary infiltrates in the right upper lobe. Antibacterial chemotherapy was initiated. In the following days the cutaneous lesions progressed, and respiratory symptoms like tachypnoea and oxygen dependence occurred. Chest roentgenograms revealed diffuse reticular and patchy pulmonary infiltrates. On day 14 of life antiviral chemotherapy with acyclovir was started. ECMO was initiated in the veno-arterial mode on day 17 due to severe respiratory failure despite maximal conventional assisted ventilation and carried out for 14 days. With the age of 10 weeks he was discharged from the hospital with mild chronic lung disease without oxygen requirements and without neurological handicap. ECMO might be considered as life saving support in newborns with severe congenital varicella, considered to have a high mortality risk. PMID- 8196314 TI - [Simultaneous determination of inorganic anions in body fluids. A new method in pediatric laboratory diagnosis--results of a pilot study]. AB - The anions analysis was a methodical problem up to now. This was the reason for low interest. Biological fluids like saliva and urine which could easily receive without any stress for the children, are little investigated for its capacity on nitrite, nitrate, bromide and sulfate. In this performance there will presented an ion-chromatographic method to determine inorganic anions in the following body fluids: serum saliva, liquor and urine. The anions chloride, nitrite, bromide, nitrate, phosphate and sulfate was determined quantitatively. The method was proved in a pilot-study on children's body-fluids serum, liquor and saliva. The objects was to get a landmark in expectation from anion concentrations. Bromide was detected as a constant part in all body fluids. The origin and importance is not clear till now. Also was found nitrate in all investigated body fluids. There seems to be a connection between diarrhea and an increase in serum levels from nitrate. We found considerable amounts of nitrate in saliva by babies and infants. The method is distinguished by little fluctuation in measurement and high specificity. Short time in analysis and simple handling will do the method for a qualified one in pediatrics. PMID- 8196315 TI - [Use of thymus hormones in allergy]. PMID- 8196316 TI - [Some aspects of pathogenetic therapy of diabetic angiopathies]. PMID- 8196317 TI - [Clinical and pathogenetic significance of the antioxidative system in infectious diseases]. PMID- 8196318 TI - [Use of fragmin (low-molecular-weight heparin) in patients with unstable angina]. PMID- 8196319 TI - [Gas therapy in pulmonology]. PMID- 8196320 TI - [Acute pneumonia in oncology patients: problems of epidemiology]. AB - Autopsy findings, analyzed retrospectively for 2564 cancer patients showed the presence of acute pneumonia in 47.43% of them (50.82% in males against 43.21% in females). When compared to noncancer controls, this difference proved significant. No correlations were noted between the incidence and extension of acute pneumonia and various sites of the tumor, between metastases, emergence and extension of the disease. Among pneumonia types focal, focal-confluent forms with involvement of the lower right lobe predominated. As for complications, pleurisy was the most common finding. PMID- 8196321 TI - [Gemfibrozil in the treatment of lipid metabolism disorders]. AB - The study was made of gemfibrozil tolerance and effectivity against atherosclerosis and in correction of lipid metabolism in 20 patients with hyperlipidemia. (11 males and 9 females, a mean age 51 +/- 3.1 years). The assessment of the treatment efficacy was performed clinically, biochemically, using bicycle ergometry exercise. Eight weeks of gemfibrozil treatment in a dose 12-1.8 g/day produced a hypolipidemic effect in 90% of the patients which were mostly of IIb and IV genotypes. The highest efficacy was reported in lowering triglycerides, VLDL cholesterol. In less extent the drug reduced LDL cholesterol. Some of the patients became hypolipidemic by HDL cholesterol. It is concluded that in hyperlipidemic patients gemfibrozil improves the running of atherosclerosis without the effect on angina pectoris. PMID- 8196322 TI - [Calcium antagonists in the therapy of ischemic heart disease]. PMID- 8196323 TI - [Clinical evaluation of aiconol side effects]. AB - In the study of 164 patients with atherogenic dyslipidemia the authors studied side effects of aiconol, concentrated cod liver oil. Its lipid component contains not less than 18% of omega-3 polyunsaturated fatty acids (PUFA). All the patients were divided into 4 groups: 51 subjects of group 1 received aiconol in the form of oil, 35 subjects of group 2 had protein dietetic caviar prepared from animal proteins with addition of 3% aiconol, 38 subjects of group 3 were given protein oil emulsion containing 20% aiconol and 40 patients of group 4 took gelatin aiconol in capsules. Side effects of the above food ingredients enriched with omega-3 PUFA were found to be of metabolic nature. These manifested most evidently in patients on oil aiconol incorporating both maximal doses of omega-3 PUFA and the largest amounts of inert constituents acting as additional fat load on the liver and pancreas. Group 1 patients also suffered from aggravated chronic gastrointestinal, hepatic and pancreatic disorders. Because of reduced quantities of omega-3 PUFA in the diets of group 2, 3 and 4 patients, they displayed much less severe side effects. PMID- 8196324 TI - [Heart disorders in Lyme disease]. AB - The paper presents literature data on clinical manifestations, instrumental diagnosis and pathohistological changes in Lyme carditis. Three cases were analyzed. The emphasis is placed on the necessity of differential diagnosis with Lyme disease in all the cases of unclear myocarditis and cardiac arrhythmia, especially in the territories endemic for tick-borne diseases. PMID- 8196325 TI - [Clinical and diagnostic value of prostaglandins E determination in patients with ulcer]. AB - The authors investigate the relevance of ulcer clinical variants (recent ulcer, of 10 years history and 2-3 annual exacerbations, chronic ulcer with aggravations and incomplete remissions) to production of endogenic PGE by gastric mucosa and to blood PGE level. It is shown that with ulcer progression PGE synthesis activization is replaced by its inhibition. A reverse relationship appeared between gastric juice and blood PGE and duration of ulcer. Etiopathogenetic heterogeneity is suggested in the group with complicated ulcer. PMID- 8196326 TI - [Nodular panniculitis (Weber-Christian disease)]. PMID- 8196327 TI - [Development of xanthomatosis in a patient with diabetes insipidus]. PMID- 8196328 TI - [Use of cyclophosphane pulse-therapy in the treatment of severe nonspecific ulcerative colitis]. PMID- 8196329 TI - [Treatment of patients with initial manifestations of cerebrovascular insufficiency in atherosclerosis]. PMID- 8196330 TI - [Use of coldact, a long-acting preparation of NATKO for the treatment of upper respiratory tract diseases in outpatient clinics]. PMID- 8196331 TI - [Errors and difficulties in the diagnosis of lung cancer]. PMID- 8196332 TI - [Tubulointerstitial kidney impairement in nephrology practice]. PMID- 8196333 TI - [Theoretical aspects of fever. Fever etiology]. PMID- 8196334 TI - [Atrial natriuretic factor in patients with arterial hypertension]. PMID- 8196335 TI - [Hospital Uster: the infamous chronology of the year 1993. Solidary pay reductions not considered]. PMID- 8196336 TI - [Growing on complex nursing situations]. PMID- 8196337 TI - [Research from practice--for your work]. PMID- 8196338 TI - [Visit of the German Association of Nursing Professions in eastern Europe. Nursing in Estonia]. PMID- 8196340 TI - [Death row prisoners as organ donors in Taiwan]. PMID- 8196341 TI - [How solidarity can change a difficult situation]. PMID- 8196339 TI - [Trip by the Swiss Nursing Association to Russia--a report. A glimpse into Russian hospitals]. PMID- 8196342 TI - [Experiences in a specialized service. Office hours for "diabetic foot"]. PMID- 8196343 TI - [The concept of continuity of care. The effectiveness of long-term support]. PMID- 8196344 TI - [Forum of clinicians and clinical specialists. High-level professionals]. PMID- 8196345 TI - [The case of the Mexican guest workers in the United States. How to integrate their popular beliefs]. PMID- 8196346 TI - [Economical balance shows: permanent products are better for the environment]. PMID- 8196347 TI - [Care of severely dependent demented patients. Decision for ethics--but for which version?]. PMID- 8196348 TI - [Ambulatory facility for substance dependents--a model facility in Basle. Methadone--the potential alternative]. PMID- 8196349 TI - [Nurses as patients. The view from the bed]. PMID- 8196350 TI - [Studies in clinics and schools. Patient care planning between theory and practice]. PMID- 8196351 TI - [Action "Nurses for Nurses". Evidence in Yugoslavia]. PMID- 8196352 TI - [Feeling responsible for the patient--key to a good relationship]. PMID- 8196354 TI - [Change ... to a program based on a conceptual model]. PMID- 8196353 TI - [Public health nurses: "Your future is in your hands"]. PMID- 8196355 TI - [Nutrition education in school. Good appetite, my dear]. PMID- 8196356 TI - [The multiple facets of hypnosis]. PMID- 8196357 TI - Molecular markers of melanocytic tumor progression. PMID- 8196358 TI - Mechanism of the induction of autoimmune disease by graft-versus-host reaction. Role of CD8+ cells in the development of hepatic and ductal lesions induced by CD4+ cells in MHC class I plus II-different host. AB - BACKGROUND: We previously reported that primary biliary cirrhosis (PBC)-like hepatic lesions were induced in (bm12xB6)F1 mice undergoing graft-versus-host reaction with major histocompatibility complex class II disparity. In this paper, we report on a new experimental system, enabling establishment of more progressed stages of PBC-like lesions and clarification of the role of CD8+ cells in the development of the lesions. EXPERIMENTAL DESIGN: Recipient (bm12xbm1)F1 mice were thymectomized and administered anti-Lyt-2 monoclonal antibodies intraperitoneally to deplete host CD8+ cells as completely as possible. The treatment was necessary to induce autoimmune hepatic lesions in this type of F1 mice. Recipients were divided into five groups: group 1 received B6 CD4+ cells on day 0 and 2 weeks later, B6 CD8+ cells; group 2, only B6 CD4+ cells on day 0; group 3, only B6 CD8+ cells on day 14; group 4, B6 CD4+ on day 0 plus F1 CD8+ cells 14 days later. Cell transfer was not done in group 5. All of the mice were killed on day 28 for examination by light and electron microscopy and also by immunohistochemistry. RESULTS: PBC-like hepatic lesions without tissue destruction were induced in the mice of group 2, as was previously reported. In addition to similar lesions to group 2, destruction of hepatocytes and bile duct epithelia was induced in the mice of group 1. Weak lymphocytic infiltration and periductal concentric fibrosis were observed in the mice of group 3. PBC-like hepatic lesions without tissue destruction were induced in mice of group 4 as were those of group 2. However, the cellular infiltration was much weaker. CONCLUSIONS: For the animal model of PBC, we have devised a new experimental system in which the role of donor or host type CD8+ cells is assessable. Tissue-destructive lesions were induced only in mice that received donor CD4+ cells followed by CD8+ cells. The PBC-like lesions were suppressed by host type CD8+ cells. These results suggest that destructive hepatic lesions of PBC might progress through CD8+ cells in cooperation with CD4+ cells, and that host type CD8+ cells could act as "regulatory" T cells for the progression of the lesions. PMID- 8196359 TI - Enhanced expression of transforming growth factor-beta s and transforming growth factor-beta type II receptor in the synovial tissues of patients with rheumatoid arthritis. AB - BACKGROUND: A growing body of evidences suggests that transforming growth factor beta (TGF-beta) is produced in the synovial fluid of patients with rheumatoid arthritis (RA), and that TGF-beta is an important regulator in the course of the disease. Careful studies on the endogenous synthesis of TGF-beta as well as its receptors are therefore necessary to clarify the possible role of TGF-beta in RA. EXPERIMENTAL DESIGN: We examined the expressions of latent TGF-beta 1, -beta 2, and -beta 3, the latent TGF-beta 1-binding protein (LTBP) as well as TGF-beta type II receptor (TGF-beta RII) in the synovial biopsy tissues of 21 patients with RA by immunohistochemistry. Five specimens from these cases representing both active and chronic inactive stages were also examined for the corresponding mRNA by in situ hybridization. Northern blot analysis was performed on 3 synovial membranes taken from the RA patients together with a control synovium. RESULTS: Abundant LTBP, TGF-beta 1, and TGF-beta RII-positive cells as well as less intensively stained TGF-beta 2 and TGF-beta 3-positive cells were found in the synovial layer. These cells were positive for the histocompatibility antigen, HLA DR. In lymphocyte aggregates, scattered cells positively labeled for LTBP and TGF beta 1 were found. They stained in a reticular pattern that was similar to that demonstrated by an antibody against human dendritic cells, and also expressed HLA DR. In situ hybridization revealed markedly increased signals for LTBP and TGF beta RII mRNA in tissues with an active inflammatory process, when compared with tissues with less active inflammation. However, no clear differences in the levels of expression for any of the TGF-beta isoforms were found. Specimens with pronounced fibrosis, fibroblasts, and surrounding collagen fibers expressed positive immunoreactivities for all TGF-beta isoforms and LTBP. Northern blot analysis on 4 synovial tissues demonstrated positive signals for LTBP and TGF beta 1 mRNA in all three RA patients in contrast to a normal control, which did not show any signals. An increased expression of TGF-beta RII mRNA was detected in the tissue from one of the patients. CONCLUSIONS: An abundant expression of TGF-beta 1 and LTBP, as well as TGF-beta RII was seen in most actively proliferating synovial intimal cells, and the level of the expression varied during the course of the disease. We conclude that TGF-beta is involved tightly in the regulation of the inflammatory process, and it is thus possible that the endogenous TGF-beta functions as a self-regulator that induces the remission periods. PMID- 8196360 TI - Experimental IgA nephropathy. Enhanced deposition of glomerular IgA immune complex in proteinuric states. AB - BACKGROUND: IgA nephropathy is induced by the IgA-immune complex (IC). IgA nephropathy associated with heavy proteinuria is considered a more progressive form of the disease. To elucidate the mechanism by which the latter condition occurs, we investigated the effect of proteinuria on the glomerular deposition of IgA-IC. EXPERIMENTAL DESIGN: BALB/c female mice that had been made proteinuric by adriamycin or bovine serum albumin (BSA) were injected with TEPC-15 hybridoma derived IgA anti-phosphorylcholine (PC) and individual specific antigens. The 6 hour clearance kinetics of IgA were measured, and the accumulation of IgA deposits and the third complement component (C3) in the glomerulus were analyzed. RESULTS: The clearance kinetics of 125I-IgA injected together with a specific antigen, PC-conjugated BSA (BSA-PC), showed only a minimal distinction between the experimental (proteinuric) and the control (nonproteinuric) groups of mice. However, analysis of renal tissue by immunofluorescence and light microscopic autoradiography revealed markedly enhanced mesangial IgA-IC deposition in the proteinuric mice receiving IgA and one of three specific antigens, BSA-PC, PC conjugated cytochrome-c, and a pneumococcal C-polysaccharide. Immunofluorescence also showed augmented mesangial C3 deposition in proteinuric mice that received IgA/PC-conjugated cytochrome-c or IgA/pneumococcal C-polysaccharide. In addition, adriamycin or BSA per se did not influence glomerular IgA-IC localization. CONCLUSIONS: Glomerular localization of nephritogenic IgA-IC was comparably enhanced in mice with proteinuria induced by various methods. Thus, a vicious cycle for the progression of IgA nephropathy might ensue in proteinuric states. PMID- 8196361 TI - Cell polarity in human renal cystic disease. AB - BACKGROUND: In polycystic kidney disease (PKD), altered cellular polarity with mislocation of Na/K-ATPase, and net fluid secretion may have a role in cyst development and progression. EXPERIMENTAL DESIGN: Cell polarity was assessed in surgically excised human normal, autosomal dominant PKD, and acquired PKD occurring in end stage renal disease on long-term dialysis kidneys quick frozen (< 5 minutes) or fixed to minimize ischemic changes. RESULTS: Findings were similar in autosomal dominant PKD and acquired PKD kidneys. By ultrastructure, in cysts, cells were polarized, however, their basement membranes were greatly thickened and reticulated. By immunohistology, in cell-lining cysts, Na/K-ATPase, fodrin, and ankyrin were localized primarily to basolateral cell membranes and uvomorulin was localized to lateral cell membranes. In about 25% of the cells, however, Na/K-ATPase was localized to the apical as well as the basolateral membranes. Both in autosomal dominant PKD and normal kidney cell monolayers in vitro, cationic ferritin was normally absorbed by apical endocytosis, and transferred to apical vacuoles and phagolysosomes. CONCLUSIONS: These findings indicate intact structural and functional polarity in cell-lining cysts; however, in about 25% of the cells, Na/K-ATPase, fodrin, and ankyrin are localized to apical and lateral cell membranes, probably due to cell dedifferentiation. The notable changes in the basement membranes of cysts suggest a key role for the extracellular matrix in the pathogenesis of PKD. PMID- 8196362 TI - Defect of nephrogenesis induced by gentamicin in rat metanephric organ culture. AB - BACKGROUND: In the rat, in utero exposure to gentamicin during early renal differentiation leads to a permanent nephron deficit. The aim of the present study was to analyze, in vitro, the potential direct effect of gentamicin on early nephrogenesis. EXPERIMENTAL DESIGN: We used paired rat metanephric organ cultures from 14 (F14) or 15-day-old (F15) fetuses. We measured gentamicin accumulation into explanted metanephroi and then assessed in vitro growth in the absence or presence of the drug. Glomerular labeling and counting were performed on the whole explant to analyze the effect of antibiotics on early nephrogenesis. RESULTS: Growth of F14 metanephric explants in the presence of 50 micrograms of gentamicin/ml was significantly reduced from 4 days onwards as compared to controls, whereas F15 explants grown with gentamicin displayed a normal in vitro development. After 6 days of culture, F14 and F15 explants had the same accumulation of gentamicin (1 microgram/mg protein) but the gentamicin content was 4 times larger in F15 explants. At both ages, gentamicin-exposed metanephric explants exhibited a significant reduction in their number of nephrons. However, the effects of 50 micrograms of gentamicin/ml on nephrogenesis were significantly more drastic on F14 than F15 explants (35% versus 18%). When grown with 0.5 microgram of gentamicin/ml, F14 explants still exhibited a 16% defect in nephrogenesis as compared with controls, and about the same reduction was observed for cultures in the presence of 100 micrograms/ml of streptomycin and 100 IU/ml of penicillin. Incubation of F14 explants with streptomycin alone for 6 days had no effect on nephrogenesis. CONCLUSIONS: These results indicate that gentamicin induces a significant reduction in the number of nephrons in metanephric explants and that this effect is more important on less differentiated metanephroi. Metanephric organ culture combined with glomerular labeling represents a useful model to test the effect of various growth factors and other drugs on early nephrogenesis. PMID- 8196363 TI - Inhibition of experimental autoimmune neuritis by an antibody to the lymphocyte function-associated antigen-1. AB - BACKGROUND: Experimental autoimmune neuritis (EAN) is an animal model of Guillain Barre syndrome. The mechanisms underlying cellular trafficking and homing of autoreactive immune cells to the peripheral nervous system during EAN and Guillain-Barre syndrome are unknown. We investigated the role of the adhesion molecule lymphocyte function-associated antigen-1 in the pathogenesis of EAN. EXPERIMENTAL DESIGN: EAN was induced in Lewis rats either by immunization with bovine spinal root myelin or by adoptive transfer of P2-specific T cells. Animals were treated intraperitoneally with a monoclonal antibody to lymphocyte function associated antigen-1 (WT-1) or phosphate-buffered saline and scored for clinical signs. Histology was performed on sciatic nerve and cauda equina and assessed for infiltration and demyelination. Severity of EAN and the corresponding histologic alterations were compared in the different treatment groups. The in vitro effect of WT-1 on T cell proliferation was evaluated. RESULTS: Treatment with WT-1 prevented or efficiently suppressed myelin-induced EAN. In contrast, sham treatment of animals failed to alter the clinical course of EAN. Histologic examination of the peripheral nervous system showed a marked reduction of inflammatory infiltration and perivascular demyelination in animals treated with WT-1. Adoptive transfer EAN was not affected by the administration of WT-1. The differential action in the two models suggests that WT-1 appears to act primarily on the induction phase of the immune response but has no significant impact on the effector phase. In vitro studies with WT-1 revealed that the antibody inhibits the concanavalin A-dependent proliferation of neuritogenic P2-specific T cells. CONCLUSIONS: Our data indicate that lymphocyte function-associated antigen 1 is critically involved in the pathogenesis of EAN. Further analysis of this model may provide insight into the process of immune cell recruitment from the circulation into the peripheral nervous system in immune-mediated neuropathies. PMID- 8196364 TI - Correcting the PiZ defect in the alpha 1-antitrypsin gene of human cells by targeted homologous recombination. AB - BACKGROUND: Approximately 1% of people in North America carry the PiZ defect in the gene encoding the serum protein alpha 1-antitrypsin (AAT). Homozygotes are subject to early onset emphysema and liver disease. Here we demonstrate a means of correcting this gene defect, a point mutation in chromosome 14, by targeted homologous recombination. EXPERIMENTAL DESIGN: To target recombination to the AAT locus in human cells we use a normal complementary DNA cleaved once approximately 400 base pairs upstream of the PiZ mutation site in exon V. After transfection, targeting is monitored using a polymerase chain reaction assay devised to uniquely amplify successful homologous recombinants. RESULTS: When excercised on human PiZZ GM2522 fibroblasts, targeting replaces exon V of the endogenous gene, containing the PiZ mutation, with the exon V counterpart of a normal complementary DNA, simultaneously displacing the mutated exon V away from its promoter. By reversing the targeting strategy and using human PiM hepatoma cells, we have been able to supplant a normal copy of the AAT gene with a mutated PiZ version. This has allowed us to culture human HepG2 cells expressing the pathologic phenotype of the PiZ defect. Immunocytologic staining demonstrates the presence of inclusions in the liver cells due to aggregation of the PiZ isoform encoded by the recombined AAT gene under control of the endogenous gene promoter. CONCLUSIONS: (a) Targeting to the AAT locus is observed, using the methods we have developed, at rates that render feasible the selection of targeted cells and isolation of clones bearing a corrected AAT gene. (b) Correction of the exon V PiZ mutation alone, regardless of an accompanying exon III mutation, is sufficient to prevent aggregation of the PiZ protein in human liver cells. (c) Targeted homologous recombination offers advantages in potential gene therapy to correct AAT defects. PMID- 8196365 TI - Priming for the synthesis of 5-lipoxygenase products in human blood ex vivo by human granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha. AB - BACKGROUND: Previous studies reported the priming effects of granulocyte macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF alpha) on leukotriene synthesis by isolated polymorphonuclear leukocytes; however, little is known as of yet of these biologic effects of the two cytokines in a physiologic environment. EXPERIMENTAL DESIGN: In this study, we investigate the effects of GM-CSF and TNF alpha on the synthesis of 5-lipoxygenase (5-LO) products in heparinized blood stimulated ex vivo, using reverse phase high performance liquid chromatography analysis of deproteinized plasma samples. RESULTS: Stimulation of blood with f-Met-Leu-Phe resulted in the accumulation of up to 30 pmol of 5-LO products/ml of plasma. Preincubation of blood with 100 pM GM-CSF or 1.2 nM (200 units/ml) TNF alpha for 30 minutes at 37 degrees C before stimulation with f-Met-Leu-Phe resulted in a marked enhancement (> 5-fold) of the synthesis of leukotriene B4 and 5(S)-hydroxyeicosatetraenoic acid, which were formed in equivalent amounts. GM-CSF and TNF alpha priming activities were detectable at concentrations as low as 3 pM and 6 pM (1 unit/ml), respectively. The preincubation times required for optimal priming by GM-CSF and TNF alpha were different (40 and 10 minutes, respectively), and the effects of the two cytokines on leukotriene B4 and 5(S)-hydroxyeicosatetraenoic acid synthesis were additive, suggesting different priming mechanisms. The synthesis of 5-LO products in primed blood was also induced by platelet-activating factor, the complement fragment C5a, the particulate stimulus zymosan, and the ionophore A23187, but not by interleukin-8. Polymorphonuclear leukocytes and mononuclear cells accounted for 80% and 20% of the synthesis of 5-LO products, respectively. CONCLUSIONS: These data demonstrate that GM-CSF and TNF alpha exert very potent priming effects on the biosynthesis of 5-LO products in whole blood stimulated by various stimuli and strongly support that these cytokines could be important modulators of lipid mediator synthesis in physiologic and pathophysiologic conditions. PMID- 8196366 TI - Turnover of extracellular-superoxide dismutase in tissues. AB - BACKGROUND: The secretory glycoprotein, extracellular-superoxide dismutase (EC SOD) is in the body, primarily located to the tissue interstitial space, and in tissue is almost completely composed of homotetrameric high-heparin-affinity C type. The aim of the present study was to determine the turnover rate of EC-SOD C in tissue and the importance of the heparin-affinity for the retention. EXPERIMENTAL DESIGN: EC-SOD C and two EC-SOD carboxyterminal truncation variants with reduced and absent heparin-affinities, respectively, were labeled with 125I and then subcutaneously and intramuscularly injected into rats. The retentions were followed with repeated determinations with a gamma camera. RESULTS: EC-SOD C displayed a tissue half-life of about 85 hours, whereas the EC-SOD variants with reduced and absent heparin-affinities displayed half-lives of about 20 and 7 hours, respectively. The half-lives were remarkably similar in the intramuscular and subcutaneous injection sites, suggesting rather small overall differences between tissues in EC-SOD C retention. CONCLUSIONS: The findings established that EC-SOD C in the tissue interstitium exists almost completely anchored to heparan sulfate proteoglycan via the carboxyterminal heparin-binding domains, and that this binding is the determinant of the long tissue retention of the enzyme. The findings further suggest that reductions in heparin-affinity, e.g., by proteolytic truncation of the highly susceptible heparin-binding domain, may be an important mechanism of elimination of EC-SOD from tissues, both physiologically and as enhanced under pathologic conditions. PMID- 8196367 TI - Kinetic analysis of spongiform neurodegenerative disease induced by a highly virulent murine retrovirus. AB - BACKGROUND: A chimeric murine retrovirus, FrCasE, causes a rapid noninflammatory spongiform neurodegenerative disease of the motor system with an incubation period of 15 to 16 days after neonatal inoculation. Neurovirulence is determined by the viral envelope gene, but the neurodegeneration is an indirect consequence of virus infection, because the neurons that degenerate appear not to be infected. EXPERIMENTAL DESIGN: The current study was undertaken to compare the kinetics of lesion development and the expression of viral envelope protein in the central nervous system (CNS). Neonatal mice were inoculated with FrCasE intraperitoneally and were killed at various times for determination of the kinetics of the CNS infection, the distribution of lesion in the CNS, and the distribution of viral envelope protein. In addition, qualitative features of both viral envelope and gag proteins were followed by immunoblot analysis. RESULTS: The lesions induced by FrCasE consisted of vacuolar degeneration but without associated astrocytosis, the lack of an astroglial response being a consequence of the rapidity of the disease process. Vacuoles were observed primarily in the neuropil of the motor centers of spinal cord, brain stem, and cerebral cortex. Lesions appeared in all of these areas during a narrow window of time (< or = 3 days). Cells in which viral envelope protein was detected by immunohistochemistry before the appearance of spongiform degeneration included premigratory cerebellar cortical granule neurons as well as vascular elements in the regions that would ultimately exhibit spongiform degeneration. Two forms of viral envelope protein were detected in the CNS. A 70-kilodalton species appeared first, followed by an approximately 64-kilodalton species, which was detected coincident with the first appearance of spongiform lesions. CONCLUSIONS: Astrocytosis is a secondary reaction to the neuronal cytopathology induced by FrCasE and appears to be dependent on the developmental state of the CNS. The abrupt, diffuse nature of lesion development in this disease suggests a global effect of the virus infection. Cells of the CNS vasculature (either endothelial cells, perivascular microglial cells, or both) as well as cerebellar granule neurons appear to be seminally involved in the pathogenesis of the spongiform degeneration. The two species of viral envelope protein appear to be expressed by different cell types in the CNS. PMID- 8196368 TI - Differential expression of beta 1, beta 3, and beta 4 integrin subunits in nonneoplastic neural cells of the peripheral and autonomic nervous system and in tumors derived from these cells. AB - BACKGROUND: Extracellular matrix proteins and their receptors take part in physiologic neural development and organization and also in abnormal neoplastic growth and spread. There is increasing evidence for the implication of integrins in these processes. EXPERIMENTAL DESIGN: Human tissues containing nonneoplastic neural cells of the peripheral and autonomic nervous system and a comprehensive series of neural tumors were examined for the in situ expression of beta 1, beta 3, and beta 4 integrins. Serial frozen sections of each tissue sample were immunostained using an indirect streptavidin/biotin-peroxidase method and monoclonal antibodies against beta 1, alpha 1 to alpha 6, beta 3, alpha v, and beta 4 subunits. RESULTS: Both small- and large-diameter nerve fibers of normal peripheral nerve trunks were consistently beta 1+, alpha 6+, and beta 4+ in the absence of alpha 3, alpha 4, alpha 5, and beta 3. Small-diameter nerve fibers further expressed alpha 1, alpha 2, and alpha v. Meissner's corpuscles and inner cores of Pacinian corpuscles shared the integrin repertoire of small-diameter nerve fibers with additional expression of alpha 3; outer cores of Pacinian corpuscles were beta 1+, alpha 3+, alpha 6+, and beta 4+. Regenerating nerve fibers paralleled the integrin profile of normal peripheral nerves. By contrast, malignant schwannomas showed considerable changes in integrin expression. These alterations consisted mainly in a neoexpression of alpha 3, alpha 4, and alpha 5 and in an abnormal loss of alpha 6 and beta 4. Expression of alpha 1, alpha 2, and alpha v was variable; absence of beta 3 was generally conserved. In ganglion cells, integrin expression was restricted to beta 1 and alpha 3 subunits, and chromaffine cells of the adrenal medulla even lacked any detectable beta 1, beta 3, and beta 4 integrin subunits. (Ganglio)-neuroblastomas, however, were beta 1+, alpha 1+, and alpha 3+, whereas primitive peripheral neuroectodermal tumors were beta 1+ and alpha 5+. CONCLUSIONS: Nonneoplastic human neural cells exhibit a complex and, at the same time, differential pattern of beta 1, beta 3, and beta 4 integrin subunit expression. Malignant transformation leads to considerable changes in this integrin profile. The observation of neoplasia-associated abnormalities underlines the important role of integrins in the orderly development and maintenance of human neural tissue. Some aspects of the emerging integrin subunit patterns are useful for the differential diagnosis of neural soft-tissue tumors. PMID- 8196369 TI - Age-related changes in guinea pig prostatic stroma. AB - BACKGROUND: The histology of benign disease of the human prostate (benign prostatic hyperplasia) is heterogeneous. No other species demonstrates the same complexity, and current animal models do not appear to fully encompass the stromal and epithelial developmental changes involved in the human disease. This study describes age-related changes in the prostatic smooth muscle stroma of guinea pigs and humans, which may be pertinent to some aspects of the disease process in humans. EXPERIMENTAL DESIGN: Histologic and ultrastructural changes were examined and measured in the prostates of guinea pigs during aging (2 weeks to 31 months). Similar measurements were also made in human prostatic tissues during aging and the development of benign prostatic pathology. RESULTS: Morphometric analyses of prostates in guinea pigs and men demonstrated similar changes in stromal volume with age. The stromal volume proportion of the prostate in both species decreases at puberty due to the expansion of the epithelial cell compartment, and is followed by a progressive increase during adulthood until a maximum stromal content of approximately 75% of total tissue volume is reached at age 2 years in guinea pigs, and at age 70 years in men. The pathognomic feature of nodularity and the dramatic increase in gland size observed during the late stages of human benign prostatic disease did not occur in the guinea pig prostate. Ultrastructural analysis of guinea pig prostatic smooth muscle cells identified a progressive hypertrophy (approximately 10-fold) from prepuberty through to old age. Two-thirds of smooth muscle cells in the prostatic stroma of aging individuals of both species demonstrated perinuclear organelles (rough endoplasmic reticulum and free ribosomes) that were not present in younger individuals. CONCLUSIONS: The prominent histologic features of the guinea pig prostate during aging are increased stromal mass, significant stromal fibrosis, and occasional prostatitis. These features are frequently observed in men with clinical benign prostatic hyperplasia. The age-related increases in prostatic smooth muscle cell size and content of perinuclear organelles in the guinea pig suggest a re-activation of cellular synthetic activity. The similarity in some features of the prostatic smooth muscle stroma between aging men and guinea pigs suggests that there may be common pathophysiologic processes. We conclude that the guinea pig could be a useful model for examination of the age-related hypertrophy of the smooth muscle cell and the processes inducing reversion to a more synthetic smooth muscle cell phenotype. PMID- 8196370 TI - Aging diminishes gastric mucosal regeneration: relationship to tyrosine kinases. AB - BACKGROUND: Increased incidence of gastric ulcer observed in the aged could be partly attributed to increased susceptibility of the mucosa to various damaging agents together with impediment of the repair process. The present investigation was undertaken to compare the rate of mucosal regeneration and the role of tyrosine kinases in regulation of this process between young (4-month-old) and aged (24-month-old) rats during the first 24 hours after injury. EXPERIMENTAL DESIGN: Groups of young and aged rats were given intragastrically with either 2 M NaCl (1.5 ml/130 gm body weight), or an equivalent volume of water and killed 1, 6, and 24 hours later. Each animal was injected intraperitoneally with 5-bromo-2' deoxyuridine (BrdU; 50 mg/kg) 1 hour before killing to assess proliferative activity by immunocytochemistry. The stomach (oxyntic gland area) was also evaluated by light microscopy for the extent of injury and subsequent regeneration, and mucosa assayed for ornithine decarboxylase and tyrosine kinase (Tyr-k) activity and tyrosine phosphorylation of membrane proteins. RESULTS: Although 2 M NaCl caused extensive damage to the gastric mucosa in both young and aged rats, as evidenced by the total loss of the surface epithelium at 1 hour postinjury, the degree of regeneration was faster in young animals. In young rats, gastric epithelium showed signs of regeneration at 6 hours postinjury and was essentially complete by 24 hours. In contrast, in aged rats, only intermittent surface cells were seen 24 hours after injury. In both age groups, injury resulted in stimulation of mucosal proliferative activity. However, whereas ornithine decarboxylase activity in both age groups was maximally stimulated (350% in young versus 80% in aged) at 6 hours after injury, the number of BrdU-positive cells in young rats increased steadily with time after injury. In contrast, aged rats showed a biphasic pattern in that the number of BrdU positive cells/gland remained decreased for up to 6 hours, whereafter a steep rise occurred. At 24 hours after injury, the number of BrdU-positive cells/gastric gland in aged rats were found to be higher than in young rats (6 +/ 1.5 cells/gland in young rats versus 9 +/- 2.1 cells/gland in aged rats). The pattern of Tyr-k activity in young and aged rats after injury was found to be quite different from that observed for proliferative activity. In young rats, mucosal Tyr-k activity increased by about 60% at 1 hour after injury, then decreased slightly over the next 5 hours and increased again revealing a 120% rise at 24 hours postinjury. This was associated with a concomitant change in tyrosine phosphorylation of six membrane proteins with molecular weight (in kilodalton) of 30, 35, 50, 55, 60 and 70. In contrast, in aged rats, Tyr-k activity was increased only marginally (about 20%) during the first 6 hours, but at 24 hours postinjury it was found to be 70% above the control. In aged rats, injury produced no significant stimulation in tyrosine phosphorylation of gastric mucosal membrane proteins. CONCLUSIONS: We conclude that aging is associated with the diminished regenerative capacity of the gastric mucosa. This could partly be attributed to diminished activation of mucosal Tyr-k and decreased tyrosine phosphorylation of certain membrane proteins. PMID- 8196371 TI - Simultaneous detection of messenger ribonucleic acids for bombesin/gastrin releasing peptide and its receptor in rat brain by nonradiolabeled double in situ hybridization. AB - BACKGROUND: To simultaneously detect gene expression for bombesin/gastrin releasing peptide (GRP) and its receptor in routinely processed tissue sections, we developed a protocol for non-radioactive double in situ hybridization (ISH) method. EXPERIMENTAL DESIGN: We used digoxigenin-labeled cRNA probe for GRP and a biotinylated cRNA probe for GRP-receptor (GRP-R) on frozen and/or formalin-fixed, paraffin-embedded sections of rat brain. The probes were applied singly and mixed (double ISH) and the signals visualized with two distinct chromogens. Antidigoxigenin-alkaline-phosphatase conjugate and nitro blue tetrazolium, producing a blue color reaction, was used to visualize GRP mRNA, and for GRP-R mRNA, avidin-alkaline phosphatase and vector red, were used resulting in a vivid red color. To unmask the signals on formalin-fixed, paraffin-embedded tissue, the sections were pretreated with proteinase VIII. RESULTS: Strong specific signals for GRP and/or GRP-R were detected in rat-brain neurons. The localization and intensity of the signal was comparable on frozen and routinely processed sections, although the latter showed better cytology and resolution. The overall distribution of GRP and GRP-R mRNAs in rat brain was similar to that previously reported with single ISH using radioactive-labeled probes. Double ISH revealed colocalization of the two mRNAs in some neurons with the expression of GRP mRNA often coexpressed with GRP-R mRNA. However, the expression of GRP-R mRNA did not always correlate with GRP mRNA signal. CONCLUSIONS: The nonradioactive, double ISH method is a relatively simple and sensitive procedure applicable to routinely processed tissues. This method may be suitable for studies on temporal and spacial distribution of peptide(s) and peptide receptor gene expression in health and disease. PMID- 8196372 TI - Principals' and teachers' views of sexuality education in Flanders. AB - This survey was part of the first systematic large-scale assessment on the practice of sexuality education in Flanders. A representative sample of 400 secondary schools was drawn from a total of 1,050 schools. A positive view toward school-based sexuality education was found for both school principals and teachers. However, time devoted to sexuality education is too restricted, and teaching strategies are too verbal to expect changes in attitude and behavior with regard to contraception and AIDS prevention. Next to the low popularity of active teaching methods, ignorance of the discrepancy between goals set and methods used, and the low value attached to improving the skills of students in using contraceptives, were critical findings. Rather than increasing instruction time, discussion of the relationship among goals, methods, and training in the use of active methods would be more beneficial to improving sexuality education in Flanders. PMID- 8196373 TI - Inflight decisions of expert and novice health teachers. AB - The interactive or "inflight" decision-making of nine expert health teachers and 10 student health teachers was examined over a two-year period. The method for accessing thoughts of the teachers was the stimulated recall interview which first involved making a videotape of the lesson being taught. After the lesson, the researcher played the videotape and the teachers stopped the tape whenever they could recall what they were thinking at the time. Each interview was audiotaped and responses served as data for this study. Overall, expert health teachers made more interactive decisions in the classroom across a larger number of categories. Specifically, experts remembered making significantly more decisions in the five categories of pupil, content, procedures, time, and materials. Expert health teachers also were generally more cognizant of lesson objectives, more likely to modify the lesson, and better able to connect new material to students' prior learning. Recommendations for preservice and inservice professional development programs are offered. PMID- 8196374 TI - Are local teachers or nutrition experts perceived as more effective among Brazilian high school students? AB - A preliminary experimental study was conducted among 322 high school students in the Amazon region of Brazil to determine whether locally-trained teachers (high similarity/low expertise) or outside nutrition experts (high expertise/low similarity) would more effectively influence food choice attitudes and behavior. Subjects were randomly assigned to a control group or one of four treatment groups in which participants read a nutrition message and one of four accompanying author descriptions (high communicator similarity/high expertise, high similarity/low expertise, low similarity/high expertise, low similarity/low expertise). Subjects then responded to food choice attitude and behavior scale items. ANOVAs revealed only perceived similarity significantly influenced attitude and behavior. Thus, training local Brazilian nutrition educators perceived to be highly similar to Brazilian adolescents may be more cost effective than recruiting nutrition experts. This study's consistency with studies conducted among Kenyan and American adolescents suggests perceived communicator similarity is a critical factor in international adolescent nutrition education. PMID- 8196375 TI - Preparing school personnel to assist students with life-threatening food allergies. PMID- 8196376 TI - The hepatitis B occupational risk worksheet. PMID- 8196377 TI - Applying cooperative learning in health education practice. AB - Cooperative learning encompasses both a teaching philosophy and instructional methods that encourage students to work together to maximize learning. This article examines the rationale for incorporating cooperative learning in health education, reviews cooperative learning basics, and provides an example of cooperative learning technique in health education. PMID- 8196378 TI - High-dose irradiation prevents rejection of canine tracheal allografts. AB - We investigated the possibility of immunosuppressant-free transplantation of the trachea using high doses of 60Co gamma irradiation of the graft before transplantation. Twenty mongrel dogs were used. Five rings of the trachea were removed from the donors and irradiated with 60Co gamma rays. Five corresponding rings were removed from the thoracic trachea of the recipient dogs, and the irradiated trachea was transplanted. Five animals were placed in each of four dosage groups: group A, no irradiation; group B, 20,000 cGy; group C, 50,000 cGy; and group D, 100,000 cGy. The anastomotic site and graft were covered with a pedicled greater omentum graft. No immunosuppressants were given. In group A, all the animals died within 1 month of tracheal stenosis caused by graft rejection. In groups B and C, one animal in each group survived for a long period, but all the others died of tracheal stenosis caused by graft rejection. In group D (100,000 cGy), the graft became incorporated into the recipient tissue in four of the five animals, and three are still alive (more than 1 year later). These findings indicate that allotransplantation of the trachea without the use of immunosuppressants is possible with pretransplantation irradiation of the graft at the dose of 100,000 cGy. PMID- 8196379 TI - Surgical results and prognostic factors of pathologic N1 disease in non-small cell carcinoma of the lung. Significance of N1 level: lobar or hilar nodes. AB - The surgical outcome of pathologic N1 disease is controversial. To clarify whether pathologic N1 disease is a uniformly intermediate group or a mixed group of potentially early stage disease and advanced stage disease, we reviewed our previous cases with pathologic N1 disease. We retrospectively investigated 78 patients with pathologic N1 disease who had undergone a complete resection with mediastinal lymph node dissection during the period from April 1972 to December 1990. The cumulative postoperative survival at 5 years was 49.2%. No significant difference in the survival was found according to the following variables: sex, primary site, pathologic T factor, histologic type, type of resection, performance of adjuvant therapy. The lobar lymph nodes (Nos. 12 and 13) were only involved in 30 patients (38.5%), whereas the hilar nodes (Nos. 10 and 11) were involved in 48 patients (61.5%). The survival associated with lobar N1 disease was significantly better than that of hilar N1 disease (64.5% versus 39.7% at 5 years; p = 0.014). In lobar N1 disease, the brain was the most frequent site of distant metastasis, whereas the lungs were the most frequent site in hilar N1 disease. It was suggested that pathologic N1 disease is a mixed group of potentially early stage disease and advanced stage disease with regard to the postoperative prognosis. PMID- 8196380 TI - Exercise cardiorespiratory function before and one year after operation for pectus excavatum. AB - In 35 patients with pectus excavatum (aged 17.9 +/- 5.6 years) pulmonary function and maximal exercise test results were compared before and at 1 year after operation. The lower posteroanterior chest diameter on the lateral x-ray film was significantly smaller than normal (p < 0.0001) and increased significantly after operation (p < 0.0001). Preoperatively, total lung capacity (86.0% +/- 14.4%; p = 0.0001) and inspiratory vital capacity (79.7% +/- 16.2; p = 0.0001) were significantly smaller than predicted and further decreased after operation (-9.2% +/- 9.2%; p = 0.0001 and -6.6% +/- 10.7%; p = 0.0012, respectively). Arterial blood gas values displayed normal patterns with increasing exercise both before and after operation. Only the arterial pH decreased more after operation than before (p = 0.0026). After operation there was a significant increase in maximal oxygen uptake (oxygen uptake; p = 0.0002 and oxygen uptake per kilogram; p = 0.0025) and oxygen pulse (oxygen uptake/heart rate approximates an indirect parameter for stroke volume; p = 0.0333) during exercise, whereas the maximal work performed was unchanged. Efficiency of breathing (ratio of tidal volume/inspiratory vital capacity) at maximal exercise improved significantly after operation (p = 0.0005). Ventilatory limitation of exercise (defined by an increase in carbon dioxide tension during exercise) was found in 43.9% of the patients before operation. A tendency of improvement was noted (not significant) after operation (difference in carbon dioxide tension 0.6 +/- 0.4 kPa before versus 0.3 +/- 0.5 kPa after operation). However, the group with normal preoperative carbon dioxide elimination had a ventilatory limitation of exercise after operation (difference in carbon dioxide tension -0.4 +/- 0.3 kPa before versus -0.1 +/- 0.3 kPa after operation; p = 0.0128) with a significant increase in oxygen consumption (p = 0.0007). In conclusion the subjective physical improvement after operation is not explained by changes in cardiorespiratory function at exercise. The data suggest a higher work of breathing after operation. PMID- 8196381 TI - Three years' experience in video-assisted thoracic surgery (VATS) for spontaneous pneumothorax. AB - In a prospective study (June 1990 to June 1993), 79 patients were treated for spontaneous pneumothorax by video-assisted thoracoscopic methods with regular follow-up. The observation time was from 3 to 36 months (mean 19.6 months) and was more than 24 months in 27 patients. In 57 patients spontaneous pneumothorax was primary and in 22 secondary. The 53 male and 26 female patients were aged between 17 and 87 years (mean 37 years). Twenty-one patients were treated thoracoscopically for first episode, 22 for persistent pneumothorax (> 7 days), and 36 for a recurrence. Endoscopic examination failed to reveal any lung alteration in four patients (5.1%), and treatment then consisted of simple drainage. Leaks were sealed 26 times by means of a Roeder loop with local anesthesia and 14 times by wedge resection with endotracheal anesthesia and one lung ventilation; 34 patients were treated by pleurectomy. No deaths occurred. Surgical morbidity was 3.8%, and the postoperative complication rate was 5.1%. One patient was excluded from the follow-up study after conversion to a thoracotomy for control of arterial bleeding. We noted six recurrences; four occurred in the first 21 days and three after ligation of the leak with a Roeder loop. We conclude that video-assisted thoracoscopic treatment of spontaneous pneumothorax by wedge resection and pleurectomy has a recurrence-free rate of 93.8% (45/48) and is therefore an effective treatment for all forms of spontaneous pneumothorax. PMID- 8196382 TI - Inhibition of the fetal stress response improves cardiac output and gas exchange after fetal cardiac bypass. AB - Cardiac bypass in late-gestation fetal lambs causes severe placental vasoconstriction, which leads to fetal death from hypoxemia and respiratory acidosis. This response can be blocked by the administration of indomethacin; however, a fatal metabolic acidosis then gradually develops in the fetus. Because the fetus is known to mount an intensive catecholamine response to stress, and because the fetal myocardium is particularly sensitive to increased afterload, we hypothesized that elevated afterload as a result of fetal stress contributes to diminished cardiac output after bypass. Twenty fetal lambs at 80% gestation underwent 30 minutes of normothermic cardiac bypass at flow rates of 200 to 500 ml/kg per minute. All ewes received general anesthesia with ketamine. In 10 fetuses general anesthesia was specifically designed not to inhibit the release of stress-related catechols (ketamine); the remaining 10 fetuses received a "high" (cisterna magna) total spinal anesthetic with tetracaine, to block the fetal stress response. In each anesthetic group, 5 of the 10 lambs received indomethacin. During operation, normal hemodynamics were preserved in the spinal anesthetic group. Cardiac output, placental blood flow, and arterial carbon dioxide tension were all improved relative to results in the ketamine group. When spinal anesthesia and indomethacin are both given, hemodynamics also approach normal after bypass, and gas exchange is further improved. These data suggest that the inhibition of the stress response by spinal anesthesia improves the hemodynamic status of the fetus during operation and, in combination with indomethacin, allows maintenance of near-normal placental function after fetal cardiac bypass. Similar responses may also be possible in human fetuses with use of a high-dose narcotic technique. PMID- 8196383 TI - Long-term survivors of fetal cardiac bypass in lambs. AB - The initial experience with cardiac bypass in fetal lambs resulted in early fetal death from placental insufficiency. Subsequent work in our laboratory indicated that vasoactive cyclooxygenase products were released as mediators of this response. The placental dysfunction could be blocked by the administration of indomethacin, allowing longer fetal survival. This unmasked a more subacute (but fatal) problem: fetal surgical stress resulted in diminished fetal cardiac output and progressive metabolic acidosis and contributed to the placental vasoconstriction. In acute studies, when indomethacin was given and the stress response was inhibited by the use of total spinal anesthesia, the fetus maintained normal blood gas levels, cardiac output, placental blood flow, and acid-base status for several hours after bypass. We hypothesized that beyond this point, no further fetal or placental compromise would occur and that this management technique would thus allow long-term fetal survival. With the use of total spinal anesthesia and sterile technique for long-term study, 12 fetal lambs at 120 days (80%) gestation underwent exposure, line placement, and cannulation for fetal cardiac bypass. Indomethacin was given intravenously on obtaining venous access. After 20 minutes of normothermic cardiac bypass at flow rates of 250 to 300 ml/kg/min, the fetus was weaned from bypass, the cannulas and lines were removed, the uterus and abdomen were closed, and the ewe and fetus were allowed to recover. There was one maternal death (pneumonia) and one early abortion (of twins); the remaining 10 ewes progressed to term. At term, five healthy lambs that had undergone fetal cardiac bypass were delivered (including one twin), four ewes delivered a mummified study fetus and one or two healthy siblings, and one delivered a dead term fetus. With the use of techniques that inhibit fetal stress and block placental vasoconstriction, cardiac bypass can be performed in single-gestation fetal lambs with a high degree of recovery and survival (80% in this study). The cause of the elevated abortion rate associated with twin gestation is unclear. PMID- 8196385 TI - Pharmacologic dilatation of the internal mammary artery during coronary bypass grafting. AB - Spasm of the internal mammary artery during coronary bypass grafting is a widely recognized problem during and after mobilization of the IMA. On the basis of previous laboratory studies, we have developed a buffered vasodilator solution containing glyceryl trinitrate and verapamil (pH 7.4). When tested in human internal mammary artery segments in the organ bath, this solution caused full relaxation of the segments with a 1- to 2-minute onset and a duration of action of more than 2 hours. In 31 patients undergoing internal mammary artery grafting, flow through the internal mammary artery was measured immediately after mobilization and 20 minutes later. In 10 untreated patients, flow increased by 13% from 41.8 +/- 7.1 to 47.3 +/- 7.5 ml/min (p < 0.025). In 11 patients, intraluminal injection of glyceryl trinitrate-verapamil solution into the internal mammary artery on one side caused an increase in flow of 55 +/- 10 ml/min (95%), which was greater than that caused by Ringer's solution, 22 +/- 8 ml/min (53%), in the opposite internal mammary artery (p < 0.025). In another 10 patients intraluminal injection of glyceryl trinitrate-verapamil solution in one internal mammary artery caused an increase in flow of 57.9 +/- 8.7 ml/min (107%), which was similar to that caused by papaverine solution (pH 5.2) in the opposite internal mammary artery of 45.0 +/- 12.3 ml/min (80%). We conclude that intraluminal injection of vasodilator solution is effective in dilating the IMA graft and that because of its rapid onset, long action, and neutral pH, glyceryl trinitrate-verapamil solution may be preferable to papaverine. PMID- 8196384 TI - Total circular annuloplasty with absorbable suture for the repair of left atrioventricular valve regurgitation in atrioventricular septal defect. AB - To obtain a better control of left atrioventricular valve regurgitation, we applied total circular annuloplasty with the use of absorbable sutures to 14 children with atrioventricular septal defect (six complete forms and eight incomplete forms). In the intraoperative period, a good coaptation of the leaflets was achieved and the regurgitation was minimized or disappeared. Follow up studies with echocardiography for 13 survivors showed a gradual increase of annular size during the postoperative period. Ten patients of the survivor group (77%) maintained good valvular competency in a long-term period. Total circular annuloplasty is a simple and effective procedure to reduce the regurgitation and prevent the annular dilatation during the immediate postoperative period. PMID- 8196386 TI - Comparison of saphenous vein graft relaxation between Plasma-Lyte solution and normal saline solution. AB - Venospasm of saphenous vein grafts may damage endothelial cells and compromise early and late graft performance. Hence it is desirable to identify and use storage solutions that minimize vascular spasm during vein preparation. In view of this, we initiated isometric tension-recording studies in isolated canine and human saphenous vein to evaluate the acute, vasoactive effects of two storage solutions, Plasma-Lyte solution and normal saline solution. In initial experiments, canine saphenous veins were mounted in tissue baths containing physiologic salt solution and tonically constricted by 2 x 10(-6) mol/L norepinephrine. The physiologic salt solution in the bath was then replaced by Plasma-Lyte solution or normal saline solution containing the same norepinephrine concentration, and changes in contraction amplitude were recorded for 90 minutes. Storage in Plasma-Lyte solution at 37 degrees C completely relaxed norepinephrine activated canine saphenous vein within 20 minutes, whereas veins remained partially constricted in normal saline solution. Both Plasma-Lyte solution and normal saline solution relaxed canine saphenous vein less at room temperature (25 degrees C) than at 37 degrees C, implying that warming of storage solutions in the operating room may promote graft dilation. To identify the mechanism by which Plasma-Lyte solution induced relaxation, we replaced its putative vasodilator components of gluconate and acetate with NaCl, but this alteration did not reduce relaxation induced by Plasma-Lyte solution. However, adding 1.6 mmol/L CaCl2 to Plasma-Lyte solution completely reversed the venodilation, suggesting that the low Ca2+ content of Plasma-Lyte solution confers its relaxant action. Finally, we tested the vasoactive effect of Plasma-Lyte solution on human saphenous vein obtained by discard from coronary bypass operations. Plasma-Lyte solution at 37 degrees C effectively dilated norepinephrine-activated human saphenous vein, inducing complete relaxation within 20 minutes. On this basis, we recommend the use of Plasma-Lyte solution as a venodilating storage solution during coronary bypass operations to optimize vein graft relaxation before implantation. PMID- 8196388 TI - Management of persistent tricuspid endocarditis with transplantation of cryopreserved mitral homografts. AB - Transplantation of the human mitral valve in the tricuspid position for intractable infective endocarditis has been successfully performed in three young patients who were addicted to drugs. The maximum follow-up is 20 months. The rationale and historical basis for using this approach in the surgical treatment of patients with right-sided infective endocarditis is discussed and the appropriate literature reviewed. Because the technical aspects have been previously reported, this article can be considered an argument to renew past interest in atrioventricular valve replacement with fully biologic tissue of human origin. PMID- 8196387 TI - Surgical revascularization after fibrinolysis in acute myocardial infarction. Long-term follow-up. AB - One hundred twenty-eight patients with myocardial infarction who underwent operation for myocardial revascularization and 147 patients who received medical therapy were followed up for up to 6 years: all patients had received treatment with intravenous streptokinase. In the surgical group, 91.5% of the patients had the region related to the infarction revascularized, and in 82.8% of them the mammary artery was used. Statistically significant differences were not detected between the groups according to infarct size, clinical features, and left ventricular ejection fraction. However, there was a higher risk in the surgical group, as compared with that in the medical group, in terms of anatomic characteristics: 99.2% versus 77.1% of the patients showed more than 70% residual obstruction at the "culprit" coronary artery (p < 0.001, 95% confidence interval 14.1% to 30.1%) and 76.8% versus 40.7% showed multivessel coronary disease (p < 0.001, 95% confidence interval 23.7% to 48.5%). In-hospital survival was 95.3% in the surgical group and 89.1% in the medical group (p = 0.096, 95% confidence interval -0.2% to 12.6%). Significantly higher survivals were obtained for the surgical group both during the first (93% +/- 2.3% versus 80.3% +/- 3.3%, p = 0.005) and the sixth (86.4% +/- 3.4% versus 68.4% +/- 4.3%, p = 0.003) year of follow-up. Statistically significant differences were also obtained when in hospital deaths were excluded. A Cox regression model with 13 variables showed that only age (p = 0.0422) and medical treatment (p = 0.0194) correlated independently with mortality. It is concluded that in this nonrandomized study, operation led to a significantly higher survival both on a medium- and long-term basis, when compared with that obtained for patients receiving medical therapy. PMID- 8196389 TI - Transaortic repair of ruptured aneurysm of sinus of Valsalva. Fifteen-year experience. AB - Between 1978 and 1993 a total of 25 cases of ruptured aneurysm of the sinus of Valsalva underwent transaortic repair at the Railway Hospital and the Institute of Cardiovascular Diseases at Madras, India. The aneurysms ruptured into the right ventricle in 20 patients, into the right atrium in 2, into the left ventricle in 1, and into the interventricular septum in 2. They originated from the right coronary sinus in 22 patients and from the noncoronary sinus in 3. Associated congenital anomalies included ventricular septal defect in 21, tetralogy of Fallot in 1, and pulmonary stenosis in 1. All 25 patients underwent transaortic repair of the ruptured sinus of Valsalva, and in patients with a ventricular septal defect the defect also was closed via this route. The patient with associated pulmonary stenosis had a pulmonary valvotomy. The patient with tetralogy of Fallot had infundibular resection, ventricular septal defect closure via a transatrial route, and a right ventricular outflow patch. No intraoperative deaths occurred, but one early death resulted from septicemia and multiorgan failure after rupture of the aneurysm into the interventricular septum with consequent development of extensive intramyocardial and epicardial abscesses. One late death occurred as a result of recurrent subacute bacterial endocarditis and septicemia. Transaortic repair of ruptured aneurysm of the sinus of Valsalva can be accomplished with a low risk of mortality and has the advantage that an associated ventricular septal defect, which frequently accompanies this condition, can be conveniently closed via the same route. PMID- 8196390 TI - Surgical management of aneurysms at the origin of an aberrant right subclavian artery. AB - An aneurysmal origin of an aberrant right subclavian artery should preferably be closed with a prosthetic patch inserted with the aid of cardiopulmonary bypass with deep hypothermia and circulatory arrest. Three patients were operated on: a transaortic approach was used in two and a transaneurysmal approach in one. This technique allows a single-stage surgical correction of this rare anomaly through a median sternotomy and obviates the need for hazardous and difficult side clamping of the aorta. PMID- 8196391 TI - Histocompatibility differences and cardiac transplant tolerance produced by intrathymic pretreatment. AB - Control of cardiac transplant rejection without toxic immunosuppressive drugs remains an unreached goal. Our laboratory and others have shown that intrathymic inoculation of donor-specific allogeneic spleen cells can produce tolerance to a subsequent cardiac allograft. The present experiments were designed to investigate whether the degree of donor-recipient histoincompatibility influenced the efficacy of this technique. Four congeneic strains of rats with different degrees of histoincompatibility were studied. Heterotopic cardiac transplantation was done with the following congeneic strain combinations: DA donor into PVG recipient (full major histocompatibility complex and nonmajor histocompatibility complex incompatibility); PVG.RT1a donor into PVG recipient (full major histocompatibility complex incompatibility); PVG.RT1a donor into PVG.R1 recipient (partial major histocompatibility complex incompatibility). Prospective graft recipients underwent intraperitoneal injection of 1 ml antilymphocyte serum and intrathymic injection of 5 x 10(7) prospective donor spleen cells. Three weeks later, heterotopic cardiac transplantation was done with a heart from a donor of the same strain as that used to obtain splenocytes for intrathymic injection. Prolongation of graft survival was observed in pretreated recipients in all strain combinations but was greatest in recipients that differed from donors at fewer histocompatibility loci. Complete graft tolerance was not seen in strain combinations that included nonmajor histocompatibility complex incompatibilities. DA heart survival in PVG recipients was 50.6 days (p < 0.04 versus controls); PVG.RT1a graft survival in PVG hosts was 165.8 days (p < 0.02 versus control) and in PVG.R1 recipients 163.8 days (p < 0.02 versus controls) with four of five grafts in each group surviving indefinitely (more than 200 days). PMID- 8196392 TI - Surgical treatment of airway complications after lung transplantation. AB - The treatment of dehiscence or stenosis of the bronchus after lung transplantation has to date consisted of endobronchial stenting or balloon dilation. Operative intervention has been limited to retransplantation with all its limitations. In our series of 121 anastomoses at risk, severe bronchial stenosis occurred in 11 (9%). In five instances the airway complications were treated surgically: two patients underwent retransplantation, one patient had a bilobectomy, and two required sleeve resection of the stenotic segment. All these procedures successfully removed the stenosis. This experience demonstrates that options other than bronchial anastomotic stenting and dilation may be successfully used to overcome posttransplantation anastomotic complications. Conventional resections may result in superior long-term graft function compared with retransplantation, avoiding the immunologically adverse effects of the latter procedure. PMID- 8196393 TI - Prevention of postoperative pericardial adhesions with a hyaluronic acid coating solution. Experimental safety and efficacy studies. AB - Postoperative pericardial adhesions complicate reoperative cardiac procedures. Topical application of solutions containing hyaluronic acid have been shown to reduce adhesions after abdominal and orthopedic surgery. The mechanism by which hyaluronic acid solutions prevent adhesion formation is unknown but may be due to a cytoprotective effect on mesothelial surfaces, which would limit intraoperative injury. In this study, we tested the efficacy and safety of hyaluronic acid coating solutions for the prevention of postoperative intrapericardial adhesion formation. Eighteen mongrel dogs underwent median sternotomy and pericardiotomy followed by a standardized 2-hour protocol of forced warm air desiccation and abrasion of the pericardial and epicardial surfaces. Group 1 (n = 6) served as untreated control animals. Group 2 (n = 6) received topical administration of 0.4% hyaluronic acid in phosphate-buffered saline solution at the time of pericardiotomy, at 20-minute intervals during the desiccation/abrasion protocol, and at pericardial closure. The total test dose was less than 1% of the circulating blood volume. Group 3 (n = 6) served as a vehicle control, receiving phosphate-buffered saline solution as a topical agent in a fashion identical to that used in group 2. At resternotomy 8 weeks after the initial operation, the intrapericardial adhesions were graded on a 0 to 4 severity scale at seven different areas covering the ventricular, atrial, and great vessel surfaces. In both the untreated control (group 1, mean score 3.2 +/- 0.4) and vehicle control (group 3, mean score 3.3 +/- 0.2) animals, dense adhesions were encountered. In contrast, animals treated with the hyaluronic acid solution (group 2, mean score 0.8 +/- 0.3) characteristically had no adhesions or filmy, transparent adhesions graded significantly less severe than either the untreated control (group 2 versus group 1, p < 0.001) or vehicle control (group 2 versus group 3, p < 0.001) animals. In separate experiments, six baboons were infused with 0.4% hyaluronic acid in phosphate-buffered saline solution in volumes equivalent to 2.5%, 5%, and 10% of the measured circulating blood volume. The 2.5% and 5% infusions had no effect on the parameters measured; infusion of the 10% volume produced transient hemodynamic, coagulation, and gas exchange abnormalities. Hyaluronic acid solutions are efficacious in the prevention of pericardial adhesions in this model, and they appear safe in doses five times the amount needed to prevent adhesions. Further studies investigating the mechanism by which these solutions prevent adhesions, their optimal dose and method of application, and documentation of their safe use in humans are warranted. PMID- 8196394 TI - Acute renal failure in the patient undergoing cardiac operation. Prevalence, mortality rate, and main risk factors. AB - A total of 775 consecutive patients who survived the first 24 hours after cardiac operation were prospectively studied to assess the prevalence, mortality rate, and main risk factors for development of new acute renal failure. Normal renal function before operation (serum creatinine level less than 1.5 mg/dl) was registered in 734 (94.7%) patients. Of these, 111 (15.1%) showed a postoperative renal complication including 84 (11.4%) classified as renal dysfunction (serum creatinine level between 1.5 and 2.5 mg/dl) and 27 (3.7%) as acute renal failure (serum creatinine level higher than 2.5 mg/dl). The mortality rate was 0.8% in normal patients, 9.5% in patients with renal dysfunction, and 44.4% when acute renal failure developed (p < 0.0001). Indeed, the renal impairment proved to be an independent predictor of mortality (p < 0.001), along with the infective (p < 0.001), gastrointestinal (p < 0.001), and cardiovascular (p < 0.05) complications. Multivariate analysis identified the following variables as independent risk factors for postoperative renal impairment: use of intraaortic balloon pump (p < 0.0001), need for deep hypothermic circulatory arrest (p < 0.005), low-output syndrome (p < 0.005), advanced age (p < 0.005), need for emergency operation (p < 0.025), and low urinary output during cardiopulmonary bypass (p < 0.05). The 41 patients (5.3%) with preoperative renal failure showed a significantly higher morbidity and mortality rate than those without renal complications before operation. We conclude that in patients undergoing cardiac operation without preexisting renal dysfunction the likelihood of severe renal complications is reasonably low, but the associated mortality remains high. A prominent role in the development of postoperative acute renal failure must be recognized for preoperative, intraoperative, and postoperative hemodynamic factors, whereas cardiopulmonary bypass seems to be of lesser importance in this respect. PMID- 8196395 TI - Left-to-right ventricular interaction with a noncontracting right ventricle. AB - Left ventricular systole is known to contribute to generation of right ventricular pressure and stroke volume. To study the interactions in a dilated noncontractile right ventricle after cardiopulmonary bypass we created a variable volume, neo-right ventricle by excision and replacement of the right ventricular free wall with a xenograft pericardial patch. We investigated the interactions in eight dogs with neo-right ventricle, instrumented to measure cardiac pressures and cardiac output in control conditions (n = 69) and during partial pulmonary artery occlusion (n = 50). RESULTS: The size of the neo-right ventricle was increased from original right ventricular volume V0 to V1 (V1 = V0 + 54 +/- 23 ml), V2 (V2 = V0 + 124 +/- 85 ml), and V3 (V3 = V0 + 223 +/- 162 ml). Cardiac output increased with increasing left ventricular end-diastolic pressure, indicating that the Frank-Starling mechanism was operating in the left ventricle. However, cardiac output decreased with increasing neo-right ventricular size (p < 0.001) and during pulmonary artery occlusion (p < 0.001). Maximal neo-right ventricular pressure was a linear function of the maximal left ventricular pressure at each neo-right ventricular size and decreased with the increase in neo-right ventricular size (p < 0.001), both in control conditions and during pulmonary artery occlusion (p < 0.004). Stroke work of the neo-right ventricle and left ventricle decreased with increasing neo-right ventricular size (p < 0.002). The relationship between neo-right ventricular stroke work and left ventricular stroke work at different neo-right ventricular sizes was linear both in control conditions and during pulmonary artery occlusion: in control Y = 0.24X (r = 0.968, n = 69); in pulmonary artery occlusion Y = 0.35X (r = 0.986, n = 50). In both conditions the intercept of the linear relationship was not significantly different from zero (p < 0.974 in control; p < 0.614 in pulmonary artery occlusion). The slope was significantly increased in pulmonary artery occlusion (p < 0.001). CONCLUSION: Left ventricular contraction contributes 24% of left ventricular stroke work to the generation of right ventricular stroke work via the septum in the absence of a contracting right ventricle; this increases to 35% in the face of increased pulmonary afterload. This mechanism can maintain adequate global cardiac function in the case of a noncontracting right ventricle while right ventricular volume is kept small and afterload is not increased. The interventricular interaction of the ventricles must be considered when patients with postbypass right ventricular failure are treated. PMID- 8196396 TI - Left ventricular mechanics during synchronous left atrial-aortic bypass. AB - The purpose of this study was to analyze left ventricular mechanics during asynchronous, pulsatile left atrial-aortic bypass before and after microsphere injection with the pressure-volume relationship. In 14 anesthetized Holstein calves, left ventricular pressure was measured with a micromanometer and ultrasonic dimension transducers measured left ventricular orthogonal diameters. Ellipsoidal geometry was used to calculate simultaneous left ventricular volume. Contractility index, pressure-volume area, external work, and potential energy were calculated during steady-state contractions. These measurements were repeated during pulsatile left atrial-aortic bypass. To induce heart failure, we injected microspheres into the left main coronary artery, and the protocol for baseline and pulsatile left atrial-aortic bypass was repeated. Despite the significant differences in the baseline contractility index (7.4 +/- 0.7 mm Hg/ml versus 4.7 +/- 0.5 mm Hg/ml), contractility index remained the same during pulsatile left atrial-aortic bypass in control and heart failure modes, respectively. Pulsatile left atrial-aortic bypass significantly decreased end diastolic volume (22% and 17%), pressure-volume area (58% and 48%) and external work (74% and 69%, all p < 0.05) during control and heart failure measurements, respectively. However, it did not change end-systolic volume or potential energy. In conclusion, asynchronous pulsatile left atrial-aortic bypass did not affect left ventricular contractile state in either the normal or failing heart. Although decreased pressure-volume area accounts for the reduction in myocardial oxygen consumption, unchanged potential energy suggested a limited unloading of the ventricle. PMID- 8196397 TI - Single-dose versus multidose cardioplegia in neonatal hearts. AB - We designed an experiment to compare single-dose versus multidose cardioplegia (calcium 0.3 mmol/L) in neonatal rabbit hearts 1, 4 and 6 weeks of age at 25 degrees C and 32 degrees C. Isolated hearts had a stabilization period of retrograde perfusion, a working period, a period of ischemia with single or multidose cardioplegia, reperfusion, and a final working period. We measured hemodynamic recovery, creatine kinase during reperfusion, and coronary vascular resistance during administration of the cardioplegic solution. One-week and 4 week-old hearts exhibited better recovery with single-dose than with multidose cardioplegia. Six-week-old hearts, on the other hand, showed better recovery with multidose cardioplegia. Four-week-old hearts at 25 degrees C showed increased creatine kinase release with multidose cardioplegia. The 6-week-old hearts tended toward lower creatine kinase release with multidose cardioplegia. Coronary vascular resistance rose with subsequent administrations in 1-week and 4-week-old hearts at 25 degrees C but did not rise in 1- and 4-week-old hearts at 32 degrees C or in 6-week-old hearts at either temperature. On the basis of hemodynamic recovery, single-dose cardioplegia appears to provide better protection than multidose cardioplegia to 1- and 4-week-old isolated rabbit hearts. Once the rabbit has reached 6 weeks of age, multidose cardioplegia has some advantage over single-dose cardioplegia, similar to the findings in adult hearts. Creatine kinase release and coronary vascular resistance data corroborate the hemodynamic findings. PMID- 8196398 TI - Clinical application of evoked spinal cord potentials elicited by direct stimulation of the cord during temporary occlusion of the thoracic aorta. AB - Evoked spinal cord potentials elicited by direct stimulation of the cord were used to monitor spinal cord ischemia in 68 patients undergoing temporary occlusion of the thoracic aorta (29 thoracic nondissecting aortic aneurysms, 9 nondissecting thoracoabdominal aneurysms, and 30 dissecting aneurysms). "Immediate" postoperative paraplegia developed in three patients and "immediate" paraparesis developed in one, whereas "delayed" paraplegia developed in two others. During aortic crossclamping, four response patterns of the spinal cord potentials were obtained: (1) no change (n = 53), (2) change with return (n = 10), (3) change with inconsistent return (n = 2), and (4) change without return (n = 3). Neurologic complications occurred in 2%, 0%, 100% of these groups, respectively. Delayed paraplegia developed on the second postoperative day in only one patient with a false-negative result, and the potentials correlated well with this patient's clinical neurologic recovery. The aortic crossclamp time was significantly longer in the patients with "change with inconsistent return" and "change without return" than in the other two groups (p < 0.01). Femoral artery pressure and the cardiopulmonary bypass flow rate were also significantly lower in these groups than in the other two groups (p < 0.02 and p < 0.01, respectively). We conclude that intraoperative monitoring of direct spinal cord responses is useful for the early detection of spinal cord ischemia for assessing the efficacy of surgical countermeasures. PMID- 8196399 TI - Do different investigators sometimes produce different multivariable equations from the same data? PMID- 8196400 TI - Documented growth of autogenous pulmonary valve translocated to the aortic valve position. PMID- 8196401 TI - Facilitation of peripheral arterial access during cardiopulmonary bypass with an audio-guided Doppler ultrasound vascular access device. PMID- 8196402 TI - Surgical treatment of coronary aneurysms with and without rupture. PMID- 8196403 TI - Atherosclerotic aneurysm of the right internal mammary artery presenting as a mediastinal mass. PMID- 8196404 TI - Complete atrioventricular canal and total anomalous pulmonary venous drainage: a rare association. PMID- 8196405 TI - Congenital ostial membrane of right coronary artery in complete transposition of the great arteries. PMID- 8196406 TI - A back-and-forth movement of the proximal intimal flap through the aortic valve. PMID- 8196407 TI - Cryopreserved pulmonary homograft for Bentall replacement of aortic root in a case of purulent bacterial endocarditis. PMID- 8196409 TI - Presenting multivariable analyses. PMID- 8196408 TI - Premature leaflet dysfunction in a tricuspid bioprosthesis. PMID- 8196410 TI - Clinical observation on needling extrachannel points in treating mental depression. AB - Totally 20 cases of mental depression were treated by needling extrachannel points with an effective rate of 90%; comparison of these cases with 21 controls treated with amitriptyline, showed no significant difference in effect (P > 0.05). Measured with Hamilton's scale, factors of anxiety somatization, cognitive disturbance, retardation, sleep disturbance and feeling of despair in both the needling and control groups showed obvious decrease in the mean value, and the change in anxiety somatization was markedly significant in the needling group as compared with that in the controls (P < 0.01). Our studies revealed that after 6 weeks of needling the power of slow wave delta decreased while that of the fast wave alpha increased, all significantly different as compared with that before and during the treatment (P < 0.05). PMID- 8196411 TI - Experience in the treatment of peripheral facial paralysis by puncturing effective points--a new system of acupuncture. PMID- 8196412 TI - Observation on the changes of plasma cardionatrion before and after microwave acupuncture in coronary heart disease. AB - This paper reports the therapeutic effect of microwave acupuncture (MWA) and its influence on the plasma level of cardionatrion. Twenty-eight cases with coronary heart disease (CHD) were systemically observed and investigated. Atrial natriuretic polypeptides (ANP) were determined by radioimmunoassay. Plasma level of ANP was elevated, the rising rate being 100%. The therapeutic effect of MWA in the 28 cases with CHD was 85.7%, the ECG improving rate was 82.2%. Effect of MWA was briefly discussed. The authors consider that the therapeutic effect of MWA in the treatment of CHD could be ascertained, and the measurement of plasma ANP concentration is a useful method and an objective parameter for further research. PMID- 8196413 TI - A clinical study on treatment of vascular complications of diabetes with the sugar--reducing and pulse--invigorating capsule. AB - The capsule is effective in replenishing qi, nourishing yin, activating blood, and resolving stasis. It can correct abnormalities in blood rheology, improve fat metabolism, enhance functioning of the islets of Langerhans, lower blood sugar, and alleviate clinical symptoms. Efficacious also against the chief vascular complications of diabetes, it helps in abating myocardial anoxia, improving left heart function, stimulating blood circulation to the brain, resisting coagulation and resolving thrombosis, also dilating the arteries of the legs. It is of some benefit in early diabetic retinopathy and renal diseases. PMID- 8196414 TI - The application of acupuncture anesthesia in cystoscopy. PMID- 8196415 TI - Treatment of sciatica with injection of Novocain into tender points along the sciatic nerve, 132 cases. PMID- 8196416 TI - Investigation on analgesic mechanism of acupoint finger-pressure massage on lumbago. PMID- 8196417 TI - Clinical observation on osteoporosis treated with traditional kidney-tonifying medicaments. AB - The method of scoring kidney deficiency symptoms and bone density was used to judge therapeutic efficacy on osteoporosis of traditional kidney-tonifying drugs. It was proved that the drugs not only improved clinical symptoms but also delayed the developmental process of this disorder. It also verified the correctness of the traditional theory that the kidney dominates the bone and generates the marrow. PMID- 8196418 TI - Effect of radix salviae miltiorrhizae on EAA and IAA during cerebral ischemia in gerbils: a microdialysis study. AB - The concentrations of amino acids (AA), stroke index and infarct area were determined in 26 gerbils which were divided into 3 groups: RSM-treated (n = 8), Saline-treated (n = 10) and sham-operated (n = 8). The levels of AA were measured with microdialysis technique in cerebral cortex. The concentrations of neurotransmitter AA, as Glu and GABA and Asp, were significantly increased during the first 60 min after CCA ligation, while the concentrations of non neurotransmitter AA, as Thr and Ser, had no significant changes. In RSM-treated gerbils, the level of Glu was significantly lower than that of the saline treated, but the GABA in RSM-treated was significantly higher than that of the saline-treated. The ratio of Glu/GABA was significantly decreased after ischemia. The RSM could improve the reduction of ratio of Glu/GABA during 0-30 min and 91 120 min after cerebral ischemia. There were statistically significant decrease in terms of stroke index in RSM-treated group when compared with saline-treated group at 24 h and 16 h after CCA ligation respectively. The RSM has a tendency to decrease the size of infarct area, but no statistical difference. The results suggest that the neurotransmitter AA involve in the pathophysiological procedures of cerebral ischemia and the RSM can attenuate dysfunctions of EAA and IAA. Furthermore, the results also imply that there may be an alternate way to treat cerebral ischemia by inhibiting the presynaptic releasing of Glu and stimulating the releasing of GABA. PMID- 8196419 TI - Free radical mechanism in enhancement of radiosensitization by SRSBR. AB - The free radical mechanism of enhancing radiosensibility by the Synergic Recipe to Strengthen Body Resistance (SRSBR) consisting of 10 Chinese drugs was studied by electron spin resonance (ESR) with spin trapping reagent--Nitroso-tert-butane (NtB) following irradiation of the Deoxy thymidine (dT) solution system by 60Co 3.7 PBq. The results showed SRSBR cannot only enhance the generation of e- aq but also enhance the production of . OH and H . after irradiation with gamma ray in dT-NtB-SRSBR aqueous solution system. These result in damage to biological molecules, attacking and killing tumor cells radiosensitized by SRSBR. The characteristics of SRSBR for radiosensitization are concluded to be increasing production of . OH and H. in comparison with the well-known radiosensitizer Misonidazole (Miso). PMID- 8196420 TI - Analysis of therapeutic effects of acupuncture on abstinence from smoking. AB - 1. Similar to other methods for abstinence from smoking, the acupuncture means has the same problems, i.e., recurrence, gradual decrease of therapeutic effects as the time goes on and unstable immediate effects. Therefore, any researches without a follow-up study are of little clinical significance. 2. Gilbey V et al pointed out that, up to now, the abstinence rates of all the methods have fluctuated between 20.0% to 35.0%, and the effective rates are around 45.0%; this is close to the average long-term effects reported in this paper. 3. Quite a number of researchers have pointed out that acupuncture is effective for many smokers who have failed to quit smoking by other methods. Research results have also indicated that the therapeutic effects of acupuncture on abstinence from smoking are similar to that of the nicotine chewing gum method and the behaviour therapy, suggesting that acupuncture is neither superior nor inferior to other methods in stopping smoking, and actually these methods can complement each other. 4. Schwartz pointed out that, the methods used in the past to quit smoking were difficult to be accepted by the majority of smokers, resulting in unsatisfactory therapeutic effects. In general, acupuncture is painless, nontraumatic, without untoward reactions, being able to inhibit the abstinence syndrome, economic, simple, etc. and eventually it is easy to be accepted by smokers. Therefore, if other methods are unsatisfactory, the acupuncture method can be tried. PMID- 8196421 TI - Recent advances in studies on traditional Chinese anti-aging materia medica. PMID- 8196422 TI - Aging, genomic entropy and carcinogenesis: implications derived from longitudinal age-specific colon cancer mortality rate dynamics. AB - Many types of cancer are intrinsically linked to the process of aging. Aging, from the perspective of the second law of thermodynamics, can be viewed as associated with the inevitable and natural increase in informational entropy of the genome. The molecular biologic basis of increasing genetic informational entropy is the inherent and variable instability of different regions of genome. Colon cancer cells have been shown to have characteristic acquired genetic abnormalities, most commonly, deletions in presumed tumor suppressor genes. Age specific colon cancer mortality rates in the US from 1958 to 1988 were subjected to longitudinal Gompertzian analysis, a method that may identify and distinguish among genetic, environmental and competitive influences upon mortality. The Strehler-Mildvan modification of the Gompertz relationship between aging and mortality can be used to determine a relative measure of the rate of increase in informational entropy (a reflection of genetic instability) for those genetic factors that are involved in the pathogenesis of colon cancer. PMID- 8196423 TI - Effects of a protein-free diet or food restriction on the immune system of Wistar and Buffalo rats at different ages. AB - The effects of a protein-free diet or food restriction on the immune system were examined in two rat strains, Wistar and Buffalo, in different age-groups. Unlike Wistar rats, Buffalo rats have an unusually hyperplastic thymus and a large number of peripheral T cells. The protein-free diet (PFD) in rats resulted in marked thymic involution together with a reduction of splenic T cells, both in number and in antibody response to sheep red blood cells. The depressive effect of the PFD on the immune system was more serious in young immature rats than in older rats, but less serious in Buffalo rats having enhanced T cell functions regardless of age. Thymic involution was also accelerated in both strains of rats by feeding them a restricted amount of the control diet containing well-balanced nutrients (food restriction, FR). In the FR experiment, no significant change was observed in immune functions of Wistar rats. A slight reduction was observed in the immune functions of Buffalo rats with FR, but absolute levels were distinctly higher in Buffalo rats than in Wistar rats even after FR. These results suggested (1) that the thymic function is sensitive to protein deficiency; (2) that a well balanced dietary condition is necessary for immunological maturation in the early stage of life and preservation of immune functions at older age; (3) that animals having higher immune functions are more resistant to malnutrition than ordinary ones. PMID- 8196424 TI - Ethylene is a selective ribosomal cistron regulator in Allium cepa epidermal cells. AB - In Allium cepa L. (onion) the number, size, and morphology of visible nucleoli per nucleus varies during cell division, growth, differentiation, storage, activation of quiescent tissue, senescence, wounding, and disease (host-pathogen interactions). Since there are two types (differentiated visually by size) of ribosomal cistrons in onion (major and minor nucleoli differ in the external spacer nucleotide sequences), we inferred that they function separately. In controls, major nucleolar organizer regions (NORs) were visible in epidermal cell nuclei as nucleoli. After exposure of the tissue to ambient conditions, these nucleoli enlarged and changed morphology. Minor NORs (when in the genome) required more than 6 h to become developed as visible nucleoli. In the ethylene treatments, the major NORs (visible nucleoli in quiescent epidermal cells) increased in size a (activation of a greater number of tandem rRNA genes) as in the controls. The minor, quiescent NORs became active and visible (activation of quiescent, inactive NORs) within 3 h. Actinomycin D, and cycloheximide, with or without ethylene, inhibited the increase in size of the major NORs, and prevented activation of the minor NORs (i.e. they did not become visible). Silver nitrate and cobalt chloride had no effect on major NORs but inhibited the appearance of minor nucleoli when combined with ethylene treatments. We infer: ethylene acts to regulate the expression of the minor NORs (selective ribosomal cistron regulation); and, other hormone(s) are involved in the regulation of the major NORs. Yellow and white sweet Spanish onions we studied had two major NORs and two minor NORs. Red sweet Spanish onions we studied had only the two major NORs. PMID- 8196425 TI - In vitro effect of hormones and growth factors on the incorporation of [3H]leucine, [35S]sulfate and [3H]proline by chondrocytes of aging mice. AB - The ability of parathyroid hormone (PTH 1-84), dexamethasone, prostaglandin E1 (PGE1), prostaglandin E2 (PGE2) and human transforming growth factor beta (hTGF beta) to stimulate the synthesis of matrical components in articular cartilage of aging mice, was studied in an organ culture system. A marked age-dependent decrease was observed in the synthesis of sulfated glycosaminoglycans (GAGs), protein, collagen digestible protein (CDP) and non-collagen protein (NCP) between 1 and 18 months of age. The addition of hTGF-beta (1 ng/ml) into the culture medium resulted in a significant (P < 0.01) increase of both protein and sulfated GAGs in condylar cartilage from animals aged 1, 3, 6 and 12 months. PGE2 (10 micrograms/ml) induced [3H]leucine and [35S]SO4 incorporation into condylar cartilage from 1, 3 and 6 months old animals. A stimulatory effect of PGE1 (10 micrograms/ml) on [3H]leucine incorporation was noted at 1 and 3 months of age. The effect of PTH appeared to be stimulatory only for protein synthesis in young (1 and 3 months old) animals, whereas it had no effect at 6, 12 and 18 months of age. In contrast, dexamethasone exerted a stimulatory effect on young adults (6 months old) and in matured (12 months old) animals, respectively and a slight inhibitory effect on young (1 and 3 months old) animals. [3H]Proline incorporation was enhanced by all the factors tested in 1-month-old animals. In cultures from 6- and 18-month-old animals only PGE1 and PGE2 appeared to be stimulatory. It is concluded that synthesis of protein, sulfated GAGs and collagen by chondrocytes from maturing and osteoarthritic senescent animals can be stimulated by hormones and growth factors. The efficiency of this response, however, varied according to the animal's age and the factor studied. PMID- 8196426 TI - [Function of the abdominal wall and development and therapy of hernias (among others: the para-colostomy hernia)]. AB - The peritoneal cavity has a fascial skeleton with musculature that is nearly always active, i.e. it has resting tone activity. During pneumoperitoneum this resting activity increases very markedly. The pelvic floor and its integrated sphincters also have a similar type of spontaneous activity depending on Onuf's nucleus in the spinal cord together with the somatic and autonomic nerves. Hernias such as umbilical hernias develop with disruption of a scar. While in a child the common inguinal hernia develops in an open vaginal processus, in an adult it develops as the result of a congenital muscular defect in the abdominal wall. A femoral hernia develops in a gap through the pressure of the resting activity of the abdominal wall. A paracolostomy hernia develops after an incision in the fascial skeleton and after pull-through of a very adipose sigma-mesosigma. It can often be treated it by pulling a slim colon segment through the innervated rectus muscle incision and closing the gap in the fascial skeleton with a running suture. Incisional or umbilical hernias can be successfully treated by suturing with a continuous nonabsorbable thread. The best therapy for inguinal hernias is suturing of the hyperplastic fascia transversalis and the reconstruction of the muscle sphincter mechanism. Bassini operated on very large hernias with hyperplastic fascia, thereby achieving excellent results. Fascial hyperplasia has been shown to follow the use of tissue expanders. PMID- 8196427 TI - [Use of autologous femoral vein in superior vena cava thrombosis. Case report and review of the literature]. AB - We report on a 52-year old male patient who underwent implantation of an insulin pump because he had diabetes and in whom superior vena cava syndrome developed as a long-term complication. After unsuccessful lysis therapy superficial femoral vein was implanted to form a bypass from the internal jugular vein to the right atrium. The postoperative course was uneventful from the aspects of both the bypass and the leg after explantation of the superficial femoral vein. The bypass is still patent 7 months after the operation, and the patient has no symptoms. Autogenous superficial femoral vein can be used successfully in the reconstruction of large venous vessels. It should be the graft of choice for young patients with benign diseases. We compare our result and those obtained with different substitutes described in the literature that have been used for reconstruction in superior vena cava syndrome. PMID- 8196428 TI - Extended bile duct resection--a new oncological approach to the treatment of central bile duct carcinomas? Description of method and early results. AB - Since the results of surgical resection and transplantation in the treatment of central bile duct carcinomas have been poor and neither radiotherapy nor chemotherapy has shown promising results, a new attempt to achieve curative resection has been made to combine liver transplantation with the Kausch-Whipple operation. With this operation the complete biliary system can be resected without touching the region of the hepatoduodenal ligament. Our intention is to avoid tumor cell spread by this "no-touch technique." Tumor cell spread is very likely to occur with the commonly used technique of close dissection near the centrally located carcinoma. In the seven patients operated on so far, we observed that the combination of total hepatectomy, partial duodenopancreatectomy and liver transplantation can be performed with fewer postoperative problems than "cluster transplantation" and probably has the same oncological benefit in terms of more radical resections at least for central biliary carcinomas. Theoretically, the radicalness of the resection should be greater than with liver transplantation or bile duct resection alone. Whether this concept helps to achieve better results in surgical treatment of early Klatskin tumors can only be evaluated after a longer follow-up. So far, six of seven patients have survived the operation without great problems and have been discharged from the hospital. The quality of life after this procedure seems to be better than with total pancreatic resection or even with replacement of the pancreas. PMID- 8196429 TI - [Second look laparoscopy after mesenteric infarct]. PMID- 8196430 TI - [Second look laparoscopy after mesenteric infarct]. AB - Second-look laparotomy is not always routinely performed after mesenteric infarction. Such operations are often not performed because of the high operative risk in aged patients and those with cardiovascular disease. We developed a minimally invasive technique for second-look laparoscopy with the aim of decreasing the operative morbidity. With the patient under general anaesthesia, the old incision is opened at the umbilicus. The running suture in the abdominal wall is lifted with a clamp and the incision line is gently reopened. A trocar with a blunt tip designed for open laparoscopy is then inserted and fixed. Following insufflation of CO2 through the trocar it is possible to explore the entire small bowel and colon. We operated on five patients after bowel resection performed for mesenteric infarction. Second-look laparoscopy was diagnostic in all but one, in whom laparoscopy failed due to massive small bowel dilatation. The technique described here is very promising and deserves further evaluation. PMID- 8196431 TI - [Angioarchitecture of the ulna and radius and their practical relevance]. AB - The periosteal and endosteal blood supply of the human ulna and radius was investigated by anatomical dissection. The main artery concerned is the anterior interosseous artery. It supplies the diaphysis of ulna and radius; its branches feed the distal one-fourths of both the ulna and the radius. The proximal one fourth of the ulna is supplied by the ulnar artery, the ulnar recurrent artery and the recurrent interosseous artery. Periosteal branches of the common interosseous artery, the ulnar artery and the recurrent interosseous artery supply the proximal one-fourth of the radius. In both bones the main branch of the nutrient artery has an ascending course. The anterior interosseous artery, as the main artery of the periosteal and endosteal supply of the human ulna and radius, is important in transplantation and reconstruction, especially with a view to reducing the rate of pseudarthrosis. When osteosynthesis is planned so called LC-DC plates should be chosen to preserve the periosteal branches. When a vascularized bone graft is taken from the forearm the vascularization of the remaining bones has to be considered. The vascularity of this area allows various options in grafting. PMID- 8196432 TI - [Experiences with internal fixation of isolated fractures of the head of the radius]. AB - The advantages of internal fixation of fractures, with the possibility of immediate resumption of the function of the fractured bone, are in contrast to the well-known complications described in the literature. These complications and our own unsatisfactory results after surgical treatment of fractures of the head of the radius induced us to carry out a randomized prospective study of primary functional treatment of such fractures without external or internal stabilization. From December 1991 through December 1992, a total of 70 patients were treated according to a strict treatment protocol at the Graz Hospital for Accident Surgery, and CT was used for observation of the healing process. The positive early results, which in 91% of all cases were classified as very good or good, the lack of complications that sometimes follow surgical treatment, the markedly earlier recovery of the patient's working capacity, and the clearly shorter--albeit somewhat more expensive--treatment period required have led us to continue using this method at our hospital and also to recommend its use elsewhere. PMID- 8196433 TI - [A concept for decreasing postoperative pain after inguinal hernia operation]. AB - In Germany approximately 150,000 inguinal hernias are surgically corrected every year. In addition to developing an optimum operation technique it is also the responsibility of a surgeon to treat pain during and after surgery. In a prospective random double-blind study, the pain after herniotomy performed with intraoperative anesthesia of the ilioinguinal and iliohypogastric nerves with a long-acting local anesthetic combined with a vasoconstrictor was compared by means of scores on a scale from 1 to 10 with pain in a control group. The results suggest that the intraoperative anesthesia reduces pain after surgery both on the day of the operation and afterwards, when the effect of the local anesthetic has decreased. An optimum pain therapy therefore has to start during surgery. Use of a local anesthetic is especially suitable. Side effects of systemic analgesics are avoided, and perioperative risks of ambulant hernia surgery can be reduced. PMID- 8196434 TI - [Holmium laser versus mechanical cartilage resection. Comparative studies in the rabbit arthrosis model]. AB - The aim of this work was to investigate and evaluate the tissue reactions after sham operation and after mechanical and holmium laser chondral debridement in a rabbit model at different postoperative intervals. In 27 rabbits an arthrosis was induced by implantation of a piece of polyethylene sheeting in one knee joint. After 5 months, distinct arthritic changes had developed. Nine animals each were randomized for sham operation, mechanical debridement, and holmium laser chondral debridement. At 1 day, 1 month, and 3 months postoperatively, three animals in each group were sacrificed and their joints examined grossly and microscopically. At 3 months after mechanical debridement the articular surface was relatively smooth, and tears and defects were filled with fibrous repair tissue. After holmium laser debridement chondral necroses were regularly found, occasionally with damage to the subchondral bone and distinct inflammation in the marrow space. The articular surface remained rough and uneven. These preliminary results suggest that use of the holmium laser is not superior to mechanical methods for remodelling and smoothing of fairly large chondral areas. PMID- 8196435 TI - [Laparoscopy versus laparotomy. An animal experiment study comparing adhesion formation in the dog]. AB - We performed laparoscopy (n = 7) or laparotomy (n = 7) for exploration of the small intestine, cecal resection with Endo-GIA or TA-30, deserosation of 2 cm2 of the abdominal wall and resection of the omentum majus in dogs. After 8 days all dogs were re-examined and the adhesions were quantified by computer-aided measurement. Laparoscopic operations were followed by significantly (P < 0.001) fewer adhesions. After conventional operations extensive adhesions to the abdominal incision and interenteric adhesions were found, together with frequent conglomerates of adhesions, intestinal kinkings or adhesive bands. Identical manipulations, such as cecal resection or deserosation of the lateral abdominal wall, led to the same frequency and severity of adhesions in both groups. Based on our results, the risk of adhesion-related complications may be reduced by the laparoscopic approach. PMID- 8196436 TI - [Motility disorders in the blind loop after Roux-en-y reconstruction. Electromyography studies in the animal experiment]. AB - Disturbances of intestinal motility, bacterial overgrowth and pancreocibal asynchrony are frequent findings in patients after Roux-en-y reconstruction (RYR). In dogs (n = 6) electromyographic recording of motility after partial gastrectomy with Roux-en-y reconstruction revealed no significant differences from controls in the Roux limb. However, changes in intestinal motility were extensively in the blind loop. The electromyographic pattern was characterized by an extreme loss of activity in the fasted and postprandial state. The activity front of the migrating motility complex occurred only in 25% of the fasting studies and was not correlated in time with motility patterns of connected small intestine. Food intake led to a significant increase in the motility index in the Roux limb (60.2 +/- 10.5), but not in the blind ending loop (27.8 +/- 4.1). Pharmacological stimulation of the hypomotile blind loop with cisapride is successful: increase of the motility index to 111.2 +/- 16.5. It might be useful in the treatment of symptomatic patients after RYR. PMID- 8196437 TI - Present and future considerations in otolaryngologic publishing. PMID- 8196438 TI - Anatomic considerations in botulinum toxin type A therapy for spasmodic dysphonia. AB - Chemodenervation by injection of botulinum toxin type A into the vocal fold(s) has become the preferred treatment for patients with adductor spasmodic dysphonia. Injection may be done either perorally or transcutaneously; each method has its advocates and advantages. The authors have used the transcutaneous transcricothyroid membrane route exclusively with satisfactory results in more than 50 patients. Temporary breathliness and aspiration are common. The preferred injection site should be as close as possible to the motor end plates of the affected muscle. The thyroarytenoid muscle end plates are distributed throughout the muscle, whereas in the lateral cricoarytenoid muscle they are located in band in the center of the muscle. The transcutaneous injection site is below and posterior to the midpoint of the vibrating vocal fold as visualized by indirect laryngoscopy. The proximity of this site to the lateral cricoarytenoid muscle suggests that postinjection breathiness and aspiration may be related to spread of botulinum toxin type A to the lateral cricoarytenoid muscle. However, it is likely that thyroarytenoid muscle paresis is mainly responsible for this side effect and that the rapid clearing of the breathy dysphonia in the face of prolonged relief of spasmodic dysphonia symptoms suggests the action of an adaptive neural response, such as axonal sprouting. Further research of this subject is warranted. PMID- 8196439 TI - Otologic manifestations of neurofibromatosis. AB - A chart review of 440 patients with neurofibromatosis seen at the Children's Hospital of Philadelphia Neurofibromatosis Clinic between 1980 and 1991 was performed to look for otologic manifestations. Neurofibromatosis 1 was present in 434 patients, and neurofibromatosis 2 was present in 6. A total of 31 otologic abnormalities related to neurofibromatosis were found in 28 patients. Neurofibromas of the external ear, including the pinna and the external auditory canal, were the most common finding. Middle ear neurofibromas were found in two patients. Acoustic neuromas were seen exclusively in patients believed to have neurofibromatosis 2. One cerebellopontine angle neurofibrosarcoma was found in a patient with neurofibromatosis 1. PMID- 8196440 TI - A comparison of preservation techniques in a vascularized rat laryngeal transplant model. AB - In earlier laryngeal transplantation studies by Takenouchi, et al., the longest ischemic interval tolerated was 45 minutes. A new animal model and enhanced preservative solutions made reassessment timely. This study evaluated two determinants of graft viability: 1. the duration of ischemia and 2. the composition of the preservative media. Three groups of viable transplants were assessed. Groups I and II were preserved with iced heparinized saline with respective ischemic intervals of 3 and 6 hours. Group III was preserved with the Wisconsin solution during a 20-hour ischemic interval. All animals were sacrificed at 24 hours. Representative sections of group I confirmed viability whereas group II exhibited both clinical and histologic evidence of irreversible vascular change. In contrast, most representative sections in group III had little demonstrable change. These data suggest that laryngeal allografts can endure prolonged ischemic intervals if properly maintained. PMID- 8196441 TI - Ultrasonography and ultrasound-guided fine-needle aspiration biopsy of head and neck lesions: a surgical perspective. AB - A head and neck ultrasound-guided fine-needle aspiration clinic was set up to determine the role of ultrasound and ultrasound-guided fine-needle aspiration in the evaluation of patients with lesions in this region. One hundred ninety-five lesions were biopsied by ultrasound-guided fine-needle aspiration in 203 patients. Ultrasound detected 2 or more lesions in 14 (48%) of 29 patients with a clinically solitary thyroid nodule. Three (8.8%) of 34 lesions thought to be within the parotid gland were determined to be external. A pronounced learning curve was evident in the technique of ultrasound-guided fine-needle aspiration, particularly for nonpalpable disease. Adequacy of sampling for each 3-month period was 71%, 89%, and 94%, respectively. Seventy-four percent of central aspirations were satisfactory compared to 54% of peripheral aspirations. Ultrasound-guided fine-needle aspiration did not alter the clinical staging of metastatic neck disease in 8 patients having 10 neck dissections but proved useful in detecting nodal recurrence in 3 irradiated necks that did not proceed to surgery. The smallest node to harbor malignancy had 4-mm maximal axial diameter. We conclude that ultrasound and ultrasound-guided fine-needle aspiration are valuable adjuncts to the clinical examination. PMID- 8196442 TI - The temporal bone in multiple myeloma. AB - Multiple myeloma is a malignant disease of the skeleton. Anatomically, any bone may ultimately come to be involved in a given case. In a literature review, no published series of temporal bone findings have been reported. In this study, oto histopathologic changes associated with multiple myeloma are analyzed and reported in 15 temporal bones from 8 patients. The bone marrow of 13 temporal bones was involved by the tumor. Osteolysis was evident in 11 temporal bones. Serous otitis media (SOM) or purulent otitis media (POM) was seen in 13 ears with 12 showing mastoid effusions. Eight ears exhibited pathological changes in inner ears, including degeneration of the organ of Corti, atrophy of stria vascularis, decreased ganglion cells, and labyrinthine hydrops. The inner ear changes were most severe in 2 patients who had otologic symptoms. Infiltration of myeloma cells was not apparent in the middle ear mucosa or the inner ears. PMID- 8196443 TI - Pulsatile tinnitus: recent advances in diagnosis. AB - Pulsatile tinnitus can often be a diagnostic problem. This communication reports the authors' experience on 100 patients with pulsatile tinnitus and describes a practical and effective diagnostic approach. Better understanding of the various etiologies of pulsatile tinnitus, coupled with the introduction of magnetic resonance angiography, in conjunction with magnetic resonance imaging, have made a major impact on the evaluation of this symptom in recent years. Cerebral angiography, previously performed on the majority of patients, is presently indicated in selected cases only. Intracranial hypertension, glomus tumors, and carotid atherosclerosis were the most common diagnoses made in our patients. PMID- 8196444 TI - Carotid artery reconstruction using superficial femoral arterial grafts. AB - The indications, consequences, and value of resection of the carotid artery as part of an extended neck dissection has been discussed for many years. Many of the earlier reports have focused on the sequelae of carotid artery ligation and tests to predict patient tolerance for the procedure. Efforts to reconstruct the carotid artery have been limited primarily to vein grafts. The authors report on 11 cases of reconstruction of the carotid artery using the patient's superficial femoral artery. The femoral artery itself is reconstructed using a Gore-Tex graft. Free autografts of the superficial femoral artery in the carotid location have been found to be an excellent size match, mechanically stronger than a vein graft, and tolerant of bacterial contamination. Arteriography in 1 case with 14 months' follow-up demonstrates long-term patency. PMID- 8196445 TI - Inner ear hair cell regeneration in a mammal: identification of a triggering factor. AB - Recent observations have shown that mammals possess a limited capacity for regeneration of inner ear sensory epithelia. It is clear, however, that a mitogenic growth factor will be necessary to up-regulate this capacity before clinical application becomes feasible. This study used in vitro cultures of adult mouse vestibular organs for assessing the mitogenic effect of transforming growth factor alpha (TGF-alpha). Sixty-one utricles and cristae were maintained in culture for 7 to 8 days. Neomycin was used to damage the hair cells. Autoradiography permitted identification of any cell which had undergone mitosis during the culture period. The proliferative response was compared in organs exposed to TGF-alpha and those maintained in the basic culture medium only. The results demonstrated that TGF-alpha significantly increased cell proliferation in the sensory epithelia and also in the marginal zones surrounding them. This finding provides a scientific basis for the concept that inner ear hair cell damage in humans may someday be reversible pharmacologically. PMID- 8196446 TI - The efficacy of topical antibiotic prophylaxis for contaminated head and neck surgery. AB - This study was undertaken to determine the feasibility of using perioperative topical antibiotics in contaminated head and neck surgery and to standardize the culture methodology (both qualitative and quantitative) which could serve as bacteriologic endpoints for evaluation. Following preliminary studies to establish oral cavity indicator organisms and the impact of a single antibiotic mouthwash dose on oral microflora, 10 consecutive patients undergoing contaminated head and neck surgery were recruited into a clinical trial where clindamycin mouthwash and intraoperative irrigation containing clindamycin were used instead of traditional parenteral antibiotics. The bacteriologic efficacy of topical clindamycin was assessed by comparing the presence of four indicator microorganisms (two aerobic and two anaerobic) cultured from two oral cavity culture sites before and after antibiotic prophylaxis. The patients included in the study underwent total laryngectomy plus neck dissection(s) for laryngeal or hypopharyngeal carcinoma from 1991 to 1992 at a large university hospital specializing in head and neck cancer surgery. The main outcome measures used were the development of a postoperative wound infection and quantitative and qualitative bacteriology of the intraoperative neck wound and postoperative oral cavity. Two aerobic and two anaerobic organisms proved useful as a practical indicator for bacteriologic efficacy. Preoperative mouthwash resulted in a 99% reduction of both aerobic and anaerobic bacteria in intraoperatively cultured neck sites. Irrigation during surgery with the clindamycin solution further reduced the bacterial neck counts by an additional 90%. There was a consistent overgrowth of Hemophilus species on postoperative oral cavity cultures. No patient developed a postoperative wound infection. A topical prophylactic antibiotic alone was efficacious and safe for patients undergoing major contaminated head and neck surgery. Culture methods for assessment of bacteriologic efficacy were reproducible and cost-effective. This pilot study furnishes the ethical and scientific basis for large-scale prospective trials comparing topical versus parenteral antimicrobial agents. PMID- 8196447 TI - The new combined surgical approach for cancer involving the base of tongue supraglottic complex. AB - The base of the tongue, valleculae, preepiglottic space, and supraglottic area of the larynx develop from an unpaired central area, i.e., "hypobranchial eminance," unlike oral tongue and vocal cords, which are independently unilateral and paired in character. These areas should be known as "base of tongue-supraglottic complex." Lymphatic criss-cross is common in this area. This paper delineates the usefulness of the combined surgical procedure. The extensive cancer in the base of tongue-supraglottic complex has represented a challenge to the head and neck surgeon. A combined procedure, i.e., supraglottic laryngectomy with a deep and extensive sagittal surgical incision made directly through the lip-mandible-oral tongue, provides wider exposure without severing any major nerves or blood vessels, and the vulnerable bilateral lymph bearing area of the neck can be addressed adequately for elective or curative neck dissection. Preoperative dental assessment, visual and palpatory assessment of tumor extent under anesthesia (EUA) helps in careful patient selection. Rehabilitation is expected to take longer, but not hospitalization, which is understood in surgical resections of this magnitude. The Tata Memorial Hospital experience with this new surgical approach is described in detail. PMID- 8196448 TI - Disappearance of epiglottitis during large-scale vaccination with Haemophilus influenzae type B conjugate vaccine among children in Finland. AB - Surveillance of blood-culture-proven epiglottitis was conducted in Finland from 1985 through 1992. Among children (< 16 years), all bacteria causing epiglottitis, and among adults, Haemophilus influenzae were included. H influenzae type b (Hib) caused 226 (97%) of cases among children. Among adults with H influenzae epiglottitis (total of 20), 19 were caused by Hib. In 1986, vaccine trials with Hib-conjugate vaccines started in Finland, with vaccination coverage of 94% to 98% of infants. Vaccinations did not yet have an effect on the occurrence of epiglottitis in 1985 or 1986 when the annual incidence among children was 5.3/100,000, among those less than 5 years of age was 13.2/100,000, and among adults was 0.08/100,000. In 1987 through 1992 the proportion of vaccinated children increased steadily while the incidence of Hib epiglottitis decreased from 50 to 60 cases seen annually in 1985 and 1986 to 2 cases in 1992. There was no increase in the occurrence of epiglottitis caused by other pathogens. In conclusion, there is now a safe and efficient way to prevent the majority of epiglottitis cases among children with the new Hib-conjugate vaccines. PMID- 8196449 TI - Experimental revascularization of airway segments. AB - A series of experiments was conducted to assess the possibility of revascularizing tracheal autografts with the rabbit lateral thoracic fascial flap. Injection studies and histological evaluation displayed optimal revascularization and reepithelialization of the graft after 2 weeks. PMID- 8196450 TI - Prevalence of microfissures in the human temporal bone: a report of 1000 temporal bones. AB - A total of 1000 human temporal bones were studied to determine the prevalence of two microfissures: 1. the one between the facial canal and the vestibule, 2. the microfissure between the round window niche (RWN) and the posterior semicircular canal (PSC). Additionally, this study compares the prevalence according to temporal bone age and sex. The microfissure between the facial canal and the vestibule was observed in 470 (47%) temporal bones, with a bilateral presence of 77.2%. The prevalence of this microfissure increases linearly with age. It was not found in any bone within the 0 to 2 age group. It was present in 3 (7.3%) bones from the 2 to 9 age group, as opposed to 374 (54.8%) bones from the 40 and over group. The microfissure between the RWN and the PSC was detected in 915 (91.5%) temporal bones. This second microfissure was found to be an overwhelmingly bilateral entity. The prevalence of this other microfissure also increases with age. This microfissure was also not present in any temporal bone within the 0 to 2 age group. It was found in 28 (68.3%) bones from the 2 to 9 age group, in contrast to 678 (99.4%) temporal bones from the 40+ group. PMID- 8196451 TI - Papillary thyroid carcinoma: correlations between prognosis, age, and clinicopathological and histomorphological findings. AB - The age influence on the prognosis of papillary thyroid carcinoma was analyzed in a group of 67 patients. A marked decline in cause-specific survival was found for patients older than 60 years of age at the time of diagnosis. In order to find a tumor-biological explanation of the prognostic difference between patients below and above 60 years of age, several clinicopathological and histomorphological features were analyzed. Tumors from patients older than 60 years of age showed significantly more mitotic activity and nuclear polymorphism, fewer psammoma bodies, and more frequent extrathyroidal invasion and distant metastases. The results indicate that 60 years of age the time of diagnosis may be the "prognostic break-point" for papillary thyroid carcinoma. PMID- 8196452 TI - Tinnitus suppression by electrical stimulation of the cochlear wall and by cochlear implantation. AB - Some recent studies have reported on tinnitus suppression by electrical stimulation of the cochlear wall and by cochlear implant. In the present study, the degree of tinnitus in cochlear implant candidates was determined and the effects of promontory stimulation and cochlear implantation on tinnitus were investigated. Of the cochlear implant candidates, all of whom were either severely hearing impaired or totally deaf, 87% experienced tinnitus. When electrical stimulation was applied to the cochlear wall (promontory stimulation test), tinnitus was abolished in 23% and improved in 46% of the patients. Thus, electrical stimulation of the cochlear wall effectively suppressed tinnitus in 69% of the patients. Following cochlear implantation, tinnitus was abolished in 35% and decreased in 42%. Thus, intracochlear electrical stimulation was effective for treatment of tinnitus in 77% of the patients. The suppression of tinnitus continued for several hours after the patients switched off the implant device. In 60% of the patients whose tinnitus was suppressed or abolished after the cochlear implant surgery, tinnitus was also suppressed in the contralateral ear. PMID- 8196453 TI - Human papillomavirus and normal nasal mucosa: detection of human papillomavirus DNA in normal nasal mucosa biopsies by polymerase chain reaction and in situ hybridization. AB - To determine a possible etiological role of human papillomavirus (HPV) in sinonasal papillomas and squamous cell carcinomas, it is necessary to investigate normal nasal mucosa of healthy persons for the presence of HPV. The material in the present study consists of 21 biopsies taken from the inferior concha of 21 otherwise healthy persons who underwent surgery for nose fractures or nasoseptal deviations. In addition, five inferior conchae were obtained from persons who had died of non-neoplastic diseases. HPV was not detected in any of these specimens, either by polymerase chain reaction or by in situ hybridization. Histologic evaluation showed that squamous metaplasia was a common finding in the biopsies. The presence of HPV in sinonasal papillomas and carcinomas may indicate that HPV is an etiological factor in these lesions. PMID- 8196454 TI - Maxillary sinus hypoplasia and vertical dystopia of the orbit. PMID- 8196455 TI - Ventilation with the Combitube during tracheotomy. PMID- 8196456 TI - Revision endoscopic sinus surgery: six friendly surgical landmarks. PMID- 8196457 TI - Compound subscapular system free-tissue transfer for facial reanimation and resurfacing: a case report. PMID- 8196458 TI - New keel fixing technique for endoscopic repair of anterior commissure webs. PMID- 8196459 TI - Spanner malleus-stapes/footplate assembly. AB - A simply prepared and implanted ossiculoplasty prosthesis is described for use when the malleus is suited to assembly procedures. The one versatile hydroxylapatite and Teflon model is suitable for both the malleus-stapes and malleus-footplate role. Clinical trials of 80 prostheses in place for 5 to 18 months have confirmed excellent surgical handling properties combined with optimal audiological results. PMID- 8196460 TI - Auricular reconstruction using postauricular myocutaneous flap. PMID- 8196461 TI - Directory of otolaryngological societies. PMID- 8196462 TI - Uniformity of results reporting in head and neck cancer. PMID- 8196463 TI - Tracheostomal stenosis after total laryngectomy. PMID- 8196464 TI - The intranasal ethmoidectomy: evolution and an assessment of the procedure. PMID- 8196465 TI - [Fecal blood screening lowers mortality from intestinal cancer]. PMID- 8196466 TI - [Rational therapy of salmonella enteritis]. AB - One prerequisite for an effective treatment of a salmonella enteritis with antibiotics is a reliable direct antibacterial activity of the drug. In comparison to most of all other usual antibiotics quinolones, especially ciprofloxacin, fulfill these conditions, because its activity is high and resistance of Salmonella against quinolones is extremely rare. Since quinolone resistance is never plasmid coded, there will be even in the future no obvious risk of spreading of resistant strains. Another prerequisite is that the drug is able to have access to the site of residence of the microorganism. Salmonella spp. possess the virtue to penetrate into host cells and to reside and even to multiply there. Curing can be achieved only when these intracellular bacteria are eradicated. Elimination of Salmonella in the gut lumen alone is not satisfactory. Only few antibiotics are taken up into host cells, which could explain the rather frequent failure rate of antibiotic therapy of salmonella enteritis. Quinolones on the other hand are accumulated in host cells and in addition are able to act upon bacteria in this peculiar intracellular environment. Among the various quinolone derivatives ciprofloxacin is particularly qualified because it is excreted via the intestine to a considerable extent, so that high concentrations may be achieved at the proper site. The clinical experience demonstrates indeed that in most instances a rapid amelioration of the acute disease is achieved and in chronic carriers a high rate of curing occurs. Thus, for microbiological, pharmacological, and clinical reasons one can recommend ciprofloxacin for the treatment of enteric infections with Salmonella spp. PMID- 8196467 TI - [Lansoprazole--profile of a new proton pump inhibitor]. AB - Lansoprazole, a new proton pump inhibitor, selectively inhibits the H+/K(+) ATPase. Its inhibitory effect on basal and gastrin stimulated gastric acid secretion is equal to omeprazole and stronger than that of H2-receptor antagonists. Healing rates concerning gastric and duodenal ulcers and refluxesophagitis are significantly higher compared to H2-receptor antagonists and at least comparable to omeprazole. Regarding pilot studies in H. pylori eradication therapy, lansoprazole in combination with various antibiotics is expected to show good eradication rates. Considering its excellent safety and interaction profile lansoprazole is effective and safe in treating acid related disorders. PMID- 8196468 TI - [Omeprazole modified antibiotic therapy of Helicobacter pylori infection: can clarithromycin be replaced by roxithromycin?]. AB - Thirty-five consecutive patients (median age: 50 years, 17 men and 18 women) suffering from Helicobacter pylori associated peptic ulcer disease (duodenal ulcer: n = 15, gastric ulcer: n = 13) or severe functional dyspepsia (n = 7) were enrolled in a two-center clinical trial and treated with omeprazole 20 mg bid preprandially and roxithromycin 300 mg bid postprandially over two weeks. After cessation of the study medication, ulcer patients received a full dose H2-blocker treatment up to the final examination four weeks later. All patients completed the trial without contravening the protocol. Side effects were not recorded. The overall proportion of cure of Helicobacter pylori-infection was 29% (10 out of 35 patients) without statistically significant difference between the two participating centers (center I: 7 out of 20 patients [35%], center II: 3 out of 15 patients [20%]; p = 0.33). We conclude from our results that omeprazole plus roxithromycin is an ineffective treatment schedule with regard to cure of H.pylori-infection in patients with peptic ulcer disease or dyspepsia. PMID- 8196469 TI - [Severe complication in endoscopic ligation of esophageal varices]. AB - The case of an esophageal perforation of a 47 year old patient with cirrhosis of the liver is described as a complication of endoscopic band ligation of esophageal varices. It is discussed how to avoid this complication. PMID- 8196471 TI - [Chronic inflammatory bowel diseases]. PMID- 8196470 TI - [Biliary pseudocyst as a rare complication of choledocholithiasis]. AB - Biliary pseudocysts, so-called biliomas are reported to be an extreme rarity and mostly arising posttraumatic. We report on a case of symptomatic choledocholithiasis 7 years after cholecystectomy. The course was complicated by formation of a biliary pseudocyst. The 71-year-old, septic patient could not be operated because of pulmonal and cardiac high risks. He could be treated successfully by conservative procedure via endoscopic papillotomy, stone extraction and percutaneous, sonographic controlled drainage of the biliary pseudocyst. PMID- 8196472 TI - Hormonal modulation of extinction responses induced by sexual steroid hormones in rats. AB - A functional interrelation between the nervous and endocrine systems has been established. However, few studies have dealt with the effects of sexual steroids on learning and memory. The aim of this work was to determine whether sexual steroid hormones could modulate the extinction response of a passive avoidance conditioning in rats. Male Wistar rats, randomly assigned to five groups, two controls and three experimental groups, were submitted to a one-trial passive avoidance conditioning and tested for their retention 24 hr after and during 10 weeks. One control group received no treatment at all, the other received vegetable oil, and the three experimental received 20 mg of testosterone enanthate, 0.8 mg estradiol valerate, or 4 mg nandrolone decanoate, respectively. All substances were applied in a 0.3 ml volume, 24 hours before training and before testing for retention each week during 10 weeks. Results indicate that the extinction process is modulated by these hormones, since testosterone and estradiol facilitate extinction, whereas the anabolic androgen produced a resistance to the extinction process. PMID- 8196473 TI - Blockade of morphine analgesia by an antisense oligodeoxynucleotide against the mu receptor. AB - The recent cloning of mu, delta and kappa 1 opioid receptors has provide opportunities in the study of their pharmacology. Using an antisense strategy developed against delta and kappa 1 opioid receptors, we designed an antisense oligodeoxynucleotide directed against the 5'-untranslated region of MOR-1 clone, 51-70 bp upstream from the initiating ATG. Microinjection of this antisense oligodeoxynucleotide directly into the periaqueductal gray on Days 1, 3 and 5 completely blocked the analgesic actions of morphine administered into the periaqueductal gray on Day 6 (p < 0.001), 24 hr after the last antisense treatment. Rats treated with vehicle or with a mismatch oligodeoxynucleotide in which two pairs of bases from the antisense sequence had been switched were not significantly affected. These findings confirm the pharmacological relevance of the MOR-1 clone and its involvement in morphine's actions. PMID- 8196474 TI - Animal studies on the role of 50/60-Hertz magnetic fields in carcinogenesis. AB - A number of epidemiological studies have suggested that exposure to 50/60-Hz magnetic fields (MF) from power lines and electrical equipment may be associated with a modestly increased incidence of various types of cancer. Laboratory studies have indicated that nonionizing radiation has no mutagenic effect, i.e. does not initiate cancer. Thus, if 50/60-Hz MF are truly associated with an increased risk of cancer, then these fields must act as a promoter or co-promoter of cancer in cells that have already been initiated. This paper reviews the evidence produced by animal studies. As shown in this review, the available animal data on 50/60-Hz MF exposures seem to indicate that intermediate MF exposure exerts co-promoting effects in different tumor models, particularly cocarcinogenesis models of breast cancer, while chronic (up to life-time) exposure may exert promoting effects on "spontaneous" development of certain tumors. The tumor promoting or co-promoting effects of 50/60-Hz MF exposure found in several animal studies could relate to actions of MF on gene expression, immune surveillance, and Ca2+ homeostasis as demonstrated by in vitro experiments in cell cultures. However, the most plausible evidence for an in vivo effect of MF exposure which could be related to tumor promotion is reduction of circulating levels of melatonin, i.e. a hormone which is inhibitory to the growth of a wide range of cancers, particularly breast cancer. Animal studies have shown that 50 Hz MF exposure at flux densities as low as 0.3-1 mu Tesla significantly reduces nocturnal melatonin levels in plasma. While decrease of melatonin levels alone could explain tumor promoting or co-promoting effects of MF exposure, recent data indicate that MF exposure also impairs the effects of melatonin at the cellular level. Thus, the oncostatic effect of melatonin on cell proliferation of a human breast cancer cell line was antagonized by 60-Hz MF exposure at a flux density of about 1 mu Tesla. All these data indicate that interactions between 50/60-HZ MF exposure and melatonin may be the key mechanism of any carcinogenic effects. Although the existing experimental evidence is still insufficient for discerning a cause-effect relationship for MF exposure and human disease or injury, it does suggest the need for further laboratory research under well-defined laboratory exposure conditions to allow for a realistic assessment of the possible health risks and their magnitude. PMID- 8196475 TI - Suppression of plasminogen activator inhibitor type 1 release from cultured human umbilical vein endothelial cells by basic fibroblast growth factor. AB - We investigated the release of plasminogen activator inhibitor type 1 (PAI-1) from cultured vascular endothelial cells after exposure to basic fibroblast growth factor (bFGF). Treatment with human recombinant bFGF of confluent cultures of endothelial cells derived from human umbilical vein resulted in a reduction of the accumulation of PAI-1 antigen (PAI-1:Ag) in the conditioned medium. The suppressive effect of bFGF completely disappeared in the presence of anti-bFGF antibody. The reduction of endothelial PAI-1:Ag release induced by bFGF was suggested to be independent of intracellular accumulation of cyclic AMP. On the other hand, nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway of arachidonic acid metabolism, suppressed the spontaneous release of PAI 1:Ag by itself; in the presence of NDGA, bFGF failed to further suppress the PAI 1:Ag release. The effect of bFGF and indomethacin, an inhibitor of the cyclooxygenase pathway, was additive on the PAI-1:Ag release. The present data suggest that bFGF reduces the endothelial PAI-1:Ag release via suppression of the putative lipoxygenase pathway which up-regulates a part of the spontaneous PAI 1:Ag release. PMID- 8196476 TI - Pancreastatin molecular forms in normal human plasma. AB - Circulating molecular forms with pancreastatin (PST)-like immunoreactivity in plasma from normal subjects were examined. An immunoreactive form corresponding to a human PST-like sequence [human chromogranin-A-(250-301)] (hPST-52) and a larger form (mol wt 15-21 kDa) were detected by gel filtration of plasma from normal subjects. On high performance liquid chromatography, predominant immunoreactive forms coeluted with the three larger forms which were purified from the xenograft of human pancreatic islet cell carcinoma cell line QGP-1N cells and with synthetic hPST-52. The fraction containing larger forms purified from xenograft of QGP-1N cells had biological activity equivalent to that of hPST 52 on the inhibition of pancreatic exocrine secretion. These results suggest that the larger molecular forms as well as hPST-52 may be physiologically important circulating forms of PST in human. PMID- 8196477 TI - Taurine-induced diuresis and natriuresis in cirrhotic patients with ascites. AB - Taurine is a non-protein sulfur amino acid widely distributed in mammalian tissues, with poorly understood functions. Taurine administration has a variety of hemodynamic effects, including improvement of cardiac function and suppression of sympathetic activity. Increased urinary volume and sodium excretion have been reported in taurine-fed hamsters. Since patients with ascitic liver cirrhosis have severe hemodynamic and renal abnormalities potentially sensitive to taurine feeding, we evaluated the effects of the i.v. infusion of taurine on urinary flow and sodium excretion and on the hormones involved in the control of hydrosaline homeostasis. Eight cirrhotic patients with tense ascites were given an i.v. bolus of taurine (16 mumoles in 40 ml of saline). The next day patients were given saline only, as a control. Diuresis, urinary sodium and plasma renin activity, aldosterone, atrial natriuretic peptide and arginine vasopressin were measured for the following 6 hrs. Plasma taurine increased ten fold after infusion, then decreased exponentially. No side effects were recorded. After taurine, but not after saline, there was a prompt and significant increase in both urinary volume and sodium excretion. Diuresis increased from 340 +/- 43 to 817 +/- 116 microliters/min (p < 0.01); urinary sodium from 13.8 +/- 3 to 26.3 +/- 4 mumoles/min (p < 0.05). Both values returned to normal after 2-3 hrs. Taurine infusion caused a concomitant significant decrease in plasma renin activity (from 7.7 +/- 2.2 to 4.3 +/- 1.9 ng/ml/hr, p < 0.05) and aldosterone (from 588 +/- 47 to 348 +/- 89 pg/ml, p < 0.05), but no changes in atrial natriuretic peptide and arginine vasopressin. We conclude that i.v. taurine infusion in ascitic cirrhosis promotes a transient diuresis and natriuresis, apparently through the inhibition of the renin-aldosterone axis. PMID- 8196478 TI - Identification of alpha 1-adrenoceptor subtypes present in the human prostate. AB - alpha 1-Adrenoceptors (ARs) play an important role in mediating human prostatic smooth muscle contraction. In the present study cDNA fragments covering different domains of 3 alpha 1-AR subtypes (alpha 1b, alpha 1c and alpha 1d) were generated from human prostate by reverse transcription coupled to the polymerase chain reaction (RT-PCR). The reconstituted partial sequence (349 amino acids) of the human prostatic alpha 1c-AR PCR products showed 94% identity at the amino acid level with that of the corresponding region of the cloned bovine brain alpha 1c AR. Using human alpha 1-AR subtype selective cDNA probes in Northern blot analysis, the co-expression of mRNA transcripts corresponding to alpha 1b-, alpha 1c- and alpha 1d-AR subtypes was detected in 4 different regions (apex, base, periurethra and lateral lobe) of the human prostate. Competitive inhibition experiments of [3H]-prazosin binding to membrane preparations of human prostate revealed that the non-selective alpha 1-subtype antagonist, alfuzosin, produced a monophasic inhibition curve, whereas oxymetazoline produced a 2-component inhibition curve with pKi values of 8.54 and 5.46. The high-affinity alpha 1-AR component of the oxymetazoline inhibition curve was predominant (57%-66%) and showed an affinity for oxymetazoline comparable to that of the alpha 1c-AR subtype. As such our results illustrate the expression of different alpha 1-AR subtypes in human prostate and importantly that alpha 1c represents the predominant alpha 1-AR subtype present in this tissue. PMID- 8196479 TI - The use of a scanning proton microprobe to observe anti-HIV drugs within cells. AB - A series of inorganic polyanions (viz. heteropolytungstates) has been shown to have antiviral activity but there was no evidence to indicate that the drugs reached their site of antiviral (HIV) activity intact. We have shown that with a scanning proton microprobe it is possible to analyse the metal content of individual cells (PBLs) treated with such a polyoxometalate drug and to determine the atomic ratio of the metals within the cell. This was found to be near that in the drug. The distribution of the metals (tungsten and cobalt) within the cell was measured and it was shown that both metals were located in the same region within the cell. These findings would suggest that the drug had entered the cells intact. PMID- 8196480 TI - Characterization of two endothelin converting enzymes and their preference for big endothelin-1 and -2 as substrates. AB - Two proteolytic activities that convert big ET to ET at neutral pH were identified in solubilized membranes prepared from rat lung. The endothelin converting activities were partially purified by using A80227 ((2S,3R,4S)-2-([N acetylcyclohexylalanyl-isoleucyl]amino)-1-(2-nap hthyl)-3,4-dihydroxy-6 methylheptane) coupled to an affinity-gel column (Affigel), and subsequently by concanavalin-A immobilized gel chromatography. An endothelin-converting activity was identified in the fraction containing proteins that did not bind to A80227 Affigel. This protease was sensitive to phosphoramidon, soybean trypsin inhibitor, and chymostatin, and preferred big ET-1 or big ET-2 as its substrate over bit ET-3. A second endothelin-converting activity was identified in the fraction containing proteins that bound to the A80227-coupled gel and was eluted by raising the pH. This protease exhibited activities throughout a range of pH 5.5-9.5, was inhibited by pepstatin A and A80227, and also preferred big ET-1 or big ET-2 over big ET-3 as its substrate. Both enzymes were glycoproteins based on their binding to concanavalin-A immobilized gel and were readily eluted by a buffer containing 0.5 M manopyranoside. The results from the pH and protease inhibitor profiles suggesting that these two ET-converting activities extracted from rat lung membranes are distinct and are different from the previously reported endothelin-converting enzymes. PMID- 8196481 TI - An improved method to calculate adipose tissue interstitial substrate recovery for microdialysis studies. AB - We simultaneously compared the conventional, time-consuming point of no net flux method for calculation of interstitial substrate recovery necessary for in vivo microdialysis studies with a simple isotopic method using rat epididymal fat pads. The recovery (%) calculated with the conventional method and the isotopic method for glucose (7.4 +/- 1.1 vs. 6.6 +/- 0.6), glycerol (23 +/- 4 vs. 26 +/- 5) and lactate (40 +/- 8 vs. 38 +/- 5), respectively, were not significantly different. Moreover, the overall correlation coefficient (N = 25) between the methods was 0.87, p < 0.001. We therefore conclude that the methods yield comparable results, and the more convenient isotopic method should become the method of choice for determining adipose tissue interstitial recovery for glucose, lactate and glycerol. PMID- 8196482 TI - Does cyclo(His-Pro) act like amphetamine? AB - In many pharmacologic tests, cyclo(His-Pro) (CHP) appears to act like a dopaminergic agonist and augments the actions of amphetamine (AMP). Therefore, to determine whether CHP is an AMP-like peptide, a comparison between CHP and AMP was made using four separate tests known to be AMP-responsive. These include, food intake, locomotor activity, dopamine uptake and modulation of binding sites for amphetamine and mazindol. A decrease in food intake and increase in spontaneous locomotor activity and stereotypy was observed after peripheral administration of amphetamine but not CHP. Chronic CHP administration resulted into a decrease in striatal amphetamine - and increase in mazindol-binding sites; in contrast, chronic amphetamine decreased both amphetamine - and mazindol binding sites. These results show a clear dissociation between CHP and AMP suggesting that CHP is not an amphetamine-like peptide. PMID- 8196483 TI - Carbamazepine affects triiodothyronine production and metabolization in rat hippocampus. AB - The effects of subchronic administration of carbamazepine on thyroid hormone metabolism were investigated in the hippocampus in adult male rats at two different measuring times (4 a.m. and 8 p.m.). Carbamazepine enhanced the activity of 5'II-deiodinase, which catalyzes the deiodination of the prohormone T4 to the active compound T3, at 8 p.m., but not at 4 a.m. The activity of 5III deiodinase, which catalyzes the further deiodination of the active hormone T3 to its metabolite 3,3'T2, was inhibited at 4 a.m. but not at 8 p.m. These effects of carbamazepine on intracellular thyroid hormone metabolism in the hippocampus should theoretically lead to a rise in T3 production. It remains to be investigated whether they are somehow involved in the as yet unknown mechanisms underlying the anticonvulsant/mood-stabilizing effects of carbamazepine. PMID- 8196484 TI - Prodepin: a new product of the adrenomedullin (ADM) gene has systemic vasodilator activity. AB - The purpose of the present study was to investigate the effects of products of the ADM gene other than ADM on systemic hemodynamics in the anesthetized rat, rabbit, piglet, cat and dog. Bolus intravenous (i.v.) injections of rat proADM22 41 (3-30 micrograms) significantly decreased systemic arterial pressure (SAP) and systemic vascular resistance in the anesthetized rat. Unlike ADM, rat proADM22-41 markedly increased cardiac output in the rat. Bolus i.v. injections of human proADM22-41 up to 500 micrograms had not effect in all species studied and rat proADM22-41 had no effect in species other than the rat. The present data suggest that rat proADM22-41 is a novel product of the ADM gene other than ADM and possesses marked systemic vasodilator activity. The present data also suggest that the hemodynamic activity of this peptide is species specific. PMID- 8196485 TI - Evidence for a dopamine receptor subtype sensitive to combination of D1 with D2 antagonist in measurement of G-protein activity using rat striatal membranes. AB - In rat striatal membranes, various kinds of dopamine receptor agonists stimulated low-Km GTPase activity in a concentration-dependent manner. This stimulation by bromocriptine, pergolide and apomorphine was partially inhibited by sulpiride (SUL), a D2-selective antagonist, markedly inhibited by combination of SUL with SCH 23390 (SCH), a D1-selective antagonist, and not modified by SCH alone. The stimulation by BAM-1110 was resistant to SUL or SCH alone but abolished by combination of SUL with SCH. These findings suggest the presence of another subtype of a dopamine receptor in a functional in vitro bioassay system in rat striata. PMID- 8196486 TI - Differential effects of chloral hydrate and pentobarbital sodium on cocaine induced electroencephalographic desynchronization at the medial prefrontal cortex in rats. AB - We evaluated the effects of two anesthetics on the cocaine-induced electroencephalographic (EEG) desynchronization in male, Sprague-Dawley rats. One group was anesthetized with chloral hydrate (400 mg/kg, i.p., 80 mg/kg/h i.v. supplement; group A). The other group was anesthetized with pentobarbital sodium (50 mg/kg, i.p., 10 mg/kg/h i.v. supplement; group B). The degree of EEG desynchronization after cocaine administration (1.5 mg/kg, i.v.) was expressed as an increase in the mean power frequency (MPF) and a decrease in the root mean square (RMS). These maximal increases and decreases were observed to be larger in group A (MPF: 43.3 +/- 7.0% increase; RMS: 47.4 +/- 5.0% decrease) than in group B (MPF: 17.8 +/- 3.6% increase; RMS: 19.2 +/- 2.5% decrease). Our laboratory previously proved that dopaminergic neurotransmission at the medial prefrontal cortex (mPFC) participated in the cocaine-induced EEG desynchronization and that both D-1 and D-2 receptors were involved in the process. Therefore, in vivo microdialysis coupled with high performance liquid chromatography was used to quantify the changes of extracellular dopamine (DA) concentrations at the mPFC for 90 minutes at 10 minute intervals after 1.5 mg/kg cocaine i.v. injection. The extracellular DA increases in both groups was rapid and reached the maximal peak within 10 min. There was no significant difference in the maximal increase of DA between groups (group A: 375.2 +/- 35.77% versus group B: 332.2 +/- 16.69% over basal value). These results suggest that different anesthetics may differentially affect cocaine-induced EEG desynchronization and this difference has no bearing on the DA response in the mPFC. PMID- 8196487 TI - Differential mediation of cold water swim stress-induced antinociception by delta opioid receptor subtypes in diabetic mice. AB - The involvement of delta-opioid receptor subtypes in cold water swim stress (CWSS)-induced antinociception in diabetic mice was compared with that in non diabetic mice. Three-minute swim stress produced significant antinociception in both diabetic and non-diabetic mice as determined by the tail-pinch test. However, the extent of CWSS-induced antinociception in diabetic mice was significantly greater than that in non-diabetic mice. Pretreatment with naltriben, a selective delta 2-opioid receptor antagonist, significantly attenuated CWSS-induced antinociception in both non-diabetic and diabetic mice. In contrast, although 7-benzylidenenaltrexone, a selective delta 1-opioid receptor antagonist, significantly attenuated CWSS-induced antinociception in diabetic mice, it had no effect in non-diabetic mice. These results suggest that CWSS-induced antinociception in non-diabetic mice is mediated by delta 2-opioid receptors, whereas CWSS-induced antinociception in diabetic mice is mediated by both delta 1- and delta 2-opioid receptors. Furthermore, the enhanced CWSS induced antinociception in diabetic mice may be due to the activation of delta 1 opioid receptors. PMID- 8196488 TI - Relative steady-state expression of the different post-translational products of p21-H-ras from normal rat tissues. A 2D-western immunoblot study. AB - Proteins extracts from rat cell lines or tissues expressing normal or activated c H-ras genes, or normal N-ras gene were submitted to westernblot analysis with an anti-H, K, N p21-ras antibody. This showed that p21-H-ras products resolved into four spots (a, b, c, d) that are readily distinguishable from the normal p21-N ras products (spots e, f, g), and also from two other products (spots a', b') present in extracts from cells which overexpress a Val12-mutated H-ras gene. Considering metabolic isotopic labeling and cell fractionation, we were able to establish the correspondance of spots a, b, c, d with the known steps of the sequential post-translational processing (farnesylation, further carboxymethylation and ultimate palmitoylation) of p21-H-ras. The palmitoylated product predominates in normal brain and still more in normal adult liver tissues, whereas its relative level decreases in proliferating liver cells. PMID- 8196489 TI - Muscarinic receptor selectivities of 3-Quinuclidinyl 8-xanthenecarboxylate (QNX) in rat brain. AB - We have determined the binding of (R)-3-Quinuclidinyl 8-xanthenecarboxylate to muscarinic acetylcholine receptor preparations from rat cortex, hippocampus, caudate/putamen, thalamus, pons and colliculate bodies. The competition curves determined with [3H]quinuclidinyl benzilate as the radioligand are well described by a two site model with a difference in affinity between the two sites of 12 fold. The proportions of high affinity site vary from 100% in the caudate/putamen to 0% in the pons/medulla. The selectivities are different from those measured by pirenzepine and are consistent with QNX exhibiting similar affinity for the M1, M3, and M4 receptors with lower affinity for the M2 receptor. This assignment was confirmed by determining the affinities of QNX for the cloned receptor subtypes. PMID- 8196490 TI - Discriminative stimulus and response rate-decreasing effects of kappa opioids: antagonism by naloxone. AB - The present study examined the discriminative stimulus and response rate decreasing effects of kappa opioids in pigeons trained to discriminate a 0.017 mg/kg dose of bremazocine from saline. Bremazocine, spiradoline, CI977, U69,593 and U50,488 substituted completely for the bremazocine stimulus in a dose dependent and naloxone-reversible manner. Apparent pA2 values (range, 6.01-6.81) of naloxone against the discriminative stimulus effects of these kappa opioids were smaller than those reported previously in the pigeon for naloxone against the discriminative stimulus effects of various mu opioids. Bremazocine, CI977, spiradoline and U69,593 also decreased rate of responding in a dose-dependent and naloxone-reversible manner. The apparent pA2 values (range, 6.25-6.44) for naloxone against the rate-decreasing effects of bremazocine, CI977 and U69,593 were not different from the apparent pA2 values for naloxone against their discriminative stimulus effects. An apparent pA2 for naloxone against the rate decreasing effects of spiradoline could not be determined due to the shallow slope of the Schild plot. Although the rate-decreasing effects of U50,488 were antagonized by naloxone, the degree of antagonism was small and not dose dependent. These findings indicate that the discriminative stimulus and rate decreasing effects of some kappa opioids are mediated by similar mechanisms and that a non-opioid mechanism may contribute to the rate-decreasing effects of spiradoline and U50,488. PMID- 8196491 TI - Interaction of iodinated quinuclidinyl benzilate enantiomers with M3 muscarinic receptors. AB - We examined the interaction of 3-quinuclidinyl-4-iodobenzilate enantiomers, (RR)- and (SS)-IQNB, relatively receptor-active and -inactive, respectively, with M3 muscarinic receptors (mAChRs) in rat parotid acinar cells in vitro. This stereospecific antagonist pair has often been used for in vivo studies of mAChRs. There was a 16-fold difference in the ability of (RR)- and (SS)-IQNB to bind in vitro to mAChRs; Ki values estimated by competition with N-methylscopolamine were 5.3 and 84.2 nM, respectively. However, the ability of these antagonists to inhibit carbachol-stimulated inositol trisphosphate formation (Ki values determined by Schild analyses) was more similar, 16.3 and 47.7 nM, respectively for (RR)- and (SS)-IQNB. These data suggest that while it may be useful to employ this antagonist pair to evaluate some mAChR subtypes in vivo, it is difficult to use them in studies of M3-mAChRs. PMID- 8196492 TI - Effects of cell density and conditioned medium on alpha 2A adrenergic receptor density and messenger RNA abundance in HT-29 cells. AB - We have examined the relationship between cell density and alpha 2A adrenergic receptor number and mRNA in HT-29 cells. alpha 2A receptors increased with increasing cell density from 75 +/- 25 to 400 +/- 73 fmol/mg protein; alpha 2A receptor mRNA also increased about 4 fold with no change in abundance of beta actin mRNA. We prepared serum-free conditioned medium (SFCM) from confluent dishes of HT-29 cells and applied this SFCM to cells seeded at low density. A 4.7 fold increase in receptor number was observed in HT-29 cells cultured in SFCM for 3 days and alpha 2A receptor mRNA level increased about 3-fold after 24 h. Dialysis of SFCM against fresh growth medium did not abolish these effects. These results suggest that a substance secreted from HT-29 cells regulates expression of alpha 2A receptors. PMID- 8196493 TI - Corticotropin-releasing hormone (CRH) is a respiratory stimulant in humans: a comparative study of human and ovine CRH. AB - Previous experimental and clinical studies clearly demonstrated that exogenously administered CRH possesses respiratory properties. Until now, these effects were investigated using human (h) CRH in both healthy volunteers and patients under long-term respiration. We now compared the effects of hCRH with those of ovine (o) CRH in ten healthy young males. In particular it should be evaluated whether oCRH with its longer plasma half-life induces a more profound respiratory stimulation. On two separate days within two weeks, ventilation and cardiac performance were measured during steady state conditions by using a computerized cardio-pulmonary exercise testing system. In this placebo controlled double-blind crossover study h- and oCRH (100 ug i.v. each) both augmented minute volume significantly during the observation period. Heart rate also increased after both analogues. All effects were comparable without a significant difference between both substances. There were no major side effects observable. Our data thus demonstrate that both analogues might be suitable for both diagnostic (i.e., testing of respiratory and autonomic responses) and therapeutic purposes. PMID- 8196494 TI - Vascular responsiveness in young, diabetic, and aging hyperinsulinemic rats. AB - The purpose of this study was to compare vascular responsiveness in young (12 week old), aging hyperinsulinemic-glucose intolerant (52 weeks old) and diabetic (streptozotocin; 14 weeks old) rats. Aortic rings with and without endothelium were maintained in organ chambers for isometric tension recording. The contractile response to KCl was significantly enhanced in aortae from diabetic animals when compared to the responses obtained in young and old ones. The contractile response to norepinephrine or U46619, was significantly shifted to the right in the aortae from aging animals, however the aortae from these hyperinsulinemic rats were hyperresponsive to serotonin. Acetylcholine and ADP provoked an endothelium-dependent relaxation which was markedly depressed in the aortae from diabetic animals. The relaxation to ADP was selectively inhibited in the aging animals. The effect of sodium-nitroprusside was not significantly different in the three groups. Isoproterenol and forskolin induced endothelium independent relaxation. Isoproterenol responses were inhibited in aging and diabetic animals, however the forskolin-relaxation was inhibited only in the aortae from aging animals. These results suggest that in two models of diabetes (i.e. Type I insulin-dependent and type II non insulin-dependent) vascular responsiveness is differently affected. Aging hyperinsulinemic animals present a selective hyperresponsiveness to serotonin, a selective dysfunction of ADP induced endothelium-dependent relaxation and smooth muscle adenylate cyclase deficit. In diabetic animals a beta adrenergic hyporesponsiveness, not linked to adenylate-cyclase dysfunction, and non-selective depression of endothelium dependent responses can be observed. PMID- 8196495 TI - Irradiation and responsiveness to pain stimuli in rats. AB - This study evaluates whether irradiation inhibits responses to pain in an animal model. We found that irradiation with doses of 10 Gy, 15 Gy and 17.5 Gy of the lumbar enlargement of the spinal cord inhibits the behavioural responses to the stimulus of the hot-plate. These doses were otherwise without effects. This data is discussed in view of the effects of irradiation of living cells, and we propose that a modification of pain signal processing is accomplished. Similar considerations apply to the human condition. PMID- 8196496 TI - Corticotropin-releasing factor is secreted in the BE(2)-C neuroblastoma cell and is responsive to forskolin. AB - The BE(2)-C human neuroblastoma has been shown to express corticotropin-releasing factor (CRF) messenger RNA. In this study, BE(2)-C cells were treated 5 days with 5 microM retinoic acid. Cell extracts were also applied onto a C18 Vydac column and fractions were assayed for CRF-like immunoreactivity (CRF-LI) which coincided in time of elution with oxidized or non-oxidized CRF synthetic CRF standard. With forskolin treatment, secretion media and cell extract CRF-LI increased in a concentration-dependent fashion. Thus, this cell line synthesizes and secretes CRF and is a good model for studying CRF regulation. PMID- 8196497 TI - Inhibition of macrophage inducible protein expression by delta-9 tetrahydrocannabinol. AB - Macrophages have been shown to undergo a sequential process to full activation in response to priming and triggering signals such as gamma interferon (IFN gamma) and bacterial lipopolysaccharide (LPS). These cells also may be driven directly to full activation by exposure to relatively high concentrations of LPS. Each of the stages to activation is associated with differential protein expression suggesting that newly synthesized proteins are associated with the functional activities attributable to that activation state. These observations indicate that protein profiles may serve as a barometer of the macrophage activation state. Delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana, was shown to inhibit inducible protein expression in response to the priming agents Concanavalin A (Con A) supernatant and IFN gamma. THC also suppressed protein expression in response to LPS. P388D1 and RAW264.7 macrophage like cells, treated with Con A supernatant or IFN gamma, exhibited restructuring of protein profiles based on iso-Dalt two-dimensional gel electrophoresis. Protein profile restructuring, distinctive from that elicited in response to priming agents, was seen for macrophages treated with LPS. Treatment of macrophages with Con A supernatant, IFN gamma, or LPS in concert with THC (10(-7) M to 10(-5) M), resulted in the generation of protein profiles whose patterns reverted approximately to those of unprimed or unactivated macrophages. THC was shown to alter the expression of select proteins whose induction is associated with macrophage priming or activation. The expression of P388D1 macrophage class II Ia molecules of the major histocompatibility complex (MHC), in response to Con A supernatant and IFN gamma, was inhibited. THC also altered the expression of tumor necrosis factor alpha (TNF alpha) elicited by RAW264.7 cells in response to LPS. These results suggest that THC alters macrophage functional activities, at least in part, by suppressing their capacity to express effector molecules elicited in response to priming and activating signals. PMID- 8196498 TI - Structure of a pineal gland-derived antigonadotropic decapeptide. AB - An antigonadotropic decapeptide was extracted from bovine pineal glands, purified by ultrafiltration and Sephadex G-25 gel-filtration chromatography and isolated by serial semi-preparative high performance liquid chromatography. Its primary structure was determined by automated amino acid and microsequence analyses. A synthetic analog of the decapeptide, prepared by solid state methods, was observed to reduce circulating levels of luteinizing hormone and prolactin after intra-atrial injection in male rats. PMID- 8196499 TI - Pertussis toxin normalizes enhanced renovascular responses to angiotensin II in spontaneously hypertensive rats. AB - Previous studies indicate that spontaneously hypertensive rats (SHR) have an exaggerated renal vascular response to angiotensin II (Ang II). Inasmuch as angiotensin receptors are coupled to diverse signalling mechanisms via G proteins, the purpose of this study was to determine whether the enhanced renal vascular response to Ang II in SHR is due to signalling pathways that involve Gi and/or Go. Age-matched SHR and normotensive Wistar-Kyoto rats were administered an intravenous injection of either pertussis toxin (10 micrograms/kg) or vehicle, and 6 days later were prepared for study. Renal vascular responses to Ang II were determined by infusing Ang II into the aorta just above the left renal artery while monitoring renal blood flow and arterial blood pressure. Inhibition of the bradycardic response to N6-cyclopentyladenosine (an adenosine A1 receptor agonist) verified that pertussis toxin interrupted Gi coupled pathways. Renovascular responses to Ang II were significantly greater (p = 0.0009) in vehicle-treated hypertensive rats when compared with vehicle-treated normotensive rats. Pertussis toxin significantly decreased renovascular responses to Ang II in both hypertensive (p < 0.0001) and normotensive (p = 0.0101) rats, but more so in hypertensive rats. In pertussis toxin-treated rats renovascular responses to Ang II were similar in hypertensive versus normotensive rats. CONCLUSIONS: 1) Gi and/or Go contributes importantly to the signalling mechanism through which Ang II affects renal vascular resistance; and, 2) An alteration in the Gi and/or Go mediated signalling pathway in the renal vasculature appears to mediate the enhanced renal vascular response to Ang II in SHR. PMID- 8196501 TI - Prevention of sudden cardiac death by the atypical neuroleptic acepromazine following status epilepticus in rats. AB - Normal male rats in which status epilepticus has been induced by injecting 30 mg/kg of pilocarpine after a single systemic administration of lithium (sufficient to produce blood levels of 0.2 mEq/L) invariably die within 24 hr. Real-time monitoring indicated sudden cardiac death; it was preceded by progressive intensification of arrhythmia. A single systemic injection (25 mg/kg) of the atypical phenothiazine acepromazine prevented the mortality and virtually eliminated the cardiac instability. PMID- 8196500 TI - Role of alpha 1-adrenoceptor subtypes which mediate positive chronotropy in neonatal rat cardiac myocytes. AB - We investigated the involvement of alpha 1-adrenoceptor subtypes in the positive chronotropic response to norepinephrine (NE) in neonatal rat cardiac myocytes at day 3 of culture. The cardiac myocytes at day 3 of culture exhibited a dose dependent positive chronotropic response to NE in the presence of propranolol, a beta-adrenoceptor antagonist. The positive chronotropic responses to NE were completely antagonized by the alpha 1-adrenoceptor antagonist prazosin. The NE induced positive chronotropic response was inhibited 68% by the alpha 1B adrenoceptor antagonist, chloroethylclonidine (CEC), but partially (41%) so by the alpha 1A-adrenoceptor antagonist, WB4101. In the membrane fraction derived from cardiac myocytes at day 3 of culture, pretreatment with CEC decreased the Bmax of the alpha 1-adrenoceptor to 22% of the control value. The NE-induced positive chronotropic response was inhibited 62 and 77% by the voltage-gated Ca2+ channel blocker such as nifedipine and verapamil, respectively. These findings indicate (1) that cultured neonatal rat cardiac myocytes possess both alpha 1 adrenoceptor subtypes, i.e., alpha 1A and alpha 1B, (2) that the predominant alpha 1-adrenoceptor subtypes mediating NE-induced positive chronotropy in neonatal rat cardiac myocytes at day 3 of culture are alpha 1B-subtypes, and (3) that NE-induced positive chronotropy may be caused via voltage-gated Ca2+ channel activation. PMID- 8196502 TI - Mitochondria from Alzheimer's fibroblasts show decreased uptake of calcium and increased sensitivity to free radicals. AB - Many of the biological abnormalities seen in samples of the brain and other tissues from patients with Alzheimer's disease, are consistent with an excessive action of oxygenic free radicals. Mitochondria from fibroblasts grown in tissue culture from skin samples taken at autopsy from patients with histologically confirmed Alzheimer's disease, take up significantly less calcium than do fibroblast mitochondria from age matched non-demented controls. Following exposure to oxygenic free radicals generated by adding ferrous ions to the incubation mixture, calcium uptake is increased to a greater extent in Alzheimer's mitochondria than in controls. At the doses used, pretreatment with the lazaroid antioxidant drug U-74500A, or with the iron chelator deferoxamine, prevents the free radical induced increase in calcium uptake by control mitochondria, but provides only partial protection for Alzheimer's mitochondria. These observations suggest that Alzheimer's fibroblast mitochondria have impaired calcium transport processes and show increased sensitivity to oxygenic free radicals. PMID- 8196503 TI - Role of fatty infiltration during malaria in rhesus monkey. AB - P. cynomolgi B-rhesus monkey model of malarial infection has been used to study lipid infiltration in host tissues in early (exoerythrocytic) and late (chronic) stages of malaria infection. Histochemically we could demonstrate significant infiltration of neutral & total lipids in liver during the exoerythrocytic stage and in liver and kidney in the erythrocytic stage. The parasite used in the study closely resembles the human parasite P. vivax. It has a defined prepatent period, can be cyclically passaged with ease and non fatal in nature. PMID- 8196504 TI - Hypothalamic concentration and release of neuropeptide Y into microdialysates is reduced in anorectic tumor-bearing rats. AB - Hypothalamic concentration of neuropeptide Y was decreased significantly in anorectic tumor-bearing rats, while NPY level was increased significantly in matched carcass weight control rats as compared with freely-feeding controls. In vivo microdialysis of the perifornical hypothalamic area of tumor-bearing rats prior to the development of anorexia revealed no alteration in NPY in dialysates. Following the development of anorexia, however, tumor-bearing rats exhibited significant reduction in NPY concentration in dialysates as compared with either matched carcass weight or freely-feeding control group. These results suggest that hypothalamic NPY concentration and release are decreased selectively in anorectic tumor-bearing rats. Since NPY also elicits less feeding in tumor bearing rats, dysfunction of hypothalamic NPY feeding mechanisms may be of primary importance in cancer anorexia. PMID- 8196505 TI - Comparison of [3H]resiniferatoxin binding to spinal cord and dorsal root ganglia of newborn and adult rats. AB - Capsaicin is frequently used in neurobiological investigations to selectively inhibit response by the primary sensory afferent neurons. The effectiveness of treatment depends significantly on the age of the animals; newborns are both quantitatively and qualitatively more sensitive than adults. In the present study, we used the [3H]resiniferatoxin binding assay to determine whether this different susceptibility to capsaicin between newborns and adult animals may reflect differences either in receptor affinity or density. We report here that whole spinal cord membranes of neonates bound [3H]RTX with similar affinity and positive cooperativity as did the spinal cord membranes from adult animals (Kd values were 24.8 +/- 3.7 and 26.8 +/- 4.8 pM, respectively; Hill coefficients were 2.25 +/- 0.03 and 2.17 +/- 0.05, respectively). However, the receptor density was three-fold higher in the spinal cord membranes of neonates than of adult rats (Bmax values were 142 +/- 13 and 43 +/- 3 fmol/mg protein, respectively). We found no significant difference in the [3H]RTX binding properties of dorsal root ganglia membranes of newborn and adult animals. Our results suggest that a higher density of the vanilloid receptor in the spinal cord (but not in the dorsal root ganglia) of newborn animals may contribute to the quantitative differences between the sensitivity of adult animals and neonates. PMID- 8196506 TI - In vivo labeling of nicotinic cholinergic receptors in brain with [3H]cytisine. AB - [3H]Cytisine was evaluated as an in vivo ligand for the nicotinic cholinergic receptor (nAchR) in mouse brain. The tracer was injected intravenously, and radioactivity in brain regions was analyzed. Radioactivity peaked in the brain at 30 minutes. It was highest in the thalamus, intermediate in the superior colliculi, prefrontal cortex and hippocampus, and low in the cerebellum. Pretreatment with unlabeled cytisine inhibited binding in the thalamus, but not in the cerebellum. Binding was displaced by l-nicotine, but not by d-nicotine or dexetimide. The results suggest that cytisine, appropriately labeled with a positron emitting radionuclide, may be useful for study of nicotinic cholinergic receptors in humans by emission computed tomography. PMID- 8196507 TI - Inhibitory effects of antihypertensive drugs on mesangial cell proliferation after anti-thymocyte serum (ATS)-induced mesangiolysis in spontaneously hypertensive rats. AB - The effects of antihypertensive drugs on mesangial cell proliferation were studied in spontaneously hypertensive rats (SHR) with anti-thymocyte serum (ATS) induced glomerulo-nephritis. Rats were treated with either enalapril (Group 1), nifedipine (Group 2), or reserpine + hydrochlorothiazide + hydralazine (Group 3), or were untreated (Group 4). The animals were sacrificed 2, 4 and 7 days after ATS injection and the glomerular cell number and degree of mesangial area expansion were examined. A marked, similar decrease in glomerular nuclear cell number (NC) due to severe mesangiolysis was observed in all of the groups on day 2. Thereafter, an increase in NC reflecting mesangial cell proliferation after mesangiolysis occurred in Group 4 on days 4 and 7. In Group 1 and 2, the NC was significantly smaller than that in Group 4 on days 4 and 7, indicating suppression of mesangial cell proliferation. In Group 3, however, the number of NCs did not differ from that in Group 4 on days 4 and 7, indicating a lack of such suppression by conventional antihypertensive drugs. The degree of mesangial area expansion (MS) showed the same pattern as mesangial cell proliferation. That is, the rapid increases in MS seen in Group 4 on days 4 and 7 were apparently suppressed in Groups 1 and 2, but not in Group 3. Our in vivo observations that both an angiotensin converting enzyme (ACE) inhibitor and a calcium channel blocker suppress mesangial cell proliferation and mesangial area expansion suggest that these agents have practical implications in the treatment of mesangial proliferative glomerular diseases through the suppression of excess mesangial cell proliferation. PMID- 8196508 TI - Renal endothelin mechanism in altered thyroid states. AB - Endothelin (ET) mechanisms were studied in hyper- and hypo-thyroid states in rats. Hyperthyroidism was induced by daily administration of thyroxine (0.1 mg/kg, i.p.) for 8 weeks, while hypothyroidism was induced by daily administration of methimazole (10 mg/kg, i.p.) for 8 weeks. The concentration of endogenous ET-1 was determined in the kidneys using radioimmunoassay. Systemic hemodynamics and renal blood circulation was measured using a radioactive microsphere technique. A significant increase in systolic and diastolic blood pressure, heart rate and cardiac output was observed in hyperthyroid rats as compared to eu- and hypo-thyroid rats. Total peripheral resistance was found to be similar in eu-, hyper- and hypo-thyroid rats. The endogenous concentration of ET-1 in the kidneys was significantly lower in hyper- as compared to eu- and hypo thyroid rats. The blood flow to the kidneys was significantly increased in hyper- as compared to eu- and hypo-thyroid rats. Infusion of ET-1 (100 ng/kg/min i.v. for 45 min) produced a significant decrease in blood flow to the kidneys of eu-, hyper- and hypo-thyroid rats. The decrease in blood flow was similar in eu-, hyper- and hypo-thyroid rats, indicating that the response of renal blood vessels to exogenous ET-1 is not altered during thyroid dysfunction. Since endogenous ET 1 is involved in the regulation of vascular tone, it may be concluded that in hyper-thyroid rats decrease in concentration of the renal ET-1 could be contributing to an increase in blood flow to the kidney. PMID- 8196509 TI - Vasoactive intestinal peptide inhibits fMLP-induced respiratory burst in human lymphocytes. AB - N-Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) induced in lymphocytes the production of reactive oxygen intermediates in a process which was inhibited by the presence of Vasoactive Intestinal Peptide (VIP) in a dose-dependent response at VIP concentrations in the range 10(-10)-10(-7) M. The dissociation constant for the high-affinity receptors of VIP agrees with the ID50 of the activation of adenylate cyclase which are close to 0.2 nM VIP, whereas the ID50 for the inhibition by VIP of fMLP-induced chemiluminescence approaches to 5 nM VIP. Both IBMX and Forskolin produced in lymphocytes an inhibition of fMLP-induced chemiluminescence. The degree of inhibition was ascertained to be additive in the presence of the above indicated agents and suboptimal concentrations of VIP. The saturation by cAMP of its putative target, the regulatory subunit of protein kinase A, appears to be required for the onset of the inhibitory effect of VIP. This study provides evidence of the molecular signal, namely cAMP, which provokes an inhibitory effect on chemoatractant-stimulated human lymphocytes and further support a role for VIP as a mediator in the neuroimmune system. PMID- 8196510 TI - Effect of streptozotocin-induced diabetes on somatostatin receptors in the anterior pituitary, hypothalamus and cerebral cortex of the male rat. AB - In order to better understand the mechanisms underlying the reduction in GH secretion in diabetic rats, we have characterized and measured SRIH receptors in the hypothalamus and anterior pituitary gland 5 and 9 days after induction of diabetes in the rat. Experimental diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg/kg. Basal plasma GH was significantly reduced in diabetic rats. Chronic insulin replacement therapy partly restored plasma GH and blood glucose levels in these animals. A significant reduction in SRIH receptor concentrations was demonstrated in the hypothalamus and anterior pituitary gland, 5- and 9- days after STZ injection. These changes were not significantly corrected by insulin replacement. Cerebral cortex SRIH receptor concentrations were unaffected by experimental diabetes. We conclude that hypothalamic and pituitary SRIH receptor levels are lowered in diabetic rats. These changes may contribute to aberrant GH secretion in diabetes and they indicate that pituitary sensitivity to exogenous somatostatin should be tested in diabetic patients. PMID- 8196511 TI - Acetylsalicylate (ASA)-induced mitochondrial dysfunction and its potentiation by Ca2+. AB - Although it has been suggested that acetylsalicylate (ASA)-induced mitochondrial dysfunction plays an important role in the pathogenesis of Reye's syndrome, administration of ASA alone does not cause this syndrome in therapeutic doses. We noted, however, that Ca2+ plays important roles in the regulation of cellular functions. ASA at concentrations of 250 microM or less, which had little effect on succinate-linked respiration, impaired Ca2+ accumulation in liver mitochondria by causing an increase in Ca2+ release. ASA plus Ca2+, which in concentrations of 150 microM or less alone had little effect on mitochondrial respiration, inhibited state 3 respiration and dinitrophenol-induced uncoupling of respiration. In addition, ASA plus Ca2+ increased state 4 respiration and ATPase activity. These results indicate that ASA plus Ca2+ impaired mitochondrial ATP synthesis, and suggest that ASA and ASA-induced Ca2+ increases in cytosol form a vicious circle of effects. Furthermore, oral administration of ASA (150 mg/kg for 5 days running) to rats did not affect mitochondrial structure or liver function, but resulted in aberrations of mitochondrial respiration. These results suggest that even therapeutic doses of ASA may induce alteration in mitochondrial function. PMID- 8196512 TI - HBcAg and HBsAg expression in ductular cells in chronic hepatitis B. AB - The possible involvement of bile duct epithelium (BDE) in chronic hepatitis B was examined by immunohistochemical investigation of HBcAg and HBsAg expression in biliary cells in 47 liver biopsies with both viral antigens detectable in hepatocytes. HBcAg- and HBsAg-positive cells were identified in nine and five cases, respectively, in atypical and occasionally in typical ductules in cases of acute exacerbation, chronic active hepatitis and active cirrhosis. Atypical ductules were usually located in areas of periportal fibrosis and in cirrhotic septa. Liver cell plates expressing viral markers and undergoing ductular transformation (positive reaction of hepatocytes to BDE-specific, wide-spectrum keratin) were also observed in acinar zone 1, at the periphery and within parenchymal nodules in a number of cases. The presence of both viral antigens in atypical ductules in cases of advanced chronic liver disease most probably expresses the persistence of the virus in cells deriving from biliary metaplasia of infected hepatocytes. However, the detection of the virus in a few typical ductules is indicative of a direct viral infection. According to these findings, ductular cells seem to serve as a suitable host for HBV, their genotype permitting viral replication and antigen production. PMID- 8196513 TI - Phenotypic change in portal fibroblasts in biliary fibrosis. AB - Portal fibroblasts have been considered responsible for biliary fibrosis. Since lipocytes show differentiation toward myofibroblast-like cells in hepatic fibrogenesis, we studied whether similar differentiation of portal fibroblasts could be observed in biliary fibrosis. We examined rat livers after bile duct ligation by double immunofluorescent staining of alpha-smooth-muscle actin (alpha smA) and desmin and also by electronmicroscopy. In the portal tract of normal livers, alpha-smA-positive cells were noted only in the vessel wall, whereas desmin-positive cells were occasionally seen in the connective tissue as well. With the development of biliary fibrosis, alpha-smA was remarkably expressed in the portal connective tissue, while desmin was seen in a small portion of alpha smA-positive cells around proliferating bile ducts. In normal livers, portal fibroblasts presented quiescent features, such as a small Golgi complex and a few cisternal profiles of endoplasmic reticulum under electron microscopy. After 7 days of bile duct ligation, portal fibroblasts proliferated, were arrayed in multilayers, and were associated with collagen bundles. Some of these fibroblasts had numerous cytoskeletal components, and developed rough endoplasmic reticulum and a dense body. These data suggest that portal fibroblasts appear to differentiate toward myofibroblasts in biliary fibrosis. PMID- 8196514 TI - Diclofenac-induced hepatitis: case report and literature review. AB - A case of diclofenac-induced hepatitis, in a 53-year-old Indian woman with recurrent jaundice, is presented. The diagnosis was suspected from the appearance of the liver biopsy and was confirmed by the temporal association with drug usage and cure on withdrawal of the drug. PMID- 8196515 TI - The arterial blood ketone body ratio as a possible marker of multi-organ failure in patients with alcoholic hepatitis. AB - The arterial blood ketone body ratio (AKBR: acetoacetate/3-hydroxybutyrate) within 48 h of admission is reported to be an excellent prognostic indicator for acute hepatic failure. In this study, we assessed the AKBR in 63 patients receiving supportive medical therapy for alcoholic hepatitis, in order to investigate its efficacy for predicting complications and the prognosis. Twelve patients (19%) died and 51 patients (81%) survived. Hepatic encephalopathy, severe coagulopathy, and renal failure were the critical complications (P < 0.01), and the AKBR at 72 h of hospitalization was closely correlated with these complications (P < 0.01), although they could not be predicted in any other way during the early admission period. The AKBR of normal individuals ranged from 1.0 to 2.1 (1.54 +/- 0.26, mean +/- SD), so an AKBR > 1.0 (mean-2SD) was defined as normal. The AKBR value at 48 and 72 h of hospitalization showed a significant difference between survivors and non-survivors (P < 0.01). All survivors showed an increase of the AKBR to above 0.7 at 72 h, with subsequent maintenance of the ratio over 1.0, while eight of the 12 non-survivors had sustained suppression of the AKBR below 0.7 at 72 h. Seven of these eight patients subsequently developed multiple organ failure. These findings suggest that the AKBR could be a possible marker of potentially fatal complications and a poor prognosis in patients with alcoholic hepatitis. PMID- 8196516 TI - Immunohistochemical and ultrastructural study of hepatic sinusoidal linings during dichloropropanol-induced acute hepatic necrosis. AB - An acute phase of severe hepatic necrosis induced by dichloropropanol was examined immunohistochemically and ultrastructurally, in order to study chronological changes of sinusoidal morphology during acute hepatic injury. Male Wistar rats were injected with 1,3-dichloro-2-propanol (DC2P) and sacrificed at various intervals after the injections. DC2P-injected rats showed zonal necrosis of the centrilobular space with a peak from 24 to 48 h after the injection. Destruction of sinusoidal linings appeared at 4 h, and was gradually aggravated along the advancing hepatocytic necrosis. Monocytic influx into the necrotic areas was initiated at 6 h. At 48 h, collapsed centrilobular spaces showed a loss of most sinusoidal structures with active phagocytosis of macrophages, proliferation of perisinusoidal cells, and accumulation of collagen fibrils. At 72 h, there were many regenerating sinusoidal structures, which were composed of rather thick and less fenestrated endothelium and underlying multilayered processes of mesenchymal cells, along the regenerating hepatocytes. In these areas, occasional junctions between regenerating hepatocytes and mesenchymal cells were seen. Reconstruction of sinusoidal linings was closely related to the hepatocytic regeneration, and a hepatocytic-mesenchymal interaction might participate in this morphodynamic course of the sinusoidal reconstruction. PMID- 8196517 TI - [Antimalaria vaccines: where does the research stand?]. PMID- 8196518 TI - [Madagascar: current public health situation]. PMID- 8196520 TI - [Pharmaceutical innovation and the eradication of diseases]. PMID- 8196519 TI - [Pink eye in the tropics]. PMID- 8196521 TI - [Chronicle of a failure: cholera]. PMID- 8196522 TI - [In vitro production of specific antibodies: preliminary results]. AB - In vitro production of specific antibodies or IVPA is a technique that involves isolating mononuclear cells from blood, placing them in culture, and detecting antibodies in the culture supernatant. The presence of antibodies confirms active production by B lymphocytes and is proof of ongoing infection. To validate this technique for routine laboratory use, we tested 16 subjects: 11 for toxoplasmosis and cytomegalovirus and 5 for viral hepatitis type A or B. The results obtained using IVPA were compared with those obtained using conventional serologic methods. IVPA documented IgM for cytomegalovirus in the only subject in whom serology showed IgM for that virus. The test was also positive in 2 subjects undergoing vaccination for viral hepatitis type B and suffering from acute viral hepatitis type A. These concordant results demonstrate that IVPA is a valuable adjuvant technique for diagnosis of ongoing infection especially insofar as it avoids the need for antibody kinetic studies or isolation of the virus. It also provides a simpler and less expensive alternative to gene amplification and cell culture. PMID- 8196523 TI - [Delayed hypersensitivity after anthrax vaccination. I--Study of guinea pigs vaccinated against anthrax]. AB - To evaluate delayed hypersensitivity after anthrax vaccination, an Anthraxin skin test was performed in 682 guinea pigs at various times after immunization with veterinary unencapsulated active anthrax vaccine. Results were compared with those obtained in unimmunized control guinea pigs (n = 216), in guinea pigs that received a non-immunizing dose of live vaccine (n = 183) and in guinea pigs inoculated with inactivated vaccine (n = 120). Anthraxin skin tests were positive in the first postvaccination days. The incidence and intensity of positive tests peaked between two weeks and one month after vaccination and then gradually decreased during the first year. Study of resistance of guinea pigs to an inoculum at a lethal dose of a virulent strain of Bacillus anthracis showed a close correlation between positive tests and resistance. These findings demonstrate development of cell-mediated immunity after anthrax vaccination. The Anthraxin skin test should have practical applications for the production of vaccines and for evaluation of the immune status of vaccinated livestock [corrected]. PMID- 8196524 TI - [Coxofemoral pathology in rheumatology consultation in Togo]. AB - A retrospective study was conducted to determine the relative incidence and characteristics of the different forms of coxofemoral disease encountered in a hospital rheumatology clinic in Lome (Togo). Hemoglobin electrophoresis was performed in all subjects included in the study. Of 2812 subjects examined over a 44-month period, 80, i.e. 2.8%, presented clinically and radiologically documented coxofemoral disease. Necrosis of the femoral head was the cause of coxofemoral disease in 36 subjects i.e. 45%, and was the most frequent etiology. In these 36 subjects hemoglobin was normal in 5 cases, type AS in 5, type AC in 1, type SS in 9, and type SC in 16. Coxarthrosis was detected in 31 subjects: either primary (n = 20) or secondary (n = 11). In this group, hemoglobin was normal in all but 3 subjects who exhibited type AS. The other etiologies observed were coxitis (n = 20) and epiphysitis (n = 3). This study documents the major role of hemoglobinopathy in the pathogenesis of coxofemoral disease in Black Africa. It confirms that AS and SC heterozygoses are not involved in the onset of aseptic necrosis. PMID- 8196525 TI - [Clinical and hematological profile of Lepore Hemoglobin in Ivory Coast]. AB - Out of 97320 hemoglobin electrophoreses performed in Abidjan between January 1976 and January 1991, all subjects with hemoglobin Lepore were isolated. This trait was identified by three techniques, i.e., alkaline pH electrophoresis, acid pH electrophoresis, and isoelectric focusing. Seventy-nine cases of hemoglobin Lepore were observed. All were heterozygotes with type HbA-Lepore (n = 54), HbC Lepore (n = 8) or HbS Lepore (n = 17). Where heterozygosis A and C had clinically silent, heterozygosis Hb-S Lepore resulted in a moderate chronic hemolytic anemia and, in all cases, painful episodes similar to those observed during homozygote sickle-cell disease. However the onset of episodes was later and their occurrence was less frequent. On hemograms, the Lepore trait (HbA Lepore) appeared as a pseudo-polyglobulia with microcytosis; similar features were observed for heterozygosis HbC Lepore. Heterozygosis HbS Lepore caused moderate anemia (mean hemoglobin level: 10.66 g/dl) and microcytosis (MGV = 68.8 fl). The characteristics show that the clinical and hematological behavior of hemoglobin Lepore, a rare hemoglobin, is similar to heterozygous beta-thalassemia. PMID- 8196526 TI - [Sickle cell disease and depression: preliminary study using the Hamilton rating scale for depression]. AB - Prolonged latency in the appearance of REM sleep as a marker of depression has been demonstrated in patients with the sickle-cell disease. To detect the possible existence of depressive disturbances in patients with sickle-cell disease, the Hamilton rating scale for depression (17 items) was used in 30 patients with homozygote sickle-cell disease and 31 carriers of the sickle-cell trait, treated or not with vasodilator drugs. None of the 61 subjects studied presented a score of 18 or more on the Hamilton rating scale, this being the threshold value for confirming the existence of moderate depression. However, analysis of variance showed an increase in mental dullness, agitation and somatization disorder. Dullness was related to the extent of anemia and the number of sickle-cell crises per year. Treatment had an effect on agitation in patients, with pentoxyfylline having a soothing effect unlike cinepazide maleate. Women complained of insomnia in the middle of the night and somatic anxiety and presented higher total scores than men. Men exhibited a higher degree of mental dullness. The findings of this preliminary study indicate that while not associated with frank depression, the sickle-cell gene has psychological repercussions on various depressive parameters and that these patients can benefit from treatment with pentoxyfylline. PMID- 8196527 TI - [Ecology of Cryptococcus neoformans in central Africa]. AB - Cryptococcosis associated with AIDS is mainly due to Cryptococcus neoformans var. neoformans which is found in saprophytic form in pigeon droppings. This variety has been isolated in Central Africa, particularly in Zaire, Burundi and Rwanda, from dust collected from the houses of patients with cryptococcosis. Several patients confirmed frequent contact with pigeons. Recent studies in Australia demonstrated a link between the yeast and Eucalyptus of the camaldulensis and teriticornis species. These two species were imported to Central Africa from Australia. Examination of 657 Eucalyptus specimens collected in Rwanda did not detect the yeast in any type of tree. This finding casts doubt on the role of Eucalyptus in the ecology of cryptococcosis in Central Africa. PMID- 8196528 TI - [Value of bony resection-reconstruction by avascular autologous fibular graft in the tropical milieu. Treatment of a giant cavernous hemangioma of the humerus]. AB - In a poorly equipped tropical setting, limb amputation is often considered as the only therapeutic solution for malignant tumors or large benign tumors. However it can be avoided by bone replacement using an avascular autologous fibular graft. This method was used in a young girl from Tchad presenting a giant cavernous hemangioma of the humerus. This technique allowed salvage of the extremity but resulted inevitably in radial paralysis. The time needed for bone healing was normal. This technique required minimum facilities and was perfectly biocompatible. It can be used in tropical settings where allograft techniques and prosthetic replacement are not available. PMID- 8196529 TI - [Osteogenesis imperfecta in monozygotic twins in Burundi]. AB - Little data is available about osteogenesis imperfecta in Black African children. This defect was diagnosed in monozygotic twins from Rwanda who presented multiple fractures, in particular of the femur, when they began to walk. Osteogenesis imperfecta was confirmed by lower limb deformity, presence of wormian bones in the skull, blue sclera, and tooth defects. In addition to the fact that it is uncommon to encounter this condition in monozygotic twins, this case is interesting for several reasons. Was osteogenesis imperfecta in these patients type I, frequent, or type III, exceptional? More importantly, this case stresses the high prevalence of type III in Black Africa which could constitute a hot-bed in the world. PMID- 8196530 TI - [Value of pedicled myoplasty in the treatment of severe mediastinitis. A case report]. AB - Sternotomy is the approach of choice for cardiac surgery. Mediastinitis is a rare complication of median sternotomy with high morbidity and mortality. We describe a case of severe mediastinitis occurring after median sternotomy performed in a patient presenting diving goiter. Two-stage irrigation/drainage was unsuccessful. This failure led to opening of the chest and coverage with a pediculated flap using the grand pectoralis muscle. This stratagem allowed complete healing. This case provides an opportunity to discuss the different surgical techniques used to treat severe mediastinitis and to emphasize the value of muscle flaps in the management of recalcitrant median sternotomy wounds. PMID- 8196531 TI - [Tuberculosis at the time of AIDS in sub-Saharan Africa. Experience in a central African country: Burundi]. PMID- 8196532 TI - [Epidemiological, clinical, and microbiological characteristics of the new strain Vibrio cholerae 0139]. PMID- 8196533 TI - [Somalia: the French army and humanitarian medical aid]. PMID- 8196534 TI - [Central African Republic: management by hospital consultation of patients with sexually transmitted diseases]. PMID- 8196535 TI - [Amebic liver abscess with ultrasonographic pseudo-tumor aspects]. PMID- 8196536 TI - [Gonorrhea, arthritis, and gonococcal arthritis. Experience in a semi-urban zone of Central African Republic]. PMID- 8196537 TI - [Frequency of atherosclerosis observed in medico-legal autopsies in Niger]. PMID- 8196538 TI - [Meningococcal meningitis A in Africa. Findings underline the value of vaccinal prophylaxis for the traveller]. PMID- 8196539 TI - [Value of early external version maneuver in developing countries]. PMID- 8196540 TI - IpaB mediates macrophage apoptosis induced by Shigella flexneri. AB - Shigella flexneri kills macrophages through apoptosis, involving the induction of host cell DNA fragmentation and characteristic morphological changes. Shigella can only cause damage if it escapes from the phagolysosome into the cytoplasm. The S. flexneri cytotoxic genes have been localized to the ipa operon of shigella's virulence plasmid. ipaB, C and D deletion mutants are not invasive and therefore not cytotoxic. In order to distinguish genes involved in the escape from the phagolysosome as distinct from cytotoxicity, we constructed Shigella strains that secrete low amounts of Escherichia coli haemolysin (hly(low)). These strains can escape into the cytoplasm of the macrophage even in the absence of the invasion plasmid as verified by electron microscopy and resistance to chloroquine. Macrophages were infected with different ipa mutants expressing hly(low). Both delta ipaC hly(low) and delta ipaD hly(low) were cytotoxic whilst delta ipaB hly(low) and a hly(low) strain cured of shigella's pathogenicity plasmid were not. Furthermore, both delta ipaC hly(low) and delta ipaD hly(low) killed through apoptosis as shown by both changes in ultrastructural morphology and fragmentation of the host cell DNA. These results demonstrate that ipaB is essential for S. flexneri to induce apoptosis in macrophages. PMID- 8196541 TI - Mutagenesis of Legionella pneumophila using Tn903 dlllacZ: identification of a growth-phase-regulated pigmentation gene. AB - Study of the molecular basis for Legionella pneumophila pathogenicity would be facilitated with an efficient mutagen that can not only mark genomic mutations, but can also be used to reflect gene expression during macrophage infection. A derivative of Tn903, Tn903dlllacZ, is shown to transpose with high efficiency in L. pneumophila. Tn903dlllacZ encodes resistance to kanamycin (KmR) and carries a 5' truncated 'lacZ gene that can form translational fusions to L. pneumophila genes upon transposition. The cis-acting Tn903 transposase is supplied outside Tn903dlllacZ, and hence chromosomally integrated copies are stable. KmR LacZ+ insertion mutants of L. pneumophila were isolated and shown by DNA hybridization to carry a single Tn903dlllacZ inserted within their chromosomes at various locations. One particular KmR LacZ+ mutant, AB1156, does not produce the brown pigment (Pig-) characteristic of Legionella species. Tn903dlllacZ is responsible for this phenotype since reintroduction of the transposon-linked mutation into a wild-type background results in a Pig- phenotype. L. pneumophila pigment production is normally observed in stationary-phase growth of cells in culture, and beta-galactosidase activity measured from the pig::lacZ fusion increased during the logarithmic-phase growth and peaked at the onset of stationary phase. Interestingly, pig::lacZ expression also increased during macrophage infection. The pigment itself, however, does not appear to be required for L. pneumophila to grow within or kill host macrophages. PMID- 8196542 TI - The identification of rofA, a positive-acting regulatory component of prtF expression: use of an m gamma delta-based shuttle mutagenesis strategy in Streptococcus pyogenes. AB - Binding of the Gram-positive pathogenic bacterium Streptococcus pyogenes (group A streptococcus) to respiratory epithelium is mediated by the fibronectin-binding adhesin, protein F. Most strains of streptococci regulate the expression of protein F in response to oxygen levels and redox potential; however, JRS4 constitutively binds high levels of fibronectin under all environmental conditions. In this study, we have examined the regulation of protein F expression in JRS4 using a shuttle mutagenesis strategy novel to S. pyogenes. Cloned DNA representing the chromosomal loci adjacent to the gene which encodes protein F (prtF) was subjected to transposon mutagenesis in Escherichia coli using a derivative of transposon m gamma delta that was modified to contain a streptococcal antibiotic-resistance gene. mutagenized DNA was then returned to the streptococcal chromosome by allelic replacement. Analysis of the resulting fibronectin-binding phenotypes revealed that insertions in a region upstream of prtF abolished the constitutive phenotype. However, these mutants now demonstrated regulation in response to both oxygen levels and redox potential. Because these insertions define a locus responsible for the constitutive phenotype, it has been designated rofA (regulator of F). Chromosomal interruption studies using integrational plasmids together with complementation data from a previous study (VanHeyningen et al., 1993) suggested that rofA acts as a positive trans-acting regulator of prtF. Construction of prtF-lacZ fusions indicated that transcription of prtF is constitutive in JRS4 but is regulated in rofA mutants. Analysis of the DNA sequence defined by the rofA insertions revealed a 1495 bp open reading frame, whose predicted product (RofA) possessed both a putative helix-turn-helix motif and limited homology to two other transcriptional activators (Mry, PrgR) of Gram-positive surface proteins. Sequences homologous to rofA were found in regulated strains of S. pyogenes, which suggests that rofA may act as an activator of prtF in response to an unidentified environmental signal. We speculate that the allele reported here contains a mutation that renders it constitutively active. PMID- 8196543 TI - Molecular cloning and sequence of comK, a gene required for genetic competence in Bacillus subtilis. AB - The transformation-deficient strain E26, isolated as a pHV60 insertion mutant, was used to isolate comK, a novel transcription unit required for genetic competence in Bacillus subtilis. Mutational analysis and sequence determination showed that comK contained one open reading frame (ORF), which could encode a protein of 192 amino acid residues with a predicted molecular weight of 22,500. An integrated copy of comK not only complemented the competence deficiency of a comK deletion mutant, but also that of strains E26 and FB93. Expression of comK occurred exclusively in glucose-based minimal medium during the transition to stationary growth phase. Furthermore, the expression of late competence genes appeared to be dependent on the gene product of comK, the expression of which in turn depended on the presence of a functional comL (or srfA) transcription unit. These epistatic interactions indicate that comK is a competence locus occupying an intermediate position in the competence signal transduction network. Primer extension analysis showed that comK has one major transcription start site, preceded by a sequence resembling the consensus promoter used by the sigma A form of RNA polymerase. PMID- 8196544 TI - Identification and cloning of a fur homologue from Neisseria meningitidis. AB - The iron response in a number of bacterial systems is mediated by fur (ferric uptake regulation)-like regulatory systems. We have cloned and characterized a gene from Neisseria meningitidis that was homologous to Escherichia coli fur. This clone was capable of modulating expression from both E. coli and neisserial iron-regulated promoters in response to iron, and it produced a protein that reacted with anti-E. coli fur serum. Although the DNA and predicted amino acid sequences were very similar to those of four other published fur homologues, meningococcal fur was the most divergent of the group. Inability to construct a meningococcal fur mutant suggested that fur may be essential in this species. PMID- 8196545 TI - Isolation and characterization of IS31831, a transposable element from Corynebacterium glutamicum. AB - A transposable element from a coryneform bacterium, Corynebacterium glutamicum ATCC 31831 was isolated and characterized. The element IS31831 is a 1453 bp insertion sequence with 24 bp imperfect terminal inverted repeats. It contains one open reading frame highly homologous at the amino acid level to the transposase of IS1096 from Mycobacterium smegmatis. Both IS31831 and IS1096 exhibit several common characteristics suggesting that they constitute a new family of insertion sequences. IS31831 was isolated by taking advantage of the sucrose sensitivity of coryneform bacteria conferred by expression of the Bacillus subtilis sacB gene. An Escherichia coli/Corynebacterium shuttle vector useful for the isolation of transposable elements from the coryneform group of bacteria was constructed. PMID- 8196546 TI - The cellulose-binding domain of endoglucanase A (CenA) from Cellulomonas fimi: evidence for the involvement of tryptophan residues in binding. AB - Cellulomonas fimi endo-beta-1,4-glucanase A (CenA) contains a discrete N-terminal cellulose-binding domain (CBDCenA). Related CBDs occur in at least 16 bacterial glycanases and are characterized by four highly conserved Trp residues, two of which correspond to W14 and W68 of CBDCenA. The adsorption of CBDCenA to crystalline cellulose was compared with that of two Trp mutants (W14A and W68A). The affinities of the mutant CBDs for cellulose were reduced by approximately 50- and 30-fold, respectively, relative to the wild type. Physical measurements indicated that the mutant CBDs fold normally. Fluorescence data indicated that W14 and W68 were exposed on the CBD, consistent with their participation in binding to cellobiosyl residues on the cellulose surface. PMID- 8196547 TI - Molecular analysis of RepHI1A, a minimal replicon of the IncHI1 plasmid R27. AB - R27, a large conjugative plasmid of the HI incompatibility group, was subjected to a subcloning analysis which revealed the presence of a Poll-independent replicon and determinants contributing to incompatibility within a 2.7 kb SalI/XbaI fragment. The DNA sequence of the minimal replicon revealed the presence of a large open reading frame (ORF) as well two sets of 19 bp repeated oligonucleotides (iterons), in addition to characteristic Escherichia coli origin elements. The protein encoded by the ORF possesses homology with replication initiator proteins encoded by a number of plasmids from different incompatibility groups. Deletion analysis suggested that the iterons are responsible for incompatibility reactions. Dissection of the replicon confirmed this and defined a minimal origin of 230 bp. The putative replication initiator was expressed in an in vitro transcription-translation system, and the 5' end of the mRNA encoding its synthesis was identified. Transcriptional fusion of the repA promoter to lacZ demonstrated an autoregulatory function of RepA. A series of iterons present downstream of the RepA coding sequence are dispensable but are responsible for copy-number control. The minimal replicon appears to be partition-defective. PMID- 8196548 TI - Regulation of the permeability of the gonococcal cell envelope by the mtr system. AB - The mtrR gene of Neisseria gonorrhoeae controls the level of susceptibility to hydrophobic antibiotics and detergents. The mtrR gene was cloned and shown to encode a putative transcriptional repressor. The mtr region was homologous to the envCD and acrAB regions of Escherichia coli, which are also involved in susceptibility to hydrophobic compounds. A homologous repressor protein was encoded by a previously unrecognized open reading frame within both the envCD and acrAB regions. Deletion of mtrR resulted in increased resistance to antibiotics and detergents: the mtrR mutations in two penicillin-resistant clinical isolates resulted in a change of His-105 to Tyr. We propose that the mtrR repressor allows gonococci to regulate the permeability of its cell envelope in response to environmental signals, so that they can grow in the presence of toxic faecal lipids in the rectum as well as in the genital tract. PMID- 8196549 TI - An ABC-transporter from Streptomyces longisporoflavus confers resistance to the polyether-ionophore antibiotic tetronasin. AB - Streptomyces longisporoflavus produces the polyketide-polyether antibiotic, tetronasin, which acts as an ionophore and depolarizes the membrane of bacteria sensitive to the drug. A genomic library of S. longisporoflavus DNA was cloned in Streptomyces lividans and screened to identify tetronasin-resistance determinants. The inclusion of 0.2M NaCl in the growth medium with tetronasin markedly improved the sensitivity of the screen. Two different resistance determinants, designated tnrB (ptetR51) and tnrA (ptetR11) respectively, were identified. The determinant tnrB (ptetR51) but not tnrA (ptetR11), also conferred resistance to tetronasin when cloned into Streptomyces albus. The tnrB determinant was further localized, by subcloning, to a 2.8 kb KpnI fragment. DNA sequence analysis of this insert revealed one incomplete and two complete open reading frames (ORFs 1, 2 and 3). The deduced sequence of the gene product of ORF2 (TnrB2) revealed significant similarity to the ATP-binding domains of the ABC (ATP binding cassette) superfamily of transport-related proteins. The adjacent gene, ORF3, is translationally coupled to ORF2 and would encode a hydrophobic protein (TnrB3) with six transmembrane helices which probably constitutes the integral membrane component of the transporter. The mechanism of tetronasin resistance mediated by tnrB is probably an ATP-dependent efflux system. PMID- 8196550 TI - Entamoeba histolytica: electron-dense granule secretion, collagenase activity and virulence are altered in the cytoskeleton mutant BG-3. AB - HM-1:IMSS, a pathogenic strain of Entamoeba histolytica, and its mutant BG-3, identified by resistance to cytochalasin D, were tested for their capacity to: (i) secrete electron-dense granules; (ii) adhere and digest native type I collagen gels; and (iii) produce liver abscesses in new-born hamsters. The results demonstrate that the mutant has low adherence to collagen, low electron dense granule secretion and collagenolytic activity, and low capacity to produce liver lesions in vivo, compared with the parental strain HM1:IMSS. PMID- 8196551 TI - Nodulation protein NodL of Rhizobium leguminosarum O-acetylates lipo oligosaccharides, chitin fragments and N-acetylglucosamine in vitro. AB - Upon induction of their nodulation genes, the root nodule-inducing Rhizobium bacteria produce lipo-oligosaccharide signal molecules. All lipo-oligosaccharides identified from Rhizobium leguminosarum bv. viciae carry an O-acetyl group at the C-6 position of the non-reducing terminal sugar, the presence of which is important for biological activity and host specificity. Previously we showed that a functional nodL gene product is required for the presence of this O-acetyl moiety. The production of polyclonal antibodies against isolated NodL protein, using a NodL-overproducing Escherichia coli strain is described. These antibodies were used (i) to elucidate the subcellular localization of the NodL protein, which appeared to be present in the cytosol, and (ii) for the purification of native NodL protein from E. coli. Here we provide biochemical proof that purified NodL protein has transacetylating activity in vitro with acetyl-CoA as the acetyl donor. NodL protein appeared to be able to acetylate various substrates, such as lipo-oligosaccharides, chitin fragments and N-acetylglucosamine. For chitinpentaose as the substrate we have shown, using mass spectrometry and NMR spectroscopy, that NodL protein substitutes one O-acetyl group at the C-6 position of the non-reducing terminal sugar. PMID- 8196552 TI - Alcoholic liver disease may be prevented with adequate nutrients. AB - Alcoholic liver disease is the result of a synergism between ethanol and nutritional factors. Therefore, it follows that the pathogenesis of alcoholic liver disease may be affected by the regulation of the intake of nutrients as well as by the regulation of the intake of ethanol. PMID- 8196553 TI - SIDS and chaos. AB - Sudden Infant Death Syndrome may exhibit chaotic behavior because it fits common characteristics of chaotic systems including unpredictability, sensitivity to initial conditions, dependence on parameters, and coupling. Chaos theory suggests that preventive efforts should be added to those directed toward a 'cure'. PMID- 8196554 TI - The shortening of the photoperiod may alter gene expression in winter depression. AB - Winter depression is characterised by recurrent major depressive episodes with a seasonal (winter) pattern. Reduced exposure to daylight due to shortening of the day has been hypothesized to trigger off the onset of a depressive episode. Daily exposures to light during the dark period have been used as the treatment of choice for winter depression. A genetic predisposition for high responsiveness to light is thought to exist in patients with winter depression. Altered gene expression may contribute to the unique sensitivity and mediate the antidepressant effects of light. PMID- 8196555 TI - Diabetes can be prevented by reducing insulin production. AB - Hypersecretion of insulin increases the chance of the incidence of diabetes type I and II, while inhibiting insulin secretion helps prevent diabetes. Trace elements like zinc and vanadium prevent hyperinsulinemia, partly because of their own insulin activity, which is also a property of interleukin-1 (IL-1), particularly during periods of illness and stress. Like vanadium, IL-1 can replace insulin for many hours and regulate glucose metabolism. Vanadium, zinc and IL-1 ensure that insulin-producing beta-cells in the pancreas do not lose too much zinc, which leaves the beta-cells together with insulin. Zinc forms a complex with metallothionein in beta-cells that provides protection against free (oxygen) radicals, which become active during immune responses triggered by bacteria and viruses, for instance. In addition, zinc is the only non-toxic trace element in the body that regulates concentration-dependent immune responses on many levels. Avoiding deficiencies of trace elements will enable the reduction of the incidence of diabetes. PMID- 8196556 TI - Snoring may be linked to culture. AB - The estimates of the incidence of snoring in adults that have been provided by four epidemiological studies vary from 16-89% of the population. Collectively, these data are completely confounded by country of origin and thus may reflect cultural differences that contribute to snoring. While the etiology of snoring is not fully known, speculation has focused on gender and age as primary factors that contribute to this behavior. Within the limitations imposed by the designs of these four studies, we compared the relative strength of the relationships between snoring and gender, age, and culture. These analyses suggest that certain variables associated with cultures appear to be more salient than both gender and age, as determinants of snoring. PMID- 8196557 TI - Hypothesis--pouchitis represents a useful clinical model of ulcerative colitis. AB - Various mechanisms have been proposed for the aetiology of inflammation in ileal pouches following restorative proctocolectomy. It is proposed that many of these processes may be involved in the pathogenesis of ulcerative colitis, and therefore pouchitis may be used to study pathogenesis and treatment of inflammatory bowel disease in general and, in particular, ulcerative colitis. PMID- 8196558 TI - Cell loss and tumor growth revisited. AB - Cell loss is a biological phenomenon that occurs in normal and neoplastic tissue and is an important kinetic factor which contributes to the dynamic state of tumor growth. This relevant phenomenon which was introduced by tumor biologists in the early 1970s while studying tumor growth kinetics has been largely neglected in cancer therapy, although with adequate research it may hold potential for future strategies in cancer treatment. Cell loss occurs through various mechanisms which include exfoliation, metastasis, differentiation and cell death. Methods used for measuring cell loss will be examined and the importance of cell loss in tumor growth will be discussed. PMID- 8196559 TI - Mucosal origin of AIDS. AB - The natural history of AIDS implies sexual and breast-milk transmission of HIV across the mucosal lining of digestive and reproductive organs. Intraepithelial mucosal lymphocytes specialized in handling foods, air-borne, and microbial pathogens crossing the mucosal barrier represent up to 90% of immunocompetent cells in a human body. Enteropathy and respiratory infections, the main symptoms and cause of death in AIDS, are attributed to the failure of mucosal immunity. PMID- 8196560 TI - An unstable nuclear matrix may contribute to genetic instability. AB - Cancer cells proliferate and metastasize against the body's defense mechanisms due to their ability to change in response to challenges, both from the body's internal defenses as well as those from external sources, such as radiation and chemotherapy. This ability of tumor cell populations to change and grow in response to these stresses as well as to hold populations of cells with diverse abilities has been termed 'tumor cell heterogeneity'. Tumor cell heterogeneity is thought to arise in cancer cell populations as a result of genetic instability, an undefined process by which the genetic material of the cell is rendered more labile and more likely to undergo changes in structure, conformation, and function. DNA is structurally and functionally organized by the nuclear matrix, the dynamic RNA-protein skeleton of the nucleus. We provide here a proposal that provides a framework for understanding genetic instability in terms of an unstable nuclear matrix. PMID- 8196561 TI - Why do we eat? AB - The urge to eat is the main apparent issue underlying obesity. Although vast information regarding the physiology and psychology of eating behavior has been accumulated, a comprehensive concept is still missing. The model presented suggests that feeding behavior is ultimately controlled by the rate of work performed in the muscle or in an as yet unidentified compartment. It suggests a novel approach of a dynamic set-point weight and explains why diets usually fail to resolve the disorder while physical activity is beneficial in losing excess weight. Obesity is presented as a syndrome of high efficiency of energy conversion resulting in a variety of symptoms of which over-weight is only the more apparent. Other symptoms manifested in the predisposition to a variety of illnesses constitute the main health problem and can prevail in the obese subject even without the excess weight. Therefore, resolution of the disorder requires developing approaches which directly affect the efficiency of energy conversion. PMID- 8196562 TI - Apical left ventricular aneurysms and cardiac parasympathetic innervation in Chagas' heart disease. AB - Left ventricular apical aneurysms are present in Chagasic patients who have normal cardiac parasympathetic innervation. Cardiac parasympathetic abnormalities are found, in later stages of the disease, when diffuse myocardial damage and ventricular dilatation are already present. The apical region of the left ventricle is also affected in several acute and chronic non-Chagasic cardiac diseases. Therefore, thinning of the left ventricular apex, with aneurysm formation, may be a non-specific myocardial sequelae, secondary to myocardial damage. PMID- 8196563 TI - Biological uniqueness and the definition of normality. Part 1--The concept of 'intrinsic' homeostasis. AB - The patterns of biochemical and physiological variables values are subject specific and quite stable over time. Thus, within the limits imposed by physiological requirements, the composition of the 'milieu interieur' varies between individuals. It follows that having all values of blood constituents within the norm (defined statistically from populations of healthy subjects) might not be sufficient to identify biological normality, and a revised definition of biological normality should take into account inter-individual differences. Our concept of 'intrinsic' homeostasis means that the differences between subjects' concentrations of blood constituents express subject-specific constraints in the organization of their physiology, and that these differences might play a greater role than usually recognized. We list the consequences for medical research of the existence of biological uniqueness and propose to give more importance to the study of biological 'fingerprints' and 'intrinsic' homeostasis in physiology and clinical medicine. PMID- 8196564 TI - Biological uniqueness and the definition of normality. Part 2--The endocrine 'fingerprint' of healthy adults. AB - In an accompanying paper, we discussed the relevance of biological uniqueness for research in physiology and medicine. We proposed the concepts of subject-specific homeostasis, or 'intrinsic' homeostasis. Here, we illustrate this concept with the example of the endocrine 'fingerprint'. 9 hormones were measured in the blood of 8 normal subjects during 2 consecutive mornings, under a standardised resting condition. The concentrations of the hormones were subject-specific. They varied up to 6-fold between subjects, but were stable from one day to the next for each individual. TSH and FSH showed the wider inter-individual range of values, together with a very high level of day-to-day stability (r = 0.99 in both cases). In contrast, the inter-individual range of cortisol concentration was the smallest (1.5-fold) and the day-to-day stability of cortisol concentrations within each subject was low. A total of 21 non-hormonal variables were also measured. They varied less than hormones between subjects, but, with the exception of the electrolytes, most showed stability over the 2 days of sampling. We conclude that the organisation of hormonal and non-hormonal homeostasis varies between subjects to a greater extent than generally acknowledged and suggest that these differences express subject-specific constraints in the organization of homeostasis. PMID- 8196565 TI - [Oxygen radicals and atherosclerosis]. PMID- 8196566 TI - [Risk factors and safety of intrauterine devices]. PMID- 8196567 TI - [Serious specialist publications]. PMID- 8196568 TI - [Lice infestation of humans]. PMID- 8196569 TI - Venlafaxine--a new antidepressant. PMID- 8196570 TI - LAAM--a long-acting methadone for treatment of heroin addiction. PMID- 8196571 TI - [Empirical antimicrobial therapy in neutropenic patients. Results of a multicenter study by the Infections in Hematology Study Group of the Paul Ehrlich Society]. AB - BACKGROUND: Severe infections are the predominant cause of treatment failure in patients with high grade malignant hematological disorders undergoing intensive chemotherapy. PATIENTS AND METHODS: In a multicenter trial of the Paul Ehrlich Society (PEG) study group, febrile neutropenic patients with acute leukemias or other high grade hematological malignancies were randomized for a three phase sequential antimicrobial intervention comparing different widely applied regimes for empirical therapy. Patients with clinically documented infections were treated according to a modification depending on the respective source of infection, whereas in patients with microbiologically documented infections, treatment could be adapted to the sesceptibility patterns of detected pathogens. Criteria for evaluation as well as time points for response assessment and treatment escalation were strictly prescribed by the study protocol. RESULTS: Of 1573 evaluable patients, 50.9% had fever of unknown origin (FUO) throughout the study period, 17.1% had lung infiltrates, 14.1% primary bacteremia or fungemia (B/F), 12.6% other clinically documented (CDI) and 5.3% other clinically as well as microbiologically documented infections (CMDI). Cumulative response rate (CR) in patients with FUO was 91.3%, a significant difference between various regimens could not be detected in either of the three treatment phases. Patients with lung infiltrates had a significantly worse treatment outcome as compared to patients with other documented infections or with FUO (61.3% vs 82.9% vs 91.3%). Gram positive pathogens dominated in case of microbiologically documented infections (MDI), whereas the proportion of fungal infections increased dramatically in MDI with pathogens detected only after more than six days under study. Of numerous prognostic factors analyzed, only the trend in white blood cell counts had a significant impact on treatment outcome. CONCLUSION: Infection-related mortality in neutropenic patients with high grade hematological malignancies can be markedly reduced by a systematically escalating interventional antimicrobial therapy. Early systemic antifungal treatment, especially in patients with lung infiltrates, might further improve treatment results. PMID- 8196573 TI - [Primary and secondary prevention of Pneumocystis carinii pneumonia with pentamidine aerosol. Effectiveness, side effects and incidence of extrapulmonary Pneumocystis carinii manifestations]. AB - BACKGROUND: We report on a retrospective study in 544 HIV-positive patients, (42 women, 502 men, mean age 35 years) showing CD4 lymphocyte counts below 200 c/mcl or after their cure of Pneumocystis carinii pneumonia, who received 300 mg pentamidine aerosol as prophylaxis against Pneumocystis carinii pneumonia every four week. PATIENTS AND METHODS: 277 patients were asymptomatic, 120 in the AIDS related complex stage (ARC) and 147 in the full stage of AIDS. The mean follow-up was 14.4 months. RESULTS: A total of 25 cases of Pneumocystis carinii pneumonia was observed (3.83/year): in the primary prophylaxis group 18 (3.25%/year), in the secondary prophylaxis group seven (6.8%/year). By introducing the loading dose (one inhalation per day for five consecutive days for patients with CD4 cell counts below 150 c/mcl) we reduced the percentage of early manifestations within the first three months from 61% to 14%. No extrapulmonary Pneumocystis carinii manifestation was observed. CONCLUSION: This study supports the efficacy of pentamidine aerosol prophylaxis of primary and secondary Pneumocystis carinii pneumonia. PMID- 8196572 TI - [Mexiletine in treatment of painful diabetic neuropathy]. AB - The objective of this double-blind placebo controlled multicenter study was to prove the efficacy of mexiletine in painful diabetic neuropathy. Treatment was provided for in three dosages. For pain measurements a visual analogue scale (VAS) and McGill's verbal rating scale were chosen. 95 patients were included. A global assessment of the VAS showed no differences in treatment. The total evaluation (PRIT = Pain Rating Index Total) of the McGill scale just failed the level of significance. More specific exploratory evaluation of subclasses of the McGill scale, representing different qualities of pain, gave remarkable differences between mexiletine and placebo. According to types of complaints an evaluation showed substantial advantages of the mexiletine treatment with both the VAS and the McGill scale. There is strong evidence that particularly patients with stabbing or burning pain, heat sensations or formication will benefit most by mexiletine therapy. Concerning the dosage, a medium regimen of 450 mg per day seems to be appropriate in this indication. With an increase in dosage the efficacy does not rise proportionally. Mexiletine proved a very safe therapy with negligible side effects at the medium dose range, even less than placebo. There were no cardiovascular side effects. Further investigations should pay more attention to the variety of the complaints and include the quality of life. PMID- 8196574 TI - [Refractory vomiting in a 61-year-old patient]. PMID- 8196575 TI - ['94 pneumology update. Progress and perspectives in pneumology. Paradigm of change (I)]. PMID- 8196576 TI - [Chronic fatigue syndrome]. PMID- 8196577 TI - [Contrast echocardiography detection and hemodynamic effects of intrapulmonary shunt in liver cirrhosis]. PMID- 8196579 TI - [Microhematuria and hypercalciuria in children]. PMID- 8196578 TI - [The pathogenetic basis of nephrolithiasis]. PMID- 8196580 TI - [Urolithiasis in childhood: clinical and imaging diagnosis]. PMID- 8196581 TI - [Epidemiology of urolithiasis in infancy]. PMID- 8196582 TI - [Urolithiasis in infancy: medical therapy of calculosis and prevention of recurrences]. PMID- 8196583 TI - [Alternative techniques to 'open surgery' in the treatment of renal- ureteral calculosis in adults]. PMID- 8196584 TI - [Extracorporeal shock wave lithotripsy: experience in childhood]. PMID- 8196585 TI - [Urolithiasis in infancy : present indications for surgical treatment]. PMID- 8196586 TI - Risky driving behaviors among teenagers--Gwinnett County, Georgia, 1993. AB - In the United States in 1991, approximately 6000 persons aged 16-20 years died from motor-vehicle crashes (MVCs)--twice as many as from any other cause of death among persons in this age group. During 1991, approximately 3000 crashes in Gwinnett County, Georgia (1990 population: 352,910) (26% of all crashes in Gwinnett County), involved at least one teenage driver (Gwinnett County Department of Transportation, unpublished data, 1992). Risky driving behaviors are among the risk factors for teenage MVC death and injury. To better characterize these risk factors, the Georgia Department of Human Resources, the Gwinnett County Board of Health, the community-based Gwinnett County Teen Traffic Tragedies Task Force, and CDC conducted a case-control study of MVCs among teenage drivers in Gwinnett County during 1993. This report summarizes the results of that study. PMID- 8196587 TI - Multidrug-resistant tuberculosis in a hospital--Jersey City, New Jersey, 1990 1992. AB - Since 1986 (the first full year following implementation of the revised tuberculosis [TB] surveillance case definition), the reported rate of TB per 100,000 persons in New Jersey increased from 9.5 cases to 12.6 cases in 1992. Of the 984 cases reported to CDC from New Jersey in 1992, 108 (11.0%) were reported from Jersey City (1990 population: 230,300)--the city ranked second in number of TB cases reported and fourth in rate of TB (46.9 per 100,000) in the state. In addition, in 1992, the rate of multidrug-resistant TB (MDR-TB) (i.e., Mycobacterium tuberculosis isolates resistant to at least isoniazid [INH] and rifampin [RIF]) among TB patients in New Jersey was 5%; the rate in Jersey City was 13%. To characterize the epidemiologic features of persons with drug resistant TB, the New Jersey Department of Health and the Infectious Diseases Division of the Jersey City Medical Center conducted a study among patients treated at that hospital during 1990-1992. This report presents the findings of the study and compares the hospital's rates of drug-resistant TB with previously reported rates, rates for other cities in New Jersey, and rates for the state. PMID- 8196588 TI - [A multi-institutional study for prevalence, diagnosis and treatment of deep fungal infection in gastrointestinal surgery]. AB - A multi-institutional study was conducted for prevalence, diagnosis and treatment of deep fungal infection in gastrointestinal surgery. Forty five cases including thirty six complete cases were entered basing on the diagnostic criteria and the mortality of complete cases was 17%. By the administration of miconazole (MCZ), clinical response rate was obtained in 87%, mycological radiation rate in 82% and valuable rate in 71%, with occurrence of side effects in 20%. Fungal endophthalmitis was found in 41% (12/29 cases). beta-glucan [the toxinometer method (T), the Seikagaku-Kogyo method (S)] and candida antigen [the C and-Tec method (C)] were monitored as sero-diagnostic methods, the positive rates for all cases, fungemia, and mycosis of which were 63, 83, 62% (T), 88, 100, 92% (S) and 52, 83, 50% (C), respectively. After mycological re-classification, the positive rates of the T method and endophthalmitis, and the mortality rates were 86, 60, 38% in fungemia, 63, 43, 23% in urinary tract infection, 64, 80, 7% in TPN infection, and 33, 17, 33% in drain infection, respectively. High association of endophthalmitis was found in TPN infection. The beta-glucan assay and a prospective ophthalmoscopic examination are useful for the early diagnosis of deep fungal infection and it is reasonable to treat patients in gastrointestinal surgery by MCZ when mycosis is confirmed or suspected. PMID- 8196589 TI - [Experimental study on the lymph flow of the esophagus by injecting cuttlefish particles into the esophageal wall]. AB - Cuttlefish particles which have an affinity with lymphatic pathways are useful for investigating the lymph flow from the esophagus, because they can be distinguished from anthracosis in the thoracic lymph nodes by means of melanine breeching method. Four days after injecting the cuttlefish particles into the esophageal walls of 103 mongrel dogs, intrathoracic and abdominal lymph nodes were dissected and examined histologically to know how much of the injected particles have migrated into lymph nodes. In case of spreading of injected particles limited to the muscle layer, the staining rate per number of cases in the right uppermost mediastinal nodes was higher when the particles were injected into the upper and middle esophagus (75%) than into the lower esophagus (0%, p < 0.002). The rate of staining in the lymph nodes along the left gastric artery was higher when the particles were injected into the anal side (100%) than into the oral side of the canter of middle esophagus (14%, p < 0.001). If these situations were duplicated in humans, lymph node dissection for thoracic esophageal cancer should reasonably be considered from the findings on tumor location and depth of invasion by the tumor. PMID- 8196590 TI - [Histologic and cell kinetic alteration of gastric mucosa under continuous duodenal regurgitation in experimental dog model]. AB - The experimental models for duodenal regurgitation were established using Schimilinisky-McCann's procedure in dogs. Histology, cell kinetics, and degree of DNA methylation in the gastric mucosa of those models were examined at 3, 6, and 12 month periods after the procedure and compared with those in normal mucosa. Histologically, minor changes of gastric mucosa such as superficial gastritis and erosion, were observed at the 3 month period, whereas hyperplasia and atrophy of the mucosa were observed at the 6 and 12 month periods, respectively. Cell kinetic analysis using bromodeoxyuridine (BrdU) and anti-BrdU antibodies revealed a significantly higher labeling index (L.I.) in the hyperplastic mucosa and also revealed a tendency of high L.I. in the atrophic mucosa at the 6 month period in comparison with that in normal mucosa. A high level of DNA methylation was identified in the mucosa that showed a high L.I. of BrdU at the 6 and 12 month periods. These results suggest that hyperplastic and subsequent atrophic changes of the gastric mucosa under continuous duodenal regurgitation are closely related with rapid cell proliferation and a high level of DNA methylation, and that the duodenal juice could play a crucial role in the carcinogenesis of the stomach. PMID- 8196591 TI - [Molecular oncological study on DNA ploidy, Ki-ras point mutation, and p21 expression in colorectal cancer]. AB - We studied DNA ploidy, point mutation of Ki-ras oncogene codon 12, and p21 expression using paraffin embedded materials from 42 cases of colorectal cancer. DNA ploidy was measured by the method of Hedley et al. flow cytometrically. Point mutation of Ki-ras oncogene was examined by the method of Bos et al. using a dot blot screening procedure, and p21 expression was examined immunohistochemically. Incidence of aneuploidy, Ki-ras point mutation, and p21 expression was 71.4%, 26.2%, 40.5%, respectively. There was a very weak correlation between p21 expression and pathologic findings, but there was no correlation between pathologic findings and DNA ploidy, as well as Ki-ras point mutation. Patients who showed aneuploidy tended to have more point mutation of Ki-ras oncogene. There was no correlation between p21 expression and Ki-ras point mutation, as well as DNA ploidy. Although there was no correlation between Ki-ras point mutation and survival, a significant correlation between survival and DNA ploidy, as well as p21 expression was recognized. Patients who had tumors with diploidy or p21 expression tended to have better prognosis. PMID- 8196592 TI - [An experimental study on the correlation between hepatic hemodynamics and ultrastructural and immunohistochemical changes in sinusoidal endothelial cells after major hepatectomy]. AB - The correlation between hepatic hemodynamics and changes of sinusoidal endothelial cells after major hepatectomy was studied using adult mongrel dogs. The sinusoidal endothelial cells were examined both ultrastructurally and immunohistochemically. Three types of hepatectomy, i.e., 30%, 70% and 84% resection, were applied to these animals, 16 each. The results obtained were as follows: 1) Portal vein pressure and the vascular resistance after operation were significantly higher in 70% hepatectomized dogs than those in 30% hepatectomized dogs. Twenty-four hours later, however, the difference was not significant. 2) Portal vein pressure and the vascular resistance after operation were much higher in 84% hepatectomized dogs than those in 30% and 70% hepatectomized dogs. Only 2 of 84% hepatectomized dogs survived more than 8 hours, and the two dogs also died of circulatory insufficiency 24 hours postoperatively. 3) Electron microscopic observation revealed that the sinusoidal endothelial fenestrae in 70% hepatectomized dogs were contracted 3 hours after operation but dilated 24 hours postoperatively. These changes in 70% hepatectomized dogs correlated well with hepatic hemodynamics. 4) Immunohistochemical observation using thrombomodulin staining method indicated that the sinusoidal endothelial cells in 84% hepatectomized dogs were seriously damaged 3 hours after operation. PMID- 8196593 TI - [Prognostic significance of DNA ploidy pattern on bile duct cancer]. AB - Of 33 patients surgically treated for bile duct cancer, nuclear DNA content of cancer cells was assessed by flow cytometry in order to determine whether DNA ploidy pattern was a prognostic indicator. Thirteen patients (40%) had diploid tumors and 20 patients (60%) had aneuploid tumors including 12 patients with DNA heterogeneity. No significant correlation was found between DNA ploidy pattern and clinicopathological features. Survival of patients with diploid tumor was significantly longer than those with aneuploid tumor (p < 0.01). In aneuploid cases, the prognosis of patients with DNA heterogeneity was similar to those without DNA heterogeneity. In the patients who underwent a curative resection, 5 year survival rate of diploid cases was 100%, as opposed that no patients with aneuploid tumor survived longer than 4 years. These results suggest that DNA ploidy pattern is a important prognostic determinant for bile duct cancer. PMID- 8196594 TI - [Early diagnosis of acute rejection in single lung transplantation from the standpoint of pulmonary hemodynamics]. AB - The aim of this study is to clarify the early phase of acute rejection of the single lung transplantation by the pulmonary hemodynamics. Twenty dogs were divided into 3 groups (Group I (6 dogs): Modified autotransplantation, Group II (6): Allotransplantation without immunosuppression, Group III (8): Allotransplantation with immunosuppression (CYA 10mg/kg, AZ 2mg/kg)). Cardiac output (CO) and pulmonary arterial (PA) flow of the transplanted lung were measured continuously using Doppler flow method. In Group I, PA flow was maintained at about 40% of CO for 2 weeks. However, in Group II, PA flow gradually decreased to 15% of CO on the 7th postoperative day (POC) and all animals died of rejection within 2 weeks after surgery. In Group III, PA flow decreased to 20% of CO on the 1st POD but, then increased gradually to 38% on the 14th POD. When rejection was induced by discontinuation of CYA and AZ, PA flow decreased to below 13% of CO within 3.7 days (mean) and perivascular cuffing was found in open biopsy, although findings on chest X-ray films remained unchanged. PA flow returned to 40% within 4.3 days (mean) by injecting methylprednisolone for 3 days. In conclusion, the measurement of pulmonary hemodynamics might be useful in the early diagnosis of acute rejection after single lung transplantation. PMID- 8196595 TI - [A case of Budd-Chiari syndrome treated by radical operation under hepatic perfusion and extracorporeal circulation]. AB - A 41-year-old male patient of Budd-Chiari syndrome associated with membranous obstructions of the retrohepatic inferior vena cava and the left hepatic vein was reported. A radical operation was carried out. The retrohepatic inferior vena cava was reconstructed by a ringed EPTFE patch graft after endovenectomy with the aid of extracorporeal circulation for caval and portal bypasses utilizing cold hepatic perfusion. The patient has been doing well 18 months after the operation. PMID- 8196596 TI - [Experimental study on the changes of Ca2+ during porcine liver transplantation: preliminary report]. PMID- 8196597 TI - [Stress-free surgery might be possible by continuous hemodiafiltration? Preliminary report]. PMID- 8196598 TI - [A model of peritoneal dissemination of gastric scirrhous carcinoma cells in nude mice: preliminary report]. PMID- 8196599 TI - [The effects of cardioplegic solution with Ni2+ upon ischemia-reperfusion in the isolated rat hearts: preliminary report]. PMID- 8196600 TI - Activation and inhibition of erythropoietin receptor function: role of receptor dimerization. AB - Members of the cytokine receptor superfamily have structurally similar extracellular ligand-binding domains yet diverse cytoplasmic regions lacking any obvious catalytic domains. Many of these receptors form ligand-induced oligomers which are likely to participate in transmembrane signaling. A constitutively active (factor-independent) mutant of the erythropoietin receptor (EPO-R), R129C in the exoplasmic domain, forms disulfide-linked homodimers, suggesting that the wild-type EPO-R is activated by ligand-induced homodimerization. Here, we have taken two approaches to probe the role EPO-R dimerization plays in signal transduction. First, on the basis of the crystal structure of the ligand-bound, homodimeric growth hormone receptor (GH-R) and sequence alignment between the GH R and EPO-R, we identified residues of the EPO-R which may be involved in intersubunit contacts in an EPO-R homodimer. Residue 129 of the EPO-R corresponds to a residue localized to the GH-R dimer interface region. Alanine or cysteine substitutions were introduced at four other residues of the EPO-R predicted to be in the dimer interface region. Substitution of residue E-132 or E-133 with cysteine renders the EPO-R constitutively active. Like the arginine-to-cysteine mutation at position 129 in the exoplasmic domain (R129C), E132C and E133C form disulfide-linked homodimers, suggesting that constitutive activity is due to covalent dimerization. In the second approach, we have coexpressed the wild-type EPO-R with inactive mutants of the receptor missing all or part of the cytosolic domain. These truncated receptors have a dominant inhibitory effect on the proliferative action of the wild-type receptor. Taken together, these results strengthen the hypothesis that an initial step in EPO- and EPO-R-mediated signal transduction is ligand-induced receptor dimerization. PMID- 8196601 TI - Dorsal, a Drosophila Rel-like protein, is phosphorylated upon activation of the transmembrane protein Toll. AB - The nuclear import of dorsal, a Drosophila Rel homolog, is directed by a spatially restricted extracellular ligand in blastoderm embryos. We have demonstrated both that dorsal is an embryonic phosphoprotein and that its phosphorylation state is regulated by an intracellular signaling pathway initiated by the transmembrane receptor Toll. Immunoblot analysis of cytoplasm from precisely staged embryos revealed that the phosphorylation state of dorsal is altered during the time period that Toll is activated. Moreover, mutations that constitutively activate Toll stimulated dorsal phosphorylation, while mutations that block Toll activation reduced the level of dorsal phosphorylation. We further demonstrated that signal-dependent dorsal phosphorylation is modulated by three intracellular proteins, pelle, tube, and cactus. Using double-mutant embryos, we then explored the nature of the kinase activity responsible for dorsal phosphorylation. We found that free dorsal is a substrate for a signal independent kinase activity. In addition, our results imply that dorsal is a substrate for a Toll-dependent kinase. These results are consistent with the hypothesis that phosphorylation of Rel-related proteins may be required for the proper nuclear localization and transcriptional activity of these proteins. PMID- 8196602 TI - Yeast nucleotide excision repair proteins Rad2 and Rad4 interact with RNA polymerase II basal transcription factor b (TFIIH). AB - The Rad2, Rad3, Rad4, and Ss12 proteins are required for nucleotide excision repair in yeast cells and are homologs of four human proteins which are involved in a group of hereditary repair-defective diseases. We have previously shown that Rad3 protein is one of the five subunits of purified RNA polymerase II basal transcription initiation factor b (TFIIH) and that Ss12 protein physically associates with factor b (W.J. Feaver, J.Q. Svejstrup, L. Bardwell, A.J. Bardwell, S. Buratowski, K.D. Gulyas, T.F. Donahue, E.C. Friedberg, and R.D. Kornberg, Cell 75:1379-1387, 1993). Here we show that the Rad2 and Rad4 proteins interact with purified factor b in vitro. Rad2 (a single-stranded DNA endonuclease) specifically interacts with the Tfb1 subunit of factor b, and we have mapped a limited region of the Rad2 polypeptide which is sufficient for this interaction. Rad2 also interacts directly with Ss12 protein (a putative DNA helicase). The binding of Rad2 and Rad4 proteins to factor b may define intermediates in the assembly of the nucleotide excision repair repairosome. Furthermore, the loading of factor b (or such intermediates) onto promoters during transcription initiation provides a mechanism for the preferential targeting of repair proteins to actively transcribing genes. PMID- 8196603 TI - Role of IRS-1-GRB-2 complexes in insulin signaling. AB - GRB-2 is a small SH2- and SH3 domain-containing adapter protein that associates with the mammalian SOS homolog to regulate p21ras during growth factor signaling. During insulin stimulation, GRB-2 binds to the phosphorylated Y895VNI motif of IRS-1. Substitution of Tyr-895 with phenylalanine (IRS-1F-895) prevented the IRS 1-GRB-2 association in vivo and in vitro. The myeloid progenitor cell line, 32-D, is insensitive to insulin because it contains few insulin receptors and no IRS-1. Coexpression of IRS-1 or IRS-1F-895 with the insulin receptor was required for insulin-stimulated mitogenesis in 32-D cells, while expression of the insulin receptor alone was sufficient to mediate insulin-stimulated tyrosine phosphorylation of Shc and activation of p21ras and mitogen-activated protein (MAP) kinase. The Shc-GRB-2 complex formed during insulin stimulation is a possible mediator of p21ras and MAP kinase activation in IRS-1-deficient 32-D cells. Interestingly, IRS-1, but not IRS-1F-895, enhanced the stimulation of MAP kinase by insulin in 32-D cells expressing insulin receptors. Thus, IRS-1 contributes to the stimulation of MAP kinase by insulin, probably through formation of the IRS-1-GRB-2 complex at Tyr-895. Our results suggest that the Shc GRB-2 complex and the activation of p21ras-dependent signaling pathways, including MAP kinase, are insufficient for insulin-stimulated mitogenesis and that the essential function(s) of IRS-1 in proliferative signaling is largely unrelated to IRS-1-GRB-2 complex formation. PMID- 8196604 TI - TFIIIR is an isoleucine tRNA. AB - Promoter-specific transcription by silkworm RNA polymerase III is dependent on several transcription factors (TFs) in addition to the polymerase itself. The activities present in silk gland nuclear extracts that are necessary to reconstitute transcription from class III genes in vitro have been resolved into several partially purified components. These include TFIIIR, which is unusual because it is composed of RNA. Here, we identify the RNA that provides TFIIIR activity as silkworm tRNA(IleIAU). This conclusion is based on copurification of tRNA(IleIAU) with TFIIIR activity, TFIIIR activity in synthetic tRNA(Ile), and hybrid selection of TFIIIR activity by antisense tRNA(IleIAU). We have tested the ability of a variety of other tRNAs to stimulate transcription and find that TFIIIR activity is highly specific to silkworm tRNA(IleIAU). PMID- 8196605 TI - tRNA(IleIAU) (TFIIIR) plays an indirect role in silkworm class III transcription in vitro and inhibits low-frequency DNA cleavage. AB - tRNA(IleIAU) provides an activity, originally called TFIIIR, necessary to reconstitute transcription by silkworm RNA polymerase III in vitro from partially purified components. Here we report studies on the role of tRNA(IleIAU) in in vitro transcription. We show that tRNA(IleIAU) does not act positively but, rather, is required to prevent the action of a transcriptional inhibitor. We also show that the presence of tRNA(IleIAU) in transcription reaction mixtures prevents low-frequency DNA cleavage by the TFIIIB fraction. Studies on the mechanism of transcriptional inhibition suggest that this DNA cleavage could cause transcriptional inhibition through trans-inactivation of transcription machinery. The ability to block DNA cleavage, like the ability to facilitate transcription, is highly specific to silkworm tRNA(IleIAU). PMID- 8196606 TI - Effect of a null mutation of the insulin-like growth factor I receptor gene on growth and transformation of mouse embryo fibroblasts. AB - Fibroblast cell lines, designated R- and W cells, were generated, respectively, from mouse embryos homozygous for a targeted disruption of the Igf1r gene, encoding the type 1 insulin-like growth factor receptor, and from their wild-type littermates. W cells grow normally in serum-free medium supplemented with various combinations of purified growth factors, while pre- and postcrisis R- cells cannot grow, as they are arrested before entering the S phase. R- cells are able to grow in 10% serum, albeit more slowly than W cells, and with all phases of the cell cycle being elongated. An activated Ha-ras expressed from a stably transfected plasmid is unable to overcome the inability of R- cells to grow in serum-free medium supplemented with purified clones. Nevertheless, even in the presence of serum, R- cells stably transfected with Ha-ras, alone or in combination with simian virus 40 large T antigen, fail to form colonies in soft agar. Reintroduction into R- cells (or their derivatives) of a plasmid expressing the human insulin-like growth factor I receptor RNA and protein restores their ability to grow with purified growth factors or in soft agar. The signaling pathways participating in cell growth and transformation are discussed on the basis of these results. PMID- 8196607 TI - A carbon source-responsive promoter element necessary for activation of the isocitrate lyase gene ICL1 is common to genes of the gluconeogenic pathway in the yeast Saccharomyces cerevisiae. AB - The expression of yeast genes encoding gluconeogenic enzymes depends strictly on the carbon source available in the growth medium. We have characterized the control region of the isocitrate lyase gene ICL1, which is derepressed more than 200-fold after transfer of cells from fermentative to nonfermentative growth conditions. Deletion analysis of the ICL1 promoter led to the identification of an upstream activating sequence element, UASICL1 (5' CATTCATCCG 3'), necessary and sufficient for conferring carbon source-dependent regulation on a heterologous reporter gene. Similar sequence motifs were also found in the upstream regions of coregulated genes involved in gluconeogenesis. This carbon source-responsive element (CSRE) interacts with a protein factor, designated Ang1 (activator of nonfermentative growth), detectable only in extracts derived from derepressed cells. Gene activation mediated by the CSRE requires the positively acting derepression genes CAT1 (= SNF1 and CCR1) and CAT3 (= SNF4). In the respective mutants, Ang1-CSRE interaction was no longer observed under repressing or derepressing conditions. Since binding of Ang1 factor to the CSRE could be competed for by an upstream sequence derived from the fructose-1,6-bisphosphatase gene FBP1, we propose that the CSRE functions as a UAS element common to genes of the gluconeogenic pathway. PMID- 8196608 TI - Commitment of yeast pre-mRNA to the splicing pathway requires a novel U1 small nuclear ribonucleoprotein polypeptide, Prp39p. AB - The binding of a U1 small nuclear ribonucleoprotein (snRNP) particle to the 5' splice site region of a pre-mRNA is a primary step of intron recognition. In this report, we identify a novel 75-kDa polypeptide of Saccharomyces cerevisiae, Prp39p, necessary for the stable interaction of mRNA precursors with the snRNP components of the pre-mRNA splicing machinery. In vivo, temperature inactivation or metabolic depletion of Prp39p blocks pre-mRNA splicing and causes growth arrest. Analyses of cell extracts reveal a specific and dramatic increase in the electrophoretic mobility of the U1 snRNP particle upon Prp39p depletion and demonstrate that extracts deficient in Prp39p activity are unable to form either the CC1 or CC2 commitment complex band characteristic of productive U1 snRNP/pre mRNA association. Immunological studies establish that Prp39p is uniquely associated with the U1 snRNP and is recruited with the U1 snRNP into splicing complexes. On the basis of these and related observations, we propose that Prp39p functions, at least in part, prior to stable branch point recognition by the U1 snRNP particle to facilitate or stabilize the U1 snRNP/5' splice site interaction. PMID- 8196609 TI - TPD1 of Saccharomyces cerevisiae encodes a protein phosphatase 2C-like activity implicated in tRNA splicing and cell separation. AB - The Saccharomyces cerevisiae TPD1 gene has been implicated in tRNA splicing because a tpd1-1 mutant strain accumulates unspliced precursor tRNAs at high temperatures (W. H. van Zyl, N. Wills, and J. R. Broach, Genetics 123:55-68, 1989). The wild-type TPD1 gene was cloned by complementation of the tpd1-1 mutation and shown to encode a protein with substantial homology to protein phosphatase 2C (PP2C) of higher eukaryotes. Expression of Tpd1p in Escherichia coli results in PP2C-like activity. Strains deleted for the TPD1 gene exhibit multiple phenotypes: temperature-sensitive growth, accumulation of unspliced precursor tRNAs, sporulation defects, and failure of cell separation during mitotic growth. On the basis of the presence of these observable phenotypes and the fact that Tpd1p accounts for a small percentage of the observed PP2C activity, we argue that Tpd1p is a unique member of the PP2C family. PMID- 8196610 TI - Mitochondrial topoisomerase II activity is essential for kinetoplast DNA minicircle segregation. AB - Etoposide, a nonintercalating antitumor drug, is a potent inhibitor of topoisomerase II activity. When Trypanosoma equiperdum is treated with etoposide, cleavable complexes are stabilized between topoisomerase II and kinetoplast DNA minicircles, a component of trypanosome mitochondrial DNA (T. A. Shapiro, V. A. Klein, and P. T. Englund, J. Biol. Chem. 264:4173-4178, 1989). Etoposide also promotes the time-dependent accumulation of small minicircle catenanes. These catenanes are radiolabeled in vivo with [3H]thymidine. Dimers are most abundant, but novel structures containing up to five noncovalently closed minicircles are detectable. Analysis by two-dimensional gel electrophoresis and electron microscopy indicates that dimers joined by up to six interlocks are late replication intermediates that accumulate when topoisomerase II activity is blocked. The requirement for topoisomerase II is particularly interesting because minicircles do not share the features postulated to make this enzyme essential in other systems: for minicircles, the replication fork is unidirectional, access to the DNA is not blocked by nucleosomes, and daughter circles are extensively nicked and (or) gapped. PMID- 8196611 TI - Evidence that v-Src-induced phospholipase D activity is mediated by a G protein. AB - v-Src-induced increases in diglyceride are derived from phosphatidylcholine via a type D phospholipase (PLD) and a phosphatidic acid phosphatase. v-Src-induced PLD activity, as measured by PLD-catalyzed transphosphatidylation of phosphatidylcholine to phosphatidylethanol, is inhibited by GDP beta S, which inhibits G-protein-mediated intracellular signals. Similarly, v-Src-induced increases in diglyceride are also blocked by GDP beta S. In contrast to the PLD activity induced by v-Src, PLD activity induced by the protein kinase C agonist, 12-O-tetradecanoylphorbol-13-acetate (TPA), was insensitive to GDP beta S. Consistent with the involvement of a G protein in the activation of PLD activity by v-Src, GTP gamma S, a nonhydrolyzable analog of GTP that potentiates G-protein mediated signals, strongly enhanced PLD activity in v-Src-transformed cells relative to that in parental BALB/c 3T3 cells. The effect of GTP gamma S on PLD activity in v-Src-transformed cells was observed only when cells were prelabeled with [3H]myristate, which is incorporated exclusively into phosphatidylcholine, the substrate for the v-Src-induced PLD. There was no difference in the effect of GTP gamma S-induced PLD activity on v-Src-transformed and BALB/c 3T3 cells when the cells were prelabeled with [3H]arachidonate, which is not incorporated into phospholipids that are substrates for the v-Src-induced PLD. Similarly, GDP beta S inhibited PLD activity in v-Src-transformed cells much more strongly than in BALB/c 3T3 cells when [3H]myristate was used to prelabel the cells. The GTP dependent activation of PLD by v-Src was dependent upon the presence of ATP but was unaffected by either cholera or pertussis toxin. These data suggest that v Src induces PLD activity through a phosphorylation event and is mediated by a cholera and pertussis toxin-insensitive G protein. PMID- 8196612 TI - A novel inhibitor of cyclin-Cdk activity detected in transforming growth factor beta-arrested epithelial cells. AB - Transforming growth factor beta (TGF-beta) is a potent inhibitor of epithelial cell growth. Cyclins E and A in association with Cdk2 have been shown to play a role in the G1-to-S phase transition in mammalian cells. We have studied the effects of TGF-beta-mediated growth arrest on G1/S cyclins E and A. Inhibition of cyclin A-associated kinase by TGF-beta is primarily due to a decrease in cyclin A mRNA and protein. By contrast, while TGF-beta inhibits accumulation of cyclin E mRNA, the reduction in cyclin E protein is minimal. Instead, we find that the activation of cyclin E-associated kinase that normally accompanies the G1-to-S phase transition is inhibited. A novel inhibitor of cyclin-Cdk complexes was detected in TGF-beta-treated cell lysates. Inhibition is mediated by a heat stable protein that targets both Cdk2 and Cdc2 kinases. In G0-arrested cells, a similar inhibitor of Cdk2 kinase was detected. These data suggest the existence of an inhibitor of cyclin-dependent kinases induced under different conditions to mediate antiproliferative responses. PMID- 8196613 TI - Adenovirus E3 protein causes constitutively internalized epidermal growth factor receptors to accumulate in a prelysosomal compartment, resulting in enhanced degradation. AB - We have previously identified and characterized an integral membrane protein coded for by the early transcription region 3 (E3) of human group C adenoviruses that down-regulates the epidermal growth factor receptor (EGFR). The goal of this study was to characterize the early receptor trafficking events leading to enhanced EGFR degradation in adenovirus-infected cells. Specifically, we wished to determine whether adenovirus increases the rate of EGFR internalization or alters the subcellular compartmentalization of internalized EGFRs. Once the optimal time for measuring early trafficking events was determined, surface EGFRs were labeled with a cleavable biotin reagent to measure internalization rates and with a receptor-specific monoclonal antibody (MAb) conjugated to colloidal gold for intracellular localization studies. We first showed that the rate of EGFR internalization in adenovirus-infected cells is indistinguishable from the constitutive internalization rate for unoccupied EGFRs. The possibility that the E3 protein can affect trafficking of EGFRs internalized at a low constitutive rate was further supported by studies showing that adenovirus-mediated down regulation occurs independently of EGFR oligomerization and intrinsic EGFR tyrosine kinase activity, which are required for efficient ligand-induced internalization. Other tyrosine kinases inhibited by genistein are also not required for adenovirus-induced down-regulation. When the intracellular localization of EGFRs during adenovirus-mediated down-regulation was examined by electron microscopy, there was a threefold increase in the number of EGFRs localized to multivesicular bodies. The multivesicular body has been proposed to be important for regulating intracellular membrane protein sorting, since trafficking patterns for receptors that recycle and receptors that are degraded diverge in this organelle. These data therefore suggest that adenovirus may enhance EGFR degradation by causing constitutively internalized EGFRs to accumulate in a prelysosomal compartment. This is the first example of a mechanism that efficiently down-regulates EGFR without significantly increasing the rate of internalization or that does not require EGFR tyrosine kinase activity. Since viral proteins often mimic or modify a host counterpart, this suggests that there are normal physiological conditions when receptor destruction without tyrosine signalling is beneficial. PMID- 8196614 TI - Two types of RAS mutants that dominantly interfere with activators of RAS. AB - In the fission yeast Schizosaccharomyces pombe, ras1 regulates both sexual development (conjugation and sporulation) and cellular morphology. Two types of dominant interfering mutants were isolated in a genetic screen for ras1 mutants that blocked sexual development. The first type of mutation, at Ser-22, analogous to the H-rasAsn-17 mutant (L. A. Feig and G. M. Cooper, Mol. Cell. Biol. 8:3235 3243, 1988), blocked only conjugation, whereas a second type of mutation, at Asp 62, interfered with conjugation, sporulation, and cellular morphology. Analogous mutations at position 64 of Saccharomyces cerevisiae RAS2 or position 57 of human H-ras also resulted in dominant interfering mutants that interfered specifically and more profoundly than mutants of the first type with RAS-associated pathways in both S. pombe or S. cerevisiae. Genetic evidence indicating that both types of interfering mutants function upstream of RAS is provided. Biochemical evidence showing that the mutants are altered in their interaction with the CDC25 class of exchange factors is presented. We show that both H-rasAsn-17 and H-rasTyr-57, compared with wild-type H-ras, are defective in their guanine nucleotide dependent release from human cdc25 and that this defect is more severe for the H rasTyr-57 mutant. Such a defect would allow the interfering mutants to remain bound to, thereby sequestering RAS exchange factors. The more severe interference phenotype of this novel interfering mutant suggests that it functions by titrating out other positive regulators of RAS besides those encoded by ste6 and CDC25. PMID- 8196615 TI - Equivalent mutations in the two repeats of yeast TATA-binding protein confer distinct TATA recognition specificities. AB - To investigate the process of TATA box recognition by the TATA box-binding protein (TBP), we have performed a detailed genetic and biochemical analysis of two Saccharomyces cerevisiae TBP mutants with altered DNA-binding specificity. The mutant proteins have amino acid substitutions (Leu-205 to Phe and Leu-114 to Phe) at equivalent positions within the two repeats of TBP that are involved in TATA element binding. In an in vivo assay that employs a nearly complete set of single point mutations of the consensus TATAAA sequence, one of the TBP mutants (TBP-L114F) recognizes the sequence TATAAG, while the other TBP mutant (TBP L205F) recognizes one substitution at the first position of the TATA element, CATAAA, and three substitutions at the 3' end of the TATA box. Specificity patterns determined from in vitro transcription experiments with purified recombinant wild-type TBP and TBP-L205F agree closely with those observed in vivo, indicating that altered TATA utilization in the mutant strains is a direct consequence of altered TATA recognition by the mutant TBPs. The distinct TATA recognition patterns exhibited by TBP-L114F and TBP-L205F strongly suggest that in vivo, TBP binds to the TATA element in a specific orientation. The orientation predicted from these studies is further supported by the identification of intragenic suppressors that correct the defect of TBP-L205F. This orientation is consistent with that observed in vitro by crystallographic analyses of TBP-TATA box complexes. Finally, the importance of altered DNA-binding specificity in transcriptional regulation at the S. cerevisiae his4-912 delta promoter was addressed for TBP-L205F. A mutational analysis of this promoter region demonstrates that the nonconsensus TATA element CATAAA is required for a transcriptional effect of TBP-L205F in vivo. This finding suggests that the interaction of TBP with nonconsensus TATA elements may play an important regulatory role in transcription initiation. PMID- 8196616 TI - Interactions of p59fyn and ZAP-70 with T-cell receptor activation motifs: defining the nature of a signalling motif. AB - The tyrosine-based activation motif is a 20- to 25-amino-acid sequence contained in the cytoplasmic domains of many hematopoietic receptors which is sufficient by itself to reconstitute signalling. This motif is characterized by two YXXL/I sequences separated by approximately 10 residues. The molecular basis of signalling by this motif is unknown. Here we demonstrate that the tyrosine-based activation motif is required and sufficient for association with the tyrosine kinases p59fyn and ZAP-70, suggesting that association with these kinases is a general feature of this motif. Focusing on the single activation motif present in epsilon, we analyzed which residues of the motif were critical for binding of p59fyn and ZAP-70. Surprisingly, we found that no single mutation of any residue of epsilon resulted in the loss of p59fyn association. In contrast, single mutations at five residues of the epsilon activating motif abrogated ZAP-70 binding. Both of the tyrosines and the leucine or isoleucine residues that follow them were critical. The spacing between the tyrosines was also important, as deletion of two residues disrupted binding of ZAP-70, although p59fyn binding was not disrupted. Most of the defined features of the tyrosine activation motif are therefore requirements for ZAP-70 binding. Interestingly, the interaction of ZAP 70 with the motif was dependent on the presence of both ZAP-70 SH2 domains and both of the tyrosine residues in the motif, suggesting that ZAP-70 interacts with two phosphotyrosine residues and that the binding of the two SH2 domains is cooperative. In addition, we demonstrate that the interaction between the tyrosine activation motif is direct and requires prior tyrosine phosphorylation of the motif. We propose that the activation of cells by the tyrosine activating motif occurs in four discrete steps: binding of p59fyn, phosphorylation of the motif, binding of ZAP-70, and activation of ZAP-70 kinase activity. PMID- 8196617 TI - Protein phosphatase 2C, encoded by ptc1+, is important in the heat shock response of Schizosaccharomyces pombe. AB - Protein phosphatase 2C (PP2C), an Mg(2+)-dependent enzyme that dephosphorylates serine and threonine residues, defines one of the three major families of structurally unrelated eukaryotic protein phosphatases. Members of the two other families of protein phosphatases are known to have important cellular roles, but very little is known about the biological functions of PP2C. In this report we describe a genetic investigation of a PP2C enzyme in the fission yeast Schizosaccharomyces pombe. We discovered ptc1+ (phosphatase two C) as a multicopy suppressor gene of swo1-26, a temperature-sensitive mutation of a gene encoding the heat shock protein hsp90. The ptc1+ gene product is a 40-kDa protein with approximately 24% identity to a rat PP2C protein. Purified Ptc1 has Mg(2+) dependent casein phosphatase activity, confirming that it is a PP2C enzyme. A ptc1 deletion mutant is viable and has approximately normal levels of PP2C activity, observations consistent with the fact that ptc1+ is a member of a multigene family. Although a ptc1 deletion mutant is viable, it has a greatly reduced ability to survive brief exposure to elevated temperature. Moreover, ptc1+ mRNA levels increase 5- to 10-fold during heat shock. These data, demonstrating that Ptc1 activity is important for survival of heat shock, provide one of the first genetic clues as to the biological functions of PP2C. PMID- 8196618 TI - PRL-1, a unique nuclear protein tyrosine phosphatase, affects cell growth. AB - PRL-1 is a particularly interesting immediate-early gene because it is induced in mitogen-stimulated cells and regenerating liver but is constitutively expressed in insulin-treated rat H35 hepatoma cells, which otherwise show normal regulation of immediate-early genes. PRL-1 is expressed throughout the course of hepatic regeneration, and its expression is elevated in a number of tumor cell lines. Sequence analysis reveals that PRL-1 encodes a 20-kDa protein with an eight-amino acid consensus protein tyrosine phosphatase (PTPase) active site. PRL-1 is able to dephosphorylate phosphotyrosine substrates, and mutation of the active-site cysteine residue abolishes this activity. As PRL-1 has no homology to other PTPases outside the active site, it is a new type of PTPase. PRL-1 is located primarily in the cell nucleus. Stably transfected cells which overexpress PRL-1 demonstrate altered cellular growth and morphology and a transformed phenotype. It appears that PRL-1 is important in normal cellular growth control and could contribute to the tumorigenicity of some cancer cells. PMID- 8196619 TI - A novel developmental regulatory motif required for stage-specific activation of the epsilon-globin gene and nuclear factor binding in embryonic erythroid cells. AB - Members of the human beta-globin gene family are expressed at discrete stages of development and therefore provide an important model system for examining mechanisms of temporal gene regulation. We have previously shown that expression of the embryonic beta-like globin gene (epsilon) is mediated by a complex array of positive and negative upstream control elements. Correct developmental stage- and tissue-specific gene expression is conferred by synergistic interactions between a positive regulatory element (termed epsilon-PRE II) which is active only in embryonic erythroid cells and at least two other regulatory domains upstream of the epsilon-globin gene promoter. A nuclear factor highly enriched in cultured embryonic erythroid cells and in mouse embryonic yolk sac binds to a novel, evolutionarily conserved sequence within epsilon-PRE II. We show here that binding of this factor to the conserved element within epsilon-PRE II is critical for transcriptional activity. Point mutations that interfere with protein binding to epsilon-PRE II abolish transcriptional activation of the constitutive epsilon globin promoter. Adult erythroid nuclei (from cultured cells or adult mouse liver) also contain a factor that binds to this region, but the complex formed migrates more rapidly during nondenaturing electrophoresis, suggesting either that distinct proteins bind to epsilon-PRE II or that a single protein is differentially modified in these cells in a way that modulates its activity. Several lines of evidence suggest that the binding factors in embryonic and adult erythroid cells are distinguished by posttranscriptional differences. PMID- 8196620 TI - Lipopolysaccharide induction of tissue factor gene expression in monocytic cells is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site. AB - Exposure of monocytic cells to bacterial lipopolysaccharide (LPS) activates the NF-kappa B/Rel family of proteins and leads to the rapid induction of inflammatory gene products, including tissue factor (TF). TF is the primary cellular initiator of the coagulation protease cascades. Here we report the characterization of a nuclear complex from human monocytic cells that bound to a kappa B-like site, 5'-CGGAGTTTCC-3', in the 5'-flanking region of the human TF gene. This nuclear complex was activated by LPS with kinetics that preceded induction of the TF gene. In vitro binding studies demonstrated that the TF site bound translated c-Rel and p65 homodimers but not p50/p65 heterodimers or p50 homodimers. Base-pair substitutions in the TF site indicated that the presence of a cytosine at position 1 precluded binding of NF-kappa B. In fact, under low ionic-strength conditions, the TF complex did not migrate with translated p50/p65 dimers but instead comigrated with c-Rel/p65 dimers. Antibodies against the NF kappa B and Rel proteins and UV cross-linking studies revealed the presence of c Rel and p65 and the absence of p50 in the TF complex and further showed that c Rel/p65 heterodimers selectively bound to the TF kappa B-like site. Functional studies indicated that the TF site conferred LPS inducibility on a heterologous promoter and was transactivated by c-Rel or p65. Taken together, our results demonstrated that binding of c-Rel/p65 heterodimers to a novel kappa B-like site mediated LPS induction of TF gene expression in monocytic cells. PMID- 8196621 TI - The eta isoform of protein kinase C is localized on rough endoplasmic reticulum. AB - The eta isoform of protein kinase C, isolated from a cDNA library of mouse skin, has unique tissue and cellular distributions. It is predominantly expressed in epithelia of the skin, digestive tract, and respiratory tract in close association with epithelial differentiation. We report here that this isoform is localized on the rough endoplasmic reticulum in transiently expressing COS1 cells and constitutively expressing keratinocytes. By the use of polyclonal antibodies raised against peptides of the diverse D1 and D2/D3 regions, we found that immunofluorescent signals were strongest in the cytoplasm around the nucleus and became weaker toward the peripheral cytoplasm. Under immunoelectron microscopic examination, electron-dense signals were located on the rough endoplasmic reticulum and on the outer nuclear membrane which is continuous with the endoplasmic reticulum membrane. However, no signals were detected in the nucleus, inner nuclear membrane, smooth endoplasmic reticulum, Golgi apparatus, mitochondria, or plasma membrane. Treatment of the cells in situ with detergents suggested association of the isoform of protein kinase C with intracellular structures. By immunoblotting, a distinct single band with an M(r) of 80,000 was detected in whole-cell lysate and in rough microsomal and crude nuclear fractions, all of which contain outer nuclear membrane and/or rough endoplasmic reticulum. We further demonstrated the absence of a nuclear localization signal in the pseudosubstrate sequence. The present observation is not consistent with the report of Greif et al. (H. Greif, J. Ben-Chaim, T. Shimon, E. Bechor, H. Eldar, and E. Livneh, Mol. Cell. Biol. 12:1304-1311, 1992). PMID- 8196622 TI - The yeast GAL11 protein is involved in regulation of the structure and the position effect of telomeres. AB - GAL11 is an auxiliary transcription factor that functions either positively or negatively, depending on the structure of the target promoters and the combination of DNA-bound activators. In this report, we demonstrate that a gal11 delta mutation caused a decrease in the length of the telomere C1-3A tract, a derepression of URA3 when it is placed next to telomere, and an increase in accessibility of the telomeric region to dam methylase, indicating that GAL11 is involved in the regulation of the structure and the position effect of telomeres. The defective position effect in a gal11 delta strain was suppressed by overproduction of SIR3, whereas overexpression of GAL11 failed to restore the telomere position effect in a sir3 delta strain. Hyperproduced GAL11 could partially suppress the defect in silencing at HMR in a sir1 delta mutant but not that in a sir3 delta mutant, suggesting that GAL11 can replace SIR1 function partly in the silencing of HMR. Overproduced SIR3 also could restore silencing at HMR in sir1 delta cells. In contrast, SIR1 in a multicopy plasmid relieved the telomere position effect, especially in a gal11 delta mutant. Since chromatin structure is thought to play a major role in the silencing at both the HM loci and telomeres, GAL11 is likely to participate in the regional regulation of transcription by the HM loci and telomeres, GAL11 is likely to participate in the regional regulation of transcription by modulating the chromatin structure. PMID- 8196623 TI - DNA recognition by splicing variants of the Wilms' tumor suppressor, WT1. AB - The Wilms' tumor suppressor, WT1, is a zinc finger transcriptional regulator which exists as multiple forms owing to alternative mRNA splicing. The most abundant splicing variants contain a nine-nucleotide insertion encoding lysine, threonine, and serine (KTS) in the H-C link region between the third and fourth WT1 zinc fingers which disrupts binding to a previously defined WT1-EGR1 binding site. We have identified WT1[+KTS] binding sites in the insulin-like growth factor II gene and show that WT1[+KTS] represses transcription from the insulin like growth factor II P3 promoter. The highest affinity WT1[+KTS] DNA binding sites included nucleotide contacts involving all four WT1 zinc fingers. We also found that different subsets of three WT1 zinc fingers could bind to distinct DNA recognition elements. A tumor-associated, WT1 finger 3 deletion mutant was shown to bind to juxtaposed nucleotide triplets for the remaining zinc fingers 1, 2, and 4. The characterization of novel WT1 DNA recognition elements adds a new level of complexity to the potential gene regulatory activity of WT1. The results also present the possibility that altered DNA recognition by the dominant WT1 zinc finger 3 deletion mutant may contribute to tumorigenesis. PMID- 8196624 TI - Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin. AB - Transforming growth factor beta (TGF-beta) and activin bind to receptor complexes that contain two distantly related transmembrane serine/threonine kinases known as receptor types I and II. The type II receptors determine ligand binding specificity, and each interacts with a distinct repertoire of type I receptors. Here we identify a new type I receptor for activin, ActR-IB, whose kinase domain is nearly identical to that of the recently cloned TGF-beta type I receptor, T beta R-I. ActR-IB has the structural and binding properties of a type I receptor: it binds activin only in the presence of an activin type II receptor and forms a heteromeric noncovalent complex with activin type II receptors. In Mv1Lu lung epithelial cells, ActR-IB and T beta R-I signal a common set of growth-inhibitory and transcriptional responses in association with their corresponding ligands and type II receptors. The transcriptional responses include elevated expression of fibronectin and plasminogen activator inhibitor 1. Although T beta R-I and ActR IB are nearly identical in their kinase domains (90% amino acid sequence identity), their corresponding type II receptor kinase domains are very different from each other (42% amino acid sequence identity). Therefore, signaling of a specific set of responses by TGF-beta and activin correlates with the presence of similar type I kinases in their complex. Indeed, other TGF-beta and activin type I receptors (TSR-I and ActR-I) whose kinase domains significantly diverge from those of T beta R-I and ActR-IB do not substitute as mediators of these growth inhibitory and extracellular matrix transcriptional responses. Hence, we conclude that the type I receptor subunits are primary specifiers of signals sent by TGF beta and activin receptor complexes. PMID- 8196625 TI - Vertebrate mRNAs with a 5'-terminal pyrimidine tract are candidates for translational repression in quiescent cells: characterization of the translational cis-regulatory element. AB - The translation of mammalian ribosomal protein (rp) mRNAs is selectively repressed in nongrowing cells. This response is mediated through a regulatory element residing in the 5' untranslated region of these mRNAs and includes a 5' terminal oligopyrimidine tract (5' TOP). To further characterize the translational cis-regulatory element, we monitored the translational behavior of various endogenous and heterologous mRNAs or hybrid transcripts derived from transfected chimeric genes. The translational efficiency of these mRNAs was assessed in cells that either were growing normally or were growth arrested under various physiological conditions. Our experiments have yielded the following results: (i) the translation of mammalian rp mRNAs is properly regulated in amphibian cells, and likewise, amphibian rp mRNA is regulated in mammalian cells, indicating that all of the elements required for translation control of rp mRNAs are conserved among vertebrate classes; (ii) selective translational control is not confined to rp mRNAs, as mRNAs encoding the naturally occurring ubiquitin-rp fusion protein and elongation factor 1 alpha, which contain a 5' TOP, also conform this mode of regulation; (iii) rat rpP2 mRNA contains only five pyrimidines in its 5' TOP, yet this mRNA is translationally controlled in the same fashion as other rp mRNAs with a 5' TOP of eight or more pyrimidines; (iv) full manifestation of this mode of regulation seems to require both the 5' TOP and sequences immediately downstream; and (v) an intact translational regulatory element from rpL32 mRNA fails to exert its regulatory properties even when preceded by a single A residue. PMID- 8196626 TI - Multiple mechanisms provide rapid and stringent glucose repression of GAL gene expression in Saccharomyces cerevisiae. AB - Expression of the GAL genes of Saccharomyces cerevisiae is induced during growth on galactose by a well-characterized regulatory mechanism that relieves Gal80p inhibition of the Gal4p transcriptional activator. Growth on glucose overrides induction by galactose. Glucose repression acts at three levels to reduce GAL1 expression: (i) it reduces the level of functional inducer in the cell; (ii) it lowers cellular levels of Gal4p by repressing GAL4 transcription; and (iii) it inhibits Gal4p function through a repression element in the GAL1 promoter. We quantified the amount of repression provided by each mechanism by assaying strains with none, one, two, or all three of the repression mechanisms intact. In a strain lacking all three repression mechanisms, there was almost no glucose repression of GAL1 expression, suggesting that these are the major, possibly the only, mechanisms of glucose repression acting upon the GAL genes. The mechanism of repression that acts to reduce Gal4p levels in the cell is established slowly (hours after glucose addition), probably because Gal4p is stable. By contrast, the repression acting through the upstream repression sequence element in the GAL1 promoter is established rapidly (within minutes of glucose addition). Thus, these three mechanisms of repression collaborate to repress GAL1 expression rapidly and stringently. The Mig1p repressor is responsible for most (possibly all) of these repression mechanisms. We show that for GAL1 expression, mig1 mutations are epistatic to snf1 mutations, indicating that Mig1p acts after the Snf1p protein kinase in the glucose repression pathway, which suggests that Snf1p is an inhibitor of Mig1p. PMID- 8196627 TI - Identification of potential target genes for Adr1p through characterization of essential nucleotides in UAS1. AB - Adr1p is a regulatory protein in the yeast Saccharomyces cerevisiae that binds to and activates transcription from two sites in a perfect 22-bp inverted repeat, UAS1, in the ADH2 promoter. Binding requires two C2H2 zinc fingers and a region amino terminal to the fingers. The importance for DNA binding of each position within UAS1 was deduced from two types of assays. Both methods led to an identical consensus sequence containing only four essential base pairs: GG(A/G)G. The preferred sequence, TTGG(A/G)GA, is found in both halves of the inverted repeat. The region of Adr1p amino terminal to the fingers is important for phosphate contacts in the central region of UAS1. However, no base-specific contacts in this portion of UAS1 are important for DNA binding or for ADR1 dependent transcription in vivo. When the central 6 bp were deleted, only a single monomer of Adr1p was able to bind in vitro and activation in vivo was severely reduced. On the basis of these results and previous knowledge about the DNA binding site requirements, including constraints on the spacing and orientation of sites that affect activation in vivo, a consensus binding site for Adr1p was derived. By using this consensus site, potential Adr1p binding sites were located in the promoters of genes known to show ADR1-dependent expression. In addition, this consensus allowed the identification of new potential target genes for Adr1p. PMID- 8196628 TI - An E-box element localized in the first intron mediates regulation of the prothymosin alpha gene by c-myc. AB - In RAT1A fibroblasts, expression of the prothymosin alpha gene is under the transcriptional control of the c-myc proto-oncogene. We have now cloned the rat gene encoding prothymosin alpha and show that the cloned gene is regulated by c myc in vivo. We find that regulation by c-myc is mediated by sequences downstream of the transcriptional start site, whereas the promoter is constitutive and not regulated by c-myc. We have identified an enhancer element within the first intron that is sufficient to mediate a response to Myc and Max in transient transfection assays and to activation of estrogen receptor-Myc chimeras in vivo. We find that this element contains a consensus Myc-binding site (CACGTG). Disruption of this site abolishes the response to Myc and Max in both transient and stable assays. Mutants of either Myc or Max that are deficient for heterodimerization fail to regulate the prothymosin alpha gene, suggesting that a heterodimer between Myc and Max activates the prothymosin alpha gene. Our data define the prothymosin alpha gene as a bona fide target gene for c-myc. PMID- 8196629 TI - Fine-resolution mapping of spontaneous and double-strand break-induced gene conversion tracts in Saccharomyces cerevisiae reveals reversible mitotic conversion polarity. AB - Spontaneous and double-strand break (DSB)-induced gene conversion was examined in alleles of the Saccharomyces cerevisiae ura3 gene containing nine phenotypically silent markers and an HO nuclease recognition site. Conversions of these alleles, carried on ARS1/CEN4 plasmids, involved interactions with heteroalleles on chromosome V and were stimulated by DSBs created at HO sites. Crossovers that integrate plasmids into chromosomes were not detected since the resultant dicentric chromosomes would be lethal. Converted alleles in shuttle plasmids were easily transferred to Escherichia coli and analyzed for marker conversion, facilitating the characterization of more than 400 independent products from five crosses. This analysis revealed several new features of gene conversions. The average length of DSB-induced conversion tracts was 200 to 300 bp, although about 20% were very short (less than 53 bp). About 20% of spontaneous tracts also were also less than 53 bp, but spontaneous tracts were on average about 40% longer than DSB-induced tracts. Most tracts were continuous, but 3% had discontinuous conversion patterns, indicating that extensive heteroduplex DNA is formed during at least this fraction of events. Mismatches in heteroduplex DNA were repaired in both directions, and repair tracts as short as 44 bp were observed. Surprisingly, most DSB-induced gene conversion tracts were unidirectional and exhibited a reversible polarity that depended on the locations of DSBs and frameshift mutations in recipient and donor alleles. PMID- 8196630 TI - scid cells efficiently integrate hairpin and linear DNA substrates. AB - The scid mouse mutation affects V(D)J rearrangement and double-strand break repair. scid V(D)J rearrangement is characterized by defective coding joint formation which prevents the development of mature B and T cells. Hairpin DNA has been implicated in the formation of V(D)J coding joints. We found scid cells to be proficient in hairpin processing in the context of DNA integration. In addition, we found that the scid defect did not impair integration of linear DNA via nonhomologous recombination. Therefore, hairpin processing and integration of DNA into the genome are distinct from hypersensitivity to ionizing radiation and the defect in V(D)J recombination. PMID- 8196631 TI - Analysis of the structural genes encoding M-factor in the fission yeast Schizosaccharomyces pombe: identification of a third gene, mfm3. AB - We previously identified two genes, mfm1 and mfm2, with the potential to encode the M-factor mating pheromone of the fission yeast Schizosaccharomyces pombe (J. Davey, EMBO J. 11:951-960, 1992), but further analysis revealed that a mutant strain lacking both genes still produced active M-factor. Here we describe the isolation and characterization of a third M-factor gene, mfm3. A mutant lacking all three genes fails to produce M-factor, indicating that all functional M factor genes now have been identified. The triple mutant exhibits an absolute mating defect in M cells, a defect that is not rescued by addition of exogenous M factor. A mutational analysis reveals that all three mfm genes contribute to the production of M-factor. Their transcription is limited to M cells and requires the mat1-Mc and ste11 gene products. Each gene is induced when the cells are starved of nitrogen and further induced by a pheromone signal. Additionally, the signal transduction machinery associated with the pheromone response is required for transcription of the mfm genes in both stimulated and unstimulated cells. PMID- 8196632 TI - BCL3 encodes a nuclear protein which can alter the subcellular location of NF kappa B proteins. AB - BCL3 is a candidate proto-oncogene involved in the recurring translocation t(14;19) found in some patients with chronic lymphocytic leukemia. BCL3 protein acts as an I kappa B in that it can specifically inhibit the DNA binding of NF kappa B factors. Here, we demonstrate that BCL3 is predominantly a nuclear protein and provide evidence that its N terminus is necessary to direct the protein into the nucleus. In contrast to I kappa B alpha (MAD3), BCL3 does not cause NF-kappa B p50 to be retained in the cytoplasm; instead, in cotransfection assays, it alters the subnuclear localization of p50. The two proteins colocalize, suggesting that they interact in vivo. Further immunofluorescence experiments showed that a mutant p50, lacking a nuclear localization signal and restricted to the cytoplasm, is brought into the nucleus in the presence of BCL3. Correspondingly, a wild-type p50 directs into the nucleus a truncated BCL3, which, when transfected alone, is found in the cytoplasm. We tested whether BCL3 could overcome the cytoplasmic retention of p50 by I kappa B alpha. Results from triple cotransfection experiments with BCL3, I kappa B alpha, and p50 implied that BCL3 can successfully compete with I kappa B alpha and bring p50 into the nucleus; thus, localization of NF-kappa B factors may be affected by differential expression of I kappa B proteins. These novel properties of BCL3 protein further establish BCL3 as a distinctive member of the I kappa B family. PMID- 8196633 TI - RNA polymerase II cofactor PC2 facilitates activation of transcription by GAL4-AH in vitro. AB - We have isolated from a crude Hela cell cofactor fraction (USA) a novel positive cofactor that cooperates with the general transcription machinery to effect efficient stimulation of transcription by GAL4-AH, a derivative of the Saccharomyces cerevisiae regulatory factor GAL4. PC2 was shown to be a 500-kDa protein complex and to be functionally and biochemically distinct from native TFIID and previously identified cofactors. In the presence of native TFIID and other general factors, PC2 was necessary and sufficient for activation by GAL4 AH. Cofactor function was specific for transcriptional activation domains of GAL4 AH. The repressor histone H1 further potentiated but was not required for activation of transcription by GAL4-AH. On the basis of the observation that PC2 exerts entirely positive effects on transcription, we propose a model in which PC2 increases the activity of the preinitiation complex in the presence of an activator, thereby establishing a specific pathway during activation of RNA polymerase II. PMID- 8196634 TI - A human Alu RNA-binding protein whose expression is associated with accumulation of small cytoplasmic Alu RNA. AB - Human Alu sequences are short interspersed DNA elements which have been greatly amplified by retrotransposition. Although initially derived from the 7SL RNA component of signal recognition particle (SRP), the Alu sequence has evolved into a dominant transposon while retaining a specific secondary structure found in 7SL RNA. We previously characterized a set of Alu sequences which are expressed as small cytoplasmic RNAs and isolated a protein that binds to these transcripts. Here we report that biochemical purification of this protein revealed it as the human homolog of the SRP 14 polypeptide which binds the Alu-homologous region of 7SL RNA. The human cDNA predicts an alanine-rich C-terminal tail translated from a trinucleotide repeat not found in the rodent homolog, which accounts for why the human protein-RNA complex migrates more slowly than its rodent counterpart in RNA mobility shift assays. The human Alu RNA-binding protein (RBP) is expressed after transfection of this cDNA into mouse cells. Expression of human RBP in rodent x human somatic cell hybrids is associated with substantial increase in endogenous small cytoplasmic Alu and scB1 transcripts but not other small RNAs. These studies provide evidence that this RBP associates with Alu transcripts in vivo and affects their metabolism and suggests a role for Alu transcripts in translation in an SRP-like manner. Analysis of hybrid lines indicated that the Alu RBP gene maps to human chromosome 15q22, which was confirmed by Southern blotting. The possibility that the primate-specific structure of this protein may have contributed to Alu evolution is considered. PMID- 8196636 TI - A strand bias occurs in point mutations associated with variant surface glycoprotein gene conversion in Trypanosoma rhodesiense. AB - We previously described a bloodstream Trypansoma rhodesiense clone, MVAT5-Rx2, whose isolation was based on its cross-reactivity with a monoclonal antibody (MAb) directed against a metacyclic variant surface glycoprotein (VSG). When the duplicated, expressed VSG gene in MVAT5-Rx2 was compared with its donor (basic copy) gene, 11 nucleotide differences were found in the respective 1.5-kb coding regions (Y. Lu, T. Hall, L. S. Gay, and J. E. Donelson, Cell 72:397-406, 1993). Here we describe a characterization of two additional bloodstream trypanosome clones, MVAT5-Rx1 and MVAT5-Rx3, whose VSGs are expressed from duplicated copies of the same donor VSG gene. The three trypanosome clones each react with the MVAT5-specific MAb, but they have different cross-reactivities with a panel of other MAbs, suggesting that their surface epitopes are similar but nonidentical. Each of the three gene duplication events occurs at a different 5' crossover site within a 76-bp repeat and is associated with a different set of point mutations. The 35, 11, and 28 point mutations in the duplicated VSG coding regions of Rx1, Rx2, and Rx3, respectively, exhibit a strand bias. In the sense strand, of the 74 total mutations generated in the three duplications, 54% are A-to-G or G-to-A (A:G) transitions and 7% are C:T transitions, while 26% are C:A transversions and 13% are C:G transversions. No T:G or T:A transversions occurred. Possible models for the generation of these point mutations are discussed. PMID- 8196635 TI - Presence of negative and positive cis-acting RNA splicing elements within and flanking the first tat coding exon of human immunodeficiency virus type 1. AB - The human immunodeficiency virus type 1 (HIV-1) RNA follows a complex splicing pathway in which a single primary transcript either remains unspliced or is alternatively spliced to more than 30 different singly and multiply spliced mRNAs. We have used an in vitro splicing assay to identify cis elements within the viral genome that regulate HIV-1 RNA splicing. A novel splicing regulatory element (SRE) within the first tat coding exon has been detected. This element specifically inhibits splicing at the upstream 3' splice site flanking this tat exon. The element only functions when in the sense orientation and is position dependent when inserted downstream of a heterologous 3' splice site. In vivo, an HIV-1 SRE mutant demonstrated a decrease in unspliced viral RNA, increased levels of single- and double-spliced tat mRNA, and reduced levels of env and rev mRNAs. In addition to the negative cis-acting SRE, the flanking 5' splice site downstream of the first tat coding exon acts positively to increase splicing at the upstream 3' splice sites. These results are consistent with hypotheses of bridging interactions between cellular factors that bind to the 5' splice site and those that bind at the upstream 3' splice site. PMID- 8196637 TI - Constitutive NF-kappa B activity in neurons. AB - NF-kappa B is inducible transcription factor present in many cell types in a latent cytoplasmic form. So far, only immune cells including mature B cells, thymocytes, and adherent macrophages have been reported to contain constitutively active forms of NF-kappa B in the nucleus. A recent study showed that the human immunodeficiency virus type 1 (HIV-1) promoter is highly active in several brain regions of transgenic mice (J. R. Corboy, J. M. Buzy, M. C. Zink, and J. E. Clements, Science 258:1804-1807, 1992). Since the activity of this viral enhancer is governed mainly by two binding sites for NF-kappa B, we were prompted to investigate the state of NF-kappa B activity in neurons. Primary neuronal cultures derived from rat hippocampus and cerebral cortex showed a high constitutive expression of an HIV-1 long terminal repeat-driven luciferase reporter gene, which was primarily dependent on intact NF-kappa B binding sites and was abolished upon coexpression of the NF-kappa B-specific inhibitor I kappa B-alpha. Indirect immunofluorescence and confocal laser microscopy showed that the activity of NF-kappa B correlated with the presence of the NF-kappa B subunits p50 and RelA (p65) in nuclei of cultured neurons. NF-kappa B was also constitutively active in neurons in vivo. As investigated by electrophoretic mobility shift assays, constitutive NF-kappa B DNA-binding activity was highly enriched in fractions containing neuronal nuclei prepared from rat cerebral cortex. Nuclear NF-kappa B-specific immunostaining was also seen in cryosections from mouse cerebral cortex and hippocampus. Only a subset of neurons was stained. Activated NF-kappa B in the brain is likely to participate in normal brain function and to reflect a distinct state of neuronal activity or differentiation. Furthermore, it may explain the high level of activity of the HIV-1 enhancer in neurons, an observation potentially relevant for the etiology of the AIDS dementia complex caused by HIV infection of the central nervous system. PMID- 8196640 TI - The CRY1 gene in Chlamydomonas reinhardtii: structure and use as a dominant selectable marker for nuclear transformation. AB - We have cloned and sequenced the CRY1 gene, encoding ribosomal protein S14 in Chlamydomonas reinhardtii, and found that it is highly similar to S14/rp59 proteins from other organisms, including mammals, Drosophila melanogaster, and Saccharomyces cerevisiae. We isolated a mutant strain resistant to the eukaryotic translational inhibitors cryptopleurine and emetine in which the resistance was due to a missense mutation (CRY1-1) in the CRY1 gene; resistance was dominant in heterozygous stable diploids. Cotransformation experiments using the CRY1-1 gene and the gene for nitrate reductase (NIT1) produced a low level of resistance to cryptopleurine and emetine. Resistance levels were increased when the CRY1-1 gene was placed under the control of a constitutive promoter from the ribulose bisphosphate carboxylase/oxygenase small subunit 2 (RBCS2) gene. We also found that the 5' untranslated region of the CRY1 gene was required for expression of the CRY1-1 transgene. Direct selection of emetine-resistant transformants was possible when transformed cells were first induced to differentiate into gametes by nitrogen starvation and then allowed to dedifferentiate back to vegetative cells before emetine selection was applied. With this transformation protocol, the RBCS2/CRY1-1 dominant selectable marker gene is a powerful tool for many molecular genetic applications in C. reinhardtii. PMID- 8196639 TI - Nucleosomal location of the STE6 TATA box and Mat alpha 2p-mediated repression. AB - It has been proposed that yeast MATa cell-specific genes are repressed in MAT alpha cells by the Mat alpha 2p repressor-directed placement of a nucleosome in a position that incorporates the TATA box of the MATa-specific gene close to the nucleosomal pseudodyad. In this study, we address this proposal directly with a series of plasmids designed to place the MATa-specific STE6 TATA box at different locations in a nucleosome and in the internucleosomal linker. These plasmids contain different lengths of synthetic random DNA between the Mat alpha 2p operator and the TATA box of the STE6 promoter, which is located upstream of a lacZ reporter gene in a multicopy plasmid. We show that in MAT alpha cells, a nucleosome is retained in an identical translational frame relative to the Mat alpha 2p operator in all the constructs investigated, irrespective of the sequence of the DNA wrapped onto the histone octamer. This result shows that the nucleosomal organization of the STE6 promoter in MAT alpha cells is not conferred by the sequence of the promoter itself. No expression of the lacZ reporter gene was detectable in MAT alpha cells in any of the constructs, even with the TATA box located in a short internucleosomal linker. These data indicate that repression of MATa-specific genes in MAT alpha cells does not require the precise translational placement of the TATA box close to the nucleosomal pseudodyad; the gene remains repressed when the TATA box is located within the investigated 250 bp region in the organized chromatin domain abutting the Mat alpha 2p operator in MAT alpha cells and may remain repressed with the TATA box located anywhere within this organized repression domain. PMID- 8196641 TI - The Drosophila tissue-specific factor Grainyhead contains novel DNA-binding and dimerization domains which are conserved in the human protein CP2. AB - We have mapped the regions in the Drosophila melanogaster tissue-specific transcription factor Grainyhead that are required for DNA binding and dimerization. These functional domains correspond to regions conserved between Grainyhead and the vertebrate transcription factor CP2, which we show has similar activities. The identified DNA-binding domain is large (263 amino acids) but contains a smaller core that is able to interact with DNA at approximately 400 fold lower affinity. The major dimerization domain is located in a separate region of the protein and is required to stabilize the interactions with DNA. Our data also suggest that Grainyhead activity can be modulated by an N-terminal inhibitory domain. PMID- 8196643 TI - Processing of truncated mouse or human rRNA transcribed from ribosomal minigenes transfected into mouse cells. AB - The processing of pre-rRNA in eukaryotic cells involves a complex pattern of nucleolytic reactions taking place in preribosomes with the participation of several nonribosomal proteins and small nuclear RNAs. The mechanism of these reactions remains largely unknown, mainly because of the absence of faithful in vitro assays for most processing steps. We have developed a pre-rRNA processing system using the transient expression of ribosomal minigenes transfected into cultured mouse cells. Truncated mouse or human rRNA genes are faithfully transcribed under the control of mouse promoter and terminator signals. The fate of these transcripts is analyzed by the use of reporter sequences flanking the rRNA gene inserts. Both mouse and human transcripts, containing the 3' end of 18S rRNA-encoding DNA (rDNA), internal transcribed spacer (ITS) 1, 5.8S rDNA, ITS 2, and the 5' end of 28S rDNA, are processed predominantly to molecules coterminal with the natural mature rRNAs plus minor products corresponding to cleavages within ITS 1 and ITS 2. To delineate cis-acting signals in pre-rRNA processing, we studied series of more truncated human-mouse minigenes. A faithful processing at the 18S rRNA/ITS 1 junction can be observed with transcripts containing only the 60 3'-terminal nucleotides of 18S rRNA and the 533 proximal nucleotides of ITS 1. However, further truncation of 18S rRNA (to 8 nucleotides) or of ITS 1 (to 48 nucleotides) abolishes the cleavage of the transcript. Processing at the ITS 2/28S rRNA junction is observed with truncated transcripts lacking the 5.8S rRNA plus a major part of ITS 2 and containing only 502 nucleotides of 28S rRNA. However, further truncation of the 28S rRNA segment to 217 nucleotides abolishes processing. Minigene transcripts containing most internal sequences of either ITS 1 or ITS 2, but devoid of ITS/mature rRNA junctions, are not processed, suggesting that the cleavages in vivo within either ITS segment are dependent on the presence in cis of mature rRNA sequences. These results show that the major cis signals for pre-rRNA processing at the 18S rRNA/ITS 1 or the ITS2/28S rRNA junction involve solely a limited critical length of the respective mature rRNA and adjacent spacer sequences. PMID- 8196638 TI - Human replication protein A binds single-stranded DNA in two distinct complexes. AB - Human replication protein A, a single-stranded DNA (ssDNA)-binding protein, is a required factor in eukaryotic DNA replication and DNA repair systems and has been suggested to function during DNA recombination. The protein is also a target of interaction for a variety of proteins that control replication, transcription, and cell growth. To understand the role of hRPA in these processes, we examined the binding of hRPA to defined ssDNA molecules. Employing gel shift assays that "titrated" the length of ssDNA, hRPA was found to form distinct multimeric complexes that could be detected by glutaraldehyde cross-linking. Within these complexes, monomers of hRPA utilized a minimum binding site size on ssDNA of 8 to 10 nucleotides (the hRPA8-10nt complex) and appeared to bind ssDNA cooperatively. Intriguingly, alteration of gel shift conditions revealed the formation of a second, distinctly different complex that bound ssDNA in roughly 30-nucleotide steps (the hRPA30nt complex), a complex similar to that described by Kim et al. (C. Kim, R. O. Snyder, and M. S. Wold, Mol. Cell. Biol. 12:3050-3059, 1992). Both the hRPA8-10nt and hRPA30nt complexes can coexist in solution. We speculate that the role of hRPA in DNA metabolism may be modulated through the ability of hRPA to bind ssDNA in these two modes. PMID- 8196642 TI - Repression of cyclin D1: a novel function of MYC. AB - Constitutive expression of human MYC represses mRNA levels of cyclin D1 in proliferating BALB/c-3T3 fibroblasts. We expressed a series of mutant alleles of MYC and found that downregulation of cyclin D1 is distinct from previously described properties of MYC. In particular, we found that association with Max is not required for repression of cyclin D1 by MYC in vivo. Conversely, the integrity of a small amino-terminal region (amino acids 92 to 106) of MYC is critical for repression of cyclin D1 but dispensable for transformation of established RAT1A cells. Runoff transcription assays showed that repression occurs at the level of transcription initiation. We cloned the promoter of the gene for human cyclin D1 and found that it lacks a canonical TATA element. Transcription starts at an initiator element similar to that of the adenovirus major late promoter; this element can be directly bound by USF in vitro. Expression of MYC represses the cyclin D1 promoter via core promoter elements and antagonizes USF-mediated transactivation. Taken together, our data define a new pathway for gene regulation by MYC and show that the cyclin D1 gene is a target gene for repression by MYC. PMID- 8196645 TI - The insulin gene contains multiple transcriptional elements that respond to glucose. AB - The beta cells in the pancreatic islets of Langerhans increase insulin gene transcription in response to increased glucose concentration. We have mapped sequences within the rat insulin I gene 5'-flanking DNA (rInsI promoter) that direct this transcriptional response to glucose. When linked to chloramphenicol acetyltransferase and expressed in cultured beta cells, no single mutation of the rInsI promoter removes its ability to respond to glucose, although several mutations cause marked reductions in basal chloramphenicol acetyltransferase expression. A 50-bp sequence isolated from the rInsI promoter, the Far-FLAT minienhancer, can confer glucose responsiveness to nonresponsive promoters. Fine mapping of this minienhancer further localizes a glucose response to the sequence GGCCATCTGGCC, or the Far element. Nuclear extracts from islets grown in various glucose concentrations demonstrate a glucose-stimulated increase in a protein complex that binds the Far element and contains the transcription factors Pan-1 and Pan-2. Overexpression of intact or partially deleted Pan-1 ablates the Far directed transcriptional response to glucose. We conclude that the full glucose response of the insulin promoter involves the interaction of multiple sequence elements. Part of this response, however, results from activation of a complex binding at the Far element. PMID- 8196644 TI - Mapping and mutagenesis of the amino-terminal transcriptional repression domain of the Drosophila Kruppel protein. AB - We previously demonstrated that the Drosophila Kruppel protein is a transcriptional repressor with separable DNA-binding and transcriptional repression activities. In this study, the minimal amino (N)-terminal repression region of the Kruppel protein was defined by transferring regions of the Kruppel protein to a heterologous DNA-binding protein, the lacI protein. Fusion of a predicted alpha-helical region from amino acids 62 to 92 in the N terminus of the Kruppel protein was sufficient to transfer repression activity. This putative alpha-helix has several hydrophobic surfaces, as well as a glutamine-rich surface. Mutants containing multiple amino acid substitutions of the glutamine residues demonstrated that this putative alpha-helical region is essential for repression activity of a Kruppel protein containing the entire N-terminal and DNA binding regions. Furthermore, one point mutant with only a single glutamine on this surface altered to lysine abolished the ability of the Kruppel protein to repress, indicating the importance of the amino acid at residue 86 for repression. The N terminus also contained an adjacent activation region localized between amino acids 86 and 117. Finally, in accordance with predictions from primary amino acid sequence similarity, a repression region from the Drosophila even-skipped protein, which was six times more potent than that of the Kruppel protein in the mammalian cells, was characterized. This segment included a hydrophobic stretch of 11 consecutive alanine residues and a proline-rich region. PMID- 8196648 TI - Differential binding of c-Myc and Max to nucleosomal DNA. AB - The ability of a transcription factor to function in vivo must be determined in part by its ability to bind to its recognition site in chromatin. We have used Max and derivatives of c-Myc to characterize the effect of changes of dimerization partner on binding to nucleosomal DNA templates. We find that homo- and heterodimeric complexes of these proteins bind to the CACGTG sequence in free DNA with similar affinities. Although Max homodimers bind to nucleosomes, truncated c-Myc homodimers do not. Surprisingly, modifying the c-Myc dimerization interface or changing its dimerization partner to Max enables nucleosomal DNA binding. Thus, changes in dimer structure or dimerization efficiency can have significant effects on nucleosome binding that are not predicted from their affinity for free DNA. We conclude that domains other than the basic region per se influence the ability of a transcription factor to bind to nucleosomal DNA and that changes of dimerization partner can directly affect the ability of a factor to occupy nucleosomal binding sites. PMID- 8196646 TI - An amino-terminal tetrapeptide specifies cotranslational degradation of beta tubulin but not alpha-tubulin mRNAs. AB - The steady-state level of alpha- and beta-tubulin synthesis is autoregulated by a posttranscriptional mechanism that selectively alters alpha- and beta-tubulin mRNA levels in response to changes in the unassembled tubulin subunit concentration. For beta-tubulin mRNAs, previous efforts have shown that this is the result of a selective mRNA degradation mechanism which involves cotranslational recognition of the nascent amino-terminal beta-tubulin tetrapeptide as it emerges from the ribosome. Site-directed mutagenesis is now used to determine that the minimal sequence requirement for conferring the full range of beta-tubulin autoregulation is the amino-terminal tetrapeptide MR(E/D)I. Although tubulin-dependent changes in alpha-tubulin mRNA levels are shown to result from changes in cytoplasmic mRNA stability, transfection of wild-type and mutated alpha-tubulin genes reveals that alpha- and beta-tubulin mRNA degradation is not mediated through a common pathway. Not only does the amino-terminal alpha tubulin tetrapeptide MREC fail to confer regulated mRNA degradation, neither wild type alpha-tubulin transgenes nor an alpha-tubulin gene mutated to encode an amino-terminal MREI yields mRNAs that are autoregulated. Further, although slowing ribosome transit accelerates the autoregulated degradation of endogenous alpha- and beta-tubulin mRNAs, degradation of alpha-tubulin transgene mRNAs is not enhanced, and in one case, the mRNA is actually stabilized. We conclude that, despite similarities, alpha- and beta-tubulin mRNA destabilization pathways utilize divergent determinants to link RNA instability to tubulin subunit concentrations. PMID- 8196647 TI - Pan/E2A expression precedes immunoglobulin heavy-chain expression during B lymphopoiesis in nontransformed cells, and Pan/E2A proteins are not detected in myeloid cells. AB - A newly developed rat long-term bone marrow culture system was used to study the role of Pan/E2A basic helix-loop-helix transcription factors during B-cell development. In this system, B-lymphocyte progenitors actively differentiate into mature B cells. Monoclonal (Yae) and polyclonal (anti-Pan) antibodies were employed to characterize the expression of Pan proteins by Western blot assay during hematopoiesis and to examine the components of immunoglobulin heavy-chain gene enhancer element-binding species by electrophoretic mobility shift assay. During B-cell development, the appearance of Pan/E2A proteins preceded the expression of immunoglobulin heavy-chain protein. A Pan-containing immunoglobulin heavy-chain enhancer element (mu E5)-binding species (BCF1), composed of immunoreactive Pan-1/E47 but not Pan-2/E12, was observed concomitantly with the detection of Pan/E2A proteins. In addition to BCF1, other mu E5-binding species were detected which were not recognized by the Yae antibody. Two of these species were present in primary B-lymphocyte and myeloid cultures and were recognized by an anti-upstream stimulatory factor antiserum. Although Pan/E2A proteins have been proposed to be ubiquitous, Pan/E2A proteins were not detected in primary myeloid cultures composed mainly of granulocytes and macrophages or in the macrophage cell line J774. The absence of Pan/E2A proteins in differentiated myeloid cells correlated with low steady-state levels of Pan/E2A RNA. However, Pan/E2A proteins were present in a promyeloid cell line, 32DCL3, suggesting that extinction of Pan/E2A expression may play a role in myelopoiesis. PMID- 8196649 TI - Aberrant function of the Ras-related protein TC21/R-Ras2 triggers malignant transformation. AB - Although the human Ras proteins are members of a large superfamily of Ras-related proteins, to date, only the proteins encoded by the three mammalian ras genes have been found to possess oncogenic potential. Among the known Ras-related proteins, TC21/R-Ras2 exhibits the most significant amino acid identity (55%) to Ras proteins. We have generated mutant forms of TC21 that possess amino acid substitutions analogous to those that activate Ras oncogenic potential [designated TC21(22V) and TC21(71L)] and compared the biological properties of TC21 with those of Ras proteins in NIH 3T3 and Rat-1 transformation assays. Whereas wild-type TC21 did not show any transforming potential in vitro, both TC21(22V) and TC21(71L) displayed surprisingly potent transforming activities that were comparable to the strong transforming activity of oncogenic Ras proteins. Like Ras-transformed cells, NIH 3T3 cells expressing mutant TC21 proteins formed foci of morphologically transformed cells in monolayer cultures, proliferated in low serum, formed colonies in soft agar, and developed progressive tumors in nude mice. Thus, TC21 is the first Ras-related protein to exhibit potent transforming activity equivalent to that of Ras. Furthermore, mutant TC21 proteins also stimulated constitutive activation of mitogen-activated protein kinases as well as transcriptional activation from Ras-responsive promoter elements (Ets/AP-1 and NF-kappa B). We conclude that aberrant TC21 function may trigger cellular transformation via a signal transduction pathway similar to that of oncogenic Ras and suggest that deregulated TC21 activity may contribute significantly to human oncogenesis. PMID- 8196650 TI - Mutational analysis of ERCC3, which is involved in DNA repair and transcription initiation: identification of domains essential for the DNA repair function. AB - The human ERCC3 gene, which corrects specifically the nucleotide excision repair defect in human xeroderma pigmentosum group B and cross-complements the repair deficiency in rodent UV-sensitive mutants of group 3, encodes a presumed DNA helicase that is identical to the p89 subunit of the general transcription factor TFIIH/BTF2. To examine the significance of the postulated functional domains in ERCC3, we have introduced mutations in the ERCC3 cDNA by means of site-specific mutagenesis and have determined the repair capacity of each mutant to complement the UV-sensitive phenotype of rodent group 3 cells. A conservative substitution of arginine for the invariant lysine residue in the ATPase motif (helicase domain I), six deletion mutations in the other helicase domains, and a deletion in the potential helix-turn-helix DNA-binding motif fail to complement the ERCC3 excision repair defect of rodent group 3 mutants, which implies that the helicase domains as well as the potential DNA-binding motif are required for the repair function of ERCC3. Analysis of carboxy-terminal deletions suggests that the carboxy-terminal exon may comprise a distinct determinant for the DNA repair function. In addition, we show that a functional epitope-tagged version of ERCC3 accumulates in the nucleus. Deletion of the putative nuclear location signal impairs neither the nuclear location nor the repair function, indicating that other sequences may (also) be involved in translocation of ERCC3 to the nucleus. PMID- 8196651 TI - GPD1, which encodes glycerol-3-phosphate dehydrogenase, is essential for growth under osmotic stress in Saccharomyces cerevisiae, and its expression is regulated by the high-osmolarity glycerol response pathway. AB - The yeast Saccharomyces cerevisiae responds to osmotic stress, i.e., an increase in osmolarity of the growth medium, by enhanced production and intracellular accumulation of glycerol as a compatible solute. We have cloned a gene encoding the key enzyme of glycerol synthesis, the NADH-dependent cytosolic glycerol-3 phosphate dehydrogenase, and we named it GPD1. gpd1 delta mutants produced very little glycerol, and they were sensitive to osmotic stress. Thus, glycerol production is indeed essential for the growth of yeast cells during reduced water availability. hog1 delta mutants lacking a protein kinase involved in osmostress induced signal transduction (the high-osmolarity glycerol response [HOG] pathway) failed to increase glycerol-3-phosphate dehydrogenase activity and mRNA levels when osmotic stress was imposed. Thus, expression of GPD1 is regulated through the HOG pathway. However, there may be Hog1-independent mechanisms mediating osmostress-induced glycerol accumulation, since a hog1 delta strain could still enhance its glycerol content, although less than the wild type. hog1 delta mutants are more sensitive to osmotic stress than isogenic gpd1 delta strains, and gpd1 delta hog1 delta double mutants are even more sensitive than either single mutant. Thus, the HOG pathway most probably has additional targets in the mechanism of adaptation to hypertonic medium. PMID- 8196652 TI - A novel basic helix-loop-helix protein is expressed in muscle attachment sites of the Drosophila epidermis. AB - We have found that a novel basic helix-loop-helix (bHLH) protein is expressed almost exclusively in the epidermal attachments sites for the somatic muscles of Drosophila melanogaster. A Drosophila cDNA library was screened with radioactively labeled E12 protein, which can dimerize with many HLH proteins. One clone that emerged from this screen encoded a previously unknown protein of 360 amino acids, named delilah, that contains both basic and HLH domains, similar to a group of cellular transcription factors implicated in cell type determination. Delilah protein formed heterodimers with E12 that bind to the muscle creatine kinase promoter. In situ hybridization with the delilah cDNA localized the expression of the gene to a subset of cells in the epidermis which form a distinct pattern involving both the segmental boundaries and intrasegmental clusters. This pattern was coincident with the known sites of attachment of the somatic muscles to tendon cells in the epidermis. delilah expression persists in snail mutant embryos which lack mesoderm, indicating that expression of the gene was not induced by attachment of the underlying muscles. The similarity of this gene to other bHLH genes suggests that it plays an important role in the differentiation of epidermal cells into muscle attachment sites. PMID- 8196653 TI - Functional substitution of an essential yeast RNA polymerase subunit by a highly conserved mammalian counterpart. AB - We isolated the cDNA encoding the homolog of the Saccharomyces cerevisiae nuclear RNA polymerase common subunit RPB6 from hamster CHO cells. Alignment of yeast RPB6 with its mammalian counterpart revealed that the subunits have nearly identical carboxy-terminal halves and a short acidic region at the amino terminus. Remarkably, the length and amino acid sequence of the hamster RPB6 are identical to those of the human RPB6 subunit. The conservation in sequence from lower to higher eukaryotes also reflects conservation of function in vivo, since hamster RPB6 supports normal wild-type yeast cell growth in the absence of the essential gene encoding RPB6. PMID- 8196654 TI - m3G cap hypermethylation of U1 small nuclear ribonucleoprotein (snRNP) in vitro: evidence that the U1 small nuclear RNA-(guanosine-N2)-methyltransferase is a non snRNP cytoplasmic protein that requires a binding site on the Sm core domain. AB - The RNA components of small nuclear ribonucleoproteins (U snRNPs) possess a characteristic 5'-terminal trimethylguanosine cap structure (m3G cap). This cap is an important component of the nuclear localization signal of U snRNPs. It arises by hypermethylation of a cotranscriptionally added m7G cap. Here we describe an in vitro assay for the hypermethylation, which employs U snRNP particles reconstituted in vitro from purified components and subsequent analysis by m3G cap-specific immunoprecipitation. Complementation studies in vitro revealed that both cytosol and S-adenosylmethionine are required for the hypermethylation of an m7G-capped U1 snRNP reconstituted in vitro, indicating that the U1 snRNA-(guanosine-N2)-methyltransferase is a trans-active non-snRNP protein. Chemical modification revealed one cytoplasmic component required for hypermethylation and one located on the snRNP: these components have different patterns of sensitivity to modification by N-ethylmaleimide and iodoacetic acid (IAA). In the presence of cytosol and S-adenosylmethionine, an intact Sm core domain is a necessary and sufficient substrate for cap hypermethylation. These data, together with our observation that isolated native U1 snRNPs but not naked U1 RNA inhibit the trimethylation of in vitro-reconstituted U1 snRNP, indicate that the Sm core binds the methyltransferase specifically. Moreover, isolated native U2 snRNP also inhibits trimethylation of U1 snRNP, suggesting that other Sm-class U snRNPs might share the same methyltransferase. IAA modification of m7G capped U1 snRNPs inhibited hypermethylation when they were microinjected into Xenopus oocytes and consequently also inhibited nuclear import. In contrast, modification with IAA of m3G-capped U1 snRNPs reconstituted in vitro did not interfere with their nuclear transport in oocytes. These data suggest that m3G cap formation and nuclear transport of U1 snRNPs are mediated by distinct factors, which require distinct binding sites on the Sm core of U1 snRNP. PMID- 8196655 TI - Homologous recombination of monkey alpha-satellite repeats in an in vitro simian virus 40 replication system: possible association of recombination with DNA replication. AB - To study homologous recombination between repeated sequences in an in vitro simian virus 40 (SV40) replication system, we constructed a series of substrate DNAs that contain two identical fragments of monkey alpha-satellite repeats. Together with the SV40-pBR322 composite vector encoding Apr and Kmr, the DNAs also contain the Escherichia coli galactokinase gene (galK) positioned between two alpha-satellite fragments. The alpha-satellite sequence used consists of multiple units of tandem 172-bp sequences which differ by microheterogeneity. The substrate DNAs were incubated in an in vitro SV40 DNA replication system and used to transform the E. coli galK strain DH10B after digestion with DpnI. The number of E. coli galK Apr Kmr colonies which contain recombinant DNAs were determined, and their structures were analyzed. Products of equal and unequal crossovers between identical 172-bp sequences and between similar but not identical (homeologous) 172-bp sequences, respectively, were detected, although those of the equal crossover were predominant among all of the galK mutant recombinants. Similar products were also observed in the in vivo experiments with COS1 cells. The in vitro experiments showed that these recombinations were dependent on the presence of both the SV40 origin of DNA replication and SV40 large T antigen. Most of the recombinant DNAs were generated from newly synthesized DpnI-resistant DNAs. These results suggest that the homologous recombination observed in this SV40 system is associated with DNA replication and is suppressed by mismatches in heteroduplexes formed between similar but not identical sequences. PMID- 8196656 TI - Apoptosis in erythroid progenitors deprived of erythropoietin occurs during the G1 and S phases of the cell cycle without growth arrest or stabilization of wild type p53. AB - Erythropoietin (Epo) inhibits apoptosis in murine proerythroblasts infected with the anemia-inducing strain of Friend virus (FVA cells). We have shown that the apoptotic process in FVA cell populations deprived of Epo is asynchronous as a result of a heterogeneity in Epo dependence among individual cells. Here we investigated whether apoptosis in FVA cells correlated with cell cycle phase or stabilization of p53 tumor suppressor protein. DNA analysis in nonapoptotic FVA cell subpopulations cultured without Epo demonstrated little change in the percentages of cells in G1,S, and G2/M phases over time. Analysis of the apoptotic subpopulation revealed high percentages of cells in G1 and S, with few cells in G2/M at any time. When cells were sorted from G1 and S phases prior to culture without Epo, apoptotic cells appeared at the same rate in both populations, indicating that no prior commitment step had occurred in either G1 or S phase. Steady-state wild-type p53 protein levels were very low in FVA cells compared with control cell lines and did not accumulate in Epo-deprived cultures; however, p53 protein did accumulate when FVA cells were treated with the DNA damaging agent actinomycin D. These data indicate that erythroblast apoptosis caused by Epo deprivation (i) occurs throughout G1 and S phases and does not require cell cycle arrest, (ii) does not have a commitment event related to cell cycle phase, and (iii) is not associated with conformational changes or stabilization of wild-type p53 protein. PMID- 8196657 TI - Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton. AB - A potent and specific small molecule inhibitor of farnesyl-protein transferase, L 739,749, caused rapid morphological reversion and growth inhibition of ras transformed fibroblasts (Rat1/ras cells). Morphological reversion occurred within 18 h of L-739,749 addition. The reverted phenotype was stable for several days in the absence of inhibitor before the transformed phenotype reappeared. Cell enlargement and actin stress fiber formation accompanied treatment of both Rat1/ras and normal Rat1 cells. Significantly, inhibition of Ras processing did not correlate with the initiation or maintenance of the reverted phenotype. While a single treatment with L-739,749 was sufficient to morphologically revert Rat1/ras cells, repetitive inhibitor treatment was required to significantly reduce cell growth rate. Thus, the effects of L-739,749 on transformed cell morphology and cytoskeletal actin organization could be separated from effects on cell growth, depending on whether exposure to a farnesyl-protein transferase inhibitor was transient or repetitive. In contrast, L-739,749 had no effect on the growth, morphology, or actin organization of v-raf-transformed cells. Taken together, the results suggest that the mechanism of morphological reversion is complex and may involve farnesylated proteins that control the organization of cytoskeletal actin. PMID- 8196658 TI - An rRNA variable region has an evolutionarily conserved essential role despite sequence divergence. AB - Regions extremely variable in size and sequence occur at conserved locations in eukaryotic rRNAs. The functional importance of one such region was determined by gene reconstruction and replacement in Tetrahymena thermophila. Deletion of the D8 region of the large-subunit rRNA inactivates T. thermophila rRNA genes (rDNA): transformants containing only this type of rDNA are unable to grow. Replacement with an unrelated sequence of similar size or a variable region from a different position in the rRNA also inactivated the rDNA. Mutant rRNAs resulting from such constructs were present only in precursor forms, suggesting that these rRNAs are deficient in either processing or stabilization of the mature form. Replacement with D8 regions from three other organisms restored function, even though the sequences are very different. Thus, these D8 regions share an essential functional feature that is not reflected in their primary sequences. Similar tertiary structures may be the quality these sequences share that allows them to function interchangeably. PMID- 8196660 TI - Ubiquitous and tenacious methylation of the CpG site in codon 248 of the p53 gene may explain its frequent appearance as a mutational hot spot in human cancer. AB - Cytosine methylation at CpG dinucleotides is thought to cause more than one-third of all transition mutations responsible for human genetic diseases and cancer. We investigated the methylation status of the CpG dinucleotide at codon 248 in exon 7 of the p53 gene because this codon is a hot spot for inactivating mutations in the germ line and in most human somatic tissues examined. Codon 248 is contained within an HpaII site (CCGG), and the methylation status of this and flanking CpG sites was analyzed by using the methylation-sensitive enzymes CfoI (GCGC) and HpaII. Codon 248 and the CfoI and HpaII sites in the flanking introns were methylated in every tissue and cell line examined, indicating extensive methylation of this region in the p53 gene. Exhaustive treatment of an osteogenic sarcoma cell line, TE85, with the hypomethylating drug 5-aza-2'-deoxycytidine did not demethylate codon 248 or the CfoI sites in intron 6, although considerable global demethylation of the p53 gene was induced. Constructs containing either exon 7 alone or exon 7 and the flanking introns were transfected into TE85 cells to determine whether de novo methylation would occur. The presence of exon 7 alone caused some de novo methylation to occur at codon 248. More extensive de novo methylation of the CfoI sites in intron 6, which contains an Alu sequence, occurred in cells transfected with a vector containing exon 7 and flanking introns. With longer time in culture, there was increased methylation at the CfoI sites, and de novo methylation of codon 248 and its flanking HpaII sites was observed. These de novo-methylated sites were also resistant to 5-aza-2' deoxycytidine-induced demethylation. The frequent methylation of codon 248 and adjacent Alu sequence may explain the enhanced mutability of this site as a result of the deamination of the 5-methylcytosine. PMID- 8196659 TI - Effects of mutant Ran/TC4 proteins on cell cycle progression. AB - Ran/TC4, a member of the RAS gene superfamily, encodes an abundant nuclear protein that binds and hydrolyzes GTP. Transient expression of a Ran/TC4 mutant protein deficient in GTP hydrolysis blocked DNA replication, suggesting a role for Ran/TC4 in the regulation of cell cycle progression. To test this possibility, we exploited an efficient transfection system, involving the introduction of cDNAs in the pMT2 vector into 293/Tag cells, to analyze phenotypes associated with mutant and wild-type Ran/TC4 expression. Expression of a Ran/TC4 mutant protein deficient in GTP hydrolysis inhibited proliferation of transfected cells by arresting them predominantly in the G2, but also in the G1, phase of the cell cycle. Deletion of an acidic carboxy-terminal hexapeptide from the Ran/TC4 mutant did not alter its nuclear localization but did block its inhibitory effect on cell cycle progression. These data suggest that normal progression of the cell cycle is coupled to the operation of a Ran/TC4 GTPase cycle. Mediators of this coupling are likely to include the nuclear regulator of chromosome condensation 1 protein and the mitosis-promoting factor complex. PMID- 8196661 TI - The human cut homeodomain protein represses transcription from the c-myc promoter. AB - Studies of the c-myc promoter have shown that efficient transcription initiation at the P2 start site as well as the block to elongation of transcription require the presence of the ME1a1 protein binding site upstream of the P2 TATA box. Following fractionation by size exclusion chromatography, three protein-ME1a1 DNA complexes, a, b, and c, were detected by electrophoretic mobility shift assay. A cDNA encoding a protein present in complex c was isolated by screening of an expression library with an ME1a1 DNA probe. This cDNA was found to encode the human homolog of the Drosophila Cut homeodomain protein. The bacterially expressed human Cut (hu-Cut) protein bound to the ME1a1 site, and antibodies against hu-Cut inhibited the ME1a1 binding activity c in nuclear extracts. In cotransfection experiments, the hu-Cut protein repressed transcription from the c myc promoter, and this repression was shown to be dependent on the presence of the ME1a1 site. Using a reporter construct with a heterologous promoter, we found that c-myc exon 1 sequences were also necessary, in addition to the ME1a1 site, for repression by Cut. Taken together, these results suggest that the human homolog of the Drosophila Cut homeodomain protein is involved in regulation of the c-myc gene. PMID- 8196662 TI - TATA-dependent enhancer stimulation of promoter activity in mice is developmentally acquired. AB - Herpes simplex virus (HSV) thymidine kinase (tk) promoter activity depends on four transcription factor binding sites, one of which is a TATA box sequence, and the presence of either a cis-acting enhancer sequence or a transactivator protein. Studies presented here show that this TATA box was required for promoter activity only after cells began to differentiate and then only when promoter activity was stimulated by either an enhancer or a transactivator. When the HSV tk promoter was utilized by mouse embryos from the one-cell to eight-cell stage of development or by undifferentiated mouse embryonic stem cells, disruption of the HSV tk TATA box by site-specific mutations did not reduce promoter activity. This was true even when HSV tk promoter activity was stimulated strongly by either the embryo-responsive polyomavirus F101 enhancer or its natural transactivator, the HSV ICP4 gene product. However, stimulated expression was dependent on a distal Sp1 DNA binding site. Similarly, disruption of the TATA box did not reduce tk promoter activity in primary mouse embryonic fibroblasts or in immortalized 3T3 mouse fibroblasts; in fact, promoter activity was increased up to 2.6-fold. However, in these differentiated cells, stimulation of the HSV tk promoter by either the F101 enhancer or ICP4 protein required the TATA box. HSV tk promoter activity also was dependent on its TATA box in the mouse oocyte, a terminally differentiated cell with an endogenous transactivating activity. These results reveal that the need for a TATA box is developmentally acquired and depends on at least two parameters: the differentiated state of the cell and stimulation of the promoter by either an enhancer or a transactivator. PMID- 8196663 TI - Heterokaryons of cardiac myocytes and fibroblasts reveal the lack of dominance of the cardiac muscle phenotype. AB - The molecular characterization of a cardiac determination gene has been an elusive goal for the past several years. Prior to cloning of the skeletal muscle determination factor MyoD, the presence of a dominantly acting skeletal muscle determination factor had been inferred from the observation that the skeletal muscle phenotype was dominant in skeletal muscle-fibroblast heterokaryons (H. M. Blau, G. K. Pavlath, E. C. Hardeman, C.-P. Chiu, L. Siberstein, S. G. Webster, S. C. Miller, and D. Webster, Science 230:758-766, 1985). In these experiments, we have examined cardiac-fibroblast heterokaryons to investigate the existence of a dominantly acting cardiac determination factor. We have employed a novel experimental approach using primary embryonic fibroblasts from transgenic mice as a means of assaying for the activation of a cardiac promoter-luciferase reporter transgene within fibroblast nuclei. This approach provides a potential means of genetic selection for a dominantly acting positive factor and can be generalized to other systems. We have examined the expression of three markers of the cardiac lineage: a myofibrillar protein promoter (MLC2), a secreted protein (ANF), and a transcription factor (MEF2). MEF2 is specific to both cardiac and skeletal muscle cells. Our results indicate that in a majority of heterokaryons with an equal ratio of cardiac to fibroblast nuclei, none of these cardiac markers are expressed, indicating that the cardiac phenotype is not dominant over the embryonic fibroblast phenotype. The distinction from previous results with skeletal muscle is emphasized by our results with MEF2, which is dominantly expressed in skeletal muscle-fibroblast but not cardiac-fibroblast heterokaryons, supporting its divergent regulation in the two cell types. PMID- 8196664 TI - The transforming growth factor beta type II receptor can replace the activin type II receptor in inducing mesoderm. AB - The type II receptors for the polypeptide growth factors transforming growth factor beta (TGF-beta) and activin belong to a new family of predicted serine/threonine protein kinases. In Xenopus embryos, the biological effects of activin and TGF-beta 1 are strikingly different; activin induces a full range of mesodermal cell types in the animal cap assay, while TGF-beta 1 has no effects, presumably because of the lack of functional TGF-beta receptors. In order to assess the biological activities of exogenously added TGF-beta 1, RNA encoding the TGF-beta type II receptor was introduced into Xenopus embryos. In animal caps from these embryos, TGF-beta 1 and activin show similar potencies for induction of mesoderm-specific mRNAs, and both elicit the same types of mesodermal tissues. In addition, the response of animal caps to TGF-beta 1, as well as to activin, is blocked by a dominant inhibitory ras mutant, p21(Asn-17)Ha-ras. These results indicate that the activin and TGF-beta type II receptors can couple to similar signalling pathways and that the biological specificities of these growth factors lie in their different ligand-binding domains and in different competences of the responding cells. PMID- 8196665 TI - GATA elements are necessary for the activity and tissue specificity of the T-cell receptor beta-chain transcriptional enhancer. AB - Three high-affinity binding sites for the GATA family of transcriptional regulators have been identified within the T-cell receptor beta-chain (TCR beta) transcriptional enhancer, and their functional significance has been determined in an effort to understand the T-cell specificity of the enhancer more fully. One site, TE4, is important for activity of the enhancer in T cells. Neither site TE1 nor site TE2 can functionally replace a mutated TE4 site in T cells; however, the same protein, probably GATA-3, binds all three sites, as judged by electrophoretic mobility shift, oligonucleotide competition, and proteolytic clipping assays. These data suggest that additional proteins are critical for the ability of GATA-3 to activate the TCR beta enhancer. In fibroblasts, the GATA sequence at site TE1 appears to bind a negative regulator. Since this is not true in B cells, B cells and fibroblasts appear to have different mechanisms for negative regulation of the TCR beta enhancer. PMID- 8196666 TI - Cell transformation by c-fos requires an extended period of expression and is independent of the cell cycle. AB - The proto-oncogene transcription factors Fos and Jun form a heterodimeric complex that binds to DNA and regulates expression of specific target genes. Continuous expression of c-fos causes transformation of cultured fibroblasts and induces osteogenic sarcoma in mice. To investigate the molecular basis of fos-mediated oncogenesis, we developed a conditional cell transformation system in which Fos expression was regulated by isopropyl-beta-D-thiogalactopyranoside (IPTG). Synthesis or repression of Fos in L1-3c-fos cells occurred rapidly, within 30 min, after the removal or addition of IPTG to the culture medium. However, there was a significant delay between the induction of Fos expression and the appearance of morphological transformation. No effect was observed after 12 h of Fos expression, partial transformation was detected after 24 h, and full transformation required approximately 3 days of continuous Fos expression. Similarly, the transformed cell morphology persisted for at least 2 days after repression of Fos, and a normal phenotype was observed only after 3 days. Fos-Jun complexes, capable of binding to AP-1 sequences, were present continuously during the delay in morphological transformation. Furthermore, increased expression of several candidate Fos target genes, including those encoding Fra-1, transin (stromelysin), collagenase, and ornithine decarboxylase, was detected shortly after Fos induction. The induction of morphological transformation was not dependent on the cell cycle, as it occurred in both cycling and noncycling cells. Thus, the Fos-Jun complexes present before L1-3c-fos cells become fully transformed are transcriptionally active. These complexes disappeared, and the Fos target genes were repressed at least 2 days prior to reversion. Our results suggest that cell transformation by Fos requires increased expression of a target gene(s) with a long-lived product(s) that must reach a critical level. PMID- 8196667 TI - Mutations that alter ligand-induced switches and dimerization activities in the retinoid X receptor. AB - The retinoid X receptor (RXR) heterodimerizes with a variety of nuclear receptors. In addition, RXR forms homodimers in the presence of its ligand, 9-cis retinoic acid. From deletion and point mutation analysis we present evidence that a short region (amino acids 413 to 443) in the carboxy terminus of RXR alpha is critical for both homo- and heterodimeric interactions as well as for diverse functional activities. In addition, we present evidence that homo- and heterodimer functions can be separated. The deletion of 19 amino acids from the C terminal end of RXR dramatically reduced the transcriptional activation function of RXR. The removal of 10 additional amino acids resulted in a receptor (delta RXR3) that had completely lost its ligand-dependent homodimer function but retained its heterodimer activities. Heterodimer function was abolished by the deletion of an additional 20 amino acids. Single amino acid substitutions in the region generated receptors with altered RXR homodimer DNA binding, while simultaneous mutation of three Leu residues (Leu-418, -419 and -422) completely abolished both RXR homodimer and heterodimer DNA binding activities. Mutation of Leu-430 to Phe (L430-F) resulted in a receptor that bound to DNA strongly as homodimers in a ligand-independent manner, while another single amino acid exchange (L422-Q) led to a mutant that behaved in a manner exactly opposite to that of wild-type RXR in that the homodimerization of the mutant occurred in the absence of ligand and was inhibited by 9-cis-retinoic acid. In transfection assays, both L422-Q and L430-F failed to act as homodimers but retained their heterodimer function. Our studies demonstrate the unique properties of the RXR ligand binding domain and point to specific residues that mediate homo- and heterodimer activities and ligand-induced conformational switches. PMID- 8196669 TI - Jacalin, a lectin with anti-HIV-1 properties, and HIV-1 gp120 envelope protein interact with distinct regions of the CD4 molecule. AB - Jacalin is a multimeric plant lectin able to interact with the lymphocyte cell surface molecule CD4, a known receptor for the human immunodeficiency virus type 1 (HIV-1). Moreover, jacalin is able to block HIV-1 infection of CD4+ lymphoblastoid cells. Here we studied whether jacalin prevents HIV-1 gp120-CD4 interactions. We found (i) that jacalin did not inhibit HIV-1 Lai-induced syncytium formation that requires gp120-CD4 interactions; (ii) that jacalin prevented neither rgp120 binding to cell-surface CD4 nor sCD4 binding to viral envelope proteins expressed at the surface of HIV-1-infected lymphoblastoid cells; (iii) that jacalin did not compete for binding to CD4 with anti-CD4 mAb specific for the CDR2- or CDR3-like regions of the D1 domain of CD4; (iv) that jacalin did not bind a recombinant soluble molecule containing the D1/D2 domains of CD4; and, (iv) that jacalin binding to CD4 is inhibited by sugars known to interact with the lectinic-site of jacalin. These data have implications for the understanding of the mechanism by which jacalin blocks HIV-1 infection of CD4+ cells. PMID- 8196668 TI - Serum amyloid A gene expression under acute-phase conditions involves participation of inducible C/EBP-beta and C/EBP-delta and their activation by phosphorylation. AB - Serum amyloid A (SAA) is a plasma protein whose synthesis is markedly increased in the liver during the inflammatory process. Previous analysis of SAA promoter function implicated the involvement of the CCAAT/enhancer-binding protein (C/EBP) in controlling this process. In this study, using antibodies against three C/EBP isoforms in DNA-binding and Western blot (immunoblot) assays, we found that in response to inflammatory signals, both C/EBP-delta and C/EBP-beta are induced and that their interactions with the SAA promoter element are necessary for the increased SAA gene expression. Cotransfections of liver cells with an SAA promoter-linked reporter chloramphenicol acetyltransferase gene and murine sarcoma virus-expressed C/EBP-delta or C/EBP-beta confirm such phenomena. The increased transactivating ability in the presence of the cellular phosphatase inhibitors okadaic acid and sodium orthovanadate, coupled with the observation that dephosphorylation severely inhibits the DNA-binding ability in vitro, implicates a role of phosphorylation in the regulation of the activities of the C/EBP-delta isoform. Consistent with these findings, we have detected higher levels of DNA-binding activity of C/EBP-delta prepared from cells treated with phosphatase inhibitors. We also present evidence that C/EBP-delta is a phosphoprotein. These results suggest that C/EBP-delta is regulated by phosphorylation and, in conjunction with C/EBP-beta, is one of the major proteins responsible for the increased transcription of the SAA gene in response to inflammatory stimuli. PMID- 8196670 TI - Monitoring the formation of soluble immune complexes composed of idiotype and anti-idiotype antibodies by electron microscopy. AB - We have previously used immunoelectron microscopy (IEM) to generate a three dimensional map of idiotypic (Id) and isotypic epitopes on the Fab arms of HGAC 39 (Roux et al., 1987, Proc. natn. Acad. Sci. U.S.A. 84, 4984-4988), a mouse IgG3 monoclonal antibody (Mab). In this report, we analyse the geometry of the various types of immune complexes formed by the interaction of HGAC 39 with Mab directed against four mapped epitopes. Moreover, by sampling of reaction mixtures over time, we show that the kinetics of each of the subpopulations of immune complexes, as defined by geometric configuration, can be determined. The data show that for each antibody (Ab)-HGAC 39 combination the rate of immune complex formation was greatest during the first 1.5-3.5 min but that additional complexes formed through the remainder of the half hour assay period. As anticipated, complexes composed of even number units predominated (primarily dimers and tetramers) and most of these were in the form of closed rings. The data also suggest that the location and orientation of the epitopes on HGAC 39 to which the monoclonal antibodies were bound has an influence on the types of immune complexes generated. Specifically we observed that those anti-idiotype Abs that bind to the distal tip of Fab arms (i.e. in the CDR) are less likely to produce bivalently associated ringed dimers than antibodies that bind to epitopes that are proximal to the CDR and that project laterally from the surface of the Fab arms. These data are interpreted in terms of restrictions on hinge mediated flexibility and steric inhibition between adjacent Fab arms on HGAC 39. PMID- 8196672 TI - Calcium ion binding regions in C-reactive protein: location and regulation of conformational changes. AB - C-reactive protein (CRP) is a pentameric acute phase serum protein composed of identical 206 amino acid subunits that associate by non-covalent bonds. The biological activities ascribed to CRP are initiated by binding ligands via the single PC-binding site within each subunit. CRP binding to PC requires a conformational change in the intact pentraxin triggered by the binding of two free Ca2+ ions per subunit. Residues 134-148 of each subunit were previously implicated by indirect measures as one of the Ca(2+)-binding sites. In this study, 45Ca2+ autoradiography revealed that fragments of CRP of 6.5 and 16 kDa generated by proteolysis between residues 146 and 147 bind Ca2+ indicating that a second Ca(2+)-binding site is located within the C-terminal 60 amino acids. Synthetic peptides corresponding to residues 134-148 and 152-176 both bound 45Ca2+ in equilibrium dialysis experiments with a Kd = 5.2 x 10(-4) and 1.7 x 10( 4) M, respectively. The addition of Ca2+ to peptide 152-176 induced a shift in the CD-spectra between 210 and 230 nm. Rabbit anti-peptide 152-176 antibody (Ab) inhibited the availability of an epitope within the PC-binding site of CRP recognized by mAb EA4-1. Reactivity of CRP with both anti-peptide 134-148 mAb and anti-peptide 152-176 Ab enhanced the expression of the PC-binding site epitope. The results suggest that the two distinct Ca(2+)-binding sites within each CRP subunit are composed of residues 134-148 and 152-176 and that these two nearly adjacent sites cooperate to exert an allosteric change in conformation allowing access to the PC-binding site. PMID- 8196673 TI - Evidence for mitochondrial dysfunction in Parkinson's disease--a critical appraisal. AB - There is now considerable evidence to support a defect of the mitochondrial respiratory chain, and complex I in particular, in Parkinson's Disease (PD). However, the site specificity of the defect within the chain, its anatomical selectivity within the brain, and its presence in other tissues still remain controversial. Much of the present confusion surrounding the mitochondrial defect can be dispelled by careful analysis of the available data. The molecular basis of the deficiency and its relevance to the pathogenesis of PD remain unknown. Nevertheless, the complex I deficiency in PD provides a direct biochemical link between the idiopathic disease and the MPTP toxin model. The relationship between the mitochondrial defect and other abnormalities within the PD substantia nigra suggests that a self amplifying cycle of events might be precipitated either by a genetic or environmentally induced abnormality of mitochondrial function or free radical metabolism. Alternatively, a biochemical event separate from these might precipitate a cascade which terminates in complex I dysfunction and free radical formation. An understanding of the molecular basis of the complex I defect in PD and its relationship to other biochemical changes will provide important insight into the potential chain of events that lead to dopaminergic cell death in PD. PMID- 8196671 TI - Lithocholic acid inhibits the expression of HLA class I genes in colon adenocarcinoma cells. Differential effect on HLA-A, -B and -C loci. AB - Loss of HLA antigen expression is considered to be one of the mechanisms whereby tumor cells escape immune surveillance. We recently observed reduced or lost expression of HLA antigens during human colon carcinogenesis. We studied the effect of bile acids (BAs), long implicated in the pathogenesis of colon cancer, on the expression of HLA class I antigens in human colon adenocarcinoma cells. Lithocholic acid (LCA) decreased by 42% the expression of HLA class I antigens on the surface of these cells. This dose-dependent reduction was specific for both the target genes and the chemical structure of LCA, and was not evident in cultured liver cells. None of the other BAs that were tested manifested this effect. LCA, and to a lesser extent deoxycholic acid (DCA), decreased steady state HLA class I mRNA levels. LCA decreased the rate of transcription of HLA-B (64%) and HLA-C (87%) but not HLA-A; DCA had a similar but less pronounced effect. In transient gene expression (CAT assays) experiments, we evaluated the role of a 0.6-0.7 kb EcoRI/XbaI sequence from the 5' flanking region of HLA-A2, B7 and -Cw7 genes in the regulation of class I gene expression by LCA. LCA down regulated by 70% the expression of the reporter gene for all three genes. We interpret these results as indicating a differential regulation of the three HLA loci by LCA. Our findings, demonstrating a profound effect of LCA on HLA class I gene regulation, raise the possibility that such a mechanism may be operative in vivo. PMID- 8196675 TI - Cerebellar ataxia, dystonia, and tremor within a family: variable phenotypes of a single genetic disorder? AB - We report a non-Jewish, Anglo-Saxon, American family, in which one sibling has dystonia, a second has cerebellar ataxia, and a third has a combination of dystonia and ataxia. All three siblings have pyramidal signs. Their mother and maternal uncle have tremor, and their maternal grandmother may have had a neurodegenerative disorder. Although the inheritance pattern is uncertain, this may represent phenotypic variability resulting from a single gene mutation. The multiple phenotypes within this family do not fit any known inherited neurodegenerative or metabolic disorder. PMID- 8196674 TI - The initiation of normal walking. AB - Lower extremity electromyograms (EMGs), ground reaction forces, and body motion were measured during the brisk initiation of forward walking performed by 12 healthy adults, aged 20 to 82 years. Gait was initiated 20 times in response to a visual cue. During gait initiation, the body rotated about the ankles like a flexible inverted pendulum. The muscles of the lower extremities were activated stereotypically so as to create moments of force about the ankles that propelled the body toward the stance foot and into forward motion. All volunteers exhibited similar patterns of gait initiation, which were so reproducible that computer averaging of multiple steps by each person was possible. Gait initiation is a stereotyped sequence of postural shifts that culminates in a forward step. Disturbances of gait initiation could result from abnormalities in postural control, movement, or their integration. PMID- 8196676 TI - "Minimal change" multiple system atrophy. AB - We describe the pathological findings in two patients who developed atypical parkinsonism and autonomic failure, leading to a diagnosis of multiple system atrophy (MSA). Postmortem examination of the brain showed cell loss restricted to substantia nigra and locus coeruleus. However, glial cytoplasmic inclusions (GCIs) were present in both cases. We propose that GCIs are highly suggestive of a pathological diagnosis of MSA in the absence of detectable cell loss outside pigmented brain stem nuclei and that brains from cases of atypical parkinsonism should routinely be examined for their presence. PMID- 8196677 TI - Chronic administration does not alter the accumulation of L-dopa into muscle. AB - Rats were treated for 12 months with L-dopa (191.4-210.4 mg/kg/day) plus carbidopa (23.9-26.2 mg/kg/day), or carbidopa (24.4-26.3 mg/kg/day) alone. Four days after drug withdrawal, animals received an acute challenge with either L dopa (50 mg/kg p.o.) alone or following acute carbidopa (25 mg/kg i.p.) pretreatment, and the uptake and metabolism of L-dopa in muscle was studied. Following the acute bolus challenge, plasma levels of L-dopa peaked between 0.5 and 3 h after L-dopa alone and between 1.5 and 2 h after L-dopa plus carbidopa. Peak levels in muscle were observed between 1.5 and 4 h after L-dopa administration, and this accumulation was enhanced by the acute pretreatment with carbidopa. Chronic administration of L-dopa plus carbidopa or carbidopa alone for 12 months had no effect on the accumulation of L-dopa into muscle following the acute challenge with L-dopa alone or after carbidopa pretreatment. 3-O Methyldopa, dopamine, DOPAC, and HVA levels were elevated in both plasma and muscle following acute oral challenge with L-dopa or L-dopa plus carbidopa. Levels of these metabolites were unaffected by chronic administration of L-dopa plus carbidopa or carbidopa alone. In conclusion, chronic administration of L dopa plus carbidopa did not alter the accumulation of L-dopa into muscle following an acute oral challenge with the drug, with or without carbidopa pretreatment. PMID- 8196678 TI - Severe evening dyskinesias in advanced Parkinson's disease: clinical description, relation to plasma levodopa, and treatment. AB - We report four patients with Parkinson's disease who had an unusual pattern of severe chorea and dystonia in the evenings only. The temporal pattern of abnormal movements and simultaneous monitoring of plasma levodopa and clinical state were consistent with dyskinesias associated with subtherapeutic (low dopa dyskinesias) rather than peak concentrations of levodopa (high dopa dyskinesias). In two patients, addition of a direct-acting dopamine receptor agonist was helpful in ameliorating this complication of antiparkinson therapy. PMID- 8196679 TI - Electromyographic silent period after transcranial brain stimulation in Huntington's disease. AB - The silent period evoked by transcranial (TCS) and nerve stimulation was studied in the hand muscles in 13 patients with Huntington's disease and in 11 normal subjects. The duration of the silent period after TCS was longer in patients and correlated significantly with the severity of chorea; in contrast, the duration of the silent period after nerve stimulation was similar in patients and controls. The prolongation of the cortical silent period suggests that the duration of the silent period is a functional correlate reflecting basal ganglia influence over the motor cortex. PMID- 8196680 TI - Exteroceptive reflexes in dystonia: a study of the recovery cycle of the R2 component of the blink reflex and of the exteroceptive suppression of the contracting sternocleidomastoid muscle in blepharospasm and torticollis. AB - The recovery cycle of the R2 component of the blink reflex and the exteroceptive suppression of EMG activity in the contracting sternocleidomastoid muscle produced by electrical stimulation of the supraorbital nerve were studied in normal subjects and in patients with either blepharospasm or torticollis. The latencies of the reflexes were normal, suggesting that the neural structures that mediated them were intact. However, the recovery of the R2 component of the blink reflex was enhanced in patients with either blepharospasm or torticollis. Also, the size of the exteroceptive suppression of the sternocleidomastoid muscle was reduced in both groups of patients. Our results are indicative of abnormalities of interneurons mediating exteroceptive reflexes in patients with craniocervical dystonia that are not restricted to the systems controlling the muscle involved in the dystonia. PMID- 8196681 TI - Withdrawal akathisia: case reports and a proposed classification of chronic akathisia. AB - Two patients with akathisia developing only after neuroleptic dosage reduction or withdrawal are described. The literature dealing with tardive or chronic akathisia is reviewed with an emphasis on the existence of variants including the occurrence of symptoms upon withdrawal of the causative drug. A classification of tardive or chronic akathisia syndrome is proposed. PMID- 8196682 TI - Gait abnormality in essential tremor. AB - Essential tremor (ET) has been described as a monosymptomatic disorder. In reports describing large series of patients with ET, there are rare patients who exhibit a noticeable gait disorder. However, we have observed that patients with ET and normal gait often exhibit an abnormality of tandem gait. To investigate this observation, we examined whether a gait disorder was present in 36 consecutive patients (mean age 69) with ET. We employed a tremor rating scale that scored tremor amplitude, location, and disability. In all patients, gait and tandem gait were separately evaluated. Eighteen of 36 patients (50%) exhibited tandem gait abnormalities in the presence of a normal narrow-based gait compared to 11 of 40 age-matched controls (28%) (p < 0.05). Abnormality of tandem gait was more frequently present in older ET patients and those with > 5 years of disease duration. No relationship was found between presence of tandem gait abnormality and gender, tremor severity, head involvement, or positive family history. The finding of a tandem gait abnormality in 50% of ET patients suggests that cerebellar dysfunction may be important in its pathophysiology. PMID- 8196683 TI - Symptomatic relief from treatment-induced psychosis in Parkinson's disease: an open-label pilot study with remoxipride. AB - Current treatment strategies for levodopa-induced psychosis in Parkinson's disease have had limited success. Remoxipride, a selective D2 receptor antagonist, was administered in an open label pilot study to seven parkinsonian patients exhibiting thought disorder. Symptoms improved significantly in six patients after treatment durations of 1-6 months and cleared completely in two individuals. One patient (at age 90 the oldest in the group) could not tolerate the compound due to significant motor deterioration, and the drug had to be discontinued after 1 week. In all remaining patients, no motor complications appeared, and therapeutic effects of remoxipride continued for up to 3 months after treatment cessation and have lasted for 2 years now in one individual. Further study of this compound in the context of treatment-induced psychosis in Parkinson's disease appears to be warranted. PMID- 8196684 TI - Novel rat cardiac arrest model of posthypoxic myoclonus. AB - We describe the time course of and pharmacology associated with auditory-induced muscle jerks following cardiac arrest in rats. The data indicate that several key features of this model mimic those of human posthypoxic myoclonus. Similar to the human form, the muscle jerks appear in the rats following an acute hypoxic episode (cardiac arrest). Initially, it is known that both spontaneous and auditory-induced myoclonus are present in these animals; some cardiac-arrested rats also exhibit seizures. Over the first few days after the arrest, episodes of both the seizure activity and spontaneous myoclonus disappear. The auditory induced myoclonus continues to worsen, reaches a peak about 2 weeks after the arrest, then declines over time to subnormal levels. The auditory-induced muscle jerks exhibited by the cardiac arrested animals are attenuated by the typical antimyoclonic drugs 5-hydroxytryptophan, valproic acid, and clonazepam. In addition, the novel anticonvulsant felbamate was found to have antimyoclonic properties. The data suggest that this rat cardiac arrest model may be a valuable tool for investigating the pathophysiologic mechanisms of posthypoxic myoclonus and for developing new therapeutic strategies for treating the disorder. PMID- 8196685 TI - Smoking and Parkinson's disease. AB - Smoking was examined in relation to Parkinson's disease (PD) in a population based study in northern Manhattan (New York City) because of its putative "protective effect." Using a case-control design, information on smoking and associated behaviors was obtained in structured interviews after standard diagnostic evaluations in both cases and controls. The overall prevalence of smoking in the population was 43.7%, decreasing to 37% after age 85. Smoking was most frequent in men, Blacks, and in both cases and controls using alcohol once per week or more. Cases had quit smoking more often than controls (87 vs. 64%), and had smoked for significantly fewer years (31 vs. 41 yrs; p < 0.05 for both). The age-at-onset for smokers with PD was similar to age-at-onset for nonsmokers with PD. The odds ratio (OR) for a history of smoking associated with PD was 1.1 (95% CI 0.7-1.8). No protective gradient was associated with heavier smoking patterns. However, the odds that patients with PD were still smoking at the time of the interview were significantly less than those for controls (OR = 0.2; 95% CI 0.1-0.5). These results do not support the hypothesis that smoking protects against PD; rather they strongly imply the converse, that PD reduces smoking. PMID- 8196686 TI - Development of resistance to botulinum toxin type A in patients with torticollis. AB - Between 1984 and 1992, 559 patients with torticollis were treated with botulinum toxin type A (btx) injections. Twenty-four of these 559 patients (4.3%) had serological evidence of antibodies to btx by mouse neutralization assay. Some of the 559 patients had only one or two injection series, whereas others were lost to follow-up, so that the actual prevalence of serologically detectable antibodies may be higher than 4%. In addition, some patients who improved after btx injections lost benefit and stopped developing muscle atrophy from adequate doses of btx, without serological evidence of antibodies. To evaluate the risk factors for btx resistance (loss of benefit and muscle atrophy after injections with or without serological evidence of antibodies), we reviewed the records of a cohort of torticollis patients injected over 2-45 months (mean, 23 months) beginning in 1988. Eight of 76 patients (10.5%) developed btx resistance. Compared to nonresistant patients from the same cohort, these eight patients received more frequent injections, had more "booster injections" 2-3 weeks after an initial injection, and received higher doses of btx per treatment. In order to minimize the risk of developing btx resistance, therefore, we recommend that physicians wait as long as possible (at least 1 month) between btx injections, avoid booster injections, and use the smallest possible doses. PMID- 8196687 TI - Motor program memory storage in Parkinson's disease patients tested with a delayed response task. AB - We used a delayed response paradigm to test the hypothesis that the prolonged reaction time in patients with Parkinson's disease (PD) is related to a deficiency in their ability to store a motor program in memory while waiting to move. PD patients, both on and off medication, were compared with age-matched normal subjects during arm movements directed toward a target light. The target light was displayed either during a 3- to 9-s delay or for only 1 s followed by a 2- to 8-s delay before the go signal. At the end of the delay, subjects were required to begin movement rapidly. The reaction time of PD patients was longer than normal and increased slightly when the patients were off medication. The patients had no excessive increase in reaction time with delay in either task compared with the control subjects. We conclude that patients with PD can hold a motor program in memory storage for at least 8 s. PMID- 8196688 TI - Facial action myoclonus in patients with olivopontocerebellar atrophy. AB - We studied four patients with familial olivopontocerebellar atrophy (OPCA) who had abnormal twitching of the cheeks and perioral muscles induced by facial movements. With the muscles at rest, electromyographic (EMG) recordings of the orbicularis oris and risorius muscles revealed myokymic discharges in the absence of visible movements. With voluntary contraction, the EMG showed synchronous discharges in the orbicularis oris and risorius muscles ipsilaterally associated with visible twitching. The duration of the EMG bursts was 10 to 75 ms with a frequency of 8 to 25 Hz, which suggested that the abnormal twitching was most consistent with a myoclonic disorder. Because it was induced by activation of the facial muscles, this movement disorder represents a form of action myoclonus. PMID- 8196693 TI - Continuous involuntary auricular movements associated with an anterior parietal tumor. PMID- 8196692 TI - Bilateral hemifacial spasm. PMID- 8196691 TI - Effectiveness of botulinum toxin type A against painful limb myoclonus of spinal cord origin. AB - Botulinum toxin is now an established treatment for blepharospasm, hemifacial spasm, spasmodic torticollis, and spastic dysphonia. We report the effectiveness of botulinum toxin against painful limb myoclonus of spinal cord origin. The patient, a 16-year-old girl with a pulmonary vascular anomaly, Scimitar syndrome, suffered from an acute spinal cord infarct at age 11. She was left with paralysis of the right leg and bladder dysfunction. Four years after the original insult, she developed "painful cramping" and involuntary movements of the left thigh, which were unresponsive to a wide range of therapeutic trials. The movements were continuous, rhythmic, and confined to the left quadriceps muscles. Electromyographic examination revealed continuous myoclonic discharges. Treatment with botulinum toxin in the left quadriceps muscles resulted in complete cessation of pain and marked reduction in amplitude of the movements, both clinically and electromyographically. This observation indicates the efficacy of botulinum toxin in the treatment of painful spinal myoclonus. PMID- 8196690 TI - Limb dystonia following electrical injury. AB - Electrical injuries of the extremities may cause paralysis, muscle atrophy, sensory deficit, causalgia, and reflex sympathetic dystrophy (RSD). Limb dystonia has rarely been reported following electrical injury to an extremity, although it may result from cerebral hemisphere electrical trauma. Following electrical injury to the upper extremity, three patients developed limb dystonia accompanied by severe pain and sensory symptoms in two patients and features of RSD in one patient. Two patients received botulinum toxin injections without functional benefit. The mechanism of dystonia following peripheral trauma is unknown but may relate to reorganization of central synaptic connections, possibly in the spinal cord. PMID- 8196694 TI - Delayed onset of "rubral tremor" 23 years after brainstem trauma. PMID- 8196689 TI - Infantile hypotonia and paroxysmal dystonia: a variant of alternating hemiplegia of childhood? AB - We report 2 children with early onset of hypotonia and frequent episodes of paroxysmal dystonia. The episodes were abolished even by brief naps. One of the children developed alternating hemiplegia in the second decade. These children seem to have a variant of the now well-recognized syndrome of alternating hemiplegia of childhood. In that disorder, episodes of alternating hemiplegia develop before the age of 18 months. This syndrome must be considered in the differential diagnosis of paroxysmal dystonia in childhood. PMID- 8196695 TI - N-methyl-D-aspartate (NMDA) antagonist and Parkinson's disease: a pilot study with dextromethorphan. PMID- 8196697 TI - Movement disorders with cerebral toxoplasmosis and AIDS. PMID- 8196696 TI - Salbutamol and moaning. PMID- 8196698 TI - AAEM minimonograph #43: neuromuscular problems in the performing arts. AB - Over the past 10-15 years, there has been increasing interest in the health problems of performing artists. In this review, I will discuss the major playing related disorders seen in instrumental musicians. Among the 672 instrumentalists evaluated, the major diagnoses identified included musculoskeletal disorders in 64%, peripheral nerve problems in 22.5%, and focal dystonia in 7%. Sixty percent of instrumentalists were female although males predominate in the group with focal dystonia. The average age of those evaluated was 32 years. Among musculoskeletal disorders overuse syndrome is the most common. Frequent peripheral nerve disorders include thoracic outlet syndrome, carpal tunnel syndrome, and ulnar neuropathy. A characteristic distribution of symptoms and signs is identified for each instrument group. Electrodiagnostic studies are an important part of the evaluation of these disorders. With carefully designed treatment, the majority of instrumental musicians can be returned to full and pain-free playing activities. The success rate is highest in some entrapment neuropathies but remains low in focal dystonia. PMID- 8196699 TI - Osteomalacic myopathy. AB - A 45-year-old woman reported the development of thigh pain followed within a year by proximal muscle weakness. Clinical findings included short stature, prominent kyphoscoliosis, proximal weakness, and brisk reflexes. Recognition of an increased level of serum alkaline phosphatase and hypophosphatemia led to the diagnosis of osteomalacia. Identification of iron deficiency anemia and hypocholesterolemia implicated previously unrecognized gluten-sensitive enteropathy with associated vitamin D malabsorption as the cause of the osteomalacia. Adherence to a gluten-free diet and treatment with vitamin D2 resulted in weight gain, resolution of pain, and improvement in strength within 3 months. Painful proximal weakness and hyperreflexia may be the initial and primary manifestations of osteomalacia, a readily treatable cause of muscle and bone disease. PMID- 8196700 TI - Association between muscle architecture and quadriceps femoris H-reflex. AB - The purpose of the present study was to establish the relationship between muscle architecture and H-reflex recordings in quadriceps femoris muscle. H-reflexes were elicited in human quadriceps femoris muscle over a broad area of skin to document the shape and amplitude of the H-potentials. This, in combination with recording monopolar and bipolar H-potentials, was performed to determine the location and method for measuring maximum-amplitude H-reflexes. The influence of neural and peripheral factors on the H-potential during passive length changes was studied by comparing the amplitude of H-potentials to motor unit action potentials. Monopolar recordings of the H-potential were found to be preferable to bipolar recordings because of the reproducibility of shape and easier distinction between the M- and H-potentials. The location for recording maximum H potentials was in the distal one third of the quadriceps femoris muscle, over the border between vastus lateralis and rectus femoris. The inferred relationship between H-potential amplitude and reflex excitability must be made with caution in quadriceps femoris muscle because the amplitude of both the motor unit potential and H-potential change as a function of muscle length. PMID- 8196701 TI - Sodium channels accumulate at the tips of injured axons. AB - The axolemmal distribution of voltage-gated sodium channels largely determines the regions of axonal electrical excitability. Using a well-characterized anti sodium channel antibody, we examined peripheral nerve fibers focally injured by exposure to the neurotoxic agent, potassium tellurite (K2TeO3). Immunocytochemical and radioimmunoassay data showed a focal accumulation of sodium channels within the tips of injured axons. The major increase in sodium channel concentration occurred between 7 and 11 days after toxin exposure; however, immunocytochemically, excess sodium channels persisted in several axonal endings for a much longer time. The accumulation of sodium channels at injured axonal tips may be responsible, in part, for ectopic axonal excitability and the resulting abnormal sensory phenomena (especially pain and paresthesias) which frequently complicate peripheral nerve injury in humans. PMID- 8196703 TI - Satellite cell activity is required for hypertrophy of overloaded adult rat muscle. AB - Hypertrophy of extensor digitorum longus muscle, overloaded by the removal of the synergist tibialis anterior (TA) muscle, in growing rats is inhibited if endogenous satellite cells are sterilized by exposure to irradiation. However, normal muscle growth is not eliminated, only diminished. To test whether irradiated, overloaded muscle can hypertrophy in the absence of normal growth related stimuli, experiments were conducted on mature rats. TA muscle ablation caused hypertrophy of EDL muscle, characterized by a significant increase in muscle mass and the size of type IIx and type IIb fibers, and a proportional increase in the number of myonuclei. When ablation was preceded by irradiation, hypertrophy did not occur. The results indicate that satellite cell activation, division, and fusion is necessary for compensatory hypertrophy of fully mature muscle, and may be important to the understanding of the limits of recovery of inherited muscle myopathies treated by myogenic cell implantation. PMID- 8196702 TI - Pseudofacilitation: a misleading term. AB - The possible causes of the transient enlargement of muscle compound action potentials during repetitive stimulation ("pseudofacilitation") are considered. The phenomenon cannot be due to mechanical artefact, while hypersynchronization of the muscle fiber action potentials, the usual explanation, can only make a minor contribution. A more convincing explanation, for which there is now experimental evidence, is that the muscle fibers undergo hyperpolarization, due to the intramuscular release of norepinephrine and consequent stimulation of the electrogenic Na+,K(+)-pump. Defective phosphorylation of the Na+,K(+)-pump is a possible cause of the transient weakness and myotonia in myotonic dystrophy. PMID- 8196705 TI - Elimination of superfluous neuromuscular junctions in rat calf muscles recovering from botulinum toxin-induced paralysis. AB - In order to determine the fate of the superfluous neuromuscular junctions (NMJs) formed during the course of botulinum toxin (BoTx)-induced paralysis, we have quantified the change in the total length of the nerve muscle contact area(s) following BoTx injection into rat calf muscles. The results indicate that: (1) at least some of the superfluous NMJs are eliminated following muscle recovery; (2) synapse elimination is a slow process, as 4 months after recovery it was not yet complete; (3) muscles with different content of type I and II fibers follow a different time course during synapse formation and elimination. We further investigated the possibility that the neural cell adhesion molecule (NCAM) would be the element whose loss from the NMJ might play a role in synapse elimination. Using immunofluorescence and immunoelectron microscopy we show that NCAM is exclusively localized between nerve terminals and Schwann cells and not between nerve terminals and muscle. This localization was maintained throughout paralysis and following recovery, suggesting that NCAM does not play a role in synapse elimination. PMID- 8196704 TI - Deficits in the function of small and large afferent fibers in confirmed cases of carpal tunnel syndrome. AB - Nerve conduction studies and measurements of thermal thresholds (hot and cold) were performed in 25 healthy control subjects and 24 patients with carpal tunnel syndrome: first, to compare the extent of abnormality demonstrable in the function of large and small afferent axons; second, to correlate these abnormalities with clinical severity; and third, to validate a modified form of palmar stimulation as an additional neurophysiological test in suspected carpal tunnel syndrome. The routine nerve conduction studies compared the amplitudes and conduction velocities from digit II and digit V to wrist and for the digit-II potential between wrist and elbow. With palmar stimulation, the palm-to-wrist segment was compared to the simultaneously evoked antidromic digital potential (palm-to-index). Thermal threshold testing involved determination of hot and cold thresholds for digit II and digit V using an automated forced-choice procedure. In the patients there was selective slowing of conduction across the palm-to wrist segment with normal velocities distally and proximally, and there was clear evidence of abnormal small-fiber function, with higher thresholds for both hot and cold sensation. However, the thermal abnormalities also involved the ulnar territory, equally so for cold threshold but significantly less so for hot threshold. Thermal threshold testing confirmed the clinical impression that small fiber dysfunction is important in carpal tunnel syndrome, but the abnormal findings for the ulnar-innervated digit V suggest that this test will not be routinely useful for the early detection of compression or entrapment neuropathies. PMID- 8196707 TI - Suppression and long latency excitation of single spinal motoneurons by transcranial magnetic stimulation in health, multiple sclerosis, and stroke. AB - Whether or not suppression at the level of the spinal motoneuron plays a role in motor deficits such as central paresis is unknown. In this study suppression in the firing of tonically active low threshold single motoneurons following low intensity transcranial magnetic stimulation is described in health and disease. Changes in firing probability in the absence of an early excitatory response were studied in a total of 14 motor units from 4 healthy subjects, 5 patients with multiple sclerosis, and 1 patient with stroke. Firing probability began to fall 18-59 ms after the stimulus and remained low for a period of 27-133 ms. There were no obvious differences between the three subject groups. The change in firing probability was not associated with specific physical signs. Late rises in firing probability were seen in 7 of the 14 motor units at latencies that were similar to the secondary peak which is known to occur with higher stimulus intensities. It is argued that the mechanism of partial suppression is not dependent on the full integrity of the pyramidal tract and is likely to involve a transient withdrawal of descending excitatory drive rather than an inhibitory postsynaptic potential at the spinal motoneuron. PMID- 8196706 TI - The relationship between body mass index and the diagnosis of carpal tunnel syndrome. AB - Increased weight and, more recently, body mass index (BMI), have been suggested as risk factors for carpal tunnel syndrome (CTS). In an effort to determine the relative risk (RR) of obesity in the development of CTS, 949 patients who had an evaluation of the right upper extremity that included motor and sensory conduction studies of the median and ulnar nerves were reviewed. Of these patients, 261 were diagnosed with a median mononeuropathy at the wrist. Those individuals who were classified as obese (BMI > 29) were 2.5 times more likely than slender individuals (BMI < 20) to be diagnosed with CTS. Forty-three percent of obese women and 32% of obese men had the diagnosis of CTS compared to 21% of slender women and 0% of slender men. PMID- 8196709 TI - Voluntary contraction and responses to submaximal cervical nerve root stimulation. AB - Voluntary contraction of hand muscles increases compound muscle action potential (CMAP) amplitudes evoked by submaximal electrical percutaneous cervical stimulation (EPCS). This has been reported to be due to an intraspinal, presynaptic mechanism. We studied the effects of voluntary contraction on hypothenar CMAP amplitudes in 5 volunteers following electrical peripheral nerve stimulation at the wrist, EPCS, magnetic stimulation at the neck and the effects of a conditioning subthreshold cortical magnetic stimulus on CMAPs evoked by EPCS at rest. CMAP amplitudes increased with voluntary contraction of the target muscle, regardless of type or location of stimulus (P < 0.001). No increase in CMAP amplitude occurred when a conditioning transcranial stimulus was employed with EPCS (P = 0.35). Our findings indicate a peripheral rather than central mechanism underlies this effect of voluntary contraction. It is probably related to the recruitment order of motor axons, comparing voluntary activation with electrical or magnetic stimulation. PMID- 8196708 TI - Immunocytochemistry of muscle cytoskeletal proteins in acid maltase deficiency. AB - Immunocytochemistry of dystrophin, spectrin, vinculin (sarcolemma-specific proteins), and desmin (an intermediate filament protein) were investigated in 5 patients with acid maltase deficiency (AMD). One patient had infant onset, 2 had childhood onset, and 2 had adult onset. All had a vacuolar myopathy with autophagic vacuoles containing glycogen and cytoplasmic degradation products. Dystrophin, spectrin, and vinculin were localized at the sarcolemma as in normal muscle fibers. Within the cytoplasm of many fibers, immunoreactivity for the three proteins was seen as single or multiple spots or as circular structures, which most likely corresponded to the limiting membrane of vacuoles. Desmin was overexpressed at the periphery of some vacuoles. It is plausible that, before exocytosis occurs, sarcolemma-specific proteins appear within the vacuole membrane. Vacuole immunolabeling frequently occurred in the patients with childhood and adult onset AMD, but very rarely occurred in the case with infant onset. We hypothesize that a reduced exocytosis rate might explain the infrequent vacuole immunolabeling and the early onset of the infant form of the disease. PMID- 8196710 TI - Ophthalmoplegia, demyelinating neuropathy, leukoencephalopathy, myopathy, and gastrointestinal dysfunction with multiple deletions of mitochondrial DNA: a mitochondrial multisystem disorder in search of a name. AB - This article describes a 37-year-old woman with progressive external ophthalmoplegia, peripheral neuropathy, and chronic intractable diarrhea. Laboratory studies disclosed lactic acidosis, ragged red fibers lacking cytochrome c oxidase, high-normal muscular mitochondrial enzymes, demyelinating neuropathy, leukoencephalopathy and multiple mitochondrial DNA deletions. This is the fourth patient described with this clinical syndrome, which represents a separate entity among multisystemic mitochondrial disorders. The patient described here is the first with this syndrome to have multiple mitochondrial DNA deletions. PMID- 8196712 TI - Axonal Guillain-Barre syndrome. AB - The issue of "axonal" Guillain-Barre syndrome (GBS) remains controversial. Supportive evidence comes from pathological examination of peripheral nerves in 4 extreme cases of GBS 17-29 days after onset which showed severe axonal degeneration without inflammatory-demyelination. It has been suggested that inflammatory-demyelination may have been missed. This is difficult to disprove but it seems unlikely, given the known correlation between the severity of axonal degeneration and inflammation/demyelination in the experimental model of GBS, experimental allergic neuritis (EAN). Electrically inexcitable nerves in GBS may reflect axonal degeneration, terminal demyelination or both. This finding proved to be a sign of poor prognosis in 19 of 27 (70%) patients, although a good outcome occurred in some cases. PMID- 8196713 TI - Pathogenesis of axonal Guillain-Barre syndrome: hypothesis. AB - Pathologic studies of acute motor axonal neuropathy show strong evidence of the presence of primary axonal Guillain-Barre syndrome (GBS). The pathogenesis of axonal GBS is speculated to be as follows: (1) Infection by an organism induces the high production of a cross-reactive antibody between an infectious agent and the motor nerve axon in patients with a particular immunogenetic background. (2) The antineural antibody binds to the motor nerve terminals, thereby inhibiting motoneuron excitability and causing muscular weakness. (3) Binding of the antineural antibody, or subsequent functional impairment of the motoneurons, causes the motor axon to degenerate from the terminals. (4) In severe cases, extensive axonal loss and central chromatolysis of the motoneurons occur. These inhibit recovery and lead to a poor functional prognosis. PMID- 8196716 TI - Proximal weakness as the primary manifestation of myotonic dystrophy in older adults. PMID- 8196714 TI - Aseptic meningitis as a complication of intravenous immunoglobulin therapy for myasthenia gravis. PMID- 8196711 TI - There are no neurophysiologic features characteristic of "axonal" Guillain-Barre syndrome. AB - Classical views hold Guillain-Barre syndrome (GBS) as a primary inflammatory demyelinating neuropathy in which secondary axonal degeneration may occur, particularly when inflammatory lesions are severe. Feasby and colleagues proposed that primary axonal degeneration can also cause GBS characterized by inexcitable motor nerves and poor outcome. This hypothesis rests largely on the results of a single autopsy in which no inflammation or demyelination were found. Using an illustrative case report confirming earlier studies, we point out that inexcitable motor nerves (or low amplitude compound muscle action potentials [CMAPs]) are of ambiguous significance and may reflect distal demyelination, causing conduction block between distal stimulation sites and target muscles, a pattern not uncommon in GBS. Recovery from such lesions may occur within weeks with restoration of CMAP amplitudes. The recognition of a yet unproven axonal variant of GBS cannot be based solely on documentation of inexcitable motor nerves in the context of rapidly developing weakness. PMID- 8196717 TI - Delayed diagnosis of Lambert-Eaton myasthenic syndrome in a patient presenting with recurrent refractory respiratory failure. PMID- 8196715 TI - Comparison of magnetic coil and needle-electrical stimulation in diagnosis of lumbosacral radiculopathy. PMID- 8196718 TI - Standardization of a modified surface-EMG method. PMID- 8196721 TI - Variations of perineurial thickness in peripheral neuropathies. PMID- 8196720 TI - Paraneoplastic myotonia. PMID- 8196722 TI - Human models provide pathophysiological information about single motor axonal regeneration. PMID- 8196719 TI - Myopathy of endogenous Cushing's syndrome: a review of the clinical and electromyographic features in 8 patients. PMID- 8196725 TI - Limitations of receiver operating characteristic curve analysis in the prediction of carpal tunnel syndrome (a reply) PMID- 8196724 TI - Limitations of receiver operating characteristic curve analysis in the prediction of carpal tunnel syndrome. PMID- 8196723 TI - Mixed axonal-demyelinating polyneuropathy as predominant manifestation of myotonic dystrophy. PMID- 8196726 TI - Cyclosporine in severe ulcerative colitis refractory to steroid therapy. AB - BACKGROUND: There has been no new effective drug therapy for patients with severe ulcerative colitis since corticosteroids were introduced almost 40 years ago. In an uncontrolled study, 80 percent of 32 patients with active ulcerative colitis refractory to corticosteroid therapy had a response to cyclosporine therapy. METHODS: We conducted a randomized, double-blind, controlled trial in which cyclosporine (4 mg per kilogram of body weight per day) or placebo was administered by continuous intravenous infusion to 20 patients with severe ulcerative colitis whose condition had not improved after at least 7 days of intravenous corticosteroid therapy. A response to therapy was defined as an improvement in a numerical symptom score (0 indicated no symptoms, and 21 severe symptoms) leading to discharge from the hospital and treatment with oral medications. Failure to respond to therapy resulted in colectomy, but some patients in the placebo group who had no response and no urgent need for surgery were subsequently treated with cyclosporine. RESULTS: Nine of 11 patients (82 percent) treated with cyclosporine had a response within a mean of seven days, as compared with 0 of 9 patients who received placebo (P < 0.001). The mean clinical activity score fell from 13 to 6 in the cyclosporine group, as compared with a decrease from 14 to 13 in the placebo group. All five patients in the placebo group who later received cyclosporine therapy had a response. CONCLUSIONS: Intravenous cyclosporine therapy is rapidly effective for patients with severe corticosteroid-resistant ulcerative colitis. PMID- 8196727 TI - Low-dose cyclosporine for the treatment of Crohn's disease. The Canadian Crohn's Relapse Prevention Trial Investigators. AB - BACKGROUND: Long-term corticosteroid therapy for Crohn's disease is associated with important types of morbidity, such as osteoporosis. Safe and effective alternative treatments are required. Although a short-term benefit of cyclosporine in active Crohn's disease has been suggested, the long-term safety and efficacy of this treatment have not been established. METHODS: We conducted a randomized, double-blind, placebo-controlled evaluation of the effect of 18 months of low-dose cyclosporine treatment on the course of Crohn's disease. Adult patients whose disease had been active within the previous two years were randomly assigned to receive cyclosporine (151 patients) or placebo (154 patients) in addition to their usual therapy. Randomization was stratified according to center and score on the Crohn's Disease Activity Index (193 patients had scores of 150 or less, and 112 had scores greater than 150). The primary outcome measure was clinically important worsening of Crohn's disease, defined as a 100-point increase in the Crohn's Disease Activity Index from the patient's base-line value. Secondary outcomes were the use of prednisone and 5-amino salicylates, mean score on the Crohn's Disease Activity Index and mean quality-of life score, and the need for surgery. RESULTS: The condition of more patients worsened with cyclosporine than with placebo (91 of 151, or 60.3 percent, vs. 80 of 154, or 51.9 percent; P = 0.10). The median time to worsening of disease in patients receiving cyclosporine was 338 days, as compared with 492 days in patients receiving placebo (P = 0.25; relative risk, 1.22; 95 percent confidence interval, 0.86 to 1.72). Analyses of the mean Crohn's Disease Activity Index and quality-of-life scores and of the use of prednisone and 5-aminosalicylates also failed to demonstrate benefit. CONCLUSIONS: In our patient population, the addition of low-dose cyclosporine to conventional treatment for Crohn's disease did not improve symptoms or reduce requirements for other forms of therapy. PMID- 8196730 TI - Images in clinical medicine. Extraintestinal manifestations of Crohn's disease. PMID- 8196728 TI - Diuretic therapy for hypertension and the risk of primary cardiac arrest. AB - BACKGROUND: The results of trials of the primary prevention of coronary heart disease have suggested that treating hypertension with high doses of thiazide diuretic drugs might increase the risk of sudden death from cardiac causes. In contrast, treatment with low doses of thiazide reduces the risk of coronary heart disease. METHODS: To examine the association between thiazide treatment for hypertension and the occurrence of primary cardiac arrest, we conducted a population-based case-control study among enrollees of a health maintenance organization. The case patients were 114 persons with hypertension who had a primary cardiac arrest from 1977 through 1990. The control patients were a stratified random sample of 535 persons with hypertension. The patients' treatment was assessed with the use of a computerized pharmacy data base. Records of their ambulatory care were reviewed to determine other clinical characteristics. RESULTS: The risk of primary cardiac arrest among patients receiving combined thiazide and potassium-sparing diuretic therapy was lower than that among patients treated with a thiazide without potassium-sparing therapy (odds ratio, 0.3; 95 percent confidence interval, 0.1 to 0.7). As compared with low-dose thiazide therapy (25 mg daily), moderate-dose therapy (50 mg daily) was associated with a moderate increase in risk (odds ratio, 1.7; 95 percent confidence interval, 0.7 to 4.5), and high-dose therapy (100 mg daily) was associated with a larger increase in risk (odds ratio, 3.6; 95 percent confidence interval, 1.2 to 10.8) (P value for trend, 0.02). The addition of a potassium sparing drug to low-dose thiazide therapy was associated with a reduced risk of cardiac arrest (odds ratio, 0.4; 95 percent confidence interval, 0.1 to 1.5). CONCLUSIONS: Both the dose of thiazide drugs and the addition of potassium sparing drugs influence the risk of primary cardiac arrest. These results may explain the differences in the effect of antihypertensive therapy on mortality from coronary heart disease in previous clinical trials. PMID- 8196731 TI - Images in clinical medicine. Uric acid stones in Crohn's disease. PMID- 8196729 TI - A decision analysis of streptokinase plus heparin as compared with heparin alone for deep-vein thrombosis. AB - BACKGROUND: It is uncertain whether patients with proximal deep-vein thrombosis should be treated with streptokinase followed by intravenous heparin or with intravenous heparin alone. Published reports indicate that streptokinase plus heparin increases the risk of bleeding, including central nervous system bleeding and death, but decreases the risk of postphlebitic syndrome. Previous recommendations regarding these treatments have not considered patients' preferences or the values they attach to the possible outcomes of therapy. METHODS: We used decision analysis to combine published estimates of the probabilities of various adverse outcomes of treatment (bleeding, pulmonary embolism, postphlebitic syndrome, and death) with the values patients placed on these outcomes. We questioned 36 patients about the values they attached to each outcome. Sixteen patients had had deep-vein thrombosis, and 20 had not. RESULTS: By the values they attached to the outcomes, all 36 patients indicated that they were unwilling to accept an increased risk of death to avoid postphlebitic syndrome. According to the decision analysis, heparin alone was the better treatment for all 36 patients. As compared with streptokinase plus heparin, heparin alone provided 29 days of additional life expectancy over the predicted life expectancy of 20 years. Although the difference between the two treatments was small, heparin alone remained the better treatment in sensitivity analyses that examined the reasonable ranges of probabilities of the clinical outcomes. CONCLUSIONS: The values patients placed on the outcomes of treatment for deep vein thrombosis support the use of heparin alone over the combined use of streptokinase and heparin. PMID- 8196733 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 26-1994. A 20-year-old Philippine woman with a soft-tissue mass in the forearm. PMID- 8196732 TI - Systemic lupus erythematosus. PMID- 8196736 TI - Diuretic therapy, hypertension, and cardiac arrest. PMID- 8196734 TI - Incorporating patients' preferences into medical decisions. PMID- 8196735 TI - Cyclosporine therapy for inflammatory bowel disease. PMID- 8196738 TI - Sugar and children's behavior. PMID- 8196737 TI - Sugar and children's behavior. PMID- 8196742 TI - Thrombolytic therapy for thrombosis of an aortic bioprosthetic valve. PMID- 8196744 TI - Health-related claims at fast-food chains. PMID- 8196739 TI - Sugar and children's behavior. PMID- 8196743 TI - Acetaminophen treatment nomogram. PMID- 8196740 TI - Sugar and children's behavior. PMID- 8196741 TI - More on Lorenzo's oil. PMID- 8196745 TI - Rapeseed meal-glucosinolates and their antinutritional effects. Part 3. Animal growth and performance. AB - On the basis of literature data biological properties of rapeseed glucosinolates, and especially their influence on the growth and weight of animals were characterized. The aim was to determine a limiting value of these compounds in diets for particular animal species and age groups at which no limitation of growth or development was observed. PMID- 8196746 TI - Rapeseed meal-glucosinolates and their antinutritional effects. Part 4. Goitrogenicity and internal organs abnormalities in animals. AB - This paper surveys the literature concerning biological properties of rapeseed glucosinolates, chiefly the goitrogenic activity of these compounds and their influence on the morphological and histological abnormalities of internal organs in animals. An attempt has been made to establish threshold glucosinolate levels in diet which trigger the onset or increase of internal organs impairment in animals depending on their species and breeding. PMID- 8196747 TI - Iron status in a population of Spanish schoolchildren. AB - Iron status was assessed in a population of 196 schoolchildren and adolescents divided into three age groups: 6-7 years (n = 60), 10-12 years (n = 63) and 13-15 years (n = 73). All subjects were from the Velez-Malaga area (province of Malaga) in southern Spain. Nutrient intakes and biochemical parameters related with iron status (number of red cells, hematocrit, hemoglobin, serum iron concentration, total iron-binding capacity and transferrin saturation) were measured. The results showed a lack of correlation between the nutrient intake and biochemical findings. Food intake calculations suggested that adolescent girls between 13 and 15 years of age were at greatest risk for iron deficiency (intakes covered only 71.6% and 84% of the iron and folic acid RDAs, respectively), followed by 10-12 year old girls and 6-7 year old boys. However, groups in which iron deficiency was most frequent according to the biochemical data were 6-7 year old boys (10%), followed by 13-15 year old adolescent boys (2.9%). PMID- 8196748 TI - Availability of calcium from kilkeerai (Amaranthus tricolor) and drumstick (Moringa oleifera) greens in weanling rats. AB - The present study was undertaken to determine the extent of calcium absorption in weanling rats from two types of greens rich in oxalates. The edible portions of greens namely kilkeerai (Amaranthus tricolor) and drumstick (Moringa oleifera) were analysed for moisture, calcium and total and soluble oxalates. Three groups of 6 male weanling albino rats were fed ad libitum on milk diet and two experimental diets containing greens. Urine and faecal samples were collected for a period of 7 days after 5 days of acclimatization period and were analysed for calcium. From the values obtained percent absorption and retention of calcium were calculated. Results revealed that calcium absorption and retention from milk diet (92 and 78%, respectively) were significantly higher than greens. Average calcium absorption and retention from greens diet were 75.5 and 60%, respectively. Presence of oxalates inhibited intestinal absorption of calcium. PMID- 8196750 TI - Influence of phospholipids on the lipoprotein lipase activity of heart membranes- in vitro experiments. PMID- 8196749 TI - Mould contamination and the influence of water activity and temperature on mycotoxin production by two aspergilli in melon seed. AB - Both the moisture levels and the incidence of mould contamination recorded for shelled water melon seed samples (22) obtained from 9 markets were generally higher as those recorded for the unshelled seed samples. 16 fungi, mostly toxigenic, were isolated from the surface-disinfected mouldy seeds. Of these isolates, 7, 3 and 2 species belonged to Aspergillus, Penicillum and Fusarium genera, respectively, while Botryodiplodia, Rhizopus, Sclerotium and Syncephalastrum had one representative each. Production of aflatoxins (B1, B2) by 5 toxigenic strains of Aspergillus flavus and of ochratoxin A by 4 toxigenic strains of A. ochraceus in melon seed at varying water activity (aw) and temperature levels were investigated. Of the aw levels (0.65, 0.70, 0.80, 0.90 and 0.98) provided, toxins were detected only at and above 0.80 with the peak production recorded at either 0.90 or 0.98 aw level. Whereas aflatoxins were produced and detected under all the test temperatures (15, 20, 25, 30, 35, and 40 degrees C), the elaboration of ochratoxin A was detected only as from 25 to 40 degrees C. Optimum temperature for toxin production by all the strains of the two fungi used was 30 degrees C. PMID- 8196752 TI - Clinton administration urges basic research boost in new budget plans. PMID- 8196751 TI - Resurgent infections. PMID- 8196753 TI - UK nuclear company funds broad study of genetic data. PMID- 8196754 TI - UK gene-release suspended after protests. PMID- 8196755 TI - DNA profiling on trial. PMID- 8196756 TI - DNA profiling on trial. PMID- 8196757 TI - DNA profiling on trial. PMID- 8196758 TI - Optimism abounds. PMID- 8196759 TI - Saving the tiger in the wild. PMID- 8196760 TI - Vatican error. PMID- 8196761 TI - Making publication more respectable. PMID- 8196762 TI - Ras blooms on sterile ground. PMID- 8196763 TI - Hobgoblin of phylogenetics? PMID- 8196764 TI - Early diagnosis of Alzheimer's? PMID- 8196765 TI - Complete DNA sequence of yeast chromosome XI. AB - The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome XI has been determined. In addition to a compact arrangement of potential protein coding sequences, the 666,448-base-pair sequence has revealed general chromosome patterns; in particular, alternating regional variations in average base composition correlate with variations in local gene density along the chromosome. Significant discrepancies with the previously published genetic map demonstrate the need for using independent physical mapping criteria. PMID- 8196766 TI - The visual filter mediating letter identification. AB - We hear periodic sounds, or tones, by means of parallel auditory filters, each tuned to a band of temporal frequency, and we see periodic patterns, or gratings, by means of parallel visual filters, each tuned to a band of spatial frequency. Beyond helping us to see gratings, do these visual filters participate in everyday tasks such as reading and object recognition? After all, grafting visibility only requires the distinguishing of pattern from blank, whereas object recognition, for example letter identification, requires classification by the observer into one of many learned categories. Here we make use of results from hearing research, applying to vision a noise-masking paradigm that reveals the filter(s) mediating any threshold task. We find that letter-identification and grating-detection filters are identical, showing that the recognition of these objects at one size is mediated and constrained by a single visual filter, or 'channel'. PMID- 8196767 TI - Atonal is the proneural gene for Drosophila photoreceptors. AB - The Drosophila peripheral nervous system comprises four major types of sensory element: external sense organs (such as mechano-sensory bristles), chordotonal organs (internal stretch receptors), multiple dendritic neurons, and photoreceptors. During development, the selection of neural precursors for external sense organs requires the proneural genes of the achaete-scute complex, which encode basic-helix-loop-helix transcription factors. These genes do not, however, control precursor selection for chordotonal organs or photoreceptors, raising the question of whether other proneural genes exist or a different mechanism of neurogenesis operates. Here we show that atonal (ato), originally isolated as a proneural gene for chordotonal organs, is also the proneural gene for photoreceptors. Pattern formation in the Drosophila eye involves a succession of cell fate specifications. Of the eight photoreceptors within each ommatidium of the compound eye, the photoreceptor R8 is the first to appear in the eye imaginal disc, right behind the morphogenetic furrow. The appearance of other photoreceptors (R1-7) follows in a defined sequence that is thought to arise by induction from R8 (refs 8, 9, 11, 12). We find that photoreceptor formation requires the function of atonal at the morphogenetic furrow and that atonal is specifically required for R8 selection. Formation of other photoreceptors does not directly require atonal function, but does depend on R8 selection by atonal. Thus, photoreceptors are selected by two mechanisms: R8 by a proneural mechanism, and R1-7 by local recruitment. PMID- 8196768 TI - Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells. AB - It has been suggested that mutations within immunodominant cytotoxic T-lymphocyte (CTL) epitopes may be exploited by viruses to evade protective immune responses critical for clearance. Viral escape could originate from passive mechanisms, such as mutations within crucial CTL epitopes, either affecting major histocompatibility complex binding or T-cell antigen receptor (TCR) recognition. Additionally, it has recently been shown that substitutions of TCR contact sites can yield analogue peptides that can still interact with the T-cell receptor but be unable to deliver a full stimulatory signal, thus inducing anergy or acting as an antagonist for the TCR. We report here that hepatitis B virus isolates derived from two chronically infected patients display variant epitopes that act as natural TCR antagonists with the capacity to inhibit the CTL response to the wild type epitope. During natural infection, TCR antagonist mutations of CTL epitopes could contribute to the development of viral persistence, especially if the antiviral CTL response is monospecific or the epitope is strongly immunodominant. PMID- 8196769 TI - Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane. AB - A conserved tyrosine kinase-activated signal transduction pathway has recently been identified that comprises the plasma membrane-bound small guanine-nucleotide binding protein Ras and the protein kinases Raf, MAP-kinase kinase and MAP kinase. GTP-bound Ras interacts directly with the amino-terminal regulatory domain of Raf, but although Ras and Raf can be coimmunoprecipitated from ligand stimulated cells, Ras-GTP does not stimulate the kinase activity of Raf in vitro. Furthermore, we have failed to detect Ras in preparations of active detergent solubilized Raf, demonstrating that once it is activated, Raf does not require Ras. Whereas Raf is normally cytosolic, in cells expressing active Ras, Raf is associated with the plasma membrane. This led us to investigate whether Ras is required to localize Raf to the plasma membrane in order for Raf to become activated. We fused the membrane localization signal of K-Ras(4B) to the carboxy terminus of Raf. This protein is constitutively active and can be further activated by epidermal growth factor, independently of Ras. Our results indicate that Ras functions as a regulated, membrane-bound anchor for Raf, and that other signal(s) also contribute to Raf activation. PMID- 8196771 TI - Rapid arrayed filter production using the 'ORCA' robot. AB - By adapting a commercially available, general purpose laboratory robot, it is possible to produce high-density gridded hybridization filters of clone colonies or DNA products. We are using this system to produce 60-90, 8 x 12 cm filters in an 8-hour day, each containing 3,456 clones arranged in 96, 6 x 6 grids. PMID- 8196770 TI - Ras-dependent activation of MAP kinase pathway mediated by G-protein beta gamma subunits. AB - Mitogen-activated protein kinases, MAP kinases or ERKs (extracellular signal regulated kinases) are rapidly stimulated by growth-promoting factors acting on a variety of cell-surface receptors. In turn, ERKs phosphorylate and regulate key intracellular enzymes and transcription factors involved in the control of cellular proliferation. The tyrosine-kinase class of growth-factor receptors transmits signals to ERKs in a multistep process that involves Ras and a limited number of defined molecules. In contrast, ERK activation by G-protein-coupled receptors is poorly understood, as is the role of ras in this signalling pathway. We have explored in COS-7 cells the mechanism of ERKs activation by m1 and m2 muscarinic receptors, typical examples of receptors coupled through Gq proteins to induce phosphatidylinositol hydrolysis and to G(i) proteins to inhibit adenylyl cyclase, respectively. Here we present evidence that ERK activation is mediated by beta gamma subunits of heterotrimeric G proteins acting on a ras dependent pathway. PMID- 8196772 TI - Watershed for the structure of cytochrome c. AB - Redox-dependent changes in the position of bound water inside cytochrome c in solution may be important for its function as an electron transfer protein. PMID- 8196773 TI - [Behcet's disease]. PMID- 8196774 TI - [Diphtheria: a come-back?]. PMID- 8196775 TI - [The diphtheria epidemic in the Russian Federation and recommendations concerning diphtheria vaccination in The Netherlands]. PMID- 8196777 TI - [Exertion-related disorders in body temperature regulation in 8 participants in the Dam-to-Dam run 1993]. AB - In eight recreational runners (seven men and one woman, aged 16 to 50 years) participating in a 16 kilometer run, disturbances in thermoregulation were diagnosed. Six experienced sudden collapse without any prodromal signs, two were exhausted and had muscle spasms. Heat exhaustion was diagnosed in four runners, exertion-related hyperthermia in three and exertion-related heat stroke in one. As a complication the latter patient developed rhabdomyolysis with low grade intravascular coagulation and acute renal insufficiency. The most important therapy consists of cooling the patient, the most important preventive measures are wearing light clothing and drinking regularly during the run. PMID- 8196776 TI - [Submersion in children; the role of hypothermia and development of adult respiratory distress syndrome]. AB - OBJECTIVE: To evaluate the occurrence of the adult respiratory distress syndrome (ARDS), and of hypothermia as a predictor of outcome in cases of submersion injury in children. DESIGN: Retrospective analysis. PATIENTS: All drowning cases admitted to the Intensive Care Unit of the Wilhelmina Children's Hospital in Utrecht between January 1986 and January 1993. RESULTS: There were 45 patients, 29 boys and 16 girls, aged 0-13 years. Hypothermia was related to the duration of submersion and did not correlate with a good outcome. Asystole on arrival at the hospital was associated with demise in all but one patient, who was left with severe neurological impairment. ARDS occurred in 27/45 patients (60%), all within 6 h following admission. Of the 45 patients treated, 11 died. Of the 34 survivors, 7 were discharged from the Intensive Care Unit with neurological sequelae (2 with mild, 5 with serious sequelae). CONCLUSION: In our patients with drowning accidents, hypothermia did not appear to provide any protective effect. ARDS, if it occurred, became evident within 6 h after admission. PMID- 8196778 TI - [Paget's disease of the scrotum]. AB - Paget's disease was diagnosed in a scrotal biopsy specimen of a male aged 70 who for three years had had a red scaly skin lesion of the penoscrotal borderline area. Eight local excisions failed to achieve radical removal of the tumour. Before the 9th excision, the skin was pretreated with fluorouracil cream for 10 days. Ultimately, the lesion could be removed radically. Extramammary Paget's disease is a rare condition. There is no consensus on the strategy to be adopted. Surgical treatment appears indicated. PMID- 8196779 TI - [Internists in Europe]. PMID- 8196780 TI - [Atherosclerosis also caused by local vascular inflammation]. PMID- 8196781 TI - [Incidence and prevalence of genetically-determined disorders in The Netherlands; a literature study]. PMID- 8196783 TI - [Hepatitis A; an innocent childhood disease?]. PMID- 8196782 TI - [Medical secrecy does not count in AIDS patients]. PMID- 8196784 TI - [Who in The Netherlands is eligible for immunization with inactivated hepatitis A vaccine?]. PMID- 8196785 TI - [Correction of refractive disorders using lasers]. PMID- 8196786 TI - [Botulin in the treatment of vocal cord dyskinesias]. PMID- 8196787 TI - [Costs of hepatitis A prophylaxis in travelers]. PMID- 8196788 TI - [No positive effect of preoperative exercise therapy and teaching in patients to be subjected to hip arthroplasty]. AB - OBJECTIVE: To evaluate the benefits of preoperative physical therapy and instruction of patients with primary coxarthrosis to be subjected to a total hip arthroplasty. SETTING: University Hospital Maastricht. DESIGN: Controlled trial. MATERIAL AND METHOD: During 14 months the effects were measured of preoperative physical therapy and instruction of 64 patients divided into two populations; one group (n = 31) received preoperative instruction and physical therapy, the other did not (n = 33). Effects were measured with the Visual Analog Scale, the Harris Hip Score and the days patients could stand, walk, climb a stair and be discharged. RESULTS: The Harris Hip Score showed a significant difference (p < 0.05) favouring the instructed group on day 14 after the operation and at the moment the patients were discharged. The other parameters showed no significant differences between the groups. Differentiation by age, gender and type of arthroplasty showed the same results. CONCLUSION: Preoperative exercise and instruction is not useful for patients who in the near future will be treated with a total hip arthroplasty for primary coxarthrosis. PMID- 8196789 TI - [Limitations to care; evaluation of decision making concerning the death of 104 children in a surgical intensive care unit]. AB - OBJECTIVE: To analyse the decision-making process concerning withholding and withdrawal of life-sustaining treatment in children who died in a paediatric surgical intensive care unit. DESIGN: Retrospective evaluation of medical and nursing records from the period 1988-1992. SETTING: Sophia Children's Hospital University Hospital Rotterdam. METHOD: The evaluation concerned 104 children who died in the paediatric surgical intensive care unit during the study period. The causes of death were classified according to the classification proposed in a recent report issued by the Dutch Association of Paediatricians. A distinction was made between newborns and older children. RESULTS: In both newborns and older children, about half of the children had died because treatment was either withheld (4/104) or withdrawn (53/104). There were no cases of 'intentional termination of life in emergencies'. The remaining children had died in spite of medical treatment that had been considered worthwhile. CONCLUSION: The problems and guidelines suggested from the field of neonatology are applicable not only to newborns with severe congenital anomalies, but also to older children. Evaluation of the decision-making process should not be limited to medical-technical and nursing aspects, but should also include the experiences of the parents and the treatment team. PMID- 8196790 TI - [Care and experiences of 20 set of parents concerning the death of children in a surgical intensive care unit]. AB - OBJECTIVE: To gain insight into the attitude and experiences of parents concerning the death of children in a paediatric surgical intensive care unit of a University Children's hospital. DESIGN: Retrospective evaluation of records from 1988-1992, supplemented with semistructured interviews in the second half of 1992. SETTING: Sophia Children's Hospital-University Hospital Rotterdam. PATIENTS AND METHODS: The evaluation concerned 104 children. In 36 children death was a direct consequence of their illness, 11 died unexpectedly after an unsuccessful attempt at resuscitation, and in the remaining 57 treatment had not been initiated or had been withdrawn. Six months after the death of their child, twenty couples of parents of 20 children were asked after their experiences before, during, and after this death; in addition they were asked whether they would appreciate a longer contact with the hospital. RESULTS: Most parents chose to be present at the moment of dying. The parents generally highly appreciated the talks about the decision-making process and about coming to terms with the loss of their child, both with doctors and nurses. Most also appreciated a talk at some later time. CONCLUSION: The results from this study indicate that structured guidance of parents concerning their child's death in the form of a counselling programme, is advisable. PMID- 8196791 TI - [Sneddon's syndrome: an unusual cause of cerebral infarct at a relatively young age]. AB - Sneddon's syndrome was diagnosed in a man of 56, and two women aged 48 and 22 years. It is a rare disease characterised by the combination of skin lesions (livedo racemosa) and cerebral infarctions at a relatively early age. Apart from the clinical presentation, the diagnosis can sometimes be confirmed by a typical microscopical image of a biopsy taken from a region adjacent to the livedo (endothelitis, perivascular lymphocyte infiltration and hypertrophy of the artery wall). The cause of the syndrome is unknown and a specific therapy is lacking. Early recognition of Sneddon's syndrome may protect patients against unnecessary ancillary investigations. PMID- 8196792 TI - [Obstetrics and gynecology in the year 2000]. PMID- 8196793 TI - [Needs assessment for gynecologists/obstetricians up to the year 2005]. PMID- 8196794 TI - [Successful electroconvulsive therapy in a pregnant woman with malignant neuroleptic syndrome]. PMID- 8196795 TI - [Successful electroconvulsive therapy in a pregnant woman with malignant neuroleptic syndrome]. PMID- 8196796 TI - [Current composition of phenobarbital solution FNA could lead to convulsions]. PMID- 8196797 TI - [Legislation on Mass Screening]. PMID- 8196798 TI - [Positive effect of long-term coumarin treatment following a heart infarct]. PMID- 8196799 TI - [Current viewpoints in therapy and prognosis of chronic atrial fibrillation]. PMID- 8196801 TI - [Series of articles on current developments in medical education]. PMID- 8196800 TI - [Psychiatric disorders in women in the puerperium]. PMID- 8196802 TI - [Prevention of neonatal tetanus in developing countries hampered by local organization and limited knowledge of health personnel and traditional midwives; North Sulawesi (Indonesia)]. AB - OBJECTIVE: Evaluation of the policy to prevent neonatal tetanus in North-Sulawesi (Indonesia). DESIGN: Descriptive and questionnaire study. SETTING: Twelve villages in the district of Minahassa, Sulawesi, Indonesia. METHOD: The policy aimed at preventing neonatal tetanus was studied during the period April-June 1992. The relevant knowledge was tested of the community health workers (CHWs, n = 142) and traditional birth attendants (TBAs, n = 37) active in the 12 villages. To this purpose, 54 and 27 workers, respectively, were interviewed using a standard questionnaire. RESULTS: Not all women were vaccinated sufficiently to prevent their unborn children from tetanus; mostly, adequate vaccination records were lacking. 33% of the TBAs were unaware that neonatal tetanus can be prevented by hygienic delivery; in this respect there was no difference between trained and untrained TBAs. Of the CHWs, 39% were familiar with the correct vaccination policy and 26% did not know that pregnant women have to be vaccinated. 70% of the CHWs and TBAs wrongly believed that neonatal tetanus no longer occurred in their village. CONCLUSION: CHWs and TBAs showed little interest in neonatal tetanus, so that they were lacking in motivation regarding hygienic delivery procedures and preventive tetanus toxoid vaccination. Implementation of a good preventive programme in developing countries mostly requires organizatory rather than biomedical improvement. PMID- 8196803 TI - [Myiasis: wound infection caused by fly larvae in a nursing home]. AB - In a 66-year-old man, admitted to a nursing home in the summer for conservative treatment of wet gangrene of his foot, wound myiasis was diagnosed. Amputation below the knee was necessary. Flies laying eggs in necrotic wounds probably gained entrance to the patient's room through doors standing open. PMID- 8196804 TI - [SPIRIT: new life spirit for anticoagulant treatment in the secondary prevention of brain infarcts? A new study. Stroke Prevention in Reversible Ischaemia Trial]. PMID- 8196805 TI - [Which occupational groups run a real risk of tetanus infection in their work and should therefore be vaccinated against tetanus?]. PMID- 8196806 TI - [20,000 kg aspirin and 45 pages British Medical Journal]. PMID- 8196807 TI - Health reform: the Governor's perspective. PMID- 8196808 TI - Top 10 irrelevant arguments in the health care debate. PMID- 8196809 TI - The role of states in health reform. PMID- 8196810 TI - The need for health care reform in Nebraska. AB - This paper has identified some of the major health care problems in Nebraska. Although Nebraska does not face as many serious challenges as some other states, there is clearly a need for reform. For example, the health of our population is generally good, but many serious gaps exist, particularly for minority population groups. Per capita health care costs in Nebraska are only slightly below the national average, and out-of pocket costs for the average Nebraska family rank among the highest in the nation. In addition, Medicaid costs are exploding and create serious challenges to balancing the state's budget. Nearly 140,000 Nebraskans lack health insurance coverage and at least 90,000 others are underinsured. Many insurance policies limit or deny coverage to individuals with pre-existing medical conditions, deny coverage to individuals employed in certain occupations, and limit coverage for preventive services. "Cost shifting" continues to become more widespread, which significantly increases the number of small businesses that drop or reduce health insurance coverage for their employees. Finally, rural areas face some unique challenges related to their ability and capacity to provide services. There is a serious shortage of primary care physicians, mid-level practitioners, and many other allied health professionals. As a result, individuals, including a large elderly population, must travel long distances to obtain care. Many rural hospitals are under severe financial stress and some will close during the next five years. There appears to be an adequate supply of nursing home beds in rural areas, but many communities lack adequate in-home services. PMID- 8196811 TI - Health care in Nebraska. PMID- 8196812 TI - Health care problems and Nebraska solutions. PMID- 8196813 TI - The impact of health system reform on academic health centers. PMID- 8196814 TI - Medical education: leadership and adaptation in a changing world. AB - Health care reform has remarkably accelerated in recent years and is now being driven by economic considerations more than by any others. There have been great changes in medical effectiveness, practice and, in consequence, medical education. These trends will continue and accelerate even more if comprehensive health care reform is achieved. Health care is highly valued by our society and medical education is an integral and essential part of health care. The challenge for health professions educators is to lead constructive change and to adapt to changes imposed by systemic reform to assure that the quality of our graduates enables them to best serve society. PMID- 8196815 TI - The position of the providers--physicians. AB - As the AMA has been on the cutting edge in discussions of health care reform nationally, so the NMA has been intimately involved in such discussions in Nebraska. As the "umbrella" organizations for physicians nationally and statewide, respectively, the AMA and NMA recognize that there is no easy and painless solution to the crisis. Indeed, there is still sharp division of opinion among medical specialty societies regarding even the most fundamental issues of health care reform. From a state perspective, the NMA pledges to continue to work with other health care organizations, insurance organizations, and governmental entities to identify the health care reform measures that best suit the needs of the citizens of Nebraska, within the constraints that national health care reform will allow for individual state initiatives. While physicians of Nebraska want a "place at the table" to discuss health care reform, it will be the challenge for the NMA to assure that physicians and the patients they serve do not become "part of the meal". PMID- 8196816 TI - The health care delivery system: present problems and future directions. PMID- 8196818 TI - The future of health care reform. PMID- 8196817 TI - Nebraska, the health care good life. PMID- 8196819 TI - RBRVS: unfinished business. PMID- 8196820 TI - HELLP syndrome: a variant of severe preeclampsia. PMID- 8196821 TI - What is the prevalence of clinical diabetic nephropathy? PMID- 8196822 TI - Perioperative diabetes regulation with the help of a standard protocol. AB - According to a standard protocol 115 patients (96 type 2 DM, 19 type 1 DM) were treated with a 3 litre glucose 5%/day infusion, KCl and insulin, with the aim of obtaining near-normoglycaemia perioperatively. Blood glucoses of 6.7-10.0 mmol/l were scored as ideal, 3.5-15.0 mmol/l as acceptable, and the remaining values as unacceptable. In 32 patients (28%) the protocol was followed in all aspects, whereas in 45 patients (39%) the protocol was followed in therapeutic aspects (total n = 77.67%, Group 1). In the remaining 38 patients (33%) protocol violations occurred (Group 2). In 48 patients (62%) of Group 1 ideal or acceptable control was obtained perioperatively versus 11 patients (29%) of Group 2 (p < 0.05). In patients with good preoperative long-term regulation (HbA1 < or = 8.0%; n = 81) ideal or acceptable perioperative control was achieved in 58% (n = 47) versus 13% (n = 4) of those (n = 31) with preoperative HbA1 > 8.0% (p < 0.05). Stepwise multiple logistic regression analysis showed that preoperative long-term regulation (HbA1; p < 0.001) and adherence to the protocol (p = 0.022) were the only independent variables with prognostic significance for perioperative blood glucose control. In 17 patients (15%) minor electrolyte disturbances occurred. No patient had frank ketosis. Duration of disease, presence of complications, type of anaesthesia and operation did not affect perioperative diabetes control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196823 TI - Erythromycin-induced torsades de pointes and ventricular fibrillation in a patient with Legionella pneumonia. AB - Several case reports of erythromycin-induced torsades de pointes (TDP) arrhythmia have been reported in the literature. However, this potentially lethal side effect of a frequently prescribed drug is not generally known. We report a patient who developed TDP followed by ventricular fibrillation during rapid infusion of erythromycin lactobionate. Although the patient used diuretics, probably predisposing her to arrhythmias due to hypokalaemia, several ECG abnormalities predisposing to TDP, all related to erythromycin infusion, occurred during observation in the ICU, establishing the precipitating role of erythromycin. The diagnosis was made only after QT prolongation, TDP and ventricular fibrillation were observed during rapid intravenous infusion of erythromycin lactobionate, one of the reasons no doubt being the assumed lack of serious side-effects of this frequently prescribed drug. PMID- 8196824 TI - Cytochrome b5 reductase deficiency, an uncommon cause of cyanosis. AB - A patient with cyanosis due to methaemoglobinaemia caused by cytochrome b5 reductase deficiency is described. Investigation of his family confirmed transmission of this disorder as an autosomal recessive trait. The consequences of this rare condition are discussed. PMID- 8196825 TI - Long-term oxygen therapy. AB - This review discusses the different aspects of long-term oxygen therapy (LTOT). In selected patients with chronic hypoxaemia, LTOT may increase the life-span and quality of life. Since identification of these patients is both important and difficult, the indications for LTOT are discussed. Next, the appropriate time at which LTOT should be initiated is discussed in the section on the physiological criteria. Even in patients who qualify for LTOT, the effectiveness of this therapy may vary. Because they are important in this context, the prescription guidelines are considered. Finally, possible ways of increasing the efficiency of LTOT are reviewed in the sections on home oxygen systems, oxygen-conserving methods and the organization of LTOT in the Netherlands. PMID- 8196826 TI - [Radiosurgery of arteriovenous malformations]. PMID- 8196827 TI - [Clinical study on the recurrence of meningiomas: correlating factors for the recurrence and therapeutic prognosis of meningiomas]. AB - Authors have studied 128 cases of meningiomas which were operated on and examined histologically. 12 cases (11.3%) of 106 cases of the meningiomas followed up for more than 5 years after surgery had recurrence after the primary operation. The distribution of age and sex, the tumor location, the histological type, the extent of tumor evacuation and AgNORs counts and BrdU labeling index for the evaluation of tumor proliferation were studied comparatively in the two groups, the recurrent and nonrecurrent meningiomas. 8 cases (19.0%) of 42 cases of the meningiomas in the age-group lower than 50 years old were recurrent cases, whereas 4 cases (6.0%) of 67 cases in the age-group over 50 years old were non recurrent. Concerning the sex distribution of the meningiomas in our cases recurrent rate was 20.5% among males and 6.0% among females. The tumor locations of the meningiomas did not correlate significantly with recurrence. The extent of tumor removal demonstrated Simpson grade I (47 cases), grade II (37 cases), grade III (17 cases), grade IV (5 cases) on primary operation. Recurrence was found in 11 cases (13.1%) of 84 cases operated on by total removal of Simpson grade I or grade II. 8 cases of 11 cases had recurrence within 5 years after the primary operation of Simpson grade I or II. Total removal of the tumor was important in order to bring about long survival after operation. But correlation between the extent of tumor removal and recurrence was not able to be recognized. Histologically, all of the malignant, atypical and papillary type of meningiomas treated in the primary operations had recurrence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196828 TI - [Angiographical frequency of unruptured incidental intracranial aneurysms]. AB - We reviewed cerebral angiograms studied between May 1985 and December 1992 focusing on unruptured incidental intracranial aneurysms. In a total of 605 cases of cerebral angiograms except for patients with SAH, 43 patients (7.1%) were found to have unruptured aneurysms. In the 72 patients with headache, 11 patients (15.3%) were found to have unruptured aneurysms. This high frequency of unruptured aneurysms in headache patients is significant as a factor showing that headache may be due to unruptured aneurysms. The result of this observation is that as a screening study for headache patients, cerebral angiography may be required in spite of the invasive and high-risk method. But we think that MR angiography is, at present, a useful screening study only for detecting cerebral aneurysms with a diameter of over 5mm, and which are considered to need an operation. PMID- 8196829 TI - [EC-IC bypass surgery using saphenous vein graft: technical improvement in our experience]. AB - We managed ten cases of EC-IC bypass using a vein graft; six cases with multiple cerebral arterial occlusion and four cases with aneurysm necessitating therapeutic occlusion of the parent artery (Table). Patency of the graft was confirmed in seven cases on long-term follow-up ranging from 7 months to 5 years. Of the ten cases, two died within 7 days after surgery from causes unrelated to the bypass and one was lost in follow-up surgery. Hemorrhagic infarction was observed in two cases, one of which underwent removal of the hematoma. In five cases with cerebral occlusive disease, there were no additional ischemic events and two cases with giant aneurysms showed improvement of visual acuity and extraocular movement. We improved on several surgical techniques for vein graft. We used small hemoclips to occlude branches of the saphenous vein instead of ligating them, which shortens the harvesting time of the saphenous vein. Vessel cannula with a small-sized elegant tip and one-directional valve (DLP, INC., USA) was also used to inflate or deflate vein grafts with saline. It was easily attached to the graft and minimized air entrapment in the lumen. Small clips for microvascular anastomosis (Mizuho INC., Japan) were used to temporarily occlude branches or perforators from the recipient artery. One of the branches of the graft was dissected long enough, through which intraluminal air or thrombus was washed out at the final stage of the surgery. These procedures are useful for shortening occlusion time of the recipient artery and decreasing the risk of embolism. PMID- 8196830 TI - [Evaluation of angiographic delayed vasospasm due to ruptured aneurysm in comparison with cerebral circulation time measured by IA-DSA]. AB - Delayed vasospasm due to ruptured aneurysm has been basically evaluated by angiographic changes in contrast to clinical features such as delayed ischemic neurological deficits (DIND). However, the discrepancies between angiographic and clinical findings have been pointed out. In this study, angiographic changes and cerebral circulation time in ruptured aneurysms were simultaneously investigated with IA-DSA. Thirty-two patients, who had ruptured aneurysms at the anterior circle of Willis and neck clippings at the acute stage, were investigated. Carotid angiogram was performed with IA-DSA on the 7-13th day after the attack. Angiographic changes were evaluated by Fischer's classification and circulation time was calculated in the following way. A time-density curve was obtained at the two ROI's; the C3-C4 portion and the rolandic vein. Circulation time was defined by the difference between the time showing peak optical density at the carotid and the venous portion. The control value of this circulation time obtained from 20 cases with non-rupture aneurysm and epilepsy was 3.4 sec (53 year old) on the average. X-ray CT scan examination was performed at the same time and clinical features were observed everyday. Angiographically, 3 cases were free from vasospasm, 18 cases were found to present slight to moderate vasospasm, and 11 cases showed severe vasospasm. Circulation time in patients with no spasm was 3.6 seconds, in patients with slight to moderate vasospasm it was 4.3 seconds and in patients with severe vasospasm it was 6.8 seconds. Ten patients showing cerebral infarction on CT scans demonstrated significantly long circulation time, 7.0 second on the average.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196831 TI - [Microsurgical anatomy of the anterior communicating artery and its perforating arteries important for interhemispheric trans-lamina terminalis approach: analysis based on cadaver brains]. AB - Microsurgical anatomy of anterior communicating artery (ACoA) and its perforating arteries important for interhemispheric trans-lamina terminalis approach is examined in 25 cadaver brains under magnification using a surgical microscope. ACoA were found in all cases but 60% of those cases had variations such as plexiform ACoA, dimple ACoA, fenestrated ACoA, triple A2 and azygous ACA. In cases with variations such as plexiform ACoA, triple A2 and azygous ACA, it seems difficult to section and divide the ACoA to obtain a better operative field. Perforating arteries of ACoA were noted in all cases. They were classified into the subcallosal artery, hypothalamic artery and chiasmatic artery according to caliber, origin, course and termination. Among these three arteries, subcallosal artery is thought to be an offending artery in memory impairment, character change and psychological abnormalities, because it terminates at the bilateral subcallosal areas. We stress in this paper that the subcallosal artery is the most important perforating artery of ACoA and the incidence of variations of ACoA is higher than previously reported. PMID- 8196832 TI - [A case of multiple myeloma associated with a large subcutaneous mass in the frontal region]. AB - A case of multiple myeloma having plasmacytoma in the frontal bone and clivus is reported. A 68-year-old female was referred to our hospital because of a subcutaneous mass in the frontal region. She was diagnosed as having multiple myeloma 7 years ago and had been treated with chemotherapy. On admission, severe anemia, hyperproteinemia and elevation of serum lambda type immunoglobulin G (IgG) were pointed out. Plain skull X-rays showed numerous punched out lesions with a large bone defect of the frontal bone. CT scan and MRI revealed a mass lesion in the clivus in addition to a large epidural tumor in the frontal region. The encapsulated frontal epidural tumor was totally resected and cranioplasty was performed with resin. Histological diagnosis was plasmacytoma of IgG lambda type. The postoperative course was uneventful, and chemotherapy was continued. There was no tumor recurrence in the frontal region and no neurological deterioration, but she died of DIC 15 months after the operation. Twenty seven cases in the literature of multiple myeloma forming cranial or intracranial plasmacytoma were briefly reviewed. Although the prognosis of such cases is poor, total resection of medullary plasmacytoma is warranted especially in multiple myeloma patients who don't have another extramedullary plasmacytoma or plasma cell leukemia. PMID- 8196833 TI - [A case of mesenchymal chondrosarcoma in the orbit]. PMID- 8196834 TI - [Mixed angioma of the brain: report of two cases]. AB - Clinical features of two patients with mixed angiomas are presented. One patient with a cerebral venous angioma with arterial components was successfully treated with radiation therapy; and the other, who had a common draining vein with cerebellar arteriovenous malformation and venous angioma, was treated with surgical removal of the arteriovenous malformation. These two cases suggested that there is a similarity between the pathogenesis of arteriovenous malformation and venous angioma in the brain. PMID- 8196835 TI - [A case of dural type of histiocytosis X presenting as a mass lesion in the tentorium cerebelli]. AB - Histiocytosis X is a disease of unknown etiology, characterized by a mass of proliferating histiocytes, plasma cells and inflammatory cells foaming a granuloma within the reticuloendothelial elements of any organ in the body. In the central nervous system (CNS), hypothalamic disorder of histiocytosis X is often found, but histiocytosis X in other regions is quite rare. We report a case of a 5-year-old girl with histiocytosis X of the zygoma presenting as a mass lesion in the tentorium cerebelli. A computed tomographic (CT) scan demonstrated a tumor at the left tentorial region, extending along the dura mater of the tentorium cerebelli. Magnetic resonance imaging (MRI) revealed a low signal intensity region on both T1 and T2-weighted images. MRI with Gd-DTPA showed a homogeneous enhanced mass extending to right and inferior sites with a thickened tentorium. As the thickened dura matter continued from the left middle fossa to the mass lesion, the tumor was considered to arise from the left zygoma and extend to the tentorium cerebelli. CNS extension of histiocytosis X is manifested either as (1) the cerebral type or (2) the dural type. Many cases of cerebral type histiocytosis X including hypothalamic disorder have been reported. Only 6 cases of the dural type of histiocytosis X have been described. Although the lesions of the cerebral type of histiocytosis X show prolonged T1 and T2 values on MRI, the MRI findings of the dural type have not been reported. The present case is the first report of the appearance of the lesion on MRI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196836 TI - [Penetrating craniocerebral injuries during downhill skiing]. AB - Two cases of penetrating craniocerebral injuries which occurred during alpine skiing were presented. The first was a 25-year-old lady whose calvarium was impaled with a ski pole in the anterior part of the orbital roof following an interpersonal collision. She was brought to the Critical Care and Emergency Center, Iwate Medical University. On admission, her consciousness was clear and a stab wound was observed in her upper eyelid. Initial CT showed bone fracture of the anterior part of the orbital roof and a small intracerebral hematoma associated with bone fragment was revealed. Immediate removal of the hematoma and foreign body was carried out and duralplasty was performed. She had a very good postoperative course but residual anosmia. The second was a 9-year-old boy who lost control and collided with a tree during downhill skiing. A twig penetrated through his left maxillary sinus. He was brought to the Critical Care and Emergency Center, Iwate Medical University. On admission, his consciousness was clear. CT showed a round low density area from his anterior lobe to the Nucleus caudatus, indicating the tract of the twig. Immediately, duralplasty and removal of the foreign body was performed. He had a very good postoperative course.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196837 TI - [Postlaminectomy kyphosis of the cervical spine complicating spinal cord tumor in the foramen magnum]. AB - Postlaminectomy kyphosis is rarely encountered as a sequela of decompression of the upper cervical spine, especially in adults. We present a case of disabling cervical kyphosis which developed after laminectomy for excision of a foramen magnum tumor and was treated successfully by occipito-vertebral fusion. A sixty one-year old female was treated by laminectomy of the first through to the third cervical spine for a foramen magnum meningioma. One year later, the laminectomy was extended downward to include the fourth through to the seventh cervical spine because of neurological deterioration. Seven years after the first laminectomy, she was referred to our spinal service because of severe neck pain, numbness and muscle weakness of both upper extremities. Lateral X-ray of her cervical spine presented a severe kyphosis. Roentgenogram two months after the first laminectomy already showed slight deformity and, timewise, it corresponded with the time when the patient experienced neurological deterioration. Subsequent X-rays showed progression of kyphosis. After we confirmed a lessening of the pain and improvement of the neurological symptoms during an axial traction using a halo vest, posterior occipito-cervico-thoracic fusion was performed using Luque segmental spinal instrumentation and autogenous bone graft. After surgery the pain decreased and neurological symptoms improved. It is important to be aware of the complication of kyphotic deformity after laminectomy and once it has developed, it is recommended to stabilize the progression by early spinal fusion. PMID- 8196838 TI - [A case of intracranial arteriovenous malformation presenting with intracranial hypertension]. AB - A case of unruptured arteriovenous malformations (AVMs) presenting benign intracranial hypertension is reported. A 14-year-old male suffered from headache and papilledema. Intracranial pressure was 260 mmH2O. Unenhanced CT demonstrated no evidence of hemorrhage or hydrocephalus. Angiogram demonstrated a large AVM in the left temporal lobe supplied by the left posterior cerebral artery and left middle cerebral artery. It drained into the transverse sinus. Surgical excision of the AVM eliminated the headache and papilledema. AVM causes hemorrhage in 50% of cases, seizure in 30%, and other focal neurological deficits in 20%. Benign intracranial hypertension is an uncommon effect of unruptured AVMs. Only 13 cases have been reported in the literature. Benign intracranial hypertension associated with unruptured AVMs occurs in young patients with high flow AVMs that drain into the major sinus. The mechanism of intracranial hypertension associated with unruptured AVM is unknown. However, there are several possible mechanisms of intracranial hypertension associated with unruptured AVMs. The arterial blood shunting into a major sinus impedes venous return from the surrounding brain. That causes the increase of cerebral blood volume and the elevation of sinus pressure. This mechanism would reduce CSF absorption and would increase intracranial pressure. Pharmacological therapy is ineffective in controlling intracranial hypertension. Surgical excision of AVM effectively reduced intracranial hypertension. Thus, surgical excision of AVMs, if it can be done with low risk, is the treatment of choice to decrease intracranial hypertension in patients with unruptured cerebral AVMs. PMID- 8196839 TI - [A case of aspergillosis presenting marked granulomatous pachymeningitis]. AB - The authors report a rare case of intracranial aspergillosis presenting marked granulomatous pachymeningitis. A 58-year-old male who had a three-year history of diabetes and chronic bronchitis was referred to us because of progressive left hemiparesis and dysarthria. Postcontrast CT scan showed a ring-enhancing lesion with marked perifocal edema in the right parietal lobe, and right subdural enhancing mass. MR image revealed hypertrophic dura mater in the right convexity. On June 9, 1992, partial removal of the intra-axial cystic mass and granulomatous dura mater was performed. A number of characteristic aspergillus hyphae were recognized in the resected cyst and granulomatous dura mater. Postoperatively, the patient was treated with amphotericin-B and fluconazole. But granulomatous pachymeningitis became progressively enlarged and eventually created a large mass effect again. On January 23, 1993, the patient died of pneumonia. Cerebral aspergillosis is getting common but preoperative diagnosis is still difficult because of its causing several clinical features such as brain abscess, granuloma, intracerebral hemorrhage, cerebral infarction, meningitis, and encephalitis. Several comments were made about the pathogenesis of these features, and the necessity of early diagnosis and treatment was emphasized. PMID- 8196840 TI - [Ruptured anterior communicating artery aneurysm associated with inter-optic course of anterior cerebral artery: report of a case and review of the literature]. AB - We report a ruptured anterior communicating artery (ACoA) aneurysm in a patient whose anterior cerebral artery (ACA) arose from the left C3 portion and ascended between the optic nerves. A 50 year-old woman was admitted to our department with complaints of headache and vomiting. CT scan showed thick subarachnoid hemorrhage. Left carotid angiography revealed a saccular aneurysm of the anterior communicating artery and an abnormal vessel which arose from the left C3 portion and terminated in the territory of the ACoA. Surgery was performed about eight hours after subarachnoid hemorrhage. The abnormal vessel was identified as it ascended between the optic nerves. There are only 25 reported cases of this abnormality including our own case. The right carotid artery was the most frequent origin of the abnormal artery (18 cases). 13 aneurysms were associated in 11 cases, in which seven were located in the anterior communicating artery. It was the most frequent site of the aneurysm. There were various explanations for this anomalous ACA. Because of the angiographical and operative findings, we prefer to use "inter-optic course of ACA" as the medical terminology better suited to describe this condition. PMID- 8196841 TI - [Hemicrania: comparison of physiopathogenetic theories]. AB - The authors tackle the complex question of the physiopathogenesis of migraine by examining the various theories which have been proposed, underlining that only through an open and constructive comparison it is possible to reach a real understanding of such a complex pathology such as migraine. PMID- 8196842 TI - [Primary hyperaldosteronism caused by small adenoma not visible with CAT using typical postural studies for hyperplasia. Report of a case]. AB - The paper describes a case of primary hyperaldosteronism using typical postural tests for hyperplasia and negative CAT, elements which in the majority of cases allow an adrenal gland hyperplasia to be confirmed, but which should not overlook the rare but documented possibility of a small adenoma not visible with CAT, responding to angiotensin II and which can be treated with surgery. PMID- 8196843 TI - [Malignant mesenchymal tumors of the breast. Report of 3 new cases]. AB - Malignant tumors of the breast arising from the connective tissue of the gland are rare and underestimated. Three new cases are here reported: 1 malignant fibrous histiocytoma and 2 malignant phylloides tumors. Tumor size, mammographic findings and cytologic aspect of the needlebiopsy lead to the correct diagnosis. Large excision or radical mastectomy are treatments of choice, while axillary lymph nodes dissection does not appear justified, since metastatic spread via lymphatics is rare. Postoperative radiation and chemotherapy seem not effective in preventing local recurrences. PMID- 8196844 TI - [Bell's palsy in HIV infection]. AB - Neurological complications represent one of the most important causes of morbidity and mortality in patients with HIV infection or AIDS. The peripheral nervous system is frequently involved in different stages of HIV disease, and the etiopathogenetic mechanisms are various. Idiopathic peripheral facial nerve palsy (Bell's palsy) has been considered by several Authors as one of the possible neurologic complications of HIV infection, mainly described in the early stages. As a matter of fact when facial palsy onsets in the late stages of the disease, when there is a severe immunodeficiency, usually is secondary to opportunistic infections, polyradiculopathy, or tumors involving the nervous system. To our knowledge, in the current literature there are few clinical studies reporting facial palsy associated to HIV infection. Since 1986 till 1992 three HIV infected patients with Bell's palsy have come to our observation. All three of them were asymptomatic (CDC II) and in one of them was the first clinical manifestation indicating HIV infection. The palsy in this patient and those reported by others was self-limiting with a good prognosis. PMID- 8196845 TI - [Headache: new epidemiologic and nosographic trends]. AB - Most recent epidemiological data on headaches are here discussed. These data clearly show the great social-economic importance of this problem, giving at the same time many hints of discussion on the different aspects of this complex syndrome. It is here also analyzed the latest international classification of the headache. PMID- 8196846 TI - [Major histocompatibility complex antigens in a population of insulin-dependent diabetics living in the Province of Varese]. AB - The HLA haplotype was studied in 143 newly diagnosed insulin-dependent diabetic subjects resident in the province of Varese who attended the clinic between March 1987 and June 1993. The frequency with which the various loci of the histocompatibility system were observed was compared with that reported in 83 non diabetic subjects not related to the diabetics taking part in the study. The relative risk (RR) was calculated using these data and its statistical significance was assessed using the chi-square test. 70.6% of subjects were positive for loci DR3 or DR4, whereas only 7.7% (11 subjects) were found to be carriers of eterozygous DR3-DR4. This percentage is lower than that generally reported in the literature. However, even in the authors personal experience heterozygous DR3-DR4 subjects represent the greatest relative risk in absolute terms (RR = 14.49). The presence of antigen DQw2 is strongly indicative of the disease, both when it is found in an isolated form and in association with DR3 or DR4 (RR = 2.56, 4.03, 3.29 respectively). The DR3/DR4/DQw2 axis gives a RR of 9.17. The associations of B8/DR3/DR4 and B8/DR3/DQw2 give a RR of 9.17, whereas the B8/DR4 axis gives a RR of 10.47. In this series, the lowest risk of developing the disease was provided by the DR2/DR7 axis (RR 0.28); DR2 alone gave a RR of 1.84 and DR7 alone gave a RR of 0.62. The discrepancies reported with the literature may be related to ethnic variations, thus giving added weight to the hypothesis of the heterogeneity of insulin-dependent diabetes mellitus. PMID- 8196848 TI - [Mucoregulatory therapy in secreting disease of the middle ear]. AB - A controlled double-blind study was carried out vs placebo to evaluate the preventive and therapeutic efficacy of carboxymethylcysteine lysine salt (SCMC Lys) in 40 non-adenoidectomised children (aged between 6-7 years old) with secretive otitis media and in 30 adult patients with acute inflammatory pathologies of the middle ear. The drug SCMC-Lys was administered to children at a dose of 750 mg/die in a linctus formula for 10 days and 2.7 g in a granular formula once a day for a maximum of 15 days if recovery had not already occurred. All subjects were assessed before and after treatment by means of an anamnestic and objective otological examination, tympanometry, nephelometric tests for IgA and mucociliary transport time. SCMC-Lys eliminated hypoacoustic symptoms in 85% of children treated with SCMC-Lys and in 35% of those treated with placebo. PMID- 8196847 TI - [Increase in absolute atmospheric pressure in hyperbaric chamber in cirrhosis with ascites: lack of natriuretic response and increase of atrial natriuretic peptide]. AB - In normal subjects increasing atmospheres of absolute pressure (ATA) on the cardiopulmonary system, in a hyperbaric chamber, results in a marked diuresis and an increase of circulating concentration of atrial natriuretic peptide (ANP). The present investigation was designed to determine the effect of ATA in a group of 5 sodium-retaining cirrhotic patients on hydro-saline balance, renin-angiotensin aldosterone system and ANP. After seven days on a 10 mEq sodium intake, each patient was studied on both a control and experimental (4-hour stay at 2-ATA in hyperbaric chamber) day. On each day, measurement of the following were obtained: plasma ANP, plasma renin activity (PRA) and aldosterone, electrolytes, creatinine clearance, volume and sodium and potassium urinary excretion. The increasing ATA lacked to induce both diuresis, natriuresis and increase in ANP plasma concentration. In these patients baseline, pre-hyperbaric, mean levels of PRA, aldosterone and ANP were 15.5 +/- 11.5 ng/ml/h, 808.4 +/- 360 pg/ml, 86 +/- 10.1 pg/ml, respectively, and were significantly elevated compared with normal range for control subjects without sodium restriction. In conclusion, increasing pressure at 2-ATA, in a hyperbaric chamber is unable to elicit both diuresis and natriuresis as well as modification on ANP and renin-angiotensin-aldo-sterone system in sodium-retaining cirrhotic patients. PMID- 8196849 TI - [Fast-dissolving sublingual tablets of piroxicam versus naproxen in the treatment of recurrent acute osteoarthrosis. Multicenter clinical trial]. AB - An open comparative study was carried out to evaluate the efficacy and safety of piroxicam FDDF, for sublingual administration, versus naproxen in the treatment of osteoarthritis. Sixty-one patients with acute-phase osteoarthritis involving various joints are reported. They were treated with 20 mg/day piroxicam FDDF or with 1000 mg/day naproxen for a total of 4 weeks. Drug efficacy was evaluated on the base of the variation of spontaneous pain, pain on motion, functional limitation and capacity to perform a specific activity. The intensity of spontaneous pain on the first day showed a statistically significant improvement with both drugs, but the onset of analgesia was only after 15 minutes with piroxicam and after 1 hour with naproxen. The improvement in pain intensity increased on the first day and until the 7th day with both drugs, but the comparative analysis between the analgesic efficacy of the two treatments proved to be favourable to piroxicam. On the 7th day, pain on motion and the capacity to perform a specific activity showed a statistically significant improvement with both drugs, but the comparative analysis between the two treatments proved to be favourable to piroxicam. The two drugs showed the same efficacy in functional restriction. The local and systemic tolerability of piroxicam was good. Only 5 patients experienced 6 systemic side-effects, and 1 patients showed local side effects, but 11 patients of the naproxen group showed 12 systemic side-effects. Thus piroxicam showed a better analgesic and anti-inflammatory efficacy than naproxen. Piroxicam proved to have a better systemic tolerability than naproxen. The local tolerability of piroxicam FDDF was good. PMID- 8196850 TI - [Fluoxetin combined with cyclobenzaprine in the treatment of fibromyalgia]. AB - The aim of this study is to evaluate the effectiveness of fluoxetin associated with cyclobenzaprine vs cyclobenzaprine in the treatment of fibromyalgia. Twenty one females with fibromyalgia were randomly assigned to 2 groups: group A (11 patients) was treated over 12 weeks with fluoxetin (20 mg/die) and cyclobenzaprine (10 mg/die), group B with cyclobenzaprine (10 mg/die). Basally and after 12 weeks patient self-assessment of pain, number of painful tender points, tender points index and morning stiffness were evaluated. The study has shown a significant improvement of the examined parameters in both treatment groups; however the comparison between the two groups showed a greater effectiveness, statistically significant, of the treatment with Fluoxetin associated with cyclobenzaprine. PMID- 8196851 TI - If there is a single constant in today's complex, tumultuous, turbulent health care systems, it is the state of continuous change. PMID- 8196852 TI - Change stimulates a diversity of responses among individuals and groups and in society. PMID- 8196853 TI - Nursing leadership: to thrive in a world of change. AB - Change is becoming the norm in health care environments. Nurse executives in leadership positions are an essential part of an institution's ability to adapt successfully and flourish with change. It is important for the nurse executive to have a clear concept of leadership, the change process, and organizational cultures. This will allow the nurse executive to create an environment within the organization where change is seen in a positive manner and staff are empowered to meet the challenges of health care today. PMID- 8196854 TI - Patient and staff needs drive changes on a postsurgical unit. AB - In response to a dynamic health care environment and influenced by fiscal pressures, "business as usual" on the postsurgical unit at University of Nebraska Medical Center required examination. Both internal and external factors prompted a staff-driven task force to plan and implement changes. The task force consisted of representatives from staff and management to redesign current practices collaboratively. Issues addressed were nursing workload, responsibilities, scheduling, patient satisfaction, job satisfaction, and professional development. Expected outcomes of changes in the work design on the unit centered on increased efficiency of nursing time, cost effectiveness, and increased satisfaction of patients and nursing staff. The task force proposed and implemented innovative changes in the report and documentation system, utilization of nonprofessional staff, and redesign of work hours. The article presents these changes in the work environment and focuses on a written report system and a clearly defined role for nonprofessional staff. PMID- 8196855 TI - Breakpoints and continuities: a case study of reactive change. AB - In 1987, nursing administrators effected radical changes on a pediatric psychiatry ward: A bachelor's degree in nursing science became mandatory for nursing staff, family systems nursing was introduced, and postdischarge nursing follow-up was instituted. To convey how they accomplished the changes, a case history of change on the ward is presented. It suggests that there were many driving forces. Factors most important to nursing's success included a strong vision of nursing, sufficient pain or discomfort to motivate change, the ability to recognize and seize opportunities, and the linking of change to existing institutional practices, policies, and values. PMID- 8196856 TI - Management style and staff nurse satisfaction in a changing environment. AB - In today's changing health care economic climate, attaining increased productivity of staff nurses without increasing costs is desirable. Employing a management style conducive to staff nurse job satisfaction may be one method. The article describes the findings of a research survey on perceived and desired nurse management styles and their relationship to staff nurse job satisfaction. A positive correlation (r = .48, p = .0001) was found between perceived management style and staff nurse job satisfaction. The closer the management style was to the participative group management style, the higher the level of staff nurse job satisfaction. PMID- 8196857 TI - Getting to X. AB - Just as there exist many forces driving the need for change on many fronts in health care, there are corresponding forces, some equally strong, that resist the change. The article presents a model for nurse executives to help them understand the predominant forces of change. The article also emphasizes the importance of organizational politics in the change process. PMID- 8196858 TI - Managing change wrought by advancing technology. PMID- 8196859 TI - Preimplementation financial evaluation of a structural work change: cost analysis of an innovative staffing schedule. PMID- 8196860 TI - Change champions at the grassroots level: practice innovation using team process. AB - A nursing administrative group recognized the critical value of staff participation in the formulation of a restructuring project and guidance throughout the project. Using a team approach, a task force of three staff nurses, two assistant nurse managers, a nurse clinician, a nursing practice specialist, and a representative from nursing administration came together. They were given responsibility for researching and setting the course for restructuring change. A unit-based team including a unit secretary, a nursing attendant, licensed practical nurse (LPN), and six staff nurses was formed from volunteers from the 40-bed medicine unit to develop that unit's plan for restructuring. The unit-based team analyzed patient care needs and staff member roles. They created a new patient care technician role as well as a nurse care coordinator role. The role of the LPN was envisioned as providing technical support. Staffing mix was also determined by the unit-based team. Both the task force and the unit-based team continue to evaluate, troubleshoot, and take every opportunity to sell their vision to solidify it further as the foundation for the future of patient care services at the hospital. The process will soon move forward to a large surgical unit. PMID- 8196861 TI - The contraceptive practices of women seeking termination of pregnancy in an Auckland clinic. AB - AIM: The aim of the study was to assess the contraceptive knowledge and practices of women attending the abortion service at Epsom day unit, Green Lane Hospital. METHODS: Women attending the unit in December 1992 and January 1993 were asked to take part in the study. A questionnaire was administered to consenting women to assess demographic details and previous contraceptive education. If a contraceptive method was used the reason for failure was explored and if no method was used the reason for non use was explored. RESULTS: Sixty-one percent of women were using a contraceptive method in the month of conception. The condom was used by 48% and the pill by 42%. Eight percent of women had never used contraception and 30% were not using a method in the month of conception. Forty three percent had a household income of less than $22,000 and financial barriers were the reason for non use in 32% of those not using a method. Of women who did not use contraception, only 11% used emergency contraception, whereas 78% of those surveyed said they knew about emergency contraception. Sixty-three percent of women said they had received enough contraceptive education to select and use a method effectively. Pacific Island women were least likely to have received adequate contraceptive education or to have been using a method of contraception. CONCLUSIONS: A number of technical problems were identified with condom use. These problems need to be emphasised by sexuality education programmes and contraceptive prescribers. Omitting pills, diarrhoea, vomiting and drug interactions were important causes of pill failure. The seven day rule needs more emphasis when teaching women how to take the pill and when antibiotics are prescribed. Costs were an important barrier to the use of contraception for a significant proportion of women. Section 99 approval should be utilised more readily and the provision of free contraception, especially to low income groups, needs to be urgently explored. PMID- 8196862 TI - Haemophilus influenzae type b disease: prospects for prevention in New Zealand. PMID- 8196863 TI - Coeliac disease: incidence and prevalence in Wellington 1985-92. AB - AIM: A retrospective study was carried out in the greater Wellington area. The objectives of this study were to identify an incidence rate, presenting symptoms and clinical features of coeliac disease. METHODS: Histology archives from the Wellington hospital department of pathology over the last eight years (1985-92) were retrieved and analysed. Abnormal duodenal and jejunal histological sections were reviewed. One hundred and seventy seven biopsy specimens from 127 patients were identified for further study from a total of 367 abnormal duodenal and jejunal biopsy specimens. Diagnosis of coeliac disease was based on information from hospital notes, biopsy request forms, and histology reports. Diagnostic criteria used for coeliac disease were evidence of malabsorption, abnormal histology consistent with coeliac disease and clinical improvement following a gluten free diet. RESULTS: Thirty eight patients were diagnosed with coeliac disease 1985-92 in a population of 267,252. Of these 38 only four were children (0-12 years). Overall incidence was 1.8 per 100,000. The estimated overall prevalence was 70 per 100,000, with 14 per 100,000 for children. The live birth rate was 0.1 per 1000. There was a female predominance of 3:1. Patients presented with a diverse range of problems, most commonly diarrhoea, anaemia, weight loss and steatorrhoea. Three out of the 6 patients who had a single problem had anaemia. CONCLUSIONS: The study has demonstrated an overall incidence and prevalence of coeliac disease in the Wellington region similar to overseas figures. However only 11% of the total were children, which is a very low proportion compared to the 50% reported in Sweden and 25% in Edinburgh. Patients presented with a wide range of clinical features. The threshold for small bowel biopsy should be relatively low in any patient considered to have clinical features of malabsorption. PMID- 8196864 TI - Ethnic differences in diabetes knowledge and education: the South Auckland Diabetes Survey. AB - AIM: To compare the knowledge of diabetes, and diabetes education provision/preferences among European, Maori and Pacific Islands diabetic patients in south Auckland. METHOD: The 331 European, 86 Maori and 123 Pacific Islands patients who were interviewed attended local diabetes services and a stratified subsample of general practitioners. Interviews included closed and open questions of diabetes knowledge, age, sex, diabetes treatment, employment status, weekly household income, school/further education received and the actual and preferred format of diabetes education. RESULTS: Pacific Islands patients knew least, and Europeans most, about diabetes from both open and closed diabetes knowledge questions. The majority of Pacific Islands patients could not name the nature, symptoms or complications of diabetes. This was unaffected by duration of diabetes, place of birth or time in New Zealand, although insulin treated Pacific Islands patients knew more than noninsulin treated patients (closed score 71 SD (4)% vs 61 SD (2)% p < 0.05). Pacific Islands patients were least likely to have received diabetes education (European 69%, Maori 70%, Pacific Islands 49%, p < 0.001). Knowledge scores were higher in those who had received education at diagnosis. Europeans were least likely to want further education (Europeans 52%, Maori 69%, Pacific Islands 63%, p < 0.01). The preferred sources for ongoing education were the lay educator/diabetes nurse specialist service (Europeans 28%, Maori 37%, Pacific Islands 76%), and the hospital based clinic among Europeans (27%) and Maori (36%). No Pacific Islands patients preferred a hospital based ongoing education service, while few diabetic patients of any ethnic group preferred to receive education via their general practitioner. In all ethnic groups, patients wanting more education knew more than those who did not. CONCLUSION: The local delivery of diabetes education is uneven. Among Pacific Islands people, it is grossly inadequate. In order for all patients to receive such education, the diabetes services need to be better coordinated and integrated with primary health care. PMID- 8196865 TI - Chronic paracetamol poisoning in children: a warning to health professionals. PMID- 8196866 TI - Influenza vaccination coverage in old people's homes in central Auckland. PMID- 8196867 TI - Management of epilepsy in childhood. PMID- 8196868 TI - Recertification: a report of a meeting. PMID- 8196869 TI - Mammography screening under 50. PMID- 8196870 TI - Lowering cholesterol. PMID- 8196871 TI - National Maori Diabetes Organisation. PMID- 8196872 TI - Amputations in the surgical budget. PMID- 8196873 TI - Carbamazepine and sertraline. PMID- 8196875 TI - The consumer healthcare reform agenda. American Organization of Nurse Executives. PMID- 8196874 TI - Validity of Maori ethnicity statistics. PMID- 8196876 TI - Nursing informatics core competencies. PMID- 8196877 TI - Malpractice--and the federal employee. PMID- 8196879 TI - Human problems, human beings. PMID- 8196878 TI - Graduate nursing education money and you. PMID- 8196880 TI - Primary nursing: psychological implications. AB - Even with the decreasing lengths of stay, primary nurses and their patients become attached. These issues of "involvement" can be sources of stress and can complicate primary nursing. Recognizing psychological issues leads to greater job satisfaction and professional identity. PMID- 8196881 TI - Innovative behavior in nurse executives. AB - This study addresses the problem-solving styles of hospital nurse executives and explores the relationship between problem-solving style and leader effectiveness. The Kirton Adaption-Innovation Inventory (KAI) and the Leader Effectiveness and Adaptability Description-Self (LEAD-S) were the instruments used to survey nurse executives from 66 medium-sized urban California hospitals. The majority of respondents used innovative approaches, but no correlation was found between problem-solving style and leader effectiveness. PMID- 8196882 TI - Team building: bringing RNs and NAs together. AB - To identify work-related relationships, team building sessions were established with registered nurses and nurse's aides. Within these groups, expectations and philosophies were communicated and resulted in mutual respect and understanding. PMID- 8196883 TI - Power orientation: a study of female nurse and non-nurse managers. AB - Researchers studied the power orientations of female managers as related to career choice, education level, age, and years as a manager. The questionnaire includes six orientations to power: 1) power as good; 2) power as resource dependency; 3) power as instinctive drive; 4) power as political; 5) power as charisma; and 6) power as control and autonomy. Discerning power may explain how one perceives the managerial position. PMID- 8196884 TI - The CLER model: thinking through change. Configurations of social relationships. Linkages to carry communications. Environment(s) inside and around systems. Resources for enabling implementation for incorporating change. AB - The CLER model is presented to nursing professionals as a model for planning and implementing change in interpersonal, institutional and cultural settings. It is useful for generating other models by modeling reality as actually encountered by change agents and adopters. The CLER model is related philosophically to systems thinking (that there is interdependence among social entities), dialectical thinking (that there is mutual shaping among social processes) and constructivist thinking (that human beings take part in creating their own reality). PMID- 8196885 TI - Use of nursing assistants: staff nurse opinions. AB - Use of assistive nursing personnel generates fear, uncertainty and lack of trust in many RNs, yet most agree that "help is needed." The nursing profession must develop minimum standards, a code of ethics and appropriate preparation for nursing assistants. They are here to stay! PMID- 8196886 TI - The heart of patient care. PMID- 8196887 TI - Organizing and documenting clinical standards. AB - The concept of clinical standards of care is not new, but it is one that often is difficult for nurse managers to implement and maintain as part of the daily practice within their Nursing Service. Written clinical standards of Nursing Service were reorganized and streamlined to respond comprehensively to JCAHO, legal, and professional practice requirements and to decreased professional nursing resources. The documentation system developed fulfills medical center requirements and uses non-repetitious, easily understood forms which clearly reflect role differentiation. PMID- 8196888 TI - Using staffing and scheduling information to support change. AB - The growing demand for information about healthcare providers can be met by utilizing the enormous amount of information stored in computerized staffing and scheduling systems. Faster and more accurate staffing, along with optimal use of the available skill mix, enhances both productivity and quality of care. Decreasing overtime and minimizing or eliminating agency care can be far more effective cost savers than direct FTE reduction. Also, data related to staff retention can be invaluable in planning proactive approaches. PMID- 8196889 TI - "Thriving on chaos" works in health services management! AB - A decision-making model developed by two nursing administrators provides quality service using participatory, innovative managerial techniques. Treating the front line service providers as clients proved to be the best way to develop a case management service for the ultimate client--the patient. Encouragement, respect and empowerment led to the formation of regional coalitions under one agency leadership. PMID- 8196890 TI - Shared governance: getting it started. AB - A shared governance model has been developed and implemented in an intensive care unit of a 290-bed community hospital. This resulted from a large staff turnover due to job dissatisfaction stemming largely from lack of autonomy. Scheduling and floating were major factors. Under the unit manager's leadership, four committees of staff nurses designed an appropriate model of participative management. Surveys of 18 and 30 months indicate significant support of the shared governance system, with improved collegiality, enhanced professional growth and a turnover rate of less than 1 percent. PMID- 8196891 TI - Reducing the risk of tuberculosis transmission. AB - Hospital workers are understandably concerned about the risk of acquiring tuberculosis (TB) as they perform their duties, so institutions throughout the United States are developing and implementing procedures to lower the risk of TB transmission in the healthcare setting. The TB infection control plan at University Hospital of Brooklyn is described. PMID- 8196892 TI - Implementing a mass influenza vaccination program. AB - A 15-site health maintenance organization (HMO) implemented a mass influenza vaccination program to heighten awareness of the vaccine and immunize more "at risk" members. Successful interventions conducted over a two-year period included: a direct mail leaflet, pharmacy bag reminders, posters at each medical center, articles in the HMO member newsletter, staff education, standing orders for nursing and, most important, the availability and access to vaccination through walk-in clinics. Immunization rates were examined for patients considered "at-risk." In addition, assessments were made to determine program effectiveness and patient and staff satisfaction. PMID- 8196893 TI - Verbal abuse in nursing: how serious is it? PMID- 8196894 TI - Mentorship: becoming "kindred spirits". PMID- 8196895 TI - Job satisfaction: RNs' status perceptions. PMID- 8196896 TI - Continuous quality improvement in emergency services. PMID- 8196897 TI - Role of cytokines in cancer treatment. PMID- 8196898 TI - Tumor necrosis factor for the treatment of malignancies. AB - Tumor necrosis factor (TNF) is a cytokine produced in vivo by activated macrophages and monocytes with pleiotropic effects on normal and malignant cells. TNF is cytotoxic to several tumor cell lines in vitro and in vivo. Phase I and phase II trials have been conducted to determine toxicity to humans and to evaluate responses. Recent investigations will be reviewed. Despite promising results in vitro and in vivo, data from systemic administration in the treatment of malignancies have been disappointing. Local administration has been successful. Therefore, we suggest that future efforts concerning TNF administration in the treatment of malignancies should aim at local treatment. PMID- 8196899 TI - Interleukin-2: solid-tumor therapy. AB - Interleukin-2 (IL-2) is a soluble factor produced by T cells that stimulates growth and activity of lymphocytes and other immune cells. First noted in murine studies, the antitumor efficacy of IL-2 has been shown to induce partial and complete regression of some tumors in human clinical trials over the past decade. Although the initial clinical success of IL-2 was in combination with lymphokine activated killer cells, IL-2 alone has subsequently been shown to be equally efficacious. Combinations of cytokines and chemotherapies with IL-2 have been generally inconclusive and disappointing with the possible exception of interferon-alpha. Toxicities of IL-2 are common and often dose limiting. Symptomatic therapy has allowed patients to tolerate somewhat higher doses, but has not addressed the underlying mechanisms of these toxicities which may involve mediators such as tumor necrosis factor, interferon-gamma, and nitric oxide. Clinical studies assessing these factors for their involvement in the antitumor effects of IL-2 as well as its toxicities may allow better understanding of IL-2, and perhaps lead to improved cancer therapies. PMID- 8196900 TI - Local interleukin-2 therapy for cancer, and its effector induction mechanisms. AB - This paper reviews the effectiveness of local interleukin-2 (IL-2) therapy and its effector induction mechanisms in vivo. Local therapy with IL-2 and/or lymphokine-activated killer (LAK) cells is associated with far fewer side effects than systemic treatment. Local infusions of IL-2 into malignant pleural effusions and the peritoneal cavity induce LAK cells and secondary production of other cytokines responsible for up- or down-regulation of LAK activity. An understanding of the regulatory mechanism of local LAK induction in vivo may provide the rationale for a more effective therapeutic modality for cancer in humans. PMID- 8196901 TI - Granulocyte-macrophage colony-stimulating factor for cancer treatment. AB - In the 5 years since granulocyte-macrophage colony-stimulating factor (GM-CSF) was first tested clinically, a number of different strategies for its use have been evaluated in patients with malignant disease. These include using GM-CSF to support standard and high-dose chemotherapy, to accelerate myeloid reconstitution following marrow transplantation, to mobilize peripheral blood progenitor cells into the circulation for harvesting and transplantation, and in combination with cycle-specific chemotherapy drugs to enhance their cytotoxicity to leukemic cells. Early results were encouraging and data from randomized studies are now being reported. These are enabling an assessment of the value of these strategies for GM-CSF use in the management of cancer. PMID- 8196902 TI - Macrophage colony-stimulating factor for cancer therapy. AB - Macrophage colony-stimulating factor (M-CSF) is a homodimeric glycoprotein which stimulates differentiation of progenitor cells to mature monocytes and enhances production of hemopoietic growth factors from mature monocytes such as granulocyte-macrophage CSF, granulocyte CSF and megakaryocyte potentiator, suggesting that M-CSF administration enhances production of monocytes, neutrophils and platelets. Since the commercial availability of M-CSF in 1991, serial M-CSF infusions at a daily dose of 8 million units have been performed in patients with acute myeloid leukemia in complete remission after combination chemotherapy. Although M-CSF infusion reduced the duration of neutropenia in 3 of 5 patients, it reduced the duration of pyrexia over 37 degrees C in all patients, and that over 38 degrees C in 4 of 5 patients. Average durations of pyrexia and parenteral antibiotic injections were significantly shorter in M-CSF than in control courses. Although M-CSF infusion reduced the duration of thrombopenia in 2 of 5 patients, it reduced total platelet units transfused in 4 of 5 patients. The average number of platelet units transfused after combination chemotherapy was significantly lower in M-CSF than in control courses. In mice, M-CSF injection increased the serum concentration of reactive nitrogen intermediates which inhibited the growth of L1210 cells, and increased the survival rate of mice previously injected with them. These results indicate that M-CSF may be a promising agent not for improving patients' quality of life after cancer chemotherapy, but also in cancer immunotherapy. PMID- 8196903 TI - Antitumor-promoting activity of mallotojaponin, a major constituent of pericarps of Mallotus japonicus. AB - Mallotojaponin, a major constituent of the pericarps of Mallotus japonicus (Euphorbiaceae), inhibited the action of tumor promoter in vitro and in vivo; it inhibited tumor promoter-enhanced phospholipid metabolism in cultured cells, and also suppressed the promoting effect of 12-O-tetradecanoylphorbol-13-acetate on skin tumor formation in mice initiated with 7,12-dimethylbenz-[a]anthracene. PMID- 8196904 TI - Genotypic, phenotypic and biological characterization of a novel human lung adenocarcinoma cell line (LC 89) AB - A cell line termed LC 89 was established from a peritracheal lymph node metastasis removed from a 54-year-old patient who underwent surgery for pulmonary adenocarcinoma. Chromosomal analyses demonstrated structural and numerical aberrations, with a mode of 54 chromosomes per cell and several nonrandom abnormalities. The localization of intermediate filament antigens, low-molecular weight (LMW) cytokeratins and vimentin, demonstrated a switch from LMW cytokeratins, predominantly expressed in primary tumor cells, to vimentin detected in LC 89 cells that were grown in vitro or transplanted into nude mice. In view of the phenotypic and chromosomal features, LC 89 should provide a useful addition to the cell lines currently available for in vitro and in vivo studies of lung cancer. PMID- 8196905 TI - Predictive value of preoperative carcinoembryonic antigen levels for the prognosis of patients with well-differentiated gastric cancer. A multivariate analysis. AB - Serum carcinoembryonic antigen (CEA) levels were determined preoperatively in 221 patients with well-differentiated gastric cancer. The mean preoperative serum CEA level was 15.9 +/- 88.5 ng/ml (1.0-1,133.0 ng/ml) for all patients, and the incidence of an elevated CEA (> 5 ng/ml) was 11.8% (26/221). The CEA-positive patients had larger tumors, a more prominent serosal invasion, more frequent lymphatic and vascular involvement, less expansive tumor growth and higher rates of lymph node and hepatic metastases than did the CEA-negative patients. Thus, the CEA-positive patients had a more advanced stage of disease, and 61.5% underwent noncurative resection (vs. 11.3% in CEA-negative patients). The survival rate of the CEA-positive patients was lower than that of the CEA negative ones (p < 0.01). As the multivariate analysis revealed the preoperative CEA level to be an independent prognostic factor for survival, an assay for this antigen prior to surgery is to be recommended. PMID- 8196906 TI - Stromal distribution of CA 19-9 as a predictor of lymph node metastases in gallbladder cancer without serosal invasion. AB - Gallbladder cancer without serosal invasion is often diagnosed during the pathologic examination of a gallbladder removed for presumed benign disease. The role of reoperative procedures in these patients is not well established, making it important to define prognostic factors that predict cancer spread. To determine if the pattern of immunohistochemical staining with a monoclonal antibody against CA 19-9 could predict lymph node spread of cancer, 23 patients with gallbladder cancer without serosal invasion were reviewed. CA 19-9 reaction was present in pathology specimens from all 23 patients. Twelve samples (52.2%) showed CA 19-9 in the stroma adjacent to cancer cells, while the remaining 11 did not show any stromal staining against CA 19-9. Lymph node development was found in only 2 (18.2%) of these 11 patients in the nonstromal staining group and 9 (75%) of the 12 patients in the stromal staining group. As these differences were statistically significant, we conclude that immunohistochemical localization of CA 19-9 in gallbladder cancer may be useful in predicting the presence or absence of lymph node involvement, and in developing a rational approach for a reoperative procedure. PMID- 8196907 TI - Usefulness of argyrophilic nucleolar organizer staining for predicting prognosis of patients with recurrent soft tissue sarcoma. AB - Local recurrence of tumor is a common phenomenon in soft tissue sarcoma (STS) and may be accompanied by an increase in malignant potential. In the present study, an increase of proliferative activity in recurrent tumors compared to primary tumors was observed using a silver stain for nucleolar organizer regions (AgNOR), and its implication for predicting prognosis is assessed. 44 patients with STS showing local tumor recurrence were selected. Local recurrence was defined as new tumor growth more than 2 months after the initial surgery in the same region where the primary tumor occurred. All patients received surgery, followed in 11 patients by adjuvant radiotherapy and/or chemotherapy. The histologic subtype was malignant fibrous histiocytoma in 22 cases, synovial sarcoma in 5, leiomyosarcoma in 4, liposarcoma in 3, malignant schwannoma in 3, and others in 7. The interval between initial surgery and local recurrence ranged from 2 to 72 months. No patients changed from one histological subtype to another. Histological changes included an increase in mitosis, cellularity, and sclerosis in 43.2, 31.8, and 27.3%, respectively. The AgNOR count (mean +/- SD) in recurrent tumors (7.22 +/- 2.59) was significantly higher than that in primary tumors (5.58 +/- 2.28; p < 0.0057), clearly showing a tendency for an increase in proliferative activity during recurrence. The 5-year survival rate of patients with a marked increase (> 4) in AgNOR count (16.7%) was worse than with minor to moderate increases (60.0%; p < 0.02). Marked AgNOR increase was more frequently observed in the tumors located in the head and neck and retroperitoneum (40%) than in other sites (9%). Irrespective of the primary site of tumors, a marked AgNOR increase resulted in an unfavorable prognosis. Multivariate analysis of change in histologic factors including AgNOR, cellularity, mitotic counts, pleomorphism, myxoid change, necrosis, sclerosis, and tumor size showed that increase of AgNOR counts was significant (p < 0.05). The present findings suggest that AgNOR counts can be used as a prognostic factor in recurrent STS. PMID- 8196908 TI - Megestrol acetate in advanced breast carcinoma after failure to tamoxifen and/or aminoglutethimide. AB - Seventy-three patients with metastatic breast cancer, whose disease progressed on hormonal therapy with tamoxifen or aminoglutethimide, were treated with megestrol acetate, 160 mg/day. No complete responses were observed. Partial response was achieved in 3 patients (4%), for a median of 9 months (range 5-13). Thirty-five patients (48%) remained stable, for a median of 8 months (3-26). The remaining 35 patients (48%) had clear progression of their metastatic disease on therapy. Response to megestrol acetate was achieved in patients with metastases in bone and pleura only. There was no correlation between response to megestrol acetate and response to prior chemotherapy, prior tamoxifen therapy, previous treatment with aminoglutethimide, or hormone receptor status. The actuarial 24-month survival for all patients was 37%. The main side effects of megestrol acetate included weight gain (20% or over), pruritus, elevation of blood pressure, weakness, and vaginal bleeding; they were only occasionally observed. The objective improvement observed during this trial is disappointing; the only reasons to justify the use of megestrol acetate as second- or third-line hormonal therapy in patients with metastatic breast cancer, would be the relatively long duration of disease stabilization in a large proportion of patients, and the low toxicity observed with the drug. PMID- 8196909 TI - Goserelin in premenopausal advanced breast cancer: clinical and endocrine evaluation of responsive patients. AB - Medical ovariectomy with goserelin is an alternative to surgical oophorectomy. To evaluate the relationship between tumor regression and endocrine changes induced by therapy, 40 premenopausal patients with advanced breast cancer were given 3.6 mg of goserelin subcutaneously fortnightly for the first 4 doses and every 28 days thereafter. We have made a particular analysis of the clinical and endocrine profile of responsive patients. Objective responses were observed in 17 of the 38 evaluable patients (45%), 6 cases achieving complete remission. Serum estradiol was suppressed in castrated women, although there was a tendency towards an increase in serum follicle-stimulating hormone over time. No statistically significant difference was observed in the hormonal profiles of patients experiencing a complete or partial response. Our experience confirms that goserelin is as effective as oophorectomy and that there is a clear correspondence between clinical response and drug-induced estrogen suppression. PMID- 8196910 TI - Primary gastric non-Hodgkin's lymphoma localized to the gastric wall: no adjuvant treatment following radical surgery. AB - The paper presents the experience with watch-and-wait policy following radical surgery in 25 patients with primary gastric non-Hodgkin's (NH) lymphoma localized to the gastric wall. The median follow-up is at the moment 40 months (range 18 85). Only 3/25 patients have relapsed (during the first year of the follow-up) and achieved a complete response following chemotherapy. The median disease-free interval following surgery is at the moment 40+ months, and the median survival 40+ months. Primary gastric NH lymphoma localized to the gastric wall, regardless of the histological grade, probably does not need any adjuvant treatment following radical surgery. In occasional patients with lymphoma relapse, the disease can be controlled by additional chemotherapy. PMID- 8196911 TI - Treatment of metastatic colorectal cancer patients with 5-fluorouracil in combination with recombinant subcutaneous human interleukin-2 and alpha interferon. AB - We treated 14 patients with progressive metastatic colorectal cancer, using a combination of subcutaneous recombinant human interleukin-2 (4.8 x 10(6) IU/m2 three times daily on days 1 and 22, and twice daily on days 2 and 23, followed by 2.4 x 10(6) IU/m2 twice daily on days 3-5, 8-12, 24-26, and on 5 consecutive days per week, starting day 29), recombinant human interferon-alpha 2a (5.0 x 10(6) U/m2 thrice weekly), and 5-fluorouracil (750 mg/m2 i.v. bolus on days 15-19, and at weekly intervals thereafter, with a 1-week off-therapy interval every 4 weeks). Therapy was continued until disease progression occurred. Four (29%) and 8 (57%) evaluable patients achieved partial remission and stable disease, respectively; median response duration was 5.9 months. Toxicity of this regimen was moderate; the most common side effects were thrombocytopenia, leukopenia, nausea/vomiting, anorexia, malaise and fevers in all patients, along with diarrhea (63%) and mucositis (54%). Less than 10% of patients developed WHO grade IV toxicity; no toxic deaths occurred. Efficacy of this combination was not substantially different from alternative 5-fluorouracil-based regimens. PMID- 8196912 TI - A comparative study on effects of doxorubicin alone or mixed with lipiodol given through the hepatic artery or portal vein for liver tumors in rats. AB - Vascular feeding of metastatic liver tumors at early stage is uncertain. It is controversial whether anticancer agents should be given through the hepatic artery or portal vein. In order to clarify this point, a rat model of liver metastases generated by an intraportal injection of syngeneic tumor cells was used to determine the optimal regional chemotherapeutic modality for early hepatic metastases. The rats given the tumor cells through the portal vein were placed into 5 groups: In groups I and II, Adriamycin (ADR) 4 mg/kg alone was given either into the hepatic artery or into the portal vein, respectively, 24 h after the inoculation of tumor cells. In groups III and IV, ADR mixed with lipiodol (lipiodolized ADR) 4 mg/kg was given into the hepatic artery or into the portal vein, respectively, 24 h after inoculation. For the group V rats, no treatment was given after inoculation of the tumor. When a comparison was made with regard to the forms of anticancer drug administered, statistically significant differences in survival rates were recognized between groups I and III (p < 0.001), and groups II and IV (p < 0.05). The anticancer agent not mixed with lipiodol and given through the hepatic artery had a more preventive effect than that given through the portal vein. Thus, we conclude that administration of ADR not mixed with lipiodol and given through the hepatic artery is the preferred modality for treating early metastatic liver tumors. PMID- 8196913 TI - The mechanism of recurrence of mouse myeloid leukaemia after total body irradiation and bone marrow transplantation. AB - RFM mice were X-irradiated (9.5 Gy) 3, 4, 5, 6 or 7 days after inoculation of a transplantable strain-specific myeloid leukaemia (ML) and were reconstituted or not with syngeneic or allogeneic bone marrow cells. Recurrent leukaemia was observed in mice with either type of the bone marrow transplant, indicating that ML cells survived the dose of 9.5 Gy of X-rays. ML cells exposed in vitro to high doses of X-rays (20, 30, 40, 50, 60 Gy) and injected into lethally irradiated syngeneic recipients were still capable of forming leukaemic colonies on the spleens. Higher doses (70, 80, 90 and 100 Gy) abolished the colony formation completely. Irradiated ML cells were also capable of causing leukaemia (hepatosplenomegaly) if inoculated into lethally irradiated CBA mice reconstituted with bone marrow cells of CBA or RFM mice. That was attributed to the release of a leukaemogenic factor from the ML cells, capable of transforming transplanted normal cells. PMID- 8196914 TI - Effects of weak alternating magnetic fields on nocturnal melatonin production and mammary carcinogenesis in rats. AB - Since extremely low frequency (i.e., 50- or 60-Hz) magnetic fields (MFs) from overhead power lines and other electromagnetic sources are ubiquitous in modern societies, the possible carcinogenic effect of such fields recently suggested by epidemiological studies has engendered much concern. However, in view of various unknown and uncontrolled variables which may bias epidemiological studies on MF interactions, a causal relationship between MFs and tumorigenesis can only be determined precisely in animal experiments. The goal of the study reported here was to determine if low frequency MFs at the low flux densities which are relevant for human populations induce tumor-promoting or copromoting effects in a model of breast cancer. Furthermore, since reduction in pineal production of melatonin has been implicated as a cause of tumor promotion by electromagnetic fields, determinations of nocturnal melatonin peak levels in serum were performed during MF exposure. Mammary tumors were induced by intragastric administration of 20 mg (5 mg/week) 7,12-dimethylbenz(a)anthracene (DMBA) in female Sprague-Dawley rats. Groups of 36 rats were either sham-exposed or exposed for 91 days at a 50 Hz gradient MF of 0.3-1 microT, which is a relevant range for elevated domestic MF exposure as arising from neighboring power lines. Nocturnal melatonin levels were significantly reduced by exposure to this weak alternating MF. However, histopathological evaluation of mammary lesions did not disclose any significant difference between MF- and sham-exposed animals. Incidence of mammary tumors was 61% in controls versus 67% in MF-exposed rats. The predominant tumor type was the invasive adenocarcinoma, which was found in 21 rats of both groups. Examination of tumor size did not indicate significant differences in tumor burden between both groups. Furthermore, the incidence of preneoplastic lesions was not altered by MF exposure. Thus, the data of this study indicate that alternating MF do not exert significant tumor promoting or copromoting effects at environmentally relevant flux densities in the rat mammary cancer system. PMID- 8196916 TI - A comparison of two semi-quantitative surgical keratometers: the modified Hyde ruler and the Barrett keratoscope with "astigmatic dial". AB - The Hyde astigmatic ruler is an inexpensive, semiquantitative, hand-held, surgical keratometer that we modified by geometrically calculating the correct shape of its ellipses. The Barrett keratoscope is a cheap, disposable, qualitative keratometer that, unlike the Hyde ruler, produces a bright corneal image. We designed a transparent overlay, or "astigmatic dial," to use with the keratoscope. This overlay determines the magnitude of astigmatism and sets the distance the keratoscope is held from the cornea by direct comparison with the corneal image. Using a model cornea, we compared our modified Hyde ruler with the Barrett keratoscope and astigmatic dial to determine the accuracy of measurement provided by each. Both instruments had good predictive values for the true astigmatism; however, the Barrett keratoscope/astigmatic dial provided more consistent measurements of the astigmatism. We believe the keratoscope and dial provide a cheap, convenient, and accurate alternative to the more expensive microscope-mounted keratometers. PMID- 8196915 TI - Immunochemotherapy in B-16-melanoma-cell-transplanted mice with combinations of interleukin-2, cyclophosphamide, and PSK. AB - The effect of combination immunochemotherapy using interleukin-2 (IL-2), PSK and cyclophosphamide (CY) was evaluated in a pulmonary metastasis model in BDF1 mice. B-16 melanoma cells were inoculated into a hind limb. On day 3 after inoculation, 20 mg/kg of CY was administered intraperitoneally, and IL-2 (3.75 x 10(4) BRM units/head) was injected into the tail vein on days 7, 8 and 9. PSK (1,000 mg/kg) was administered orally every day from day 1 to day 10 using a stomach tube. This treatment cycle was repeated three times. Using this combination therapy, the cytotoxicity of lymphokine-activated killer cells and tumor-infiltrating lymphocytes was enhanced. Pulmonary metastasis was remarkably suppressed and a prolongation of survival was obtained compared with the nontreated group and an IL-2+CY group. The effect was augmented by repeating the therapy protocol. By analyzing the killer activity and surface markers of tumor-infiltrating lymphocytes, it was recognized that increased numbers of Lyt-2-positive T cells with augmented cytotoxicity were obtained. This treatment modality should have clinical significance. PMID- 8196917 TI - Clinical utility of the Barrett keratoscope with astigmatic dial. AB - Intraoperative keratometry allows some degree of control over corneal astigmatism during cataract surgery. I describe the clinical use of the Barrett keratoscope combined with an astigmatic dial that quantifies the information obtained by this simple, inexpensive, hand-held surgical keratometer. Based on a comparison of intraoperative measurements with those taken after extracapsular cataract surgery with an automated keratometer, I conclude that intraoperative keratometry reliably predicted the postoperative astigmatism. For those who had the intraocular pressure (IOP) set between 15 and 20 mm Hg intraoperatively, the mean deviation of the first postoperative measurement from the intraoperative measurement of astigmatism was +/- 1.03 D (standard error, 1.56 diopters; 95% confidence interval 0.712 to 1.35 D). When the IOP was not set, the postoperative astigmatism differed from the intraoperative reading by more than 2.00 D for 50% of the cases. Setting the IOP prior to intraoperative keratometry significantly improved the reliability of the measurement. Intraoperative keratometry by the simple device used in this study is of sufficient utility to allow the surgeon to adjust for the predicted changes in the corneal astigmatism at the time of surgery. PMID- 8196918 TI - Persistent Torulopsis magnoliae endophthalmitis following cataract extraction. AB - Postoperative fungal endophthalmitis typically manifests as an indolent uveitis, weeks to months after surgery. In our patient, Torulopsis magnoliae endophthalmitis appeared as an acute, purulent postoperative endophthalmitis on the third day following extracapsular cataract extraction with implantation of a posterior chamber intraocular lens (IOL). The patient required three separate vitrectomy operations with instillation of intravitreal Amphotericin B; the last operation also included complete removal of the posterior capsule and IOL. This case, which is to our knowledge the first reported case of T. magnoliae endophthalmitis, is unusual in that it manifested as an acute, fulminant infection in the early postoperative period and was recalcitrant to standard endophthalmitis therapy. PMID- 8196919 TI - Surgical wound defects associated with endophthalmitis. AB - Twenty-five consecutive cases of culture-proven postsurgical endophthalmitis were evaluated. Patients underwent wound revision and pars plana vitrectomy with intravitreal antibiotic and steroid infusion (gentamicin 8 micrograms/cc, clindamycin 9 micrograms/cc, dexamethasone 8 micrograms/cc) and injection (gentamicin 100 micrograms plus clindamycin 200 micrograms [and amphotericin 5 micrograms in one case] and dexamethasone 800 to 1000 micrograms). Twenty cases demonstrated wound defects (eg, wound gape/malapposition, abscess/tissue necrosis, suture dehiscence, leak, vitreous wick). Culture-proven isolates included both gram negative and positive bacteria and fungi. Visual acuity improved in 18 of the 20 (90%) gram positive cases. Ten of the 17 (59%) patients in the Staphylococcus epidermidis subgroup achieved a visual acuity of 20/50 or better. Surgical wound defects are frequently associated with culture-proven endophthalmitis. When vitrectomy is included as part of the treatment regimen, we recommend meticulous inspection and closure of any defective surgical wounds associated with endophalmitis. PMID- 8196920 TI - Lid crease and capsulopalpebral fascia repair in congenital entropion and epiblepharon. AB - Forty-one eyelids of 21 patients with congenital entropion or epiblepharon underwent transcutaneous reconstruction of the eyelid crease and retractor (capsulopalpebral fascia). All of the patients demonstrated lack of cutaneous capsulopalpebral fascia attachment. In contrast with the patients with epiblepharon, those with congenital entropion also had partial or complete absence of tarsal-capsulopalpebral fascia attachment. Surgical treatment included anastomosis of the capsulopalpebral fascia, tarsal border, and eyelid skin crease; no skin or muscle was removed. With a minimum follow up of 1 year, malposition recurred in 3 of the 33 (9%) eyelids with epiblepharon, and in none of the 8 eyelids with entropion. PMID- 8196921 TI - Vitreoretinal toxicity of acetazolamide following intravitreal administration in the rabbit eye. AB - Acetazolamide, a carbonic anhydrase inhibitor, has been shown effective in the treatment of cystoid macular edema; however, chronic use of the drug is limited by its serious systemic side effects. Intraocular administration can eliminate these systemic complications. We evaluated vitreoretinal toxicity after intravitreal injection of acetazolamide in the rabbit eye. The right eye of each rabbit received a single acetzolamide injection; the left eye received balanced salt solution and served as a control. The effect of the drug was evaluated by clinical observation, electroretinography, and histopathologic study. Intravitreal injection of up to 0.5 mg acetazolamide did not cause vitreoretinal toxicity. Injection of 1 mg or higher doses depressed the b-wave amplitude of electroretinograms and damaged the outer segments of the photoreceptors, as determined by light and electron microscopy. PMID- 8196922 TI - The role of fibroblast inhibitors on corneal healing following photorefractive keratectomy with 193-nanometer excimer laser in rabbits. AB - Corneal stromal haze has been seen following photorefractive keratectomy with the 193-nanometer excimer laser. Topical antimetabolites aimed at decreasing the haze have been investigated in the rabbit model. We used the VISX 193-nanometer excimer laser to create 6.0-millimeter, -5.00-diopter ablations in 10 Dutch rabbits. Each rabbit was randomized to treatment groups using topical prednisolone acetate, 5-fluorouracil, heparin, prednisolone and heparin, or prednisolone and 5-fluorouracil. Topical agents were instilled twice daily for 2 weeks. Corneal stromal haze developed in all of the eyes. At 2 weeks, there was a significant difference between the degree of haze in the treated eyes and in the untreated controls (P = .02). At 6 weeks, no significant difference remained (P = .07). There were no significant differences in corneal haze among the treatment groups. Thus, all treatments reduced haze at 2 weeks, but the effect was transient, with controls clearing to an equivalent haze by 6 weeks. We conclude that the agents investigated in this rabbit model provided only a transient benefit in reducing corneal haze following excimer laser photoablation. PMID- 8196923 TI - Penetrating ocular trauma in children by "broomstick bows and arrows". AB - Ocular trauma by "broomstick bows and arrows" is a unique penetrating injury among Indian children. Hitting the eye with a great velocity, these highly contaminated missiles may cause severe damage. The results of surgical treatment of 100 children who suffered such trauma are presented. Anatomic success, ie, successful reconstruction of the globe with attached retina, was attained in 85 (85%) of these eyes. Functional success, ie, improvement in visual acuity of two Snellen lines in eyes with measurable preoperative acuity, or improvement to at least 2/60 in the eyes with preoperative acuities of light perception or hand movements, was attained in 62 (62%) of the eyes. Of the functionally successful eyes, an acuity of 6/9 or better was achieved in 28 (45.2%). Factors predictive of poor anatomical success were: injuries involving both anterior and posterior segment (P < .02), endophthalmitis (P < .05), and presence of retinal detachment with or without proliferative vitreoretinopathy (P < .05). Mean follow up was 4.5 +/- 3.59 months (range, 2 to 24 months). PMID- 8196924 TI - Black-diaphragm intraocular lens for correction of aniridia. AB - In cooperation with Morcher GmbH, we developed a black-diaphragm aphakia intraocular lens (IOL) designed to correct congenital and traumatic aniridia. Since June 1991, we have implanted this IOL into five eyes with congenital aniridia combined with cataract, and into eight eyes with traumatic aniridia combined with cataract or aphakia. Positioning the IOL was rather difficult, especially in the traumatic cases with inadequate capsular support, and in combination with penetrating keratoplasty. After up to 15 months' follow up, functional results are encouraging. However, slight persistent intraocular inflammation was observed in all of the eyes, more obviously in the traumatic cases. The effect of the IOL on the corneal endothelium is still being investigated. Cystoid macular edema was observed in one eye, but probably preexisted in this eye, following several earlier surgical procedures. Glaucoma was observed preoperatively in five eyes; postoperatively, in six. After surgery, it was controlled medically in 4 eyes, surgically in 1, and remained uncontrolled in 1. PMID- 8196925 TI - Control of eyelid retraction associated with Graves' disease with botulinum A toxin. AB - Two patients had satisfactory control of eyelid retraction associated with thyroid orbitopathy with repeated treatment of the levator palpebrae superioris muscle with botulinum A toxin. The effects of the toxin lasted for 3 to 4 months. PMID- 8196926 TI - Hyperplastic pupillary membrane and laser therapy. AB - The eyes in two cases of extensive hyperplastic pupillary membranes with significant reduction of visual acuity and clarity were subjected to sectioning of the membranes in the superior 270 degrees of the pupil using a Q-switched Nd:YAG laser. The complications of microhemorrhages, pigment dispersal, and elevation of intraocular pressure were insignificant, while the objective and subjective improvement in vision was remarkable. PMID- 8196927 TI - The corneal quilt: a protective device designed to reduce intraoperative retinal phototoxicity. AB - The corneal quilt is a simple, safe, inexpensive, and effective device designed to decrease the risk of intraoperative retinal phototoxicity from the operating microscope. Retinal injury is a well documented hazard, especially during prolonged procedures. The corneal quilt can be easily used as an adjunct to other methods designed to protect the retina from excessive incident light. In this study, we fashioned an approximately 6- x 5-millimeter semi-transparent corneal occluder from the nonadhesive portion of a 3M Steridrape. We determined spectrophotometrically that the corneal quilt reduced the transmission not only of visible light, but of ultraviolet and blue wavelengths as well, the wavelengths known to be the most phototoxic to the retina. However, no data were obtained actually demonstrating the degree to which light is scattered after transmission through the corneal quilt. PMID- 8196928 TI - Peters' anomaly. PMID- 8196929 TI - 5-Fluorouracil vs single-plate molteno implantation. PMID- 8196930 TI - Surgery for upper eyelid retraction. PMID- 8196931 TI - Determination of the content of water in bovine corneas by differential scanning calorimetry and thermogravimetric analysis. AB - The 'bound', 'bulk', and total water contents in bovine corneas were investigated using differential scanning calorimetry and thermogravimetric analysis. The amount of total water (expressed as a function of total wet mass) was observed to be 83.7 +/- 1.1% using lyophilization and 84.1 +/- 0.8% using thermogravimetric analysis. These values are not significantly different from one another, but some discrepancies are observed when these values are compared with the values reported in the literature, thus indicating a need for guidelines concerning sample handling and analysis of these tissues. The 'bound' water was observed to be 62.3 +/- 2.7 (% of total water) and the amount of 'bulk' water was calculated to be 20.8 +/- 2.5 (% of total water). PMID- 8196932 TI - Intravitreal use of foscarnet: retinotoxicity of repeated injections in the rabbit eye. AB - Cytomegalovirus retinitis is the most frequent ocular opportunistic infection in AIDS patients. In selected cases intravitreal injections of foscarnet may be the sole therapeutic possibility. The retinal toxicity of the drug, however, has not yet been thoroughly investigated. Our present study in the rabbit eye concerns the retinal toxicity of 2, 4, and 6 intravitreal injections of 3.6 mg of foscarnet, using ophthalmoscopy, histology and electrophysiology to evaluate retinal damage. The results show that foscarnet may be employed intravitreally without substantial damage to the retina, but only in short courses of injections when no other therapeutic possibility may be utilized. PMID- 8196933 TI - Effect of some phytogenic agents and synthetic compounds on complement cascade mediated hemolysis. AB - A variety of anti-inflammatory compounds obtained from various medicinal plants (phytogenic) as well as some synthetic compounds were tested on the complement cascade in vitro. Bovine erythrocytes were treated with rabbit antibovine red blood cell antibody. Rabbit plasma was diluted with veronal buffer and mixed with erythrocytes in the presence or absence of drugs and incubated. Erythrocytes were pelleted and the absorbance of the supernatant at 412 nm determined. Drugs could be grouped into three categories; (a) those with no effect whatsoever; (b) those which produced definite enhancement of the release of hemoglobin by the complement cascade, and (c) prednisolone, which inhibited the release of hemoglobin by the complement cascade. We suggest that prednisolone and the drugs which had no effect on the complement cascade are safer to use as anti inflammatory agents, while drugs enhancing the complement cascade may have potential adverse properties. PMID- 8196934 TI - Toxic effects of systemic retinoids on meibomian glands. AB - Systemic use of retinoids is common in the treatment of various dermatological disorders. Blepharitis and conjunctivitis have been reported in 20-45% of the patients following systemic treatment with 13-cis-retinoic acid. Our purpose was to study the histopathological changes in the eyelids caused by long-term systemic treatment of female New Zealand rabbits with isotretinoin (2 mg/kg) and etretinate (2 mg/kg). The histopathological evaluation showed degenerative changes in the meibomian gland acini, leading to cell necrosis and a decrease in the basaloid cells lining the acini walls. No evidence of acute or chronic inflammatory reaction was noted. PMID- 8196935 TI - Mechanism of intraocular pressure decrease after contact transscleral continuous wave Nd:YAG laser cyclophotocoagulation. AB - Twenty-two eyes of 11 cynomolgus monkeys were subjected to contact transscleral cyclophotocoagulation with a continuous-wave Nd:YAG laser. The right eye of each monkey was coagulated at the pars plicata region by the contact probe placed 1.0 mm from the limbus, while the left eye of each monkey was coagulated at the pars plana region by the contact probe placed 3.0 mm from the limbus. Physiological and morphological studies were carried out up to 6 months after the treatment. The postoperative intraocular pressure showed a significant decrease within 1 week, corresponding to the inflammation of the anterior chamber. A gradual increase of the intraocular pressure occurred from the 2nd week on and returned to the preoperative value 8 weeks after pars plicata coagulation. The pars plana coagulation group maintained the intraocular pressure lower than the preoperative value until the end of the observation period. Histopathological examinations were carried out by the use of tracer particle perfusion into the anterior chamber. The pathologic features of pars plicata coagulation were necrosis, followed by atrophy of the ciliary process. The tracer particles accumulated at the anterior portion of the space between the bundles of ciliary muscle. The pathologic features of pars plana coagulation were necrosis followed by extension of proliferative tissue into the vitreous. The surrounding extracellular space of the stroma was enlarged, and the ciliary muscles were separated from the sclera. The tracer particles accumulated at the enlarged extracellular space of the stroma and the opened suprachoroidal space. These results suggest that the decrease of the intraocular pressure after pars plicata cyclocoagulation resulted from the reduction of aqueous secretion, whereas that after pars plana cyclocoagulation resulted from enhancement of the uveoscleral outflow through the enlarged extracellular space from the anterior chamber into the suprachoroidal space. PMID- 8196936 TI - Effect of in vivo application of the ginkgo biloba extract EGb 761 (Rokan) on the susceptibility of mammalian retinal cells to proteolytic enzymes. AB - Lesions, inflammations, or degenerative insults of the human retina are accompanied by the release of proteolytic enzymes. Their deleterious effect may be enhanced by the release of free radicals. Ginkgo biloba extracts are known to exert protective influences against the action of free radicals, and this prompted us to ask whether the application of such extracts might protect retinal tissue against proteolytic damage. Eighteen adult rabbits were fed for 3 weeks (+/- 3 days) with 40 mg/kg of G. biloba extract (EGb 761) or a terpene-free fraction of this extract, dissolved in their drinking water. Twelve control rabbits received no G. biloba extract. The animals were then euthanatized and their retinae isolated. After appropriate enzymatic treatment, the tissue was dissociated and the number of isolated Muller cells counted as an indication of the strength of the proteolytic effects. There was a significant protective action of EGb 761: in an average control rabbit 5,200 cells per milligram retinal tissue were isolated; application of EGb 761 markedly reduced this number to 2,500 (terpene-free fraction; CP 205) or 3,050 (terpene-containing fraction). It is concluded that G. biloba extracts may have a significant therapeutic value in cases of retinal damage. PMID- 8196937 TI - Topical treatment of experimental acute corneal inflammation by dexamethasone and nonsteroidal drugs. AB - In this study, we have correlated the relative effectiveness of nonsteroidal anti inflammatory drugs versus corticosteroids in the topical treatment of acute corneal inflammation. The authors have studied the effect of 1 drop every 6 h of flurbiprofen 0.03%, indomethacin 1%, diclofenac 0.1% and dexamethasone 0.1% in an experimental model of corneal alkali burn. The objective parameters used to evaluate the corneal inflammatory response were Luminol-enhanced chemiluminescence, ultrasonic pachymetry and computer-assisted analysis of the area of the corneal ulceration. Indomethacin 1% showed statistically significant effects on the improvement of all the parameters tested in the study. No such effect was demonstrated for flurbiprofen 0.03% or diclofenac 0.1%. We can conclude that indomethacin 1% is an effective drug in the treatment of experimental acute corneal alkali-burn inflammation. PMID- 8196938 TI - Effect of genetically determined host factors on the efficacy of vidarabine, acyclovir and 5-trifluorothymidine in herpes simplex virus type 1 infection. AB - The susceptibility of Herpes simplex virus (HSV) to acyclovir (ACV), 5 trifluorothymidine (TFT) and vidarabine (Ara-A) in HSV-infected embryo fibroblasts from BALB/c and C57BL/6 mice as well as Vero cells were measured. Ara A and TFT (at its highest concentration) were more effective in Vero cells and BALB/c mouse embryo fibroblasts (MEF) than in C57BL/6 MEF. In contrast, ACV was more effective in C57BL/6 MEF than BALB/c MEF and Vero cells. These data suggest that genetically determined differences in the ability of host cells to support the replication of HSV influence the activity of antiviral drugs. PMID- 8196939 TI - Review of embryology and its relation to ocular disease in the pediatric population. AB - This overview of normal ocular development concentrates on those areas that more commonly undergo maldevelopment, some of which are discussed in more detail in other papers in this Symposium. Many of the congenital anomalies routinely seen in children are reviewed and the possible mechanisms leading to these anomalies are discussed. PMID- 8196940 TI - Genetics review: relation to ocular disease. AB - This study is a review of modes of transmission of genetic traits, how they relate to ocular diseases, and abnormalities frequently seen by primary eye care practitioners. Traits showing autosomal dominant (AD), autosomal recessive (AR), X-linked (XR) recessive, chromosomal aberrations, and multifactorial (M) inheritance are listed. General guidelines for genetic counseling are given. PMID- 8196941 TI - Pediatric cataracts--diagnosis and treatment. AB - This paper discusses the causes and treatment of congenital and acquired cataracts in children. Although congenital cataracts are relatively uncommon, they are one of the leading causes of serious visual impairment in neonates. Successful visual rehabilitation of these patients is predicted on prompt diagnosis and surgical and optical intervention. The issue of deprivation amblyopia and the critical period of visual development are integral to their effective treatment. Acquired cataracts are more common than congenital cataracts. They are usually easier to treat because vision developed before the formation of the cataract and deprivation amblyopia is not present. The treatment of pediatric cataracts is made more complicated than cataracts in adults because of the growth and development of the eye and the inevitable necessity of treating amblyopia. PMID- 8196942 TI - Congenital optic nerve hypoplasia. AB - Congenital optic nerve hypoplasia (CONH) is an increasingly recognized cause of low vision in children. The spectrum of ophthalmoscopic and clinical presentations of CONH is described here with illustrative cases. Some children with unilateral CONH develop a secondary, functional amblyopia that may respond to patching during visual development. Children with bilateral CONH, poor vision and nystagmus usually present early and have a high risk of exhibiting central nervous system (CNS) malformations and treatable endocrine deficiencies. PMID- 8196943 TI - Lacrimal system abnormalities. AB - This report outlines several of the more important abnormalities of the lacrimal system in infants and young children. Although rare, alacrima can be a very difficult clinical problem to treat. The most common cause of alacrima is the Riley-Day syndrome. Nasolacrimal duct obstruction is a very common anomaly in children. The clinical appearance and treatment of this disorder are discussed. PMID- 8196944 TI - Ocular findings in abused children and infants born to drug abusing mothers. AB - The ocular findings in physically abused children and children born to mothers who abuse drugs are discussed. Some of the ocular and systemic findings and long term effects of drug abuse on the infant are unknown, and only time will characterize them. This article summarizes current information and provides information to assist detection of child abuse. PMID- 8196945 TI - A method for correction of CA/C ratio based on linear model of accommodation and vergence. AB - Measurement of the response CA/C ratio has required that the target used to stimulate the vergence system provides no blur information to the accommodative system. Although several methods have been proposed to open the accommodative feedback loop, it is difficult to ensure that a vergence target produces no stimulus for accommodation. To avoid this problem, we have derived a formula based on a linear model of the accommodative and vergence systems that allows the CA/C ratio to be estimated when the accommodative loop is not opened completely. An experiment was conducted to verify the derived formula. Two targets, Snellen letters and a small point source, were used to provide different blur-inputs to the accommodative system. CA/C ratios were estimated from the formula using measures of accommodation and vergence obtained with these two targets for eight subjects and showed a high correlation. The formula, therefore, was shown to provide a consistent estimate of the CA/C even when the accommodative loop was not opened completely. PMID- 8196946 TI - Outcome of low vision aid provision: the effectiveness of a low vision clinic. AB - PURPOSE: Although there is an increasing need for primary low vision (LV) care, few studies have considered the success rates of optometric LV rehabilitation. We considered the objective success and perceived benefit obtained by 57 elderly LV patients. METHOD: Tests of reading speed and questionnaires were administered in the patient's home after initial and follow-up visits to a LV clinic. Additional information was taken from the patient's clinic record. RESULTS: Benefits from attending the clinic were reported by 89.5% of patients and 81% of patients were regularly using low vision aids (LVA's). There was a discrepancy between ability to read 1M print in the clinic (75% of patients) and the reported ability to read regular-sized print at home (35%). Perceived benefit from visiting the clinic was strongly associated with the ability to perform daily living tasks and to read 2M print. There was some association between perceived benefit and frequency of using the LVA's, but not with duration of use. CONCLUSION: The results encourage a change in emphasis during LV assessments from sustained reading to the ability to perform daily living activities. PMID- 8196947 TI - Ocular pulse and pulsatile change of scleral strain in living in situ rabbit eyes. AB - We investigated ocular pulse (OP), pulsatile change of scleral strain (PSS), and intraocular pressure (IOP) to evaluate extensibility of the sclera in seven living rabbit eyes. OP and IOP were measured by a semiconductor pressure transducer and PSS was measured using a small foil strain gauge. Both OP and PSS generated similar bell-shaped curves in relation to IOP. Between OP and PSS, there was a linear relation, the gradient of which was considered to be an index of the modulus of elasticity of the sclera. With further refinement of the method, it is possible to apply this technique to human eyes. PMID- 8196948 TI - Systemic medication use and health status in the older adult population. AB - Elderly adults have more ocular and systemic disorders than younger adults; there is a corresponding rise in the number of medications used by older adults. Additional medication usage contributes to an increase in the number of adverse drug reactions and also interferes with the efficacy of medications. In this self report study, the number and types of medications used by older adults (N = 50) vs. middle-aged adults (N = 20) and the systemic health status of these two groups are assessed. Significant differences were determined between the two age groups for drug usage (p = 0.0964, Fisher's exact test), for specific drug categories, the total number of reported health and ocular disorders (p = 0.0001, t-test), and the types of health disorders. These results emphasize the importance of accurate case histories in determining ocular and systemic health conditions and their associated treatment and in the detection of inappropriate drug usage. PMID- 8196949 TI - Evaluation of the performance of spectacle lens "transmittance meters". AB - PURPOSE: Inexpensive transmittance meters have recently been developed for measuring of mean ultraviolet (UV) radiant transmittance and luminous transmittance of spectacle lenses. Our purpose was to determine how accurately these meters measured transmittance. METHODS: The mean UV transmittance and the luminous transmittance of a series of lenses were determined using a spectrophotometer. Transmittance meters were then used to measure the same lenses. RESULTS: In general, the meters overestimated total (mean) UV transmittance. Luminous transmittance was relatively accurately measured by those meters which had this capability. CONCLUSIONS: Although the meters do not measure UV transmittance accurately, they are still useful for determining if a lens transmits any UV radiation. The relatively narrow response range of the meters, centered at 360 to 380 nm, is responsible for the measurement error of mean UV transmittance. PMID- 8196950 TI - Apparent image quality of magnifiers depends on amplitude of accommodation. AB - We investigated the importance of the role of amplitude of accommodation in assessing the usefulness of magnifiers. Accommodation must be exerted to scan across the image produced by a magnifier that exhibits astigmatism and curvature of field. In general, increasing amounts of negative accommodation are required to scan from the center to the edge of the image field of view (FOV) when a simple magnifier is set for nominal magnification. It is necessary to refocus the magnifier (move it closer to the object plane) to convert the demand to positive accomodation. We used the OSLO program to design and evaluate the oblique astigmatism of four common types of magnifiers: Equiconvex, Best-form, Aspheric, and the Steinheil triplet, in powers of 10, 20, 40, 60, and 80 D. We found that the circle of least confusion (CLC), produced by the Equiconvex and Best-form lenses set at nominal magnification, lie on a surface that demands as much as 2.75 D of negative accommodation to view the CLC at the edge of a 30 degrees FOV. By refocusing the magnifier, the CLC at the edge of the field can be imaged at infinity, i.e., have zero vergence, and the demand for negative accommodation may be eliminated, but then about 2.4 D of positive accommodation is required to scan to the center of the field. The Aspheric and Steinheil magnifiers largely corrected the astigmatic errors and flattened the field. Less than 0.75 D of accommodation was sufficient to scan from the edge to the center of the object. Depending on the degree of uncorrected astigmatism and field curvature, presbyopic patients, lacking accommodative ability, will perceive constricted in focus zones in the image field. They will continuously have to refocus the magnifier to bring adjacent zones into best-focus. This condition may cause a presbyope to reject a magnifier thought to be of good quality by a young clinician who can accommodate for best-focus across the entire FOV. PMID- 8196951 TI - ["...how should nursing work?"]. PMID- 8196952 TI - [Nursing research between requirement and reality]. PMID- 8196953 TI - [Development of a day care center. Case study on the process of the development of a special facility for the elderly]. PMID- 8196954 TI - [Young adults are doing research: a project from the nursing school of the Rudolfinerhaus in Vienna]. PMID- 8196955 TI - [Friederike Pichler: "Nursing as an individual service". Interview by Harald Verworner]. PMID- 8196956 TI - [Home care services in Lower Austria--the situation. Karin Tupy has developed- against some opposition--a private home nursing service]. PMID- 8196957 TI - [Home care services in Vorarlberg: the Austrian Nursing Association as a center for their coordination]. PMID- 8196958 TI - [Guidelines in nursing]. PMID- 8196959 TI - [Hygiene guidelines in home nursing]. PMID- 8196960 TI - [Individual patient care]. PMID- 8196961 TI - [In the hospital the patient is deprived of his rights]. PMID- 8196962 TI - [Is the nurse suited to her work? Many questions are demanding answers]. PMID- 8196963 TI - Dislocation and fracture-dislocation of the carpometacarpal joints. AB - Dislocations and fracture-dislocations of the carpometacarpal joints are rare. Diagnosis requires a high index of suspicion, careful examination, and appropriate radiography. Treatment is controversial and is based upon the injury pattern and the surgeon's experience and preference. This article reviews the pertinent anatomy, mechanism of injury, evaluation, and treatment of patients with carpometacarpal joint injuries. PMID- 8196964 TI - Train-versus-pedestrian injuries. Orthopaedic management. AB - Between February 1989 and February 1993, a retrospective review at our facility identified 30 patients who were victims of train-versus-pedestrian accidents. Although some patients suffered head, chest, and abdominal injuries, the majority of injuries sustained were musculoskeletal. The Injury Severity Score ranged from 5 to 54, with an average of 21. Of the 30 patients, 23 (77%) had significant orthopaedic injuries, with an average of 1.7 extremities involved. The foot was the most commonly injured body segment, sustaining amputation, crush, or degloving injury in 12 patients (12/23 = 52%). The most common operative procedure was debridement, which was performed largely on patients with traumatic amputation in an effort to preserve length. Nineteen lower extremity and 2 upper extremity amputations were necessary in 14 patients (an amputation rate of 14/23 = 61%). With the exception of toe and heel avulsion, nearly all crush and avulsion injuries required amputation at a segment higher than the level of injury. Although image of an unstable patient with mangled extremities, many patients survive low-velocity collisions and subsequently require vigorous orthopaedic intervention. PMID- 8196965 TI - Intramedullary nail and lag-screw fixation of proximal femur fractures. Operative technique and preliminary results. AB - Fifty patients with intertrochanteric and subtrochanteric fractures of the femur were treated with closed reduction and internal fixation with Vector intramedullary nail (Biomet Inc, Warsaw, Indiana) and lag-screw fixation. Sixty five percent of intertrochanteric fractures were unstable, with subtrochanteric extension in 12 cases. Lag-screw fixation preceded closed, unreamed nailing. Weight bearing, as tolerated, was initiated on the first post-operative day in all patients. Overall mortality and complications were lower than those reported in comparable series of intertrochanteric fractures treated with internal fixation. One nail breakage occurred. No cases of lag-screw cutout, nonunion, or femoral shaft fracture were documented. The Vector nail has recently been introduced as an alternative form of fixation for complex proximal femur fractures. In the present study, consistently good results were obtained, despite the stability or location of the fracture. We especially recommend using the Vector nail for managing complex, unstable intertrochanteric and subtrochanteric fractures. PMID- 8196966 TI - The treatment of open and/or unstable tibial fractures with an unreamed double locked tibial nail. AB - A multicenter, prospective study was conducted to assess the efficacy of an unreamed, double-locked tibial nail for the acute management of open and/or unstable tibial fractures. Seventy-seven acute unstable and/or open tibial fractures in 74 patients were treated from December 1986 to February 1989. Forty fractures were closed and 37 were open; 25% occurred in polytraumatized patients and 39% of the patients had additional fractures. All closed tibial fractures healed at an average of 14.2 weeks; 94.6% of the open tibial fractures healed at an average of 20.1 weeks. There were no infections in the closed tibial fracture group. There were 4 infections among the 37 patients (11%) in the open tibial fracture group, 2 superficial and 2 deep. There were 7 problems intraoperatively (8.4%) with fin deployment: 2 fins bent during nail insertion, 4 fins penetrated the cortex, while 1 set of fins only partially deployed. Difficulty was encountered with proximal screw insertion in one third of the cases. Considering the high energy of these injuries, the treatment of open and/or unstable tibial fractures with an unreamed, double-locked tibial nail can offer the surgeon a high rate of union (97%) with minimal complications. The low infection rate found in this series indicates that this nail may be of particular benefit in the treatment of closed and select open tibial fractures. PMID- 8196967 TI - Into the knee with needle and steroids. PMID- 8196968 TI - An effective technique for corticosteroid injection into the knee joint. PMID- 8196969 TI - An effective technique for corticosteroid injection into the knee joint. PMID- 8196970 TI - The incidence, pathogenesis, diagnosis, and treatment of fat embolism. AB - Fat embolism syndrome is a potentially serious and life threatening complication of long bone trauma, blunt trauma, and intramedullary manipulation. In long bone fractures, fat embolism is encountered in 0.9% to 2.2% of cases. During intramedullary manipulations, such as prosthetic stem insertion or reaming, the incidence is typically lower (range, 0.5% to 0.8%). Diagnosis is dependent upon the clinical recognition of dyspnea, petechiae, and cognitive dysfunction in the first several days following fracture, trauma, or intramedullary surgery. Treatment consists of pulmonary support and aggressive resuscitation. Studies support early fracture fixation, but the role of systemic steroids, heparin, and other modalities remains speculative. PMID- 8196971 TI - Injuries to the acromioclavicular joint. Diagnosis and management. AB - Injuries to the acromioclavicular (AC) joint are common in athletes. Diagnosis can often be made clinically, but radiographs are needed to classify the severity of injury. Treatment is often conservative, consisting of immobilization or symptomatic modalities. Surgery is generally performed on patients with the more severe injuries. Controversy surrounds the treatment of type III injuries. The current trend is toward nonsurgical options, consisting of either symptomatic treatment or immobilization. If surgery is necessary, coracoclavicular (CC) fixation is currently the treatment of choice. PMID- 8196972 TI - Cubital tunnel syndrome. Part I: Presentation and diagnosis. AB - Cubital tunnel syndrome is the second most common entrapment neuropathy after carpal tunnel syndrome. This condition may arise without an obvious compression injury or may be secondary to nerve enlargement or narrowing of the cubital tunnel. Clinical symptoms, radiographic and electrophysiologic findings, and the differential diagnosis of cubital tunnel syndrome are reviewed. PMID- 8196973 TI - Complications of internal fixation of tibial plateau fractures. AB - All cases of displaced tibial plateau fractures treated by open reduction and internal fixation at two university hospitals over a 3-year period were retrospectively reviewed. There were 47 fractures in 45 patients. Rigid fixation to allow early motion was the goal in all cases. There were 3 AO type I (wedge) fractures, 20 AO type III (wedge/depression) fractures, and 24 AO type IV (comminuted/bicondylar) fractures. Cases were classified into three groups depending on the amount of hardware used to obtain fixation (a single buttress plate, group 1; a buttress plate and interfragmentary lag screws, group 2; or medial and lateral buttress plates with or without lag screws, group 3). In group 1, there were 20 fractures and no instances of deep-wound infection or postoperative ankylosis. In group 2, infection occurred in 6 of 19 fractures (32%), all of which also developed significant ankylosis including 1 patient who underwent arthrodesis. In group 3, 7 of 8 (87.5%) knees became infected, and the patients experienced other devastating complications, including ankylosis (n = 3), arthrodesis (n = 2), knee disarticulation (n = 1), and above-knee amputation (n = 1). Patients whose knees became infected underwent an average of five subsequent surgical procedures. These results suggest that patients with comminuted tibial plateau fractures requiring either two buttress plates or a single plate with additional interfragmentary lag screws would probably be better managed by either non-operative treatment or limited internal fixation. PMID- 8196974 TI - Glenohumeral abnormalities associated with full-thickness tears of the rotator cuff. AB - One hundred consecutive patients with full-thickness tears of the rotator cuff were prospectively evaluated by glenohumeral arthroscopy to determine the incidence of associated intra-articular lesions. Seventy-four of the 100 patients had coexisting intra-articular abnormalities. PMID- 8196975 TI - A longitudinal tibial stress fracture. AB - Tibial stress fractures are common in an athletic population. The patient is usually an athlete who is involved in highly repetitive impact activities that have increased in intensity, and who develops pain over the anterior tibia that is felt with exercise and relieved by rest. Physical examination usually reveals focal bony tenderness. Plain roentgenograms initially tend to be normal, and bone scan is the gold standard for diagnosis. Most tibial stress fractures are transverse or oblique. The authors present the first reported case of an activity related longitudinal stress fracture of the distal tibia in a previously healthy, premenopausal woman. A discussion of this unusual presentation, its radiographic appearance, and its response to treatment is presented. PMID- 8196976 TI - Grade III avulsion fracture repair on the UCL of the proximal joint of the thumb. AB - A technique is presented for repair of grade III avulsion fractures of the ulnar collateral ligament when the bony avulsion fragment in the thumb is too small or too comminuted to allow simple repair. The case presented demonstrates that a single suture-to-bone anchor can provide secure ligament fixation without the need for external pull-out wires or buttons and can make possible an early return to activity. PMID- 8196977 TI - A 73-year-old woman with stiffness in both hands. AB - The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopaedic surgeon. Initial history, physical findings, and roentgenographic examinations are found on the first page. The final clinical and roentgenographic differential diagnoses are presented on the following pages. PMID- 8196979 TI - The ritual at the scrub sink. PMID- 8196978 TI - Appropriate techniques for musculoskeletal tumor biopsy. AB - Despite the crucial nature of a biopsy for the diagnosis and treatment of a musculoskeletal tumor, the basic tenets of biopsy technique are frequently not respected. Unfortunately, catastrophic errors in biopsy technique occur frequently. Examples of the more common errors and the correct surgical techniques are discussed. PMID- 8196980 TI - Neurological sequelae of acute bacterial meningitis. PMID- 8196981 TI - Should general pediatricians treat their patients who have bacterial meningitis? PMID- 8196982 TI - Epidemiology of bacterial meningitis. PMID- 8196983 TI - Meningitis: clinical presentation and workup. PMID- 8196984 TI - Antimicrobial treatment and prevention of meningitis. AB - The efficacy of the conjugate polysaccharide H influenzae type b vaccine has resulted in a reduction in the number of cases of meningitis. Physicians will manage fewer cases of meningitis but they must maintain skills in diagnosis and treatment of the cases that do occur. In addition, to a continuing experience with meningitis due to S pneumoniae and N meningitidis, physicians must be aggressive in obtaining materials for specific diagnosis of aseptic meningitis since many of the infections are treatable with antimicrobial agents. Appropriate treatment of meningitis in children requires knowledge of agents for initial therapy, dosage schedules, changes in the regimen that may be required once the organism is isolated and results of susceptibility tests are available, knowledge of the drugs that require monitoring of serum concentrations to determine safety and efficacy, and antimicrobial prophylaxis for contacts. PMID- 8196985 TI - Dexamethasone therapy in bacterial meningitis. AB - With improved understanding of the pathophysiology of bacterial meningitis, a number of points in the deleterious inflammatory cascade have been identified as possible sites for modulation. Dexamethasone attenuates tissue injury by inhibiting host mediators at several steps in the inflammatory process. Dexamethasone therapy initiated just before or simultaneously with the first parenteral antibiotic dose is recommended for infants older than 6 weeks of age and children with bacterial meningitis. A beneficial effect of steroid therapy administered 12 to 24 hours or more after the first dose of parenteral antibiotics is unlikely. The consistent finding of improved overall neurologic outcome in infants and children with bacterial meningitis caused by the usual meningeal pathogens treated with dexamethasone is the basis for this recommendation, provided that the caveats discussed above are observed. PMID- 8196986 TI - Bacterial meningitis: fluid balance and therapy. AB - Fluid administration in children with meningitis should be conservative in an attempt to minimize cerebral edema and electrolyte disturbances that frequently complicate the course of meningitis. Since these complications have been shown to correlate with poor neurologic outcome, it is believed that appropriate fluid management will minimize the morbidity and mortality associated with bacterial meningitis in children. PMID- 8196987 TI - Recent advances in the treatment of cystic fibrosis. AB - Cystic fibrosis is a serious, common genetic condition that causes recurrent pulmonary infections, malabsorption, and increased sweat electrolytes. Despite significant improvements in clinical treatment, individuals continue to die from progressive, obstructive pulmonary disease as children and young adults. This article reviews the current status of our understanding of cystic fibrosis: the basic defect, animal models, current therapy, and new approaches to the pulmonary disease. PMID- 8196988 TI - Congenital malformations of the lung. AB - Congenital malformations of the lung are a frequent cause of abnormal chest radiographs in neonates and young children as well as a common cause for recurrent pneumonia in older patients. Based on the mode of presentation and clinical findings along with an understanding of lung embryology, one can develop a thorough differential diagnosis that allows for the evaluation of the lesion in question. Appropriate management of the patient can then be undertaken with a minimum of diagnostic studies and without any delay in treatment. PMID- 8196989 TI - Nursing management of the child with a tracheotomy. AB - The management of medically fragile children with tracheotomies can be challenging to the pediatrician. This management includes the well child care for these children as well as coordination of the often complex care associated with the underlying condition. Various diseases exist that cause airway obstruction, respiratory failure, or chronic aspiration, necessitating tracheotomies. Tracheotomies require astute observation and skilled care to minimize complications. PMID- 8196990 TI - Respiratory failure in congenital heart disease. AB - Infants and children with congenital heart disease (CHD) present unique difficulties when they develop respiratory failure, either as a consequence of their heart disease, in relation to cardiac surgery, or from infectious causes. Extensive cardiac surgical repairs are now being performed on younger infants with complex anatomy and physiology. The evolution of cardiac surgical technique and perioperative management has revealed the importance of subtle interactions between respiratory physiology and hemodynamic performance. PMID- 8196991 TI - Interstitial lung disease in children. AB - Interstitial lung disease in children is a heterogeneous group of disorders of both known and unknown causes that share a common histologic characteristic (i.e., inflammation of the pulmonary interstitium that may resolve completely, partially, or progress to derangement of alveolar structures with varying degrees of fibrosis). The inflammatory process, evoked as a result of injury to alveolar epithelium and/or the endothelium, is responsible for alveolar wall thickening that is the histologic marker of ILD. This article extrapolates some of the known pathogenic mechanisms of ILD from adult and animal models and applies this information for a better understanding of the pathogenesis of ILD in children. The clinical manifestations vary and are often subtle and nonspecific. There is no consensus on specific criteria for the clinical diagnosis of ILD in children. There are no pathognomonic laboratory criteria for the diagnosis of ILD in children other than the characteristic findings on histologic examination of the lung. It is important to make the diagnosis early to minimize lung damage. Therapy is directed toward the reduction of the inflammatory response to minimize or prevent the progression to fibrosis. ILD suffers from lack of uniform guidelines for diagnostic evaluation, therapy, and prognostic indicators essential for critical monitoring of disease activity. No one medical center has enough cases of ILD in children to allow objective evaluation of a significant number of cases with adequate longitudinal follow-up to determine guidelines for optimal management and to identify accurate prognostic indicators. The organization of a multicenter approach will guide us towards a better understanding of ILD in children. PMID- 8196992 TI - Pulmonary embolism in children. AB - Pulmonary embolism is an uncommon diagnosis in the pediatric patient, often discovered on autopsy. The mortality rate of untreated pulmonary embolism approaches 30%, and the best way to prevent death is by swift diagnosis and initiation of therapy. This article reviews the risk factors, clinical presentation, pathophysiology, diagnostic modalities, and treatment of pulmonary embolism in children. PMID- 8196993 TI - Continued pulmonary recovery observed after discontinuing extracorporeal membrane oxygenation. AB - Extracorporeal membrane oxygenation (ECMO) is a valuable therapy for the treatment of reversible lung disease in neonates. Associated with this treatment, however, are risks for complications that increase with the duration of therapy. We evaluated alveolar-arterial oxygen tension difference P(A-a)O2 pulmonary compliance (CL), and functional residual capacity (FRC) in 20 infants immediately after ECMO was discontinued, and again 24 hours thereafter. We measured CL by pneumotachography and esophageal manometry and FRC by helium dilution. Mean (+/- SEM) values for CL and FRC increased (CL from 0.28 +/- 0.02 to 0.35 +/- 0.03 mL/cmH2O)/kg and FRC from 18.6 +/- 1.4 to 22.2 +/- 1.1 mL/kg; P < 0.05), and P(A a)O2 and the oxygenation index (OI) decreased (200 +/- 19 to 169 +/- 14 mm Hg and 6.9 +/- 0.44 to 5.4 +/- 0.5, respectively; P < 0.02), over the 24 hour period following ECMO. Nineteen of 20 infants experienced improvement in at least two of these parameters. Improvements were found to be greatest in the infant with the worst lung function immediately after discontinuing ECMO, and in the ten infants who had not received pancuronium bromide for inducing skeletal muscle paralysis, following decannulation from ECMO. These data indicate that improvement in lung function following ECMO will generally continue over the 24 hour period following the termination of cardiopulmonary bypass, and that borderline pulmonary status may not preclude discontinuation of bypass therapy. PMID- 8196994 TI - Influence of head-neck posture on airflow and pulmonary mechanics in preterm neonates. AB - The influence of head-neck posture (neutral, 15 degrees, 30 degrees, and 45 degrees extension and flexion) on airflow and pulmonary mechanics was evaluated in 10 spontaneously breathing healthy preterm neonates (mean +/- SD; birth weight, 1.32 +/- 0.23 kg; gestational age, 29.4 +/- 2.4 weeks; study age, 36.6 +/ 1.6 weeks) who had had respiratory distress syndrome. Head-neck postures were quantified using specially constructed wooden wedges. Airflow was measured by a pneumotachometer via face mask. Lung compliance (CL) and resistance (RL) were measured using an esophageal balloon. Airflow interruption was designated as mild (10-40%), moderate (40-80%), and severe (> 80-100%) decrease of airflow. At neutral head-neck posture, 42.8 +/- 7.5% SEM of breaths had airflow interruption (71.4% mild, 19.9% moderate, 8.7% severe). There was no significant change with 15 degrees and 30 degrees head-neck flexion and extension. However, at 45 degrees flexion the overall incidence of airflow interruption (77.3 +/- 4.8%, P < 0.05) and RL (86.6 +/- 6.7 vs. 64.2 +/- 3.9 cmH2O/L/s, mean +/- SEM; P < 0.05) significantly increased. Extension to 45 degrees caused severe airflow interruption and increased RL in some infants, but no statistically significant change for the whole group. The incidence of severe airflow interruption significantly increased (P < 0.05) from 8.7% at neutral head-neck posture to 26.3% at hyperflexion (45 degrees). No changes in CL were observed. We conclude that minor (15-30 degrees) deviations from neutral neck posture are insignificant, whereas hyperflexion, and in some infants, hyperextension, can significantly affect airflow and pulmonary mechanics. PMID- 8196995 TI - High frequency jet ventilation: intraoperative application in infants. AB - The potential advantages of the intraoperative use of high frequency jet ventilation (HFJV) when compared with conventional ventilation (CV) include the maintenance of adequate gas exchange and lung function with a relatively motionless surgical field. To determine the pulmonary response to HFJV ventilation in infants during cardiac surgery, we evaluated lung function in nine infants supported with CV and HFJV during a Blalock-Taussig shunt procedure. Infants were randomized to each mode of ventilation with inspiratory and expiratory pressures and FiO2 held constant. Heart rate, blood pressure, arterial blood gases, pulmonary mechanics (lung compliance and resistance), and functional residual capacity (FRC) were compared after 10 minutes of stabilization of each ventilation mode, with the infants in the thoracotomy position and the surgical field adequately exposed. Pulmonary mechanics were measured using esophageal manometry and pneumotachography, and FRC by helium dilution. There was no difference in vital signs, pulmonary mechanics, FRC, or PaO2 on HFJV ventilation when compared with CV. Arterial PaCO2 was lower with a lower mean airway pressure on HFJV when compared with CV. The surgical team subjectively observed a diminished need for lung manipulation and improved ease of access to the surgical field with HFJV. These results indicate that the use of HFJV during closed-heart cardiac surgical procedures in infants provides similar cardiopulmonary stability and some potentially important clinical benefits when compared with CV. PMID- 8196996 TI - Continuous negative extrathoracic pressure versus positive end-expiratory pressure in piglets after saline lung lavage. AB - Recent reports have suggested that substituting continuous negative extrathoracic pressure (CNEP) for positive end-expiratory pressure (PEEP) may result in clinical benefits to infants with pulmonary disease. Other studies have suggested potential hemodynamic advantages. We compared the effects of CNEP and PEEP in 13 mechanically ventilated newborn piglets after acute lung injury induced by saline lavage. The piglets were instrumented, saline-lavaged, and exposed to 15 minute periods of incremental CNEP (-3, -6, -9, -12 cmH2O) (n = 7) or PEEP (3, 6, 9, 12 cmH2O) (n = 6). We measured and/or calculated dynamic lung compliance (CLdyn), lung resistance (RL), end-expiratory lung volume (EELV), blood gases, cardiac output (CO), heart rate (HR), transmural vascular pressures, and pulmonary and systemic vascular resistance. Pulmonary function abnormalities after saline lavage included decreased PaO2, CLdyn, EELV, and increased PaCO2 and RL (P < 0.05). Except for decreased CO, lung inflation with both CNEP and PEEP resulted in large increases in PaO2 without major pulmonary or hemodynamic effects. Other than differences in EELV at 3, 6, and 9 cmH2O distending pressure, there were no differences in pulmonary function or hemodynamics between sequences of incremental CNEP and PEEP. We conclude that CNEP and PEEP are physiologically equivalent in this model of acute lung injury. PMID- 8196997 TI - Acute effects of ambient ozone on respiratory function of Swiss schoolchildren after a 10-minute heavy exercise. AB - This study was conducted in Switzerland between May and October 1989 to assess possible decrements in lung function occurring as a result of 10 minute exposure to ambient air containing different ozone concentrations. Once a month, 128 children in two different areas of Southern Switzerland (Chiasso and Aurigeno) had a pulmonary function test before and after a standardized 10 minute exercise (pulse rate, 170/min) on a cycle ergometer, outdoors. Ozone concentrations were similar in both areas, ranging from 40 to 157 micrograms/m3 (1/2h means) during the exercise tests. The two communities differed with respect to long-term average pollution levels. The mean NO2 concentration over the six months study period was 70 micrograms/m3 in Chiasso and 18 micrograms/m3 in rural Aurigeno. Of the eligible children 85% participated and attended 4-6 tests. Parents completed a standardized questionnaire on family background, home characteristics and the child's early and present illness history. A total of 500 acceptable pairs of spirograms and corresponding ozone concentrations (average 3.8 per child) were available for analysis. Regressions of each individual's pre-post differences of FVC, FEV1 and peak flow on ozone concentrations measured during the outdoor exercise indicated that elevated ozone levels significantly reduced peak flow values. Adjustments for temperature and relative humidity increased the magnitude of the peak flow slopes. The average adjusted regression coefficient for delta peak flow on ozone was -2.28 mL/s/micrograms/m3 (95% CI, -0.57 -3.99). It is noteworthy that the observed relationships occurred at ozone concentrations below 160 micrograms/m3 and after an exercise duration of only 10 minutes. PMID- 8196998 TI - Disease severity and optimum mean airway pressure level on transfer to high frequency oscillation. AB - The aim of this study was to assess whether the severity of the infant's lung disease determined the most appropriate change in mean airway pressure (MAP) level to use on transfer from conventional ventilation to high frequency oscillation (HFO). In addition, we wished to assess whether the oscillatory frequency employed affected gas exchange. Ten premature infants with respiratory distress syndrome (RDS) were studied at a mean postnatal age of 1.5 days. During HFO, the infants were studied at a MAP equivalent of that used during conventional ventilation (baseline MAP), then at 2 and 5 cmH2O above baseline at 10 Hz. At the MAP identified as optimum, that is, the one associated with the best oxygenation, the infants were then studied at 10, 15 and 20 Hz. Each oscillatory setting was maintained for 20 minutes after which time arterial blood gases were measured. Prior to transfer to the oscillator, the peak inspiratory pressure was recorded, the P(A-a)O2 calculated and compliance of the respiratory system (Crs) measured. In nine infants, the optimum baseline MAP was +5 cmH2O. Oxygenation at that level was better than on conventional ventilation (P < 0.05), but there was no significant change in CO2 elimination. The optimum MAP was related to the peak pressure during conventional ventilation (P < 0.01) and inversely related to Crs (P < 0.01). There was no significant relationship with the P(A-a)O2. At the optimum MAP, the only significant effect of frequency was an impairment of oxygenation at 20 Hz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8196999 TI - Variations in flows and pressures during jet ventilation in the infant: a model study. AB - Ventilatory flow rates with either He-O2 (heliox) or N2-O2 (nitrox) mixtures during high frequency jet ventilation (HFJV) were calculated using a mathematical model, and were measured in a physical monoalveolar model of the infant lung. A constant flow was delivered to the model (Vd) drawing with it an entrained flow (Ve). When the inspiratory time (Tl) was long, a back flow (Vr) was generated that increased progressively as the alveolar pressure increased. In order to reduce Vr, the reflux time (Tr), i.e., the time needed for the injected gas to reflux, was measured (Trm) and calculated (Trc) with the model. The Tr depends on both chest-lung compliance and resistance to reflux as well as on the Ve/Vd ratio. For a given setting of the ventilator, values of Trm and Trc were significantly lower with heliox than nitrox (P < 0.01), and the correlation between Trm and Trc were fair with both gases. Tidal volume (VT) was calculated when the Tl was interrupted at Tr. The values of VT were significantly higher with helix than nitrox (P < 0.05). It is concluded that the evaluation of Tr during HFJV may provide useful information for setting the ventilator. PMID- 8197000 TI - Infrared end-tidal CO2 measurement does not accurately predict arterial CO2 values or end-tidal to arterial PCO2 gradients in rabbits with lung injury. AB - End-tidal PCO2 (PETCO2) measurements from two commercially available neonatal infrared capnometers with different sampling systems and a mass spectrometer were compared with arterial PCO2 (PaCO2) to determine whether the former could predict the latter in mechanically ventilated rabbits with and without lung injury. The effects of tidal volume, ventilator frequency and type of lung injury on the gradient between PETCO2 and PaCO2 (delta P(a-ET)CO2) were evaluated. Twenty rabbits were studied: 10 without lung injury, 5 with saline lavage and 5 with lung injury by meconium instillation. Paired measurements of PETCO2 by two infrared capnometers and a mass spectrometer were compared to PaCO2. In the rabbits without lung injury, the values from the infrared capnometers and mass spectrometer correlated strongly with PaCO2 (r > or = 0.91) despite differences in the slopes of the linear regression between PETCO2 and PaCO2 and in delta P(a ET)CO2 (P < 0.05). Values from the mainstream IR-capnometer more closely approximated the line of identity than the regression between the sidestream IR capnometer values or the mass spectrometer and PaCO2, but tended to overestimate PaCO2. The delta P(a-ET)CO2 was similar at all tidal volumes and ventilator frequencies, regardless of capnometer type. In the rabbits with induced lung injury, while there was a positive correlation between the slopes of the regression between PETCO2 and PaCO2 for both capnometers (r > or = 0.70), none of the regression slopes approximated the line of identity. The delta P(a-ET)CO2 was greater in rabbits with injured than noninjured lungs (P < 0.05). The delta P(a ET)CO2 was similar among capnometers regardless of tidal volume, ventilator frequency, or type of lung injury. The 95% confidence interval of plots PaCO2 against PETCO2 was large for rabbits with injured and noninjured lungs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8197001 TI - Fatal pulmonary involvement in a patient with familial hemophagocytic lymphohistiocytosis. PMID- 8197002 TI - Tracheoesophageal fistula induced by aspergillus infection following bone marrow transplantation. PMID- 8197003 TI - On dexamethasone in bronchopulmonary dysplasia. PMID- 8197004 TI - Drug trafficking among African-American early adolescents: prevalence, consequences, and associated behaviors and beliefs. AB - OBJECTIVE/METHODOLOGY: Drug trafficking by minority youths in low-income, urban areas has received considerable publicity from the mass media in the past half decade. However, there has been corresponding little exposition of this problem in the medical literature. This review was undertaken to provide an overview of the epidemiology and consequences of drug trafficking among urban youths and to describe factors associated with drug trafficking. RESULTS: Existing data indicate that approximately 10% of male, urban, African-American early adolescents report having engaged in drug trafficking, with a higher percent of youths reporting having been asked to sell drugs and/or indicating that they expect to become involved in drug trafficking. Rates increase with advancing age. Reported rates of drug trafficking are comparable with rates of tobacco and alcohol use among early adolescents and are substantially higher than use rates of illegal drugs. Drug trafficking is associated with increased mortality, accounting for one third to one half of homicide-related deaths in some studies. The practice is also associated with other health-risk behaviors, including nonfatal violence, substance use, and incarceration. Perceived social pressures by family members and/or peers to engage in drug trafficking and the belief that a youth's wage-earning potential is limited to drug trafficking are highly correlated with involvement in this activity. CONCLUSIONS: Drug trafficking is a prevalent risk behavior among adolescents that has several negative health consequences. PMID- 8197005 TI - Recent and intended drug trafficking among male and female urban African-American early adolescents. AB - OBJECTIVE: To investigate associations between recent and intended involvement in drug trafficking and perceptions of the social environment among high-risk urban African-American youths. METHODS: A multicomponent risk assessment survey was conducted among a convenience sample of 351 African-American youths 9 through 15 years of age residing in low-income communities. Both univariate analysis and logistic regression were performed to examine the association of youths' perceived social environment with recent and intended involvement in drug trafficking. RESULTS: Drug selling or delivering in the previous 6 months was reported by 6% of the youths; 12% expected to engage in these activities in the next 6 months. There was a strong association between drug trafficking and other high-risk behaviors, including drug use. Among both genders, perceptions that neighbors, friends, or family members were involved in drug trafficking were correlated with recent or intended drug trafficking. For boys, personal economic needs had a strong association with drug trafficking. For girls, personal feelings were more important correlates of intended involvement. CONCLUSIONS: Efforts aimed at both drug-trafficking prevention and intervention need to be community-based and multifaceted. Programs should address the youths' perceived social environments and consider gender differences regarding correlates of drug trafficking involvement. PMID- 8197006 TI - The "hustle": socioeconomic deprivation, urban drug trafficking, and low-income, African-American male gender identity. AB - OBJECTIVE: Drug trafficking seems to be both prevalent and associated with considerable morbidity and mortality among inner-city African-American males. Survey data has indicated the possible importance of economic need in the rapid emergence of drug trafficking in this population. In the present study, an historical-cultural approach is used to examine this economic relationship further and to explore the role that drug trafficking plays in a society that has permitted its successful and rapid growth. METHODOLOGY: Data were obtained from interviews of approximately 600 African-Americans residing in inner-city neighborhoods in Washington, DC and Baltimore during nine drug- and acquired immunodeficiency syndrome-related studies conducted over 4 years. RESULTS AND CONCLUSIONS: From the perspective of the study participants, the need to provide economic support for one's family as well as to achieve some sense of status, respect, and reputation among one's peers are two core constructs of masculine identity in the United States. The historical and worsening inequities in access to economic resources and power by African-American males are viewed as significantly reducing the opportunity for economic success through more social or legal enterprises. Pursuit of nonmainstream activities (such as drug trafficking) is perceived as offering an opportunity for economic advancement and for establishing a power base for individuals who have been denied access to mainstream opportunities. PMID- 8197007 TI - Life choices of African-American youth living in public housing: perspectives on drug trafficking. AB - OBJECTIVE: Our understanding of youth involvement with drug trafficking is derived mainly from survey data. Personal narratives present the life choices that low-income, urban African-American youth perceive and the decisions that they make. Narratives provide insight into the complexities inherent in those choices. METHOD: Twenty youth were interviewed through semiclinical, open-ended interviews. Youths were asked to describe their perceptions of how people their age make choices about becoming involved or refraining from involvement in drug trafficking. Data were analyzed within the context of psychological factors which influence child development, including attributions of personal meaning and identity formation. RESULTS AND CONCLUSION: Youth narratives reflect an awareness of the contradictory messages present within their environments. Youth articulate the importance of family and peer influences on their decisions to engage in or refrain from drug trafficking. Their perceptions of themselves as belonging to a racial minority group also influence their views regarding the viable alternatives available to them for achieving success. Youth who are able to identify alternative activities from which they can derive positive experiences are less likely to become involved in drug trafficking. Recommendations for intervention at the familial, community, and institutional levels are discussed. PMID- 8197008 TI - Parental monitoring and peer influences on adolescent substance use. AB - OBJECTIVE: To examine the joint influences of parental monitoring and peer influence on adolescent substance use over time. SUBJECTS: 6500 adolescents attending six high schools in Wisconsin and northern California. DESIGN: Longitudinal study. RESULTS: Parental monitoring was negatively associated with substance use, whereas the more involved an adolescent's peers were in substance use, the more likely he or she also was to use drugs and alcohol. Effects of monitoring and peer coercion were strongest for boys and girls at the transition into substance use, rather than at the transition from experimentation to regular use. The effect of parental monitoring on changes in adolescent substance use is mediated not so much by the nature of the adolescent's peer associates, but by its direct effect on the adolescent. Specifically, poorly monitored adolescents are more likely to use drugs, and drug-using adolescents seek out like-minded friends. Once an adolescent associates with drug-using peers, his or her own substance use approaches their level. CONCLUSIONS: Intervention effects should include both parents and community-level efforts. Parental monitoring is an effective tool both in the prevention of drug use and in the amelioration of drug use. PMID- 8197009 TI - Drug use, drug trafficking, and weapon carrying among low-income, African American, early adolescent boys. AB - OBJECTIVE: To examine relationships involving three extremely high-risk behaviors (drug use, drug trafficking, and weapon carrying) among low-income, urban, African-American early adolescent boys using both quantitative and qualitative methods. METHOD: The quantitative phase included 192 African-American boys from 9 through 15 years of age recruited from recreation centers located in low-income communities. Youth completed a survey addressing personal risk practices; intentions to engage in risk practices; risk taking among family, friends and community; and values toward risk practices. They also completed standardized assessments of sensation seeking, perceived peer pressure, and parent-child communication. All questionnaires were self-administered through MacIntosh computers programmed to present questions aurally and visually. The qualitative phase included 12 African-American youth from low-income, urban families. The youth participated in 60- to 90-minute interviews regarding drug activities and violence. RESULTS: Most boys (73%) were not involved in either drug activities or weapon carrying. Boys who were involved in drug activities or weapon carrying were often involved in other high-risk activities (cigarette and alcohol use, school failure and expulsion) and had low rates of adaptive communication with their parents. The boys reported high rates of drug involvement by their family, friends, and community. However, psychological and interpersonal factors were better predictors of individual risk activities than community or family variables. Personal values regarding economics predicted drug trafficking. More than 56% of the boys who reported past involvement in drug activities did not anticipate future involvement. CONCLUSIONS: Multilevel strategies are necessary to prevent involvement in drug activities and weapon carrying. Intervention programs should begin early and should promote communication between parents and children, adaptive behavior in school, and avoidance of cigarette and alcohol use. Community-level interventions are needed to alter the myth that drug involvement and weapon carrying are normative and to promote images that are less materialistic and more supportive of education and future-oriented activities. PMID- 8197010 TI - Using mass media to reduce adolescent involvement in drug trafficking. AB - OBJECTIVE: Drug trafficking among adolescents is a newly recognized high-risk behavior that seems to be involving large numbers of youths. Strategies to prevent and/or alter this behavior must be developed and evaluated. In view of the high exposure of adolescents to the mass media, interventionists seeking to reduce adolescent risk behavior have increasingly employed the media in their efforts to reduce adolescent risk behaviors in general. However, not all risk behaviors may be amendable to change as a result of this approach. Therefore, before utilizing this approach to address adolescent drug trafficking, it is important to investigate previous efforts targeting related risk behaviors. RESULTS: Mass media campaigns against the use of drugs have been common in the US and seem to have played a role in reducing consumption of both legal and illegal drugs. The most effective messages seem to focus on the risks of drug use and the social disapproval that attends use. The mass media may increase the influence of these antidrug messages by changing the social climate surrounding drug use. CONCLUSIONS: The mass media may be a particularly effective way to reach adolescents and their parents in communities in which adolescent drug trafficking is prevalent and to unite the institutions that could influence adolescents against involvement in the drug trade. However, intervention efforts must also contend with the economic incentives of the drug trade in poor, central-city communities. PMID- 8197011 TI - African-American youth: drug trafficking and the justice system. AB - OBJECTIVE: To examine the role of the legal system in adolescent drug trafficking. METHODS: Descriptive and analytic review of the literature and relevant legislation. FINDINGS: Utilization of young adolescents by drug "kingpins" in drug trafficking is a new practice that is highly advantageous to the employer for several legal and economic reasons. From the perspective of the drug kingpins, juveniles are particularly useful in drug trafficking because they work for lower wages. Further, even if the youth are arrested, the juvenile justice system enables their rapid return for continued service in the drug trade. From the perspective of the youth, drug trafficking offers one of the few economic opportunities available to them. Further, the numbers suggest a tremendous racial disparity in the juvenile justice system. CONCLUSIONS: The mutual advantages to both employer and employee of using youths in drug trafficking increases the likelihood that this new practice will continue to flourish and with increasingly young children. Effective prevention and treatment interventions will need to be multifaceted, addressing the economic, educational, and social issues that have permitted the rapid emergence of adolescent drug trafficking. Finally, further investigation of the apparent racial disparities is necessary. PMID- 8197012 TI - [Current trends in the treatment of malformative uropathies]. AB - Urinary tract malformations are common malformations. Surgical correction is very often required to normalize the urinary tract and to prevent renal function deterioration or to ameliorate a compromised renal function. The results of the surgical management have had a considerable improvement in the last decades. Three mechanisms worked at this regard: 1) the possibility of antenatal ultrasound diagnosis; 2) a better knowledge of the natural postnatal evolution; 3) the long-term results of the surgical treatment. Referring to literature's data and especially to a wide personal experience, the Author outlines the correct indications for surgery and the most effective surgical procedures in the management of the most important urinary tract malformations. PMID- 8197013 TI - [Eosinophils: current knowledge and clinical usefulness in childhood]. AB - We describe the eosinophil granulocyte's immunobiology and pediatric management implications. Moreover, we review our results about eosinophil count in newborn as a predictive marker of atopy. PMID- 8197014 TI - [Gastroesophageal reflux and bronchial asthma: pH-metric patterns in non allergic children]. AB - The presence of gastroesophageal reflux (GER) was studied, by computerized 24 hours intraesophageal pH monitoring, in 27 asthmatic children (16 M - 11 F; mean age 75.04 months) without allergy and in absence of medical treatment for at least ten days. Patient were divided in 3 groups: Group A (11 cases): subjects with Reflux Index (R.I. = percentage of time pH < 4) more than 4.2% and with GER percentage of time in standing position > supine position (p < 0.001). Group B (6 cases): subjects with R.I. more than 4.2% and with GER percentage of time in standing position < supine position (p = 0.05). Group C (10 cases): subjects with R.I. less than 4.2%. A group D (10 cases): normal children considered as control. The group A ("daily refluxes") resulted as the most numerous, in contrast to the studies up to now followed. The total number of refluxes resulted with no significant difference in groups A, B and C, but a significant prevalence of this number was noted in the group C against group D. Therefore, the parameter "Total number of refluxes in 24 hours" characterizes in our opinion, on the pH monitoring, children with bronchial asthma and without allergy. PMID- 8197015 TI - [ECG monitoring in full-term infants. Analysis of the rhythm and variability of heart rate]. AB - BACKGROUND: Heart Rate (HR) and Heart Rate Variability (HRV) depend on the neural control to the heart. HRV can be measured from 24-hours function. Little information is available on cardiac rhythm and on autonomic nervous control to the heart at birth. The aims of the study weew: 1) to study the cardiac rhythm in healthy newborn babies; 2) to asses the normal values for HRV at birth. METHODS: We studied 20 full term healthy newborn babies. Newborns underwent 24-hours ECG Holter monitoring. Analysis was performed by a 750 A Del Mar Avionics Analyzer. We determined: Heart Rate (HR), number of extrasystoles, Standard Deviation of all R-R intervals over 24 hours (SDNN) and mean hourly HRV (HRVM). Results about HRV were matched with those of 50 healthy adults. RESULTS: 1) Average HR in the newborn babies was 108 (range: 55-198); we found high prevalence of supraventricular extrasystoles. 2) We determined reference value for HRV. SDNN was 55 +/- 17 ms in newborns. SDNN of adults was 132 +/- 25 ms (44% higher than in newborns; p < 0.001). HRVM was 46 +/- 14 ms in newborns and 76 +/- 14 ms (p < 0.001). CONCLUSION: 1) Larger intervals of HR in newborn babies compared to literature data and an high prevalence of supraventricular arrhythmias in full term healthy newborn babies. 2) Reference values for HRV in newborn babies. The low values of HRV confirm the immaturity of autonomic cardiac control. PMID- 8197016 TI - [Acute osteoarthritis in the newborn and infants]. AB - The Authors report two cases of acute osteomyelitis, in a newborn and in an infant. Bone and joint sepsis in the first years of life is rare. The metaphases of long bones are the most common sites of hematogenous osteomyelitis. The hip and the knee are especially at risk. The patients were treated with pharmacologic and orthopedic therapy. The Authors describe the clinical features, radiographic changes, the diagnosis and management of this disease. PMID- 8197017 TI - [Staphylococcal infection in the newborn: teicoplanin therapy]. AB - Infections caused by Gram-positive bacteria, particularly in neonatal patients, have increased dramatically over the past 10 years. In the present study 19 newborns (7 at term, 12 preterm) with proven staphylococcal infection were treated with teicoplanin, after a previous ineffective antibiotic treatment (amikacin+oxacillin or third-generation cephalosporin). Bacterial eradication and clinical cure were achieved in all neonates. No adverse events related to the drug occurred. No significant change was observed in serial biochemical and hematological tests. Our results suggest that teicoplanin is highly effective and safe in neonatal staphylococcal infections. PMID- 8197019 TI - [Corticosteroid treatment regimes and growth hormone secretion in congenital adrenogenital syndrome]. AB - 11 patients with 21-hydroxylase deficiency were treated with three different corticosteroids and two different distributions of therapy during daytime. We found that: 1) a higher dose of steroid in the evening had a markedly inhibitory effect on nocturnal GH secretion; 2) of the steroids we used, dexamethasone caused the greatest reduction in nocturnal GH secretion; 3) in this study adrenal hormones seem less influenced by the different distribution of the corticosteroids during the 24 hours period. PMID- 8197018 TI - [Cough and vomiting association in an infant: where does the vicious circle start?]. AB - The Authors describe the clinical history and diagnostical problems of a premature twin with the three classical symptoms cough-vomiting-growth retardation in the first year of life. Is the diagnostic route required to stabilize whether this condition is primarily gastroenterological or pulmonary? PMID- 8197020 TI - [Incidence of exercise-induced bronchospasm (E.I.B.) and its correlation with clinical history in children with allergic asthma]. AB - In this study, 65 allergic asthmatic children were evaluated for the presence of exercise induced bronchospasm (E.I.B.). Pulmonary function (volume at 1 second of forced expiration--FEV1; maximal mid-expiratory flow--FEF 25-75; peak expiratory flow--PEF) was assessed before and serially for 20' following treadmill exercise. Only 18 children (27.6%) presented a fall in FEV1 > or = 20%. There was a relationship between severity of asthma and incidence of E.I.B., as children with episodic, frequent and chronic asthma presented respectively 13/55 (23.4%), 2/6 (33.3%) and 3/4 (75%) of positive responses. The presence of E.I.B. cannot be predicted by clinical history, as 15/36 (41.7%) of subjects with positive clinical history had E.I.B., against 3/29 (10.3%) of subjects with negative clinical history (p = n.s.). E.I.B. in asthmatic children is less frequent as reported, correlates with severity of asthma and cannot be accurately predicted from the history. PMID- 8197021 TI - [Antiendomysial antibodies: current role in the diagnosis of celiac disease compared to antigliadin antibodies]. AB - We evaluated in parallel the action of antigliadin (AGA-IgA) and anti-endomysium (EmA) antibodies in a group of 144 coeliac patients during the various diagnostic procedures, and in 277 controls (206 affected by other gastroenterological diseases and 71 healthy or affected by non-gastroenterological diseases, not causing any immune changes). Little difference was observed between the two tests both during the initial phase of the disease and during gluten-free diet. No EmA positivity was observed in controls; AGA-IgA resulted positive in 6.3% of gastroenterological controls and in 5.6% of non-gastroenterological controls. Finally, the sensitivity, specificity and predictability of the two tests were evaluated in a sample of 92 subjects undergoing intestinal biopsy. The results show that the tests have the same sensitivity, but only for EmA 100% specificity was found. PMID- 8197022 TI - [Pilomatrixoma of the parotid region]. AB - Pilomatrixoma, or calcifying epithelioma of Malherbe, is an uncommon, benign, epithelial tumor of the skin that often arises in head and neck regions, in the first 2 decades of life. The report of two cases of pilomatrixoma in the parotid area permits to clarify the clinical features and the problems in the differential diagnosis of these tumors. PMID- 8197023 TI - [Hemangioendothelioma of the liver in the newborn: description of 2 cases]. AB - The infantile hemangioendothelioma of the liver is a rare benign vascular tumor that accounts for some 10% of all primary hepatic masses. Two cases were seen at the Department of Pediatric Surgery of Vicenza's Hospital in the last ten years. Both of patients were females and presented in neonatal period asymptomatic. The first patient was found to have hepatomegaly by pediatrician at six weeks of age, the second was an incidental finding following ultrasound neonatal screening. The Authors outline some difficulties met with differential diagnosis between benign versus malignant hepatic tumors. Explorative laparotomy was considered necessary in both the patients. Liver biopsy was the only surgical procedure performed in the nonresectable tumor. Treatment with corticosteroids finally proved to be successful to determine progressive involution of the tumor. In the resectable form, left hepatic lobectomy was successfully performed because of the progressive size increase of the tumor. PMID- 8197024 TI - [Spontaneous pneumomediastinum in an adolescent]. AB - Spontaneous pneumomediastinum is defined as nontraumatic mediastinal air leak in patients without underlying lung disease. In children and adolescents it is rarely described and is likely to be underdiagnosed. We describe a case. The aetiopathogenesis, clinical findings, diagnosis and treatment are discussed. PMID- 8197025 TI - [Hemimegalencephaly: description of a clinical case]. AB - The Authors describe a case of hemimegalencephaly (HME) which appeared with seizures and severe hypotonia in a twelve days old female new born. The eeg alterations aroused of HME suspicion, confirmed from the cerebral TAC. Later on clinical characteristics showed a serious worsening of the illness. THe exitus was caused from the status epilepticus when the child was eight months old before hemispherectomy. Medical and surgical treatments are discussed pointing out the indications and the complications of hemispherectomy. PMID- 8197026 TI - [Infibulation practice: clinical aspects in an adolescent outside the community]. AB - Because of the increase arrival of extra-community people, now it is easy to meet with new pathologies or with old ones that we believed disappeared. We describe a case of infibulation practice observed in a thirteen year old coloured adolescent. She was admitted for an unknown-provenance fever. PMID- 8197027 TI - [Cholesterol cholelithiasis. A clinical case]. AB - The Authors present a case of cholesterinic cholelithiasis, in a patient 13 years of age. The case is interesting because the cholesterol gallstones are uncommon in childhood, with women showing a higher prevalence than men. PMID- 8197028 TI - [Osteoarthritis caused by Brucella melitensis: isolation of the microorganism from the synovial fluid]. AB - Brucellosis is an unusual disease in childhood but the organ manifestations are even more unusual. The Authors describe an osteoarthritis caused by Brucella melitensis, localized at the tarsal scaphoid in a three years old Calabrian child. PMID- 8197029 TI - [Liver abscess: is drug therapy only possible?]. AB - We describe a case of liver abscess, whose favourable evolution, after the initial medical treatment, started when we didn't know the diagnosis, persuaded us to continue the begun treatment, based on localization of disease and on clinical improvement, instead of carrying out on evacuative puncture. At moment, according to our knowledge, this is the third case of liver abscess which has recovered by on antibiotic rational treatment without surgical punctures. Can we treat the liver abscess like the pneumonia according to features of localization and clinical history? PMID- 8197030 TI - The clinical pharmacology and use of paroxetine, a new selective serotonin reuptake inhibitor. AB - Major depression afflicts a significant percentage of the population, and optimum therapy is often limited by the poor tolerability and lethality in overdose of the tricyclic antidepressants. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and, more recently, paroxetine are viewed as welcome additions to existing therapy. The SSRIs are as effective as the tricyclic antidepressants, but are not associated with their adverse effect profile. Paroxetine in dosages of 20-50 mg/day is as effective as the older classic antidepressants, including amitriptyline, imipramine, and doxepin. It is effective in the elderly and in patients with recurrent, resistant, or severe depression. PMID- 8197031 TI - Evaluation of two opioid-acetaminophen combinations and placebo in postoperative oral surgery pain. AB - STUDY OBJECTIVE: To determine the relative analgesic potency and adverse effect liability of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, and placebo in the treatment of pain following oral surgery. DESIGN: Randomized, double-blind, single-dose, placebo controlled, parallel-group study with self-ratings at 30 minutes and then at hourly intervals from hour 1 to hour 6. SETTING: Private, oral surgery practice sites. PATIENTS: Three hundred twenty-four outpatients with moderate or severe pain after the surgical removal of impacted third molars were selected. One was lost to follow-up and 32 did not need an analgesic; 232 patients had valid efficacy data. INTERVENTIONS: Patients were treated with a single oral dose of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, or placebo when they experienced steady, moderate or severe pain that, in their opinion, required an analgesic. Using a self-rating record, subjects rated their pain and its relief for 6 hours after medicating; estimates of peak and total analgesia were derived from these subjective reports. MEASUREMENTS AND MAIN RESULTS: This study was a valid analgesic assay. Both active treatments were significantly superior to placebo for all measures of analgesic efficacy. The hydrocodone-acetaminophen combination was significantly superior to the codeine-acetaminophen combination for total pain relief and the number of evaluations with 50% relief. Both active treatments manifested an analgesic effect within 30 minutes; the effect persisted for 5 hours for the codeine combination and 6 hours for the hydrocodone combination. Adverse effects were transient, consistent with the pharmacologic profiles of opioids, and none required treatment. CONCLUSIONS: A slight advantage in analgesic efficacy was demonstrated in this single-dose study for the hydrocodone-acetaminophen combination. Repeat-dose studies, however, should be conducted to determine the clinical significance of the difference in analgesic effect of these opioid combinations. PMID- 8197032 TI - Comparison of ampicillin-sulbactam and ticarcillin-clavulanic acid in patients with chronic renal failure: effects of differential pharmacokinetics on serum bactericidal activity. AB - STUDY OBJECTIVES: To evaluate the pharmacodynamic antibacterial activity of ticarcillin-clavulanic acid (T-C) and ampicillin-sulbactam (A-S) combinations against reference bacterial strains in patients with end-stage renal disease maintained on long-term hemodialysis. DESIGN: Randomized, crossover, controlled study. SETTING: National Institutes of Health-funded general clinical research unit in a Veterans Administration Medical Center. PATIENTS: Nine adult men with end-stage renal disease maintained on long-term hemodialysis. Two subjects did not complete the study due to problems of vascular access, and another withdrew for personal reasons. INTERVENTIONS: On a nondialysis day, each subject was randomly administered either T-C 3.1 g or A-S 3 g as a slow intravenous infusion over 30 minutes. Serial blood samples were collected for measurement of antibiotic serum concentrations and determination of serum bactericidal titers. Following a washout period, the study was repeated with the alternative antibiotic combination. MEASUREMENTS AND MAIN RESULTS: The mean observed apparent beta-half-life of clavulanic acid was substantially shorter than that for the other three drugs. The bactericidal activity of both A-S and T-C against non-beta lactamase-producing (N beta-LP) strains of S. aureus and E. coli was consistently high, as indicated by geometric mean SBTs of at least 1:5 at 24 hours. Against beta-lactamase-producing (beta-LP) S. aureus, the geometric mean SBTs for A-S were at least 1:25 throughout the study period, while the geometric mean SBTs for T-C decreased over 24 hours from 1:29 to 1:6. Against beta-LP E. coli, the bactericidal activities for both A-S and T-C were poor, with geometric mean peak SBTs of only 1:6 and 1:3, respectively. The geometric mean SBT for T-C against this E. coli strain had declined to 1:1 at 6 hrs. CONCLUSION: Increasing the dosing interval for T-C in patients with end-stage renal disease may lead to periods of insufficient clavulanic acid to protect ticarcillin from beta lactamase degradation. PMID- 8197034 TI - Symptomatology, pulmonary function and response, and T lymphocyte beta 2 receptors during smoking cessation in patients with chronic obstructive pulmonary disease. AB - STUDY OBJECTIVES: To characterize the effect of smoking cessation and nicotine replacement on pulmonary symptomatology, baseline pulmonary function and response to terbutaline, and purified T lymphocyte beta 2-receptor regulation; and the relationship between T lymphocyte beta 2-receptor density and pulmonary function. DESIGN: Open-label, longitudinal, 28-week study. SETTING: A university clinical research center. PATIENTS: Eighteen long-term smokers with mild to moderate chronic obstructive pulmonary disease (COPD) were enrolled and seven completed the study. INTERVENTIONS: Subjects stopped smoking with the aid of nicotine substitution and behavioral counseling. Pulmonary response (FEV1) to subcutaneous terbutaline and T lymphocyte beta 2-receptor density (Bmax) and function (cAMP) were measured prior to smoking cessation (week 0), during nicotine replacement (week 8), and after nicotine cessation (week 28). MEASUREMENTS AND MAIN RESULTS: Serum cotinine concentrations, plasma epinephrine concentrations, and day and night cough decreased significantly after smoking cessation, whereas basal cAMP concentrations increased (p < 0.05). No significant change was seen in baseline FEV1, pulmonary response to terbutaline, or Bmax over the 28 weeks; however, intrasubject changes in Bmax between visits correlated significantly (p < 0.05) with intrasubject changes in pulmonary response between visits. CONCLUSIONS: Our data indicate that smoking cessation is associated with a significant decrease in the symptomatology of COPD, and that change in T lymphocyte beta 2-receptor density is a good marker of change in pulmonary response to beta 2-agonists. PMID- 8197033 TI - Assessment of the effects of ciprofloxacin and nalidixic acid on cerebral blood flow and metabolism in healthy subjects by positron emission tomography. AB - STUDY OBJECTIVES: The mechanism by which the fluorinated quinolones produce central nervous system effects is unknown. Using positron emission tomography (PET), we evaluated the effects of two quinolones on brain blood flow as well as on oxygen and glucose metabolism. These determinations were done in conjunction with ophthalmologic and neuro-ophthalmologic testing. DESIGN: Randomized, double blind, placebo-controlled, 7-day course of ciprofloxacin 750 mg (C750) or 500 mg (C500) every 12 hours, or nalidixic acid (NA) 1 g every 6 hours. POPULATION: Twenty-four healthy male volunteers, six in each treatment arm. RESULTS: [table: see text] CONCLUSIONS: Compared with baseline values, NA significantly reduced brain glucose uptake, whereas C500, C750, and placebo produced no detectable effect. No compound significantly altered brain blood flow or oxygen metabolism compared with baseline or other treatments. No significant effect on electroretinographic, electro-oculographic, or other neuro-ophthalmologic tests was observed. PMID- 8197035 TI - Evaluation of ketorolac, ibuprofen-paracetamol, and dextropropoxyphene paracetamol in postoperative pain. AB - STUDY OBJECTIVE: To compare the analgesic efficacy of ketorolac, ibuprofen paracetamol (acetaminophen), and dextropropoxyphene-paracetamol in postoperative pain. DESIGN: Randomized, double-blind, parallel, single-dose study. SETTING: Multicenter, with five centers participating. PATIENTS: One hundred sixty patients with moderate to severe postoperative pain requiring oral analgesics were enrolled. Seventeen patients were excluded from final analysis due to deviation from protocol. INTERVENTIONS: Ketorolac tromethamine 10 mg, a combination of ibuprofen 400 mg plus paracetamol 325 mg, or a combination of dextropropoxyphene 65 mg plus paracetamol 400 mg was given orally to patients with moderate to severe baseline pain. MEASUREMENTS AND MAIN RESULTS: Pain intensity and pain relief scores were rated at baseline, at 30 minutes, and hourly to 6 hours. Until the end of first hour, analgesia was similar for all three regimens. Ketorolac had a significantly higher analgesic effect than the two combinations between hours 2 and 6. Analgesia was similar for the two combinations. For all three test drugs the frequency of adverse effects was similar. CONCLUSIONS: Ketorolac 10 mg is a superior analgesic to ibuprofen paracetamol or dextropropoxyphene-paracetamol in the treatment of postoperative pain. PMID- 8197036 TI - Cost-effectiveness of antihypertensive agents in patients with reduced left ventricular function. AB - A pharmacoeconomic primer reviews current economic models used to analyze and synthesize information that may be considered in certain health-related policies or clinical decisions. Heightened budgetary pressures concomitant with mandates for demonstrable increases in efficacy and safety have fostered greater use of cost-effectiveness analyses (CEAs) throughout the health care industry. In the field of hypertension, major clinical trials of pharmacotherapeutic regimens generally demonstrated benefit of reducing blood pressure; CEAs supplied additional data concerning the optimum selection among alternative antihypertensive therapies. As interest has focused on the preservation of left ventricular (LV) function for the best prognosis, it has become increasingly evident that not all antihypertensive regimens affect LV function in the same way. Thus CEA may be an appropriate method to evaluate these effects and facilitate the identification of a regimen that minimizes deterioration of LV function. PMID- 8197038 TI - Correlations of exercise test and quality of life variables with clinical improvement in effort angina. AB - The value of the exercise test has been challenged in connection with assessments of the effects of drugs on angina. Therefore, a series of test variables were correlated with clinical improvement in 30 patients with effort-related angina and coronary stenoses proved by angiography. The patients had two bicycle tests with an interval of 1 year. They were also clinically graded by a combined score of drug consumption and self-assessment of physical fitness on those two occasions, and classified as deteriorated or unchanged, improved, or without symptoms. Sixteen patients had an aortocoronary bypass during the time between the tests. The highest coefficient of correlation was between differences in heart rate at 1 mm ST depression and changes in clinical grading (r = 0.78, p = 0.001). Fairly good correlations were found when changes in total exercise time and changes in maximum double product were related to changes in clinical grading. Differences in maximum ST depression and in blood pressures at 1 mm ST depression did not correlate with clinical improvement; neither did changes in estimates of quality of life. PMID- 8197037 TI - Bactericidal activity of low-dose ceftizoxime plus metronidazole compared with cefoxitin and ampicillin-sulbactam. AB - Eighteen volunteers received ceftizoxime 1 g plus metronidazole 500 mg intravenously every 12 hours, cefoxitin 2 g intravenously every 6 hours, and ampicillin-sulbactam 3 g every 6 hours in a triple-crossover, open-label study to compare serum bactericidal titers (SBTs) against two strains of Escherichia coli and Bacteroides fragilis. Serum was analyzed for drug concentration and bactericidal activity. Ceftizoxime-metronidazole exhibited a significantly greater (p < 0.05) area under the bactericidal curve and percentage of the dosing interval with SBTs of 1:2 or above against E. coli than cefoxitin or ampicillin sulbactam. The respective values were equal to those of ampicillin-sulbactam for one strain of B. fragilis (both greater than cefoxitin) and greater than cefoxitin and ampicillin-sulbactam for the other strain. A 1-g dose of ceftizoxime given with metronidazole 500 mg every 12 hours should be an effective alternative to standard antibiotic treatment of mixed aerobic-anaerobic bacterial infections. PMID- 8197039 TI - Individualizing vancomycin dosing regimens: an evaluation of two pharmacokinetic dosing programs in critically ill patients. AB - We evaluated the predictive performance of two commercial computer programs (Abbott and Simkin) for pharmacokinetic dosing of vancomycin in 50 critically ill patients, 40 with hematologic malignancies and 10 in intensive care. Predictive performance was assessed for both pharmacokinetics and forecasting vancomycin serum levels by using a set of peak and trough drug levels per patient. The effect of renal function and serum sampling (steady state, nonsteady state) on predictive performance of both programs was also analyzed. No statistically significant differences were found between the programs for predicting either pharmacokinetics or serum levels, regardless of a patient's renal function or serum sampling. The Abbott and Simkin programs were similar for individualizing vancomycin dosage regimens. PMID- 8197040 TI - Patient drug attributions and postmarketing surveillance. AB - Although studies have shown that patients can distinguish probable adverse drug reactions (ADRs) from adverse clinical events (ACEs) caused by other factors, it is not known whether these attribution judgments add any independent validity to other accepted methods of identifying ADRs, such as physician assessments or epidemiologic data. Data from 2487 patients receiving fluoxetine and 815 receiving trazodone were used to see whether such information was redundant when added to standard statistical analysis directed toward detecting ADRs. Relative risk values for 14 trazodone or fluoxetine ADRs were selected because each was significantly identified by an innovative postmarketing surveillance system. In one analysis, all patient reports were used to compute relative risk; in the other, only reports attributed by patients to the study drug were included. Results indicate that taking into account patient attribution judgments results in a consistent, albeit modest, increase in the discriminatory power of this monitoring method. PMID- 8197041 TI - Albuterol delivery by metered-dose inhaler with a pediatric mechanical ventilatory circuit model. AB - STUDY OBJECTIVE: To determine albuterol delivery by metered-dose inhaler (MDI) in an in vitro pediatric mechanical ventilatory circuit model. The influence of a spacing device, endotracheal tube (ETT) diameter and length, and air humidity was also investigated. DESIGN: An albuterol MDI canister was connected to an AeroVent spacer or Airlife MDI adapter and ETT 4.0, 5.0, or 6.0 mm at commercially available and equal lengths. The ETT tip was attached to an in-line filter holder with a 1-microns type A/E glass fiber filter. Ventilator settings were fractional concentration of inspired oxygen 50%, tidal volume 250 ml, inspiratory:expiratory (I:E) ratio 1:3, rate 25 breaths/minute, temperature 35 degrees C, and a decelerating flow pattern. Ten albuterol canisters were activated two times each (total 2000 micrograms) into dry (4.0-, 5.0-, and 6.0-mm ETT) and humidified air (4.0- and 6.0-mm ETT) and repeated in triplicate. Percentage MDI output was determined by weighing the filter before and after drug administration (balance sensitivity 10 micrograms). Significant differences (p < or = 0.05) among the groups with and without a spacer and in dry and humidified air were determined by ANOVA with Scheffe's multiple comparison test. Multiple regression was used to determine significant associations between ETT diameter and length and delivery. MAIN RESULTS: With the AeroVent spacer in humidified air, delivery with the 4.0- and 6.0-mm ETT was approximately 2.3% and 5%, respectively. The spacer and dry air significantly improved delivery. CONCLUSIONS: In humidified air, the dose of albuterol by MDI with an AeroVent spacer should be doubled for children intubated with 6.0-mm ETT, and four puffs administered for every one puff desired for 4.0 mm ETT. The results of this investigation should prove useful in initial clinical trials of albuterol MDI in ventilator-dependent infants and children. PMID- 8197042 TI - The effect of short-term administration of theophylline on erythropoietin levels in healthy adults. AB - A previous study demonstrated suppression of erythropoietin production in patients treated with long-term theophylline. This effect could exacerbate anemia of prematurity in neonates receiving this drug for apnea of prematurity. In this pilot project we evaluated the effect of short-term theophylline administration on serum erythropoietin in healthy adults. Six subjects were given a bolus followed by a continuous infusion of theophylline targeted to achieve a serum level of at least 10 micrograms/ml, followed by oral theophylline for 36 hours. Serum erythropoietin and theophylline levels were measured before, during, and after drug infusion. Complete hemograms were performed before and after completion of the infusion. No significant changes in serum erythropoietin levels were seen at any time (F = 1.57, p = 0.12). Hematologic values also remained unaltered. We conclude that short-term administration of theophylline is unlikely to have any effect on serum erythropoietin levels in healthy adults. PMID- 8197043 TI - Application of actigraphy in the clinical setting: use in children with attention deficit hyperactivity disorder. AB - Clinicians rely primarily on subjective behavioral questionnaires in assessing attention-deficit hyperactivity disorder (ADHD). The new mini-motion logger actigraph, which is a wrist-worn minicomputer, can add an objective element to this assessment and is especially useful in children due to its small size. We applied this technology as an outcome measure in evaluating drug therapy in two children with ADHD who were receiving methylphenidate and pemoline, respectively. We also assessed preliminary findings from an additional 13 children. PMID- 8197044 TI - Comparison of PT, aPTT, and factor VII values obtained by concurrent sample collection by direct venipuncture and peripheral venous catheters. AB - STUDY OBJECTIVE: To compare prothrombin time (PT), activated partial thromboplastin time (aPTT), and factor VII values in concurrent blood samples obtained by direct venipuncture and from a peripheral venous catheter. DESIGN: Concurrent samples obtained from catheters and by direct venipuncture were studied. In a separate crossover bioequivalence assessment of DNA-derived factor VIIa (rFVIIa) from two different batches, sample results of each technique were compared. SETTING: University hospital clinical research unit. PATIENTS: Six patients with hemophilia A under nonbleeding conditions. INTERVENTIONS: The patients received a single dose of rFVIIa 70 micrograms/kg administered by intravenous push over 2 minutes. Concurrent blood samples were collected at 2, 3, 4, 6, 8, 10, and 12 hours after rFVIIa administration. Catheter blood samples were drawn from a three-way stopcock attached to an 18-gauge peripheral venous catheter in the patient's forearm and connected to an intravenous solution of 5% dextrose with half normal saline maintained at a rate of 30 ml/hour. Venipuncture samples were drawn from the opposite arm. MEASUREMENTS AND MAIN RESULTS: The PT and aPTT values were determined by using a BBL Fibrometer (PT) and a Coagamate X 2 with automated aPTT reagent. Blood samples were analyzed for factor VII concentration using the Novo Clot assay. The mean venipuncture-obtained PT (8.9 +/- 1.0 sec) and aPTT (48.7 +/- 13.6 sec) values were numerically equivalent to mean catheter-derived PT (9.0 +/- 1.0 sec) and aPTT (48.3 +/- 12.5 sec) results, as were mean venipuncture and catheter-obtained FVII:C values. CONCLUSIONS: The PT and aPTT values determined after venipuncture and through the peripheral catheter were not statistically different (p > 0.05) when compared by paired or unpaired analysis. Similarly, values of FVII:C measured after venipuncture were statistically equivalent to those after sampling through the peripheral catheter. All six patients preferred the catheter method of blood collection over venipuncture. PMID- 8197045 TI - Impact of compliance and side effects on the clinical outcome of patients treated with oral erythromycin. AB - STUDY OBJECTIVE: To determine the relationship among compliance, side effects, and self-reported outcome for patients in an erythromycin trial. DESIGN: A retrospective analysis of data from a multicenter, prospective, single-blind, randomized trial. SETTING: Five metropolitan ambulatory care offices. PATIENTS: The 252 adults (> 18 yrs) were prescribed oral erythromycin 1.0 g/day (base equivalent) for infectious disorders. INTERVENTION: Subjects received erythromycin for 10 days and reported compliance, drug efficacy, and side effects in a daily diary. Compliance was measured by tablet count. RESULTS: A negative correlation was found between gastrointestinal symptom severity score and percentage of tablets taken (p < 0.001). A significant positive correlation was seen between compliance and outcome (p < 0.001). Subjects who took greater than 80% of the drug achieved the treatment goal more frequently than those taking 80% or less (94% vs 59%, p < 0.001). CONCLUSIONS: Side effects of erythromycin adversely affected compliance. Compliance had a positive effect on self-reported outcome. PMID- 8197046 TI - Central nervous system toxicity associated with meperidine use in hepatic disease. AB - Meperidine-associated central nervous system (CNS) excitatory toxicities are believed to be caused by accumulation of the active metabolite normeperidine. Normeperidine is eliminated by the kidneys and accumulates in patients with renal insufficiency, sickle cell disease, and cancer. In patients with cirrhosis, the metabolism of meperidine is decreased, leading to accumulation of the parent drug and possible CNS depressive effects similar to hepatic encephalopathy. Although the elimination of normeperidine is decreased as well in these patients, the ratio of normeperidine to meperidine is generally low, and the narcotic effects of meperidine usually predominate. This is the first reported case of CNS excitatory toxicities in a patient with alcoholic hepatitis and cirrhosis, and normal renal function. Administration of multiple doses of meperidine in patients with hepatic disease should be discouraged. PMID- 8197047 TI - Complete heart block and torsade de pointes associated with thioridazine poisoning. AB - A 72-year-old woman attempted suicide with thioridazine 3000 mg and 60 tablets of acetaminophen 325 mg plus codeine 30 mg. She was semicomatose and had persistent third-degree atrioventricular block, progressive hypotension, and an episode of torsade de pointes. Heart block, arrhythmias, and hypotension resolved within 48 hours, and the patient recovered without adverse sequelae. PMID- 8197048 TI - Cytomegalovirus colitis after 5-fluorouracil and interferon-alpha therapy. AB - Cytomegalovirus (CMV) infection is an opportunistic viral infection primarily affecting immunocompromised patients. Patients with inflammatory bowel disease have an increased risk for developing CMV infections of the gastrointestinal tract. While receiving continuous infusion of 5-fluorouracil and interferon alpha, a 72-year-old woman with stage IV pancreatic carcinoma developed severe colitis with diarrhea that was refractory to conventional antidiarrheals. A biopsy specimen from the colon revealed CMV inclusions, which were confirmed by immunofluorescence. The patient was given ganciclovir 210 mg (5 mg/kg) every 12 hours for 14 days, and the diarrhea resolved after approximately 8 days of therapy. This is the first reported case of CMV colitis associated with combination 5-fluorouracil and interferon-alpha therapy. PMID- 8197049 TI - Empathy to apathy: a consequence of higher education? PMID- 8197050 TI - Secret White House task force documents--shocking! PMID- 8197051 TI - Say no to government control of patient care. AB - Healthcare reform threatens to jeopardize the role of physicians in deciding what is appropriate care for their patients. Factors outside the doctor-patient relationship, such as a global budget and limited access, will exert increasing influence on the decision-making process, according to Dr Dewberry. In this commentary, he explores the roots of this dangerous trend and suggests that physicians take an uncompromising stance against it. PMID- 8197052 TI - Say no to healthcare price controls. AB - Throughout history, price controls on goods and services have never worked. Nevertheless, a number of healthcare reform proposals currently under discussion include price controls as a means of cost containment. Mr Dingman argues that the fundamental structure of the current system should be maintained and that price controls, rather than containing healthcare costs, will actually raise them. PMID- 8197054 TI - What will Congress do to healthcare? A talk with Sen Phil Gramm. Interview by Glen C. Griffin and Amber Stenger. PMID- 8197053 TI - Say no to inadequate tort reform. AB - From his vantage point as president of a large multispecialty group practice. Dr Montgomery has observed the direct effects that medical malpractice liability has had on healthcare costs. Here he offers a counterpoint to the Clinton plan's malpractice provisions and enumerates his own recommendations for meaningful tort reform. PMID- 8197055 TI - How to avoid being dropped from managed care plans. AB - Unexplained, arbitrary termination of doctors from managed care plans is becoming more common in the United States. The action often has substantial financial impact on a medical practice and ends established doctor-patient relationships with very little notice. Can you do anything to minimize your risk of being dropped without cause? Dr Bailey, a plastic surgeon and attorney, offers some tips that may help you avoid a "Dear Doctor" letter. PMID- 8197056 TI - Kaiser Permanente's twist on managed care. A talk with David M. Lawrence, MD. Interview by Amber Stenger. PMID- 8197057 TI - Fix the healthcare system without making it worse. AB - President Clinton's prescription for healthcare reform is a social experiment on an unprecedented scale, according to Dr Kissick. As an alternative, he recommends a more measured approach, with incremental steps toward ensuring universal access to healthcare for all Americans. In this commentary, he points out the potential side effects of current reform proposals and explores fundamental issues for Congress to address. PMID- 8197058 TI - You can't buy insurance when the house is on fire. Community rating kills health insurance. AB - Why does health insurance cost so much? According to the vice president at the insurance company that pioneered high-deductible health insurance to go with medical savings accounts, a big factor is that insurance companies are being asked to solve social problems. Mr Hartnedy offers a solution to America's healthcare-delivery plight that includes empowerment of individuals and preservation of choice. PMID- 8197060 TI - Get off the fence and do something. Interview by Corrinne Charais. PMID- 8197059 TI - Compromise is surrender. AB - Lower standards. Waiting lists. Physician indifference. These are just some of the consequences of national healthcare in Britain, according to the author of this article, a family physician who trained in Scotland. Through a series of extraordinary anecdotes, Dr Anderson comments on Britain's underfunded medical system and the coping mechanisms that doctors rely on to function within it. PMID- 8197061 TI - [Problems in auditory perception and verbal and nonverbal intelligence]. AB - The connection between auditory perception and verbal/nonverbal cognitive achievements were studied in a sample of 300 clients of the school counselling service in the district of Neuss. Nearly 46% of the pupils do have problems with the auditory perception; these pupils do have lower test-results in overall intelligence, especially in verbal cognitive achievements. It is concluded that tests concerning the auditory perception should be used more often. PMID- 8197062 TI - [Systemic approaches in ambulatory child and adolescent psychiatry]. AB - Systemic therapy is considered a method which is based upon the constructivist development of systemic theories. The effectiveness and efficiency thereof is discussed on the basis of one's own evaluation of the therapy with a reflecting team. Further more conceptional differences are determined between the two social systems child psychiatry and systemic therapy. These preliminaries are the foundation upon which we are able to discuss the status of systemic therapy within child psychiatry in theory as well as in practice. PMID- 8197063 TI - [The transference phenomenon in child psychoanalytic therapy]. AB - Transference in analytic child psychotherapy takes place in an extended net of relationships--in contrast to adult analytic psychotherapy. The special features of analytic child psychotherapy are a result, for one, of this extended net of relationships and, for another, of the immaturity of a child's ego development and the varying degree of severity of the psychic illness. It is the purpose of this article to show that these factors play a role in transference--based upon transference as A. Freud understood it--and to demonstrate this with different disorders by briefly recounting several case histories. PMID- 8197064 TI - [Effects of an intensive therapy program for behaviorally disordered mentally handicapped patients on staff personnel in residential care]. AB - This study evaluates the effects of an intensive therapy program designed for mentally handicapped persons with severely disturbed or autistic behavior on their staff personal which had an active role in the program. The staff members rated their professional competence, quality of interaction with the client, team culture and work satisfaction before and after being engaged in the program, with additional ratings of their personal aims at the beginning of the program. Three sets of data were obtained with the program being conducted three times in a row. The testings of the related as well as the independent samples show differentiated program effects. The main effect is an increase of the professional competence and quality of interaction, especially by the qualified staff members. Trainees put emphasis on the development of their personal relationship with the client. The results are discussed in terms of the impact of learning processes specific to the roles of the staff members and motivational factors on learning and therapy outcome, along with institutional conditions influencing successful learning. Thus the program facilitates the professional and interpersonal learning process of staff members in a specific way with success as well as with limitations. PMID- 8197065 TI - [Differences in current state and at the beginning of cancer therapy and possible sequelae: a pilot study in pediatric oncology]. AB - The psycho-social and medical care of families with a cancer sick child can be more effective if the team can identify those parents who need help most desperately from the very beginning. In a retrospective study of 20 patients and their families two groups of parents with different levels of stress could be seperated. Highly stressed parents demonstrated already at the time of diagnosis unfavorable coping strategies with the possibility of a cancer disease. They experience a high degree of guilt feelings and believe that they might be responsible for the occurrence of the disease. However they refuse more often than the other parents psycho-social help offered by the professionals. The results suggest to implement special kind of help for the more stressed families already in the early phase of diagnosis and treatment. PMID- 8197066 TI - [Molecular genetic detection of t(11;22)(q24;12) translocation in Ewing sarcoma and malignant peripheral neuroectodermal tumors]. AB - Ewing's sarcomas and malignant peripheral neuroectodermal tumors (MPNTs) show very little evidence of differentiation and lack characteristic morphological features at the light-microscopic level. These malignancies have always presented a significant differential diagnostic challenge to the pathologist. Electron microscopy, immunohistochemical staining for neural antigens such as neuron specific enolase (NSE), Leu 7, synaptophysin and, more recently, the detection of Mic-2 gene expression have been included in the routine histopathological diagnostic procedure. However, the expression of these antigens is not restricted to this entity. Thus, further modalities are required to prove diagnostic reliability. One consistent feature of the Ewing's sarcoma family is the presence of the reciprocal chromosomal t(11;22)(q24;q12) translocation. Recent cloning of the t(11;22) break point has led to the identification of the genes involved in this translocation. This provides the possibility of molecular genetic detection of the t(11;22) translocation in Ewing's sarcomas and MPNTs. We have established a method using reverse transcription and the polymerase chain reaction (RT-PCR) for the detection of the specific gene fusion transcript caused by the 11;22 translocation. The validity of our approach was proved by analyzing Ewing's tumor cell lines and tissue material obtained from primary biopsies and tumor resections. Molecular genetic detection of the 11;22 translocation by RT-PCR analysis should perhaps be included in the diagnostic work-up of suspected Ewing's sarcoma and MPNT. PMID- 8197067 TI - [Hypervariable regions (HVR) as genetic markers in tumor diagnosis. Methodological principles and their use in pathologic diagnosis]. AB - Variable number tandem repeats (VNTR) are highly polymorphic DNA sequences which can be used as genetic markers in different fields of medicine. In this report, we describe the methodology of VNTR in diagnostic molecular pathology, using a rapid, DNA-based approach involving polymerase chain reaction (PCR) amplification and electrophoresis of highly polymorphic DNA satellite sequences. As concrete examples of the application of this approach, we present two case reports: 1. A B cell lymphoma of the porta hepatis developed in a 54-year-old man 4.5 months after orthotopic liver transplantation for liver failure due to chronic hepatitis C infection. Using DNA polymorphisms as genetic markers, we showed that the tumor was of donor origin. This finding may be important for the patient's subsequent management. 2. An immature teratoma of the left ovary was found during delivery by cesarean section in a 27-year-old woman. The female newborn survived for 9 weeks and then died from central dysregulation because of an intracranial immature teratoma. Because the synchronous tumors were of similar histology, clonal origin in maternal tissues and metastatic spread were initially suspected. Analysis of highly polymorphic DNA markers clearly indicated that the teratoma carried by the child was of independent genetic origin from the mother's tumor. PMID- 8197068 TI - [Unilateral testicular tumor in adrenogenital syndrome]. AB - In male patients with congenital adrenogenital syndrome (AGS), in addition to the well known adrenal changes, tumor-like testicular proliferations may be observed. They have been known from literature since decades, but have become rare due to modern therapy. Especially in the mild and inapparent cases of AGS, the "tumors" cause clinical and morphological problems. The case of a 34 year old male AGS patient is presented, who underwent resection of a large adrenal cortical adenoma at age 28. Six years later, orchiectomy followed because of a testicular tumor. In frozen sections, the "Leydig cell-like" tumor caused diagnostic difficulties. After usual embedding and examination, the diagnosis of testicular "tumor" in AGS was confirmed. By review of the literature, pathomorphogenesis and morphology of these testicular tumors as well as possible histogenesis of their cells are discussed. Because of the close similarity to Leydig cell tumors, this most important differential diagnosis is especially considered. As a rule, testicular tumors in AGS are no indication for orchiectomy. PMID- 8197069 TI - [Primary primitive neuroectodermal tumor of the kidney in an adult. Clinico pathologic and immunohistochemical case report]. AB - We report a case of a primary renal primitive neuroectodermal tumour in a 24-year old man associated with multiple pulmonary metastases. Histologically, the bulk of the kidney was replaced by a small round-cell tumour with numerous true Homer Wright rosettes and perivascular pseudorosettes; wide-spread vascular invasion was noted. There was no evidence at autopsy of a primary tumour elsewhere. Immunohistochemically, the tumour cells stained strongly positive for O-13, a monoclonal antibody, which recognizes a recently described cell membrane glycoprotein (p30/32MIC2), more weakly for NSE and at least focally for PGP 9.5; the tumour did not stain for other neural markers, cytokeratin, leucocyte common antigen, or desmin. The differential diagnosis of small round-cell tumours in this location and the relation of primitive neuroectodermal tumours and Ewing's sarcoma are discussed. PMID- 8197071 TI - [Quantitative and qualitative molecular biology procedures for analysis of genetic material]. PMID- 8197070 TI - [Malignant lymphoma and colon carcinoma 3 years after heart transplantation and immunosuppression]. AB - Three years after heart transplantation and immunosuppressive therapy, a 66-year old man suffered from dyspnea and showed symptoms mainly due to right heart failure. Malignant tumor cells were discovered within extensive pleural effusion. Computed tomography revealed two lesions of the liver suspicious of metastases, and recurrent blood in the stools was evident. The patient deteriorated rapidly and died 3 weeks after admission. Autopsy findings included an adenocarcinoma of the cecum (grade II) with metastases to the liver. High-grade immunoblastic non Hodgkin's lymphoma of plasmoblastic differentiation was diagnosed, located within the mediastinal soft tissues and infiltrating the peri- and myocardium. Mesenteric lymph nodes were enlarged with histological verification of malignant lymphoma. The lymphatic tumor masses had caused considerable compression of the heart and vessels, leading to the signs of cardiac failure. The development of metastasizing colonic carcinoma and high-grade immunoblastic non-Hodgkin's lymphoma 3 years after heart transplantation and immunosuppressive therapy must be considered an unusual combination. Malignent lymphomas following heart transplantation have been described several times. PMID- 8197072 TI - [Analysis by flow cytometry and cell sorting. Report of current status and perspectives for pathology]. AB - Although flow cytometry was initially used just to count cells, it has developed into a method of measuring the physical and chemical properties of individual cells when they are detected in a fluid stream by electronic sensors. With the application of fluorescence molecules, especially fluorescence-conjugated antibodies that are excited by focused laser light, the spectrum of application has expanded and has for years exceeded the traditional field of hematology. The article presents applications for pathology with the main focus on oncological problems such as DNA multiparameter analysis and proliferation assessment. In addition, the basic aspects of the different types of user-friendly flow cytometers are explained here. PMID- 8197073 TI - [Determination of clonality in lymphoproliferative diseases using polymerase chain reaction]. AB - The diagnosis of lymph node lesions frequently requires the employment of additional studies. Lineage and clonality can be regarded as the most crucial diagnostic parameters. In some cases the diagnosis remains ambiguous even after immunohistochemistry and molecular biologic techniques have to be applied. These molecular biologic techniques are based on specific rearrangements of the immune genes that occur during T- and B-cell development. Whereas Southern blotting has become a standardized and reliable means for the detection of lineage and clonality, the limited availability of fresh frozen material frequently restricts its clinical applicability. The polymerase chain reaction has facilitated the investigation of immune gene rearrangements in formalin-fixed and paraffin embedded tissue samples. This communication reviews the recent developments in this field. PMID- 8197074 TI - [Rational antibacterial chemotherapy of spontaneously acquired pneumonia]. PMID- 8197075 TI - [Lung function reference values for students 6 to 16 years of age]. AB - The diagnosis of lung function impairments in childhood is based on a variety of reference values. The assessment of "normal" function and growth of lung and airways in pediatric and environmental investigations is biased. The detection of small airway disease at an early stage is based on flow volume measurements, however, reference values in Europe relied on small and highly selected groups of children. We examined 18,106 children and adolescents aged 6 to 16 years at their schools by standardized methods. After exclusion of children with poor cooperation, respiratory signs or symptoms and active smokers, regression analysis was applied for FVC, FEV1, PEF, MEF75, MEF50, MEF25, and MMEF predicted from standing height, sex, age and weight. Means and standard deviations (SD) of lung function parameters of healthy Austrian school children are presented as a basis for reference. Individual lung function can thus be evaluated in SD-scores. Flow measures representing small airway functions were found higher in adolescent girls. MEF25 showed the highest variability unexplained by anthropometric characteristics. The new reference values improve available tools for early detection of respiratory diseases and dysfunctions in children and adolescents and they should help to evaluate environmental and other factors influencing function and growth of lung and airways. PMID- 8197076 TI - [Current possibilities and limits of bronchoscopic tracheobronchial stenting]. PMID- 8197077 TI - [Analysis of causes of incorrect use of dose aerosols]. AB - Preparations administered by inhalation make relatively high demands on the skill and knowledge of the patient in handling this form of application, for the effectivity of the therapy is inseparably linked to its faultless application. The present article aims at analysing possible mistakes in handling and at finding the most effective way of avoiding them. Several groups of patients with different previous knowledge were analysed in respect of handling skill and the influence of training on an improvement of the same; the patients' self assessment was analysed by questioning them. Most mistakes are committed by patients whose only information consists of the contents of the package circular. Written instructions alone cannot convey sufficient information especially on how to synchronize the release operations. Major mistakes are insufficient expiration before application in 85.6% of the patients and lack of synchronisation in 55.9%, while the lowest rate of errors in respect of handling was seen in patients who had undergone training and instruction. Training in application associated with demonstration and subsequent exercise reduces the error ratio to a tolerable level. Pulverizers free from propelling gas and preparations applied by means of a spacer are clearly superior to others in respect of a comparatively low error rate. 99.3% of all patients believe they are correctly following the instructions, but on going into the question more deeply it becomes apparent that 37.1% of them make incorrect statements. Hence, practical training in application should get top priority in the treatment of obstructive diseases of the airways. The individual steps of inhalation technique must be explained in detail and demonstrated by means of a placebo dosage aerosol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8197078 TI - [Toxic lung damage caused by mitomycin C]. AB - Lung toxicity is one of the rare side effects of mitomycin C (MMC), an effective antineoplastic agent. There have been only few reports on pulmonary damage after MMC monotherapy. We describe a case of a pulmonary reaction following MMC monotherapy. The patient was examined including bronchoalveolar lavage (BAL) and transbronchial lung biopsy. BAL yielded the diagnosis of a lymphocyte alveolitis with normal CD4/CD8 ratio within the T lymphocytes. Histologically a florid alveolitis was diagnosed. Radiological and CT findings including HR-CT are described. PMID- 8197079 TI - [Reference controlled, randomized double-blind study of the effectiveness of salbutamol/DNCG DA combination in bronchial hyperreactivity in comparison with salbutamol DA alone (parallel group comparison)]. PMID- 8197081 TI - [Phospholipid spectrum of blood serum and erythrocyte membranes in patients with diabetes mellitus and effect of antioxidants on these parameters]. PMID- 8197080 TI - [Immunologic shifts in inhabitants of the Tian'-Shan' lowlands and highlands, suffering from obesity and non-insulin-dependent diabetes mellitus]. AB - Cellular nonspecific immunity was found reduced in residents of the lowlands and highlands suffering from alimentary obesity and noninsulin-dependent diabetes mellitus (NIDM), this depression augmenting with the increment of obesity degree and age of NIDM patients (p < 0.01-0.001). Activities of antihypoxic enzymes in these patients are drastically depressed under conditions of the highlands and do not depend on the patient's age. Lymphocyte killer activity in both patient populations is increased, more so in the highlands; this activity functionally or organically impairs insulin in the body forming with it immune complexes. PMID- 8197082 TI - [Lipid peroxidation in purulent wound tissues in patients with diabetes mellitus]. PMID- 8197083 TI - [Autoantibodies to glutamate decarboxylase in children with newly detected insulin-dependent diabetes mellitus]. AB - Glutamic acid decarboxylase (GAD) is considered as target antigen in pancreatic beta cell autoimmunity. Two isoforms of GAD (islet and brain GAD) were detected recently. In circulation of approximately 80% of recently detected patients with insulin-dependent diabetes mellitus (IDDM) autoantibodies to brain GAD (bGAD) have been demonstrated. To detect autoantibodies to bGAD blood sera of 48 children aged 1 to 14, 36 of these with newly diagnosed IDDM, 2 with impaired glucose tolerance (IGT), 10 healthy controls, were tested. Indirect immunofluorescent staining of rat cerebellum cryoslices was carried out. The results were assessed using fluorescent microscopy and processed by statistical methods. Autoantibodies to bGAD were found in 30 out of 36 patients with IDDM: 83.3 +/- 12.4% (p = 95%), in 1 with IGT, and in none of controls. The fact that all controls were antibody-negative proves a high specificity of this immunological marker of IDDM. Family history or a younger age by the moment of diabetes onset were conductive to a higher prevalence of autoantibodies to GAD, each of these factors being unrelated to the other. PMID- 8197084 TI - [Effect of soybean protein isolate on energy substrate oxidation in patients with insulin-dependent diabetes mellitus]. AB - Using indirect colorimetry, the authors demonstrated disordered energy metabolism at rest in patients with insulin-dependent diabetes mellitus (IDDM) with a moderate decompensation of metabolism: carbohydrate oxidation was reduced and fat and protein oxidation increased, this being aimed at maintenance of the basic metabolism within the normal range under conditions of insulin insufficiency. Improvement of common parameters of compensation during optimization of insulin therapy and therapeutic diets was associated with approximation of substrate oxidation structure and energetic structure of a diet, as well as with increased production of useful energy coupled with reduced oxygen consumption. Moreover, a positive correlation between insulin level and carbohydrate oxidation rate was revealed. Analysis of the effects of qualitative composition of protein showed a more rapid improvement of metabolism during metabolic diet, whereas during therapy with diets including soybean protein increase of metabolism efficacy is more manifest. Bioenergetic parameters may be used as criteria of the efficacy of IDDM treatment. Changes in these parameters not always correlate with the time course of routine criteria of compensation and provide supplementary information on a patient's metabolic status. PMID- 8197085 TI - [Efficacy of repeated courses of hyperbaric oxygenation in treatment of insulin dependent diabetes mellitus]. AB - Repeated courses of hyperbaric oxygenation (HBO) were administered to 39 patients with insulin-dependent diabetes mellitus (IDDM) aged 28.2 +/- 11.3 years on an average and mean diabetes duration 5.7 +/- 0.5 years without body mass excess, administered insulin in daily dose 35.5 +/- 10.1. Control group consisted of 8 IDDM patients matched for clinical parameters and administered no treatment. Daily glucosuria, glycemia, HbA1, blood levels of e-peptide, glucagon, STH, and hydrocortisone were measured in the test group and controls before and after HBO course and every 2 months of a years's follow-up. Repeated courses of HBO administered to IDDM patients during a year are much more effective than a single course as regards diabetes compensation, reduction of insulin consumption, recovery of residual insulin secretion, and suppression of secretion of contrinsular hormones glucagon, STH, and hydrocortisone. Three courses of HBO therapy administered to IDDM patients at 4 months intervals are more effective than two courses with a 6 month interval; at the same time, in a three course modality the maximal positive effect of HBO on the hormonal metabolic status is attained during the second course, and the third course just fortifies the attained effect. PMID- 8197086 TI - [Optimal frequency of hyperbaric oxygenation courses in non-insulin-dependent diabetes mellitus]. AB - Repeated courses of hyperbaric oxygenation (HBO) in patients with noninsulin dependent diabetes mellitus (NIDDM) are much more effective than a single course as regards their favorable influence on carbohydrate metabolism and hormonal and metabolic parameters (recovery of residual insulin secretion and suppression of secretion of contra-insulin hormones). Three courses of HBO administered to NIDDM patients at 4 months intervals are more effective than two courses at 6 months interval; at the same time during a three-course modality the maximal favorable HBO effect on the hormonal and metabolic status is attained after the second course, and the third one only fortifies the attained favorable effect. PMID- 8197087 TI - [Mortality in children with diabetes mellitus in Moscow]. AB - Analysis of the mortality of children with insulin-dependent diabetes in Moscow in the eighties revealed a very high specific incidence of diabetic ketoacidosis, the principal cause of lethal outcomes occurring in the period of the disease manifestation in more than a half of the analyzed cases. Mortality index among children with diabetes was found higher than in countries with well-developed economy. The overwhelming majority of untimely lethal outcomes of diabetes mellitus in childhood may be prevented. PMID- 8197088 TI - [Morphology of the thyroid tissue in multinodular euthyroid goiter]. PMID- 8197089 TI - [Blood serum immunoglobulins from patients with juvenile struma reduce the cAMP level in isolated human thyrocytes]. AB - Clinico-hormonal examinations of 19 patients with juvenile struma revealed in many of them signs of latent hypothyrosis (increased age-specific level of blood serum TTH level and hyperergic reaction to TRH). Incubation of thyrocytes isolated from perinodular tissue of patients with euthyroid nodular goiter with IgG isolated from the blood serum of patients with juvenile struma resulted in a reliably lower content of cAMP in the cells than after thyrocyte incubation with IgG isolated from the blood serum of 9 healthy donors. This is indicative of the presence of thyroblocking antibodies in the blood serum of patients with juvenile struma. Though no correlation could be traced between the tested immunoglobulin activity, on the one hand, and blood serum TTH level and struma size, on the other, one may propose a contribution of thyroblocking antibodies to the pathogenesis of juvenile struma. PMID- 8197090 TI - [Endocrinologic aspects of monitoring and medical rehabilitation of the population in controlled regions contaminated after the Chernobyl nuclear power plant accident]. PMID- 8197091 TI - [Cytogenetic activity of testosterone propionate and methyltestosterone in a culture of lymphocytes of healthy women and women suffering from hyperandrogenism]. AB - To discover the effects of various concentrations of androgenic preparations on lymphocyte cultures from healthy women (group 1) and of women with hyperandrogenism (group 2), a total of 6792 metaphases were examined after peripheral blood lymphocyte culturing after Hangerford. The data indicated a relatively high incidence of aberrant metaphases, total number of ruptures and paired ruptures in the second group, a higher cytogenetic activity of testosterone propionate in both groups, and a higher cytogenetic activity of androgenic hormones in the second group. Bearing in mind a similar, if not higher, activity of endogenic testosterone in a female organism, we must admit a high probability of genetic system involvement in women suffering from hyperandrogenism. PMID- 8197092 TI - [Clinical variants of McCune-Albright-Braitsev syndrome in girls]. AB - The authors analyze published data on clinical variants and hormonal parameters in patients with this syndrome and present their own observations of children with this condition. Besides early sexual maturation, they describe the clinical picture of Cushing's syndrome, thyroid nodular hyperplasia. The said disorders do not depend on the tropic effect of the hypothalamohypophyseal system. A hypothesis is put forward about primary activation of adenylate cyclase system in the origin of the disease. PMID- 8197093 TI - [Surgery of pituitary microadenoma, complications and treatment]. AB - The authors analyze their observations of 118 patients with hypophyseal microadenomas in 1990-1992. Forty-four patients had prolactinomas, 35 somatotropinomas, 29 corticotropinomas, and 10 mixed tumors of the hypophysis. Operative interventions via a transseptal approach developed by the authors were carried out in all the patients. Complications of such operations are analyzed and methods of their treatment presented. The results lead the authors to a conclusion that selective microsurgery should be a method of choice in the treatment of hypophyseal microadenomas. PMID- 8197094 TI - [Clinico-cytogenetic examination of a patient with karyotype 46,XX, azoospermia and sterility]. PMID- 8197095 TI - [A giant neurinoma with hypoglycemic syndrome]. PMID- 8197096 TI - [Training of patients as an integral part of treatment of type I diabetes mellitus: history of the development, principles, assessment of efficacy]. PMID- 8197097 TI - [Development of the reproductive system in the progeny of rats with streptozotocin diabetes]. AB - Specificities of functioning and development of the reproductive system and mechanism of its regulation with hypothalamic structures were studied in the progeny of rats with streptozotocin diabetes. For this purpose pituitary sensitivity was analyzed in mature animals, as was functional capacity of the feedback system mediating the hypothalamic regulation of gonadotropin secretion in rat males and females at the age when this system normally starts functioning in health. The hypothalamo-hypophyseo-gonadal system feedback mechanism was found to develop in the progeny of female rats with streptozotocin diabetes later than in health. Pituitary sensitivity to LH-RH was reduced and LH level reduced by 1.5 times in mature progeny of rats with streptozotocin diabetes as compared to that in the progeny of healthy rats. These results permit a conclusion that the progeny of rats with streptozotocin diabetes develop disorders in the mechanism regulating the reproductive system of the body, though not so grave as to make this system functioning impossible. PMID- 8197098 TI - [Growth in the pubertal period in genetic disorders of sex hormone action and secretion]. PMID- 8197099 TI - [Growth hormone therapy in Turner's syndrome: analysis of the effect of therapy on the final height]. PMID- 8197100 TI - [Review of studies on growth hormone receptor insufficiency (Larone's syndrome)]. PMID- 8197101 TI - [Clinical and biochemical characteristics of growth hormone receptor insufficiency (Larone's syndrome)]. PMID- 8197102 TI - [Therapy with recombinant human insulin-like growth factor I in children with growth hormone receptor insufficiency (Larone's syndrome)]. PMID- 8197103 TI - [Incidence of craniopharyngioma relapses in children treated with growth hormone]. PMID- 8197104 TI - [Immunologic aspects of renal involvement in patients with type II diabetes mellitus]. AB - Besides the known factors contributing to the pathogenesis of diabetic nephropathy, the role of immune mechanisms in types I and II diabetes is discussed of late; the contribution of autoimmune mechanisms to pathogenesis of noninsulin-dependent diabetes (NIDDM) is virtually unknown. Seventy-six patients with NIDDM and 48 with insulin-dependent condition were examined. Under study were levels of antibodies to FxIA and renal glomerular basal membrane antigens in the blood sera of donors and patients with types I and II diabetes, as well as concentrations, size, and pathogenicity of immune complexes. Antibodies to FxIA antigen were detected in patients with both types of diabetes with diabetic nephropathy. Detection of circulating antibodies to FxIA antigen in more than 70% of diabetics in the absence of protein in the urine may be used as a test system for the laboratory diagnosis of diabetic nephropathy prestage and as a criterion for prescription as early as at the initial stages of nephroprotective agents. PMID- 8197105 TI - Inherited prion diseases. PMID- 8197107 TI - Microcin B17: posttranslational modifications and their biological implications. PMID- 8197106 TI - A nuclear function for RNase MRP. PMID- 8197108 TI - Regulated vesicular fusion in neurons: snapping together the details. AB - In the past year major strides have been made toward our understanding of the molecular mechanisms involved in regulated vesicle fusion and exocytosis in neurons and neuroendocrine cells. Much of this advance has come from the identification of proteins participating in these events and of their potential roles mediated by interactions with each other, the constituent membranes, and, in some cases, Ca2+ signaling. The involvement of vesicle fusion in elongation of neuronal processes during development and release of transmitters and neuromodulatory peptides in the mature nervous system indicates, however, that refinements in the fusion machinery may be required for each of these acts. For many of the participants in synaptic membrane fusion, variant isoforms have been identified that exhibit modifications that might alter interactive properties of these proteins. We discuss the idea that diversification of isoforms, as illustrated by the expression of alternatively spliced variants of SNAP-25, is likely to be an important component in providing the detail necessary to differentiate the physiology of regulated fusion of different classes of vesicles employed in development, neurotransmission, and secretion. PMID- 8197109 TI - Rapid and accurate estimates of statistical significance for sequence data base searches. AB - A central question in sequence comparison is the statistical significance of an observed similarity. For local alignment containing gaps to optimize sequence similarity this problem has so far not been solved mathematically. Using as a basis the Chen-Stein theory of Poisson approximation, we present a practical method to approximate the probability that a local alignment score is a result of chance alone. For a set of similarity scores and gap penalties only one simulation of random alignments needs to be calculated to derive the key information allowing us to estimate the significance of any alignment calculated under this setting. We present applications to data base searching and the analysis of pairwise and self-comparisons of proteins. PMID- 8197110 TI - Herpes simplex virus DNA replication: a spacer sequence directs the ATP-dependent formation of a nucleoprotein complex at oriS. AB - The origin-binding protein (OBP) from herpes simplex virus 1 is a member of the SF2 helicase superfamily and is required for the initiation of DNA synthesis from a viral origin of DNA replication (oriS). The high-affinity binding sites for OBP in oriS, boxes I and II, are separated by an A+T-rich spacer. We used the gel retardation technique to examine the influence of this spacer sequence on the formation of a specific complex, referred to as complex II, between OBP and oriS. The formation of this OBP-oriS complex was greatly promoted by adenosine 5' [gamma-thio]triphosphate and other nucleotide cofactors. Surprisingly, oriS constructs where the spacer sequence had been altered with approximately half of a helical turn (+4 or -6 base pairs) supported the formation of a more stable complex II than the wild-type origin. DNase I footprinting experiments showed that the cooperative binding of OBP to boxes I and II was affected by the length of the spacer sequence in the same way. In contrast, the ability of oriS containing plasmids to replicate was most efficient with wild-type oriS. This paradox can be resolved if it is assumed that an ATP-dependent cooperative binding of OBP to properly spaced recognition sequences in oriS is required to induce a conformational change of DNA, thereby facilitating initiation of DNA replication. PMID- 8197111 TI - Cellular transformation by a transmembrane peptide: structural requirements for the bovine papillomavirus E5 oncoprotein. AB - The E5 oncoprotein of bovine papillomavirus, only 44 amino acids long, occurs as a disulfide-bonded transmembrane dimer. This remarkable oncoprotein stimulates signal transduction through activation of the platelet-derived growth factor (PDGF) receptor, and E5 exhibits limited amino acid sequence similarity with PDGF. Results presented here suggest that a key feature of the hydrophobic transmembrane domain is an amino acid side chain that participates in interhelical hydrogen bond formation. These data are reminiscent of the activated neu oncogene, in which a point mutation in the transmembrane domain leads to ligand-independent dimerization and activation of a receptor tyrosine kinase. Significantly, the transmembrane domain of E5 can be largely replaced by the transmembrane domain from the activated neu receptor tyrosine kinase. Extensive mutagenesis defines the minimal structural features required for transformation by the E5 oncoprotein as, first, the ability to dimerize and, second, presentation of a negatively charged residue at the extracellular side of the membrane. The biological activity of E5 mutants that lack most amino acid residues similar to PDGF suggests that E5 and PDGF activate the PDGF receptor by distinct mechanisms. PMID- 8197112 TI - TraI, a LuxI homologue, is responsible for production of conjugation factor, the Ti plasmid N-acylhomoserine lactone autoinducer. AB - Conjugal transfer of the nopaline-type Agrobacterium Ti plasmid pTiC58 is regulated by a transcriptional activator, TraR, and a diffusible signal molecule, conjugation factor (CF). CF is a member of a family of substituted homoserine lactones (HSLs) that act as coinducers for regulating gene expression in diverse Gram-negative bacteria by a mechanism called autoinduction. In Vibrio fischeri HSL production is conferred by the luxI gene. Homologues of this gene are responsible for HSL production by other Gram-negative bacteria. A gene that we call traI, conferring production of material with CF activity, was localized to a 1-kb region at the upstream end of tra3 of pTiC58. Spectroscopy showed that the activity was authentic CF. Sequence analysis showed that traI could encode a protein of 211 amino acids, TraI, that is related to the proteins responsible for HSL production by other bacteria. A second, partial open reading frame immediately downstream of traI could encode a protein related to TrbB of plasmid RP4, which is required for conjugal transfer. Transcription of traI and of the downstream tra3 genes requires TraR and CF and initiates from the traI promoter. The results show that traI is responsible for CF production, that it is the first gene of the tra3 operon, and that expression of this operon is regulated by autoinduction. PMID- 8197113 TI - Ras signaling in the activation of glucose transport by insulin. AB - An approach involving microinjection and microanalysis has been developed to investigate signal-transduction pathways involved in the hormonal control of metabolism. We have applied this strategy to investigate the role of Ras signaling in the acute activation of glucose transport by insulin in cardiac myocytes. Glucose transport activity was assessed by measuring the initial rate of accumulation of 2-deoxyglucose 6-phosphate (dGlc6P) in individual cells after incubation in 2-deoxyglucose. Insulin increased accumulation of dGlc6P by 3- to 4 fold, consistent with its stimulatory effect on glucose transport. Accumulation of dGlc6P was increased severalfold by microinjecting the nonhydrolyzable GTP analogue, guanosine 5'-[gamma-thio]triphosphate, which activates members of the Ras superfamily of GTP-binding proteins. Injecting activated Ha-Ras protein also mimicked insulin by increasing dGlc6P; whereas, injecting a Ras protein lacking the COOH-terminal site of fatty acylation required for Ras function was without effect. Introducing the neutralizing Ras antibody Y13-259 into cells attenuated the effect of insulin. These findings implicate Ras in the acute regulation of metabolism by insulin. PMID- 8197114 TI - Adipocyte differentiation selectively represses the serum inducibility of c-jun and junB by reversible transcription-dependent mechanisms. AB - Nonterminally differentiated 3T3 T adipocytes are resistant to growth stimulation by 10% (vol/vol) fetal bovine serum even though they can be induced to proliferate with extremely high serum concentrations. We now report that in adipocytes 10% fetal bovine serum also fails to typically induce c-jun or junB. Rather, after 10% fetal bovine serum treatment, c-jun and junB expression is markedly repressed after a brief initial slight induction. Gel mobility shift studies confirm that AP-1 DNA binding activity is inhibited in adipocytes. Repression in c-jun and junB inducibility in adipocytes results from transcriptional mechanisms, can be reversed by treatment with protein synthesis inhibitors or higher serum concentrations, and does not affect c-fos or c-myc expression. These data suggest that adipocyte differentiation selectively and transcriptionally represses the inducibility of c-jun and junB so as to decrease the cell's ability to proliferate in response to 10% fetal bovine serum. PMID- 8197115 TI - Single-strand conformation polymorphism analysis coupled with stratified DNA sequencing reveals reduced sequence variation in the su(s) and su(wa) regions of the Drosophila melanogaster X chromosome. AB - Single-strand conformation polymorphism (SSCP) analysis followed by DNA sequencing of stratified sub-samples was used to survey DNA polymorphism in the su(s) and su(wa) regions in a natural population of Drosophila melanogaster. su(s) and su(wa) are located near the telomere of the X chromosome, where the rate of crossing over per kilobase of DNA monotonically decreases toward the tip. SSCP was assessed in 12 noncoding segments amplified from the su(s) region (3213 bp) and in 8 noncoding segments amplified from the su(wa) region (1955 bp). Sets of segments were multiplexed in a single electrophoretic lane to increase the number of base pairs assayed per lane. Eight segments were monomorphic, and the other 12 segments exhibited two to four SSCP classes. Only four within-SSCP-class DNA sequence differences (a single nucleotide substitution) were observed among 24,360 bp compared within classes. The between-SSCP-class DNA sequence comparisons revealed 27 substitutions and 9 insertion/deletion polymorphisms. The average numbers of substitutional differences per site were 0.0010 and 0.0021 for su(s) and su(wa), respectively. These values are intermediate between those reported for the more distal y-ASC region (0.0004) and the more proximal Pgd locus (0.0024). This observation is consistent with the prediction of the hitchhiking-effect model-i.e., a monotonic increase in polymorphism as a function of crossing over per kilobase. PMID- 8197116 TI - The expression of nifA in Azorhizobium caulinodans requires a gene product homologous to Escherichia coli HF-I, an RNA-binding protein involved in the replication of phage Q beta RNA. AB - We report the characterization of a mutant of Azorhizobium caulinodans, isolated after ethyl methanesulfonate mutagenesis. This Nod+ Nif- Fix- mutant is unable to synthesize 10 of 15 polypeptides normally induced under conditions of nitrogen fixation. By using lacZ fusions it was shown that nifA and nifA-regulated genes were not expressed in this strain. The mutation was complemented by a constitutively expressed nifA gene or by a 1.1-kb DNA fragment from the wild-type strain, whose nucleotide sequence revealed a single open reading frame of 255 bp coding for an 85-amino acid polypeptide. The deduced amino acid sequence is similar to that of HF-I, an RNA-binding protein of Escherichia coli, which is required for replication of bacteriophage Q beta RNA. The similarity can be extended to the function since hfq, the structural gene for HF-I, complemented the A. caulinodans mutant. The corresponding gene in A. caulinodans was termed nrfA (for nif regulatory factor). Inactivation of nrfA in the mutant was due to a missense mutation resulting in the replacement of a cysteine residue by arginine. A null mutant, constructed by disruption of nrfA, exhibited the same phenotype as the missense mutant. Thus, an additional factor can be added to the already complex system of nifA regulation in A. caulinodans. PMID- 8197117 TI - Neurotensin is an autocrine trophic factor stimulated by androgen withdrawal in human prostate cancer. AB - After therapeutic hormone deprivation, prostate cancer cells often develop androgen-insensitive growth through mechanisms thus far undefined. Neuropeptides have been previously implicated as growth factors in some prostate cancers. Here, we demonstrate that androgen-sensitive LNCaP human prostate cancer cells produce and secrete neurotensin following androgen withdrawal. We show that while LNCaP cells express the neurotensin receptor, only androgen-deprived cells exhibit a growth response to exogenous neurotensin. We further demonstrate that androgen stimulated cells may be refractory to exogenous neurotensin due to androgen induction of a metalloprotease active toward neurotensin. Thus, prostate cancer cells deprived of androgen develop an alternative autocrine growth mechanism involving neurotensin. PMID- 8197118 TI - Fluid shear stress induces a biphasic response of human monocyte chemotactic protein 1 gene expression in vascular endothelium. AB - The focal distribution of atherosclerotic lesions in the arterial tree is related to the local shear stress generated by blood flow, but the molecular basis of the atherogenic response of endothelial cells in these lesion-prone areas is still unclear. We report that shear stress mediates a biphasic response of monocyte chemotactic protein 1 (MCP-1) gene expression in vascular endothelial cells (EC). Northern blot analysis indicated that the level of MCP-1 mRNA in human umbilical vein EC (HUVEC) subjected to a shear stress of 16 dynes/cm2 (1 dyne = 10 microN) for 1.5 hr increased by 2- to 3-fold when compared with static cells. The MCP-1 gene expression decreased to the basal level at 4 hr and then declined further to become completely quiescent at 5 hr after the onset of shear. Once the gene expression was fully suppressed, it remained quiescent even after static incubation for 1.5 hr and would not respond to reshearing after this static incubation. However, if the postshearing incubation extended from 1.5 to 24 hr, the MCP-1 mRNA returned to the basal level and was then able to increase after the reapplication of shear stress. Nuclear run-on experiments showed that the shear-induced increased MCP-1 mRNA in HUVEC was regulated at the transcriptional level. By using cycloheximide, it was shown that de novo protein synthesis was not necessary for the induction of MCP-1 by shear stress. The biphasic response of MCP-1 gene expression was found in experiments in which the applied shear stress was 6, 16, or 32 dynes/cm2, and it was observed not only in HUVEC but also in HeLa cells, glioma cell lines, and skin fibroblasts. This in vitro study demonstrates that the response of MCP-1 gene to shear stress represents an immediate early gene activation and suggests that this gene is probably suppressed in EC that have been exposed to a constant shear stress. PMID- 8197119 TI - Granulocyte colony-stimulating factor receptor signaling involves the formation of a three-component complex with Lyn and Syk protein-tyrosine kinases. AB - Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that critically regulates the viability, proliferation, and differentiation of granulocytic precursors and the function of neutrophils by signaling through its receptor. Cloning of the human G-CSF receptor (G-CSFR) cDNA has demonstrated sequence homology with other members of the hematopoietic/cytokine receptor superfamily. G CSF stimulates the appearance of phosphotyrosine proteins in several types of human and murine myeloid cells. Since the receptor does not possess intrinsic tyrosine kinase activity, we hypothesized that G-CSFR interacts with and activates cytosolic protein-tyrosine kinases (PTKs). In vitro protein kinase assay of human G-CSFR immunoprecipitates demonstrated at least two tyrosine phosphoproteins, pp55 and pp70. We observed that G-CSF activated p53/p56lyn, a Src-related PTK, and p72syk, a non-Src-related PTK. Lyn and Syk were recovered in anti-G-CSFR immunoprecipitates; Lyn was detected in the absence of ligand. In addition, upon G-CSF stimulation, Lyn coimmunoprecipitated with Syk. Analysis of the G-CSFR amino acid sequence revealed a potential receptor activation motif for Syk. On the basis of immunoprecipitation and sequence analysis data, we propose that the human G-CSFR forms a three-component signaling complex with Lyn and Syk. Their sequential recruitment into the G-CSFR signaling complex demonstrates the coordinated involvement of two PTKs with a member of the hematopoietic/cytokine receptor superfamily. PMID- 8197120 TI - Synaptobrevin/vesicle-associated membrane protein (VAMP) of Aplysia californica: structure and proteolysis by tetanus toxin and botulinal neurotoxins type D and F. AB - Synaptobrevin/vesicle-associated membrane protein (VAMP) and syntaxin are potential vesicle donor and target membrane receptors of a docking complex that requires N-ethylmaleimide-sensitive factor (NSF) and soluble NSF-attachment proteins as soluble factors for vesicle fusion with target membranes. Members of this docking complex are the target of clostridial neurotoxins that act as zinc dependent proteases. Molecular cloning of the Aplysia californica synaptobrevin cDNA revealed a 180-residue polypeptide (M(r), 19,745) with a central transmembrane region and an atypically large C-terminal intravesicular domain. This polypeptide integrates into membranes at both the co- and posttranslational level, as shown by modification of an artificially introduced N-glycosylation site. The soluble and membrane-anchored forms of synaptobrevin are cleaved by the light chains of the botulinal toxins type D and F and by tetanus toxin involving the peptide bonds Lys49-Ile50, Gln48-Lys49, and Gln66-Phe67, respectively. The active center of teh tetanus toxin light chain was identified by site-specific mutagenesis. His233, His237, Glu234, and Glu270/271 are essential to this proteolytic activity. Modification of histidine residues resulted in loss of zinc binding, whereas a replacement of Glu234 only slightly reduced the zinc content. PMID- 8197121 TI - The nonpeptide WIN 64338 is a bradykinin B2 receptor antagonist. AB - We report the synthesis and in vitro biological activity of the nonpeptide bradykinin receptor antagonist WIN 64338, [[4-[[2 [[bis(cyclohexylamino)methylene]amino]-3-(2- naphthyl)-1 oxopropyl]amino]phenyl]methyl]tributylphosphonium chloride monohydrochloride. WIN 64338 inhibits [3H]-bradykinin binding to the bradykinin B2 receptor on human IMR 90 cells with a binding inhibition constant (Ki) of 64 +/- 8 nM and demonstrates competitive inhibition of bradykinin-stimulated 45Ca2+ efflux from IMR-90 cells (pA2 = 7.1). The antagonist inhibits bradykinin-mediated guinea pig ileum contractility (pA2 = 8.2) and has significantly weaker activity against acetylcholine-induced contractility in the same preparation. WIN 64338 is not active in a rabbit aorta bradykinin B1 receptor assay, demonstrating that it is a selective bradykinin B2 receptor antagonist. The compound inhibits [3H]quinuclidinyl benzilate binding to the rat brain muscarinic receptor (Ki = 350 nM) but is 25- to 100-fold more selective for the bradykinin receptor compared with other receptors against which it has been tested. Synthesis of WIN 64338 has provided a nonpeptide competitive bradykinin B2 antagonist active in both bradykinin radioligand binding and functional assays. PMID- 8197122 TI - Subunit dynamics in Escherichia coli preprotein translocase. AB - SecY, SecE, and band 1 copurify as the SecY/E integral membrane domain of Escherichia coli preprotein translocase. To measure the in vivo association of these polypeptides and assay possible exchange, plasmid-borne secY and secE genes were placed under control of the ara regulon and fused to DNA encoding the influenza hemagglutinin epitope. Cells were incubated with [35S]methionine, grown for a "chase" period, and then induced with arabinose to express epitope-tagged, nonradioactive SecY and SecE. Both the wild-type and epitope-tagged polypeptides assembled into functional, heterotrimeric SecY/E complex. However, immunoprecipitation with antibody to the epitope tag did not cross-precipitate radiolabeled SecY or SecE. Thus, these subunits normally associate stably in vivo. PMID- 8197123 TI - The combinatorial synthesis and chemical and biological evaluation of a 1,4 benzodiazepine library. AB - A library of 192 structurally diverse 1,4-benzodiazepine derivatives containing a variety of chemical functionalities including amides, carboxylic acids, amines, phenols, and indoles was constructed from three components, 2-aminobenzophenones, amino acids, and alkylating agents, by employing Geysen's pin apparatus [Geysen, H. M., Rodda, S. J., Mason, T. J., Tribbick, G. & Schoofs, P. G. (1987) J. Immunol. Methods 102, 259-274]. Rigorous analytical verification of the chemical integrity and yield of a representative collection of the diverse derivatives was carried out. In addition, the library of derivatives was evaluated for binding to the cholecystokinin A receptor by employing a competitive radio-ligand binding assay. This provided detailed structure versus activity relationships that were confirmed by independent large-scale synthesis and evaluation of several of the 1,4-benzodiazepine derivatives. PMID- 8197124 TI - Three-dimensional structure of cyanomet-sulfmyoglobin C. AB - The atomic structure of horse heart cyanomet-sulfmyoglobin C has been established by x-ray crystallographic techniques to a resolution of 2.0 A with an R value of 0.129. The protoheme IX prosthetic group of this thermodynamically stable sulfmyoglobin derivative has been converted to a chlorin in which the pyrrole ring bearing the 4-vinyl group is saturated and possesses an exocyclic thiolene ring. This study provides the three-dimensional structure of a protein with an iron-chlorin prosthetic group. The overall conformation of the surrounding polypeptide chain of the modified protein is very similar to that of the native protein. However, the addition of the sulfur atom has caused a distortion of the prosthetic group from that in the native protein to result in the repositioning of the side chains of some residues in the heme pocket. PMID- 8197125 TI - Chitin synthase 3 from yeast has zymogenic properties that depend on both the CAL1 and the CAL3 genes. AB - In previous studies, chitin synthase 3 (Chs3), the enzyme responsible for synthesis of most of the chitin present in the yeast cell, was found to be inactivated by incubation with trypsin, in contrast to other yeast chitin synthases (Chs1 and Chs2), which are stimulated by this treatment (chitin synthase; UDP-N-acetyl-D-glucosamine:chitin 4-beta-N-acetylglucosaminyl transferase, EC 2.4.1.16). It has now been found that the substrate UDPGlcNAc protects Chs3 against proteolytic inactivation. Treatment of Chs3-containing membranes with detergents drastically reduced the enzymatic activity. Activity could, however, be restored by subsequent incubation with trypsin or other proteases in the presence of UDPGlcNAc. Under such conditions, protease treatment stimulated activity as much as 10-fold. A change in divalent cation specificity after trypsin treatment suggests that the protease directly affects the enzyme molecule. Experiments with mutants in the three genes involved in Chs3 activity- CAL1, CAL2, and CAL3--showed that only CAL1 and CAL3 are required for the protease-elicited (zymogenic) activity. It is concluded that Chs3 is a zymogen and that the CAL2 product functions as its activator. The differences and possible similarities between Chs3 and the other chitin synthases are discussed. PMID- 8197126 TI - Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. AB - The met protooncogene product, Met, is the tyrosine kinase growth factor receptor for hepatocyte growth factor/scatter factor (HGF/SF). NIH 3T3 cells express HGF/SF endogenously and become tumorigenic in nude mice via an autocrine mechanism when murine Met is expressed ectopically (Metmu cells) or when human Met and human HGF/SF are coexpressed (HMH cells). Here, we show that Metmu and HMH cells are invasive in vitro and display enhanced protease activity necessary for the invasive phenotype. In experimental and spontaneous metastasis assays, Metmu or HMH cells metastasize to the lung, but lower numbers of subcutaneously injected Metmu and HMH cells produced invasive tumors in the heart, diaphragm, salivary gland, and retroperitoneum. It has been reported elsewhere that Met expression increased with tumor passage in athymic nude mice, and these tumor explants show enhanced activity in the metastasis assays. Autocrine-mediated Met HGF/SF signal transduction in NIH 3T3 mesenchymal cells may provide an important system for understanding the biological process of metastasis. PMID- 8197127 TI - Simulated responses of cerebellar Purkinje cells are independent of the dendritic location of granule cell synaptic inputs. AB - Cerebellar Purkinje cell responses to granule cell synaptic inputs were examined with a computer model including active dendritic conductances. Dendritic P-type Ca2+ channels amplified postsynaptic responses when the model was firing at a physiological rate. Small synchronous excitatory inputs applied distally on the large dendritic tree resulted in somatic responses of similar size to those generated by more proximal inputs. In contrast, in a passive model the somatic postsynaptic potentials to distal inputs were 76% smaller. The model predicts that the somatic firing response of Purkinje cells is relatively insensitive to the exact dendritic location of synaptic inputs. We describe a mechanism of Ca2+ mediated synaptic amplification, based on the subspiking threshold recruitment of P-type Ca2+ channels in the dendritic branches surrounding the input site. PMID- 8197128 TI - Molecular cloning, tissue distribution, and expression of a 14-kDa bile acid binding protein from rat ileal cytosol. AB - A cDNA clone encoding the major intestinal cytosolic 14-kDa bile acid-binding protein (14-kDa I-BABP) was isolated from a rat ileal lambda gt22A library following immunoscreening using a monospecific antiserum raised against a 14-kDa polypeptide found in the rat ileal cytosol. One clone of 516 bp encoded a 128 amino acid protein with a predicted molecular mass of 14,544 Da. The deduced amino acid sequence of 14-kDa I-BABP showed 100% homology to rat intestinal 15 kDa protein (I-15P) and 72% homology to porcine 15-kDa gastrotropin, whereas comparison of I-BABP to rat 14-kDa fatty acid-binding proteins of liver, intestine, and heart revealed homologies of 44%, 25%, and 28%, respectively. Northern blot analysis revealed a single transcript of approximately 0.5 kb in ileum and ovary; however, the abundance of I-BABP mRNA was much greater in ileum than in ovary. No transcript was seen in RNA extracted from stomach, jejunum, colon, liver, adrenal, brain, heart, kidney, or testis. Transfection of the I BABP cDNA into COS-7 cells resulted in the expression of a 14-kDa protein that was identical to the ileal cytosolic I-BABP as determined by immunoblotting. Photoaffinity labeling of expressed 14-kDa protein was saturable with respect to increasing concentrations of 7,7-azo[3H]taurocholate (Km, 83.3 microM; Vmax, 6.7 pmol/mg per 5 min). Taurocholate inhibited 7,7-azotaurocholate labeling by > 96% with lesser inhibition by taurochenodeoxycholate (83.1%), chenodeoxycholate (74.6%), cholate (50.5%), and progesterone (38.5%), whereas oleic acid and estradiol did not inhibit binding. PMID- 8197129 TI - Mobile Minos elements from Drosophila hydei encode a two-exon transposase with similarity to the paired DNA-binding domain. AB - Elements related to the Tc1-like Minos mobile element have been cloned from Drosophila hydei and sequenced. Southern blot and sequence analyses show that (i) the elements are actively transposing in the Drosophila hydei germ line, (ii) they are characterized by a striking degree of sequence and size homogeneity, and (iii) like Tc1, they insert at a TA dinucleotide that is probably duplicated during the process. The nucleotide sequences of two elements, Minos-2 and Minos 3, differ at only one position from each other and contain two nonoverlapping open reading frames that are separated by a putative 60-nucleotide intron. The amino-terminal part of the Minos putative transposase shows sequence similarity to the paired DNA-binding domain. Forced transcription of a modified Minos element that was introduced into the Drosophila melanogaster germ line by P element-mediated transformation resulted in the production of accurately spliced polyadenylylated RNA molecules. It is proposed that Minos-2 and/or Minos-3 may encode an active transposase containing an amino-terminal DNA-binding domain that is distantly related to the paired DNA-binding domain. PMID- 8197130 TI - Beta 2-microglobulin gene mutations: a study of established colorectal cell lines and fresh tumors. AB - The technique of single-strand conformation polymorphism (SSCP) was used to screen a series of 37 established colorectal cell lines, 22 fresh tumor samples, and 22 normal DNA samples for mutations in the beta 2-microglobulin gene. Exon 1 (including the leader peptide sequence) and exon 2 were screened separately. Six of 37 colorectal cell lines and 1 of 22 fresh tumors were shown to contain mutations, whereas no mutations were detected in the normal DNA samples. Sequencing of these mutations showed that an 8-bp CT repeat in the leader peptide sequence was particularly variable, since 3 of the cell lines and one fresh tumor sample have deletions in this region. In the related cell lines, DLD-1 and HCT 15, two similar mutations were identified, a C-->A substitution in codon 10 and a G-->T mutation in the splice sequence of intron 1. Expression of beta 2 microglobulin was examined using a series of monoclonal antibodies in an ELISA system. Reduced expression correlated with a mutation in one allele of beta 2 microglobulin, whereas loss of expression was seen in instances where a line was homozygous for a mutation or heterozygous for two mutations. PMID- 8197131 TI - Molecular basis of dark-eyed albinism in the mouse. AB - Dark-eyed albino (C44H) is a recessive allele at the mouse albino (c) locus, which encodes tyrosinase (monophenol,L-dopa:oxygen oxidoreductase, EC 1.14.18.1), the key enzyme in melanin synthesis. Similar to type IB oculocutaneous albinism in humans, overall production of pigment is greatly reduced in dark-eyed albino mice and obvious only in the eyes. We have studied the molecular basis of the c44H mutation and show that expression of the tyrosinase gene is not affected. After sequencing tyrosinase cDNA isolated from c44H/c44H homozygotes, we uncovered a single base alteration from wild type leading to a serine-to isoleucine exchange. The importance of this mutation was demonstrated by generating transgenic mice containing a mutated tyrosinase minigene. This showed that the single base change was sufficient to severely depress pigment production in transgenic mice. We therefore conclude that the point mutation is responsible and sufficient to generate the dark-eyed albino phenotype. PMID- 8197132 TI - Specificity of protein kinase inhibitor peptides and induction of long-term potentiation. AB - Previous studies have used synthetic peptide analogs, corresponding to sequences within the pseudosubstrate domain of protein kinase C (PKC) or the autoregulatory domain of Ca2+/calmodulin-dependent protein kinase II (CaMKII), in attempts to define the contribution of each of these protein kinases to induction of long term potentiation (LTP). However, the specificity of these inhibitor peptides is not absolute. Using intracellular delivery to rat CA1 hippocampal neurons, we have determined the relative potency of two protein kinase inhibitor peptides, PKC-(19-36) and [Ala286]CaMKII-(281-302), as inhibitors of the induction of LTP. Both peptides blocked the induction of LTP; however, PKC-(19-36) was 30-fold more potent than [Ala286]CaMKII-(281-302). The relative specificity of PKC-(19-36), [Ala286]CaMKII-(281-302), and several other CaMKII peptide analogs for protein kinase inhibition in vitro was also determined. A comparison of the potencies of PKC-(19-36) and [Ala286]CaMKII-(281-302) in the physiological assay with their Ki values for protein kinase inhibition in vitro indicates that the blockade of induction of LTP observed for each peptide is attributable to inhibition of PKC. PMID- 8197133 TI - Advanced glycation end products contribute to amyloidosis in Alzheimer disease. AB - Alzheimer disease (AD) is characterized by deposits of an aggregated 42-amino acid beta-amyloid peptide (beta AP) in the brain and cerebrovasculature. After a concentration-dependent lag period during in vitro incubations, soluble preparations of synthetic beta AP slowly form fibrillar aggregates that resemble natural amyloid and are measurable by sedimentation and thioflavin T-based fluorescence. Aggregation of soluble beta AP in these in vitro assays is enhanced by addition of small amounts of pre-aggregated beta-amyloid "seed" material. We also have prepared these seeds by using a naturally occurring reaction between glucose and protein amino groups resulting in the formation of advanced "glycosylation" end products (AGEs) which chemically crosslink proteins. AGE modified beta AP-nucleation seeds further accelerated aggregation of soluble beta AP compared to non-modified "seed" material. Over time, nonenzymatic advanced glycation also results in the gradual accumulation of a set of posttranslational covalent adducts on long-lived proteins in vivo. In a standardized competitive ELISA, plaque fractions of AD brains were found to contain about 3-fold more AGE adducts per mg of protein than preparations from healthy, age-matched controls. These results suggest that the in vivo half-life of beta-amyloid is prolonged in AD, resulting in greater accumulation of AGE modifications which in turn may act to promote accumulation of additional amyloid. PMID- 8197134 TI - Transcription factor ISGF-3 formation requires phosphorylated Stat91 protein, but Stat113 protein is phosphorylated independently of Stat91 protein. AB - Transcription factor ISGF-3 is a multiprotein, interferon alpha-activated transcription complex consisting of a 48-kDa DNA-binding protein and two proteins termed Stats (for signal transducers and activators of transcription) that become phosphorylated on tyrosine in the cell cytoplasm, a 113-kDa and either a 91- or 84-kDa polypeptide, the latter two of which arise from differentially spliced mRNAs. Using cell lines lacking the Stat91 or Stat84 proteins, we show that mutations in several different sites in the 91-kDa protein block the interferon alpha-induced phosphorylation of the 91-kDa protein and subsequent ISGF-3 formation. Although correct tyrosine phosphorylation on residue 690 of the Stat113 protein occurs independent of the Stat91/84 protein, the Stat113 phosphoprotein by itself moves to the cell nucleus much less efficiently in the absence of phosphorylated Stat91/84 protein. PMID- 8197135 TI - Mitogen-stimulated phosphorylation of histone H3 is targeted to a small hyperacetylation-sensitive fraction. AB - Diverse agents, including growth factors and phorbol esters, induce rapid transcriptional activation of a subset of immediate-early (IE) genes that include the protooncogenes c-fos and c-jun. Among the earliest nuclear signaling events concomitant with IE gene activation is the phosphorylation of nucleosomal histone H3 in its basically charged N-terminal tail. This highly conserved domain is also subject to reversible posttranslational acetylation at specific lysine residues, a process implicated in transcriptional regulation. We show here that H3 phosphorylation associated with G0-G1 transition affects only a small fraction of this histone in the nucleus. Moreover, this fraction is biochemically distinct from bulk H3 in being extremely sensitive to sodium butyrate-induced hyperacetylation. However, acetylation itself does not predispose H3 to phosphorylation, nor does phosphorylation predispose H3 to enhanced acetylation. Further, selectivity is not based on preferential modification of particular histone H3 subtypes. Thus, the mitogen-regulated kinase that phosphorylates histone H3 is restricted to a small subset of nucleosomes that is especially susceptible to hyperacetylation. PMID- 8197136 TI - Dynamic synaptic modification threshold: computational model of experience dependent plasticity in adult rat barrel cortex. AB - Previous electrophysiological experiments have documented the response of neurons in the adult rat somatic sensory ("barrel") cortex to whisker movement after normal experience and after periods of experience with all but two whiskers trimmed close to the face (whisker "pairing"). To better understand how the barrel cortex adapts to changes in the flow of sensory activity, we have developed a computational model of a single representative barrel cell based on the Bienenstock, Cooper, and Munro (BCM) theory of synaptic plasticity. The hallmark of the BCM theory is the dynamic synaptic modification threshold, theta M, which dictates whether a neuron's activity at any given instant will lead to strengthening or weakening of the synapses impinging on it. The threshold theta M is proportional to the neuron's activity averaged over some recent past. Whisker pairing was simulated by setting input activities of the cell to the noise level, except for two inputs that represented untrimmed whiskers. Initially low levels of cell activity, resulting from whisker trimming, led to low values for theta M. As certain synaptic weights potentiated, due to the activity of the paired inputs, the values of theta M increased and after some time their mean reached an asymptotic value. This saturation of theta M led to the depression of some inputs that were originally potentiated. The changes in cell response generated by the model replicated those observed in in vivo experiments. Previously, the BCM theory has explained salient features of developmental experience-dependent plasticity in kitten visual cortex. Our results suggest that the idea of a dynamic synaptic modification threshold, theta M, is general enough to explain plasticity in different species, in different sensory systems, and at different stages of brain maturity. PMID- 8197137 TI - Cell size predicts morphological complexity in the brains of frogs and salamanders. AB - The morphological organization of the brain of frogs and salamanders varies greatly in the degree to which it is subdivided and differentiated. Members of these taxa are visually oriented predators, but the morphological complexity of the visual centers in the brain varies interspecifically. We give evidence that the morphological complexity of the amphibian tectum mesencephali, the main visual center, can be predicted from knowledge of cell size, which varies greatly among these taxa. Further, cell size is highly correlated with genome size. Frogs with small cells have more complex morphologies of the tectum than do those with large cells independent of body and brain size. In contrast, in salamanders brain body size relationships also are correlated with morphological complexity of the brain. Small salamanders with large cells have the simplest tecta, whereas large salamanders with small cells exhibit the most complex tectal morphologies. Increases in genome, and consequently cell size, are associated with a decrease in the differentiation rate of nervous tissue, which leads to the observed differences in brain morphology. On the basis of these findings we hypothesize that important features of the structure of the brain can arise independently of functional demands, from changes at a lower level of organismal organization--in this case increase in genome size, which induces simplification of brain morphology. PMID- 8197138 TI - High-resolution laser desorption mass spectrometry of peptides and small proteins. AB - Matrix-assisted laser desorption/ionization (MALDI) has been used with an external ion source Fourier-transform mass spectrometer to obtain the highest mass resolution ever, to our knowledge, demonstrated for laser-produced ions (m/delta m = 1,100,000 for [Arg8]vasopressin, 228,000 for melittin, and 90,000 for bovine insulin). The peaks in the isotope cluster for bovine insulin are fully resolved, and the mass measurement accuracy is an order of magnitude better than can be achieved with time-of-flight mass spectrometry. With the method described here, analyte is applied to a sample probe and mixed with a solution containing a matrix material (2,5-dihydroxybenzoic acid) that strongly absorbs ultraviolet light. Upon irradiation with a pulse from an excimer laser (353 nm, 2 mJ), a large number of intact protonated molecular ions are produced. The ions are focused by a 117-cm-long quadrupole ion guide and injected into an ion cyclotron resonance analyzer cell located inside the bore of a 6.5-T superconducting magnet. A pulse of argon buffer gas cools the ions prior to detection. One of the principal advantages of an external ion source Fourier transform mass spectrometer is that the ion formation and ion detection processes are separated and can be independently optimized. PMID- 8197139 TI - Rat liver endocytic coated vesicles do not exhibit ATP-dependent acidification in vitro. AB - Coated vesicle fractions from a variety of tissues have been found to contain a vacuolar proton ATPase. Since these fractions contain both plasma membrane- and Golgi-derived coated vesicles, we sought to determine specifically whether endocytic coated vesicles from rat liver contain an active vacuolar proton ATPase. Endocytic vesicles (coated vesicles and endosomes) were selectively labeled with pH-sensitive endocytic tracers (fluorescein isothiocyanate-dextran or -asialoorsomucoid). Coated vesicles were then separated from endosomes by sucrose density gradient centrifugation. Although the endosomal fractions were found to exhibit significant ATP-dependent acidification activity, highly purified coated vesicles containing pH-sensitive endocytic tracers were unable to generate a pH gradient in response to ATP addition. The coated vesicles could be passively acidified, however, by creating potassium diffusion potentials, indicating that they were in fact capable of maintaining proton gradients. Moreover, significant ATP-dependent acidification activity was observed when the coated vesicle fractions were assayed using the nonselective externally added pH probe acridine orange. Thus, it appears that rat liver endocytic coated vesicles do not contain a functional proton pump. The active vacuolar proton ATPase found in these fractions instead reflected the presence of Golgi-derived coated vesicles or contaminating membranes. PMID- 8197140 TI - A G protein-coupled receptor with low density lipoprotein-binding motifs suggests a role for lipoproteins in G-linked signal transduction. AB - We have isolated and analyzed a cDNA from the central nervous system of the mollusc Lymnaea stagnalis encoding a putative receptor, which might be a natural hybrid between two different classes of receptor proteins. Preceded by a signal peptide, two types of repeated sequences are present in the N-terminal part of the protein. The first repeat displays a high sequence similarity to the extracellular binding domains of the low density lipoprotein receptor, which binds and internalizes cholesterol-containing apolipoproteins. The second repeat and the C-terminal part of the Lymnaea receptor are very similar to regions of a specific class of guanine nucleotide-binding protein-coupled receptors, the mammalian glycoprotein hormone receptors. The mRNA encoding the receptor is predominantly expressed in a small number of neurons within the central nervous system and to a lesser extent in the heart. PMID- 8197141 TI - The red queen reigns in the kingdom of RNA viruses. AB - Two clonal populations of vesicular stomatitis virus of approximately equal relative fitness were mixed together and allowed to compete during many transfers in vitro as large virus populations. Eventually, one or the other population suddenly excluded its competitor population, yet both the winners and losers exhibited absolute gains in fitness. Our results agree with the predictions of two major theories of classical population biology; the Competitive Exclusion Principle and the Red Queen's Hypothesis, where (in Lewis Carroll's words) "it takes all the running you can do to keep in the same place." PMID- 8197142 TI - Gamma interferon activates a previously undescribed Ca2+ influx in T lymphocytes from patients with multiple sclerosis. AB - Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. The etiology of the disease is still unknown. Activated T lymphocytes are considered essential in mediating the inflammatory process leading to demyelination in MS. They operate through a complex network of cytokines among which gamma interferon (gamma-IFN) plays a key role. Here we report that exposure to gamma-IFN of T lymphocytes from patients with MS activates, by a protein kinase C-mediated pathway, a previously undescribed gamma IFN-activated Ca2+ influx, functionally coupled to the gamma-IFN receptor. The influx mainly expressed by CD4+ T lymphocytes, was found in 12 of 15 (80%) patients with clinically active MS and in 14 of 30 (46%) patients with stable MS. The influx was found in only 3 of 24 (12%) control patients and in none of the 15 healthy subjects studied. Our results document the appearance in MS lymphocytes of a gamma-IFN-activated, protein kinase C-dependent, Ca2+ influx that might be due to the expression of a new cation-specific plasmalemma channel. This finding suggests that at least part of gamma-IFN's contribution to the pathogenesis of MS is exerted through a Ca(2+)-dependent regulation of T lymphocyte activity. PMID- 8197143 TI - Inversion of the Bohr effect upon oxygen binding to 24-meric tarantula hemocyanin. AB - The Bohr effect describes the usually negative coupling between the binding of oxygen and the binding of protons to respiratory proteins. It was first described for hemoglobin and provides for an optimal oxygen supply of the organism under changing physiological conditions. Our measurements of both oxygen and proton binding to the 24-meric tarantula hemocyanin establish the unusual case where a respiratory protein binds protons at low degrees of oxygenation but releases protons at high degrees of oxygenation. In contrast to what is observed with hemoglobin and other respiratory proteins, this phenomenon amounts to the inversion of the Bohr effect in the course of an oxygen-binding curve at a given pH value. Therefore, protons in spider blood can act either as allosteric activators or as allosteric inhibitors of oxygen binding, depending on the degree of oxygenation of hemocyanin. These functional properties of tarantula hemocyanin, which cannot be explained by classical allosteric models, require at least four different conformational states of the subunits. Inspection of the known x-ray structures of closely related hemocyanins suggests that salt bridges between completely conserved histidine and glutamate residues located at particular intersubunit interfaces are responsible for the observed phenomena. PMID- 8197144 TI - Double-stranded DNA templates can induce alpha-helical conformation in peptides containing lysine and alanine: functional implications for leucine zipper and helix-loop-helix transcription factors. AB - Transcription factors of the basic-leucine zipper and basic-helix-loop-helix families specifically recognize DNA by means of intrinsically flexible peptide domains that assume an alpha-helical conformation upon binding to target DNA sequences. We have investigated the nonspecific interactions that underlie specific DNA recognition. Circular dichroism measurements showed that 20-bp double-stranded DNA oligonucleotides can act as templates to promote random coil- >alpha-helix transitions in short peptides containing alanine and lysine. This conformational change takes place without altering the structure of the DNA, and neither specific peptide-DNA contacts nor cooperative interactions between peptides are necessary. The conformational change does require (i) double stranded (but not single-stranded) oligodeoxynucleotides in either the B or the B' conformation and (ii) peptides that can form positively charged amphipathic alpha-helices. In 10 mM Na2HPO4 (pH 7.5; 10 degrees C), the excess free-energy contribution of the DNA template to the stability of the alpha-helical form of the oligopeptides tested was delta Gex = -0.15 (+/- 0.07) kcal/mol per lysine residue. The implications of these results for the thermodynamics and kinetics of DNA target site selection by basic-leucine zipper and basic-helix-loop-helix regulatory proteins are discussed. PMID- 8197145 TI - cGMP binding sites on photoreceptor phosphodiesterase: role in feedback regulation of visual transduction. AB - A central step in vertebrate visual transduction is the rapid drop in cGMP levels that causes cGMP-gated ion channels in the photoreceptor cell membrane to close. It has long been a puzzle that the cGMP phosphodiesterase (PDE) whose activation causes this decrease contains not only catalytic sites for cGMP hydrolysis but also noncatalytic cGMP binding sites. Recent work has shown that occupancy of these noncatalytic sites slows the rate of PDE inactivation. We report here that PDE activation induced by activated transduction lowers the cGMP binding affinity for noncatalytic sites on PDE and accelerates the dissociation of cGMP from these sites. These sites can exist in three states: high affinity (Kd = 60 nM) for the nonactivated PDE, intermediate affinity (Kd approximately 180 nM) when the enzyme is activated in a complex with transducin, and low affinity (Kd > 1 microM) when transducin physically removes the inhibitory subunits of PDE from the PDE catalytic subunits. Activation of PDE by transducin causes a 10-fold increase in the rate of cGMP dissociation from one of the two noncatalytic sites; physical removal of the inhibitory subunits from the PDE catalytic subunits further accelerates the cGMP dissociation rate from both sites > 50-fold. Because PDE molecules lacking bound cGMP inactivate more rapidly, this suggests that a prolonged cGMP decrease may act as a negative feedback regulator to generate the faster, smaller photoresponses characteristic of light-adapted photoreceptors. PMID- 8197146 TI - X-ray structure determination at 2.6-A resolution of a lipoate-containing protein: the H-protein of the glycine decarboxylase complex from pea leaves. AB - H-protein, a lipoic acid-containing protein of the glycine decarboxylase (EC 1.4.4.2) complex from pea (Pisum sativum) was crystallized from ammonium sulfate solution at pH 5.2 in space group P3(1)21. The x-ray crystal structure was determined to 2.6-A resolution by multiple isomorphous replacement techniques. The structure was refined to an R value of 23% for reflections between 15- and 2.6-A resolution (F > 2 sigma), including the lipoate moiety and 50 water molecules, for the two protein molecules of the asymmetric unit. The 131-amino acid residues form seven beta-strands arranged into two antiparallel beta-sheets forming a "sandwich" structure. One alpha-helix is observed at the C-terminal end. The lipoate cofactor attached to Lys-63 is located in the loop of a hairpin configuration. The lipoate moiety points toward the residues His-34 and Asp-128 and is situated at the surface of the H-protein. This allows the flexibility of the lipoate arm. This is the first x-ray determination of a lipoic acid containing protein, and the present results are in agreement with previous theoretical predictions and NMR studies of the catalytic domains of lipoic acid- and biotin-containing proteins. PMID- 8197147 TI - Tumor necrosis factor alpha inhibits signaling from the insulin receptor. AB - Insulin resistance is a common problem associated with infections and cancer and, most importantly, is the central component of non-insulin-dependent diabetes mellitus. We have recently shown that tumor necrosis factor (TNF) alpha is a key mediator of insulin resistance in animal models of non-insulin-dependent diabetes mellitus. Here, we investigate how TNF-alpha interferes with insulin action. Chronic exposure of adipocytes to low concentrations of TNF-alpha strongly inhibits insulin-stimulated glucose uptake. Concurrently, TNF-alpha treatment causes a moderate decrease in the insulin-stimulated autophosphorylation of the insulin receptor (IR) and a dramatic decrease in the phosphorylation of IR substrate 1, the major substrate of the IR in vivo. The IR isolated from TNF alpha-treated cells is also defective in the ability to autophosphorylate and phosphorylate IR substrate 1 in vitro. These results show that TNF-alpha directly interferes with the signaling of insulin through its receptor and consequently blocks biological actions of insulin. PMID- 8197148 TI - Posttranscriptional mRNA processing as a mechanism for regulation of human A1 adenosine receptor expression. AB - The human A1 adenosine receptor gene contains six exons with exons 1, 2, 3, 4, and part of 5 representing 5' untranslated regions. Reverse transcription-PCR with exon-specific primers showed two distinct transcripts containing either exons 3, 5, and 6 or exons 4, 5, and 6, with exons 3 and 4 being mutually exclusive. No mature mRNAs containing exons 1 and 2 have been detected. All human tissues that express any A1 receptors contain mRNA with exons 4, 5, and 6. Tissues which express high levels of A1 receptors contain mRNA with exons 3, 5, and 6. Exon 4 contains two upstream ATG codons whereas exon 3 contains none. COS cells transfected with expression vectors containing exon 4 (exons 1-6, 3-6, or Ex4-6) express much lower levels of A1 receptors than vectors without exon 4 (exons 3, 5, and 6). Mutation of upstream ATG codons in exon 4 leads to 3- to 7 fold increased A1 receptor expression, up to the level seen with the construct containing exons 3, 5, and 6. Thus, in human tissues "basal" levels of A1 receptors can be expressed by use of mRNA containing exons 4, 5, and 6, but when high levels are needed, alternative transcripts with exons 3, 5, and 6 are produced. PMID- 8197149 TI - Allele-specific parental imprinting of dzr1, a posttranscriptional regulator of zein accumulation. AB - Parental imprinting describes the phenomenon of unequivalent gene function based on transmission from the female or male parent. We have discovered parental imprinting of an allele of the dzr1 locus that posttranscriptionally regulates the accumulation of 10-kDa zein in the maize endosperm. The imprinted allele of MO17 inbred origin, dzr1 + MO17, conditions low accumulation of the 10-kDa zein and is dominant when transmitted through the female but recessive when transmitted through the male. Analyzing endosperms with equal parental contributions of dzr1 + MO17 ruled out the possibility that the unequivalent phenotype of dzr1 + MO17 was due to parental dosage imbalance in the triploid endosperm. Second-generation studies show that the dominant or recessive phenotype of dzr1 + MO17 is determined at every generation based on immediate parental origin with no grandparental effect. PMID- 8197150 TI - Spatial games and the maintenance of cooperation. AB - The Prisoner's Dilemma (PD) is a widely employed metaphor for problems associated with the evolution of cooperative behavior. We have recently proposed an alternative approach to the PD, by exploring "spatial games" in which players- who are either pure cooperators, C, or pure defectors, D--interact with neighbors in some spatial array; in each generation, players add up the scores from all encounters, and in the next generation a given cell is retained by its previous owner or taken over by a neighbor, depending on who has the largest score. Over a wide range of the relevant parameters, we find that C and D persist together indefinitely (without any of the complex strategies that remember past encounters, and anticipate future ones, which characterize essentially all previous work on the iterated PD). Our earlier work, however, dealt with symmetric spatial lattices in two dimensions, deterministic winning and discrete time. We show here that the essential results remain valid in more realistic situations where the spatial distributions of cells are random in two or three dimensions, and where winning is partly probabilistic (rather than being determined by the largest local total). The essential results also remain valid (pace Huberman and Glance [Huberman, B. A. & Glance, N. S. (1993) Proc. Natl. Acad. Sci. USA 90, 7716-7718]) when interactions occur in continuous rather than discrete time. PMID- 8197151 TI - Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solution and applications. AB - We present an analytic solution for the scattering of diffuse photon density waves by spherical inhomogeneities within turbid media. The analytic result is compared to experimental measurements. Close agreement between theory and experiment permits the use of the theory to determine the properties of unknown sphere-like objects embedded in turbid media. The analytic solution is extended to encompass several problems of practical interest in imaging, including the influence of multiple sources, multiple objects, and boundaries on the characterization of spherical inhomogeneities. We also extend the solution to encompass time-domain measurements. PMID- 8197152 TI - Biochemical and pharmacological profile of a potent and selective endothelin B receptor antagonist, BQ-788. AB - We describe the characteristics of a potent and selective endothelin (ET) B receptor antagonist, BQ-788 [N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma methylleucyl-D -1- methoxycarbonyltryptophanyl-D-norleucine]. In vitro, this compound potently and competitively inhibits 125I-labeled endothelin 1 (ET-1) binding to ETB receptors on human Girardi heart cells (IC50, 1.2 nM) but only poorly inhibits the binding to ETA receptors on human neuroblastoma cell line SK N-MC cells (IC50, 1300 nM). In isolated rabbit pulmonary arteries, BQ-788 shows no agonist activity up to 10 microM and competitively antagonizes the vasoconstriction induced by an ETB-selective agonist, BQ-3020 (pA2, 8.4). In rat, an ETA-selective antagonist, BQ-123 (1 mg/kg, i.v.), does not affect transient depressor response to ET-1 (0.3 nmol/kg, i.v.) but potently inhibits following sustained pressor response; vice versa, BQ-788 (1 mg/kg, i.v.) abolishes the depressor response, resulting in a rapid onset of apparently enhanced pressor response. Thus, being a potent and selective ETB receptor antagonist, BQ-788 may be considered as a powerful tool for investigating the role of ET in physiological and pathological processes. PMID- 8197153 TI - Membrane-derived second messenger regulates x-ray-mediated tumor necrosis factor alpha gene induction. AB - Cells adapt to adverse environmental conditions through a wide range of responses that are conserved throughout evolution. Physical agents such as ionizing radiation are known to initiate a stress response that is triggered by the recognition of DNA damage. We have identified a signaling pathway involving the activation of phospholipase A2 and protein kinase C in human cells that confers x ray induction of the tumor necrosis factor alpha gene. Treatment of human cells with ionizing radiation or H2O2 was associated with the production of arachidonic acid. Inhibition of phospholipase A2 abolished radiation-mediated arachidonate production as well as the subsequent activation of protein kinase C and tumor necrosis factor alpha gene expression. These findings demonstrate that ionizing radiation-mediated gene expression in human cells is regulated in part by extranuclear signal transduction. One practical application of phospholipase A2 inhibitors is to ameliorate the adverse effects of radiotherapy associated with tumor necrosis factor alpha production. PMID- 8197154 TI - Stable intrachain and interchain complexes of neurofilament peptides: a putative link between Al3+ and Alzheimer disease. AB - The etiologic role of Al3+ in Alzheimer disease has been controversial. Circular dichroism (CD) spectroscopic studies on two synthetic fragments of human neurofilament protein mid-sized subunit (NF-M), NF-M13 (KSPVPKSPVEEKG) and NF-M17 (EEKGKSPVPKSPVEEKG), and their alanine-substituted and/or serine-phosphorylated derivatives were carried out in an attempt to find a molecular mechanism for the effect of Al3+ to induce aggregation of neuronal proteins or their catabolic fragments. Al3+ and Ca2+ ions were found to induce beta-pleated sheet formation in the phosphorylated fragments. The cation sensitivity depended on the length and charge distribution of the sequence and site of phosphorylation. Al3+-induced conformational changes were irreversible to citric acid chelation, whereas Ca(2+) induced conformational changes were reversible with citric acid. Studies of the alanine derivatives demonstrated which residues affected Al3+ or Ca2+ binding. Peptides containing at least one free (nonphosphorylated) serine residue were shown to form an intramolecular Al3+ complex, rather than an intermolecular one. In the intramolecular (intrachain) complex, the ligand function of the deprotonated serine hydroxyl was delineated [(Al.pepH-1)-type complex]. Ca2+ ions did not show a tendency for intramolecular complexing. The potential role of Al3+ in Alzheimer disease tangle and plaque formation is strongly suggested. PMID- 8197155 TI - Amino acid receptors of midget and parasol ganglion cells in primate retina. AB - Primate retinas contain two major ganglion cell types. Midget (or P type) cells have relatively sustained responses to light; the amplitude and polarity of these responses vary with stimulus wavelength. Parasol (or M type) cells are more sensitive to stimulus contrast and respond more transiently but are not selective for color. Both types can be further subdivided into a and b subtypes, according to the level of their dendritic stratification in the inner plexiform layer. To determine whether differences in receptors for amino acid transmitters are the basis for any differences in ganglion cell light responses, we made whole-cell, patch-clamp recordings from identified ganglion cells in slice preparations of macaque and baboon retinas. We found that midget and parasol cells of both a and b types had similar responses to excitatory amino acids, including kainate, alpha amino-3-hydroxy-5-methylisoxalzole-4-propionic acid, and N-methyl-D-aspartate, with reversal potentials near the equilibrium potential for cations. Kainate responses were blocked by 6,7-dinitroquinoxaline, and N-methyl-D-aspartate responses were blocked by D-(-)-2-amino-7-phosphonoheptanoic acid. The four types of ganglion cells also had similar responses to bath-applied inhibitory amino acids. All cells had both gamma-aminobutyric acid and glycine receptors with reversal potentials near the equilibrium potential for Cl-, and the relative amplitudes of the responses to excitatory and inhibitory amino acids were similar among the various cell types. These results suggest that the differences in response properties of the different classes of ganglion cells in primate retina may be determined, to a significant degree, by the properties of the amacrine and bipolar cells that provide their input rather than by the nature of their postsynaptic receptors. PMID- 8197156 TI - The calcitonin gene is expressed in salmon gills. AB - Calcitonin is an important physiological regulator of salmon gills. Although the calcitonin receptor was found in salmon gills, the critical question concerning the source of the hormone remained unanswered. In this communication, evidence is presented for expression of calcitonin mRNA and its encoded peptide in gills of the pink salmon, Oncorhynchus gorbuscha. The expression of calcitonin gene transcripts was demonstrated by reverse transcription-polymerase chain reaction, Southern hybridization, and sequencing. The sequencing identified a sequence corresponding to that of exon 4 of the salmon calcitonin gene. Expression of the encoded calcitonin gene in gills was detected by radioimmunoassay in gill extracts. This synthesis of calcitonin in gills, which also possess specific receptors to the peptide, suggests function of an autocrine or paracrine process producing calcitonin in this tissue. These observations confirm and extend previous reports on the physiological role of calcitonin in fish gills. PMID- 8197157 TI - LR1 regulates c-myc transcription in B-cell lymphomas. AB - LR1 is a 106-kDa sequence-specific DNA-binding protein first identified as a potential regulator of immunoglobulin class switch recombination in B lymphocytes. Here we report that LR1 binds to a site 310 nt upstream of the human c-myc P1 promoter. Mutation of this site decreases reporter gene expression 5.5 fold in the Burkitt lymphoma line Raji and 3.8-fold in the lymphoma line BJAB. These experiments show that LR1 can function as a transcription factor and identify it as a cell type-specific activator of c-myc expression. There are multiple matches to the LR1 recognition consensus at the immunoglobulin heavy chain locus and at c-myc, which further suggests that LR1 may play a dual role, facilitating c-myc translocation as well as regulating c-myc transcription. PMID- 8197158 TI - Direct determination of layer packing for a phospholipid solid solution at 0.32 nm resolution. AB - Electron diffraction intensity data were collected from a 2:3 binary solid solution of two homologous phosphatidylethanolamines (1,2-dimyristoyl-sn glycerophosphoethanolamine and 1,2-dipalmitoyl-sn-glycerophosphoethanolamine) epitaxially oriented by cocrystallization with naphthalene. The layer packing was determined directly by predicting the value of 12 of the 17 phases from sigma 1- and sigma 2-triplet invariants in space group P1. A reverse Fourier transform of the resulting potential maps provides estimates for three other phases and the two remaining ones were found by generating maps for the 2(2) = 4 possible phase combinations and then testing the smoothness of the potential profile of the hydrocarbon chain packing. The same phase solution can be found by translating a molecular model (based on the known x-ray crystal structure of a shorter homologue) past the unit cell origin. The solid solution is found to retain a stable polar group packing while the statistical occupancy of two terminal-chain carbons is expressed by a reduced potential profile at the nonpolar interface at the bilayer center. PMID- 8197159 TI - Mammalian mitogen-activated protein kinase kinase kinase (MEKK) can function in a yeast mitogen-activated protein kinase pathway downstream of protein kinase C. AB - Mitogen-activated protein kinase cascades are conserved in fungal, plant, and metazoan species. We expressed murine MAP kinase kinase kinase (MEKK) in the yeast Saccharomyces cerevisiae to determine whether this kinase functions as a general or specific activator of genetically and physiologically distinct MAP kinase-dependent signaling pathways and to investigate how MEKK is regulated. Expression of MEKK failed to correct the mating deficiency of a ste11 delta mutant that lacks an MEKK homolog required for mating. MEKK expression also failed to induce expression of a reporter gene controlled by the HOG1 gene product (Hog1p), a yeast MAP kinase homolog involved in response to osmotic stress. Expression of MEKK did correct the cell lysis defect of a bck1 delta mutant that lacks an MEKK homolog required for cell-wall assembly. MEKK required the downstream MAP kinase homolog in the BCK1-dependent pathway, demonstrating that it functionally replaces the BCK1 gene product (Bck1p) rather than bypassing the pathway. MEKK therefore selectively activates one of three distinct MAP kinase-dependent pathways. Possible explanations for this selectivity are discussed. Expression of the MEKK catalytic domain, but not the full-length molecule, corrected the cell-lysis defect of a pkc1 delta mutant that lacks a protein kinase C homolog that functions upstream of Bck1p. MEKK therefore functions downstream of the PKC1 gene product (Pkc1p). The N-terminal noncatalytic domain of MEKK, which contains several consensus protein kinase C phosphorylation sites, may, therefore, function as a negative regulatory domain. Protein kinase C phosphorylation may provide one mechanism for activating MEKK. PMID- 8197160 TI - A lymphokine, provisionally designated interleukin T and produced by a human adult T-cell leukemia line, stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. AB - In early phases of human T-cell lymphotrophic virus I-induced adult T-cell leukemia (ATL), the malignant cell proliferation is associated with an autocrine process involving coordinate expression of interleukin (IL) 2 and its receptor. However, during late-phase ATL, leukemic cells no longer produce IL-2 yet continue to express high-affinity IL-2 receptors. During studies to define pathogenic mechanisms that underlie this IL-2-independent proliferation, we demonstrated that the ATL cell line HuT-102 secretes a lymphokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Conditioned medium from HuT-102, when added to the IL-2-dependent CTLL-2 line, yielded a stimulation index of 230. Since CTLL-2 was purported to be IL-2-specific, we performed a number of studies to exclude IL 2 production by HuT-102. Stimulation of CTLL-2 cells by HuT-102-conditioned medium was not meaningfully inhibited by addition of an antiserum to IL-2. Furthermore, uninduced HuT-102 cells did not express mRNA encoding IL-2 as assessed by Northern blot analysis. No biological activity on CTLL-2 cells was mediated by purified IL-1, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12, IL 13, or granulocyte/macrophage colony-stimulating factor, thus differentiating these factors from IL-T. Based on preliminary biochemical data, IL-T is a protein with a pI value of 4.5 and a molecular mass in SDS gels of 14 kDa. In addition to its action on CTLL-2 cells, 3200-fold-purified IL-T stimulated proliferation of the human cytokine-dependent T-cell line Kit-225. Furthermore, addition of IL-T enhanced cytotoxic activity of large granular lymphocytes (i.e., induced lymphokine-activated killer cells). Thus, IL-T is a lymphokine that plays a role in T-cell proliferation and induction of lymphokine-activated killer cells. Furthermore, IL-T may contribute to IL-2-independent proliferation of select ATL cells and lines. PMID- 8197161 TI - The interleukin (IL) 2 receptor beta chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. AB - Late-phase human T-cell lymphotropic virus I-associated adult T-cell leukemia cells express IL-2 receptors (IL-2R) but no longer produce IL-2. We have reported that the IL-2-independent adult T-cell leukemia line HuT-102 secretes a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and lymphokine-activated killer cell activity. Stimulation of proliferation of the cytokine-dependent human T-cell line Kit-225 mediated by HuT-102-conditioned medium or by 3200-fold-purified IL-T was not blocked by the addition of antibodies against IL-2 or IL-2R alpha subunit. However, IL-T-mediated stimulation of this human T-cell line was inhibited by addition of Mik-beta 1, an antibody that binds specifically to IL-2R beta subunit. In addition, the activation of large granular lymphocytes to lymphokine-activated killer cells mediated by IL-T-containing conditioned medium was not blocked by antibodies directed toward IL-2 or IL-2 alpha but was inhibited by an antibody to IL-2R beta, suggesting the requirement of this receptor subunit for IL-T action. This conclusion was confirmed using an IL-3-dependent murine myeloid precursor cell line, 32D, that expresses IL-2R alpha and IL-2R gamma, but not IL-2R beta. Neither IL-2 nor IL-T stimulated 32D cell proliferation. However, after transfection with the gene encoding human IL-2R beta, 32D beta cells proliferated on addition of either cytokine. The IL-T-mediated stimulation of 32D beta proliferation was inhibited by an anti-IL-2R beta antibody but not by an anti-IL 2 antibody. Thus, the IL-T-mediated stimulation of T-cell and lymphokine activated killer cell activation requires the expression of the IL-2R beta subunit. PMID- 8197162 TI - Identification of the primary site of the human immunodeficiency virus type 1 RNA dimerization in vitro. AB - The diploid genome of all retroviruses is made of two homologous copies of RNA intimately associated near their 5' end, in a region called the dimer linkage structure. Dimerization of genomic RNA is thought to be important for crucial functions of the retroviral life cycle (reverse transcription, translation, encapsidation). Previous in vitro studies mapped the dimer linkage structure of human immunodeficiency virus type 1 (HIV-1) in a region downstream of the splice donor site, containing conserved purine tracts that were postulated to mediate dimerization, through purine quartets. However, we recently showed that dimerization of HIV-1 RNA also involves sequences upstream of the splice donor site. Here, we used chemical modification interference to identify nucleotides that are required in unmodified form for dimerization of a RNA fragment containing nucleotides 1-707 of HIV-1 RNA. These nucleotides map exclusively in a restricted area upstream of the splice donor site and downstream of the primer binding site. They are centered around a palindromic sequence (GUGCAC279) located in a hairpin loop. Our results support a model in which dimer formation is initiated by the annealing of the palindromic sequences, possibly by a loop-loop interaction between the two monomers. Further experiments show that the deletion of the stem-loop or base substitutions in the loop abolish dimerization, despite the presence of the previously postulated dimer linkage structure. On the other hand, deletions of the purine tracts downstream of the splice donor site do not prevent dimerization. Therefore, we conclude that the palindromic region represents the dimerization initiation site of genomic RNA. PMID- 8197163 TI - The fragile X syndrome d(CGG)n nucleotide repeats form a stable tetrahelical structure. AB - The fragile X mental retardation syndrome is associated with the expansion of trinucleotide 5'-d(CGG)-3' repeats within the FMR1 gene and with hypermethylation of the cytosine residues of these repeats. The expansion and hypermethylation may account for the suppression of the transcription of the FMR1 gene and for the delay of its replication during the cell cycle. Here we show that d(CGG)n oligomers can form a stable Hoogsteen-bonded structure that exhibits properties consistent with those of tetraplex DNA. Oligomers, d(mCGG)n, (n = 4, 5, or 7), at pH 8.0 and in the presence of an alkali metal ion form stable species exhibiting a reduced electrophoretic mobility in nondenaturing polyacrylamide gels. These species are denatured by heating at 90 degrees C for 10 min. With a short d(mCGG)5 oligomer, the slowly migrating species is formed only when the cytosine residue is 5-methylated, whereas with the longer d(CGG)7 it is generated whether or not cytosine is 5-methylated. By contrast, complementary cytosine-rich oligomers do not form analogous complexes. The second-order association kinetics of the formation of the slowly migrating species of d(mCGG)5 suggests that it is an interstrand complex. Formation of intermediate-size complexes between d(mCGG)5 and d(mCGG)7 indicates that the stoichiometry of the slowly migrating structures is tetramolecular. Protection of the complex from methylation by dimethyl sulfate indicates the involvement of the N-7 positions of the guanine residues in Hoogsteen hydrogen bonding, a characteristic of quadruplex structures. If formed in vivo along the expanded and hypermethylated d(mCGG)n stretch, this tetraplex structure could suppress transcription and replication of the FMR1 gene in the fragile X syndrome cells. PMID- 8197164 TI - Visualization of RNA tertiary structure by RNA-EDTA.Fe(II) autocleavage: analysis of tRNA(Phe) with uridine-EDTA.Fe(II) at position 47. AB - To test whether intramolecular autocleavage of RNA labeled at a single nucleotide position with EDTA.Fe(II) is a useful approach for the investigation of tertiary structures of RNAs, yeast phenylalanine tRNA was synthesized with uridine-EDTA (*U) at position U47. Autocleavage of [*U47]tRNA(Phe) in the presence of Fe(NH4)2(SO4)2 and dithiothreitol produced a set of cleavage fragments which are in general agreement with the three-dimensional structure derived from x-ray analysis. PMID- 8197165 TI - Wortmannin binds specifically to 1-phosphatidylinositol 3-kinase while inhibiting guanine nucleotide-binding protein-coupled receptor signaling in neutrophil leukocytes. AB - Wortmannin (WT) and its derivative 17-hydroxywortmannin (HWT) inhibit at nanomolar concentrations superoxide formation and exocytosis in neutrophils stimulated with chemotactic agonists. Treatment of neutrophils with radiolabeled [3H]HWT resulted in specific and saturable binding that paralleled the inhibition of the respiratory burst. Both half-maximal binding and half-maximal inhibition were observed at 5 nM, and > 90% of maximal binding and inhibition was observed at 20 nM HWT. Fluorography of subcellular fractions that were separated on NaDodSO4/PAGE showed that [3H]HWT binds covalently to a 110-kDa cytosolic protein. The WT-binding protein was purified from human neutrophils and bovine brain homogenates by column chromatography. The pure protein was eluted from gel filtration columns with an apparent molecular mass of 200 kDa and showed a heterodimeric structure on Coomassie-stained NaDodSO4/PAGE. In addition to the 110 kDa wortmannin binding protein an equally intense band was seen migrating at 85 kDa. This band was identified on Western blots as p85 alpha, the regulatory subunit of phosphatidylinositol (PI) 3-kinase (ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase, EC 2.7.1.137). The purified protein contained PI 3-kinase activity that was enriched > 20,000-fold from human neutrophil cytosol during preparation. The data impose a key role for PI 3-kinase-mediated signal transduction through guanine nucleotide-binding protein-coupled receptors and suggest that 3-phosphorylated inositol phospholipids are important second messengers for immediate responses in neutrophils. Furthermore, the results show that WT is a powerful and selective tool to study the function of PI 3-kinase. PMID- 8197166 TI - Ntk: a Csk-related protein-tyrosine kinase expressed in brain and T lymphocytes. AB - The activity of Src-related protein-tyrosine kinases is repressed by the phosphorylation of a conserved carboxyl-terminal tyrosine by another cytoplasmic protein-tyrosine kinase termed p50csk. In this study, we characterize Ntk, a protein-tyrosine kinase bearing striking similarities to p50csk. Like p50csk, Ntk possesses Src homology 3 and Src homology 2 domains and lacks the consensus tyrosine phosphorylation and myristoylation sites found in members of the Src family. Expression of ntk transcripts was maximal in brain, and was observed at significant levels in thymus and spleen. ntk RNA levels were dramatically reduced upon mitogenic stimulation of normal T lymphocytes and were minimal in transformed T-cell populations. Firm evidence that Ntk is a Csk-related enzyme was provided by the observation that it phosphorylated a Src-related polypeptide on the inhibitory carboxyl-terminal tyrosine. These findings indicate that Ntk is a Csk-related enzyme that may play an inhibitory role in the control of T-cell proliferation. PMID- 8197167 TI - Fundamental molecular differences between alcohol dehydrogenase classes. AB - Two types of alcohol dehydrogenase in separate protein families are the "medium chain" zinc enzymes (including the classical liver and yeast forms) and the "short-chain" enzymes (including the insect form). Although the medium-chain family has been characterized in prokaryotes and many eukaryotes (fungi, plants, cephalopods, and vertebrates), insects have seemed to possess only the short chain enzyme. We have now also characterized a medium-chain alcohol dehydrogenase in Drosophila. The enzyme is identical to insect octanol dehydrogenase. It is a typical class III alcohol dehydrogenase, similar to the corresponding human form (70% residue identity), with mostly the same residues involved in substrate and coenzyme interactions. Changes that do occur are conservative, but Phe-51 is of functional interest in relation to decreased coenzyme binding and increased overall activity. Extra residues versus the human enzyme near position 250 affect the coenzyme-binding domain. Enzymatic properties are similar--i.e., very low activity toward ethanol (Km beyond measurement) and high selectivity for formaldehyde/glutathione (S-hydroxymethylglutathione; kcat/Km = 160,000 min-1.mM 1). Between the present class III and the ethanol-active class I enzymes, however, patterns of variability differ greatly, highlighting fundamentally separate molecular properties of these two alcohol dehydrogenases, with class III resembling enzymes in general and class I showing high variation. The gene coding for the Drosophila class III enzyme produces an mRNA of about 1.36 kb that is present at all developmental stages of the fly, compatible with the constitutive nature of the vertebrate enzyme. Taken together, the results bridge a previously apparent gap in the distribution of medium-chain alcohol dehydrogenases and establish a strictly conserved class III enzyme, consistent with an important role for this enzyme in cellular metabolism. PMID- 8197168 TI - Id proteins control growth induction in mammalian cells. AB - Id1, Id2, and Id3 (HLH462) dimerize with members of the basic helix-loop-helix protein family, but due to the absence of the basic region, the resulting heterodimers cannot bind DNA. Therefore Id-type proteins negatively regulate DNA binding of the basic helix-loop-helix proteins. Here we report that Id1, Id2, and Id3 are induced shortly after serum stimulation in arrested NIH 3T3. Antisense oligonucleotides against the Id mRNAs delay the reentry of arrested cells into the cell cycle elicited by stimulation with serum or growth factors. Antisense oligonucleotides against all three Id mRNAs are more effective than individual ones. Combined, these results indicate that Id proteins are involved in the control of growth induction. PMID- 8197169 TI - The Caulobacter crescentus FlbD protein acts at ftr sequence elements both to activate and to repress transcription of cell cycle-regulated flagellar genes. AB - The flagellar genes (fla genes) in Caulobacter crescentus are organized into a regulatory hierarchy of four levels, I-IV, in which transcription of the class III and class IV genes late in the cell cycle from sigma 54-dependent promoters depends on expression of the class II genes above them. Timing of fla gene expression has been attributed to sequential activation and repression by specific transcription factors. Here we report that purified FlbD activates transcription in vitro from the sigma 54-dependent class III flbG promoter and repress transcription from the class II fliF promoter by binding to ftr (flagellar transcription regulator) sequence elements required for their transcriptional regulation in vivo. The FlbD protein makes symmetrical base specific contacts at three highly conserved guanine nucleotides in each half site of ftr1 and ftr1* at flbG and the single ftr4 site at fliF. The dual function of FlbD in activation of class III genes and repression of the class II fliF promoter is consistent with a central role of FlbD as a switch protein mediating the transition from level II to level III fla gene expression. PMID- 8197170 TI - The gene for the neuropeptide gonadotropin-releasing hormone is expressed in the mammary gland of lactating rats. AB - The high concentration of gonadotropin-releasing hormone (GnRH) in milk of several species implies that the mammary gland is either a site of synthesis for this neuropeptide or that it is efficiently concentrated from plasma by this organ. By PCR amplification of mammary gland cDNA, we have demonstrated expression of the mRNA for GnRH. The GnRH mRNA was present in the mammary gland of pregnant and lactating rats but not of virgin rats, implying that expression of the GnRH gene is activated during pregnancy, probably by prolactin. In contrast, actin mRNA was evident in all the preparations of mammary glands. Since GnRH is also known to be synthesized by the placenta, it is likely that the placenta and the mammary gland are complementary units by which the mother exercises control over the development and the metabolism of the infant during pregnancy as well as after parturition. In addition, GnRH synthesized by the mammary gland may also affect the mother by a paracrine and/or an endocrine mechanism. PMID- 8197171 TI - Down syndrome phenotypes: the consequences of chromosomal imbalance. AB - Down syndrome (DS) is a major cause of mental retardation and congenital heart disease. Besides a characteristic set of facial and physical features, DS is associated with congenital anomalies of the gastrointestinal tract, an increased risk of leukemia, immune system defects, and an Alzheimer-like dementia. Moreover, DS is a model for the study of human aneuploidy. Although usually caused by the presence of an extra chromosome 21, subsets of the phenotypic features of DS may be caused by the duplication of small regions of the chromosome. The physical map of chromosome 21 allows the molecular definition of the regions duplicated in these rare cases of partial trisomy. As a first step in identifying the genes responsible for individual DS features and their pathophysiology, a panel of cell lines derived from 16 such individuals has been established and the molecular break points have been determined using fluorescence in situ hybridization and Southern blot dosage analysis of 32 markers unique to human chromosome 21. Combining this information with detailed clinical evaluations of these patients, we have now constructed a "phenotypic map" that includes 25 features and assigns regions of 2-20 megabases as likely to contain the genes responsible. This study provides evidence for a significant contribution of genes outside the D21S55 region to the DS phenotypes, including the facies, microcephaly, short stature, hypotonia, abnormal dermatoglyphics, and mental retardation. This strongly suggests DS is a contiguous gene syndrome and augurs against a single DS chromosomal region responsible for most of the DS phenotypic features. PMID- 8197172 TI - Protein-tyrosine-phosphatase 2C is phosphorylated and inhibited by 44-kDa mitogen activated protein kinase. AB - Protein-tyrosine-phosphatase 2C (PTP2C, also named SHPTP2, SHPTP3, or PTP1D) is a cytosolic enzyme with two Src homology 2 domains. We have investigated its regulation by phosphorylation in PC12 rat pheochromocytoma cells. In untreated cells, PTP2C was phosphorylated predominantly on serine residues. A 5-min treatment with epidermal growth factor (EGF) induced an increase in phosphorylation on threonine and, to a lesser degree, on serine. After 45 min of exposure to EGF, PTP2C phosphorylation returned to basal levels. Using an in vitro kinase assay, we found that the 44-kDa mitogen-activated protein kinase, p44mapk, phosphorylated PTP2C on serine and threonine residues. This phosphorylation resulted in a pronounced inhibition of PTP2C enzyme activity measured with phosphorylated EGF receptors as substrate. Moreover, in intact PC12 cells, PTP2C was also inhibited following a short EGF treatment, but its activity returned to normal when the exposure to EGF was maintained for 45 min. The profile of this response to EGF can be inversely correlated to that of the stimulatory action of EGF on p44mapk. These data suggest that the EGF-induced regulation of PTP2C activity is mediated by p44mapk. These findings provide evidence for an additional role of the mitogen-activated protein kinase cascade- namely, the regulation of a PTP. PMID- 8197173 TI - Phorbol ester-induced expression, phosphorylation, and translocation of protein tyrosine-phosphatase 1C in HL-60 cells. AB - PTP1C, a protein-tyrosine-phosphatase (PTP) containing two Src homology 2 domains, is expressed at high levels in HL-60 human promyelocytic leukemia cells. It represents 0.15% of total protein in a postnuclear extract and corresponds to approximately 70% of phosphatase activity measured with p-nitrophenyl phosphate at pH 5.0. Upon differentiation of HL-60 cells to macrophages induced by phorbol 12-myristate 13-acetate (PMA), the activity and expression levels of PTP1C increase 2- to 3-fold. Furthermore, PTP1C is phosphorylated on serine residues upon PMA treatment. While the enzyme localizes entirely in the cytosolic fraction in untreated cells, 30-40% is found in a particulate fraction following differentiation. Immunofluorescent staining of differentiated cells before and after digitonin treatment indicates that the bound enzyme localizes on the plasma membrane. The time courses of induction and translocation of PTP1C correlate with the differentiation process. The PMA-induced differentiation is inhibited by sodium orthovanadate, suggesting the PTPs are required for this process. PMID- 8197174 TI - Specific association between the human DNA repair proteins XPA and ERCC1. AB - Processing of DNA damage by the nucleotide-excision repair pathway in eukaryotic cells is most likely accomplished by multiprotein complexes. However, the nature of these complexes and the details of the molecular interactions between DNA repair factors are for the most part unknown. Here, we demonstrate both in vivo, using the two-hybrid system, and in vitro, using recombinant proteins, that the human repair factors XPA and ERCC1 specifically interact. In addition, we report an initial determination of the domains in ERCC1 and XPA that mediate this interaction. These results suggest that XPA may play a role in the localization or loading of an incision complex, composed of ERCC1 and possibly other repair factors, onto a damaged site. PMID- 8197176 TI - Light-generated oligonucleotide arrays for rapid DNA sequence analysis. AB - In many areas of molecular biology there is a need to rapidly extract and analyze genetic information; however, current technologies for DNA sequence analysis are slow and labor intensive. We report here how modern photolithographic techniques can be used to facilitate sequence analysis by generating miniaturized arrays of densely packed oligonucleotide probes. These probe arrays, or DNA chips, can then be applied to parallel DNA hybridization analysis, directly yielding sequence information. In a preliminary experiment, a 1.28 x 1.28 cm array of 256 different octanucleotides was produced in 16 chemical reaction cycles, requiring 4 hr to complete. The hybridization pattern of fluorescently labeled oligonucleotide targets was then detected by epifluorescence microscopy. The fluorescence signals from complementary probes were 5-35 times stronger than those with single or double base-pair hybridization mismatches, demonstrating specificity in the identification of complementary sequences. This method should prove to be a powerful tool for rapid investigations in human genetics and diagnostics, pathogen detection, and DNA molecular recognition. PMID- 8197175 TI - Formation of a ternary complex by human XPA, ERCC1, and ERCC4(XPF) excision repair proteins. AB - The xeroderma pigmentosum complementation group A (XP-A) protein, XPA, has recently been expressed in Escherichia coli in a soluble and fully functional form. An affinity column was prepared by linking the XPA protein to a solid support. When HeLa cell-free extract capable of excision repair was applied to the column, > 99.9% of the proteins were in the flow-through. However, the flow through fraction lacked excision activity. The activity was restored by adding the high salt (1 M KCl) eluate of the column to the flow-through fraction. The XPA protein-bound fraction was tested for specific proteins by an in vitro complementation assay with a panel of cell-free extracts from DNA repair deficient human and rodent cell lines. The XPA-bound fraction complemented cell free extracts of excision repair cross-complementing 1 (ERCC-1), ERCC-4 (XP-F), and XP-A mutants. We conclude that the XPA damage recognition protein makes a ternary complex with the ERCC1/ERCC4(XPF) heterodimer with a potential nuclease function. PMID- 8197177 TI - An algorithm to generate low-resolution protein tertiary structures from knowledge of secondary structure. AB - An algorithm is described to assemble the three-dimensional fold of a protein starting from its secondary structure. A reduced representation of the polypeptide chain is used together with a crude potential based on pair hydrophobicities. The method is shown to be successful in locating the native topology for two 4-alpha-helix bundles, myohemerythrin and cytochrome b-562. PMID- 8197178 TI - Manual asymmetry and handedness. AB - Volumetric measurements show that right-handed individuals have larger right hands than left hands. In contrast, the hands of left-handers are much more nearly symmetrical. Based on what is known about trophic interactions between neurons and targets, these findings predict a corresponding asymmetry of the relevant parts of the sensorimotor system in right-handers. The lack of an opposite-hand asymmetry among left-handers further implies that right- and left handed phenotypes do not arise according to the same developmental rules. PMID- 8197179 TI - A measure for brain complexity: relating functional segregation and integration in the nervous system. AB - In brains of higher vertebrates, the functional segregation of local areas that differ in their anatomy and physiology contrasts sharply with their global integration during perception and behavior. In this paper, we introduce a measure, called neural complexity (CN), that captures the interplay between these two fundamental aspects of brain organization. We express functional segregation within a neural system in terms of the relative statistical independence of small subsets of the system and functional integration in terms of significant deviations from independence of large subsets. CN is then obtained from estimates of the average deviation from statistical independence for subsets of increasing size. CN is shown to be high when functional segregation coexists with integration and to be low when the components of a system are either completely independent (segregated) or completely dependent (integrated). We apply this complexity measure in computer simulations of cortical areas to examine how some basic principles of neuroanatomical organization constrain brain dynamics. We show that the connectivity patterns of the cerebral cortex, such as a high density of connections, strong local connectivity organizing cells into neuronal groups, patchiness in the connectivity among neuronal groups, and prevalent reciprocal connections, are associated with high values of CN. The approach outlined here may prove useful in analyzing complexity in other biological domains such as gene regulation and embryogenesis. PMID- 8197180 TI - Light induces rapid changes of the phosphorylation pattern in the cytosol of evacuolated parsley protoplasts. AB - The fractionation of cells of a parsley suspension culture [Petroselinum crispum (Mill.) A. Hill] by protoplasting and subsequent removal of the vacuoles led to physiologically intact evacuolated protoplasts retaining light inducibility of chalcone synthase expression. Lysis of the evacuolated protoplasts permitted the isolation of a pure, highly concentrated cytosolic fraction containing major cytosolic membranes but only minor contamination by proplastids, mitochondria, and nuclei. Short-time irradiations of the cytosol with red or UV-containing white light resulted in very fast changes of the phosphorylation pattern of 18-, 40-, 48-, 55- to 70-, and 120-kDa proteins. Major differences were observed between the phosphorylation patterns obtained by red or UV-containing white light treatment, indicating a different primary action of the excited photoreceptors in vitro. Separation of the microsomal fraction from the cytosolic matrix established the localization of these proteins. Chase and photoreversibility experiments revealed that phytochrome in vitro regulates the phosphorylation of the 40-kDa protein by modifying a soluble cytosolic kinase/phosphatase system. PMID- 8197181 TI - Zero-shift tuning in geonium by variation of trapped charge. AB - Measuring the g factor, or gyromagnetic ratio of an individual electron or positron permanently confined in ultrahigh vacuum at liquid helium temperature, provides one of the few avenues for testing the currently accepted standard model that views these elementary particles, on the same level as the quarks, as point like objects without internal structure. Our results, even though their error limits are the smallest ever attained, would still benefit by possibly two orders of magnitude if a shift, estimated at 4 parts in 10(12), caused by interaction of the cyclotron motion with standing electromagnetic waves in the trap cavity confining the electron could be eliminated. Reexamination of experimental data obtained in another connection suggests that it is practical to identify certain critical cyclotron frequency values for that the shift disappears by testing if the cyclotron frequency measured on a cloud of electrons does not vary with the number of electrons it contains. Clouds here must be kept very much smaller than the wavelength of the above standing waves. PMID- 8197182 TI - Molecular interactions between interferon consensus sequence binding protein and members of the interferon regulatory factor family. AB - Interferon (IFN) consensus sequence binding protein (ICSBP) is a transcription factor expressed mostly in the cells of the immune system. ICSBP belongs to the IFN regulatory factor (IRF) family, which also includes IRF-1, IRF-2, and the IFN alpha-stimulated gene factor 3 gamma (ISGF3 gamma). We show here that ICSBP forms a complex with IRF-1 or IRF-2 both in vivo and in vitro and, in the presence or absence of the target DNA, with the IFN-stimulated response element (ISRE). Further, electrophoretic mobility shift assays show that this interaction greatly enhances the otherwise very low binding affinity of ICSBP to the ISRE. We show, on the other hand, that ICSBP inhibits binding of the IFN-alpha-stimulated gene factor 3 gamma to the ISRE. Through these interactions ICSBP is likely to exert complex modulatory functions in the regulation of IFN-stimulated genes. PMID- 8197183 TI - Molecular cloning of the gene encoding the mouse parathyroid hormone/parathyroid hormone-related peptide receptor. AB - The parathyroid hormone/parathyroid hormone-related peptide receptor (PTHR) is a G-protein-coupled receptor containing seven predicted transmembrane domains. We have isolated and characterized recombinant bacteriophage lambda EMBL3 genomic clones containing the mouse PTHR gene, including 10 kilobases of the promoter region. The gene spans > 32 kilobases and is divided into 15 exons, 8 of which contain the transmembrane domains. The PTHR exons containing the predicted membrane-spanning domains are heterogeneous in length and three of the exon intron boundaries fall within putative transmembrane sequences, suggesting that the exons did not arise from duplication events. This arrangement is closely related to that of the growth hormone releasing factor receptor gene, particularly in the transmembrane region, providing strong evidence that the two genes evolved from a common precursor. Transcription is initiated principally at a series of sites over a 15-base-pair region. The proximal promoter region is highly (G+C)-rich and lacks an apparent TATA box or initiator element homologies but does contain CCGCCC motifs. The presumptive amino acid sequence of the encoded receptor is 99%, 91%, and 76% identical to those of the rat, human, and opossum receptors, respectively. There is no consensus polyadenylation signal in the 3' untranslated region. The poly(A) tail of the PTHR transcript begins 32 bases downstream of a 35-base-long A-rich sequence, suggesting that this region directs polyadenylylation. PMID- 8197184 TI - Qualitative changes in the subunit composition of kappa B-binding complexes during murine B-cell differentiation. AB - We report here that the major kappa B-binding complex in murine mature B cells is composed of a p50-Rel heterodimer, whereas the major inducible form in pre-B cells is a p50-p65 heterodimer. Treatment of a pre-B-cell line with lipopolysaccharide changes the subunit composition of kappa B-binding complexes from p50-p65 to p50-Rel. This change is preceded by the enhanced Rel expression and correlates with the expression of the gene for the immunoglobin kappa light chain. The heterodimeric p50-Rel complex binds to the intronic enhancer-kappa B site in the immunoglobulin kappa light chain gene at least 20-fold more stably than does the p50-p65 dimer. These data support a model in which augmentation of Rel expression during the differentiation of pre-B cells to mature B cells leads to an exchange of kappa B-binding subunits resulting in the transcriptional activation of the gene for the immunoglobulin kappa light chain. PMID- 8197185 TI - Rab5a is a common component of the apical and basolateral endocytic machinery in polarized epithelial cells. AB - In nonpolarized cells, the small GTPase Rab5a is localized to the plasma membrane, clathrin-coated vesicles, and early endosomes. Rab5a is required for early endosome fusion in vitro and regulates transport between the plasma membrane and early endosomes, in vivo. In polarized epithelial cells endocytosis occurs from separate apical and basolateral plasma membrane domains. Internalized molecules are initially delivered to distinct apical or basolateral early endosomes. In vitro, apical early endosomes can readily fuse with one another but not with the basolateral endosomes and vice versa, thereby indicating that the apical and basolateral early endocytic pathways are controlled by distinct machineries. Here, we have investigated the localization and function of Rab5a in polarized epithelial cells. Confocal immunofluorescence microscopy on mouse kidney sections revealed association of the protein with the apical and basolateral plasma membrane domains and underlying structures. In polarized Madin Darby canine kidney I cells, endogenous and overexpressed Rab5a have the same distribution. Moreover, overexpression of the protein causes a 2-fold increase in fluid-phase uptake from both domains of the cell, thus showing that Rab5a functions in apical and basolateral endocytosis. Our data indicate that the apical and basolateral endocytic machineries of epithelial cells share common regulatory components and that Rab5a per se is not sufficient to target endocytic vesicles to apical or basolateral early endosomes. PMID- 8197186 TI - Cytonuclear genetics of experimental fish hybrid zones inside Biosphere 2. AB - Two species of mosquitofish (family Poeciliidae) known to hybridize in nature were introduced into freshwater habitats inside Biosphere 2, and their population genetics were monitored after 2 years. Within four to six generations, nuclear and cytoplasmic markers characteristic of Gambusia holbrooki had risen greatly in frequency, although some Gambusia affinis alleles and haplotypes were retained primarily in recombinant genotypes, indicative of introgressive hybridization. The temporal cytonuclear dynamics proved similar to population genetic changes observed in replicated experimental hybrid populations outside of Biosphere 2, thus indicating strong directional selection favoring G. holbrooki genotypes across the range of environments monitored. When interpreted in the context of species-specific population demographies observed previously, results suggest that the extremely rapid evolution in these zones of secondary contact is attributable primarily to species differences in life-history traits. PMID- 8197187 TI - Mice lacking alpha 1 (IX) collagen develop noninflammatory degenerative joint disease. AB - Type IX collagen is a nonfibrillar collagen composed of three gene products, alpha 1(IX), alpha 2(IX), and alpha 3(IX). Type IX molecules are localized on the surface of type II-containing fibrils and consist of two arms, a long arm that is crosslinked to type II collagen and a short arm that projects into the perifibrillar space. In hyaline cartilage, the alpha 1(IX) collagen transcript encodes a polypeptide with a large N-terminal globular domain (NC4), whereas in many other tissues an alternative transcript encodes an alpha 1(IX) chain with a truncated NC4 domain. It has been proposed that type IX molecules are involved in the interaction of fibrils with each other or with other components of the extracellular matrix. To test this hypothesis, we have generated a mouse strain lacking both isoforms of the alpha 1(IX) chain. Homozygous mutant mice are viable and show no detectable abnormalities at birth but develop a severe degenerative joint disease resembling human osteoarthritis. PMID- 8197188 TI - Potent inhibition of human immunodeficiency virus type 1 replication by an intracellular anti-Rev single-chain antibody. AB - Human immunodeficiency virus type 1 (HIV-1) has a complex life cycle, which has made it a difficult target for conventional therapeutic modalities. A single chain antibody moiety, directed against the HIV-1 regulatory protein Rev, which rescues unspliced viral RNA from the nucleus of infected cells, has now been developed. This anti-Rev single-chain construct (SFv) consists of both light and heavy chain variable regions of anti-Rev monoclonal antibody, which, when expressed intracellularly within human cells, potently inhibits HIV-1 replication. This intracellular SFv molecule is demonstrated to specifically antagonize Rev function. Thus, intracellular SFv expression, against a retroviral regulatory protein, may be useful as a gene therapeutic approach to combat HIV-1 infections. PMID- 8197189 TI - Nuclear transformation of Volvox carteri. AB - Stable nuclear transformation of Volvox carteri was achieved using the cloned V. carteri nitA+ gene (which encodes nitrate reductase) to complement a nitA- mutation. Following bombardment of mutant cells with plasmid-coated gold particles, putative transformants able to utilize nitrate as a nitrogen source were recovered with an efficiency of approximately 2.5 x 10(5). DNA analysis indicated that the plasmid integrated into the genome, often in multiple copies, at sites other than the nitA locus. Cotransformants were recovered with a frequency of 40-80% when cells were cobombarded with a selected and an unselected marker. Thus, V. carteri becomes one of the simplest multicellular organisms that is accessible to detailed molecular studies of genes regulating cellular differentiation and morphogenesis. PMID- 8197190 TI - Mitochondrial creatine kinase: a major constituent of pathological inclusions seen in mitochondrial myopathies. AB - Overaccumulation of abnormally organized mitochondria in so-called "ragged-red" skeletal muscle fibers is a morphological hallmark of mitochondrial myopathies, in particular of mitochondrial encephalomyopathies. Characteristic for the abnormal mitochondria is the occurrence of highly ordered crystalline inclusions. Immuno-electron microscopy revealed that these inclusions react heavily with specific antibodies against mitochondrial creatine kinase (Mi-CK). Image processing of selected crystalline inclusions, sectioned along the crystallographic b, c planes, resulted in an averaged picture displaying an arrangement of regular, square-shaped particles with a central cavity. The overall appearance, dimensions, and symmetry of these building blocks are very reminiscent of single isolated Mi-CK octamers. Taking these findings together, it is concluded that Mi-CK octamers indeed represent the major, if not the only, component of these mitochondrial inclusions. PMID- 8197191 TI - Prostaglandin E2 elicits a morphological change in cultured orbital fibroblasts from patients with Graves ophthalmopathy. AB - Fibroblasts derived from distinct anatomical regions appear to differ in regard to their behavior in culture. These differences may reflect functions of these cells in vivo that are tissue specific. Moreover, intrinsic differences in fibroblasts may underlie the site-specific connective tissue manifestations associated with systemic disease. We have demonstrated previously that orbital fibroblasts exhibit different cytokine response domains and protein synthetic programs when compared to those emanating from the skin. In the present communication, we demonstrate that prostaglandin E2 (PGE2) elicits in cultured human orbital fibroblasts from patients with Graves ophthalmopathy a rapid and dramatic change in cell morphology in vitro as assessed by phase-contrast and scanning electron microscopy. The central areas of the cells become elevated with respect to the plane of the substratum and are stellate, with long processes that touch neighboring cells. These changes occur within 6 hr of prostanoid addition to culture medium at an apparent concentration threshold of approximately 10 nM. Shape changes are accompanied by marked alterations in monolayer impedance as assessed by electric cell-substrate impedance sensing as described previously. Both morphologic and impedance changes elicited by PGE2 revert over 24 hr toward those found in untreated cells despite the continued presence of the prostanoid in the culture medium. In contrast, dermal fibroblasts fail to respond to PGE2. These observations define a previously unrecognized phenotypic attribute of orbital fibroblasts. Intrinsic differences in these cells may account for the anatomic site-selective vulnerability of the orbit in Graves ophthalmopathy. The culture system described here may be useful for studying the morphogenic actions of prostanoids. PMID- 8197192 TI - Bacterial genes involved in incorporation of nickel into a hydrogenase enzyme. AB - Nickel is an essential component of all H2-uptake hydrogenases. A fragment of DNA that complements a H2-uptake-deficient but nickel-cured mutant strain (JHK7) of Bradyrhizobium japonicum was isolated and sequenced. This 4.5-kb DNA fragment contains four open reading frames designated as ORF1, hupN, hupO, and hupP, which encode polypeptides with predicted masses of 17, 40, 19, and 63.5 kDa, respectively. The last three open reading frames (hupNOP) are most likely organized as an operon with a putative sigma 54-type promoter. Based on its hydropathy profile, HupN is predicted to be a transmembrane protein. It has 56% identity to the previously described HoxN (high-affinity nickel transport protein) of Alcaligenes eutrophus. A subclone (pJF23) containing the hupNOP genes excluding ORF1 completely complemented (in trans) strain JHK7 for hydrogenase activity in low nickel conditions. pJF26 containing only a functional hupN complemented the hydrogenase activity of mutant strain JHK7 to 30-55% of the wild type level. Mutant strain JHK70, with a chromosomal deletion in hupP but with an intact hupNO, showed greater activities than pJF26-complemented JHK7 but still had lower activities than the wild type at all nickel levels tested. pJF25, containing the entire hupO and hupP, but without hupN (a portion of hupN was deleted), did not complement hydrogenase activity of mutant strain JHK7. The results suggest that the products of the hupNOP operon are all involved in nickel incorporation/metabolism into the hydrogenase apoprotein. Based on (previous) nickel transport studies of strain JHK7, the hupNOP genes appear not to be involved in nickel transport by whole cells. The deleterious effects on hydrogenase expression are most pronounced by lack of the HupN product. PMID- 8197193 TI - Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat. AB - The trophism of brain-derived neurotrophic factor (BDNF) for dopaminergic cells in culture has led to significant interest in the role of BDNF in the etiology and potential treatment of Parkinson disease. Previous in vivo investigation of BDNF delivery to axotomized substantia nigra dopaminergic neurons in the adult rat has shown no protective effect. In this study, we produced nigral degeneration by infusing 1-methyl-4-phenylpyridinium (MPP+), a mitochondrial complex I inhibitor and the active metabolite of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), into the rat striatum. The subsequent loss of nigral neurons was presumably due to mitochondrial toxicity after MPP+ uptake and retrograde transport to the substantia nigra. We engineered immortalized rat fibroblasts to secrete human BDNF and implanted these cells near the substantia nigra 7 days before striatal MPP+ infusion. We found that BDNF-secreting fibroblasts markedly increased nigral dopaminergic neuronal survival when compared to control fibroblast implants. The observation that BDNF prevents MPTP induced dopaminergic neuronal degeneration in the adult brain has significance for the treatment of neurodegenerative disorders, which may involve mitochondrial dysfunction, such as Parkinson disease. PMID- 8197194 TI - Crystal structure of CspA, the major cold shock protein of Escherichia coli. AB - The major cold shock protein of Escherichia coli, CspA, produced upon a rapid downshift in growth temperature, is involved in the transcriptional regulation of at least two genes. The protein shares high homology with the nucleic acid binding domain of the Y-box factors, a family of eukaryotic proteins involved in transcriptional and translational regulation. The crystal structure of CspA has been determined at 2-A resolution and refined to R = 0.187. CspA is composed of five antiparallel beta-strands forming a closed five-stranded beta-barrel. The three-dimensional structure of CspA is similar to that of the major cold shock protein of Bacillus subtilis, CspB, which has recently been determined at 2.45-A resolution. However, in contrast to CspB, no dimer is formed in the crystal. The surface of CspA is characteristic for a protein interacting with single-stranded nucleic acids. Due to the high homology of the bacterial cold shock proteins with the Y-box factors, E. coli CspA and B. subtilis CspB define a structural framework for the common cold shock domain. PMID- 8197195 TI - The human Ha-ras oncogene induces genomic instability in murine fibroblasts within one cell cycle. AB - Many human tumors contain an activating mutation in one of the ras protooncogenes. Additionally, these tumor cells are often heteroploid and characterized by chromosome breaks and rearrangements that are consequences of the genomic instability that is thought to contribute to tumor progression. The concurrence of ras mutations and genomic instability in tumors prompted us to ask whether selective induction of an activated Ha-ras gene could render a genome unstable. The NIH 3T3 cells used in this study contained mutant p53 genes and carried a selectively inducible activated (EJ) Ha-ras transgene under the control of bacterial lactose regulatory elements. When stably transfected cells were induced to express activated Ha-ras by isopropyl beta-D-thiogalactoside administration, there was a marked increase in the number of gross chromosomal aberrations including acentric fragments, multicentric chromosomes, and double minutes, which occurred within the time frame of a single cell cycle from the time of induction. To confirm that these aberrations occurred within the first cell cycle after mutant Ha-ras induction, the cells were arrested in G1 phase by serum depletion and, subsequently, released by administration of isopropyl beta-D thiogalactoside or serum. The mitoses from cells released with isopropyl beta-D thiogalactoside contained a 3-fold elevation in the fraction of chromosomes containing aberrations compared to mitoses from parallel cell cultures that were released with serum. Thus, the induction of activated Ha-ras gene expression in these cells results in genomic instability that can be detected as aberrant chromosomes at the next mitosis. PMID- 8197196 TI - Columbines: a geographically widespread species flock. AB - Species in the columbine genus, Aquilegia, are known for their broad variation in ecology and floral morphology. Aquilegia is also known for the large degree of intercompatibility among its species, which has led to the suggestion that the genus has arisen recently. However, intercompatibility does not always imply recent divergence and the widespread distribution pattern of the genus has suggested an older age. We constructed phylogenies for Aquilegia plus its close relatives by using nucleotide sequence data from both nuclear and chloroplast DNA. The sequence data averaged over 1250 bp per species. Among the 14 columbine species sampled from Europe, Asia, and North America only 16-bp changes and one insertion/deletion event were detected. In contrast, related genera had from 3 to 45 times this level of variation. The phylogenies derived from the chloroplast and nuclear DNA sequences were highly concordant and suggest that the columbines are the result of a recent, rapid radiation. In contrast to other examples of species flocks, Aquilegia has radiated on a widespread geographical scale. By comparison with their related taxa, we suggest that the evolution of the nectar spur in Aquilegia was a key innovation for this genus and allowed rapid speciation through specialization to specific pollinators. PMID- 8197197 TI - DNA fingerprinting analysis of parent-offspring conflict in a bee. AB - Demonstrating the importance of haplodiploidy in the evolution of eusociality among the Hymenoptera (bees, wasps, and ants) requires estimation of four parameters: relatedness between cooperating individuals, effective mating frequency, sex ratio, and rates of worker reproduction. Multilocus DNA fingerprinting techniques permitted the precise determination of these parameters for the primitively eusocial bee Augochlorella striata (Halictidae). DNA fingerprints revealed an unprecedented resolution of genetic relationships within colonies, detecting factors such as intraspecific nest parasitism and diploid males that confounded estimates of relatedness and sex ratio, respectively. Parameter estimates (i) corroborate recent evidence for queen-worker conflict over the sex ratio and (ii) implicate the role of haplodiploidy in the evolution of worker behavior. PMID- 8197198 TI - In vivo production of human factor VII in mice after intrasplenic implantation of primary fibroblasts transfected by receptor-mediated, adenovirus-augmented gene delivery. AB - Hemophilia A is caused by defects in the factor VIII gene. This results in life threatening hemorrhages and severe arthropathies. Today, hemophiliacs are treated with human blood-derived factor VIII. In the future, it may be possible to use gene therapy to avoid long-term complications of conventional therapy and to improve the quality of life. However, initial gene therapy models using retroviral vectors and nonviral gene transfer techniques to introduce factor VIII gene constructs have been hampered by low expression levels of factor VIII. We show here that high expression levels of the B-domain-deleted human factor VIII in primary mouse fibroblasts and myoblasts are obtained by using receptor mediated, adenovirus-augmented gene delivery (transferrinfection). We demonstrate that, presumably owing to the high molecular weight of factor VIII or its metabolic instability, secretion into the blood and attainment of therapeutic in vivo levels of factor VIII is achieved only if transfected autologous primary fibroblasts or myoblasts are delivered to the liver or spleen, but not if myoblasts are implanted into muscle, a strategy known to be successful for factor IX delivery. PMID- 8197199 TI - Natural sleep modifies the rat electroretinogram. AB - We show here electroretinograms (ERGs) recorded from freely moving rats during sleep and wakefulness. Bilateral ERGs were evoked by flashes delivered through a light-emitting diode implanted under the skin above one eye and recorded through electrodes inside each orbit near the optic nerve. Additional electrodes over each visual cortex monitored the brain waves and collected flash-evoked cortical potentials to compare with the ERGs. Connections to the stimulating and recording instruments through a plug on the head made data collection possible at any time without physically disturbing the animal. The three major findings are (i) the ERG amplitude during slow-wave sleep can be 2 or more times that of the waking response; (ii) the ERG patterns in slow-wave and REM sleep are different; and (iii) the sleep-related ERG changes closely mimic those taking place at the same time in the responses evoked from the visual cortex. We conclude that the mechanisms that alter the visual cortical-evoked responses during sleep operate also and similarly at the retinal level. PMID- 8197200 TI - Cloning, expression, and localization of a chloride-facilitated, cocaine sensitive serotonin transporter from Drosophila melanogaster. AB - We report here on the isolation and characterization of a serotonin (5HT) transporter from Drosophila melanogaster. A 3.1-kb complementary DNA clone (dSERT) was found to encode a protein of 622 amino acid residues with a predicted molecular mass of approximately 69 kDa and a putative transmembrane topology characteristic of cloned members of the mammalian Na+/Cl- neurotransmitter cotransporter gene family. dSERT displays highest overall amino acid sequence identity with the mammalian 5HT (51%), norepinephrine (47%), and dopamine (47%) transporters and shares with all transporters 104 absolutely conserved amino acid residues. Upon transient expression in HeLa cells, dSERT exhibited saturable, high-affinity, and sodium-dependent [3H]5HT uptake with estimated Km and Vmax values of approximately 500 nM and 5.2 x 10(-18) mol per cell per min, respectively. In marked contrast to the human SERT (hSERT), 5HT-mediated transport by dSERT was not absolutely dependent on extracellular Cl-, while the sodium-dependent uptake of 5HT was facilitated by increased extracellular Cl- concentrations. dSERT displays a pharmacological profile and rank order of potency consistent with, but not identical to, mammalian 5HT transporters. Comparison of the affinities of various compounds for the inhibition of 5HT transport by both dSERT and hSERT revealed that antidepressants were 3- to 300 fold less potent on dSERT than on hSERT, while mazindol displayed approximately 30-fold greater potency for dSERT. Both cocaine and RTI-55 inhibited 5HT uptake by dSERT with estimated inhibition constants of approximately 500 nM, while high concentrations (> 10 microM) of dopamine, norepinephrine, octopamine, tyramine, and histamine failed to inhibit transport. In situ hybridization reveals the selective expression of dSERT mRNA to specific cell bodies in the ventral ganglion of the embryonic and larval Drosophila nervous system with a distribution pattern virtually identical to that of 5HT-containing neurons. The dSERT gene was mapped to position 60C on chromosome 2. The availability of the gene encoding the unique ion dependence and pharmacological characteristics of dSERT may allow for identification of those amino acid residues and structural motifs that confer the pharmacologic specificity and genetic regulation of the 5HT transport process. PMID- 8197201 TI - Chloroplast and nuclear gene sequences indicate late Pennsylvanian time for the last common ancestor of extant seed plants. AB - We have estimated the time for the last common ancestor of extant seed plants by using molecular clocks constructed from the sequences of the chloroplastic gene coding for the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (rbcL) and the nuclear gene coding for the small subunit of rRNA (Rrn18). Phylogenetic analyses of nucleotide sequences indicated that the earliest divergence of extant seed plants is likely represented by a split between conifer cycad and angiosperm lineages. Relative-rate tests were used to assess homogeneity of substitution rates among lineages, and annual angiosperms were found to evolve at a faster rate than other taxa for rbcL and, thus, these sequences were excluded from construction of molecular clocks. Five distinct molecular clocks were calibrated using substitution rates for the two genes and four divergence times based on fossil and published molecular clock estimates. The five estimated times for the last common ancestor of extant seed plants were in agreement with one another, with an average of 285 million years and a range of 275-290 million years. This implies a substantially more recent ancestor of all extant seed plants than suggested by some theories of plant evolution. PMID- 8197202 TI - Arrest of Listeria movement in host cells by a bacterial ActA analogue: implications for actin-based motility. AB - Upon entering the host cell's cytoplasm, the pathogen Listeria monocytogenes can subvert the normal contractile system of the host cell; subsequent assembly of polar actin-filament structures is likely to provide the force for rapid intracellular bacterial movement and its cell-to-cell spread. We have now investigated the functional consequences of microinjecting Listeria-infected PtK2 cells with a synthetic peptide, CFEFPPPPTDE. This peptide represents one of four related oligoproline stretches in ActA, a bacterial surface protein necessary for Listeria-induced actin assembly. Over an estimated intracellular concentration range of 80 nM to 0.8 microM, this analogue rapidly blocks the formation of the actin-filament tails and arrests intracellular bacterial motility. Over the same time scale and concentration range, introduction of the ActA analogue also causes host cell membrane retraction. Bodipyphallacidin staining reveals that microinjection of the ActA analogue results in massive retraction of the actin cytoskeleton. Microinjection of 1-20 microM poly(L-proline) (intracellular concentration) fails to block Listeria intracellular movement or polar actin filament assembly. As observed with ActA, however, poly(L-proline) does cause membrane retraction. Our findings demonstrate the efficacy of low molecular weight peptides in efforts to distinguish mechanistic features in Listeria motility and PtK2 host cell membrane reorganization. These observations also suggest that a cytoskeletal component sensitive to specific oligoproline peptides may participate in protein-protein interactions essential for both of these actin associated processes. PMID- 8197203 TI - DNA sequence support for a close phylogenetic relationship between some storks and New World vultures. AB - Nucleotide sequences from the mitochondrial cytochrome b gene were used to address a controversial suggestion that New World vultures are related more closely to storks than to Old World vultures. Phylogenetic analyses of 1-kb sequences from 18 relevant avian species indicate that the similarities in morphology and behavior between New World and Old World vultures probably manifest convergent adaptations associated with carrion-feeding, rather than propinquity of descent. Direct sequence evidence for a close phylogenetic alliance between at least some New World vultures and storks lends support to conclusions reached previously from DNA.DNA hybridization methods and detailed morphology-based appraisals, and it illustrates how mistaken assumptions of homology for organismal adaptations can compromise biological classifications. However, there was a lack of significant resolution for most other branches in the cytochrome b phylogenetic reconstructions. This irresolution is most likely attributable to a close temporal clustering of nodes, rather than to ceiling effects (mutational saturation) producing an inappropriate window of resolution for the cytochrome b sequences. PMID- 8197204 TI - Chemical synthesis of a fully active transcriptional repressor protein. AB - Plasmid pLS1-encoded 45-amino acid transcriptional repressor CopG (formerly RepA) has been chemically synthesized. A one-step purification of the synthetic protein has been developed, which yields high levels of pure protein with low or no contamination of truncated products. We have compared some properties of the chemical CopG protein with those of the biologically purified CopG. The two proteins were indistinguishable in (i) their ability to generate specific protein DNA complexes, (ii) their capacity to protect a restriction site included within the CopG DNA target, and (iii) in their in vitro capacity to specifically repress synthesis of copG mRNA. PMID- 8197205 TI - X-ray structure of a cyclophilin B/cyclosporin complex: comparison with cyclophilin A and delineation of its calcineurin-binding domain. AB - The crystal structure of a complex between recombinant human cyclophilin B (CypB) and a cyclosporin A (CsA) analog has been determined and refined at 1.85-A resolution to a crystallographic R factor of 16.0%. The overall structures of CypB and of cyclophilin A (CypA) are similar; however, significant differences occur in two loops and at the N and C termini. The CsA-binding pocket in CypB has the same structure as in CypA and cyclosporin shows a similar bound conformation and network of interactions in both CypB and CypA complexes. The network of the water-mediated contacts is also essentially conserved. The higher potency of the CypB/CsA complex versus CypA/CsA in inhibiting the Ca(2+)- and calmodulin dependent protein phosphatase calcineurin is discussed in terms of the structural differences between the two complexes. The three residues Arg90, Lys113, and Ala128 and the loop containing Arg158 on the surface of CypB are likely to modulate the differences in calcineurin inhibition between CypA and CypB. PMID- 8197206 TI - Synthetic fibronectin peptides interrupt inflammatory cell infiltration in transforming growth factor beta 1 knockout mice. AB - Pronounced mononuclear leukocyte (MNL) infiltration occurs in multiple organs of mice homozygous for a transforming growth factor beta 1 (TGF-beta 1) loss-of function gene mutation [TGF-beta 1 (-/-)], followed by cachexia and eventually death. Consistent with the increased leukocyte adhesion and tissue infiltration, MNLs isolated from spleen, thymus, and peripheral blood of symptomatic TGF-beta 1 (-/-) mice, as compared to littermate controls, exhibited increased adhesion to extracellular matrix proteins and to endothelial cells in vitro. Incubation of TGF-beta 1 (-/-) MNLs with selected synthetic peptides corresponding to cell- and heparin-binding sequences of fibronectin (FN) significantly attenuated adhesion of these cells not only to FN but also to endothelial cells in vitro. Based on these observations, mice were treated with the FN peptides in an attempt to rescue them from tissue inflammation and cardiopulmonary failure. Daily injections of a combination of four synthetic FN peptides that interact with beta 1-integrins and/or cell surface proteoglycans blocked the massive infiltration of MNLs into the heart and lungs of TGF-beta 1 (-/-) mice. Peptide treatment initiated on day 8, coincident with the first evidence of increased leukocyte endothelial cell interactions, not only blocked tissue infiltration but also moderated the lethal wasting syndrome. PMID- 8197207 TI - Neurovirulent strains of Alphavirus induce apoptosis in bcl-2-expressing cells: role of a single amino acid change in the E2 glycoprotein. AB - The isolation and sequence comparison of avirulent and neurovirulent strains of polio virus, alpha virus, herpes virus, immunodeficiency virus, and other viruses have identified genetic changes that are required to cause disease in the nervous system. The molecular mechanisms by which these genetic changes result in neurovirulence are unknown. An avirulent laboratory strain of the Alphavirus Sindbis kills most cultured cell lines not by lethal parasitism, but by inducing apoptosis or programmed cell death. Transfection of cultured cells with the human bcl-2 oncogene can block Sindbis virus-induced apoptosis, resulting in a persistent viral infection resembling that observed in brains of immunodeficient mice. We investigated the possibility that neurovirulent strains of Sindbis virus could overcome the protective effects of bcl-2--a potential mechanism to explain the ability of these strains to cause fatal disease. Strains of Sindbis virus that were lethal for 2- to 4-week-old mice induced apoptotic death in cultured cells despite the presence of bcl-2. Using recombinant viruses, we show that a single amino acid change in the E2 glycoprotein of Sindbis virus confers both neurovirulence and the ability to kill cells expressing bcl-2. PMID- 8197209 TI - An example that is better ignored. PMID- 8197208 TI - Calcium transients in dendrites of neocortical neurons evoked by single subthreshold excitatory postsynaptic potentials via low-voltage-activated calcium channels. AB - Simultaneous recordings of membrane voltage and concentration of intracellular Ca2+ ([Ca2+]i) were made in apical dendrites of layer 5 pyramidal cells of rat neocortex after filling dendrites with the fluorescent Ca2+ indicator Calcium Green-1. Subthreshold excitatory postsynaptic potentials (EP-SPs), mediated by the activation of glutamate receptor channels, caused a brief increase in dendritic [Ca2+]i. This rise in dendritic [Ca2+]i was mediated by the opening of low-voltage-activated Ca2+ channels in the dendritic membrane. The results provide direct evidence that dendrites do not function as passive cables even at low-frequency synaptic activity; rather, a single subthreshold EPSP changes the dendritic membrane conductance by opening Ca2+ channels and generating a [Ca2+]i transient that may propagate towards the soma. The activation of these Ca2+ channels at a low-voltage threshold is likely to influence the way in which dendritic EPSPs contribute to the electrical activity of the neuron. PMID- 8197210 TI - Constructive advice for a poorly understood problem: treatment and management of premenstrual syndrome. AB - While women are increasingly seeking therapeutic help for premenstrual syndrome, lack of understanding of its aetiology means treatment focuses more on the symptoms than the underlying cause. A sympathetic approach based on counselling, practical advice and reassurance, however, can help many women to tackle the symptoms before they become more severe. PMID- 8197211 TI - Are you prepared to be their advocate? Issues in patient advocacy. AB - Patient advocacy is fraught with legal, ethical and professional difficulties. This article describes some of the advocacy issues that are likely to be encountered in a palliative care setting, and shows how decision-making must reflect legal and ethical considerations. PMID- 8197212 TI - The cognitive model and treatment of depression. AB - 1. Research indicates that depression is best treated using a combination of drugs and psychological interventions. 2. The Beck psychological model of depression has led to a specific treatment formulation. 3. Beck sees the dysfunctional cognitions which arise in how person sees him- or herself, the world, the future, as contributory to the illness. 4. Research using both qualitative and quantitative analysis has shown cognitive therapy to be an effective form of treatment for depression. PMID- 8197213 TI - No more cause for neglect. Introducing a nutritional assessment tool and action plan. AB - Research points to unacceptably high rates of malnutrition in hospital patients. An assessment tool and action plan were devised, based on the Waterlow system, to help nurses quickly identify and take steps to overcome this problem in a structured way. PMID- 8197214 TI - Preventing infection during i.v. therapy. AB - 1. Intravenous devices are susceptible to infectious complications because bacteria can migrate into the bloodstream from the skin along the cannula, from the hub or sideport of the cannula and from contaminated IV fluid. 2. Insertion of an IV cannula should be considered a minor surgical procedure and carried out with a high standard of asepsis. 3. There is conflicting evidence about the best type of dressing to cover the insertion site. 4. The relevant research on preventing infection associated with IV lines is discussed and related to practice. PMID- 8197215 TI - Is this the best intervention? A case study approach to decision-making. AB - It can be difficult to challenge the decision of a doctor, but if nurses believe that a decision is wrong, it is their duty to do so. This article shows how a structured decision-making process can not only aid nurses to do this, but can also aid them in all areas of clinical practice. PMID- 8197216 TI - More than an information service? Should genetic services offer clients counselling? AB - As knowledge and techniques develop in predicting genetic conditions, more genetic services are being established. This article explores whether such services should offer counselling to their clients. PMID- 8197217 TI - An emphasis on practical management. Discharge planning in stoma care. AB - As stoma patients are being discharged from hospital earlier, nurses have less time to teach them how to manage their stoma. It is essential, therefore, that they focus on the practical implications of stoma care to reduce stress in the immediate post-discharge period. PMID- 8197218 TI - Finding the formula to enhance care. Guidelines for the use of complementary therapies in nursing practice. AB - Complementary therapies, particularly aromatherapy and therapeutic massage, can benefit many people by providing comfort and relaxation. It is important, however, that nurses administering these therapies are adequately trained in techniques and the selection of appropriate oils. PMID- 8197219 TI - A hazard we can no longer ignore. Effects of excessive noise on wellbeing. AB - Exposure to excessive noise can lead to hearing loss and contribute to other illnesses and accidents. Recent legislation requires that employers ensure employees are protected from high noise levels in the workplace. It is important that nurses are aware of these requirements, and see that they are fulfilled. PMID- 8197220 TI - Endpiece. The non-trauma of a stroke. PMID- 8197221 TI - [Epibatidine]. PMID- 8197222 TI - [MPTP--neurotoxin and model substance in Parkinson research]. PMID- 8197223 TI - [The snakes of Germany. Distribution, characteristics and poisonousness]. PMID- 8197224 TI - [Classical pharmacognosy, a science with a future?]. PMID- 8197225 TI - [Antimalarial 10 H-indolo(3,2-b)quinolin-11-yl-amines. 1. Phenol-Mannich-bases of the amodiaquine and cycloquine type]. AB - The 11-chloro-quinoline derivatives 3 react with 4-aminophenol and the mono- and bis-phenol-Mannich-bases 6 to yield the 10H-indolo[3,2-b]quinoline-11-yl-amines 4 and 7. The amodiaquine analogue 7a as the best of all compounds shows a comparable activity with choroquine and inhibits a multiresistant Plasmodium falciparum strain at the same concentration. Compound 7e from the cycloquine-type was selected for an in vivo antitumor screening programme. PMID- 8197226 TI - Bioavailability of glycyrrhizin and licorice extract in rat and human plasma as detected by a HPLC method. AB - The pharmacokinetic behaviour of glycyrrhizin (1) was investigated in order to evaluate the difference in bioavailability after oral administration of licorice extract (LE) or glycyrrhizin (1) to rats and humans. For this study, two reliable HPLC methods were developed for the dosage of the levels of 1 and of its metabolite, the glycyrrhetic acid (2) in plasma samples. The determinations were carried out by HPLC on a reversed phase column with UV detector (251 nm), after a careful extraction step of 1 and 2 from the biological matrix. These methods afford good accuracy and satisfactory precision and they allow the determination of both compounds at levels as low as 200 ng/ml. The analytical results improved the knowledge of 1 pharmacokinetics, showing a significantly reduced bioavailability, when administered as LE compared to 1 when administered as such. PMID- 8197228 TI - Antitumoral activity of patulin and patulin-cysteine adducts. AB - A comparison between the cytotoxicity and the anti-tumoral activity of patulin and patulin-cysteine adducts has been conducted. In vitro assays using L 1210 and P 388 cells showed that patulin-cysteine adducts had less cytotoxic activity than patulin (IC50 was 4 fold of IC50 patulin). In vivo, cysteine not only reduced the toxicity of patulin but also reduced its antitumoral activity against L 1210 and P 388 mouse leukemias (respectively of 25.7% and 46.6% with 3 mg.kg-1.d-1). By addition on patulin at the 4 or 7 position, cysteine might interfere with the lactone function and the -CH2- in in position 6 which are responsible for the antitumoral activity. PMID- 8197227 TI - MAOI activity of thiosemicarbazides and related 2-thiazolylhydrazines. AB - The preparation is described of hydrazides I, thiosemicarbazides II, III, IV and hydrazinothiazoles VIII, which can be considered as "precursors" or "open models" for the synthesized benzoyl-, benzilidene- and benzyl-hydrazinothiazoles V, VI and VII, analogous to 4-methyl and 4-phenyl substituted derivatives A, B and C, described and tested for their MAOI activity in a previous paper. Biochemical assay on the new prepared compounds allowed us to better clarify the structure activity relationship also of compounds A, B and C of the precedent note. Moreover, on a group of derivatives, which showed a higher activity, a further test was performed to observe the possible correlation between MAOI activity and both their lipophilicity and ability in interacting with liposome bilayers, taken as a model of cell membrane. PMID- 8197229 TI - Antimicrobial and antitumoral activities of 6-allyl-5,6-dihydro-5-hydroxypyran-2 one, a lactone produced by a new Drechslera species. AB - Antifungal, antibacterial and antitumoral properties of 6-allyl-5,6-dihydro-5 hydroxypyran-2-one were researched. This compound was isolated from culture medium of a new Drechslera species from the area of the Dead Sea. The product exhibited a large activity spectrum against microorganisms, with interesting IC 50 values close to those obtained with reference compounds (kanamycin and ketoconazole). Antitumoral potentiality was 10 to 58 times less important than with doxorubicin, however IC 50 obtained were below 4 micrograms/ml, which is the threshold value proposed by National Cancer Institute for preliminary screening of active molecules. PMID- 8197230 TI - Metabolites of Pseudevernia furfuracea (L.) Zopf. and their inhibition potential of proteolytic enzymes. AB - Atranorin (1), physodic acid (2), oxyphysodic acid (3) and virensic (4) acid were identified in P. furfuracea, a lichen species collected in West Tatra. According to HPLC analysis contents of these metabolites in dried material was 0.11-0.19% (1), 1.46-3.78% (2), 1.69 to 3.44% (3), 1.14-1.46% (4). Atranorin was the strongest inhibitor of trypsin as well as of the porcine pancreatic elastase. PMID- 8197231 TI - Study of local anaesthetics. Part 121: Correlation between log k', C, RF, RM and local anesthesia for perhydroazepinyl ethyl esters of 2-, 3- and 4 alkoxyphenylcarbamic acids. PMID- 8197232 TI - [Micromethod for determination of amrinone and acetylamrinone in plasma and urine with HPLC]. PMID- 8197233 TI - [The effect of lecithin type on the absorption of vitamins A and E from liposomes in the skin]. PMID- 8197234 TI - In vitro antitumor activity of fused 2-carboxaldehyde N,N-dimethylhydrazone-3 methylfuran derivatives. PMID- 8197235 TI - Adenosine deaminase activity in gastric mucosa of pernicious anemia patients. Effect of treatment with cyanocobalamin (vitamin B12). PMID- 8197236 TI - Antimicrobial effects of some hydroxycoumarins and secoiridoids from Fraxinus ornus bark. PMID- 8197237 TI - Proliferation of schools. PMID- 8197238 TI - Health status of individuals entering a cardiac rehabilitation program as measured by the medical outcomes study 36-item short-form survey (SF-36). AB - BACKGROUND AND PURPOSE: The goal of health care for individuals with chronic disease is the improvement of function and well-being. Although the individual's perception of his or her quality of life may be the best indicator of achievement of this goal, measurement of self-perceived quality of life, or health status, is not a routine component of evaluation. The purposes of this article are to describe the health status of individuals upon entry into a cardiac rehabilitation program and to demonstrate the use of a comprehensive, generic health status measure in this group. SUBJECTS: The subjects of this study were 789 men and women enrolled in one of 13 cardiac rehabilitation programs in the state of Massachusetts. METHODS: As part of a large database, subjects completed a 36-item generic questionnaire, Short Form 36 (SF-36), that examines eight health concepts. Scores range from 0% to 100%; a higher score is consistent with better health status. Results. Mean uncontrolled scores ranged from 26.6 to 70.8. Mean scores adjusted for sex, age, and education ranged from 27.1 to 70.9. In light of previously published data using a similar 20-item scale, our results show that cardiac disease is associated with reductions in health-related quality of life. CONCLUSION AND DISCUSSION: Health status measurement provides information that can supplement the usual measures of impairment in patients with cardiovascular disease. The findings of this study contribute to the understanding of health status of individuals who enroll in cardiac rehabilitation programs. The health status instrument used in this study has potential as a useful, practical measurement tool for use in the clinical setting. PMID- 8197239 TI - Assessing change over time in patients with low back pain. AB - BACKGROUND AND PURPOSE: This study compared the ability of the Roland-Morris (RM), Oswestry (OSW), and Jan van Breemen Institute (JVB) pain and function questionnaires to detect change over time. SUBJECTS: The sample consisted of 88 patients with mechanical low back pain who were referred by physicians to the outpatient physical therapy department of a teaching hospital. METHODS: Questionnaires were completed by the subjects at their initial visit and 4 to 6 weeks later. Clinically important change was estimated by having the subject and the clinician independently complete two rating scales. Sensitivity to change was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: The ROC curve areas for the RM (0.79), OSW (0.78), and JVB pain (0.79) questionnaires were significantly greater than for the JVB function questionnaire (0.66). Blank and multiple responses per item were present on approximately 20% of the OSW questionnaires and 14% of the JVB questionnaires. Words rather than checks were evident on 3% of the RM questionnaires. CONCLUSION AND DISCUSSION: Based on the latter finding, we believe the RM questionnaire may be the preferred instrument for assessing change over time in patients with low back pain. PMID- 8197240 TI - Efficacy of electromyographic biofeedback compared with conventional physical therapy for upper-extremity function in patients following stroke: a research overview and meta-analysis. AB - BACKGROUND AND PURPOSE: The purpose of this study was to examine the efficacy of electromyographic biofeedback compared with conventional physical therapy for improving upper-extremity function in patients following a stroke. SUBJECTS AND METHODS: A literature search was done for the years 1976 to 1992. The selection criteria included single-blinded randomized control trials. Study quality was assessed for nine criteria. For functional (disability index or stage of recovery) and impairment outcomes, meta-analyses were performed on odds ratios for improvement versus no improvement. Mann-Whitney U-Test probability values were combined across studies. RESULTS: Six studies were selected, and outcome data were obtained for five studies. The common odds ratio was 2.2 for function and 1.1 for impairments in favor of biofeedback. The estimate of the number needed to treat to prevent a nonresponder was 11 for function and 22 for impairments. None of the meta-analyses were statistically significant. CONCLUSIONS AND DISCUSSION: The results do not conclusively indicate superiority of either form of therapy. Although there is a chance of Type II error, the estimated size of the effect is small. Given this estimate of little or no difference, therapists need to consider cost, ease of application, and patient preference when selecting these therapies. PMID- 8197241 TI - A manual therapy approach to evaluation and treatment of a patient with a chronic lumbar nerve root irritation. AB - The purpose of this case report is to familiarize the reader with the basic principles of the approach to manual therapy evaluation and treatment pioneered by Maitland, an Australian physical therapist. This approach involves a complete subjective examination to determine the severity, irritability, nature, and stage of the patient's complaints. In this way, the therapist may reach conclusions as to the amount and vigor of the physical examination and proceed with treatment in an analytical manner. Methodical reassessment is used to justify treatment progression. Comprehensive treatment and the rationale for this approach are discussed. Though most physical therapists are familiar with the straight-leg raising test as a means of assessing low back pain and chronic lumbar nerve root irritation, they are often not familiar with other tests that examine neural tissues, such as the slump test. The proposed anatomical and biomechanical bases for these tests are discussed. The patient in this case study was a 50-year-old man with a physician's diagnosis of a chronic lumbar nerve root irritation. The patient was evaluated and treated in eight visits using techniques designed to evaluate neural tissues. Reassessment indicated significant symptom reduction, and the treatment was modified accordingly. Patient management, including home exercises, is discussed. PMID- 8197242 TI - Immediate effects of the toe spreader on the tonic toe flexion reflex. AB - BACKGROUND AND PURPOSE: The purpose of the study was to determine whether the use of a toe spreader to inhibit the tonic toe flexion reflex (TTFR) immediately alters temporal-distance gait characteristics, plantar surface contact, or muscle activity in the limb exhibiting the TTFR of subjects with hemiparesis secondary to supraspinal lesion. SUBJECTS: Eighteen adults with hemiparesis secondary to supraspinal lesions served as subjects for the standing portion of the study. Sixteen of the subjects participated in the gait portion of the study. METHODS: The study was a randomized, within-subject, between-conditions comparison consisting of standing and gait phases, with four conditions for each phase (shoe off, toe spreader off/on, shoe on, toe spreader off/on). Measures performed were ink footprint gait analysis and integrated electromyography from the limb exhibiting the TTFR. RESULTS: Presence of the TTFR was reduced significantly with the use of the toe spreader. Velocity and cadence were increased significantly by use of the toe spreader. CONCLUSION AND DISCUSSION: The toe spreader may be a useful treatment option for improving gait. The clinical significance of these findings, however, will depend on the functional context of toe-spreader use. PMID- 8197243 TI - Physical therapists' perceptions of the roles of the physical therapist assistant. AB - BACKGROUND AND PURPOSE: This longitudinal study investigated physical therapists' perceptions of the roles of physical therapist assistants (PTAs). METHODS AND SUBJECTS: In 1986, a questionnaire describing 79 physical therapy activities was distributed to a random sample (n = 400) of physical therapists derived from the American Physical Therapy Association (APTA) membership. In 1992, a similar questionnaire was distributed to a representative sample (n = 400) of physical therapists derived from the APTA membership. Response rates were 53% and 55% in 1986 and 1992, respectively. Respondents indicated whether each activity was included in the documentation describing PTA roles. RESULTS: Results revealed considerable agreement between therapists' perceptions of PTA roles and those outlined by PTA practice guidelines, and these perceptions changed little over time. Discriminant analyses suggested that therapists' perceptions of PTA roles were, in general, not predicted by supervisory experience with PTAs, therapist experience, or content of entry-level professional education curricula. CONCLUSION AND DISCUSSION: Generally, therapists' perceptions of PTA roles are consistent with published practice guidelines. Therapists' perceptions on selected activities, however, were incongruent with PTA practice guidelines, suggesting the potential for inefficient or inappropriate utilization of the PTA in the delivery of selected services. PMID- 8197245 TI - Sixty-seventh president of APS. Brian R. Duling. PMID- 8197244 TI - The effect of a comprehensive, intensive inpatient treatment program on lung function and exercise capacity in patients with cystic fibrosis. AB - BACKGROUND AND PURPOSE: The purpose of this investigation was to measure the effects of a 10- to 14-day comprehensive, intensive hospital treatment program on peak exercise capacity, endurance capacity, respiratory function, weight change, and maximum inspiratory and expiratory mouth pressures in patients with cystic fibrosis with a pulmonary exacerbation. SUBJECTS: Fourteen young adults with cystic fibrosis admitted to a hospital for an exacerbation of their pulmonary disease were studied. METHODS: Subjects performed pulmonary function tests, inspiratory and expiratory mouth pressure tests, and stationary bicycle exercise tests at admission and discharge. Comprehensive therapy provided during the hospital admission consisted of intravenous antibiotics, physical therapy, high calorie diet, and daily medical review. RESULTS: The patients showed improvements in forced expiratory volume in 1 second (46%-55% of predicted values) and forced vital capacity (62%-68% of predicted values). Maximum inspiratory and expiratory mouth pressures also improved (118%-131% and 78%-92% of predicted values, respectively). There was a mean weight gain of 2 kg. Maximum work capacity on a bicycle ergometer improved from a mean of 45% to 52% of predicted values. The most impressive result was the marked increase in exercise endurance time from a mean of 9.5 minutes on admission to 16.6 minutes at discharge. CONCLUSION AND DISCUSSION: This study indicates that young adults with cystic fibrosis and an exacerbation of their pulmonary disease obtain measurable benefits from a comprehensive, intensive treatment program, particularly improvement in their capacity for endurance exercise. PMID- 8197246 TI - Accreditation, curricular change, and other disturbances of the steady state. PMID- 8197247 TI - APS gives views on NIH guide. PMID- 8197248 TI - Dietary guidance and nutrient requirements of the elderly. AB - Basic practical advice about healthy food choices is reviewed via the Dietary Guidelines for Americans, the Food Guide Pyramid, and Daily Values on Food Labels. Special considerations for their use with the healthy elderly are included. Nutrient requirements of the elderly are presented for the oldest RDA age category, "51+ years and older" as is newer research on altered nutrient needs that accompany aging. The Nutrition Counseling Checklist helps determine when referral for in-depth diet therapy is needed. PMID- 8197249 TI - Dementia, depression, and nutritional status. AB - Dementia, depression, and Parkinson's disease are in themselves challenging problems in old age. Recognition and diagnosis are often suboptimal. In dementia, many contributing factors must be considered, including nutrition, but in all these conditions the effects of the cognitive, attitudinal, and motor changes can produce permanent and severe nutritional compromise. Yet many simple steps can be taken to prevent poor nutrition in these diseases, and the primary care practitioner is central to this process of recognition and intervention. PMID- 8197250 TI - Oral health and nutrition. AB - The relationships between oral health conditions, dietary practices and nutritional status, and general health status in the older American are complex, with many interrelating factors. Just as inadequate nutrition can affect oral health, poor oral health status affects food choices and, thus, nutritional status. It is clearly essential that the primary care practitioner and/or screening health professionals always include an evaluation of oral status in assessment of an elderly person. Effective care for the elderly dental patient requires knowledge about the disease of aging and the impact of those diseases on oral health and nutrition, pharmacology and drug interactions and their impact on oral health status, the biology of aging including sensory changes, the relationship of general medicine and systemic diseases, and psychology and sociology. The attitudes of empathy and understanding, caring and compassion, respect and a positive attitude toward the older patient, and flexibility in treatment planning are also critical elements. The interdisciplinary team of physicians, nurses, nutrition professionals, dentists, and social service professionals must all work together to ensure that good oral health status and adequate nutrition are maintained in older Americans. Recognizing and treating oral health and nutrition problems are important in improving the health and quality of life for the elderly population. Research that can provide more answers to health care problems in this growing group; educating professionals with respect to the relationships between oral health and nutrition; and public policy changes with regard to provision and funding of nutrition services, especially when provided by registered and/or licensed nutrition professionals, contribute to improving the health and quality of life for elders. PMID- 8197251 TI - Medications and nutrition in the elderly. AB - Single drug and drug combinations taken by elderly individuals may impose nutritional risk. Nutritional risk induced by drug intake include anorexia, excessive increase in appetite, drug-induced nutritional deficiencies, and toxic reactions. Drug side effects, such as postural hypotension, may interfere with food shopping or cooking ability. Prescribed diets may also impose a risk of drug induced side effects or diminished drug efficacy. Unwanted outcomes of drug-food and drug-nutrient interactions can be minimized by instructing elderly men and women and their caregivers to avoid timing errors in drug-taking behavior and toxic reactions due to food incompatibility. In addition, drug-induced nutritional deficiencies can be avoided by advising drug-taking elderly on the appropriate levels of nutrient intake. PMID- 8197252 TI - Nutrition support, supplementation, and replacement. AB - Nutrition support in acute, chronic, or home care settings can be implemented successfully by the well-informed primary care physician, who often is the first to identify poor nutritional health in his or her patients. Using established protocols for the identification or of risk factors and indicators of malnutrition, specific alerts to the need for nutrition support are presented. The logical approach to nutrition support interventions through four stages representing the gradual increase in complexity and cost, paralleling the progressive inability to use regular foods and the gastrointestinal tract are discussed. Specific, practical measures that can be recommended and implemented by the primary care physician managing the older person are presented. The ethical, legal, and home health aspects of nutrition support in the care of the older American by the primary care physician are also reviewed. PMID- 8197253 TI - Specific dietary interventions. Diabetes, osteoporosis, renal disease. AB - A dietary treatment plan that considers both quality-of-care and quality-of-life issues is most beneficial for elderly patients. Diabetes can be successfully managed in most elderly patients with a liberalized diet that is low in simple sugars and includes variety and moderation in food choices. Although dietary management in osteoporosis may be most compelling in its preventive capacity, clinicians treating elderly patients with osteoporosis are well advised to consider supplementation of the diet with calcium and vitamin D in amounts equal to the RDAs if patients are unable to consume adequate calcium and vitamin D and if exposure to sunlight is minimal. Encouraging calcium intake, moderate exercise, maintenance of desirable body weight, and avoidance of laxative and antacid abuse with patients throughout the life cycle is appropriate preventive advice. The elderly renal failure patient may benefit from dietary modification of protein, potassium, sodium, fluid, vitamins, and minerals when complications associated with these nutrients are present. Because clinicians treat significant numbers of elderly diabetic, osteoporotic, and renal failure patients, and because many skilled nursing facilities are developing specialty and rehabilitation units for such high-acuity level patients, the clinician is well advised to know how to maximize quality of care and quality of life for these patients through appropriate dietary intervention. PMID- 8197254 TI - Risk factors for poor nutritional status. AB - Nutrition risk can be assessed in elderly populations by evaluating such factors as food intake, income, functional status, socialization, acute and chronic illness, and use of medications. Nutrition screening must become an integral component of the health care services provided for all older Americans. Nutrition screening and early intervention are primary steps in the development of a system of health care that is affordable and accessible to all. PMID- 8197255 TI - Intensity of treatment in malnutrition. The ethical considerations. AB - Decisions about initiation and withdrawal of life-sustaining artificial nutrition and hydration are complex and sometimes are agonizing to make. Artificial feeding is considered by most medical ethicists to be a medical intervention about which decisions should be made based on the benefits, risks, and burdens of the treatment. State law varies, particularly with regard to the inclusion of artificial feeding in advance directives and in laws about its discontinuance. Conditions in which it is common for patients or families to consider refusal of artificial feeding include terminal cancer, advanced dementia, and persistent vegetative state. Alternative approaches to nutrition, such as offering favorite foods or treating underlying depression, may obviate the need for tube feeding. Competent patients may refuse any medical treatment, including life-sustaining treatment. An appropriate proxy decision maker may also refuse treatment on behalf of a mentally incapacitated patient. PMID- 8197256 TI - The signs and symptoms of poor nutritional status. AB - Many signs and symptoms suggest poor nutritional status, and some have been categorized by consensus of the Nutrition Screening Initiative as "major indicators"; this term implies that, if certain standards of change from the norm in that parameter have occurred, poor nutritional status as a cause must be considered and appropriate steps taken to correct such poor nutritional status if confirmed. Virtually all of the signs and symptoms of poor nutritional status are nonspecific and may be caused or exacerbated by other medical conditions. However, by categorizing them as major or minor indicators and summarizing them, the hope is that practicing health professionals will more frequently note these commonly observed changes, appreciate their nutritional significance, and implement nutritional interventions to correct the problems thus preventing the increased morbidity and mortality known to occur in the malnourished older individual. PMID- 8197257 TI - Screening for nutritional status in the elderly. AB - A comprehensive assessment of nutritional status is a critically important component of any patient evaluation. Based upon clinical information, anthropometric data, and a small number of laboratory investigations, an accurate appraisal of nutritional status should be possible and an appropriate intervention plan can be developed. The actual approach depends on the particular problem discovered. These are discussed in detail elsewhere in this issue. PMID- 8197258 TI - Educating the family and the patient about nutrition. AB - Patients and their families deserve sound nutrition advice from primary care practitioners. By using a systematic, community-based approach, the health care provider can integrate nutrition teaching into routine health care. Practitioners should be positive and enthusiastic, should keep nutrition messages simple and food specific, and should recognize that patient lifestyle behaviors will change incrementally and slowly. PMID- 8197259 TI - Social services to assist nutrition. AB - Social services to assist in improving nutritional status in older adults are reviewed. The social service interventions are placed in three broad categories of risk for older people to include poverty, social isolation, and dependency/disability. Each social service is identified and described to include eligibility and local resources. A social services intervention contact guide is provided as well as a state-by-stage aging services and resources directory. PMID- 8197260 TI - [Schizophrenia as a metaphor]. PMID- 8197261 TI - [Suicide prevention in inpatient psychiatric treatment. I: Review of the literature]. AB - Reviewing the literature factors of suicide-prevention on Psychiatric wards are specified. Suicide crisis is interpreted as narcissistic crisis. On the background of new findings of the American baby-watchers considerations were made on the development of the self and pathologic states of self with respect to suicidal patients. PMID- 8197262 TI - [Suicide prevention in inpatient psychiatric treatment. II: Intraindividual and interindividual suicide prevention]. AB - After describing decisive factors of suicide prevention on Psychiatric wards criterias are developed to diagnose the self-states of acute suicidal psychiatric patients. Guidelines for an intraindividual and interindividual suicide prevention are presented. PMID- 8197263 TI - [Attitude of medical students to treatment with psychotropic drugs. 1: Comparison between medical students and the general population]. AB - The attitudes of medical students towards psychotropic drugs are compared with those of the general public. Students strike a more positive balance between the costs and benefits of this treatment method. Whereas there are no marked differences as concerns desirable effects both groups differ considerably in the assessment of the limitations and risk of undesirable side-effects with students being less sceptical in this respect. Also with regard to other attitudinal domains student's judgement is more favourable. However, this does not mean that there is not a remarkably large group which articulates reservations against the use of psychotropic drugs. Whereas the majority of the lay public considers psychotherapy in general as superior to psychopharmacotherapy most students tend to differentiate between the various forms of psychiatric disorder. PMID- 8197264 TI - [Attitude of medical students to treatment with psychotropic drugs. 2: Change in attitude in the course of medical education]. AB - Advanced medical students' attitude to psychotropic drugs is more positive than the lay public's view on that subject (see part I). The question arises if this is a result of the psychiatric and psychopharmacological knowledge students have acquired during their medical education or an effect of selection by which students already have a more positive opinion of psychotropic drugs before the commencement of their medical education. Our survey in three differently advanced groups of medical students (n = 323) was carried out with a questionnaire. In contrast to their scepticism concerning psychopharmacological treatment students in the beginning of their medical education estimate others than psychotropic drugs ly than the lay public. This may be explained by a beginning identification with the model of a quickly and effectively treating doctor. In the course of medical and especially psychiatric and psychopharmacological education, there is a tendency to a more differentiated and positive view on the effects of psychotropic drugs although the generally critical attitude persists. PMID- 8197265 TI - [Schizophrenia: subjective illness theories--an explorative study. 1: Patients]. AB - The growing acceptance of Zubin's vulnerability-stressor-model in research and clinical practice stresses the importance of schizophrenic patients individual coping strategies. Coping strategies are influenced not only by individual cognitions concerning the actual illness but also by opinions of key-persons within the social network of the patient. Research on the acquisition of patients subjective view of the schizophrenic illness has to integrate both the individual psychological resources as well as the social context variables. The present paper reports about in depth open interviews with six patients and their key relatives. The results were derived from a structural analysis of the tape recorded and transcribed interviews. Patients showed a broad variety of etiological explanations of their illness and expressed a need for more comprehensive information (part 1). Parents stated a more pessimistic prognosis of the course of illness than patients. Both patients and parents complained about the lack of mutual communication about the illness and its symptoms (part 2). Implications of these results concerning psychoeducational programs for patients and families as well are discussed. PMID- 8197266 TI - [A separate special consultation for relatives]. AB - Relatives of mental ill have their own problems. This paper resumes first experiences with a special offer for relatives. The adviser must not be involved in the therapy with the sick member of the family. PMID- 8197267 TI - [Cerebral convulsion after 100 mg clozapine]. PMID- 8197268 TI - Abnormal plasma levels of serine, methionine, and taurine in transient acute polymorphic psychosis. AB - The present study explored the usefulness of plasma amino acid concentrations in discriminating a subgroup of patients with transient acute polymorphic psychoses characterized by psychosensory symptoms (APP+ patients). Levels of amino acids in the plasma of APP+ patients were compared with levels in psychiatric patients with other types of psychotic symptomatology and a healthy control group. Both the APP+ patients and patients with bipolar affective disorder had significantly lower plasma concentrations of serine compared with concentrations in the other groups studied. Since the plasma concentrations of taurine and methionine were also different in the APP+ patients, the ratio of taurine to the product of serine and methionine (the TSM ratio) was used in an attempt to increase the sensitivity in discriminating these patients. The TSM ratio in the APP+ patients was significantly higher than those in the other groups studied, except for the patients with bipolar affective disorder. It appears that the determination of serine and the TSM ratio in the plasma of psychotic patients may be a useful diagnostic validator in a group of patients with acute polymorphic psychoses. PMID- 8197269 TI - Standardized mood induction with happy and sad facial expressions. AB - The feasibility of applying ecologically valid and socially relevant emotional stimuli in a standardized fashion to obtain reliable mood changes in healthy subjects was examined. The stimuli consisted of happy and sad facial expressions varying in intensity. Two mood-induction procedures (happy and sad, each consisting of 40 slides) were administered to 24 young healthy subjects, who were instructed to look at each slide (self-paced) and try to feel the happy or sad mood expressed by the person in the picture. On an emotional self-rating scale, subjects rated themselves as relatively happier during the happy mood-induction condition and as relatively sadder during the sad mood-induction condition. Conversely, they reported that they were less happy during the sad mood-induction condition and less sad during the happy mood-induction condition. The effects were generalized to positive and negative affect as measured by the Positive and Negative Affect Scale. The intraindividual variability in the effect was very small. In a retest study after 1 month, the mood-induction effects showed good stability over time. The results encourage the use of this mood-induction procedure as a neurobehavioral probe in physiologic neuroimaging studies for investigating the neural substrates of emotional experience. PMID- 8197270 TI - Stressful life events, social rhythms, and depressive symptoms among the elderly: an examination of hypothesized causal linkages. AB - This study sought to determine possible causal linkages among stressful life events, social rhythms, and levels of depressive symptomatology for 81 elderly subjects (51 recently widowed, 30 healthy controls). We examined the associations among stressful life events (i.e., bereavement status at baseline or a severely threatening event occurring between baseline and followup), social rhythm stability, and the level of depressive symptoms. Results indicated that while stressful life events were not associated with significant changes in social rhythm stability, social rhythm stability was a significant negative correlate of both baseline and followup levels of depressive symptomatology; that is, lower levels of social rhythm stability at baseline were associated with high levels of depressive symptoms at baseline (rho = -0.33, n = 81, p < 0.001) and at followup (rho = -0.23, n = 81, p < 0.05). Bereavement was also a significant positive correlate of depressive symptomatology both at baseline (rho = 0.79, n = 81), p < 0.0001) and at followup (rho = 0.55, n = 81, p < 0.0001). It is likely that future research will benefit from social rhythm assessment obtained temporally closer to major life events and from the use of structured interviews to ascertain the presence of syndromal major depression at followup as well as the inclusion of subjects with a wider range of functional impairments. Nevertheless, these results represent a first step in disentangling possible causal connections among stressful life events, social rhythms, and depressive symptomatology. PMID- 8197271 TI - Psychological and endocrine abnormalities in refugees from East Germany: Part I. Prolonged stress, psychopathology, and hypothalamic-pituitary-thyroid axis activity. AB - The influence of prolonged psychological stress on hormonal secretion was investigated in 84 East Germany refugees suffering from psychiatric disorders within 6 weeks of their arrival in West Berlin shortly before or after the fall of the Berlin Wall. Before leaving the German Democratic Republic, these patients had already experienced prolonged stress, which continued after migration. In most cases, the diagnosis was anxious-depressive syndrome with vegetative complaints and symptoms of increased arousal. Their formal DSM-III-R diagnoses (American Psychiatric Association, 1987) included adjustment disorders, depressive disorders, and anxiety disorders (the latter including posttraumatic stress disorder). Serum levels of thyroid stimulating hormone (TSH) and thyroid hormones (thyroxine, free thyroxine, triiodothyronine, and reverse triiodothyronine) were measured and compared with those of 20 healthy control subjects. TSH and all thyroid hormone concentrations were significantly reduced in the patient group. Fifty-two of the patients (62%) were in the hypothyroid range but did not show any clinical signs of hypothyroidism. These disturbances in hormonal secretion were not correlated to any psychiatric diagnosis or to the severity of acute or chronic stress. The marked abnormalities in the hypothalamic pituitary-thyroid axis seen in these refugees differ from those reported in depression and would seem to reflect severe chronic stress rather than specific psychiatric disorders. The underlying neurochemical mechanisms remain to be investigated. PMID- 8197272 TI - Psychological and endocrine abnormalities in refugees from East Germany: Part II. Serum levels of cortisol, prolactin, luteinizing hormone, follicle stimulating hormone, and testosterone. AB - We investigated afternoon serum levels of cortisol, prolactin, luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone in a group of 84 refugees who had fled from East to West Germany and suffered from psychiatric disorders within 6 weeks of their arrival in West Berlin. The mean hormone levels were compared with those of healthy control subjects. Cortisol levels were lower and LH levels were higher in the patients than in the control subjects, but only at trend levels of significance. No differences were found between the prolactin, FSH, or testosterone concentrations of the two groups. The patients with major depressive disorder (MDD) had a significantly higher mean cortisol level than the mean levels in the subgroups in whom posttraumatic stress disorder, dysthymia, and adjustment disorder were diagnosed. It can be concluded that the hypothalamic pituitary-adrenal axis may "adapt" during severe long-term psychological stress and that long-term stress may be only one of the neurochemical mechanisms underlying the hypercortisolemia in patients with MDD. PMID- 8197273 TI - Lithium maintenance therapy for bipolar I patients: possible refractoriness to reinstitution after discontinuation. PMID- 8197274 TI - Behavioral change with environmental change. AB - The influence of sheltered workshop and community employment on inappropriate behaviors of six people with developmental disabilities was examined. During the first 3 months of community employment the mean decrease in targeted behaviors was 94%. PMID- 8197275 TI - Information-processing styles of paranormal healers. AB - 49 paranormal healers working by laying-on-of-hands (direct healing) and distance healing were compared with 56 nursing staff and a control group of 73 on the information-processing styles of field-dependence and reflexivity-impulsivity. Apparently paranormal healers scored as more field-dependent than the other groups which is consistent with observations of paranormal healers when working. No differences appeared among groups on reflexivity-impulsivity. PMID- 8197276 TI - Detection of faking on role-play tests of assertiveness. AB - Faking and demand characteristics can represent significant threats to the validity of role-play tests of social competence. The present study examined whether faking could be detected via the global judgments of experienced and inexperienced assessors. 26 undergraduates low in assertiveness were induced to fake their performances on the Idiographic Role-play Test via instructions and information. Experienced judges successfully differentiated faking subjects from highly assertive subjects (n = 27) who had been provided with information and nonfaking instructions (98% accuracy). Inexperienced assessors correctly classified 79% of the subjects. Within the discussed limitations of this study, it appears that it is possible to detect faking on role-play tests of assertiveness. PMID- 8197277 TI - Effect of "mood that day" on pharmacists' job and career satisfaction. AB - We speculated that mood would affect responses to global measures of job and career satisfaction. We randomly selected 692 pharmacists from the Iowa Board of Pharmacy Examiners' mailing list. After two follow-up mailings, 389 questionnaires were received for a usable rate of 56.9%. "Good day" pharmacists were more satisfied with their jobs and careers than "typical day" pharmacists, supporting the contention that global satisfaction indicators reflect affective satisfaction. PMID- 8197278 TI - Student-Life Stress Inventory: identification of and reactions to stressors. AB - The purposes of the study were to analyze responses to a stress inventory and assess significance of differences by gender and stress groups on the stressors and reactions to them. The subjects were 290 volunteers who responded to the Student-life Stress Inventory. Analyses showed the inventory is reliable and valid. Differences were noted by gender and amount of stress for types of stressors students experienced and reactions to them. PMID- 8197279 TI - Kindergarten predictors of first-grade reading achievement: a regular classroom sample. AB - Routinely collected measures for 38 children in the kindergarten program in a middle-class school in a small midwestern city were analyzed as predictors of first-grade reading achievement on the Iowa Tests of Basic Skills and of first grade performance on the Cognitive Abilities Test. Correlations among all variables are given. Stepwise multiple regression analyses predicting the first grade variables showed that consonant-sound-identification was the best predictor of first-grade reading achievement and that the Peabody Picture Vocabulary Test- Revised was the best predictor of cognitive ability. A second multiple regression analysis examined the contribution of each kindergarten variable to first-grade reading and cognitive scores. Analysis indicated that these children entered kindergarten with highly developed early reading skills which facilitated success with systematic reading instruction. PMID- 8197280 TI - Considerations in misdiagnosis of narcissistic personality disorder. AB - The present paper identified some diagnostic considerations which might be responsible for misdiagnoses of narcissistic personality disorder. Although conventional diagnostic criteria, e.g., DSM-III-R, for narcissistic personality disorder have suggested a rather homogeneous set of features including, e.g., inflated grandiosity, excessive omnipotence, overt arrogance, diminished empathic capacities, onanistic behavior, pathological self-centeredness, and propensities toward self-indulgence, many narcissistic conditions are misdiagnosed because the symptoms are less obvious if not altogether camouflaged. Diagnostic miscalculations can often mislead clinicians from focusing on verifiable and essential aspects of the disorder and lead to unnecessary therapeutic detours and eventual failures. Improved recognition of the heterogeneity of such patients might improve diagnostic consistency and eventual therapeutic outcome. PMID- 8197281 TI - Correlations of scores on the Gifted Evaluation Scale with those on WISC-III and Kaufman Brief Intelligence Test for students referred for Gifted Evaluation. AB - 29 students (M age of 8.0 yr.) who were referred for evaluation were administered the Gifted Evaluation Scale, the Kaufman Brief Intelligence Test, and the WISC III. Paired t tests comparing the mean GES Quotient with the K-BIT mean IQ and WISC-III Verbal, Performance, and Full Scale IQs yielded no statistically significant differences (range of IQs = 120.6 to 122.9). While the significant correlation of the GES Quotient and WISC-III Performance IQ was .42, r = -.37 for the GES Quotient and WISC-III Verbal IQ. No significant correlation was found between the GES Quotient and the WISC-III Full Scale or K-BIT IQs. The limitations and implications of the study, with regard to the use of the Gifted Evaluation Scale, are discussed. PMID- 8197282 TI - Underage female DUI offenders: personality characteristics, psychosocial stressors, alcohol and other drug use, and driving-risk. AB - 164 underage female DUI offenders were evaluated on measures of personality, driving-risk, psychosocial stressors, alcohol and other drug use, alcohol abuse, and symptoms of depression. Empirical classification of 10 groups represented five distinct types. 31 youth who were classified as Antisocial exhibited highest rates of alcohol misuse, other drug use, deviant driving behavior, traffic offenses and accidents, and psychosocial stressors. About 56% or 92 appeared to experience impaired functioning serious enough to warrant interventions more intense than educational classes. A measure of driving-risk developed and used in studies of male adults, the Donovan Research Questionnaire, did not appear to differentiate driving-risk among the young women. In contrast to male drivers, who often expressed anger or aggression through driving, most subjects appeared to react to emotion-eliciting stimuli with feelings of low self-worth or dysphoric affect rather than anger. Specialized screening suitable for young female DUI offenders should be considered. PMID- 8197283 TI - Evaluative responses to jokes in informative speech with and without laughter by an audience: a partial replication. PMID- 8197284 TI - Analysis of activities of school counselors. AB - 369 school counselors in Kentucky completed a survey of time allocated to 17 different activities. The allocation of time per activity differed across level of school. Developmental implications of the findings are discussed. PMID- 8197285 TI - A study of the unidimensionality and cumulativeness of the MOS Short-form General Health Survey. AB - The unidimensionality and cumulativeness of the subscales Health Perceptions, Mental Health, Physical Pain, and Social Functioning of the MOS Short-form General Health Survey were investigated using the Mokken Scale Analysis for Polychotomous Items (MSP). From the analyses, two unidimensional, cumulative subscales appeared, Health Perceptions including the item on Social Functioning, and Mental Health. Both subscales met the requirements of the Mokken model, with the first scale being a 'moderately strong' hierarchical scale (H = 0.49, rho = 0.89) and the second a 'weak' hierarchical scale (H = 0.38, rho = 0.85). PMID- 8197286 TI - Sexuality within a Russian geriatric sample: a pilot study. AB - This paper provides preliminary data on sexual functioning within a sample of 19 Russian geriatric respondents who completed selected items from the Starr-Weiner questionnaire assessing areas such as sexual interest and frequency, sexual dysfunction, and sexual attitudes. All 8 men and 9 of the women reported being sexually active. Like American seniors, differences in activity appeared to be moderated by gender and over-all physical health. Sexual dysfunction among these Russians was less than that reported by Stern and Stern in 1979. Also, the Russian seniors reported tolerance toward sexual topics such as homosexuality. Finally, limitations of the present study and research recommendations are mentioned. PMID- 8197287 TI - Comparative study of maternal and paternal disciplinary strategies. AB - Parents (109 mothers, 109 fathers) of 109 middle-class preschool-age children were interviewed separately in individual taperecorded home interviews to assess whether either parent was prone to use assertion of power or inductive reasoning as disciplinary strategies. Fathers reported using more power-assertive disciplining strategies with their preschool-age children than mothers. PMID- 8197288 TI - General and test anxiety, shyness, and grade point average of elementary school children of divorced and nondivorced parents. AB - 116 boys and girls in elementary Grades 4, 5, and 6 were administered the General Anxiety Scale, Test Anxiety Scale, and the Shyness Scale. Their GPAs were obtained from school records as were Normal Curve Equivalents from the Iowa Tests of Basic Skills given the previous school year. Children of divorced parents (n = 31) had lower GPAs than children of nondivorced parents (n = 85). The girls had higher GPAs and general anxiety scores than the boys. The students who scored lower on test anxiety had higher Normal Curve Equivalents. Pearson correlations were significant for scores on Test Anxiety with those on general anxiety (r = .57), GPA (r = -.25), and Normal Curve Equivalents (r = -.26). Normal Curve Equivalents correlated significantly with GPA (r = .66), but shyness did not correlate significantly with any other measure. PMID- 8197289 TI - Personality study of alcohol, heroin, and polydrug abusers in an Arabian Gulf population. AB - Three male groups of heroin, alcohol, and polydrug abusers (n = 120) from an Arabian Gulf population were given Lanyon's Psychological Screening Inventory; their scores were compared with those of a group of 48 nonabusers. Only the polydrug-abusing group of 43 scored significantly higher than the nonabusers on the Alienation and Discomfort subscales. Perhaps only polydrug abuse can be explained in terms of attempts towards self-medication by distressed and inadequate individuals. A drug-accepting-generational age group in contrast to an alcohol-accepting-generational age group was suggested. PMID- 8197290 TI - Acquaintance rape: attributions of victim blame by college students and prison inmates as a function of relationship status of victim and assailant. AB - 53 male college students and 37 male prison inmates completed a questionnaire evaluating an hypothetical rape scenario with a male perpetrator and a female victim. The college students assigned equal blame to the victim regardless of whether the assailant was a stranger or an acquaintance, but the inmates assigned more blame to the victim when the assailant was a stranger than an acquaintance. The results may be interpreted as showing a greater awareness of date or acquaintance rape among the college population than among the prison population. PMID- 8197291 TI - Concurrent validity of the Culture-free Self-esteem Inventory and physical health in college students. AB - 55 college students received the Culture-free Self-esteem Inventory and a 13-item measure of physical health; significant Pearson correlations (generally in the .40s) were found on all but one subscale of the self-concept measure and the health measure. The results are in line with research using other measures of self-esteem and physical health and suggest that the self-esteem inventory may be useful as a research measure. PMID- 8197292 TI - Alexithymia, affect recognition, and the five-factor model of personality in normal subjects. AB - A total of 62 staff members from a general hospital participated in a study about alexithymia and the five-factor model of personality, measured by the Toronto Alexithymia Scale and the NEO Five Factor Inventory, respectively, and their relationship to recognition affect. Subjects with alexithymic characteristics were less able to recognize affective states in posed facial expressions and so may have modified their empathic capacity. PMID- 8197293 TI - Effect of family group psychotherapy on alcoholic families. AB - We examined the effect of family group psychotherapy on 14 alcoholic families. Family group psychotherapy helped alcoholic families be aware of their anxiety and conflict and enabled them to share their feelings with a group. Alexithymia for a cognitive-affective disturbance significantly decreased after group psychotherapy. Moreover, participation in family group psychotherapy over six months increased family cohesion and allowed anxiety and conflict to be more easily expressed within the family. PMID- 8197294 TI - Personality characteristics of very desirable and undesirable childcare workers in a residential setting. AB - Scores on the Sixteen Personality Factor Questionnaire (16 PF) were different for childcare employees designated by their supervisors most and least desirable. This led to a rationale, specific to this setting, which potentially could augment procedures for selection of employees. The methods and cautionary concerns are proposed to other agencies. PMID- 8197295 TI - Association of demographic characteristics, knowledge, and worry about HIV infection with occupational and nonoccupational behaviors of medical students. AB - The authors surveyed a sample of 132 medical students to assess their behaviors related to the risk of HIV infection. Scale measures were computed for survey questions relating to both occupational and nonoccupational behavior and also for questions relating to knowledge of any worry about HIV infection. Regression analysis to assess the influence of demographic characteristics, knowledge, and worry on occupational and nonoccupational behavior indicated that (1) medical students are more likely to implement behaviors to protect themselves from occupational exposure to HIV infection than from nonoccupational exposure and (2) students who worried more about HIV infection reported less at-risk occupational behavior. Implications of these findings for intervention efforts with medical students are addressed. PMID- 8197296 TI - The Psychological Maltreatment Inventory: development of a measure of psychological maltreatment in childhood for use in adult clinical settings. AB - Development of a 25-item Psychological Maltreatment Inventory, based on five categories of psychological maltreatment found in the literature on child development, is described. Two major factors emerged from a factor analytic study of the responses of 118 clinical outpatients. Reported childhood experiences of Emotional Neglect and Hostile Rejection were related to several measures of psychological dysfunction among adult outpatients. PMID- 8197297 TI - Positive changes and worksite health education. AB - 44 of 70 employees attended 7 biweekly sessions during the lunch hour. Assessments of health risk and biometric measurements showed improvement at posttest on exercise, stress awareness, and systolic blood pressure. PMID- 8197298 TI - Parents' beliefs about cholesterol and its effects on their children. AB - A random sample of parents of primary grade children (N = 500) was obtained from two higher socioeconomic-status suburban elementary schools. The respondents (n = 277) were well educated (92% attended or graduated from college), white (92%), primarily higher in socioeconomic status (79% earned more than $50,000/year), and female (70%). Two-thirds of the parents believed that all elementary school children should have their cholesterol levels checked, 70% believed high cholesterol in children was serious, yet only 21% believed their child would develop a high cholesterol level. To control their children's cholesterol level, the majority of parents (73%) made lifestyle changes for their children since the majority believed high cholesterol levels would clog arteries (95%) and cause heart disease (90%). Parents most often received their information on cholesterol from magazines (73%), newspapers (62%), and physicians (52%). PMID- 8197299 TI - Serum cholesterol levels and frequency of aggression. AB - Analysis of serum cholesterol levels of 106 male forensic patients showed significant differences in frequency of aggression, with low cholesterol levels predominant among those more frequently violent. PMID- 8197300 TI - Birth complications and subsequent negative symptoms in schizophrenia. AB - A sample of 29 men with an initial psychotic episode and diagnosis of schizophrenia as young adults were followed into middle adulthood. All had prior child guidance clinic contact. The negative symptoms of affect deficit in young adulthood but not the positive symptoms of thought disorder were predicted by a history of birth complications. Subjects with birth complications who developed negative symptoms had a stable deficit over the follow-up period. PMID- 8197301 TI - Maintained hypersexuality between male rats following chronically induced limbic seizures: implications for bisexuality in complex partial epileptic seizures. AB - Adult male albino rats were given a treatment that produced hypothermia after the induction of limbic seizures by a single subcutaneous injection of lithium and pilocarpine. When housed in groups, these rats exhibited marked hypersexuality (for at least two months), defined as repeated mounting of another male, pelvic thrusting, and persistent genital licking; while the male was mounted, female postures were assumed. There were also periods of physical submission. During active periods three of the four rats were mounted and thrusting in tandem. Possible relevance to the Kluver-Bucy syndrome and to bisexuality and homosexuality in males who report elevated complex partial epileptic-like signs is discussed. PMID- 8197302 TI - Self-reporting of behavior problems in patients with tic disorders. AB - Self-awareness of behavioral or emotional problems was examined in 25 children and adolescents with tic disorders by comparing the Youth, Parent, and Teacher forms of the Child Behavior Checklist. In general, their parents reported a significant number of deviant behaviors which were denied by the patients. PMID- 8197303 TI - Preschool children's seriation of pain faces and happy faces in the Affective Facial Scale. AB - This study was designed to assess the extent to which use by preschoolers of the 1985 Affective Facial Scale by McGrath, et al. is associated with seriation ability and also to examine the number of different distressed and happy facial expressions which can be discriminated and ordered by this age group. 20 boys and 20 girls (mean age 4 1/2 yr.) were recruited from daycare centers. Participants were taught and tested on seriation using a task which required them to rank order nine circles ranging from white to black through grey. Then they rank ordered the nine faces of the Affective Facial Scale. While 39 out of 40 children successfully sorted happy from distressed faces, the present sample was less accurate in distinguishing levels of affect than the older children in the normative sample tested by McGrath, et al. The present participants discriminated only five different levels of facial expression among the nine pictures. Accuracy in rank-ordering the faces was not associated with gender or with performance on the seriation task. Implications for clinical measurement of pain in preschool children are discussed. PMID- 8197304 TI - Needs assessment for a health-promotion program in a medical center. PMID- 8197305 TI - Associations between personality and stress reactions during and after invasion of Kuwait. AB - Correlations between the personality dimensions of extraversion and neuroticism and symptoms of stress reaction during and after the invasion of Kuwait were investigated. An Arabic version of the Eysenck Personality Inventory and a Stress Reactions Checklist were administered to 503 undergraduate Kuwaiti students (225 men and 278 women). Analysis showed no correlation between scores on Extraversion and stress reactions for men and women during and after the invasion and a high positive correlation between scores on Neuroticism and stress reactions for men and women during and after the invasion. These findings were discussed in terms of arousal theory and previous research. PMID- 8197306 TI - Teaching psychopharmacology to psychology interns. AB - A group of psychology interns were given a brief course in psychopharmacology. In follow-up questionnaires from 14 doctoral psychologists 6 months and 2.7 years after graduation respondents stated that the course increased knowledge and confidence in their collaboration with physicians. PMID- 8197307 TI - Self-defeating personality, depression, and pleasure from activities. AB - Prior research has shown people who scored high on a measure of self-defeating personality experienced less pleasure from various activities and accomplishments. The present research replicated the initial study with 55 men and 60 women, while controlling for the effects of depression. Analyses indicated that, while depression and self-defeating personality were related, depression was not the entire answer for why people with self-defeating personality derive less pleasure from activities. PMID- 8197308 TI - A checklist for assessing risk of violent behavior in historically nonviolent persons. AB - Assessment of risk for violent behavior is of interest to clinicians and laymen alike. This article includes a discussion of issues related to assessment of risk of violent behavior. A review of the literature is provided. Using this information, the author suggests several factors that might increase the probability of violent behavior in historically nonviolent individuals, including antisocial behavior, social isolation, poverty, absence of support systems, severe situational stress, and substance abuse. A checklist for assessing risk of violent behavior is suggested. PMID- 8197309 TI - Native American suicide and homicide rates: are they associated with white suicide and homicide rates? PMID- 8197310 TI - Clinically significant cognitive dysfunction in medically asymptomatic human immunodeficiency virus-infected (HIV+) individuals? PMID- 8197311 TI - Anorexia nervosa in a long-term perspective: results of the Heidelberg-Mannheim Study. AB - The long-term outcome of 84 anorexia nervosa patients was studied over a period of 12 years using global clinical ratings and differential physical findings in addition to standardized psychometric measurements. An unusual polarization into good and fatal outcomes was found, with a high recovery rate of 54% and a high mortality rate of 11%. When psychiatric and somatic comorbidity and psychosocial functioning were included in the assessment, the recovery rate was only 41% after 12 years. Clear cases of anorexia decreased steadily from 100% at clinical presentation to 67% after 2 years, 40% after 4 years, and 23% after 6 years. There was almost no further decline after the ninth year of follow-up (17%). Purging, physical symptoms, advanced age at clinical presentation, and a high social status were predictors for an unfavorable course. About 22% of the patients had suffered a relapse after remission. At first presentation, they were young and had a short duration of illness but showed severe psychiatric disorders. Results are discussed in terms of methodological and clinical issues involved in the long-term follow-up of anorexia nervosa patients. PMID- 8197312 TI - Sleep physiological characteristics of exhausted men. AB - Problems initiating and maintaining sleep, and waking up exhausted have been implicated as precursors of a first nonfatal myocardial infarction. These sleep problems are part of an array of complaints that we have labeled as reflecting a state of 'vital exhaustion.' Excess fatigue, loss of vigor, increased irritability, and feelings of demoralization are also characteristic of this state of vital exhaustion, which has been found to constitute a risk indicator for future myocardial infarction. In the present study, we tested the hypothesis that the sleep of exhausted subjects is characterized by a relative absence of slow wave sleep. To test this hypothesis, all-night recordings of the EEG, EOG, and submental EMG of nine exhausted and eight nonexhausted subjects were made for four nights. Sleep stages were rated according to standard criteria. Because these stages do not adequately reflect the essentially continuous aspect of slow wave sleep (SWS), a more detailed analysis of changes in frequencies of the EEG during sleep was also made, using spectral analysis. It seemed that SWS was significantly diminished in exhausted subjects. This suggests that the normal restoration processes that take place during sleep are impaired in exhausted subjects. Additional studies are required to determine the significance of this finding with respect to cardiovascular control during sleep. PMID- 8197313 TI - Depression modulates pruritus perception: a study of pruritus in psoriasis, atopic dermatitis, and chronic idiopathic urticaria. AB - Pruritus, or itching, is the most common symptom of dermatologic disease. Psychologic factors can affect pruritus, and in an earlier study of inpatients with moderate to severe psoriasis, we observed that the degree of depressive psychopathology directly correlated with pruritus severity. In this study we investigated the relation between pruritus and depression among a group of patients (N = 252) with a wide range of pruritic skin disorders, including outpatients with mild to moderate psoriasis (N = 77), atopic dermatitis (N = 143) and chronic idiopathic urticaria (N = 32). All patients self-rated the severity of their pruritus on a 10-point scale and completed a battery of psychologic ratings, including the Carroll Rating Scale for Depression (CRSD). We observed a direct correlation (Pearson's r = .34, p < .0001) between pruritus severity and the CRSD score. The correlations between pruritus severity and CRSD scores for each individual diagnostic group were as follows: psoriasis: Pearson's r = .32, p = .004; atopic dermatitis: Pearson's r = .21, p = .013; and chronic idiopathic urticaria: Pearson's r = .34, p = .06. When the subjects with pruritus scores less than 5.5 were compared with subjects with pruritus scores greater than 5.5, significant differences (p < .05) in depression scores were found for all three dermatoses by the Mann-Whitney U test. The depressed clinical state may reduce the threshold for pruritus. PMID- 8197314 TI - Hostile behavior during marital conflict alters pituitary and adrenal hormones. AB - We evaluated hormonal changes and problem-solving behaviors in 90 newlywed couples who were admitted to a hospital research unit for 24 hours. The subjects were selected on the basis of stringent mental and physical health criteria, and admissions were scheduled during the follicular phase of the woman's menstrual cycle. For frequent, unobtrusive endocrine sampling during the interaction tasks, a long polyethylene tube was attached to a heparin well, allowing nurses to draw blood samples at set intervals, out of subjects' sight. Five blood samples were obtained before, during, and after a 30-minute structured problem-solving or conflict task. The conflict session was recorded on videotapes that were later scored for problem-solving behaviors using the Marital Interaction Coding System (MICS). Marital conflict and MICS-coded hostile or negative behavior during conflict was closely linked to changes in serum hormonal levels across five of the six hormones we studied, in spite of the high marital satisfaction of our newlywed couples and the healthy lifestyles demanded by our exclusion criteria. Hostile behavior was associated with decreased levels of prolactin (PRL) and increases in epinephrine (EPI), norepinephrine (NEPI), ACTH, and growth hormone (GH), but not cortisol. These data suggest that the endocrine system may be an important mediator between personal relationships and health. PMID- 8197315 TI - Family history of hypertension and pain during blood donation. AB - Parental history of hypertension was associated with significantly lower venipuncture pain ratings in women with little or no blood donation experience. Healthy men (N = 288) and women (N = 434) presenting at Red Cross blood donor clinics provided pain ratings in response to an initial blood sample and venipuncture for blood donation. Analyses were restricted to 460 individuals with and without a confirmed parental history of hypertension (N = 188 and 272, respectively). There were no significant gender or parental history effects on initial blood sample pain ratings. Significantly lower venipuncture pain ratings were observed 1) for men vs. women, 2) for more experienced blood donors, and 3) among subjects with 0-1 previous donations, for women with vs. women without a parental history of hypertension. Although pain ratings were positively correlated with subjective anxiety throughout donation, there were no significant differences in anxiety ratings between women with and without a parental history of hypertension. The results provide suggestive evidence of an association between genetic risk for hypertension and decreased pain sensitivity. PMID- 8197316 TI - Parental history of hypertension, menstrual cycle phase, and cardiovascular response to stress. AB - The present study examined whether inconsistent findings for elevated cardiovascular response to stress in female offspring of hypertensives might be a function of 1) lack of control for menstrual cycle phase, and 2) stressor type employed. Thirty healthy women (18-35 years), half of whom were offspring of hypertensives, were tested in both the luteal and follicular phases of the menstrual cycle. Order of testing was counterbalanced between subjects and cycle phase was confirmed by measurement of serum sex hormone levels. In each session, subjects were exposed to four tasks: the cold pressor test, interpersonal speech, shock-avoidance video-game, and reading. The most consistent menstrual cycle effect was for offspring of normotensives who exhibited higher diastolic blood pressure and state-anger responses to the speech task in the follicular compared with the luteal phase. Though menstrual cycle had no consistent effect on offspring of hypertensives, their luteal phase diastolic blood pressure and state anger responses to the speech task were elevated compared with controls. Potential limitations of the observed familial differences in luteal phase response are discussed. PMID- 8197317 TI - Patterns of adrenergic receptors and adrenergic agonists underlying cardiovascular responses to a psychological challenge. AB - Numerous physiological and biochemical factors contribute to the dynamic regulation of the cardiovascular system. This study used a cluster analytic statistical technique to discern patterns of adrenergic receptors and adrenergic agonists underlying cardiovascular responses to a laboratory challenge. Fifty hypertensive and normotensive black and white individuals had their beta- and alpha-adrenergic receptor sensitivity determined through agonist infusions. Norepinephrine, epinephrine, blood pressure, and heart rate responses to a standardized mental arithmetic task were also obtained. The cluster analysis identified four subgroups of individuals having distinct patterns of receptor and neurohormonal regulation of end-organ responses. In general, the data indicated that end-organ cardiovascular responses are, in part determined by the sensitivity of adrenergic receptors and the accompanying catecholamine responses. The findings also suggest that for some individuals nonadrenergic factors play a more dominant role than adrenergic mechanisms in determining cardiovascular pressor responses. PMID- 8197318 TI - Effect of psychosocial stress and age on plasma norepinephrine levels: a review. AB - Forearm venous plasma norepinephrine and muscle sympathetic nerve activity, which are closely correlated, both increase with age. Recent studies have shown that the increase in plasma norepinephrine with aging is confined to long-term cigarette smokers, whereas values in elderly nonsmokers or young smokers were not different from values obtained in young nonsmokers. The mechanism of the increase in plasma norepinephrine in long-term smokers has not been clarified, but cardiac output and plasma volume were not different in smokers and nonsmokers. In patients who have or have had a duodenal ulcer, the increase in plasma norepinephrine with age is markedly increased. These patients tend to die prematurely because of smoking-associated diseases. These patients may select dysfunctional coping strategies like smoking, which may result in organ pathologies and a compensatory increase in plasma norepinephrine. No close correlation has been established between plasma epinephrine and "ill health." High plasma epinephrine levels may have a deleterious effect on the cardiovascular system in elderly subjects during certain conditions. In a population study, however, we found that low resting plasma epinephrine levels were associated with an unfavorable survival rate. We speculate that an inadequate response to psychosocial stress and the choice of dysfunctional coping strategies may be more harmful and cause more "ill health," than hypersecretion of stress hormones like epinephrine and cortisol, which has been the traditional view. PMID- 8197319 TI - Neuropsychological impairment in human immunodeficiency virus-infection: implications for employment. HNRC Group. HIV Neurobehavioral Research Center. AB - Individuals infected with the human immunodeficiency virus-Type 1 (HIV-1), are at increased risk for neurobehavioral impairment, particularly in later stages of the disease. Even patients in the medically asymptomatic or minimally symptomatic stages of infection may show mild deficits on comprehensive neuropsychological (NP) test batteries, although the clinical significance of such deficits remains uncertain. The present study used vocational difficulties as markers of clinical significance of NP impairment. In a sample of 289 HIV-infected, nondemented men, those who evidenced NP impairment had a higher unemployment rate (p < .001) than did their unimpaired counterparts. In HIV-positive subjects who remained employed, NP impairment was strongly associated with subjective decreases in job related abilities. Neither depression nor medical symptoms could explain the relationship between the NP impairment and employment problems. These results are consistent with previous studies investigating other neuropsychiatric disorders, which suggest that even mild NP impairment can interfere with employment status. From this standpoint, such impairment in HIV-infected persons may be described as "clinically significant." PMID- 8197320 TI - [The frequency and duration of psychoanalytic therapy in social insurance settings. Comments on a controversy]. AB - In early 1993 Germany's health care insurance system decided to exclude high frequency analytic therapy involving four to five sessions weekly from the list of medical treatment covered by the health insurance provisions. In the present journal the controversy about the frequency and duration of analytic therapy and the efficacy of high-frequency, long-term analytic treatment as opposed to low frequency psychotherapy has been reflected in the form of a critical commentary (Kaiser, 9/1993) and a review article (Trimborn, 11/1993). Thoma rejects the assumption that high frequency and long duration are invariably necessary conditions for success, advocating greater flexibility in making frequency and duration dependent on the actual changes achieved in the patient's condition by ongoing therapy. The author calls for the employment of differential, "adaptive" indication criteria, his main criticisms being levelled at the form of psychoanalytic training that fails to school young analysts in the selection of the procedures best suited to individual patients. As it is a generally accepted fact that psychic changes take time, the author concludes that successful therapy is not a matter of frequency but a function of extension over time, thus making duration of therapy the operative factor. PMID- 8197321 TI - [Pragmatism or methodology? Psychoanalytically oriented 10 session counseling within the scope of supervision]. AB - Contrary to the widespread opinion that a short-term setting can do little more than provide purely cognitive insights, Scharff demonstrates that such a setting can indeed provide a significant initial understanding of psychodynamic processes. In the author's view the matter hinges on three things: a well-defined psychoanalytic stance; a psychoanalytic understanding; and a psychoanalytic approach to those coming for counsel. If the supervisor displays a methodologically clear-cut psychoanalytic approach, the counsellor will gain confidence in his feelings of counter-transference and this will enable him to use these as an analytic instrument and put his finger on the unconscious facets of the central conflict affecting the client. In the author's view, concepts such as projective identification, unconscious role-assumption and action dialogue are of special significance for the understanding of psychodynamics. A vast range of different aspects of 10-hour counselling are demonstrated with reference to a variety of examples. PMID- 8197322 TI - [Phenomenology of depression from the psychoanalytic viewpoint]. AB - From the abundance of psychoanalytic theories of depression the author establishes five characteristic types of depression on the basis of the cardinal symptom represented by the nature of the feelings prevalent in each case. Will makes no claim to advancing a unified theory but draws upon existing theoretical concepts to describe the following types of depression: super-ego depression; oral-dependent depression; ego depression; narcissistic depression; realistic creative depression. There is also an initial brief discussion of the general characteristics of depression. PMID- 8197323 TI - A study of the area of distribution of the deep sensory neurons of the human ventral thalamus. AB - During neurosurgical treatment for the relief of movement disorders, thalamic neurons were identified with activity related to passive joint movement, active joint movement, deep sensory stimulation and superficial sensory stimulation. The cells responding to passive joint movement were located just rostral and dorsal to the cells responding to superficial sensory neurons. This area corresponded not only to Hassler's Vim (ventralis intermedius) nucleus but also to a part of the Vc (ventralis caudalis) nucleus. This distribution mode of cells responsive to passive joint movement was similar to that of the deep sensory neurons in the VPLo (ventralis posterior lateralis oralis) nucleus and in a portion (anterodorsal shell) of the VPLc (ventralis posterior lateralis caudalis) nucleus in the monkey thalamus. Recently, the anatomic and physiologic similarity between the human and monkey thalamic ventrolateral complex has been described. These results confirm the similarity between the human and monkey thalamic ventrolateral complex both anatomically and physiologically and could thus be useful for future studies exploring the neuronal mechanisms of involuntary movement disorders, such as tremor. PMID- 8197324 TI - Trajectory angle in stereotactic thalamotomy. AB - Most neurosurgeons use a frontal burr hole in stereotactic thalamotomy for movement disorders. However, the reports on this operation show a variation in trajectory with reference to the angles to the intercommissural line and the midsagittal plane. We studied the effect of the trajectory angles on operative results in 22 patients who underwent stereotactic thalamotomy for tremor control. The angle varied between 28 and 71 degrees (mean 44 +/- 10) in the sagittal plane, and between 0 and 25 (mean 11 +/- 7) in the coronal plane. There was linear correlation between the angles and the distances of a burr hole from the coronal suture and the midline. However, the angles did not show any correlation with the number of target corrections required, the size of the lesions made, tremor control and the incidence of complications. These findings indicate that the trajectory angle does not play an important role in stereotactic thalamotomy. PMID- 8197325 TI - Registration of EEG electrodes with three-dimensional neuroimaging using a frameless, armless stereotactic wand. AB - A technique of image and electrode registration has been developed that allows electroencephalogram electrode location to be merged with 2-D or 3-D MRI or CT. An armless, frameless stereotactic localization system that may be used in or out of the operating room is used to generate spatial data for surface and accessible intracranial electrodes. Acquisition of electrode position data may be obtained before or after neuroimaging and the locations of additional electrodes added at any time. The methodology of this system and representative cases with MRI imaging are presented. PMID- 8197326 TI - A simple system for stereotactic volumetric resection. AB - Stereotactic volumetric resection of deep-seated intracerebral lesions is generally believed to require expensive and complex facilities. The authors report a simple system for stereotactic craniotomy, in which the software in the computed tomographic scanner and a personal computer are used for preoperative planning and intraoperative orientation. PMID- 8197327 TI - The thalamocingular loop: recordings from the past. AB - It has been shown recently that a portion of the cingular cortex (area 24) is involved in the perception of pain. Older electrophysiological studies in neurosurgical patients, which could not be explained on the basis of previous anatomical data, support this notion. PMID- 8197329 TI - Experience with 509 plate electrodes implanted epidurally from C1 to L1. AB - This article summarizes the experience gained with implantation of 509 plate electrodes performed by a single neurosurgeon. 350 patients were subjected to implantation of plate electrodes in the dorsal epidural space. 227 patients were implanted for chronic pain management (reflex sympathetic dystrophy, failed back syndrome/arachnoiditis, pain following spinal cord injury, nerve injury pain and other miscellaneous pain conditions), 105 patients for motor disorders (spasms/spasticity following spinal cord or head injury, cerebral palsy, multiple sclerosis, spasmodic torticollis and other miscellaneous conditions) and 18 patients for both. A total of 509 electrodes were implanted in the dorsal epidural space. The electrodes types were: 442 Medtronic Resume, 39 Medtronic Resume-TL and 25 Neuromed Lamitrode. 378 electrodes were implanted for chronic pain management, 106 for motor disorders and 25 in patients presenting with both pain and motor disorders. 192 electrodes were implanted in the cervical area and 317 in the thoracic area. 3.7% of the implanted electrodes became infected and had to be surgically removed. Electrode migration occurred in 1.1% of the patients and electrode breakage in 4 patients. 288 (70%) of the implanted electrodes are still being used. Technical factors relevant to the surgical implantation of plate electrodes at various levels in the spine are presented and discussed. PMID- 8197328 TI - Neuroelectric stimulation in cerebral palsy: long-term quantitative assessment. AB - Results from multiple tests including somatosensory evoked potentials, passive resistance to motion, upper extremity motor skills evaluation, neuromuscular examination, and parental interview were evaluated in 13 children with cerebral palsy (CP) who received chronic cerebellar stimulation (CCS) for reduction of spasticity and movement disorders during the past 14 years. The prospective study included immediate postoperative follow-up data as well as longer term results from the quantitative test series. Although CCS was effective in reducing hypertonicity in CP children during the immediate short-term, the diminishment waned significantly 3-5 years postoperatively. PMID- 8197330 TI - Nonvolumetric stereotaxy-assisted craniotomy. Results in 50 consecutive cases. AB - Craniotomy using stereotactic techniques has the potential to improve the extent of tumor resection and to reduce wound and neurologic morbidity. Most reports of stereotaxy-assisted craniotomy (SC) for tumor resection have focused on techniques using sophisticated computer hardware and volumetric software. Results of nonvolumetric SC in 50 consecutive cases for tumor using the Brown-Roberts Wells or Cosman-Roberts-Wells stereotactic systems are presented. Tumor type included malignant glial neoplasms (20 cases), metastases (19), benign glial tumors (5), meningiomas (4), and radiation necrosis (1). Results in the SC group were compared to a concurrent series of 50 conventional craniotomies (CC) for brain tumor by other surgeons. Sustained neurologic deficits were 4% in the SC group while 10% for CC. Wound complications were 4 and 8%, respectively. Median hospital stay was 5 days (mean 5.9, range 2-20) for SC and 7 days (mean 10.4, range 3-75) for CC. Low morbidity resections of many brain lesions can be performed using conventional stereotactic systems, the operating microscope and standard CT software. PMID- 8197331 TI - Changes in arterial blood pressure induced by percutaneous thermocoagulation of the trigeminal ganglion and rootlets. AB - The changes in arterial blood pressure which occur during the different steps of thermocoagulation of the trigeminal ganglion and rootlets are reported. The arterial blood pressure of 54 patients with trigeminal neuralgia was recorded continuously by catheterization of the radial artery. The maximal values were recorded (a) during the analgesic-sedation stage; (b) when the electrode came into contact with the base of the cranium during movement of the needle towards the foramen ovale; (c) during insertion of the electrode into the foramen ovale, and (d) during the thermocoagulation. One-way analysis of variance and Student's t test were used for analysis of the data. There was a significant increase of arterial blood pressure during the various stages of thermocoagulation. PMID- 8197332 TI - Management of staghorn calculi: percutaneous nephrolithotripsy versus extracorporeal shock-wave lithotripsy. PMID- 8197333 TI - Differing modes of shock-wave generation. PMID- 8197334 TI - Should one perform open surgery in 1994? PMID- 8197335 TI - Ureteroscopic stone retrieval: rigid versus flexible endoscopes. PMID- 8197336 TI - Modes of intracorporeal lithotripsy: ultrasound versus electrohydraulic lithotripsy versus laser lithotripsy. AB - It seems apparent, from the previous discussion, that no form of intracorporeal lithotripsy represents the perfect treatment modality for all upper urinary-tract calculi. In fact, the role of endoscopic techniques for treatment for upper-tract calculi must be carefully considered given the success of SWL. However, not all stones are amenable to extracorporeal treatment. Therefore, ureteroscopy, with the various forms of intracorporeal lithotripsy, represents an alternative means for successfully treating patients without having to resort to surgical intervention. Ultrasonic lithotripsy is probably the least preferable of the three forms of treatment, primarily because it must be carried out with rigid endoscopic equipment. In the future, if flexible or semirigid devices can be developed, ultrasonic lithotripsy may become a more useful option for the treatment of ureteral calculi. Laser lithotripsy and EHL seem to be equally well suited for use with flexible, actively deflectable ureteroscopes. The relative risks and benefits of these two modalities make their use a matter of clinician's choice. The greater risk of ureteral injury may make EHL somewhat less attractive to endoscopists. However, this must be balanced with the increased cost of the laser lithotripter. It has become apparent that a direct comparison of these three types of intracorporeal lithotripsy is difficult because of the lack of standardized data and the scarcity of randomized comparative trials. Despite this, it appears that all three forms of intracorporeal lithotripsy play an integral part in the treatment of upper-tract urinary calculus disease. Certainly, one of the more exciting areas in the field of endourology will be the continued emergence and development of new technologies and devices for these purposes. PMID- 8197338 TI - [Survival at what price? Ethical problems in neonatal intensive care medicine]. PMID- 8197337 TI - Is there a need for medical evaluation and treatment of nephrolithiasis in the "age of lithotripsy"? PMID- 8197339 TI - [The very small premature infant. Ethical problems from a neonatology viewpoint]. AB - The opening text of the conference provides a summary of the definitions, the probabilities, the mortality rate, the postnatal risks and the perspectives for life of very small newborn babies. The best indicator for the later development of the child is the length of gestation and the birth weight. The care of the parents themselves is very important, as they are going through a very difficult period of changing emotions, anxiety, guilt, joy and grief. The further development of the child can only be forecast with probabilities and not with certainties; therefore, every decision for or against the life of a prematurely newborn baby can be either correct or incorrect. The place for taking this kind of decision is within the team caring for the baby. The difficult process of decision-making and its responsibility cannot be handed over to the parents. The final responsibility lies in the hands of the physician. PMID- 8197340 TI - [Therapy in unfavorable prognosis. Ethical dilemma in the treatment of newborn infants with severe abnormalities]. AB - The doctor treating a baby destined to be handicapped with certainty has to find a way between the two extremes of overtreatment and selective medicine. Medico ethical directives cannot replace personal commitment in this process. The observation of the jargon used in team discussions can reveal tendencies to one or the other extreme position. An attitude is proposed that tries to balance the gain in joy of life, in possibilities for human relations and in experience of life, the start or pursuit of a therapeutic measure possibly allows against the pain, discomfort and deprivation it inevitably entails. PMID- 8197341 TI - [Limits of intensive care--decision making on the way between life and death]. AB - Survival and death are closely related in intensive-care medicine. Both have to be accepted and accounted for when decisions have to be made and activity is required. Only then a sound and truthful process of decision-making is guaranteed. Both, the experienced as well as the novice, need guidelines in this process. The basis of these guidelines lies in quite different aspects of life: juridical, philosophic-ethical and religious. The first part of this paper focuses on the specific setting of neonatal intensive care. Three issues must be considered: The patient is not the direct partner in conversation; illness and its consequences have an impact on the social network of the whole family; mothers quite often suffer from severe guilt feelings, which have to be understood and addressed. The second part describes the essential elements of support on the journey' between life and death. They can be summarized under seven headings: urgent acquisition of all necessary data; the need for medical intervention before optimal level of relevant information is available; the importance of allowing for human time factors; the process of arriving at certain decisions; the dealing with unexpected changes in the course and development of the disease; the cessation of therapy; the parental support in bereavement. The overall emphasis of medical intervention should be to view the patient as human being, not as a treatable subject amongst a setting of numerous medical intervention techniques. PMID- 8197342 TI - [Our possibilities and limitations in the care and management of severely ill premature and newborn infants]. AB - Even normal care of prematurely newborn babies in neonatal intensive-care unit can be critical for them. It is within the responsibility of the nurse to decide how much care is possible and how much rest the children require. An important part of the work of the nurse is the care of the parents. Usually the child has been taken away from the parents immediately after labour and delivery. Often the mother is in an other hospital (and cannot yet be moved); thus, the nurse becomes a mediator between the parents and the child. The decision to stop treatment is very difficult for all concerned. In this difficult situation parents need the input and support of the nurses who know their children best. More creativity is needed for the development of new ideas in the care for prematurely or handicapped newborn babies. Additionally more attention to the desires of the parents should be given. PMID- 8197343 TI - [Possibilities and limitations in the nursing care of severely ill premature and newborn infants]. AB - Working as a neonatology nurse means not only taking care of the very little and sometimes critically ill patients, but also means being confronted with ethical problems. High-tech medicine, we hope, to help our little patients, but can also irritate and endanger their sensible system. That puts us before the question: If it makes sense to use every medical possibility? These conflicts can bring problems into the team of nurses, doctors and parents. It is our aim that we have the time and space to confront such problems and to find solutions. PMID- 8197344 TI - [Legal aspects (with comparative reference to German Law)]. AB - Considering the improved medico-technical possibilities, the treatment of handicapped newborns has weighty consequences for all interested persons. But 'letting die' these infants can never be a solution for this problem. It is not possible to find a reliable test for an authorized withdrawal of vital treatment. The law has to require that medical treatment is carried out in all cases in which the infant is viable with medical support. In exceptional cases the prosecution of the responsible persons can be relinquished. PMID- 8197345 TI - [Ethical observations concerning the limitations of medical duty to treat in severely handicapped neonates]. AB - The author places the new treatment options of neonatal intensive care units into the framework of modern medicine in general. Paradoxical situations emerge. In one section of the hospital, premature newborn babies are treated in the intensive-care unit, and in another section others are selected for abortion. A late interruption is often an early labour and delivery. The right to live for every person is formulated in the text. The problems concerning viability and perspectives for life of premature or handicapped newborn babies makes it impossible to formulate a list of situations in which the duty to treat can be disregarded. The only treatment limit is complete brain-death. The parents of the child are the ones most affected by its disabilities; therefore, they must be included in the process of decision-making. There is no right for a healthy child, but a right of the child for acceptance and appropriate care by parents and a stable society. PMID- 8197346 TI - [Survival at what price? Ethical problems in neonatal intensive care medicine- observations on a round-table discussion]. AB - Infants with a very low birth weight (below 1250 g) have a high risk to develop handicaps later. Though it is not possible to make a final prognosis for the infant's future, we have to weight the benefits and side effects of our interventions. This may lead to the decision not to continue with intensive-care treatment. We not only have to care for the patients while they are in our unit, it is of equally great importance to support the whole family after the discharge from the hospital. PMID- 8197347 TI - [An infallible method of treating sacrococcygeal cysts]. PMID- 8197348 TI - [The treatment of combined digital-palmar injuries]. AB - Different treatment modalities for palmar combined injuries of the fingers are described. Several possibilities are mentioned for each traumatized structure which can be involved in such injuries. Early functional after-treatment is emphasized, which usually needs stable reconstruction for all injured components (skin, nerves, arteries, fractures, joints, flexor tendons and pulleys), so as to allow immediate active mobilization. The results of palmar combined injuries of 178 fingers in 150 patients, treated from September 1986 to May 1991 at the Division of Hand Surgery, University of Bern, Switzerland, offer the more recent experience for the favoured handling of such injuries. The results were collected and statistically analyzed to seek for mutual interactions in the healing of the different structural components. PMID- 8197349 TI - [Principles of immobilization of and equipment for the hand]. PMID- 8197350 TI - [Stable elastic nailing of fractures in children]. PMID- 8197351 TI - [Progress in the treatment of rupture of the anterior cruciate ligament]. PMID- 8197352 TI - [Standard radiological study of the knee]. PMID- 8197353 TI - [Extra-articular manifestations of rheumatoid arthritis at the time of basic methotrexate treatment: apropos of a case of nodulosis with pericarditis]. PMID- 8197354 TI - [Management of a patient: viewpoint of the general practitioner]. PMID- 8197355 TI - [Hyperthyroidism then hypothyroidism at the end of a painful swelling of the thyroid: autoimmune thyroiditis or De Quervain thyroiditis?]. PMID- 8197356 TI - [Development of bacterial species and their sensitivity to antibiotics in the laboratory of a small hospital]. PMID- 8197357 TI - [Clinical usefulness of phenotyping of alpha 1-antitrypsin]. AB - Analysis by isoelectric focusing of serum alpha 1-antitrypsin phenotype of 167 consecutive cases from an occupational health outpatient clinic, from university hospital departments and from private practitioners showed an excessive presence of rare gene alleles S, Z, I and anodal variants compared to their frequencies in blood donors from Lausanne or in the general Swiss population. It seems that analysis has been well grounded in most cases and helps to establish diagnosis in many respiratory diseases, in unexplained liver cirrhosis and even in aortic rupture. PMID- 8197359 TI - [Music: art and therapy]. PMID- 8197358 TI - [History of a climatology station, Montana, Canton of Valais]. PMID- 8197360 TI - [The raw and the cooked]. PMID- 8197361 TI - [Toward a renaissance of clinical medicine]. PMID- 8197362 TI - [Daily ethics]. AB - 2nd and 3rd year students of a nursing school of Torino (north of Italy) were asked to collect critical incidents occurred during their practical training. The requirement of the critical incidents to be reported, was the identification of ethical-deontological implications for the student. The critical incidents were then written according to predefined criteria and discussed in the classroom during the ethics lesions. Nursing students collected 131 critical incidents, classified in 12 categories. Some general comments both on the method and on the overall scenario of the practice are presented. PMID- 8197363 TI - [Knowledge about HIV infection in a group of professional nursing students]. AB - A confidential questionnaire was given to 241 students of the nursing school of a Milano Hospital to record the knowledge on HIV infection and their experience with HIV patients during their training in wards different from Infectious Departments. The results evidence a good level of knowledge, comparable to the italian young population (according to other studies) of the same age. Nursing students from the very beginning of their practical training, happen to care for asymptomatic HIV positive subjects, therefore the school should provide knowledge and information on the HIV infection before the beginning of the practical training. PMID- 8197364 TI - [Obvious matters: more or less]. PMID- 8197365 TI - [The methods and instruments of nursing research: an analysis of some articles]. AB - Research papers published on some of the most well known nursing journals are presented and discussed. The main aim of the contribution, which opens a new arena for discussion on the Rivista dell'Infermiere is to critically appraise published research works focusing both on strengths and novelty and weaknesses in the hypothesis formulation, methods and instruments used, discussion of results. A critical analysis should enable nurses to start learn to read and eventually write a research protocol, possibly avoiding some common mistakes. PMID- 8197366 TI - [The treatment of oral cavity problems: a review of the literature]. PMID- 8197367 TI - [The Bhopal tragedy: 10 years later]. PMID- 8197368 TI - [The reform of reform: the implications for health]. PMID- 8197370 TI - [Monitoring a home care program]. PMID- 8197369 TI - [The decalogue of the post-manual]. AB - On the 1st January the Italian Health Ministry published a new Drug List, where marketed pharmaceutical products had been re-classified by the ad hoc Commission (CUF, Commissione Unica del Farmaco). Drugs were divided in three categories: A. effective drugs (drugs able to prolong life or improve quality of life), provided by the NHS without any charge for the consumer; B. drugs whose therapeutic role is less "critical", and or could be a second option, for which the consumer is expected to pay 50% of the price; C. compounds without any documented efficacy, not reimbursed by the NHS. H. drugs to be prescribed only by the hospital services. One of the key members of CUF proposed a comprehensive evaluation of the work done, which has been seen as a "revolution", with hot debates from all concerned parties (including the strong opposition from the pharmaceutical industry and private pharmacists). Overall, the number of efficacious drugs freely available for the majority of patients has tripled, while the exclusion (into class C) of many (often very expensive) useless drugs is expected to decrease the overall public drug expenditure. PMID- 8197371 TI - [Urinary incontinence. Its prevalence among female health professionals]. PMID- 8197372 TI - [The nursing interview. Something more than just data collection]. PMID- 8197373 TI - [Social skills. Training in a nursing school]. PMID- 8197374 TI - [User satisfaction. The determining factors]. PMID- 8197375 TI - [Batteries and health]. PMID- 8197376 TI - [The Prenatal Study Center]. PMID- 8197377 TI - [The patient in the operating room]. PMID- 8197378 TI - [Dying at home. The role of the community nurse]. PMID- 8197379 TI - [Evaluating the patient with orthopedic problems]. PMID- 8197380 TI - [Drainage devices. For the effusions from fistulas and wounds]. PMID- 8197381 TI - [A health education plan in nutrition]. PMID- 8197382 TI - [Where are the health professions going?]. PMID- 8197383 TI - Ethics in action: a nurse has noticed in the past several weeks that the performance of a colleague with whom she's worked for many years is slipping. PMID- 8197384 TI - Central lines have moved out. PMID- 8197385 TI - Safe suctioning prn. PMID- 8197386 TI - Caring and curing. PMID- 8197387 TI - Caring and comforting. PMID- 8197388 TI - Emergency cardiac care: new pediatric guidelines. American Heart Association. PMID- 8197389 TI - FDA approved new drug bulletin: torsemide (Demadex), trimetrexate glucuronate (neuTrexin). PMID- 8197390 TI - Focusing on outcomes. PMID- 8197391 TI - Home care: more autonomy, more legal risks. PMID- 8197392 TI - Zidovudine reduces HIV transmission from mother to infant. PMID- 8197393 TI - Don't assume the patient was noncompliant. PMID- 8197394 TI - An open letter to my colleague, my mentor--my mom. PMID- 8197395 TI - A unique view of patients who've had a stroke. PMID- 8197396 TI - Angiotensin-converting enzyme in human skeletal muscle. A simple in vitro assay of activity in needle biopsy specimens. AB - The importance of skeletal muscle for human haemodynamics and metabolism makes it a suitable sample tissue for the measurement of angiotensin converting enzyme (ACE; EC 3.4.15.1). A study of serum and muscle angiotensin-converting enzyme was performed in 50 essential-hypertensive subjects. Muscle tissue was obtained from the vastus lateralis muscle by Bergstrom needle biopsies. The method used is a modification in Cushman's fluorometric assay for tissue angiotensin-converting enzyme. It utilized 5 mM hippuryl-histidyl-leucine as a synthetic substrate for a 60-min fixed-time incubation at 37 degrees C. The 0.25 ml incubation mixture consisted of 0.12 mM potassium phosphate buffer, pH 8.1, 300 mM NaCl, and 1 or 2 mg homogenized muscle tissue. The activity was found to have the properties previously reported for human ACE. The intra- and interassay coefficients of variation of the method were 13% and 21%, respectively, for the 1 mg incubation as assessed from internal controls (n = 20). the muscle ACE activity in the hypertensive subjects was 49 +/- 14 mU g-1 (mean +/- SD) with no difference between values for men and women. No correlation was found between muscle ACE activity and age, or between muscle and serum angiotensin-converting enzyme activity. We consider this assay a useful new tool for investigating the role of angiotensin-converting enzyme in the pathogenesis and treatment of hypertension, as it can be applied to patient materials. PMID- 8197397 TI - Reliability of C-reactive protein measurement in general practice in The Netherlands. AB - The aim of this study was to compare the reliability of the whole blood NycoCard C-reactive protein measurement (CRP) with the erythrocyte sedimentation rate (ESR) in four general practice centres (GPCs) in The Netherlands with 443 patients indicated for ESR. During 4 successive months in 1992 NycoCard CRP was measured in capillary (whole) blood at the GPC. A venous blood sample was then transported to the local hospital laboratory in order to determine CRP turbidimetrically in plasma. Westergren's ESR was measured at the GPC and at the laboratory. The dichotomized CRP values measured at the GPCs corresponded with the laboratory values in 88% of the cases. Kappa was 65% (p < 0.00001). Using a 20 mm cut-off point, ESR values measured at the GPCs and the laboratory corresponded in 96% of cases (Kappa = 90%, p < 0.00001). Interpractice variabilities and learning effects did not influence the results. 'False normal' rates for CRP and ESR were 8% and 1%; 'false elevated' rates were 28% and 12% respectively. The reliability of the NycoCard CRP measurement in whole blood disappointed. In particular the 'false elevated' rate is unacceptably high for daily general practice. The background of the poor reliability remains unclear. PMID- 8197398 TI - Intravenous theophylline-induced excretion of calcium, magnesium and sodium in patients with recurrent asthmatic attacks. AB - Hypomagnesaemia in a woman treated with theophylline and albuterol because of recurrent asthmatic attacks prompted us to explore the effects of these drugs on the metabolism of magnesium, calcium, sodium and phosphate in such patients. Theophylline given intravenously to 10 females with recurrent asthmatic attacks increased total mean urinary excretion (mean +/- SEM, mmol 5 h-1) of Mg from 0.54 +/- 0.07 to 0.86 +/- 0.10; of Ca from 0.89 +/- 0.18 to 1.45 +/- 0.26; of Na from 22.9 +/- 7.5 to 49.4 +/- 9.5. Theophylline i.v. and an inhaled beta 2-agonist (albuterol) both increased the normal morning-till-noon serum concentration difference (mean +/- SEM, mmol l-1) in PO4 (from -0.13 +/- 0.04 to - 0.23 +/- 0.03 and -0.23 +/- 0.04, respectively) and reduced the normal increase in serum-K (from 0.25 +/- 0.07 to 0.06 +/- 0.08 and -0.13 +/- 0.09, respectively). Disproportional changes in serum and urinary levels of magnesium and calcium by theophylline i.v. is suggestive of Mg depletion of intracellular stores and a negative calcium balance. Theophylline, therefore, may exert adverse effects on the metabolism and urinary excretion of calcium and magnesium in subjects with recurrent asthmatic attacks. PMID- 8197399 TI - The effect of in vitro procedures on cyclic AMP accumulation in human leucocytes. AB - The aim of this study was to investigate the effect of various methodological procedures or protocols on cyclic AMP formation in human leucocytes. The data showed that: (1) ATP content and lactate production was unaffected by hypotonic lysis during leucocyte isolation; (2) there was a linear relation between cell number/sample and the production of cyclic adenosine 3':5'-monophosphate (cAMP); (3) the interindividual variation markedly affected cAMP production during long observation periods (years), whereas day-to-day variation within a week was less important; (4) whole blood could be stored for up to 4 h (at 4 degrees C or 23 degrees C) without affecting cAMP accumulation; (5) isolated MNL could be stored for up to 2 h (at 4 degrees C) without affecting cAMP accumulation; and finally that (6) choice and concentration of phosphodiesterase inhibitors markedly influenced the basal and isoprenaline-induced cAMP accumulation. Evidence is provided that the rate of cAMP accumulation in response to isoprenaline of cells incubated in the presence of 2.5 mM 3-isobutyl-1-methyl-xanthine (IBMX) is reflecting the rate of cellular cAMP production. PMID- 8197400 TI - Reference intervals and decision limits for plasma lipids and lipoproteins: a practical evaluation of current recommendations. AB - As part of a longitudinal study--the Kristianstad Survey--we measured plasma cholesterol, HDL- and LDL-cholesterol, triglycerides and lipoprotein (a) in a reference group consisting of 203 men and women aged 20-80, randomly sampled from a well-defined area in the southernmost part of Sweden. The selection of reference individuals and the collection of specimens for assay of the constituents were performed in accordance with current recommendations. The results were subjected to statistical analyses both with and without application of exclusion criteria. Application of the theoretical exclusion criteria resulted in the exclusion of 22% of the participants; however, this procedure had a remarkably weak impact on the results: the mean values and the standard deviations were almost unaltered. The mean (standard deviation) for cholesterol was 5.9 (1.3) mmol l-1, for HDL-C 1.1 (0.3) mmol l-1, and for LDL-C 4.3 (1.2) mmol l-1. Women had higher values than men. Plasma triglycerides were positively skewed; their median and Q3-Q1-values were 1.0 and 0.5 mmol l-1 respectively, men higher than women. There was an increase with age for cholesterol and LDL-C in both sexes and for triglycerides in women. The steepest increase of cholesterol values with age in women coincided with menopause, which have a more clear-cut separation between high and low cholesterol values than did any age limit. PMID- 8197401 TI - Susceptibility to in vitro lipid peroxidation of low density lipoproteins and erythrocyte membranes from liver cirrhotic patients. AB - The aim of the present study was to investigate the susceptibility of low density lipoprotein (LDL) and red blood cell membranes (RCM) from liver cirrhotic patients and control subjects, to the peroxidative stress, induced in vitro by phenylhydrazine. The susceptibility to peroxidation was determined by measuring the formation of the thiobarbituric acid reactive substances (TBARS) after incubation with phenylhydrazine. Moreover the levels of cholesterol (C) and phospholipid (PL) were evaluated in plasma and isolated LDL and RCM. A significant decrease in plasma C, LDL-C and RCM-C content (p < 0.001, p < 0.01 and p < 0.05 respectively) and RCM-PL content (p < 0.01) were found in cirrhotic patients compared to controls. The lower susceptibility to in vitro peroxidation was shown by the TBARS levels significantly lower in LDL and RCM from cirrhotic patients with respect to controls (p < 0.0001 for both of them). Moreover significant positive correlations were found between TBARS-LDL and LDL-C or LDL PL (r = +0.72, p < 0.0001; r = +0.58, p < 0.001) and between TBARS-RCM and RCM-C (r = +0.35, p < 0.05) or RCM-PL (r = 0.37, p < 0.05) from combined patients and controls. Our data seem to ascribe the lower in vitro peroxidability to the lower levels of plasma lipids. PMID- 8197402 TI - The acute effects of induced tachycardia on coronary sinus and arterial plasma levels of atrial natriuretic peptide and on arterial catecholamines. AB - Atrial natriuretic peptide (ANP) was measured in coronary sinus (CS) plasma in seven patients with induced tachycardia. Right atrial pressure (RAP) and femoral artery (FA) levels of ANP, noradrenaline (NA) and adrenaline (A) were measured before and after 5 min with tachycardia. During tachycardia, ANP in CS plasma increased from 381 +/- 273 (mean +/- SD) to 1376 +/- 1191 pmol l-1 (p < 0.0001), and ANP levels in FA plasma from 89 +/- 48 to 231 +/- 151 pmol l-1 (p < 0.005). A significant increase was observed for peak RAP, whereas mean RAP remained unaltered. While no correlation existed between the increase in CS plasma ANP level and RAP, significant correlations were found between the changes in FA plasma ANP and RAP, and between FA plasma levels of ANP and NA. Following tachycardia, significant correlations were found both between ANP in CS and FA plasma and between the changes in these plasma levels. Whereas the changes in FA plasma levels of ANP during tachycardia seems dependent of RAP and arterial plasma levels of NA, the CS plasma ANP level appears to be independent of the two factors, probably because CS plasma ANP are drained mainly from the left side of the heart. PMID- 8197403 TI - Diurnal variations in total forearm and skin microcirculatory blood flow in man. AB - The aim of the present study was to determine diurnal variations in total forearm and skin microcirculatory blood flow in healthy man. At six time points between 08.00 and 18.00 hours was measured: blood pressure, forearm blood flow (FBF; strain gauge plethysmography), skin thermoregulatory blood flow (LDF; laser Doppler fluxmetry), and skin nutritive blood flow (CBV: Capillary Blood Cell Velocity; intravital capillary microscopy) in 15 healthy, fasting, and resting men. FBF increased gradually from 2.8 in the morning to 4.3 ml 100 ml min-1 in the afternoon (p < 0.001). In contrast, LDF decreased, predominantly in the morning, from 18.3 at 09.00 hours to 13.1 at 12.00 hours and to 12.1 perfusion units at 17.30 hours (p < 0.001). However, performing the same protocol starting in the afternoon resulted in a similar initial decrease in LDF, suggesting an acclimatization phenomenon. Although not statistically significant, the decrease in CBV showed a similar pattern as compared to LDF. Blood pressure did not change. In conclusion, forearm blood flow increased during the day, probably due to diurnal variation in muscle flow. The initial decrease we observed in skin thermoregulatory blood flow is probably not related to diurnal variation but due to long-term acclimatization to the experimental conditions. These data suggest different regulatory mechanisms for the different vascular beds studied. Measurements of forearm blood flow should preferably be performed at the same time of day, and skin microcirculatory haemodynamic measurements should be performed after a standard period of acclimatization. PMID- 8197404 TI - Do local hospitals meet the analytical goals for the use of common reference intervals? AB - Blood samples were obtained from 183 blood donors and measured in two hospitals in the same geographical area using identical reference intervals and measuring equipment. The analytical bias of the clinical chemical analyses was investigated through paired measurements. The results showed that out of 15 routine analyses only four meet the goals for acceptance of common reference intervals, of which at least three were of clinical significance. The problems were reflected in the quality assessment results but, nevertheless, no action seems to have been taken. PMID- 8197405 TI - Non-obese men with high lipoprotein(a) values--a cardiovascular risk group different from those with the metabolic syndrome? AB - We have investigated the prevalence of cardiovascular risk factors including insulin and lipoprotein(a) in 40-year old men from the island of Oland (n = 314, 84% of those invited) in order to assess to what extent insulin and lipoprotein(a)--two of the currently discussed risk factors--correlated with each other, as well as with some of the more established risk factors. An inverse correlation was found in bivariate analyses between lipoprotein(a) and some of the risk factors for cardiovascular disease included in the 'metabolic syndrome' (triglycerides; r = -0.15, BMI; r = -0.18, and insulin/glucose ratio; r = -0.18) (p < 0.001). In multivariate analysis only the inverse correlation with triglycerides remained. Since lipoprotein(a) has been shown to be an independent risk factor for myocardial infarction, there may exist two subgroups of cardiovascular risk patients: one more obese, hyperinsulinaemic and with several metabolic derangements; and another comprising non-obese subjects with higher lipoprotein(a) values. PMID- 8197406 TI - Effect of clotting temperature and eosinophil concentration on the eosinophil cationic protein concentration in serum. AB - Earlier investigations have indicated the need for detailed instructions about the incubation conditions of blood samples before establishment of eosinophil cationic protein concentration in serum. Therefore, the effect of different clotting temperatures and eosinophil concentrations on the serum eosinophil cationic protein concentration was quantified in 40 subjects. Our results show that serum eosinophil cationic protein concentrations strongly depend on the clotting temperature. Blood samples clotted for 1 h at 37 degrees C had 5-10 times higher serum eosinophil cationic protein concentrations than blood samples of the same subject clotted for 1 h at 0 degrees C. Higher eosinophil counts resulted also in increased serum eosinophil cationic protein concentrations. PMID- 8197407 TI - Hereditary spherocytosis: diagnostic and anaemia-associated aberrations of ghost proteins. AB - Various disorders of the red cell skeleton and membrane have been described in hereditary spherocytosis. To elucidate which aberrations could be used for identification of HS patients in a Danish population, we examined ghosts from 17 HS patients and 20 normals by use of SDS-gel scanning, native spectrin extraction, and limited tryptic digestion. Compared to normals, HS patients had significantly lowered alpha-spectrin (p < 0.004), protein 4.2 (p < 0.025), and actin (p < 0.05), and significantly increased anion-transporter (p < 3 x 10(-6)) and glyceraldehyde-3-phosphate dehydrogenase (G3PD, p < 0.04). Sixteen out of 17 HS patients could be identified by aberrations of the anion-transporter or protein 4.2 outside a 95% confidence interval for normals. Extraction of native spectrin and limited tryptic digest showed no difference between normals and HS patients. RBC separated into young and old fractions were used to examine the occurrence of protein aberrations associated with RBC age. Young RBC contained more G3PD (35%) and less protein 4.1 (6.5%) and actin (8.7%) than old. In male HS patients an increased G3PD content showed a linear correlation (p < 0.001) with a low concentration of blood haemoglobin. We conclude that aberrations of G3PD, and possibly protein 4.1, and actin, are associated with anaemia in HS. Increased anion-transporter or lowered protein 4.2 may be useful for diagnosis of HS, and were inherited in five out of six families where two generations were available. PMID- 8197408 TI - The need to integrate neuropsychological and experimental schizophrenia research. AB - Although the experimental and the neuropsychological approaches to the study of schizophrenic cognition have coexisted for many years, they remain detached, with virtually independent methods and literatures. The result has been a needless duplication of work and effort. In this article we review the emergence and representative research of each approach, examine model integrative studies, and suggest ways in which the two approaches can be better integrated to generate comprehensive cognitive schizophrenia theories and research. PMID- 8197409 TI - Neuropsychological risk indicators for schizophrenia: a review of family studies. AB - We reviewed potential neuropsychological risk indicators for schizophrenia by addressing two broad questions about neuropsychological performance in biological relatives of schizophrenia patients: (1) Is there evidence of deficits, and, if so, (2) are those deficits similar to deficits found in schizophrenia patients themselves? There has not yet been adequate validation of most neuropsychological risk indicators, but promising leads have emerged from studies of relatives of persons with schizophrenia. The strongest evidence of impairment in relatives was in sustained attention, perceptual-motor speed, and concept formation and abstraction; to a slightly lesser extent, mental control/encoding (primarily with distraction) was implicated as well. Impairments in verbal memory and verbal fluency were also found, although these have been less well studied. The pattern of deficits paralleled that found in schizophrenia patients, thus suggesting dysfunction in prefrontal, temporal-limbic, and attentional systems. Findings were similar for children and adult relatives of schizophrenia patients. It is suggested that future studies (1) emphasize comprehensive test batteries, (2) develop composite neuropsychological measures, (3) use profile and deviant responder analyses, (4) include psychiatric comparison groups, and (5) integrate neuropsychological assessments with brain imaging techniques. PMID- 8197410 TI - Psychometric high-risk paradigm, perceptual aberrations, and schizotypy: an update. AB - The psychometric high-risk strategy represents a useful methodologic adjunct to the traditional genetic high-risk research approach in the study of the etiology and development of schizophrenia. During the past 15 years, considerable research activity has focused on psychometrically identified individuals hypothesized to be en route to schizophrenia (i.e., putative schizotypes). The Perceptual Aberration Scale (PAS) has figured prominently in such prediction-oriented psychometric high-risk work. This report examines research using the PAS completed since 1987 that has established the instrument as a valid index for detecting liability for schizophrenia (or schizotypy) and as, arguably, the schizotypy index of choice for research. These results are presented and interpreted in light of Meehl's theoretical framework of schizotypy. Other measures of and assessment devices for schizotypy (schizophrenia-related liability) are identified. Of these other measures, the Chapmans' Magical Ideation Scale and the schizophrenia liability index of Moldin and colleagues are particularly well established. Methodologic suggestions for future psychometric high-risk and other work using objective measures of schizotypic psychopathology are offered. It is strongly recommended that future studies of schizotypy (or those in the planning stages, relying on psychometric detection methods use multiple psychometric indices to tap schizotypy or use a psychometric index in association with other promising biobehavioral markers of schizophrenia liability (e.g., sustained attentional deficits, eye movement dysfunction) for maximum efficiency in both location and definition of schizotypes. PMID- 8197411 TI - Family risk indicators in schizophrenia. AB - The literature is reviewed on three family risk indicators that have prognostic significance in schizophrenia: expressed emotion, affective style, and communication deviance, each measured in key relatives of schizophrenia patients. Expressed emotion and affective style have been used primarily to characterize family environments that predispose patients to psychotic relapses. Communication deviance has been used primarily to distinguish the communication styles of families of schizophrenia patients from those of families without schizophrenia. Data on the roles of genetic, biological, and psychosocial factors in the origins of these family attributes are reviewed. Although studies of family risk indicators have yielded relatively consistent cross-sectional and longitudinal findings, much remains to be clarified about what these constructs actually measure and their mechanisms of prediction. The implications of family risk research for prevention efforts are discussed. PMID- 8197412 TI - Single indicator of risk for schizophrenia: probable fact or likely myth? AB - The longitudinal followup strategy in high-risk research is being increasingly complemented by the use of psychosis-proneness scales to select subjects for study who might be vulnerable to schizophrenia and who show differences on laboratory measures that could act as endophenotypic markers for use in genetic investigations. Three types of experimental paradigm have been adopted, drawn from cognitive psychology, psychophysiology, and the neuropsychology of hemisphere function. Results adopting each of these approaches are examined, alongside recent factor-analytic evidence that psychosis-proneness scales currently in use tap up to four different components that map onto the clinical heterogeneity of schizophrenia (and possibly other forms of psychosis). No one of these components clearly emerges as, or points to, a single indicator of risk, though some aspect of neurocognitive functioning seems a likely candidate. Even so, it is argued, the clinical expression of vulnerability must be due to a convergence in an individual of several components of risk since individually (and notably so for "susceptibility to positive symptoms") they are very common in the healthy population. In evaluating the evidence, attention is drawn to two crucially different ways that investigators in schizophrenia research have construed the notion of continuity (1) as subclinical defect (or forme fruste of disease) having varying expression or (2) as biologically based personality dimensions that simultaneously describe the dispositions to aberrations of function leading to degree of illness. It is noted that the model of continuity chosen can significantly shape the way the results of risk research are interpreted and the theories of psychosis to which they give rise. PMID- 8197413 TI - Indicators of liability to schizophrenia: perspectives from genetic epidemiology. AB - Research in genetic epidemiology has provided powerful evidence that genetic factors contribute to the familial transmission of schizophrenia. However, the precise mode of inheritance has not been elucidated, and no disease susceptibility locus has been identified. Genetically complex illnesses such as schizophrenia can be characterized by multiple intermediate correlated traits or risk factors that likely play important roles in the susceptibility of individuals to developing the illness. Such biobehavioral traits potentially associated with liability to schizophrenia have been carefully studied by experimental psychopathologists and are discussed in this issue. This article discusses how correlated trait data collected from probands and their relatives can complement diagnostic assessments and offer promise for greatly enhancing the informativeness of pedigrees for genetic analysis and for facilitating replication of linkage findings. The results of analyses of simulated and real data discussed here suggest that assessment of biobehavioral traits with the greatest validity and cost-effectiveness should be required in the next generation of linkage and other genetic studies in schizophrenia. PMID- 8197414 TI - Stability of diagnosis: application to phenotype definition. AB - Using diagnostic stability data from independent diagnostic interviews conducted 6 years apart, we determine which diagnoses are predictive of diagnoses 6 years later. Logistic analysis using categorical predictors is used to establish ordinal relationships and to suggest diagnostic hierarchies. The multiple threshold multifactorial model is used to estimate the within-person correlation over time. Rather than use a simple dichotomy of "affected" or "unaffected," we provide odds ratios for mania, hypomania, and major depressive disorder in terms of diagnostic hierarchies, allowing a ranking of these diagnoses. This division increases the information for genetic studies or studies of a phenotype with correlated biological or environmental continuous covariates. The diagnosis of schizophrenia shows remarkable specificity across occasions. We find significant error in a cross-sectional assessment in this nonclinical sample. Assuming a multifactorial model, the proportion of variance in liability due to assessment error is approximately 30 percent under all schemes considered. The use of repeated measures in family studies is thus strongly recommended. PMID- 8197415 TI - Cognitive-perceptual, interpersonal, and disorganized features of schizotypal personality. AB - While two factors are currently thought to underlie individual differences in schizotypal personality, three factors may best explain schizotypal traits. This study used confirmatory factor analysis to assess five competing models of schizotypal personality in the general population: null model, one-factor model, simple two-factor model, Kendler two-factor model, and three-factor model. The computer program LISREL was used to analyze Schizotypal Personality Questionnaire subscale scores that reflect the nine traits of schizotypal personality. The scores were obtained from (1) a sample of 822 undergraduates and (2) a replication sample of 102 subjects drawn from the community. Results indicate replicable support for a three-factor model reflecting cognitive-perceptual, interpersonal, and disorganized latent factors. Low intercorrelations between the first two factors and the lack of fit by a one-factor model are partially inconsistent with recent notions that a single vulnerability dimension underlies schizotypal personality. It is argued that future investigations should assess the correlates of all three schizotypal factors in clinical and nonclinical samples in addition to the two more traditional factors. It is hypothesized that three factors of schizophrenic symptomatology observed in recent studies may reflect an exaggeration of three analogous factors found in the general population. PMID- 8197416 TI - Can estradiol modulate schizophrenic symptomatology? AB - Using epidemiologic data, in an earlier study we formulated the hypothesis that estrogens can delay the onset of schizophrenia in females by raising the vulnerability threshold for this disease. In animal experiments, Hafner and colleagues found evidence that chronic estradiol treatment reduces the sensitivity of dopamine (D2) receptors in the brain. In the clinical study presented in this article, as a further step we examined the antipsychotic properties of estradiol in human females by testing whether schizophrenic symptomatology varies with estradiol serum levels throughout the menstrual cycle. We examined 32 acutely admitted female schizophrenia patients (Present State Examination/CATEGO diagnosis, ICD-9) with a history of regular menstrual cycles, ages 18 to 43 (mean = 30.5), during their hospital stays (3-8 weeks), analyzing hormonal parameters and applying various rating scales for psychopathology every 7 days. In all patients, estradiol serum levels were markedly reduced as compared with the normal population, and fluctuations throughout the cycle were dampened. Nevertheless, a significant association emerged between estradiol levels, on the one hand, and psychopathology scores, on the other--that is, the psychiatric symptomatology as assessed by the clinical psychiatrist (Brief Psychiatric Rating Scale, p < or = 0.01), behavior on the ward as assessed by the nursing staff (Nurses' Observation Scale for Inpatient Evaluation p < or = 0.01), paranoid tendencies and general well-being as assessed by the patients themselves (Paranoid-Depressivitats-Skala paranoid score p < or = 0.05; Befindlichkeits Skala p < or = 0.05). Psychopathology seems to improve when estradiol levels rise, and vice versa. These findings can be interpreted as further evidence for a protective effect of estrogens in schizophrenia, possibly due to the known anti dopaminergic activities of these hormones. PMID- 8197417 TI - First person account: life with a mentally ill spouse. PMID- 8197418 TI - Clozapine: benefits and risks. PMID- 8197419 TI - Measuring liability to schizophrenia: progress report 1994: editors' introduction. AB - The first aim of this issue of the Schizophrenia Bulletin is to provide an up-to date review of the major domains of research in the experimental psychopathology of schizophrenia, in which important contributions to our understanding of putative pathophysiologic mechanisms have been made. This research has identified several biobehavioral traits as measures of enhanced liability to schizophrenia. Rather than present a substantive review of the research on a particular trait, the authors of several articles focus on a critical appraisal and evaluation of the literature since 1987 in their particular area. The second aim of this issue is to present new methodologic approaches and conceptualizations for incorporating biobehavioral trait data in future psychiatric research designs. Now is the time not only to recognize past contributions but also to recognize that further advances in our understanding of the etiology and pathophysiology of schizophrenia may depend on continued research in experimental psychopathology that culminates in an integration in both methods and research design across disparate scientific fields. PMID- 8197420 TI - Impaired attention, genetics, and the pathophysiology of schizophrenia. AB - Impaired attention is commonly observed among schizophrenia patients and those at genetic risk for the disease. This article reviews over 40 studies that used various versions of the Continuous Performance Test (CPT) as the primary measure of attention. These studies of normal subjects, affected patients, and various at risk populations demonstrate that the CPT is a psychometrically sound procedure that consistently discriminates affected patients from controls. Sufficiently difficult versions of this task have also demonstrated that impaired attention is (1) evident in schizophrenia patients regardless of clinical state, (2) detectable before illness onset, (3) apparently heritable, (4) specific--in terms of distinct profile patterns--to schizophrenia, and (5) predictive of later behavioral disturbances in susceptible individuals. Selected studies are also discussed that examine the role of attentional deficit in the pathophysiology of schizophrenia and its potential consequences for personality development. With respect to pathophysiology, preliminary data suggest that subcortical brain dysfunction has an important role in the attentional deficits tapped by the CPT. With respect to personality, an association between chronically impaired attention and deficient social skills has been found. It is concluded that the CPT is a cost-effective measure of the attentional deficit commonly found in affected schizophrenia subjects and those at risk for the disorder, and is therefore a potentially valuable screening device for preventive intervention programs. PMID- 8197421 TI - Eye tracking and schizophrenia: a selective review. AB - The replications of the finding of eye tracking dysfunction (ETD) in schizophrenia patients and their first-degree relatives suggest that ETD may be informative in studies of a schizophrenia genotype having broadly defined phenotypes. We review and critically assess the literature on ETD with respect to syndrome and familial specificity and discuss the quantitative assessment of eye tracking. PMID- 8197422 TI - Event-related potentials (ERPs) as indicators of risk for schizophrenia. AB - Evidence is reviewed concerning the viability of cognitive event-related potential (ERP) indices to serve as psychophysiological markers for liability to schizophrenia and schizophrenia-related disorders. Methodologic problems that hinder the establishment of ERPs as such markers are also detailed. The ERP data from prospective high-risk and family-transmission paradigms were subjected to criteria that have been used to establish the marker status of a psychobiological variable. It is concluded that (1) there is a clear need for more studies of ERP component stability and of transmission of ERP parameters within normal families; (2) multiple tasks (in addition to the oddball experiment) must be used to probe the range of information-processing deficits in the schizophrenic syndrome; (3) investigators should pay greater attention to the scalp distribution of ERP components; and (4) profiles of multiple ERP indices may be required to enhance the probability of achieving diagnostic specificity. PMID- 8197423 TI - Structural brain abnormalities as indicators of vulnerability to schizophrenia. AB - The literature on structural brain abnormalities in schizophrenia is examined to determine whether these abnormalities represent viable candidate markers of vulnerability to the disorder. A majority of studies agree in finding that schizophrenia patients as a group have significantly larger ventricles and smaller limbic brain structures than normal control subjects, but about 50 percent of patients fall within the range of control subjects on these measures. This result has been interpreted to suggest that structural abnormalities characterize only a subgroup of patients. However, given the substantial degree of normal variability in brain structure between families, the use of biologically unrelated individuals as controls is misleading. Studies that have compared schizophrenia patients with their unaffected first-degree relatives have found a much higher sensitivity rate for ventricular enlargement and reduced limbic volumes (i.e., 70%-100%). This high within-family sensitivity, together with evidence from meta-analytic reviews of a substantial relationship between ventricular enlargement and severity of illness, argues in favor of a continuous distribution of the brain pathology in schizophrenia and against a model in which the pathology characterizes only a subgroup of patients. The structural abnormalities observed in both younger and older patients have been found to be highly correlated with familial risk for schizophrenia and obstetric complications, suggesting that some part of the deviance may be present in the premorbid state and that it may reflect both genetic and environmental etiologic processes. The evidence for specificity of the deficits to schizophrenia is equivocal, but no study has yet compared the within-family sensitivities of morphological measures among the major psychiatric conditions. Additional studies using first-degree relatives and well-defined neuroanatomical measurements are needed to determine which brain regions have the highest sensitivities as indicators of schizophrenia in families. PMID- 8197424 TI - Thoracoscopic pleurodesis. AB - Thoracoscopic pleurodesis for pneumothorax was performed on 23 patients (16 men, 7 women), including seven with chronic obstructive pulmonary disease, over a 12 month period. Single-lumen intubation with spontaneous ventilation were used making intrapleural insufflation unnecessary. Postoperatively the patients required chest drainage for 1-28 (mean 3) days and remained in hospital for 3-33 (mean 6) days. The 14 gainfully employed patients had 11-40 (mean 20) days' sick leave. Hydrothorax requiring pleurocentesis developed in one patient after thoracoscopy. Pneumothorax recurred in another immediately after removal of the chest drain, but resolved definitively after 2 more days of drainage. A patient with obstructive lung disease required ventilator management for a week after the operation, but otherwise no serious complications were observed. PMID- 8197425 TI - Less than lobar resections for bronchogenic carcinoma. AB - We performed less than lobar resections for peripheral clinical Stage I primary lung cancers on 170 patients treated between 1973 and 1987 at two university centers, one in Hawaii and one in Israel. Most patients were poor risks and several had FEV1 < 1 liter. There were 6 (3.5%) hospital deaths. There were 58 segmental resections, 97 wedge resections and 15 less than lobar resections not otherwise specified. Seventy-three patients (43%) are living free of cancer from 5 to 11 years postoperatively and 20 additional patients died of causes unrelated to lung cancer after 5 years; thus disease free five year survival was 54.7%. Patients with adenocarcinoma had poorer prognosis than other cell types. Twenty three patients (13.5%) had synchronous or metachronous second primary lung cancers. Nine of these patients are long term survivors. Twenty-four patients (14.1%) developed local recurrences with or without distant metastases. This promising long term cancer-free survival and the frequency of second primary lung cancers justifies less than lobar resection for peripheral, Stage I bronchogenic carcinoma, especially in the poor risk patient. PMID- 8197426 TI - Relationships between divisions of the middle bronchus and vascularization patterns in the middle lung lobe. AB - In 100 right human lungs the main bronchus, the pulmonary artery and the pulmonary vein were injected with 65% methyl methacrylate and then digested in sulphuric acid. The resulting specimens were studied to observe the divisions of the middle lobe bronchus and the types of arterial and venous vascularization of this lobe. The lobe was always entered by one lobar bronchus, which usually divided into two segmental bronchi. In 53% of the middle lobes with this bronchial pattern there was one artery. When the lobar bronchus divided into three branches, at least two arteries entered the lobe in almost all cases. Complete consistency between the pattern of bronchial division and that of arterial vascularization of the middle lobe was found in almost two-thirds of cases. Associations between patterns of bronchial division and of venous drainage from the middle lobe were found in slightly more than half of the cases. PMID- 8197427 TI - Chondrosarcoma of the thoracic wall. AB - Eight cases of chondrosarcoma of the thoracic wall were treated during a 13-year period. The radicality of tumor resection was positively correlated with patient survival. Wide primary resection without preceding biopsy is advocated for thoracic lesions suspected from computed tomography and magnetic resonance imaging to be chondrosarcoma. PMID- 8197428 TI - Osteosynthesis of the injured chest wall. Use of the AO (Arbeitsgemeinschaft fur Osteosynthese) technique. AB - Open reduction and osteosynthesis with AO (Arbeitsgemeinschaft fur Osteosynthese) technique, using 3.5 mm reconstruction plates and 3.5 mm cancellous screws, were performed in all cases of chest wall injury considered for surgical stabilization since 1990, viz. 11 with posttraumatic flail chest and one with painful nonunion of two ribs. In the ten survivors with flail chest, stability was achieved without secondary dislocation, giving good pain relief, improved respiratory mechanics and reduced duration of ventilatory support and intensive care requirements. Lasting pain relief was obtained also in the case of costal nonunion. No complications related to the osteosynthesis arose during follow-up for a mean of 11 months. Chest wall injuries in flail chest and painful nonunion of ribs can be easily and efficiently stabilized with the AO technique. PMID- 8197429 TI - Conduction disturbances after blood and crystalloid cardioplegia in coronary bypass surgery. AB - Postoperative conduction disturbances after coronary artery bypass grafting were analyzed in 100 patients who randomly received either blood or crystalloid cardioplegia. Conduction disturbances, mostly transient, developed after termination of cardiopulmonary bypass in 30 of the 100 patients--15 in either group. Ischaemia appeared to be a major determinant for conduction disturbances. Previous inferior myocardial infarction and stenosis of the right coronary artery both exposed the patient to risk of right bundle branch block. PMID- 8197430 TI - Surgery for chronic left ventricular aneurysm. Benefits and side effects. AB - Seventy patients who underwent elective resection of symptomatic postinfarction apico-anterior left ventricular (LV) aneurysm with or without coronary revascularization are reviewed. The early (< or = 30 day) mortality was 5.7%. Mural thrombosis occurred in 29 cases (41.4%), unrelated to the degree of preoperative LV impairment and predictable from preoperative LV angiography in only seven cases. The response to surgery comprised significant overall improvement of global LV ejection fraction (LVEF) during rest and of all variables in stress testing. This LVEF recovery correlated significantly with that of peak ejections rate, a variable of myocardial contractility. Contrastingly, right ventricular ejection fraction (RVEF) at rest decreased slightly but significantly without correlation to preoperative RVEF or LVEF. In comparisons between patients with congestive heart failure or angina at rest as dominant symptom, the former group showed greater depression of preoperative watt and LVEF but better postoperative recovery of these variables, while right ventricular deterioration was significant only in the latter. Postoperative recovery was best in patients with poor preoperative LV function (LVEF < or = 20%), even when surgery comprised only aneurysmectomy in isolated but ungraftable LAD disease (5 cases). The observed RV deterioration may be 'nonspecific', but it must be kept in mind as a side effect of the operation, as it detracts unpredictably from postoperative ventricular recovery. Patients with well preserved preoperative LVEF, small LV aneurysm and marginal expected post aneurysmectomy changes according to LaPlace's law are probably at risk, and surgery should then instead be directed towards preserving the remaining viable myocardium by direct revascularization. PMID- 8197431 TI - Papillary carcinoma in a huge intrathoracic goiter with tracheal stenosis and invasion. Case report. AB - A rare case in tracheal invasion by a papillary carcinoma in an intrathoracic goiter is reported. Subtotal thyroidectomy and tracheoplasty were performed. Surgery should be considered as first-line treatment of intrathoracic goiter in order to avoid future compression of the respiratory tract and to remove possible concomitant malignant lesion. PMID- 8197432 TI - Primary osteogenic sarcoma of the posterior mediastinum. Case report. AB - Extraosseous osteogenic sarcoma of the mediastinum is an extremely rare tumour, usually arising in the anterosuperior compartment. Clinical findings in the first reported case of high-grade osteogenic sarcoma arising in the posterior mediastinum are described. PMID- 8197433 TI - Thoracic duct cyst of the mediastinum. Case report. AB - A mediastinal thoracic duct cyst was incidentally found in an asymptomatic 45 year-old man. The cyst, 6 cm in diameter, was soft and unilocular, with an extremely thin wall, and contained chyle. It was successfully excised. PMID- 8197435 TI - Late postoperative cardiac tamponade presenting as a pulsatile epigastric mass. Case report. PMID- 8197434 TI - Management of postpneumonectomy syndrome by intrapleural injection of sulfur hexafluoride. Case report. AB - Left postpneumonectomy syndrome was managed by injection of sulfur hexafluoride (SF6) into the pleural space. This measure permitted irradiation of a contralateral, second primary lung cancer without resulting pulmonary fibrosis. Such use of SF6 may be an option for prophylaxis against postpneumonectomy syndrome. PMID- 8197436 TI - Fracture of a composite aortic graft. Case report. AB - Fracture of a valved composite graft was found 3 years after its implantation in the ascending aorta. This appears to be the first reported case of such fracture. PMID- 8197437 TI - Successful resection of descending thoracic aortic aneurysm using hypothermic total body retrograde perfusion without aortic clamp. Case report. AB - A descending thoracic aortic aneurysm was safely resected via a median sternotomy, using total body retrograde perfusion without an aortic clamp. This new technique is an excellent adjunct in surgery for aneurysm of the proximal descending thoracic aorta. PMID- 8197438 TI - What's bred in the bone. PMID- 8197439 TI - Lollipop, lollipop. A candied sedative with a kick arouses opposition from doctors. PMID- 8197440 TI - Endangered support of basic science. PMID- 8197441 TI - Neural eavesdropping. PMID- 8197442 TI - Take the pain? Lidocaine comes under suspicion as a carcinogen. PMID- 8197443 TI - Family matters. Revised dates invigorate debate on human origins. PMID- 8197444 TI - Evidence for a biological influence in male homosexuality. PMID- 8197445 TI - The biological evidence challenged. PMID- 8197446 TI - How interferons fight disease. PMID- 8197447 TI - East side story: the origin of humankind. PMID- 8197448 TI - Blood type and the risk of gastric disease. PMID- 8197449 TI - 1996 U.S. science policy. Memo backs basic research with words, not cash. PMID- 8197450 TI - Drug discovery on the assembly line. PMID- 8197451 TI - Cemetery reveals complex aboriginal society. PMID- 8197452 TI - Genome mapping. Closing in on human and mouse maps. PMID- 8197453 TI - Mystery ailment strikes Serengeti lions. PMID- 8197454 TI - A biochemical function for ras--at last. PMID- 8197455 TI - Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. AB - Through the study of transcriptional activation in response to interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma), a previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that then phosphorylate substrate proteins called STATs (signal transducers and activators of transcription). The phosphorylated STAT proteins move to the nucleus, bind specific DNA elements, and direct transcription. Recognition of the molecules involved in the IFN-alpha and IFN-gamma pathway has led to discoveries that a number of STAT family members exist and that other polypeptide ligands also use the Jak-STAT molecules in signal transduction. PMID- 8197456 TI - Structure of the allosteric regulatory enzyme of purine biosynthesis. AB - Multi-wavelength anomalous diffraction (MAD) has been used to determine the structure of the regulatory enzyme of de novo synthesis of purine nucleotides, glutamine 5-phosphoribosyl-1-pyrophosphate (PRPP) amidotransferase, from Bacillus subtilis. This allosteric enzyme, a 200-kilodalton tetramer, is subject to end product regulation by purine nucleotides. The metalloenzyme from B. subtilis is a paradigm for the higher eukaryotic enzymes, which have been refractory to isolation in stable form. The two folding domains of the polypeptide are correlated with functional domains for glutamine binding and for transfer of ammonia to the substrate PRPP. Eight molecules of the feedback inhibitor adenosine monophosphate (AMP) are bound to the tetrameric enzyme in two types of binding sites: the PRPP catalytic site of each subunit and an unusual regulatory site that is immediately adjacent to each active site but is between subunits. An oxygen-sensitive [4Fe-4S] cluster in each subunit is proposed to regulate protein turnover in vivo and is distant from the catalytic site. Oxygen sensitivity of the cluster is diminished by AMP, which blocks a channel through the protein to the cluster. The structure is representative of both glutamine amidotransferases and phosphoribosyltransferases. PMID- 8197457 TI - A protein phosphatase 2C involved in ABA signal transduction in Arabidopsis thaliana. AB - The plant hormone abscisic acid (ABA) mediates various responses such as stomatal closure, the maintenance of seed dormancy, and the inhibition of plant growth. All three responses are affected in the ABA-insensitive mutant abi1 of Arabidopsis thaliana, suggesting that an early step in the signaling of ABA is controlled by the ABI1 locus. The ABI1 gene was cloned by chromosome walking, and a missense mutation was identified in the structural gene of the abi1 mutant. The ABI1 gene encodes a protein with high similarity to protein serine or threonine phosphatases of type 2C with the novel feature of a putative Ca2+ binding site. Thus, the control of the phosphorylation state of cell signaling components by the ABI1 product could mediate pleiotropic hormone responses. PMID- 8197458 TI - Estrogen receptor-associated proteins: possible mediators of hormone-induced transcription. AB - The estrogen receptor is a transcription factor which, when bound to estradiol, binds DNA and regulates expression of estrogen-responsive genes. A 160-kilodalton estrogen receptor-associated protein, ERAP160, was identified that exhibits estradiol-dependent binding to the receptor. Mutational analysis of the receptor shows that its ability to activate transcription parallels its ability to bind ERAP160. Antiestrogens are unable to promote ERAP160 binding and can block the estrogen-dependent interaction of the receptor and ERAP160 in a dose-dependent manner. This evidence suggests that ERAP160 may mediate estradiol-dependent transcriptional activation by the estrogen receptor. Furthermore, the ability of antiestrogens to block estrogen receptor-ERAP160 complex formation could account for their therapeutic effects in breast cancer. PMID- 8197459 TI - Tetrad analysis possible in Arabidopsis with mutation of the QUARTET (QRT) genes. AB - Two Arabidopsis thaliana genes, QRT1 and QRT2, are required for pollen separation during normal development. In qrt mutants, the outer walls of the four meiotic products of the pollen mother cell are fused, and pollen grains are released in tetrads. Pollen is viable and fertile, and the cytoplasmic pollen contents are discrete. Pollination with a single tetrad usually yields four seeds, and genetic analysis confirmed that marker loci segregate in a 2:2 ratio within these tetrads. These mutations allow tetrad analysis to be performed in Arabidopsis and define steps in pollen cell wall development. PMID- 8197460 TI - Liquid-crystalline mesophases of plasmid DNA in bacteria. AB - Bacterial plasmids may often reach a copy number larger than 1000 per cell, corresponding to a total amount of DNA that may exceed the amount of DNA within the bacterial chromosome. This observation highlights the problem of cellular accommodation of large amounts of closed-circular nucleic acids, whose interwound conformation offers negligible DNA compaction. As determined by x-ray scattering experiments conducted on intact bacteria, supercoiled plasmids segregate within the cells into dense clusters characterized by a long-range order. In vitro studies performed at physiological DNA concentrations indicated that interwound DNA spontaneously forms liquid crystalline phases whose macroscopic structural properties are determined by the features of the molecular supercoiling. Because these features respond to cellular factors, DNA supercoiling may provide a sensitive regulatory link between cellular parameters and the packaging modes of interwound DNA in vivo. PMID- 8197461 TI - Reversal of terminal differentiation mediated by p107 in Rb-/- muscle cells. AB - The terminal differentiation of mammalian muscle cells requires the tumor suppressor retinoblastoma protein (Rb). Unlike their wild-type counterparts, multinucleated myotubes from mouse cells deficient in Rb (Rb-/-) were induced by serum to re-enter the cell cycle. Development of the myogenic phenotype in Rb-/- cells correlated with increased expression of p107, which interacted with myogenic transcription factors. Serum-induced cell cycle reentry, on the other hand, correlated with decreased p107 expression. Thus, although p107 could substitute for Rb as a cofactor for differentiation, it could not maintain the terminally differentiated state in Rb-/- myotubes. PMID- 8197462 TI - [What is the value of score systems?]. AB - Numerous scoring systems are available for various particular situations. Some clinicians consider scores as mandatory for daily clinical decision making, while others see them only as additional work with no proven benefit except for scientific aspects. Although scoring systems have their limitations, they can also be of value. This article provides an overview of existing systems used in emergency and intensive care medicine. The specific aims of different scoring systems are discussed and evaluated for the areas of disease classification, monitoring of individual patients and applications to individual decisions, quality assurance (comparison of patient groups and therapies), economic evaluation and global triage decisions. Despite the additional workload it is concluded that scoring systems are of proven benefit for classification of the degree of severity of a disease process, quality assurance, and better assessment of costs containment. These instruments will become increasingly important in our current discussion on changes in health care systems. PMID- 8197463 TI - [Comparison of various trauma score systems. An overview]. AB - Among the more than 50 scoring systems available for quantitative evaluation of injury severity, only a few have proved effective in clinical practice. In particular, the Revised Trauma Score (RTS), referring to physiological variables, has proved effective in preclinical use and otherwise, the Injury Severity Score (ISS), referring to anatomical data. There is a tendency in the development of new scoring systems to aim at higher predictive accuracy, forfeiting practicability. The initial purpose of scoring--an early assessment of the risks- is being pushed into the background. The TRISS method, which includes the RTS, ISS, patient's age, and mechanism of injury, is regarded as the international standard. However, it has the disadvantage of a low sensitivity of 60% for blunt trauma, resulting in a high rate of unexpected deaths. Reasons for this are underestimation of head injuries, multiple injuries to one body region, and failure to take full account of the individual patient's age. The new ASCOT method, in which the ISS is replaced by the Anatomic Profile, and the age of the patient is given more consideration, hardly brings better results--in spite of quite time-consuming methods. When the scoring systems currently available are applied their specific deficiencies and limited evidence must be borne in mind. Nevertheless, they are an important scientific instrument for comparative examinations, and indispensable for quality assurance and economic analyses. To improve the predictive accuracy, biochemical parameters and chronic diseases should be considered, in addition to existing scores. PMID- 8197464 TI - [Practical and theoretical limits of score systems]. AB - Trauma-scoring is a measurement of injury severity. Before conclusions can be drawn from their results, their validity, reliability and practicability need to be known. With respect to these factors the following statements may be proposed: some scores do have relatively low inter-rater reliability; retrospective interpretation of findings and diagnoses in the patient records may be equivocal; parameters contributing to the score may be lacking in some records; scoring may be time-consuming; the parameters selected to make up the score may not include all the relevant ones; the influence of time is neglected; different methods of patient selection may confound the interpretation of scoring results; most scores are only evaluated with respect to mortality; the scores are interpreted exclusively on the basis of statistical probabilities. We suggest that such scores as the ISS, PTS, (R)TS, which have been fairly well studied with respect to validity, reliability, and practicability, be prepared. PMID- 8197465 TI - [Quality assurance in the management of severely ill patients: how can score systems help?]. AB - Quality control requires the definition of a quality standard, followed by quality documentation and comparison. In the case of deviation from the standard, the first step in quality assurance is the search for the reasons. After identification of weak points, strategies for quality improvement must then be developed and implemented. With prehospital trauma care as an example, a practical model of quality assurance is presented. Data analysis was performed using the prospective database of 8792 trauma patients who received prehospital trauma care in Cologne from 1. 1. 87 to 31. 12. 90. The Trauma Score was used for classification of the severity of injury. The quality standard in prehospital treatment of severely injured patients is defined as institution of an intravenous line, early intubation and transportation to a trauma centre. The time at the scene of the accident should not exceed 31 min. Among the 8792 trauma patients, 834 had severe injuries, defined as a Trauma Score equal to or less than 12 or a Glasgow Coma Scale equal to or less than 7. An intravenous line was started in 91.6%, early intubation was performed in 82.7%, and transportation to a trauma centre was realized in 62.5% of the patients. The average time at the scene was 34 min. Obviously the standard was not always achieved. Reasons for deviation from the standard are discussed. The fascinating aspect of the model proposed is that it enables quality assurance of prehospital treatment without recourse to hospital data. PMID- 8197466 TI - Outcome prediction for the individual patient in the ICU. AB - A very difficult clinical problem facing surgeons is knowing when further treatment is futile and no longer appropriate in a patient who has developed severe complications after surgery and is being treated in an intensive care unit. It is now possible to prolong the process of dying among such patients. This results in unnecessary pain and loss of dignity for the patient, anguish and distress for the patient's relatives and is dehumanizing for the clinical and nursing staff. It has also tremendous implications in the use of limited health care resources. A computer model designed to aid this process has to have the following properties: it must reflect the dynamic pathophysiological process and be able to predict death with extreme accuracy and early in the clinical course. The Riyadh algorithm uses computerised dynamic trend analysis of daily organ failure scores (APACHE II score corrected for the number and duration of organ failures), noting the rate of change in score relative to that of the previous day and an absolute threshold to predict death has been developed for this purpose. The algorithm was developed by tracking the daily scores of 200 IUC patients until their death or discharge from the intensive care unit. It was subsequently validated perspectively on 831 patients. During the validation process, the clinicians were blinded to the predictions. There wer 290 deaths and the program predicted 109 deaths (38% of all deaths) with no false-positive predictions. Forty percent of the predictions were made within 48 h in the ICU and 74% within a week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8197467 TI - [Follow-up of severely injured patients with scoring systems on the intensive care unit]. AB - A variety of different scoring systems are in current use, with an increasing impact on intensive care treatment. Originally these scoring systems were applied to evaluate objective grading and to estimate survival and mortality. More recently, other potential applications have been investigated. While clinical monitoring and assessment of therapeutic success are the primary goals, scoring systems can be used to define comparable patient collectives and to delineate predefined patient groups for clinical trials. Scoring systems are gaining increasing importance in evaluation of the level of therapeutic intervention and care provided as well as in quality assessment. On the whole, however, accuracy, the probability that outcome will be correctly predicted for an individual patient, is still inadequate. Although desirable, individual patient prediction is therefore not allowed, and therapeutic strategies and therapy evaluation based on scoring systems cannot be implemented, or only in a limited way. For daily use in individual patient evaluation--monitoring, therapy response, prognosis- biochemical monitoring is still of primary importance. Scoring systems have now found a useful application as a supplement, rather than a rival, to clinical patient evaluation. PMID- 8197468 TI - [Scores as decision aids]. AB - Scoring systems are nowadays said to be helpful in decision-making in preclinical and early clinical treatment of multiple trauma patients. To evaluate the importance of these scores in daily routine, we analysed the scores routinely used in our department at the Hannover Medical School. We present three scoring systems: the Polytrauma Score, the Pelvis Score, and the Hannover Fracture Scale. All of these have certain qualities relevant to the aspects of decision-making and prognostic value. The evaluation demonstrates that these scoring systems are genuinely helpful, especially for the inexperienced. PMID- 8197469 TI - [Follow-up of spinal injuries with transverse spinal cord lesion]. AB - There are several scores available for assessment of disability and handicap in rehabilitation. In primary treatment most interest has so far been given to the assessment of neurological recovery after operative decompression of the spinal cord. Comparison of the results obtained with this method and the outcome in patient groups treated conservatively revealed no quantitative differences. However, the quality of results was found to be better after surgery, particularly in the functional outcome. Scores should take account of this. The neurological classification of ASIA, IMSOP and DMGP seems to be suitable for assessment of the course through-out the rehabilitation period. PMID- 8197470 TI - [Instruments for measuring the quality of life of severely injured patients]. AB - Trauma can be defined as either a somatic injury or a psychological reaction in the person affected. The emotional disturbances and psychosocial problems of trauma patients in particular, though still measurable a year or even longer after the event, have rarely been taken into account in surgical studies. Quality of life is a relevant endpoint in multiple trauma patients, insofar as rehabilitation seems to be complicated by non-efficient psychological coping. With reference to the prerequisites for a scientifically sound measuring method four instruments are described that seem to be suitable for measuring quality of life in multiple trauma patients. In addition, practical advice is given for the design of longitudinal studies focused on quality of life in trauma patients. PMID- 8197471 TI - [Trauma register of the German Society of Trauma Surgery. "Scoring" study committee of the German Society of Trauma Surgery]. AB - In January 1992 the German Society of Trauma Surgery founded the working group "Scoring" with the aim of developing guidelines for a standardized use of scoring systems in severely injured patients. The study group developed the "Trauma Register" for prospective data collection in severely injured patients, from the scene of the accident up to discharge from hospital. The register contains routinely available anatomical and physiological variables, diagnostic and therapeutic interventions, and any complications. Calculation of different scores is possible from the data collected. The completed registers will be collected and processed together. Statistical analyses are possible for the total population as well as for single trauma centres. The aim of the Trauma Register is the definition of standards on diagnostic and therapeutic concepts and the evaluation of trauma care. Trauma centres can compare their own performance against given standards (quality control). If there are deviations from the norms the reasons have to be identified and necessary countermeasures should be implemented (quality assurance). The register has been tested in a feasibility phase in six German trauma centres and will hopefully have an impact comparable to that of the Major Trauma Outcome Study (MTOS) in the USA. PMID- 8197472 TI - Radiation hybrids for the proximal long arm of the X chromosome and their use in the derivation of an ordered set of cosmid markers from a defined subregion in proximal Xq13.1. AB - We have defined a radiation hybrid panel for Xq11-q22 characterized with 20 DNA markers and shown how the panel can be used in conjunction with Alu-PCR and a gridded X-specific cosmid library to isolate cosmids from a preselected subregion. We used Alu-PCR products derived from two radiation hybrids, IHB2-B30 and IHB1-A12, sharing a segment in proximal Xq13.1, containing DXS453 to CCG1, as the only human component in common. Used as probes, these Alu-PCR products identified 39 cosmids on the gridded X-cosmid libraries that were positive for both probes. The target specificity of the derived cosmids was very high, 11 of 13 cosmids tested mapped to the region of fragment overlap in the hybrids, as was determined by two translocation breakpoints bordering most of the target interval. Accounting for a redundancy of four in the libraries, the isolated 39 cosmids should correspond to about 10 independent loci derived from the region of fragment overlap defined by these radiation hybrids. In addition, a subset of five radiation hybrids having breakpoints in the target region could be used to further subdivide the 11 cosmids into an ordered set of five submapping intervals of Xq13.1. PMID- 8197473 TI - Spontaneous and induced homologous recombination between lacZ chromosomal direct repeats in CV-1 cells. AB - A lacZ substrate for intrachromosomal homologous recombination was generated at a specific site within the genome of CV-1 cells by FLP recombinase-mediated gene targeting. A histochemical stain was used to detect cells that contained recombined lacZ genes. The spontaneous rate of homologous recombination was approximately 1 x 10(-5) events per cell generation. Recombination was induced 30 fold in cells following exposure to mitomycin C (MMC) and by serum starvation. These results demonstrate the utility of the FLP recombinase in modifying the genome of mammalian cells in a predetermined manner and show that homologous recombination between direct repeats is increased in cells as a result of the withdrawal of serum growth factors. PMID- 8197474 TI - Structure and expression of the Huntington's disease gene: evidence against simple inactivation due to an expanded CAG repeat. AB - Huntington's disease, a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expanded, unstable trinucleotide repeat in a novel 4p16.3 gene. To lay the foundation for exploring the pathogenic mechanism in HD, we have determined the structure of the disease gene and examined its expression. The HD locus spans 180 kb and consists of 67 exons ranging in size from 48 bp to 341 bp with an average of 138 bp. Scanning of the HD transcript failed to reveal any additional sequence alterations characteristic of HD chromosomes. A codon loss polymorphism in linkage disequilibrium with the disorder revealed that both normal and HD alleles are represented in the mRNA population in HD heterozygotes, indicating that the defect does not eliminate transcription. The gene is ubiquitously expressed as two alternatively polyadenylated forms displaying different relative abundance in various fetal and adult tissues, suggesting the operation of interacting factors in determining specificity of cell loss. The HD gene was disrupted in a female carrying a balanced translocation with a breakpoint between exons 40 and 41. The absence of any abnormal phenotype in this individual argues against simple inactivation of the gene as the mechanism by which the expanded trinucleotide repeat causes HD. Taken together, these observations suggest that the dominant HD mutation either confers a new property on the mRNA or, more likely, alters an interaction at the protein level. PMID- 8197475 TI - Detection of deletion mutations extending beyond the HPRT gene by multiplex PCR analysis. AB - A multiplex PCR assay was developed for the rapid analysis of deletion size at the hypoxanthine phosphoribosyltransferase (hprt) locus. The DNA sequence of mapped DNA segments flanking the hprt gene was determined. These cloned DNAs were derived from the ends of a set of overlapping yeast artificial chromosomes (YAC) defining a contig of 8 Mb at Xq26 and including hprt. We used "bubble" PCR to isolate an additional YAC end-clone. Seven primer pairs were derived from DNA sequence analysis of the clones and incorporated into a multiplex PCR assay. These primer pairs define loci located approximately 750 kb and 350 kb upstream of hprt and 300 kb, 540 kb, 900 kb, 1260 kb, and 1400 kb downstream of hprt. A primer pair for an unlinked and unselected gene sequence (K-ras) was also included in the multiplex reaction to serve as an internal positive control. Using this new assay, hprt mutant DNAs can be screened to determine the extent of deletion. Deletions larger than 2 Mb have been identified and show that large deletions can be tolerated at this hemizygous locus. PMID- 8197476 TI - The receptor-recycling and lysosome biogenesis mutant TfT1.11 belongs to a new complementation group, End6. AB - We have previously isolated a Chinese hamster ovary (CHO) mutant with a temperature-dependent pleiotropic defect in receptor recycling. This mutant, TfT1.11, has also been shown to have defects in fluid-phase endocytosis and lysosome biogenesis. Previously isolated CHO cell mutants with defects in endocytosis have been assigned to five recessive complementation groups (End1 End5). We have performed complementation analysis using polyethylene glycol induced fusion of genetically marked sublines of TfT1.11 with representative mutants from each of the End groups. Complementation of the receptor trapping and lysosome biogenesis defects as well as temperature lethality was observed with all groups, demonstrating that TfT1.11 defines a new complementation group, End6. PMID- 8197477 TI - Generation of a mouse model for citrullinemia by targeted disruption of the argininosuccinate synthetase gene. AB - Argininosuccinate synthetase (ASS) is a urea cycle enzyme that forms argininosuccinate from citrulline and aspartate. Mutations at the ASS locus in man cause the inherited disease, citrullinemia. Citrullinemia is inherited as an autosomal recessive trait and is characterized, biochemically, by elevated levels of blood citrulline and ammonia and often results in early neonatal death if untreated. We have used homologous recombination in embryonic stem cells to generate a line of mice having a targeted disruption of the Ass gene. Homozygous mutant animals develop high levels of blood citrulline, become hyperammonemic, and die within one or two days after birth. Because the phenotype of the mutant mice closely resembles that of humans who lack the ASS enzyme, we expect that these mice will serve as a useful model for exploring new treatments for citrullinemia including somatic gene therapy. PMID- 8197478 TI - Inclusion of synthetic DNA templates of similar length and base composition to PCR-amplified products in restriction enzyme digestions: an efficient aid in characterization of point mutations. AB - Because of a subtle anomaly we encountered upon an analytical gel while characterizing a point mutation in an exon of a patient, we decided to perform expensive and time-consuming procedures to characterize the anomaly. Although initial and subsequent Southern blots and PCR analyses of this patient's mutation suggested that his mutation lay directly within a TaqI recognition site, further characterization revealed that the mutation actually lay in a base immediately outside the recognition site. Had we included an appropriate double-stranded DNA control in the restriction enzyme digestion of this patient's PCR-amplified exon, we could have arrived at the correct conclusion as to the location of the mutation without incurring high costs and time loss. This brief report depicts the use of DNA controls of appropriate length and base composition as a means of avoiding erroneous conclusions and expense in routine mutational analyses in the clinical setting. PMID- 8197479 TI - Assignment of the human lens fiber cell MP19 gene (LIM2) to chromosome 19q13.4, and adjacent to ETFB. AB - The LIM2 gene may play a major role in lens fiber cell structure or communication, and thus cataractogenesis. A human cDNA encoding the corresponding lens fiber cell intrinsic protein MP19 has been previously isolated and characterized. This cDNA had been mapped to human chromosome 19. We have independently confirmed this assignment and fine mapped it to 19q13.4. The position of the LIM2 gene appears to be within 40 kb of the electron transport flavoprotein gene (ETFB) as a cosmid containing sequences from both genes has been identified. PMID- 8197480 TI - Localization of acyl coenzyme A:cholesterol acyltransferase gene to human chromosome 1q25. AB - Acyl coenzyme A:cholesterol acyltransferase (ACAT) is an intracellular enzyme that catalyzes the formation of cholesterol esters from cholesterol and long chain fatty acyl-coenzyme A. It is believed that ACAT plays a key role in lipoprotein metabolism and atherogenesis. Recently our laboratory succeeded in molecular cloning and functional expression of human macrophage ACAT cDNA. We have now mapped the ACAT gene to chromosome 1, band q25 by using fluorescence in situ hybridization to metaphase chromosomes, and by Southern blotting analysis of human--hamster somatic cell hybrid panels. PMID- 8197481 TI - Vitamin A--time for action. The South African Vitamin A Study Group. PMID- 8197482 TI - Post-discharge follow-up of stroke patients at Groote Schuur Hospital--a prospective study. AB - A survey of 59 stroke patients was undertaken between 3 and 6 months after the event to determine whether a weekly stroke round would improve the rate of referral for rehabilitation. Comparison with a previous survey at Groote Schuur Hospital showed a marked improvement (40% for physiotherapy and 10% for occupational therapy v. 76% and 50% respectively). A comparison of referral rates between younger (< 65 years old) and older patients (> 65 years old) revealed a significantly higher rate of referral among the younger patients. Attendance for both groups was low (approx. 7 sessions per 3 months). Social work was an important requirement and 60% of all patients expressed a need for more help. Social needs of older and younger patients differ. Despite the improved referral rate the rehabilitation of stroke patients is unsatisfactory, mainly because of transport difficulties. Methods should be investigated to establish rehabilitation centres in the community to overcome this impasse. PMID- 8197483 TI - Brain abscess in childhood. A 25-year experience. AB - The presentation, treatment and outcome of 98 children with brain abscesses at Red Cross War Memorial Children's Hospital, Cape Town, is reviewed. Middle ear disease and trauma were the commonest sources of infection in 60% of patients. The usual presentation was that of meningitis and it is recommended that computed tomography be performed before lumbar puncture in those patients with associated middle ear disease, trauma or sinusitis. With early treatment of both the abscess and the underlying source of infection, the mortality rate was 16%. PMID- 8197484 TI - Kaposi's sarcoma in renal transplant recipients. Experience at Johannesburg Hospital, 1966-1989. AB - Between August 1966 and December 1989, 989 renal transplant recipients were followed up at the Renal Transplant Unit of Johannesburg Hospital. Seventy-five (7%) patients developed a total of 95 malignancies of which 5 (6%) were Kaposi's sarcoma. All patients received immunosuppressive agents; steroids, azathioprine and/or cyclosporin A. Clinical presentations included both limited skin involvement (1 patient) and disseminated forms of the disease: necrotic oral lesions (1 patient); disseminated skin involvement and lung metastases (1 patient); and widespread skin lesions with lymphadenopathy (2 patients). Four patients responded with complete tumour regression at all sites upon withdrawal of the immunosuppressive drugs. One patient suffered disease progression, and immunosuppression was continued, albeit at reduced dosages. These cases illustrate a relatively rare complication of immunosuppressive therapy. However, complete withdrawal of immunosuppressive drugs may result in sustained complete regression, despite the presence of advanced KS. PMID- 8197485 TI - Cervical intra-epithelial neoplasia and invasive cervical cancer in black and white patients. AB - The relative incidences of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer were studied in black and white patients at the academic hospitals of the University of the Orange Free State. A statistically highly significant difference was found between black and white patients, with a higher incidence of invasive cervical cancer than stage III CIN (CIN III) in black patients and a higher incidence of CIN III than invasive cervical cancer in white patients (P = 0.000092; 95% confidence interval -0.355-(-)0.128). The time interval between the peak incidence of CIN III and that of invasive cervical cancer was found to be shorter in black than in white patients. These distressing findings emphasise the urgent need for a national cervical cytological screening programme to decrease the incidence of invasive cervical cancer. This serious yet preventable disease is still very prevalent in South Africa, especially among black women. PMID- 8197486 TI - Controversial aspects of intravenous corticosteroids in acute severe asthma. PMID- 8197487 TI - Does coupling of uterine contractions reflect uterine dysfunction? AB - In a cohort analytical study 47 primigravidas in spontaneous normal labour at term were divided into two groups depending on the presence or absence of coupled uterine contractions during active labour. During monitoring with a pressure-tip intra-uterine catheter, 24 patients developed coupled contractions and 23 had a normal contraction pattern. There were no statistically significant differences between the two groups with regard to maternal age, gestational age, maternal height, fetal weight, head circumference and pelvic size. Patients who developed coupled contractions had a longer duration of labour, a higher uterine activity integral and an increased incidence of caesarean section for failure to progress. Because coupling of uterine contractions may be indicative of dysfunctional uterine activity, and hence a prolonged first stage of labour, failure to progress during labour in these patients should be interpreted with caution in order to avoid the incorrect diagnosis of cephalopelvic disproportion. PMID- 8197488 TI - Prevalence of hyaline membrane disease in black and white low-birth-weight infants. AB - Previous studies in South Africa and elsewhere have suggested that there are ethnic differences in the prevalence of hyaline membrane disease (HMD). This study compared the prevalence of HMD between black and white infants with birth weights of 1,000-1,749 g. A cohort of black and one of white low-birth-weight infants were enrolled at Baragwanath and Johannesburg Hospitals respectively. Black infants were found to have a higher rate of intra-uterine growth retardation. When compared according to either birth weight or gestational age categories, black infants had a significantly lower prevalence of HMD. For example, between 29 and 34 weeks' gestation 36.2% of black and 62.5% of white infants developed HMD (P < 0.001). The reasons for these differences are not clear, however, and require further study. PMID- 8197489 TI - Periventricular-intraventricular haemorrhage in low-birth-weight infants at Baragwanath Hospital. AB - The prevalence of periventricular-intraventricular haemorrhage (PV-IVH) among very-low-birth-weight infants at Baragwanath Hospital has not been well documented. In this prospective study, a total of 282 live-born infants with birth weights of 1,000-1,749 g were studied over a 4 1/2-month period. Every infant had at least one cranial ultrasound examination at 7-10 days of age, while one-third of non-ventilated and all ventilated infants had ultrasound examinations on days 3, 7 and 14. Where possible, all infants had a follow-up ultrasound scan at 40 weeks' post-conceptional age. The overall prevalence of PV IVH was 53% for infants weighing less than 1,500 g at birth and 52% for infants born at less than 35 weeks' gestation, but only 12% had either grade III or grade IV haemorrhages. The prevalence and severity of PV-IVH increased with both decreasing birth weight and decreasing gestational age and was also predicted by the need for active resuscitation at birth, mechanical ventilation and the development of pneumothorax. A total of 93% of infants without PV-IVH survived, but survival decreased with increasing grade of PV-IVH. Germinal matrix cysts were noted on follow-up in 55% of surviving infants with grade I PV-IVH. Very-low birth-weight infants at Baragwanath Hospital therefore seem to have a higher prevalence of PV-IVH when compared with reported figures, but this is due mainly to an increase in smaller haemorrhages. PMID- 8197490 TI - Attitudes of women towards traditional midwives--a survey in the Kgalagadi (Kalahari) region. AB - Two hundred and forty-nine women of childbearing age from 20 villages in the Kgalagadi (Kalahari) desert region, who had borne a child, were asked about their attitudes towards institutional and non-institutional deliveries. Two hundred and two (81.6%) women preferred to give birth at home. One hundred and seventeen (46.9%) attended antenatal clinics at health facilities but virtually none of these attended postnatal clinics. Forty-one per cent of the women who prefer to give birth at home do so because at home they receive African 'muti' and an abdominal massage; 22.5% deliver at home because they feel it is safer and more convenient. Most African women and communities are reluctant to entrust the sluicing of their placenta and other products of conception to strangers such as nurses. Ninety per cent of respondents suggested that traditional midwives and health personnel should work together to improve community maternal health services. PMID- 8197491 TI - Visual function and long-term chloroquine treatment. AB - Ophthalmic examinations and selected tests of visual function were performed on 64 patients with rheumatoid arthritis who had received daily doses of 200 mg chloroquine sulphate for periods ranging from 3 to 11 months. Visual fields were determined by Humphrey automated perimetry and Amsler grids and a further battery of four tests of macular function (visual evoked potentials, critical flicker fusion threshold, Cambridge contrast sensitivity and the macular dazzle test) were administered. No case of retinal pigmentary abnormalities plus visual loss was found, but 2 patients were advised to cease chloroquine therapy on the basis of funduscopic findings. A small group of patients with relatively poor scores on one or more tests had normal visual fields and ophthalmic findings. There were no significant partial correlations between test results and the cumulative dose of chloroquine. These results support the opinion that currently recommended doses of chloroquine pose a minimal risk of retinal toxicity. PMID- 8197492 TI - Mood disorders and season of presentation. A preliminary study of an inpatient sample at Baragwanath Hospital. AB - The relationship between season and mood is complex. This study attempts to clarify one aspect of the relationship: the impact of season on mood in terms of the hypothesised seasonal variation in the presentation of mood disorders at Baragwanath Hospital. Although a preliminary study, the results show a statistically significant seasonal trend for presentation of mood disorders, confirming the hypothesis and providing a basis for further study of this phenomenon. PMID- 8197493 TI - Microvascular replantation of avulsed tissue after a dog bite of the face. AB - Various authors have described successful microsurgical replantation of totally avulsed facial tissue. In a significant number of cases difficulties were experienced with the venous anastomoses and/or venous drainage of the tissue. Many different methods were used to overcome the problem. Despite these difficulties, good cosmetic and functional results were reported. These injuries are often caused by animal bites. Adequate wound care and the excellent local blood supply make immediate reconstruction after animal bites of the face a safe procedure. Other authors describing similar lesions and immediate repair have not reported the complication of wound infection. We report on a patient who suffered a dog bite with total avulsion of most of the left upper lip, cheek and left alar rim. Venous congestion was overcome by multiple needle punctures to drain blood from the outer surface of the flap and local of application of heparin. A good cosmetic result and the return of sensation and function of the orbicularis oris muscle were obtained. PMID- 8197494 TI - Avascular necrosis and cortisone. PMID- 8197495 TI - Our future health system. PMID- 8197496 TI - Making essential health information accessible. PMID- 8197497 TI - Centres of excellence for academic medicine in South Africa. PMID- 8197498 TI - Assessment of mental health problems. PMID- 8197499 TI - Margarine and coronary heart disease. PMID- 8197500 TI - Uterine inversion--a life-threatening condition. PMID- 8197501 TI - Psychiatric classification--an ongoing process. PMID- 8197502 TI - Effect of closure of holes in air entrainment oxygen masks. PMID- 8197503 TI - Emergency medicine in South Africa. PMID- 8197504 TI - Marked hypokalaemic rhabdomyolysis due to purgative abuse. PMID- 8197505 TI - [Anticholinergic intoxication delirium-- a life threatening condition]. PMID- 8197506 TI - [Basal secretion of endogenous opioids after intravenous naloxone]. PMID- 8197507 TI - Ganglioneuroma of the sympathetic chain simulating tuberculosis of the mesenteric glands. PMID- 8197508 TI - Intrahepatic biliary stones in South Africa. PMID- 8197509 TI - Beware of voluntary agreements with the tobacco industry. PMID- 8197510 TI - Plastic surgery--more than just a nip and tuck. PMID- 8197511 TI - Orthopaedics and health care in South Africa--yesterday, today and tomorrow. PMID- 8197512 TI - [Gaucher's disease. Forget the past?]. PMID- 8197513 TI - [HIV and blood donors: past, present and future]. AB - PURPOSE: To evaluate the changes in the spectrum of HIV-positive blood donors along seven years. PATIENTS AND METHODS: The municipal Blood Bank of Caracas Federal District examined 193,796 blood donors between 1986 and 1992. Anti-HIV antibodies were determined by the following methods: Ortho HIV-Elisa Test System (59.5% of the samples), Abbott Recombinant HIV-EIA (28.6%), Vironostika HIV Microelisa System-Organon Teknika (2.1%), Bio-Test anti-HIV Recombinant Elisa (2.1%), and Recombigen (env and gag) HIV Cambridge Biotech (7.7%). Results confirmation was performed with Biotech/Dupont HIV-I Western Blot Kit, Chiron Riba HIV 216 Test System and Inno-Lia HIV 1/2 Ab immunogenetics SA. RESULTS: Slow but progressive increase of positive results was seen in the blood donors along the years, from 0.05% in 1986 to 0.31% in 1992. Higher prevalence was seen in males (p < 0.001), although absolute increase in the number of positive females was found by 1992 (p < 0.05). According to their type, 80.6% of the donors were patient-related (RD), 13% attended mobile blood-drawing units (MU) and 6.4% were VD (p < 0.001), with a trend to increase amongst DR and decrease amongst MV. The majority of the positive donors pertained to homo-or bisexuals (60.5%), although they showed progressive decrease, whereas the positive findings increased in the promiscuous heterosexual group and amongst those having contacts with persons at risk. CONCLUSIONS: High prevalence of HIV-positive donors is found, the expected figure for 1995 being 0.37% if the present trends are maintained. Thus, a better selection of blood donors is recommended by means of careful enquiries, the use of optimal reagents capable of shortening the window period, deferring people at risk from blood donation, and promoting altruistic voluntary donation of blood. PMID- 8197514 TI - [Evaluation of the fibrinolytic system in myocardial infarction]. AB - PURPOSE: To evaluate the main components of the fibrinolytic system in patients suffering of acute myocardial infarction (AMI), both in the acute phase and once this has been overcome. PATIENTS AND METHODS: Components of the fibrinolytic system (i.e., PAI-1, t-PA, fibrinogen, plasminogen, and alpha 2-antiplasmin) were determined in 100 patients with AMI. The studies were performed at AMI and 6 months later, and the findings were compared with those of a control group of 30 people matched with regard to age and sex with the patient group. The statistical analysis of the results was made with the BMPD pack, using Student's t test for comparing quantitative variables and the matched test for paired samples. RESULTS: At the acute phase the patients showed significant increase of PAI-1 (p < 0.001) and fibrinogen (p < 0.05) concentrations. Plasminogen and alpha 2 antiplasmin rates were lower than in the control group (p < 0.01 and p < 0.005, respectively). In the 6-month study after AMI, significant increase of PAI-1 was found with respect to the control group (p < 0.001). There were also significant differences in the initial PAI-1 rates and the 6-month test (p < 0.05), whereas the increased fibrinogen rates persisted (p < 0.01). Increased antigenic t-PA was found in the patient group before venous occlusion (p < 0.001). Thus, 54 patients (54%) had hypofibrinolysis, due to increased PAI-1 in 41 cases (41%), impaired t PA release in 13 cases (13%) and both causes in 12 cases (12%). CONCLUSIONS: Fibrinolytic hypofunction was found in this study during the acute phase of myocardial infarction, which was still present six months later, and was due to increased PAI-1 rates in the majority of the cases. PMID- 8197515 TI - [Reference values for vitamin B12 in blood in a population of children and one of adults using the IMxRB12 method]. AB - In this study we have performed the reference values of vitamin B12 of a population of 124 children aged 0-18 years and 42 adults aged 19-55 years, assessed by the recent method IMxR B12. Abbott. The population studied included outpatients, some inpatients and groups of subjects undergoing banal examinations in the Hospital Universitario Materno-Infantil of Barcelona. STATISTICS: Data were first tested for goodness-of-fit gaussian distribution by a nonparametric test, by testing skewness and kurtosis coefficients for significance and by Kolmogorov-Smirnov test. The correlation with the age groups was evaluated with Student's-t-test. RESULTS: We show the histograms of the data obtained and a nonparametric approach selecting the central 95th percentile range. Reference limits (5-95th percentile range) were as follows: Premature infants = 365-1568 ng/L; 1-3 years = 345-1154 ng/L; 4-6 years = 330-1236 ng/L; 7-11 years = 312-1237 ng/L; 12-18 years = 328-1185 ng/L; Adults (19-55 years) = 300-964 ng/L. There were no significant differences between both sexes. The goodness-of-fit test for a gaussian distribution showed no departure from normality except for the groups of children 12-18 years old. A simple linear regression analysis showed that age significantly affected the concentration in inverse way. CONCLUSIONS: The importance of establishing the reference values of vitamin B12 lies in the relevance of this serum analyte to some pathophysiological conditions. Considerable racial heterogeneity exists in populations, and these racial differences profoundly affect total values of vitamin B12 so that different racial reference limits have been suggested. PMID- 8197516 TI - [Type I Gaucher's disease: clinical, evolutive and therapeutic features in 8 cases]. AB - PURPOSE: To analyse the clinical features, course and treatment of a group of patients with type I Gaucher's disease. PATIENTS AND METHODS: The study comprises 8 patients diagnosed in childhood or young age, except for one, diagnosed in adulthood. The follow-up ranges from 1 to 26 years (mean, 15 years). The diagnosis was usually established by identification of Gaucher cells in the bone marrow or other tissues; enzyme and genotype studies were performed in 5 cases. In the patients receiving substitutive therapy with Alglucerase the dosage was 5 U/kg/day twice a week (2 cases) or 30 U/Kg every second week (1 case). RESULTS: The mean age of the patients at diagnosis was 22 years (range, 4-52) and the M/F ratio was 1.0. Splenectomy was carried out in 5 of the 8 cases between 2 months and 13 years since diagnosis, because of severe cytopenia due to hypersplenism; severe haemorrhage appeared in two cases. Prophylactic antibiotics against capsulated germs were given to all the patients undergoing splenectomy, no infectious episodes appearing in their clinical course. Lipid deposition hepatomegaly was present in 7 cases, ranging between 2 and 20 cm.; Gaucher cells and fibrosis were seen in liver biopsies. Skin involvement was present in one case, and pingueculae in 6. Bone lesions were seen in 5 patients. Neurological manifestations were absent in every case. Positive serology for CVH was found in 3 cases and for BVH in one other. Alglucerase treatment: Striking clinical improvement was seen six months after starting this therapy, hepatomegaly being reduced in 9 cm in case No 1, while pain and hip dysfunction subside in case No 2 and blood cell counts recovered in case No 3. No adverse side-effects were appreciated with this treatment. COMMENTS: Gaucher's disease is an unusual disorder, with ill-defined incidence in our environment. The commonest symptoms include cytopenia and/or visceromegalia. The clinical course is usually torpid, with high morbidity requiring hospitalization due to haemorrhage, surgery or bone complications in most cases. Better long-term prognosis can presently be expected in view of the good response to substitutive therapy. In order to establish an adjusted evaluation of the disease and its economic implications, a national registry would be desirable, thus allowing us to know the actual incidence and to make plans for successful Alglucerase treatment, taking into account the high costs of this last. PMID- 8197517 TI - [Bone marrow granulomas]. AB - PURPOSE: To evaluate bone marrow granulomatous lesions in order to establish their etiology. MATERIAL AND METHODS: 2,250 bone marrow biopsies were studied during the period of March 1983-March 1991. Granulomas and/or granulomatous lesions were found in 24 of them (1.06%). A correlation between histological characteristics, special stains: PAS, Ziehl Neelsen and Grocott and cultures were done. Immunohistochemistry was done to evaluate B or T cell-lineage in 4 patients. RESULTS: The 24 patients were biopsied because of the clinical diagnosis of haematological and non-haematological neoplasias, infections, AIDS, sarcoidosis and fever of unknown origin. Bone marrow cellularity ranged from 20% to 75% (M: 49.8%). Myeloid cells were increased in 54% of the cases. The number of granulomas ranged from 1 to 19 (M: 3.9). The epithelioid cells were the predominant component in 66% of the cases. Of the 7 patients with non-Hodgkin's lymphoma, 4 had lymphomatous involvement with granulomatous pattern. These cases showed predominance of lymphoid cells and vessels in addition to epithelioid cells. CONCLUSION: We consider that in order to establish a relationship between infection and granuloma, the identification of a microorganism through a culture is a more reliable test. We couldn't find any morphological characteristic which allowed an etiologic diagnosis of bone marrow granulomas. In case of lesions with a great lymphocytic and vascular proliferation plus the presence of epithelioid cells and fibrosis, NHL with bone marrow involvement with a granulomatous pattern should be strongly considered. PMID- 8197518 TI - [Current therapeutic focus in type I Gaucher's disease]. PMID- 8197519 TI - [AEL: a rare variant of blood group A]. AB - We have studied an eight-member family. Three of them presented discrepancies between red blood cell and serum tests. The red blood cells fail to react with anti-A, anti-B or anti-AB of any origin. On the other hand, serum grouping tests strongly react with group B cells and fail to react with A1 and A2 cells. Then we performed saliva and adsorption/elution studies in order to demonstrate A or H substances in saliva of secretors. We conclude that the blood belonged to an A weak group named Ael. PMID- 8197520 TI - [Visceral leishmaniasis presenting with peripheral leukocytosis and lymphocytosis]. PMID- 8197521 TI - [Primary lymphoma of the uterine cervix]. PMID- 8197522 TI - [Chronic myeloid leukemia (CML) and solid neoplasms. Description of 3 cases]. PMID- 8197523 TI - [Hodgkin's disease following non-Hodgkin's lymphoma]. PMID- 8197524 TI - [Pleomorphic T-lymphoma associated with chronic myelomonocytic leukemia]. PMID- 8197525 TI - [Necrotizing lymphoma]. PMID- 8197526 TI - [Determination of serum ferritin: ideas for avoiding induced ferropenia in blood donors]. AB - PURPOSE: To evaluate blood donation as a cause of iron deficiency. MATERIAL AND METHODS: Serum ferritin levels were determined by enzymoimmunoassay with an SRItm autoanalyser in 500 blood donors of both sexes chosen at random and in 200 suitors for blood donation, used as control group. Iron deficiency was defined by ferritin values below 15 ng/dL. Age, sex, total number of blood donations and those carried out in the last year were all correlated for the statistical analysis, performed with the SPSS/PC+ pack. RESULTS: The mean ferritin value in men was 86.0 ng/dL, and in women this was 27.1 ng/dL. With respect to the control group, blood donors showed increased iron deficiency, 7.4% for men and 11.8% for women. Highly significant direct correlation was found in male donors between total donations, last-year donations and age, and between total number of donations and age in female donors; highly significant inverse correlation was found between total number of donations, last-year donations and ferritin levels among the male donors, while these correlations lacked significance in the female donors. When correlating last-year donations with mean ferritin levels in women, low, although constant, ferritin values were seen, whereas a marked descent was found in men. Iron deficiency was strikingly spread among women, ranging between 21% of those with one blood donation to 46% in those with 4 donations during the last year; in men, iron deficiency was present in 14% of those with 4 or more blood donations in the last year. With respect to total number of blood donations and mean ferritin values, iron deficiency was found in 50% of the women with 8 donations and in 12.8% of men with 14 donations. Ferritin levels decrease in blood donors with aging beyond two blood donations in both sexes. CONCLUSIONS: 1st) Iron deficiency related to blood donation is demonstrated. This deficiency is clearly seen in men after the first blood donations and is more intense in women, as their previous reserves are lower. 2nd) Ferritin is the best marker for estimating iron deposits, and enzymoimmunoassay is the technique of choice as it seems easy to perform and is automatic. 3rd) Determining ferritin levels in the first blood donation seems advisable in order to assess previous deposits and to evaluate yearly the state or iron reserves. 4th) Iron supplement is advisable during the 4 first donations in regular blood donors and in those with iron deficiency, with ferrous sulphate at a dose of 100 mg/day for 10 days. PMID- 8197527 TI - Principles of antibiotic therapy. AB - The primary development in the area of antibiotic treatment for surgical infections in the last 5 years has been the expanded clinical importance of beta lactamases in the protection of Gram-negative organisms from previously active drugs. To counter this problem, a series of new antibiotic agents has been developed, including new cephalosporins, carbapenems, quinolones, and beta lactamase inhibitors. This article describes the various beta-lactamases and their mechanisms of action, and details the activity of new antibiotic agents against resistant Gram-negative organisms. Recent information on the importance of combination therapy for patients with severe Gram-negative infections is reviewed. The use of optimized aminoglycoside dosing regimens, including once-a day dosing, provides an additional strategy for treating serious Gram-negative infections. PMID- 8197528 TI - Wound infections. AB - Wound infections continue to be an important entity in terms of use of time and medical resources. Currently, the following risk factors are known to strongly predispose to wound infection: pre-existing medical illness, prolonged operative time, wound contamination, and contaminated or dirty wounds. Tissue level factors, including the local microenvironment, white cells, and cellular products that mediate inflammation, are important, and their manipulation holds promise for future therapies. For now, the judicious use of antibiotic prophylaxis and organized systems of wound surveillance are the most effective means to reduce the wound infection rate to its pathophysiologically attainable minimum. PMID- 8197529 TI - Diabetic foot infections. Pathophysiology and treatment. AB - Foot infections are among the most common reasons for hospital admission of the diabetic patient. A diabetic foot infection represents a failure by the patient and his management team to understand and correct the multifactorial conditions that predisposed the patient to the infection. Efforts directed toward prevention of the foot infection are much more likely to meet with success than is therapy of the established foot infection. This preventive approach is likely to lead to a reduction in the incidence of major amputations and thereby improve life expectancy. Understanding the pathophysiology associated with the diabetic foot is essential to the care of the diabetic patient. If a breach in skin integrity occurs, prompt assessment of vascular, neural, soft tissue, and wound status enhances the possibility of a successful clinical outcome. The complexity of the management of a diabetic requires the knowledge and skill of a multidisciplinary team, which usually includes an internist, podiatrist, rehabilitation specialist, prosthetist, dietitian, and social worker in addition to a surgeon interested in caring for the complications of diabetic feet. The goals of this multispecialty group are to optimize local wound care, provide correct foot wear, improve glucose control, educate the patient concerning diet and life style changes, and identify the presence of peripheral neuropathies and reconstructable arterial lesions. This combined medical team approach has been documented to substantially reduce the incidence of major and minor amputations in the diabetic. PMID- 8197530 TI - Intravenous and central catheter infections. AB - Catheter-associated infections are quite common in hospitalized patients and account for significant morbidity and mortality. Multiple causative factors are present in everyday clinical practice to account for these infections. A high index of suspicion for these infections is needed in any evaluation of a patient who has a febrile illness. Removal of the catheter and quantitative culture are necessary initial steps in treatment, and systemic antibiotic therapy, based on specific culture results, is indicated in any patient whose systemic signs of infection do not resolve promptly. In the absence of such a response, other sources of infection should be sought; however, one must maintain a high index of suspicion for the local site of catheter insertion, and repeated examination of all insertion sites is indicated until the fever resolves. PMID- 8197531 TI - Prosthetic graft infection. AB - This article outlines the tenets and basic data critical for the management of prosthetic graft infections. Diagnostic algorithms and treatment options appropriate for patients with symptoms and signs suggestive of graft infection are presented. PMID- 8197532 TI - Necrotizing soft-tissue infections. AB - In the realm of clinical practice, this disease entity defies applicability to any classification scheme. Of paramount importance is the early identification of all necrotizing soft-tissue infections. This requires a high index of suspicion, aided by recognition of various risk factors and organ system dysfunction out of proportion to the extent of local signs and symptoms. Expedient, aggressive surgical therapy is imperative: resuscitation, wide debridement, and antibiotic therapy. Once the infection has been controlled, continued supportive care, reconstruction, and rehabilitation can proceed. PMID- 8197533 TI - Infections in the immunocompromised patient. AB - Specific microorganisms have certain types of host defenses directed at them. Inhibition of different host defenses, therefore, leads to an increased risk of the host for infection with different organisms. This article discusses the types of infections present in immunocompromised patients as well as a general approach to diagnosis and treatment. PMID- 8197534 TI - Gram-negative bacterial sepsis and sepsis syndrome. AB - Gram-negative bacterial sepsis and septic shock remain significant causes of morbidity and mortality in hospitalized patients. Recent investigation in this area has served to better define the host response to these and other types of infection, a constellation of signs and symptoms that has been termed sepsis syndrome. Recent studies indicate that the mortality associated with this latter disease process is approximately 40%, despite administration of antimicrobial agents, hemodynamic monitoring and fluid resuscitation, and metabolic support. For this reason, the pathophysiology of this process is undergoing intensive examination, and attempts are being made to employ several new types of treatment modalities as adjunctive therapy. Although the initial antiendotoxin antibody trials have not demonstrated the efficacy of these reagents, these studies have provided extremely valuable information regarding appropriate trial design, the current epidemiology of sepsis syndrome (particularly in relation to the ensuing morbidity and mortality), and the pathophysiology of the host septic response and have highlighted the need for rapid, precise diagnostic assays. A number of other intriguing reagents, including anti-TNF-alpha antibody preparations, IL-1ra, bacterial permeability-increasing protein, TNF-binding protein, polymyxin B hemoperfusion, and lipid A analogues also are undergoing experimental and clinical testing in an attempt to reduce the mortality of this lethal disease process. PMID- 8197535 TI - Physiologic support of the septic patient. AB - The patient's response to inflammation, referred to as sepsis, is a complex process involving the degree of the inflammatory insult and the host response. Ischemia, from blood flow abnormalities and direct cell injury from mediators, produces the physiologic response. The treatment is focused first on restoring and maintaining perfusion through maintenance of increased oxygen delivery. The second approach is first surgical then pharmacologic attenuation of the inflammation-induced injury. PMID- 8197536 TI - Nutrition and infection. AB - It is now apparent that nutritional status has a profound impact on immune function and that the immune system may be modulated by the use of specific modes of nutritional support. In selected malnourished or severely injured patients, early nutritional support has been shown to improve outcome and decrease the incidence of infectious complications following major surgery or trauma. Enteral feedings appear to support the immune system better than parenteral feedings. TPN, although a potentially life-saving modality, should not be used indiscriminantly and should be limited to those severely malnourished or injured patients who are incapable of tolerating enteral feedings. The patient's metabolic needs should be assessed as accurately as possible, and the appropriate combination of substrates should be provided according to the patient's level of hypermetabolism. Overfeeding should be avoided. A number of nutritional substrates have been identified which may potentially modulate specific aspects of immune function. Among these, glutamine, arginine, and omega-3 fatty acids have demonstrated potential clinical usefulness. Iron deficiency appears to be a normal host defense response to infection or trauma and should not be compromised by attempts at iron replacement therapy. In summary, optimal nutritional support of the surgical patient supports the immune system and reduces the morbidity and mortality associated with severe malnutrition or injury. PMID- 8197538 TI - Noninvasive imaging tests in the diagnosis and treatment of intra-abdominal abscesses in the postoperative patient. AB - The postoperative surgical patient poses special problems in the diagnosis of intra-abdominal abscess. A natural evolution has occurred over the last 20 years from purely clinical impressions being used to initiate reoperations for abscess to the present scenario, in which sophisticated CT scans permit minimally invasive drainage methods. The CT scan has become the diagnostic imaging method of choice, with other techniques serving a very limited role at the present time. PMID- 8197537 TI - Therapeutic options in peritonitis. AB - The fundamental principles of management of peritonitis include general supportive management, antibiotic therapy, and prompt surgical intervention. Several empiric antibiotic regimens have proven to be effective. All have in common activity against gram-negative bacilli and anaerobic bacteria. The choice of a particular regimen depends primarily on patient-specific factors. Surgical intervention includes source control, peritoneal toilet, and prevention of recurrent infection. Control of the source of contamination involves resecting, excluding, or patching the diseased viscus at laparotomy or, more recently, laparoscopic methods in selected cases. Attempts to prevent recurrent infection using intraoperative saline lavage and radical peritoneal debridement have shown no benefit in well-designed clinical trials. The roles for continuous postoperative peritoneal lavage, planned relaparotomy, and laparostomy in the current management of severe peritonitis remain to be established. PMID- 8197539 TI - [The importance of neuromuscular coordination for athletic stress of the knee joint after anterior cruciate ligament injuries. A gait and locomotion analysis with EMG on treadmill]. AB - Anterior cruciate ligament (ACL) injuries are considered of high prevalence in sports medicine and are of socio-economical relevance. Indications for operative treatment and the ability for physical activity after ACL injuries are discussed controversially. Although it is known that the ACL has neurosensory functions, no test system has been developed which takes this biological function into account. The first goal of this study was to determine the neurosensory function after ACL reconstruction, and the second goal was to develop predictive markers for functional results after surgery. 20 healthy athletes (10 male, 10 female) (control group) and twenty ACL deficient patients (10 male, 10 female) (study group) were included in a prospective, controlled study. Electromyograms (EMG) were performed under defined load conditions of the knee. Important results of our study are: 1. Previously described parameters can be reproduced with EMG techniques. Their validity was proved. Typical contraction patterns (m. quadriceps, hamstrings, m. gastrocnemius) for defined load conditions can be recorded. 2. Statistically significant differences can be shown between the control group and the study group as well as between the two legs (injured/noninjured) of the same patient in the study group. 3. The results suggest that the diminished innervation of the m. biceps femoris and m. gastrocnemius in down-ramp-running as an important parameter for ACL deficiency. 4. Distinct differences of innervation patterns of the muscles, which stabilise the knee in downramp walking suggest that despite a subjective stability, altered load conditions may result. Innervation patterns seem to vary from individual to individual. 5. Concluding from our findings, we suggest that clinical methods should be developed to allow a patient-specific assessment of physical activity. PMID- 8197540 TI - [Distal femoral fixation of the iliotibial tract]. AB - Two femoral fixation areas were defined in the distal iliotibial tract (ITT) system. They were named supracondylar insertion and insertion near the septum. Biomechanical studies on these insertions revealed tension peaks in the insertion near the septum with anterior translation of the knee, with varus stress and rotational movements. We conclude that the fibers inserting here are secondary restraints against anterior and lateral knee instability. 5 lateral extraarticular procedures were investigated to evaluate their biomechanical effect on knee instability. A standardized cadaver knee model was used with two basic experiments: an excentric quadriceps contraction from 0 to 90 degrees of flexion and an anterior translation with 100 N in 30 degrees of flexion. 5 knees were investigated for each procedure. Results from the excentric quadriceps contraction study imply reduced ACL strain with all extraarticular procedures except the Andrews tenodesis. The quantitative effect was related to the mechanical strength of the fixation of the ITT. All lateral procedures reduced ACL strain with anterior translation of the knee. The last part of the study included simultaneous registration of rotation and translation of the knee. We demonstrated a close relation of decreased ACL strain due to a lateral procedure and pathological external rotation of the knee. The knee no longer reached the physiological neutral rotation angle after an effective lateral tenodesis procedure. The significance of this effect is not clear at the present time. PMID- 8197541 TI - [(Neuro)muscular changes in the knee stabilizing muscles after rupture of the anterior cruciate ligament]. AB - Recent data indicate that the function of the knee joint may be the result of a complex synergy between bones, ligaments, muscles and proprioceptive receptors in these structures. Therefore, it was the aim of this study to investigate if muscular changes could be found more than 5 years following ACL-injury and if there are therapy-dependent differences. 35 patients with ACL-reconstruction and 25 conservatively treated patients were studied. The thigh circumference was measured and in 5 randomly selected patients of each group additionally MRI cross sections of both limbs were made. Using an isokinetic dynamometer and an EMG device the relation of strength, electrical activity and muscle size were analyzed. Only minimal differences in thigh circumference as well as in muscular cross sections were found between the uninjured and injured limb of both groups; however, the isokinetic torque and iEMG values showed significant differences. It may be assumed that the major reason for these results is a modified muscle fiber utilization in the ACL-injured limb, caused by a changed joint receptor afferent inflow or a compensation of the central nervous system to primary alterations of the muscle fibers. PMID- 8197542 TI - [Injuries in snowboarding--a prospective study]. AB - 180 patients with injuries effected through snowboarding were evaluated during a period of 2 1/2 months in both the hospitals and private surgeries of Oberwallis. This was done to determine the nature of the injuries and the risk factors that led to them. Snowboarders are on the average 21 years of age and only rarely over 40. One-third are women, and two-third are men. More than half are beginners with less than one week's training experience; one-fifth of the beginners met with the accident on the first "snowboard day". Over 80% of the injured said that riding mistakes and insufficient training and instruction were the cause; rarely were the conditions of the runway blamed. The accidents happened irrespective of snow and runway conditions. Accidents due to tearing of the fastenings always injured the lower extremity. Injuries of the upper and lower extremities take place in the same proportions. Injuries of the trunk and head are rare. Beginners usually injure the upper, while good snowboarders the lower extremities. The most common injuries are radius fractures, followed by ankle and knee distorsions. In the case of injuries to the lower extremities, the forward leg which is the "skating leg" or "standing leg", is affected more than 80% of the cases. PMID- 8197543 TI - [Stress-related long-term changes of the menisci]. AB - In 82 asymptomatic subjects aged 8 to 62 years we evaluated the menisci by MRI (1.0 tesla; Spin-Echo (SE 700/20), PS (Partial Saturation) (500/10), STIR (Short Time-Inversion-Recovery-Sequence; 1600/130/30). For grading the degeneration of the meniscus we used a standard classification (grade 0-4). MR-findings were correlated with the patients' age, weight, profession, and athletic activity. Statistic analysis revealed a correlation between athletic activity and meniscal degeneration of the anterior horns as well as of the lateral meniscus. Especially the anterior horn of the lateral meniscus seems to be loaded during athletic activities. Correlation of meniscus degeneration with subjects' age showed an increase of grade 3 and grade 4 lesions with advancing age. Subjects older than 50 years presented grade 3 and 4 lesions in the SE-sequence in 28.5% of the cases, in PS-sequences in 40.7% of the cases, and in STIR-sequences in 25% of the cases. CLINICAL RELEVANCE: Athletic activity seems to load the anterior knee compartments especially the lateral compartment. In asymptomatic subjects MRI shows meniscal lesions in a significant number of patients, especially in subjects older than 50 years. PMID- 8197544 TI - [Meralgia paraesthetica in a body-builder]. AB - The article describes the case of meralgia paraesthetica, a disease not uncommon, of a bodybuilder. Extensive literature of meralgia paraesthetica shows us several reasons for the injury of the lateral cutaneous nerve of the thigh, but the genesis of the nerve-injury by strain in training is unusual. Diagnostics and therapy of that disease do not present any difficulty. PMID- 8197545 TI - [Frontal sinus impression fracture as a collision sequelae in football]. AB - 4 soccer accidents, causing the rare case of impression fracture of the frontal sinus, are introduced as soccer-specific lesions, which are caused by head-to head collisions, being due to heading-maneuvers. Mostly the right frontal sinus was hurt. The indication for an operation is the obvious dislocation of the osseous fragments. Primary intentions for an intervention are the precise reconstruction of the anterior wall of the frontal sinus because of esthetic reasons and a permanent drainage in order to avoid late complications as for instance mucopyoceles, if the infundibulum has been damaged. The therapy of choice is the osteoplastic frontal sinus operation, using a bicoronary incision. PMID- 8197546 TI - [New aspect of the pierced wire osteosynthesis technique]. PMID- 8197547 TI - New understanding from Cf brachytherapy trials and considerations for neutron therapy of bulky gyn carcinoma for future. AB - PURPOSE: This study reviews the radiobiology of neutrons and the results and methods that have evolved in the Cf-252 neutron brachytherapy trials to postulate methods to explore for their potential applicability to fast neutron beam therapy. METHODS AND MATERIALS: The results of radiobiological experimental studies are reviewed for RBE for different fraction number and dose per fraction. RBE was always higher for fractionated neutrons based on comparison with isoeffective doses of photons. This is inherent in the basic radiobiological properties of photons. RBE was highest for low dose rate (LDR) Cf brachytherapy. RESULTS: Brachytherapy methods deliver radiation dose which is localized and conformal to the tumor. These methods have been used for Cf therapy and led to good tissue tolerance and local tumor control. The use of large dose/session (or fraction), small fraction number, short treatment times, followed by photon beam therapy has been the practice in Cf brachytherapy. It has been found that bulky or localized advanced tumors responded better if neutron treatment preceded the photon beam therapy. Therapeutic efficacy is dependent on the fraction size of neutrons and not the time duration of application. CONCLUSIONS: Available radiobiological data on neutron RBE with fraction number and size of dose and the favorable experience from Cf brachytherapy with up-front neutron applications suggest new avenues to explore for the neutron beam trials. The high efficacy noted for small volume dose, 10 to 20 Gy-eqs of dose per session, localized dose, conformal methods, small number of sessions, short treatment times and an up front or early schedule in combining neutron and photon therapy suggests that similar schedules and methodology may also be effective for neutron beam therapy. Further clinical trials are indicated and bulky GYN tumors represents suitable tumors for study. PMID- 8197548 TI - [The methods and results of simultaneous radiochemotherapy with carboplatin in advanced cervical carcinomas]. AB - PURPOSE: The frequency and the poor therapeutic results in advanced cervical cancer establish the demand for effectiveness of treatment. Recent clinical data have shown that simultaneous radiochemotherapy may yield high remission rates in squamous cell carcinomas of other organs. PATIENTS AND METHODS: In our Department of Radiotherapy and Radiooncology of the University of Leipzig we treated since 1.6.1991 17 patients with advanced cancer of the uterine cervix with a simultaneous radiochemotherapy with carboplatin. RESULTS: The rate of complete remission was 76%. Follow-up is available from six to 24 months. Severe or toxic side effects of the treatment we didn't observe. Eight (47%) patients live relapse-free. CONCLUSIONS: In our opinion randomized studies are required to determine: What is better? Simultaneous radiochemotherapy or radiotherapy? PMID- 8197549 TI - Long term follow-up results of high-dose rate remote afterloading intracavitary radiation therapy for carcinoma of the uterine cervix. AB - PURPOSE: High-dose rate remote afterloading intracavitary radiation therapy (HDR) has been used as more safety system by the dose calculation using computer system before treatment and dose monitoring system using semiconductor dosimeter (ICD 5). This study shows our long-term follow-up results concerning survival, prognostic factor and late complications. MATERIAL AND METHODS: Between August 1978 and December 1982, a total of 200 patients with carcinoma of the intact uterine cervix were treated using HDR. According to the staging system of UICC (1987), 8 patients were classified into Stage Ia, 22 Ib, 22 IIa, 53 IIb, 85 III, and 10 IV. RESULTS: Cause specific five- and ten-year survival rates by Stage were 100%, 100% in Stage Ia, 90%, 90% in Stage Ib, 76%, 76% in Stage IIa, 86%, 84% in Stage IIb, 54%, 46% in Stage III and 20%, 20% in Stage IV, respectively. Significant prognostic factors by Cox's multivariate analysis were stage (p = 0.0001), the value of hemoglobin (p = 0.0005) and older age (p = 0.0114). Concerning stage classification the value of hemoglobin was the most important prognostic factor in Stage II (p = 0.032) and Stage III (p = 0.0015). Late complications requiring medical treatment after RALS developed in 24 patients (12%), i.e., rectum 14 (7), bladder 8 (4), small intestine 5 (3), sigmoid colon 1 (1). Severe complications requiring surgery were noted in 9 patients (5%). CONCLUSION: HDR yields good results of survival with a low risk of severe side effects for the treatment of carcinoma of uterine cervix based on our long-term follow-up results. PMID- 8197550 TI - Radical radiation therapy for adenocarcinoma of the uterine cervix. AB - PURPOSE: Analysis of the therapeutic value of radical irradiation for patients with uterine cervical adenocarcinoma with special reference to pelvic disease control. PATIENTS AND METHODS: 20 patients with uterine cervical adenocarcinoma were treated with a combination of external beam and intracavitary irradiation (four patients stage IB, one stage IIA, three stage IIB and twelve patients stage IIIB). Seven patients were treated with high dose-rate (HDR) intracavitary irradiation, eleven with low dose-rate (LDR) intracavitary irradiation and two with HDR and LDR. RESULTS: Six out of the 20 patients experienced pelvic recurrence (all stage IIIB patients). Analysis of the relation between pelvic recurrence and dose rate of intracavitary irradiation revealed that LDR showed a higher pelvic disease control rate than HDR (6/7 vs. 0/4) in stage IIIB patients. Intracavitary irradiation doses of LDR were 1.2 to 1.5 times higher than those of HDR. Three out of the 20 patients developed rectal complication grade 2 (two patients treated with HDR, one with LDR). The five-year cumulative survival rate was 67.2% for all, 100% for stage I and II, and 43.3% for stage IIIB patients. CONCLUSION: These results suggest that locally advanced uterine cervical adenocarcinoma should be treated with a higher dose using LDR intracavitary irradiation. If adequate total doses can be delivered, pelvic disease control of uterine cervical adenocarcinoma is comparable with that achieved for squamous cell carcinoma. PMID- 8197551 TI - [Pre- and postoperative radiotherapy to prevent heterotopic ossification of the hip joint]. AB - BACKGROUND: In-vivo experimental data indicate that both pre- and postoperative radiotherapy can prevent heterotopic ossification after hip surgery. This comparison was clinically tested in a randomized study. PATIENTS AND METHODS: From June 1992 to September 1993, 84 patients with high risk for the development of heterotopic ossification were randomized. The treatment concept consisted either of preoperative radiotherapy within four hours prior to surgery (arm A) or postoperative radiotherapy within 72 hours following hip surgery (arm B). Preoperative radiotherapy was given in one fraction of 7 Gy, while the postoperative radiotherapy was delivered in five fractions of each 3.5 Gy (total 17.5 Gy). All patient variables (age, sex, prior surgery) and predisposing risk factors were comparable in both treatment arms. For the radiological assessment of heterotopic ossification according to (Brooker-Score) X-rays of the pelvis or hip were evaluated which had been taken immediately pre- and postoperatively as well as at least six months following surgery and prophylactic irradiation. The functional hip status was evaluated pre- and postoperatively using the Harris Score. Cases in which the Brooker- and/or Harris-Score worsened during the postoperative follow-up as compared to the pre- and immediate postoperative situations were considered as treatment failures. RESULTS: Of 44 patients with at least six months follow-up 41 (93%) experienced a successful prophylaxis. Two failures were observed in the preoperative and one in the postoperative group. The prophylactic efficacy was not influenced if the pre- or postoperative interval was longer than prescribed. All intra- and postoperative complications were comparable for both treatment groups. The mean interval to partial strain (50% body weight) of the operated hip was longer in the preoperative group (mean 19 +/- 27 days) as compared to the postoperative group (mean 8 +/- 13 days). With respect to full strain (100% body weight), the results were equal in both groups. The functional hip status decreased in two patients. Again the mean overall improvement in the postoperative group was larger (mean 42.7 +/- 17.1 points) as compared to the preoperative group (mean 34.3 +/- 13.7 points). CONCLUSIONS: Preoperative and postoperative radiotherapy have equal prophylactic efficacy to prevent heterotopic ossification following hip surgery. The main advantage of preoperative radiotherapy are the simple management of the patient, the reduction of possible complications associated with transport and positioning of the patient in the postoperative period as well as excellent acceptance of this treatment concept by patients, nurses and staff. PMID- 8197552 TI - Consideration of time-dose-patterns in 3D treatment planning. An approach towards 4D treatment planning. AB - PURPOSE: The rendering of the 3D dose distribution together with anatomical information and the volumes of interest (VoI) is essential to get a visual impression of the treatment plan and to find modifications for the optimization of the dose distribution. The integration of biological effects into the 3D treatment planning is of interest for the assessment of different time-dose patterns. MATERIALS AND METHODS: One way of taking into account biological data is to relate the physical dose in critical structures to the corresponding tolerance dose. For that purpose the applied time-dose pattern has to be converted into the standard fractionation scheme being the basis of the tolerance dose. Generally any model can be used for these calculations. Here a modified incomplete repair model is used to calculate the relative biological dose distribution (RBD). The visualization of these biologically isoeffective dose distributions can be performed in the same manner as the physical dose so that the physical and biological dose distributions can by displayed side by side. As this is equivalent to introducing the time as a fourth dimension into 3D treatment planning this is called 4D treatment planning. RESULTS: From 3D dose matrices the biologically isoeffective dose distributions are calculated for the organs at risk. The changes introduced by different time-dose patterns are displayed using the same technique as for rendering 3D treatment plans. The visualisation of the three-dimensional biological dose distributions is shown by means of a patient with an oesophagus carcinoma. The RBD related to the tolerance dose of the organs at risk is displayed for different time-dose fractionations. CONCLUSION: The RBD distribution on a 3D treatment plan can be displayed in the same mode as the physical dose distribution. This offers additionally valuable information in a 3D treatment planning process about the dose to critical organs and the influence of different time-dose patterns. PMID- 8197553 TI - [The radiotherapy of inoperable non-small-cell bronchial carcinoma. A retrospective analysis of 427 cases]. AB - BACKGROUND: The influence of tumor and patient characteristics on survival as well as acute normal tissue toxicity was retrospectively analyzed. PATIENTS AND METHODS: 427 patients with inoperable non-small cell lung cancer were retrospectively analyzed. Two thirds received a total dose of at least 70 Gy, and one third was irradiated with 60 to 66 Gy (2.0 to 2.5 Gy per fraction; split course technique). 92% had a Karnofsky performance index of > or = 80%. Kaplan Meier survival curves were generated and comparisons were made by the log-rank test. Prognostic factors were adjusted for by a proportional hazards analysis. RESULTS: Five-year survival rates (+/- SE) and the median survival times (95% confidence interval) were 2 +/- 2% and 11.1 months (9.1 ... 14.5) after 60 to 66 Gy; 8 +/- 2% and 14.9 months (13.3 ... 16.5) after 70+ Gy. The difference was significant in univariate (p = 0.0013) and multivariate analysis (p = 0.0006). Tumor stage (p = 0.0029: I + II > III; IIIA > IIIB) and gender (p = 0.0387: female > male patients) reached significance in multivariate analysis. Acute pneumonitis and esophagitis were observed in 11% and 9% of cases. CONCLUSIONS: Inoperable non-small cell lung cancer stage I to IIIA should be treated in a curative intention with total doses of about 70 Gy. This is feasible with acceptable normal tissue toxicity. Stage IIIB patients have a particular bad prognosis and should only be treated palliatively. PMID- 8197554 TI - [A final word on the commentary by M. Flentje and M. Wannenmacher regarding our paper: Multisegmental electron irradiation of the chest wall following the ablative therapy of breast cancer]. PMID- 8197555 TI - Breast reconstruction in older women. AB - BACKGROUND: More than 50% of breast cancer care in the United States occurs in women over age 65 years. This study investigates age-related differences in breast reconstruction practices after mastectomy for breast cancer. METHODS: Retrospective review of University of Michigan Breast Care Center patients revealed 242 female patients with breast cancer who underwent postmastectomy breast reconstruction from 1980 through 1991. Data were complied concerning patient age, reconstruction interval (immediate or delayed), type of breast reconstruction performed, reconstruction-associated complications, and the number of postreconstruction procedures required to obtain the final result. Statistical comparisons were made with the chi-squared test. RESULTS: There were 224 patients aged less than 60 years (range 27 to 59 years; median, 44 years) and 18 patients aged 60 years or more (oldest, 68 years). Of the 18 older patients, three underwent delayed transverse rectus abdominus muscle (TRAM) reconstruction; one received a delayed latissimus dorsi flap placed over a silicone gel prosthesis, and 14 underwent 18 reconstructions (4 bilateral) with silicone gel implants (6 immediate, 12 delayed). The younger patients underwent 269 breast reconstructions (45 bilateral), including 92 autogenous tissue reconstructions (34 immediate TRAM, 58 delayed TRAM), 60 immediate and 88 delayed insertions of an expander or prosthesis, and 29 latissimus dorsi flaps with implant reconstructions (3 immediate, 26 delayed). Seven complications (32%) occurred in the 22 breast reconstructions performed in older women, including capsular contracture surrounding an implant (six patients) and a ventral hernia in one patient with a TRAM flap. Complications occurred in 134 breast reconstructions (50%) performed in younger women. All were related to the reconstruction. In the older women a mean of 1.7 +/- 0.7 operations was required to achieve a final reconstruction result versus 2.1 +/- 1.1 in the younger women (not significant). More operations were required in younger women undergoing prosthetic reconstruction than in older women, but this difference was not statistically significant (2.4 +/- 1.2 versus 1.9 +/- 0.7; p = 0.07). Autogenous tissue reconstruction was performed less frequently in older women (14% versus 34%; p < 0.05). No age-related difference was noted in the rate of immediate (versus delayed) reconstruction (27% versus 36%, respectively). Complications occurred more frequently in women who underwent prosthetic breast reconstruction, particularly in younger women (32% in older women and 64% in younger women; p < 0.01). The complication rate for immediate breast reconstruction in older women (all prosthetic) was less than in younger women (17% versus 59%; p < 0.05). For delayed prosthetic reconstructions, complications also occurred less frequently in older than younger women (38% versus 67%; p < 0.05). Between 1988 and 1992, 91 older women and 180 younger women underwent mastectomy for breast cancer; only 7% of older women versus 38% of younger women underwent breast reconstruction (p < 0.001). CONCLUSIONS: Breast reconstruction is a safe option for older women requiring mastectomy. The full array of reconstruction options (autogenous tissue or implants, immediate or delayed) should be considered for use in women of all ages. PMID- 8197556 TI - Transhepatic portal vein stenting for treatment of ruptured duodenopancreatic varices in a patient with chronic pancreatitis. AB - BACKGROUND: Portal vein obstruction with secondary variceal bleeding in the setting of chronic pancreatitis has not been recognized as frequently as splenic vein occlusion. This condition can be difficult to diagnose and treat. METHODS: A 54-year old man was referred for massive recurrent endoscopy-negative upper gastrointestinal bleeding. The diagnosis of duodenopancreatic varices was finally made. Direct portography showed a high-grade stenosis of the proximal portal vein that was dilated and stented with a balloon expandable prosthesis. RESULTS: The gradient across the stenosis fell from 9 to 2 mm Hg. Bleeding stopped. After 7 months of follow-up, the patient has experienced no rebleeding, and a Doppler examination is normal. CONCLUSIONS: In patients with chronic pancreatitis and upper gastrointestinal tract bleeding of unknown origin, obstruction of one of the major splanchnic veins must be excluded. Portal vein dilatation and stenting appears to be a safe procedure with good short-term results. PMID- 8197557 TI - Resection for multiple metastatic liver tumors after portal embolization. AB - BACKGROUND: Five patients with bilateral multiple liver metastases (3 to 12 lesions) from colorectal cancer who underwent extensive liver resection after portal embolization are described. METHODS: Portal embolization of the right portal branch was performed 9 days to 8 months before hepatic resection. The location and number of metastases were determined by intraoperative ultrasonography at the time of liver resection to accomplish complete resection of the tumors. Extended right lobectomy was carried out in four patients, two of whom underwent additional wedge resection of nodules located in the left lateral segment. The other patient underwent right lobectomy associated with local resection of the tumor in the left lobe. RESULTS: The postoperative course in the five patients was uneventful, with no serious complication or liver dysfunction. Although one patient died of recurrence 28 months after liver resection, the remaining four patients were alive and free of cancer between 36 and 74 months after hepatectomy. CONCLUSIONS: The presence of bilateral multiple (four or more) metastatic liver lesions from colorectal cancer is not considered a contraindication for hepatic resection if thorough examination of the liver is performed with intraoperative ultrasonography and the surgical risk is minimal. Portal embolization appears effective for increasing the safety of hepatectomy for patients with small metastases who require major right-sided resection combined with wedge resection of the left lobe. PMID- 8197558 TI - Alterations of pulmonary gas exchange after superimposed carbon monoxide poisoning in acute lung injury. AB - BACKGROUND: Smoke inhalation injury produces substantial morbidity and mortality caused both by immediate catastrophic pulmonary failure and by the subsequent development of pneumonia. Although carbon monoxide (CO) poisoning is present to a degree in nearly all instances of smoke inhalation, the importance of CO in the pathogenesis of smoke inhalation injury remains controversial because smoke contains numerous other potential pulmonary toxins such as aldehydes, chlorine gas, and hydrochloric acid. This study was performed to determine whether CO poisoning acts as a cofactor in the evolution of inhalation injury. METHODS: Four groups of anesthetized dogs received ventilation with 1% CO in room air alone, intratracheal instillation of 2.0 ml/kg 0.1 N hydrochloric acid (HCl) alone, or acid either immediately or 30 minutes before CO. Ventilation/perfusion relationships were measured for 4 hours thereafter with the multiple inert gas elimination technique. RESULTS: Acid instillation established 30 minutes before CO poisoning resulted in significantly decreased carboxyhemoglobin concentrations after ventilation with 1% CO in air for 10 minutes. However, CO elimination was markedly delayed in both acid-challenged groups ventilated with CO. Moreover, acid instillation immediately before CO poisoning significantly exacerbated the development of ventilation/perfusion inequality caused by the acid, because the development of shunt was accelerated. CONCLUSIONS: CO poisoning is an important cofactor in the development of inhalation injury by acceleration of the development of ventilation/perfusion inequality after inhalation. PMID- 8197559 TI - Prognostic factors in surgery for pulmonary metastases in children. AB - BACKGROUND: A retrospective analysis was performed of the results of surgical excision of lung metastases in children to identify prognostic factors. METHODS: From 1970 to 1992, 139 thoracotomies were performed in 91 patients between 1 and 19 years of age with metastases of osteogenic sarcoma (40 patients), nephroblastoma (24 patients), Ewing sarcoma (12 patients), and various other tumors (15 patients). RESULTS: There were no perioperative deaths and only one serious complication, chylothorax necessitating reoperation. Twenty-three patients (25%) are currently alive, two with residual disease. Twelve patients (50%) with nephroblastoma are alive; 7 patients (18%) with osteogenic sarcoma and 4 (27%) with other tumors are alive. Negative prognostic factors were incomplete excision, primary tumor not controlled, or metastases developing during treatment. The number of metastases, the disease-free interval, unilateral versus bilateral metastases, preoperative and postoperative adjuvant treatment, and the number of thoracotomies performed were not of significant influence on outcome. CONCLUSIONS: The most important prognostic factor is the type of primary tumor. Excision of lung metastases in children with Ewing or soft tissue sarcoma is not warranted. All other patients who are able to withstand a major operation should not be denied the chance because the surgical risks appear minimal and the outcome cannot be predicted beforehand. PMID- 8197560 TI - Penetrating trauma to the heart: a relatively innocent injury. AB - BACKGROUND: The purpose of this study was to examine the mortality rate of penetrating cardiac trauma in a large urban hospital. METHODS: This was a retrospective study over a period of 5 years and 5 months of all patients admitted alive with a stab or a gunshot cardiac injury. RESULTS: There were 310 patients with a stab wound and 63 with a gunshot wound. The overall mortality rate was 19%. The mortality rates for the stab and the gunshot groups were 13% and 50.7%, respectively. In the 296 patients with a cardiac stab wound confined to a single chamber and with no other associated extracardiac injury the mortality rate was 8.5%. CONCLUSIONS: An isolated cardiac stab wound is a relatively innocent injury in a patient at a hospital accustomed to managing penetrating trauma expeditiously. PMID- 8197561 TI - Evidence for extraluminal trypsinogen activation in three different models of acute pancreatitis. AB - BACKGROUND: Inappropriate extraluminal activation of trypsin is assumed to play a part in the pathogenesis of acute pancreatitis (AP), but proof has been elusive because active trypsin is transient and difficult to measure. We have previously shown increased levels of trypsinogen activation peptides (TAP), a direct measure of trypsin activation, to correlate with severity of AP, tissue necrosis, and survival in a rodent model induced by cerulein hyperstimulation and bile salt infusion. The present study seeks to show that increased trypsinogen activation also characterizes three other models of experimental AP in rodents to give credence to the generality of the phenomenon and to its potential relevance to human AP. METHODS: Experimental AP was induced in mice by a choline-deficient diet supplemented with ethionine and in rats by creation of a closed duodenal loop or by ligation of the biliopancreatic duct plus physiologic stimulation. TAP were quantified by an immunoassay in tissue and plasma at various time points after onset of AP. RESULTS: In the group with choline-deficient diet supplemented with ethionine a significant increase in tissue and plasma TAP was found at 48 and 72 hours, respectively. In the group with closed duodenal loop significant TAP elevations were found in plasma as early as 6 hours and in the group with ligation of the biliopancreatic duct plus physiologic stimulation at 24 hours. CONCLUSIONS: These experiments provide further evidence that extraluminal protease activation is a pathophysiologic event common to the evolution of various models of experimental acute pancreatitis and therefore increase the likelihood that this phenomenon is important in the human disease as well. PMID- 8197562 TI - Repeat hepatectomy for recurrent hepatocellular carcinoma. AB - BACKGROUND: The significance of repeat hepatectomy for recurrent hepatocellular carcinoma remains controversial. Therefore the aim of this study was to reevaluate both the survival and the surgical risks of repeat hepatectomy. METHODS: The significance of repeat hepatectomy including the survival and the surgical risks for recurrent hepatocellular carcinoma were investigated with 21 patients who underwent a curative repeat hepatectomy during the period between May 1975 and July 1993. For a comparison of survival, 253 patients who underwent a curative primary hepatectomy during the period between April 1985 and July 1993 were used. Moreover, the preoperative liver function tests were also compared between the first and second hepatectomies. RESULTS: Regarding the preoperative liver function tests, the indocyanine green dye excretion rate at 15 minutes in the second hepatectomy (18.7% +/- 8.7%) was significantly higher than that in the first hepatectomy (14.7% +/- 5.9%). With regard to the surgical risks, there was no difference in the clinical parameters for blood loss, operation time, and the incidence of postoperative complications between the first and second hepatectomies. The postoperative hospital stay for the second hepatectomies was relatively shorter than that for the first hepatectomies. In addition, the patient's survival and disease-free survival after a curative repeat hepatectomy were almost identical to that after a curative primary hepatectomy. CONCLUSIONS: A curative repeat hepatectomy is thus considered to be the most effective therapeutic modality for recurrent hepatocellular carcinoma. PMID- 8197563 TI - Randomized controlled trials in surgery. AB - BACKGROUND: The objective was to determine the number of randomized controlled trials (RCT) performed by surgeons, published in surgical journals, or comprising a surgical arm and to assess their characteristics and overall quality. METHODS: RCT in general surgery (including gastrointestinal, breast, surgical oncology, vascular, critical care, and trauma) published in 1990 were retrieved by MEDLINE and analyzed to determine the funding agency, type of therapy, area of surgery, journal published, country of origin, number of centers, and whether a surgeon was the principal author. The completeness of the MEDLINE search was compared to a manual search of the literature. All RCT were assessed with Chalmers' qualitative score. RESULTS: MEDLINE retrieved 202 surgical RCT (46% of those retrieved by a manual search) with a mean score of 0.40 +/- 0.13. However, surgical RCT were performed by surgeons in only one third of trials, compared surgical therapies in only one quarter of trials, and were published in surgical journals in less than one third of trials. Only 22% of surgical RCT were funded by peer reviewed granting agencies. The strongest variables determining the quality of surgical RCT were the type of therapy tested (p = 0.0001), the type of journal published (p = 0.006), and the area of general surgery (p = 0.007). CONCLUSIONS: Although surgical RCT are being performed, there are a relatively low proportion and standard of RCT performed by surgeons as the principal author, published in surgical journals, and comparing surgical therapies. This may reflect a lack of expertise by surgeons in clinical trials, lack of funding for surgical trials, methodologic problems peculiar to surgical trials, or a need for adoption of other research designs to assess surgical therapies. PMID- 8197565 TI - Duke procedure for super obesity: preliminary report with 3.5-year follow-up. AB - BACKGROUND: Super obese patients pose a major health care problem because their obesity is associated with high risks of morbidity and even death. Neither dietary programs nor surgery results in significant or lasting weight loss. Presented here is a new surgical approach, combined with home infusion therapy, that offers effective weight loss with maintenance for 3.5 years. METHODS: Eight super obese patients (252% +/- 19% ideal body weight; 62.7 +/- 5.6 kg/m2 body mass index) underwent near total intestinal bypass anastomosing the proximal 25 to 30 cm of jejunum to the transverse colon. A right atrial catheter was placed for home infusion of necessary fluids, minerals, vitamins, and protein. After desired weight loss was achieved, the jejunocolostomy was taken down with construction of a vertical banded gastroplasty to assist in weight maintenance. RESULTS: An average of 1.5 kg/week was lost. Seven patients lost to an average of 114% +/- 14% ideal body weight (29.0 +/- 2.9 kg/m2 body mass index) after 333 to 556 days. An eighth patient is still losing weight. Weight loss was due mainly to loss of body fat and water. After takedown of the jejunocolostomy and construction of a vertical banded gastroplasty in seven patients, weight loss has been maintained for up to 1218 days. CONCLUSIONS: A new operative approach for super obese patients offers safe and effective weight loss to any desired goal. Subsequent conversion to a vertical banded gastroplasty has so far afforded maintenance of the weight for up to 3.5 years. PMID- 8197564 TI - In vitro release of vasoactive intestinal polypeptide and pancreatic polypeptide from human VIPoma cells and its inhibition by somatostatin analogue (SMS 201 995). AB - BACKGROUND: The purpose of the present study was to determine whether vasoactive intestinal polypeptide (VIP) is released from the tumor cells of VIPoma and if so then to attempt to show how its release is regulated by cultured human VIPoma cells. METHODS: A resected specimen of a pancreatic tumor from a patient with watery diarrhea, hypokalemia, and achrohydria syndrome was examined. The dissociated cells were obtained by collagenase digestion of the tumor tissue and were cultured in vitro. RESULTS: The extraction of tumor cells disclosed that the cells contained VIP and pancreatic polypeptide (PP). Neither insulin, glucagon, somatostatin nor pancreastatin was detected. Immunohistochemically, 40% to 60% of the cells in the tumor stained positively for VIP and 1% to 5% stained positively for PP. The dissociated cells became reaggregated in the culture (50 to 300 microns) and could be maintained in vitro. Incubation experiments revealed a simultaneous in vitro release of VIP and PP with a significant increase by either carbachol or phorbol myristate acetate but not by theophylline or caerulein. Atropine completely abolished the stimulatory effects of carbachol on VIP and PP release. Octreotide (somatostatin analogue [SMS 201-995]) significantly inhibited the carbachol and phorbol myristate acetate-stimulated VIP and PP release. CONCLUSIONS: These findings show the in vitro release of VIP and PP from the VIPoma cells and also provide evidence for the direct inhibitory effect of somatostatin analogue on both the VIP and PP release from the tumor cells. PMID- 8197566 TI - Autologous blood transfusion for hepatectomy in patients with cirrhosis and hepatocellular carcinoma: use of recombinant human erythropoietin. AB - BACKGROUND: We evaluated the benefit of autologous blood transfusion and the effect of recombinant human erythropoietin (rh-EPO) on preoperative autologous blood donation for hepatectomy in patients with cirrhosis. METHODS: Forty-two patients with cirrhosis and hepatocellular carcinoma underwent hepatectomy, 21 of whom (group A) donated autologous blood before operation. Eleven of these patients (group A1) were administered rh-EPO before operation, and ten patients (group A2) were untreated. Twenty-one patients (group B) did not donate autologous blood. RESULTS: The frequency of homologous blood transfusion was 24% in group A and 62% in group B (p < 0.05). Preoperative erythropoiesis increased markedly in group A1, and postoperative erythropoietin production was not suppressed in this group. Postoperative hematocrits recovered significantly more rapidly in patients transfused with only autologous blood. Postoperative serum total bilirubin concentrations were significantly higher in patients with transfused homologous blood. CONCLUSIONS: Autologous blood transfusion yields clinically superior results for hepatectomy in patients with cirrhosis when compared with homologous transfusion. Preoperative rh-EPO administration minimizes presurgical decreases in hematocrit caused by autologous blood donation. PMID- 8197567 TI - Pentoxifylline therapy for chronic claudication: are patients dependent on therapy? AB - BACKGROUND: The purpose of this study was to evaluate the efficacy of long-term pentoxifylline therapy. METHODS: Fifty consecutive patients on long-term pentoxifylline therapy entered a weaning program. The standard dose of 400 mg three times a day was reduced to 400 mg twice a day for 1 month, 400 mg daily for an additional month, and then withdrawn completely for 3 months. Subjective evaluation of each patient's symptoms and objective measurements (treadmill testing for initial claudication distance, maximum walking distance, and ankle/brachial indexes) were evaluated during treatment withdrawal. RESULTS: Twenty-seven patients tolerated withdrawal of therapy without symptomatic deterioration. Seven of nine patients who did not tolerate weaning had deterioration of treadmill ICD/MWD parameters; there was a significant absolute decrease (p = 0.016) in MWD from 430 +/- 78 to 221 +/- 23 feet. Patients with an initial low MWD were less likely to tolerate weaning. Sixty percent of the patients with successful weaning had clinically asymptomatic deterioration of treadmill ICD/MWD parameters. CONCLUSIONS: A substantial number of patients who have been on long-term successful pentoxifylline therapy for claudication can be weaned from the drug. Asymptomatic deterioration of treadmill test parameters is not an indication for resuming therapy. PMID- 8197568 TI - Reconstruction of the hepatic vein to the prosthetic inferior vena cava in right extended hemihepatectomy with ex situ procedure. AB - BACKGROUND: Ex situ procedure permits complete resection of a tumor involving the confluence of the three main hepatic veins, which is difficult when conventional technique is used. METHODS: We report treatment of a patient with intrahepatic cholangiocellular carcinoma involving this confluence of the three main hepatic veins and the retrohepatic inferior vena cava (IVC) by using right extended hemihepatectomy and resection of the retrohepatic IVC with ex situ procedure. Reconstruction of the left hepatic vein required anastomosis of the left hepatic vein and a polytetrafluoroethylene (PTFE) replacement for the IVC. To our knowledge this is the first report of reconstruction of the hepatic vein by use of a PTFE prosthesis. RESULTS: Anastomosis of the left hepatic vein to the PTFE graft was successfully performed during extracorporeal liver operation. The patient has had no recurrence during 8 months since the operation. Neither torsion nor obstruction of the hepatic vein and the graft has been observed. CONCLUSIONS: Reconstruction of main hepatic veins and the PTFE graft as the replacement of the IVC under extracorporeal liver operation may be useful in improving the cure rate and resection rate for liver cancer that is unresectable by the conventional technique. PMID- 8197569 TI - Isolated hepatic caudate lobectomy. AB - BACKGROUND: Isolated caudate lobectomy is a challenging surgical procedure for which safe and reliable techniques have yet to be developed. METHODS: Isolated caudate lobectomy was performed by initial inflow control of the caudate lobe, full mobilization of the liver from the inferior vena cava by dividing all short hepatic veins, and parenchymal division dorsal to the major hepatic veins with a clockwise rotation of the liver while the liver was selectively devascularized by Pringle's maneuver and occlusion of the confluence of the major hepatic veins flush with the inferior vena cava. RESULTS: Two patients with cirrhosis underwent this procedure successfully without intraoperative hemodynamic instability or postoperative liver dysfunction. CONCLUSIONS: This technique allows safe and truly selective excision of the caudate lobe without the need for occlusion of the inferior vena cava or venovenous bypass. PMID- 8197571 TI - Mucinous adenocarcinoma of the colon metastatic to the intestinal mucosa. AB - Autometastasis of colon cancer to the intestinal mucosa is a condition that has not been previously described. The 70-year-old man presented in this case report was seen for routine surveillance colonoscopy 14 months after low anterior resection, without anastomosis, of a Dukes' stage C mucinous adenocarcinoma of the rectosigmoid. The patient had received adjuvant chemotherapy according to Southwest Oncology Group protocol 8899. The routine colonoscopy revealed many new polypoid lesions in the remaining left and transverse colon, and the patient underwent completion total abdominal colectomy. Examination of the specimen revealed more than 100 polyps; the histologic examination identified these polyps as metastatic signet ring mucinous adenocarcinoma. PMID- 8197570 TI - Neuroendocrine ampullary tumors: spectrum of disease including the first report of a neuroendocrine carcinoma of non-small cell type. AB - Primary neuroendocrine tumors of the ampulla of Vater are rare. These tumors, like those of the respiratory tract and remainder of the gastrointestinal tract, appear along a histologic spectrum of increasing malignancy from low-grade carcinoid tumors to high-grade small cell undifferentiated cancers. We herein describe the characteristics of these ampullary neoplasms and report the first case of a neuroendocrine carcinoma of non-small cell type, which represents the middle of this histologic continuum. This tumor seems to follow a more aggressive course than the carcinoid tumor but less aggressive than its small cell counterpart. PMID- 8197573 TI - Support for laparoscopic surgery warning. PMID- 8197572 TI - Recommendations concerning the operative approach for pheochromocytoma invading the inferior vena cava. PMID- 8197574 TI - Blockade of D-1 dopamine receptors in the medial prefrontal cortex produces delayed effects on pre- and postsynaptic indices of dopamine function in the nucleus accumbens. AB - The present experiments assessed the acute and delayed effects of D-1 dopamine (DA) receptor blockade in the medial prefrontal cortex (mPFC) on pre- and postsynaptic indices of DA neurotransmission in the nucleus accumbens (N.Acc). Different groups of rats received intra-mPFC injections of saline (control animals) or the D-1 DA receptor antagonist SCH-23390 (0.25 microgram/side). Acutely, intra-mPFC injections of this antagonist did not affect spontaneous locomotion but significantly increased the locomotion induced by intra-N.Acc. amphetamine (1.5 micrograms/side), in agreement with our earlier findings [Vezina et al. (1991) Eur. J. Neurosci., 3:1001-1007]. When tested two days post injection, however, mPFC-SCH-23390 preexposed animals showed lower levels of locomotor activity than Control animals in response to intra-N.Acc. injections of amphetamine. This effect was not observed in other animals preexposed two days earlier to mPFC injections of amphetamine (2.5 micrograms/side) or the D-2 DA receptor antagonist sulpiride (1.0 microgram/side). Animals preexposed two days earlier to mPFC SCH-23390 also showed higher levels of locomotor activity (+98%) when tested with intra-N.Acc. injections of the D-1 DA receptor agonist SKF-38393 (1.0 microgram/side) and a 36% increase in maximal DA-sensitive adenylate cyclase activity in comparison to Control animals. These effects were no longer observed in animals tested seven days following the mPFC SCH-23390 injections. These results demonstrate delayed actions resulting from cortical D-1 DA receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8197575 TI - MK-801 prevents the development of behavioral sensitization during repeated morphine administration. AB - Acute administration of morphine (10 mg/kg) to rats elicited an increase in locomotion that became sensitized upon repeated treatment over 14 days. Administration of the noncompetitive N-methyl-D-aspartate receptor (NMDA) antagonist MK-801 (0.1 or 0.25 mg/kg) prior to each morphine injection prevented the development of behavioral sensitization to morphine, an effect that persisted even after a 7-day withdrawal from repeated treatment. Sensitization was also prevented by coadministration of the competitive NMDA receptor antagonist CGS 19755 (10 mg/kg). In contrast, acute pretreatment with MK-801 did not alter the response of sensitized rats to morphine challenge, indicating that MK-801 does not prevent the expression of sensitization. When administered alone, MK-801 produced stereotyped movements at moderate doses (0.25 mg/kg) and horizontal locomotion at higher doses (0.5 mg/kg). Repeated administration of 0.25 mg/kg MK 801 elicited sensitization to its own locomotor stimulatory effects, such that this dose became capable of eliciting horizontal locomotion. Sensitization was not seen during repeated administration of 0.1 mg/kg MK-801 or 10 mg/kg CGS 19755, although both of these pretreatments did produce a sensitized response to subsequent challenge with 0.25 mg/kg MK-801. This effect was enhanced by coadministration of morphine, even though repeated administration of morphine alone failed to sensitize rats to MK-801 challenge. These results suggest a complex interplay between NMDA and opioid receptors, such that NMDA antagonists prevent morphine sensitization while morphine enhances the ability of NMDA antagonists to elicit sensitization to their own locomotor stimulatory effects. PMID- 8197576 TI - Divergence of hippocampal mossy fibers. AB - By connecting the fascia dentata with the hippocampus proper, the axons of the granule cells, the mossy fibers, represent an important element of the main excitatory, trisynaptic pathway of the hippocampal formation. In this review the various synaptic connections of the mossy fibers are discussed. It turns out that the mossy fibers do not only establish synapses with the pyramidal neurons of regio inferior as traditionally assumed, but a variety of local circuit neurons as well as projection cells are also contacted by the mossy fibers. Thus there is an underestimated divergence of the impulse flow within the "trisynaptic" pathway at the level of the mossy fibers. Similarly, the pattern of afferent input to the granule cells, especially that of GABAergic neurons, is more complex than previously assumed. In this respect the concept of a unidirectional "trisynaptic" pathway certainly is an oversimplification. In particular, the hilus of the fascia dentata, that the mossy fibers traverse on their way to regio inferior, is often neglected in this concept. The hilar region comprises a large variety of morphologically and functionally distinct neuronal types that, to a large extent, are targets of hilar mossy fiber collaterals. By focusing on the mossy fiber system, an attempt is made in this review to summarize new data on hippocampal circuitries that have been accumulated since the original description of the trisynaptic pathway. This concept, which originally comprised the synapses of the perforant path fibers on dentate granule cells, the mossy fiber synapses on CA3 pyramidal neurons, and the synapses of the Schaffer collaterals on CA1 pyramidal cells, has been of great heuristic value but needs to be modified in view of recent morphological and physiological data. PMID- 8197577 TI - Gene expression in central cholinergic neurons in response to axotomy and deafferentation. AB - Although the molecular and cellular responses to injury in the central nervous system (CNS) have been widely investigated, few studies have examined the potential variations between direct and indirect neuronal injury. To differentiate between the response to axotomy and deafferentation, two central cholinergic populations were analyzed: the horizontal limb of the diagonal band of Broca (HLDB) and the interneurons in the corpus striatum (CS). At time points from one hour to eight weeks postinjury the levels of choline acetyltransferase (ChAT) mRNA and protein were assessed by in situ hybridization and immunohistochemistry. Also examined was the expression of the immediate early gene product, c-fos. One week post axotomy, neurons in the HLDB exhibited an increase in the levels of ChAT mRNA without a concomitant increase in ChAT protein, followed by a steady decrease reaching a nadir in both parameters at eight weeks. In contrast, a transient increase occurred at one week postdeafferentation in the levels of both ChAT mRNA and protein in the interneurons of the CS. Axotomized neurons in the HLDB did not exhibit either c fos mRNA or protein expression, while robust fos induction occurred after one hour in deafferented neurons in the CS. These data demonstrate that the molecular and cellular responses differ following direct and indirect neuronal injury. Furthermore, they suggest that in these central cholinergic populations deafferentation may result in cellular hyperactivity and cell survival while axotomy results in decreased cellular activity and subsequent cellular regression. PMID- 8197578 TI - PET study of [11C]beta-CIT binding to monoamine transporters in the monkey and human brain. AB - The cocaine congener beta-CIT has been labeled with 11C for positron emission tomographic (PET) studies of the dopamine transporter. In the present autoradiographic study on human brain sections and PET study on monkey and human [11C]beta-CIT accumulated markedly in the striatum. [11C]beta-CIT binding in the striatum was selective to the dopamine transporter. The binding in the thalamus was on an intermediate level and was displaced by compounds having affinity for norepinephrine and serotonin transporters. The neocortical binding was on a low level and could be displaced only by citalopram, a serotonin uptake inhibitor. A high dose of cocaine intravenously (7 mg/kg) induced a 50% occupancy of specific [11C]beta-CIT binding to the dopamine transporter in the striatum. This dose is much higher than the doses of 0.25-0.5 mg/kg i.v. for cocaine arousal in human subjects. The finding indicates that cocaine arousal may be induced at a low dopamine transporter occupancy of a few percent. [11C]beta-CIT should be a useful radioligand to explore cocaine actions in humans and to follow the pathophysiological process in vivo by PET in neurodegenerative diseases of the striatum. PMID- 8197579 TI - Identification and characterization of striatal cell subtypes using in vivo intracellular recording in rats: I. Basic physiology and response to corticostriatal fiber stimulation. AB - The electrophysiological characteristics of two subtypes of striatal neurons, identified by their distinct patterns of response to paired impulse stimulation of corticostriatal afferents, were compared using in vivo intracellular recordings in rats. As observed in previous extracellular recording studies, the majority of neurons (73%) were found to be of the Type II class, with the remaining cells exhibiting the Type I response pattern. For all cells, cortical stimulation elicited 5-30 mV EPSPs at latencies ranging from 2.0-5.3 msec. Increasing the stimulating current intensity caused a progressive increase in the amplitude of the evoked EPSPs without altering their latencies, suggesting that the EPSPs are monosynaptically mediated. Both the average amplitude and duration of the evoked EPSPs at spike threshold in Type I neurons (9.8 +/- 1.7 mV, 11.8 +/ 2.8 msec; mean +/- SEM) were significantly smaller than those of Type II cells (20.3 +/- 1.4 mV, 22.7 +/- 2.1 msec). Although the average latency to the onset of the EPSP was similar for both cell classes (Type I cells: 2.3 +/- 0.3 msec; Type II cells: 2.2 +/- 0.2 msec), the EPSPs in Type I cells reached peak amplitude and the spikes were triggered at significantly longer latencies than in the Type II cells (peak I: 11.2 +/- 2.5 msec vs. II: 7.6 +/- 0.7 msec; spike I: 8.0 +/- 1.2 msec vs. II: 5.7 +/- 0.4 msec). Striatal neurons had a comparatively hyperpolarized resting membrane potential (-70.2 +/- 2.1 mV) and had an average input resistance of 35.4 +/- 7.6 M omega. Overall, striatal neurons exhibited low levels of spontaneous activity (0.6 +/- 0.7 Hz) with 50% of the neurons being quiescent. Type I cells exhibited significantly higher firing rates (3.2 +/- 0.8 Hz) than Type II cells (0.8 +/- 0.3 Hz), although their resting membrane potentials were not significantly different. Spontaneously occurring spikes had an average amplitude of 72.7 +/- 3.4 mV and spike thresholds of -50.1 +/- 1.5 mV. Irregularly occurring depolarizing plateau potentials, which typically gave rise to spike discharge, were frequently observed in both spontaneously firing and quiescent neurons. A small proportion of the cells recorded (3/55) exhibited a Type I response pattern but had unique physiological characteristics that were similar to those described by others as arising from large, aspiny striatal neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8197580 TI - Buprenorphine and morphine produce equivalent increases in extracellular single unit activity of dopamine neurons in the ventral tegmental area in vivo. AB - Buprenorphine is a synthetic opioid proposed as a potential treatment for drug abuse. Although buprenorphine is widely considered to be a partial agonist at opioid receptors, little is known of its electrophysiological effects in the central nervous system. Because buprenorphine has been reported to have limited hedonic effects in humans, and since activation of the dopaminergic system is thought to be critical to the reinforcing effects of drugs, we compared the ability of buprenorphine and morphine to activate dopamine neurons. We report here that buprenorphine and morphine are equally effective in increasing the impulse flow of dopamine cells in the ventral tegmental area. Extracellular single unit activity was recorded from dopaminergic (DA) neurons in the ventral tegmental area (VTA) of chloral hydrate anesthetized rats. Standard physiological and anatomical criteria were used to identify DA neurons. Systemic injection of buprenorphine (5-200 micrograms/kg, i.v.) and morphine (1-10 mg/kg, i.v.) produced equal magnitudes of activation in a similar subset of DA neurons in the VTA (buprenorphine: 173%; morphine: 164%). Unlike morphine, the activation by buprenorphine was not reversed by the opioid antagonist naloxone (50-100 micrograms/kg, i.v.), but this is consistent with the known pharmacodynamics of buprenorphine at opioid receptors. These studies demonstrate that acute administration of buprenorphine has morphine-like effects on the impulse activity of DA neurons. The implications for use of buprenorphine as a clinical treatment for drug abuse are discussed. PMID- 8197581 TI - Mercuric chloride and p-chloromercuriphenylsulfonate exert a biphasic effect on the binding of the stimulant [3H]methylphenidate to the dopamine transporter. AB - Mercuric chloride was found to have a biphasic effect on the binding of the radiolabeled stimulant [3H]methylphenidate to membranes from a crude synaptosomal preparation of rat striatal tissue. Binding was enhanced at low concentrations of HgCl2, reaching a maximum of 62% above control values at 2.5 microM HgCl2. It was inhibited in a dose-dependent manner at concentrations greater than 5 microM HgCl2, with an IC50 of 7.2 microM. The increase in binding observed at the low concentrations of HgCl2 was shown by Scatchard analysis to be due to an increase in the affinity of [3H]methylphenidate for its binding site on the dopamine transporter, while a decrease in both affinity and Bmax accompanied the reduction of [3H]methylphenidate binding observed at the higher concentrations of the inorganic mercury compound. The sodium salt of the organic mercurial p chloromercuriphenylsulfonic acid also caused an increase in [3H]methylphenidate binding (159% above controls at 2,000 microM), followed by an immediate decrease in binding at higher concentrations of the reagent. Because both of these mercury containing compounds have a high propensity for interacting with sulfhydryl groups, these data suggest that the cysteine residues in the dopamine transporter molecule may play an important role in the regulation of stimulant binding to the uptake complex. PMID- 8197582 TI - Identification and characterization of striatal cell subtypes using in vivo intracellular recording in rats: II. Membrane factors underlying paired-pulse response profiles. AB - Two subtypes of neurons in the striatum have been defined on the basis of their different response patterns to paired-impulse stimulation of corticostriatal afferents, with type I cells showing a longer spike latency, facilitation at short intervals, and inhibition at long intervals, and type II cells defined by the facilitation occurring at long interstimulus intervals. Nevertheless, the companion report has shown that this distinction of cell types cannot be accounted for by differences in the basic physiological properties of these cells, but instead is likely to be due to differences in their synaptic connectivity. The experiments performed in this study were directed at examining in detail the membrane factors and synaptic responses that may contribute to these distinct response patterns. When pairs of stimuli were delivered to the corticostriatal fibers at 10-30 ms interstimulus intervals, the EPSPs elicited in type I neurons exhibited a temporal summation, resulting in a facilitation of spike firing to the second stimulus relative to the first. In contrast, type II cells showed decreased EPSP amplitude at short intervals, and in cells showing a short-interval inhibition, there was a significant increase in spike threshold (+5.3 +/- 1.4 mV) during the second response. All type II neurons recorded with KCl-filled microelectrodes showed short-interval facilitation with little or no change in spike threshold. Although the use of KCl electrodes did not alter the facilitation at short intervals in type I neurons it did increase the rate of rise of the EPSP, causing spikes to be triggered at a latency similar to that of type II cells. Paired stimuli delivered at 75-150 ms interstimulus intervals showed inverse effects on type I and type II cells with respect to the probability of spike firing. In type I cells, the evoked EPSP was followed by a long-latency membrane hyperpolarization that prevented the second EPSP from reaching spike threshold. In contrast, the smaller-amplitude hyperpolarization evoked in type II cells enabled the second stimulus to activate an EPSP at the same membrane potential as the first stimulus, resulting in a facilitation of spiking.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8197583 TI - Effects of supplemental choline on extracellular acetylcholine in the nucleus accumbens during normal behavior and pharmacological acetylcholine depletion. AB - Brain microdialysis was used to determine whether systemic or local application of choline would modify the extracellular concentration of acetylcholine (ACh) in the nucleus accumbens (NAc) of freely moving rats. Supplemental choline given intraperitoneally or into the NAc of normal rats did not increase extracellular ACh. When local ACh interneurons in the NAc were treated pharmacologically to deplete the intracellular stores of ACh, then systemic choline (80 mg/kg) was an effective treatment. Specifically, 1) blockade of the high-affinity choline transporter with hemicholinium-3 (HC-3) to reduce ACh synthesis caused a decrease in extracellular ACh, but choline supplementation restored ACh toward its normal level in the NAc. 2) Local bicuculline treatment released ACh to the point of depletion, but systemic choline or locally infused choline helped maintain normal ACh levels. These results suggest that choline supplementation might be useful in preventing depletion of ACh in the nucleus accumbens during pathological conditions. PMID- 8197584 TI - Identification and characterization of striatal cell subtypes using in vivo intracellular recording and dye-labeling in rats: III. Morphological correlates and compartmental localization. AB - In the first two reports of this series, in vivo intracellular recording techniques were used to characterize the electrophysiological properties of two types of striatal neurons that had been identified by their distinct response patterns to stimulation of corticostriatal afferents. In this paper, we examined whether cells showing Type I or Type II response patterns also differed with respect to their morphology or compartmental localization by combining intracellular recording and Lucifer yellow staining with immunocytochemical localization of calbindin 28 kd immunoreactivity. In the majority of cases, both Type I and Type II neurons exhibited similar morphological characteristics, with 80% of the Type I cells (13/16) and all of the Type II cells (n = 40) being small or medium spiny neurons. In each case where the morphological class of the cell was different than the spiny cell class, the cell exhibited a Type I response pattern. These spiny neurons had somata that averaged 17.1 +/- 1.3 microns in diameter and gave rise to between four and eight primary dendrites. The axons typically arose from cell bodies (7/13 for Type I and 25/40 for Type II cells) and emitted extensive local axonal collaterals. However, the axons of Type I cells more frequently originated from the dorsal surface of the somata (9/13; 69%), whereas Type II axons more frequently arose from the ventral surface of the somata (25/35; 71%), which may account for their different extracellular waveforms. In coronally sectioned tissue (n = 18), the axons always projected laterally when the somata were located in the medial striatum and projected medially when the somata were in the lateral striatal region. In a subset of experiments (N = 22), Lucifer yellow-stained neurons were localized with respect to their position within the patch and matrix compartments of the striatum using subsequent staining for calbindin 28 kd immunoreactivity. Of the 20 labeled medium spiny neurons examined (Type II: N = 13; Type I: N = 7), 19 were located in the calbindin-positive matrix compartment. The only neuron localized to the patch compartment was a medium spiny cell that exhibited a Type II paired impulse response pattern. In addition, of the two aspiny neurons from this group with beaded dendrites, one was localized to the border between adjacent patch and matrix compartments, whereas the other was located completely within the matrix compartment. Therefore, despite their distinct paired impulse response patterns, the majority of both Type I and Type II neurons were medium spiny cells located in the matrix compartment of the striatum.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8197585 TI - [Displacement and resection of the ascending colon in the horse: a literature review on the basis of 2 cases]. AB - A review of displacements and surgery of the large colon is given on the basis of two cases. A four-year-old Dutch Warmblood mare was referred, one week before foaling, for colic of twelve hours duration. At rectal palpation a large uterus was found, but no cause for the colic. Laparotomy revealed a colonic volvulus and resection of about 75% of the large colon was necessary. A dead foal was born five days postoperatively, but the mare recovered well. A nine year-old Dutch Warmblood stallion with a history of frequent colic had been treated for nephrosplenic entrapment three times. Resection of the left part of the colon was performed successfully to prevent another entrapment. PMID- 8197586 TI - [Toon Wilderbeek, general director Intervet International. 'Utrecht is not the center of the world'.. Interview by Sophie Deleu]. PMID- 8197587 TI - Effect of superoxide dismutase and catalase on the nephrotoxicity induced by subchronical administration of ochratoxin A in rats. AB - Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus ochraceus as well as other molds. It is a natural contaminant of mouldy food and feed. OTA has a number of toxic effects, the most prominent being nephrotoxicity. Furthermore, OTA is immunosuppressive, genotoxic, teratogenic and carcinogenic. OTA inhibits protein synthesis by competition with phenylalanine in the phenylalanine-tRNA aminoacylation reaction. Recently, lipid peroxidation induced by OTA has been reported, indicating that the lesions induced by this mycotoxin could be also related to oxidative pathways. It was then interesting to study effects of the superoxide dismutase (SOD) and catalase on the nephrotoxicity induced by OTA in rats. The two enzymes (20 mg/kg body weight each) were given to rats by subcutaneous injection, every 48 h, 1 h before gavage by OTA (289 micrograms/kg b.w. every 48 h), for 3 weeks. SOD and catalase prevented most of the nephrotoxic effects induced by ochratoxin A, observed as enzymuria, proteinuria, creatinemia and increased urinary excretion of OTA. Altogether these results indicate (i) that superoxide radicals and hydrogen peroxide are likely to be involved in the damaging processes of OTA in vivo, (ii) that SOD and catalase might be used for prevention of renal lesions in cases of ochratoxicosis. PMID- 8197588 TI - Effect of bolesatine, a glycoprotein from Boletus satanas, on rat thymus in vivo. AB - Bolesatine is a glycoprotein purified to homogeneity from Boletus satanas Lenz, a toxic mushroom which causes serious gastroenteritis. This lectin possesses a mitogenic activity on human lymphocytes at very low concentrations, whereas higher concentrations inhibit protein synthesis in vitro in several systems. The mitogenic activity on peripheral blood T lymphocytes in vitro has been shown to be at least 200-fold higher than the activity of the well studied phytohemagglutinin (PHA). In order to verify this property in vivo, the effect of bolesatine has been studied in thymus of rats given orally bolesatine. Two groups of bolesatine-treated animals were used in addition to the control group. One group was given every 48 h, 28 micrograms of bolesatine/kg body weight seven times and 150 micrograms/kg body weight 48 h before the sacrifice. The other group was given 55 micrograms of bolesatine/kg body weight according to the same protocol and 150 micrograms/kg body weight 48 h before the sacrifice. In these conditions, the ratio thymus weight/body weight is increased by 10% and 28%, respectively, in groups 1 and 2. Similarly, the DNA synthesis is increased by more than 50%, indicating that (i) bolesatine probably possesses a mitogenic effect on thymocytes in vivo (ii) that the increase of the ratio thymus weight/body weight is not due to swelling by water retention, but rather to a multiplication of thymocytes. These results are confirmed in a second run of experiments in which bolesatine given orally to rats in lower doses of 3-12 micrograms/kg induces an increase of both thymus weight by 47% to 54% and an increase of total proteins by 52% to 56%, respectively, whereas the ratio total protein/g of thymus does not change. Thus bolesatine, known to be mitogenic to human lymphocytes in vitro is also mitogenic to rat thymocytes in vivo. PMID- 8197589 TI - Effects of menthofuran, a monoterpene furan on rat liver microsomal enzymes, in vivo. AB - Oral administration (250 mg/kg) of menthofuran, a monoterpene furan, to rats once daily for 3 days caused hepatotoxicity as judged by a significant increase in serum glutamate pyruvate transaminase (SGPT) and decreases in glucose-6 phosphatase and aminopyrine N-demethylase activities. Administration of menthofuran also resulted in a decrease in the levels of liver microsomal cytochrome P-450, whereas cytochrome b5 and NAD(P)H-cytochrome c reductase activities were not affected. These effects of menthofuran were both dose- and time-dependent. Pretreatment of rats with phenobarbital (PB) prior to menthofuran treatment potentiated hepatotoxicity suggesting that a PB-induced cytochrome P 450 catalyzed the formation of reactive metabolite(s) responsible for the hepatotoxicity. PMID- 8197590 TI - Cyanide-induced lipid peroxidation in different organs: subcellular distribution and hydroperoxide generation in neuronal cells. AB - To evaluate hydroperoxide generation as a potential mechanism of cyanide neurotoxicity, mice were treated with KCN (7 mg/kg, subcutaneously (s.c.)) and the level of lipid peroxidation (expressed as conjugated dienes) was measured later in various organs. Brain showed elevated conjugated diene levels after cyanide but the liver, which is not considered a target for cyanide toxicity, showed no increase. The heart also showed no increase, whereas kidney conjugated dienes slowly increased to a peak 1 h after cyanide. In vitro studies show elevation of peroxidized lipids in mouse brain cortical slices following incubation with KCN (0.1 mM). Omission of calcium from the medium or pretreatment of brain slices with diltiazem (a calcium channel blocker) prevented formation of conjugated dienes by KCN. Calcium thus appears to play a critical role in cyanide induced generation of peroxidized lipids in neuronal cells. Subcellular fractionation of brains from mice treated with cyanide showed that lipid peroxidation increased in the microsomal fraction but not in the mitochondrial fraction. Fluorescent studies using 2,7-dichlorofluorescein (a hydroperoxide sensitive fluorescent dye) show that hydroperoxides are generated rapidly after cyanide treatment of PC12 cells, a neuron-like cell, and hydroperoxide levels remain elevated for many minutes in the presence of cyanide. These results suggest that hydroperoxide generation with subsequent peroxidation of lipids may lead to changes in structure and function of certain membranes and contribute to the neurotoxic damage produced by cyanide. PMID- 8197591 TI - Long-term effects of Aroclor 1254 (PCBs) on plasma lipid and carnitine concentrations in rhesus monkey. AB - Sixty-seven female rhesus monkeys (Macaca mulatta) were orally dosed daily for 152 weeks with 0, 5, 20, 40, and 80 micrograms Aroclor 1254 (PCB)/kg body wt. Blood polychlorinated biphenyl (PCB) concentrations were highly positively correlated (r = 0.92, P < 0.001) with doses of PCB administered. A comprehensive analysis of plasma lipids/lipoproteins revealed a PCB-associated increase in plasma triglycerides and decreases in plasma total cholesterol, high-density lipoprotein cholesterol (HDL-chol), very-low plus low-density lipoprotein cholesterol (VLDL+LDL-chol), and total carnitine (which is involved in fatty acid metabolism). All of the lipid/lipoprotein changes were significantly (P < or = 0.05) correlated with blood PCB concentration. These data, obtained after 152 weeks of continuous daily exposure of a primate model to PCB support a causal relationship between plasma lipid changes and PCB intake. Previously, causality has been refuted on the premise that the commonly observed elevation of triglycerides with increasing concentration of blood PCB is a reflection, not of PCB dose, but of the partitioning of PCB between tissues (adipose) and blood in proportion to the blood lipid present. The mechanism of the plasma lipid changes was not investigated in this study but the altered lipid/lipoprotein pattern is discussed with respect to known cardiovascular risk profiles. PMID- 8197592 TI - The susceptibility of spontaneously diabetic mice to cadmium-metallothionein nephrotoxicity. AB - Cadmium metallothionein (CdMT) was injected subcutaneously into obese hyperglycaemic Umea ob/ob mice or their lean litter mates (normal mice) at doses of 0, 0.1 and 0.4 mg Cd/kg. Proteinuria and calciuria were induced in both types of mice, but in the ob/ob mice this condition developed at a lower dose of CdMT (0.1 mg Cd/kg) than in the normal mice (0.4 mg Cd/kg). These results show, therefore, that Umea ob/ob mice are particularly susceptible to CdMT-induced nephrotoxicity. The mechanism underlying this phenomenon needs to be further investigated. After the administration of CdMT, a dose-related increase in glycosuria was observed in both types of mice, in spite of decreased levels of serum insulin and glucose. It is suggested that such glycosuria induced by CdMT could be one of the signs of cadmium nephrotoxicity. The results of the present study thus indicate that metabolic changes like those in diabetes may increase susceptibility to cadmium-induced renal tubular damage. PMID- 8197593 TI - Effect of chelate treatments on kidney, bone and brain lead levels of lead intoxicated mice. AB - The effects of chelating agent treatment with meso-2,3-dimercaptosuccinic acid (DMSA), Na2CaEDTA, Na2ZnEDTA, and Na3ZnDTPA on the organ lead levels of lead loaded mice have been determined. At 1 mmol/kg/day i.p., all caused reductions in the lead levels of the kidney after four injections, but only Na2CaEDTA produced a significant reduction in brain lead. All chelating agents caused significant reductions in kidney and brain lead levels when administered at a daily dose of 1 mmol/kg/day for eight days, but only DMSA reduced the bone lead level. In animals given 50 mg Pb/kg or 100 mg Pb/kg, the administration of Na2CaEDTA or DMSA at 1 mmol/kg/day x 8 produced significant reductions in kidney, bone and brain lead levels, but DMSA produced greater reductions of bone lead in both groups and of kidney lead in the group given 100 mg Pb/kg. An examination of published data describing the effect of chelating agent treatment on brain lead levels indicates that DMSA produces a reduction in brain lead levels under all conditions examined to date. PMID- 8197594 TI - [Do the elderly remain of account?]. PMID- 8197595 TI - [Body weight of elderly patients on admission to a nursing home]. AB - Body weight of elderly patients on admission to a 'verpleeghuis' (Nursing-home in the Netherlands) was 5 to 8 kg lower than that of healthy persons of the same age living at home. No difference in body weight was found between 'verpleeghuis' patients on admission and after long stay. Psychogeriatric men weighed more than somatic; the body weight of psychogeriatric and somatic women did not differ. Terminal patients weighed less than chronic patients and patients, who could be discharged from the 'verpleeghuis'. A relationship was found between body weight and age: the older the patient is, the lower he weighs. Body weight of women was also lower in the case of 'unmarried status' and 'admission residential homes'. PMID- 8197596 TI - [Pressure sores in a psychiatric hospital: a report of 10 years of systematic decubitus treatment]. AB - Ten years of systematic treatment of pressure sores in a general psychiatric hospital (1983-1992) are reported on. Most of the patients were aged 65 years or older. The prevalence of pressure sores among them varied between 1.4 and 3.8%, whilst among younger patients the prevalence varied between 0 and 0.8%. Over the reported ten years the seriousness of the wounds decreased and prognoses improved. The percentage of healed patients increased from 56 in 1983 to round about 80 in the last few years. Over the years the number of patients with new pressure sores showed a varying course. PMID- 8197597 TI - [Structure of the Behavior Observation Scale-Geriatrics]. AB - The GOS-G is a rating scale for describing the behaviour of demented elderly, old psychiatric inpatients and non-degenerative organic psychiatric patients. The scale lacked a reliable grouping of the 34 items. Therefore a factor analysis was performed on 205 patients belonging to the aforementioned groups (mean age = 69.6 y). The analysis resulted in nine dimensions (explained variance = 67.8%): Mobility, Social activity, Aggressive and suspicious behaviour, Cognition, ADL, Psychotic behaviour, Disoriented behaviour, Restless at night, and Depressive and anxious behaviour. The internal consistency measure alpha (N = 205) and the test retest reliability (N = 34; interval 1 month) of the total scale were both .87 each. The internal consistency of the subscales varied from .60 to .86 and the stability from .42 to .93. The GOS-G-behavioursubscales differentiated significantly between demented elderly, old psychiatric inpatients and patients with non-degenerative organic dysfunctions. PMID- 8197598 TI - [Digit series and Knox cubes as concentration tests for elderly subjects]. AB - We studied psychometric properties of the Digit Span test and its nonverbal counterpart, the Knox Cube test, with reference to their utility in the clinical assessment of the elderly. Subjects were 100 residents of residential homes and semi-independent housing projects, aged 68 to 94. An administration of Digit Span with three trials per sequence length provides high reliability and minimizes floor effects, allowing separate interpretation of the Forward and Backward conditions. Due to its low internal consistency, the Knox Cube test cannot reliably distinguish differences among normal subjects, but may still be useful to detect impairment. Using regression equations, the Forward Digit Span score can be corrected for education level and both Digit Backward and Knox Cubes can be compared with Digit Span Forward. PMID- 8197599 TI - Secondary malignancies after marrow transplantation for leukemia or aplastic anemia. PMID- 8197600 TI - Nondepleting anti-CD4 antibodies in transplantation. Evidence that modulation is far less effective than prolonged CD4 blockade. AB - CD4+ T cells are obvious targets for immunotherapy since they appear to be pivotal in rejection responses. Current interest in clinical transplantation is focused on the potential use of nondepleting anti-CD4 antibodies largely because depletion of CD4+ T cells may lead to prolonged periods of nonspecific immunosuppression. We have examined the efficacy of two nondepleting antibodies, KT6 and YTS 177.9, in a mouse cardiac allograft model. KT6 causes abrupt and prolonged occupation of CD4 molecules in vivo, while YTS 177.9 results in rapid and almost complete modulation of CD4 from the cell surface. In identical perioperative two-dose protocols, equivalent doses of KT6 were more effective than YTS 177.9 (MST 58 days and 24 days, respectively). When the treatment protocols were redesigned to include one or two additional doses of antibody, given as CD4 molecules were either released from blockade (KT6) or re-expressed following modulation (YTS177.9), the YTS 177.9 protocol led only to a slight improvement in graft survival (MST 51 days), whereas the modified KT6 regimen gave indefinite survival in 100% of the recipients. These data clearly show that modulating anti-CD4 antibodies may be far less effective than antibodies that effect prolonged CD4 occupation, a significant observation especially in relation to the proposed clinical use of the antibody OKT4A, which appears to cause modulation rather than CD4 blockade. PMID- 8197601 TI - The lack of interaction between transplanted human fetal pancreas and liver. AB - Trophism between transplanted hepatocytes and pancreatic endocrine tissue has been demonstrated with both adult and late gestational fetal tissue. Since this effect has not been looked for with fetal tissue obtained early in pregnancy, we conducted a series of experiments transplanting human liver and pancreas, which was obtained early in the second trimester (15-20 weeks gestation), beneath the renal capsule of athymic mice. Fetal pancreatic explants increased in size after transplantation into nondiabetic mice, but their insulin content 11 weeks later was not different from that of grafts that included liver explants. Reversal of diabetes was achieved in 2 of 5 diabetic mice transplanted with pancreas alone, but none of the mice that received pancreas and liver became normoglycemic. Histological examination of grafted liver explants, which consist of hepatocytes and hematopoietic cells, showed that hepatocytes survived for only two weeks regardless of the presence of pancreatic explants. Bile ducts differentiated by this time in both groups and were still present at 7 weeks. In conclusion, there was no trophic effect observed between transplanted fetal human liver and pancreatic endocrine tissue obtained early in pregnancy; bile duct differentiation is a feature of fetal human liver xenografted into the athymic mouse. PMID- 8197602 TI - Tolerance of porcine renal allografts induced by donor spleen cells and seven days' treatment with cyclosporine. AB - Liver allografts in pigs and in rats elicit a substantial cellular immune response that can resolve spontaneously with the induction of donor-specific systemic tolerance. Self-limiting interactions between host and donor (graft) derived leukocytes may be the basis for tolerogenesis. We have attempted to reproduce this effect of liver grafting in pigs by peroperative infusion of donor leukocytes into kidney graft recipients given an interrupted short course of CsA designed to promote donor leukocyte survival and interaction with host cells. This protocol can secure long-term kidney graft survival resistant to challenge by donor skin grafting. Donor skin is, however, rejected, but more slowly than third-party skin, indicating a degree of systemic specific unresponsiveness in these long-term kidney graft recipients. PMID- 8197604 TI - Rat liver blood flow after ischemia and reperfusion. The effects of the platelet activating factor antagonist WEB-2170 and of removing circulating leukocytes. AB - The inflammatory response to trauma induces release of platelet activating factor (PAF), which promotes leukocyte adherence to the vascular endothelium. Ischemia and reperfusion induces inflammatory reactions that play a role in reperfusion injury, and here we investigate the role of both PAF and of leukocytes in damage to reperfused rat liver. The experimental procedure consisted of the temporary interruption of blood flow to the left lateral and medial lobes of the rat liver in vivo, and subsequent reperfusion after defined periods. Rats were pretreated either with the PAF-antagonist WEB-2170 or with vinblastine to induce leukopenia, and compared with controls. The postischemic liver blood flow and liver oxyhemoglobin saturation were recorded using an He-Ne Laser doppler flowmeter and photometer. Reperfusion after 30 and 45 min of ischemia was associated with partial recovery to normal values and was inversely proportional to the duration of ischemia. In the WEB-2170-treated group, liver flow and hemoglobin saturation upon reperfusion did not show significant differences when compared with the untreated control groups, suggesting that inhibition of PAF activity did not protect against the microcirculatory disturbance induced by ischemia and reperfusion in the liver. In contrast, rats made leukopenic by treatment with vinblastine showed significantly better recovery of blood flow and hemoglobin saturation than the control group after 45 min of ischemia. Thus, we found that although PAF alone did not appear to have a pivotal role in the cascade of reperfusion injury, the effect of leukocytes is critical. PMID- 8197603 TI - Modulation of the release of cytokines and reduction of the shock syndrome induced by anti-CD3 monoclonal antibody in mice by interleukin-10. AB - Since IL-10 was recently shown to inhibit several T cell functions in vitro, we investigated the effects of IL-10 on the cytokine release syndrome induced in mice by the 145-2C11 anti-CD3 mAb. As OKT3 in man, this mAb induces a massive polyclonal T cell activation before to induce immunosuppression. First, we found that administration of 1000 U of recombinant mouse IL-10 (mIL-10) 30 min before injection of 10 micrograms of the 145-2C11 antimouse CD3 mAb markedly reduced the systemic release of IFN-gamma and TNF. In contrast, IL-10 pretreatment did not significantly modify the release of IL-6. To determine the effect of IL-10 pretreatment on the endogenous secretion of IL-10 induced by the 145-2C11 mAb, mice were injected with human IL-10 (hIL-10) which does not cross-react in the ELISA for mIL-10 determination. While hIL-10 was as efficient as mIL-10 in reducing TNF and IFN-gamma release, it did not modify peak serum levels of IL-10. The modulation of cytokine production by mIL-10 was associated with a significant reduction of the toxicity of the 145-2C11 mAb, as assessed by the attenuation of hypothermia and by the reduced lethality in D-galactosamine-sensitize mice. We conclude that IL-10 differentially regulates the in vivo production of cytokines and decreases the systemic toxicity induced by the 145-2C11 mAb. These observations suggest potential therapeutic applications of IL-10 in organ transplantation, especially in association with anti-CD3 mAb. PMID- 8197605 TI - Determination of blood flow to the transplanted kidney. A novel application of phase-contrast, cine magnetic resonance imaging. AB - There is at present no noninvasive method that reliably measures blood flow in the poorly functioning renal allograft. The present study was designed to evaluate phase-contrast cine magnetic resonance imaging (PC-cine-MRI) for this purpose. We recruited for study 18 patients who had received kidney transplants 13-66 months earlier from closely related living donors. As judged by the glomerular filtration rate, which was elevated for a single kidney (76 +/- 4 ml/min 1.73 m2), allograft function was excellent, permitting the assumption of unimpaired renal extraction of paminohippuric acid (PAH). Allograft blood flow was determined consecutively on the same day, first by the standard PAH clearance technique and they by the product of the velocity of protons and renal vein cross sectional area using PC-cine-MRI. MRI determinations could not be completed because of claustrophobia in two patients and failure to image the terminus of the allograft vein another two. Comparison of blood flow in the remaining 14 subjects revealed the two techniques to be strongly related (r = 0.91, P < 0.001). On the average, the renal blood flow rate was similar by each method; 732 +/- 62 by PAH clearance and 703 +/- 69 ml/min by PC-cine-MRI, but the agreement among individuals between the two methods was only modest, with a 95% confidence interval of agreement from -214 to +254 ml/min. We conclude that PC-cine-MRI provides a fairly accurate and noninvasive method for determining the rate of blood flow in the transplanted kidney. With further refinement it should permit the role of depressed blood flow in a variety of acute and chronic forms of human allograft dysfunction to be elucidated in humans for the first time. PMID- 8197606 TI - The hyperfiltration hypothesis in human renal transplantation. AB - The hyperfiltration hypothesis postulates that kidneys with reduced renal mass will progress toward failure due to hypertrophy of the remaining nephron to meet the excess load, eventually leading to nephron exhaustion. Five conditions in which hyperfiltration might be suspected were studied in human kidney transplantation: (1) small kidneys from donors aged 4 to 6; (2) transplants into large recipients (over 100 kg); (3) grafts from females to males compared with males to females; (4) kidneys that experience rejection episodes; and (5) cadaveric grafts compared with living-unrelated donor grafts. In all 5 instances, the requirement for dialysis and discharge serum creatinine level were both high- and, correspondingly, the 1- and 3-year graft survival rates were lower than the controls. The discharge SCr was the best indicator of 1-3-year graft survival and may serve to measure the "fit" of the kidney to the recipient--for even in patients requiring no dialysis graft survival was related to the discharge SCr levels. One consequence of this hypothesis is that many late graft losses currently attributed to rejections may, in fact, be hyperfiltration failures. As evidence, a progressively higher incidence of reported late rejections was noted even in patients who had been rejection-free at the time of discharge if they had higher discharge SCr values. We conclude that the 5 conditions under which hyperfiltration damage might be suspected had increased failure rates. Such failures are almost never reported as "due to hyperfiltration" and are probably recorded as rejections. PMID- 8197607 TI - An evaluation of vesical urodynamics before renal transplantation and its effect on renal allograft function and survival. AB - This prospective study investigated the urodynamics of the urinary bladder prior to renal transplantation in 57 patients and related this to graft function and transplantation outcome. The study demonstrated a clear deterioration in the pretransplant urodynamic characteristics in all subgroups, with male patients in the hemodialysis group (HD) showing a more substantial decline: 1st sensation volume (ml) in male HD patients = 112 (120) vs. 171 (173) in male CAPD patients, P < 0.05; and corresponding average flow rate for same groups 3 (3) ml/sec vs. 5 (5) ml/sec, P < 0.05. Figures are median (interquartile range). We have identified a subgroup of patients with a small bladder capacity (less than 100 ml) who have a reduced graft survival (55% vs. 92% for bladders larger than 100 ml at 2 years) apparently unrelated to immunological processes. PMID- 8197608 TI - Systemic chimerism in sex-mismatched liver transplant recipients detected by fluorescence in situ hybridization. AB - Fluorescent in situ hybridization (FISH) is a reliable, rapid, sensitive, and quantitative method for detection of residual host cells following sex-mismatched bone marrow transplantation. Recently, donor-derived long-term multilineage hematopoiesis was detected in a sex-mismatched liver transplant recipient. We therefore assessed chimeric status in 12 patients (F 9, M3), mean age 42.5 years (range 16-57), for a median period of 18 months (range 7-32) following sex mismatched liver transplantation. Peripheral blood hematolymphoid cells were hybridized with Y- or X-chromosome fluorescently labeled specific probes, and the donor-typed hematopoietic cells were enumerated. In two F recipients 4-5% male hematolymphoid cells were detected in the peripheral blood at 15 and 22 months after sex-mismatched liver transplantation, respectively. These two patients with systemic chimerism suffered from primary biliary cirrhosis and fulminant Wilson's disease before transplantation. One of them had evidence of graft rejection only once during the posttransplant course and the other had no episode of graft rejection. Two other female patients who were found to have approximately 2% male hematolymphoid cells, which is considered to be in the false-positive range, also had no signs of graft rejection during the posttransplant follow-up period. Among the remaining eight patients, in whom systemic chimerism was undetectable, there was at least one episode of acute cellular rejection during the posttransplant period. In summary, the FISH technique enables us to detect systemic chimerism following sex-mismatched liver allografts. Inasmuch as balanced systemic chimerism after organ transplantation is of major importance for self tolerance, our findings may enable us to treat patients after liver transplantation without the need for immunosuppression. PMID- 8197609 TI - Screening donors for xenotransplantation. The potential for xenozoonoses. AB - Xenotransplantation is a potential solution to the current donor shortage for solid organ transplantation. The transmission of infectious agents from donor organs or bone marrow to the recipient is a well-recognized phenomenon following allotransplantation. Thus the prospect of xenotransplantation raises the issue of xenozoonoses--i.e., the transmission of animal infections to the human host. Anticipating an increasing number of baboon to human transplants, 31 adult male baboons (Papio cynocephalus) from a single colony in the United States were screened for the presence of antibody to microbial agents (principally viral) that may pose a significant risk of infection. Antibody to simian cytomegalovirus, simian agent 8 and Epstein-Barr virus, was found in 97% of animals tested. Antibody to simian retroviruses and Toxoplasma gondii was found in 30% and 32% respectively. Discordant results were found when paired samples were examined by two primate laboratories. This was particularly noted when methodologies were based on cross-reaction with human viral antigens. These results highlight the need to develop specific antibody tests against the species used for xenotransplantation. PMID- 8197610 TI - Prediction by a modified mixed leukocyte reaction assay of graft-versus-host disease and graft rejection after allogeneic bone marrow transplantation. AB - In this report we describe a modified, sensitive MLR test that appears to detect fine antigenic disparities between HLA-identical siblings confirmed as such by serology and the standard MLR test. In a group of 40 consecutive allogeneic bone marrow transplants, reactivity detected by the modified MLR test correlated with the development of rejection of matched marrow grafts and onset of acute graft vs. host disease (aGVHD). Thus, 13/15 positively reacting patient/donor pairs developed one of these complications (P < 0.001), while only 2/25 developed aGVHD in the negatively reacting group. This test may be useful for selecting the most compatible donor when several potential donors are available. PMID- 8197611 TI - Relation of cyclosporine blood levels to adverse effects on lipoproteins. AB - Hyperlipidemia is common in renal allograft recipients. To elucidate the role of cyclosporine in posttransplant hyperlipidemia, we measured lipids, lipoprotein lipids, and apolipoproteins of thirty-five renal allograft recipients and evaluated their relation to trough cyclosporine blood levels. All patients were on a triple immunosuppressive regimen with equal doses of prednisone and azathioprine, and had stable graft function. Cyclosporine blood levels were significantly correlated to total plasma cholesterol (P = 0.028), low-density lipoprotein cholesterol (P = 0.022), apolipoprotein B (P = 0.017), and the cholesterol/high-density lipoprotein cholesterol ratio (P < 0.002), but not to plasma triglycerides. Significant inverse correlations were found between cyclosporine blood levels and high-density lipoprotein cholesterol (P = 0.034), high-density lipoprotein3 cholesterol (P = 0.025), and apolipoprotein A-1 (P = 0.047), but not high-density lipoprotein2 cholesterol. The independent relation of cyclosporine blood levels to each of the measured lipid parameters was investigated by a stepwise regression model including age, body mass index, interval from transplantation, diabetes mellitus, plasma creatinine, and intake of diuretics and beta-blockers. After correction for these 7 variables, cyclosporine blood levels remained significantly associated with high-density lipoprotein cholesterol, high-density lipoprotein3 cholesterol, apolipoprotein A 1, apolipoprotein B, low-density lipoprotein cholesterol, and the cholesterol/high-density lipoprotein cholesterol ratio. These data suggest that cyclosporine causes atherogenic dyslipidemia. PMID- 8197612 TI - Weight-independent dosing of cyclosporine--an alternative to the "mg/kg" doctrine. AB - Cyclosporine is usually prescribed as "mg CsA per kg body weight", and blood levels are used for guiding CsA therapy. The present study evaluated whether it is sensible to dose in "mg/kg" if one wishes to obtain specific CsA blood levels. In a retrospective analysis, 1071 consecutive CsA whole-blood trough levels from 164 renal transplant patients, measured by monoclonal parent RIA, were correlated with the respective oral CsA doses and several demographic parameters, including gender, age, weight, height, and time after transplantation. From this, we derived a concept of "weight-independent CsA dosing" which was prospectively tested in three series of patients during the first days after renal transplantation: 58 patients received 2x 100 mg/day CsA from day 0 with the intention to reach target levels of 40-80 ng/ml, 42 patients received 2x 200 mg/day CsA from day 4 (target: 100-200 ng/ml), and 38 patients received 2x 300 mg/day from day 4 (target: 100-200 ng/ml). In the retrospective analysis, the individual, patient-specific relation of CsA level to CsA dose (in mg) was found to depend only on height (P = 0.02) and time after transplantation (P < 0.001), but not on body weight (b. wt.). If the CsA dose was expressed in "mg/kg", patients < or = 55 kg b. wt. required nearly twice the doses of patients > or = 75 kg b. wt., whereas the mean CsA requirement was the same when expressed in "mg".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8197613 TI - Extended preservation of the liver with UW solution--is it justifiable? AB - The outcome of 228 liver grafts in 208 elective adult recipients was assessed to identify any adverse effects of extending the length of cold preservation with UW solution beyond 12 hr. A total of 114 grafts had been preserved < 12 hr--median 9.5 (group I) and 114 > 12 hr--median 14.5 (group II). Intraoperative blood and blood product usage, graft function, hospital stay, and graft and patient survival were identical in the two groups. Biliary strictures occurred in 5.7% of grafts (8 anastomotic (3 group I, 5 group II; 5 hilar/nonanastomotic: 3 group I, 2 group II). There was no graft or patient loss due to the hilar strictures but 1 patient died following reconstruction of an anastomotic stricture (0.4%). It is concluded that extending the cold preservation to approximately 15 hr does not adversely affect outcome after liver transplantation. PMID- 8197614 TI - Adenovirus-mediated gene transfer in the transplant setting. I. Conditions for expression of transferred genes in cold-preserved hepatocytes. AB - Transplantation of genetically modified hepatocytes has been suggested as a therapeutic modality for impaired hepatocellular function. This study examined adenoviral-mediated gene transfer to isolated hepatocytes, under conditions mimicking clinical transplant preservation. Isolated rat hepatocytes were infected using replication-defective adenoviral vectors with an expression cassette containing the beta-galactosidase gene driven by a CMV promoter. Hepatocytes were infected in suspension immediately after isolation, then either cultured or transplanted immediately into a syngeneic host. Gene transfer efficiency was assessed by histochemical staining and FACS analysis for the gene product. The presence of viral DNA and mRNA, as well as viral-derived protein production, were assayed. Efficiency of gene transfer was examined as a function of several preservation conditions. Infection efficiency was best in cells preserved in UW solution, correlated directly with virus:hepatocyte ratio and with length of exposure to virus. Successful infection resulted in significant viral-derived protein production, persisting for at least two weeks in culture. These results demonstrate the versatility of adenoviral vectors in accomplishing rapid and efficient gene transfer into nondividing hepatocytes during cold preservation. Such genetically modified hepatocytes have potential use for immediate transplantation, without the need for further manipulation. PMID- 8197615 TI - Adenovirus-mediated gene transfer in the transplant setting. II. Successful expression of transferred cDNA in syngeneic liver grafts. AB - These experiments establish a model for gene transfer to transplanted liver grafts ex vivo using adenoviral vectors. Rat liver grafts (n = 8) were harvested, and preserved in UW or lactated Ringer's. The grafts were infected ex-vivo via portal vein perfusion with replication-defective Ad vectors encoding the beta galactosidase (beta-gal) gene diluted in UW solution. The infected grafts were stored at 4 degrees C for 1 hr, then transplanted into syngeneic hosts. Liver biopsies were taken at 1, 7, and 15 days after transplantation. Infection rate was assessed by histochemical staining for beta-gal. Liver DNA and RNA were assayed for the beta-gal sequences, and recombinant protein production measured at 24 hr and 7 days after transplantation. Under conditions mimicking liver graft cold storage, efficient gene transfer was achieved with an infection rate of 10 15%, as assessed by X-gal staining. Viral DNA and RNA presence in the graft was confirmed; gene expression with protein production were verified by western blots and a functional protein assay. All studies were negative in control livers. Gene expression persisted for at least 2 weeks after transplantation. We conclude that efficient adenovirus-mediated gene insertion and expression of gene products can be accomplished in whole-liver grafts under hypothermic preservation conditions currently used in clinical transplantation. PMID- 8197616 TI - Evidence of alloreactive T suppressor cells in the maintenance phase of spontaneous tolerance after orthotopic liver transplantation in the rat. AB - In the DA-->PVG rat strain combination liver allografts are spontaneously tolerated and induce a state of systemic tolerance towards donor antigens. Thirty long-term (> 100 days)-surviving liver recipients in this strain combination were used to study humoral and cellular mechanisms of tolerance in the maintenance phase after liver transplantation. In the popliteal lymph node assay splenocytes of liver grafted or native PVG rats displayed a similar proliferative response in (DAxPVG)F1 hybrid rats, indicating an unaffected capacity of these cells to mount graft-versus-host reactions. Using adoptive transfer assays T-splenocytes (1x10(7) cells, MRC Ox 19+, MRC Ox12-, CD 5) of long-term-surviving liver recipients were able to suppress the rejection of DA hearts (donor-specific), of DA and AO kidney grafts in irradiated (300 cGy) PVG recipients. Serum of long term-surviving liver recipients was able to suppress the rejection of semiallogeneic (DAxPVG)F1 heart grafts after double injection of 1 ml serum, while fully allogeneic DA heart as well as skin and pancreaticoduodenal grafts were resistant to passive enhancement. The results confirm the development of spontaneous tolerance after liver grafting in the DA-->PVG strain combination, and the demonstration of T cells with suppressive capacity in adoptive transfer experiments indicates a role for T suppressor cells in the maintenance phase of spontaneous tolerance after liver grafting. PMID- 8197617 TI - The effect of cyclosporine on calcium, protein kinase C, and sodium-proton exchange in platelets. AB - Cyclosporine increases platelet aggregation as well as the risk of thromboembolism. To test the hypothesis that CsA stimulates platelets by activating cytosolic calcium [Ca2+]i and related mechanisms, we measured the effects of CsA on [Ca2+]i, protein kinase C (PKC), and sodium/proton (Na+/H+) exchange. [Ca2+]i was measured in human platelets with fura 2, PKC was determined by the phosphorylation of the endogenous 47 kDa protein, and Na+/H+ exchange was measured with BCECF after acidification of the platelets with propionic acid. CsA alone did not influence basal PKC activity in platelets. However, CsA augmented the thrombin-induced phosphorylation of the specific PKC substrate p47 in platelets in a dose-dependent fashion. CsA did not affect basal [Ca2+]i--however, it increased thrombin-induced calcium influx. The effect of CsA on PKC was not dependent on the CsA-induced calcium influx. CsA increased Na+/H+ exchange, which was blocked completely by a PKC inhibitor. Our results demonstrate that CsA directly augments PKC-dependent cellular mechanisms in platelets. PMID- 8197618 TI - Posttransplant bladder recovery--a prospective randomized trial of two techniques of ureteric anastomosis. PMID- 8197619 TI - Expression of donor and recipient class I MHC antigens by Kupffer cells after orthotopic rat liver transplantation. An immunoelectron microscopic study. PMID- 8197620 TI - A new xenogeneic radiation chimera (hamster-to-rat). PMID- 8197621 TI - Collagenase distension, two-step sequential filtration, and histopaque gradient purification for consistent isolation of pure pancreatic islets from the market age (6-month-old) pig. PMID- 8197622 TI - Analysis of ultrasonographic prostate images for the detection of prostatic carcinoma: the automated urologic diagnostic expert system. AB - This paper describes a study on the automated analysis of ultrasonographic prostate images. With image processing, tissue characterization in the prostate was performed to assess the probability of malignancy. During prostate examinations, images were recorded at the positions where biopsies were taken. The used samples were divided into three groups. Two of them were used for the construction of a classification tree, and the third was used for the evaluation of this classification. A sensitivity of 80.6% and specificity of 77.1% were reached retrospectively. In a prospective way, these results were 80.0% and 88.2%, respectively. The prospective predictive value for cancer detection was 85.7%. The presented prospective value for image analysis was almost twice as high as the values normally found for prostate examination. PMID- 8197623 TI - The geometrical relationship between the human esophagus and left ventricle: implications for three-dimensional ultrasonic scanning. AB - To establish design parameters for a transesophageal ultrasonic probe to image the left ventricle (LV) in three dimensions, the geometrical relationship between the esophagus and the heart was studied in computed tomographic sections of ten humans. Points describing the esophageal centerpoint and the left-ventricular endocardium were digitized. Algorithms were developed to determine from any esophageal viewpoint the ranges of motion required to cover the LV with four modes of scanning; transverse oblique, longitudinal oblique, rotary and linear. Longitudinal oblique scanning was the only single-degree-of-freedom method that allowed complete imaging of the LV in all patients. However, for both conventional and three-dimensional LV imaging, the most promising probe design appears to be a rotary scanning probe with an added degree of freedom to tilt the axis of rotation +/- 29 degrees away from an axis perpendicular to the local esophageal axis. PMID- 8197624 TI - Ultrasonic imaging of the stress distribution in elastic media due to an external compressor. AB - We describe an experimental ultrasonic method capable of imaging the two dimensional distribution of longitudinal stress in an elastic, tissue-like material due to an external compressor of arbitrary size or shape and boundary conditions. The method involves the use of a compressor and an opposing ultrasonic transducer. Local strains are derived from the ultrasonic backscatter signals before and after compression using cross correlation analysis. The strain distribution is converted to a stress map by assuming a linear stress-strain relationship. The technique is useful for quantifying the corrections that must be made to images of the elastic modulus of tissue (elastograms) due to the effects of compressor size and shape, depth and boundary conditions. It is also useful for experimental modeling of stress distributions in elastic media. PMID- 8197625 TI - Effect of sample window length on the correlation between RF signal and pulsed Doppler signal intensity. AB - Ultrasound pulsed Doppler systems, as used in medical applications, are based on the detection of the phase difference between a reference signal and the received radio frequency (RF) signal averaged over the sample window. Thereby, it is implicitly assumed that the phase of the received signal will increase linearly with depth. However, the ultrasound signal originates from particles with a random spatial distribution. Therefore, it may be anticipated that the accuracy of the estimate for the phase difference will not improve by elongating the sample window. To test this hypothesis, simulated random phase RF signals with various bandwidths were subjected to demodulation using a rectangular observation window of different lengths. It is concluded that the correlation coefficient between RF intensity and Doppler intensity goes down for long sample windows. Moreover, the coefficient of variation of the estimate for the intensity of the received signal decreases for an increasing length of the observation window. The variation coefficient of the Doppler amplitude remains very close to one for all signal and processing conditions. These observations demonstrate that for Doppler signal amplitude assessment, the effect of the length of the observation window should be taken into account. PMID- 8197626 TI - An evaluation of overlying tissues to determine fetal exposure to ultrasound during the third trimester. AB - Measurements of minimum and average total tissue thicknesses overlying the fetus during the third trimester were taken on 52 patients between 24 and 40 weeks gestation. Minimum total thickness of tissues constantly along the ultrasound path had a mean value of 1.75 cm, ranging from 0.40 to 3.70 cm. This corresponded to a mean attenuation of 0.87 dB MHz-1, ranging from 0.30 to 1.68 dB MHz-1. Average total thickness of tissues constantly along the ultrasound path had a mean value of 2.16 cm, ranging from 1.00 to 4.10 cm. This corresponded to a mean attenuation of 1.16 dB MHz-1, ranging from 0.64 to 2.03 dB MHz-1. Average attenuation was also calculated for all soft tissues along the ultrasound path, including the placenta. The resulting average attenuation was 0.47 dB cm-1 MHz-1. Maternal weight at the time of ultrasound examination had significant correlation with minimum and average ultrasound attenuation by tissues constantly along the ultrasound path. The R2 value was 46.7% for minimum attenuation (p-value < 0.0001) and 53.3% for average attenuation (p-value < 0.0001). Multiple regression analyses showed that the model that included maternal weight, pregnancy weight and fetal gestational age was a better predictor of the amount of attenuation during the third trimester than the model that included maternal weight only. The R2 value of the model that included all three variables was 57.2% (p-value < 0.0001) for minimum attenuation, and 62.4% (p-value < 0.0001) for average attenuation. PMID- 8197628 TI - Ultrasound-induced lung hemorrhage in the monkey. AB - Studies with the mouse have shown that lung hemorrhage can result from exposure to ultrasound at a peak pressure of approximately 1 MPa at 4 MHz (Mechanical Index [MI] approximately 0.5). In order to determine whether a comparable outcome could occur in a larger animal with characteristics similar to humans, studies were performed with monkeys using a clinical scanner under maximum output conditions (imaging + pulsed and color Doppler; derated pr of 3.7 MPa [4.5 MPa, measured in water], 4 MHz; MI approximately 1.8) (N = 57). Monkeys ranged in age from 1 day of life to 16 years with exposures limited to the right lung lobes (5 min cranial, 5 min caudal; N = 41 exposed, N = 12 sham-exposed controls, N = 4 colony controls). Results showed that animals ranging in age from 3 months to 5 years (mean age of 2.5 years) had a greater propensity for the occurrence of multiple well-demarcated circular hemorrhagic foci (0.1-1.0 cm), which were not observed in either control group. These lesions were characterized by marked congestion of alveolar capillaries with accumulation of red blood cells within the alveolar spaces, and were unassociated with major vessels or respiratory bronchioles. Further studies will be required in order to determine the relevance of these findings to the human, although it was concluded that ultrasound-induced lung hemorrhage in the monkey is of a significantly lesser degree when compared to the mouse. PMID- 8197627 TI - Effects of pulsed ultrasound on the mouse neonate: hind limb paralysis and lung hemorrhage. AB - Exposure conditions were determined for hind limb paralysis and lung hemorrhage of neonatal mice due to pulsed exposure (10 microsecond pulse duration) to 1 MHz focused ultrasound. Spatial peak pulse average intensity and peak rarefactional pressure levels for paralysis in 50% of specimens sonicated were determined for pulse repetition frequencies of 1, 5 and 50 kHz at 10 degrees C and 2.4 s exposure duration. The results suggest that cavitation was involved in the paralysis at a pulse repetition frequency (PRF) of 50 kHz, but that cavitation took place in the coupling medium and probably not within the specimen during exposures at a PRF of 5 kHz. The results show an inverse relation between spatial peak pulse average intensity, or peak rarefactional pressure and sound on-time. Exposure conditions for lung hemorrhage were determined for a pulse duration of 10 microseconds at 10 degrees C and exposure durations of 2.4 and 180 s. The results show that the threshold exposure conditions for lung hemorrhage are much less than the conditions for cavitational or other effects reported for tissues that do not contain well defined gas bodies. In addition, the results show an inverse relation between exposure level and either exposure duration or sound on time, suggesting that time is an important parameter associated with bubble effects. PMID- 8197629 TI - Calcium and the effects of ultrasound on frog skin. AB - Therapeutic ultrasound is used to enhance the repair of soft tissue, muscle, etc., and because many of the cellular reactions involved in these processes are dependent on the intracellular availability of free calcium ions, it becomes important to study the effects of ultrasound in the presence and the absence of calcium ions. Using frog skin as a biological model, the effect of therapeutic ultrasound (300 mW/cm2 1 MHz CW) was investigated. Sonication for two minutes caused a significantly larger increase in total ionic conductance (Gt) in the presence of calcium ions (140% vs. 27%). However, the time constant for Gt to return to steady state was significantly longer in calcium-free solutions (122 vs. 18 min.). This study demonstrates that the biological effects of ultrasound are influenced by calcium ions. Furthermore, the recovery time constants confirm recent findings regarding the function of calcium ions in the formation of tight junctions. The role of free radicals produced by cavitation and calcium potentiated lipid and protein peroxidation is discussed. PMID- 8197630 TI - Development of standard measurement methods for essential properties of ultrasound therapy equipment. AB - In a European collaborative project, partly funded by the EC Community Bureau of Reference (BCR), reliable methods of measurement for characterising the output and performance of ultrasound physiotherapy equipment have been developed. Experimental investigations using miniature hydrophones to scan the distribution of pressure in therapeutic fields have been undertaken in combination with theoretical simulations of the sound fields. Important parameters such as Beam Cross Sectional Area (BCSA), Effective Radiating Area (ERA) and Beam Nonuniformity Ratio (BNR) (characterising "Hot-spots": potentially harmful to patients) have been redefined, and these new definitions have been incorporated in a revision of IEC 150:1963. The reproducibility and accuracy of measurements of ERA based on these procedures are presented in detail for a variety of therapy fields. Furthermore, it is shown that the value of the BNR for any treatment head should not exceed 8. Values of effective intensity derived using the new procedures are shown to be significantly higher than those obtained using FDA (USA) definitions, a conclusion in agreement with the theoretical expectations. Measurements on four treatment heads were used to validate the procedures of the proposed revised standard. Values of ERA derived by the two laboratories were in agreement to within 2.5%. PMID- 8197631 TI - [Combination of Monteggia and Galeazzi injury of the same arm]. AB - A combination injury to the forearm, consisting of Monteggia- and Galeazzi lesion is described. After osteosyntheses of the fractures the dislocation of the head of radius and ulna were reduced spontaneously because of restauration of correct axes and length. Because of a simultaneous fracture of the coronoid process an above elbow plaster cast was supplied. Healing took place with free motion of all joints. PMID- 8197632 TI - [Prosthesis of the head of the radius in long-term follow-up--vitallium versus silastic]. AB - At the Graz Hospital for Accident Surgery, seven Vitallium prostheses were implanted in the period from 1964 to 1968, and nine Silastic prostheses in the period from 1984 to 1991. In January 1993 we were able to do control examinations in eleven patients. Five of them with fractures of type B2.3, five of B3.3 and one of C3.3 according to the AO-Classification. Secondary treatment was done in four patients by prosthetic substitution. All patients had to wear a cast postoperatively for two to eight weeks. Our results--like those already described in relevant literature--clearly confirm the markedly poorere outcome of secondary treatment by prosthetic substitution of the head of the radius. On the basis of our results we therefore recommend in all cases where resection seems to be unavoidable to perform primary atraumatic resection with complete removal of all bone splinters and subsequent prosthetic substitution of the head of radius, if it is not possible to an osteoynthetic operation without immobilisation. We did not find any correlation to the classivication of the fracture types. PMID- 8197633 TI - [Public health requirements within the scope of quality assurance in ambulatory surgery. Status: 8 October 1993]. PMID- 8197634 TI - [Imaging of alloplastic ligament implant. An in vivo and in vitro study exemplified by Kevlar]. AB - Neither native X-ray nor CT or NMR allow to evaluate intraarticular implantation results of Kevlar -49 directly. In animal trials, the course of an artificial ligament may only be presumed from connective tissue ingrowth. Although soft tissue structure appears much better in NMR than in CT, direct proof of ligament continuity is still impossible. As soon as the connective tissue becomes continuous, it appears clearly and allows indirect evaluation of the prosthesis, as integrity can be judged by its shape like in natural cruciate ligament. Anatomic preparations show that connective tissue fills up the small space between the two cords of a Kevlar -49 two bundle prosthesis eight weeks after implantation, so that imaging systems show only one intraarticular bundle. PMID- 8197635 TI - [Standardized ultrasound examination for classification of instability of the acromioclavicular joint]. AB - Anteroposterior X-ray views of both acromio-clavicular (AC-) joints with 10 kg weights in each hand are generally accepted for the diagnosis of Tossy I to III AC-joint separations. An analogue diagnosis can be made by standardized ultrasound examination. Ten individuals without AC-instability (Tossy I), eleven with Tossy II- and eight with Tossy III-instability were examined both radiographically and by B-mode ultrasound. AC-joint width was uniformly calculated by using an index (AC-index = AC-joint width of uninjured side/AC joint width of injured side). The sonographically measured mean AC-index for Tossy I-stability was 1.0; sonographically 0.49 and radiographically measured 0.5 for Tossy II-injury; and sonographically 0.21 and radiographically measured 0.2 for Tossy III-instability. Statistical analysis resulted in significant differences for all mean AC-indices of the three groups (p < 0.0001). We conclude that ultrasound examination of AC-joint instability is as reliable as radiographic measurement. Standard X-rays of the shoulder remain mandatory to exclude fractures only. The decision for operative stabilisation of the AC-joint can be based on the side-effect free and cost-effective ultrasound examination of the grade of AC-joint instability (AC-index < 0.3 equivalent Tossy III). PMID- 8197636 TI - [Results of surgical management of unstable pertrochanteric femoral fractures with the dynamic hip screw and T-plate]. AB - The dynamic hip screw (DHS) is a widely used method of osteosynthesis. Nevertheless, supplying instable pertrochanteric fractures is problematic because the gliding screw may cause a considerable dislocation of fragments in lateral direction. Is there any alternative method disposable, bearing stability of DHS- osteosynthesis can be improved by adding a lateral T-plate. We reached full bearing stability in four cases. PMID- 8197637 TI - [Results of implantation of uncemented porous metal hip prostheses]. AB - 72 patients having cementless spongy-metal hip prosthesis were reexamined by clinical and radiological check up two to seven years after implantation (average 43 months). In case of five patients hip prosthesis had to be changed due to loosening (no bony ingrowth n = 2, loosening of acetabular component due to technical faults n = 3). In correlation to clinical results 88% could be considered as excellent or good, 9% acceptable and 3% as inadequate. 10% of the patients complained about thigh pain. The typical radiological bony reactions of the surrounding bone are described. An evaluation of the radiological results can only be done under consideration of the clinical problems involved. In view of the positive results obtained in the recent time the use of spongy-metal hip prosthesis can be recommended for cementless hip joint replacement in case of younger patients. Especially in case of cemented hip joints which have become loose it will be an advantage to use spongy-metal hip prosthesis. PMID- 8197638 TI - [Fractures of the proximal tibia and knee ligament injuries]. AB - The risk of secondary osteoarthritis after proximal tibial fractures is influenced by the reconstruction of both the articular surface and associated knee ligament injuries. In a follow-up of 69 operatively treated tibial head fractures 36.2% revealed ligamentous damages. At high risk were young male patients with fractures of the medial or both tibial condyles. Only 33% of the ligament damages were the cause of fracture dislocations as described by Moore. Avulsion fractures of the knee ligaments can be successfully treated on by primary fixation. For ruptures of the medial collateral ligament a functional therapy is often sufficient whereas damages of the cruciate ligaments need secondary reconstruction. PMID- 8197639 TI - [Local antiseptics in surgery--rebirth and advances]. AB - The history of antisepsis is marked by names such as Pringle, Lister, Billroth, Koch, Kocher, von Volkmann, von Nussbaum, Schloffer and Carrel. The revolutionary initial success of Lister's method was followed by severe setbacks because persisting biological intolerance of the chemical and physical antiseptics prevented the main purpose of application: killing bacteria without damaging cells. Until the discovery of penicillin the predominantly used antiseptics were perubalsam (balsamum peruvianum), azo-dyes (Rivanol), and sulphonamides (Cibazol). The dawn of the "antibiotic age" demonstrated once more the limits of locally applied therapeutic effectiveness of these substances (antiseptics, antibiotics) and was often outweighed by the damage caused. For the same reason systemicly applied substances frequently lack satisfactory effectiveness in the area of tissue damage. Experiences with intraoperative and postoperative wound lavage have shown that favourable results achieved by this surgical procedure are more likely due to the mechanical cleaning process than to the effectiveness of the locally applied substances being limited by the restricted duration of influence and the restricted depth of tissue penetration. Taking into account earlier studies and long-term experiences, antiseptic solutions were tested in view of their tissue compatibility, their biologic availability, and their effectiveness in close cooperation of clinic, bacteriology and laboratory medicine. The coordinated investigations resulted in a solution of biguanid (Lavasept) which is free from iodine, quicksilver, PVP and aldehyde. It can be applied for local treatment of wounds liable to infection, as an adjuvant for wound treatment in cases of acute tissue infections, as well as in the surgival practise to take care of acute and chronic infections of soft tissue. Sofar locally applied antiseptics in surgery have proved to be less satisfactory than considered in the course of their history due to side effects, e.g. tissue damage. Coordinated investigations now present an antiseptic solution of biguanid which can be used in various cases of wound treatment to prevent or counteract infections. PMID- 8197640 TI - Non-neurogenic neurogenic nonsense. PMID- 8197641 TI - A no-nonsense reply. PMID- 8197642 TI - In situ extracorporeal shock wave lithotripsy for primary ureteric calculi. AB - OBJECTIVE: To determine the efficacy of the Lithostar lithotriptor for the in situ treatment of primary ureteric stones. METHODS: We reviewed, retrospectively, our experience with 283 patients with primary ureteric stones treated with extracorporeal shock wave lithotripsy (ESWL) using the Lithostar lithotriptor. No attempts were made to manipulate the stones. The majority of the patients were treated using only intravenous analgesia. Auxiliary measures were used in 84 patients (29.6%). There were 112 patients (39.6%) with upper, 53 (18.7%) with middle, and 118 (41.7%) with lower ureteric stones. RESULTS: A single ESWL session was needed for 200 patients (70.6%), two for 49 patients (17.3%), and more than two sessions for 34 patients (12%). Of the 248 patients who had adequate follow-up, 220 (88.7%) were stone free, 14 (5.65%) had some residual stone, while 14 (5.65%) patients failed to respond to the treatment. Patients' gender and body weight influenced the treatment and the clearance rate numerically without any statistical significance. The stone site was the most significant factor influencing the final result. Stones larger than 10 mm and the presence of hydronephrosis adversely affected the treatment. CONCLUSIONS: In situ ESWL of ureteral stones with the Lithostar device is a convenient and efficient method of treating calculi within the whole length of the ureter without the need for any manipulation. PMID- 8197643 TI - Significance of invasion to the muscularis mucosae on the progression of superficial bladder cancer. AB - OBJECTIVE: We tried to determine the significance of invasion to the muscularis mucosae on the progression of superficial bladder cancer. METHODS: We subclassified superficial bladder cancer showing lamina propria invasion into two groups: with (pT1b) or without cancer invasion to or near the muscularis mucosae (pT1a). RESULTS: Of 164 bladder cancers, 76 showed no lamina propria invasion and 88 did. In the tumors with lamina propria invasion, 60 were diagnosed as pT1a and 28 as pT1b. The progression rate of pT1b cancer (53.5%) was significantly higher than that of pT1a cancer (6.7%) (P < 0.01). Regardless of size, number, or grade of tumor, the progression rate of pT1b cancer was significantly higher than that of pT1a cancer (P < 0.01). CONCLUSIONS: We stress that patients with superficial cancer invading to or near the muscularis mucosae should be followed up carefully after transurethral resection. PMID- 8197644 TI - Prostatic fluid analysis in spinal-cord-injured patients with recurrent urinary tract infections. AB - OBJECTIVE: Recurrent urinary tract infections are common in spinal-cord-injured patients. Our study was designed to evaluate the association of bacteria colony counts, white blood cell (WBC) count, and antibody-coated bacteria analyzed in urethral and prostatic samples in hospitalized spinal-cord-injured patients with recurrent urinary tract infections. METHODS: Thirty-three patients were studied and 4 noninfected patients served as controls; 17 patients were paraplegic and 20 were quadriplegic. Mean patient age was 34.8 years and mean follow-up period was ninety-three days. During the surveillance period, 19 of the 33 patients had relapsing infections (same organism), while 14 had reinfections (new organism). A modified Foley catheter was used to seal the bladder neck, so that urethral and prostatic samples could be obtained. RESULTS: Bacteria colony counts and WBC counts did not correlate with relapsing infection. However, significantly more patients with relapsing infection (8/19) had antibody-coated bacteria in their prostatic fluid than patients with reinfection (1/13) (P < 0.05). CONCLUSIONS: The presence of antibody-coated bacteria in prostatic fluid is associated with relapsing urinary tract infections and not with reinfection. PMID- 8197645 TI - Depth of penetration of the neodymium:yttrium-aluminum-garnet laser in the human prostate at various dosimetry. AB - OBJECTIVE: To determine depth of thermal penetration by the neodymium:yttrium aluminum-garnet (Nd:YAG) laser at various dosimetry in the human prostate and to compare results of two techniques of laser application, single spot versus whole tissue photoirradiation. METHODS: Twelve men with Stage T2 (B) cancer of the prostate consented to laser prostatectomy immediately prior to a planned radical prostatectomy. In the first 3 patients (group I) the prostate was treated with the Nd:YAG laser in one spot area of each lobe. The next 9 patients underwent photoirradiation of all endoscopically visible tissues on one side of the prostate at different dosimetries: 60 W at sixty seconds (group II), 50 W at sixty seconds (group III), and 40 W at ninety seconds (group IV). Depth of laser penetration was measured from both histologic and gross evaluations of removed specimens within twenty-four hours. RESULTS: Thermal necrosis in group I showed an inconsistent depth of penetration even with the same amount of laser energy. Groups II, III, and IV all demonstrated clearly demarcated areas of thermal necrosis. Group II showed the greatest depth of laser effect among all groups, with a mean depth of 1.75 cm. No laser effect is detected near the true capsule of the prostate on any specimen. CONCLUSIONS: High dosage laser energy application at 60 W and sixty seconds of pulse duration with the whole tissue treatment provide the greatest depth of penetration in the human prostate while maintaining safety for the capsular area. PMID- 8197646 TI - Homologous blood transfusion in patients with prostate cancer: no effect on tumor progression or survival. AB - OBJECTIVE: To determine the effect of perioperative blood transfusions in patients with prostate cancer who underwent radical prostatectomy, we analyzed 1,785 patients with a follow-up of five years or more who were treated during a twenty-one-year period (1966 to 1987). METHODS: Patients were divided into three groups according to the number of units transfused during the perioperative period: group 1, 0 units (n = 440), group 2, 1 to 2 units (n = 746), and group 3, 3 or more units (n = 599). RESULTS: With univariate analysis, no statistically significant differences were found among the three groups in overall survival rate (71%, 75%, and 71% at ten years; p = 0.48), cause-specific survival rate (89%, 88%, and 86% at ten years; p = 0.36), or progression-free survival rate (61%, 68%, and 68% at ten years; p = 0.83). Adjusting for tumor grade, pathologic stage, and hormonal therapy using the Cox statistical model, we found no significant association between the blood-use group and overall survival rate (p = 0.45), cause-specific survival rate (p = 0.17), or progression-free survival rate (p = 0.34). The estimated relative risk and 95 percent confidence interval associated with blood transfusion (three or more units versus none) were as follows: 1.03 and 0.76 to 1.38 for total mortality, 1.56 and 0.95 to 2.56 for cause-specific death, and 1.20 and 0.91 to 1.57 for disease progression, respectively. CONCLUSIONS: According to these findings, withholding homologous blood transfusion, except for infectious precautions, should not be based on the suspicion that it can accelerate death from cancer in patients who undergo radical prostatectomy for prostate cancer. PMID- 8197647 TI - The time for serum testosterone to reach castrate level after bilateral orchiectomy or oral estrogen in the management of metastatic prostatic cancer. AB - OBJECTIVE: To understand the time for serum testosterone to reach castrate level after bilateral orchiectomy or oral estrogen in the management of metastatic prostatic cancer. METHODS: A total of 20 consecutive patients with adenocarcinoma of the prostate with bony metastasis were enrolled in this study. Their mean age was 72.8 years old (range, 57 to 82 years). Pretreatment serum testosterone levels were obtained in all men. Thirteen men were treated with bilateral orchiectomy. Immediately after removal of testes, serial blood samplings for serum testosterone levels were drawn every fifteen minutes for the first two hours, then hourly for another sixteen hours. Seven men were treated with oral estrogen diethylstilbestrol (DES), 3 mg per day. Serum testosterone levels were checked on a weekly basis for two months, and then biweekly for another two months. RESULTS: Castration time of bilateral orchiectomy ranges from three to twelve hours (mean, 8.6 hours). The biological half-life of serum testosterone was from thirty to sixty minutes (mean, 45 minutes). Castration time of oral estrogen (DES) was from twenty-one to sixty days (mean, 38.3 days). CONCLUSIONS: Bilateral orchiectomy and oral estrogen were both effective ways of castration for patients with bony metastatic prostatic cancer. Bilateral orchiectomy provides a more rapid castration and is one hundred seven times faster than oral estrogen in reaching castrate level. PMID- 8197648 TI - Improved hemodynamic response after long-term intracavernous injection for impotence. AB - OBJECTIVE: To investigate the phenomenon of spontaneous erections in patients on long-term intracavernous injection therapy. METHODS: We undertook an objective assessment of the penile circulation of 35 patients; 21 used prostaglandin E1 (PGE1) alone and 14 used a combination of papaverine, phentolamine, and PGE1. All underwent duplex ultrasonography before initiation of home self-injection and again after a mean of thirty-one months of treatment (most patients performed injections once or twice a week). RESULTS: The diameter of the cavernosal arteries did not change significantly after treatment. However, the mean peak flow velocity increased highly significantly (P < 0.001): 17.9 cm/second in the right cavernous artery and 21.2 cm/second on the left before treatment; 24 cm/second on the right and 29 cm/second on the left after treatment. More than one third (13 of 35 patients [35%]) achieved functional erection without injection at least some of the time, giving clinical support to the sonographic findings. CONCLUSIONS: We suggest that the combination of vasodilatory drugs and sexual stimulation may act to improve sinusoidal and penile arteriolar smooth muscle function. PMID- 8197649 TI - Ureterocele associated with a single collecting system of the involved kidney. AB - OBJECTIVE: This is a study concerning ureteroceles associated with a single collecting system of the involved kidney. METHODS: Over an eight-year period 9 children (5 boys, 4 girls) had a ureterocele subtending a single collecting system, whereas 63 children had duplex ureteroceles. Malformations of other organ systems were present in only 1 patient. RESULTS: Three patients have undergone surgical interventions: a transurethral incision of bilateral obstructive ureteroceles in 1 and nephroureterectomy in 2. In 4 cases cystic/dysplastic kidneys involuted and were reabsorbed with collapse of the ureteroceles. The last 2 patients have received antibiotic treatment for single episodes of a urinary tract infection. CONCLUSIONS: Earlier reports of a high incidence of concomitant anomalies and male predominance in patients with single-system ectopic ureteroceles could not be verified by our experience. Our current policy for a patient is careful evaluation, individualized therapy, and long-term surveillance. PMID- 8197651 TI - Urologic laparoscopy with a new blunt-tipped trocar: safe, rapid access without the use of fascial sutures. AB - Fifteen patients underwent successful laparoscopic procedures where a new blunt tipped trocar was used both to gain initial access to and to insufflate the abdominal cavity. The use of this new trocar obviates the need for the use of the Veress needle and appears to be both time-saving and possibly safer. Unlike the Hasson-type trocar, the blunt trocar technique does not require the use of fascial sutures for prevention of air leaks. PMID- 8197650 TI - Long-term effects of polytetrafluoroethylene injected into the rat bladder submucosa. AB - OBJECTIVE: The use of polytetrafluoroethylene (PTFE) paste in the lower urinary tract for the treatment of vesicoureteral reflux or urinary incontinence is increasing. Its use remains controversial and the long-term consequence of this substance injected into the lower urinary system of humans is largely unknown. When injected into the bladder submucosa, PTFE paste has been shown to elicit a foreign body reaction with chronic inflammation and possibly granuloma formation. Whether these inflammatory changes result in neoplastic changes over the long term has yet to be determined. The purpose of this study was to evaluate histologically the potential for submucosal PTFE paste to induce bladder neoplasia in a rodent model, realizing that others have shown an increased tendency for such alloplastic materials to produce sarcomas in these animals. METHODS: Sixteen experimental animals and 4 control animals were sacrificed at various time intervals and evaluated for systemic and local tumor formation following submucosal injection of PTFE paste in the bladder. A time well beyond the equivalent of the latency period believed to be necessary for the induction of tumors in humans (15 months) was evaluated. RESULTS: On sacrifice, histologic changes consistent with encapsulation and chronic inflammation were evident, but there was no evidence of either epithelial or sarcomatous tumor formation. CONCLUSIONS: A quiescent foreign body reaction occurs when injecting PTFE into the bladder submucosa of rodents. Urologic use of PTFE has never been proven to induce tumors in humans or animals. PMID- 8197652 TI - Minimally invasive endourologic management of calculi in continent urinary reservoirs. AB - This study was done to determine whether minimally invasive endourologic management of calculi in continent reservoirs can be done effectively without compromise of urinary continence. Four patients with continent urinary diversions (1 Indiana pouch and 3 Kock pouches) were managed with trans-stomal pouchoscopic ultrasonic lithotripsy (n = 2), prone position extracorporeal shock wave lithotripsy (n = 1), or a "sandwich" combination of these (n = 1) for stone burdens up to 20 cm2. Total hospital stay ranged from one to four (mean = 2.6) days. All 4 patients were initially rendered stone free, and, with follow-up as long as twenty-five months, only 1 has had a recurrence. No patient experienced stomal leakage or other complications. This study suggests that minimally invasive endourologic management of calculi in continent urinary reservoirs can be done safely and effectively to obviate the need for more invasive percutaneous approaches or open surgery, even for some patients with large stone burdens. PMID- 8197653 TI - Use of magnetic resonance imaging scanning in adrenocortical carcinoma with vena caval involvement. AB - We report on 2 cases of an adrenocortical carcinoma with vena caval involvement. Preoperative evaluation included a magnetic resonance imaging (MRI) scan confirming the presence of vena caval involvement. Extremely precise detail of the vena caval tumor thrombus was very helpful in preparing for the surgical extirpation. MRI detail far outweighed what was seen on the computed tomography scan and venacavogram. The MRI scan correlated exactly with what was found surgically. Although MRI scanning has been used to evaluate renal tumors with vena caval extension, few cases have been reported with similar adrenal tumors. PMID- 8197654 TI - Laparoscopic bilateral nephrectomy for renin-mediated hypertension. AB - Hypertension arising from retained native kidneys complicates the management of recipients of renal transplants. Reluctance to administer angiotensin-converting enzyme inhibitor (ACEI) drugs to patients taking cyclosporine has reopened the question of performing native nephrectomies for poorly controlled, renin dependent hypertension. We report the first published cases of simultaneous bilateral laparoscopic nephrectomies in 2 patients: 1 in preparation for living related donor transplantation and the other ten months following cadaver transplantation in a patient whose end-stage renal disease was from malignant nephrosclerosis. Both had very severe hypertension resistant to multiple drugs and both became normotensive with little or no antihypertensive medication following nephrectomies. A bilateral nephrectomy is currently feasible using a laparoscopic approach. PMID- 8197655 TI - Extracorporeal urinary bypass for malignant ureteral obstruction. AB - Extracorporeal urinary bypass was attempted in a patient with malignant ureteral obstruction. A nephrostomy was drained into the bladder by connecting the tube to a cystostomy catheter. This method made the patient free from a collecting bag without any significant complications. This method may improve the quality of life of patients with malignant ureteral obstruction, when their bladder is intact. PMID- 8197656 TI - Paravesical cystic retroperitoneal lymphangioma presenting as recurrent vesicoureteral reflux. PMID- 8197657 TI - Koro: the delusion of penile retraction. AB - Koro is a psychiatric syndrome in which the patient is convinced his penis is retracting. A case of koro is described. The literature and proper approach to such patients are briefly summarized. PMID- 8197658 TI - Fixed drug eruption to papaverine. AB - Papaverine has offered new options for therapy in erectile dysfunction. Various complications have been reported with papaverine, the prominent ones being priapism and liver function abnormalities. We present a previously unreported case of a fixed drug eruption caused by papaverine. PMID- 8197659 TI - Autoaugmentation omentocystoplasty in a sheep model. AB - OBJECTIVE: To develop a sheep model of autoaugmentation omentocystoplasty and study the histologic appearance, and to compare the urodynamic results with a control group. METHODS: Ten male lambs underwent a bladder autoaugmentation reinforced with an omental patch. Three were culled early, to study urothelial survival and inflammatory changes. One was sacrificed at six months to assess late histologic changes; five sheep had a urodynamic study at that stage and two died of unknown causes without further investigation. A group of seven six-month old male sheep, of similar weights, formed the control urodynamic group. RESULTS: The urothelial lining remained viable under the omentum, but marked inflammation and heterotopic calcification were seen within the subepithelial tissues in most of the animals. The histologic changes were reflected in the bladder dynamic data, which were no better than the control group; the average compliance value was 9.2 +/- 6.4 mL/cm H2O, compared to the control group figure of 11.8 +/- 5.2 mL/cm H2O. CONCLUSIONS: It would appear that autoaugmentation alone does not usually produce bladder augmentation in the sheep. PMID- 8197660 TI - [Individuality and collectivism]. PMID- 8197661 TI - [Stringent responsibilities of the physician in pregnancy termination. The decision of the 28 May 1993 federal court mandates new guidelines]. AB - In declaring abortion during the first 12 weeks of pregnancy fundamentally illegal but not punishable, the Federal Constitutional Court wants to guarantee the constitutionally necessary protection of the embryo by intensifying counselling and help for the pregnant woman. The physician to whom the woman has turned to have an abortion is thus included in the procedure. He is, however, obliged by professional ethics and law to use all his influence basically for the preservation of human life--including unborn human life. His obligation to counsel and inform is thus extended. In his counselling he is to include the woman's conflicting views about abortion beyond the pure medical aspect. He is to ascertain the reasons why the woman demands abortion. He is to try to find out about the deeper reasons (e.g. the influence of the family and of the social environment) and is thus to point out the dangers of subsequent psychological disorders. PMID- 8197662 TI - [Medical responsibility. An overview of recent legislation (status: February 1994)]. AB - 1. It's only about the legal liability of the doctor for compensation in case of non properly treatment of a patient. It's not about a causal liability, but about a model liability, and it is sufficient not having observed the required standards. Having assessed the liability grounds (not keeping of the required standards) the patient must prove that this treatment had led to damages. If it is a significant medical mistake the doctor must prove, that there was no effect in order to escape a liability. 2. The standards often not will be carried out because the doctor in attendance (beginner) assume a treatment, which he is not up to or the technical equipment is not sufficient. Even if the hygiene is not sufficient the burden of proof can be changed in emphasis to the doctor. 3. Some medical examples will shortly clarify the problems of liability. PMID- 8197663 TI - [Suicide from the diagnostic and legal viewpoint]. PMID- 8197664 TI - [Quality criteria in psychiatric expert practice]. AB - Aspects of quality control are of significant importance in the field of psychiatric expertise. Better transparency and reliability should be aimed at. Formal quality criteria refer to organization, duration and extent of psychiatric exploration. Diagnosis should be made according to DSM-III-R or ICD-10 criteria. Estimation of individual degree of disability is necessary. Patients with neurotic or personality disorder require particular experience and qualification. Psychodynamic aspects of expert-patient-interaction should receive special attention. Limits of psychiatric expertise must be outlined. PMID- 8197665 TI - [Neurologic-psychiatric expert assessment in 1989 to 1991 social law]. AB - With 100 Social Court proceedings instituted in Germany (according to the territory of 1989), there could be shown the law-suits not being based on substantial arguments in two thirds and, therefore not having chances of success in foro. Among medical expert testimonies concerning with psychiatric matters female plaintiffs predominated; in contrast, neurologic testimonies were predominantly requested for males. The proportion of foreigners amounted to 5-15% depending from the matter on which testimony was requested. Mean age of the plaintiffs was approximately 50 years, they had been retired from business life on an average of 3 years before. Two thirds of the plaintiffs briefed an attorney or a representation of interests for instituting legal proceedings; the latter did not result in charges to the plaintiffs. Medical examinations to elaborate the testimony included tests employing technical measures such as neuroimaging in about one third of the cases. Relating to the latter, there is an increasing tendency obviously. PMID- 8197666 TI - [Prognosis after stroke]. AB - The outcome of 100 own cases of acute ischaemic cerebral infarction was investigated and the literature was reviewed in order to identify factors of prognostic relevance in ischaemic cerebral infarction and spontaneous intracerebral haematoma. Intentionally not taking into account the various pharmacological treatment strategies, the following factors were investigated: the initial acute clinical symptomatology including psychopathological features, the severity and extent of the underlying structural lesion, the time span between onset of symptoms and start of treatment, facilities for early and later rehabilitation measures, existing risk factors, the age of the patient and his or her social relations. These parameters were evaluated in relation to a realistic therapeutic goal defined for each individual case. Results indicate that the following items seem to be connected with a more favourable prognosis: A more circumscript disease process without relevant psychopathological defects, especially without dementia, an intact family background or corresponding favourable social environment, the absence or successful management of risk factors, an early onset of therapy and facilities for early and subsequent rehabilitation measures. PMID- 8197667 TI - [Longevity of patients with Alzheimer's disease]. AB - Probability of survival was investigated in a sample of 90 patients with Alzheimer's disease of mild to moderate severity over a period of 36 months. It showed a decline of approximately 10 per cent per year of observation. This is equivalent to an excess mortality of 21 as compared with the age-matched population. The estimated survival rate was analysed with regard to the influence of sex, and of age and severity of cognitive impairment at the initial examination. The most powerful predictor for a reduced probability of survival was the degree of cognitive impairment at study entry. PMID- 8197668 TI - [Querulous patients]. AB - Querulousnes is no uniform psychiatric phenomenon and no disease entity. Causes and occasions are of the most various types, difficult to compare between persons, often moulded by the currents of the day, inherited ways of thinking, experiences and environment. Querulants are personalities, who, after colliding with the legal system and having had their own claims dismissed, suffer from an often chief and irremediable feeling of being victim of an injustice. They cannot understand that, what is in due form valid can, when, scrutinized with the greatest sense of justice and practical common sense, impress upon someone as injustice. The submission to the unattainable, the parting from hopes, expectations and claims do not materialize. The step by step stiffening readiness for action can be confined to the lawsuit matter, it comes however about, that it extends to further spheres of life. Escalations occur in particular then, when the authorities course of action, courts of justice and opponents are felt as tyrants or mortal threat. A person deriving a meaning from his entire life or events, which he interprets for himself, makes his relations to the community and Law fragile [90]. Are presented within the framework of differential diagnostic distinctions, manifestations of querulous behaviour among abnormal personalities, neurotic disorders and schizophrenic psychoses under psychiatric aspects. Brought into sharper focus are the psychogenic psychoses, which became manifest in the USA, GUS and scandinavian countries in connection with serious querulous evolutions. Hints to decision of the supreme court and forensic psychiatric expert opinion conclude the article. PMID- 8197669 TI - Historical and veterinary perspectives of surgical stapling. PMID- 8197670 TI - Stapling instrumentation. AB - A number of surgical stapling instruments are on the market. The variety of instruments, stapling cartridges, and their potential veterinary uses are discussed. The basic principles of application and operation of these devices are emphasized. PMID- 8197671 TI - Gastric surgery with surgical stapling instruments. AB - The use of stapling instruments to perform gastric surgery in small animal patients provides alternative techniques that are often more reliable and are usually performed more quickly than conventional techniques with manual sutures. In addition to reducing anesthetic and operating times, the risk of contamination of the abdominal cavity may be decreased significantly. PMID- 8197672 TI - Surgical stapling of the small intestine. AB - Intestinal resection and anastomosis, bypass enterostomy, and typhlectomy are indicated for many intestinal disorders. The thoracoabdominal and end-to-end anastomosis stapling instruments all may be used to perform a variety of small intestinal surgical procedures. PMID- 8197673 TI - Surgical stapling of large intestines. AB - Surgical stapling instruments can be used to perform end-to-end anastomoses in the colon and rectum. A new method of colonic anastomosis is described for cats with acquired forms of megacolon. Alternative approaches for performing colonic anastomoses are described in humans and in large dogs which can be used for colonic resections of focal nature as well as for subtotal colectomy. Advantages and disadvantages of surgical stapling instruments in the large intestine are reviewed. PMID- 8197674 TI - Stapling techniques in pulmonary surgery. AB - There are only a few reports in the veterinary literature describing the use of stapling equipment and techniques for pulmonary surgery. These reports indicate that complications associated with these procedures are minimal. Although pulmonary lobectomy procedures originally described independent isolation and ligation of the hilar vessels, it became apparent that, with the use of the smaller staples, especially the ones designed for vascular use, this was unnecessary. Therefore, en bloc hilar stapling is the procedure of choice. This makes the surgical procedure extremely quick to perform. Similarly, there is no indication to routinely oversew staple lines when performing a partial lobectomy. This is a tedious procedure and may actually increase the chance of air leakage. If point areas of leakage do occur, these can be independently occluded either with sutures or individual vascular clips. Selecting the correct size of TA stapler and staples to create the correct length of staple line is critical. It is important that all the tissue to be ligated lie comfortably within the staple line. It is better to use a stapler that is too long and collect the extra staples on a sponge than to use one that is too short that results in leakage from nonstapled tissue. In general, the 4.8-mm staples should not be used for pulmonary surgery in the dog and cat. They do not compress the tissue enough to prevent leakage. For most complete lobectomies, where the hilus of the lung can be adequately isolated, the TA 30 V3 is the stapler of choice. When performing a partial lobectomy, a longer stapler is often required. If a TA 55 or TA 90 is necessary, it should be used with 3.5-mm staples. Even though stapling techniques have made pulmonary surgical procedures safe, easy, and quick to perform, they are not totally free of problems and complications. Experience in the use of the equipment is essential, as is good surgical judgment as to when to use or not to use these techniques. The absence of reported clinical complications, either short- or long-term, attests to the success of these techniques. PMID- 8197675 TI - Surgical stapling devices in cardiovascular surgery. AB - Stapling devices useful for cardiovascular applications include vascular clips, the ligation and division stapler, the thoracoabdominal stapling device with vascular load, and the pin-ring device of small vessel anastomosis. This article addresses the application, indication, advantages, and disadvantages of each of these devices. PMID- 8197676 TI - Surgical stapling of the spleen, pancreas, liver, and urogenital tract. AB - Stapling instrumentation designed primarily for specific gastrointestinal procedures and transection of vascular pedicles have been adapted for use in parenchymal organs of the abdomen and urogenital tract. This article reviews current veterinary clinical and experimental use of stapling instrumentation for splenic, pancreatic, hepatic, and urogenital surgery. PMID- 8197677 TI - Stapling in esophageal surgery. AB - Indications for esophageal surgery include the closure of tears from foreign bodies and incisions for their removal, esophageal anastomosis after removal of diseased or nonfunctional segments, esophagogastric anastomosis after major gastric resection, removal of esophageal diverticula, resection of fistulas, and esophageal reconstructive surgical techniques. The potential use and application of surgical stapling instruments for these esophageal disorders in the veterinary patient are discussed. PMID- 8197678 TI - Skin and fascia staple closure. AB - Skin stapling is the fastest method of closure for long skin incisions. In addition, clean-contaminated wounds closed by staples have a greater resistance to infections than wounds closed with suture. It is important to realize that staples are a particular modality of suturing live tissues and if used properly they add speed and precision to wound closure. Many skin staplers are available to the veterinary surgeon and most perform satisfactorily. Stapling may be economically feasible when the reduced cost of surgical time and anesthesia is considered. PMID- 8197679 TI - Natural transmission of foot-and-mouth disease virus from African buffalo (Syncerus caffer) to cattle in a wildlife area of Zimbabwe. AB - An outbreak of foot-and-mouth disease (FMD) occurred during April 1991 in a trypanosomiasis sentinel cattle herd by the Rifa River to the east of Lake Kariba, Zimbabwe. Despite the cattle having been vaccinated biannually for the previous five years the disease was severe. The viruses isolated from the affected animals were typed as FMD virus type SAT 1. Free-living African buffalo (Syncerus caffer) which had been using the same watering place as the affected cattle were sampled and FMD type SAT 1 virus was isolated. Partial nucleotide sequencing of the gene coding for the capsid protein 1D (VP1) of one of the viruses isolated from cattle and two of the viruses isolated from buffalo demonstrated a close relationship between the three viruses. Since no other cattle were present in the area and no outbreaks of SAT 1 had occurred in Zimbabwe since 1989, it was concluded that the disease had been transmitted from buffalo to cattle. PMID- 8197680 TI - Spinal muscular atrophy in calves of the Red Danish dairy breed. AB - Pathological and genetic aspects of spinal muscular atrophy in Red Danish dairy cattle are described. A total of 312 calves suspected of having the condition was reported in the Danish Bovine Genetic Disease Programme, 162 of them were examined post mortem and spinal muscular atrophy was diagnosed in 82 of these. Seventy-five per cent of the affected calves had bronchopneumonia. The diagnosis of spinal muscular atrophy was based on histopathological examinations of the spinal cord and musculature. The lesions were primarily characterised by degeneration of the spinal cord motor neurons with neuronophagia and denervation muscular atrophy. The ages of the affected calves varied from those recumbent from birth to a 21-week-old calf. All the necropsied cases appeared in a clearly familial pattern and could be traced back to American Brown Swiss bulls. PMID- 8197681 TI - Effect of subclinical Eimeria species infections in tropical goats subsequently challenged with caprine Haemonchus contortus. AB - Fourteen goat kids of the local indigenous breed naturally infected with Eimeria species were divided into two equal groups. The first group was superinfected with 500,000 Eimeria species oocysts and the second group was treated with amprolium. Sixty days later both groups were infected with 5000 third-stage caprine Haemonchus contortus larvae. The goats experimentally superinfected with eimeria shed more H contortus eggs and gained weight more slowly. PMID- 8197682 TI - A preliminary study of peripheral lymphocyte function in cows with chronic endometritis. PMID- 8197683 TI - Nasopharyngeal mast cell tumour in a horse. PMID- 8197684 TI - Use of the polymerase chain reaction to detect mycoplasma DNA in cattle with contagious bovine pleuropneumonia. PMID- 8197685 TI - Trisomy-X in a sterile river buffalo. PMID- 8197686 TI - Effect of a vitamin E-selenium combination on chickens infected with infectious bursal disease virus. PMID- 8197687 TI - Draft report of the joint RCVS/BVA review group on continuing professional development. PMID- 8197688 TI - BST ban. PMID- 8197689 TI - Prevalence of FeLV in sick cats. PMID- 8197690 TI - Carbofuran poisoning in cats. PMID- 8197691 TI - Deaths from bee stings. PMID- 8197692 TI - Re-examination of Pasteurella multocida serotypes that caused haemorrhagic septicaemia in North America. PMID- 8197693 TI - The bovine placentome in bacterial and mycotic abortions. AB - Placentomes were extracted from the uteri of 22 aborted cows and examined to detect the cause of abortion; fetuses or fetal abomasal contents from 15 of the cows were also examined. Firm diagnoses of Pasteurella haemolytica, Actinomyces pyogenes, Listeria monocytogenes, Bacillus licheniformis, Aspergillus fumigatus or Mortierella wolfii abortion were made in 11 cases. The histopathological lesions showed some correlation with the identity of the bacterium isolated; the lesions of mycotic abortion were distinct and characterised by a coagulative necrosis. The removal of a placentome was not followed by any observable deleterious effects. PMID- 8197694 TI - Effect of buserelin on pregnancy rates in dairy cows. AB - Three field trials were carried out to assess the effect of buserelin on the fertility of dairy cows. In the first, 10 micrograms of buserelin was injected on the day of insemination; there were no significant effects on fertility in comparison with untreated control cows. In the second study the cows were injected 12 days after insemination; the mean pregnancy rates to first insemination were 53.4 and 65.4 per cent for the control and treated cows, respectively (P < 0.01) and the mean pregnancy rates to repeat inseminations were 52.9 and 59.4 per cent for the control and treated cows. The mean calving to conception intervals were 91.4 and 85.3 days (P < 0.01) and the incidences of barren cows were 10.2 and 5.2 per cent. In the third study the cows were injected with buserelin either eight days or 10 days after insemination; there were no significant effects on fertility in comparison with untreated control cows. PMID- 8197695 TI - A disease monitoring system for dairy herds. AB - A system for recording and evaluating disease, intended for both dairy herd health monitoring and research purposes, is described. The system was initiated in 1960 with the objective of providing a research database and it has been developed to respond to the herd health management needs of modern farmers and veterinarians. The system is probably one of the oldest disease recording systems in existence and has contributed to the expansion of epidemiological knowledge of dairy cattle diseases and has helped to improve the health management of dairy herds. The history of the system, the herd reporting form and various analyses and reports generated with the system are presented. PMID- 8197696 TI - Decline in the incidence of BSE in cattle born after the introduction of the 'feed ban'. PMID- 8197697 TI - Direct rehydration of in vitro fertilised bovine embryos after vitrification. PMID- 8197698 TI - Fat absorption in female boxer dogs with undiagnosed hormonal alopecia. PMID- 8197699 TI - CPD review. PMID- 8197700 TI - Foot-and-mouth disease and treatment of cattle feed with caustic soda. PMID- 8197701 TI - Leptospira hardjo infection in sheep. PMID- 8197702 TI - Bluetongue disease in dogs associated with contaminated vaccine. PMID- 8197703 TI - Suspected giardiasis in a Welsh pony. PMID- 8197704 TI - Theobromine poisoning in dogs. PMID- 8197705 TI - Effects of acetamide on experimentally-induced Palicourea marcgravii (St Hill) poisoning in rats. AB - High indices of mortality in cattle have been reported in Brazil as a consequence of Palicourea marcgravii (Pm) acute intoxications. It has been established that Pm leaves contain monofluoroacetic acid (MFA), the active toxic principle of the plant. Rational therapy for MFA poisoning involves the use of a substance that might prevent fluorocitric acid formation. The present work was undertaken to verify if acetamide, a MFA antidote and an acetate donor, protects rats against both Pm and MFA intoxications. It was verified that acetamide protected rats from both convulsions and death. Future experiments should be carried out on cattle to examine the efficiency of acetamide, and particularly under field conditions. PMID- 8197706 TI - Clinical manifestations and leukocyte neurotoxic esterase and red blood cell and plasma acetylcholinesterase activities in swine following a single oral dose of tri-o-cresyl phosphate. AB - We report the clinical signs and the effects on leukocyte neurotoxic esterase and red blood cell and plasma acetylcholinesterase (AChE) activities in swine orally administered a single dose of tri-o-cresyl phosphate (TOCP) at 400, 800 or 1000 mg/kg. Swine in all dosage groups exhibited signs consistent with inhibition of nervous tissue cholinesterase 3-48 h after TOCP administration. Onset was dose related, and 2/3 1000 mg/kg dosed swine died 3 or 35 h postdosing. In surviving swine, significant depressions in plasma AChE activity were apparent at 6 h postdosing, ranging from 16-23% of predosing levels. Similar depressions of red blood cell AChE were not observed until 24 h postdosing. Plasma AChE activities appeared to more accurately reflect the development of acute cholinergic signs observed in the 1000 mg/kg dosed swine at 3 h postdosing while red blood cell AChE activities were more consistent with the delayed cholinergic signs exhibited by the 400 and 800 mg/kg dosed swine at 24 h postdosing. All survivors developed signs of delayed neurotoxicity 10-12 d after TOCP administration, and 70% or greater inhibition of neurotoxic esterase activity in leukocytes was apparent during the first 48 h postdosing. PMID- 8197707 TI - Hematologic response of adult brown mink to oxidative stress. AB - We evaluated the response of mink to oral administration of the oxidant compound propylene glycol (PG) to better understand the relative susceptibility of mink red blood cells (RBC) to oxidant injury. Feeding a diet containing 12% PG to 6 mink for 1 w resulted in a 17% decrease in hematocrit, a 21% decrease in RBC count and a 4.8-fold increase in reticulocyte count. A marked increase in Heinz body and eccentrocyte numbers was consistent with oxidative injury to RBC. Because of high food intake, mink ingested approximately twice the quantity of PG/kg body weight compared to domestic cats fed diets containing 12% PG. Therefore, the severity of the hematologic dyscrasia in mink may be the result of greater intake of PG rather than unique sensitivity of mink RBC of oxidative injury. However, the high food intake and the mink's position at the top of the food chain may increase its exposure to environmental contaminants. PMID- 8197708 TI - The risk associated with poisonings in children. AB - The risk associated with poisonings in children was assessed on 6175 subjects admitted to the pediatric hospitals of 3 regions of Northern Italy between 1975 and 1990. The frequency of exposures and the severity of sequelae allowed high- and low-risk substances to be identified. Risks were studied separately in the 0 4, 5-9 and 10-13 y age group to determine age-related differences. A decrease in drug-related poisonings and an increase of those caused by household products, particularly in the first 2 y of life, were observed in 1983-90 as against 1975 82 in association with the introduction of safety caps and containers for drugs. Our study points out the need to strengthen active primary prevention through health education and parental and adolescent information, and to improve passive prevention through the extension of safety closures to household products. PMID- 8197709 TI - Effects of honey containing grayanotoxin I on frog gastrocnemius muscle. AB - The presence of grayanotoxins (GTX-I, GTX-II and GTX-III) in honey samples from the Mediterranean Sea and Black Sea regions of Turkey and the effect of honey containing GTX-I on the threshold stimulus voltage of frog gastrocnemius muscle were studied. We used 2 groups of gastrocnemius muscles isolated from curarized or noncurarized frogs. The threshold voltage was measured by external perfusion with a polygraphic system. Isolated muscle preparations were perfused separately with Clark-frog-Ringer's solution containing honey solutions from the Mediterranean Sea region (normal) or with honey solutions from the Black Sea region (GTX-I-containing, poisonous). There was no significant difference between the normal and poisonous honey groups data with the curarized preparations. But in the noncurarized preparations, the honey containing GTX-I significantly decreased the threshold voltage in comparison with normal honey. These findings suggest the effect of GTX-I on frog neuromuscular junctions is due to an increase in membrane permeability to sodium ions. PMID- 8197711 TI - The teratogenic potential of bone wax extract in rats. AB - This study evaluated the teratogenic defects of rat brain, eye, heart, urogenital and skeletal systems after po administration of bone wax saline extract on days 9 13 of gestation. The experiment involved 5 groups of 6 pregnant wistar rats each. The vehicle control group received only 50.0 ml distilled water/kg; 3 test groups received 12.5, 25.0 or 50.0 ml of bone wax saline extract/kg; and the last group received 100 mg caffeine/kg as positive control. On the 21st day of gestation all the animals were sacrificed under ether anesthesia and fetuses were collected for routine teratological evaluations. There was no significant change in maternal body weight or food consumption and no external, visceral, skeletal and histological abnormalities in the vehicle control and bone wax dosed groups. Abnormalities were observed in the positive control group. PMID- 8197710 TI - Effects of a pyrethroid type II pesticide on conditioned behaviors of rats. AB - Our present work investigated the effect of fenvalerate, a pyrethroid type II pesticide, on conditioned behaviors of rats. Pre-training administration of the pesticide did not modify passive avoidance but decreased active avoidance responses and operant conditioned responses; pre-training or pre-test administration of fenvalerate induced a facilitatory effect on passive avoidance task; pre-training and/or pre-test treatments reduced active avoidance responses of rats which received the pesticide before test; and post-training treatments were not capable of modifying both active and passive avoidance responses. Increased emotionality produced by the action of fenvalerate on the sympatho adrenal system could be responsible for the differences observed between active and passive avoidance responses. PMID- 8197712 TI - Dermal toxicity of nickel and chromium in guinea pigs. AB - Liver and kidney enzyme activities and blood glucose and hemoglobin increased after 15 or 30 d of dermal exposure to nickel and chromium. Concentration of nickel and chromium increased in tissues. The changes were related to the duration of exposure. PMID- 8197713 TI - Herb-induced aconitine poisoning presenting as tetraplegia. AB - Both "chuanwu", the main root of Aconitum carmichaelii, and "caowu", the dried root of Aconitum kusnezoffii or other members of the Aconitum genus, have long been used in Oriental materia medica to treat rheumatism, arthritis, bruises, fractures and cardiac complaints. These herbs contain the highly toxic diterpene alkaloids aconitine, mesaconitine and hypaconitine. A case of aconitine poisoning due to chuanwu and caowu that is described presented as profound tetraplegia. PMID- 8197714 TI - The spectrum of poisonings in Hong Kong: an overview. AB - Poisoning is an important health problem in Hong Kong. In 1990 alone, 6500 patients were treated in Hong Kong hospitals and there were 245 deaths. Two hospital-based studies indicated that exposures to poisons were intentional in the majority (96%) of adult cases, with hypnotics/sedatives (34%), household products (16%) and analgesics (14%) being most often used. Apart from drugs and chemicals, accidental poisoning may occur after the ingestion of Chinese medicines or vegetables contaminated with methamidophos. The former may contain highly toxic aconitine or podophyllin, declared and undeclared western drugs such as phenylbutazone and aminopyrine, and heavy metals. It is important that there be a continuing effort to collect information on the factors leading to and the pattern of poisonings in Hong Kong and other Southeast Asian countries. This is particularly valuable for childhood poisoning so that appropriate preventive measures can be taken. PMID- 8197715 TI - Use of permethrin as a miticide in the African hedgehog (Atelerix albiventris). AB - The African hedgehog, Atelerix albiventris (also known as Erinaceous albiventris; 1,2) has recently undergone an increase in popularity as an exotic pet. This popularity (Beatrix Potter not withstanding) is due in part to the small size of the African hedgehog (adults are 4-6 in in length, weighing approximately 1 lb), its lack of hibernation or aestivation if reared under controlled light and temperature, and its general good nature and accommodation to handling. PMID- 8197716 TI - Toxicity of melaleuca oil and related essential oils applied topically on dogs and cats. AB - Cases of melaleuca oil toxicosis have been reported by veterinarians to the National Animal Poison Control Center when the oil was applied dermally to dogs and cats. In most cases, the oil was used to treat dermatologic conditions at inappropriate high doses. The typical signs observed were depression, weakness, incoordination and muscle tremors. The active ingredients of commercial melaleuca oil are predominantly cyclic terpenes. Treatment of clinical signs and supportive care has been sufficient to achieve recovery without sequelae within 2-3 d. PMID- 8197717 TI - The status and future of toxicology in Europe. AB - This overview shows that toxicology in Europe is progressing well both quantitatively and qualitatively. However, a better recognition of key toxic issues is needed, particularly among health specialists. In this, teaching should play a pivotal role. PMID- 8197718 TI - The status and future of toxicology in Japan and the Pacific rim. PMID- 8197719 TI - Children's chewable multivitamin plus iron ingestions. PMID- 8197720 TI - Identifying unknown tablets and capsules: use of a new tool. PMID- 8197721 TI - Food safety and radiation. PMID- 8197722 TI - The influence of Datura ferox alkaloids on egg-laying hens. AB - Seeds of the weed Datura ferox are frequent contaminants of raw materials used for animal feed. In this study a mixture of scopolamine and hyoscyamine (98:2), the 2 main alkaloids of Datura ferox seeds, was incorporated at 4 total alkaloid levels (1.5, 15, 75 or 150 mg/kg feed) into a control diet fed to 100 egg-laying hens for 3 mo. Alkaloid doses of 150 mg/kg feed reduced egg production for the first 5-6 w of feeding, whereas lower doses had no effect. Egg weight, eggshell thickness and body weight of hens were unaffected at all doses. Doses of 150 mg/kg feed produced significant increases in the cardiac rate of hens after 5 w. Breathing frequency at all doses was unaffected. Determination of plasma aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and leucine aminopeptidase activities, as well as autopsy and histological examinations, revealed no obvious alkaloid-related toxic effects. It was concluded that a total alkaloid dose as high as 75 mg/kg feed can be safely administered to egg-laying hens. PMID- 8197723 TI - Toxigenic strains of Stachybotrys atra associated with poisonous straw in Morocco. AB - From 10 moldy straw samples collected in a Moroccan area with an apparent equine stachybotryotoxicosis outbreak in November 1991, 8 isolates of Stachybotrys atra were obtained. They all showed toxigenesis, however they were variable in nature and intensity. While 1 isolate had only mild toxicity when fed to mice as moldy barley, another revealed very high toxicity to Artemia saline larvae, or rat skin, and to mice. The toxicity of the other 6 isolates were between these 2 limits. This study indicates that the November 1991 outbreak was due to toxigenic strains of Stachybotrys atra. PMID- 8197724 TI - Antinutritional effects of Crotalaria ochroleuca (marejea) in animal feed supplements. AB - Antinutritional effects of Crotalaria ochroleuca (marejea) in animal feed supplements were studied in rats fed marejea supplemented rations. Six rations supplemented with 10, 30 or 50% marejea seed or leaf meals were tested for toxic effects compared with 1 control ration. Thirty-five mature rats whose mean weight was 55.8 g were randomly assigned to the 7 rations. The daily performance was observed. After 35 d of the feeding, the rats were killed and a postmortem examination was performed to assess the condition of the internal organs. Mean daily gains were 0.15 and 0.93 g, total gains were 5.20 and 32.55 g, and the final weights were 163.42 and 188.75 g for the rats on marejea seed and marejea leaf meals, respectively. Growth performance deteriorated with increasing levels of seed and leaf supplementation. Rats on 10% marejea leaf meal had normal growth performance. Postmortem examination showed that internal organs of animals on 30 or 50% marejea seed and 50% marejea leaf meals were severely damaged. Rats on 10% marejea leaf meal had normal internal organs. It appears that supplementation with marejea leaf meal at low levels could bring about good results but more experiments are required for verification of the precise levels and forms of supplementation. PMID- 8197725 TI - [Auditory evoked brain stem potentials in the diagnosis of disseminated demyelinating processes of the central nervous system]. AB - The results of auditory evoked potentials of the brain stem of 109 patients with different clinical form of multiple sclerosis have been analysed. Pathologic findings were classified into five stages. The subclinical lesions at the level of the brain stem were found in 62% of patients in early, monosymptomatic phase of the disease. This method provides a large contribution to early detection of multiple sclerosis. PMID- 8197727 TI - [Indicators of hospital treatment and the organization and management of injuries and diseases in armed combat in 1991 and 1992]. AB - Efficiency of organisation of management of the injured and diseased in combat operations in 1991/2 and results of hospital treatment are studied. The questionnaire was established for collection of data about stationary treatment of the wounded and diseased in 7 military and 15 civilian medical institutions. Data about 9.243 injured of whom only 5.57% were civilians are especially analysed. In most cases injuries were inflicted by mine-explosive devices (48.77% in combat and 6.27% in non-combat operations), then those inflicted by bullets (38.58% in combat and 8.02% in non-combat operations). Self-inflicted injuries occurred in 5.79% in combat and 10.32% in non-combat operations. Injuries inflicted in non-combat operations were found in a high percentage (46.60). They mostly occurred in the open air (41.26%). Injuries of extremities are predominant (64.70%), then injuries of the head and neck (17.90%), thorax (9.90%), abdomen and pelvis (7.50%). Young men (20-24 years old) were commonly injured but the older ones (over 40 years) have been also frequently injured (18.30%). Evacuation of the wounded and diseased was performed mainly by ambulances (about 60%) or helicopters (16%), especially to the medical institutions far in the country (to M.M.A. up to 60%). The first aid was given within the first ten minutes after injury in 55.00% and within 30 minutes in 65.58% of cases. Mutual aid was most frequently applied (33.12%) and then first aid given by general practitioners (32.12%). Surgical treatment was provided one hour after injury to every fourth wounded (24.08%) and after six hours to more than one third of the wounded (31.88%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8197726 TI - [Eicosanoids in septic shock in rats]. AB - In order to evaluate the role of eicosanoids in pathogenesis of septic shock, the dynamics of TxA2, PGE2 and peptidoleukotriene contents has been measured in the liver of rats with surgically induced septic shock (sesum resection). In the same time the general parameters have been followed up: survival, body temperature, hematocrit and glucose contents in the plasma of experimental animals. Aiming to differentiate the importance of some eicosanoids, immediately after surgery methyl prednisolone (phospholipase A2 inhibitor) or indomethacin (cyclooxigenase enzyme inhibitor) have been given. Based on own results the authors have concluded that in pathogenetic mechanisms of septic shock the main role have peptidoleukotrienes, lipooxygenase products of degradation of arachidonic acid. PMID- 8197728 TI - [The effect of thrombocytes on active forms of oxygen generated by leukocytes in the blood of patients with bronchial asthma]. AB - This study was undertaken to evaluate effects of platelets on leukocyte generated active oxygen forms (LGAOF) in blood of patients with bronchial asthma (BA). Twenty patients with BA were studied. LGAOF were studied by the method of luminol dependent chemoluminescence (LC). The basic parameter of CL intensity and delta changes of its peak after addition of platelet enriched plasma or platelet deficient plasma has been measured. In patients in the state of deterioration it has come to decreased parameters of the platelet inhibitory activity compared with healthy volunteers when it has been observed its direct dependence on severity of the deterioration and severity of the disease. In patients in the phase of remission the parameters of platelet inhibitory activity were increased compared to the phase of deterioration, although it was for 1.5 time under normal value. In patients with BA in the phase of deterioration the protective effects of platelets are considerably reduced and LGAOF are intensified which points to the pathologic role of platelets in the oxidant-antioxidant system. PMID- 8197729 TI - [The antiphospholipid syndrome in systemic connective tissue diseases]. AB - The aim of the study was to prove the incidence of antiphospholipid syndrome (APS) in systemic connective tissue disease (SCTD), especially in systemic lupus erythematosus (SLE) and to find out serologic markers of APS. Of 94 patients with SCTD followed up in the last three years 80 had SLE, 7 Sjogren's syndrome, 3 systemic vasculitis, 2 combined systemic connective tissue disease, 1 rheumatoid arthritis, 1 Sjogren's syndrome with vasculitis. Antiphospholipid antibodies (ApSt) were determined by ELISA method. In 31 of 80 patients with SLE (38.07%) antiphospholipid antibodies were proved. In lo of 31 (32.26%) signs of systemic lupus or the presence of APS markers have not been found, while 21 of 31 (67.74%) had some of clinical manifestations of APS (most commonly thrombocytopenia or vascular thrombosis) with evolution of the basic disease. Among our patients with SLE the most common finding was IgG antibody isotype-in 14 or 66.66% of cases. In 5 of 7 patients with Sjogren's syndrome ApAt were proved without clinical evolution of the basic disease and APS. Only 2 of 7 patients of this group showed, together with more increased ApAt, mild evolution of the basic disease and manifestation of APS (livado reticularis and recurrent venous thrombosis). PMID- 8197730 TI - [Acute renal insufficiency in patients after surgical treatment of dissecting aortic aneurysm]. AB - The retrospective analysis was performed of 26 patients (5 women and 21 men), mean age of 47.04 years, surgically treated for aortic dissecting aneurysm (ADA) at the Clinic of Cardiosurgery of the M.M.A. in the period 1988-1990. In the postoperative course acute renal insufficiency (ARI) has developed in 13 (50%) patients: of milder form in 5 (38.4%), medium in 6 (46.1%) and advanced form in 2 (15.3%) patients. The most common precipitating factor in development of ARI has been arterial hypotension (92.3%). In all patients including the patients treated by hemodialysis, it has come to complete recovery of renal function. PMID- 8197731 TI - [Epidemiologic characteristics of collisions and injuries in traffic accidents in the area of Nis]. AB - The epidemiologic picture of the injured in traffic accidents in the Nis region in the last five years (1998-1992) is presented. The analysis was performed of number, types, causes and consequences of traffic accidents with injured and killed people. Traffic accidents most commonly occurred in May and August, during weekends (Friday and Saturday) between 16 and 20 hrs and in the etiology dominated the human factor. These traffic accidents most often cause injuries of the locomotor system, craniocerebral damages and polytrauma. The first on the list of fatalities are drivers of vehicles. The transport of the injured to medical institutions most commonly is inadequate (civil vehicles). Owing to these facts it is necessary to undertake urgently adequate preventive measures in order to reduce the number of traffic accidents and more effective management of the injured. PMID- 8197733 TI - [Chlamydia trachomatis and acute pelvic inflammatory disease]. AB - The incidence of Chlamydia trachomatis infection in women with acute pelvic inflammatory disease has been studied. Chlamydia trachomatis was isolated in 20 (35.71%) of 56 examined women. In all women with positive isolation, the infection was also confirmed serologically. PMID- 8197732 TI - [Comparative therapeutic effect of bronchodilator aerosols and salbutamol cyclocaps]. AB - In 12 men, atopic asthmatics, the bronchodilator effects have been studied after inhalation of 400 micrograms of salbutamol cyclocaps and bronchodilators in aerosol (40 micrograms of ipratropium bromide, 400 micrograms of fenoterol, 100 micrograms of fenoterol + 40 micrograms of ipratropium bromide and 200 micrograms of salbutamol). Bronchodilators were inhaled in different days at the same time. FEV1 measurements were repeated after 30, 60, 120 and 360 minutes and the values were compared with those obtained prior to inhalation of the drug. Although a better bronchodilator response to salbutamol cyclocaps is statistically insignificant, its longest maintenance make it suitable for the long-term therapy. PMID- 8197734 TI - [The significance of endotoxins in clinical medicine]. PMID- 8197735 TI - [Neurophysiologic aspects of sleep in the human population]. PMID- 8197736 TI - [Pharmacotherapeutic effectiveness of thrombolytic agents in the treatment of acute myocardial infarct]. PMID- 8197737 TI - [Diagnostic and therapeutic approaches in cerebral aneurysms and subarachnoid hemorrhage]. PMID- 8197738 TI - [Tuberous sclerosis]. PMID- 8197739 TI - [Brucella meningitis]. PMID- 8197740 TI - Spinal epidural metastases: a common problem for the primary care physician. AB - Spinal metastases are a common complication of cancer that should be managed quickly and aggressively. Most often from lung or breast cancer (or due to lymphoma), they usually seed from blood into vertebrae and extend into the epidural space. The most common presentation is pain and weakness, and the evolution can be rapid with paraplegia within days. Better prognosis is related to slower onset and pretreatment motor status, so spinal metastases are an emergency. Testing includes X-rays, neuroimaging, myelogram/CT and most recently MRI. Treatment is guided by the severity of neurological deficits, whether compression is by soft tissue or bone, and the presence of instability. A soft tissue mass with only mild to moderate deficits can be treated with radiation. Surgery is required for severely affected patients who are deteriorating rapidly with instability and bone in the canal. New approaches and fusion techniques facilitate decompression and stabilization. PMID- 8197741 TI - Geophagia in a chronic hemodialysis patient. AB - Geophagia, the deliberate ingestion of earth, is a serious clinical problem, particularly for dialysis patients. This article presents a geophagic patient with end stage renal disease and reviews the etiology, consequences and treatment of this disorder. PMID- 8197742 TI - Saving big dollars. PMID- 8197743 TI - The new physicians--kill or cure? PMID- 8197744 TI - Practice satisfaction among young West Virginia family physicians. AB - Young family physicians, those in their first five years of practice, were surveyed to determine their satisfaction regarding various aspects of their practices. A total of 67% of the physicians surveyed responded and the results indicated that most family doctors located in communities where there was a perceived need for their specialty. The survey also showed that two of the most important factors necessary to attract and retain family doctors in rural practice are enhanced third-party reimbursement and the availability of other family physicians to share call. This study underscores the necessity to know and understand the sentiments of West Virginia family physicians in order to attract more newly-trained doctors into rural practice. PMID- 8197745 TI - Intraoperative use of rtPA for subarachnoid hemorrhage. AB - Intraoperative thrombolysis with recombinant tissue plasminogen activator (rtPA) was performed in 15 patients with aneurysmal subarachnoid hemorrhage. All patients had significant basal cistern blood accumulation seen on CT scans preoperatively. The patients underwent surgery within four days of subarachnoid hemorrhage with aneurysm clipping in all patients. Postoperatively, transcranial doppler examinations demonstrated reduction in the development of vasospasm to a greater degree in patients treated with rtPA than a similar group of patients managed without the rtPA treatment. Eighty percent of patients receiving intracisternal rtPA had fair to good results compared with 78% of a similar group of patients who underwent surgery shortly after subarachnoid hemorrhage and were not given rtPA. Intracisternal rtPA remains an adjunctive treatment of questionable benefit in the management of patients with aneurysmal subarachnoid hemorrhage. PMID- 8197746 TI - GM 1 antibodies in Guillain-Barre syndrome: isotypes, course and clinical outcome. AB - IgA, IgG, and IgM antibodies against ganglioside GM 1 were investigated in sera of 15 patients with Guillain-Barre syndrome (GBS), as compared with healthy controls. Significantly raised titers were found in 4 patients who showed persisting weakness due to muscle wasting (3 patients) or due to the development of a chronic relapsing form of GBS (1 patient) after a follow up period of 1 year. By contrast, only 1 out of 11 anti-GM 1 seronegative patients showed persisting muscle wasting. In 1 patient with GBS following Campylobacter jejuni enteritis an IgA anti-GM 1 immune response was found to predominate, suggesting that this immune response may be due to crossreactivity between GM 1 and Campylobacter antigens. We conclude that elevated antibody titers against ganglioside GM 1 may be a valuable marker to predict poor motor recovery in GBS. PMID- 8197747 TI - [A new method for measuring central activation: fourier analysis of pupillary oscillations in depressed patients]. AB - While the changes in pupillary size during wakefulness and drowsiness are easy to understand, the origin of pupillary oscillations is quite mysterious. Waves of spontaneous pupillary constriction and dilation accompany periods of increasing sleepiness and spontaneous arousal. Lowenstein et al. (1963) demonstrated that in the dark, the pupils of young normal alert subjects show waves of dilatation and contraction lasting from about 4 to 40 s and measuring up to 0.5 mm. Furthermore, superimposed fast and very extensive oscillations were observed. The first described oscillations seemed to reflect central nervous activation. Therefore we analysed pupillary oscillations during the recording period of static pupillometry (described by the authors in 1992) which lasted for 25.6 s. Before calculating the Fourier analysis, blinks have to be identified and eliminated by means of a new technique which is called "smoothing". Using the Fourier analysis, the spectrum was divided into 5 frequency bands (0.0-0.2; 0.21-0.4; 0.41-0.60; 0.61-0.8; 0.81-1 Hz). We were also interested in the total spectrum. In order to demonstrate utilisation of the new technique, 146 male and female depressed patients (ICD-Diagnosis 296.1, 296.3, 296.1, 296.3 + 300, respectively, 300.4, 301.1, 296.1, 296.3 + 290, respectively), aged between 18 and 45 years, were investigated by means of pupillometry, followed by analysis of pupillary oscillations. The whole group of depressive patients who received antidepressive medication was compared with 64 healthy subjects of similar age to demonstrate differences in the frequency bands.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8197748 TI - [Ergotamine-induced rectal lesions in asymptomatic patients]. AB - Suppositories containing ergotamine can cause anorectal lesions and even fistulae. We therefore carried out prospective investigations on 20 patients (17 female, 3 male) who had been prescribed ergotamine suppositories for migraine therapy. No serious ulceration was found. There was one case of reduced local blood circulation and three patients showed signs of increased blood circulation in the anterior rectal wall. In two further cases we found local hyperemia with minor bleeding. In our opinion anorectal ergotism is a possible, although rare consequence of ergotamine suppository abuse. For longterm treatment alternative routes of ergotamine administration or other groups of substances should therefore be used. PMID- 8197749 TI - [Myoglobinuria and carnitine palmitoyltransferase deficiency. Diagnostic procedure and differential diagnosis]. AB - Carnitine palmitoyltransferase (CPT) deficiency is the most common metabolic cause of recurrent myoglobinuria. We describe five patients with CPT deficiency who were recruited during a 24-months period. Phenotypic expression ranged from mild myalgia without myoglobinuria to severe exercise-induced attacks and a lethal course. The pathophysiological basis of the clinical heterogeneity is discussed. The diagnostic procedure includes a neurological and electromyographical examination as well as an exercise test and extensive biochemical investigations of muscle biopsy specimens. Accurate diagnosis allows an early introduction of preventive measures and clearly improves the outcome. PMID- 8197750 TI - [Diagnosis of lung function in intensive care of newborn infants]. AB - We report our initial experience with pulmonary function testing in neonates during intensive care, using an automated, computerized system (PEDS), which allows non-invasive and rapid determination of pulmonary mechanics and energetics such as compliance, resistance and respiratory drive, and measurement of lung volume (functional residual capacity). This method is used for better physiological characterization and quantification of the respiratory status, to assess the effectiveness of mechanical ventilation and pharmacological therapy, and to guide weaning and extubation. Despite certain limitations with regard to direct evaluation of the respiratory status especially in very sick neonates, pulmonary function testing has contributed to a better understanding of the pathophysiological mechanisms of pulmonary dysfunction and can also be useful to optimize clinical management of neonates in intensive care. PMID- 8197751 TI - [Haemophilus influenzae meningitis 1983 to 1992--epidemiology and sequelae of the disease]. AB - During the ten-year period 1983-1992 40 children (16 girls and 24 boys) were treated for pyogenic meningitis caused by Haemophilus influenzae type b (Hib). The incidence was 1 case per year out of 5500 children younger than 6 years of age. The youngest child was 5.5 months old, 8 children (20%) were younger than 12 months. The highest incidence was during the second year of life (16 patients). The oldest patient was 11.5 years old. The course of Hib meningitis varied. The disease ran a fulminant course in 10 children. In 9 patients the symptoms evolved more gradually over a period of more than 48 hours, whereby 4 of these patients were only slightly ill on admission. Treatment until 1987 consisted of a combination of ampicillin and chloramphenicol, thereafter cetriaxon and ampicillin were used. Two patients died. One child was left with devastating handicaps and 5 children suffer from minor, but persisting sequelae (seizure disorder, delay in psychomotor development, attention deficit hyperactivity disorder, learning problems, speech delay). Transient disorders were found in 8 patients (EEG abnormalities, delay in psychomotor development, transient hearing problems). Severe hearing loss was seen in only one patient. 24 children (60% of all cases) recovered without any sequelae. Our results, in accordance with the literature, show that in spite of prompt availability of medical assistance, potent antibodies and a high standard of hospital care, the mortality and morbidity following Hib meningitis are still unacceptably high. Hence, we emphasize the need to eliminate Hib infection by immunization programmes. PMID- 8197752 TI - Computer determined compliance of the respiratory system (Crs) in ventilated newborn infants. AB - We describe a simple, low cost technique for computerized measurements of compliance of the respiratory system (Crs) by airway occlusion technique in intubated newborn infants. Tidal volumes of 5, 7.5, and 10 mL/kg were injected from a calibrated syringe into the endotracheal tube via a three-way stop cock and a t-piece. Airway pressure was measured by means of a differential pressure transducer. The analog pressure signal was fed into an optically isolated signal conditioning termination panel and an analog input board which was connected to the PC bus. The signal was amplified and A/D converted by the input board and processed by the digital computer. Crs was determined as the ratio of the injected tidal volume to the difference between the endexpiratory pressure and the pressure at airway occlusion. The software is written in Turbo Pascal (Borland Int.) and includes a patient data base and facilities for system configuration, calibration of transducers, data acquisition, handling, calculation of Crs, reporting and archive storage. Data sampling frequency may be individually set at 60 to 200 Hz. Synchronous measurements in 10 newborn infants using analog pressure amplification and polygraphic recording showed that pressures were correctly determined by the computer and that amplitude and frequency response of the pressure recordings were adequate. PMID- 8197753 TI - Elevated levels of lipoprotein (a) in children with familial hypercholesterolemia. AB - Lipoprotein(a)[Lp(a)] concentrations and their correlation to total cholesterol (TC), low-density and high-density lipoprotein cholesterol (LDL-C, HDL-C) and triglycerides (TG) were estimated in 20 normal weight children affected with familial hypercholesterolemia (FH) and for comparison in 20 overweight, but otherwise healthy children, matched for sex and age. The mean value of Lp(a) in patients with FH (0.29 g/l, SD = 0.27) was markedly higher than in the control group (0.17g/l, SD = 0.19), but the difference was not statistically significant. However, the frequency distribution of Lp(a) in both groups was different: the proportion of Lp(a) levels above 0.60g/l was significantly greater in patients with FH than in the controls (p < 0.05). These results indicate that even pediatric patients with FH have increased Lp(a) levels. Since Lp(a) elevation above 0.25 to 0.30g/l--in particular in combination with increased LDL concentrations--is is associated with a markedly increased risk of coronary heart disease, cervical atherosclerosis and cerebral infarction, it seems very important to detect these high-risk individuals as early as possible and to treat them appropriately. PMID- 8197754 TI - [Innsbruck results of bone marrow transplantation in treatment of hematologic neoplasms and solid tumors]. AB - 87 patients underwent bone marrow transplantation (BMT) in Innsbruck between 1983 and 1992. 81 patients were suffering from hematologic malignancies and severe aplastic anemia and six patients had advanced solid tumours/sarcoma. 56% of the patients undergoing HLA-identical sibling BMT were in an advanced or refractory stage of disease at the time of BMT. 19 patients underwent autologous BMT and 5 patients received a graft from an HLA-matched unrelated donor. Patients were treated with standard conditioning regimens according to the underlying disease. Cyclosporine A (CsA) was given prophylactically against graft-versus-host disease (GVHD) either alone or in combination with methotrexate. Probability of survival for patients transplanted in the first chronic phase of chronic myelogenous leukemia (CML) was 85%, whereas the disease free survival (DFS) for patients transplanted in accelerated phase or blast crisis was only 40%. DFS for acute myelogenous leukemia (AML) in first complete remission and acute lymphoblastic leukemia (ALL) standard-risk (i.e., first or second complete remission) was 71% and 60%, respectively. All patients transplanted for non-Hodgkin's lymphoma (NHL) or Hodgkin's disease had refractory or advanced disease. Probability of survival for lymphoma patients was 60%. Acute GVHD > grade II developed in 35% of patients undergoing HLA-identical sibling BMT (46% in the high-risk group vs. 21% in the standard-risk group). Main causes of death in the high-risk group were relapse (31%), severe bacterial or fungal infections (17%), interstitial pneumonia (11%) and acute GVHD (6%). PMID- 8197755 TI - [Determination of serum pepsinogen I and II for assessment of gastroduodenal tolerance of S(+) ibuprofen]. AB - Therapy with non-steroidal anti-inflammatory drugs often causes gastroduodenal side effects. Changes in the gastric mucosa were studied by determination of serum pepsinogen I and pepsinogen II by the means of radioimmunoassay. 41 patients with degenerative rheumatic diseases were divided into two groups, 21 patients receiving 600 mg S(+) ibuprofen daily (3 x 200mg) and 20 patients receiving 900 mg S(+) ibuprofen daily (3 x 300 mg) over a 14-day period. No significant increase occurred in mean and median values of pepsinogen I and II. Indeed, no changes in serum pepsinogen I and II were noted in 80% of the patients in the higher dosage group and in more than 90% of the lower dosage group. None of the gastroduodenal side effects frequently reported during therapy with non steroidal anti-rheumatic drugs occurred. PMID- 8197756 TI - ["Cochlear implants for children"]. PMID- 8197757 TI - [Criteria and procedures for selection of children with acquired or congenital deafness for cochlear implants in Europe]. AB - The Nucleus Mini System 22 cochlear implant has been implanted in over 2,000 children worldwide. Selection criteria have evolved similar to that for adults since implantation in children began in 1985. The appropriate selection of children for implantation is made by a professional pediatric team which considers audiological and non-audiological issues in determining if the child is a cochlear implant candidate. The main philosophy is to establish if the child has the potential to benefit from a cochlear implant. PMID- 8197758 TI - [Preoperative diagnosis in children with congenital and acquired deafness with reference to cochlear implants]. AB - Total deafness in children can be covered with cochlear implants. There are only few general guidelines which have to take into considerations. We have not the same diagnostic tools available like in adults. More than in adults an individual decision has to be made in children. To provide children with an intracochlear multichannel device it has to be organized a sufficient working system of rehabilitation. PMID- 8197759 TI - [Test results in European children with a Nucleus Mini System 22 cochlear implant]. AB - Over 600 European children have been implanted with Nucleus Mini System 22 Cochlear Implant since 1985. As well as its proven safety und effectiveness it has become increasingly important to monitor the benefit provided postoperatively at regular intervals. The results from 144 European children randomly selected suggest that postlingually deafened children show rapid improvements in performance whilst children deafened before acquisition of speech and language progress at slower but a continuous rate in the first years of experience. PMID- 8197760 TI - [History of the development and functional description of the Nucleus cochlear implant]. AB - For deaf children and adults who derive no significant benefit from conventional hearing aids the cochlear implant (CI) has become a clinically accepted alternative. More than 7,000 people worldwide, including over 2,000 children, have received the 22 channel Nucleus Mini System during the last decade. The functional principle of the CI is the translation of acoustic sound signals into electrical impulses for direct stimulation of the hearing nerve. The middle ear and the damaged sensory organ of the inner ear are completely bypassed. The function of the healthy ear is replaced by a microphone, an electronic speech processor, and stimulation electrodes. Approximately two thirds of the postlingually deafened CI users achieve open set speech understanding without lipreading through the Nucleus implant. The Nucleus system is a programmable digital device and is continuously being improved in terms of both performance and ease of use. It is the only CI system with FDA approval for use in both adults and children from 2 years of age. Over 100 European clinics in more than 20 countries are carrying out successful CI programs with the Nucleus device in compliance with strict pre- and postsurgical diagnostic and rehabilitative guidelines. In Austria it was introduced to the Landeskrankenanstalten Salzburg in 1992. A successful program, including specialized rehabilitation, is carried on in close cooperation with the world's largest Cochlear Implant Center in Hannover, Germany. PMID- 8197761 TI - [Pedagogic aspects of rehabilitation of children with a cochlear implant. Report from the Hannover Cochlear Implant Center]. AB - As we see it cochlear implant for deaf born and for children who became deaf is only justified if the cochlear implant center can belay an interdisciplinary teamwork preoperatively and the securing of habilitation respectively rehabilitation. The cooperation between parents and teachers of the children is absolutely necessary. As the neurophysiologists see it the cochlear implant is a good chance for young deaf born children to use sensitive phases for development of hearing and speech abilities. In these phases the children needs adequate stimuli for development. The changes for developing open speech abilities are slight, if the children are older. PMID- 8197762 TI - [Cochlear implants for children: technological prerequisites and practical experiences in audiologic rehabilitation]. AB - Prerequisites for the use of cochlear implants in children are technical reliability and safety of the devices as well as their efficacy in providing useful auditory information. The actual state of technology fulfills those requirements which is documented with examples from the literature as well as own practical experiences. PMID- 8197763 TI - [Cochlear implant for children: indications and surgical aspects]. AB - Since the late 80s cochlear implants (CI) have proved to be an efficient means to help bilaterally profound deaf patients. The CI is supposed to replace the function of the inner ear. A CI-system consists of an externally worn speech processor and the implants itself with intracochlear electrodes. A preoperative promontory test serves to differentiate between inner ear deafness and non functioning hearing nerve, but is performed only in the case of adults. In small children results of electrocochleography form the basis for such an assessment. CI-surgery in small children is basically not more complicated than in adults. Whereas cochlear implants in adults are only indicated for late-deafened patients, both small children deafened after having acquired speech as well as deaf born children can learn to understand and develop speech. However, consistent technical and pedagogical rehabilitation is an indispensable prerequisite for success. This is being done in Hannover in a special children like rehabilitation center where children and 1 parent are trained in-house for 12 times once a week. Results are the better, the shorter the duration of deafness, i.e. if children are implanted already during the 3rd year of age, and deafened children - mostly after meningitis - immediately, if possible. Some children even achieve to develop spontaneous speech with elements of dialects and a nearly-unimpaired level of understanding. PMID- 8197764 TI - World progress in surgery--Progress in clinical and basic research on breast cancer. PMID- 8197765 TI - Adjuvant therapy of breast cancer. AB - About 180,000 American women will be diagnosed with early stage breast cancer during 1993. In many of these patients breast cancer is a systemic disease at diagnosis and thus not curable by local treatment alone. The development of optimal forms of systemic adjuvant therapy has been a major area of research for more than 30 years. The two most widely employed types of adjuvant therapy, cytotoxic chemotherapy and tamoxifen, have been shown to improve relapse-free and overall survival in certain patient subsets. This review highlights recent advances in adjuvant therapy of early stage breast cancer and discusses current treatment guidelines. PMID- 8197766 TI - Role of radiotherapy following total mastectomy in patients with early breast cancer. The Closed Trials Working Party of the CRC Breast Cancer Trials Group. AB - Between June 1970 and April 1975 the CRC (King's/Cambridge) Trial for early breast cancer randomized 2800 patients following mastectomy to immediate prophylactic radiotherapy (DXT group, n = 1376) or control (WP group, n = 1424). Although no difference in overall survival has been demonstrated, there is an increase in mortality in the irradiated patients from nonbreast cancer causes beyond 5 years. It is because of an increase in the number of deaths due to new nonbreast malignancies [RR V 1.89 (1.18-3.05)] and to cardiac-related disease [RR = 1.52 (1.01-2.29)]. This increased cardiac death rate may be related to the use of orthovoltage, which has greater scatter. There was a significant increase in risk for those with left-sided rather than right-sided tumors in this subgroup [chi 2 (int) = 5.08; p = 0.02]. Local relapse was significantly reduced in those patients randomized to radiotherapy [RR = 0.44 (0.39-0.51)]. Median survival following local relapse was 1.35 years in the DXT group and 2.66 years in the WP group (logrank p < 0.001). Patients with the first relapse in the supraclavicular nodes had a particularly poor prognosis (median survival: DXT 0.69 years; WP 1.37 years). Almost 50% of patients who have had a recurrence on the chest wall or in the axilla and subsequently died have had disease at the same site at death, regardless of whether they had radiotherapy immediately following surgery. However, the actual number of patients dying with persistent disease is halved by the use of prophylactic radiotherapy (DXT 66; WP 143). Classic pathological features such as tumor size, tumor grade, and nodal involvement help define those patients at high risk of local failure who should be recommended for immediate radiotherapy. PMID- 8197768 TI - Does the method of management of papillary thyroid carcinoma make a difference in outcome? AB - We have analyzed data on a group of 269 patients with papillary thyroid carcinoma followed on average for 12 years to determine (1) if a prognostic classification scheme can be used to predict an appropriate surgical approach; (2) the effect of treatment on prognosis; and (3) if patients with a "excellent" prognosis benefit from more extensive surgical resection and 131I ablation. Prognostic classification schemes developed by the American Joint Commission, Cady et al., Hay et al., the European Thyroid Association, and our own clinical class scheme each appropriately divided patients into risk category groups. With each system, some patients classified in the low risk group eventually died of the tumor. Considering the excellent but not perfect precision of the prognostic schemes, the need for detailed pathologic analysis, and ideally postoperative thyroid scanning, we conclude that the prognostic classification schemes do not allow the decision at the operating table regarding the appropriate extent of surgery. Patients followed at our institution, operated on by one of three experienced surgeons, and usually given 131I ablation were compared to other patients in the follow-up group operated on by other surgeons and not routinely ablated. There were significantly fewer deaths and recurrences among the patients managed by our method. However, when the groups were restricted to those considering only patients who had more extensive surgery, postoperative 131I ablation, or both, the differences between the groups became insignificant. This finding indicates that the difference in prognosis, comparing patients treated at our institution and those initially treated elsewhere, was primarily due to the routine use of more extensive surgery and postoperative radioactive iodide ablation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8197767 TI - Molecular biology of breast carcinoma. AB - During the last several years basic research has resulted in the identification of many of the factors involved in signal transduction pathways, leading us to a greater understanding of the mechanisms of growth control in breast cancer cells. Many of these factors are the products of proto-oncogenes or suppressor genes. This review describes the role of some of these factors in breast cancer development, progression, and metastasis and discusses implications for future directions. PMID- 8197769 TI - Effects of highly selective vagotomy and additional procedures on gastric emptying in patients with obstructing duodenal ulcer. AB - A solid gastric emptying study was conducted on 46 patients more than 1 year after highly selective vagotomy (HSV) and additional procedures for obstructing duodenal ulcer and on 21 patients after HSV alone for uncomplicated duodenal ulcer. The additional procedures included dilatation (n = 14; HSV + D group), Holle pyloroplasty (n = 14; HSV + P group), and Jaboulay gastroduodenostomy (n = 18; HSV + GD group). The test meal consisted of two eggs labeled with 99mTc sulfur colloid, two slices of white bread toast, and 300 ml of orange juice (total 322 kcal). Gastric emptying curves and emptying parameters (t1/2, half emptying time; lag phase, TLAG; emptying rate, k; and beta value) were compared with those of 17 healthy volunteers, the normal control group. The patients after HSV alone had an almost normal gastric emptying. The HSV + D group showed a significant delay from minute 45 to the end of the emptying curve, corresponding to a longer t1/2 (p = 0.02), and a slower emptying rate (p = 0.029). The HSV + P group approached a nearly normal emptying curve, corresponding to an insignificant difference in emptying parameters. The HSV + GD group had significantly faster emptying from minute 15 to the end of the emptying curve, corresponding to a faster t1/2 (p = 0.0005), a shorter lag phase (p = 0.027), and a faster emptying rate (p = 0.021). Recurrent ulcerations were noted in one patient (4.8%) of the HSV alone group, five (35.7%) of the HSV + D group, one (7.1%) of the HSV + P group, and one (5.6%) of the HSV + GD group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8197770 TI - Elective laparoscopic appendectomy in patients with familial Mediterranean fever. AB - Familial Mediterranean fever (FMF) also known as hereditary polyserositis, is an inherited disorder commonly found in Armenians, Turks, Arabs, Balkans, and Jews originating from North African countries. The diagnosis of FMF is based on clinical findings and family history, as no specific diagnostic test is yet available. One of its main clinical features is recurrent acute episodes of peritonitis. During such an episode, physical examination and laboratory findings may be similar to those for acute appendicitis. Therefore up to two-thirds of FMF patients undergo emergency appendectomy, with the appendix being normal in most cases. As laparoscopic appendectomy has proved to be safe and advantageous, and to prevent misdiagnosis and unnecessary emergency surgery, we performed elective laparoscopic appendectomy in 13 FMF patients ranging in age from 8 to 32 years. They had been suffering from the disease for 1 to 12 years (mean 3.8) and had had an average of 3.5 yearly episodes of FMF peritonitis. All procedures were concluded by laparoscopy without conversion to open surgery. The average postoperative hospital stay was 3.07 days. The only complication was superficial wound infection in one patient (7.6%), and the mean time to regain full normal activity was 8.5 days. We conclude that elective laparoscopic appendectomy in FMF patients is safe. It helps to exclude appendicitis as a cause for peritonitis in these patients and may prevent unnecessary emergency surgery. PMID- 8197771 TI - Doppler analysis of hepatic blood flow predicts liver dysfunction after major hepatectomy. AB - In 17 consecutive patients who underwent major hepatic resection, 9 of whom with combined resection of the gastrointestinal tract or the pancreatic head (or both), postoperative hepatic blood flow was investigated. In this study, the patients were classified into two groups according to their postoperative serum total bilirubin level: Group A comprised 7 patients with the level higher than 7 mg/dl for more than 1 week postoperatively, and group B comprised 10 patients who did not meet this criterion. For 2 weeks after surgery, the portal blood flow velocity, the hepatic artery resistive index (RI) calculated from the changes in Doppler frequency shifts, and the hepatic venous blood flow velocity were measured intermittently using color Doppler ultrasonography. Liver volume was assessed by computed tomography to provide the restoration. Significant differences in portal blood flow velocity and hepatic artery RI were noted between the two groups from the third postoperative day. In group A the portal blood flow velocity decreased below the preoperative value, and the hepatic artery RI increased above 0.75. In contrast, group B showed high portal blood flow velocity and low hepatic artery RI. In both groups the RI correlated significantly with the total bilirubin level (r = 0.74; p < 0.0001), and the growth rate of the remnant liver was proportional to the mean postoperative portal blood flow velocity (r = 0.70; p = 0.016). We concluded that measurement of the portal blood flow velocity and hepatic artery RI can be useful for predicting postoperative liver dysfunction and liver regeneration after major hepatic resection. PMID- 8197772 TI - Continuous hyperthermic peritoneal perfusion for the prevention of peritoneal recurrence of gastric cancer: randomized controlled study. AB - We performed continuous hyperthermic peritoneal perfusion (CHPP) or continuous normothermic peritoneal perfusion (CNPP) combined with cisplatin (CDDP) 300 mg/kg and mitomycin C (MMC) 30 mg/kg in an attempt to prevent peritoneal recurrence after surgery for gastric cancer. Twenty-two patients were treated with perfusion using about 10 liters of saline heated to 41 degrees to 42 degrees C (CNPP group); 18 patients were treated with saline heated to 37 degrees to 38 degrees C (CNPP group); and 18 patients underwent only gastric surgery without perfusion (control group) in a randomized control study. There were two deaths (9%) due to peritoneal recurrence in the CHPP group, four (22%) in the CNPP group, and four (22%) in the control group. The 1-, 2-, and 3-year survival rates were 95%, 89%, and 68%, in the CHPP group; 81%, 75%, and 51%, in the CNPP group; and 43%, 23%, and 23%, in the control group, respectively. There was a significant difference between the three survival curves by the log-rank test (p < 0.01). This difference showed that CNPP and CHPP are both effective procedures for preventing peritoneal recurrence. The maximum concentrations in the perfusate of total and free CDDP with 300 mg administration were 12.2 and 10.1 micrograms/ml, respectively, at the end of the perfusion, and the maximum concentrations of total and free CDDP in plasma were 2.1 and 1.0 micrograms/ml, respectively. The maximum concentrations of MMC in perfusate and plasma with 30 mg administration were 1.00 and 0.05 micrograms/ml, respectively, which are intraperitoneally cytotoxic but systemically safe concentrations. PMID- 8197773 TI - Hereditary breast cancer and family cancer syndromes. AB - Hereditary breast cancer (HBC) shows extant clinical and genetic heterogeneity. Clinically one finds the onset of breast cancer at an early age, an excess of bilaterality, and patterns of multiple primary cancer such as combinations of breast and ovarian carcinoma in the hereditary breast-ovarian cancer (HBOC) syndrome. In addition to HBOC, one sees a variety of putative breast cancer-prone genotypes inclusive of hereditary site-specific breast cancer, and the Li Fraumeni (SBLA) syndrome that is characterized by cancers involving all three germinal layers including sarcomas, brain tumors, leukemia, lymphoma, and adrenal cortical carcinoma in addition to often markedly early-onset breast cancer. Breast cancer is also associated with autosomal dominantly inherited Cowden's disease and autosomal recessively inherited ataxia-telangiectasia. Examples of pedigrees depicting clinical examples of these several HBC syndromes are presented in order to describe HBC's heterogeneity. The recent identification of the BRCA1 gene in early-onset hereditary site-specific breast cancer and the HBOC syndrome has led to new challenges for the genetic counselor. We review genetic counseling, which embraces surveillance and management recommendations that are responsive to the natural history of HBC and address the concept for future development of centers of expertise for HBC in the interest of improving cancer control. PMID- 8197774 TI - Evaluation and management of high risk and premalignant lesions of the breast. AB - Specific, combined histologic and cytologic patterns of atypical epithelial hyperplasia (AH) in the breast indicate a medically relevant risk of breast cancer development in 5% to 10% of women with otherwise benign biopsies. This risk is four to five times that of similar women without such lesions, that is, women of the same age and at risk for the same period of time. These relative risks are not stable and fall 10 to 15 years after detection, more closely approximating the risks of women of comparable age. Proliferative disease without atypia, no matter how extensive or complex, predicts only a slight elevation of risk, which approaches double that of the reference population. There is a strong interaction of AH with family history of breast cancer in at least a first degree relative. This risk doubles the risk of AH alone and is approximately 20% at 10 to 15 years after biopsy, particularly for women in their forties and early fifties. These considerations are of less clinical importance in women over age 60. Low replacement doses of conjugated estrogen after the menopause do not further elevate risk beyond that identified by histologic patterns. Non-comedo ductal carcinoma in situ may be considered a true precursor lesion; however, it differs significantly in many ways from the more advanced lesion recognized as the comedo type of ductal carcinoma in situ. Small examples of noncomedo ductal carcinoma in situ can eventuate in invasive carcinoma after 6 to 10 years. They may be treated by wide local excision without radiation, with no recurrence up to 8 to 10 years in all likelihood. Ductal carcinoma in situ lesions can be extensive within the breast, and this conservative posture should be reserved for smaller lesions. PMID- 8197775 TI - Integration of risk factors to allow patient selection for adjuvant systemic therapy in lymph node-negative breast cancer patients. AB - The selection of patients with axillary lymph node-negative breast cancer who should receive adjuvant therapy today is confused by an expanding arsenal of putative prognostic factors. The size of the primary tumor remains the dominant factor in sorting among this group of patients, with general agreement that tumors 1 cm or less should be spared adjuvant systemic therapy outside of a clinical trial. There are a few favorable histologic subgroups that may be added to this excluded group: ductal carcinoma in situ and pure tubular, papillary, and typical medullary tumors. For the larger tumor (generally > 2 cm in diameter, but always > 3 cm), there is little disagreement that adjuvant therapy is indicated. The host of additional prognostic factors are directed mainly toward the group of tumors that fall between these two categories. Nuclear grade, S-phase, and perhaps p53 mutations influence decisions for treatment by their elevation. Although the decision remains with the patient and the recommendation with the mature judgment of the clinician, the prognostic indicators available continue to multiply. That an indicator can retrospectively sort prognosis is of limited interest. It requires prospective validation in another patient population, reproducibility in other laboratories, and multivariate analysis among factors measured on the same population of patients to integrate a factor into clinical decision-making. It is only beginning to be accomplished. The next generation of factors being sought are those that predict for response or lack of response to specific therapies, rather than merely indicating natural history. Estrogen and progesterone receptors are the prototypes of this class of indicators. PMID- 8197777 TI - Patient selection criteria for conservation surgery versus mastectomy: Memorial Hospital breast service experience. AB - Breast cancer remains the most common noncutaneous malignancy of women. Although the incidence of the disease continues to rise, most women now present with early (stage I or II) disease. Breast conservation has been demonstrated to be equal in efficacy to mastectomy in such patients in six modern-day randomized trials. The utilization of breast conservation has been slow throughout the United States. At Memorial Hospital the utilization of breast conservation almost equals that of modified mastectomy in the treatment of 950+ annual primary operable cancers. Excellent local-regional control can be obtained with a defined surgical approach to the primary tumor and axillary nodes, radiotherapy to the breast with a boost to the primary site, and finally patient selection. PMID- 8197778 TI - Conservative surgery for the management of invasive and noninvasive carcinoma of the breast: NSABP trials. National Surgical Adjuvant Breast and Bowel Project. AB - In 1976 the National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a randomized trial (B-06) to evaluate the worth of lumpectomy in the treatment of patients with stages I and II breast cancer. This report presents, for the first time, findings from that trial through 10 years of follow-up relative to ipsilateral breast tumor recurrence (IBTR), distant disease-free survival, and survival of patients who were treated by modified radical mastectomy, lumpectomy, or lumpectomy followed by breast irradiation. The report indicates that the incidence of IBTR observed in the B-06 trial is decreased by effective systemic therapy as well. Also commented on are a number of issues regarding the use of lumpectomy that are of concern to clinicians. They relate to the need for tumor specimen margins, the size of tumors amenable to lumpectomy, treatment of breast tumor recurrence, lumpectomy in older women, and other concerns. No patient or tumor characteristics have been identified that preclude the use of lumpectomy and radiation therapy. All evidence continues to justify the use of lumpectomy and breast irradiation for the treatment of invasive breast cancer. In addition, we have noted findings that indicate the propriety of lumpectomy and breast irradiation for treatment of localized ductal carcinoma in situ. PMID- 8197776 TI - Management of in situ and minimally invasive breast carcinoma. AB - In situ breast carcinoma represents an early localized stage in the transition to invasive breast carcinoma and has an especially favorable prognosis with appropriate management. The widespread use of mammography has contributed to its increased rate of diagnosis. The two histologic forms of this entity have distinct pathologic and biologic characteristics, with different therapeutic implications. Lobular carcinoma in situ is considered a marker of increased risk for subsequent invasive carcinoma and is most commonly managed by nonoperative surveillance. Ductal carcinoma in situ behaves more as a true anatomic precursor of invasive disease and has the same therapeutic options as invasive breast carcinoma. Minimally invasive breast carcinoma should be considered a fundamentally different entity, primarily because of its potential for systemic metastasis that in situ lesions do not theoretically have. There are still many outstanding issues and dilemmas to be resolved by scientific investigation before the intriguing potential of these early forms of breast malignancy are fully understood. PMID- 8197779 TI - Conservation approaches for the management of stage I/II carcinoma of the breast: Milan Cancer Institute trials. AB - The most recent analysis of the results of three major trials on breast conservation carried out at the Milan Cancer Institute between 1973 and 1988 showed that breast conservation consisting of a wide breast resection (quadrantectomy) plus radiotherapy is a safe procedure, and that there are no differences in long-term survival (up to 19 years) compared with women who have undergone Halsted's mastectomy. The studies also showed that reducing the extent of surgery from quadrantectomy to lumpectomy increases the risk of local recurrence by nearly three times, as does withdrawing radiotherapy. However, in women older than 55 years, quadrantectomy alone (without radiotherapy) may yield good results. Among the risk factors for local recurrence, a young age and the presence of an extensive intraductal component are the most significant. PMID- 8197780 TI - Risk factors and management of local recurrence following breast conservation surgery. AB - Although a number of histologic and treatment factors that individually and in combination predict for an increased risk of local recurrence after breast conserving surgery can be identified, none so obviously compromises survival that breast conservation is contraindicated because that risk factor is present. In breast recurrence is associated with the risk of any disease remaining after lumpectomy if the breast is not irradiated and the risk of large amounts of residual disease if irradiation is used. Some risk factors appear to predict for both local recurrence and distant recurrence, whereas others predict an increased risk of local recurrence but appear to have little effect on the risk of metastatic disease. Overall, the relation between in-breast recurrence and the risk of systemic metastases is poorly understood. Furthermore, the efficacy of chemotherapy in decreasing the risk of systemic metastases after in-breast recurrence has not been evaluated. Mastectomy is the treatment of choice for in breast recurrence after breast conserving surgery and radiation therapy. A few patients are candidates for a second attempt at breast conservation. PMID- 8197781 TI - Management of locally advanced breast cancer. AB - The management of locally advanced breast cancer with single modality therapy has been associated with a high rate of systemic failure. A multimodality treatment strategy that includes induction cytotoxic chemotherapy, surgery, radiation therapy, and, possibly, hormonal ablation therapy is the current preferred management approach. As our knowledge and understanding of the mechanisms involved in mitogenic signal transduction improve, it is likely that less toxic, more efficacious agents will emerge. PMID- 8197782 TI - Management of inflammatory breast cancer. AB - Inflammatory breast cancer (IBC) is a rare but often fatal disease. This review discusses the following conclusions: (1) The diagnosis of IBC is based on the clinical triad of erythema, ridging with peau d'orange, and rapid onset. The importance of histologic evidence of dermal lymphatic involvement is controversial. (2) Combining doxorubicin-containing chemotherapy with mastectomy or radiation therapy improves survival over that achieved with mastectomy or irradiation alone. (3) Mastectomy after induction chemotherapy may not improve survival or decrease locoregional recurrence rates, but the surgery does provide important prognostic information on treatment response and enables use of a lower radiation dose afterward, which results in reduced long-term complications. (4) The optimal number of cycles and dose intensity of chemotherapy for IBC remain undefined. PMID- 8197783 TI - Salvage surgery for recurrence after breast conservation. AB - Breast conservation surgery and radiation therapy are chosen with increasing frequency in breast cancer management. In addition to the risk of developing a contralateral malignancy, these women are at risk for local recurrence or a new primary lesion in the conserved breast. Most of these ipsilateral recurrences can be treated successfully with salvage mastectomy. The prognosis with salvage mastectomy depends on several factors, including the method of diagnosis of the recurrent tumor, the size of the recurrence, the extent of breast involvement at recurrence, the time interval from initial surgery to recurrence, the involvement of axillary nodes at the initial diagnosis and at the time of recurrence, and the histopathology of the recurrent tumor. PMID- 8197784 TI - Evaluation of a sunflower oil used for frying by different analytical indexes and column and gas chromatography. AB - The alteration of a sunflower oil used repeatedly and discontinuously for frying potatoes on 15 successive occasions was studied. For this purpose, standard analytical indexes, such as fatty acids, gas chromatography, refraction and color indexes, and acid value were compared with a chromatographic method that quantifies the polar compounds originated during fryings. Total polar content increased significantly (p < 0.05) from 6.2 +/- 0.3 mg/100 mg oil to 18.7 +/- 0.8 mg/100 mg oil in the last frying. Linoleic acid decreased significantly (p < 0.05) from 53.8 +/- 0.2 mg/100 mg oil to 48.1 +/- 0.8 mg/100 mg oil at the 15th frying, while oleic acid concentration remained unaltered throughout the frying operations. The color index, and acid value, showed a significant increase (p < 0.05) after 15 fryings. Color index, acid value, and total polar content highly and significantly correlated with the number of fryings (0.981 > r > 0.933; p < 0.01). Linoleic acid concentrations also significantly correlated (r = -0.692; p < 0.05) with the number of fryings performed. Acid value, color index, and linoleic acid concentration also showed high and significant correlation with the percentage of total polar component of the oil (r = 0.9272, r = 0.9065 and r = 0.764 respectively; all p < 0.01). These data suggest that standard methods such as acid value and color index can be applied and are as useful as silica-gel chromatographic evaluation in the monitoring of frying operations, provided that initial values of both the color index and acid value are available. PMID- 8197785 TI - [Dietetic influences on the formation and prevention of cholesterol gallstones]. AB - Dietary factors have long been considered to influence the formation of cholesterol gallstones. A number of clinical and epidemiological studies have demonstrated, although with inconsistent results, the possible impact of dietary factors such as high energy intake, high intake of cholesterol and fat (especially polyunsaturated fatty acids), high intake of refined carbohydrates, and low intake of dietary fiber. However, the obvious increase in the prevalence of gallstones in Western countries after the second world war is thought to underline a role of lifestyle and dietary factors. The following review summarizes current information concerning dietary risk factors and their impact on gallstone formation and prevention. PMID- 8197786 TI - [Content of trans-fatty acids in food]. AB - The fatty acid composition of the fat in 197 food samples has been analyzed by gas liquid chromatography. The use of a 30 m capillary column coated with CPSil88 permitted the separation of the cis and trans isomers. The trans fatty acid content of milk and milk products ranged from 1.9 to 7.9%. Meat samples from ruminants contained 2.0-10.6% trans fatty acids. In pork fat the amounts were less than 0.5%. Sausages and other meat products contained high levels of pork fat. Therefore these samples contained less than 1% trans fatty acids, with the exception of some pure beef products. The amounts of trans fatty acids in foods which may contain hydrogenated oils ranged from 0 to 34.9%. In food samples with high levels of trans fatty acids lower contents of saturated fatty acids were analyzed. PMID- 8197787 TI - Mechanism of hypocholesterolemic effect of oyster mushroom (Pleurotus ostreatus) in rats: reduction of cholesterol absorption and increase of plasma cholesterol removal. AB - The content of cholesterol in the serum and liver of male Wistar rats fed, for the period of 8 weeks shortly after weaning, a diet containing 0.3% of cholesterol was reduced by 33 and 27% by the addition of 5% of dried oyster mushroom powder. Although the level of serum triacylglycerols was not affected by oyster mushroom, their content in liver of rats on mushroom diet was reduced by 41%. Very-low-density lipoproteins and low-density lipoproteins participated by 55 and 38%, respectively, in the total reduction of serum cholesterol. Cholesterol content in high-density lipoproteins was not significantly affected by oyster mushroom. Cholesterol absorption as determined by dual-isotope plasma ratio method was significantly reduced by 14% with oyster mushroom diet. Similarly, this diet increased by 42% the fractional catabolic rate of cholesterol determined by the analysis of decay curve of [4-14C]cholesterol. PMID- 8197789 TI - [The effect of vitamin C and zinc on the copper-induced increase of cadmium residues in swine]. AB - In commercial pig fattening, copper is added to the feed in amounts that greatly exceed the requirements of the animals. On the one hand, this improves weight gain, but on the other, as we were able to recently prove, the retention of the heavy metal cadmium rises in the kidney, in the liver and in muscle. In a feeding experiment with female and male castrated piglets, we tried to counter the copper induced rise in cadmium (175 mg Cu/kg feed) by adding zinc or vitamin C to the diet. While addition of 100 or 200 mg zinc per kg of diet had no influence, the addition of 1000 mg vitamin C reduced the elevated cadmium values in the kidneys and livers to values only determined with a low copper supplementation of 35 mg copper per kg of feed. This positive vitamin C effect not only occurs in cases of high copper supplementation (175 mg Cu/kg feed); when the pigs were given only 35 mg copper per kg of feed, vitamin C also reduced the cadmium content in the organs by 35 to 40%. This indicates that vitamin C improves the quality of food gained from animals for human consumption in both conditions. PMID- 8197788 TI - Influence of the consumption of casein, or tuna in the raw, cooked or canned form, on the utilization of iron in the diet of weanling rats. AB - A study was made of the influence of the consumption of white tuna (subjected to various thermal treatments) on the bioavailability of dietary iron. Biological assays were carried out on Wistar rats fed semi-synthetic diets varying only in the protein source, casein-methionine, or tuna provided in the following forms: raw, cooked in brine, sterilized with or without soybean oil, and canned and stored for a period of 1 or 3 years. Feed intake, the fecal and urinary excretion of iron, and the iron content of the liver were monitored. Absorption of iron was enhanced by consuming the diet containing raw white tuna. However, the beneficial effect of raw tuna was greatly reduced by cooking it in brine, and even more so by sterilization, especially in the presence of oil. The benefit was partly restored by storing the conserves for a period of 1 or 3 years. It is hypothesized that structural alterations to the protein caused by thermal processes can affect the solubility and bioavailability of iron. PMID- 8197790 TI - [Dietary fiber intake of a collective of Swiss population interested in nutrition]. AB - From May to November 1991, a dietary survey in form of a 24-h-recall questionnaire was carried out in Zurich. For the first time, food data from a large, voluntary, undefined, selected collective was acquired (n = 3653). The mean dietary fiber intake of the women was 30 g/day and of the men 33 g/day, which is comparable with various literature data. These values show a positive trend in the eating habits of the population. The dietary fiber intake was also considered in relation to the origin of the fibers. PMID- 8197791 TI - [The enteric nervous system as the "little brain" of the gastrointestinal tract]. PMID- 8197792 TI - [Clinical significance of gastrointestinal hormones]. PMID- 8197793 TI - [The EGF receptor and stomach cancer]. PMID- 8197794 TI - [Long-term results of enteral nutrition by percutaneous endoscopic gastrostomy in multi-morbid internal medicine patients]. PMID- 8197795 TI - [Intestinal absorption of calcium in diseases of the endocrine system]. PMID- 8197796 TI - [Angiodysplasia of the gastrointestinal tract: incidental finding or cause of recurrent gastrointestinal hemorrhage?]. PMID- 8197798 TI - [Adjuvant therapeutic procedures in colorectal cancer: indications and possibilities]. PMID- 8197797 TI - [Is pathogenetically-founded therapy of chronic inflammatory bowel disease in sight?]. PMID- 8197799 TI - [Biofeedback treatment of chronic constipation]. PMID- 8197800 TI - [Epidemiology and clinical aspects of chronic viral hepatitis]. PMID- 8197802 TI - [Current themes in gastroenterology. Dedicated to Herrn Professor Georg Strohmeyer on his 65th birthday]. PMID- 8197801 TI - [New aspects on the pathogenesis of genetic hemochromatosis]. PMID- 8197803 TI - [New aspects of the regulation of glucose metabolism in chronic liver diseases]. PMID- 8197804 TI - Association of primary sclerosing cholangitis with inflammatory bowel diseases: a prospective study. PMID- 8197805 TI - [Central nervous system modulation of gastrointestinal functions]. PMID- 8197806 TI - [Therapy of HIV infection with nucleoside analogs]. PMID- 8197807 TI - Cyclosporin for the treatment of severe ulcerative colitis. AB - The effect of cyclosporin was evaluated in six patients with severe ulcerative colitis not responding to at least 8 days of standard therapy with intravenous corticosteroids. Cyclosporin (5-7.5 mg/kg/day intravenously) was added while steroid therapy was continued. Five of 6 patients responded after a mean of 7 days and colectomy was not necessary. After 4 weeks three patients achieved clinical remission or had mild symptoms and were weaned from cyclosporin and corticosteroids without exacerbation within the next 7-15 months. Two patients improved and they were put on oral cyclosporin. One of them relapsed after 2 weeks and then responded to high dose corticosteroids. This patient is doing well at 8 months of followup on azathioprine and steroids. One patient stopped oral cyclosporin after 3 months abruptly and then had a relapse. He subsequently improved while refusing any medical therapy. Side effects of cyclosporin occurred in 2 patients but were mild and self limited and did not necessitate discontinuation of the drug. Cyclosporin appears to be effective in a large portion of patients with severe ulcerative colitis who failed to improve on corticosteroids and in whom colectomy would otherwise be considered. PMID- 8197808 TI - Lactulose or paromomycin do not affect ammonia generation in the isolated perfused rat small intestine. AB - It has been hypothesized that the beneficial effect on hepatic encephalopathy of lactulose or neomycin might be exerted by their effect on intermediary glutamine metabolism and ammonia generation within enterocytes. We examined glutamine consumption and the production of alanine and ammonia (net substrate exchange in nmol min-1 g-1) in isolated vascularly and luminally perfused small intestine from rats with and without pretreatment with lactulose (2.0 g/kg) or paromomycin (60 mg/kg). Without pretreatment, 50 mM lactulose or 1 mM paromomycin were equally ineffective to significantly reduce the consumption of arterial glutamine (-92 +/- 5 vs. -80 +/- 6 vs. -71 +/- 6 for controls, lactulose, or paromomycin; mean +/- SEM, n = 6 each, n.s. by analysis of variance), and the production of alanine (41 +/- 3 vs. 44 +/- 3 vs. 61 +/- 7, n.s.) or ammonia (42 +/- 6 vs. 42 +/ 6 vs. 38 +/- 6, n.s.). Similarly, glutamine utilisation, and the release of alanine and ammonia were not different after pretreatment for 10 days. Also, both agents did not reduce glutamine absorption from the lumen (-170 +/- 9 vs. -171 +/ 6 vs. -219 +/- 25, n = 5 each) or the concomitant vascular release of metabolic products alanine (92 +/- 7 vs. 78 +/- 10 vs. 77 +/- 10 vs. 77 +/- 7, n.s.) and ammonia (73 +/- 6 vs. 69 +/- 7 vs. 65 +/- 8, n.s.). Our results do not support the hypothesis, that lactulose or paromomycin reduce ammonia generation by small intestinal mucosa through a specific effect on intermediary glutamine metabolism. PMID- 8197810 TI - [Yersinia enterocolitica infection with extraintestinal manifestations: case report and overview]. AB - Five weeks after a four-day visit to Malta, a 39-year old white male German national developed septic temperatures of up to 40 degrees C, progressive jaundice and a pronounced hepatosplenomegaly. The initial examination showed a very sick, somnolent patient with jaundice, cyanosis, tachypnea and a markedly enlarged liver on both physical examination and sonography. The laboratory evaluation revealed a moderate leukocytosis, markedly accelerated ESR, poor liver function with strongly elevated gamma-GT and alkaline phosphatase levels. Primary antibiotic therapy consisted of doxycycline. Ultrasound examination of the liver four days after admission revealed multiple hypodense abscesses. On the sixth day after admission, gram-negative rods were first isolated from blood cultures; antibiotic therapy was switched to ofloxacin (2 x 400 mg/day) and amoxycillin (3 x 2 g/day) after sensitivity testing. As a result of treatment with this combination of antibiotics, the patient was free of fever 10 days after hospitalization; on the same day yersinia enterocolitica was isolated from the first blood cultures taken on admission. The diagnosis of non-enteric forms of yersinia infection can prove very difficult, especially if the serology is not clear cut and there are no immunological complications. A presentation including intermittent fever, moderate leukocytosis, strongly accelerated ESR and multiple hypodense abscesses in the liver should lead one to consider a non-enteric type of yersinia infection. Hepatic abscesses usually occur in patients who have an iron overload. PMID- 8197809 TI - Epidemiology of hepatocellular carcinoma. Evaluation of viral and other risk factors in a low-endemic area for hepatitis B and C. AB - To assess whether hepatocellular carcinoma (HCC) in patients with cirrhosis of the liver is associated with particular risk factors, a retrospective, case control study was performed. Eighty-six patients with HCC (90% had underlying cirrhosis of the liver) were compared with 86 controls who had cirrhosis but not hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), and to hepatitis C virus (anti-HCV) were evaluated; and alcohol and nicotine abuse were assessed by history. The prevalence of HBsAg and anti-HBc was similar in both, case and control patients. Antibodies to hepatitis C virus were detected more frequently among patients with HCC and cirrhosis (37%) compared to cirrhosis alone (22%). Alcohol abuse was found more frequently in patients with cirrhosis alone. Smoking habits were comparable between the two groups. None of the tested variables were related to an increased risk for HCC. Using an ordinary logistic regression approach, none of the variables could be identified as an independent risk factor for HCC. However, the combination of hepatitis B virus infection and hepatitis C virus infection was more prevalent in the patients with hepatocellular carcinoma and cirrhosis (48%) when compared to patients with cirrhosis alone (13%) (odds ratio 6.364; CI 1.149-35.229). In conclusion, we failed to identify independent risk factors for the development of HCC in Germany. However, the combination of hepatitis B and C virus infection increases the risk for liver cancer. Molecular analyses have to be performed to elucidate viral hepatocarcinogenesis. PMID- 8197811 TI - [Juxtapapillary intraduodenal lipoma as a rare cause of jaundice and acute pancreatitis]. AB - A 52-year-old man was admitted to hospital with acute pancreatitis and jaundice. The patient's medical history showed a case of hospitalization due to acute pancreatitis about three years before. Diagnostic examinations (abdomen sonography, CT, contrast medium radiography of the small intestine, ERCP) revealed a juxtapapillary lipoma, approximately 1 by 6 cm, obstructing the papilla Vateri. After the examinations had been completed and the pancreatitis had largely eased off, the lipoma was removed by transduodenal surgery. There were no postoperative complications. PMID- 8197812 TI - Gastric antral vascular ectasia: a case report of a 10 year follow-up with special consideration of histopathological aspects. AB - The diagnosis of gastric antral vascular ectasia (GAVE) was made in a 67 year old patient with a ten year course of the disease, which was characterized by non ulcerous dyspeptic symptoms in its early phase. The patient was treated successfully by antrectomy. The morphologic findings in the biopsy material ten to eight years before the operation corresponded with those of gastritis type C. The highly characteristic morphologic findings of sinusoidal capillary ectasia and multiple vascular thromboses appeared only in later biopsies taken during the work-up for iron deficiency anemia. The cause of the mucosal alterations was an acquired submucosal vascular anomaly (malformation). PMID- 8197813 TI - [Mucinous cystadenomas and cystadenocarcinomas of the pancreas--the pancreaticoscopy as a new device for endoscopic and histological diagnosis]. AB - Recent advances in diagnostic imaging procedures offer the opportunity for detection of rare cystic neoplasms of the pancreas. Cystadenomas of the pancreas have been reported to represent 10% of cystic pancreatic lesions. Serous microcystic cystadenoma, megacystic mucinous and duct-ectatic mucinous cystadenoma were distinguished. While the serous cystadenoma is benign, in general the megacystic and the duct-ectatic mucinous cystadenoma have a significant malignant potential. With pancreatoscopy, a rather new endoscopic technique, five cases of mucinous megacystic cystadenoma were diagnosed preoperatively by macroscopic and microscopic means. In one case, development of malignant neoplasm was diagnosed, one patient did not undergo surgery because of her age. Three patients were operated (total pancreatectomy in one case, duodeno hemipancreatectomy in two cases) and are without any further signs of recurrence and free of symptoms in a one year to four year clinical follow-up. PMID- 8197814 TI - Does adequate patient selection reduce the risk of gallstone recurrence after successful extracorporeal shockwave lithotripsy? AB - To determine the risk of gallbladder stone recurrence in these patients, 58 of the first consecutive 61 patients with solitary stones achieving complete stone clearance after ESWL and adjuvant bile acid therapy were included in a prospective study. All patients were observed for at least 12 months following discontinuation of oral bile acids. Twenty-one patients fulfilled our postulated ideal criteria (solitary radiolucent stones between 10-20 mm initial diameter, initial stone density < 50 HU, gallbladder ejection fraction > 70%). The remaining patients (n = 37) fulfilled the criteria of the Munich study group. In patients fulfilling our ideal criteria, stone recurrence was not observed in any patient, while in those fulfilling solely the criteria of the Munich group, five instances of stone recurrence were observed (13.5% [n = 37], p < 0.1). Initial stone count is only one factor influencing the probability of gallstone recurrence following ESWL and discontinuation of oral bile acids. Our data suggest that factors such as low initial stone density at gallbladder CT and good gallbladder function not only accelerate initial stone clearance but also reduce the risk of stone recurrence after ESWL once oral bile acids have been discontinued. PMID- 8197815 TI - [Indications for ERCP in acute pancreatitis]. PMID- 8197816 TI - [Ulcerative colitis: no increased risk for colorectal cancers?]. PMID- 8197817 TI - [Liver function: still no new knowledge]. PMID- 8197818 TI - [The Philippines--harassment has made me strong. Interview by Kaj Nyman]. PMID- 8197819 TI - [Philippines--measles and soldiers are greatest threat to mountain dwellers]. PMID- 8197820 TI - [Does the SHSTF membership support new nursing roles?]. PMID- 8197821 TI - [After 3 years as administrator I can try out something else. Interview by Ragnhild Larsson]. PMID- 8197822 TI - [Brazil: street children in the risk zone for HIV and AIDS]. PMID- 8197823 TI - [With the UN in Bosnia--the snipers were the worst]. PMID- 8197824 TI - [Bilingual patients with dementia need extra support]. PMID- 8197825 TI - [Minerals and amino acids in the grains of the recently cultivated "pseudo cereal" species Amaranthus hypochondriacus]. AB - The mineral elements and the amino acids in seeds of cultivated Amaranthus hypochondriacus were studied. The following conclusions can be made: 1. The contents of minerals in Amaranthus seed are similar to those of wheat and (except of a few elements: P, K) of pea. The habitats of plants, especially the soil conditions effect importantly on minerals. -2. The total amino acid content and mainly the rate of essential amino acids (lysine, arginine etc) are higher than those in seeds of wheat and maize and this fact create the importance of cultivation and utilisation of this plant. The cultivated Amaranthus species have favourable ecological properties (drought resistance, undemanding) too. PMID- 8197827 TI - [Fluorimetric determination of erythromycin residues in foods of animal origin after derivatization with FMOC and HPLC separation]. AB - A high-performance liquid chromatographic (HPLC) method for the determination of the macrolide antibiotic erythromycin in eggs, milk, swine muscle, kidney and liver was developed. The drug was extracted from the matrix with acetonitrile. The raw extract was purified by liquid-liquid partitioning and fractionation by reversed-phase HPLC for additional cleanup. Erythromycin was reacted in a pre column procedure with 9-fluorenylmethylchloroformate (FMOC) to enable fluorimetric detection (excitation 255 nm, emission 315 nm) after isocratic separation on an analytical RP-18 HPLC column. Mean recoveries ranged from 99% at fortification levels of 0.03 mg/kg in egg to 38% at 0.06 mg/kg in liver. With the exception of liver all detection limits were below 0.01 mg/kg and precision for all other matrices and tested concentrations (0.015-0.09 mg/kg) better than 20% (coefficient of variation). PMID- 8197826 TI - Changes in furosine and proteins of UHT-treated milks stored at high ambient temperatures. AB - Changes in furosine, undenatured whey protein content, and proteolysis during 90 days storage at 20, 30, and 40 degrees C of UHT-processed milk were studied. Furosine increased as the temperature and storage time increased. The peptide concentration increased during the storage period, being faster at 30 degrees C than at 20 or 40 degrees C. High-performance liquid chromatographic analysis of undenatured whey proteins showed considerable changes in the shape of the peaks during storage. PMID- 8197828 TI - Aluminium content of soft drinks from aluminium cans. AB - The aluminium (Al) content of soft drinks from Al cans has been measured during 12 months of storage, by the graphite furnace atomic absorption spectrophotometry (GFAAS) method. The results show that the Al content in all soft drinks increased during the whole storage time. This increase was a result of dissolution of Al from the can wall due to the presence of aggressive ingredients in the soft drinks, mainly acids. The Al content rose with increasing acid concentration and decreasing pH value of the soft drinks. The evaluated possible daily intake of Al (0.8 mg) through consumption of these drinks was practically negligible in relation to total daily dietary Al intake, as well as to tolerable daily intake. Thus, soft drinks from Al cans are an insignificant source of dietary Al intake and it appears that the Al intake from this source should not be a cause for concern in regard to Al toxicity for the human body. PMID- 8197829 TI - Determination of organophosphorus insecticides in edible oils and fats by splitless injection of the oil into a gas chromatograph (injector-internal headspace analysis). AB - Direct injection of oil or fat into a moderately heated injector enables performance of a kind of headspace technique in the injector: oil or fat is diluted 1:1 with acetone and injected into a vaporizing chamber at 200 degrees C. Components, for example organophosphorus insecticides, evaporate from the oil film on the insert wall and are transferred into the column in the splitless mode; the oil slowly flows along the wall to the bottom of the insert and is retained there in a kind of a bag. Using a flame photometric detector, detection limits are below 10 micrograms/kg. PMID- 8197830 TI - A simple method of sample preparation for analysis of biphenyl residues in citrus fruit peels by gas chromatography. AB - A simple method of sample preparation for analysis of residues of the fungicide biphenyl in peels of citrus fruits by gas chromatography (GC) is described. The blended peels are macerated after addition of anhydrous sodium sulphate in dichloromethane for 2 h. After filtration the biphenyl is quantified directly without concentration of the solution by GC with a flame ionization detector (FID) or a mass selective detector (MSD) under single ion mass conditions. Due to the simple method of sample preparation and good average recoveries of 98-103% with standard deviations of 1-4% in the concentration range of 1-10 ppm, the method described is reliable for analysis of biphenyl in citrus fruit peels. In order to avoid loss of the relatively volatile biphenyl no evaporation of the extraction solution occurs. PMID- 8197831 TI - [Who benefits from systemic therapy with a reflecting team?]. AB - In an evaluation study we investigated the effectiveness of the reflecting team approach compared to eclectic child psychiatric treatment in an outpatient setting and the indications for each type of treatment. The relationship between treatment outcome and diagnostic data obtained with the Multi-axial Classification Scheme was examined in 22 families treated with the reflecting team approach and in a second group of families matched on all important sociodemographic and diagnostic variables but receiving eclectic treatment. No difference was found between the two groups regarding symptom improvement or changes in family functioning. Regarding satisfaction with treatment, the reflecting team approach was superior to the eclectic modality. In the reflecting team group parental mental disorder and inadequate intra-familial communication (according to the new fifth axis of the Multi-axial Classification Scheme) had a negative effect on outcome. PMID- 8197832 TI - [ICD-10 multi-axial classification]. PMID- 8197833 TI - [Diagnosis of expansive behavior in children: how do different observers assess in various situations?]. AB - The present study addressed the question of the extent to which parental assessment of expansive behavior disorders can be validated by clinical assessment and how both types of assessment are correlated with behavior ratings by trained outside observers. The agreement between these different sources of information was analyzed in an unselected sample of 49 children aged 5 to 11 admitted to our inpatient unit for expansive behavior disorder. Most of the children met the clinical criteria for both attention-deficit hyperactivity disorder (ADHD) and conduct disorder (CD). With regard to diagnoses, there was good agreement between the parents' assessment and the clinical assessment made one week after admission. However, the parents rated ADHD as more severe than the clinicians did. Ratings of the children's overt behavior in two standardized situations (play situation, test situation) by trained outside observers had only weak correlations with the parental and clinical assessments. The only significant correlation was between the clinical assessment of hyperactivity and the behavior ratings. The contribution of the situational variability of the children's behavior to the low agreement between the different sources of information is discussed. Where feasible, multiple perspectives should be taken into consideration. PMID- 8197834 TI - [The value of developmental psychological memory research for assessment and diagnosis of primary learning disorders]. PMID- 8197835 TI - [Management of children with partial performance deficits. Legal prerequisites, deficits, perspectives]. PMID- 8197836 TI - [Research in child and adolescent psychiatry]. PMID- 8197837 TI - A skin care resource nurse program: is it effective? PMID- 8197838 TI - Assessing orthostatic hypotension. PMID- 8197840 TI - Diabetes and aging: a growing concern. AB - Diabetes is one of the most common chronic conditions in the elderly, and its prevalence will increase as the population ages. How we treat and educate the older person with diabetes will have a significant impact on his or her level of wellness. Clearly, the older adult does have specific needs and physical limitations due to the aging process, but in most cases these obstacles can be either treated or compensated for with patience, knowledgeable care, and support. Further study is necessary in the education, care, and treatment of this special population. Particularly, the need for development and testing of teaching strategies and the evaluation of educational material designed to enhance learning in older adults is warranted. PMID- 8197839 TI - Clinical decision-making: the art and science of inquiry in caring for elders. PMID- 8197841 TI - Gamma nail vs compression screw for trochanteric femoral fractures. 15 reoperations in a prospective, randomized study of 378 patients. AB - A total of 378 trochanteric and subtrochanteric femoral fractures were randomized to treatment with Gamma nail (177) or Hip Compression Screw (HCS) (201). After a median follow-up time of 17 (10-27) months, 15 patients needed reoperations; 13 had been treated with Gamma nail and 2 with HCS. 10 patients, all treated with Gamma nail, were reoperated because of a femoral shaft fracture. 5 of these fractures occurred 8 (4-10) days postoperatively and were related to intraoperative complications. The other 5 shaft fractures occurred a median of 2 (1-3) months postoperatively after falls, and may be related to stress concentration at the tip of the solid nail. The lag screw cut out or penetrated the femoral head in 5 patients, 3 of them treated with Gamma nail and 2 with HCS. PMID- 8197842 TI - Cementation pressure in arthroplasty. In vitro study of cement penetration into femoral heads. AB - We analyzed the pressure needed for adequate cement penetration into the human arthrotic hip. 85 holes in 39 arthrotic femoral heads were cemented under predetermined pressures and times after cement mixing. Cement penetration correlated well to both pressure and time after mixing. No correlation to the degree of sclerosis was found. At 0.2 MPa, the average penetration into bone was 2 mm. However, 3-5 mm is considered the minimum depth for good fixation of an implant. To achieve a consistent adequate interdigitation, a pressure of approximately 0.3 MPa is recommended. PMID- 8197843 TI - Periarticular bone in rheumatoid arthritis versus arthrosis. Histomorphometry in 103 hip biopsies. AB - Histomorphologic differences of the periarticular bone in rheumatoid arthritis (RA) and osteoarthrosis (OA) may be of importance for long-term prosthetic fixation. We have evaluated bone specimens, obtained during total hip replacement from an acetabular and a femoral biopsy site, in 42 RA-hips and 61 OA-hips. In both groups the bone turnover was increased in the acetabulum compared to that in the femur. In the acetabulums the total trabecular bone volume was equal, but osteoid volume, osteoid surface, resorptive surface, and the appositional rate were increased in RA. On the femoral side, only the osteoid volume was higher in RA. The increased bone turnover with a greater amount of unmineralized tissue, as well as resorptive activity in the acetabulum, may be of importance for the higher rate of acetabular component migration and loosening after total hip replacement in RA. PMID- 8197844 TI - Short-term ibuprofen to prevent ossification after hip arthroplasty. No effects in a prospective randomized study of 47 arthrosis cases. AB - Heterotopic ossification after hip arthroplasty can be prevented by ibuprofen given 3 months postoperatively. To evaluate the effectiveness of 10 days of ibuprofen treatment we performed a randomized, double-blind, prospective study on 57 patients with primary arthrosis, undergoing total hip arthroplasty. 47 patients completed the study and no effect on the incidence of ossification could be detected. PMID- 8197845 TI - Reversibility of the inhibitory effect of salmon calcitonin on bone resorption in rats. AB - Inhibition of osteoclastic bone resorption has been induced in growing rats with high doses of salmon calcitonin. This effect was evaluated by measuring the perichondrial ring height of the proximal tibial metaphysis. The aim was to assess whether osteoclastic activity resumed after a period of inhibition with high doses of calcitonin. 20 male Sprague-Dawley rats were treated for 21 days with 100 units/kg/day of salmon calcitonin subcutaneously and killed after 0-60 days, together with non-treated controls at 0 and 60 days. Arrest of metaphyseal modeling and increased height of the perichondrial ring at the end of the period of therapy (P 0.002 versus controls) were observed. Recovery of bone resorption was evident 20 and 40 days after withdrawal of calcitonin. PMID- 8197846 TI - Toxic effects of methylmethacrylate monomer on leukocytes and endothelial cells in vitro. AB - The influence of methylmethacrylate monomer (MMA) on the cellular integrity of monocytes, granulocytes and endothelial cells in vitro was investigated. Clinically relevant blood concentrations of MMA (i.e., 5-10 micrograms/mL) were clearly cytotoxic to all cell types studied, as evidenced by the release of lactic dehydrogenase (LD) and 51Cr, and increased uptake of trypan blue (vital staining). Scanning electron microscopic examination of cells treated with 10 micrograms/mL MMA showed marked signs of cytotoxicity after 1 min incubation, and after 30 min the majority of the cells were totally disintegrated. These findings may have clinical bearing on intraoperative cardiorespiratory dysfunction and deep vein thrombosis in MMA-fixed joint replacement surgery. PMID- 8197847 TI - Repair of partial quadriceps tendon rupture. Observations in 28 cases. AB - We operated on 28 patients with partial rupture of the quadriceps tendon. A simple excision of the scar tissue and closure of the tendon gave an excellent or good result in 25 patients. Ultrasonography was useful to confirm the diagnosis. PMID- 8197849 TI - Bone mineral content and fixation strength of femoral neck fractures. A cadaver study. AB - We measured the bone mineral content (BMC) of 21 human femoral autopsy specimens using Radiographic Attenuation Technique (RAT). The specimens were then tested for stiffness in a material-testing machine. Osteosynthesis was performed after medial femoral neck osteotomy, using 1 of 3 different pinning methods: 2 hook pins (LIH), 2 cannulated screws (Uppsala), and 3 cannulated screws (CHP). The specimens were allocated to each method by grouping them in triplets with similar BMC. Cyclic loading at 500-1000 N and 1 Hz was performed during 50 minutes. The amount of axial compression during loading was measured. Finally, loading to failure was done and post-fixation stiffness and ultimate compression strength recorded. With one exception, all cases failed where the BMC was less than 0.4 g/cm2. No differences between the methods of osteosynthesis were found. The fixation strength was mostly dependent on the strength of the bone, i.e., the degree of osteoporosis. PMID- 8197848 TI - T-lymphocytes are not necessary for particulate polyethylene-induced macrophage recruitment. Histologic studies of the rat tibia. AB - Immunological processes involving T-lymphocytes have been implicated in the mechanisms of aseptic loosening of joint endoprostheses. We report the histological reaction of bone to phagocytosable particles of high-density polyethylene (HDPE) in normal and T-cell deficient rats. A bolus of 3 x 10(7) polyethylene particles averaging 4.7 microns in size, mixed in 0.1 mL of sodium hyaluronate, was injected into the right proximal tibia of 10 normal and 10 T cell deficient (nude) Rowett rats from the same litter. The left control side was injected with sodium hyaluronate alone. The animals were killed after 6 weeks. Transverse paraffin-embedded sections stained with hematoxylin and eosin were made of the implant area. On the control side, there was normal bone marrow without evidence of foreign body reaction. On the HDPE side, in both normal and T cell deficient rats, macrophages were found to surround and engulf the particles, with no differences in the histological reactions. We conclude that T-lymphocytes are not necessary for the recruitment of macrophages to sites in which phagocytosable particles of HDPE have been implanted. PMID- 8197850 TI - Biodegradable fixation of ankle fractures. A roentgen stereophotogrammetric study of 32 cases. AB - We performed a prospective randomized study comparing fixation with biodegradable polyglycolic acid (PGA) rods (n 15) or screws (n 17) in 32 selected displaced supination-eversion fractures. Immediate postoperative weight bearing in a walking cast was encouraged. An exact reconstruction of the ankle mortise was achieved in 26/32 ankles. Roentgen stereophotogrammetric analysis (RSA) revealed rather small movements in the ankle mortise during fracture healing. A better stability was achieved by using screws. After 6 months the clinical results did not differ. One case of sinus formation and one with local effusion occurred; both healed without impairing the clinical result. To compare the results with a nondegradable osteosynthesis technique, a reference group of supination-eversion fractures previously operated on with cerclage-wires, staples and pins was used. RSA showed better fracture stability with nondegradable fixation. The clinical results, however, did not differ. PMID- 8197851 TI - Postoperative Tc-scintimetry in femoral neck fracture. A prospective study of 46 cases. AB - 13 men and 33 women with 8 undisplaced and 38 displaced fractures of the femoral neck treated with internal fixation were included in a prospective study of Tc scintimetry performed early (1-3 weeks), as well as after 2 and 12 months. 9 fractures redisplaced and 5 had late segmental collapse. Healing complications were associated with decreased uptake in early and 2-month scintimetry, but the specificity was only 50 percent. With normal or increased uptake, uncomplicated healing of the fracture was predictable with 90-100 percent sensitivity. PMID- 8197852 TI - Nailing and occlusion of the medullary cavity. Flow and mechanical changes in rat femora. AB - 25 rats were bilaterally operated on and the femoral canal nailed, nailed and plugged with silicone or only plugged with silicone after intramedullary nailing. A fourth group was intramedullary reamed without any other intervention. The bones were evaluated after 12 weeks, including flow measurements, mechanical properties and bone dimensions. There were no differences between the groups in total bone or cortical bone blood flow. There were only marginal changes in outer and inner anteroposterior diameters and the area moment of inertia. The maximum bending stress in bones that had been both nailed and silicone-plugged was decreased compared to the other groups, except the nailed bones. In the silicone/nail group, energy absorption was less than in the other groups, except the nailed group. We conclude that modest intramedullary reaming, nailing or plugging of the femoral canal do not change the mechanical properties of the bone, nor do they induce chronic vascular changes in bone. However, when the medullary cavity is filled with both a nail and silicone, mechanical as well as structural changes may ensue. PMID- 8197853 TI - Fixation of canine tendons to metal. AB - For the purpose of developing a method to attach tendons directly to the prosthesis, canine supraspinatus tendons were attached in vitro to a metallic surface, using 3 different fixation devices: a spiked polyacetal washer (Synthes), a spiked soft tissue fixation plate (Synthes), and a newly designed Enhanced Tendon Anchor (ETA), which straddled the tendon with interlocking spikes oriented at a 20-degree angle. 2 methods were used: 1) the tendon was fixed directly to the metallic surface, or 2) a bone block containing the tendon insertion was fixed to the metallic surface. The specimens were tested for initial fixation strength in tension to failure; intact bone-muscle-tendon-bone units were used as controls. Bone block fixations were stronger than direct tendon fixations when the spiked washer or the ETA was used; this was not true of the fixation plate. The ETA was stronger than the other techniques in ultimate strength in both direct tendon fixation and bone block fixation. The soft tissue fixation plate was found to be weaker than the other techniques in bone block fixation. PMID- 8197854 TI - Restoration of bone flow following fracture and reaming in rat femora. AB - In rats, bilateral closed femoral fracture was produced after intramedullary reaming to 1.6 mm on the left side and 2.0 mm on the right side. The fractures were fixed with 1.6 and 2.0 mm steel pins. Radioactive microspheres were used to determine bone blood flow at 30 min, 1 day, 3 days and 9 days after fracture. 8 rats were used to estimate normal bone blood flow, and an additional 8 rats to examine the vascular effects of fracture only. Following fracture, total bone blood flow was reduced to about 50 percent and cortical flow to about 40 percent of that in intact bones. Fracture and reaming to 1.6 mm reduced total bone flow to 40 percent and reaming to 2.0 mm reduced the total bone flow to approximately one third of normal flow. Cortical flow decreased to about one third and one quarter in the 2 groups. On Day 1, total flow was practically normalized in both groups. Cortical flow in the 1.6 mm group was about equal to that of intact bones, while it was about one third of normal flow in the 2.0-mm group, and significantly less than the 1.6-mm group. On Day 3, total bone flow was more than double that of intact bones and cortical flow 3 times greater in both groups. Flow continued to increase to Day 9 when a threefold increase in total bone blood flow and approximately a fivefold increase in cortical flow were found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8197855 TI - Muscle contraction increases the strength of healing tibial fracture in the rat. AB - Tibial fractures in 7-week-old rats were fixed with intramedullary nails. After 25 days of healing the nails were removed and the tibiae loaded in vivo with intact soft tissues until refracture. The animals were tested in three-point anterior cantilever bending either during muscle contraction (n 8) or with relaxed muscles (n 8). Muscle contraction increased the ultimate bending moment by 84 percent, energy absorption by 108 percent, bending stiffness by 21 percent, and ultimate deflection by 49 percent. PMID- 8197856 TI - Depression of bone blood flow after blunt trauma. A fracture study in the adult rabbit. AB - Delayed union of long bone fractures is commonly ascribed to deficient vascularity, but bone blood flow after fractures caused by blunt trauma has yet to be quantified. We have studied blood flow to the tibial diaphysis after such fractures, and compared the results with those found after osteotomy. 24 adult New Zealand White rabbits were studied. Fractures of the tibial shaft were produced under anesthesia by percussion and immobilized in a cast. Blood flow to the tibial diaphysis was measured at 1 and 2 weeks using the microsphere method. Cortical blood flow proximal to the fracture was increased at both time intervals, and distally at 2 weeks. Marrow flow was depressed distally at 1 week. Marrow flows at 1 week and distal cortical flows at 2 weeks were reduced in comparison with osteotomies studied previously. This depression of blood flow response by blunt trauma prompts further investigation of the role of vascular factors in delayed union. PMID- 8197857 TI - Delayed rupture of the thumb extensor tendon. A 5-year study of 18 consecutive cases. AB - 18 consecutive cases of delayed rupture of the extensor pollicis longus tendon were recorded during 5 years; 4 were spontaneous, and 14 after distal radius fracture, most of which were undisplaced or only slightly displaced. 15 cases were operated upon with tendon transfers: 13 had extensor indicis proprius transfer, 1 transfer of the extensor carpi radialis longus, and 1 reoperated with the extensor communis to the little finger as a motor unit. Subjectively, nearly complete satisfaction was reported; all patients were able to elevate the thumb to the level of the palm and full independent index finger movements were noted. In this 5-year-period 4,400 patients with distal radius fractures were treated, giving an incidence of delayed tendon rupture after distal radius fracture of 0.3 percent. PMID- 8197858 TI - A histochemical study of the biceps brachii muscle cross-innervated by intercostal nerves. 6 cases of brachial plexus injuries operated with nerve crossing. AB - Direct nerve-crossing of intercostal nerves from the lateral thorax to the musculocutaneous nerve was performed in 6 patients after spinal nerve root avulsion with brachial plexus palsy. Elbow flexion power was regained well enough to move against gravity and some resistance in all cases. The muscles were examined histochemically 4 (1-9) years after the operation. The intercostally innervated biceps brachii muscle showed motor predominance of slow-twitch Type 1 fiber regeneration much more than that of fast-twitch Type 2 fiber in 5 of our patients. Our study suggests that the motor nerves of slow-twitch fibers may have priority in peripheral nerve regeneration over those of fast-twitch fibers. PMID- 8197859 TI - Opening wedge osteotomy for malunion of the distal radius with neuropathy. 13 cases followed for 6 (1-11) years. AB - 13 patients with malunion of the distal radius after Colles' fractures and electroneurographically verified median nerve compression underwent an opening wedge osteotomy without a simultaneous release of the transverse carpal ligament. 12 patients had reduction of the typical night pain with normal or almost normal sensibility within the first 2 months. In 1 patient a release of the carpal ligament was necessary after 6 months. 6 years postoperatively all patients had acceptable wrist function with normal function of the median nerve in all but one. PMID- 8197860 TI - Multiple malignant fibrous histiocytoma of bone. A case report. AB - A 27-year-old man had tumors in both the femoral and the tibial metaphyses of the left knee. Although histological examination of the biopsy specimens revealed different findings in the 2 lesions, the final diagnosis was malignant fibrous histiocytoma in both. PMID- 8197861 TI - Early failure of hydroxyapatite-coating in total knee arthroplasty. A case report. AB - We observed early loosening of a hydroxyapatite-coated tibial component in a total knee arthroplasty in a randomized study comparing HA-coating with cement fixation. Symptoms of loosening started 8 weeks after surgery. Roentgen stereophotogrammetric analysis revealed stability during the initial 6 weeks followed by a pronounced subsidence up to 6 months after surgery when revision was done. At revision, the HA-coating was found to have separated from the medial part of the tibial component. The synovium was abundant with macrophages and multinucleated giant cells containing HA-crystals. Overloading of the prosthesis and suboptimal quality of the HA-coating was believed to have caused the loosening process. PMID- 8197862 TI - Salvage of a foot by free transplants from the contralateral leg in a 5-year-old. AB - A 5-year-old girl had a traumatic amputation of her left thigh and on the right side loss of the posterior part of the talus and parts of the posterior tibial nerve and artery. These defects were treated with free transplantation of the corresponding part of the talus from the amputated left leg and a vascularized graft from the left posterior tibial nerve and artery. 2 years later the girl was able to walk without crutches, the ankle mobility was good, and so was the sensibility in the sole of the foot. PMID- 8197863 TI - A case of pseudotumor from overgrowth of the fibula. Effect of growth hormone treatment of juvenile arthritis. PMID- 8197864 TI - The Cotrel-Dubousset instrumentation for unstable sacral fractures. Report of 3 patients. AB - We present a new operative procedure using the Cotrel-Dubousset (C-D) instrumentation in unstable sacral fractures, where the vertebral column is dissociated from the pelvis. This technique is based on screw fixation in the ileum and in the first sacral and the fifth lumbar vertebrae or the fifth and fourth lumbar vertebrae, with help of interconnecting rods. 3 patients were successfully treated. PMID- 8197865 TI - The cement-canal prosthesis. A new cementation technique studied in cadaver femora. AB - This report presents the cement-canal prosthesis. Acrylic cement is injected through the prosthesis by means of an integrated drill hole system. A second canal system within the prosthesis allows suction from the cavities, which could form in the mantle during cement injection. In an experimental study using 36 human cadaveric femora, 3 cement implantation pressures (0.5 bar, 1.0 bar and 1.5 bar) were used. A conventional cementing technique served as a control. Compared to the controls, a deeper penetration of bone cement into cancellous bone was found. Increasing cement pressure led to deeper cement penetration. The average depths of the cement layer were 2.2 mm at 0.5 bar implantation pressure, 2.9 mm at 1.0 bar and 3.9 mm at 1.5 bar. A cement mantle without voids was achieved by this technique, whereas control specimens showed a wide variability in cement defects. PMID- 8197866 TI - Nerve root canal decompression. Lumbar perineural venous dilatation as an indicator of its efficacy. PMID- 8197867 TI - Bone perfusion and oxygenation. Animal experiments and clinical observations. PMID- 8197868 TI - Zinc blocks the A-type potassium currents in Helix neurons. AB - The effects of Zn++ on the A-current in neurons of Helix pomatia L. were examined using the current- and voltage-clamp technique. IA was significantly depressed by zinc (Kd = 1.8 mM at -30 mV, nH = 0.6) applied in the perfusate. This depressive effect resulted in a depolarizing shift of the activation curve, associated with reduction of the maximum conductance. Zn++ also caused a depolarizing shift of the steady-state inactivation curve. A dose-response curve for the depolarizing shift of the activation and inactivation curves of IA, as a function of Zn++ concentration, could be fitted by a single binding-site model with an apparent dissociation constant of approximately 1.8 mM. The modulatory action of Zn++ on the A-currents was potential-dependent, being more effective near the resting membrane potential, and decreased with depolarization. In contrast to its effect on IA, zinc caused a slight change in the delayed rectifier K-current but evoked an appreciable attenuation of the leak potassium conductance (Kd = 1.9 mM, nH = 1.1). Zinc suppressed the Ca-currents, too. Addition of zinc caused an increase in the time-to-peak and prolonged the decay time constant of the A-currents in a dose-dependent way (Kd = 1.7 mM, nH = 1.4). In close correlation with the voltage clamp experiments, Zn++ depolarized the studied neurons, prolonged the action potential duration, suppressed the spike amplitude and increased the firing rate. The results show that Zn++ can evoke a depolarizing shift of both the activation and inactivation fates controlling IA. This modulatory effect of Zn++ on gating of IA appears to reflect binding to a specific, saturable site. PMID- 8197869 TI - Deep sensibility of the mystacial pad in the rat and its cortical representation. AB - The cortical representation of the rat's mystacial pad was examined with the aid of evoked field potentials and recording of single cell activity. Mechanical bending of the vibrissae activated the well-known area within the somato-sensory cortex. Electrical stimulation of the mystacial pad with inserted needle electrodes, bi- and monopolarly, caused a widespread activation extending practically to the whole exposed cortex, including visual, acoustic and motor areas (MSS potentials). The evoked field potentials were accompanied by well recordable unit activity, mainly in the upper 1000 microns of the cortical depth. Capsaicin, injected into the mystacial pad on the 8th-10th postnatal day heavily impaired the MSS potentials as recorded at 2 months of age, and only moderately acted on the mechanically evoked potentials. So did also the acutely injected capsaicin. Peak latency of the MSS potentials seemed to be in correlation with the distance from the punctum maximum. The latencies of unit potentials, however, did not show such dependence, they were between 8 and 10 ms. MSS potentials are thought to represent cortical projection mainly of thermo- and nociceptive fibers, which play an important role in the early postnatal life. PMID- 8197870 TI - Difference between male and female rats in vasopressor response to arginine vasopressin. AB - A study was carried out how the sexual difference influences the increase in blood pressure (BP) induced by arginine vasopressin (AVP), and how the binding characteristics of 3H-labelled AVP on membranes prepared from the vascular bed were affected. After the administration of various doses of AVP, a significantly higher BP increase was observed in male rats than in females. The vasopressor effect of AVP was reduced in males following orchidectomy or administration of the antiandrogen cyproterone acetate. The vasopressin (VP) antagonist d(CH2)5Tyr(Me)AVP diminished the BP response to AVP in both sexes. The plasma AVP level was found to be much higher in males than in females, but it was decreased to the level of females after orchidectomy. The density of AVP-binding sites in the aorta membrane preparation was smaller in females, and in orchidectomized or cyproterone acetate-treated male rats than in the control males. The results demonstrate that testosterone upregulates the number of AVP-binding sites, leading to an increase in the pressor response to AVP in the rat vascular bed. PMID- 8197871 TI - Protein kinase C activation in Aplysia neurons by phorbol diacetate: comparison of effects following extracellular or intracellular application. AB - The effects of protein kinase C activation on electrophysiological phenomena of neurons in Aplysia californica ganglions were studied. The enzyme was activated by phorbol-12,13-diacetate applied either extracellularly by perfusion, or by intracellular pressure injection. In both forms of application, an increase in the potential upstroke speed and amplitude as well as a reduction of the depolarization evoked by extracellular acetylcholine application was found. A protein kinase C blocker, H-7, had opposite effects on the action potential. All observed actions of the phorbol ester were consistently faster in intracellular application than extracellular. PMID- 8197872 TI - Effects of intracellularly applied aminopyridine on firing activities and synaptic responses of electrophysiologically identified cell types in the motor cortex of cats. AB - Effects of 3-aminopyridine (3-Ap) applied intracellularly into electrophysiologically identified cortical neurons in the cat motor cortex were studied. Actions on the membrane and firing activity properties, excitatory and inhibitory postsynaptic responses were investigated. Intracellular microelectrode techniques and single electrode voltage clamp methods were used in experiments on anesthetized and chronic nonanesthetized cats. In addition to changes in neuronal excitability and firing activity properties the evoked postsynaptic responses were significantly altered. Augmentation of EPSPs was accompanied by increases of the total duration and amplitude of the second slow component of IPSPs without influencing the early fast IPSP component. It is concluded that most actions of 3 Ap reported here are derived from direct effects of 3-Ap on the postsynaptic membrane. PMID- 8197873 TI - Modification in primary visual cortical activity of rat induced by neonatal monocular enucleation, an electrophysiological and autoradiographic study. AB - Mononuclear enucleation was performed in rats at birth. The animals were raised and from the age of 3 months the evoked activity was tested in the contralateral visual cortex both by mapping of evoked potentials and autoradiography. It was found that monocular enucleation changed the distribution of evoked activity characteristically. The focus of activity shifted laterally and restricted itself to the binocular part of the primary visual cortex (Oc1B), while, in the medial part of it (Oc1M) hardly any evoked activity or labelled neurons were found PMID- 8197874 TI - Biological activities of some new arginine vasopressin analogues containing unusual amino acids. AB - Solid-phase synthesis methods were applied to prepare some arginine vasopressin (AVP) analogues containing L- or D-pipecolic acids or alpha-L-homoproline in position 7, D-Cys in position 6, D-Val in position 4, O-alkylated D- or L-Tyr in position 2 and Pmp [1-(beta-mercapto-beta, beta-cyclopentamethylidenepropionic acid)] in position 1. Antidiuretic, vasopressor, antidiuretic antagonist and vasopressor antagonist activities were measured by biological methods. Antidiuretic effects were observed for all analogues. Pip7-AVPPmp1D-Tyr(Et)2D Val4AVP and Mpa1dGly-NH-CH3(9) AVP had higher antidiuretic activities than that of AVP. None of the analogues exhibited an antidiuretic antagonist effect. With the exception of Pip7-AVP, none of the analogues had a vasopressor effect. Small vasopressor antagonist effects were found for DPip7AVP and Mpa1, DPip7AVP. The pharmacological significance of these new AVP analogues and the relationship between the chemical structure and biological activity are discussed. PMID- 8197875 TI - Ultrastructure of the developing muscle and enteric nervous system in the small intestine of human fetus. AB - The ultrastructural organization and some histochemical characteristics of the enteric nervous system (ENS) were investigated in 10- and 18-week-old human fetuses. In the 10-week-old human fetus immature myoblasts, and mostly neuroblasts were found in the ganglia. Simple, undifferentiated neuropil was observed among neuronal cells. The neuropil generally did not contain synapses; however axosomatic synapse was registered rarely on the surface of certain neurons. Neuromuscular junctions were common, both axons and neurons were in close contact with the sarcolemma. In the 18-week-old human fetus the fine structural characteristics of the intestinal smooth muscle cells were the same as in the adult. Nerve profiles were frequently found among the muscle cells. NADH diaphorase histochemistry revealed the presence of numerous ganglia but solitary neurons still occurred. Differentiated neurons and neuroblasts could be distinguished in the myenteric ganglia. Synapses were often detected in the neuropil. Thick nerve plexuses were frequently found in the proximity of smooth muscle cells, forming "distant" and "close" myoneural contacts. Well-defined fluorescent network and several fluorescent nerve cell bodies were demonstrated by glyoxylic acid. The above organization may provide a satisfactory basis for an integrated peristaltic movement in the gut of the 18-week-old human fetus. PMID- 8197876 TI - A new generation of model systems to study the blood brain barrier: the in vitro approach. AB - After an era of studying the unique permeability properties of cerebral endothelial cells with endogenous or exogenous tracers in vivo, the next generation of blood-brain barrier model systems was introduced, when the conditions for isolating the microvessels from brain tissue and culturing the endothelial cells were established. Recent advances in our knowledge of the blood brain barrier have in part been made by studying the properties and function of cerebral endothelial cells with this in vitro approach. This review summarizes in brief the results obtained mainly from this rapidly growing field. PMID- 8197877 TI - Effect of antioxidant treatment on the myocardium during reperfusion in dogs. AB - Open chest dogs undergoing 30-min occlusion of the left anterior descending coronary artery (LAD), followed by 20-min reperfusion, received silibinin (2 mg/kg body weight), allopurinol (100 mg for two days as pretreatment, 20 mg/kg body weight during ischemia and reperfusion), superoxide dismutase (SOD, 5 and 0.5 mg/kg body weight, starting from the last minute of ischemia over 6 min). Control and treated dogs were comparable with respect to myocardial regional contractile force (strain gauge), malondialdehyde (MDA) and creatinine kinase (CK) levels of sinus coronarius blood samples, heart rate, and blood pressure. Allopurinol and large doses of SOD produced significant improvement in contractility and decreased MDA levels, which might suggest free radical mediated reactions during reperfusion. PMID- 8197878 TI - Aerobic fitness does not influence directly heart rate reactivity to mental stress. AB - Thirty-seven aerobically high and low fit male and female university students, selected on the basis of estimated aerobic capacity, completed a set of hard as well as a set of easy mental arithmetic tasks for 90 seconds in a counterbalanced order with a 10 min rest period between the tasks. Heart rate (HR) reactivity to either task was independent of aerobic fitness level. Although subjectively rated as more challenging, HR responses to the hard arithmetic task were not greater than that seen to the easy task. These results do not support the conjecture that aerobic fitness level may mediate HR response to acute mental challenge. The overall implications of these results are discussed in relation to the literature concerning aerobic fitness and mental stress. PMID- 8197879 TI - The effects of simultaneous alcohol and nickel sulphate poisoning on the cardiovascular system of rats. AB - Two groups of male OFA rats received 10% ethanol and 5% sugar, or 5% sugar in their drinking-water. One half of each group received 5 mg/kg b.w. daily dose of nickel sulphate in 10 ml of physiological saline by gavage, for three weeks, while the other half of the groups received 10 ml physiological saline. Morphological (light and electron microscopic) and haemodynamic (radioactive microsphere method) examinations were performed. It was found, that alcohol caused decreases of borderline significance of the arterial blood pressure and the nutritive blood flow of the heart, while nickel sulphate significantly increased the arterial blood pressure, the vascular resistance of the kidneys, liver and brain, increased TPR in a tendinous way. Following a simultaneous administration of alcohol and nickel considerably increased the arterial blood pressure (statistically interaction at a level of borderline significance) and caused the appearance of swollen mitochondria and dilated sarcoplasmatic reticulum in the ultrastructure of the heart. It is concluded, that 1. pathomechanism of myocardium-damaging effects of nickel sulphate and alcohol is different; 2. nickel sulphate and alcohol together (at least in a certain dose range) increase the arterial blood pressure. PMID- 8197880 TI - The effects of simultaneous alcohol and cobalt chloride administration on the cardiovascular system of rats. AB - CFY male rats received drinking water which contained 10% ethyl alcohol and 5% sugar and were treated with 50 mg/kg daily doses of cobalt chloride for three weeks by gavage. Haemodynamic examinations were carried out using radioactive microspheres. Alcohol caused no significant injury of the structure of the myocardium, while cobalt chloride caused incipient multifocal myocytolysis. Blood pressure and nutritive blood flow of the heart were decreased slightly by alcohol and significantly by cobalt chloride. Alcohol additively increased the effect of cobalt chloride decreasing the nutritive blood flow of the heart. It is suggested, that hypoxia increased by dual exposure is responsible for the aggravating effect of alcohol on the myocardial injury caused by the cobalt salt. PMID- 8197882 TI - Response of serum calcium to administration of 1,25-dihydroxyvitamin D3 in the freshwater carp Cyprinus carpio maintained either in artificial freshwater, calcium-rich freshwater or calcium-deficient freshwater. AB - Freshwater carps (Cyprinus carpio) were injected daily intraperitoneally either with vehicle (0.1 ml 95% ethanol/100 gm body wt), or 1,25(OH)2D3 (5 IU/100 gm body wt) and maintained either in artificial-freshwater, calcium-rich freshwater or calcium-deficient freshwater for 15 days. The specimens were sacrificed on day 1, 3, 5, 10 and 15 after initiation of the experiment and serum calcium levels were analysed. (i) Artificial freshwater: Serum calcium level of 1,25(OH)2D3 treated specimens increases progressively from day 3 to day 5. Thereafter, on day 10 and day 15 the level becomes normocalcemic. (ii) Calcium-rich freshwater: In vehicle-injected fish the serum calcium level increases progressively from day 3 to day 10. On day 15 the level becomes normocalcemic. In 1,25(OH)2D3-treated animals the serum calcium levels increase significantly from day 3 to day 5. The serum calcium level exhibits a slight fall on day 10 and day 15 although the value is still hypercalcemic. (iii) Calcium-deficient freshwater: In vehicle injected specimens the serum calcium level shows a progressive hypocalcemia from day 3 to day 5. Thereafter the level increases thus resulting in hypercalcemia on day 15. In the 1,25(OH)2D3 treated specimens there is a significant increase in the serum calcium level from day 3 to day 10. On day 15 the level depicts a slight decrease. PMID- 8197881 TI - Phospholipids of human thyroid gland. AB - The phospholipids from human thyroid have been identified and determined by two dimensional chromatography. The total amount of lipid phosphorus was higher in pathological thyroids (especially in thyroid with Graves' disease) as compared to postmortem tissue. Insignificant differences in percentage distribution of phospholipids between normal tissue and from patients with Graves' disease and nodular goiter were noted. An increase of phosphatidylcholine and a decrease of phosphatidylinositol and sphingomyelin in pathological thyroids were observed. Physiological role of phospholipids in thyroid gland is discussed. PMID- 8197883 TI - Detection of early membrane and nuclear alterations of thymocytes upon in vitro ionizing irradiation. AB - Some membrane and nuclear parameters of rat thymocytes were studied after in vitro X- or gamma-irradiation with doses of 0.5, 1, 2 and 4 Gy followed by incubation for 0.5 to 4 hours at 21-22 degrees C. Early (within the first 2 hours) distinct functional changes of plasma membranes, i.e. increase in Con A binding, autologous rosette-forming capacity, Alcian Blue-induced agglutination, and a decrease in amount of surface negative charges were observed. Meanwhile, the doses applied did not influence the DNA content, and the proportion of pyknotic nuclei did not grossly differ from that of the time-matched controls. However, an increase in AT-rich DNA component was noted. The radiation-induced changes proved to be transient and dose-dependent. In the whole cell populations no irreversible, death-associated events could be detected under the given experimental conditions. PMID- 8197884 TI - The comparative antiarrhythmic and proarrhythmic activity of a 3,7 diheterobicyclo[3.3.1]nonane, BRB-I-28, and lidocaine in the 1-4-day-old infarcted dog heart. AB - We compared the electrophysiological effects and quantified the antiarrhythmic/proarrhythmic potential of the 3,7-diheterobicyclo[3.3.1]nonane derivative, BRB-I-28 and lidocaine in 15 consecutive postinfarction dogs. Electrophysiologic studies were performed in anesthetized animals, 1-4 days (mean +/- SE = 2.47 +/- 0.36) after the two-stage ligation of the left anterior descending coronary artery. Inducibility of sustained monomorphic ventricular tachycardia (SMVT) was compared in the pre-drug state, and after i.v. lidocaine (3 and 6 mg/kg) and BRB-I-28 (3 and 6 mg/kg) administration. During the control state, SMVT was inducible in 6/15 dogs (40%). After the administration of lidocaine, the rate of the inducible SMVT slowed (353 +/- 91 to 272 +/- 96 beat/min; p < 0.01), but due to the proarrhythmic action of the drug, SMVT became inducible in 13/15 dogs (87%). Sustained reentry was induced after 3 mg/kg lidocaine in 3 dogs and after 6 mg/kg in 4. The mean aortic blood pressure in these SMVTs was 36 +/- 8 mm Hg. After administration of BRB-I-28 (6 mg/kg) SMVT was not inducible in 2/6 and in 4 the SMVT rate was slowed (380 +/- 104 to 208 +/ 105 beat/min; p < 0.005) before termination in 3. In 2 dogs SMVT was induced after BRB-I-28 was given whereas they were non-inducible in the control state (proarrhythmic effect: 13%). Furthermore the hemodynamic state during the SMVTs was more stable after BRB-I-28 (mean aortic blood pressure = 65 +/- 7 mm Hg; post BRB-I-28 vs post-lidocaine, p < 0.001). During sinus rhythm, lidocaine caused a transient lowering of the MBP (105 +/- 17 to 84 +/- 18 mm Hg; p < 0.001), whereas, BRB-I-28, induced a consistent but short-lasting pressor response (98 +/ 18 to 120 +/- 29 mm Hg; p < 0.001) after its bolus injection. The low proarrhythmic activity and the lack of a cardiodepressant action makes this new chemical class of antiarrhythmics worthy of further development. PMID- 8197885 TI - Mechanical response of lizard skeletal muscles to disuse: I. Effect of short-term tenotomization. AB - The gastrocnemius muscles of the reptile, Uromastix hardwickii were tenotomized for seven days according to the method described earlier and their mechanical responses were recorded to study the effect of cessation of proprioceptive impulses on the functioning of these muscles. The parameters measured were isometric twitch and tetanic tensions, time dependent tension parameters and other time dependent parameters of twitch and tetanus records. The isometric twitch and tetanic tensions, their ratios and the rate of rise in twitch and tetanus along with P/ms were found significantly lesser in the tenotomized muscles. The other time dependent tension parameters, i.e. twitch contraction and tetanus half relaxation times and their ratios were however, unaffected as compared to their controls. The duration of active state on the contrary, was significantly reduced in the tenotomized muscles. The tenotomization effects observed on the mechanical parameters are discussed in terms of muscle fiber architecture and the degree/rate of cross bridge interaction in these muscles. PMID- 8197886 TI - Mechanical response of lizard skeletal muscles to disuse: II. Effect of short term denervation. AB - The gastrocnemius muscles of Uromastix hardwickii were used to determine the effects of the absence of neural influence on them. For this purpose, the muscles were denervated for 7 days and were used to record isometric twitch and tetanus. The contraction parameters thus obtained from the denervated muscles were then compared with their own controls. The isometric tensions and time dependent tension parameters were significantly lower in the denervated muscles. The time dependent parameters, peak duration in twitch and duration of active state in twitch were however, found to be unaffected by short-term denervation with the exception of twitch/tetanus half relaxation time ratio, which was significantly higher in the denervated muscles. The denervation effects observed on the mechanical contraction behaviour of the gastrocnemius muscle have been discussed in terms of electrical excitation, excitation-contraction coupling and cross bridge interaction. PMID- 8197887 TI - Self-efficacy, health locus of control, and smoking cessation. AB - This article examines the predictive value of measures of health locus of control and self-efficacy as predictors of outcomes of a widely disseminated, group facilitated smoking cessation program. Outcomes studied were cessation for at least 1 day by the end of the program, end of program smoking status (abstinence), and smoking status at 6 months follow-up. Subjects were 257 participants in the smoking cessation program, of whom 207 made attempts to quit and 126 who were not smoking at the end of the treatment. Both pretreatment self efficacy and health locus of control variables emerged as significant predictors of making an attempt and end of treatment abstinence. Only posttreatment self efficacy predicted maintenance at 6 months. The results indicate the high self efficacy is inversely related to making attempts to quit, but positively related to the success of attempts. The role of Health Locus of Control is complex and needs further investigation. PMID- 8197888 TI - Alcoholics also dependent on cocaine in treatment: do they differ from "pure" alcoholics? AB - Although individuals who exhibit both alcohol and cocaine dependency are seen increasingly in traditional alcoholism rehabilitation settings, their comparability with "pure" alcoholics is unclear. Sociodemographic, psychological, cognitive, and substance abuse status were, therefore, monitored in a group of alcoholics (n = 64) versus a group of cocaine dependent alcoholics (n = 82) on admission and just prior to discharge from 28-day multimodal treatment settings. At admission, cocaine-dependent alcoholics were younger, more likely to be unmarried, have more extensive substance use histories as well as more frequent prior treatments than "pure" alcoholics. Additionally, members of both groups exhibited abnormalities on psychological indices. Both psychological and cognitive indices revealed significant between-group differences which subsequent analyses found to be a confound of the marked age discrepancy between groups. From admission to discharge, scores on both psychological and cognitive indices declined significantly in both groups. Urine assay data revealed a greater tendency for cocaine-dependent alcoholics to relapse during treatment. While the psychological and cognitive data largely argue for the comparability of groups of patients classified as "pure" alcoholics with those who are dependent on both alcohol and cocaine, the latter group may have more difficulty in achieving abstinence during treatment. The interpretability of behavioral indices gathered only at treatment admission is questioned. PMID- 8197889 TI - An evaluation of a multicomponent treatment program involving scheduled smoking and relapse prevention procedures: initial findings. AB - In the current study, 34 smokers were treated in a smoking cessation program that involved either a scheduled smoking procedure, or a minimal contact self-help treatment control. The interval smoking program consisted of baseline, cessation, and relapse prevention phases. During baseline, subjects self-monitored smoking and the total hours spent awake. During a 3-week cessation period, the scheduled smoking group progressively increased their intercigarette interval, thereby gradually reducing their total daily intake of nicotine. Smokers were expected to quit on a target date set at the end of this period. Cognitive behavioral interventions and relapse prevention training consisted of behavioral rehearsal of nonsmoking skills in a relapse prone environment. Control subjects were given the American Cancer Society "I Quit Kit", and provided subsequent discussion of its use. The results showed that 53% and 41% of the scheduled smoking group was abstinent at the 6- and 12-month follow-up points, respectively. Controls averaged only 6% for the same periods. Scheduled smoking may be a useful addition to a multicomponent treatment program and further study appears warranted to determine the saliency of the treatment features. PMID- 8197890 TI - Testing the abstinence violation effect construct with marijuana cessation. AB - It has been proposed that internal, stable, and global attributions for the cause of a lapse following a period of abstinence and concomitant feelings of guilt and loss of control increased the probability of a return to regular substance use. The Abstinence Violation Effect (AVE) hypotheses were tested in a sample of 75 adult marijuana users who reported a lapse into marijuana use following completion of either a relapse prevention (RP) or social support group treatment aimed at abstinence. Results showed that more internal, stable, and global attributions for the cause of the lapse and perceived loss of control were related significantly to concurrently reported relapse. Further, internal and global attributions predicted marijuana use during the subsequent 6 months. Results are discussed in terms of support for the AVE construct, treatment implications, and the failure of the RP treatment to modify reactions to a lapse. PMID- 8197892 TI - Diagnosis and assessment of substance abuse in older adults: current strategies and issues. AB - Alcohol and substance abuse in older adults until recently has received little empirical attention in the literature. However, in light of the increasing number of older adults in the population, clinicians and researchers alike are recognizing the importance of evaluating specific assessment and treatment strategies for such older substance abusers. Because distinctive biological, cognitive, and psychosocial variables appear to be correlated with substance abuse in older adults, evaluation and intervention methods employed with younger cohorts may be inappropriate or ineffective with individuals 55 and over. Our article, therefore, examines these characteristics as they pertain to the unique problems and service needs of the elderly. Relevant diagnostic and assessment strategies are reviewed. Finally, suggestions for future work in this area are outlined. PMID- 8197891 TI - Reliability of the Fagerstrom Tolerance Questionnaire and the Fagerstrom Test for Nicotine Dependence. AB - The purpose of this study was to assess the test-retest stability of the Fagerstrom Tolerance Questionnaire (FTQ) in two samples: (a) paid subjects in an American laboratory; data were collected via telephone screen and subsequently via questions embedded in a written history; and (b) smokers hospitalized for depression in Paris; data were collected via a written questionnaire upon admission and again after 3 weeks of treatment for depression. Reliability data are also presented for a recently revised version of the FTQ, the Fagerstrom Test for Nicotine Dependence (FTND), and compared with FTQ data collected in a subsample of subjects in the American database who received both versions of the questionnaire. Both the FTQ (in both samples) and the FTND proved to be highly reliable. The validity of the scales, using cotinine, number of years smoked, and the "addictive" factor on the Classification of Smoking by Motives questionnaire as criterion variables, was also supported. No relationship between FTQ score and severity of depression was detected in either sample. Internal consistency was somewhat higher for the FTND than for the FTQ, replicating previous findings in the literature. PMID- 8197893 TI - Predicting reduction in tension following alcohol consumption in a stressful situation with the Alcohol Expectancy Questionnaire. AB - The present study was designed to extend the research designed to evaluate the validity of the subscales of the Alcohol Expectancy Questionnaire. Other previous behavioral studies had investigated the Global Positive subscale as a predictor of alcohol effects (Sher, 1985) and the tension reduction scale as a predictor of choosing an alcoholic beverage (Corcoran & Parker, 1991). While Brown, Goldman, Inn, and Anderson (1980) do not distinguish between different classes of expectancies, current theory (see Kirsch, 1985) highlights the distinction between response expectations (expectation of nonvolitional effects, exemplified in Sher's study) and outcome expectancies (expectations for particular reinforcers given a specific behavior, as in Corcoran and Parker's study). The present study was an investigation of the AEQ Tension Reduction Scale as a predictor of tension reduction in a stressful situation. The results do not lend support to the scale as a predictor of effects from drinking alcohol or expecting to drink alcohol. Results are discussed in terms of potential for future research, and theoretical and practical implications for the AEQ. PMID- 8197894 TI - The "medicinal effect": a possible mechanism in the development of severe alcohol dependence. AB - An examination of the change in attractiveness of a flavor subsequent to pairing with recuperation from malaise was undertaken. Forty-five subjects consumed a flavor after the rotation-induced motion sickness at two different intervals. Twenty-four consumed, on three separate conditioning trials, the paired flavor immediately as malaise began to decline (short-delay group), the remainder, when malaise had completely diminished (long-delay group). All subjects also consumed an unpaired flavor the morning after each session. Analysis of variance revealed that the paired flavor was rated as more highly attractive than the unpaired flavor, and this effect was only present in the short delay group. These results were taken as supporting the existence of conditioned flavor preferences in humans and interpreted as a possible learning mechanism in the development of severe alcohol dependence. PMID- 8197895 TI - The effectiveness of same-sex versus opposite-sex role models in advertisements to reduce alcohol consumption in teenagers. AB - The differential effectiveness of same- versus opposite-sex role models in persuading teenagers to reduce alcohol consumption was investigated. Based on an actual set of commercials, four 1-min videos were constructed, in which either boys or girls discuss how alcohol adversely affects either boys or girls. These were shown to either teenage boys or girls, resulting in a 2(Sex of Source) x 2(Sex of Subjects [Ss]) factorial design. Ss rated the credibility of the source, the persuasibility of the message, said how much and how often they drank currently, and whether they intended to decrease their future alcohol consumption. Three studies were conducted, in a coeducational (N = 95), boys' (N = 98), and girls' (N = 102) school, respectively. The overall pattern in the data showed that as predicted, same-sex role models were more effective, and that moderate drinkers were more influenced than heavy drinkers; both findings having implications for teenage health education campaigns. PMID- 8197896 TI - Interviewer effects on self-reported substance use among homeless persons. AB - This study examines respondent editing of survey responses to questions regarding substance use. Previous research has identified several types of interviewer effects that may be associated with respondent editing, including direct and social distance effects. Little is known, however, regarding how these potential effects may influence self-reported substance use behavior. Data analyzed for this study were collected as part of a survey of substance use among homeless persons conducted in Cook County, Illinois. A total of 481 respondents were sampled at random in emergency and transitional shelters, soup kitchens, drop-in centers, and single room occupancy (SRO) hotels. Overall, a direct, gender-based effect was observed, with homeless respondents of both genders more willing to reveal substance use behaviors to male interviewers. Some race- and age-related direct effects were also identified, with White and older interviewers obtaining more reports of substance use. These findings yield important evidence regarding respondent editing of self-reported substance use and have implications for the common practice of demographically matching interviewers and respondents. PMID- 8197897 TI - Alcohol and drug use and sexual behaviors placing runaways at risk for HIV infection. AB - Lifetime and current alcohol and drug use and sexual risk acts were examined among 154 male and 148 female runaways, aged 11-19, predominantly Black and Hispanic, residing at four residential shelters in the New York City area. Most runaways reported alcohol (71%) and drug use (46%), with about a quarter (27%) using either alcohol or drugs at least once a week during the past 3 months. Physical symptoms of substance abuse were reported by 47%; 17% reported addiction. Current substance use was higher among males and Hispanics, and increased with age. Substance use was significantly related to reporting more sexual partners and less frequent condom use. The results suggest that HIV/AIDS prevention programs must target the reduction of alcohol and drug use as well as sexual risk acts. PMID- 8197898 TI - [Onset of demontage in emergency medicine in German emergency service?--A commentary]. PMID- 8197899 TI - [Helicopter in emergency service and expanded rescue work]. PMID- 8197900 TI - [Diaphragmatic ruptures: diagnosis--therapy--results, experiences with 64 patients]. AB - From 1963 to 1993, 64 Patients with traumatic lesions of the diaphragm were treated. 58 Patients were admitted after blunt trauma, 6 Patients after a penetrating trauma. 87.5% of the patients were male with an average age of 37 years. In about 80% of cases other severe traumatic lesions were noted in association. With 64% extremities, 50% abdomen, 47% thoracic cavity and 38% head injuries were concomitant lesions. Due to the association with pelvic fractures (45%) a special diagnostic emphasis on diaphragmatic ruptures is recommended. In 83% the left diaphragm is involved. Over the last years the right-sided rupture of the diaphragm were found in an increasing extent from 3.7% up to 26%. Conventional radiography with gastrographin swallow is still the essential diagnostic tool. Hospital mortality (12%) was mainly influenced by complications of concomitant injuries, i.e. cardio-pulmonary insufficiency, Shock and multi organ-failure. PMID- 8197901 TI - [Importance of proximal femoral fractures in elderly patients. Results of a prospective study of 61 patients]. AB - In a prospective study we found good results concerning postoperative complications (21%), perioperative lethality (3.2%) and lethality during hospital stay (6.5%) after implantation of dynamic hip screws (DHS) in patients with per- and subtrochanteric fractures of the femur. The ability to walk, as well as housing and social care postoperatively and follow-up for at least six months after dismissal demonstrates the importance of these fractures for the elderly. One of three patients needs professional care, 21% at home, 13% in nursing homes. Six months after operation the lethality is nearly 20%, i.e. three times higher than in hospital. These are the essential data for all techniques of osteosynthesis used in patients with these fractures, which could only be documented in prospective studies. PMID- 8197902 TI - [Dens fracture in elderly patients and surgical management]. AB - The problems of surgical therapy in seven patients aged over 70 years are discussed. Clinical and radiological findings as well as operative treatment (anterior transaxial screw osteosynthesis or posterior atlanto-axial arthrodesis) are analysed in detail. Five out of 7 patients treated in this way could be early mobilised. Two patients died on multiorgan failure after an initial uneventful postoperative course (28.6% mortality rate). A stable osteosynthesis was obtained in all cases; a complete bony fusion as could be radiologically demonstrated, occurred in four out of the five survivors. We feel that despite this relatively high mortality rate surgical treatment provides better recovery chances and a higher quality of life to such patients. PMID- 8197903 TI - [Surgical management of acute lateral ligament rupture of the upper ankle joint]. AB - In a retrospective study carried out at the Department of Traumatology of the Hospital of Boblingen 169 patients with recent ruptures of the fibular ligament operated on from 1.1.1991 to 31.12.1992 were asked for a clinical examination with stress radiography. 110 patients underwent this follow-up examination, 7 sent back the questionnaire. 99% of the patients were content with the results of the operation. Most patients see the advantage of a short period in a cast and afterwards tape therapy. PMID- 8197904 TI - [Legal expert assessment of shoulder injuries/general aspects: legal accident insurance and expert references, with evaluation schema]. PMID- 8197905 TI - [Fracture of the pisiform bone]. AB - Fractures of the pisiform bone are rare compared with the other carpalia. Diagnosis is difficult because of the complicated anatomic structure of the carpalia, and is facilitated by detailed clinical findings, special x-ray takes and precise knowledge of the history and course of the relevant accident. PMID- 8197906 TI - [Report of the Biodegradable Implants Study Group]. AB - There is a group for the development and testing of biodegradable implants within the German Section of AO/ASIF-International. After in-vitro screening of various polylactide materials and copolymers a L/DL-polylactide 70/30 was selected. In animal experiments it showed long durability over a period of 9 months and expected degradation afterwards. In clinical experience over more than three years the biodegradable pins with x-ray opaque markers (Polypin) applied for fixation of osteochondral lesions yielded good results and no infections. A multicenter clinical study now includes 57 patients. Polypin is the first biodegradable implant of the AO/ASIF-group. PMID- 8197907 TI - [The eye in atopic dermatitis]. PMID- 8197908 TI - [Dual nature of excitatory amino acids in the vertebrate retina]. AB - Glutamic acid plays an important role as a main excitatory amino acid and also as one of the central metabolites in the central nervous system (CNS). This amino acid also acts as a toxic substance in the vertebrate CNS, including the retina, especially in ischemic conditions. This paper reviews recent advances in retinal research on glutamate metabolism and its relationship with pathogenesis of retinal diseases. Excessive administration of glutamate induces overstimulation of N-methyl-D-aspartate (NMDA) and non-NMDA receptors, and influx of Na+, Cl-, and water to postsynaptic elements, causing lysis and swelling. In hypoxic or ischemic conditions, accumulation of glutamate was observed in most parts of the retina. Morphological and functional changes induced by ischemia could be prevented by preadministration of an antagonist of NMDA receptors. These results suggest that the same pathological mechanism as in the CNS exists in the retina. They also suggest that a new pharmacological approach for treating retinal abnormalities caused by ischemia could be introduced in the ophthalmology clinic in the near future. Abnormality of glutamate dehydrogenase, an important enzyme in the glutamate metabolism, has been reported in patients with spinocerebellar degenerations. Retinal dystrophy was also reported in some of them. Partial deficiency of heat-labile activity of this enzyme has been reported to be profoundly related with those patients with retinal abnormalities. This suggests that not only glutamate itself, but also abnormalities in its metabolic path way might be deeply correlated with the pathogenesis of retinal degeneration. PMID- 8197909 TI - [Tissue of origin of herpes simplex virus type 1 reactivated in tear film]. AB - In the present study, we tried to detect the tissue of origin of herpes simplex virus type 1 (HSV-1) reactivated in tear film after artificial reactivation. The combined treatment consisted of iontophoresis on postinoculation day 35, followed by topical epinephrine on 2 days, after which the rabbits were killed. The ocular tissues and trigeminal ganglia were immediately dissected. Their cell-free supernatants were inoculated on CV-1 (African green monkey kidney cell) monolayers for infectious HSV-1 detection. The percentage of recovery from the cell-free supernatants was 50% (5 out of 10 samples) from the cornea, 0% from conjunctiva or lacrimal glands, and 20% (2 out of 10 samples) from trigeminal ganglia. The percentage of HSV-1 reactivation in the tear film was 50%. No infectious virus was detected from tissues or tear film in the control group. Four eyes showed HSV-1 reactivation simultaneously from the cornea and tear film, but only one eye from the trigeminal ganglion and tear film. These results demonstrate that the cornea might be the tissue of origin of HSV-1 reactivated in tear film. PMID- 8197910 TI - [Low molecular weight heparin inhibits raised intraocular pressure following intracameral administration of sodium hyaluronate]. AB - The effect of low molecular weight (LMW) heparin on increase of intraocular pressure following intracameral administration of sodium hyaluronate (HA) was investigated in rabbit eyes. In each case, the aqueous humor of one eye was replaced with HA and a balanced salt solution (BSS) containing 10.0 IU/ml of LMW heparin, and as a control the aqueous humor of the fellow eye was replaced with HA and BSS containing no LMW heparin. Intraocular pressure was measured for 24 hours following the replacement. As a result, significant increase of intraocular pressure was observed at 6 hours after the injection in the eyes administered HA and BSS. In comparison, no significant increase of intraocular pressure was observed in the eyes injected with HA and LMW heparin. When the concentration of LMW heparin was less than 2 IU/nl or the LMW heparin was heat-deactivated, the HA induced increase of intraocular pressure was not inhibited. The results indicated that LMW heparin inhibits increase of intraocular pressure following intracameral administration of HA possibly by an inhibitory effect on intraocular fibrin exudation, and the increase of intraocular pressure is probably associated with interaction between fibrin and HA. PMID- 8197911 TI - [Protein profiles of normal and organ-cultured human trabecular meshwork]. AB - We determined the protein profiles of the trabecular meshwork (TM) obtained from 14 normal human eyes from individuals of various ages (53 to 76 years) using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and a highly sensitive silver staining technique, which yields 50-100 times greater sensitivity than is achieved with Coomassie Blue. Over 30 protein bands varying in molecular weight from 16,000 to 250,000 were consistently visible, regardless of donor age. Protein profiles of one-eighth human TM obtained from each eye showed a same pattern and those of one-eight organ-cultured human TM during 4 weeks also indicated a same pattern. Protein profiles of the TM from normal human eyes of various ages shared a number of similarities. Protein profiles of the TM, peripheral cornea, limbal sclera, iris, and ciliary body from a control donor were similar, although several polypeptide bands were unique to each structure. PMID- 8197912 TI - [The effects of long-term topically applied prostaglandins on aqueous protein concentration and the rabbit ciliary process]. AB - I examined the effects of topically applied prostaglandin (PG) and novel PG related compounds on the blood-aqueous barrier (BAB) in the rabbit eyes. Latanoprost (PhXA41), PGF2 alpha-isopropyl ester (PGF2 alpha-IE) or PGE2 were topically applied once only or once daily for 8 weeks. Aqueous flare was measured with a laser flare cell meter. After the repeated application for 8 weeks, the morphological changes of the ciliary portion of ciliary processes were investigated with horseradish peroxidase (HRP) as a protein tracer. PGF2 alpha-IE 1.5 microgram, 3.0 micrograms, PGE2 1.5 microgram caused an initial rise of aqueous flare, but PhXA41 1.5 microgram caused no aqueous flare rise. After the application of PhXA41 1.5 microgram or PGF2 alpha-IE 1.5 microgram for 8 weeks, no morphological changes in the ciliary portion of ciliary process were found. After PGF2 alpha-IE 3.0 micrograms or PGE2 1.5 microgram for 8 weeks, HRP passed through the tight junction of non-pigmented epithelial cells and there was dilatation of rough-surfaced endoplasmic reticulum in the non-pigmented epithelial cells. PMID- 8197913 TI - [Detection of herpesvirus DNA in intraocular tissues]. AB - To elucidate the pathogenic mechanism of end-ophthalmitis due to viruses of the herpes family, one approach is to utilize the polymerase chain reaction (PCR) method for detection of the viral DNA. Using PCR, we examined 15 human eyes for the presence and distribution of DNA of the herpes simplex virus (HSV), varicella zoster virus (VZV), Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), and human herpesvirus-6 (HHV-6). HSV DNA was found in the retinal pigment epithelium (RPE) of 3 eyes, VZV DNA was found in the RPE of 2 eyes and the retina of 1 eye, EBV DNA was found in the iris and ciliary body of 2 eyes, the retina of 4 eyes, the RPE of 2 eyes, and the choroid of 1 eye, and HCMV DNA was found in the retina and choroid of 1 eye. These results indicate the possibility that herpes family viruses have an affinity for intraocular tissues, particularly the retina and the RPE. PMID- 8197914 TI - [Alteration of gamma-aminobutyric acid in streptozotocin-induced diabetic rat retina]. AB - To elucidate possible alteration of gamma-aminobutyric acid (GABA) in the diabetic retina, the distribution and determination of GABA was analyzed in streptozotocin-induced diabetic and normal rats after electroretinogram (ERG) recording. Immunoreactivity of GABA was found in the inner nuclear layer, inner plexiform layer, and ganglion cell layer in normal and diabetic rats. In the inner nuclear layer, strong immunoreactivity of GABA was found in amacrine-like cells. In diabetic retinas, GABA immunoreactivity was higher than in normal retinas. The contents of GABA increased began 1 week after occurrence of diabetes mellitus, attained a maximum at 2 months, and maintained this amount for 5 months. The latencies of oscillatory potentials of ERG were prolonged beginning 1 month after occurrence. These results suggest that increase of GABA in the amacrine cells of diabetic retinas may be related with the abnormality of oscillatory potentials. PMID- 8197915 TI - [Reaction of the retina to injected subretinal fluids]. AB - Experimental retinal detachment was produced by injecting various fluids into the subretinal space in pigmented rabbits. We selected autologous aqueous humor, autologous vitreous, and autoserum as substitutes for subretinal fluid. Retinal detachment disappeared within 24 hours. The eyes were enucleated 7 days after surgery for histopathological study. Destructive changes in photoreceptor layer occurred most severely when the eye was treated with serum. There was a decrease in the number of outer nuclear layer cells. Macrophages and fibroblastic cells had migrated into the subretinal space. Histopathological changes with vitreous were less pronounced than with serum. The cytoplasm of Mueller cells appeared to compensate for the loss of photoreceptor cells in the outer nuclear layer. Mild decrease in the number of photoreceptor cells was the sole pathological feature when the eye was treated with aqueous humor. The retina thus showed different reactions to the subretinal fluids of differing nature. PMID- 8197916 TI - [Immunohistochemical localization of blood-retinal barrier breakdown after argon laser photocoagulation in the monkey retina]. AB - Retinal photocoagulation induces breakdown of the blood-retinal barrier (BRB), but the site of the breakdown is not precisely known. The breakdown and repair of BRB following argon laser photocoagulation were studied in the monkey retina by immunohistochemical localization of serum albumin. Argon laser photocoagulation was performed to obtain ordinary burns as in human use. 1, 3, and 7 days after photocoagulation, serum albumin was observed in the outer retina and retinal pigment epithelium, but not around the retinal blood vessels. The immunostaining disappeared within 14 and 28 days after photocoagulation. The results of this study suggest that photocoagulation induces local breakdown of the outer BRB and that the breakdown is repaired within 14 days. PMID- 8197917 TI - [Proteoglycan in Bruch's membrane of senescence accelerated mouse: localization and age-related changes]. AB - We demonstrated the distribution of sulfated proteoglycans in Bruch's membrane of Senescence Accelerated Mouse histochemically and ultrastructurally using cuprolinic blue in conjunction with specific enzyme treatments and nitrous acid digestion. Two kinds of proteoglycan filaments were observed in the inner and outer collagenous layers, i.e., small collagen fibril-associated filaments (11 nm in average length), and large filaments (32 nm in average length). Intermediate size filaments (25 nm in average length) were seen in the basement membranes of the retinal pigment epithelium and choriocapillaris. Chondroitinase AC treatment eliminated the staining of filaments in the collagenous layers (chondroitin sulfate). Chondroitinase ABC treatment also eliminated the staining of filaments in the collagenous layers (chondroitin sulfate and dermatan sulfate). Nitrous acid eliminated the staining of filaments in both basement membranes (heparan sulfate). Proteoglycans containing chondroitin sulfate and dermatan sulfate were associated uniquely with collagen fibrils. Heparan sulfate proteoglycans were associated with the basement membranes of the pigment epithelium and choriocapillaris. With aging, the thickness of the basement membrane of the choriocapillaris and the staining of the filaments in the basement membranes of the pigment epithelium and choriocapillaris (heparan sulfate proteoglycans) increased. Collagen fibers became disarranged and the staining of both filaments in the collagenous layers decreased. The results of the staining characteristics probably reflect the aging of Bruch's membrane. PMID- 8197918 TI - [Acanthamoeba isolation from contact lens solution of contact lens wearers without keratitis]. AB - Acanthamoeba keratitis seems to be associated with wearing contact lenses. As controls, we surveyed contact lens wearers without keratitis. Contact lens solutions of 93 persons were examined in order to identify risk factors for contamination by Acanthamoeba. Therefore, the contact lens disinfection system and storage schedules were studied in each case. Acanthamoeba organisms were isolated from 4 specimens (4.3%). The incidence of Acanthamoeba was higher in specimens of soft contact lens solution than in those of hard contact lens solution, and all the Acanthamoeba positive cases had been using tap water. PMID- 8197919 TI - [The lipoproteins in human diabetic cataract]. AB - Four kinds of lipoproteins contained in human diabetic cataract lens were separated by of sequential flotation in an ultracentrifuge, and the quantities of each were determined by selective precipitation. Chylomicron, very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) were separated from cataract lenses as lipoprotein fractions, and quantified. Chylomicron was present in the largest quantity among the four. There was no significant difference between the total amount of lipoprotein contained in diabetic cataract lenses (96.95 +/- 4.03 micrograms/lens) and that in senile cataract lenses (89.51 +/- 8.35 micrograms/lens). The quantities of VLDL and LDL, however, were significantly larger in diabetic cataract lenses (14.84 +/- 0.55 and 20.97 +/- 0.58 micrograms/lens, respectively) than in senile cataract lenses (6.30 +/- 0.46 and 7.45 +/- 0.61 micrograms/lens, respectively). We demonstrated histologically that LDL receptors are localized on the lens epithelium and its underlying layer. PMID- 8197920 TI - [Lectin electron histochemistry in the skin in patients with exfoliation syndrome]. AB - Exfoliation syndrome has recently been suggested to have a more widespread distribution from the findings of exfoliative-like material outside the globe. To determine whether exfoliative-like material and exfoliative material are identical, they were characterized by electron microscopic lectin histochemistry using sixteen kinds of lectin; PNA, RCA60 and 120, ABA, DBA, SBA, ConA, LCA, WGA, DSA, PHA-E4 and L4, UEA-I, Lotus, MAM and SSA. The staining pattern indicated that sugar residues in these two materials on the trabecular meshwork, lens, and skin have the same characteristics, containing glycoconjugates with sugar residues of beta-galactosyl, alpha-mannosyl, N-acetyl-D-glucosaminyl, and terminal sialic acid. PMID- 8197921 TI - [Incidence of cataract and retinal detachment associated with atopic dermatitis]. AB - The incidence of cataract and retinal detachment associated with atopic dermatitis is reported. The subjects suffered from moderate or severe atopic dermatitis. Seventy-five patients (32 male and 43 female, age: 7-46, mean 19.7 years) had their initial examination at the Department of Ophthalmology, Sapporo Medical University Hospital, from 1981 to 1990. Cataract was found in 13 (6 male and 7 female) out of the 75 patients (17.3%). All cases except one already had cataract at the initial visit. The average age was 21.2 years. Nine had bilateral cataracts and four had unilateral. Type of cataract in 22 eyes was anterior subcapsular cataract (n = 3), posterior subcapsular cataract (n = 8), anterior and posterior cataract (n = 9), and mature cataract (n = 2). Retinal detachment was associated in six (8.0%) out of the 75 patients. Four were male and two were female. The average age was 21.6 years (range 18-29). Three cases were bilateral and 3 unilateral. Five of nine eyes with retinal detachment had no history of intraocular surgery. Four of the nine had a history of cataract extraction (3 eyes) and trabeculectomy (1 eye). Tears were observed in 5 out of 9 eyes (small tears in the peripheral retina (n = 1), oral dialysis (n = 3), and breaks at the pars plicata (n = 1). Tears could not be observed in four eyes (44%). Detachment of the pars plana was found in seven eyes. Retinal detachment was always associated with cataract. PMID- 8197922 TI - [Effect of intraocular irrigating solution on flicker electroretinogram during cataract surgery in humans]. AB - We studied the effects of intraocular irrigating solutions on the 30Hz flicker electroretinogram (ERG) during extracapsular cataract surgery in 45 eyes of 35 patients. The effects of two commercially available irrigating solutions. S-MA2 (Opeguard MA) and DE-057 (BSS Plus) were compared. After irrigation and aspiration (I/A) of the residual cortex with S-MA2, ERG amplitude increased to 111.2 +/- 5.8% of the pre-I/A amplitude. It significantly increased to 116.9 +/- 7.0% at the end of operation (p < 0.05) compared with before I/A. After I/A with DE-057, ERG amplitude increased to 109.5 +/- 5.3% of the pre-I/A amplitude. It significantly increased to 115.7 +/- 6.5% at the end of operation (p < 0.05) compared with before I/A. After I/A with S-MA2, ERG peak time was significantly prolonged to 103.9 +/- 0.8% of the pre-I/A peak time (p < 0.01). It was significantly shortened to 101.5 +/- 0.9% at the end of the operation (p < 0.001) compared with after I/A. After with DE-057, ERG peak time was significantly prolonged to 104.2 +/- 1.2% of the pre-I/A peak time (p < 0.01). It was significantly shortened to 101.3 +/- 1.22% at the end of the operation (p < 0.05). There were no statistical differences between changes of amplitude and peak time with S-MA2 and those with DE-057. We speculated that a drop in the retinal temperature during I/A in the anterior chamber and an increment of the photopic ERG amplitude during light adaptation with the operating microscope caused these ERG changes. PMID- 8197924 TI - Intravesical mitomycin C for the treatment of carcinoma in situ of the bladder: 36 months follow-up. AB - Mitomycin C (MMC) was given intravesically over a period of 36 months to 14 patients with transitional-cell carcinoma in situ of the bladder (CIS). Initial complete response was obtained in 10 patients. Of these patients, 5 presented recurrences; one in T2 at the 32nd month, one had a relapse of CIS with diffusion to the prostatic urethra at the 34th month: both patients underwent cystectomy. The remaining three patients presented Ta or T1 relapses and underwent endoscopic resection and a new instillation of MMC. The 4 patients who did not respond were treated with a new instillation of MMC:3 were unsuccessful and underwent cystectomy (one at the 9th month, one at the 12th month for progression to T2 and one at the 14th month for involvement of the prostatic urethra); the 4th patient responded to the treatment but at the 14th month had a relapse of CIS and he underwent cobalt-therapy. At the 36th month, 7 out of 13 patients were free from neoplasm. A neoplastic progression occurred in 3 patients: one out of the 9 patients who responded to the treatment and two out of the 4 who did not respond. Diffusion to the prostatic urethra was observed in 2 of the 13 patients; one patient responded to MMC and the other did not. Five patients underwent cystectomy: 3 for neoplastic progression and 2 for involvement of the prostatic urethra. MMC seems to be effective for the treatment of CIS of the urinary bladder and the absence of a response to chemotherapy must be considered an adverse prognostic factor for the neoplastic progression. PMID- 8197925 TI - Basic research in prostate cancer: molecular biology. AB - While a general appreciation for the importance of chromosomes in the development of cancer has existed for decades, molecular genetic analyses have gained considerable attention in recent years through identification of proto-oncogenes and tumor suppressor genes. Several different chromosomal aberrations, alterations of proto-oncogenes and suppressor genes have been described in prostate cancer. Loss of genetic material has been found to occur most frequently on chromosomes 7, 8, 10 and 16. The existence of tumor suppressor genes relevant to prostate carcinogenesis is suspected in these chromosomal locations. Several investigators are currently trying to identify these genes. Altered expression of several different oncogenes has been reported in prostate cancer. Among these, the ras- and myc-families of oncogenes have been studied most intensively. Structural oncogene alterations have been detected infrequently, most of the changes appear to occur transcriptionally. Despite an abundance of clinical material, knowledge about genetic lesions in prostate cancer is still very limited and sometimes conflicting results have been reported. With recent methodologic improvements and a growing interest in correlating genetic alterations with clinical disease progression, definition of prostate carcinogenesis at the molecular level will advance rapidly in the near future. PMID- 8197926 TI - Design and analysis of prostate cancer trials. AB - This paper presents an overview of various statistical concepts related to the design and analysis of prostate cancer trials: the need for randomization, stratification for prognostic factors, sample size determination, trial objectives, the choice of a control group, patient entry criteria, the number of treatments to be compared, the choice of endpoints, analysis by the intent to treat principle, interim statistical analysis and early stopping rule, and subgroup analyses. PMID- 8197927 TI - Quality control in data monitoring of clinical trials. AB - Eligibility of a patient is based on the patient's status at the time of registration/randomization in the trial and not on something that happens to the patient after entry in the study. All patients entered must be included in the statistical analyses and accounted for in the publication of the results. Stratification done at the time of randomization is used to avoid major imbalances with respect to the distribution of prognostic factors in the different treatment groups. This goal is accomplished only if the information given at randomization is accurate. For this reason, all information given at randomization should be recorded and inserted in the patient's medical file and the randomization done as close as possible to the start of treatment. Protocol violations are to be anticipated but must be kept as low as possible because their percentage will reflect on the quality of the trial. Patients lost to follow up must be kept to a minimum. If patients can no longer attend the consultations at the frequency described in the protocol, every attempt should still be made to follow them for survival. Finally, a clinical trial should be conducted in the time interval foreseen to maintain interest and patient recruitment. PMID- 8197928 TI - Flow cytometry in prostate cancer: histological and clinical correlation. AB - DNA histograms were obtained by flow cytometry for 39 human prostate carcinomas (27 total prostatectomy specimens, 5 biopsies and 7 transuretral resections). The study was performed on formalin-fixed and paraffin-embedded material. In this report, ploidy index did not seem to be a good marker of prognosis as no significant variation in ploidy was found neither among the different stages nor among the different Gleason categories. Proliferative index of the tumors seemed to be a more sensitive parameter; a significant relation was observed between proliferative index and stage of the tumor. The authors discuss these results under the light of previously reported observations. PMID- 8197929 TI - Laparoscopic pelvic lymphadenectomy. AB - We analyzed our first 41 patients with localized prostate cancer treated with laparoscopic pelvic lymph node dissection (LPLND) as staging procedure followed either by radical perineal prostatectomy or interstitial radiotherapy. 7/41 patients (17%) had pelvic lymph node metastases and received endocrine therapy. Overall complication rate was low (7.5%) and no major complication occurred. LPLND is minimally invasive and provides staging accuracy in prostate cancer. PMID- 8197930 TI - The experience of radical prostatectomy for locally confined prostate cancer in Liege. AB - The authors report their experience of 148 radical prostatectomies performed for adeno-carcinoma. They expose the reasons which have led them to adopt this kind of treatment and the reasons explaining a nearly exponential increase of the frequency of the operation during the last 5 years. They underline the importance of lymphadenectomy and the safety of frozen sections of the nodes. The surgical technique is briefly commented and the (low) morbidity of the operation is reviewed. They compare the results of RPV to those of external radiotherapy, watchful attitude or immediate hormonal treatment and they conclude in insisting on the benefit of the surgical approach as far as indications (which are defined) are strictly followed. PMID- 8197931 TI - [Hormone therapy before radical prostatectomy. Effects on surgical method and resection margins. Belgian Uro-Oncological Study Group (B.U.O.S.)]. AB - 127 patients with a clinical stage T2b and T3 prostate cancer were randomized in order to undergo either a radical prostatectomy alone or a radical prostatectomy after hormonal treatment (560 mg of estramustine phosphate daily for 6 weeks) in a prospective multi-center study. The clinical or radiological evaluation of an eventual downstaging being extremely difficult, the authors compared in the 2 groups the influence on the surgical act and the number of positive surgical margins at pathological examination of the resected specimen. There was no significant difference between the 2 groups concerning the surgery (duration of the procedure, blood transfusion, degree of difficulty). For clinical T2 prostate tumors the number of positive surgical margins was significantly lower in the group that had preoperative hormonal treatment. In the group with clinical T3 prostate cancer this difference was not found. The influence of positive margins on the later development of local or systemic recurrence and on survival still has to be awaited. At this moment one could conclude that only patients with a T2 prostate cancer benefit of a preoperative hormonal treatment. PMID- 8197932 TI - Total androgen blockade in the treatment of hormone-resistant metastasized prostate carcinoma. A literature review. AB - Once hormone resistance has been developed in metastasized prostate cancer, the main aim of therapy is to ensure quality of life. Total androgen blockade which neutralizes the androgens of adrenal origin provides a therapeutic modality which gives +/- 16% objective and +/- 50% subjective response during several months. The two drugs actual available in Belgium are flutamide and cyproterone acetate. Especially flutamide has been used for this purpose. As the number and intensity of side effects is low, this can be considered as a first choice treatment when prostate cancer escapes its first line therapy. PMID- 8197933 TI - Androcur 50 in the treatment of prostatic carcinoma. Belgian multicentric study with the participation of 30 urologists. AB - Androcur 50 was administered as monotherapy (n = 73) or as combined therapy with LH-RH agonists (n = 130) in 203 patients during a 6 month period. Eighty two patients had a local invasive disease, 119 had metastatic disease and 2 had a tumor confined to the prostate. Quality of life could be evaluated in 164 patients considered as valid cases for efficacy analysis. General well being improved in 41% of the patients, appetite was better in 34% of the patients and weight increased in 36%. Pain due to metastatic disease decreased or stabilised in 96% of the patients. Of the 203 patients, 8 patients had objective metastatic progression which led to death in one patient. The incidence of side effects observed in all 203 is as follows: 9% gynaecomastia, 6.5% gastro-intestinal disorders. Hot flushes were reported in 2% of the patients in the monotherapy and in 13% of the patients in the combined treatment. This open not controlled trial shows that the use of Androcur 50 in monotherapy or in combined treatment is an effective drug for prostatic carcinoma, improves quality of life and is generally well tolerated. PMID- 8197934 TI - Fast spin-echo MR in the detection of vertebral metastases: comparison of three sequences. AB - PURPOSE: To examine the relative capabilities for the detection of vertebral metastases of three available fast spin-echo sequences: T1-weighted fast spin echo, short tau inversion recovery (STIR) fast spin-echo, and T2-weighted fast spin-echo sequences with chemical shift selective saturation pulse fat suppression. METHODS: Fourteen patients were evaluated prospectively over a 2 month period with T1-weighted fast spin-echo (four echo train, four acquisitions, 1 min 59 sec-2 min 37 sec). STIR fast spin-echo (16 echo train, four acquisitions, 2 min 30 sec-3 min 19 sec), and T2-weighted fast spin-echo (16 echo train, 4 acquisitions, 2 min 27 sec-3 min 16 sec). For all three pulse sequences, measurements were obtained of the signal intensities of normal marrow, abnormal marrow, fat, and noise posterior to the spine. Contrast-to-noise ratios were calculated for metastases in each case. Lesions were evaluated by three observers and rated for size, location, and conspicuity. RESULTS: Signal intensities of fat, normal marrow, and noise were highest for T1-weighted fast spin-echo sequences. STIR fast spin-echo and fat-suppressed T2-weighted fast spin-echo had approximately similar fat-suppression capabilities. Though contrast-to-noise ratios were highest overall for STIR fast spin-echo, the finding was not statistically significant and lesion conspicuity was deemed better with fat suppressed T2-weighted fast spin-echo and T1-weighted fast spin-echo images. Discrete lesions were well identified on all three pulse sequences. CONCLUSION: Fast spin-echo sequences appear promising for the detection of vertebral metastases. Further work should be directed toward comparison with conventional spin-echo to determine whether fast spin-echo may replace conventional spin-echo sequences for evaluation of vertebral metastases. PMID- 8197935 TI - Evaluation of fat suppression in contrast-enhanced MR of neoplastic and inflammatory spine disease. AB - PURPOSE: To determine the benefit of fat suppression in conjunction with gadolinium enhancement for evaluating neoplastic and inflammatory diseases of the spine. METHODS: Contrast-enhanced T1-weighted images were compared with the corresponding contrast-enhanced T1-weighted images with fat suppression in 14 patients with various neoplastic and inflammatory spine diseases. RESULTS: Contrast-enhanced T1-weighted images with fat suppression showed enhancing lesions in all cases of vertebral disease (five cases), but in one case some metastases did not enhance. Paravertebral (nine lesions), epidural (seven lesions), and intradural-extramedullary (six lesions) were delineated better with contrast-enhanced fat suppression. In the 14 cases (29 lesions), nine lesions were seen only on contrast-enhanced images with fat suppression. Integrity of the vertebral end plates was assessed more accurately on fat-suppressed images. CONCLUSION: Although noncontrast T1-weighted images are sufficient to screen for vertebral disease, contrast-enhanced images with fat suppression may detect additional lesions. Fat suppression should be used in conjunction with gadolinium for evaluating epidural, paravertebral, and intradural-extramedullary spinal lesions. PMID- 8197936 TI - Contrast enhancement of normal intervertebral disks: time and dose dependence. AB - PURPOSE: To determine the dose of contrast medium and the imaging strategy sufficient to detect diffusion of low-molecular-weight gadolinium-containing contrast media into normal intervertebral disks. METHODS: In 11 rabbits, sequential MR images were obtained of the spine for 120 minutes after intravenous injection of gadopentetate dimeglumine in doses of 0.1 to 2.8 mmol/kg. Images were inspected for evidence of contrast enhancement. Signal intensity was measured and plotted as a function of time and dose. RESULTS: Contrast enhancement was detected by inspection of images and by measurement in animals receiving doses of 0.3 mmol/kg and larger. CONCLUSIONS: Diffusion of gadolinium containing chelates into the intervertebral disk can be detected with clinically used doses of commercially available contrast medium. Therefore, with MR and a gadolinium-containing contrast medium, diffusion into intervertebral disks can be studied. PMID- 8197937 TI - MR assessment of brain maturation: comparison of sequences. AB - PURPOSE: To evaluate the role of short-inversion-time inversion-recovery (STIR) sequences in assessment of brain maturation. METHODS: Twenty-seven infants and young children with normal neurologic development were examined by 1.5-T MR using a circularly polarized head coil. Axial T1-weighted and T2-weighted and spin-echo and STIR images were obtained. Signal intensity of different anatomic structures at individual sequences was classified relatively to reference sites and temporal sequence of signal intensity was observed. RESULTS: Signal intensity changes on T1-weighted and T2-weighted spin-echo sequences occurred at ages described in various previous publications. On STIR images intensity changes became apparent at a time between T1-weighted and T2-weighted images. The advantages of the STIR sequence were improved assessment of myelination of subcortical cerebral white matter from 6 to 14 months and good contrast between white matter lesions and cerebrospinal fluid. CONCLUSION: Our results suggest that from 0 to 6 months myelination can be assessed best using a combination of T1-weighted and T2 weighted images; from 6 to 14 months a combination of T2-weighted and STIR images seems to be advantageous; after 14 months the use of only T2-weighted sequences is sufficient. After 14 months STIR images may be useful in detecting small periventricular white matter lesions or in cases with retarded myelination and isointensity between gray matter and white matter. PMID- 8197938 TI - MR of pediatric intracranial meningiomas. AB - PURPOSE: To assess MR and pathologic characteristics of childhood intracranial meningiomas, comparing the radiographic findings with those observed in adult intracranial meningiomas. METHODS: Clinical records, MR and CT scans, and histology of eight children with intracranial meningiomas presenting for a period of 7.5 years were retrospectively reviewed. RESULTS: Boys equaled girls but predominated from ages 4 to 11 years. The ages ranged from 4 to 18 years. Two patients had radiation-induced meningiomas. Two children had multiple lesions; neither had neurofibromatosis. All solitary lesions were supratentorial. Other characteristics included: dural-based attachment (n = 6); large size (> 5 cm) (n = 4); cystic components (n = 3); and intraventricular location (n = 1). Histologic subtypes were: meningothelial (n = 4); transitional (n = 3); and fibroblastic (n = 1). Preoperative diagnoses of meningiomas were made in six cases based on overall imaging characteristics. CONCLUSIONS: Diagnosis of childhood intracranial meningiomas does not differ from that of adults radiographically, with the exception of larger tumor sizes. PMID- 8197939 TI - A method for sonographic counting of the lower vertebral bodies in newborns and infants. AB - PURPOSE: To determine whether the lumbosacral junction of the vertebral column can be identified with sonography in newborns and infants and thus serve as a method for counting the lumbar and sacral vertebral bodies. METHODS: In 32 newborns and infants, the number of ossified vertebral bodies distal to the lumbosacral junction was counted with sonography and radiography. RESULTS: Sonographic and radiographic findings agreed in 29 of 32 examinations (91%). CONCLUSIONS: The lordotic transition at the lumbosacral junction can be identified with sonography in the majority of newborns and infants, allowing intraspinal structures to be related to a specific vertebral level. PMID- 8197940 TI - Clinical and MR correlates in children with extrapyramidal cerebral palsy. AB - PURPOSE: To identify the characteristic MR findings in extrapyramidal cerebral palsy. METHOD: Six patients who had suffered intrapartum asphyxia and who subsequently developed extrapyramidal cerebral palsy were identified. Asphyxia was evidenced by severe neonatal systemic acidosis as documented by a venous cord pH of less than 7.0 whenever available, or acidosis in subsequent arterial blood gas samples, and clinical signs of an acute hypoxic-ischemic encephalopathy during the neonatal period. In addition, 1- and 5-minute Apgar scores were 3 or less, and there had been need for intubation or vigorous resuscitation in the delivery room. There were three boys and three girls, all born at term, with birth weight appropriate for gestational age, and without a history of bilirubin levels above 15 mg/dL. MR imaging at 1.5 T was performed between 1 and 19 years of age. RESULTS: In all subjects focal high signal abnormality was demonstrated in the posterior putamen and the anterior or posterior thalamus. There were no other findings in most cases. CONCLUSION: MR demonstrated lesions in the putamen and thalamus in all of our six patients with severe extrapyramidal cerebral palsy who had suffered intrapartum asphyxia. PMID- 8197941 TI - MR of fetal central nervous system abnormalities. AB - PURPOSE: To investigate whether MR can provide additional information on fetuses with central nervous system abnormalities as demonstrated by ultrasonography. METHODS: Fetal MR examinations were studied prospectively in 22 pregnant women whose fetuses showed evidence of anomalies on ultrasound performed in the High Risk Obstetric Clinic. RESULTS: In 19 of 22 cases, postpartum confirmatory diagnoses were obtained by MR or CT examinations, autopsy, or surgery. In general, the image quality of MR is comparable with that of ultrasound. However, in six of 22 cases (27%), MR provided additional information that altered the ultrasound diagnosis; these included cases of infarction, diastematomyelia, normal hemimegalencephaly with early myelination, Dandy-Walker variant, and lipoma. All of these cases had postpartum confirmation. The additional information changed the treatment in three of six patients (no intervention or elective abortion). CONCLUSIONS: In certain situations MR can add valuable information to that obtained by sonography in the evaluation of the fetal central nervous system. PMID- 8197942 TI - Optimization of gradient-echo MR for calcium detection. AB - PURPOSE: To determine optimal MR gradient-echo sequences for the visualization of calcium in neurologic MR. METHOD: The dependence of signal intensity and image contrast on the imaging parameters repetition time, echo time, flip angle, and spoiling were measured for hydroxyapatite samples. Calculations of signal intensity were shown to correspond to these measures. RESULTS: Optimum detectability was obtained with an echo time of 29 msec and was independent of spoiling. As repetition time ranged from 30 msec to 700 msec, the optimal flip angle ranged from 17 degrees to 66 degrees. CONCLUSIONS: Gradient-echo sequences that optimize the contrast for detection of calcium in neurologic imaging have been determined. PMID- 8197943 TI - Preliminary experience with selective laser sintering models of the human temporal bone. AB - PURPOSE: To assess the accuracy of three-dimensional models of the human temporal bone generated from CT data. METHODS: Thin-section CT of a left human cadaveric temporal bone was performed using multiple-scan planes (axial, coronal, and sagittal) at 1.5-mm section thickness and 0.25-mm pixel size with an edge enhancement two-dimensional algorithm. CT data were converted to toggle point format based upon a threshold value of 200 (approximately -830 HU) obtained from prior experimentation with a CT phantom. Selective laser sintering of polycarbonate powder was performed at a beam diameter of 0.060 inches (1.5 mm), 100 scan lines per inch, layer thickness of 0.010 inches (0.25 mm), and layer repeat factor of 4. The polycarbonate models were then scanned in the axial, coronal, and sagittal planes and compared with the original CT data. Anatomic dissection of the models was performed for further verification of the imaging findings. RESULTS: Models of high anatomic accuracy were generated. Shortening by a factor of 0.67 along the Z axis secondary to the layer repeat factor of 4 resulted in distortion of the models. Distortion in the XY plane ranged from 0% to 20%. Differences in model accuracy based on the initial CT scan plane were observed. A significant amount of nonsintered or partially sintered polycarbonate resulted in intermediate density on the CT images. CONCLUSIONS: Selective laser sintering can result in accurate modeling of detailed anatomic structures in the human temporal bone. Further investigation of materials and factors contributing to the accuracy of selective laser sintering in the manufacturing of high resolution anatomic models is warranted. PMID- 8197944 TI - Idiopathic, herpetic, and HIV-associated facial nerve palsies: abnormal MR enhancement patterns. AB - PURPOSE: To determine specific criteria that can be used to define normal versus abnormal MR contrast enhancement of the facial nerve. METHODS: Twenty-three patients with acute unilateral inflammatory peripheral facial nerve palsy were examined on a 1.5-T MR using multiplanar T1-weighted spin-echo sequences before and after injection of gadopentetate dimeglumine. These MR patterns were compared with those of healthy control subjects. RESULTS: The normal facial nerve usually showed a mild to moderate enhancement of the geniculate ganglion and the tympanic mastoid segment. The intracanalicular-labyrinthine segment did not enhance. All patients showed abnormal enhancement of the distal intracanalicular and the labyrinthine segment. An intense enhancement could be observed in the geniculate ganglion and the proximal tympanic segment, especially in herpetic palsy. Associated enhancement of the vestibulocochlear nerve was seen in herpetic and idiopathic palsy. Enhancement of the inner ear structures was detected only in herpetic palsy. CONCLUSIONS: Abnormal contrast enhancement of the distal intracanalicular and the labyrinthine facial nerve segment is observed in all patients and is the only diagnostically reliable MR feature proving an inflammatory facial nerve lesion. The intense enhancement of the geniculate ganglion and the proximal tympanic segment is possibly correlated with the reactivation of the latent infection in the sensory ganglion. The abnormal enhancement results from breakdown of the blood-peripheral nerve barrier and/or from venous congestion in the venous plexuses of the epi- and perineurium. PMID- 8197945 TI - CT after intracranial intraarterial thrombolysis for acute stroke. AB - PURPOSE: To determine the incidence, appearance, and clinical significance of lesions mimicking intraparenchymal hemorrhages on CT in patients treated with intracranial intraarterial thrombolysis for acute strokes. METHODS: Ten cases of acute stroke treated with direct intraarterial urokinase infusion were retrospectively reviewed. Clinical and radiographic findings before and after therapy were all evaluated. RESULTS: Six (60%) of the 10 patients showed areas of increased attenuation on CT shortly after thrombolytic therapy. The lesions were associated with clinical deterioration in two cases (20%); in these two cases the lesions persisted on CT for several days. The lesions were asymptomatic in two (20%) cases; the lesions cleared on CT within 24 hours in those two patients. In two (20%) patients, immediate clinical improvement was evident despite the radiodense areas. These lesions also cleared within 24 hours. CT Hounsfield unit measurements of four of the lesions revealed very high Hounsfield units in two lesions, only one of which was a symptomatic lesion. MR in two cases revealed residue of hemorrhage. CONCLUSION: Intraparenchymal areas of increased attenuation may be seen on the CT scans of patients after intraarterial thrombolysis. The density is often at least partially attributable to contrast extravasation. The lesions should not necessarily be interpreted as hemorrhage alone, especially in the absence of clinical deterioration. Rapid clearing may be a positive prognostic sign. PMID- 8197946 TI - Self-expanding and balloon-expandable stents in the treatment of carotid aneurysms: an experimental study in a canine model. AB - PURPOSE: To assess the efficacy of metal stents for the treatment of different forms and sizes of carotid aneurysms. METHODS: A total of 14 experimentally constructed aneurysms in dogs were treated with transfemorally placed balloon expandable tantalum and self-expanding nitinol stents. RESULTS: In 10 cases, stenting produced either immediate complete occlusion of the aneurysm (n = 7) or complete delayed thrombosis after 7 to 10 days (n = 3). In two cases treated with balloon-expandable tantalum endoprostheses, repeated angiography showed a persistent aneurysmal neck with a diameter of 1 mm. No incompletely occluded aneurysms were visible after implantation of nitinol stents. Nine-month angiographic follow-up revealed maximal stenosis of the stented vessel segment of up to 40% after placement of tantalum endoprostheses. However, no more than 15% stenosis followed the deployment of nitinol stents. Histologic examination confirmed these findings. Significantly greater intimal fibrocellular tissue growth surrounded tantalum filaments than nitinol filaments, which were covered with a smooth, thin neointimal layer. In two carotid arteries a subtotal and total occlusion of the parent vessel occurred after the insertion of a tantalum and nitinol stent, respectively. No recanalization of completely occluded aneurysms or delayed migration of a stent was observed. CONCLUSIONS: Porous, tubular self-expanding nitinol stents may become the treatment of choice for broad-based and fusiform aneurysms of the internal carotid artery. However, blood flow dynamics of the aneurysms must be studied carefully in order to select an appropriate mesh size for complete occlusion while preserving the parent vessel. Improvements in the introducing system, stent material, and stent shape are required for simple implantation and reduction of intimal hyperplasia. PMID- 8197947 TI - Technical feasibility and performance studies of a Doppler guide wire for potential neuroendovascular applications. AB - PURPOSE: To conduct technical feasibility and performance studies on a new Doppler-tipped, 0.014-inch micro-guide wire for potential neuroendovascular applications. METHODS: In vivo microcatheterizations of brachiocephalic arteries were performed in two swine using the 0.014-inch Doppler guide wire and a commonly used microcatheter. A standardized, bench-top method of evaluating basic mechanical properties of micro-guide wires was also used to compare the 0.014 inch Doppler guide wire with a commonly used micro-guide wire. RESULTS: The 0.014 inch Doppler guide wire had similar steerability, tractability, torque control, and distal tip flexibility to the commonly used micro-guide wire in the in vivo simulations. Frequent micro-guide wire exchanges were possible without loss of superselective positioning of the microcatheter. Bench-top testing showed the 0.014-inch Doppler guide wire to have comparable distal tip flexibility and stiffness to the commonly used micro-guide wire. CONCLUSION: The comparable subjective and objective mechanical properties of the 0.014-inch Doppler guide wire to that of a commonly used micro-guide wire further establishes the possibility of clinical implementation of the device. PMID- 8197948 TI - Use of a Doppler guide wire for intravascular blood flow measurements: a validation study for potential neurologic endovascular applications. AB - PURPOSE: To conduct a validation study of a Doppler guide wire for potential neuroendovascular applications. METHODS: A 12-MHz, 0.018-inch Doppler guide wire was evaluated in eight swine under various blood flow conditions using two types of in vivo cerebrovascular models (physiologic and arteriovenous shunting). Flow conditions were mechanically and pharmacologically altered. Doppler average peak velocity was compared with volumetric blood flow, and flow profile corrections were calculated and analyzed. Qualitative aspects of the Doppler guide wire spectra were also assessed. RESULTS: Plots of average peak velocity versus volumetric blood flow showed excellent linear relationships (r2 > 0.94), which were maintained at high flow conditions (average peak velocity, 99 to 236 cm/sec; volumetric blood flow, 392 to 889 mL/min). Values of flow profile correction varied from 0.43 to 0.94 and showed no consistent relationship to changes in volumetric blood flow. CONCLUSIONS: The excellent correlation between average peak velocity and volumetric blood flow over a wide range of blood flow conditions and the additional qualitative information of the Doppler guide wire spectra establish a foundation for clinical implementation. The unpredictable variations of flow profile corrections remain obstacles for calculating volumetric blood flow based on Doppler guide wire average peak velocity. PMID- 8197949 TI - A technique for core biopsies of head and neck masses. AB - A technique for performing core biopsies of indeterminate masses of the extracranial head and neck is described. Four patients with suspicious masses of the extracranial head and neck underwent coaxial core biopsies through an 18 gauge Hawkins-Akins blunt tip needle. Three of the four patients had diagnostically adequate samples. There were no neurologic or vascular complications. PMID- 8197950 TI - Use of a coil introducer to shape microcatheters. AB - We have found that an angled tip with a 40-degree angle and a distal length of 1 to 3 mm can be useful in subselecting intracranial vessels whose origins are otherwise difficult to catheterize. In addition, curves can be introduced by shaping the coil introducer as needed. These shapes can be safely formed using a coil introducer inserted in a retrograde fashion and fixed in boiling water. PMID- 8197951 TI - Life-threatening anaphylactoid reaction after intravenous gadoteridol administration in a patient who had previously received gadopentetate dimeglumine. AB - We report a case of a life-threatening anaphylactoid reaction to gadoteridol. The reaction resulted in hospitalization but did respond to medical treatment. Resuscitation equipment and properly trained personnel should be available if these agents are being administered. PMID- 8197953 TI - Giant Rathke cleft cyst. AB - The preoperative diagnosis for an unusual skull base lesion was chordoma. The combination of imaging, pathologic, and surgical findings suggests the diagnosis of Rathke cyst. PMID- 8197952 TI - Rathke cleft cysts: correlation of enhanced MR and surgical findings. AB - PURPOSE: To describe the gadolinium-enhanced MR findings of Rathke cleft cyst correlate them with the surgical findings, and define those preoperative findings that differentiate this lesion from other sellar and juxtasellar tumors. METHODS: We studied 18 patients who were diagnosed as having Rathke cleft cyst pathologically. These patients were imaged with T1- and T2-weighted coronal and sagittal spin-echo sequences. Fifteen of these patients received gadopentetate dimeglumine. RESULTS: In eight patients, the cyst showed low intensity on T1 weighted images and high intensity on T2-weighted images. At surgery, the cyst fluid was cerebrospinal fluid-like or light brown in five patients, motor oil like in one patient, and milky in two patients. In 10 patients, cysts showed isointensity to high intensity on T1-weighted images and had various intensity on T2-weighted images. All 10 contained milky fluid. In three patients the intensity of fluid was heterogeneous. A waxy nodule was found in two patients. The position of the normal pituitary gland confirmed by surgery in all cases coincided with enhancement on MR imaging. The variable position of the normal pituitary gland was clearly identified in the sagittal images. The cyst walls showed no enhancement by gadopentetate dimeglumine. CONCLUSIONS: Because Rathke cleft cysts show variable intensities on MR, the diagnosis is often difficult when based on MR signal intensity values alone. MR imaging with gadopentetate dimeglumine does assist in the diagnosis of Rathke cleft cysts. Diagnostic clues include the lack of cyst wall enhancement and displacement of the normal pituitary gland. PMID- 8197954 TI - Decreased pituitary gland height after radiation treatment to the hypothalamic pituitary axis evaluated by MR. AB - PURPOSE: To evaluate treatment-related changes in pituitary gland morphology after childhood cancer and to compare these findings with growth data. METHODS: Forty-three survivors of childhood cancer were evaluated by cranial MR imaging. Twenty-nine of the patients had received radiation therapy to the hypothalamic pituitary axis with doses of 10 to 46 Gy. The height of the pituitary gland was measured from midline sagittal images and compared with age- and sex-matched controls. Pituitary gland heights were compared with body height standard deviation scores in patients. RESULTS: The patients who had received radiation therapy to the hypothalamic-pituitary axis had significantly smaller pituitary glands than patients in the nonirradiated group or their age- and sex-matched controls (mean, 3.5 mm versus 5.9 and 5.8 mm, respectively). They were also significantly shorter than patients in the nonirradiated group. CONCLUSION: Radiation therapy to the hypothalamic-pituitary area may lead to poor growth of the pituitary gland and short stature. PMID- 8197955 TI - Digital angiotomosynthesis for preoperative evaluation of cerebral arteriovenous malformations and giant aneurysms. AB - PURPOSE: To evaluate the clinical utility of the digital angiotomosynthesis technique for giving additional information regarding critical anatomy of cerebrovascular lesions before surgical intervention. METHOD: Seven arteriovenous malformations and three giant aneurysms were examined with digital angiotomosynthesis; these images were compared with conventional angiograms. RESULTS: 1) Detailed recognition of three-dimensional vascular structures of the arteriovenous malformation and giant aneurysm was facilitated by the cine mode of digital angiograms and angiotomograms. 2) Reconstructed angiotomograms could show clear separation of overlapping vessels and demonstrate fine vasculature. 3) Fine feeders, which were difficult to trace on the conventional angiogram, were more easily recognized in all cases of arteriovenous malformation. 4) Small arteries passing in close proximity to the arteriovenous malformation nidus were identifiable. 5) Fine arterial branches, being obscured by big shadows of giant aneurysms on the conventional angiograms, were well identified. 6) The anatomic relationship of bone structures to the giant aneurysm was clearly shown. CONCLUSIONS: Digital angiotomosynthesis is helpful for recognizing the three dimensional and detailed vascular anatomy of arteriovenous malformations and giant aneurysms and provides neurosurgeons with useful information for preoperative evaluation. PMID- 8197956 TI - An orbital arteriovenous malformation in a patient with origin of the ophthalmic artery from the basilar artery. AB - An abnormal origin of the ophthalmic artery from the basilar artery, found in conjunction with an orbital arteriovenous malformation, is described. The successful treatment of the arteriovenous malformation by embolization through the ophthalmic artery is also reported. PMID- 8197957 TI - Hyperostosis in meningiomas: MR findings in patients with recurrent meningioma of the sphenoid wings. AB - PURPOSE: We used MR imaging to analyze retrospectively the pattern of hyperostosis occurring concomitantly with recurrent sphenoid wing meningiomas. METHODS: Bone involvement was compared in 12 corresponding CT and MR studies of 10 female patients with sphenoid wing meningiomas recurrence after earlier surgical treatment. Four of these had histologically confirmed meningiomatous infiltration of the bone. RESULTS: All patients had CT findings of localized hyperostosis of parts of the sphenoid wings. MR revealed inhomogeneous areas of slightly increased signal intensity in hyperostotic bone on T2-, proton density- and T1-weighted sequences. In nine of 10 patients, segments of the hyperostotic bone showed different degrees of gadolinium enhancement. CONCLUSIONS: Because earlier studies have revealed high incidences of meningiomatous bone infiltration in sphenoid wing meningiomas, and because infiltration was confirmed in four of our patients, we postulate that the gadolinium enhancement in the area of hyperostosis may be related to meningiomatous bone infiltration. PMID- 8197958 TI - Gas in the cavernous sinus. AB - PURPOSE: To evaluate the significance of cavernous sinus gas identified on head CT scans. METHODS: Head CT scans were viewed prospectively for a period of 3 years. The charts of patients who demonstrated cavernous sinus gas were reviewed. RESULTS: Seventeen patients without head trauma and 10 patients with head trauma demonstrated gas in the cavernous sinus. None of the patients had symptoms or developed symptoms originating in the cavernous sinus. All of the patients without trauma had an intravenous line in place. Sphenoid fractures or basilar skull fractures were not a constant finding in trauma patients with cavernous sinus gas. CONCLUSIONS: In patients without symptoms referable to the cavernous sinus, gas in the cavernous sinus does not appear to be a significant finding. The gas is most likely the result of venous air emboli from intravenous lines or penetrating trauma. PMID- 8197959 TI - Location of hand function in the sensorimotor cortex: MR and functional correlation. AB - PURPOSE: To determine the location of hand function in the sensorimotor cortex using MR and positron emission tomography imaging studies. METHODS: Anatomic and physiological methods were used for this study. Anatomic study was based on the MR analysis of 22 subjects. The length of the sensorimotor cortex was measured in the axial and sagittal planes. Physiologic study was based on the positron emission tomography studies of 4 subjects. Each of the studies was correlated with MR. RESULTS: We found that the superior genu of the central sulcus corresponds to hand function in the sensorimotor cortex. This level may prove useful for any clinical correlations or for surgery. CONCLUSIONS: From this study, the hand function area in the sensorimotor cortex is easily understood with its characteristic shape in axial MR scan. The comparison of MR and positron emission tomography data clearly show anatomic correlations. This may be applied to the functional mapping of the pathologic studies in the sensorimotor cortex regions. PMID- 8197960 TI - Histologic abnormalities associated with gadolinium enhancement on MR in the initial hours of experimental cerebral infarction. AB - PURPOSE: To determine the histologic changes associated with gadopentetate dimeglumine enhancement on MR images in acute focal cerebral ischemia. METHODS: In each of two baboons, a microcatheter was used to occlude partially the middle cerebral artery and reduce cerebral blood flow for approximately 3.5 hours. The catheter was then removed allowing reperfusion for approximately 3.5 hours. In two other baboons, cerebral blood flow was completely and irreversibly interrupted by injecting liquid adhesive into the middle cerebral artery. T2 weighted and serial enhanced T1-weighted MR images were obtained. Brain specimens were studied histopathologically. RESULTS: In the animals with incomplete and reversible reduction of cerebral blood flow, postcontrast T1-weighted images obtained during the initial 3 hours of ischemia showed focal areas of hypointensity. These areas were enhanced on later images. The areas of signal abnormality were subsequently found to be necrotic and were characterized by neuronal cytolysis and vascular "plugging." In the animals with complete and irreversible interruption of cerebral blood flow, no abnormal signal intensity or enhancement was observed. Histologic abnormalities were milder in these animals. CONCLUSIONS: Contrast enhancement on MR images in the initial hours of cerebral ischemia was associated with histologic evidence of tissue necrosis but was not associated with milder ischemic changes. PMID- 8197961 TI - Calcifying pseudotumor of the cervical spine. PMID- 8197962 TI - Osmotic blood-brain barrier disruption: CT and radionuclide imaging. AB - PURPOSE: To compare CT and radionuclide imaging of osmotic blood-brain barrier disruption. To develop a quantitative method for imaging osmotic blood-brain barrier disruption and to see if iopamidol could be safely given intravenously in conjunction with blood-brain barrier disruption. METHODS: Forty-five blood-brain barrier disruption procedures were imaged with CT and radionuclide scans. The scans were evaluated with visual and quantitative scales. Patients were observed for adverse effects after blood-brain barrier disruption. RESULTS: There was a 4% rate of seizures in this study. There was good agreement between visual CT and radionuclide grading systems. Quantitative methods to grade disruption did not add useful information to visual interpretations. CONCLUSIONS: Nonionic iodine based contrast medium has a lower incidence of seizures when injected intravenously in conjunction with osmotic blood-brain barrier disruption than ionic contrast material. Contrast-enhanced CT is the preferred method to image disruption because it has better spatial resolution than radionuclide techniques. PMID- 8197963 TI - Enhanced MR in the acute phase of Wernicke encephalopathy. AB - MR in a patient with Wernicke encephalopathy showed enhancement in the mamillary bodies and inferior quadrigeminal plate. These findings pointed to the correct diagnosis, which can be difficult to make in patients who are not alcoholics. PMID- 8197964 TI - Wernicke-Korsakoff syndrome caused by psychogenic food refusal: MR findings. AB - A 37-year-old woman developed Wernicke encephalopathy after prolonged psychogenic food refusal. MR revealed characteristic signal abnormalities in the midbrain and dorsal thalamus. Follow-up scans showed atrophy and third ventricular enlargement. Wernicke encephalopathy can occur in nonalcoholics, and MR imaging is useful in both the diagnosis and follow-up. PMID- 8197965 TI - Annotated bibliography. PMID- 8197966 TI - Free-radical activity after primary coronary angioplasty in acute myocardial infarction. AB - Free-radical activity in coronary venous outflow was assessed before and after reperfusion in nine patients with acute infarction who had undergone successful recanalization of the infarct-related artery by primary coronary angioplasty. Free-radical activity was measured in serum samples from coronary venous outflow over a timed period of 24 hours by using (1) the percentage molar ratio (PMR) of the diene conjugate 9,11-linoleic acid, and (2) malonaldehyde concentration. Preangioplasty PMR means lay within the normal range, but showed a marked increase soon after successful recanalization. Relative to baseline, the changes over time reached statistical significance between 2 and 60 minutes. No statistically significant changes in malonaldehyde occurred over the study period. We conclude that successful recanalization of the infarct artery is associated with significantly elevated free-radical activity, as measured by the PMR of conjugated diene, in coronary venous outflow. Such patients may be at risk from free radical mediated reperfusion injury. PMID- 8197967 TI - Plasma N-terminal atrial natriuretic peptide in acute myocardial infarction. AB - Plasma atrial natriuretic peptide (ANP) and the N-terminal (NT) fragment of the 126-amino acid prohormone of ANP (proANP; NT-proANP) were correlated with clinical findings in 41 patients with acute myocardial infarction and in 19 patients with angina pectoris. On admission to the hospital, the 39 patients with nonfatal infarction who subsequently had overt heart failure (n = 8) had plasma NT-proANP (2374 +/- 1038 pmol/L) and ANP (54 +/- 43 pmol/L) concentrations that were higher (p < 0.01) than those in the patients who remained without or who presented with minor signs of failure. In contrast to the relatively stable NT proANP levels, ANP decreased markedly during the first 24 hours in the patients who had any signs of failure. Hence the plasma levels of NT-proANP and ANP did not go hand in hand in acute myocardial infarction, and NT-proANP appeared to be a better marker of cardiac dysfunction than ANP. PMID- 8197968 TI - Transforming growth factor beta 1 preserves endothelial function after multiple brief coronary artery occlusions and reperfusion. AB - The objective of this investigation was to determine the effect of transforming growth factor beta 1 (TGF-beta 1) on endothelium-dependent relaxation in isolated epicardial coronary artery rings obtained from anesthetized dogs after multiple brief episodes of coronary artery occlusion and reperfusion in vivo. Dogs were subjected to four 5-minute periods of left anterior descending coronary artery occlusion interspersed with 5 minutes of reperfusion and followed by a final 1 hour period of reperfusion. Normal left circumflex coronary arteries were used as control samples. Repetitive ischemia and reperfusion significantly (p < 0.01) inhibited the relaxation response to acetylcholine in rings preconstricted with potassium. In an additional group of dogs subjected to the same protocol, 10 micrograms of human recombinant TGF-beta 1 was infused into the left anterior descending coronary artery distal to the site of occlusion via a diagonal branch at 0.3 ml/min immediately before and during the repetitive occlusions and reperfusions. TGF-beta 1 prevented impaired endothelium-dependent relaxation after multiple brief occlusions and reperfusions. These results demonstrate a protective role for TGF-beta 1 in the endothelial injury that occurs during repeated episodes of coronary artery occlusion and reperfusion. PMID- 8197969 TI - Conjoint use of MM and MB creatine kinase isoforms in detection of coronary recanalization. AB - To determine whether differences in the kinetics of isoforms of MM and MB creatine kinase affect their ability to detect coronary patency in patients treated with thrombolytic agents, we compared MM and MB isoform profiles in 33 consecutive patients. Results were discordant in 13 of the 33 at 1 hour. When the rates of increase of both isoforms were considered, discordance was present in only 10 of the 33 patients. In five patients %MM3 rose rapidly during the second hour and infarct-related vessels were patent. Four of the five without a rapid increase had occluded infarct-related vessels. These data suggest that criteria based on rates of change in %MB2 are more sensitive than those based on %MM3. However, criteria based on %MM3 are more likely to identify patients in need of interventions to maintain coronary patency. PMID- 8197970 TI - Implications of inferior ST-segment depression in anterior acute myocardial infarction: electrocardiographic and angiographic correlation. AB - This study assesses the significance of inferior ST-segment depression during anterior acute myocardial infarction (AMI) by investigating the relationship between inferior ST-segment depression and (1) the site of the left anterior descending (LAD) coronary artery lesion and (2) ST-segment deviation in the various anterior and lateral leads. We studied 126 patients with anterior AMI who underwent coronary angiography within 21 days of hospitalization. The admission 12-lead electrocardiograms were evaluated for ST-segment amplitude in each lead at 0.08 second after the J-point. Coronary angiography was evaluated for the site and severity of luminal narrowing of the coronary arteries. The site of the culprit lesion in the LAD artery, relative to the origin of the first septal and diagonal branches, was determined. In four patients no lesion was identified in the LAD artery. Of the remaining 122 patients, 40 and 53 patients had a LAD artery lesion proximal to the first septal and first diagonal branches, respectively. Additional luminal narrowing (> or = 70% of diameter) was found in the circumflex and the right coronary arteries in 27 and 37 patients, respectively. ST-segment depression of > 1 mm in leads II, III, and aVF was noted in 24, 29, and 24 patients, respectively. The prevalence of a LAD artery preseptal and prediagonal lesion was higher in patients with inferior ST-segment depression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8197971 TI - Comparison of the distribution of myocardial blood flow between exercise-induced and hyperventilation-induced attacks of coronary spasm: a study with thallium-201 myocardial scintigraphy. AB - Exercise and hyperventilation tests are often used as the provocative tests for coronary artery spasm. To examine the distribution of myocardial blood flow during exercise-induced and hyperventilation-induced attacks of coronary spasm, thallium-201 myocardial scintigraphy was performed in 47 patients with variant angina. The extent and severity scores and severity index (severity score/extent score) of scintigraphic perfusion defect were calculated. In 32 patients, anginal attack associated with ST elevation on the electrocardiogram was induced by exercise; in 23 patients, the attack was induced by hyperventilation. In patients with either anterior or inferior wall ischemia, both the extent and severity scores and severity index in the scintigram were significantly greater in exercise-induced anginal attack than those in hyperventilation-induced attack. In patients with simultaneous anterior and inferior wall ischemia, they tended to be greater in exercise-induced attack. In eight patients in whom anginal attack was induced by both exercise and hyperventilation, these scores and index were significantly greater in exercise-induced attack than those in hyperventilation induced attack. These data suggest that myocardial ischemia during exercise induced attack is enhanced as compared with that during hyperventilation-induced attack. Thallium-201 scintigraphy combined with exercise testing seems to be more sensitive for detecting myocardial ischemia induced by coronary spasm. PMID- 8197972 TI - Ischemia-induced changes in human endocardial electrograms during percutaneous transluminal coronary angioplasty. AB - The electrophysiologic sequelae of acute reversible transmural myocardial ischemia in humans are poorly understood. Experimental models have demonstrated slowing of conduction in ischemic myocardium, but similar evidence in humans is lacking. We used percutaneous transluminal coronary angioplasty as a model for reversible ischemia to (1) analyze the regional endocardial electrogram response to ischemia and (2) determine whether an initial episode of ischemia may mitigate the effects of a subsequent bout of ischemia (preconditioning). We recorded bipolar left ventricular endocardial electrograms during elective angioplasty in 11 patients and examined changes in amplitude and duration on the electrogram. Each of the 11 patients underwent two to seven balloon inflations. The electrogram amplitude at 90 seconds of balloon occlusion fell to 86% +/- 17% of the control value, and the electrogram duration increased to 109% +/- 12% of the control value. These variables returned to baseline values by 30 and 120 seconds, respectively, after balloon deflation. Among the six patients in the preconditioning protocol, the electrogram duration at 90 seconds was less with the second inflation (106% +/- 7%) than with the first (115% +/- 17%, p < 0.05). The difference in electrogram amplitude between the first and the second inflation was not significant (88% +/- 17% vs 85% +/- 13%, p = NS). At 60 seconds of ischemia there was no difference between normal sinus rhythm and paced complexes in the magnitude of change in electrogram amplitude or duration. We conclude that acute transmural myocardial ischemia in humans is associated with a decrease in local bipolar endocardial electrogram amplitude and an increase in electrogram duration. These findings are consistent with slowed conduction in the ischemic zone and are in agreement with experimental findings in animals. Furthermore, a preconditioning effect on electrogram duration suggests a possible protective effect for repeated bouts of ischemia. PMID- 8197973 TI - Color Doppler study of mitral regurgitation during percutaneous transluminal coronary angioplasty. AB - Mitral regurgitation (MR) was evaluated by color Doppler echocardiography during percutaneous transluminal coronary angioplasty (PTCA) in 28 patients with one vessel artery disease (left anterior descending artery in 11, right coronary artery in 8, and circumflex artery in 9) and normal left ventricular function. In all three groups, left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) decreased significantly during artery occlusion in comparison with baseline values (no differences among various groups). Anterior and inferior akinesia/dyskinesia was observed in all patients during left anterior descending and right coronary artery occlusion, respectively. Lateral akinesia/dyskinesia was induced by occlusion of the circumflex artery in six patients (all with proximal lesions [p < 0.05 vs the other two groups]) and the right coronary artery in one. Only the six patients with circumflex artery occlusion showed PTCA related MR (> 2+ in two). LVEF and WMSI were similar during artery occlusion in patients with and without MR. Neither mitral leaflet prolapse nor anulus dilation occurred during PTCA in any of the patients. Our data show that during brief occlusion of the proximal circumflex artery, functional MR (usually mild) frequently occurs in relation to specific lateral akinesia/dyskinesia. PMID- 8197974 TI - Clinical significance of distal embolization after transluminal extraction atherectomy in diffusely diseased saphenous vein grafts. AB - Standard balloon angioplasty of degenerated saphenous vein graft lesions may be complicated by distal embolization, particularly in the presence of intragraft thrombus. Transluminal extraction atherectomy may be useful in this setting because of its ability to remove particulate debris. This study was designed to identify the incidence and prognostic significance of distal embolization after transluminal extraction atherectomy in high-risk saphenous vein graft lesions. To address these issues the clinical course of 65 consecutive patients (86 high-risk saphenous vein graft lesions) was reviewed after extraction atherectomy. Distal embolization occurred in 11 (12.8%) of 86 high-risk lesions. The majority (63.6%) of these episodes occurred after adjunct balloon dilatation following uncomplicated use of the extraction atherectomy catheter. Correlates of distal embolization included patient age and the presence of intragraft thrombus. Major in-hospital complications developed more often in patients with distal embolization (46% vs 2% in those without distal embolization, p < 0.001), resulting in a reduced procedural success rate in this group (55% vs 91%, p = 0.01). We conclude that the risk of distal embolization after saphenous vein graft angioplasty, although potentially reduced, is not eliminated with transluminal extraction atherectomy, particularly in lesions with superimposed thrombus. PMID- 8197975 TI - Clinical and angiographic follow-up after coronary angioplasty in patients with two-vessel disease: influence of completeness and adequacy of revascularization on long-term outcome. AB - To assess the influence of the degree of revascularization on long-term results with angioplasty in multivessel disease, 151 consecutive patients with double vessel disease and successful angioplasty in at least one vessel were prospectively followed up for a mean of 14 months (range 6 to 30 months) with clinical evaluation, an exercise stress test, and routine angiography. Patients were divided into three groups according to completeness and adequacy of revascularization: group 1--complete revascularization (no residual stenosis > or = 70%, 51 patients); group 2--incomplete but functionally adequate revascularization (residual stenosis > or = 70% in a vessel < 2 mm in diameter or supplying akinetic or dyskinetic segments of the left ventricle, 56 patients); group 3--incomplete and inadequate revascularization (residual stenosis > or = 70% in a vessel > or = 2 mm in diameter supplying normal or hypokinetic segments, 45 patients). There were no late deaths; one myocardial infarction occurred in group 1 patients, three in group 2, and two in group 3 patients (p = NS). Recurrence of angina was lower in group 1 (13 of 51 or 26%) and group 2 (16 of 56 or 28%) compared with group 3 (23 of 45 or 51%, p < 0.01). A positive stress test for ischemia was present in 20 patients (39%) of group 1, in 30 (54%) of group 2, and in 26 patients (58%) of group 3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8197976 TI - Dobutamine stress echocardiography: sensitivity, specificity, and predictive value for future cardiac events. AB - We conducted a retrospective study to determine whether dobutamine stress echocardiography (DE) can be used for risk stratification of patients with known or suspected coronary artery disease (CAD). The study population consisted of 77 patients who underwent DE at our institution. The protocol consisted of an echocardiogram at baseline followed by imaging during intravenous dobutamine infusion starting at 10 micrograms/kg/min with increments of 10 micrograms/kg/min every 3 minutes to a maximum dose of 40 micrograms/kg/min. The reasons for performing DE included preoperative cardiac evaluation (30), chest pain (23), assessment of ischemia (18), and suspected restenosis (6). DE was classified according to wall motion response as normal (before and during DE), fixed abnormal (abnormal before with no change during DE), or ischemic (new wall-motion abnormality during DE). Mean duration of follow-up was 10 months. Cardiac events occurred in 14 patients. These included congestive heart failure in seven patients, myocardial infarction in six, and cardiac death in one. A normal wall motion response (n = 40) was associated with a low incidence of cardiac events (5%), whereas 5 of 10 patients (50%) with an ischemic response had events. The risk of cardiac events was intermediate (26%) in patients with fixed abnormal wall motion. Overall sensitivity of DE for predicting future cardiac events was 85%. In 45 patients who underwent coronary angiography within 2 months of DE, the test detected CAD with a sensitivity of 71%. In conclusion, the wall-motion response during DE may be used for identifying patients at high risk for future cardiac events. PMID- 8197977 TI - Comparison of thallium-201 single-photon emission computed tomographic scintigraphy with intravenous dipyridamole and arm exercise. AB - In patients who cannot perform treadmill exercise, both intravenous dipyridamole and arm exercise have been used with thallium-201 scintigraphy to detect significant coronary artery disease. However, no study has directly evaluated the results of intravenous dipyridamole and arm exercise thallium scintigraphy as compared with coronary angiography. It was the purpose of this study to compare intravenous dipyridamole and arm exercise thallium-201 single-photon emission computed tomographic (SPECT) scintigraphy for detection of significant coronary artery disease in patients who could not perform treadmill exercise. Data are presented for both intravenous dipyridamole and arm exercise thallium-201 SPECT scintigraphy in 18 men who could not perform treadmill exercise, and results are compared with those of coronary angiography. Ten of 11 (91%) patients with significant coronary artery disease were identified correctly, and the results of intravenous dipyridamole and arm exercise thallium scintigraphy were comparable. In patients without significant coronary artery disease, intravenous dipyridamole thallium images were interpreted correctly. However, initial arm exercise thallium images demonstrated a fixed inferior wall defect in two of seven patients without significant coronary artery disease. Images in one of these patients could not be retrieved from tape for further analysis. Review of the images in the other patient demonstrated relatively high background radioactivity, and when the images were displayed without background subtraction, the inferior wall was correctly interpreted as normal. We conclude that results of intravenous dipyridamole and arm exercise thallium-201 SPECT scintigraphy are comparable. PMID- 8197978 TI - Diagnostic and prognostic accuracy of the exercise electrocardiogram in patients with preexisting right bundle branch block. AB - The value of exercise testing in patients with right bundle branch block (RBBB) is uncertain. A retrospective review of 3609 patients who underwent exercise testing identified 163 (4.5%) with preexisting RBBB. After excluding those with coronary artery bypass graft(s), 133 patients remained and 48 (36%) had a prior myocardial infarction. Angiograms were available for 30 (23%) patients. After a mean follow-up of 33 +/- 23 months, seven patients had a fatal or nonfatal myocardial infarction. Twenty five (19%) patients had > or = 1 mm of non upsloping ST depression in leads V5 or V6. With angiographic disease or previous myocardial infarction used as endpoints of coronary artery disease, the exercise test had a sensitivity of 27% (15/56), a specificity of 87% (67/77), and a predictive accuracy of 62% (82/133), (chi 2 = 4.04, p = 0.04). There were 24 deaths, a 10% annual mortality rate. Univariate analysis of clinical, exercise, and angiographic data revealed that nonsurvivors had a lower peak systolic blood pressure, a lower exercise capacity in METS, and a higher prevalence of coronary artery disease (p = 0.0001, p = 0.02, p = 0.03, respectively). Left ventricular ejection fraction and the amount of additional ST depression during exercise did not differ significantly (p = NS). Receiver operating characteristic curve analysis revealed that systolic blood pressure (area = 0.741, z = 5.22, p < 0.001) and exercise capacity (area = 0.66, z = 3.12, p = 0.009) were predictive of mortality, whereas additional ST depression during exercise (area = 0.588, z = 0.70, p = 0.24) was not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8197979 TI - Prevalence of fluoroscopic coronary calcific deposits in high-risk asymptomatic persons. AB - Coronary calcific deposits are always associated with coronary atherosclerosis. Sensitive radiographic technology can detect coronary calcium before atherosclerosis becomes symptomatic. A total of 1461 asymptomatic high-risk adult subjects were studied with digital subtraction fluoroscopy to detect coronary calcium. Risk factor data were recorded including age, sex, family history, smoking history, diabetes history, body mass index, systolic blood pressure, left ventricular hypertrophy on ECG, total serum cholesterol level, high-density lipoprotein (HDL) cholesterol, and total cholesterol/HDL ratio. Digital subtraction fluoroscopy in the left anterior oblique projection was performed in all subjects. The prevalence of calcific deposits in at least one major coronary artery was high (58.3%). Eleven percent had coronary calcium in all three major arteries. Multivariate logistic regression analysis showed significant correlations (p < 0.05) between the prevalence of coronary calcium and age, smoking history (relative risk = 1.30), diabetes history (relative risk = 1.24), and family history (relative risk = 1.26). In older subjects (at least 65 years of age), smoking and serum lipoproteins assumed greater importance as contributors to coronary calcium, whereas in younger subjects a history of diabetes was more significant. Coronary calcific deposits are prevalent in high risk asymptomatic subjects. Their occurrence is closely related to most known risk factors. PMID- 8197980 TI - Safety of radiofrequency catheter ablation of accessory atrioventricular pathways. AB - The acute anatomic and valvular consequences of radiofrequency catheter ablation of accessory pathways were evaluated in 62 patients by means of serial echocardiographic examinations. Semiquantitative assessment of valvular incompetence and classification into one of four grades according to the width and the extension of the jet from the valvular orifice were carried out. Segmental wall motion abnormalities were evaluated semiquantitatively with four grades of severity (normal, hypokinesia, akinesia, or dyskinesia). New echocardiographic abnormalities were observed in five patients. One thrombus on the ventricular aspect of the mitral valve, three hemodynamically insignificant pericardial effusions, and one increase in severity of tricuspid incompetence were found 1 day after radiofrequency catheter ablation. We conclude that echocardiographic changes after radiofrequency ablation of accessory pathways are rare and of minor significance. These findings confirm the safety of the procedure. PMID- 8197981 TI - Marked action potential prolongation as a source of injury current leading to border zone arrhythmogenesis. AB - The objective of this study was to delineate electrophysiologic phenomena in a border zone adjacent to a zone of marked action potential prolongation. By means of a standard microelectrode technique, we studied sheep Purkinje fibers placed in a partitioned chamber and superfused with Tyrode's solution. Ethylenediamine tetraacetic acid (EDTA) was added to one chamber. Recordings were made in the abnormal segment (ABN) superfused with EDTA and at two sites in the normal segment (NL)--at the border within 0.5 mm (NL-B) and 3 to 4 mm from the partition (NL-D). Exposure of ABN to EDTA caused marked prolongation of the action potential duration (APD) and triggered activations (TAs), which were found to have the earliest recorded activation at NL-B (n = 20), at ABN (n = 8), or at both sites (n = 12). NL-B recordings displayed prolonged low-amplitude secondary plateaus, which were termed "border zone early afterdepolarizations." These were coincident with the plateaus of the prolonged action potentials in ABN and appeared to be due to electrotonic transmission of current from ABN to NL-B. Border zone TAs arose from these low-amplitude plateaus and were either eliminated by the addition of lidocaine to NL consistent with their presumed NL site of origin or occurred after localized withdrawal of EDTA from one segment in fibers rendered quiescent at the plateau by generalized superfusion with EDTA. In conclusion, APD and membrane potential inhomogeneities lead to electrotonic transmission of injury current to border zones adjacent to zones of abnormal APD prolongation. This injury current leads to TAs originating at the border zone. These findings may be relevant to the role of injury current in clinical arrhythmias. PMID- 8197983 TI - Mitral balloon valvotomy in children with Inoue balloon technique: immediate and intermediate-term result. AB - Percutaneous mitral balloon valvotomy (PMV) using the Inoue balloon technique was attempted in 170 patients. Of these, 30 patients were children aged 10 to 18 years (mean 15.9 +/- 2.7 years). There were 16 female and 14 male patients. All were in sinus rhythm. The procedure was successful in 28 patients (93%). PMV was performed using 20 to 28 mm (mean 25 mm) diameter balloon catheters with an echo Doppler guided stepwise mitral dilation technique. After PMV, the mean left atrial pressure decreased from 25 +/- 5 to 14 +/- 4 mm Hg (p < 0.001). The mean mitral valve gradient (MVG) decreased from 16 +/- 4 to 6 +/- 3 mm Hg (p < 0.001). The mitral valve area (MVA) by catheter increased from 0.7 +/- 0.2 to 1.7 +/- 0.5 cm2 (p < 0.001), and MVA as determined by echocardiography (2DE) increased from 0.8 +/- 0.1 to 1.9 +/- 0.3 cm2 (p < 0.01). There were no deaths or thromboembolic complications; cardiac tamponade developed in one patient, mild mitral regurgitation (MR) developed in three patients (10%) and increased by one grade from (1+ to 2+) in another two patients (8%). A small atrial septal defect (ASD) assessed by color flow mapping developed in seven patients (25%); 90% were closed at 3 months. The Doppler and 2DE MVAs were maintained at 1.8 +/- 0.4 cm2 at 17 months' mean follow-up; one patient developed restenosis. We conclude the PMV using the Inoue balloon catheter is safe and effective in the treatment of severe mitral stenosis in children, with a low complication rate. PMID- 8197982 TI - Influence of subvalvular fibrosis on results and complications of percutaneous mitral commissurotomy with use of the Inoue balloon. AB - In 136 consecutive patients who underwent percutaneous transvenous mitral commissurotomy (PTMC) with use of the single rubber-nylon (Inoue) balloon Inoue balloon angiographically analyzed subvalvular fibrosis was assessed retrospectively with regard to results and complications. There were 53 males and 83 females, with a mean age of 22 +/- 11 years (range 10 to 48 years). For the entire group, mitral valve area increased from 0.7 +/- 0.3 to 2.1 +/- 0.6 cm2 (p < 0.001). Valve area increased from 0.7 +/- 0.12 to 1.8 +/- 0.14 cm2 in patients with severe subvalvular fibrosis (n = 55) and from 0.8 +/- 0.11 to 1.9 +/- 0.12 cm2 in cases with mild to moderate subvalvular fibrosis (n = 80; p = NS). The number of patients with 2+ or greater increase in mitral regurgitation was not different between the two groups (6% vs 5.5%, p = NS). None of the patients required mitral valve replacement immediately after PTMC. We conclude that, with use of the Inoue balloon, PTMC can be successfully performed in patients with severe subvalvular fibrosis. PMID- 8197984 TI - Angle of incidence does not affect accuracy of mitral stenosis area calculation by pressure half-time: application to Doppler transesophageal echocardiography. AB - Continuous wave Doppler transesophageal echocardiography (TEE) may allow the estimation of stenotic mitral valve area. Intuitively the posterolateral position of the transducer appears to limit the application of TEE for this purpose because of the excessive angle of incidence to mitral valve inflow. However, algebraic equations can be used to predict that the angle of incidence should not affect mitral valve area derived by using pressure half-time. To test the validity of this prediction and the potential application of Doppler TEE to estimate mitral valve area, 28 patients (21 women, 7 men) with a mean age of 59 +/- 14 years with mitral stenosis were studied by continuous wave transthoracic echocardiography (TTE) and TEE guided color flow Doppler. TTE was performed from the apical four-chamber (TEE-0) and a modified parasternal four-chamber (TTE-MAL) plane as a means of intentionally increasing the angle of incidence. TEE was done by using the horizontal (TEE-HAX) and vertical (TEE-VAX) planes. Mitral valve area was calculated by pressure half-time method. Mean mitral valve area did not differ (p = not significant [NS]) between TTE-0 (1.26 +/- 0.84 cm2), TTE-MAL (1.37 +/- 0.94 cm2), TEE-HAX (1.39 +/- 0.92 cm2), and TEE-VAX (1.35 +/- 0.89 cm2). The estimated mean angle of incidence during TTE-MAL was 45 +/- 12 degrees (range 21 to 68 degrees). Six (21%) of 28 and 9 (32%) of 28 patients had an underestimation of transmitral peak velocities with TEE from the horizontal or vertical planes, respectively. However, excellent correlations were found between mitral valve area derived by using TEE-0 versus TTE-MAL (r = 0.97; SEE = 0.25 cm2; intercept = 0.02 cm2; slope = 1.08; and p = 0.0001), TEE-HAX (r = 0.91; SEE = 0.39 cm2; intercept = 0.14 cm2; slope = 1.00; and p = 0.0001) and TEE-VAX (r = 0.92; SEE = 0.36 cm2; intercept = 0.13 cm2; slope = 0.97; and p = 0.0001). These results are directly applicable to Doppler TEE in the determination of mitral stenosis area by pressure half-time, whereby 21% to 32% of patients using the horizontal or vertical transesophageal planes may have a significant angle of incidence leading to underestimation of transmitral valve velocities. Future studies comparing Doppler TEE with cardiac catheterization are of interest. However, the present study suggests that Doppler TEE will play an important role in the hemodynamic assessment of the severity of mitral valve stenosis. PMID- 8197985 TI - Exercise Doppler echocardiography identifies abnormal hemodynamics in adults with congenital heart disease. AB - The hemodynamic factors contributing to reduced exercise capacity in adults with congenital heart disease are not fully defined. We hypothesized that they would demonstrate reduced exercise capacity compared with age-matched control subjects because of abnormal exercise hemodynamics and ventricular performance demonstrable by echocardiography. We retrospectively analyzed the results of all studies in all patients with congenital heart disease (from 1988 to 1993) and found that the peak work load and double product achieved were decreased in comparison with normal values (79 +/- 47 W vs 149 +/- 52 W [p < 0.0001] and 19,210 +/- 6805 vs 25,701 +/- 6440 [p = 0.005], respectively). Seven patients achieved work loads < 40 W associated with an exaggerated exercise pulmonary artery pressure response, decreases in right and/or left ventricular function with exercise, or both. Normal or near-normal exercise tolerance was observed in the following patient groups: (1) repaired tetralogy of Fallot, (2) uncomplicated I-transposition of the great arteries, and (3) Ebstein's anomaly with atrial septal defect. We conclude that exercise echocardiography provides new hemodynamic information for evaluating functional limitations in congenital heart disease. PMID- 8197986 TI - Effect of orthotopic cardiac transplantation on peripheral vascular function in congestive heart failure: influence of cyclosporine therapy. AB - The objective of this study was to examine peripheral vascular function before and after cardiac transplantation and to assess the effect of immunosuppressive therapy on peripheral vascular reactivity. Peripheral vascular function abnormalities present in congestive heart failure may be reversed with cardiac transplantation, but immunosuppressive therapy may alter these changes in the peripheral vasculature. Venous occlusion plethysmography was used to study peripheral vascular function in nine patients with severe congestive heart failure who underwent cardiac transplantation. Forearm blood flow and forearm vascular resistance were measured in patients with congestive heart failure in response to cold stimulation, maximal hyperemia, and hand grip exercise (1) before transplantation; (2) 24 to 36 hours posttransplantation before the commencement of cyclosporine; (3) 6 to 8 days posttransplantation in the presence of therapeutic cyclosporine levels; and (4) 6 weeks posttransplantation. Venous capacitance was also measured. After cardiac transplantation, mean arterial pressure increased and remained elevated. Forearm blood flow initially increased after transplantation but subsequently decreased with cyclosporine. Cold-induced reflex sympathetic activation decreased immediately after transplantation but was significantly enhanced with cyclosporine. The maximal vasodilatory response following ischemic cuff occlusion and with 5 minutes of isometric hand grip exercise increased significantly after transplantation and remained improved at 6 weeks. Thus after cardiac transplantation, peripheral vasodilator function improves and is not altered by cyclosporine. However, with cyclosporine therapy resting forearm vascular resistance increases and reflex sympathetic vasoconstriction is enhanced, suggesting that cyclosporine may potentiate adrenergic-mediated peripheral vasoconstriction and thus may contribute to posttransplant hypertension. PMID- 8197987 TI - Coronary arteries in unstable angina pectoris, acute myocardial infarction, and sudden coronary death. PMID- 8197988 TI - Intranasal delivery of cardiovascular agents: an innovative approach to cardiovascular pharmacotherapy. AB - The intranasal administration of drugs has long been used for the topical treatment of various nasal disorders. Many features of the intranasal mucosa also make it useful for delivery of systemically active agents. It has been shown that intranasal drug administration can provide plasma drug levels similar to those observed with comparable doses of parenteral drugs. The feasibility of intranasal administration of propranolol, nifedipine, and nitroglycerin has been investigated in several small clinical studies. Intranasal propranolol has been shown to improve exercise tolerance in patients with angina pectoris. Intranasal nifedipine has been used to treat patients with perioperative hypertension and hypertensive crisis. Intranasal administration of nitroglycerin was shown to blunt the hypertensive response to endotracheal intubation. These studies and others suggest that intranasal delivery of cardiovascular drug treatment could be used in those clinical situations where a rapid or intermittent drug effect is desired and can potentially serve as an alternative to parenteral drug administration. PMID- 8197989 TI - Acute procedural results in the treatment of 30 coronary artery bifurcation lesions with a double-wire atherectomy technique for side-branch protection. AB - Percutaneous treatment of bifurcation lesions has been consistently shown to be associated with lower acute success rates, higher initial complication rates, and an increased rate of restenosis when compared with findings in nonbifurcation lesions. Recent analysis of data from a CAVEAT subgroup suggests that directional atherectomy of bifurcation lesions can improve initial success rates and lower restenosis rates but at the cost of high complication rates. Reports from several angioplasty series document improved success rates and lower complication rates with the use of a two-wire technique to protect side branches when treating bifurcation lesions. Our experience with a two-wire atherectomy technique that uses a nitinol wire to protect important side branches is presented. PMID- 8197991 TI - Temperature-guided radiofrequency catheter ablation of closed-chest ventricular myocardium with a novel thermistor-tipped catheter. AB - Successful lesion formation using radiofrequency energy requires adequate tissue heating. Temperature monitoring during ablation may thus improve the efficiency of radiofrequency catheter ablation. Each of five anesthetized, closed-chest adult mongrel dogs weighing 19 to 24 kg received a single pulsed ablation at four left ventricular and two right ventricular sites using a thermistor-tipped 2 mm electrode catheter. The maximum temperature at the electrode-tissue interface was preset at 90 degrees C and current delivered for 40 seconds (method A) or at 70 degrees C for 40 seconds (method B1) or 80 seconds (method B2). With method C, the temperature was set at 90 degrees C for 20 seconds, after which the temperature setting was turned off and ablation continued until impedance increased or the temperature reached > or = 100 degrees C. The size of the resultant lesion was greater with method A than with methods B1, B2 or C (mean length x width x depth, 5.6 x 4.8 x 6.5 vs 4.1 x 4.0 x 5.1 vs 4.2 x 4.0 x 5.2 vs 5.0 x 4.3 x 5.7 mm, respectively; p < 0.01). There was no significant difference in lesion size between pulse durations of 40 seconds (group B1) and 80 seconds (group B2). Only two ablations, both in the anteroapical right ventricle, resulted in a marked rise in impedance without the temperature reaching > or = 100 degrees C. We conclude that temperature (and thus impedance) monitoring improves control and efficacy of lesion formation during radiofrequency catheter ablation. PMID- 8197990 TI - Long-term intraindividual cholesterol variability: natural course and adverse impact on morbidity and mortality--the Framingham Study. AB - We examined intraindividual variability in serum TC in 2912 men and women having TC measured at each of biennial examinations 2 through 7 of the FHS. RMSE described variability around the linear slope of an individual's TC during the baseline decade. Average biennial difference +/- SD was +3.7 +/- 6.7 mg/dl in men, +6.6 +/- 8.8 mg/dl in women. RMSE was < 7 mg/dl in half the group, but in the teens and twenties in the highest quartile of variability. Age-adjusted analyses showed positive associations with all-cause mortality over a 24-year period in men and a positive relation to cardiovascular and coronary incidence and mortality in both sexes. Risk ratios for highest versus lowest quartile of TC variability ranged up to 1.75. High TC variability portends excess mortality risk, and women in particular must include TC variability among their risk factors for coronary death. PMID- 8197992 TI - Vasovagal syncope as a cause of motor vehicle accidents. PMID- 8197993 TI - Coronary sinus septal defect mimicking left atrial membrane. PMID- 8197994 TI - Recurrent malignant fibrous histiocytoma of the left atrium with extracardiac extension. PMID- 8197995 TI - Quiescent left atrial myxoma. PMID- 8197996 TI - Syndrome of combined aortic and pulmonary valve stenosis: successful treatment with balloon dilatation. PMID- 8197997 TI - Chylothorax, splenic lymphangiomatosis, and consumptive coagulopathy after surgical treatment of primary chylopericardium. PMID- 8197998 TI - Increased plasma levels of brain natriuretic peptide in patients with isolated diastolic dysfunction. PMID- 8197999 TI - Acute hepatic injury after treatment with diltiazem. PMID- 8198000 TI - Transesophageal echocardiographic diagnosis of massive pulmonary embolism during cardiopulmonary resuscitation. PMID- 8198002 TI - Variable effect of anticoagulation in the treatment of severe protruding atherosclerotic aortic debris. PMID- 8198001 TI - Pulmonary embolectomy for intravenous uterine leiomyomatosis. PMID- 8198003 TI - Recurrence of left atrial ball thrombus after surgical thrombectomy. PMID- 8198004 TI - Serial arteriographic findings in a patient with development of an unusually large coronary aneurysm after angioplasty. PMID- 8198005 TI - Silent ischemia preceding sudden cardiac death in a patient after vascular surgery. PMID- 8198006 TI - QT-interval dispersion on 12-lead electrocardiogram in normal subjects: its reproducibility and relation to the T wave. PMID- 8198007 TI - Radiofrequency ablation in a patient with tachycardia incorporating triple free wall accessory pathways and atrioventricular nodal reentrant tachycardia. PMID- 8198008 TI - Coronary flow after thrombolysis. PMID- 8198009 TI - Clinically silent patent ductus arteriosus. PMID- 8198010 TI - Discrete subaortic stenosis. PMID- 8198011 TI - Bedside pulmonary artery catheterization. PMID- 8198012 TI - Right ventricular infarction with right bundle block branch. PMID- 8198013 TI - Atrial fibrillation from liquid protein diet. PMID- 8198014 TI - Cardiovascular effects of nicotine: relation to deleterious effects of cigarette smoking. PMID- 8198015 TI - On the matter of method in exercise testing. PMID- 8198016 TI - Exercise and congenital heart disease. PMID- 8198017 TI - Hydroxymethylglutaryl coenzyme a reductase inhibition: fluvastatin, a clinical investigators' update. Introduction. PMID- 8198018 TI - Clinical implications of the biopharmaceutical properties of fluvastatin. AB - Fluvastatin sodium (Lescol; Sandoz) the first entirely synthetic 3-hydroxy-3 methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor studied, is structurally distinct from the other HMG-CoA reductase inhibitors currently available, all of which are fungal metabolites and analogues of compactin. Fluvastatin's distinct structure may be responsible for the biopharmaceutical properties that result in its low systemic exposure and, subsequently, low incidence of peripheral adverse events, such as headache and myositis. Fluvastatin is rapidly absorbed from the gastrointestinal tract; has a 30-minute half-life, the shortest of any currently available HMG-CoA reductase inhibitor (lovastatin, 15 hours; pravastatin, 2 hours; simvastatin, 15.6 hours); is highly selective for the liver, undergoing extensive first-pass metabolism; has no active circulating metabolites; and does not penetrate the blood-brain barrier, unlike lovastatin and simvastatin. The low systemic exposure suggests that the occurrence of peripheral adverse events, such as myositis, central nervous system effects, and drug-drug interactions, may be less than what is currently observed with other HMG-CoA reductase inhibitors. Neither niacin nor propranolol had an effect on fluvastatin plasma levels when combined with fluvastatin. In contrast to other HMG-CoA reductase inhibitors, fluvastatin in combination with niacin resulted in no instances of myositis or other serious adverse events. Although the interaction of fluvastatin with cholestyramine resulted in a lower rate and extent of fluvastatin bioavailability, this reduction had no impact on clinical efficacy. Fluvastatin administered to patients chronically receiving digoxin had no effect on the area under the curve (AUC) of digoxin compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198019 TI - Updated clinical safety experience with fluvastatin. AB - Clinical experience with fluvastatin in > 1,800 North American patients treated for an average of 61 weeks has shown it to be safe and well tolerated. Frequencies of transaminase and creatine kinase elevations compare favorably with those observed during long-term administration of other 3-hydroxy-3 methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Further, whereas frank rhabdomyolysis has been encountered with treatment with all other HMG-CoA reductase inhibitors, this syndrome has not been observed to date with fluvastatin in studies here or abroad; a single case of myopathy, which was probably related to physical exertion, was reported in a patient receiving fluvastatin. Although dyspepsia was observed more commonly in fluvastatin patients the incidence, along with that of other adverse events (e.g., headache), and the number of treatment discontinuations proved statistically indistinguishable from those of placebo controls. Whether the favorable safety profile of fluvastatin is related to this synthetic agent's unique biopharmaceutical profile is a matter of ongoing long-term inquiry. PMID- 8198020 TI - Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety. AB - A double-blind, randomized study was undertaken to evaluate the efficacy and safety of fluvastatin as monotherapy and as combination therapy with niacin in the treatment of hypercholesterolemia refractory to diet. Seventy-four patients with plasma low-density lipoprotein cholesterol (LDL-C) levels > or = 160 mg/dL were treated with fluvastatin, 20 mg/d, or placebo for 6 weeks. Thereafter, immediate-release niacin, at a dosage titrated to a maximum of 3 g/d, was added to both regimens for another 9 weeks. All adverse events were monitored, with particular attention to the evaluation of liver and muscle enzymes. Initial analysis of the data shows that fluvastatin and its combination with niacin was well tolerated and was not associated with any serious adverse events. Small, transient, asymptomatic rises in aspartate aminotransferase (AST) occurred in 28.9% of fluvastatin-niacin treated patients compared to 8.3% in the niacin placebo control arm (p < 0.05). These were considered clinically insignificant in that no transaminase elevations > 3 times the upper limit of normal occurred. No evidence of myopathy, creatine kinase levels exceeding 10 times the upper limit of normal, myositis, or rhabdomyolysis were demonstrated in this short-term trial. The majority of adverse events resulting in patient withdrawals were ascribed to niacin therapy and included cutaneous vasodilatation, flushing, itching, and rash. These preliminary results suggest that fluvastatin, both alone and combined with niacin, is an effective, safe, and well-tolerated treatment for hypercholesterolemia. PMID- 8198021 TI - Comparison of properties of four inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase. AB - Four inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase have been approved for treatment of hypercholesterolemia. Three of these are fungal metabolites or derivatives thereof: lovastatin, simvastatin, and pravastatin. The fourth, fluvastatin, is totally synthetic. Its structure, containing a fluorophenyl-substituted indole ring, is distinct from that of the fungal metabolites. Lovastatin and simvastatin are administered as prodrugs, which undergo in vivo transformation to active inhibitory forms; fluvastatin and pravastatin are administered as active agents. The HMG-CoA reductase inhibitors are all effective in reducing plasma concentrations of low density lipoprotein. They have differing pharmacokinetic properties, which may be of importance in some patients. All of these drugs are very well tolerated, and there do not appear to be major differences in toxicity or adverse effects. When LDL reductions > 30% are needed, simvastatin is the most cost-effective HMG-CoA reductase inhibitor. However, these drugs are most commonly used in dosages that reduce LDL-C by 20-30%. For this degree of LDL reduction, fluvastatin is the most cost-effective HMG-CoA reductase inhibitor. PMID- 8198022 TI - Fluvastatin in familial hypercholesterolemia: a cohort analysis of the response to combination treatment. AB - A recent randomized, double-blind, double-dummy trial revealed differences in the response of patients with heterozygous familial hypercholesterolemia to combination therapy with the new, wholly synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin, 20 mg/day and then 40 mg/day, plus the fibric acid analogue bezafibrate, 400 mg/day, vs combination therapy with fluvastatin, 40 mg/day, plus the bile acid sequestrant (resin) cholestyramine, 8 g/day. The main purpose of the present cohort analysis was to determine whether these differences in lipid response were related to imbalances in the patients' prior responses to up to 42 weeks of fluvastatin monotherapy, 20 mg/day, 40 mg/day, and, in some patients, 60 mg/day, in 2 earlier studies. For the present analysis, we identified 18 patients in the fluvastatin plus bezafibrate group (cohort 1) and 16 patients in the fluvastatin plus cholestyramine group (cohort 2) for whom complete dose-response data were available for the full 56-week duration of all 3 studies. Subsets of 7 patients in cohort 1 and 8 patients in cohort 2 had received the 60 mg/day fluvastatin dose during a previous monotherapy study. In cohort 1, low density lipoprotein cholesterol (LDL-C) decreased by 19% with 20 mg/day fluvastatin, by 27% with 40 mg/day fluvastatin, by 31% with 20 mg/day fluvastatin plus bezafibrate, and by 35% with 40 mg/day fluvastatin plus bezafibrate, and the LDL-C/high density lipoprotein cholesterol (HDL-C) ratio had fallen by 46% at the end of combination therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198023 TI - Efficacy and safety of fluvastatin in patients with non-insulin-dependent diabetes mellitus and hyperlipidemia: preliminary report. AB - This randomized, double-blind, placebo-controlled study was designed to evaluate the effect of fluvastatin on the lipid profiles of patients with hypertriglyceridemia resulting from non-insulin-dependent diabetes mellitus (NIDDM). Sixty-six NIDDM patients (24 men, 42 women) with low density lipoprotein cholesterol (LDL-C) levels > 3.36 mmol/liter (130 mg/dL) and triglyceride (TG) levels of 2.3-11.3 mmol/liter (200-1,000 mg/dL) after an 8-week period of Step I diet were given fluvastatin, 20 mg every PM for 6 weeks followed by 20 mg twice daily for an additional 6 weeks, or placebo. By weeks 9-12, fluvastatin decreased plasma LDL-C levels by 24.3% (p < 0.001) and plasma TG by 15.3% (p < 0.01). High density lipoprotein cholesterol levels increased by 4.6% over the same interval (p < 0.05). Fluvastatin treatment was not associated with abnormalities in the indices of glycemic control or clinically important abnormalities in laboratory values. Fluvastatin is an effective treatment of combined elevations of TG and LDL-C in NIDDM. PMID- 8198024 TI - Baseline characteristics of subjects in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) with fluvastatin. AB - A total of 429 subjects (79 women and 350 men), aged 35-75 years, have been enrolled in a randomized clinical trial of fluvastatin therapy for hypercholesterolemia. The progression and regression of atherosclerotic lesions will be assessed by quantitative angiography and positron emission tomography (PET) after 2.5 years of treatment. Patients were included in the trial if they had angiographically documented lesions that occluded 30-75% of the diameter of a major coronary vessel. Of the 429 subjects, 99 were also studied by PET at rest and during static exercise of sustained handgrip combined with administration of dipyridamole. All subjects were instructed in an American Heart Association/National Cholesterol Education Program (AHA/NCEP) Step I or Step II diet. Of the total, 107 subjects (25%) had low density lipoprotein cholesterol (LDL-C) > or = 160 mg/dL and were given cholestyramine, 8 g/day. All subjects were randomized to placebo or fluvastatin, the newest 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor to be introduced into the U.S. market. Fluvastatin is entirely synthetic and is similar in efficacy to the other available HMG-CoA reductase inhibitors. Its pharmaceutical profile (i.e., low systemic exposure) makes fluvastatin a good candidate for use in combination lipid-lowering therapy. The majority of subjects were recruited through a community campaign and the remainder through cardiac catheterization laboratories and the medical records of hospitals in the Texas Medical Center. Approximately 8,500 prospects from the community campaign were screened and 272 were randomized, a conversion rate of approximately 3%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198025 TI - Prevention of restenosis after coronary balloon angioplasty: rationale and design of the Fluvastatin Angioplasty Restenosis (FLARE) Trial. The FLARE Study Group. AB - Prevention of restenosis after successful percutaneous transluminal coronary balloon angioplasty (PTCA) continues to present the greatest therapeutic challenge in interventional cardiology. Experimental and pathological studies describe restenosis as no more than the biologic healing response to arterial injury. Studies of serial quantitative coronary angiography have demonstrated that this biologic process may be measured as the loss in minimal luminal diameter (MLD) from post-PTCA to follow-up angiography and that it is essentially ubiquitous and normally distributed. Thus, quantitative coronary angiography has become the gold standard for evaluation of the angiographic outcome of clinical trials of new agents and devices aimed at prevention of restenosis. The 3-hydroxy 3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors inhibit biosynthesis of mevalonate, a precursor of non-sterol compounds involved in cell proliferation, and thus may control the neointimal response, which forms the kernel of restenosis. Experimental evidence suggests that fluvastatin may exert a greater direct inhibitory effect on proliferating vascular myocytes than other HMG-CoA reductase inhibitors, independent of any lipid-lowering action. The Fluvastatin Angioplasty Restenosis (FLARE) Trial was conceived, in collaboration between the Thoraxcenter, Erasmus University, Rotterdam, The Netherlands, and Sandoz Pharma, to evaluate the ability of fluvastatin 40 mg twice daily to reduce restenosis after successful single-lesion PTCA. Treatment of suitable patients begins 2 weeks before PTCA and continues after successful PTCA (residual diameter stenosis < 50%, without major cardiac complications) to follow-up angiography at 26 +/- 2 weeks. Restenosis is measured by quantitative coronary angiography at a core laboratory as the loss in MLD from post-PTCA to follow-up angiography. It is calculated (90% power, alpha = 0.05) that 730 evaluable patients will be needed to test the hypothesis that fluvastatin will reduce the expected post-PTCA loss in MLD by 40%. Serial lipid analysis will be carried out at a central laboratory. Trial evaluation is focused on the primary endpoint (change in MLD) but includes primary clinical endpoints (death, myocardial infarction, or the need for coronary artery bypass graft surgery or reintervention up to 40 weeks after PTCA) as well as secondary and tertiary clinical, angiographic, and laboratory endpoints. According to this methodologic approach, the effect of fluvastatin in luminal renarrowing and clinical events after successful PTCA as well as possible associations of lipid parameters with restenosis can be comprehensively investigated. PMID- 8198026 TI - Prevention of restenosis after percutaneous transluminal coronary angioplasty by reducing lipoprotein (a) levels with low-density lipoprotein apheresis. Low Density Lipoprotein Apheresis Angioplasty Restenosis Trial (L-ART) Group. AB - This study was designed to test the hypothesis that high plasma lipoprotein (a) (Lp[a]) levels are associated with an increase incidence of restenosis after angioplasty. Elective transluminal coronary angioplasty was performed in 66 patients (58 men and 8 women) aged 57 +/- 9 years (mean +/- SD). Two days before and 5 days after angioplasty, all patients underwent low-density lipoprotein (LDL) apheresis with a dextran sulfate cellulose column as an Lp(a) absorbent; 39 patients also received 10 mg of pravastatin and 1,500 mg of niacin daily. Restenosis was defined as a recurrent luminal stenosis of > or = 50% in a previously dilated segment. Median Lp(a) levels were reduced from 23.3 mg/dl before apheresis to 10.9 mg/dl after apheresis (p < 0.0001). Angiography performed 2 to 9 months after angioplasty revealed restenosis in at least 1 site in 38% of the 137 control patients and in 32% of the 66 patients who underwent apheresis. Restenosis also occurred in 37% of the patients who underwent apheresis alone and in 28% of the patients who also received pravastatin and niacin in combination with LDL apheresis. The restenosis rate was 21% in the 42 patients whose Lp(a) levels were significantly reduced > or = 50%, and in 50% of the 24 patients whose Lp(a) levels were significantly reduced < 50% (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198027 TI - Late results of percutaneous transluminal coronary angioplasty of two or more major native coronary arteries. AB - Of 613 consecutive patients with multivessel coronary artery disease (CAD) undergoing revascularization, 521 patients (85%) underwent primary management with percutaneous transluminal coronary angioplasty (PTCA). To examine long-term outcome in a series of patients often referred for coronary artery bypass graft (CABG) surgery, all patients undergoing multivessel dilations were identified for late follow-up analysis (n = 161). Mean age was 65 years; 54 patients (34%) were women. Four hundred fifty-five of 502 lesions (90.6%) were successfully dilated. Major in-hospital procedural complications occurred in 6 patients (3.7%), including death in 3 (1.9%), nonfatal Q-wave myocardial infarction in 2 (1.2%), and CABG in 1 (0.6%). Final follow-up data were available in 159 patients (99%) at a mean of 39 +/- 18 months. Including in-hospital events, actuarial 3-year survival was 93%, and 3-year infarct-free survival was 90%. At final follow-up, 143 of 146 patients alive (98%) were angina free. Crossover to CABG was required in 25 patients (16%). Repeat PTCA was performed in 67 patients (42%) (mean 1.7 PTCAs/patient, range 1 to 7). PTCA is an effective therapeutic alternative in the management of most patients with multivessel CAD requiring revascularization. A strategy using multiple repeated PTCA procedures when necessary results in prolonged infarct-free survival, with long-term freedom from angina and limited crossover to CABG. PMID- 8198028 TI - Late results of coronary angioplasty in patients with left ventricular ejection fractions < or = 40%. AB - Left ventricular (LV) function is the most important independent predictor of long-term survival in patients with coronary artery disease, and results of bypass surgery improving survival in the setting of depressed LV function are well documented. Data regarding long-term outcome in patients undergoing coronary angioplasty are limited. From 1983 through 1989, 343 consecutive patients with an ejection fraction (EF) < or = 40% (mean 34% +/- 5%) undergoing elective coronary angioplasty were evaluated, retrospectively. The mean age was 61 +/- 10 years and 80% were men. Angiographic success (469 of 496 narrowings) was 95%. Major complications occurred in 26 patients (7.6%): emergency bypass surgery (n = 11), nonfatal myocardial infarction (n = 8), and death (n = 9). Follow-up was available for 99% of patients with clinical success (mean = 36 +/- 22 months). Fourteen patients (4.5%) developed nonfatal myocardial infarction and 72 patients (23%) had symptomatic restenosis, 32 patients requiring repeat angioplasty or atherectomy and 29 bypass surgery. Fifty-six patients (18.2%) died. Three-year survival was 84%. EF was a significant predictor of death: 3-year survival was 69%, 83% and 92%, respectively, in patients with EF < or = 30%, 31% to 35%, and 36% to 40% (p = 0.0001). A high angiographic success rate and an acceptable procedural risk were encountered in patients with depressed LV function undergoing angioplasty. The 3-year mortality rate, however, is substantial and directly related to the degree of LV dysfunction. PMID- 8198029 TI - Intravascular ultrasound characterization of thrombi of different composition. AB - An in vitro model was designed to test the hypothesis that thrombi of varying composition have different echogenic patterns. Thrombi were prepared in specially designed tubes, mounted on a holder that allows introduction of an intravascular ultrasound catheter rotated inside a subselective sheath. The thrombi were made by the addition of thrombin to whole blood, platelet-rich plasma, and to mixtures of whole blood and platelet-rich plasma with increasing concentration of whole blood relative to the volume of the mixture in the following ratios: 1:5, 2:5, 3:5 and 4:5. Sixty-six thrombi prepared from 11 blood samples of healthy subjects were studied and compared with control tubes filled with saline solution. Platelet-rich thrombi showed low echogenicity similar to saline solution. Whole blood thrombi appeared uniformly "speckled." Mixtures of whole blood and platelet rich plasma showed a gradual increase in echogenicity with an increasing amount of whole blood in the mixture. Quantitative videodensitometry compared the gray scale intensity of each image relative to background saline. The mean value of echogenicity of platelet-rich thrombi was 0.9 +/- 1.2, and the mean value of whole blood thrombi was 13 +/- 5.3. Platelet-rich thrombi are echo-lucent, and the main echogenic reflectance of thrombi originates from red blood cells. The ultrasound intensity is in linear relation to the amount of red blood cells in the thrombus. PMID- 8198030 TI - Antithrombotic properties of transdermal nitroglycerin in stable angina pectoris. AB - Nitroglycerin provides an external source of nitric oxide which stimulates guanylate cyclase and produces vasodilatation and inhibition of platelet function. The antithrombotic effects of intravenous nitroglycerin were recently documented in various experimental models and in patients with unstable angina. This protocol was designed to evaluate whether these effects could also be detected with transdermal nitroglycerin in patients with stable angina. In a randomized, double-blind, controlled parallel trial, 22 patients received transdermal nitroglycerin, 0.6 mg/hour (11 patients), or placebo (11 patients). Platelet aggregation to adenosine diphosphate (ADP) and to thrombin was measured in whole blood. Thrombus formation was assessed on porcine aortic media exposed to the patient's venous blood for 3 minutes at shear rates of 2,546 and 754 s-1. Platelet aggregation to ADP decreased from 7.7 +/- 0.8 to 5.3 +/- 0.8 ohms (p < 0.05) with nitroglycerin, and to thrombin from 15.6 +/- 1.2 to 12 +/- 1.2 ohms (p < 0.05). Thrombus size at the high-shear rate decreased from 2.8 +/- 0.7 to 1.0 +/- 0.3 microns 2 (p < 0.05), and at the low-shear rate from 2.5 +/- 0.5 to 1.0 +/- 0.2 microns 2 (p < 0.05). Placebo had no significant effect on platelet aggregation and platelet thrombus deposition. These parameters were all reduced by > or = 20% in 8 patients taking nitroglycerin but only in 3 patients taking placebo (p < 0.05). Transdermal nitroglycerin significantly inhibits platelet aggregation and mural thrombus formation in patients with angina pectoris. PMID- 8198031 TI - Effects of bepridil on silent myocardial ischemia and eicosanoid metabolism in chronic stable angina pectoris after healing of myocardial infarction. AB - To investigate the effects of bepridil on silent myocardial ischemia and on eicosanoid metabolism, 10 patients with chronic stable angina underwent exercise treadmill testing and 48-hour ambulatory electrocardiographic monitoring both before and after 4 weeks of bepridil administration (150 mg/day). Fasting venous levels of thromboxane B2, 6-keto-prostaglandin F1 alpha, and leukotriene C4 were measured by radioimmunoassay. Bepridil decreased heart rate responses to daily activities during ambulatory monitoring, and significantly (p < 0.05) reduced the median frequency and duration of silent myocardial ischemic episodes (from 5.5 to 0 events/48 hours and from 86 to 0 minutes/48 hours respectively). Bepridil significantly decreased the blood pressure heart rate product at peak exercise and significantly prolonged the mean exercise tolerance time (from 456.6 to 527.0 second). Bepridil also significantly decreased the plasma levels of thromboxane B2 and leukotriene C4 at rest. These results suggest that bepridil may reduce silent myocardial ischemic episodes either by the reduction of cardiac oxygen demand during daily activities and exercise stress, or by controlling coronary and systemic vasomotor tone. The drug also has a salutary effect on eicosanoid metabolism, to which its efficacy on silent myocardial ischemic episodes may be related. PMID- 8198032 TI - Comparison of continuous ST-segment recovery analysis with methods using static electrocardiograms for noninvasive patency assessment during acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 7 Study Group. AB - Continuous ST-segment recovery analysis and 5 static methods using ST-segment comparison between a pre- and post-treatment electrocardiogram were compared for their ability to predict infarct-related artery patency in 82 patients with acute myocardial infarction who underwent angiography a median of 124 minutes after onset of thrombolytic treatment. Accuracy at the moment of angiography was 85% (95% confidence interval [CI] 77% to 93%) for the continuous method, and 68% (CI 57% to 78%), 78% (CI 69% to 87%), 83% (CI 74% to 91%), 82% (CI 73% to 90%), and 80% (CI 71% to 89%) for the static methods. At the moment of angiography the most accurate static method and the continuous method agreed in patency assessment in 90% of the patients (CI 84% to 97%). Agreement was reduced to 83% (CI 75% to 91%) of patients when a patency assessment was performed earlier at 90 minutes after treatment onset, and was only 77% (CI 68% to 86%), at 60 minutes. Early disagreement was mainly seen when the continuous ST recording showed ST recovery from a delayed peak ST elevation after the pretreatment static electrocardiogram or when dynamic ST changes suggesting cyclic reperfusion occurred. Continuous ST segment recovery analysis appears to be as accurate as the most accurate static methods. Continuously updated reference points appear to give important additional information when ST recovery follows a delayed peak ST elevation or when re-elevation occurs, suggesting cyclic flow changes. Such findings appear to affect about half of patients with acute myocardial infarction treated with intravenous thrombolysis, particularly early after administration of therapy. PMID- 8198033 TI - Comparison of defibrillator therapy and other therapeutic modalities for sustained ventricular tachycardia or ventricular fibrillation associated with coronary artery disease. AB - Outcomes of 282 patients referred to the arrhythmia service at Montefiore Medical Center for sustained ventricular tachycardia (n = 214) or ventricular fibrillation (n = 68) associated with coronary artery disease were analyzed retrospectively. All patients underwent serial drug trials by electrophysiologic testing and Holter monitoring. Sixty-eight patients who did not respond to drug therapy were treated with implantable cardioverter-defibrillators (ICD group), and 214 patients were treated with other methods guided by electrophysiologic testing and Holter monitoring (non-ICD group). The non-ICD group included 49 patients who responded to drug therapy as judged by electrophysiologic testing, as well as patients who did not respond and were not treated with defibrillator therapy for various reasons. Ten patients died in the hospital (2 patients in the ICD group, 8 in the non-ICD group). Actuarial survival rates free of total cardiac death at 1, 2, and 3 years were, respectively, 94%, 87%, and 85% in the ICD group, and 82%, 78%, and 73% in the non-ICD group (p = NS). Survival rates free of total death at 1, 2, and 3 years were 90%, 82%, and 76% in the ICD group, and 82%, 76%, and 70% in the non-ICD group, respectively (p = NS). Survival rates free of total cardiac and total deaths of 49 patients treated with an effective regimen determined by electrophysiologic testing were not significantly different from those of the ICD group. This retrospective study suggests that outcomes of patients treated with ICDs may not be dramatically different from those of patients treated with other methods guided primarily by electrophysiologic testing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198034 TI - In vivo mitral valve morphology and motion in mitral valve prolapse. AB - Mitral leaflet morphology in mitral valve prolapse (MVP) has been suggested to be prognostically important, but in vivo valvular morphology is incompletely described in patients with MVP or in normal subjects. Accordingly, the length of both mitral leaflets and their zone of apposition, the thickness of their rough and clear zones, diastolic and systolic mitral annular diameters, and indexes of abnormal leaflet motion were measured in the parasternal long-axis echocardiographic view in 100 patients with MVP and 100 age- and sex-matched normal subjects. In both groups posterior leaflet thickness was related to age, as were anterior leaflet thickness and posterior leaflet length in patients with MVP. Compared with normal subjects, MVP patients without mitral regurgitation had thickened leaflets, elongated anterior leaflets, and large annular diameters (p < 0.0001). Patients with severe regurgitation had thicker leaflets, longer posterior leaflet and annular dimensions, and more abnormal leaflet motion than MVP patients without regurgitation. Leaflet thicknesses of different zones were supranormal in 60% to 67% and in 49% to 59% of MVP patients with and without severe regurgitation, respectively. MVP patients with regurgitation also had higher prevalences of abnormal mitral annular diameter than those without regurgitation (67% vs 29%) and > 3 mm posterior leaflet billowing into the left atrium (60% vs 34%). Thus, mitral valve size and leaflet thickness are increased in MVP patients without as well as with clinically important mitral regurgitation. The usefulness of leaflet thickening as a marker of severe MVP is limited by its high prevalence in patients with clinically mild MVP. PMID- 8198035 TI - Clinical impact of transesophageal echocardiography in the diagnosis and management of infective endocarditis. AB - Transesophageal echocardiography (TEE) has assumed a prominent role in the diagnosis and management of infective endocarditis (IE). The impact of negative TEE findings on the management of patients suspected of having IE is not clear. To better understand how a negative TEE examination would influence patient management, the medical records of 93 consecutive patients undergoing TEE to evaluate for IE were examined. The influence of TEE was assessed based on changes in diagnosis, antibiotic therapy, or the need for surgical intervention during hospitalization. The negative predictive value of TEE was found to be 100% in native valves and 90% in prosthetic valves. The overall impact of negative TEE findings was significant in terms of final diagnosis and duration of antibiotic therapy (a negative TEE resulted in 60% reduction in antibiotic duration, p = 0.0001). These findings suggest that in patients with native heart valves, a negative TEE examination virtually excludes IE. In patients with prosthetic valves, a negative TEE significantly decreases the likelihood of IE but does not completely exclude the diagnosis; therefore, in this setting, a negative finding should be closely correlated with the clinical course. PMID- 8198036 TI - Effectiveness of enalapril in combination with low-dose hydrochlorothiazide versus enalapril alone for mild to moderate systemic hypertension in black patients. AB - The importance of concomitant low-dose hydrochlorothiazide was assessed in black hypertensive patients treated with enalapril. Left ventricular (LV) mass and function, metabolic parameters, 24-hour ambulatory blood pressure (BP), exercise duration, and systolic BP response were evaluated before and after drug therapy. Enalapril 20 mg (group 1) or enalapril 20 mg plus hydrochlorothiazide 12.5 mg (single tablet; group 2) was given to 38 patients for 9 weeks in a double-blind, placebo-controlled, randomized study. LV mass measured 61 +/- 17 versus 102 +/- 23 g/m2, and 24-hour ambulatory BP measured 120 +/- 8/75 +/- 6 versus 155 +/- 12/100 +/- 6 mm Hg in matched control subjects (n = 40) versus hypertensive patients, respectively. No clinically important changes occurred in total cholesterol, serum uric acid or potassium in either group. Enalapril slightly reduced 24-hour ambulatory BP from 154 +/- 15/100 +/- 7 mm Hg to 148 +/- 19/96 +/ 11 mm Hg after treatment (p < 0.05 for systolic BP); systolic BP load (70% to 59%, p < 0.05), and diastolic BP load (67% to 60%, p = NS) decreased. Baseline BP decreased from 157 +/- 9/101 +/- 6 to 132 +/- 13/86 +/- 8 mm Hg (p < 0.0001); systolic BP load (64% to 29%, p < 0.0001), and diastolic BP load (64% to 33%, p < 0.0001) decreased in group 2. Exercise systolic BP was attenuated (p = 0.007, group 2; p = NS, group 1) and duration increased (p = NS) only in group 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198037 TI - Surviving competitive athletics with hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy (HC) is probably the most common cause of sudden cardiac death in youthful athletes, and this diagnosis has represented a contraindication to continued participation in competitive sports. Less well appreciated is the fact that within the clinical spectrum of HC are patients who, despite having this disease, have been able to undertake particularly intensive and often extraordinary levels of training for sports competition over many years without dying suddenly. Fourteen such patients (13 men and 1 woman, aged 30 to 66 years [mean 43]) form the present study group. HC was initially identified at 24 to 57 years of age (mean 34), usually under fortuitous circumstances. Patients most often competed in distance running (including the marathon, 7), but also in swimming, triathalon, basketball, and football. The duration of training ranged from 6 to 22 years (mean 15) and 5 continue to train and compete actively. The magnitude of training, competition, and achievement was considerable in most patients; 12 of the 14 performed either at the national, collegiate or professional level in their sport, completed numerous marathon and triathalon events, or sustained particularly rigorous training regimens of > or = 50 miles/week. Echocardiographic studies demonstrated a left ventricular wall thickness of 18 to 28 mm (mean 20) in most patients (12 of 14) having a relatively localized pattern of ventricular septal hypertrophy. It is possible for some patients with HC to tolerate particularly intense athletic training and competition for many years, and even maintain high levels of achievement without incurring symptoms and disease progression or dying suddenly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198038 TI - Clinical and morphologic expression of hypertrophic cardiomyopathy in patients > or = 65 years of age. AB - Hypertrophic cardiomyopathy (HC) is most often identified in patients in the second through fifth decades of life, but has been increasingly recognized in older patients. The present report characterizes morphologic and clinical features of HC in 134 consecutively studied patients aged > or = 65 years referred to a tertiary center. Echocardiographic or clinical evaluation, or both, was performed in 134 patients aged 65 to 85 years (mean 72) at most recent evaluation. Selected findings were compared with those in 64 youthful patients with HC aged 15 to 35 years (mean 25). Most elderly patients (120 of 134, 90%) developed marked symptoms that usually became evident after age 55 years; 94 of 120 experienced sustained improvement with medical treatment or operation. Elderly patients had relatively mild left ventricular (LV) wall thickening (20 +/ 3 mm), generally confined to the septum. In most (i.e., 68%), septal hypertrophy was uniformly distributed with parallel right and left borders and associated with elliptical LV cavity shape; however, in 32%, an inhomogeneously hypertrophied septum bulged into the left ventricle, disrupting normal cavity shape. Dynamic subaortic obstruction was present under basal or provocable conditions in a particularly small LV outflow tract in 103 of 134 patients (77%), and was usually produced by relatively restricted excursion of the anteriorly displaced mitral leaflets and posterior septal motion. HC is characterized by age related differences in both clinical and morphologic expression. Elderly patients with HC characteristically demonstrate onset of cardiac symptoms late in life, as well as distinctive LV morphology and dynamics of outflow obstruction. PMID- 8198039 TI - Balloon aortic valvuloplasty in the young adult with congenital aortic stenosis. AB - Although balloon aortic valvuloplasty (BAV) is effective in the acute management of valvar aortic stenosis (AS), sustained benefit of this technique has been shown to vary in differing age groups. The role of BAV in the young adult with congenital, nondegenerative AS is poorly defined. The catheterization results and follow-up echocardiographic data were reviewed for all patients (n = 18) between the ages of 17 and 40 years (mean 23 +/- 7) undergoing BAV at our institution between March 1986 and January 1992. Peak-to-peak systolic ejection gradient was reduced by 55%, from 85 +/- 29 to 38 +/- 17 mm Hg (p < 0.001). Aortic valve area increased from 0.9 +/- 0.2 to 1.1 +/- 0.3 cm2 (p = 0.003). Results of dilation were inadequate in 2 patients. There were no deaths, myocardial infarction, or embolic events. The 16 "effectively" dilated patients were followed with serial echocardiography for a period of 1 to 82 months, demonstrating persistent gradient relief in most patients (maximal instantaneous gradient at follow-up, 55 +/- 17 vs 79 +/- 22 mm Hg before dilation, p < 0.001). Aortic valve replacements were performed in 5 patients, 2 with unsuccessful initial dilations. At the time of the most recent echocardiogram, 8 of 16 patients remained "incident free," with no subsequent catheterization or surgical interventions, a maximal instantaneous gradient of < or = 55 mm Hg, no more than moderate aortic regurgitation, and preserved ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198040 TI - Moderate- and high-intensity exercise lowers blood pressure in normotensive subjects 60 to 79 years of age. AB - To investigate the effects of exercise intensity on resting blood pressure (BP) in normotensive elderly subjects, 44 sedentary healthy subjects aged 60 to 79 years of age were studied during 6 months of walking exercise. Subjects were ranked according to maximal oxygen consumption and randomly stratified to groups that trained at 70% (n = 19) or 80% to 85% (n = 14) of maximal heart rate reserve, or to a control group (n = 11) that did not train. Initial BP was established during a 2- to 3-week control period. During the first 3 months, both exercise groups progressed to 70% of heart rate reserve for 40 minutes 3 times each week. The moderate-intensity group continued to train at 70% (45-minute duration) for an additional 3 months, whereas the high-intensity group progressed to training at 85% of heart rate reserve (35-minute duration). Maximal oxygen consumption increased (p < or = 0.05) during the initial 3 months in both exercise groups (25.2 to 28.1 ml.kg-1.min-1 and 26.3 to 29.3 ml.kg-1.min-1) and continued to increase (p < or = 0.05) after 3 additional months of training, but the increase was greater (p < or = 0.05) in the high-intensity group (28.1 to 29.4 ml.kg-1.min-1 and 29.3 to 32.8 ml.kg-1.min-1). Systolic BP decreased (p < or = 0.05) similarly at 6 months in both training groups (120 to 111 mm Hg and 120 to 112 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198041 TI - Failure of internal mammary artery grafts in patients with narrowing of the subclavian artery. PMID- 8198042 TI - Improved transesophageal echocardiographic assessment of significant proximal narrowing of the left anterior descending and left circumflex coronary arteries using echo contrast enhancement. PMID- 8198043 TI - Pravastatin, lipids, and major coronary events. PMID- 8198044 TI - Assessment of left atrial volumes and phasic function using cine magnetic resonance imaging in normal subjects. PMID- 8198045 TI - Prostacyclin synthesis in heart transplant recipients. PMID- 8198046 TI - The top 10 reasons cardiologists and other physicians are not interested in lipids. PMID- 8198047 TI - Reestablishment of a section on international nutrition in the AJCN. PMID- 8198048 TI - Determinants of diet glycemic index calculated retrospectively from diet records of 342 individuals with non-insulin-dependent diabetes mellitus. AB - Controlled trials have shown that a diet with a low glycemic index improves blood glucose and lipid control in patients with diabetes. To study the distribution and determinants of diet glycemic index, we obtained two 3-d diet records from 342 free-living subjects with non-insulin-dependent diabetes. Mean +/- SD 24-h intakes were as follows: energy, 7170 +/- 1890 kJ; fat, 33.6 +/- 6.5% of energy; protein, 20.1 +/- 3.2% of energy; available carbohydrate, 45.3 +/- 7.2% of energy; and dietary fiber, 17.2 +/- 6.4 g. Diet glycemic index values (85.4 +/- 4.55, range, 70-97.8) were normally distributed. Diet glycemic index was inversely associated with intake of simple sugars, whether expressed in grams (r = -0.426), percent of energy (r = -0.446), or percent of carbohydrate (r = 0.453, P < 0.001). By step-wise-multiple-linear regression, grams carbohydrate and percent protein were also independently related to diet glycemic index. Differences in diet glycemic index between men and women, and between subjects on different types of diabetes therapy were explained by differences in intake of simple sugars. PMID- 8198049 TI - Efficacy of water-soluble vitamin E in the treatment of vitamin E malabsorption in short-bowel syndrome. AB - A water-soluble form of vitamin E, tocopheryl succinate polyethylene glycol 1000 (TPGS), was used as an oral vitamin E supplement in a 71-y-old patient with severe fat malabsorption and vitamin E deficiency secondary to short-bowel syndrome. An absorption test with deuterium-labeled TPGS demonstrated that TPGS was absorbed and the released alpha-tocopherol was transported normally in lipoproteins. The disappearance portion of the deuterated alpha-tocopherol curves were parallel to those in control subjects, suggesting normal metabolic turnover of alpha-tocopherol. Long-term (3 y) supplementation with orally administered TPGS (10,360 mg or 4000 IU/d) maintained normal plasma alpha-tocopherol concentrations, raised adipose tissue alpha-tocopherol concentrations, and prevented further progression of the neurological abnormalities resulting from vitamin E deficiency. Thus, TPGS can be an effective vitamin E supplement in short-bowel syndrome despite severe fat malabsorption. PMID- 8198050 TI - American health care reform: implications for medical nutrition therapy. PMID- 8198051 TI - Sex differences in lean and adipose tissue distribution by magnetic resonance imaging: anthropometric relationships. AB - This study compared total and regional adipose tissue (AT) and lean tissue (LT) distribution measured by magnetic resonance imaging (MRI) in obese, android women (n = 40) and mean (n = 17). Women had significantly (P < 0.01) greater subcutaneous AT (39.6 +/- 11.6 vs 30.7 +/- 7.5 L) but significantly (P < 0.01) less visceral AT (2.5 +/- 1.1 vs 4.8 +/- 2.1 L) and LT (42.8 +/- 4.7 vs 58.2 +/- 6.2 L) compared with men. Segmentation of the visceral AT volume demonstrated that women had significantly (P < 0.01) less intraperitoneal (1.98 +/- 0.84 vs 3.74 +/- 1.61 L) and extraperitoneal AT (0.51 +/- 0.23 vs 1.04 +/- 0.47 L). When the legs, hip and pelvic region, and abdomen and torso regions were compared, women had significantly greater absolute quantities of subcutaneous AT and significantly less LT in all regions (P < 0.01); however, in all regions the relative distribution of both was similar. Anthropometric prediction of MRI measured total AT gave SEs of 7.7% for women and 7.5% for men, for visceral AT 30% for women and 19% for men. Anthropometric prediction of LT gave SEs of 6.5% for women and 3.6% for men. PMID- 8198052 TI - Correlates of over- and underreporting of energy intake in healthy older men and women. AB - The aim of this study was to determine whether variations in physiological characteristics were predictive of over- or underreporting of energy intake in older men and women. Total energy expenditure was predicted in 81 older men (66 +/- 6 y) and 56 older women (66 +/- 6 y) from a previously developed equation that uses the doubly labeled water method. The degree of over- or underreporting of energy intake was derived by subtracting predicted total daily energy expenditure from self-reported energy intake obtained from a 3-d diet record. Older women underreported energy intake (-2206 kJ/d +/- 1841) to a greater degree than did older men (-1301 kJ/d +/- 1908) (P < or = 0.01). In men, none of the physiological variables were significantly correlated with over- or underreporting of energy intake. Among the women, percent body fat was negatively correlated with underreporting of energy intake (r = -0.42, P = 0.001). Thus, the underreporting of energy intake increased with the amount of adiposity in women. PMID- 8198053 TI - Pharmacological doses of vitamin E and insulin action in elderly subjects. AB - Twenty elderly (77 +/- 0.4 y), nonobese [body mass index (in kg/m2) 26.4 +/- 0.5] subjects with normal glucose tolerance were submitted to a euglycemic hyperinsulinemic (3.5 pmol.min/kg) glucose clamp in a double-blind, crossover, randomized procedure after 4 mo treatment with either vitamin E (900 mg d-alpha tocopherol/d, Ephynal; Roche, Milan, Italy) or placebo. Body mass index was practically unchanged throughout the study. After the glucose clamp, insulin mediated stimulation 2 of whole-body glucose disposal (18.4 +/- 0.5 vs 26.1 +/- 0.6 mumol.min/kg lean body mass P < 0.02) was significantly potentiated by vitamin E rather than placebo administration. Furthermore, net changes in plasma vitamin E concentrations correlated with net changes in insulin-stimulated whole body glucose disposal (r = 0.60 P < 0.003). Plasma vitamin E concentrations seem to play an important role in the modulation of insulin action in elderly people. PMID- 8198054 TI - Reference ranges for erythrocyte pyridoxal 5'-phosphate concentration and the erythrocyte aspartate transaminase stimulation test in lactating mothers and their infants. AB - We determined reference ranges for erythrocyte pyridoxal 5'-phosphate concentrations (EPLP) and erythrocyte aspartate transaminase basal activities (EASTo) and activation coefficients (alpha EAST) in lactating mothers and infants from data of mothers receiving a vitamin B-6 supplement and infants breast-fed by mothers with adequate vitamin B6 status. The mothers' vitamin B6 status was assessed on the third day postpartum (pp) (n = 91) and at 2 mo (n = 114), 4 mo (n = 117), 6 mo (n = 110), and 9 mo (n = 40) pp and that of the exclusively breast fed infants at 2 mo (n = 90), 4 mo (n = 106), and 6 mo (n = 99). We also examined 9-mo-old infants (n = 39) who, besides breast milk, had received solids after 6 mo, and 12-mo-old infants (n = 100) who had received solids beginning at 4-6 mo and dairy products at 9 mo. Values indicating deficiency for at least two of the three indexes distinguished the 5-10% of mothers and infants with the lowest vitamin B6 status. The reference ranges for EPLP, EASTo, and alpha EAST for infants and for mothers during the first months of lactation differ from those reported earlier for adults. PMID- 8198055 TI - Effects of two high-fat diets with different fatty acid compositions on glucose and lipid metabolism in healthy young women. AB - Effects of two experimental diets with a relatively high fat content--one enriched with saturated fatty acids (SAFA-diet) and the other with a low content of erucic acid rapeseed oil and rich in monounsaturated fatty acids (MUFA-diet)- on glucose and lipid metabolism were examined in healthy young women. The study was carried out with a randomized, crossover study design with each diet lasting 3 wk and a 2-wk washout period between the experimental diets. Glucose area under the curve during the intravenous glucose tolerance test (glucose dose 300 mg/kg, plasma samples before glucose dose and at 10-min intervals for 90 min) was significantly lower and the glucose disappearance rate after a glucose injection tended to be steeper after the MUFA-diet than after the SAFA-diet. After the MUFA diet serum total cholesterol was 21.6% lower and serum low-density-lipoprotein cholesterol 29.5% lower than after the SAFA-diet, but high-density-lipoprotein cholesterol did not differ between the diets. The results give suggestive evidence that the dietary fatty acid composition affects glucose tolerance of healthy subjects. PMID- 8198056 TI - Plasma and tissue lipids of piglets fed formula containing saturated fatty acids from medium-chain triglycerides with or without fish oil. AB - Addition of fish oil (FO) with carbon chain 20 and 22 (long-chain polyunsaturated fatty acids; LCPs) n-3 fatty acids to formula has been considered as a method to provide 22:6n-3 to preterm infants. These studies determined the effects of including 0.73% n-3 LCPs from FO in formula containing saturated fatty acids as medium-chain triglyceride (MCT) oil on plasma and organ triglyceride (TG), phospholipid (PL), and cholesterol ester (CE) contents and compositions in piglets. Reference piglets were fed their own mother's milk. Piglets fed the formula with FO had significantly lower liver and kidney, but not plasma, TG concentrations; lower liver PL 20:4n-6; and higher plasma, liver, and kidney TG, PL, and CEn-3 LCPs than piglets fed the formula without FO. The increase in liver and kidney lipid n-3 LCPs and the decrease in kidney lipid content shows that inclusion of FO in formula with a high content of MCTs and 18:2n-6 does not promote tissue lipid metabolism similar to natural milk feeding. Piglets fed formula with FO had similar brain 20:4n-6 and 20:5n-3 but higher 22:6n-3 than did piglets fed sow milk. Diet-related differences in plasma and red blood cell PL were not reliable predictors of differences in brain LCP. PMID- 8198057 TI - Absorption, metabolism, and serum concentrations of cholesterol in vegetarians: effects of cholesterol feeding. AB - Serum concentrations and metabolism of cholesterol were studied in vegetarians basally and during a dietary cholesterol load. Cholesterol absorption efficiency was normal and synthesis was slightly enhanced, even though serum cholesterol precursors were not increased. The serum concentrations of total and low-density lipoprotein cholesterol were decreased proportionally to the reduced intake and absolute absorption of cholesterol. Fecal plant sterols were negatively correlated with the absorption efficiency of cholesterol and positively with fecal sterols and cholesterol synthesis, suggesting interference of high plant sterol intakes with cholesterol absorption. Cholesterol saturation and bile acid composition of the bile were not changed. The increased serum plant sterol cholesterol ratios were positively related to the intake and negatively to the biliary secretion of plant sterols. Cholesterol feeding increased absolute cholesterol absorption and serum concentrations of total and low-density lipoprotein cholesterol, did not change absorption efficiency or synthesis of cholesterol, but increased fecal cholestanol excretion. PMID- 8198058 TI - Contribution of odd-chain fatty acid oxidation to propionate production in disorders of propionate metabolism. AB - Whole-body propionate and protein kinetics and energy substrate metabolism were studied in five metronidazole-treated patients with propionic or methylmalonic acidemias by the use of a primed, 4-h constant infusion of [1-13C]propionate and L-[O-2H5]phenylalanine combined with indirect calorimetry. Measurements were performed during fasting and carbohydrate feeding, successively, to assess the contribution of odd-chain fatty acid oxidation to total propionate production. Fat oxidation decreased from 490 +/- 179 to 57 +/- 49 mumol.kg-1.h-1 (P < 0.05) as a result of feeding. Propionate appearance rate was 38.6 +/- 8 mumol.kg-1.h-1 during fasting and decreased to 22.6 +/- 5 mumol.kg-1.h-1 (P < 0.05) on the carbohydrate diet. Precursor amino acid catabolism did not change significantly (22 +/- 5 vs 21.2 +/- 5 mumol.kg-1.h-1), suggesting that the 41% reduction in propionate production observed in response to feeding was related to the suppression of fatty acid oxidation. Therefore, significant therapeutic gains may be expected from the use of diets aimed at reducing lipid oxidation. PMID- 8198059 TI - Source and amount of dietary nonspecific nitrogen in relation to whole-body leucine, phenylalanine, and tyrosine kinetics in young men. AB - We studied the effects of amount and source of nonspecific nitrogen (NSN) on the oxidation of leucine and hydroxylation of phenylalanine. In phase 1, seven adult males received for 6 d diets providing indispensable amino acid intakes to meet the 1985 FAO/WHO/UNU (FAO) requirements or our proposed requirement values (MIT). During one diet period with each diet, the NSN of the basal diets (total nitrogen intake: 107 mg N.kg-1.d-1) was increased to a total of 160 mg N.kg-1.d-1. On the morning of day 7, an 8-h constant intravenous tracer-infusion protocol (3-h fast; 5-h fed state) was conducted with L-[1-13C]leucine, L-[ring-2H5]phenylalanine, and L-[3,3,2H2]-tyrosine as tracers. In phase 2, six subjects were given three diets for 6 d, supplying 107 mg N.kg-1.d-1; NSN was a mixture of dispensable amino acids in which glutamine accounted for 0%, 12.5%, and 100% of total NSN. Leucine oxidation and phenylalanine hydroxylation rates and whole-body leucine and phenylalanine balances were unaffected by addition of supplemental NSN to the diets in phase 1 or by amino acid source of NSN in phase 2. Leucine and phenylalanine balances were lower (P < 0.05) for FAO compared with MIT diets. PMID- 8198060 TI - Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein. AB - The object of this study was to determine whether it is possible to reliably estimate the renal net acid excretion (NAE) produced by adults consuming different amounts of dietary protein. A physiologically based calculation model that corrects for intestinal absorption of minerals and sulfur-containing protein and assumes a rate of urinary excretion of organic acids proportional to body surface area was used to estimate NAE. Urinary excretion of different minerals and NAE was measured during the last 48 h of each of four separate 5-d diet periods in six healthy adults. On the basis of food tables, the four nearly isoenergetic diets (one lacto-vegetarian and one high- and two moderate-protein diets) were estimated to yield the following NAE values: 3.7, 117.5, 62.2, and 102.2 mEq/d, respectively. The analytically determined urinary NAE (24.1 +/- 10.7, 135.5 +/- 16.4, 69.7 +/- 21.4, and 112.6 +/- 10.9 mEq/d) corresponded reasonably well to these estimates, suggesting that the calculation model is appropriate to predict the renal NAE from nutrient intake and anthropometric data. PMID- 8198061 TI - Gastrointestinal effects and energy value of polydextrose in healthy nonobese men. AB - We studied seven healthy volunteers before and during acute (PD1) and chronic (PD2) ingestion of 30 g polydextrose (PD)/d. The energy value of PD was assessed after [U-14C]PD was added to the 10-g morning dose of PD during PD1 and at the end of PD2. Thirty-one +/- five percent (mean +/- SD) (PD1) and 29 +/- 4% (PD2) of the dose appeared in breath within 48 h. A small fraction of the ingested radioactivity was recovered in urine (4 +/- 1%) and excreted in flatus (< or = 1%) and in feces as volatile fatty acids (VFAs) (< 1%) and bacteria (3-4%); the remaining radioactivity in stools, 33 +/- 3% (PD1) and 32 +/- 4% (PD2), was assumed to be intact PD. Breath excretion of the label was 49 +/- 5% after intracolonic infusion of [U-14C] acetate. The energy value of PD, calculated by means of Miller and Wolin's stoichiometric equation of colonic fermentation, was similar during PD1 and PD2: 4.0 and 6.1 kJ/g, respectively, when breath 14CO2 and VFA production from PD were used for calculation. PMID- 8198062 TI - Plasma response of children to short-term chronic beta-carotene supplementation. AB - Plasma concentrations of beta-carotene and retinol after supplementation of children with beta-carotene in supplements and in foods were compared in Guatemalan children. The children received 6 mg/d beta-carotene [1000 retinol equivalents (RE)] as purified supplements or as carrots for 20 d and the effects on plasma beta-carotene and retinol concentrations were assessed. Plasma concentrations of beta-carotene were increased by 0.59 +/- 0.65 and 0.60 +/- 0.67 mumol/L after supplementation with beta-carotene capsules for 10 and 20 d, respectively. Addition of cooked carrots to the diet resulted in no significant change in plasma beta-carotene. Fasting plasma retinol concentrations were 1.23 +/- 0.35 mumol/L and were not significantly changed in response to supplementation with either of the carotene treatments with retinyl palmitate (1000 RE/d) for 20 d. Possible explanations for the differences in effects of plasma concentrations between the two methods of supplementation are discussed. PMID- 8198063 TI - Evidence that iron stores regulate iron absorption--a setpoint theory. AB - To evaluate the concept of a predetermined "setpoint" for iron stores, 20 healthy elderly individuals (12 blood donors and 8 nondonors) were studied to examine the effects of changes in iron stores on iron absorption. Oral iron-absorption tests revealed a statistically significant increase (P < 0.001) in iron absorption in donors, 7.4 +/- 3.6% (mean +/- SD) compared with 2.5 +/- 1.4% in nondonors. In a comparison of percent iron absorption with changes in baseline iron stores, a statistically significant correlation was noted (r2 = 0.702, P < 0.001). Thus, reductions in iron stores were correlated with increases in iron absorption. Basal gastric acid output was found to be within normal limits (1.62-10.20 mmol/h) in all elderly subjects and unrelated to iron stores. These findings are consistent with iron absorption being regulated according to the degree of depletion of iron stores from predonation values and is consistent with a proposed setpoint theory of iron stores. PMID- 8198064 TI - Effect of ascorbic acid on apparent iron absorption by women with low iron stores. AB - The effect of ascorbic acid supplementation on apparent iron absorption was tested in women with low iron stores. For 10 wk, 25 healthy nonpregnant women, aged 20-45 y with low serum ferritin (3.5-17.7 micrograms/L), consumed either a diet with predicted poorly bioavailable iron or a typical Western diet, classified according to dietary meat and ascorbic acid contents. Meals were supplemented with ascorbic acid (500 mg, three times a day) for 5 of the 10 wk, in a double-blind, crossover design. Ascorbic acid did not affect most biochemical indexes of iron status, the biological half-life of 59Fe, or apparent iron absorption (diet-feces) from either diet, but slightly increased serum ferritin (11.9 vs 10.7 micrograms/L, P < 0.06) when data from both diets were combined. These results support other evidence that ascorbic acid has less effect on iron bioavailability than has been predicted from tests with single meals. PMID- 8198065 TI - Decreased postprandial thermogenesis and fat oxidation but increased fullness after a high-fiber meal compared with a low-fiber meal. AB - The effect of a high-fiber (4.7 g/MJ) and an isoenergetic low-fiber (1.7 g/MJ) meal on 6-h postprandial thermogenesis, substrate metabolism, hormones, and satiety was investigated in 10 healthy, normal-weight male subjects. Diet-induced thermogenesis (DIT) was significantly reduced after the high-fiber meal (416.4 +/ 28.6 kJ/6 h) compared with the low-fiber meal (498.5 +/- 23.1 kJ/6 h; ANOVA: P < 0.0001), as was postprandial fat oxidation (P < 0.0001). The difference in DIT was correlated with the different palatability of the test meal (r = 0.89, P < 0.01). No differences were observed in plasma concentrations of glucose, insulin, norepinephrine, epinephrine, or gastrointestinal hormones, but C-peptide increased less (P < 0.05) and nonesterified fatty acids decreased more (P < 0.05) after the high-fiber meal. Finally, fullness was increased and desire to eat decreased after the high-fiber meal (P < 0.0001). In conclusion, a high-fiber meal decreased DIT and fat oxidation but increased fullness compared with a low fiber meal. PMID- 8198066 TI - Glutamine metabolism in healthy adult men: response to enteral and intravenous feeding. AB - To assess the effect of feeding on glutamine kinetics, six healthy men received 4 h intravenous infusions of L-[2-15N]glutamine and L-[1-13C]leucine on 3 separate days: 1) in the postabsorptive state, 2) over the course of an 8-h nasogastric infusion of a small peptide-based nutrient mixture, and 3) during an 8-h isonitrogenous, isoenergetic intravenous infusion (1.5 g amino acid.kg-1.d-1; 130 kJ.kg-1.d-1, or 31 kcal.kg-1.d-1; 58% carbohydrate and 42% fat). Regardless of the route, nutrition increased leucine appearance rate (Ra) and oxidation, stimulated protein synthesis, and improved leucine balance; apparent rates of protein breakdown decreased during enteral nutrition only. Glutamine Ra increased 16.8% (NS) and 26.2% (P < 0.01) with parenteral and enteral feeding, respectively, over postabsorptive values. The present findings are consistent with a major role of glutamine in interorgan nitrogen transport in the fed state and further suggest that increased availability of precursors may stimulate glutamine synthesis de novo, and enteral infusion of peptide-bound amino acids may be an effective route to provide free glutamine to the rest of the body. PMID- 8198067 TI - Insulin-like growth factor-I (IGF-I) responses in rats maintained with intravenous or intragastric infusion of total parenteral nutrition solutions containing medium- or long-chain triglyceride emulsions. AB - Our objective was to determine how intravenous or intragastric feeding affects serum concentrations of insulin-like growth factor (IGF)-I and -II and IGF binding proteins (IGFBP), and hepatic abundance of IGF-I mRNA. Male Fischer 344 rats (235-246 g) were fed for 14 d by intravenous or intragastric infusion with total parenteral nutrition (TPN) solutions providing 65% of energy from long chain triglyceride (LCT) or a 3:1 admixture of medium-chain triglyceride (MCT) and LCT emulsions (MCT/LCT). Twice as much TPN solution was required per gram of weight gain with MCT/LCT compared with LCT infusion (P < 0.0003). Serum IGF-I and -II concentrations and hepatic IGF-I mRNA abundance were not significantly different. Circulating concentrations of IGFBPs with molecular weights of 38,000 43,000 (IGFBP-3) were significantly greater with intravenous MCT/LCT than with intravenous LCT infusion. Our data demonstrate that reduced growth in rats given TPN containing MCT/LCT compared with LCT emulsions is not associated with reduced serum IGF-I concentrations or hepatic abundance of IGF-I mRNA, although serum IGFBPs are elevated. PMID- 8198068 TI - Predictors of infant birth weight in gestational diabetes. AB - The objectives were to characterize and determine the predictors of birth weight among women with gestational diabetes mellitus (GDM), and to establish whether these predictors vary by prepregnancy body mass index (BMI). A cohort of 353 women with GDM was examined by using data from clinic charts and the McGill Obstetrical and Neonatal Database. Dietary treatment decreased the rate of weight gain (from 0.35 to 0.16 kg/wk, P < 0.0001) and fasting serum glucose (from 4.8 to 4.2 mmol/L, P < 0.001). Positive predictors of infant birth weight among the underweight and normal-weight women (BMI < or = 26) included prepregnancy BMI, height, parity, prediagnostic rate of weight gain, postprandial serum glucose, and gestational duration. Among the overweight and obese women (BMI > 26) the only variables that predicted increased birth weight were prediagnostic rate of weight gain, and fasting or postprandial serum glucose. Hence, prepregnancy body mass index exerts a strong effect on predictors of infant birth weight in GDM, indicating the need to consider prepregnancy weight in the treatment approach. PMID- 8198069 TI - A critical appraisal of goiter assessment and the ratio of urinary iodine to creatinine for evaluating iodine status. AB - Iodine status can be evaluated by goiter assessment and measurement of urinary iodine concentration in either 24-h urine collections or in casual samples. It is often impossible to make 24-h collections. Therefore, iodine concentration in casual samples is often expressed in terms of urinary creatinine, assuming creatinine excretion to be constant between and within individuals. In this study large inter- and intraindividual variations were observed in the creatinine content of casual samples ranging from 0.6 to 9.87 mmol/L. Further, the urinary iodine-creatinine ratio correlated significantly with the creatinine concentration; Spearman's rank-order correlation coefficient, rs = 0.39 (P < 0.001). If creatinine is a suitable index to correct for variations in iodine excretion, no correlation would be expected. We conclude that the iodine creatinine ratio in casual urine samples is an unsuitable indicator for evaluating iodine status in areas where large inter- and intraindividual variations in urinary creatinine excretion exist. PMID- 8198070 TI - Can linoleic acid contribute to coronary artery disease? PMID- 8198071 TI - Premenstrual syndrome does exist. PMID- 8198073 TI - Comment on OMA legal article. PMID- 8198072 TI - Harry L. Dougherty, 1994 Albert H. Ketcham Memorial awardee. PMID- 8198074 TI - Three-year orthodontic postgraduate education: desirability and feasibility. PMID- 8198075 TI - A comment on the association between cervical inclination and craniofacial structures. PMID- 8198076 TI - Role of protraction headgear in correction of a skeletal midface deficiency in a unilateral cleft lip and palate--an interim case report. PMID- 8198077 TI - Synthetic elastomeric chains: a literature review. PMID- 8198078 TI - The effects of load misalignment on tensile load testing of direct bonded orthodontic brackets--a finite element model. AB - A finite element model (FEM) of an orthodontic bracket bonded to enamel with glass ionomer cement was developed. The loading on the model simulated tensile loading conditions associated with the testing of bonding system strength. The primary purpose of this project was to ascertain the effects of load misalignment on the calculated stresses within the cement layer. The results indicate that peak stress values increase as the load deflection angulation increases. If the tensile load is inadvertently applied entirely on one wing of the bracket, the stress components nearly double in magnitude. PMID- 8198079 TI - Comparative evaluation of ceramic bracket base designs. AB - Since the initial introduction of ceramic brackets, base designs have been modified to reduce tooth damage during debonding. The purpose of this study was to compare shear and tensile bond strengths and fracture sites of four second generation ceramic brackets: Allure IV (A) (GAC International, Inc., Central Islip, N.Y.), Ceramaflex (C) (TP Orthodontics, Inc., LaPorte, Ind.), Intrigue (I) (Lancer Orthodontics, Carlsbad, Calif.), Transcend 2000 (T) (Unitek Corp., Monrovia, Calif.), and a foil-mesh base stainless steel bracket, DynaBond II (D) (Unitek Corp., Monrovia, Calif.). Twenty brackets of each type were bonded to 100 mandibular bovine incisor teeth with Concise bonding adhesive. The samples were thermocycled for 24 hours and the brackets were debonded with an Instron universal testing machine (Instron Corp., Canton, Mass.). A modified Transcend debonding instrument was used for tensile debonding, whereas a chisel was used for shear debonding. An analysis of variance was performed with a 0.05 level of confidence. Mean shear strengths (kg/cm2) necessary to debond were 174.0 (A), 71.0 (C), 189.0 (I), 228.0 (T), and 160.0 (D). Mean tensile strengths (kg/cm2) were 27.0 (A), 26.7 (C), 51.3 (I), 56.5 (T), and 48.6 (D). Fracture sites examined with a light microscope showed no enamel damage with any of the ceramic brackets. Intrigue was the only bracket to fracture and had 30% bracket fracture in the tensile mode and 20% bracket fracture in the shear mode. The percentage of fractures at the adhesive-bracket base interface for shear and tensile modes, respectively, were 80, 100 (A); 100, 90 (C); 10, 60 (I); 60, 90 (T); and 90, 80 (D).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198080 TI - The effects of the Frankel's function regulator on the Class III malocclusion. AB - The material of this investigation consisted of 40 functional Class III malocclusion subjects. Each treatment and control group consisted of 20 Class III cases (10 boys and 10 girls). The mean age of the subjects in the function regulator, FR-3, group was 9.5 years at the beginning of the treatment, and in the control group 9.3 years at the beginning of the observation period. The mean treatment period of the FR-3 group was 1.9 years and the mean observation period of the control group is 1.8 years. In this study, as a result of FR-3 appliance therapy in the functional Class III malocclusion group, the negative overjet that was present at the beginning of the treatment has been converted into a positive overjet by an average increase of 3.8 mm at the end of the treatment. The sum of downward and backward rotation of the mandible, the decrease in the SNB angle with a subsequent increase of the ANB angle, and the retrusion of the lower incisors were effective in the increase of the overjet. The increase in the SNA angle and the protrusion of the upper incisors were found to be insignificant. The overbite decreased due largely to the downward and backward rotation of the mandible. PMID- 8198081 TI - Biocompatibility of new, clinically used, and recycled orthodontic samarium cobalt magnets. AB - The aim of this study was to compare the cytotoxic effect of new, clinically used, and recycled samarium-cobalt magnets (SmCO5). Cytotoxicity was assessed by two in vitro methods, the millipore filter method and an extraction method. In the filter method, the test material and the target cells are separated by a thin, permeable membrane. The test assesses the cytotoxicity of both water soluble and nonwater soluble components of the test material. The extraction test, which has a higher sensitivity, assesses the cytotoxicity of water soluble components only. According to the filter method, one magnet (new) showed a mild cytotoxic effect; all other tested magnets showed no cytotoxicity. Judged by the extraction test, new as well as clinically used magnets demonstrated a weak cytotoxic effect, suggesting the presence of a small amount of leachable cytotoxic components. The level of exerted cytotoxicity of such components was significantly lower for clinically used than for new magnets. When recycled magnets were tested, the cytotoxicity had significantly decreased, (p < 0.001), and the cytotoxicity could be considered negligible. The results thus revealed that SmCO5 magnets can be recycled with maintained good biocompatibility. Because a small amount of water soluble cytotoxic agents seem to leach out from new partially stainless steel-coated samarium-cobalt magnets, it is recommended that they be stored in water for 24 hours before clinical use, thereby conceivably decreasing the oral exposure of water soluble cytotoxic agents. PMID- 8198082 TI - Craniofacial structure related to inheritance pattern in amelogenesis imperfecta. AB - The aim of this study was to investigate the craniofacial structure in 66 children and adolescents, 34 girls and 32 boys, with known clinical manifestations and inheritance patterns for amelogenesis imperfecta (AI), and to compare the results with those obtained in a control group of age and sex matched persons with normal occlusion. The ages ranged from 6.8 to 21.2 years. Clinically, AI was divided into cases characterized by either hypoplasia or hypomineralization of the enamel. In a further subgrouping, eight clinical variants were diagnosed. Measurements of 12 angular and 15 linear, parameters on lateral cephalometric radiographs were included in comparisons between the AI and the control group. Compared with the control group, the AI group displayed statistically significant differences indicating a skeletal open bite. In the analysis of inheritance patterns and clinical manifestations, a skeletal open bite was associated with autosomal dominant (AD) and X-linked inheritance, and in the AD group with hypomineralization. When all cases except those with X-linked inheritance were pooled, deviations indicating a skeletal open bite were found in the subgroups "rough hypoplastic AI" and "hypomineralization AI." Since a skeletal open bite was found both with X-linked inheritance and in some of the subgroups connected with autosomal inheritance, the hypothesis of a pleiotropic gene effect as the cause of the simultaneous occurrence can be ruled out. The influence of modifying genes or environmental factors is suggested. PMID- 8198083 TI - The maxillary-mandibular planes angle (MM degrees) bisector: a new reference plane for anteroposterior measurement of the dental bases. AB - A new plane, geometrically derived from the dental base planes, has been tested as an occlusal plane substitute for the measurement of anteroposterior jaw relationships. It lies close to but at an angle and inferior to the traditional occlusal planes and is highly reproducible at all times. Lateral cephalograms of 36 young adults (25 men and 11 women) and 43 10- to 12-year-old children (24 girls and 19 boys) were selected and the Wits technique of anteroposterior measurement was used to compare A-B values measured to the new plane with those measured to the functional occlusal plane (FOP) and to the traditional or bisecting occlusal plane (BOP). Because of the downward cant of the bisector anteriorly, B is projected onto it ahead of A in normal occlusion and coincides with A in skeletal (2) malocclusion. Mean values for normal occlusion were found to be approximately -4 mm for the children (-4.2 mm girls and -4.0 mm boys) and 4.5 mm for the adults (-4 mm women and -4.7 mm men). PMID- 8198084 TI - The etiology of late lower arch crowding alternative to mesially directed forces: a review. AB - The causes of late crowding in the lower arch alternative to mesially directed forces are reviewed under the headings: late mandibular growth, skeletal structure and complex growth pattern, soft tissue maturation, periodontal forces, tooth structure, occlusal factors, and connective tissue changes. A multifactorial basis for late lower arch crowding seems likely. PMID- 8198085 TI - The Broadbent-Bolton Growth Study--past, present, and future. AB - A computerized database of 14 textual elements has been created to describe the 4309 subjects enrolled in the Broadbent-Bolton Growth Study. The database can be searched by using Boolean operators to select subsets of subjects matched on the 14 data elements. The structure of the database, along with representative tables and charts of the data, is presented to aid researchers contemplating use of the collection for scientific investigation. PMID- 8198086 TI - Vignette. Anders Lundstrom. PMID- 8198087 TI - Colon polyps and cancer in 1994. PMID- 8198088 TI - Antibiotics and endocarditis. PMID- 8198089 TI - Colonic polyps in an unselected population: prevalence, characteristics, and associations. AB - OBJECTIVES: To provide a proctosigmoidoscopic review of a very large set of unselected control subjects, providing an unbiased view of colonic polyps in the general population. METHODS: Sigmoidoscopic data from 406 sequentially recruited subjects were analyzed. Participation rates were over 85%, and subjects were thus free of the usual selection bias. RESULTS: Thirty-eight percent of screened individuals were found to have distal colonic polyps. Adenomas were found in 12%, and hyperplastic polyps were found in 30% of screened individuals. Adenomas were more prevalent in males and in older individuals. Hyperplastic prevalence did not differ significantly by gender or age. Synchronous adenomatous and hyperplastic polyps occurred in 3% of screened individuals, but these lesions were not associated. CONCLUSIONS: Distal colonic adenomatous and hyperplastic polyps are very common in the general population and are not associated. The high frequency of these polyps raises questions about the feasibility of biopsy for all polyps, and suggests that further study is needed to determine the appropriate indications for subsequent colonoscopy. PMID- 8198090 TI - Pre-endoscopic antibiotics for the prevention of bacterial endocarditis: do we use them appropriately? AB - OBJECTIVE: Because native valve bacterial endocarditis following endoscopic procedures is extremely rare, recent guidelines have discouraged indiscriminate use of pre-endoscopic antibiotics. The purpose of this study was to determine whether these guidelines have had an impact in prescribing antibiotic prophylaxis prior to endoscopic procedures. METHODS: All ambulatory endoscopic procedures carried out from January 1, 1992, through December 31, 1992, in a 412-bed community hospital in Northern Virginia were reviewed to identify cases receiving antibiotic prophylaxis. Inpatients, percutaneous gastrostomies, and ERCPs were not included, since many had received antibiotics for reasons other than endocarditis prophylaxis. We also surveyed a random sample of board certified gastroenterologists practicing at teaching hospitals in Northern Virginia and Washington, DC, to determine their practice patterns. We used the recent recommendations of the American Heart Association with minor modification as the "appropriate" guideline. RESULTS: Only 10% of physicians use antibiotic prophylaxis appropriately. Most physicians over-utilize antibiotics in a variety of settings that do not require such measures. Conversely, many physicians do not prescribe antibiotics for disorders which do require prophylaxis. CONCLUSION: Although "appropriate" guidelines for prophylactic antibiotics are available, and we have estimated the risk of acquiring native valve bacterial endocarditis following endoscopic procedures to be only 1 in 5-10 million procedures, the majority of physicians do not use prophylactic antibiotics appropriately. PMID- 8198091 TI - Are women with breast, endometrial, or ovarian cancer at increased risk for colorectal cancer? AB - OBJECTIVES: Evidence is accumulating supporting the use of screening for colorectal cancer. Patients at higher risk for colorectal cancer are more likely to benefit from screening. Women with breast, endometrial, or ovarian cancer are often classified as at high risk for subsequent colorectal cancer, and are urged to undergo screening, but the basis for this is uncertain. METHODS: We performed a meta-analysis of published data to assess the risk of colorectal cancer after these cancers. RESULTS: Based on 154,270 women and 779,251 person-yr of observation (PYO) after breast cancer, 37,266 women and 229,498 PYO after endometrial cancer, and 41,366 women and 126,688 PYO after ovarian cancer, the age-adjusted relative risk (95% CI) for colorectal cancer after breast cancer was 1.1 (1.07, 1.19), after endometrial cancer 1.4 (1.32, 1.55), and after ovarian cancer 1.6 (1.40, 1.80). CONCLUSIONS: 1) Women with a history of breast, endometrial, or ovarian cancer are at a statistically significant increased risk for subsequent colorectal cancer. 2) Women with a history of endometrial or ovarian cancer are at higher risk than are women with breast cancer, but ascertainment bias from heightened medical surveillance after the diagnosis of a gynecologic malignancy may contribute to this observed increase in risk. 3) The association between these cancers and colorectal cancer suggests common etiologic factors, either environmental or genetic, but the degree of increased risk is small. PMID- 8198092 TI - Periodicity of hospital admissions for inflammatory bowel disease. AB - OBJECTIVES: It has been speculated that exacerbations of inflammatory bowel disease are influenced by seasonal variations. METHODS: This hypothesis was tested in a large data base of the Health Care Financing Administration (HCFA), consisting of all hospitalized US Medicare beneficiaries from four consecutive years. RESULTS: The total of hospital admissions (for all diagnoses) was characterized by a marked seasonal variation occurring similarly in each consecutive year. It was high during winter and low during summer. Peak and trough of admission rate varied by 10%. In striking contrast to this general pattern, both Crohn's disease and ulcerative colitis showed an annual pattern of variability without any clear-cut seasonality. However, the time trends of both diseases showed a striking parallelism concerning their short-term changes (affecting 1-3 consecutive months) and long-term changes (affecting 4-8 consecutive months). The parallelism of the temporal changes affected different age and sex groups alike. CONCLUSIONS: The parallel monthly variations suggest that exacerbations in the activity of inflammatory bowel disease may be modulated by exogenous factors, and that Crohn's disease and ulcerative colitis may be influenced by identical modulators of disease activity. PMID- 8198093 TI - Sequelae after esophageal variceal ligation and sclerotherapy: a prospective randomized study. AB - OBJECTIVES: Esophageal variceal ligation is a new approach to the treatment of esophageal varices that does not result in transmural tissue injury and inflammation, and therefore might produce fewer sequelae and symptoms than sclerotherapy. We conducted a prospective, randomized comparison of sclerotherapy with ligation to study the relative short-term risks of these two procedures with respect to bacteremia, pulmonary and coagulation function, esophageal motility, and gastroesophageal reflux. METHODS: Patients with previously documented high grade esophageal varices were randomized to receive sclerotherapy or ligation. Blood was drawn for culture and coagulation profiles, and patients underwent pulmonary function tests, esophageal manometry, and intraesophageal pH monitoring before and after treatment. RESULTS: Six patients with Childs class B cirrhosis and one patient with pre-sinusoidal portal hypertension underwent 20 courses of therapy. Neither sclerotherapy nor ligation produced significant clinical changes in pulmonary or coagulation parameters, or bacteremia requiring treatment. The majority of ligation treatments were without worsening of motility or reflux scores, and none were associated with symptoms. Sclerotherapy was followed by significantly greater esophageal dysmotility and worsening reflux patterns. CONCLUSIONS: Patient acceptance of ligation was much greater than that for sclerotherapy. Our data define the advantages of ligation over sclerotherapy. PMID- 8198094 TI - Post-sclerotherapy bacterial peritonitis: a complication of sclerotherapy or of variceal bleeding? AB - To assess the risk of bacterial peritonitis following endoscopic variceal sclerotherapy (EVS), we recorded the incidence of this complication within 2 wk of the procedure in all patients (n = 216) undergoing 1092 sclerotherapy sessions in our hospital during a 5-yr period (1987-1992). The sclerotherapy sessions were separated in prophylactic EVS (without a previous bleeding, n = 172 sessions), elective EVS (following a previous variceal bleeding, n = 720), and emergency EVS (within 24 h of a variceal bleeding, n = 200). During the study period, 60 patients with spontaneous bacterial peritonitis were recorded. In 10 patients, peritonitis was diagnosed within 14 days after EVS. Six patients received emergency EVS and four elective EVS. In seven patients, Gram-negative aerobic and anaerobic microorganisms were cultured from the ascitic fluid, and in three patients cultures were negative; however, an elevated ascitic fluid polymorphonuclear cell count of > 0.5 x 10(9) cells/L was present. The mean period between EVS and the diagnosis of peritonitis was 3.5 days. On average, the patients had been febrile during 2.1 days before the diagnosis was established. None of the patients who had received prophylactic EVS developed peritonitis. The calculated risk to develop peritonitis following elective EVS was 0.5% (4/742 sessions) and following emergency EVS 3% (6/200 sessions) (p = 0.019, Fisher's exact test). Gram-negative gut-derived microorganisms were the most common pathogenic bacteria cultured from the ascites, which is different from the microbial flora causing bacteremia after EVS. This suggests that the risk for bacterial peritonitis is determined primarily by factors associated with bleeding, such as shock with increased bowel wall translocation of bacteria. These results indicate that standard antibiotic prophylaxis before EVS is not indicated, but could be considered in patients with liver cirrhosis and ascites receiving emergency EVS. PMID- 8198095 TI - Portal shunting in inferior mesenteric vein in cirrhosis: correlation with hemorrhage from esophageal varices. AB - OBJECTIVE: Certain patients with portal hypertension develop large esophageal varices, whereas others have small varices, or none. Our objective in this study was to determine whether this variability depends upon the amount of blood derived by peripheral portosystemic collaterals. METHODS: Esophagogastroscopy to determine presence and size of esophageal varices, and pre-rectal portal scintigraphy to assess portosystemic shunt index (PSI) in inferior mesenteric vein were performed in 45 cirrhotics and 17 patients with pre-cirrhotic liver disease. RESULTS: Patients with cirrhosis had higher PSI than normal controls (67 +/- 4 vs. 8 +/- 2%; p < 0.0001) and pre-cirrhotic patients (vs. 34 +/- 6%; p < 0.0001). Neither variceal size nor PSI was correlated with Child-Pugh classification or hepatic venous pressure gradient. PSI was not related to the presence of varices or their size. On the other hand, patients with variceal hemorrhage had elevated PSI, compared with non-bleeders (80 +/- 4% vs. 59 +/- 6%; p < 0.005). CONCLUSIONS: This study shows that portosystemic collaterals in the inferior mesenteric vein do not prevent the formation of large varices. Furthermore, the magnitude of blood flow through peripheral collaterals might reflect the risk of variceal hemorrhage. PMID- 8198096 TI - Endoscopic balloon dilation for ulcer-induced gastric outlet obstruction. AB - OBJECTIVE: To determine the safety and efficacy of endoscopic balloon dilation for ulcer-induced gastric outlet strictures. METHODS: Review of the cumulative experience from two institutions involving 30 patients who underwent endoscopic balloon dilation for peptic ulcer-induced gastric outlet obstruction. Follow-up was by standardized interview at a mean of 15 months (range 4-28 months). RESULTS: Symptoms occurred for an average of 6 months before dilation and included weight loss, epigastric pain, nausea, vomiting, early satiety, bloating, and anorexia. Gastric outlet strictures had a median diameter of 6 mm (range, 0 10 mm). Ten (33%) patients had active ulcers. Six-millimeter to 18-mm (median 15 mm) balloons were inflated a median of 2 times (range 1-4 times) for a median of 60 s (range 30-180 s). Fifty-one procedures (1.7/patient) were performed; 20 (67%) patients had one treatment and 10 (33%) had multiple treatments. Twenty four (80%) patients achieved sustained symptom relief, 17 of 20 having a single procedure and 7 of 10 required multiple sessions. Dilation failed in 4 (13%) patients with long duodenal strictures. Two (6.7%) patients dilated to 18 mm suffered perforation. Both recovered uneventfully after surgery. CONCLUSIONS: Endoscopic balloon dilation is safe and effective for most patients with ulcer induced gastric outlet obstruction. PMID- 8198097 TI - Milk tolerance in adults with ulcerative colitis. AB - OBJECTIVES: There has been concern in the literature and among physicians and patients that milk intolerance may contribute to disease activity in ulcerative colitis. We sought to define whether patients with ulcerative colitis have problems with milk tolerance. METHODS: 1) A questionnaire was administered to a group of gastroenterologists. 2) Consecutive unselected ulcerative colitis patients were administered a questionnaire regarding issues concerning their ingestion and tolerance of milk products. 3) Patients, and age- and ethnically matched controls, underwent lactose hydrogen breath testing at a 50-g dose, and if intolerant, returned for testing at a 12.5-g dose. RESULTS: Eighty percent of responding physicians stated that they recommend avoidance of milk products at some time to their patients. Thirteen of 29 (44%) ulcerative colitis patients were lactose intolerant compared with five of 14 (36%) controls (p = 0.57). Of 11 subjects returning for the 12.5-g test dose, only three (28%) were intolerant. Of 10 ulcerative colitis patients tested during a flare, only two (20%) were intolerant. Nineteen of 28 (66%) patients reduced or eliminated milk products from their diet, but only 10 (45%) of these patients were lactose intolerant. The discordance rate for predicting lactose tolerance status among patients was 35%. By logistic regression analysis, age (p = 0.04) and ethnicity (p = 0.006) were the only variables that were predictive of an abnormal lactose hydrogen breath test. CONCLUSIONS: There are common misperceptions among physicians and patients about lactose intolerance in ulcerative colitis. Lactose intolerance in patients with ulcerative colitis is dependent on their age and ethnicity and not any particular aspects of their disease. The proscription of milk products during flares of disease by many physicians is not supported by this study. PMID- 8198098 TI - Intestinal permeability in patients infected with the human immunodeficiency virus. AB - OBJECTIVE: The etiology of acquired immunodeficiency syndrome (AIDS) enteropathy is unknown. This condition has been associated with malabsorption and villous atrophy. Other disorders with similar findings, including celiac disease, are characterized by altered intestinal permeability. Our objective was to confirm (or reject) our hypothesis that processes that cause increased permeability may occur in patients with AIDS, and thus be a cause of idiopathic diarrhea. METHODS: A lactulose-mannitol differential intestinal permeability test was performed in healthy controls, asymptomatic human immunodeficiency virus (HIV)-positive patients, and AIDS patients with and without diarrhea. RESULTS: Asymptomatic HIV positive patients lactulose and mannitol recoveries were no different than healthy control patients. AIDS patients without diarrhea had lactulose recovery similar to healthy controls and decreased mannitol recoveries; their mean lactulose:mannitol ratio was no different from that of controls, and less than that of AIDS patients with diarrhea. AIDS patients with diarrhea had increased lactulose recovery and decreased mannitol recovery; their mean lactulose:mannitol ratio was significantly greater than the ratios in all the other groups. CONCLUSIONS: Patients with AIDS and diarrhea have altered intestinal permeability. The decreased absorption of mannitol suggests that the functional absorptive surface of the intestine decreases as HIV disease progresses. PMID- 8198099 TI - Enhanced mucosal interleukin-6 and -8 in Helicobacter pylori-positive dyspeptic patients. AB - OBJECTIVES: To determine the concentrations of interleukin-1 beta, interleukin-6, and interleukin-8 in tissue homogenates of mucosal biopsy specimens from Helicobacter pylori-positive and -negative patients. METHODS: In 43 consecutive patients who underwent upper gastrointestinal endoscopy, seven antral biopsies were taken; three specimens were used for cytokine determination and the remaining four biopsies were processed for H. pylori detection. Peripheral venous blood was collected and IgG to H. pylori was assayed by an ELISA technique. RESULTS: Twenty-nine of 43 patients (67%) were histologically positive for H. pylori; all had chronic gastritis. The mucosal levels of interleukin-6 and interleukin-8 were significantly higher in H. pylori-positive patients than in the negative patients (p < 0.001). A significantly higher percentage of interleukin-8 was found in patients colonized by H. pylori with active superficial chronic gastritis (85.7%), compared to quiescent superficial gastritis (12.5%) (p < 0.01), and the median and range were, respectively, 400 (0 1000) and 0 (0-200) pg/mg protein (p < 0.001). In patients with active superficial gastritis, a significant correlation between interleukin-6 and -8 was found (p 0.01). No difference was found regarding the mucosal levels of interleukin-1 beta according to the presence of H. pylori. CONCLUSIONS: These results suggest a possible pathogenetic role for interleukin-6 and interleukin-8 in H. pylori-associated gastritis. PMID- 8198100 TI - Decrease in ornithine decarboxylase activity after eradication of Helicobacter pylori. AB - OBJECTIVE: Our aim was to determine whether gastric mucosal ODC activity is altered after successful eradication of HP. Recent reports have suggested that Helicobacter pylori (HP) infection of the stomach is associated with the development of gastric cancer. Gastrointestinal cancers usually do not arise de novo; a series of mucosal changes leading to neoplastic transformation and degrees of dysplasia are believed to precede the development of cancer. These conditions are associated with increased cellular proliferation. Ornithine decarboxylase (ODC) activity is induced by factors that stimulate cellular proliferation, and has been shown to be elevated in gastrointestinal neoplasia, including gastric cancer. METHODS: Gastric antral and body biopsies were obtained from 17 HP-positive patients at endoscopy, for ODC activity and histology (including Warthin Starry stain) before and 4-6 wk after successful triple therapy. RESULTS: Patients included 12 males and five females, with a mean age of 55 yr (27-73 yr). Mean ODC activity (in pmol CO2/mg protein/h) was significantly decreased after eradication of HP, compared with pretreatment levels in antral (147 +/- 26 vs. 80 +/- 15) and body mucosa (76 +/- 21 vs. 20 +/- 5) (p < 0.05). CONCLUSION: Successful eradication of HP decreases mucosal proliferative activity, as reflected by decreased ODC activity. We speculate that by decreasing mucosal proliferative activity, HP eradication may help decrease the subsequent risk of gastric cancer. PMID- 8198101 TI - Gastric mucosal EGF and PDGF receptor expression with ulcer healing by ebrotidine. AB - OBJECTIVES: Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) play important roles in the process of mucosal repair and restitution, and their biological effects are mediated by receptors located on the target cell surfaces. The purpose of this study was to assess the effect of the antiulcer agent, ebrotidine, on the expression of EGF and PDGF receptors with chronic ulcer healing. METHODS: Chronic gastric ulcers were developed in the rat by acetic acid technique. The animal were divided into two groups and were treated twice daily for 14 consecutive days, either with ebrotidine at 100 mg/kg, or placebo. At different stages of treatment, the animals were sacrificed and used for the isolation and quantification of gastric mucosal EGF and PDGF receptors. RESULTS: The binding assays revealed that ulcer healing was accompanied by an increase in mucosal expression of both types of receptors. A 1.7-1.8-fold increase in PDGF and EGF receptors occurred by the 4th day after the development of ulcer and reached a maximum of 3-fold increase by the 14th day, when the ulcer was essentially healed. Treatment with ebrotidine caused accelerated ulcer healing (7 days) which was accompanied by a significant enhancement in receptor expression. Compared to the controls, a 1.5-fold increase in EGF and 1.7-fold increase in PDGF receptor expression occurred by the 7th day of ebrotidine treatment, and a 1.4- to 1.5-fold increase was still observed at the 14th day of treatment. CONCLUSIONS: The results suggest that ebrotidine is capable of enhancement of gastric mucosal proliferative activities associated with ulcer healing through the stimulation of EGF and PDGF receptor expression. PMID- 8198102 TI - Ultrasound-guided fine-needle biopsy of hepatocellular carcinoma: comparison between smear cytology and microhistology. AB - OBJECTIVES: The aims of this study were to evaluate the typing accuracy of smear cytology and microhistology and of their association in the diagnosis of hepatocellular carcinoma arising in liver cirrhosis, and to analyze the usefulness of smear cytology in the diagnosis of well-differentiated neoplasms. METHODS: One hundred sixty patients with hepatocellular carcinoma underwent an ultrasound-guided fine-needle biopsy, providing material for cytological and histological study. In 73 patients, a double biopsy with noncutting and cutting needles was performed (double-needle group), whereas in the remaining 87, a single biopsy with cutting needle was carried out (single-needle group). RESULTS: In the whole population examined, smear cytology, microhistology, and their association, provided the diagnosis of hepatocellular carcinoma in 128 (80%), 98 (61%), and 144 (90%) cases, respectively. The double-needle and the single-needle groups did not differ significantly as to typing accuracy. Smear cytology correctly diagnosed 54 of 64 neoplasms classified histologically as well differentiated. CONCLUSIONS: Our results show that both smear cytology and microhistology should be applied immediately, when diagnosing hepatocellular carcinoma arising in liver cirrhosis, and that smear cytology is effective in the diagnosis of well-differentiated neoplasms. PMID- 8198103 TI - Frequent occurrence of hepatocellular carcinoma in cirrhotic livers after surgical resection of atypical adenomatous hyperplasia (borderline hepatocellular lesion): a follow-up study. AB - OBJECTIVES: Adenomatous hyperplasia (AH) of the liver occurs in chronic advanced liver diseases, and has been suspected to be a precancerous lesions in human hepatocarcinogenesis. METHODS: In this study, the incidence of hepatocellular carcinoma (HCC) after surgical resection of AH was evaluated in 24 patients with cirrhosis and AH in the absence of HCC (mean follow-up period, 31.4 months; range, 12-77 months). AH were classified as ordinary AH lacking hepatocellular atypia (OAH), atypical AH with structural and cellular atypia insufficient for carcinoma (AAH), and atypical AH with focal malignancy containing areas of HCC (FM). RESULTS: HCC was noted in a few years (follow-up period range, 12-77 months; mean, 31.4 months) in all 3 patients whose resected nodules were classified as FM, in 4 (36%) of 11 with AAH resected nodules, and none of 10 with OAH resected nodules. The incidence of HCC in the patients with FM or AAH nodules was significantly higher than that in those with OAH nodules. CONCLUSIONS: These results suggest that our classification of AH is useful in the assessment of the risk of HCC in patients with cirrhosis and AH, and that those with AAH or FM resected nodules must be followed up more frequently than those with OAH nodules, because of their higher risk of HCC. The frequent occurrence of HCC after resection of FM or AAH nodules may imply that HCC is of multicentric origin. PMID- 8198104 TI - Enhancement of gallbladder emptying in gallstone patients after oral cholestyramine. AB - OBJECTIVE: To evaluate whether a low dose of oral cholestyramine improves gallbladder emptying in gallstone patients. METHODS: Gallbladder volumes were assessed by sonography in 36 patients with cholesterol gallstones and 18 healthy controls. On three different days subjects ingested: 1) test meal alone, 2) test meal plus cholestyramine (4 g), and 3) cholestyramine alone (4 g). RESULTS: Fasting gallbladder volume (mean +/- SE, 25.9 +/- 1.8 ml and 19.2 +/- 1.3 ml for patients and controls, respectively, p < 0.05) and postprandial gallbladder residual volume (48.7 +/- 3.9% and 21.6 +/- 2.8% of fasting volume in patients and controls, respectively, p < 0.001) were larger in patients than controls, indicating impaired gallbladder emptying. Gallstone patients were divided into 19 "contractors" and 17 "hypocontractors" (residual gallbladder volume smaller or greater than mean +/- 2 SD of controls). Compared with the test meal alone, the addition of cholestyramine induced a further decrease of residual volume in contractors (from 30.4 +/- 2.1% to 19.8 +/- 1.9%, p < 0.001), hypocontractors (from 69.3 +/- 3.9% to 56.7 +/- 7.4%, p < 0.05), and controls (from 21.6 +/- 2.8% to 5.0 +/- 1.0%, p < 0.0004). Two hours after test meal plus cholestyramine gallbladder volume was still markedly reduced in both patients and controls. Fasting gallbladder volume 24 h after test meal plus cholestyramine was decreased in patients and in controls. The ingestion of cholestyramine alone initiated gallbladder evacuation comparable to that of test meal in both contractors and hypocontractors. CONCLUSIONS: A low dose of cholestyramine in combination with test meal induces a considerable decrement of gallbladder volume compared with test meal alone in gallstone patients. Cholestyramine alone causes a decrease of gallbladder volume which is comparable to that observed in response to test meal alone. PMID- 8198105 TI - The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K. AB - BACKGROUND: Coagulopathy manifest by elevation of the prothrombin time (PT) in patients receiving broad spectrum antimicrobials indirectly suggests a role for intestinal microflora synthesized menaquinone (MK) in the maintenance of normal coagulation. Nonetheless, no direct evidence is available to support this contention. OBJECTIVE: Our objective was therefore to provide evidence that bacterially produced MK may be absorbed by the distal small bowel of humans. METHODS: Using a cell harvester, Staphylococcus aureus (ATCC 29213) was grown in 12-L batches, harvested, and extracted by high performance liquid chromatography (HPLC) to obtain 8 mg of pure MK. Four normal volunteers were placed on a diet severely restricted in vitamin K1 (median 32-40 U/day), and were given warfarin to maintain an International Normalized Ratio of approximately 2.0. On the 10th day of warfarin administration, naso-ileal intubation was performed and 1.5 mg of MK was delivered into the ileum. PT, factor VII, II and serum vitamin K1 levels were monitored throughout the study. RESULTS: Mean serum vitamin K1 levels were reduced to 30% of the pre-diet value at the time of MK administration. Within 24 h of ileal MK administration, there was a significant (p < 0.05) increase in the factor VII level of 0.28 +/- 0.10 U/ml (mean +/- SEM) and a significant decrease of 2.5 (+/- 0.1) s in the PT, whereas in the control phase (during which no MK was administered), there were no significant changes in the PT or factor VII at corresponding time intervals. CONCLUSION: These data provide direct evidence for the absorption of vitamin K2 from the distal small bowel, supporting a definite role for bacterially synthesized vitamin K2 in contributing to the human nutritional requirements of this vitamin. PMID- 8198106 TI - Bacterial endocarditis in patients with chronic liver disease. AB - OBJECTIVE: Although patients with cirrhosis have an increased susceptibility for bacterial infections, endocarditis complicating cirrhosis has been reported only infrequently. In this study, our objective was to determine whether, bacterial endocarditis is, in fact, a complicating factor in cirrhosis. METHODS: We retrospectively studied all cases of bacterial endocarditis that occurred over the last 15 yr in patients with known cirrhosis. RESULTS: Ten patients (three males, seven females) were identified, whose mean age was 55 yr (range 29-65 yr). Bacterial organisms included Staphylococcus aureus, coagulase-positive (eight patients), Peptostreptococcus (one patient), and Enterococcus (one patient). Underlying liver disease consisted of alcoholism (five patients), autoimmune chronic active hepatitis (two), cryptogenic cirrhosis (two), and primary biliary cirrhosis (one). Distribution of heart valves affected were mitral valve (six), aorta (two), and there were two involving both mitral and aortic valves. Echocardiograms revealed vegetation in 50% of the patients. Laboratory studies were markedly abnormal, with mean values of albumin 2.4 mg/dl, creatinine 2.5 mg/dl, BUN 76.5 mg/dl, and total bilirubin 8.2 mg/dl. Potential associated sources of infection were upper gastrointestinal bleeding (four), pneumonia (two), and one each of spontaneous bacterial peritonitis, hip replacement, heart catheterization, and abdominal abscess. The outcome was poor, with death in eight of 10 patients. CONCLUSIONS: Bacterial endocarditis may complicate cirrhosis, may be more frequent in females, typically involves the mitral valve, and probably is due to Staphylococcus aureus. PMID- 8198107 TI - Hereditary pancreatitis. AB - Hereditary pancreatitis is an idiopathic form of chronic pancreatitis which affects multiple members of a family in an autosomal dominant mode of inheritance. Most of the case reports are in caucasians of European descent. In this report, we present our data on four affected members spanning three generations in a family from India. Current data on hereditary pancreatitis are summarized, to revive an interest in this rare form of chronic pancreatitis. PMID- 8198108 TI - Fulminant ulcerative colitis in pregnancy. AB - Most pregnant women with a history of ulcerative colitis will have a normal pregnancy and deliver a healthy child. Medical therapy can usually control the disease in those patients who experience an exacerbation, and only a minority of women progress to severe colitis necessitating surgery in pregnancy. We describe a woman who developed colitis in the first weeks of pregnancy that initially responded to steroid enemas. She then relapsed and progressed to severe colitis requiring a sub-total colectomy in the 26th wk of pregnancy. This was complicated by intra-abdominal sepsis and an abscess that required drainage. She successfully completed pregnancy, to be delivered of a healthy daughter in the 32nd wk of pregnancy. PMID- 8198109 TI - Eosinophilic mucosal infiltrate in infants with congenital gastrointestinal obstruction. AB - Infiltration of the antrum and small bowel with eosinophils has been reported to be the etiologic factor for intestinal obstruction in adults with eosinophilic gastroenteritis. We report a case of a breast-fed 8-month-old infant with eosinophilic gastroenteritis (EGE), who presented with severe hematemesis and congenital obstruction of the duodenum, to emphasize that not all obstructive symptoms associated with EGE are secondary to eosinophilic infiltration. Our patient displayed many of the classic signs and symptoms of EGE, including an elevated absolute eosinophil count and marked eosinophilic infiltration in mucosal biopsies from the duodenum, stomach, and esophagus. At surgery there was marked dilation of the first portion of the duodenum and obstruction of the second portion due to malrotation of the intestine with Ladd's bands, duodenal stenosis, and annular pancreas. The dramatic clinical response to surgical correction of the duodenal obstruction leaves little doubt that this patient's symptoms were related to the anatomical lesion. PMID- 8198110 TI - Extrahepatic Hodgkin's disease and cholestasis. PMID- 8198111 TI - Toothpick in ano: an unusual cause of syncope. PMID- 8198112 TI - Obstructive jaundice: an unusual presentation of afferent loop obstruction. PMID- 8198113 TI - Bezoar in a Zenker's diverticulum. PMID- 8198114 TI - Omeprazole/amoxicillin versus ranitidine/triple therapy for duodenal ulcer: when is the "same" the same? PMID- 8198115 TI - Cholecystectomy: radiologist to the rescue? PMID- 8198116 TI - Nafcillin-associated jaundice. PMID- 8198117 TI - Effect of calcium intake on the incidence of sporadic colorectal polyps. PMID- 8198118 TI - Esophageal perforation as a complication of endoscopic overtube insertion. PMID- 8198119 TI - Heyde's syndrome: the controversy continues. PMID- 8198120 TI - Absence of seasonal fluctuations in peptic ulcer activity. PMID- 8198121 TI - Bradycardia in shigellosis. PMID- 8198122 TI - Combined endoscopic ultrasound and endoscopic Meltzer-Lyon testing in the diagnosis of cholelithiasis. PMID- 8198123 TI - Mutations in the lysosomal beta-galactosidase gene that cause the adult form of GM1 gangliosidosis. AB - Three adult patients with acid beta-galactosidase deficiency/GM1 gangliosidosis who were from two unrelated families of Scandinavian descent were found to share a common point mutation in the coding region of the corresponding gene. The patients share common clinical features, including early dysarthria, mild ataxia, and bone abnormalities. When cDNA from the two patients in family 1 was PCR amplified and sequenced, most (39/41) of the clones showed a C-to-T transition (C ->T) at nucleotide 245 (counting from the initiation codon). This mutation changes the codon for Thr(ACG) to Met(ATG). Mutant and normal sequences were also found in that position in genomic DNA, indicating the presence of another mutant allele. Genomic DNA from the patient in family 2 revealed the same point mutation in one allele. It was determined that in each family only the father carried the C-->T mutation. Expression studies showed that this mutation produced 3%-4% of beta-galactosidase activity, confirming its deleterious effects. The cDNA clones from the patients in family 1 that did not contain the C-->T revealed a 20-bp insertion of intronic sequence between nucleotides 75 and 76, the location of the first intron. Further analysis showed the insertion of a T near the 5' splice donor site which led to the use of a cryptic splice site. It appears that the C- >T mutation results in enough functional enzyme to produce a mild adult form of the disease, even in the presence of a second mutation that likely produces nonfunctional enzyme. PMID- 8198124 TI - Four novel PEPD alleles causing prolidase deficiency. AB - Mutations at the PEPD locus cause prolidase deficiency (McKusick 170100), a rare autosomal recessive disorder characterized by iminodipeptiduria, skin ulcers, mental retardation, and recurrent infections. Four PEPD mutations from five severely affected individuals were characterized by analysis of reverse transcribed, PCR-amplified (RT-PCR) cDNA. We used SSCP analysis on four overlapping cDNA fragments covering the entire coding region of the PEPD gene and detected abnormal SSCP bands for the fragment spanning all or part of exons 13-15 in three of the probands. Direct sequencing of the mutant cDNAs showed a G-->A, 1342 substitution (G448R) in two patients and a 3-bp deletion (delta E452 or delta E453) in another. In the other two probands the amplified products were of reduced size. Direct sequencing of these mutant cDNAs revealed a deletion of exon 5 in one patient and of exon 7 in the other. Intronic sequences flanking exons 5 and 7 were identified using inverse PCR followed by direct sequencing. Conventional PCR and direct sequencing then established the intron-exon borders of the mutant genomic DNA revealing two splice acceptor mutations: a G-->C substitution at position -1 of intron 4 and an A-->G substitution at position -2 of intron 6. Our results indicate that the severe form of prolidase deficiency is caused by multiple PEPD alleles. In this report we attempt to begin the process of describing these alleles and cataloging their phenotypic expression. PMID- 8198125 TI - A common mutation associated with the Duarte galactosemia allele. AB - The human cDNA and gene for galactose-1-phosphate uridyl transferase (GALT) have been cloned and sequenced. A prevalent mutation (Q188R) is known to cause classic galactosemia (G/G). G/G galactosemia has an incidence of 1/38,886 in 1,396,766 Georgia live-born infants, but a more common variant of galactosemia, Duarte, has an unknown incidence. The proposed Duarte biochemical phenotypes of GALT are as follows: D/N, D/D, and D/G, which have approximately 75%, 50%, and 25% of normal GALT activity respectively. In addition, the D allele has isoforms of its enzyme that have more acidic pI than normal. Here we systematically determine (a) the prevalence of an A-to-G transition at base pair 2744 of exon 10 in the GALT gene, transition that produces a codon change converting asparagine to aspartic acid at position 314 (N314D), and (b) the association of this mutation with the Duarte biochemical phenotype. The 2744G nucleotide change adds an AvaII (SinI) cut site, which was identified in PCR-amplified DNA. In 111 biochemically unphenotyped controls with no history of galactosemia, 13 N314D alleles were identified (prevalence 5.9%). In a prospective study, 40 D alleles were biochemically phenotyped, and 40 N314D alleles were found. By contrast, in 36 individuals known not to have the Duarte biochemical phenotype, no N314D alleles were found. We conclude that the N314D mutation is a common allele that probably causes the Duarte GALT biochemical phenotype and occurs in a predominantly Caucasian, nongalactosemic population, with a prevalence of 5.9%. PMID- 8198126 TI - Notes on individual sequence variation in humans: immunoglobulin kappa light chain. AB - Little is known concerning the magnitude of variability in the nucleic acid sequence of DNA at the individual level. We have collected a large set of sequence data from the human immunoglobulin kappa light-chain-locus constant region (10,444 bp) and subgroup IV variable region (18,580 bp). For the constant region, absolute conservation of sequence was observed, even in intron and coding region silent sites, with the exception of one previously defined polymorphic site. For the variable region, 12 heterozygous positions were identified, giving a heterozygosity of 6 x 10(-4) per nucleotide site. The amount of nucleic acid sequence variation differs significantly (chi 2 = 4.88) between these two regions, and the observed variation is two orders of magnitude lower than that reported for two Drosophila melanogaster loci. These data suggest that, for at least some regions of the human genome, nucleic acid sequence may be less variable than previously estimated. PMID- 8198127 TI - The genetic locus for free sialic acid storage disease maps to the long arm of chromosome 6. AB - Salla disease (SD), or adult-type free sialic acid storage disease, is an autosomal recessive lysosomal storage disorder characterized by impaired transport of free sialic acid across the lysosomal membrane and severe psychomotor retardation. Random linkage analysis of a sample of 27 Finnish families allowed us to localize the SD locus to the long arm of chromosome 6. The highest lod score of 8.95 was obtained with a microsatellite marker of locus D6S286 at theta = .00. Evidence for linkage disequilibrium was observed between the SD locus and the alleles of three closely linked markers, suggesting that the length of the critical region for the SD locus is in the order of 190 kb. PMID- 8198128 TI - Recombinations in individuals homozygous by descent localize the Friedreich ataxia locus in a cloned 450-kb interval. AB - The locus for Friedreich ataxia (FRDA), a severe neurodegenerative disease, is tightly linked to markers D9S5 and D9S15, and analysis of rare recombination events has suggested the order cen-FRDA-D9S5-D9S15-qter. We report here the construction of a YAC contig extending 800 kb centromeric to D9S5 and the isolation of five new microsatellite markers from this region. In order to map these markers with respect to the FRDA locus, all within a 1-cM confidence interval, we sought to increase the genetic information of available FRDA families by considering homozygosity by descent and association with founder haplotypes in isolated populations. This approach allowed us to identify one phase-known recombination and one probable historic recombination on haplotypes from Reunion Island patients, both of which place three of the five markers proximal to FRDA. This represents the first identification of close FRDA flanking markers on the centromeric side. The two other markers allowed us to narrow the breakpoint of a previously identified distal recombination that is > 180 kb from D9S5 (26P). Taken together, the results place the FRDA locus in a 450-kb interval, which is small enough for direct search of candidate genes. A detailed rare cutter restriction map and a cosmid contig covering this interval were constructed and should facilitate the search of genes in this region. PMID- 8198129 TI - Hereditary nonpolyposis colon cancer: analysis of linkage to 2p15-16 places the COCA1 locus telomeric to D2S123 and reveals genetic heterogeneity in seven Canadian families. AB - Hereditary nonpolyposis colon cancer (HNPCC) is an autosomal dominant trait responsible for approximately 6% of colorectal cancers. Linkage of the HNPCC trait to the D2S123 locus on 2p15-16 has previously been reported in two families. This HNPCC locus is now designated "COCA1." We have tested seven Canadian HNPCC families, who have a variety of clinical presentations, for linkage to a panel of microsatellite polymorphisms in the vicinity of D2S123. One family was clearly linked to the COCA1 locus (LOD = 4.21), and a second family is likely to be linked (LOD = 0.92). In three families linkage was excluded. In the remaining two families the data were inconclusive. In the linked family, individuals with cancer of the endometrium or ureter share a common haplotype with 12 family members with colorectal cancer. This supports the suspected association between these extracolonic neoplasms and the HNPCC syndrome. In addition, five of the six individuals with adenomatous polyps (but no colorectal cancer) have the same haplotype as the affected individuals, while the sixth carries a recombination. One individual with colorectal cancer carries a recombination that places the COCA1 locus telomeric to D2S123. This study localizes the COCA1 gene to an 8-cM region that is consistent with the location of the hMSH2 gene. We also confirm that families presently classified as HNPCC are genetically heterogeneous. PMID- 8198130 TI - The tyrosinase-positive oculocutaneous albinism gene shows locus homogeneity on chromosome 15q11-q13 and evidence of multiple mutations in southern African negroids. AB - Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal recessive disorder of the melanin pigmentary system. South African ty-pos OCA individuals occur with two distinct phenotypes, with or without darkly pigmented patches (ephelides, or dendritic freckles) on exposed areas of the skin. These phenotypes are concordant within families, suggesting that there may be more than one mutation at the ty-pos OCA locus. Linkage studies carried out in 41 families have shown linkage between markers in the Prader-Willi/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13 and ty-pos OCA. Analysis showed no obligatory crossovers between the alleles at the D15S12 locus and ty-pos OCA, suggesting that the D15S12 locus is very close to or part of the disease locus, which is postulated to be the human homologue, P, of the mouse pink-eyed dilution gene, p. Unlike caucasoid "ty-pos OCA" individuals, negroid ty-pos OCA individuals do not show any evidence of locus heterogeneity. Studies of allelic association between the polymorphic alleles detected at the D15S12 locus and ephelus status suggest that there was a single major mutation giving rise to ty-pos OCA without ephelides. There may, however, be two major mutations causing ty-pos OCA with ephelides, one associated with D15S12 allele 1 and the other associated with D15S12 allele 2. The two loci, GABRA5 and D15S24, flanking D15S12, are both hypervariable, and many different haplotypes were observed with the alleles at the three loci on both ty-pos OCA-associated chromosomes and "normal" chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198132 TI - A sib-pair approach to interval mapping of quantitative trait loci. AB - An interval mapping procedure based on the sib-pair method of Haseman and Elston is developed, and simulation studies are carried out to explore its properties. The procedure is analogous to other interval mapping procedures used with experimental material, such as plants and animals, and yields very similar results in terms of the location and effect size of a quantitative trait locus (QTL). The procedure offers an advantage over the conventional Haseman and Elston approach, in terms of power, and provides useful information concerning the location of a QTL. Because of its simplicity, the method readily lends itself to the analysis of selected samples for increased power and the evaluation of multilocus models of complex phenotypes. PMID- 8198131 TI - Interstitial deletions are not the main mechanism leading to 18q deletions. AB - Most patients who present with the 18q- syndrome have an apparent terminal deletion of the long arm of chromosome 18. For precise phenotypic mapping of this syndrome, it is important to determine whether the deletions are terminal deletions or interstitial deletions. A human telomeric YAC clone has been identified that hybridizes specifically to the telomeric end of 18q. This clone was characterized and used to analyze seven patients with 18q deletions. By FISH and Southern blotting analysis, all patients were found to lack this chromosomal region on their deleted chromosome, demonstrating that the patients do not have cryptic interstitial deletions. PMID- 8198133 TI - Computation of identity-by-descent proportions shared by two siblings. AB - I provide a novel approach to computing the mean and variance of the proportion of genetic material shared identical by descent (IBD) by sibling pairs in a specified chromosomal region, conditional on observed marker data. I first show that each chromosome in an offspring can be represented by a two-state Markov chain, with the time parameter being the map distance along the chromosome. On this basis, I show that IBD proportion can be written as a stochastic integral and that the computation of its mean and variance can be reduced to evaluation of an integral of some elementary functions. In addition, I show how Goldgar's model can be extended to include dominance effects. Several examples are provided to illustrate the calculation. PMID- 8198134 TI - Detection of tandem duplications and implications for linkage analysis. AB - The first demonstration of an autosomal dominant human disease caused by segmental trisomy came in 1991 for Charcot-Marie-Tooth disease type 1A (CMT1A). For this disorder, the segmental trisomy is due to a large tandem duplication of 1.5 Mb of DNA located on chromosome 17p11.2-p12. The search for the CMT1A disease gene was misdirected and impeded because some chromosome 17 genetic markers that are linked to CMT1A lie within this duplication. To better understand how such a duplication might affect genetic analyses in the context of disease gene mapping, we studied the effects of marker duplication on transmission probabilities of marker alleles, on linkage analysis of an autosomal dominant disease, and on tests of linkage homogeneity. We demonstrate that the undetected presence of a duplication distorts transmission ratios, hampers fine localization of the disease gene, and increases false evidence of linkage heterogeneity. In addition, we devised a likelihood-based method for detecting the presence of a tandemly duplicated marker when one is suspected. We tested our methods through computer simulations and on CMT1A pedigrees genotyped at several chromosome 17 markers. On the simulated data, our method detected 96% of duplicated markers (with a false positive rate of 5%). On the CMT1A data our method successfully identified two of three loci that are duplicated (with no false positives). This method could be used to identify duplicated markers in other regions of the genome and could be used to delineate the extent of duplications similar to that involved in CMT1A. PMID- 8198135 TI - Additive influence of maternal and offspring DM-kinase gene CTG repeat lengths in the genesis of congenital myotonic dystrophy. PMID- 8198136 TI - Molecular characterization of both alleles in an unusual Tay-Sachs disease B1 variant. PMID- 8198137 TI - DNA data banking: a cautionary tale. PMID- 8198138 TI - A review of state legislation on DNA forensic data banking. AB - Recent advances in DNA identification technology are making their way into the criminal law. States across the country are enacting legislation to create repositories for the storage both of DNA samples collected from convicted offenders and of the DNA profiles derived from them. These data banks will be used to assist in the resolution of future crimes. This study surveys existing state statues, pending legislation, and administrative regulations that govern these DNA forensic data banks. We critically analyzed these laws with respect to their treatment of the collection, storage, analysis, retrieval, and use of DNA and DNA data. We found much variation among data-banking laws and conclude that, while DNA forensic data banking carries tremendous potential for law enforcement, many states, in their rush to create data banks, have paid little attention to issues of quality control, quality assurance, and privacy. In addition, the sweep of some laws is unnecessarily broad. Legislative modifications are needed in many states to better safeguard civil liberties and individual privacy. PMID- 8198139 TI - Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia I. AB - Trinucleotide repeat expansion has been found in 64 subjects from 19 families: 57 patients with SCA1 and 7 subjects predicted, by haplotype analysis, to carry the mutation. Comparison with a large set of normal chromosomes shows two distinct distributions, with a much wider variation among expanded chromosomes. The sex of transmitting parent plays a major role in the size distribution of expanded alleles, those with > 54 repeats being transmitted by affected fathers exclusively. Our data suggest that alleles with > 54 repeats have a reduced chance of survival; these appear to be replaced in each generation by further expansion of alleles in the low- to medium-expanded repeat range, preferentially in male transmissions. Detailed clinical follow-up of a subset of our patients demonstrates significant relationships between increasing repeat number on expanded chromosomes and earlier age at onset, faster progression of the disease, and earlier age at death. PMID- 8198140 TI - Platelet-mediated transformation of mtDNA-less human cells: analysis of phenotypic variability among clones from normal individuals--and complementation behavior of the tRNALys mutation causing myoclonic epilepsy and ragged red fibers. AB - In the present work, we demonstrate the possibility of using human blood platelets as mitochondrial donors for the repopulation of mtDNA-less (rho 0) cells. The noninvasive nature of platelet isolation, combined with the prolonged viability of platelet mitochondria and the simplicity and efficiency of the mitochondria-transfer procedure, has substantially increased the applicability of the rho 0 cell transformation approach for mitochondrial genetic analysis and for the study of mtDNA-linked diseases. This approach has been applied to platelets from several normal human individuals and one individual affected by the myoclonic-epilepsy-and-ragged-red-fibers (MERRF) encephalomyopathy. A certain variability in respiratory capacity was observed among the platelet-derived rho 0 cell transformants from a given normal subject, and it was shown to be unrelated to their mtDNA content. The results of sequential transfer of mitochondria from selected transformants into a rho 0 cell line different from the first rho 0 acceptor strongly suggest that this variability reflected, at least in part, differences in nuclear gene content and/or activity among the original recipient cells. A much greater variability in respiratory capacity was observed among the transformants derived from the MERRF patient and was found to be related to the presence and amount of the mitochondrial tRNALys mutation associated with the MERRF syndrome. An analysis of the relationship between proportion of mtDNA carrying the MERRF mutation and degree of respiratory activity in various transformants derived from the MERRF patient revealed an unusual complementation behavior of the tRNALys mutation, possibly reflecting the distribution of mutant mtDNA among the platelet mitochondria. PMID- 8198141 TI - Disease-causing mutations in exon 11 of the medium-chain acyl-CoA dehydrogenase gene. AB - Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most commonly recognized defect of the mitochondrial beta-oxidation in humans. It is a potentially fatal, autosomal recessive inherited defect. Most patients with MCAD deficiency are homozygous for a single disease-causing mutation (G985), causing a change from lysine to glutamate at position 304 (K304E) in the mature MCAD. Only seven non-G985 mutations, all of which are rare, have been reported. Because the G985 mutation and three of the non-G985 mutations are located in exon 11, it has been suggested that this exon may be a mutational hot spot. Here we describe the results from sequence analysis of exon 11 and part of the flanking introns from 36 compound heterozygous patients with MCAD deficiency. We have identified four previously unknown disease-causing mutations (M301T, S311R, R324X, and E359X) and two silent mutations in exon 11. Our results show that exon 11 is not especially mutation prone. We demonstrate that two of the identified disease-causing mutations can be detected by restriction enzyme digestion of the PCR product from the assay for the G985 mutation, a discovery that makes this assay even more useful than before. On the basis of expression of wild-type and mutant MCAD protein in COS-7 cells, we show that the identified mutations abolish MCAD enzyme activity and that they therefore must be disease causing. The M301T, S311R, and K304E mutations are located in helix H, which makes up part of the dimer-dimer interface of the MCAD tetramer. On the basis of the three-dimensional structure of MCAD and the results from the COS-7 expression experiments, we speculate that the primary effect of the M301T and S311R mutations is on correct folding/tetramer assembly, as it has previously been observed for the K304E mutation. PMID- 8198143 TI - Social drinking and the immune response: impairment of lymphokine-activated killer activity. AB - The effect of limited and intermittent alcohol ingestion on the immune response in humans has not been extensively studied. The authors, in this study, evaluate peripheral blood mononuclear cell cytotoxicity before and after alcohol ingestion in a setting designed to mimic social drinking. Eleven healthy volunteers consumed two 12 oz (355 mL) cans of beer in 30 minutes while eating pizza. Five control individuals ingested non-alcoholic beverages. Natural killer and lymphokine-activated killer activity were determined for peripheral blood mononuclear cells obtained before and 30 minutes after alcohol ingestion. Interleukin 2-induced lymphokine-activated killer activity was significantly reduced in blood samples obtained after alcohol ingestion when compared with pre alcohol samples (p < 0.01). Natural killer activity (unstimulated) was not affected by alcohol ingestion. The authors demonstrate that ingestion of a small amount of alcohol impairs the cytotoxic capacity of peripheral blood mononuclear cells. Alcohol in the context of social drinking may have deleterious effects on the immune system's ability to clear virus-infected cells or cells that have undergone neoplastic transformation, especially for individuals with pre-existing immunosuppression. PMID- 8198142 TI - Detection of new paternal dystrophin gene mutations in isolated cases of dystrophinopathy in females. AB - Duchenne muscular dystrophy is one of the most common lethal monogenic disorders and is caused by dystrophin deficiency. The disease is transmitted as an X-linked recessive trait; however, recent biochemical and clinical studies have shown that many girls and women with a primary myopathy have an underlying dystrophinopathy, despite a negative family history for Duchenne dystrophy. These isolated female dystrophinopathy patients carried ambiguous diagnoses with presumed autosomal recessive inheritance (limb-girdle muscular dystrophy) prior to biochemical detection of dystrophin abnormalities in their muscle biopsy. It has been assumed that these female dystrophinopathy patients are heterozygous carriers who show preferential inactivation of the X chromosome harboring the normal dystrophin gene, although this has been shown for only a few X:autosome translocations and for two cases of discordant monozygotic twin female carriers. Here we study X inactivation patterns of 13 female dystrophinopathy patients--10 isolated cases and 3 cases with a positive family history for Duchenne dystrophy in males. We show that all cases have skewed X-inactivation patterns in peripheral blood DNA. Of the nine isolated cases informative in our assay, eight showed inheritance of the dystrophin gene mutation from the paternal germ line. Only a single case showed maternal inheritance. The 10-fold higher incidence of paternal transmission of dystrophin gene mutations in these cases is at 30-fold variance with Bayesian predictions and gene mutation rates. Thus, our results suggest some mechanistic interaction between new dystrophin gene mutations, paternal inheritance, and skewed X inactivation. Our results provide both empirical risk data and a molecular diagnostic test method, which permit genetic counseling and prenatal diagnosis of this new category of patients. PMID- 8198144 TI - In vitro inactivation of pulmonary surfactant replacement preparations by serum albumin. AB - Inactivation of the surface activity of pulmonary surfactant by serum proteins is an important part of neonatal respiratory distress syndrome. The ability of serum proteins to diminish the surface activity of surfactant preparations used to treat respiratory distress syndrome has not been fully described. The sensitivity of clinically useful pulmonary replacement preparations beractant (Survanta) and colfosceril palmitate, cetyl alcohol, and tyloxapol (Exosurf) to albumin inactivation was examined in vitro by the Wilhelmy plate technique. At a final lipid concentration of 0.1 mg/mL and in the absence of albumin, both Survanta and Exosurf exhibited equilibrium surface tensions in the range of 35 dynes/cm. In the presence of albumin, range of 35 dynes/cm. In the presence of albumin, the surface tension of Survanta was markedly higher. Maximal response of Survanta to albumin was observed at about 1 mg/mL protein concentration. When the lipid concentration was raised to 0.3 mg/mL, the presence of albumin had little effect. With Exosurf, the presence of albumin resulted in only minor elevations of surface tension, even at an albumin concentration 10-fold greater than that used in the experiments with Survanta. These results indicate that at lipid concentrations of 0.1 mg/mL and less, the surface activity of the bovine purified lung surfactant Survanta is more sensitive to the presence of albumin than is the synthetic preparation Exosurf. PMID- 8198145 TI - Prevalence of impaired growth in children with homozygous sickle cell anemia. AB - The prevalence of impaired growth was evaluated in 63 patients with homozygous sickle cell anemia. Twenty-five percent of the children studied were less than the fifth percentile of National Center for Health Statistics growth standards for either height/age, weight/age, or weight/height. Significantly more 11- to 18 year-old children were less than the fifth percentile for weight/height compared with earlier age ranges. No differences due to gender were found. Nutritional intervention may improve growth in selected children. PMID- 8198146 TI - Human alveolar macrophage mediated vasodilation and the role of arginine compounds. AB - To determine whether human alveolar macrophages (AM) generate a compound similar to the endothelium-derived relaxing factor, we studied the effect of AM on the isometric response of the pre-contracted rat aorta preparation in the presence and absence of L-arginine or N-substituted L-arginine compounds. Addition of AM to the pre-contracted aorta preparation was ineffective even in the presence of millimolar concentrations of L-arginine. But, AM in the presence of the substituted L-arginine, N alpha-benzoyl L-arginine ethyl ester, significantly increased vasodilation. The enhanced relaxation was associated with an increase in vascular cyclic guanosine 3,5'-monophosphate formation. Hemoglobin and N omega nitro L-arginine methyl ester are inhibitors of the endothelium-dependent relaxation, and both attenuated the vasodilation elicited by AM. Human AM were found to metabolize N alpha-benzoyl L-arginine ethyl ester to a citrulline derivative. No such metabolism was observed with L-arginine. A specific, high pressure liquid chromatographic assay for guanidines revealed that the lack of effect of external L-arginine is not due to the presence of an excess amount of endogenous L-arginine in AM. These results demonstrate that nonactivated human AM, unlike rodent macrophages, possess an enzyme system(s) that metabolize(s) arginine derivatives but not L-arginine to a vasodilator, and this vasodilator has properties similar to that of endothelium-derived relaxing factor. This human AM-derived vasodilator may have an important role in regulating airway smooth muscle function. PMID- 8198147 TI - Case report: the anticardiolipin (antibody) syndrome. AB - The anticardiolipin antibody syndrome is relatively uncommon. It should be suspected mostly in young people with unexplained embolic or thrombotic events. A young patient with an abnormal prothrombin time, partial thromboplastin time, or venereal disease research lab test with one of the above noted vascular events would be a suspect for this disorder. Though an antibody test that will qualitatively and quantitatively measure antiphospholipid antibodies is available, its clinical application is not entirely clear. The presence of the antibody will support a diagnosis but cannot be used alone for diagnosis or treatment. PMID- 8198148 TI - Case report: actinomycosis: multinodular pulmonary involvement. AB - Previous computed tomography reports of pulmonary actinomycosis most commonly describe single, unilateral parenchymal or pleural masses with or without cavitation. The authors describe a thoracic computed tomograph of histologically proven actinomycosis that revealed multiple, bilateral, small pulmonary parenchymal nodules with an associated liver mass, suggesting hematogenous dissemination to the lungs from the liver via the hepatic veins. PMID- 8198149 TI - Case report: idiopathic hypoparathyroidism co-existing with celiac disease: immunologic studies. AB - Idiopathic hypoparathyroidism (IH) is often an isolated disorder in adults, but in children it is usually a component of the autoimmune polyendocrinopathy syndrome. The authors describe a patient diagnosed with isolated IH at age 57 and celiac disease at age 64. Testing of patients' serum show antibodies of the immunoglobulin A isotype against endomysium, reticulin, and gliadin antigens, as well as immunoglobulin G against gliadin. The circulating immunoglobulins reacted with bovine parathyroid tissue, specifically smooth muscle of the blood vessels and glandular cells, as detected by indirect immunofluorescence. Testing of celiac disease positive sera showed similar parathyroid reactivity. When the patient was placed on a gluten-free diet, endomysial, reticulin, and gliadin antibodies decreased to undetectable levels, which was parallel with disappearance of the parathyroid immunoreactivity. The gluten-free diet also produced severe hypercalcemia that responded to calcitriol withdrawal, and ultimately required a reduction by half of the original calcitriol dose. It is possible that in this case the same antibody or antibodies may have caused both hypoparathyroidism and celiac disease. We conclude that, as in the case of childhood-onset IH variants, patients with late-onset isolated IH should be monitored for additional endocrine and extra-endocrine autoimmune disorders. PMID- 8198150 TI - Case report: Nocardia osteomyelitis. AB - Osteomyelitis is an unusual manifestation of infection with Nocardia spp, and most cases result from direct extension from a primary lung or cutaneous lesion. The authors report what they believe to be the first case of Nocardia vertebral osteomyelitis occurring postoperatively, and review the literature on the 19 previously reported cases of Nocardia osteomyelitis due to hematogenous dissemination or direct inoculation, excluding those occurring from direct extension of a mycetoma or primary lung infection. PMID- 8198151 TI - Ironic catastrophes: one's food--another's poison. AB - Iron deficiency is an important nutritional problem in third world countries because it diminishes work performance. In meat-eating countries, iron excess may be more important than iron deficiency. Heme iron is more efficiently absorbed from the diet than inorganic iron, and iron excess can produce cellular oxidation in association with superoxide dismutase. Metal ion catalysis is linked to aging, coronary artery disease, stroke, carcinogenesis, neurodegenerative disorders, and inflammatory disorders. Prudence is advised in the excessive consumption of meat and iron supplementation of the diet until this process is more thoroughly investigated. PMID- 8198152 TI - Sumatriptan for migraine. PMID- 8198153 TI - Southwestern Internal Medicine Conference: pulmonary complications of high altitude exposure. AB - The primary physiologic disturbance at high altitude is hypoxemia, which leads to a cascade of secondary changes in each step of the oxygen-transport chain. The author, in this review, focuses on the alterations in ventilatory control and alveolar-capillary gas exchange at high altitude and discusses the clinical pulmonary complications associated with these alterations, as well as their prevention and management. PMID- 8198154 TI - Honoring the history of the Edward Jackson Memorial Lecture. The L Edward Jackson Memorial Lecture. Part 1. AB - The occasion of the 50th Edward Jackson Memorial Lecture provides an opportunity to look back on the history of the lecture that honors the memory of one of the most outstanding ophthalmologists of modern times. A review is provided as to how the lecture was established after Dr. Jackson's death in 1942 and how the memorial lecturers are chosen. There is a brief glimpse into the life, accomplishments, and personality of Dr. Jackson, and past Jackson lectures are highlighted to demonstrate the breadth of topics and their significance to the advancement of medicine and ophthalmology. In particular, two Jackson Memorial Lectures on the subjects of genetics and glaucoma are discussed since they fit well into the 40-year anniversary of the discovery, in 1953, of the DNA double helix. PMID- 8198155 TI - Genetic clues to glaucoma's secrets. The L Edward Jackson Memorial Lecture. Part 2. AB - Major advances in the medical and surgical treatment of glaucoma have occurred since the first Edward Jackson Memorial lecture was delivered 50 years ago. Collaborative clinical trials under the sponsorship of the National Eye Institute are adding to our knowledge about which patients to treat and how to treat them. Despite these clinical advances, an understanding of the pathophysiologic and biochemical mechanisms that cause the disease remain unknown. The 40th anniversary of the discovery of the DNA double helix provides a springboard for a historical perspective on the heritability of glaucoma. A large pedigree is presented of a family with autosomal dominantly inherited primary open-angle glaucoma of juvenile onset. This is the second family with this clinical entity to show genetic linkage to the long arm of chromosome 1. Other forms of primary open-angle glaucoma with adult onset are presented wherein the inheritance pattern suggests autosomal recessive transmission. Thus far, linkage analysis does not suggest a genetic relationship to the autosomal dominant juvenile-onset pedigree that links to the long arm of chromosome 1. It is hoped that an emphasis on clinical and molecular genetic studies of glaucoma will yield protein defects that can be targeted for treatment. It is emphasized that the clinical ophthalmologist can participate in this important work by finding families with glaucoma and collaborating with individuals capable of extracting DNA, manipulating it, and performing genetic linkage and positional cloning studies. PMID- 8198156 TI - Combined timolol and pilocarpine vs pilocarpine alone and timolol alone in the treatment of glaucoma. AB - We compared the effects of pilocarpine 4% alone, timolol 0.5% alone, and a combination of timolol 0.5% and pilocarpine 4% in the treatment of glaucoma. We treated 43 patients with glaucoma using each drug and then with the combination of drugs for four weeks each. Only patients with a morning intraocular pressure of at least 24 mm Hg without treatment were included. The patients were examined, after one and four weeks of treatment with pilocarpine, timolol, or combined timolol 0.5% and pilocarpine 4%, before the morning dose and at two and five hours after it. At the end of the study, the mean reduction in intraocular pressure from baseline was 9.2 +/- 5.1 mm Hg (28.5% +/- 12.7%) with combined timolol 0.5% and pilocarpine 4%, 5.6 +/- 3.6 mm Hg (17.6% +/- 9.7%) with pilocarpine, and 7.5 +/- 5.0 mm Hg (21.2% +/- 12.6%) with timolol. Intraocular pressure was consistently lower with the combination treatment than with timolol or pilocarpine alone. We believe that this combined solution of timolol pilocarpine is a valuable contribution to the treatment of open-angle glaucoma. PMID- 8198157 TI - Optic disk appearance in ocular hypertensive eyes. AB - We examined the optic disk appearance in ocular hypertensive eyes that had a normal result of conventional computed perimetry. Color stereo-optic disk photographs of 104 ocular hypertensive subjects and of 216 normal individuals were morphometrically evaluated. In the ocular hypertensive eyes as compared to the normal eyes, significant differences (P < .0001) were detected for a smaller area and an abnormal shape of the neuroretinal rim, larger zones alpha and beta of the parapapillary chorioretinal atrophy, a decreased visibility of the retinal nerve fiber layer, and a higher frequency of localized nerve fiber layer defects. The variables most useful to indicate optic nerve damage were an abnormal shape of the neuroretinal rim and a decreased visibility of the nerve fiber layer. The most specific variable was the presence of localized retinal nerve fiber layer defects. Evaluation of these variables may be helpful for the early diagnosis of glaucoma. PMID- 8198158 TI - Distribution and characterization of sulfated proteoglycans in the trabecular tissue of goniodysgenetic glaucoma. AB - We evaluated histochemically the distribution of proteoglycans in the trabecular tissue of goniodysgenetic (developmental) glaucoma. Nine trabecular tissue specimens obtained at trabeculectomy from seven patients with goniodysgenetic glaucoma were stained with either cuprolinic blue or cupromeronic blue in combination with a series of enzyme and nitrous acid treatments. Within the extracellular matrix of the trabecular meshwork, many cupromeronic blue- or cuprolinic blue-positive filaments were observed in association with collagen fibrils, basal lamina, and basal lamina-like material. The extracellular matrices of elastin-like fibers, fine fibrillar materials, and fine granular materials were free from any reaction products. The enzyme and nitrous acid treatments disclosed that the reaction products associated with collagen fibrils represented both chondroitin sulfate and dermatan sulfate types, while those with basal lamina and basal lamina-like material represented heparan sulfate-type proteoglycans. Extensive accumulations of basal lamina-like material contained a great deal of heparan sulfate-type proteoglycans in the thick subcanalicular tissue of goniodysgenetic glaucoma. These results indicate that the class and distribution of proteoglycans in the goniodsygenetic trabecular tissues are virtually the same as that in the normal tissues. However, the large accumulation of basal lamina-like material with heparan sulfate-type proteoglycans can be one of the causes of the intraocular pressure increase in goniodysgenetic glaucoma. PMID- 8198159 TI - The influence of patient reliability on visual field outcome. AB - The reliability of subjects to perform to perimetry correctly should be carefully evaluated to interpret visual field examinations adequately. Clinicians generally agree that numerous false-positive responses to catch trials cause measured thresholds to be falsely high and numerous false-negative responses cause measured thresholds to be falsely low. We studied the effect of false-positive and false-negative responses on the outcome of visual field measurements. Of 47 eyes, the results of 106 stable glaucomatous visual field tests (Program G1, Octopus 201, Interzeag, Schlieren, Switzerland) with false-positive responses and no more than one false-negative response to catch trials were compared to the results of reliable visual field tests (no false-positive and no more than one false-negative response) performed on the same eye. Similarly, 60 stable visual fields with false-negative responses and no more than one false-positive response were used to study the effect of false-negative responses on visual field sensitivities. Linear regression analysis disclosed a mean sensitivity increase of 1.5 dB for every 10% of false-positive responses (r = .34, P = .000) and a mean sensitivity decrease of 1.2 dB for every 10% of false-negative responses (r = .26, P = .04). These results may be used to help reduce the magnitude of unexplained long-term fluctuation in visual field interpretation. PMID- 8198160 TI - Differentiating macular holes from macular pseudoholes. AB - Surgical treatments of macular holes have become increasingly effective in inducing resolution of the cuff of surrounding subretinal fluid, resulting in increased vision in many patients. However, for many conditions that mimic a macular hole, either surgery is not indicated or different surgical manipulations are necessary. Differentiating macular holes from some forms of macular pseudoholes can be difficult or impossible based solely on clinical examination. Adjunctive tests that may enhance the accuracy of diagnosis are either not feasible or not available to most clinical practices. We evaluated three clinic based tests for their value in allowing the differentiation between macular holes and macular pseudoholes: Amsler grid testing, Watzke-Allen sign, and laser aiming beam test. These tests were evaluated in three groups of clinically defined patients: those with full-thickness macular holes, those with macular pseudoholes, and those who had previously undergone successful macular hole treatment. Although the Amsler grid testing was sensitive in correlating with clinically defined macular holes, it was not specific. The Watzke-Allen sign and, to a greater extent, the laser aiming beam test were extremely sensitive and specific in correlating clinically defined full-thickness macular holes and pseudoholes. These tests improve the accuracy of diagnosis of full-thickness macular holes. PMID- 8198161 TI - Studies of the blood-aqueous barrier in diabetes mellitus. AB - We measured the breakdown of the blood-aqueous barrier in 63 patients with diabetes (126 eyes) by using a laser flare meter. Of 126 eyes, 40 had no retinopathy, 34 had proliferative retinopathy, 24 had regressed proliferative retinopathy, 14 had background retinopathy, and 14 had maculopathy. Eyes were classified into one category only. Mean flare was greater for proliferative retinopathy compared to background retinopathy (P = .0065), no retinopathy (P = .0001), and maculopathy (P = .0189). Flare values were greater for regressed proliferative retinopathy compared to no retinopathy (P = .0118) (paired Student's t-test). Diabetic eyes without demonstrable retinopathy still had higher flare values than control eyes without diabetes. The length of diabetes was greater for those eyes with proliferative diabetic retinopathy (P = .0195), regressed proliferative diabetic retinopathy (P = .0625), and background diabetic retinopathy (P = .006) compared to those with no retinopathy. No significant difference was noted in duration of diabetes for eyes with diabetic maculopathy when compared to those with no retinopathy (P = .5788). Breakdown of the blood aqueous barrier precedes the development of retinopathy, and the more severe proliferative forms have greater blood-aqueous barrier dysfunction. PMID- 8198162 TI - Combined daily therapy with intravenous ganciclovir and foscarnet for patients with recurrent cytomegalovirus retinitis. AB - We treated seven patients (nine eyes) who had cytomegalovirus retinitis with daily intravenous ganciclovir plus foscarnet. All patients had demonstrated multiple progressions of retinitis on single-drug therapy, and some were intolerant to induction doses of one or both medications. Before combination therapy, the median number of progressions was five per patient. The mean interval between progressions was 11 weeks, and the mean interval before the final progression was four weeks. While taking combination therapy, two patients showed progression after 14 and 34 weeks. Two patients showed no progression after 17 and 36 weeks of follow-up. Three patients died after five, 14, and 23 weeks, respectively, without progression of retinitis. In every patient, the progression-free interval was longer during combination therapy than the previous progression-free interval during single-drug therapy. In no case was combination therapy stopped because of toxicity. Combination therapy was fairly well tolerated and appeared to prolong the interval to progression and to preserve vision in our patients. PMID- 8198163 TI - Erbium:YAG laser photothermal retinal ablation in enucleated rabbit eyes. AB - The erbium:YAG laser has been shown to produce precise tissue ablation because of the high water absorption of the 2.94-microns wave-length emitted by this laser. We used an experimental system to create lesions of various depths in the surface of the rabbit retina in enucleated eyes in vitro to examine the potential application to maneuvers such as retinotomy and the removal of epiretinal membranes in vitrectomy. With an air/retinal interface, single pulses produced discrete craters in the retinal surface with a depth proportional to fluence, ranging from 30 microns for a pulse of 1.3 J/cm2 to a full-thickness retinotomy at 3.9 J/cm2. An adjacent zone of coagulated tissue ranging in size from 15 to 40 microns was noted. Multiple pulses had an additive effect. With a fluid/retinal interface, 20 pulses of 3.6 J/cm2 produced a full-thickness retinotomy, with an adjacent zone of damaged tissue up to 1 mm, caused by effects of volatilization of intervening fluid. The erbium:YAG laser may have a role in vitreoretinal surgery. PMID- 8198164 TI - Length-tension properties of extraocular muscles in patients with esotropia and intermittent exotropia. AB - The purpose of this study was to determine the passive length-tension characteristics of horizontal recti muscles in patients with non-restrictive horizontal strabismus. A system to measure intraoperative continuous-registration passive length-tension curves of detached extraocular muscles was designed. The size of the preoperative deviation and the change in the deviation as a result of surgery was correlated with the passive tension of the medial rectus muscle in patients with acquired esotropia. Patients with infantile esotropia or intermittent exotropia showed no relationship between passive tension and either preoperative deviation or response to surgery. Surgical recession of both the medial and lateral recti muscles produced large changes in the passive tension characteristics of both of these muscles. Medial rectus muscle recession produced larger changes in the passive tension than equal amounts of recession of lateral recti muscles. PMID- 8198165 TI - Low-energy argon laser suture lysis after trabeculectomy. PMID- 8198166 TI - Normal intraocular pressure in premature infants. PMID- 8198167 TI - Polymerase chain reaction for the detection of Mycobacterium tuberculosis in ocular tuberculosis. PMID- 8198168 TI - Retinal angiopathy resembling unilateral frosted branch angiitis in a patient with relapsing acute lymphoblastic leukemia. PMID- 8198169 TI - Transplantation of corneal tissue from a blind eye to a high-risk fellow eye by bilateral penetrating keratoplasty. PMID- 8198170 TI - Epithelial distortions at the ablation zone margin after excimer laser photorefractive keratectomy for myopia. PMID- 8198171 TI - Magnetic resonance imaging findings in oculopalatal myoclonus. PMID- 8198172 TI - Horner's syndrome after tonsillectomy. PMID- 8198173 TI - Surgical management of acquired lacrimal sac diverticula. PMID- 8198174 TI - The clinonasal line as a reproducible reference guide for optic canal imaging. PMID- 8198175 TI - Loss of accommodation as the first symptom of cataract. PMID- 8198176 TI - Tobacco amblyopia. PMID- 8198177 TI - Capillary blood flow velocity measurements in cystoid macular edema with the scanning laser ophthalmoscope. PMID- 8198178 TI - Risk factors for development of rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis. PMID- 8198179 TI - Optic disk risk factors for nonarteritic anterior ischemic optic neuropathy. PMID- 8198180 TI - The pros and cons of laser dacryocystorhinostomy. PMID- 8198181 TI - Cervical spinal stenosis and stingers in collegiate football players. AB - We evaluated the relationship of cervical spinal stenosis with the occurrence of "stingers" in collegiate football players who participated at our institution from 1987 through 1991. Preparticipation cervical spine radiographs of 266 players were used to measure Torg ratio. Forty players with stingers were identified: 34 had an extension-compression mechanism; 6 had a brachial plexus stretch mechanism. Time-loss neck injuries occurred in 31 players; the remaining 195 players were asymptomatic. The mean Torg ratio was significantly smaller for the stinger group (P = 0.02). The Torg ratio was less than 0.8 at 1 or more levels in 47.5% of the stinger group, 32.3% of the time-loss neck pain group, and 25.1% of the asymptomatic group. No player with a brachial plexus stretch mechanism had a mean Torg ratio less than 0.8, but 20.6% of the players with an extension-compression mechanism had a mean Torg ratio less than 0.8. Players with a Torg ratio less than 0.8 had 3 times the risk of incurring stingers. We conclude that cervical spinal stenosis increases the risk for having stingers with complicated clinical courses. PMID- 8198182 TI - Cervical spine injury, hockey helmets, and face masks. AB - Over the past 30 years hockey players began wearing helmets and face masks. Cervical spine injury, with an incidence of 15 cases per year, began to be reported in the 1980s. Cervical spine trauma had not been reported before then. After review of the literature, there seems to be a consensus of opinion that the style of play that is allowed a player with head protection may actually increase the chances of cervical spinal trauma. PMID- 8198183 TI - Posterior ossification of the shoulder: the Bennett lesion. Etiology, diagnosis, and treatment. AB - We report a series of ossific lesions of the posterior inferior glenoid in a group of elite baseball players. We hope to clarify the etiology, diagnosis, and treatment of the Bennett lesion. From August 1985 to August 1991, we identified six professional baseball pitchers and one college pitcher with evidence of ossification of the shoulder on plain radiographs, computed tomography, or magnetic resonance imaging. Arthroscopic examination was performed in all cases. All seven players had identifiable posterior labral injury on arthroscopic examination; six of these seven also had varying degrees of undersurface posterior rotator cuff damage. No anterior tissue damage, anterior instability, or subacromial impingement was noted. No ossification was identified arthroscopically. Intraarticular labral and rotator cuff tears were debrided arthroscopically and patients underwent rehabilitation for 4 to 6 months after surgery. Six of the seven athletes returned to preinjury performance levels; however, one pitcher is no longer playing competitive baseball. The Bennett lesion is an extraarticular posterior ossification associated with posterior labral injury and posterior undersurface rotator cuff damage. It is not, however, a result of traction stresses in the region of the triceps insertion. Recognition is important for identification and treatment of the lesion and associated pathologic damage. PMID- 8198184 TI - An evaluation of the shoulder relocation test. AB - The purpose of this study was to evaluate the sensitivity, specificity, negative and positive predictive values, and accuracy of the shoulder relocation test in 100 patients who underwent shoulder surgery. Based on operative data and examination under anesthesia, the diagnoses were grouped into six categories: anterior instability (without cuff disease), posterior instability, rotator cuff disease (without associated anterior instability), acromioclavicular disorder, osteoarthrosis, and instability of the biceps tendon. The test was performed on the day of surgery by placing the arm in a position of 90 degrees of humerothoracic abduction and 90 degrees of external rotation (90 degrees/90 degrees). Patient responses of pain and apprehension (considered separately) were assessed in this position both with and without application of an anterior force to the proximal humerus. The relocation test assessed diminution of pain and apprehension after application of a posteriorly directed force to the proximal humerus relative to the position of 90 degrees/90 degrees alone and to the position of an anterior force being applied to the proximal humerus. Overall, 63 patients reported pain with 90 degrees/90 degrees; 74 reported pain when an anterior force to the proximal humerus was applied: the anterior instability group alone had 46 and 63 reports of pain, respectively; the rotator cuff group alone had 82 and 88 reports of pain, respectively. The only positive responses for apprehension were in the anterior instability group, of which 63% had apprehension with 90 degrees/90 degrees alone and 74 had apprehension when an anterior humeral force was applied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198185 TI - The surgical treatment of arthrofibrosis of the knee. AB - Sixty-one lysis of adhesion procedures were performed for arthrofibrosis of the knee between 1981 and 1990. In 43 cases (37 patients) the etiology was prior knee ligament surgery. Ten cases had sustained fractures about the knee and eight had miscellaneous etiologies. Six patients required a second lysis of adhesion procedure. A retrospective analysis of the 43 ligament patients was undertaken to evaluate the results of surgical treatment. All 43 cases were available for followup at an average of 3.6 years. Surgical indications included flexion or extension deficits of > or = 10 degrees or when motion failed to improve despite 2 months of intense therapy. Follow-up assessment included clinical and radiographic evaluation. Flexion improved from 83% to 97% of the contralateral side. Extension deficits improved from 14 degrees to 3 degrees. Only 23 of 37 patients (62%) achieved satisfactory functional results. Radiographic evidence of degenerative changes, soft tissue calcification, and patella infera was found in 89%, 51%, and 9% of the patients, respectively. Patients requiring surgical treatment for arthrofibrosis after knee ligament surgery achieved excellent motion gains, but functional outcome scores were compromised and radiographic findings were concerning. Patients with the localized anterior intraarticular variant or those undergoing lysis of adhesion surgery sooner than 6 months had outcomes comparable with controls. PMID- 8198186 TI - Outpatient surgical management of arthrofibrosis after anterior cruciate ligament surgery. AB - We present a consecutive series of nine patients who were referred to us because of arthrofibrosis (loss of > 15 degrees of extension) after intraarticular anterior cruciate ligament reconstruction using autogenous patellar tendon (eight patients) or semitendinosus (one patient) graft. Eight patients had surgery within 2 weeks of injury. All patients had been immobilized in flexion after the anterior cruciate ligament reconstruction and they had failed to improve despite vigorous physical therapy and other closed methods of treatment. The mean time from anterior cruciate ligament reconstruction to the subsequent surgery was 10.2 months (range, 3 to 14). The patients underwent an outpatient arthroscopic anterior scar resection, notchplasty, a closed knee manipulation for flexion, and extension casting. Serial daily extension cast changes allowed the patients to obtain full extension, which was maintained by a bivalved extension splint for bedtime use. Flexion was actively sought by aggressive outpatient physical therapy. All patients except one noted near-normal ultimate range of motion. One patient could only attain 10 degrees short of flat extension at the end of his rehabilitation and was considered a failed result. At final followup (mean, 31 months), no patient complained of symptoms of instability, all had a normal gait, and all but one were able to return to athletic activities. PMID- 8198187 TI - Femoral intercondylar notch stenosis and correlation to anterior cruciate ligament injuries. A prospective study. AB - To evaluate the possible relationship between femoral intercondylar notch stenosis and anterior cruciate ligament injuries in pivoting and cutting sports, a 2-year prospective study was performed on intercollegiate athletes at a Division I university. Daily practice times and athlete participation in practices and games were recorded for each sport during the 2-year period. Bilateral intercondylar notch view radiographs were taken of all athletes enrolled in the study. The notch width index, a ratio that measures the width of the anterior outlet of the intercondylar notch divided by the total condylar width at the level of the popliteal groove, was measured for each knee. A total of 213 athletes, representing 415 anterior cruciate ligament-intact knees, were enrolled in the study. There were 7 anterior cruciate ligament tears. Statistical analysis demonstrated a correlation between femoral intercondylar notch stenosis and anterior cruciate ligament injuries. No statistical difference was found between the sex of the athlete and notch width indices or rate of anterior cruciate ligament tears. Athletes with intercondylar notch stenosis appear to be at increased risk for noncontact anterior cruciate ligament injuries. PMID- 8198188 TI - Measurements of the intercondylar notch by plain film radiography and magnetic resonance imaging. AB - The purpose of this investigation was twofold. In Part I, we determined the accuracy of morphometric analysis of the knee using magnetic resonance imaging and plain film radiography. The results of Part I validated the accuracy of magnetic resonance measurements and its superiority over plain film measurements. In Part II, we evaluated knee morphometry in 20 asymptomatic athletes with chronic anterior cruciate ligament insufficiency to determine if any predisposing factors to anterior cruciate ligament disruption could be detected. With our analysis, we could detect no predisposing factors to explain the anterior cruciate ligament disruption in the cohort group. PMID- 8198189 TI - Patellar tendon versus doubled semitendinosus and gracilis tendons for anterior cruciate ligament reconstruction. AB - The results of intraarticular anterior cruciate ligament reconstruction with either the patellar tendon or the semitendinosus and gracilis tendons (four strands) were prospectively compared in a consecutive series of 60 patients with chronic injuries. A single surgeon performed arthroscopically assisted reconstructions in an alternating sequence. Preoperative and operative data revealed no significant differences between the two groups. After 28 months of followup there were no significant differences in the incidence of symptoms, and recurrent giving way was present in only one knee with semitendinosus and gracilis tendon graft. Return to sport participation was more frequent in the patellar tendon group (80% versus 43%, P < 0.01). A minor extension loss (< or = 3 degrees) was more frequent in the patellar tendon group (47% versus 3%, P < 0.001). Other differences between the two groups were not significant. KT-2000 arthrometer side-to-side difference of anterior displacement > 5 mm at 30 pounds was present in 13% of the knees with patellar tendon grafts and in 20% of those with semitendinosus and gracilis; a patellofemoral crepitation developed in 17% and 3% of the two groups, respectively. Based on these data we routinely use patellar tendon grafts. Semitendinosus and gracilis tendons are preferred in selected cases: older patients, patients with preexisting patellofemoral problems, and those with failed patellar tendon grafts. PMID- 8198190 TI - The prevalence of gonarthrosis and its relation to meniscectomy in former soccer players. AB - The prevalence of radiographic signs of gonarthrosis and its relation to knee injuries were studied in 286 former soccer players--215 nonelite and 71 elite players--and were compared with 572 age-matched controls with a mean age of 55 years. The prevalence of gonarthrosis among the nonelite players was 4.2%, among the elite players 15.5%, and among the controls 1.6%. Seven of the soccer players had known anterior cruciate ligament injuries, and 40 had had meniscectomies. Of the 32 nonelite players with knee injuries, 4 (13%) had gonarthrosis, and of the 183 without known knee injuries 5 (3%) had gonarthrosis. Among the elite players, the prevalence of gonarthrosis in knees without diagnosed injuries was 11%. We conclude that soccer, especially at an advanced level, is associated with an increased risk for gonarthrosis. After excluding subjects with known knee injuries, there was no difference between nonelite players and controls, but we found a higher rate of gonarthrosis among the elite players. PMID- 8198191 TI - Effect of an ankle orthosis and ankle ligament anesthesia on ankle joint proprioception. AB - The purposes of this study were to determine the effect of a rigid ankle orthosis (Aircast Air-Stirrup) and lateral ankle ligament anesthesia on ankle joint proprioception. Twelve noninjured subjects attempted to match nine reference ankle joint positions with their eyes closed before and after application of the ankle brace and before and after one or two of the lateral ankle ligaments (anterior talofibular and calcaneofibular) were anesthetized. Three-dimensional ankle joint orientations were recorded with a Motion Analysis system. No significant differences in the constant, variable, or absolute error were seen between subjects in the non-anesthetized and anesthetized conditions (P > 0.05), regardless of whether one or two ligaments were anesthetized. Thus, it appears that ligament mechanoreceptors contributed little to ankle joint proprioception, and that the afferent feedback from skin, muscle, and other joint receptors was adequate for the positioning task of the present study. Both the variable and absolute error in matching the reference positions were significantly less with the orthosis than without (P < 0.05). Application of an orthosis may increase the afferent feedback from cutaneous receptors in the foot and shank, which may in turn lead to an improved ankle joint position sense. PMID- 8198192 TI - Arthroscopic treatment of posttraumatic elbow pain and stiffness. AB - Nineteen consecutive cases of posttraumatic arthrofibrosis of the elbow secondary to a fracture or fracture-dislocation and treated with arthroscopic debridement and manipulation were retrospectively reviewed. All of the patients had pain and stiffness in their elbows, and all had failed a conservative therapy program. All 19 patients were followed postoperatively for an average of 29 months (range, 12 to 51). One hundred-point scoring systems were used to evaluate subjective (pain, swelling, locking, and activities) and objective (range of motion) results. The average preoperative subjective score of 39 improved to 91 postoperatively (P = 0.0001); the objective score improved from 46 preoperatively to 81 postoperatively (P = 0.0001). Extension improved from a mean of 29 degrees to 11 degrees; flexion improved from an average of 123 degrees to 134 degrees. Fourteen patients had limitations in their sports activity preoperatively; 11 were able to return to their preinjury levels of activity after surgery. This study demonstrated good-to-excellent overall results in 79% of the patients treated with arthroscopic debridement for posttraumatic elbow arthrofibrosis. Although complete return of preinjury motion was not obtained, each patient showed a significant improvement in motion and subjective symptoms. PMID- 8198193 TI - The development of suture anchors for use in soft tissue fixation to bone. AB - Soft tissue fixation to bone is a basic technique of orthopaedic surgery for which a multitude of devices have been developed. A new class of orthopaedic devices termed "suture anchors" has been developed to secure soft tissues to bone using suture material. The suture anchor is designed to allow quick and secure fixation without the need for extensive exposure. This device was tested using in vitro and in vivo models and found to be comparable with standard transosseous and two-pronged stable techniques. This device should prove useful in allowing the versatility of suture fixation of soft tissues to bone without the technical requirements of constructing transosseous suture tunnels. PMID- 8198194 TI - Anterior cruciate ligament graft fixation. Comparison of hamstring and patellar tendon grafts. AB - This study assessed the tensile properties of hamstring and patellar tendon anterior cruciate ligament reconstructions in older cadaveric knees (age range, 48 to 79 years). Mechanical testing to failure was conducted by translating the tibia anteriorly at 1 mm/sec with the knee in 20 degrees of flexion. The strongest gracilis-semitendinosus graft fixation technique (103% of intact anterior cruciate ligament) had the tendons doubled and secured with soft tissue washers (P < 0.01). However, all reconstructions using gracilis-semitendinosus grafts were significantly less stiff than the intact anterior cruciate ligament specimens regardless of fixation technique (P < 0.01). The highest strength patellar tendon graft fixation technique (84% of intact anterior cruciate ligament) was obtained with a combination interference screw and suture technique. The difference in stiffness between a patellar tendon graft and an intact anterior cruciate ligament was not significant when interference screws were placed at both ends of the graft (P > 0.05). Both types of grafts failed most often on the tibial side. With appropriate fixation, both grafts approximated the intact anterior cruciate ligament in strength, but only patellar tendon grafts secured with interference screws were comparable in stiffness. PMID- 8198195 TI - Stress fractures of the femoral shaft in athletes--more common than expected. A new clinical test. AB - Athletes from 20 Division I AA collegiate varsity sports and 1 club sport were followed carefully for the development of stress fractures during the 1990 to 1991 and the 1991 to 1992 academic years. During this period, among 914 athletes, 34 stress fractures were sustained. Seven of these, or 20.6%, were of the femoral shaft. This represents a much higher incidence than previously observed in athletes. A new clinical test is described that significantly aids in the early diagnosis and follow-up treatment of femoral shaft stress fractures. PMID- 8198196 TI - Identification of a threshold for skeletal muscle injury. AB - This study was designed to detect the first evidence of injury to muscle induced by passive stretching. Rabbit extensor digitorum longus and tibialis anterior skeletal muscles were subjected to passive stretching at set force levels of 20% or 30% of load to failure. Both tibialis anterior and extensor digitorum longus muscles that were stretched to 30% exhibited no difference in the three tensile parameters when compared with their contralateral control specimens. Maximum contractile force was decreased after stretching. Tibialis anterior and extensor digitorum muscles that were stretched to 20% of control failure force showed no decrement in the tensile parameters or maximum contractile force. Histology of the extensor digitorum longus muscles stretched to 30% of failure force showed small focal areas of muscle fiber rupture and hemorrhage near the distal myotendinous junction. Tibialis anterior and extensor digitorum longus muscle tendon units stretched to 30% of failure force suffered functional injury as their contractile ability decreased after stretching. In contrast, muscle-tendon units stretched to 20% of failure force suffered no decrement in contractile ability; therefore, a threshold for passive muscle stretch injury has been found. Furthermore, changes in contractile properties and histologic assessment appear to be more sensitive predictors of injury than measurement of structural failure properties. PMID- 8198197 TI - Hamstring injuries in sprinters. The role of concentric and eccentric hamstring muscle strength and flexibility. AB - Eleven sprinters with recent hamstring injuries were compared with nine uninjured runners. The flexibility of the hamstrings and the eccentric and concentric muscle torque were measured in the hamstrings and quadriceps muscles at different angular velocities. Sprinters with a previous hamstring injury had significantly tighter hamstrings than uninjured sprinters had. The uninjured sprinters had significantly higher eccentric hamstring torques at all angular velocities. They also had significantly higher concentric quadriceps and hamstring torques at 30 deg/sec but not at higher velocities. Sprinters with a history of hamstring injury thus differed from uninjured runners, being weaker in eccentric contractions and in concentric contractions at low velocities. PMID- 8198198 TI - Atraumatic osteolysis of the distal clavicle. Results of open surgical excision. AB - A group of 14 patients underwent 17 consecutive open surgical excisions of the distal clavicle for atraumatic osteolysis after having failed conservative treatment. All patients were men involved in weight training or heavy-lifting occupations. The diagnosis was based on no history of shoulder trauma, positive plain radiographs, and positive joint scintigraphy. All 14 patients were available for followup at an average of 25 months postoperatively. The UCLA Shoulder Rating Scale was used for evaluation. All patients reported full return to sports and employment at a satisfactory level. All results were rated as excellent (8) or good (9). Eleven of the 14 patients had bilateral involvement to some extent. One patient had undergone open excision of the contralateral distal clavicle before the study and 3 patients presented with bilateral symptoms and underwent staged bilateral excisions during the study. Seven patients presented with contralateral symptoms and radiographic involvement at latest followup after return to weight-lifting activities. PMID- 8198199 TI - Electromyographic analysis of hip and knee musculature during running. AB - The purpose of this study was to describe the firing pattern of 11 hip and knee muscles during running. Thirty recreational runners volunteered to run at 3 different paces with indwelling electromyographic electrodes while being filmed at 100 frames per second. Results demonstrated that medial and lateral vasti muscles acted together for knee extension during terminal swing and loading response, possibly providing a patella stabilizing role. The vastus intermedius muscle functioned with the other vasti, plus eccentrically controlled knee flexion during swing phase. The rectus femoris muscle fired with the vastus intermedius muscle and assisted the iliacus muscle with hip flexion. The hamstrings fired primarily to eccentrically control hip flexion. The adductor magnus, tensor fascia lata, and gluteus maximus muscles afforded pelvic stabilization while assisting with hip flexion and extension. Forward propulsion was provided mainly by hip flexion and knee extension, which is contrary to the view that posterior calf muscles provide propulsion during toe off. Faster running paces lead to increased activity in the muscles. This may lead to more injuries, primarily in the muscles that were contracting eccentrically. PMID- 8198200 TI - Healing characteristics of a type I collagenous structure treated with corticosteroids. AB - One hundred twenty-eight skeletally mature New Zealand White rabbits were used to study the effect of a single corticosteroid injection on the biomechanical, biochemical, and histologic aspects of ligamentous healing. Two steroid dosages were used. The amount of the low-dose steroid was calculated by determining the corticosteroid concentration at which fibroblastic synthesis of collagen was inhibited in vitro. A human equivalent dose of betamethasone was used as the high dose steroid injection. These two steroid doses and a saline control were injected around a transected medial collateral ligament. At 10 days all groups showed significantly inferior biomechanical properties relative to noninjected controls. By 3 weeks the human equivalent steroid dose group continued to demonstrate significantly inferior properties. Histologic and biochemical analyses confirmed the biomechanical results. The clinical relevance of the study was that the delivery of a human equivalent steroid dose into an acutely injured ligament significantly impairs the healing process relative to a noninjected ligament at 10 days and at 3 weeks after injury. This implies that a corticosteroid-treated injured ligament may not be able to withstand the mechanical loads of early vigorous rehabilitation. PMID- 8198201 TI - The anterior cruciate ligament in controlling axial rotation. An evaluation of its effect. AB - Changes in axial tibial rotation after anterior cruciate ligament sectioning were evaluated in 14 fresh human knee joints. Simulation of vertical stance in a quadriceps-stabilized knee was performed. Internal and external rotational torques were applied before and after anterior cruciate ligament sectioning. Pivot shift tests were done in the intact and anterior cruciate ligament sectioned knee. Results of pivot shift tests were all negative before sectioning and positive after isolated sectioning. No significant change in axial rotation occurred between the intact and sectioned knee for external rotation (P = 0.24) or internal rotation (P = 0.12). Presence of a load at the femoral housing in both the intact and ligament-sectioned knees caused a significant change in external rotation (P < 0.0001). No significant change was noted in internal rotation between loaded and unloaded states (P = 0.70). Total tibial rotation in the intact knee was noted to vary between 31 degrees at 0 degree of flexion and 42 degrees at 60 degrees of flexion. These results suggest that the anterior cruciate ligament does not play a significant role in limiting axial rotation and that rotational instability is not a major factor after isolated anterior cruciate ligament rupture. PMID- 8198202 TI - Instrumented arthrometry for diagnosing partial versus complete anterior cruciate ligament tears. AB - Nineteen patients with the clinical diagnosis of anterior cruciate ligament injury were examined by KT-1000 arthrometry before arthroscopy in an effort to differentiate partial from complete tears. To this end, the KT-1000 arthrometer was equipped with a strain gauge and processor that permitted the required force to increase the anterior displacement by 1-mm increments, to be read on a light emitting diode. The measured force has been plotted against anterior displacement expressed in non-linear increments along the x-axis to allow for the viscoelastic nature of the ligament. The results show that stress-strain diagrams of partially torn and completely torn ligaments are similar to those obtained by graded stress radiography. Using arthroscopy as the standard of measurement, partial tears can be differentiated from complete tears with a sensitivity of 80% and a specificity of 100%. The figures for complete tears versus partial tears are 100% and 80%, respectively. Graded arthrometry with x-y recording of the force-displacement relationship that allows for the viscoelastic qualities of ligament further extends the capabilities of instrumented arthrometry. PMID- 8198203 TI - Alteration of copolymer-specific humoral and cell-mediated immune responses by ethanol. AB - Excessive alcohol consumption represents a major human health threat. The frequency and severity of infections in alcoholics is often pronounced, suggesting impaired immune function in these patients. The precise effect of ethanol on cells of the immune system is poorly understood. We have previously shown that synthetic copolymers of L-amino acids, GT and GAT, are powerful tools for clarifying the role of regulatory T-cells in both cell-mediated and humoral immunity in inbred mouse strains. We asked whether these same antigens would have application to a murine model of ethanol consumption. In this study, female mice were placed on a nutritionally complete liquid diet containing 35% ethanol derived calories. As control, mice either were placed on a liquid control diet that isocalorically substitutes sucrose for ethanol or remained on a solid diet consisting of standard laboratory chow and water ad libitum. Our data show that the liquid ethanol diet severely inhibits two measures of cell-mediated immunity, the ability of responder B6 mice to make an anti-GAT delayed hypersensitivity and GAT-specific T-cell proliferative responses as compared with pair-fed liquid control diet or solid diet controls. On the contrary, this liquid ethanol diet does not significantly impair humoral immunity; it allows nonresponder C57BL/6 or C3H/HeN mice to respond in vivo to GT immunization. These findings suggested to us that the effect of ethanol may occur prior to antigenic stimulation, and this was confirmed by in vitro immunization. PMID- 8198204 TI - Alcohol and platelet function. AB - Epidemiological studies have shown that moderate consumption of alcoholic beverages is inversely related to the incidence of the complications of coronary artery disease. The protective effect of ethanol may be partially attributable to an inhibitory effect of ethanol on platelets. This article summarizes the experimental observations that ethanol inhibits platelet responses to specific physiological agonists. In alcoholics, various platelet defects have been observed, but these may be influenced by metabolic factors rather than the presence of ethanol alone. The acute effects of ethanol on platelet functions both in vivo and ex vivo will be reviewed. Evidence will be presented demonstrating that ethanol added acutely in vitro inhibits phospholipase A2 in stimulated platelets. The interaction of ethanol with other signal transduction pathways will also be discussed. PMID- 8198205 TI - Alcoholic cardiomyopathy. AB - Chronic alcoholism is one of the most important causes of dilated cardiomyopathy, and a large proportion of chronic alcoholics demonstrate impairment of cardiac function. The development of cardiac dysfunction is apparently related to the total lifetime dose of ethanol. Studies in experimental animals have demonstrated that both acute and chronic ethanol administration impair cardiac contractility. However, the relationship, if any, between the acute effects of alcohol and the development of irreversible cardiomyopathy remain to be elucidated. PMID- 8198206 TI - Structure and function of G proteins mediating signal transduction pathways in the heart. PMID- 8198207 TI - Flow cytometric analysis of lymphocyte subsets of mice maintained on an ethanol containing liquid diet. AB - Alcoholic patients often have impaired immune function, yet little is known about the precise mechanism(s) of this impairment. We have previously shown that ethanol consumption by mice alters copolymer-specific humoral and cellular immune responses. In this study, we asked whether alcohol consumption by mice would phenotypically alter lymphocyte populations. Female C57BL/6 mice were fed a nutritionally complete liquid diet containing 35% ethanol-derived calories for up to 8 days. As controls, mice either were fed a liquid control diet that isocalorically substitutes sucrose for ethanol or remained on a standard solid diet and water ad libitum. Although mice fed ethanol-containing liquid or pair fed control liquid diets have decreased numbers of spleen cells compared with solid diet controls, only the ethanol-containing diet allowed normally nonresponder C57BL/6 spleen cells to make antibody responses to the poly(Glu50Tyr50) synthetic copolymer antigen. Flow cytometric analysis of splenic lymphocyte populations of mice on the ethanol-containing diet shows an increase in the relative proportion of T-lymphocytes as compared with mice on either solid or liquid control diets. No such change is seen for either B-cell or natural killer cell populations in these same mice. Both liquid control and liquid ethanol diets caused a slight decrease in the CD4:CD8 ratios of splenic T lymphocytes. We see the relative percentage of T-cells bearing the alpha beta T cell receptor (TcR) increases in the spleens of liquid ethanol diet mice; a smaller increase TcR alpha beta usage is seen in the spleens of liquid control mice, compared with solid diet mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198208 TI - Effects of ethanol on the contractile function of the heart: a review. AB - Chronic ethanol consumption leads to a number of alterations in the contractile function of the heart and is a leading cause of cardiomyopathy. Ethanol also has an acute negative inotropic effect mediated by direct interaction with cardiac muscle cells, although this action is often masked by indirect actions resulting from enhanced release of catecholamines in vivo. This article reviews the effects of ethanol on the contractile function of the heart. The specific targets affected by ethanol in cardiac muscle cells are discussed in terms of potential mechanisms underlying the depressions of contractility resulting from both acute and chronic actions of ethanol. PMID- 8198209 TI - Alcoholism and myocardial energy metabolism. AB - A review of the effects of chronic ethanol consumption on myocardial energy metabolism in animal models reveals that alterations in cardiac function are not accompanied by changes in the levels of the high-energy metabolites, ATP, and creatine phosphate. There are minor alterations in mitochondrial ultrastructure and function that appear to be accentuated by lowered nutrient intake. Observations to date indicate that, in animal models, there is an interaction between chronic ethanol consumption and caloric deprivation in eliciting alterations in myocardial energy metabolism. Furthermore, ethanol-related ultrastructural changes and depressed mitochondrial function are much more demonstrable in liver than in heart, suggesting strongly that the myocardium is less susceptible to the deleterious effects of alcohol than is the liver. PMID- 8198210 TI - Smooth muscle: excitation-contraction coupling, contractile regulation, and the cross-bridge cycle. PMID- 8198211 TI - Acetate-mediated effects of ethanol. AB - Ethanol has been shown to increase markedly portal blood flow, primarily by increasing intestinal blood flow. This effect of ethanol is reproduced by acetate, infused at rates equivalent to those leading to endogenous acetate production following ethanol administration. The physiological mediator, adenosine, is also known to increase markedly intestinal and portal tributary blood flow. We have shown that adenosine receptor blockade with 8 phenyltheophylline completely abolishes the effects of ethanol, acetate, and adenosine on intestinal and portal blood flow, suggesting that increases in adenosine tone may constitute a common mechanism mediating the actions of both ethanol and acetate on the splanchnic vasculature. Studies are also presented that show that acetate administration has marked effects on central nervous system function. On two tests, motor coordination and anesthetic potency, both ethanol and acetate showed similar effects. The effects of acetate were fully abolished by 8-phenyltheophylline. The effects of ethanol were partially blocked by 8-phenyltheophylline, with a greater effect of this blocker being seen at low doses of alcohol. Whereas ethanol at low doses increased locomotor activity in mice, acetate markedly reduced it. The effect of acetate on locomotion was fully reversed by the adenosine receptor blocker 8-phenyltheophylline, whereas the activating effect of ethanol on locomotion was markedly enhanced by this blocker. These data suggest that the actions of ethanol on locomotor activity normally result from the combination of a direct stimulatory effect of ethanol per se and an inhibitory effect of acetate, produced endogenously from ethanol. When the latter effect of acetate is abolished by adenosine receptor blockade, the activating effect of ethanol is fully expressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198212 TI - An examination of the alcohol consumption and peptic ulcer association--results of a national survey. AB - Excessive alcohol consumption causes damages to the stomach or duodenum by impairing the integrity of the mucosal barrier. The aim of this study was to estimate the association between alcohol consumption and peptic ulcer, utilizing a large representative sample of the U.S. population, while controlling for cigarette smoking and major sociodemographic variables. Results indicated that alcohol consumption only minimally increased the odds of peptic ulcer. Thus, this study offers little support for the association between ethanol intake and peptic ulcer. PMID- 8198213 TI - Sleepiness and ethanol effects on simulated driving. AB - Twelve healthy young men were assessed in each of four experimental conditions presented in a Latin Square design: 8-hr time in bed (TIB) and placebo, 4-hr TIB and placebo, 8-hr TIB and ethanol, and 4-hr TIB and ethanol. After consuming ethanol (0.6 g/kg) or placebo (0900-0930 hr) with 20% supplements at 1030 and 1100 hr, subjects were tested for sleepiness (Multiple Sleep Latency Test at 1000, 1200, 1400, and 1600 hr) and divided attention (1030 hr) performance on day 1, and for simulated driving and divided attention (1000-1200 and 1400-1600 hr) performance on day 2. In the morning testing, with breath ethanol concentrations (BECs) averaging 0.049%, sleepiness was increased, divided attention reaction times increased (on both days), and simulated driving performance was disturbed in the ethanol and 4-hr TIB relative to placebo. Similarly in the afternoon, with BECs averaging 0.013%, the ethanol and 4-hr TIB condition increased sleepiness and disrupted divided attention and simulated driving performance. The results show that sleepiness and low-dose ethanol combine to impair simulated automobile driving, an impairment that extends beyond the point at which BEC reaches zero. They provide a possible explanation for the incidence of alcohol-related automobile accidents at low BECs. PMID- 8198214 TI - A neuropsychologic profile of adolescent alcoholics. AB - Male and female adolescents who qualified for a DSM-III-R diagnosis of Alcohol Abuse or Dependence and a control sample of nonalcohol-abusing male and female adolescents were administered a battery of intellectual, achievement, and neuropsychologic tests. Alcohol-abusing adolescents were found to have significantly lower verbal and full-scale IQ scores than controls. Furthermore, alcohol-abusing adolescents were found to have a trend toward lower age standardized scores on achievement tests of reading ability and spelling. Surprisingly, alcohol-abusing adolescents made less perseverative errors and commission errors on a learning and memory task than controls. Control males performed worse on the Wisconsin Card Sort than alcoholic males, whereas alcohol abusing females performed worse than control females. In addition, alcoholic subjects scored better than controls on a measure of visual memory sensitivity. The results indicate that adolescent alcohol abusers in general have poorer language skills than adolescents who do not abuse alcohol. However, in contrast to results obtained from studies of adult alcoholics, there is little evidence of significant brain damage as revealed by using neuropsychologic test performance. PMID- 8198216 TI - Volumetric magnetic resonance imaging quantification of longitudinal brain changes in abstinent alcoholics. AB - Magnetic resonance imaging (MRI) of the brain was performed on a group of 24 recently detoxified, male alcoholics approximately 1 month after their date of last drink. The imaging was repeated 3 months later, at which point 9 subjects had resumed drinking and 15 had maintained abstinence. Contrasts between these two drinking groups revealed that, despite comparable baseline values, the Abstainers exhibited volumetric white matter increases and cerebrospinal fluid reductions over the follow-up interval, whereas the Drinkers did not show significant change on either of these MRI indices. These results provide the first evidence suggestive of significant volumetric white matter increase with abstinence. PMID- 8198215 TI - Detection of reduced acetaldehyde protein adducts using a unique monoclonal antibody. AB - Acetaldehyde (AA), the major product of alcohol metabolism, has been shown to bind to proteins in vivo and form chemical adducts. These AA-protein adducts have been shown to alter protein structure and function and may result in tissue damage. Recent reports have shown that polyclonal antibodies can be produced that recognize proteins modified in vitro with AA in the presence of sodium cyanoborohydride (NaCNBH3), a strong reducing (R) agent. Antibodies prepared in this way have been shown to recognize proteins in the livers of rats fed alcohol chronically. Because multiple AA-protein adducts can be recognized by polyclonal antisera, and a variety of adducts may be formed in vitro or in vivo, this study was designed to develop monoclonal antibodies specific for proteins modified by AA. In addition, adducts formed under R conditions are probably chemically different than those formed under nonreducing (NR) conditions, and monoclonal antibodies may provide the specificity required to distinguish these chemical differences. Balb/c mice were immunized with bovine brain tubulin that was modified by treatment with 5 mM AA for 7 days under NR conditions. Sera from immunized animals were tested for antibody activity to the immunogen (protein-NR) and for cross-reactivity to protein-R and unmodified protein. Although the highest serum antibody titers were seen toward the NR adduct, antibodies to the R adduct were also detected. This activity difference was independent of the carrier protein, because NR and R bovine serum albumin, keyhole limpet hemocyanin, and actin also gave similar results when used as the adducted protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198217 TI - Ethanol effects on embryonic craniofacial growth and development: implications for study of the fetal alcohol syndrome. AB - Fetal alcohol syndrome (FAS), which is brought about by maternal consumption of ethanol during pregnancy, is a major public health problem. To gain understanding of the etiology of this condition, a number of teratological studies have been performed in different animal systems to develop an animal model for FAS. The C57BL/6J mouse strain has been described as susceptible to the teratogenic effects of ethanol, whereas the ICR (CD-1) strain is considered relatively insensitive. We have compared the effects of ethanol on DNA and protein synthesis in cultured embryonic palate mesenchymal cells from both strains to determine if the reported differential sensitivity to ethanol is reflected in differences in ethanol's effects on cell behavior. Chronic exposure to 200 mM ethanol for 48 hr had a strong inhibitory effect on DNA synthesis in palate cells derived from both the C57BL/6J and ICR strains and a significant effect on protein synthesis in C57BL/6J palate cells. When we attempted to verify strain differences in susceptibility to ethanol teratogenesis, we were not able to observe an increased incidence of birth defects due to ethanol in either strain. High doses of ethanol (5.8 g/kg, administered by intraperitoneal injection on gestational day 8) resulted in death in both C57BL/6J and ICR mice. A lower dose (4.8 g/kg) caused decreased fetal weight and increased resorption in both strains, but did not bring about FAS-like craniofacial dysmorphology in either strain. It appears, therefore, that whereas ethanol can significantly affect the behavior of cells derived from craniofacial tissue, these effects cannot be correlated with sensitivity to ethanol teratogenesis in the mouse system. PMID- 8198218 TI - Statistical approaches in alcohol research: a comparative survey of two major alcohol journals with four major psychiatric journals. AB - This study surveyed and compared the statistical methods used in two major alcohol journals with those used in four major psychiatric journals. The alcohol specialty journals were Alcoholism: Clinical and Experimental Research and Journal of Studies on Alcohol. The psychiatry journals studied were the American Journal of Psychiatry, British Journal of Psychiatry, Archives of General Psychiatry, and Acta Psychiatrica Scandinavica. The aim of this study was to examine the extent to which alcohol researchers use statistical methods and their level of statistical sophistication. A second aim focused on the extent to which alcohol researchers are attentive to design and sample size issues. Comparisons between papers published in the four psychiatry journals and the two alcohol specialty journals published in 1990 revealed that the percentage of articles without any numerical results was substantially different among the journals: 21% of the psychiatry journals and 7% in the alcohol journals. There was a significant difference in favor of the alcohol journals with respect to frequency of intermediate statistical techniques. The number of papers published in the two alcohol journals using 20 or fewer subjects was similar to the four psychiatric journals. However, the alcohol journals contained more articles in which > 400 subjects were studied. PMID- 8198219 TI - Mortality rates and predictors of mortality among late-middle-aged and older substance abuse patients. AB - This study describes mortality rates and predictors of mortality among late middle-aged and older (55+) substance abuse inpatients (n = 21,139) in Department of Veterans Affairs (VA) Medical Centers in the 4 years after an index episode of care. A total of 24% of the patients died; this mortality rate was 2.64 times higher than expected. Predictors of earlier mortality included older age and nonmarried status, alcohol psychosis and organic brain disorder diagnoses, and several medical diagnoses, including neoplasms, liver cirrhosis, respiratory, endocrine and metabolic, and blood system disorders. Three proxy indicators of illness severity also predicted mortality: more prior inpatient and outpatient medical care and an index episode in an extended care unit. In contrast, more prior outpatient mental health care and remitted status predicted lower mortality. These diagnostic and treatment indicators can be used to identify patients at heightened risk for premature mortality. Moreover, they show that intensive mental health aftercare and remission of substance abuse may delay mortality, even among older patients who have longstanding substance abuse problems. PMID- 8198220 TI - Severity and treatment of alcohol withdrawal in elderly versus younger patients. AB - We conducted a retrospective chart review of older (n = 48; mean age = 69) and younger (n = 36; mean age = 30) patients who were admitted to residential/inpatient treatment for alcohol withdrawal and dependence. Although the two age groups did not differ in terms of recent drinking history, the elderly group had significantly more withdrawal symptoms for a longer duration than the younger group. The elderly group also had more symptoms of cognitive impairment, daytime sleepiness, weakness, and high blood pressure. Finally, no significant differences were found between age groups in either the dosage or number of days of detoxification medication, although a trend was found for more days of medication in the elderly. We conclude that alcohol withdrawal may be more severe in elderly than in younger persons. Accordingly, treatment may take longer and should target the specific profile of symptoms that characterize alcohol withdrawal in the elderly. PMID- 8198221 TI - Maternal drinking during pregnancy: attention and short-term memory in 14-year old offspring--a longitudinal prospective study. AB - A large and compelling experimental literature has documented the adverse impact of prenatal alcohol exposure on the developing brain of the offspring. This is the first report of adolescent attention/memory performance and its relationship with prenatal alcohol exposure in a population-based, longitudinal, prospective study (n = 462) involving substantial covariate control and "blind" examiners. Prenatal alcohol exposure was significantly related to attention/memory deficits in a dose-dependent fashion. A latent variable reflecting 13 measures of maternal drinking was correlated 0.26 with a latent variable representing 52 scores from 6 tests measuring various components of attention and short-term memory performance. The number of drinks/occasion was the strongest alcohol predictor. Fluctuating attentional states, problems with response inhibition, and spatial learning showed the strongest association with prenatal alcohol exposure. A latent variable reflecting the pattern of attention/memory deficits observed at 14 years correlated 0.67 with a composite pattern of deficits previously detected on neurobehavioral tests administered during the first 7 years of life. The 14 year attention/memory deficits observed in the present study appear to be the adolescent sequelae of deficits observed earlier in development. As is usual in such studies, not all exposed offspring showed deficits. PMID- 8198222 TI - Effect of postnatal ethanol exposure on expression of differentiation antigens of murine splenic lymphocytes. AB - Ethanol is a recognized immunosuppressive agent in the chronic alcoholic. However, the effects of ethanol exposure on the developing immune system have not been extensively investigated. This study evaluated the effects of early postnatal ethanol exposure, via breast milk, on splenic lymphocyte differentiation antigen expression in offspring reared by ethanol-fed mice. Maternal mice were fed a liquid diet containing 20% ethanol-derived calories during pregnancy (E-P), pregnancy and lactation (E-PL), or lactation (E-L). Ad libitum-fed (C) and pair-fed (PF) control groups, fed a control liquid diet, were included. Expression of differentiation antigens on splenic lymphocytes from 21 day-old offspring reared by females in 1 of the 3 ethanol exposure conditions was evaluated by flow cytometry. Offspring reared by E-P females had similar numbers of splenic lymphocytes as offspring reared by C and pair-fed during pregnancy (PF P) females. In contrast, offspring reared by E-PL and E-L females had fewer splenic lymphocytes than both PF-PL and PF-L (respectively), and C offspring. The number of Thy 1.2+, CD4+, CD8+, and IgG+ (B-cell) splenic lymphocytes was reduced in E-PL and E-L offspring compared with PF and C offspring. E-P offspring had fewer CD4+ and IgG+ splenic lymphocytes than C, but not PF-P, offspring. The percentage of Thy 1.2+ splenic lymphocytes was significantly reduced among E-PL and E-L offspring compared with PF-PL and PF-L (respectively), and C offspring.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198223 TI - Effects of alcohol on blastocyst implantation and fecundity in the rat. AB - The effects of alcohol on blastocyst implantation and fecundity were determined. Pregnant rats (insemination = day 1) received vehicle only (water), or alcohol (2 or 4 g/kg body weight) daily by feeding tube on days 1-4 and the time of implantation determined on day 5 or fecundity assessed on day 19. Implantation sites were rendered visible by the blue-reaction; fecundity was expressed as the ratio of live fetuses to total implantations. The time course of blastocyst implantation was advanced by alcohol (2 g/kg dose). At 1000 hr, 1.9 vs. 0.9 blastocysts had implanted in treated vs. controls. By 1200 hr, 66 vs. 17% of blastocysts had implanted and by 1500 hr 90 vs. 52% had implanted in the 2 g/kg dose group vs. controls. Blastocyst implantation was not consistently advanced by the 4 g/kg dose of alcohol. The total number of blastocysts ultimately implanting did not differ between groups (control: 7.0 +/- 0.9; 2 g: 7.3 +/- 0.9; 4 g: 7.1 +/- 0.5 sites/cornu at 1800 hr). Fecundity did not differ markedly between control and the 2 g/kg dose group (97 vs. 96%, respectively), but was reduced in the 4 g/kg dose group (58%). The results indicate that daily administration of alcohol (2 g/kg body weight) during the preimplantation period (days 1-4) advances the time course of blastocyst implantation without reducing fecundity. PMID- 8198225 TI - Tolerance to ethanol hypothermia in HOT and COLD mice. AB - COLD and HOT mice have been selected to be sensitive or resistant, respectively, to the acute hypothermic effect of ethanol. Previous studies have found HOT mice to be relatively resistant to the development of tolerance to this effect, whereas COLD mice readily develop tolerance. By administering several doses of ethanol and recording multiple postdrug temperatures, in the current study we equated the selected lines for area under the curve describing initial hypothermic response over time, a measure reflecting both maximal hypothermia achieved and the duration of total hypothermic response. The dose-response function for COLD mice was much steeper than that for HOT mice, and HOT mice recovered to baseline body temperatures more slowly. Doses were administered daily for 5 days. Both lines developed tolerance to ethanol hypothermia. The magnitude of tolerance developed was greater in COLD than in HOT mice. At higher doses, HOT mice showed a progressively enhanced hypothermic response over days (i.e., sensitization). PMID- 8198224 TI - Effect of ethanol on insulin-like growth factor-II release from fetal organs. AB - This study examines the effect of ethanol (ETOH) exposure and nutrient restriction on the release of insulin-like growth factor (IGF)-II from 18- and 20 day explanted fetal organs. Fetuses were exposed to ETOH (E) in utero by feeding dams a 36% (calories derived from ETOH: 6.6% v/v) ETOH liquid diet. Control fetuses were offsprings of dams either pair-fed (P) a control liquid diet or ad libitum (A) fed a standard pelleted lab chow. Brain, heart, kidney, liver, lung, muscle, and placenta of fetuses from the same litter were pooled and explanted, and IGF-II concentration in explanted media was analyzed by radioimmunoassay. Maternal and fetal weights were determined during pregnancy and at sacrifice, respectively, to evaluate the influence of ETOH on growth. Both maternal and fetal weights were substantially reduced by ETOH on 18 and 20 days of gestation compared with both A and P controls. At 18 days of gestation, E fetuses (1.33 +/- 0.03 g) weighed less than either A (1.47 +/- 0.03 g) or P (1.54 +/- 0.04 g) fetuses. By 20 days, A mean fetal weight (4.19 +/- 0.23 g) was significantly greater than both P (3.74 +/- 0.06 g) and E (3.28 +/- 0.06 g) fetuses. IGF-II concentration in media from 18-day fetal explants was highest from E (brain, heart, liver, and placenta) and P tissues (kidney, lung, and muscle). IGF-II in media from A tissues (except placenta) was lower than both E and P levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198227 TI - Effects of ethanol on structural parameters of rat brain membranes: relationship to genetic differences in ethanol sensitivity. AB - Fluorescent probes located in different membrane regions were used to evaluate effects of ethanol (50 and 100 mM) on structural parameters (protein distribution, fluidity of total and annular lipid, and thickness of the bilayer) of synaptic plasma membranes (SPMs) from brain cortex of High-Alcohol Sensitivity (HAS) and Low-Alcohol Sensitivity (LAS) rats. An experimental procedure based on radiationless energy transfer from tryptophan of membrane proteins to pyrene, 1,3 bis-(1-pyrene)propane(pyr-C3-pyr), or 1,6-diphenyl-1,3,5-hexatriene (DPH), as well as pyr-C3-pyr monomer-eximer formation and DPH polarization, and energy transfer from pyrene monomers to 1-anilinonaphthalene-8-sulfonic acid (ANSA) was utilized. The efficiency of energy transfer from tryptophan to pyrene was sensitive to protein clustering induced in SPMs by concanavalin A. Efficiency of energy transfer from pyrene monomers to ANSA was different for vesicles of dimyristoyl phosphatidyl choline, dipalmitoyl phosphatidyl choline, and distearoyl phosphatidyl choline, consistent with differences in the thickness of these lipid bilayers. Without ethanol, there were no significant differences between the structural parameters of SPMs from HAS and from LAS rats. Addition of ethanol (50 mM) changed protein distribution (increased clustering) only in membranes from HAS rats and had no effect on the structure of membranes from LAS rats. A larger concentration of ethanol (100 mM) changed the fluidity of annular and total lipid in both lines of rats, but changed protein distribution and decreased thickness of the membranes from HAS rats with no effect on these parameters in SPMs from LAS animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198226 TI - Maternal ethanol consumption: effects on G proteins and second messengers in brain regions of offspring. AB - Previous work in this and other laboratories has demonstrated that in utero ethanol exposure adversely affects the development of the serotonergic, dopaminergic, cholinergic, and other neurotransmitter systems. In several of these systems, receptor number is significantly altered. To determine whether the altered number of two G protein-linked receptors is reflected in changes in cell function, we examined dopamine-stimulated adenylate cyclase in the striatum and cortex and carbachol-stimulated phosphoinositide (PI) hydrolysis in the cortex. Serotonin-stimulated cortical PI hydrolysis was assessed for comparison. We also studied G proteins that link adenylate cyclase and other second messenger systems to their receptors. The G proteins that were analyzed include the alpha-subunits for Gs, G0, Gi1, Gi2, and Gi3. G proteins were analyzed in the cortex and cortical regions, as well as in the brain stem. The results of these experiments demonstrated that dopamine-stimulated adenylate cyclase activity was comparable in the striatum of 5- and 19-day offspring of control and ethanol-fed rats and in the motor cortex of 19-day offspring. We also found that carbachol- and serotonin stimulated hydrolysis of cortical phosphoinositides was unchanged in ethanol exposed offspring on gestational day 19, and on postnatal days 5 and 19. G protein content was examined by Western blot analysis, using antibodies directed against the alpha-subunits of Gs, G0, and the Gi1/Gi2 and Gi3/G0 combinations. These investigations indicated that, with two minor exceptions (approximately 10% change in the proteins detected by antibodies against the alpha-subunits of the Gi1/Gi2 and Gi3/G0 combinations), there were no significant differences in the content of any of the G proteins analyzed. PMID- 8198228 TI - Ethanol consumption following acute treatment with methysergide, fluoxetine, fenfluramine, and their combination. AB - Methysergide (MS), a postsynaptic serotonin antagonist, was administered acutely in three experiments in relation to water or 5% ethanol solution intake of 24-hr, water-deprived male Sprague-Dawley rats. In the first experiment, MS significantly increased the consumption of ethanol at doses of 0.25, 2.0, and 4.0 mg/kg. Water intake was significantly increased by MS at the 2.0 mg/kg dose. In the second experiment, which was different from the first one in that MS was administered during the dark cycle, ethanol solution intake was again significantly increased at all three levels. In the third experiment, fenfluramine (FFL) and fluoxetine (FLU) were administered acutely (at 8 mg/kg) after MS (0.25 mg/kg) followed by measuring water or ethanol solution intake. FFL and FLU significantly decreased intake of both water and ethanol solution, a process that was significantly reversed by MS; to a greater degree for FLU (74%) than for FFL (57%). The successful use of MS in increasing ethanol intake in these studies may be due to the low doses used in comparison with earlier unsuccessful attempts. The procedure of treating 24-hr, water-deprived rats with acute doses of pre- and postsynaptic serotonin agonists and antagonists appears to be a useful model for further elucidation of their interaction in ethanol consummatory behavior. PMID- 8198229 TI - Influence of chronic dietary ethanol on cytokine production by murine splenocytes and thymocytes. AB - Prolonged consumption of ethanol (ETOH) results in alterations of host defense via immune modulation, increasing susceptibility to infection. In the present study, effects of chronic dietary ETOH on cytokine production by splenocytes and thymocytes, splenocyte and thymocyte proliferation induced by mitogens, splenic natural killer cell activity, and antibody production (IgA and IgG) were examined. C57BL/6 mice were fed 5% ETOH v/v in the Lieber-DeCarli liquid diet for 11 weeks. Release of interleukin (IL)-2, IL-5, IL-6, IL-10, and interferon (IFN) gamma produced by concanavalin A (Con A) stimulated splenocytes was significantly decreased, whereas secretion of IL-4 was slightly decreased by chronic dietary ETOH compared with controls. Production of tumor necrosis factor-alpha and IL-6 by lipopolysaccharide-stimulated splenocytes was significantly and slightly decreased by ETOH compared with controls, respectively. Splenocyte and thymocyte proliferation induced by Con A was significantly inhibited by ETOH, whereas splenocyte proliferation induced by lipopolysaccharide was not affected. Natural killer cell activity was significantly inhibited by ETOH compared with controls. The production of IgA and IgG by splenocytes were also significantly decreased by ETOH compared with controls. The levels of IL-2, IL-4, and IL-6 produced by Con A stimulated thymocytes were significantly reduced by dietary ETOH compared with control, whereas production of IFN-gamma by thymocytes was not affected. Our results suggest that chronic dietary ETOH alters the cytokine release, thereby impairing immune response and T-cell maturation, which increase host susceptibility to infection. PMID- 8198230 TI - Modification of lymphocyte subsets in the intestinal-associated immune system and thymus by chronic ethanol consumption. AB - Modification of the mucosa-associated intestinal immune system of female C57BL/6 mice was studied during consumption of the Lieber-DeCarli diet supplemented with 5% v/v ethanol or laboratory chow with ethanol (20% w/v) in the drinking water. All groups received ethanol for 11 weeks. Mice fed the Lieber-DeCarli diet had fewer CD8+ cells/villus than the chow-fed controls. Mice that received ethanol in the drinking water had fewer IgA-containing cells and CD8+ cells than controls. There were no differences in the number of cells in the mesenteric lymph nodes between ethanol-treated mice and their respective controls. Nevertheless, chow fed control mice had more cells than those fed the Lieber-DeCarli control diet. Although no differences were detected in the percentages of CD4+, CD8+, LECAM-1+, and LECAM-1+ CD4+ cells, there was a decrease in the percentage of LECAM-1+ CD8+ cells in ethanol-fed mice when compared with their Lieber-DeCarli controls. Mice receiving ethanol in the drinking water showed alterations in the CD4 CD45RC subsets and in the CD8 CD45RC subsets. Similar results were observed in mice receiving Lieber-DeCarli diets alone or supplemented with ethanol. The low dose, chronic exposure of dietary ethanol in the Lieber-DeCarli-fed mice did not significantly affect the numbers of various thymocyte subsets. But, a decrease in the percentage of CD4- CD8+ cells was observed in the thymus of mice receiving ethanol in the drinking water. Chronic ethanol consumption caused significant decreases in the number of CD8+ and IgA+ cells in the intestinal lamina propria, important in mucosal immune defenses. PMID- 8198231 TI - Involvement of protein kinase C in ethanol-induced inhibition of NMDA receptor function in cerebellar granule cells. AB - Ethanol inhibits N-methyl-D-aspartate (NMDA)-stimulated increases in intracellular Ca2+ in cerebellar granule cells apparently by reducing the potency of glycine to act as a co-agonist at the NMDA receptor. The inhibitory effect of ethanol on the NMDA response in these cells can be reversed not only by a high concentration of glycine, but also by the protein kinase inhibitors, staurosporine and calphostin C. We previously showed that activation of protein kinase C in cerebellar granule cells also resulted in inhibition of the NMDA response, and in decreased potency of glycine at the NMDA receptor. Furthermore, the inhibitory effects of ethanol and protein kinase C activation are not additive. These results suggest a role for protein kinase C in ethanol inhibition of NMDA responses in cerebellar granule cells. In contrast, although ethanol can inhibit the response to kainate in these cells in a "competitive" manner, this response is not affected by activation of protein kinase C. PMID- 8198232 TI - Epidemiology of coronary heart disease--influence of alcohol. PMID- 8198233 TI - Thrombosis and fibrinolysis in acute myocardial infarction. AB - The development of coronary thrombosis in response to rupture of atherosclerotic plaques is the primary determinant of the evolution of stable atherosclerotic coronary disease to unstable ischemic syndromes and acute myocardial infarction. Activation of the tissue factor pathway of coagulation and adhesion of platelets are critical events in the initiation of thrombosis. However, subsequently, other factors may determine the extent of thrombosis by modulating the intensity of procoagulant and fibrinolytic activity. Marked procoagulant activity, attenuation of physiologic fibrinolytic activity, or both appear to be risk factors for myocardial infarction. The results of recent studies have provided considerable insight into potential mechanisms for thrombosis in response to rupture of atherosclerotic plaque and have identified potential novel antithrombotic interventions to inhibit the progression of coronary thrombosis. PMID- 8198234 TI - Soluble markers of allergic inflammation. PMID- 8198236 TI - Therapeutic effect of loratadine on pruritus in patients with atopic dermatitis. A multi-crossover-designed study. AB - The aim of the study was to assess the therapeutic efficacy of loratadine on pruritus in patients with atopic dermatitis, considering the patients' sensation of itch. Sixteen patients, mean age 24.8 years, with moderate or severe atopic dermatitis were included in a double-blind and placebo-controlled study with a six-period, multi-crossover design. The patients were given 10 mg loratadine or placebo every day, alternating between loratadine and placebo every 2 weeks. The degree of pruritus during the day and during the night was recorded by the patients every morning and every evening, respectively, on a 10-cm visual analog scale. The study detected a significant effect of loratadine, as compared with placebo, on pruritus during the day, pruritus during the night, and severity of rash. At least nine of the 16 patients included were classified as responders and only one as a nonresponder to loratadine treatment. It is concluded that loratadine may be tried as an adjuvant therapy in the management of severe and moderate atopic dermatitis, in patients complaining of pruritus. PMID- 8198237 TI - Adverse reactions to food additives in children with atopic symptoms. AB - In a multicenter study conducted at four Danish hospital pediatric departments, the parents of 472 consecutive children were informed of this project to determine the incidence of intolerance of food additives among children referred to an allergy clinic with symptoms of asthma, atopic dermatitis, rhinitis, or urticaria. After a 2-week period on an additive-free diet, the children were challenged with the eliminated additives. The food additives investigated were coloring agents, preservatives, citric acid, and flavoring agents. Carbonated "lemonade" containing the dissolved additives was used for the open challenge. Two doses were used: a low dose and a 10-fold higher dose. Gelatin capsules were used for a double-blind challenge. The children were 4-15 years old, and they were attending an outpatient pediatric clinic for the first time. Of the 379 patients who entered the study, 44 were excluded and 335 were subjected to open challenge. A total of 23 children developed positive reactions after the open challenge. Sixteen of these patients accepted the double-blind challenge, and six showed a positive reaction to preservatives (atopic dermatitis, asthma, rhinitis), coloring agents (atopic dermatitis, asthma, urticaria, gastrointestinal symptoms), and citric acid (atopic dermatitis, gastrointestinal symptoms). The incidence of intolerance of food additives was 2% (6/335), as based on the double-blind challenge, and 7% (23/335), as based on the open challenge with lemonade. Children with atopic skin symptoms had a statistically increased risk of a positive reaction. This may have consequences for the future clinical investigation of children with atopic cutaneous symptoms. PMID- 8198235 TI - A double-blind, placebo-controlled study of immunotherapy with an alginate conjugated extract of Parietaria judaica in patients with Parietaria hay fever. AB - A double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of immunotherapy (IT) with a partially purified alginate-conjugated extract of Parietaria judaica (Conjuvac Parietaria, Dome/Hollister-Stier) in patients suffering from rhinoconjunctivitis caused by Parietaria pollen. Eighteen patients (10 women, 8 men, mean age 35 years) received active treatment and 17 (10 women, 7 men, mean age 42.5 years) received placebo. Actively treated patients had significantly lower nasal symptom/medication scores (running nose P = 0.0087 and sneezing P = 0.048) during the Parietaria pollen season. Significant decreases in specific skin (P < 0.01), nasal (P < 0.05), and conjunctival (P < 0.01) reactivity to the Parietaria extract and significant increases of specific IgG (P < 0.001), IgG1 (P < 0.001), and IgG4 (P < 0.001) in actively treated patients, but not in placebo, were found. IT was well tolerated, the active extract inducing five mild systemic reactions (four rhinitis and one urticaria) and placebo two (rhinitis). A significant correlation was found between low skin reactivity and high specific IgG (P = 0.0002) and IgG4 (P = 0.036). These findings indicate that IT with a partially purified P. judaica extract is an effective and safe treatment for Parietaria pollen allergy. The correlation between low immediate skin reactivity and high specific IgG and IgG4 suggests that, at least in the studied cutaneous model, these antibodies may exert a blocking effect. PMID- 8198238 TI - Booster immunotherapy (BIT). AB - This study tries to answer two questions: 1) how long does the therapeutic effect of successful immunotherapy (IT) last after termination of the treatment? and 2) what is the best treatment for recidivist patients? To answer the first question, we asked 108 patients with rye/grass pollen allergy who had previously undergone IT for 3-4 years and had responded well to treatment to complete a questionnaire on the course of their recovery after termination of the therapy. Evaluation of the answers revealed a recidivist rate of approximately 30% in the first 3 years. According to our results, the risk of a relapse after this period seems to be low. To answer the second question, we included 40 patients suffering from type I allergy to grass/rye pollen in a clinical study. Each of them had previously undergone specific IT with a grass pollen extract mixture and had terminated this therapy after 3-4 years practically free of symptoms during the grass pollen season. As the symptoms returned and increased from year to year after the end of IT, new therapeutic steps had to be considered. We investigated the efficacy of a short preseasonal injection treatment called "booster immunotherapy" (BIT). BIT was performed with two different injection-regimens, a low-dose schedule comprising six injections and a high-dose schedule with 11 injections, in both cases administered as a build-up regimen. In the next pollen season, 28/40 (70%) patients reported strong improvement or even complete remission of the allergy symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198239 TI - Plasma acetylsalicylic acid and salicylic acid levels during aspirin provocation in aspirin-sensitive subjects. AB - The ability of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit the cyclo-oxygenase which catalyzes formation of prostaglandins appears to be central to the mechanisms involved in aspirin sensitivity. We have investigated whether the plasma levels of acetylsalicylic acid (ASA) and its main metabolite salicylic acid (SA) at the time of intolerance reactions correspond with the concentrations required for enzyme inhibition in vitro. Twelve aspirin sensitive and 15 aspirin-tolerant subjects were followed during provocation with aspirin. ASA and SA concentrations in plasma were determined by HPLC. After oral provocation (up to 460 mg cumulative dose), the levels of ASA and SA in plasma were equivalent in aspirin-sensitive and aspirin-tolerant subjects. For the aspirin-sensitive subjects, at the time of adverse reaction, the concentration range was 2.9-33.3 microM for ASA and 18.1-245 microM for SA. Oral provocation with sodium salicylate yielding 10-fold higher SA levels did not elicit intolerance reactions. Statistically significantly lower levels of ASA and SA (P < or = 0.01) evoked airway obstruction, as compared with merely extrapulmonary symptoms. Bronchial absorption of aspirin was found after inhalation of lysine aspirin and was comparable in asthmatic and nonasthmatic subjects. In three aspirin-sensitive subjects who developed airway obstruction, the plasma levels for ASA and SA were 0.9-2.6 microM and 0.0-6.7 microM, respectively. In conclusion, the plasma levels of ASA reached at the time of a positive reaction are of the magnitude known to inhibit cyclo-oxygenases. Neither differences in bioavailability of ASA nor the formation of SA seems to contribute to the aspirin elicited reactions. PMID- 8198241 TI - Positivity of patch tests in cutaneous reaction to diclofenac. Two case reports. AB - Immune-mediated reactions to NSAIDs are unusual. We have observed two cases of maculopapular eruptions occurring 48-72 h after administration of diclofenac sodium. Patch tests performed with diclofenac were positive. The histopathologic findings resembled those of contact dermatitis with different degrees of dermal involvement. Clinical, allergologic, and histopathologic patterns strongly suggest a type IV mechanism of hypersensitivity. Patch tests play an important role in the assessment of possible immunologic mechanisms underlying cutaneous reactions to drugs. PMID- 8198240 TI - Identification of allergen components of the opportunistic yeast Pityrosporum orbiculare by monoclonal antibodies. AB - The yeast Pityrosporum orbiculare (P. orbiculare) is a member of the normal human cutaneous flora, but it is also associated with several clinical manifestations of the skin. We have previously observed IgE-binding components in P. orbiculare extracts, using sera from patients with atopic dermatitis. In the present study, we raised several monoclonal antibodies (MoAbs) against P. orbiculare to characterize some of its antigens, and used Candida albicans (C. albicans) as a control. We obtained several IgG1 MoAbs which specifically recognized P. orbiculare in ELISA. Two of these were selected for immunoblotting studies on P. orbiculare, and two patterns of reactivity emerged. Firstly, one MoAb showed a distinct band at a molecular mass of 67 kDa. In the second pattern, a sharp band at about 37 kDa appeared. In contrast, the IgM antibodies raised reacted with a 14-kDa component; but they reacted with C. albicans in addition to P. orbiculare. The IgG1 antibodies seemed to react with proteins, as their ability to react in ELISA with extract pretreated with protease was greatly reduced. In contrast, IgM MoAbs were much less affected, suggesting that they recognized nonprotein components. To determine whether these MoAbs-binding components were also recognized by human IgE, we adopted a radioimmunoassay (RIA) using the MoAbs as catcher antibodies. Both the 67-kDa and the 37-kDa components were IgE-binding proteins. P. orbiculare RAST positive sera were scored as positive in the RIA, whereas the control serum was not. PMID- 8198242 TI - Increased levels of blood platelet-activating factor in bronchial asthmatic patients with active symptoms. AB - Levels of platelet-activating factor (PAF) in blood from 12 bronchial asthmatic patients (six atopic and six nonatopic) were measured by radioimmunoassay after lipid extraction and separation by high-performance liquid chromatography. None of the patients were given disodium cromoglycate and prednisolone, and they were instructed to take only regular medications during the tests. Blood was drawn from the patients in a fasting state, and PAF levels were compared between the times when they were free of asthmatic symptoms and when they had mild spontaneous attacks. Ten (six atopic and four nonatopic) out of 12 patients, when they had the asthmatic attacks, showed higher levels of PAF than when they were free of the symptoms. Blood PAF levels of the patients with the active symptoms were significantly higher than those of normal healthy control subjects, suggesting that PAF may play a role in bronchial asthma. PMID- 8198243 TI - Can mite-specific IgE be used as a surrogate for mite exposure? AB - Several epidemiologic studies suggest that in mite-sensitive patients symptoms are dependent upon mite-exposure level. However, in clinical practice, it si not easy to measure major mite allergens. In contrast, assay of specific IgE antibodies can be done routinely. Thus, we wanted to compare, in a group of 40 mite-sensitive patients, the levels of mite-specific IgE (measured by RAST grade 0-6) and the level of mite group I allergen in mattresses (measured in micrograms/g house dust). The correlation coefficient between both variables was highly significant (P = 0.001). Subjects with a RAST grade of 3 or more had a 77% probability of being exposed to high (i.e., > 10 micrograms/g dust) mite allergen level. In contrast, subjects with RAST grades 0, 1, or 2 had a 77% probability of not being exposed to such high levels. Thus, measurement of serum mite-specific IgE level could be used in routine prediction of mite exposure. PMID- 8198244 TI - Chironomidae hemoglobin allergy in Japanese, Swedish, and German populations. AB - Hemoglobins of the Diptera (insect) family Chironomidae have been identified as causative allergens in asthmatic patients. In this study, 229 Japanese, 17 Taiwanese, and 92 Swedish sera from atopic patients were tested for antibodies against Chi t I, the hemoglobin from the European midge species Chironomus thummi, and against crude extracts from the Japanese midges Tokunagayusurika akamusi (T. akamusi) and Cricotopus sylvestris (Cr. sylvestris). Nearly 40% of patients showed a positive reaction to Cr. sylvestris extract, which contains no hemoglobin. This result is probably due to the presence of other partially cross reacting allergens than hemoglobin. Nearly all tested Japanese serum samples showed cross-reactivity between Chi t I and Cr. sylvestris, a finding which is evidence for common epitopes in both midge species. Furthermore, an overall good correlation between the amounts of IgE antibodies against Chi t I and Chi t I component III was found in sera from Swedish, Japanese, and German patients. PMID- 8198245 TI - Increased intestinal sugar permeability after challenge in children with cow's milk allergy or intolerance. AB - The diagnosis of cow's milk allergy or intolerance (CMAI) is based on clinical improvement on exclusion diet and relapse after challenge with milk. The aim of this work was to investigate the value of the cellobiose/mannitol (C/M) sugar permeability test, performed before and after cow's milk challenge, as a tool for the diagnosis of CMAI. Thirty-two patients underwent milk challenge at a median age of 13 months (range 3-84 months). A dual sugar (C/M) permeability test with an iso-osmolar solution was performed before and 24 h after challenge. Of the 10 patients who developed symptoms after challenge, nine showed increased postchallenge C/M ratio, whereas such an increase was observed in only one of the 22 nonrelapsed subjects. The postchallenge C/M ratio increase in relapsed subjects is to be attributed to both higher cellobiose and lower mannitol urinary excretion. These results suggest the use of the sugar permeability test, in addition to clinical observation, as an aid in the evaluation of provocation tests in infants with suspected CMAI. PMID- 8198247 TI - Baker's asthma related to soybean lecithin exposure. AB - We report two cases of soybean-lecithin-induced asthma in bakers. The patients experienced clinical symptoms in relation to an occupational exposure to this additive. Skin tests were positive with soybean lecithin, RAST showed a sensitization to soybean, and bronchial challenge tests were positive for a dilution of 10(-3) with this allergen. The same tests remained negative among healthy and asthmatic controls. Soybean lecithin, a common additive in bakery, must be added to the list of numerous aeroallergens involved in baker's asthma. PMID- 8198246 TI - A double-blind group comparative study of ophthalmic sodium cromoglycate, 2% four times daily and 4% twice daily, in the treatment of seasonal allergic conjunctivitis. AB - In a multicenter, double-blind, single-dummy, group-comparative study, 169 patients received ophthalmic sodium cromoglycate 2% four times daily, and 170 patients received 4% ophthalmic sodium cromoglycate twice daily, together with placebo eye-drops twice daily, for the treatment of seasonal allergic conjunctivitis (SAC) to birch pollen. The treatment period was 4 weeks during the birch pollen season. Daily pollen counts were used to identify the peak 14-d period. Clinical examinations were made before the start of treatment, after 1 week of treatment, and at the end of the treatment period. Patients kept daily diary record cards of eye symptom severity and concomitant therapy. Symptoms were generally mild and, except for chemosis (week 4) and soreness (weeks 2 and 3), which were less in the 4% group (P < or = 0.05), no significant treatment differences were seen for symptoms or for antihistamine rescue therapy. Both treatments were considered to be very or moderately effective by more than 90% of patients, and no treatment differences occurred in either clinicians' or patients' opinions of efficacy. The results indicate that the use of 4% sodium cromoglycate eye-drops twice daily is as effective and well tolerated as 2% sodium cromoglycate four times daily in the treatment of birch-pollen conjunctivitis. PMID- 8198248 TI - Allergen-induced expression of cell surface markers on lymphocytes of Chi t I sensitized patients. AB - Lymphocyte cultures of persons sensitized to the hemoglobin allergen Chi t I show a highly significant response to the allergen measured in the lymphocyte stimulation assay by (3H)-thymidine uptake. In this study, we investigated by flow cytometry the expression of different cell surface markers on lymphocytes after in vitro stimulation for 7 d with or without the allergen Chi t I. We determined the expression of the low-affinity receptor for IgE (CD23) on lymphocytes of Chi t I-sensitized patients and Chi t I-exposed as well as nonexposed controls. CD23 expression was significantly higher in patients than in nonexposed controls. Exposed but healthy subjects showed intermediate values. We also determined the expression of activation markers CD25 (IL-2 receptor) and HLA DR on the lymphocytes of patients and nonexposed controls. HLA-DR expression on non-T cells (CD3-) was significantly higher in patients than in controls. HLA-DR on T cells (CD3+), and CD25 as well as CD23 expression, could be significantly enhanced after antigen-specific stimulation in patients but not in controls, whereas alpha/beta-T-cell-receptor expression was significantly reduced in patients. Differences between patients and controls were not observed in response to tetanus toxoid (TT) and phytohemagglutinin (PHA). Our results demonstrate antigen-specific influences on the expression of cell surface molecules. These findings may be valuable diagnostic information. PMID- 8198249 TI - The Phadiatop test compared with RAST, with the CAP system; proposal for a third Phadiatop outcome: "inconclusive". AB - In 19 general practices, blood samples were obtained from 361 patients aged 12 years or older with chronic nasal symptoms. The Phadiatop test and a panel of RASTs to common inhalant allergens were performed on all sera with the recently introduced Pharmacia CAP system. The RAST panel was accepted as the standard. The sensitivity of the Phadiatop was 94% (95% confidence interval (CI): 89-97%), the specificity 98% (95% CI: 95-99%), the positive predictive value 97% (95% CI: 94 99%), and the negative predictive value 95% (95% CI: 91-98%). It is noteworthy that these values are very similar to those found in hospital outpatient departments. It was possible to reduce further the small percentage of false outcomes by replacing the cutoff point of the Phadiatop ratio of 1.00 by the two cutoff points 0.75 and 1.15. This resulted in three possible outcomes: a highly predictive positive outcome, a highly predictive negative outcome, and an "inconclusive" outcome. Alternatively, the cutoff point of 1.00 may be maintained while attaching the annotation "borderline" to all positive or negative Phadiatop outcomes where the Phadiatop ratio is between 0.75 and 1.15. By this simple method, physicians are alerted to the possibility of a false outcome; on the basis of the case history and other clinical findings, they can then decide whether further testing should be done. PMID- 8198250 TI - Glucocorticoid-induced attenuation of mucosal exudation of fibrinogen and bradykinins in seasonal allergic rhinitis. AB - The mucosal plasma exudate with its proteins, enzymes, derived peptides, and matrix molecules is an important factor in inflammatory airway diseases. This study investigated whether topical glucocorticosteroid treatment influences mucosal exudation of bulk plasma (fibrinogen) and the generation of plasma derived mediators (bradykinins) in seasonal allergic rhinitis. Twenty-two patients with birch-pollen-induced allergic rhinitis participated in a double blind, randomized, placebo-controlled study during the birch pollen season in 1989. After a 2-week run-in period, the participants received treatment with budesonide (200 micrograms per nasal cavity and day) or placebo. The patients kept a diary to record their daily nasal symptoms (itching, sneezing, nasal blockage, and secretion). The amount of birch pollen in the air was determined with the aid of a Burkhard pollen trap. A nasal lavage was performed once a week, and the levels of bradykinins and fibrinogen were determined in the lavage fluid samples. The birch pollen season was very mild, resulting in only minor nasal symptoms. In spite of the low pollen exposure, treatment with budesonide reduced the lavage fluid levels of both bradykinins and fibrinogen. The present results show that topical glucocorticosteroid treatment attenuates plasma exudation and the generation of plasma-derived mediators in seasonal allergic rhinitis. This action may not result from simple vascular antipermeability effects of the drug but may rather reflect the anti-inflammatory efficacy of topical glucocorticoids in the airway mucosa. PMID- 8198251 TI - Occupational asthma and rhinoconjunctivitis from inhalation of dried cow's milk caused by sensitization to alpha-lactalbumin. AB - A chocolate candy worker was diagnosed as having occupational asthma and rhinoconjunctivitis on the basis of clinical record and methacholine challenge. Positive conjunctival and bronchial challenge tests with lactalbumin showed that this protein was the pathogenetic agent. Type I hypersensitivity mechanism is demonstrated by means of skin prick test and RAST. PMID- 8198252 TI - Circulating levels of IgG1 and IgG4 anti-IgE antibodies and asthma severity. AB - In this paper, we have determined the levels of IgG1 and IgG4 anti-IgE in the sera of 66 asthma patients suffering from mild (n = 24), moderate (n = 23), or severe (n = 19) symptoms, and 20 nonatopic, healthy subjects. The study has revealed that although asthma patients have significantly elevated levels of IgG1 and IgG4 anti-IgE antibodies, the concentration of these autoantibodies is not related to the severity of asthma. This conclusion may be related to the known heterogeneity of autoanti-IgE antibodies in terms of their ability to trigger basophil histamine release. PMID- 8198253 TI - Histamine-positive skin prick testing. PMID- 8198254 TI - Biochemical characteristics of Pityrosporum allergens. PMID- 8198255 TI - Internal jugular valves: competent or incompetent? PMID- 8198256 TI - Valve injury: a new complication of internal jugular vein cannulation. AB - The anatomic appearance and competency of internal jugular valves were investigated in both cadavers and surgical patients. In 20 cadavers, the internal jugular vein (IJV) was dissected and the appearance of the valves observed. In two adult patients, the movements of the valves were observed by endoscopic visualization using an intravascular fiberscope, ultrasound techniques, and invasive venography. Transvalvular pressure gradients were measured in 10 adult surgical patients to examine the competence of the jugular venous valve. Nineteen internal jugular valves obtained from the 20 cadavers were situated directly above the termination of the IJV in the inferior bulb and were usually bilateral. The remaining 21 valves could not be examined since they had been already dissected out for another anatomical studies. The valves in 16 of the subjects were bicuspid and semiluminar. Two valves had a single cusp. The opening and closing of the valve was visualized easily with both a fiberscope and real-time ultrasound technique. Eight patients with normal central pressure had competent valves during cough-induced transvalvular pressure gradients of 45.3 +/- 10.1 (mean +/- SD) mmHg. Four valves from two cadavers remained competent at 75.4 +/- 18.2 mmHg, but became incompetent at 5.6 +/- 4.8 mmHg after a hole was made with a 14-gauge needle. Our results indicate that the IJV valve is located 0.5-2.0 cm above the union of the subclavian vein and IJV, and plays an important role in preventing retrograde blood flow to the brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198257 TI - The effects of intravenous clonidine on regional myocardial function in a canine model of regional myocardial ischemia. AB - This study was performed to investigate the effects of clonidine on regional myocardial function in a canine model of regional myocardial ischemia. Myocardial systolic shortening (%SS) was used as an index of regional myocardial function. In eight dogs after thoracotomy, the left circumflex coronary artery (LCX) was occluded by screw clamp until regional myocardial function became impaired. After partial occlusion of the LCX, cumulative doses of clonidine (1.25, 2.5, and 5.0 micrograms/kg) were administered intravenously. After administration of clonidine, heart rate, mean arterial blood pressure (MAP), and norepinephrine concentration decreased in a dose-dependent manner. At a dose of 5.0 micrograms/kg of clonidine, the LCX flow and systolic shortening of the LCX area decreased to 76% and 81% of the poststenotic values (P < 0.05, respectively), whereas no significant changes were observed at a dose of 1.25 and 2.5 micrograms/kg. These results suggest that clonidine administration and an associated decrease in arterial blood pressure deteriorates regional myocardial function of the ischemic myocardium. PMID- 8198258 TI - Tolerance to nitroglycerin in vascular smooth muscle cells: recovery and cross tolerance to sodium nitroprusside. AB - Treatment with nitric oxide (NO)-producing vasodilators such as nitroglycerin (NTG) and sodium nitroprusside (SNP) causes tolerance. Both NTG and SNP relax blood vessels by increasing guanosine 3',5'-cyclic monophosphate (cGMP) in vascular smooth muscle. We determined the effect of treatment with NTG on cGMP production in cultured pig coronary smooth muscle cells (CSM). Cells incubated for 1 h with 10 microM NTG were desensitized to the effect of NTG on cGMP, but 100 microM NTG was required to induce cross-tolerance to SNP. Acute concentration response curves of cGMP to NTG and to SNP were determined in cells pretreated for 1 h with 100 microM NTG and compared to response curves in untreated cells. In untreated cells, both NTG and SNP increased cGMP concentration dependently. SNP (1 mM) increased cGMP to 575 +/- 22 pmol/mg vs 55 +/- 4 pmol/mg for 1 mM NTG (P < 0.01, n = 8). Pretreated cells were unresponsive to acutely applied NTG but remained responsive to SNP, although the concentration-response curve to SNP was significantly depressed by approximately 60%. After washout of the NTG pretreatment, the cGMP response to SNP returned to control within 48 h while response to NTG required 72 h. These results show that smooth muscle cells exposed to NTG become tolerant to the effect of NTG on cGMP, and that cross tolerance to SNP required a 10-fold higher concentration of NTG. The cGMP concentration-response curves of these tolerant cells to rechallenge with NTG or SNP were different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198259 TI - Transtracheal Doppler cardiac output monitoring: comparison to thermodilution during noncardiac surgery. AB - The validity of transtracheal Doppler (TTD) cardiac output (CO) monitoring during noncardiac surgery has not been established. A prospective evaluation was undertaken in 30 patients undergoing noncardiac surgery to assess the agreement between TTD and thermodilution measurements of CO. Linear regression, Bland Altman analysis, and receiver operator characteristic (ROC) techniques were employed to evaluate the accuracy, reliability, and trending capability of TTD monitoring. A total of 250 simultaneous TTD and thermodilution CO values were compared. TTD and thermodilution CO measurements were highly correlated (P < 0.005, r = 0.84) and Bland-Altman analysis revealed a small systematic underestimation of thermodilution CO (mean bias = -0.25 L/min) with a SD of the bias of 0.88 L/min and a mean percent error of 12.4%. TTD performed particularly well in patients in whom the Doppler signal was stable throughout surgery and required minimal manipulation. In these patients, linear regression yielded the relation TTD CO = 0.96 thermodilution CO + 0.15 with a correlation coefficient r = 0.92. Mean percent error was 10.0% with a mean bias of -0.02 L/min and a SD of the bias of 0.58 L/min. The ability of TTD to track directional changes in thermodilution CO was evaluated by regression analysis and a ROC plot. Changes in TTD CO were highly correlated to changes in thermodilution CO (r = 0.81). ROC plots showed that changes in TTD CO reliably identified large (greater than 15%) changes in thermodilution CO with a sensitivity of 92% and a specificity of 87%. Clinical experience with the TTD device is needed to obtain accurate measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198260 TI - Role of intracellular Ca2+ pools in the effects of halothane and isoflurane on vascular smooth muscle contraction. AB - We examined the effect of halothane and isoflurane on contraction in the vascular smooth muscle of rat thoracic aorta simultaneously with the cytosolic Ca2+ levels ([Ca2+]i). Isolated spiral strips of rat thoracic aorta were suspended for isometric tension recordings in physiologic salt solution. The [Ca2+]i was measured concomitantly using fura-2-Ca2+ fluorescence. Muscle tension was elicited either by 51 mM K+ solution or 30 nM norepinephrine, and the muscle was exposed to 0%, 1%, 2%, 3% halothane or 0%, 1%, 2%, 3%, 4% isoflurane. The effects of the anesthetics were compared with the effects of verapamil, an L-type voltage dependent Ca2+ channel blocker, also administered during K(+)-induced muscle contraction. In another series, the effects of the anesthetics on caffeine- or norepinephrine-induced muscle contraction were determined in Ca(2+)-free solution. Finally, 3% halothane or 4% isoflurane was administered during K(+) induced contraction in muscle strips pretreated with ryanodine and caffeine. During K(+)-induced contraction, halothane evoked a transient increase followed by a decrease in both muscle tension and [Ca2+]i. The biphasic change in muscle tension was not elicited by isoflurane or by any agent under norepinephrine induced contraction. Both halothane and isoflurane ultimately suppressed both K(+)- and norepinephrine-induced increases in muscle tension and the [Ca2+]i in a concentration-dependent manner. The slopes of the [Ca2+]i-tension regression lines under the two anesthetics were significantly steeper than that under verapamil during K(+)-induced contraction. Halothane, but not isoflurane, augmented 4 mM caffeine-induced tension and [Ca2+]i transients in the Ca(2+)-free solution in a concentration-dependent manner. However, neither anesthetic influenced norepinephrine-induced tension and [Ca2+]i transients. In the muscle strips pretreated with ryanodine and caffeine, the difference observed between the anesthetics was abolished. In conclusion, halothane, but not isoflurane, enhances Ca2+ release predominantly from the caffeine-releasable Ca2+ stores in vascular smooth muscle; this release may modify the effect of halothane. The intracellular Ca2+ pools can be affected differently by volatile anesthetic drugs, depending on the nature of the stimulus for smooth muscle contraction. PMID- 8198261 TI - Long-term administration of pancuronium and pipecuronium in the intensive care unit. AB - This study was performed to determine the optimum dose of pancuronium (n = 30) and pipecuronium (n = 30) under continuous sedation and analgesia in the intensive care unit (ICU). This was an open clinical investigation in 60 critically ill patients with head injury, multiple trauma (in some complicated with sepsis and multi-organ failure), requiring neuromuscular block for ventilation for at least 48 h. Emphasis was placed on the neuromuscular monitoring with a peripheral nerve stimulator and adequate sedation and analgesia. Satisfactory block was achieved in all cases with an average dose of 3 mg/h with either compound. None of the patients experienced prolonged paralysis, muscle weakness, or other neuromuscular dysfunctions in the postventilatory period. We suggest that adequate use of sedative hypnotics and opioids plus neuromuscular monitoring allowed us to optimize the dose of muscle relaxants according to the need of individual patients. PMID- 8198262 TI - Sequential combined spinal epidural block versus spinal block for cesarean section: effects on maternal hypotension and neurobehavioral function of the newborn. AB - Sequential combined spinal-epidural (CSE) block was compared with spinal block for elective cesarean section. The quality of surgical analgesia and the effect on maternal blood pressure and neonatal neurobehavioral function were evaluated. Forty-two healthy parturients were randomly divided into a spinal (n = 21) and a sequential CSE (n = 21) group. A T4 sensory block was targeted. In the spinal group, 0.5% hyperbaric bupivacaine, 2.5 mL, was injected into the subarachnoid space through a 26-gauge Quincke needle. In the sequential CSE group, 1.5 mL of 0.5% hyperbaric bupivacaine was injected into the subarachnoid space through a long 26-gauge Quincke needle, which was introduced through an 18-gauge Tuohy needle. An epidural catheter was then inserted. If the block in the sequential CSE group did not reach the T4 level in 15 min, it was extended by fractionated doses of 0.5% bupivacaine administered through the epidural catheter. Ephedrine, 10 mg intravenously (i.v.), was given to treat hypotension (20% decrease from baseline value and/or systolic blood pressure below 100 mmHg). The time intervals from induction of block to start of surgery and to delivery were shorter in the spinal group (P < 0.01). Cephalad spread of block (pinprick) 15 min after induction was T4 [T2-T7] (median [range]) in the spinal group and T7 [T2-L1] in the sequential CSE group (P < 0.05). All patients in the sequential CSE group needed epidural bupivacaine, 53.8 +/- 6.5 mg (mean +/- SEM). The surgical analgesia was good or excellent in both groups before delivery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198263 TI - Intravenous administration of the proton pump inhibitor omeprazole reduces the risk of acid aspiration at emergency cesarean section. AB - This study documented gastric pH and volume, and the number of patients at risk for acid aspiration of gastric contents, in a group of mothers undergoing emergency cesarean section under general anesthesia. Patients were randomized in a double-blind fashion to receive omeprazole 40 mg intravenously or placebo at the time of decision to proceed to cesarean section. In addition, all patients received 10 mg intravenous metoclopramide and 30 mL of 0.3 M sodium citrate. Aspiration of gastric contents was undertaken immediately after endotracheal intubation (PI) and before tracheal extubation (PE). Patients with both pH < 3.5 and volume > 25 mL were deemed to be at risk of acid aspiration should regurgitation occur. Only cases where the study-drug-to-PI-aspiration interval was > 30 min were evaluated. There were 282 patients in the study group and 259 in the control group. PI, 11 patients (4.25%; 95% confidence interval [CI] 1.79 6.71) were at risk in the control group compared with 4 (1.42%; 95% CI 0.04-2.8) in the study group (P = 0.045). The omeprazole-to-PI-aspiration interval in these four cases was < or = 40 min. PE, 19 (7.3%; 95% CI 4.17-10.51) patients were at risk in the control group compared with 2 (0.7%; 95% CI 0-1.69) in the study group (P < 0.0001). Mean pH in patients receiving omeprazole was significantly higher (P < 0.001) than in the control group. Gastric volumes were significantly lower in the omeprazole group compared with the control group at both PI (P = 0.006) and PE (P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198264 TI - Epidural butorphanol does not reduce side effects from epidural morphine after cesarean birth. AB - In this prospective, double-blind, randomized study of women undergoing elective cesarean birth, the hypothesis that epidural butorphanol in various doses could effectively reduce or eliminate the side effects caused by epidural morphine was tested. Patients were randomly assigned to one of four groups. All received a standard epidural anesthetic and 20 min after delivery each received 3 mg epidural morphine with either 1 mg butorphanol (Group A), 2 mg butorphanol (Group B), 3 mg butorphanol (Group C), or 3 mL normal saline (Group D). Patient evaluations were made preoperatively and 2, 8, and 24 h after delivery. These consisted of visual analog scores for pain, satisfaction, nausea, itch, and somnolence. At each evaluation, a CO2 challenge test, using portable equipment, was performed. Data from 71 patients were analyzed and all four groups were comparable in terms of age, height, weight, level of sensory block, and volume of local anesthetic used. There were no significant differences among groups in terms of pain, satisfaction, nausea, or pruritus. Groups A, B, and C had significantly higher somnolence scores at 8 h compared to Group D (P < 0.001). There were no significant differences among groups in CO2 challenge test data at any point during the study, but overall a reduced sensitivity to CO2 after opioid administration was observed across all groups. There were no clinically significant incidents of respiratory depression. Epidural butorphanol, in doses of 1-3 mg, failed to reduce the side effects from 3 mg epidural morphine given after cesarean birth. Patients who received epidural butorphanol reported significantly higher levels of somnolence. PMID- 8198265 TI - Sodium-calcium exchange in neonatal myocardium: reversible inhibition by halothane. AB - Neonatal myocardium is distinctly more sensitive to extracellular calcium levels than is mature myocardium. This has been ascribed to the poorly developed sarcoplasmic reticulum of neonatal myocardium. Recent evidence has suggested that there is an increased dependence of neonatal myocardium on the sodium-calcium exchange current, and that sodium-calcium exchange may be a major source of calcium influx in neonatal myocardial cells. We determined the effect of halothane on the sodium-calcium exchange current on single neonatal (2- to 5-day old) rabbit ventricular myocytes by means of the whole cell voltage clamp. Lower (1.5%) halothane decreased sodium-calcium exchange current by 49%, from 29 +/- 3 to 15 +/- 6 pA. Higher (3%) halothane decreased this current by 66%, from 50 +/- 9 to 17 +/- 9 pA. Thus halothane has a reversible inhibition of sodium-calcium exchange current in neonatal myocardium. Inhibition of sodium-calcium exchange current would be expected to have a magnified effect on contractility in neonatal as opposed to adult myocardium, and could theoretically ameliorate reperfusion injury due to influx of calcium via the sodium-calcium exchanger. PMID- 8198266 TI - Epidural-morphine-induced pruritus: propofol versus naloxone. AB - In a prospective, randomized, double-blind clinical trial, we compared the efficacy of propofol and naloxone for the treatment of spinal-morphine-induced pruritus. Forty patients presenting with severe pruritus within 24 h of epidural morphine administration were allocated to receive either propofol 10 mg intravenously (i.v.) or naloxone 2 micrograms/kg. In the absence of a positive response, a second dose of the same treatment was given 5 min later. Pruritus and the level of post-operative pain were assessed every 5 min up to the end of the study period (45 min) using a verbal rating scale. The overall success rate in treating pruritus was similar in the two groups (80%). The rate of success after the first injection of the treatment drug was also similar (55%). The level of postoperative pain decreased after drug treatment in six patients (30%) in the propofol group versus none in the naloxone group (P < 0.05). Forty-five percent of the patients in the naloxone group had an increase in the level of postoperative pain versus none in the propofol group (P < 0.05). In conclusion, these results suggest that propofol and naloxone are equally effective in treating spinal-morphine-induced pruritus. However, the level of postoperative pain is significantly less in the propofol group. PMID- 8198267 TI - Epidural versus subcutaneous administration of alfentanil for the management of postoperative pain. AB - This study was designed to compare the efficacy and serum concentrations of alfentanil given subcutaneously (SQ) or epidurally (EPID) for treatment of postoperative pain. Following abdominal surgery, patients (n = 12) were randomly assigned to receive double-blind SQ or EPID alfentanil over 24 h via the allocated route (1 mg along with 0.2 mg/h and 0.2-mg boluses on demand) and saline via the other route of administration using a patient-controlled analgesic (PCA) delivery system. Significantly less EPID alfentanil produced better quality analgesia and fewer side effects than SQ alfentanil. The fact that EPID analgesia was maintained with serum alfentanil concentrations less than those producing systemic analgesia confirms the spinal site of the EPID alfentanil action. PMID- 8198268 TI - Augmentation of calf blood flow by epinephrine infusion during lumbar epidural anesthesia. AB - Lower rates of deep vein thrombosis after hip surgery performed under epidural anesthesia were noted in patients who received intravenous epinephrine infusion. To determine whether this effect could be mediated by enhanced lower extremity blood flow, 12 patients were studied immediately preoperatively. Calf blood flow increased from 3.7 +/- 1.6 to 5.0 +/- 2.2 mL.100 mL-1.min-1 with an intravenous epinephrine infusion (1.9 +/- 0.5 microgram/min). After epidural anesthesia calf blood flow increased to 6.3 +/- 3.3 mL.100 mL-1.min-1 with epinephrine infusion (2.7 +/- 1.0 micrograms/min) but was reduced to 2.6 +/- 1.5 mL.100 mL-1.min-1 when norepinephrine (0.8 +/- 0.7 microgram/min) was infused. Calf vascular resistance decreased from 27.7 +/- 13.5 to 7.9 +/- 4.6 mmHg.mL-1.100 mL-1.min-1 after epidural anesthesia with epinephrine (2.7 +/- 1.0 micrograms/min) but was unchanged when norepinephrine (0.8 +/- 0.7 microgram/min) was infused. The augmentation of lower extremity blood flow when epinephrine is used in conjunction with epidural anesthesia may in part explain the low frequency of deep vein thrombosis with conduction anesthesia. PMID- 8198269 TI - Spinal anesthesia with ropivacaine: a double-blind study on the efficacy and safety of 0.5% and 0.75% solutions in patients undergoing minor lower limb surgery. AB - The purpose of this study was to determine the clinical efficacy and safety of ropivacaine as a local anesthetic for spinal anesthesia. Forty patients between the ages of 18 and 75 yr, scheduled for minor lower limb surgery, were studied. They were randomly allocated to receive either 3 mL glucose-free 0.5% (15 mg) or 0.75% (22.5 mg) ropivacaine in a double-blind fashion. The subarachnoid puncture was performed with a 26-gauge Quincke-point needle at the L3-4 interspace with the patients in the sitting position. The onset of analgesia to pinprick was similar with both concentrations. The median (range) upper level of analgesia obtained with the 0.5% solution was T11 (L4-T5) and was T10-11 (L4-T4) with the 0.75% solution. The duration of analgesia at T12 (P < 0.01) and the total duration of analgesia (P < 0.002) were longer in the 0.75% group. In addition, the area under the number of blocked segments versus time curve was larger with the 0.75% ropivacaine solution (P < 0.001). The incidence of complete motor block of the lower limbs was higher (P < 0.02) and the total duration of motor block longer (P < 0.002) in the 0.75% group. No unexpected adverse events were registered. We conclude that subarachnoid injection of glucose-free ropivacaine solutions results in a variable spread of analgesia, mostly accompanied by a good quality of motor block, in particular with the 0.75% solution. PMID- 8198270 TI - The efficiency of an autotransfusion system for tumor cell removal from blood salvaged during cancer surgery. AB - The efficiency of a gravity-dependent autotransfusion system (ATS) for filtering tumor cells from blood was examined under laboratory and clinical conditions. In laboratory studies, reconstituted whole blood was seeded with known numbers of cultured A431 human vulva carcinoma cells then filtered through the ATS. Cancer cells were recovered from blood samples taken before and after filtration using a density gradient centrifugation procedure, and identified by immunocytochemical techniques, based upon their cytoskeletal intermediate filament proteins. It was estimated that 55%-76% of the A431 cells were retained by the ATS filters, and of those cancer cells that passed through the ATS, 62% suffered lethal trauma and the remainder showed morphologic damage. In clinical studies, blood was harvested from the surgical site during resection of primary cancers from three patients. In agreement with the laboratory studies, 50%-68% of tumor cells were filtered by the ATS from blood harvested during surgery. These results are discussed in terms of metastatic inefficiency and the potential for use of autotransfused blood salvaged during cancer surgery. PMID- 8198271 TI - Blood contamination of anesthesia equipment and monitoring equipment. AB - This study was conducted to determine the extent of blood contamination of anesthesia equipment and monitoring equipment in clinical use in operating rooms. The study employed a catalytic-test method, which is used in forensic medicine, to detect blood contamination of anesthesia equipment and monitoring equipment. Nineteen definable surfaces were sampled in 22 operating rooms. Thirty-three percent of surfaces were contaminated with blood. Contaminated equipment included surfaces that are in continuous contact with patients, e.g., blood pressure cuffs and pulse oximeter probes. Visual inspection was not a reliable means of detecting blood contamination. Whether this blood contamination represents an infection risk was not determined. Nevertheless, improved cleaning and disinfection procedures are probably needed. Equipment design needs to focus on reducing the potential for blood contamination and enhancing capability for cleaning and disinfection. PMID- 8198272 TI - A "bubble-tip" (Airguide) tracheal tube system: its effects on incidence of epistaxis and ease of tube advancement in the subglottic region during nasotracheal intubation. AB - Epistaxis and tubal obstruction in the subglottic region are difficulties encountered during nasotracheal intubation. Trauma to the nasal airway must be avoided, especially in patients receiving anticoagulant therapy. In addition, smooth passage of the tracheal tube through the larynx is desired. The tip of an Airguide tracheal tube system has a soft, round, glossy balloon head which should be less traumatic to the nasal mucosa than other more commonly used tubes. We, therefore, determined whether the Airguide reduces the incidence of epistaxis and increases smooth passage of the tracheal tube in the subglottic region during nasotracheal intubation. Sixty-six patients were divided into two groups, Airguide (n = 39) and Standard (n = 27). Each group was divided into two subgroups, topical epinephrine application as a mucosal decongestant and non epinephrine. The incidences of epistaxis and smooth passage were compared between the two groups. The Airguide group had a significantly lower incidence of epistaxis (9/39 vs 13/26; P < 0.05; bleeding was not checked in one patient in the Standard group) and provided a significantly smoother passage in the subglottic region than the Standard group (tube impingement in the subglottic region, 0/39 vs 11/27; P < 0.01). There was no significant difference in the incidence of epistaxis between the subgroups with and without topical application of epinephrine. The Airguide helps to minimize epistaxis and increases navigability in the subglottic region during nasotracheal intubation. PMID- 8198273 TI - Increased cerebral and decreased femoral artery blood flow velocities during direct laryngoscopy and tracheal intubation. AB - Direct laryngoscopy and tracheal intubation may be associated with increased heart rate, arterial blood pressure, cardiac index, and systemic vascular resistance. These responses have been attributed to sympathoadrenal stimulation. However, the studies measuring distribution of blood flow to various organs are limited. We prospectively evaluated blood flow velocities in the common carotid, middle cerebral, and femoral arteries before induction of anesthesia, after induction but before direct laryngoscopy, at the conclusion of direct laryngoscopy and tracheal intubation, and 3 min after tracheal intubation in 13 adult patients. Direct laryngoscopy and tracheal intubation produced increases in the heart rate (from 76 +/- 13 to 91 +/- 10 bpm; chi +/- SD), systolic blood pressure (from 168 +/- 20 to 206 +/- 21 mmHg), common carotid and middle cerebral blood flow velocities, but produced decreases in femoral artery blood flow velocities. Common carotid artery blood flow velocity increased from 49.4 +/- 12.5 cm/s to 65.2 +/- 20.7 cm/s (P < 0.05) at the conclusion of tracheal intubation. Middle cerebral artery blood flow velocity, which could be measured only in seven patients due to technical difficulties secondary to movement during laryngoscopy, increased from 62.4 +/- 20.5 cm/s to 78.0 +/- 27.7 cm/s (P < 0.05). In contrast, femoral artery blood flow velocity decreased from 107.6 +/- 37.8 cm/s to 76.8 +/- 28.6 cm/s (P < 0.05). These responses suggest that the hypertensive response due to direct laryngoscopy and tracheal intubation is associated with redistribution of blood flow in the body. PMID- 8198274 TI - Effect of intravenous lidocaine on intraabdominal pressure response to airway stimulation. AB - We evaluated the effect of intravenous (i.v.) lidocaine (1 or 2 mg/kg) on increases in intraabdominal pressure (IAP) due to carinal stimulation in anesthetized patients. IAP was measured continuously using a transurethral bladder catheter. Before administration of lidocaine, carinal stimulation by suction catheter increased IAP compared with baseline values (P < 0.05). After i.v. administration of 1 mg/kg of lidocaine, carinal stimulation produced no change in IAP for 5 min, but IAP increased more than baseline at 7 min (P < 0.05); 2 mg/kg of lidocaine suppressed increase in IAP due to carinal stimulation until 7 min. Changes in IAP at 7 min were 42.2 +/- 12.2 mmHg in the 1 mg/kg group and 10.8 +/- 2.6 mmHg in the 2 mg/kg (P < 0.05). We conclude that increase in IAP caused by carinal stimulation is attenuated by i.v. lidocaine, and this effect continues for 5 min from 1 mg/kg of lidocaine and at least for 7 min from 2 mg/kg after administration. PMID- 8198276 TI - Comparative direct effects of lidocaine and bupivacaine on regional myocardial function in dogs at noncardiovascular toxic levels. AB - Although it is well recognized that accidental intravascular injection of bupivacaine during regional anesthesia can cause severe circulatory collapse, the direct cardiac effects at concentrations below the cardiotoxic level have not been described, despite increased use of regional anesthesia and its combination with general anesthesia. Therefore, the author compared the direct effects of bupivacaine and lidocaine on regional myocardial function at such concentrations in in situ beating hearts in dogs. Regional myocardial function was assessed during selective intracoronary infusion of lidocaine (0, 2, 5, 10, and 20 micrograms/mL in plasma) or bupivacaine (0, 0.5, 1.25, 2.5, and 5.0 micrograms/mL in plasma), while the left anterior descending coronary artery was perfused at constant flow with blood from the femoral artery. Lidocaine had a myocardial depressant effect (systolic shortening) at plasma concentrations greater than 10 micrograms/mL, whereas bupivacaine began to depress regional myocardial function at concentrations greater than 2.5 micrograms/mL. There was also a widening of the QRS interval during bupivacaine infusion at those concentrations. Post systolic shortening was more frequent during bupivacaine infusion (47.0% +/- 7.7%) at the plasma concentration (5 micrograms/mL) than during lidocaine infusion (33.2% +/- 7.4%) at the corresponding concentration (20 micrograms/mL). It is concluded that, although lidocaine and bupivacaine have no direct myocardial effects at clinical levels (below 5 micrograms/mL and 1.25 microgram/mL lidocaine and bupivacaine, respectively), they depress myocardial function at plasma concentrations near the cardiotoxic level with a relative toxicity ratio (1:4). This effect is more pronounced with bupivacaine at higher concentrations (> 5 micrograms/mL) than with lidocaine at corresponding concentrations (> 20 micrograms/mL). PMID- 8198275 TI - Specific gravities of desflurane, enflurane, halothane, isoflurane, and sevoflurane. AB - We determined the specific gravities of presently available volatile anesthetics in order to supply a consistent quantitative basis for calibration standards. Using four 50-mL volumetric flasks, we obtained the following values at 20 degrees C: desflurane 1.4651 +/- 0.0004 g/mL (mean +/- SD); enflurane 1.5230 +/- 0.0003 g/mL; halothane 1.8680 +/- 0.0007 g/mL; isoflurane 1.5019 +/- 0.0006 g/mL; and sevoflurane 1.5203 +/- 0.0008 g/mL. Measurements made at 0 degree C, 10 degrees C, 20 degrees C, and 25 degrees C (not for desflurane at 25 degrees C) revealed a decrease in specific gravity of 0.00250 +/- 0.00014 g/mL for each degree of increase in temperature. These data bear on the issue of cost for anesthetics that are stored as liquids, but used as gases. PMID- 8198277 TI - Synergistic antinociceptive interactions among drugs administered to the spinal cord. PMID- 8198278 TI - Hepatic necrosis associated with herpesvirus after anesthesia with desflurane and nitrous oxide. PMID- 8198279 TI - Pulmonary edema after nadbath and retrobulbar blocks. PMID- 8198280 TI - The misplaced intraaortic balloon pump. PMID- 8198281 TI - Interluminal communication in a pulmonary artery catheter causing artifactual pressure measurement. PMID- 8198282 TI - Laparoscopic-assisted repair of a traumatic ruptured diaphragm. PMID- 8198283 TI - Epidural anesthesia for cesarean delivery and vaginal birth after maternal Fontan repair: report of two cases. PMID- 8198284 TI - The management of status epilepticus with a continuous propofol infusion. PMID- 8198285 TI - Ipsilateral stellate ganglion block effective for treating shoulder pain after thoracotomy. PMID- 8198286 TI - Russell-Silver syndrome: anesthetic implications. PMID- 8198287 TI - Propofol and the patient with hereditary coproporphyria. PMID- 8198288 TI - Pressure rate quotient revisited. PMID- 8198289 TI - Airway obstruction on cricoid pressure is not glottic. PMID- 8198290 TI - Water-saline controversy or deficient regional anesthesia training? PMID- 8198291 TI - Commercial drug supplements should include costs. PMID- 8198292 TI - Lighted stylet intubation: greasing your way to success. PMID- 8198293 TI - The laryngeal mask airway and laryngeal polyposis. PMID- 8198294 TI - Pulmonary edema after absorbing crystalloid irrigating fluid during laparoscopy. PMID- 8198295 TI - Outcome of cardiovascular collapse in pediatric blunt trauma. AB - STUDY OBJECTIVES: To determine the survival and functional outcome of pediatric blunt trauma victims demonstrating cardiovascular collapse, including pulseless cardiopulmonary arrest or severe hypotension, on initial presentation in an emergency department. DESIGN: Seven-year consecutive case-control series. SETTING: Level I trauma center and university teaching hospital. PARTICIPANTS: Two thousand one hundred twenty consecutive pediatric victims of blunt trauma less than 16 years old admitted to a Level I trauma center from August 1984 through December 1991 had a mortality of 5.2%. Thirty-eight patients (1.8%) demonstrated pulseless cardiac arrest or severe hypotension (systolic blood pressure of 50 mm Hg or less) on initial presentation in the ED. INTERVENTIONS: All patients received basic and advanced life support consistent with guidelines published by the American Heart Association, American Academy of Pediatrics, and American College of Surgeons. MEASUREMENTS AND MAIN RESULTS: Survival, functional outcome, and donor status were reviewed. Outcome of ED resuscitation (death or reanimation), post-ED destination (morgue, operating room, or pediatric ICU) length of hospitalization, functional outcome after hospital discharge, time to death (time from admission to ED to declaration of death), cause of death, total hospital costs, total hospital charges, and organ donation were reviewed. There were no functional survivors among 38 pediatric victims of blunt trauma who presented to the ED in pulseless cardiac arrest or with severe hypotension. Eleven of the 12 patients who were transferred to the pediatric ICU died; the single survivor demonstrated profound neurologic impairment six years after hospitalization. Six of these 12 patients were eligible potential donors and resulted in four multiorgan donors during the seven-year study. The mean hospital unreimbursed care for the 38 study patients was $3,514 per patient. CONCLUSION: No child who presented with pulseless cardiac arrest or severe hypotension following blunt trauma achieved functional survival. Reimbursed care for pediatric victims of blunt trauma demonstrating cardiovascular collapse is disproportionately poor compared with that for pediatric patients who maintain hemodynamic integrity in the ED. Half of all patients who were stabilized sufficiently for transfer to the pediatric ICU were eligible potential organ donors. Therefore aggressive resuscitation of these patients may be justified if organ donation is seriously contemplated and aggressively pursued. PMID- 8198296 TI - Evaluation of SaO2 as a predictor of outcome in 280 children presenting with acute asthma. AB - STUDY OBJECTIVES: To evaluate the initial measurement of arterial oxygen saturation (SaO2) as a predictor of outcome in acute childhood asthma compared with other factors of past and present asthma history. DESIGN: Prospective observational double-blind study. SETTING: The emergency department of an urban pediatric hospital with a 1988 annual census of 50,000 children. TYPE OF PARTICIPANTS: Two hundred eighty children with recurrent wheezing that was diagnosed by a physician as asthma, who presented to the ED with wheezing. INTERVENTION: SaO2 was measured on arrival in the ED, and a detailed history of the present attack and past asthma was recorded. Children were treated according to then-current practice guidelines. Parents were contacted by telephone to determine the outcome of the attack; a "poor outcome" was defined as admission to hospital or re-presenting with ongoing symptoms to receive medical care if sent home from the ED. A "worst outcome" was defined as receiving IV aminophylline and steroids after failing to respond to repeated bronchodilation and oral steroids. MEASUREMENTS AND MAIN RESULTS: The proportion of children at each percent SaO2 who had a poor outcome increased with decreasing SaO2 (r = .97). Likelihood ratios for a poor outcome were 35 (confidence interval [CI], 11 to 150) for an SaO2 of 91% or less compared with 96% or more and 4.2 (CI, 2.2 to 8.8) for an SaO2 of 92% to 95% compared with 96% or more. An SaO2 of 91% or less predicted with a sensitivity of 100% and a specificity of 84% those children with a worst outcome who required IV therapy. Other factors of current or past asthma history failed to predict outcome. CONCLUSION: We have shown that in acute childhood asthma, the initial level of SaO2 reflects severity as it predicts the likelihood of poor outcome. This predictive quality of SaO2 is independent of current or past clinical factors. PMID- 8198298 TI - Violence in the pediatric emergency department. AB - STUDY OBJECTIVE: To identify the frequency of violence and the perception of safety in pediatric emergency departments. STUDY DESIGN: Descriptive, cross sectional survey of directors of pediatric EDs with fellowship programs. SETTING: University-based urban pediatric EDs. PARTICIPANTS: Forty-seven pediatric ED directors were surveyed, with 94% responding. RESULTS: More than three-fourths of those responding reported one or more verbal threats per week; 77% reported one or more physical attacks on staff per year; and 25% reported actual injury to staff. No pediatric EDs had weapon detectors; 7% had city police stationed there; and 54% had 24-hour security stationed in the pediatric ED. The majority reported that their staff members practice with at least occasional fear (55%) and had documented this concern (82%). Perception of safety was associated with the incidence of verbal threats (P < .006), physical attacks (P < .03), injury to staff or patient (P < .01), and the frequency with which security was needed (P < .001). Pediatric EDs with 50,000 or more visits per year were more likely to have multiple physical attacks on staff (relative risk, 2.89; 95% confidence interval, 1.33-6.26; P < .004). More verbal threats were reported in pediatric EDs with longer waiting times (P < .001). Fewer than half of the pediatric EDs with reported injuries had 24-hour security. CONCLUSION: Pediatric EDs are not immune to the problem of violence. Efforts must be directed to increase safety through better security, more efficient patient care, and aggression management training. PMID- 8198297 TI - Emergency intubation of the pediatric medical patient: use of anesthetic agents in the emergency department. AB - STUDY OBJECTIVES: To delineate the diagnoses of children who required emergency intubation, to ascertain which medications were used, and to describe the complications of intubation and their association with the choice of medications. DESIGN, SETTING, AND TYPE OF PARTICIPANTS: Three-year retrospective study of 60 intubations of critically ill pediatric patients by pediatric emergency physicians in the emergency department setting. MEASUREMENTS AND MAIN RESULTS: Clinical complications were noted for intubations with neuromuscular paralysis and intubations initially attempted without a paralyzing agent. Intubations attempted without neuromuscular paralysis resulted in a higher rate of complications (53% versus 26%) and a greater risk of more than one complication per intubation. This finding appeared to be independent of physicians' clinical experience. CONCLUSION: Rapid-sequence protocols with paralysis facilitate intubations in the complex pediatric patient in the ED setting. PMID- 8198299 TI - Rectal bleeding in the pediatric emergency department. AB - STUDY OBJECTIVES: To describe the presumptive diagnoses in an unselected, ambulatory, pediatric population complaining of rectal bleeding; to determine how often those diagnoses changed with follow-up; and to determine how often the bleeding represented an acutely life-threatening condition. DESIGN: Retrospective case series. SETTING: Urban, tertiary care pediatric emergency department. PARTICIPANTS: One hundred four patients with 109 visits with a chief complaint of blood in the stool. INTERVENTIONS: None. MAIN RESULTS: Follow-up was available on 95 of 109 visits (87.1%), with a mean duration of 7.5 months. A specific presumptive etiology was established for 73 of 109 patients (67%) at the initial ED visit and for 74 of 95 patients (77%) at follow-up. The etiologies varied markedly by age. Four patients (4.2%; 95% confidence interval, 0.2% to 8.2%) presented with a life-threatening condition (requiring an RBC transfusion or operative intervention): intussusception (three patients) and Meckel's diverticulum (one patient). Concordance between the ED diagnosis and the follow up diagnosis was 81%. CONCLUSION: A complaint of rectal bleeding is typically not life threatening in children. Emergency physicians normally are able to establish a presumptive diagnosis, which usually remains the same with follow-up. PMID- 8198300 TI - Clinical prediction of emergency cranial computed tomography results. AB - STUDY PURPOSE: To determine the ability of clinicians to predict the results of emergency head computed tomography (CT) scans. METHODS: Clinicians requesting cranial CT scans from the emergency department prospectively filled out a form detailing their patients' complaints, possible diagnoses, and the likelihood of finding those diagnoses on CT. The results of the scans were catalogued according to diagnosis and classified as acutely abnormal, chronically abnormal, or normal. RESULTS: Analysis of 536 consecutive patients showed a significant direct correlation between clinical prediction of CT abnormality and scan results. No definite differences in the ability to predict scan results were observed among different physician training levels. Thirty-six patients had acute abnormalities on CT despite a clinical prediction of remote or low likelihood. CONCLUSION: Although clinical predictions of CT abnormality correlate with actual CT results, the correlation is not adequately refined to rely on for selection of patients for emergency cranial CT scans. PMID- 8198301 TI - The role of neuroimaging in the initial management of patients with minor head injury. AB - STUDY OBJECTIVE: To determine whether omitting neuroimaging in the primary assessment of patients with minor head injuries in the emergency department is safe. DESIGN: Prospective cohort study. SETTING: University hospital, Copenhagen County Hospital, Glostrup, Denmark. PARTICIPANTS: The study group consisted of 2,204 patients presenting to the ED after sustaining minor head injuries. Only patients able to talk and walk were included. MEASUREMENTS AND MAIN RESULTS: The decision to admit was based exclusively on clinical guidelines in which the findings in the ED were of highest priority. Seven patients (0.3%) had a skull radiograph; computed tomography was not used in the primary evaluation. Four hundred thirty patients (19.5%) were admitted. After hospitalization, four patients developed intracranial complications. One required surgery, two required hyperventilation, and one was observed. Follow-up demonstrated that no patient with an intracranial complication had been missed. CONCLUSION: We found it safe to exclude neuroimaging in the primary assessment of patients with minor head injuries in the ED, and to rely instead on clinical criteria. PMID- 8198302 TI - Validation of diphenhydramine as a dermal local anesthetic. AB - STUDY OBJECTIVE: Although diphenhydramine has been recommended as an alternate local anesthetic for patients claiming allergy to lidocaine, no prior placebo controlled evaluations of diphenhydramine for dermal anesthesia have been performed. We sought to determine the relative efficacy of diphenhydramine compared to saline placebo and lidocaine. DESIGN: Prospective, randomized, double blind, placebo-controlled clinical trial. SETTING AND PARTICIPANTS: Twenty-four healthy adult volunteers. INTERVENTIONS: Subjects received intradermal 0.5-mL injections of diphenhydramine 1%, diphenhydramine 2%, lidocaine 1%, and normal saline placebo in a randomized, double-blind fashion. Extent of anesthesia (in mm2) was assessed at one, two, five, ten, 20, and 30 minutes. Pain of initial infiltration was assessed with a visual analog scale. MEASUREMENTS AND MAIN RESULTS: Diphenhydramine 1% produced greater anesthesia than placebo (P < .001) and equivalent anesthesia to lidocaine 1% (P = .889). (Our sample size had 90% power to detect a difference of 30% from the peak anesthesia observed.) Diphenhydramine 2% was less effective than diphenhydramine 1%; however, this difference was not statistically significant (P = .295). Infiltration of either concentration of diphenhydramine was significantly more painful than either lidocaine or saline (P < or = .001) for all comparisons). No clinically important complications were noted. CONCLUSION: In this study of 24 adult volunteers, diphenhydramine 1% was as effective as lidocaine 1% for achieving dermal local anesthesia, although injection was more painful. Although no clinically important complications were noted in our study, the safety of diphenhydramine remains to be established, especially in areas with poor collateral perfusion (eg, digits, pinna, and nose). PMID- 8198303 TI - The effectiveness of strapping techniques in spinal immobilization. AB - STUDY OBJECTIVES: To test the effectiveness of strapping techniques in reducing lateral motion of volunteers restrained on a backboard. DESIGN: Randomized block experimentation. SETTING: Medical products research and design laboratory. PARTICIPANTS: Healthy adult volunteers with no history of head, neck, or back trauma. INTERVENTIONS: Subjects were restrained on a wooden backboard using a control and three variations of strapping techniques. The backboard was rolled 90 degrees to the side, and lateral motion of the torso was measured. MEASUREMENTS AND MAIN RESULTS: Nineteen subjects participated. Technique 2, which added an abdominal strap to the control technique, reduced 26% of the lateral motion. CONCLUSION: Additional, specifically placed strapping should be added to the torso to reduce lateral motion on a backboard. Further study is needed to determine the effect of lateral motion in the spine and potential benefits of reduced motion. PMID- 8198304 TI - Comparison of digital versus metacarpal blocks for repair of finger injuries. AB - STUDY OBJECTIVE: This study compared efficacy, degree of discomfort, and time to anesthesia of digital blocks and metacarpal blocks for digital anesthesia. DESIGN: Randomized, prospective, nonblinded, clinical study conducted from April 1992 to January 1993. Patients served as their own controls. SETTING: Inner-city and community hospital emergency departments. TYPE OF PARTICIPANTS: Convenience sample of 30 adult patients, with third or fourth finger injuries including and distal to the proximal interphalangeal joint that required digital anesthesia. INTERVENTIONS: Digital blocks and a metacarpal blocks were performed (one per side) on all 30 patients (total of 60 blocks). The order of the blocks was randomized. MEASUREMENTS: A digital block and a metacarpal block were performed on each patient. Patients immediately rated the pain associated with each technique on a nonsegmented visual analog scale. Efficacy was assessed by requirement for additional anesthesia and anesthesia to pinprick. Time to anesthesia was assessed after each block in 23 patients. RESULTS: Mean visual analog scale pain scores were 2.53 for digital block and 3.38 for metacarpal block (P = .1751, Student's t-test). Metacarpal block failed anesthesia to pinprick in 23% of patients compared to 3% for digital block (P = .0227, chi 2). Time to anesthesia was significantly shorter for digital block compared to metacarpal block, with a mean of 2.82 minutes versus 6.35 minutes (P < .0001, Student's t-test). CONCLUSION: Digital block and metacarpal block, as described in this study, are equally painful procedures. Digital block, however, is more efficacious and requires significantly less time to anesthesia for the injured finger. PMID- 8198305 TI - Exercise-induced rhabdomyolysis. AB - STUDY OBJECTIVE: To describe the syndrome of exercise-induced rhabdomyolysis and to investigate the relation between exercise-induced rhabdomyolysis and the development of acute renal failure. DESIGN: Retrospective chart analysis on all patients with a discharge diagnosis of rhabdomyolysis from January 1988 to January 1993. SETTING: An urban tertiary care center with 225,000 annual emergency department visits. TYPE OF PARTICIPANTS: Thirty-five patients met the inclusion criteria for exercise-induced rhabdomyolysis: a history of strenuous exercise, creatine phosphokinase level more than 500, and urine dipstick positive for blood without hematuria. We excluded patients with a history of trauma, myocardial infarction, stroke, or documented sepsis. Charts also were examined for the presence of nephrotoxic cofactors (ie, hypovolemia and/or acidosis). RESULTS: All 35 patients were men without significant past medical history and were an average age of 24.4 years. The average admission creatine phosphokinase was 40,471 U/L. No patient presented with or developed nephrotoxic cofactors during hospitalization. None of our study patients experienced acute renal failure. CONCLUSION: Previous literature has described a 17% to 40% incidence of acute renal failure in rhabdomyolysis. None of our patients developed acute renal failure, signifying a much lower incidence of acute renal failure in exercise induced rhabdomyolysis without nephrotoxic cofactors than in other forms of rhabdomyolysis. PMID- 8198306 TI - Hand washing frequency in an emergency department. AB - STUDY OBJECTIVE: Previous studies, conducted mainly in ICUs, have shown low compliance with hand-washing recommendations, with failure rates approaching 60%. Hand washing in the emergency department has not been studied. We examined the frequency and duration of hand washing in one ED and the effects of three variables: level of training, type of patient contact (clean, dirty, or gloved), and years of staff clinical experience. DESIGN: Observational. SETTING: ED of an 1,100-bed tertiary referral, central city, private teaching hospital. PARTICIPANTS: Emergency nurses, faculty, and resident physicians. Participants were informed that their activities were being monitored but were unaware of the exact nature of the study. INTERVENTIONS: An observer recorded the number of patient contacts and activities for each participant during three-hour observation periods. Activities were categorized as either clean or dirty according to a scale devised by Fulkerson. The use of gloves was noted and hand washing technique and duration were recorded. A hand-washing break in technique was defined as failure to wash hands after a patient contact and before proceeding to another patient or activity. RESULTS: Eleven faculty, 11 resident physicians, and 13 emergency nurses were observed. Of 409 total contacts, 272 were clean, 46 were dirty, and 91 were gloved. Hand washing occurred after 32.3% of total contacts (SD, 2.31%). Nurses washed after 58.2% of 146 contacts (SD, 4.1%), residents after 18.6% of 129 contacts (SD, 3.4%), and faculty after 17.2% of 134 contacts (SD, 3.3%). Nurses had a significantly higher hand washing frequency than either faculty (P < .0001) or resident physicians (P < .0001). Hand washes occurred after 28.4% of 272 clean contacts (SD, 2.34%), which was significantly less (P < .0001) than 50.0% of 46 dirty contacts (SD, 7.4%) and 64.8% of 91 gloved contacts (SD, 5.0%). The number of years of clinical experience was not significantly related to hand-washing frequency (P = .82). Soap and water were used in 126 of the hand washes, and an alcohol preparation was used in the remaining six. The average duration of soap-and-water hand washes was 9.5 seconds. CONCLUSION: Compliance with hand washing recommendations was low in this ED. Nurses washed their hands significantly more often than either staff physicians or resident physicians, but the average hand-washing duration was less than recommended for all groups. Poor compliance in the ED may be due to the large number of patient contacts, simultaneous management of multiple patients, high illness acuity, and severe time constraints. Strategies for improving compliance with this fundamental method of infection control need to be explored because simple educational interventions have been unsuccessful in other health care settings. PMID- 8198307 TI - Defining the positive tilt test: a study of healthy adults with moderate acute blood loss. AB - STUDY OBJECTIVES: To define a set of orthostatic vital signs that minimize the frequency of false-positives among healthy individuals while maximizing sensitivity in detecting acute moderate blood loss and to determine the sensitivity and specificity of this optimized tilt test in detecting acute moderate blood loss. DESIGN AND INTERVENTION: Postural vital signs were recorded in a standardized manner before and after 450-mL phlebotomy. Paired comparisons were done for a variety of criteria for a positive tilt test using receiver operating characteristic curves. SETTING AND TYPE OF PARTICIPANTS: Three hundred forty-five healthy euvolemic adult volunteer blood donors were tested at three community blood donation centers over a one-year period. Subjects were prospectively divided into group 1 (less than age 65; 301) and group 2 (age 65 or older; 44). MEASUREMENTS AND MAIN RESULTS: For each combination of pulse and blood pressure in group 1, a change in pulse alone had the same or higher sensitivity with at least the same specificity. Pulse alone was similarly superior in group 2 compared with previously published combinations of pulse and blood pressure. Even the optimized tilt test had limited sensitivity in detecting acute moderate blood loss with high specificity. CONCLUSION: In applying the tilt test to young adults without cardiovascular disease, pulse measurement usually is all that is necessary. PMID- 8198308 TI - Efficacy of pseudoephedrine for the prevention of barotrauma during air travel. AB - STUDY OBJECTIVE: To determine the efficacy of decongestant prophylaxis in the prevention of symptoms of middle ear barotrauma (aerotitis media) during air travel. DESIGN: Prospective, parallel, double-blind, randomized trial. SETTING: Two commercial airports in Michigan. TYPE OF PARTICIPANTS: Two hundred fifty volunteers with a history of recurrent ear discomfort during air travel. INTERVENTIONS: Following randomization, each subject received 120 mg pseudoephedrine or placebo 30 minutes before flight departure. Recorded data included subject demographics, history of ear discomfort, and otologic examination. After arrival at their final destinations, volunteers were asked to complete a questionnaire and return it by mail to the investigators. Questions included the intensity and duration of otologic symptoms experienced while flying and possible drug side effects. MEASUREMENTS AND MAIN RESULTS: One hundred ninety subjects completed the study; 96 received 120 mg of pseudoephedrine and 94 received a placebo. The two treatment groups were similar with regard to age, sex, weight, and flight profile (P > .1). Ear discomfort was present in 32% (31 of 96) of those receiving pseudoephedrine versus 62% (58 of 94) of the control group (chi 2 = 15.34; P = .0001). Adverse effects were minimal; seven patients experienced drowsiness. CONCLUSION: Our results suggest that use of an oral decongestant before flying decreases the incidence of middle ear barotrauma associated with ambient pressure changes during air travel. PMID- 8198309 TI - 1% lidocaine versus 0.5% diphenhydramine for local anesthesia in minor laceration repair. AB - STUDY OBJECTIVE: Our previous study demonstrated that 1% diphenhydramine is as effective as 1% lidocaine for anesthesia in minor laceration repair, but that it also is more painful to inject. The purpose of this study was to compare 0.5% diphenhydramine to 1% lidocaine for pain of injection and adequacy of local anesthesia. STUDY DESIGN: Randomized, double-blinded, prospective study from December 1991 through June 1992. SETTING: University-affiliated, urban, inner city emergency department. PARTICIPANTS: Ninety-eight adults with linear skin lacerations without end-organ involvement were included; 48 received lidocaine and 50 received diphenhydramine. INTERVENTIONS: Wounds were anesthetized with either diphenhydramine or lidocaine according to a random table. Both patients and physicians rated the pain of injection and suturing according to a standard, previously tested, visual analog scale. MEASUREMENTS AND MAIN RESULTS: Patient and physician ratings were ranked without regard to treatment group, and rank sum scores were calculated for each group. General linear models and multivariate analysis of variance were used to analyze the ranked sum scores. The power of the study to detect a ranked sum difference of 15 was 0.8 with P < .05 considered statistically significant. Lidocaine was found to be significantly more effective as a local anesthetic for facial lacerations according to both patients (P < .002) and physicians (P < .004). There was no statistically significant difference between 1% lidocaine and 0.5% diphenhydramine for pain of injection or suturing for all other locations according to both patients and physicians. Overall mean and median scores for injection and suturing with diphenhydramine corresponded to the mild pain category according to patients. CONCLUSION: Although not a replacement for lidocaine, diphenhydramine is a viable alternative for anesthesia in the repair of minor lacerations. PMID- 8198310 TI - Emergency department two-dimensional echocardiography in the diagnosis of nontraumatic cardiac rupture. AB - Myocardial rupture is a catastrophic complication of acute myocardial infarction that usually results in sudden death. If diagnosed quickly, patients with myocardial rupture may be salvaged. This report describes the application of emergency department two-dimensional echocardiography in the diagnosis of six cases of myocardial rupture over two years. Each demonstrated a characteristic hemopericardium on limited single-window examination. These included four patients who met institutional guidelines for thrombolytic therapy. Three patients survived surgical repair, with two long-term survivors. PMID- 8198311 TI - Point: ethical emergency medicine group practice--an oxymoron? PMID- 8198312 TI - Counterpoint: contract management groups--a detriment to the specialty and practitioners of emergency medicine. PMID- 8198313 TI - Emergency ultrasound: echoes of the future. PMID- 8198314 TI - The HIV-positive physician and disability insurance. AB - Occupational exposure to HIV is becoming a daily hazard in many emergency departments. Emergency physicians who are protected by disability insurance policies are likely to believe that if they are unable to continue working because of HIV-positive status, their disability policies will provide them with a source of income. Unfortunately, analysis of case law regarding claims under disability policies shows that the law is unlikely to consider an asymptomatic, HIV-positive physician disabled for purposes of payments under disability policies. Therefore, it is necessary for emergency physicians to make sure this issue is resolved before buying and relying on a disability policy so that an anticipated safety net will be operative over the full range of hazards that emergency physicians face. PMID- 8198315 TI - Spontaneous cervical epidural hematoma. AB - Spontaneous cervical epidural hematoma is a rare cause of neck pain. We present the case of a 64-year-old woman who presented to the emergency department with neck pain from a partial Brown-Sequard syndrome secondary to spontaneous cervical epidural hematoma. The prompt recognition of this entity resulted in a favorable outcome. PMID- 8198316 TI - Sertraline intoxication in a child. AB - We describe severe sertraline intoxication in a child after accidental ingestion. Sertraline is a new antidepressant that has potent and selective inhibition of neuronal serotonin reuptake. Drug company-sponsored research has suggested little toxicity for this compound. Our patient exhibited prolonged tachycardia, hypertension, hallucinations, coma, hyperthermia, tremors of all extremities, and skin flushing. Clinicians should consider the possibility of serotonin syndrome among patients with similar clinical features and a recent history of sertraline or other serotonergic agent ingestion. PMID- 8198317 TI - Choreoathetotic movement disorder in a boy with Mycoplasma pneumoniae encephalitis. AB - We present a case of a 10-year-old boy who presented to the emergency department with high fever, acute choreoathetosis, weakness, and dysarthria. An EEG showed generalized slowing, and serologies defined an acute case of Mycoplasma pneumoniae encephalitis. This report describes the most common presentations, therapy, and outcomes of M pneumoniae encephalitis. PMID- 8198318 TI - Definitive diagnosis and location of peanuts in the airways using magnetic resonance imaging techniques. AB - A 14-month-old boy suspected to have aspirated peanut fragments into the airways was transferred to our hospital. His chest radiographs revealed Holzknecht's sign, which indicated left mainstem bronchial obstruction. Magnetic resonance imaging with T1-weighted images clearly showed a high-intensity signal of peanut fragments in the left mainstem bronchus. Removal was performed by bronchoscopy in a shorter time under general anesthesia. Magnetic resonance imaging with T1 weighted images (T1WI) is useful for definitive diagnosis and location of peanut fragments in the lower airway because the peanut material appears as a high intensity signal surrounded by the low-intensity lung tissue. Various slice orientations of T1WI provide accurate information concerning anatomic location of such fragments, thus facilitating removal by bronchoscopy. PMID- 8198319 TI - The danger of scald burns during hair braiding. AB - The cases are presented of three patients who sustained scald burns after placing their braided hair in boiling water to set the braids. Caretakers and cosmetologists should be warned of the potential danger from scald burns when setting hair braids. Emergency physicians should be aware of this mechanism of injury for scald burns to the scalp, face, back, and neck regions. PMID- 8198320 TI - Successful resuscitation of a severely hypothermic neonate. AB - A profoundly hypothermic 5-hour-old infant in cardiac arrest was brought to the emergency department by paramedics. The infant was found wrapped in a garbage bag inside a freezer. She had been in the freezer for approximately four hours. Her initial rectal temperature was 16.2 degrees C. Active external and core warming modalities, including warm blanket, radiant heat lamp, warm humidified air, heated gastric lavage, and heated bladder lavage, were used to rewarm the infant. Her temperature rose to 30.5 degrees C in three hours (4.8 degrees C/hr). The infant converted from a slow idioventricular rhythm to sinus bradycardia at 49 minutes (20.4 degrees C) into the resuscitation. At 53 minutes (21.5 degrees C), the infant moved both upper extremities. At the time of discharge from the hospital, she had no significant physical or neurologic problems. Neurologic examination at 4 months was normal. This report supports prior recommendations to aggressively rewarm severely hypothermic infants in cardiac arrest. PMID- 8198321 TI - ED patients with atypical chest pain. PMID- 8198322 TI - Utility of the biofragmentable anastomotic ring in traumatic small bowel injury. AB - OBJECTIVE: To evaluate the use of the 25 mm Biofragmentable Anastomotic Ring (BAR) in traumatic small bowel injury. METHODS: In a one year prospective, nonrandomized study, 18 patients (x age = 25 yrs) with penetrating small bowel injury had 25 BAR devices placed to restore intestinal continuity. Using one-way analysis of variance, this group was compared to 63 historical controls (x age = 27 yrs) with small bowel trauma who had either sutured or stapled anastomoses (SSA), with regard to Penetrating Abdominal Trauma Index (PATI) score, time until return of bowel function, and postoperative morbidity. RESULTS: PATI scores for the two groups were not significantly different (P = 0.099). No deaths in the SSA group (n = 8) or in the BAR group (n = 1) were related to the anastomotic technique. There was no significant difference (P = 0.991) in the rate of post operative intestinal obstruction between BAR (n = 3) and SSA (n = 8) groups; none of the BAR patients required re-operation. The average length of time for return of bowel function was not significantly different (P = 0.197) between BAR (4.3 days) and SSA (5.8 days) groups. CONCLUSIONS: The 25 mm BAR may be used in the repair of traumatic small bowel injury, based upon comparable outcomes when compared with sutured and stapled anastomoses. PMID- 8198323 TI - Intravenous pyelography in penetrating trauma. AB - Intravenous pyelograms (IVPs) are routinely used in the workup of suspected urologic injuries. The indications for obtaining IVPs have not been well characterized. This study examined 67 patients with penetrating trauma who received formal IVPs with nephrotomography in the radiology department. Of 35 stab wounds, 19 patients presented without hematuria and accounted for only one positive IVP. No intervention was undertaken in this patient. There were 14 stab wound patients with microscopic hematuria, with three positive IVPs. No intervention was necessary in any of these patients. The two remaining stab wound patients both had gross hematuria and renal injuries requiring intervention. However, only one of the two had a positive IVP, showing a blurred kidney margin. One patient had a pseudoaneurysm of a branch of the renal artery, and the other had an arteriovenous fistula. Of 32 patients with gunshot wounds, 15 presented without hematuria. Of the 15, one had a positive IVP but did not have a renal injury on exploration. None of the other 13 patients in this group undergoing exploration had renal injuries. Of the 11 patients with microscopic hematuria, three had hematomas and one had gross extravasation on IVP. Of the six patients with gross hematuria, three had positive IVPs, showing a hematoma, a renal fracture, and indistinct renal outline, respectively. In this limited study, omitting IVPs on the patients with negative urinalyses would not have missed any significant injuries. We suggest that more study is needed in this area because our present standard may lead to unnecessary expense and delay. PMID- 8198325 TI - Automated severity scoring in level I trauma patients. AB - The authors evaluated the sensitivity and specificity of a computerized Simplified Acute Physiology Score (SAPS) for outcome prediction in Level I trauma patients admitted to a Surgical ICU (SICU). SAPS was compared with the combined Trauma Score (TS) and Injury Severity Score (ISS). 1434 consecutive trauma patients admitted to the SICU over a 3-year period were studied. All patients had the SAPS automatically calculated on the first SICU day. Patient data was extracted from an electronic flowsheet, and the most abnormal values for the previous 24 hours were used to calculate the SAPS. TS and ISS were calculated by a trained nurse. The relationship among the severity scores, ICU length of stay (LOS), and survival was evaluated. A logistic regression equation was calculated for SAPS alone and for TS combined with ISS. The predictive power of the severity methods was compared using Receiver Operating Characteristic (ROC) curve analysis. Scores for survivors and non-survivors were compared with Student's t tests. 1085 patients had complete data available. There were 995 survivors and 90 non-survivors. The mean (+/- standard error of the mean) ISS was 12.7 (+/- 3.2) with 36 per cent of the patients having an ISS > or = 15. The mean SAPS was 8.1 (+/- 2.5). Survivors had a significantly lower SAPS than non-survivors, 7.0 versus 20.2 (P < 0.0005) and a shorter LOS, 2.5 versus 4.9 days (P < 0.002). ROC curve analysis revealed no statistically significant difference in the areas under the two curves, indicating that the SAPS was equivalent to TS combined with ISS in outcome prediction (P > 0.70).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198324 TI - Relationship of hyperglycemia and severity of illness to neurologic outcome in head injury patients. AB - Hyperglycemia upon hospital admission has been associated with poorer neurologic outcomes in patients with brain injury, but this relationship has not been well defined. To evaluate the relationship of hyperglycemia and severity of illness to neurologic outcome, the authors examined Surgical Intensive Care Unit (SICU) records for a 6 month period at a Level I trauma center. Of 276 trauma admissions, 97 patients had intracranial injuries. The peak glucose determination on the first day of admission was correlated with the Glasgow Coma Scale (GCS) score upon admission and discharge from the SICU and with severity of illness as measured by the Simplified Acute Physiology Score (SAPS). The mean admission GCS was 10.6 (+/- 0.49 S.E.M.), the mean glucose on the first SICU day was 146 (+/- 7.7 S.E.M.), and the mean peak glucose was 176 (+/- 8.2 S.E.M.). The peak glucose was inversely related to both GCS on admission and GCS at discharge (P < 0.001). However, stepwise multiple regression analysis revealed that the best single predictor of GCS at discharge was the GCS on admission. The next best predictor was the SAPS on the first SICU day. Peak glucose did not add to the power of admission GCS and SAPS to predict neurologic outcome. Peak glucose levels in brain-injured patients may simply reflect severity of illness and injury that is better represented by SAPS. PMID- 8198326 TI - The impact of the volume of neurotrauma experience on mortality after head injury. AB - The volume of neurotrauma experience and mortality after head injury were evaluated in 4667 patients admitted to 10 Level I trauma centers. The hospitals were divided into three groups based on the number of severely head-injured patients admitted each month. The mean number of patients admitted each month to Hospital Groups 1, 2, and 3 with a Glasgow Coma Scale (GCS) score > 10 was 100.0, 18.2, and 10.6. Mortality was significantly lower for patients admitted to Group 1 than for those admitted to Group 2 or 3; however, the difference between Groups 2 and 3 was not significant. The mean number of admissions with a GCS score < or = 10 was 8.3, 6.5, and 2.8, and mortality rates were 26.7 per cent, 36.5 per cent, and 41.4 per cent, respectively. Mortality for Group 1 patients was significantly lower than for those in Groups 2 or 3. Patient age also had a profound impact on survival among all hospital groups. We conclude that the volume of neurotrauma experience correlates with mortality after head injury. PMID- 8198327 TI - Gunshot wounds: 10-year experience of a rural, referral trauma center. AB - The 10-year experience of a Level II trauma center with 122 gunshot wounds referred from a large rural area was analyzed to illustrate differences from the experience of urban centers. Most frequent causes of injury were attempted suicide in 38 (31%) patients, hunting mishaps in 32 (26%), unintentional accidents in 29 (24%), and intentional assault in 18 (15%). Of weapons specified, rifles were documented in 48 (39%) instances, shotguns in 25 (21%), and handguns in 24 (20%). Body regions injured were the trunk in 47 (39%) patients, head in 35 (29%), lower extremity in 31 (25%), and upper extremity in 29 (24%). Twenty-five patients (20%) died as a result of their injuries. The cause of death was brain injury in 18 (72%), exsanguination from truncal wounds in 5 (20%), myocardial infarction in 1 (4%), and multiple organ failure in 1 (4%). We conclude that the distributions of cause and type of gunshot wounds are unique in a rural setting. These differences have profound consequences in designing effective prevention programs for our area and support the design of more efficient trauma systems for rural North America. PMID- 8198328 TI - Deep venous thrombosis in the trauma patient. AB - The incidence of deep venous thrombosis (DVT) in the trauma population and those risk factors which affect its development remain an enigma. We prospectively studied 100 trauma patients admitted to a Level I trauma center with duplex scans throughout their hospitalization. Fifteen patients (15%) developed DVT. The remaining 85 patients (85%) had no evidence of DVT during their hospitalization. The two groups were similar in sex ratio, Glasgow coma scale, trauma score, and type of injury. Fourteen patients (93%) with DVT had been given prophylactic treatment with 5,000 units of Heparin subcutaneously q12h, and 36 patients (42%) without DVT were similarly treated. The data in this study describe the incidence of DVT (15%) in the trauma population and those patients at most risk for its development. Patients admitted with high Injury Severity Scores and extremity injuries are at most risk for development of DVT. PMID- 8198329 TI - Fasciotomy in vascular trauma: is it too much, too often? AB - Fasciotomy has been used as a prophylactic measure against development of compartment syndrome and as a treatment modality when the syndrome has developed in patients suffering vascular trauma. The hospital records of 36 patients who underwent surgical repair of their traumatic vascular injuries were reviewed. All 36 patients had at least one indication for fasciotomy at the time of repair; i.e., ischemic time of more than 6 hours or combined arterial and venous injury. Prophylactic fasciotomies were performed in 18 of the patients at the time of vascular repair; 18 did not have fasciotomies performed at the time of initial repair. The decision to perform a fasciotomy was made by the operating surgeon based on well-defined criteria. Hospital stay was significantly longer for the fasciotomy group. Four of the fasciotomy-related complications were infective in nature. Only one patient who did not undergo fasciotomy at the time of original repair developed a compartment syndrome during the postoperative period. Selective fasciotomy based on well-defined criteria instead of serial physical examinations or measurement of compartment pressures will effectively save limbs; there is an increased hospital stay. PMID- 8198331 TI - Potential of laparoscopy to reduce non-therapeutic trauma laparotomies. AB - Standard diagnostic methods used to evaluate patients sustaining abdominal trauma result in non-therapeutic laparotomy rates ranging from 5 to 40 per cent depending upon the clinical situation. The purpose of this study was to assess the safety and efficacy of diagnostic laparoscopy in the identification of intra abdominal injuries in stable trauma patients. Twenty-one hemodynamically stable adult patients underwent laparoscopy prior to laparotomy for blunt (n = 10) or penetrating (n = 11) trauma, and the findings from each procedure were directly compared. Laparoscopy was 100 per cent accurate in detecting the need for laparotomy, although a number of specific injuries were not identified. There were no complications related to the procedure. Emergency laparoscopy is safe and should be considered in hemodynamically stable trauma patients with indications for laparotomy based on standard diagnostic criteria in order to minimize the incidence of non-therapeutic laparotomy. PMID- 8198330 TI - Two-dimensional echocardiogram in hemodynamically stable victims of penetrating precordial trauma. AB - Hemodynamically stable patients with penetrating precordial trauma present a diagnostic dilemma. Previous reports utilizing subxiphoid pericardial windows as the diagnostic measure demonstrated negative rates ranging from 75-82%. In an effort to decrease the high rate of negative invasive procedures, the following study was undertaken. PROTOCOL: All hemodynamically stable victims with penetrating precordial trauma were evaluated using emergent echocardiogram over a one year period at Grady Memorial Hospital. If the echocardiogram was negative for the presence of pericardial fluid, the patient was observed for 24 hours. If pericardial fluid was detected, the patient underwent a subxiphoid pericardial window. Patients requiring immediate surgery for other reasons, i.e. peritonitis, underwent a pericardial window during the procedure without preoperative echocardiogram. RESULTS: Fifty-three patients were entered into the study. The injuries sustained included 40 stab wounds, 11 gunshot wounds and 2 shotgun injuries. Two echocardiograms (8%) demonstrated > 20cc of fluid and were followed by pericardial windows. The remaining 51 patients did well without the need for pericardial window. Nine additional hemodynamically stable patients underwent pericardial windows without preoperative echocardiograms. Only one of these was positive with a cardiac injury proven at sternotomy. CONCLUSION: Echocardiogram is a sensitive noninvasive method of evaluating hemodynamically stable victims of penetrating chest wounds in proximity to the heart. PMID- 8198332 TI - Role of computed tomography scan in evaluating the widened mediastinum. AB - Thirty-eight blunt trauma patients with a suspicion of thoracic aortic injury were assessed by computed tomography (CT) scan, aortography, and chest x-ray. Twenty-eight of the 38 patients had widened mediastinum by chest x-ray; four of 13 CT scans were abnormal. No patient with a negative CT scan had aortic injury by aortogram. A normal, non-dynamic CT scan of the chest should influence one's decision-making in the need for aortography. PMID- 8198333 TI - Rectus sheath hematomas in hematological disorders. AB - Rectus Sheath Hematomas are an uncommon cause of abdominal pain. There are many etiologies for this entity. The physician must be aware of this entity and include it in his differential when a patient presents with acute abdominal pain. PMID- 8198334 TI - Increased incidence of thyroid cancer in patients with primary hyperparathyroidism: a continuing dilemma. AB - A number of previous studies have reported a greater incidence of thyroid disease in patients with primary hyperparathyroidism (HPT) than in normal patients. However, few of these studies utilized controls, and most have dealt only with gross thyroid nodules and not with total histologic abnormalities. In order to clarify this problem, thyroid pathology was determined in each of 100 consecutive patients operated upon for HPT. Thyroid nodules were excised, but in addition, a random biopsy of the thyroid was performed in all cases. Patients in this group were matched by age, race, and sex with non-HPT autopsy controls. Histologic slides were reviewed by a single pathologist blinded to the patient's group. Data for the matched pairs were analyzed by the Sign test. There was no significant difference in the prevalence of colloid nodular disease between patients with HPT (45) and the autopsy control group (43, P = 0.2). There was also no significant difference in the prevalence of lymphocytic thyroiditis between HPT patients (24) and control (15, P = 0.07). There was likewise no significant difference in the prevalence of other benign thyroid gland diseases between the two groups. Only nonmedullary cancer of the thyroid was shown to be statistically more prevalent in HPT patients than in autopsy controls (7% vs 0%, respectively; P < 0.02). The major factor that accounts for the coexistence of benign thyroid lesions and HPT is that both are prevalent in middle-aged women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198335 TI - The rationale for surgical treatment of mesenteric and retroperitoneal cysts. AB - Mesenteric and retroperitoneal cysts are rare, usually asymptomatic lesions. Because of this, several recommendations in the literature caution against operative therapy in the absence of symptoms. During a recent 10 year period, six patients presented to our hospital with symptomatic mesenteric or retroperitoneal cysts; two of these patients were septic and had infection within the cyst. All six patients underwent excision with complete resolution of symptoms and no morbidity. With the advent of frequent abdominal CT scanning for a variety of reasons, it is likely that more of these lesions will be noted in the future. In view of the potential for development of symptoms and complications, we feel that any good risk patient found to harbor such a cyst should undergo complete excision. PMID- 8198336 TI - The influence of diabetes mellitus on the risk of abdominal aortic surgery. AB - Risk factors and postoperative complications of 153 diabetics (DM) who underwent an abdominal aortic operation for occlusive disease or an intact aneurysm from 1964 through June, 1988 were compared with 970 nondiabetics (nonDM) who underwent similar operations during the same time period. Heart disease, hypertension, cerebrovascular disease, and renal insufficiency were more prevalent in diabetics. Postoperatively, DM had a statistically significant increase in the incidence of myocardial infarction (DM 5.2%, nonDM 2.1%, P = .0434) and wound infection (DM 2.6%, nonDM 0.6%, P = .0359). The incidence of renal failure (DM 1.3%, nonDM 1.0%), stroke (DM 2.0%, nonDM 0.6%), and death (DM 3.9%, nonDM 2.9%) was higher in diabetics, but the differences were not statistically significant (P = NS). Operative mortality was greater for patients operated on for aneurysm (DM 5.3%, nonDM 3.2%) than for patients operated for occlusive disease (DM 3.3% versus nonDM 2.7%). Diabetics treated with insulin or oral agents had a higher complication rate than diabetics treated with diet alone or nondiabetics (insulin 13.0%, oral 13.4%, diet 4.2%, nonDM 8.6%). This study finds that diabetic patients can undergo an abdominal aortic operation with operative mortality comparable to that of nondiabetics. Diabetics have more postoperative complications than nondiabetics, but only myocardial infarction and wound infection are of statistical significance. Diabetics treated with insulin or oral agents have more complications than do diabetics treated by diet alone or nondiabetics. PMID- 8198338 TI - Hamartomas of the breast. AB - Hamartomas of the breast are rare tumor-like lesions composed of ducts, lobules, fat, and fibrous tissue. The clinical and pathologic findings of six cases of patients ranging in age from 19 to 63 years are reported. Diagnosis is difficult, and we emphasize that fine needle aspiration and cytology of the smears is not diagnostic for hamartomas. PMID- 8198337 TI - Gallstone ileus: a review of 1001 reported cases. AB - Although rare in the general population, gallstone ileus accounts for 25 per cent of nonstrangulated small bowel obstructions in those over the age of 65. While mortality has declined over the years, it remains high at 15-18 per cent. This is largely due to the patient population, with comorbid medical conditions contributing to mortality. The proper extent of surgery continues to be actively debated. Proponents of minimal surgery feel that relief of the obstruction is all that is required. Others argue that the gallbladder and biliary-enteric fistula must be removed to prevent future recurrence (a one-stage procedure). The one stage procedure carries an associated mortality of 16.9 per cent, compared to 11.7 per cent for simple enterolithotomy. Morbidity after enterolithotomy is low. The recurrence rate of gallstone ileus was less than 5 per cent, and only 10 per cent of patients required reoperation for continued symptoms related to the biliary tract. Simple enterolithotomy is both safe and effective in dealing with a patient with gallstone ileus. PMID- 8198339 TI - Primary common bile duct closure following exploration: an effective alternative to routine biliary drainage. AB - Primary closure of the common bile duct following exploration has been safely and effectively performed, as advocated by Halsted, provided no evidence of pancreatitis, cholangitis, or ampullary obstruction exists. Using this precedent, the operative management and clinical course of 29 patients undergoing common bile duct exploration (CBDE) for choledocholithiasis from 1986 to 1992 were reviewed. Ten patients had primary closure of the common bile duct (CBD) following choledochotomy and exploration, and 17 patients had t-tube placement. Two patients had CBDE through an enlarged cystic duct that was then ligated. Patients were selected for t-tube placement if they had pancreatitis, ascending cholangitis, evidence of retained stones, or ampullary obstruction. Two patients in this series died. No patient with primary closure of the CBD suffered a biliary complication including retained stones, biliary fistula, pancreatitis, or bile peritonitis. Serious systemic complications were comparable in both groups. The results of this series support the safety of primary common bile duct closure in selected cases. PMID- 8198340 TI - Reversal of doxorubicin-impaired wound healing using triad compound. AB - Triad is composed of Na pyruvate, vitamin E, and unsaturated fatty acids. We found that Triad, administered orally or topically, reverses wound healing that is impaired by doxorubicin (Doxo) in rats. Rats given Doxo (6 mg/kg i.v.) were wounded with linear dermal incisions, and the wound-breaking strength (WBS) was compared among groups of rats differently treated with Triad. Five groups of five rats each were studied. Triad was given orally using a 20 per cent Triad/rat chow mixture and topically as a 50 per cent Triad/petroleum base salve administered daily. All groups were wounded at postoperative day 0, at which time Doxo was given to groups II-IV. Group IV was fed oral Triad 7 days prior to wounding and until POD 21. All wounds were harvested at POD 21, and the mean WBS of each group was obtained using an Instron Tensiometer. Doxorubicin impaired normal wound healing by 40 per cent. Oral Triad restored WBS in Doxo-treated rats to 88 per cent of control values; topical Triad restored WBS to 80 per cent of control values. Moreover, treatment with topical Triad and oral Triad increased the WBS by 30 per cent and 50 per cent when compared with Doxo-only-treated animals. In conclusion, Triad has been shown to restore wound healing to nearly normal levels in doxorubicin-impaired wounds. PMID- 8198341 TI - Treatment of septic shock with human monoclonal antibody HA-1A. A randomized, double-blind, placebo-controlled trial. CHESS Trial Study Group. AB - OBJECTIVE: To compare the effectiveness of 100 mg of HA-1A and placebo in reducing the 14-day all-cause mortality rate in patients with septic shock and gram-negative bacteremia in the Centocor: HA-1A Efficacy in Septic Shock (CHESS) trial, and to assess the safety of 100 mg of HA-1A given to patients with septic shock who did not have gram-negative bacteremia. DESIGN: Large, simple, group sequential, randomized, double-blind, multicenter, placebo-controlled trial. SETTING: 603 investigators at 513 community and university-affiliated hospitals in the United States. PATIENTS: Within 6 hours before enrollment, the patients had been in shock with a systolic blood pressure of less than 90 mm Hg after adequate fluid challenge or had received vasopressors to maintain blood pressure. These episodes of shock began within 24 hours of enrollment. A presumptive clinical diagnosis of gram-negative infection as the cause of the shock episode and a commitment from the patients' physicians to provide full supportive care were required. MEASUREMENTS: Blood cultures were obtained within 48 hours of enrollment, and death at day 14 after treatment was recorded. Adverse events occurring within 14 days after enrollment were also tabulated. RESULTS: 2199 patients were enrolled; 621 (28.2%) met all enrollment criteria, received HA-1A or placebo, and had confirmed gram-negative bacteremia. Mortality rates in this group were as follows: placebo, 32% (95 and HA-1A, 33% (109 of 328) (P = 0.864, Fisher exact test, two-tailed; 95% CI for the difference, -6.2% to 8.6%). Mortality rates in the patients without gram-negative bacteremia were as follows: placebo, 37% (292 of 793) and HA-1A, 41% (318 of 785) (P = 0.073, Fisher exact test, one-tailed; CI, -0.8% to 8.8%). CONCLUSIONS: In this trial, HA-1A was not effective in reducing the 14-day mortality rate in patients with gram-negative bacteremia and septic shock. These data do not support using septic shock as an indication for HA-1A treatment. If HA-1A is effective in reducing the mortality rate in patients dying from endotoxemia, these patients must be identified using other treatment criteria. PMID- 8198342 TI - Manuscript quality before and after peer review and editing at Annals of Internal Medicine. AB - OBJECTIVE: To evaluate the effects of peer review and editing on manuscript quality. SETTING: Editorial offices of Annals of Internal Medicine. DESIGN: Masked before-after study. MANUSCRIPTS: 111 consecutive original research manuscripts accepted for publication at Annals between March 1992 and March 1993. MEASUREMENTS: We used a manuscript quality assessment tool of 34 items to evaluate the quality of the research report, not the quality of the research itself. Each item was scored on a 1 to 5 scale. Forty-four expert assessors unaware of the design or aims of the study evaluated the manuscripts, with different persons evaluating the two versions of each manuscript (before and after the editorial process). RESULTS: 33 of the 34 items changed in the direction of improvement, with the largest improvements seen in the discussion of study limitations, generalizations, use of confidence intervals, and the tone of conclusions. Overall, the percentage of items scored three or more increased by an absolute 7.3% (95% CI, 3.3% to 11.3%) from a baseline of 75%. The average item score improved by 0.23 points (CI, 0.07 to 0.39) from a baseline mean of 3.5. Manuscripts rated in the bottom 50% showed two- to threefold larger improvements than those in the top 50%, after correction for regression to the mean. CONCLUSIONS: Peer review and editing improve the quality of medical research reporting, particularly in those areas that readers rely on most heavily to decide on the importance and generalizability of the findings. PMID- 8198343 TI - Urinary tract infection with an Enterococcus faecalis isolate that requires vancomycin for growth. AB - OBJECTIVE: To characterize the nutritional requirements and potential origin of a fastidious urinary tract Enterococcus faecalis isolate that apparently requires the antimicrobial agent vancomycin to grow. DESIGN: Case report and detailed microbiologic and molecular epidemiologic analysis. SETTING: University teaching hospital. MEASUREMENTS: Growth of the vancomycin-dependent strain was monitored using various standard laboratory media with and without supplementation with vancomycin and other substrates. This strain was compared with other vancomycin resistant but nondependent E. faecalis strains by examining plasmid profiles and pulsed-field gel electrophoresis patterns of genomic DNA and by analyzing vancomycin-resistance genes identified by the polymerase chain reaction. RESULTS: An E. faecalis isolate, strain TJ310, was isolated repeatedly from the urine of a patient receiving long-term vancomycin therapy. This strain grew in primary culture but not on subculture, suggesting an unusual growth requirement, and ultimately was found to require the glycopeptide antibiotic vancomycin to grow. Strain TJ310 appeared to be closely related to other vancomycin-resistant but nondependent E. faecalis isolates with the vanB genotype previously isolated from the same patient, suggesting that vancomycin dependence may have evolved in vivo in a vancomycin-resistant enterococcal strain during continuous exposure to high concentrations of vancomycin in the urine. CONCLUSIONS: This is the first reported example of a clinical bacterial isolate that requires an antimicrobial agent to grow. PMID- 8198344 TI - Neurohormonal and hemodynamic changes in severe cases of the ovarian hyperstimulation syndrome. AB - OBJECTIVE: To evaluate systemic hemodynamics, endogenous vasoactive neurohormonal factors (renin-angiotensin and sympathetic nervous systems, antidiuretic hormone, atrial natriuretic factor, and renal prostaglandins), and renal function in the severe ovarian hyperstimulation syndrome. DESIGN: Prospective longitudinal study. SETTING: Assisted-reproduction unit of a tertiary care hospital in Barcelona, Spain. PATIENTS: 31 consecutive patients having in vitro fertilization with development of ascites because of severe ovarian hyperstimulation syndrome. MEASUREMENTS: Mean arterial pressure; cardiac output; peripheral vascular resistance; hematocrit concentration; renal function; plasma renin activity; plasma aldosterone, norepinephrine, antidiuretic hormone, and atrial natriuretic peptide determinations; and urinary excretion of prostaglandin E2 and 6-keto prostaglandin-F1 were measured during the syndrome and 4 to 5 weeks after recovery (baseline). RESULTS: During the syndrome, patients showed increased hematocrits (mean of the paired difference, 0.047; 95% CI, 0.029 to 0.064), decreased mean arterial pressure (-16.6 mm Hg; CI, -19.8 to -13.6), increased cardiac output (2.6 L/min; CI, 2.13 to 3.17), and reduced peripheral vascular resistance (-709 dyne/s.cm-5;CI, -792 to -627). This was accompanied by marked increases of plasma renin (14.4 ng/L.s; CI, 9.87 to 18.90), norepinephrine (1.857 nmol/L; CI, 0.533 to 3.161), antidiuretic hormone (3.3 pg/mL; CI, 1.89 to 4.71), and atrial natriuretic peptide levels (9.7 fmol/mL; CI, 6.1 to 13.2). Hemoconcentration developed in 16 patients (mean of the paired difference in hematocrit concentration, 0.082; CI, 0.063 to 0.101) but not in 15 others (0.009; CI, 0.003 to 0.021). Both groups showed similar values for arterial pressure, cardiac output, and peripheral vascular resistance, but patients with hemoconcentration had higher (P < 0.05) levels of renin (mean, 20.97 ng/L.s[CI, 13.3 to 28.63] compared with 7.83 ng/L.s[CI, 4.08 to 11.58]), norepinephrine (3.907 nmol/L [CI, 3.057 to 4.757] compared with 2.417 [CI, 2.035 to 2.799]), and antidiuretic hormone (6.0 pg/mL [CI, 4.1 to 7.9] compared with 2.4 [CI, 1.7 to 3.03]). CONCLUSIONS: In addition to increased capillary permeability, severe ovarian hyperstimulation syndrome is consistently associated with arteriolar vasodilation. The simultaneous occurrence of these disorders leads to hyperdynamic circulatory dysfunction with marked stimulation of the sympathetic nervous system, renin-angiotensin system, and antidiuretic hormone. PMID- 8198345 TI - The hepatopulmonary syndrome masquerading as pulmonary Langerhans-cell histiocytosis. Hepatopulmonary Syndrome Study Group. PMID- 8198346 TI - Tuberculosis control strategies: the cost of particulate respirators. AB - OBJECTIVE: To assess the cost of the mandatory use of high-efficiency particulate respirators to treat patients with known or suspected tuberculosis. DESIGN: A questionnaire was used to determine the number of high-efficiency particulate respirators required and the number of cases of tuberculosis in employees that could potentially be prevented. Indirect costs included the training and fitness testing of employees. The clinical efficacy of respirators is not known. To provide a best-case scenario, it was assumed that the respirators could prevent as many as 25% of tuberculosis cases in health care workers. SETTING: 159 acute care facilities administered by the Department of Veterans Affairs. PARTICIPANTS: Quality improvement, infection control, and employee health specialists. MEASUREMENTS: Cost of the respirators compared with their maximum predicted efficacy. RESULTS: The use of the respirators would cost $7 million per case of tuberculosis prevented and $100 million per life saved. CONCLUSIONS: High efficiency particulate respirators are a costly means of trying to prevent tuberculosis. Costs could be reduced by reusing masks or by restricting the number of health care workers allowed to have contact with potentially infectious patients. As the health care budget undergoes further restrictions, specific means of accommodating the cost of new regulations must be found. PMID- 8198347 TI - Guidelines for medical treatment for stroke prevention. American College of Physicians. PMID- 8198348 TI - Blueberry muffins and mystery novels. PMID- 8198349 TI - Antiendotoxin antibodies: a dead end? PMID- 8198350 TI - Pulmonary function and gastroesophageal reflux in systemic sclerosis. AB - OBJECTIVE: To determine the relations among esophageal dysfunction, gastroesophageal reflux, and lung involvement in patients with systemic sclerosis. DESIGN: Retrospective review of esophageal motility, esophageal pH, and pulmonary function data. SETTING: University hospital outpatient clinic and community. PATIENTS: 39 consecutively referred patients who were grouped according to the presence or absence of abnormal distal (pH < 4.0 for > 5% of the 24-hour monitoring period) or proximal (pH < 4.0 for > 1% of the 24-hour period) gastroesophageal acid reflux. Patients were also grouped according to the presence or absence of distal esophageal peristalsis. MEASUREMENTS: Esophageal manometry, dual-probe (distal and proximal) esophageal 24-hour pH measurements, and pulmonary function studies (forced vital capacity, forced expiratory volume at 1 second, total lung capacity, and single-breath carbon monoxide diffusing capacity [DLco]). RESULTS: The mean total lung capacity (values as percentage predicted) was 87.1% +/- 11.2% (SD) for patients with abnormal proximal reflux and 77.8% +/- 21.6% for patients with normal proximal reflux (difference, 9.3%; 95% CI, -1.4% to 20.0%). The mean forced vital capacity for these patients was 91.1% +/- 12.4% and 85.4% +/- 25.6%, respectively (difference, 5.7%; CI, -6.9% to 18.1%). The mean total lung capacity was 83.8% +/- 15.4% for patients with abnormal distal reflux and 77.9% +/- 22.7% for patients with normal distal reflux (difference, 5.9%; CI, -7.6% to 19.4%). Among potential confounders of pulmonary measures, only smoking was related to decreased pulmonary function (smoking related to decreased DLco P < 0.01). Smoking was more common in patients with abnormal distal reflux than in those with normal distal reflux (65% compared with 25%, P = 0.03). After adjusting for smoking, the difference in mean DLco between patients with abnormal compared with normal distal reflux was 7.19% (Cl, -8.5% to 22.9%). CONCLUSION: Important measures of lung volume indicative of interstitial lung disease (total lung capacity, forced vital capacity) do not appear to be related to abnormal gastroesophageal acid reflux in patients with systemic sclerosis. PMID- 8198351 TI - Does editorial peer review work? PMID- 8198352 TI - Morbidity and mortality of renal dialysis: an NIH consensus conference statement. Consensus Development Conference Panel. PMID- 8198353 TI - The effects of aspirin on gastric prostaglandins. PMID- 8198354 TI - Omeprazole and vitamin B12. PMID- 8198355 TI - Nasal carriage of staphylococcal infection in Wegener granulomatosis. PMID- 8198356 TI - The Cushing syndrome induced by atrial natriuretic peptide-producing thymic carcinoid. PMID- 8198357 TI - Are protected environments necessary for recipients of bone marrow transplants? PMID- 8198358 TI - Not for students only. PMID- 8198359 TI - "Do everything". PMID- 8198360 TI - Preventing rheumatic heart disease in developing countries. PMID- 8198361 TI - Viscoelastic substance in the anterior chamber elevates intraocular pressure. AB - An 85-year-old man underwent an extracapsular cataract extraction OD with posterior chamber intraocular lens implantation. Sodium hyaluronate (0.3 mL) was used during the procedure, and approximately 1.0 mL of the solution, including the sodium hyaluronate, was aspirated before wound closure. The next day, the intraocular pressure OD was elevated to 60 mmHg, and it remained high despite medication. Three days later, the intraocular pressure was still high, a paracentesis was done, and viscous solution was obtained. After the paracentesis, the intraocular pressure OD normalized. PMID- 8198362 TI - Risk factors for herpes simplex-induced keratitis: a case-control study. AB - Forty-two patients at three institutions were compared with control subjects with regard to the prevalence of risk factors for herpes simplex-induced keratitis (HSK) that have been postulated in the literature. The patients' average age was 46.3 years; their average age at the first episode of HSK was 41.7 years. Seventy five percent of the patients had recurrent HSK. The infection was bilateral in 11.76% of the patients. There was no seasonal variation in the onset of HSK. Furthermore, there was no statistical association between HSK and male sex, atopy, corticosteroid use, intraocular trauma, contact lens wear, or herpes labialis infection. This pilot study raises issues regarding the design of future investigations of the epidemiology of this infection. PMID- 8198363 TI - Metallic foreign body in the orbit. AB - We present an unusual case of a large metallic object penetrating the orbital floor. Early exploration and extirpation of the foreign body improved the restricted eye movements. The treatment and complications of orbital foreign bodies are discussed. PMID- 8198364 TI - Intermittent diplopia in chordoma. AB - The symptoms and findings of three patients with clivus chordomas who had episodes of intermittent diplopia are presented. The causes of intermittent diplopia are reviewed, and the possible mechanisms of this symptom in chordomas are discussed. PMID- 8198365 TI - Discrete and confluent Lisch nodules in neurofibromatosis type 1. AB - Discrete and confluent iris hamartomas in a 42-year-old man with neurofibromatosis type 1 is reported. PMID- 8198366 TI - Photochromatic intraocular lens (IOL) PMID- 8198367 TI - Photoreceptor dysfunction in central areolar choroidal dystrophy. AB - Central areolar choroidal dystrophy (CACD) is a rare, bilateral, autosomal dominant macular dystrophy. Early in the course of the dystrophy, there is fine, symmetric mottling of the retinal pigment epithelium in the macula, often in a bull's-eye pattern. This progresses to geographic atrophy of the macula without noticeable drusen or flecks. This article describes the funduscopic, angiographic, and electrophysiologic findings in three patients with three generations of a pedigree with CACD. Generalized photoreceptor dysfunction was present in the oldest patient and manifested by delayed electroretinographic implicit timing. Age-related generalized photoreceptor abnormality is hypothesized in CACD. PMID- 8198368 TI - A physical model demonstrating Schachar's hypothesis of accommodation. AB - Schachar's hypothesis of accommodation states that there is increased zonular tension during accommodation and the observed in vivo changes in lenticular curvature that occur during accommodation are the result of zonular forces. To demonstrate that there can be steepening of the central curvature of the lens with increased zonular tension, profile photographs of an equatorially unstretched and stretched gelatin-filled balloon and profile photographs from the literature of an unstretched and equatorially stretched human lens were digitized. Their radii of curvature were determined. We found that equatorial stretching of both the gelatin-filled balloon and the human lens produced central curvature steepening that was consistent with Schachar's hypothesis of accommodation. PMID- 8198369 TI - The role of oncogenes in hematologic malignancies. AB - Oncogenes are activated forms of cellular genes involved in normal cell growth and development. Some oncogenes play a role in human malignancies. In hematologic malignancies, researchers have identified many transcription factors as oncogenes based on one of the following criteria: their association with transforming retroviruses in animals, their translocation into either the immunoglobulin or T cell receptor loci, or the production of fusion proteins resulting from chromosomal translocations. The molecular characterization of oncogenes in hematologic malignancies has led to the discovery of new methods for diagnosis and detection of minimal residual disease. In the future, researchers probably will develop novel treatment strategies to interfere with the function of these oncogenes. PMID- 8198370 TI - Collagenous colitis and lymphocytic colitis. AB - Collagenous and lymphocytic colitis are newly recognized causes of chronic watery diarrhea that typically affect middle-aged patients. Although endoscopic studies are normal, inflammatory changes and (in the case of collagenous colitis) collagen deposition occur histologically in the colonic mucosa. The pathogenesis of these disorders remains a mystery, but the possible causes are intriguing. Patients may experience spontaneous remissions and relapses, but treatment with sulfasalazine or prednisone is usually effective for patients with distressing symptoms. PMID- 8198371 TI - Neuromuscular control of the oropharynx and esophagus in health and disease. AB - The oropharynx and esophagus convey swallowed materials from the mouth to the stomach and protect the airways from aspiration. These functions are subserved by complex neuromuscular interactions that coordinate the timing of the peristaltic contractions of the swallowing organs. The oropharynx and upper esophagus are composed of striated muscle, whereas the distal esophagus is composed of smooth muscle. The central nervous system completely controls peristalsis in the striated muscle organs. In the distal esophagus, neuromuscular mechanisms intrinsic to the esophagus control peristalsis. Diseases of the striated muscle, of the smooth muscle, or of the nervous system can lead to a derangement of peristalsis and disrupt the propulsion of swallowed materials to the stomach. PMID- 8198372 TI - Transplantation of the heart and lungs in children. AB - Heart transplantation in children with complex congenital heart disease or cardiomyopathies has become an effective form of therapy for patients with no other surgical options. Because pediatric pulmonary transplantation is a relatively new procedure, long-term follow-up data are not yet available. However, the intermediate-term results of pediatric lung transplantation appear similar to those for heart and lung transplantation. Children represent a particularly difficult patient group for transplant of thoracic organs, and recipients must be selected carefully. Additionally, physicians must pay close attention to multiple medical conditions relating to the underlying disease process in order to achieve optimal results. PMID- 8198373 TI - Molecular basis of hereditary disorders of connective tissue. AB - The molecular basis for several hereditary disorders of connective tissues has been elucidated in recent years. In this chapter, we discuss recent advances in the molecular characterization of a number of these disorders and examine their clinical applications. PMID- 8198374 TI - Hirudin: clinical potential of a thrombin inhibitor. AB - Hirudin is the most potent and specific known inhibitor of thrombin, the enzyme that plays a key regulatory function in hemostasis and blood coagulation. The importance of thrombosis in cardiovascular disease has recently highlighted the limitations of existing antithrombotic drugs and the potential value of direct thrombin inhibition as an effective approach to antithrombotic therapy. Hirudin and a small peptidomimetic analog--hirulog--are being developed as alternatives to heparin for the treatment of unstable angina, for prevention of abrupt closure and restenosis following coronary angioplasty, for prevention of deep vein thrombosis after major orthopedic surgery, and as an adjunct to fibrinolytic therapy. Direct thrombin inhibitors have several potential advantages over heparin: They can inhibit thrombin bound to clots or extracellular matrices, which are relatively resistant to heparin; they do not require antithrombin III as a cofactor, which may lead to a more predictable dose response; and they are not inhibited by activated platelets, which release platelet factor 4 and other molecules that neutralize heparin. The results of early clinical studies suggest that hirudin and hirulog may be more efficacious and more predictable and may have fewer bleeding complications than heparin for several clinical indications. PMID- 8198375 TI - Cellular and molecular abnormalities in the vascular endothelium of diabetes mellitus. AB - Diabetic vascular complications affect both micro- and macrovasculature, primarily in the retina, renal glomeruli, and multiple sites in the macrovessels. This review presents a summary of the abnormal function found in vivo and in cultured vascular cells exposed to elevated levels of glucose. We also discuss the various biochemical hypotheses that have been proposed to explain the adverse effects of hyperglycemia on vascular cells. PMID- 8198376 TI - Hypercalcemia of malignancy: the central role of parathyroid hormone-related protein. AB - Hypercalcemia is the most common metabolic complication of cancer. Malignancy associated hypercalcemia (MAHC) can be divided into two syndromes, humoral hypercalcemia of malignancy (HHM) and local osteolytic hypercalcemia (LOH), based on whether a circulating hormone or local paracrine factors mediate accelerated bone resorption. Over the past decade, studies have shown that parathyroid hormone-related protein is the cause of the HHM syndrome, and recent data suggest that this protein may also play a paracrine role in some patients with local osteolytic hypercalcemia. Study of the regulation of parathyroid hormone-related protein gene expression is beginning to shed some light on the molecular mechanisms responsible for this common clinical problem. PMID- 8198377 TI - Nonrenal complications of the nephrotic syndrome. AB - The nephrotic syndrome is a consequence of urinary loss of intermediate-sized plasma proteins and the resulting homeostatic responses to those losses. Plasma protein composition is changed greatly. Pathophysiologic changes are a consequence of the nature of the proteins lost and of the proteins that are increased in plasma to replace them. Plasma oncotic pressure (pi) falls because of the replacement of relatively small plasma proteins by larger ones. Decreased pi increases transudation of fluid into the interstitium and favors edema. This is exacerbated by causing renal insensitivity to atrial natriuretic factor (ANF), primary renal sodium retention, and plasma volume expansion. Many proteins lost in the urine, such as erythropoietin and IgG, are not defended by increased synthesis. Their loss may result in reduced immunity, anemia, and endocrinopathies. Albumin synthesis can be increased by dietary protein augmentation; however, urinary protein losses also increase, offsetting any palliative effect of increased albumin synthesis on albumin stores. The synthesis of many other proteins secreted by the liver is also increased, causing an elevation in plasma levels of several large proteins, including lipoproteins and elements of the coagulation cascade. This results in hyperlipidemia and, in conjunction with the urinary loss of smaller proteins that impede coagulation, a hypercoagulable state. Lipoprotein catabolism is also reduced as a consequence of proteinuria contributing to increased lipid levels. PMID- 8198378 TI - Thalassemia: pathophysiology of red cell changes. AB - The thalassemias are extremely heterogeneous in terms of their clinical severity, and their underlying pathophysiology relates directly to the extent of accumulation of excess unmatched globin chains: alpha in beta thalassemia and beta in the alpha thalassemias. However, the accumulation of each separate globin chain affects red cell membrane material properties and the state of red cell hydration very differently. These observations presumably account for the varying extent of ineffective erythropoiesis and peripheral blood hemolysis in the major variants of thalassemia. The thalassemias are a worldwide group of inherited disorders of globin-chain synthesis that developed in multiple geographic regions, probably because they provided partial protection against malaria. In normal assembly of adult hemoglobin (HbA-alpha 2 beta 2), alpha and beta globin are synthesized by genes on different chromosomes, whereas heme is synthesized primarily on mitochondria. The synthesis of these chains is very tightly coordinated so that the ratio of alpha globin to beta globin (beta in this case including the beta-like globins delta and gamma) is normally 1 +/- 0.05. Furthermore, specific erythroid proteases are designed to attack and destroy excess alpha or beta globin chains, demonstrating the deleterious impact of the accumulation of excess unmatched globin chains. In beta thalassemia, production of beta globin decreases and excess alpha globin accumulates. In alpha thalassemia, on the other hand, this process occurs in reverse. Perhaps in these disorders more than any others, molecular biologists have documented the deletional and transcriptional events leading to diminished synthesis of specific classes of globin chains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198379 TI - Natural history of autosomal dominant polycystic kidney disease. AB - At least two different genes, which have been mapped to chromosomes 4 and 16, cause autosomal dominant polycystic kidney disease, a disorder with renal and extrarenal manifestations. Although gene-linkage testing is possible, the disease is diagnosed mainly through ultrasonography. Renal disease is characterized clinically by hypertension, acute and chronic pain, and variable progression to end-stage renal disease. Extrarenal manifestations include liver cysts, which may lead to complications; ruptured intracranial aneurysms; cardiac valvular disease; colonic diverticula; and inguinal hernias. Disease management is directed at minimizing and treating the complications of this illness. PMID- 8198380 TI - Diet and nephrolithiasis. AB - Pharmacologic therapy of recurrent nephrolithiasis continues to be the mainstay of the strategy to prevent recurrence. This approach persists even in the face of increasing evidence of a marked benefit of mere entry into a nonpharmacologic diet and fluid modification protocol at a clinic specializing in the evaluation and therapy of recurrent nephrolithiasis (the "Stone Clinic effect"). This review examines the role of diet in the pathogenesis of various forms of nephrolithiasis and the effectiveness of dietary therapy in preventing new stone formation. Recent and older evidence support a primary role for modification of diet, particularly diet protein and sodium intake, in the prevention of recurrent nephrolithiasis. PMID- 8198381 TI - Metabolic interactions of diabetes and pregnancy. AB - Many of the embryonic and fetal abnormalities that occur in pregnancies complicated by maternal diabetes are the result of development in a metabolically abnormal environment. Diabetic embryopathy (birth defects and spontaneous abortions) results from maternal metabolic abnormalities during the first 6-7 weeks of gestation. The embryopathy appears to be multifactorial in origin, and the resulting defects remain important causes of morbidity and mortality in diabetic pregnancies. Diabetic fetopathy (predominantly macrosomia and neonatal hypoglycemia) results from fetal overnutrition and hyperinsulinemia during the second and third trimesters. Fetopathy may cause significant morbidity not only in the perinatal period, but also in later life as overweight infants grow up to be overweight children and young adults. Careful regulation of maternal metabolism from the preconceptional period onward can reduce greatly or even eliminate the excess risks that have been incurred by infants of diabetic mothers in the past. Successful management of maternal diabetes requires knowledge of the alterations in intermediary metabolism that normally occur during pregnancy, as discussed in this chapter. PMID- 8198382 TI - Pathogenesis and host response in Pneumocystis carinii pneumonia. AB - Pneumocystis carinii (PC) pneumonia is recognized as the leading cause of opportunistic pulmonary infections in immunocompromised hosts during the past decade. Although much remains unknown about pathogenesis and host response in PC, recent years, studies of PC have provided us with an increasing base of knowledge about this organism and its relationship to the host. These studies have led to a better understanding of mechanisms of PC attachment and injury to host cells. New information about the interaction of PC with pulmonary surfactant provides insight about the pathophysiology of PC pneumonia. The interplay of the organism, host inflammatory cells, release of cytokines, generation of toxic metabolites, and involvement of both cellular and humoral immunity is complex, but understanding the pathogenesis of PC pneumonia is necessary in order to develop new therapies for this disorder. PMID- 8198383 TI - The present use of electroconvulsive therapy. AB - Physicians attempting to treat certain severe mental disorders have recently shown renewed interest in electroconvulsive therapy (ECT). A number of technical innovations have made ECT safer, as well as more effective. These innovations include oxygenation, muscular relaxation, unilateral nondominant electrode placement, use of brief-pulse stimuli, titrated stimulus dosing, electroencephalographic (EEG) monitoring, determination of seizure adequacy, and pharmacologic enhancement of treatment response. PMID- 8198384 TI - Malaria, the red cell, and the endothelium. AB - Erythrocytes infected with mature stages of Plasmodium falciparum malaria adhere to vascular endothelial cells in postcapillary venules of several organs. In some patients, infected cells also form rosettes with uninfected erythrocytes. The special pathology of acute cerebral malaria appears to result from excessive adherence of infected cells in cerebral vessels coupled with occlusion of cerebral blood flow in microvessels by infected cell rosettes. Several endothelial cell proteins have been identified as potential receptors for infected erythrocyte adherence to vascular endothelium, including thrombospondin, CD36, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). The receptor on infected erythrocytes that mediates adhesion to endothelial cells has been identified as a very large malarial protein on infected cells called PfEMP1. PfEMP1 has been shown to bind to CD36 and thrombospondin in vitro. Antibody mediated blockade or reversal of infected erythrocyte adherence to vascular endothelium is postulated not only to decrease the pathology of blood-stage malaria, but also to lead to infected cell destruction and clearance, especially in the spleen. PfEMP1 is therefore a prime candidate malarial protein for inclusion in a multicomponent asexual malaria vaccine. PMID- 8198385 TI - Molecular events in the pathogenesis of hepadnavirus-associated hepatocellular carcinoma. AB - Chronic hepadnavirus infection is associated with hepatocellular carcinoma (HCC) in natural hosts such as humans, woodchucks, and Beechey ground squirrels. Several possible oncogenic mechanisms have been identified, including a potential role of the hepadnavirus x (hbx) gene, which transactivates transcription regulated by certain cis-acting sequences, e.g. regulatory sequences of the hepatitis B virus (HBV) and heterologous regulatory sequences of other viruses and cellular genes. The oncogenic potential of hbx is suggested by the observation of HCCs in hbx transgenic mice, the oncogenic transformation of cells expressing hbx in culture, and the transactivation of oncogenes c-myc and c-jun by hbx. Cis-activation of cellular oncogenes N-myc and c-myc by viral promoter insertion has been a common finding in woodchuck hepatitis virus (WHV)-associated HCCs of woodchucks. No such cis-activation of any cellular gene has been shown in virus-associated HCCs of ground squirrels or humans. Amplification and overexpression of the c-myc gene has been a common finding in HCCs of ground squirrels, and is rare in woodchuck or human HCCs. Point mutations in the p53 gene and allelic deletion of p53 have been common findings in human HCCs, but have not been found in HCCs in woodchucks and have been found rarely in ground squirrels. How each of these genetic changes in the different hosts contributes to HCC remains to be determined, but apparently different changes in different HCCs of hepadnavirus-infected hosts suggest that several separate genetic events may contribute to the development of HCC. These events may differ in each host, and some may not result from a direct virus-specific mechanism. Chronic hepadnavirus infection is often associated with chronic necroinflammatory liver disease and cirrhosis, a pathologic process common to several other risk factors for HCC. This suggests that this pathologic process (necroinflammatory disease) may be hepatocarcinogenic regardless of the inciting agent. Thus hepadnavirus infection may play an important role in the development of HCC by causing chronic hepatitis and HCC with the same mechanisms by which other risk factors for HCC cause chronic necroinflammatory liver disease and HCC. PMID- 8198386 TI - The earliest diagnosis of acute myocardial infarction. AB - Acute myocardial infarction results from the cessation of myocardial blood flow caused by thrombotic occlusion of a coronary artery. Rapid restoration of blood flow to the ischemic myocardium minimizes cardiac damage and improves early and long-term morbidity and mortality. Chest pain is the first symptom of myocardial infarction, but in some patients with silent ischemia, the disease can be diagnosed only in retrospect. In symptomatic patients, myocardial infarction should be accurately and promptly diagnosed so that reperfusion therapy can begin immediately. Electrocardiography is the simplest diagnostic modality. Although regional ST-segment elevation is specific, it is not sensitive. In contrast, new computerized algorithms for electrocardiographic analysis and serial monitoring increase sensitivity without decreasing specificity. In the emergency room, echocardiography is used to diagnose patients with no prior history of coronary artery disease whose electrocardiograms proved nondiagnostic. Time-consuming perfusion nuclear studies are inferior to echocardiography but may nevertheless enable physicians to diagnose myocardial infarction in the emergency room. Although the presence of excess creatine kinase is a sign of myocardial necrosis, its increase is delayed for a few hours after coronary occlusion. Doctors can diagnose myocardial infarction as early as two hours after coronary occlusion with the help of simpler automatic assays of MB-creatine kinase mass that use monoclonal antibodies. Other investigational markers of myocardial necrosis include myoglobin and troponin. Elevation of a circulating protein marker also signifies established necrosis, but physicians hope to achieve reperfusion through therapy before irreversible damage occurs. PMID- 8198387 TI - Factors affecting outcome after recovery from myocardial infarction. AB - Patients surviving acute myocardial infarction are susceptible to heart failure, recurrence of angina, reinfarction, arrhythmias, and sudden cardiac death. Most deaths occur in the first six months after infarction. Advancing age is the most important nonmodifiable prognostic factor for long-term prognosis, whereas left ventricular function assessed clinically or measured as either ejection fraction or end-systolic volume is the most important modifiable factor. Other significant long-term prognostic factors include: postinfarction angina at rest, inducible ischemia during exercise testing with or without radioisotope imaging, severity and extent of coronary artery disease, patency of the infarct-related artery, late ventricular arrhythmias, decreased heart rate variability, cigarette smoking, hypercholesterolemia, and diabetes mellitus. Identification of these adverse prognostic factors permits risk stratification and enables physicians to determine the most appropriate and cost-effective treatment. Most patients should have a stress test for inducible ischemia and a non-invasive (echo or radionuclide) assessment of left ventricular function. For high-risk patients such as those with prior infarction, heart failure, early postinfarction angina, or frequent late ventricular arrhythmias, coronary angiography and ventriculography prior to discharge are recommended. Assessment of late potentials and heart rate variability will help identify a subgroup of patients at risk for ventricular arrhythmias and cardiac death. However, a more accurate prediction of reinfarction is not possible at present, and no reliable test for atherosclerotic plaque instability has been developed. PMID- 8198388 TI - Prognosis in congestive heart failure. AB - Prognostic variables such as the ejection fraction and peak oxygen consumption can be used to place patients with heart failure in risk strata. Some vasodilators have been shown to improve survival at all stages of heart failure with the probability of benefit increasing as the prognosis worsens. Quantitative estimates of survival among groups defined by prognostic variables and treatments should be used to make more informed benefit-to-risk assessments. PMID- 8198389 TI - Mechanism of epilepsy. AB - Epilepsy is a collection of diverse disorders that together affect approximately 1% of the general population. Current therapies are largely symptomatic and are aimed at controlling seizures in affected individuals. This review focuses on emerging insights into mechanisms underlying the most common form of epilepsy- complex partial epilepsy--and also addresses progress in molecular genetic approaches. Such developments will hopefully lead to more effective therapies. PMID- 8198390 TI - Gonadotropin-releasing hormone and its analogs. AB - GnRH and its analogues have led to exciting new avenues of therapy in virtually every subspecialty of internal medicine as well as in gynecology, pediatrics, and urology. Since their discovery in 1971, it has been demonstrated that GnRH and its analogues enable medical professionals to influence the hypothalamic pituitary-gonadal axis in two distinct classes of therapeutic applications. The first provides natural sequence GnRH in a pulsatile fashion via portable infusion pumps to mimic the normal physiology of hypothalamic GnRH secretion and restores reproductive potential to infertile men and women with disorders of endogenous GnRH secretion. The second mode uses long-acting GnRH agonists administered in a depot delivery to produce a paradoxical desensitization of pituitary gonadotropin secretion which, in turn, results in a complete ablation of the reproductive axis. This biochemical castration induced by GnRH agonist administration is a safe, effective, complete, and reversible method of removing the overlay of gonadal steroids from a variety of diseases which they are known to exacerbate. These diseases include endometriosis and uterine fibroids in women, prostate cancer in men, and precocious puberty in both sexes. This review examines the physiologic and pharmacologic principles underlying the advances produced by these agents, the mechanism of action of GnRH and its analogues at the cellular level, and the individual therapeutic applications to which these analogues have been applied. Because virtually every subspecialty of medicine will be touched by the GnRH analogues, this review provides an overview and background of their use. PMID- 8198391 TI - Use and abuse of human growth hormone. AB - Recombinant human growth hormone (hGH) has been available for nearly a decade. Side effects are rare. Its efficacy in promoting growth acceleration has been widely confirmed in children with GH deficiency (GHD), Turner syndrome, idiopathic short stature, chronic renal failure, and a variety of other conditions. The dramatic increase in height velocity in the first year of therapy partially attenuates in subsequent years in all patient groups, and convincing final height data are only available in GHD and Turner syndrome. Pediatric endocrinologists continue to be troubled by definitions of GHD. Although profound GHD is relatively obvious, other patients with severe growth failure but borderline or normal endocrine testing also respond to hGH therapy. Thus many endocrinologists use auxologic criteria [e.g. low growth velocity, height < -3 standard deviation (SD), poor predicted adult height] as the de facto basis for therapy, leading to a blurred distinction between treatment of disease and enhancement of normal characteristics and, finally, raising questions about the ultimate benefit of hGH therapy. Brief clinical trials of hGH therapy in adults both with and without GHD have reported increased muscle mass, decreased fat, and improvement in quality of life. Internists may soon be faced with treatment decisions analogous to those confronting pediatricians, i.e. whether to use hGH to repair aspects of the normal aging process. PMID- 8198392 TI - Modulation of the ionic milieu of the airway in health and disease. AB - Airway surface liquid (ASL) is an integral part of lung defense mechanisms. Ion transport by airway epithelia regulates the volume and composition of this fluid. A better understanding of the mechanisms of ion transport will enable the development of new therapies for airway diseases associated with defects in these mechanisms. A useful model of a disease with abnormal airway epithelial ion transport is cystic fibrosis (CF), a distinct genetic syndrome of altered lung defense mechanisms characterized by chronic bacterial infection and a steady decline in lung function. Traditional therapies for CF include antibacterial drugs and augmentation of clearance of secretions, but investigators are now studying pharmacological approaches to target the more basic defect of the disease, i.e. abnormal sodium and chloride ion transport. Early treatment in childhood, prior to lung damage, might prevent or at least retard the decline in pulmonary function that remains the hallmark of CF. Ion transport dysfunction may also contribute to other airway diseases such as asthma and chronic bronchitis. Pharmacological intervention at this level may prove beneficial in these common lung diseases as well. PMID- 8198393 TI - Cellular and molecular biology of Alzheimer's disease and animal models. AB - Alzheimer's disease (AD), the most common dementing disorder of late life, is a major cause of disability and death in the elderly. Neurobiological, genetic, and molecular studies have defined the vulnerable neural systems, abnormalities in cytoskeletal proteins in neurons, the biology of the beta-amyloid precursor protein (APP) and beta-amyloid (A beta, beta A4), and several APP mutations linked to the disease. More recently, investigators have begun to develop animal models essential for delineating pathogenetic mechanisms and for developing and testing new therapies for treating AD in humans. This review focuses primarily on recent progress in investigation of animal models of AD (including aged nonhuman primates and transgenic mice), which have begun to clarify some of the questions raised by investigation of the disease in humans. PMID- 8198394 TI - Antidepressants in long-term treatment. AB - One of the most important recent developments in the management of depression is the recognition of the need for long-term treatment. Treatment of an episode of depression must continue after apparent response in order to consolidate response and prevent relapse. A continuation treatment period of at least four months after response of the acute episode is required in all patients with depression. Most depression is recurrent, and prophylactic treatment with antidepressants reduces the risk of new episodes. This treatment needs to be continued over very long periods, because the risk of new episodes does not appear to diminish with time. In selecting an antidepressant for long-term treatment efficacy, safety and tolerability in the long term should be taken into account since not all antidepressants have been adequately tested, and some do not appear to be effective. The most thoroughly tested antidepressants are the tricyclic imipramine and the new selective serotonin reuptake inhibitors. PMID- 8198395 TI - Molecular genetics of human thyroid neoplasms. AB - Cancers are thought to develop as a result of sequential mutations of genes important in the control of cellular growth. Recently investigators identified a number of genetic defects that affect oncogenes and tumor-suppressor genes and that provide insight into the biology of benign and malignant thyroid neoplasms. Future implications for thyroid tumor diagnosis and prognosis are considered in this chapter. PMID- 8198396 TI - Strategies for attenuating protein-catabolic responses in the critically ill. AB - Specialized enteral and parenteral nutrition are now a standard components of care in critically ill patients. This adjunctive therapy corrects and prevents nutrient deficiencies, attenuates the loss of body protein, and improves clinical outcomes in malnourished patients. Several novel strategies designed to improve the metabolic and clinical effects of specialized nutrition are under vigorous clinical investigation. These new approaches include increased emphasis on enteral feeding to maintain intestinal absorptive, immune, and barrier function; administration of conditionally essential amino acids (glutamine, arginine); use of specialized lipid products and antioxidants; and administration of growth factors such as human growth hormone. Randomized, controlled clinical trials will define the clinical and metabolic efficacy and cost-effectiveness of these therapies in specialized nutrition support. PMID- 8198397 TI - Inflammatory heart disease: pathogenesis, clinical manifestations, and treatment of myocarditis. AB - Myocarditis is an uncommon cause of cardiac disease that can result in arrhythmia, congestive heart failure, and death. Myocardial injury in myocarditis is due in part to activated cellular and humoral immune components directed toward normal cardiac tissue. Although numerous therapies for myocarditis, including corticosteroids and immunosuppressive agents, have been applied in animal experiments and in human studies, none have demonstrated survival benefit over untreated controls. In many patients, myocarditis may spontaneously resolve. Information about myocarditis pathogenesis, manifestations, and treatment has been useful in disease management. Further research into the inflammatory nature of myocarditis may provide the basis for more favorable outcomes of intervention in this disease. PMID- 8198398 TI - Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. AB - Advances in the molecular biology of human diseases indicate that the most striking manifestations of illness may be caused not by exogenous pathogenic or tumor products, but rather by toxic peptides produced by the host itself. Tumor necrosis factor (TNF), a polypeptide cytokine produced during infection, injury, or invasion, has proved pivotal in triggering the lethal effects of septic shock syndrome, cachexia, and other systemic manifestations of disease. Because removing TNF from the diseased host may prevent development of the illness, this factor has recently been the focus of intensive research. This review discusses the biology of this cytokine, with particular emphasis on its potential therapeutic role in septic shock and cachexia. PMID- 8198399 TI - Male sex determination: current concepts of male sexual differentiation. AB - In order for an infant to develop as a phenotypically complete male or female, a cascade of complex molecular and morphological events must occur at the appropriate time and in the correct sequence during ontogeny. The male embryo's genetic sex is determined by its chromosomal constituents, the most important of which is the sex-determining gene, or testis-determining factor (TDF), on the Y chromosome. Male gonadal sex, or testis formation, is subsequently thought to be determined by this gene and by other secondary pathways. The male gonad, in turn, normally produces hormones such as testosterone and Mullerian inhibiting substance (MIS) that regulate differentiation of the internal and external genitalia, thus determining phenotypic sex. When an abnormality develops in any of the above three processes, an intersex infant with ambiguous genitalia results from the incongruent genetic, gonadal, and phenotypic sex. Clinically, such 46XY males with intersex abnormalities present challenges for gender assignment, timely surgical intervention, and appropriate hormonal therapy. PMID- 8198401 TI - Therapy of carotid arteriosclerosis. AB - Carotid arteriosclerotic disease is the most readily treatable type of lesion leading to stroke. Its management involves lowering those risk factors over which the patient has control. Patients should regulate hypertension, quit smoking, seek medical attention for treatable cardiac abnormalities, and take steps to reduce increased blood lipids. For symptomatic carotid disease, regardless of whether surgery is offered, platelet inhibitors are obligatory. The recommended dose is 650 mg aspirin per day (or up to 1300 mg, if tolerated). For patients whose symptoms continue despite aspirin therapy or who are aspirin intolerant, ticlopidine is the only recommended platelet inhibitor. Cerebral arterial bypass surgery is not an effective treatment for carotid arteriosclerosis. Carotid endarterectomy helps patients with > or = 70% stenosis as determined by strict arteriographic measurements. We do not yet have sufficient data to determine whether endarterectomy would benefit patients with lower levels of carotid stenosis or asymptomatic patients with any degree of stenosis. PMID- 8198400 TI - The course and treatment of lupus nephritis. AB - Renal involvement by systemic lupus is variable; some patients have minimal clinical and histologic involvement, whereas others have fulminant renal failure and severe proliferative renal lesions on biopsy. The World Health Organization (WHO) classification has greatly aided in the study of lupus nephritis. This classification defines six major patterns of renal involvement, each with characteristic clinical correlates and a typical course and prognosis. Transformations from one pattern of lupus nephritis to another may occur, and there may also be prominent involvement of the tubulointerstitial compartment and vasculature. Treatment of the renal lesions may be directed at the individual class of lupus nephritis. Thus patients with mesangial involvement (WHO Class II) do not require therapy directed at their kidney lesions. Many patients with biopsies showing focal proliferative disease (WHO Class III) and all patients whose biopsies show diffuse proliferative lesions (WHO Class IV) require vigorous treatment, which has included high-dose daily and alternate-day corticosteroids, azathioprine, i.v. pulse methylprednisolone, plasmapheresis, total lymphoid irradiation, cyclosporine, and oral and i.v. cyclophosphamide. Controlled trials have yielded reasonable evidence for the safety and efficacy of some treatments, whereas others have been used only in uncontrolled studies. When used judiciously, such vigorous therapy can improve the renal survival of patients with severe lupus nephritis. PMID- 8198402 TI - Monoclonal proteins and renal disease. AB - Renal insufficiency, which is present initially in almost half of patients with multiple myeloma, usually results from myeloma kidney or hypercalcemia. Neither the class of light chain nor the isoelectric point plays an important role in kidney failure. Acute renal failure must be treated with appropriate fluids and with electrolytes and hemodialysis if necessary. Plasma exchange may be helpful, but has not been proven as such. The presence of a nephrotic syndrome and a monoclonal kappa or lambda light chain in the urine almost always indicates primary amyloidosis (AL) or light-chain deposition disease. Amyloid fibrils must be distinguished from the fibrils of immunotactoid glomerulopathy. PMID- 8198403 TI - Enzymatic synthesis of butyryl-rutin ester in organic solvents and its cytogenetic effects in mammalian cells in culture. AB - Enzymic acylation of a flavonoid, rutin, with trichloroethylbutyrate (TCEB) has been performed by subtilisin protease in anhydrous pyridine solution. The addition of a hydrophobic compound on rutin is expected to change the hydrophilic/hydrophobic balance of the molecule, giving new properties to this compound. This work aimed at investigating the various cytological properties of the rutin-ester and compared them with those of the native molecule. No difference in the levels of sister chromosomes exchange (SCE) between rutin and rutin-ester treated cells at doses varying from 25 to 200 micrograms/mL was found. On the contrary impressive difference in the induced frequency of micronuclei (MN) between rutin and rutin ester treated cells was observed, for example, at a dose of 100 micrograms/mL of rutin were 3.5% MN counted, whereas for a similar dose treatment with rutin-ester a frequency of 8% of MN was found. The fact that rutin-ester is causing significantly higher levels of MN than the rutin alone can be considered as a manifestation of a higher action of the agent on the chromosome owing to its easier penetration in to the cell after its esterification. PMID- 8198404 TI - Contribution to the study of the alteration of lipase activity of Candida rugosa by ions and buffers. AB - A semipurified C. rugosa lipase (LS) has been prepared from commercial lipase (LC) using an economical procedure. The presence of sugars and glycopeptides has been detected in LS and LC. Pure lipase only has covalently bonded sugars. The hydrolysis of olive oil catalyzed by LS and commercial lipase (LC) is sensitive to the presence of cations Na(I), Mg(II), Ca(II), and Ba(II) and to the nature of buffer. Highest enzyme activity is obtained with 0.1M Tris/HCl buffers and the combination of NaCl 0.11M and CaCl2 0.11M. Fluorescence spectroscopy analysis of LC, LS, and both pure isoenzymes lipases A and B, was used to analyze the interaction of the lipase with these effectors. Inorganic cations Na or Ca do not interact with pure enzyme LA but do interact with LC and LS and do so slightly with LB. The organic cations (morfolinium or tris) interact with pure lipases. We postulate that the increase in the lipase activity produced by Na(I) or Ca(II) is related with interfacial phenomena, but the increase might be more specific in the hydrolysis of olive oil in the presence of Tris-HCl or morfoline-HCl buffer, owing to enzyme-buffer interaction. PMID- 8198405 TI - Xylanolytic enzyme production by an Aspergillus niger isolate. AB - Production of xylanolytic enzymes by an Aspergillus niger CCMI 850 isolate was investigated in batch cultures. The effect of the composition of a fermentation medium that did not include chemical inducers, on beta-xylanase, beta-xylosidase, alpha-L-arabinofuranosidase, and total cellulase activity was studied. With 4% xylan as the carbon source, about 65 U/mL of beta-xylanase was obtained, whereas the total cellulase activity was undetectable, under the specified conditions. This beta-xylanase activity represents the highest reported for a wild-type strain of A. niger. The effect of pH and temperature on the activity of beta xylanase was studied. Partial characterization of the beta-xylanase showed that with insoluble birchwood as substrate the Km and Vmax were 0.3 mM and 19 mumol/min, respectively. Aspects of using the crude beta-xylanase preparation for applications in the pulp and paper industry were discussed. PMID- 8198406 TI - Fetoplacental circulation in health and disease. PMID- 8198407 TI - The TORCH screen and intrauterine infections. PMID- 8198409 TI - Behavioural response to pain in healthy neonates. AB - A bedside technique for evaluating the behavioural response of healthy neonates to pain was assessed. Thirty six term infants (median gestational age 40 weeks; median postnatal age 4 days) and 31 preterm infants (median gestational age 34 weeks; median postnatal age 4 days) were assessed at the cotside for their response to heel preparation and heel lance for routine blood sampling. The facial actions of brow bulge, eye squeeze, nasolabial furrow, and open mouth were noted, and also the presence or absence of crying. Thirty five (97%) term and 26 (84%) preterm infants showed an increase in the number of behaviours in response to heel lance. Brow bulge and nasolabial furrow were seen most often, and occurred more often than crying in the two groups. There was good interobserver agreement (94%). The consistency of response and the high degree of interobserver agreement makes this method of behavioural assessment of acute pain of use in healthy neonates. PMID- 8198408 TI - Cerebral autoregulation of preterm neonates--a non-linear control system? AB - The low frequency cerebral blood flow velocity (CBFV) oscillations in neonates are commonly attributed to an under-dampened immature linear type cerebral autoregulation, and the 'instability' is regarded as causative for peri intraventricular haemorrhage/periventricular leukomalacia. In contrast, oscillations susceptible to frequency entrainment are a fundamental part of the stable function of non-linear control systems. To classify the autoregulation an observational study was done on the relationship between CBFV oscillations, heart rate variability, and artificial ventilation. In 10 preterm neonates (gestational age 26 to 35 weeks) we serially Doppler traced arterial CBFV continuously for 12 minutes between days 1 and 49 of life. The individual time series of CBFV and heart rate were subjected to spectral analysis. Forty six of 47 tracings showed significant low frequency CBFV oscillations. Low frequency heart rate oscillations were not a prerequisite thereof. All patients with < 30% of total power in the low frequency band of CBFV oscillations were on the ventilator. Three of them demonstrated a shift of spectral power from low frequency to a frequency equal or harmonic to the ventilator rate indicating entrainment. The findings of CBFV oscillations combined with entrainment classify the autoregulation as a non-linear system. It is suggested that entrainment by periodic high amplitude stimuli might challenge the regulatory capacity to its limits thus increasing the risk for cerebral damage. PMID- 8198410 TI - Alleviation of the pain of heel prick in preterm infants. AB - The hypothesis that the variability of physiological parameters may indicate pain or stress in the neonate was examined. Four parameters (heart rate, respiratory rate, transcutaneous oxygen tension, and carbon dioxide tension) were examined over a 2 minute epoch in response to a heel prick in an attempt to measure stress/pain in 35 preterm newborn infants (26-34 weeks' gestation) half of whom were receiving intensive care. The change in absolute values of these parameters did not discriminate a dummy procedure without prick from the actual procedure containing the prick (paired t test), but the variability of the parameters during an epoch showed significant discrimination. Three procedures were evaluated to reduce this distress using unpaired t test. The use of local anaesthetic cream was not successful. The components of the mixture cause vasoconstriction that would reduce blood flow to the heel and lead to more squeezing which is likely to be painful in the presence of tissue damage. A nurse comforting the infant with tactile and vocal stimulation was slightly helpful but the use of a spring loaded lance was most successful in reducing the distress. The use of spring loaded lances may be more humane for heel pricks. PMID- 8198411 TI - Effect of fresh frozen plasma and gammaglobulin on humoral immunity in neonatal sepsis. AB - Fresh frozen plasma and intravenous immunoglobulin are used as prophylaxis against, and for the treatment of, neonatal infection. It is assumed that any beneficial effect is mediated through the humoral immune factors contained in each preparation. The effect of fresh frozen plasma and intravenous immunoglobulin on humoral immune markers (immunoglobulins and IgG subclasses, complement components and activation products, and C reactive protein) was investigated over a 24 hour period after their randomised administration to 67 infants with suspected infection. Thirty infants without suspicion of infection were studied as controls. Compared with control infants, infants with suspected infection had increased concentrations of C reactive protein, reduced concentrations of fibronectin, and increased concentrations of the complement activation marker C3d, but similar concentrations of IgG, IgG subclasses, IgA, and IgM. After intravenous immunoglobulin treatment (500 mg/kg) concentrations of total IgG and all IgG subclasses increased, as did IgA and complement component C4. Concentrations of C reactive protein decreased after intravenous immunoglobulin treatment and were significantly lower than baseline after 24 hours. In contrast, no change in IgG or IgG subclass concentrations occurred after fresh frozen plasma administration. At 24 hours after fresh frozen plasma administration, concentrations of IgA, IgM, and C4 were significantly higher than baseline and serum IgA was significantly higher than in infants tested 24 hours after intravenous immunoglobulin treatment. These results confirm the rational basis for intravenous immunoglobulin treatment but question the value of fresh frozen plasma, particularly in the light of its attendant problems as an untreated blood product. PMID- 8198412 TI - Development of posture in prone and supine positions during the prenatal period in low risk preterm infants. AB - The development of posture in the prone and supine positions was studied longitudinally in 10 low risk preterm infants between 31 and 39 weeks' postmenstrual age whose subsequent neurological development at 18 months old was normal. The infants were observed from one week after birth until the expected date of delivery. All postures were analysed according to the procedures described by Prechtl et al. There were large intraindividual and interindividual differences in posture in terms of the duration and incidence of the two positions. There was no age specific preferred posture found in either position. The posture duration in the prone position was longer than that in the supine position, but overall flexed and abducted posture were observed more often in the former. Turning of the head to the right side was also observed more often in the prone than in the supine position. PMID- 8198413 TI - Umbilical cord blood erythroblast count as an index of intrauterine hypoxia. AB - The relation of umbilical cord blood arterial pH, Apgar score, leucocyte count, and erythroblast count at delivery with the diagnosis of fetal distress in labour was studied prospectively in three groups of singleton pregnancies delivering at term vaginally (55 infants), by elective caesarean section (39 infants), or by emergency caesarean section for abnormal intrapartum fetal heart rate patterns (55 infants). In the emergency caesarean section group the umbilical cord blood arterial pH was significantly lower and the leucocyte and erythroblast counts were higher than in the elective caesarean section group. Comparison of the emergency caesarean section and spontaneous vaginal delivery groups showed significant differences for pH and erythroblast count, but not for leucocyte count. In the spontaneous vaginal delivery group erythroblastosis was associated with umbilical cord blood pH, whereas leucocytosis was associated with the length of labour. The five minute Apgar score was > or = 7 in all infants. This study suggests that leucocytosis is a non-specific response of the fetus to labour, whereas erythroblastosis reflects fetal tissue hypoxia. PMID- 8198414 TI - The EC randomised controlled trial of prophylactic ethamsylate for very preterm neonates: early mortality and morbidity. The EC Ethamsylate Trial Group. AB - Immature infants are at increased risk of death and disability, often related to haemorrhagic and ischaemic brain damage. Two controlled trials have suggested that a policy of prophylactic ethamsylate may reduce this damage. The aim of the trial reported here was to assess the effects of such a policy in respect of death, disability, and the use of health service resources up to 2 years of age. Short term findings are reported here. Three hundred and thirty four immature (< or = 32 weeks' gestation) infants were recruited into the trial within four hours of birth from four centres in France and six in Greece. Almost all 165 infants allocated to the ethamsylate group received the drug, compared with one of the 169 infants in the control group. By about 3 months of age the trial groups were similar in terms of death (20% in the two groups), any diagnosis of periventricular or intraventricular haemorrhage (35% in the ethamsylate v 37% in the control group), or major cerebral abnormality assessed by ultrasound (13% v 12%). The trial provides little evidence to support the use of ethamsylate for routine prophylaxis. The confidence intervals are wide, however, and so these results alone cannot rule out a clinically useful benefit or a harmful effect. A follow up study of the surviving children at the age of 2 years is in progress. PMID- 8198415 TI - Echocardiographic screening in neonates undergoing surgery for selected gastrointestinal malformations. AB - To compare echocardiography with clinical examination, radiography, and electrocardiography for the detection of congenital heart defects (CHD) a four year prospective study was carried out in 166 neonates with selected congenital gastrointestinal malformations (anorectal anomaly, tracheo-oesophageal fistula, duodenal atresia, exomphalos, and gastroschisis). Routine examination and investigation detected CHD in 16 neonates. Using echocardiography CHD was diagnosed in 38 (23%) neonates of whom five had two gastrointestinal malformations: in 22/57 (39%) with a tracheo-oesophageal fistula, 10/67 (15%) with an anorectal anomaly, 4/20 (20%) with exomphalos, 6/20 (30%) with duodenal atresia, and 1/7 with gastroschisis. A significantly higher incidence of CHD in neonates with gastrointestinal malformations was diagnosed using echocardiography (23%) compared with routine examination and investigation (9%). Early diagnosis of CHD allowed a unified approach to be presented to the family. PMID- 8198416 TI - To PEEP or not to PEEP? AB - It is well recognised that reducing positive end expiratory pressure (PEEP) leads to an increase in the tidal volume and minute volume in ventilated neonates. The magnitude of this effect is perhaps not commonly appreciated, however. Effectively, PEEP is four times as potent as peak inflation pressure (PIP) in bringing about changes in tidal volume. The influence of changes in PEEP and PIP on tidal volume and the relative magnitude of each are considered. Twenty one preterm infants were studied on 38 separate occasions. All were sedated, paralysed, and ventilated, 19 for hyaline membrane disease. A 1 cm H2O reduction in PEEP was twice as potent as a 2 cm H2O increase in PIP in achieving an increase in tidal volume (14 v 7%). Similarly, increasing PEEP by 1 cm H2O was twice as effective as a 2 cm H2O decrease in PIP in reducing tidal volume (13 v 6%). Small (0.5-1 cm H2O) changes in PEEP can often be used to improve ventilation and carbon dioxide elimination. Levels of PEEP of 4-5 cm H2O may, at times, impair gas exchange and contribute to overdistension. PMID- 8198417 TI - Plasma catecholamines after endotracheal administration of adrenaline during postnatal resuscitation. AB - To analyse the degradation of adrenaline after cardiopulmonary resuscitation of preterm neonates, free and sulphoconjugated adrenaline, noradrenaline, and dopamine were determined in 31 preterm neonates by a radioenzymatic method. Nine of the neonates received a high dose (250 micrograms/kg) of endotracheally administered adrenaline (1:1000); three of them had more than one dose of adrenaline. With the exception of sulphoconjugated dopamine, the free and sulphoconjugated catecholamine concentrations in preterm infants treated with adrenaline initially exceeded those in the untreated group. The concentrations decreased to the same range about two hours after birth. Free and sulphoconjugated adrenaline concentrations remained significantly increased in the adrenaline treated group, however, indicating a plateau effect. The correlation between free adrenaline and noradrenaline concentrations with their respective sulphoconjugated concentrations was highly significant. It is concluded that free catecholamines are rapidly degraded by sulphoconjugation in preterm neonates. PMID- 8198418 TI - Bronchodilator aerosol administered by metered dose inhaler and spacer in subacute neonatal respiratory distress syndrome. AB - There is increasing evidence that bronchodilators are effective in ventilator dependent preterm infants. The effects of single doses of salbutamol (400 micrograms), ipratropium bromide (72 micrograms), and placebo (four puffs) given by metered dose inhaler and spacer (MDIS) were examined in 10 ventilated preterm infants, with a mean birth weight of 800 g at a postnatal age of 1 week, who were suffering from respiratory distress syndrome. The agents were each given in an open, random design. Blood gases were measured and ventilatory efficiency index (VEI) and arterial/alveolar oxygen tension ratio (PaO2/PAO2) were calculated five minutes before and 30 minutes after administration. Heart rate and mean arterial blood pressure were noted. The mean PaO2 improved by 0.61 kPa and 0.69 kPa after salbutamol and ipratropium bromide, respectively and these changes were significantly greater than the 0.5 kPa fall seen with placebo. The mean arterial carbon dioxide tension fell by 0.98 kPa after salbutamol and 0.59 kPa after ipratropium bromide. After both salbutamol and ipratropium bromide, VEI improved significantly (by 23% and 20% respectively) but there was no significant change in the PaO2/PAO2, suggesting that respiratory mechanics and not ventilation/perfusion balance had improved after a single dose of bronchodilator. We conclude that both salbutamol and ipratropium bromide given by MDIS have useful short term effects in ventilator dependent neonates with respiratory distress syndrome. Precise dose regimens and long term effects remain to be worked out. PMID- 8198419 TI - Neonatal endothelin-1 concentrations in term infants. AB - Endothelin-1 concentrations were studied in 30 term infants during the first week of life using a radioimmunoassay kit. A neonatal reference range was established (7.5-25.7 pmol/l). No significant relation with age, sex, gestation, or birth weight was found. PMID- 8198420 TI - Unexplained fetal growth retardation: what is the cause? PMID- 8198421 TI - Dr Herbert Barker (1814-1865) of Bedford and infant hygiene. PMID- 8198422 TI - Neonatal respiratory distress syndrome. PMID- 8198423 TI - Patent ductus arteriosus in the newborn. PMID- 8198424 TI - Clinical trials and neonatal intensive care. PMID- 8198425 TI - Early or late parenteral nutrition for the sick preterm infant? PMID- 8198426 TI - An interpretation of toxicity response of bobwhite quail with respect to duration of exposure. AB - Avian dietary toxicity tests were conducted with seven pesticides, two age groups (2 and 16 weeks old) of northern bobwhite (Colinus virginianus) and two durations (5 and 28 days) of exposure. Results were analyzed with an emphasis placed upon comparing mortalities on similar test conditions. An analysis that used the entire dose-time-response results led to the calculation of a common measure (asymptotic rate e) of temporal development of the response surface and served as a basis of comparison of diverse test results. The asymptotic median lethal concentrations were designated by ALC50 and the median lethal concentrations at the end of a test period by LC50. It was found that: (1) Young birds in 5- and 28 day tests were more sensitive to incremental increases in the duration of exposure than adults. (2) Young birds were less sensitive to incremental increases of dietary concentration than adults only in the 5-day test and displayed delayed response patterns in six of seven chemicals in those tests. (3) LC50 values of 5-day tests of young birds were greater than LC50 values of 28-day tests, but the corresponding ALC50s were smaller in 5-day tests than 28-day tests. (4) ALC50s for 28-day tests were lower for young birds than for adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198427 TI - Comparative toxicity of azinphos-methyl to house mice, laboratory mice, deer mice, and gray-tailed voles. AB - A laboratory toxicity study on house mice and laboratory mice (Mus musculus), gray-tailed voles (Microtus canicaudus), and deer mice (Peromyscus maniculatus) was conducted as part of a comprehensive laboratory and field study to field validate laboratory-based risk assessment of pesticides. The single dose oral LD50 for the organophosphorus insecticide azinphos-methyl (Guthion) was 10, 11, 32, and 48 mg/kg body weight in wild house mice, laboratory mice, gray-tailed voles, and deer mice, respectively. Ten-day dietary LC50s were 277 ppm for laboratory mice, 297 ppm for gray-tailed voles, and 1,180 ppm for deer mice. All treated animals lost more weight, consumed less food, and had depressed brain cholinesterase (ChE) activity compared to controls. Five-day LC50s were significantly higher than 10-day LC50s for laboratory mice and deer mice. For all three species, animals that died during dietary LC50 tests had mean ChE activity of 50-55% while survivors had 56-70% of controls. The conclusions were that: (1) Laboratory mice were not representative of deer mice or gray-tailed voles with respect to sensitivity to azinphos-methyl, but provided a conservative estimate for risk assessment; (2) 10-day dietary LC50 tests indicate substantially greater estimates of toxicity of azinphos-methyl to rodents than do 5-day tests; and (3) brain ChE depression of 45-50% was lethal in these species. PMID- 8198428 TI - Prevention of di(2-ethylhexyl)phthalate-induced testicular atrophy in rats by co administration of the vitamin B12 derivative adenosylcobalamin. AB - The administration of 2g/kg of di(2-ethylhexyl)-phthalate (DEHP)-induced severe testicular atrophy coincident with the reduction of testicular specific lactate dehydrogenase (LDH-X) activity, zinc, magnesium, and potassium concentrations in rats. Co-administration of DEHP and adenosyl cobalamin (AdoCbl), one of the active vitamin B12s, prevented these testicular specific changes including fluctuations in testicular weight. On the other hand, co-administration of DEHP and methylcobalamin (MeCbl), the other active vitamin B12, did not prevent the testicular atrophy induced by DEHP under the present experimental conditions. In the liver, DEHP administration caused hypertrophy with changes in several metal concentrations and serum biochemical parameters. Co-administration of DEHP and AdoCbl or MeCbl did not prevent these hepatic changes, but aggravated hypolipidemia. The results demonstrated that the preventive effect of AdoCbl was a testicular specific action, and this effect may be stimulated solely by AdoCbl in vitamin B12 groups. PMID- 8198429 TI - A comparative study of the kinetics and bioavailability of pure and soil-adsorbed naphthalene in dermally exposed male rats. AB - The aim of this study was to utilize pharmacokinetic techniques to assess the bioavailability of sandy or clay soil-adsorbed naphthalene vs chemical alone following dermal treatment of male rats. Animals were exposed to 43 micrograms total of 14C-naphthalene (pure or adsorbed to one of two soils) introduced into a shallow glass cap covering a 13-cm2 area on the skin of each rat. While both soils delayed the time to reach maximum plasma concentration of radioactivity and significantly increased the half-life of plasma absorption, only sandy soil significantly decreased the peak plasma concentration of radioactivity versus the pure compound. Within 12 h after dermal application, approximately 50% of the naphthalene dose was excreted in the urine of the pure and clay soil-adsorbed groups. However, when naphthalene was adsorbed to sandy soil, the percentages of the initial dose excreted in the urine collected between 0-12 h and 12-24 h were nearly equal (33-39%). Furthermore, sandy soil adsorption shifted the secondary excretion route from expired air to feces and significantly lowered the amount of radioactivity in expired air relative to naphthalene alone. In the presence of sandy soil, a significantly larger amount of radioactivity washed off of the skin application sites. In all groups the predominant urinary metabolites determined by high performance liquid chromatography were 2,7- and 1,2 dihydroxynaphthalenes. PMID- 8198430 TI - [Accumulation and stability of drugs in hair]. AB - The transfer of cocaine and methadone into and out of human hair was investigated in vitro. A transfer in either the one or the other direction could not be observed. In addition the drug concentrations in hair obtained form addicts at different distance from the scalp were determined. The results demonstrated a decrease of the drug levels from the proximal to the distal parts of the hair. The dimensions of the decrease varied within wide ranges. PMID- 8198431 TI - [Suicidal gunshot wounds--site and characteristics]. AB - 117 gunshot suicides (111 male and 6 females) were investigated. The head was the most favorite site of the entrance wounds and some extraordinary cases were observed. 7 cases showed more than one gunshot wounds and in two of these suicides the second shot was placed directly in the first wound. Unusual sites of the gunshot wounds were the dorsal part of the neck, the right nostril and the right ear. In one case a gun powder muzzle-loader was loaded with two projectiles and in another suicide the lethal brain damage was caused by the gas pressure due to shot from a blank gun tightly pressed to the right temporal head. PMID- 8198432 TI - [Dismemberment with unusual preservation of cadaver parts]. AB - Report on a case of criminal dismembering of a corpse and the effect of vinyl on postmortem changes. Two years after murder a dismembered body, the body parts wrapped into plastic bags, were found buried 30-50 cm deep into loose earth. The whole body as well as the inner organs were very well preserved. Obviously the air-proof conditions in the plastic bag were a supporting factor for the good preservation. PMID- 8198433 TI - [Medical autopsy. Problems in the medical field, in judicial inquiries and with federal laws]. AB - A basic duty of coroner's inquest is to ascertain whether death was due to an internal or external cause or cause of death remains unclear; economic constrains and less effort for the coroner's inquest lead to blunders on several levels: the physician's level, the level of judicial inquiry and the Land governments. Typical negative and positive marks as well as intermediate stages on each of these levels are pointed out, perspectives are shown. PMID- 8198434 TI - [Confusing muscular hemorrhage in a drowned cadaver. A contribution to differentiation between vital and postmortem changes]. AB - The autopsy on an body recovered from the water showed evidence of drowning and, in addition, the occurrence of extensive intramuscular bleeding on the neck, in the area of the shoulder girdle and the upper arms. There was a suspicion that criminal violence had been used, and the police carried out extensive investigations; these were inconclusive. The subsequent histological examination of the affected musculature revealed "reactive" changes throughout which corresponded to post mortem damage. The case presented here serves to illustrate the usefulness of muscle histology for differentiating between the occurrence of intramuscular bleeding before and after death; the corresponding histological criteria are outlined. PMID- 8198435 TI - Antipoliovirus activity of isothiazole derivatives: mode of action of 5,5' diphenyl-3,3'-diisothiazole disulfide (DID). AB - In this report we describe the antiviral activity of 5,5'-diphenyl-3,3' diisothiazole disulfide (DID) and discuss its mode of action. DID selectively inhibits the replication of poliovirus type 1 (therapeutic index = 255) by affecting some early process of the virus growth cycle. The compound does not interfere with adsorption and internalization of virus to HEp-2 cells, nor with uncoating of the viral RNA. However, no viral RNA synthesis occurs after 2 h post infection in the presence of 50 microM DID. Thus, we investigated some molecular events in poliovirus replication occurring between uncoating and viral RNA synthesis. In our experimental design, we studied the activity of RNA polymerase complex isolated from HEp-2 infected cells in the presence or absence of DID. Our results showed that the RNA polymerase complex was formed in the presence of DID. On the contrary, DID markedly inhibited poliovirus RNA synthesis in a cell-free system using RNA polymerase complex isolated from infected cells. These findings indicate that DID may exert its antiviral activity by preventing viral RNA chain elongation via the inhibition of replicase activity and/or interfering with viral RNA polymerase complex. PMID- 8198436 TI - Influenza virus subtypes in aquatic birds of eastern Germany. AB - We report the findings of a 12-year surveillance study (1977-89) of avian influenza A viruses in eastern Germany. Viruses were isolated directly from feral ducks (n = 236) and other wild birds (n = 89); from domestic ducks (n = 735) living on a single farm; and from white Pekin ducks (n = 193) used as sentinels for populations of wild aquatic birds; mainly sea birds. The efficiency of virus isolation was 9.9% overall, with considerable variability noted among species: 8.7% in wild ducks, 0.9% in other feral birds and 38% in Pekin ducks. Use of sentinel ducks in wild pelagic bird colonies improved virus detection rates fivefold, suggesting that this approach is advantageous in ecological studies. Among the 40 different combinations of hemagglutinin (HA) and neuraminidase (NA) subtypes we identified, H6N1 predominated (23.6% for all avian species), followed by H4N6 (11%). Among individual species, the frequency profiles favored H2N3 (20.8%) and H4N6 (20.3%) in feral ducks; H7N7 (22.3%), H4N6 (24.4%) and H2N3 (10.4%) in Pekin ducks used as sentinels; and H6N1 (34.8%) and H6N6 (15.1%) in domestic ducks maintained on a single farm. By relying on sentinel birds for serological assays, it was possible to trace an "influenza season" in feral swan populations, beginning in August and continuing through the winter months. Comparison of subtype distribution of influenza viruses for Europe and North America showed significant differences. This supports the fact of two geographically distinct gene pools of influenza viruses in birds connected with their distinct flyways of each hemisphere. The high frequency of isolation of H2 influenza viruses is of considerable interest to those interested in the recycling of this subtype in humans. Similarly the frequent isolation of H7N7 influenza viruses raises concern about reservoirs of potentially pathogenic influenza virus for domestic poultry. Our results confirm the existence of a vast reservoir of influenza A viruses in European aquatic birds, which possesses sufficient diversity to account for strains that infect lower animals and humans. PMID- 8198437 TI - An infectious cDNA copy of the genome of a non-cardiovirulent coxsackievirus B3 strain: its complete sequence analysis and comparison to the genomes of cardiovirulent coxsackieviruses. AB - The genome of the non-cardiovirulent coxsackievirus B3 (CVB3) strain CVB3/0 was cloned and sequenced to aid in the elucidation of the viral genetic basis for the CVB3 cardiovirulent phenotype. Reverse-transcribed sub-genomic complementary DNA (cDNA) fragments were enzymatically amplified using generic oligonucleotide primers and were assembled as a complete infectious genomic copy (pCVB3-0) downstream of the T7 RNA polymerase promoter. Positive-strand viral RNA transcribed from pCVB3-0 using T7 RNA polymerase and transfected into HeLa cells produced infectious virus (CVB3/0c). No differences in phenotype were observed comparing growth of CVB3/0c to the parental CVB3/0 in HeLa single-step growth curves, virus yields, or plaque size. When inoculated into C3H/HeJ mice, CVB3/0c achieved cardiac titers equivalent to the parental CVB3/0 and like the parental virus, demonstrated a non-cardiovirulent phenotype. The nucleotide sequence of the cloned CVB3/0 genome was determined and compared to the genomes of infectious cDNA clones of cardiovirulent CVB3 strains. Two consistent differences among nucleotides in non-translated regions and 8 amino acid differences relative to two well-characterized infectious cDNA copies of genomes from cardiovirulent CVB3 strains were identified. PMID- 8198438 TI - Comparison of three different recombinant hepatitis B virus core particles expressed in Escherichia coli. AB - The properties of three different recombinant hepatitis B virus core proteins expressed in Escherichia coli were compared: an N-terminal fusion protein, a C terminally truncated protein and a sequence-authentic protein. All three proteins assembled into capsid-like particles with typical HBc-antigenicity, sedimentation behavior and distinctive electron microscopical images. Apart from this, however, variant HBc proteins displayed properties different from sequence-authentic HBc protein p21.4. Unlike p21.4, the particles of the N-terminal fusion protein p22.2 were sensitive to proteolytic attack by trypsin at variable sites within its arginine-rich C-terminus but not in its extended N-terminus. We therefore conclude that the C-terminal region is located on the surface of the p22.2 particle. These particles also showed increased HBe-antigenicity, as did the C terminally truncated core particles p17.6, and to an even greater extent p18* particles which were derived from p22.2 by tryptic digestion. This might be interpreted as evidence for an--albeit minor--structural change. All variant core particles were less stable and contained less RNA. Electron microscopic indication for DNA binding of C-terminal deleted p17.6 particles was obtained using an aqueous spreading technique. PMID- 8198439 TI - Artificial defective interfering RNAs derived from RNA 2 of beet necrotic yellow vein virus. AB - Long internal deletions were introduced into cloned cDNA of beet necrotic yellow vein virus RNAs 1-4 and transcripts containing the deletions were tested for their ability to inhibit replication of viral RNA in Chenopodium quinoa protoplasts and plants. No inhibition was observed with the deletion mutants based on RNAs 1, 3 and 4 but the RNA 2 deletion mutants all provoked a dramatic inhibition of synthesis of viral RNAs 1 and 2. PMID- 8198440 TI - Induction of apoptosis in a T lymphoblastoid cell line infected with feline immunodeficiency virus. AB - The mechanism of cell death induced by feline immunodeficiency virus (FIV) infection was investigated in an interleukin 2(IL-2)-dependent T-lymphoblastoid cell line (MYA-1). DNA extracted from FIV-infected MYA-1 cells showed a ladder of nucleosomal DNA, indicating that the cytopathic effect (CPE) observed in these cells was due to apoptosis. Infection of MYA-1 cells with FIV was associated with suppression of the proliferative response of the cells to exogenous IL-2 prior to DNA fragmentation. These findings suggest that FIV-induced CPE in these T lymphoblastoid cells is associated with apoptosis possibly due to a defect in the IL-2 signal transduction pathway. PMID- 8198441 TI - A field isolate of Sendai virus: its high virulence to mice and genetic divergence form prototype strains. AB - A field isolate of Sendai virus, the Hamamatsu strain, was far more virulent in mice than the prototype Z strain. The Hamamatsu strain replicated more efficiently in the mouse lung than the Z strain, causing deteriorating lung lesions. Nucleotide sequence analysis of the HN, F and M genes revealed that the Hamamatsu strain was divergent from the prototype Z, Harris and Fushimi strains. PMID- 8198442 TI - High similarity among the tomato yellow leaf curl virus isolates from the west Mediterranean basin: the nucleotide sequence of an infectious clone from Spain. AB - An isolate of tomato yellow leaf curl geminivirus, from the first epidemic outbreaks that occurred in Murcia, Spain (TYLCV-M) in 1992, was cloned and its nucleotide sequence was determined. The circular single stranded DNA consisted of 2777 nucleotides. The genome organization resembled that of other TYLCV sequenced so far; regulatory signal sequences for bidirectional transcription and for polyadenylation of the transcripts were localized in the sequence. Infectivity of the cloned DNA was demonstrated by subcloning a 1.8 mer of TYLCV-M in pBin19 and agroinoculating it into tomato and Nicotiana benthamiana plants. Symptoms and viral DNA forms in agroinfected plants did not differ from those of field infected ones. Sequence comparisons with other TYLCV isolates show a high homogeneity between isolates from the West Mediterranean Basin, suggesting the presence of a geographical cluster. PMID- 8198443 TI - Cosmid cloning and restriction endonuclease mapping of the herpesvirus of turkeys (HVT) genome. AB - The genomic libraries of the herpesvirus of turkeys (HVT) presented to date do not include the entire genome. To construct a complete genomic library, HVT DNA was partially digested with Sau3A and inserted into the double cos site vector pcos2EMBL. The PstI maps derived from the partial Sau3A library demonstrate that the left region of the genome compared to the right area is overrepresented. Similar to the libraries of the HVT genome established earlier, a defined portion of the middle genomic region, however, is not contained in the partial Sau3A library. Cloning of HVT DNA in pcos2EMBL, employing BamHI for the partial digestion step, enabled to find the recombinant cosmid cBL267 which carries the BamHI-C and -D fragment as DNA insertion. As shown by Southern blot hybridization, the BamHI-C fragment ranges in a size to close the gap in the partial Sau3A library and thus guarantees the completeness of the genomic library of HVT which consists of seven overlapping cosmid clones (cBL1, cBL328, cBL11, cBL267, cBL27, cBL33, and cBL34). PMID- 8198444 TI - Identification of four genes involved in the lysogenic pathway of the Salmonella newington bacterial virus epsilon 34. AB - A structure/function study has been initiated for the epsilon 34 bacteriophage proteins involved in lysogeny in Salmonella newington. Hydroxylamine and nitrosoguanidine mutagenesis of a wild type epsilon 34 phage was used to generate clear plaque variants. Complementation analysis was used to define four genes involved in the phage lysogenic pathway. A relative mapping order has been established. In addition, a virulent mutant, epsilon 34vir82, which defines a repressor binding site has been isolated. PMID- 8198445 TI - 3'-terminal sequence of a small round structured virus (SRSV) in Japan. AB - We determined the nucleotide sequence of about 1,000 bases from the 3'-terminus of a small round structured virus (SRSV), which caused a gastroenteritis outbreak in Chiba Prefecture, Japan, in 1987. The sequence was compared with the corresponding sequence region of Norwalk virus; it consisted of a part of the open reading frame 2 (ORF2), whole ORF3, and 3'-noncoding region (NCR). The 624 base-long ORF3 had sequence homology of 68% with the corresponding region of Norwalk virus. (The amino acid sequence homology was 74%.) The 94-base-long NCR had 65% homology with Norwalk virus. We then selected two consensus-sequence portions in the above sequence between Chiba and Norwalk viruses for primers in the reverse transcriptase-polymerase chain reaction (RT-PCR). Using this primer set, we detected 669-bp bands in agarose gel electrophoresis of RT-PCR products from feces containing Chiba or Norwalk viruses. Furthermore, in Southern hybridization with Chiba probes which were labeled with digoxigenin-dUTP in PCR, the bands of the two viruses were clearly stained under a low stringency condition. Since both Chiba and Norwalk viruses were detected by the above primer set although they are geographically and chronologically different viruses, our primer-pair may be useful for detection of a broad range of SRSVs which cause gastroenteritis in different areas. PMID- 8198446 TI - Expression of env gene of bovine leukemia virus in rodent cells. AB - The BamHI-BamHI fragment of the env gene of bovine leukemia virus (BLV) cloned in pMMEx expression vector was transfected into Chinese hamster cells. Monoclonal antibodies (MAbs) directed against both conformational and sequential epitopes of gp51 of BLV recognized viral polypeptides expressed in hamster cells in Western blotting and enzyme-linked immunosorbent assay. PMID- 8198447 TI - Revision of the taxonomy of the Coronavirus, Torovirus and Arterivirus genera. PMID- 8198448 TI - Female characteristics in the Drosophila melanogaster-sigma virus system in natural populations from Languedoc (southern France). AB - The Drosophila melanogaster-sigma virus system has been extensively analysed for some years in Languedoc. The sigma virus, endemically present in natural populations of the fly, is not contagious but vertically transmitted. The frequency of infected flies dramatically increased from 1983 to 1988 in Languedoc and the increase was clearly correlated with some viral characteristics. From 1988 onwards, this frequency steadily decreased. Three zones were identified in Languedoc, from North to South, in each of which the virus evolved differently. Transovarial transmission and other parameters on the female side in the host virus system were investigated in samples collected in 1992. There were differences in values between the three zones. The contribution of these parameters to the observed differential frequencies of infected flies is discussed. PMID- 8198449 TI - Inhibition of type 5 adenovirus infectivity by periodate oxidation. AB - Periodate oxidation of purified type 5 Adenovirus (Ad5) led to a mean loss of infectivity of 6.84 logs. There were no significant differences in adsorption and penetration between oxidized and mock-oxidized virus. However, after infection with oxidized virus, no synthesis of viral structural proteins could be detected and a 78.5% inhibition of viral DNA synthesis was observed. Labelling experiments performed by treating oxidized and mock-oxidized virus with tritiated sodium borohydride revealed that the fiber glycoprotein was one of the proteins labelled in oxidized virus whereas no labelled proteins were detected in non oxidized virus. In addition, it was found that one mol of formaldehyde generated during oxidation of sugar residues was bound per 500 base pairs in oxidized virus. One consequence of this in situ generation of formaldehyde is the formation of DNA protein crosslinks. The DNA so crosslinked showed different patterns of restriction fragments with endonucleases such as Hpa I, Hind III and Kpn I but not with Xho I. PMID- 8198450 TI - Inactivation of human cytomegalovirus by sodium periodate oxidation. AB - Human cytomegalovirus (HCMV), oxidized by sodium periodate (NaIO4), is incapable of giving rise to viral progeny in cell culture. At a NaIO4 concentration as low as 5 mM, there is a loss of at least 6 logs of viral infectivity which occurs very rapidly (less than 5 min). Further, the inactivation is a first-order reaction depending on the periodate concentration. Adsorption to the cell surface, penetration into cells, and penetration of the viral DNA into cell nuclei were found to occur identically in mock oxidized and oxidized HCMV. Since the carbohydrate moiety of viral glycoproteins was the target of periodate attack, these observations strongly suggest that the structural integrity of the sugar residues is not a prerequisite for adsorption and penetration. Nevertheless, no evidence for viral DNA or protein synthesis was detected in cells infected with oxidized virus, and even after 3 weeks in culture, no cytopathic effect was observed. PMID- 8198452 TI - [Molecular biology of mite antigens]. PMID- 8198451 TI - Double fluorescence analysis of human cytomegalovirus (HCMV) infected human fibroblast cultures by flow cytometry: increase of class I MHC expression on uninfected cells and decrease on infected cells. AB - Cultured human foreskin fibroblasts (HFF) were infected with different multiplicities of infection (moi 0.001-0.1) of human cytomegalovirus (HCMV) strain AD 169 or a clinical isolate. Percentage of infected cells was determined by analysis of immediate early (IEA), early (EA), and late (LA) virus antigen expression with flow cytometry or by immunoperoxidase staining. Changes in the expression of class I MHC surface molecules were demonstrated by comparing the mean fluorescence intensities of infected HFF cultures with those of mock infected cell cultures by flow cytometry. At day three post infection single fluorescence analysis showed that infected HFF cultures split into low and high density class I MHC bearing cells. The addition of anti-interferon beta reduced the expression of class I MHC, distinctly. The assumption that infected cells down-regulate and uninfected cells up-regulate their expression of class I MHC molecules was demonstrated by double fluorescence analysis both with flow cytometry and fluorescence microscopy. Analysis of class I MHC-antigen expression versus immediate (IEA, mab E13), early (EA, mab 9221), or late (LA, mab BM219) virus antigen expression yielded three cell populations of HCMV infected HFF cultures three days post infection: 1. uninfected cells with an increase of class I MHC, 2. high density class I MHC, IEA and/or EA expressing cells, and 3. low class I MHC, IEA, EA and LA expressing cells. PMID- 8198454 TI - [Study of endothelin: distribution in the airway and release from nasal epithelial cells]. AB - In order to clarify the existence and the role of endothelin in the respiratory tract, we investigated the distribution of endothelin in the respiratory mucosa by immunohistochemistry. The endothelin release from cultured nasal epithelial cells of allergic mucosa and polyp mucosa was also studied by RIA. Endothelin was distributed in the epithelium, endothelium of vessels, and submucosal glands in both nasal and bronchial mucosa. Moreover, in bronchial mucosa smooth muscles of bronchus had also positive staining of endothelin. On the other hand, 1.8 x 10( 11) pg of endothelin was released to culture medium from single cultured epithelial cell of allergic nasal mucosa, and 2.8 x 10(-11) pg of endothelin was released to culture medium from that of nasal polyp. These increase of endothelin was correlated with an increase of cultured epithelial cells from both nasal allergy mucosa and nasal polyp, of which the cell number was increased depend on the concentration of FCS. These results indicate that endothelin in the respiratory mucosa acts on not only control of blood flow and air flow, but also has some reaction which was related on the mucosal epithelium such as epithelial cilially movement. Endothelin has some role in inflammation because endothelin was increased more in nasal polyp culture medium than in allergic mucosa culture medium. PMID- 8198453 TI - [Fluticasone propionate reduced the production of GM-CSF, IL-6 and IL-8 generated from cultured nasal epithelial cells]. AB - Accumulation of mast cells and eosinophils in the nasal epithelial layer occurs in nasal allergic reactions and nasal polyps. We have already demonstrated that fluticasone propionate (FP) inhibits the accumulation of mast cells and eosinophils locally, and also improves the nasal symptoms of patients with allergic rhinitis. We hypothesized that cytokines generated from nasal epithelial cells possibly contribute to the accumulation of cells and eosinophils in the nasal epithelial layer. In this experiment we examined the inhibitory effect of FP on the production of GM-CSF, IL-6 and IL-8 by culturing of nasal epithelial cells in vitro. Our results show that FP significantly reduces the level of GM CSF, IL-6 and IL-8 in the supernatant of culture media of nasal epithelial cells for a period of 6 days. In addition, preincubation of nasal epithelial cells with FP for 6 days causes a significant reduction of GM-CSF levels in the supernatant of culture-media of cultured nasal epithelial cells during the subsequent period of 6 days without FP. These results provide evidence that FP inhibits the accumulation of mast cells and eosinophils in the mucoepithelial layer of the nasal membrane. PMID- 8198455 TI - [Three cases of typical cryptomeria pollen asthma]. AB - We treated three asthmatic children diagnosed as typical cryptomeria pollen asthma (Cryptomeria japonica). Wheezing started from one to four years after onset of pollinosis. Asthmatic attacks occurred one or several days after pollen counts increased. We could find asthmatic attacks in the years when the pollen counts were higher than in average years. In the laboratory findings, only specific IgE antibody to cryptomeria with its high titer of over 17.5 PRU/ml was detected in these three cases. Allergen inhalation tests were performed with positive results in the two cases, suggesting that these three cases were typical child cryptomeria pollen asthma. PMID- 8198456 TI - [Enzyme-linked immunosorbent assay for the quantification of Cry j I and Cry j II]. AB - Enzyme-linked immunosorbent assays (ELISA) were developed to specifically quantify the two major allergens from Japanese cedar pollen, Cry j I and Cry j II. Polystyrene microplates coated with antibodies specific for Cry j I or Cry j II were incubated with an allergen and then with biotinylated anti-Cry j I or Cry j II antibody. The bound allergen-biotin Ab complexes were detected with HRPO conjugated streptavidin and an enzyme substrate. The working ranges of Cry j I ELISA and Cry j II ELISA were 0.3-20 ng/ml and 0.6-20 ng/ml, respectively. Intra- and inter-assay coefficients of variation for reproducibility were 1.5-10.3% and 0.9-12.9%. These ELISA systems showed no cross-reactivity between Cry j I and Cry j II and showed little cross-reactivity with pollen allergens of plants botanically related to the Japanese cedar. Using the Cry j I ELISA and the Cry j II ELISA, it was possible to quantify Cry j I and Cry j II easily and accurately. These ELISA systems will be useful in various fields, especially for the analysis and standardization of the allergens necessary for diagnosis and treatment of Japanese cedar pollinosis. PMID- 8198457 TI - [Spontaneous IgE production in asthmatic children]. AB - In this study, we demonstrated spontaneous IgE production by peripheral blood mononuclear cells of asthmatic children. In 26 asthmatic children, the level of spontaneous IgE ranged 0.1-15.0 IU/ml and in 5 healthy normal children showed under 0.051 IU/ml. In 5 of asthmatic children, specific antibody of Dermatophagoides farinae was detected from PBMC by CAP RAST. In healthy normal children, specific antibody of Df was not detected. Spontaneous IgE production by PBMC and serum IgE level showed well correlation (gamma = 0.835, p < 0.001). Spontaneous IgE production and specific antibody of Df by PBMC also showed well correlation (gamma = 0.717, p < 0.001) IgE production of asthmatic children was inhibited by IFN-gamma. PMID- 8198458 TI - [Analysis and regulation of interferon-gamma production by peripheral blood lymphocytes from patients with bronchial asthma]. AB - As with normal lymphocytes, small amounts of interferon-gamma (IFN-gamma) were spontaneously produced by lymphocytes from patients with bronchial asthma, and this bronchial asthma, and this production was markedly enhanced by concanavalin A (Con A) stimulation. Distinct from normal lymphocytes, however, IFN-gamma synthesis from patients' lymphocytes decreased in a dose dependent manner on stimulation with Dermatophagoides farinae (Df) antigen. IFN-gamma-producing cells are defined as being of the CD4+ 45RO+ T cell subset, which failed to produce IFN gamma in Df-stimulated patients' lymphocytes. As the decreased production of IFN gamma by antigenic stimulation was exclusively induced by Df antigen, but not by ovalbumin (OVA) or Japanese cedar (JC) antigen, it is concluded that Df antigen specifically suppressed IFN-gamma production in patients' lymphocytes. The IFN gamma synthesis from normal lymphocytes was suppressed by the addition of IL-4 in a dose dependent manner. Moreover, anti-IL-4 antibody dose dependently enhanced IFN-gamma production from Df-stimulated patients' lymphocytes but not from unstimulated lymphocytes. These results indicate that IFN-gamma production by patients' lymphocytes is suppressed by the endogenous IL-4. Reduced IFN-gamma production in patients' lymphocytes on stimulation with Df antigen may lead to the overproduction of IgE in vivo. PMID- 8198459 TI - [Prevalence rate of allergic diseases among school children in Okinawa]. AB - The prevalence rate of allergic diseases among 10137 elementary school children in Okinawa was studied by questionnaire. The results are as follows: (1) The prevalence rate of allergic diseases was 23.8%. (2) The prevalence rates of bronchial asthma and its remission were 5.0% and 2.1% respectively. (3) There was no statistically significant difference in the prevalence rates of bronchial asthma and its remission between any grade. (4) There were at least one smoker in 58.8% of family with asthmatic children. (5) There were positive family histories of bronchial asthma among 45% of family with asthmatic children. (6) The prevalence rats of allergic rhinitis, atopic dermatitis were 12.9% and 9.5% respectively. Nishima et al. have reported that the prevalence rate and its remission of bronchial asthma was 4.6% and 1.6% respectively. And they also have reported that the prevalence rate of allergic rhinitis and atopic dermatitis was 15.9% and 17.3%. Prevalence rate of allergic diseases in elementary school children in Okinawa was somewhat different from that from other study in Japan. Because about 25% of children have allergic diseases in Okinawa, it would be very important to comprehend the children with allergic diseases for adequate control and management. PMID- 8198460 TI - A case report of drug-induced allergic hepatitis probably due to the N methyltetrazolethiol group cephalosporin. AB - Drug-induced allergic hepatitis occurred in a patient being treated with cefpiramide sodium. A lymphocyte blast transformation test suggested that the N methyltetrazolethiol group of the drug was responsible for the induction of acute hepatitis. A detailed case report and discussion of the relevant literature are presented in this paper. PMID- 8198461 TI - [Activated T cells in the peripheral blood of patients with subacute myelo-optico neuropathy (SMON)]. AB - It has been reported that some kinds of immunological abnormalities are more frequently seen in patients with subacute myelo-optico-neuropathy (SMON), as compared with normal subjects. In order to examine whether ageing and clioquinol intoxication in the past may be implicated in the immunological disorders of the patients, we investigated soluble interleukin-2 receptors (sIL-2R) and an appearance of HLA-DR positive T cells using two color flow cytometry analysis in the peripheral blood of 29 patients with SMON, who lived in Nagano Prefecture. The mean level of HLA-DR positive T cells in the total of SMON patients was significantly high as compared with that of normal subjects (p < 0.001). The mean levels of HLA-DR positive T cells were also significantly high in SMON patients in their fifties and younger, sixties, and seventies and older, respectively, as compared with those of normal subjects (p < 0.05, respectively). The mean level of sIL-2R in the total of SMON patients was significantly high as compared with that of normal subjects (p < 0.01). The mean levels of sIL-2R were also high in SMON patients in their fifties and younger, sixties, and seventies and older. An especially significant increase was seen in SMON patients in their sixties (p < 0.01). SMON patients with higher levels of HLA-DR positive T cells tended to have higher levels of sIL-2R, and statistical analysis showed a significant correlation between them (r = 0.696, p < 0.001). An increase in HLA-DR positive T cells and sIL-2R indicates an increase in activated T cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198462 TI - Cerebral asymmetry, planum temporale, and aberrant neurodevelopment in schizophrenia. PMID- 8198463 TI - Trends in the practice of neurology. Responding to health system reform. PMID- 8198464 TI - Treatment of Wilson's disease with ammonium tetrathiomolybdate. I. Initial therapy in 17 neurologically affected patients. AB - OBJECTIVE: To test the efficacy and toxicity of a new drug, ammonium tetrathiomolybdate, in the initial treatment of a relatively large series of patients presenting with neurologic signs and symptoms caused by Wilson's disease. The key aspect of efficacy was to preserve the neurologic function present at the onset of therapy. DESIGN: An open study of 17 patients treated for 8 weeks each. Neurologic function was evaluated by frequent quantitative neurologic and speech examinations. Several copper-related variables were studied to evaluate the effect of the drug on copper, and a large number of biochemical and clinical variables were studied to evaluate potential toxicity. Patients were then followed up at yearly intervals, with follow-up periods of 1 to 5 years reported. SETTING: A university hospital referral setting INTERVENTION: Patients were generally treated for 8 weeks with tetrathiomolybdate, followed by zinc maintenance therapy. MAIN OUTCOME MEASURES: Neurologic function was evaluated by quantitative neurologic and speech examinations. RESULTS: None of the patients suffered a loss of neurologic function. Copper status and potential further toxic effects were generally well controlled quickly. No toxic effects resulted from administration of tetrathiomolybdate. During the ensuing period of follow-up of 1 to 5 years, neurologic recovery in most patients was good to excellent. CONCLUSIONS: Tetrathiomolybdate appears to be an excellent form of initial treatment in patients with Wilson's disease presenting with neurologic signs and symptoms. In contrast to penicillamine therapy, initial treatment with tetrathiomolybdate does not result in further, often irreversible neurologic deterioration. PMID- 8198465 TI - Ultrastructural localization of anti-Purkinje cell antibody-binding sites in paraneoplastic cerebellar degeneration. AB - OBJECTIVE: Anti-Purkinje cell antibodies have been found specifically in patients with paraneoplastic cerebellar degeneration. We investigated the ultrastructural localization of antigen-antibody reaction products by means of immune electron microscopy, using an antibody identical to anti-Yo antibody, which occurs most frequently and which immunostains the cytoplasm of Purkinje cells. DESIGN: The antibody used here (anti-Us) was obtained from a patient with paraneoplastic cerebellar degeneration. Based on results indicating 94% homology between the amino acid sequences of the antigens recognized by anti-Us and anti-Yo antibodies, these two antigens are considered to be the same. After immunostaining of the specimen from the rat cerebellum by the avidin-biotin peroxidase complex method, ultrathin sections were examined with an electron microscope without counterstaining. RESULTS: Immunoreaction products were found to be localized on membrane-bound ribosomes and free ribosomes. There were no reaction products in the endoplasmic reticulum lumen, smooth endoplasmic reticulum, Golgi complex, mitochondria, or nucleus. CONCLUSION: Although it has been noted that there is a leucine-zipper motif in the amino acid sequence of the antigenic protein that can bind to DNA, our findings indicate that this protein exists on the ribosome and may regulate protein synthesis rather than gene expression in the nucleus. PMID- 8198466 TI - Four-year follow-up of adrenal-to-brain transplants in Parkinson's disease. AB - OBJECTIVE: Evaluate long-term efficacy of autologous adrenal-to-caudate transplants in idiopathic Parkinson's disease refractory to medical treatment. DESIGN: Subjects underwent evaluations several times preoperatively on the University of California-Los Angeles Parkinson's Disease Disability Scale and the Hoehn and Yahr stage of disease. Postoperatively, they were also repeatedly rated on the Unified Parkinson's Disease Rating Scale. SETTING: Clinical visits and surgery took place at the University of California-Los Angeles Center for the Health Sciences. PATIENTS: Three men and one woman, ages 44 to 55 years, were followed up for several years preoperatively. At surgery, disease durations ranged from 7 to 16 years. Originally, all patients had a good response to levodopa, but for several years preoperatively, they had had fluctuating responses and a short duration of drug action. INTERVENTION: Right adrenalectomy was performed through a midline abdominal incision. Open craniotomy exposed the head of the right caudate into which pieces of adrenal medulla, 1 to 2 mm in size, were implanted. MAIN OUTCOME MEASURES: Scores on the three major scales (see "Design") were augmented with the number of hours "off" per day and severity of abnormal involuntary movements. Disease progression of each patient was compared with his own preoperative course and with those of a cohort of patients with Parkinson's disease followed up for 14 years who had received medical treatment without transplant surgery. RESULTS: After 4 years, transplants continued to be beneficial to three patients and had been of brief transient benefit to the fourth. The course of disease was more benign postoperatively than preoperatively and was more slowly progressive than that in the cohort. CONCLUSION: Improvement was not sufficient to justify adrenal transplants as routine therapy but does point the way to the use of other dopamine tissue transplantation. PMID- 8198467 TI - Mononeuritis multiplex and vasculitis. Association with anti-neutrophil cytoplasmic autoantibody. AB - Mononeuritis multiplex is known to occur in many illnesses including certain types of systemic vasculitis. Anti-neutrophil cytoplasmic autoantibody (ANCA) has been described in association with Wegener's granulomatosis, polyarteritis nodosa, pauci-immune necrotizing crescentic glomerulonephritis, and so-called ANCA-associated vasculitis. We describe three patients who presented with mononeuritis multiplex and positive tests for ANCA. A careful search revealed underlying vasculitis in two of the three patients. Whereas both respiratory and renal involvement are well known in ANCA-associated vasculitis, to our knowledge the relationship of mononeuritis multiplex and ANCA positivity has not previously been described. The three patients were treated with steroids and oral cyclophosphamide. All demonstrated marked clinical improvement, as well as a decrease or disappearance of the ANCA. Since mononeuritis multiplex may be a presenting symptom of many illnesses, a serological marker may be helpful for early diagnosis and prompt treatment. PMID- 8198468 TI - Comparison of neurologic changes in 'successfully aging' persons vs the total aging population. AB - OBJECTIVE: To determine age-related changes in neurologic function in the general population. DESIGN: To administer a neurologic examination to participants in such a way that it is possible to calculate the proportion of elderly persons in the population with each abnormal finding and the proportion of persons with each finding but without evidence of the medical and neurologic diseases likely to produce neurologic abnormalities (eg, stroke and diabetes). SETTING: Individuals were selected from a community-dwelling population. PARTICIPANTS: A stratified random sample of 467 persons aged 65 years and older were evaluated. RESULTS: Many neurologic abnormalities are increasingly common with advancing age and are present in a substantial portion of the elderly population. The prevalence of abnormal neurologic findings not attributable to disease, however, is substantially lower, typically one half to one third the total prevalence. Moreover, the increase with age in the prevalence of abnormal neurologic findings not attributable to major disease varies substantially among the different measures. CONCLUSIONS: Primitive reflexes and measures of gait show statistically significant increases with age in multiple measurement domains, suggesting a selective age-related vulnerability. PMID- 8198469 TI - Activity of S-adenosylmethionine decarboxylase, a key regulatory enzyme in polyamine biosynthesis, is increased in epileptogenic human cortex. AB - OBJECTIVE: We measured the activity of S-adenosylmethionine decarboxylase, a key regulatory enzyme of polyamine biosynthesis, in the temporal cortex of patients with epilepsy. DESIGN: Cortical surgical specimens were obtained following anterior temporal lobe resection for intractable epilepsy. Enzyme activity was compared in nonepileptogenic (n = 16) and epileptogenic (spontaneously discharging; n = 19) regions. RESULTS: Mean enzyme activity was increased by 44% in samples from epileptogenic cortex compared with samples from nonepileptic regions. The S-adenosylmethionine decarboxylase activity in regions of focal epileptogenic discharges was also increased in five patients compared with paired samples from the nonepileptogenic portion of the same gyrus (+55%). CONCLUSIONS: Elevated activity of S-adenosylmethionine decarboxylase in regions of active epileptogenic cortical discharges suggests that a disturbance of the polyamine system may be involved in the maintenance of hypersynchronous discharges, perhaps through a modulatory action at the excitatory N-methyl-D-aspartate-preferring glutamate receptor. PMID- 8198470 TI - The natural history of Alzheimer's disease. Description of study cohort and accuracy of diagnosis. AB - OBJECTIVE: We describe the sampling, initial evaluation, and final diagnostic classification of subjects enrolled in a natural history study of Alzheimer's disease (AD). DESIGN: Volunteer cohort study. SETTING: Multidisciplinary behavioral neurology research clinic. PATIENTS OR OTHER PARTICIPANTS: Three hundred nineteen individuals were enrolled in the Alzheimer Research Program between March 1983 and March 1988. Of these, 204 were originally classified with AD, 102 were normal elderly control subjects, and 13 were considered special cases. MAIN OUTCOME MEASURES: Final consensus clinical diagnosis, final neuropathologic diagnosis, and death. RESULTS: Of the 204 patients enrolled in the study, re-review after as many as 5 years of follow-up resulted in a final clinical classification of 188 with probable AD. Seven patients were believed to have a significant vascular component to the dementia, three were found to have developed depression, and six were excluded on other clinical grounds. Neuropathologic examination of 50 brains indicated definite AD in 43. After removing these seven misdiagnosed patients, the final group of probable/definite AD totaled 181 individuals. Accuracy of the baseline clinical diagnosis relative to neuropathology was 86%, and when follow-up clinical data were considered, 91.4%. Detailed neuropsychological testing yielded high sensitivity (0.988) and specificity (0.983) to dementia. Analyses of survival time from study entry until death revealed that older patients were significantly more likely to die during follow-up, but neither sex, years of education, nor pattern of cognitive impairment were related to survival. CONCLUSIONS: These data provide the descriptive basis for future studies of this cohort. They indicate that longitudinal follow-up of demented cases increases accuracy of diagnosis, and that detailed cognitive testing aids in early classification. PMID- 8198472 TI - The neurological complications of spermatorrhoea. AB - The age-old belief that loss of sperm could be dangerous to health became a major medical concern throughout the Western world following Claude-Francois Lallemand's inflammatory warnings about the dangers of spermatorrhoea. This article investigates the leading role played by American neurologic authorities of the mid and late 1800s in their fight against the cerebral and spinal complications of spermic depletion. PMID- 8198471 TI - Risk of hypotension during apnea testing. AB - OBJECTIVE: To determine the safety of apnea testing. DESIGN: Prospective, consecutive study. SETTING: Inner-city trauma center. PATIENTS: A total of 70 apnea tests were performed on 61 comatose patients as part of the determination of brain death. RESULTS: Only 43 examinations (61%) were well tolerated. During 27 examinations (39%) patients either developed marked hypotension (> or = 15% drop in mean arterial pressure) (n = 23) or required prophylactic vasopressor manipulation (n = 4). Of the 27 examinations in which hypotension developed, 14 were aborted, two were tolerated despite marked hypotension, four were tolerated after administration of prophylactic epinephrine (n = 1) or dopamine hydrochloride (n = 3), and seven were successfully completed after increases in the rate of dopamine infusion during the test. CONCLUSIONS: Hypotension can pose a significant risk to patients undergoing apnea testing. Constant monitoring of vital signs throughout the test is essential to its safe completion. PMID- 8198473 TI - Mononeuritis multiplex. A harbinger of acute leukemia in relapse. AB - OBJECTIVE: To report the findings in a patient who developed severe mononeuritis multiplex in the setting of hematologic remission from acute myeloid leukemia. DESIGN: Single case report of the patient, hospital course, and autopsy findings. PATIENT: A 63-year-old woman with a history of acute myeloid leukemia in hematologic remission experienced a succession of acute clinical neuropathies (left median, right radial, and left sciatica) several months before hematologic relapse of leukemia. Electrophysiologic tests localized the abnormalities of the left median and right radial nerves to the arms, and a magnetic resonance imaging scan of the right arm revealed focal swelling of the radial nerve proximal to the elbow. The patient refused treatment for leukemic relapse and died about 6 months after the onset of the neuropathies. An autopsy revealed leukemic infiltrates in multiple nerves without appreciable involvement of the cauda equina or many of the proximal nerves. CONCLUSION: Mononeuritis multiplex, without polyradiculopathy or diffuse peripheral neuropathy, can be a presenting feature of leukemia. PMID- 8198474 TI - Australian country practice. PMID- 8198475 TI - The power of counselling--for better or worse? AB - Counselling is an extremely powerful tool, a vital skill to acquire in general practice today. Nevertheless, it must be used wisely and not prescribed wholesale. This article discusses counselling in general practice in relation to a series of cases where a presentation of nightmares disguised underlying repressed traumas. PMID- 8198476 TI - Pitfalls in antibiotic prescribing and how to avoid them. AB - Errors in antibiotic prescribing occur due to either a failure to understand basic antibiotic prescribing principles or through incorrect management decisions. The most common example of the former is prescribing antibiotics when they are not needed and the most common management error is failing to investigate prior to treatment. Other common management errors are outlined in the article. Avoidance of these pitfalls in antibiotic prescribing will improve patient care and reduce the likelihood of selecting for resistant strains in common pathogens. PMID- 8198477 TI - Oral ulceration. Things are not always what they seem. AB - Oral ulceration is a common complaint and is usually inconsequential. Nevertheless, when it appears for the first time in adult life, it may represent the manifestation of systemic disease. A full history and examination should be carried out and a full blood examination and ESR done. Any ulcer persisting for more than three weeks without responding to treatment should be biopsied. PMID- 8198478 TI - Symptoms and signs of retinal disease. AB - Of all the diseases of the eye, the retinal disorders are perhaps the most frequently misdiagnosed by the general medical community. The content of this article is restricted to retinal diseases and the importance of symptoms and signs in their accurate diagnosis. PMID- 8198479 TI - Reported diabetes mellitus management among South Australian general practitioners. AB - Diabetes mellitus is a chronic disease commonly managed in general practice. This article reviews the findings of a questionnaire survey of 173 randomly chosen South Australian general practitioners and their reported management in the areas of detection, diagnosis, assessment, monitoring and GP knowledge. Substantial differences between respondents were found in all areas, suggesting the need for improved educational methods aimed at all general practitioners. PMID- 8198480 TI - A brave new world in managing depression--or is it? AB - In recent years new pharmacological agents have become available for the treatment of depression encouraging many to opt for the biochemical theory as the cause of depression. This article looks at the pros and cons and whether there is still a place for non pharmacological interventions in the treatment of depression. PMID- 8198481 TI - The needs of the elderly. A short review. AB - The ageing process eventually affects us all with varying degrees of physical or intellectual deficit or both. A deeper understanding of the problems involved caused by this progressive physiological decline is necessary through education, assessment and application. Programs of rehabilitation for the elderly should attract a higher priority as much undiscovered morbidity remains. These require accurate needs targeting and implementation. Undergraduate participation in rehabilitation programs should figure much more prominently, particularly as the majority of medical students will eventually become general practitioners. PMID- 8198482 TI - Exercise and the older person. AB - The enormous pleasure that older people derive from an exercise class to music or from an aquarobics group makes instant converts of any professionals involved in these health promotion activities. Irrefutable evidence now exists to show that regular physical activity slows the rate of decline of most of the physiological parameters that we associate with health and fitness--muscle strength, aerobic capacity, reaction time and joint flexibility. Master athletes at age 60 can perform considerably better than some sedentary men at age 30. The ideal is clearly to maintain a regular regimen of physical activity throughout adult life. It has now been shown that such exercise does not need to be heavy to maintain cardiovascular and musculoskeletal fitness. Walking and swimming are as good and much safer than jogging provided the regimen entails at least 30 minutes three to four times a week. The evidence is equally strong that sedentary older people can benefit from taking up an exercise program in later life. Significant gains in muscle strength and aerobic capacity can result from gentle exercise programs carried out at least three times a week. Improvements in balance, bone density and psychological health have yet to be confirmed. Exercise and fitness programs for older adults can attract large numbers and achieve high compliance rates if the programs are accessible, affordable and, above all, fun. Men tend to be more interested in monitoring fitness levels while women are satisfied to enjoy themselves and feel better. Older adults can also continue or take up competitive sports provided simple precautions are taken to ensure cardiovascular health and to minimise injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198483 TI - "What's in a name? ...". PMID- 8198484 TI - Transvaginal ultrasound in obstetrics and gynaecology. PMID- 8198485 TI - Panic disorders and the listing of alprazolam on authority on the PBS. Beware of overdiagnosis. AB - The RACGP guidelines on benzodiazepine use (Table 2) were endorsed in March 1993, and drew on the experience of hundreds of general practitioners. Following them should ensure that there is a rational response to the new listing. PMID- 8198486 TI - The interview and the social problems. PMID- 8198487 TI - Family-based grief counselling. AB - The family constitutes the key social group involved with mourning. A model of family response patterns to bereavement is presented that contrasts the adaptive family's response with maladaptive patterns that are avoidant, distorted, inflexible or that amplify grief. Guidelines in working with these families are discussed. PMID- 8198488 TI - General practice screening for prostate cancer. A prospective study. AB - With an ageing male population it is likely that Australia will see a substantial increase in the incidence of cancer of the prostate over the next few decades. Early detection is critical if curative treatment is to be achieved but, as yet, there is no widely agreed protocol on prostate cancer screening. This study examines a particular approach in general practice and discusses its acceptance at a primary care level. PMID- 8198489 TI - Cholesterol levels in general practice. AB - In a GP setting of 2679 patients aged over 20 years, at least one cholesterol reading was known for 529 (20%). Of 1087 lipid estimations in 10 years the average cholesterol was 6.33 (SD 1.45). All 523 were given appropriate dietary advice and 40 (18%) were also given pharmacological agent(s) as well. Of 211 patients who had more than one reading done, an overall reduction of 6.4% in cholesterol was achieved and maintained for a sustained period of 3.2 years on average. PMID- 8198490 TI - Beware the demented patient. PMID- 8198491 TI - The management of hypertension in general practice. Results from the Australian Morbidity and Treatment Survey, 1990-1991. AB - Hypertension is the most frequently managed problem in general practice in Australia. This paper provides an overview of its management in general practice and draws some comparisons with an earlier study. PMID- 8198492 TI - An observational study of the NSW parent-held record in a GP setting. AB - Despite recent studies having found that doctors report high use of the parent held record (PHR), there are no studies in the literature that investigated the actual use, as opposed to reported use, of the PHR by doctors in a general practice setting. This study aimed to clarify some aspects of the actual use of the PHR by doctors in the authors' general practice setting, and by other doctors seen by the clients. The findings were encouraging in showing an increased use of the PHR linked to increased awareness. But the study also showed there is much room for improvement in educating general practitioners and other health workers about the potential benefits of the PHR. PMID- 8198493 TI - Anal fissure. PMID- 8198494 TI - Malaria prevention. PMID- 8198495 TI - What do patients expect in a general practice consultation? AB - The technique used in this study indicated that in the study group there was a high degree of concurrence between a patient's expectations and the consultation outcome. The rate of concurrence would have been much higher if the group who were 'unsure' as to their expectations had not been included. This method could be used as an instrument for continuing education by focusing a doctor's attention on patient expectations. For the doctors involved in this study it was reassuring to see that by the measure utilised they were often aware of their patients' expectations and able to direct the consultation according to this knowledge. PMID- 8198496 TI - So you want to do rural practice? PMID- 8198497 TI - A fascinating mix. PMID- 8198498 TI - Review of the opiate dependence rehabilitation program in a rural community. AB - There is little doubt that the program fills a need in the health care system of this small community. We have met with some public resistance to the provision of services for drug 'addicts', sometimes from surprising quarters. There has also been significant resistance from some potential patients. Overall we believe that the successes achieved, although few, are worthwhile and may form a useful model for programs in other small rural communities. PMID- 8198499 TI - Patient education. Glaucoma. PMID- 8198500 TI - Raising the possibility of sexual abuse. PMID- 8198501 TI - Maintaining skills in general practice. PMID- 8198502 TI - Procedural medicine in country hospitals. PMID- 8198503 TI - A mathematical study of turbulent blood flow through an arterial bifurcation. AB - A turbulent model of flow through an arterial bifurcation is proposed in order to investigate flow separation, secondary flow and the variation of pressure and stress along the wall when blood passes through a bifurcation. Blood is assumed to behave like a Newtonian fluid, with viscosity depending on the angle of bifurcation. The geometry of the models used here for aortic bifurcations is set by employing the principle of conservation of mass. The results show that: the peak axial velocity in the entrance region of the daughter vessel occurs on the inner wall of the bifurcation; a strong secondary flow may develop in the branch, which has much less effect on axial flow when the Reynolds number is low; there is a tendency toward separation in the branch with low mean flow, and the flow is increasingly disturbed as the bluntness of the apex increases. PMID- 8198504 TI - Surface doses from combined electron/photon fields in a radiotherapy. AB - Using mixed modality treatments of photon and electron beams, some skin sparing can be acquired whilst administering a safer dose to crucial structures such as the spine or lung. The combination of 6MV X-rays and 12MeV electron beams in the treatment of breast nodes is a clinical example where such treatments are beneficial. By weighting the photon and electron beams accordingly, the surface dose and dose at depth can be changed whilst not dramatically varying the depth at which the 90% dose level is maintained. In order to accurately predict near surface dose, build up results were obtained using TLD extrapolation, Markus parallel plate and Attix parallel plate ionisation chambers in a solid water phantom. This data was then used to predict surface dose due to different beam weights. Depending on the weightings given to the photon and electron beams, the surface dose and dose at depth varies. For example, when 6MV X-rays and 12MeV electrons are combined the percentage dose at surface and 20cm depth is 46%/23%, 54%/20%, 61%/15% for 60/40, 50/50 and 40/60 X-ray/electron weightings respectively. For these weightings, the depth of the 90% level remained at 30mm. From a clinical point of view this data is important, showing that the 90% level of radiation does not vary in depth significantly provided the ratio of photon/electron weights is kept within a range of 60/40 to 40/60. However by varying the weightings, the ability to control dose to skin in particular to produce the optimum level for both areas whilst still delivering the required tumour dose is obtained. PMID- 8198505 TI - Mobile telephones interfere with medical electrical equipment. AB - Electromagnetic interference in medical electrical equipment has not been a serious problem in recent years even with the proliferation of analogue mobile phones and two-way handheld radios. With the introduction of GSM digital mobile phones into Australia we have conducted measurements and found that, within 2m, the electric fields from digital mobile phones can exceed the immunity level of 7 V/m recommended by the US Food and Drug Administration (FDA) for medical electrical equipment. Current analogue mobile phones were shown to produce electric fields that exceed the 7 V/m level only at relatively shorter distances. In another test, both analogue and digital mobile phones were operated close to a range of typical medical electrical equipment. It was found that existing equipment generally meets the FDA standard, but digital mobile phones caused a variety of artefacts and alarm conditions. This problem must be addressed by the medical engineering profession; in the meantime, nursing and other staff should be educated to recognise these problems and restrictions must be placed upon the use of mobile phones in hospitals. PMID- 8198506 TI - Binding of 5,5-diphenylhydantoin with erythrocyte membrane: local lateral order parameter and strong interaction with phospholipid head groups. AB - We have studied the interaction of 5,5-diphenylhydantoin (5,5-dph), an anticonvulsant drug, with erythrocyte membrane lipids and proteins using IR spectroscopic technique. The local lateral order parameter, which is directly related to the lipid packing density, has been found to be elevated due to 5,5 dph binding. This increase has been accounted for on the basis of relaxation of local discontinuity in orientational order (defects). The transition towards an ordered structure is further supported by our experimental results which exhibit a decrease in the hydrocarbon chain mobility. The reorganization of the polar head groups due to 5,5-dph-lipid interaction leads to the absence of the bands at 1150 cm-1 (C-O stretch or C-O-C antisymmetric stretch) and 1085 cm-1 (C-O-P stretch or PO2- symmetric stretch). These bands are associated with the phospholipid head groups in erythrocyte membrane. Significant intensity changes in amide I (1650 cm-1) and amide II (1520 cm-1) have been explained using the concept of transition dipole moment coupling between C-N and N-H vibrational modes of amide II. PMID- 8198507 TI - Calibration of a cadmium IVNAA system. AB - An in vivo neutron activation analysis (IVNAA) system for the measurement of cadmium in the human liver and kidney was calibrated using cadmium doped liver and kidney phantoms in a water tank. The effect on the number of cadmium gammas detected with changes in organ position and cross-organ interference was assessed. The lower limits of detection were found to be 12 mg cadmium in the kidney and 7 ppm cadmium in the liver. This system was compared to five others using a performance index which considers equipment specifications and dose to the subject, and was found to rank second best for the liver measurements and second worst for the kidney measurements. The results from the organ position studies showed that the depth of the organs in the body has a great effect on the results, and differences between systems could be partially due to differences in calibration geometry. PMID- 8198508 TI - Wedge factors for rectangular fields. AB - The variation of wedge factor with field size was measured for a range of square and rectangular fields for 45 degrees and 60 degrees wedges. Measurements were performed on accelerators with both externally mounted wedges, the Varian 600C of nominal energy 6MV and internally mounted wedges, the Philips SL75/5 of nominal energy 6MV and the Philips SL25 of nominal energy 25MV. Analysis of the results confirm previous investigations reported in the literature of the variation of wedge factor with field size and in particular the significantly greater variation for internally mounted wedges. A wedge factor for a rectangular field based on the wedge factor of the open field equivalent square gives a maximum error of 1.5%. A wedge factor for a rectangular field based on the wedge factor of the square field of equal area reduces the maximum error to 0.5% for all three accelerators. Analysis of results reported in the literature show a similar reduction. PMID- 8198509 TI - Development and trial of a bovine herpesvirus 1-thymidine kinase deletion virus as a vaccine. AB - An Australian bovine herpesvirus 1 (BHV1) isolate with a defined (427 base pair) deletion in the protein coding region of the thymidine kinase gene was obtained by standard marker rescue procedures. After selection in the presence of the nucleotide analogue 5'-iodo-deoxy-uridine the virus was analysed by hybridisation with three differential oligonucleotide probes, restriction endonuclease profile studies and DNA sequence analysis. The virus elicited an immune response in recipient animals after either intramuscular or intravenous administration and produced no significant deleterious side-effects when administered at a dose sufficient to stimulate the host immune response. The safety and immunogenicity of the recombinant BHV1 virus 39B1 were similar to those reported for other registered BHV1 vaccines and the virus would appear to be suitable for the production of a vaccine seed lot and more exhaustive field trials as a prelude to commercial vaccine production and registration. PMID- 8198510 TI - The prevalence of lice (Bovicola ovis) infested sheep flocks in Western Australia (1987-1993) AB - The proportion of wool bale brands with a positive test for sheep lice in baled wool decreased from 29.5% in 1987/88 to 23.2% in 1990/91 before increasing to 38.2% in 1992/93. Changes in the proportion of wool bale brands with a positive test for lice were highly correlated with changes in the Wool Market Price Indicator. The increase in the proportion of positive lice tests since 1990/91 was associated with an increase in failures to eradicate lice from flocks. These failures were partly a consequence of the reduced use of lousicidal treatments, the development of resistance to synthetic pyrethroid chemicals and an increase in the transmission of lice between flocks. PMID- 8198511 TI - Reproductive performance in South Australian dairy herds. AB - Herd breeding records (161) were examined from a random 10% sample of dairy farms (96) in South Australia with more than 40 cows and suitable breeding records for 1988 and/or 1989. Of these farms, 53 (55.2%) had a year-round calving pattern, 42 (43.8%) claimed to be seasonal and one was changing from a year-round to a seasonal pattern. Only 14.6% of farmers observed oestrous behaviour outside milking times and 18.8% used tailpaint. Overall, the average proportion of unobserved heats was estimated to be 32%. Artificial insemination (AI) was carried out on 85.4% of farms (16.7% used AI alone and 68.7% also used bulls) of which 32.9% used commercial technicians and 67.1% were do-it-yourself operators. Overall, the average 30-day submission rate was 59.9% and the average 49-day non return to service rate was 58.9%. Investigation into the probable causes of suboptimal reproductive performance gave a tentative diagnosis of inefficient oestrous detection, deferral of service, inadequate nutrition, poor AI technique, insufficient bulls, and venereal/other diseases in 69.1, 32.1, 27.2, 28.4, 13.6 and 7.4% of records, respectively. PMID- 8198512 TI - Salmonella serovars and phage types in humans and animals in Australia 1987-1992. AB - This report summarises the range of Salmonella serovars and phage types found in humans in Australia during the years 1987 to 1992 inclusive, and compares them with serovars from food animals and raw meats for the same period. It also compares the major serovars found from different animal sources with their frequency from humans. The common serovars from animal feeds are compared with their frequency from animals. PMID- 8198513 TI - Caudal cruciate ligament avulsion fracture in a dog. PMID- 8198514 TI - Chronic intestinal pseudo-obstruction in a dog. AB - A three-year-old neutered female Border Collie was presented with inappetence, vomiting and diarrhoea. Abdominal radiographs revealed an obstructive pattern but no physical obstruction was evident at laparotomy. A diagnosis of chronic intestinal pseudo-obstruction was made based on histopathological changes in intestinal biopsies. Treatment was unsuccessful and the dog deteriorated progressively until euthanased five weeks after presentation. PMID- 8198515 TI - Efficacy of erythromycin compared with penicillin/streptomycin for the treatment of virulent footrot in sheep. PMID- 8198516 TI - Efficacy of permethrin in controlling the Australian paralysis tick Ixodes holocyclus and the cat flea Ctenocephalides felis on dogs. PMID- 8198517 TI - Failure to detect infection of the bovine foetus after inoculation of a prototype Australian strain of bovine herpesvirus 1. PMID- 8198518 TI - Importation of horses for special events. PMID- 8198519 TI - cDNA cloning and amino acid sequence of human mitochondrial delta 3 delta 2-enoyl CoA isomerase: comparison of the human enzyme with its rat counterpart, mitochondrial short-chain isomerase. AB - We report the isolation of a cDNA encoding a mature human monofunctional delta 3 delta 2-enoyl-CoA isomerase and the determination of its nucleotide sequence. The purified uncleaved protein, as well as several internal tryptic and CNBr fragments, were subjected to N-terminal peptide sequencing. The deduced amino acid sequence of the mature protein consists of 260 amino acids with a predicted M(r) of 28735. The human mitochondrial isomerase exhibits a 74% (78%) sequence identity with the corresponding rat counterpart at amino acid (nucleotide) level(s). Many basic amino acid residues in rat isomerase have been changed to acidic or neutral residues in human enzyme, explaining the differences observed between these proteins. PMID- 8198520 TI - Circular dichroism of stem bromelain: a third spectral class within the family of cysteine proteinases. AB - Two forms of stem bromelain (EC 3.4.22.4) were isolated from commercial, crude and chromatographically purified preparations of the enzyme by means of gel filtration and cation-exchange liquid chromatography. These forms possess nearly identical secondary and tertiary structures, as judged from their circular dichroism (c.d.) spectra. The spectral characteristics of stem bromelain suggest that this enzyme belongs to the alpha + beta protein class, as other cysteine proteinases do. In agreement with these results, quantitative estimation of secondary structures yielded amounts similar to those for papain and proteinase omega. However, the bromelain c.d. curve is clearly distinguishable from those reported for papain and proteinase omega, on one hand, and that of chymopapain, on the other. Thus, it is apparent that there are at least three types of c.d. spectra associated with the family of cysteine proteinases. PMID- 8198521 TI - Site-directed mutagenesis of rat muscle 6-phosphofructo-2-kinase/fructose-2,6 bisphosphatase: role of Asp-130 in the 2-kinase domain. AB - Asp-130 of the recombinant skeletal-muscle 6-phosphofructo-2-kinase (PFK 2)/fructose-2,6-bisphosphatase was mutated into Ala in order to study its role in catalysis and/or substrate binding. The D130A mutant displayed a 30- to 140-fold decreased 2-kinase Vmax, depending on the pH, and a 30- and 60-fold increase in Km for MgATP and Fru-6-P respectively at pH 8.5 compared with the wild-type. Mutagenesis of Asp-130 to Ala had no effect on the 2-phosphatase activity, and fluorescence measurements indicated that the changes in kinetic properties of PFK 2 in the D130A mutant were not due to instability. The role of Asp-130 in the 2 kinase reaction is discussed and compared with that of Asp-103 of 6-phosphofructo 1-kinase from Escherichia coli, which binds Mg2+. PMID- 8198522 TI - Regulation of aflatoxin B1-metabolizing aldehyde reductase and glutathione S transferase by chemoprotectors. AB - Ingestion of aflatoxin B1 (AFB1) represents a major risk factor in the aetiology of human hepatocellular carcinoma. In the rat, the harmful effects of AFB1 can be prevented by the administration of certain drugs which induce hepatic detoxification enzymes. We have previously shown that treatment of rats with the chemoprotector ethoxyquin (EQ) results in a marked increase in expression of the Alpha-class glutathione S-transferase (GST) Yc2 subunit which has high activity towards AFB1-8,9-epoxide [Hayes, Judah, McLellan, Kerr, Peacock and Neal (1991) Biochem. J. 279, 385-398]. To allow an assessment of whether the increased expression of GST Yc2 represents a general adaptive resistance mechanism to chemical stress, that is invoked by both chemoprotectors and carcinogens, we have examined the effects of EQ, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), phenobarbital (PB), AFB1, 3-methylcholanthrene (3-MC) and clofibrate on the AFB1-glutathione-conjugating activity and the GST subunit levels in rat liver. In addition, the effect of these drugs on the hepatic levels of an aldehyde reductase (AFB1-AR) that metabolizes the cytotoxic dialdehydic form of AFB1 has been studied as this enzyme also appears to be important in chemoprotection. Administration of the antioxidants EQ, BHA or BHT, as well as PB, led to a marked increase in levels of the GST Yc2 subunit in rat liver, and this increase coincided with a substantial rise in the GST activity towards AFB1 8,9-epoxide; neither AFB1, 3-MC nor clofibrate caused induction of Yc2 or any of the GST subunits examined. Among the xenobiotics studied, EQ was found to be the most effective inducing agent for the Yc2 subunit as well as Yc1, Yb1 and Yf. However, PB was equally as effective as EQ in increasing levels of the Ya-type subunits, although it was not found to be as potent an inducer of the other GST subunits, including Yc2. In addition to induction of GST, EQ caused a substantial increase in the hepatic content of AFB1-AR. Both BHA and BHT were also able to induce this enzyme but, by contrast, PB was found to be a poor inducer of AFB1 AR. AFB1, 3-MC and clofibrate were unable to serve as inducers of this reductase. The presence of Alpha-class GST, including the Yc2 subunit, was examined in various rat tissues. Constitutive expression of Yc2 was found in the epididymis at levels comparable with that observed in the liver from EQ-treated rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8198523 TI - Gene expression of GLUT3 glucose transporter regulated by glucose in vivo in mouse brain and in vitro in neuronal cell cultures from rat embryos. AB - This study was designed to determine whether glucose regulates the gene expression of glucose transporter GLUT3 in neurons. We examined the regulation of GLUT3 mRNA by glucose in vivo in mouse brain and in vitro by using neuronal cultures from rat embryos. Hypoglycaemia (< 30 mg/dl), produced by 72 h of starvation, increased GLUT3 mRNA in mouse brain by 2-fold. Hybridization studies in situ demonstrated that hypoglycaemia-induced increases in GLUT3 mRNA expression were observed selectively in brain regions including the hippocampus, dentate gyrus, cerebral cortex and piriform cortex, but not the cerebellum. Primary neuronal cultures from rat embryos deprived of glucose for 48 h also showed an increase (4-fold over control) in GLUT3 mRNA, indicating that glucose can directly regulate expression of GLUT3 mRNA. In contrast with hypoglycaemia, hyperglycaemia produced by streptozotocin did not alter the expression of GLUT3 mRNA. We also confirmed previous findings that hypoglycaemia increases GLUT1 mRNA expression in brain. The increase in GLUT1 expression was probably limited to the blood-brain barrier in vivo, since GLUT1 mRNA could not be detected in neurons of the mouse cerebrum. Thus we conclude that up-regulation of neuronal GLUT3 in response to glucose starvation represents a protective mechanism against energy depletion in neurons. PMID- 8198524 TI - ADP-ribosylation of Rho proteins by Clostridium botulinum exoenzyme C3 is influenced by phosphorylation of Rho-associated factors. AB - Specific [32P]ADP-ribosylation by Clostridium botulinum exoenzyme C3 was used to study the involvement of phosphorylation in the regulation of the low-molecular mass GTP-binding protein Rho. Dephosphorylation of CHO cell extracts by alkaline phosphatase treatment resulted in a 80-90% reduction in the C3-catalysed [32P]ADP ribosylation of Rho proteins in both cytosolic and membrane fractions. Similar results were obtained after dephosphorylation with protein phosphatase type-1 from bovine retina, whereas type-2B and type-2C phosphatases had no effect on the level of subsequent [32P]ADP-ribosylation of Rho by C3. Incubation of CHO cell lysate under phosphorylation conditions increased the subsequent C3-mediated [32P]ADP-ribosylation of Rho proteins. The protein kinase inhibitors H7 and H9 had no effect on [32P]ADP-ribosylation at concentrations which are specific for inhibition of protein kinase A or C. Recombinant glutathione S-transferase-RhoA fusion protein (GST-RhoA) was phosphorylated by protein kinase A; however, the phosphorylation had no stimulatory effect on the ADP-ribosylation of GST-RhoA by C3. An approx. 48 kDa phosphoprotein was identified which bound specifically to recombinant GST-RhoA fusion protein. By gel-permeation chromatography, Rho containing complexes of approx. 50 kDa and 130-170 kDa were detected. The ADP ribosylation of Rho in the 130-170 kDa complex was reduced by alkaline phosphatase pretreatment. The data suggest that Rho activity is influenced by phosphorylation of Rho-associated regulatory factors. Phosphorylation/dephosphorylation of these Rho-regulating factors appears to alter the ability of Rho to serve as a substrate for C3-induced [32P]ADP ribosylation. PMID- 8198525 TI - Synthesis, purification and kinetic properties of fluorescein-labelled penicillins. AB - The synthesis and properties of six fluorescein-labelled penicillins are reported. The two isomers of fluoresceyl-glycyl-6-amino-penicillanic acid are probably the best compounds to use for detection of all the penicillin-binding proteins (PBPs) present in a bacterial membrane preparation. However, the derivatives of ampicillin were much more efficient against Enterobacter aerogenes PBP3. The two isomers obtained when a commercial mixture of the two isomers of carboxyfluorescein was used most often exhibited similar properties, but the Streptomyces R61 extracellular DD-peptidase was only efficiently acylated by the 5'-carboxyfluorescein derivative of glycyl-6-aminopenicillanic acid. PMID- 8198526 TI - Evidence for a cell-specific negative regulatory element in the first intron of the gene for bovine elastin. AB - A cell-specific negative regulatory element has been identified in the first intron of the gene for elastin in a region between 442 and 464 bp from the translational start site. This regulatory element functions both when it is located 5' of the promoter and 3' of the chloramphenicol acetyltransferase (CAT) gene. The inhibition is observed both with the homologous elastin promoter and the heterologous SV1 promoter in transient expression experiments using rat aortic smooth-muscle cells. No inhibition was observed with NIH 3T3, Hep G2 and little, if any, with HeLa cells. Cell specificity was further confirmed by DNA mobility shift assays and the position of the negative regulatory element was localized with the use of synthetic duplex oligomers. It is proposed that this negative element plays a significant role in the modulation of the expression of the gene for elastin in the smooth-muscle cells of the aorta during development. PMID- 8198527 TI - Identification, purification and partial characterization of a carboxypeptidase from the matrix of rat liver mitochondria: a novel metalloenzyme. AB - A novel carboxypeptidase has been purified to apparent homogeneity from the matrix fraction of rat liver mitochondria by using a procedure mainly based on immobilized-metal-affinity chromatography (IMAC). This carboxypeptidase has been named mCP-III, since it represents the third major peak of carboxypeptidase activity after the IMAC step of purification. mCP-III hydrolyses a number of N blocked dipeptides, with preference for Cbz-Phe-Ala, and shows no degrading activity towards 125I-casein. The optimal pH of its activity is 7.6, the apparent Km for Cbz-Phe-Ala is 0.12 mM and the specific activity is 145.5 mumol/min per mg of protein. The enzyme is a typical metalloproteinase, is inhibited by 1,10 phenanthroline and carboxypeptidase inhibitor and re-activated by added Zn2+ and Co2+. The molecular mass estimated by molecular-sieve h.p.l.c. was approx. 115 kDa with two protein bands of 61 and 50 kDa shown by SDS/PAGE analysis, indicating that the enzyme is active as a dimer. This is the first clearly identified carboxypeptidase within mitochondria. PMID- 8198528 TI - The actin-activated ATPase of co-polymer filaments of myosin and myosin-rod. AB - The actin activated ATPase of myosin at low ionic strength shows a complex dependence on actin concentration, in contrast with the simple hyperbolic actin activation kinetics of heavy meromyosin and subfragment-1. To investigate how the aggregation of myosin influences the actomyosin ATPase kinetics, we have studied the actin-activated ATPase of mixed filaments in which the myosin molecules are separated from each other by copolymerization with myosin rod. Electron microscopy of copolymer filaments, alone and bound to actin, indicates that the myosin heads are distributed randomly along the co-polymer filaments. The actin activated ATPase of myosin decreases with increasing rod, approaching a plateau of about 30% of the control at a rod/myosin molar ratio of 4:1. The decrease in ATPase persists even at Vmax, the extrapolated limit at infinite actin, indicating that it is not due merely to the loss of cooperative actin binding. Furthermore, the actin dependence of the ATPase still shows a biphasic character like that of control myosin, even at rod/myosin ratio of 12:1, so this complexity is not probably due solely to the structural proximity of myosin molecules, but may involve a non-equivalence of myosin heads or myosin molecules in the filament environment. PMID- 8198529 TI - The analysis of rate limitation within enzymes: relations between flux control coefficients of rate constants and unidirectional rates, rate constants and thermodynamic parameters of single isolated enzymes. AB - The extent to which a rate constant or step within an enzyme mechanism limits the net enzyme rate in a particular condition can be quantified as a flux control coefficient. We derive here a number of relations between the control coefficients and the unidirectional rates, rate constants, and thermodynamic parameters of the enzyme. These and other relations are used to suggest a number of methods for experimentally measuring control coefficients within enzymes. PMID- 8198530 TI - Localized chemical reactivity in DNA associated with the sequence-specific bisintercalation of echinomycin. AB - Four complementary footprinting and probing techniques utilizing DNAse I, methidiumpropyl EDTA (MPE).FeII, diethyl pyrocarbonate (DEPC) and KMnO4 as DNA cleaving or DNA-modifying agents have been applied to investigate the sequence specific binding to DNA of the antitumour antibiotic echinomycin. A 265 bp EcoRI PvuII DNA restriction fragment excised from plasmid pBS was used as a substrate. Six regions of protection against DNAase I cleavage were located on the 265-mer: three sites encompass the sequences 5'-TCGA or 5'-GCGT and the three others contain 5'-GpG (CpC) dinucleotide sequences where the inhibition of DNAase I cutting by echinomycin is less pronounced. In contrast, MPE.FeII cleavage allows identification of only three echinomycin-binding sites on the 265-mer: two sites contain the sequence 5'-TCGA and one encompasses the sequence 5'-ACCA. Cleavage of DNA by MPE.FeII in the presence of echinomycin remains practically unaffected at the sequence 5'-GCGT, despite its identification by DNAase I as a strong site for binding the antibiotic, as well as at the two other sequences containing GpG steps. With both DNAase I and MPE.FeII, enhanced DNA cleavage is evident at AT rich sequences in the presence of echinomycin. Enhanced reactivity towards KMnO4 and DEPC provides clear evidence for sequence-dependent conformational changes in DNA induced by the antibiotic. The experiments reveal that KMnO4 reacts most strongly with thymines located around, but not necessarily adjacent to, an echinomycin-binding site, whereas the carbethoxylation reactions caused by DEPC occur primarily at the adenine residues lying immediately 5' or 3' to the dinucleotide that denotes an echinomycin-binding site. The results reported here demonstrate that DEPC and KMnO4 serve as sensitive probes for different states of the DNA helix. It seems that the reaction with KMnO4 involves transient unstacking events, whereas the carbethoxylation reaction of DEPC requires larger scale helix opening. PMID- 8198531 TI - Replacement of enzyme-bound calcium with strontium alters the kinetic properties of methanol dehydrogenase. AB - Methanol dehydrogenase (MEDH) possesses tightly bound Ca2+ in addition to its pyrroloquinoline quinone (PQQ) prosthetic group. Ca2+ was replaced with Sr2+ by growing the host bacterium, Paracoccus denitrificans, in media in which Ca2+ was replaced with Sr2+. MEDH, which was purified from these cells (Sr-MEDH), exhibited an increased absorption coefficient for the PQQ chromophore, and displayed certain kinetic properties which were different from those of native MEDH. Native MEDH exhibits an endogenous activity which is not stimulated by substrate and which is inhibited by cyanide. Sr-MEDH exhibited lower endogenous activity which was stimulated by substrate, and was much less sensitive to inhibition by cyanide. The Vmax. for the methanol-dependent activity of Sr-MEDH was 3-fold greater than that of the native enzyme, and the Ks for methanol was altered. Cyanide also acts as an obligatory activator and competitive inhibitor of methanol-dependent activity in native MEDH from P. denitrificans [Harris and Davidson (1993) Biochemistry 32, 4362-4368]. Sr-MEDH exhibited a similar K1 for cyanide inhibition of methanol-dependent activity, but the KA for cyanide activation of this activity was 17-fold greater than that for the native enzyme. The activation energy of Sr-MEDH was 13.4 kJ (3.2 kcal)/mol lower than that of the native enzyme. These data confirm and significantly extend the conclusions from genetic [Richardson and Anthony (1992) Biochem. J. 287, 709-715] and crystallographic [White, Boyd, Mathews, Xia, Dai, Zhang and Davidson (1993) Biochemistry 32, 12955-12958] studies that suggest an apparently unique role for Ca2+ in MEDH compared with other Ca(2+)-dependent proteins and enzymes. PMID- 8198532 TI - The green alga Scenedesmus obliquus contains both diadenosine 5',5'''-P1,P4 tetraphosphate (asymmetrical) pyrophosphohydrolase and phosphorylase activities. AB - Diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) phosphorylase and Ap4A pyrophosphohydrolase activities have been purified from extracts of the green alga Scenedesmus obliquus. Both activities were also detected in Scenedesmus brasiliensis, Scenedesmus quadricauda and in Chlorella vulgaris. This is the first time that both types of enzyme have been detected in the same species. The Ap4A phosphorylase has a molecular mass of 46-48 kDa, a broad pH optimum between 7.5 and 9.5, and requires a divalent ion for activity (Mg2+ > Co2+ > Ca2+ = Mn2+ = Cd2+ > Zn2+). It degrades substrates with at least four phosphate groups and always produces a nucleoside 5'-diphosphate product. The Km values for Ap4A and Pi are 5.3 microM and 160 microM, respectively, and kcat. = 1.8 s-1. Arsenate, vanadate, molybdate, chromate and tungstate can substitute for phosphate. The enzyme also catalyses Ap4A synthesis (Keq. = [Ap4A] [Pi]/[ATP][ADP] = 9 x 10(-4)) and ADP arsenolysis. The Ap4A hydrolase has a molecular mass of 26-28 kDa, an alkaline pH optimum of 8.8-9.8, and prefers Zn2+ as the stimulatory ion (Zn2+ > Mg2+ > Mn2+ > Co2+ > Cd2+). It degrades substrates with at least four phosphate groups, having a slight preference for Ap5A, and always produces a nucleoside 5' triphosphate product. The Km value for Ap4A is 6.6 microM and kcat. = 1.3 s-1. It is inhibited competitively by adenosine 5'-tetraphosphate (Ki = 0.67 microM) and non-competitively by fluoride (Ki = 150 microM). A 50-54 kDa dinucleoside 5',5''' P1,P3-triphosphate (Ap3A) pyrophosphohydrolase was also detected in S. obliquus, S. quadricauda and C. vulgaris. The corresponding enzyme in S. brasiliensis (> 100 kDa) may be a dimer PMID- 8198533 TI - Targeting of passenger protein domains to multiple intracellular membranes. AB - The role of passenger domains in protein targeting was examined by fusing previously characterized targeting motifs to different protein sequences. To compare the targeting requirements for a variety of subcellular compartments, targeting of the fusion proteins was examined for endoplasmic reticulum, mitochondria and peroxisomes in vitro and in yeast. Although most passenger domains were only partially passive to translocation, motif-dependent targeting via motifs positioned at either end of one passenger domain (gPA) was demonstrated for all of the subcellular compartments tested. The data presented extend earlier suggestions that translocation competence is an intrinsic property of the passenger protein. However, the properties that determine protein targeting are not mutually exclusive for the compartments tested. Therefore, although the primary determinant of specificity is the targeting motif, our results suggest that translocation competence of the targeted protein augments the fidelity of transport. PMID- 8198534 TI - Regulation of heat shock protein synthesis by quercetin in human erythroleukaemia cells. AB - Synthesis of heat-shock proteins (HSPs) is universally induced in eukaryotic and prokaryotic cells by exposure to elevated temperatures or to other types of environmental stress. In mammalian cells, HSPs belonging to the 70 kDa family (HSP70) have a regulatory role in several cellular processes, and have been shown to be involved in the control of cell proliferation and differentiation. Although many types of HSP70 inducers have been identified, only a few compounds, all belonging to the flavonoid group, have been shown to inhibit HSP70 induction. Because inhibitors of HSP70 synthesis could be an important tool with which to study the function of this protein, we have investigated the effect of quercetin, a flavonoid with antiproliferative activity which is widely distributed in nature, on HSP70 synthesis in human K562 erythroleukaemia cells after treatment with severe or mild heat shock and with other inducers. Quercetin was found to affect HSP70 synthesis at more than one level, depending on the conditions used. Indeed, after severe heat shock (45 degrees C for 20 min) treatment with quercetin, at non-toxic concentrations, was found to inhibit HSP70 synthesis for a period of 3-4 h. This block appeared to be exerted at the post-transcriptional level and to be cell-mediated, as the addition of quercetin during translation of HSP70 mRNA in vitro had no effect. After prolonged (90 min) exposure at 43 degrees C, however, quercetin was found to inhibit also HSP70 mRNA transcription. Pretreatment of K562 cells with quercetin had no effect on HSP70 expression, and quercetin needed to be present during induction to be effective. Under all conditions tested, the quercetin-induced block of HSP70 synthesis was found to be transient and, after an initial delay, synthesis of HSP70 reached the control rate and continued at the same level for several hours after the time at which HSP70 synthesis had been turned off in control cells. Finally, inhibition of HSP70 synthesis by quercetin appeared to be dependent on the temperature used and on the type of stressor. PMID- 8198535 TI - Carbachol activates protein kinase C in dispersed gastric chief cells. AB - We used an 'in situ' kinase assay to examine agonist-induced protein kinase C. (PKC) activation in dispersed chief cells from guinea-pig stomach. Phorbol 12 myristate 13-acetate (PMA), a phorbol ester, and carbamoylcholine, a cholinergic agent, caused a 4- and 3-fold increase in pepsinogen secretion from dispersed chief cells respectively. Whereas PMA caused a rapid 3-fold increase in peptide kinase activity, carbachol caused a 15% increase in activity that was inhibited by the PKC inhibitor, CGP 41,251. Concentrations of carbamoylcholine and a Ca2+ ionophore that were sub-maximal for stimulation of pepsinogen secretion did not cause PKC activation. These results indicate that, in the absence of PKC activation, other mechanisms, most likely involving changes in cellular Ca2+, are sufficient to stimulate pepsinogen secretion. Nevertheless, carbamoylcholine stimulated maximal secretion of pepsinogen only at concentrations that also resulted in activation of PKC. Moreover, these data indicate that relatively small increases in PKC activity (5-10%) can stimulate pepsinogen secretion from dispersed chief cells. PMID- 8198536 TI - Actions of the creatine analogue beta-guanidinopropionic acid on rat heart mitochondria. AB - The action of the creatine analogue beta-guanidinopropionic acid (beta-GPA) was examined in rat heart mitochondria and in isolated cardiomyocytes or fibres which were permeabilized with the non-ionic detergent saponin to determine the kinetics of mitochondrial creatine kinase for beta-GPA. Fibres and myocytes were subjected to increasing [ADP] in the presence and absence of beta-GPA or creatine, whereas isolated mitochondria received a similar protocol with increasing [ATP]. In isolated mitochondria given ATP, there was a stimulation of respiration by creatine, but no significant stimulation of respiration by beta-GPA. Further studies on fibres from control and beta-GPA-fed rats also found that beta-GPA is not utilized by the mitochondria, as evidenced by a lack of beta-GPA-stimulated respiration (Km for ADP = 142 +/- 23 microM) compared with control (Km for ADP from 161 +/- 23 microM), but no significant change in Vmax. Therefore the rat heart mitochondria are not responsive to beta-GPA as compared with creatine. Interestingly, the fibres from beta-GPA-fed rats had no creatine- or beta-GPA stimulated respiration (Km for ADP = 57.3 +/- 7.2 microM for control, 54.2 +/- 7.2 microM with creatine, and 53.5 +/- 7.8 microM with beta-GPA). The mitochondria prepared from the hearts of rats exposed for 10 weeks to 1% beta-GPA in their diet had a significant decrease in Vmax. and a significant decrease in Km for ADP. Thus the hearts from beta-GPA-fed animals may be pathologic, due to a disruption of the creatine kinase energy circuit. PMID- 8198537 TI - Exocytosis in chromaffin cells: evidence for a MgATP-independent step that requires a pertussis toxin-sensitive GTP-binding protein. AB - We have previously described that mastoparan, an amphiphilic tetradecapeptide that activates heterotrimeric G-proteins, inhibits Ca(2+)-induced MgATP-dependent secretion from streptolysin-O-permeabilized chromaffin cells [Vitale, Mukai, Rouot, Thierse, Aunis and Bader (1993) J. Biol. Chem. 268, 14715-14723]. Our observations suggest the involvement of an inhibitory G(o)-protein, possibly located on the membrane of secretory granules, in the final stages of the exocytotic pathway in chromaffin cells. Here, we demonstrate that mastoparan is also able to stimulate the Ca(2+)-dependent secretion of catecholamines in the absence of MgATP in the medium. This MgATP-independent secretion is totally blocked by tetanus toxin, a potent inhibitor of exocytosis in all neurosecretory cells so far investigated, suggesting that the mastoparan target is a component of the exocytotic machinery. Mas17, a mastoparan analogue inactive on G-proteins, had no effect on catecholamine secretion whereas both Mas7, a highly active analogue of mastoparan, and AlF4-, which selectively activates trimeric G proteins, triggered MgATP-independent secretion. Non-hydrolysable GTP analogues (GTP[S] and p[NH]ppG) mimicked the dual effects of mastoparan on secretion: they inhibited exocytosis in the presence of MgATP and stimulated MgATP-independent secretion. The different potencies displayed by these two analogues suggest the involvement of two distinct G-proteins. Accordingly, the mastoparan-induced MgATP independent secretion is highly sensitive to pertussis toxin (PTX) whereas the inhibition by mastoparan of secretion in the presence of MgATP is resistant to PTX treatment. When permeabilized cells were incubated with mastoparan, the release of arachidonic acid increased in a PTX-sensitive manner. 7,7-Dimethyl-5,8 eicosadienoic acid, a potent inhibitor of intracellular phospholipase A2, inhibited both the arachidonate release and the MgATP-independent catecholamine secretion evoked by mastoparan. In contrast, neomycin, an inhibitor of phospholipase C, had no significant effect on either the release of arachidonic acid or the secretion of catecholamines provoked by mastoparan. We conclude that two distinct heterotrimeric G-proteins act in series in the exocytotic pathway in chromaffin cells: one controls an ATP-dependent priming step through an effector pathway that remains to be determined, and the second is involved in a late Ca(2+)-dependent step which does not require MgATP but possibly involves the generation of arachidonic acid. PMID- 8198538 TI - Use of glycyl-L-phenylalanine 2-naphthylamide, a lysosome-disrupting cathepsin C substrate, to distinguish between lysosomes and prelysosomal endocytic vacuoles. AB - Lysosome-disrupting enzyme substrates have been used to distinguish between lysosomal and prelysosomal compartments along the endocytic pathway in isolated rat hepatocytes. The cells were incubated for various periods of time with 125I labelled tyramine cellobiose (125I-TC) covalently coupled to asialoorosomucoid (AOM) (125I-TC-AOM); this molecule is internalized by receptor-mediated endocytosis and degraded in lysosomes, where the degradation products (acid soluble, radio-labelled short peptides) accumulate, Glycyl-L-phenylalanine 2 naphthylamide (GPN) and methionine O-methyl ester (MOM), which are hydrolysed by lysosomal cathepsin C and a lysosomal esterase respectively, both diffused into hepatocytic lysosomes after electrodisruption of the cells. Intralysosomal accumulation of the hydrolysis products (amino acids) of these substrates caused osmotic lysis of more than 90% of the lysosomes, as measured by the release of acid-soluble radioactivity derived from 125I-TC-AOM degradation. The acid-soluble radioactivity coincided in sucrose-density gradients with a major peak of the lysosomal marker enzyme acid phosphatase at 1.18 g/ml; in addition a minor, presumably endosomal, acid phosphatase peak was observed around 1.14 g/ml. The major peak of acid phosphatase was almost completely released by GPN (and by MOM), while the minor peak seemed unaffected by GPN. Acid-insoluble radioactivity, presumably in endosomes, banded (after 1 h of 125I-TC-AOM uptake) as a major peak at 1.14 and a minor peak at 1.18 g/ml in sucrose gradients, and was not significantly released by GPN. GPN thus appears to be an excellent tool by which to distinguish between endosomes and lysosomes. MOM, on the other hand, released some radioactivity and acid phosphatase from endosomes as well as from lysosomes. PMID- 8198539 TI - Surfactant protein D binding to alveolar macrophages. AB - Surfactant protein D (SP-D) is a lung-specific protein, synthesized and secreted by lung epithelial cells. It belongs to group III of the family of C-type lectins; each member of this group has an unusual overall structure consisting of multiple globular 'head' regions (which contain the C-type lectin domains) linked by triple-helical, collagen-like, strands. This group includes the surfactant protein A (SP-A) and the serum proteins mannan-binding protein, conglutinin and collectin-43, all of which have been shown to bind to the C1q receptor found on a wide variety of cells, including macrophages. Both SP-D and SP-A have been shown to enhance oxygen radical production by alveolar macrophages. Although this strongly suggests a direct interaction between SP-D and a specific receptor on alveolar macrophages, it is still unclear whether SP-D binds to the same receptor used by SP-A and/or C1q. Human SP-D was isolated from amniotic fluid and was radiolabelled using 125I. Alveolar macrophages were isolated from human bronchioalveolar lavage fluid, and also from bovine lung washings, by differential adhesion to 24-well tissue-culture plates. The study was carried out using EDTA-containing buffers, to eliminate Ca(2+)-dependent C-type lectin binding, and was also carried out at 4 degrees C to eliminate possible internalization by the cells. 125I-SP-D showed specific binding to alveolar macrophages in both a time- and concentration-saturable manner. The binding was inhibited, by approx. 90%, on addition of a 200-fold excess of unlabelled SP-D. The apparent dissociation constant (Kd) was (3.6 +/- 1.3) x 10(-11) M, based on the assumption that native SP-D is assembled as a dodecamer of 12 identical polypeptides of 43 kDa to yield a protein of 516 kDa. C1q was also shown to bind alveolar macrophages (Kd 3 x 10(-6) M), but addition of C1q did not show inhibition of the binding of 125I-SP-D to the macrophages. We conclude that SP-D binds specifically to alveolar macrophages and the receptor involved is different from that utilized by C1q. PMID- 8198540 TI - Glucose oxidation and low-density lipoprotein-induced macrophage ceroid accumulation: possible implications for diabetic atherosclerosis. AB - The exposure of proteins to high concentrations of glucose in vitro is widely considered a relevant model of the functional degeneration of tissue occurring in diabetes mellitus. In particular, the enhanced atherosclerosis in diabetes is often discussed in terms of glycation of low-density lipoprotein (LDL), the non enzymic attachment of glucose to apolipoprotein amino groups. However, glucose can undergo transition-metal-catalysed oxidation under near-physiological conditions in vitro, producing oxidants that possess a reactivity similar to the hydroxyl radical. These oxidants can fragment protein, hydroxylate benzoic acid and induce lipid peroxidation in human LDL. In this study, glycation of LDL in vitro is accompanied by such oxidative processes. However, the oxidation of LDL varies with glucose concentration in a manner which does not parallel changes in protein glycation. Glycation increases in proportion to glucose concentration, whereas in our studies maximal oxidation occurs at a glucose concentration of approx. 25 mM. The modification of LDL resulting from exposure to glucose alters macrophage ceroid accumulation, a process which occurs in the human atherosclerotic plaque. The accumulation of ceroid in macrophages is shown to be related to LDL oxidation rather than LDL glycation, per se, as it too occurs at a maximum of approx. 25 mM. Oxidative sequelae of protein glycation appear to be a major factor in LDL-macrophage interactions, at least with respect to ceroid accumulation. Our observations are discussed in the context of the observed increase in the severity of atherosclerosis in diabetes. PMID- 8198541 TI - Probing the active site of cytoplasmic aldehyde dehydrogenase with a chromophoric reporter group. AB - 3,4-Dihydro-3-methyl-6-nitro-2H-1,3-benzoxazin-2-one ('DMNB') reacts with cytoplasmic aldehyde dehydrogenase in a similar way to that previously observed with the structurally related p-nitrophenyl dimethylcarbamate, but provides a covalently linked p-nitrophenol-containing reporter group at the enzyme's active site. The pKa of the enzyme-linked reporter group is much higher than that of free p-nitrophenol, which is consistent with its being in a very hydrophobic environment, or possibly one containing negative charge. Upon binding of NAD+ to the modified enzyme, the pKa falls dramatically, by about 4 1/2 pH units. This implies that under these conditions there is a positive charge near the p nitrophenoxide moiety, perhaps that of the nicotinamide ring of NAD+. The modified enzyme binds NAD+ very tightly; neither gel filtration nor dialysis is effective in separating them. However, the reporter group provides a convenient way of monitoring the displacement of this bound NAD+ when NADH is added. PMID- 8198542 TI - Regulation of fibrinolysis by non-esterified fatty acids. AB - The ability of oleic acid to modulate fibrinolysis was measured by following the urokinase-mediated and plasminogen-dependent cleavage of 125I-labelled fibrin clots. Oleic acid levels within the physiological range exerted a concentration dependent inhibition of urokinase-mediated fibrinolytic activity. SDS/PAGE revealed that oleic acid enhances urokinase activity but simultaneously increases the autolytic cleavage of the newly formed low-molecular-mass subunit of plasmin. Oleic acid-induced cleavage of this subunit containing the catalytic site of plasmin was suppressed by the plasmin substrate H-D-valyl-L-leucyl-L-lysine-p nitroanilide (S-2251) and was prevented by alpha 2-antiplasmin. A concentration dependent inhibition of the activity of purified plasmin on 125I-labelled fibrin clot was also observed; 93% and 50% inhibition was noted with 150 microM and 32 microM oleic acid respectively. Oleic acid at 200 microM also effectively displaced plasmin prebound to a polylysine-Sepharose column. Examination of the fatty acid specificity showed that a minimal chain length of 16 carbon atoms and the presence of at least one double bond, preferably in a cis configuration, were required for inhibition of the fibrinolytic activity of plasmin. Oleic acid at a concentration that produced only a minimal inhibition of plasmin activity induced a marked inhibition by palmitic acid, while palmitic acid alone is ineffective. The findings suggest that oleic acid stimulates plasminogen activation and modulates the fibrinolytic and autolytic activities of plasmin. PMID- 8198543 TI - Regulation of rat mammary-gland uptake of orally administered [1-14C]triolein by insulin and prolactin: evidence for bihormonal control of lipoprotein lipase activity. AB - The effects of insulin deficiency (streptozotocin-induced) or insulin plus prolactin deficiency on the disposal of orally administered [1-14C]triolein between oxidation to 14CO2, uptake by mammary gland and transfer to suckling pups were studied. Insulin deficiency decreased mammary-gland total weight (by 40%), but caused no change in total tissue DNA. A greater proportion of the [1 14C]triolein was oxidized to 14CO2 (120% increase) in the insulin-deficient rats, and there was a tendency for total transfer of [14C]lipid to mammary gland and suckling pups to be decreased. A parallel decrease in total mammary-tissue lipoprotein lipase activity occurred. Combined hormone deficiency caused more dramatic changes in all parameters measured. Replacement of insulin (24 h) in insulin-deficient rats decreased 14CO2 production, increased the uptake of [14C]lipid into the mammary gland and tended to increase total lipoprotein lipase activity. In contrast, administration of prolactin to insulin-deficient rats had no effect on any of the parameters measured. Replacement of insulin (24 h) in the combined hormone-deficient rats increased uptake of [14C]lipid and lipoprotein lipase approx. 3-fold, whereas prolactin again had no significant effects. Replacement of both hormones increased (6-fold) transfer of [14C]lipid to the pups, but did not increase overall uptake of [14C]lipid (mammary gland, milk clot and pups) above the value for insulin alone. It is concluded that insulin is the primary regulator of triacylglycerol uptake and of lipoprotein lipase activity in the lactating mammary gland of the rat and that the action of prolactin on these processes is indirect. Prolactin, but not insulin, appears to have a direct effect on milk lipid transfer to pups. PMID- 8198544 TI - Regulation of fos-lacZ fusion gene expression in primary mouse epidermal keratinocytes isolated from transgenic mice. AB - The expression of a fos-lacZ fusion gene was studied in primary mouse epidermal keratinocytes obtained from transgenic mice. This gene construct contains the entire upstream regulatory sequence of c-fos, and expression of the endogenous and fusion gene was shown by Northern analysis to correlate upon induction with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). Using a chromogenic substrate of beta-galactosidase, we also demonstrated that expression of the fusion gene product, like that of Fos, was localized to the cell nucleus. In addition, we showed that epidermal keratinocytes responded to dialysed fetal bovine serum (FBS), TPA and high-calcium medium with enhanced Fos-lacZ expression and an inhibition of proliferation. The time course of induction of Fos-lacZ expression was similar for dialysed FBS and TPA, with a peak approximately 2 h after exposure. Exposure for approximately 24 h to an elevated extracellular calcium concentration was required to elicit an increase in Fos-lacZ expression. The lack of an immediate effect of raising medium calcium levels on Fos-lacZ expression contrasted with the rapidity of its effect on DNA synthesis, which was significantly inhibited within 6-8 h. In addition, we found that the protein kinase C inhibitor Ro 31-7549 blocked Fos-lacZ expression induced by TPA but had little or no effect on that elicited by high calcium levels. Thus, although our results indicate that the fos gene product may be involved in mediating epidermal keratinocyte growth arrest in response to differentiative agents such as FBS, TPA and high medium calcium levels, the exact role of this gene product remains unclear. PMID- 8198545 TI - Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. AB - In humans, glutathione-dependent conjugation of halomethanes is polymorphic, with 60% of the population classed as conjugators and 40% as non-conjugators. We report the characterization of the genetic polymorphism causing the phenotypic difference. We have isolated a cDNA that encodes a human class Theta GST (GSTT1) and which shares 82% sequence identity with rat class Theta GST5-5. From PCR and Southern blot analyses, it is shown that the GSTT1 gene is absent from 38% of the population. The presence or absence of the GSTT1 gene is coincident with the conjugator (GSST1+) and non-conjugator (GSTT1-) phenotypes respectively. The GSTT1+ phenotype can catalyse the glutathione conjugation of dichloromethane, a metabolic pathway which has been shown to be mutagenic in Salmonella typhimurium mutagenicity tester strains and is believed to be responsible for carcinogenicity of dichloromethane in the mouse. In humans, the enzyme is found in the erythrocyte and this may act as a detoxification sink. Characterization of the GSTT1 polymorphism will thus enable a more accurate assessment of human health risk from synthetic halomethanes and other industrial chemicals. PMID- 8198546 TI - A structure-effect study of the induction by polyamines of the transport in vitro of the precursor of ornithine transcarbamylase. AB - Polyamines induce the transport in vitro of the precursor of ornithine transcarbamylase (pOTC) into isolated rat liver mitochondria by facilitating its functional binding to these organelles. Comparative studies of the effect on the in vitro transport of pOTC of polyamine derivatives and related compounds have allowed us to establish that: (i) at least two protonated amino groups per molecule are necessary to induce the pOTC transport; (ii) a distance of three CH2- groups between the amino groups in diamines is enough to induce this effect, although no differences were observed with diamines having distances of three to eight -CH2- groups. Longer distances resulted in a marked decrease of the effect. PMID- 8198547 TI - NN-dimethyl-1,4-phenylenediamine as an alternative reductant for peptidylglycine alpha-amidating mono-oxygenase catalysis. AB - C-terminal alpha-amidation is a structural feature essential to the biological activity of many peptide hormones. Peptidylglycine alpha-amidating mono-oxygenase (PAM; EC 1.14.17.3) catalyses conversion of glycine-extended peptide hormone precursors into their corresponding alpha-hydroxyglycine derivatives. This reaction is the first step in the C-terminal amidation process. We report here that in the presence of molecular O2, copper and PAM substrate, NN-dimethyl-1,4 phenylenediamine (DMPD) serves as the requisite electron donor for the mono oxygenase, being oxidized in the process to a stable and highly chromophoric cation radical. By monitoring the rate of increase in absorbance at 515 nm, PAM activity can be easily followed. This provides a spectrophotometric assay for PAM, which represents the first continuous assay reported for this enzyme. DMPD supported PAM-catalysed mono-oxygenation exhibits normal Michaelis-Menten kinetic behaviour. Steady-state kinetic studies established that both the ascorbate supported and DMPD-supported PAM reactions exhibit apparent 'Ping Pong' kinetics. In addition, both electron donors give rise to similar pH profiles and identical inhibition patterns towards known competitive inhibitors of PAM. The stoichiometry between formation of the DMPD cation radical and the alpha hydroxyglycine PAM product was determined to be 2:1, the value expected for a monooxygenase-catalysed reaction. The optimum pH for the DMPD-supported continuous PAM assay was found to be about 5.5. The major advantage of this assay over all previously reported methods is that it is continuous; thus accurate initial rates are easily obtained. Moreover, unlike previous assay methods, 125I labelled or chromophorically modified substrates are not required. Kinetic parameters for a broad range of PAM substrates and inhibitors have been successfully obtained using this assay. PMID- 8198548 TI - Expression of rat endopeptidase-24.18 in COS-1 cells: membrane topology and activity. AB - Endopeptidase-24.18 (E-24.18; EC 3.4.24.18) is a metallopeptidase of the astacin family and is highly expressed in kidney brush-border membranes of rodents. Rat E 24.18 consists of two disulphide-linked alpha/beta dimers [(alpha/beta)2]. In order to investigate the mechanisms of assembly and the importance of each subunit in the enzymic process, the cloned cDNAs for the rat alpha and beta subunits were transiently expressed either alone or together in COS-1 cells. Immunoblotting of cell extracts and spent culture media showed that, when expressed alone, the alpha subunit is secreted, whereas the beta subunit is membrane-bound. In alpha/beta-transfected cells, the alpha subunit remained membrane-bound, but could be released from the cell surface after papain treatment or after incubation with 10 mM dithiothreitol. Furthermore, mutants of the alpha subunit in which the putative C-terminal anchor domain was deleted could still form cell-associated alpha/beta dimers. These results are consistent with a topological model of E-24.18 in which the beta subunit is anchored in the plasma membrane and the alpha subunit is retained at the cell surface through disulphide bridge(s) with the beta subunit. Both the alpha and beta recombinant subunits expressed in COS-1 cells showed little azocasein-degrading activity. However, activity of either individual subunits of alpha/beta dimers was increased after mild trypsin digestion, suggesting that in COS-1 cells the enzymes are synthesized as zymogens. Finally, inactivation of the alpha subunit by site-directed mutagenesis of Glu-157, which is believed to play a role in catalysis, showed that both subunits participate in the enzymic activity of the heterodimer. PMID- 8198549 TI - Osmotically inducible uptake of betaine via amino acid transport system A in SV 3T3 cells. AB - The osmotically inducible uptake of betaine (NNN-trimethylglycine) by SV-3T3 cells has been studied and compared with the similar process in MDCK cells. Betaine uptake by SV-3T3 cells could be described in terms of a saturable, Na(+) dependent, component plus a small non-saturable, Na(+)-independent, component. Transport was active, producing considerable accumulation of betaine in the cells. After exposure of the cells to hypertonic conditions for 6 h, there was a marked increase in betaine uptake. Kinetic analysis indicated that this increase resulted from an increase in the Vmax. value of the saturable component, from about 88 to 185 nmol of betaine/5 min per mg of protein, the corresponding Km values of about 15 and 10 mM not being significantly different. This induction of transport activity was detectable only after about 2 h exposure of the cells to hypertonic medium, closely paralleling an induction of influx of N methylaminoisobutyric acid, and was prevented by the presence of cycloheximide. Betaine influx was markedly inhibited by several neutral amino acids, particularly those transported by system A, such as N-methylaminoisobutyric acid and the imino acid proline. A high concentration (25 mM) of betaine also significantly inhibited the uptake of proline by SV-3T3 cells. Although very similar results were obtained with MDCK cells, prolonged exposure of cells to hypertonic conditions revealed distinct differences. When the hypertonic incubation was extended from 6 h to 24 h, betaine transport in SV-3T3 cells either remained the same or decreased, whereas it showed a further marked increase in MDCK cells, and also became sensitive to inhibition by gamma aminobutyric acid. mRNA for the betaine transporter BGT-1 [Yamauchi, Uchida, Kwon, Preston, Brooks Robey, Garcia-Perez, Burg and Handler (1992) J. Biol. Chem. 267, 649-652] was detectable in MDCK cells exposed to hypertonic medium for 24 h, but not in SV-3T3 cells under any conditions. It is concluded that SV-3T3 cells do not produce a specific inducible transporter analogous to BGT-1, but they can accumulate betaine via the amino acid transport system A. PMID- 8198550 TI - Membrane-associated diacylglycerol kinase activity is increased by noradrenaline, but not by angiotensin II, in arterial smooth muscle. AB - In rat small arteries, noradrenaline stimulates the sustained production of arachidonoyl-phosphatidic acid, whereas there is only a slight and transient increase with angiotensin II [Ohanian, Ollerenshaw, Collins and Heagerty (1990) J. Biol. Chem. 265, 8921-8928]. Diacylglycerol kinase (DGK) is the enzyme responsible for generating phosphatidic acid from 1,2-diacylglycerol (DAG). To investigate whether agonists influence DGK activity, we have studied this enzyme in both particulate and soluble fractions prepared from rat small arteries. Soluble DGK activity was inhibited by octyl glucoside. Therefore a deoxycholate assay was used for this fraction, whereas an octyl glucoside mixed-micelle assay was used to examine particulate fractions. Particulate DGK selectively phosphorylated long-chain DAG at a rate 2.5-3-fold higher than that for the synthetic substrate dioctanoylglycerol. In contrast, the substrate preference of the soluble isoenzyme(s) was: dioctanoylglycerol > arachidonoyl-DAG= dioleoylglycerol. Stimulation of intact arteries with noradrenaline (15 microM) increased membrane-associated DGK activity 3-fold, transiently. Angiotensin II (100 nM) stimulation did not alter the DGK activity of this fraction. The activity of the soluble DGK was increased by both agonists, but only transiently. These results demonstrate that rat small arteries contain a membrane-associated DGK which metabolizes arachidonoyl-containing substrate. Also, the activity of this enzyme is regulated differentially by vasoconstrictor hormones. It is concluded that modulation of DGK activity may represent one point at which agonists using the same signal-transduction pathway may tailor the cellular response. PMID- 8198551 TI - Levels of the conversion endoproteases PC1 (PC3) and PC2 distinguish between insulin-producing pancreatic islet beta cells and non-beta cells. AB - PC1 (PC3) and PC2, members of the mammalian family of proprotein convertases homologous to the yeast Kex2 gene product, are both expressed in pancreatic islets of Langerhans. Recent studies have suggested that PC1 and PC2 are responsible for the conversion of proinsulin to insulin and connecting peptide (C peptide) in the islet beta cells. However, the insulin-secreting beta cells are not the only cells present in these complex micro-organs, prompting us to evaluate the expression of PC1 and PC2 in islet beta and non-beta cells. Rat islet cells were sorted by autofluorescence-activated flow cytometry to separate beta cells from non-beta cells, and conversion endoprotease levels were analysed by Western blotting. The immunolabel ratio of PC1/PC2 in beta cells was 2.6. Non beta cells displayed much lower levels of PC1 than beta cells, but twice as much PC2 (PC1/PC2 = 0.05). Post-translational modification of the convertases themselves was found to differ between the cell types. In particular, a 75 kDa precursor form of PC2 (pro-PC2) was found to accumulate in beta cells, whereas only the fully processed 67 kDa form was detected in the non-beta cells. Finally, the quantification of PC1 and PC2 and their precursor forms in transformed cells (insulin-producing beta-TC and glucagon-producing alpha-TC) showed that transformation appeared to be accompanied by unusually high levels of the precursors. PMID- 8198552 TI - Increase in retinyl palmitate concentration in eyes and livers and the concentration of interphotoreceptor retinoid-binding protein in eyes of vitiligo mutant mice. AB - Retinyl esters play an important role in the visual cycle because they are involved in regeneration of 11-cis-retinal for use in rhodopsin formation. In the present study, retinyl ester concentrations were significantly elevated in eyes and livers of mice homozygous for the vitiligo mutation (mivit/mivit). Vitiligo mice demonstrate a slowly progressing retinal degeneration characterized by gradual loss of photoreceptor cells and rhodopsin as well as uneven pigmentation of the retinal pigment epithelium (RPE). Analysis of retinoids by h.p.l.c. indicated that the retinyl palmitate level was increased fivefold in eyes of affected mice at 10 weeks postnatally and was threefold higher at 22 weeks of age. Accumulation of retinyl palmitate occurred in the RPE rather than the neural retina. Furthermore, the concentration of all-trans-retinol was elevated in the RPE of vitiligo mice. Levels of interphotoreceptor retinoid binding protein (IRBP) were increased in vitiligo mice between ages 4 and 14 weeks, but returned to normal by 16 weeks. Increased IRBP levels were not due to increased protein synthesis because IRBP mRNA levels did not differ significantly between control and affected animals. To examine possible systemic involvement in vitiligo mice, retinoids were evaluated in liver and plasma. Mean hepatic total vitamin A levels in affected mice were approximately 1.7 times higher than controls. Analysis of esterified and non-esterified retinoids in liver showed that the concentration of retinyl palmitate was elevated. Plasma retinol levels were normal. This study provides the first evidence of altered systemic retinoid metabolism in vitiligo mice, which occurs, significantly, under normal dietary conditions. PMID- 8198553 TI - A new alternative transcript encodes a 60 kDa truncated form of integrin beta 3. AB - A cDNA for integrin beta 3 isolated from a human erythroleukaemia (HEL) cell library contained a 340 bp insert at position 1281. This mRNA, termed beta 3c, results from the use of a cryptic AG donor splice site in intron 8 of the beta 3 gene, and is different from a previously described alternative beta 3 mRNA. The predicted open reading frame of beta 3C stops at a TAG stop codon 69 bp downstream from position 1281. It starts with the signal peptide and the 404 N terminal extracellular residues of beta 3, encompassing the ligand binding sites, followed by 23 C-terminal intron-derived residues, corresponding to a truncated form of beta 3 lacking the cysteine-rich, transmembrane and cytoplasmic domains. Expression of beta 3C mRNA was demonstrated in human platelets, megakaryocytes, endothelial cells and HEL cells by reverse transcriptase/PCR. The beta 3C transcript was also demonstrated in the mouse, suggesting its conservation through evolution. Finally, a 60 kDa polypeptide corresponding to the beta 3C alternative transcript was demonstrated in platelets by Western blotting using a polyclonal antibody raised against a synthetic peptide designed from the beta 3C intronic sequence. Taken together, these results suggest a biological role for beta 3C, the first alternative transcript showing an altered extracellular domain of a beta integrin. PMID- 8198554 TI - Investigation of the cofactor-binding site of Zymomonas mobilis pyruvate decarboxylase by site-directed mutagenesis. AB - Several enzymes require thiamin diphosphate (ThDP) as an essential cofactor, and we have used one of these, pyruvate decarboxylase (PDC; EC 4.1.1.1) from Zymomonas mobilis, as a model for this group of enzymes. It is well suited for this purpose because of its stability, ease of purification and its simple kinetic properties. A sequence motif of approx. 30 residues, beginning with a glycine-aspartate-glycine (-GDG-) triplet and ending with a double asparagine ( NN-) sequence, has been identified in many of these enzymes [Hawkins, Borges and Perham (1989) FEBS Lett. 255, 77-82]. Other residues within this putative ThDP binding motif are conserved, but to a lesser extent, including a glutamate and a proline residue. The role of the elements of this motif has been clarified by the determination of the three-dimensional structure of three of these enzymes [Muller, Lindqvist, Furey, Schulz, Jordan and Schneider (1993) Structure 1, 95 103]. Four of the residues within this motif were modified by site-directed mutagenesis of the cloned PDC gene to evaluate their role in cofactor binding. The mutant proteins were expressed in Escherichia coli and found to purify normally, indicating that the tertiary structure of these enzymes had not been grossly perturbed by the amino acid substitutions. We have shown previously [Diefenbach, Candy, Mattick and Duggleby (1992) FEBS Lett. 296, 95-98] that changing the aspartate in the -GDG- sequence to glycine, threonine or asparagine yields an inactive enzyme that is unable to bind ThDP, therefore verifying the role of the ThDP-binding motif. Here we demonstrate that substitution with glutamate yields an active enzyme with a greatly reduced affinity for both ThDP and Mg2+, but with normal kinetics for pyruvate. Unlike the wild-type tetrameric enzyme, this mutant protein usually exists as a dimer. Replacement of the second asparagine of the -NN- sequence by glutamine also yields an inactive enzyme which is unable to bind ThDP, whereas replacement with an aspartate residue results in an active enzyme with a reduced affinity for ThDP but which displays normal kinetics for both Mg2+ and pyruvate. Replacing the conserved glutamate with aspartate did not alter the properties of the enzyme, while the conserved proline, thought to be required for structural reasons, could be substituted with glycine or alanine without inactivating the enzyme, but these changes did reduce its stability. PMID- 8198555 TI - Structural requirements for the utilization of ascorbate analogues in the prolyl 4-hydroxylase reaction. AB - The ability of structural analogues of ascorbate to serve as substitutes for this reducing agent in the prolyl 4-hydroxylase reaction was studied. In experiments using the purified enzyme, variations of the compounds' side chain were compatible with co-substrate activity. The presence of very large hydrophobic substituents or a positively charged group caused an increase in the observed Km values. A negative charge and smaller modifications did not change the affinity to the enzyme when compared with L-ascorbate. 6-Bromo-6-deoxy-L-ascorbate had a lower Km than the physiological reductant. Substitution at the -OH group in ring position 3 prevented binding to the enzyme. The same pattern of activity was observed when the full and uncoupled prolyl 4-hydroxylase reactions were studied. The Vmax. values with all compounds were similar. The reaction of microsomal prolyl 4-hydroxylase was supported by D-isoascorbate, O6-tosyl-L-ascorbate and 5 deoxy-L-ascorbate, giving the same dose-response behaviour as L-ascorbate itself. Again, 6-bromo-6-deoxy-L-ascorbate gave a lower Km and a similar Vmax. value. L Ascorbic acid 6-carboxylate produced substrate inhibition at concentrations above 0.3 mM. The Km and Vmax. values calculated from concentrations up to 0.2 mM were similar to those of L-ascorbate. The enzyme activity observed with 6-amino-6 deoxy-L-ascorbate was very low in the microsomal hydroxylation system. The calculated Vmax. value was lower than that of L-ascorbate, suggesting a restriction of the access of this compound to the enzyme. PMID- 8198556 TI - Inhibition of inositol trisphosphate-induced calcium release by caffeine is prevented by ATP. AB - We have investigated the effect of various methylxanthines on the basal and InsP3 stimulated unidirectional 45Ca2+ efflux from permeabilized A7r5 cells under different experimental conditions. We report that caffeine and theophylline inhibit the InsP3-induced Ca2+ release, whereas the basal Ca2+ leak remained largely unaffected. The effect on InsP3-induced Ca2+ release was specific, since isocaffeine was not effective. The inhibition occurred similarly in the absence or presence of extravesicular Ca2+ and was not associated with a decrease in the [3H]InsP3 binding to the receptor. ATP and MgATP (5 mM) prevented the inhibition, suggesting that caffeine may interact with an ATP-binding site on the InsP3 receptor or some associated protein. PMID- 8198557 TI - Cloning and expression in Escherichia coli of a dog thyroid cDNA encoding a novel inositol 1,4,5-trisphosphate 5-phosphatase. AB - In brain and many other tissues, type I inositol 1,4,5-trisphosphate (InsP3) 5 phosphatase is the major isoenzyme hydrolysing the calcium-mobilizing second messenger InsP3. This protein has been purified to apparent homogeneity from a crude soluble fraction of bovine brain, yielding a single major protein band with a molecular mass of 43 kDa after SDS/PAGE. This material was used to determine internal microsequences. A partial DNA sequence has been amplified by PCR by using degenerate primers deduced from two protein sequences (FKAKKYKKV and DENYKSQE). A cDNA clone (BVCT) was isolated by screening a dog thyroid cDNA library. The encoded protein of 412 amino acids has a calculated molecular mass of 47,681 Da. Peptide sequences generated from the bovine brain enzyme were found to be 96% conserved compared with the dog thyroid protein. When clone BVCT was expressed in Escherichia coli, the recombinant protein was shown to hydrolyse both InsP3 and inositol 1,3,4,5-tetrakisphosphate, with apparent Km values of 28 and 3 microM respectively. Enzyme activity was inhibited by EDTA and 2,3 bisphosphoglycerate, both inhibitors of native InsP3 5-phosphatase, but not by EGTA and LiCl, as previously shown for the bovine brain enzyme. Our data show the cloning of type I InsP3 5-phosphatase which, interestingly, does not share any significant sequence identity with the previously cloned type III isoenzyme. PMID- 8198558 TI - Inactivation of yeast hexokinase by Cibacron Blue 3G-A: spectral, kinetic and structural investigations. AB - Yeast hexokinase, a homodimer (100 kDa), is an important enzyme in the glycolytic pathway. Although Cibacron Blue 3G-A (Reactive Blue 2) has been previously shown to inactivate yeast hexokinase, no comprehensive study exists concerning the nature of interaction(s) between hexokinase and the blue dye. A comparison of the computer-generated three-dimensional (3D) representations showed considerable overlap of the purine ring of ATP, a nucleotide substrate of hexokinase, with the hydrophobic anthraquinone moiety of the blue dye. The visible spectrum of the blue dye showed a characteristic absorption band centred at 628 nm. The visible difference spectrum of increasing concentration of the dye and the same concentrations of the dye plus a fixed concentration of hexokinase exhibited a maximum, a minimum and an isobestic point at 683, 585, and 655 nm respectively. The visible difference spectrum of the blue dye and the dye in 50% ethylene glycol showed a maximum and a minimum at 660 and 570 nm respectively. The visible difference spectrum of the blue dye in the presence of the dye and hexokinase modified at the active site by pyridoxal phosphate, iodoacetamide and o phthalaldehyde was devoid of bands characteristic of the hexokinase-blue dye complex. Size-exclusion-chromatographic studies in the absence or presence of guanidinium chloride showed that the enzyme inactivated by the blue dye was co eluted with the unmodified enzyme. The dialysis residue obtained after extensive dialysis of the gel-filtered complex, against a buffer of high ionic strength, showed an absorption maximum at 655 nm characteristic of the dye-enzyme complex. Inactivation data when analysed by 'Kitz-Wilson'-type kinetics for an irreversible inhibitor, yielded values of 0.05 min-1 and 92 microM for maximum rate of inactivation (k3) and dissociation constant (Kd) for the enzyme-dye complex respectively. Sugar and nucleotide substrates protected hexokinase against inactivation by the blue dye. About 2 mol of the blue dye bound per mol of hexokinase after complete inactivation. The inactivated enzyme could not be re activated in the presence of 1 M NaCl. These results suggest that Cibacron Blue 3G-A inactivated hexokinase by an irreversible adduct formation at or near the active-site. Spectral and kinetic studies coupled with an analysis of the 3D representations of model compounds corresponding to the substructures of the blue dye suggest that 1-amino-4-(N-phenylamino)anthraquinone-2-sulphonic acid part of the blue dye may represent the minimum structure of Cibacron Blue 3G-A necessary to bind hexokinase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8198559 TI - Selective inhibition of adenylate cyclase in bovine cortex by quinones: a novel cellular substrate for quinone cytotoxicity. AB - Quinones are widely distributed substances of often potential toxicological significance. On the other hand, cyclic AMP is known to promote a cell-survival response and to retard apoptosis [Berridge, Tan and Hilton (1993) Exp. Hematol. 21, 269-276]. Therefore the effects of quinones on adenylate cyclase were tested. Adenylate cyclase is rapidly inhibited by quinones, with IC50 values of 40-45 microM for p-benzoquinone (BQ) or 200 microM for dichlorophenol-indophenol (DCIP), with 2-substituted quinones being inactive. Membrane solubilization decreases the IC50 values for BQ and DCIP to 18 microM and 40 microM respectively. The inhibition is not affected by GTP, GDP or analogues, or by cholera and pertussis toxins; therefore it is not mediated by a G-protein or the activation of a defined receptor. Further, the inhibition stoichiometrically competes with forskolin activation of adenylate cyclase, equimolar concentrations of quinone and forskolin restoring the enzyme activity to its basal value. Reduction of BQ with sodium dithionite stoichiometrically prevents the inhibition of adenylate cyclase; in turn, oxidation of hydroquinone with ferricyanide fully restores it, indicating that the oxidized state of the quinone is required for inhibition. In addition, BQ is cytotoxic in vivo on HepG2, a human hepatocellular carcinoma cell line, but the effect can be prevented with forskolin. In plasma membranes, BQ tightly binds only one major and two minor proteins; these BQ binding proteins were purified by means of labelling with [14C]BQ followed by PAGE under native conditions. Together these observations indicate that the action of quinone can be traced to targeting a limited number of proteins at the plasma membrane in a highly selective way and to affecting key enzymes such as adenylate cyclase. PMID- 8198560 TI - The effect of polyamine depletion on the cytotoxic response to PUVA, gamma rays and UVC in V79 cells in vitro. AB - Difluoromethylornithine (DFMO) depletes cells of polyamines, sensitizing cells against the action of antineoplastic drugs and altering ability to repair radiation-induced DNA strand breaks. Others have hypothesized that the mechanism by which polyamine depletion sensitizes cells is through inhibition of DNA strand break repair or through altering the spectrum of initial DNA damage. We have compared the effect of polyamine depletion on cytotoxic effects in V79 cells for three agents that damage DNA: PUVA (8-methoxypsoralen and ultraviolet light, 365 nm), gamma-rays and UVC (ultraviolet light, 254 nm) in polyamine depleted V79 cells. DFMO pretreatment sensitizes cells to PUVA and gamma-ray toxicity but not to UVC. Unlike UVC photoinduction of DNA lesions, PUVA- and gamma-ray-induced DNA damage is modulated by chromatin structure. Our results suggest that polyamine depletion sensitizes cells to the action of PUVA and gamma-rays by mechanisms disparate from those for UVC, suggesting that the level or type of initial damage, rather than DNA repair, per se, may be the more important determinant of enhanced cytotoxicity. PMID- 8198561 TI - The primary structure of rat ribosomal protein L13. AB - The amino acid sequence of the rat 60S ribosomal subunit protein L13 was deduced from the sequence of nucleotides in two recombinant cDNAs. Ribosomal protein L13 has 210 amino acids, the NH2-terminal methionine is removed after translation of the mRNA and has a molecular weight of 24,094. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 8 to 10 copies of the L13 gene. The mRNA for the protein is about 870 nucleotides in length. Rat L13 is related to ribosomal proteins from other eukaryotes. PMID- 8198562 TI - The primary structure of rat ribosomal protein L15. AB - The amino acid sequence of the rat 60S ribosomal subunit protein L15 was deduced from the sequence of nucleotides in two recombinant cDNAs. Ribosomal protein L15 has 203 amino acids, the NH2-terminal methionine is removed after translation of the mRNA, and has a molecular weight of 24,000. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 13 to 15 copies of the L15 gene. The mRNA for the protein is about 850 nucleotides in length. Rat L15 is related to ribosomal proteins from other eukaryotes. Rat L15 has the hexapeptide, TYKFFE, that also occurs in the amyloidogenic glycoprotein A4 which is associated with Alzheimer's disease and Down's Syndrome. PMID- 8198563 TI - The disbalance of alpha- and beta-globins in anemic Belgrade rat red blood cells. AB - The Belgrade Laboratory (b/b) rat has an autosomal mutation which in homozygous state induces severe anemia. This study was based on solubilization of total rat globin chains and their separation into alpha- and beta-globins using a 20% SDS polyacrylamide gel. These analyses demonstrated that the disbalance of alpha/beta globins in b/b red blood cells (RBC) is due to decreased level of alpha-globins. Iron-dextran administration corrected the level and globin ratio in b/b RBC thus confirming that the iron deficiency is the primary defect in b/b rats. PMID- 8198565 TI - Involvement of histidine residues in the catalytic mechanism of hydrogenases. AB - In spite of their structural and amino acid sequence differences, Fe-only and Ni containing hydrogenases achieved the same catalytic reactions. A chemical modification of histidine residues using a highly specific reagent (pentaammineruthenium II) has been carried out on Desulfovibrio vulgaris Hildenborough Fe-hydrogenase and Desulfovibrio desulfuricans Norway Ni-Fe-Se hydrogenase. The preliminary results obtained suggest the existence of a general mechanism involving histidine residues in the two groups of hydrogenases. These residues may be part of the histidine-containing motive shown to be present in both Fe- and Ni-Fe-hydrogenase sequences by Hydrophobic Cluster Analysis. This analysis also allows us to suggest a functional role for the small subunit of Desulfovibrio vulgaris Hildenborough Fe-hydrogenase. PMID- 8198564 TI - Glutathione S-transferase-sspA fusion binds to E. coli RNA polymerase and complements delta sspA mutation allowing phage P1 replication. AB - Bacteriophage P1 is unable to form plaques on E. coli hosts lacking a functional sspA gene. However, sspA mutants can be infected by P1, resulting in the synthesis of P1 early gene products and accumulation of P1 DNA, but without P1 late gene product formation or host lysis. Overexpression of the stringent starvation protein (SspA) as a glutathione-S-transferase fusion results in complementation of the sspA mutation and production of viable viral particles as in sspA+ strains. This suggests that the GST-SspA protein functions in vivo in a similar manner as native SspA with respect to P1 replication. Here, evidence is presented that shows that SspA binds to RNA-polymerase. This supports the notion that SspA is involved in P1 replication since it is known that P1 requires host RNA-polymerase activity to replicate and this suggests a mechanism by which P1 redirects E. coli RNA-polymerase specificity from P1 early to P1 late genes. PMID- 8198566 TI - Regulation of protein kinase C in NG108-15 cell differentiation. AB - The involvement of PKC in NG108-15 cell differentiation was investigated. Differentiation with dBcAMP was associated with a decrease in total cellular phorbol ester binding. The histone-directed PKC activity was decreased in the soluble fraction. Northern and Western blotting revealed the presence of only PKC alpha but not PKC beta and PKC gamma among the calcium-dependent isoforms. Differentiation induced a decrease of cytosolic PKC alpha immunoreactivity, with no changes of mRNA content or appearance of PKC beta and PKC gamma isoforms. The low levels of PKC alpha in the soluble fraction suggest that the mRNA for this species is less efficiently translated in differentiated NG108-15 cells. The data suggest that down-regulation of PKC alpha protein and kinase activity are associated with induction of neuronal morphology in NG108-15 cells. PMID- 8198567 TI - A novel 34 kDa glutathione-binding protein in mature rat ovary. AB - A novel protein that binds to a glutathione-Sepharose affinity column has been detected in mature, but not immature, rat ovary. This protein could be resolved from all identifiable components when the affinity-purified material, containing primarily glutathione transferases, was analyzed on reversed phase-HPLC. The unidentified protein migrated with an apparent molecular weight of 34 kDa on SDS PAGE. After purification by affinity chromatography and subsequent preparative electrophoresis, the protein was subjected to N-terminal amino acid sequence analysis. The sequence obtained demonstrated a high degree of homology with an internal amino acid sequence in human carbonyl reductase (EC 1.1.1.184). PMID- 8198568 TI - The cleavage of phosphoenolpyruvate by vanadate. AB - Vanadate rapidly promotes the cleavage of phosphoenolpyruvate with phosphate liberation. This was not observed when ATP, glucose-6-phosphate and acetyl phosphate were incubated with vanadate. 51V NMR spectra shows that phosphoenolpyruvate and acetyl phosphate broadened and shifted upfield the monomeric vanadate signal at -561 ppm, indicative of vanadate/phosphate interactions. Comparatively, smaller changes were detected when glucose-6 phosphate was added to the vanadate solution. The shift behavior was not observed in the presence of ATP, ADP or pyruvate. PMID- 8198569 TI - Salmonella typhimurium activates human immunodeficiency virus type 1 in chronically infected promonocytic cells by inducing tumor necrosis factor-alpha production. AB - The effect of phagocytosis of Salmonella typhimurium on human immunodeficiency virus type 1 (HIV-1) production was investigated using a chronically infected promonocytic cell line (U1) that contains HIV-1 provirus but produces little or no HIV-1. The phagocytosis of virulent S. typhimurium by U1 cells resulted in an increased HIV-1 expression as evidenced by significant increase in HIV-1 p24 antigen in culture supernatants. In contrast, heat-killed S. typhimurium failed to induce HIV-1 expression. In addition, phagocytosis of virulent S. typhimurium and not of heat-killed S. typhimurium resulted in a significant induction of tumor necrosis factor-alpha (TNF-alpha) mRNA expression and secretion of TNF alpha by U1 cells. Furthermore, anti-TNF-alpha monoclonal antibody inhibited S. typhimurium-induced HIV-1 p24 antigen production. These data suggest that S. typhimurium induces HIV-1 expression in U1 cells via production of TNF-alpha. PMID- 8198570 TI - Expression of soluble active human beta 1,4 galactosyltransferase in Saccharomyces cerevisiae. AB - Sequences coding for the cytoplasmic and transmembrane domains were removed from the cDNA of the human Golgi resident membrane protein beta 1,4 galactosyltransferase (gal-T). The remaining sequences coding for the stem and catalytical domains of this glycosyltransferase were fused to sequences coding for the yeast invertase signal sequence. The hybrid was inserted together with a constitutive yeast promoter and a terminator into a E. coli/yeast shuttle vector. Saccharomyces cerevisiae strain BT150 transformed with this new expression vector expressed enzymically active soluble enzyme, whereas no activity was detectable in mock-transformed yeasts. The enzyme product was identified by HPLC analysis and shown to correspond to the expected product N-acetyllactosamine. PMID- 8198571 TI - Inhibitors of sterol synthesis: 3 beta-hydroxy-25,26,26,26,27,27,27- heptafluoro 5 alpha-cholestan-15-one, an analog of a potent hypocholesterolemic agent in which its major metabolism is blocked. AB - The chemical synthesis of 3 beta-hydroxy-25,26,26,26,27,27,27-heptafluoro- 5 alpha-cholestan-15-one (IV) has been pursued to provide an analog of the potent hypocholesterolemic agent 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one (I) in which its major metabolism is blocked. Reduction of 3 beta-acetoxy-5 alpha-chola 8(14),23-dien-15-one with lithium in liquid ammonia gave 3 beta-hydroxy-5 alpha chol-23-en-15-one (VI). Addition of (CF3)2CFI to VI in the presence of triethylborane gave 3 beta-hydroxy-23R-iodo-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholestan- 15-one, which was reduced to IV with tributyltin hydride. IV was found to be highly active in lowering the levels of HMG-CoA reductase activity in CHO-K1 cells, in lowering acyl coenzyme A:cholesterol acyltransferase activity in jejunal microsomes, and in lowering serum cholesterol levels in rats. PMID- 8198572 TI - Differential expression of members of the N-formylpeptide receptor gene cluster in human phagocytes. AB - The human genes for two N-formylpeptide phagocyte chemoattractant receptors (gene symbols FPR1 and FPRL1) cross-hybridize with each other and with FPRL2, a human gene of unknown expression and function. The FPR1 product is approximately 1000 fold more sensitive than the FPRL1 product to N-formylpeptides. We now report cloning of the first cDNA for FPRL2 and the first description of the RNA distribution in normal human phagocytes for all three genes. FPR1 and FPRL1 are expressed in neutrophils and monocytes. In contrast, FPRL2 RNA is detectable in monocytes but not in neutrophils, and its product could not be activated by N formylpeptides. Thus, the regulation of FPRL2 gene expression in vivo differs from FPR1 and FPRL1. PMID- 8198573 TI - Anti-beta 2 subunit antisense oligonucleotides modulate the surface expression of the alpha 1 subunit of N-type omega-CTX sensitive Ca2+ channels in IMR 32 human neuroblastoma cells. AB - High voltage activated Ca2+ channels are heteropolymeric complexes in which the alpha 1 subunit forms the channel, while the alpha 2-delta and beta subunits are important for the assembly and regulation of the biophysical properties of the channel. We have tested the role of the beta 2 subunit on the expression and electrophysiological properties of the omega-conotoxin GVIA-sensitive Ca2+ channel expressed in the IMR 32 human neuroblastoma cell line. Anti-beta 2 subunit antisense oligonucleotides supplied to the cells in culture induced a time-dependent increase in the number of [125I]-omega-conotoxin binding sites on the cell surface, which was not paralleled by an increase in current amplitude. We suggest that a reduction in the expression of beta 2 stimulates the transport to the plasma membrane of non-functioning Ca2+ channels and, in particular, of the alpha 1 omega-conotoxin binding subunit. PMID- 8198574 TI - Identification of transmembrane domains of the red cell calcium pump with a new photoactivatable phospholipidic probe. AB - The membrane-associated regions of the human erythrocyte Ca2+ pump were investigated by hydrophobic photolabeling. Purified Ca2+ pump was reconstituted in asolectin vesicles loaded with [3H]DIPETPD, a photochemical probe designed to label deeply into the hydrophobic core of the lipid bilayer (Delfino et al. J. Am. Chem. Soc. 115, 3458-3474, 1993). After photolysis and SDS-PAGE analysis, a significant light-dependent labeling of the Ca2+ pump was found. Controlled proteolysis of the photoadduct with trypsin or protease V8 followed by SDS-PAGE and immunoblotting yielded individual labeled fragments. The labeling pattern indicated the existence of three sequential clusters of transmembrane regions, consistent with the current model for the topography of this enzyme. PMID- 8198575 TI - Cloning and sequencing of the equine testicular follitropin receptor. AB - To investigate the possibility that specific structural determinants within the equine follitropin receptor (eFSHR) are critical to the enhanced specificity of this receptor compared to other FSHRs, we used the RACE-PCR technique to clone the eFSHR from equine testis. Sequence analysis revealed that the eFSHR is highly homologous to other mammal FSHRs, but it presents 10 unique amino acid residue replacements in the extracellular domain. Furthermore, a potential N glycosylation site was detected at a position not encountered in other receptors. Northern blot analysis identified three transcripts of 4.2 kb, 2.3 kb and 1.0 kb in horse testis. PMID- 8198576 TI - Evidence for a site-specific endonuclease in yeast mitochondria which recognizes the sequence 5'GCCGGC. AB - We have discovered a mitochondrial, site-specific DNase in Saccharomyces cerevisiae with properties like that of a Type II restriction endonuclease. The enzyme, termed SceIII, cleaves the palindromic sequence 5'GCCGGC, to give 3' ends recessed by 4 bases. SceIII is the first restriction-like endonuclease to be described in yeast mitochondria. PMID- 8198577 TI - Binding of IFN gamma and its C-terminal peptide to a cytoplasmic domain of its receptor that is essential for function. AB - We have previously shown that murine interferon gamma (IFN gamma) binds to a soluble form of its receptor via both the N-terminus and C-terminus. The IFN gamma N-terminus binds extracellular receptor residues 95-120. Here we report that the C-terminus of IFN gamma binds to the membrane proximal region of the cytoplasmic domain of the receptor, residues 253-287. Peptide binding to fixed/permeabilized cells is specifically blocked by anti-(253-287) antibodies. These data suggest a novel mechanism by which IFN gamma binds to its receptor, involving both the extracellular and the intracellular receptor domains. Such a mechanism could have broader implications for the activation of signal transduction pathways by both IFN gamma and other cytokines whose receptors are members of the cytokine receptor superfamily. PMID- 8198578 TI - Identification of a new class of ETA selective endothelin antagonists by pharmacophore directed screening. AB - Novel endothelin antagonists were identified through a "pharmacophore directed screening" strategy. The sulfanilamide antibacterial agent sulfisoxazole was found to be a good endothelin receptor antagonist (IC50's of 0.60 microM and 22 microM for the ETA and ETB receptors, respectively). The structurally similar sulfamethoxazole was found to be a weaker antagonist (IC50 for ETA 16 microM and for ETB 230 microM). These compounds represent a new class of low molecular weight and ETA-selective non-peptide endothelin antagonists. PMID- 8198579 TI - The role of glutathione in the toxicity of a novel cyanobacterial alkaloid cylindrospermopsin in cultured rat hepatocytes. AB - Cylindrospermopsin (CY) is a newly isolated alkaloid produced by the cyanobacterium Cylindrospermopsis raciborskii, which has been linked to an outbreak of hepatoenteritis in man. The current work examined the suitability of primary cultures of rat hepatocytes as an in vitro model for studying the cytotoxicity of CY. We found that CY (3.3-5.0 microM) caused significant cell death (40-67% of cells by LDH release) in cultured hepatocytes after 18 hr incubation. While investigating possible mechanisms for CY toxicity, we found that lower, nontoxic doses of CY (1.6-2.5 microM) decreased cell glutathione (GSH) to about 50% of control. For toxic doses (5 microM), the loss of GSH preceded the onset of toxicity by six hr. Lowering cell GSH predisposed cells to CY toxicity. In conclusion, cultured hepatocytes are a suitable model for studies of CY cytotoxicity and GSH is involved in the detoxification of CY. PMID- 8198580 TI - Release of TEA blockade of maxi-K+ channels by isoproterenol. AB - The outward K+ current induced by step depolarization of freshly dispersed myocytes of guinea-pig taenia coli decreased about 80% upon treatment with 3 mM tetraethylammonium chloride (TEA). Isoproterenol (ISO, 2-5 microM) restored it to a large extent. This restoration did not occur in the presence of propranolol (2 microM). In single-channel recordings from cell-attached patches, the activity of maxi-K+ channel is dominant. When 3 mM TEA is incorporated in the pipette solution, the dominant channel-openings observed had much smaller unitary conductance. On the addition of ISO (2 microM) to the bath solution, but not to the pipette solution, K(+)-channel openings with unitary conductance similar to that without TEA treatment appeared. Cyclic AMP incorporated into the cytoplasm through the pipette was ineffective. These results indicate that ISO release TEA decrease of maxi-K+ channel conductance through some intracellular second messenger system other than adenylyl cyclase-protein kinase A system. PMID- 8198581 TI - Use of single-cysteine mutants to probe the location of the disulfide bond in LamB protein from Escherichia coli. AB - The two cysteine residues of the LamB protein of Escherichia coli outer membrane have been shown to form an intrasubunit disulfide whose location differs greatly in the two current topology models of the LamB protein. This study probes the location of the disulfide by examining conditions for intersubunit disulfide formation in single-cysteine mutants of LamB protein. Formation of an intersubunit bond in the purified mutant proteins, which resulted in a disulfide linked dimer, only occurred after heat treatment, suggesting the disulfide is not exposed on the surface in the native protein. PMID- 8198582 TI - Functional expression or recombinant human luteinizing hormone/human choriogonadotropin receptor. AB - The functional capacity of the recombinant human LH/hCG receptor was tested on the basis of gonadotropin stimulation of cAMP production by stable transfections of Chinese hamster ovary (CHO) cells. A CHO cell line expressed with the hLH/hCG receptor cDNA covering the entire amino acid coding region revealed the presence of LH/hCG binding site (Kd: 1.45 x 10(-10)M) on the plasma membrane. Treatment of transfected cells(CHO-LH/hCGR) with hCG induced dose-dependent increases in intracellular cAMP production, indicating that the expressed human LH/hCG receptor functionally couples with endogenous adenylyl cyclase. Although hCG induced dose-dependent increases in cAMP production, rat and bovine LH and human FSH did not alter cAMP levels compared to control values. Northern blot analysis with a cRNA probe derived from human LH/hCG receptor cDNA indicated the presence of three LH/hCG receptor mRNA transcripts(5.4, 3.6 and 2.4 kilobases) in RNA prepared from human ovary. Preincubation of CHO-LH/hCGR cells with hCG for 16h decreased the subsequent cAMP production caused by a 30min pulse of hCG stimulation. These results indicate that desensitization of the adenylyl cyclase response to hCG stimulation occurs in CHO-LH/hCGR cells. Therefore, this cell line provides a tool with which to pursue detailed studies on the molecular basis of LH/hCG induced desensitization. PMID- 8198583 TI - 13-Hydroxyoctadecadienoic acid reverses epidermal hyperproliferation via selective inhibition of protein kinase C-beta activity. AB - 13-Hydroxyoctadecadienoic acid (13-HODE) is a major lipoxygenase metabolite of linoleic acid in epidermis. Employing a docosahexaenoic acid (22:6n-3) induced model of hyperproliferative guinea pig epidermis, we demonstrated reversal of hyperproliferation by topical 13-HODE. To delineate a possible mechanism for 13 HODE effect, we demonstrated that topical 13-HODE was incorporated into 13-HODE containing diacylglycerol (13HODE-DAG). This novel substituted-DAG which was markedly depleted in the hyperproliferative skin paralleled the increased activities of PKC-alpha and beta. Replenishment of the hyperproliferative epidermis with topical 13-HODE resulted in the accumulation of tissue 13HODE-DAG and the selective suppression of PKC-beta activity. These data taken together suggest that the generation of putative 13-HODE-DAG and the selective suppression of PKC-beta isozyme activity may play a role in modulating epidermal hyperproliferation. PMID- 8198584 TI - Selective induction of apoptosis in myeloid leukemic cell lines by monoacetone glucose-3 butyrate. AB - Butyric acid is a potent cell growth inhibitor and differentiation inducer. Our previous studies have shown that MAG=3but, a monosaccharide ester of butyric acid, used at 1 mM, induces apoptosis in the HL-60 cell line. We report here that this drug can also induce apoptosis in the U-937 leukemic cell lines whereas the myeloblastic KG1 and the NB4 promyelocytic leukemic cell lines were refractory to induction of apoptosis. In order to determine what can trigger cells to undergo apoptosis, cell cycle analysis, induction of differentiation and p53, c-myc and Bcl-2 expression was studied. Apoptosis was correlated to an arrest of cell growth in the G1 phase of the cell cycle and to an induction of differentiation through the monocytic pathway in HL-60 and U-937 cells. Time course studies demonstrated DNA fragmentation after few hours incubation with the drug, while morphological signs appeared later (days 2 or 3). Northern blot analysis and flow cytometric studies have shown that cell death induced by MAG=3but was not associated to an overexpression of c-myc and p53. However, in the HL-60 cells, BCL-2 protein expression was decreased after MAG=3but treatment, corroborating the apoptosis observed. PMID- 8198585 TI - Plant nitrate reductase gene fragments enhance nitrite production in activated murine macrophage cell lines. AB - Nitrate reductase (NR) gene fragments (1.1 kb and 800 bp) from the barley plant were incorporated into pSV2neo and transfected by electroporation into a variety of cell lines of different functionality. Only transfected murine macrophage cell lines demonstrated appreciably enhanced NO2- production (i.e., NR activity) both in the presence and absence of exogenous nitrate (NO3-). Addition of NO3- caused the greatest increase in NO2- production when macrophages were primed with interferon-gamma (INF-gamma) and lipopolysaccharide (LPS). Transfection of RAW 264.7 murine macrophages led to isolation of several novel neomycin-resistant subpopulations designated NR10(1), NR10(2) (both containing the 1.1 kb NR fragment) and NR800(5) (containing the 800 bp NR fragment). Similarly transfected nonleukocytic and leukocytic stem cell lines showed no significant NO2- production. Outside of the macrophage cell lines, only the murine T cell line EL 4 showed evidence of mild nitrite production enhancement. The mechanism of enhanced NO2- formation in NR transfected murine macrophages is unknown. However, study of these novel cells may lead to greater understanding of the expression of a plant NR in mammalian cells and highly controlled production of a cytotoxic molecule (NO2-) in macrophages. PMID- 8198586 TI - Competitive inhibition of HIV-1 protease by warfarin derivatives. AB - The oral anticoagulant warfarin (4-hydroxy-3-(3-oxo-1-phenylbutyl)- benzopyran-2 one) is a structurally novel low micromolar competitive inhibitor of HIV-1 protease in vitro. It was recently reported that warfarin inhibits HIV-1 infection in U-1 monocytes and viral production in ACH-2 lymphocytes (Bourinbaiar, A.S. et al., (1993) AIDS 7, 129-130). Our results demonstrate that warfarin and a series of structurally related analogs inhibit the viral protease, the most potent analog having an IC50 = 1.9 microM. Kinetic analysis reveals inhibition by warfarin occurs in a competitive manner, with Ki = 3.3 microM. While it is unclear whether the cellular inhibition previously reported is due to inhibition of HIV-1 protease, the warfarin analogs are a novel class of nonpeptide HIV-1 protease inhibitors. PMID- 8198587 TI - Site-directed mutagenesis of the histamine H1-receptor reveals a selective interaction of asparagine207 with subclasses of H1-receptor agonists. AB - In this study we investigated the role of the threonine203 and the asparagine207 residues in the fifth transmembrane domain of the guinea-pig histamine H1 receptor by site-directed mutagenesis to non-functional alanines. Whereas the threonine203 residue is not important for the action of histamine, the asparagine207 residue appears to be involved in the binding of the N tau-nitrogen atom of histamine and its 2-methyl-analogue. For the 2-phenyl-analogue and non imidazole H1-receptor agonists, this residue is, however, not essential for binding. On the basis of this study we conclude that different histamine H1 receptor agonists interact in different ways with the H1-receptor protein. Moreover, we speculate that the interaction with the N pi-nitrogen atom is essential for H1-receptor activation. PMID- 8198588 TI - Isolation of a cDNA for the catalytic subunit of rat liver glucose-6-phosphatase: regulation of gene expression in FAO hepatoma cells by insulin, dexamethasone and cAMP. AB - cDNA clones coding for the catalytic subunit of rat liver glucose-6-phosphatase (EC 3.1.3.9) were isolated from a rat liver cDNA library in lambda gt11 phage. The sequence of the cDNA and the amino acid sequence derived from it were greater than 90% identical to the corresponding sequences for the mouse and human forms of liver glucose-6-phosphatase. Northern blot analysis of RNA from FAO hepatoma cells revealed that dexamethasone induced the glucose-6-phosphatase mRNA while insulin suppressed its expression. When both hormones were added together insulin completely suppressed the effect of glucocorticoid. cAMP addition alone decreased the abundance of glucose-6-phosphatase mRNA. The results demonstrate multihormonal regulation of gene expression of hepatic glucose-6-phosphatase and support a dominant role for insulin. PMID- 8198589 TI - A possible yeast homolog of human active-gene-repairing helicase ERCC6+. AB - We report here the sequencing and identification on the chromosome X of S. cerevisiae of an open reading frame, designated GTA1085, encoding a protein 1085 amino acids in size that displays significant homology to a of helicase subfamily. The highest similarity score is with ERCC6, a human putative helicase involved in the repair of active genes, with 53.3% identity over a stretch of 589 amino acids. This putative protein contains all seven consecutive domains conserved among DNA and RNA helicases. Thus, it apparently constitutes a novel member of this subfamily and might be involved, like ERCC6, in the preferential repair of active genes in yeast. PMID- 8198590 TI - Characterization of recombinant mouse perforin expressed in insect cells using the baculovirus system. AB - Perforin, a potent pore-forming protein, plays an important role in killer lymphocyte-mediated cytolysis. The studies on perforin, although already extensive, have been hampered by the limited amount of perforin naturally available from killer lymphocytes. In the present study, a full-length mouse perforin was expressed in insect cells using recombinant baculovirus. Recombinant perforin appeared to be functional in terms of lysing erythrocytes and nucleated target cells. These results suggest that the recombinant DNA approach developed in the present study may offer a new way for preparing sufficient amounts of engineered perforin for use in the studies aimed at dissecting the functional domains of the perforin molecule. PMID- 8198591 TI - Specificity of vascular endothelial cell growth factor receptor ligand binding domains. AB - Vascular endothelial cell growth factor binds with high affinity to FLT and KDR, two homologous tyrosine kinase receptors expressed on vascular endothelial cells. Placental growth factor, a vascular endothelial cell growth factor homologue, also binds with high affinity to the extracellular domains of FLT but not to the extracellular region of KDR. Vascular endothelial cell growth factor binds competitively with placental growth factor to the extracellular ligand binding domains of FLT, indicating that both ligands probably complex to overlapping or identical regions of this receptor. PMID- 8198592 TI - A 28 kDa-protein with disintegrin-like structure (jararhagin-C) purified from Bothrops jararaca venom inhibits collagen- and ADP-induced platelet aggregation. AB - A 28 kDa-protein with inhibitory activity on collagen- and ADP-induced platelet aggregation was purified from the venom of the snake Bothrops jararaca. Its complete amino acid sequence corresponded to the carboxyl-terminal region consisting of disintegrin-like and cysteine-rich domains of jararhagin, a high molecular weight hemorrhagic metalloprotease. Sequence homology of the protein to other disintegrins and disintegrin-like proteins from various snake venoms is also presented. PMID- 8198593 TI - Enhancement of adenylate cyclase stimulation by prostaglandin E receptor EP3 subtype isoforms with different efficiencies. AB - We recently cloned the mouse prostaglandin (PG) E receptor EP3 subtype that is coupled to adenylate cyclase inhibition through Gi and identified two isoforms of EP3, EP3 alpha and EP3 beta, which are produced through alternative splicing and differ only in the carboxyl-terminal domain. Preincubation of Chinese hamster ovary cells expressing each isoform with PGE2 concentration-dependently enhanced both the basal and forskolin-stimulated cAMP formation, but two orders higher concentrations of PGE2 were required for EP3 beta than EP3 alpha for 50% enhancement of both formations. This enhancement by EP3 isoforms was completely blocked by pertussis toxin treatment, indicating that it is mediated through Gi activation. Thus, the two EP3 isoforms with different carboxyl-terminal tails induce enhancement of adenylate cyclase stimulation with different efficiencies. PMID- 8198594 TI - Fur (ferric uptake regulation) protein interaction with target DNA: comparison of gel retardation, footprinting and electron microscopy analyses. AB - Fur-DNA interactions were analyzed within the regulatory regions of aerobactin and hemolysin operons by a combination of biochemical and ultrastructural methods. Cartography of the Fur binding sites, carried out from electron micrographs, agreed with the data obtained by DNase I footprinting. Visualization of the complexes confirmed the specificity and metal-dependence of Fur binding and demonstrated that the protein polymerizes on its binding sites. Such a polymerization could be involved in the repression process of the bacterial regulator. PMID- 8198595 TI - The heterologous expression and characterization of human prostaglandin G/H synthase-2 (COX-2). AB - The open reading frame of human cyclooxygenase-2 was cloned by pcr amplification of IL-1 beta stimulated human dermal fibroblast cDNA. The coding region was used to construct a recombinant baculovirus which when used to infect Sf9 cells directed the expression of recombinant human cyclooxygenase-2. The heterologously expressed enzyme was characterized and found to display all salient features of cyclooxygenase. Large-scale microsomal preparations of infected cells yielded more than 20 units of enzyme with a specific activity of 240 nmoles prostaglandin product/mg protein. PMID- 8198596 TI - Opposite effects of the overexpression of protein kinase C gamma and delta on the growth properties of human glioma cell line U251 MG. AB - In order to address the question of whether protein kinase C (PKC) is involved in the growth regulation of human glioma cells, we introduced PKC cDNA expression vectors into a human glioma cell line, U-251 MG, and established sets of stable cell clones that overexpress PKC gamma or delta. Cell clones obtained by the transfection of PKC gamma cDNA express 3.6 to 5 times more PKC activity than parental cells that express predominantly endogenous PKC alpha. These PKC gamma overexpressing cell clones show an increased rate of growth in monolayer culture, increased colony-forming efficiency on soft agarose, and increased DNA synthesis in response to epidermal growth factor and basic fibroblast growth factor. Cell clones obtained by transfection with PKC delta cDNA express 2 to 10 times more PKC than that produced endogenously. PKC delta overexpressing cells show a decreased rate of growth and decreased colony-forming efficiency. However, these PKC delta cell clones show no significant changes in responsiveness to the growth factors described above. These results clearly indicate that different PKC family members have distinct regulatory functions in cell growth and that PKC is involved in several aspects of the growth regulation of human glioma cells. PMID- 8198597 TI - Oxidation of low molecular weight chloroalkanes by cytochrome P450CAM. AB - Cytochrome P450CAM from Pseudomonas putida G786 oxidized chlorinated ethanes and 1,2-dichloropropane. The rate of NADH oxidation decreased with decreasing chlorine substitution. The single detectable oxidation products of 1,1,1 trichloroethane and 1,2-dichloropropane were 1,1,1-trichloroethanol and chloroacetone, respectively. Organic product formation was largely uncoupled from NADH oxidation. PMID- 8198598 TI - Cloning and characterization of the human thromboxane synthase gene promoter. AB - A genomic phage clone hybridized to the 5' end of human thromboxane synthase (TS) cDNA was isolated. Sequencing analysis of a 1.7 kb subfragment revealed that it contained the entire 5' untranslated region and 46 bp of the coding sequence of TS cDNA, an upstream canonical TATA box (TATAAA), and several binding sites for transcription factors (AP1, PEA3, PU.1, and GR), indicative of a promoter/first exon region of the TS gene. RNase protection assay mapped the transcription start site of the human TS gene to the nucleotide A 30 bp downstream from the TATA box. The authenticity of the promoter was further confirmed by its ability to direct expression of a CAT reporter gene in transfected HL60 cells. PMID- 8198599 TI - Regulation of ferritin synthesis in macrophages by oxygen and a sulfhydryl reactive agent. AB - Ferritin synthesis is known to be regulated translationally by specific mRNA protein interactions between an iron-responsive element (IRE) localized in the 5' untranslated region of ferritin mRNA and IRE-binding protein (IRE-BP). Binding of IRE-BP to IRE depresses its translation. In the present study, we demonstrated that ferritin synthesis in macrophages is strongly induced under hypoxic conditions by diethylmaleate, a sulfhydryl-reactive agent. The induction by diethylmaleate decreased as the oxygen tension rose. O2- is involved in this oxygen effect, because the induction was prevented when O2(-)-generating agents were present. Actinomycin D did not inhibit the ferritin synthesis induced by diethylmaleate under hypoxi. These results suggest that O2- is involved in post transcriptional regulation of ferritin synthesis. PMID- 8198600 TI - Inverse expression of two laminin binding proteins, 67LR and galectin-3, correlates with the invasive phenotype of trophoblastic tissue. AB - Tumor invasion of host tissues and trophoblastic penetration of the endometrium share common biological features. Both processes involve the invasion of basement membranes, an event that is initiated by adhesion of cancer or trophoblast cells to basement membrane components and particularly to laminin. Adhesion to this latter glycoprotein is mediated through a variety of cell surface receptors. We have previously shown that the 67 kD Laminin Receptor (67LR) and a 31 kD Human Laminin Binding Protein, recently renamed galectin-3, are inversely modulated as the invasive phenotype of cancer cells progresses, with up regulation of the former, and down regulation of the latter, respectively. In this study, we examined the expression of these two proteins in 27 human trophoblastic specimens at different gestational ages using Northern and Western blot techniques. Expression of the 67LR increased from 7 weeks to a maximum at 12 weeks, when invasion is maximal, and then decreased. Expression of galectin-3 was inversely modulated by the gestational age, with a minimum expression at 12 weeks. Our data demonstrate that invasive trophoblast displays the same pattern of laminin binding proteins expression than invasive cancer cells, and further demonstrates that invasion of the extracellular matrix by trophoblast and cancer cells share common molecular mechanisms. PMID- 8198601 TI - Nonnuclear effects of the steroid hormone 1 alpha,25(OH)2-vitamin D3: analogs are able to functionally differentiate between nuclear and membrane receptors. AB - The steroid hormone 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] stimulates biological responses via both genomic mechanisms and nongenomic mechanisms (opening of voltage-gated Ca2+ channels). We report here that the two closed B ring steroid analogs of 1 alpha,25(OH)2D3, 1 alpha,25(OH)2-7-dehydrocholesterol and 1 alpha,25(OH)2-lumisterol3, are able to generate the nongenomic response, transcaltachia, without the ability to compete with the natural metabolite for binding to its nuclear receptor. We propose that the nongenomic membrane associated receptor can accept the ligand in its closed "6-s-cis" conformation whereas the nuclear receptor prefers the extended "6-s-trans" conformer. PMID- 8198602 TI - Evidence for transcapillary transport of reduced glutathione in vascular perfused guinea-pig brain. AB - Using a vascular brain perfusion model in the guinea-pig, the net uptake of [35S] GSH by the brain was found to be linear and similar in various regions during 10 min perfusion. Dual labeled [35S and 3H] GSH taken up by the brain had the same isotope ratio as the injected stock whether or not gamma- glutamyl transferase was inhibited. Greater than 96% of brain uptake of [35S]-cysteine-labeled GSH and [3H]-glycine-labeled GSH were in intact form. Transcytosis of [35S]-GSH from lumen into brain parenchyma was demonstrated using a capillary depletion technique. Both GSH and GSH-monoethyl ester inhibited [35S]-GSH transport. Thus, we have demonstrated blood-brain barrier extraction of circulating GSH in a brain perfusion model, and the transcytosis of intact GSH into the brain parenchyma without breakdown. PMID- 8198603 TI - Prohibitin expression during cellular senescence of human diploid fibroblasts. AB - Prohibitin is an evolutionarily conserved gene postulated to possess tumor suppressor activity and to contribute to the limited lifespan of human diploid fibroblast-like cells. Prohibitin mRNA and protein expression and its ability to become post-translationally modified were determined in human diploid fibroblast like cells of different in vitro ages. The expression of prohibitin mRNA and protein changes little with increasing in vitro age; however, its protein product is post-synthetically modified in younger but not older cells. These results suggest that prohibitin is similar to the retinoblastoma gene product whose anti proliferative activity remains active in older cells because it is not post synthetically modified. PMID- 8198604 TI - Taste receptor proteins directly extracted by liposome from intact epithelium of bullfrog tongue. AB - This work first provides that epithelial membrane proteins can be directly transferred from animal intact tissue to liposome. Bullfrog tongue was treated with a specially modified liposome that contains an artificial boundary lipid. Glossopharyngeal nerve responses of the treated tongue were then measured to five taste stimuli (NH4Cl, L-Ala, sucrose, L-Leu, and quinine hydrochloride). The liposomal treatment caused remarkable changes of the taste nerve responses. Gel electrophoretic analysis of the treated liposome revealed that the direct transfer of proteins, likely taste receptor, certainly occurred from the tongue epithelium to the liposome. PMID- 8198605 TI - Cloning and expression of a cDNA encoding the homologue of Ran/TC4 GTP-binding protein from Plasmodium falciparum. AB - In our effort to identify and study proteins that are important for the progression of the malaria parasite, Plasmodium falciparum, through the cell cycle, we have cloned and sequenced the homologue of Ras-related nuclear protein Ran/TC4 (PfRan). The predicted peptide sequence of PfRan is 214 amino acids long and contains consensus motifs of the Ras superfamily. The expression of a 1.7 kb PfRan transcript changes during the cell cycle, reaching a peak at the trophozoite stage of growth of the parasite. The recombinant PfRan binds GTP similar to other Ras-like proteins. PMID- 8198606 TI - Stage-specific changes in protein phosphorylation during spore germination in Dictyostelium: role of calmodulin. AB - Extensive protein phosphorylation occurs during all phases of spore germination in Dictyostelium discoideum. The developmental changes were prevented when germination was inhibited by inhibitors of calmodulin function. In addition, differences in patterns of phosphorylation were detected based upon the method of spore activation. Several phosphoproteins were lost in heat activated as compared to autoactivated spores. In spite of the fact that several aspects (i.e. autoactivation, emergence) are calmodulin-dependent, there was no evidence that calcium- or calmodulin-dependent protein kinase activity is present during any phase of spore germination. This suggests that other CaM-dependent processes mediate the diverse aspects of spore germination in D. discoideum. PMID- 8198607 TI - Human melanoma cells express functional endothelin-1 receptors. AB - Current evidence suggests that endothelium-derived factors enhance human melanoma vascular invasion. Therefore, we studied human melanoma cell expression of receptors to the endothelium-derived peptide, endothelin-1 (ET-1), and determined if they respond to ET-1 with proliferation and chemokinesis. Human metastatic melanoma cell lines were found to have specific, saturable, high affinity ET-1 binding. Northern analysis and competitive inhibition studies confirmed that melanoma cells express the ETB receptor isoform. Ten nanomolar ET-1 caused an 8.2 to 25.5-fold increase in intracellular free calcium. ET-1 was found to be a weak mitogen for melanoma cells, however, melanoma cell chemokinesis was significantly increased by ET-1. These data suggest that ET-1 may be involved in providing a chemokinetic and growth factor environment that enhances perivascular proliferation and invasiveness of melanoma cells. PMID- 8198608 TI - Purification and characterization of a novel metalloprotease from human brain with the ability to cleave substrates derived from the N-terminus of beta-amyloid protein. AB - The main component of amyloid plaques in Alzheimer's disease (AD) is the beta amyloid peptide (beta/A4), derived from beta-amyloid precursor proteins (beta APPs). In order to identify proteases possibly involved in the cleavage at the N terminal site of beta/A4 a chromogenic peptide corresponding to this region of beta-APP was used. Here the purification and characterization of a new human brain protease with the ability to cleave the beta-APP peptide as well as beta APP in vitro are described. The enzyme has a molecular mass of 100 kDa and belongs likely to the class of metalloproteases. It should further be named "MP100". The enzyme has a very broad substrate specificity in vitro. PMID- 8198609 TI - Characterization of the G-protein linked orphan receptor GPRN1/RDC1. AB - Site specific antibodies were raised against the second intracellular loop of the G-protein coupled orphan receptor GPRN1 for analysis of receptor protein expression from a number of sources. Immunoblot analyses showed GPRN1 to be a 60 kDa membrane bound glycoprotein. It was found in AR4-2J, PC12 and SK-N-MC cell lines. High amounts of GPRN1 were found in rat stomach, liver, lung, brain, small intestine and pancreas, with lower amounts in spleen and kidney: none was detectable in rat heart. This distribution differs markedly from that of the closely related orphan receptor RDC1. The receptor shows high evolutionary conservation: immunoreactive 60 kDa GPRN1 was detected in membrane glycoprotein fractions from the livers of rat, toad, chick, stingray and shark. It is therefore predicted that GPRN1 and RDC1 represent two tissue specific subtypes of a 60 kDa receptor for a ligand which has likely been highly conserved throughout evolution and which is active upon many organs of the body. PMID- 8198610 TI - Identification of dnaK multigene family in Synechococcus sp. PCC7942. AB - Three dnaK gene homologs have been cloned and sequenced from cyanobacterium Synechococcus sp. PCC7942 using a set of primers designed from two conserved regions of known dnaK genes. This is the first example of triple genes for dnaK from prokaryotic cells. These three genes were derived from different loci of the chromosome. PMID- 8198611 TI - Free radical bombing of spermatozoa in spermatic granuloma: an attempt to prevent autoimmune switch-on. AB - Even though vasectomy-associated reactions in subjects are established, the biochemical attributes of the granuloma cells enabling them to potently dispose of the accumulating spermatozoa remain unelucidated. This study demonstrates a careful "free-radical bombing" within the granuloma interior to efficiently disintegrate all the structural elements of the sperm cells, especially the proteins. A free radical triggered and instantaneous protein-disposal could be important in avoiding early post-vasectomy autoimmune triggering. PMID- 8198612 TI - Bioassay discrimination between nitric oxide (NO.) and nitroxyl (NO-) using L cysteine. AB - Nitroxyl (NO-) is the one-electron reduction product of nitric oxide (NO.). Recently, NO- generating compounds were shown to possess potent vasorelaxant activity and this was attributed to the ready conversion of NO- to NO.. Because of its metastable character, direct chemical detection of NO- or its conjugated acid, HNO, has not been accomplished yet. In order to gain further insight into the cellular mode of action of NO- generating compounds we aimed at finding a means to discriminate NO- from NO. by bioassay. Using isolated rat aortic rings in organ baths, we here show that high concentrations of L-cysteine cause complete inhibition of the vasorelaxant response to NO- (generated from Angeli's salt and sodium nitroxyl) whereas responses to authentic NO. and S nitrosocysteine are largely enhanced. Preliminary results indicate that the inhibition by L-cysteine of NO- activity may be mediated in part by enzymatic and non-enzymatic mechanisms. Whether or not NO- generating compounds will have promising therapeutic potential as a new class of NO.- donors will not least depend on their interference with enzymatic routes susceptible to inhibition by NO-. PMID- 8198613 TI - Expression and cDNA cloning of human HMGI-C phosphoprotein. AB - The HMGI family contains three members: I, Y and I-C. HMGI and HMGY are alternative splicings of the same gene and are essential transcription factors at several genetic loci. HMGI-C is transcribed from a different gene and is observed only in highly transformed cells. This work shows that human I-C is present in a more restricted range of cell types than I/Y and is absent from hemopoietic cells, as noted for mouse I-C. However, high expression in a human hepatoma line allowed the cloning of the cDNA and 812 bp of 5'-untranslated, 330 bp of coding and 58 bp of 3'-untranslated DNA were sequenced. The open reading frame showed 4 amino acid substitutions and one additional amino acid when compared to mouse I C, none of them in the basic DNA binding motifs. PMID- 8198614 TI - High glucose condition activates protein tyrosine phosphatases and deactivates insulin receptor function in insulin-sensitive rat 1 fibroblasts. AB - To investigate the mechanism for the impairment of insulin receptor kinase activity induced by high glucose (HG) in Rat 1 fibroblasts that expressed human insulin receptors (HIRc), we measured protein tyrosine phosphatase (PTPase) activity in HG cells. Incubating HIRc cells for 4 days in 27 mM D-glucose (HG) stimulated cytosolic PTPase activities, but not particulate PTPase activity as determined by two methods using the dephosphorylation of insulin receptors. Furthermore, PTP1B, a major non-transmembrane PTPase in the cytosolic fraction, was increased in HG cells according to Western blots. These results indicate that desensitization of insulin receptor function by a high glucose condition is associated with the activation of PTPase activity. PMID- 8198615 TI - The prevention of collagen breakdown in bovine nasal cartilage by TIMP, TIMP-2 and a low molecular weight synthetic inhibitor. AB - Interleukin-1 stimulated bovine nasal cartilage fragments were cultured in the presence and absence of various metalloproteinase inhibitors. Tissue inhibitor of metalloproteinases (TIMP) and tissue inhibitor of metalloproteinases-2 (TIMP-2) completely blocked the release of collagen from the cartilage but were unable to prevent the release of proteoglycan. Similarly, a low molecular weight synthetic inhibitor (BB87) inhibited collagen release in a dose dependent manner, but was unable to inhibit proteoglycan release at the same concentrations. Significantly greater concentrations of inhibitor than those required to block collagen release did, however, block proteoglycan release. These results indicate that the therapeutic use of naturally occurring or synthetic inhibitors may provide a means of modifying the destruction of connective tissue proteins occurring in the arthritides and other connective tissue pathologies. PMID- 8198616 TI - 1994 Regional meetings of the American College of Rheumatology. Abstracts. PMID- 8198617 TI - Cloning and structure of the human corticotrophin releasing factor-binding protein gene (CRHBP) AB - The human CRF-binding protein gene has been cloned and mapped to the distal region of chromosome 13 and loci 5q in the mouse and human genomes, respectively. The gene consists of 7 exons and 6 introns. The mature protein has 10 cysteines and 5 tandem disulfide bridges 4 of which are contained within exons 3, 5, 6, and 7. One bridge is shared by exons 3 and 4. The signal peptide and the first 3 amino acids of the mature protein were coded for by an extreme 5' exon. Primer extension analyses revealed the transcriptional initiation site to be located 32 bp downstream from a consensus TATA box. The promoter sequence contained a number of putative promoter elements including an AP-1 site, three ER-half sites, the immunoglobulin enhancer elements NF-kappa B and INF-1, and the liver-specific enhancers LFA1 and LFB1. PMID- 8198618 TI - Gestational diabetes mellitus. PMID- 8198619 TI - Failure to "fully communicate": catastrophic results. Case in point: Baptist Medical Center v. Wilson 618 So. 2d 1335--AL (1993). PMID- 8198620 TI - Characterization of plant L-isoaspartyl methyltransferases that may be involved in seed survival: purification, cloning, and sequence analysis of the wheat germ enzyme. AB - Protein carboxyl methyltransferases (EC 2.1.1.77) that catalyze the transfer of a methyl group from S-adenosylmethionine to L-isoaspartyl and D-aspartyl residues in a variety of peptides and proteins are widely, but not universally, distributed in nature. These enzymes can participate in the repair of damaged proteins by facilitating the conversion of abnormal L-isoaspartyl residues to normal L-aspartyl residues. In this work, we have identified L-isoaspartyl methyltransferase activity in a variety of higher plant species and a green alga. Interestingly, the highest levels of methyltransferase were located in seeds, where the problem of spontaneous protein degradation may become particularly severe upon aging. The wheat germ methyltransferase was purified as a monomeric 28,000-Da species by DEAE-cellulose chromatography, reverse ammonium sulfate gradient solubilization, and gel filtration chromatography. The purified enzyme recognized a variety of L-isoaspartyl-containing peptides, but did not recognize two D-aspartyl-containing peptides that are substrates for the mammalian enzyme. The partial amino acid sequence was utilized to design oligonucleotides to isolate a full-length cDNA clone, pMBM1. Its nucleotide sequence demonstrated an open reading frame encoding a polypeptide of 230 amino acid residues with a calculated molecular weight of 24,710. This sequence shares 31% identity with the L-isoaspartyl methyltransferase from Escherichia coli and 50% identity with the L isoaspartyl/D-aspartyl methyltransferase from human erythrocytes. Such conservation in sequence is consistent with a fundamental role of this enzyme in the metabolism of spontaneously damaged polypeptides. PMID- 8198621 TI - [Evaluation of the epidemiologic situation of tuberculosis in Poland and in the world]. AB - The paper describes the current epidemiological situation of tuberculosis in Poland, its trends in the last 2-3 decades and its place on comparison to the global world-wide situation. The incidence of tuberculosis in Poland declined from 182.6 per 100,000 population in 1965 to 43.2 per 100,000 in 1991, but is still at least two times higher than the average for Europe. The rate of decline for the last few decades was about 5.5% annually, but last year an increase has been observed. Among newly detected cases of tuberculosis in Poland in comparison to other European countries there is a higher proportion of young adults, of severe clinical forms, and relatively lower proportion of relapses. The annual risk of tuberculosis infection, the indicator considered as a most reliable one, which ranges from 0.01 to more than 3% worldwide, in Poland as about 0.2%. The highest risk, and prevalence of tuberculosis infection is in African and Asian countries, where there is also the highest prevalence of HIV infection, and consequently an important increase in the incidence of tuberculosis. Such an increase has also been observed in the USA and in some European countries. The increase in the incidence of tuberculosis in Europe however, could not be directly connected with the HIV infection. The current epidemiological situation of tuberculosis and its worldwide perspectives seem to be closely related to: (i) existing geographical differences in the level of the risk and prevalance of tuberculosis (ii) the level and the spread of HIV infection (iii) the difference in the demographic structure of population in different parts of the world which will determine the frequency of dual (HIV/TB) infection, (iv) the effectiveness of tuberculosis control activities, and (v) the level of migratory movements of population, particularly from countries/areas with high prevalence of tuberculosis. The recently observed increase in the incidence of tuberculosis in many parts of the world including Poland indicates clearly the importance and the necessity to constantly monitor all the changes in the epidemiological situation of tuberculosis and of AIDS/HIV infection [corrected]. PMID- 8198623 TI - Dependence of fatty acid composition of Listeria spp. on growth temperature. AB - In Listeria spp., various fatty acids are produced; by far the most common members are C15 and C17 chain length fatty acids. This pattern is rather similar in all species. At low temperatures, most of the Listeria are able to change the relative composition whereby more of the C15 fatty acids are produced, which could increase the fluidity of the bacterial cell membrane under these conditions. PMID- 8198622 TI - Ch2, a novel halophilic archaeon from an Australian solar saltern. AB - A novel halophilic archaeon, strain Ch2, was isolated from a marine solar saltern in Geelong, Australia. The fact that this organism had a dam-methylated genome suggested that it is closely related to the taxon that includes Halobacterium saccharovorum, Halobacterium sodomense, and Halobacterium trapanicum. A sequence analysis of the 16S rRNA gene (Ch2 has three copies of this gene) showed that Ch2 is phylogenetically equidistant from the genera Haloarcula and Haloferax and closely related to H. saccharovorum. The susceptibility of both Ch2 and H. saccharovorum to the recently isolated halophage HF2 supported the hypothesis that these two organisms are closely related. PMID- 8198624 TI - [The ethics of caring for the dead]. PMID- 8198625 TI - No significant effect of calcium and vitamin D supplementation on blood pressure and calcium metabolism in elderly Chinese. AB - To examine the effects of calcium and vitamin D supplementation on blood pressure and calcium metabolism, we conducted a randomized, double-blind, 2 x 2 factorial intervention study in 58 institutionalized elderly persons. The subjects were randomly allocated into four groups to receive: (1) calcium (800 mg/day) + vitamin D3 placebo, (2) vitamin D3 (5 micrograms/day) + calcium placebo, (3) calcium + vitamin D3, or (4) placebo treatment. Blood pressure was measured and a 24-h urine specimen and an 8-h fasting blood sample were collected at the time of recruitment before treatment and after 2 and 11 weeks of treatment. The changes in urinary calcium levels and plasma vitamin D concentrations were highly correlated with the corresponding treatments in each group, indicating good compliance. Mean systolic blood pressure decreased slightly during intervention in the group given calcium supplements, but increased slightly in the group given calcium + vitamin D. The data suggest that oral supplements of 800 mg calcium or 5 micrograms vitamin D daily produce no significant effect on blood pressure in the elderly in 11 weeks. PMID- 8198626 TI - Weaning patients from mechanical ventilation using gastric pH. PMID- 8198627 TI - Idiopathic intracranial hypertension and facial diplegia. PMID- 8198628 TI - Nylestriol replacement therapy in postmenopausal women. A three-year prospective study. AB - A three-year prospective study was carried out in 283 postmenopausal women to evaluate the effects of a long-acting estriol derivative-nylestriol. The women were randomly assigned into 3 groups: group A (136 cases, nylestriol 2 mg/2 wk), group B (97, nylestriol 1 mg/2 wk) and group C (50, placebo/2wk). LDL-C decreased and HDL-C increased after 3 months of medication (P < 0.05), but TC and TG not significantly changed in any group (P > 0.05). No changes of lipids were found in group C (P > 0.05). Serum ALP, Ca/Cr and Hpr/Cr in fasting urine decreased in 3 months in both group A and B (P < 0.05), but not in group C (P > 0.05). Forearm bone mineral content loss was restrained in groups A and B (P > 0.05), but decreased markedly in group C (P < 0.01). The Kupperman index scores decreased by about 50% after 3 months and 80% in 12 months in groups A and B. Nylestriol induced mild stimulatory effect on the uterine endometrium, and addition of 6 mg of provera daily for 7-10 days every 6 months is recommended. Nylestriol exhibited no obvious effect on the breast. This study demonstrated that nylestriol can be used as an effective and acceptable estrogen replacement therapy for postmenopausal women. PMID- 8198629 TI - AIDS and dentistry. PMID- 8198630 TI - Emergency medicine, abortion and the healing tradition. PMID- 8198631 TI - Glucocorticoid-induced impairment in declarative memory performance in adult humans. AB - Glucocorticoids (GCs) have a variety of effects on the brain including site preferential, inhibitory effects on hippocampal neurons. In the case of dexamethasone (DEX), extended rather than single-dose treatment in vivo may be required for binding to brain rather than peripheral (e.g., pituitary) GC receptors and for maximizing other biologic effects in hippocampus (e.g., GC receptor downregulation, inhibition of glucose transport). Based on the contributory role of hippocampal neurons in declarative memory performance, we investigated the cognitive consequences of DEX treatment in normal adult human subjects, hypothesizing a decrease in declarative memory performance after extended but not overnight treatment. Double-blind, placebo-controlled treatment with DEX was given at 2300 hr for four consecutive days (0.5, 1, 1, 1 mg, respectively). Plasma sampling (0800 and 1600 hr) and cognitive testing (1600 hr) were performed on study days 0 (baseline), 1, and 4, and 7 d posttreatment. Repeated-measures ANOVA found a significant interaction between study day and treatment condition for correct recall during a paragraph recall task [F(3,51) = 3.52, p = 0.02]. DEX (n = 10) in comparison to placebo (n = 9) treatment decreased correct paragraph recall on study day 4 [F(1,17) = 5.01, p = 0.04] and study day 11 [F(1,17) = 5.82, p = 0.03], with the lowest level of performance occurring on day 4 followed by a return toward baseline performance level by day 11. In the placebo-treated subjects, correct paragraph recall improved over the course of treatment, consistent with practice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198632 TI - How can hospitals ration drugs? Fairness is at issue. PMID- 8198633 TI - Radon exposure and lung cancer. PMID- 8198634 TI - [Valvular cyst and atrioventricular canal in a child with trisomy 21]. AB - A child with Down's syndrome with an atrioventricular canal of ostium primum type had also a blood cyst of the mitral valve. Aside more frequent complex heterotopic cysts due to migration anomalies, simple cysts are rare with only 27 cases described in medical literature. They are often symptomatic and are cured by surgical removal. Our hypothesis, in accord with recent embryologic observations, is that simple cysts situated close to the valves and fibrous ring of the heart may result from heteroplastic change of tissue coming from primitive pericardial mesothelium. This primitive mesothelium participates to the formation of the fibrous skeleton of the heart. PMID- 8198635 TI - [Jaffe-Campanacci syndrome. Report of a case]. AB - Jaffe-Campanacci syndrome is a rare entity characterized by disseminated non ossifying fibromas in association with extraskeletal congenital anomalies: cutaneous, genital, ocular and cardiovascular. Mental retardation is also frequently observed. Pathological fractures are the usual mode of revelation. We report one case original because of causal discovery during orthodontic check-up and because of extraskeletal anomalies not previously described. In fact the true incidence of this syndrome is probably underestimated because of unrecognized features. PMID- 8198636 TI - [Myoepithelioma (or myoepithelial cell adenoma). Report of a case]. AB - One case of myo-epithelioma occurring in the parotid gland is reported. This tumor was composed of spindle cells. The diagnosis was confirmed by ultrastructural and immunohistochemical analysis demonstrating myofilaments aggregation pattern and positive staining for S100-protein and keratin antibodies. Of all salivary gland tumors, myo-epithelioma accounts for less than 1% of the total and has a good prognosis. Conservative surgical management is curative. PMID- 8198637 TI - [Encephalomyelitis with cavitary necrosis of the white matter. A clinico pathologic study]. AB - The authors report the clinico-pathological study of an encephalomyelitis with necrotic cavitation of the white matter occurring in a 61-year-old female. The disease of sudden onset progressed slowly to the death, 20 months after the onset of the first symptoms. They stress the rarity of the entity and the difficulties to establish the diagnosis clinically. The nosological situation of the condition is discussed and compared with the previously reported cases. PMID- 8198639 TI - [Calcifying fibrous pseudotumor]. AB - The case of a 17-year-young woman with Calcifying Fibrous Pseudotumor is reported. This observation emphasizes 1) A distinctive histologic appearance and the broad spectrum of this entity, 2) The differential diagnosis to consider, 3) The excellent prognostic and the low risk of local recurrence. PMID- 8198638 TI - [Sarcoidosis and non-Hodgkin's lymphoma. A non-fortuitous association]. AB - The simultaneous disclosure of a lymphoblastic B cell lymphoma and sarcoidosis is reported herein. The initially undiagnosed sarcoidosis leads to discuss the differential diagnosis of a sarcoid-like reaction associated to the lymphoma. The association of sarcoidosis and malignant lymphoproliferative disease is not fortuitous; nevertheless the simultaneity of the two diagnoses, the lymphoblastic type of the lymphoma and the colocalization of granulomatous and lymphomatous lesions in lung and liver are unusual features. PMID- 8198640 TI - [Dermatosis, a clue to diagnosis: necrolytic migratory erythema capable of inclusion in the glucagonoma syndrome]. PMID- 8198641 TI - [Cystic hypersecretory hyperplasia of the breast. A rare diagnosis in breast pathology]. PMID- 8198642 TI - [Does nevo-cellular nevus of the colonic mucosa exist? Report of a case]. PMID- 8198643 TI - [What is the value of guided abdominal fine needle biopsy in 1994]. PMID- 8198644 TI - [Fine needle aspiration cytology of the viscera. Intra-abdominal and retroperitoneal masses]. PMID- 8198645 TI - [Intraductal mucin-secreting tumors of the pancreas. Nosologic discussion of two cases of villous tumor of Wirsung's duct and a case of mucinous ductal ectasia]. AB - Intraductal mucin-producing tumors of the pancreas are rare, recently described tumors; they have a better prognosis than usual ductal carcinomas of the pancreas. We report two cases of villous tumor of the main pancreatic duct and one case of mucinous ductal ectasia, with histochemical and immunohistochemical study. PMID- 8198646 TI - [Granular cell tumors of the breast]. AB - The granular cell tumor was first described by Abrikossoff who referred to that lesion as myoblastoma. This lesion is mainly observed in soft tissues and is exceptionally found in the mammary gland. Among the 159 cases of breast granular cell tumor reported in the literature, only 121 have been well documented. Tumors occurred in 15 to 74 year old patients and in only 9.8% of the tumors discovered in males. In breast this tumor may mimic a carcinoma like in the three cases reported. The intra-operative diagnosis on frozen sections may be particularly difficult and the risks to overdiagnose a carcinoma are not negligible and must be known. The diagnosis on paraffin sections is much more easier than on frozen sections. The immunostaining procedures (anti p S100) and electron easier than on frozen section. The immunostaining procedures (anti p S100) and electron microscopy are mainly interesting to document the histogenetic hypotheses. The schwannian origin of the tumor is favoured in most of the recent studies. The granular cell tumors are usually benign and malignant tumors account for only 2.5% of those diagnosed in the breast. PMID- 8198647 TI - Contribution of genetic disorders to neonatal mortality in a regional intensive care setting. AB - We examined the contribution of chromosomal abnormalities, mendelian disorders, and birth defects to mortality in a regional neonatal intensive care unit by medical record review of neonatal deaths in that unit. Of a total of 296 infant deaths during the 5-year period June 1986 to May 1991, 69 (23.3%) had a genetic disorder. By diagnostic category, 18.8% had a chromosomal abnormality, 10.1% had a mendelian condition, 42% had a single primary defect in development, and 29% had an unrecognized pattern of malformation. The rate of autopsy and genetic evaluation differed markedly between these diagnostic categories. A comparison was made of underlying cause of death determined from medical records with underlying cause as classified by vital statistics nosologic procedures. No death certificate was on file for two of the deaths; for the remaining 67, 27 (40.3%) had an erroneous or misleading underlying cause of death as determined from vital statistics. The important contribution of genetic disorders to neonatal mortality in this high-risk population and the relative underrecognition of these disorders by vital statistics sources indicate that efforts aimed at reducing neonatal mortality will require a full range of preventive health activities, including preconception, prenatal and perinatal assessment, and counseling. Improved data collection techniques need to be developed to understand the contribution of this group of conditions to total neonatal mortality. PMID- 8198648 TI - Ultrasound prediction of fetal pulmonary hypoplasia in pregnancies complicated by oligohydramnios and in cases of congenital diaphragmatic hernia: a review. AB - The objective of this review is to discuss the current knowledge of fetal pulmonary hypoplasia and to summarize the clinical significance of the many ultrasound methods for predicting pulmonary hypoplasia in pregnancies complicated by oligohydramnios due to spontaneous rupture of the fetal membranes and in cases complicated by fetal congenital diaphragmatic hernia. We concluded that the presence or absence of polyhydramnios, fetal breathing movements, mediastinal shift, thoracic position of the stomach, fetal breathing-related nasal and oropharyngeal fluid flow, ductal flow velocity modulation, and gestational age at onset and severity of ventricular disproportion as useful markers for predicting fetal pulmonary hypoplasia is a productive area for continued research. All studies show that there is a clear association between most of these markers and pulmonary hypoplasia. However, these markers have not been studied together in a large number of cases, and comparisons between each of the markers is unknown. PMID- 8198649 TI - Fetal cardiac effects of oral ritodrine tocolysis. AB - The beta-sympathomimetic oral tocolytic ritodrine can cause maternal tachycardia and hypotension, and may cross the placenta. A new echocardiographic technique has been developed to explore fetal and placental ritodrine effects. Values in 76 healthy historic controls were compared to 18 studies in 16 patients performed while receiving stable oral ritodrine therapy, measured both at baseline and 30 minutes after a dose. Data collected included maternal pulse and blood pressure (BP), fetal cerebral and umbilical Doppler waveforms, and fetal heart rate. A new index of fetal myocardial contractility, combined ventricular shortening fraction, was derived from two-dimensionally directed M-mode. Maternal pulse and BP, fetal heart rate and heart size, and all Doppler indices were normal, without demonstrable dose-response effects. In the control subjects, combined ventricular shortening fraction fell with increasing gestational age (combined ventricular shortening fraction = -0.27 estimated gestational age + 49; r = 0.27; P < or = 0.02; standard error of the estimate, 11%). However, combined ventricular shortening fraction in ritodrine patients was abnormally decreased in 72% of cases. The mean index in normal subjects was 43 +/- 5%, but in ritodrine patients it was only 31%. We conclude that a history of premature labor or oral ritodrine, or both, is associated with reduced shortening fraction. Since there was no change in placental resistance, cerebral hypoxia, fetal heart rate, or heart size (preload), then low shortening fraction may be due to increased fetal systemic vascular resistance (BP) or decreased myocardial contractility. PMID- 8198650 TI - Increased nucleated erythrocytes in an infant with congenital hyperinsulinism. AB - A markedly elevated peripheral nucleated erythrocyte count is reported in a term nonmacrosomic infant with congenital hyperinsulinism born to a nondiabetic mother. With control of hypoglycemia and hyperinsulinism, the count declined to normal. A relationship of hyperinsulinism and erythropoiesis, not related to fetal hypoxemia, is considered. PMID- 8198651 TI - Electroconvulsive therapy in a twin pregnancy: a case report. AB - We present a case of twin gestation complicated by severe depression and psychotic behavior; the mother was treated with electroconvulsive therapy (ECT). She had received multiple medications for treatment of her depression earlier during the first part of the pregnancy. However, frequent use of ECT later in the course of pregnancy did not result in adverse fetal outcome as is evident from normal fetal surveillance tests. We conclude that, when indicated, ECT during pregnancy improves maternal condition and does not adversely affect fetal well being. PMID- 8198652 TI - Idiopathic cerebral infarction and upper limb ischemia in neonates. AB - Idiopathic cerebral infarction is very rare in neonates and has been described as being associated with upper extremity ischemia in a handful of cases. We report on two cases in which no etiology was found and review the literature on this interesting entity. PMID- 8198653 TI - Analysis of 309 cases of esophageal atresia for associated congenital malformations. AB - Three hundred nine cases of esophageal atresia were retrospectively investigated. One hundred and sixty-two (52.4%) had associated congenital malformations. The total number of malformations was 357. The eight groups of malformations in decreasing order of frequency were as follows; cardiac, 72 cases (23.3%); musculoskeletal, 55 cases (17.8%); anointestinal, 50 cases (16.2%); genitourinary, 45 cases (14.6%); head and neck, 31 cases (10.0%); mediastinal, 26 cases (8.4%); chromosomal, 17 cases (5.5%); pulmonary, 6 cases (1.9%). Of the 162 cases with associated malformations, 83 (51.2%) had a single group of malformations, 41 (25.3%) had two groups of malformations, and 38 (23.5%) had three or more groups of malformations. More than 50% of pulmonary (83.3%), head and neck (77.4%), chromosomal (58.8%), and mediastinal malformations (53.8%) were found in association with cardiac malformations. The frequency of associated malformations in esophageal atresia cases was found to be increased significantly during the investigated interval. Early gestational age and lower birthweights were significantly correlated with higher rates of malformations. The survival rates of patients with esophageal atresia was also found to be significantly increasing over time. The mean survival rates over 32 years for groups with and without malformations were 38.3% and 70.7%, respectively, and were statistically significant. The mean survival rates of the same groups in the last 5 years were found to have changed dramatically, rising to 62.9 in the group with malformations and to 100% in the group without malformations; again, the difference is significant. PMID- 8198654 TI - Right-sided diaphragmatic hernia associated with superior vena cava syndrome. AB - The term "hydrops fetalis" denotes generalized fetal edema, a condition that differs from localized edema confined to head, extremities, or body cavities. This report illustrates a case of right-sided diaphragmatic hernia associated with severe edema of the head, polyhydramnios, small hydrothorax, and ascites with an antenatal diagnosis of hydrops fetalis. At autopsy, edema was confined to the head and neck and the peritoneal sac. The mechanisms responsible for these forms of localized edema were obstruction of the superior vena cava and hepatic veins, respectively. Localized fetal edema may be confused with hydrops fetalis. Fetal edema of the head and neck may result from obstruction of the superior vena cava by abnormal mediastinal structures. PMID- 8198655 TI - Acute maternal and fetal cardiovascular effects of caffeine ingestion. AB - Little data exist regarding the acute maternal and fetal cardiovascular effects of caffeine ingestion. The purpose of this study is assess the cardiovascular effects of caffeine ingestion in pregnant subjects and their fetuses. We examined seven caffeine-naive gravidas longitudinally at 25.7 (SE +/- 0.7) and 36.1 (+/- 0.7) weeks' gestation, before and after ingestion of a caffeine citrate solution (100 mg/m-2 body surface area). Maternal pulse, blood pressure, fetal heart rate, and fetal heart rate accelerations were determined before and after caffeine ingestion. Uterine artery, fetal aorta, and umbilical artery flow velocity waveforms were examined at similar intervals. Significant before and after caffeine differences, regardless of gestational age, were noted for maternal pulse (85.1 vs 74.2 beats/min), diastolic blood pressure (65.9 vs 73.8 torr), mean arterial blood pressure (81.5 vs 87.5 torr), uterine artery systolic-to diastolic (S/D) ratio (1.9 vs 2.4), fetal heart rate (144.6 vs 135.4 beats/min), and fetal heart rate accelerations (1.6 vs 4.2 per 30 minutes). Differences for fetal aortic and umbilical artery S/D ratios were not significant with respect to caffeine administration. Fetal aortic peak velocities increased with caffeine (85.5 vs 130.2 cm/sec) and the increase was augmented with advancing gestational age. We conclude that maternal ingestion of modest amounts of caffeine citrate in caffeine-naive subjects significantly affects both the fetal and maternal cardiovascular systems. PMID- 8198656 TI - Brain temperature discriminates between neonates with damaged, hypoperfused, and normal brains. AB - Brain temperature depends on the balance of cerebral heat production and heat loss via cerebral circulation and head surface. We investigated whether brain temperature and heat loss via the head surface differed in neonates with abnormal cerebral metabolism or circulation. We measured the core temperature of the head noninvasively by the zero-gradient method, skin temperature of the head, the heat flux from the head, and esophageal and operative environmental temperature in seven healthy neonates, seven neonates with cerebral damage, and two neonates with cerebral hypoperfusion caused by an incurable congenital heart disease. Cerebral blood flow velocity in the anterior cerebral artery and systemic blood pressure were also measured. Brain temperature profile was measured in two premature infants with external ventricular drainage. Core temperature of the head, considered to represent brain temperature, was up to 1.5 degree C higher in infants with cerebral hypoperfusion than in normal neonates. The core temperature of the head was higher than the esophageal temperature in all except two infants with the most severe cerebral damage. The difference between core temperature of the head and esophageal temperature was 0.72 +/- 0.12 degree C in normal neonates, 0.16 +/- 0.4 degree C in infants with cerebral damage, and ranged from 0.9 to 1.2 degree C in infants with cerebral hypoperfusion. The relationship of core of the head to esophageal temperature discriminated between all 16 newborn infants according to their brain pathologic condition, except one infant with a mild ischemic-hypoxic encephalopathy. In conclusion, brain temperature depends on cerebral perfusion and level of brain injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198657 TI - Ratios between the abdominal circumference, head circumference, or femur length and the transverse cerebellar diameter of the growth-retarded and macrosomic fetus. AB - The purpose of our investigation was twofold: to provide normative data for the ratios between head circumference and cerebellum, abdominal circumference and cerebellum, and femur length and cerebellum; and to evaluate the predictive accuracy of an abnormal ratio in the detection of growth retardation and macrosomia. Data on 675 women with normal gestations between 14 and 42 weeks were used to estimate reference curves for the three ratios to be evaluated. We then compared the ratios of 34 fetuses with intrauterine growth retardation and 28 macrosomic fetuses to the control group. Of the three ratios that we investigated, abdominal circumference to transverse cerebellar diameter was the most efficacious. However, the sensitivity of this ratio for the detection of intrauterine growth retardation and macrosomia was only 52.9% and 46.6%, respectively. A ratio between head circumference, abdominal circumference, or femur length and the transverse cerebellar diameter cannot reliably distinguish between normally growing fetuses and those that are growth retarded or macrosomic. PMID- 8198658 TI - A simplified phenytoin regimen for preeclampsia. AB - The objective of this study was to assess the feasibility of giving phenytoin to a group of mild preeclamptic women in a universal dosing scheme comparable to that typical of magnesium sulfate administration. Serum phenytoin levels were measured at regular intervals for 32 hours following a 1 g intravenous loading dose in 14 patients. A second group of 14 women received 500 mg orally to supplement the 1 g initial dose and had serum levels similarly measured. The resultant serum levels are described, and the effect of maternal weight analyzed. The average serum phenytoin level in the first 14 women given the 1 g loading dose fell to 10 micrograms/mL approximately 12 hours after treatment. Serum levels plateaued above this threshold in the 14 women given 500 mg of additional medication orally 10 hours after treatment initiation and were maintained for an additional 14 hours before decline was observed. The serum levels resulting from the initial 1 g loading dose were analyzed 8 hours after treatment initiation in the entire group of 28 women according to body weight, and a clinically significant effect of weight on serum level was observed only at the extremes of weight. We conclude that a universal dosing scheme comparable to that typically used for magnesium sulfate is feasible for phenytoin administration to preeclamptic women. PMID- 8198659 TI - Prenatal sonographic evidence supporting an in utero developmental etiology of Mobius sequence. AB - Mobius sequence features masklike facies with sixth and seventh nerve palsy and frequently micrognathia thought to result from a neuromuscular deficiency in early movement of the mandible. Failure to thrive in infancy is commonly due to feeding and aspiration difficulties. We present the first description of prenatal sonographic findings associated with this lesion, which also support an in utero developmental etiology of this rare condition. PMID- 8198660 TI - Fetal liver biopsy for prenatal diagnosis of carbamoyl phosphate synthetase deficiency. AB - Carbamoyl phosphate synthetase deficiency is a type of an inborn error of metabolism with a poor prognosis. Carbamoyl phosphate synthetase is a liver specific enzyme, and its deficiency can only be diagnosed by enzyme assay using liver biopsy specimens. A pregnant woman at risk for carbamoyl phosphate synthetase deficiency was evaluated for the purpose of prenatal diagnosis of the condition. Fetal liver biopsy was performed at the 22nd week of gestation. The results of enzyme assays on fetal liver biopsy revealed normal enzymatic activity and the diagnosis of carbamoyl phosphate synthetase deficiency was ruled out prenatally. Methods and safety of fetal liver biopsy are discussed. Measurements of activity of liver-specific enzymes were evaluated with respect to methodology and manner of assessment. Prenatal diagnosis of deficiencies in liver-specific enzymes, which have hitherto been considered difficult to detect before birth, has now become possible. PMID- 8198661 TI - Effect of corticosteroids on the maturation of neutrophil motility in very low birthweight neonates. AB - Neutrophil (PMN) chemotaxis and chemokinesis were longitudinally studied in a group of 17 neonates with birthweights between 750 and 1250 g. Five of the 17 neonates were treated with prenatal betamethasone to attempt to prevent hyaline membrane disease, six received postnatal dexamethasone in an effort to reduce bronchopulmonary dysplasia, three received both, and three were not treated with corticosteroids. The group of 17 neonates were tested on four separate occasions: (1-2, 3-4, 7-8, and 10-14 postnatal days). PMN chemotaxis and chemokinesis were determined using a standard micropore filter assay. A group of 36 adults was used as additional controls. There were no significant differences noted in PMN chemotaxis or chemokinesis for the corticosteroid vs the noncorticosteroid treated groups. In the total group of 17 neonates, there was depression in PMN chemotaxis compared with adult values, which lasted at least through postnatal day 8. By day 13 to 14, PMN chemotactic values were similar to those of adults. In contrast, chemokinesis, was depressed during the initial 14 days (except for the first 2 postnatal days). These data suggest that perinatal corticosteroid administration does not affect PMN motility in newborn infants. PMID- 8198662 TI - Motor and cardiac response during habituation testing: demonstration of exaggerated cardiac reactivity in a subgroup of normal human fetuses. AB - In this study we wanted to determine: (1) whether or not a relationship existed between the rate of habituation of the fetal motor response and changes in the fetal heart rate (FHR), and (2) if this relationship could be used to identify a subgroup of fetuses who exhibited exaggerated cardiac reactivity during habituation testing. Thirty-nine normal human fetuses between 34 and 40 weeks of gestation were evaluated. Habituation testing consisted of a 1 second vibroacoustic stimulus with a 10 second interstimulus interval for eight trials. The motor response was observed using real-time sonography, and a score of 0 to 10 was assigned for each trial based on subjective assessment of the fetal response. Motor habituation was evaluated in terms of the rate of response decrement in movement over trials (Re). Subjects were initially divided into slow and fast motor habituators based on the median of Re, and it was found that fetuses whose motor response habituated slowly displayed a significantly greater increase in heart rate compared with fetuses who habituated more rapidly (F1,37 = 8.61; P = 0.0057). Cardiac reactivity was then defined as "the average increase in FHR above the mean prestimulus value during the last half of the testing period." When the data were divided into quadrants based on medians, we identified seven (18%) fetuses who habituated rapidly but who also displayed high cardiac reactivity. We conclude that there is a significant relationship between the magnitude of the increase in FHR above baseline and the rate of motor habituation in normal human fetuses. PMID- 8198663 TI - Complete trisomy 9: case report with ultrasound findings. AB - In a case of complete trisomy 9, ultrasound findings led to prenatal diagnosis. This case is reviewed in the context of previous case reports. A 29-year-old gravida III, para II was referred at 34 weeks because of abnormal ultrasound findings. The findings included intrauterine growth retardation, Dandy-Walker malformation, a single atrium, liver calcifications, a two-vessel cord, and abnormal Doppler studies. Percutaneous umbilical blood sampling revealed complete trisomy 9. Prenatal diagnosis led to a plan of no intervention for fetal indications. Autopsy revealed facial, cardiovascular, central nervous, and skeletal findings frequently seen in complete trisomy 9. Review of all cases showed that 12 of 15 (80%) occurred in mothers younger than 35 years, 11 of 13 cases (85%) delivering after 23 weeks' gestation were small for gestational age, and 7 of 12 liveborns (58%) had cesarean delivery. Only 3 of 12 liveborns (25%) lived beyond 7 days. Abnormal ultrasound findings can be seen in cases of complete trisomy 9. Prenatal diagnosis allows the parents to make an informed decision regarding fetal intervention, which may avoid unnecessary cesarean delivery. PMID- 8198664 TI - Neonatal adrenergic blockade following single dose maternal labetalol administration. AB - A single 30 mg intravenous dose of labetalol given 20 minutes prior to cesarean delivery at 35 weeks of gestation for severe pregnancy-induced hypertension was associated with symptoms of beta-adrenergic blockade (hypoglycemia, bradycardia, hypotension) in preterm twins. The infants were subsequently found to have therapeutic labetalol concentrations (180 and 150 ng/mL) in umbilical cord blood. The pharmacology of transplacental labetalol is reviewed and potential mechanisms for neonatal beta-adrenergic blockade are discussed. PMID- 8198665 TI - Umbilical arterial catheter use: report of an audit conducted by the Study Group for Complications of Perinatal Care. AB - The Study Group for Complications of Perinatal Care through 13 of its participating neonatal intensive care units conducted an audit of umbilical artery catheter (UAC) use over 3 months. Of 1941 patient admissions, 582 (30%) had a UAC inserted and left in place for a mean of 4.9 days. The mean supplemental oxygen concentration (FIO2) at removal was 0.35 with over 55% of UACs remaining in place until FIO2 was less than 0.26. Institutional practices varied widely for positioning the catheter tip, use of heparin, and types of infusates, as did the frequency of adverse events that prompted removal of the UAC. Most institutions with multiple physicians found less consistency in practice patterns within their own units than presumed prior to the audit. Just two institutions preferred catheter placement in the abdominal aorta (low) with the others selecting a low site only after detecting a malposition below the initially sought thoracic level. All but one group routinely used heparin, although in varying concentrations and total doses. Patient weight and catheter duration were inversely correlated, with smaller patients having catheters left in place for significantly longer periods (P < 0.01). Similarly, smaller patients had a higher likelihood of catheter removal because of an adverse event; the adverse events were not necessarily related to longer duration. A significant relationship existed between positioning a catheter tip in the abdominal aorta and removal for adverse events (P < 0.05). PMID- 8198666 TI - [Effect of training on the strength of cervical muscle]. AB - The purpose of this study was to observe the effect of concentric and eccentric training on the strength of cervical muscle. The subjects were 18 adult males of whom 6 were exposed to concentric training, 6 were exposed to eccentric training, and 6 were exposed to control. Training intensity was the exertion of maximum isotonic strength on the extension, flexion, left bending and right bending of the neck. All training exercises for concentric and eccentric groups were given 10 times a set, 3 sets in a day, 3 times a week for 8 weeks. The changes in the strength of cervical muscle and in the girth of neck due to muscular training were measured regularly once a week. The results were as follows: 1) Maximum isometric strength increased significantly (p < 0.001) by 37.8% in concentric training group, and 39.6% in eccentric training group. No significant difference of strength increase was observed between concentric and eccentric training group. There was a significant decrease in the strength of cervical muscle in the early stage of muscular training, accompanied by severe muscle fatigue, but a remarkable increase in strength due to concentric and eccentric training was observed during the 8 weeks. 2) The girth of neck increased significantly (p < 0.001) by 4.9% in concentric training group, and 5.5% in eccentric training group. Significant difference of girth increase was observed after 3 and 4 weeks of muscular training of cervical muscle, meanwhile the girth of neck increased slightly by 1.3% in control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198667 TI - [Continuous noninvasive measurements of cardiac output during exercise by impedance cardiography--application to evaluation of cardiac output kinetics]. AB - The purpose of the present study was to compare the impedance derivate waveforms using spot and band electrode array and to assess applicability of automated signal processing system for cardiac output kinetics. Five healthy male subjects were tested. Cardiac output (Q) were measured using spot electrode array. Each subject performed rest-exercise transitions in leg and arm exercise on an electrically braked ergometer. The intensities of leg exercise were 25, 50, and 100 W for 5 min and those of arm exercise were 25 and 50 W. Comparisons between spot and band electrodes were made for the absolute magnitude of Q and stroke volume (SV), as well as for impedance derivative waveforms. The waveforms for spot electrodes showed less fluctuation by breathing and movement artifacts than for band electrodes. Q for spot electrodes were larger than those for band electrodes. There was a significant correlationship between oxygen uptake (Vo2) and Q. There was a significant correlationship between Q using spot electrode and Q measured by CO2 rebreathing method. Nonlinear correlation coefficient to exponential curve of Q kinetics for leg exercise was more than 0.7 and for arm exercise more than 0.4 in spite of large movement of upper body. It is suggested that the present system using spot electrodes is superior in signal processing to those for band electrodes and able to evaluate Q kinetics without multiple repetition of exercise tests. PMID- 8198668 TI - Cerebrovascular lesions in infants and children dying after extracorporeal membrane oxygenation. AB - The neuropathologic autopsy findings of a group of infants and children at Children's Hospital of Pittsburgh who died after treatment with extracorporeal membrane oxygenation (ECMO) were reviewed and tabulated. The study surveyed an 11 year period (February, 1980 to May, 1991); of 268 children receiving ECMO therapy for severe cardiopulmonary failure, 94 patients died, 70 of whom were autopsied and permission for brain examination was granted in only 44. The frequency of ischemic neuronal necrosis (50%), focal cerebral infarcts (50%), intracerebral hemorrhages (52%), and periventricular leukomalacia (41%) was higher in this group of ECMO-treated patients than that observed in the general autopsy population from which the study patients were selected. The frequency of ischemic and hemorrhagic brain lesions was similar among neonates and older infants and children. This documentation of cerebrovascular lesions in children dying after ECMO may provide a better understanding of potential brain damage in the larger population of infants and children who survive this invasive procedure. PMID- 8198669 TI - Life expectancy of children in a persistent vegetative state. AB - The persistent vegetative state (PVS) is a state of wakeful unconsciousness occurring in adults and children. Despite preservation of vegetative functions, PVS patients have a shortened life-span, although accurate information concerning this issue remains limited. The survival of children in PVS was examined to determine whether age, etiology of the vegetative state, or type of residence in which the patient lived affected the estimated survival. The data of 155,851 developmentally disabled California state residents were reviewed using the Client Development Evaluation Report (CDER). Criteria from the CDER were selected to define the vegetative state and included: lack of interaction with peers; absence of auditory, visual, and expressive or receptive language function; no hand or arm use; inability to eat, sit, roll over, or lift head; and no bowel or bladder control. There were 847 patients who met these criteria on the initial and follow-up CDERs. A product limit survival model was used to develop survival curves and to calculate the median survival time for patients grouped by age, etiology, and type of residence. Median survival (yrs) for patients who remained in PVS for the following age groups was: < 1 yr: 2.6, 1 < 2 yrs: 4.2, 2-6 yrs: 5.2, 7-18 yrs: 7.0, > or = 19 yrs: 9.9. Median survival based on etiology varied from 3.0 to 8.6 years; no consistent relationship existed between etiology and duration of survival. Survival (yrs) for patients younger than age 18 years based on type of residence included: own home: 4.5, institutions: 5.2, skilled nursing facility/private hospital: 3.2, and other community care facilities: 3.7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198670 TI - Rapid cycling in severely multidisabled children: a form of bipolar affective disorder? AB - A debilitating, regularly recurring, biphasic disorder is described in 6 severely multidisabled children. It was characterized by several days of lethargy, withdrawal, loss of abilities, irritability, and hypersomnolence followed or preceded by a high-energy state for several days during which the children slept very little, at times were euphoric, had improved mental ability, and were hyperactive. These cyclic episodes had been present for years but unexpectedly disappeared in one child. The etiology is unknown, in spite of detailed neurologic, metabolic, and endocrine investigations. All patients had family histories positive for affective disorder. Melatonin treatment helped to regulate the coexisting chronic sleep disorders of 3 children but failed to eliminate the cycles. Antiepileptic drug treatment, lithium, sedatives, stimulants, tranquilizers, and light therapy were largely ineffective. The children's symptoms and signs fit the diagnostic criteria of a bipolar affective illness, as it was modified for patients with associated neurologic disability; therefore, the patients appeared to have a unique disorder that closely resembles or is a variant of rapid cycling affective disorder. PMID- 8198671 TI - Neurologic features as initial presentations of childhood malignancies. AB - Thirty patients were examined initially because of neurologic problems and later were diagnosed as having systemic malignant disorders. Acute leukemia was the most common malignancy (36.6%), followed by neuroblastoma (33.3%), non-Hodgkin lymphoma (13.3%), rhabdomyosarcoma (10%), Ewing tumor (3.3%), and Hodgkin lymphoma (3.3%). Four of the 11 acute leukemia patients had nervous system involvement due to meningeal, orbital, or cerebellar infiltration. The complaints of the remaining patients included back pain, weakness, and difficulty in walking, all of which were caused by anemia or bone pain. Neurologic involvement in systemic malignancies, other than acute leukemia, mainly appeared as spinal cord compression (7 with neuroblastoma, 3 non-Hodgkin lymphoma, 1 rhabdomyosarcoma, 1 Ewing tumor), orbital or cavernous sinus infiltration (3 with acute leukemia, 1 rhabdomyosarcoma), and VIIth cranial nerve involvement (2 with rhabdomyosarcoma). One patient had skull infiltration without any neurologic deficit. Cerebellar signs were caused by the remote effects of cancer. It is concluded that acute leukemia is the first and neuroblastoma is the second most common malignancy among childhood systemic malignancies presenting with neurologic involvement; however, neuroblastoma is the most common cause of spinal cord compression. PMID- 8198672 TI - Development of ferritin-positive cells in cerebrum of human brain. AB - The distribution and development of ferritin-containing cells were studied immunohistochemically in the cerebrum at ages ranging from human fetuses to adults. The predominant cell type labeled with antiserum to ferritin was the oligodendrocyte. In frontal and occipital lobes, positive cells appeared at 25 weeks gestation in subcortical and periventricular white matter, and increased earlier in the white matter than in the cortex. They also appeared at 25 weeks gestation and increased continuously in infancy in the putamen and globus pallidus, as well as in the frontal and occipital lobes. This development of ferritin-positive glia may be related to the process of myelination and maturation of oligodendrocyte. PMID- 8198673 TI - Childhood stroke and lupus anticoagulant. AB - Despite extensive evaluation, the cause of many childhood ischemic strokes remains unexplained. Two children are reported with stroke and lupus anticoagulant. Both had family members with features of the antiphospholipid antibody syndrome. Children with unexplained ischemic stroke should be evaluated for lupus anticoagulant and anticardiolipin antibodies. PMID- 8198674 TI - Episodic spontaneous hypothermia with hyperhidrosis: implications for pathogenesis. AB - Unprovoked hypothermia is an unusual presenting sign. When occurring with diaphoresis it has been referred to as episodic spontaneous hypothermia with hyperhidrosis. Earlier reports described episodic, spontaneous hypothermia with hyperhidrosis in patients with agenesis of the corpus callosum and postulated a midline congenital malformation of the central nervous system. Since then, various endocrine, electrolyte, autonomic, and sleep disturbances have been described but the etiology remains undetermined. Three unrelated children are reported each of whom had an intact corpus callosum and normal endocrine function. Shivering was consistently absent despite marked symptomatic hypothermia. One child had spontaneous resolution of episodic spontaneous hypothermia with hyperhidrosis and two children responded to the antiserotonergic, cyproheptadine. It is hypothesized that specific serotonergic dysfunction in the anterior hypothalamic extrapyramidal shivering mechanism is central in the pathogenesis of this condition. PMID- 8198675 TI - Lymphoma with bilateral cavernous sinus involvement in early childhood. AB - A 4-year-old girl developed complete ophthalmoplegia with intact pupillary responses. Computed tomography and magnetic resonance imaging demonstrated a mass invading the cavernous and sphenoid sinuses and posterior ethmoidal cells. Biopsy revealed non-Hodgkin lymphoma. This patient is the youngest reported with malignant lymphoma of the cavernous sinus and the second reported with bilateral cavernous sinus involvement. PMID- 8198676 TI - Prenatal sonographic detection of basilar aneurysm. AB - Retrospective reviews document the infrequency of intracranial aneurysms in the first decade of life, with an even greater rarity in the first 2 years. Intracranial aneurysms are not known to be associated with trisomy 18. An infant is reported who was diagnosed at 32 weeks gestation as having trisomy 18. Prenatal ultrasonography identified a large cystic lesion in the posterior cerebral circulation. This small-for-gestational-age infant was born at term by dates, but renal maturation suggested a gestational age of 35-36 weeks. He survived 5 days. This is the first report of prenatal sonographic imaging of a basilar artery aneurysm confirmed by autopsy. PMID- 8198677 TI - Vascular occlusion associated with incontinentia pigmenti. AB - A 4 1/2-year-old girl with incontinentia pigmenti developed acute-onset hemiparesis. Magnetic resonance angiography revealed occlusion of the left middle cerebral artery. Many neurocutaneous syndromes have been linked to ischemic stroke syndromes. Incontinentia pigmenti has not been associated with stroke syndromes in the past; however, this report illustrates that the patient and her mother, who also has incontinentia pigmenti, may have had similar ischemic stroke events. PMID- 8198678 TI - Dermoid tumor with persistently low CSF glucose and unusual CT and MRI findings. AB - A patient with dermoid tumor, presenting with persistent hypoglycorrhachia in the absence of cerebrospinal fluid pleocytosis is reported. The presence of ring enhancements without infection, surrounding edema, and mass effect on computed tomography and magnetic resonance imaging are unusual findings for these tumors. PMID- 8198679 TI - Local fibrinolysis in cerebral venous thrombosis. AB - Extensive cerebral venous sinus thrombosis may cause death or severe neurologic sequelae. A minimally responsive 10-year-old boy with thrombosis of the superior sagittal sinus, left transverse and left sigmoid sinus, torcular, vein of Galen, and straight sinus underwent fibrinolytic therapy with urokinase during transfemoral venous angiography. He improved dramatically during the procedure as antegrade venous flow was re-established. Local thrombolytic therapy may be beneficial for other patients with rapid neurologic deterioration caused by extensive thrombosis of superficial and deep venous structures. PMID- 8198680 TI - Successful treatment of giggle incontinence with methylphenidate. PMID- 8198682 TI - Potential safety benefits of intelligent cruise control systems. AB - Potential safety impact of a hypothetical intelligent cruise control system (ICCS) is evaluated in terms of changes in traffic accidents and some traffic operation characteristics affecting safety. The analysis of changes in traffic accidents is accomplished by in-depth examinations of police accident reports for four major counties in California. The evaluation of changes in traffic operation characteristics affecting safety is accomplished by vehicle simulation. The accident analysis reveals that the use of the hypothetical ICCS could potentially reduce traffic accidents by up to 7.5%. Preliminary vehicle simulation results based on a 10-vehicle convoy indicate that the use of the hypothetical ICCS could reduce frequencies of hard acceleration and deceleration, enhance speed harmonization among vehicles, and reduce incidence of "less-safe" headway. PMID- 8198681 TI - Kynurenic acid is decreased in cerebrospinal fluid of patients with infantile spasms. AB - Cerebrospinal fluid (CSF) from 8 patients with symptomatic infantile spasms was collected before specific treatment for infantile spasms. The concentration of CSF kynurenic acid (KYA) and 3-hydroxykynurenine (3-OHKY) in infantile spasms was analyzed by high-performance liquid chromatography and compared with CSF KYA from 10 age-matched controls. The levels of CSF KYA were significantly lower in infantile spasm patients compared to controls (P < .05). In contrast, the levels of CSF 3-OHKY were significantly higher in infantile spasm patients than in controls (P < .05). These findings suggest that the presence of seizures in infantile spasms is associated with altered metabolism of 3-OHKY. The possibility that seizures may be related to increased or decreased production of certain kynurenine metabolites is discussed. PMID- 8198683 TI - Drink-driving law enforcement and the legal blood alcohol limit in New South Wales. AB - This paper reports the results of a preliminary analysis of daily fatal crashes in New South Wales, Australia, between July 1975 and December 1986. The analysis unexpectedly uncovered a small but statistically significant decline in crashes coinciding with the introduction of a law lowering the legal blood alcohol concentration (BAC) from .08 to .05 g%. The original aim of the analysis was to develop for a larger study appropriate log-linear techniques to assess the impact of a range of government initiatives, including laws aimed at the drinking driver: increased penalties, the .05 law, and random breath testing (RBT). The analysis showed that RBT immediately reduced fatal crashes by 19.5% overall and by 30% during holiday periods, and that the .05 law, introduced two years before RBT, apparently reduced fatal crashes by 13% on Saturdays. There was no significant effect of the .05 law on any other day of the week, and there was no clear evidence that any other initiative had a statistically significant effect on accidents. Although the apparent impact of the .05 law was small, it is surprising that any effect was discernible, since the law was not extensively advertised and police enforcement was no more intense than is usual over Christmas. However, any effects of the .05 law may not have been sustained if RBT had not been introduced two years later. PMID- 8198684 TI - Motorcycle crashes in New Zealand resulting in death and hospitalisation. I: Introduction methods and overview. AB - Relative to car crashes motorcycle crashes have received relatively little attention by the research community. This is the first in a series of three papers describing the epidemiology of motorcycle crashes resulting in death and hospitalisation in New Zealand. This paper describes the methods used for the study, provides an overview of all crashes, and, in particular, compares traffic crashes with nontraffic crashes. The source of the fatality data was national mortality data files for the years 1978 to 1987 inclusive. The source of the hospitalisation data was a national morbidity file, which records all public hospital discharges in New Zealand. A total of 1,175 motorcyclist fatalities were identified for the period 1978-1987, resulting in a mortality rate of 3.6 per 100,000 persons per year. A total of 2,623 motorcycle crash victims were hospitalised in 1988 resulting in a hospitalisation rate of 80.4 per 100,000 persons per year. Males, especially those 15-24 years of age had very high mortality (26-27) and morbidity rates (464-462). Motor vehicle traffic crashes represented 96% of the fatalities and 85% of the hospitalisations. Drivers were the victims in 88% of fatalities and 86% of hospitalisations. For hospitalised victims the leading injuries were to the lower limb (43%) and head (24%). Whereas 29% of the traffic crashes were AIS-3 or higher the comparable figure for nontraffic crashes was 19%. There has been a significant linear increase in the fatality rate between 1978 and 1988 but no comparable trend in hospitalisations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198685 TI - Motorcycle crashes resulting in death and hospitalisation. II: Traffic crashes. AB - This is the second paper in a series of three that describe the epidemiology of motorcycle crashes in New Zealand that result in death and hospitalisation. The first paper presented an overview of all motorcycle crashes. This paper focuses on traffic crashes. The source of the fatality data was national mortality data files for the years 1978 to 1987 inclusive. The source of the hospitalisation data was the 1988 national morbidity file which records all public hospital discharges in New Zealand. For the period 1978 to 1987, 1,175 fatalities were identified resulting in a mortality rate of 3.5 per 100,000 persons per year. Males aged 15-19 and 20-24 had very high rates (25.2 and 26.4, respectively), especially labourers (40.0) and forestry workers (32). Maori and non-Maori had similar rates. The majority (63%) of the deaths were attributable to a collision with another motor vehicle. During 1988 2,222 motorcyclists were hospitalised giving an incidence rate of 68.1 per 100,000 persons per year. Males aged 15-19 and 20-24 had very high rates (409 and 416, respectively), especially labourers (355). Maori had a higher morbidity rate than non-Maori (99 versus 61). The most common (40%) crash was a collision with another motor vehicle. The most common sites of injury were the lower limb (43%) and head (23%). Collision crashes were more likely to result in lower limb injury, be more severe, and result in longer stays in hospital. PMID- 8198686 TI - The effect of firm characteristics on truck accidents. AB - This paper expands an earlier analysis of the effect of firm characteristics and safety practices on truck accident rates. The sample size has been increased from 13,000 to 75,500. Negative binomial regressions are used in preference to the Poisson technique used previously. The current analysis confirms previous results, but provides important new insights into the safety implications of being a private carrier and hauling hazardous materials and the effect of having been in business for many years. PMID- 8198687 TI - Working on the hot seat: urban bus operators. AB - City bus operators suffer elevated health risks and striking levels of absenteeism and medical disability that may be related to occupational stress. This article provides a critical overview of findings on urban bus drivers' health status, paying particular attention to aspects of the physical and psychosocial job environment that may cause ill health. Methodological shortcomings in the research are discussed and preliminary ideas for salutagenic interventions are proposed. PMID- 8198688 TI - Psychosocial characteristics of alcohol-involved and nonalcohol-involved seriously injured drivers. AB - This study compared two groups of alcohol-positive and alcohol-negative, seriously injured, crash-involved drivers on demographics, personality characteristics, driving-related attitudes, prior driving history, lifestyle, substance use, and antecedent driver condition. The study sample was drawn from motor vehicle accident admissions to the Sunnybrook Health Science Centre Regional Trauma Unit. One hundred and six interviews were completed between August 1986 and November 1989, with blood alcohol concentration (BAC) data available for 96 drivers. These data suggest no driving-related attitude differences between the two groups. Self-reported driving histories indicated significantly fewer graduates of driving schools and more licence suspensions for the BAC-positive group. The only consistently significant differences were found for the drinking-related variables, with a greater percentage of the BAC-positive group reporting: lower age of first intoxication; a greater self-perceived drinking problem; a greater frequency of intoxication in the month before the accident; and greater self-reported drinking-driving in the month before the accident. Principal-components factor analysis revealed a four-factor solution labelled: Alcohol Use, Deviant/Illicit Drug Use, Aggression, and Neuroticism. Alcohol Use was the only factor found to contribute substantially to the discriminant function, together with the job-related stress item. These data suggest that seriously injured, alcohol-positive and alcohol-negative crashed drivers are similar except that the alcohol-positive drivers show more signs of an alcohol problem. PMID- 8198689 TI - Fatal injuries to restrained passenger car occupants in Canada: crash modes and kinematics of injury. AB - Passenger car collisions with other vehicles and with fixed objects were studied from a representative sample of fatal and injury-producing collisions collected according to a prescribed sampling plan. This paper describes our analysis of accidents involving restrained passenger car occupants who are fatally injured in collisions. Lateral collisions were found to be predominant, and both lateral and frontal collisions were associated with marked intrusion into the occupant compartment, causing direct, severe injuries to the head and chest of these occupants. Multiple severe injuries to more than one body region were common, and 90% of these victims died within one hour of the collision. The seat belt generally offered no protection to these fatally injured occupants. Reducing the incidence of fatal injury to properly restrained passenger car occupants will necessitate diminishing these very severe intrusion forces, especially from heavy trucks and fixed vertical hazards. For vehicle design modifications to be effective, it appears likely that roadway and roadside design and management must be included in the safety equation. Excessive speeds, inadequate traffic control, and unforgiving roadside hazards are playing a major role in the incidence of fatal injuries documented in this study. PMID- 8198690 TI - A comparison of hospital and police road injury data. AB - In order to gather as much information as possible on road crashes and outcomes, routinely collected police reports of traffic accidents and hospital discharge files were individually matched or "linked" using a computerised iterative procedure on name-identified data from both sources. The two groups of linked and unlinked hospital records were compared. Within the linked dataset, a comparison of like variables was made and showed good agreement between the two sources on accident type and road user type. However, police-reported levels of injury severity were shown to be less reliable. In addition, the proportion of hospital inpatient records that linked to a police record was found to be influenced by several factors. The overall linkage rate from hospital to police was 64% but varied from 29% for motorcyclists in single-vehicle accidents to 79% for motor vehicle drivers. The linkage rate increased with increasing levels of injury severity and was substantially lower for casualties of certain ethnic groups. It was deduced that for most instances where a hospital record did not link to a police record, the crash had not been reported. These findings confirm that there was considerable underreporting of hospitalised road casualties to the police and that the extent of underreporting was greater for those less severely injured. PMID- 8198691 TI - Training young cyclists to cope with dynamic traffic situations. AB - Two training methods were developed to teach young cyclists (8/9 years) how to behave in priority situations. One method was developed along the lines of the modelling principle. In earlier studies it was shown that this method is effective in teaching crossing strategies to young pedestrians. The other training method was based upon Anderson's Adaptive Control of Thought (ACT) theory, which describes the development of cognitive skills by proceduralisation and composition of behaviour and knowledge elements into automatic behaviour sequences. Two groups of children were trained with one of these methods. A control group did not receive traffic-related training in that period. The effect of the training was assessed by a knowledge test and a behaviour test. The results showed that the partly theoretical ACT approach initially resulted in an increased level of knowledge, which was found to have disappeared after a month. The modelling approach did not affect the level of knowledge. Both approaches had an equally positive effect on simple behavioural strategies, such as signalling and visual search behaviour. Correct application of priority rules appeared to be very difficult to teach. There was no effect of the two training methods. It seemed that children apply informal rules rather than formal rules when dealing with other traffic. It is hypothesized that these informal rules should form the starting point for training activities, because formal rules do not fit into children's cognitive framework of schemes, and therefore cannot be stored and retrieved effectively. PMID- 8198692 TI - Simulation of car impact to pedestrian lower extremity: influence of different car-front shapes and dummy parameters on test results. AB - Sled impact tests on mechanical substitutes for a pedestrian were conducted as a preliminary study for the purpose of developing a subsystem test procedure for the assessment of car-front aggressiveness to pedestrian legs. Four mechanical substitutes for a pedestrian were used in the test: the leg of a rotationally symmetrical pedestrian dummy (RSPD) as the representation of a subsystem, a HYBRID-II pedestrian dummy, a modified HYBRID-II pedestrian dummy equipped with a steel bar serving as knee joint, and a RSPD - HYBRID-IIP combined dummy in which the lower part of the RSPD and the upper part of the HYBRID-IIP were connected by a joint in such a way that the movements of the upper part were similar to those in cadaver tests. In the tests the following were evaluated: (i) the influence of vehicle shape on knee response and on vehicle impact force; (ii) the influence of the upper body mass on knee response and on vehicle impact forces; (iii) the influence of the bumper system on knee response, the kinematics of pedestrian mechanical substitute, and on vehicle impact forces; (iv) the influence of pedestrian mechanical substitute characteristics on its kinematics and knee response, and on vehicle impact forces. This paper describes a primary concept when subsystem test methods for the assessment of car-front aggressiveness to pedestrian legs in a car-pedestrian collision are considered. PMID- 8198693 TI - Responsibility analysis: a methodology to study the effects of drugs in driving. AB - In order to study the role of drugs in driving, a responsibility analysis was developed to allow an assessment to be made of the driver's culpability or responsibility in an accident. Factors possibly mitigating drivers' responsibility in each accident were identified and scored. Factors considered were: condition of road, condition of vehicle, driving conditions, accident type, witness observations, road law obedience, difficulty of task, and level of fatigue. If a sufficient number of mitigating factors were identified a driver would be found to be either partly or totally exonerated from blameworthiness and scored either as a contributory or nonculpable driver. If drugs present in a driver contributed to accident causation, it would be expected that they would be overrepresented in culpable drivers, i.e. those drivers not exonerated from blame. A total of 341 driver fatalities occurring in Victoria were analysed for blood alcohol content (BAC). Twenty-nine percent had a BAC over .05% (the legal limit in Victoria). Alcohol-positive drivers were statistically overrepresented in the culpable group (p < .001), in single-vehicle accidents (p < .05) and those accidents in which vehicles left the road for no apparent reason (p < .001). Odds ratio estimation of relative risk of culpable and nonculpable drivers showed that the relative risk rose disproportionately to BAC. PMID- 8198694 TI - Seat-belt wearing and driving behavior: an instrumented-vehicle study. AB - Less-than-expected fatality reductions after seat-belt legislation has been introduced in a jurisdiction may be explained in terms of selective recruitment of parts of the driving population and/or behavioral adaptation by beginning belt users. The present investigation has compared the relative merits of these two hypotheses at the level of individual driver behavior. In the initial study the driving behavior of groups of habitual wearers and nonwearers of the belt was compared. Nonwearers made two trips, one with the belt on and one without the belt. Habitual wearers drove belted only. The main part of the experiment was a 105 km freeway route. Two additional tasks of a somewhat more critical nature, a double lane-change manoeuvre and the performance of a braking manoeuvre in front of a fixed obstacle, were performed after the freeway trips. Factor analysis on 39 variables describing driving behavior on the road and during the additional tasks resulted in five factors. One of these, the factor describing the distribution of driving speed on the freeway, differentiated between nonwearers and wearers (thus yielding support for the selective recruitment hypothesis) as well as between wearing and not wearing the belt by the same drivers (thus yielding support for the behavioral adaptation hypothesis). In the follow-up study the original wearers and nonwearers were assigned to one of four experimental treatments: (i) the promise by the experimenter of a considerable incentive for not having a culpable motor vehicle accident over a period of a year. Half the habitual wearer subjects were assigned to this condition. The expectation was that this group would become more careful in their driving; (ii) a control group, consisting of the remaining habitual wearers; (iii) the agreement between the experimenter and the subject that the latter would buckle up in everyday driving for the year to come--half the habitual nonwearer subjects were assigned to this condition; (iv) a control group to the previous treatment, consisting of the remaining habitual nonwearers. All subjects returned for repeat measurements, consisting of the freeway trips plus additional tasks, three times over the next year. The main result was that beginning wearers (group iii) showed signs of continuing behavioral adaptation, in the form of increased speed and increased propensity for close following, as well as several minor effects. The "incentive" group (group i), however, did not change driving behavior in the expected sense, i.e. in the safe direction. PMID- 8198695 TI - Estimating overinvolvement of seat belt nonwearers in crashes and the effect of lap/shoulder restraint use on different crash severity consequences. AB - At least some of the controversy surrounding the level of effectiveness of seat belts has arisen due to the difficulty in calculating a direct impact on police reported accident data. These data are notoriously biased in the direction of belt-wearing overestimation. Furthermore, not enough information on nonwearer overrepresentation in crash involvement is currently available over the entire range of accident severity levels. The work reported in this paper was undertaken in order to develop a methodology for calculating nonwearer overrepresentation at various levels of crash severity and for adjusting police-reported belt-wearing data. The underlying premise was that police officers make reasonably consistent and valid judgements related to probable fault or causor status in casualty producing accidents that they attend. Separating reported wearer and nonwearer crash involvements into culpable and nonculpable situations led to a procedure for adjusting police-reported belt-wearing totals to account for likely overestimation and also enabled the assessment of probable levels of nonwearer overrepresentation in crashes at all severity levels. The results, in terms of both nonwearer overrepresentation and seat belt effectiveness, were comparable with those reported in the literature for fatal crash involvement. Seat belt effectiveness was found to average 49% for fatal crashes, 35% for serious-injury crashes, 18% for moderate-injury crashes, and 11% for minor-injury crashes. Belt nonwearer overrepresentation was found to increase with increasing levels of belt wearing in the driver population from a factor of between 2 and 5 (depending on crash severity) at b = 0.5 to between 5 and 10 as b approached 0.9. PMID- 8198696 TI - Cross-reactivity of IgG and IgM secreting B cells in normal and autoimmune mice. AB - Antibodies from animals with lupus react with a diverse array of foreign and self antigens. This has been attributed to the activation of large numbers of mono specific B cells, although it could result from the stimulation of a smaller population of highly cross-reactive lymphocytes. To examine this issue, a chamber ELIspot assay was used to compare the cross-reactivity of Ig-secreting B cells from autoimmune vs normal mice. The cross-reactivity of IgM-secreting lymphocytes was significantly greater than that of IgG-secreting cells in normal BALB/c and DBA/2 mice. For example, 5-23% of IgM but only 0.1%-0.4% of cells secreting IgG antibodies against DNA or TNP-BSA were cross-reactive. When normal animals were immunized and boosted with TNP-KLH, the resultant IgG anti-TNP response was essentially mono-specific. There was no significant difference in the proportion of lymphocytes producing cross-reactive IgM antibodies in normal vs autoimmune mice. In contrast, the frequency of cross-reactive IgG-secreting B cells in lupus prone MRL-lpr/lpr and (NZB x NZW)F1 animals was at least 15 times higher than in normal mice. These observations indicate that the repertoire of IgG-secreting cells in active lupus differs qualitatively from that seen spontaneously or following antigenic stimulation in normal animals. PMID- 8198697 TI - Eukaryotic expression of recombinant human centromere autoantigen and its use in a novel ELISA for diagnosis of CREST syndrome. AB - The cDNA coding for the human full-length centromere protein B (CENP-B) was isolated from a liver cDNA library by oligonucleotide screening and extended at the 5' and 3' ends by linker addition. The cDNA was inserted into a modified baculovirus transfer vector which mediated high-level expression of recombinant human CENP-B with a histidine-hexapeptide as affinity ligand at its N-terminus in infected Spodoptera frugiperda (Sf9) insect cells. Based on the histidine hexapeptide moiety, the recombinant CENP-B was purified to homogeneity by single step affinity chromatography using metal chelating matrix. An ELISA established with the eukaryotically expressed and purified recombinant human full-length CENP B demonstrated its excellent specificity, sensitivity and reproducibility for the measurement of autoantibodies directed to the human CENP-B (ACA-B) representing a diagnostic marker for CREST syndrome, an autoimmune rheumatic disease. In this study, all pathological sera from patients (n = 80) with serologically and clinically diagnosed CREST were positively assayed for ACA-B, whereas 399 sera obtained from blood donors and 82 out of 84 sera from patients with autoimmune rheumatic disorders which were unrelated to CREST were negative in the ELISA. PMID- 8198698 TI - Genetically determined target organ susceptibility in the pathogenesis of spontaneous autoimmune thyroiditis: aberrant expression of MHC-class II antigens and the possible role of virus. AB - Considerable controversy exists concerning the role of aberrant MHC-class II antigen expression in the pathogenesis of organ-specific auto-immune disease. Since Obese strain (OS) chickens are afflicted with a spontaneously occurring autoimmune thyroiditis (SAT), we have readdressed this pivotal question by investigating the chronical appearance of MHC-class II antigens on thyroid epithelial cells (TEC) of OS and normal healthy CB chickens before onset of overt clinical symptoms in the former. Among the candidates as potent inducers of aberrant MHC-class II antigen expression, interest in our studies focussed on the potential role of viruses in the development of SAT. Since aberrant MHC-class II antigen expression could prove to be an epiphenomenon of virally afflicted TEC, we determined 2,5-oligoadenylate synthetase and 2,5-oligoadenylatepolymer cytosol levels in both chicken lines. Our results indicate that the presence of infiltrating lymphocytes does not necessarily represent a prerequisite for the aberrant expression of MHC-class II antigens but coincides in most cases. However, the phenomenon seems to play a perpetuating rather than a causative role. Moreover, in support of a possible viral involvement, elevated levels of the 2,5-oligoadenylate synthetase and 2,5-oligomers could be demonstrated in TEC cytosol of OS chickens. PMID- 8198699 TI - Golgi autoantibodies and autoantigens. AB - Autoantibodies directed against cellular constituents rarely react with antigens localized in the Golgi apparatus and little information is available regarding these particular antibodies. Although thousands of samples have been examined for autoantibodies in our laboratory on a routine basis, only three human sera with anti-Golgi antibodies could be studied. Using pre-embedding immunoelectron microscopy we have demonstrated that these sera have antibodies reacting with antigens located in the Golgi apparatus. The reaction product was exclusively located on cisternal and vesicular Golgi membranes. No intraluminal staining was seen and some saccules were negative. No specificity for a peculiar tissue or cell line was noted, suggesting that the targets or these autoantibodies are evolutionarily conserved. The F(ab')2 fragments retained full binding capacity in indirect immunofluorescence experiments, confirming true antibody activity. When tested by immunoblotting, the three sera reacted with different antigens with relative molecular weights of respectively 230, 150 and 80 kDa. The antigens recognized by anti-Golgi antibodies in two of the three sera were insensitive to trypsin degradation. Together, these results suggest that a set of different autoantigens are recognized by sera from various patients. PMID- 8198700 TI - Treatment with antibody reactive with the nephritogenic idiotype, IdLNF1, suppresses its production and leads to prolonged survival of (NZB x SWR)F1 mice. AB - The F1 progeny of the cross between SWR and NZB mice (SNF1) develop severe immune complex glomerulonephritis, similar to that seen in human SLE. An idiotypically related family of nephritic antibodies (IdLNF1) has been shown to be important in the pathogenesis of autoimmune glomerulonephritis in these mice. Interestingly, the majority of IdLNF1+ antibodies do not bind DNA. Here, we sought to examine whether regulation of the expression of this idiotype was important in the development of lupus nephritis and to identify the mechanisms regulating its expression. In the present study, biweekly injections of SNF1 mice with 100 micrograms of rabbit anti-IdLNF1 antibodies, beginning at 8 to 10 weeks of age, resulted in significant P < or = 0.05) suppression of IdLNF1+ Ig(G+M) and IgG production. The decrease appeared to be mediated via significant (P < or = 0.05) decreases in the percentage of IdLNF1-expressing B cells and CD4+ IdLNF1-specific T cells in the treated SNF1 mice compared to the controls. This was accompanied by a significant (P < or = 0.005) increase in survival with delayed onset of glomerulonephritis. Surprisingly, there was no difference in the incidence of anti-DNA antibody production between the treated and control SNF1 mice. These results support the hypothesis that dysregulation of pathogenic idiotypes, not confined to anti-DNA antibody idiotypes as had been shown in previous studies, may contribute to the development of SLE. PMID- 8198701 TI - Heterogeneous IgG subclass distribution of islet cell antibodies. AB - Islet cell antibodies (ICA)-IgG are the serological marker of type 1 diabetes, an organ-specific autoimmune disease. A proportion of patients also have thyro gastric autoimmunity, implying a broader humoral autoreactivity in these cases. In order to determine whether this is also reflected within islet cell antibodies (ICA) we examined the ICA-IgG subclass distribution in type 1 diabetic patients with or without associated thyro-gastric autoantibodies. ICA-IgG subclasses were detected by two-step indirect immunofluorescence, using monoclonal antibodies against the four IgG subclasses, in sera from 51 patients with type 1 diabetes and detectable ICA; 31 had no other antibodies (group 1) and 20 had at least one associated thyroid and/or gastric autoantibody (group 2). Our results show that ICA are polyclonal and invariably IgG1. In 48% of patients with type 1 diabetes without associated thyro-gastric autoantibodies, ICA were restricted to IgG1 only. Conversely, only 10% of those with thyro-gastric antibodies had ICA-IgG1 only (P < 0.02), and a larger ICA-IgG subclass recruitment was observed in these patients (P = 0.002). These findings provide evidence of heterogeneity within ICA at the IgG subclass level, with a broader clonal recruitment within this specificity in individuals displaying features of multiple organ autoimmunity. These results support the hypothesis of heterogeneity within the pathogenetic process leading to type 1 diabetes. PMID- 8198702 TI - Antibodies to glutamic acid decarboxylase in at-risk and clinical insulin dependent diabetic subjects: relationship to age, sex and islet cell antibody status, and temporal profile. AB - Antibodies to glutamic decarboxylase (GADAb) are present in insulin-dependent diabetes (IDD) but their association with age and sex and their temporal profile in relation to disease onset have not been fully documented. We have examined the association between GADAb and islet cell antibodies (ICA), age and sex, and have cross-sectionally and longitudinally measured the levels of GADAb before and after diagnosis of IDD. GADAb were measured by allowing serum immunoglobulin prebound to protein A Sepharose to precipitate GAD enzymatic activity from a fetal pig brain extract. GADAb levels were above the normal range (mean + 3SD of healthy controls, 460 nU/ml) in 19/44 (43%) at-risk subjects (ICA positive first degree relatives of persons with IDD), 35/108 (32%) recent-onset IDD subjects and 22/46 (47%) established IDD subjects. When analysed according to age and sex, GADAb levels were significantly higher (P < 0.05) in post-pubertal females in at risk, recent-onset and established IDD groups. There was a significant association between GADAb and ICA > 20 in both first degree relatives (P < 0.001) and recent-onset subjects (P < 0.01) and GADAb were uncommon in the absence of ICA. Levels of GADAb were similar in at-risk, recent-onset and established IDD subjects and GADAb status remained stable in all but 2/41 at-risk subjects followed for 17 (mean, range 3-33) months. In conclusion, GADAb levels are strongly influenced by age, sex and ICA status, and generally remain stable in at risk subjects and after the onset of clinical IDD. PMID- 8198704 TI - Detection of autoantibodies to Ro(SS-A), La(SS-B) and U1RNP in different congenital heart rhythm disorders using immunoblot and enzyme immunoassay. AB - The aim of the study was to determine if autoantibodies have distinctive qualitative or quantitative characteristics in children with congenital heart rhythm disorders compared to unaffected infants. Sera of fifty-three infants with different heart rhythm disorders and eight unaffected children born to SLE mothers were tested for antibodies to Ro(SS-A), La(SS-B) and U1RNP (including recombinant A-, C-, 68 kD-proteins) using enzyme immunoassays and immunoblot. 21 sera from affected and 8 sera from healthy children reacted in counter immunoelectrophoresis with Ro(SS-A). 8/8 infants with third degree atrioventricular (AV)-block, 4/8 with first degree AV-block, one with sinusbradyarrhythmia (SB) and another with SB/first degree AV-block were anti-52 kD Ro(SS-A) positive compared to 7/8 healthy infants. Infants with third degree AV-block had significantly higher anti-52 kD Ro(SS-A) levels than those with the milder heart rhythm disorders (P < 0.01) and the healthy group (P < 0.002). Anti La(SS-B) antibodies were detected significantly (P < 0.01) and in significantly higher titres (P < 0.01) in AV III than in other types of congenital heart block. Anti-U1RNP-68 kD antibodies were positive in 3/8 healthy, 2/8 first degree AV block and in 1/8 third degree AV-block cases. Third degree AV-block was more frequently found in female infants (P < 0.05). It was concluded that the influence of antibody levels to the 52 kD Ro(SS-A) and La(SS-B) components and the association of anti-52 kD Ro(SS-A), La(SS-B) and -60 kD Ro(SS-A) antibodies, as well as the sex, on the severity of congenital AV-conduction defects suggests involvement of these factors in the pathogenesis of these disorders. PMID- 8198703 TI - Macrogolgin--a new 376 kD Golgi complex outer membrane protein as target of antibodies in patients with rheumatic diseases and HIV infections. AB - Antibodies against the Golgi complex (GC) were found by indirect immunofluorescence microscopy in the serum of two patients with sclerodermia and Sjogren syndrome. Serum from one patient was used to screen clones from an oligo (dT) primed HeLa cDNA expression library. Four overlapping cross hybridizing clones (G1, G12, G13, G14) were found. One additional 5' clone (G15) was retrieved from a random primed lambda gt11 human thyroid cDNA library by nucleic acid hybridization, exploiting sequence information of clone G12. Additional clones for both the 5' and 3' ends were generated by RF-PCR from HeLa cell mRNA. Alignment of the overlapping clones resulted in a consensus cDNA of 10,300 bp encoding a protein of 376 kD. A corresponding mRNA of about 10 kb was found in Northern blots of RNA from various cultured cells. The most distinct features of the protein were the extraordinarily high fraction of alpha-helical domains containing heptad repeats with the probability of forming coiled-coils and the structure similarities with the myosin family and the yeast intracellular transport protein USO1. Five overlapping cDNA fragments covering the entire open reading frame were used to synthesize recombinant proteins for affinity purification of the antibodies in the two patients' sera. By use of these affinity purified antibodies, staining of the GC of various cultured cell lines was reproduced. The antibody target was dissociated within 15 min after brefeldin A exposure of cultured cells, a phenomenon, which was fully reversible within 30 min after withdrawal of the drug. Sucrose step gradient separation of GC enriched microsomal fractions from rat liver showed a natural antigen of about 380 kD co fractionating with the GC marker galactosyltransferase. KCl extraction, Triton X 114 partition, as well as trypsin digestion of microsomal fractions revealed that the hydrophilic protein has to be located on the cytoplasmatic surface of GC vesicles. Using the five blotted recombinant protein fragments, anti-GC antibodies were found in 18 of 164 (11%) HIV positive patients but in none of the 64 healthy controls. HIV patients as well as the two original patients showed a diverse antibody spectrum recognizing different epitopes of the recombinant proteins. The protein characterized herein, for which we propose the provisional name macrogolgin, constitutes the largest protein known so far associated with the GC. PMID- 8198705 TI - Bcl-3-mediated nuclear regulation of the NF-kappa B trans-activating factor. AB - The NF-kappa B factor governs the expression of many genes encoding immunoregulatory molecules. This activity is itself controlled. In this article, novel nuclear pathways for NF-kappa B regulation are described. PMID- 8198706 TI - Inadequate epidermal homing leads to tissue damage in human cutaneous leishmaniasis. AB - Leishmaniasis is a model disease for the study of immunoregulatory mechanisms associated with host resistance and susceptibility. In this article, Felix Tapia and colleagues propose that defects in the signaling properties of the epidermis can result in the generation of either a chronic granulomatous response, which is unable to eliminate the parasite, or a proinflammatory mucocutaneous response and tissue damage. PMID- 8198707 TI - IgM hexamers? AB - There has been a universal tendency to regard IgM antibodies as pentameric molecules comprising five immunoglobulin monomeric subunits joined by a single J chain protein. Is this the only form of secreted IgM, or are the possibilities more complex? In this article, Joseph Brewer and colleagues propose that the IgM polymers secreted in primary immune responses may be more heterogeneous than previously believed and that, as a consequence, the biological activity of IgM may have considerable flexibility. PMID- 8198708 TI - The interleukin-8-receptor family: from chemokines to malaria. AB - The interleukin 8 (IL-8)-receptor family includes two specific receptors (type A and B) that both bind IL-8 with high affinity. These receptors have been cloned, and belong to a superfamily of G-protein-linked receptors that signal in response to IL-8 on a variety of cell types. In contrast to these receptors, which have a narrow ligand-binding profile, a promiscuous IL-8 receptor has been found on human erythrocytes that binds a variety of chemokines with high affinity. This protein, known as the chemokine receptor, was recently shown to bind the malarial parasite Plasmodium vivax, and may play a major role in inflammation by limiting the concentration of soluble chemokines in the circulation. PMID- 8198709 TI - Immune surveillance and sunlight-induced skin cancer. AB - Immune surveillance poses the existence of a recirculating pool of lymphocytes that migrate randomly through somatic tissues. Upon recognition of neoantigens on malignantly transformed cells, lymphocytes proceed to attack and destroy degenerate cells before a tumor emerges. Here, J. Wayne Streilein and colleagues review the effects of ultraviolet B irradiation on the induction of cutaneous immunity in the skin of mice and humans. Furthermore, they discuss the possibility of a genetic predisposition to skin cancer, mediated by a defect in the normal process by which contact hypersensitivity, and therefore immunogenicity, is elicited. PMID- 8198711 TI - On the generation of diversity in endogenous superantigens. PMID- 8198710 TI - Superantigens and retroviral infection: insights from mouse mammary tumor virus. AB - Superantigens induce a vigorous immune response by stimulating T cells that express particular T-cell receptor V beta chains. Mouse mammary tumor virus is a milk-transmitted retrovirus that encodes such a superantigen. Paradoxically, as discussed by Werner Held and colleagues, the strong superantigen-induced immune response permits the survival of the virus via T-cell dependent clonal expansion of infected B cells. PMID- 8198712 TI - Declining incidence of paediatric burns in Scotland: a review of 1114 children with burns treated as inpatients and outpatients in a regional centre. AB - This retrospective study of paediatric burns in the Lothian region involved a review of 1114 case notes of children up to the age of 12 years, treated for burns as inpatients and outpatients, during a 3-year period between 1988 and 1990. There were more boys than girls and 79 per cent were below 5 years of age. 71.5 per cent were treated as outpatients only, whereas 28.5 per cent were admitted. The Lothian region had the highest incidence of burns of children in Scotland. There has been a statistically significant downward linear trend in burn rates and admissions in Scotland during the 20 years but in this hospital burns admissions have significantly diminished only since 1987. The number of flame burns has declined and a high proportion of the victims were scalded. Efforts need to be made to reduce the large number of scalds by educational and legislative measures. PMID- 8198713 TI - Scald burns in children caused by hot drinks--the importance of the type of cup. AB - A prospective study of 36 consecutive scald injuries in children caused by hot beverages is reported. Almost a third of these were deep dermal or full skin thickness and the highest percentage resulted in injury to the upper chest region. The study further investigates the cooling characteristics in four different types of cup. These studies clearly show the potential for significant disfigurement from this type of injury for up to 11 min from the time the drink is poured. The need for greater public awareness in relation to hot drinks is highlighted. PMID- 8198714 TI - Effects of argon beam coagulation on split thickness skin graft survival in the swine model. AB - Argon beam coagulation (ABC) uses argon gas to evacuate blood in an operative field and simultaneously to transport a coagulating electric current to bleeding sites. This allows a 'no touch' method of coagulation which is faster, more precise, and less destructive than conventional electrocautery. The technique has been used to reduce blood loss in liver surgery, trauma surgery and neck dissections. In this study, the effect of ABC treatment of the recipient graft beds on the survival of split thickness skin grafts was assessed in pigs, testing the hypothesis that ABC treatment of the recipient bed would have no adverse effect on skin graft survival. Nine 20 kg mixed breed pigs had split thickness skin grafts raised on each side of the paraspinous area. The graft beds on one side were prepared using ABC and the contralateral side served as controls. The percentage of graft survival on the ABC treated sides was compared to control graft survival on the other side at 12 days postsurgery. Our results confirm the hypothesis that treatment of the recipient bed with ABC does not adversely affect the survival of split thickness skin grafts. PMID- 8198715 TI - Altered biosynthesis of tumour necrosis factor (TNF) alpha is involved in postburn hypertrophic scars. AB - The present study shows that the decrease of TNF alpha in postburn hypertrophic scars is due to a decrease in the steady-state level of TNF alpha mRNA and thus to an altered biosynthesis of the cytokine. Thirteen scars, including seven hypertrophic and six normotrophic scars, were tested for TNF alpha mRNA production by a semiquantitative reverse polymerase chain reaction (PCR) method. TNF beta and beta actin were tested as a control. Six out of six normotrophic scar samples amplified with primers for TNF alpha showed a positive PCR signal up to the 1:32 dilution. On the contrary all the hypertrophic tested samples (7/7) had a positive PCR signal only at the 1:1 or 1:2 dilution. All samples, both normotrophic and hypertrophic, were homogeneous as to TNF beta production. PMID- 8198716 TI - Dynamic changes of fibrinopeptides A and B in sera of burn patients and their effects on vascular endothelial cells. AB - In this study, dynamic changes of fibrinopeptides A and B (FPA, FPB) in sera of burns patients are determined with an HPLC method. On this basis detrimental effects of FPA and FPB on vascular endothelial cells (VEC) are observed in vitro. The main results are as follows: (1) FPA and FPB in 18 burn patients' sera increase at day 2 postburn, reach peaks at days 5-7 postburn, then decline after day 15 postburn, and return to the control levels at day 25 postburn. The fluctuations in FPA and FPB levels in burn patients' sera are parallel to the progress of burn illness. The measurements of FPA and FPB levels in burn patients' sera may be useful in evaluating patients' condition. (2) FPA and FPB are detrimental to the cultured VEC in vitro. Characteristics of their injurious effects are: specific, irreversible and dose dependent. FPA and FPB may play an important role in endothelial injury. PMID- 8198717 TI - Effect of PGE in multiple experimental models. IX: In vivo effects of PGE on immune response of leucocytes to wounds. AB - There have been conflicting results obtained when comparing the in vitro with in vivo effects of prostaglandin E (PGE) on immune function. The in vitro studies have demonstrated immune suppression with PGE administration while the in vivo studies demonstrated improved survival when utilizing infected models. To attempt to resolve this discrepancy, we evaluated the in vivo effect of PGE on host immune function utilizing multiple rat models. PGE was found to have no effect on the ability of leucocytes to infiltrate a sponge matrix wound over a 2-week period of study. PGE also failed to alter the percentage of T-lymphocyte subset populations infiltrating the sponge matrix model. There was noted to be no effect of PGE on the ability of neutrophils to chemiluminescence, or on metabolic function of lymphocytes. In conclusion, PGE does not appear to have immunosuppressive properties when studied using certain in vivo models. PMID- 8198718 TI - Multivariate and vectorial analysis of pharmacological signalling: diaphragm inositol 1,4,5-triphosphate under the duress of burn trauma. AB - Aberrant signal transduction processes within the diaphragm contribute to the weakness of this primary muscle involved in respiration. The importance of this report emphasizes how scald burn injury manifests distant systemic effects which impact on respiration. Scald burn injury from hot water is a common type of thermal injury in three specific patient groups: young children, the elderly, and the mentally and physically handicapped. Multivariate and vectorial analyses are presented within this paper with application to the effects of burn trauma on pharmacological signal transduction systems in the diaphragm. Multivariate equations showed the dependence of IP, on three to five independent variables. The independent variables included: burn size, glycerophosphate, and other polyinositols (inositol 1,4 biphosphate (I1,4P2), inositol 1 phosphate (I1P) and inositol). Graphic illustration of the equations used vectorial analysis. The multivariate analysis gives rise to a wider class of contributing factors than those observed using standard univariate relationships. This may be useful clinically in the identification of therapeutic agents for the treatment of respiratory problems in burn patients. PMID- 8198719 TI - Comparative study of split thickness skin grafts taken from the scalp and thigh in children. AB - We compared 29 split thickness skin grafts taken from the thigh (group I) and 37 taken from the scalp (group II). The study was prospective with a follow-up period of 1 year. The average age was 29 months. Included in group I were those children whose parents refused permission for their hair to be shaved and those with burns to the head. We compared ease of technique, percentage of graft accepted, quality of the graft and after-effects of the donor site. Acceptance of the graft was close to 100 per cent in both groups. Harvesting was more difficult from the scalp (P < 0.0001). The quality of the grafts was identical in both groups. After-effects at the donor site were absent in group II and evident in group I (P < 0.0001). There was no alopecia. The scalp represented a better donor site for split-thickness skin grafting than the thigh in the child. PMID- 8198720 TI - An easy way to prepare microskin grafts. AB - The conventional technique to produce microskin grafts is a relatively time consuming procedure. We developed an easy method by using a trimmed circular dermacarrier with the non-grooved side up and driving forward in the meshgraft instrument through six different angles that were 30 degrees apart. The tiny skin particles obtained by this method not only saved operation time but also survived well in the grafted wounds. PMID- 8198721 TI - Paediatric burns in Bucharest, Romania; 4327 cases over a 5-year period. AB - This is a retrospective study based upon 4327 paediatric burns (0-16 years of age) admitted over a period of 5 years, as from January 1988. Epidemiological data include age, sex, cause of burn, extent of injury, social and economic status, period of time between the accident and the admission to hospital. The overall mortality rate was 5.8 per cent. We tried to correlate the mortality rate with the epidemiological data. The recent use of Flamazine cream in our centre (as from January, 1993) seems to have decreased the mortality rate to 2.6 per cent (12 deaths out of 450 patients admitted during the first 7 months of 1993). No study of childhood burns has previously been reported from Romania. PMID- 8198722 TI - Comparison of high-frequency jet to conventional mechanical ventilation in the treatment of severe smoke inhalation injury. AB - The pathophysiology of smoke inhalation includes surfactant inhibition and pulmonary vascular injury leading to a high permeability pulmonary oedema. It has been shown in surfactant deficient animal models that methods of ventilation (i.e. high-frequency ventilation - HFV) avoiding a large pressure excursion (i.e. pressure change from end expiration to peak inspiration) improves oxygenation and decreases hyaline membrane formation. Therefore, we compared HFV with conventional mechanical ventilation (CMV) on lung function in an acute animal model of smoke inhalation (SI). Mongrel dogs were anaesthetized, surgically prepared for haemodynamic and blood gas monitoring, and placed on either CMV (n = 6) or HFV (n = 7). Following baseline (BL) measurements both groups were ventilated with wood smoke for 10 min. Ventilator settings were not adjusted from baseline following smoke inhalation in either groups; positive and expiratory pressure (PEEP, approximately 6 mmHg) was added in both groups following smoke exposure. At the conclusion of the study (4 h postsmoke inhalation) lung samples were taken for surfactant function and lung water measurements. Smoke inhalation immediately increased the A-a gradient (CMV-BL = 6.9 +/- 2.4 to CMV-SI = 77.3 +/- 1.9; HFV-BL = 10.5 +/- 2.7; HFV-SI = 72.8 +/- 3.7 mmHg), venous admixture (CMV-BL = 6.9 +/- 2.8 to CMV-SI 69.8 +/- 6.6; HFV-BL = 7 +/- 1.7 to HFV-SI = 60.4 +/- 7.9 per cent) and decreased Pao2 (CMV-BL = 110 +/- 3.4 to CMV-SI = 28 +/- 3.5; HFV-BL = 103 +/- 3.6 to HFV-SI = 31 +/- 1.7 mmHg) to a similar level in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198723 TI - Cica-Care gel sheeting in the management of hypertrophic scarring. AB - A prospective, controlled clinical trial was undertaken to assess the efficacy and safety of two types of silicone gel, Silastic Gel Sheeting (SGS) and Cica Care (CC), in the management of hypertrophic scars. Forty-two patients were randomly assigned to SGS and CC groups and their hypertrophic scars were divided into treated and control areas. Extensometric measurements were made at monthly intervals for 6 months and significant improvement of the treated areas relative to the control areas was observed. The two gels were not significantly different in efficacy or safety, but CC, being more adhesive and more comfortable than SGS, has advantages in ease of use and patient acceptability. PMID- 8198724 TI - Treatment of skin defects using suspensions of in vitro cultured keratinocytes. AB - The in vitro cultivation of keratinocytes and their application in the form of confluent sheets to cover various kinds of skin defects involves a number of problematical steps which could be improved by using single cell suspensions instead. Therefore we developed a method to apply keratinocytes suspended as single cells in a fibrin gel. By testing the feasibility of this method in different experimental animal models we found that it facilitates cultivation as well as application of the cells, moreover, this method allows a much more flexible use of the cells, i.e. it is easier to consider the clinical condition of the patient than by the conventional method. PMID- 8198725 TI - A comparative analysis of burn injuries at two burns centres in Denmark. AB - In order to compare the epidemiology of burns and predisposing factors to burns at two burn centres representing the cities of Aarhus and Copenhagen, Denmark, a prospective study was set up at the University Department of Orthopedic Surgery and Traumatology, Aarhus and the Centre of Plastic Surgery and Burns Unit, Hvidovre Hospital, Denmark. Several significant differences in the epidemiology of burns in the two populations were found. Considering the social circumstances, the situation in Aarhus was characterized by the fact that most patients lived in their own houses, had a larger family and a larger family income. At the Hvidovre Hospital, the patients more often lived in a flat, had a smaller family and a lower family income than the average. PMID- 8198727 TI - Spontaneous pneumothorax in association with a major burn. AB - We report a case of a spontaneous pneumothorax in association with a major burn. The pneumothorax remained undetected for 4 days and the patient underwent a 2 h aeromedical transfer which could potentially have been hazardous. We strongly recommend that arterial blood gas analysis is performed before air transport of moderate or severely burned patients. If blood gases are abnormal a chest X-ray should also be performed. In practice a strong case can be made for routinely obtaining a chest X-ray in these patients. In-flight monitoring should include pulse oximetry. PMID- 8198726 TI - The use of recombinant human erythropoietin and cultured epithelial autografts in a Jehovah's Witness with a major thermal injury. AB - Haemostatic debridement, recombinant-human erythropoietin and cultured epithelial autografts have been used successfully in a Jehovah's Witness with a major burn injury. Tourniquet ischaemia complemented by a topical haemostatic agent minimized excisional blood loss, while recombinant-human erythropoietin accelerated erythropoiesis, thereby correcting postburn anaemia. Cultured epithelial autografts provided coverage of the granulating wounds without creating donor sites. PMID- 8198729 TI - Recent references. Burns. PMID- 8198728 TI - Toxic shock syndrome associated with use of Biobrane in a scald burn victim. AB - Biobrane remains an excellent biosynthetic dressing for thermal injury coverage. The present report of a probable case of toxic shock syndrome associated with its use does not question its efficacy as temporary coverage for partial thickness thermal burns. Instead, attention is focused on raising the index of suspicion of toxic shock syndrome in burn patients treated with Biobrane, or other occlusive dressings, who develop early signs or symptoms which may be consistent with the diagnosis. PMID- 8198730 TI - Protein C and protein S levels in some burn patients. PMID- 8198731 TI - Alternative homograft skin sources. PMID- 8198732 TI - Burn treated with ethyl alcohol. PMID- 8198733 TI - Trace element (Al, Se, Zn, Cu) levels in serum, urine and tissues of burn patients. AB - Trace elements are known to play many important roles in humans. It has also been shown that some of these elements are essential in wound healing. In this study, aluminium, copper, zinc and selenium levels were determined in serum, urine and tissue samples of burned patients and the relationships between wound healing and trace elements were evaluated. Trace element levels were determined using atomic absorption spectrophotometry. During 20 days' treatment, a significant rise in aluminium levels was determined in serum, urine and tissue samples of patients. After day 5 of treatment, copper levels increased significantly only in urine samples. Zinc levels decreased in serum and tissue samples. However, zinc gave high values in urine within the first week then returned to the initial value. There was a significant decrease in zinc in serum and tissue samples taken from burned patients during treatment. Urine selenium levels showed a significant rise within the first 15 days. PMID- 8198734 TI - Long-term results of treatment of scalds in children with glycerol-preserved allografts. AB - A retrospective study followed by a clinical examination was carried out 2-5 years postburn to analyse the long-term results of the treatment of scalds in children (n = 45) with glycerol-preserved allografts. In 21 patients (47 per cent), the wounds healed spontaneously. In 24 patients, remaining defects were closed by a split skin autograft in the third week postburn. Healing without scar formation was seen in 24 patients (53 per cent), 9 patients (21 per cent) showed moderate, and 12 patients (26 per cent) severe scar formation. Transplanted areas showed hyperpigmentation, and donor sites depigmentation. The cosmetic results require further improvement, and classification of present and new methods of treatment. Clinical research is limited by the number of observations and the great variation in wounds. A well-standardized experimental animal model is, therefore, essential. PMID- 8198735 TI - Reduction in Staphylococcus aureus wound colonization using nasal mupirocin and selective decontamination of the digestive tract in extensive burns. AB - Following the introduction in 1988 of a regimen of selective decontamination of the digestive tract (SDD) for extensively injured patients in our burns centre, colonization rates with Gram-negative organisms declined significantly, but colonization with Staphylococcus aureus was unaffected. In an effort to reduce staphylococcal colonization, the SDD regimen has been supplemented with intranasal mupirocin since 1991. In this paper, 33 consecutive patients with burns of > 30 per cent TBSA who were treated with the supplemental regimen (SDD + M) in 1991 and 1992, were compared with 34 consecutive patients admitted in the previous 2 years who were treated with SDD only. Staph. aureus colonization of wounds, sputum and gastric aspirates was significantly reduced in the SDD + M group. Gram-negative colonization rates and the incidence of clinical infections remained low in both groups. Our experience suggests that decontamination of endogenous bacterial reservoirs, in combination with isolation measures to prevent exogenous colonization, effectively prevents infectious complications in patients with severe burns. PMID- 8198736 TI - Reconstruction of human skin from glycerol-preserved allodermis and cultured keratinocyte sheets. AB - The aim of this project was to reconstruct human skin from glycerol-preserved dermis and layers of cultured keratinocytes for use in the treatment of deep burns and ulcers. Glycerol-preserved cadaver skin from the Euro Skin Bank was treated with Dispase II or PBS, under various conditions, to find the best method of retaining the physical structure of the dermis while removing the epidermis and remnants of dead dermal cells which might provoke an allogeneic reaction in a graft recipient. Monoclonal antibodies LH39 and LH7.2, with specificity for basement membrane determinants, showed that treatment with Dispase II resulted in separation of the epidermis from the dermis with concomitant loss of all cellular elements from the dermal layer (as judged by H and E staining). However, when sheets of cultured keratinocytes were applied to the treated dermis and cultured for several days, the keratinocytes attached and regenerated a new basement membrane. PMID- 8198737 TI - Cologne Burn Centre experiences with glycerol-preserved allogeneic skin: Part I: Clinical experiences and histological findings (overgraft and sandwich technique). AB - In an effort to improve the take of finely meshed autografts a modification of the sandwich technique, as first published by Alexander et al. (1981), was developed. In contrast to the techniques described by other authors, the wound bed is sealed with fibrin glue spray after excision of the burns. Widely meshed autografts are then covered with non-meshed (only scarcely sliced) glycerolized allograft sheets, being fixed with staples. Patients are placed on fluidized beds and are exposed without dressings from the fifth day onwards. Histologically and clinically, it can be assumed that part of the glycerolized allodermis is incorporated. During the weeks after transplantation, a creeping substitution of the allodermis by autologous tissue takes place. This would suggest a co existence between glycerol-preserved hypo-allergenic allografts and auto epidermis. Research on the definitive fate of allodermis in cases of sandwich grafting is continuing. PMID- 8198738 TI - Use of glycerol-preserved skin in plastic surgery. AB - It is not always possible to effect immediate closure of wounds and patients' wounds are therefore exposed to risks of desiccation and infection. In the Plastic Surgery Department, Zuider Ziekenhuis, Rotterdam, we have used glycerolized allogeneic donor as a biological dressing in four patients; a polytrauma patient with a compound fracture of the left lower leg; a diabetic with necrotizing fasciitis; a patient with a cat bite on the lower leg, infected with Pasteurella multocida, and a child with large congenital naevi. On clinical grounds there are suggestions of a correlation between the degree of contamination and vascularization of the wound bed and graft take. Furthermore, our experience with the sandwich technique after excision of a large congenital naevus was positive. PMID- 8198739 TI - Use of glycerolized cadaver skin for the treatment of scalds in children. PMID- 8198740 TI - Cologne Burn Centre experience with glycerol-preserved allogeneic skin: Part II: Combination with autologous cultured keratinocytes. AB - Autologous keratinocytes cultured in vitro from skin biopsies of patients with deep partial and full skin thickness burns were grafted onto nine necrectomized wound surfaces between 17 and 25 days after injury. The cells were applied as nonconfluent single cells suspended in fibrin glue. In four wounds, this cell fibrin suspension was used to attach an additional glycerolized allogeneic split thickness skin graft (STSG). Re-epithelialization was very rapid as demonstrated clinically and histologically. Keratinocyte grafted areas without cadaver skin overgraft showed less mechanical stability than when the keratinocyte-fibrin glue suspension was combined with allogeneic STSG. There is clinical and histological evidence that the allodermis may be partially integrated into the new skin. PMID- 8198741 TI - Expansion techniques for skin grafts: comparison between mesh and Meek island (sandwich-) grafts. AB - In skin grafting operations for patients with extensive burn injuries, mesh techniques are often employed to enlarge the effective surface area covered by autografts. However, substantial strips of autograft are required and the distribution of autograft elements on the wound surface is relatively uneconomical. An alternative technique for expanding autografts, first described by Meek in 1958, makes use of a special dermatome and prefolded gauzes to obtain a regular expansion of autograft squares from small pieces of split skin grafts. In a simple in vitro experiment using allograft skin, the expansion ratio obtained with the Meek micrograft technique was measured at almost 1:9. In contrast, the expansion ratio obtained with allograft meshed '1:6' with a Zimmer Dermatome II was measured at 1:4. The maximum distance between the graft elements obtained with the Meek technique was 9 mm, compared to a maximal distance between the strands of the mesh graft of 12 mm. The Meek technique is a useful alternative to mesh grafts when donor sites are limited. Clinical experience suggests that Meek grafts are also particularly suitable for grafting on granulating wounds under poor conditions. PMID- 8198742 TI - Euro Skin Bank: large scale skin-banking in Europe based on glycerol-preservation of donor skin. AB - Although skin banking has been well developed through the years as a means of providing sufficient skin which is instantly accessible to the burn patient, the methods of preservation and the scale on which various institutions bank skin vary considerably. In 1984, the Dutch National Skin Bank started using glycerol as a preservant for skin allografts. Since then there has been a marked increase in both the volume of glycerol skin grafts applied and the area over which these have been distributed. The procedure and organizational aspects of the Euro Skin Bank, as our own institution is now called, and its current method of skin preservation are described. PMID- 8198743 TI - History of the Euro Skin Bank: the innovation of preservation technologies. AB - A skin bank facility is indispensable for burn care. In Holland, a skin bank was established in October 1976 on a national basis for economical reasons. Since 1981, overcoming early rejection by innovation of existing, and development of new, preservation technologies became the main scientific objective. The immunological benefits of glycerolization of skin became clear in 1983. In clinical practice, the use of glycerolized allograft in sandwich grafting changed this technique into a reliable procedure. Early rejection can still be a problem, especially in the non-immunocompromised patient. Future research projects are focused on immunomodulation of the skin by chemical, physical and immunological methods. Even the risk of HIV transmission is not now a drawback for the use of glycerolized skin. PMID- 8198744 TI - Histopathological evaluation of scalds and contact burns in the pig model. AB - A method was developed to inflict standardized scald burns in the New Yorkshire pig. The tissue damage was compared to a standardized contact burn model. On each flank, six localizations were marked in a symmetrical way. Eight scald burns covering 45 cm2 were inflicted by exposing the prepared skin to 500 ml tap water in an applicator at 80 degrees C for 10, 20, 30 and 40 s. Four contact burns were inflicted by applying a brass block of 45 cm2 area, weight 450 gram, with a temperature of 170 degrees C for 10 and 20 s on the skin without exerting pressure. The right flank was used for macroscopic observation, the left flank for histopathological evaluation. Full thickness biopsies were taken at postburn days (PBD) 0, 1, 2, 3 and 21. In the contact burns, a clear demarcation zone of viable and necrotic dermal tissue and vascular damage was observed. The tissue damage in the scalds showed an intermingled pattern of intact and damaged collagen. The more severe scald burns showed a structurally intact superficial vascular plexus, in combination with destruction of the deep vascular plexus. Current and new methods of scald treatment can be classified in this standardized animal model. PMID- 8198745 TI - Cultured epidermal autografts and allodermis combination for permanent burn wound coverage. AB - Cultured epidermal autografts (CEA) have been shown to be an effective permanent skin replacement for major burn injuries, but are more sensitive to adverse conditions than split thickness grafts (Clarke et al., 1988). Cuono et al. (1986, 1987) have described the successful use of engrafted allodermis as a wound bed for cultured grafts. We report on a method of preparing allodermis and grafting CEA in five patients with major burns (48-70 per cent TBSA, average 59.6 per cent). The average age was 38.8 years (20-60 years). All full thickness wounds were excised down to fat within 7 days of admission, and covered with meshed split thickness cryopreserved homograft. Over the ensuing 2-3 weeks, the homograft became engrafted. At surgery, the allo-epidermis was removed, leaving the dermal components as a viable bed for the CEA. Keratinocytes derived from a full thickness biopsy were grown to confluence by the method of Rheinwald and Green (1975), and 25 cm2 sheets were stapled to Vaseline gauze backings and applied to freshly excised wounds. Seven to 10 days after surgery, the gauze backings were removed. The average take ranged from 87-100 per cent (average 93.6 per cent). Follow-up for up to 4 years shows supple skin that has been durable, and resistant to trauma and infection. PMID- 8198746 TI - An animal model to study the significance of dermis for grafting cultured keratinocytes on full thickness wounds. AB - Autologous cultured keratinocytes grafted onto full thickness wounds take poorly, and any epidermal cover that is produced is unstable. However, a more stable epidermis has been reported when keratinocytes are grafted onto a dermal surface. We have developed a skin grafting model using a polytetrafluoroethylene (PTFE) skin graft chamber in the domestic pig. The chambers isolate individual wounds and prevent epithelial migration from the wound edge. Dermal grafts were prepared by enzymatic separation of the epidermis from split skin to leave a de epidermalized dermis (DED). Full thickness wounds were initially grafted with autologous DED and, subsequently, 7 days later with cultured autologous keratinocytes. The wounds were biopsied serially over 6 weeks, and processed for histology, immunocytochemistry and electron microscopy. Clinically, the grafts were seen to mature over the 6-week period. In 14/20 wounds, 40-72 per cent of the wound areas (as assessed by image analysis) had acquired epidermal cover at day 14. In 6/20 wounds, the epidermal cover was 0-27 per cent. The skin surface was stable at day 21. At this time electron microscopy and immunohistochemistry demonstrated a continuous, well formed basement membrane. The epidermis was initially acanthotic, but was histologically mature by day 14. Surprisingly, the dermal grafts were broken down by day 14. However, a neodermis formed beneath all areas with epithelial cover 21 days after grafting the keratinocytes. In this model, we have demonstrated the advantage of providing a dermal bed for cultured keratinocytes. PMID- 8198747 TI - Use of glycerolized human allografts as temporary (and permanent) cover in adults and children. AB - Multiple efforts to achieve immediate and complete burn wound closure following early debridement have been attempted to prevent septic complications, and to decrease the morbidity and mortality associated with major burns. The BG University Hospital Bergmannsheil Bochum (BGUBB) Burn Centre admitted 157 patients with deep partial thickness and full thickness skin burns during 1991 and 1992. Twenty-eight of these patients (18 per cent) were treated with glycerolized human allografts. A total of 57 allograft transplantations were performed on these 28 patients. Our indications for the use of glycerolized human allografts, as well as our results, are presented and discussed. PMID- 8198748 TI - What role does the extracellular matrix serve in skin grafting and wound healing? AB - Recent research on the structure and composition of the extracellular matrix (ECM) now strongly indicates that the major role of this matrix is in regulating cell/cell communication rather than in passively supporting cells. A wealth of structural data on the ECM suggests that there are specific arrangements of sequences within these proteins which profoundly influence the behaviour of the cells moving in that area, with respect to attachment, migration, differentiation and proliferation. In the skin, the ECM can be argued to promote 'appropriate' communication between the keratinocyte and the fibroblast. Skin ECM can be considered to consist both of the large insoluble proteins produced primarily by the fibroblasts, and soluble proteins which may be produced by fibroblasts or keratinocytes and become attached to the ECM. Both the large insoluble and the smaller soluble proteins may constitute signals which influence the behaviour of the keratinocytes. The clinical awareness of the need for a dermal component in skin grafting highlights the need for further research into the way in which the ECM influences keratinocyte/fibroblast biology. Such research will prove relevant to understanding the problems of graft take, graft contracture and scarring. PMID- 8198749 TI - The immunogenicity of glycerol-preserved donor skin. AB - Previous clinical observations have suggested that the application of glycerol preserved donor skin as a temporary wound dressing provokes a weaker rejection reaction than fresh, vital donor skin. Like others, we frequently observed that considerable parts of the allodermis not only remained on the wound for an extended period of time, but even became re-epithelialized in some cases. In order to quantify this effect, we applied the mixed lymphocyte culture (MLC) test in a rat model, using the two highly inbred, histoincompatible rat strains DA and Lewis as donor and recipient respectively. Using the methodology of the Euro Skin Bank, Beverwijk, The Netherlands, split thickness skin, excised from the back of the rats, was equilibrated in 98 per cent glycerol. The immunological reaction after grafting vital DA-skin, glycerolized DA-skin onto Lewis rats, and vital as well as glycerolized Lewis-skin onto Lewis rats was compared. The results of these experiments do not support the clinical observations that the glycerolization procedure results in decreased immunogenicity of donor skin. PMID- 8198750 TI - Virucidal effect of glycerol as used in donor skin preservation. AB - Glycerol has been used for a long time as a viral preservation medium in tissue samples at a 50 per cent concentration, however after a limited time span viruses could no longer be detected. This fact combined with the dehydrating action of glycerol, raised the suspicion that glycerol in a higher concentration could be virucidal. To test this hypothesis, experiments were done at various concentrations of glycerol at three different temperatures (4, 20 and 37 degrees C), using the following viruses: herpes simplex virus, a virus with an envelope, comparable to human immunodeficiency virus; and poliovirus as an example of small, hard to inactivate viruses without an envelope. Glycerol will dehydrate the skin, the extracted water being replaced by glycerol, preserving the original structure. The remaining water is optimally distributed throughout the tissue. However, the possibility exists that glycerol influences the enzymatic processes of nucleic acid breakdown. Plasmid DNA pBR322 was added to HeLa-cells in the presence and absence of glycerol. The outcome of the experiments showed that glycerol has a strong virucidal action. Preservation in 85 per cent glycerol was preferred, because using this concentration the glycerolized allograft skin retained its suppleness and was easy to manipulate during operations. PMID- 8198751 TI - Cohort study of HIV infection among drug users in Ruili, Longchuan and Luxi of Yunnan Province, China. AB - In March 1992, KAP investigation and HIV blood test were carried out for 860 drug users and 82 spouses in Ruili, Luxi, Longchuan of Yunnan Province, China. The results showed that there were 285 injecting drug users (IDUs) (33.1%) among 860 drug users. Among 282 blood samples of IDUs, the HIV infection rate was 49.0%, highest in Ruili (81.8%, 63/77), then Longchuan (44.6%, 74/166), lowest in Luxi county (5.1%, 2/39). Twelve new HIV(+) were found from 75 persons, who had been tested as HIV(-) in recent two years. Sixty-two blood samples were collected among 82 spouses of IDUs with HIV(+), and 6 were HIV(+) (9.8%), with an increase of 6.7% compared with results of the investigation two years ago (3.1%, 2/64). PMID- 8198752 TI - Unity and diversity of responses to xenobiotics in organisms. AB - A conceptual treatment of the mechanisms involved in the process of toxicosis by diverse agents in different tissues indicate a likely unspecific, common, central process in addition to specific precipitating factors acting on a particular site in a cascade of events. Free radicals, membrane functions and calcium functions appear to be links in the common pathway. Such a central mechanism could be interrelated with immunological defenses as well as genotoxic changes at different sites, suggesting parallel or related evolution of these antistress mechanisms. Many radical scavengers, antioxidants, membrane stabilizers, nutritional supplements and calcium modulators have proved beneficial either in reducing toxic impact, delaying the development of lesions or even reversing the effects. Similarly, recent evidences show that some immunomodulators can act as antioxidants and antigenotoxicants. Thus, the status of body defenses which may vary from one individual to the other have a role in deciding the effects under the same quantified risks with varying relative responses. Whether modulation of physiological defenses against stress could help in developing prophylactic measures remains an open question. PMID- 8198753 TI - Modification by polychlorinated biphenyls (PCBs) of cadmium induced lesions in the planarian model, Dugesia dorotocephala. AB - The appearance of abnormal growths on the planarian, Dugesia dorotocephala, in response to cadmium with and without pre-exposure to L-buthionine-R, S sulfoximine (BSO) and concurrent exposure to the polychlorinated biphenyls (PCBs) Aroclor 1254, PCB 28, PCB 110 or PCB 126 is described. Pigmented rose thorn (PRT) lesions were non-invasive and appeared in response to PCBs. Post-head (PH) lesions developed in up to 100% of the animals within 6-20 days post-dosing, progressed rather rapidly and were highly invasive. Round tail tip (RTT) lesions appeared in lower frequencies within 10-30 days, but progressed extremely rapidly resulting in tail loss within 48 h. We have referred to these types of lesions as "tumors", but they are not necessarily characteristic of vertebrate neoplasms. PCBs interacted with cadmium in a complex way, in some cases increasing total lesions and decreasing time-to-lesion and in other cases having the opposite effects. A three-factor (PCB, PCB dose, Cd dose) nested analysis of variance model was used to determine lesion rates in order to compare PCB potencies as potentiators or antagonists. The Aroclor mixture was always the least potent co toxicant but appeared to be the most potent antagonist; the coplanar PCB 126 was the most potent co-toxicant. The complex response surfaces and the lack of stoichiometry in dose-response relationships indicate that multiple mechanisms are responsible for PH and RTT lesions in planarians. These results emphasize the complexity of PCB toxicities and suggest further studies to validate the planarian model as a screen for combinations or environmental mixtures which may have altered biological potency in other species. PMID- 8198754 TI - Effect of fertilizer diammonium phosphate on liver, kidney and muscle 5' nucleotidase activity of fresh water teleost fish Clarias batrachus. AB - The toxic effect of fertilizer Diammonium phosphate resulted in alterations of 5' Nucleotidase activity of tissues--liver, kidney and muscles of fish C. batrachus at varying intervals and exposures. Alterations in 5'-Nucleotidase activity of body organs gave an idea of the toxicity caused by the fertilizer. Thus the enzyme 5'-Nucleotidase can be used to monitor the pollution in aquatic ecosystem. PMID- 8198755 TI - High performance liquid chromatographic determination of phenolic acids in fruits and vegetables. AB - A simple isocratic HPLC technique has been developed for the quantitative analysis of phenolic acids (PAs) in fruits and vegetables. Nine benzoic and cinnamic acid derivatives were separated in less than 30 min, and the resolution was all more than 1.23. The ranges of linearity for PAs standards were 0.2-100 ng, even up to 600 ng (r = 0.983-1.000) and the detection limits were 0.02-0.24 mg/kg. Samples of fresh vegetables and fruits were extracted with 80% methanol and ethyl acetate, then purified with C18 Sep-Pak cartridge and determined by HPLC. This method was applied to the determination of PAs in 7 kinds of fruits and vegetables, i.e., apple, pear, Chinese cabbage, cauliflower, turnip, soybean sprout and white grape wine. The content of the 9 PAs varied widely in the 7 kinds of foods studied. The average concentrations of chlorogenic acid in apple (100.2 mg/kg) and pear (30.8 mg/kg) were quite high, and sinapinic acid was remarkable (42.5 mg/kg) in Chinese cabbage, and protocatechuic acid had the highest concentration of all the PAs in white wine. PMID- 8198756 TI - Pneumoconiosis: the changes of peripheral airways. AB - Ultrathin bronchofiberscope (Olympus BF-1.8T) was applied to the observation of the peripheral airways of total 87 cases, including 73 cases of quartz-exposed and asbestos-exposed workers with/without pneumoconiosis (exposure groups), and 14 cases of controls. The changes of peripheral airways in exposure group of non smokers was found, mainly to be pigmentation, elevation, irregularity and lustlessness on the surface of the bronchiole walls, and predominantly stenosis and ectasis of the lumen. The detectable rate was higher in peripheral airways than in central airways. Some changes existed in early stage and some had a tendency of increasing detectable rate with category progressing. Some factors such as smoking could influence the results of analysis. PMID- 8198757 TI - Histopathological changes in the epidermis of the air breathing catfish Heteropneustes fossilis exposed to sublethal concentration of mercuric chloride. AB - Histopathological alterations induced by the sublethal concentration of (0.03 ppm) mercuric chloride solution on the epidermis of the fresh-water catfish Heteropneustes fossilis have been studied. It induces slow but significant histopathological changes in the various cellular components of the epidermis. It induces vacuolization, necrosis and pycnosis of the nuclei of the epithelial cells which subsequently shed. Loosening of epithelial cells of the outermost and middle layers following degeneration of the intercellular material and widened intercellular spaces is another important alteration. Prolonged mercury treatment also causes a gradual decrease in staining intensity for sulphated glycosaminoglycans in the outer border of the most superficial layer epithelial cells. The glandular elements (club cells and mucocytes) also get affected, showing cyclic degeneration followed by regeneration. PMID- 8198758 TI - The problems of the safety evaluation of biotechnology derived drugs. PMID- 8198759 TI - Clinical study on death in Behcet's disease. AB - We were able to identify 7 patients who died of Behcet's disease, among 2,200 patients registered at the Behcet's Disease Specialty Clinic of Severance Hospital from November 1983 to October 1992. Six were male and one female. Age of death was 31 to 55 years with the mean age of 39.1. The age of onset was 24 to 54 years with the mean age of 32.6. The mean duration of illness was 6.5 years. The most frequent initial symptom was oral ulcer, with the most common type being the incomplete type in Shimizu's classification. Positive pathergy tests were found in all the 5 patients in whom the test was performed out of 7 patients. Various modalities of treatments such as oral steroid, colchicine, azathioprine, colectomy, and pacemaker insertion were attempted without outstanding therapeutic effects. The causes of death were gastrointestinal bleeding, bowel perforation, superior and inferior vena cava syndrome, aortic regurgitation, cerebrovascular disease, sepsis, and lung abscess. PMID- 8198760 TI - A complete remission can be achieved despite persistence of abnormal bone marrow promyelocytes in acute promyelocytic leukemia--experience in 2 patients. AB - Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia (AML) and is distinguished from other subsets of AML by its distinctive morphology, specific chromosomal abnormality, associated consumptive coagulopathy, and response to treatment. Interestingly, patients with APL frequently enter complete remission without undergoing a characteristic period of bone marrow hypoplasia. In two cases in this report, complete remission was achieved without bone marrow hypoplasia without further additional course of chemotherapy despite the appearance of persistent malignant cells in the bone marrow after first induction chemotherapy. During the period of treatment, severe coagulopathy occurred in both cases but resolved as the patients entered into remission. Remission in patients with APL may occur even when induction therapy fails to cause marrow hypoplasia or to eradicate replicative cells. To avoid unnecessary exposure to toxic therapy, caution should be exercised in assessing the adequacy of remission induction treatment. PMID- 8198761 TI - Pharmacokinetic comparison of two valproic acid formulations--a plain and a controlled release enteric-coated tablets. AB - We investigated the single- and multiple dose pharmacokinetics of a new controlled-release formulation (Orfil retard enteric coated tablet) of valproic acid in comparison with those of the plain tablet as a reference. Twelve healthy volunteers were given each formulation of 300 mg in the single-dose study. In the steady-state multiple-dose study, twelve epileptic patients received 1200 mg/day of the reference drug (300 mg 9 AM, 300 mg 3 PM, 600 mg 9 PM) and the test formulation (600 mg 9 AM, 600 mg 9 PM) with at least one week interval in cross over manner. The AUC values of the test controlled release formulation were 91.7% (95% confidence interval: 78.4-100.4%) of the reference drug in the single-dose study and 98.2% (95% confidence interval: 86.2%-109.9%) in the steady-state study. The AUC's of the two formulations were not significantly different by ANOVA test. The Cmax and Tmax values of the test formulation were significantly different from the values of the reference in single-(Tmax: 158.4%, Cmax: 52.5% of the reference) and multiple-dose study (Tmax: 153.5% of the reference). The MRT values of the test formulation were also significantly greater (129.4% of the reference) in the single-dose study. Regarding the controlled-release characteristics of the test formulation, fluctuation index and percentage fluctuation of the twice a day dosage regimen of the test formulation were comparable with those of the thrice a day dosage regimen of the conventional tablet. Area deviation was even smaller in the test regimen of the controlled release formulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198762 TI - Detection of chromosome aberrations in interphase nuclei using fluorescence in situ hybridization technique. AB - We report here several experiences of interphase cytogenetics, using fluorescence in situ hybridization (FISH) technique, for the detection of chromosome aberrations. FISH, using alpha satellite specific probes of 18, X, Y chromosomes, was done in interphase nuclei from peripheral blood of patients with Edwards' syndrome, Klinefelter's syndrome and Turner's syndrome with healthy male and female controls, respectively. The distributions of fluorescent signals in 100 interphase nuclei were well correlated with metaphase findings. Nowadays FISH plays an increasingly important role in a variety of research areas, including cytogenetics, prenatal diagnosis, tumor biology, gene amplification and gene mapping. PMID- 8198764 TI - Trends in radiation therapy facilities-1986 to 1991. AB - The Korean Society of Therapeutic Radiology has periodically conducted a national survey on the status of radiation therapy facilities in Korea. This paper summarized survey data on the status of radiation therapy facilities, manpower, megavoltage equipments, patient load, types of procedures performed and characteristics of the patients treated. PMID- 8198763 TI - Apolipoprotein E genotypes of normal and hyperlipidemic subjects. AB - Apolipoprotein E (apo E) plays a role in the regulation of the lipid metabolism of humans. Apo E, 229 amino acid polypeptide, is classified into three major isoform (E2, E3, E4) according to the differences of amino acid in position 112 and 158. In the normal population apo E3 isoform is most prevalent and apo E2 or E4 is frequently associated with hyperlipoproteinemia. To find out the frequency of apo E isoform distribution in the Korean population, apo E genotyping was performed. After amplification of apoE gene by polymerase chain reaction (PCR), restriction isotyping was done by cleavage with restriction enzyme Hha I and polyacrylamide gel electrophoresis. The apo E allele frequency in 73 normal subjects was 4.8% for E2, 84.9% for E3 and 10.3% for E4. In diabetic patient with hyperlipoproteinemia, the frequency of apo E allele was 6.3% for E2, 81.0% for E3 and 12.7% for E4. There was no significant difference in apo E isoform distribution between diabetics and normal populations. But in patients with cardiovascular disease with hyperlipidemia, the apo E4 allele frequency was significantly higher than normal (20.0% vs 10.3%, p < 0.005). Apo E3 was the most common isoform in normal and diabetic subjects and apo E2 isoform was rather low frequency compared to Caucasians. This pattern is similar to the Japanese population but somewhat different from other populations. From the data of a high association of apo E4 allele and cardiovascular disease with hypercholesterolemia, apo E isoform may be one of the determinants of hyperlipoproteinemia. The PCR method may be useful in apo E genotyping. PMID- 8198765 TI - Epidemiology of cerebrovascular disease in Korea--a Collaborative Study, 1989 1990. Korean Neurological Association. AB - We present epidemiologic, etiologic, and clinical data for 3,021 patients with cerebrovascular disease admitted to the 17 regional hospital centers from all over Korea from 1989 to 1990. Each case was coded retrospectively into a computerized registry using a standard protocol. This study was conducted to provide baseline data on recent patterns on cerebrovascular disease in Korea and to evaluate any temporal trends compared with previous reports. It is the largest hospital-based study and gives a rough estimate of the current stroke profiles in Korea. Although there might be some selection bias in several hospitals, the distribution of cases by type of stroke was: thrombosis (27.2%), lacular infarction (11.2%), transient ischemic attack (3.0%), embolism (7.0%), intracerebral hemorrhage (31.4%), subarachnoid hemorrhage (18.0%), intraventricular hemorrhage (1.5%), and others (0.7%). The overall incidence rate of cerebral thrombotic strokes (41.1%) was higher than that of intracerebral hemorrhage (31.4%) which was the reverse in most of previous reports before 1980s. This study suggests a changing trend of stroke patterns in Korea and a multicenter prospective study using more complete registry protocols is required for an accurate evaluation. PMID- 8198766 TI - Case of difficult intubation overcome by the laryngeal mask airway. AB - A case of difficult intubation is described in which the problem was overcome by use of the laryngeal mask airway (LMA). The patient had difficulty in mouth opening due to severe burn scar contracture around the mouth and limited access prevented tracheal intubation. The use of LMA is shown to have obviated the need for tracheal intubation in the case of a patient whose injuries would have made this technique difficult. PMID- 8198767 TI - Preenhanced computed tomographic findings in brain death. AB - A patient complying with the clinical criteria for brain death was studied by preenhanced computed tomography (CT). Preenhanced CT showed apparent increased density at the base of the brain along the course of the major arterial vessels, and abnormally dense-appearing deep venous structures, like those of contrast enhanced CT. There was a diffuse decrease in brain density with a poorly delineated ventricular system. These CT findings were very characteristic. CT as a non-invasive method seems to be valuable in the diagnosis of brain death. The relevant literature is reviewed and mechanisms showing those CT findings are discussed. PMID- 8198768 TI - Meningioangiomatosis--a case report. AB - Meningioangiomatosis is a rare benign hamartomatous lesion. We describe a case of meningioangiomatosis in an 18-year-old boy with a 15 year history of seizures. Computed tomography reveals an irregular calcification density along the right temporal gyrus. Microscopically, irregularly branched blood vessels, surrounded by a concentric arrangement of proliferating spindle cells, are extending into the gray matter from the meningeal surface. Ultrastructural and immunohistochemical examination failed to demonstrate features of meningothelial cell origin in this case. This is the first case of meningioangiomatosis published in Korea along with immunohistochemical and electron microscopic studies. The pathogenesis and previous reports of this lesion will be discussed. PMID- 8198769 TI - Multicore myopathy--a case report. AB - Multicore myopathy is a rare congenital myopathy. The multicores consist of numerous small areas of decreased oxidative enzyme activity. The long axis of the lesion is perpendicular or parallel to the long axis of the muscle fiber. These cores are usually smaller than central cores. For this reason they are also called minicores. Although the multicores represent a nonspecific change in that they can be observed in malignant hyperthermia, muscular dystrophy, inflammatory myopathy, etc. Muscular weakness dating from early infancy is combined large proportion of the muscle fibers. In about half of the reported cases the muscular weakness has not been progressive, while in the others a slow progression has occurred. This 9-year-old boy presented with congenital nonprogressive myopathy associated with thoracic scoliosis and bilateral equinovarus deformity. The serum creatine phosphokinase and lactic dehydrogenase levels were normal. Electromyography showed "myopathic" features. The biopsy revealed a marked size variation in myofibers, ranging from 10 microns to 100 microns. A few small angular fibers and slight endomyseal fibrosis were also noted. There was type I fiber predominance. NADH-TR reaction disclosed more well-defined cores with loss of intermyofibrillary mitochondrial activity. These cores were usually located with loss of intermyofibrillary mitochondrial activity. These cores were usually located in the peripheral portions of the myofibers and the core size measured 10 30 microns in diameter. Electron microscopic examination revealed circumscribed areas of disintegrated Z band material and disorganized sarcomeric units near the sarcolemma. A decrease in the number of mitochondria and glycogen particles was noted. PMID- 8198770 TI - Factors used by physical medicine and rehabilitation residency training directors to select their residents. AB - A 17-item questionnaire was designed to assess the relative importance of various factors to physical medicine and rehabilitation (PM&R) training directors when ranking PM&R resident applicants during the National Resident Match. The questionnaire was sent to all PM&R residency training directors. The recipients were asked to grade most selection factors based on a numerical scale: 1, unimportant; 2, some importance; 3, important; 4, very important; 5, critical. The specific factors addressed in the questionnaire were: academic criteria, letters of recommendation, individual applicant characteristics and aspects of the interview process. Twelve yes-or-no questions were also designed to determine the weight that residency training directors place on certain academic criteria. A response rate of 88% (66/75) was obtained. The most important academic criteria were grades in a PM&R clerkship in their facility (4.1 +/- 0.8), followed by grades in a PM&R clerkship in another facility (3.6 +/- 0.9). The most important letters of recommendation were from a PM&R faculty member in the respondent's department (4.0 +/- 0.8), followed by the dean's letter (3.7 +/- 1.0) and the PM&R chairman's letter (3.7 +/- 1.0). The three most important applicant characteristics evaluated during the interview were compatibility with the program (4.4 +/- 0.8), the ability to articulate thoughts (4.2 +/- 0.8) and the ability to work with the team (4.2 +/- 0.8). Most program directors used multiple criteria to complete their rank list, but the most important were based upon the interview (4.5 +/- 0.9), letters of recommendation (3.7 +/- 0.9), medical school transcript (3.6 +/- 0.8) and the dean's letter (3.6 +/- 1.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198771 TI - A gender specific wrist ratio and the likelihood of a median nerve abnormality at the carpal tunnel. AB - The objective of this study was to clarify the significance of the association of the patient wrist ratio and a median abnormality at the carpal tunnel. The average wrist ratio and median nerve latencies were determined in 665 patients with symptoms involving at least one hand or forearm. The mean average wrist ratio of the 419 women (0.690) exceeded that of the 246 men (0.672), differing significantly (mean difference 0.018; 95% confidence interval, 0.012 to 0.024; P < 0.0001). The mean average wrist ratio of the 236 women (0.704) with a median abnormality exceeded that of the 183 women (0.672) without a median latency abnormality (difference 0.032; 95% confidence interval, 0.026 to 0.038; P < 0.0001); the mean average wrist ratio of the 166 men (0.681) with a median abnormality exceeded that of the 80 men (0.655) without a median latency abnormality (difference 0.026; 95% confidence interval, 0.016 to 0.035; P < 0.0001). Regression analyses revealed an increasing average wrist ratio to correlate positively with a slowing of the dominant hand median nerve motor and sensory latencies, with the best latency correlation being the median minus the ulnar palm-to-wrist latency difference in the women (r = 0.394, P < 0.0001) and in the men (r = 0.329, P < 0.0001). A median abnormality was found in 79% of the women and in 86.9% of the men with an average wrist ratio of 0.7 or greater; women had 73.8% of the average wrist ratios of 0.7 or greater.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198772 TI - Nonfatal wheelchair-related accidents reported to the National Electronic Injury Surveillance System. AB - To better understand the epidemiology of accidents affecting wheelchair users, we evaluated 2,066 nonfatal wheelchair-related accidents reported, between 1986 and 1990, to the National Electronic Injury Surveillance System (NEISS) Division of the United States Consumer Product Safety Commission. The NEISS used data from representative emergency departments across the United States during this period. An extrapolation from this sample and from those of 1991 and 1992 provided an average national estimate of 36,559 wheelchair-related accidents per year that are serious enough to cause the injured person to seek attention at an emergency department; there was a significant (P = 0.007) upward trend over time. Elderly women were the most likely to sustain an injury. Of the people injured, 7.6% were not wheelchair users themselves. The most common causes of accidents were related to falls and tips in 73.2% of incidents, associated secondary causes (e.g., a ramp) in 41.4% and transfers in 16.9%. The most frequently reported location for the falls was at home (50.8%). The majority of resulting injuries were contusions and abrasions (32.8%), lacerations (28.0%), fractures (20.2%) and sprains and strains (10.3%). Hospitalization was required in 12% of cases. The results of this analysis have implications for rehabilitation professionals, regulatory bodies and wheelchair manufacturers. PMID- 8198773 TI - Standardized nerve conduction studies in the lower limb of the healthy elderly. AB - Nerve conduction studies are commonly performed in elderly individuals. No complete set of reference data for the distal lower limb nerves exists for this population, making it difficult to accurately interpret electrodiagnostic findings. The purpose of this study was to provide reliable reference data by comprehensively examining conduction characteristics in routinely tested peripheral nerves of the lower limb in a healthy elderly population. Conduction studies of the tibial, deep peroneal, sural and medial dorsal cutaneous nerves were performed in one lower limb of 122 healthy elderly individuals between the ages of 60 and 89 years. Peak amplitudes of the sural sensory action potential and the tibial compound muscle action potential correlated significantly with both age and leg length. All other parameters did not show significant correlation with age. Conduction velocities and distal latencies slowed significantly with increasing leg length except for tibial distal latency. PMID- 8198774 TI - Predicting depression and psychological distress in persons with spinal cord injury based on indicators of handicap. AB - This study examined whether experiences of handicap influence levels of depression and distress among persons with spinal cord injury (SCI) during the years after initial discharge from rehabilitation. SCI outpatients (163), who had received inpatient treatment at one of two rehabilitation centers in Michigan and who were between 2 to 7 years since injury, participated in the study. Measures of depression, of psychological distress and of handicap were collected during 2 consecutive years utilizing the Zung Self-Rating Scale, the Brief Symptom Inventory and the Craig Handicap Assessment and Reporting Technique (CHART) in conjunction with the Perceived Handicap Questionnaire (PHQ), respectively. According to the study's findings, depressed/distressed SCI subjects reported spending more hours in bed (P < 0.01), fewer days out of the house (P < 0.03) and receiving more paid personal care assistance (P < 0.02) than did other subjects. They also expended more for general medical expenses (P < 0.001) and reported less access to readily available transportation (P < 0.003). CHART total scores, reflecting a simple objective measure of handicap as described by Whiteneck et al. (Whiteneck GG, Charlifue SW, Gerhart KA, Overholser JD, Richardson GN: Guide for Use of the CHART: Craig Handicap Assessment and Reporting Technique. Craig Hospital, CO, 1988) were significantly associated with both distress and depression as measured during the second year of data collection. Other significant predictors of depression and distress included subjects' self perceived handicap (measured by the PHQ), gender, marital status and age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198775 TI - Magnetic resonance imaging of osteonecrosis and osteoarthrosis in exercising quadriplegics and paraplegics. AB - Degenerative bone and joint diseases that commonly accompany spinal cord injury (SCI) may be exacerbated by physical activity of the lower extremities. To determine if orthopaedic stress imposed by electrically stimulated cycling exercise is associated with osteonecrosis or osteoarthrosis in persons with chronic SCI, ten quadriplegics and paraplegics who had each undergone electrical stimulation cycle ergometry exercise two or three times weekly for longer than 1.5 years underwent magnetic resonance examinations of the femoral heads and the dominant knee. Three of the ten subjects had no evidence of meniscal or bone marrow pathologies, osteochondritis dessicans, avascular necrosis, joint effusion or accumulation or soft tissue tears. The magnetic resonance scans of six subjects were noted to have very mild effusion, slight meniscal degeneration and minimal chondromalacia patellae. Consistent patterns of bone or joint pathology were not discernible among these scans, and the positive findings did not represent threatening clinical states. The scans of one subject showed heterogenous regions of bone infarct characteristic of osteochondritis and avascular necrosis, observations that were atypical of all other subjects. No injuries consistent with the biomechanics of cycling exercise were observed in any subject. Despite the high sensitivity of magnetic resonance imaging in detecting bone and joint deterioration, significant bone and joint findings represented only 14 of 150 observations, less than previously reported in sedentary subjects with SCI. This study suggests that electrical stimulation cycle ergometry does not foster bone or joint deterioration in individuals with chronic SCI. PMID- 8198776 TI - Electrophysiologic studies in tarsal tunnel syndrome. Diagnostic reliability of motor distal latency, mixed nerve and sensory nerve conduction studies. AB - The tarsal tunnel syndrome (TTS) is an entrapment of the posterior tibial nerve at the ankle, which, like carpal tunnel syndrome, improves with surgery but needs an instrumental diagnosis to exclude other diseases. This study was performed to evaluate the diagnostic value of nerve conduction tests proposed for the diagnosis of TTS. Of the 13 patients who were investigated 12 had secondary unilateral and 1 idiopathic bilateral TTS. One or more neurophysiologic parameters were abnormal in all cases. The diagnostic value of each neurophysiologic parameter was calculated by comparing conduction on the affected side with conduction on the healthy side of each patient with TTS. The accuracies of the sensory nerve action potential and mixed nerve action potential, both after stimulation of the plantar nerves, were almost the same, with sensory nerve action potentials more sensitive and less specific and mixed nerve action potentials less sensitive and more specific. Because from the clinical point of view we must be more afraid of false-positive results, the mixed nerve action potential is recommended for presurgical diagnosis of TTS. Coexistence of mixed nerve and sensory nerve action potential abnormalities, especially if asymmetric, are highly indicative of TTS. PMID- 8198777 TI - Survival of individuals with spinal muscular atrophy on ventilatory support. AB - Six ventilator-assisted individuals (VAIs) with spinal muscular atrophy (SMA) are described. All six survived by using intermittent positive pressure ventilation via an indwelling tracheostomy for a mean of 11.7 +/- 17.7 yr despite frequent episodes of mucus plugging and pneumonia. Four of the VAIs also received all nutrition via indwelling gastrostomy tubes because of severe bulbar muscle weakness. Four VAIs used tracheostomy intermittent positive pressure ventilation with their tracheostomy cuffs deflated and could communicate verbally. Five of the six VAIs remained institutionalized from the onset of ventilatory use. Two SMA VAIs survived for 15 and 4 yr, respectively, despite need for ventilatory support since early infancy. All four SMA VAIs who could communicate remained socially active and one, gainfully employed. We conclude that for patients with advanced SMA markedly prolonged survival is possible with ventilatory assistance despite severe respiratory and bulbar muscle dysfunction. PMID- 8198778 TI - A computer-aided walking rehabilitation robot. AB - Even with recent techniques, a significant number of patients with multiple injuries cannot be mobilized at an early stage despite the fixation of all fractures. Conventional mobilization aids are not able to provide the prescribed weight bearing needed in fractures, especially those involving both the lower limbs. Robotics is a current technology aimed at improving the quality of medical care. To this end, Takatoshi Ide developed the mobility rehabilitation robot, the REHABOT. This apparatus facilitates rehabilitation by providing secure postural support and prescribed weight bearing during ambulation. The REHABOT has been used for early mobilization and gait training of severely disabled patients at different hospitals in Japan during the last 6 years. In most of the cases, this training has resulted in earlier improvement of ambulatory capability. In this paper we report the use of this device for early ambulation in two patients with multiple fractures involving the extremities and the spine. Early mobilization was achieved by initially reducing the weight bearing to 30% of body weight followed by a gradual increase governed by patient tolerance. The average length of training for these two patients was 18 days. The average total distance was 5.5 km and total walking duration was 4.5 h. After the completion of the training both patients were able to walk independently. PMID- 8198779 TI - Interdepartmental education and collaboration in the academic setting. A commentary. PMID- 8198780 TI - A clinician's guide to decision making capacity and ethically sound medical decisions. AB - Competence, or decision making capacity, refers to a patient's ability to understand a situation and to make a choice in light of that understanding. It requires the physician to disclose adequate information so that the patient is able to understand and choose. The standard for determining competence is that a person is deemed competent to make medical decisions if the person is capable of giving informed consent. The crucial ethical issue is whether the patient understands and appreciates the nature of the treatment, the risks and benefits, the alternatives and the consequences. Although there is no universally accepted test of a patient's capacity to consent to treatment, the "knowledge and understanding" test offers clinicians a simple competence test that can be administered at the bedside. The physician first identifies the information needed for the patient to give informed consent. Then the physician determines the patient's understanding and appreciation of that information by means of five objective questions. Ultimately, talking to the patient is the only way to determine if the patient is capable of making a medical decision. Of particular ethical interest, however, is rehabilitation medicine's efforts to exempt itself, in the early stages of rehabilitation, from the "moral force" of informed consent. Relying on its unique characteristics as a medical specialty, and on the fact that some of its patients have suffered sudden onset of severe impairment, rehabilitation medicine appears poised to espouse the "thank you theory" of medical practice. In addition, physiatrists may have a professional obligation to fully inform patients when potentially beneficial treatment is withheld from them, such as when they are denied access to or terminated from rehabilitation. PMID- 8198781 TI - Is there a role for educators in health care? PMID- 8198782 TI - A systematic approach to functional reconstruction of the oral cavity following partial and total glossectomy. AB - Mobility, sensation, volume, and to a lesser extent, the shape of the tongue following partial glossectomy are critical elements to the successful rehabilitation of the patient with oral cancer. Our approach to tongue reconstruction is based on the extent and functional status of the residual tongue and whether there is an associated mandibulectomy. Despite the devastating effects of ablative surgery and radiation, the application of available reconstructive techniques can help to improve the quality of life of these patients. Herein, we present a revised classification scheme for tongue defects along with a discussion of the optimal method for reconstruction based on available techniques. PMID- 8198783 TI - Intraoral monocortical miniplating of mandible fractures. AB - OBJECTIVE: Intraoral monocortical miniplate fixation of mandibular fractures provides simultaneous visualization of the fracture and occlusal relation, while almost eliminating external incisions and potential compromise of the marginal mandibular nerve. We sought to analyze the outcome of our patients treated with this technique and compare this with literature standards for mandible fracture repair outcome. DESIGN: A retrospective analysis of outcomes for a case series. SETTING: All treatment performed in inner city, level 1 or 2 trauma rated, teaching hospitals. PATIENTS: During a 5-year period, 287 patients with 499 mandible fractures were treated with intraoral miniplates. Follow-up criteria was available for a retrospective analysis of 246 patients with 432 fractures of the mandible. INTERVENTION: Intraoral monocortical plating techniques were used to treat 313 of these 432 mandibular fractures. MAIN OUTCOME MEASURES: All complications of bone union, occlusion, wound infection, and dehiscence were graded and tabulated. RESULTS: On analysis of the miniplated fractures, 1.2% of the patients had delayed union, 0.4% had non-union, 6.5% had postoperative wound infection develop, and 4.1% had varying degrees of malunion. Complication rates are comparable with most reported studies of bicortical and monocortical plating of mandible fractures. CONCLUSIONS: Monocortical miniplate fixation is a reliable method of providing rigid fixation. It offers a reasonable alternative to bicortical plating in most mandible fractures. PMID- 8198784 TI - Precise repair of orbital maxillary zygomatic fractures. AB - OBJECTIVE: To demonstrate the techniques, advantages, indications, and potential pitfalls of the transconjunctival approach with lateral canthotomy, sublabial approach, and coronal approach in the treatment of complex trimalar fracture with associated blow-out fractures. DESIGN: All patients diagnosed as having complex trimalar fractures with or without blow-out treated by either of us over a 2-year period were included. Follow-up ranged from a minimum of 6 months to 2 years. SETTING: All patients were treated with December 1989 to December 1991 at either Louisiana State University Medical Center, Shreveport, or University of Kansas Medical Center, Kansas City. PATIENTS: Eighteen patients with complex trimalar fractures were included in this study. Eight patients had associated orbital blow out fractures. Simple isolated arch fractures were excluded. INTERVENTION: All subjects underwent a transconjunctival approach with lateral canthotomy. Seven subjects also had associated sublabial flaps. Five patients required hemicoronal or coronal approaches. RESULTS: There were seven minor complications. Ninety three percent (14/15 [three didn't respond to the survey]) of patients surveyed were either very satisfied or satisfied with their functional and cosmetic results. CONCLUSION: The management of complex trimalar fracture with blow-outs is greatly facilitated by the rational application of the described techniques. PMID- 8198785 TI - Transsinus reduction and one-point fixation of malar fractures. AB - OBJECTIVE: To describe and evaluate transsinus reduction and one-point miniplate fixation of the zygomaticomaxillary buttress for the treatment of tripod malar fractures. DESIGN: A consecutive case series. SETTING: Private otolaryngology practice. PATIENTS: A consecutive sample of 17 patients presenting with isolated tripod malar fractures over a 42-month period. INTERVENTION: A gingivobuccal sulcus incision is made. Access into the maxillary sinus was obtained through an invariably comminuted inferior fracture line. The zygoma was reduced by applying lateral and anterior traction force to the zygomatic recess of the maxillary sinus. Miniplate fixation of the zygomaticomaxillary buttress area was then performed bridging over an area of bone loss and comminution. MAIN OUTCOME MEASURES: Clinical assessment of facial symmetry by patients, physician, and roentgenographic studies. RESULTS: All patients presenting with no comminution of the orbital rim had complete restoration of their premorbid facial symmetry. One of the two patients presenting with comminuted orbital rim had poor results. CONCLUSIONS: This technique is simple, limited, and successful in treating most malar fractures. The lack of comminution of the orbital rim is crucial for the stability of the reduced zygoma. A simple and clinically relevant classification of malar fractures is proposed. PMID- 8198786 TI - Microvascular free flaps in head and neck reconstruction. Report of 200 cases and review of complications. AB - OBJECTIVE: Microvascular free-tissue transfer to the head and neck has become an accepted method of reconstruction owing to increased success rates and superior aesthetic and functional results. Although the large number of arteries and veins in the neck make free-flap revascularization easier than in other recipient sites of the body, there are also unique problems that pose significant risks to the success of the procedure. We report our experience with 200 microvascular free flaps performed between 1987 and 1992. SETTING: This study was conducted at a tertiary referral center. PATIENTS: The majority of patients in this series underwent surgery for squamous cell cancer. Approximately 75% of the reconstructions were performed for defects of the oral cavity. There were 120 vascularized bone-containing free flaps for mandibular and midface reconstruction. The remaining 80 soft-tissue flaps were used for a variety of defects ranging from the scalp to the pharyngoesophagus. RESULTS: An overall success rate of 93.5% for free-tissue transfers is reported. Greater experience with this technique has resulted in a reduction and a change in the nature of the complications encountered compared with those seen in the early part of our series. Donor and recipient site complications, including flap failures and anastomotic revisions, are analyzed in detail with respect to age, radiation status, donor site, and whether the ablative procedure was done for a primary or recurrent neoplasm. PMID- 8198787 TI - Voice quality after laryngotracheal reconstruction. AB - OBJECTIVE: To ascertain changes in laryngeal anatomy and function associated with poor voice outcome after laryngotracheal reconstruction (LTR) and to specifically describe dysphonia in pediatric patients treated for subglottic stenosis. DESIGN: A survey was undertaken of patients having undergone LTR for subglottic stenosis. Twelve patients were recruited during the year 1990-1991. Nine patients were able to complete the endoscopic portion of the protocol that included fiberoptic and direct laryngoscopy. Speech samples were qualitatively evaluable in only six of nine patients (vocal quality, loudness, and intelligibility) and objectively in five of nine patients (fundamental frequency and pitch perturbation). PATIENTS: All patients in this consecutive sample had undergone LTR for congenital or acquired subglottic stenosis. The average age was 6 years. Each patient had previously undergone an average of two prior open laryngeal procedures and five endoscopic procedures. OUTCOME MEASURES: Correlation between anatomic and functional changes in the post-LTR larynx and voice outcome. RESULTS: Endoscopic evaluation of the post-LTR larynx showed a 78% incidence of altered anatomy and 44% incidence of altered function. Speech sample analysis showed the following: 100% decreased vocal quality, 50% decreased intelligibility, 100% decreased volume, and 80% low fundamental frequency and increased jitter. CONCLUSIONS: Children with high-grade subglottic stenosis and multiple prior surgeries are at high risk for poor voice outcome after LTR. Future prospective studies will allow substantiation of this observation and clarification of which changes in laryngeal structure and function arise from surgery per se. PMID- 8198788 TI - Mechanism of tracheoesophageal shunt phonation. AB - OBJECTIVE: To elucidate the phonatory mechanism of tracheoesophageal shunt speech after total laryngectomy, we examined the dynamics and origin of neoglottis in tracheoesophageal shunt speakers. DESIGN: We conducted the videofluoroscopic, strobofiberscopic, and electromyographic studies of the pharyngoesophageal segment in tracheoesophageal shunt photonation. SETTING: Academic referral medical center. PATIENTS: Twenty-five tracheoesophageal shunt speakers were examined. RESULTS: Videofluorescopic and fiberscopic examinations showed two bulges in the pharyngeoesophageal segment. The upper bulge was revealed to be the sound source of tracheoesophageal shunt speech by the stroboscopic examination; anteroposterior and undulating regular movements were observed. Electromyographic study elucidated the contribution of muscle contraction to the two bulges; the upper bulge is formed by the thyropharyngeal muscle, whereas the lower bulge corresponds to the cricopharyngeal muscle. CONCLUSION: The neoglottis was considered to be formed by the stenotic portion due to thyropharyngeal muscle contraction and mucosal vibration due to expiratory airflow. This new understanding of the phonatory mechanism will be indispensable in the treatment of cases with failing shunt speech. PMID- 8198789 TI - Nasal reconstruction with conchal cartilage. Correcting valve and lateral nasal collapse. AB - OBJECTIVE: To analyze the causes and the subsequent management of a collapsed valve and lateral nasal wall. The causes, including both predisposing anatomy and the surgical contributions, are presented. DESIGN: Analysis of consecutive patients with lateral nasal wall collapse corrected surgically with autogenous conchal cartilage grafts. PATIENTS: Fifty-six patients (37 women and 19 men; age range, 19 to 71 years) with nasal wall collapse were operated on. Forty-one of these patients had undergone at least one previous nasal procedure. The collapse of the nasal wall as a result of senescence was repaired in 13 patients. Two instances of nasal collapse were thought to be due to trauma. Forty-five patients had bilateral involvement. RESULTS: All 56 patients showed subjective improvement in nasal airway breathing. Rhinomanometry was performed in 24 patients and documented the improvement in all 24. Fifty-three patients noted an improvement in the appearance of their noses. Minimal morbidity was noted and no major complications were seen. Follow-up ranged from 18 months to 13 years. CONCLUSION: Surgery is very beneficial in cases of severe nasal collapse. This major functional complication warrants this major surgical reconstructive procedure and, as the results of this study demonstrate, predictable positive results with little morbidity and no major complications are possible. PMID- 8198790 TI - Imaging quiz case. A case of lumbar abscess as a new otologic complication. PMID- 8198791 TI - Pathologic quiz case. Adenovirus infection of the adenoids. PMID- 8198792 TI - The endoscopic approach to the pituitary gland. PMID- 8198793 TI - Sensorineural hearing loss and nail patella syndrome. PMID- 8198794 TI - Increasing evidence that the myoepithelial cell is the actual ancestor of pleomorphic adenoma of the salivary gland. PMID- 8198795 TI - Otologic complaints. PMID- 8198796 TI - Subcranial approach. PMID- 8198797 TI - Radiotherapy vs total glossectomy with laryngeal preservation for oropharyngeal carcinoma. PMID- 8198798 TI - Surgical treatment of obstructive sleep apnea. PMID- 8198799 TI - Ethyl alcohol induced skin temperature changes evaluated by thermography. Preliminary results. AB - The authors have investigated the validity of thermography in the study of ethyl alcohol induced hand blood flow changes in normal subjects before and after a standard meal. The superficial temperature changes of the hand of ten healthy subjects, 7 males and 3 females, 25-40 years old, were recorded in 4 conditions: a) on an empty stomach, b) after ingestion of a standard dose of ethyl alcohol (25 cc of whisky at 40%, corresponding to 10 g of alcohol), c) after a standard meal (1200 Kcal), d) after a standard meal and a standard dose of alcohol. Three male subjects were not drinkers. Arterial blood pressure and ECG were monitored during the different phases of the experiment. Results show a typical time course of the hand temperature in response to intake of alcohol, stronger in fasting non drinkers subjects. Our results confirm the valuable role of thermography in the study of alcohol-induced calorigenic effects. PMID- 8198800 TI - Morphology of adult white donkeys of Asinara. AB - The phenotype of the Asinara white donkey has the following somatic characteristics: white coat, pink skin and glabrous areas, straight profile, body not very rounded on account of relatively slight muscular development, large head, eyes with irises of a pink-blue colour, short thin neck, not very pronounced withers, straight, average length dorsolumbar region, prominent angular rump higher than the withers, short chest, wide hind quarters, well developed abdomen, short sturdy limbs, light-coloured hooves. The somatometric measurements and the zoometric indexes show small-sized subjects with a hardy bone structure, of compact build with morphological homogeneity between the sexes. The donkeys are of the mesomorph type, more developed lengthwise than in height. PMID- 8198801 TI - One-week test-retest reliability of spinal and cortical somatosensory evoked potentials by tibial nerve stimulation. AB - Spinal (Th12) and cortical somatosensory evoked potentials by right and left posterior tibial nerve stimulation at the ankle were performed in 20 healthy volunteers (10 females and 10 males) aged 23-50 years. The procedure was repeated after one week to assess the reliability of the parameters and to establish upper normal variability limits. Reliability was measured by the intraclass correlation coefficient and was excellent for all absolute latencies and at least good for amplitudes and for the spinal-cortical conduction time. Upper variability limits were calculated using a method based on the within-subject mean square, which can be also applied in the case of more than two repetitions. PMID- 8198802 TI - Cytodifferentiation of the notochord in early chick embryo related to the development of the axial and paraxial structures. AB - The cytology of the notochord was investigated by means of L.M. and T.E.M. in fifty chick embryos from the 7th HH stage to hatching, at different levels of the longitudinal axis and at different levels in each somite. The cytodifferentiation of the notochord was compared with the one of the surrounding axial and paraxial structures (neuro-epithelium and somites). Close segmental relations among notochord, neural groove and sclerotome, i.e. reciprocal contacts of cell processes and filopodia, where observed in 7-9 HH stages embryos. During the following stages in the notochordal cells signs of secretory activity are detectable, but at the same time degenerative changes are evident and they will increase up to the total regression of the notochord. These morphological observations seem to suggest the presence of reciprocal morphogenetic influences among notochord, neuro-epithelium and sclerotome, only before the 9th stage, rather than a determinant role of the notochord in the surrounding structures at later developmental stages. PMID- 8198804 TI - In vivo experimental models on the evaluation of haemoperfusion. AB - We described some experimental models that were performed in rabbits and in swine in order to evaluate the efficacy of haemoperfusion treatment in hypochloremic alkalosis, uraemia and cytotoxic drug poisoning. In all the models, an extracorporeal circuit was used constituted mainly by a hematic sampling line and a cartridge, containing an anion exchange resin. Access to the blood stream was achieved by isolation and catheterization of the vessels either of the neck or of the leg, or both. The experimental model for the evaluation of haemoperfusion in hypochloremic alkalosis was carried out in rabbits by a pyloric stenosis because its size and weight are similar to new-born humans and its stomach is a simple monogastric one. The hypochloremia and alkalosis were achieved in only 4 hours. The other two experimental models were carried out in pigs because, in these cases, it was better to choose a large size animal with a nutritional similarity to humans, and with the capability to produce a stable chronic renal failure. The pigs were submitted to a bilateral ureter ligature to create a chronic renal failure or to a bilateral renal vessel ligature to avoid the physiologic precipitation of some drugs in renal tubules. PMID- 8198803 TI - Studies on renal function in healthy women with different degrees of induced potassium depletion. 3) Effective roles of prostanoids and angiotensin II in hypokalemic renal dysfunction. AB - By using two similar dietary and pharmacological patterns of potassium depletive treatment, two experimental groups--KD2 (n = 6) and KD3 (n = 6)--with cumulative potassium deficit not significantly different, were obtained. The basal values of plasma potassium concentration and PRA, as well as the expression of renal hypokalemic dysfunction were not significantly different. Paired studies in the absence and presence of indomethacin (KD2 group) or enalapril (KD3 group) were performed. The aim of the research was evaluation of the effective roles of prostanoid and angiotensin (AT) II systems in renal hypokalemic dysfunction. The results show that: 1) AT II and cortical vasodilating prostanoids exerted opposite effects on the preglomerular arteriolar tone; 2) medullary prostanoids antagonized the vasopressin effects. Therefore, in potassium depletion the decreased synthesis of cortical and medullary prostanoids, in the face of the increased generation of AT II, contributed to reducing the glomerular filtration rate and facilitate the expression of vasopressin action. These components of the renal hypokalemic dysfunction probably exert a protective role with regard to the urinary chloride and potassium losses. PMID- 8198805 TI - Scanning electron microscopy, chemical and histologic analysis in human periarthritic shoulder biopsy. AB - In the present study biopsies were analyzed, taken from the left shoulder of a patient who, according to the radiological diagnosis, was suffering from calcific periarthritis. In both optical and electronic microscopy the mineralogical observations showed crystalline aggregations, while the chemical analysis, carried out with an Edax EDS spectrophotometer, confirmed the presence of Ca and P in them, in the ratio typical of biological apatites. The histological observations clearly indicate a change in the metabolism of the tissues present. In the samples observed the damage to the muscular tissues is easily seen while the connective tissue, though apparently less compromised, shows the presence of numerous calcifications whose damage cannot be revealed solely through histologic observations. The authors, linking the structural histologic alterations observed to the presence of hydroxyapatite granules as well as to the patient's painful symptoms, believe all these observations are the result of a chronic process. PMID- 8198806 TI - Simultaneous evaluation of vitamins A and E in human plasma by normal phase HPLC. AB - The production of toxic oxidants such as H2O2; OH. and O2.- which follows aerobic metabolism is highly enhanced in aging, alcohol consumption and in a variety of degenerative diseases including neoplasias. Among the different antioxidant agents that in human organisms counterbalance the oxidative stress, which damages lipid, protein and DNA, are included beta-carotene, alpha-tocopherol, glutathione, ascorbate, ubiquinol and specific enzymes such as superoxide dismutase, catalase and glutathione peroxidase. In particular, vitamins A and E are the most important lipid-soluble antioxidants in human tissues protecting polyunsaturated fatty acid from peroxidation. In this paper we report an improved method, obtained after modification of a normal phase HPLC method, which allows the simple and rapid simultaneous evaluation of vitamins A and E in plasma. The separation of vitamins is achieved by eluting the HPLC column with a linear gradient from 1 to 5% isopropanol in n-hexane. The eluate is simultaneously monitored by U.V. and fluorescence detection to identify and quantify vitamins A and E, respectively. PMID- 8198807 TI - Some blood parameters of water buffalo in different physiological conditions. AB - The Authors have studied the changes of GOT, GPT, ALP, CPK and Se in buffaloes under different physiological conditions (age, diet, different pre and post partum times). 99 adult buffaloes were classified in 8 groups on the basis of different pre, post partum time intervals. Moreover, other 39 animals were divided into 4 groups: A = 60-90 day old animals, fed with reconstituted milk supplemented with Vit E; B = same age, fed with maternal milk; C = 6-8 month old animals; D = 12-18 month old animals. In the various classes of animals blood ALP, GPT, GOT, CPK and Se were monitored. Results showed that the high variability in blood activity of the studied enzymes suggest that in establishing their reference values the physiological condition of the subject and the time interval from the parturition must be taken into account. The fact that Se was not detectable in many pregnant animals suggests that the prevention of myodistrophy in buffalo calves must be effected in prenatal epoch. PMID- 8198808 TI - Effect of inducers on the activity of glutathione S-transferase and other enzymes of the glutathione pathway in cultured human keratinocytes. AB - Known inducers of the hepatic glutathione (GSH) S-transferases were tested at the limits of their solubility as inducers of the enzyme in cultured human keratinocytes. Neither phenobarbital, trans-stilbene oxide, propylthiouracil, nor butylated hydroxyanisole increased GSH S-transferase activity or led to the appearance of alpha- or mu-forms of the enzyme, as judged by Western blotting. Only the pi-form of the enzyme was found before and after all treatments. Thus, the enzyme is not inducible in keratinocytes. However, 4 mM propylthiouracil did lead to a 50% increase in GSH reductase activity, and phenobarbital at 4 mM completely abolished GSH peroxidase and GSH reductase activity and led to a significant loss of viability. PMID- 8198809 TI - Metabolism of ethyl 4-aminobenzoate in the isolated single-pass perfused rabbit ear. AB - Isolated rabbit ears were single-pass perfused with a protein-free Tris buffer solution. Ethyl 4-amino[U-ring-14C]benzoate or 4-amino[U-ring-14C]benzoic acid was applied to the epithelial surface in isopropyl myristate, or perfused arterially. Metabolites in the effusate were extracted and separated by high performance liquid chromatography. Five metabolites were separated from ethyl aminobenzoate and identified as aminobenzoic acid, or acid-labile conjugates from either substrate. Their chemical structure has not yet been established. One metabolite, perhaps a glycolic acid N-conjugate of ethyl 4-aminobenzoate, was found at about 100 times higher concentration after arterial than after dermal drug application, indicating that the quantitative metabolic patterns in skin differ depending on whether the xenobiotic reaches the enzymes of the skin by cutaneous absorption or by the blood circulation. The metabolite pattern of the skin was compared with that from rabbit or rat liver cell preparations. PMID- 8198810 TI - Increased superoxide anion production in dermal fibroblasts of psoriatic patients. AB - We studied the superoxide anion activity of psoriatic and normal dermal fibroblasts in culture. Superoxide anion production was measured by the technique of Pick and Mizel in fibroblasts cultured from biopsies of involved and uninvolved skin of patients with psoriasis and from skin biopsies of normal controls. Our results show that the liberation of superoxide anion was significantly increased (p < 0.001) in fibroblasts obtained from involved areas of skin (5.58 nmol O2-/10(6) cells/50 min) and also from uninvolved skin (p < 0.01) (4.60 nmol O2-/10(6) cells/50 min) of psoriatic patients, compared to controls (2.25 nmol O2-/10(6) cells/50 min). The increase in superoxide anion liberation was 100 and 150% in uninvolved and involved psoriatic fibroblasts, respectively. This suggests an important role for dermal fibroblasts in the inflammatory mechanism of psoriasis. PMID- 8198811 TI - Ultrastructural localization and quantification of extracellular calcium binding sites in mouse vibrissa and human scalp follicles. AB - The purpose of these experiments was to determine if an extracellular calcium binding site gradient is evident in freshly dissected or cultured mouse vibrissa and human scalp follicles and to measure possible drug effects on this gradient. Mouse vibrissae were cultured with or without either minoxidil or pinacidil, and human scalp follicles were cultured with or without epidermal growth factor. Anagen vibrissa and scalp follicles were dissected and placed in culture for 4 h to 4 days, then fixed in a solution containing lanthanum chloride and prepared for either quantitative energy-dispersive X-ray microanalysis (X-ray) or qualitative transmission electron microscopy (TEM). Since lanthanum has a high charge density it displaces Ca2+ ions from anionic binding sites. TEM analysis revealed extensive accumulation of electron-dense lanthanum deposits in the intercellular compartment of differentiating cells in the hair shaft and inner root sheath in the apex of the follicular bulb. Sparse lanthanum precipitate was observed in the intercellular space of the proliferative cells at the base of the bulb. This gradient of lanthanum precipitate was evident in both freshly dissected and cultured vibrissa and scalp hair follicles, irrespective of treatment with drugs that grow hair or epidermal growth factor. X-ray microanalysis indicated that percent by weight of lanthanum was markedly higher in the apex compared to the base of the follicular bulb in vibrissa and scalp follicles. These qualitative and quantitative data demonstrate that an extracellular calcium binding site gradient exists in cultured vibrissa and scalp hair follicles, and that this gradient is not significantly affected by hair growth altering drugs including minoxidil or pinacidil, and epidermal growth factor. PMID- 8198812 TI - Feasibility of measuring the bioavailability of topical ibuprofen in commercial formulations using drug content in epidermis and a methyl nicotinate skin inflammation assay. AB - A method has been developed which simultaneously compares the inhibition of an inflammation induced by a methyl nicotinate assay with the concentration of drug in the human epidermis determined in vitro following topical application of two 10% ibuprofen formulations. The bioavailability of drug from commercial gel and emulsion was assessed after the application of various doses (3, 6 and 12 mg/cm2) and an application time of 0.5 h at two time points: 0.5 and 24 h (only with the 12 mg/cm2 dose) after the removal of the non-steroidal anti-inflammatory drug (NSAID) from the skin. In parallel, we assessed the epidermal concentration of the drug in vitro and evaluated the anti-inflammatory effect of the topicals in vivo. A correlation (r = 0.9603, p < 0.001) between the amount of drug in the epidermis expressed as micrograms per milligram of epidermal protein and the corresponding inhibition of the inflammation was observed. Increasing the amount of drug in the epidermis correlated with an increased inhibition of the inflammation. The gel formulation released more drug to the skin and produced a greater anti-inflammatory effect. Topical NSAID concentration in treated skin can therefore be determined and correlates well with the resulting pharmacodynamic activity. This approach will likely have utility in optimizing topical NSAIDs. PMID- 8198813 TI - Does salicylic acid increase the percutaneous absorption of diflucortolone-21 valerate? AB - The percutaneous absorption of diflucortolone-21-valerate (DFV) and its effect on the pituitary adrenal system were investigated during large skin area treatment (20 g ointment twice a day for 8 days) of two groups of healthy volunteers with Nerisona and Nerisalic ointment, respectively. Plasma levels of diflucortolone, cortisol and dehydroepiandrosterone (DHEA) were measured in both groups whereas plasma levels of salicylic acid were measured additionally in volunteers treated with Nerisalic. No differences, neither in percutaneous absorption of DFV nor in effects on cortisol and DHEA were found between the two treatment groups. There was a slight reduction in cortisol levels under both treatments, but the circadian rhythm was not disturbed. Mean salicylic acid plasma levels under high dose topical Nerisalic treatment were about 50-fold below levels where toxicity may be expected. PMID- 8198814 TI - Evaluation of phototoxic and photogenotoxic risk associated with the use of photosensitizers in suntan preparations: application to tanning preparations containing bergamot oil. AB - Bases for the elaboration of a standardized protocol are proposed for studying phototoxic effects of skin tanning preparations containing photosensitizing agents. The experimental procedure includes in vivo phototoxicity tests, evaluation of the photogenotoxic risk and determination of the photosensitizer concentration in plasma after topical application. This procedure was carried out with tanning preparations containing a well-known photosensitizer, 5 methoxypsoralen, as a component of bergamot oil. The whole study has been performed using topical application of the commercial suntan product, i.e. containing the sunscreens and all other components. Whereas the exposure to solar simulated radiation never triggered any phototoxic response, a photosensitizing effect was observed for skin type I volunteers exposed to high doses of ultraviolet A. The transepidermal penetration resulted in a 5-methoxypsoralen concentration of 1-4 ng/ml in the suction blister fluid. The photogenotoxicity of this suction blister fluid containing 5-methoxypsoralen and also other ingredients of the tanning preparation was assayed on yeast cells and was found to be rather low. 5-Methoxypsoralen was also detected in plasma after repeated applications but at low concentrations (about 1 ng/ml) which do not present a potential risk for systemic ocular effects. PMID- 8198815 TI - 5-Lipoxygenase activation in psoriasis: a dead issue? AB - It has been suggested in the literature that 5-lipoxygenase activation may be an important pathological event in psoriasis and that 5-lipoxygenase inhibitors may thus have some beneficial therapeutic effect in this disease. This is because (1) neutrophil activation is a prominent feature of the disease, (2) leukotriene B4 is a potent chemotactic agent for neutrophils and is present in psoriatic lesions, (3) 5-lipoxygenase is present in human epidermis, (4) inhibition of 5 lipoxygenase may affect the disease. These concepts are questioned, and in particular it is suggested that (1) the leukotriene B4-like material found in psoriatic skin has never been shown to have the correct stereochemistry to indicate that it is 5-lipoxygenase derived, (2) there is no convincing evidence for the presence of the 5-lipoxygenase enzyme in human skin, (3) drugs purported to have some benefit in psoriasis through 5-lipoxygenase inhibitory mechanisms act through other mechanisms and (4) selective leukotriene biosynthesis inhibitors have no therapeutic utility in psoriasis. It is concluded that 5 lipoxygenase activation does not play a significant role in the pathology of psoriasis and therefore selective leukotriene biosynthesis inhibitors would have no significant role in the treatment of this disease. PMID- 8198816 TI - Quantitative evaluation of drug-induced erythema by using a tristimulus colour analyzer: experimental design and data analysis. AB - Pulsed-light reflectance using the Minolta Chroma Meter CR-200 was evaluated as a quantitative method for the noninvasive assessment of drug-induced erythema on the flexor surface of the forearm. Nicotinate esters were used as model vasodilators. Several parameters derived from the data were analysed using analysis of variance (ANOVA) and Tukey's multiple range tests appropriate for the study designs used. The effects of varying concentrations of methylnicotinate and of different nicotinate esters were found to be statistically significant. This non-invasive technique was found to be particularly useful in ranking the cutaneous responses elicited by the topical application of increasing concentrations of methylnicotinate in a single subject, as well as in a group of 6 volunteers. PMID- 8198817 TI - Spiral CT of the liver: current applications. AB - Spiral CT allows rapid imaging of the liver resulting in improved contrast dynamics compared with conventional CT techniques. Improved lesion detection has been shown with spiral CT by using overlapping reconstruction intervals and by eliminating respiratory misregistration. Vascular and parenchymal abnormalities, including portal venous thrombosis or cirrhosis with development of collateral vessels, are readily appreciated using spiral technique. Combining spiral CT and portography enhances lesion detection by maintaining high levels of hepatic contrast enhancement for the duration of the liver scan. PMID- 8198818 TI - Spiral CT of the pancreas. AB - Spiral CT technology now represents the gold standard in the evaluation of known or suspected pancreatic pathology. For both neoplastic and inflammatory diseases of the pancreas, spiral CT offers many unique advantages over conventional dynamic CT scanning. This article reviews the basic technique and applications of spiral CT in evaluation of the pancreas, with emphasis on its specific advantages. PMID- 8198820 TI - Neuroradiological applications of spiral CT. AB - Spiral CT is a recent technique in which a patient is scanned while being drawn through the CT gantry, resulting in the generation of a continuous volume of cross-sectional data. Vascular structures can be imaged selectively given an appropriate delay after injection of intravenous contrast, and the images can be reconstructed in all planes. This technique provides an accurate method for the noninvasive evaluation of the carotid arteries and intracranial vasculature. This article discusses the utility of this technique in the determination of carotid stenosis and intracranial aneurysms. PMID- 8198819 TI - Three-dimensional spiral CT angiography of the abdomen. AB - Spiral CT angiography is a technical innovation in vascular imaging that can produce spectacular three-dimensional reconstructions of the abdominal vessels and organs using modified CT scanning techniques. Rapid volume data acquisition allows contrast material to be imaged in the arterial or venous phase. CT reconstruction in cross-sections avoids superimposition of overlying structures. The combination of these features allows spiral CT angiography to produce extraordinary images of the abdominal vasculature and organs. This review outlines fundamental techniques in spiral CT angiography and summarizes our initial clinical experience at Stanford University Medical Center. PMID- 8198821 TI - Pediatric craniospinal spiral CT: current applications and future potential. AB - Spiral CT has a definite role in pediatric neuroimaging. It is fast and offers relatively artifact-free planar and three-dimensional reconstructions. It also provides dynamic vascular phase imaging, a significant decrease in radiation and contrast media requirements, and a potential decrease in sedation while still producing good diagnostic image quality. The complete role of spiral CT angiography in pediatric neuroimaging is, as yet, incompletely explored, but potentially is very useful in the clinical setting of acute head and spine trauma. PMID- 8198822 TI - Technical foundations of spiral CT. AB - In spiral CT, complete anatomical volumes are scanned in continuous fashion typically in 20 to 60 seconds, with the inherent possibility to reconstruct images in arbitrarily fine increments from the volume data set. In this article, we illustrate the basic principles of scanning and image reconstruction in spiral CT and explain the technical prerequisites and limitations. Particular attention is given to considerations of image quality and patient dose. PMID- 8198823 TI - Spiral CT of the thorax. AB - Spiral CT represents a major advance in CT technology. While the patient is advanced through the scanner gantry, continuous data acquisition occurs during suspended respiration eliminating many of the limitations associated with conventional thoracic CT. By eliminating respiratory misregistration and by offering the ability to reconstruct overlapping images at small intervals, spiral CT is advantageous for pulmonary nodule detection. Airway pathology and lesions adjacent to the diaphragm are better visualized with spiral CT and can be displayed in multiplanar or three-dimensional formats. Vascular imaging, including pulmonary embolus detection, is improved by spiral CT because scanning occurs rapidly at the peak of vascular enhancement. PMID- 8198824 TI - Mercury kinetics in a case of severe mercuric chloride poisoning treated with dimercapto-1-propane sulphonate (DMPS). AB - A case of severe mercuric chloride poisoning with clinical signs of mucosal damage of the gastrointestinal tract and anuric renal failure, is presented. The initial whole blood mercury concentration was 14,300 micrograms l-1. This concentration is supposed to be associated with fatal outcome due to multiple organ failure. Because of anuric renal failure, haemodialysis was necessary. Kidney function returned to normal within 10 days. Haemodialysis proved to be ineffective with regard to total mercury elimination. Treatment with DMPS was started because of very severe poisoning, anuric renal failure and optimistic reports on the "new" chelating agent 2,3-dimercapto-1 propanesulphonic acid (DMPS) in mercury poisoning. DMPS was administered by parenteral route initially and was continued thereafter by oral route, until whole blood and urine mercury concentrations had decreased below a level considered as toxic. Except for a temporary pruritic erythema of the skin, no side effects of DMPS treatment were observed. The clinical course was mild, despite continuing high whole blood mercury concentrations. Recovery was uneventful and complete. DMPS treatment, administered by intravenous and oral route, was shown to be an effective alternative for BAL in life-threatening mercuric chloride intoxication. The pharmacokinetic data presented in this case report suggest that non-renal mercury clearance may considerably exceed renal mercury clearance. PMID- 8198825 TI - Current knowledge of mechanisms of carcinogenicity: genotoxins versus non genotoxins. PMID- 8198826 TI - A five year review of fatal self-ingested overdoses involving amitriptyline in Edinburgh 1983-'87. AB - One hundred and twelve cases of fatal self-ingested overdoses were investigated in the Forensic Medicine Unit of the Department of Pathology of the University of Edinburgh in the period 1983-'87 (inclusive). Of these, 24 cases involved amitriptyline as either the sole agent or in combination with another drug, the most common of which was ethanol. The mean age of the latter group was 43 years with a marked female preponderance. The social history was documented with six out of the 24 cases living alone and five out of the 24 cases divorced. The number previously referred for psychiatric treatment and the number of cases where over 100 tablets of the drug had been prescribed at any one time (where known) was recorded: eight out of 24 cases. The fact that amitriptyline was by far the commonest of the tricyclic antidepressants to be encountered in a fatal overdose situation raises the important question of the prescribing of amitriptyline as a first line therapy in mental depression. PMID- 8198827 TI - Increased incidence of DNA double-strand breaks and anti-ds DNA antibodies in blood of workers occupationally exposed to asbestos. AB - Asbestos, proven to be carcinogenic in humans and animals, is reported to have no genotoxic effect. Asbestos workers have an increased risk of lung cancer, mesothelioma, and other tumours. Earlier findings showed that crocidolite can induce DNA strand breaks in cultured rat embryo cells as assessed by nick translation. We investigated DNA double-strand breaks in white blood cells (WBC) of ten workers occupationally exposed to asbestos. According to our results, obtained with neutral filter elution, individuals who had been exposed to asbestos fibres showed two to four times more DNA double-strand breaks (dsb) in white blood cells than ten non-exposed persons. The induced DNA fragments are of about 250 kb (compared to chromosomal DNA of Saccharomyces cerevisiae standard marker). Using additionally the chromosomal DNA protective method of agarose plugs, DNA fragments in the range of 200 to 1000 kb have been found in the white blood cells of the same ten workers occupationally exposed to asbestos. In the white blood cells of non-exposed subjects no DNA fragments could be detected with this method. Compared to 51 non-exposed persons, elevated anti-ds DNA antibody concentrations were found in ten workers occupationally exposed to asbestos. The fact that workers occupationally exposed to asbestos have distinctly more double strand breaks and anti-ds DNA antibodies could mean that an increased incidence of DNA-fragments may be an important indicator in the chronic effect of asbestos associated carcinogenesis. Apparently, the chronic effects of asbestos observed here do not seem to be identical with that of previously reported acute in vitro effects. PMID- 8198828 TI - The teratogenic metabolites of vitamin A in women following supplements and liver. AB - Ten healthy female volunteers were given 5 doses of retinol as the palmitate; 50 and 150 mg retinol as an oral supplement, 50 and 150 mg as fried calf liver (50 and 150 g) and 3, 9 or 30 mg by intra-muscular injection. Plasma concentrations of retinyl palmitate were higher after 50 mg retinol given as an oral supplement compared with 50 mg as liver; there was no significant difference between the 150 mg doses. Plasma concentrations of retinol showed only small increases. The peak plasma concentrations (Cmax) of all-transretinoic acid, the principal teratogenic metabolite of retinol, and the area under the concentration-time curve (AUC) were up to 20-times higher after supplements compared to the same dose as liver. Plasma concentrations of all-trans-4-oxo-retinoic acid, 13-cis-retinoic acid and 13-cis-4-oxo-retinoic acid showed smaller differences between supplements and liver. Intra-muscular administration of 30 mg retinol gave retinyl palmitate concentrations similar to those found after the oral doses but did not increase circulating concentrations of the acid metabolites. Based on the formation of all trans-retinoic acid, liver and supplements are not of equivalent teratogenic potential. Advice to pregnant women on the consumption of liver based on the reported teratogenicity of vitamin A supplements should be reconsidered. PMID- 8198829 TI - The role of flumazenil in the management of patients with acute alteration of mental status in the emergency department. AB - There are a few case reports which suggest that flumazenil can be used as a diagnostic tool in coma of unknown aetiology but no large scale studies have proved its efficacy and cost-effectiveness. Fifty five patients with acute alteration of mental status of unknown aetiology were enrolled prospectively during a time period of one year. Flumazenil was injected intravenously in a regimen of 0.3 mg in the first minute followed by alternate 0.2 mg, 0.3 mg doses every minute until a total dose of 1 mg was given or until the patients responded. Patients were divided into two groups based on their response to flumazenil: Group 1, responders and Group 2, non-responders. The hospital stay was shortened significantly and interventional procedures, such as CT of brain and endotracheal intubation, were rendered unnecessary in several patients in Group 1. The Group 1 patients had a more favourable outcome than that of Group 2. We concluded that flumazenil may serve as a useful tool in diagnosis and management of carefully selected patients with acute alteration of mental status. PMID- 8198830 TI - A physiologically based mathematical model of dermal absorption in man. AB - A sound understanding of the mechanisms determining percutaneous absorption is necessary for toxicological risk assessment of chemicals contacting the skin. As part of a programme investigating these mechanisms we have developed a physiologically based mathematical model. The structure of the model parallels the multi-layer structure of the skin, with separate surface, stratum corneum and viable tissue layers. It simulates the effects of partitioning and diffusive transport between the sub-layers, and metabolism in the viable epidermis. In addition the model describes removal processes on the surface of the skin, including the effects of washing and desquamation, and rubbing off onto clothing. This model is applied to data on the penetration of the herbicide fluazifop-butyl through human skin in vivo and in vitro. Part of this dataset is used to estimate unknown model parameter values and the remainder is used to provide a partial validation of the model. Only a small fraction of the applied dose was absorbed through the skin; most of it was removed by washing or onto clothing. The model provides a quantitative description of these loss processes on the skin surface. PMID- 8198831 TI - Efficacy of 4-methylpyrazole in ethylene glycol poisoning: clinical and toxicokinetic aspects. AB - Potentially fatal ethylene glycol intoxication in an adult with normal renal function was treated with 4-methylpyrazole administered three hours after the incident occurred. The plasma ethylene glycol concentration was 3.5 g l-1 on admission. The metabolic acidosis present on admission resolved within four hours, and the subsequent clinical course was uneventful. The apparent plasma half-life of ethylene glycol was 16 h and the mean renal and plasma clearances of ethylene glycol were 24 and 25 ml min-1, respectively. These results support the hypothesis that complete blockade of hepatic metabolism of ethylene glycol is achieved by 4-methylpyrazole. The only side-effect observed as a result of treatment was a transient slight increase in serum transaminase activity. PMID- 8198832 TI - Atrial natriuretic polypeptide (ANP)-immunoreactivity and specific atrial granules in cardiac myocytes of stroke-prone spontaneously hypertensive rat (SHRSP). AB - The distribution of atrial natriuretic polypeptide (ANP) and atrial specific granules in the myocytes of the atria and ventricles of an experimental animal model, stroke-prone spontaneously hypertensive rats (SHRSP) and a control, Wistar Kyoto rats (WKY), was examined using immunocytochemical and electron microscopic techniques. In the atria of both SHRSP and WKY, ANP-immunoreactivity was recognized in the perinuclear regions of essentially all cardiac myocytes. In the ventricles of WKY, ANP-immunoreactivity was hardly seen except for the impulse conducting system. However, in the ventricles of SHRSP, almost all cardiac myocytes possessed immunoreaction products which were scattered evenly throughout the cytoplasm; this distribution pattern differed from that of the atrial wall of this strain. PMID- 8198833 TI - Immunocytochemical demonstration of cytoskeletal proteins in seminiferous tubules of adult rams and bulls. AB - The immunohistochemical localization of actin, vimentin and tubulin in adult ovine and bovine seminiferous tubules was studied at both the light and electron microscopical levels, using an improved methodical protocol. alpha-smooth muscle actin and structural F-actin were found to be present in myoid peritubular cells. Structural F-actin also occurs in Sertoli cells at three localizations; 1) As part of the Sertoli-Sertoli-junctions in a stage-dependent manner; 2) where Sertoli cells are in contact with spermatocytes; 3) in ectoplasmic specializations lining the recesses that support elongating spermatid heads. Vimentin is localized in peritubular myoid and fibroblastic cells and in Sertoli cells. In the latter, vimentin is concentrated in a perinuclear position. alpha tubulin is observed in the cytoplasm of spermatogonia, in axonema and manchette of spermatids and in Sertoli cells with their abundant microtubules. Since the alpha-tubulin reaction decorates even the narrowest lateral and apical cell processes, it is an excellent marker to study changes in Sertoli cell shape and size during the seminiferous epithelial cycle in rams and bulls. PMID- 8198834 TI - Oblique smooth muscle bundles between the circular and longitudinal muscle layers in the canine proximal colon. AB - The region between the longitudinal and circular muscle layers of the canine proximal colon was investigated by light and electron microscopy. Unique smooth muscle bundles, referred to as "oblique" muscles, were arranged in branching/anastomosing bundles, forming a network intermeshed with the nerve plexus and vasculature. These smooth muscles were concentrated along the ganglia and primary connectives of the myenteric plexus, thus showing a periodic distribution roughly corresponding to that of the ganglia. The oblique smooth muscle bundles bridged the distance between the circular and longitudinal muscle layers and blended into the inner aspect of the longitudinal muscle layer and the outer aspect of the circular muscle layer. A few oblique muscle cells occurred within the sheath of the ganglia and primary strands, i.e., perineurium. Oblique muscles may serve to electrically couple the circular and longitudinal muscle layers, thus explaining the synchronous electrical activities of these muscles. It is possible that the pacemaker activity in the myenteric region is generated by these muscle cells. Oblique muscles may also serve to protect nerve elements and the vasculature from the mechanical stress of peristalsis. PMID- 8198835 TI - Three-dimensional structures of the neck region of the hamster spermatozoa in the caudal epididymis. AB - Three-dimensional structures of the capitulum and first mitochondria in the neck region of the hamster spermatozoa, were observed with transmission (TEM) and scanning electron microscope (SEM). Some capitula revealed a variable contour even in the caudal epididymis, but most finally developed to form a typical wagonette shape. The final shape of the capitulum is probably produced by the aid of apical protrusion of the right, pyramidal mitochondrium. The right and left first mitochondria were triangular pyramids in contour, while the dorsal and ventral ones were rod-like in shape. The mutual transformations between the capitulum and the first mitochondria are discussed in relation to the completion of the neck region. PMID- 8198836 TI - Electron microscopic observation of the transitional portion in the human eccrine sweat gland. AB - The transitional portion in human eccrine sweat glands was observed by transmission electron microscope (TEM). The transitional portion, consisting of columnar epithelial cells (columnar cells) and basal cells, formed a very short segment about 25 to 50 microns in length. The portion was abruptly connected to the secretory segment, and shifted to the excretory duct without marked ultrastructural changes. The columnar cells were morphologically characterized by small apical vesicles as reported in previous reports. Considering the frequency of the mitosis of the columnar cells, the transitional portion seemed to be one of the areas of cell proliferation in the gland. Basal cells were sparse in the region connecting the secretory segment, but dense near the duct. Basal cells in the secretory segment side of the transitional portion, containing thin microfilament-bundles in the infranuclear cytoplasm, were considered to be immature myoepithelial cells. On its ductal side, however, the basal cells showed morphological profiles similar to ductal peripheral cells. These findings suggest that the differentiation of myoepithelial cells occurs in the transitional portion of eccrine sweat glands. PMID- 8198837 TI - Neuropeptide Y-immunoreactive structures in the telencephalon and diencephalon of the white sturgeon, Acipenser transmontanus, with special regard to the hypothalamo-hypophyseal system. AB - An immunohistochemical study using a streptavidin-biotin method demonstrated the extensive distribution of neuropeptide Y (NPY)-like immunoreactivity in the brain of the white sturgeon, Acipenser transmontanus, with the highest density in the basal telencephalon and diencephalon. Two labeled cell groups were found in the telencephalon, in mediobasal and dorsocaudal locations. Labeled fibers were considerably dense in the ventral area. The epithalamus displayed dense networks of varicose fibers in the ganglion habenulae, but only a few fibers were seen in the organon subcommissurale. In the thalamus, two groups of labeled cells were discerned in the periventricular gray matter: an anteroventral group largely composed of cerebrospinal fluid (CSF)-contacting neurons, and a dorsocaudal group consisting of non-CSF-contacting large neurons. The hypothalamus also contained a number of CSF-contacting neurons in the periventricular areas including the nucleus lobi inferioris, the nucleus lateralis tuberis and the nucleus recessus posterioris. Labeled varicose fibers were closely associated with the hypothalamo hypophyseal complex, the organon vasculosum hypothalami, and the saccus vasculosus. Immunoreactive cells and fibers were also detected in the dorsal region of the adenohypophysis. These results suggest that NPY or a related molecule is involved in the hypothalamic neuroendocrine mechanisms of this primitive bony fish. PMID- 8198838 TI - A morphological study of acute respiratory tract lesions in a lipopolysaccharide instilled rat model. AB - Acute inflammatory reactions in different respiratory regions were studied in a lipopolysaccharide (LPS) instilled rat model. Rats were sacrificed at 1, 2, 4, 8, 12, 24 and 48 h after administration of Escherichia coli LPS to the lumen of the trachea, and changes in the trachea, bronchioles and alveoli were observed by light and electron microscopy. In the trachea, neutrophils were markedly increased in subepithelial connective tissue and between tracheal epithelial cells, from 2 h on, showing a peak at 8 h. The number of tracheal mast cells increased at 4 and 8 h. Different structural features of secretory granules between mast cells in the tracheal epithelium and subepithelium were noticed, and the possible involvement of mast cells in airway acute inflammation is discussed. In the bronchioles, Clara cells showed characteristic morphological alterations. At 8 to 12 h, Clara cells revealed well-developed smooth and rough endoplasmic reticula and many free ribosomes, possibly for enhanced synthesis of secretory substances. Many Clara cells possessed a large apocrine-like protrusion filled with an amorphous substance, likely indicating an apocrine secretion of the cells. At 24 h, Clara cells were observed to take on a pseudostratified arrangement, suggesting enhanced proliferation of progenitor cells and their differentiation into Clara cells. In the alveoli, neutrophils infiltrated alveolar walls and pulmonary venules at 4 h and disappeared at 12 h. Prior to morphological changes in bronchioles and alveolar walls at 2 h, the macrophages with well-developed filopodia and free-ribosomes appeared in alveolar sacs and ducts. They may contribute to histological changes especially at the initial stage of acute inflammation in alveoli. PMID- 8198839 TI - Microcirculatory patterns in human pancreas: supplementary observations of vascular casts by scanning electron microscopy. AB - The blood vascular bed of two human pancreata was replicated partially by arterial perfusion of intentionally reduced amounts of low viscosity methacrylate resin, to be observed with a scanning electron microscope. The findings were compared with those obtained from a pancreas replicated completely by a sufficient amount of resin. Complete replication confirmed our previous findings (MURAKAMI et al., 1992) that many exocrine lobules contained one or more endocrine islets, which preferentially issued insulo-acinar portal vessels continuous with the lobular capillaries. Incomplete replication demonstrated that the casting medium filled blood capillaries in the endocrine islets more promptly than those in the exocrine lobules and secretory ducts. Furthermore, islet containing lobules allowed a more rapid resin flow to the exocrine tissue via the insulo-acinar portal route than did the lobules lacking an islet. Since the resin medium used had the viscosity of blood and was injected under physiological pressure, the results obtained by the incomplete arterial injections are believed to suggest the physiological state of blood flow in the pancreas. PMID- 8198840 TI - Autism: fifty years on from Kanner. AB - It is now 50 years since Leo Kanner first described autism as a distinctive pattern of symptoms in some children with severe developmental problems. Since then the assessment and diagnosis of children with pervasive disorders of development has been refined and much is known about the phenomenology and epidemiology. Autism is a biological disorder of the central nervous system (CNS) of unknown cause. It is associated with a number of organic disorders such as epilepsy and has comorbidity with other psychiatric disorders such as tic disorder. Cognitive abnormalities in social interactions, affect and language are present but there is still debate regarding which of these, if any, is the primary cognitive deficit. Special education and behavioral management has led to modest but important developmental improvement in many children with autism. Autism remains a life-long condition but patterns of symptoms change and skills develop from childhood into adult life. PMID- 8198841 TI - Barriers to safety. PMID- 8198842 TI - Barriers to childhood injury control in New Zealand. PMID- 8198843 TI - Child injury in Brisbane South 1985-91: implications for future injury surveillance. AB - Specific childhood injury types are ranked by occurrence rate for mortality, hospital admission and emergency department attendance. Cases are drawn from the resident population of Brisbane South, 0-13 years of age, for the period 1 July 1985 to 30 June 1991. A total of 47,244 injuries, 7056 admissions and 99 deaths were analysed. The overall mortality rate was 12.6/100,000 per year (95% confidence interval (CI), 10.2-15.3), the overall admission rate was 911/100,000 per year (95% CI, 890-932) and the overall hospital attendance rate was 6013/100,000 per year (95% CI, 5958-6067). A fall was the most frequent injury mechanism for admissions and 65% of attendances involved injury in the child's own home. The surveillance data establish regional variation for childhood injury risk within Australia and identify an unexplained downward trend in head injury that requires further investigation. The future development of injury surveillance in Australia requires simplified coding which can be integrated into new computerized patient management information systems. PMID- 8198844 TI - Aminophylline therapy and cerebral blood flow velocity in preterm infants. AB - Pulsed Doppler ultrasound was used to evaluate the cerebral blood flow velocity (CBFV), in the middle and anterior cerebral arteries in 10 infants before and after the administration of aminophylline (7.5 mg/kg). Mean CBFV, heart rate, blood pressure, oxygen and carbon dioxide tensions were recorded before the loading dose, and then at 1, 2, 6 and 24 h after completion of the infusion. Mean CBFV in the middle and anterior cerebral arteries were 16.8 cm/s and 10.8 cm/s respectively prior to the infusion. There was a significant decrease (P < 0.05) in velocities in both arteries at 1 and 2h post drug therapy, which returned to base values by 6 h, and remained as such at 24 h. The heart rate increased (P < 0.05) after the infusion, while no consistent changes were observed in blood pressure or oxygen tension. Carbon dioxide levels were significantly reduced (P < 0.05) at 2 h. The reduction in CBFV, however, was more than would be expected on the basis of the change in carbon dioxide levels alone, suggesting that other factors may be exerting an influence. While no adverse effects were noted in the infants studied, it is suggested that aminophylline should be used judiciously in sick preterm infants at highest risk from ischaemic brain injury. PMID- 8198845 TI - A medium term follow-up study of patients with hypertrophic pyloric stenosis. AB - A structured questionnaire was sent to the parents of 120 children from a cohort 192, who had undergone a pyloromyotomy for pyloric stenosis at Westmead Hospital during the years 1984-91. Information was gained from 85 children in 82 families regarding gastrointestinal complaints and family history of pyloric stenosis. There were few gastrointestinal problems, no reports of recurrent abdominal pain, but two reports of clinically significant vomiting (2.3%) and one of infantile colic. Of the 85 individuals studied, 21 (24.7%) had a positive family history of pyloric stenosis, a higher frequency than previously reported. PMID- 8198846 TI - Outcome of resuscitated apparently stillborn infants: a ten year review. AB - This study addresses the dilemma of whether to attempt resuscitation of the previously undiagnosed fresh stillborn infant and evaluates factors predictive of survival and long-term outcome. We reviewed the clinical spectrum, immediate complications and long-term outcome of 45 successfully resuscitated apparently stillborn infants (34 term, 11 preterm) who were admitted to the Intensive Care Nursery. Significant obstetric and intrapartum events were identified in 34 (75%) infants while 11 (25%) had no apparent risk factors. Of the 39 infants with neonatal complications, 37 had hypoxic-ischaemic encephalopathy (HIE: Sarnat stage 1 in 5, stage 2 in 15, stage 3 in 17); 12 (27%) had oliguria, 10 (22%) had hypotension, 7 (16%) experienced hypoglycaemia, 4 (9%) had disseminated intravascular coagulopathy (DIC) and 1 (2%) had persistent pulmonary hypertension of the newborn (PPHN). Fourteen infants (31%) died in the neonatal period and four (9%) died during infancy. Risks of death and adverse neurodevelopment were significantly increased in infants with stage 2 or 3 HIE (P < 0.005). Follow-up assessment of 24 of the 27 surviving infants revealed a normal outcome in 15 (63%), severe disability in six (25%), moderate disability in two (8%) and mild disability in one (4%) infant. The positive predictive value of stage 2 or 3 HIE was 70% for mortality and 80% for morbidity. One-third (15/45) of successfully resuscitated apparently stillborn infants were normal at follow-up assessment and the outcome for these infants was predicted with complete accuracy by the stage of HIE present during the neonatal period. PMID- 8198847 TI - Survival of low birthweight infants in central Queensland. AB - The survival of low birthweight infants < or = 2000 g born in the central Queensland area during the years 1979 to 1991 was examined. Five hundred and sixty such infants were either delivered at one of the two Rockhampton obstetric units (Rockhampton Base Hospital and the Mater Misericordiae Hospital) or retrieved from outlying central Queensland areas. Both hospitals had intensive care nurseries capable of ventilation and infants were transferred to tertiary centres only for cardiac or surgical treatment. The study involved all liveborn infants, including those with lethal malformations and all deaths up to the time of discharge. Survival rates were as follows: < or = 500 g 0%, 501 < or = 750 g 30%, 751 < or = 1000 g 51%, 1001 < or = 1500 g 79%, 1501 < or = 2000 g 93%. The survival of Aboriginal infants and outborn infants were found to be essentially the same as the overall group. PMID- 8198848 TI - Well health care and the sudden infant death syndrome. AB - The aim of this study was to examine whether poor attendance at routine antenatal and postnatal 'well child' health services was associated with a higher risk of sudden infant death syndrome (SIDS, or cot death). A nationwide case-control study of SIDS in New Zealand enrolled 485 postneonatal deaths due to SIDS and 1800 control infants who were selected randomly. The risk for SIDS was found to be higher for infants whose mothers attended their first antenatal check later than 3 months into the pregnancy, made fewer antenatal visits, and did not go to antenatal education classes. However, this increased risk was largely explained by high parity, maternal smoking, the mother not being married, mother being < 20 years old at the birth of her first child, and delivery during the winter months. Infants not attending a 6 week postnatal check had an almost three-fold increased risk of SIDS compared with those who did attend (odds ratio [OR] 2.86; 95% confidence interval [CI] 1.93, 4.24). Similarly, infants not attending well child clinics were at increased risk of SIDS (OR 2.75; 95% CI 2.09, 3.62). These differences persisted when adjusted for likely confounders. This study demonstrates that infants who miss child health nurse clinics are those most at risk for SIDS and are those who warrant increased surveillance. PMID- 8198849 TI - The micro-environment of the sleeping newborn piglet covered by bedclothes: gas exchange and temperature. AB - This study followed the thermal and gaseous micro-environment of the newborn piglet sleeping under two levels of bedding insulation. After 1 h in the piglet's thermal comfort zone, the head of each piglet was covered for 2 h with bedding either 12 mm or 21 mm thick. Body temperature rose rapidly, but the arterial gases showed no change in the direction of asphyxia; with the thicker covering PaO2 was unchanged and PaCO2 fell and pH rose. These changes were despite a small rise in environmental PCO2 and fall in PO2 but were also minimized by the piglet's ability to avoid profound hypocapnia by panting at a very low tidal volume. No significant changes in blood gases occurred with the thinner bedding; the temperature rose markedly but more slowly. It is suggested that human babies submerged under bedclothes for any length of time would be more likely to succumb to the effects of hyperthermia than of asphyxia. PMID- 8198850 TI - Communicable disease outbreaks in long day care centres in western Sydney: occurrence and risk factors. AB - We surveyed the directors of all 92 long day care centres in western Sydney to document the occurrence of communicable disease outbreaks during 1992 and to identify risk factors for the occurrence of these outbreaks. A total of 6092 children were enrolled at the centres, of whom 530 (8.7%) were less than 3 years old. Most centres (80.4%) reported at least one outbreak of communicable disease. Diarrhoea was the most commonly reported outbreak type (60 outbreaks), followed by conjunctivitis, head louse infestation and chicken pox (46, 44 and 24 outbreaks, respectively). Chicken pox outbreaks had the largest mean number of cases per outbreak (9.6) and the longest mean outbreak duration (4.4 weeks). Centres with a large total enrollment (50 or more children), those that were open for 12 or more hours each day and those which had commenced operating in 1990 or more recently were generally more likely to report outbreaks, particularly of diarrhoea. The vast majority of communicable disease outbreaks (92.1%) were handled by day-care staff without seeking outside assistance. Day-care centre directors may be unaware of the health services that could help them. We need to work more closely with long day care centres, and to focus preventative efforts on large centres, those open for long hours, and newly opened centres. PMID- 8198851 TI - A practical intervention to address ear and lung disease in Aboriginal primary school children of central Australia. AB - Australian Aboriginal populations have an extremely high prevalence of lung disease and ear disease. In addition to an improvement in socio-economic conditions, implementation of strategies to address the problem, within the limitations of present conditions, is needed. A 5 month trial was conducted to investigate the effectiveness of a school-based intervention programme involving nose blowing, deep breathing and coughing combined with exercise performed daily. This was a community-based trial, designed to give priority to cultural and ethical considerations, to be non-intrusive and to utilize local skills and resources. Results of the trial showed that signs of upper and lower respiratory tract disease and pulmonary function measurements were statistically significantly improved. Hearing levels showed no statistically significant change. The programme met with a good response from children and teachers. This study does suggest that this strategy may help address the existing problems of lung and ear disease in Aboriginal primary school children, providing some immediate benefits within the limitations of the present socio-economic conditions. PMID- 8198852 TI - Lumbar punctures in suspected bacterial meningitis: too many or too few? AB - Children aged 1 month to 14 years admitted to the Royal Alexandria Hospital for Children during a 10 month period with suspected meningitis were studied prospectively. The aims were to determine how often lumbar puncture (LP) was delayed or never done, in relation to the outcome of all children, in order to determine the risks of LP and the risks of not doing LP. Of 218 children with suspected meningitis, LP was performed immediately in 195 (89.4%). Meningitis was diagnosed in 49 of these (bacterial 18, viral 31). No child developed cerebral herniation due to immediate LP. There were 11 traumatic taps and two children required repeated attempts. Lumbar puncture was delayed, but performed at a later time in 17 children, of whom three had proven bacterial meningitis, 1 had presumed bacterial meningitis but no organism was detected and 13 had alternative diagnoses. Six children never had an LP, although ventricular cerebrospinal fluid was obtained from two. Four of these six children had presumptive bacterial meningitis, one had tuberculous meningitis presenting with acute hydrocephalus and diagnosed post-mortem, and one had a very poor neurological outcome and no final diagnosis was reached. Of the 27 children with bacterial meningitis, LP was performed immediately in 18, or two-thirds. There were only minor adverse effects of immediate LP. Delayed LP probably resulted in failure to identify the organism in one child with bacterial meningitis, but did not adversely affect outcome in any child. Of the six children in whom LP was never performed, in only one was no final diagnosis reached.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198853 TI - Impaired increase of prostaglandin E2 in gastric juice during steroid therapy in children. AB - To investigate the aetiology of steroid-induced peptic ulcers in children, prostaglandin E2 (PGE2) release and acid secretion into gastric juice was evaluated in 10 children receiving a corticosteroid before and after injection of pentagastrin. The concentration of luminal PGE2 was measured by radio immunoassay. The basal levels of PGE2 concentration and acid secretion in gastric juice did not differ significantly between the steroid therapy group and control group. After stimulation with pentagastrin, acid secretion increased significantly (P < 0.01) in both groups and PGE2 concentration increased significantly (P < 0.01) only in the control group. Prostaglandin E2 concentration was significantly lower in the steroid therapy group than in the control group 20-40 and 40-60 min after pentagastrin stimulation (P < 0.01 and P < 0.05, respectively). Since PGE2 has a cytoprotective effect on the gastric mucosa, the results of impaired increase of PGE2 in response to increased acid secretion during steroid therapy may indicate causality with the development of steroid-induced peptic ulcers. PMID- 8198854 TI - An outbreak of Pneumocystis carinii pneumonia in children with malignancy. AB - An outbreak of Pneumocystis carinii pneumonia (PCP) in three patients within a 6 week period was reported. Two patients had acute lymphoblastic leukaemia and one had brain-stem glioma. They shared common features of immunosuppression and absence of cotrimoxazole prophylaxis and had been nursed in the same room. The severity of PCP and its response to treatment may be related to the degree of immunosuppression. Because of the morbidity and mortality of PCP, chemoprophylaxis should be given to all at-risk cases. Furthermore, isolation of patients with PCP should be considered in view of increasing evidence of nosocomial transmission. PMID- 8198855 TI - Hypothermia in children with severe neurological disabilities. AB - Four severely disabled children who developed hypothermia during acute illness are described. A central defect in thermoregulation in the hypothalamus is likely, based on clinical observation and limited investigations, as well as similarities to sporadic cases reported in the literature. Disturbance of temperature regulation appears to be a rare complication of major brain injury in children, without necessarily occurring in association with pituitary dysfunction. It is of clinical importance because subnormal temperature may indicate severe sepsis. PMID- 8198856 TI - Dumping syndrome after Nissen fundoplication. AB - Dumping syndrome is infrequently reported in children, but has significant morbidity. It may be difficult both to diagnose and manage. Two children are reported who developed dumping syndrome after Nissen fundoplication. Symptoms occurred soon after the operation and included post-prandial pallor, sweating, lethargy and diarrhoea. Failure to thrive was a prominent feature. Typical biochemical changes included hyperglycaemia shortly after meals, followed by hyperinsulinaemia and reactive hypoglycaemia. Effective treatment was only achieved with continuous enteral feeding. Children undergoing fundoplication should be closely monitored for episodes of hypoglycaemia and unresponsiveness. The incidence of dumping syndrome after fundoplication may be underestimated, particularly in children. PMID- 8198857 TI - Neonatal renal candidiasis. AB - A case is presented of renal candidiasis complicated by obstructive uropathy in a 4 month old infant. Management was successful with surgical decompression combined with peri-operative amphotericin B, followed by 3 weeks of oral ketoconazole and subsequently 6 weeks of oral fluconazole. Fluconazole was substituted for ketoconazole owing to persistent candiduria, and achieved rapid urinary sterilization. Fluconazole is an effective and less toxic alternative to prolonged courses of amphotericin B in the treatment of neonatal renal candidiasis. PMID- 8198858 TI - The gross neglect of child psychiatry. PMID- 8198859 TI - Paediatricians' reports to general practitioners: should parents receive copies? PMID- 8198860 TI - Eucalyptus oil: therapeutic and toxic aspects of pharmacology in humans and animals. PMID- 8198861 TI - Change in measles activity in Australia with the effect on immunization schedules. PMID- 8198863 TI - Medico-legal aspects of birth asphyxia: a paediatrician's perspective. PMID- 8198862 TI - Lactose intolerance in Asian children. PMID- 8198864 TI - Community paediatrics: caring for children better. PMID- 8198865 TI - A national policy on asthma management for schools. The Asthma Special Interest Group, Thoracic Society of Australia and New Zealand. AB - Since asthma is the most common chronic illness in childhood, many of the problems associated with this condition will impact on the child's education. Because of widespread concerns regarding the management of asthma in schools, a subcommittee of the Thoracic Society of Australia and New Zealand, Asthma Special Interest Group, was convened to draw up national guidelines for school staff in order to provide optimal management of asthma in the school setting. We used current medial literature and the clinical experience of the authors who have dealt with children and adolescents suffering from asthma in the hospital, community and school environment. A number of issues had been identified, including: the availability of an asthma first aid kit; correct use of bronchodilator aerosols by puffer and spacer devices; and clear instructions as to when to notify parents and when to call an ambulance to the school.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198866 TI - Molecular biology of HIV: challenges for the second decade. PMID- 8198867 TI - Human immunodeficiency virus type 1 infection of neonatal severe combined immunodeficient mice xenografted with human cord blood cells. AB - In these studies, neonatal C.B-17 severe combined immunodeficient (nSCID) mice were reconstituted with human cord blood leukocytes (hu-CBLs). The resulting hu CBL-nSCID mice contained readily detectable human CD3+ T lymphocytes and CD20+ human B cells, and produced substantial levels of human IgM and IgG (including all subclasses). Human cells persisted in lymphoid organs and peripheral blood for at least 8 weeks, and CD4+ T cells outnumbered CD8+ T cells. Engraftment of human cells in peripheral lymphoid organs and blood was much greater than that seen in adult SCID mice grafted with adult peripheral blood leukocytes (PBLs). Hu CBL-nSCID mice were susceptible to infection with laboratory-adapted and fresh clinical human immunodeficiency virus type 1 (HIV-1) isolates. Following infection with HIV-1, virus could be recovered by the coculture of spleen, lymph node, peritoneal cavity, liver, and plasma samples from hu-CBL-nSCID mice with fresh human peripheral blood mononuclear cells, and proviral copies were detectable following amplification using the polymerase chain reaction (PCR). HIV p24 core antigen levels in hu-CBL-nSCID mouse plasma were consistent with ongoing viral replication and high viral burdens. Rapid CD4+ T cell depletion occurred following infection with laboratory isolates of HIV-1 or a syncytium-inducing clinical isolate, but a non-syncytium-inducing clinical isolate caused expansion of CD8+ T cells, leading to an inversion of the CD4:CD8 ratio with only a transient decrease in CD4+ T cells. These results suggest that the hu-CBL-nSCID mouse system has unique features that mimic certain aspects of pediatric HIV infection, and distinguish it from other animal models of HIV infection, including the related hu-PBL-SCID model. PMID- 8198868 TI - Identification of novel neutralization-inducing regions of the human T cell lymphotropic virus type I envelope glycoproteins with human HTLV-I-seropositive sera. AB - The humoral immune response in sera from 30 human T cell lymphotropic virus type I (HTLV-I)-positive individuals from Martinique in the French West Indies was studied. The subjects were subdivided into those suffering from TSP/HAM and those being asymptomatic. In general, TSP/HAM patient sera seemed to contain more virus specific antibodies than did the sera from the asymptomatic subjects. Three of the 13 TSP/HAM sera and 1 of the 17 asymptomatic sera contained HTLV-I-specific IgM antibodies, whereas 6 and 5 sera, respectively, contained IgA antibodies. By correlating the ability of patient sera to inhibit HTLV-I-induced syncytia with their antibody reactivity in ELISA to 42 synthetic peptides, together corresponding to the entire envelope glycoprotein of HTLV-I, a number of putative neutralizing domains were identified. Eight synthetic peptides representing the regions with the highest coefficient of correlation between neutralizing titer and ELISA reactivity were employed to specifically adsorb potentially neutralizing antibodies, and were also used directly, without sera, in the syncytium-neutralizing test. By those techniques, three novel and two previously described domains that seemed to contain neutralizing epitopes were identified. Two of the novel neutralizing sites resided in the external glycoprotein (gp46) and were contained within amino acids 53-75 and 287-311, respectively, and one was located in the transmembrane glycoprotein (gp21) within amino acids 346-368. Our findings may have implications for the rational design of subunit vaccines for prevention of and/or alteration of the clinical outcome of HTLV-I-related diseases. PMID- 8198869 TI - Human herpesvirus 6 envelope glycoproteins B and H-L complex are undetectable on the plasma membrane of infected lymphocytes. AB - Membrane immunofluorescence analysis of cells infected with either variant (A or B) of human herpesvirus 6 revealed a typical punctate staining, after labeling with several HHV-6-positive human sera or with two monoclonal antibodies directed to gB and gH. Immunoprecipitation studies showed a sharp difference in glycoprotein content in whole-cell extracts versus on the cell surface, suggesting the occurrence of gB in the extracellular virions juxtaposed to plasma membranes. By immunoelectron microscopy, the extracellular virions still attached to the cell surface appeared consistently and specifically labeled, whereas the plasma membrane was always unlabeled, independent of viral variant, antibody, or target cell used. These findings may reflect an atypical maturation pathway of HHV-6, and could have important implications in the control of cellular immune response to HHV-6-infected lymphocytes. PMID- 8198870 TI - In vitro susceptibility of Macaca nemestrina to human herpesvirus 6: a potential animal model of coinfection with primate immunodeficiency viruses. AB - Human herpesvirus 6 (HHV-6), a lymphotropic herpesvirus, has been suggested as a potential cofactor in the acquired immunodeficiency syndrome (AIDS). Previous studies indicate that HHV-6 has a restricted range of susceptible species. In this study, we tested the in vitro susceptibility to HHV-6 of Macaca nemestrina (pig-tailed macaque), a species that has been found to be infectable by human immunodeficiency virus type I in vivo and that develops an AIDS-like syndrome following simian immunodeficiency virus (SIV) infection. Two different HHV-6 isolates (HHV-6GS and HHV-6BA), belonging to the two major HHV-6 variants (A and B, respectively), were employed. Both viruses induced a productive and cytopathic infection in phytohemagglutinin-stimulated peripheral blood T lymphocytes from M. nemestrina. In contrast, only HHV-6BA (variant B) was able to replicate in lymphocytes from Macaca mulatta (rhesus macaque). Moreover, HHV-6GS and SIVsmE660 productively coinfected individual M. nemestrina lymphocytes, resulting in increased levels of SIV replication. Genetic sequences of HHV-6 were not amplified by polymerase chain reaction from peripheral blood mononuclear cells of several adult M. nemestrina, suggesting that these animals, unlike humans, are not commonly infected by HHV-6, or a related virus. Thus, M. nemestrina may represent an optimal animal model system to investigate the in vivo interactions between HHV-6 and the primate immunodeficiency viruses. PMID- 8198871 TI - Passive immunization of cynomolgus macaques with immune sera or a pool of neutralizing monoclonal antibodies failed to protect against challenge with SIVmac251. AB - In the first of two passive transfer experiments, three groups of four macaques were injected intraperitoneally with a normal serum pool, an immune serum pool (pool 1) collected 132-172 weeks postinfection with the 11/88 pool of SIVmac251, or with a pool of four neutralizing monoclonal antibodies (KK9, 17, 54, and 56) raised against gp120 of the 11/88 pool. Sera were given at a dose of 13 ml/kg whereas the MAb pool was given at 30 ml/kg. In a second experiment, a further four macaques were injected with an immune serum pool (pool 2) collected 12 weeks postinfection with simian-grown SIVmac251 at a dose of 19 ml/kg. Animals in both experiments were challenged with SIVmac251 grown in simian peripheral blood lymphocytes. Despite high levels of circulating antibodies in the serum of animals that received either the immune serum pools or the MAbs, all macaques became infected following challenge. The results described are in contrast to a previous report in which passive transfer of sera from animals infected with SIVsm successfully protected against challenge with the homologous virus grown in human PBMCs. Challenge with SIVmac251 grown in simian PBMCs may be the reason for these conflicting results. Nevertheless, the results suggest that in this model the presence of circulating neutralizing antibodies alone does not necessarily confer protection against challenge with SIVmac251 grown in simian cells. PMID- 8198872 TI - Reduced virus load in rhesus macaques immunized with recombinant gp160 and challenged with simian immunodeficiency virus. AB - As a safe alternative to inactivated and live-attenuated whole-virus SIV vaccines, we have evaluated the potential of SIVmac239 gp160 expressed by recombinant vaccinia virus (vSIVgp160) and baculovirus (bSIVgp160) to protectively immunize rhesus macaques against intravenous (i.v.) infection with pathogenic SIVmac isolates. Macaques were immunized with live vSIVgp160 and/or bSIVgp160 protein partially purified from insect cells. The challenge viruses, propagated in rhesus peripheral blood mononuclear cells, consisted of the molecular clone SIVmac239 and another genetically similar, uncloned isolate, SIVmac251. Although antibodies that bind gp130 were induced in all animals following immunization with SIVgp160, neutralizing antibodies were undetectable 1 week prior to virus challenge. These results differ from those for macaques vaccinated with inactivated, whole SIV. All animals became infected after i.v. inoculation with 1-10 AID50 of either challenge virus. For animals challenged with SIVmac251, but not those challenged with SIVmac239, the cell-free infectious virus load in plasma of vSIVgp160-primed, bSIVgp160-boosted macaques was significantly lower than in unimmunized controls at 2 weeks postchallenge. Virus virulence, immunization regimen, and challenge with homologous or heterologous virus are factors critical to the outcome of the study. Immunization with surface glycoprotein may not necessarily provide protective immunity against infection but may reduce virus load. The relationship between reduction in virus load by vaccination and delay in onset of disease remains to be determined. PMID- 8198874 TI - Titration and characterization of two rhesus-derived SIVmac challenge stocks. AB - Simian immunodeficiency virus infection of macaques is a model for human immunodeficiency virus infection of humans. In vivo-titrated stocks of SIV are essential for the utilization of this model for vaccine development. The elicitation of anti-human cell antibodies by some vaccines prepared in human cells and the related protective effects of the vaccine produced in human cells suggest a need for new macaque-derived SIV stocks. Here we describe the titration and characterization of two stocks of SIVmac that were produced in primary rhesus macaque cells. The first virus is SIVmac251, isolated from tissues of macaque 251, and the second is a molecular clone designated as SIVmac239. A 50% rhesus monkey infectious dose (MID50) was titrated for each virus stock by intravenous inoculation. An additional five macaques were inoculated with 10 MID50 of the SIVmac251 stock and were followed for disease outcome. All five monkeys developed antigenemia by 14 days postchallenge. Two of the five monkeys developed strong anti-SIV humoral immunity, whereas three developed little or no humoral immunity. As has been observed previously, the rapidity of disease progression correlated with the lack of a strong antibody response. The three animals with low humoral immunity died within 7 months of challenge, with antigenemia, cachexia, hypoproteinemia, hypoalbuminemia, weight loss, and intractable diarrhea, while maintaining their circulating CD4 numbers. One animal died at 1.5 years of more typical simian AIDS. PMID- 8198873 TI - Production of long-lived neutralizing antibodies to HIV-1 IIIB in mice with a vaccinia recombinant virus-infected cell vaccine expressing gp160. AB - A formaldehyde-fixed cell vaccine in adjuvant (syngeneic cells infected with a vaccinia virus recombinant expressing gp160: vacc-gp160) stimulated only nonneutralizing antibody when used on its own in four strains of mice, but a similar nonfixed cell vaccine stimulated neutralizing antibodies up to a titer of 1/320 in C57BL/6 (H-2b) mice previously infected with live vacc-gp160. Synthesis of ELISA antibodies to rgp120 or rgp160 did not correspond closely to the synthesis of neutralizing antibodies and should not therefore be used to monitor the production of neutralizing antibody. The ELISA antibody response produced by boosting with the cell vaccine made with the vaccinia virus expressing gp160 under the control of a T7 promoter (vacc-gp160-PT7) was as high as that in mice given an approximately 10-fold higher dose of purified rgp160. The ELISA antibody response to the cell vaccine made with vacc-gp160-PT7 was better than that in which gp160 was expressed under the vaccinia early/late promoter (vacc-gp160 P7.5). Nearly all mice (92%; 11 of 12) primed by infection with vacc-gp160 produced comparable levels of neutralizing antibodies after a single boost with rgp160, vacc-gp160-PT7-infected cells, or vacc-gp160-P7.5-infected cells. Neutralization titers peaked at around day 22 after boost, and declined by day 29. A second boost with the same vacc-gp160-infected cells gave increased neutralizing titers in all (eight of eight) mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198875 TI - Feasibility of developing live attenuated HIV vaccines: conclusions and recommendations. World Health Organization Working Group. PMID- 8198876 TI - Lewis phenotypes, insulin resistance, and risk of ischaemic heart disease. PMID- 8198877 TI - Who needs ventricular stimulation studies? PMID- 8198878 TI - Will serum enzymes and other proteins find a clinical application in the early diagnosis of myocardial infarction? PMID- 8198879 TI - Comparison of the value of novel rapid measurement of myoglobin, creatine kinase, and creatine kinase-MB with the electrocardiogram for the diagnosis of acute myocardial infarction. AB - OBJECTIVE: To determine whether serum myoglobin, creatine kinase, and creatine kinase-MB measured at admission by rapid, compact, and easy to use automated quantitative analysers (results within 10 min) helped the early identification of acute myocardial infarction. The results were compared with the data obtained from the electrocardiograms recorded at admission. DESIGN: A prospective study. SETTING: Coronary care unit. PATIENTS: 94 consecutive patients with suspected myocardial infarction. Myocardial infarction was subsequently confirmed in 44 patients and excluded in 50. METHODS: All admission serum myoglobin, creatine kinase, and creatine kinase-MB were measured by clinical staff using analysers in the coronary care unit. An admission electrocardiogram was obtained from all patients. RESULTS: The sensitivity, specificity, and predictive accuracy for diagnosing myocardial infarction were: electrocardiogram 68%, 100%, and 85%; myoglobin 57%, 100%, and 80%; creatine kinase (threshold of 190 U/l) 34%, 98%, and 68%; creatine kinase-MB (threshold of 25 U/l) 43%, 100%, and 73%. When the electrocardiographic and myoglobin data were combined the sensitivity improved to 91%, diagnostic accuracy to 96%, with specificity of 100%. The results for the electrocardiogram and creatine kinase-MB were 80%, 90%, 100% respectively and those for the electrocardiogram with creatine kinase were 80%, 89%, 98% respectively. CONCLUSIONS: Admission myoglobin, creatine kinase, and creatine kinase-MB measurements were not as useful as the electrocardiogram for the diagnosis of acute myocardial infarction. Combining the electrocardiogram and myoglobin data substantially improved the sensitivity and predictive accuracy for the diagnosis of acute myocardial infarction. PMID- 8198880 TI - Serum Lp(a) lipoprotein concentration and outcome of thrombolytic treatment for myocardial infarction. AB - BACKGROUND: Lp(a) lipoprotein has structural homology with plasminogen and has been shown to inhibit plasminogen activation in vitro. OBJECTIVE: To determine whether the serum concentration of Lp(a) lipoprotein present when streptokinase was given in acute myocardial infarction influenced the outcome as judged by electrocardiographic methods. PATIENTS AND DESIGN: Serum Lp(a) lipoprotein concentration was measured in 135 consecutive patients admitted with a diagnosis of acute myocardial infarction who received streptokinase treatment. Recovery from myocardial injury was assessed by the reduction in the sum of ST segment elevation measured from the J point (STJ) in the electrocardiogram immediately before streptokinase was given compared with that three hours later. RESULTS: The serum Lp(a) lipoprotein concentrations were measured within 12 hours of the onset of symptoms of myocardial infarction and were higher than in healthy reference populations. Recovery from myocardial infarction could be assessed from the STJ in 116 patients (86% of the series). Those in whom it could not had bundle branch block, left ventricular hypertrophy, did not survive three hours, or had started intravenous nitrate treatment or some other clinical procedure before or at the time the second electrocardiogram was to be recorded. Patients with reductions in STJ after streptokinase that were > 4 mm (the median decrease) had mean (range) serum Lp(a) lipoprotein concentrations of 41.0 (0.8-220) mg/dl and those with a smaller reduction in STJ had concentrations of 29.1 (1.7-151) mg/dl. The difference was not statistically significant. CONCLUSION: In this study Lp(a) lipoprotein concentration did not significantly influence the outcome of thrombolytic treatment with streptokinase. PMID- 8198881 TI - Heart rate variability and its relation to ventricular arrhythmias in congestive heart failure. AB - BACKGROUND: It has been shown that heart rate variability is decreased in patients with congestive heart failure and that depressed heart rate variability is associated with a propensity to ventricular arrhythmias. Little is known, however, about heart rate variability in patients with both congestive heart failure and ventricular arrhythmias. METHODS: Spectral heart rate variability was analysed from 24 hour ambulatory electrocardiograms in 15 controls, 15 patients with non-sustained ventricular tachycardia associated with clinically normal hearts (NHVT group), and 40 patients with congestive heart failure (CHF group) secondary to either ischaemic heart disease (n = 15) or idiopathic dilated cardiomyopathy (n = 25). Of the 40 patients with congestive heart failure 15 had no appreciable ventricular arrhythmias (ventricular extrasystoles < 10 beats/h and no salvos) and formed the CHF-VA- group. Another 15 patients with congestive heart failure and non-sustained ventricular tachycardia formed the CHF-NSVT group. RESULTS: Heart rate variability was significantly lower in the CHF group than in controls (mean (SD) total frequency 23 (12) v 43 (13) ms; low frequency 12 (8) v 28 (9) ms; high frequency 8 (5) v 14 (7) ms; p < 0.001). The differences in heart rate variability between controls and the NHVT group, between ischaemic heart disease and dilated cardiomyopathy, and between the CHF-VA- and CHF-NSVT groups were not significant. In the CHF group heart rate variability was significantly related to left ventricular ejection fraction but not associated with ventricular arrhythmias. The frequency of ventricular extrasystoles was significantly related to the high frequency component of heart rate variability (r = 0.54, p < 0.05) in the NHVT group. Stepwise multiple regression analysis showed that in the CHF group, heart rate variability was predominantly related to left ventricular ejection fraction (p < 0.05). There was no significant difference in heart rate variability between survivors (n = 34) and those who died suddenly (n = 6) at one year of follow up in the CHF group. CONCLUSION: In patients with congestive heart failure, heart rate variability is significantly decreased. The depressed heart rate variability is principally related to the degree of left ventricular impairment and is independent of aetiology and the presence of ventricular arrhythmias. The data suggest that analysis of heart rate variability does not help the identification of patients with congestive heart failure at increased risk of sudden death. PMID- 8198882 TI - Influence of the autonomic nervous system on circadian patterns of myocardial ischaemia: comparison of stable angina with the early postinfarction period. AB - OBJECTIVE: To compare the circadian rhythm of myocardial ischaemia in patients with stable angina with that in patients in the early postinfarction period with particular emphasis on the role of the autonomic nervous system. PATIENTS: 44 patients with stable angina and ischaemia on treadmill testing (group A) were compared with 131 patients in the early postinfarction period (group B). All had 48 hour ambulatory Holter monitoring. SETTING: Coronary care unit and cardiology department of a district general hospital. DESIGN: Prospective, between group, comparative study. RESULTS: 337 ischaemic episodes occurred in 35 patients in group A and 370 ischaemic episodes occurred in 65 patients in group B. 34% of patients in group A had only silent episodes of ischaemia compared with 97% in group B (p < 0.0001). In group A ischaemic episodes showed a circadian rhythm that peaked during the daytime hours (p < 0.0001), but this was not seen in group B. Both the high (0.15-0.40 Hz) and low (0.04-0.15 Hz) frequency spectral components of heart rate variability showed a clear circadian rhythm (p < 0.0001); peak values occurred during the sleeping hours, although this pattern was less pronounced in group B. The ratio of low to high frequency variability (a measure of sympathovagal balance) showed a peak in daytime hours in group A (p < 0.002), but this was not seen in group B. CONCLUSION: In stable angina, myocardial ischaemia peaks during the day and is associated with a similar circadian rhythm of sympathovagal balance. In the early postinfarction period both the ischaemic and sympathovagal rhythms are severely diminished or lost altogether. Circadian changes in sympathovagal tone may explain, at least in part, the circadian rhythm of ambulatory myocardial ischaemia in patients with stable angina. PMID- 8198883 TI - Exercise testing without interruption of medication for refining the selection of mildly symptomatic patients for prognostic coronary angiography. AB - OBJECTIVE: To examine how exercise testing on background medical treatment affects the ability of the test to predict prognostically important patterns of coronary anatomy in patients with a high clinical probability of coronary artery disease but who are well controlled on medication. DESIGN: Prospective study. SETTING: Regional cardiothoracic centre and referring district general hospital. PATIENTS: 84 patients with a history of typical angina or definite myocardial infarction and mild symptoms who had been placed on the waiting list for prognostic angiography. INTERVENTION: Maximal exercise electrocardiography and radionuclide ventriculography performed off and on medication, followed by angiography within three months. MAIN OUTCOME MEASURE: Prognostically important coronary artery disease for which early surgery might be recommended purely on prognostic grounds, irrespective of symptoms. RESULTS: Coronary artery disease was present in 71/84 (85%) patients; in 28/84 (33%) patients this was prognostically important. When the result was strongly positive, the predictive accuracy for prognostically important disease was 0.46 off and 0.62 on medication for the exercise electrocardiogram and 0.71 off and 0.82 on medication for exercise radionuclide ventriculography. The likelihood ratio was 1.00 off and 1.36 on medication for exercise electrocardiography and 2.54 off and 10.5 on medication for exercise radionuclide ventriculography. In stepwise logistic regression, the test identified as the strongest predictor of prognostically important disease was exercise radionuclide ventriculography on medication for which the improvement chi 2 was 28 (p < 0.0001). With the regression model, the probability of important disease is 92% if exercise radionuclide ventriculography on medication is at least strongly positive, compared with 16% if the result is normal or just positive. CONCLUSION: In patients likely to have coronary disease, exercise testing should be performed without interruption of medication to optimise its ability to identify those with prognostically important disease, and to help to avoid unnecessary or premature angiography in those who are well controlled on medical treatment. PMID- 8198884 TI - Exercise electrocardiography and aortic Doppler velocimetry in asymptomatic identical twins discordant for type 1 (insulin dependent) diabetes. AB - OBJECTIVE: To determine the influence of insulin dependent diabetes on the prevalence of myocardial ischaemia and on global left ventricular systolic performance. DESIGN: Stress treadmill electrocardiograms and simultaneous Doppler measurement of aortic maximum acceleration were obtained during exercise on symptom free subjects. The electrocardiograms were scored blindly according to the Minnesota code. PARTICIPANTS: 39 identical twin pairs (22 male) discordant for insulin dependent diabetes and 39 non-diabetic controls of similar age and sex were examined. The twins and controls had a mean age of 37 (range 25-69) with a mean (SD) duration of diabetes in the diabetic twin of 17 (7) years. Those selected were normotensive and had no renal impairment. RESULTS: Systolic blood pressure was significantly higher in the diabetic twins than in their non diabetic cotwins both at rest (p < 0.05) and at peak exercise (p < 0.01). Electrocardiographic evidence of ischaemia was not correlated within twin pairs and was found in similar numbers of diabetic twins, their non-diabetic cotwins, and control subjects. Abnormal electrocardiograms were found in a similar number of diabetic twins (23%), non-diabetic cotwins (18%), and controls (15%). There was a significant correlation in Doppler measurements of global left ventricular systolic function within the identical twins; no significant difference was found for these Doppler measurements in the diabetic twins, non-diabetic cotwins, or controls. CONCLUSION: Exercise characteristics and cardiac function seem to be subject to shared genetic or shared environmental influences or both, whereas electrocardiographic features of ischaemia seem to be environmentally determined. In a selected cohort of diabetic identical twins without evidence of nephropathy there was no evidence that diabetes influenced the prevalence of myocardial ischaemia or global left ventricular systolic function. PMID- 8198885 TI - Hepatic portal venous flow in patients undergoing tricuspid valve surgery. AB - OBJECTIVE: To determine the changes of flow in the hepatic artery and portal vein of patients undergoing tricuspid valve repair together with mitral valve replacement. DESIGN: Non-randomised parallel group study. SETTING: Tertiary referral centre. PATIENTS: 18 patients with mitral valve disease with or without tricuspid regurgitation (age range 46-73; six men) and six patients with coronary artery disease and normal left ventricular function (women age range 39-78; four men). INTERVENTIONS: Mitral valve replacement with or without modified De Vega repair of the tricuspid valve or coronary artery bypass surgery. MAIN OUTCOME MEASURES: Flow in the hepatic artery and portal vein as measured by duplex Doppler flowmetry before and two to four weeks after operation. RESULTS: Preoperative hepatic artery flow was less in patients with mitral valve disease than in patients with coronary artery disease (162.7(13.1) ml.min-1 v 242.5(6.6) ml.min-1, p < 0.05). Portal vein perfusion was significantly reduced only in patients with associated tricuspid regurgitation compared with (844(83) ml.min-1 v 1422(64) ml.min-1 p < 0.05). Hepatic perfusion was unaltered after operation in patients undergoing coronary artery bypass surgery (p > 0.05). Flow in the hepatic artery and portal vein was improved only in patients undergoing mitral valve replacement with associated tricuspid valve repair (p < 0.05). CONCLUSION: Abnormalities of hepatic perfusion can be measured non-invasively in all patients with mitral valve disease but especially in those with associated tricuspid regurgitation needing valve repair. These abnormalities improved two to four weeks after mitral valve surgery and tricuspid valve repair, suggesting that measurement of portal flow might be a useful means of assessing the severity of tricuspid regurgitation. PMID- 8198887 TI - Successful treatment by balloon venoplasty and stent insertion of obstruction of the superior vena cava by an endocardial pacemaker lead. AB - A 63 year old man with symptomatic obstruction of the superior vena cava associated with an indwelling pacemaker was successfully treated with balloon venoplasty and stent insertion. He was symptom free with normal pacemaker function nine months later. PMID- 8198886 TI - Mitral valve hypoplasia in children with isolated coarctation of the aorta. AB - OBJECTIVE: To test the hypothesis that isolated coarctation of the aorta is associated with relative hypoplasia of the mitral valve, even when the valve is morphologically normal. DESIGN: Cross sectional and Doppler echocardiography were used in a prospective, paired, case control study to compare mitral valve dimensions and diastolic transmitral flow characteristics as indices of left heart development. 40 children with isolated coarctation and 40 size matched controls were examined. Within the coarctation group 14 children with apical diastolic murmurs were compared with 14 size matched patients without murmurs. SETTING: A supraregional tertiary referral centre for paediatric cardiology. OUTCOME MEASURES: Mitral valve diameters, measured from the parasternal long axis, short axis, and apical four chamber views; mitral valve cross sectional area measured from the parasternal short axis view; peak early (E) and peak atrial (A) phase diastolic transmitral flow velocities measured by pulsed wave Doppler from the apical four chamber view; derived E/A ratio and pressure half time of decay from peak E. RESULTS: Mitral valve dimensions were significantly smaller in children with coarctation than in controls for long axis diameter (median 1.74 v 1.90cm, p = 0.0001), short axis diameter (2.21 v 2.28 cm, p = 0.027), and cross sectional area (2.37 v 3.15 cm2, p = 0.001). Peak E and A velocities were significantly higher in patients than in controls (0.9 v 0.82 ms 1, p = 0.013 and 0.61 v 0.51 ms-1, p = 0.007). The only difference between children with coarctation plus murmurs and those without murmurs was a marginally longer pressure half time. CONCLUSIONS: Smaller mitral valve dimensions and increased diastolic transmitral flow velocities in children with isolated coarctation compared with normal children suggests that coarctation may be part of a generalised hypoplasia of left heart structures. PMID- 8198888 TI - Abnormal ventricular repolarisation in association with myocardial bridging. AB - Myocardial bridging causing systolic compression of epicardial coronary arteries may be an incidental finding at coronary arteriography. Bridging rarely causes myocardial ischaemia. A young man presented with chest pain and striking abnormalities of ventricular repolarisation that initially were treated as myocardial infarction. At cardiac catheterisation the coronary arteries were normal apart from the presence of a myocardial bridge affecting a major diagonal branch of the left anterior descending artery. Echocardiography was normal with no features of hypertrophic cardiomyopathy. PMID- 8198889 TI - Amoebiasis: a rare cause of cardiac tamponade. AB - Cardiac tamponade secondary to perforation of a hepatic amoebic abscess developed six years after the patient had visited an area where Entamoeba histolytica is endemic. He was treated with metronidazole and imipenem, emergency percutaneous catheter drainage, and open surgical drainage. PMID- 8198890 TI - Transcatheter coil embolisation of a pulmonary arteriovenous malformation in a neonate. AB - Pulmonary arteriovenous malformations (PAVM) are a rare cause of cyanosis in neonates. A large PAVM in a neonate was successfully occluded by transcatheter embolisation. At six months follow up the PAVM was undetectable and no new lesions were found. Transcatheter embolisation should be considered as the primary treatment for a PAVM in a child of any age. PMID- 8198891 TI - Temporary stent as a bail-out device during percutaneous transluminal coronary angioplasty: preliminary clinical experience. AB - OBJECTIVE: To evaluate the safety and efficacy of a prototype temporary stent (RX Flow Support Catheter, Advanced Cardiovascular Systems) in maintaining coronary perfusion and improving vessel patency in the event of acutely compromised flow complicating percutaneous transluminal coronary angioplasty. DESIGN: Prospective clinical study as part of a multicentre trial. SETTING: Regional cardiac centre catheterisation laboratory. PATIENTS: Eight patients undergoing routine percutaneous transluminal balloon coronary angioplasty in whom coronary artery dissection resulted in impaired coronary artery flow with angina or electrocardiographic ST segment shift, needing bail-out treatment at the time of the procedure. RESULTS: The RX Flow Support Catheter was successfully used and improved coronary flow in all cases, with a reduction in luminal stenosis and resolution of symptoms. The temporary stent was expanded for an average of 85 (range 30-209) minutes. In six patients it was used as a bridge to further treatment (permanent stent in four and coronary artery surgery in two) and two patients did not need further treatment. CONCLUSION: The temporary stent was safe and effective in the acute management of coronary dissection. The main advantages are its ease and speed of use, and successful restoration of coronary flow both to the distal artery and to affected side branches pending definitive treatment. PMID- 8198892 TI - A randomised comparison of the Omniflex and Magnarail systems in recanalisation of coronary occlusions. AB - OBJECTIVE: The reported success rates for angioplasty of occluded coronary arteries fall some way short of the success rates for angioplasty of sub occlusive stenoses. Two angioplasty systems used in this setting were compared. DESIGN: A prospective randomised open study comparing the Magnarail system (Schneider) and the Omniflex system (Medtronic). SETTING: A regional cardiothoracic centre performing over 300 angioplasty procedures a year. PATIENTS AND METHODS: 50 consecutive patients with occluded (thrombolysis in myocardial infarction study (TIMI) grade 0 or 1) arteries thought to be suitable for recanalisation were assigned to undergo angioplasty with either the Magnarail or Omniflex as the primary system. Twenty minutes of fluoroscopic screening was allowed with the primary randomised system before it was considered a failure. The other non-randomised system could then be used at the operators' discretion, and a further 20 minutes' screening was permitted. MAIN OUTCOME MEASURES: A patent coronary artery with a residual stenosis of < 50% with prompt distal opacification (TIMI grade 3 flow) and a reduction in collateral supply to the index artery. RESULTS: The overall success rate in recanalising occluded vessels was 72%-64% for the Magnarail system used as the primary system and 51.7% for the Omniflex (NS). The Magnarail was more successful in angioplasties of the right coronary artery (11/14 v 3/10, p = 0.02) and in mid and distal sites of occlusion (11/17 v 4/14, p < 0.05). There was a trend in favour of the Omniflex in the left anterior descending coronary artery. CONCLUSION: Both systems would seem to be suitable for angioplasty of occluded coronary arteries. The improved steerability of the Magnarail may be advantageous in distal occlusions and lesions in tortuous arteries. The relatively stiffer Omniflex may be superior for proximal occlusions. The study group was too small to confirm this unequivocally. PMID- 8198893 TI - Coronary artery bypass surgery: current practice in the United Kingdom. AB - OBJECTIVE: To assess current clinical practice in coronary artery bypass surgery and compare it with a previous survey conducted five years ago. SETTING: United Kingdom. DESIGN: Postal questionnaires were sent in March 1993 to 120 consultant cardiac surgeons currently performing coronary artery bypass surgery. 104 (87%) were returned by May 1993. RESULTS: The 104 surgeons who returned the questionnaire performed an estimated total of 25,234 coronary artery bypass operations in 1992 with an average case load per surgeon similar to that in 1987 (243 v 214, NS). The internal mammary artery was regarded as the conduit of choice by 101 surgeons (97%) and was used in 93% of bypass grafts to the left anterior descending coronary artery compared with 73% in 1987 (p < 0.001) but only in 7% of grafts to the circumflex and right coronary systems. There was also a significant increase in the number of surgeons using both internal mammary arteries (88% v 59%, p < 0.01) but only a small increase in those using the internal mammary artery as a sequential graft (55% v 44%, NS). The age of the patient remains one of the main contraindications to the use of the internal mammary artery (40%), together with insufficient mammary flow (42%), endarterectomy (22%), and unstable angina (17%). The right gastroepiploic and inferior epigastric arteries were used only occasionally (3%) when the internal mammary artery or the saphenous vein were not available. Most surgeons (96%) still advocate the use of aspirin to enhance graft patency, with 87% of surgeons continuing treatment indefinitely, compared with 50% in the previous survey (p < 0.001). As for methods of myocardial protection, 72% of surgeons used cardioplegic arrest whereas 28% preferred intermittent aortic cross clamping and fibrillation. CONCLUSIONS: It is the consensus among British cardiac surgeons that the internal mammary artery is the graft conduit of choice. Its use has been significantly extended over the past five years (1987 to 1992) suggesting a quick response to advancing scientific knowledge. The use of alternative arterial conduits is still limited, perhaps as a reflection of the relative lack of information on their long-term performance. The recently advocated technique of retrograde cardioplegia and continuous warm cardioplegia is not yet popular. PMID- 8198894 TI - Errors in manual measurement of QT intervals. AB - OBJECTIVE: To quantify the errors associated with manual measurement of QT intervals and to determine the source of the errors. DESIGN: A randomised study of QT measurement by four cardiologists of electrocardiograms plotted on paper in presentations with different noise levels, paper speeds, amplifier gains, and with and without a second QRST complex to indicate the RR interval. SUBJECTS: Four electrocardiograph leads (I, aVR, V1, V5) recorded in eight healthy people relaxing in a semirecumbent position. MAIN OUTCOME MEASURES: Manual measurement of QT interval in 512 electrocardiograms (eight subjects x four leads x eight presentations x two repeats) by each of four cardiologists. RESULTS: QT intervals measured were significantly longer with greater amplifier gain: by 8 ms for a doubling of gain (p < 0.005), equivalent to a doubling of T wave height. QT intervals measured were significantly longer at slower paper speeds: by 11 ms when paper speed was reduced from 100 to 50 mm/s (p < 0.001) and by 16 ms when speed was further reduced from 50 to 25 mm/s (p < 0.001). Neither the presence of noise nor the presence of a second QRST complex altered the mean QT measurements. There were consistent differences in the measurements between cardiologists, amounting to a maximum mean difference of 20 ms. CONCLUSIONS: Manual measurement of QT interval is significantly affected by the paper speed used to plot the electrocardiogram and by electrocardiogram gain, and hence also T wave amplitude. Manual QT measurement also differed consistently with different cardiologists. PMID- 8198895 TI - Assessment of functional capacity in chronic heart failure: time-limited exercise on a self-powered treadmill. AB - OBJECTIVES: To assess the efficacy of a 9-minute walking test on a self-powered treadmill in a group of patients with various degrees of heart failure, to investigate the reproducibility of the technique, and to establish the safety of the technique. PATIENTS AND METHODS: 24 controls and 37 patients with various grades of heart failure were studied. Peak oxygen consumption was measured in patients and controls. The distance walked in 9 minutes on a self-powered treadmill was measured in all groups and the test was repeated to assess reproducibility. RESULTS: The distance walked in 9 minutes correlated with peak oxygen consumption in patients, controls, and both groups combined. There was a significant difference in the distance walked by controls and patients and in the distance walked by patients with severe rather than with mild or moderate heart failure. There was no significant difference between the results of successive 9 minute walking tests in any group. No serious adverse reaction was seen in any patient during or after the test. CONCLUSION: The 9-minute walking test on a self powered treadmill is a sensitive, reproducible, safe, and inexpensive method of assessing functional capacity in patients with all grades of heart failure. PMID- 8198896 TI - Impact of internal audit on pacemaker prescription and the immediate costs of pacing in the northern region: towards implementation of the recommendations of the British Pacing and Electrophysiology Group. AB - BACKGROUND: In September 1990 a working party of the British Pacing and Electrophysiology Group recommended the routine use of physiological pacing systems in patients with bradycardia. An audit of the impact of these recommendations on pacemaker prescription in the Freeman Hospital between March 1990 and August 1991 has previously been reported. This paper considers the effect of that internal audit on subsequent pacemaker prescription from September 1991 to February 1993. PATIENTS AND METHODS: The records of 1228 patients who underwent first pacemaker implantation at the Freeman Hospital between March 1990 and February 1993 were audited retrospectively. The patient's age, indication for pacing, pacing mode, and cost of the generator and leads were recorded. The indications for pacing were sinus node dysfunction (24.9%) (including patients with coexistent sinus node dysfunction and atrioventricular block), atrioventricular block (57.2%), atrioventricular block and atrial fibrillation (12.2%), and carotid sinus syndrome (5.7%). There was an increase in carotid sinus syndrome (2.7% to 8.1%) between the two study periods but no other differences in the distribution of case mix or characteristics of patients. The cost of the working party's recommended optimal pacing mode was calculated from multiplication of the mean cost of the recommended unit over the second half of the study period by the number of patients who would have received that unit. RESULTS: Between March 1990 and August 1991 atrial pacing for sinus node dysfunction (AAI, AAIR, DDD, or DDDR) increased by 138% (from 25.0% to 59.6%), mainly because of increased use of AAI mode. Physiological pacing for atrioventricular block (DDD or VVIR) increased by 41% (from 17.0% to 24.0%), and VVIR pacing for atrioventricular block with atrial fibrillation increased by 111% (from 10.5% to 22.2%). After the internal audit (that is, between September 1991 and February 1993), physiological pacing for atrioventricular block increased by a further 126% (from 24.0% to 54.2%). Sixty three per cent of this increase was in the first six months after the internal audit. Pacemaker prescriptions in sinus node dysfunction and atrioventricular block with atrial fibrillation were unchanged (59.6% physiological pacing for sinus node dysfunction and 22.2% v 27.3% VVIR pacing for atrioventricular block with atrial fibrillation). These changes in practice were accompanied by an increase in the age of patients receiving physiological units. Costs of pacemaker hardware for the final six months of the audit (excluding carotid sinus syndrome) increased by 38% over the costs that would have accrued had pacing policy remained the same as for the initial six month period before the circulation of the recommendations of the working party. Adoption of the guidelines of the working party in full would lead to a further 66% increase in the costs of hardware. CONCLUSIONS: The principal effect of the recommendations of the working party alone was increased use of AAI pacing for sinus node dysfunction, with little change in the costs of hardware. The internal audit was followed by an increase in physiological pacing for atrioventricular block, and this has had important financial consequences. Internal audit was followed by closer adherence to the recommendations of the working party. PMID- 8198897 TI - Volatile agents and the ventilatory response to hypoxia. PMID- 8198898 TI - Sleep neurobiology: relevance for mechanistic studies of anaesthesia. PMID- 8198899 TI - Effect of low-dose enflurane on the ventilatory response to hypoxia in humans. AB - To investigate the effects of enflurane on the control of breathing we have studied the ventilatory responses to isocapnic hypoxia in 12 adults with and without sedation with enflurane. Design 1 consisted of three steps into hypoxia (PE' O2 = 6.7 kPa), each lasting 3 min, separated by periods of euoxia lasting 5 min (PE' O2 = 13.3 kPa). Design 1 was repeated four times in each subject on the same day in random order: with carrier gas (control) and with 0.04 MAC, 0.07 MAC and 0.13 MAC of end-tidal enflurane concentrations. Design 2 consisted of 20-min exposures to hypoxia with and without 0.07 MAC of enflurane. Each exposure was preceded and followed by 5 min of euoxia. End-tidal PCO2 was held constant at 0.13-0.27 kPa greater than the resting level throughout both designs. Mean (SEM) ventilatory responses to hypoxia for design 1 were: 8.2 (1.3) litre min-1 (control), 6.6 (1.4) litre min-1 (0.04 MAC), 5.7 (1.1) litre min-1 (0.07 MAC) and 3.7 (0.5) litre min-1 (0.13 MAC) (P < 0.001). For design 2, enflurane produced a 15% reduction in resting ventilation (P < 0.01), a 40% decrease in the acute ventilatory response to hypoxia (P < 0.01) and a 32% reduction in ventilatory decline (ns) which occurred during sustained hypoxia. PMID- 8198900 TI - Modification of the iso-shunt lines for low inspired oxygen concentrations. AB - Arterial PO2 (PaO2) has been related to inspired oxygen concentration (FIO2 range 0.21-0.60) in 20 patients, breathing spontaneously, while recovering from a range of conditions treated in an intensive therapy unit. There was a highly significant linear trend (P < 0.001) for the mean venous admixture ("virtual shunt"), calculated from the iso-shunt diagram (model A), to increase from 0.11 to 0.19 as FIO2 decreased from 0.60 to 0.21. As this appeared to be caused by relative ventilation/perfusion (V/Q) mismatch, we prepared a second model (model B) with a variable two-compartment relative V/Q mismatch in addition to a shunt. Regression of the degree of mismatch on the shunt gave good agreement between predicted and observed PaO2 values (mean bias -0.17 kPa, pooled within patient SD 1.22). Model B is now proposed to extend the applicability of the iso-shunt diagram for FIO2 values less than 0.35. Published postoperative PaO2 data from other workers showed good agreement with our final model (mean bias 0.10 kPa, pooled SD 0.41). The new diagram may therefore have wide applicability in the field of anaesthesia and intensive care. PMID- 8198901 TI - Clinical validation of a radionuclide detector to measure ejection fraction in critically ill patients. AB - The use of a new non-imaging nuclear probe (Cardioscint) capable of continuous online monitoring of left ventricular function is described in critically ill patients undergoing mechanical ventilation. Ejection fraction, measured by the Cardioscint, was compared with that measured by echocardiography. The mean difference was -1.1% (95% confidence interval -2.9 to +0.6%). Mean difference +/- 2 SD was +10.6 to -12.8% (95% confidence intervals +7.5 to 13.6% and -15.8 to 9.0%, respectively). Examples of fluid loading and inotropic support showed comparable changes in stroke counts measured by the Cardioscint and stroke index measured by thermodilution. The Cardioscint is a practical bedside method for continuous or repeated measurement of ejection fraction and for assessing the response to therapeutic interventions in critically ill patients. PMID- 8198902 TI - Comparison of i.v. and intra-tracheal administration of adrenaline. AB - Adrenaline is the single most important therapeutic agent used in advanced cardiac life support (ACLS). Ideally it should be given into a large central vein but the European Resuscitation Council, the American Heart Association and the Resuscitation Council (U.K.) advise that adrenaline may be given into the trachea if i.v. access is not available. We have studied the effects of intra-tracheal and i.v. adrenaline in 16 patients undergoing mechanical ventilation. Log dose response curves were constructed for systolic arterial pressure and heart rate responses. Intra-tracheal doses of adrenaline up to 10 micrograms kg-1, approximately one-third of that recommended for resuscitation, had no effect on arterial pressure or heart rate, whereas adrenaline 0.1 microgram kg-1 i.v. produced a mean increase in systolic pressure of 24 mm Hg. The intra-tracheal doses recommended for resuscitation (2-3 mg) are likely to be ineffective and consideration should be given to abandoning the tracheal route for adrenaline in ACLS. PMID- 8198903 TI - Comparison of patient-controlled analgesia in children by i.v. and s.c. routes of administration. AB - Sixty children undergoing appendicectomy were allocated randomly to receive one of two PCA regimens with morphine. Group IV received standard i.v. PCA with a bolus dose of morphine 20 micrograms kg-1 and a background infusion of 4 micrograms kg-1 h-1 while group SC received PCA by the s.c. route with a bolus dose of morphine 20 micrograms kg-1 and a background infusion of 5 micrograms kg 1 h-1. In both groups there was a lockout interval of 5 min. Group SC self administered significantly less morphine (P < 0.05) and had a significantly (P < 0.01) greater percentage of valid demands for analgesia than group IV. There were no differences in pain scores between the groups at rest or during movement. Group IV suffered significantly (P < 0.01) more hypoxic episodes than group SC. There were no differences between groups in the incidence of postoperative nausea and vomiting or oversedation. S.c. PCA appears to be as effective and safe as i.v. PCA. By giving patients feedback on the occurrence of valid demands for analgesia, s.c. PCA may produce more appropriate and effective use of PCA. PMID- 8198904 TI - Addition of oral clonidine to postoperative patient-controlled analgesia with i.v. morphine. AB - Using a randomized, double-blind, placebo-controlled design, we have investigated, in 40 patients undergoing major abdominal surgery, the effect of oral clonidine 300 micrograms, 1 h before and 12 h after surgery on postoperative morphine requirements (evaluated by PCA). During the 24 h of the study, pain scores measured every 6 h did not differ significantly. Morphine requirements tended to be reduced in the clonidine group but the difference was not significant. There were no significant differences also in mean arterial pressure, ventilatory frequency and the incidence of pruritus and nausea. Heart rate was significantly lower until 18 h after surgery and sedation was significantly more pronounced in patients receiving clonidine. We cannot recommend routine oral administration of clonidine before surgery to improve postoperative analgesia. PMID- 8198905 TI - Comparison of preoperative with postoperative lignocaine infiltration on postoperative analgesic requirements. AB - Ninety patients undergoing appendicectomy were allocated randomly to receive 1.5% lignocaine 15 ml with adrenaline infiltrated into the proposed wound line 3 min before incision, lignocaine 15 ml with adrenaline infiltrated into the wound on closure or no wound infiltration. After operation, all patients received pethidine by patient-controlled analgesia. Pain scores were assessed while supine and sitting on day 1 and 2 and the cumulative pethidine dose administered was recorded at 12, 24, 36 and 48 h after operation. There were no significant differences in the cumulative dose of pethidine required or pain scores between the three groups at any time point after operation. We conclude that pre incisional infiltration with 1.5% lignocaine had no advantage compared with infiltration at wound closure or no wound infiltration in reducing postoperative analgesic requirements or pain scores after appendicectomy. PMID- 8198906 TI - Double-blind comparison of ondansetron, droperidol and saline in the prevention of postoperative nausea and vomiting. AB - We have compared the efficacy of ondansetron with droperidol and saline in the prevention of postoperative nausea and vomiting (PONV) in 120 ASA I and II patients undergoing hip and knee replacements and femoral resections. They received a standardized combined extradural and general anaesthetic and at the end of surgery were allocated randomly to receive droperidol 1.25 mg, ondansetron 4 mg or 0.9% saline in a 25-ml bag. An extradural mixture containing 0.5% plain bupivacaine 10 ml, fentanyl 500 micrograms and saline 30 ml was infused and PONV assessed for 24 h. Both ondansetron and droperidol were superior to saline in preventing vomiting (P < 0.01) although there was no significant difference between them. The incidence of vomiting was 17% for ondansetron, 18% for droperidol and 45% for saline. There was no significant difference in the incidence of nausea between the groups. Metoclopramide, the rescue antiemetric, was demanded by 38%, 34% and 17% of patients receiving saline, droperidol and ondansetron, respectively (ondansetron vs droperidol P < 0.05). PMID- 8198907 TI - Calculation of mean skin temperature and changes in body heat content during paediatric anaesthesia. AB - Mean skin temperature and changes in body heat content were calculated in several different ways from measurements made in five children during operation. Mean skin temperatures were calculated from 162 sets of measurements using 15, 12, eight, seven and four skin sites with various formulae modified according to age. The results of other formulae were compared with age-adjusted, area-weighted 15 site mean skin temperature which was used as a reference. Changes in body heat content were calculated from Burton's equation in different ways and errors from different variables in the formula were evaluated. Mean skin temperature from 12 skin sites was within 0.5 degrees C of the 15-point reference method, and that from four sites within 1 degree C. The core temperature selected and the weighting coefficients used in calculating mean body temperature were more important sources of error in the determination of change in body heat content than was mean skin temperature. PMID- 8198908 TI - Recovery after propofol infusion anaesthesia in children: comparison with propofol, thiopentone or halothane induction followed by halothane maintenance. AB - We have compared the recovery profiles of 163 healthy Chinese children after general anaesthesia for minor surgical procedures. Patients were allocated randomly to receive one of four anaesthetic techniques: propofol infusion for induction and maintenance using a pharmacokinetic model-controlled syringe pump set initially at a target concentration of 8 micrograms ml-1 and then adjusted according to clinical requirements; propofol 2.5-3.5 mg kg-1, thiopentone 4-5 mg kg-1 or 2-3% halothane for induction of anaesthesia followed by 1-2% halothane for maintenance of anaesthesia. All patients breathed a mixture of 70% nitrous oxide in oxygen through a laryngeal mask airway and received an appropriate regional anaesthetic block. Recovery was assessed using the time to achieve full Steward score, open eyes on command, orientation and the time required to complete a simple puzzle. Recovery was slowest with the propofol infusion (mean 39.8 (SD 12.9) min when eyes opened on command). The recovery times were significantly shorter with the three other techniques (propofol bolus 21.9 (9.9) min, thiopentone 23.4 (11.3) min, halothane 20.1 (8.9) min), and the choice among these three methods had no significant influence on the recovery profile. PMID- 8198909 TI - Recovery after oral surgery with halothane, enflurane, isoflurane or propofol anaesthesia. AB - We have compared the recovery characteristics of four different techniques for maintenance of anaesthesia in 99 day-case patients admitted for oral surgery. All patients received propofol for induction of anaesthesia followed by halothane, enflurane, isoflurane or propofol infusion for maintenance of anaesthesia. Each patient was subjected to a battery of psychometric tests which included Spielberger state, trait, mood stress and mood arousal questionnaires, Maddox Wing test and five-choice serial reaction time. All tests were performed before operation and at 0.5, 1, 2, 4, 24 and 48 h after operation. Performance in the reaction time test decreased significantly in the immediate postoperative period, returning almost to preoperative values by 4 h. However, only those patients who received enflurane or propofol had returned to their performance level before surgery by 4 h, although all four groups had achieved this target by 24 h. There was a further improvement in performance at 48 h. Anxiety and stress were high before surgery and decreased rapidly in the postoperative period. The Maddox-Wing test demonstrated a significant impairment in performance in the first 1 h after surgery, which returned to normal by discharge at 4 h. There were no significant differences between the four groups in these latter tests. PMID- 8198910 TI - Effects of amrinone on left and right ventricular function in patients with impaired myocardial performance during general anaesthesia. AB - We have studied the effects of amrinone on left and right ventricular haemodynamics in patients with impaired ventricular performance caused by coronary artery disease. Anaesthesia was achieved with fentanyl, flunitrazepam and pancuronium. After reaching steady state, a bolus dose of amrinone 0.5 mg kg 1 was administered followed by an infusion of 1 mg kg-1 h-1. Right ventricular ejection fraction (RVEF) and other haemodynamic variables were evaluated at six times: before, 5, 10, 15, 20 and 30 min after bolus administration of amrinone. Amrinone led to a 23% increase in cardiac index resulting mainly from reduction in afterload. While central venous pressure and mean pulmonary artery pressure remained unchanged, RVEF increased by 28%. This effect may be interpreted as an improvement in right ventricular performance. PMID- 8198911 TI - Plasma concentration and protein binding of alfentanil during high-dose infusion for cardiac surgery. AB - We have studied plasma protein binding of alfentanil in 10 patients given a mean total dose of 949 micrograms kg-1 as the principal anaesthetic agent for coronary artery bypass grafting. The mean unbound fraction of plasma alfentanil increased from 0.09 to 0.16 after administration of heparin and to 0.26 after beginning cardiopulmonary bypass (CPB). After CPB until the end of surgery, the unbound fraction decreased to 0.12. These changes in the unbound fraction were associated with significant changes in plasma total and unbound concentrations of alfentanil also. Within the first 1 min of CPB, total alfentanil concentration had decreased by more than the unbound concentration and the decrease observed in the latter disappeared rapidly. From induction of anaesthesia until awakening of the patient, plasma protein binding of alfentanil was related significantly (P = 0.0166) to the serum concentration of orosomucoid (alpha 1-acid glyco-protein). PMID- 8198912 TI - Choline acetyltransferase activity of rat synaptosomes is sensitive to enflurane, but not halothane or isoflurane. AB - We have examined the activity of choline acetyltransferase (ChAT) in rat cortical synaptosomes in the presence of three volatile anaesthetic agents: enflurane, halothane and isoflurane. The Michaelis constant Km, for choline was reduced significantly (P = 0.012) in the presence of 6.5% enflurane (3 rat MAC) compared with control samples exposed to carrier air only, while maximum reaction velocity (Vmax) remained unaltered. The reduction in Km was also significant at enflurane concentrations of 4.4% (2 rat MAC) (P = 0.043) and 2.2% (1 rat MAC) (P = 0.043). Halothane 3% (2.5 rat MAC) and 4.5% isoflurane (3 rat MAC) had no effect on either kinetic property. If present in vivo, an enflurane-induced alteration in acetylcholine metabolism, through modified ChAT, may contribute to the convulsive properties of this anaesthetic. PMID- 8198913 TI - Influence of halothane and isoflurane on the contractile responses to potassium and prostaglandin F2 alpha in isolated human pial arteries. AB - Volatile anaesthetics may modulate cerebrovascular resistance, but their direct actions on human cerebral arteries are unknown. In the present study, we have evaluated the effects of halothane and isoflurane at different MAC (0.4, 1.0 and 2.0) on contractions induced by depolarization (potassium) or receptor stimulation (prostaglandin F2 alpha) in isolated ring segments of human pial arteries. Neither halothane nor isoflurane had significant effects on potency (unaffected EC50 value) or the maximum response (Emax) in potassium-contracted arteries, even though there was a general tendency to attenuation of Emax. Similarly, the potency of prostaglandin F2 alpha was unchanged (unaffected EC50 value). However, the Emax value for prostaglandin F2 alpha at normocapnia (mean PCO2 4.3 (SEM 0.1) kPa, pH 7.41 (0.01)) and addition of halothane (0.4, 1.0 and 2.0 MAC) was significantly attenuated to 96 (2)%, 91 (3)% and 84 (4)% at the respective MAC concentrations. Isoflurane at 2 MAC and normocapnia also reduced Emax to 94 (3)%. During hypocapnia (PCO2 2.7 (0.1) kPa, pH 7.64 (0.01)), the vasodilator effect of halothane was reduced, whereas isoflurane at 0.4 and 1.0 MAC enhanced the contraction induced by prostaglandin F2 alpha. PMID- 8198914 TI - Influence of surface morphology on in vitro bacterial adherence to central venous catheters. AB - The detailed surface topography of five polyurethane central venous catheters (CVC) (Hydrocath, Deltacath, Certofix trio, Arrow-Howes and Multicath three) was examined by scanning electron microscopy and laser profilometry. The results were correlated with the ability of Staphylococcus epidermidis to adhere to each CVC. Hydrocath CVC had the smoothest surface, as determined by profile peak values of 0.17 microns (Ra) and 0.94 microns (Rz). These CVC also had the lowest number of staphylococci adhering to the surface. In contrast, Certofix trio CVC had an irregular surface (Ra 1.29 microns and Rz 6.35 microns) which was confirmed by scanning electron microscopy. These latter CVC had significantly more bacteria colonizing their surface compared with Hydrocath and Arrow-Howes CVC (P < 0.01). The results suggest that a CVC with a smooth surface, absent of surface defects, may reduce the risk of colonization with bacteria and therefore subsequent sepsis. PMID- 8198915 TI - Reduction in postoperative vomiting after surgical correction of prominent ears. AB - There is a high incidence of postoperative nausea and vomiting after surgical correction of prominent ears. A prospective, randomized study was performed to determine if the method of dressing the ears influenced the incidence of postoperative vomiting. Avoidance of packing the external auditory meatus and concha produced a significant reduction in postoperative nausea (83% vs 30%; P < 0.005) and vomiting (63% vs 22%; P < 0.01). PMID- 8198916 TI - Haemodynamic and catecholamine changes after induction of anaesthesia with either thiopentone or propofol with suxamethonium. AB - We have compared the haemodynamic and catecholamine responses to laryngoscopy and tracheal intubation in 43 patients after induction of anaesthesia with either thiopentone 5.1 (SD 0.9) mg kg-1 or propofol 2.2 (0.1) mg kg-1, each with suxamethonium and without opioid pretreatment. Heart rate increased significantly above baseline after induction and intubation in both groups, but there were no differences between groups. Arterial pressure increased significantly at 1 min after intubation in both groups and at 2 min in the thiopentone group only. Plasma concentrations of adrenaline increased significantly compared with concentrations before induction, 1 min after intubation in both groups and at 2 min in the thiopentone group only. Plasma concentrations of adrenaline were significantly greater in the thiopentone group than in the propofol group at both 1 and 2 min after intubation. Plasma concentrations of noradrenaline showed no significant time-based within-group changes, but were significantly greater in the thiopentone group at 1 and 2 min after intubation. We conclude that doses of either thiopentone or propofol sufficient to obtund the eyelash reflex with suxamethonium 1 mg kg-1 alone do not adequately block the catecholamine and hypertensive responses to laryngoscopy and intubation in normal patients and although propofol suppressed increases in catecholamines to a greater extent than thiopentone, there were no clinical advantages. PMID- 8198917 TI - Comparison of the effects of isoflurane and propofol on hepatic glutathione-S transferase concentrations during and after prolonged anaesthesia. AB - We have studied the effects of isoflurane or propofol anaesthesia on hepatic glutathione-S-transferase (GST) concentrations in 20 patients during and after prolonged plastic and reconstructive surgery (approximately 10 h). Mean plasma concentrations of GST did not exceed the normal range in any sample from any patient. Although GST concentrations in the propofol group were smaller than those in the isoflurane group, these differences were not statistically significant. These data show that prolonged propofol or isoflurane anaesthesia has no statistically significant effect on plasma concentrations of GST during and after extended surgery. PMID- 8198918 TI - Hyperkalaemia associated with prolonged insufflation of carbon dioxide into the peritoneal cavity. AB - We measured plasma potassium concentrations in five anaesthetized pigs over a 3.5 h period during which a carbon dioxide pneumoperitoneum was maintained. During this period the abdominal pressure was kept at 1.96 kPa and normocapnia was maintained by intermittent positive pressure ventilation. The potassium concentration was found to increase with time to a mean of 5.63 (SD 0.44) mmol litre-1. Consideration should be given to monitoring plasma potassium concentration in patients undergoing prolonged laparoscopic surgery. PMID- 8198919 TI - An unusual cause of postoperative brachial plexus palsy. AB - We describe a case of postoperative brachial plexus neurapraxia after lumbar spinal surgery performed on the prone, seated, knee-chest position. The arms were extended above the patient's head. PMID- 8198920 TI - Calcium channel inhibitors and perioperative myocardial ischaemia in cardiac surgery. PMID- 8198921 TI - Morphine and droperidol combined in patient-controlled analgesia; reduction of nausea and vomiting. PMID- 8198922 TI - Outliers and extrapolation: child's age and infusion rates of mivacurium. PMID- 8198923 TI - Coughing during induction caused by morphinomimetic drugs. PMID- 8198924 TI - Comparison of the Belscope with the Macintosh laryngoscope. PMID- 8198925 TI - Detection of perioperative myocardial ischaemia. PMID- 8198926 TI - Intrathecal position of microcatheters. PMID- 8198927 TI - 'The strategy of desire' and rational prescribing. PMID- 8198928 TI - Dose of midazolam should be reduced during diltiazem and verapamil treatments. AB - 1. The effects of diltiazem and verapamil on the pharmacokinetics and pharmacodynamics of midazolam were investigated in a double-blind randomized cross-over study of three phases. 2. Nine healthy volunteers were given orally diltiazem (60 mg), verapamil (80 mg) or placebo three times daily for 2 days. On the second day they received a 15 mg oral dose of midazolam, after which plasma samples were collected and performance tests carried out for 17 h. 3. The area under the midazolam concentration-time curve was increased from 12 +/- 1 microgram ml-1 min to 45 +/- 5 micrograms ml-1 min by diltiazem (P < 0.001) and to 35 +/- 5 micrograms ml-1 min by verapamil (P < 0.001). The peak midazolam concentration was doubled (P < 0.01) and the elimination half-life of midazolam prolonged (P < 0.05) by both diltiazem and verapamil treatments. 4. These changes in the pharmacokinetics of midazolam were also associated with profound and prolonged sedative effects. 5. If the administration of midazolam cannot be avoided, the dose of midazolam should be reduced during concomitant treatment with diltiazem and verapamil. PMID- 8198929 TI - The efficacy of locally applied morphine in post-operative pain after bilateral third molar surgery. AB - 1. Recent evidence has hinted at a peripheral site of action of morphine analgesic efficacy. 2. Previous studies by the same authors have developed a model for testing local analgesic efficacy by placing drugs into tooth sockets after third molar surgery. 3. The present studies test the hypothesis of local morphine activity at two dosage concentrations, 100 ng ml-1 and 100 micrograms ml 1 after third molar surgery. 4. No significant analgesic efficacy was found at either dose when compared with placebo. PMID- 8198930 TI - Do cholesterol-lowering agents affect brain activity? A comparison of simvastatin, pravastatin, and placebo in healthy volunteers. AB - 1. The effects of simvastatin and pravastatin on measures of central nervous system activity were investigated in a double-blind, placebo-controlled, randomised crossover study. 2. Twenty-five healthy volunteers sequentially took 40 mg day-1 simvastatin, 40 mg day-1 pravastatin or placebo for 4 weeks, separated by a 4-6 week washout phase. 3. CNS measures included EEG evoked potentials, power spectral analysis, Leeds Sleep Questionnaire, Hospital Anxiety Depression (HAD) Scale, and Digit Symbol Substitution Test (DSST); biochemical measures included plasma cholesterol, liver enzymes (gamma-GT, AST, ALT) and creatine kinase. 4. Mean cholesterol concentrations with both drugs were significantly lower than with placebo, and the cholesterol-lowering effect was greater with simvastatin. There were no significant differences between treatment in EEG evoked potentials, HAD Scale, or DSST scores. On the sleep measure, subjects reported significantly greater difficulty in getting to sleep while on simvastatin than on pravastatin, but neither score differed from placebo. No significant correlations were observed between sleep ratings and either plasma cholesterol concentrations or EEG evoked potentials. 5. The study showed that, while both drugs reduced plasma cholesterol concentrations, neither exerted significant effects, compared with placebo, on EEG evoked potentials, mood, sleep, or cognitive performance after 4 weeks of chronic administration in healthy volunteers. PMID- 8198931 TI - The role of S-mephenytoin 4'-hydroxylase in imipramine metabolism by human liver microsomes: a two-enzyme kinetic analysis of N-demethylation and 2-hydroxylation. AB - 1. The metabolism of imipramine (N-demethylation and 2-hydroxylation) was studied in relation to the activity of S-mephenytoin 4'-hydroxylase in human liver microsomes. 2. Eadie-Hofstee plots for the formation of despiramine and 2 hydroxyimipramine were biphasic, suggesting that at least two enzymes are involved in both the N-demethylation and 2-hydroxylation of imipramine by human liver microsomes. 3. The respective mean (+/- s.d.) kinetic parameters for the N demethylation and 2-hydroxylation of imipramine derived from a two-enzyme kinetic analysis were: Km1 = 1.1 +/- 0.4 and 1.6 +/- 0.6 microM, Vmax1 = 0.11 +/- 0.03 and 0.15 +/- 0.07 nmol mg-1 min-1, and Vmax1/Km1 = 0.10 +/- 0.02 and 0.09 +/- 0.04 ml mg-1 min-1; Km2 = 214 +/- 84 and 257 +/- 148 microM, Vmax2 = 2.22 +/- 0.69 and 0.53 +/- 0.15 nmol mg-1 min-1, and Vmax2/Km2 = 0.011 +/- 0.001 and 0.003 +/- 0.002 ml mg-1 min-1. 4. With regard to imipramine N-demethylation and 2 hydroxylation at 2 microM (representing high-affinity reactions) and at 400 microM (representing low-affinity reactions), only N-demethylation at 2 microM showed a close correlation with the 4'-hydroxylation of S-mephenytoin (rs = 0.952, P < 0.01; n = 10 livers). 5. Concentrations up to 250 microM S-mephenytoin inhibited the N-demethylation of imipramine (2 microM), but no further inhibition was observed using concentrations from 250 to 750 microM. 6. Imipramine inhibited S-mephenytoin 4'-hydroxylation competitively with a Ki value of 12.5 microM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198932 TI - Pharmacokinetics of rac-leucovorin vs [S]-leucovorin in patients with advanced gastrointestinal cancer. AB - 1. The pharmacokinetics of [R]-leucovorin ([R]-LV), [S]-leucovorin ([S]-LV) and the circulating metabolite [S]-5-methyltetrahydrofolate ([S]-5-MTHF) were studied after administration of racemic LV and [S]-LV in 21 subjects. 2. After intravenous infusion of 600 mg m-2 rac-LV (group 1, n = 7) or 300 mg m-2 [S]-LV (group 3, n = 7), the decay of [S]-LV in plasma was biexponential with a distribution half-life of 0.8 to 1 h and an elimination half-life of 11 to 23 h. When rac-LV was administered as a 2 h i.v. infusion (400 mg m-2) following a loading dose of 200 mg m-2 (group 2, n = 7), the plasma concentrations of [R]-LV and [S]-5-MTHF decayed monoexponentially with mean (+/- s.d.) half-lives of 10 +/ 3 h and 7 +/- 2 h, respectively. 3. The AUC of [S]-5-MTHF was significantly higher after infusion of 300 mg m-2 [S]-LV than after infusion of 600 mg m-2 rac LV (83 +/- 22 micrograms ml-1 h vs 53 +/- 22 micrograms ml-1 h; P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198933 TI - Pharmacokinetics of artemether after oral administration to healthy Thai males and patients with acute, uncomplicated falciparum malaria. AB - 1. The pharmacokinetics of artemether were investigated (a) in six healthy male Thai volunteers after single 200 mg oral doses and (b) in eight male Thai patients with acute uncomplicated falciparum malaria after an initial 200 mg oral dose followed by 100 mg at 12 h then 100 mg daily for 4 days. 2. In the healthy subjects, median (range) maximum plasma concentrations of artemether of 118 (112 127) ng ml-1 were reached at 3 (1-10) h. Thereafter, drug concentrations declined monoexponentially with a median (range) t1/2.z of 3.1 (1.0-9.6) h. The median (range) AUC and MRT values were 1.10 (0.33-4.44) micrograms ml-1 h and 8.3 (3.5 20.8) h. The median Cmax value of dihydroartemisinin, an active metabolite, was 379 (162-702) mg ml-1 at 6 (2-12) h. Its median AUC value was 6.6 (0.83-38.7) micrograms ml-1 h; the apparent t1/2.z was 10.6 (4.7-19.2) h and the median MRT value was 16.0 (5.0-41.0) h. 3. In the patients, a higher Cmax value of parent drug than those observed in healthy subjects (median and range of 231 (116-411) ng ml-1), was reached at 3 (1-3) h after the first dose. Steady state was reached after the third dose (24 h) and concentrations fluctuated over the range of 36-60 ng ml-1. The respective median (range) values of AUC and t1/2.z were 5.8 (3.76 12.9) micrograms ml-1 h and 4.2 (2.5-5.3) h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198934 TI - Multicentre hospital drug utilization study on the prophylaxis of venous thromboembolism. The Venous Thromboembolism Study Group of the Spanish Society of Clinical Pharmacology. AB - 1. Thromboembolic disease (TED) is an important cause of in-hospital morbidity and mortality. Although different prophylactic approaches have been shown to be effective and cost-effective, surveys have suggested that they are underused. The aim of this study was to estimate the prevalence of use of TED prophylaxis in our hospitals. 2. All patients admitted on a specified day to the Internal Medicine and General Surgery wards of seven Spanish university hospitals were included in the study. They were identified cross-sectionally and followed up until discharge or for 15 days. Information about the following variables was collected: risk factors for venous thromboembolism, prophylactic measures used (if any), contraindications to the use of each specific drug or other prophylactic measure, and dosage schedule of the drug used, if any. 3. Nine hundred and thirty-nine patients (53% men) were studied. The most common risk factors for venous thromboembolism were: age > or = 40 years (802; 85%), major surgery (298; 32%), immobilization > or = 6 days (285; 30%), obesity (241; 26%), and cancer (202; 22%). 4. Prophylactic measures were used in 320 patients (34%). Of these, 297 (93%) received heparin, mainly as low molecular weight heparins (248, 78%); physical measures were rarely used. 5. Five hundred and eighty-three patients (62%) fulfilled criteria for moderate or high risk of venous thromboembolism; only 275 (47%) of them received any form of prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198935 TI - The acute effects of a single dopamine infusion in elderly patients with congestive cardiac failure. AB - 1. Dopamine (DA) at low doses (2.5 micrograms kg-1 min-1) produces a measurable increase in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in young healthy subjects and has a therapeutic effect in younger patients with congestive cardiac failure (CCF). In elderly healthy subjects, DA increases ERPF but does not increase GFR in all subjects. 2. To determine the potential therapeutic use of DA in elderly subjects with CCF, we studied 17 patients (5 male) aged 79.9 years (range 68 to 93 years) admitted to hospital for inpatient treatment of CCF resistant to diuretic and angiotensin converting enzyme inhibitor therapy. The effects of a single infusion DA at 2.5 micrograms kg-1 min 1 on GFR and ERPF were assessed in a double-blind, placebo controlled prospective study. 3. There were no significant differences in GFR or ERPF between control and DA. A reduction in GFR was seen in some patients. 4. DA at low dosage was not shown to benefit elderly patients with resistant CCF, and in some patients was detrimental. Higher doses or a combination with other inotropes may be necessary for a renal effect in elderly patients. PMID- 8198936 TI - Dose finding studies with imidapril--a new ACE inhibitor. AB - 1. We describe an approach involving a smaller, shorter study, leading onto a longer, larger study in which the antihypertensive effects of ascending doses of imidapril, a new ACE inhibitor, were investigated. Both studies were planned prospectively, assuming a clinically useful fall in BP to be 8 mm Hg (s.d. = 9). The studies included patients with mild to moderate essential hypertension (baseline sitting diastolic blood pressure (SDBP) 95-115 mm Hg). After a placebo run-in of 2-3 weeks patients received either placebo or imidapril 2.5, 5, 10 or 20 mg in the 2 week study (n = 91) or imidapril 5, 10, 20 or 40 mg in the 4 week study (n = 162). 2. The overall mean baseline SDBP was 103.4 mm Hg (s.d. 0.62) in the initial study and 101.5 mm Hg (s.d. 0.41) in the 4 week study. 3. Compared with placebo, imidapril 10, 20 and 40 mg significantly reduced SDBP. There was no significant difference between these doses, suggesting that 10 mg achieved maximal ACE inhibition in most patients. The 2.5 mg dose showed no significant effect. The 5 mg dose gave an intermediate effect. In both studies the overall incidence of adverse events was similar in the imidapril and placebo groups, and was not worrying. PMID- 8198937 TI - Comparative effects of angiotensin II on Doppler parameters of left and right heart systolic and diastolic blood flow. AB - 1. The purpose of the study was to investigate the effects of angiotensin II on Doppler parameters of right ventricular systolic and diastolic blood flow, and to compare these with effects on the left heart, in normal subjects. 2. Pulsed-wave Doppler measurements were made in eight normal volunteers: after a 30 min control i.v. infusion of dextrose, after 30 min stepwise infusions of angiotensin II (2, 4 and 6 ng kg-1 min-1), and finally 30 min after stopping the 6 ng kg-1 min-1 dose of angiotensin II. Aortic (Ao) and pulmonary (Po) systolic ejection parameters, as well as mitral (Mi) and tricuspid (Tc) diastolic filling parameters were measured. 3. Ao and Po maximal velocity were both significantly reduced by angiotensin II, whereas there were significant opposite effects on Ao (reduced) and Po (increased) mean acceleration. There was a dose-related fall in Po acceleration time with angiotensin II, whilst Ao acceleration time remained unchanged. 4. Mi and Tc early diastolic filling velocities were not significantly altered by angiotensin II compared with baseline, although there was a significant rebound increase in both Mi and Tc early filling after cessation of angiotensin II infusion. Mi and Tc pressure half-times were not significantly changed. 5. In conclusion, angiotensin II produced changes in Po ejection parameters consistent with a pressor response in the pulmonary vascular bed. Neither right nor left ventricular diastolic filling were directly affected by angiotensin II. The differential effects of angiotensin II on Po and Ao ejection parameters might be due to inherent differences in basal pulmonary and systemic vascular tone. PMID- 8198938 TI - Trimetazidine: a new concept in the treatment of angina. Comparison with propranolol in patients with stable angina. Trimetazidine European Multicenter Study Group. AB - 1. Trimetazidine has a direct anti-ischaemic effect on the myocardium without altering the rate x pressure product or coronary blood flow. 2. The effects of trimetazidine (20 mg three times daily) were compared with those of propranolol (40 mg three times daily) in a double-blind parallel group multicentre study in 149 men with stable angina. 3. Reproducibility of exercise performance was verified during a 3 week run-in placebo washout period. All patients had > 1 mm ST-depression on exercise test. 4. After 3 months, similar anti-anginal efficacy was observed between the trimetazidine (n = 71) and propranolol (n = 78) groups. No significant differences were observed between trimetazidine and propranolol as regards anginal attack rate per week (mean difference P-TMZ: 2; 95% CI: -4.4, 0.5) and exercise duration (mean difference P-TMZ: 0 s; 95% CI: -33, 34) or time to 1 mm ST segment depression (mean difference P-TMZ: 13 s; 95% CI: -24, 51). Heart rate and rate x pressure product at rest and at peak exercise remained unchanged in the trimetazidine group but significantly decreased with propranolol (P < 0.001 in all cases). With both drugs there was a trend to decreased ischaemic episodes in the 46% patients who experienced ambulatory ischaemia on Holter monitoring. Six patients stopped trimetazidine and 12 propranolol. Of these, five in each group were withdrawn because of deterioration in cardiovascular status. 5. The results suggest that trimetazidine and propranolol at the doses studied have similar efficacy in patients with stable angina pectoris.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198939 TI - Failure to reproduce the in vitro cardiac electrophysiological effects of naloxone in humans. AB - 1. Opioid receptor antagonists such as naloxone have shown antiarrhythmic activity in animal models of coronary artery occlusion. Studies have indicated that these effects are stereospecific but both isomers of naloxone prolong action potential duration and refractoriness in guinea-pig and rabbit isolated ventricular myocardium (Class III effect). 2. This study was performed to identify whether this Class III effect of naloxone could be reproduced in human myocardium in vivo. Twenty patients with coronary artery disease received intravenous racemic naloxone (1-40 micrograms kg-1 min-1). Surface electrocardiographic parameters were measured and refractory periods were determined during fixed rate pacing by programmed stimulation. 3. The corrected QT interval during sinus rhythm (SR-QTc) was prolonged by 5(3)% (P = 0.06) at a dose of 20 micrograms kg-1 min-1 and by 9(10)% at 40 micrograms kg-1 min-1 (P = 0.03). These small changes were lost at higher paced heart rates. No significant effects on atrial, atrioventricular nodal or ventricular refractoriness were seen. 4. Plasma naloxone concentrations well into the micromolar range were achieved with both of the higher doses of naloxone administered. Plasma beta endorphin concentrations invariably increased following naloxone infusion. There was no statistical relationship between peak plasma naloxone concentrations and the absolute or percent prolongation of SR-QTc. 5. It seems unlikely that racemic naloxone would have any clinical utility as an antiarrhythmic agent. Racemic naloxone may enhance cardiac adrenergic nerve activity and this receptor mediated effect may have prevented the demonstration of any nonreceptor mediated prolongation of cardiac refractoriness. Studies with the individual stereoisomers of naloxone would be of interest. PMID- 8198940 TI - Cefpiramide kinetics and plasma protein binding in cholestasis. AB - Cefpiramide is a new parenteral cephalosporin mainly excreted in the bile. Eight patients with cholestasis and 11 healthy subjects received a single 1 g i.v. dose. Cefpiramide concentrations in plasma and urine were measured by h.p.l.c. and plasma binding was determined by ultrafiltration. Total clearance of cefpiramide (mean +/- s.d.) was 15.5 +/- 7.1 ml min-1 in patients and 25.6 +/- 4.6 ml min-1 in healthy subjects. As a result, the terminal elimination half-life was longer in patients (12.0 +/- 2.9 h vs 5.3 +/- 0.9 h). Owing to impaired biliary elimination of cefpiramide in cholestasis, the urinary recovery of unchanged drug in patients was about five times greater than in healthy subjects (85.1 +/- 10.3% vs 16.2 +/- 3.9%). Plasma binding was significantly lower in cholestasis (fu = 0.23 +/- 0.13 vs 0.02 +/- 0.004 in healthy subjects). Accordingly, the dosage regimen of cefpiramide should be modified in patients with cholestasis. PMID- 8198941 TI - The effect of liver disease and food on plasma MEGX concentrations. AB - Plasma monoethylglycinexylidide (MEGX) concentrations were measured in 15 healthy controls (age 23-46 years) and 12 patients with biopsy proven cirrhosis (age 34 70 years) 30 min after 1 mg kg-1 intravenous lignocaine. Mean (+/- s.d.) MEGX concentrations were 57 +/- 33 ng ml-1 in the controls compared with 21 +/- 18 ng ml-1 in the cirrhotics (P < 0.05), but there was overlap in the range of concentrations. MEGX concentrations were inversely correlated with age, but not disease severity, in the cirrhotic patients (r = 0.62, P = 0.04) but not in the control subjects. In a second study 20 healthy subjects were given 1 mg kg-1 intravenous lignocaine on two occasions; either fed or fasted, and samples taken at 15, 30 and 60 min after dosage. MEGX concentrations were not significantly different at any time within either day or between fed and fasted study days. There was no correlation with age. The plasma lignocaine concentration at 15 min was significantly higher fed than fasted (2.88 +/- 2.44 and 1.82 +/- 0.96 micrograms ml-1, P = 0.01). Measurement of plasma MEGX after i.v. lignocaine is a useful test of liver function and may be performed in fed or fasted subjects. It is reproducible within an individual but is not specific for cirrhosis and appears age-related in liver disease. PMID- 8198942 TI - The pharmacokinetics of quinapril and quinaprilat in patients with congestive heart failure. AB - The pharmacokinetics of quinapril and its active metabolite quinaprilat were studied in 12 patients with congestive heart failure (CHF) after multiple oral doses of 10 mg quinapril twice daily. Six patients had an ejection fraction of < 35% and six had an ejection fraction between 35%-50%. Increases in the apparent elimination half-life and in AUC(0, 12h) values of quinaprilat were associated with smaller ejection fractions, decreased creatinine clearance, and increased patient age. Comparison with data from age-matched controls having comparable renal function suggests that creatinine clearance is the major determinant of quinaprilat clearance. CHF per se appears to have minimal effect. Dosing of quinapril in patients with CHF should be based on their renal function. PMID- 8198943 TI - The effect of physiological manoeuvres on the absorption of inhaled nedocromil sodium. AB - In a previous study we showed, in both asthmatic patients and in healthy subjects, a marked increase in plasma concentration of nedocromil immediately following an exercise challenge with associated FEV1 measurements. To identify which component of the exercise challenge is responsible, we have now studied the effect of various manoeuvres on plasma nedocromil concentration in eight healthy subjects after inhalation of 1 ml nedocromil solution (1% w/v) via a Wright nebuliser. Each patient was dosed on six occasions, separated by at least 3 days. Between 15 and 23 min after dosing one of the following manoeuvres was performed: control (no manoeuvre); steady exercise for 8 min, a series of FEV1 measurements, exercise plus FEV1 measurements, three Valsalva manoeuvres and hyperventilation for 3 min. Mean plasma drug concentrations under control conditions were similar at 15 and 23 min after dosing. However, there were significant increases in plasma drug concentration following exercise, FEV1 manoeuvres and exercise plus FEV1 manoeuvre. There were no significant changes in plasma drug concentration following Valsalva manoeuvres and hyperventilation. The results suggest that certain manoeuvres increase the absorption of nedocromil sodium, probably as a consequence of an increase in lung volume. PMID- 8198944 TI - Symptomatic, nonruptured abdominal aortic aneurysms: are emergent operations necessary? AB - To evaluate current morbidity and mortality and to define the best strategy of management, we retrospectively reviewed the clinical histories of 36 patients (24 males and 12 females) who underwent repair of symptomatic, nonruptured abdominal aortic aneurysms (AAAs) between April 1, 1987, and April 30, 1992, at the Mayo Clinic (3.2% of 1111 patients with AAA repair). Ages ranged from 54 to 94 years (mean 75 years). All patients were hemodynamically stable and presented with abdominal and/or back pain of 1 to 60 days' duration (mean 11.6 days). The diagnosis of AAA was confirmed by CT scan in 26 patients, ultrasonogram in seven, and plain abdominal films in three. Fourteen patients (38.9%) were operated on emergently within 4 hours of admission, 11 (30.5%) between 4 and 24 hours, and 11 between 24 hours and 7 days following presentation (mean 28.9 hours). Eight (22.2%) had inflammatory aneurysm. AAAs were repaired with a straight graft in 17 patients and a bifurcated graft in 19. Complications occurred in 24 patients (66.7%). Mortality was 11.1% (4/36). The association between emergency repair (< 4 hours) and 60-day mortality was significant (p < 0.05). There were no deaths among those patients whose operation was delayed. Comparison to a matched control group of 72 patients who underwent elective AAA repair revealed an increased incidence of inflammatory aneurysm and female gender among our study group. The symptomatic patients had larger aneurysms (6.5 vs. 5.6 cm, p < 0.05) and required more intraoperative transfusions. Intensive care unit and hospital stay was longer in the symptomatic patients (p < 0.001); morbidity was markedly increased (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198945 TI - Experimental study of determinants of aneurysmal expansion of the abdominal aorta. AB - The natural history and the factors determining the expansion of aneurysms have not been elucidated. To study the respective roles of elastolysis, collagenolysis, inflammatory cells, and hypertension in the pathogenesis of aneurysms, two previously described in vivo experimental models were used. An isolated segment of the abdominal aorta was infused with 15 units of pancreatic elastase. The maximal diameter of the aorta was measured before and after infusion and the isolated aorta was excised for classic histologic and immunohistologic studies. Twelve hours after the infusion of elastase the mean diameter of the aorta increased by 30%. The aorta had a cylindric form and only collagen fibers remained. Two and a half days after the infusion the aorta was spherical in shape and the diameter increased by 300% (3.09 +/- 0.08 mm) (p < 0.05). The entire aortic wall was invested by inflammatory cells. Six days after infusion the diameter increased by 421% (4.38 +/- 0.03 mm) (p < 0.05), and immunohistochemical staining showed numerous T lymphocytes and macrophages. Between 6 and 12 days, after perfusion inflammation decreased, the final diameter was 4.23 +/- 0.14 mm (not significant). Sixteen rats had thioglycollate and plasmin infusion, which are nonspecific activators of inflammation. Nine days after infusion the diameter of the aorta had increased by 288%; the elastic fibers of the media were fragmented and rare and the entire aortic wall was invaded by inflammatory cells, predominantly macrophages. The diameter of the aorta increased progressively. Two groups of 17 hypertensive rats (renovascular and spontaneous hypertension) received an aortic infusion of 15 units of pancreatic elastase. Elastolysis overlapped the limits of the infusion and inflammation persisted after 2 weeks. The mean diameter of the aorta (F = 11, p < 0.01) and the mean length of the aneurysms (F = 11.2, p < 0.001) were significantly increased. This study demonstrates that elastolysis and especially collagenolysis are determinants of aneurysmal expansion. Inflammation may be a promoting factor in the degradation of the aortic wall. Hypertension increases the hemodynamic stress to the aorta and activates mural inflammation. PMID- 8198947 TI - Immediate and long-term results of carotid endarterectomy for asymptomatic high grade stenosis. AB - We examined the operative risks and long-term results of carotid endarterectomy for asymptomatic patients in terms of stroke, death, and recurrent stenosis. The results of a nonrandomized study with a follow-up of 1 to 104 months (mean 46 months) is reported. A tertiary referral center served as the setting for this report. One hundred consecutive patients with severe but asymptomatic carotid artery stenosis out of a total of 514 patients undergoing carotid endarterectomy were entered into this study. The severity of carotid disease was determined by duplex scanning and confirmed arteriographically. No patients were lost to follow up after surgery. Eighty-nine operations (77%) were done under cervical block anesthesia and all arteries were closed with saphenous vein patches. Life-table analysis showed that the stroke-free rate at 5 years was 96.3% with an ipsilateral stroke-free rate of 98.2%. The 5-year overall survival rate was 78.2% with a stroke-free survival rate of 75%. Carotid endarterectomy can be performed safely for asymptomatic patients believed to be at risk for stroke. The potential for early death due to myocardial disease, late stroke, and recurrent stenosis do not justify advising patients against undergoing prophylactic carotid endarterectomy for asymptomatic high-grade stenosis. PMID- 8198946 TI - Abdominal aortic aneurysm surgery: survival and quality of life in patients requiring prolonged postoperative intensive therapy. AB - The goal of this study was to identify patients who need longer care in the ICU (more than 48 hours) following abdominal aortic aneurysm (AAA) surgery and to evaluate the influence of perioperative complications on short- and long-term survival and quality of life. AAA surgery was performed in 553 patients, 51 (9%) of whom died within the first 48 hours. Of the 502 patients who survived for more than 48 hours, 109 required ICU therapy for more than 48 hours, whereas 393 patients were in the ICU for less than 48 hours. The incidence of preoperative risk factors was similar for the two groups. The cumulated survival rates for the two groups were 68% and 92% at 1 months, 52% and 88% at 1 year, and 60% and 33% at 6 years, respectively. This significant difference was primarily related to renal, pulmonary, and cardiac complications. However, assessment of the most severe complications and risk factors combined failed to permit identification of patients in whom the perioperative survival rate was 0%. Even 20% of patients with multiorgan failure survived for 6 months. Of those patients who needed ICU therapy for more than 48 hours, 41 (38%) were alive at the end of 1988. In response to a questionnaire, 78% stated that their quality of life had improved or was unchanged after surgery and had resumed working. These data justify a therapeutically aggressive approach, including ICU therapy following AAA surgery, despite failure of one or more organ systems. PMID- 8198948 TI - Influence of perioperative storage solutions on long-term vein graft function and morphology. AB - It has been shown that suboptimal preparation of a vein graft prior to its insertion results in immediate morphologic and functional damage to the endothelial cells but not to the underlying smooth muscle cells. However, little is known about whether such perioperative injury to the vein grafts influences the subsequent development of intimal hyperplasia and smooth muscle cell contractility. This study examines the influence of storage in saline solution or Ringer's lactate on the development of intimal hyperplasia and vasomotor function in experimental vein grafts. Twenty-six New Zealand white rabbits had a carotid vein bypass graft performed after the veins had been immersed (15 minutes) in either heparinized saline solution (Sal; n = 13) or Ringer's lactate (RL; n = 13), and each group was harvested after 28 days for either histologic (n = 8) or functional studies (n = 5; four 5 mm rings/graft). Saline storage of the vein graft resulted in a 38% increase in the thickness of the intimal hyperplasia (113 +/- 2 vs. 83 +/- 2 microns, Sal vs. RL; mean +/- SEM; p < 0.05) without a change in medial thickness (87 +/- 5 vs. 86 +/- 8 microns, Sal vs. RL; p > 0.05). The two sets of vein grafts showed no difference in sensitivity to norepinephrine, serotonin, and bradykinin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198949 TI - Suppression of intimal hyperplasia in a rabbit model of arterial balloon injury by enalaprilat but not dimethyl sulfoxide. AB - Intimal hyperplasia appears to result from the deposition of collagen and matrix by medial myofibroblasts, which are stimulated in response to vascular injury. We hypothesized that pharmacologic inhibitors of fibroblast proliferation would suppress the development of intimal hyperplasia. We evaluated the effect of two agents known to inhibit fibroblast proliferation in vitro: enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor, and dimethyl sulfoxide (DMSO), an organic solvent. Thirty-five New Zealand white rabbits underwent standardized balloon catheter injury of the left common carotid artery. Experimental groups received daily intramuscular injections of the following: group I (n = 15), saline solution; group II (n = 10), 0.07 mg/kg enalaprilat; and group III (n = 10), 2 ml/kg of a 25% by weight DMSO solution. Injections were started 1 day prior to injury and continued 5 days a week for 8 weeks. Carotid arteries were perfusion-fixed at 12 weeks and cross-sectioned for measurement by planimetry. Intimal hyperplasia was measured as the ratio of the absolute area of intimal hyperplasia to the normalized area enclosed by the internal elastic lamina (IH/IEL) and was expressed as a percent. Mean values for IH/IEL were as follows: group I (control), 20.6 +/- 2.3%; group II (enalaprilat), 9.5 +/- 0.7%; and group III (DMSO), 17.6 +/- 2.6%. Enalaprilat-treated animals demonstrated a statistically significant suppression of intimal hyperplasia compared with controls (p < 0.01, ANOVA, Student's t test), whereas the DMSO-treated group did not. We conclude that enalaprilat is effective in suppressing the development of intimal hyperplasia in this model of arterial injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8198950 TI - Hemodynamic sequelae of combined arteriovenous injury in an experimental canine hindlimb model: venous ligation vs. repair. AB - The hemodynamic effects of combined venoarterial injury and stasis were studied in the hindlimbs of 10 dogs. Femoral arterial blood flow and pressure, peripheral venous pressure, and peripheral resistance were measured after the restoration of blood flow following venoarterial injury and a 4-hour period of occlusion for up to 72 hours. In one limb of each animal both the artery and vein were repaired, whereas only the artery was repaired in the other limb and the vein was ligated. Arterial blood flow was similar in both groups but was significantly diminished from baseline for the first 30 minutes after restoration of blood flow, but then it became significantly reduced in the limbs with venous ligation when compared with values in those with venous repair. By 72 hours the flow on both sides returned to control values. Peripheral venous hypertension and edema occurred in all 10 limbs with venous ligation and persisted for the 72-hour experimental period. In the 10 limbs with venous repair, edema occurred in four and venous hypertension in none. The peripheral resistance was elevated on both sides; this elevation persisted for 75 minutes and then dropped to control values. None of the repaired arteries and only one repaired vein thrombosed during the experiment. Combined venous and arterial occlusion for 4 hours reduced both the amount of arterial flow and its subsequent rate of increase compared with changes seen after release of an acute venous occlusion. The rate of increase was enhanced by repair of the affected venous segment compared with simple venous ligation. PMID- 8198951 TI - Infusion methods for determination of peripheral resistance: influence of infused medium and back pressure. AB - It has been suggested that peripheral vascular resistance (PR), measured intraoperatively, can predict the outcome of infrainguinal reconstructions. There is, however, a great deal of variability in design and predictive value with this method, and it is prone to technical difficulties and possible errors. The present study evaluated the influence of the choice of infusion medium and the back pressure on PR as measured by the infusion technique. In a porcine model of experimentally induced stenosis, standard PR (calculated by the pressure difference across the stenosis and the Doppler volume flow) was compared with PR based on infusions of blood or saline solution. With blood as the infusion medium there was a significant correlation between the PR and the standard values (r = 0.795, p = 0.0005), whereas there was no correlation when saline solution was infused (r = 0.067, p = 0.345). Subtracting the back pressure resulted in a slight improvement in the correlations between standard PR and PR measured after infusion of blood but not saline solution. In summary, blood should be used as an infusion medium in methods of PR determination, but the influence of back pressure remains uncertain. PMID- 8198952 TI - Rural vascular trauma: a twenty-year review. AB - A 20-year review documented 248 vascular injuries in 210 patients from principally rural areas. The average time between injury and treatment from 1970 to 1983 was 6 hours. Between 1983 to 1990, when 46% of patients were transported by helicopter, the average delay was 4 hours. Blunt trauma (41%, with 29% motor vehicle accidents and 12% farm/industrial accidents) caused the most severe injuries and accounted for most amputations (89%) and deaths (80%). All of the blunt trauma patients had associated injuries. Penetrating injuries occurred in 59% of the patients and accounted for 11% of the amputations and 20% of the deaths. Extremity vessels were injured 73% of the time (upper extremity, 47%; lower extremity, 26%). Eighty-seven percent of the vessels injured were arteries and 13% were major venous injuries. Preoperative arteriograms were obtained in 30% of our patients. Vascular injury was determined in the others at the time of operative exploration. Vascular repair included direct anastomosis or lateral suture repair (51%), autogenous vein graft (16%), synthetic graft (6%), and ligation (19%). Primary amputation and thrombectomy were other (8%) initial treatments. In the past 10 years concomitant major peripheral venous injuries were repaired in six patients (one amputation) and ligated in one patient (no amputation). The mortality rates (4.8% total) for patients with blunt and penetrating trauma were 9.3% and 1.6%, respectively. Survival rates have not improved since the implementation of a helicopter transport system in 1983, but the amputation rate declined from 18% to 7%. PMID- 8198953 TI - Changing practice patterns in peripheral arterial disease. AB - The development of interventional radiologic techniques during the past decade has changed our approach to the treatment of lower extremity peripheral arterial disease (LE-PAD). Balloon and laser-assisted angioplasty, atherectomy (rotary and directional devices), stent implantation, and thrombolysis as well as combinations of all of these approaches, at times with concomitant or secondary surgery, have been used in our institution. A review of our practice patterns during the past 5 years was performed to analyze changing attitudes and results with these newer techniques. All new patients seen in consultation for LE-PAD during three alternate years were reviewed with regard to demographics, initial complaints, initial treatment modality, initial outcome, indications for and results of secondary treatment, and ultimate outcome (at 1 year). The 603 patients were seen during the following three 12-month periods: 1987 to 1988, 1989 to 1990, and 1991 to 1992. An intention-to-treat analysis revealed (1) the number of patients seen for peripheral arterial disease has increased steadily; (2) in the last year more were initially treated with intervention as the primary modality; (3) the results of such catheter-based procedures improved only slightly over this 5-year period, despite our learning curve and the fact that we discarded several ineffective interventional approaches; (4) the fraction of patients primarily operated on and the excellent results of surgery have not changed; and (5) the number of operations for proximal (aortoiliac) disease has decreased markedly, with a corresponding increase in distal reconstructions. The evolution of our current approach to the treatment of LE-PAD is based on this continuing experience. PMID- 8198954 TI - Stationary arterial wave phenomena. AB - The case of a 38-year-old woman who was struck by an automobile is presented. The workup for lower extremity injuries revealed stationary arterial waves. Recognition of this arteriographic finding may avoid unnecessary confusion or exploration. PMID- 8198955 TI - Popliteal pseudoaneurysm as a complication of an adjacent osteochondroma. AB - A 19-year-old man presented to our institution with a 4-month history of a pulsatile mass in the left popliteal fossa. Evaluation including plain x-ray films, MRI, and arteriography revealed a pseudoaneurysm associated with an underlying exostosis of the distal femur. The pseudoaneurysm was repaired with a saphenous vein patch and the exostosis was excised. This case is reported in conjunction with an extensive review of the literature, which yielded only 25 similar cases reported in the English language since 1953. The majority of cases involved young men (20/26), whose ages ranged from 9 to 45 years (mean 20 years). Fifteen of the 26 cases involved isolated exostoses, and in less than half (12/26), antecedent trauma was identified as a cause of the pseudoaneurysm. The origin of exostoses and their relationship to popliteal pseudoaneurysms are discussed. Repair of the pseudoaneurysm and excision of the involved exostosis are recommended. PMID- 8198956 TI - Pelvic ischemia following aortoiliac reconstruction. AB - Clinically evident compromise of parietal or visceral pelvic function secondary to interruption of pelvic blood flow occurs infrequently after aortoiliac reconstruction. Certain patterns of aortoiliac or occlusive aneurysmal disease or graft infection may require exclusion of the hypogastric or profunda femoral arteries. In these situations collateral blood flow or retrograde iliac flow may be insufficient to perfuse the pelvis and may cause ischemia. We present three cases of postoperative pelvic ischemia and describe our efforts to restore pelvic perfusion. PMID- 8198957 TI - Primary aortoenteric fistula: Part II. Primary aortoesophageal fistula. PMID- 8198958 TI - Left retroperitoneal approach to the aorta and its branches: Part I. PMID- 8198959 TI - Dracunculiasis. Global surveillance summary, 1993. PMID- 8198960 TI - Analysis of the therapeutic gain in the treatment of human osteosarcoma microcolonies in vitro with 211At-labelled monoclonal antibody. AB - Microcolonies were obtained by culturing cells of two human osteosarcoma lines (OHS and KPDX) and one human melanoma line (WIX-c) for either 24 or 72 h. The microcolonies were treated with either alpha-particle radiation emitted by the 211At-labelled monoclonal antibody (MAb) TP-3 or external beam X-rays. Survival of microcolonies was assayed by colony formation. Therapeutic gain factor (TGF) values were calculated for two survival levels, 50% and 20% microcolony regeneration (i.e. at least one cell in 50% or 20% of the colonies survived the treatments). The TGF values were affected by the specific activity of the 211At MAb conjugate, the antigen expression of the cells and the size and growth pattern of the microcolonies. Treatment with 211At-TP-3 gave TGF values that varied from 1.3 +/- 0.4 to 4.5 +/- 0.7 (mean +/- s.e.). The antigen-rich OHS cell line had on average 1.6 times higher TGF than the antigen-poor KPDX cell line. The TGF increased significantly with colony size for the densely packed colonies of the KPDX cell line but not for the OHS cell line, which had colonies with cells growing in a more scattered pattern. Control experiments with the two non specific 211At forms, free 211At and 211At-labelled bovine serum albumin, gave TGF values from 0.6 +/- 0.1 to 1.0 +/- 0.3. This study suggests that in vivo evaluation of 211At-MAbs using relevant tumour models is desirable. PMID- 8198961 TI - Expression of transforming growth factor beta mRNA isoforms in human breast cancer. AB - Using an RNAse protection assay, expression of messenger RNA for isoforms of TGF beta was determined in a series of breast cancers. Of 50 tumours, 45 (90%) expressed TGF-beta 1 mRNA, 39 (78%) expressed TGF-beta 2, and 47 (94%) expressed TGF-beta 3. Patterns of expression varied between different tumours: 37 (74%) cancers expressed all three TGF-beta isoforms, ten (20%) expressed only two isoforms and two expressed TGF-beta 1 alone. One sample showed no evidence of TGF beta mRNA expression. Although most breast cancers expressed mRNA for at least one isoform of TGF-beta, there were differences in patterns of mRNA expression between individual tumours. The relatively small number of tumours examined precluded detailed analysis between expression and other clinical parameters, but a significant association was identified between one aspect of isoform expression and lymph node status, in that the majority of tumours expressing all three isoforms were associated with lymph node involvement, whereas tumours without one or more isoform were usually lymph node negative (P = 0.025 by Fisher's exact test). PMID- 8198962 TI - Modulation of the mevalonate pathway and cell growth by pravastatin and d limonene in a human hepatoma cell line (Hep G2). AB - Modulation of cell growth by a combination of pravastatin [a 3-hydroxy-3 methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor] and d-limonene (an inhibitor of protein isoprenylation) was studied using Hep G2, a human hepatoma derived cell line. Pravastatin, at 0.1 mM, produced 85% inhibition of cholesterol biosynthesis in Hep G2 cells. The combination of 0.1 mM pravastatin and 1.0 mM d limonene had no further effect on the reduction seen with pravastatin alone. Addition of 0.1 mM pravastatin or 1.0 mM d-limonene did not significantly suppress DNA synthesis by the cells, whereas the combination suppressed it to 50% of the control level. Production of m-p21ras was markedly decreased to 35% of the control level by the combination of these two inhibitors. Both the reduction by pravastatin of farnesylpyrophosphate as substrate for protein:farnesyl transferase and inhibition of protein farnesylation by d-limonene seem to be responsible for the profound suppression of m-p21ras formation in the cells. However, dolichol synthesis was not suppressed by the combination of these inhibitors. In human fibroblasts, the combination suppressed m-p21ras production but not DNA synthesis. These findings suggest that the combination of pravastatin and d-limonene acts on cancer cell growth through inhibition of the post translational processing of cellular proteins including p21ras, rather than through the suppression of cholesterol and dolichol biosynthesis. Thus, the combination of an HMG-CoA reductase inhibitor and an inhibitor of protein isoprenylation offers potential as a new approach for cancer therapy. PMID- 8198963 TI - Helix pomatia agglutinin binding in human tumour cell lines: correlation with pulmonary metastases in nude mice. AB - The extent of lectin binding by three human melanoma (LOX, FEMX-1 and SESX) and two sarcoma lines (MHMX and OHSX) was related to their potential for experimental metastasis formation in athymic nude mice. The Helix pomatia agglutinin (HPA), which recognises the N-acetyl-D-galactosamine ligand, showed differential binding to the cell lines in a manner that correlated with their ability to give lung colonies after i.v. injection in the mice (P < 0.005). The degree of HPA binding and lung colony formation of the cell lines studied was ranked in the following order, LOX > MHMX > OHSX > SESX > FEMX-I. Similar patterns were not observed with the other lectins used in this study (WGA, Con A, PNA and UEA-I). The high HPA reacting LOX melanoma line shows extensive pulmonary metastatic formation with no extrapulmonary colonies, whereas the low HPA reacting FEMX-I cells give only extrapulmonary metastases with no detectable colonies in the lungs. Precoating of tumour cells with HPA prior to injection did not reduce the ability of cells to give pulmonary metastases, suggesting that the HPA epitope was not functionally associated with the pulmonary metastatic potential observed in nude mice. These findings support recent human studies of a correlation between HPA binding and incidence of metastasis, however, our data indicate that there is no causal relationship. Further analyses are required to identify the specific HPA-binding glycoconjugates that may be involved. PMID- 8198964 TI - Splanchnic blood flow changes in the presence of hepatic tumour: evidence of a humoral mediator. AB - Intrahepatic tumour is associated with alterations in splanchnic haemodynamics. To investigate the hypothesis that these are the result of a circulating vasoactive agent, rat small bowel segments were cross-perfused with arterial blood from groups (n = 12) of paired tumour-bearing (intrahepatic HSN sarcoma) and control rats. The vascular resistance of the segment was significantly greater during perfusion by tumour-bearing animals (91.6 mmHg ml-1 min, s.e. 21.5, vs 51.7 mmHg ml-1 min, s.e. 7.4, P < 0.05), suggesting that intrahepatic tumour may be associated with a circulating vasoactive agent. A similar mechanism may underlie changes in the hepatic perfusion index in patients with liver metastases. PMID- 8198965 TI - Three-dimensional computerised analysis of epithelial cell proliferation in the gastrointestinal tract. AB - This study describes a new technique for the visualisation and quantitation of glandular epithelial cell proliferation in gastrointestinal mucosa using computerised three-dimensional reconstruction. The tissue used in this study was colorectal biopsy tissue infiltrated in vitro with bromodeoxyuridine (BrdU), although the method could be applied to any gastrointestinal site labelled with any specific marker for cell proliferation. The method is as follows. Five-micron thick serial sections (> 100) were cut from colorectal biopsies infiltrated in vitro with BrdU. After labelling all the sections for BrdU-positive cells using standard immunohistochemistry, colorectal glands were identified which were completely sectioned within the series. Each microscopic image of the sectioned gland was orientated, digitised and stored using a Kontron image analyser. On each of the stored images, the crypt profile, the positive cells and the negative cells were interactively marked and digitally stored. Using three-dimensional (3 D) reconstruction software, the outer surface of the crypt, the total positive and the total negative fractions could be viewed in three dimensions. The total BrdU-positive cell number could be automatically calculated for the complete crypt or, alternatively, compartmental analysis of the labelling pattern within the crypt could be obtained. This represents a powerful technique: it does not require orientation, it can be carried out on complex glandular structures and is not affected by the biases involved in measuring labelling indices from single tissue sections. PMID- 8198966 TI - Dual immunocytochemical analysis of oestrogen and epidermal growth factor receptors in human breast cancer. AB - Recent studies have demonstrated a consistent inverse relationship between oestrogen receptor (ER) and epidermal growth factor receptor (EGFR) levels in female human breast cancer. Serial cross-section studies have suggested that separate populations of ER+/EGFR- and ER-/EGFR+ cancer cells exist in tumours deemed by immunocytochemical assay (ICA) to be positive for both. We have developed a dual ICA that is able to stain for both ER and EGFR on a single 5 microns frozen section sample of breast tissue. Twenty-two samples of female human breast cancer tissue that exhibited positivity for ER and EGFR by ER-ICA using the H222 monoclonal antibody and EGFR-ICA using the EGFR1 monoclonal antibody underwent the dual ICA. There was a significant correlation in receptor positivity between the single and dual assays for both ER (rs = 0.801, P < 0.001) and EGFR (rs = 0.831, P < 0.001). Individual cancer cells exhibited one of three staining patterns: nuclear staining only (ER+/EGFR-), membrane-associated and cytoplasmic staining only (ER-/EGFR+) or no staining (ER-/EGFR-). No cancer cells exhibited both nuclear and membrane/cytoplasmic staining. This is the first description of a simultaneous dual immunocytochemical assay system for ER and EGFR in clinical breast cancer specimens. The results suggest that ER and EGFR expression are mutually exclusive within an individual breast cancer cell in vivo with separate populations of ER+/EGFR- cells, ER-/EGFR+ cells and ER-/EGFR- cells coexisting. PMID- 8198967 TI - Anti-tumour activity of low-toxicity lipopolysaccharide of Bordetella pertussis. AB - A lipopolysaccharide (BP-LPS) isolated from killed Bordetella pertussis (Tohama strain) was determined to have low toxicity based on the mortality and decrease in body weight of BP-LPS-injected mice. BP-LPS, administered intradermally or intraperitoneally, clearly inhibited the growth of an MM46 murine mammary carcinoma. When compared with a toxic Escherichia coli-derived LPS, BP-LPS displayed excellent anti-tumour activity against MH134 hepatoma and Meth A fibrosarcoma. As part of a combined chemotherapy/immunotherapy regimen, BP-LPS also seemed to prolong the lifespan of mice inoculated with Lewis lung carcinoma. BP-LPS thus appears to have valuable characteristics as an anti-tumour agent. PMID- 8198968 TI - Tumorigenicity of a combination of psoriasis therapies. AB - Coal tar, a tumour initiator, and dithranol, a tumour promoter, are used in the treatment of psoriasis. Topical treatment of mice with pharmaceutical formulations of these two agents, at therapeutic doses, induced skin papillomas in a classical two-stage carcinogenesis protocol, while treatment with either agent alone did not. This finding has implications for the use of both agents in combination in the treatment of psoriasis. PMID- 8198969 TI - Functional role of IL-2 receptors on tumour-infiltrating lymphocytes. AB - This study was undertaken to investigate the pathways involved in the interleukin 2 (IL-2)-driven growth of tumour-infiltrating lymphocytes (TILs). For this purpose, TIL lines and freshly isolated TILs obtained from 16 patients with solid cancer (three melanoma, seven primary colorectal carcinoma, four hepatic metastases from colorectal cancer and two lung cancer) were evaluated for (a) expression of IL-2 receptor (IL-2R) both at the RNA level and on the cell surface by flow cytometric analysis and (b) their proliferative activity in response to IL-2 and the role of IL-2R subunits in the IL-2-driven TIL growth. Northern blot analysis showed that TILs express a strong message for both the p55 and the p75 IL-2R. Accordingly, flow cytometric analysis demonstrated that TILs bear both IL 2R chains. TILs cultured in vitro in the presence of rIL-2 were able to proliferate in response to different concentrations of this cytokine. Monoclonal antibodies (MAbs) specifically recognising the p55 and p75 IL-2R chains (anti-Tac and TU27 respectively) exhibited a marked inhibitory effect on IL-2-driven growth when added individually or in appropriate combinations. Our results demonstrated that TILs are equipped with a fully functional IL-2 receptor system, thus suggesting the involvement of this structure in the activation and expansion of TILs following immunotherapy with IL-2. PMID- 8198970 TI - Abnormalities of the p53 MDM2 and DCC genes in human leiomyosarcomas. AB - In this study we have screened a series of 29 primary leiomyosarcomas for abnormalities of both the p53 gene and the MDM2 gene, which encodes a p53 associated protein. SSCP (single-strand conformation polymorphism) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA were used to establish that 6/29 tumours possessed point mutations of the p53 gene. Using a monoclonal antibody that recognises the p53 protein in immunohistochemical staining experiments, we observed overexpression of the p53 protein in five of the six tumours containing point mutations in the p53 gene. Southern analysis of tumour DNA revealed that 2/29 tumours demonstrated amplification of the MDM2 gene. When considered together, these results indicate that alterations in both the p53 gene and MDM2 gene are important in the development of a significant minority of leiomyosarcomas. In addition, we have demonstrated a significant association between the presence of abnormalities of the p53 gene or MDM2 genes in leiomyosarcomas and a more advanced clinicopathological stage (P = 0.03). We have also examined the role of the DCC tumour-suppressor gene in the development of human soft-tissue tumours in a variety of histological types. Except for evidence of a rearrangement in a single leiomyosarcoma cell line, SK-UT-1, we have found no direct evidence to support a role for mutation of the gene in the development of human soft-tissue tumours. PMID- 8198971 TI - Production of endothelin-1 and thrombomodulin by human pancreatic cancer cells. AB - Analysis of bioactive substances produced by cancer cells is one approach to understanding the biological features of human cancer. One of these bioactive substances is endothelin (ET)-1, a peptide with potent vasoconstrictive activity produced by vascular endothelial cells. We have previously reported the production of ET-1 by several types of human cancer, especially pancreatic cancer cells. To elucidate whether these cancer cells might share biological characteristics with vascular endothelial cells, we investigated the production of three ET isoforms in pancreatic cancer cells, using a specific radioimmunoassay. Further, we also investigated whether these cells produce thrombomodulin (TM), another product of endothelial cells functioning as a modulator of procoagulant activity. ET-1 was detected in 11 of 12 pancreatic cancer cell lines (92%) while ET-2 and ET-3 were detectable in only one cell line. Gel filtration analysis confirmed the presence of ET-1. Moreover, TM was detected in the cell lysates of 11 of the 12 cell lines (92%) and it was released into the culture medium in the majority (58%) of these cell lines. TM mRNA was also detected in these cells. In addition, TM was demonstrated immunocytochemically along the cell surface. These results suggest that pancreatic cancer cells share two characteristics with endothelial cells: the production of ET-1 and TM. PMID- 8198972 TI - Spontaneous in vitro differentiation of a myoepithelial cell line (PA 16/23) from a pleomorphic adenoma of the parotid gland is associated with reduced production of the autocrine growth factor interleukin 6. AB - A myoepithelial cell line (PA 16/23) was derived from a pleomorphic adenoma of the parotid gland. PA 16/23 cells have light microscopic, immunophenotypical and ultrastructural features of immature myoepithelial cells, i.e. they are of fusiform or stellate shape and show keratin and actin cytofilaments located mainly in the perinuclear cytoplasm, desmosomes and tracts of basal lamina. The PA 16/23 cells grew actively and expressed mRNA for and produced interleukin 6 (IL-6) which was released into the culture medium. This cytokine, in turn, acted as an autocrine growth factor on the cells. PA 16/23 cells also expressed high affinity IL-6 receptors. In these cells, both IL-6 production and proliferation could be modulated by exogenous stimulants, such as IL-6 itself, IL-1, IL-4, tumour necrosis factor alpha, interferon gamma and lipopolysaccharide. From the 40th culture passage onwards, the PA 16/23 cells ceased to grow, either spontaneously or in response to exogenous stimulants. Moreover, they strongly reduced IL-6 production, and underwent morphological differentiation into more mature myoepithelial cells, with an increased amount and a different arrangement of the keratin and actin cytofilaments, which formed thick bundles in the peripheral cytoplasm. These findings suggest a role for IL-6 in modulating the proliferation and, possibly, the differentiation of the PA 16/23 cells. PMID- 8198973 TI - Limited heterogeneity in the T-cell receptor V-gene usage in lymphocytes infiltrating human colorectal tumours. AB - The presence of T lymphocytes in solid tumours may reflect an ongoing immune response against the transformed cells. We have used polymerase chain reaction (PCR) technology to investigate the T-cell receptor variable-region gene (V-gene) usage in freshly isolated tumour-infiltrating lymphocytes (TILs) to look for a possible oligoclonality of T cells in the tumour area. We used 19 different V beta-family-specific primers. Peripheral blood lymphocytes and lamina propria lymphocytes from the same patients were also tested by PCR. Our results demonstrate a limited heterogeneity in the V-gene usage of TILs from seven patients with colorectal cancers, suggesting a local antigen-driven immune response at the tumour site. PMID- 8198974 TI - Magnetic resonance spectroscopic studies on 'real-time' changes in RIF-1 tumour metabolism and blood flow during and after photodynamic therapy. AB - Magnetic resonance spectroscopy (MRS) in situ was used to study changes in 31P metabolism occurring during and after treatment of murine RIF-1 tumours with photodynamic therapy (PDT). Tumours were irradiated using a fibreoptic light delivery system while the mice were in position within the magnet. Changes in 31P MRS were observable during and immediately after treatments of several minutes' duration. Both the extent and duration of the increase in the Pi/total ratio were light dose dependent. The effect on the metabolism was also affected by the time interval (TL) between administering the photosensitiser disulphonated phthalocyanine, (A1S2Pc) and the light. With a dose of 50 J the increase in Pi/total was much faster when TL was 1 h than when TL was 24 h. This difference in rate probably reflects differences in the distribution of A1S2Pc within the tumour. Significant decreases in pH were only seen after a light dose of 50 J when TL was 1 h. Blood flow measurements using deuterium uptake were also carried out using MRS. These experiments showed that for a dose of 50 J the level of blood flow was reduced by approximately 90% of the control value within 10 min from the end of the 8 min light treatment. This occurred irrespective of the value of TL. The data indicate that it is possible to observe very early changes in 31P metabolism that can be attributed to direct cellular damage as opposed to the later changes indicative of overall tumour hypoxia caused by vascular damage. PMID- 8198975 TI - Clinical stage 1 non-Hodgkin's lymphoma: long-term follow-up of patients treated by the British National Lymphoma Investigation with radiotherapy alone as initial therapy. AB - A retrospective analysis was performed of 451 adult patients with clinical stage 1/1E non-Hodgkin's lymphoma treated initially with radiotherapy alone. Histopathologically 208 patients had low-grade disease and 243 patients high grade disease. The complete remission (CR) rate was higher in patients with low grade disease (98%) than in those with high-grade disease (84%) (P < 0.0001). The relapse rate was similar in both histological categories, and relapse usually occurred within 5 years. The resulting overall actuarial percentage of patients achieving CR and remaining disease free (at 10 years) was 47% in patients with low-grade disease and 45% for those with high-grade disease. Salvage therapy was frequently successful in younger patients, and the overall cause-specific survival at 10 years was 71% for low-grade disease and 67% for high-grade disease. In those patients under 60 years of age at diagnosis, the overall cause specific survival at 10 years was 84% and 80% for those with low-grade and high grade disease respectively. These long-term results in young patients with clinical stage 1 disease are encouraging, and it will be difficult to demonstrate improved survival with initial chemotherapy either with or without radiotherapy, until new prognostic factors are found to identify poor-risk patients. PMID- 8198976 TI - Late mortality and levamisole adjuvant therapy in colorectal cancer. AB - Beginning in 1975, 78 patients with resected stage B and C colorectal carcinoma were randomly assigned (2:1) to receive either levamisole 2.5 mg kg-1 day-1 given for 2 days every week for 18 months or placebo therapy in the same schedule. Pretreatment characteristics (age, gender, disease site, CEA and stage) and the pattern of follow-up were similar in both groups. For the first 5 years following randomisation, relapse-free survival and overall survival were similar in the two treatment groups. Subsequently, excess late mortality was associated with levamisole group assignment. Consequently, overall survival was somewhat greater in the placebo group than in the levamisole group, 68% vs 38% (P < 0.08). For patients surviving 5 years from randomisation, subsequent survival favoured placebo over levamisole (100% vs 57%; P < 0.03). The absolute numbers of deaths were 27 in the levamisole group (19 definitely cancer related) and seven in the group placebo (five definitely cancer related). This long-term result seen with a more intensive adjuvant levamisole dose and schedule suggests: (1) other levamisole adjuvant trials in patients with colorectal cancer should be examined for long-term outcome; (2) future trials utilising the even higher levamisole dosage required for clinical immunomodulation should proceed cautiously. PMID- 8198977 TI - Case-control study of gastric cancer screening in Venezuela. AB - A screening programme for early gastric cancer was introduced in the state of Tachira, Venezuela, in 1980. Screening was performed by photofluorography, using two mobile units. The efficacy of this programme in reducing mortality from stomach cancer was evaluated by means of a case-control study. Cases were 241 individuals who died from stomach cancer in the period 1985-89. Ten live controls per case were drawn from the electoral rolls, matched by sex, age and residence. Exposure to the screening examination of cases and controls was assessed through individual linkage with the programme's centralised database. After the exclusion of examinations occurring within the 6 months preceding the case's diagnosis, the odds ratio (OR) of dying from stomach cancer for those screened was 1.26 (CI 0.83 1.91) and the OR in females was lower than in males: 0.77 (CI 0.33-1.78) and 1.52 (CI 0.94-2.47) respectively. Odds ratios associated with years since last test and number of tests did not differ significantly from 1. These results show the inefficacy of the programme in reducing mortality from gastric cancer in the area. In an attempt to determine whether this result was due to selection bias, an analysis restricted to subjects who had been screened at least once was performed. When examinations occurring after an index date at various intervals before the case's diagnosis were excluded, the screening test appeared to protect from death, although confidence intervals of the odds ratios are large, for example OR = 0.47 (CI 0.24-0.98) when excluding tests within 1 month. PMID- 8198978 TI - DNA ploidy and proliferative activity (S-phase) in childhood soft-tissue sarcomas: their value as prognostic indicators. AB - The value of DNA ploidy as a prognostic indicator is well established in many cancers, but recent studies in childhood rhabdomyosarcoma (RMS) have been contradictory. In a retrospective study of 128 cases of soft-tissue sarcoma (STS) diagnosed since 1980, the prognostic value of clinical, histological and flow cytometric parameters was compared, using univariate and multivariate methods. Eighty-one RMSs, 18 extraosseous Ewing's (EOE)/peripheral neuroectodermal tumours (PNETs) and 29 other non-RMS STSs were histologically and clinically reviewed. Five year actuarial survival was 63.4% for all STSs and 69.4% for RMSs. Paraffin embedded tissue blocks were available for flow cytometry in 90 cases. Of the RMSs, 65.5% were aneuploid [DNA index (DI) > 1.1] compared with 23% of the EOE/PNETs and 31% of non-RMS STSs. Median S-phase was also significantly higher in RMSs (17.0%) than in other STSs (10.8%) (P = 0.0023). Univariate analysis in RMSs showed that stage, ploidy status, S-phase, site and tumour size all had a significant impact on survival. In multivariate analysis of 59 cases of RMS, one clinical and two flow cytometric parameters were independently associated with poor prognosis. These were stage (IV), nonhyperdiploidy (DI < 1.10 and > 1.8) and a high rate of proliferative activity (S-phase > 14.0%). These results confirm that ploidy and S-phase are important new prognostic indicators in rhabdomyosarcoma. PMID- 8198980 TI - The relationship between serum p53 autoantibodies and characteristics of human breast cancer. AB - Sera from 182 newly diagnosed breast cancer patients were assayed for antibodies to p53 using an enzyme-linked immunosorbent assay (ELISA) method, and antibodies were detected in 48 (26%) compared with 1 out of 76 (1.3%) normal control volunteers (P = 0.0001). In breast cancer patients, autoantibodies were found in all stages of disease progression: carcinoma in situ, primary invasive breast cancer and in metastatic disease. In the subset of patients in whom sequential sera were assessed over a 6 month period, changes in the p53 antibody titres were observed. The presence of antibodies to p53 correlated positively with high histological grade (P = 0.0012) and a history of second primary cancer (six positive out of eight cases). The incidence of autoantibodies was lower in those patients with a first-degree relative with breast cancer (P = 0.046). Out of 68 patients, there was a significant correlation between positive p53 autoantibody status and the detection of p53 protein in the tissue sections by immunocytochemistry (P = 0.002). In the seronegative patients, positive p53 tumour staining was strongly associated with a family history of breast cancer (P = 0.009). The p53 protein overexpressed in heritable breast cancers may therefore be less immunogenic. The presence of p53 autoantibodies provides important additional information to immunochemistry and may identify patients with aggressive histological types of breast cancer. PMID- 8198979 TI - Subcutaneous low-dose recombinant interleukin 2 and alpha-interferon in patients with metastatic renal cell carcinoma. AB - A double-institution phase II study was performed in patients with metastatic renal cell carcinoma treated subcutaneously (s.c.) with interleukin 2 (IL-2) and alpha-interferon (INF-alpha). Thirty-eight patients were treated over a course of 7 weeks. Initially (day 1 + 2) patients received s.c. IL-2 at 18 x 10(6) IU m-2. During the following 6 weeks, patients received s.c. IL-2 at 3.6 x 10(6) IU m-2 for 5 days per week and s.c. INF-alpha at 5 x 10(6) for 3 days per week. Thirty eight patients were evaluated for response. An objective response was seen in seven patients (18.4 +/- 12.3%), with one complete response and six partial responses. Median duration of response was 6.7 months. Toxicity could be evaluated in 38 patients and was limited. Mild to moderate toxicity included fever (97%), fatigue or malaise (76%), nausea or vomiting (50%), anorexia (32%), hypotension (26%), neurological disturbances (26%) and hypercreatininaemia (39%). In addition, four grade IV haematological toxicities were noted. No cardiac side effects were seen. IL-2 and INF-alpha given by this schedule can be safely administered in an outpatient setting. The objective response rate was similar to our previous treatments with high-dose IL-2 given as a continuous infusion. PMID- 8198981 TI - In vivo cytokine production and recombinant interleukin 2 immunotherapy: an insight into the possible mechanisms underlying clinical responses. AB - Recombinant interleukin 2 (rIL-2), when given to patients with advanced malignant disease, induces a limited beneficial effect, with only 20-30% of patients with solid tumours responding. This present study has identified those patients with advanced colorectal cancer most likely to respond to rIL-2 therapy, by analysis of serum cytokine levels, prior to and during rIL-2 treatment, documented in responders and non-responders. Responders were found to have significantly lower pretreatment serum IL-6 and soluble IL-2 receptor levels (sIL-2R) than non responders (P < 0.01 and P < 0.05 respectively). During rIL-2 infusion, responders developed high circulating levels of IL-6 and had low constant levels of prostaglandin E2 (PGE2). Non-responders failed to produce IL-6 and demonstrated elevated serum concentrations of PGE2, during infusions of rIL-2. Thus, an enhanced ongoing IL-6 and sIL-2R response, prior to therapy, was detrimental to subsequent treatment with rIL-2. Differential production and/or release of cytokines and prostaglandins, during therapy, further determined the likelihood of response to rIL-2. PMID- 8198982 TI - Phase II study of nitrosourea fotemustine as single-drug chemotherapy in poor prognosis non-small-cell lung cancer. AB - A phase II study was designed to evaluate objective response rate and toxicity of fotemustine as single-drug chemotherapy in non-small-cell lung cancer. Eighty seven patients with unresectable non-small-cell lung cancer took part in the study. Seventy-seven were evaluable for response. Of these, 60% had received prior chemotherapy and 74% had metastatic disease. Moreover, 22 patients had central nervous system metastases (of whom 12 were evaluable for this site). Treatment consisted of fotemustine 100 mg m-2 administered on days 1 and 8 followed by a 5 week rest period. Afterwards, responding or stabilised patients received fotemustine 100 mg m-2 every 3 weeks as a maintenance therapy. Toxicity and quality of life were recorded during therapy. Thirteen patients (17%; 95% CI 9-25%) had an objective response (11% for pretreated, 26% for non-pretreated) with a median duration of 22 weeks (range 7-41 weeks). Two objective responses were observed among the 12 patients with evaluable brain metastases. No response was observed among the 14 patients with adenocarcinoma. Haematological, gastrointestinal, hepatic and renal toxicities were mild to moderate and manageable. The most frequent biological adverse reactions were delayed thrombocytopenia and neutropenia. Quality of life did not significantly decrease during the first 6 treatment weeks. Moreover, it remained stable during the study period in patients with response or stabilisation, whereas it significantly decreased in patients who experienced progression of the disease. Fotemustine is feasible for single-drug chemotherapy in non-small-cell lung cancer even though poor prognostic variables such as brain metastases are present. It can be administered on an outpatient basis and toxicity is moderate and manageable. Thus, fotemustine can be considered as a putative drug in further combinations. PMID- 8198983 TI - Selective venous sampling catheterisation for localisation of persisting medullary thyroid carcinoma. AB - Selective venous sampling catheterisation was performed in 19 patients with medullary thyroid carcinoma without known distant metastases for persistent hypercalcitoninaemia after surgery. Calcitonin (CT) gradients were found in the neck and/or the mediastinum in 18 patients and in five patients at distant sites also. After venous catheterisation, 13 patients were subjected to repeat surgery. Neck and/or mediastinal tumour foci were found in 12 patients at the sites of the CT gradients. Of these, nine patients had only cervicomediastinal CT gradients: after reoperation, the serum CT level normalised in one, significantly decreased in five, and did not change in three, and no neck relapse occurred after a mean follow-up of 5.3 years. Distant metastases emerged clinically in all five patients with distant gradients and in only one of the 14 patients with no distant gradient. In conclusion, selective venous catheterisation is the most sensitive tool for the localisation of residual disease and for the early detection of distant metastases. However, in patients with only local disease, biochemical cure is rarely obtained after reoperation. PMID- 8198984 TI - p53 mutations and overexpression in locally advanced breast cancers. AB - Alterations in the p53 gene were analysed in 39 patients with locally advanced breast cancers (LABCs) (stage III-IV) with inflammatory signs in most cases (UICC stage T4d = 32 patients) by molecular and immunohistochemical (IHC) approaches. All patients were included in the same therapy protocol. Using polymerase chain reaction (PCR) and a single-strand conformational polymorphism migration technique (SSCP), the presence of mutations in exons 2-11, covering the entire coding sequence of the p53 gene, was evaluated. Using the mouse specific anti human p53 monoclonal antibody (PAb 1801), we also looked for overexpression of the p53 protein in tissue sections. In 16 cases shifted bands were reproducibly identified by PCR-SSCP, and all but one (localised to exon 10) were in exons 5-8, the usual mutational hotspots. Fifteen of these 16 samples were sequenced and 14 of the suspected mutations (36%) were confirmed. Most of them (12) were single nucleotide substitutions, and transitions were more frequent (eight cases) than transversions (four cases). Fourteen of the tumour samples were positively stained with the monoclonal antibody PAb 1801, 11 with nuclear staining only, two with mixed cytoplasmic and nuclear staining and one with cytoplasmic staining only. Staining patterns were very heterogeneous in terms of the percentage of positive cells (10-75%) and their distribution in the tissue section (isolated foci or dispersed cells). In 11 of the 14 mutated cases a positive immunostaining was observed. The presence of a p53 mutation was significantly associated with larger tumour diameter (chi 2 = 7.490, P = 0.0062) and the presence of clinical metastases (stage IV) (chi 2 = 10.113, P = 0.0015). A non-statistically significant trend of association was observed between p53 mutation, negative oestrogen receptors and lower response rate to therapy. Our results in this group of patients and the heterogeneity of the staining of tumour cells in tissue sections suggest that p53 mutations could be a late event in this non-familial form of breast cancer. PMID- 8198985 TI - Phosphorus-31 metabolism of post-menopausal breast cancer studied in vivo by magnetic resonance spectroscopy. AB - We have studied the metabolism of 31P-containing metabolites of post-menopausal breast cancers in vivo using magnetic resonance spectroscopy (MRS) and a 5.5 cm surface coil. Spectra were acquired from 23 diameter. The spectra of the 19 previously untreated tumours had significantly higher phosphomonoester (PME) 31P relative peak areas than the normal breasts of eight post-menopausal women (11.7% and 7.7% respectively, P = 0.002). Although an increased PME relative peak area was characteristic of malignancy, PME relative peak area is similarly raised in lactating breast and, therefore, not a specific feature of cancer. An apparently lower nucleotide triphosphate (NTP) relative peak area in tumours than healthy postmenopausal breast was secondary to the differences in PME relative peak area; contamination by signal from chest wall muscle probably accounts for the ostensibly higher phosphocreatine (PCr) relative peak area of the tumours. Spectroscopy was repeated following chemotherapy in six women. An increase in PCr relative peak area was seen in all five patients who responded, but again this may represent increased contamination secondary to changes in tumour size. A fall in PME relative peak area was noted in four responders, but also one non responder, so this finding may not be sufficiently specific to be of use clinically. Further studies are need to elucidate fully the role of MRS in breast cancer. PMID- 8198986 TI - Overexpression of group II phospholipase A2 in human breast cancer tissues is closely associated with their malignant potency. AB - Membrane-associated phospholipase A2 (M-PLA2) is an enzyme that hydrolyses the sn 2 fatty acyl ester bond of phosphoglycerides. We measured M-PLA2 concentration in tissue extracts from 325 human breast cancers using a specific radioimmunoassay recently developed. Correlation analyses between the tissue concentration of M PLA2 and clinicopathological factors showed that the enzyme level was significantly higher in patients with distant metastasis than in those without. In addition, M-PLA2 concentration was significantly higher in scirrhous carcinoma than in other histological types. No significant association was found between M PLA2 concentration and age, menstrual status, tumour size, histological grade, vessel involvement or oestrogen receptor (ER) and progesterone receptor (PR) status. The expression of M-PLA2 mRNA was examined in a fibroadenoma, a stage IV breast cancer and its metastatic site of skin. Northern blot analysis showed a clear hybridisation band corresponding to M-PLA2 mRNA in both primary breast cancer and its metastatic site, while the fibroadenoma expressed a faint band corresponding to M-PLA2 mRNA. Breast cancer patients with high M-PLA2 concentrations exhibited significantly shorter disease-free and overall survival than those with low M-PLA2 concentration at the cut-off point of 5 ng 100 mg-1 protein, which was determined in a separate study. In multivariate analysis, M PLA2 was found to be an independent prognostic factor for disease recurrence and death in human breast cancer. The possible significance of M-PLA2 expression in human breast cancer tissue is discussed. PMID- 8198987 TI - Combined treatment with 4-hydroxyandrostenedione and aminoglutethimide: effects on aromatase inhibition and oestrogen suppression. AB - The effects of a combination of aminoglutethimide (AG) 1,000 mg daily and 4 hydroxy-androstenedione (4OHA) 500 mg i.m. weekly on peripheral aromatase activity as measured by in vivo radioisotopic tracer methodology and serum oestrogen suppression were investigated in ten post-menopausal women with advanced breast cancer. Patients were treated for a minimum of 4 weeks with 4OHA before addition of AG for a minimum of 6 weeks. Aromatase inhibition was found to be nearly identical in the two treatment situations (92.5 +/- 4.7% and 93.8 +/- 3.8% respectively). There was no further significant suppression of plasma oestradiol or plasma oestrone levels when AG was added to 4OHA treatment (mean decrease of 7.6 +/- 12.1% and 2.8 +/- 12.0% respectively). In contrast, adding AG caused a further suppression of plasma oestrone sulphate (Oe1S) compared with 4OHA monotherapy (mean suppression of 35.2 +/- 9.1%, P < 0.025). This effect on Oe1S may be due to an influence of AG on oestrogen metabolism. PMID- 8198988 TI - Differences in MHC and TAP-1 expression in cervical cancer lymph node metastases as compared with the primary tumours. AB - In previous studies we have shown down-regulation of class I major histocompatibility complex (MHC) expression in a significant proportion of primary cervical carcinomas, which was found to be strongly correlated with loss of expression of the transporter associated with antigen presentation (TAP). By contrast, class II MHC expression was frequently up-regulated on neoplastic keratinocytes in these malignancies. In order to investigate whether these changes are associated with biological behaviour of the tumours, 20 cervical carcinomas were analyzed for MHC (HLA-A, HLA-B/C, HLA-DR) and TAP-1 expression in the primary tumours and in lymph node metastases by immunohistochemistry. The results showed a significant increase in the prevalence of HLA-A and HLA-B/C down regulation in metastasised neoplastic cells as compared with the primary tumour (P = 0.01). In all cases this was accompanied by loss of TAP-1 expression. Up regulated HLA-DR expression was found exclusively in primary tumours and was absent in the corresponding metastases (P = 0.002). These data are consistent with the hypothesis that loss of TAP-1 and the consequent down-regulation of class I MHC expression provides a selective advantage for neoplastic cervical cells during metastasis. Furthermore, the lack of class II MHC expression in metastasised cells either reflects a different local lymphokine production or indicates that these cells may have escaped CD4+ cytotoxic T-lymphocyte (CTL) mediated killing. PMID- 8198989 TI - Statistical aspects of prognostic factor studies in oncology. PMID- 8198990 TI - Adjuvant 5-fluorouracil plus levamisole in colon cancer: the plot thickens? PMID- 8198991 TI - Selective toxicity of TGF-alpha-PE40 to EGFR-positive cell lines: selective protection of low EGFR-expressing cell lines by EGF. AB - The sensitivity of human breast and lung cancer cell lines to TGF-alpha-PE40, a novel chimeric recombinant cytotoxin composed of two independent domains, (i) TGF alpha and (ii) a 40 kDa segment of the Pseudomonas exotoxin protein, PE-40, was investigated. Toxicity varied widely, correlated with epidermal growth factor receptor (EGFR) levels (P = 0.01) and was greatly reduced by EGF, indicating that binding of TGF-alpha-PE40 to EGFR is important in mediating toxicity. Cell lines expressing low EGFR levels were most highly protected by EGF, indicating that normal (low EGFR-expressing) tissue may be selectively protected by EGF in vivo. P-glycoprotein did not confer resistance to TGF-alpha-PE40, and toxicity was unaffected by multidrug resistance-modulating agents (cyclosporin A, tamoxifen, verapamil), indicating a role for TGF-alpha-PE40 in the clinical management of drug-resistant tumours. PMID- 8198992 TI - Expression of ras oncogene p21 protein in normal and neoplastic laryngeal tissues: correlation with histopathological features and epidermal growth factor receptors. AB - Western blotting analysis of the p21 ras oncoprotein was performed in seven normal laryngeal mucosa specimens and 43 primary laryngeal cancers. Varying p21 levels, expressed as optical density (OD), were found in normal mucosa (median 1.94 OD, range 0.90-2.17 OD) and in primary laryngeal tumours (median 1.74 OD, range 0.30-6.37 OD). When p21 expression in laryngeal cancer was compared with the normal counterpart, higher levels were found in neoplastic than in normal laryngeal tissue (median 2.54 OD, range 1.76-6.37 OD, vs median 1.94 OD, range 0.90-2.17 OD) (P = 0.023). Immunohistochemical analysis demonstrated that most of the tumour cells (more than 70%) were immunostained while the stromal component was unreactive. No correlation between p21 expression and tumour location, stage and histopathological grade was observed. The correlation between ras p21 protein expression and epidermal growth factor receptor (EGFR) levels was also investigated. EGFR-positive cases did not show any difference in p21 expression with respect to EGFR-negative cases (median 1.52 OD, range 0.30-6.37 OD, vs median 1.84 OD, range 0.93-3.71 OD). Our findings suggest that overexpression of p21 protein is associated with a malignant phenotype in laryngeal cancer. Further studies should be undertaken to evaluate whether the assessment of p21 protein expression may have clinical significance in laryngeal cancer. PMID- 8198993 TI - The Clothier inquiry: lessons to be learned. Interview by Rosemary Rogers. PMID- 8198994 TI - Patient focused care without the upheaval. PMID- 8198995 TI - Refusing treatment. PMID- 8198996 TI - Diabetes: a practical guide to insulin injections. PMID- 8198997 TI - Infection control in low-risk environments. PMID- 8198998 TI - Spiritual care: the nurse's role. AB - This article presents part of a doctoral study which explored some spiritual aspects of nursing care. It reports how a sample of nurses perceived and reported how they gave spiritual care, and identifies possible influencing factors. The implications of these findings are discussed and suggestions for practice made. PMID- 8198999 TI - The Standard guide to communication. PMID- 8199000 TI - Model nurse. PMID- 8199001 TI - Management and leadership (continuing education credit). PMID- 8199002 TI - Guidelines on HIV testing. PMID- 8199003 TI - An ultrastructural study of the effect of treatment with atovaquone in brains of mice chronically infected with the ME49 strain of Toxoplasma gondii. AB - The morphological effects of drug treatment with atovaquone in the brains of mice chronically infected with Toxoplasma gondii was examined by light and electron microscopy. As early as 1 and 2 weeks of treatment there appeared to be fewer tissue cysts compared to untreated controls and this reduction was more significant after 4 weeks treatment. There also appeared to be a decrease in the number of inflammatory nodules and the severity of the meningitis. Ultrastructurally, the cysts of both treated and control animals were located within host cells. There was a marked increase in both the number of cysts with lysed bradyzoites and the number of degenerate bradyzoites after 4 weeks treatment. It is probable that the drug is more active against the metabolically active immature bradyzoites than the mature organisms. Drug treatment does not appear to result in rupture of tissue cysts or release of Toxoplasma antigens since there is a reduction rather than an increase in the inflammatory response. This drug may be useful in treating chronic toxoplasmosis since it appears to be active against the bradyzoites reducing the parasite burden (cyst number) without initiating a destructive inflammatory response. PMID- 8199004 TI - Increase of cross(auto)-reactive antibodies after immunization in aged mice: a cellular and molecular study. AB - Aging in both humans and laboratory animals is often accompanied by an increase in autoreactive antibodies. Here we report that immunization with a bacterial antigen determined a marked increase of cross-reactive antibodies in aged but not in young mice. This phenomenon was observed in the aged individuals of two different mouse strains (Balb/c and C57BL/6) after a single injection of lyophilized vaccine from Streptococcus pneumoniae R36a (Pn) that express the immunodominant epitope phosphorylcholine (PC). These data were then confirmed by the analysis of cross-reactivity of anti-PC monoclonal antibody (mAb) generated from Pn-immunized young and aged Balb/c and C57BL/6 mice. Most of the anti-PC mAb from aged mice showed a broad spectrum of cross-reactivity with a panel of self and non-self antigens, while none of the mAb from young mice did so. We also showed that a genetic shift, in the VH/VL gene repertoire of anti-PC antibody, appeared to take place in aged mice and that aged mAb displayed a decrease in antibody affinity for the free hapten PC as compared to the young ones. We interpret these data as showing that immunization at advanced age may be linked to the production of cross-reactive antibodies and that this event may be related to the increased incidence of autoantibody in the aged. PMID- 8199005 TI - Fat-storing cells and myofibroblasts are involved in the initial phase of carbon tetrachloride-induced hepatic fibrosis in BN/BiRij rats. AB - This study on the appearance, distribution and kinetics of fibroblast-like cells (fat-storing cells, transitional cells, myofibroblasts and fibroblasts) after CCl4-treatment was undertaken to delineate further the respective roles of these cell types in liver fibrogenesis. The different cell types were distinguished on the basis of their immunophenotypic pattern with a combination of marker antibodies and on the basis of ultrastructural characteristics. Combined staining for alpha-smooth muscle actin (sma) and desmin (Des) revealed perisinusoidal fat storing cells (FSC) as d+ sma- and myofibroblasts around the central veins of the normal rat liver as d+ sma+. During the initial phase of CCl4-induced hepatic fibrosis (week 1 and 2), the number of d+ sma+ cells increased in the degenerating area around the central veins and d+ sma+ cells appeared in the very thin fibrotic septa at week 2. Ultrastructural examination of the affected central areas showed the presence of myofibroblasts. These sma+ cells proliferated, as shown by double staining for bromodeoxyuridine (BrdU) and sma. In degenerating parenchymal areas, d+ sma- FSC were present. The FSC in the perisinusoidal space of areas which were not affected by CCl4 intoxification, remained d+ sma-. These immunostaining findings support the electron microscopical results, which show the presence of cells with the typical ultrastructural characteristics of FSC in both the degenerating areas and the perisinusoidal space of unaffected areas. After one week of CCl4-treatment, enhanced deposition of procollagen type III was observed around the central veins. Enhanced deposition of collagen type IV was seen subendothelially along the sinusoids, notably in degenerating parenchymal areas where the septa were later formed. FSC appear to be the principal source of collagen type IV during fibrogenesis. These observations further support and specify the role of FSC in early fibrogenesis. With the progression of the CCl4-induced fibrosis, d+ sma+ myofibroblasts remained localized in the fibrotic septa, but now along their outer edge. The majority of the cells in the septa were formed by d- sma- cells indicating a prominent role of fibroblasts in the septal formation. Septal fibroblasts are not only likely to produce matrix components, but also were shown to degrade collagen, as evidenced by the increased number of collagen-containing vacuoles during the course of fibrosis. In conclusion, myofibroblasts and FSC appear to be the main cell types involved in the initial phase of liver fibrogenesis induced by CCl4. Both myofibroblasts and FSC divide and transform.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8199006 TI - The clinical virology of hepatitis C virus. PMID- 8199007 TI - The pathogenesis of alcoholic liver disease. PMID- 8199008 TI - Distribution of type IV collagen in pancreatic adenocarcinoma and chronic pancreatitis. AB - Changes in the basement membrane are present in various neoplastic conditions such as neurofibrosarcoma, cervical carcinoma, colorectal cancers and hepatoblastoma. This study examines the expression of type IV collagen in the basement membrane, using an immunohistochemical method, in the normal pancreas (n = 10), chronic pancreatitis (n = 15) and pancreatic adenocarcinoma (n = 30). The formalin fixed, paraffin embedded tissue was sectioned and pretreated with protease prior to immunostaining for type IV collagen. There was a statistically significant difference in type IV collagen expression between pancreatic carcinoma and chronic pancreatitis (P = 0.0001; chi 2 test with continuity correction). In pancreatic adenocarcinoma, type IV collagen distribution in the basement membrane was discontinuous and irregular or absent around individual or groups of neoplastic cells (n = 30). Most cases of chronic pancreatitis showed continuous pattern of basement membrane type IV collagen around residual ducts (n = 10). In the normal pancreas, only one of the ten cases showed discontinuous basement membrane around pancreatic ducts, while in the rest of the cases, the pattern was continuous. This study suggests that there is abnormal distribution of type IV collagen in the basement membrane in pancreatic carcinoma, which may be related to either abnormal deposition or degradation of the collagen. Immunostaining for type IV collagen may be of some diagnostic use for distinguishing pancreatic adenocarcinoma from problematic cases of chronic pancreatitis. PMID- 8199009 TI - Pulmonary inflammation induced by repeated inhalations of beta(1,3)-D-glucan and endotoxin. AB - In an animal model of hypersensitivity pneumonitis (HP) guinea-pigs were exposed for 5 weeks to an aerosol of bacterial endotoxin, beta(1,3)-D-glucan (curdlan) or a combination. Exposure to endotoxin or curdlan showed only small changes in inflammatory cells in airways or the lung wall, histologically or in terms of enzyme secretion from alveolar macrophages. When the two agents were given together, a histology resembling HP was seen with alveolar infiltrates and early granulomas. Inflammatory cells in airways were increased and enzyme production of macrophages was changed, suggesting an effect of curdlan on the inflammatory regulating capacity of airway macrophages. The results suggest that interference with macrophage function and inflammation are important components in the development of HP. PMID- 8199010 TI - Intracellular location of Mycoplasma genitalium in cultured Vero cells as demonstrated by electron microscopy. AB - The original two strains of Mycoplasma genitalium were isolated from the human urogenital tract. No other strains have been isolated from this site since then. We have recently succeeded in propagating a third strain from a urogenital specimen from a patient with urethritis in Vero cell cultures. By electron microscopy mycoplasmas were demonstrated intracellularly in about 10% of the examined Vero cells. Various stages of penetration into the cells could be observed. The flask-shaped organisms seemed to penetrate into the cells by the tip-end which included a rodlike structure. The intracellular location of normal mycoplasmas were in membrane-bound vacuoles very close to the nucleus, occasionally together with a few disintegrated organisms. In a few cells additional material was entangling the mycoplasmas in the cytoplasmic vacuoles. The potential for intracellular survival of M. genitalium may help the organism to evade the defence mechanisms of the human body. This trait may be considered a pathogenic property which supports the presumption that M. genitalium has clinical importance. PMID- 8199011 TI - Characterization of a murine model of myocarditis induced by a reactivated coxsackievirus B3. AB - A transfection-reactivated Coxsackievirus B3 (rCVB3), from a full-length cDNA clone of Nancy strain, has previously been shown to be as cardiovirulent as the wild-type virus. Myocarditis induced by this genetically defined virus was compared in SWR mice with the traditional Balb/c model. SWR mice inoculated with rCVB3 developed more severe myocarditis but less severe pancreatitis than Balb/c mice. In contrast to the poor general health and frequent mortality of Balb/c mice following CVB3 infection, the body weight of SWR mice was not affected by CVB3 inoculation and no mortality occurred at titres of 10(2)-10(7) plaque forming units (PFU). Typical myocarditis developed in SWR mice 7 days post infection. Myocarditic foci consisting of necrotic myocardial fibres and mononuclear cell infiltrates resolved by day 30, similar to that observed in Balb/c. However, SWR mice were more sensitive to rCVB3-induced myocarditis than were Balb/c mice: mild myocarditis was induced (4/4) by as low as 10(2) PFU of the virus (ID50 < 10(1.5) PFU), and more severe myocarditis was seen at higher PFU of virus in a dose-dependent manner. The SWR model was tested with attenuated variants derived from cardiovirulent rCVB3. The ID50 for myocarditis was 10(7) PFU for a large plaque-size attenuant and 10(6) PFU for a minute plaque-size attenuant, indicating loss of cardiovirulence by a factor of more than 10(4) 10(5). rCVB3-induced SWR mouse is a sensitive and reliable model for myocarditis. It is useful in assessing the cardiovirulence of different CVB3 variants and evaluating the efficacies of anti-viral therapies. It will allow follow-up study after high dose infection with cardiovirulent rCVB3. PMID- 8199012 TI - Physiology and function of the haemopoietic microenvironment. PMID- 8199013 TI - Characterization of specific functional receptors for HuIFN-alpha on a human megakaryocytic cell line (Dami): expression related to differentiation. AB - Interferon-alpha (IFN-alpha) treatment has been shown to be highly effective in inhibiting human megakaryocytopoiesis and controlling thrombocytosis in patients with myeloproliferative disorders. These observations suggest that IFN-alpha might play some role in the biological feature of the megakaryocytic lineage and led us to investigate the presence of specific receptors for IFN-alpha on human megakaryocytic cells, i.e. the Dami cell line, and to study the regulation of their expression. Our study demonstrates that [125I]-recombinant human IFN-alpha ([125I]rHu-IFN-alpha) binds to high-affinity specific receptor on these cells. Scatchard analysis of binding data indicates the presence of homogeneous binding sites estimated in the range of 3000-5000, with an apparent equilibrium dissociation constant, Kd, of 1-2 x 10(-9) M. Also, [125I]rHuIFN-alpha binding capacity decreased in Dami cells incubated with unlabelled rHuIFN-alpha. This down-regulation which was dose-dependent appeared to result from a reduction of IFN-alpha cell surface receptors and was observed at doses that elicited antiproliferative effects in Dami cells. Cross-linking of [125I]rHuIFN-alpha to Dami membrane proteins using a bifunctional reagent yielded to a radioactive complex of approximately 150,000 kD on SDS-PAGE. Furthermore, in response to PMA, which induces the differentiation/maturation of the Dami cells as evaluated by surface marker and ploidy analysis, a 3-fold increase of the number of specific membrane receptors for IFN-alpha was observed, without any modification of either the affinity or the M(r) value of the cross-linked complex. Such an increase appeared to be restricted to IFN-alpha receptors; actually it was not observed in [125I]IFN-gamma binding experiments. Transcript analysis indicated that down regulation and increased expression of the IFN-alpha receptor after PMA treatment are post-transcriptional events. PMID- 8199014 TI - Differential regulation of M-CSF and IL-6 gene expression in monocytic cells. AB - Using the human monocytic cell line Mono Mac 6 we studied the involvement of Ca2+, protein kinase A (PKA), and protein kinase C (PKC) dependent pathways in the regulation of M-CSF and IL-6 gene expression. The results demonstrate that on activation with the calcium ionophore A23187 both M-CSF and IL-6 mRNA are induced after 3 and 6 h respectively. Co-stimulation with A23187 plus PMA resulted in an up-regulation of M-CSF mRNA and a down-regulation of IL-6 mRNA. Conversely co stimulation with A23187 plus DBcAMP resulted in a down-regulation of M-CSF mRNA and an up-regulation of IL-6 mRNA. Nuclear run-on and mRNA half-life studies showed that the effects on the M-CSF expression were related to changes at transcriptional and post-transcriptional level. In contrast, the effects on the IL-6 gene expression seems to be mediated at post-transcriptional level. With regard to the secretion of the IL-6 protein it was shown that it closely follows the accumulation of IL-6 mRNA. Taken together, the data show that several intracellular signalling pathways control strictly the cytokine expression in monocytic cells which gives the cells the opportunity to respond variably to external activation signals. PMID- 8199015 TI - The acute lymphoblastic leukaemia cell line SEM with t(4;11) chromosomal rearrangement is biphenotypic and responsive to interleukin-7. AB - A cell line, designated SEM, was established from the peripheral blood of a 5 year-old girl in relapse with acute lymphoblastic leukaemia (ALL). Both the lymphoblasts of the patient and the cells of the cell line SEM showed the t(4;11) chromosomal rearrangement. The analysis of the immunophenotype of the SEM cell line revealed the B-cell differentiation antigens CD19, CD22 and CDw75 in the absence of CD20, CD24 and immunoglobulin expression. Besides B-lineage antigens, SEM cells were positive for the myeloid antigens CD13, CD15, CD33 and CDw65. Immunogenotypic analysis of SEM cells showed a monoclonal rearrangement of immunoglobulin heavy-chain (IgH). T-cell receptor (TCR) gamma and delta genes. Addition of interleukin (IL)-7 promoted the growth of the patient's lymphoblasts in culture and enhanced the proliferation of SEM cells. The SEM cells also express messenger RNA (mRNA) for the IL-7 receptor (IL-7R), but no evidence for autocrine production of IL-7 by the cell line was found. Addition of IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-alpha, or IFN-gamma resulted in a profound inhibition of SEM growth. Thus, these cytokines may have important growth regulatory activities for biphenotypic leukaemic ALL cells. PMID- 8199016 TI - Improved survival for acute lymphoblastic leukaemia in infancy: the experience of EORTC-Childhood Leukaemia Cooperative Group. AB - Out of 744 newly diagnosed ALL children under the age of 18 years treated according to the EORTC-CLCG protocols 58831 and 58832, 28 (4%) were infants less than 1 year of age. An elevated risk factor, which takes into account the sizes of the liver and spleen and the number of circulating blasts, was present in 25 cases. Most patients had non-common ALL. Among 15 patients studied by cytogenetics, nine present chromosomal abnormalities, six of them having a t(4;11) translocation. Complete remission was achieved in 86% of cases. One patient died in complete remission of therapy-related infection. The overall EFS is 43%. It is not statistically different in very young infants as compared to infants older than 6 months. Except for patients with AUL or with t(4;11) translocation, a continuous complete remission rate above 50% can be achieved with a median follow-up of 4 years. The results obtained in infant ALL with EORTC CLCG protocols are currently better than those obtained with some other protocols, but remains inferior when compared to the ones obtained in older children. Thus, further improvements are needed and should be evaluated in large cooperative trials. PMID- 8199017 TI - T-cell receptor beta gene rearrangements in leukaemic B-cells from patients with chronic lymphocytic leukaemia: association with chromosome 6 deletions. AB - Rearrangement of immunoglobulin genes is a characteristic finding in normal B cells and in leukaemic cells of B-cell origin. In some leukaemic cells simultaneous cross-lineage rearrangement of immunoglobulin- and T-cell receptor (TcR) genes occur. We have analysed TcR beta gene rearrangement in 100 patients with B-cell chronic lymphocytic leukaemia. All samples expressed CD5, CD19 and CD20 and six patients had rearrangements of both immunoglobulin and TcR beta genes. Analysis of gene expression in cells with TcR beta gene rearrangement indicated production of truncated TcR beta transcripts but no expression of the T cell markers CD3, CD4, CD8, TcR alpha beta or delta on the cell surface. Three of the patients with both Ig and TcR beta rearrangement (50%) were 44 years or younger at diagnosis and cells from three such patients expressed IgG. Three of the six patients had a terminal deletion of the long arm of chromosome 6 with different breakpoints, with or without other chromosomal abnormalities, whereas 6q deletions were found in 4/94 patients without TcR beta gene rearrangement (4.3%) (P = 0.001). This study indicates a correlation between TcR beta gene rearrangement and deletion of chromosome 6q. PMID- 8199018 TI - Persistence of an activating N-RAS oncogene mutation in clonogenic progenitor cells from an acute myeloid leukaemia patient in remission. AB - A patient with acute myeloid leukaemia (AML) with an activating N-RAS oncogene mutation was studied in a haemopoietic clonogenic progenitor cell assay. Individual colonies and clusters were analysed by polymerase chain reaction and oligonucleotide hybridization for the original mutation. The mutation was detected in a majority of leukaemic clusters, but also in almost half of the differentiated colonies. After chemotherapy the patient entered clinical remission. However, the mutation could still be detected in the bone marrow. Only differentiated colonies and no leukaemic clusters were grown from the remission bone marrow, but the original mutation was still detectable in almost half of the colonies. PMID- 8199019 TI - Platelet-derived growth factor expression in accelerated and blastic phase of chronic myelogenous leukaemia with myelofibrosis. AB - Myelofibrosis is sometimes associated with accelerated and blastic phase of chronic myelogenous leukaemia (CML). In order to investigate the role of platelet derived growth factor (PDGF) in this pathogenesis, expression and production of PDGF was studied in the blast cells from 11 patients. Five patients had myelofibrosis with myeloid blasts, while six patients did not show fibrosis, including three with myeloid blasts and three with lymphoid blasts. PDGF-A chain transcript was expressed in most of the patients. On the other hand, PDGF-B chain transcript was detected in all of the five patients with myeloid blasts and with fibrosis, in one of the three patients with myeloid blasts and without fibrosis, and in none of the three lymphoid crisis patients without fibrosis. In the patients with myeloid blasts and with fibrosis, PDGF protein, PDGF-AB and/or PDGF BB, was found to be secreted from blast cells. In addition, the PDGF activity in the culture of myeloid blasts from two patients with fibrosis was also growth stimulatory for human marrow fibroblasts. These results suggest that expression and secretion of PDGF-AB or PDGF-BB in blast cells play an important role in the pathogenesis of marrow fibrosis associated with accelerated and blastic phase of CML. PMID- 8199020 TI - Detection of clonal T-cell populations in gastrointestinal lymphomas by analysis of cRNA conformational polymorphisms of rearranged T-cell-receptor-gamma genes. AB - Analysis of complementary RNA molecules of junctional regions of rearranged T cell-receptor-gamma genes show a pattern of conformational polymorphisms which is specific for an individual lymphocytic clone. In a blinded study we analysed formalin-fixed, paraffin-embedded histological specimens from gastrointestinal lymphomas and control tissues (lymphomas: pleomorphic T-cell 10, anaplastic large cell [Ki1+] 9, centroblastic 5, immunocytoma 1, B-CLL 2, Hodgkin's 2, centroblastic-centrocytic 1, MALT [mucosa associated lymphoid tissue] 1, T-cell acute lymphoblastic leukaemia 1, non-lymphoid or polyclonal lymphoid tissues 5). Junctional regions of rearranged TCR-gamma genes were amplified by the polymerase chain reaction and the products were transcribed into cRNA. Conformational patterns of cRNA molecules were analysed by polyacrylamide gel electrophoresis. 13/20 T-lineage lymphomas and the T-cell acute lymphocytic leukaemia displayed a distinct cRNA band pattern, all B-lineage lymphomas and the non-lymphoid control tissues were negative. Only one case of nasopharyngeal (lymphoepithelial, Schmincke-Regaud) carcinoma showed a faint cRNA banding pattern. This novel and non-radioactive assay allows for the rapid detection and molecular characterization of clonal lymphoid populations in minute histological biopsy specimens. PMID- 8199021 TI - Fibrin degradation product D-dimer induces the synthesis and release of biologically active IL-1 beta, IL-6 and plasminogen activator inhibitors from monocytes in vitro. AB - Disseminated intravascular coagulation, characterized by circulating fibrin(ogen) degradation products (FDP), is associated with both acute and chronic inflammatory conditions. Since the association of FDP with monocytes could influence the release of cytokines and other regulatory proteins with significant clinical ramifications, we have studied cytokine synthesis and release following the interaction of D-dimer (DD), a terminal degradation product of fibrin, with human monocytes in vitro. Adherent peripheral blood monocytes were incubated with purified DD for 24 and 48 h and secreted or cell-associated IL-1 beta and IL-6 antigen levels and activity determined. DD (50 micrograms/ml) boosted the secretion of IL-1 beta antigen from median control levels of 659 pg/ml to 2704 pg/ml and that of IL-6 antigen from 806 pg/ml to > 3000 pg/ml at 48 h (P < 0.05). Similar increases in extracellular biologically active IL-1 and IL-6 were observed. Although DD increased cell associated IL-1 beta antigen levels from median values of 188 to 1600 pg/106 cells and IL-6 antigen from 660 to 2215 pg/106 cells (P < 0.05), cell-associated IL-1 functional activity decreased from control levels of 98 inhibitor units/ml to 65 units/ml for cells exposed to DD. Secreted plasminogen activator inhibitor (PAI) bioactivity and PAI type 2 antigen levels were significantly increased following exposure of monocytes to DD. This may explain the decreased cell associated IL-1 activity observed in our study as PAI are known to inhibit biologically active membrane bound IL-1. Our finding that DD enhances monocyte release of biologically active cytokines suggests the presence of positive feedback pathways for fibrinogen synthesis by hepatocytes. Furthermore, the association of monocytes with DD may potentiate localized coagulation processes by subsequent alterations in pericellular proteolysis. PMID- 8199022 TI - The role of platelet von Willebrand factor in platelet adhesion and thrombus formation: a study of 34 patients with various subtypes of type I von Willebrand disease. AB - In order to investigate the respective role of plasma and platelet von Willebrand factor (vWF) in mediating platelet adhesion and thrombus formation, we performed ex vivo perfusion studies with native blood from patients with various subtypes of type I von Willebrand disease (vWD). We studied 34 patients with type I vWD (19 'platelet normal', five 'platelet low', two 'platelet discordant', eight 'Vicenza'). Parallel studies were carried out on nine patients with severe vWD (type III). At high shear rate (2600 s-1) we found that the defect in platelet vessel wall interactions in patients having a normal platelet vWF content ('platelet normal' and 'Vicenza') involved thrombus formation, whereas platelet adhesion was normal. At this high shear rate, platelet adhesion and thrombus volume were significantly decreased in patients with subtypes 'platelet low' and 'platelet discordant', i.e. when platelet vWF is either low or dysfunctional. These results indicate that platelet vWF may substitute for plasma vWF to promote platelet adhesion, emphasizing the important role of platelet vWF. They also confirm the role of vWF in thrombus formation at high shear rate because an abnormal thrombus volume was observed in all patients, even when platelet adhesion was normal. PMID- 8199023 TI - Patients with severe von Willebrand disease are insensitive to the releasing effect of DDAVP: evidence that the DDAVP-induced increase in plasma factor VIII is not secondary to the increase in plasma von Willebrand factor. AB - It is generally held that factor VIII (FVIII) does not increase in the plasma of severe von Willebrand disease (vWD) patients treated with DDAVP because they lack von Willebrand factor (vWF), which is the plasma carrier for FVIII. To test this hypothesis, FVIII plasma levels were monitored in severe vWD patients treated with DDAVP after normalization of vWF plasma levels with infusions of cryoprecipitate. Each of four severe vWD patients underwent four different treatments at intervals of at least 15 d: (1) cryoprecipitate plus DDAVP; (2) cryoprecipitate plus saline; (3) cryoprecipitate plus recombinant FVIII (rFVIII); (4) saline plus rFVIII. Cryoprecipitate increased the plasma levels of FVIII and vWF. The infusions of saline or DDAVP after cryoprecipitate did not further increase FVIII and vWF plasma levels and had no effect on the plasma levels of tissue plasminogen activator (tPA), which are raised by DDAVP in normal subjects and in patients with vWD of other types. The infusion of rFVIII further increased by 182 +/- 32 U/dl (mean +/- SEM) the plasma levels attained after cryoprecipitate, which disappeared from the circulation with a half-life of 11.95 +/- 0.86 h. In contrast, the infusion of rFVIII after saline increased by only 107 +/- 18 U/dl the plasma levels of FVIII, which disappeared from the circulation with a half-life of 2.68 +/- 0.14 h, indicating that the vWF infused with cryoprecipitate is able to bind additional FVIII. These studies indicate that DDAVP does not increase the plasma levels of FVIII in patients with severe vWD even after normalization of plasma vWF. The possibility is discussed that severe vWD patients may be insensitive to the releasing effect of DDAVP. PMID- 8199025 TI - The contribution of the haematocrit to thrombocytopenic bleeding in experimental animals. AB - Clinical studies in anaemic uraemic patients have shown that increasing the haematocrit with either red blood cell (RBC) transfusions or erythropoietin corrects the prolonged bleeding time (BT) often seen in such individuals. In this present study we evaluated experimentally the effect of the haematocrit on the BT using a microvascular BT technique in New Zealand White rabbits. The correlation between haematocrit and BT was studied in both normal and thrombocytopenic rabbits. In non-thrombocytopenic animals the microvascular BT varied inversely with the haematocrit (r = -0.799); animals with haematocrit levels above 35% having significantly shorter BTs than animals with haematocrit values lower than 35% (P < 0.001). To assess the role of the haematocrit on the BT in thrombocytopenic animals, thrombocytopenia was induced by a combination of gamma irradiation and heterologous platelet antiserum. Such experiments showed that anaemic rabbits had significantly longer BTs than non-anaemic animals with a similar degree of thrombocytopenia (P = 0.0001). These data thus provide evidence that anaemia contributes significantly to the prolonged BT in both thrombocytopenic and non-thrombocytopenic rabbits, and that RBC transfusions are capable of shortening the BT in thrombocytopenic anaemic animals. While results obtained from animal models cannot necessarily be extrapolated to the clinical situation, the fact that haematocrit influences the BT must be taken into account in the assessment of anaemic patients, particularly those who may have an associated haemostatic disorder. PMID- 8199024 TI - Abnormal cAMP-induced phosphorylation of rap 1 protein in grey platelet syndrome platelets. AB - We previously demonstrated abnormal Ca2+ transport by microsomes in platelets from a grey platelet syndrome patient. Here, we investigated the platelet Ca2+ ATPases that mediate this transport, as well as its possible regulation by rap 1 protein. We showed that grey platelet syndrome platelets expressed the same two distinct Ca2+ ATPases as those recently described in normal platelets; the 100 kD SERCA2-b isoform (Sarco/Endoplasmic Reticulum Ca2+ATPase) and a new 97 kD SERCA isoform. The two Ca2+ATPases formed similar amounts of transient phosphorylated intermediates. The expression of these two Ca2+ATPases was compared by Western blotting using specific antibodies, which again emerged in similar amounts in normal and grey platelet syndrome platelets. As regards the protein phosphorylated by cAMP, it was found to be identical to rap 1 protein when it was immunoprecipitated with an antibody raised against a synthetic peptide specific for rap 1 protein. Although the expression of rap 1 protein was similar in membranes isolated from grey platelet syndrome and normal platelets, its exogenous phosphorylation by cAMP was abnormal, with a concentration (10 micrograms/ml) of the catalytic subunits of the cAMP-dependent protein kinase (C.Sub.), as it decreased to half the control level. It is concluded that the abnormal Ca2+ transport found in grey platelet syndrome platelets is not due to the abnormal expression of the Ca2+ATPases, but is associated with an abnormality of rap 1 protein phosphorylation by cAMP. PMID- 8199026 TI - Characterization of haemolyser-resistant cells increased in the blood of erythropoietin-treated mice. AB - Recently, we reported a new in vivo assay method for erythropoietin (Epo) by means of counts of the number of haemolyser-resistant cells (HRCs) increased in Epo-injected mice. Here, we attempted to characterize the HRCs. Flow-cytometric studies revealed that HRCs obtained from Epo-injected mice expressed the transferrin receptor on their surface membranes. Furthermore, a fluorophotometric study suggested that the number of transferrin receptor-positive cells increased in a dose-dependent manner in response to treatment with Epo. On the other hand, flowcytometric and fluorophotometric studies of glycophorin A on HRCs using a rabbit antiglycophorin A antibody also showed a high expression of glycophorin A on them as compared with on HRCs from vehicle-treated animals (control). The results indicated that HRCs could be defined by their expression of both transferrin receptors and glycophorin A. We concluded that HRCs might be immature reticulocytes. PMID- 8199027 TI - The molecular basis of beta thalassaemia in Punjabi and Maharashtran Indians includes a multilocus aetiology involving triplicated alpha-globin loci. AB - We have analysed 201 beta-thalassaemia (beta-thal) genes from natives of the Punjab (156) and Maharashtra states of India and found the causative mutation in 200 of them. The most common beta-globin gene mutations differed significantly between these two groups and between these groups and Indian immigrants in the U.S.A. and the U.K. In the Punjabi Indians the IVS-1, nt 1 (G-T) mutation accounted for nearly one-quarter of beta-thal genes, whereas it was 5% or less in the other groups. Likewise, the cap + 1 mutation was much more prevalent in the Punjabis, whereas the nonsense codon 15 allele had a higher frequency in the Maharashtrans of the Bombay region. The common IVS-1, nt5 allele had a frequency of 60% of beta-thal genes in the Maharastrans, 35% in North American immigrants, and only 23% in the Punjabis. Two-thirds of all beta-thal genes in Punjab were found in the merchant caste (Khatri-Arora), whereas the menial caste (Shudra) was highly represented among those with beta-thal genes in Maharashtra. Two novel beta-globin alleles were each found once; a frameshift codon 55 (+A) in Maharashtrans and a frameshift codons 47-48 (+ATCT) in Punjabis. Of three Punjabi patients with beta-thal intermedia in whom only a single severe beta-globin gene mutation was found, two had six alpha-globin genes (homozygosity for a triplicated alpha-globin locus) instead of the normal alpha-globin gene number of four. Thus, these two individuals had a multilocus aetiology of beta-thal and their parents have the unusual recurrence risk of 1 in 8 for conceiving a third with beta-thal intermedia. Since 15% of 126 alpha-globin clusters studies in Punjabis contained either single (10%) or triplicated (5%) alpha-globin genes, the alpha-globin gene number is a frequent modifier of the phenotype of beta-thal in this ethnic group. PMID- 8199028 TI - Severe thalassaemia intermedia caused by interaction of homozygosity for alpha globin gene triplication with heterozygosity for beta zero-thalassaemia. AB - A 3-year-old child was evaluated for beta-thalassaemia intermedia. Molecular characterization including beta-globin gene sequence analysis revealed heterozygosity for a single beta-thalassaemia mutation, IVSI nt1 (G-->A). In addition the patient was found to be homozygous for alpha-globin gene triplication (alpha alpha alpha anti3.7/alpha alpha alpah anti3.7). The propositus has a significantly more severe phenotype than has been previously reported with this combination of genetic defects. In contrast, four individuals heterozygous for both triplicated alpha and for beta thalassaemia had a phenotype of thalassaemia minor, and a fifth had very mild thalassaemia intermedia. PMID- 8199029 TI - Plasma soluble interleukin-2 receptor in patients with primary myelofibrosis. AB - Using en enzyme-linked immunosorbent assay (ELISA) test, the level of soluble Tac peptide, one chain of the human interleukin-2 receptor, was measured in the plasma of 26 patients with primary myelofibrosis (MF), seven patients with polycythaemia vera and 11 normal controls. The plasma soluble interleukin-2 receptor (sIL-2R) was found to be significantly elevated in patients with primary MF compared to polycythaemia vera or controls (P < 0.001), while the plasma sIL 2R of patients with polycythaemia vera also was found to be significantly elevated compared to controls (P < 0.01). The significantly elevated value of sIL 2R seen in primary MF may be secondary to T cell activation resulting from autoimmune phenomena, and myeloblast activation with release of sIL-2R may also be a contributing factor. In primary MF, plasma sIL-2R levels were also found to be correlated to survival, circulating blast cell counts, and thrombocytopenia, but not to white blood cell counts, LDH levels, degree of marrow fibrosis, or degree of splenomegaly. Patients with primary MF with higher titre of plasma sIL 2R had a shorter survival. Further studies involving more patients and longer follow-up may substantiate that plasma sIL-2R is an important prognostic indicator in primary MF. PMID- 8199030 TI - Adult T-cell leukaemia/lymphoma featuring a large granular lymphocyte leukaemia morphologically. AB - A 70-year-old man from an endemic area of human T-cell lymphotropic virus type I (HTLV-I) developed rapid generalized lymphadenopathy and abdominal tumours. The white blood cell count was 198.3 x 10(9)/l with 93% lymphocytes, 66.3% of which expressed large granular lymphocytes (LGLs). Bone marrow and lymph nodes were also infiltrated by LGLs. Surface markers were positive for CD4, CD25 and HLA-DR, and negative for CD3, CD8, CD16, CD56 and CD57. A monoclonal integration of HTLV I proviral DNA was demonstrated on these LGLs by Southern blot hybridization analysis. This fact indicates that some adult T-cell leukaemia/lymphoma may morphologically present LGL leukaemia. PMID- 8199031 TI - Interleukin-1 alpha as an autocrine growth factor for acute lymphoblastic leukaemia cells. AB - We describe a case of B-lineage acute lymphoblastic leukaemia (ALL) with proliferation of leukaemic cells through an interleukin-1 alpha (IL-1 alpha) autocrine mechanism. Flow cytometric analysis using the IL-1 receptor type II (IL 1Rt II) monoclonal antibody (mAb) demonstrated the expression of the IL-1Rt II on leukaemic cells: this is the first report in IL-1RtII-positive freshly isolated ALL cells from a patient. In accordance with the expression of IL-1RtII, the leukaemic cells proliferated in response to exogenous IL-1 alpha. In addition, anti-IL-1 alpha mAb markedly inhibited the spontaneous cell proliferation. Furthermore, Northern blot analysis detected IL-1 alpha mRNA without any stimulation. These observations suggest that IL-1 alpha may play an important role as an autocrine growth factor in some cases of ALL. PMID- 8199032 TI - A case of POEMS syndrome with thrombocytopenia and biliverdinaemia. AB - This report describes a case of POEMS syndrome with extremely rare complications of thrombocytopenia and biliverdinaemia. The thrombocytopenia appeared to be due to immunopathogenesis. Steroid treatment resulted in complete disappearance of the biliverdinaemia in this patient as well as symptoms and signs of POEMS syndrome, suggesting that the biliverdinaemia was related to POEMS syndrome. PMID- 8199033 TI - Serum immunoreactive interleukin-6 and C-reactive protein levels in patients with multiple myeloma at diagnosis. AB - Serum bioactive but not immunoreactive interleukin-6 (IL-6), and serum C-reactive protein (CRP), have been reported to be of prognostic significance in multiple myeloma (MM). We measured serum immunoreactive IL-6 by a sensitive enzyme-linked immunosorbent assay in 30 MM patients at diagnosis. In 30% of the patients serum immunoreactive IL-6 exceeded the upper reference limit. The concentrations of CRP and IL-6 showed a linear association. Logarithmically transformed IL-6, CRP and beta 2-microglobulin were significant variables by univariate survival analysis; by multivariate analysis CRP was a slightly stronger prognostic factor than IL-6 and the only one of independent prognostic significance. PMID- 8199034 TI - Clinical and haematological improvement induced by etidronate in a patient with idiopathic myelofibrosis and osteosclerosis. AB - We report a patient with agnogenic myeloid metaplasia associated with debilitating bone pain due to increased bone turnover and osteosclerosis. Treatment with etidronate at a dose of 6 mg/kg per day on alternate months resulted in a complete recovery of bone symptoms and normalization of metabolic parameters of bone turnover; unexpectedly, a sustained haematological improvement was also observed after several months of therapy, suggesting that bone marrow microenvironment improvement was able to restore a nearly normal haemopoiesis. We suggest that diphosphonate therapy may be of value in patients with AMM and increased bone turnover. PMID- 8199035 TI - Possible involvement of protein kinase C activation in down-regulation of CD3 antigen on adult T cell leukaemia cells. AB - The role of protein kinase C (PKC) system on CD3 expression on adult T-cell leukaemia (ATL) was examined. The down-regulation of CD3 on ATL cells is reportedly induced by CD3 down-regulating factor (CD3DF) contained in serum and culture supernatants of leukaemia cells from acute type ATL patients. After we cultured normal PBMC with a PKC inhibitor, H-7, CD3DF activity for PBMC was reduced significantly. Culture with H-7 of HTLV-1 transformed T cells, ATL-2 cells whose CD3 expression had been decreased, led to enhancement of CD3 expression in a time-dependent manner. These findings suggest that CD3DF may play an important role as a PKC system activator, resulting in CD3 down-regulation. PMID- 8199036 TI - Cytogenetic conversion in a case of polycythaemia vera treated with interferon alpha. AB - Polycythaemia vera is a clonal disorder of the haemopoietic stem cell causing a pathologic expansion of the erythroid and sometimes the megakaryocytic and myeloid elements. In order to avoid the possible mutagenic effects of radioactive phosphorus, alkylating agents and hydroxyurea, since 1988 alpha-IFN has been used for the treatment of PV and has been shown to induce and maintain haematological remission. We describe a 24-year-old PV patient with chromosomal abnormalities who achieved not only a reduction of the proliferation of erythroid elements and reticulin content in the bone marrow, but also a complete cytogenetic remission after IFN treatment. PMID- 8199037 TI - Infection by Epstein-Barr virus in Hodgkin's disease is not restricted to the Reed-Sternberg cells. AB - The presence of Epstein-Barr virus (EBV) DNA was analysed by a non-radioisotopic in situ hybridization procedure within eight Hodgkin's disease tissues. Seven specimens contained EBV DNA, that was found not only within the Reed-Sternberg tumour cells, but also, to a varying degree, within the surrounding lymphocytes. The staining was more diffuse in the nodular sclerosis and interfollicular types, whereas it involved only a minority of lymphocytes in cases with mixed cellularity. Appropriate controls established the specificity of these findings. The widespread expression of EBV DNA within Hodgkin's disease tissue heavily underscores the involvement of EBV in the pathogenesis of this illness. PMID- 8199038 TI - Lack of MDM2 amplification in human leukaemia. AB - While deletion or mutation of the p53 gene is one of the most common molecular alterations detected in a wide variety of tumours, it has been shown to occur in only a relatively small percentage of the leukaemia cases examined. However, it may be that other components of the p53 pathway are involved. Amplification of the MDM2 gene has recently been demonstrated in human sarcomas resulting in an increase in MDM2 protein levels. This protein can bind to p53 preventing the transactivation of p53 responsive genes, thus mimicking mutation or deletion of p53. We have investigated the prevalence of MDM2 amplification in human leukaemias. 101 leukaemia or lymphoma samples and nine cell lines were studied using Southern blotting. In no case was MDM2 amplification present. We conclude that MDM2 amplification is not a common event in human leukaemias. PMID- 8199039 TI - GATA-1 is expressed in acute erythroblastic leukaemia. AB - Previous studies have demonstrated the expression of GATA-1 (a DNA-binding nuclear protein) in erythrocytes, megakaryocytes, eosinophils, basophils, mast cells, early marrow progenitor cells and in mouse and human erythroid leukaemia cell lines. We studied 31 bone marrow specimens from patients with acute myeloid leukaemia (AML) for GATA-1 expression by reverse transcriptase/polymerase chain reaction (RT/PCR) analysis. GATA-1 expression was detected in all of the patients with erythroleukaemia, and in one of nine patients with megakaryoblastic leukaemia, but absent from 17 patients with French-American-British (FAB) M1-5 leukaemia. In AML, GATA-1 expression is indicative of differentiation to the erythroid and possibly megakaryocytic lineages, analogous to its expression in normal haemopoiesis. PMID- 8199040 TI - Parvovirus B19-associated haemophagocytic syndrome with prominent neutrophilia. AB - We describe a patient with both haemophagocytic syndrome and acute myocarditis probably associated with parvovirus B19 infection. The patient had a marked neutrophilia instead of neutropenia more usually observed in virus-associated haemophagocytic syndrome (VAHS). Endogenous serum concentrations of macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF), and tumour necrosis factor-alpha (TNF-alpha) were higher than normal, suggesting that these cytokines may be involved in the genesis of the observed syndrome. PMID- 8199041 TI - Incidence of autoantibodies to GPIIb/IIIa in chronic autoimmune thrombocytopenic purpura may be overestimated by the MAIPA. AB - Twenty-one serum samples from patients with thrombocytopenia and five from normal individuals were analysed by the MAIPA test to determine specificity of autoantibody reactivity against platelet glycoprotein IIb/IIIa using murine monoclonal antibodies. The sera were also analysed by dot blot to determine their anti-murine IgG activity. Two of the three patient samples positive in the MAIPA test were positive in the dot blot test for anti-murine IgG activity, and on repeating the MAIPA following preabsorption of the serum with mouse ascites proteins they gave negative results. Reactivity of the sample which did not correct by this procedure was shown to be due to an antiHPA1a alloantibody. The potential problem of human heterophile antibodies reacting with mouse antibodies in the MAIPA has been identified and a modification which corrects this has been demonstrated. PMID- 8199042 TI - Autoimmune haemolytic anaemia presenting 9 years prior to Castleman's disease. AB - Castleman's disease (CD) is a rare disease of unknown aetiology and pathogenesis. We present an unusual case of abdominal CD in whom the first manifestation was an autoimmune haemolytic anaemia presenting 9 years before the diagnosis. The Coombs test became negative 2 months after surgical resection of the mass, suggesting that the mass was the source of the autoantibody. CD may be present in autoimmune haemolytic anaemia in patients with no evidence of any other disease. PMID- 8199043 TI - Domiciliary desensitization therapy for young boys with haemophilia and factor VIII inhibitors. AB - Immune tolerance was induced in five consecutive young boys with haemophilia and factor VIII inhibitors using frequent conventional doses of human factor VIII. All therapy was given at home by parents and the four youngest boys had surgically implanted central venous catheters (Port-a-Cath). Two catheters eventually became infected after 2 and 4 years respectively, otherwise the devices were trouble-free and liked by the families concerned. Regular domiciliary factor VIII therapy in pre-school children is not difficult with an aid to venous access and immune tolerance can be achieved in those developing factor VIII inhibitors. PMID- 8199045 TI - Interleukin-6 serum levels in patients with multiple myeloma. AB - Studying the prognostic value of serum interleukin-6 (IL-6) levels in multiple myeloma, we observed important daily variations in some patients. Therefore a unique serum IL-6 measurement should be interpreted with caution and requires confirmation by multiple determinations performed over a period of several days. PMID- 8199044 TI - Evaluation of mixed chimaerism and origin of bone marrow derived fibroblastoid cells after allogeneic bone marrow transplantation. AB - We assessed the origin of bone marrow derived fibroblastoid cells (BMF) in long term cultures of 13 samples obtained from nine patients after allo-BMT by polymerase chain reaction (PCR) amplification of MCT118, one of the variable number of tandem repeats regions (VNTR). BMF showed a complete recipient pattern in nine samples obtained from seven patients; however, a recipient-predominant mixed chimaeric pattern was detected in BMF from four patients. Also, two of the four patients died with bone marrow hypoplasia. These data suggest that mixed chimaeric pattern of BMF may be correlated with bone marrow hypoplasia. PMID- 8199046 TI - Serum macrophage colony-stimulating factor (M-CSF) levels correlate with clinical response to interferon-alpha in patients with early-stage B-CLL. AB - Interferon-alpha (IFN-alpha) reduces peripheral lymphocyte counts in B-CLL (CLL). In eight patients with stage 0 CLL on IFN-alpha therapy, peripheral lymphocyte counts fell to 61.7 +/- 19.5% of baseline at week 2 (P < 0.01), while serum M-CSF levels rose from 455 +/- 183 U/ml to 686 +/- 110 U/ml (P < 0.05). Neopterin levels also showed a significant rise. M-CSF levels were correlated with clinical response in these patients. Increased production of M-CSF and the activation of mononuclear phagocytes may be involved in clinical responses to IFN-alpha in early-stage CLL. PMID- 8199047 TI - Regulatory and coding regions of the segmentation gene hunchback are functionally conserved between Drosophila virilis and Drosophila melanogaster. AB - The segmentation gene hunchback (hb) is involved in setting up the anterior posterior axis of the Drosophila embryo. It is expressed maternally and zygotically and it plays a key role in integrating the effects of the anterior and posterior maternal systems. The hb gene from D. virilis has previously been cloned and was shown to be well conserved in its coding region, but less so in its upstream region which shows a more patchy pattern of conserved and diverged sequences. This work deals with the functional conservation of hb between the two species. We have mapped two additional regulatory elements for the expression of hb in the early embryo, namely the enhancer for the maternal expression and the enhancer region for the late blastoderm expression. Fragments containing these two elements, the previously identified bicoid dependent element for the early blastoderm expression of hb and the coding region were taken from D. virilis and tested in the D. melanogaster background. We find that all enhancer elements as well as the coding region are functionally conserved between the two species. Comparison of the upstream sequences that include the enhancer region for the late blastoderm expression reveal seven highly conserved blocks. Some of these contain consensus binding sites for transregulatory factors that are likely to control the respective expression domains. PMID- 8199048 TI - Spatial and temporal transcription patterns of the forkhead related XFD-2/XFD-2' genes in Xenopus laevis embryos. AB - Two novel fork head related cDNA sequences, termed XFD-2 and XFD-2', have been isolated from a Xenopus laevis gastrula stage cDNA library. XFD-2 and XFD-2' proteins share 88% sequence identity; a comparison of their fork head domains yields 96% identity. Such close homology suggests that the two genes represent pseudo-allelic variants of a common ancestor and probably arose by the ancient tetraploidization event in this species. Both genes are activated at midblastula transition. Main transcriptional activity is found during blastula and gastrula stages of development; thereafter, there is a gradual decrease of transcripts until somite segregation stages. Whole mount in situ hybridisation of blastula stage embryos reveals that the genes are initially transcribed within the animal hemisphere. Subsequently, we observe their transcription in a circumferential mode along the marginal zone, i.e., within the forming mesoderm. During gastrulation, these cells enter the blastoporus at the ventral, lateral and dorsal sites. At the end of gastrula and during neural stages transcripts are localized within somitogenic mesoderm, notochord, lateral and ventral mesoderm, neural floor plate, spinal cords and in the developing brain. PMID- 8199049 TI - The frizzled gene of Drosophila encodes a membrane protein with an odd number of transmembrane domains. AB - The protein encoded by the Drosophila tissue polarity gene, frizzled (fz), is required for both the intercellular transmission and the intracellular transduction of a tissue polarity signal. In order to study the biochemical characteristics of this rare protein, we constructed a hs-fz fusion gene and transferred this to Drosophila tissue culture cells and embryos. Cell fractionation experiments and immunostaining experiments showed that the Fz protein is an integral membrane protein containing an odd number of transmembrane domains, consistent with previous suggestions that it contains seven transmembrane domains. Immunostaining of pupal wings showed that the Fz protein is evenly distributed throughout the wing arguing that the Fz protein does not act as a graded morphogen. PMID- 8199050 TI - A Drosophila homolog of human proto-oncogene ret transiently expressed in embryonic neuronal precursor cells including neuroblasts and CNS cells. AB - We have identified a Drosophila gene encoding a putative receptor tyrosine kinase by screening a genomic DNA library with a DNA probe for a Drosophila homolog of fibroblast growth factor receptors. The newly isolated gene codes for a transmembrane protein most similar in sequence to a mammalian proto-oncogene ret; thus, the gene was termed Dret. Dret mRNA is transcribed in very small amounts in the embryonic, larval, and pupal stages. Whole mount in situ hybridization experiments revealed that the mRNA is transiently expressed in neuroblasts in early embryos. In late embryos, Dret mRNA was detected in subpopulations of differentiating CNS and PNS cells. In addition, Dret expression was affected in neurogenic mutants. These results suggest that Dret can be considered as a functional homolog of mammalian ret and should play important roles in neurogenesis. PMID- 8199052 TI - Production of dominant female sterility in Drosophila melanogaster by insertion of the ovoD1 allele on autosomes: use of transformed strains to generate germline mosaics. AB - We have cloned a 7 kb genomic fragment containing the dominant female-sterile mutation ovoD1. This fragment confers to transgenic females a sterility phenotype, the severity of which depends both on the genetic background and the ratio of ovoD1 product to ovo+ product. Females containing two copies of the ovoD1 transgene, or those containing one recessive null allele at the ovo locus, are about as sterile as ovoD1 females. Twenty transformed strains were obtained and five of them were tested and shown to be excellent tools for identifying a germline clone of cells sustaining mitotic recombination on the autosomes. One of the tested strains carries an insert on chromosome 4, which enabled us to show that mitotic recombination on that chromosome is not a rare event: it is in fact frequent enough for the maternal effects of the zygotic lethal mutations cubitus interruptus Dominant (ciD) and l(4)29 to be studied. PMID- 8199051 TI - Regional specificity of RAR gamma isoforms in Xenopus development. AB - All retinoic acid receptors (RAR alpha, beta, gamma) have two isoforms, whose function is unknown. We now show that at least for RAR gamma, the isoforms are differentially distributed in the embryo. RAR gamma 1 and RAR gamma 2 are detected in the head region, whereas RAR gamma 2 is the sole isoform expressed in the tail region. Specifically, it is expressed in the chordoneural hinge, a region of the tailbud that has organizing properties. Treatment with high doses of retinoic acid (RA) reduces expression in this region. The results are discussed in terms of the known teratogenic effects of RA in the tail region. PMID- 8199053 TI - Maintenance of the pluripotential phenotype of embryonic stem cells through direct activation of gp130 signalling pathways. AB - Propagation of the undifferentiated pluripotential phenotype of embryonic stem (ES) cells is dependent on the cytokine differentiation inhibiting activity/leukemia inhibitory factor (DIA/LIF). The DIA/LIF receptor complex is a heterodimer of DIA/LIF receptor (DIA/LIF-R) and gp130. The latter is also a component of the interleukin-6 (IL-6) receptor complex. We report that a combination of IL-6 and soluble IL-6 receptor (sIL-6R), which can induce homodimerisation of gp130 and activation of signalling processes, sustains self renewal of pluripotential ES cells. Our findings indicate that the IL-6/sIL-6R complex acts on ES cells through gp130 alone, bypassing DIA/LIF-R, and therefore implicate gp130 as the key component in the signalling pathway responsible for stem cell renewal. PMID- 8199054 TI - XrelA, a Xenopus maternal and zygotic homologue of the p65 subunit of NF-kappa B. Characterisation of transcriptional properties in the developing embryo and identification of a negative interference mutant. AB - We have isolated two clones (XrelA.1 and XrelA.2) from Xenopus ovary representing differentially processed mRNAs homologous throughout their translated regions to the mammalian p65 subunit of NF-kappa B. The transcripts are ubiquitously present throughout development, but are most abundant in late blastulae and gastrulae. Overproduced protein shows nuclear localisation in both oocytes and early embryos. The XrelA.2 product bound to DNA as an oligomer which was not detected in the normal embryo. Two endogenous kappa B-binding complexes were present, showing no stage-specific variation, although one was relatively deficient in posterior regions of the early neurula. They were not disrupted by dimerization with over-expressed XrelA, suggesting that they were not produced by NF-kappa B/Rel/dorsal family members. The transcriptional properties of the cloned XrelA were assayed in intact embryos by co-injecting XrelA mRNA and a linear HIV LTR driven CAT reporter gene. CAT levels were stimulated 20-30-fold by XrelA mRNA levels in the 100 pg range, and this was wholly dependent on NF-kappa B binding sites, and largely dependent on those for SP-1. These results were remarkably reproducible and show that quantitative analysis of transcription factor function is possible in intact developing Xenopus embryos A mutant lacking the transcriptional activation domain antagonised co-injected wild-type XrelA, providing a potential dominant negative p65 mutant for interfering with NF-kappa B function in analysing NF-kappa B function in normal development. PMID- 8199055 TI - Developmental expression of murine retinoid X receptor (RXR) genes. AB - The developmental expression patterns of the three mouse retinoid X receptor genes (RXR alpha, beta and gamma) have been investigated by Northern blotting and in situ analysis of RNA transcript distribution, and compared to those of retinoic acid receptor (RAR) genes. RXR beta showed a diffuse and probably ubiquitous expression pattern at all developmental stages studied. RXR alpha also exhibited a diffuse expression at early developmental stages, but an enhanced in situ labelling was observed during late development in the epidermis and several other squamous epithelia. By contrast, RXR gamma apparently displayed a restricted expression in the myogenic lineage, i.e. in myotomes and subsequently in various differentiating muscles including those of the face and limbs. Apparently RXR gamma was not co-expressed with RAR beta and RAR gamma in these domains. RXR gamma transcripts were developmentally regulated in the otic epithelium, the retina, the pituitary and thyroid glands. In addition, RXR gamma was expressed in several discrete areas of the fetal central nervous system, namely in the diencephalon, the striatum and in part of the ventral horns of the spinal cord. In the two latter domains, there was a precise co-expression with RAR beta transcripts, although with quantitative differences, which suggests a possible preferential heterodimerization between these two retinoic acid receptors in the developing central nervous system. PMID- 8199056 TI - Ethnographic study on childhood diarrhoeal diseases in a rural Nigerian community. AB - Mothers in thirty households in a rural Nigerian community were subjected to ethnographic studies on food handling practices as they relate to diarrhoeal diseases in children. The study had a first phase of three open-ended unstructured interviews each lasting about 2 hours and a second phase of direct observations on food handling practices during preparation, administration and storage by mothers. Results indicated that as many as 20 (66.7%) of the mothers identified diarrhoea as a common cause of childhood diseases. Diarrhoea due to food contamination was recognized by as many as 18 (60.0%) respondents. Four important food handling practices relating to water treatment, handwashing before preparation and feeding, administration and storage were recognized in the first phase but the claimed practices in the first phase differed significantly from the observed practices in the second phase (p < 0.025). Many (32.1%) mothers had contaminating food handling behaviours. The low literacy level, poverty and lack of good personal hygiene among the studies population were the most likely causes of the behaviours observed. PMID- 8199057 TI - Determination of ages of elderly Nigerians through historical events: validation of Ajayi-Igun 1963 listing. AB - We compared ages of 59 elderly Nigerians subjects determined independently by records and historical events to validate the Ajayi-Igun listing of 1963. There was no statistically difference between the mean ages of the subjects as determined by the 2 methods (p > 0.05). In almost 50% of the subjects, the ages were exactly the same by both methods and in 93.2%, the difference in ages was 3 years. There was a high significant correlation between the two methods of age determination (Spearman correlation coefficient rs = 0.989, p < 10(-5)). Our study validate the use of historical listing for accurate age determination in Nigerians and its use is advocated for epidemiologic studies and other demographic needs in circumstances where written records of births are lacking. PMID- 8199058 TI - Hysterosalpingography in investigation of infertility: experience with 248 patients. PMID- 8199059 TI - Acute appendicitis: a prospective study of 54 cases. AB - Fifty-four cases of acute appendicitis were studied prospectively within a period of 11 months spanning between February-September, 1991 and December, 1991 February, 1992. The mean age was 25.4 years with a range of 8-70 years. Ninety percent of the patient were between 11-40 years of age. Male patients accounted for 54% of the cases. Students and civil servants accounted for 68%, while artisans and traders accounted for remaining cases. Low abdominal pain was present in all cases, loss of appetite in 77.7%, and previous history of abdominal pain in 76%. Abdominal tenderness was present in all the patients, rebound tenderness in 77.7%, guarding in 81.5% and Rovsings sign in 50%. In 12 cases (22%) the diagnosis was incorrect 8 of which were female patients. In 9.3% there was perforation. Wound infection and wound dehiscence occurred in 20.4% and 7.4% of the cases respectively. It is concluded from this study that acute appendicitis is commonly encountered in private Hospital, clinical course and postoperative outcome are not different from what obtained in major medical establishments. PMID- 8199060 TI - Studies of maternal plasma renin concentration (PRC) and plasma renin activity (PRA) and cord venous PRC and PRA in the primigravidae delivered under lumbar epidural analgesia. AB - In order to find out whether epidural analgesia, significantly altered the maternal and cord venous Plasma Renin Concentration (PRC) and Plasma Renin Activity (PRA) in the primiparae, a radioimmunoassay measurement of these renin components was carried out on 40 maternal plasma and 18 cord venous plasma samples. The subjects were 20 primiparae who had uneventful antenatal course, 10 of whom were delivered under epidural analgesia, while others (control group) (n = 10) had routine narcotic analgesia in labour. Maternal venous blood samples were taken in the lateral recumbent position at induction of labour, and immediately after delivery, while the cord venous blood samples were obtained just before or immediately after expulsion of the placenta. The mean +/- SEN of maternal pre-induction PRC and PRA, in the control group were 5.56 +/- 0.32 and 3.81 +/- 0.17 nmgl-1hr-1; while the corresponding immediate post delivery values were 5.05 +/- 0.35 and 2.33 +/- 0.06 respectively. In the epidural analgesia group, the mean maternal pre-induction and immediate post-delivery PRC and PRA values were 5.68 +/- 0.22; 3.49 +/- 0.2; and 5.05 +/- 0.35 and 2.36 +/- 0.06 ngml 1hr-1 respectively. The mean cord venous plasma PRC and PRA in the control group were 3.22 +/- 0.17 and 1.18 +/- 0.03 respectively while the corresponding PRC and PRA values for the epidural analgesia group were 2.93 +/- 0.20, and 1.24 +/- 0.04 ngml-1hr-1 respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199061 TI - Perinatal mortality associated with abnormal presentations at the University of Ilorin Teaching Hospital, Ilorin-Nigeria: a prospective study. AB - In a prospective study of perinatal mortality (PNM) rates associated with abnormal (ABN) presentations at the University of Ilorin Teaching Hospital, Ilorin, Nigeria over a four-year period, 1987-1990, it was found that out of 6,000-7,000 yearly deliveries, there was an abnormal presentation in about 4.5% of them. Compared with developed countries, this study has shown that the PNM is still alarmingly in our unit, (a reflection of the trend in Nigeria) and when associated with an ABN presentation the PNM is still higher. The overall PNM has shown a gradual fall from 346 (5.76%) in 1987 to 322 (4.37%) in 1990, but it has been observed that the mortality amongst the ABN presentations is on a steady increase from 52 (16.67%) in 1987 to 66 (18.80%) in 1990. A plea is therefore made for a very close and thorough supervision of the patients during the antenatal period and labour to detect and treat these ABN presentations so as to reduce the perinatal wastage. PMID- 8199062 TI - Genital tuberculosis in infertile women in northern Nigeria. AB - A bacteriological study of 114 infertile patients in Northern Nigeria revealed a prevalence rate for genital tuberculosis of 16.7%. The low incidence of a past history of pulmonary tuberculosis may relate to a gastro-intestinal sources of the infective organisms, illiteracy and delay in seeking medical advice. The presenting features are indistinguishable from those of chronic pelvic inflammatory disease. Since 94.7% of the patients are young (20 to 35 years of age) and the mean duration of infertility long (8.1 years), despite marriage in childhood, infertile women in this environment should be investigated without delay at an earlier age so as to improve diagnosis and subsequent prognosis. PMID- 8199063 TI - A study of malaria parasitaemia in pregnant women, placentae, cord blood and newborn babies in Lagos, Nigeria. AB - The peripheral blood of 101 pregnant women at delivery, their 105 new born babies and the corresponding placental, and cord blood smears were examined cross sectionally for malaria parasites, during a 3 month period (May-July, 1986). The average maternal age was 26.3 years. Positive parasitaemia was found in 2.97% of maternal peripheral thick blood films; in 2.94% of placental smears, and in 0.95% of cord blood films. Congenital malaria did not occur in the babies. PMID- 8199064 TI - EPI sentinel surveillance for Kwara, 1982-1987. AB - A comprehensive review of the EPI sentinel surveillance data for Kwara State, Nigeria was conducted for the years 1982--1987 to evaluate programme impact. Measles vaccination coverage moved up from 26 percent in 1984 to between 54 percent and 58 percent in Ilorin, LGA, Kwara State, Nigeria from 1986 to 1988. During the period of review, the annual number of measles cases and the incidence rate of measles reported by the surveillance system has continued to fall from 1985, the year the revised EPI programme was launched in Ilorin LGA. There was infact a forty-one percent reduction in measles incidence in Ilorin LGA in 1987, but measles is still an important cause of preventable morbidity and mortality in the area. Twenty-two percent of reported measles cases occurred in children under nine months of age, children who are younger than the recommended age of vaccination. Two results expected in a partially vaccinated population, a reduction in measles incidence greater than the level of vaccination coverage and a shift in the age-distribution of measles to older children, have not been observed. Measles control in Ilorin LGA will require a vaccination coverage higher than 58 percent. Also, given the age-specific risk of measles infection there, a measles vaccine that would be effective when given before nine months of age would be an important element in controlling measles transmission. Because the epidemiology of measles in Ilorin is a likely consequence of its urban environment, such a vaccine would represent a significant advance toward the control of measles in urban Africa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199065 TI - Retinoblastomas in Ibadan: treatment and prognosis. AB - This study reviews the influence of different clinicopathological features of retinoblastoma on outcome and prognosis in 44 Nigerian patients. Twenty-five of the patients had a fatal outcome. These patients were younger and more frequently had bilateral retinoblastomas, orbital tumour recurrence and tumour metastases, compared to patients who had disease free survival. Postoperative tumour recurrence occurred in eleven patients and was commoner in patient who had tumour metastases. Tumour metastases occurred in eighteen of the patients. Though there has been an improvement in the prognosis of retinoblastoma at Ibadan with the advent of radiotherapy, the outlook for children with this neoplasm in this environment is still bleak in comparison with what obtains in developed countries. PMID- 8199066 TI - Preterm delivery in Ilorin: multiple and teenage pregnancies as major aetiological factors. AB - This study reports the aetiological factors responsible for 291 preterm births among 5019 deliveries at the University of Ilorin Teaching Hospital (UITH) during a 12-month period. It was found that although preterm babies made up 5.8% of all deliveries, they were responsible for 42% perinatal deaths. Important aetiological factors predisposing to preterm delivery included multiple pregnancy in 41.2% and primiparity in 23.4%. One-fifth of the primiparous were teenage mothers. Other factors included premature rupture of membrane, antepartum haemorrhage, grandmultiparity and eclampsia. It is suggested that early identification, monitoring and intervention in these high risk groups will improve gestational duration thereby reducing morbidity and mortality associated with preterm deliveries. PMID- 8199067 TI - Epileptogenic potential of antimalarial drugs. AB - Available clinical reports suggest that antimalarial drugs may cause epileptic seizures as an adverse reaction in susceptible individuals. Epileptic patients and others with a low seizure threshold appear particularly prone. Antimalarial drugs, particularly chloroquine and mefloquine, should be used with caution by patients with epilepsy. PMID- 8199068 TI - Ectopia cordis in a Nigerian child. AB - A female infant is described with a complete ectopia cordis and a single atrium who presented four hours after birth. There was complete deficiency of the sternum with the absence of pericardium over the heart. There was an associated omphalocele containing an enlarged liver. The infant died 45 hours after birth following an attempt to provide tissue covering. Additional intracardiac anomalies included a ventricular septal defect overriding aorta and total anomalous venous drainage. PMID- 8199070 TI - Continuing medical education. PMID- 8199069 TI - Urethrocavernous and urethrovascular reflux of contrast medium and excretory urogram during retrograde urethrography. AB - Retrograde urethrography is a valuable diagnostic aid of lesions in the urethra. It, however, has inherent hazards in the form of urethrocavernous and urethrovascular reflux of contrast medium, particularly in the presence of inflammatory urethral stricture. A case of massive urethrocavernous and urethrovascular reflux is reported. The dangers of such systemic reflux of urethral contents, including pathogens and contrast material are highlighted. Observation of reflux during retrograde urethrography exposes the patient to bacteremia and sepsis, and this fact must not be overlooked by the radiologist and the clinician. Prompt admission of the patient with adequate prophylactic antibiotic cover is the rule in such situation. PMID- 8199071 TI - The role of the gynaecologist in the diagnosis and management of child sexual abuse. PMID- 8199072 TI - Implications of gestational diabetes for the health of the mother. PMID- 8199073 TI - A randomised trial of routine versus selective counselling in perinatal bereavement from congenital disease. AB - OBJECTIVE: To find out whether routine counselling improves psychological wellbeing after bereavement for fetal abnormality. DESIGN: A randomised trial among bereaved couples who did not demonstrate any unexpected strain or psychopathology after bereavement. SETTING: St. James's University Hospital, Leeds. SUBJECTS: Fifty-seven couples. INTERVENTIONS: Independent counselling by an experienced psychotherapist. MAIN OUTCOME MEASURES: Self-administered questionnaires measuring grief, anxiety and depression and a structured psychological interview 16 to 20 months after the loss. Anniversaries of a death or expected birth date were avoided. RESULTS: There were no differences in outcome between women randomised to the study group or randomised to the control group with respect to grief, anxiety, depression or the results of the structured overview. Among those in the randomised study group, women who attended for counselling had a much better outcome than women who defaulted from counselling. Overall, women who underwent termination of pregnancy did slightly worse than those who had experienced stillbirth or neonatal death. On an informal basis, the clinician concerned believes that he was better able to help bereaved couples as a result of feedback and criticism from the independent counsellor. CONCLUSIONS: (1) The hypothesis that all couples should have independent counselling after prenatal loss for congenital abnormality is unproven, but it is likely that clinicians can benefit from feedback from a counsellor; (2) it is possible that termination of pregnancy is more psychopathogenic than other forms of fetal loss; (3) people who attend for their counselling sessions are probably inherently better able to adjust to bereavement; (4) trials of psychological intervention are feasible, but follow up is either difficult to achieve or expensive. PMID- 8199074 TI - Causes and clinical consequences of Rhesus (D) haemolytic disease of the newborn: a study of a Scottish population, 1985-1990. AB - OBJECTIVE: To identify the reasons behind failures to prevent the development of Rhesus (D) haemolytic disease of the newborn. DESIGN: Retrospective analysis of the case records of all pregnancies that resulted in the birth of an infant with a positive direct antiglobulin test on the cord red cells born to Rh(D) negative women between 1 April 1985 and 31 March 1990. SETTING: Obstetric units in the South East Scotland region and the South East Scotland Regional Blood Transfusion Service Antenatal Laboratory. MAIN OUTCOME MEASURES: The causes and clinical consequences of maternal immunisation to the Rhesus (D) antigen. RESULTS: Between 1985 and 1990, 80 pregnancies resulted in the birth of an infant sensitised with anti-D on the cord red cells. There were no deaths due to haemolytic disease, but considerable resources were deployed in obstetric and neonatal care for these pregnancies. Sufficient data were available to categorise the cause of maternal immunisation in 70 pregnancies. Seven cases were due to immunisation by pregnancy before 1970. Sixty-three cases could be attributed to failure of the Rhesus programme: 10 cases (16%) were due to failure to implement the programme adequately, the other 53 cases (84%) were due to failure of the current guidelines to provide adequate protection. Late immunisation in an uncomplicated pregnancy was the single commonest identifiable cause. CONCLUSIONS: It is likely that substantial further reductions in Rhesus (D) immunisation and haemolytic disease of the newborn will require changes in the Rhesus prevention programme. In particular the role of antenatal prophylaxis requires detailed consideration. PMID- 8199075 TI - Effects of maternal age, parity, and smoking on the risk of stillbirth. AB - OBJECTIVE: To examine the effects of advanced maternal age, nulliparity, and smoking on risk of stillbirth as gestation advances, and to explore possible clinical mediators of these effects. DESIGN: A population based cohort study. SETTING: Sweden, 1983 to 1989. SUBJECTS: All singleton pregnancies of 28 weeks gestation or greater in Nordic citizens at least 20 years old (n = 638,242). MAIN OUTCOME MEASURES: Crude and adjusted risks of stillbirth; gestational age specific risks of stillbirth. RESULTS: Older women (35 years or older), smokers, and nulliparas had elevated risks of stillbirth. The elevated stillbirth risk in smokers was eliminated when women with intrauterine growth retardation, placental abruption, and placenta previa were excluded from the analysis. However, the higher risks in older women and nulliparas persisted even when the analysis excluded women with hypertension, diabetes, placental complications, or growth retardation. Over the course of the third trimester, the age related risk of stillbirth increased, the smoking related risk decreased, and the higher risk in nulliparas showed no clear trend with gestational age. CONCLUSIONS: The association between smoking and stillbirth is explained entirely by the higher incidence of growth retardation and placental complications in smokers. The clinical mediators of the associations of maternal age and parity with stillbirth remain unexplained. Gestational age is an important modifier of the effects of advanced maternal age and smoking on stillbirth risk. PMID- 8199076 TI - A multicentre randomised trial of amniotomy in spontaneous first labour at term. The UK Amniotomy Group. AB - OBJECTIVE: To measure the effect of a policy of routine amniotomy on nulliparous labour. DESIGN: A multicentre randomised controlled trial. SUBJECTS: One thousand four hundred and sixty-three nulliparous women in spontaneous labour at term with intact membranes and a single cephalic fetus. INTERVENTIONS: To have the membranes ruptured routinely early in labour or left intact for as long as possible. MAIN OUTCOME MEASURES: Duration of labour, operative and instrumental delivery rates, use of analgesia, perinatal death, neonatal convulsions and admission to special care. RESULTS: Median duration of labour was 8.4 h in the early rupture group and 9.4 h in the late group. There was no difference in caesarean section, typical odds ratio (OR) 1.1, 95% CI 0.65-1.8; operative vaginal delivery, OR 1.1, 95% CI 0.83-1.5; use of epidural/spinal, OR 0.92 95% CI 0.72-1.2; use of pethidine, OR 1.0, 95% CI 0.79-1.4; neither method of analgesia, OR 0.96, 95% CI 0.68-1.3; blood transfusion, OR 0.71, 95% CI 0.28-1.8. There was no effect on fetal intubation, OR 1.40 (95% CI 0.78-2.5); admission special care, OR 1.28 (95% CI 0.65-2.5). One fetus in the early amniotomy group had neonatal convulsions, but there were no perinatal deaths. PMID- 8199077 TI - The individualised birthweight ratio: a new method of identifying intrauterine growth retardation. AB - OBJECTIVE: To assess the effectiveness of the newly developed individualised birthweight ratio in identifying growth retarded infants. DESIGN: Prospective observational study. SETTING: Obstetric unit, City Hospital Nottingham. SUBJECTS: Two thousand eight hundred and thirty-five women delivered between December 1991 and July 1992 and the infants of 616 of these selected by virtue of their birthweight for gestation and individualised birthweight ratio centile positions. MAIN OUTCOME MEASURES: Skinfold thickness and ponderal index measurements, occurrence of abnormal fetal heart rate patterns, operative delivery due to fetal distress and the need for neonatal resuscitation. RESULTS: Using an individualised birthweight ratio less than the 10th centile as a cut-off results in 25% of those less than the 10th centile of birthweight for gestation being reclassified as normally grown. A slightly larger group are reclassified as small; significantly more of these infants have abnormal ponderal indices and skinfold thicknesses, suffer abnormal fetal heart rate patterns, operative delivery for fetal distress and need neonatal resuscitation than do those who are reclassified as normally grown. CONCLUSION: The individualised birthweight ratio combines the simplicity of birthweight measurement with the accuracy of clinical measurements in the identification of the growth retarded baby. PMID- 8199078 TI - Magnitude and pattern of skeletal response to long term continuous and cyclic sequential oestrogen/progestin treatment. AB - OBJECTIVE: To investigate the magnitude and pattern of the changes in bone mass during five years of continuous and cyclic sequential oestrogen/progestin treatment. DESIGN: Prospective study of normal, early postmenopausal women, initially a double-blind, placebo controlled trial, subsequently an open, controlled investigation. SETTING: Clinical physiology unit of a general hospital. SUBJECTS: Sixty-eight normal, early postmenopausal women. RESULTS: 1. Continuous treatment resulted in significantly higher lumbar spine bone density than did sequential treatment (P < 0.001). Lumbar spine bone density was 19% and 15%, respectively, above that of untreated women after three years and onwards, and 10% and 6%, respectively, above the initial value; 2. Both regimens induced a more pronounced rise in lumbar spine bone density than in forearm bone mineral content (P < 0.001); 3. The spontaneous decline (without treatment) in lumbar spine bone density and forearm bone mineral content averaged 1.86% and 1.90% per year, respectively. 4. There was a significant bone loss from the lumbar spine during the last year of active treatment (P < 0.001). This would suggest that lumbar spine bone density rises to a certain level and subsequently declines. However, neither data pooled before computation nor data processed individually for each patient over five years allowed for any definite conclusions regarding the pattern of the long term skeletal response to combined oestrogen/progestin treatment. CONCLUSION: Five years treatment with oestradiol/norethisterone resulted in a substantial gain in bone mass. The highest values were found in the axial skeleton with daily administration of 2 mg oestradiol and 1 mg norethisterone. It is likely that bone mass after an absolute rise begins to decline after about four years of treatment. PMID- 8199079 TI - Expression of transforming growth factor-alpha in the normal cervix and in benign and malignant lesions of the uterine cervix. AB - OBJECTIVE: To investigate the expression and distribution of transforming growth factor-alpha (TGF-alpha) in the normal cervix and in benign and malignant lesions of the uterine cervix. SUBJECTS AND METHODS: Immuno-histochemical reactivity with a monoclonal antibody against TGF-alpha was examined in tissue specimens from 15 normal cervices, six cervical polyps, four cervical condylomata acuminata, 34 cervical intra-epithelial neoplasias, 35 invasive squamous cell carcinomas, five adenocarcinomas, and three mixed adenosquamous carcinomas. RESULTS: Normal squamous cells of the exocervix were found to be negative for TGF-alpha immunoreactivity, whereas reserve cells and metaplastic squamous cells in the transformation zone were positive for TGF-alpha. Although TGF-alpha immuno reactivity was variable in the cervical condylomas, most cases of cervical intra epithelial neoplasia with or without koilocytotic atypia were negative for TGF alpha. In the invasive carcinomas, however, TGF-alpha immuno-reactivity was observed in 17 out of the 35 cases of squamous carcinoma, and in all cases of adeno- and adenosquamous carcinomas. In addition, intense TGF-alpha immuno reactivity was found in clinically advanced tumours. CONCLUSION: These results suggest that the expression of TGF-alpha is associated with squamous metaplasia in the normal cervix, and that TGF-alpha may play an important role in cervical carcinogenesis, especially in its progression. PMID- 8199080 TI - Persistent gestational trophoblastic tumour with partial hydatidiform mole as the antecedent pregnancy. AB - OBJECTIVE: A 16 year review of persistent gestational trophoblastic tumour when the antecedent pregnancy was a partial hydatidiform mole. DESIGN: Cases of persistent gestational trophoblastic tumour with partial hydatidiform mole as the antecedent pregnancy were reviewed for the period 1976 to 1992. DNA ploidy was analysed by flow cytometry. SETTING: A University Hospital which is a reference centre for gestational trophoblastic tumour. SUBJECTS: The case notes of 207 women with persistent gestational trophoblastic tumour were reviewed. MAIN OUTCOME MEASURES: A rise (or failure to fall) of beta hCG titre, or sign of metastasis. RESULTS: Six (2.9%) women had partial hydatidiform mole as the antecedent pregnancy and all were initially judged to be low risk. However, two developed pulmonary metastasis; one woman developed persistent gestational trophoblastic tumour shortly after a hysterotomy, and none developed choriocarcinoma. The geometric mean of serum beta hCG concentrations at the initiation of chemotherapy was 868 mIU/ml (95% CI 114-1524). Of the six women, one achieved remission after total abdominal hysterectomy, and five after chemotherapy. The mean interval from starting treatment to remission was 68 days (95% CI 27.9-108.0). The initial beta hCG titre and interval were not statistically different from those found in cases of persistent gestational trophoblastic tumour when the antecedent pregnancy was not partial hydatidiform mole. Of the six, the DNA content was triploid in three and diploid in two. One of the two diploid cases required multiple courses of chemotherapy to achieve remission. CONCLUSION: Partial hydatidiform mole can have malignant sequelae and can develop very soon after treatment. Its DNA content can be either diploid or triploid, the lungs being the most common site of metastasis. After evacuation of partial hydatidiform mole, immediate chest X-ray and regular follow up of the serum beta hCG level is necessary. PMID- 8199081 TI - The value of an absorbable adhesion barrier, Interceed, in the prevention of adhesion reformation following microsurgical adhesiolysis. AB - OBJECTIVE: To determine whether Interceed, an absorbable adhesion barrier, confers any additional benefit over conventional microsurgery, including the use of an adjuvant (hydrocortisone), in the prevention of adhesion reformation after pelvic microsurgery. DESIGN: A prospective, randomised, controlled study. SETTING: Jessop Hospital for Women, Sheffield, UK. SUBJECTS: Twenty-eight women who underwent pelvic microsurgery for infertility or for chronic pelvic pain and who had bilateral pelvic adhesions and deperitonealised areas following adhesiolysis. INTERVENTIONS: Following microsurgical adhesiolysis, one side of the pelvis was randomised to have its deperitonealised areas covered with Interceed, whereas the contralateral side served as the control. A second look laparoscopy was carried out 3 to 14 weeks after microsurgery to evaluate adhesion reformation. MAIN OUTCOME MEASURE: The amount of adhesion reformation at second look laparoscopy compared with the amount of deperitonealised area exposed following microsurgical adhesiolysis. RESULTS: The use of Interceed resulted in a significant reduction of adhesion reformation over and above that achieved by conventional microsurgical techniques with hydrocortisone as an adjuvant. CONCLUSION: Interceed, an absorbable adhesion barrier, is of value in the prevention of adhesion reformation and may be used in conjunction with hydrocortisone instilled intraperitoneally at the conclusion of microsurgery. PMID- 8199082 TI - Amniotic fluid temperature change during first trimester amnifiltration. PMID- 8199083 TI - The effect of cervical contractions on the generation of intrauterine pressure during the latent phase of labour. PMID- 8199084 TI - The visual evoked potential in the assessment of central nervous system effects of pre-eclampsia: a pilot study. PMID- 8199085 TI - Polycystic ovaries and endometriosis: a possible connection. PMID- 8199086 TI - Benign thymoma and resistant ovary syndrome. PMID- 8199087 TI - Adenomyosis misdiagnosed in an infertile patient resulting in endometrial excision. PMID- 8199088 TI - Vesico-uterine fistula occurring in a woman with a previous caesarean section and two subsequent normal vaginal deliveries. PMID- 8199089 TI - Phenytoin prophylaxis in severe pre-eclampsia and eclampsia. PMID- 8199090 TI - Emergency contraception: time for de-regulation? PMID- 8199091 TI - A nonpenetrating fetal scalp electrode. PMID- 8199092 TI - Hyperammonaemia after transcervical resection of the endometrium. PMID- 8199093 TI - Ambulatory blood pressure measurements in pregnancy. PMID- 8199094 TI - A randomized prospective study comparing the new vacuum extractor policy with forceps delivery. PMID- 8199095 TI - Zoladex and Gynaecology: A Successful Partnership. Proceedings of a meeting. Montreal, Canada, 10 October 1993. PMID- 8199096 TI - Thinning the endometrium prior to ablation: is it worthwhile? PMID- 8199097 TI - Goserelin (Zoladex) versus danazol for endometriosis: the North American experience. PMID- 8199098 TI - Goserelin (Zoladex) and the skeleton. PMID- 8199099 TI - Advanced endoscopic techniques used in dysfunctional bleeding, fibroids and endometriosis, and the role of gonadotrophin-releasing hormone agonist treatment. PMID- 8199100 TI - Can hormone replacement therapy be used during medical therapy of endometriosis? PMID- 8199101 TI - Pituitary down-regulation with goserelin (Zoladex) for in vitro fertilisation. PMID- 8199102 TI - Deferred versus immediate surgery for uterine fibroids: clinical trial results. PMID- 8199103 TI - Goserelin (Zoladex) and the anaemic patient. PMID- 8199104 TI - Imaging posterior uveal melanomas. PMID- 8199105 TI - What is the best intraocular lens? PMID- 8199106 TI - Possibilities and limitations of radioimmunoscintigraphy and conventional diagnostic modalities in choroidal melanoma. AB - A prospective clinical study to assess the value of immunoscintigraphy with a monoclonal antibody (MoAb) against high molecular weight melanoma associated antigen (225.28S) was performed in 43 patients with choroidal melanoma; in six patients with a lesion suspected of being choroidal melanoma, and in seven patients with a benign lesion simulating a choroidal melanoma. The results of immunoscintigraphy in choroidal melanoma were compared with results of conventional diagnostic modalities like ultrasonography and fluorescein angiography. Planar scintigraphy showed a detection rate of 49% which is comparable with other studies. The detection with scintigraphy was correlated to the size of the choroidal melanoma. The use of single photon computed tomography did not increase the sensitivity of immunoscintigraphy. Ultrasonography yielded a correct diagnosis in 37 of 42 melanomas (88%). With fluorescein angiography a correct diagnosis was obtained in 11 of 30 melanomas (36.6%). The value of immunoscintigraphy with MoAb 225.28S in small choroidal melanomas is limited; its reliability increases in large tumours. Immunohistochemistry with MoAb 225.28S showed antigen expression in 95% of the stained tissue specimens of choroidal melanoma. PMID- 8199107 TI - Compared optical performances of multifocal and monofocal intraocular lenses (contrast sensitivity and dynamic visual acuity) AB - The functional results (contrast sensitivity and dynamic visual acuity) of 19 multifocal (3M design) and 14 all polymethylmethacrylate biconvex monofocal intraocular lenses (IOLs), 6 mm in optical diameter were compared. Best corrected visual acuity was > or = 8/10 (Monoyer chart) Parinaud 2 in all cases. Major differences of functional performance in favour of monofocal IOLs were found outside standard conditions of vision (low contrast and illumination levels). A significant difference in contrast sensitivity was found for each spatial frequency in favour of multifocal IOLs (0.0016 < p < 0.05). Mesopic vision was statistically higher in the monofocal IOL group (p = 0.0015). Moreover, dynamic visual acuity allowed accurate evaluation of the difference in performance between these two models of implant. In view of these results multifocal IOLs should be reserved for patients with normal psychosensitive adaptation; an ocular pathology that could alter contrast sensitivity or mesopic vision is a contraindication for multifocal IOLs. PMID- 8199108 TI - Prognostic factors in primary malignant melanoma of the conjunctiva: a clinicopathological study of 256 cases. AB - A series of 256 consecutive cases of invasive primary conjunctival malignant melanomas was examined to identify clinical and histopathological prognostic factors. The follow up period varied between 0.3 and 45.9 years (mean 9 years, median 6.3 years). The 5 year survival rate was estimated at 82.9%, the 10 year survival rate at 69.3%. Multiple regression analysis with the Cox proportional hazards model was used to assess sex, age, and a number of baseline features of conjunctival malignant melanoma as possible prognostic factors influencing melanoma related mortality. In assessing each potential prognostic factor, the effects of all other factors were taken into account in the modelling process. Tumours in unfavourable locations--that is, those involving the palpebral conjunctiva, fornices, plica, caruncle, and lid margins, were associated with 2.2 times higher mortality compared with (epi)bulbar melanomas. Patients with mixed cell type tumours had about three times higher mortality compared with those with pure spindle cell melanomas, and histological evidence of lymphatic invasion by tumour cells was also a prognostic feature, carrying a fourfold increase in the death rate. Multifocal tumours were associated with a fivefold increase in mortality among those with tumours in favourable (epi)bulbar locations, but were not prognostic in patients with melanomas in unfavourable sites. The death rate was significantly higher in those with initial tumour thickness of more than 4 mm, but only among patients with unfavourably located melanomas. Sex, age, and clinical origin of the tumour (primary acquired melanosis, pre-existing naevus, or de novo) were not useful prognostic indicators in this study. PMID- 8199109 TI - Clinicopathological review of 1146 enucleations (1980-90). AB - The clinicopathological data of 1146 enucleated eyes obtained from 1146 patients (485 females and 661 males; mean age 57.4 (SD 21.6) years) between 1980 and 1990 were reviewed. The most common underlying diseases included trauma (37.4%), malignant tumours (19.6%), systemic diseases (diabetes, vascular diseases) (17.1%), surgical diseases (retinal detachment, glaucoma, cataract, corneal dystrophy) (14.1%), infection and inflammation (7%). The most frequent indications for enucleation were secondary angle closure glaucoma (34.9%), ocular malignant tumours (21.7%), atrophia or phthisis bulbi (18.7%), ocular infectious or inflammatory disease (14.7%), and recent trauma (enucleation was performed within the first month after trauma) (11.2%). Histopathologically, diagnoses included secondary angle closure (691 eyes or 60.3%), rubeosis iridis (550 or 48%), endothelialisation of the iridocorneal angle (198 or 17.3%), and retrocorneal membrane (143 or 12.5%). These data indicate that rubeosis iridis, often followed by irreversible secondary angle closure, represents the most common pathogenetic reason for enucleating eyes. Management procedures must be directed towards the prevention or consequent therapy of rubeosis iridis. PMID- 8199110 TI - Feuds between opticians and ophthalmologists. PMID- 8199112 TI - Surgical correction of ptosis in ocular fibrosis syndrome. AB - The surgical management of ptosis is reported in seven patients suffering from the ocular fibrosis syndrome. Satisfactory results were obtained with bilateral Crawford type brow suspension with autologous fascia lata in six patients and bilateral Fox type brow suspension with stored fascia lata in a young child. As patients with ocular fibrosis syndrome usually exhibit little or no Bell's phenomenon, corneal exposure can become a problem after brow suspension. It was recommended that the lids are left just closed on the operating table at the end of the operation. None of the patients required a subsequent procedure to lower an overcorrection of the ptosis. The routine prescription of ocular lubricants for 2 months after ptosis correction is advocated. Urgent brow suspension in young children using non-autologous materials should only be considered if there is a risk of amblyopia. PMID- 8199111 TI - Fibrous dysplasia of the orbit. AB - Twelve patients with fibrous dysplasia of the orbit are reviewed and the ophthalmic findings described. Three case histories are presented in detail. Six patients were managed conservatively; four have shown radiological progression of the disease. Six patients underwent surgery. A conservative procedure, comprising debulking dysplastic bone, was carried out in four--all required further surgery including radical excision in two patients. Two subjects had primary radical operations. No recurrence was encountered in the four patients who had undergone radical surgery. It would appear that fibrous dysplasia is not a disease confined to adolescence but may continue into adulthood, and even middle age. Patients may never require surgery, but require follow up for late progression. If surgical intervention is deemed necessary, an attempt should be made to excise all dysplastic bone, since progression of the disease after conservative surgery is relatively common. PMID- 8199113 TI - Prevalence of blindness and low vision of people over 30 years in the Wenchi district, Ghana, in relation to eye care programmes. AB - A population based survey on the prevalence of major blinding disorders was conducted in the Wenchi district in central Ghana between March and May 1991. In 10 villages, 1425 people of 30 years and older were screened, using the WHO eye examination record. The prevalence of bilateral blindness above 30 years proved to be 1.7% (best acuity < 3/60): the prevalence of low vision above 30 years was 2.0% (best visual acuity 6/18 to 3/60). The causes of blindness were determined as cataract (62.5%), onchocerciasis (12.5%), corneal opacity (non-trachomatous) (8.2%), refraction anomalies (4.2%), phthisis bulbi (4.2%), optic atrophy (4.2%), and vascular retinopathy (4.2%). In the Wenchi district, 1.0% of the population over the age of 30 years was found to need a cataract extraction because of blindness of both eyes. Another potential 1.0% needs a cataract extraction because of low vision. A minor second study (n = 149) was undertaken in the same district, but in a village in an area near the Black Volta river in which onchocerciasis is endemic. The prevalence of blindness (8.1%) and low vision (3.4%) caused by onchocerciasis and cataract both proved to be higher. The survey provided the basis for a preventive and curative eye care programme. PMID- 8199114 TI - Superior oblique tendon lengthening for acquired superior oblique overactions. AB - Two patients who presented with compensatory head postures and diplopia are described. They both had marked unilateral superior oblique overaction, in one patient due to a large, incomitant skew deviation. Each underwent a superior oblique tendon lengthening procedure using a segment of silicone 240 retinal band as an expander, in combination with a contralateral superior rectus recession. Both achieved an excellent result with an improvement of the compensatory head posture and an increase in the field of binocular single vision. This surgical procedure is proposed as an option in the management of superior oblique overaction, including certain cases of skew deviation. PMID- 8199115 TI - Localised wedge shaped defects of the retinal nerve fibre layer in glaucoma. AB - Glaucoma can be associated with a diffuse or localised loss of the retinal nerve fibre layer (RNFL). This study evaluated the wedge shaped localised RNFL defects. Red free wide angle RNFL photographs of 421 patients with glaucoma and 193 normal subjects were examined. Localised RNFL defects were described for one eye of the normal group and for 20% of the patients with glaucoma. They were usually located in the inferior temporal and superior temporal fundus regions. Within the glaucoma group, localised RNFL defects occurred most often (p < 0.05) in normal pressure glaucoma, followed by primary open angle glaucoma, and finally secondary open angle glaucoma. They were positively associated with disc haemorrhages. The localised RNFL defects had a high specificity to indicate optic nerve damage. The nerve fibre layer defects occurring more likely in mild rather than advanced glaucoma, they were helpful in the diagnosis of early glaucoma. The association between localised RNFL defects and disc haemorrhages and the varying frequency of localised RNFL defects in different types of glaucoma may be important diagnostically and pathogenetically. PMID- 8199116 TI - Correlation of peripheral displacement thresholds and optic disc parameters in ocular hypertension. AB - Both peripheral displacement thresholds and measurement of optic disc parameters have been advocated in the early diagnosis of glaucoma at the stage before scotomata are detected on conventional visual field assessment. The peripheral movement displacement thresholds were measured in 50 eyes of 50 patients with ocular hypertension and a significant correlation was found with neuroretinal rim areas measured using a computerised image system. There was also a significant correlation with optic disc diameter but no correlation with cup-disc ratio. The results support the proposition that measurement of peripheral movement displacement thresholds may be a useful tool in the detection of early glaucomatous optic nerve damage. PMID- 8199117 TI - Oculocutaneous manifestations in xeroderma pigmentosa. AB - Xeroderma pigmentosum (XP) is a rare genetic disease characterised by defective DNA repair leading to clinical and cellular hypersensitivity to ultraviolet radiation. The oculocutaneous features of 10 patients with XP were studied retrospectively. General features included parental consanguinity (40%), familiarity (60%), onset of symptoms in first 2 years (50%), malignant skin neoplasms (60%), and carcinoma of the tongue (20%). Among the ocular features, 50% of patients presented with photophobia. Lid freckles or atrophic skin lesions were seen in all patients. Lower lid tumours were seen in 30%, chronic conjunctival congestion in 40%, corneal opacification in 40%, squamous cell carcinoma of limbus in 20%, bilateral pterygium in 40%, and visual impairment in 50%. The clinical features (ocular and cutaneous) of the cases are discussed. PMID- 8199118 TI - Genetic and clinical determinants for the T cell mediated immune response against the cornea specific protein BCP 54. AB - T cell mediated immune responses against the cornea specific protein BCP 54 have been observed in patients with uveitis, Fuchs' heterochromic cyclitis, and corneal disease. The pathophysiological role of this anti-BCP 54 response in corneal disease is not known. In order to ascertain whether the presence of such an immune response is related to the corneal disease itself or related to genetic influences, the anti-BCP 54 response was determined in 104 patients with severe corneal disease, using a monocyte migration inhibition assay. The results were compared with the presence of a variety of ocular parameters as well as with the distribution of HLA antigens in these patients. While only 7% of healthy controls responded to BCP 54, 37% of the patients showed a positive response (p = 0.002); in particular, patients with previous graft rejection, non-herpetic keratitis, and bullous keratopathy reacted against BCP 54. No relation with known risk factors for corneal transplantation, such as corneal neovascularisation, was observed. No significant association with the presence of any of the HLA antigens was observed. It was concluded that the main inducer of an anti-BCP 54 response is corneal disease itself, and that the presence of corneal disease is able to break the immunological privilege typical of normal corneas. PMID- 8199119 TI - Effects of irrigation solutions on corneal endothelial function. AB - Rabbit corneas were perfused in vitro with an irrigation solution for 90 minutes. This was followed by 6 hours of perfusion with tissue culture medium TC199 during which endothelial function was assessed by monitoring rates of swelling during a period of perfusion in the absence of bicarbonate ions, and subsequent rates of thinning when bicarbonate ions were restored to the perfusate. Corneal thickness (measured with an ultrasonic pachymeter) immediately following excision was 401 microns (SD 19, n = 23). During the 90 minute perfusion at 35 degrees C, corneas exposed to balanced salt solution (BSS), Hartmann's solution or 0.9% NaCl (all initially at room temperature) swelled, respectively, at 14 (SD 2.3, n = 4), 11 (SD 2.6, n = 4), and 70 (SD 4.3, n = 4) microns/h. Cold Hartmann's solution (initially at 4 degrees C) caused corneas to swell at 9 (SD 2.3, n = 4) microns/h. On the other hand, corneas perfused with BSS Plus thinned at 9 (SD 3.4, n = 4) microns/h and TC199 with Earle's salts had little effect on thickness. Rates of swelling and thinning during the following assessment perfusion showed no apparent effects of prior exposure to any of the irrigation solutions on the barrier properties or pump function of the endothelium. Despite this, the increased thickness of corneas exposed initially to BSS, cold Hartmann's solution, or 0.9% NaCl was not fully reversed, even by the end of the 6 hour assessment perfusion. In contrast, the swelling observed in corneas exposed to Hartmann's solution at room temperature was reversed and these corneas had returned to their normal thickness by the end of the assessment period. All corneas, even those exposed to 0.9% NaCl, had an intact endothelial mosaic with no evidence of damage or cell loss, although morphological differences in cell shape and the appearance of cell borders were evident compared with freshly isolated cornea. PMID- 8199121 TI - Papilloedema and hydrocephalus in spinal cord ependymoma. PMID- 8199120 TI - Fuchs' heterochromic cyclitis: review of the literature on the pathogenetic mechanisms. PMID- 8199122 TI - Metastatic prostatic adenocarcinoma presenting as complete ophthalmoplegia from pituitary apoplexy. PMID- 8199123 TI - Conjunctival melanoma after excision of a lentigo maligna melanoma in the ipsilateral eyelid skin. PMID- 8199124 TI - Aggressive orbital lymphoma in AIDS. PMID- 8199125 TI - Ocular pulse measurements to assess pulsatile blood flow in carotid artery disease. PMID- 8199126 TI - Tumor infiltration of the vena cava in nephroblastoma. AB - Although operative treatment of Wilms' tumors has become more straightforward as a result of advances in preoperative treatment and precise diagnosis, vascular involvement by the tumor can cause serious problems at operation. These problems can be more easily managed if they have been identified pre-operatively and the level of the intravascular tumor thrombus has been defined. In this study we propose a classification of intravascular involvement of Wilms' tumors suggesting the clinical consequences and operative strategy. In our series of 84 patients we treated 7 (8.3%) with preoperatively diagnosed intracaval tumor thrombus using ultrasound as the most sensitive non-invasive diagnostic technique. The surgical therapy depends on the stage; stage III and stage IV should be operated in cooperation with the cardiovascular surgeon in deep hypothermic circular arrest. PMID- 8199127 TI - Adrenocortical tumors in children: a report of 12 cases. AB - Adrenocortical tumors in children are extremely rare, accounting only for 0.3 0.4% of all neoplasms in this age. Most frequently they secrete hormones, resulting in virilization, Cushing's syndrome or feminization, while the non functioning ones are unusual. The authors describe 12 cases observed in 13 years (1976-1989), with a mean age of 5 years. 9 cases showed virilization, 4 presented with Cushing's syndrome and in 5 patients an abdominal mass was palpable. One case was affected by Beckwith-Wiedemann's syndrome. I.V. urography was performed in 8 patients, arteriography in 4 and since 1982 all patients were submitted to abdominal sonography and CT scan or MR imaging. Urinary 17-ketosteroids, 17 hydroxycorticoids and serum testosterone and cortisol were tested in all children. Dexamethasone suppression test was performed in 7. All patients were treated with surgery which seems to be the most suitable treatment, while the real effectiveness of treatment by drug therapy with suppressors of steroidogenesis is not confirmed in children. Histopathological examination showed typical features of adenoma in 5 cases, of adenocarcinoma in 4, while three cases revealed border line forms classified as "atypical adenomas". At the moment 10 patients are alive with a follow-up ranging from 18 months to 14 years, while 2 children with adenocarcinoma are dead. PMID- 8199128 TI - The effect of intrauterine vascular compromise on further development of corpus spongiosum and urethra. AB - An in-utero experimental study was performed to evaluate the effects of intrauterine vascular compromise on further development of corpus spongiosum and male urethra. Thirty time-mated pregnant New Zealand white rabbits on their twenty-third day of gestation were used. Deterioration of the blood supply of the corpus spongiosum and urethra was attempted by electrocauterizing the perineum adjacent to the root of the phallus without damaging the corpus spongiosum and urethra, under the operating microscope. A bipolar cautery was carried out using a specially designed forceps having 100 microns interspaced fixed tips. Five experimental and seven control live male litters were delivered at term by Cesarean sections. Their anogenital regions were examined histopathologically. While the corpus spongiosum extended as long as the corpus cavernosum to the tip of phallus in control litters, the corpus spongiosum ended under the skin in one of the experimental group and in the other four was shorter than the corpus cavernosum. In the latter group, no histopathological evidence of tissue destruction which might be related to electrocauterization, was found. Similar to the pathogenesis encountered in intestinal atresia, a vascular insult which might occur even after the completion of organogenesis, may affect the fate of the corpus spongiosum and urethra. Localized ischemia resulting from local vascular insults may explain, at least in theory, the pathogenesis of some congenital anomalies of corpus spongiosum and urethra such as hypospadias. PMID- 8199129 TI - Trans-axillary transpleural sympathectomy for Palmar hyperhidrosis in children--a 3 to 7 year follow-up of 9 cases. AB - Primary palmar hyperhidrosis can be a most unpleasant and distressing affliction. When normal daily activities, viz. writing, schoolwork, are interfered with and other treatments have failed, surgery is indicated. Between 1983-1987 9 children (6 F, 3 M), mean age 10.2 years (range 5-14 years) underwent bilateral transaxillary sympathectomy, 4 simultaneous and 5 1-4 weeks apart. On 14 sides a standard excision of dorsal ganglia (DG) 2, 3, and 4 was performed. The technique of lateral displacement of the sympathetic chain after transection distal to DG 4 and division of preganglionic fibres of DG 4, 3 and 2 was used on 5 sides. In addition to clinical evaluation a pilocarpine stimulation test was performed on the palms of the hands before and at follow-up 3-7 years after surgery. 17/18 hands appeared sympathectomised at early follow-up. One inadequate result required reoperation. Other complications included 2 Horner's syndromes--1 transient and 1 mild but permanent; 3 temporary intercostobrachial paraesthesias, 2 mild late recurrences of sweating and 2 compensatory increases in sweating. In 14 palms where sweat volume was measured before and 3-7 years after surgery there was a mean decrease in sweat of 84% (mg), those sweating the most prior to surgery having the best response. In 2 further palms insufficient sweat was obtained for testing. All but 1 considered the procedure worthwhile. Transaxillary transpleural sympathectomy is a safe, effective, and cosmetically acceptable operation to control symptoms of excessive palmar sweating.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199130 TI - Desepiphysiodesis--elimination of partial premature epiphyseal closure. Experience of 17 cases. AB - Between 1975 and 1990, 17 growth plates have been operated on by epiphyseal bridge resection. The children were from 4 years and 10 months to 13 years and 10 months old. The etiology of partial closure was traumatic (10 times), caused by therapeutic mistakes (3 times), septic osteomyelitis (1 case), purpura fulminans (1 case), unknown (2 cases). There was always length discrepancy or deformity of bone. The regions that have been subjected to treatment were distal femur, proximal tibia, distal tibia, distal radius. Evaluation of the bone bridge was made by tomoscintigraphies and recently by MR imaging and computed tomoscintigraphy. The bone bridge size was from 2.5% to 60% of the growth plate surface; surgical technique consists of resection of bone bridge connecting epiphysis and metaphysis which is replaced by methyl metacrylate. In 16 cases simultaneous corrective osteotomy was performed. Results are poor, there were only two good results and 8 failures; seven results were medium. The failures can all be explained by mistakes in technique or indication, except one. Indications are post-traumatic narrow bridges in young children. It would be useful to know the vitality of the residual growth plate. PMID- 8199131 TI - Bilateral adrenal neuroblastoma. AB - Two cases of bilateral adrenal neuroblastoma in infants are reported. The first patient presented with abdominal distension due to metastatic hepatomegaly and the second patient was found because of elevated urinary VMA by VMA mass screening system. Both were under one year of age and were classified as stage IVs neuroblastoma. In each case unilateral adrenalectomy was performed and the contra-lateral adrenal tumor was observed. The remaining tumors slowly decreased in size and clinical progress was good. A review of published cases of bilateral adrenal neuroblastoma suggests that the characteristics of this disease are age less than 1 year, stage IVs, and good prognosis. PMID- 8199133 TI - Amputation of penis after circumcision--penoplasty using expandable prosthesis. AB - A two-year-old boy was referred for correction of an amputation of penis following ritual circumcision. The reconstruction involved mobilization of the profound part of corpora cavernosa and coverage by a vascularised flap taken from the hypogastric area through the use of a sub-cutaneous expandable prosthesis. After two years, appearance of the neo-penis is satisfactory considering the initial lesions. PMID- 8199132 TI - Reconstruction of the penis after necrosis due to circumcision burn. AB - Penile necrosis secondary to circumcision by an electrical scalpel in a 2 years and-2-months-old boy occurred. After healing of the electric burn only stumps of the erectile bodies and strictured urethral meatus remained. Penile shaft reconstruction by corpora mobilisation and detachment of the crura from the pubo ischial rami was performed. This procedure gained 6 cm of a new length of the penis. To prevent readhesions to the pubo-ischial rami the penis was buried in a scrotal tunnel. Six months later the denuded shaft was resurfaced with one split thickness skin graft and a zigzag seam on the ventral side was made. The patient voids with good stream, has spontaneous erections and nocturnal emissions. During 10 years of follow-up after the reconstruction two complications, namely a stricture of the urethra and a slight dorsal tethering of the penis caused by a scarred pubic skin were treated. The problems of reconstruction and resurfacing of the penis in childhood are discussed. PMID- 8199134 TI - Ano-rectal malformation and recurring orchioepididymitis in infants. AB - The case of a newborn boy is reported, incorrectly diagnosed as anal agenesis without urethrae fistula and treated by anoplasty. The patient later suffered several episodes of urinary infection and left epididymo-orchitis orchioepididymitis, reflux of contrast being shown at micturating cystourethrography into the right vas deferens, the seminal vesicle, epididymis and left testicle. Rectal endoscopy revealed a rectourethral fistula, confirmed by fistulography. The patient improved after surgical removal of the fistula. PMID- 8199135 TI - "H-type" urethrorectal communication and complete urethral stenosis with unilateral renal agenesis. AB - Congenital "H-type" urethrorectal communication with complete urethral stenosis is extremely rare in the pediatric population. The evaluation and surgical treatment of a "H-type" urethrorectal communication with complete urethral stenosis presenting in a 4-month-old infant is described. Additionally, he had a left renal agenesis and anal stenosis. PMID- 8199136 TI - Accessory lower limb in a newborn with multiple malformations. AB - Accessory lower limbs are rare anomalies that are associated with other severe malformations. The authors describe a case of this type and discuss the pathogenetic and classification problems surrounding these malformations in the light of the limited number of the other cases reported in the literature. PMID- 8199137 TI - Surgically treated dipygus (caudal duplication) and review of the literature. PMID- 8199138 TI - Long-term follow-up of Nissen fundoplication. AB - A study of 68 children under 7 years of age, who had had an abdominal approach Nissen operation, with a postoperative follow-up of between 4 and 14 years, is presented. The patients were classified into three groups, according to radiological appearance and cuff site. In the first group (40 patients) the cuff was intraabdominal and competent; in the second group (22 patients) the cuff was partially displaced into the thorax and was competent. 92% of the patients of these groups are currently asymptomatic and none required reoperation. In the third group (6 patients), there was disorganization of the cuff, together with its displacement into the chest, recurrence of symptoms and the authors recommended reoperation. Nissen's operation is an effective treatment for gastrooesophageal reflux in children unresponsive to medical treatment. Although displacement occurs frequently, valve competence is unaffected except in those where the cuff has disappeared and there is herniation into the thorax in which case reoperation is necessary. PMID- 8199139 TI - Recurrent bilateral coronoid hyperplasia: an unusual case. AB - A case of bilateral coronoid hyperplasia is presented. The possible aetiology of this rare condition is discussed. This case is unusual in that true synovial joints were demonstrated bilaterally between the coronoid processes and the zygomatic bones and following a bilateral coronoidectomy, the coronoid hyperplasia with marked limitation of jaw opening fully recurred, which has not been described previously. After a further coronoidectomy with return of function to the temporomandibular joints, a change from a retrognathic mandibular relationship to a gross prognathic position occurred. The management problems encountered with this case are discussed along with a documented account of the treatment provided over a 12-year period. PMID- 8199140 TI - Mechanism of transient mental nerve paraesthesia in sagittal split mandibular ramus osteotomy. AB - We investigated the mechanism involved in paraesthesia associated with sagittal split mandibular ramus osteotomy by three-dimensional computed tomography (3-D CT). Ten female patients underwent this procedure between 1988 and 1991. The inferior alveolar neuro-vascular bundles remained intact during the sagittal osteotomy in all cases. We examined the changes in the shape of the foramen mandibulae over a period of 6 months during which the transient mental nerve paraesthesia was recovered, and studied the distance from the foramen mandibulae to the spina mentalis (F-S distance) as measured on 3-D film. The postoperative 3 D CT scan showed bone resorption in front of the foramen mandibulae, and the F-S distance was shortened by an average of 2.94 mm. These findings suggest that possible causes of the paraesthesia is due to compression of the nerve trunk resulting from posterior movement of the mandibular ramus. PMID- 8199141 TI - The role of angiography in facial trauma: a case report. AB - Angiography is a useful diagnostic tool in maxillofacial trauma. An important indication for its use is in establishing the proximity of foreign objects to the arterial supply to the head and neck. An unusual case of a deeply penetrating knife wound of the face is described to illustrate this point. PMID- 8199142 TI - Merkel cell carcinoma: a clinico-pathological report of 3 cases. AB - Merkel cell carcinomas are rare. The head and neck are the commonest sites of presentation. They are slightly more common in females and are frequently misdiagnosed. This tumour has had little coverage in the surgical journals which accounts for the low index of suspicion. Three cases, which were successfully treated surgically, are presented in order to increase awareness. It is a diagnosis that one should have in mind when examining an atypical skin lesion. PMID- 8199143 TI - A comparison of broad and narrow retractors for lingual nerve protection during lower third molar surgery. AB - The incidence of altered lingual nerve sensation following lower third molar removal was examined in 150 cases where a broad retractor was used to retract the lingual flap and compared with 150 cases where a more conventional Howarth's periosteal elevator was employed. This study supports the view that a broad retractor employed to protect the lingual nerve during lower third molar surgery produces significantly less altered lingual nerve sensation at 1 month than a Howarth's periosteal elevator used for the same purpose. PMID- 8199144 TI - Vacuum requirement in closed surgical drainage of the head and neck. AB - Prophylactic vacuum drainage of surgical wounds is a controversial issue, but is acknowledged to be important in head and neck surgery. A study was undertaken to identify the ideal surgical drain. The results indicate that the low vacuum systems are inefficient, and should not be used in situations where tissue swelling may compromise the airway. PMID- 8199145 TI - Lingual thyroid. AB - A case of lingual thyroid is described. This is unusual in that the entire tongue substance appears to contain thyroid tissue which is revealed graphically in the radioisotope scans. The literature is reviewed regarding the incidence and diagnosis of lingual thyroid with possible treatment options discussed. PMID- 8199146 TI - Lingual nerve retractor. AB - An anatomically designed lingual nerve protector is presented. Its use on two thousand patients and a low incidence of temporary lingual nerve damage is reported. PMID- 8199147 TI - Lateral open bite resulting from acute temporomandibular joint effusion. AB - Two cases of acute open bite, one arising from trauma to the mandible without actual fracture, and one from an acute episode of rheumatoid arthritis, are presented. The resultant malocclusions were due to a sudden increase of volume in the temporomandibular joint space with subsequent displacement of the mandibular condyle, following acute effusion. PMID- 8199148 TI - Intercollegiate examination in oral and maxillofacial surgery. PMID- 8199149 TI - Raw nerves. PMID- 8199150 TI - The shape of the condyle and position of the meniscus in temporomandibular joint dysfunction. AB - The position of the meniscus seems to be significant in the natural history of temporomandibular joint dysfunction. It can be identified on MRI and arthrography but generally its displacement is referred to only in the sagittal plane. Little consideration is given to the shape and size of the condyle which could have great influence upon the position which the meniscus takes up. This paper reports the findings in 105 TM joints which have had arthrotomy for meniscoplasty (meniscopexy) and menisectomy over an 8-year period. Only 30% of the condyles had a normal size and shape; 24% were excavated on the medial side, 15% had lost the anterior surface of the condyle and were oblique in shape, 15% were small and round, while 12.5% were flattened, two having no discernable condyle at all. The meniscus was found to be displaced anteromedially most commonly, with the anterior position, to which reference is so frequently made, being rare; the medial position was more common. The significance of these findings is discussed with particular reference to imaging. PMID- 8199151 TI - The assessment of fracture of the mandibular condyle by use of computerized tomography. Incidence of sagittal split fracture. AB - A survey was carried out to clarify the incidence of sagittal splitting fracture of the mandibular condyle using computerized tomography. There were 33 patients, between 11 and 67 years of age, with displaced or dislocated mandibular condylar process fractures (41 cases), seen at our clinic between 1986 and 1992. The incidence of no displacement was 4.9%; deviation and displacement, 34.1%; dislocation, 46.3%; and complete avulsion, 4.9%. A sagittal splitting fracture of condyle occurred with an incidence of 9.8%. Conservative treatment was effective in the treatment of sagittal splitting fracture. Therefore, classification of fracture of mandibular condyle should include the sagittal split fracture, and investigations should include computerized tomography. PMID- 8199152 TI - Naso-orbital fracture leading to orbital cellulitis, and visual loss as a complication of chronic sinusitis. AB - A case is reported of a 26-year-old man, who after sustaining a fracture involving the nasal complex and left infra-orbital margin developed orbital cellulitis and a sub-periosteal abscess. This resulted in complete loss of vision in that eye. A pre-existing sinusitis was the source of the infection. PMID- 8199153 TI - Use of anorganic bone in periapical defects following apical surgery--a prospective trial. AB - Anorganic bovine bone has been used previously to obturate bony defects following apical surgery with some reported success. However, no prospective trial has been carried out. We present the results of our trial showing that the placement of anorganic bovine bone (BIO-OSS) in defects created by apical surgery is contraindicated. PMID- 8199154 TI - Activity and solubility of bone morphogenetic protein derived from porcine bone matrix. AB - Bone morphogenetic protein (BMP) was extracted from porcine bone matrix and purified by liquid chromatography. The final purified fraction was shown to be homogeneous by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis (SDS-PAGE). The molecular weight of porcine bone matrix-derived BMP was estimated to be about 20 kDa by SDS-PAGE. The final purified BMP was highly soluble in vivo, so that it dispersed immediately after implantation and exerted no effect on bone induction. The other crude active fractions obtained in the process of purification induced new bone in three weeks when implanted into muscle pouches of Wistar rats. These findings suggested that pure BMP requires an appropriate carrier (delivery system) for clinical use; hence, experiments using atelopeptide type-I collagen as carrier were conducted. PMID- 8199155 TI - Adhesion of composite resin to bone--a pilot study. AB - This pilot study investigated the adhesion of composite resin to pig calvarium using All-bond 2 dentine bonding agent in an in vitro model. The bone was subjected to different methods of preparation. Acid-etching decreased the bond strength between bone and composite. Roughening the bone with a surgical bur prior to application of the adhesive produced bond strengths in the range 11.1 16.1 MPa. PMID- 8199156 TI - Disseminated intravascular coagulation presenting as perioral haemorrhage. AB - A case of disseminated intravascular coagulation presenting with lower lip haemorrhage is described. The coagulopathy was secondary to an undiagnosed prostatic adenocarcinoma. The management of such haemorrhage is outlined. PMID- 8199157 TI - Effects of antibiotics on human polymorphonuclear leukocyte chemotaxis in vitro. AB - The effects produced in vitro by minocycline (MINO), aminobenzyl penicillin (ABPC) and cefotiam (CTM) on polymorphonuclear leukocytes (PMN) chemotaxis were investigated in this study using the Boyden chamber technique and polarization assay. The following results were obtained: CTM brought about a significant increase of PMN chemotaxis at the therapeutic dose (10, 100 micrograms/ml), MINO reduced PMN chemotaxis significantly at a concentration as low as 1 microgram/ml and ABPC did not influence PMN chemotaxis at concentrations up to 100 micrograms/ml in both methods. Furthermore, using a checkerboard assay, it was shown that CTM worked as a chemokinetic factor. PMID- 8199158 TI - Predictors of relapse in orthodontically-treated Class III malocclusions. AB - This study aimed to investigate the possibility of predicting relapse from the pretreatment records of children with orthodontically treatable Class III malocclusions. Sixty-four patients were studied: 31 individuals had been treated by a non-extraction technique, the remaining 33 with mid-arch extractions. Cephalometric and model data taken at the start of treatment and at least 2 years after all treatment and retention had ceased were examined. An individual diagnosis of relapse or stability was made from the post-retention records and the start of treatment records analysed in relation to this information. The capacity for predicting the observed outcome of therapy was assessed in three ways: correlation coefficients, the number of cephalometric measurements exceeding two standard deviations from a control group mean, and discriminant analysis. Only the latter proved an effective indicator of relapse, with a separate discriminant model being necessary for each sub-group. PMID- 8199159 TI - Health and safety at work in orthodontic practice. AB - Health and safety is now of major importance in general and specialist dental practice. Risk assessment and management is essential to ensure that practices are healthy and safe for staff, patients and visitors. Practitioners are required to do all that is reasonably practicable to ensure this. At the same time there is also the need to keep practising costs at an economic level. To comply requires a sound working knowledge of the law and regulations. It also involves turning general policies into specific surgery procedures that prevent accidents and promote good practice. Six new sets of regulations on health, safety and welfare were introduced in 1993 in the UK that brings us into step with matching regulations throughout The European Community. The general requirements, the new regulations and their background are discussed in the first of a two part article. Many of the specific problems related to orthodontic practice are discussed in the second article. Many problems can be addressed inexpensively by modifying working practice but this will need to involve the whole dental team. PMID- 8199160 TI - A comparison of the frictional characteristics of five initial alignment wires and stainless steel brackets at three bracket to wire angulations--an in vitro study. AB - The study investigated static planar frictional resistance between five initial alignment wires and stainless steel brackets at three bracket to wire angulations (0, 5 and 10 degrees). It was demonstrated that static frictional resistance increased significantly with increasing bracket to wire angulation due to binding within the system. Epoxy-coated steel had the highest static frictional resistance and coaxial stainless steel the lowest. Fibre-optic glass (Optiflex) had low frictional resistance. The coefficient of friction followed the trends of static frictional resistance in all respects. PMID- 8199161 TI - L(+)-lactic acid production in plaque from orthodontic appliances retained with glass ionomer cement. AB - The lactic acid production in suspensions of plaque collected adjacent to orthodontic brackets retained with a glass ionomer cement (GIC), or a resin-based composite was investigated using a split-mouth technique. Forty-eight-hour-old plaque was collected at 3, 8, and 28 days, and 3 months after the onset of orthodontic treatment. Acid fermentation was induced by glucose and the L(+) lactic acid concentrations were determined enzymatically after a 30-minute incubation period. Significantly (P < 0.05) lower levels of lactic acid were found in plaque from GIC-retained brackets compared with the composite controls at the 28 days and 3 months sampling occasions, respectively. The results suggest that the use of GIC as a bonding agent in orthodontics can be beneficial for patients assessed at risk of caries development. PMID- 8199162 TI - A laboratory investigation into cements used to retain orthodontic bands. AB - A laboratory study is presented where a technique of band retention testing is characterized. A glass polyalkenoate and a zinc phosphate cement were evaluated for band retention under simulated conditions of mechanical stress. In the absence of mechanical and other stresses there was no difference in the two cements for band retention. However, after mechanical stress was applied the glass polyalkenoate cement proved superior to the zinc polyalkenoate cement for band retention (P < 0.05). Weibull analysis is presented and described as a useful adjunct to statistical handling of band retention data. PMID- 8199163 TI - A critique of bond strength testing in orthodontics. AB - The literature contains a large number of publications on in vitro bond strength testing of materials used in orthodontics. The results are often quoted by manufacturers to support their products. Little attention has been paid to the detail of the test procedures used. However, a review of the literature revealed a large variation in the methods used for bond strength testing in orthodontics making comparison of papers difficult and often impossible. The case for a possible standard technique is suggested. It is hoped that this will lead to more meaningful testing of new products, which will produce more reliable guidance for the clinical orthodontist. PMID- 8199164 TI - Quality assessment of lateral cephalograms amongst radiologists and orthodontists. AB - This study investigated technical errors in the production of lateral cephalograms necessitating a retake and the extent to which the retake, as ordered by the radiologist, actually produced a gain in quality as assessed by the orthodontist. All the rejected lateral cephalograms taken at the Department of Oral Radiology over a period of 1 year were saved, and 20 such radiographs and their approved counterparts were then studied. Ten orthodontists were asked to decide whether the radiographs were acceptable or not and to provide reasons for those judged unacceptable. Considerable variation was found between the 10 orthodontists in the rate of acceptance of the radiographs. One orthodontist accepted only 13, while another accepted 37 out of the 40 radiographs. The main cause for rejection by the orthodontists of the radiologically approved films was: patients positioning error, and for the rejected: poor (or no) intercuspation. The results show large discrepancies between the radiologists and the orthodontists in quality criteria for cephalometric radiographs, as well as large interindividual variations among the orthodontists. In half of the cases, the radiologists ordered retakes that, according to the orthodontists, were not necessary. PMID- 8199165 TI - The role of inter-canine width in late lower arch crowding. PMID- 8199166 TI - The prevalence of malocclusion amongst Hong Kong male dental students. AB - The prevalence of malocclusion and treatment need amongst young Chinese adults has not previously been documented in Hong Kong. One-hundred-and-eight Chinese male first year dental students were assessed using the Occlusal Index. It was found that 41.7 per cent of the 108 needed orthodontic treatment and 24.1 per cent needed comprehensive orthodontic treatment to correct major malocclusions. The most commonly occurring feature was crowding (38.9 per cent), followed by Class II malocclusion (21.3 per cent), and Class III malocclusion (14.8 per cent). PMID- 8199167 TI - Dentists variation in the determination of orthodontic treatment need. AB - The criteria that dentists use to judge the need for orthodontic treatment are not clear. This study investigates variation in dentists' perception of orthodontic treatment need. Seventy-four dentists were asked to assess 320 dental casts in relation to aesthetic and dental health need. The results of this investigation revealed that the panel was divided as what constituted a need for orthodontic treatment on dental health grounds. It is suggested that one method of achieving a more uniform evaluation of orthodontic treatment need is the use of an occlusal index. Until an occlusal index is accepted and used by the profession, the distortion of need and demand for orthodontic treatment by dentists' unequal perceptions will continue. PMID- 8199168 TI - A report of orthodontic undergraduate education in two dental schools: Toronto, Canada and Liverpool, England. AB - The undergraduate orthodontic courses at Toronto and Liverpool are compared. Each course comprises more than 250 hours of teaching and within that, more than 100 hours involve clinical tuition. Both courses contain laboratory modules for the teaching of removable and fixed appliance technique. Undergraduates treat their own patients with both simple and complex appliances, within their clinical training period which extends over at least 2 years. Liverpool undergraduates treat more patients per student than their counterparts in Toronto (P < 0.05). During the third year of study, the clinical experience of the Liverpool students (P < 0.001) is made up of a greater proportion of patients treated with removable appliances. In both centres, senior students treat patients with a greater preponderance of fixed appliance techniques and two-arch treatments. PMID- 8199169 TI - Academic staff who have resigned their university posts: an Association of University Teachers of Orthodontics (AUTO) report. PMID- 8199170 TI - Orthodontic bonding adhesives. PMID- 8199171 TI - Oral health gain for Wales--the orthodontic contribution. PMID- 8199172 TI - Induction of LDL receptor-related protein during the differentiation of monocyte macrophages. Possible involvement in the atherosclerotic process. AB - The low-density lipoprotein receptor-related protein (LRP) is a multifunctional receptor that binds to apolipoprotein E-rich lipoproteins, lipoprotein lipase, alpha 2-macroglobulin, lactoferrin, and tissue plasminogen activator. We studied the mRNA expression of LRP in human monocyte-derived macrophages and THP-1 cells. mRNA expression of LRP was induced during cell differentiation from human monocytes to macrophages or after incubation with phorbol ester (tetradecanoylphorbol acetate 100 ng/mL) in THP-1 cells, and the addition of 30 ng/mL macrophage colony-stimulating factor further enhanced LRP expression. These results indicated that the expression of LRP depended on the stage of differentiation and maturation of monocytic cells. mRNA expression of LRP was also enhanced in human monocyte-derived macrophages in the presence of acetylated low-density lipoprotein and in aorta of rabbits fed a high-cholesterol diet. We hypothesize that the LRP induced in monocyte-derived macrophages is involved in the initial process of atherosclerosis by interacting with its multiple ligands. PMID- 8199173 TI - Chylomicron-induced prothrombin activation and platelet aggregation. AB - The effects on platelet aggregation of native rat chyle chylomicrons, chylomicron remnants, and chylomicrons that had been preincubated with rat or human EDTA plasma, serum, whole blood, or pure human prothrombin were examined. The native chyle chylomicrons did not induce platelet aggregation but decreased ADP- and thrombin-induced platelet aggregation and [14C]serotonin release. Chylomicron remnants also failed to induce platelet aggregation, but they potentiated the aggregation and the [14C]serotonin release induced by ADP and thrombin. Aggregation, after a lag phase of 15 to 20 minutes, was seen when platelets were incubated with chylomicrons that had been preincubated with plasma and then isolated as the top layer after a single centrifugation at d = 1.006. This aggregation was inhibited in a dose-dependent manner by an antiserum against prothrombin that also inhibited thrombin-induced platelet aggregation. After washing by centrifugation the plasma-preincubated chylomicrons did not induce platelet aggregation, but this effect could be restored by adding a small amount of prothrombin, which did not cause aggregation when added alone or together with native chyle chylomicrons. Addition of 2% (vol/vol) plasma, however, induced aggregation when added together with either native chyle chylomicrons or washed preincubated chylomicrons, but not when added alone. Binding of 125I-labeled prothrombin to native chyle chylomicrons was demonstrated by gradient ultracentrifugation. During incubation of washed plasma-preincubated chylomicrons with 125I-prothrombin and platelets, a significant conversion of 125I-prothrombin to 125I-prethrombin and 125I-thrombin occurred, as demonstrated by autoradiography after separation on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The interaction between chylomicrons and prothrombin, and possibly other coagulation proteins, thus enhances prothrombin activation in the presence of platelets. PMID- 8199174 TI - Serum ferritin, sex hormones, and cardiovascular risk factors in healthy women. AB - The protective effect of endogenous sex hormones is commonly believed to explain the gender gap in the risk of coronary heart disease and the diminished protection in women when menopause occurs. Recent reports indicate that iron overload, due to cessation of menstrual bleeding, may be an important factor. We therefore investigated iron stores by serum ferritin measurements in healthy premenopausal (n = 113) and postmenopausal (n = 46) women. Ferritin levels were higher in postmenopausal than in premenopausal women, both in blood donors (43.4 versus 23.1 micrograms/L, P < .001) and in nondonors (71.7 versus 32.8 micrograms/L, P < .001). Serum ferritin was positively correlated with age (r = .36, P < .001). After age adjustment, serum ferritin was positively correlated with hemoglobin, hematocrit, serum total cholesterol, and low-density lipoprotein (LDL) cholesterol. Total cholesterol was correlated with age (r = .66, P < .001), as were LDL cholesterol (r = .60, P < .01) and high-density lipoprotein cholesterol (r = .32, P < .01). Neither ferritin nor serum lipids were directly associated with female sex hormone levels. The mutual relation between ferritin, hemoglobin, and hematocrit probably only indicates their usefulness as measures of body iron. The parallel rise in serum ferritin, total cholesterol, and LDL cholesterol might contribute to the increased risk of coronary heart disease among postmenopausal women. PMID- 8199175 TI - Sex differences in susceptibility to etiologic factors for peripheral atherosclerosis. Importance of plasma fibrinogen and blood viscosity. AB - Cardiovascular risk factors in men, such as cigarette smoking, hypercholesterolemia, and hypertension, also increase risk in women, but the relative susceptibility to risk factors between the sexes is not established. Our aim was to investigate a wide range of possible etiologic factors in a single population study and identify those that were more strongly related to peripheral atherosclerosis in men or women. We studied personal factors (age and social class), lifestyle factors (smoking, exercise, alcohol intake, and dietary nutrients), and intermediary factors (obesity, diabetes, serum lipids, coagulation, and rheological factors). In the Edinburgh Artery Study in 1988 we measured cardiovascular risk factors in a random population sample of 1592 men and women aged 55 to 74 years. The ankle-brachial pressure index (ABPI), which is inversely related to the degree of peripheral atherosclerosis, was assessed in each subject. Lifetime cigarette smoking was correlated with a lower ABPI equally in men and women (r = -.27, P < .001). Dietary nutrients and alcohol intake were not related differently between the sexes with ABPI. However, recall of strenuous and moderate leisure time exercise during the age range of 35 to 45 years was related more strongly to a higher ABPI in men than in women (P < .05). Plasma fibrinogen, plasma viscosity, and blood viscosity were the only intermediary factors that had stronger univariate correlations with lower ABPI in men than in women. On multivariate analysis, the sex differences persisted for plasma fibrinogen (P < .05) and blood viscosity (P < .001); high-density lipoprotein cholesterol was related to ABPI in men only (sex difference, P < .1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199176 TI - The LPL gene in individuals with familial combined hyperlipidemia and decreased LPL activity. AB - Familial combined hyperlipidemia (FCHL) is an oligogenic disorder, with family members having elevated apolipoprotein B-100 levels and either elevated plasma cholesterol or triglyceride levels or both. Obligate heterozygous parents of children with lipoprotein lipase (LPL) deficiency express a mild FCHL phenotype. Of patients with FCHL, 36% have diminished postheparin LPL activity and mass values that are comparable with those of obligate heterozygotes for LPL deficiency. It is hypothesized that heterozygosity for mutations in the LPL gene could contribute to FCHL in this subset of patients. Single-strand conformation polymorphism (SSCP) analysis, direct DNA sequencing, and Southern blot analysis were used to examine exons 1 through 9 and exon-intron junctions of the LPL gene in 20 patients with FCHL and low LPL activity and mass. One subject had a substitution (GAC-->AAC) in exon 2, changing Asp9 to Asn. Two subjects had a previously undescribed "silent" substitution (GTG-->GTA) in exon 3 at Val108. Three patients had a premature termination at codon 447 in exon 9 resulting in truncation of the mature protein by two amino acids. In addition to SSCP analysis, exons 4, 5, and 6, where almost all mutations in LPL-deficient patients have been found, were sequenced and no additional mutations were found. Southern blot analysis of the LPL gene revealed one subject with heterozygous loss of an EcoRI site but without an abnormality in Stu I restriction fragments; this mutation is therefore unlikely to be functionally significant. The substitutions identified at codons 9 and 447 have previously been found not to affect lipolytic activity when expressed in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199177 TI - Associations of allelic differences at the A-I/C-III/A-IV gene cluster with carotid artery intima-media thickness and plasma lipid transport in hypercholesterolemic-hypertriglyceridemic humans. AB - Individuals with elevated levels of plasma cholesterol and triglyceride may be at higher risk for coronary artery disease than those with isolated elevations of either cholesterol or triglyceride. Sequence variation in the A-I/C-III/A-IV gene cluster has been implicated in the etiology of some disorders associated with premature atherosclerosis and/or hypertriglyceridemias with or without elevations of cholesterol. This led to the hypothesis that allelic variation at this gene locus alters plasma lipid transport and affects susceptibility for atherosclerosis. The study population, from the Atherosclerosis Risk in Communities (ARIC) Study, consisted of 50 normolipidemic individuals, 48 subjects with elevated plasma cholesterol, 47 subjects with elevated plasma triglyceride, and 123 subjects with both elevated plasma cholesterol and triglyceride who were used to evaluate associations between an Xmn I polymorphic site 2.5 kilobase pairs (kbp) upstream of the structural gene for apolipoprotein (apo) A-I, intimal medial thickening of the extracranial carotid arteries, and several plasma lipid factors. The relative allele frequencies of the 8.3-kbp allele and the 6.6-kbp allele were .86 and .14, respectively, in the entire study population and did not differ among the lipid phenotypes. In the group with elevated plasma cholesterol and triglyceride, subjects possessing the 6.6-kbp allele exhibited a greater carotid artery intimal-medial thickness (P = .034) and higher plasma levels of apoA-I, high-density lipoprotein (HDL) cholesterol, and HDL3 cholesterol (P < .02) than subjects homozygous for the 8.3-kbp allele. In contrast, subjects with the 6.6-kbp allele displayed lower mean ratios of apolipoproteins C-II to C-III, C-II to A-IV and E to A-IV in plasma (P < .05) and a lower mean ratio of apolipoprotein C-II to C-III in the triglyceride-rich lipoproteins (P = .026). Sequence variation in or near the genes encoding apolipoproteins A-I, C-III, and A-IV may therefore identify a group of hypercholesterolemic-hypertriglyceridemic persons who are at higher risk for atherosclerosis than others with the same lipoprotein phenotype. PMID- 8199178 TI - ApoA-IV phenotype affects diet-induced plasma LDL cholesterol lowering. AB - The National Cholesterol Education Program (NCEP) recommends that dietary total fat, saturated fat, and cholesterol intake be reduced to < or = 30% of calories, < 10% of calories, and < 300 mg/d, respectively (step 1 diet), in the general population to reduce plasma low-density lipoprotein cholesterol (LDL-C) levels and heart disease risk. We examined the LDL-C-lowering response to such a diet (26% fat, 8% saturated fat, and 201 mg/d cholesterol) compared with an average American diet (39% fat, 15% saturated fat, and 435 mg cholesterol/d) in 153 subjects using diet periods of 4 through 24 weeks for each diet phase. The mean LDL-C reduction was 13% in men (n = 93) and 7% in postmenopausal women (n = 60). The effect of apolipoprotein (apo) A-IV phenotype on responsiveness was examined. LDL-C lowering in men was significantly (P < .005) less (7%) for 17 apoA-IV (1/2) subjects than for 76 apoA-IV (1/1) subjects (16%). In women, 7% lowering was observed in both 12 apoA-IV (1/2) subjects and 48 apoA-IV (1/1) subjects. ApoA-IV phenotype had a significant effect on plasma high-density lipoprotein cholesterol levels during both dietary periods; women carrying the apoA-IV-2 allele had higher levels than those homozygous for the apoA-IV-1 allele. The opposite was true for triglyceride levels, but only during the period when the subjects consumed the high-fat, high-cholesterol diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199179 TI - Effects of increasing dietary polyunsaturated fatty acids within the guidelines of the AHA step 1 diet on plasma lipid and lipoprotein levels in normal males. AB - We attempted to ascertain the effects of polyunsaturated fatty acids by conducting two studies in normal young men, in which monounsaturated fats were replaced by polyunsaturated fats within the guidelines of the American Heart Association step 1 diet. Study A employed a randomized parallel design in which subjects first consumed an average American diet (AAD) containing 37% of calories as fat (saturated fat, 16% calories; monounsaturated fat, 14% calories; and polyunsaturated fat, 7% calories). After 3 weeks, one third of the subjects continued with the AAD, one third switched to a step 1 diet in which total fat calories were reduced to 30% by replacing saturated fat with carbohydrate, and one third switched to a polyunsaturated fat-enriched (Poly) diet with the same 30% fat calories and a reduction of monounsaturated fat from 14% to 8% and an increase of polyunsaturated fat from 7% to 13% of calories. The randomized period lasted 6 weeks. Total and low-density lipoprotein (LDL) cholesterol levels on the step 1 and Poly diets were reduced compared with levels on the AAD (P < .001). Total and LDL cholesterol did not differ between the step 1 and Poly diets, although comparison between the two diets is limited by the small study groups. Serum apolipoprotein (apo) B levels fell on the Poly diet compared with the AAD. Total high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol levels were not significantly affected by the diets. Postprandial lipid and lipoprotein concentrations did not significantly differ either. In study B, a randomized crossover design was used in which all subjects ate the step 1 and Poly diets for 5 weeks each with a 4-day break between diets. In the eight subjects studied, the values for fasting plasma total, LDL, and HDL cholesterol; triglycerides; apoB; and apoA-I were essentially identical at the end of each diet period. Postprandial triglyceride areas obtained after ingestion of a large, standard fat load were also the same. Finally, LDL apoB and HDL apoA-I turnovers were unaffected by replacement of monounsaturates with polyunsaturates. In summary our results indicate that modest exchanges of monounsaturated for polyunsaturated fats do not significantly affect LDL or HDL levels or metabolism, which supports the view that reducing saturated fats is the key to lowering total and LDL cholesterol. PMID- 8199180 TI - Determinants of LDL subfraction distribution and concentrations in young normolipidemic subjects. AB - Human low-density lipoproteins (LDLs) comprise a spectrum of particles that vary in size, density, chemical composition, metabolic behavior, and atherogenicity. To identify determinants of this heterogeneity, we measured the percent distribution and plasma concentration of the three major LDL subfractions in 34 young healthy subjects. These parameters were correlated in univariate and multivariate analyses with various body and lifestyle factors; plasma lipids and lipoprotein; and the activities of cholesteryl ester transfer protein, lipoprotein lipase, and hepatic lipase (HL). Women (n = 15) had significantly more large, buoyant LDL (LDL-I; density, 1.025 to 1.034 g/mL) and high-density lipoprotein2 (HDL2) than men (n = 19). Both the percentage and concentration of LDL-I were correlated negatively with very-low-density lipoprotein triglycerides (VLDL-TG) and HL; they were correlated positively with HDL-cholesterol (HDL-C) and HDL2. In addition, percent LDL-I was negatively correlated with plasma triglycerides, VLDL-C, LDL-C, and apo-lipoprotein (apo) B concentrations. The concentrations of intermediate and small, dense LDL (LDL-II and LDL-III; density, 1.034 to 1.044 and 1.044 to 1.060 g/L, respectively) were positively correlated with LDL-C. LDL-III concentrations were also related to plasma cholesterol and apoB concentrations and HL activity. On multivariate analyses, approximately one third of the variability in LDL-I was explained by HL and plasma triglycerides. More than 80% of the variation in LDL-II was accounted for by a model that combined LDL-C and plasma apoB with body mass index and VLDL-TG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199181 TI - Lipoprotein abnormalities in non-insulin-dependent diabetic patients with impaired extrahepatic insulin sensitivity, hypertension, and microalbuminuria. AB - We investigated whether specific lipoprotein abnormalities are present in non insulin-dependent diabetes mellitus (NIDDM) patients with hypertension and/or microalbuminuria. Fifteen normotensive normoalbuminuric (H-M-), 32 hypertensive normoalbuminuric (H+M-), and 22 hypertensive microalbuminuric (H+M+) NIDDM patients and 20 sex-, age-, and weight-matched nondiabetic control subjects were studied. Lipoprotein size was measured by nondenaturing polyacrylamide gradient gel electrophoresis; insulin sensitivity was assessed by using a euglycemic hyperinsulinemic clamp and [6,6(2)H]glucose tracer infusion for simultaneous measurement of hepatic glucose output and whole-body glucose utilization. Total plasma and very-low-density lipoprotein cholesterol were higher in H+M+ than in control subjects (5.84 +/- 0.98 versus 4.97 +/- 0.98 and 0.57 +/- 0.54 versus 0.26 +/- 0.21 mmol/L, mean +/- SD, P < .05). Plasma triglycerides were higher in H+M+ than in either control or H-M- subjects (2.17 +/- 1.32 versus 1.18 +/- 0.67 and 1.30 +/- 0.59 mmol/L, respectively; P < .05). The mean low-density lipoprotein diameter was 27.2 +/- 0.8 in control, 26.7 +/- 0.8 in H-M-, 26.5 +/- 0.8 nm in H+M- (P < .05 versus control subjects), and 26.0 +/- 0.8 nm in H+M+ subjects (P < .05 versus control subjects). The mean cholesterol level of the large high-density lipoprotein particles was lower in H+M- and H+M+ (0.37 +/- 0.14 and 0.36 +/- 0.16 mmol/L) than in control and H-M- (0.54 +/- 0.41 and 0.54 +/- 0.27 mmol/L, P < .05) subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199182 TI - Resistance to insulin-stimulated glucose uptake and dyslipidemia in Asian Indians. AB - Persons from the Indian subcontinent have elevated coronary heart disease risk. We measured insulin resistance with the insulin suppression test in 22 Asian Indian men and women and an equal number of control subjects of European ancestry matched for age and body mass index. Asian men and women had increased glucose and insulin responses to oral glucose tolerance tests (P < .05 by ANOVA) and had approximately 60% higher steady-state plasma glucose levels during the insulin suppression test (P < .001 by ANOVA), consistent with insulin resistance. In response to mixed meals, Asian women had higher plasma free fatty acids and glycerol concentrations than women of European ancestry (P < .02 by ANOVA), whereas Asian Indian men had similar free fatty acid and glycerol levels compared with men of European ancestry despite higher plasma insulin levels. Thus, results in both sexes were consistent with resistance to insulin suppression of free fatty acid levels in Asian Indians. Asian Indians of both sexes had higher fasting plasma triglyceride (P < .01) and lower high-density lipoprotein cholesterol (P < .01) concentrations than men and women of European ancestry. Resistance to insulin-stimulated glucose uptake and to insulin suppression of free fatty acid levels in Asian Indians is associated with a number of metabolic abnormalities that are demonstrated risk factors for coronary heart disease, including increased glucose, insulin, and triglyceride concentrations and decreased high-density lipoprotein cholesterol concentrations. PMID- 8199183 TI - Familial and diet-induced hypercholesterolemia in swine. Lipid, ApoB, and ApoA-I concentrations and distributions in plasma and lipoprotein subfractions. AB - Low levels of high-density lipoproteins (HDLs) may constitute an independent risk factor that may be as important as elevated low-density lipoproteins (LDLs) in coronary artery disease (CAD). Concentrations and distributions of lipids, apolipoprotein (apo) B, and apoA-I in the plasma and lipoprotein subfractions of two groups of swine, one with familial hypercholesterolemia (FHC) and the other with diet-induced hypercholesterolemia (DHC), were examined. Normolipidemic (NL) animals served as controls. All pigs carried the Lpb5 apoB mutation, which is known to influence the formation of atherosclerotic lesions. Mean concentrations of serum total cholesterol in NL, DHC, and FHC were 80.0 +/- 9.3, 774.3 +/- 54.5, and 316.5 +/- 36.1 mg/dL, respectively; HDL cholesterol (HDL-C), 33.5 +/- 1.9, 137.0 +/- 9.9, and 22.3 +/- 2.2 mg/dL; triglycerides, 33.0 +/- 16.3, 40.3 +/- 11.7, and 56.8 +/- 7.2 mg/dL; apoB, 35.7 +/- 3.1, 142.0 +/- 4.8, and 169.3 +/- 13.9 mg/dL; and apoA-I, 62.4 +/- 9.3, 170.9 +/- 6.9, and 42.6 +/- 4.8 mg/dL. The distributions of total cholesterol, apoB, and apoA-I in plasma lipoprotein subfractions were also examined. Compared with NL, FHC had fourfold and 4.7-fold increases in total cholesterol and apoB, respectively, distributed in the lower densities (d < 1.043 g/mL), and low HDL-C and apoA-I levels, resulting in a high total cholesterol/HDL-C ratio (14.4:1) and elevated triglyceride levels. DHC was characterized by 10-fold and fourfold increases in total cholesterol and apoB, respectively, resulting in an LDL particle highly enriched in cholesterol, a fourfold increase of HDL-C, an almost threefold increase in apoA-I, and a normal triglyceride level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199184 TI - Cell compositions of coronary and aortic atherosclerotic lesions in WHHL rabbits differ. An immunohistochemical study. AB - This study investigated whether coronary atherosclerosis was different from aortic atherosclerosis in Watanabe heritable hyperlipidemic rabbits. Atherosclerotic lesions were immunohistochemically stained by using a monoclonal antibody for rabbit macrophages (RAM-11) and a monoclonal antibody for muscle actin (HHF35) and were also subjected to conventional staining. The areas of the major lesional components, ie, macrophages, smooth muscle cells, collagen fibers, and extracellular lipid deposits, were measured with a color image analyzer. The percent macrophage area in coronary lesions was significantly lower compared with aortic lesions at all stages (early fatty streak, transitional, and advanced), while the percent smooth muscle cell area and collagen area were significantly higher in early fatty streak lesions of the coronary arteries. In addition, the macrophage area/smooth muscle cell area ratio was significantly lower in coronary lesions compared with aortic lesions at all stages. In conclusion, coronary atherosclerosis had a small number of macrophages and was rich in smooth muscle cells, whereas aortic atherosclerosis showed the opposite features. These results suggested that the role of macrophages and smooth muscle cells in the initiation and/or progression of coronary atherosclerosis differs from the role of these cells in aortic atherosclerosis. PMID- 8199185 TI - L-arginine improves endothelium-dependent vasorelaxation and reduces intimal hyperplasia after balloon angioplasty. AB - Reductions in nitric oxide (NO) activity persist after arterial intimal injury and may be a factor in the development of intimal hyperplasia. NO inhibits in vitro platelet aggregation, leukocyte adhesion, and smooth muscle cell growth, all of which are key components in the process of intimal hyperplasia. We hypothesized that long-term supplementation with L-arginine, the precursor of NO, would increase NO production and thereby improve endothelium-dependent vasorelaxation and simultaneously reduce intimal hyperplasia. Twenty-six New Zealand White male rabbits were fed standard rabbit chow either with or without 2.25% L-arginine in their drinking water for 3 weeks. Then the animals underwent unilateral iliac artery angioplasty and were continued on their respective diets. Four weeks after angioplasty, the iliac arteries were harvested for functional and morphometric studies. The iliac arteries from several animals from each group were processed for study by electron microscopy. Maximal endothelium-dependent vasorelaxation in injured arteries was significantly greater in L-arginine supplemented animals (mean +/- SEM, 71.8 +/- 4.1%; n = 6) than controls (51.4 +/- 4.0%, n = 7; P < .05). Furthermore, the intimal area in injured arteries was significantly reduced in L-arginine-supplemented animals (0.22 +/- 0.03 mm2, n = 5) compared with controls (0.34 +/- 0.03 mm2, n = 6; P < .05). These data suggest that L-arginine supplementation enhances NO production at sites of vascular healing and may reduce intimal hyperplasia. PMID- 8199186 TI - Cyclosporin suppresses transplant arteriosclerosis in the aorta-allografted, cholesterol-clamped rabbit. Suppression preceded by decrease in arterial lipoprotein permeability. AB - The immunosuppressant cyclosporin has been suggested to aggravate as well as retard the development of transplant arteriosclerosis, the major long-term problem for patients with heart transplants. We examined the effect of human therapeutic levels of blood cyclosporin on the development of experimental transplant arteriosclerosis. The thoracic aorta from one rabbit was transplanted as an end-to-side bypass on the abdominal aorta of another rabbit, and plasma cholesterol was clamped at 5 to 7 mmol/L. Cyclosporin markedly suppressed the severity of transplant arteriosclerosis, judged both biochemically and histologically: cholesterol content in aortic transplants was reduced by 70% and 80% after 10 days and 20 days of cholesterol feeding, respectively (both comparisons, P < .01), and after 20 days of cholesterol feeding myointimal proliferation was totally inhibited in grafts from cyclosporin-treated animals, judged from maximal intimal thickness and intimal area on cross sections of grafts (both comparisons, P < .05). In another group of non-cholesterol-fed, aorta-transplanted rabbits, cyclosporin reduced by 90% (P < .01) an otherwise markedly increased permeability to low-density lipoprotein in transplanted aortas. These results suggest that cyclosporin causes a substantial decrease in the severity of transplant arteriosclerosis and that this effect is mediated at least partly via a large decrease in aortic lipoprotein permeability. PMID- 8199187 TI - Enhanced coronary vasoconstrictive response to serotonin subsides after removal of dietary cholesterol in atherosclerotic monkeys. AB - Constriction in response to serotonin is enhanced in the coronary arteries of atherosclerotic monkeys. The main objective of the present study was to determine whether abnormal responses to serotonin in atherosclerosis are reversed following removal of dietary cholesterol. In addition, we examined the effect of an atherogenic diet and reduction in dietary cholesterol on vascular responses to activation of ATP-sensitive K+ channels with aprikalim. Diameters of small coronary arteries were measured on the epicardial surface of the left ventricle in vivo by using stroboscopic illumination synchronized to the heart cycle to visually freeze the motion of the heart. Diameters were measured with a microscope-video system during topical application of two vasoconstrictor agonists, serotonin and the thromboxane mimetic U46619, and the vasodilator agonists aprikalim and nitroprusside. Responses were compared in normal (n = 9), atherosclerotic (n = 14; high-cholesterol diet), and regression (n = 8; high cholesterol diet followed by normal diet) monkeys. Constriction of coronary arteries in response to serotonin was enhanced in monkeys on an atherogenic diet and was normal in regression monkeys. Vasoconstriction in response to U46619 and vasodilation in response to nitroprusside and aprikalim were not altered by atherosclerosis. Thus, abnormal vascular responses to serotonin in small coronary arteries of atherosclerotic monkeys without morphological evidence of disease can be reversed to normal by reducing dietary cholesterol. PMID- 8199188 TI - Long-term induction and regression of diet-induced atherosclerotic lesions in rhesus monkeys. I. Morphological and chemical evidence for regression of lesions in the aorta and carotid and peripheral arteries. AB - Atherosclerotic lesions were induced in rhesus monkeys by feeding a high saturated fatty acid and high-cholesterol diet. After 5.4 years the extent of fatty streaks and raised lesions was evaluated in one group of animals (group P) by visual estimation in 10 arterial segments and chemically in four arterial segments. The remaining animals were switched to a basal regression diet low in cholesterol but high in saturated fatty acids for up to 3.7 years. Regression of lesions was evaluated in one group for 1.9 years (group R4) and in another for 3.7 years (group R5) after deleting cholesterol from the diet. The atherogenic diet increased serum cholesterol levels in all animals from a mean of 150 mg/dL to a mean of about 430 mg/dL. The atherogenic diet produced lesions in group P in all arterial segments (involving up to 50% of the arterial intimal surface) and increased cholesterol content in four arterial segments (varying between 443 and 506 micrograms/cm2). Switching to the basal regression diet decreased serum cholesterol levels to normal after 12 to 18 weeks. The switch to the basal diet significantly decreased the extent of fatty streaks in most arterial segments in both groups. Although differences in the mean extent of raised lesions among groups were not statistically significant, 7 of 10 arterial segments in group R4 and 9 of 10 segments in group R5 showed a lesser extent of raised lesions than in group P. Cholesterol content was lower (P < .05) in all four arterial segments in group R5 than in group P.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199189 TI - Protein tyrosine kinase inhibitors inhibit chemotaxis of vascular smooth muscle cells. AB - The effects of protein tyrosine kinase inhibitors on platelet-derived growth factor (PDGF)-induced chemotaxis in cultured rat aortic smooth muscle cells (SMCs) were investigated to elucidate the role of tyrosine phosphorylation in the chemotaxis of vascular SMCs. Two tyrosine kinase inhibitors, methyl 2,5 dihydroxycinnamate and genistein, inhibited PDGF-induced chemotaxis, the IC50 being 5 and 150 mumol/L, respectively. Methyl cinnamate and genistein partly inhibited the adhesion of SMC to collagen-coated dishes. A chemotaxis assay using double-well culture dishes revealed that both agents also inhibited cell migration after adhesion. H-7, a C kinase inhibitor, did not inhibit either chemotaxis or SMC adhesion at 100 mumol/L. Western blot analysis using anti phosphotyrosine revealed that the tyrosine kinase inhibitors inhibited the tyrosine phosphorylation of at least two proteins of molecular weight 85 and 95 kD under our experimental conditions. An immunocytochemical study revealed that these inhibitors eliminated tyrosine phosphorylation along the cell margins; these agents also inhibited the reorganization of microtubules and stress fibers, both of which are involved in directional cell locomotion. These findings suggest that tyrosine kinases may play an important role in SMC chemotaxis. PMID- 8199190 TI - Rat aortic smooth muscle cells isolated from different layers and at different times after endothelial denudation show distinct biological features in vitro. AB - Endothelial denudation by balloon injury of the rat aorta induces the development of a neointima as a consequence of the migration and proliferation of smooth muscle cells (SMCs). Initially, intimal SMCs show a dedifferentiated phenotype, which reverts to a normal differentiated phenotype after endothelial cells have resurfaced the vessel lumen. We investigated in vitro the proliferative and phenotypic features of SMCs from different layers of rat aorta isolated 15 and 60 days after endothelial denudation. Freshly isolated intimal cells 15 days after balloon injury (IT-15) appeared rounded and showed a decreased content of alpha smooth muscle actin, smooth muscle myosin, and desmin compared with intimal cells isolated 60 days after balloon injury (IT-60). No morphological and cytoskeletal differences were observed among freshly isolated IT-60 cells and other medial populations, which included medial SMCs that underlie the intimal thickening. In culture, IT-15 cells showed increased proliferative activity both in monolayers and in free-floating collagen lattices. Decreased expression of alpha-smooth muscle actin and smooth muscle myosin was documented in IT-15 cells compared with IT-60 cells and other medial SMC populations in monolayer. Moreover, IT-15 cells suspended in collagen lattices were poor at contracting these collagen lattices compared with IT-60 and control SMCs. IT-60 cells were equivalent to control SMCs at lattice contraction except for a temporary delay at day 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199191 TI - Morphological alterations in endothelial cells associated with the release of von Willebrand factor after thrombin generation in vivo. AB - von Willebrand factor (vWF) is synthesized by endothelial cells and stored in endothelium-specific granules, the Weibel-Palade (WP) bodies. The release of vWF from endothelial cells in vitro in response to secretagogues such as thrombin is considered to result in the loss of WP bodies through the fusion of the WP bodies with the plasma membrane. Biochemical and morphological techniques, including transmission (TEM) and scanning (SEM) electron microscopy, were used to examine the plasma profile of vWF in parallel with morphological alterations in endothelial cells associated with the generation of thrombin in vivo. There was a rapid loss of high-molecular-weight multimers of the circulating vWF, with full recovery within 1 hour. Simultaneously, TEM demonstrated that the endothelial cells lost WP bodies and became severely vacuolated; this was associated with the appearance of craters in the endothelial surface on SEM. Release of stored vWF in WP bodies seemed to follow the fusion of multiple rather than individual WP bodies, with the resulting vacuole fusing and rupturing through the plasmatic membrane. Within 1 hour there was increased morphological evidence of metabolic organelle activity associated with replacement of WP bodies, presumably due to de novo synthesis of the basic protomer and its packaging in high-molecular-weight multimeric form in the storage organelles. PMID- 8199192 TI - Tumor metastasis formation: cell-surface proteins confer metastasis-promoting or suppressing properties. PMID- 8199193 TI - Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. AB - It has been realized that the loss of epithelial differentiation in carcinomas, which is accompanied by higher mobility and invasiveness of the tumor cells, is often a consequence of reduced intercellular adhesion. A variety of recent reports have indicated that the primary cause for the 'scattering' of the cells in invasive carcinomas is a disturbance of the integrity of intercellular junctions, often involving loss of a functional cell-cell adhesion molecule E cadherin. It has also been suggested that during invasion, carcinoma cells convert to a sort of mesenchymal stage, as do normal epithelial cells during development. In the present review, permanent and transient molecular mechanisms are discussed which lead to the impairment of junction integrity of the epithelial cells and thus to the progression of carcinomas towards a more metastatic state. Furthermore, the now extensive literature on the down regulation of E-cadherin expression in human and animal carcinomas is reviewed in detail. PMID- 8199194 TI - Immunotoxins against cancer. PMID- 8199195 TI - Integrin-mediated adhesion and signaling in tumorigenesis. PMID- 8199196 TI - The transforming activity of simian virus 40 large tumor antigen. PMID- 8199197 TI - Branch-point reactions in the biosynthesis of cholesterol, dolichol, ubiquinone and prenylated proteins. PMID- 8199198 TI - Impact of monocyte colony-stimulating factor upon beta-very low density lipoprotein (beta-VLDL) cholesterol metabolism in tetradecanoyl phorbol acetate derived THP-1 cells. AB - The effect of monocyte colony stimulating factor (M-CSF) on the beta-very low density lipoprotein (beta-VLDL) metabolism in THP-1 cells (human leukemia cell line) was studied. THP-1 cells treated with M-CSF decreased Latex Bead phagocytosis, but the cells incubated with 12-tetradecanoyl-phorbol-13-acetate (TPA) enhanced phagocytosis 2.5-fold. Binding activity of 125I-M-CSF to THP-1 cells was higher than that in THP-1 cells elicited with TPA. THP-1 cells incubated with M-CSF before TPA treatment were designated MT macrophages, and those incubated with M-CSF after TPA treatment were called TM macrophages. When these cells were incubated with beta-VLDL, the cholesterol ester content in MT macrophages was less than in TM macrophages. The uptake of [3H]cholesterol oleate beta-VLDL in MT macrophages was the same as in TM macrophages. The released radioactivity from [3H]cholesterol oleate-beta-VLDL loaded MT macrophages was higher than that from TM macrophages. Acid cholesterol esterase activity and ACAT activity were the same in both types of macrophages. Neutral cholesterol esterase activity was higher in MT than in TM macrophages. These results suggested that beta-VLDL-induced cholesterol ester deposition in THP-1 cells-derived macrophages was suppressed by M-CSF, when M-CSF acted at the stage of monocytes (THP-1 cells), and that the reduction of cholesterol ester might be due to enhanced release of cholesterol from the cells with high neutral cholesterol esterase activity. PMID- 8199199 TI - Native-like structure and self-association behavior of apolipoprotein A-I in a water/n-propanol solution. AB - The effect of n-propanol on the secondary and tertiary structure of human apolipoprotein A-I (apoA-I), an interfacial protein, was investigated using near and far ultraviolet (UV)-circular dichroism (CD) and fluorescence spectroscopy, as well as limited proteolytic digestion with trypsin, and cross-linking with bis(sulfosuccinimidyl) suberate. The structure of apoA-I in n-propanol (30%, v/v) was compared with that in Tris buffer and in reconstituted, spherical or discoidal, high density lipoproteins (rHDL). Addition of n-propanol to apoA-I in Tris buffer induces major changes in its near and far CD spectra: alpha-helical content increases by 27% and the near UV-CD spectrum becomes very similar to that of apoA-I in rHDL particles. Fluorescence spectral, lifetime, and polarization results, and quenching by KI confirm that major structural changes occur in the N terminal half of apoA-I as n-propanol is added: the Trp residues become more exposed to solvent than in buffer alone or in rHDL. Higher concentrations of guanidine hydrochloride or urea are required to denature apoA-I in n-propanol than in buffer alone, but a similar free energy of unfolding is observed. The N terminus of apoA-I is relatively resistant to trypsin digestion and the C terminus has equivalent digestion sites for apoA-I in the three states, but the kinetics of digestion are much slower in n-propanol and in rHDL compared to apoA I in Tris buffer. Cross-linking experiments reveal that dimers of apoA-I exist in n-propanol, in contrast to dimers plus multimeric aggregates in Tris buffer. From these results we conclude that in 30% n-propanol the structure of apoA-I approaches that of 'native' lipid-bound apoA-I, in contrast to its structure in the aqueous Tris buffer. PMID- 8199200 TI - Fatty acid uptake and metabolism in CaCo-2 cells: eicosapentaenoic acid (20:5(n 3)) and oleic acid (18:1(n-9)) presented in association with micelles or albumin. AB - In vivo, long-chain fatty acids are incorporated into bile salt micelles, which solubilize the hydrophobic fatty acids before they are transported across the unstirred water layer to the intestinal brush border membrane. In the present study we have used CaCo-2 cells, cultured on filter membranes as a model of human enterocytes, and compared presentation of fatty acids bound to albumin with a micellar form. Absorption of eicosapentaenoic acid and oleic acid from micellar solutions was 4-times faster than from fatty acid-albumin complexes after 5 h incubation, and resulted in a corresponding increase in triacylglycerol synthesis and secretion. Mass determination of newly synthesized, cell-associated triacylglycerol after 5 h incubation, indicated a 5-fold increase in cells exposed to a micellar solution versus albumin-complexed fatty acids. A 2-fold larger fraction of the absorbed fatty acids was incorporated into triacylglycerol than into phospholipids when the fatty acids were presented as micelles. Analysis by resistive pulse technique showed that secreted lipoproteins of density less than 1.006 g/ml were in the same size-range as chylomicrons derived from human plasma. In spite of an increased amount of secreted triacylglycerol from cells supplemented with micellar fatty acids, there was no increase in the mean size of these particles. Synthesis and secretion of triacylglycerol in cells exposed to eicosapentaenoic acid and oleic acid were similar regardless of whether the fatty acids were presented to the cells associated with albumin or micelles, although the total amount of triacylglycerol synthesized and secreted was highest with micelles. When incubating CaCo-2 monolayers with eicosapentaenoic acid or oleic acid bound to albumin, a similar amount of radioactivity was released as CO2 and acid soluble products into the medium with less than 3% of the lipids being oxidized after 5 h of incubation. The oxidation rate of fatty acids in cells incubated with micelles was increased 40 to 100%. In conclusion, micellar fatty acids are absorbed, metabolized and influence secretion of lipoprotein particles to a higher extent than albumin-bound fatty acids in CaCo-2 cells, and there is no major difference between eicosapentaenoic acid and oleic acid. PMID- 8199201 TI - Murine macrophages secrete factors that enhance uptake of non-lipoprotein [3H]cholesteryl ester by aortic smooth muscle cells. AB - We have recently demonstrated that macrophage conditioned medium (MP medium) and beta VLDL enhance cholesterol esterification in cultured aortic smooth muscle cells by LDL receptor mediated and other pathways (Stein, O. et al. (1993) Arteroscl. Thromb. 13, 1350-1358). In view of the presence of extracellular non lipoprotein cholesteryl ester (in the form of lipid droplets) in the atheroma, the effect of MP medium on the cellular uptake of liposomal cholesteryl linoleyl ether (CLE) or cholesteryl ester (CE) was studied. After 4 h incubation in MP medium, the uptake of liposomal [3H]CLE was up to 10-fold higher than in the presence of control medium of the same composition but not conditioned with macrophages (DV medium). Similar results were seen also with HSF derived from LDL receptor negative donors. The MP medium-stimulated uptake of liposomal [3H]CE resulted also in hydrolysis of 70-90% of the labeled compound, indicating that the [3H]CE was intracellular. While the MP medium effect on liposomal [3H]CLE uptake was evident after 4 h, its effect on [3H]cholesterol esterification by SMC in the presence of beta VLDL could be demonstrated only after 24 h. Addition of apoE to MP medium resulted in a small (30-40%) increase in the uptake of liposomal [3H]CLE; however, it was augmented more than 4-fold when apoE was added to DV medium. The MP medium effect on the uptake of liposomal [3H]CLE was interfered with by heparin, anti-LPL antibody or heparinase, while these treatments did not affect [3H]cholesterol esterification in the presence of beta VLDL. These results suggest that the interaction between SMC and two potential sources of lipids in atheroma, i.e., lipoproteins and non-lipoprotein lipid droplets, could be governed by different components of the MP medium. In the case of the lipid droplets, as modeled here in the form of liposomes, macrophage derived lipoprotein lipase could play a major role in cholesteryl ester transfer into SMC. PMID- 8199202 TI - The mechanism for the increased supply of phosphatidylcholine for the proliferation of biological membranes by clofibric acid, a peroxisome proliferator. AB - The metabolic changes induced by p-chlorophenoxyisobutyric acid (clofibric acid), a peroxisome proliferator, in hepatic glycerolipids for the supply of membrane phospholipids were studied. The administration of clofibric acid to rats caused hepatomegaly and an increase in hepatic contents of phosphatidylcholine (PtdCho) (1.13-fold on the basis of g liver and 1.50-fold on the basis of whole liver). The administration of the drug enhanced the formation in vivo of PtdCho from [3H]glycerol, which seemed to be due to the increase in activity of CTP:phosphocholine cytidylyltransferase. On the other hand, clofibric acid depressed the activity of phosphatidylethanolamine N-methyltransferase. The in vivo study using [3H]glycerol revealed that clofibric acid slightly reduced the secretion of PtdCho into circulation. On the other hand, the drug did not affect the turnover of PtdCho. These results may elucidate the metabolic alterations by which clofibric acid increases hepatic mass of PtdCho. The facilitated biosynthesis of PtdCho by the drug seemed to lead to the increased formation of phosphatidylserine and subsequently phosphatidylethanolamine. Physiological significance of the alterations in glycerolipid metabolism by clofibric acid was discussed in relation to biological action of the drug. PMID- 8199203 TI - Growth-dependent regulation of cellular ceramides in human T-cells. AB - The role of ceramide, a putative lipid second messenger in the regulation of cell growth, was investigated in T-lymphocytes. An inverse relationship between the cellular concentrations of ceramide and the proliferative capacity of human T lymphocytes was observed for cells treated with either interleukin-2 or phorbol ester plus ionomycin. The same relationship between cellular ceramide concentrations and DNA synthesis also was observed for cells derived from a cultured T-cell line, the Jurkat T-cells. Alternative approaches for modulating the cellular ceramide concentrations were employed to determine the relationship between sphingolipids and cell growth. Treatment of normal T-lymphocyte cultures with exogenous cell-permeable ceramide analogues or sphingosine stereoisomers decreased DNA synthesis. A similar effect was seen with stearylamine. Cells treated with D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of UDP-glucosyl:ceramide transferase, accumulated cellular ceramide concentrations and had decreased DNA synthesis. These results define a correlation between the concentration of cellular ceramides and the capacity of T lymphocytes to proliferate. However, the addition of bacterial sphingomyelinase to the T-cell medium caused an increase in ceramide concentrations (presumably at the plasma membrane), which did not affect cell growth. These results support the hypothesis that functionally distinct pools of ceramide may reside within the T cell. PMID- 8199204 TI - Synthesis of phosphatidylinositol 3,4-bisphosphate is regulated by protein tyrosine phosphorylation but the p85 alpha subunit of phosphatidylinositol 3 kinase may not be a target for tyrosine kinases in thrombin-stimulated human platelets. AB - To elucidate the mechanism involving synthesis of phosphatidylinositol 3,4 bisphosphate (PtdIns(3,4)P2), which is the main species of 3-phosphorylated phosphoinositides in activated blood platelets, we observed a correlation among protein-tyrosine phosphorylation, protein kinase C (PKC) activation, and PtdIns(3,4)P2 synthesis in these anucleate cells. Thrombin (1 U/ml) elicited marked protein-tyrosine phosphorylation, PKC activation, and PtdIns(3,4)P2 synthesis. In contrast, 1 microM 12-O-tetrade-canoylphorbol 13-acetate barely induced tyrosine phosphorylation and PtdIns(3,4)P2 synthesis although it strongly activated PKC. A variety of kinase inhibitors were tested for their ability to inhibit the thrombin effects. Both staurosporine and tyrphostin inhibited thrombin-stimulated tyrosine phosphorylation and PtdIns(3,4)P2 synthesis. H-7, which specifically, although weakly, inhibited PKC activation, had no effect on tyrosine phosphorylation and PtdIns(3,4)P2 production. Among the various kinase inhibitors tested, staurosporine was the most potent inhibitor of protein tyrosine phosphorylation and PtdIns(3,4)P2 synthesis, and there was a good correlation of the inhibition between these two parameters, although it also inhibited PKC activation. To examine the involvement of PtdIns 3-kinase, which is believed to play an important role in 3-phosphorylated phosphoinositide synthesis, we studied tyrosine phosphorylation and the association with tyrosine phosphorylated proteins of the p85 alpha subunit of PtdIns 3-kinase in thrombin stimulated platelets. We did not detect tyrosine-phosphorylated protein by Western blotting where p85 alpha was located. Similarly, when platelet lysates were precipitated with anti-p85 alpha antibodies and then blotted with anti phosphotyrosine antibodies, tyrosine-phosphorylated p85 alpha was undetectable. Furthermore, when the cell lysates were precipitated with anti-phosphotyrosine antibodies, no p85 alpha was found in the immunoprecipitates. These results show that PtdIns(3,4)P2 synthesis in stimulated platelets is mediated by tyrosine phosphorylation, as it is in proliferating cells, but the p85 alpha subunit of PtdIns 3-kinase may not be a target for tyrosine kinases and that staurosporine, though non-specific, would be a useful tool for elucidating signal transduction involving D-3-phosphorylated phosphoinositide generation and protein-tyrosine phosphorylation in blood platelets. PMID- 8199205 TI - Modifications of low density lipoprotein induced by the interaction with human plasma glycosaminoglycan-protein complexes. AB - Glycosaminoglycan (GAG)-protein complexes from human plasma were separated into low charge (LC-GP) and high charge (HC-GP) components. LC-GP and HC-GP differed with respect to GAG and protein composition and to molecular size. The in vitro interaction of both GAG-protein complexes with human LDL was investigated. LC-GP did not precipitate LDL. On the contrary, HC-GP formed insoluble complexes with LDL, following a biphasic behaviour on increasing HC-GP concentration. In the presence of a HC-GP/LDL ratio higher than 0.02 the interaction stoichiometry was shifted towards the formation of soluble complexes. Papain treatment of HC-GP completely prevented LDL precipitation. Moreover, the extent of HC-GP-induced precipitation of LDL was markedly reduced by the simultaneous addition of LC-GP. Data obtained with standard GAGs showed that heparin (HE) and chondroitin-6 sulphate (C6S) were the most effective ligands in precipitating LDL. However, the shape of precipitation curves was markedly different. C6S behaved similarly to HC GP, suggesting that GAG chains could play an important role in insoluble complex formation with LDL. Steady-state fluorescence anisotropy investigation indicated that HC-GP induced a significant decrease in the microviscosity of LDL hydrophobic region. This effect was no longer detectable after either addition of LC-GP or papain treatment of HC-GP. Differential scanning calorimetry (DSC) demonstrated that both lipid and protein components of LDL were affected by the interaction with HC-GP. The temperature of irreversible thermal unfolding of apo B100 was shifted to a lower value and a second peak appeared in the region of the reversible melting of cholesterol esters. Both the fluorescence anisotropy and the DSC data obtained with standard HE and C6S indicated that GAG chains were directly involved in affecting physico-chemical properties of complexed LDL. These results suggest that the interaction with plasma HC-GP could modify LDL structural properties. However, LC-GP is likely to act as a modulator, probably preventing the interaction between HC-GP and circulating LDL. PMID- 8199206 TI - Platelet-activating factor formation during oxidative modification of low-density lipoprotein when PAF-acetylhydrolase has been inactivated. AB - A PAF aggregating activity corresponding to 427 +/- 91, 668 +/- 111 and 1319 +/- 217 pg/mg protein was detected when LDL was preincubated at pH 3.5 or with 4 mM PMSF or both for 30 min (treatments that inactivate PAF-AH) and then oxidized with 20 microM Cu2+ at 37 degrees C for 24 h. This molecule was characterized as PAF by its chromatographic behavior on TLC and other established methods and was further characterized as 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16: PAF) by its retention time on reverse phase HPLC and by fast atom bombardment mass spectroscopy. Native LDL incubated under non oxidizing conditions, even when PAF-AH has been inactivated, or oxidized in the absence of PAF-AH inactivating agents or after pretreatment with 0.5 mM pBPB, does not produce detectable amounts of PAF. The kinetics of PAF formation in relation to PAF-AH activity, show that the apparent rate of PAF formation as well as its total amount depends on both the existence of oxidative conditions and the remaining PAF-AH activity the first hours following the onset of oxidation. Peroxidation of the phosphatidylcholine (PC) content of native LDL produces PAF-like aggregating activity much lower than that produced when intact LDL is oxidized and is not inhibited by BN 52021 as effectively as PAF produced by LDL peroxidation. Our results provide evidence that C16: PAF is formed during LDL peroxidation when PAF AH has been inactivated and it does not result as a product of peroxidation of the LDL-PC content. PMID- 8199207 TI - Shoulder arthroplasty new approach and design. PMID- 8199208 TI - Scapulocostal syndrome. AB - The scapulocostal syndrome, myofascitis of the shoulder muscles, is caused by altered posture, prolonged immobilization of the shoulder region or fixed scapular/spinal deformities. The author studied 440 patients ranging from 18 to 60 years of age whose altered posture caused deep pain in the shoulder region originating from the medial aspect of the scapular spine. Treatment consisted of infiltrating a trigger point in the subscapularis region of the medial aspect of the scapular spine (root of the scapular spine) with a mixture of 2cc plain 1% lidocaine hydrochloride (Xylocaine [Astra]) plus 1cc beta-methasone sodium phosphate and acetate suspension (Celestone Soluspan [Schering]) followed by physical therapy exercises. 190 patients (43.19%) received one block, 175 (39.77%) received two blocks, and 75 (17.04%) received three blocks. Upon completion of treatment, 97.7% of the patients were relieved of their discomfort and returned to their original occupation. PMID- 8199209 TI - Virginia's Birth-Related Neurological Injury Compensation Act. $54.5 million and 7 years later. PMID- 8199210 TI - POWs another war-same hardships. PMID- 8199211 TI - You be the expert! PMID- 8199212 TI - MSV health insurance. How the physicians' plan evolved. PMID- 8199213 TI - Health needs in the former Soviet states. PMID- 8199214 TI - Russian-American collaboration. Neurodevelopmental pediatric research. PMID- 8199215 TI - The Virginia Orthopaedic Society. The first 50 years. PMID- 8199216 TI - The physical therapy prescription. PMID- 8199217 TI - Single-stranded regions in yeast mitochondrial DNA revealed by pulsed-field gel electrophoresis. AB - The Klenow fragment of E. coli DNA polymerase together with pulsed-field gel electrophoresis (PFGE) have been used to investigate the presence of single stranded DNA (ssDNA) regions in yeast (Torulopsis glabrata) DNA. Electrophoretic profiles of total DNA from Rho+ (wild type) and Rho0 (no mitochondrial DNA) strains demonstrate that this method mediates the incorporation of labelled dATP into mitochondrial DNA (mtDNA), but not into chromosomal DNA. The majority of ssDNA (> 62%) has been found associated with the electrophoretically inert component, localized on the top of PFGE gels. Treatment with single-stranded nucleases allows the resolution of this immobile fraction into fast migrating, linear molecules of a heterogeneous size. The possibility that single-stranded tracts and their recombinogenic properties are responsible for the trapping of DNA in pulsed-field gels is discussed. PMID- 8199218 TI - Complement C3 fragments in urine: detection in systemic lupus erythematosus patients by western blotting. AB - We characterized urinary excretion of C3 fragments among patients with systemic lupus erythematosus (SLE) as a possible indicator of renal involvement. 28 patients, representing a broad range of disease activity were admitted to our study. Urinary proteins were separated on 4-20% gradient SDS-PAGE gels, under reducing conditions, and transblotted to nitrocellulose. Western blots were developed with a polyvalent goat-anti-human C3d antiserum, and an alkaline phosphatase-conjugated rabbit anti-goat IgG. Three patterns were obtained: 1) no bands detected; 2) bands suggesting the presence of intact C3; and 3) samples with additional low molecular (< 4 x 10(4)) bands. The 12 patients with no C3 bands had minimal disease activity (e.g. fatigue, arthralgia, arthritis, rash, oral ulcers). The seven patients with intact C3 patterns also had minimally active disease. Their primary clinical findings included fatigue, pleurisy, renal disease which had been treated, hemolytic anemia, and arthritis. Patients with low molecular weight C3 fragments in their urine formed two sub-sets, based upon their presenting features. The first group had severe disease and contained all patients with active lupus nephritis (n = 4), while the second consisted of non renal patients with primary clinical findings of moderate disease activity (e.g. thrombocytopenia, pneumonitis, arthritis). Our results suggest urinary excretion of low molecular weight C3 fragments correlates with active renal disease, but is a variable finding among SLE patients with non-renal manifestations of disease activity. PMID- 8199219 TI - Purification of recombinant adenomatous polyposis coli polypeptide chains from E. coli extracts by continuous-elution electrophoresis. AB - A polypeptide chain encoded by the exons 1-3 of the human adenomatous polyposis coli (APC) tumor suppressor gene was expressed as a maltose binding fusion protein (MBP) in E. coli to be used for immunization purposes. It turned out, that the APC-MBP fusion product of 60 kDa was deposited in bacterial inclusion bodies and, in addition, it was not retarded by an amylose affinity column, most probably due to an altered conformation of the chimeric molecule. For this reason, we established an alternative purification scheme, which took advantage of SDS-extraction followed by a high-resolution two-step continuous-elution electrophoresis (CEE) procedure. This purification method allowed us to obtain high yields of pure human APC exon 1-3-encoded proteins. The final yield of the pure APC polypeptide chains was estimated to represent 5-8% of the amount of SDS extracted E. coli lysate subjected to the first cycle of CEE. The purified APC molecules were successfully used for the development of specific antibodies. The CEE procedure described here represents a general purification method which is valuable in cases where fusion proteins are deposited as inclusion bodies in bacteria, or if affinity chromatography is precluded due to a conformation induced lack of ligand binding of the chimeric molecule. PMID- 8199220 TI - Electrophoresis of small DNA molecules in agaroses with different electroendosmotic properties. AB - The migration rate of DNA standards in agaroses with different electroendosmotic (EEO) properties was compared in order to find an alternative to polyacrylamide slab gels for the separation of small restriction fragments by electrophoresis. Slower migration of DNA molecules only a few hundred of base pairs in length was observed after raising the concentration of unmodified low EEO agarose in gels up to 6%. Resolution of low-molecular-weight DNA fragments was best achieved, however, with hydroxyethylated agaroses showing high or low EEO properties. An immediate application of the above results was to confirm the presence of the human cytomegalovirus BamH I-P subgenomic fragment (7.2 kb) in a recombinant pAT153 plasmid by restriction endonuclease analysis. PMID- 8199221 TI - Restriction sites as identification tags for the gene catalog: a 2D gel model. AB - In our effort to collect, organize and assemble data from lymphocyte cDNA libraries, we assign DNA restriction sites collectively to the spots on two dimensional (2D) gel patterns. In order to test the efficiency and reliability of such an approach, we have modeled the restriction analysis of cDNA libraries with a panel of restriction endonucleases. The work has two parts. In the first, we have chosen 255 proteins from the EMBL data base and determined whether or not their coding sequences contain restriction sites for the enzymes of our choice. In order to apply a sufficient discriminatory power we decided to use a relatively large number of cleaving enzymes with low and high cutting frequencies. In total, 13 restriction enzymes were chosen, which could distinguish 2(13) or 8192 different restriction site combinations. We have compiled a table in which the absence or presence of restriction sites yields a pattern of 'zeros' and 'ones'. Such a restriction pattern can be read as a binary number. The binary numbers with maximally 13 digits would uniquely assign each of the 255 proteins if the nucleotide sequences would be truly at random. As the restriction sites are not randomly distributed, the 'typing' does not yield a unique assignment. The choice of sequences was not random either. In fact, there are some human nucleotide sequences which possess the same cut number (the decimal equivalent of the binary number representing the restriction pattern). In spite of this redundancy, 141 coding sequences could uniquely be distinguished by the above treatment. In the second part of the project we have used the above mentioned coding sequences to prepare two-dimensional maps (plots of charge vs size) of the same kind as one obtains from experimental 2D gels and submitted such a map together with 13 maps of restriction enzyme treated populations to a computer image analysis. Ideally, one would expect results (cut numbers) congruent to those obtained in the first part of the work. In the modeled system we were confronted with 2D maps which closely resembled the experimental situation (e.g. some spots were close together and overlapping) and instances of incorrect spot detection yielding 'false cut numbers'. From 255 proteins we were able to assign unequivocally 161 proteins. To implement the model in an actual experiment we will perform the digestion with the restriction enzymes in duplicate, and only spots assigned the same cut number upon the two independent treatments will be considered as carrying a valid restriction tag. PMID- 8199222 TI - Capillary electrophoresis to measure sulfoesterase activity on chondroitin sulfate and heparin derived disaccharides. AB - Capillary electrophoresis was used to assay sulfoesterase activity on sulfated disaccharides derived from chondroitin sulfate, dermatan sulfate and heparin. The three sulfoesterases studied were chondro-4-O-sulfatase (EC 3.1.6.9) and chondro 6-O-sulfatase (EC 3.1.6.10) from Proteus vulgaris and heparo-2-O-sulfatase from Flavobacterium heparinum. Capillary electrophoresis was used to analyse sulfated disaccharide before and after sulfoesterase treatment and a change in migration time was indicative of the presence of sulfoesterase activity. This assay was used both on purified sulfoesterases and on minor sulfoesterase contaminants present in other enzyme preparations. The high sensitivity of capillary electrophoresis permits the elimination of 35S-radiolabeled substrates normally required to assay sulfoesterases. The high resolution of capillary electrophoresis allows the use of this assay on impure enzyme preparations containing high protein concentrations. PMID- 8199223 TI - The trajectories of spheres during agarose gel electrophoresis. AB - To develop a physical description of the gel-induced retardation of spheres during gel electrophoresis, the microscopic motion of single electrically charged latex spheres is statistically quantified here, by digital image analysis. To obtain adequate resolution in space, comparatively large spheres, 240 nm in radius, are used. The following observations are made during electrophoresis in a 0.2% agarose gel at 22 degrees C: (a) When a comparatively high field (3.0 V cm 1) is used, inelastic collisions result in field-induced trapping of spheres; no elastic collisions are observed. (b) Reduction of the field from 3.0 to 0.0 V cm 1 results in reverse migration of previously trapped spheres. (c) In the absence of trapping, the electrical field does not cause an alteration in the tortuosity of motion (i.e. motion in a field-perpendicular direction). (d) When results are obtained for a constant time between images (0.2 s), gel-dependent deviations from a true random walk are not observed in the absence of trapping. (e) When results are obtained as a function of time between images, significant gel dependent deviation from a random walk is observed. In the absence of trapping, the data presented here indicate that retardation is derived primarily from dissipative processes that are concentrated near gel fibers. However, steric effects have not yet been distinguished from hydrodynamic effects. PMID- 8199224 TI - Modulation of the activity of calpain II by phosphorylation--changes in the proteolysis of cyclic AMP-dependent protein kinase (peak II, DEAE). AB - The proteolysis of the 32P-labeled holoenzyme of cyclic AMP-dependent protein kinase (A-PKII:DEAE, peak II fraction) was analysed by SDS-polyacrylamide gel electrophoresis and autoradiography. The contaminants of the A-PKII and calpain II apparently did not interfere with the accuracy of this highly sensitive analysis. Phosphorylation of calpain II by the catalytic subunit of cyclic AMP dependent protein kinase (A-PK) greatly enhanced the proteolysis of A-PKII, whereas phosphorylation by protein kinase C (PK-C) or cyclic GMP-dependent protein kinase (G-PK) slightly altered the proteolysis. PMID- 8199225 TI - Wave packets analysis of two-dimensional protein maps: a new approach to study the diversity of immunoglobulins. AB - This report describes a mathematical approach for classifying two-dimensional (2D)-protein maps without spot detection or pattern matching. Analysis of electrophoretograms was performed using wave packet decompositions of the signals. The scanned images were automatically decomposed into a set of sub images organized in a tree structure. Each sub-image contained relevant information such as its energy, or entropy. Moreover the node position itself of the sub-image reflected a frequency localization. A distance was then defined using the tree repartition of these quantities. Finally a statistical clustering on the tree structures was performed, terminating with a classification of the images according to their repartition frequencies. The algorithm has been applied to classify immunoglobulin (Ig) light chain patterns and proved useful to automatically detect monoclonal, oligoclonal or polyclonal Igs. PMID- 8199226 TI - Identification and use of constitutive proteins for the normalization of high resolution electrophoretograms. AB - Quantitative inter-gel comparisons of proteins separated by high resolution two dimensional protein electrophoresis present a number of problems. These problems may arise from: variations in pipetting and other mechanical manipulations of samples, protein loss during transfer from the first to the second gel dimension, variations in staining, and/or variations in film development during autoradiography, in the case of radioactively labeled proteins. This study presents a discussion of these issues and a normalization algorithm to deal with variations, which relies on a class of proteins present in most biological samples which by their nature may be considered internal standards. This class consists of proteins which are controlled by constitutive genes. Constitutive genes are genes that are expressed constantly. We have developed an algorithm which is currently available as a subroutine, 'FINDCONS', in the computerized densitometry and protein comparison analysis program, developed by Olson & Miller (1988). This algorithm identifies potentially 'constitutive' proteins. A normalization method employing these potentially 'constitutive' proteins was compared to several others by examining 2D-electrophoretograms of proteins from developing gypsy moths (Lymantria dispar L.) insect tissue. Following normalization, inter-gel comparisons of spots, which were 'identified' as 'constitutive', were observed to vary less in density than when no normalization method was used, or when normalization based on total integrated spot density was used. In addition to its use as a normalization tool, this algorithm and the subroutine FINDCONS may be useful as an aid in biological studies to identify 'constitutive' proteins. PMID- 8199227 TI - Comparison of the Bio Image Visage 2000 and the GELLAB-II two-dimensional electrophoresis image analysis systems. AB - To compare the Visage 2000 analysis system (Bio Image, Ann Arbor, MI, USA) with the GELLAB-II analysis system (National Cancer Institute, Frederick, MD, USA), we used each to perform image analysis of the same 29 silver-stained two-dimensional electrophoresis (2DE) gel image files from a study of urinary proteins in metal recovery plant workers who had confirmed body burdens of cadmium. Visage, aided by interactive analysis, detected an average of 890 +/- 177.6 spots per gel, or a total of 25,800 spots, whereas GELLAB-II detected 1971 +/- 198.5 spots per gel, or a total of 57,160 (a 222% increase over the Visage system), without operator intervention. Visage automatically quantified 52.5% (13,556) of the spots; 47.2% (12,173), consisting mostly of larger spots, had to be quantified interactively with an image editor, and 0.3% (71) were not quantified. GELLAB-II automatically quantified all detected spots. After we interactively assigned the maximum allowed number of landmarks (30 for Visage and 52 for GELLAB-II), we found that Visage matched 657 +/- 211.2 spots per gel, and GELLAB-II matched all detected spots and also extrapolated an average of 1269 virtual spots per gel. Plots of densities from the two systems on selected spots showed excellent agreement, and both systems showed high correlation between their measurements of the beta-2 microglobulin spot densities and an independent radioimmunoassay quantification of the original urine samples. By comparing the regression of the densities of all spots with urinary cadmium (UCD) levels, we found that several of the same detected spots from each system were highly correlated. The densities of four acidic proteins with relative molecular weights of approximately 112,000 Da (as quantified by GELLAB-II but not by Visage) were highly correlated with UCD concentrations. These proteins are new candidate biomarkers of cadmium toxicity. We compared the estimated labor costs of using each system to analyse a hypothetical 20-sample (60 gels) 2DE study and found that GELLAB-II was six times less expensive to use than Visage, primarily because of the operator time required to do interactive error correction with the Visage system. PMID- 8199228 TI - Mechanical precision in two-dimensional electrophoresis can improve protein spot positional reproducibility. AB - Current methods for high resolution two-dimensional electrophoresis (2DE) of proteins are capable of separating over 5000 protein spots in one procedure. Running and analysing such 2DE gels requires skilled technical work. However, the variable reproducibility of spot positions means that, even under the best circumstances, one gel cannot be overlain directly on another for precise comparison. Therefore, new and improved technologies that enhance gel-to-gel reproducibility are required. To this end, we have designed and built a research instrument to test whether a precise mechanical device could improve the gel-to gel reproducibility by reducing the amount of distortion and positional variation between the first and second dimension gels. Other causes of poor reproducibility, including sample type and preparation, gel matrices and running conditions were not varied in order to limit this study to the mechanical variations inherent in current 2DE systems. We found that the sample standard deviation of pooled data for measured protein spot-to-spot distances in the prototype device was 1.3 mm as compared to 4.3 mm in a conventional 2DE system. These improvements support the possibility that greater automation of the multistep 2DE process will enhance reproducibility. This approach seems justified in order to achieve significantly better matching between gels and between results from different laboratories. PMID- 8199229 TI - Derivatization of yeast cytochrome c peroxidase with pentaammineruthenium(III). AB - Cytochrome c peroxidase (CCP) was derivatized using aquopentaammineruthenium(II) [a5RuIIH2O] resulting in stable, covalently-linked derivatives that were purified by cation-exchange FPLC. Spectrophotometric determination of a5RuHis:heme ratios allowed identification of two derivatives containing one a5RuHis per CCP molecule. The histidine-specific reagent, diethyl pyrocarbonate (DEPC), which reacted with three histidine residues in native CCP (6, 60, 96) at pH 7, reacted with only two histidines in both a5RuHisCCP species. X-ray crystallography showed that a5Ru is coordinated to His60 in one derivative [Fox et al. (1990) J. Am. Chem. Soc. 112, 7426]; HPLC and mass spectral analysis of the tryptic peptides of the other derivative identified a peptide (MW = 1469 Da) corresponding to residues 1-12 of CCP plus a5Ru, indicating His6 as the site of modification. Mass spectral analysis of native CCP, a5RuHis60CCP, and the a5RuHis6 derivative yielded MWs of 33,536, 33,717, and 33,901 Da, respectively, revealing that a second site is ruthenated in the His6 derivative. Mass spectral analysis of a shoulder separated from the a5RuHis60CCP FPLC peak also indicated the presence of CCP with bound a5Ru (MW = 33,718 Da). Differential pulse voltammetry of this shoulder, which has negligible a5RuHis absorption, gave a peak at -68 mV (vs NHE) which is in the range expected for reduction of a5RuIII (carboxylato) complexes, as well as a peak at 42 mV due to the presence of approximately 20% a5RuHis60CCP. The extent of ruthenation at sites other than histidine was unexpected and illustrates that a5RuIIH2O is less specific for histidine than previously thought. Activity measurements and stability of enzyme intermediates were measured to further characterize the a5RuCCP species and showed that the derivatives have similar properties to native CCP. PMID- 8199230 TI - Molecular modeling of phytochrome using constitutive C-phycocyanin from Fremyella diplosiphon as a putative structural template. AB - Phytochrome, the ubiquitous photosensor in green plants, is similar to C phycocyanin in a number of ways. We have produced a model of the phytochrome chromophore binding pocket based on the X-ray crystal structure of C-phycocyanin from Fremyella diplosiphon [Duerring et al. (1991) J. Mol. Biol. 217, 577-592]. Twenty residues around the chromophore binding site of C-phycocyanin were changed to the corresponding residues of Avena phytochrome A for the modeling. In the minimized model, Arg-318, Ala-319, the methylene of Ser-322, Leu-325, Gln-326, and Tyr-327 (using the numbering of the Avena sequence; Cys-323 is chromophore bound) form a pocket on one side of the chromophore. The other side of the chromophore lacks hydrogen-bond donors and is involved only in van der Waals contact with the chromophore. The overall structure of the model may be described as one peptide segment "anchoring" the chromophore hydrophobically, covalently, and electrostatically from several directions, while the other key peptide segment simply provides a hydrophobic surface for the chromophore to rest against. The red light absorbing (Pr) chromophore of the model is buried more deeply in the binding pocket than the far red light absorbing (Pfr) chromophore. This apparently reflects reduced compatibility of the chromophore with the pocket upon photoisomerization, which requires the insertion of hydrophilic parts of ring D into the hydrophobic core of the protein. This concept is consistent with the experimental evidence that photoisomerization of the Pr chromophore is followed by movement of the chromophore from its binding pocket. In the proposed model, increased exposure of hydrophobic portions of the Pfr chromophore compared to the Pr chromophore is consistent with the red shift observed in the first intermediate of the Pr to Pfr photoconversion. The proposed model may be tested by mutation experiments, thus providing a viable model to foster the current rapid progress of molecular biology in this field. PMID- 8199231 TI - Peptide nucleic acid (PNA). A DNA mimic with a peptide backbone. PMID- 8199232 TI - Thiolate and phosphorothioate functionalized fluoresceins and their use as fluorescent labels. AB - We report the syntheses of two new fluorescein derivatives, 3',6'-dihydroxy-3-oxo 2-[(phosphonothio)-acetyl]spiro[isobenzof uran- 1(3H),9'-9H-xanthene]-6 carboxylic acid hydrazide, disodium salt, a phosphorothioate fluorescein, and 3',6'-dihydroxy-3-oxo-2-(mercaptoacetyl)spiro[isobenzofuran-1(3H), 9'-9H- xanthene]-6-carboxylic acid hydrazide, a mercaptoacetyl fluorescein. The latter is derived from the first compound by hydrolysis of the phosphate. Direct nonenzymatic labeling of the maleimide-derivatized IgG molecule by the novel mercaptoacetyl fluorescein is discussed. We also present a new method of bioconjugating phosphorothioate-functionalized fluorophores to a maleimide derivatized protein, based on the alkaline phosphatase-catalyzed hydrolysis of the S-P bond of the phosphorothioate and the concomitant liberation of the fluorophore thiolate. This last species reacts in situ with the maleimide on the protein. A high degree of conjugation control is achieved in that modulation of the stoichiometry of the label and enzyme results in incorporation from seven to eight fluorophores per protein, depending on the ratio of the phosphorothioate fluorescein to alkaline phosphatase. The quantum yield of the mercaptoacetyl fluorescein relative to 6-carboxyfluorescein is 0.22 and lambda exc = 494 nm and lambda em = 517 nm. PMID- 8199233 TI - An immunotoxin with increased activity and homogeneity produced by reducing the number of lysine residues in recombinant Pseudomonas exotoxin. AB - Pseudomonas exotoxin A (PE) is a protein composed of 613 amino acids arranged into three major, and one minor, domains. Immunotoxins (ITs) containing PE38, a mutant form of PE which lacks the cell binding domain (Ia, amino acids 1-252) and 16 amino acids from domain Ib (amino acids 365-380), are extremely potent cytotoxic agents which can cause a complete regression of various human carcinomas grown in nude mice. However, these ITs are a mixture of several different chemical forms since the coupling between the antibody and the toxin may occur between either the light or heavy chain of the antibody and one of the four primary amino groups present on the truncated toxin. To modify the toxin with heterobifunctional crosslinking reagents only at specific sites, we replaced lysines 590 and 606 with glutamines and lysine 613 with arginine (PE38QQR). We also added two different peptide sequences, each containing a lysine residue, at the N-terminus of PE38. In one of these the sequence is ANLAEEAFK ("Lys" peptide), and in the other, the sequence is LQGTKLMAEE ("NLys" peptide). The mutant toxins were coupled using a thioether linkage to monoclonal antibody B3 which recognizes an antigen present in large amounts on many human cancers. PE38QQR-containing recombinant toxins can only be linked to an antibody through the N-terminal methionine or the lysine within the peptide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199234 TI - (Aminomethyl)phosphonate derivatives of oligonucleotides. AB - Oligothymidylate (aminomethyl)phosphonates have been prepared, and their enzymatic and physicochemical properties have been studied. The individual isomers of the protected dimers have been separated, characterized, and incorporated into oligonucleotides in which the backbone consists of alternating (aminomethyl)phosphonate and phosphodiester linkages. One of these net neutral, single isomer oligonucleotides forms a duplex with its complementary sequence which is more stable than the corresponding natural counterpart, whereas the other isomer is considerably less stable. Specificity of hybridization is maintained, as determined by the reduction in melting temperature observed upon the introduction of mismatches into the complementary strand of the duplex. The (aminomethyl)-phosphonate linkage is stable toward enzymatic degradation but can be hydrolyzed in aqueous solution at elevated temperature. PMID- 8199235 TI - Boronated starburst dendrimer-monoclonal antibody immunoconjugates: evaluation as a potential delivery system for neutron capture therapy. AB - Boron neutron capture therapy (BNCT) is based on the nuclear capture reaction that occurs when boron-10, a stable isotope, is irradiated with low-energy or thermal neutrons (< or = 0.025 eV) to yield high LET alpha particles and recoiling 7Li nuclei [10B + nth-->[11B]-->4He(alpha) + 7Li + 2.39 MeV]. Approximately 10(9) boron-10 atoms must be delivered to each target cell in order to sustain a lethal 10B(n,alpha)7Li reaction. If MoAbs are to be used for targeting boron-10, then it is essential that they recognize a surface membrane epitope that is highly expressed on tumor cells and that a large number of boron 10 atoms be attached to each antibody molecule. In order to heavily boronate MoAbs, we have utilized starburst dendrimers (SD), which are precise, spherical macromolecules composed of repetitive poly(amidoamino) groups. Second- and fourth generation dendrimers, having 12 and 48 reactive terminal amino groups and molecular weights of 2414 and 10,632 Da, respectively, were boronated using an isocyanato polyhedral borane, Na(CH3)3NB10H8NCO. The boronated starburst dendrimers (BSD), in turn, were derivatized with m-maleimidobenzoyl N hydroxysulfosuccinimide ester (sulfo-MBS). The MoAbIB16-6, which is directed against the murine B16 melanoma, was derivatized with N-succinimidyl 3-(2 pyridyldithio)propionate (SPDP). The MBS-derivatized BSD and SPDP-derivatized MoAb were reacted to yield stable immunoconjugates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199236 TI - Poly(pyrrolecarboxamides) linked to photoactivable chromophore isoalloxazine. Synthesis, selective binding, and DNA cleaving properties. AB - In an attempt to obtain DNA sequence-specific cleaving molecules, we have synthesized two types of hybrid groove binders composed of an isoalloxazine (flavin) chromophore linked through a polymethylenic chain to either a bis- or a tris(pyrrolecarboxamide) moiety related to netropsin and distamycin, respectively. In both types of molecules, the polymethylenic chain is linked to the alloxazine ring either in the N10 position or in the N3 position. As netropsin and distamycin, the hybrid derivatives preferentially bind to A + T rich sequences and recognize sequences such as 5'-ATTT. Upon visible light irradiation the flavin moiety undergoes a redox cycling process generating superoxide anion and hydroxyl radical. Generation of oxy radicals appears to be more efficient with the hybrids in which the polymethylenic chain is linked at the N10 position. The generation of oxy radicals results in the occurrence of single strand break in supercoiled DNA. Breaks preferentially occur in the vicinity of A + T-rich sequences. The advantage of flavin relative to other oxy radicals generating compounds such as ferrous-EDTA is that it does not require chemical reduction but can be reduced either by visible light or by cellular enzymes, both conditions being compatible with pharmacological constraints. PMID- 8199237 TI - Oligonucleotide-poly(L-lysine)-heparin complexes: potent sequence-specific inhibitors of HIV-1 infection. AB - Poly(L-lysine)-conjugated oligonucleotides complementary to the translation initiation region of the tat protein were tested for their capacity to inhibit HIV-1 replication in de novo infected cells. Sequence-specific antiviral effects were observed with these conjugates at 0.5 microM; their activity was transient, and the viral production was only delayed for a few days. Interestingly, their efficiency was significantly increased by the addition of heparin, a sulfated polyanion that also presents antiviral properties against HIV-1. A single addition, at the time of virus exposure, of the ternary complex formed between oligonucleotide-poly(L-lysine) (75 nM) and heparin (50 micrograms/mL) totally protects cells from HIV-1 infection. Primary interference with virus adsorption is essential for the strong antiviral effect. However, this protection remains strictly sequence specific as demonstrated in experiments performed with different HIV-1 isolates. As comparison, treatments that combine AZT and heparin at the same concentrations did not promote such a complete protection. PMID- 8199238 TI - Design and synthesis of a protein device that releases insulin in response to glucose concentration. AB - To synthesize a glucose-sensitive insulin-releasing protein device, insulin was esterified with methanol and connected to glucose oxidase with intervention of a disulfide compound, 5,5'-dithiobis(2-nitrobenzoic acid). On adding glucose to an aqueous solution containing the hybrid enzyme, the modified insulin was released. The amount of insulin released increased with increasing concentration of added glucose. The insulin release from the hybrid enzyme was specific to glucose. The activity of released insulin was about 80% of the unmodified insulin. PMID- 8199239 TI - Preparation and characterization of interleukin-2-gelonin conjugates made using different cross-linking reagents. AB - Conjugates of IL-2 with the ribosome-inactivating protein gelonin were prepared using heterobifunctional reagents to link the proteins via disulfide, acid labile, and noncleavable linkers. In each case, one protein was modified using 2 iminothiolane. The sulfhydryl groups so introduced were then reacted either with 2-nitro-5-dithiobenzoate groups or with iodoacetamido groups which had been introduced into the second protein. In the case of the acid-labile linkage, a reagent which forms a labile bond upon reaction with amino groups, 4 (iodoacetamido)-1-cyclohexene-1,2-dicarboxylic acid anhydride (its synthesis is described in this paper) was used to modify the toxin. The conjugates were separated from nonconjugated proteins by gel filtration on Sephadex G100 (SF). Each was analyzed with respect to its ribosome-inactivating activity, its ability to bind to the IL-2 receptor, and its in vitro cytotoxicity. The ribosome inactivating activity of gelonin was unaffected by modification with 2 iminothiolane and was retained in conjugates prepared using this reagent. Modification of the toxin with 4-(iodoacetamido)-1-cyclohexene-1,2-dicarboxylic acid anhydride to form the acid-labile link drastically reduced the activity of the toxin. However, the activity of the toxin was recovered following acid treatment to release the native protein. Conjugates containing each type of linkage exhibited both specific binding and selective cytotoxicity toward cells expressing the IL-2 receptor. The most potent of these toxins, that containing the disulfide linkage, exhibited a cytotoxicity which was 2 orders of magnitude greater than that of unconjugated gelonin. PMID- 8199240 TI - Acceptor stem and anticodon RNA hairpin helix interactions with glutamine tRNA synthetase. AB - The class I glutamine (Gln) tRNA synthetase interacts with the anticodon and acceptor stem of glutamine tRNA. RNA hairpin helices were designed to probe acceptor stem and anticodon stem-loop contacts. A seven-base pair RNA microhelix derived from the acceptor stem of tRNA(Gln) was aminoacylated by Gln tRNA synthetase. Variants of the glutamine acceptor stem microhelix implicated the discriminator base as a major identity element for glutaminylation of the RNA helix. A second RNA microhelix representing the anticodon stem-loop competitively inhibited tRNA(Gln) changing. However, the anticodon stem-loop microhelix did not enhance aminoacylation of the acceptor stem microhelix. Thus, transduction of the anticodon identity signal may require covalent continuity of the tRNA chain to trigger efficient aminoacylation. PMID- 8199241 TI - Methionine as translation start signal: a review of the enzymes of the pathway in Escherichia coli. AB - Methionine is the universal translation start but the first methionine is removed from most mature proteins. This review focuses on our present knowledge of the five enzymes sustaining the methionine pathway in translation initiation in Escherichia coli: methionyl-tRNA synthetase, methionyl-tRNA(fMet) formyltransferase, peptidyl-tRNA hydrolase, peptide deformylase and methionine aminopeptidase. The possible significance of retaining methionine as initiation signal is discussed. PMID- 8199242 TI - Sequence, structure and evolutionary relationships between class 2 aminoacyl-tRNA synthetases: an update. AB - The seven class 2 aminoacyl-tRNA synthetases that are alpha 2 dimers have previously been divided by sequence homology into class 2a (seryl-, threonyl-, prolyl- and histidyl-) and class 2b (aspartyl-, asparaginyl- and lysyl-). It has been more difficult to classify the glycyl-, phenylalanyl- and alanyl-tRNA synthetases which have different subunit stoichiometries and which did not apparently contain all three canonical class 2 motifs. New sequence and structural information relating to the three problematic synthetases will be discussed permitting a step forward to be taken in the understanding of the evolutionary relationships between the class 2 synthetases. PMID- 8199243 TI - Selectivity and specificity in the recognition of tRNA by E coli glutaminyl-tRNA synthetase. AB - The specific recognition by Escherichia coli glutaminyl-tRNA synthetase (GlnRS) of tRNA(Gln) is mediated by extensive protein:RNA contacts and changes in the conformation of tRNA(Gln) when complexed with GlnRS. In vivo accuracy of aminoacylation depends on two factors: competition between synthetases, and the context and recognition of identity elements in the tRNA. The structure of the tRNA(Gln):GlnRS complex supports studies from amber and opal suppressor tRNAs, complemented by in vitro aminoacylation of the mutated tRNA transcripts, that the glutamine identity elements are located in the anticodon and acceptor stem of tRNA(Gln). Recognition of individual functional groups in tRNA, for example the 2 amino group of guanosine, is also evident from the result with inosine substituted tRNAs. Communication between anticodon and acceptor stem recognition is indicated by mutants in GlnRS isolated by genetic selection with opal suppressor tRNAs which are altered in interactions with the inside of the L shaped tRNA. We have also used genetic selection to obtain mutants of GlnRS altered in acceptor stem recognition with relaxed specificity for amber suppressor tRNAs, and a more extensive mutational analysis shows the importance of the acceptor binding domain to accurate recognition of tRNA. PMID- 8199244 TI - Phenylalanyl-tRNA synthetase from Thermus thermophilus has four antiparallel folds of which only two are catalytically functional. AB - Phenylalanyl-tRNA synthetase from Thermus thermophilus has an alpha 2 beta 2 type quaternary structure and is one of the most complicated members of the synthetase family. Identification of PheRSTT as a member of class II aaRSs was based only on sequence alignment of the small alpha-subunit with other synthetases. The three dimensional crystal structure of the catalytic and 'catalytic-like' domains at 2.9 A resolution in PheRSTT is described. The alpha-subunit contains an antiparallel fold which includes signature motifs 1, 2 and 3, characteristic of class II synthetases. One of the three structural domains of the beta-subunit (alpha'-domain) is formed by a seven-stranded antiparallel beta-sheet surrounded by alpha-helices similar to catalytic domains in SerRS, AspRS and the alpha subunit of PheRSTT. The alpha beta heterodimer (alpha and alpha') exhibits essentially the same topology in the intersubunit region as in the known alpha 2 structures of class II aaRS's. The multimerization area of whole PheRSTT molecule comprises a quasi-tetrahedral four-helix bundle. PMID- 8199245 TI - Discrimination between transfer-RNAs by tyrosyl-tRNA synthetase. AB - We have constructed a model of the complex between tyrosyl-tRNA synthetase (TyrRS) from Bacillus stearothermophilus and tRNA(Tyr) by successive cycles of predictions, mutagenesis of TyrRS and molecular modeling. We confront this model with data obtained independently, compare it to the crystal structures of other complexes and review recent data on the discrimination between tRNAs by TyrRS. Comparison of the crystal structures of TyrRS and GlnRS, both of which are class I synthetases, and comparison of the identity elements of tRNA(Tyr) and tRNA(Gln) indicate that the two synthetases bind their cognate tRNAs differently. The mutagenesis data on tRNA(Tyr) confirm the model of the TyrRS:tRNA(Tyr) complex on the following points. TyrRS approaches tRNA(Tyr) on the side of the variable loop. The bases of the first three pairs of the acceptor stem are not recognized. The presence of the NH2 group in position C6 and the absence of a bulky group in position C2 are important for the recognition of the discriminator base A73 by TyrRS, which is fully realized only in the transition state for the acyl transfer. The anticodon is the major identity element of tRNA(Tyr). We have set up an in vivo approach to study the effects of synthetase mutations on the discrimination between tRNAs. Using this approach, we have shown that residue Glu152 of TyrRS acts as a purely negative discriminant towards non-cognate tRNAs, by electrostatic and steric repulsions. The overproductions of the wild type TyrRSs from E coli and B stearothermophilus are toxic to E coli, due to the mischarging or the non-productive binding of tRNAs. The construction of a family of hybrids between the TyrRSs from E coli and B stearothermophilus has shown that their sequences and structures have remained locally compatible through evolution, for folding and function, in particular for the specific recognition and charging of tRNA(Tyr). PMID- 8199246 TI - A 15N-1H nuclear magnetic resonance study on the interaction between isoleucine tRNA and isoleucyl-tRNA synthetase from Escherichia coli. AB - Imino 15N and 1H resonances of Escherichia coli tRNA(lIle) were observed in the absence and presence of E coli isoleucyl-tRNA synthetase. Upon complex formation of tRNA(lIle) with isoleucyl-tRNA synthetase, some imino 15N-1H resonances disappeared, and some others were significantly broadened and/or shifted in the 1H chemical shift, while the others were observed at the same 15N-1H chemical shifts. It was indicated that the binding of tRNA(lIle) with IleRS affect the following four regions: the anticodon stem, the junction of the acceptor and T stems, the middle of the D stem, and the region where the tertiary base pair connects the T, D, and extra loops. This result is consistent with those of chemical footprinting and site-directed mutagenesis studies. Taken together, these three independent results reveal the recognition mechanism of tRNA(lIle) by IleRS: IleRS recognizes all the identity determinants distributed throughout the tRNA(lIle) molecule, which induces changes in the secondary and tertiary structures of tRNA(lIle). PMID- 8199247 TI - Yeast aspartyl-tRNA synthetase: a structural view of the aminoacylation reaction. AB - The refinement of the crystal structure of a binary complex formed by yeast AspRS and tRNA(Asp) provided a detailed understanding of the recognition of tRNA by an aminoacyl-tRNA synthetase. The crystal structures of several complexes containing ATP, alone or with aspartic acid, were also determined and refined. These studies led to a complete description of the active site of the enzyme and to the elucidation of the location and interactions of the various substrates. Based on these structural results, a class II-specific pathway for the aminoacylation reaction can be proposed. PMID- 8199248 TI - Association of tRNA(Gln) acceptor identity with phosphate-sugar backbone interactions observed in the crystal structure of the Escherichia coli glutaminyl tRNA synthetase-tRNA(Gln) complex. AB - We isolated several mutants with nucleotide substitutions in alanine tRNA (tRNA(Ala)) that resulted in glutamine tRNA (tRNA(Gln)) acceptor identity in Escherichia coli. These substitutions were in three regions of tRNA structure not previously associated with tRNA(Gln) acceptor identity. Only the phosphate-sugar backbone moieties of these nucleotides interact with the enzyme in the previously determined X-ray crystal structure of the complex between tRNA(Gln) and glutaminyl-tRNA synthetase. We conclude that these sequence-dependent phosphate sugar backbone interactions contribute to tRNA(Gln) identity, and argue that the interactions help communicate enzyme recognition of the anticodon to the acceptor end of the tRNA and the catalytic center of the enzyme. PMID- 8199249 TI - The SKS of the KMSKS signature of class I aminoacyl-tRNA synthetases corresponds to the GKT/S sequence characteristic of the ATP-binding site of many proteins. PMID- 8199250 TI - Non-canonical substrates of aminoacyl-tRNA synthetases: the tRNA-like structure of brome mosaic virus genomic RNA. AB - A 3-D model of the tyrosylable tRNA-like domain of the genomic brome mosaic virus RNAs was built by computer modelling based on solution probing of the molecule with different chemical and enzymatic reagents. This model encompasses four major structural domains, including two peculiar substructures oriented perpendicularly and mimicking a tRNA structure, and a fifth domain which makes the connection with the rest of the viral RNA. After recalling the different steps that led to the present structural knowledge of the BMV tRNA-like domain, we review its novel structural features revealed by the modelling and that did not appear in older versions of 3-D models of this structure. These features comprise additional base pairs, hairpin loops, new tertiary long-range interactions, and a second pseudoknot. The main goal of this paper is to strengthen the validity of the model by establishing correlations between the putative 3-D conformation and the functional properties of the domain. For that, we show how the present structural model rationalises mutagenic and footprinting data that have established the importance of specific regions of the RNA for its recognition and aminoacylation by yeast tyrosyl-tRNA synthetase. We discuss further how the model corroborates mutational analyses performed to understand recognition of this RNA domain by the (ATP,CTP):tRNA nucleotidyl-transferase and by the viral replicase. The published mutants of the BMV tRNA-like domain fall into two classes. In one class, the mutants leave unchanged the overall architecture of the molecule, thereby affecting functions directly. In the second class, the overall architecture of the mutants is perturbed, and thus functions are affected indirectly. PMID- 8199251 TI - Ternary complex between elongation factor Tu.GTP and Phe-tRNA(Phe). AB - The effect of aminoacylation and ternary complex formation with elongation factor Tu.GTP on the tertiary structure of yeast tRNA(Phe) was examined by 1H-NMR spectroscopy. Esterification of phenylalanine to tRNA(Phe) does not lead to changes with respect to the secondary and tertiary base pair interactions of tRNA. Complex formation of Phe-tRNA(Phe) with elongation factor Tu.GTP results in a broadening of all imino proton resonances of the tRNA. The chemical shifts of several NH proton resonances are slightly changed as compared to free tRNA, indicating a minor conformational rearrangement of Phe-tRNA(Phe) upon binding to elongation factor Tu.GTP. All NH proton resonances corresponding to the secondary and tertiary base pairs of tRNA, except those arising from the first three base pairs in the aminoacyl stem, are detectable in the Phe-tRNA(Phe)-elongation factor Tu-GTP ternary complex. Thus, although the interactions between elongation factor Tu and tRNA accelerate the rate of NH proton exchange in the aminoacyl stem-region, the Phe-tRNA(Phe) preserves its typical L-shaped tertiary structure in the complex. At high (> 10(-4) M) ligand concentrations a complex between tRNA(Phe) and elongation factor Tu-GDP can be detected on the NMR time-scale. Formation of this complex is inhibited by the presence of any RNA not related to the tRNA structure. Using the known tertiary structures of yeast tRNA(Phe) and Thermus thermophilus elongation factor Tu in its active, GTP form, a model of the ternary complex was constructed. PMID- 8199252 TI - Translational regulation of the Escherichia coli threonyl-tRNA synthetase gene: structural and functional importance of the thrS operator domains. AB - Previous work showed that E coli threonyl-tRNA synthetase (ThrRS) binds to the leader region of its own mRNA and represses its translation by blocking ribosome binding. The operator consists of four distinct domains, one of them (domain 2) sharing structural analogies with the anticodon arm of the E coli tRNA(Thr). The regulation specificity can be switched by using tRNA identity rules, suggesting that the operator could be recognized by ThrRS as a tRNA-like structure. In the present paper, we investigated the relative contribution of the four domains to the regulation process by using deletions and point mutations. This was achieved by testing the effects of the mutations on RNA conformation (by probing experiments), on ThrRS recognition (by footprinting experiments and measure of the competition with tRNA(Thr) for aminoacylation), on ribosome binding and ribosome/ThrRS competition (by toeprinting experiments). It turns out that: i) the four domains are structurally and functionally independent; ii) domain 2 is essential for regulation and contains the major structural determinants for ThrRS binding; iii) domain 4 is involved in control and ThrRS recognition, but to a lesser degree than domain 2. However, the previously described analogies with the acceptor-like stem are not functionally significant. How it is recognized by ThrRS remains to be resolved; iv) domain 1, which contains the ribosome loading site, is not involved in ThrRS recognition. The binding of ThrRS probably masks the ribosome binding site by steric hindrance and not by direct contacts. This is only achieved when ThrRS interacts with both domains 2 and 4; and v) the unpaired domain 3, which connects domains 2 and 4, is not directly involved in ThrRS recognition. It should serve as an articulation to provide an appropriate spacing between domains 2 and 4. Furthermore, it is possibly involved in ribosome binding. PMID- 8199253 TI - Preimplantation development of in vitro-matured and in vitro-fertilized ovine zygotes: comparison between coculture on oviduct epithelial cell monolayers and culture under low oxygen atmosphere. AB - The roles of medium composition, serum source, embryo coculture, and culture under low O2 conditions on the development of in vitro-matured and in vitro fertilized (IVMF) ovine zygotes were investigated in three separate experiments. In the first experiment, the proportion of cocultured IVMF zygotes developing to the blastocyst stage was significantly higher (38.0% vs. 3.5%; p < 0.05) than that of non-cocultured zygotes treated within three embryo culture media (TCM-199 + 10% fetal bovine serum [FBS]; bicarbonate-buffered, glucose-free synthetic oviduct fluid medium [mod-SOFM] + 10% FBS; and bicarbonate-buffered BSA-free Tyrode's salt solution [mod-TALP] + 10% FBS) under a 5% CO2 atmosphere in air. In a second experiment, a significantly higher (p < 0.05) proportion of cocultured zygotes placed in TCM-199 medium survived to the blastocyst stage (37.4% blastocysts vs. 23.4% in mod-SOFM). No significant effect of serum (FBS vs. human serum [HS]) was observed on embryonic development, but coculture was confirmed to exert a significant influence on development to the blastocyst stage. In the final experiment, survival of the embryo under a reduced oxygen (5% CO2:5% O2:90% N2) atmosphere was investigated. In contrast to results in the initial experiments, embryonic survival was significantly higher (p < 0.05) in the non cocultured treatment groups (21.9% blastocysts vs. 0.4% for cocultured zygotes). Serum source also had a significant (p < 0.05) influence upon the development of non-cocultured zygotes: 32.3% of zygotes cultured with HS progressed to the blastocyst stage vs. 11.5% of zygotes cultured in FBS-supplemented medium. These results have characterized two distinct culture environments, each capable of supporting the development of high frequencies of unselected IVMF zygotes to the blastocyst stage in vitro. PMID- 8199254 TI - Localization of inhibin and activin binding sites in the testis during development by in situ ligand binding. AB - Inhibin and activin are related proteins thought to be potential paracrine regulators of testicular development and maintenance of spermatogenesis. Messenger RNA and proteins immunologically related to both factors have been identified in the adult testis. However, the role(s) of these factors in paracrine regulation of testicular function is poorly understood. To identify potential targets for inhibin and activin in immature and adult testis, we used in situ binding of [125I]-labeled ligands to localize and describe the distribution of binding sites for inhibin and activin in testes of 15-, 18-, 21-, 30-, 45-, and 60-day-old rats. Nonspecific binding was defined as that occurring in the presence of a 1000-fold excess of unlabeled recombinant human (rh) inhibin or activin. [125I]-Inhibin was found to bind to interstitial cells throughout development. Inhibin binding was shown to co-localize with cells that showed positive staining for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). Competition studies demonstrated that this binding was indeed specific for inhibin. In contrast, [125I]-activin showed two distinct patterns of binding. First, [125I]-activin was shown to bind in a non-stage-dependent manner to cells located in the basal compartment of the seminiferous tubules in testis obtained from animals of all ages studied. Binding of [125I]-activin in the periphery of the tubule could be inhibited entirely by coincubation with excess unlabeled activin and partially with excess unlabeled inhibin. The ability of inhibin to compete with activin for binding appeared to be more pronounced in younger animals. In 45- and 60-day-old animals, a second stage-dependent component of [125I]-activin binding was also apparent. This binding was localized to spermatids found in stage VII-VIII tubules and was inhibited by the presence of excess activin, but not inhibin. These results indicate that inhibin can bind specifically to testicular interstitial cells throughout development and may be an important regulator of Leydig cell testosterone production or interstitial cell function. In contrast, activin appears to bind in a specific and stage dependent manner to receptors or high-affinity binding proteins on spermatids as well as to sites on the periphery of all seminiferous tubules. These results support the hypothesis that both activin and inhibin may act at several levels to regulate proliferation or differentiation of germ and Sertoli cell function as well as to modulate interstitial cell activity. PMID- 8199255 TI - Variation in reproductive photoresponsiveness in a wild population of meadow voles. AB - Individual variation in reproductive photoresponsiveness has been documented in laboratory colonies of several species of rodents. When maintained on short day lengths, some individuals experience complete gonadal regression, others undergo little if any gonadal regression, and still others show intermediate levels of responsiveness. In the present research, a combination of laboratory and field studies explored the potential importance of this kind of variation for the control of seasonal breeding in a wild population of meadow voles (Microtus pennsylvanicus). A sample of adult males was trapped in central Pennsylvania during the summer when all were in breeding condition. When exposed to short day lengths in the laboratory, these males showed the entire range of variation in responsiveness noted above and, correlatively, variation in the loss in body weight induced by this treatment. A sample of males trapped in the wild just before the winter solstice showed the same distribution of variation as did the males housed on short day lengths in the laboratory, and thus, as might be expected, a few pregnant and lactating females were also trapped at this time. Longitudinal studies over a 42-wk period revealed that the variation reflects the degree to which the testes regress in response to short-day exposure rather than the rate at which they regress. Finally, studies with laboratory-born voles demonstrated that the variation is independent of age. In total, these studies demonstrate that the variation in reproductive photoresponsiveness previously seen only in laboratory colonies of rodents indeed has relevance for understanding the seasonal control of reproduction in the wild. PMID- 8199256 TI - Uterine vascular changes after unilateral intrauterine infusion of indomethacin and prostaglandin E2 to rats sensitized for the decidual cell reaction. AB - Uterine extracellular fluid volume (ECFV), vascular permeability (VP), and blood flow (BF) were assessed after unilateral infusion of PBS, 0.05 mM indomethacin (IM), or IM plus 1 mg/ml prostaglandin (PG) E2 (PGE2) into uteri of rats sensitized for decidualization. The study was intended to determine the importance of PGE2 in mediating uterine vascular changes during early decidualization. Uterine ECFV was assessed by the uterine volume of distribution of 51Cr-EDTA, and uterine VP by the rate of change of the uterine volume of distribution of 125I-albumin, after i.v. injection of the respective tracers. Uterine BF was determined by the radioactive microsphere technique. ECFV and VP were significantly higher in infused than in control horns after both 10 and 20 h of PBS infusion (p < 0.05). Infusion of IM abolished these vascular changes while coinfusion of PGE2 with IM returned ECFV and VP to levels not significantly different from those associated with PBS infusion. Infusion of PBS resulted in proportionate increases in both uterine weight and total uterine BF for infused horns (p < 0.05) whereas neither of these variables changed after infusion of IM. Infusion of IM+PGE2 resulted in significantly reduced tissue BF (in microliter/min/mg) to infused horns because increases in uterine weights were not matched by proportionate increases in total BF. We conclude that PGs are essential for the increases in uterine VP and ECFV that precede endometrial decidualization and that PGE2 is sufficient to accomplish these vascular changes. Whereas PGs appear necessary for the increases in total uterine BF that maintain constant tissue BF during early decidualization, PGE2 alone does not appear to serve this function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199257 TI - Acute effects of prostaglandin F2 alpha, luteinizing hormone, and estradiol on second messenger systems and on the secretion of oxytocin and progesterone from granulosa and early luteal cells of the ewe. AB - Previous reports have suggested that gonadotropins, estradiol, and prostaglandin F2 alpha (PGF2 alpha) have varying effects on progesterone and oxytocin synthesis or secretion in cultured granulosa and luteal cells collected at different stages of the estrous cycle. The experiments reported here were designed to investigate whether effects of these agonists on secretion of hormones and their coupling to second messenger systems changed around the time of ovulation. Granulosa cells and Day 2 luteal cells of the ewe were cultured for three days and then treated for 30 min with varying doses of PGF2 alpha, LH, or estradiol. LH increased intracellular cAMP at both stages, but granulosa cells were more responsive in terms of both minimum effective dose (10 compared with 100 ng/ml) and degree of stimulation. LH caused no change in intracellular inositol phosphate levels. Both granulosa and early luteal cells responded to LH treatment by an increase in progesterone output in a dose-responsive fashion. PGF2 alpha increased inositol phosphate accumulation in cells collected at both stages of the cycle. All doses tested (10(-6)-10(-8) M) stimulated the release of oxytocin into the culture medium from both granulosa and luteal cells. Progesterone secretion was also increased, but only at the highest dose (10(-6) M). Estradiol treatment (10(-6) M) did not affect either the inositol phosphate or cAMP second messenger systems, but it did inhibit the secretion of oxytocin from granulosa cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199258 TI - Chemotaxis and chemokinesis of human spermatozoa to follicular factors. AB - Human spermatozoa accumulate in vitro in diluted follicular fluids obtained from follicles from which the eggs have been fertilized. Using capillary assays under a variety of experimental conditions (ascending or descending gradients of follicular fluid, or no gradient at all) and microscopic assays in which individual spermatozoa could be followed, we found that the sperm accumulation in follicular fluid was the result of both sperm chemotaxis and chemokinesis and eventually hyperactivation-like motility. We determined the optimal conditions for sperm accumulation, which involved sperm preincubation (possibly to induce sperm capacitation) and proper dilution of follicular fluid. In all the assays, the net accumulation was low, probably reflecting the chemotactic responsiveness of only a small fraction of the sperm population at any given time. We partially fractionated follicular fluid in a Centricon microconcentrator (Amicon, Danvers, MA) and by acetone precipitation, and found that at least one of the chemotactic factors is a small (< 10-kDa) molecule that is probably nonhydrophobic. This is the first time that sperm chemotaxis and chemokinesis in response to a follicular factor(s) in mammals has been established and has been distinguished from other processes that might cause sperm accumulation. The physiological significance of these findings is discussed. PMID- 8199259 TI - Sequential acquisition of chemotactic responsiveness by human spermatozoa. AB - Recent studies have indicated that human spermatozoa respond to follicular fluid by attraction to chemotactic factor(s) in the fluid, accompanied by enhancement of motility and ultimately hyperactivation. In this study, we quantified the sperm response. We exposed spermatozoa to a gradient of a chemotactically active fraction of follicular fluid (denoted as "the attractant") and separated the spermatozoa that accumulated in the attractant and those that did not. We thus obtained two subpopulations: one enriched with chemotactically responsive spermatozoa, and one deficient in such spermatozoa. The fraction of the responsive spermatozoa out of the total sperm population was 2-12% at any measured time point. With time, the responsive spermatozoa lost their ability to be attracted, while such activity was gradually acquired by the subpopulation originally deficient in responsive spermatozoa. These results indicate that the identity of responsive spermatozoa is continuously changing. If the in vitro results are representative of the physiological conditions in vivo, they imply that the role of sperm chemotaxis combined with enhanced motility may be to select capacitated spermatozoa and bring them to the egg. Such a mechanism may, over an extended period of time, increase the prospect that an egg will meet capacitated spermatozoa as soon as it ovulates. PMID- 8199260 TI - Characterization, localization, and regulation of receptors for insulin-like growth factor I in the baboon uterus during the cycle and pregnancy. AB - The objective of this study was to determine the presence, regulation, and localization of specific receptors for insulin-like growth factor I (IGF-I) in primate reproductive tissues. Uteri were obtained from baboons either during the menstrual cycle, after ovariectomy with or without steroid treatments, or during early pregnancy (Days 18-60 postovulation [PO]). Placental and decidual tissues were collected from baboons during late pregnancy (Days 130-160). Localization of type I IGF receptor was determined by indirect immunocytochemistry (alpha IR3 antibody), and levels of type I IGF receptors were determined by affinity cross linking and binding assays. Specific staining for type I IGF receptors was present in the membranes of glandular epithelial cells throughout the cycle and early pregnancy; however, there was a decrease in staining intensity by the late luteal phase and also throughout early pregnancy compared to the late follicular phase. Specific receptor staining was absent in stromal cells throughout the cycle. By Day 19 PO, stromal cells directly under the trophoblast were positive for type I IGF receptor, and an increase in stromal staining at the implantation site was observed as pregnancy proceeded. Stromal staining was apparent in non implantation site tissue by Day 32 PO. Some placental villi showed positive receptor staining as early as on Day 18 PO, and an increase in the number of positive villi was apparent as pregnancy progressed. An 125I-IGF-I-protein complex of approximately 140,000 daltons, corresponding to the alpha subunit of the type I IGF receptor, was detected in endometrial, placental, and decidual membranes. The intensity of this signal was high in endometrium from the follicular phase, whereas low levels were detected in endometrium from the luteal phase. Throughout early pregnancy, alpha receptor subunit was present in placental and decidual membranes; alpha receptor subunit increased in placenta as pregnancy proceeded. An additional 125I-IGF-I-protein complex of 43,000 daltons, corresponding to IGF binding protein-1 (IGFBP-1), was present in decidual membranes and appeared to increase as pregnancy proceeded. Specific binding of 125I-IGF-I to placental membranes was displaced by unlabeled IGF-I and alpha IR3 antibody, whereas both unlabeled IGF-I and IGF-II competed equally for binding to decidual membranes. Scatchard analysis of 125I-IGF-I binding to placental membranes revealed a single class of high-affinity receptors (KD = 2.35 +/- 0.8 nM; mean +/- SEM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8199261 TI - Effects of toxic levels of lead on gene regulation in the male axis: increase in messenger ribonucleic acids and intracellular stores of gonadotrophs within the central nervous system. AB - Lead is a male reproductive toxicant. Lead exposure results in a general suppression of the hypothalamic-pituitary-testicular (HPT) axis in male rats. The mechanism(s) for this disruption by lead is unknown. Toxic lead levels seem to disrupt central nervous system (CNS) control of the HPT system, resulting in a decrease in serum testosterone levels and sperm concentrations. A study designed to elucidate the mechanisms accounting for the disruption of the normal function of the male axis by toxic lead levels at the molecular level demonstrated a 2-3 fold enhancement of mRNA levels of GnRH and the tropic hormone LH. A 3-fold increase of intracellular stores of LH was also found. Because mRNA levels of LH and GnRH and pituitary levels of stored LH are proportional to blood levels of lead, we hypothesize that lead interferes with the normal release of tropic hormones and disrupts hormonal feedback mechanisms. The observed pleiotropic effects of lead upon the male axis and other systems may be explained by simple and unique competition by lead with normal metal ion binding sites that govern genetic control of specific genes. PMID- 8199262 TI - Plasminogen activator production by the granulosa layer is stimulated by factor(s) produced by the theca layer and inhibited by the luteinizing hormone surge in the chicken. AB - The stages of follicular maturation of a preovulatory follicle in the hen can be divided into an extended proliferative phase (prior to LH surge) and a brief ovulatory phase (after LH surge). Previous studies suggest involvement of plasminogen activator (PA) in both the proliferative and ovulatory phases. The goals of the present study were 1) to determine whether PA production by granulosa and theca is dependent upon interaction of the two cell layers; 2) to investigate whether the structural difference of the stigma (site of follicular rupture) and nonstigma regions of the theca layer affect PA production; 3) to determine whether there is a change in the ability of the granulosa layer and stigma or nonstigma regions of the theca layer to produce PA as the follicle makes the transition from the proliferative to the ovulatory phase; and 4) to characterize the type(s) of PA produced by the hen follicle. Equal proportions of the granulosa layer (10-mm diameter) and stigma or nonstigma regions of the theca layer (10 mg) obtained from the F1 preovulatory follicle 8 h before ovulation (before LH surge) or 2 h before ovulation (after LH surge) were incubated alone or in combination for 24 h. PA was measured in tissue homogenates and medium by use of the chromogenic substrate S-2251. The granulosa layer or stigma or nonstigma regions of the theca layer incubated alone and obtained either 8 h or 2 h before ovulation had very low amounts of PA activity in the medium and tissue homogenates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199263 TI - Distinctive features of the gametes and reproductive tracts of the Asian musk shrew, Suncus murinus. AB - Insectivora are of special interest as the most primitive of the eutherian mammals, but essentially nothing is known of their gamete function. In this respect, the Asian musk shrew (Suncus murinus), investigated in the present study, displays many idiosyncrasies. In the epididymis, the giant acrosome undergoes further stabilization, its unusual resilience being especially evident in a "rim" created by a persistent close alignment of the outer acrosomal and overlying plasma membranes. However, until spermatozoa reached a gland on the vas deferens, no post-testicular change was demonstrable in the sperm head surface, the unusual nature of which was indicated by a dorso-ventral differentiation, by an inability to auto-agglutinate or to bind to the homologous zona pellucida, and by an insensitivity to anti-sperm immunoglobulin IgG in fresh serum. At mating, only about 1 x 10(6) spermatozoa are inseminated as far as the anterior vagina with plug formation. Within the small (6 mm) fallopian tube, the isthmus and ampulla are sharply delineated by their contractile activity and epithelial character; there is evidence of some sperm entry into isthmic crypts and a tendency for ipsilateral ovarian control of sperm transport to the tubal ampulla. The cumulus oophorus does not undergo preovulatory mucification and expansion, is characterized by persistent intercellular gap junctions, and is insensitive to hyaluronidase and trypsin. It is unclear how the compact cumulus is penetrated at fertilization. The giant acrosome contains acrosin and an unusually temperature dependent cumulytic activity; it is intact in motile ampullary spermatozoa but appears to be discharged before reaching the zona pellucida. Since eggs were not penetrated in the presence of ampullary spermatozoa until 4-10 h after ovulation, Suncus spermatozoa spend a long period in the female before they can fertilize. The determinants of sperm function, including capacitation and the acrosome reaction (AR), may depend on a different set of controls in Suncus, perhaps as a legacy of the resilient giant acrosome. This possibility could be examined in other Crociduran and Soricine shrews selected according to acrosome size. PMID- 8199264 TI - Tissue inhibitor of metalloproteinases (TIMP-1) produced by granulosa and oviduct cells enhances in vitro development of bovine embryo. AB - Embryogenesis-stimulating activity (ESA) was found in serum-free conditioned media (CM) of bovine cumulus/granulosa cells (BGC) and bovine oviductal epithelial cells (BOEC). The CM of BGC (BGC-CM) contained two molecular species of ESA, one with a low molecular weight (M(r) 30,000) and another with a high molecular weight (M(r) 80,000); but only the activity with low molecular weight was detected in CM of BOEC by gel-permeation chromatography. The smaller ESA (embryogenin-1) in BGC-CM was purified to homogeneity, as a common activity in both CM by a combination of gel-permeation chromatography, ion-exchange chromatography, and reverse-phase HPLC. Embryogenin-1 has a molecular weight of 31,100 (reduced) and has been identified as a bovine tissue inhibitor of metalloproteinase-1 by NH2-terminal amino acid sequence analysis. Western blot analysis, anti-proteinase activities against metalloproteinases, and the nucleotide sequence of cDNA isolated from a lambda gt11 cDNA library of the bovine ovary by a polyclonal antibody against embryogenin-1. These data suggest that the tissue inhibitor of metalloproteinase-1 produced by BGC and BOEC is a major ESA for in vitro development of bovine embryos. PMID- 8199265 TI - Regulated storage and subsequent transformation of spermatozoa in the fallopian tubes of an Australian marsupial, Sminthopsis crassicaudata. AB - The disposition of spermatozoa in the female tract of the dasyurid marsupial, Sminthopsis crassicaudata, was examined before and after ovulation, by transillumination using differential interference optics. At 6-30 h after mating in females with maturing follicles, spermatozoa were restricted to special storage crypts that define the isthmus of the Fallopian tube. These spermatozoa were mostly immotile and were spear shaped, except for 50-200 vanguard spermatozoa within anterior crypts that were T shaped due to a rotation of the head on the tail. After ovulation and arrival of eggs in the narrow upper ovarian segment of the tube, several hundred isthmic spermatozoa migrated to that region, dispersed singly or in small groups of variable motility with some festooned around eggs. Most clearly displayed a T configuration, and subsequently, those remaining in the isthmic crypts also adopted a T shape in situ. The motility of mature epididymal spermatozoa and of those flushed from the isthmus before and after ovulation was similar in vitro, and all were spear shaped except for some T shaped isthmic spermatozoa recovered after ovulation. However, neither spear- nor T-shaped active isthmic spermatozoa ever adhered to the zona pellucida when incubated with eggs. We conclude that transport to and storage of spermatozoa in the isthmus of the Fallopian tube, and their later migration up to the fertilization site and coincident transformation to a T shape, all are closely regulated by the ovarian follicular cycle in Sminthopsis. Only on reaching the upper ovarian segment of the Fallopian tube do Sminthopsis spermatozoa appear to be able to bind to the egg, when the T shape brings the whole surface area of the acrosome into apposition with the zona pellucida. These observations are discussed with special reference to sperm capacitation, sperm penetration mechanisms, and the different idiosyncratic designs of the sperm head in marsupial and eutherian mammals, respectively. PMID- 8199266 TI - Protein kinase C, an inhibitor of oxytocin-stimulated phasic myometrial contractions. AB - One of the roles previously reported for protein kinase C (PKC) is modulation of the activity of the phosphatidylinositol signaling pathway. Studies were performed to test the hypothesis that activation of PKC results in inhibition of agonist-stimulated phasic myometrial contractions: contractions that appear to be mediated by phosphatidylinositol signaling mechanisms comparable to those producing cytosolic calcium oscillations. In vitro isometric contraction studies were performed using myometrium from adult Sprague-Dawley rats. Oxytocin and aluminium fluoride (a G-protein activator) produced comparable increases in phasic contractile activity. Phorbol 12,13-dibutyrate (PDB) significantly suppressed agonist-stimulated phasic myometrial contractions; in contrast, phorbol 13,20-diacetate (PDA), an inactive phorbol ester, had no significant effect on myometrial contractions. Prolonged exposure of myometrial tissue to PDB failed to down-regulate myometrial PKC and had no consistent effect on spontaneous and oxytocin-stimulated phasic contractions. These studies have provided support for a role for PKC as an intracellular regulator of the phosphatidylinositol signaling pathway, which itself appears to be part of the myometrial calcium oscillator that results in agonist-stimulated phasic myometrial contractions. PMID- 8199267 TI - pH-sensitive dissociation and association of beta-N-acetylhexosaminidase from boar sperm acrosome. AB - beta-N-Acetylhexosaminidase (beta-Hex, EC, 3.2.1.52) was released from cauda epididymal boar sperm by treatment with ionophore A23187, indicating that this enzyme is localized in the acrosome. beta-Hex was extracted on a large scale, with 2% acetic acid containing 0.2% Brij 35, from washed ejaculated sperm. By gel filtration chromatography, beta-Hex was separated into a high-molecular-weight fraction (beta-Hex I) and a low-molecular-weight fraction (beta-Hex I). beta-Hex I, which is predominant under acidic conditions (pH 6.5), dissociated into beta Hex II under alkaline conditions (pH 7.4). beta-Hex II, converted from beta-Hex I, associated again to form beta-Hex I under acidic conditions. By sequential chromatography on ion-exchange, lectin, gel filtration, and ion-exchange HPLC columns, beta-Hex I and II were purified 1200-fold and 4000-fold, respectively, with a combined recovery of 23% as measured with synthetic substrate. An inhibitor of beta-Hex, O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N phenyl-carbamate (PUGNAC), reduced the in vitro fertilization rate in porcine cumulus-enclosed eggs, but barely changed the rate when cumulus-free eggs were used. beta-Hex I was shown to possess cumulus dispersion activity, suggesting that beta-Hex plays a role in the passing by sperm through cumulus cells before they bind to the zona pellucida. PMID- 8199268 TI - Systemic and intraluteal infusion of inhibin A or activin A in rhesus monkeys during the luteal phase of the menstrual cycle. AB - The endocrine or local actions of inhibin-related peptides synthesized by the primate corpus luteum (CL) remain undefined. This in vivo study was designed to determine whether exogenous inhibin or activin modulates pituitary gonadotropin secretion and the functional life span of the CL during the luteal phase of the menstrual cycle. Beginning at midluteal phase of the cycle, either vehicle or 1 microgram/h of recombinant human inhibin A or activin A (n = 3-6 per treatment group) was infused into rhesus monkeys via the jugular vein (i.e., peripheral infusion) or directly into the CL (i.e., intraluteal infusion) by means of an osmotic minipump for 7-14 days. Daily samples of saphenous venous serum were assayed for estradiol (E) and progesterone (P) content by RIA, and for FSH and LH levels by bioassay. Intraluteal infusion of inhibin or activin did not alter circulating P levels or the length of the luteal phase compared to those values in vehicle-infused controls. Likewise, LH levels were not different between the three groups. However, FSH levels declined progressively during inhibin infusion to 26% of pretreatment levels (p < 0.05), whereas FSH levels in vehicle-infused controls were unchanged for several days and then rose (p < 0.05) to peak levels around menses. FSH levels did not change significantly during activin infusion into the CL. Although similar results were obtained in monkeys receiving peripheral or intraluteal infusions of inhibin, events following the peripheral infusion of activin were markedly different from those during intraluteal administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199270 TI - Platelet-activating factor acetylhydrolase activity in seminal plasma from the bull, stallion, rabbit, and rooster. AB - Platelet-activating factor (PAF) acetylhydrolase, which inactivates PAF, has been detected in human and bovine seminal plasma and may represent a mechanism for regulating sperm-derived PAF. This study was designed to characterize further PAF acetylhydrolase in seminal plasma from domestic animal species. Sperm-free seminal plasma from the bull, stallion, rabbit, and rooster was assayed for acetylhydrolase activity based on the release of [3H]acetate from PAF. As reported previously for bull seminal plasma, activity in stallion, rabbit, and rooster seminal plasma was linear with both time and protein concentration, with specific activities of 97.4, 1.2, and 0.33 nmol PAF hydrolyzed/mg protein/min, respectively. Activity in seminal plasma from the bull, rabbit, and rooster was calcium-independent whereas activity in stallion seminal plasma increased with added calcium (p < 0.01). Addition of EDTA partially inhibited acetylhydrolase activity in stallion seminal plasma but increased the specific activity in rabbit seminal plasma (p < 0.01). Enzyme activity in bull seminal plasma was nondialyzable (50,000 molecular weight cutoff), stable at pH 5.0, and heat-labile (> or = 60 degrees C). Very little activity was associated with bull seminal plasma lipoproteins isolated by KBr flotation or by precipitation with polyanions. These results demonstrate that PAF acetylhydrolase activity is present in seminal plasma from different species, with large differences in specific activity among species. These differences may be related to species differences in the physiological role of PAF and its regulation in sperm and male tract fluids. PMID- 8199269 TI - Kinematic response of human spermatozoa to nonoxynol-9. AB - This study was an examination of the dose response of the kinematics of human sperm motion to 1-min and 30-min incubations with the spermicide Nonoxynol-9 (N9). At concentrations resulting in only slight reductions in percentages of motile sperm (MOT), increasing N9 decreased the progressiveness of sperm motion (reflected in decreasing straight line velocity). This decline in progressiveness resulted from both decline in the vigor (reflected in decreasing curvilinear velocity; VCL) and disruption of the pattern (reflected in decreasing linearity; LIN) of such motion. Since, after the 1-min incubation, VCL declined only slightly for seminal sperm over this range of N9 concentrations, declines in sperm progressiveness were primarily due to decreases in LIN. For sperm collected from the pellet fraction from a Percoll gradient technique, however, VCL declined substantially even at low concentrations of spermicide. These Percoll-separated sperm were, on the other hand, less sensitive to N9 than seminal sperm in terms of the dose response of MOT. This added resistance may be attributed to selection or to environmental or physiological changes caused by Percoll separation. Responses in mean amplitude of lateral head displacement (ALH) to increasing N9 also differed for the two treatments, increasing on average for seminal sperm while decreasing on average for Percoll-separated sperm. PMID- 8199271 TI - Basal cells of the human epididymis--antigenic and ultrastructural similarities to tissue-fixed macrophages. AB - Very little is known about the basal cells in the epididymal epithelium. Their function is unclear, although they are present in all mammalian epididymides studied. The corpus epididymides from five patients undergoing castration because of prostatic carcinoma were fixed and processed for electron microscopy. Basal cells were characterized by a slightly heterochromatic nucleus with prominent nucleolus, pale round mitochondria, dispersed endoplasmic reticulum, and sparse Golgi apparatus; they were often rich in lipofuscin inclusions, possibly originating from principal cells. Some peritubular macrophages in close proximity to the epithelium were structurally similar to basal cells. Immunohistochemical staining revealed in the epididymides of another ten patients that the basal cells were recognized by the monoclonal antibody (mAb) 25F9 against mature, tissue-fixed macrophages but not by mAbs 27E10 or RM3/1, which were against activated macrophages usually found in acute or late inflammation, respectively. On the basis of the present findings, as a working hypothesis a scavenging role of the basal cells in a local immune defense mechanism is proposed, in which antigenic products (possibly of sperm degradation), taken up by the principal cells, would be phagocytosed by the basal cells. It could be inferred that when the basal cells are overloaded, they would leave the epithelium to be replenished by tissue-fixed macrophages. PMID- 8199272 TI - Purification and molecular cloning of bovine oviduct-specific glycoprotein. AB - A specific 85-97-kDa (95-kDa) glycoprotein was found in bovine oviductal tissue and fluid during the follicular phase. In this study, a 95-kDa bovine oviductal glycoprotein (95-kDa BOGP) was purified by wheat germ agglutinin affinity and Mono-Q ion-exchange column chromatography. The first 29 NH2-terminal amino acid residues were determined by gas-phase microsequencing. A cDNA expression library prepared from poly(A)+ RNA isolated from bovine oviducts was screened with a monoclonal antibody to 95-kDa BOGP. A single positive clone containing a approximately 2-kb cDNA insert was isolated. The coding region contained 1612 bp translating to 537 amino acids. The derived amino acid sequence contained a partial signal sequence of 18 amino acids followed by 29 amino acids that were identical to the NH2-terminal amino acids determined by protein sequencing of purified 95-kDa BOGP. The amino acid sequence predicted a mature protein of 519 amino acids (57,684 daltons) containing one potential N-linked glycosylation site and five cysteines. Northern blot hybridization with a digoxigenin-labeled probe indicated that a single message of approximately 2.5 kb was present in oviductal RNA, and this message was detected in significantly greater amounts in oviductal RNA during the follicular phase than during the luteal phase. The amino acid sequence of a portion of 95-kDa BOGP was highly homologous (71% identity) to that of a baboon oviduct-specific glycoprotein. PMID- 8199273 TI - Bovine inner cell mass cells as donor nuclei in the production of nuclear transfer embryos and calves. AB - Bovine inner cell mass (ICM) cells were used as donor nuclei in nuclear transfer procedures to determine their totipotency. ICMs were isolated by immunosurgery from expanded Day 7-9 blastocysts that had been produced in vitro. Each individual ICM cell was transferred into an enucleated oocyte. Oocytes were checked for enucleation with Hoechst dye to ensure that all DNA was removed, thus eliminating the possibility of parthenogenetic development. ICM cell-oocyte units were fused by a brief electrical pulse (110 V DC, 15 microseconds in a 500 microns chamber), and the resulting zygotes were placed into CR1 bovine embryo culture medium supplemented with amino acids and fetal calf serum. The nuclear transfer embryos were scored for development to the blastocyst stage on Day 7 (day of fusion = 0). A total of 948 nuclear transfers were completed in 25 trials. In 12 of the trials, development to the blastocyst stage (5%, 30 of 629) was observed. This resulted in an overall developmental rate of 3% for all trials. Twenty-six of the ICM-derived blastocysts were transferred. The initial pregnancy rate at 30 days was 23% with six pregnant recipients. Two pregnancies were lost after 60 days, and four calves were born, two of which were stillborn. These results demonstrated that nucleic of ICM cells from expanded bovine blastocysts were pluripotent, if not in fact totipotent, since these nuclei after nuclear transfer to enucleated oocytes could direct embryonic and fetal development resulting in live offspring. PMID- 8199274 TI - Follicle-stimulating hormone receptor expression in the rat ovary: increases during prepubertal development and regulation by the opposing actions of transforming growth factors beta and alpha. AB - Pituitary gonadotropin FSH acts exclusively on ovarian granulosa cells by binding to specific plasma membrane receptors. Transforming growth factors alpha and beta (TGF alpha and TGF beta), produced locally within the ovary, have been shown to regulate diverse follicle functions, although their potential role in the regulation of FSH receptors has not been assessed. Our first objective was to demonstrate developmental changes in the expression of FSH receptor gene and protein; we then analyzed the regulation of FSH receptor expression by TGF beta s and TGF alpha in cultured granulosa cells. Analysis of steady-state FSH receptor mRNA and protein levels in neonatal and prepubertal ovaries revealed the existence of two predominant FSH receptor mRNA transcripts, 7.0 and 2.5 kb in size, showing a dramatic increase between Day 15 and Day 18 of age followed by a plateau up to 27 days of age. A close parallelism in the developmental changes in FSH receptor mRNA levels and FSH receptor content was observed. Cultured granulosa cells obtained from estrogen-treated immature rats exhibited FSH receptor transcripts similar in size to those seen in whole ovaries. Treatment of granulosa cells for 48 h with TGF beta 1 increased the levels of FSH receptor mRNA for both the 7.0- and 2.5-kb transcripts in a dose-dependent manner (ED50, 1.5 ng/ml), with a maximal 4.0 +/- 0.8-fold increase over control levels observed in response to 10 ng/ml TGF beta 1. Also, TGF beta 2 was as potent as TGF beta 1 in increasing FSH receptor mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199275 TI - Corticotropin-releasing hormone effects on luteinizing hormone and cortisol secretion in intact female rhesus macaques. AB - It is generally accepted that corticotropin-releasing hormone (CRH) is the central mediator of stress-activated changes in the pituitary-adrenal axis because it results in the release of ACTH and ultimately increases the systemic levels of cortisol. And, because in some situations CRH also inhibits the hypothalamic release of GnRH, it has been presumed that it plays the central role in stress-related reduction in pituitary-gonadal function as well. We previously have shown that 6 h of restraint stress in intact female rhesus macaques suppresses plasma levels of LH in the follicular but not the luteal phase of the menstrual cycle and that this effect lasts beyond the period of restraint. Since CRH inhibits both the GnRH pulse generator and LH release in ovariectomized macaques and is generally thought to be the central mediator of stress-induced inhibition of gonadotropin release, we investigated the influence of CRH administration on LH in undisturbed intact female rhesus macaques. Blood samples were collected at 15-min intervals for 15 h from a remote site from female macaques in both the follicular and luteal phase. During this time, each animal received a 4-h infusion of CRH (100-micrograms bolus followed by 100 micrograms/h for 4 h) through an indwelling jugular catheter. Blood samples were collected for an additional 8 h after cessation of the CRH infusion. Cortisol levels were significantly elevated during and after the CRH infusion and were comparable to levels observed in animals that experienced restraint. However, CRH did not suppress LH levels in either the follicular or the luteal phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199276 TI - Synthesis of the allylic regulatory steroid, 3 alpha-hydroxy-4-pregnen-20-one, by rat granulosa cells and its regulation by gonadotropins. AB - The production of the allylic regulatory steroid 3 alpha-hydroxy-4-pregnen-20-one (3 alpha HP) in the rat ovary was examined and compared to progesterone levels through use of specific RIAs that had been validated by capillary gas chromatography-mass spectrometry (GC/MS). Results showed that serum levels of 3 alpha HP are comparable to levels of progesterone at all ages examined. In the 4 day cycling rat, serum levels of 3 alpha HP were highest during diestrus and lowest during proestrus and estrus, while serum FSH levels were highest during proestrus/estrus and lowest during diestrus. Hypophysectomy resulted in decreases in ovarian and serum 3 alpha HP. Treatment of hypophysectomized rats with eCG, but not hCG, increased ovarian and serum 3 alpha HP, while serum progesterone was elevated by treatment with hCG. Ovariectomy resulted in a 55-60% reduction in serum 3 alpha HP, indicating that ovaries are a substantial, but not exclusive, source of 3 alpha HP in serum. As further evidence, cultures of preparations consisting primarily of either granulosa cells or granulosa/theca "shells" produced 3 alpha HP in time-dependent amounts comparable to those of progesterone. Granulosa cells in culture showed a significant increase in accumulation of 3 alpha HP (and progesterone) due to treatment with FSH, but not LH. In contrast to the granulosa-only cell cultures, follicle shells consisting of theca and granulosa cells responded to either LH or FSH treatment with marked increases in 3 alpha HP; increases resulting from combined treatment (FSH + LH) were significantly greater than those due to each hormone alone, but the increases were not additives.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199277 TI - Photoperiodic synchronization of a circannual reproductive rhythm in sheep: identification of season-specific time cues. AB - Seasonal reproduction in the ewe is generated by an endogenous circannual rhythm of reproductive neuroendocrine activity. Exposure to as few as 70 days of photoperiodic information a year is sufficient to synchronize the rhythm. The present study was conducted to identify which portions of the photoperiodic cycle are utilized for synchronization. For this purpose, we used pinealectomized ewes that could not respond reproductively to changes in day length. Selected photoperiodic information was provided via infusion of melatonin, a hormone that provides the neuroendocrine code for day length in this species. Melatonin was delivered according to circadian patterns. The infusion patterns were tailored to mimic those of melatonin secretion in pineal-intact ewes during one of the four seasons: winter, spring, summer, or autumn. The infusions were provided for 90 days a year during each of the three years following pinealectomy. The ewes were ovariectomized and treated with constant-release Silastic capsules containing estradiol; reproductive neuroendocrine activity was monitored by measurement of serum concentrations of LH. In the absence of exogenous melatonin, most (19 of 24) pinealectomized controls exhibited circannual LH cycles that were not in synchrony, indicating that the rhythm was free-running. Melatonin synchronized the rhythm (such that the period was 365 days and the stages of the rhythm were both concurrent among animals and in appropriate phase with the geophysical year), but not all melatonin patterns were equally effective in this regard. The most effective melatonin patterns mimicked those of secretion during summer. Spring and autumn melatonin patterns were less effective, and winter melatonin patterns were ineffective. These results support the concept that there is a seasonal specificity with regard to the photoperiodic cues that synchronize the circannual rhythm of reproductive neuroendocrine activity in the ewe. The rhythm is synchronized most effectively by long-day photoperiodic cues perceived on or around the summer solstice. PMID- 8199278 TI - [A comparison of different respiratory gas-humidifier systems for the respiratory therapy of premature infants in incubators]. AB - OBJECTIVE: 7 humidifier systems for neonatology were subjected to a performance test in our laboratory. DESIGN: In 18 measurement combinations, flow (2,6,16 l/minute), respiratory gas temperature (34 and 37 degrees C) and incubator temperature (33, 35, 37 degrees C) were varied. RESULTS: In only 70.6% of 126 measurements the minimum international standard for the absolute humidity in the respiratory gas (30 mg H2O/l air) was achieved or exceeded. In 3 systems this level was not reached in 9 resp. 10 of 18 measurements. Only 1 device that functions according to the "membrane humidification" principle fulfills the requirements with regard to constant high air humidity. In 36 of 126 ( = 28.6%) measurement combinations the respiratory gas temperature near the endotracheal tube varied > 1 degrees C from the system temperature setpoint. CONCLUSION: No controlled clinical tests regarding the importance and long term effects of different levels in the inspiratory air are so far available for the ventilatory treatment of neonates. PMID- 8199279 TI - [The effect of nitroglycerin on ornipressin (POR 8)-induced systemic and cardiovascular circulatory changes. An animal experimental study]. AB - OBJECTIVE: Local infiltration of ornipressin (OR) is widely used to reduce intraoperative bleeding. However, OR can cause severe side effects including hypertension, deterioration of cardiac performance and coronary vasoconstriction. Suggestions for therapy of haemodynamic side effects of OR include the use of nitroglycerin (TNG). This experimental study was designed to investigate the influence of TNG on changes of systemic haemodynamics and coronary perfusion produced by i.v. administration of OR. METHODS: 16 anesthetized closed-chest mongrel dogs were studied. Anaesthesia was administered using N2O/O2 (FiO2: 0.33) and enflurane (1Vol%ET). Saline-filled catheters were used to measure intravascular pressures. Left ventricular pressure change (dP/dt) was monitored with a cathetertip manometer. Cardiac output (CO) was determined using thermodilution, myocardial blood flow (MBF) using a Pitot catheter. Baseline values were taken (control) followed by a bolus injection of 0.03 U/kg OR i.v. The dogs were randomly assigned to two groups. Group I (Gr.I) (n = 9) received OR only and group II (Gr.II) (n = 7) was treated by infusion of 4 mg/kg.min TNG 7 to 30 min after injection of OR. Haemodynamic and cardiovascular changes were measured for 60 min at fixed time intervals. RESULTS: In both groups (Gr.I; Gr.II) OR produced significant changes in systolic (APS) (+29%; +32%) and diastolic (APD) (+47%; +37%) aortic pressure, cardiac index (CI) (-33%; -33%), peripheral vascular resistance (TPR) (+116%); +104%), stroke volume index (SVI) ( 23%; -34%), ejection fraction (EF) (-29%; -29% endsystolic volume (ESV) (+39%; +45%) and left ventricular enddiastolic pressure (LVEDP) (+50%; +66%). Myocardial blood flow (MBF) was reduced by 30% and 29% respectively and coronary vascular resistance (CVR) was increased (+97%; +84%). Coronary venous O2 saturation (SO2cor) decreased to 19% and 20% resulting in high AVDO2cor. As compared to Gr.I the administration of TNG resulted in significant decreases of APS, APD, TPR, ESV and LVEDP close to control values. However, administration of TNG did not effect MBF, CVR, SO2cor and AVDO2cor. CONCLUSION: Systemic haemodynamic effects of OR include hypertension due to peripheral vasoconstriction and impaired cardiac performance resulting in reduced cardiac output with low EF, high ESV and LVEDP. Concomitantly, OR produces coronary constriction with a distinct fall in MBF. Thus, myocardial oxygen balance is impaired. With TNG peripheral vascular effects of OR can be abolished but there is no effect of TNG on OR-induced reduction of coronary blood flow. Therefore, use of TNG for treatment of cardiovascular complications following the administration of OR must be considered with extreme caution. PMID- 8199280 TI - [Succinylcholine can be dispensed with in anesthesia: Pro]. PMID- 8199281 TI - [Succinylcholine can be dispensed with in anesthesia: Contra]. PMID- 8199282 TI - [A historical vignette. Ether versus chloroform]. PMID- 8199283 TI - [Comment on the article by J. Hausdorger: "Regional anesthesia in children: Contra" AINS 27 (1992) 443-444]. PMID- 8199284 TI - [The computer in anesthesia--where do we stand today?]. PMID- 8199285 TI - [Succinylcholine: Quo vadis?]. PMID- 8199286 TI - [Expert systems in medicine: possible uses in anesthesia]. AB - The euphoric assumption that powerful computers fed with sophisticated software programmes may serve as a substitute for human knowledge and decision making has been replaced by a more realistic concept of how computers may help in collecting data and their interpretation on the basis of human knowledge and experience. The computer is now used as a dedicated tool to support man in overtaking cumbersome and monotonous processes and tedious calculations. Running 24 hours a day, a specific feature of the computer is that depending on unequivocal software programmes it does neither forget or alter commands and information. Computer programmes imitating human thinking and information processing are called expert or knowledge based systems. These are especially useful when multiple possible combinations of data make a given task very complex. This review presents several systems used in different medical disciplines to describe fundamental ideas, different problem-solving methods, techniques and possible working fields including anaesthesia. It is made clear why computers have found widespread use in all administrative areas. In contrast, no system comparable in potency has been developed for use in clinical medicine in spite of 25 years of research in expert systems. This review starts with a definition of expert knowledge and the appropriate transformation of this knowledge to the computer. In addition, a general survey about the structure of expert systems and a state of the art in some current problem solving methods is given. Additional aspects and restrictions including technical, psychological and legal problems which seem to be unimportant from the outside but are essential for the development of expert systems are presented. PMID- 8199287 TI - [Analgesia and hemodynamics under 8 mu/kg clonidine for pain therapy following major abdominal surgery]. AB - OBJECTIVE: To characterise the haemodynamic profile after epidural injection of high-dose clonidine for postoperative pain management and to establish recommendations for the therapy of haemodynamic instabilities. DESIGN: 20 patients with major surgery on pancreas, stomach or infrarenal aorta took part in the study. Anaesthesia was a combined epidural/inhalational regimen with bupivacaine 0.25%, enflurane, oxygen/nitrous oxide, fentanyl 0.1 mg and pancuronium. Postoperative analgesia consisted of morphine 50 micrograms/kg in 10 ml NaCl 0.9% for the first 12 postoperative hours; if pain > = 5 points on the VAS occurred after > 12 h postoperatively clonidine 8 micrograms/kg in 10 ml NaCl 0.9% was injected epidurally and the pain intensity (self-assessment by the patient using the visual analog scale) and circulation (invasive pressure monitoring, pulmonary artery catheter) was monitored for 60 minutes in ten minutes intervals. RESULTS: The reduction of the initial VAS score of 6 was 50% after 20 minutes and 100% after 60 minutes. We observed a significant decline in heart rate (87 +/- 11 (t0), 74 +/- 10 min-1 (t60)), mean arterial pressure (97 +/ 17 (t0), 72 +/- 15 mmHg (t60)) and cardiac output (8.7 +/- 1.3 (t0), 7.0 +/- 1.3 l.min-1 (t60)) (all p < 0.001) and no change of systemic vascular resistance. Filling pressures (CVP and PCWP) remained stable. In 9 patients the mean arterial pressure fell below 60 mmHg (always within the first 40 min); 6 of these patients responded to infusion of a colloid (500 ml of hydroxyethyl starch at > = 2 ml/kg.min) whereas the other 3 patients needed a bolus injection of a betamimetic catecholamine (theodrenaline/cafedrine, Akrinor). CONCLUSION: Epidural clonidine 8 micrograms/kg causes rapid and intense analgesia. Haemodynamic instability is a consequence of a drop in heart rate and has to be treated accordingly. The application of a pure vasopressor does not seem to be indicated taking in account the fact that the total peripheral resistance remains unchanged and in the normal range. PMID- 8199288 TI - Plasma-induced graft copolymerization of HEMA onto silicone rubber and TPX film improving rabbit corneal epithelial cell attachment and growth. AB - A poly(2-hydroxyethyl methacrylate) (pHEMA)-grafted polymer film was prepared by plasma-induced graft copolymerization onto an elastic material, silicone rubber, and a plastic material, poly(4-methyl-1-pentene) (TPX). The control, Ar plasma treated and pHEMA-grafted silicone rubber and TPX surfaces were characterized by ESCA, FTIR-ATR, SEM and contact angle techniques. ESCA verified the respective chemical shift of control and Ar plasma-treated films. The presence of the grafted pHEMA was also verified by ESCA. The introduction of pHEMA onto a hydrophobic support provided an adequate surface for rabbit corneal epithelium cell attachment and growth. Cell attachment and growth onto these surfaces were examined by light microscopy. Cell attachment onto the control and Ar plasma treated surfaces was negligible, while improved attachment and growth of rabbit corneal epithelium cells was demonstrated on the pHEMA-grafted polymeric surface. At 72 h, the pHEMA-grafted silicone rubber surface attached and grew more cells as compared with those on a pHEMA-grafted TPX surface. The pHEMA-grafted silicone rubber surface demonstrated a confluent cell layer after 72 h. PMID- 8199289 TI - Effect of the suture on the durability of bovine pericardium used in cardiac bioprostheses. AB - Our study of the different biomaterials used in the construction of biological cardiac prostheses has shown it to be of vital importance that the physical properties of the tissue and of the suture that anchors it to the rigid polymeric support are compatible. By means of dynamic tests, we have determined the fatigue curve in sutured bovine pericardial tissue, expressed by the equation log y = 1.27 +/- 0.18 (0.26 +/- 0.05) log t, where y is the initial fatigue stress (MPa) and t is the time (min) it takes to achieve permanent deformation of the tissue. By applying this correction, we determine a set of values for stress-time which, when compared with those obtained with a non-sutured sample, reveal a significant fall in this ratio and, thus, a decrease in the durability. The use of suture threads of lesser elasticity than the pericardium may play an important role in reducing the durability of the bioprosthesis constructed with these materials. PMID- 8199290 TI - Investigation of surface properties of some polymers by a thermodynamic and mechanical approach: possibility of predicting mucoadhesion and biocompatibility. AB - Mucoadhesive properties of several polymers, such as sodium alginate, hydroxypropylmethyl cellulose, scleroglucan, xanthan gum, polyacrylic acid (Carbopol), and poly co-(methyl vinyl ether-maleic anhydride) (Gantrez), have been investigated by comparing a thermodynamical and a mechanical approach. Surface properties of polymers in the dry state have been studied by contact angle measurements and thermodynamical parameters derived by using different equations. This tensile adhesive strength of polymers in hydration conditions was measured by a modified DuNoy tensiometer. Comparison of the two different approaches has allowed us to conclude that thermodynamical consideration on surface energy can be used to evaluate mucoadhesive properties of materials. Data obtained with the two methods yielded a good linear correlation. Calculation of surface free energy of the considered materials also allowed a prediction of the water-polymer interface free energy: biocompatibility, defined according to the minimal interfacial free energy concept, could consequently be evaluated. PMID- 8199291 TI - Characterization of calcium phosphate powders by ESCA and EDXA. AB - Calcium phosphate (CaP) materials can be well characterized by traditional methods such as wet chemistry and X-ray diffraction (XRD). These methods, however, offer limitations when non-destructive evaluation of CaP coatings on curved surfaces is required. Since the source powders for these coatings are generally commercially available CaP powders, careful characterization of the source powders may allow inferences to be made regarding the effects of plasma spraying on coating composition. Nine commercially available CaP powders were characterized by scanning electron microscopy, wet chemistry and XRD. These techniques showed that major differences exist between individual powders claiming to be hydroxyapatite. Analysis of these nine powders by electron spectroscopy for chemical analysis (ESCA) and energy dispersive X-ray analysis (EDXA) suggest that these techniques can provide the chemical composition of CaP in a non-destructive manner and thus may be of use in determining the composition of CaP in configurations (such as coatings on metal surfaces) not readily amenable to traditional methods. A calibration curve is required, however, to relate this surface chemical composition result to the material's bulk composition as determined by wet chemistry analysis. Errors of less than 10% can be obtained using ESCA and EDXA. These studies suggest that non-destructive chemical composition evaluation by EDXA and ESCA may also be applicable to CaP coatings. PMID- 8199292 TI - Preparation of a new nerve guide from a poly(L-lactide-co-6-caprolactone). AB - A copolymer of L-lactide and 6-caprolactone (50:50, w/w) was synthesized and characterized. The thermal behaviour of this material did not show any crystallinity for several months; only after more than 1 yr of aging at room temperature and, particularly, in the in vitro degradation tests did it partially crystallize. The values of tensile strength, percent elongation at break and elastic modulus were, respectively, 25 MPa, 490% and 3 MPa. Transparent, elastic nerve guides having inner diameter of 1.3 mm and wall thickness of 175 microns were prepared. PMID- 8199293 TI - Evaluation of the osteogenic potential of biomaterials implanted in the palatal connective tissue of miniature pigs using undecalcified sections. AB - Calcium phosphate or calcium carbonate biomaterials are widely used as bone substitutes in periodontal surgery. This study evaluates the osteogenic potential of five different alloplastic biomaterials implanted in the connective tissue of the palatal papilla in miniature pigs. A porous hydroxyapatite (PHA), a dense hydroxyapatite (DHA), a semi-porous hydroxyapatite (SPHA), a tricalcium phosphate (TCP) and a calcium carbonate natural coral (NC) were implanted in a tunnel in the palatal papillae of seven miniature pigs. Undecalcified sections were examined histologically at 1, 2, 3, 4, 8, 12 and 24 wk intervals. Resorbable materials (TCP and NC) were totally resorbed by 24 wk. DHA, PHA and HA showed very limited resorption, although there were multinucleated giant cells in contact with PHA and SPHA. There was no histologically detectable bone formation in contact with or near any of the biomaterials tested. However, several particles of NC, and sometimes of PHA, were surrounded by a dense, mineralized matrix. It is concluded that none of these biomaterials, in their presently available forms, has any bone inducing capacity. PMID- 8199294 TI - Analysis of the in vivo reactions of a bioactive glass in soft and hard tissue. AB - A bioactive glass, S53P4, was implanted as granules subcutaneously in muscles and connective tissue of rabbits, as well as in the mandibular bone of a sheep. After the implantation period of 2-3 months, cross-sections were prepared and studied by scanning electron microscopy and energy dispersive X-ray analysis. The glass reacted essentially in the same way in all types of tissue. The granules consisted of an unreacted core and a reacted layer with a silica-rich and calcium phosphate-rich zone. Large hydroxyapatite crystals were occasionally found on top of the calcium phosphate surface of the granules implanted in soft tissue. On the basis of elemental analysis of the reaction layers it was found that the release of calcium from inside the glass is sufficient to account for the formation of the calcium phosphate surface layer, whereas the release of phosphate from the glass is not sufficient. PMID- 8199295 TI - Meniscal substitution with a Teflon-periosteal composite graft: a rabbit experiment. AB - A Teflon-periosteal composite graft was used as a substitute for the medical rabbit meniscus and was followed for a 3 month period. The results were compared to joints with autotransplantation of the medial meniscus and to non-operated control knees. Joint in vitro mechanics were similar to the non-operated controls for both treatments. Macroscopically, all composite menisci had changed in shape and the graft was found as a small remnant at the capsular periphery with prolonged or detached attachments resulting in an insufficient coverage of the tibial plateau. Except for one case, the autografts had healed in, but showed, similar to the composite menisci, prolongation of the attachments and insufficient coverage of the tibial plateau. The femoral and tibial cartilage showed osteoarthritic changes after both treatments. Except for one specimen, the artificial material was covered and penetrated by fibrocytes, and was fixed to the capsule without gap formation; however, fibrochondrocytes were not seen. The biological coat was thin and Teflon particles extruded from the matrix in some specimens, which was reflected by synovitis with foreign body reaction. Knees with autografts had a similar low-grade synovitis without any foreign body reaction. The importance of the attachment sites as well as the normal material properties of the substitute is pointed out. PMID- 8199296 TI - Protein permeation through poly(vinyl alcohol) hydrogel membranes. AB - Hydrogel membranes were prepared by radiation and chemical cross-linking of poly(vinyl alcohol) (PVA) in aqueous solutions. Effects of PVA concentration, PVA molecular weight and radiation dose, as well as concentration of cross-linking agent, in the case of the chemical cross-linking procedure, on the permeation of insulin, albumin and immunoglobulin (IgG) through the membranes were investigated. Glucose permeation was also studied. The cross-linking density affected the size of the macromolecular mesh of the hydrogel network and thus the water content of the membrane responsible for the diffusion of the solutes. The diffusion coefficient linearly increased for all the solutes with increasing water content in the PVA hydrogels, indicating that diffusion occurs primarily through the water hydrating the polymer network. The permeability study showed that the water content as well as the mesh size had an influence on the diffusion of low molecular weight glucose and insulin. Although the diffusion of higher molecular weight solutes, such as albumin and IgG, was not so much affected by the mesh size of elaborated PVA hydrogel membranes, the diffusion of these proteins was very low. PMID- 8199297 TI - Microsomal and soluble epoxide hydrolases are members of the same family of C-X bond hydrolase enzymes. AB - Sequence alignments of mammalian microsomal (MEH) and soluble epoxide hydrolases (SEH) with bacterial haloalkane dehalogenase (HAD) and haloacetate dehalogenase (HAcD) together with structural and functional evidence suggest that these four enzymes are structurally and mechanistically related. The catalytic mechanism of HAD and MEH have been recently shown to involve an ester intermediate formed by alkylation of an active site carboxyl group. Very pronounced sequence similarities of regions of MEH, SEH, and HAcD with the active site of HAD suggest that all four enzymes belong to the same family of C-X bond hydrolases which involve an alkyl-enzyme intermediate. The catalytic triads (nucleophile-base acid) of MEH and SEH are proposed to be Asp226-His431-Asp352 and Asp333-His523 Asp495, respectively, on the basis of sequence alignments with HAD. Although compelling arguments, through sequence alignments, can be made for the assignment of the nucleophile-base pair of the triad, the identity of the acid residue (e.g., Asp352 and Asp495) is more speculative. The three-dimensional structures of both MEH and SEH are suggested to contain structural elements of the alpha/beta hydrolase fold. PMID- 8199298 TI - Synthesis of Fjord region diol epoxides as potential ultimate carcinogens of dibenzo[a,l]pyrene. AB - Dibenzo[a,l]pyrene (DB[a,l]P) is one of the strongest polynuclear aromatic hydrocarbon carcinogens known. This paper describes the synthesis of potential ultimate carcinogens of DB[a,l]P: anti- and syn-11,12-dihydroxy-13,14-epoxy 11,12,13,14- tetrahydroDB[a,l]P (DB-[a,l]P-11,12-diol-13,14-epoxides). The method employed is also useful for the preparation of key intermediates for the synthesis of 11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrobenzo-[g]chrysene (BgC-11,12-diol-13,14-epoxide). Photochemical cyclization of the appropriately substituted phenanthrylphenylethylenes provided 9-carbomethoxy-11-methoxyBgC (4) and 11-methoxyBgC (3). The former was converted by reduction, oxidation, one carbon chain extension, and cyclization to 11-methoxy DB[a,l]P (7). Compounds 3 and 7 were converted by hydrolysis and oxidation to BgC-11,12-dione (10) and DB[a,l]P-11,12-dione (11), respectively. The diones are the precursors for the synthesis of the corresponding diol epoxides. anti- and syn-DB-[a,l]P-11,12-diol 13,14-epoxides 13 and 14 were prepared in 38% and 55% yields, respectively, from 11. Both diol epoxides had predominantly pseudodiequatorial hydroxyl groups, as seen in other sterically hindered diol epoxides. PMID- 8199299 TI - Interactions of allergenic hydroperoxides with proteins: a radical mechanism? AB - 1-(1-Hydroperoxy-1-methylethyl)cyclohexene was synthesized as a model compound for the study of the interaction of 15-hydroperoxyabietic acid-like terpenes with proteins. Two related epoxides, 1-(1-hydroxy-1-methylethyl)-2 oxabicyclo[4.1.0]heptane and 2,2-dimethyl-1-oxaspiro-[2.5]octan-4-ol, were also prepared as reference materials. Treatment of the hydroperoxide with FeCl3 and N alpha-Ac-Cys-OMe led to the formation of the corresponding alcohol and of both epoxides. The allergenic activity of these compounds was tested in guinea pigs using the Freund's complete adjuvant test. The hydroperoxide was found to be a strong sensitizer while both epoxides were found to be inactive at the same doses. The generation of highly-reactive radicals in the epidermis could lead to the formation of antigenic structures, the first step of the allergic contact dermatitis mechanism. PMID- 8199300 TI - Characterization of benzo[a]pyrene anti-diol epoxide adducts to human histones. AB - Nuclei from human lymphoblast cells grown in culture were treated with [7-14C] (+/-)-r-7,t-8-dihydroxy-t-9,t-10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (anti BPDE), and the nucleosomal core histones were isolated for adduct studies by cryogenic fluorescence line narrowing spectroscopy. The four core histones H2A, H2B, H3, and H4 were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which yielded each histone free of contamination by the others. Further purification of histones H2A, H2B, and H4 by reversed-phase HPLC also yielded a tetrahydrotetrol of benzo[a]pyrene, indicating that these three histones had some labile adducts. No tetrol was observed upon purification of histone H3. Fluorescence emission spectra of the HPLC-purified histones recorded at 4K after vibronic excitation into the S1 state were generally similar. Fluorescence line-narrowed spectra of model compounds formed by reaction of anti BPDE with acetic acid, ethylenediamine, cysteamine, and histidine were also recorded. Only the spectra of the ethylenediamine adduct model matched consistently, at different excitation wavelengths, the spectra of the adducted histones. From this it is concluded that the stable human histone adducts of anti BPDE are formed by reaction with lysine residues and/or the amino groups of the N termini. PMID- 8199301 TI - The role of sulfation and/or acetylation in the metabolism of the cooked-food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Salmonella typhimurium and isolated rat hepatocytes. AB - Mutagenic activity of the cooked-food mutagen/carcinogen 2-amino-1-methyl-6 phenylimidazo-[4,5-b]pyridine (PhIP) is highly dependent upon cytochrome P450 activation to the N-hydroxylated intermediate. In the present study the bioactivation pathways of PhIP were investigated in Salmonella typhimurium and isolated rat hepatocyte preparations. In the Ames/S. typhimurium assay, the acetyltransferase and sulfotransferase enzyme inhibitors pentachlorophenol (PCP) and 2,6-dichloro-4-nitrophenol (DCNP) were used to modulate mutagenicity. DCNP, but not PCP, produced a concentration-dependent decrease in mutagenic activity of 2-(hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-hydroxy-PhIP). In rat hepatocyte preparations, PCP and DCNP, as well as the cytochrome P450 IA1 and IA2 inhibitor alpha-naphthoflavone (ANF), were used to modulate metabolite, protein adduct, and DNA adduct formation. Incubations of [3H]PhIP (100 microM) with Aroclor 1254-induced or uninduced hepatocytes resulted in the formation of several metabolites, including 4'-(2-amino-1-methylimidazo[4,5-b]pyrid-6 yl)phenyl sulfate (4'-PhIP-sulfate), 2-amino-1-methyl-4'-hydroxy-6- phenylimidazo[4,5-b]pyridine (4'-hydroxy-PhIP), a glucuronide conjugate of 2 (hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine, and other uncharacterized metabolites. While PCP or DCNP pretreatment produced a significant decline in sulfate-dependent conjugation of 4'-hydroxy-PhIP to 4'-PhIP-sulfate, these inhibitors produced only slight decreases in PhIP-dependent covalent binding to proteins in hepatocytes derived from either Aroclor 1254-induced or uninduced rats. PhIP DNA adduct levels were relatively unchanged by PCP or DCNP pretreatment of Aroclor 1254-induced hepatocytes. DNA adducts from hepatocytes dosed with N-hydroxy-PhIP, however, resulted in a decrease in adduct levels from cells pretreated with PCP or DCNP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199302 TI - Synthesis, structure, and properties of rac-2,3-dimercaptosuccinic acid, a potentially useful chelating agent for toxic metals. AB - rac-2,3-Dimercaptosuccinic acid (rac-DMSA) may be a more effective antidote for the treatment of heavy metal poisoning than meso-2,3-dimercaptosuccinic acid (meso-DMSA), which is used at present. A comparative study of these two chelating agents has been undertaken in order to investigate this possibility. The structures of rac-DMSA and the precursor in its synthesis, rac-2,3 bis(acetylthio)succinic acid, have been determined by single-crystal X-ray analysis and compared with the structures of the corresponding meso compounds. The concentration distributions of the various ionic and molecular species of rac DMSA that are present in aqueous solutions in the pH range 1.8-12.8 have been calculated from the four acid dissociation constants that have been determined potentiometrically at an ionic strength of 0.10. The conformations of these species in aqueous solutions have been determined by 1H NMR spectroscopy as a function of pH. The rac-DMSA exists in the crystal lattice as a double-stranded structure in which each molecule is in a gauche configuration. The meso-DMSA, however, exists in a single strand in which each molecule has adopted an anti configuration and the individual molecules are joined together at each end by hydrogen bonds. These differences in the conformations of rac- and meso-DMSA may account for the significant difference in the solubilities of the two compounds in aqueous solutions. In acidic solutions at elevated temperatures of about 95 degrees C, rac-DMSA is slowly but irreversibly converted to meso-DMSA. This conversion does not occur at ambient temperatures. PMID- 8199303 TI - Structure-mutagenicity and structure-cytotoxicity studies on bromine-containing cysteine S-conjugates and related compounds. AB - Glutathione and cysteine S-conjugates of several haloalkenes are nephrotoxic and cytotoxic. Chloroalkene-derived S-(1-chloroalkenyl)-L-cysteine conjugates, but not fluoroalkene-derived S-(2,2-dihalo-1,1-difluorethyl)-L-cysteine conjugates, are mutagenic in the Ames test, although both types of S-conjugates are cytotoxic and nephrotoxic. Recent studies showed that bromine-containing S-(2,2-dihalo-1,1 difluoroethyl)-L-cysteine conjugates are mutagenic in the Ames test, thus challenging the generalization that S-(2,2-dihalo-1,1-difluoroethyl)-L-cysteine conjugates are not mutagenic. Hence a series of bromine-containing and bromine lacking S-(2,2-dihalo-1,1-difluoroethyl)-L-cysteine conjugates was prepared, and their mutagenicity was assessed in the Ames test with Salmonella typhimurium TA2638 as the test strain. In addition, several indices of cytotoxicity, including cytotoxicity in LLC-PK1 cells, induction of Ca2+ release from pig kidney mitochondria, and DNA double-strand breaks in LLC-PK1 cells, were measured. The bromine-containing S-conjugates S-(2-bromo-2-chloro-1,1 difluoroethyl)-L- cysteine (BCD-FC), S-(2-bromo-1,1,2-trifluoroethyl)-L-cysteine (BTFC), and S-(2,2-dibromo-1,1-difluoroethyl)-L-cysteine (DBDFC) were mutagenic in the Ames test, whereas S-(2-chloro-1,1,2-trifluorethyl)-L-cysteine (CTFC), S (2,2-dichloro-1,1-difluoroethyl)-L-cysteine (DCDFC), and S-(1,1,2,2 tetrafluoroethyl)-L-cysteine (TFC), which lack bromine, were not. BCDFC, BTFC, CTFC, DBDFC, and TFC were cytotoxic in LLC-PK1 cells, and their cytotoxicity was blocked by the cysteine conjugate beta-lyase inhibitor (aminooxy)acetic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199304 TI - Inhibition of peroxidase-catalyzed reactions by arylamines: mechanism for the anti-thyroid action of sulfamethazine. AB - Sulfonamide antibiotics, typified by sulfamethazine (SMZ), are widely used in veterinary practice. Sulfonamide residues in milk and meat products are of regulatory concern since SMZ is a thyroid carcinogen in rodents and sulfonamide induced hypersensitivity reactions, including hypothyroidism, have been reported in humans. SMZ and other primary arylamines inhibited iodination reactions catalyzed by thyroid peroxidase (TPO) and the closely related lactoperoxidase (LPO). Inhibition of LPO-catalyzed triiodide ion formation by SMZ and other primary arylamines was complex as both apparent Km and Vmax values were affected, but consistent with a rapid equilibrium binding mechanism. The apparent Ki for SMZ inhibition of TPO- and LPO-catalyzed iodide ion oxidation was approximately 0.42 and 0.11 mM, respectively. The corresponding Ki values for a series of para substituted anilines correlated with the ease of one-electron N-oxidation as measured by ionization potentials determined from semiempirical molecular orbital calculations. The aniline derivatives containing electron-donating substituents (e.g., p-CH3, p-OEt, p-Cl) were converted by LPO to colored products characteristic of one-electron oxidation. However, sulfonamides were not consumed in such reactions nor were any N-oxygenated derivatives formed in the absence of ascorbate (e.g., hydroxylamino, nitroso, nitro, azoxy). These observations suggest that the primary mechanism for sulfonamide-induced hypothyroidism is reversible inhibition of TPO-mediated thyroid hormone synthesis and not the formation and covalent binding of reactive N-oxygenated metabolites. These results are consistent with a hormonal mechanism for SMZ-induced thyroid carcinogenesis mediated by thyroid-stimulating hormone (TSH).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199305 TI - Metabolism of the chlorofluorocarbon substitute 1,1-dichloro-2,2,2 trifluoroethane by rat and human liver microsomes: the role of cytochrome P450 2E1. AB - 1,1-Dichloro-2,2,2-trifluoroethane (HCFC-123) has been developed as a substitute for ozone-depleting chlorofluorocarbons. The atmospheric lifetime of HCFC-123 is expected to be much shorter than those of chlorofluorocarbons; however, due to its lower stability and the presence of carbon-hydrogen bonds, metabolism of HCFC 123 in mammals and metabolism-dependent toxicity is likely. We compared the metabolism of HCFC-123 and its analog halothane in rat and human liver microsomes. 19F-NMR studies showed that trifluoroacetic acid is a major metabolite of HCFC-123. Besides trifluoroacetic acid, chlorodifluoroacetic acid and inorganic fluoride were identified as products of the enzymatic oxidation of HCFC-123 in rat and human liver microsomes by 19F-NMR and mass spectrometry. The metabolites were not detected in incubations with halothane. HCFC-123 and halothane were transformed by liver microsomes from untreated rats at low rates. Microsomes from ethanol-and pyridine-treated rats metabolized both HCFC-123 and halothane at much higher rates. These microsomes also exhibited high rates of p nitrophenol oxidation. p-Nitrophenol is a model substrate mainly oxidized by P450 2E1 to p-nitrocatechol. Samples of human liver microsomes showed considerable differences in the extent of HCFC-123, p-nitrophenol oxidation, and chlorzoxazone hydroxylation. In human liver microsomes, rabbit anti-rat P450 2E1 IgG recognized a single protein band corresponding in apparent molecular weight to human P450 2E1. Immunoblot analysis revealed considerable heterogenity in the P450 2E1 protein content of the human liver samples. Trifluoroacetic acid formation from HCFC-123 and halothane and p-nitrocatechol formation from p-nitrophenol were significantly reduced by the P450 2E1 inhibitor diethyldithiocarbamate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199306 TI - Covalent binding of benzoquinone to reduced ribonuclease. Adduct structures and stoichiometry. AB - As a model for the reaction of chemically reactive quinone metabolites with cellular proteins in vivo, the reactions of benzoquinone (BQ; 1-64 mol/mol of protein) with bovine pancreatic ribonuclease A (RNase), reduced RNase, S (amidomethylated) reduced RNase, and reduced guanidinated RNase were investigated. The reaction stoichiometry and products were characterized by means of HPLC, UV-vis spectrophotometry, electrospray mass spectrometry, amino acid analysis, alkaline permethylation analysis, and measurement of the covalent binding of [14C]BQ to protein. Native RNase and S-(amidomethylated) reduced RNase show no reaction with BQ over 60 min at pH 7.4-9.6, whereas reduced RNase, which has 8 free SH groups/mol, reacts rapidly with exactly 24 molecules of BQ, of which 8 become covalently bound to protein-SH groups while 16 are reduced to hydroquinone. Half of the latter is formed via BQ oxidation of the initially formed S-(2,5-dihydroxyphenyl)cysteine moieties. Michael addition of a second protein nucleophile to each resulting S-(2,5-quinoyl)cysteine moiety, followed by reoxidation of that addition product by BQ, generates the second group of 8 molecules of HQ and results in cross-linking. Reduced guanidinated RNase, in which most of the lysines are blocked by guanidination with O-methylisourea, also reacts rapidly with BQ, but only ca. 16 equiv are consumed; of these, 8 become covalently bound to protein-SH groups while the others are reduced to HQ. Thus, even though the lysine residues in native RNase and S-(amidomethylated) reduced RNase do not react with BQ, they may react with (2,5-quinonyl)-S-protein moieties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199307 TI - Selective formation of oxindole- and formylkynurenine-type products from tryptophan and its peptides treated with a superoxide-generating system in the presence of iron(III)-EDTA: a possible involvement with iron-oxygen complex. AB - The oxygenation of tryptophan and its peptides by the superoxide-generating system hypoxanthine/xanthine oxidase in the presence of iron(III) and ethylenediaminetetraacetic acid (EDTA) has been investigated. The reaction of a tryptophan derivative, N-(tert-butoxycarbonyl)-L-tryptophan, with hypoxanthine/xanthine oxidase/Fe(III)-EDTA mainly resulted in the oxygenation of the pyrrole ring of the indole nucleus. 2-[(tert-Butoxycarbonyl)-amino]-3-(3 oxindolyl)propionic acid and N-(tert-butoxycarbonyl)-N'-formylkynurenine were identified as the major products. Similar oxindole- and formylkynurenine-type products were also obtained from the N-(tert-butoxycarbonyl) derivative of the tryptophan-containing peptides Ile-Trp, Trp-Leu, Gly-Trp-Leu, and Ala-Trp-Ile. In all cases, however, hydroxylation products of the benzene ring of the indole nucleus were scarcely detected, leading to the assumption that free hydroxyl radical did not play a role in the tryptophan oxidation of this system. Of interest was the fact that the reaction of N-(tert-butoxycarbonyl)-L-tryptophan with H2O2/horseradish peroxidase mainly afforded the same oxindole- and formylkynurenine-type products as those obtained in the hypoxanthine/xanthine oxidase/Fe(III)-EDTA system. Taken together, iron-oxygen complex-type active species may play a role in the tryptophan oxygenation in a superoxide-generating system in the presence of iron-EDTA. PMID- 8199308 TI - S-oxidative cleavage of farnesylcysteine and farnesylcysteine methyl ester by the flavin-containing monooxygenase. AB - Posttranslational modification of proteins with a farnesyl or geranylgeranyl group appears to be crucial in the signal transduction of eukaryotic cells. For example, farnesylation of ras-encoded proteins is a key process that apparently leads to membrane association of proteins that perform a function in cell growth promoting activity. Although it has been suggested that prenylation of proteins may be an important regulatory mechanism, little is known about the mechanism whereby prenylated proteins are removed from the membrane. In our previous report [(1992) Chem. Res. Toxicol. 5, 193-201], we showed that S-alkenylated cysteines and mercapturates of xenobiotics were S-oxygenated by the flavin-containing monooxygenase. The S-oxides were not indefinitely stable and rearranged or underwent elimination reactions that cleaved the C-S(O) bond. As a model for farnesylated proteins and peptides, the biotransformation of farnesylcysteine methyl ester was examined in the presence of pig liver microsomes. Two prominent products were formed: farnesyl methyl ester sulfoxide and farnesylcysteine, arising from the action of the flavin-containing monooxygenase and esterase of pig liver, respectively. Formation of farnesylcysteine methyl ester sulfoxide by the flavin-containing monooxygenase was stereoselective (i.e., 71.5%:28.5%, major to minor diastereomer) in good agreement with previously reported stereoselectivity studies of other related S-alkylcysteine-containing compounds. That the stereoselectivity observed was due to S-oxygenation of the sulfur atom was verified in parallel chemical oxidation studies by using micellar electrokinetic capillary chromatography. Farnesylcysteine methyl ester was an excellent substrate for the flavin-containing monooxygenase, and the S-oxide product was confirmed by HPLC electrospray mass spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199309 TI - Synthesis, characterization, and quantitation of the major adducts formed between sulfur mustard and DNA of calf thymus and human blood. AB - As part of a program to develop methods for verification of alleged exposure to sulfur mustard, we synthesized and characterized the adducts most likely formed by alkylation of DNA with sulfur mustard: N7-[2-[(2 hydroxyethyl)thio]ethyl]guanine (1), bis[2-(guanin-7-yl)ethyl] sulfide (2), N3-[2 [(2-hydroxyethyl)thio]ethyl]adenine (3), and O6-[2-[(2-hydroxyethyl)thio]ethyl] guanine and its 2'-deoxyguanosine derivative. Incubation of double-stranded calf thymus DNA and human blood with [35S]sulfur mustard in vitro followed by enzymatic degradation of the DNA and mild depurination afforded three major radioactive peaks upon HPLC analysis. These peaks were identified as 1-3 by coelution with the synthetic markers and mass spectrometric and electronic spectra. Compound 1 appeared to be the most abundant adduct, which is in agreement with previous investigations on DNA alkylation with sulfur mustard. PMID- 8199310 TI - Mechanism of formation of ethenoguanine adducts from 2-haloacetaldehydes: 13C labeling patterns with 2-bromoacetaldehyde. AB - The mechanism of formation of etheno (epsilon) adducts of nucleic acid bases from 2-haloacetaldehydes is generally assumed to occur via initial Schiff base formation resulting from reaction of the aldehyde with an exocyclic amine. We recently revised the 1H NMR assignments of the epsilon protons of 1,N2-epsilon Guo (Guengerich, F. P., Persmark, M. P., and Humphreys, W. G. (1993) Chem. Res. Toxicol. 6, 635-648). In that work we also observed a facile and specific exchange of H7 of 1,N2-epsilon-Guo and H5 of N2,3-epsilon-Gua with H2O. These findings raise questions about the mechanistic conclusions reached on the basis of labeling studies with deuterated ClCH2CHO (Sattsangi, P. D., Leonard, N. J., and Frihart, C. R. (1977) J. Org. Chem. 42, 3292-3296). BrCH2-13CHO was prepared from BrCH2(13)CO2H and used to prepare 1,N2-epsilon-Guo (from Guo) and O6-ethyl N2,3-epsilon-Gua (from O6-ethylGua). The positions of the labels were determined by 1H NMR spectroscopy experiments to be adjacent to the original Gua N2 (exocyclic) atom in both cases, i.e., at C6 in both epsilon products. The labeling patterns are consistent with a mechanism involving initial Schiff base formation from the N2 atom and the aldehyde and subsequent nucleophilic attack of an endocyclic nitrogen on the methylene carbon. PMID- 8199311 TI - Mutation and repair induced by the carcinogen 2-(hydroxyamino)-1-methyl-6 phenylimidazo[4,5-b]pyridine (N-OH-PhIP) in the dihydrofolate reductase gene of Chinese hamster ovary cells and conformational modeling of the dG-C8-PhIP adduct in DNA. AB - Three experiments using 20 microM 2-(hydroxyamino)-1-methyl-6-phenylimidazo[4,5 b]pyridine (N-OH-PhIP) were performed to induce mutations in the dihydrofolate reductase (DHFR) gene of a hemizygous Chinese hamster ovary (CHO) cell line (UA21). Metabolized forms of this chemical primarily bind at the C-8 position of guanine in DNA. In total, 21 independent induced mutants were isolated and 20 were characterized. DNA sequencing showed that the preferred mutation type found in 75% of the induced DHFR- clones was G.C-->T.A single and tandem double transversions. In addition to base substitutions, one mutant carried a-1 frameshift and another one had lost the entire locus by deletion. The induced changes affected purine targets on the nontranscribed strand of the gene in nearly all of the mutants sequenced (18/19). At the time that the first two experiments were performed, the initial adduct levels were quantitated in treated cells at the mutagenic dose by 32P-postlabeling. While the induced frequency of mutation was relatively low (approximately 5 x 10(-6), the adduct levels after a 1-h exposure of UA21 cells to 20 microM N-OH-PhIP were relatively high (13 adducts x 10(-6) nucleotides). This latter method was then employed to learn if the induced mutation frequency correlated with rapid overall genome repair of PhIP-DNA adducts. Total adduct levels, determined using DNA samples from treated cells collected after intervals of time, were reduced by about 50% after 6 h, and about 70% after 24 h. Since overall genome repair in CHO cells is relatively slow compared with preferential gene repair, the removal of dG-C8-PhIP adducts was apparently efficient. In order to better understand the mutational and repair results, we performed computational modeling to determine the lowest energy structure for the major dG-C8-PhIP adduct in a repetitively mutated duplex sequence opposite dA. Results of this analysis indicate that the PhIP-modified base resembles previous structural determinations of (deoxyguanosin-8-yl) aminofluorene; the carcinogen is in the B-DNA minor groove and its adopts a syn conformation mispaired with an anti A. The implications of this conformational distortion in DNA structure for damage recognition by cellular repair enzymes are discussed. PMID- 8199312 TI - Reaction of chromium(VI) with ascorbate produces chromium(V), chromium(IV), and carbon-based radicals. AB - Reaction of potassium dichromate with sodium ascorbate was studied by EPR spectroscopy at room temperature, in 0.10 M N-[2-hydroxyethyl]piperazine-N'-[2 ethanesulfonic acid] (HEPES), phosphate, cacodylate, and tris(hydroxymethyl)aminomethane hydrochloride (Tris.HCl) buffers at pH 7.0, in the presence of 0.10 M spin trap [5,5-dimethyl-1-pyrroline 1-oxide or 2-methyl-N (4-pyridinylmethylene)-2-propanamine N,N'-dioxide]. Chromium(V), ascorbate radical, CO2-, and other carbon-based spin trap-radical adducts were observed. Chromium(V), CO2-, and the carbon-based radicals were observed at low ratios of ascorbate to chromium, and ascorbate radical was observed at high ratios of ascorbate to chromium. The presence of Cr(IV) was detected indirectly by reaction with Mn(II) and a subsequent decrease in the Mn(II) EPR signal. More Cr(IV) was found for the higher reaction ratios of ascorbate to Cr(VI). The only buffer effect observed was a relative decrease of the Cr(V) signal in Tris.HCl vs HEPES, phosphate, and cacodylate buffers, no change in the radical adducts was observed. There was no evidence for reactive oxygen species an intermediates in this reaction. Addition of the singlet oxygen trap 2,2,6,6-tetramethyl-4-piperidone hydrochloride showed no 2,2,6,6-tetramethyl-1-piperidinyloxy radical formation. The Cr(V) species did not react with dioxygen, and dioxygen did not affect the formation of carbon-based radicals. A mechanism consistent with these observations is discussed. PMID- 8199313 TI - The mechanism of stimulation of NADPH oxidation during the mechanism-based inactivation of cytochrome P450 2B1 by N-methylcarbazole: redox cycling and DNA scission. AB - The oxidation rate of NADPH is markedly stimulated during the mechanism-based inactivation of cytochrome P450 2B1 by N-methylcarbazole (NMC) in a reconstituted system consisting of NADPH-cytochrome P450 reductase, cytochrome P450 and phospholipid. The stimulation of NADPH oxidation in this system is due to 1 hydroxy-N-methylcarbazole (1-OH-NMC), one of the major metabolites of NMC. The 1 OH-NMC is further metabolized in an NADPH-dependent manner by the reconstituted system or by purified NADPH-cytochrome P450 reductase to give a more polar metabolite which has been isolated by HPLC. The conversion of 1-OH-NMC to this product was inhibited by superoxide dismutase (SOD), and incubation of the 1-OH NMC with hypoxanthine-xanthine oxidase resulted in the formation of the same product, suggesting that the superoxide anion was involved in the metabolism of 1 OH-NMC by the reductase. Redox cycling activity during the metabolism of 1-OH-NMC by reductase has been demonstrated. The oxidation of NADPH by the reductase in the presence of 35 microM 1-OH-NMC was enhanced approximately 23-fold [240 nmol of NADPH oxidized/(min.nmol of reductase)] relative to control levels in the presence of 500 microM NMC [10.5 nmol/(min.nmol of reductase)]. 1-OH-NMC (35 microM) caused a 40-fold increase in the rate of formation of superoxide during its metabolism by reductase. The rapid rates of NADPH oxidation and superoxide formation were inhibited by the addition of reduced glutathione (GSH) to the reaction mixture. Neither SOD nor GSH inhibited the reductase activity directly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199314 TI - Conformation of amine-modified DNA: 2-aminofluorene- and 2-(acetylamino)fluorene modified deoxydinucleoside monophosphates with all possible nearest neighbors. A comparison of search and optimization methods. AB - Although a significant part of the replication fork exists as single-stranded DNA, little is known about the effect of carcinogens and mutagens on single strand conformation. Large-scale conformational searches with potential energy minimization, using the torsion angle space molecular mechanics program DUPLEX, were employed to explore the conformation of all 16 deoxydinucleoside monophosphates bearing 2-aminofluorene (AF) or 2-(acetylamino)fluorene (AAF) modification on guanine. We have thus examined the effect of 3' versus 5' modification, the presence or absence of the acetyl group, and the effect of four different neighbors in each case. The principal effect of the acetyl group appeared to be the destabilization of anti (and, to a lesser degree, borderline anti) conformations for modified guanine. This mattered little in the 5' substituted dimers, where one conformational type predominated in the low-energy structures for the adducts of both AAF and AF: It was right-handed, with syn guanine, imperfect base-base stacking, and fluorene to 3'-sugar contacts. Greater divergence was seen in the 3'-substituted series. The AAF-substituted 3'-adducts primarily displayed good base-fluorene stacking, with syn-guanine in contact with the 5'-sugar. The AF-substituted 3'-adducts displayed a variety of structures which included base-base and carcinogen-base stacked forms. Two novel forms were encountered [global minima for d(ApG-AF) and d(GpG-AF)], whose unusual structures suggest mutagenic capability. In order to address the multiple minimum problem, we conducted our searches of conformation space using two alternative optimization methods that also employ differing search strategies. We used the Powell algorithm, BOTM, with starting conformations that are selected combinations of rotamers, and the method of simulated annealing (SA), with random or arbitrary starting conformations. While both approaches were effective in defining the most important structures, SA was more successful than BOTM in locating the structures of lowest energy. PMID- 8199315 TI - Mechanism of aralkyl-DNA adduct formation from benzo[a]pyrene in vivo. AB - Three different pathways have been proposed for the metabolic activation of the ubiquitous polycyclic aromatic hydrocarbon, benzo[a]pyrene (BP). The most widely accepted activation mechanism is based on ring oxidation to diol epoxides; the other two relatively less studied pathways involve radical cation formation and benzylic electrophilic ester formation arising from a chain of substitution reactions. The present study was undertaken to test for the existence of the latter mechanism in vivo. Female Sprague-Dawley weanling rats were injected subcutaneously with 320 mumol of BP/kg body weight, and the formation of DNA adducts was examined. 32P-Postlabeling analysis of the subcutaneous tissue DNA under newly developed chromatography conditions exhibited two sets of adduct profiles: one resulting from alkyl substitution and the other from ring oxidation. One major and two minor aralkyl-DNA adducts were detected. The relative adduct labeling (adducts/10(10) nucleotides) remained constant at around 2 during the first 5 days of treatment and then increased to 6.4 +/- 2.6 at day 7. The corresponding total values of the known ring oxidation (e.g., diol epoxide) adducts were 15-50 times higher. When animals were injected with 6 methyl-BP, 6-(hydroxymethyl)-BP, and 6-(acetoxymethyl)-BP, the known or proposed intermediates in the benzylic ester pathway, each of these and the parent compound showed chromatographically identical profiles of aralkyl-DNA adducts. Cochromatography in multiple solvents of these in vivo adducts with standards prepared by reaction of 6-(bromomethyl)-BP with individual nucleotides showed that the predominant in vivo aralkyl-DNA adduct was derived from guanine while the second major adduct was from adenine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199316 TI - Contact allergy to resin acid hydroperoxides. Hapten binding via free radicals and epoxides. AB - For a better understanding of the mechanisms of contact allergic reactions, the patterns of cross-reactivity between different resin acid oxidation products were studied. The 13,14(alpha)-epoxide and the 13,14(beta)-epoxide of abietic acid and 15-hydroperoxydehydroabietic acid (15-HPDA) were shown in experimental sensitization studies to be contact allergens. Cross-reactivity was observed between the alpha- and beta-epoxides and also between the epoxides and the previously identified rosin allergen 15-hydroperoxyabietic acid (15-HPA). This indicates that 15-HPA may form an epoxide which then reacts with skin protein to generate the complete antigen. 15-HPA and 15-HPDA cross-reacted as well. This can be explained by the formation of similar alkoxy radicals from both hydroperoxides which further react with skin protein. Cross-reactivity patterns of the resin acid oxidation products indicate that 15-HPA may react with skin proteins either as a radical or as an epoxide, thus generating different antigens. The presence in rosin of the epoxides of abietic acid was also studied. The beta-epoxide was detected in gum rosin. Moreover, the epoxides elicited reactions in rosin allergic individuals. Thus, the 13,14(beta)-epoxide of abietic acid was identified as a new, important rosin allergen. PMID- 8199317 TI - Hemoglobin binding of nitroarenes and quantitative structure-activity relationships. AB - Nitroarenes are important intermediates in industrial manufacturing and are found as environmental pollutants. Reduction of the nitro group to yield nitro radical anions, nitrosoarenes, and N-hydroxyarylamines is a crucial metabolic step for the genotoxic and cytotoxic properties of nitroarenes. N-Hydroxyarylamines can form adducts with DNA, with tissue proteins, and with the blood proteins: albumin and hemoglobin. The determination of hemoglobin adducts is an established method for biomonitoring populations exposed to aromatic amines. We determined the hemoglobin binding index (HBI) [(mmol compound/mol Hb)/(mmol compound/kg body weight)] of several nitroarenes in female Wistar rats. The logarithm of hemoglobin binding (log HBI) was plotted against several physicochemical parameters and against calculated electronic descriptors of nitroarenes. Most nitroarenes form hydrolyzable (e.g. sulphinamide) adducts with hemoglobin in rats. The extent of hemoglobin binding of nitroarenes increases with the reducibility of the nitro group, except for a few outliers. The structure activity relationships (SARs) for hemoglobin binding of nitroarenes and arylamines are similar. The SARs found for hemoglobin binding were comparable to the SARs found in the literature for mutagenicity and cytotoxicity of nitroarenes. In general cytotoxicity in rat hepatocytes, hemoglobin binding in rats and mutagenicity in Salmonella typhimurium increase with reducibility of the nitro group. Insufficient data are available to establish a SAR for the carcinogenicity of nitroarenes. PMID- 8199318 TI - Interspecific somatic hybrid of Ichang papeda with Valencia orange. AB - Protoplasts from the leaf of Ichang papeda (Citrus ichangensis Swingle) were fused with the protoplasts of embryogenic suspension culture of Valencia orange (Citrus sinensis Osbeck) in vitro by polyethylene glycol (PEG)-induced fusion. The regenerated embryoids were malformed and were transferred onto shoot induction medium. The shoots were then grafted on 15-day-old seedlings of trifoliate orange in vitro. Chromosome counts of the young leaves showed that the parents were diploids, 2n = 2x = 18, and the regenerated plants were tetraploids, 2n = 4x = 36. Peroxidase and glutamate oxaloacetate transaminase isozyme analysis confirmed that these tetraploids were somatic hybrids. They have the bands of both parents. The hybrid plants grew vigorously after transplanted into soil. Leaf morphology of the hybrid was similar to that of sweet orange. PMID- 8199319 TI - Modeling of the last stage of production phase of oxytetracycline fermentation processes. AB - In an attempt to disclose the reason why, during the last stage of FBOFP (fed batch oxytetracycline fermentation processes) its specific production rate in general decreases notably, the authors started with the modeling of the process based on operation data, and thus reached the conclusion that this is due to too low residual nitrogen in the substrate. This inference is quite unacceptable to the current practice of the process operations. It was finally realized that the trouble lies in that our old measurement method of residual nitrogen is misleading. Upon using improved measuring method, it was found that while the total residual nitrogen is plentiful, the available nitrogen notably decreases with time, and thus confirmed the authors' conclusions. Experiments on industrial fermentators showed that the product can be increased by 1%, and the titer reaches 3200 micrograms/ml. PMID- 8199320 TI - A domestic cell bioreactor and its application in virus culture. AB - A cell culture bioreactor (CellCul-20) and its application in cell and virus culture are described in this paper. It has been evaluated with strict aseptic tests and one-year's operation shown that CellCul-20 bioreactor can keep its aseptic condition after being autoclaved. It can meet the requirement for the control of the main parameters for cell and virus culture and the finely adjustment of the main parameters to meet the changing conditions of the cultivation. A high cell density and a high level of virus titre were reached respectively for Vero cells and Japanese encephalitis virus (JEV) while they were cultured in this bioreactor. It is the first report on large-scale culture of JEV infected Vero cells to prepare primary JEV vaccine. Some suggestions are made for the improvement of CellCul-20. PMID- 8199321 TI - Studies on caproic acid fermentation using immobilized cells. AB - Five carriers were tested for immobilizing caproic acid bacteria. The batch experiment results showed that the calcium alginate was the best one of the five immobilized materials. The characteristics of immobilized caproic acid bacteria cells were evaluated using a standard batch fermentation procedure. In the laboratory-scale experiments, the alginate beads could be maintained at least for 8 months with the yield of the caproic acid level about 11 mg/ml. Under optimum conditions, a maximum yield of caproic acid about 15 mg/ml could be obtained. The observed productive acid rate and its yield of immobilized cells appeared to be greater than that of the corresponding free cells suspension. The cell number per volume of immobilized cells was about ten times that of free cells. PMID- 8199322 TI - The cloning and sequencing of coat protein gene from beet necrotic yellow vein virus. AB - The beet necrotic yellow vein virus (BNYVV) isolate NM was isolated from sugarbeet infected with rhizomania in Inner Mongolia of China. The cDNA of BNYVV coat protein (CP) gene was amplified from the extracted RNA of BNYVV isolate NM by using the polymerase chain reaction (PCR) and cloned into pGEM-7zf(+). Its complete nucleotide sequence was determined by means of Sanger's dideoxy-mediated chain-termination method. The result shows that CP gene of BNYVV isolate has 567 nucleotides. It shares 98.8% and 96.7% identity with the CP gene of isolate F13 (report in reference [1]) in terms of amino acid and nucleotide sequence, respectively. PMID- 8199323 TI - Expression of a fusion protein containing calf prochymosin B(1-161) and human proinsulin. AB - The plasmid pJG202 containing Tac promoter, calf prochymosin B(1-161) gene and human proinsulin gene was constructed and transformed into E. coli JM105. The expression of the fusion protein consisting of 249 amino acids was controlled by IPTG and temperature, and the expressed protein was estimated to be 20-35% of the total cellular proteins by scanning of the SDS-PAGE gel stained with Coomassie brilliant blue R250. After CNBr cleavage, sulfitolysis, partial separation of the S-sulfonated human proinsulin and recombination of the disulfide bonds, human proinsulin with native properties, as evidenced by amino acid composition analysis, receptor binding and radioimmunoassays, could be obtained. PMID- 8199324 TI - Amplification and analysis of a male-specific SRY homologous sequence of cattle. AB - Based on the highly conserved region of human, rabbit and mouse SRY (sex determining region Y) sequences, primers were designed for the amplification of the unknown homologous sequence of cattle by polymerase chain reaction (PCR). A 200-bp male-specific amplifying fragment was obtained. The fragment shares high homology with the known SRY gene. By using the cloned fragment as a probe to hybridize to the Southern blot of HindIII-digested cattle genomic DNA, a 1.7-kb male-specific fragment was detected, which is considered to contain the 200-bp fragment. When the same pair of primers was used in amplification of human and goat DNA samples, the 200-bp male-specific fragment could be detected. PMID- 8199325 TI - Evidence of the specific molecular interactions between naringenin, NODD and nod promoter. AB - This paper presents evidence that specific molecular interactions occur between three nod regulation elements: naringenin, NODD and nod-promoter. No such interactions were observed when the concentration of naringenin was less than 0.4 mM. However, remarkable molecular interactions were observed when naringenin was at 4.0 mM. The interactions were highly specific because no such interactions have been observed when naringenin was exposed at various concentrations to other promoter-regulatory protein system (e.g., the protease regulatory system of Xanthomonas campestris, although, like NODD-nod-promoter system, specific binding occurs between the protease promoter and the corresponding regulatory protein). PMID- 8199326 TI - Synthesis, cloning and sequencing of glucoamylase cDNA from Aspergillus niger mutant T21. AB - Poly(A)+ RNA was isolated from Aspergillus niger T21, a glucoamylase overproducing strain and was used as template to synthesize double stranded cDNA. A cDNA library was then constructed. The E. coli transformants were screened for the glucoamylase cDNA by in situ colony hybridization with P-labeled fragment of glucoamylase gene as probe. The positive rate was 1.6%. Restriction analysis proved that 32% of the positive clones carried the inserts of 2.1 kb of full length glucoamylase cDNA. Sequence of the glucoamylase cDNA was determined and the result showed that the sequence of glucoamylase gene of the mutant T21 was almost the same as that reported previously. The high rate of glucoamylase cDNA containing clones in the cDNA library of strain T21 provided evidence of high steady state level of glucoamylase mRNA in mycelium of mutant T21. Most likely it is one of the major causes for the high glucoamylase productivity of mutant T21. PMID- 8199328 TI - Nursing education: increased enrollment in and graduation from degree programs. PMID- 8199327 TI - Cloning of human prourokinase cDNA without the signal peptide and expression in Escherichia coli. AB - Human prourokinase (pro-UK) cDNA without the signal peptide was obtained using synthetic oligonucleotide and DNA recombination techniques and was successfully expressed in E. coli. The plasmid pMMUK which contained pro-UK cDNA (including both the entire coding sequence and the sequence for signal peptide) was digested with Hind III and PstI, so that the N-terminal 371-bp fragment could be recovered. A 304-bp fragment was collected from the 371-bp fragment after partial digestion with Fnu4HI in order to remove the signal peptide sequence. An intermediate plasmid was formed after this 304-bp fragment and the synthetic oligonucleotide was ligated with pUC18. Correctness of the ligation was confirmed by enzyme digestion and sequencing. By joining the PstI-PstI fragment of pro-UK to the plasmid we obtained the final plasmid which contained the entire coding sequence of pro-UK without the signal peptide. The coding sequence with correct orientation was inserted into pBV220 under the control of the temperature-induced promoter PRPL, and mature pro-UK was expressed in E. coli at 42 degrees C. Both sonicated supernatant and inclusion bodies of the bacterial host JM101 showed positive results by ELISA and FAPA assays. After renaturation, the biological activity of the expressed product was increased from 500-1000IU/L to about 60,000IU/L. The bacterial pro-UK showed a molecular weight of about 47,000 daltons by Western blot analysis. It can be completely inhibited by UK antiserum but not by t-PA antiserum nor by normal rabbit serum. PMID- 8199329 TI - An overview of health care systems: Canada and selected OECD countries. AB - This article presents an overview of health care systems in Canada and selected OECD countries (Australia, France, Finland, Germany, Sweden, the United States and the United Kingdom). The article discusses the organization of health care systems, health care expenditure, the availability and utilization of health services, and the health status of the population. In addition, it highlights and compares key health care indicators that are common to all health care systems. The article focuses on the relationship between health expenditure and health status in terms of life expectancy and infant mortality and shows that the United States had the highest infant mortality and second lowest life expectancy for females at birth in 1990 while it spent the most on health care as percentage of GDP. The article also shows that the overall health status indicators in some countries such as Finland and Sweden are comparable to that of Canada despite spending considerably less on health care. PMID- 8199330 TI - The Canadian Birth Data Base: a new research tool to study reproductive outcomes. AB - A new tool for epidemiological, demographic, and genetic research--the Canadian Birth Data Base-is being developed at Statistics Canada. Over a million live birth and stillbirth records for the period 1987-89 received from all provincial and territorial offices of vital statistics are being processed in a form suitable for linkage with other files. Maternal, child health, occupational, and environmental concerns, as well as some of the consequences and possible risks involved in new reproductive technologies, could be investigated. Associations between socio-economic indicators (e.g., parental income, education, and occupation) and unfavourable birth outcomes could also be studied in the future. Approved statistical studies can be carried out within Statistics Canada on a cost-recovery basis. It is planned to update the data base annually. PMID- 8199331 TI - An update of an epidemiology study at a hydrometallurgical nickel refinery in Fort Saskatchewan, Alberta. AB - A five-year extension to an ongoing epidemiology study has been undertaken. Mortality information was updated for an additional five years through 1985-1989 for 715 male hydrometallurgical nickel refinery employees who worked at Sherritt Gordon Limited in Fort Saskatchewan, Alberta, during the years 1954 to 1978. Mortality ascertainment was obtained using the Canadian Mortality Data Base, maintained by Statistics Canada, and covered the years 1954 through 1989. Cause specific mortality analyses were accomplished for males, by age group and calendar year of death, for Canada and the province of Alberta. Total mortality was significantly below expectation (42 observed vs. 70 expected deaths for Canada, and 66 expected for Alberta). Statistically fewer observed deaths were found for circulatory disease while multiple myeloma and lymphoid malignancies demonstrated a statistically significant increase of observed deaths. Specific focus was directed at cancers of the respiratory system because of previous reports linking these conditions with exposure to nickel compounds in some workforces. No deaths due to nasal cavity or paranasal sinus cancer were detected among cohort or study group members. Four lung cancer deaths were found with five deaths expected for Canada and four expected for Alberta. To date, no association between exposure to nickel concentrate or metallic nickel and the subsequent development of respiratory cancer has been found in this study. The hydrometallurgical refinery operation is an enclosed process in contrast to other refinery processes such as pyrometallurgical and electrolytic. PMID- 8199332 TI - Medical procedure classification in Canada--where are we going? AB - Various medical procedure classifications have been used in combination with disease classifications in Canada for decades. In anticipation of the introduction of the next revision of the International Classification of Diseases (ICD-10), a project has begun to revise the Canadian Classification of Diagnostic, Therapeutic, and Surgical Procedures (CCP) that will accompany it. Changes in health care delivery dictate that this revised classification have broader application than its predecessor. This report begins with some results of the consultation processes undertaken to prepare for the revision. The planned structure and scope of the revised classification system are explained. Progress of the revision project to date and its future directions are described. The report's authors solicit information and assistance from classification users and from potential users of data based on the classification. PMID- 8199333 TI - The National Longitudinal Survey of Children (NLSC). AB - A National Longitudinal Survey of Children (NLSC) is being developed for implementation across Canada in 1994. A description is given of the objectives, plans and current status of the survey. The current assumptions concerning the survey methodology are also outlined along with an early indication of the content. PMID- 8199334 TI - Adult day care centres in British Columbia: client characteristics, reasons for referral and reasons for non-attendance. AB - This paper discusses a 1989 study of new admissions to 22 adult day care centres in British Columbia and compares it to similar studies in the U.S. The B.C. study investigated clients' characteristics, reasons for referral to the centres, and why some referrals did not attend. Of the new admissions, 63% were female and 30% lived alone. Compared to those in American studies, B.C. clients were older and more likely to live with a spouse. The primary medical conditions of B.C. clients were related to diseases of the circulatory system. As for daily activities, 58% could not bathe without supervision and 43% required assistance with dressing. Some 37% were unable to prepare their own meals; 31% needed help with housekeeping and 62% with shopping. The proportion of clients with mental diseases (38%) was similar to that in American adult day care centres. The three most common reasons for referring clients to adult day care centres were: to assist those who were socially isolated; to give family caregivers some respite; and to give clients emotional help. Perceptions varied as to why referred clients did not attend: for continuing care staff there were psychosocial factors; for adult day care staff it was related to characteristics of the service delivery system; and clients themselves cited functional, physical and operational factors (e.g., problems related to hearing and vision, transportation or physical barriers). PMID- 8199335 TI - Increase of the brain uptake index for L-ornithine in rats with hepatic encephalopathy. AB - We measured the brain uptake index (BUI) for radiolabelled L-ornithine (ORN) in rats with acute hepatic encephalopathy (HE) induced by two (onset stage) or three (comatous stage) administrations of a hepatotoxin-thioacetamide (TAA). In the comatose group, an increase of the BUI to 275% of control was measured at 24 h post-treatment. In the onset group, the BUI for ORN increased gradually with time: it reached 220% of control at 7 days post-treatment and 442% of control at 21 days post-treatment. HE did not raise the BUI for a blood-brain barrier (BBB) non-penetrable amino acid L-aspartate (ASP), indicating that HE activates ORN transport but does not produce BBB leakage. ORN transport through BBB was not increased in rats with hyperammonemia comparable to that accompanying HE, but was induced without liver damage. Considering recent evidence that ORN acting intracerebrally ameliorates pathophysiological symptoms of HE, increased transport ORN across BBB should facilitate HE therapy based on systemic administration of this amino acid. PMID- 8199336 TI - Striatal synaptophysin expression and haloperidol-induced synaptic plasticity. AB - Synaptophysin is a presynaptic vesicle protein and a marker of synaptic density. We have studied the expression of its encoding mRNA in the brains of rats treated with haloperidol (2 mg kg-1 d-1) for two weeks. A significant increase in synaptophysin mRNA content was observed in the dorsolateral striatum but not in other brain areas compared with control animals. A similar trend was observed for synaptophysin immunoreactivity. Quantification of synaptophysin mRNA per cell showed that the increase was pronounced in large putatively cholinergic, striatal neurones. These data provide further evidence that localized synaptic plasticity occurs after neuroleptic treatment and indicate that such alterations are manifested in terms of expression of a synaptic protein gene by striatal neurones. PMID- 8199337 TI - Effects of lidocaine on hippocampal pyramidal cells: depression of repetitive firing. AB - The effects of lidocaine on repetitive firing of the CA1 pyramidal cells were studied in the hippocampal slice preparation using conventional intracellular recording technique. The cells were activated by injecting depolarizing current through the recording microelectrode. Lidocaine (50 microM) diminished the repetitive firing and progressively reduced the maximal rate of rise of the successive action potentials. The firing produced by low currents was little affected but that produced by high currents was substantially depressed. The maximal rate of rise of successive action potentials produced by a train of short depolarizing pulses was also progressively reduced, especially at high frequency (100 Hz) of activation. These findings suggest that, in the hippocampal pyramidal cells, lidocaine causes a use-dependent depression of the Na+ current. This action may be responsible for the anticonvulsant effects of lidocaine since it occurred at a clinically relevant concentration. PMID- 8199338 TI - Patterned neural activity in brain stem auditory areas of a prehearing mammal, the tammar wallaby (Macropus eugenii). AB - Is patterned neural activity in immature, prefunctioning sensory systems a general phenomenon? Such patterning has been found in the prenatal visual and somatosensory systems. We have now identified patterning in the immature auditory system of a prehearing mammal, the tammar wallaby. Neurones recorded in vivo from the eighth nerve and cochlear nucleus at pouch days 94-122 discharged in bursts with rhythmic inter-spike intervals. Our findings are applied to the argument that neural activity is vital to sensory development. PMID- 8199339 TI - Distinct neurotrophic responses of axotomized motor neurons to BDNF and CNTF in adult rats. AB - In adult mammals, transection of the hypoglossal nerve results in a dramatic loss of choline acetyltransferase (ChAT) in the hypoglossal motor neurons without affecting their cell number. This injury-induced reduction in ChAT is prevented when brain-derived neurotrophic factor (BDNF) is applied to the proximal end of the transected nerve. In contrast, application of ciliary neurotrophic factor (CNTF) has no such effect, even though both factors are known to rescue developing motor neurons from cell death. These results suggest that BDNF may regulate the phenotypic expression of ChAT in mature motor neurons, and indicate that the sensitivity and response of motor neurons to such neurotrophic agents change with development. PMID- 8199340 TI - Increased trkB mRNA expression by axotomized motoneurones. AB - It has been previously demonstrated that members of the neurotrophin family may prevent death of motoneurones following axotomy. Here we report that the expression of mRNA for full-length trkB, which is a signal transducing receptor for BDNF and NT-4, increases transiently in spinal motoneurones after axotomy in adult rats. Thus, transection of the sciatic nerve resulted in markedly increased levels of trkB mRNA in axotomized motoneurones three days postinjury, while the levels had returned to normal within three weeks. The data support that neurotrophins may be important for survival and/or regeneration of motoneurones after axon lesion. PMID- 8199341 TI - Noninvasive detection of cerebral plasticity in adult human somatosensory cortex. AB - After upper limb deafferentation, adult macaques exhibit substantial reorganization of cortical somatosensory topography with enlargement of cortical areas responsive to facial stimuli. In the present study non-invasive magnetic source imaging technology has been used to map in detail the bilateral somatosensory homunculi in four neurologically normal controls and two upper arm amputees. Bilateral homuncular maps of normals and of the unaffected hemisphere of both amputees showed a wide hand area. The affected hemisphere of both amputees showed marked intrusion of facial representations into the digit and hand area consistent with the earlier observations in macaques. Our findings provide the first evidence of massive somatosensory plasticity in human adults and suggest a mechanism for post-amputation perceptual changes. PMID- 8199342 TI - Sparing of NADPH-diaphorase striatal neurons in Parkinson's and Alzheimer's diseases. AB - The free radical neuromodulator, nitric oxide (NO) has been implicated as a neurotoxin. Neurons containing NO synthase (NOS) also contain NADPH-diaphorase (NADPH-d) and are resistant to NO toxicity. We report that NADPH-d-containing neurons within the striatum are spared in patients with Parkinson's (PD) and Alzheimer's disease (AD). However, a number of these neurons in both diseases appeared shrunken or bulbous with foreshortened dendritic processes. Quantitative analysis of cell areas revealed a significant difference only in the size of putamenal AD neurons which were decreased compared to normal controls. The possible involvement of NO in the neuropathogenesis of striatal derangement is discussed. PMID- 8199343 TI - Event-related potentials demonstrate a narrow focus of auditory spatial attention. AB - The distribution of spatial attention across neighbouring sound sources was investigated by assessing event-related potentials (ERPs) to tone probes embedded in natural speech during a selective-attention task. Concurrent speech messages were delivered from the middle positions of two groups of three sound sources in free-field in front of the subject, one to the left and the other to the right of the midline. In each group, the two extreme neighbour loudspeakers were positioned very closely to the middle ones. Brief tone pips were delivered from all locations in a random order. ERPs elicited by the tone probes used to probe the extent of spatial attention showed its narrow focus, one comparable to that suggested by behavioural studies. PMID- 8199344 TI - Trypanosomes cause dysregulation of c-fos expression in the rat suprachiasmatic nucleus. AB - Rats infected with the parasite Trypanosoma brucei brucei showed selective changes of c-fos expression in the suprachiasmatic nucleus of the hypothalamus (SCN) during spontaneous sleep (S) and wakefulness (W) under a basal 12 h/12 h light-dark (L-D) cycle. In the vast majority of W (D phase) control animals the SCN was devoid of cells displaying Fos-related immunopositivity, while Fos-like immunoreactive (ir) neurones were detected in most S (L phase) control rats. In most infected animals, on the other hand, Fos-ir neurones were detected in the SCN during W, but not during the S period, with a significant difference between control and infected S rats. Thus, these data indicate that the basal c-fos expression in the SCN during the L-D and S-W cycles is considerably altered in experimental trypanosomiasis. This is the first observation of a selective change in the SCN in trypanosome-infected rat brains. Since the SCN plays an important role as a pace-maker for biological rhythms, this finding may provide a basis for understanding the pathogenesis behind endogenous rhythm dyregulation and changes in sleeping pattern in human trypanosomiasis (African sleeping sickness). PMID- 8199345 TI - Morphine, clonidine coadministration in subanalgesic doses: effective control of tonic pain. AB - The aim of the present study was to investigate whether clonidine and morphine interact positively to produce analgesia against the low intensity tonic pain represented by the formalin model in rats. Sub-threshold doses of morphine (0.5 mg kg-1) and clonidine (0.025 mg kg-1) were found to elicit marked antinociceptive effects when co-administered intraperitoneally, 15 min prior to formalin challenge. Repeated administration of this combination for eight days did not exhibit any significant decay of this analgesic response, whilst morphine (2 mg kg-1)-induced analgesia, deteriorated after similar administration. Clonidine and morphine thus exhibit a supra-additive effect against low intensity pain with negligible potential for induction of tolerance. This finding may be relevant for the long term control of chronic pain in certain clinical conditions. PMID- 8199346 TI - The CCK-B antagonist CI988 enhances the reflex-depressive effect of morphine in axotomized rats. AB - We have examined and compared the effect of systemic CI988, an antagonist of the cholecystokinin B receptor, and morphine on the flexor reflex in rats with intact sciatic nerves and after unilateral axotomy. Intravenous injection of 1 mg kg-1 morphine caused a moderate depression of the flexor reflex in normal and axotomized rats. The duration of morphine-induced depression was significantly shortened in axotomized animals. In contrast, the brief depressive effect of intravenous CI988 on the flexor reflex was significantly enhanced in axotomized rats. Combination of morphine and CI988 resulted in a significant potentiation of reflex depression in rats with intact or sectioned sciatic nerves. It is concluded that blockade of CCK-B receptor potentiated morphine-induced antinociception in rats after peripheral nerve injury. PMID- 8199347 TI - A genetic analysis of neocortical ectopias in New Zealand black autoimmune mice. AB - Two experiments investigated the heritability of neocortical ectopias seen in 30 40% of New Zealand Black (NZB/BINJ) autoimmune mice. The first study examined the brains of mice from the NZB x SM/J recombinant inbred (RI) strains. Fifteen RI inbred strains were examined and over half had ectopias suggesting that a major gene was involved in ectopia production. A follow-up experiment comparing the incidence of ectopias among crosses between NZB and control DBA/2 strains showed that the predisposition to develop ectopias in NZB is a recessively inherited trait with incomplete penetrance. PMID- 8199348 TI - Pressure increases de novo synthesized striatal dopamine release in free-moving rats. AB - When human divers or experimental animals are exposed to high pressure, they develop brain and biobehavioural disorders. Since it has been demonstrated that pressure exposure increased striatal DA release, the present experiments were intended to investigate whether it resulted from a release in de novo synthesized DA or from a release of DA stores. Free-moving rats implanted with multi-fibre carbon electrodes sensitive to DA were pretreated with reserpine, a depleter of catecholamine stores, and compressed to 8 MPa. Results show that pretreatment with reserpine had no ability to block the pressure-induced DA release. In the light of previous relevant studies, we suggested that the elevation of DA release under high pressure would be the consequence of a release in de novo synthesized DA. PMID- 8199349 TI - Dopamine enhances Ca2+ responses in synaptic terminals of retinal bipolar neurons. AB - The effect of dopamine on depolarization-induced Ca2+ influx was studied using the fluorescent Ca2+ indicator fura-2 in synaptic terminals of bipolar neurons from gold-fish retina. Dopamine reversibly enhanced the rise in intracellular Ca2+ elicited by elevated external potassium. The enhancement was slowly reversible. The effect of dopamine was mimicked by forskolin and CPT-cAMP, a membrane-permeant analog of cAMP. However, 1,9-dideoxyforskolin, a forskolin analog that does not activate adenylyl cyclase, was ineffective. This suggests that dopamine, via cAMP, regulates the rise in presynaptic Ca2+ concentration in response to depolarization, potentially enhancing transmitter release. PMID- 8199351 TI - Bibliographic update: nerve growth factor. PMID- 8199352 TI - Cytokine receptors and signal transduction. AB - Cytokines are important regulators of hemopoiesis which exert their actions by binding to specific, high affinity, cell surface receptors. In the past several years, molecular cloning of these receptors has revealed a new superfamily referred to as the hemopoietic growth factor receptors. Members of this family are defined by a 200 amino acid conserved domain; however, it has become increasingly apparent that another characteristic of these receptors is the shared usage of a common signalling subunit among subgroups in this family. The shared signalling component explains the functional redundancy of many cytokines; however, the mechanism by which these receptors transduce a signal across the membrane is not yet clear. Studies into cytokine action have shown that many of the events that occur in response to ligand stimulation are similar to those observed for the better characterized intrinsic tyrosine kinase receptors. Thus, although the cytokine receptors do not possess intrinsic tyrosine kinase activity, these observations have led to a model of cytokine signal transduction adapted from the signalling mechanisms described for the tyrosine kinase receptors. PMID- 8199350 TI - The human and mouse fibroblast growth factor 6 (FGF6) genes and their products: possible implication in muscle development. AB - FGF6 is structurally very similar to the other members of the FGF gene family, and particularly to the FGF4 gene, which was instrumental in its isolation. Its longest open reading frame encodes a 208 amino acid residues long protein, both in man and in the mouse. It is expressed as a 4.8 kb transcript in skeletal muscle. In developing muscle, expression starts at the myotomal stage and culminates in differentiated fetal muscle masses. In culture, FGF6 protein is mitogenic and has a transforming capacity for fibroblasts. It represses the terminal differentiation of myoblasts. Action of FGF6 could be mediated by the FGFR4 receptor, which binds FGF6 and whose gene is also expressed in developing skeletal muscle. PMID- 8199353 TI - Signal transduction by the PDGF receptors. AB - The three isoforms of PDGF bind with different affinities to two related tyrosine kinase receptors, denoted the PDGF alpha- and beta-receptors. Ligand binding induces receptor dimerization, creating receptor homo- or heterodimers. Dimerization is accompanied by, and might be a prerequisite for, receptor autophosphorylation and kinase activation. Receptor autophosphorylation serves to regulate the kinase activity and to create binding sites on the receptor molecule for downstream signalling components. The activities of the signalling components are ultimately manifested as specific biological responses. All the currently described PDGF receptor-binding components, e.g. phospholipase C-gamma, members of the src family of cytoplasmic tyrosine kinases, the rasGT-Pase activating protein and p85, the regulatory subunit of phosphatidylinositol 3' kinase, contain a conserved src homology 2-domain, through which the association with the receptor takes place. The receptor-binding components appear to either possess an intrinsic enzymatic activity, or they function as adaptors, which may complex with catalytically active components. For most receptor-binding components, there is insufficient understanding of how binding to the receptor affects the catalytic function. Certain of these components become tyrosine-phosphorylated, i.e. they are substrates for the receptor tyrosine kinase. Moreover, the change in subcellular localization, which most of the receptor binding components undergo in conjunction with receptor binding, could play a critical role. The current efforts of many laboratories are aimed at delineating different PDGF receptor signal transduction pathways and what roles the different receptor binding components play in the establishment of these pathways. PMID- 8199354 TI - Serine/threonine kinase receptors. AB - A new family of transmembrane receptors that contain intracellular serine/threonine kinase domains is emerging. Ligands for this class of receptors include members of the transforming growth factor-beta (TGF-beta) superfamily, e.g. TGF-beta s and activins. TGF-beta s exert their effects on target cells via formation of heteromeric serine/threonine kinase complexes (TGF-beta type I and type II receptors). Other components, i.e. TGF-beta type III receptor and endoglin, appear to have more indirect roles, e.g. to present ligands to the signalling receptors. Given the structural similarity between members of the TGF beta superfamily, other ligands in this family may act through structurally and functionally similar serine/threonine kinase receptors. PMID- 8199355 TI - Growth factors in Parkinson's disease. AB - The etiology of Parkinson's disease, one of the most frequent neurodegenerative disorders in human, is unknown. New hopes concerning satisfactory therapies include transplants of autologous adrenal medullary chromaffin tissue, fetal mesencephalic dopaminergic neurons, and local application of growth factors with a neurotrophic capacity. A large body of evidence supports the notion that neurons require trophic support not only during a limited period of ontogenesis, but during their whole lifespan. Relevant molecules promote survival, transmitter synthesis and other differentiated properties, and become crucially important when a neuron is metabolically or toxically impaired. Several molecules, most of which occur in the striatum and the substantia nigra, have been identified that protect lesioned dopaminergic nigrostriatal neurons in culture or in animal models of Parkinson's disease. These include members of the neurotrophin, fibroblast growth factor, and insulin-like growth factor families as well as epidermal growth factor/transforming growth factor alpha, interleukins and ciliary neurotrophic factor. Whether their effects are merely pharmacological, or reflect a physiological role in the nigrostriatal system, is unclear as yet. This article reviews experiments that document the trophic effects of these factors on dopaminergic neurons and discusses their possible physiological and therapeutic relevance. PMID- 8199356 TI - Evolution of the transforming growth factor-beta superfamily. AB - Transforming growth factor beta 1 (TGF-beta 1) is the prototype of an increasingly complex superfamily of growth and differentiation factors. To date, a total of 74 TGF-beta-like sequences have been published, probably representing 23 distinct genes. These sequences were obtained from mammalian, avian, amphibian and insect species, thus emphasising the ancient nature of the TGF-beta superfamily peptides. This article summarises current hypotheses concerning the evolutionary history of this protein superfamily, based on the molecular phylogeny of the published sequences. Comparison of the deduced amino acid sequences leads to the definition of five main groups within the superfamily (TGF beta, Bone Morphogenetic Proteins [BMP], Anti-Mullerian Hormone [AMH], Inhibin alpha [INH alpha] and GDF-9) and six subgroups within the BMPs (60A, Decapentaplegic [dpp], Vg1, BMP-3, Inhibin beta [INH beta A/B] and nodal). This classification predicts possible phylogenetic and functional relationships among these proteins. PMID- 8199357 TI - Gas chromatography/combustion/isotope-ratio mass spectrometry analysis of urinary steroids to detect misuse of testosterone in sport. AB - We propose a new confirmatory method for testosterone doping in sport. The present method in use, based on measuring the testosterone/epitestosterone (T/E) ratio in urine, may miss suspicious cases, or lead to reporting cases in which the high ratio is natural. Synthetic testosterone has a 13C abundance different from that of endogenous human testosterone. The connection of a gas chromatograph to an isotope-ratio mass spectrometer via a combustion interface allows the measurement of the corresponding characteristic value (delta /1000) for testosterone, its precursors, and its metabolites. To detect exogenous administration of testosterone, 30-40 mL of urine is sufficient. PMID- 8199358 TI - Analysis of neuropeptides by perfusion liquid chromatography/electrospray ion trap mass spectrometry. AB - Perfusion high-performance liquid chromatography (HPLC) combined with electrospray ion trap mass spectrometry (ITMS) was evaluated for the determination of neuropeptides in plasma. Perfusion HPLC offers the capability of resolving neuropeptides spiked into plasma in 5 min compared to the 30-60 min separations performed on packed capillary C18 columns. Electrospray combined with the ITMS provides the ability to ionize these neuropeptides and mass analyze them with high sensitivity and specificity. Sub-picomole quantities of neuropeptides injected on-column could be specifically detected in a plasma matrix. The electrospray-ITMS mass spectrum of each neuropeptide showed multiply charged ions which could be used to determine or confirm their molecular weights. PMID- 8199359 TI - Arrhythmias. PMID- 8199360 TI - Pediatrics. PMID- 8199361 TI - Congenital heart disease and cardiac surgery in children. AB - In the period reviewed, more than 150 papers were published on congenital heart disease in English, Dutch, Spanish, French, Italian, and German, the majority dealing with specific operative procedures, general surgical management, indications for and results of palliative and corrective operations, and mid- and long-term postoperative outcome. New aspects of cardiological interventions are noteworthy, especially the dilation of valves and vessels and the use of occluding devices in hitherto untouched regions. A great deal of new information has been published with respect to specific lesions, such as tetralogy of Fallot, transposition of the great arteries, pulmonary atresia, and the univentricular circulation. This will certainly change our management of these patients in the future. Several large centers again showed how fruitful the close collaboration between cardiac surgeons and "interventionists" can be. PMID- 8199362 TI - Pediatric arrhythmias. AB - As children with cardiac malformations grow older, it appears that although their hemodynamic abnormalities may have been corrected by surgery, an increasing number of these patients have severe and possibly lethal arrhythmias. Atrial surgery and Fontan-type operations are complicated by atrial tachyarrhythmias that are difficult to predict and control. The relation between sudden death and ventricular tachycardias in patients who have undergone tetralogy of Fallot repair is still controversial. Application of radiofrequency energy now offers an alternative to pharmacologic therapy and surgery for children who have symptomatic tachyarrhythmias and need life-long therapy. Initial results are encouraging, with a very low morbidity, especially for children who have supraventricular reentrant tachycardias due to accessory pathways. However, the place of ablation in children is not yet fully delineated, as long-term follow-up evaluations are still lacking at this time. For this reason, antiarrhythmic agents, including class Ic drugs and amiodarone, should be tried first, especially in very young children. Indications for antiarrhythmic surgery are becoming very rare, due to the introduction of ablation techniques. For children who have life-threatening ventricular arrhythmias, implantation of a cardioverter defibrillator represents a new therapeutic option, one that may also be used as a bridge to heart transplantation. PMID- 8199363 TI - Class III antiarrhythmic drugs. AB - Pharmacological therapy of cardiac arrhythmias continues to evolve, with an increasing shift from class I to class III compounds and beta-blockers. This is engendered by increasing concern that class I antiarrhythmic drugs might adversely affect mortality in patients with significant structural heart disease. The focus now is on complex molecules such as amiodarone and sotalol, as well as D-sotalol and structurally diverse newer class III agents (such as dofetilide, MK 499, ibutilide, almokalant, and MS-551 among many others), which act only by increasing the time course of myocardial repolarization. In the development of newer drugs, the main endpoint in clinical trials is also beginning to shift to mortality from surrogate endpoints such as those determined by Holter monitoring and programmed electrical stimulation. The advent of implantable devices allows the performance of clinical trials with a mortality endpoint in patients with manifest ventricular tachycardia and fibrillation while providing an alternative mode of therapy for these arrhythmias. In the case of manifest ventricular tachycardia and fibrillation and aborted sudden death, adequately designed, controlled trials can now be undertaken by the use of implantable devices. In such trials, implantable cardioverter-defibrillators may serve in lieu of the placebo arm of a randomized trial. Trials involving a comparison of implantable cardioverter-defibrillators and best medical therapy (for the present, amiodarone and sotalol) are currently in progress. To what extent the newer class III agents will meet the requirements of an ideal antifibrillatory agent that reduces mortality in patients with structural heart disease remains a continuing investigative challenge. PMID- 8199364 TI - Acquired heart disease in children. AB - Recent advances have been made in understanding Kawasaki disease, acute rheumatic fever and rheumatic heart disease, cardiomyopathy, and acquired immunodeficiency syndrome. Immune-mediated tissue injury in Kawasaki disease is likely caused by response to a superantigen. Persistent functional and anatomic coronary abnormalities may lead to silent ischemia and increase the risk of early atherosclerotic heart disease. Intravenous immunoglobulin therapy is clearly beneficial, but specific therapy awaits further definition of the etiology and pathophysiology of Kawasaki disease. Recently updated diagnostic criteria for Kawasaki disease and acute rheumatic fever are discussed. Advances in the understanding of genetically determined abnormal immune responses to streptococcal pharyngitis may help explain acute rheumatic fever manifestations. Further advances have been made in the elucidation of the pathophysiology of cardiomyopathy, particularly the role of viruses and genetic factors. Angiotensin converting enzyme inhibitors appear to improve survival in dilated cardiomyopathy. Controversy regarding the possible myocardial depressant effect of zidovudine in human immunodeficiency virus infection is discussed. PMID- 8199365 TI - Hypertension and atherosclerosis in children. AB - This article reviews important advances in the understanding and treatment of hypercholesterolemia and persistently high blood pressure in children. Two plant sterols, sitosterol and sitostanol, have been tested in prepubertal and adolescent children with hypercholesterolemia and appear promising. The advantages and disadvantages of family history in screening algorithms for atherosclerotic disease are discussed. Additionally, the apolipoproteins are being used more frequently to screen for cardiovascular risk. A rare genetic disease, familial defective apolipoprotein B-100, causes hypercholesterolemia. The distinction between this disease and familial hypercholesterolemia has therapeutic implications. Two studies show that in utero exposures influence the future development of hypertension. Intrauterine cocaine exposure was associated with persistently elevated blood pressure during later childhood. The mechanism may involve the sympathetic nervous system. Retarded fetal growth appears to be a risk factor for the presence of hypertension during adult years in men. PMID- 8199366 TI - Adult congenital heart disease. AB - There are approximately 500,000 adults in the United States with congenital heart disease, and this group is growing at 5% per year. Adult cardiologists are, for the most part, poorly trained in the treatment of congenital heart disease; pediatric cardiologists, on the other hand, work in children's hospitals where it is difficult to care for adults. It is important, therefore, to review the current literature as it relates to adult congenital heart disease. This report details the long-term follow-up of patients who were operated on in childhood for congenital heart disease and are now adults. In addition, it reviews information related to the social adaptation of adult congenital heart patients. There are a number of interesting new reports on specific adult congenital heart anomalies. Atrial septal defects as well as the relationship between a patent foramen ovale and stroke are also reviewed. PMID- 8199367 TI - Advances in implantable cardioverter-defibrillator therapy. AB - The use of implantable defibrillation systems in patients with cardiac arrest has resulted in lower mortality than expected from studies of similar patients not receiving defibrillators. Nonthoracotomy lead systems have led to a decrease in operative mortality and lowered the cost of defibrillator implantation, but these systems have a higher energy requirement for defibrillation than do epicardial ones. The recent introduction of single-lead systems and bipolar defibrillation pulses has simplified nonthoracotomy defibrillator implantation and improved defibrillation efficiency. A prototype unipolar, single-lead pectoral implant defibrillation system is described that may significantly improve the reliability, safety, and cost effectiveness of nonthoracotomy defibrillators. This and other improved nonthoracotomy systems may expand the indications for defibrillator implantation to prophylactic use in high-risk patients who have not yet experienced life-threatening ventricular arrhythmias. PMID- 8199368 TI - Recent insights in programmed electrical stimulation for the management of sustained ventricular arrhythmias. AB - After more than 20 years of clinical use, programmed electrical stimulation for induction of cardiac arrhythmias remains an important clinical and research tool. The procedure continues to undergo refinement but is not without controversy regarding its accuracy in predicting drug efficacy as determined by serial testing for suppression of ventricular tachyarrhythmias. Recent work has streamlined technical aspects of the procedure itself and promises to improve the selection of patients likely to benefit from such studies. Despite these advances, however, recent publications from the Electrophysiologic Study Versus Electrocardiographic Monitoring trial raise fundamental questions about the ability of any current strategy to predict the efficacy of antiarrhythmic drugs for the prevention of ventricular arrhythmias. PMID- 8199369 TI - Current management of atrial fibrillation. AB - A resurgence of interest in atrial fibrillation has led to research in several avenues. Observations on the behavior of the atrium during atrial fibrillation demonstrate that electrical activity is not entirely random and that sinus node activity persists despite surrounding fibrillation. Anticoagulation therapy for chronic atrial fibrillation is now accepted as optimal treatment, but randomized trials have excluded the majority of patients screened and the risk-benefit ratio of therapy in the average patient therefore remains unclear. This is being addressed in comparative trials of warfarin and aspirin and in an analysis of risk factors for stroke derived from a major trial. Assessment of the efficacy of therapy for the control of ventricular rate in atrial fibrillation has underscored the slow action of digoxin and raised the issue of suboptimal dosing. With the recognition that improvement of exercise capacity following cardioversion may be postponed for weeks, several studies have evaluated serial changes in ventricular function and shown that in some patients sinus rhythm is associated with an improved ejection fraction. Transesophageal echocardiography is an area of intense interest for the identification of patients at high risk of thromboembolism following cardioversion, and the significance of left atrial spontaneous echo contrast as well as the left atrial appendage contractile function are being investigated. Finally, new methods of arrhythmia termination are being evaluated and developed, and surgical approaches to atrial fibrillation are being expanded and refined. PMID- 8199370 TI - Role of catheter ablation for supraventricular tachyarrhythmias, with emphasis on atrial flutter and atrial tachycardia. AB - Catheter ablation techniques using radiofrequency current have become an accepted form of treatment for a variety of supraventricular tachycardias. The results are excellent in patients with preexcitation syndromes and as the complication rate is low, catheter ablation has become the first line of treatment for these disorders. In atrioventricular nodal reentry, a selective ablation of the fast or slow pathway is feasible. Ablation of the slow pathway guided by electrophysiologic markers appears to be safer with the use of a very low number of radiofrequency applications. Experience with atrial tachycardia remains limited but developments appear promising. Lastly, atrial flutter has become a growing indication for catheter ablation techniques using anatomical approaches. A high success rate can be achieved initially, but the technique is limited by a 20% recurrence rate and the late occurrence of atrial fibrillation. PMID- 8199371 TI - Neurally mediated syncope with an update on indications and usefulness of head upright tilt table testing and pharmacologic therapy. AB - Neurally mediated episodes of hypotension and bradycardia (neurocardiogenic syncope) are a common cause of recurrent syncope. Clinically, these episodes may present as an isolated event with an identifiable stimulus, or manifest as a syndrome of recurrent idiopathic syncopal events. The technique of head-upright tilt table testing has emerged as a safe and effective modality to identify individuals with this disorder. The use of isoproterenol as an adjunct to tilt table testing is widely employed although controversial. Whereas the mechanism of neurally mediated syncope is incompletely understood, effective therapies are available. Multiple pharmacologic agents, either alone or in combination, have proven effective in preventing recurrent episodes. The role of cardiac pacing as therapy for a subgroup of patients who manifest severe bradycardia or asystole remains controversial as well. Additional study is necessary to further define the mechanism of neurally mediated syncope, provide new therapeutic strategies, and perhaps provide alternative diagnostic techniques. PMID- 8199372 TI - Recent advances in cardiac pacing. AB - This article reviews recent studies, chapters, and review articles describing advances in cardiac pacing. Initially we discuss expanding and controversial pacing indications, including neurocardiogenic syncope and hypertrophic as well as dilated cardiomyopathies. Recent contributions to the understanding of factors influencing pacing mode selection are then discussed, including survival and atrial fibrillation in the various modes, the hemodynamic importance of atrioventricular synchrony and adaptive atrioventricular intervals, the importance of rate adaptation, the development of pacemaker syndrome, pacemaker response to the development of atrial arrhythmias, and special pacing modes such as VDD and AAIR. Finally, recent advances in rate-adaptive sensors and algorithms are reviewed, including preliminary results with dual sensors. PMID- 8199373 TI - Pediatric cardiology and US health care. PMID- 8199374 TI - The subcellular basis for the perinatal maturation of the cardiocyte. AB - In the experimental animal, the transition from tetus to newborn to adult has long been associated with an improvement in systolic and diastolic cardiac function. Recent studies using noninvasive methods have demonstrated a similar perinatal improvement in ventricular function in the human. These perinatal changes in cardiac function have been correlated with subcellular changes in expression of sarcoplasmic reticulum Ca2+ release channel and Ca2+ ATPase proteins (the primary regulators of phasic Ca2+ cycling in the mature heart), as well as with isoform switching among the myofibrillar proteins. The reduced sarcoplasmic reticulum-dependent regulation strongly supports the concept that during perinatal maturation, systolic and diastolic cardiac function are more dependent on transsarcolemmal Ca2+ flux. PMID- 8199375 TI - Fetal arrhythmias. AB - The increased awareness of fetal arrhythmias by obstetricians and the development of sophisticated fetal echocardiography have established the basis for identification and treatment of these arrhythmias. The development of fetal hydrops is a recognized link to the severity of the arrhythmia. Fetal tachycardias have been diagnosed relatively early in gestation. They may be differentiated into sinus tachycardia, supraventricular tachycardia, atrial flutter or fibrillation, and ventricular tachycardia. The need for prenatal treatment is widely accepted and various modes of therapy are advocated. Oral maternal antiarrhythmic medication is often used, is considered convenient and safe, and provides adequate conversion. The drugs of choice at various centers have included digoxin, flecainide, amiodarone, and a host of combinations, as well as sotalol, which is gaining popularity. At birth, reentry mechanisms are often documented, with frequent relapses of tachycardia, warranting postpartum continuation of treatment. Fetal bradycardias consist of sinus bradycardia (generally related to obstetric pathology) and atrioventricular block. Atrioventricular block may occur secondary to severe congenital heart disease in the fetus or as an isolated phenomenon. The development of isolated total atrioventricular block has been seen to occur from a gestational age of 18 weeks up to term. It is invariably accompanied by the presence of SS-A and SS-B autoantibodies in the mother. Passage of these antibodies across the placenta causes inflammatory disease of fetal atrioventricular node tissue, resulting in fibrosis and atrioventricular block.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199376 TI - Valvular heart disease. PMID- 8199377 TI - Surgery. PMID- 8199378 TI - Valvular heart disease. PMID- 8199379 TI - Mitral valve disease. AB - Recent experimental work demonstrates that the cellular contractile dysfunction that occurs after a brief period of mitral regurgitation is potentially reversible, that left ventricular dysfunction may also occur due to interruption of chordal-ventricular continuity, and that muscle dysfunction can be detected independent of loading conditions with measurements of ventricular stress and strain. Experimental work has also shown that hypertrophy after experimental mitral regurgitation may be inadequate for the degree of hemodynamic overload, and that there is lysis of myofibrils. This is consistent with clinical observations that ventricular dilatation and left ventricular hypertrophy may be modest despite long-standing, severe mitral regurgitation. At the moment, end systolic diameter remains the best predictor of outcome after mitral valve replacement; preservation of chordae has been shown to have an impact on outcome in some but not all studies. Measures of heart rate variability may also have predictive value in mitral regurgitation. The so-called myocardial factor in rheumatic mitral disease appears to be unimportant; excessive vasoconstriction is more responsible for the modest left ventricular dysfunction in mitral stenosis. There is some new information regarding beta-blocking therapy, vasodilator therapy, and antithrombotic therapy. PMID- 8199380 TI - Aortic valve disease. AB - Management of aortic valve disease follows traditional algorithms: initial gross diagnosis, noninvasive imaging and quantitation, possible catheterization or angiography, and medical treatment until symptoms of prognosis prediction indicates surgery. Most advances in this subject reflect improved technology and additional data collection therefrom, and subsequent analysis. Noninvasive imaging, especially Doppler echocardiography and nuclear magnetic resonance imaging, enjoy continued refinement. Diastolic dysfunction, a particular pathophysiologic feature of aortic valve disease, has become more clearly characterized. New data reaffirm the old truth that heart failure in infective endocarditis foretells the need for surgery. Though we know more about aortic balloon valvotomy, it is only a temporary treatment. Surgeons still seek the perfect valve prosthesis. Lastly, technology has not lessened the high incidence of rheumatic heart disease in impoverished countries. PMID- 8199381 TI - Echocardiography in valvular heart disease. AB - Transthoracic Doppler echocardiography continues to play a predominant role in the evaluation of patients with valvular heart disease. Current efforts in the research arena have been focused on improving the accuracy of techniques, as well as in further describing the shortcomings. Accurate quantitation of valvular regurgitation continues to be a major stumbling block. However, more sophisticated techniques are being successfully applied to obviate some of the limitations of color flow imaging. Transesophageal echocardiography has provided a new window and clarity of resolution that greatly facilitates evaluation of valvular heart disease in cases where the transthoracic approach is limited, particularly in patients with prosthetic valves. PMID- 8199382 TI - Percutaneous mitral balloon valvotomy for patients with mitral stenosis. AB - This study reports the immediate outcome, in-hospital complications, and long term clinical follow-up of patients undergoing percutaneous mitral balloon valvotomy. In most series, this procedure is reported to increase mitral valve area from less than 1.0 cm2 to at least 2.0 cm2. The most important predictor of the immediate outcome of percutaneous mitral valvotomy is the echocardiographic score. The best results with percutaneous mitral valvotomy occur in those patients with echocardiographic scores of 8 or less. Mortality and morbidity with percutaneous mitral valvotomy are low and similar to surgical commissurotomy. There is less than 1% mortality, a 0% to 3.1% incidence of thromboembolic episodes and stroke, a 1% to 5.2% incidence of severe mitral regurgitation, a 0.2% to 4.1% incidence of pericardial tamponade, and a 3% to 16% incidence of left-to-right shunt. Survival (83 +/- 6% vs 48 +/- 8%), survival with freedom from mitral valve surgery (58 +/- 5% vs 25 +/- 5%), and event-free survival (51 +/- 6% vs 22 +/- 5%) at 80-month follow-up was greater in patients with echocardiographic scores of 8 or less compared with those with scores greater than 8 (P < 0.0001). Thus, the excellent immediate and long term results of percutaneous mitral valvotomy in patients with echocardiographic scores of 8 or less suggest that this procedure may be the treatment of choice in this group of patients. PMID- 8199383 TI - Endocarditis. AB - The continuing medical literature attests to the fact that infective endocarditis is a serious and complex disease, which in many populations continues to occur at an incidence of approximately 20 per 100,000, and carries a 5% to 40% mortality, depending on numerous pathogen and patient factors. Clinical investigation continues along several lines, including analysis of the clinical utility of diagnostic imaging, especially the contribution of transthoracic and transesophageal echocardiography (and, conversely, the risk of endocarditis from transesophageal imaging). Epidemiological and cohort descriptive studies give insight into the underlying causes of the disease, and risk factors for poor outcome, from which guidelines for management can be surmised. PMID- 8199384 TI - Right-sided valvular pathology and rheumatic fever. AB - This paper discusses some of the recent advances in the evaluation and treatment of right-sided cardiac pathology, and reviews the more general subject of rheumatic fever, with particular emphasis on diagnosis and possible genetic influences. A comprehensive assessment of these topics is not intended; rather, interesting features and recently published long-term outcome data of more common right heart abnormalities are summarized. PMID- 8199385 TI - Current status of valvular surgery. AB - Surgical treatment of valvular heart disease is a field of constant clinical and experimental research. Recently, much attention has been devoted to the improvement of valve repair techniques. The physiopathology of the left ventricular outflow tract obstruction following mitral valve repair has become better understood. Surgical techniques to correct this infrequent complication have been developed. Conservative valvular surgery or homograft use are among the surgical treatments for infective endocarditis; innovative experimental and clinical studies on mitral and tricuspid homografts have provided interesting results. New biological valves have come into use; intraoperative creation of a cardiac bioprosthesis using glutaraldehyde-treated autologous pericardium is an attractive surgical innovation. Stentless bioprostheses are also under investigation, to evaluate their hemodynamic and clinical characteristics. The biology of bioprosthesis deterioration progresses at the cellular level, with the implication of phagocytosis as a contributing factor. PMID- 8199386 TI - Aortic dissection and aortic aneurysm surgery. AB - During the last year, the role of noninvasive studies for aortic dissection- magnetic resonance imaging, computed tomography scanning, and transesophageal echocardiography--has become better defined. Both magnetic resonance imaging and transesophageal echocardiography are highly accurate in detecting aortic dissection. On transesophageal echocardiographic imaging of the ascending aorta, artifacts may be present that mimic an intimal flap (septum). These linear echo densities have characteristic features which distinguish them from a true intimal flap (septum). Their recognition is critical in avoiding false positive transesophageal echocardiography findings. The general consensus on operations for ascending aorta and aortic arch dissection is that patients should be operated upon immediately. Controversy still remains, however, as to whether the aortic arch needs replacement at the time of the ascending and proximal aortic arch repair. Most authors agree that deep hypothermia with circulatory arrest is the preferable technique for acute aortic dissection repair and for surgery on the aortic arch in adults. Retrograde perfusion of the jugular veins is an added advantage. For acute aortic dissection involving the descending thoracic or thoracoabdominal aorta, evidence continues to accumulate that initial medical therapy with beta-blockers and antihypertensives is the preferable mode of treatment unless complications requiring surgery arise. Percutaneous techniques are increasingly being described, including fenestration of the aortic dissection septum, stenting of the aorta or aortic branches, and insertion of intraluminal aortic tube grafts. The safety of surgery on the thoracoabdominal aorta and on the descending thoracic aorta, including the prevention of complications, is reviewed. PMID- 8199387 TI - Surgery for congenital heart disease. AB - Natural and postintervention studies have updated the expected outcomes for patients with pulmonary atresia with an intact ventricular septum, critical pulmonary stenosis, transposition of the great arteries, tricuspid atresia, and for recipients of pediatric transplants. Innovative surgical and nonsurgical procedures have been proposed for patients with systemic right ventricular failure, atrioventricular discordance, and coarctation of the aorta. This review highlights these and other important topics from this year's literature. PMID- 8199388 TI - Surgery for ischemic heart disease. AB - Surgical treatment for ischemic heart disease continues to evolve. The long-term benefit of coronary artery bypass grafting can be shown to extend for 15 to 20 years. The long-term patency achieved with internal thoracic artery grafts has extended the already good results of coronary artery bypass grafting. It is the surgeon's hope that the pursuit of multiple arterial grafting will further extend these results. Operations continue to increase in complexity and include a growing number of reoperations. Techniques to deal with these situations have continued to evolve so that the operative mortality remains low. The role of angioplasty in patients with multiple-vessel coronary artery disease has not been firmly established. However, increasing data indicate that in patients with triple-vessel disease and depressed ventricular function, complete surgical revascularization is the treatment of choice. PMID- 8199389 TI - Surgery for cardiac arrhythmias. AB - The field of arrhythmia surgery has changed markedly over the past several years. The increased effectiveness of catheter ablation for the treatment of supraventricular tachycardias, the increasingly common use of surgical techniques for treating atrial fibrillation, and the continued refinement of implantable cardioverter-defibrillator technology have all altered decision-making regarding the treatment of patients with medically refractory symptomatic arrhythmias. The effects that these changes have had on patient selection and therapeutic outcomes resulted in the publication of a number of articles concerning arrhythmia surgery during the past year. Several of the most important changes in the treatment of patients with supraventricular and ventricular arrhythmias are reviewed. PMID- 8199390 TI - Mechanical circulatory support of the failing heart. AB - Over the past 30 years, there have been significant pharmacological and technological advances in the treatment of cardiogenic shock. Although most patients who develop cardiogenic shock can be effectively treated with conventional therapy, including inotropic and vasodilating drugs and intra-aortic balloon pumps, a significant number of patients have ventricular failure that is refractory to conventional therapy. For these patients, the prognosis is poor unless the deleterious effects of cardiogenic shock can be reversed. For some, cardiac revascularization or the repair of mechanical defects reverses the hemodynamic deterioration. However, there are subgroups of patients in whom an advanced form of mechanical circulatory support is necessary for myocardial recovery or in whom recovery will never occur, but who may be candidates for cardiac transplantation. PMID- 8199391 TI - Developments in cardiac transplantation. AB - Cardiac transplantation has matured as a therapeutic intervention, allowing definitive treatment of critically ill children and adults with end-stage heart disease. The ongoing critical shortage of donor organs continues to deny hundreds of individuals access to this intervention. Accordingly, many of the most meaningful recent advances made in the field of cardiac transplantation involve means of expanding our donor pool. While current immunosuppressive regimens have been considerably successful in the management of acute cellular rejection, management of the problems of acute and chronic vascular rejection remains disappointing. Advances in this arena remain particularly urgent for physicians and surgeons involved in the care of heart transplant recipients. PMID- 8199392 TI - Perfusion and cardioplegia. AB - The focus of the reports reviewed in the last year has shifted to "outcomes," perhaps in response to the pressures of national health care reform. With regards to the extracorporeal circulation requisite for complex cardiac repair, emphasis is placed on anticoagulation management, blood use and its systemic effects, cognitive outcome after cardiac operations, and the requirement and effects of intra-aortic balloon pumping on weaning from bypass. Additionally, interest in the systemic effects of prolonged warm perfusion consequent to the novel myocardial management strategy of warm cardioplegia is evident. Advances in cardioplegia have shifted predominantly toward additives, with specific emphasis on modulating inflammation, enhancing the metabolic substrate, and limiting toxic oxygen free radical injury and the ischemia-induced accumulation of cations. PMID- 8199393 TI - Optimal management of older patients with atrial fibrillation. AB - Long term oral warfarin should be administered to elderly patients with atrial fibrillation who are at high risk for developing thromboembolic stroke and who have no contraindications to anticoagulant therapy. Oral aspirin (acetylsalicylic acid) 325mg daily may be given to elderly patients with chronic atrial fibrillation who have contraindications to anticoagulant therapy or who are not at high risk for developing thromboembolic stroke. Management of atrial fibrillation includes treatment of the underlying disease and precipitating factors. If patients have paroxysmal atrial fibrillation with a very rapid ventricular rate associated with hypotension, severe left ventricular failure or chest pain due to myocardial ischaemia, immediate direct-current cardioversion should be performed. Intravenous verapamil, diltiazem or a beta-blocker should be used for immediate slowing of a very rapid ventricular rate associated with atrial fibrillation. If a rapid ventricular rate associated with atrial fibrillation persists at rest or during exercise despite digoxin, then oral verapamil, diltiazem or a beta-blocker should be added. Low dosages of oral amiodarone (200 to 400 mg/day) may be used in selected patients with symptomatic life-threatening atrial fibrillation refractory to other therapy. No medication which depresses atrioventricular conduction should be given to patients with atrial fibrillation and a slow ventricular rate. Cardioversion should not be performed in asymptomatic elderly patients with chronic atrial fibrillation. This author would use a beta-blocker for control of ventricular arrhythmias and following conversion of atrial fibrillation to sinus rhythm. Should atrial fibrillation recur, beta-blockers have the additional advantage of slowing the ventricular rate. PMID- 8199394 TI - Skin growths in the aged. Treatment considerations. AB - Skin disorders are very common among elderly people. All physicians who care for this population should possess the ability to recognise common benign growths. Primary care physicians should also have the ability to recognise premalignant and malignant lesions, so that early diagnosis and treatment is possible. It is puzzling that the organ system most amenable to examination is so often overlooked in routine examinations. By simply taking the time to perform a skin examination, morbidity and mortality can be decreased. Through improvements in pharmacotherapy, particularly the development of more effective sunscreens, it may eventually be possible to markedly reduce the development of many benign and malignant skin lesions. PMID- 8199395 TI - Physiological changes due to age. Implications for respiratory drug therapy. AB - The pulmonary system is modified in various ways over time and it is particularly vulnerable to environmental insults. Of particular interest are the implications of aging for therapy of respiratory illnesses. The changes in pulmonary structure and function due simply to aging, and changes due to diseases, should be distinguished from each other. The great reserve function of the lung permits reasonable physical capacity in healthy individuals despite aging changes. In principle, loss of function equivalent to more than one lung is necessary to impair aerobic capacity at any age. Elderly people are subject to the same respiratory diseases as younger adults but may manifest them differently. They may present in atypical ways such as in bacterial pneumonia, tuberculosis, and asthma, all modified by anatomical alterations or deterioration of immunological defence mechanisms. Accumulation of toxic substances over time such as cigarette smoke or environmental pollutants may give rise to chronic bronchitis, emphysema, bronchogenic carcinoma and interstitial lung disease. Changes in the number or function of airway receptors modulate responses to bronchodilator drugs. Chronic inflammation of the bronchial wall has blurred the distinction between traditional asthma and chronic bronchitis and emphysema, and similar drug therapy can be useful for all. Adverse reactions to respiratory drugs such as theophylline, oral corticosteroids, and isoniazid increase with age. As more data accumulate, drug therapy of respiratory diseases in older patients will become more effective and safer. PMID- 8199397 TI - Transdermal estradiol/norethisterone. A review of its pharmacological properties and clinical use in postmenopausal women. AB - The combined transdermal estradiol/norethisterone therapeutic system is designed to deliver both estradiol and norethisterone into the systemic circulation at a constant rate for up to 4 days when affixed to the skin. Transdermal administration avoids hepatic first-pass metabolism, allowing therapeutic concentrations of the progestogen and estrogen to be maintained in postmenopausal women following low dose administration. Transdermal norethisterone does not appear to alter the potentially beneficial effects of transdermal estradiol on total cholesterol, low-density lipoprotein (LDL) or triglyceride levels, or metabolic parameters of bone resorption or vaginal cytology. Protection of the endometrium from the effects of unopposed estradiol is achieved by sequential treatment with transdermal estradiol/norethisterone for 2 weeks of each 28-day cycle, and the majority of patients experience a regular vaginal bleeding pattern with this treatment regimen. Menopausal symptoms are improved to a similar extent during the transdermal estradiol-only and combined estradiol/norethisterone treatment phases. The transdermal therapeutic system has been well accepted by patients in clinical trials. It is generally well tolerated, the most common adverse effect being local irritation at the site of application. Estrogen- and progestogen-related systemic adverse events are reported in a small proportion of patients. Thus, the combined estradiol/norethisterone transdermal delivery system offers a more convenient and consistent method of progestogen administration. Together with its therapeutic efficacy when administered at lower dosages than oral therapy, it is likely to further improve patient compliance during hormone replacement therapy. PMID- 8199399 TI - Technology advancement for studying gene expression and gene function: a workshop report. Sponsored by National Institute of Child Health and Human Development, National Institute of General Medical Sciences, National Center for Human Genome Research, National Center for Research Resources, National Institutes of Health, Bethesda, Maryland 20892, USA. PMID- 8199398 TI - Aniracetam. An overview of its pharmacodynamic and pharmacokinetic properties, and a review of its therapeutic potential in senile cognitive disorders. AB - Aniracetam is a member of the nootropic class of drugs, which have possible cognition enhancing effects. It appears to positively modulate metabotropic glutamate receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-sensitive glutamate receptors, and may facilitate cholinergic transmission, effects which are possibly related to its mechanism of action. Results from trials in elderly patients with mild to moderate cognitive impairment due to senile dementia of the Alzheimer type suggest that aniracetam may be of benefit, with further trials required to confirm its efficacy profile and to define more precisely those patients most likely to respond to treatment. Aniracetam 1500 mg/day was significantly more effective than placebo in all tests at 4 and 6 months, and in a further 6-month trial was more effective than piracetam 2400 mg/day in 8 of 18 tests. Preliminary evidence in the treatment of patients with cognitive impairment of cerebrovascular origin suggests aniracetam may also be of benefit in this condition. Whilst incidence rates of adverse effects are not yet available, data from trials suggest aniracetam is well tolerated. In particular, aniracetam does not appear to cause increases in liver enzyme levels. The evaluation of drugs for patients with senile cognitive disorders is a difficult area and therapeutic options are currently limited. Preliminary evidence of the potential benefits and good tolerability profile of aniracetam support continued evaluation of its use in patients with mild to moderate senile dementia of the Alzheimer type. PMID- 8199396 TI - Endothelins. A potential target for pharmacological intervention in diseases of the elderly. AB - The existence of vasoconstrictive factors originating from the endothelium was confirmed by the description of endothelin, a 21-amino-acid peptide derived from a series of precursors, preproendothelin and a 38-amino-acid big endothelin. Three isoforms of endothelin, endothelin-1, -2 and -3, and 3 receptors (ETA, ETB and ETC) have been described and cloned. The cellular mode of action of endothelin seems to involve the modulation of intracellular calcium (through inositol trisphosphate, diacylglycerol and phospholipase C) and activation of calcium channels. The effects of endothelin are predominantly on the cardiovascular system. Its major effect is vasoconstriction, both systemic and pulmonary, with additional positive chronotropic and inotropic effects on the heart. It has also been implicated in homeostatic regulation of kidney microcirculation, and has powerful mitogenic effects on fibroblasts and smooth muscle cells. Many additional effects have been described on the endocrine system and on other systems. However, the clinical relevance of such effects is uncertain. Increased plasma endothelin levels have been reported in many diseases, but as yet it is not certain whether they are a cause or a consequence of the pathology. Pathologies most probably related to endothelin dysfunction are the vasospastic diseases, especially vasospasm after subarachnoid haemorrhage. Endothelin could be implicated to a lesser measure in diseases typical of the elderly population, such as hypertension or atherosclerosis. Drugs are being developed which act on endothelin metabolism, the most promising of which appear to be the inhibitors of endothelin converting enzyme and endothelin receptor antagonists. Some already existing drugs, such as calcium channel blockers or angiotensin converting enzyme inhibitors, probably act at least in part by interfering with endothelin metabolism or effects. PMID- 8199400 TI - Identification of tissue-specific expressed sequences in human band Xq28 with complex pig cDNA probes. AB - As a part of the functional analysis of the region from the position of the fragile X mutation to the telomere of the long arm of the human X Chromosome (Chr), we have developed a number of different approaches to identify genes located in this area. We describe here a procedure allowing the rapid identification of expressed sequences based on the hybridization of radioactively labeled complex cDNA probes derived from different pig and human tissues to cosmid clones gridded onto nylon filters and to restriction fragments of these clones. This technique has allowed the identification of a number of differentially expressed sequences in cosmid clones covering most of the Xq27.3 to Xqter region. Using these sequences as hybridization probes, cDNA clones for new genes expressed in a tissue-specific manner were isolated. Applied to genomic regions defined by overlapping cosmid clones, this method will serve as a major component in our strategy to establish integrated physical and transcription maps. PMID- 8199401 TI - Gene mapping from a bovine 1;29 DNA library prepared with chromosome microdissection. AB - Bovine gene mapping is progressing rapidly using syntenic group mapping based on somatic cell hybrids and linkage, and to a lesser extent on in situ hybridization. Single chromosome DNA libraries are a logical next step, and this was, therefore, the aim of our laboratory. Since we have access to several cattle with t(1;29) and this chromosome is readily distinguishable, we chose this as our first target--recognizing that we would not produce a "single" chromosome library in the strict sense because two autosomes are represented. We utilized an inverted microscope and a micromanipulator fitted with glass instruments pulled specifically to dissect off approximately 100 t(1;29) chromosomes per microdrop. A glass chamber made to accommodate a hanging drop was used to extract the DNA under a dissecting microscope. The DNA was then cleaved with EcoRI and inserted in lambda gtwes arms. Host cells were then infected with these phage and positive clones obtained. The first clone, isolated from this library by hybridization with a human collagen 6A1 cDNA, was mapped by in situ hybridization to bovine Chromosome some (Chr) 1q12-q14, near the centromere. The second clone, an anonymous DNA fragment (D1S11), was mapped to 1q43-q46, near the terminal end. PMID- 8199402 TI - Disappearance of polycystic kidney disease in revertant c-myc transgenic mice. AB - Nineteen SBM transgenic mouse lines specifically expressing the c-myc protooncogene in renal epithelium Transgene expression is completely penetrant, leading to death from renal failure. In the course of continuous breeding of eight transgenic lines, all lines underwent spontaneous transgene mutations characterized by partial deletion and probable rearrangement of the transgene insert. Revertant mice and their progeny have no evidence of renal disease. This constitutes the first report of spontaneous mutations occurring within transgene inserts. The high spontaneous mutation frequency of 10(-2) to 10(-3) greatly exceeds that of naturally occurring mutations and is probably favored by the transgene's multiple tandem insertion. These spontaneous mutations demonstrate that the intact transgene is necessary and sufficient to produce the SBM phenotype. Further, these results implicate deregulation of factor(s) governing epithelial cell proliferation in the pathogenesis of PKD in SBM mice. PMID- 8199403 TI - Chromosomal assignment of four genes encoding Na/H exchanger isoforms in human and rat. AB - The plasma membrane Na/H exchanger plays an essential role in regulating intracellular pH and Na+ concentration and has been implicated in several pathophysiological conditions, including essential hypertension and congenital secretory diarrhea. Four isoforms of the Na/H exchanger encoded by separate genes have recently been identified by cDNA cloning. To map their locations in the human and rat genomes, rat isoform-specific cDNA probes were hybridized to Southern filters containing panels of somatic cell hybrids that segregate either human or rat chromosomes. The rat Nhe1 gene was assigned to Chromosome (Chr)5, extending the homology with human chromosome 1p that has previously been shown to contain the human NHE1 gene. The genes encoding the NHE-2 and NHE-4 isoforms were syntenic in the two species and assigned to rat Chr 9 and human Chr 2. A single Nhe3 gene was detected in rat and assigned to Chr 1. In contrast, although evidence to date has suggested a single human NHE3 gene on Chr 5, two NHE3 genes, NHE3A and NHE3B, were identified and assigned to Chrs 10 and 5, respectively. Interestingly, rat Chr 1 has recently been found to carry a gene controlling systolic blood pressure upon sodium loading in stroke-prone, spontaneously hypertensive rats. Thus, this and other evidence implicates rat Nhe3 as a possible candidate gene in this disease process. PMID- 8199404 TI - In situ hybridization mapping of the growth hormone receptor (GHR) gene assigns a linkage group (C9, FS, GHR, and S0105) to chromosome 16 in pigs. PMID- 8199405 TI - Exclusion of two candidate genes, Spnb-2 and Dcd, for the wobbler spinal muscular atrophy gene on proximal mouse chromosome 11. PMID- 8199406 TI - Mapping of an insulin-dependent diabetes locus, Idd9, in NOD mice to chromosome 4. PMID- 8199407 TI - Distribution of two conserved, male-enriched repeat families on the Bos taurus Y chromosome. PMID- 8199408 TI - New microsatellite size variants as markers for a cross-over hotspot in the C4-H 2D region. PMID- 8199409 TI - A rapid method to isolate microsatellite markers from cosmid clones. PMID- 8199411 TI - A rapid method of scoring simple sequence repeat polymorphisms with agarose gel electrophoresis. PMID- 8199410 TI - Neomycin- and hygromycin-resistance expression cassettes containing an artificial triple-helix site and a synthetic lac operator facilitate restriction endonuclease cleavage at pre-defined sites and recovery of specific fragments from mammalian genomes. PMID- 8199412 TI - Strain distribution patterns for 50 SSLP markers in the murine AKXL recombinant inbred set. PMID- 8199413 TI - The gene for mouse p58cdc2L1 (Cdc2l1) protein kinase maps to distal mouse chromosome 4. PMID- 8199414 TI - Mapping the peroxisome proliferator-activated receptor to chromosome 15 in the mouse. PMID- 8199415 TI - Nutritional support dietetics: past, present, and future. PMID- 8199416 TI - Taurine-supplemented total parenteral nutrition and taurine status of malnourished cancer patients. AB - The status of plasma taurine and whether its concentration can be influenced by total parenteral nutrition (TPN) was determined in 51 malnourished fasting cancer patients after surgery and 7-14 days after starting TPN providing 41 +/- 2 kcal, 0.30 +/- 0.02 g N kg-1.day-1 and 40 mg pyridoxine. Plasma taurine was 50% lower in patients than in control subjects. Plasma taurine was significantly greater than baseline only after 14 days of TPN. We also studied the effects of surgery and taurine supplementation (8.6 mg.kg-1.day-1) on plasma and urine taurine concentrations in 12 malnourished patients. Preoperatively, all patients had normal plasma taurine concentrations; postoperatively, it was in the deficient range in 4 patients. Taurine-supplemented patients initially had higher than baseline concentrations; by day 10, none had subnormal levels. Subnormal taurine concentrations commonly occur in malnourished postoperative cancer patients; surgery further precipitates their fall. Plasma concentrations were maintained only with taurine-supplemented TPN. PMID- 8199417 TI - Inadequate dietary intake and altered nutrition status in early HIV-1 infection. AB - Recent studies indicate that multiple nutritional abnormalities occur relatively early in the course of human immunodeficiency virus (HIV-1) infection. Decreased plasma levels of vitamins B6, B12, A, and E and zinc have been correlated with dietary intake and associated with significant alterations in immune response and cognitive function. To determine the level of intake consistent with normal plasma nutrient levels, we examined nutrition status in relation to food consumption and nutrient supplementation in HIV-1-seropositive (HIV+) and seronegative (HIV-) homosexual men. The mean level of total intake (diet plus supplements) for all nutrients was significantly higher in HIV+ men. To achieve normal plasma nutrient values, the HIV+ men appeared to require intake in multiples of the recommended dietary allowance (RDA) for vitamins A, E, B6, and B12 and zinc. For the HIV+ men, a relatively high proportion of biochemical deficiency was associated with consumption of vitamin B6 and zinc at the RDA level. Because little evidence of deficiency was observed with elevated intake in both groups, an effective program of nutritional supplementation may be beneficial in maintaining adequate plasma nutrient levels. PMID- 8199418 TI - Differential effect of bone marrow protein on brain ATPase of immunized control and malnourished rats. AB - After sheep erythrocyte (SRBC) immunization in balanced-diet-fed (BDF) rats, the brain microsomal ATPase activity for the first 48 h was suppressed compared with preimmunization level, then stimulated at the peak of the immune response. In contrast, rats malnourished by deprivation of vitamin B complex and ascorbic acid and with significantly lower pre- and postimmunization enzyme activity than the BDF rats, had stimulated enzyme activity only on immunization, and their immune response was found to be suppressed. A bone marrow-derived bioimmunomodulator (BIM) revived the immunocompetence of the malnourished immunized animals, and brain ATPase activity in these animals after BIM injection followed a pattern similar to that of the immunized BDF rats. We suggest that, after SRBC immunization under the influence of BIM, suppression followed by stimulation of the brain microsomal ATPase might be related to immune response. PMID- 8199419 TI - Liver lipid composition and intravenous, intraperitoneal, and enteral administration of intralipid. AB - We studied the variations arising in plasma and liver lipids after intravenous (i.v.), intraperitoneal (IP), and intragastric (IG) administration of a fat overdose on the order of 4 g.kg-1 body wt.day-1 in the form of Intralipid (ITL) 20% to 33 New Zealand rabbits for 15 days. The control group was submitted for surgery but did not receive an ITL supplement. The results show weight gain in all animals and normal liver enzyme values. There was an increase in plasma lipids in groups supplemented by the parenteral route (i.v. and IP), and fatty acids showed a similar distribution, in terms of percentages, to that for ITL. In liver tissue, there was an increase in the fractions related to ethanolamine and a decrease in phospholipids of choline and serine. In the i.v. group, neutral lipids predominated compared with other groups. The livers of all supplemented animals (i.v., IP, and IG) showed a higher content of stearic and linoleic acid and a reduction in oleic acid. Study with optical microscopy showed a microvacuolization affecting the three areas of the hepatic acini in the i.v. group, seen with electron microscopy as vacuoles lacking membranes and surrounded by mitochondria. In conclusion, there is an increase in hepatic steatosis in parenteral groups and a greater deposit of neutral lipids in the i.v. group, related to the administration route, without biochemical signs of liver dysfunction. PMID- 8199420 TI - Influence of dietary fiber on microbial growth in vitro and bacterial translocation after burn injury in mice. AB - Translocation of enteric bacteria from the gut to the mesenteric lymph nodes and beyond can cause life-threatening infection and multiple-organ failure in immunocompromised and traumatized patients. One of the conditions that promotes bacterial translocation is disruption of the normal gut flora, which results in bacterial overgrowth. In vitro methods were used to determine whether the fibers pectin, cellulose, chitosan, kaolin, lignin, or soy had bactericidal properties. Our results indicated that only chitosan and lignin significantly reduce microbial growth in vitro. A burned mouse model (20% total-body surface area) was used to study the effects of dietary lignin, cellulose, pectin, and chitosan on burn-induced bacterial translocation. Animals were fed a standard mouse diet containing no fiber, pectin, cellulose, lignin, or chitosan (10% of diet) for 14 days ad libitum. On day 14, all animals were burned. Four hours later the animals were killed and the mesenteric lymph nodes, spleen, liver, and cecum were aseptically harvested for determination of quantitative aerobic microbial growth. The animals which received chitosan, and lignin to a lesser extent, added to their diet had significantly lower levels of bacteria in the cecum, mesenteric lymph nodes, and liver. We suggest that addition of chitosan and possibly lignin to the diet may reduce the amount of bacterial translocation after burn injury, presumably by reducing the bacterial population of the cecum. PMID- 8199421 TI - Nutritional management of a patient with short-bowel syndrome and large-volume jejunostomy output. AB - Nutritional therapy of a patient with approximately 100 cm of remaining jejunum, severe malabsorption, and high jejunostomy output is presented. A high-calorie diet, oral rehydration therapy, and vitamin and mineral supplementation were used effectively to maintain a reasonable nutritional state without the need for long term intravenous therapy. PMID- 8199422 TI - "Occupational" exposure of infants to toxic chemicals via breast milk. AB - The transfer of toxic chemicals to breast milk represents an important, although not widely recognized, chemical exposure route for the infant. For an increasing number of nursing mothers who resume their professional activities after giving birth, the obvious benefits of breast-feeding must be evaluated versus the risk of the lactational transfer of occupational chemicals to the infant. In this article, we review qualitative and quantitative data on occupational chemicals that may contaminate the breast milk of lactating women in the work force, and we discuss the possible use of physiologically based pharmacokinetic models to aid in the assessment of risk for infants whose mothers are occupationally exposed to chemicals. PMID- 8199423 TI - Peripheral intravenous nutrition. PMID- 8199424 TI - Metabolic effects of hypoglycemic counterregulation during sustained mild hyperinsulinemia and constant glucose availability in healthy men. AB - Posthypoglycemic metabolic changes have been studied predominantly during waning of insulin action. We evaluated the effects of hypoglycemic counterregulation on glucose and lipid metabolism during continuous insulin infusion. Glucose was infused at a constant rate throughout the study (4 mg.kg-1.min-1). During the second part of the study, plasma glucose levels were clamped at approximately 4 mM by variable insulin infusion. In six subjects, but not in five control subjects, short-term hypoglycemia (nadir plasma glucose 2.80 +/- 0.05 mM) was induced by an additional bolus injection of insulin before starting insulin infusion. Substrate oxidation rates and plasma substrate fluxes were determined by indirect calorimetry and primed continuous infusions of [3-3H]glucose and [14C]palmitate. After hypoglycemia, higher insulin infusion rates than in the control group were required to clamp plasma glucose concentrations at similar levels (p < 0.05). Additionally, insulin levels were increased compared with those in control subjects (p < 0.01). There were no differences in substrate oxidation rates, hepatic glucose production, or lipolysis after hypoglycemia. In conclusion, the counterregulatory hormonal response after short-lasting mild hypoglycemia with sustained modest hyperinsulinemia and constant glucose availability induces insulin resistance with respect to glucose uptake but is unable to stimulate hepatic glucose production or lipolysis. PMID- 8199426 TI - Zinc requirement of premature infants. AB - Premature infants require adequate amounts of zinc to foster growth and cognitive development. Zinc given during TPN (450-500 micrograms.kg-1.day-1) is the only way to meet in utero accretion rates before 36 wk postconceptional age because of extensive resecretion into the gut of oral zinc. After that time, infants should be consuming formulas supplemented with 12 mg/L zinc for the whole of infancy. PMID- 8199425 TI - Utilizing laboratory parameters to monitor effectiveness of nutritional support. PMID- 8199427 TI - Calcium and phosphorus needs of premature infants. AB - Interpretation of the available studies for the purpose of predicting the recommended Ca and P needs of LBW infants is difficult because of the number of confounding variables that can affect Ca and P metabolism. Clinically, the most important measure of Ca/P "adequacy" must also be determined. Clearly, the predicted recommended intakes for dietary Ca and P would be different if normalization of serum and urine Ca and P levels is chosen rather than achievement of intrauterine retention of mineral or bone mineral content as the index of adequacy of mineral intake. The factorial approach to the estimation of Ca/P requirements was previously proposed by Ziegler et al. A reevaluation of their estimation is warranted in the light of recent data on estimates of fetal accretion of minerals in the third trimester (2.9 used by Zeigler et al.) vs. 3.7 estimated by Widdowson et al. and reported efficiencies of absorption of various sources of Ca and P in feedings for LBW infants. Based on the observed differences in bioavailability of Ca and P from different salts and combined with various milks, it may be appropriate to recommend intakes of Ca and possibly P that are specific for premature formulas separate from that recommended for supplements to preterm mother's milk. PMID- 8199428 TI - Protein in premature feeding. PMID- 8199429 TI - Biochemical and functional approaches to study of fatty acid requirements for very premature infants. AB - Plasma and RBC omega-6 and omega-3 fatty acids reflect the composition of these fatty acids in the diet, and their analyses seem unlikely to add little more to studies on infant fatty acid requirements than evidence that the milk or formula diet was adhered to. Tests of visual function, cognitive, and motor skill development, however, are sufficiently sensitive to demonstrate significant differences between groups of infants fed diets that differ only in fatty acid composition. These functional tests offer the potential for future research with modified formulas or expressed milk to determine not only fatty acid requirements but also to further fundamental understanding of the role of specific omega-6 and omega-3 fatty acids in CNS development and function. PMID- 8199430 TI - Iron requirements of preterm infants. PMID- 8199431 TI - Zinc and immunity. PMID- 8199432 TI - Integration of Latin America in the world of nutritional support. PMID- 8199433 TI - Current concepts in clinical nutrition: role of the dietitian. PMID- 8199434 TI - Taurine and TPN solutions? PMID- 8199435 TI - Intraperitoneal nutrition. PMID- 8199436 TI - The renaissance of peripheral intravenous feeding. PMID- 8199437 TI - Monitoring nutritional support. PMID- 8199438 TI - Nutrition status and the laboratory. PMID- 8199439 TI - Competitive inhibition between large neutral amino acids at cell membrane of phenylketonuria patients. PMID- 8199440 TI - Clinton health-care reform.... A transformation of the academic medical center. PMID- 8199441 TI - Why 5%? PMID- 8199442 TI - Fat emulsions for complete intravenous nutrition. 1967. PMID- 8199443 TI - Epidemiology of tumors affecting the visual system. AB - Cancer is a leading cause of morbidity and the second leading cause of mortality in the United States. The eye and adnexa are potential foci of neoplastic disease, either as primary sites or as sites of metastatic carcinoma. The most frequent anatomical site of ocular cancer is the eye, followed by the orbit, the conjunctiva, and the lacrimal gland. The average annual age-adjusted incidence of ocular cancer varies between 0.6 per 100,000 and 0.9 per 100,000 for the male population and between 0.5 per 100,000 and 0.8 per 100,000 for the female population. The distribution of eye cancer risk by age is bimodal, with peaks occurring during early childhood and again during adulthood. Retinoblastoma is the most common ocular malignancy in children, and uveal melanoma is the most common ocular malignancy in adults. PMID- 8199444 TI - Pituitary adenoma. AB - Pituitary adenoma is the most common intracranial tumor that affects the visual system. A variety of signs and symptoms of disease may be produced, either ocular or endocrine, depending on the type of tumor involved. Nonfunctional pituitary adenomas show no elevation in serum hormone concentration and produce visual symptoms that result from the compression by the tumor mass of adjacent structures. These tumors are more likely to be diagnosed by an ophthalmic clinician than functional adenomas, which cause endocrine dysfunction and are more likely to be diagnosed by an endocrinologist. Diagnostic imaging and clinical laboratory testing may be used to confirm the presence of the tumor. Treatment for pituitary adenoma includes medication, radiotherapy, surgery, or a combination of these options. PMID- 8199445 TI - Brain tumors, malpractice, and optometry. AB - Intracranial tumors affecting the visual system are a source of malpractice claims involving optometrists. Signs and symptoms of disease, such as papilledema, optic atrophy, decreased visual acuity, headache, loss of visual field, acute onset incomitant strabismus, and gradually worsening coordination, should prompt optometrists to rule out the possibility of an underlying intracranial lesion. Appropriate optometric and medical evaluation should be provided. Co-management of care with other health care practitioners should be scrupulously coordinated and documented. PMID- 8199447 TI - Headache. PMID- 8199446 TI - Extraocularmotor dysfunction associated with tumors. AB - Intracranial and extracranial tumors can be the cause of extraocularmotor dysfunction. In approximately 19% of reported cases, paralysis of the third, fourth, or sixth cranial nerves is due to neoplastic growth; the sixth nerve is the most commonly affected. Tumors can produce extraocular muscle dysfunction by directly affecting the extraocular muscle; directly affecting the third, fourth, or sixth cranial nerves; directly affecting the supranuclear extraocular movement areas; indirectly affecting any of the above by metastasis from a tumor in another part of the body; and indirectly affecting the third, fourth, or sixth cranial nerves or their nuclei or the supranuclear extraocular movement areas through an increase in intracranial pressure. The ocular signs and symptoms of disease vary based on the mechanism involved. PMID- 8199448 TI - Basal cell and squamous cell carcinomas. AB - Basal cell and squamous cell carcinomas are actinic lesions that must be considered in the differential diagnosis of growths of the eyelid. Basal cell carcinoma is the most common eyelid cancer. It tends to grow slowly, and rarely if ever metastasizes. Basal cell carcinoma can, however, grow by direct extension to adjacent structures including the brain. Basal cell carcinoma can be managed by Moh's surgery, excision, cryosurgery, radiation, and chemotherapy. Squamous cell carcinoma has similar epidemiology to basal cell carcinoma. However, it grows much faster and it can metastasize (up to 20% of the time). It is best managed by conventional surgery, cryosurgery, and sometimes radiation. Squamous cell carcinoma can have a grim prognosis if not detected and treated promptly. PMID- 8199449 TI - Clinical diagnosis of tumors of the conjunctiva. AB - Tumors of the conjunctiva are easily visible to professional and lay observers. Because of this, they are frequently a source of patient self-referral. These lesions range from benign to malignant, and a differential diagnosis often requires the collaboration of the surgeon and pathologist as well as the diagnosing clinician. This article reviews the spectrum of conjunctival lesions based on how they appear to the clinician, with brief guidelines regarding management. PMID- 8199450 TI - Retinoblastoma. AB - Retinoblastoma is the most common primary intraocular tumor of childhood. The most common presenting sign of retinoblastoma is leukocoria; the second most common presenting sign is strabismus. The optometrist's ability to recognize the presenting signs and symptoms of retinoblastoma can lead to early diagnosis and expeditious treatment. Treatment modalities include enucleation, radiotherapy, cryotherapy, photocoagulation, and chemotherapy. Goals of treatment include patient survival and preservation of vision. Cooperation of the optometrist, the ophthalmologist, the ophthalmic nurse, the pediatric oncologist, and the radiation therapist plays an important role in the long-term survival of these children. PMID- 8199451 TI - Choroidal malignant melanoma. AB - Choroidal nevi are found on routine fundus evaluations in 1% to 2% of patients. It is felt that these usually benign lesions are the precursors of choroidal malignant melanomas. The incidence of choroidal malignant melanoma in the United States is approximately 6 cases per 1 million persons per year. Diagnosis is multifactorial, based on the tumor's funduscopic, angiographic, and ultrasonographic appearance. Once a melanoma is diagnosed in a patient, a complete metastatic workup is performed. A small tumor is observed for change. Medium-sized tumors are treated with radioactive plaque therapy, external beam radiation, or enucleation. Large tumors are treated with enucleation with or without external beam radiation. Studies are underway to establish the optimum form of treatment. PMID- 8199452 TI - Ocular metastatic disease. AB - Metastasis to the eye represents by far the most common form of intraocular and orbital cancer. This form of malignant disease may present with a variety of signs and symptoms including pain, vision loss, visual field defect, and proptosis. This varied clinical presentation is described, and available treatment modalities are discussed. PMID- 8199453 TI - Does Yersinia induce autoimmunity? AB - Yersinia enterocolitica O:3 and the human thyrotropin receptor share a structural similarity, revealed by their serological cross-reactivity. The exact molecular basis of the similarity is open. In spite of this cross-reactivity, Yersinia seems not to be a major inducer of thyroid autoimmunity. Yersinia infections or avirulent Yersinia strains in the intestinal flora may rather contribute to the development of thyroid autoimmunity arising for other reasons in genetically susceptible individuals. Regarding Yersinia and spondyloarthropathies, it is undetermined whether the chronic sequelae of acute Yersinia-triggered reactive arthritis are due to the persistence of phlogistic microbial components or to autoimmunity, or to both. No convincing evidence exists for a role of molecular mimicry between Yersinia and HLA B27 or other host structures. Cytotoxic T-cell clones derived from synovial fluid, and capable of killing Yersinia-infected and uninfected autologous targets in an HLA B27-restricted fashion have recently been described. Evaluation of their significance for the potential Yersinia-induced autoimmunity is waiting for characterization of the bacterial and host peptides involved. PMID- 8199454 TI - New directions for biological therapy in rheumatoid arthritis. AB - Advances in our understanding of the pathogenesis of rheumatoid arthritis (RA), together with developments in hybridoma and molecular technology have opened the way for more directed therapy in this disease. In reviewing the experience so far with T-cell-directed biological agents, we show that the early promise displayed by anti-CD4 monoclonal antibodies in open clinical trials has not been sustained in controlled studies. This outcome provides a challenge to the concept that CD4+ T cells are of prime importance in RA, and prompts a search for alternative therapeutic targets. Agents directed towards other leucocyte antigens such as CD5, CDw52 or the receptor for interleukin 2 have induced clinical responses in early studies, but at the expense of significant toxicity. Newer therapies targeting the monokines tumour necrosis factor alpha (TNF-alpha), IL-1 and IL-6, and the leucocyte adhesion molecule intercellular adhesion molecule 1 (ICAM-1) have provided encouraging clinical improvements and, in the case of anti-TNF alpha and anti-IL-6, impressive modulation of the acute-phase response. Strategies allowing long-term blockade of such molecules, including antibody reshaping and the use of soluble cytokine receptors are discussed. Finally, the potential for using biological agents in combination with other therapies is outlined. PMID- 8199455 TI - Dioxins and the immune system: mechanisms of interference. A meeting report. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin, or simply 'dioxin', is an environmental pollutant, infamous for its extremely high toxicity. Dioxin mimics the unknown natural ligand of the cytosolic arylhydrocarbon receptor which is conspicuously abundant in the thymus, and acts as a transcription factor upon ligand engagement. Thymus atrophy and immunosuppression have long been known to be major effects of dioxin exposure, evident at even very low doses. In a meeting held in Dusseldorf, FRG, the immunotoxicology of dioxin was discussed with respect to the pathomechanisms of dioxins on lymphocyte stem cells, thymus and T cells, cytokine modulation, and other components of the immune system. Such immunological insults may have consequences for the risk assessment of chemical compounds like dioxin. PMID- 8199456 TI - Antiendothelial cell antibodies in systemic lupus erythematosus: enhanced antibody binding to interleukin-1-stimulated endothelium. AB - IgG antiendothelial antibodies (IgG AEA), as measured by enzyme-linked immunosorbent assay, could be detected in serum samples of 38 out of 41 patients with systemic lupus erythematosus. Incubation of endothelial cells (EC) with interleukin-1 alpha (IL-1 alpha), in contrast to incubation with interferon gamma or tumor necrosis factor alpha, resulted in an enhanced IgG AEA binding. Immunoblotting revealed reactivity of AEA against a variety of EC antigens. The upregulation of IgG-AEA-binding reactivity to IL-1 alpha-stimulated EC was due to binding to antigens that were already expressed by unstimulated EC. The IgG binding reactivity to both IL-1 alpha-stimulated and unstimulated EC was significantly higher in the serum of patients with joint or skin abnormalities as compared with patients without these manifestations. These data suggest that upregulated binding of IgG to EC induced by IL-1 alpha may play a role in immune vascular damage. PMID- 8199457 TI - Occurrence of IgG subclass antibodies to ovalbumin, avidin, and pneumococcal polysaccharide in children. AB - The serum levels of the four subclasses of IgG to three different antigens- ovalbumin (OVA), pneumococcal polysaccharide (PNC), and avidin--were determined by enzyme-linked immunosorbent assay in three age groups of healthy children: 1.2 2.5 years (group A, n = 20), 6-7 years (group B, n = 21) and 15-17 years (group C, n = 20). The anti-OVA response in all groups was dominated by IgG1, IgG2, and IgG4 antibodies which generally increased in levels from group A to group B, but then declined significantly in group C. In all age groups, the IgG2 and IgG4 as well as the IgG1 and IgG3 responses were correlated; an association was also observed between IgG1 and IgG2 in groups B and C, but not in group A. The anti PNC response was restricted to the IgG2 and IgG4 subclasses; correlation between these subclasses was seen only in group B children. The more predominant IgG2 antibodies increased dramatically in concentration from group A to group B, and then less remarkably in group C. Occurrence of the IgG1 anti-PNC antibodies was different which resembled the anti-OVA response. Responses to avidin, a protein derived from the same source as OVA, were different from the anti-OVA responses. These were low and confined to the IgG1 and IgG2 subclasses only and mainly to the younger children. A small group (n = 8) of 6- to 7-year-old atopic children who had a history of asthma or eczema appeared to have responses similar to their healthy counterparts. PMID- 8199458 TI - Antibodies to dietary antigen in serum from patients with sickle cell anemia. AB - The levels of antibodies of the IgG, IgA and IgM isotypes reacting against ovoalbumin (OVA), gliadin (GL) and cow's milk proteins (CMP), were determined by ELISA in sera from a group of adult patients with sickle cell anemia (SCA) bearing homozygous Ss hemoglobinopathy and from matched health donors. Only patients with steady-state disease were included in the study. Increased amounts of IgG and IgA reacting with OVA, GL and CMP were observed in the group of patients as compared with the controls. In contrast, the levels of IgM antibodies against each of the three dietary antigens were similar in patients and controls. Increased levels of IgG and IgA antibodies against dietary antigens in SCA may result from enhanced permeability of the gut mucosa to macromolecules of dietary origin as a consequence of microinfarctions, chronic polyclonal B cell activation and/or diminished inhibitory control of antibody synthesis. PMID- 8199459 TI - Quantitation and immunocytological identification of interleukin-1 in nasal polyps from patients with chronic sinusitis. AB - Immunoreactive interleukin-1 (IL-1) alpha and beta levels in nasal polyp (NP) extracts were measured from 22 adult patients with chronic sinusitis (CS) in order to determine their significance in the pathogenesis of NP. The NP sample was separated into mononuclear and polymorphonuclear fractions. In the mononuclear fraction, the mean value of IL-1 beta was 21.5 pg/ml/g, which was significantly higher than that of IL-1 alpha (8.4 pg/ml/g, p < 0.01). In younger adults, the IL-1 alpha and IL-1 beta levels were 21.2 and 59.4 pg/ml/g, which were significantly higher than those in older CS patients (p < 0.01). There was a significant reverse correlation between patient's age and IL-1 beta levels in the mononuclear fraction (r = -0.509, p < 0.01). Immunoreactive IL-1, mainly IL-1 beta, was identified in the cytoplasmic area of monocytes. A certain amount of immunoreactive IL-1 is produced in mononuclear leukocytes, particularly activated monocytes, and IL-1 beta production is greater than IL-1 alpha. In younger adult CS patients, NPs contain larger amounts of IL-1 beta in monocytes, compared to those of older patients. PMID- 8199460 TI - Identification of alpha-amylase inhibitor as a major allergen of wheat flour. AB - We isolated a major wheat flour allergen with a molecular weight of 15-kD. The 15 kD allergen was purified from an extract of wheat flour by ammonium sulfate precipitation followed by gel filtration. Using the immunoblot technique, IgE, specifically directed towards the single isolated allergen, was detectable in 50% of the applied sera. We determined the N-terminal amino acid sequence of the allergen and identified it as an alpha-amylase inhibitor protein. Our data emphasize that low molecular weight wheat flour allergens play an important role in the pathogenesis of baker's asthma disease. PMID- 8199461 TI - Fusarium solani: immunochemical characterization of allergens. AB - Allergenic components of the fungus Fusarium solani were isolated using (NH4)2SO4 precipitation and ion-exchange column chromatography. The allergenicity of fractions was studied by enzyme-linked immunosorbent assay and radioallergosorbent test inhibition techniques. Proteins of culture filtrate (CF), mycelium (MY), and spore (SP) extracts of F. solani were characterized by isoelectrofocusing, sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and IgE-specific immunoblotting. CF antigen of F. solani contained more allergenic proteins than MY and SP, visible on immunoblot analysis using allergenic serum pool. A 65-kD protein component of CF was found to be a major allergen, as it was strongly visible on immunoblots of all 15 patient sera tested. Crossed immunoelectrophoresis and enzyme-linked immunosorbent assay inhibition using rabbit antibodies raised against F. solani CF demonstrated shared antigenicity between CF, MY, and SP extracts. It was observed that F. solani is a significant allergen, and most of the allergens of MY and SP extracts were found in CF extract. Therefore, CF alone can be used in the preparation of a standard extract. However, few unique allergenic proteins were observed in MY as well as in SP extracts of F. solani. Hence, the use of combined CF, MY, and SP extracts of F. solani is recommended for diagnosis and immunotherapy. PMID- 8199462 TI - Allergens in hymenoptera venom. XXVI: The complete amino acid sequences of two vespid venom phospholipases. AB - The 2 major allergenic proteins in vespid venoms are antigen 5s and phospholipases (PLs). Vespid PLs have a molecular weight of about 34,000 and have been previously shown to have an A1B specificity, unlike the A2 specificity of bee PLs. The complete amino acid sequences of the venom PL from the yellow jacket, Vespula maculifrons, and the more acidic isoenzyme from the white faced hornet, Dolichovespula maculata, have been determined by sequencing overlapping peptides isolated from enzyme and chemical digests of the proteins. Ves m 1 is composed of 300 amino acids, with variants found at 3 positions. Dol m 1.02 is composed of 303 amino acids with variants at 2 positions. Comparison with the sequence of Dol m 1.01 determined by cDNA sequencing gave 66.7% identity with Dol m 1.01 with almost all variation in the first 131 positions. Ves m 1 showed 69% identity with Dol m 1.01 and 38.7% with Dol m 1.02. Comparison of the PL sequences with the Protein Identification Resource data base showed many similarities with the lipase family, but very little relationship to known PLs. The amount of structural similarity between Dol m 1 and Ves m 1 is similar to that found among antigen 5 molecules of different genera, and is sufficient to account for antigenic cross-reactivity. There appear to be a number of highly conserved regions of the PL molecules, especially in the C-terminal 168 residues. These regions may from common epitopes found in several species and genera of vespids. Antibodies against these common epitopes will not be able to distinguish among PLs from various vespids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199463 TI - Abnormal IgG4 antibody response to aeroallergens in allergic patients. AB - Various studies have suggested the involvement of immunoglobulin G4 (IgG4) antibodies (Ab) in the physiopathology of allergic disorders. Recently, an abnormal IgG4 Ab production in response to immunization has been reported in some atopic patients. Thus, in order to evidence in allergic patients, a potential abnormal IgG4 Ab response to aeroallergens following natural exposure, we compared, in 34 patients sensitive to Dermatophagoides pteronyssinus and in 16 healthy subjects, the IgG4 Ab response to D. pteronyssinus, grass pollen and cat dander, using a solid-phase radioimmunoassay. Since some patients were also sensitive to grass pollen and/or to cat dander, we analyzed, in all patients, the IgG4 Ab responses both towards the allergen(s) they were sensitive to (sensitizing allergen) or not (unrelated allergen). The results showed that 90% of the patients produced levels of antisensitizing allergen(s) IgG4 Ab significantly higher than the controls; this IgG4 Ab response was correlated with the corresponding specific IgE Ab level. In addition, among these patients, around 40% presented high levels of IgG4 Ab to the unrelated allergen(s). Thus, in allergic patients, while specific IgE Ab define the nature of the sensitizing allergen, the presence of IgG4 Ab directed against various allergens seems in relation with an abnormal isotype regulation associated with atopic disorders. PMID- 8199464 TI - Different pattern of IgE binding to chicken egg yolk between patients with inhalant allergy to birds and food-allergic children. AB - IgE binding antigens in budgerigar, canary and parrot serum were analyzed by immunoblotting. With 4 sera from patients with a respiratory allergy to birds, a closely related pattern of IgE binding to SDS-PAGE separated sera of the 3 birds was found. In all 3 bird sera a major IgE binding structure was present with a MW of about 60 kD. The pattern of IgE binding to SDS-PAGE separated egg yolk in sera from the patients allergic to birds, was different from sera of food-allergic children. Whereas in the bird-allergic patients major IgE binding occurred to a 60 kD component in egg yolk, IgE from food-allergic children was preferentially bound to a 35-kD structure in egg yolk. PMID- 8199465 TI - Binding properties of protein A and protein G for human IgE. AB - We studied the binding of protein A and protein G to human monoclonal and polyclonal IgE. An ELISA was used to measure human IgE. Protein A-Sepharose did not bind to monoclonal IgE, but bound to 12-14% of serum polyclonal IgE and to 3% of the polyclonal IgE purified from the serum. No difference in binding to protein A was found between IgE from an allergic patient and that from a non allergic subject. Protein G bound to neither polyclonal IgE nor monoclonal IgE. Thus, protein G is better than protein A with respect to separation of IgE from IgG. PMID- 8199466 TI - Arylsulfatase B is present in crystalloid-containing granules of human eosinophil granulocytes. AB - Eosinophil granulocytes are characterized by large crystalloid-containing granules whose major contents of highly cationic proteins may play a role in allergic reactions and parasitic infections. Human eosinophils are also rich in arylsulfatase B whose enzymatic activity is localized to a population of small type cytoplasmic granules and used as a marker for such organelles. We utilized immunoelectron microscopy to investigate its subcellular distribution in human eosinophils. The arylsulfatase B antigen was found to be concentrated to both the crystalloid core and the matrix of crystalloid-containing granules as well as in small type granules. Therefore arylsulfatase seems to be present primarily in crystalloid-containing granules in a possibly inactive form (but detected by antibodies) that is converted to an enzymatically active form, e.g. during secretion and formation of small type granules which may derive from the former granules. PMID- 8199467 TI - The AOAC official methods for detection of staphylococcal enterotoxins in foods. PMID- 8199468 TI - Determination of tylosin and tilmicosin residues in animal tissues by reversed phase liquid chromatography. AB - A method for the simultaneous determination of tylosin and tilmicosin residues in animal tissues is reported. Solid-phase extraction columns are used to isolate the drugs from tissue extracts. Determination is accomplished by reversed-phase liquid chromatography with UV detection at 287 nm. Mean recoveries from spiked tissues were 79.9% (coefficient of variation [CV], 8.1%) for tylosin and 92.6% (CV, 8.7%) for tilmicosin. Detection limits for tylosin and tilmicosin were 0.020 and 0.010 ppm, respectively. PMID- 8199469 TI - Simultaneous determination of nitrofurazone, nitrofurantoin, and furazolidone in channel catfish (Ictalurus punctatus) muscle tissue by liquid chromatography. AB - A liquid chromatographic (LC) method was developed for the simultaneous determination of nitrofurazone (NFZ), nitrofurantoin (NFT), and furazolidone (FZD) in catfish muscle tissue. The drugs were extracted from the tissue with acetonitrile, and the lipids were removed from the extract with hexane. The acetonitrile extract was evaporated by rotary evaporation, and the resultant drug residues were dissolved with LC mobile phase. The mixture was sonicated, centrifuged, and filtered. The drugs were determined by using LC with a C18 reversed-phase (ODS Hypersil) column, a mobile phase of acetonitrile-1% aqueous acetic acid (25 + 75), and a photodiode array ultraviolet detector at 375 nm. NFZ, NFT, and FZD were each determined in catfish tissue at 5 fortification levels (80, 40, 20, 10, and 5 ng drug/g tissue). Average recoveries of each of the 3 drugs at each level ranged from 70.7 to 101.5%, and relative standard deviations ranged from 2.2 to 18.6%. The limit of detection of each drug was approximately 1 ng drug/g tissue, and the limit of quantitation was 5 ng drug/g tissue. In the second part of the study, the method was used to determine nitrofuran residues incurred in catfish tissue. Live channel catfish were intravascularly doses (10 mg/kg body wt) with NFZ to generate drug-incurred fish muscle tissue. Incurred NFZ levels exceeded 400 ng drug/g tissue at 2 h after dosing but decreased rapidly to approximately 1 ng drug/g tissue by 8 h after dosing, as determined by this method. PMID- 8199470 TI - Iron milk medium method for recovering Clostridium perfringens from shellfish: collaborative study. AB - Eleven laboratories participated in a collaborative study analyzing shellfish (oysters, Crassostrea gigas) for the detection and enumeration of Clostridium perfringens by the iron milk medium (IMM) method. The IMM method was compared to AOAC Official Method 976.30. Shellfish were artificially inoculated with C. perfringens cells (vegetative and spores) at low (1 x 10(3) colony forming units [cfu]/g), medium (1 x 10(4) cfu/g), and high (1 x 10(6) cfu/g) levels. Negative controls (zero level) were analyzed by each laboratory. C. perfringens FD-1, the strain involved in a foodborne illness, was used. Blind duplicates of each inoculum level were analyzed, giving a total of 16 samples per laboratory. The selectivity of IMM relies solely on the rapid growth of C. perfringens at 45 degrees C indicated by stormy fermentation reaction within 18 h. C. perfringens is detected and enumerated using the most probable number technique. A statistical evaluation of the data found no significant differences between the estimates from the 2 methods. The IMM method for detection of C. perfringens from shellfish has been adopted first action by AOAC INTERNATIONAL. PMID- 8199471 TI - Visual screening with enzyme immunoassay for staphylococcal enterotoxins in foods: collaborative study. AB - Selected foods containing 4-10 ng each of a mixture of Staphylococcus aureus enterotoxin serotypes A-E were tested by 15 collaborators. An enzyme-linked immunosorbent assay (EIA) was used with polyvalent antisera to these serotypes in a polyclonal antibody double "sandwich" configuration. Controls were free of toxin. Foods (25 g test samples) were homogenized with Tris (0.25 M, pH 8.0) and centrifuged. The food extract was filtered through cotton and mixed with sample additive. For the EIA, 200 microL aliquots of the treated extracts were added to previously washed microtiter wells coated with antibody to staphylococcal enterotoxin serotypes A-E. Wells were washed and treated with the polyvalent antisera (A-E)-enzyme conjugate, and then washed again. Substrate was added, and wells were incubated. After incubation, stop solution was added. Results were determined visually and by measuring absorbance using a microtiter plate reader. In foods containing enterotoxin, bluish-green color was developed (positive result). Test solutions with absorbances > 0.200 were considered positive; those with absorbances < or = 0.200 were negative. The method is sensitive and specific, and allows the rapid assay of staphylococcal enterotoxins in foods without differentiating their serotypes. The method has been adopted first action by AOAC INTERNATIONAL. PMID- 8199472 TI - Salmonella detection in cocoa and chocolate by motility enrichment on modified semi-solic Rappaport-Vassiliadis medium: collaborative study. AB - A collaborative study was performed in 13 laboratories (including the authors' laboratories) to validate motility enrichment on modified semi-solid Rappaport Vassiliadis (MSRV) medium for rapid detection of motile Salmonella in cocoa powder and chocolate. The MSRV method was compared with the AOAC standard culture method for detection of Salmonella in cocoa powder, milk chocolate, sweet chocolate, and dark chocolate. Chocolate samples were artificially inoculated with Salmonella at 2 levels of contamination. Cocoa powder was inoculated at 2 levels with naturally contaminated dust from cocoa beans. Uninoculated control samples were also included for each type of product. The sensitivity rate was 98.1% for the MSRV method and 94.9% for the AOAC culture method. The specificity rate was 100.0% for both methods. There was no significant difference in the proportion of samples positive by MSRV and the AOAC culture methods for any of the food types. The MSRV method has been adopted first action by AOAC INTERNATIONAL. PMID- 8199473 TI - Elevated-temperature, colorimetric, monoclonal, enzyme-linked immunosorbent assay for rapid screening of Salmonella in foods: collaborative study. AB - A collaborative study was performed by 30 laboratories in 3 sets of trials to validate a modified colorimetric monoclonal enzyme-linked immunosorbent assay (ELISA) method for Salmonella detection. The modifications to the current methodology included incubation of enrichments and post-enrichments at an elevated temperature, addition of novobiocin to the M-broth post-enrichment, and elimination of the centrifugation and agitation steps. Five artificially contaminated foods (nonfat dry milk, milk chocolate, dried egg, ground black pepper, and soy flour) and 1 naturally contaminated food (raw ground turkey) were analyzed. The artificially contaminated foods were inoculated with individual Salmonella serotypes at a high (10-50 cells/25 g) and low (1-5 cells/25 g) contamination level. Results from the modified ELISA method were compared to the Bacteriological Analytical Manual (BAM)/AOAC culture method. In 2 of the food products, milk chocolate and pepper, a number of laboratories isolated Salmonella from un-inoculated control samples, thus invalidating their data. As a result, there were too few laboratories remaining with valid data, and these foods were repeated. In the completed study, there were 11 false negative results obtained by the modified ELISA method, while there were 28 false negatives produced by the BAM/AOAC procedure. There were 11 ELISA positive assays which could not be confirmed by culture methods. Statistically, there were no differences between the modified, colorimetric, monoclonal ELISA and the reference culture method in all foods except raw turkey, where the ELISA method was more productive. The colorimetric monoclonal enzyme immunoassay (Salmonella-Tek) method for detecting Salmonella in all foods has been adopted first action by AOAC INTERNATIONAL. PMID- 8199474 TI - Determination of the presence of Listeria monocytogenes in milk and dairy products: IDF collaborative study. AB - A collaborative study was conducted on the recovery of viable Listeria monocytogenes from milk and dairy products (Camembert cheese, Limburger cheese, skim milk powder, and ice cream). Test portions were homogenized with Listeria selective liquid enrichment medium and cultured at 30 degrees C for 48 h. The enrichment culture was then subcultured onto a solid isolation medium at 37 degrees C for 48 h. Suspected Listeria colonies were identified by appropriate conventional morphological, physiological, and biochemical tests. Five kinds of dairy matrixes were spiked with L. monocytogenes at 2 levels: 12 and 120 colony forming units (cfu)/25 g. Each of the 18 collaborating laboratories analyzed 15 blind test portions from each matrix, comprising 5 replicates at each spiking level and 5 uninoculated controls, for a total of 1350 analyses. The specificity of the method was 100%; its sensitivity was 94-100% at the high spiking level and 89-98% at the low spiking level, except for Limburger cheese, which was only 68%. No specificity or sensitivity differences were observed between laboratories for all matrixes at the high spiking level and for all except Limburger cheese at the low spiking level. The calculated 50% detection limit for all products except Limburger cheese was 1.6 cfu/25 g; the 50% detection limit for Limburger cheese itself was 4.1 cfu/25 g. The method was adopted first action by AOAC INTERNATIONAL. PMID- 8199475 TI - Identification of hairs of three Asian commensal mammals: Suncus murinus, Bandicota bengalensis, and Rattus exulans. AB - Hairs of 3 major Asian commensal mammals, Suncus murinus (L.), Bandicota bengalensis (Gray and Hardwicke), and Rattus exulans (Peale), were studied, identified, and compared with those of better-known commensal species to provide an overview of their hair morphologies. Techniques were developed for authentic hair specimen collection and rapid slide mounting to aid in the timely analysis of food products. The study showed that hairs of B. bengalensis and R. exulans are easily identified to the regulatory category of "rat or mouse hair," whereas identification of S. murinus contaminant hairs is possible to the species level. PMID- 8199476 TI - Detection of adulteration in apple juice by L-malic/total malic acid ratio: collaborative study. AB - L-Malic acid is the predominate acid in pure apple juice and no D-malic acid should be present. Synthetic malic acid contains 50% D-malic acid, is inexpensive, and can be used to create nonauthentic apple juice. L-Malic/total malic ratios of 0.9 or less are indicative of a nonauthentic sample. Fourteen laboratories participated in a collaborative study to determine the L-malic/total malic acid ratio in apple juice. Ten samples of apple juice were sent to each laboratory. Authenticity of the samples varied from 0 to 100%. The coefficients of variation in all cases were acceptable, i.e., ca 5%. The method was adopted first action by AOAC INTERNATIONAL. PMID- 8199477 TI - Determination of 2-methoxy-3-alkylpyrazines in carrot products by gas chromatography/nitrogen-phosphorus detection. AB - The 2-methoxy-3-alkylpyrazines in 6 types of carrot products were determined by a stripping-selective trapping procedure followed by purge-and-trap gas chromatographic analysis with an NP detector. The aroma threshold of one of the principal pyrazines, 2-methoxy-3-sec-butylpyrazine, in a carrot medium was 0.19 ng/g. The concentrations of this compound in whole-carrot products were 0.43 (fresh), 0.291 (canned, cooked), and 0.224 ng/g (frozen). A diced, cooked, and freeze-dried product contained 0.070 ng/g. All of these products contained only this pyrazine. In contrast, a shredded, bagged product contained 2-methoxy-3 isopropylpyrazine as the sole pyrazine (0.32 ng/g), and a sliced, dried product contained a mixture of 3 pyrazines: 2-methoxy-3-sec-butyl- (0.109 ng/g), 2 methoxy-3-isopropyl- (0.176 ng/g), and 2-methoxy-3-isobutylpyrazine (0.029 ng/g). The pyrazine concentrations in most of these products (except the freeze-dried product) exceeded the threshold value. PMID- 8199478 TI - Rapid, sensitive, iron-based spectrophotometric methods for determination of peroxide values of food lipids. AB - The official International Dairy Federation method for determination of the peroxide value of anhydrous milk fat was extended to poultry, meat, fish, and vegetable oils. The ferrous oxidation-xylenol orange method for determination of peroxide values of liposomes and lipoproteins was modified to make it simpler and more rapid. These 2 spectrophotometric methods were used successfully to determine the peroxide values of beef, chicken, butter, fish, and vegetable products. The results in most cases were consistent with those obtained by using the AOAC Official Method. The spectrophotometric methods have an assay time of less than 10 min, require < or = 0.3 g fat, and are capable of determining peroxide values as low as 0.1 mequiv/kg of sample. PMID- 8199479 TI - Spectrophotometric determination of nitrate in baby foods: collaborative study. AB - A collaborative study was conducted of a spectrophotometric method for determination of nitrate after cadmium reduction to nitrite in baby foods containing meat. Thirty-one municipal and 2 industrial food laboratories participated in the study. The study design involved 2 baby food matrices. Samples of both matrices were prepared at 3 concentration levels between 52 and 309 mg NaNO3/kg as blind duplicates. A blank without added nitrate was also included. The outlier percentage of the results was very low (4.3%). It was typical for the method that recoveries were slightly > 100%. Recoveries for baby foods varied between 113.3 and 116.9%, and were acceptable for control purposes. The relative standard deviations for repeatability were 5.0-18.1%. The relative standard deviations for reproducibility were 8.3-21.6%. Three collaborators also evaluated liquid chromatographic technique for nitrate determinations. These preliminary results are presented but are not analyzed statistically. The spectrophotometric method was adopted first action by AOAC INTERNATIONAL. PMID- 8199480 TI - Effect of infrared analyzer homogenization efficiency on linearity of uncorrected fat A and fat B signals. AB - The objective of the survey was to determine if poor homogenizer performance causes nonlinear behavior of the uncorrected fat A or fat B signal that is not detected when an instrument's residual nonlinearity is determined by using dilutions of homogenized milk instead of unhomogenized milk. Unhomogenized and homogenized (17238 kPa) portions of the same 6.1% fat milk were tested on 20 instruments to determine homogenization efficiency. Instruments with differences of > or = 0.087% fat between homogenized and unhomogenized portions of the same milk had inefficient homogenization, on the basis of criteria established in a previous study. Four and 12 instruments out of 20 demonstrated inefficient homogenization for the fat A and fat B channels, respectively. Uncorrected signal linearity for the fat channels was evaluated quantitatively by using a series of dilutions of homogenized (17238 kPa) and unhomogenized milks. Most instruments passed the linearity evaluation for dilutions of either homogenized or unhomogenized milk, even though many of the same instruments failed the homogenization efficiency evaluation. Thus, using dilutions of homogenized milk is valid for linearity evaluation of instruments being used for testing unhomogenized milk in the range of fat concentrations used for payment testing. PMID- 8199482 TI - Sensitivity of the quick color test for indicating lead release from ceramicware. AB - A quick color test (QCT) for indicating the presence of leachable Pb on ceramicware was evaluated as a screening tool. Fourteen sets of cups and mugs (197 pieces) of undecorated glazed ceramicware were tested. The QCT indicated the presence of leachable Pb on 95% of the cups and mugs at or above approximately 2 micrograms/mL. The QCT is an inexpensive and rapid qualitative test for Pb that can be conducted with a portable kit. PMID- 8199481 TI - Determination and speciation of arsenic in human urine by ion-exchange chromatography/flow injection analysis with hydride generation/atomic absorption spectroscopy. AB - A flow injection-hydride generation/atomic absorption spectroscopic method for the measurement of total urinary arsenic and for the selective determination of inorganic arsenic, monomethylarsonic acid (MMAA), and dimethylarsinic acid (DMAA) was developed. Destruction of the organic matrix is necessary to measure total arsenic content of urine samples. Digestion of this matrix with HNO3-H2SO4-H2O2 is described. The separation of inorganic, monomethylated, and dimethylated arsenic compounds in urine was performed with ion-exchange chromatography on AG 50 W-X8 resin. Detection limits of 2 ppb for each arsenic form and of 3 ppb for total arsenic in urine analyzed after mineralization were found. Recoveries in triplicate urine samples spiked with 10 ppb inorganic arsenic, 20 ppb MMAA, and 40 ppb DMAA were 93, 91, and 85%, respectively. The precision (relative standard deviation) of the method obtained in 10 replicate analyses of urine samples spiked with arsenic metabolites varied from 3.2 to 4.6%. This method is applicable to urine samples in studies relating to arsenic exposure and its monitoring. PMID- 8199483 TI - Stability of sulfaquinoxaline, sulfadimethoxine, and their N4-acetyl derivatives in chicken tissues during frozen storage. AB - The N4-acetyl derivatives of sulfaquinoxaline and sulfadimethoxine were stable in fortified chicken liver and thigh muscle tissues during frozen storage for 1 year at -20 and -70 degrees C. In contrast, the parent compounds depleted approximately 35% in liver tissues at -20 degrees C. The transformation of the depleted sulfa drugs to their N4-glucopyranosyl derivatives was negligible, suggesting that products other than glucosides resulted during the storage period. PMID- 8199484 TI - Quantitative detection of whey cream in sweet cream and butter. AB - A simple and sensitive assay is described that can detect trace amounts of whey cream in sweet cream and in butter made from that cream. The method is based on the detection of sialic acid and involves a color reaction between Ehrlich's reagent and sialic acid. The procedure is faster than other methods for detection of whey. The method could be termed semiquantitative because of the seasonal variability of sialic acid in cow's milk. However, with a calibration curve, the method is quantitative and can easily detect as little as 1% whey cream in sweet cream and in the resulting butter. With 1% whey cream in sweet cream, the purple color indicating the presence of sialic acid is visible to the naked eye. PMID- 8199485 TI - Simultaneous screening of fumonisin B1, aflatoxin B1, and zearalenone by line immunoblot: a computer-assisted multianalyte assay system. AB - A line immunoblot assay was developed for the simultaneous screening of fumonisin B1 (FB1), aflatoxin B1 (AFB1), and zearalenone (ZEA). Monoclonal antibodies for each of these toxins were immobilized as multiple lines on nitrocellulose membrane strips and sectored into hydrophobic compartments to minimize use of reagents. A modified enzyme-linked immunosorbent assay was conducted whereby free mycotoxins and horseradish peroxidase-labeled mycotoxins competed for binding to the nitrocellulose-bound antibodies. Color intensity of lines formed by a precipitating substrate was inversely related to mycotoxin concentration. Detection limits for the individual mycotoxins, as determined by visually comparing the color intensity of positive strips to negative controls, were 500, 0.5, and 3 ng/mL for FB1, AB1, and ZEA, respectively. Line density was quantitatively assessed also by using a camera, video monitor, and microcomputer equipped with a video-digitizing board. The assay could be used to determine range values for the various mycotoxins in extracts of spiked corn in less than 30 min, and values could be recorded on the microcomputer hard disk. This combination of line immunoblot assay and image analysis, termed computer-assisted multianalyte assay system, should be applicable to the simultaneous screening of multiple mycotoxins and other agricultural residues in food. PMID- 8199486 TI - An optimized MTT bioassay for determination of cytotoxicity of fumonisins in turkey lymphocytes. AB - In vitro cytotoxicity assays have been performed for detection and quantitation of fumonisins, as possible alternatives for whole animal testing. This study was undertaken to establish optimal in vitro conditions using turkey lymphocytes. Turkey lymphocytes were isolated from peripheral blood by Percoll gradient centrifugation. Cytotoxicity of fumonisin B1 (FB1) and B2 (FB2) was determined by exposing lymphocytes to FB1 or FB2 at concentrations of 0.01-25 micrograms/mL for 24, 48, or 72 h at 39 degrees C. The MTT bioassay was used to measure cell viability and proliferation. In metabolically active cells, the tetrazolium salt, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], was reduced to MTT formazan. Turkey lymphocytes that had been exposed in vitro to FB1 and FB2 for 48 and 72 h showed inhibition of cell proliferation that was dose-dependent. The 50% inhibitory dose for FB1 and FB2 was 0.4-5 micrograms/mL. Cells exposed to FB1 or FB2 exhibited high levels of cytoplasmic vacuolization and were unable to proliferate, whereas proliferation of control lymphocytes was observed at 48 and 72 h. FB2 was 3- to 4-fold more cytotoxic than FB1. PMID- 8199487 TI - Stability and problems in recovery of fumonisins added to corn-based foods. AB - Because the natural occurrence of fumonisins is so far known almost exclusively in corn, we have limited our investigations on their stability to corn-based foods. In these studies, distinction must be made between real losses, binding, and any matrix-related method problems. Fumonisins B1 (FB1) and B2 (FB2) were about 40% recovered when heated in corn meal at 190 degrees C, about 20-30% recovered when heated in moist corn meal at 190 degrees C, and completely unstable in corn meal at 220 degrees C. Average recoveries of FB1 and FB2 added to blank heated matrixes were 69-107% in control experiments. Baking corn meal muffins spiked with 2.5 micrograms FB1 and FB2/g corn meal at 220 degrees C also resulted in losses of fumonisins. Little or no fumonisins were recovered from corn bran flour when methanol-water (3 + 1) was used as extraction solvent. However, when methanol-borate buffer (pH 9.2) (3 + 1) was used, recoveries averaged 91 +/- 17 and 84 +/- 9%, respectively, for FB1 and FB2; and natural contamination of the corn bran flour with FB1 and FB2 at levels of 1.9 and 0.95 microgram/g, respectively, was revealed. Comparable recoveries were observed for 1 brand of a corn bran breakfast cereal, but the binding effect was not seen with a second brand, for which methanol-water (3 + 1) alone was a good extraction solvent. Recoveries of FB1 and FB2 from a mixed cereal for babies were only about 50% with either extraction solvent mixture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199488 TI - Survey of fumonisin production by Fusarium isolated from cereals in Europe. AB - Strains of Fusarium isolated from corn, sorghum, wheat, barley, and mixed feed from Italy, Spain, Poland, and France were tested for the production of fumonisins B1 and B2 (FB1 and FB2) in corn cultures. All strains of F. moniliforme (1 from France, 10 from Italy, 15 from Poland, and 17 from Spain) and the one tested strain of F. proliferatum produced fumonisins in amounts scattered within a wide range of concentrations (0.7-4100 micrograms FB1/g). None or insignificant amounts of FB1 were detected in cultures of 11 F. subglutinans strains (< 0.5 microgram/g for 5 of 11 strains) or in cultures of 3 strains of Fusarium spp. not belonging to Liseola. FB2 was produced by all but one of the strains that produced FB1, and the FB2/FB1 ratio ranged from 0.1 to 0.37 (average, 0.22). The highest production of fumonisin was obtained with isolates from corn (average, 1259 micrograms FB1/g), followed by isolates from wheat (average, 769 micrograms FB1/g) and barley (average, 320 micrograms FB1/g). The production of fumonisins by isolates from sorghum was 2 orders of magnitude lower than corn. These results support data reported for similar surveys in geographical areas other than Europe. In particular, data indicate a situation in Europe that is very similar to North America in respect to fumonisin production by different Fusarium species (F. moniliforme and F. subglutinans) isolated from different substrates (corn and sorghum). PMID- 8199489 TI - [International Consensus on the Diagnosis and Treatment of Bronchial Asthma. Bethesda, Maryland, 1992]. PMID- 8199490 TI - The operation was successful, but the patient died. Reflections on health care costs and social support cuts. PMID- 8199491 TI - Headrests: effective in preventing injuries? PMID- 8199492 TI - Choosing the best inhaler for patients. PMID- 8199493 TI - Can size of spacer make a difference? PMID- 8199494 TI - Spinal manipulation by chiropractors is safe. PMID- 8199495 TI - Family physician's role in diagnosing asthma. PMID- 8199496 TI - Homeopathy. Friend or foe? PMID- 8199497 TI - Radiology rounds. Peptic stricture. PMID- 8199498 TI - Measles recommendations. Consensus conference on measles. Laboratory Centre for Disease Control. PMID- 8199499 TI - Dermacase. Recurrent aphthous stomatitis. PMID- 8199500 TI - Female patients' attitudes to mammography screening. AB - This study compares the attitudes of women who chose or chose not to have mammography screening. Women personally invited by their physicians to have mammography were more likely to go for screening. Those who did not go for screening were more afraid of medical tests and were less likely to want to know whether they had cancer. PMID- 8199501 TI - Self-assessed competence: before and after residency. AB - This study measures changes in clinical confidence experienced by 42 family practice residents as they progressed through a 2-year residency program. At the beginning, 20% or more of respondents reported they lacked confidence in 47 of the 177 topics. Self-assessed competence increased substantially in many areas. However, during the residency, new areas of concern emerged. PMID- 8199502 TI - Pharmacy services in family medicine residencies. Survey of clinics associated with Canadian residency programs. AB - Surveys were mailed to 82 family medicine clinics associated with residency programs in Canada to ascertain the extent, if any, of pharmacy involvement in the programs. Eight of the 58 (13.8%) usable returns had pharmacists directly involved. They provided pharmacy-based services, offered clinical services, and participated in research. PMID- 8199503 TI - Requiring elderly patients to give signed consent for influenza vaccine. Does it affect acceptance? AB - This study aimed to determine whether requiring signed consent before influenza vaccination affected vaccine acceptance by elderly patients. Previous influenza vaccination was determined by chart review. All subjects agreed to sign the consent. Requiring signed consent did not affect influenza vaccine acceptance in this population. Mailed reminder letters and information packages in patients' charts significantly increased vaccination rates. PMID- 8199504 TI - Clinical approaches to low back pain. Part 1. Epidemiology, diagnosis, and prevention. AB - The epidemiology and difficulties in diagnosing low back pain are discussed. Clinical investigations should be limited to those tests that will provide useful information for effective management. Prevention is the best strategy for avoiding low back pain but is realistically hard to practise because the disorder has many environmental and intrinsic risk factors. PMID- 8199506 TI - Health care and seniors. Ethnic, racial, and cultural dimensions. AB - The profiles of Canadian seniors are changing. Racial, cultural, and social context is becoming increasingly important in the health care of seniors. This article discusses the interactions between physicians and seniors affected by ethnocultural variables and suggests a framework for cross-cultural care. PMID- 8199505 TI - Clinical approaches to low back pain. Part 2. Management, sequelae, and disability and compensation. AB - The management and psychologic sequelae of low back pain are discussed. We examine surgery as an option. Questions of disability and compensation, and the physician's role in these processes are examined. PMID- 8199507 TI - Early onset Parkinson's disease. Part 1: The patient's story. AB - Tremors, soreness, and reduced motor control led a 35-year-old woman to her family doctor. The unwelcomed diagnosis was early onset Parkinson's disease. Meeting a family physician with whom she can jointly manage the disease has given this patient courage to face the future. PMID- 8199508 TI - Early onset Parkinson's disease. Part 2: Physician's viewpoint. AB - A young patient with early onset Parkinson's disease helped sharpen her physician's skills in patient education, referrals, hospital-based care, continuing medical education, and assessment of disability. The lessons could be applied to any patient or any disease process. PMID- 8199509 TI - Facial fractures. AB - Emergency room physicians frequently see facial fractures that can have serious consequences for patients if mismanaged. This article reviews the signs, symptoms, imaging techniques, and general modes of treatment of common facial fractures. It focuses on fractures of the mandible, zygomaticomaxillary region, orbital floor, and nose. PMID- 8199510 TI - Chronic cough in children. AB - The two most common causes of chronic cough among children are asthma and recurrent viral upper respiratory infection. Awareness of other potential causes of chronic cough is important. A specific diagnosis can usually be made with a thorough history, physical examination, and simple laboratory investigations. PMID- 8199511 TI - Recurrent abdominal pain during childhood. AB - Recurrent abdominal pain is a common presenting complaint among children. A thorough history and physical examination and limited laboratory investigation should enable a physician to make a positive diagnosis of "functional" recurrent abdominal pain in 90% to 95% of cases; an organic cause is identified in only 5% to 10%. The care and thoroughness of the history and physical examination establish the physician's credibility; explaining the clinical basis for the diagnosis and educating the child and parents on what is known about the condition reassures the parents. PMID- 8199512 TI - Educational contracts in family medicine residency training. AB - An educational contract for family medicine residency training and evaluation addresses many of the difficulties and challenges of current postgraduate medical education. This article identifies important principles for developing a contractual approach; describes the contract used in one program and its implementation; and discusses its theory, advantages, and limitations. PMID- 8199513 TI - Caustic esophageal burns in children. PMID- 8199514 TI - The Annual Scientific Assembly wants you! PMID- 8199515 TI - Threat of litigation. How does it affect family practice? PMID- 8199516 TI - We've come a long way. PMID- 8199517 TI - Advocacy, bias, and the herd instinct in medicine. PMID- 8199518 TI - Radiology rounds. Scleroderma. PMID- 8199519 TI - Dermacase. Trichotillomania. PMID- 8199520 TI - Are physicians meeting the needs of family caregivers of the frail elderly? AB - OBJECTIVE: To explore expressed needs, both formal and informal, of family caregivers of frail elderly. To evaluate roles of physicians. DESIGN: Questionnaire survey of members of the Montreal Jewish community providing care for frail elderly family members. SETTING: Jewish community of Montreal. PARTICIPANTS: Volunteer caregivers who were caring for a family member or friend 60 years or older, who had greatest responsibility for providing physical or emotional support to an elderly person, who saw themselves as caregivers, and who could speak English or French were studied. Of 118 volunteers, 32 were excluded because they withdrew for personal reasons or because they did not meet study criteria. MAIN OUTCOME MEASURES: Demographic variables, functional status of the care receiver, use of home care services, and needs assessment to identify additional services. RESULTS: An average of 75.4% respondents did not use formal support services. Just under half of caregivers were dissatisfied with the attention they received from the health care system, and more than one third expressed feelings of stress, depression, guilt, and isolation. CONCLUSIONS: Hypotheses for this discontent are presented. Physicians may be uninterested in helping caregivers; even if they were receptive to counseling caregivers, they could be poorly remunerated for the types of counseling sessions that are usual for caregivers; and being a professional caregiver to family caregivers is demanding in itself. PMID- 8199521 TI - Attitudes of physicians in northern Ontario to medical malpractice litigation. AB - OBJECTIVE: To survey medical practitioners' experience with and attitudes toward litigation alleging medical malpractice. DESIGN: A survey using a questionnaire. SETTING: The Sudbury and Manitoulin Health District of Northern Ontario. PARTICIPANTS: Medical practitioners in the area. RESULTS: Physicians are sometimes negligent; malpractice is not simply created by entrepreneurial lawyers and patients with unrealistic expectations. At present malpractice is restrained by both the threat of civil litigation and the disciplinary committee of the Ontario College of Physicians and Surgeons. CONCLUSION: We must address the fear of malpractice suits if the North is to attract and retain the physicians it needs to provide modern standards of medical care. PMID- 8199522 TI - [Violence and consumption of illicit drugs in Quebec adolescents. An analysis of their perceptions]. AB - OBJECTIVE: To study adolescents' perception of the connection between violence and the consumption of illegal drugs. DESIGN: A self-administered questionnaire. SETTING: A town with 30,000 inhabitants north of Montreal. PARTICIPANTS: Almost 3300 students between the ages of 12 and 19. RESULTS: About 25% reported that they had been victims of violence by other adolescents who were, in their estimation, under the influence of an illicit drug. This rate increased significantly among adolescents who used drugs themselves, and was highest among female adolescents between the ages of 12 and 15. CONCLUSION: Students, especially young women, who consume illegal drugs are more likely to be victims of violence than those who do not. Family physicians should advise young patients of this risk. PMID- 8199524 TI - Gay patients. Context for care. AB - Gays and lesbians are a part of our society and our practices: real people with real lives, not stereotypes. Understanding their inner world and their social milieu is the first step to providing care that is holistic and appropriate. The "coming out" process and other unique health issues are described. Guidance is provided on how to identify and relate to gay and lesbian patients. PMID- 8199523 TI - High altitude medicine for family physicians. AB - High altitude medicine deals with a continuum of diseases ranging from a mild discomfort to serious ailments affecting all organ systems, including the lungs, brain, and eyes. Decreased oxygen tension is the primary cause. The main principles of prevention are staging and graded ascent to allow acclimatization. Adventure travel to high altitude destinations is becoming increasingly popular; family physicians should be informed of the medical problems associated with such travel. PMID- 8199525 TI - Mineral springs and miracles. AB - Development of hot springs in the Canadian Rockies was closely linked to their reputed medicinal value. In 1885, the federal government created a small reserve around the springs at Sulphur Mountain, an area later enlarged to become Banff National Park, in recognition of the "great sanitary and curative advantage to the public." PMID- 8199526 TI - [HIV and travel. Advice concerning immunizations and pre-travel evaluation]. AB - HIV and AIDS infection has reached epidemic proportions; however, advances in treatment have made it possible for an increasing number of infected individuals to travel. These patients should be given travel advice before they leave. Mainly for political reasons, they should be advised to avoid certain countries. For other destinations, more detailed information might be required. PMID- 8199528 TI - Changing face of physician-patient relationships. PMID- 8199527 TI - Aging and sexuality. AB - Sexual expression among the elderly is a predictor of general health. Considering aging patients' sexual function can affect medical care and improve the quality of their lives. PMID- 8199529 TI - Foreign doctors. Wasted resources? PMID- 8199530 TI - BC's AIDS road show. Evolution of a good idea. PMID- 8199531 TI - Endogenous production of tumor necrosis factor by primary cultures of murine calvarial cells: influence on IL-6 production and osteoclast development. AB - We have previously shown that tumor necrosis factor (TNF) and interleukin-1 (IL 1) acted synergistically to stimulate the production of IL-6 by bone marrow stromal and osteoblastic cells; and that an antibody to IL-6 inhibited TNF induced osteoclast development in murine calvarial cell cultures. Prompted by this evidence, we have now examined whether TNF and/or IL-1 are produced by murine calvarial cells, and whether these cytokines are involved in IL-6 production and osteoclast formation. When cultured under basal conditions, calvarial cells produced TNF and IL-6, and were able to form bone resorbing osteoclasts. A neutralizing antibody against TNF suppressed both basal IL-6 production and the formation of bone resorbing osteoclasts. The anti-TNF antibody also inhibited IL-6 production in response to exogenous IL-1 or parathyroid hormone (PTH). In contrast, a neutralizing anti-IL-1 receptor antibody had no effect on basal, TNF- or PTH-stimulated IL-6 production. These findings suggest that TNF, but not IL-1, is produced by murine bone cells and that endogenous TNF induces the IL-6 production, osteoclast formation, and bone resorption exhibited by these cultures under basal conditions. Furthermore, bone cell-derived TNF amplifies the stimulatory effect of exogenous IL-1 or PTH on IL-6 production by calvarial cells. PMID- 8199532 TI - An association between osteoporosis and premenstrual symptoms and postmenopausal symptoms. AB - This study examined the relationship of premenstrual and postmenopausal symptoms with vertebral osteoporosis by means of a retrospective case control questionnaire in patients with vertebral osteoporosis and control patients. Seventy-five postmenopausal women aged 55-70 years with vertebral osteoporosis and 77 age-matched controls were interviewed at the outpatient clinics of the Royal Hallamshire Hospital, Sheffield, UK to establish the past history of premenstrual symptoms, and present and past history of postmenopausal vasomotor symptoms. The risk of vertebral osteoporosis was significantly greater in women with a history of premenstrual symptoms (RR = 1.86) or oligomenorrhoea (RR = 3.08). Significantly more patients with osteoporosis than controls recalled vasomotor symptoms at the time of the menopause (RR = 1.35). Patients were more likely than controls to describe their symptoms as severe (RR = 1.43) or persistent (RR = 2.19). We conclude that the relative risk of vertebral osteoporosis is increased in women with a history of premenstrual symptoms, irregular periods, and with severe and/or persistent menopausal vasomotor symptoms. PMID- 8199533 TI - The long-term effect of ovariectomy on the quality and quantity of cancellous bone in young macaques. AB - The effect of ovariectomy on the quality and quantity of cancellous bone using the young cynomolgus monkey was evaluated after a 2-year period. The bodies of the second lumbar vertebrae were analyzed for changes in bone mineral quality using density fractionation, chemical analysis, and X-ray diffraction techniques. Changes in bone tissue quality and quantity were evaluated using bone histomorphometry and image analysis. The experimental group (n = 14) was made surgically menopausal (bilaterally ovariectomized), compared with intact controls (n = 16), and then sacrificed after a 2-year period. There was a non-significant shift in the mineralization profile towards less dense bone in the ovariectomized (OVX) vertebrae compared with controls. Physical characteristics of the bone mineral in terms of crystal size or strain were unaffected by OVX. There was a parallel increase in mineral content with fractions of increasing density, however there was no difference in mineral content or the Ca/P ratio in each fraction between treatment groups. Histomorphometric analysis for structural parameters demonstrated no difference in bone volume between control and OVX groups. There was no significant change in trabecular width in the OVX vertebrae compared with controls. There was a significant increase in both osteoid volume and osteoid surface in the OVX vertebrae (P < 0.001). Trabecular architecture as measured by image analysis was unchanged. There was a significant increase in eroded surface in the OVX vertebrae (P < 0.03) compared with the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199534 TI - The role of calcitonin gene-related peptide (CGRP) in macrophages: the presence of functional receptors and effects on proliferation and differentiation into osteoclast-like cells. AB - It has been shown that both calcitonin gene-related peptide (CGRP) and amylin bind weakly to calcitonin (CT) receptors in osteoclast-like cells formed in vitro and inhibit bone resorption by a cAMP-dependent mechanism. Osteoclasts are thought to be derived from cells of the monocyte macrophage lineage, in which CGRP, but not CT, induces cAMP production. In this study, we determined the presence of functional receptors for CGRP in mouse alveolar macrophages and the effects of this peptide on proliferation and osteoclastic differentiation in mouse alveolar and bone marrow-derived macrophages. Human CT did not stimulate cAMP production in macrophages. Human CGRP stimulated cAMP production in mouse alveolar macrophages and bone marrow-derived macrophages dose-dependently. Human amylin, which has 43% homology with human CGRP, also stimulated these macrophages to produce cAMP, but only at a 100-fold higher concentration. The increment in cAMP production induced by human CGRP and amylin was abolished by the addition of human CGRP(8-37), a selective antagonist for CGRP receptors. Specific binding of [125I]human CGRP to alveolar macrophages was detected (dissociation constant, 2.5 x 10(-8) M; binding sites, 1.4 x 10(4)/cell). Amylin, but not CT, displaced the bound [125I]human CGRP from alveolar macrophages, but at a 100-fold higher concentration. No specific binding of [125I]human CT and [125I]human amylin to alveolar macrophages could be detected. Pretreatment with human CGRP for 24 h dose-dependently suppressed DNA synthesis in alveolar macrophages induced by granulocyte-macrophage colony-stimulating factor (GM-CSF). CGRP also suppressed the number of macrophage colonies formed from bone marrow cells induced by macrophage colony-stimulating factor (M-CSF).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199535 TI - Assessment of bone remodeling using biochemical indicators of type I collagen synthesis and degradation: relation to calcium kinetics. AB - In this study, we investigated the relation between calcium kinetic indices of bone remodeling (resorption rate, r; and formation rate, m, respectively) and two serum markers of type I collagen turnover: the pyridinoline cross-linked carboxyterminal telopeptide domains of type I collagen (S-ICTP a marker of bone matrix degradation) and the carboxyterminal propeptide of human type I procollagen (S-PICP, a marker of bone matrix formation). We studied three groups: (i) healthy controls (n = 19), (ii) a mixed group of high and low-turnover bone diseases without mineralization defects (myxedema, thyrotoxicosis and primary hyperparathyroidism n = 38), and (iii) osteoporosis (n = 52). In healthy controls, a significant regression of S-PICP on m was obtained (R = 0.53, SEE/Y = 0.44, P < 0.02). Significant regressions were also demonstrable in high- and low turnover bone disease (R = 0.50, P < 0.001), SEE/Y = 61%) and osteoporosis (R = 0.49, P < 0.001, SEE/Y = 50%). In controls the regression coefficient for the regression of S-ICTP on r was 0.19 (NS), in high and low turnover bone disease 0.66, (SEE/Y = 59%, P < 0.001) and in the osteoporotic group 0.40 (SEE/Y = 61%, P < 0.01). We conclude that S-PICP and S-ICTP reflect whole skeletal bone formation and resorption rates in a variety of metabolic bone diseases including osteoporosis. PMID- 8199536 TI - Familial comparison of bone mineral density at the proximal femur and lumbar spine. AB - Familial resemblance of bone mineral density (BMD) was studied in the lumbar spine and three regions of the proximal femur in 41 biological mother-daughter (M D), 42 mother-son (M-S), 24 mother-grandmother (M-G) pairs and 18 mother grandmother-daughter (M-G-D) triads. Children were placed into three maturity categories based on an assessment of secondary sex characteristics and growth velocities. Two sets of standardized BMD Z-scores were derived for the children based on either their chronological age or their maturational status. These scores were compared with maternal Z-scores derived from age-specific norms. Similar comparisons were made between the Z-scores of the mothers and grandmothers. For all three regions of the proximal femur and for the total AP lumbar spine the correlations between Z-score values were similar and significant (P < 0.05) between the M-G and M-D pairs ranging from 0.41 to 0.57. In general, the familial correlations improved when maturity-status based Z-scores were used for comparison. The absolute BMD values measured in the grandmothers and the three maturity groups of the children--expressed as a percentage of the BMD of the mothers--showed that at the neck and the trochanteric regions of the proximal femur the late-pubescent girls and boys had a significantly (P < 0.05) greater bone density than their mothers (115-123%), whereas at the AP spine these groups averaged only 88% of their mothers BMD. This site differential was not apparent when comparing the post-menopausal grandmothers with the pre-menopausal mothers (80% at both sites). Three generation comparisons demonstrated a strong familial resemblance in bone mineral density. The value of incorporating maturity-based versus chronological-based parameters for comparison with adult measures in studies that involve growing children at different stages of development was also demonstrated. PMID- 8199537 TI - Coping with Serbian repression in an Albanian population. PMID- 8199538 TI - Radiologically guided balloon dilatation of obstructing gastrointestinal strictures. AB - Balloon dilatations is the preferred method of dilatation for most gastrointestinal strictures, because of its efficacy and relative safety. Radiologically guided balloon dilatation was successful in 20 of 24 patients referred for dilatation with a variety of tight gastrointestinal strictures with diameters of 0.5 cm or less. Attempts at endoscopic or bougie dilatation had either failed or were felt unlikely to be successful. A satisfactory result was obtained in all cases in which dilatation was performed. There were no serious complications. Radiologically guided balloon dilatation is both safe and effective for the treatment of very tight or obstructing gastrointestinal strictures. PMID- 8199539 TI - Nasointestinal tube for decompression or enteroclysis: experience with 150 patients. AB - The initial clinical experience with the use of a triple lumen long tube designed for gastrointestinal decompression and enteroclysis is reported in 150 patients. Based on clinical observations, this tube is effective in suctioning retained gastric and intestinal fluid but requires frequent irrigation of the sump port for effective decompression of distended small bowel. In all patients with a preexisting nasogastric tube, the replacement by the decompression/enteroclysis tube was considered more comfortable by the patients. Successful placement of the tube in the jejunum was achieved in 147 of 150 consecutive patients on the initial attempt. The use of this tube obviates dual intubations for decompression and enteroclysis, the attendant discomfort on the patient, and it expedites subsequent performance of enteroclysis if needed. The complications reported with other long intestinal tubes were not observed with this device. PMID- 8199540 TI - Does a normal small-bowel enteroclysis exclude small-bowel disease? A long-term follow-up of consecutive normal studies. AB - The purpose of our study was to determine if a normal small-bowel enteroclysis excludes small-bowel disease in adult patients, using long-term follow-up as the major reference standard. We reviewed 193 consecutive small-bowel enteroclysis (SBE) studies completed during a period from January 1987 to February 1989, of which 83 were judged to be normal at the time of the study. Eight of these latter patients were excluded due to inadequate follow-up. The indications included detection of gastrointestinal bleeding, small-bowel obstruction, Crohn's disease, nonspecific abdominal pain, chronic diarrhea, and a miscellaneous group. Each patient was followed for at least 3 years by chart review or until a definite diagnosis was established. Six of the 75 patients whose SBE was originally interpreted as normal were eventually judged to have small-bowel disease. The remaining 69 patients were judged to be free of small-bowel disease by autopsy, surgical laparotomy, endoscopic observation or biopsy, or long-term follow-up for at least 3 years. Therefore, a normal SBE correctly excluded small-bowel disease in 69 of our 75 patients (true negatives) and failed to diagnose disease in six patients (false negatives), for a specificity of .92 +/- .03 (SE). In this experience, SBE was sufficiently specific in most patients to exclude small-bowel disease. PMID- 8199541 TI - Radiology of the continent ileostomy reservoir: I. Method of examination and normal findings. AB - The aim of the present study is to describe the radiologic methods used to study continent ileostomy reservoirs and to depict the normal radiologic features and variations identified by these procedures. During an 8-year period, 408 double contrast studies were performed in 261 patients. The present study comprises 170 examinations in 99 patients with normal findings. A high-density barium contrast medium and air were used. Modes variation in the size and shape of the reservoirs was observed. The mucosal pattern of the reservoirs resembled that of the ileum but the folds were slightly wider. The continence-providing valves were 3-5 cm long and had a diameter of 2.5-4.0 cm. The diameter of the afferent ileal segments was usually slightly larger than that of more proximal ileal segments, with an upper limit of approximately 4 cm. The efferent ileal segments generally had a straight course without widening or out-pouches. Retrograde barium double contrast examination is a satisfactory method for the evaluation of continent ileostomy reservoirs. Here we define the range of normal variations of such reservoirs as seen on retrograde double-contrast radiologic examinations. PMID- 8199542 TI - Radiology of the continent ileostomy reservoir: II. Findings in patients with late complications. AB - During an 8-year period, 238 barium double-contrast studies performed in 162 patients with continent ileostomy reservoirs who had signs and symptoms of late complications (malfunction of the valve, nonspecific inflammation of the mucosa, stenoses, hernias, and fistulas) showed radiologic abnormalities. The aim of the present study is to depict the radiologic findings in patients with late complications of continent ileostomy reservoirs. With radiologic examination, the correct diagnosis of valve malfunction was made in 96% of patients with surgically proven valve defects. We were able to differentiate between various types of valve dysfunction and complications related to the fixation of the reservoir to the abdominal wall. Inflammatory mucosal changes and fistulas of the reservoir and the afferent ileal segment were depicted with a high degree of accuracy. Barium double-contrast radiologic examination proved to be very valuable in the work-up of patients with dysfunction of continent ileostomy reservoirs. The method was of particular value in assessing the cause of valve dysfunction and in the appraisal of the afferent ileal segment. PMID- 8199544 TI - Pneumatosis cystoides intestinalis: CT findings. AB - Two patients with primary pneumatosis cystoides intestinalis are presented. In both cases, the sigmoid colon was involved and there were no major complications. On computed tomography (CT), at lung window settings, the gas cysts in the colonic wall were clearly delineated. CT was useful in confirming the intramural gas cysts in patients with primary pneumatosis cystoides intestinalis. PMID- 8199543 TI - Colitis in Behcet's disease: characteristics on double-contrast barium enema examination in 20 patients. AB - We performed a retrospective review of double-contrast barium enema examinations of 20 patients with clinically proven Behcet's colitis. Main lesion was ovoid or geographic ulcers with a mean diameter of 2.7 cm. The number of ulcers was single in 15 cases and multiple in five. On six resected specimens, ulcers involved submucosa in three, muscle layer in one, and serosa in two cases with an undermining tendency and transmural inflammation. Aphthous ulcers were present in three cases. Neither perforation nor fistula was demonstrated. In all 20 patients, the ulcer was localized in the ileocecal area, with extension to the ascending colon in seven. Skip lesions were observed in the transverse colon and descending colon in three cases. Destruction of surrounding mucosa resulted in cecal contraction in 19 cases, widening of the ileocecal valve in 19, and fold thickening in the terminal ileum in 12. Six cases (30%) manifested as ileocecal mass accompanied by ulcer, fold thickening, and adjacent mucosal deformity. The appendix was visualized in only three (20%) of the 15 patients with no history of appendectomy. On follow-up study of 15 cases, the ulcers disappeared or decreased in size in 13 cases (86%) and the mucosal deformity was not improved in all cases. On the basis of our results, we believe that the characteristic findings of colitis in Behcet's disease in barium enema examination are ovoid or geographic, relatively large, and deep ulcerations with persistent surrounding deformity which tend to localize in the ileocecal area. PMID- 8199545 TI - Hereditary generalized juvenile polyposis: association with arteriovenous malformations and risk of malignancy. AB - A young man with hereditary juvenile polyposis, a duodenal adenoma with carcinoma in situ, and multiple arteriovenous malformations of the lungs and liver is reported. Because of the risk of malignancy, it is suggested that patients with juvenile polyposis have endoscopic or radiographic surveillance of the upper gastrointestinal tract in addition to either prophylactic colectomy or regular colonoscopic surveillance with polypectomy. In view of the serious potential complications of associated pulmonary, cerebral, and hepatic arteriovenous malformations, screening of patients with juvenile polyposis with chest radiography, magnetic resonance imaging of the brain, and sonography of the liver may be warranted. PMID- 8199546 TI - Laparoscopic cholecystectomy: imaging of complications and normal postoperative CT appearance. AB - Six patients underwent imaging studies to evaluate complications related to laparoscopic cholecystectomy. In addition, computed tomography (CT) of the abdomen and pelvis was performed on six patients 3-5 days after uncomplicated laparoscopic cholecystectomy in order to further clarify the normal postoperative CT appearance in these patients. Complications included ureteral laceration with periureteric hematoma and ureteroperitoneal fistula, hepatic artery pseudoaneurysm, hepatic laceration, retained common bile duct stone, bile leak, and biloma of the abdominal wall. At 3-5 days following uncomplicated laparoscopic cholecystectomy, typical CT findings include fluid density in the gallbladder fossa, a very small amount of pelvic fluid, and small densities within the subcutaneous fat at the expected sites of trocar insertion. PMID- 8199547 TI - Percutaneous transhepatic biliary drainage guided by color Doppler echography. AB - Percutaneous transhepatic biliary drainage (PTBD) guided by color Doppler echography was performed on nine patients. By color Doppler echography, the segmental and subsegmental branches of both the portal vein and the hepatic artery could be identified and discriminated from the bile ducts because of their color flow mapping. We could select the safe pathway of needle advance, which did not injure the vessels. Thus, complication of bleeding did not occur in any of the patients. Color Doppler echography seems a very useful and safe method for the guidance of PTBD. PMID- 8199548 TI - Ciliated hepatic foregut cysts: US, CT, and contrast-enhanced MR imaging. AB - Hepatic foregut cysts are uncommon lesions of the liver. In this report we prospectively examined two patients by means of computed tomography (CT), ultrasound, and contrast-enhanced magnetic resonance imaging. Ciliated hepatic foregut cysts were subsequently demonstrated in both patients following CT-guided biopsy. Magnetic resonance imaging was found to be useful in differentiating these cysts from other lesions. PMID- 8199550 TI - Lymphoepithelial cyst of the pancreas. AB - Lymphoepithelial cyst of the pancreas is a rare lesion which may mimic a pancreatic pseudocyst or mucinous cystic neoplasm. To our knowledge, this lesion has never been reported in the radiologic literature. We present a patient with lymphoepithelial cyst of the pancreas, and we discuss the radiographic and pathologic findings. PMID- 8199549 TI - Macroscopic intrahepatic portal-hepatic venous shunt not associated with chronic hepatic disease. AB - Asymptomatic macroscopic portal-hepatic venous shunt (MPVS) without chronic hepatic disease is a rare vascular lesion. Two cases of this disorder are reported, and the usefulness of color Doppler sonography for studying hemodynamics of such small vascular lesions is stressed. PMID- 8199551 TI - Pancreatic Castleman disease: CT findings. AB - Computed tomography findings in a case of pancreatic localization of Castleman disease are presented correlated with histological findings. This is the second observation in the literature of pancreatic involvement with an unusual histological form. PMID- 8199552 TI - Traumatic pancreatitis in a patient with pancreas divisum: clinical and radiographic features. AB - A previously healthy patient with chronic hyperamylasemia and epigastric pain following blunt abdominal trauma complicated by retroperitoneal hematoma is reported. Endoscopic retrograde cholangiopancreatographic and computerized tomographic examinations revealed pancreatographic characteristics of pancreas divisum with traumatic disruption of the duct of Santorini and adjacent pseudocyst formation. Distal pancreatectomy with cystjejunostomy resulted in total recovery. This represents the first documented case of traumatic pancreatitis in a patient with pancreas divisum. PMID- 8199553 TI - Giant adrenal myelolipomas: CT and MRI findings. AB - The computed tomographic (CT) and magnetic resonance imaging (MRI) features of three giant myelolipomas of the adrenal gland are presented in two patients. CT demonstrates large, fatty retroperitoneal tumors that may be confused with retroperitoneal liposarcoma or very large renal angiomyolipoma. MRI with coronal and sagittal imaging is more sensitive than CT in defining the most likely origin of these tumors as the adrenal gland. PMID- 8199554 TI - MR of the kidneys, liver, and spleen in paroxysmal nocturnal hemoglobinuria. AB - The magnetic resonance (MR) findings in the liver, kidneys, and spleen in eight patients with paroxysmal nocturnal hemoglobinuria (PNH) were retrospectively reviewed to determine whether characteristic features could be demonstrated. Eight patients underwent abdominal MR examinations by gradient echo sequences (seven patients), spin-echo sequences (seven patients), and inversion recovery (one patient). Signal intensities of the kidneys, liver, and spleen were visually evaluated. Autopsy and liver biopsy correlation were available in one case each. Renal signal intensity was decreased in all eight patients by either gradient echo or T2-weighted sequences and in the single inversion recovery sequence. Hepatic signal intensity was decreased in three of eight patients on spin- and gradient-echo images. Splenic signal intensity was decreased in three of eight patients on spin- and gradient-echo images, and in two of these was manifest as focal low signal spots (Gamna-Gandy bodies). While the signal intensity in the renal cortex is typically decreased in patients with PNH, signal intensities in the liver and spleen are variable. Low signal intensity in the kidneys is due to hemosiderin deposition resulting from intravascular hemolysis, whereas low signal intensity in the liver or spleen may be due to either transfusion siderosis, or as a consequence of hepatic or portal venous thrombosis. PMID- 8199555 TI - Needle tract seeding of transitional cell carcinoma following fine-needle aspiration of a renal mass. AB - A 64-year-old man presented with recurrence of transitional cell carcinoma attributed to needle tract seeding of tumor 8 months following fine-needle aspiration of a lower pole renal mass. PMID- 8199556 TI - Rupture of the urinary bladder following cystoscopic clot evacuation: report of two cases diagnosed by CT. AB - Two cases of rupture of the urinary bladder following cystoscopic clot evacuation are presented. Both patients had hemorrhagic cystitis (HC) secondary to cyclophosphamide therapy. The bladder injuries were not immediately recognized. Computed tomography (CT) demonstrated the bladder rupture in both patients. PMID- 8199557 TI - Cystosarcoma phyllodes of the prostate: MRI findings. AB - Cystosarcoma phyllodes of the prostate is a rare, relatively benign sarcoma of the prostate. We describe the magnetic resonance imaging findings in an unusual case of cystosarcoma phyllodes which resulted in extensive local recurrence and sarcomatous degeneration. Although uncommon, radiologists should be aware of the existence of cystosarcoma phyllodes of the prostate. PMID- 8199558 TI - MRI demonstration of peritoneal implants. AB - The magnetic resonance imaging (MRI) findings of 12 proven cases of peritoneal implants, mainly carcinomatosis, were reviewed for evidence of peritoneal seedings. The seeded sites include the pouch of Douglas, the ileocecal and retrocecal regions, the right and left paracolic gutters, Morison's pouch, the right subdiaphragmatic parietal peritoneum, the greater and lesser omentum, the gastrocolic, gastrosplenic, and phrenicocolic ligaments, the small bowel mesentery, the sigmoid and transverse mesocolons, and the small and large bowel walls. Sizes varied from less than 1 cm to omental cake and bulky tumors. The findings include linear or tiny nodular infiltrations of the omentum and subperitoneal fat (ligamentous, mesenteric, and mesocolic), focal or segmental wall thickenings, loss of unilateral colonic haustration with sacculation on the contralateral side, and nodular soft tissue masses along different locations of the peritoneal surfaces. Air was introduced via an antegrade or retrograde method to act as a gastrointestinal contrast agent and was found to be useful for delineating the seedings. As is true with computed tomography scan, miliary implants are also not detectable with MRI. The sensitivity and specificity of MRI in detecting peritoneal implants remain to be determined. PMID- 8199559 TI - Fanconi anemia revisited: old ideas and new advances. AB - This review summarizes both historical and more recent data on the clinical, cellular and genetic features of Fanconi anemia (FA), a rare autosomal recessive disorder. FA patients are characterized by pancytopenia, congenital malformations, growth delay and an increased susceptibility to the development of malignancies, particularly acute myelogenous leukemia. FA cells show chromosomal fragility, slow growth and increased sensitivity to DNA crosslinking agents. FA can be caused by defects in any one of at least four genes. Two general hypotheses have been proposed to explain the underlying defect: loss of a DNA repair function or of a step in the defense toward oxygen toxicity. After many attempts to clone the FA genes, the first one, that defective in group C, has been cloned by complementation of the increased sensitivity of FA(C) cells to mitomycin C and diepoxybutane. This gene (FACC) codes for a novel protein and is ubiquitously expressed. Mutations in various FA(C) patients that cause loss of function have been identified. The review concludes by suggesting directions for future research in FA. PMID- 8199560 TI - Stochastic effects in hemopoiesis. AB - Stochastic effects underlie all hemopoietic cell responses but can only be observed at the level of one or a very few cells. Here we have considered the relevance of stochastic effects to aspects of hemopoietic cell development. PMID- 8199561 TI - Differential sensitivity to cryopreservation of clonogenic progenitor cells and stromal precursors from leukemic and normal bone marrow. AB - The survival of human leukemic and normal progenitor cells was determined after cryopreservation. Thirteen marrows from patients with acute myeloid leukemia (AML) were studied as fresh and eight as cryopreserved samples. Marrows from five normal donors were studied as both fresh and cryopreserved samples. Although the number of bone marrow mononuclear cells (BMMC) recovered after cryopreservation was always lower than that originally stored, no significant difference was observed between the clonogenic potential of fresh and cryopreserved BMMC from either the leukemic or the normal samples. When grown in long-term bone marrow culture (LTBMC), the cultures initiated with cryopreserved BMMC failed to form a confluent stroma, and the duration of nonadherent and progenitor cell production was significantly lower than that from fresh samples. However, when these cryopreserved samples were recharged onto preformed irradiated stroma, the duration of the cultures improved significantly. We conclude that it is the bone marrow stromal cells rather than the clonogenic progenitors which are sensitive to the effects of cryopreservation. Thus cryopreservation does not appear to influence the activity of AML progenitor cells. Our results also indicate that frozen marrow can be used for LTBMC experiments if cultured on a preformed stromal layer. PMID- 8199562 TI - Antileukemic activity of phenylalanine methyl ester (PME): a lysosomotropic peptide methyl ester. AB - The antileukemic activities of the lysosomotropic compounds, such as phenylalanine methyl ester (PME), have received little attention. In this study, a 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to investigate the antileukemic activity of PME. Leukemic specimens from untreated patients that contained greater than or equal to 75% blasts were used. Leukemic cells were treated with PME at 37 degrees C and 22 degrees C in concentrations ranging from 0.5 to 50 mM. Normal blood mononuclear cells served as controls. At both 37 degrees C and 22 degrees C, the recovery of normal peripheral blood cells was approximately 28% following incubation with 50 mM PME. At 37 degrees C, 50 mM PME caused greater than one log reduction of leukemic cells in 13/16 acute myelogenous leukemia (AML), 7/9 acute lymphocytic leukemia (ALL), and 8/8 in blast crisis of chronic myelogenous leukemia (CML-BC) specimens. PME had less activity at 22 degrees C than at 37 degrees C. PME was compared with 100 micrograms/ml 4-hydroperoxycyclophosphamide (4HC). In contrast to PME, 4HC was associated with a greater than one log reduction of leukemic cells in only 1/13 AML, 1/3 ALL and 0/6 CML-BC specimens. 4HC activity exceeded PME activity in only one case each of ALL and prolymphocytic leukemia (PLL). In a case of CD34+ B cell ALL, synergy of PME and 4HC was demonstrated. These studies indicate 1) PME has antileukemic activity and 2) 4HC has less antileukemic activity than PME. PMID- 8199563 TI - T suppressor activated lymphocytes (CD8+/DR+) inhibit megakaryocyte progenitor cell differentiation in a case of acquired amegakaryocytic thrombocytopenic purpura. AB - Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare disease, characterized by isolated thrombocytopenia and the absence of megakaryocytes in bone marrow. Recent studies suggest that this syndrome is due to diverse etiologies. Humoral or cellular mediated suppression has been alternately demonstrated using an in vitro colony assay for megakaryocytic progenitor cells (colony forming units megakaryocyte, [CFU-meg]). We studied a patient affected by AATP, who was not responsive to conventional therapy, but did respond to antilymphocyte globulin. The immunological characterization of marrow lymphocytes showed a marked increase of T activated suppressor cells (CD8+/DR+). Low density bone marrow mononuclear nonadherent cells (MNAC) from the patient, either in aplastic phase or in remission phase, were plated in plasma clot either directly or after T cell depletion (T-dep MNACs). Co-cultures with normal marrow cells were performed using either T lymphocytes from a normal volunteer donor or patient T lymphocytes. In some experiments we added autologous serum instead of fetal calf serum (FCS). In standard conditions, we observed increased colony formation, which was more evident in remission phase and especially significant after T cell depletion. The T lymphocytes from patient marrow did not modify the number of CFU-meg when co-cultured with allogeneic cells. These results indicate that an immune-mediated mechanism could be responsible for this case of AATP, and that the T cell subset CD8+/DR+ is capable of exerting suppression on megakaryocyte differentiation. This suppressive effect seems restricted to patient cells, suggesting a specific auto-sensitization. PMID- 8199564 TI - Leukemia and bone marrow microenvironment. PMID- 8199565 TI - Regulation of hematopoietic progenitor cell migration, mobilization and homing. PMID- 8199566 TI - Graft rejection and second bone marrow transplants for acquired aplastic anaemia: a report from the Aplastic Anaemia Working Party of the European Bone Marrow Transplant Group. AB - Six hundred and eighteen patients with acquired aplastic anaemia grafted from an HLA-identical sibling donor between 1976 and 1990 in eight European centres were reported to the Working Party for Severe Aplastic Anaemia (SAA) Registry and were evaluable for analysis of the incidence of graft failure/rejection and the outcome of second bone marrow transplants (BMT). The number of patients experiencing graft rejection declined significantly over the study period from 32% to 8% (p < 0.0001). This coincided with the introduction of cyclosporine to the conditioning regimen for BMT. The graft rejection rate in the post-hepatitis SAA group was significantly lower than in the group with idiopathic SAA (4% vs 20%) (p = 0.001). The use of irradiation in the conditioning regimen significantly reduced the number of patients experiencing graft rejection (7% vs 21%) (p = 0.004). Age, sex and severity of disease did not influence the rate of sustained engraftment. Of the 85 patients experiencing graft rejection, 41 received a second transplant: their survival is 33% vs 8% for patients not transplanted a second time (p = 0.003). The major factor predicting the outcome of second BMT for SAA was the interval from first BMT. Patients receiving a second BMT within 60 days from the first BMT had a significantly poorer outcome. PMID- 8199567 TI - Allogeneic bone marrow transplantation for acute myeloid leukemia in first complete remission: the effect of FAB classification and GVHD prophylaxis. AB - Ninety-one patients with de novo acute myeloid leukemia (AML) in first complete remission (CR) undergoing an HLA-identical sibling BMT and with a minimum follow up of 12 months were analyzed for disease-related and transplant-related variables predicting survival and relapse. The overall actuarial 5 year survival is 53% and the relapse rate 29%, with a medium follow-up for surviving patients of 1552 days (range 365-4094 days). In univariate analysis the following variables were found to be associated with an increased risk of failure: high dose cyclosporin (CsA), M4-M6 FAB subtype and a long interval (> or = 180 days) between diagnosis and BMT. Other disease-related variables at presentation were not significant, including WBC count > 50 x 10(9)/l, marrow blasts < 70%, time to enter remission > 40 days and > 2 courses to enter remission. Survival was 58% vs 43% for M1-M3 vs M4-M6 FAB subtypes (p = 0.03) and 71% vs 42% for low-dose vs high-dose CsA (p = 0.01). A multivariate analysis was then run separately on survival, relapse and transplant related mortality (TRM). Survival was negatively influenced by M4-M6 FAB subtypes (p = 0.009), high-dose CsA (p = 0.03) and a long interval between diagnosis and BMT (p = 0.04). Leukemia relapse was higher in patients receiving high-dose CsA (p = 0.003) and in females (p = 0.04). Transplant-related mortality was higher in FAB M4-M6 patients (p = 0.01) and patients grafted late after diagnosis (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199568 TI - Clinical and laboratory comparison study of refrigerated and cryopreserved bone marrow for transplantation. AB - Refrigerated storage for short-term preservation of bone marrow is an alternative to cryopreservation where chemotherapeutic regimens include drugs with short in vivo half-lives. We performed a clinical and laboratory comparison of bone marrow stored at 4 degrees C for up to 9 days to bone marrow cryopreserved at -90 degrees C for autotransplantation. After adjusting for the confounding effects of disease type or sex, no clinically meaningful variation in post-transplant course between refrigerated storage and cryopreserved was found. Therefore, the data presented in this study suggest that the clinical recovery indices following transplantation between the two storage groups are essentially equivalent. One potential advantage to refrigerated storage, however, is that it may provide an opportunity for extended exposure to growth factors and/or purging agents in vitro prior to transplantation. To prepare for an in vitro analysis of this hypothesis, we concentrated the stem cell population and compared the nucleated cell recovery, viability and colony forming potential following refrigerated storage of whole bone marrow and buffy coat to cryopreserved bone marrow stored for the same interval. While the nucleated cell recovery for cryopreserved marrow was significantly greater than for refrigerated storage, the viability and colony forming potential of the refrigerated storage was superior or equivalent, independent of prior processing. PMID- 8199569 TI - Successful bone marrow transplantation in patients with previous invasive fungal infections: report of four cases. AB - Patients with previous invasive fungal infections (IFI) are at high risk of reactivation of the infection during BMT, even after an apparently curative antifungal treatment. We report four patients who suffered an IFI after intensive chemotherapy for acute leukemia and were later submitted for BMT. One patient had developed a chronic systemic candidiasis during consolidation chemotherapy and received prophylactic oral or iv fluconazole (200 mg daily) throughout BMT. Two patients developed an invasive pulmonary aspergillosis after intensive chemotherapy, one of them after salvage therapy for post-allogeneic BMT relapse and the other after consolidation therapy. The former patient underwent partial lobectomy after treatment with amphotericin B before a second allogeneic BMT was performed. Both patients received prophylactic itraconazole (400 mg daily by mouth) throughout the BMT procedure. The fourth patient had pneumonia caused by Scedosporium apiospermum (the anamorph form of the fungus Pseudallescheria boydii) during consolidation chemotherapy which was successfully treated with itraconazole. During BMT he also received oral itraconazole (400 mg daily) as prophylaxis against reactivation of the infection. All four patients had successful BMT and none had clinical, radiological or microbiological evidence of reactivation of IFI during BMT. PMID- 8199570 TI - Varicella zoster infection after bone marrow transplantation: incidence, risk factors and complications. AB - The cellular immunoincompetence which follows bone marrow transplantation (BMT) allows both primary and reactivation infection with herpes viruses. We report the overall incidence and timing of varicella zoster virus (VZV) infections after BMT, including the clinical course, complications and associated clinical risk features. Of 1186 patients undergoing BMT through 1989, 216 patients developed VZV infection between 4 days and 10.8 years after BMT; 86% of them within the first 18 months. Of all patients transplanted, 15 +/- 3% by 6 months and 52 +/- 14% by 5 years had developed VZV infection. Dermatomal zoster represented 62% of the infections, while 32% had complicated VZV infection--CNS, disseminated or visceral zoster. All serious infections occurred within 7 months of BMT but only two patients died, both from VZV pneumonitis. Allogeneic and autologous recipients had a similar incidence of VZV infection. VZV seropositive patients had more frequent, earlier and often more complicated or disseminated infections. Age > or = 10 years and radiation in the pre-transplant conditioning were significantly and independently associated with higher rates of VZV infection within a multivariate regression model. Using this model, we could define clinical risk groups with distinctly different hazards of VZV infection: age > 10 years, radiation pre-BMT and VZV seropositive patients had a 44% incidence by 3 years versus age < 10 years, no radiation and VZV seronegative had a 0% incidence by 3 years. Acyclovir assigned for prophylaxis of CMV or HSV infection had no effect on the timing or incidence of VZV infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199571 TI - Prevention of lethal graft-versus-host disease in mice by monoclonal antibodies directed against T cells or their subsets. I. Evidence for the induction of a state of tolerance based on suppression. AB - Lethal GVHD in the fully allogeneic BALB/c (donor)-(C57BL x CBA)F1 (recipient) mouse strain combination could be prevented by a single dose of IgG2b monoclonal antibodies (moAb) directed to T cells. The influence of the time of administration of this moAb after GVHD induction and the effect of anti-T cell subset moAb on the development of GVHD was investigated in this study. Moreover, the state of tolerance in the mice that had become long-term chimeras was examined. Anti-Thy-1 treatment of the recipients 1 day before, 2 h before or 1 day after reconstitution almost completely prevented lethal GVHD. A single dose of 100 micrograms of anti-Thy-1 was as effective as four daily doses of 25 micrograms each. Treatment with a single dose of 25 micrograms or with intervals of 4 days between doses of 25 micrograms was statistically significantly less effective. We injected the recipients with moAb directed to the CD4+ or CD8+ T cells subsets. Using a dose of 100 micrograms moAb, anti-CD4 treatment appeared to be less effective than anti-Thy-1 treatment whereas anti-CD8 treatment was not effective at all. A double dose of anti-CD4 was equally effective as anti-Thy-1 treatment. All mice that became long term survivors remained free of signs of GVHD and were > 99% repopulated with donor type cells. Injection of spleen cells from these BALB/c into (C57BL x CBA)F1 chimeric mice was used to reconstitute lethally irradiated BALB/c, BALB.K and (C57BL x CBA)F1 recipients. Lethal GVHD developed in the BALB.K and (C57BL x CBA)F1 recipients but not in the BALB/c recipients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199572 TI - Recipient-specific donor cytotoxic T lymphocytes enhance engraftment of unrelated, DLA non-identical canine marrow. AB - Resistance to canine marrow grafts from unrelated DLA non-identical donors can be overcome by infusion of viable donor peripheral blood leukocytes or thoracic duct cells in addition to the marrow. The mechanisms by which these cells enhance engraftment are unknown but are likely to include a graft-versus-host reaction. The current study investigated whether recipient-specific, donor alloreactive cytotoxic lymphocytes mediating a graft-versus-host reaction could abrogate resistance to canine marrow grafts. To this purpose, cytotoxic donor lymphocytes (CTL) specific for recipient DLA antigens were generated in vitro and expanded in culture by exogenous interleukin-2 (IL-2). Two groups of dogs were studied. All were given 9.2 Gy total body irradiation followed by 3.7 x 10(8) marrow cells/kg from an unrelated DLA non-identical donor on day 0 and 1.2 x 10(8) host-specific CTL/kg on days 1 and 2. Dogs in group 2 were given, in addition, subcutaneous injections of recombinant human IL-2, 10,000 U/kg twice daily on days 1 through 10 post-grafting. Ten of 16 dogs in the two groups showed hematopoietic engraftment regardless of whether they received in vivo IL-2. Engraftment in current dogs was significantly better than that in 47 controls given marrow alone (p = 0.001), although it was worse than that in 64 dogs given marrow and an order of magnitude higher number of viable mononuclear cells obtained from the peripheral blood (p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199573 TI - Cold agglutinin disease following allogeneic bone marrow transplantation. AB - We describe a case of cold agglutinin disease (CAD) following allogeneic bone marrow transplantation. This 36-year-old male developed CAD 3 weeks after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Cyclosporin A and methotrexate had been administered to prevent graft-versus-host disease. Other agents administered included cytomegalovirus hyperimmune globulin and recombinant human G-CSF. Pericarditis preceded the development of CAD. The characterization of cold agglutinin (CA) was monoclonal IgM-kappa with anti-Pr antigen specificity, probably derived from the engrafted donor lymphocytes. The administration of prednisolone led to transient improvement. The CA titer decreased without further treatment 12 weeks after transplant. PMID- 8199574 TI - Successful unrelated bone marrow transplantation in beta-thalassaemia. AB - A 16-year-old Sardinian girl affected by homozygous beta-thalassaemia was submitted to allogeneic BMT using an HLA-identical, MLC-negative, unrelated donor. The donor and the patient were homozygous for the entire extended haplotype A30, Cw5, B18, F130, DRB1*0301, DRB3*0202, DQA1*0501, DQB1*0201 and heterozygous for DPB1*0301/DPB1*0202. The conditioning regimen consisted of 14 mg/kg busulphan and 160 mg/kg cyclophosphamide. Engraftment was achieved 14 days from BMT and the haematological reconstitution was complete without any signs of acute or chronic GVHD. Seven months after the transplant the patient was in excellent general condition. The hypothesis is advanced that when two HLA extended haplotypes are shared by donors and recipients, particularly in homozygosity, this is a very favourable immunogenetic condition in unrelated BMT. PMID- 8199575 TI - Native valve endocarditis due to Candida parapsilosis: a late complication after bone marrow transplantation-related fungemia. AB - A case of Candida parapsilosis endocarditis observed 16 months after BMT is reported. The patient, a 35-year-old female with CML, suffered from Candida parapsilosis fungemia on day +22 after BMT. In spite of treatment with amphotericin B, fluconazole and catheter withdrawal, the same yeast was isolated > 1 year later from a vegetation on an old rheumatic mitral valve. Although the patient remained in complete cytogenetical and hematological remission, in vitro tests showed reduced phagocytic and chemotactic capacity of neutrophils and monocytes. This case stresses the need of prolonged therapy for patients with candidemia after BMT. PMID- 8199577 TI - Allogeneic bone marrow transplantation for an adolescent with polycythemia vera. AB - Polycythemia vera is a rare clonal disorder of the bone marrow haematopoietic stem cell. We present the case of an adolescent female with polycythemia vera, who was treated with a curative HLA-matched allogeneic bone marrow transplant. PMID- 8199576 TI - Treatment of pure red cell aplasia after major ABO-incompatible bone marrow transplantation resistant to erythropoietin. Bone Marrow Transplantation Team. AB - A case of pure red cell aplasia after major ABO-incompatible bone marrow transplantation with long duration of up to 482 days is presented. The patient exhibited resistance to treatment using intravenous gamma globulin, prednisolone and 8 week administration of erythropoietin. The patient finally responded to treatment using erythropoietin and methylprednisolone simultaneously. Because of its safety and efficacy, it might be worthwhile to try erythropoietin with methylprednisolone, if necessary, for pure red cell aplasia complicating major ABO-incompatible bone marrow transplantation. PMID- 8199578 TI - Guillain-Barre syndrome after autologous bone marrow transplantation for breast cancer: report of two cases. AB - Guillain-Barre syndrome appeared in two patients following autologous bone marrow transplantation for metastatic breast cancer. In one case, the patient responded to plasmapheresis and became ambulatory. In the second case, the patient died of an unrelated complication: intracerebral hemorrhage. Although Guillain-Barre syndrome is associated with hematologic malignancies, it has not been previously reported in patients with solid tumors undergoing autologous bone marrow transplantation. Because both patients were in remission at the time of the autograft, Guillain-Barre syndrome may emerge as a rare complication of altered immune function and/or viral infection after marrow transplantation. PMID- 8199579 TI - Development of infant botulism in a 3-year-old female with neuroblastoma following autologous bone marrow transplantation: potential use of human botulism immune globulin. AB - Infant botulism is a rare disease caused by the release of toxin produced in the intestinal tract by Clostridium botulinum. The disease primarily affects infants under 1 year of age. We report a 3-year-old child with stage IV neuroblastoma who developed symptoms of progressive motor weakness, bulbar palsy and respiratory failure 42 days after autologous BMT. The diagnosis of infant botulism was established by identifying botulism toxin in the stool. Human botulism immune globulin (HBIG) was administered. Following the diagnosis, the patient made significant recovery over the next 7 weeks and was successfully extubated from mechanical ventilation. However, her neuroblastoma eventually recurred and she subsequently died of progressive disease. Although the etiology of the development of infant botulism in this case following autologous BMT still remains unclear, alteration of the intestinal microbial environment from gut sterilization and laminar airflow room isolation or, alternatively, immune suppression during pre- and post-autologous BMT and activation of endogenous spores may have contributed to the development of this disease. The use of HBIG in children with botulism over 1 year of age may be beneficial. PMID- 8199580 TI - Campylobacter jejuni bacteremia and Guillain-Barre syndrome in a patient with GVHD after allogeneic BMT. AB - Guillain-Barre syndrome is a rare neurologic complication after allogeneic BMT. In the non-transplant setting, Guillain-Barre syndrome has typically been associated with antecedent acute infections and numerous reports have suggested an association between Campylobacter jejuni infection and the subsequent development of Guillain-Barre syndrome. Thus far, however, reports of C. jejuni associated Guillain-Barre syndrome have been limited to gastrointestinal C. jejuni infections and none has been reported in BMT transplant patients. We report a case of C. jejuni bacteremia associated with Guillain-Barre syndrome that developed in a patient with chronic GVHD approximately 1 year after allogeneic BMT. The patient was treated with intravenous immunoglobulin and intravenous ciprofloxacin and had partial recovery. Our report illustrates that Guillain-Barre syndrome can occur in association with C. jejuni bacteremia and is a rare cause of polyneuropathy after BMT. PMID- 8199581 TI - Health checks for people aged 75 and over. PMID- 8199582 TI - Shared care of patients with mental health problems. Report of a Joint Royal College Working Group. PMID- 8199583 TI - Definitions of stress. PMID- 8199584 TI - Effective stress management. PMID- 8199585 TI - General practitioners, work and stress. PMID- 8199586 TI - Evaluation of stress management. PMID- 8199587 TI - Coping with stress. The Yateley Stress Group. PMID- 8199589 TI - The application of a general practice database to pharmaco epidemiology. Birmingham Morbidity and Prescribing Information Project. PMID- 8199588 TI - Stress and illness. PMID- 8199590 TI - Portfolio-based learning in general practice. Report of a working group on higher professional education. PMID- 8199591 TI - Insertion of a T next to the donor splice site of intron 1 causes aberrantly spliced mRNA in a case of infantile GM1-gangliosidosis. AB - The lysosomal storage disorders GM1-gangliosidosis and Morquio B syndrome are caused by a complete or partial deficiency of acid beta-galactosidase. Here, we have characterized the mutation segregating in a family with two siblings affected by the severe infantile form of GM1-gangliosidosis. In total mRNA preparations derived from the patients' fibroblasts at least two aberrantly spliced beta-galactosidase transcripts (1 and 2) have been identified. Both transcripts contain a 20 nucleotide (nt) insertion derived from the 5' end of intron 1 of the beta-galactosidase gene. Furthermore, in transcript 2 sequences encoded by exon II are deleted during the splicing process. Comparison of the 20 nt insertion with wild-type intronic sequences indicated that in the genomic DNA of the patients an extra T nucleotide is present immediately downstream of the conserved GT splice donor dinucleotide of intron 1. Both patients are homozygous for the T nucleotide insertion. We propose that this single base insertion is the mutation responsible for aberrant splicing of beta-galactosidase pre-mRNA, giving rise to transcripts that cannot encode a normal protein. PMID- 8199592 TI - Familial adenomatous polyposis (FAP): frequency, penetrance, and mutation rate. AB - The nationwide Danish polyposis register includes all known Danish cases of familial adenomatous polyposis (FAP) and their relatives. By identifying all FAP patients born between 1920 and 1949, we found the frequency of the disease to be 1 in 13,528. By comparing the number of affected and nonaffected offspring born to affected parents during the same period we found the penetrance of the disease for inherited cases to be close to 100% at the age of 40 years. The mutation rate found by the direct method was 9 mutations per million gametes per generation and the proportion of new mutants was estimated to 25%. Fitness for patients between 15 and 29 years was found close to one, while for patients older than 30 the fitness was reduced, but increasing during the three decades (from 0.44 to 0.71) probably because treatment became more widespread and efficient. As we have used the overall fitness in the period, 0.87, to estimate the mutation rate by the indirect method, we found a lower value than by the direct method, namely 5 mutations per million gametes per generation. PMID- 8199593 TI - Exhaustive analysis of the P53 gene coding sequence by denaturing gradient gel electrophoresis: application to the detection of point mutations in acute leukemias. AB - We report the set-up of a denaturant gradient gel electrophoresis (DGGE) assay to screen for mutations in the whole coding sequence of the p53 gene. These DGGE experimental conditions were applied to the analysis of the p53 gene in acute leukemias. Forty adults with acute myelogenous leukemia (AML) and 21 with acute lymphoid leukemia (ALL) were investigated. Eleven of the AML patients were investigated at the time of the initial diagnosis and at relapse. In contrast with most reports based on amplified fragments analyzed by single-strand conformation electrophoresis and focusing on exons 5 to 8, we analyzed the whole coding sequence of the gene. Two of the 40 AML patients displayed a point mutation in exon 7; it was either an A to G substitution that converted Tyr-234 to Cys, or a G to A change that converted Arg-248 to Gln. The screening procedure led to the discovery of several intronic and exonic polymorphisms. These results confirm the low incidence of p53 mutations in acute leukemias and suggest a limited role of the p53 protein in leukemogenesis. The computerized modeling and electrophoresis parameters presented here provide a powerful tool for the exhaustive characterization of p53 mutants in all kinds of malignancies. PMID- 8199594 TI - Identification of a point mutation and germinal mosaicism in a Duchenne muscular dystrophy family. AB - Duchenne and Becker muscular dystrophies (DMD and BMD) are allelic X-linked disorders arising from mutations in the (2.4 Mb) dystrophin gene at Xp21. We have applied the reverse transcriptase-polymerase chain reaction (RT-PCR) to identify a larger than normal dystrophin mRNA from a male with Duchenne muscular dystrophy and his younger affected brother. The increased size of the dystrophin mRNA was due to a splice-site mutation at the exon 26:intron 26 junction where a T to G substitution prevented normal RNA processing. A cryptic splice-site, downstream of the mutation, was activated during processing, resulting in the inclusion of 117 bases of intron 26. This insertion introduced an in-frame stop codon into the mature dystrophin mRNA. An allele-specific test was developed to identify the mutation and was applied to this family. Interestingly, the mother of the two affected boys did not carry the mutation, as determined by allele-specific amplification and direct DNA sequence analysis, indicating gonadal mosaicism. Her eldest daughter, designated as a carrier based upon conventional testing and haplotype analysis, also did not carry the family mutation. Initial haplotyping of the family appeared to be straightforward with gonadal mosaicism becoming evident only after allele-specific analysis. The application of linked markers to identify the disease allele for conventional genetic counselling would have been erroneous in this family and highlights the diagnostic power of precise identification of the disease-causing mutation. PMID- 8199595 TI - Pyruvate dehydrogenase deficiency in a male caused by a point mutation (F205L) in the E1 alpha subunit. PMID- 8199596 TI - A novel mutation (Val-373 to Glu) in the catalytic domain of factor IX, resulting in moderately/severe hemophilia B in a southern French patient. PMID- 8199597 TI - Sequence of the -530 region of the beta-globin gene of sickle cell anemia patients with the Arabian haplotype. PMID- 8199598 TI - Does cancer kill the individual and save the species? AB - I have argued that most germline mutations are due to endogenous process. I speculate that endogenous control of germline mutation serves an important biological function. A certain rate of mutation is required to generate sufficient variation for adaptation during evolutionary time. Sexual reproduction and recombination may serve to enhance variation, but ultimately new germline mutation is required to replenish variant alleles lost secondary to negative selection, genetic drift, and population bottlenecks. Unfortunately, the requisite mutation rates carry a terrible price: for each advantageous mutation, there are many disadvantageous ones. Thus, all mammals are plagued with substantial Mendelian and multifactorial disease. Consequently, the optimal mutation rate should be at a level just sufficient to maintain the requisite variation needed for adaptation. In this view, mechanisms for negative selection are necessary to keep the mutation rate in check. If a high germline mutation rate produces a high mutation rate in somatic tissues, cancer may be an important mediator of negative selection. The multiple mutations necessary to produce cancer serve to amplify relatively small differences in the mutation rate, thereby providing an efficient selection against individuals with germline mutations that result in a high mutation rate. This hypothesis can account for the general similarity of the longevity-corrected cancer incidence profile and the small but significant prevalence of cancer before and during the reproductive period. While this hypothesis must presently be viewed as speculative, it integrates certain previously disjointed observations and suggests an alternative to the general assumption that cancer represents a breakdown in normal physiology. PMID- 8199599 TI - Mutation detection by denaturing gradient gel electrophoresis (DGGE). AB - The molecular analysis of genetic diseases relies on several technical approaches which allow genetic and physical mapping, characterization of the gene structure, expression studies, and identification of disease-causing mutations. Denaturing gradient gel electrophoresis (DGGE) allows the rapid screening for single base changes in enzymatically amplified DNA. The technique is based on the migration of double-stranded DNA molecules through polyacrylamide gels containing linearly increasing concentrations of a denaturing agent. In this review DGGE and the several modifications of the original protocol are presented. Moreover, its applications in human molecular genetics are summarized together with a preliminary comparison with other mutation detection technologies such as chemical cleavage, RNase protection, and single-strand conformation polymorphism. PMID- 8199600 TI - D2 dopamine receptor gene and obesity. AB - The prevalence of Taql A D2 dopamine receptor (DRD2) alleles was determined in 73 obese women and men. In this sample with a mean body mass index of 35.1, the A1 (minor) allele of the DRD2 gene was present in 45.2% of these nonalcohol, nondrug abusing subjects. The DRD2 A1 allele was not associated with a number of cardiovascular risk factors examined, including blood lipids (cholesterol, high density lipoprotein [HDL]- and low-density lipoprotein [LDL]-cholesterol, and triglycerides). However, phenotypic factors characterized by the presence of parental history and postpuberty onset of obesity as well as carbohydrate preference were associated with obese subjects carrying the A1 allele. The cumulative number of these three factors was positively and significantly (p < .0002) related to A1 allelic prevalence. The data showing an association of the minor allele of the DRD2 gene with phenotypic characteristics suggest that this gene, located on q22-q23 region of chromosome 11, confers susceptibility to a subtype of this disorder. PMID- 8199601 TI - Dissociation, childhood trauma, and the response to fluoxetine in bulimic patients. AB - Histories of childhood trauma have been reported previously in bulimic subjects but no study to date has assessed how these experiences may affect response to fluoxetine. Thirty outpatient subjects in a placebo-controlled trial of 60 mg of fluoxetine for the treatment of bulimia nervosa completed the Dissociative Experiences Scale and a self-report instrument assessing trauma. Response to treatment was measured with the Hamilton Depression Scale-17 (HAMD-17), the CGI, the PGI, and the change in number of binges per day. Subjects taking fluoxetine with histories of physical abuse showed a significantly greater drop in HAMD-17 scores than those without such histories. No relationship between a reported history of abuse and the response of binging to fluoxetine was found. A history of abuse does not appear to predict the response of binging to fluoxetine but may predict a greater response of nonspecific symptoms like depression. PMID- 8199602 TI - Sexual abuse histories among treatment-resistant bulimia nervosa patients. AB - Although cognitive behavior therapy has been found to be an effective treatment for bulimia nervosa, it has been noted that a subset of patients fail to engage in treatment. We examined the connection between a history of sexual abuse and symptoms suggestive of poor prognosis including a history of multiple therapists or hospitalizations, self-injury or suicide attempts, and alcohol or drug problems. Subjects were 464 bulimic women in treatment at a residential facility for women with eating disorders. Of the women with all of the indicators of poor prognosis, approximately 71% reported a history of sexual abuse. Of the women who reported none of the symptoms indicative of poor prognosis, only 15% reported a history of abuse, and none of these women reported recurrent abuse (greater than five times). We discuss the possible connections between previous treatment failures and histories of abuse and discuss the implications for successful case formulation and treatment. PMID- 8199603 TI - Five-year outcome from eating disorders: relevance of personality disorders. AB - In order to assess the relationship of personality disorder and eating disorder outcome 30 eating disordered patients were followed up 4-5 years after taking part in a study examining the prevalence of personality disorders in eating disordered individuals. Subjects with personality disorders did not differ from those without personality disorders in the amount of symptomatic change over time, although their psychopathology generally remained more severe. The relationship of personality disorder and clinical outcome ratings varied depending on the personality measure. SCID-II personality disorder diagnoses were not significantly associated with outcome ratings, but were related to a greater likelihood to be hospitalized and treated with psychotropic medications. Results with a new personality measure, the Wisconsin Personality Inventory, did display an association between personality disturbance and eating disorder outcome ratings and also suggested that borderline personality was a significant predictor of outcome. PMID- 8199604 TI - Open trial of fluvoxamine in the treatment of bulimia nervosa. AB - Twenty patients suffering from bulimia nervosa received 50-150 mg fluvoxamine daily for a period of 8 weeks. Primary end-points included the Eating Disorders Inventory (EDI), the Severity Index of Bulimic Condition (BINGE), Clinical Global Impression (CGI) scores, and the number of binge eating episodes per week. Other variables assessed included the 17-item Hamilton Depression Scale and adverse experience checklist. Compared with baseline, total EDI scores increased significantly from 137.8 to 155.3 after 8 weeks of fluvoxamine treatment (p < .001); CGI score fell significantly from 3.5 to 2.3 (p < .01) during this period. The mean number of binge eating episodes recorded by patients significantly decreased (p < .001). Further significant improvements in bulimic behavior were noted using the BINGE questionnaire. Nine of 20 patients complained of adverse experiences, all of which were mild; the most common symptoms were somnolence (n = 4) and insomnia (n = 3). Fluvoxamine appears to be a safe and effective treatment for bulimia nervosa. PMID- 8199605 TI - Controlled trial of zinc supplementation in anorexia nervosa. AB - Zinc supplementation of anorexia nervosa (AN) patients has been reported to increase the weight gain of AN patients in open trials. In this randomized, double-blind, placebo-controlled trial 100 mg of zinc gluconate, or placebo, was given daily to 35 female AN inpatients until they achieved a 10% increase in body mass index (BMI). The rate of increase in BMI of the zinc supplemented group (n = 16) was twice that of the placebo group (n = 19), and this difference was statistically significant (p = .03). The use of zinc supplementation should be considered in the treatment of AN patients. PMID- 8199606 TI - The influence of body fat content and bone diameter measurements on body dissatisfaction in adult women. AB - This study investigated the simultaneous influence of various anthropometric factors on body dissatisfaction in adult women while controlling for psychological and behavioral factors known to covary with it. Multiple regression analyses confirmed that neuroticism, skeletal frame size, and percent body fat were positively, and age and physical activity inversely, related to dissatisfaction. Subsequent analyses substituted separate bone diameter measurements in place of the composite frame size variable and found that hip diameter, correcting for fatness, was a more salient factor in the determination of body dissatisfaction than the more general estimate of frame size. In pursuit of the perfect ultra-slender body women are encouraged to diet and exercise for weight loss more than ever before. It appears, however, that anatomical factors that are resistant to change by caloric restriction or physical activity, are a significant influence in the degree to which women report discontent with their body shape. PMID- 8199607 TI - Eating disorder inventory in the assessment of psychosocial status in the obese patients prior to and at long-term following biliopancreatic diversion for obesity. AB - Psychological traits of obese patients, assessed with the Eating Disorder Inventory (EDI), were compared to those of subjects in the long-term following biliopancreatic diversion for obesity (BPD), when body weight has been steadily normal for over 1 year and any preoccupation with dieting and weight has been completely abandoned. The overall results suggest that the stable body weight normalization on a completely free diet does confer considerable psychological benefit on obese individuals. On the basis of the EDI results, post-BPD subjects were divided into weight-preoccupied and not-weight-preoccupied individuals. In the not-weight-preoccupied subjects, the psychosocial status and emotional rectivity were closely similar to those observed in lean control persons, whereas the few weight-preoccupied subjects, in spite of completely normal body weight, showed residual body dissatisfaction and personality traits very similar to those of eating-disordered patients. PMID- 8199608 TI - Total body nitrogen as a predictor of clinical status in anorexia nervosa. AB - It has been demonstrated that clinical outcome is positively correlated with depletion of total body nitrogen (TBN) and therefore of body protein in certain serious medical conditions such as cystic fibrosis or patients receiving dialysis for chronic renal failure. Patients with anorexia nervosa are not suffering from medical illness per se yet the illness can be chronic and severely debilitating requiring numerous hospitalizations for refeeding and/or management of medical complications. The prediction of chronicity remains an important and difficult issue that this study seeks to address by examining the correlation between several clinical indices in 18 patients suffering from anorexia nervosa with parameters of body composition, namely TBN and percentage body fat. TBN was measured using the technique of in vivo neutron-activation analysis (IVNAA) and expressed as nitrogen index. Percentage body fat was estimated using skinfold measurements. The highest correlation was between nitrogen index and number of hospitalizations (r = -.80). The data support a relationship between depletion of body nitrogen/protein and chronicity in anorexia nervosa. PMID- 8199609 TI - Selective processing of food and body size words: application of the Stroop Test with obese restrained eaters, anorexics, and normals. AB - The specificity of the retardation effect on the Stroop Naming task with eating disorder clients was examined by comparing anorexic patients and normal weight controls with obese restrained eaters. Although the expected differences between normal weight controls and anorexics were found for color naming of food and body size words, obese restrained eaters were not differentiated from the clinical sample. It is suggested, therefore, that the Stroop phenomena do not have a precise relationship to the extent of psychopathology and that factors such as the ability to "fake" the test and poor concentration leading to general slowing, may explain the results. PMID- 8199610 TI - Instability of restraint among clinical binge eaters: a methodological note. AB - The Three Factor Eating Questionnaire was administered to 47 clinical binge eaters at the end of days on which they had and had not binged. Scores on each of the subscales of the questionnaire differed significantly for binge versus nonbinge days. Implications for methodological improvements in future studies are suggested. PMID- 8199611 TI - Impulsivity ratings in bulimia nervosa: relationship to binge eating behaviors. AB - Although impulsive behavioral patterns are often described by patients with bulimia nervosa, there has been little formal evaluation of the relationship between impulsivity and eating-related symptomatology in this disorder. In this controlled outpatient study, ratings on the Barratt Impulsivity Scale were significantly elevated in 20 women with bulimia nervosa in comparison to 20 healthy female volunteers. Frequency of binge eating episodes was not significantly correlated with impulsivity ratings. Although these results indicate increased prevalence of impulsive behavioral style in patients with bulimia nervosa, impulsivity per se does not appear to be a predictor of symptom severity as reflected in frequency of bulimic episodes. PMID- 8199612 TI - Hypercholesterolemia in bulimia nervosa. AB - Patients with bulimia nervosa may present with serum cholesterol levels higher than the recommended range. Giving advice on dietary modification to reduce cholesterol levels runs contrary to the cognitive behavioral strategies used to treat bulimia nervosa. This would not be a problem if it were found that cholesterol levels fell with clinical improvement in the eating disorder. PMID- 8199613 TI - Self-induced abortion in a bulimic woman. AB - We report the case of a woman with bulimia nervosa, several personality disorders, and a past history of anorexia nervosa who deliberately induced an abortion via self-imposed starvation and vigorous exercise. Her history reveals severe obsessive-compulsive and narcissistic personality disorders as well as a lifelong pattern of denial of affect and illness. PMID- 8199614 TI - Anorexia nervosa and tuberculosis: case reports and a review of immune mechanisms. AB - A pair of identical twins living together and with a long-standing history of anorexia nervosa were admitted to restore weight. In the course of their admission one of them was found to be suffering from pulmonary tuberculosis and the other developed tuberculosis after 1 year. We seek to highlight factors that can lead to a delay in case detection and discuss issues relating to the immune mechanisms in tuberculosis and anorexia nervosa. PMID- 8199616 TI - Comparison of the histochemical and contractile properties of human gastrocnemius muscle. PMID- 8199615 TI - Development of clinical standards in industrial rehabilitation. AB - Before discussing adjustments in the fees for the clinical services of industrial rehabilitation, the Medical Free Guide Committee of the Maryland Industrial Commission requested a copy of the clinical standards for these services. However, there were no multidisciplinary standards for industrial services that had state-wide approval. Therefore, a committee was formed to write the standards. Following a review of the literature and unpublished work from other associations and state organizations, standards were developed. Constructive criticism was solicited from national and local professionals and organizations with demonstrated interest and experience in providing or using these services or with experience writing standards. Further comment was solicited from individuals in the state of Maryland before final editing. Because of the dearth of outcome studies supporting the efficacy of clinical services in industrial rehabilitation, the standards describing a level of expectation from clinical services have become important for state organizations responsible for making decisions on reimbursement for clinical services. This paper summarizes the process used for the development of clinical standards of industrial rehabilitation services. PMID- 8199617 TI - A global look at compliance in health/safety and rehabilitation. AB - The problem of compliance with safety and/or treatment programs is enormous. The purpose of this paper is to provide a foundation for development of a more global view of compliance. A literature review on the influence of motivation, attitude formation, and health beliefs and their impact on health behaviors is provided. Traditionally, compliance means that the patient does what the health professional wants. What is needed is for the patient to internalize a program. We must sell programs to the patient! Compliance with programs depends on the person's behavior-change skills and the supports or barriers encountered in the behavior change attempts. Knowing the person's concept of the condition and his power over it, known as the locus of control, is critical. Successful therapists help patients decide to follow a program. Successful sales people know their product, learn the prospect's dominant buying motive, combine facts with benefits, and present arguments that fit the person's belief system and norms. PMID- 8199618 TI - Objective evaluation of functional capacity: medical, occupational, and legal settings. AB - Clinicians are called upon to perform objective evaluation of functional capacity in a variety of treatment and evaluation settings. To assist the clinician in selecting the appropriate testing methods for assessment of functional capacity in different settings, a survey of available techniques is presented. It is structured around the goals of treatment as the patient progresses from the stage of acute injury or disease through early postacute care to long-term rehabilitation. The role of the clinician in treatment of the patient is contrasted to the role of the clinician in evaluation of the patient for reasons other than making clinical decisions. In particular, the specific demands of workers fitness and risk evaluation are described. The goal-related differences in the design and the correct use of clinical dynamometers vs. work simulators are presented. The key concepts are the professional role of the clinician, reliability of measurements, and validity in the sense of the decisions one is justified in making based on the results of these measurements in a particular context. PMID- 8199619 TI - The United States Army physical therapy experience: evaluation and treatment of patients with neuromusculoskeletal disorders. AB - Army physical therapists have had unique experiences relevant to orthopaedic physical therapy. The educational process, expanded clinical privileges, and physician supervisor role as developed to prepare and support physical therapists working as primary neuromusculoskeletal screeners are summarized. After-action reports demonstrate that Army physical therapists can evaluate and treat one third of all sick-call patients generated in field training missions and significantly improve return-to-duty rates without requiring physician intervention. The historic events that led to the physician-extender role in the evaluation and treatment of patients with neuromusculoskeletal conditions are presented. These events support the current battlefield assignment of physical therapists as far forward as the inflatable Combat Support Hospitals. The scope of Army physical therapy practice continues to evolve and expand to meet the new challenge of nation assistance, peace-keeping, and humanitarian missions. PMID- 8199620 TI - Active surveillance for the control of cumulative trauma disorders: a working model in the newspaper industry. AB - Health and risk factor surveillance is a critical aspect of an effective ergonomics process. Physical therapists are becoming increasingly involved in many components of the ergonomics process, including health and risk factor surveillance. The purpose of this study was to develop and implement a multistaged active surveillance program for the management and control of cumulative trauma disorders. The surveillance program was established at three newspaper companies consisting of 1,150 employees. This study focused on the first three stages of the multistage surveillance model, which incorporates the use of symptom and job factor questionnaires, specific anatomical surveys, and clinical detection tests. The results of the study indicated that 1) musculoskeletal symptoms in the back, neck, and hands accounted for the majority of reported missed work among the newspaper workers; 2) production workers had a higher prevalence of musculoskeletal symptoms than office workers; and 3) the prevalence of probable carpal tunnel syndrome among the newspaper workers was 1.5%. PMID- 8199621 TI - Therapists' ability to identify safe maximum lifting in low back pain patients during functional capacity evaluation. AB - Functional capacity evaluation (FCE) of an injured worker's ability to lift weight guides the determination of whether he or she is capable of handling the physical demands of a job. The purpose of this study was to examine the interrater and intrarater reliability in determining the safe maximum floor-to waist lift for patients with low back pain during FCE testing. Twenty-one patients with low back pain were evaluated. Patients were videotaped lifting weight in progressive increments using a kinesiophysical approach. Five experienced physical therapists viewed the videotape and judged the lifts for body mechanics safety. Safety reliability was high, indicating that therapists can accurately judge safe lifting methods during FCE. As lifting loads increased, body mechanics deteriorated, indicating the patient was approaching or had reached a biomechanical end point. Clinical information is needed, in addition to visual observations, to accurately determine when maximum lift capacity is reached. PMID- 8199622 TI - Injury and proprioception in the lower back. AB - No known research has attempted to quantify proprioception of the lower back or to examine the relationship between injury and proprioception in this region. The primary purpose of this study was to explore relationships between low back injury and proprioception of the lower back. Subjects were 88 working male firefighters from public emergency medical service departments. Three types of lower back proprioception (passive motion threshold, directional motion perception, and repositioning accuracy) were tested. Each type of proprioception was examined in the three primary planes of motion using a device designed by the author. Some anthropometric and personal variables were statistically controlled. All variables underwent multiple correlation analysis. The primary findings were: 1) longevity factors [age (r = .30, p < .01) and years of experience (r = .35, p < .001)] were best correlated with proprioceptive deficits in the sagittal plane; 2) injuries were correlated (p < .05) with proprioceptive deficits in the coronal (r = .22) and sagittal planes (r = .17) and with deficits in multiple planes (r = .19); 3) proprioceptive asymmetries were associated with injuries; and 4) the factor most highly correlated with the history of low back injuries was the presence of a spinal disorder (r = .40, p < .001). Impaired proprioception resulting from injury may degrade lumbar motor function, increasing workers' risk of reinjury. Restoring proprioception of the lumbar spine after injury should be a goal of treatment. PMID- 8199623 TI - An electromyographic analysis of the hip abductors during load carriage: implications for hip joint protection. AB - Decreasing the relative force demands on the hip abductor muscles may reduce hip joint forces. The purpose of this study was to use surface electromyography (EMG) to determine the relative demand on the hip abductor muscles as subjects walked and carried single hand-held loads of multiple weights. Thirty healthy, college aged subjects carried single hand-held loads by their side. The loads weighed between 3 and 30% of body weight. Loads were carried in a position either ipsilateral or contralateral to a given hip side. Normalized EMG (%EMG) was collected during the middle stance phase of walking. The amount of %EMG remained statistically equal to or less than the no-load EMG baseline for all ipsilateral held loads and greater than the no-load EMG for all contralateral-held loads above 3% body weight. Load positions and weights that generated %EMG levels less than or equal to the no-load baseline most likely offer a degree of hip joint protection for persons with hip disability. PMID- 8199624 TI - Nonclinical competencies: a survey of occupational health physical therapists. AB - Consulting with business and industry represents a very new world for physical therapists--a world in which most have had little formal academic preparation. Some competencies in consulting in occupational health physical therapy are beyond specific clinical skills and knowledge. The purpose of this research was to survey occupational health physical therapists (OHPTs) concerning a previously identified list of nonclinical competencies in consulting with business and industry. The survey addressed how OHPTs rated the importance of these competencies, how they rated their own level of competence for each, and how they developed these competencies. The survey sample was based on members of the American Physical Therapy Association Orthopaedic Section's Special Interest Group in Occupational Health Physical Therapy. The response rate was 98% (61/62). Mean importance of competencies was 3.66/4.00 (range 3.00-3.88), which further validated the list of nonclinical competencies. The mean level of competence was 3.17/4.00 (range 2.40-3.50). The mean importance of individual competencies was consistently higher than level of competence. This discrepancy is of practical significance in terms of professional development of OHPTs consulting with business and industry. Primary sources of competence were practical experience (59.87%) and continuing education for physical therapists (15.51%). These results may indicate that current continuing education programs are not meeting OHPTs' educational needs and may serve as a basis for developing programs to better meet these needs. The survey instrument may help OHPTs identify and prioritize their own educational needs and to plan their own professional development accordingly. PMID- 8199625 TI - [Biomedical research: to know the judicial and legal aspects]. AB - In France, therapeutic trials are governed by the so-called Huriet Law of December 20, 1988 concerning the "protection of subjects participating in biomedical research". Urologists must be familiar with this Law to preserve their responsibility. We must make sure that the Sponsor fulfils his obligations and that the information which we give to our patients guarantees the validity of their consent. The authors recall the legal penalties associated with failure to comply with this law. PMID- 8199626 TI - [The results of a 1993 AFU survey on laparoscopy in urology]. AB - The development of laparoscopy in the field of urology has been considerable since 1991. In order to evaluate the use of this technique in the French urology community and the need to develop evaluating and teaching structures for this technique, a postal questionnaire was sent to 714 members of the Association Francaise d'Urologie (AFU) on June 23, 1993. The reply rate was 22% and 72 of the responders (46%) performed urological laparoscopy. A total of 684 laparoscopic urological procedures were reported, corresponding to an average of 9.5 procedures per operator. 45 operators had performed fewer than 16 laparoscopic procedures. The complication rate was 5% with a perioperative mortality of 0.3%. These figures should be considered to be minimal values. Eighty six responders (54%) did not perform laparoscopy. Forty seven of them (57%) were waiting for these techniques to demonstrate their practical value. Eighty two urologists thought that laparoscopic lymph node dissection had a role to play in the diagnostic and therapeutic strategy of prostatic cancer. One hundred and thirteen urologists (85%) considered that the development of urological laparoscopy would be moderate. Eighty nine urologists answer the question concerning possible training in these techniques and 77 of them intended to learn laparoscopic techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199627 TI - [Kidney tumors in Africa. Incidence and anatomo-clinical aspects. Apropos of 123 observed cases at the Central Hospital and at the University Hospital Center in Cameroon]. AB - 123 renal tumours, among which 4 benign, were observed in 13 years. Renal tumours have a low incidence in Africa and are mostly seen in young patients. Nephroblastoma is the most frequent of these tumours. The clinical and paraclinical aspects of these tumours have nothing particular but the diagnosis is usually late. PMID- 8199628 TI - [The contribution of endoscopy in the diagnosis of unilateral hematuria of renal origin and pseudotumors of the upper urinary tract]. AB - From 1985 to 1992, 9 patients (6 males, 3 females) with a mean age of 47 years, presenting with a clinical picture suggestive of a tumour of the upper urinary tract (haematuria and/or pelvic or caliceal radiolucent filling defect), underwent retrograde (6 cases) and/or percutaneous (9 cases) endoscopic exploration of the upper urinary tract. The percutaneous examination allowed a precise diagnosis and appropriate treatment adapted to the lesion detected (papillary necrosis: 2 cases; ectopic papilla: 2 cases; hypertrophy of Brunn's nests: 1 case; papillary angioma: 1 case; haemorrhagic papillitis: 3 cases) in every case. Endoscopic exploration of radiolucent lesions of the upper tract and unexplained renal haematuria is therefore justified whenever the diagnosis of upper tract tumour is uncertain on the basis of the radiological and cytological assessment. PMID- 8199629 TI - [Morbidity of radical prostatectomy for localized cancer of the prostate]. AB - The author reports the morbidity of 173 personal radical prostatectomy operations performed by the same surgeon between 1st June 1985 and 31st December 1992. The early morbidity was negligible. The late morbidity was marked by a single case of complete incontinence (0.5%). Sexual function deteriorated in proportion to the increasing quality of operative haemostasis. PMID- 8199630 TI - [Piezo-electric extracorporeal lithotripsy of non-coralliform kidney calculi with a maximal measurement of greater than or equal to 25 mm. Apropos of 25 cases]. AB - From June 1991 to April 1993, 25 non-staghorn renal stones with a maximal diameter greater than or equal to 25 mm were treated by piezoelectric extracorporeal lithotripsy (EDAP LT 01). The complete success rate was 56% after 1 (16%), 2 (12%), 3 (16%) or 4 sessions (12%). 14 double J ureteric stents were implanted (56% of cases) and 4 complications were observed (2 cases of acute pyelonephritis and 2 cases of ureteric silting). These results were inferior to those obtained with percutaneous surgery, but help to define the potential indications of extracorporeal shock-wave lithotripsy. This treatment modality can therefore be applied to large friable weddellite or even struvite stones, particularly when the anatomical conditions are unfavourable for percutaneous surgery. PMID- 8199631 TI - [Free appendix mucosa urethroplasty. A preliminary experimental study of free grafts of digestive tract mucosa]. AB - The various tissues used as free grafts in urethroplasties are associated with a high incidence of fistulae and strictures. The search for a new, more effective substitute has led the authors to study the possibility of using a new type of mucosa: appendicular mucosa. The size and cylindrical structure of the appendix and its easy resection make it an original and adapted urethral substitute. As most animals do not possess an appendix, an animal model of subcutaneous free graft of colonic mucosa was studied. Segmental transverse colonectomy was performed in 16 rats. The mucosa was stripped and then grafted subcutaneously. Three to six weeks after the operation, this mucosa was still perfectly viable in 11 rats. Its fixation ensures a better take of the graft. Histological examination revealed that the epithelium retained the features of gastrointestinal mucosa: monostratified, pavement and secretory. The results of this preliminary study are very encouraging and justify continuation of experimental studies of free appendicular mucosal urethroplasties. A practical application is expected in the correction of severe hypospadias or extensive urethral strictures. PMID- 8199632 TI - [A technical device for the percutaneous extraction in monobloc of various renal calculi larger than 10 mm]. AB - The authors present a technical device consisting of a modification of the operating channel for stone extraction by percutaneous nephrostomy. For selected stones, widening of the lips of the operating channel allows the stone to be rapidly and entirely removed without the need for ultrasound or hydroelectric fragmentation, which is always associated with a risk of leaving residual fragments. The aim of this technical device is to ensure complete absence of residual fragments with a minimum of risks for the renal parenchyma. PMID- 8199633 TI - [Renal nephrogenic nephroma: an little known exceptional tumor. Apropos of a case disclosed by xanthogranulomatous pyelonephritis]. AB - The authors report a new case of an exceptional benign renal tumour: nephronogenic nephroma, composed of differentiation of the blastema into primitive nephronic formations. It raises the problem of differential diagnosis with adult Wilms' tumour and renal blastematosis. In this patient, it was associated with segmental xanthogranulomatous pyelonephritis, presenting in the form of psoitis and an abscess of the thigh. Total nephrectomy was performed. PMID- 8199634 TI - [A giant cyst of the seminal vesicle associated with ipsilateral uretero-renal agenesis]. AB - The authors present a case of seminal vesicle cyst and discuss the polymorphic clinical features and the examinations required to establish the diagnosis. Treatment is surgical and reserved to cysts with severe symptoms. PMID- 8199636 TI - Benefits of different routes of administration. AB - The benefits of hormone replacement therapy (HRT) are well established for the different systemic administration routes used today. Relief from somatic and vasomotor postmenopausal symptoms can be obtained by all recognized forms of HRT. The prophylactic action of peroral and percutaneous administration of HRT on postmenopausal bone loss is identical if the appropriate protective dosage of the estrogen component is chosen for each galenic form. The second metabolic benefit of HRT, the cardioprotective effect of ERT, is well accepted for the peroral route. New data on the direct effect of estradiol on the arterial wall as well as recent serum lipid results obtained during percutaneous administration of estradiol in postmenopausal women allow the conclusion that the percutaneous route induces cardioprotection similar to that obtained with the classical peroral route. This opinion is supported by animal data. Furthermore, observations in animals suggest that the benefits of ERT are not neutralized by either sequential or fixed addition of progestin to the estrogen. Except in some rare cases with a particular indication for either the peroral or the percutaneous administration of HRT, the choice of route of administration should be made on the basis of maximum acceptability by the patient. PMID- 8199635 TI - [A retrocaval ureter associated with contralateral pelvic renal ectopia.: use of a 3-dimensional scanner. Apropos of a case and review of the literature]. AB - Retrocaval ureter is a rare malformation occasionally associated with other urological or nonurological abnormalities. We report an exceptional case of retrocaval ureter associated with contralateral pelvic ectopic kidney in a 22 year old man. The anomalies associated with the retrocaval ureter and the embryological mechanisms are described. Abdominal computed tomography with 3D reconstruction provided a new perspective of this malformation, but its clinical value remains unclear. PMID- 8199637 TI - Cardioprotection by estrogens: implications of observational studies. AB - Women younger than 50 have a lower age-specific incidence of CVD than men. With advancing age this difference gradually disappears. These well-established facts provide the rationale for numerous primary and a few secondary intervention studies with ERT. With increasing sophistication and longer observation periods, both case-control and cohort studies agree on a cardioprotective effect by estrogens. A meta-analysis suggests that estrogens halve the risk of myocardial infarction (MI). As observational studies do not control exposure, confounders and biases may be present. Even when considering the most pessimistic scenario, however, the clinical significance for preventing MI by ERT would still be substantial; albeit insufficient data from a clinical trial agree on a markedly reduced risk for MI. Some of the primary prevention trials are large enough to permit analysis of subgroups. In women carrying risk factors for CVD, the cardioprotective effect appears to be augmented. Such risk factors comprise smoking, hypertension, and perturbed serum lipids. In women who have already had MI, the relative risk may be as low as 0.2 for those treated with ERT. While there are compelling epidemiologic data to suggest cardioprotection by ERT, the epidemiology on combined therapy and CVD is scanty. However, there is no epidemiological evidence to suggest a reduced cardioprotection by progestogen co medication, but further data are urgently needed in support of this notion. PMID- 8199638 TI - Atherosclerosis and estrogen replacement therapy. AB - Cardiovascular morbidity and mortality increase after menopause. There has been reluctance to use estrogen replacement therapy (ERT) for treating women with a high risk of cardiovascular disease because of adverse experience in two areas: (1) The Coronary Drug Project administered high doses of estrogen to male survivors of MI, which was associated with excess coronary and thromboembolic events. (2) Studies of OC use revealed an increased incidence of heart attacks among women over the age of 35 years who smoke. Eight case-control studies have examined the effect of estrogen replacement therapy on cardiovascular events; five have shown a protective effect. Eleven of 19 reports have found a protective effect. Ten of 11 cohort studies have found a protective effect. One randomized study (by Nachtigall et al) found a beneficial effect. Angiographic studies at the University of Tennessee/Baptist Memorial Hospital, Memphis have examined the relative risk for coronary artery disease for postmenopausal women relative to estrogen use. Cases with significant coronary angiograms. Logistic regression analysis showed that estrogen use had a statistically significant independent protective effect against coronary atherosclerosis. These observations have been confirmed by three subsequent studies. The same study group also examined the effect of estrogen replacement on survival of patients who underwent coronary arteriography at baseline. Of 23,190 patients undergoing arteriography, 2,268 women were eligible for long-term study. While patients who were initially free of coronary artery lesions did not have a significant reduction of mortality when given estrogen replacement, a significant reduction of all-cause mortality was observed in those groups with coronary artery disease who received estrogens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199639 TI - Cardiovascular protection by estrogen: a hemodynamic mechanism? AB - Cardiovascular risk is higher in men than in women, and also more prevalent in postmenopausal than in premenopausal women, especially if not treated by estrogens. These differences may be due, in part, to a cardioprotective action of sex hormones, mainly estrogens. However, only a limited part of this protection may be attributed to metabolic modifications induced by replacement therapy with estrogen. Therefore, it remains to be determined which other cardioprotective mechanisms influenced by sex steroids might be involved. It has been demonstrated that the menopause is associated with an increase in uterine arterial pulsatility index, reflecting increased peripheral resistance, while the administration of estrogens has an opposite effect at this level. In Doppler studies, estrogen replacement therapy was also associated with an increase in stroke volume and flow acceleration in the aorta. This suggests a positive inotropic effect of estrogens. Using technetium scanning, it was found that women at an early phase of menopause have a stronger myocardial contractility than women of a similar age whose menopause is of longer duration. These effects of estrogens on hemodynamic characteristics might be controlled by vasoregulatory hormones such as endothelin(s) or endothelial-derived relaxing factor (EDRF), now identified as nitric oxide (NO). Indeed, sex-associated differences in endothelin have been observed. Such are some of the mechanisms by which estrogen administration might effect a cardiovascular protection. At the present time, however, conclusive data are not available. PMID- 8199640 TI - Cardioprotection by estrogens: mechanisms of action--the lipids. AB - Reductions of total and LDL-cholesterol and, to a lesser extent, increase in HDL are known to decrease cardiovascular disease (CVD) incidence. All oral estrogens are known to induce such changes in a dose-dependent manner at doses commonly used in ERT, somewhat more markedly for estradiol than for conjugated equine estrogens (CEE). Low-dose estriol used for urogenital discomfort is void of lipid effect. Transdermal estradiol induces similar reductions in the important LDL fraction, whereas HDL is less affected. Modified, especially oxidized, LDL is particularly atherogenic. Accumulating evidence suggests estrogen inhibits LDL oxidation in a process not counteracted by progestins. Elevated triglycerides are considered an important risk factor in women aged about 50. Oral estradiol and, especially, conjugated estrogens augment serum triglycerides, whereas estrogens with non-oral delivery systems rather reduce triglyceride concentrations. The clinical significance of pharmacologically induced changes in triglycerides remains to be clarified. Estrogen-induced changes in the serum lipid profile, however, account for no more than a third of the cardioprotective effect. Lipoprotein (a), another important indicator of CVD risk, is probably also reduced by the action of estrogens. Neither lipoprotein (a) nor oxidized LDL is measured by the routine serum lipid profile. At this time it is impossible to deduce the quantitative importance of changes in these two variables with respect to cardioprotection by estrogens. PMID- 8199641 TI - HRT mechanisms of action: carbohydrates. AB - Elevated insulin concentrations are frequently found in both men and women with coronary heart disease (CHD), and are likely to be due to insulin resistance. Hyperinsulinaemia may increase CHD risk by directly promoting atherogenesis, and insulin propeptides may also be important in this respect. However, increased insulin concentrations may adversely affect several other CHD risk factors, and it has been postulated that insulin resistance is a pivotal metabolic disturbance in a constellation of CHD risk factors. There is an association between hyperinsulinaemia and hypertension, although it is not known if this association is direct. Increased insulin concentrations are also associated with high triglycerides, low HDL or HDL2 concentrations, and increased small dense LDL. Obesity is also associated with insulin resistance, and it is the central or android body fat distribution which correlates with these metabolic disturbances. All these associated factors constitute a distinct syndrome--the insulin resistance syndrome--which is a frequent finding in patients with CHD, including microvascular angina. It is possible that the adverse associations of insulin resistance and dyslipidaemia are mediated through increased nonesterified fatty acid flux. Increased insulin levels are also associated with increases in the anti-fibrinolytic factor, plasminogen activator inhibitor-I (PAI-I). Whilst increased insulin levels are typically associated with insulin resistance, reduced hepatic insulin uptake may also be important. We now have techniques which can quantitate insulin secretion, hepatic uptake and release, elimination, and resistance. The menopause has appreciable effect on insulin and glucose metabolism. Estrogen and progesterone augment pancreatic insulin secretion, but the former reduces insulin resistance whilst the latter increases it.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199642 TI - [Obstetrical complications of maternal overweight]. AB - Overweight is associated with a higher risk of cardiovascular and metabolic disease. Pregnancy in obese women frequently results in an increased incidence of maternal complications (gestational diabetes, hypertension, toxemia) and adverse perinatal outcome (macrosomia, perinatal mortality). Cesarean deliveries are also more frequent in obese women, mainly because of cephalopelvic dysproportion due to macrosomia. Optimal treatment for gestational diabetes is difficult to achieve, although hyperglycemia further impairs maternofoetal prognosis. The incidence of intrauterine growth retardation is not increased in obese pregnancy. A successful obstetrical outcome may be achievable through multidisciplinary antenatal management. PMID- 8199643 TI - [Abortion on demand. Descriptive and quantitative study of psychological and psychosocial aspects]. AB - A pilot study investigated 66 women (mean age: 27 years) before or after abortion with a standardised questionnaire in a center for family planning in Bobigny, a northern suburb of Paris. The results were compared to a former study about spontaneous abortion (n = 156) in Regensburg (Germany). More than half of the women were from the oversea departments, Africa and Northern Africa. 30% were foreigners and 75% unmarried. 48% had repetitive abortions. However gynaecological and obstetrical complications were low. The undesired pregnancies were in link with discontinued contraceptive protection of the two partners and low male participation. After the abortion feelings of release and short perturbations were predominant and depressive reactions significantly less frequent than after spontaneous abortion. Serious disorders were rare. PMID- 8199644 TI - [Predictors of sexual behavior in a group of heterosexual university students at risk for AIDS in Montreal]. AB - In order to evaluate the predictors of risky sexual behavior and AIDS, 573 male and female college students enrolled in French speaking universities in Montreal answered a questionnaire dealing with their sexual behaviors, from which an index of risks was computed (CASH). The analyses show that the best predictors of the CASH for men are associated to their sexual partner taking the pill, peer attitudes toward sexuality and individual sensation-seeking index. For women the best predictors of risky sexual behaviors are the perception of chances to catch AIDS, use of drugs or alcohol during coital behavior, peer group attitudes, personal sexual attitudes and using the pill as a contraceptive. These results suggest that risky sexual behaviors depend on complex processes associated to lifestyle and personality structures. PMID- 8199645 TI - [Menopause: can a new myth replace an old one?]. AB - The menopause was considered in the past as a critical age during which women who no more can procreate stop being a real female. Actually it is estimated as a situation of hormonal deficiency which should be heated with the well-known. But limitation of this period to exclusive hormonal went seems reducing. At the menopause women have to manage the bereaving a part of their peculiar identity, the real and imaginary fertility. That needs a mental reorganization which may be difficult to be faced and may be in origin of neurosis and various somatic events. Therapeutics are now able to approach this period in comfortable conditions as well on the somatic than the functional level. But it is undeniable that during the consultation something else than only the hormonal aspects of the woman's story is getting in stage. PMID- 8199646 TI - [Current value of endometrial biopsy]. PMID- 8199647 TI - [Preimplantation genetic diagnosis. From research to clinical application]. PMID- 8199648 TI - [Metrorrhagia caused by estrogen-progestin combinations]. PMID- 8199649 TI - [History, technique, and results of puncture biopsies of para-uterine cysts]. PMID- 8199650 TI - Nimodipine after circulatory arrest: effects on oxygen delivery and consumption. AB - PURPOSE: Evaluation of the effects of nimodipine administration during and after cardiopulmonary resuscitation (CPR) on oxygen delivery and consumption was the aim of this study. METHODS: A randomized double-blind study in 32 anesthetized domestic pigs was performed. After 5 minutes of ventricular fibrillation (VF) and 5 minutes of external CPR, epinephrine (50 micrograms/kg) and either nimodipine or placebo (10 micrograms/kg bolus, 1 microgram/kg/min continuously throughout 4 hours of observation) were administered. One minute later (equal to 11 minutes VF), the first countershock was given. If this failed to restore spontaneous circulation, epinephrine and countershocks were repeated for a maximum of 30 minutes. RESULTS: Eleven of 12 nimodipine- and 7 of 14 placebo-treated pigs could be resuscitated successfully and survived the observation period (P < .05). Hemodynamic responses to nimodipine were characterized by significant decreases in systemic vascular resistance and mean arterial pressure from 10 minutes after restoration of spontaneous circulation onwards with consequent significant increases in cardiac output. Median systemic oxygen delivery indices (DO2I) in nimodipine-treated pigs were significantly higher at all measuring points when compared with placebo-treated animals. Median systemic oxygen consumption indices (VO2I) did not differ significantly between groups. Median oxygen extraction ratios in nimodipine-treated pigs were in the same range as prearrest and were lower when compared with placebo-treated pigs (at 30 minutes P < .05 and at 120 minutes P < .01). DO2I and VO2I were poorly correlated in all pigs treated with nimodipine and in 3 of 7 animals treated with placebo, suggesting supply independency in these animals. This difference between groups was significant (P < .05). CONCLUSIONS: Our findings suggest that in nimodipine-treated animals, a lower oxygen deficit or a better redistribution of regional blood flow occurred after circulatory arrest and resuscitation. PMID- 8199651 TI - The effect of adrenergic agonists on the systemic response to hemorrhage. AB - PURPOSE: Systemic blood loss elicits a variety of reflex cardiovascular responses, which preserve cardiac output as possible and preserve arterial blood pressure when cardiac output decreases. When compensatory venoconstriction is exhausted, hemorrhage reduces oxygen delivery (QO2), and systemic vasoconstriction competes with local metabolic vasodilation to preserve tissue oxygen uptake (VO2). Through their effects on vascular tone and blood flow distribution, adrenergic agents might interfere with the physiological responses to reduced O2 delivery. This study was designed to determine the effects of dobutamine and norepinephrine on oxygen extraction and systemic vascular resistance during progressive hemorrhage. METHODS: We infused dobutamine or norepinephrine into anesthetized, ventilated dogs and measured the systemic vascular resistance, oxygen consumption, and oxygen extraction ratio as oxygen delivery (blood flow) was reduced by blood withdrawal. Four groups were compared: control (saline), dobutamine (10 micrograms/kg/min), high-dose norepinephrine (1.0 microgram/kg/min), and low-dose norepinephrine (0.1 microgram/kg/min). RESULTS: High-dose norepinephrine increased oxygen demand but did not alter extraction significantly at the critical point. Neither low-dose norepinephrine nor dobutamine affected oxygen extraction during hemorrhage. Dobutamine and norepinephrine both ablated the increase in systemic vascular resistance that accompanies hemorrhage. Low-dose norepinephrine was not different from control. CONCLUSIONS: Norepinephrine and dobutamine appear to block reflex vasoconstriction, and mechanistic explanations for this finding remain speculative. Despite inhibition of reflex vasoconstriction, neither dobutamine nor norepinephrine significantly impaired oxygen extraction during hemorrhage. PMID- 8199652 TI - The effects of intravenous L-arginine supplementation on systemic and pulmonary hemodynamics and oxygen utilization during group B streptococcal sepsis in piglets. AB - PURPOSE: In these investigations, three questions were addressed. First, to what extent did inhibition of endothelium-derived relaxation factor (EDRF) mimic the hemodynamic disturbances noted in a piglet model of neonatal group B streptococcal (GBS) sepsis? Second, to what extent would an attempt to augment EDRF production reverse the hemodynamic effects of continued GBS infusion in septic piglets? Third, to what extent would an attempt to augment EDRF production affect hemodynamics in piglets who were not septic. METHODS: Six experimental protocols were studied in a total of 25 piglets. The extent to which inhibition of EDRF resembled GBS sepsis was determined by comparing hemodynamic observations during (1) EDRF inhibition (using a competitive inhibitor of nitric oxide synthase, N-nitro-L-arginine [NNLA], 80 mg/kg) with (2) GBS infusion. Next, the extent to which an attempt to augment EDRF production would reverse hemodynamic effects of neonatal GBS sepsis was addressed by comparing hemodynamic observations during (3) administration of pharmacological doses (300 mg/kg) of the EDRF precursor L-arginine (L-ARG) in piglets receiving continuous GBS infusion with (4) continuous GBS infusion in piglets who did not receive L-ARG. Finally, to provide an additional comparison for the protocols described above, the effects of (5) L-ARG in piglets pretreated with NNLA were compared with (6) L ARG infusion in normal piglets, who had received neither GBS nor NNLA. RESULTS: Both NNLA and GBS increased systemic and pulmonary vascular resistance and decreased systemic cardiac output. For equivalent reductions in cardiac output, GBS preferentially vasoconstricted the pulmonary versus systemic circulation, whereas NNLA produced equivalent vasoconstriction in both circulations. During continuous GBS infusion, L-ARG attenuated the progressive increase in systemic and pulmonary vascular resistance, pulmonary artery pressure, and pulmonary vascular resistance/systemic vascular resistance. L-ARG infusion in nonseptic, non-NNLA-treated piglets had no significant effect on any hemodynamic variable. L ARG infusion in piglets pretreated with NNLA restored hemodynamic values towards those of piglets treated with L-ARG alone. CONCLUSIONS: EDRF inhibition with NNLA appeared to model GBS infusion partially but not completely. L-ARG appeared to produce desirable hemodynamic effects during GBS sepsis when compared with the consequences of ongoing GBS infusion without L-ARG. Given the constellation of increased pulmonary and systemic vascular resistance often observed during neonatal GBS sepsis in human infants, all these effects of L-ARG, if extrapolated from our piglets to the clinical arena, would appear to be beneficial. Particularly in the context of deleterious consequences resulting shunting or right ventricular decompensation from increased afterload), L-ARG administration might prove clinically useful. PMID- 8199653 TI - Role of neutrophil-endothelial cell adhesion in inflammatory disorders. AB - Polymorphonuclear leukocytes are armed with an impressive arsenal of bactericidal agents that allow these cells to play a vital role in host defense against invading pathogens. However, these same agents can produce extensive cellular damage in host tissues when leukocytes are activated during inflammatory conditions. Recognition of this fact, when coupled with the observation that leukocyte adhesion to post-capillary venules is a critical first step in the inflammatory process, has led to the development of the concept that inhibition of neutrophil-endothelial cell adhesion (NECA) may represent a novel therapeutic strategy for the prevention of leukocyte-dependent injury in inflammatory conditions. Indeed, pharmacological or immunologic inhibition of NECA reduces cellular injury, dysfunction, and necrosis induced by ischemia/reperfusion, circulatory shock and resuscitation, organ transplantation, cardiopulmonary bypass, frostbite, and thermal trauma. NECA also appears to play an important role in the pathobiology of airway inflammation and asthma, pulmonary oxygen toxicity, arthritis, bacterial meningitis, and cerebral malaria. The aim of this review is to summarize the evidence implicating NECA in the pathogenesis of these inflammatory conditions. PMID- 8199654 TI - Hormonal profiles in a canine model of the brain-dead organ donor. AB - PURPOSE: The aim of the present study was to determine the effect of brain death on the circulating hormone levels. METHODS: Serum total thyroxine (TT4), total 3,3,5' triiodothyronine (TT3), free thyroxine (FT4), free 3,3,5' triiodothyronine (FT3), reverse 3,3',5' triiodothyronine (RT3) and plasma cortisol (CORT), norepinephrine (NE), epinephrine (EPI), dopamine, insulin (INS), and glucagon (GLUC) concentrations were measured before and for 5 hours after the maintenance of brain death (BD, n = 8), sham-brain death induction (SHAM, n = 3), and the operative procedure alone (time control, n = 3). Brain death in the canine model was induced by increasing and maintaining intracranial pressure above systolic arterial pressure. RESULTS: Brain death led to a persistent, significant decrease in mean arterial pressure (121 +/- 6 v 40 +/- 4 mm Hg at 5 hours). A significant decrease in the TT4, TT3, FT4, and FT3 concentrations was seen during the experiment for all three groups with the exception of TT4 in the SHAM group; no significant difference was found among the three groups for any of the time points. RT3 was found to increase after the induction of brain death in the BD (n = 5) group. The CORT levels in the BD group were significantly less than the other two groups for all time points 30 minutes after the induction of brain death. The mean 30- to 300-minute plasma NE and EPI levels in the SHAM group were statistically greater than the BD group. The plasma glucose in the BD group was maintained between 60 and 140 mg/dL whereas the trends of the INS/glucose and GLUC/glucose ratios in the BD group were appropriate for the plasma glucose level. CONCLUSIONS: The operative procedure alone led to the decrease in the plasma thyroid hormone levels. The inability of the BD group to increase plasma CORT, NE, and EPI may contribute to the hemodynamic deterioration and eventual somatic death. PMID- 8199655 TI - Report of the American-European Consensus conference on acute respiratory distress syndrome: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Consensus Committee. AB - The acute respiratory distress syndrome (ARDS), a process of nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, carries a high morbidity rate, mortality rate (10% to 90%), and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged and may be different in Europe. Part of the reason for these uncertainties is the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those who wish to know the true incidence and outcome of this clinical syndrome are stymied. The European American Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS. PMID- 8199656 TI - Struggles and successes: experiences of a beta test site. AB - More than 400 hospitals participated in the first stages of beta testing for Joint Commission-developed indicators. One hospital chosen as a beta test site describes how this experience led to an evaluation of its own performance. PMID- 8199657 TI - Using health care outcomes to improve patient care in the NICU. AB - The authors describe their use of outcomes research in improving the care of infants in a ten-hospital network of neonatal intensive care units. Improvements in the processes of care for infants born with very low birth weights, and those suffering from chronic lung disease and nosocomial infections, are among the issues discussed. PMID- 8199658 TI - Short-form measures of physician and employee judgments about hospital quality. PMID- 8199659 TI - Quality improvement project reviews: a tool to accelerate the transformation. AB - Management can use quality improvement project reviews to provide guidance and encouragement, promote learning, and display its commitment to quality improvement. This article suggests ways to conduct reviews. PMID- 8199660 TI - Evaluating new ways of managing quality: an interview with Stephen M. Shortell and Jim O'Brien. Interview by Alan B. Cohen. PMID- 8199661 TI - Survey of construction workers repeatedly exposed to chlorine over a three to six month period in a pulpmill: I. Exposure and symptomatology. AB - OBJECTIVE: The admission to hospital of three construction workers with acute respiratory distress caused by inhalation of chlorine gas prompted the inspection of a building site located in a kraft pulpmill. The accidental emissions had taken place in the bleach plant and the construction workers assigned there were surveyed to uncover possible large scale health effects. DESIGN AND PARTICIPANTS: A questionnaire was presented to 281 workers (participation rate = 97%); 257 workers reported an average of 24 exposure episodes to chlorine and derivatives over a three to six month period. The air monitoring data available from the pulpmill's industrial hygienist were not useful in linking specific events reported by the workers to environmental conditions in the bleach plant. RESULTS: Over 60% of the workers described a characteristic flu like syndrome that lasted for an average of 11 days and was exacerbated by new bouts of exposure. Irritation of the throat (78%) and eyes (77%), cough (67%), and headache (63%) were the most often reported symptoms. Shortness of breath was reported by 54% of the participants and was not associated with age, smoking state, or history of asthma or chronic bronchitis. First aid self referral was associated with significantly greater reporting of most symptoms, including dyspnoea and cough. A significantly greater proportion of workers in the dyspnoea group had gone at least once for first aid care after a gassing incident (64% as opposed to 48%, p = 0.008). Throat irritation and cough persisted for mean intervals of eight and 11 days respectively. A flu like syndrome lasted for an average of 20 days. Seventy one subjects were considered to be a moderate to high risk of having persisting respiratory symptoms. CONCLUSION: Throat and eye irritation as well as cough and flu like symptoms are frequent occurrences after repeated accidental inhalation of chlorine. Subjects who consulted first aid care stations after a gassing incident are more likely to have persisting dyspnoea. PMID- 8199662 TI - Survey of construction workers repeatedly exposed to chlorine over a three to six month period in a pulpmill: II. Follow up of affected workers by questionnaire, spirometry, and assessment of bronchial responsiveness 18 to 24 months after exposure ended. AB - OBJECTIVE: The aim was to determine the prevalence of persistent respiratory symptoms and bronchial hyper-responsiveness due to reactive airways dysfunction syndrome in a population of construction workers at moderate to high risk of developing the syndrome, at an interval of 18 to 24 months after multiple exposures to chlorine gas during renovations to a pulp and paper mill. DESIGN AND PARTICIPANTS: 71 of 289 exposed workers (25%) were identified on the basis of an exposure and the onset of respiratory symptoms shortly after this event (moderate to high risk). A standardised respiratory questionnaire was first presented, followed by spirometry and a methacholine inhalation test on those whose questionnaire suggested the persistence of respiratory symptoms. RESULTS: 64 of 71 (90%) subjects completed the respiratory questionnaire at the time of the follow up. The questionnaire suggested a persistence of respiratory symptoms in 58 of the 64 workers (91%). Of the 58 subjects, 51 underwent spirometry and assessment of bronchial responsiveness. All of them used bronchodilators as required (not regularly) and four required inhaled anti-inflammatory preparations. Sixteen had bronchial obstruction (forced expiratory volume in one second) (FEV1 < 80% predicted) and 29 showed significant bronchial hyper responsiveness. CONCLUSION: Of the subjects (n = 71) who were at moderate to high risk of developing reactive airways dysfunction syndrome after being exposed to chlorine and were seen 18 to 24 months after exposure ended, 58 (82%) still had respiratory symptoms, 16 (23%) had evidence of bronchial obstruction, and 29 (41%) had bronchial hyper-responsiveness. PMID- 8199663 TI - Biological monitoring of cyclophosphamide and ifosfamide in urine of hospital personnel occupationally exposed to cytostatic drugs. AB - The occupational exposure of 21 nurses and pharmacy personnel from eight hospitals to cyclophosphamide and ifosfamide was determined by quantifying the amount of the drugs handled and by measuring the urinary excretion of the unmetabolised substances. Preparing antineoplastic drugs for intravenous treatment was the major task of all study participants. Twenty four hour urine was collected on days when cyclophosphamide and/or ifosfamide were mixed, on average 3900 mg cyclophosphamide and/or 5900 mg ifosfamide. The analyses were performed by gas chromatography with electron capture, detection limit 2.5 micrograms/24 hour urine. Despite standard safety precautions, including a vertical laminar air flow safety cabinet and gloves, cyclophosphamide was detected in 12 of 31 and ifosfamide in four of 21 urine samples on days when the drugs were handled. Excretion of cyclophosphamide ranged from 3.5 to 38 micrograms/24 h (mean 11.4 micrograms/24 h) urine, ifosfamide from 5 to 12.7 micrograms/24 h (mean 9 micrograms/24 h) urine. Based on an excretion rate of 11.3% unmetabolised cyclophosphamide, the average amount excreted corresponded to an uptake of 101 micrograms cyclophosphamide. For ifosfamide the mean quantity incorporated was 20 micrograms assuming that 45% of the drug was excreted. Pertaining to the doses handled, the uptake of cyclophosphamide and ifosfamide was estimated to be approximately 0.0025% and 0.0004% respectively. Despite time consuming purification procedures, gas chromatographic analysis is a suitable method for monitoring personnel occupationally exposed to cyclophosphamide and ifosfamide and is a major contribution to the evaluation of potential health risks of exposed personnel. PMID- 8199664 TI - Airways obstruction, coal mining, and disability. AB - It has recently been suggested that the inhalation of coal in the absence of complicated coal workers' pneumoconiosis (CWP) or smoking can lead to disabling airways obstruction. The cause of such obstruction has been variously attributed to emphysema or bronchitis. The frequency of significant airways obstruction in a group of United States coal miners seeking compensation for occupationally induced pulmonary impairment was therefore determined. In a sample of 611 "Black Lung" claimants there was only one subject who was a non-smoker and who in the absence of other non-occupationally related diseases,--for example, asthma and bronchiectasis--had sufficient airways obstruction to render it difficult for him to carry out hard labour. An alternative explanation for his reduced ventilatory capacity other than coal dust or smoking may be available. If the inhalation of coal dust in the absence of smoking and complicated CWP ever induces sufficient ventilatory impairment to preclude a miner from working, it is indeed rare. PMID- 8199665 TI - Findings from high resolution computed tomography of the lung and pleura of symptom free workers exposed to amosite who had normal chest radiographs and pulmonary function tests. AB - The lungs of 50 symptom free workers exposed to amosite and with normal pulmonary function tests were examined by high resolution computed tomography (HRCT). Twenty five had normal standard chest radiographs whereas the other 25 had radiographs interpreted as near normal (International Labour Office profusion score < 0/1 or suspected pleural plaques). In 13 of the workers the results of HRCT were negative; in 22 pleural plaques were found, in five there was only parenchymal involvement, and 10 had both pleural and parenchymal changes. The mean duration of exposure to amosite was significantly longer for the subjects with parenchymal signs than for those with normal parenchyma and for the workers with pleural plaques than for those with normal pleura and lung parenchyma. The prevalence of identified pleural and parenchymal abnormalities in the 50 workers was also significantly higher than in a reference group without exposure to asbestos. It is concluded that HRCT may detect initial lung and pleural involvement in symptom free workers exposed to amosite and the mean duration of exposure is longer for subjects with parenchymal or pleural involvement. PMID- 8199666 TI - Pleural mesothelioma and exposure to asbestos: evaluation from work histories and analysis of asbestos bodies in bronchoalveolar lavage fluid or lung tissue in 131 patients. AB - Exposure to asbestos was evaluated in 131 patients with pleural malignant mesothelioma in the Paris area between 1986 and 1992 using data from a detailed specific questionnaire and light microscopy analysis of the retention of asbestos bodies in bronchoalveolar lavage fluid or lung tissue. Probable or definite exposure to significant levels of asbestos dust was identified in only 48 (36.6%) subjects, and significant asbestos body counts (above 1 asbestos body/ml in bronchoalveolar lavage fluid or 1000 asbestos bodies/g of dry lung tissue) were found in only 45 (34.3%) subjects. Overall 50 subjects had experienced exposure to only low levels of asbestos or no exposure at all and showed no significant retention of asbestos bodies in the biological sample analysed. Previous studies have shown that light microscopy may be useful in the identification of subjects with previous exposure to asbestos. In this study, apart from cases with obvious exposure to asbestos, a large group of subjects seemed to have a history of exposure or lung retention of asbestos bodies suggestive of very low levels of cumulative exposure, similar to those described in the general population. PMID- 8199667 TI - Exposure to polycyclic aromatic hydrocarbons in petrochemical industries by measurement of urinary 1-hydroxypyrene. AB - Biological monitoring of exposure of workers to polycyclic aromatic hydrocarbons (PAHs) in petrochemical industries was performed by the measurement of urinary excretion of 1-hydroxypyrene. In 121 of the 462 workers studied (both smokers and non-smokers) who had had no recent occupational exposure to PAHs a median 1 hydroxypyrene concentration of 0.21 micrograms/g creatinine was found. The upper limit of the 95% confidence interval in these workers of 0.99 micrograms/g creatinine was used as the upper normal value for industrial workers. Urinary 1 hydroxypyrene concentrations were measured in workers involved in manufacture and maintenance operations in oil refineries (13 studies in eight different settings), in workers manufacturing or handling products containing PAHs in chemical plants (five studies in three settings) and laboratories (four studies), and in workers digging soil contaminated with PAHs (three studies). In most studies in oil refineries 1-hydroxypyrene concentrations were only marginally greater than the values measured in the 121 workers with no recent occupational exposure to PAHs. This was also the case in maintenance operations with higher potential exposure to PAHs, indicating that personal protection equipment was generally adequate to prevent excessive exposure. The studies in chemical plants also showed that exposure to PAHs is low. An exception was the workers engaged in the production of needle coke from ethylene cracker residue, where increased urinary 1-hydroxypyrene concentrations were measured. The excretion of 1 hydroxypyrene by the operators and maintenance workers of this plant was investigated in relation to potential methods of exposure to PAHs. Dermal and inhalatory exposure were both significant determinants of exposure to PAHs. PMID- 8199668 TI - Chronic interstitial nephropathy after plasma cutting in stainless steel. AB - Chromium is nephrotoxic in experimental animals. In subjects with acute chromium intoxication acute nephritis has been reported and renal function has been affected in chromium exposed workers with a high urinary chromium concentration. Chronic kidney disease after long term occupational exposure to chromium has, however, not been reported previously. A case report is presented concerning a 48 year old man who was diagnosed with chronic interstitial nephropathy. He had worked for nine years as a plasma cutter of stainless steel and had thereby been exposed to smoke containing chromium. At the time of diagnosis his blood chromium concentration was seven times higher and his urinary chromium concentration six times higher than reference values. Taking into account the nephrotoxicity of chromium and the high chromium burden of this patient it is considered likely that his exposure to smoke from plasma cutting of stainless steel was the cause of his chronic interstitial nephropathy. PMID- 8199669 TI - Case-control study of risk factors for disease in the neck and shoulder area. AB - A case-control study was performed to elucidate the strength of the relation between musculoskeletal disorders in the neck and shoulders and physical, organisational, and psychosocial aspects of the work environment. Cases were identified as those persons who consulted a physician in a community in southern Sweden for new musculoskeletal disorders in the neck and shoulders during a study period from August 1988 to the end of October 1989. One hundred and nine cases were collected and clinically examined. The cases also answered the Nordic questionnaire on symptoms as well as a questionnaire on work conditions and background factors. Controls were drawn as a random sample of the working population in the community where the cases appeared. A total of 637 controls answered the same questionnaires as the cases. Odds ratios (ORs) were calculated by logistic regression. The odds ratios were 11.4 for women, 4.9 for immigrant background, and 3.7 for current smoking. To exercise rarely, compared with often, appeared as a preventive factor with an OR of 0.3. The ORs for various determinants of physical work load were 7.5 for repetitive movements demanding precision, 13.6 for light lifting, 3.6 for uncomfortable sitting positions, 4.8 for work with lifted arms, and 3.5 for a rushed work pace. Regarding work organisational determinants, the ORs were 16.5 for ambiguity of work role (uncertainty whether the person could manage the work) 2.6 for low quality work, and 3.8 for high demands on attention. Several of the determinants showed a significant dose-response relation with disease. It seems that work organisation and psychosocial work conditions are as important determinants for disease in the neck and shoulders as are the physical work conditions. PMID- 8199670 TI - Chronic elemental mercury intoxication: clinical and field studies in lampsocket manufacturers. AB - Four workers chronically exposed to elemental mental mercury in a lampsocket manufacturing factory were studied. The clinical manifestations were severe in one, mild in another, and suspicious in the remaining two. Correlation between severity of clinical features and increased urinary mercury concentrations was found. The time weighted average mercury concentrations were 0.945 mg/m3 and 0.709 mg/m3 for two workers in one room and 0.225 mg/m3 in the other. After stopping exposure, the workers recovered spontaneously or with D-penicillamine treatment within six months. It is concluded that recovery from chronic elemental mercury intoxication may be complete when patients are removed early from the exposure environment. The hazard of mercury intoxication in recycling of waste substances is emphasised. PMID- 8199671 TI - Differences in the effects of two hexachlorobiphenyls on superoxide generation by polymorphonuclear leucocytes stimulated by N-formyl-methionyl-leucyl phenylalanine and phorbol myristate acetate. AB - The effects of hexachlorobiphenyls (HCBs) on superoxide (O2-) generation by guinea pig polymorphonuclear leucocytes were examined. 2,3,6,2',3',6'-HCB by itself had only a weak inductive effect on O2- generation. This compound, however, enhanced O2- generation stimulated by N-formyl-methionyl-leucyl phenylalanine (FMLP) about twofold, but not the generation induced by phorbol myristate acetate (PMA). On the other hand, 3,4,5,3',4',5'-HCB suppressed O2- generation stimulated by both FMLP and PMA. The inhibitory potency of this compound was far greater with PMA (ID50, 5 microM) than with FMLP (ID50, 40 microM). PMID- 8199672 TI - Retention and clearance of inhaled ceramic fibres in rat lungs and development of a dissolution model. AB - Male Wistar rats were exposed to aluminium silicate ceramic fibres by inhalation to study pulmonary deposition, clearance, and dissolution of the fibres. Rats were killed at one day, one month, three months, and six months after the termination of exposure. After exposure, fibres greater than 50 microns in length were seen with a scanning electron microscope in the alveolar region of the lung. Fibres were recovered from the lungs with a low temperature ashing technique and their number, diameter, and length were measured by scanning electron microscopy. The number of fibres remaining in the lungs declined exponentially with time after exposure and their silicon content also fell. The geometric median diameter of fibres decreased linearly with time. By six months after exposure, the surface of fibres recovered from the lungs had an eroded appearance. The results suggest that ceramic fibres are physically cleared from the lung and that they show signs of dissolution. Finally, the results were used to develop a theoretical model of fibre dissolution that gives a satisfactory fit to the experimental data. PMID- 8199673 TI - Impairment of lipoglycoprotein metabolism in rat liver cells induced by 1,2 dichloroethane. AB - BACKGROUND: 1,2-Dichloroethane (DCE) is a volatile liquid readily absorbed through dermal, digestive, or inhalatory routes. After inhalation or oral administration to rats, death occurs within a narrow range of concentrations (six hour LC50 = 5100 mg/m3). Exposure to single high doses of DCE resulted in adverse effects on the central nervous system, liver, kidneys, adrenals, and lungs. The liver showed fatty changes and hepatocellular necrosis with haemorrhage. These injuries are probably related to changes in several cell functions and constituents. Therefore, it was decided to investigate whether DCE was capable of impairing the secretion of hepatocellular lipoglycoproteins acting both at the level of the Golgi apparatus and endoplasmic reticulum. METHODS: Isolated hepatocytes of Wistar rats were prelabelled with two precursors of lipoglycoproteins 3H-Na-palmitate and 14C-glucosamine, and then exposed to concentrations of DCE from mean (SD) 4.4 (0.03) to 6.5 (0.02) mM for different durations ranging from five to 60 minutes. To measure lipid and sugar bound radioactivity, a preliminary separation of cell homogenate, cytosol, total microsomes, Golgi apparatus, and lipoglycoproteins secreted into cell suspension medium was carried out. RESULTS: After five minutes of exposure, DCE did not induce obvious changes in cell viability or lactic dehydrogenase leakage, but a significant (p < 0.01) depletion of reduced glutathione content was seen (40.10 (4.3) nM/10(6) cells). Furthermore, the cells poisoned by DCE started to show noticeable accumulation of 3H-Na-palmitate in the Golgi apparatus after five minutes (5103 (223) dpm/10(6) cells) and in the microsomes after 15 minutes (85,470 (7190) dpm/10(6) cells). There was a simultaneous significant increase in 14C-glucosamine content in the Golgi apparatus (690 (55) dpm/10(6) cells) and the microsomes (15,975 (2035) dpm/10(6) cells). The specific radioactivity of lipid and sugar moieties incorporated in secreted lipoglycoproteins was already significantly reduced after only five minutes of exposure (480 (57) dpm/10(6) cells for lipids, and 315 (45) dpm/10(6) cells for sugars). CONCLUSIONS: Overall, DCE, like other haloalkanes, produces a block of secretion of hepatocellular lipoglycoproteins as early as five minutes after poisoning. The simultaneous percentage increases into Golgi apparatus and microsomes of lipid and sugar bound radioactivity suggest that lipid retention at the sites of processing of lipoglycoproteins would probably play an important part in the early stages of cellular accumulation of fat after exposure to DCE. PMID- 8199674 TI - Increase in neuropsychiatric symptoms after occupational exposure to low levels of styrene. PMID- 8199675 TI - The correction of urinary mercury concentrations in untimed, random samples. PMID- 8199676 TI - Research priorities in occupational medicine: a survey of United Kingdom medical opinion by the Delphi technique. AB - An attempt to achieve an agreed set of priorities for research in occupational medicine was undertaken by the Delphi technique. Fifty three senior practitioners of occupational medicine in academe (25) and industry or government (28) were canvassed about their views and choices for priority activity. Forty six (86%) responded to the initial enquiry and 48 (91%) provided rank order choices from a second, more detailed questionnaire. The first priority for more research on the natural history of work related ill health identified musculoskeletal disorders of the back and upper limbs followed by asthma, accidents, skin disorders, vibration induced disease, suicide and depression, and finally hearing loss. The second priority area was audit and particularly the need for its use in occupational health screening procedures. Environmental impact of industrial activity was third with the community health effects being more important than individual health effects. Stress related disease was fourth with emphasis on risk factors. The fifth area was neuropsychological effects of work exposures particularly the need for more research on diagnostic tests. Other assorted areas of concern were the cost effectiveness of occupational health, risk assessment, reproductive hazards, the effects of pharmacological agents, and the development of biomarkers as early evidence of an exposure effect. The remarkable degree of unanimity on the issues and choices and the general agreement between physicians from academe and industry on what constitute the priorities warrants further discussion and positive action. PMID- 8199677 TI - An investigation of brain tumours and other malignancies in an agricultural research institute. AB - A historical cohort study was carried out in an agricultural research institute in the Republic of Ireland to investigate a perceived excess of cancer deaths among employees. The objectives of the study were (a) to confirm whether or not total or cause specific death rates among selected employees were higher than expected based on national figures, and to quantify any excess, and (b) to identify centres and employee grades associated with any excess risk. The cohort comprised all administrative, research, and technical staff employed for at least two years between 1960 and 1980, giving a final total for analysis of 1323 employees. Employment history was categorised by place of work and employment grade. Deaths among the cohort were identified and causes of deaths verified. Overall the cohort had a lower than expected mortality compared with national rates (O/E = 0.67). Female deaths were too few for analysis but, among the male employees, there was an excess of all cancers (O/E = 1.24; 95% confidence interval (95% CI) 0.8-1.9), in particular brain cancer (O/E = 4.69; 95% CI 1.2 11.4) and bladder cancer (O/E = 9.31, 95% CI 1.9-27.2). The pattern of brain tumour deaths was consistent with an occupational aetiology but it was not possible to identify specific exposures associated with the excess. All four cases occurred among research workers in the plant and soil science area. The pattern of bladder cancers was difficult to interpret. The authors are at present participating in a multicentre study to further investigate cancer risk in laboratory workers. PMID- 8199678 TI - Sickness absence in diabetic employees at a large engineering factory. AB - It is not known whether employees who have diabetes mellitus lose more time from work due to sickness than non-diabetic employees. A study was undertaken to compare sickness absence in 91 diabetic with 91 non-diabetic employees matched for sex, age, and occupation. Although sickness absence was greater in the diabetic group this was not significant. Mean sickness absence for the diabetic employees and controls was 32 v 20 days/year (95% confidence interval -5 to 29 days). Because of the large variability in sickness absence in both diabetic and non-diabetic employees, a study of this size is probably not sufficiently powerful to detect a difference. PMID- 8199679 TI - A case-control study of chronic neuropsychiatric disease and organic solvent exposure in automobile assembly plant workers. AB - A case-control study of chronic neurological and psychiatric disease and occupational exposure to solvents was carried out in eight automobile assembly plants. Cases included 299 subjects who were granted medical disability retirement in 1980-8. Two control groups were selected, the first from those granted retirement in the same period because of medical disability from causes unrelated to solvent exposure. The second included hourly employees from the plant population. In these facilities, solvent exposures tended to be short term and low level, although common: the average duration of exposure was 2.3 years; about 41% experienced at least one day of exposure. Of those exposed, 46% had less than one year of exposure. Results for all psychiatric disease combined (273 cases) suggested that cases had lower exposures than either control group, regardless of how exposure was expressed. Results could not be explained by conventional confounding exposures or characteristics or by usual manifestations of the healthy worker effect. By contrast, chronic neurological disease, and multiple sclerosis in particular, seemed to be associated with exposure, although few cases were identified and observed increases in risk were not statistically significant. PMID- 8199680 TI - Mortality in uranium miners in west Bohemia: a long-term cohort study. AB - A cohort of 4320 uranium miners in West Bohemia who started work at the mines during 1948 to 1959 and worked there for at least four years were followed up to the end of 1990 to determine cause specific mortality risks in relation to exposures in the mines. The miners had experienced high radon exposures, on average 219 working level months during their uranium mining careers, for which detailed measurements were available. They had also been exposed to high arsenic levels in one of the two major mines, and to dust. New follow up methods, not previously used for occupational cohorts in Czechoslovakia, were utilised. By the end of follow up 2415 (56%) of the cohort were known to have died. Overall mortality was significantly raised compared with that in the general population (relative risk (RR) = 1.56, 95% confidence interval (95% CI) 1.50-1.63), with significantly raised risks of lung cancer (RR = 5.08, 95% CI 4.71-5.47), accidents (RR = 1.59, 95% CI 1.34-1.87), homicide (RR = 5.57, 95% CI 2.66-10.21), mental disorders (RR = 5.18, 95% CI 2.83-8.70), cirrhosis (RR = 1.51, 95% CI 1.16 1.94), and non-rheumatic circulatory diseases (RR = 1.16, 95% CI 1.08-1.25). The relative risk of lung cancer was greatest four to 14 years after entry to the mines. Relative risks for homicide and accidents were raised up to 25 years from entry but not after this. Substantial significantly raised risks at 15 to 24 years after entry occurred for cirrhosis, non-rheumatic circulatory diseases,a nd pneumonia and other respiratory infections. Sizeable significantly raised risks at 25 and more years after entry, but not earlier, were present for mental disorders, tuberculosis, and non-malignant non-infectious respiratory conditions. No specific causes showed risks significantly related to age at entry to mining. Risk of lung cancer was significantly positively related to radon exposure, estimated arsenic exposure, and duration of work in the mines, but no other cause was significantly positively related to these variables. The raised risk of lung cancer in uranium miners, which is well established, is related aetiologically to radon exposure, and in the present cohort it may also in part have been due to exposure to arsenic. The raised risks of accidents, tuberculosis, and non infectious respiratory diseases have also been seen in other uranium mining cohorts, and are likely to reflect the dangerous and dusty working conditions and the confined spaces in which work occurred. The cirrhosis and homicide deaths probably related to the lifestyle associated with mining. The raised risk of circulatory diseases does not seem to be related to radon or arsenic exposure; its causes are unclear. The use of multiple follow up methods was found to be mortality in the cohort. PMID- 8199681 TI - Mortality among a cohort of United Kingdom steel foundry workers with special reference to cancers of the stomach and lung, 1946-90. AB - OBJECTIVE: The aim was to describe cause specific mortality among steel foundry workers and to determine if any part of the experience may be due to occupation. DESIGN: Historical prospective cohort study. SETTING: Nine steel foundries in England and one in Scotland. SUBJECTS: 10,438 male production employees first employed in the period 1946-65 and with a minimum period of employment of one year. MAIN OUTCOME MEASURES: Observed and expected numbers of deaths for the period 1946-90. RESULTS: Compared with the general population of England and Wales, standardised mortality ratios (SMRs) for all causes and all neoplasms were 115 (observed deaths (Obs) 3976) and 119 (Obs 1129) respectively. Statistically significant excesses were found for cancer of the stomach (Obs 124, expected deaths (Exp) 92.5, SMR 134, 95% confidence interval (95% CI) 111-160) and cancer of the lung (Obs 551, Exp 378.3, SMR 146, 95% CI 134-158). A raised SMR (153) was also found for non-malignant diseases of the respiratory system. Classifications of jobs attracting either higher dust or higher fume exposures did not usefully predict these increased SMRs. Poisson regression was used to investigate risks of mortality from all cancers, cancer of the stomach, cancer of the lung, and non malignant diseases of the respiratory system associated with duration of employment in the foundry area, the fettling shop, the foundry area/fettling shop, and the industry in general. Monotonic dose-response relations were not found, although there were positive trends for lung cancer and employment in the foundry area/fettling shop (1.0, 1.21, 1.44, 1.26) and for diseases of the respiratory system and employment in the fettling shop (1.0, 1.37, 1.18, 1.35). CONCLUSIONS: Confident interpretation of the causes of the raised SMRs was not possible. There was limited evidence of an occupational role in the excesses of lung cancer and diseases of the respiratory system. Smoking history was shown, in an indirect way, to be an unlikely explanation. PMID- 8199682 TI - Mortality, morbidity, and haematological results from a cohort of long-term workers involved in 1,3-butadiene monomer production. AB - A retrospective mortality analysis and prospective morbidity and haematological analyses were performed for Shell Deer Park Manufacturing Complex (DPMC) male employees who worked in jobs with potential exposure to 1,3-butadiene from 1948 to 1989. 614 employees qualified for the mortality study (1948-89), 438 of those were still employed during the period of the morbidity study (1982-9), and 429 of those had haematological data available for analysis. Industrial hygiene data from 1979 to 1992 showed that most butadiene exposures did not exceed 10 ppm (eight-hour time weighted average (8 hour TWA)), and most were below 1 ppm, with an arithmetic mean of 3.5 ppm. 24 deaths occurred during the mortality study period. For all causes of death, the standardised mortality ratio (SMR) was 48 (95% confidence interval (95% CI) = 31-72), and the all cancer SMR was 34 (95% CI = 9-87). There were only two deaths due to lung cancer (SMR 42, 95% CI = 5-151) and none due to lymphohaematopoietic cancer (expected = 1.2). Morbidity (illness absence) events of six days or more for the 438 butadiene employees were compared with the rest of the complex. No cause of morbidity was in excess for this group; the all cause standardised morbidity ratio (SMbR) was 85 (95% CI = 77-93) and the all neoplasms SMbR was 51 (95% CI = 22-100). Haematological results for the 429 with laboratory data were compared with results for the rest of the complex. No significant differences occurred between the two groups and the distributions of results between butadiene and non-butadiene groups were virtually identical. These results suggest that butadiene exposures at concentrations common at DPMC in the past 10-20 years do not pose a health hazard to employees. PMID- 8199683 TI - Past exposure to asbestos and combustion products and incidence of cancer among Finnish locomotive drivers. AB - Locomotive drivers in the steam engine era were exposed to asbestos during their vocational training for two years while training in workshops. Later in their career they had exposure to coal and diesel combustion products. To assess the level of earlier exposure historical working conditions were reconstructed and hygienic conditions were measured. The average exposure to asbestos (mainly anthophylline) fibres > 5 microns was 5.0 fibres/cm3. Incidence of cancer in a cohort of 8391 members of the Finnish Locomotive Drivers' Association, 1953-91, was analysed. The incidence of lung cancer and also total cancer was below the national average, probably due to the low prevalence of smoking among the drivers in the steam engine era. A four-fold risk of mesothelioma was found, most likely caused by exposure to asbestos. Also the observed 1.5-fold incidence of non melanoma skin cancer and 1.7-fold risk of cancer of the oral cavity and pharynx may be related to occupation. PMID- 8199684 TI - Exposure to stainless steel welding fumes and lung cancer: a meta-analysis. AB - Stainless steel welding is associated with exposure to metals including hexavalent chromium and nickel. This study is a meta-analysis of five studies of stainless steel welders and the occurrence of lung cancer. Asbestos exposure and smoking habits have been taken into account. The calculated pooled relative risk estimate was 1.94 with a 95% confidence interval of 1.28-2.93. This result suggests a causal relation between exposure to stainless steel welding and lung cancer. PMID- 8199685 TI - Clearance half life of mercury in urine after the cessation of long term occupational exposure: influence of a chelating agent (DMPS) on excretion of mercury in urine. AB - The elimination of mercury (Hg) in urine was investigated in 12 former chloro alkali workers exposed to metallic Hg vapour for two to 18 (median five) years. Morning urine samples were taken on several (median 9) occasions after change of employment or retirement. The median follow up time was 28 months. The decrease in concentration of Hg in urine (U-Hg) was well characterised by a one compartment model. Three different regression methods were used; non-linear least squares regression (NLSR), weighted non-linear least squares regression (WNLSR), and linear least squares regression (LLSR) after log transformation of the U-Hg data. The median half life from the WNLSR method was 55 days. There were no large differences in the half life estimates given by the WNLSR or the NLSR methods, but for five subjects the LLSR method gave poor fits. There was a non-significant tendency towards longer half lives with higher initial U-Hg. About three years after the cessation of occupational exposure a mobilisation test with 2,3 dimercaptopropane-1-sulphonate (DMPS) was performed on seven subjects. Excretion of Hg, copper (Cu), and zinc (Zn) in urine was estimated before and after the ingestion of 300 mg of DMPS. Treatment with DMPS increased 24 hour urinary excretion by a factor of 7.6 for Hg, 12 for Cu, and 1.5 for Zn. The relative increase in U-Hg was not significantly higher than that obtained in a previous study of an occupationally unexposed group. A major proportion (62%) of Hg excreted during 24 hours after DMPS appeared in the first six hours. PMID- 8199686 TI - Fibrogenic effect of wollastonite compared with asbestos dust and dusts containing quartz. AB - The distribution of length and diameter and the aspect ratio of crocidolite asbestos, a mineral substitute for asbestos (wollastonite), a manmade mineral fibre (glass wool), and synthetic fibres (polypropylene and polyacrylonitrite) were determined by light microscopy with phase contrast and, for crocidolite, also with transmission electron microscopy. The synthetic organic fibres and manmade mineral fibre used were of a size exceeding that considered respirable. Respirable materials were given to rats by the intratracheal method and after exposure for a standard time interval the main indices of fibrogenic effects--the total hydroxyproline content, the wet weight of the lung, and the total lipid content in the lung--were estimated. For wollastonite there was a significant increase in these variables in comparison with the controls. The fibrogenicity was considerably less than that of crocidolite and quartz. PMID- 8199687 TI - Liver function tests and urinary albumin in house painters with previous heavy exposure to organic solvents. AB - The serum activities or concentrations of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), albumin, gamma glutamyl transpeptidase (GGT), bilirubin (BIL), cholic acid (CHOL), chenodeoxycholic acid (CHENO), and transferrin with isoelectric point 5.7, and the urinary excretion of albumin were determined among male current or former house painters (n = 135) and house carpenters (n = 71) who had worked in their trades for at least 10 years before 1970. Workers who showed a value above the 90th percentile among the carpenters in at least one of the tests ASAT, ALAT, GGT, BIL, CHOL, or CHENO were regarded as showing "possible signs of liver dysfunction". Each participant's lifetime solvent exposure was evaluated by interview. The painters were divided into categories with low, intermediate, and heavy cumulative exposure during life (LTSE) or during the most exposed year (MEYSE). All participants stated none or slight recent exposure. The prevalence of possible signs of liver dysfunction increased with solvent exposure category according to LTSE as well as MEYSE with a numerically higher risk estimate in the heavy exposure category for MEYSE than for LTSE. ALP activity increased with exposure category according to both exposure estimates. This increase seemed to be due to an interaction between exposure to solvents and current or previous long term intake of medicines potentially toxic to the liver. None of these results was affected by whether or not the subjects had been exposed to solvents during the year before the investigation. The exposure to solvents was not significantly related to any other outcome variable. It is concluded that long term heavy exposure to solvents may elicit changes in conventional liver function tests indicative of a mild chronic effect on the liver. The findings also suggest that heavy solvent exposure during short time periods is a more likely cause of the findings than lifetime cumulative solvent exposure and that an interaction between solvent exposure and medicines potentially harmful to the liver may be important in the causation of the effects. PMID- 8199688 TI - Concentrations of phenol, o-cresol, and 2,5-xylenol in the urine of workers employed in the distillation of the phenolic fraction of tar. AB - Phenol (87.3 mg/l), p-cresol (58.6 mg/l), o-cresol (76.9 mg/l), and 2,5-xylenol (36.7 mg/l) were detected in the urine of workers employed in the distillation of the high temperature phenolic fraction of tar (carbolic oil). The concentrations of these compounds in the urine of non-exposed male workers was 11.7 mg/l, 25.7 mg/l, 68.1 micrograms/l, and 69 micrograms/l respectively. The excretion rates were 4.20 mg/h for phenol, 2.4 mg/h for p-cresol, 3.3 mg/h for o-cresol; and 1.5 mg/h for 2,5-xylenol. The highest concentrations of the mentioned compounds were detected in urine collected between eight and 10 hours from the beginning of exposure. The kinetics of excretion are considered. PMID- 8199689 TI - The presence of 1-naphthol in the urine of industrial workers exposed to naphthalene. AB - 1-Naphthol at concentrations ranging from 0.4 to 34.6 mg/l was found in urine collected directly after the end of the work shift from a group of industrial workers employed in distillation of naphthalene oil. The maximum excretion was found one hour after the end of the shift and the mean excretion rate was 0.57 mg/h. Coke plant workers exposed to naphthalene and other aromatic and polycyclic hydrocarbons also had 1-naphthol in their urine. Mean values were 0.89 mg/l (working with new technology) and 4.86 mg/l (working with old technology) and the excretion rates were 0.19 and 0.31 mg/h respectively. The maximum excretion was shifted to two to three hours after the end of the exposure. For non-exposed subjects the mean urinary 1-naphthol concentration was 120 micrograms/l and the excretion rate was 7.0 micrograms/h. PMID- 8199690 TI - Significance of modes of adherence in esophageal Candida albicans. AB - Although esophageal candidiasis is the most common form of Candida infection in the gastro-intestinal tract, little attention has been directed toward determining the mechanism of its infection. We have already clarified the existence of four modes of adherence of Candida albicans to the esophagus; attachment, subepithelial cell insertion, cavitation, and invasion. This study was undertaken to clarify the significance of each of these modes. Scanning electron microscopic observations were made of esophageal specimens from 8-week old rabbits infected with Candida albicans IFO 1060. In this study, attachment and subepithelial cell insertion were found to be the most frequent modes of adherence. Cavitation occurred following subepithelial cell insertion, while invasion occurred following attachment and subepithelial cell insertion. These results suggest that attachment and subepithelial cell insertion play the most important role in the initial stage of adherence. The ratios of these modes for living yeast cells were similar to those for dead yeast cells and beads. This suggests that Candida albicans can gain a foothold on the esophageal epithelium solely by physical contact, after which colonization occurs. PMID- 8199691 TI - Evaluation of diamine oxidase activity (DAO) in the rat intestinal mucosa by measuring expired 14CO2 after oral administration of 14C-putrescine. AB - This study was performed to investigate whether mucosal diamine oxidase activity could be assessed by measuring expired 14CO2 after oral administration of 14C putrescine. Immediately after giving 5 mu Ci of 14C-putrescine, the 14CO2 was collected at 1-h intervals for 8 h into a vial containing 1 ml of 10 mM hyamine hydroxide, 2 ml of ethanol, and an appropriate amount of phenolphthalein dye. The expired 14CO2 caused the color to disappear. The amount of 14CO2, determined by scintillation counting, reached a maximum 1 h after 14C-putrescine administration, and gradually decreased thereafter. A positive correlation between the mucosal diamine oxidase activity and the maximal expired 14CO2 value was obtained. There is no doubt that this test can be used to easily detect mucosal DAO activity and avoid the necessity of mucosal biopsy. PMID- 8199692 TI - Clinical significance of serum iron and ferritin in patients with colorectal cancer. AB - To clarify the significance of serum iron and ferritin as indicators of iron loss caused by continuous bleeding, and, thus, to determine their value as markers of colorectal cancer, values for the two were compared in male patients with early and advanced colorectal cancer and age-matched male controls. The mean value of serum iron levels in patients with advanced colorectal cancer was significantly decreased compared with values in patients with early colorectal cancer and controls, 50.5 +/- 38.6 micrograms/dl vs 93.0 +/- 32.1 micrograms/dl and 107.1 +/ 32.9 micrograms/dl, respectively (p < 0.001). The mean value of serum ferritin levels in patients with early and advanced colorectal cancer was also significantly decreased compared with controls, 80.5 +/- 35.0 ng/ml (p < 0.01) and 48.8 +/- 72.8 ng/ml (p < 0.001), respectively, vs 117.1 +/- 46.8 ng/ml. However, there was no significant difference between mean serum iron levels in patients with early colorectal cancer and controls. Eighteen (78.3%) of the 23 patients with advanced colorectal cancer and 3 (16.7%) of the 18 patients with early colorectal cancer had serum iron levels below 85 micrograms/dl and serum ferritin levels below 60 ng/ml. Levels of both serum iron and ferritin, without clinically evident anemia, are useful indicators of advanced colorectal cancer. PMID- 8199693 TI - Effects of glucagon on urinary excretion of urea and on plasma ammonia level in argininosuccinate synthetase deficiency. AB - Glucagon, a potent inducer of urea cycle enzymes, was administered subcutaneously, at a dose of 0.5 mg once a day, for 7 days to two citrullinemic patients. During this period, plasma NH3 levels in case 1 decreased significantly (P < 0.05 compared to levels before administration) and daily urinary excretion of urea N increased significantly (P < 0.05). For 1 week after the cessation of administration, the daily urinary excretion of urea N was significantly higher than the level before administration (P < 0.05), the plasma citrulline level during glucagon administration was lower than that before administration. In case 2, glucagon administration also decreased the plasma NH3 level (although the decrease was not statistically significant), and significantly increased daily urinary excretion of urea N (P < 0.05 compared to levels before administration). For 1 week after the cessation of glucagon administration the plasma citrulline level was significantly lower than that before administration (P < 0.05). These results indicate that glucagon significantly increases the urinary excretion of urea in the late onset form of argininosuccinate synthetase deficiency and that it may also decrease plasma NH3 levels in some patients with the deficiency. PMID- 8199694 TI - Immunohistochemical characterization of a monoclonal antibody to hyperplastic nodules induced in rat liver by chemical carcinogens. AB - To investigate the specific phenotype of hyperplastic nodules (HPN) in rat liver, we produced a monoclonal antibody (HAM-6). HAM-6 was a member of the mouse IgG1 class and was specific for hyperplastic nodules, as shown by cellular radioimmunoassay and immunohistochemical studies. The antigen recognized by HAM-6 was located in the rat HPN cell membrane. HAM-6 was also slightly reactive to rat hepatocellular carcinoma, but not to normal or fetal rat liver, other normal rat organs, human hepatocellular carcinoma, or human liver cirrhosis. That is, the antigen recognized by HAM-6 appeared to be differentiated and to occur during chemical carcinogenesis. HAM-6 may be a useful marker for the investigation of premalignant states in chemical carcinogenesis. PMID- 8199695 TI - Small hepatocellular carcinoma with intravascular tumor growth into the right atrium. AB - A 66-year-old man with ascites and marked edema in the lower extremities was suspected of having secondary Budd-Chiari syndrome due to primary liver cancer, based on imaging diagnosis, i.e., ultrasonography, computed tomography, and inferior venacavogram. At autopsy, an encapsulated small liver cancer was found to have extended into the inferior vena cava and right atrium. There have been few reports of small hepatocellular carcinoma with intravascular tumor growth into the right atrium. PMID- 8199696 TI - Effects of pravastatin and ursodeoxycholic acid on cholesterol and bile acid metabolism in patients with cholesterol gallstones. AB - To investigate the effects of pravastatin and ursodeoxycholic acid (UDCA) on cholesterol and bile acid metabolism in humans, 41 patients with cholesterol gallstone disease were allocated to four groups and treated with pravastatin (20 mg/day), UDCA (600 mg/day), both pravastatin and UDCA, or neither drug (control) for 1-2 weeks prior to elective cholecystectomy. Cholesterol 7 alpha-hydroxylase activity and serum levels of total 7 alpha-hydroxycholesterol were significantly increased by pravastatin and unaffected by UDCA. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity was markedly increased by pravastatin and decreased by UDCA. UDCA significantly decreased biliary cholesterol concentration and the cholesterol saturation index and prolonged the nucleation time; however, pravastatin alone had little effect on biliary lithogenicity. Serum total and low density lipoprotein (LDL)-cholesterol levels were reduced most by the combined administration of pravastatin and UDCA. In conclusion, at a dose of 20 mg/day, pravastatin increased bile acid synthesis but did not decrease biliary lithogenicity. UDCA had no significant effect on bile acid synthesis, but markedly decreased biliary lithogenicity. PMID- 8199697 TI - Amyloid deposition in the digestive tract in casein-induced experimental amyloidosis in mice. AB - In mice with casein-induced experimental amyloidosis, the incidence of amyloidosis in various organs was examined in relation to time, and the extent of amyloid deposition in the digestive tract was investigated. Amyloid was deposited first in the spleen, a little later in the digestive tract, and then in the liver and kidney. In the digestive tract, amyloid appeared simultaneously in the small and large intestine, and later in the glandular stomach. Amyloid deposition was most severe in the ileum, while it was not induced in the esophagus or non glandular stomach. Initially, amyloid deposition was observed along the small blood vessels and/or epithelial basement membranes in the lamina propria mucosa (LPM); it then extended to the stroma in the LPM. Amyloid deposition in each portion of the digestive tract had characteristic patterns in the LPM. Deposition of amyloid fibrils was confirmed by electron microscopy. The results suggest that the gastrointestinal biopsy used widely to diagnose human reactive amyloidosis is a sensitive early indicator of amyloidosis. PMID- 8199698 TI - Incidence and pathogenesis of villous tumors of the gallbladder, and their relation to cancer. AB - The aim of this study was to investigate the incidence and pathogenesis of villous tumors of the gallbladder, and their relation to cancer. Five hundred and thirty-three cases of cholecystectomy and 1300 randomly selected autopsy cases, mainly elderly individuals, were investigated. Gallbladders were fixed in 10% formalin after operation or at autopsy, followed by macroscopic study. In cases of villous tumors, the entire gallbladder was cut into 5-mm-thick serial sections, embedded in paraffin, cut to 4-microns, stained with hematoxylin and eosin (H&E), and histologically studied. To investigate cancer-associated antigens, i.e., carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19 9, deparaffinized sections were examined by the peroxidase-antiperoxidase (PAP) immunohistochemical technique with anti-CEA and anti-CA 19-9 antibodies. Villous tumor was found in two resected cases (0.38%) and in one autopsy case (0.08%). Histologically, one of the villous tumors consisted mainly of a proliferation of lining epithelia; the other two consisted mainly of a proliferation of glands. In all three cases, the patients had had accompanying chronic or acute inflammation and two were accompanied by cholecystolithiasis, which made us aware of the importance of inflammation or trauma from stones in the pathogenesis of such neoplasms. Although no apparent cancerous epithelium was observed in any of these tumors by studying H&E specimens, moderate structural and cellular atypism was found in one of them. The atypical epithelium in this case was positively stained for CEA and CA 19-9. It was concluded that villous tumor should be considered to be a premalignant lesion. PMID- 8199699 TI - A case of Crohn's disease limited to the appendix, showing a portentous ultrasonographic finding. AB - A case of Crohn's disease limited to the appendix is reported. A preoperative ultrasonic study of the lower right abdomen revealed an interesting appearance that we named the "milky way sign." Microscopic findings in the resected specimen confirmed that the sign represented adipose tissue of the mesoappendix that had become involved by transmural inflammation. This seems to be highly suggestive of Crohn's disease. PMID- 8199700 TI - Spontaneous passage of a colon cast in the absence of abdominal aneurysm. AB - The spontaneous passage of colon cast from a 76-year-old Japanese female patient is reported. Macroscopically, the colon case was shaped like the airbladder of a fish. Histopathologically, the cast consisted of degenerated colonal mucosa, including glands. No inflammatory reaction was apparent. The patient lacked any evidence of abdominal aneurysm. Since there have been only five reported cases of colon cast in the literature, and since in all of those association with abdominal aneurysms was always described, the present study represents the first report demonstrating the formation of a colon cast in the absence of associated abdominal aneurysm. However, the patient was found to exhibit several risk factors for ischemic colitis, such as arteriosclerosis on the wall of the abdominal aorta, chronic constipation, and colonic stenosis. Her colonal mucosal surface, indeed, suggested ischemic colitis. This case report, therefore, indicates that ischemic colitis, due to various causes, may be responsible for the formation of colon casts, and that the presence of an abdominal aneurysm is not necessarily a prerequisite for colon cast formation. This report may contribute to a better understanding of the pathogenesis of colon casts. PMID- 8199701 TI - Ulcerative colitis associated with Weber-Christian panniculitis and musculitis: a case report. AB - A case of 22-year-old man suffering from ulcerative colitis, in whom Weber Christian panniculitis and musculitis occurred simultaneously, is reported. He had suffered from ulcerative colitis for 7 years and he again had bloody stools 1 month before being admitted. Two weeks before admission, large (2-4 cm) subcutaneous tumors appeared. Weber-Christian panniculitis, musculitis, and active stage ulcerative colitis were diagnosed. All the symptoms went into remission after steroid therapy. The possibility of the existence of a common antigen in enterobacterial wall, colonic epithelium, and adipose tissue was suggested. PMID- 8199702 TI - A case of allergic liver injury induced by tegafur. AB - A 51-year-old woman constitutionally susceptible to allergy presented with acute allergic liver injury. She was taking tegafur for treatment of carcinoma of the uterus. The acute liver injury appeared 3 weeks after the first drug administration. She had marked elevation of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT), moderate jaundice, and eosinophilia. The virus markers revealed hepatitis B surface antigen (HBsAg) (-) antibody to hepatitis B surface antigen (HBsAb) (+), and immunoglobulin M HA antibody (IgM HA Ab) (-). The laparoscopic and histologic findings were compatible with drug-induced liver injury. Further, the results of the lymphocyte stimulation test (LST) and challenge test by tegafur were positive. From the above findings, the liver injury was diagnosed to be an allergic reaction induced by tegafur. The hepatic function returned to normal about 20 days after tegafur administration was suspended. Allergic liver injury induced by tegafur is very rare. We report the case with a short review of the literature. PMID- 8199703 TI - The effect of OP-2507, a prostacyclin analogue, on endotoxin-induced extensive hepatic necrosis in rats following partial hepatectomy. PMID- 8199704 TI - Plasma levels of mevalonate and 7 alpha-hydroxy-4-cholestene-3-one in cholesterol gallstone disease and their etiological significance. PMID- 8199706 TI - Structural features affecting chiral discrimination of terpene derivatives on a carbamated amylose stationary phase. AB - The chiral discrimination of enantiomeric derivatives of alpha-pinene was studied using amylose tris(3,5-dimethylphenylcarbamate) as a chromatographic stationary phase. The effect of structural features of these enantiomeric pairs on their chromatographic resolution was systematically studied to understand further the correlation between these features and chiral discrimination by the carbamated amylose. Structural analysis by molecular mechanics indicated that the conformation of the alpha-pinene skeleton was preserved with substitution in all its derivatives. However, in spite of the rigidity of the molecular backbone of these molecules, their resolution capabilities were different. Apparently, the site of the hydrogen-bonding substituents affected chiral discrimination by the stationary phase rather than conformational changes. Separation was achieved in spite of the fact that none of the members in the series had an aromatic moiety, and therefore pi-pi interactions with the stationary phase were insignificant. Hence it was concluded that the most important interaction of the terpene derivatives with the carbamated amylose was hydrogen bonding. PMID- 8199705 TI - Angiomyolipoma of the liver: a collective review. AB - This review summarizes the clinical and pathological findings of 52 cases of hepatic angiomyolipoma to discern and establish the most pertinent clinical and pathologic characteristics of the tumor. The disease was symptomatic in 60% of the patients. Abdominal pain or distress was the most common symptom, appearing in 37% of the patients, followed by malaise and upper abdominal mass or hepatomegaly. Of the 52 patients, only three (5.8%) showed associated tuberous sclerosis. Antemortem diagnosis of the tumor has been made with increasing frequency with the recent advent of computed tomography (CT) and ultrasound (US). The tumor was usually visualized as a hyperechoic mass by US imaging and as a low density mass less than -20 Housefield units by CT, and was hypervascular on angiography. The tumor was usually yellow to light tan, depending on the amount of fat tissue. Histologically, the tumor was characterized by an admixture of mature fat cells, blood vessels, and smooth muscle cells, with occasional foci of extramedullary hematopoiesis. The amount of smooth muscle component varied and often exhibited hypercellularity, pleomorphism with occasional bizarre giant cells, and moderate motitic activity. These features are considered conducive to an erroneous diagnosis of malignant tumor. However, since no malignant counterpart has been reported, it can easily be accurately differentiated histologically, if one is aware of the entity and can identify the three components of the tumor; blood vessels, smooth muscle cells, and fat. With regard to the histogenesis of angiomyolipoma, primitive mesenchymal cells around blood vessels may be the precursor cells. PMID- 8199707 TI - Structure elucidation of glykenin glycosidic antibiotics from Basidiomycetes sp. V. High-performance liquid chromatographic separation of components of glykenin. AB - The glycosidic antibiotics of the glykenin (GK) family produced by Basidiomycetes sp. were separated into nine components (GK-I-VII and DG) by normal-phase chromatography. It was found that these components differ in the number and location of the acetyl groups in the sugar moiety. Each component (GK-I-VII and DG) was further separated into three isomers (A, B and C), which possess different aglycones, by reversed-phase chromatography on an ODS column with methanol-acetonitrile as eluent. The best composition of the eluent was found to be methanol-acetonitrile-1% trifluoroacetic acid (4:3.5:2.5). The profile analysis of GK-III-VII and DG was also carried out using a modified mobile phase. The combination of normal- and reversed-phase chromatography separated all components of the GK mixture except GK-I and II. The relationship between structure and separation behaviour of GK is discussed. PMID- 8199708 TI - Isolation of hydrophobic lipoproteins in organic solvents by pressure-assisted capillary electrophoresis for subsequent mass spectrometric characterization. AB - Two capillary electrophoretic (CE) separation techniques with either simultaneous solvent flow induced by hydrostatic pressure or CE followed by low pressurization with helium were developed for the analysis of extremely hydrophobic proteins, such as the lung surfactant protein SP-C. For both related procedures, buffer solutions containing up to 70% of 2-propanol were used for the capillary electrophoretic separation. This high concentration of organic co-solvent, needed to solubilize the protein, dramatically reduces the electroosmotic flow (EOF) in aminopropyltrimethoxysilane-treated fused-silica capillaries. Because the EOF was insufficient to elute the separated analytes from the capillary, two "pressure assisted" CE techniques were developed. An additional flow to elute the separated analytes was produced either by raising the inlet of the capillary or by helium pressure. Using the pressurization procedure a baseline separation of the SP-C protein and its dimeric complex was obtained in a 55-minute electrophoretic run, followed by pressure elution of the analyte to the detector. The present combination of pressurization and capillary electrophoresis does not require any detergents or involatile buffer additives, which are usually needed to solubilize extremely hydrophobic lipoproteins. It is therefore applicable to on-line coupling with electrospray mass spectrometry for the direct structural characterization of hydrophobic proteins. PMID- 8199709 TI - Determination of aldicarb, aldicarb sulfoxide and aldicarb sulfone in tobacco using high-performance liquid chromatography with dual post-column reaction and fluorescence detection. AB - A screening method for the determination of aldicarb (AS) and its sulfoxide (ASX) and sulfone (ASN) metabolites in tobacco at low ppm levels is described. Tobacco samples are extracted using methanol with the aid of sonication at ambient conditions. The extract is filtered and then injected into a high-performance liquid chromatograph equipped with a dual post-column reaction system and a fluorescence detector. Chromatographic separation is performed on a C18 column with a mixture of methanol-acetonitrile-water containing 0.1% of triethanolamine as the mobile phase. Triethanolamine is added to improve peak shape of AS residues and to reduce the undesired interaction between residual silanols and interferences, mainly amino acids and other amines. The average recoveries for AS residues spiked in tobacco are higher than 95% for AS, 91% for ASN and 85% for ASX at levels of 0.5-10 ppm (w/w). The detection limit is 0.5 ppm for each of the target compounds. PMID- 8199710 TI - Elevated plasma adrenaline in spontaneously hypertensive rats. AB - Having found that circulating adrenaline (AD) is selectively elevated in stroke prone spontaneously hypertensive rats (SHRSP) compared with Wistar-Kyoto rats (WKY), we extended the comparison to include other normotensive and hypertensive rat strains. Aortic catheters were implanted in young (5-7 weeks) and old (7-9 months) WKY, Black-Hooded Wistar (BHW), Sprague Dawley (SD), spontaneously hypertensive rats (SHR) and SHRSP for repeated measurement of mean arterial pressure (MAP) and blood sampling under conscious resting conditions. In the young SHR and SHRSP, MAP was already significantly higher than in age-matched WKY but MAP in the SD rats was similar. Plasma AD was significantly higher in SHR and lower in SD rats when compared with WKY. There was no difference in plasma noradrenaline (NA) between strains at this age. At the older age, MAP was 40-60 mmHg higher in SHR and SHRSP than in WKY and BHW but was significantly lower in the SD strain. Circulating AD did not differ between the normotensive strains but was 3-4 times higher in the hypertensive strains. Plasma NA was elevated in SHR only. The acute reduction of MAP caused by ganglion blockade (an index of the sympathetically mediated component of resting blood pressure) was greater in SHR and SHRSP than in WKY at the older age only. However, the residual MAP after ganglion blockade was significantly higher in the hypertensive strains at both ages. Regression analysis showed that in the older rats, plasma AD was correlated with resting MAP, the reduction in MAP with ganglion blockade, the residual MAP and plasma NA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199711 TI - Lack of influence of circulating adrenaline on blood pressure in normotensive and hypertensive rats. AB - The relationship between circulating adrenaline and blood pressure was examined by manipulating plasma adrenaline levels in both normotensive and hypertensive rats: bilateral adrenalmedullectomy was performed in spontaneously hypertensive rats and stroke-prone spontaneously hypertensive rats; adrenaline bitartrate was infused chronically (25-32 micrograms/kg/h s.c.) into Wistar Kyoto, Sprague Dawley and stroke-prone rats via osmotic minipumps. Arterial and venous catheters were subsequently implanted for direct measurement of mean arterial pressure, blood sampling and drug administration in conscious rats. Adrenaline infusion for 5-6 weeks in Wistar Kyoto rats did not affect resting blood pressure (118 +/- 3 versus 119 +/- 1 mmHg in controls) even though plasma adrenaline was elevated 12 fold. Plasma noradrenaline was marginally elevated. Blood pressure was also unaffected by adrenaline infusion in Sprague Dawley or stroke-prone hypertensive rats. One week after adrenal medullectomy, plasma adrenaline was reduced 89% in spontaneously hypertensive rats, but blood pressure was unaffected. Ten weeks after adrenal medullectomy in young stroke-prone rats, resting blood pressure was slightly higher (167 +/- 2 mmHg) than in control rats (157 +/- 2 mmHg), although adrenaline was reduced by 34% in plasma and 67% in adrenal glands. Nitroprusside was infused acutely to lower blood pressure and reflexly elevate plasma noradrenaline. Neither of these responses were affected by chronic adrenaline infusion or adrenal medullectomy. In both adrenaline-infused Wistar Kyoto and medullectomised stroke-prone rats, autonomic blockade reduced blood pressure to a similar extent as in controls, indicating that the degree of sympathetic vasoconstriction was not altered by either treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199713 TI - Renal and cardiovascular effects of renal medullary damage with bromoethylamine in dogs. AB - Bromoethylamine (BEA, 30-40 mg/kg) was administered to dogs to determine whether damage to the inner medulla of the kidney, the putative source of a depressor hormone, causes hypertension in this species. Bromoethylamine produces hypertension in rats but this has not been confirmed in other species, although we have shown that this dose of BEA in dogs abolishes the release of a reno medullary vasodepressor hormone in response to marked increases in renal perfusion pressure. During acute BEA administration over 1 h to conscious dogs, there were no significant effects on renal blood flow, arterial pressure or total peripheral resistance, but there was a significantly greater diuresis compared to vehicle administration. Over the first 10-14 days after BEA, daily urine output rose 5-10 fold initially and plasma creatinine concentration rose markedly. There was no significant effect on arterial pressure, cardiac output, total peripheral resistance, or renal blood flow over this period. BEA administration caused extensive damage to the thin limbs of the loops of Henle, widespread thrombosis of blood vessels and haemorrhage into the interstitium of the dog renal medulla. Reno-medullary interstitial cells were devoid of lipid droplets, were synthetic, and were associated with increased amounts of extracellular matrix. Thus extensive renal medullary damage by BEA administration to conscious dogs did not alter resting systemic haemodynamics, and these results therefore provide no evidence for a role for the medulla in the maintenance of resting arterial pressure in the dog. PMID- 8199712 TI - Dietary fish oil administration retards blood pressure development and influences vascular properties in the spontaneously hypertensive rat (SHR) but not in the stroke prone-spontaneously hypertensive rat (SHR-SP). AB - In the present study, we compared the blood pressure in the SHR-SP and in the spontaneously hypertensive rat (SHR) after dietary administration of fish oil from 4 to 17 weeks of age. The retarding influence of dietary fish oils on the development of hypertension was prominent in the SHR (26 mmHg) and not evident in the SHR-SP (8 mmHg). The enhanced development of blood pressure in both the SHR and the SHR-SP is characterised by an elevated maximum contraction in the mesenteric vascular bed to sympathetic nerve stimulation and to injected noradrenaline. In SHR, but not SHR-SP, this maximum contraction was significantly attenuated by dietary fish oil. Likewise, acetylcholine mediated relaxation of the isolated aorta was enhanced in preparations from the SHR but not the SHR-SP. These physiological changes were also associated with a change in the total n-3 polyunsaturated fatty acids (PUFAs) content in vascular tissue, which were inversely proportional to the prevailing blood pressure values seen in all three strains of rat receiving dietary fish oils. Platelet activated thromboxane production was equally depressed in WKY (Wistar Kyoto), SHR and SHR-SP rats. The results indicate that the blood pressure lowering effect of fish oil when administered during the period of development of hypertension is much greater in the SHR than it is in the SHR-SP. Furthermore the lowering of blood pressure by fish oil administration is related to a restoration of normal vascular contraction and normal vascular relaxation, but not related to a suppression of serum thromboxane production. PMID- 8199714 TI - Vasopressin and a nonpeptide antidiuretic hormone receptor antagonist (OPC 31260). AB - The development of nonpeptide orally active AVP analogues has provided a new tool with which to assess the physiological and pathophysiological role of vasopressin (AVP). We have previously characterised the nonpeptide vasopressin V1 receptor antagonist OPC-21268, and now report the in vitro characterisation of the nonpeptide V2 receptor antagonist OPC-31260 in the rat. OPC-31260 caused a concentration-dependent displacement of the selective AVP V2 receptor antagonist radioligand, [3H]desGly-NH2(9)[d(CH2)5, D-Ile2,Ile4]AVP from V2 receptors in rat kidney medulla membranes. The concentration of OPC-31260 that displaced 50% of specific AVP binding (IC50) was 20 +/- 2 nmol/l for renal V2 receptors. OPC-31260 also caused a concentration-dependent displacement of the selective AVP V1 receptor antagonist radioligand, [125I]-[d(CH2)5,sarcosine7]AVP from V1 receptors in both rat liver and kidney medulla membranes. The IC50 was 500 +/- 30 nmol/l for both renal and liver V1 receptors. After oral administration to rats, OPC 31260 was an effective inhibitor of AVP at renal V2 and liver V1 receptors in a time-dependent manner. In vitro binding kinetic studies showed that OPC-31260 was a competitive antagonist at both the renal V2 receptor and the hepatic V1 receptor. OPC-31260 is a nonpeptide, orally effective competitive inhibitor of AVP with a V2:V1 receptor selectivity ratio of 25:1 indicating relative V2 receptor selectivity. PMID- 8199715 TI - Hypertension in pregnancy. AB - From the clinical point of view proteinuric hypertension or preeclampsia is the most important form of hypertension in pregnancy and carries the greatest risks for mother and foetus. The syndrome 'preeclampsia' differs from other types of hypertension and its effects on mother and foetus are not clearly benefited by lowering the blood pressure with drugs. The characteristic morphological changes and altered vascular reactivity which develop in preeclampsia commence at about 14 weeks gestation, long before hypertension or proteinuria appear. Many abnormalities in coagulation mechanisms appear in preeclampsia and some may play an important part in pathogenesis. Increased plasminogen activator inhibitor may play a key role. Antihypertensive drugs used during pregnancy may reduce foetal mortality and the incidence of preeclampsia. Calcium supplementation and aspirin may reduce the incidence of preeclampsia in high risk subjects. Heparin and dipyridamole may reduce the risk of preeclampsia in high risk patients with renal disease. PMID- 8199716 TI - Studies on the mechanisms of glucocorticoid hypertension in humans. AB - Hypertension is a common feature of both Cushing's syndrome, which is relatively rare, and iatrogenic steroid administration, which is much more common. Cardiovascular mortality and morbidity are very significant in patients with both naturally occurring and iatrogenic disease. The mechanism of glucocorticoid induced hypertension in man remains undefined. Contrary to previous notions, it does not reflect urinary sodium retention or volume expansion. Increased pressor responsiveness may be an important contributor to the rise in blood pressure. PMID- 8199717 TI - Arterial haemodynamics and ventricular-vascular interaction in hypertension. AB - Comprehensive studies of arterial pressure require understanding of the whole pressure waveform, not just the extremes of pressure (systolic and diastolic) in a peripheral artery. Such studies have been conducted in Sydney from the early 1960s and have been based on the concepts of steady state analysis, of vascular impedance, and of transfer function for pressure and flow in the frequency domain. These studies have emphasised the importance of wave reflection and have identified the cause of wave reflection, and shown how wave reflection can be modified. In the elderly and hypertensive, wave reflection returns early from peripheral sites, as a consequence of arterial stiffening, and boosts systolic pressure in the ascending aorta; this is responsible for "isolated systolic hypertension". Wave reflection in the upper limb causes the ill effects of arterial stiffening and the beneficial effects of vasodilator drugs to be underestimated. A new process, which combines the old technique of sphygmography with conventional sphygmomanometry, enables more precise evaluation of hypertensive subjects. Abnormal (early) wave reflection is a particular disadvantage in the presence of myocardial hypertrophy and impairment, and can explain development of cardiac failure. These concepts explain the favorable therapeutic effects of vasodilator drugs as being a consequence of reduction in wave reflection, as well as resulting from reduced peripheral resistance. PMID- 8199718 TI - Plasma and urinary endothelin 1, prostacyclin metabolites and platelet consumption in pre-eclampsia and essential hypertensive pregnancy. AB - This study examined plasma and urinary endothelin 1 and urinary metabolites of prostacyclin and thromboxane, in women with pre-eclampsia and age and gestation matched controls. To determine if changes in endothelin 1 and urinary prostanoids in pre-eclampsia were due to hypertension per se, a comparison was made to a group of age and gestation matched pregnant uncomplicated essential hypertensive women. Measurements were taken prior to delivery, and at 6 weeks and 6 months post-partum, and were compared to a group of age matched non-pregnant controls. Plasma endothelin 1 was significantly elevated and the urinary metabolite of prostacyclin (2,3-dinor-6-keto-PGF1 alpha) was significantly suppressed in pre eclamptic pregnancy, compared to normal pregnancy and essential hypertensive pregnancy. As the level of blood pressure was similar in the pre-eclamptic and essential hypertensive groups, these changes are not due to an increase in blood pressure per se. Urinary endothelin 1 was not different in the 3 pregnant groups prior to delivery but fell significantly after delivery. Urinary endothelin 1 was significantly lower in the essential hypertensive group at 6 weeks post-partum compared to pregnant controls with a similar trend at 6 months. Urinary 11 dehydro-TXB2 was elevated in pregnancy, but no further elevation was seen in women with pre-eclampsia. Platelet counts were lower, and circulating neutrophil counts higher in pre-eclampsia prior to delivery. A combination of increased plasma endothelin 1 and reduced tissue prostacyclin synthesis may contribute to hypertension, placental insufficiency, foetal growth retardation and renal dysfunction in pre-eclampsia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199719 TI - The National Consensus Conference--not always what it seems. PMID- 8199720 TI - Relationship between chemosensitivity, obesity and blood pressure in obstructive sleep apnoea. AB - It has previously been documented that patients with obstructive sleep apnoea (OSA) have an abnormal blood pressure (pressor) response to acute hypoxia when awake. The relationship between hypoxic chemosensitivity and 24 h blood pressure in OSA is not known. Twenty-four hour ambulatory BP (ABP) was measured at 15 min intervals for 24 h using a non-invasive device (Oxford Medilog ABP or Spacelabs 90207 recorder) in 49 men (mean age 51 +/- 9 years), with OSA. The BP response to acute hypoxia was measured either directly (radial arterial line) or indirectly (Finapress) during wakefulness. The pressor response to hypoxia (expressed as the slope of the regression line of mean BP on % fall in arterial oxygen saturation) was compared with the results of the ABP recording, sleep study data and clinical variables. A pressor response to acute hypoxia was present in all patients (mean 1.4 +/- 1.1 mmHg/% delta SaO2, range 0.1-4.5). There was a relationship between the magnitude of the pressor response to hypoxia, severity of sleep apnoea (RDI and minimum SaO2) and central obesity (waist measurement). In contrast, there was no relationship between BP response to hypoxia during wakefulness and 24-h BP. However, increasing obesity and severity of OSA were associated with loss of the normal fall in BP at night. We conclude that enhanced chemosensitivity is common in OSA but there is no demonstrable link between chemosensitivity and mean daytime or night-time ABP. PMID- 8199721 TI - Some thoughts on pathogenesis, therapy and prevention of hypertension. PMID- 8199722 TI - The relationship between salivary growth factors, electrolytes and abnormal sodium transport in human hypertension. AB - We have previously shown cheek cell Na+/H+ antiporter activity to be reduced in human hypertensives. We have now examined the relationship between abnormal antiporter activity and a variety of salivary factors. Total protein concentration and amylase activity were higher in hypertensives, but salivary flow rate and epidermal growth factor, transforming growth factor-alpha, calcium, and magnesium concentrations were not significantly different between hypertensives and normotensives. The lowered cheek cell Na+/H+ antiporter activity in those hypertensives with diastolic BP greater than 95 mmHg was accompanied by lowered salivary Na+/H+ ratios. In borderline hypertensives (diastolic BP between 90 and 95 mmHg), the Na+/H+ ratio was reduced to a similar extent to that seen in those hypertensives with a diastolic BP above 95 mmHg, however the cheek cell antiporter activity was not reduced, suggesting that these two differences are not related in a simple fashion in all hypertensives. It is concluded that it is unlikely that differences in salivary growth factors explain the lowered cheek cell Na+/H+ antiporter activity observed in human hypertension. Our findings indicate that salivary electrolyte composition may be related to cheek cell Na+/H+ antiporter activity and these parameters may be altered in hypertension. PMID- 8199723 TI - Felodipine, metoprolol and their combination compared with placebo in isolated systolic hypertension in the elderly. AB - This study compared with placebo the efficacy and tolerability of optimised doses of felodipine 5-20 mg daily, metoprolol 50-200 mg daily and their combination in subjects 60 years or over with isolated systolic hypertension. The study employed a randomised double-blind crossover design with allocation of treatment order within subjects by Latin squares. For each subject, after a single-blind run-in placebo phase, there were four randomised treatment phases each of six weeks duration, with a dose titration step at three weeks if necessary. Twenty-eight subjects entered the randomised phases of the study and twenty-one completed all four phases--13 male, 8 female (ages: median 71, range 59-85 years). At the end of both the felodipine and metoprolol phases systolic and diastolic pressure were reduced at 2 hours postdose compared with the placebo phase (p < 0.001), the blood pressure reduction with felodipine (-40/-20 mmHg) being greater than that with metoprolol (-15/-9 mmHg) (p < 0.01). Immediately predose (12 hours postdose) there was a persisting reduction of supine systolic blood pressure (-17 mmHg) with felodipine (p < 0.001), but there was no significant effect of metoprolol. At both measurement times the two drugs when in combination had an additive effect on blood pressure. There was a 20% increase in reported symptoms during each of the active treatment phases. Four subjects withdrew during the randomised phases because of probable drug-related adverse events and six subjects required dosage reductions during the felodipine or combination phases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199724 TI - Mono- and combination therapy with felodipine or enalapril in elderly patients with systolic hypertension. AB - Using a randomised double-blind crossover design with Latin square allocation of treatments in 20 subjects (7 male, 13 female-ages: 61-87 years) with systolic hypertension, we investigated the efficacy and tolerability of once daily felodipine (extended release) 5-20 mg, enalapril 5-20 mg and their combination compared with placebo in four treatment phases each of 6 weeks duration. During each phase, doses were titrated to achieve a predose clinic supine systolic blood pressure of 140 mmHg or to a predetermined maximum dose. In both the felodipine and combination phases, predose supine and standing systolic and diastolic pressures were significantly reduced compared with the placebo phase (decrease in supine pressure: -13/-5 and -18/-7, respectively). Only predose supine diastolic pressure was significantly reduced (-3 mmHg) compared to placebo in the enalapril phase. In combination the effects of the two drugs on predose blood pressure were additive. There was a 40-60% increase in reported symptoms in the felodipine and combination phases compared with the placebo and enalapril phases. Thus, in elderly subjects with systolic hypertension, felodipine effectively reduces blood pressure throughout the dose interval but with vasodilator adverse effects. In contrast, enalapril is well tolerated but is less effective in reducing blood pressure throughout the whole dose interval. PMID- 8199726 TI - Vestibular bibliography. PMID- 8199725 TI - The effect of captopril treatment and its withdrawal on the gene expression of the renin-angiotensin system. AB - The mRNA expression of renin, angiotensinogen and angiotensin converting enzyme (ACE) was determined in the kidneys and livers from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) during chronic treatment with captopril and following its withdrawal. Chronic captopril treatment was associated with a dramatic rise in renin mRNA in the kidney and an elevation in mRNA for ACE in the liver. The release from captopril treatment was associated with a reversal of the increase in kidney renin mRNA but no reversal of the sustained elevation of ACE mRNA in the liver. In situ hybridisation revealed a localisation of renin to the area of the juxtaglomerular apparatus in the kidneys from untreated animals, but recruitment of vascular sites of renin expression in kidneys from captopril treated animals. In kidneys from released animals, renin mRNA expression was once again confined to the juxtaglomerular apparatus. ACE mRNA was expressed in hepatocytes throughout the livers from animals in all treatment groups. The results highlight a differential effect of captopril withdrawal upon the gene expression of the components of the renin-angiotensin system in kidney and liver. PMID- 8199727 TI - Central vestibular, vestibulo-acoustic and oculomotor dysfunction in hereditary disorders. A review of the literature and a report on some additional findings. PMID- 8199728 TI - Theoretical mechanical frequency response of the otolithic organs. AB - A distributed parameter model, which consisted of three coupled partial differential equations, describing the mechanical response of the otolithic organs, was used to develop a system mechanical transfer function. The equations were Laplace transformed and combined to yield a transfer function for otoconial layer displacement relative to an acceleration stimulus. Acceleration is either skull acceleration or gravity. In addition, transfer functions for the gel layer and endolymph fluid layer were also developed which included a spatial coordinate as a transfer function variable. Frequency response diagrams were constructed from the transfer functions, using numerical values of nondimensional parameters developed in an earlier study. The otoconial layer transfer function was compared to physiologic data on utricular primary afferent neurons and there was good agreement except at low frequencies. The discrepancy between the theoretical transfer function and the primary afferent response can be attributed to contributions of the spike encoder, which has been measured experimentally, additional non-mechanical components in the transduction process, and even non linear elements in the mechanical system. PMID- 8199729 TI - Postural instability on one foot in patients with loss of unilateral peripheral vestibular function. AB - The vestibular system is a major contributor to postural control and the vestibular nuclei are closely connected to the limb spinal motor neurons. Acute loss of unilateral peripheral vestibular function results in, among others, postural instability which improves with time due to central compensatory processes. It has been shown, however, that a number of processes, such as sensorimotor restriction, drugs, and so forth, may affect the speed and the quality of compensation. Due to the difference of ipsilateral vs contralateral connectivity between the vestibular nuclei and the limb spinal motor neurons, and the peculiarities of compensatory processes, the ipsilateral may not compensate as well as the contralateral foot to lesion in patients who lost unilateral peripheral vestibular function. To explore this possibility, the sway, while standing on each foot, was recorded in normal subjects (N = 30) and compensated (except three) patients (N = 37) with loss of unilateral peripheral vestibular function and the percentage difference between the two sways was calculated. No difference was found between patients swaying more on the ipsilateral vs patients swaying more on the contralateral foot to lesion (p > .80). There was, however, a statistical difference between patients as a group vs normal subjects as a group (p = .005). These data suggest, although not evident in all patients of the group, that sway on the contralateral foot was less than the sway on the ipsilateral foot to lesion, as initially speculated. They may, however, signify that one foot compensates better than the other. This is a preliminary report and more testing is on-going to confirm these results. PMID- 8199730 TI - Visually induced vertical self-motion sensation is altered in microgravity adaptation. AB - Vertical vection is a phenomenon of self-motion perception in immobile subjects, which is conventionally perceived in the opposite direction of the upward or downward moving visual stimulus. The Austrian scientific cosmonaut experienced reversed vertical vection from sinusoidal stimulation on third and sixth day of space flight as well as immediately postflight. The occurrence of short periods of reversed vection from constant velocity stimulation six months postflight can be interpreted as a reactivation of an "alternative" visual processing mode. This may indicate that microgravity modulations of the neuronal pathways which process visual information for dynamic orientation are not completely extinguished in the processes involved in readaptation to 1-G. PMID- 8199731 TI - Peripheral vestibular and vestibulo-cochlear dysfunction in hereditary disorders. A review of the literature and a report on some additional findings. PMID- 8199732 TI - Cellularity of atherosclerotic lesions. PMID- 8199733 TI - Monocyte adhesion and transmigration in atherosclerosis. PMID- 8199734 TI - Cellular mechanisms for the oxidative modification of lipoproteins: implications for atherogenesis. PMID- 8199735 TI - Immune mechanisms in atherosclerosis. PMID- 8199736 TI - Thrombotic mechanisms in atherosclerosis. PMID- 8199737 TI - The place of ferritin among risk factors associated with coronary artery disease. AB - BACKGROUND: Prospective studies of East Finnish men demonstrated an increased risk of myocardial infarction in association with elevated serum ferritin levels (> or = 200 micrograms/l). The present study was designed to explore whether serum ferritin concentrations are related to angiographically determined coronary artery disease or to a past history of myocardial infarction. METHODS: We studied 225 men and 74 women, most of them of French-Canadian origin, undergoing elective coronary arteriography, and classified them according to the presence, absence, and severity of angiographic findings. A history of myocardial infarction was defined as clinical and electrocardiographic and/or enzymatic evidence of a myocardial infarction occurring more than 12 weeks previously or akinesia of the left ventricle. Serum ferritin was measured with the Baxter Stratus II immunoassay system. RESULTS: There were no significant differences in ferritin levels between patients with > or = 50% diameter stenosis (195 men, 48 women) and those with intact or minimally affected arteries (31 men, 26 women) either in men or in women. There was no correlation between the quartiles of serum ferritin and the severity of coronary artery disease. There were no differences in ferritin levels in patients with (95 men, 25 women) or without (71 men, 43 women) a history of myocardial infarction. However, serum lipid levels were significantly related to all the above conditions. CONCLUSION: In a French-Canadian population, serum ferritin levels, unlike serum lipids, were not related to the presence or severity of angiographically determined coronary artery disease, nor to a history of myocardial infarction. PMID- 8199738 TI - Residual left ventricular pump function following acute myocardial infarction in postmenopausal diabetic women. AB - BACKGROUND: The Framingham Study indicated that women with diabetes mellitus developed cardiac failure four times more often than those without diabetes mellitus after acute myocardial infarction. However, there is little information on residual left ventricular pump function after myocardial infarction in female diabetic patients. METHODS: To evaluate the difference between postmenopausal women and age-matched men in the impact of diabetes mellitus on left ventricular pump function during the first year after myocardial infarction, radionuclide angiography was performed during the third week after acute myocardial infarction and again 1 year later in 50 patients (21 women, 29 men) with diabetes mellitus and 62 patients (25 women, 37 men) without diabetes mellitus. RESULTS: Although the radionuclide angiographic indices did not change during the first year after myocardial infarction in non-diabetic patients, left ventricular end-diastolic volume increased, and the left ventricular ejection fraction, the regional ejection fraction of the non-infarcted area, and the ratio of arterial systolic blood pressure to left ventricular end-systolic volume (pressure:volume ratio) decreased in the diabetic patients. Furthermore, the degree of change in the left ventricular end-diastolic volume, the left ventricular ejection fraction, the regional ejection fraction of the non-infarcted area, and the pressure:volume ratio in diabetic women was larger than that in diabetic men. CONCLUSION: The increase in the left ventricular end-diastolic volume and the decrease in the regional ejection fraction of the non-infarcted area during the first year after myocardial infarction in postmenopausal women with diabetes mellitus indicate that female sex associated with diabetes mellitus may be important factors in left ventricular remodeling in postmenopausal women. PMID- 8199739 TI - Late potentials during left ventricular healing of acute myocardial infarction. AB - BACKGROUND: Late potentials and left ventricular remodeling are important factors in the prognosis of acute myocardial infarction. However, the relationship between late potentials and ventricular remodelling has not been fully evaluated. METHODS: We evaluated clinical characteristics, coronary angiographic findings and radionuclide angiographic measures about 1 month after an acute myocardial infarction in patients with and without late potentials. RESULTS: Although the left ventricular ejection fraction of patients with late potentials was not different from that of patients without late potentials, the left ventricular end diastolic volume of patients with late potentials was larger than that of patients without late potentials (P < 0.05). There was a significant positive correlation between the left ventricular end-diastolic volume and the filtered QRS duration (r = 0.53, P < 0.001). The root mean square of the voltage in the terminal 40 ms and the low-amplitude signal duration of < 40 microV in the terminal QRS sequence were also correlated with the left ventricular end diastolic volume (r = 0.40, P < 0.02, and r = 0.39, P < 0.02, respectively). Patency of the infarct-related vessel in the late phase of an acute myocardial infarction was an important factor associated with the occurrence of late potentials (P < 0.01). CONCLUSION: A larger left ventricular end-diastolic volume in patients with late potentials might be associated with left ventricular remodeling during the first month after an acute myocardial infarction. PMID- 8199740 TI - Gliding-window fast Fourier transform analysis of the entire QRS complex and the distribution of area ratio peaks in healthy subjects and patients with myocardial infarction. AB - BACKGROUND: The high-frequency contribution (i.e. 60-120 Hz) within the QRS complex of the surface ECG is supposed to be related to the arrhythmogenic substrate underlying sustained ventricular tachycardia in patients with coronary artery disease. One of the factors that prevents a wider clinical application of spectral analysis based on the fast Fourier transform is the considerable intra individual variability of its results. This study presents a novel alternative approach of frequency-domain analysis, aimed at minimizing this methodological drawback. METHODS: The proposed method uses gliding-window fast Fourier transform analysis of the signal-averaged ECG to provide values expressing the area ratio for two predefined frequency ranges (60-120 Hz divided by 0-120 Hz). The term gliding window is derived from the methodological principle by which the window analyzed is moved from the onset of the QRS complex into the ST segment. Values of area ratios obtained for every time instant of the interval of gliding are the basis for construction of curves. These are further analyzed in order to find patterns that characterize abnormal ventricular activation, with special emphasis on the identification of arrhythmogenic correlates. RESULTS: In a group of 30 healthy subjects, the distribution of area ratio peaks was characterized according to their value and timing. The distribution of area ratio peaks in 43 patients with myocardial infarction differed substantially from the normal distribution in the control group. The amplitude of the peaks and their timing was not related to the occurrence of late ventricular potentials. CONCLUSION: The method of gliding-window fast Fourier transform analysis eliminates the variability of results obtained by traditional spectral analysis of the ECG signal. A higher number and a different distribution of high-frequency peaks during the QRS complex in postmyocardial infarction patients reflect abnormal ventricular activation. However, late ventricular potentials are not related to a higher proportion of high frequencies in the corresponding time interval within the terminal QRS complex. PMID- 8199741 TI - Variable and circadian response to a fixed high-dose (12 500 IU twice daily) subcutaneous heparin regimen after thrombolytic therapy for acute myocardial infarction. AB - AIM: To determine the effect of a fixed high-dose (12 500 IU twice daily) subcutaneous heparin regimen on coagulation parameters after thrombolysis with streptokinase. BACKGROUND AND METHODS: A number of large thrombolytic trials have allocated patients to fixed high-dose (12 500 IU twice daily) subcutaneous heparin with no monitoring of coagulation parameters. We hypothesized that heparin's apparent lack of benefit and increased haemorrhagic complications in these trials may be the result of inappropriate anticoagulation. We therefore studied 11 patients who received intravenous streptokinase and oral aspirin for acute myocardial infarction and were subsequently started on the above heparin regimen. Blood samples were taken for activated partial thromboplastin time (APTT) and thrombin time before streptokinase and then immediately before and 6 h after each heparin injection on days 1,4, and 6, and 3 and 6 h after streptokinase on day 5. Plasma heparin levels were also measured on all post streptokinase samples. Plasma fibrinogen was measured before the administration of streptokinase and once daily on the other sampling days. RESULTS: Both the median APTT and thrombin time were prolonged above the normal range throughout day 1, when fibrinogen levels were depressed, with a non-significant variation between the sampling points. By day 4, however, when fibrinogen levels had returned to pre-streptokinase levels, the median (range) APTTs at 8 a.m. and 8 p.m. (pre-heparin) were similar, and below the therapeutic range, at 52 (38-76) and 48 (39-79) s (NS). Six hours after each heparin injection the APTTs were elevated, but the median (range) 2 p.m. peak of 63 (46-138) s was lower than that at 2 a.m., 125 (58-178) s (P = 0.003). A similar peak and trough, and apparent circadian, APTT response pattern was seen on days 5 and 6. The thrombin time showed the same variation, which was also mirrored in the plasma heparin levels, although the circadian effect was not as marked. CONCLUSION: There is a marked individual variation in response to fixed-dose (12 500 IU twice daily) subcutaneous heparin, with many patients inadequately anticoagulated and an obvious circadian pattern of response. These findings have important implications when considering the benefits and haemorrhagic complications of subcutaneous heparin therapy in general and following thrombolysis in particular. PMID- 8199743 TI - Bibliography of the current world literature. PMID- 8199742 TI - The effect of platelet-activating-factor antagonist TCV-309 on arrhythmias and functional recovery during myocardial reperfusion. AB - BACKGROUND: We investigated the effects of a platelet-activating-factor antagonist TCV-309, an antagonist of metabolites of ischemia, on arrhythmias and functional recovery during in-situ reperfusion in dogs. METHODS: Open-chest anesthetized dogs were subjected to ligation of the left anterior coronary artery. Ischemia was maintained for 20 min after which reperfusion was allowed. A cardiac surface ECG was recorded continuously with the II limb lead. Monophasic action potential, left ventricular segment shortening measured by sonomicrometer, and left ventricular pressure were recorded simultaneously under atrial pacing (group A, n = 14). In a second group of dogs, TCV-309 (1 mg/kg) was administered before coronary artery occlusion (group B, n = 12). The hearts were constantly paced through the right atrium at 120 beats/min throughout all experiments. Measurements were continuously obtained from before drug administration to 30 min after reperfusion. RESULTS: The 90% repolarization time of monophasic action potentials in group B revealed significant recovery compared with group A until the fifth minute after reperfusion (P < 0.02). Reduction of severe ventricular arrhythmias was observed during reperfusion in group B (P < 0.05). The percentage segment shortening and left ventricular pressure did not differ significantly between the groups. CONCLUSION: The platelet-activating-factor antagonist had beneficial effects on arrhythmias but not on functional recovery during reperfusion after brief coronary artery occlusion in situ in dogs. PMID- 8199744 TI - Advantages and limitations of metaanalytic regressions of clinical trials data. AB - OBJECTIVE: To focus on methodology of metaregression and demonstrate to clinicians, through 2 published examples, some strengths and limitations. EXAMPLE 1 METHODS: Metaanalysis of data from 20 years of randomized trials of lidocaine prophylaxis in preventing primary ventricular fibrillation (VF) in myocardial infarction used separate data for control and active-treatment groups to model the risk of VF as a function of year of publication and other study characteristics. EXAMPLE 1 RESULTS: Collinearity between pairs of predictor variables can lead to difficulty in interpreting logistic regression models. EXAMPLE 2 METHODS: Metaanalysis of data from 7 trials (323 patients) measured treatment effect of immunosuppressive therapy for acute Crohn's disease by response-rate difference (RD, experimental minus control group). EXAMPLE 2 RESULTS: Weighted least-squares regression models of the RD suggested an association between RD and various study characteristics, but collinearity again led to difficulty in interpretation of multiple regression results. DISCUSSION: Warning signs of colinearity include: large pairwise correlations between predictor variables, large changes in coefficients caused by the addition or deletion of other variables, and extremely large SEs for coefficients. Suggestions for coping with collinearity include: removing redundant variables from the model, reducing reliance on interpretation of coefficients for confounding variables, forming one or more summary variables, centering the data, collecting more data, and using more sophisticated regression methods. CONCLUSIONS: Metaanalysis can explore variations in as well as summarize results of randomized trials. Although metaregression has advantages, study characteristics are often strongly associated with each other, leading to collinearity. PMID- 8199745 TI - The effect of nonsteroidal agents (NSAIDs) on the pharmacokinetics and pharmacodynamics of metolazone. AB - NSAIDs attenuate the natriuretic response to loop diuretics. Their effect on the action of distal tubular diuretics is poorly explored. Accordingly, the pharmacokinetics and pharmacodynamics of metolazone [M], a distal tubular diuretic, with and without indomethacin [M+I] or sulindac [M+S] were examined in six healthy volunteers. Urine samples were obtained over 36 hours post-metolazone dosing for the determination of sodium, potassium and metolazone concentration. Though cumulative M excretion 750 +/- 247 [mucg/36 h] [M]; 749 +/- 239 [M+I]; 848 +/- 443 [M+S] was comparable between treatment groups, total sodium [Na+] excretion was significantly depressed in the presence of S or I, 685 +/- 114 [mEq/36 h] [M]; 454 +/- 90 [M+I] (p < or = 0.05); 553 +/- 123 [M+S] (p < or = 0.05). Peak Na+ excretion [muEq/min] was significantly decreased by I only and time to peak Na+ excretion did not differ amongst treatment groups. Total potassium [K+] excretion 160 +/- 39 [mEq/36 h] [M]; 111 +/- 53 [M+I] (p < or = 0.05); 135 +/- 31 [M+S] significantly decreased with I. This phenomenon was most evident between 12 and 36 hours. The administration of I or S with M significantly blunted sodium excretion on a purely pharmacodynamic basis while the decline in urinary potassium excretion upon addition of I to M related probably to an attenuation of braking phenomenon induced kaliuresis. These findings likely reflect NSAID-induced sodium reabsorption at loci prior to the site of action of metolazone. PMID- 8199746 TI - Enhancement of natural killer cell activity in septic shock patients by a mixture of the calcium ionophore A23187 and the phorbol ester TPA: in vitro studies. AB - Preincubation of peripheral blood lymphocytes from drug-free, healthy volunteers with a mixture of the calcium ionophore A23187 (Io) and the phorbol ester TPA (12 O-tetradecanoylphorbol-13-acetate) consistently resulted in a significant enhancement (dose-dependent; maximum immunostimulation obtained with the Io + TPA final mixture concentration of 10 uM + 250 ng/ml, respectively) of natural killer cell activity (NKCA) (n = 8; mean +/- SD of 16.8 +/- 8.9 and 52.0 +/- 18.0, paired Student's t-test p < 0.005; effector-to-target cell ratio of 30:1). Results from the same protocol, but using samples from septic shock patients followed a similar trend; however, and perhaps reflecting the significantly lower baseline NKCA in this group of individuals (n = 7), the mean value reached for this cellular immune function after incubation with Io + TPA was significantly lower than that of the treated controls' group (mean +/- SD of 19.8 +/- 11.6 and 52.0 +/- 18.0, respectively, Student's t-test p < 0.005). As expected from the role of calcium in the activation of NKCA, incubation with the Io significantly increased baseline NKCA, which was largely unchanged by TPA. Expression of the CD56+ and CD16+ phenotypes in septic shock patients did not correlate directly with NKCA, suggesting that this condition may be associated with changes in the function rather than the quantity of these cellular markers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199747 TI - Risk of infection from blood and blood products in the context of the AIDS scandal in Germany. PMID- 8199748 TI - Quality control of extemporaneously prepared microdose captopril capsules: weight variation versus content uniformity. AB - Microdose (1 mg) captopril therapy is commonly used for the initial dose titration in patients with congestive heart failure. Since this dosage form is not commercially available, it has to be extemporaneously compounded. Quality control of each batch is commonly evaluated using the weight variation technique described in the USP. Despite careful titration with microdose, captopril capsules variability in patient's response has been observed. In order to explain this fluctuation, the actual content of extemporaneously compounded microdose captopril capsules was evaluated using a high pressure liquid chromatographic assay. Microdose captopril capsules were prepared by triturating 25 mg tablets with lactose in a mortar using standard geometric dilution technique and a Sharpe Dohme hand-operated capsule filling machine. Forty-eight microdose captopril capsules were randomly selected from the compounded batch and were individually assayed for captopril amount. The mean +/- standard deviation (SD) amount of captopril in each capsule was 1.27 g +/- 0.31 mg with a range of 0.84 g to 1.96 mg. The coefficient of variation was 24.5%. Ten captopril capsules were randomly selected from the compounded batch and were individually weighed. The capsules had a mean weight +/- SD of 198.3 g +/- 21.2 mg and a coefficient of variation of 7.3%. Even though the extemporaneously prepared microdose captopril capsules were within acceptable limits for weight variation described in the USP, the actual dose administered to the patients could vary by as much as 24.5%. PMID- 8199749 TI - Sample size considerations for assessing individual bioequivalence based on the method of tolerance intervals. AB - This is the consideration of sample sizes for assessing individual bioequivalence based on the use of tolerance intervals. The sample size procedures discussed include a direct distribution-free method, indirect parametric method and a direct parametric method. Design considerations are discussed based on the results of the direct parametric method. Tables are provided for easy access of results. PMID- 8199750 TI - A prospective study for validation of Bayesian prediction approach to adjust individual lidocaine dosage. AB - A Bayesian approach, in which the estimates of the population pharmacokinetic parameters of lidocaine reported by Vozeh et al. [1984 a and b] and one measurement of serum lidocaine concentration as feedback information were utilized, was prospectively evaluated in 20 Japanese patients. The concentration of lidocaine in serum sampled from each patient at 1.5 to 3 hours after the commencement of i.v. lidocaine therapy was measured and the most likely pharmacokinetic parameters of that patient were predicted by the Bayesian program for microcomputer. Having the predicted parameters, we got the concentrations of lidocaine at 12 and 24 hours (C12 and C24) after starting the therapy within the recommended therapeutic range (2-5 micrograms/ml) by adjusting the individual dosage. As a result, the values of C12 and C24 remained within the therapeutic range in all patients and in all except one, respectively. The mean % prediction error (measured minus predicted concentration standardized by measured one) and its 95% confidence interval were 1.8% and -11.4 to 14.7% for C12, and -2.3% and 11.9 to 7.4% for C24, showing that the prediction of both C12 and C24 was not biased. The correlation coefficients between the measured and predicted concentrations were 0.574 for C12 and 0.721 for C24 (p < 0.01). From these findings, the present Bayesian method implemented with the estimates of pharmacokinetic parameters in a Swiss patient population is useful for sufficiently accurate and precise assessment of individual dosage requirement within a few hours after starting lidocaine therapy. PMID- 8199751 TI - Dose linearity of the pharmacokinetics of the new H+/K(+)-ATPase inhibitor pantoprazole after single intravenous administration. AB - Pantoprazole is a specific inhibitor of the H+/K(+)-ATPase of the gastric parietal cell. The dose-dependency of a range of pantoprazole pharmacokinetic characteristics was studied. Twelve healthy male subjects were given 10, 20, 40 and 80 mg pantoprazole intravenously according to a randomized, single blind, 4 period change-over scheme. The area under the concentration vs time curve (AUC) and the maximum serum concentration (Cmax) showed a linear increase in line with the dose. Apparent volume of distribution (Vd area), clearance (Cl) and terminal half-life (t1/2) were independent of the dose. The dose-independent elimination of pantoprazole was attributed to the lack of interaction of the drug with cytochrome P450. In clinical practice, a good predictable response, as well as a low potential for interaction with other drugs might be expected. PMID- 8199753 TI - Cocaine abuse and reproduction. AB - Cocaine abuse today is widespread and is on the increase in North America. It is estimated that one in every four Americans has used cocaine for its euphorigenic properties. With increasing participation of younger age subjects in the cocaine abuse, the effects of cocaine on the reproductive system have attracted considerable attention. The impact of cocaine abuse on the health and society has been repeatedly documented in the past, but its effects on human reproduction have only recently been appreciated. The initial reports, on the harmful effects of cocaine on pregnancy and neonatal outcome, documented high incidence of abortions, placental abruption and neonatal neurobehavioral abnormalities. Subsequent studies have confirmed these findings and have documented a high incidence of congenital malformations, intrauterine growth retardation, sudden infant death syndrome and premature labor and delivery following cocaine use. Additionally, since cocaine is freely excreted in the milk, its effects on nursing have raised serious concerns. In this review, the effects of cocaine on various elements of reproduction, namely endocrines, fertility, libido, intercourse, pregnancy, fetal development, childbirth, neonates and infants have been analyzed systematically. It is believed that a clearer understanding of the cocaine's effects on various aspects of reproduction is essential to counsel and treat the pregnant women and to protect the newborn. PMID- 8199752 TI - Effects of nocloprost clathrate on absorption of acetylsalicylic acid. AB - The cytoprotective prostaglandin E2 analog nocloprost clathrate (NOCLO) is tested as a prophylactic for gastrointestinal lesions of NSAID. The effects of 400 micrograms NOCLO versus respective placebos with and without equivalent amounts of beta-cyclodextrin on the pharmacokinetic behavior of acetylsalicylic acid (ASA), given 30 min after NOCLO, were studied in two single-blind, parallel-group trials. The trials were performed in 15 male healthy volunteers (age 21-25 years, body weight 62-94 kg, body height 172-187 cm) with known N-acetylation and debrisoquine type hydroxylation phenotype. ASA, salicylic acid (SA), and salicyluric acid (SU) in plasma and SA and SU in urine were measured by HPLC. NOCLO delayed the absorption of ASA (increased tmax, lower Cmax) significantly in comparison with both placebos. AUC and clearance values were not changed by NOCLO premedication. There were neither differences between the two placebo groups nor between the two groups pretreated with NOCLO with regard to any pharmacokinetic parameter. The changes in drug absorption are caused by the sum of those cytoprotective effects of prostaglandin which are also determinants of drug absorption. PMID- 8199754 TI - The management of epiglottitis in a small paediatric intensive care unit. AB - The aim of this study was to examine the outcome of epiglottitis in a small paediatric institution. Over the 5 year period October 1986 to September 1991, 44 children (of whom 15 were retrieved) with epiglottitis were admitted to the only paediatric intensive care facility in the Hunter Region. The so-called classical features were often absent. Forty of the 44 children were intubated. The mean length of intubation was 22 h and the mean length of hospital stay was only 2 1/2 days. One child had a respiratory arrest prior to intubation but made a complete recovery; one child had a coexistent submental/submandibular fascial space infection; 16 (36%) had abnormal chest radiographs. Five children had post extubation stridor with one of these children left with residual hoarseness. Epiglottitis can be managed safely in a small paediatric intensive care unit with acceptable short-term and long-term complications. PMID- 8199755 TI - Non-acute casemix in the Illawarra. AB - There are problems associated with the use of acute care diagnosis-related groups for prospective payment for rehabilitation medicine services. As a preliminary effort to assist in the development of the National Non-Acute Inpatient Casemix Project, a modified costing study was done in the rehabilitation and geriatrics ward of the Illawarra Regional Hospital; its aim was to assess the validity of the functional independence measure (FIM) and the resource utilization group (RUG) system as predictors of staff time involvement in inpatient rehabilitation services. Data collected on 51 patients over 3 months showed that in a standard Australian rehabilitation unit the costs of staff involvement varied depending on the type of functional impairment and severity of carer burden. The FIM alone was not predictive of rehabilitation costs and the RUG 2 instrument was not comprehensively predictive of cost. The RUG 3 instrument developed in the USA did not allocated weightings appropriate to Australian costs. If, however, functional impairment groups were combined with one of these measures of carer burden, then costs did fall into categories reflective of staff time involvement. An Australian system which incorporates an instrument measuring functional capacity may be useful for resource allocation in rehabilitation care. PMID- 8199756 TI - Incorporating peer review into routine clinical work: a practical example. AB - We describe a simple quality assurance (QA) exercise that compared the practices of two physicians providing geriatric consultations at a University teaching hospital. Two hundred consecutive referrals were randomly allocated to either physician. Although the patients referred had similar characteristics, their problems were managed differently. This led to an evaluation of work practices and identification of problems to which solutions were found. As the study was incorporated into routine clinical work, its cost in terms of resources and manpower was minimal. Such simple practical QA exercises should be used more extensively to enhance the practice of medicine. PMID- 8199758 TI - The lateral radiograph of neck in laryngo-tracheo-bronchitis (croup). AB - The films of 61 children who had a lateral radiograph of neck performed in the management of acute laryngo-tracheo-bronchitis were reviewed by a paediatric radiologist. He was unaware of the clinical history and the outcome of the children's illnesses. The clinical records of the same children were reviewed independently and information sought about the clinical relevance of the film results. Sixty per cent of the films were felt to be in keeping with a diagnosis of acute laryngo-tracheo-bronchitis. As judged by the information in the medical records these results did not influence the management of the children other than in one instance where a child underwent laryngoscopy. This decision was strongly influenced by the original film report. No child developed acute airway obstruction while in the Radiology Department. The findings of this study support the concept that a request for a lateral X-ray of neck in croup is an inefficient use of diagnostic facilities. PMID- 8199757 TI - Readmissions of day-only patients in NSW acute hospitals. AB - Day-only admissions have increased substantially over the last decade. With the increase in numbers, it is necessary to consider the quality of care of the patients undergoing a day-only admission. The readmission rate can be used as one such guide to quality of care. For several large Sydney hospitals, the percentage of patients readmitted was consistent across all lengths of stay (approximately 9%). When considering those type of admissions that are more suited to day surgery units, the readmission rate was 4.4%. This is suggestive of conservative selection criteria for day surgery unit patients. PMID- 8199759 TI - The trials, tribulations and achievements of implementing quality management. AB - Quality initiatives in the 1960s included Mortality and Morbidity Studies. In the 1970s Retrospective Audit was developed. In the 1980s Quality Assurance was the favoured option and was strongly promoted by The Australian Council on Healthcare Standards. In the 1990s the trend established across business and industrial organizations has been towards Quality Management. Health care services today are taking up this challenge and embarking on a new Quality journey. The importance of Quality Leadership in preventing frustration, rework and demotivation for individual participants of the organization should not be underestimated in implementing this Quality process. PMID- 8199760 TI - Child and adolescent psychiatric services: case audit and patient satisfaction. AB - A system for the monitoring and review of a large number of cases seen for assessment and outpatient treatment by a multidisciplinary child and adolescent psychiatric service is described. The system permits monitoring of all cases to closure, and clinical review of treatment for those cases whose outcomes are judged unsatisfactory by the treating clinician. It also allows monitoring of those cases in which there was patient dissatisfaction with the service, as expressed in a patient satisfaction questionnaire. The system of review has gained the acceptance of the clinical team, who are involved in its continued improvement. PMID- 8199761 TI - A multicentre exercise: developing an indicator for the physiotherapy management of acute low back pain. AB - The collection of information from a number of treatment centres is necessary for the development of diagnosis-specific treatment norms. From these data, realistic outcomes of treatment can be determined and significant risk factors identified. By comparing individual therapists' data with the overall treatment norms, acceptable levels of variation can be established. A prospective pilot study on acute low back pain, which examined both patient characteristics and outcomes of physiotherapy intervention, was conducted among one-third of the private physiotherapy practices in Tasmania. There was no previously developed methodology on which to base the study. As a result, the distribution of treatment numbers was first examined in order to flag the mean number of treatments. The outcome of the patient groups which fell on either side of the mean flag (the normal and outlying patient groups) was then defined. A clinical indicator was developed from both treatment numbers and outcome. PMID- 8199762 TI - Management of medical complications associated with stroke. PMID- 8199763 TI - Mental deterioration related to lacunar infarctions. PMID- 8199764 TI - Special report: cardiovascular disease in women. Special writing group. PMID- 8199765 TI - Rationale for a community approach to hypertension control among inner city minority populations. PMID- 8199766 TI - Prevention of hypokalemia caused by diuretics. AB - Hypokalemia induced by the use of diuretics is common. Those at risk include the elderly, women, patients with edematous states, and patients in whom higher doses and/or the more potent agents are used. Prevention should include a low-salt diet rich in potassium, magnesium, and chloride (either through foods enriched with these elements or through potassium chloride supplements) and use of low doses of short-acting diuretics in the treatment of mild to moderate hypertension. The subgroup of hypertensive patients in whom hypokalemia develops despite these recommendations may benefit from a change to the potassium-sparing diuretic spironolactone or substitution of diuretics with alternative first-line drugs. PMID- 8199767 TI - Pulsus paradoxus. PMID- 8199768 TI - Indications for use of permanent cardiac pacemakers. PMID- 8199769 TI - Hypertension management in the elderly. PMID- 8199770 TI - Flecainide: its value and danger. AB - Flecainide is an important addition to the therapeutic armamentarium because it is a potent agent for the treatment of paroxysmal supraventricular tachycardia in patients without structural heart disease. Flecainide also may be useful in patients with debilitating nonsustained ventricular arrhythmias in the absence of structural heart disease. It is rarely useful in the management of life threatening sustained ventricular arrhythmias. PMID- 8199771 TI - Sinus node dysfunction and ischemic stroke. PMID- 8199772 TI - Preparing patients and families for health care procedures. PMID- 8199773 TI - Assessment and diagnosis of cerebrovascular dementia. PMID- 8199774 TI - Nucleotide sequence and genetic analysis of the region essential for functional expression of the gene for ferredoxin I, fdxN, in Rhodobacter capsulatus: sharing of one upstream activator sequence in opposite directions by two operons related to nitrogen fixation. AB - Nucleotide sequencing of the region upstream of two ferredoxin genes, fdxC and fdxN, of Rhodobacter capsulatus revealed the existence of one open reading frame (ORF), ORFU1, in the same orientation as these genes and two other ORFs, ORFU2 and ORFU3, in the opposite orientation. Two potential -24/-12 promoters were found in front of ORFU1 and ORFU2, respectively, and there was a putative upstream activator sequence (UAS) or NifA-binding site between them. The ORFs corresponded to no known nif genes. However, analysis of their putative products showed that the product of ORFU1 (M(r) 47,912) and that of ORFU3 (M(r) 19,090) had a flavodoxin-like domain and a 2[4Fe-4S] ferredoxin-like domain, respectively, and that the product of ORFU2 (M(r) 20,424) was a hydrophobic protein with six potential membrane-spanning portions. Results of interposon mutagenesis and complementation experiments indicated that ORFU2 but not ORFU1 is essential for nitrogen fixation and that additional gene(s) essential for nitrogen fixation must be present in the unsequenced region adjacent to ORFU3. Translational fusion analysis involving lacZYA and fdxN or ORFU3 provided evidence that the putative UAS is responsible for regulation of both ORFU1-fdxC fdxN and ORFU2-ORFU3 operons in opposite orientations, and that the control of the latter is stricter than that of the former. PMID- 8199775 TI - Identification of a nifDK-like gene (ORF467) involved in the biosynthesis of chlorophyll in the cyanobacterium Plectonema boryanum. AB - The frxC gene, which is found in chloroplast DNA (ctDNA) and in cyanobacteria, encodes a protein that is required for the light-independent reduction of protochlorophyllide (Pchlide) to chlorophyllide a (Chlide). A DNA fragment downstream of frxC in the filamentous cyanobacterium Plectonema boryanum was cloned and analyzed. Sequencing of the DNA fragment revealed an open reading frame (ORF) that encoded a protein of 467 amino acid residues (designated ORF467), which showed extensive homology to the proteins encoded by genes on ctDNAs (ORF465 in liverwort, gidA in pine and chlN in Chlamydomonas reinhardtii) and to ORF469 protein of the cyanobacterium Synechocystis sp. strain PCC 6803. We isolated a targeted mutant YFM6D-3 in which ORF467 was inactivated by the insertion of a kanamycin-resistance gene into the coding region. YFM6D-3 exhibited a phenotype similar to that of YFC1004, an frxC-disrupted mutant, which did not synthesize chlorophyll (Chl) and accumulated Pchlide, a precursor to Chl, in the dark. These phenotypic characteristics of YFM6D-3 indicate that the light independent reduction of Pchlide requires not only the FrxC protein but also the ORF467 protein. The amino acid sequences of the homologues of ORF467 exhibit low but significant similarity to those of the alpha and beta subunits of nitrogenase MoFe-protein, suggesting a phylogenetic relationship between the light independent Pchlide reductase and nitrogenase, as is observed between the FrxC protein and the Fe-protein of nitrogenase. PMID- 8199776 TI - The presequence of a precursor to the delta-subunit of sweet potato mitochondrial F1ATPase is not sufficient for the transport of beta-glucuronidase (GUS) into mitochondria of tobacco, rice and yeast cells. AB - A precursor to the delta-subunit of sweet potato mitochondrial F1ATPase (pre-F1 delta) has an amino-terminal (N-terminal) presequence of 45 amino acid residues and its N-terminal 18 residues may form an amphiphilic alpha-helix, which is typical of mitochondrial targeting signals [Kimura et al. (1990) J. Biol. Chem. 265: 6079]. Fusion genes consisting of sequences that encoded the 25 (DG25), 46 (DG46) and 73 (DG73) N-terminal amino acids from pre-F1 delta fused to the N terminus of the coding sequence of bacterial beta-glucuronidase (GUS) were placed downstream of the 35S promoter of cauliflower mosaic virus and used to transform suspension-cultured tobacco cells, rice calli and tobacco plants. Fusion genes were also placed downstream of the yeast GAL10 promoter and introduced into Saccharomyces cerevisiae cells. In these transformed cells, only the DG73 GUS fusion protein was transported into mitochondria and subjected to proteolytic cleavage of the presequence. Neither transport to mitochondria nor processing of the presequence of the DG46 GUS-fusion protein, which contained the entire presequence and the processing site, occurred in either plant or yeast cells. These results indicate that the presequence of pre-F1 delta is not sufficient for the transport of the GUS protein into mitochondria in tobacco, rice and yeast cells. The requirement for the longer polypeptide from pre-F1 delta in the transport of the GUS protein into mitochondria could be due either to the lack of sufficient information for mitochondrial targeting within the presequence or to the nature of the passenger protein, GUS, used in this study. PMID- 8199777 TI - Identification of cytoplasmic and nuclear low-molecular-weight heat-shock proteins in tomato fruit. PMID- 8199778 TI - Amino acid sequence similarities between the vacuolar proton-pumping inorganic pyrophosphatase and the c-subunit of F0F1-ATPases. AB - Comparison of the Arabidopsis thaliana vacuolar proton-pumping inorganic pyrophosphatase with three F0F1-ATPase c-subunits revealed a strong similarity between a stretch containing amino acids 227-245 of the H(+)-PPase and a transmembrane alpha-helix of the c-subunits which contains the glutamate which binds N,N'-dicyclohexylcarbodiimide. PMID- 8199779 TI - Improving the management and knowledge of depression. PMID- 8199780 TI - Biological and hormonal aspects of postpartum depressed mood. PMID- 8199781 TI - Defeating depression in the developing world: a Zimbabwean model. PMID- 8199782 TI - Outcome of depression in psychiatric settings. AB - We reviewed follow-up studies of adults with depressive disorders seen in psychiatric settings, and noted outcomes in terms of recovery, recurrence, and persistent depression, at six months, one year, two to five years, and ten or more years after an index episode of depression. Recovery increased with time: about half recovered at least briefly by six months, and a large majority did so in the long term. Only about a quarter recovered from an index episode and remained well more than ten years thereafter. A quarter of patients suffered recurrence of depression within a year of an index episode, and three-quarters did so at least once during follow-up periods lasting more than ten years. For more than one in ten patients, the depression proved persistent, the proportion affected remaining relatively stable over time. The review highlighted a relative paucity of conclusive investigations on the outcome of the commonest psychiatric disorder in clinical settings. PMID- 8199783 TI - The peer review of "Outcome of depression in psychiatric settings". PMID- 8199784 TI - The social competition hypothesis of depression. AB - Depressive personality and depressive illness are examined from an evolutionary adaptationist standpoint. It is postulated that the depressive state evolved in relation to social competition, as an unconscious, involuntary losing strategy, enabling the individual to accept defeat in ritual agonistic encounters and to accommodate to what would otherwise be unacceptably low social rank. PMID- 8199785 TI - Defining melancholia: properties of a refined sign-based measure. AB - We hypothesised that psychomotor disturbance is specific to the melancholic subtype of depression and capable of defining melancholia more precisely than symptom-based criteria sets. We studied 413 depressed patients, and examined the utility of a refined, operationally driven set of clinician-rated signs, principally against a set of historically accepted symptoms of endogeneity. We specified items defining psychomotor disturbance generally as well as those weighted either to agitation or to retardation. We demonstrated the system's capacity to differentiate 'melancholic' and 'non-melancholic' depression (and the comparable success of DSM-III-R and Newcastle criteria systems) by reference to several patient, illness and treatment response variables, to an independent measure of psychomotor disturbance (reaction time) and to a biological marker (the dexamethasone suppression test). PMID- 8199786 TI - Future imperfect: the long-term outcome of depression. AB - During 1976, 80 patients with a primary depressive illness were selected from a consecutive series of referrals to the Royal Edinburgh Hospital for a short-term follow-up study. This paper concerns the 12-year longitudinal assessment of the survivors. During the follow-up, mortality risk for the sample was almost doubled. Of the series, 35% had experienced a recurrence within 2 years of the initial interview, and just over 60% within the entire study time of 12 years. The risk of recurrence was enhanced for those aged over 45 years at index, for those with a history of depressive disorder and for those who had not engaged in parasuicidal behaviour during the index episode. The observed effect of previous episodes was largely accounted for by age. The chance of recurrence was not affected by whether the treatment of the index episode included ECT, or by whether diagnosis was 'endogenous' or 'neurotic'. Application of the Lee-Murray outcome criteria showed that about one-third of the Edinburgh series experienced a very poor outcome. Results are presented concerning the prediction of long-term outcome as represented by the Depression Outcome Scale (DOS), a measure specially constructed for this study. PMID- 8199787 TI - Heterogeneity of depression. Classification of depressive subtypes by longitudinal course. AB - This paper describes the application of prospective longitudinal data from an epidemiological sample of young adults to define subtypes of major depression. Depression was classified on a spectrum from subthreshold manifestation of symptoms and duration at one end, to cases with recurrent episodes of depression meeting duration criteria for major depressive episodes at the other. There was a direct relationship between the severity of depression over the longitudinal course and both duration and recurrence of depressive episodes. The subgroup of depression with recurrence of both brief and longer duration episodes could be discriminated on most of the indicators of validity including symptoms, impairment, family history, and suicide attempts. In light of the young age of this cohort, the strong history of suicide attempts and other complications of depression among the subjects with recurrent depression was striking. These findings underscore the importance of employing course as a classification criterion of depression, and the inclusion of subthreshold episodes of depression in the characterization of course. PMID- 8199788 TI - Personality traits during depression and after clinical recovery. AB - We investigated whether and how acute depressive symptoms affect the self-report of maladaptive personality traits. Sixty-eight acutely depressed patients underwent the Structured Interview for DSM-III Personality Disorder (SIDP) before and after pharmacological treatment, allowing us to determine whether self reported maladaptive personality traits are different during depression and after successful clinical recovery. After the initial SIDP administration (during an episode of major depression), patients received desipramine treatment (dose range 150-300 mg/day) over a course of 4-5 weeks before readministration of the SIDP. For those who recovered from their depression (n = 39), cluster III trait scores were significantly lower than those assessed at baseline, and there was a lower frequency of cluster III categorical diagnoses for a personality disorder after treatment than before treatment. Recovered patients also had significantly lower cluster I personality trait scores after treatment as compared with baseline ratings. For those who did not recover from their depression after treatment (n = 29), cluster I trait scores were in fact higher than those measured at baseline, but there were no differences in categorical diagnoses before and after treatment. Cluster II personality traits and categorical diagnoses were not different between those who did and did not recover from their depression. Thus, depression may have a significant effect on the assessment of cluster I and cluster III personality traits. It is possible that cluster I and III 'personality traits' may be interwoven with depressive features and therefore subject to state influences, whereas cluster II personality traits may entail enduring, long-term characteristic modes of thinking, feeling, and behaving. PMID- 8199789 TI - Familial cosegregation of major affective disorder and Darier's disease (keratosis follicularis) AB - Darier's disease is a rare autosomal dominantly inherited keratosis. This is an account of one family in which there is co-occurrence of major affective disorder and Darier's disease in five members and absence of both disorders in five members. The pedigree is consistent with genetic linkage between the Darier gene and a major autosomal dominant susceptibility locus for major affective disorder. When the Darier's disease gene has been mapped, its chromosomal location will be an interesting candidate locus for linkage studies of major affective disorder. PMID- 8199790 TI - Bipolar affective puerperal psychosis associated with consanguinity. AB - Most clinical and genetic evidence suggests that puerperal psychosis is closely related to bipolar affective disorder. During a linkage study of bipolar disorder we ascertained a British family in which puerperal psychosis was associated with consanguinity in three sisters. All three subjects had lifetime RDC diagnoses of bipolar I or manic disorder. An inbred brother also had bipolar I disorder. The only female member of the sibship to escape puerperal psychosis was outbred. These findings are consistent with several genetic models for bipolar disorder in this family. The most interesting possibility is a single major susceptibility locus of recessive effect. Under this assumption, the family could be used for homozygosity mapping to help localise the putative recessive locus. If other inbred families can be found in which the same putative recessive locus is operating, the power to localise the gene by homozygosity mapping would be greatly increased. PMID- 8199791 TI - 5-HT1A receptor sensitivity in major depression. A neuroendocrine study with buspirone. AB - The hypothermic, growth hormone and corticotrophin (ACTH) responses to the 5-HT1A receptor agonist buspirone (30 mg orally) were measured in 20 unmedicated patients with major depression and 20 healthy controls. Compared with the controls, the hypothermic responses of the depressed patients to buspirone were significantly attenuated, particularly in patients with melancholic depression. In contrast, the responses of growth hormone and ACTH to buspirone were unchanged. The data suggest that major depression may be associated with impaired sensitivity of 5-HT1A autoreceptors but that the function of the post-synaptic 5 HT1A receptors that mediate growth hormone and ACTH release is unaltered. Within the limitations that attend the use of buspirone as a 5-HT1A probe, our data suggest that the decrement in serotonin neurotransmission at post-synaptic 5-HT1A receptors in depression is due to decreased serotonin release rather than impaired responsivity of post-synaptic 5-HT1A receptors. PMID- 8199792 TI - Depressive disorders in long-term survivors of stroke. Associations with demographic and social factors, functional status, and brain lesion volume. AB - Sixty surviving patients from a community-based stroke register who had computerised tomography (CT) scan evidence of a single brain lesion were interviewed three to five years after their first ever stroke. Depression (DSM III-R major depression, partially resolved major depression, and dysthymia) was present in 11 (18%) of the patients and was associated with impaired physical and cognitive functioning, greater age, residence in an institution, absence of a close personal relationship, and larger original brain lesion. Of these variables, only functional dependence (odds ratio 16.4; confidence interval 1.6 170), larger lesion volume (6.6; 1-50), and female sex (8; 1.1-56) remained significantly associated with depression after controlling for all other variables. We conclude that depression in long-term survivors of stroke has many of the same associations as depression in non-stroke elderly populations. Depression in long-term stroke survivors may also be associated with larger original brain lesions, although this requires confirmation in a prospective study. PMID- 8199793 TI - The nature of depression among older people in inner London, and the contact with primary care. AB - Ninety-six people of pensionable age from an inner-London electoral ward who had been identified by short-CARE screening as having 'probable pervasive depression' were interviewed further to ascertain their GMS-AGECAT and self-CARE status, comorbid features, and current primary-care psychiatric management. Estimated incidence rates of 30.8 per 1000 per year for 'probable pervasive depression' and 15.4 per 1000 per year for GMS diagnostic depression were calculated using results from a short-CARE screen in 1988. Among GMS diagnostic depression cases, anxiety was the major psychiatric comorbid feature (95%) and organic features were uncommon (8.4%). Of 66 self-CARE cases, 48 (73%) were also GMS-AGECAT cases; of 24 self-CARE non-cases, 15 (62.5%) were not GMS-AGECAT cases. Among subjects who had 'probable pervasive depression', 38% said that they had declared their symptoms to their general practitioner. Only 14% of subjects were prescribed antidepressants; 24% were prescribed hypnotics. Half the GMS-AGECAT-case subjects who stated that they had declared to their general practitioner were on specific therapy. Screening for depression and health education aimed at increasing psychological declaration are seen as ways forward in the management of this depression. PMID- 8199794 TI - Geomagnetic storms: association with incidence of depression as measured by hospital admission. AB - The hypothesis that geomagnetic storms may partly account for the seasonal variation in the incidence of depression, by acting as a precipitant of depressive illness in susceptible individuals, is supported by a statistically significant 36.2% increase in male hospital admissions with a diagnosis of depressed phase, manic-depressive illness in the second week following such storms compared with geomagnetically quiet control periods. There is a smaller but not statistically significant increase in female psychotic depression and non psychotic depression admissions following storms. There was no correlation between geomagnetic storm levels and number of male admissions with psychotic depression, which is consistent with a threshold event affecting predisposed individuals. Phase advance in pineal circadian rhythms of melatonin synthesis may be a possible mechanism of causation or be present as a consequence of 5 hydroxytryptamine and adrenergic system dysfunction associated with geomagnetic disturbance. Effects on cell membrane permeability, calcium channel activity and retinal magneto-receptors are suggested as possible underlying biochemical mechanisms. PMID- 8199795 TI - A. I. F. Scott & C. P. L. Freeman's "Edinburgh Primary Care Depression Study. AB - "OBJECTIVE--To compare the clinical efficacy, patient satisfaction, and cost of three specialist treatments for depressive illness with routine care by general practitioners in primary care. DESIGN--Prospective, randomised allocation to amitriptyline prescribed by a psychiatrist, cognitive behaviour therapy from a clinical psychologist, counselling and case work by a social worker, or routine care by a general practitioner. SUBJECTS AND SETTING--121 patients aged between 18 and 65 years suffering depressive illness (without psychotic features) meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition for major depressive episode in 14 primary care practices in southern Edinburgh. MAIN OUTCOME MEASURES--Standard observer rating of depression at outset and after four and 16 weeks. Numbers of patients recovered at four and 16 weeks. Total length and cost of therapist contact. Structured evaluation of treatment by patients at 16 weeks. RESULTS--Marked improvement in depressive symptoms occurred in all treatment groups over 16 weeks. Any clinical advantage of specialist treatments over routine general practitioner care were small, but specialist treatment involved at least four times as much therapist contact and cost at least twice as much as routine general practitioner care. Psychological treatments, especially social work counselling, were most positively evaluated by patients. CONCLUSIONS--The additional costs associated with specialist treatments of new episodes of mild to moderate depressive illness presenting in primary care were not commensurate with their clinical superiority over routine general practitioner care. A proper cost-benefit analysis requires information about the ability of specialist treatment to prevent future episodes of depression. PMID- 8199796 TI - Brain, mind, and behaviour. PMID- 8199797 TI - Brain, mind, and behaviour. PMID- 8199798 TI - Life events and relapse in bipolar disorder. PMID- 8199799 TI - Is there a lithium withdrawal syndrome? PMID- 8199800 TI - Morbidity among social phobics. PMID- 8199801 TI - Perinatal psychiatry: east is east and west is west. PMID- 8199802 TI - An attachment school of psychotherapy. PMID- 8199803 TI - Cannabis toxic psychosis while on disulfiram. PMID- 8199804 TI - Tricyclic-induced seizures and absent ECT response. PMID- 8199805 TI - Pain and seasonal affective disorder. PMID- 8199806 TI - [Alternative one lung ventilation anesthesia for bilateral thoracoscopic sympathectomy]. AB - Palmar hyperhidrosis (PH) is a common disorder in the oriental subtropical area. There have been many therapeutic methods, such as: oral medication, local treatment and traditional surgical operation, but none of them has proved entirely satisfactory. Since the development of video endoscopic surgery, transthoracic endoscopic sympathectomy has been increasing day by day. This study consisted of 124 PH patients under alternative one lung ventilation anesthesia for bilateral thoracoscopic laser sympathectomy. The age of patients ranged from 13 to 64 years, male 45 and female 79. The average anesthesia duration was 60 min. We used glycopyrrolate 0.03 mg/kg, decardon 1 mg/10 kg for premedication. Induction was with fentanyl 0.07 ml/kg, atracurium 0.6 mg/kg and thiopental 4 mg/kg. Maintenance was with isoflurane in 3L/min. oxygen inhalation. The alternative one lung ventilation anesthesia was achieved with double-lumen endobronchial tube. Fr 37, Fr 35, Fr 28 Sheridan Lt. double-lumen bronchial tube were used depending upon the sex and fudgement of the individual patient. All patients tolerated the procedure well so that sympathectomy could be performed smoothly and uneventfully. Immediately after the operation, a transient mild to moderate degree of difficult breathing and substernal discomfort were experienced in the majority of patients. These suffering often relieved spontaneously or with some common analgesic. PMID- 8199807 TI - [Experience of anesthesia during transthoracic endoscopic sympathectomy for palmar hyperhidrosis: comparison between double-lumen endobronchial tube ventilation and laryngeal mask ventilation]. AB - In the past year we had 36 patients operated for transthoracic endoscopic sympathectomy to treat palmar hyperhidrosis. The first group composed of 17 patients receiving anesthesia with double-lumen endobronchial-tube ventilation from July-92 to April-93, and the second group composed of 19 patients receiving anesthesia with laryngeal mask ventilation from April-93 to August-93. During right lung collapse for sympathectomy, the first group patients' SaO2 (oxygen saturation) decreased from 99.65 +/- 0.62 mmHg (pre-operation) to 95.12 +/- 5.48 mmHg (at cauterization), 95.24 +/- 5.41 mmHg (5 minutes after cauterization) and resumed 99.53 +/- 0.62 mmHg after the procedure completed. During left lung collapse for left side sympathectomy, the same group patients' SaO2 decreased from 99.59 +/- 0.62 mmHg to 97.35 +/- 3.06 mmHg, 97.82 +/- 2.53 mmHg and resumed 99.65 +/- 0.49 mmHg respectively. The second group using laryngeal mask ventilation had SaO2 changes during right side sympathectomy from 99.68 +/- 0.58 mmHg (pre-cauterization) to 99.74 +/- 0.45 mmHg (when cauterization), 99.79 +/- 0.42 mmHg (5 minutes after cauterization) and resumed 99.84 +/- 0.37 mmHg after the procedure completed. During left side sympathectomy the second group patients' SaO2 changed from 99.84 +/- 0.39 mmHg to 99.42 +/- 1.50 mmHg, 99.47 +/- 1.46 mmHg and resumed 99.74 +/- 0.59 mmHg respectively. After 2-Way ANOVA with repeated measures of the SaO2 value, we could see that no matter what side operation, there were differences existed between these two groups (< 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199808 TI - Thoracic epidural anesthesia for major abdominal surgery: a retrospective study. AB - In 1986-1988, the authors had experiences with thoracic epidural anesthesia for a variety of major abdominal operations in 303 patients. It is proved to be reliable and effective. The puncture levels were between T8 to T12. 2% lidocaine, in plain form or with 1:200,000 epinephrine, was used as anesthetic agent. Perioperative complications were carefully managed with satisfactory results. Post-operative conditions were evaluated and seemed to be superior to those of general anesthesia in many aspects. No patient had neurologic deficit as a result of the epidural anesthesia. We concluded that thoracic epidural anesthesia is an excellent alternative technique in major abdominal surgeries. PMID- 8199809 TI - Outcome of surgery and anesthesia in patients 80 years of age and older. AB - We studied retrospectively the outcome of surgery and anesthesia in 294 patients aged 80 and older who underwent 362 surgical procedures. Of these, 52 cases (14.4%) were admitted to intensive care unit (ICU) post-operatively. The 48-hour, 48-hour-to-30-day and overall mortality rates were 0.8%, 3.8% and 5.2% respectively. ICU. admission and mortality rate were closely associated with the ASA physical status classification. The overall mortality rates were 1.3%, 5.7% and 27% in class II, III and IV respectively. The respective ICU admission rates were 3%, 20% and 56%. ICU admission rate and mortality rate were 42.5% and 13.8% in emergency surgery vs. 5.8% and 2.5% in elective surgery. Patients with 3 or more co-existing diseases had the mortality rate of 23% and the rates of ICU admission and mortality for those with 3 or more peri-operative complications were 22% and 16% respectively vs. 11% and 4% for those with 2 or less peri operative complications. General surgery was associated with the highest mortality rate (15%) than other type of procedures. 22 of 74 cases who underwent intra-abdominal surgery required controlled ventilation for more than 24 hours post-operatively. 59% (13 cases) of such cases could not weaned successfully from ventilators and died subsequently. Only 2.5% (7 cases) of cases who underwent extra-pleural and extra-peritoneal procedures required controlled ventilation for more than 24 hours post-operatively. Of these, 2 died subsequently. For comparison, the study were artificially divided into two phases, each of three years long: they were the period from 1986-1988 and the period from 1989 1992.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199810 TI - Effects of magnesium sulfate pretreatment on succinylcholine-facilitated tracheal intubation. AB - Magnesium sulfate may prevent increase in serum potassium produced by succinylcholine and cause transient hypotension. The present study was designed to evaluate the effect of magnesium sulfate on heart rate, blood pressure and hyperkalemic response following succinylcholine injection during tracheal intubation. Twenty patients, ASA class I-II, scheduled for elective surgery were equally and randomly allocated to two groups. Heart rate, blood pressure, venous and arterial potassium levels were measured immediately before intubation. Induction was achieved with fentanyl 2 ug/kg and thiopental 5 mg/kg i.v., and intubation was facilitated with succinylcholine 1.0 mg/kg i.v. In the magnesium group (group I), 60 mg/kg of magnesium sulfate was infused intravenously in 1-1.5 min immediately before succinylcholine injection. The control group (group II) received an equal volume of normal saline in the same way. Heart rate, blood pressure, venous and arterial potassium levels were measured at 1, 3, 5 and 10 minutes after intubation. The results showed that magnesium sulfate could attenuate the hypertensive response at 1 minute and the hyperkalemic response at 1 and 3 minutes following succinylcholine-facilitated intubation; the tachycardiac response at 1 minute after intubation could not be reduced by this agent. We concluded that bolus infusion of magnesium sulfate may be of help in reducing the hypertensive response during laryngoscopy and intubation. PMID- 8199811 TI - Heart rate variability--a useful non-invasive tool in anesthesia. AB - Fluctuations in heart rate (HR) and arterial blood pressure occurring at respiratory and lower frequencies have long been recognized. However, their significance remained obscure until the monitoring of fetal heart-rate variability (HRV) was appreciated. Recent studies suggest that HRV may reflect the sympatho-vagal interactions that modulate cardiovascular function. Analysis of HRV can provide a noninvasive measure of central autonomic outflow and autonomic reflex functions. A mathematical and signal-processing technique called power spectral analysis (PSA) has been used extensively to quantify HRV. Several frequencies of HR oscillations can be quantified: the low-frequency peak (LFP 0 0.04 Hz), the mid-frequency peak (MFP 0.05-0.15 Hz) and the high-frequency peak (HFP 0.15-0.4 Hz). In this review article, the physiological origins of these HR fluctuations are described and the changes of HRV by different pathophysiological states are also discussed. In conclusion, spectral analysis of HRV may provide important insights regarding the influence of anesthesia on cardiovascular neural control and anesthetic depth and the monitoring may be developed as a very useful non-invasive tool for modern anesthesia in the near future. PMID- 8199812 TI - Experience of anesthesia for transthoracic endoscopic sympathectomy in palmar hyperhidrosis--110 cases. AB - Transthoracic endoscopic sympathectomy (TES) is an effective treatment for palmar hyperhidrosis. We review our experience and discuss the anesthetic technique and perioperative complications encountered in 110 patients undergoing TES for palmar hyperhidrosis. All patients were monitored with EKG, NIBP and pulse oximetry (SPO2) during the operation. The trachea was intubated with a single lumen endotracheal tube and ventilation was controlled manually. 100% inspired oxygen was necessary during TES to avoid hypoxia. One patient developed sudden cardiac arrest during electrocauterization of the left sympathetic chain and two patients required underwater drainage for hemothorax. Minimal pneumothorax was diagnosed in 4 patients and all cases resolved spontaneously without active treatment. PMID- 8199813 TI - [Pain control for liver transplants]. AB - Liver is the largest organ and is located in the right upper quadrant of the abdominal cavity. Surgery for liver transplantation is performed through a large skin incision, which gives considerable pain post operatively. We experienced 10 cases of liver transplant, 3 cases used meperidine 0.5 mg/kg intramuscularly, 3 cases used epidural morphine analgesia, and for the remainder 4 cases, we used morphine 2-3 mg intravenously as needed. Liver transplantation is a major surgery. It attracts media for reporting. The hospital administrator realized its importance to the hospital. A 24 hours special nursing team was provided. Addition analgesic medication was given intravenously in a bolus dose of 2-3 mg of morphine. All patients were able to communicate freely with the nursing team. The communication between the patient and nursing team is free. No post-analgesic hypotension or dyspnea were noted. Patients in all three groups were equally satisfied with their analgesic therapy post-operatively. As all patients expect pain after surgery, they were satisfied when the pain was less than what they had anticipated. Blood gases analysis was however better in patients with epidural morphine analgesia. PMID- 8199814 TI - Subcutaneous emphysema as a complication of laparoscopy--a report of two cases. PMID- 8199815 TI - [Anesthetic management of tetralogy of Fallot with absent pulmonary valve--a case report]. AB - Tetralogy of Fallot is characterized by a VSD, overriding of the aorta, right ventricular hypertrophy, and pulmonary stenosis. Absence of the pulmonary valve occurs in 2.6-6% of patients with tetralogy of Fallot. Operative procedures to relieve respiratory symptoms have been described with an mortality of 35-100%. Respiratory compromise may be severe in these infants secondary to bronchial compression by the aneurysmally dilated pulmonary arteries and present a different hemodynamic profile than those with classic tetralogy of Fallot. An understanding of the anatomic and physiologic principles and their anesthetic implications will lead to improved management of these extremely ill infants. We reported the anesthetic considerations and management of a case of tetralogy of Fallot with absent pulmonary valve of an infant who experienced severe respiratory distress on the supine position. PMID- 8199816 TI - [Comparison of double-lumen endobnonchial versus single-lumen endotracheal tube anesthesia in bilateral thoracoscopic sympathectomy]. AB - Since the development of video endoscopic surgery, the number of transthoracic endoscopic sympathectomy has been increasing. The use of double-lumen endobronchial tube or single-lumen endobronchial tube during anesthesia for these surgeries has been a controversial. 385 palmar hyperhidrosis patients divided into three groups: group I, under alterative one lung ventilation anesthesia with double-lumen endobronchial tube; group II, under alterative one lung ventilation anesthesia with single-lumen endobronchial tube; group III, under two lung ventilation anesthesia with single-lumen endobronchial tube were studied. All had received bilateral thoracoscopic sympathectomy. The age of patients ranged from 8 to 64 years old. There were 154 male and 231 female. The average anesthesia durations for group I, II and III were 38.56 +/- 10.28, 34.14 +/- 5.21, 31.83 +/- 3.34 min respectively. The variables considered in the study were: physique of the patients; duration of anesthesia; airway pressure changes; SaO2 changes during the operation and post-anesthesia complaints. We found that upon using double-lumen endobronchial tube, SaO2 levels was better maintained especially in the obese patients and the patients who had received a traditional surgical operation before. PMID- 8199817 TI - Vasectomy and vasectomy reversal. AB - Vasectomy remains the safest method of birth control and there is much to commend it in the setting of a stable family relationship. However, some aspects of this operation have been wrongly presented in an attempt to widen its popularity and increase public acceptance. A simple procedure it may be but it is not totally free of complications; sometimes the operation has to be repeated and rarely it may reverse spontaneously even after the most stringent precautions. The family planning officer who counsels a prospective candidate and the surgeon who undertakes the procedure must ensure that these facts are understood by the patient with crystal clarity and that this fact is duly recorded on a signed and witnessed permission slip. Any organization which includes vasectomy in its programme of family planning should include advice and referral for vasectomy reversal in exactly the same way that the pill may be stopped or a coil can be removed. Fertility can be successfully restored by vasovasostomy in 50% of men who wish to have their vasectomies reversed, which often is due to a change in circumstances beyond their direct control. PMID- 8199818 TI - Sir Henry Thompson BT, the first English urologist. AB - Sir Henry Thompson was a gifted Victorian. As a surgeon he achieved early recognition by successfully removing King Leopold of Belgium's bladder stone where two other eminent surgeons had failed. He was undoubtedly the most famous surgeon of his age, a position he was to occupy for some 30 years. As well as professional eminence he achieved success in an extraordinarily wide range of endeavours. He was an accomplished artist, exhibiting 12 times at the Royal Academy, a connoisseur and collector of china, a keen astronomer, an authority on diet and cooking and a pioneer advocate of cremation. He was interested in poultry-farming, market-gardening and photography. He published two novels sandwiched between a book on tumours of the bladder and another on the prevention of calculous disease, He was a celebrated host and his dinners--called 'Octaves'- at which he served eight courses to eight guests were legendary. To be invited meant one had 'arrived'. He was friendly with artists, scientists and men of letters--Huxley, Browning, Ray Lankester and Thackeray. At the age of 80 he bought himself a motor-car and 2 years later wrote a book on the anatomy of the motor-car engine. Sir Zachary Cope described him as a versatile Victorian, a fitting description of an extra-ordinarily gifted man. A commanding and slightly intimidating figure with little sense of humour, he achieved distinction in professional, artistic and social circles. Not only did he leave his mark on urology he left his mark on Victorian England. PMID- 8199819 TI - Radiographic evaluation of renal trauma: evaluation of 1103 consecutive patients. AB - OBJECTIVE: To review the records of patients with suspected urinary tract trauma to determine whether eliminating imaging studies would have missed any significant injuries. PATIENTS AND METHODS: The records of 1103 consecutive patients who underwent radiographic evaluation of the urinary tract because of suspected renal trauma were evaluated retrospectively. A comprehensive review was made of the group of patients who were normotensive and had only microscopic haematuria. RESULTS: Abnormal intravenous pyelograms (IVP) were found in 10% of patients with normotension and microscopic haematuria. In patients with injuries due to penetrating trauma, five of 16 with an abnormal IVP required operative intervention, while in patients with injuries due to blunt trauma, only one of 60 had a significant renal injury. None of the 605 patients with a blunt injury, microscopic haematuria, no history of hypotension, and no significant associated injuries required operative intervention solely for the renal injury. CONCLUSION: Radiographic evaluation of the urinary tract is recommended for all patients with penetrating trauma and any degree of haematuria, but only for patients with blunt trauma if associated with gross haematuria, microscopic haematuria and hypotension, or microscopic haematuria and significant associated injuries. PMID- 8199820 TI - Serum level of immunosuppressive acidic protein in haemodialysis patients with or without renal cell carcinoma. AB - OBJECTIVE: To assess the significance of immunosuppressive acidic protein (IAP) for detection of renal cell carcinoma in patients undergoing haemodialysis. PATIENTS AND METHODS: The serum concentration of both IAP and creatinine was measured in 74 patients undergoing haemodialysis, 10 of whom had renal cell carcinoma and 64 of whom had no renal cell carcinoma. Control data was obtained from 13 healthy blood donors. RESULTS: The serum IAP level of patients undergoing haemodialysis was significantly elevated compared with that of the controls. The serum level of IAP in patients with renal cell carcinoma who were undergoing haemodialysis was also considerably higher than that of patients with no renal cell carcinoma. The serum creatinine levels were not significantly different between patients with and without renal cell carcinoma but were significantly elevated when compared with the controls. CONCLUSION: The measurement of serum IAP concentration is of value in the detection of renal cell carcinoma in patients undergoing haemodialysis. PMID- 8199821 TI - Urinary calcium oxalate saturation in 'stone formers' and normal subjects: an application of the EQUIL2 program. AB - OBJECTIVE: To produce an index of lithogenic risk which identifies patients at risk of stone recurrence and facilitates the monitoring of prophylactic treatments. PATIENTS AND METHODS: The EQUIL2 program provides an evaluation of the state of urinary saturation, particularly of calcium oxalate, based on the pH and total concentrations (mmol/l) of sodium, potassium, calcium, magnesium, uric acid, chloride, ammonium, citrate, phosphate, sulphate, oxalate, pyrophosphate and carbon dioxide. The morning urinary calcium oxalate saturation coefficient was thus calculated for 30 stone-formers (Group 1) and 30 normal control subjects (Group 2). RESULTS: Urine from the majority of individuals was saturated, with no significant difference between the two groups. There appeared to be a correlation between the state of saturation and the urinary calcium oxalate molar product in both stone-formers (r = 0.931) and controls (r = 0.914). CONCLUSION: In future studies on urinary calcium oxalate saturation, it should be possible to supplement the sophisticated coefficient determined by the EQUIL2 program with the molar product, except in cases where monitoring therapies have little or no effect on urinary oxalate or urinary calcium levels. PMID- 8199822 TI - Alkali citrate prophylaxis in idiopathic recurrent calcium oxalate urolithiasis- a prospective randomized study. AB - OBJECTIVE: To assess the efficacy of alkali citrate therapy in patients suffering from recurrent idiopathic calcium oxalate stone formation. PATIENTS AND METHODS: Fifty patients suffering from active stone formation who had had at least one stone annually over the previous 3 years were recruited and randomly divided into two groups. They were given either general prophylactic instructions, i.e. abundant liquid intake and dietary restrictions (group I, n = 25)--or were additionally treated with alkali citrate (group II, n = 25). RESULTS: In group I, the rate of stone formation was reduced from 1.8 to 0.7 stones per patient per year. Similar results were obtained for group II, the corresponding figures being 2.1 and 0.9. There was a statistically significant higher urinary citrate excretion in group II than in group I. No difference was seen between the two groups regarding recurrent stone formation (Student's t-test). Stone formation decreased in both groups (group I 27%, group II 31%). Subjectively, 56% of group II patients, all of whom had previously experienced severe colic, reported spontaneous stone elimination to be painless, whereas in group I all but one patient suffered pain. CONCLUSION: An objective benefit of alkali citrate could not be established. PMID- 8199823 TI - Radiographer-performed abdominal and pelvic ultrasound: its value in a urology out-patient clinic. AB - OBJECTIVE: To assess the efficacy of radiographer-performed ultrasound examination as a routine investigative procedure in a urological out-patient clinic. PATIENTS AND METHODS: A total of 151 patients attending a District General Hospital Urological Out-patient Department underwent an ultrasound examination in the clinic. RESULTS: Diagnosis by ultrasound was achieved in 93% of patients. The remaining patients underwent further investigations. Two (1%) patients with normal scans had small bladder tumours. Subsequent intravenous urography in these individuals showed normal upper tracts. CONCLUSION: Abdominal and pelvic ultrasound examination performed in the urological out-patient clinic on unprepared patients was the only investigation necessary for evaluation of common problems such as non-specific urinary symptoms, recurrent urinary tract infections and bladder outlet obstruction. PMID- 8199824 TI - Histological response to injected Polytef and Bioplastique in a rat model. AB - OBJECTIVE: To study, using a rat model, the tissue reaction in response to the migration of particulate plastics injected into the lungs and subcutaneous sites. MATERIALS AND METHODS: A total of 50 rats were included in the study. Histological examination of 30 rats was carried out up to 6 months after the subcutaneous injection of 0.1 ml of either Polytef or Bioplastique. Specimens from a further 18 rats underwent histological examination up to 3 months after the intravenous injection of 0.01 ml of either Polytef or Bioplastique. Two rats were injected with normal saline to act as controls. Representative sections of multiple organs were taken from each animal. RESULTS: No systemic migration from the site of initial implantation was detected. This may have been due either to the animal used or to the limited number of sections taken. However, the intravenously injected plastics were found adjacent to the pulmonary arterioles 3 months after injection. The histological reaction at the local injection and lung sites was similar, with the giant cells being larger and the degree of fibrosis greater for Bioplastique than for Polytef. CONCLUSION: The histological reaction to Polytef and Bioplastique was similar in both the subcutaneous and lung sites. No migration or malignant change was seen. PMID- 8199825 TI - Trends in death rates and registration rates for prostate cancer in England and Wales. AB - OBJECTIVE: To describe trends in deaths from prostate cancer between 1970 and 1990, and trends in registrations of prostate cancer between 1971 and 1986. METHODS: Data on prostate cancer deaths and registrations were obtained from the Office of Population Censuses and Surveys, and age specific rates were calculated. RESULTS: The number of deaths from prostate cancer rose by 107% between 1970 and 1990, from 3906 to 8098. The number of registrations of prostate cancer rose by 75% between 1971 and 1986, from 5819 to 10,180. Age-specific death rates and registration rates also increased but by a smaller amount than the rise in absolute numbers. CONCLUSIONS: A component of the increase seen in both the number of prostate cancer deaths and registrations can be explained by a concomitant increase in the elderly male population, the group at highest risk, but the rises seen in rates are more difficult to explain. The rises are likely to have had considerable implications for the workload of urologists and should be taken into account when planning future health services. With further increases expected over the next decade in the elderly male population, deaths and registrations from prostate cancer will continue to rise. Research will be required to determine possible reasons for the increase seen in prostate cancer rates over the last 20 years, to determine the true incidence and prevalence of prostate cancer in the general population and to identify possible aetiological factors. PMID- 8199826 TI - Smoking and drinking habits in relation to prostate cancer. AB - OBJECTIVE: To evaluate the role of tobacco and alcohol consumption in the aetiology of prostate cancer. PATIENTS AND METHODS: In a case-control study conducted in the Netherlands, information on smoking and drinking habits was obtained from questionnaires completed by 345 patients exhibiting primary prostate cancer and by 1346 controls with benign prostate hyperplasia. The response rate was 79%. RESULTS: No association was observed between drinking habits and the risk of prostate cancer (324 cases versus 1237 controls; odds ratio 1.36; 95%CI 0.84-2.22). A significantly elevated odds ratio was found for individuals who had smoked at any time during their lives (329 cases versus 1212 controls; odds ratio 2.12; 95%CI 1.24-3.62). However, no relationship was observed between the number of cigarettes smoked, the duration of smoking, the age at which the subjects started smoking or with the calendar period in which they were born. Odds ratios calculated for individuals who smoked in consecutive 5-year periods between 1940 and 1989 did not show any trend. Furthermore, the risk of prostate cancer among ex-smokers did not differ significantly from the risk among current smokers, even when smoking was stopped more than 25 years previously. CONCLUSION: From these findings, which do not point to the causative agent, it would appear that neither smoking nor alcohol consumption seriously increases the risk of prostate cancer. PMID- 8199829 TI - Ectopic human chorionic gonadotrophin (HCG) production: is the detection by serum analysis of HCG of clinical relevance in transitional cell carcinoma of the bladder? AB - OBJECTIVE: To assess the potential value of ectopic beta-human chorionic gonadotrophin (beta HCG) measurement in the clinical management of transitional cell carcinoma (TCC). PATIENTS AND METHODS: A prospective serological study of 163 consecutive patients undergoing cystoscopy as new or review cases was performed to assess any correlation between beta HCG production and histological grading or stage. RESULTS: Ten per cent of patients with TCC had a raised beta HCG level but there was no correlation with tumour differentiation, staging or prognosis. CONCLUSIONS: beta HCG has no role as a tumour marker for TCC and therefore appears unlikely to play a part in the clinical management or treatment of urothelial tumours. PMID- 8199827 TI - Efficacy of the combination of nilutamide plus orchidectomy in patients with metastatic prostatic cancer. A meta-analysis of seven randomized double-blind trials (1056 patients). AB - OBJECTIVE: To review the efficacy of the combination of the anti-androgen nilutamide (Anandron) plus orchidectomy in patients with stage D prostate cancer who had received no previous treatment. PATIENTS AND METHODS: The results of seven randomized double-blind trials were analysed. In these studies patients were followed up until progression of disease or withdrawal for other reasons. Bone pain, urinary symptoms, performance status, levels of prostatic acid phosphatase (PAP) and alkaline phosphatase (AP) were evaluated before treatment and after 1, 3, 6, 12 and 18 months of treatment. Bone scans and X-rays were taken every 6 months. The best objective response, the time of progression and the time of death were recorded. The changes from baseline in symptoms and levels of tumour markers at month six and the percentages of objective regressions in the two treatment groups were compared using the Cochran-Mantel-Haenszel test stratified by study. Peto's method was used for the analysis of time to progression and of survival. RESULTS: Of the 1191 patients enrolled in all the original trials, 1056 were eligible. In the group of patients treated with nilutamide 50% had complete or partial regression of disease compared with 33% of those who were given a placebo (P < 0.001); bone pain and levels of PAP and AP were improved or returned to normal significantly more frequently (P < 0.01); the odds of disease progression were significantly reduced (odds ratio 0.84, P = 0.05); the odds of death from cancer and from other causes were reduced but the difference was not statistically significant. CONCLUSIONS: The combination of nilutamide and orchidectomy has a beneficial effect on pain of metastatic origin, levels of tumour markers, the objective response of disease and the time to disease progression. This treatment combination might also improve survival. PMID- 8199828 TI - Prognostic factors in pTa-pT1 superficial bladder tumours treated with intravesical instillations. The Dutch South-Eastern Urological Collaborative Group. AB - OBJECTIVE: To identify prognostic factors that enable patients with superficial bladder cancer to be divided into groups who will probably respond to therapy and those who will not. PATIENTS AND METHODS: In a prospective randomized study 387 patients with pTa-pT1 superficial bladder carcinoma received, after transurethral resection, intravesical instillations with immuno- or chemotherapy. A simultaneous computerized analysis of factors predicting the recurrence-free interval was performed. All these patients had negative random biopsies. Pretreatment factors analysed for recurrence were gender, age, history (primary or recurrent disease), location of tumour, number of tumours, pT-stage and grade. RESULTS MEDIAN: Follow-up was 27 months (range 12-56). During the follow-up period 37.2% of the patients had recurrence and eight patients (2.2%) had progression into muscle invasive disease. After a univariate analysis the number of tumours and location of the tumour in the bladder appeared to be a significant influence on the recurrence-free interval. Location of at least one of the tumours in the prostatic urethra, bladder neck, posterior wall, and trigone area was significantly related to a shorter recurrence-free interval; these areas were defined as high risk. Tumour stage showed borderline significance. By using multivariate methods to assess the relative importance of these factors, location of tumour in the high risk region was related especially to a short recurrence free interval. The factor found to be of significance for the prognosis for recurrence was tumour multiplicity. Gender, age, history of recurrent disease, size of the largest tumour, tumour stage or grade gave no additional information about the risk of recurrence. CONCLUSION: Prognostic factor analysis, as an auxiliary study of trials of patients treated for superficial bladder tumours, is mandatory. The prognostic factors related to recurrence-free interval found in this study, location of the tumour and multiplicity, may be of use in the stratification necessary for current protocol design. PMID- 8199830 TI - Pelvic floor activity patterns: comparison of nulliparous continent and parous urinary stress incontinent women. A kinesiological EMG study. AB - OBJECTIVE: To introduce neurophysiological methods to search for damage to neuromuscular structures involved in sustaining continence in women who experienced stress urinary incontinence during pregnancy and/or after delivery. PATIENTS AND METHODS: Eight stress urinary incontinent parous women (mean of 2.75 vaginal deliveries [range 2-4] median age 45.3 years [range 31-60]) were examined using simultaneous electromyogram recordings of the left and right pubococcygeus muscle via wire electrodes. Comparisons were made with 10 nulliparous continent women (median age 27.2 years [range 22-32]). RESULTS: Individual muscle activation patterns in stress urinary incontinent parous women were in principle similar to those observed in the continent nulliparous women, with two significant exceptions: (i) voluntary 'squeeze' showed significant differences in the holding time between the parous stress urinary incontinent patients and the nulliparous continent controls, with an empty bladder (49.0 s versus 193.9 s median value) and a full bladder (39.2 s versus 198.4 s); (ii) asymmetrical and uncoordinated levator activation patterns were demonstrated in four of eight parous stress incontinent women, i.e. inhibition of motor unit firing on coughing (n = 3) and dissociated recruitment of motor units during voluntary and reflex activation (n = 1). CONCLUSION: Childbirth appeared to induce both quantitative and qualitative changes in the pelvic floor which jeopardized the continence mechanism. Sphincter weakness appeared to result not only from the loss of motor units but also from altered activation patterns in the remaining units: shorter activation periods, lack of response or paradoxical inhibition. Kinesiological EMG recordings revealed behavioural abnormalities which appeared relevant for planning treatment. PMID- 8199831 TI - Correction of recurrent stress urinary incontinence by needle urethropexy with a vaginal wall sling. AB - OBJECTIVE: To review the results of a modification of the transvaginal needle urethropexy as a treatment for patients developing recurrence after surgical correction of stress urinary incontinence (SUI). SUBJECTS AND METHODS: Twelve women who had undergone previous surgery for SUI and had developed recurrence of the symptoms were treated by a needle urethropexy technique which employed an island of in situ vaginal skin as a sling to support the bladder neck and urethra. RESULTS: After a mean follow-up of 17.3 months, eight of the patients obtained excellent results, three experienced improvement and one was a failure. CONCLUSIONS: The vaginal wall sling needle urethropexy was a simple technique to perform and carries a low morbidity. The results are similar to those of the more elaborate traditional sling procedures reported in the literature. PMID- 8199832 TI - Reducing the loss of implants following penile prosthetic surgery. AB - OBJECTIVE: To assess the factors associated with loss of implant following penile prosthetic surgery and to make alterations in the management of patients to prevent this from occurring. PATIENTS AND METHODS: A retrospective analysis was carried out of the factors associated with post-operative infection and erosion in 188 patients who underwent implantation of penile prostheses. A prospective study was then established in which 62 patients were managed by a set protocol designed to counteract the factors identified as being contributory to loss of implants in the retrospective review. RESULTS: In the retrospective study nine (4.8%) patients lost a prosthesis due to erosion. Erosion was noted to be more common with one type of implant which has since been modified. Infection was the cause of prosthesis loss in 12.2% of patients in the retrospective review. The new protocol resulted in a significantly reduced infection rate in penile prostheses to 1.6% (P < 0.05). CONCLUSION: With attention to simple antiseptic prophylaxis, antibiotic penetration and continuing audit, a significant improvement in the loss of penile prostheses can be achieved along with a reduction in the amount of antibiotics prescribed. PMID- 8199833 TI - Use of a eutectic mixture of local anaesthetics in the release of preputial adhesions: is it a worthwhile alternative? AB - OBJECTIVE: To see if a eutectic mixture of local anaesthetics (EMLA) could be used effectively for the release of preputial adhesions as a day case procedure. PATIENTS AND METHODS: A total of 36 consecutive symptomatic children had their preputial adhesions separated under local anaesthetic with EMLA. RESULTS: The procedure was successful in 27 children. Of these, 16 remained symptom free at 9 to 12 months follow up although five children had slight recurrence of adhesions. The other 11 children were listed for circumcision at 2 weeks following the procedure because of marked recurrence of adhesions. CONCLUSION: EMLA cream is a good alternative to general anaesthetics in the separation of preputial adhesions. The technique is operator-dependent and better results were obtained when one person was using it regularly. Separation of adhesions is a worthwhile procedure in boys with symptomatic non-retractile foreskins. PMID- 8199834 TI - Epidermoid cyst of the testis: a review of clinical and histogenetic considerations. AB - OBJECTIVE: To review the records of patients with epidermoid cysts and those with germ cell tumours to determine the most appropriate method of treatment. PATIENTS AND METHODS: The records of the patients treated for epidermoid cysts and testicular germ-cell tumours in a period covering 22 years were analysed retrospectively. Nine specimens with an epidermoid cyst were examined by immunohistology for the presence of testicular intraepithelial neoplasia (TIN) (or carcinoma in situ of the testis). RESULTS: Ten patients with a simple epidermoid cyst and 481 patients with testicular germ-cell tumour were treated during the observation period. The relative incidence of epidermoid cysts in relation to the number of patients with testicular germ-cell tumours was 2.1% (95% confidence interval 0.8-3.35%). The mean age of the 10 patients with an epidermoid cyst was 24.1 years. The right testis was affected in seven patients and the left in three. Six of these patients received conservative surgery with excellent cosmetic results. No relapse had occurred after a median observation period of 30 months. Immunohistological staining for placental alkaline phosphatase disclosed the absence of TIN in the parenchyma surrounding the cysts. CONCLUSION: The absence of TIN calls into question the common assumption that an epidermoid cyst constitutes a monodermal teratoma. Two distinct entities of epidermoid cyst are proposed--one occurring in conjunction with a teratoma or a germ cell tumour (a 'complex' or 'mixed' epidermoid cyst) and the other a 'simple' epidermoid cyst without TIN in the adjacent tissue and thus representing a benign neoplasm that is not a teratoma. The absence of TIN near a simple epidermoid cyst justifies testis-sparing surgery. PMID- 8199835 TI - Ejaculation in men: a dynamic endorectal ultrasonographical study. AB - OBJECTIVE: To study the ejaculatory mechanisms in men using a dynamic endorectal ultrasonographical approach. SUBJECTS AND METHODS: Seven recordings were made of a young healthy volunteer during ejaculation, scanning the longitudinal plane from the bladder neck to the bulbous urethra. RESULTS: The study demonstrated the existence of a pre-ejaculatory phase characterized by a notable decrease in echogenicity of the inner prostate gland, due to the contraction of the pre prostatic sphincter 13-25 s before ejaculation. Several stages were recorded including an ejaculatory stage with an initial prostatic emission phase lasting 2 20 s and a posterior emission phase through the ejaculatory ducts lasting 3-14 s, with a seminal stoppage of 3-8 s, and finally a urethro-vesical reflux of a minimal fraction of the ejaculate over 5-9 s. The bladder neck and inner gland returned to their resting configuration between 10 and 90 s after ejaculation. CONCLUSIONS: Endorectal ultrasonographical imaging during ejaculation, a recently developed diagnostic procedure, may provide a new approach to ejaculation-related problems. PMID- 8199836 TI - Vasectomy reversal--microsurgery for best results. AB - OBJECTIVE: To determine whether microsurgery achieves a better result in vasectomy reversal than other macroscopic techniques. PATIENTS AND METHODS: A series of 103 consecutive patients with a median age of 36 years (range 26-58) who underwent microsurgical vasovasostomy was studied. The method employed was a modification of a two-layer anastomotic technique. In the first 49 patients 8/0 Vicryl was used to create a two-layer anastomosis whereas in 54 patients 10/0 Ethilon was used. RESULTS: Sperm were present in the ejaculate in 85% of patients who underwent bilateral vasovasostomy. The rate increased to 94% in those in whom 10/0 Ethilon had been used as the suture material but the difference was not statistically significant. In half of the patients sperm concentration, quality and motility improved over the 12 months following reversal. The fertility rate, measured between 8 months and 5 years after vasovasostomy, was 64% if the vasectomy had been performed within 10 years and fell to 39% if 10 years or more had elapsed. In the 10 patients who had undergone a failed reversal attempt elsewhere four had sperm in the ejaculate and two of these patients became fertile. CONCLUSION: The additional time and effort required for a microsurgical approach to vasovasostomy were worthwhile to obtain patency and fertility rates which were superior to those of other techniques. PMID- 8199837 TI - Transrectal Tru-cut biopsy of the prostate using a protective sheath. PMID- 8199838 TI - Endoscopic localization prior to partial cystectomy. PMID- 8199839 TI - Leydig cell tumour of the testis associated with Klinefelter's syndrome and Osgood-Schlatter disease. PMID- 8199840 TI - An uncommon complication of circumcision. PMID- 8199841 TI - Spontaneous perforation of an ileal neobladder. PMID- 8199842 TI - Dracunculiasis causing urethral fistula. PMID- 8199843 TI - Post-traumatic adrenal haematoma with massive adrenal enlargement and compression of the vena cava. PMID- 8199844 TI - Pyelo-duodenal fistula: a new method of closure. PMID- 8199845 TI - Acute renal failure due to bladder diverticula. PMID- 8199846 TI - Seminal vesicle cyst, renal agenesis and infertility in a 32-year-old man. PMID- 8199847 TI - Extracorporeal shock wave lithotripsy in an 8-month-old infant. PMID- 8199848 TI - Magnetic resonance imaging in the identification of an otherwise undetectable upper pole moiety. PMID- 8199849 TI - Magnetic resonance imaging in the identification of an otherwise undetectable upper pole moiety. PMID- 8199850 TI - Stimulation of the hypothalamus initiates the urethrogenital reflex in male rats. AB - The urethrogenital (UG) reflex is a spinal sexual reflex which is tonically inhibited in the intact male rat by neurons in the nucleus paragigantocellularis (nPGi). The medial preoptic area of the hypothalamus (MPOA) is involved in the activation of male sexual behavior. The present study examines the effect of hypothalamic stimulation on the UG reflex in the intact male rat. Areas of the hypothalamus were stimulated bilaterally with either electrical stimulation or D,L-homocysteic acid (DLH) and the presence of the UG reflex examined. Stimulation of discrete aras of the hypothalamus evoked the UG reflex. The UG reflex could be initiated in the absence of genital stimulation. Microinjections of DLH into the MPOA also initiate the UG reflex. These data suggest that stimulation of neurons in the MPOA overcome the inhibition by the nPGi and facilitate spinal genital reflexes leading to ejaculation. PMID- 8199851 TI - Intracellular calcium responses of circadian pacemaker neurons measured with fura 2. AB - The circadian pacemaker in the eye of the mollusk Bulla gouldiana is located within basal retinal neurons (BRNs) that express a circadian rhythm in cell culture. Light and other depolarizing stimuli shift the phase of the pacemaker in the eye through a process that requires extracellular calcium and is blocked by Ni2+. To test directly if an influx of Ca2+ is present throughout depolarizing treatments that produce phase shifts, dissociated BRNs in cell culture were loaded with a membrane-permeable form of the calcium-sensitive dye fura-2, and then depolarized with elevated levels of extracellular K+. Calcium levels in the BRNs remained elevated during treatments with 50 mM K+ lasting 1 h, a sufficient duration to phase shift the circadian pacemaker. Lowering extracellular free Ca2+ (approx. 1.7 x 10(-7) M) during depolarization blocked the rise in intracellular Ca2+, verifying that a Ca2+ influx is required. The sustained Ca2+ elevation during depolarization was also prevented with 50 mM Ni2+, which blocks phase shifts of the rhythm to depolarization, but not with 5 mM Ni2+, which does not block phase shifts. The initial rise in [Ca2+]i in response to 50 mM K+ was largest on average during the subjective night. The results show that a critical portion of the entrainment pathway persists in pacemaker neurons during cell culture, and that the phase-shifting stimulus may depend on a prolonged Ca2+ signal. PMID- 8199852 TI - Colocalization of octopamine and FMRFamide related peptide in identified heart projecting (DUM) neurones in the locust revealed by immunocytochemistry. AB - Immunocytochemical techniques are employed to reveal colocalization of octopamine with FMRFamide related peptide in the locust ventral nervous system. In each unfused pregenital abdominal ganglia (A4-A6) there are 3 octopamine-like immunoreactive neurones. By combining intracellular Lucifer yellow staining with subsequent immunocytochemistry these are individually identified as the efferent dorsal unpaired median (DUM) neurones DUM-1 and DUM-2, which innervate abdominal tergal and respectively sternal skeletal muscles, and DUM heart-1, an FMRFamide like immunoreactive neurone which projects to the heart and associated alary muscles. Colocalization of octopamine- and FMRFamide-like immunoreactivity in DUM heart-1 is verified by alternate staining of consecutive sections. With respect to locust ventral ganglia, this investigation shows that colocalization of octopamine with an FMRFamide related peptide is restricted to a single DUM cell occurring in each abdominal ganglion 2-7, which most likely corresponds to segmental homologues of DUM heart-1. PMID- 8199853 TI - Dendritic orientation of thalamocortical projection neurons in the ventrobasal complex of macaques. AB - This study describes the orientation of dendritic arbors from intracellularly labeled thalamocortical projection (TCP) neurons of Macaca fascicularis or Macaca mulatta. All neurons were located in the ventrobasal complex and responded to non noxious stimuli. Each neuron was composed of dendrites that varied considerably in size and each dendrite tended to occupy a particular region of the perisomatic space with minimal overlap with other dendrites. Quantitative and qualitative analysis of the dendritic arbors of the labeled neurons showed they had an asymmetric distribution so that some regions of the perisomatic space contained more of the dendritic tree than others. Eleven of the thirteen reconstructed neurons had a larger percentage of the dendritic tree projecting into the medial portion of the perisomatic space. These results show that the dendritic arbors of macaque TCP neurons are not organized in a radially symmetric pattern as previously described and the asymmetric distribution of dendrites may be related to synaptic input. PMID- 8199854 TI - GABAergic and dopaminergic transmission in the brain of Roman high-avoidance and Roman low-avoidance rats. AB - The GABAergic and dopaminergic pathways in the central nervous system (CNS) play a pivotal role in the control of emotions and in the adaptive responses to stressful stimuli. The present study was aimed at characterizing a range of biochemical markers of GABA- and dopamine-mediated neurotransmission in the CNS of Roman high-avoidance (RHA/Verh) and Roman low-avoidance (RLA/Verh) rats, two psychogenetically selected lines that differ in their level of emotionality. The stimulatory effect of GABA on 36Cl- uptake was less pronounced in the cerebral cortex of RLA/Verh rats as compared to RHA/Verh rats, whereas no line-related changes were detected in [3H]GABA and [3H]flunitrazepam binding. On the other hand, the density of D1 dopamine receptors labeled with [3H]SCH 23390 was lower in the nucleus accumbens of RLA/Verh rats as compared to their RHA/Verh counterparts, whilst no line-dependent changes were observed in the binding parameters of D1 dopamine receptors in the striatum, amygdala, and prefrontal cortex. These biochemical differences may contribute to the distinct emotionality and responsiveness to the effects of psychoactive drugs of RHA/Verh and RLA/Verh rats. PMID- 8199855 TI - Cholera toxin-induced Gs alpha down-regulation in neural tissue: studies on the pineal gland. AB - Cholera toxin (CT) treatment (50 micrograms/ml) was used to down regulate the alpha subunit of the stimulatory guanine nucleotide binding protein (Gs alpha) in pineal glands in organ culture, as has been seen in non-neural tissue. A 15 h treatment reduces Gs alpha by approximately 75% as measured using semi quantitative Western blot technology. In contrast, this treatment does not alter the abundance of G beta, Gi alpha or Go alpha. This effect on Gs alpha was still apparent following a 36-h washout period. The 48-h CT treatment increased cyclic AMP accumulation 10- to 17-fold but blocked the norepinephrine (NE)-induced increase in cyclic AMP accumulation, presumably reflecting the loss of Gs alpha. This treatment did not, however, inhibit protein synthesis or stimulation of arylalkylamine N-acetyltransferase (NAT) activity produced by treatment with either DB-cyclic AMP (N6,2'-O-dibutyryl adenosine 3',5' monophosphate) or 8 Br cyclic AMP, stable cyclic AMP derivatives. This indicates that a 48-h CT treatment was not generally toxic. In contrast, this treatment blocked subsequent CT stimulation of NAT. The effects of CT treatment on the adrenergic stimulation of NAT was examined using treatments which selectively produced alpha- or beta adrenergic stimulation. alpha 1-Adrenergic activation of the pineal gland elevates [Ca2+]i, which potentiates effects of cyclic AMP; in these studies the response to alpha-adrenergic activation was markedly increased in 48 h CT-treated glands, reflecting Ca2+ potentiation of the effects of elevated levels of cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199856 TI - Spatial, movement- and reward-sensitive discharge by medial ventral striatum neurons of rats. AB - Previous behavioral and acute electrophysiological data have lead researchers to speculate that the nucleus accumbens integrates limbic, reward and motor information. The present study examined the behavioral correlates to single unit activity of the nucleus accumbens and surrounding ventral striatum as a means of evaluating the integrative functioning of this region in an awake animal. Medial ventral striatum (mVS) activity was recorded as rats completed multiple trials on an eight arm radial maze. Neuronal activity was found to correlate with spatial, reward- and movement-related behavioral conditions. While the majority of cells demonstrated correlates of a single type (i.e. either spatial or reward correlates), 6 cells encoded multiple correlates of different types (i.e. spatial and reward correlates). The data suggests that this integrative process can be active both at the level of the individual neuron, and at the structural level. These results are consistent with the hypothesis that the mVS integrates spatial and reward-related information, which in turn influences voluntary motor output structures in order to achieve accurate navigational behavior. PMID- 8199857 TI - Differential neuronal responses to angiotensin III from the subfornical organ of normotensive and spontaneously hypertensive rats. AB - We previously reported that chronic central administration of angiotensin III (AIII) fails to produce sustained drinking behavior in spontaneously hypertensive rats (SHR), possibly because of the development of early desensitization of the angiotensin receptors. The present study extended these findings to the cellular level, using brain-slice preparation from Wistar-Kyoto rats (WKY) and SHR, in conjunction with single-neuron recording in the subfornical organ (SFO), a target site for angiotensin II-induced drinking. We found that a majority of the SFO neurons studied (13/18 in WKY, 20/28 in SHR) responded in a dose-related manner to AIII, given in the range of 10(-6)-10(-5) M. This excitation was receptor specific, since it was reversed by Ile7-AIII (10(-4)-10(-3) M), the selective AIII antagonist. Bestatin (10(-5)-10(-4) M), an aminopeptidase B inhibitor, did not discernibly affect basal spike frequency when delivered alone. Nevertheless, given in combination with the heptapeptide, bestatin reduced the intensity and duration of SFO neuronal response in WKY to the higher dose (10(-5) M), and in SHR to both doses (10(-6) or 10(-5) M), of AIII. These data suggest that the SFO may also be a central site of action for AIII. Moreover, prolonging the action of AIII by protecting it from being metabolized with bestatin may produce desensitization of the angiotensin receptors on SFO neurons. This was particularly so in the SHR, which are thought to be defective in the degradation of the heptapeptide in the brain. PMID- 8199858 TI - Methamphetamine-induced decrease in neural glucocorticoid receptors: relationship to monoamine levels. AB - Methamphetamine (MA) is a potent psychostimulant drug which is neurotoxic to dopamine (DA) and serotonin (5-HT) neurons. It has been previously reported that acute MA administration to adrenalectomized rats produced large dose-related decreases in hippocampal and striatal glucocorticoid receptors (GR). The present study was designed to determine if MA could decrease neural and peripheral GR when administered to adrenal-intact rats using a neurotoxic dosing regimen which produces depletions of brain DA and 5-HT levels. MA (0, 6.25, 12.5 and 25 mg/kg) was administered to adrenal-intact rats every 2 h for a total of 4 doses. Rats were adrenalectomized (ADX) 6 days later and subsequently sacrificed 24 h later. GR and mineralocorticoid receptors (MR) were measured using radioligand binding assays. Tissue levels of 5-HT and DA were measured in order to confirm the neurotoxic effects of MA and also to relate corticosteroid receptor levels to monoamine concentrations. MA produced dose-related decreases in GR levels in the hippocampus, striatum, frontal cortex and hypothalamus. Hippocampal MR were not affected by MA. 5-HT was also decreased in all of these same 4 brain regions, whereas DA was significantly decreased only in the striatum. MA did not decrease GR in cerebellum and similarly had no effect on DA and 5-HT in this region. MA also did not decrease GR or 5-HT levels in the spleen. These results demonstrate that MA produces a decrease in GR in a variety of brain areas, which is related primarily to 5-HT depletions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199859 TI - The habituation of brainstem catecholaminergic groups to chronic daily restraint stress is stress specific like that of the hypothalamo-pituitary-adrenal axis. AB - It has previously been shown that immobilization and ether stress induce activation of the hypothalamo-pituitary-adrenal (HPA) axis and that this activation occurs subsequent to activation of brain stem catecholaminergic neurones. In the present study we have investigated whether the brain stem catecholaminergic (CA) neurons show habituation to chronic daily intermittent exposure to the same restraint stress comparable to that of the HPA axis. The level of activity of the brainstem CA groups was estimated by measurement in tissue punches of content of 3,4-dihydroxyphenylacetic acid (DOPAC), a side metabolite of noradrenaline and adrenaline biosynthesis which has been shown to be a reliable index of the stress-induced activation of the CA groups. The level of activity of the HPA axis was determined by measurement of plasma corticosterone and adrenocorticotropic hormone (ACTH) levels. The animals were submitted to a 15 min restraint stress daily. They were sacrificed at the end of the stress session on day 3, 5 and 10. The ACTH response to the acute restraint stress whilst unchanged on day 3 was significantly decreased on day 5 (-54%) and day 10 (-70%) compared to the response in naive rats. The approximately twofold increase in DOPAC level induced by acute restraint stress in the so-called CA medullary group A1/C1 of naive rats was reduced in daily restraint rats on day 5 (-22%) and day 10 (-30%) but was unchanged on day 3. A small (-20%) decrease of the stress-induced DOPAC response in the A2/C2 CA group and locus coeruleus was also observed on day 10.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199860 TI - Aromatase-immunoreactivity is localised specifically in neurones in the developing mouse hypothalamus and cortex. AB - Local formation of oestrogens from androgens by aromatase cytochrome P-450 within brain cells is crucial for the sexual differentiation of the mammalian CNS. Aromatase activity has been detected in several brain regions of the developing rodent brain. In the present study, we used a mouse-specific, peptide-generated, polyclonal aromatase antibody to determine whether neurones and/or glial cells in the developing brain are involved in androgen aromatization and if aromatase immunoreactive (Arom-IR) cells exhibit a sex-specific distribution and regional specific morphological characteristics. For these experiments, gender-specific cell cultures were prepared from embryonic day 15 mouse hypothalamus and cortex. Specificity of the immunoreaction was confirmed by Western-blot analysis and by inhibition of aromatase activity using tissue homogenates from mouse ovaries and male newborn hypothalamus and from male hypothalamic cultures with known aromatase activity, respectively. Arom-IR cells were found in both hypothalamic and cortical cultures. Double-labeling experiments revealed that Arom-IR cells co stained only for the neuronal marker MAP II, but never for glial markers. Therefore aromatase immunoreactivity is specifically neuronal. Regional differences in the morphology of Arom-IR neurones were observed between both brain regions. In hypothalamic cultures, IR-neurones represented a heterologous population of phenotypes (magnocellular, small bipolar and multipolar neurones with long processes showing varicose-like structures or without processes). Cortical Arom-IR neurones were always oval in shape with short or no IR processes. Sexual dimorphisms in numbers of Arom-IR neurones were found in the hypothalamus with significantly higher cell numbers in male cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199861 TI - Cell death in primary cultures of mouse neurons and astrocytes during exposure to and 'recovery' from hypoxia, substrate deprivation and simulated ischemia. AB - Effects of hypoxia, substrate deprivation and simulated ischemia (combined hypoxia and substrate deprivation) on cell survival during the insult itself and during a 24 h 'recovery' period were studied in primary cultures of mouse astrocytes and in cerebral cortical neuronal-astrocytic co-cultures. Cell death was determined by release of the cytosolic high molecular enzyme lactate dehydrogenase (LDH) as well as morphologically (retention of staining with rhodamine 123 and lack of staining with propidium iodide as an indicator of live cells). Glutamate concentrations were measured in the incubation media at the end of the metabolic insults. Astrocytes were very resistant to hypoxia, but less so to simulated ischemia; under both conditions the glutamate concentrations in the media remained low. Cerebral cortical neurons were almost equally susceptible to damage by hypoxia and by simulated ischemia, although hypoxia had a faster deleterious effects on some of the neurons and simulated ischemia during a long term insult (9 h) killed all neurons, whereas a non-negligible neuronal subpopulation survived 9 h of hypoxia. Neuronal cell death after long-term hypoxia (but not after simulated ischemia) was correlated with high concentrations of glutamate in the incubation media. After certain insults, most notably relatively short lasting simulated ischemia (3 h) in neurons (which caused no increased cell death during the insult), there was a large release of LDH during the 'recovery' period. PMID- 8199862 TI - Functional characterization of the rat GAP-43 promoter. AB - GAP-43 is a highly conserved neuronal protein whose expression is spatially and temporally regulated. Because this regulation may occur, at least in part, at the level of transcription, we have begun to characterize the regions upstream of the GAP-43 transcription unit which direct its neuronal-specific expression. Functional analyses of GAP-43 promoter-reporter constructs have been performed in stably transfected cell lines, including PC12, C6 and RAT2. These data indicate that as little as 600 bp of GAP-43 5'-flanking DNA sequence directs the expression in a neuronal-specific manner. A shorter construct containing 230 bp of 5'-flanking DNA sequence defines a GAP-43 minimal promoter that is active in both neuronal and glial but not in non-neural cell lines. An upstream region, previously shown by other investigators to have promoter activity, was able to stimulate transcription when linked to the downstream minimal promoter. However, this upstream region was by itself unable to direct transcription of the reporting gene. In addition, we have demonstrated that two polypurine tracts within the 5'-flanking DNA sequence of the GAP-43 gene adopt a non-duplex configuration in plasmids, and, when studied in the context of chromosomal integration, these regions have a stimulatory effect on transcription. PMID- 8199863 TI - Glucose transporter 2 (GLUT 2): expression in specific brain nuclei. AB - In the brain, certain neurons appear to be sensitive to changes in local and/or plasma glucose concentration. The alterations in the electrical activity of these neurons probably depend on the existence of 'glucose sensors', which may be one of the glucose transporters described so far. Because of suitable kinetic properties, we hypothesized that the glucose transporter 2 (GLUT 2) may well constitute one of the cerebral 'glucose sensors'. In this study, it was demonstrated, using the polymerase chain reaction, that GLUT 2 mRNAs are present in a limited number of brain nuclei, including the nucleus tractus solitarius, the motor nucleus of the vagus, the paraventricular hypothalamic nucleus, the lateral hypothalamic area, the arcuate nucleus and the olfactory bulbs. These localizations were confirmed by immunocytochemistry, but the cerebral distribution of GLUT 2-like immunoreactivity was far larger than initially expected. Furthermore, electron microscopic observations showed that, within the regions examined, GLUT 2 was localized to a restricted population of astrocytes. The localization of GLUT 2 in regions previously connected with feeding behavior supports an indirect role for GLUT 2 in 'glucose sensing' in these specific cerebral structures. PMID- 8199865 TI - Regional differences in testosterone effects on vasopressin receptors and on vasopressin immunoreactivity in intact and castrated Siberian hamsters. AB - Vasopressin binding sites were detected in the brain of the Siberian hamster, using [3H]vasopressin and a 125I-labelled linear vasopressin antagonist specific for V1 vasopressin receptors. In the ventromedial and premammillary nuclei, the density of the binding was lower in the females than in the males. The effect of castration and of testosterone replacement was assessed in males. Two distinct effects were observed. Orchidectomy diminished significantly the vasopressin binding in the ventromedial nucleus, an effect which was prevented by implantation of a mini-pump releasing testosterone. On the contrary, in the premammillary nucleus no significant differences were noticed following castration and testosterone treatment. In addition, vasopressin immunoreactivity was examined in males, in females and in castrated males. No sex differences were evident. However, in the bed nucleus of the stria terminalis and the lateral septal nucleus, castration decreased vasopressin immunoreactivity in either sex. This effect of castration was prevented by testosterone. Vasopressin immunoreactivity was detected neither in the ventromedial nor in the premammillary hypothalamic nuclei. Our observations suggest that, in adult Siberian hamster premammillary nucleus, the expression of vasopressin receptors is not controlled by gonadal steroids but is sex related and could be induced during fetal or early postnatal life. PMID- 8199864 TI - Modulation of light-induced C-Fos expression in the suprachiasmatic nuclei by 5 HT1A receptor agonists. AB - In previous studies, we showed that light-induced Fos protein expression in the ventrolateral SCN is markedly inhibited by the nonselective serotonergic, quipazine. The present experiments were undertaken to characterize the effects of various serotonin (5-HT) receptor ligands on photic signalling in the SCN. The extent of expression of light-induced Fos-like immunoreactivity (Fos-LI) in the SCN was used as a marker for this response. Exposure of hamsters to a light pulse delivered during the latter part of the dark phase (7 h after lights-off; LD 14:10) elicited an intense expression of Fos-LI in nuclei of cells situated principally in the ventrolateral region of the SCN. Pretreatment with an i.p. injection of the 5-HT1A receptor agonists, 8-OH-DPAT or buspirone, 30 min before the light pulse significantly inhibited the photic expression of Fos-LI (maximal suppression 45.7 +/- 8.1 and 43.0 +/- 1.3%, respectively, both P < 0.01 vs. vehicle controls). Treatment with the 5-HT1A receptor antagonist, NAN-190, administered 15 min before 8-OH-DPAT injection prevented the inhibitory effect of 8-OH-DPAT (100.9 +/- 6.0% vs. controls, P > 0.9). Pretreatment with the 5-HT1B receptor agonist, TFMPP, caused a small but significant suppression of Fos-LI (14.8 +/- 3.5% vs. controls, P < 0.05). In contrast to the significant 5-HT1 receptor agonist effects, pretreatment with 5-HT2 or 5-HT3 receptor agonists, alpha-methyl-5-HT and 1-phenylbiguanide had little suppressive effect on Fos-LI (7.9 +/- 2.1 and 13.0 +/- 5.0% suppression, respectively, both P > 0.1 vs. controls).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199866 TI - Enlargement of olivo-cerebellar microzones in the agranular cerebellum of adult rats. AB - Previous work on normal adult rat showed that the vibrissae project, through the climbing fiber (CF) system, onto the Purkinje cells (PCs) of the contralateral cerebellar hemivermis of lobule VII. The highly elaborated CF projections from a given row of vibrissae delimit a narrow parasagittal zone which can be regarded as a functional olivo-cerebellar microzone. Interestingly, the adult one-to-one relationship between PCs and CFs is preceded by a transient phase during which each PC receives synaptic inputs from several CF collaterals which will be eliminated but one, when granule cells begin to establish synapses on PCs. Therefore, the question arose as to whether this synaptic elimination process could participate in the refinement of the topographical organization of CF projections and could contribute to the formation of such precise peripheral maps onto the cerebellum. In the present study, the topographical map of the CF mediated projection of mystacial vibrissae onto the vermal PCs of lobule VII was determined in adult rats whose cerebellar PCs remain polyinnervated by olivary CFs due to degranulation by postnatal X-irradiation. Using intracellular recordings, we examined the responsiveness of PCs in lobule VII during mechanical stimulation of the 3rd row of contralateral vibrissae, and positioned cells responding to the stimulation on an averaged planar map of lobule VII. Comparison of the results to those obtained in our previous work on normal rats showed that the activated cells were more numerous and more diffusely distributed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199867 TI - Lesions of the pedunculopontine tegmental nucleus block drug-induced reinforcement but not amphetamine-induced locomotion. AB - It has been proposed that the positive reinforcing and motor stimulating effects of drugs involve the activation of a common neural substrate. Reinforcing effects of food, drugs and brain stimulation are blocked by lesions of the pedunculopontine tegmental nucleus (PPTg), which is a component of the mesencephalic locomotor region. This has suggested that the PPTg may be involved in both positive reinforcement and forward locomotion. In four separate experiments, rats were prepared with NMDA (0.5 microliters of 0.1 M solution) or sham lesions of the PPTg. Animals in the first two experiments were tested for the development of a conditioned place preference (CPP) to morphine (2 mg/kg x 3 pairings) or amphetamine (1.5 mg/kg x 3 pairings). Ten days later, spontaneous motor activity (SMA) was assessed in these animals following a subcutaneous injection of saline or amphetamine (1.5 mg/kg). In two further experiments, drug naive lesioned and control animals were tested for SMA only (saline or 1.5 mg/kg amphetamine in Experiment 3, and saline, 0.5 mg/kg, or 3 mg/kg amphetamine in Experiment 4). Lesions of the PPTg blocked the development of a CPP to both morphine and amphetamine. In contrast, lesions had no effect on saline or amphetamine-stimulated SMA. The PPTg, therefore, appears to be involved in the reinforcing effects of amphetamine and morphine, but is not necessary for the expression of amphetamine-induced activity. PMID- 8199868 TI - The septum and amygdala differentially mediate the anxiolytic effects of benzodiazepines. AB - Microinfusions of a benzodiazepine anxiolytic (midazolam) into the septum or the amygdala suppressed different fear reactions in two tests of rat "anxiety". Septal infusions increased open-arm activity in the plus-maze test and decreased burying behavior in the shock-probe test whereas amygdaloid infusions produced neither of these antianxiety effects. Amygdaloid infusions, however, dramatically impaired shock-probe avoidance, an antianxiety effect not produced by the septal infusions. Infusions of the benzodiazepine receptor antagonist Ro 15-1788 (flumazenil) blocked each of these specific, anti-fear effects of midazolam without producing intrinsic effects by itself. These results suggest that benzodiazepine receptor systems within the amygdala and the septum differentially mediate specific fear reactions. PMID- 8199869 TI - The effect of chronic imipramine administration on the densities of 5-HT1A and 5 HT2 receptors and the abundances of 5-HT receptor and transporter mRNA in the cortex, hippocampus and dorsal raphe of three strains of rat. AB - We have recently demonstrated that the LEW/N rat contains lower concentrations of cortical and hippocampal 5-HT1A receptors compared with the F344/N and out-bred HSD rats. To further characterize these strains, we investigated the effect of chronic (8 wk) imipramine administration (5 mg/kg/day) on 5-HT1A and 5-HT2 receptor densities and mRNA in the cortex and hippocampus and 5-HT transporter mRNA in the dorsal raphe of LEW/N, HSD, and F344/N rats, using quantitative autoradiography and in situ hybridization histochemistry. After imipramine treatment, a significant increase in the levels of hippocampal 5-HT1A receptors, but not mRNA, was observed in LEW/N rats while the abundance of hippocampal 5 HT1A receptor mRNA, but not 5-HT1A receptor densities, decreased in F344/N rats. Cortical and hippocampal 5-HT2 receptor densities, but not mRNA, significantly decreased after imipramine administration in all three strains. Finally, 5-HT1A receptor densities and the abundance of mRNAs encoding the 5-HT1A receptor and 5 HT transporter in the dorsal raphe remained unaltered after imipramine administration in all three strains. The effects of imipramine on the levels of cortical and hippocampal 5-HT1A and 5-HT2 receptors and their transcripts, therefore, appear to be strain-dependent. The implications of these findings are discussed. PMID- 8199870 TI - The effect of 5-HT3 receptor antagonists on the morphine-induced excitation of A10 dopamine cells: electrophysiological studies. AB - In extracellular recordings from chloral hydrate anesthetized rats the 5-HT3 antagonist, BRL 46470A, failed to prevent or reverse the increase in dopamine cell firing rate produced by systemic or iontophoretically applied morphine. A second 5-HT3 antagonist, tropesitron, was similarly found to be ineffective in antagonizing the effects of systemic morphine. These results suggest that previous microdialysis reports that 5-HT3 antagonists can prevent the increase in extracellular dopamine levels in the nucleus accumbens produced by morphine are not due to an action of these compounds in suppressing the excitatory effects of morphine on A10 dopamine cell firing rate. PMID- 8199871 TI - Calbindin-like immunoreactivity in epithelial cells of the newborn and adult human vomeronasal organ. AB - The vomeronasal organs (VNOs) of two humans, a male neonate and a female adult, were examined for immunolocalization of calbindin-D28k (calbindin) which has been immunolocalized to VNO receptor cells in other mammals. The present study demonstrates that epithelial cells within the VNOs of both subjects expressed calbindin-like immunoreactivity. These results suggest that human VNO epithelial cells of both genders express calbindin during development and in the adult. PMID- 8199872 TI - Reduction of 1-methyl 1,2,3,4-tetrahydroisoquinoline level in substantia nigra of the aged rat. AB - The compounds 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4 tetrahydroisoquinoline (1-MeTIQ) are endogenous in humans and rats. Whereas TIQ seems to have neurotoxicity, 1-MeTIQ has been described as having a protective effect. In this paper, we report the concentration of TIQ and 1-MeTIQ in two areas especially influenced by aging and Parkinson's disease, the substantia nigra (SN) and striatum (ST), of the rat at different ages. 1-MeTIQ and TIQ were detected in both structures using gas chromatography-mass spectrometry with the higher content of both being in the SN. During the aging process there is a significant decrease (50%) in 1-MeTIQ levels in the SN, but TIQ levels did not change significantly in either of the studied regions. PMID- 8199873 TI - Thyrotropin-releasing hormone- and GABA-like immunoreactivity coexist in neurons in the dorsal horn of the rat spinal cord. AB - In order to determine which types of neuron in spinal dorsal horn contain the peptide TRH, pre-embedding immunocytochemistry with antiserum to TRH was combined with post-embedding detection of GABA- and glycine-like immunoreactivity. The majority (88/101) of TRH-immunoreactive neurons were also GABA-immunoreactive, but none were glycine-immunoreactive. This suggests that TRH is mainly present in inhibitory interneurons which release GABA but not glycine, and provides further evidence that there are functional differences between those GABAergic neurons in the superficial dorsal horn that contain glycine, and those that do not. PMID- 8199874 TI - Antiepileptogenic and anticonvulsant effects of NBQX, a selective AMPA receptor antagonist, in the rat kindling model of epilepsy. AB - To investigate the role of non-NMDA receptors in epileptic seizures, we examined the antiepileptogenic and anticonvulsant effects of NBQX (2,3-dihydroxy-6-nitro-7 sulfamoyl-benzo(F)-quinoxaline), a potent and selective AMPA receptor antagonist, in the rat kindling model. Systemic administration of 10-40 mg/kg NBQX significantly and dose dependently suppressed previously kindled seizures from the amygdala (AM), assessed in terms of the motor seizure stage and afterdischarge (AD) duration. The maximal effects were observed at 0.5-1 h after drug injection. When the intensity of electrical stimulation was increased to twice the generalized seizure-triggering threshold (GST), the anticonvulsant effects of NBQX on AM-kindled seizures were not reversed, suggesting that the effects were not due to non-specific elevation of the GST. In contrast to AM kindled seizures, 20-40 mg/kg NBQX significantly suppressed only the motor seizure stage without reducing the AD duration of previously hippocampal-kindled seizures. Daily administration of 15 or 30 mg/kg NBQX prior to each electrical stimulation of the AM markedly and significantly suppressed the development of kindling. During drug sessions, the growth of the AD duration was blocked almost completely, while the waveform of ADs became more complex. These results indicate that NBQX has potent antiepileptogenic and anticonvulsant actions on kindling, at least from the AM and that non-NMDA receptors have an important role in seizure propagation. PMID- 8199875 TI - Sex differences in the anticonvulsant efficacy of phenytoin in amygdala-kindled rats. AB - The anticonvulsant effects of phenytoin were compared in female and male amygdala kindled rats. Phenytoin was administered at a dosage of 75 mg/kg i.p. and the threshold for induction of amygdaloid afterdischarges (ADT) was determined 1 h after drug application. This ADT determination was repeated three times in each animal at intervals of one week. For control of drug absorption, phenytoin was determined in plasma in each of the four drug trials. In a total of 104 drug trials in females and 78 trials in males, anticonvulsant responses (i.e. increases in ADT above pre-drug control) were found in 76% of trials in female rats but only 42% of trials in male rats, the difference being highly significant. Consistent responses to phenytoin (i.e. ADT increases of more than 100% in four consecutive trials) were found in 31% of the female rats but only 6% of the male rats. Twenty-four percent of the females but 58% of the males never responded to phenytoin with an ADT increase. About 50% of both female and male rats showed variable responses. Although plasma levels of phenytoin were slightly lower in male than in female rats, there was no significant difference in drug levels between phenytoin responders and nonresponders in both sexes, indicating that the sex difference in anticonvulsant efficacy of phenytoin was not due to differences in drug pharmacokinetics. This was substantiated by the finding that in experiments with anticonvulsant response, the phenytoin-induced ADT increases were similar in male and female rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199876 TI - Effects of kainate-induced seizures on cerebral metabolism: a combined 1H and 31P NMR study in rat. AB - The cerebral metabolic changes elicited by kainate-induced seizures in the rat were investigated by in vivo combined NMR spectroscopy of 31P and 1H. Systemic injection of kainate induced no significant changes in cerebral ATP or PCr levels during up to 90 min of continuous, generalised seizures, and the cerebral 31P spectra showed only a transient mild cerebral acidosis 30 min after kainate administration. In parallel with the changes in intracellular cerebral pH, the 1H spectra showed a significant increase in lactate, which remained elevated throughout the seizures. These findings indicate that oxidative metabolism does not completely match the increased glycolysis during seizures though the energy homeostasis is maintained. This suggests that oxidative metabolism has a limited capacity to satisfy the brain's energy needs during the kainate-induced seizures, but that the different pathways of energy production in the brain cells can overcome this limitation. Thus the brain damage associated with this experimental model of epilepsy is not due to extended major failure of the energy supply. PMID- 8199877 TI - Cholecystokinin octapeptide (CCK-8) injected into a cerebral ventricle induces a fever-like thermoregulatory response mediated by type B CCK-receptors in the rat. AB - In conscious female Wistar rats with chronic lateral cerebroventricular cannula, the thermoregulatory effects of CCK-8, ceruletide and prostaglandin E1 (PGE1) were studied. In addition, the possible involvement of type A or type B receptors of CCK-8 in thermoregulatory effects of PGE1 and CCK-8 was also investigated. In the normothermic rat an intracerebroventricular (i.c.v.) injection of CCK-8 or ceruletide induced a thermogenic response with tail-skin vasoconstriction and a resulting rise in colonic temperature (Tc). There was a significant negative correlation between the starting level of Tc and the extent of rise in Tc following an i.c.v. administration of PGE1, CCK-8 or ceruletide. Subcutaneously injected CCK-8 caused decreases in Tc in a cool ambient temperature as also described by others. The fever-like response to i.c.v. injected CCK-8 was attenuated by a CCK type B receptor blocker, but not by a CCK type A receptor blocker. Conversely, the hypothermic response to peripherally administered CCK-8 was attenuated by a type A receptor blocker, but not by a type B receptor blocker. Neither of these CCK-receptor blockers influenced the fever caused by an i.c.v. injection of PGE1. It is concluded that in normothermic rats the thermogenic response observed after i.c.v. injection of CCK-8 and ceruletide is the most likely central thermoregulatory change mediated by CCK type B receptors, while the well-known hypothermic response observed after peripheral injection of these peptides might also be explained by their direct effect on variables influencing some of the thermoregulatory effector mechanisms at the periphery. PMID- 8199878 TI - The effects of systemic glucose concentration on brain metabolism following repeated brain ischemia. AB - Since systemic glucose concentration is an important determinant of ischemic brain metabolism in neonates, we sought to determine if the systemic glucose concentration influences brain metabolic alterations following repeated partial ischemia. A group of hyperglycemic piglets (n = 12) were compared to a group of modestly hypoglycemic piglets (n = 12) using in vivo 2H and 31P magnetic resonance spectroscopy to simultaneously measure cerebral blood flow and phosphorylated metabolites before, during and 30 min after two 10-min episodes of ischemia (i.e. Recovery 1 and 2). For both groups, beta-ATP levels at Recovery 1 and 2 were lower than Control (91 +/- 11 and 83 +/- 15% of Control, respectively for both groups combined, P = 0.002 vs Control). Inorganic phosphorus was elevated in hyperglycemic piglets at Recovery 1 and 2 (117 +/- 15 and 118 +/- 10% of Control). In contrast, in modestly hypoglycemic piglets inorganic phosphorus progressively rose from Recovery 1 (131 +/- 24% of Control) to Recovery 2 (149 +/ 37% of Control), and differed from the hyperglycemic group (P = 0.02). These changes did not correlate with post-ischemic cerebral blood flow, cerebral O2 delivery or cerebral glucose delivery. In both groups phosphocreatine and intracellular pH returned to Control values during Recovery 1 and 2. The progressive increase in inorganic phosphorus post-ischemia in hypoglycemic piglets suggests that modest hypoglycemia during and following repeated partial ischemia adversely affects immediate brain metabolic recovery. PMID- 8199879 TI - Quantitative autoradiography of 5-HT1D and 5-HT1E binding sites labelled by [3H]5 HT, in frontal cortex and the hippocampal region of the human brain. AB - In human cortex and hippocampus area, [3H]5-HT (5 nM) labels 5-HT1A, 5-HT1D and 5 HT1E sites. After masking 5-HT1A receptors by 0.1 microM 8-OH-DPAT, the binding displaced by 0.1 microM 5-CT presumably represented 5-HT1D sites and the remaining binding 5-HT1E sites. In frontal cortex, 5-HT1A receptors represented the main binding in layers II and VI and a lower fraction in other layers. 5-HT1D and 5-HT1E sites, were more homogeneously distributed in layers II to VI (21-34% of specific [3H]5-HT binding). 5-HT1E sites were of similar affinities (KD close to 6-8 nM) in the cortical layers II to VI. In CA1 field of hippocampus, (pyramidal layer, stratum radiatum, molecular layer), CA2 and dentate gyrus, 5 HT1A receptors represented the major fraction, 5-HT1D sites a significant fraction and 5-HT1E a minor fraction of the specific [3H]5-HT binding. In CA3-CA4 fields, 5-HT1A receptors were less densely present, 5-HT1D sites were predominant and 5-HT1E sites represented a significant fraction (27%). The highest densities of 5-HT1E sites have been measured in subiculum, where 5-HT1A, 5-HT1D and 5-HT1E binding sites were equally represented and in entorhinal cortex where 5-HT1E sites represented the major binding in layer III. They were also present in layers II and IV (29 and 24%) and, to a lesser extent, in layers V and VI. 5-HT1A sites were predominant in layer VI, II and V and were less abundant in other layers. 5-HT1D were homogeneously present in layers II, III, IV and were present in low amounts in other layers. No 5-HT1E were detected in choroid plexus, where [3H]5-HT was dramatically reduced by mesulergine (5-HT2C receptors). No significant displacement of [3H]5-HT by mesulergine was measured in other structures. PMID- 8199880 TI - Effect of different dietary supplemental fats and oils on the tissue fatty acid composition and growth of female broilers. AB - 1. A study was undertaken to examine the effect of supplementation of diets with fats of different chain length and degree of unsaturation on the performance, carcase characteristics and tissue fatty acid composition of broilers. 2. Three hundred and sixty 19-day-old female broilers were fed on diets containing supplemental fat/oil (50 g/kg) in the form of beef tallow (BT) (diet T-T), soyabean oil (SBO) (diet S-S), rapeseed oil (RSO) (diet R-R), marine oil (MO) (diet M-M) or binary mixtures (0.5:0.5 w/w) of these lipids (diets T-S, T-R, T-M, S-R, S-M, and R-M) to 54 d of age. Food intake, live weight, plucked weight and the lipid concentration and fatty acid composition of abdominal fat pad, liver and breast muscle were measured. 3. Food intake, plucked weight and live weight were greatest for diet T-T and lowest for diet R-R. Food conversion ratio was poorest for birds fed on diets containing BT. Lipid concentration in abdominal fat pad was significantly higher in birds fed on diets containing SBO. Liver lipid concentration was significantly reduced by diets containing RSO. 4. Abdominal fat pad fatty acid profile was most readily altered by dietary fatty acids. There was a strong correlation between dietary fatty acid composition and tissue fatty acid composition for all fatty acids except C14:0, C20:0, C20: 2n-6 and C20: 4n-6. The tissue P/S ratio ranged from 0.40 for diet T-T to 1.40 for diet S-S. The n-6/n-3 ratio was significantly increased by the inclusion of SBO and decreased by the inclusion of MO. 5. Liver fatty acid profile was least modified by dietary fatty acids. There was an inverse relationship between liver and dietary C20:4n-6 concentration. Tissue C18:2n-6 and C20:4n-6 were highly correlated, suggesting significant interconversion by delta-6 desaturase in this tissue. The n-6/n-3 ratio was significantly increased by inclusion of SBO and significantly decreased by the inclusion of MO. 6. In breast muscle MO-based diets increased the proportion of n-3 PUFA at the expense of n-6 PUFA. The tissue concentrations of C18:1n-9, C18:2n-6, C20:1n-9, C20:5n-3, C22:5n-3 and C22:6n-3 were strongly correlated with dietary fatty acid composition. Muscle and diet P/S and n-6/n-3 ratios were highly correlated. PMID- 8199881 TI - True metabolisable energy values of some feedingstuffs. AB - 1. The apparent metabolisable energy (AME) and the true metabolisable energy (TME) contents of some feedingstuffs were determined with cockerels. The test materials consisted of feed-grade lentil, lentil bran and wild vetch seed. 2. The average values of nitrogen lost, endogenous energy losses (EEL) and endogenous energy losses corrected to zero-nitrogen balance (EELN) were found to be 1.18 g, 62.13 kJ and 21.51 kJ/bird/48h, respectively, from adult cockerels given an energy supply as 50 g glucose during starvation. 3. The nitrogen-corrected apparent metabolisable energy (AME(N)) values for feed-grade lentil, lentil bran and wild vetch seed, respectively, were 6.84, 3.05 and 14.31 kJ/g dry matter. The nitrogen-corrected true metabolisable energy (TMEN) values for the respective feedingstuffs were 7.44, 3.65 and 14.90 kJ/g dry matter. PMID- 8199882 TI - Effect of growth promoters on monensin toxicity in broiler chicks. AB - 1. An experiment was carried out with male broiler chicks to evaluate the combined effect of monensin (150 mg/kg) and the growth promoters (GPs) Zn bacitracin (BAC, 50 mg/kg), virginiamycin (VIR, 25 mg/kg) and avoparcin (AVO, 20 mg/kg) fed from 7 to 28 d of age on performance, utilisation of dietary nutrients, yield of defeathered eviscerated carcases (DEC) and size of various organs. The effect of the GPs in the monensin-unsupplemented diets fed up to 49 d of age on performance and carcase was also determined. 2. Monensin significantly (P < 0.05) depressed food intake, weight gain and food efficiency from 7 to 28 d of age. None of the GPs was able to counteract these effects. However, AVO slightly ameliorated them. AVO also significantly increased food intake and improved gain and food efficiency during 7 to 28, but not 28 to 49 or 7 to 49 d of age. VIR and BAC did not affect performance in either age period. 3. Monensin did not affect the utilisation of dietary dry matter, fat or energy, but it significantly decreased nitrogen utilisation. AVO improved nitrogen and fat utilisation and increased dietary AME(n) content. AME(n) was also increased by VIR. The utilisation of these nutrients was not affected by the interactions between monensin and the GPs. 4. Monensin did not affect yield of the DEC or the relative liver size at 31 d of age. It significantly increased the relative length of the small intestine (SI) and decreased its specific weight. AVO significantly increased yield at 31, but not at 53 d of age. BAC and VIR did not affect this variable. AVO and VIR, but not BAC, at both age periods reduced, at times significantly, the size, length and specific weight of the SI. 5. Our conclusions: BAC, VIR and AVO do not counteract the toxic effect of monensin. The effect of GPs in improving performance decreases and even disappears with age, while their effect in reducing the size of the SI is still evident in 49-d-old birds. PMID- 8199883 TI - Comparison of energy metabolism during the growing period in quail lines selected for body weight. AB - 1. The present study was conducted to compare body weight, daily weight gain, relative growth rate, food intake, food conversion efficiency, abdominal fat weight, thyroid weight, plasma T4 concentration, body temperature, oxygen consumption, carbon dioxide production and heat production among three Japanese quail lines selected for body weight: a random bred line (RR) and lines for large (LL) or small (SS) body weight. 2. T4 concentration increased in the order SS, RR, LL in both sexes and did not vary significantly between sexes; the SS line had a significantly higher value than that of the LL line. 3. The body temperatures of SS, RR and LL lines were 42.45, 42.03 and 41.25 degrees C in males, and 42.7, 42.03 and 41.63 degrees C in females. 4. The oxygen consumptions of SS, RR and LL lines were 63.4, 46.0 and 43.8 ml/kgW0.75 min. in males, and 61.4, 44.8 and 37.2 in females. The value for SS was significantly higher than those of RR and LL lines in both sexes (P < 0.01). The carbon dioxide productions of SS, RR and LL lines were 31.8, 33.8 and 27.3 ml/kgW0.75 min. in males, and 31.2, 31.9 and 27.3 in females. In both sexes, that of the LL line was significantly lower than those of the SS and RR lines (P < 0.01). 6. The heat productions of SS, RR and LL lines were 1.178, 0.994 and 0.842 kJ/kgW0.75 min. in males, and 1.142, 0.879 and 0.736 in females. In both sexes, the heat production of the SS line was higher than those of the RR and LL lines (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8199884 TI - Pulsatility of plasma growth hormone and hepatic growth hormone receptor characteristics of broiler chickens divergently selected for abdominal fat content. AB - 1. Plasma growth hormone (GH) pulsatility and hepatic GH receptor characteristics were compared in experimental lines of meat-type chickens selected for high (HF) or low (LF) abdominal fat content. 2. Mean GH concentration, baseline and amplitude of pulses were slightly, but not significantly, greater in LF chickens. Length and frequency of pulses were similar. 3. LF chickens exhibited higher plasma triiodothyronine (T3) concentrations. This difference between genotypes disappeared when the diet was supplemented with 1 mg/kg T3. 4. Specific binding of GH to liver membranes was higher for the fat line but was depressed by T3 supplementation to the same level in both lines. No difference was observed between lines for affinity constants. 5. It is concluded that direct selection for leanness has a less pronounced, if any, effect on GH pulsatility as compared with selection for food conversion efficiency; therefore, different physiological mechanisms are triggered to achieve leanness. PMID- 8199885 TI - Effect of progesterone on ovulation in the hypophysectomised hen. AB - 1. One hundred and seven laying hens were hypophysectomised to clarify the relationship between hypophysectomy and the effect of progesterone (P4) on ovulation. 2. Hens were hypophysectomised at 6 intervals from 4.5 to 11.0 h before the expected time of ovulation. Ovulation occurred in the hens operated on from 4.5 to 7.3 h, but did not take place in birds operated on from 9.2 to 9.8 h before the expected time of ovulation. 3. When a single dose of P4 (2 mg/hen) was injected iv immediately after the removal of the anterior pituitary from 7.5 to 9.8 h before the expected time of ovulation, ovulation was induced. However, the percentage of hens responding decreased in proportion to the lapse of time between the hypophysectomy and the expected time of ovulation. No ovulation was induced in hens which were hypophysectomized and given P4 10.2 to 11.0 h before the expected time of ovulation. 4. It is suggested that ovulation is induced by P4 alone possibly in the absence of preovulatory gonadotrophins and that P4 acts directly on the ovary to induce follicle rupture. PMID- 8199886 TI - Inhibitory effect of penicillin on caecal urease activity in chickens fed on a low protein diet plus urea. AB - 1. The effects of dietary penicillin on the urease activities of small intestine, large intestine, caecum and their contents, liver and kidney in chickens fed a diet containing 5 g/kg protein plus urea were examined. 2. About 0.88 of the total urease activity determined was observed in intestinal contents, of which 0.95 of the activity was accounted for by caecal contents, 0.05 by colo-rectal contents and none by small intestinal contents. Intestinal tissues (caecum included), liver and kidney accounted for 0.03, 0.06 and 0.02, respectively, of the total urease activity. 3. Dietary penicillin decreased urease activity to 0.17 in caecal contents and to 0.05 in colo-rectal contents of the corresponding control values (P < 0.01). The urease activity of caecal tissue was lowered by penicillin to half that of control activity (P < 0.05) but none of the activities of other tissues were affected. 4. It is concluded that, even when the urease activity is stimulated by dietary urea, 20 mg/kg dietary penicillin can strikingly lower it in the caecum, where most of the urease activity in the chicken body is to be found. PMID- 8199887 TI - Effects of timing and size of daylength change on brown egg laying domestic hens: plasma luteinising hormone concentration and sexual maturity. AB - 1. Brown egg laying pullets were transferred from an 8-h photoperiod to an 8-, 10 , 13- or 16-h photoperiod at 6, 9, 12, 15, 18 or 20.3 weeks of age. Plasma luteinising hormone (LH) concentrations were measured at transfer and 7 and 14 d afterwards. 2. Significant increases in plasma LH occurred following light stimulations at 6, 9 and 12 weeks of age. 3. Changes in LH concentration 7 d after a light increase from 8 h to 8, 10, 13, 16 h were highly correlated with photoperiod length at 9 and 12 weeks of age. 4. Changes in LH were generally poorly correlated with age at sexual maturity, although the reduced influence on age at first egg of a light increase given close to sexual maturity was reflected in minimal LH responses at 18 and 20.3 weeks. PMID- 8199888 TI - Gordon Memorial Lecture. Problems and crusades: a history of poultry disease research in the United Kingdom. AB - 1. Poultry disease research in the UK began recognisably in the 1920s, in consequence of the development of a national poultry industry of economic importance. 2. Increasing disease problems during the 1930s revealed the need for more research, resulting notably in the growth of the Poultry Department of the Central Veterinary Laboratory and the establishment of Houghton Poultry Research Station. 3. Continued growth of the egg industry and the introduction of the broiler industry in the 1950s stimulated increased disease research, much of it publicly funded, during the following two decades. 4. Changing government attitudes to agricultural research in the 1980s brought about far-reaching changes to the funding, organisation, nature and amount of disease research conducted. Arrangements for such research continue to evolve. PMID- 8199889 TI - Crossbreeding effects for body weight and carcase traits in Pekin duck. AB - 1. Three sire lines of Pekin duck, three dam lines and 9 crosses between these two groups were tested in replicated tests from 1987 to 1991. Body weight at the age of 7 weeks (n = 5189), carcase percentage, percentage of abdominal fat and thickness of breast muscles were recorded (n = 1432 for carcase traits). 2. The data were analysed by linear models. All models contained the factors test and sex. When analysing only crosses, general and specific combining abilities (GCA and SCA respectively) were included as well as their interactions with the test. Using the complete data set (lines and crosses), direct genetic and heterotic effects were considered. 3. The factors test and sex were significant in both data sets for all traits. 4. For body weight, all genetic factors were significant. The average heterosis was 65 g +/- 9 g (2.2%); the highest observed heterosis was 7.7%. 5. For carcase percentage, the heterosis was always negative (up to -2.1%), whereas in abdominal fat, a desirable negative heterosis was observed only in one cross. No significant heterotic or combining ability effects were observed in the thickness of breast muscles. 6. Significant interactions between at least one genetic factor and test were found in all traits. 7. The relative importance of GCA and SCA, possible sources of confounding estimates of genetic effects, the importance of heterotic effects and genotype x environment interactions are discussed. PMID- 8199890 TI - Divergent selection for delayed-type wattle reaction of domestic fowls to BCG antigen. AB - 1. Two-way selection for delayed-type hypersensitivity wattle reaction (DWR) competence to BCG antigen was carried out over 4 generations, using a flock of White Leghorn chickens. DWR was measured by intradermal injection of BCG into the wattle of chickens. 2. Selection for DWR was effective. The generation means of average selection differential, selection response and realized heritability were 1.15 mm, 0.77 mm and 0.70 respectively. Correlated responses were found in body weight, egg weight and hatchability. In all of these traits, the L line (selected for low wattle reaction) showed higher values than the H line (high reaction). 3. Specific trends in gene frequencies were observed at the major histocompatibility B and alkaline phosphatase Akp loci. 4. Significant line differences were found in graft-versus-host reaction competence and Marek's disease resistance. In both characters, the L line was higher than the H line. No line differences were found in phytohaemagglutinin response, phagocytic activity or immune responses. PMID- 8199891 TI - Heritabilities for duration of fertility traits in brown Tsaiya female ducks (Anas platyrhynchos) by artificial insemination with pooled muscovy (Cairina moschata) semen. AB - 1. Fertility traits in 348 Brown Tsaiya female ducks were analysed following intergeneric crossbreeding by artificial insemination (AI) with pooled Muscovy semen. The females descended from 18 sires and 107 dams. At 50 weeks of age, the ducks were intra-vaginally inseminated once with 0.03 ml of pooled Muscovy semen. Subsequently eggs were collected for 15 d and set for incubation up to candling 10 d later. 2. Average fertility decreased from 87% at day 2 after AI to 53% at day 6 and less than 7% from day 10 onwards. 3. The best criterion of selection for duration of fertility seems to be the number of fertile eggs from 2nd day up to the 15th day after AI. Heritability estimates for this trait were hs2 = 0.29 +/- 0.18., hD2 = 0.38 +/- 0.22. PMID- 8199892 TI - Effects of divergent selection for body weight on three skeletal muscles characteristics in the chicken. AB - 1. Histochemical (fibre type distribution and areas) and biochemical (myosin isoforms) characteristics of three muscles, M. anterior latissimus dorsi, M. pectoralis major and M. sartorius, were compared among male chickens of two lines at 11 and 55 weeks of age. 2. The lines were derived from a divergent selection based on growth rate. Cockerels from the Fast Growing Line (FGL) were 2.3 times heavier than those from the Slow Growing Line (SGL) when 11 weeks old and 1.7 times at 55 weeks of age. The latter age was chosen as representative of the adult stage and the 11-week age because, at this time, FGL cocks weighed as much as SGL cockerels at 55 weeks. 3. At both ages, the two lines showed similar fibre type distributions, but the total number in the ALD muscle, and the size (cross sectional areas) of fibres in each muscle were higher in the FGL compared with the SGL (14.6% and 33% more at 11 and 55 weeks of age respectively in favour of the FGL birds). 4. The two lines displayed similar myosin isoform patterns when adult muscles were compared (55 weeks). They differed slightly at 11 weeks of age, muscle differentiation being completed only in the FGL. 5. Comparisons of the two lines at the same live weight (i.e. FGL cockerels at 11 weeks of age and SGL cockerels at 55 weeks) showed larger muscle fibres in the SGL and no difference in the isomyosin patterns. PMID- 8199893 TI - Relationship of decreased caecal urease activity by dietary penicillin to nitrogen utilisation in chickens fed on a low protein diet plus urea. AB - 1. The relationship of the decreased caecal urease activity by dietary penicillin to nitrogen utilisation was assessed in chickens fed a low protein diet plus urea. 2. Dietary penicillin at 20 and 100 mg/kg decreased anaerobic bacteria counts, urease activity and ammonia concentration in caecal contents (P < 0.05, except for ammonia in the case of the 100 mg/kg penicillin diet). 3. The 20 mg/kg penicillin diets significantly increased the excretion of urea and total nitrogen (P < 0.05) and decreased ammonia excretion, and significantly reduced nitrogen retention (P < 0.05). The 100 mg/kg penicillin diet also resulted in similar but not significant changes, which tended to be less than those by the 20 mg/kg penicillin diet. 4. Ammonia, urea, glutamine and uric acid concentrations in blood, liver and kidney were unchanged by dietary penicillin. 5. It is concluded that caecal ammonia production from urea was closely correlated with nitrogen utilisation in chickens fed a low protein diet plus urea. PMID- 8199894 TI - Energy and nitrogen metabolism and oxygen use by broilers susceptible to ascites and grown at three environmental temperatures. AB - 1. An experiment using respiration calorimetry was performed to examine the energy and nitrogen metabolism of 2 strains of male broilers grown at 3 environmental temperatures; the results were then related to the susceptibility of the strains to the ascites syndrome. 2. Broilers selected for food conversion efficiency were less responsive to environmental temperature than were broilers selected principally for increased weight gain. 3. The susceptibility to ascites of broilers selected for food conversion efficiency may be the result not of a genetic incapacity to use oxygen but of the ability of the bird to maintain growth rate in adverse thermal environments. PMID- 8199895 TI - Putting the anatomical doll controversy in perspective: an examination of the major uses and criticisms of the dolls in child sexual abuse evaluations. AB - Through an extensive review of guidelines and protocols on the use of anatomical dolls in sexual abuse evaluations, seven functional uses of the dolls were identified: Comforter, Icebreaker, Anatomical Model, Demonstration Aid, Memory Stimulus, Diagnostic Screen, and Diagnostic Test. These functional uses are discussed in light of several criticisms that have been raised about the use of anatomical dolls in sexual abuse evaluations. The relevancy of these criticisms is shown to vary greatly by doll use. As a result, the authors argue that any critique of anatomical dolls must consider the specific function the dolls serve in the evaluation. Although there seem to be widespread perceptions in both lay and professional circles that young children's behavior with the dolls is commonly used to make definitive diagnoses of sexual abuse (Diagnostic Test Use), such a use of the dolls was not endorsed by any of the guidelines reviewed and is open to significant criticism. The most common criticisms of the dolls, that they are overly suggestive to young, sexually naive children, is not supported by available research. Finally, the continued, informed use of anatomical dolls in sexual abuse evaluations of young children is strongly supported. PMID- 8199896 TI - Sexual fantasies, gender, and molestation history. AB - A total of 314 university students (107 males and 207 females) completed a questionnaire examining reports of childhood sexual abuse history and extent and type of adult sexual fantasies. Multivariate main effects of gender and abuse history were found, as well as a multivariate interaction between these variables. Males had more fantasies of forcing someone to have intercourse with them, participating in an orgy, and having sex with a stranger. Subjects with histories of sexual abuse had more sexual fantasies than their nonabused peers in four of five categories. Finally, sexually abused women reported more fantasies of being sexually forced than did women without sexual abuse histories or men regardless of molestation history. In several instances, fantasies correlated with especially early and extended abuse. PMID- 8199897 TI - Exploration of anatomical dolls by nonreferred preschool-aged children: comparisons by age, gender, race, and socioeconomic status. AB - The contributions of age, gender, race, and socioeconomic status (SES) to differences in nonreferred (i.e., presumably nonabused) preschool-aged children's interactions with anatomical dolls were explored. Significant age findings included a decrease with age in manual exploration, an increase in showing doll to-doll kissing and an increase in demonstrating suggestive intercourse between the dolls. Although 2-year-olds were active in undressing the dolls and exploring the genitals, anus, and breasts, no 2-year-old displayed any sexualized behaviors with the dolls. Six percent (6%) of the children demonstrated clear intercourse positioning. Only low SES black males, ages 4 and 5, demonstrated clear intercourse positioning when the interviewer was present in the room. However, such demonstrations were seen across gender and race and SES when the children were left alone with the dolls. The implications of the findings for evaluators who interview children using anatomical dolls are discussed. PMID- 8199898 TI - Punitive childhood experiences reported by young adults over a 10-year period. AB - Using a standardized questionnaire, descriptions of disciplinary childhood experiences were obtained from 11,660 university undergraduates over a 10-year period. Results indicated that there were no systematic changes in reports of physical discipline experienced by young adults over the decade sampled, suggesting the prevalence of physical abuse among predominately middle-income families is not evidencing any significant change. Additionally, regardless of whether their early childhood antedated or succeeded the growth in public attention to physical abuse, most young adults who reported severely punitive or injurious disciplinary events failed to categorize those experiences as abusive. The implications of the results are discussed in the context of efforts to raise public awareness of abuse and efforts to reduce possible transgenerational patterns of maltreatment. PMID- 8199899 TI - Perceptions of mothers' and fathers' abusive and supportive behaviors. AB - Young adults' perceptions of parenting behaviors were explored, specifically with regard to the issue of how perceptions may be affected by gender of parent, child, or observer. Ratings of psychologically (emotionally), physically, and sexually abusive behaviors and ratings of love/support, promotion of independence, and positive modeling/fairness were obtained for mothers and fathers as well as daughters and sons. When father was the referent, female subjects rated the behaviors as more emotionally, physically, and sexually abusive than male subjects did. When mother was the referent, gender of subject and gender of child interacted, with female subjects rating the behaviors as more abusive when done to sons than male subjects did. Male and female subjects agreed that behaviors representing love/support and fairness were highly supportive when done by fathers. When done by mothers, female subjects rated love/support behaviors as more supportive for sons than male subjects did. Results indicated that gender of parent, child, and observer may affect young adults' perceptions of parental abusiveness and supportiveness. PMID- 8199900 TI - Developmental issues in young children's learning of sexual abuse prevention concepts. AB - This research is an item analysis of a measure of knowledge of sexual abuse prevention concepts, the Children's Knowledge of Abuse Questionnaire (C.K.A.Q.), which was utilized in an evaluation of an elementary school program. The literature review highlights developmental theories that distinguish between children in Grades 1, 3, and 6 (N = 111). These theories may explain the obtained differences in children of various ages in learning core prevention concepts. The findings are of interest in three ways: inspection of differences in the ease with which the children of each age group responded to specific items even before seeing a prevention program; identification of items in which there was significant improvement after the children participated in the prevention program; and evidence to suggest that children of different ages responded differentially to certain prevention concepts. The implications for the development, presentation and evaluation of child abuse prevention programs are discussed. PMID- 8199901 TI - A conceptual framework for thinking about risk assessment and case management in child protective service. AB - The present paper presents a broad conceptual framework for examining methodological issues in risk assessment in child protective service work. The following issues are discussed: standards for determination of risk; types of data collected; sources of information; types of possible errors; incremental validity issues; cultural context of decision making; assessment of problem origins; selection of outcome goals and implementation strategies; and treatment monitoring and case closure decisions. Risk assessment procedures vary on a number of dimensions, and the task of comparing one procedure to another is quite complex. Clearly, techniques cannot be considered from one vantage point and must take into account the general purpose of the assessment, the specific types of decisions that are to be made, and for whom, by whom, and within what context the data is to be gathered and used. PMID- 8199902 TI - Maternal compliance to court-ordered assessment in cases of child maltreatment. AB - Parental compliance to court-ordered assessment was examined in 82 mothers whose children had been removed from the home due to child maltreatment. Compliant (n = 52) and Noncompliant (n = 30) mothers were compared on parental and psychosocial risk factors previously documented in child maltreatment research. The results indicate that noncompliant mothers tend to be younger, lead more transient lifestyles, show a greater degree of antisocial behavior, and experience more violence in their spousal relationships. The implications of these data for clinical and legal involvement with these families is discussed. PMID- 8199903 TI - Child sexual abuse by uncles: a risk assessment. AB - Using a sample of 982 mothers who reported on child care and living arrangements involving uncles, and case records documenting the sexual abuse of 171 children by 148 uncles, this study examined the ways uncles ordinarily become involved with children, the conditions under which that involvement becomes associated with sexual abuse, and the role gender plays in this dysfunction. Among the findings, it was noted that although aunts were responsible for 28 times more child care than uncles, uncles were responsible for 48 times more child sexual abuse. Although female children do not have more exposure to uncles than do males, they appeared four times more likely to be victimized. About 19% of the abusive uncles lived with the children they abused, and most of the remainder came into contact with them as child care providers or during overnight visits. Implications for practice are discussed. PMID- 8199904 TI - The prospective assessment of self-concept in neglectful and physically abusive low income mothers. AB - Maternal self-esteem has long been associated with the quality of maternal-child interactions and many assume that low self-esteem contributes to the cause of maltreatment. Assessments of the self-concepts of maltreating parents, however, have been done only after maltreatment has occurred. Prospective measurement of self-concept would help to clarify its role in the etiology of maltreatment. In this study, 471 pregnant women completed the Tennessee Self-Concept Scale (TSCS). State protective services' records were reviewed 3 years after these children were born. When records of the 459 women with a known live-born child were reviewed, 29 were found to have maltreated their children (neglect n = 22; physical abuse n = 11; four women found to have both neglected and abused their children). Neglectful mothers had lower scores on scales measuring overall self esteem, moral self-worth, personal and social adequacy, and perception of self worth in family relationships than matched nonreported mothers. They described their identity and behavior more negatively and had greater general maladjustment and neurotic symptoms. Physically abusive mothers had lower scores on self-worth in family relationships. When measured prospectively, low self-esteem appears to be a risk factor for child neglect, but is not a strong predictor for physical abuse. Implications for prevention programs are discussed. PMID- 8199905 TI - The association of physical and sexual abuse with HIV risk behaviors in adolescence and young adulthood: implications for public health. AB - This paper explores the relationship between changes in HIV risk behaviors and physical and sexual abuse. A stratified random sampling procedure selected 602 youths from a sample of 2,787 patients seen consecutively at public health clinics in 10 cities. Face-to-face structured interviews conducted since 1984-85 provide a history of change in risk behavior from adolescence to young adulthood. Univariate and bivariate analyses assessed differences in demographic and number and type of risk behaviors between those experiencing single or multiple types of abuse and those with no abuse history at all. The results show that a history of physical abuse, sexual abuse, or rape is related to engaging in a variety of HIV risk behaviors and to a continuation or increase in the total number of these behaviors between adolescence and young adulthood. This information might help practitioners to both prevent initial involvement in HIV risk behaviors and to prevent continuation of behaviors as youths move into young adulthood. PMID- 8199906 TI - Parenting behavior rating scales: preliminary validation with intrusive, abusive mothers. AB - This study provided preliminary evidence of the reliability and validity of a set of scales fro rating the parenting behaviors of physically abusive mothers. Thirty-two male and 32 female undergraduates viewed a video-tape of either an abusive or matched control mother interacting with her son. Two tapes of abusive mothers, representative of the Intrusive mother type, and two matched control tapes were used. Subjects rated the mother's behavior on rating scales matching an observational coding system developed by Oldershaw, Walters, and Hall (1989). Mean ratings of between six to eight raters displayed sufficiently high reliability. As expected, ratings correlated with behavior frequency data. Observers' ratings discriminated between abusive mothers and nonabusive controls, providing evidence of construct validity of the scales. The potential utility of a rating scale instrument for the clinical assessment of parenting behaviors is discussed. PMID- 8199907 TI - Parenting stress and social support of mothers who physically abuse their children in Hong Kong. AB - Thirty-seven identified abusive mothers were matched on demographic and socioeconomic parameters with a known nonabusive comparison sample in order to examine the role of parenting stress and maternal social support. The mothers were assessed using a personal (demographic) questionnaire, the Parenting Stress Index (PSI), and the Maternal Support Index (MSSI). Demographic data showed that the two groups were comparable on all variables except abusive mothers had significantly more children (p = .01). Abusive mothers showed significantly more stress on total PSI scores (p = .005), as well as in all three of the subjects: Child Domain (p = .007) Parent Domain (p = .02), and Life Stress (p = .016). Abusive mothers scored lower in all seven items on the MSSI. The difference was significant on the MSSI as a whole (p = .007) and on four subsets: number of people to count on in time of need (p = .02), perceived neighborhood support (p = .04), satisfaction with spousal relationship (p = .01), and degree of community involvement (p = .03). The greatest percentage (74.32%) of correct predictions of child abuse was achieved by combining the number of children, the Life Stress Scale and the MSSI. Implications for future research are discussed. PMID- 8199908 TI - Survey of home visiting programs for abused and neglected children and their families. AB - This study reports on home visitation programs that provide services for abused and neglected children and their families. Data were collected as part of a national survey of home visiting programs. Of the 1,904 programs participating in the survey, 224 had as their primary focus services for children who were abused or neglected. For this group, data are presented on program characteristics, characteristics of home visits, credentials of home visitors, and program documentation procedures. The survey data showed that over 70% of the 224 programs identified social service as their organization affiliation which, in contrast to other providers, offered a broad range of services for the abused or neglected children and their families. The most frequently identified purpose for providing services was the social and emotional development of the child. Parenting skills and parent coping were considered the most important services. Stress management was considered more important by respondents of programs for maltreating families than by those providing services to nonmaltreating families. Approximately half the respondents reported that they required a bachelor's or master's degree for employment. Results are discussed in relation to research and practice implications. PMID- 8199909 TI - Maternal Grave's disease and child abuse. PMID- 8199910 TI - On sensitivity and ethical issues in child witness research. PMID- 8199911 TI - Ethical issues in child witness research. PMID- 8199912 TI - Links between types of maltreatment and demographic characteristics of children. PMID- 8199914 TI - The importance of colostrum to the health of the neonatal calf. AB - Colostrum feeding is the means by which newborn calves acquire passive immunity to infectious agents. The ability of the newborn calf to absorb colostral antibodies is limited to the first few hours of life. In most cases, natural suckling from the dam is the best method for beef-breed calves to obtain optimum passive immune protection, but in some cases intervention and hand feeding are indicated. The details of when and how to intervene in the passive transfer process are discussed. PMID- 8199915 TI - Environmental factors and calving management practices that affect neonatal mortality in the beef calf. AB - This article reviews the relationship of environmental and calving management factors and the occurrence of neonatal mortality. The importance of these factors, considered individually or in combinations, has been the subject of a limited number of scientific investigations. As a consequence, some recommendations are based on clinical impression and reasoning rather than the results of carefully controlled field studies. Significant costs are incurred by cow/calf operators in the implementation of many of these ideas. Hopefully, they are all appropriate and useful, but more research should be conducted in this area. There is a need to learn more about environmental causes of neonatal mortality, including individual effects, the effect of various combinations of these factors, and the relative magnitude of the effect of both individual factors and various combinations of them. PMID- 8199913 TI - In utero infections responsible for abortion, stillbirth, and birth of weak calves in beef cows. AB - A multitude of in utero infections may cause abortion, stillbirths, or the birth of weak calves (see Table 1). Because the diagnostic success for determining the cause of abortions may be low (25%-40%), it is important that more knowledge about the causes and differential diagnoses is gained, and proper samples are collected and submitted. Use of an abortion diagnosis kit enables multiple samples to be analyzed and increases the likelihood of making a diagnosis. The immune response is suppressed during pregnancy. In part, this can be controlled by proper nutrition and appropriately timed vaccination programs. PMID- 8199916 TI - Physiologic mechanisms of adaptation in the fetal calf at birth. AB - At the moment the umbilicus separates from the fetus during the birthing process, several physiologic functions formerly supported by the dam must become operational in the neonate to ensure survival of the calf. These functions include the ability to maintain adequate oxygen saturation of blood, to regulate acid-base balance, to engage endogenous metabolic pathways for energy production, and to preserve body temperature within critical limits. This article reviews cardiopulmonary function, acid-base balance, and energy metabolism in the fetus and neonate. PMID- 8199917 TI - The incidence, causes, and financial impact of perinatal mortality in North American beef herds. AB - This article contains a brief overview of the magnitude and causes of perinatal calf mortality (PCM). A PATH model chart of the risk factors of PCM is presented as a foundation for preparation of herd-management programs to prevent PCM, for herd investigations to control excessive PCM, or to plan seminars for livestock producers on control of PCM. The financial impact of PCM is explored through discussions of expenses associated with PCM, management decisions after calf deaths, and a comparison of the financial losses of PCM with losses incurred through pregnancy failure. PMID- 8199918 TI - Investigating perinatal calf mortality in beef herds. AB - This article summarizes the information presented in this issue to identify the reasons for a perinatal calf mortality (PCM) problem through a risk-factor evaluation approach. The benefits of necropsies in PCM investigations are discussed, and the gross lesions of the major causes of PCM are described. The use of 2 x 2 tables to calculate odds ratios and the Chi-square method to test the validity of the odds ratios are presented as methods to determine suspected risk factors. The article concludes with a discussion of the management plan used to solve a PCM problem. PMID- 8199919 TI - Immunization of the beef cow and its influence on fetal and neonatal calf health. AB - Specific vaccine recommendations should be made by you, the veterinarian familiar with the operation, the type of cattle handled, and the disease problems cattle typically experience. There are few cookbook solutions. Fine turning the program by including or excluding certain vaccines requires working to identify the specific disease entities present in an operation. This requires good records, complete postmortem examinations, and a good diagnostic support system. Effective management to optimize the immunocompetence of the cow and the timing of administration of the vaccine is as important as selecting the correct antigens and type of vaccines to be used. PMID- 8199920 TI - Weakness in the newborn calf. AB - The peak time period for the average beef producer to experience the majority of calf losses has consistently been from the time of birth through the first seven days of life. Weakness is a principal clinical sign of diseases or conditions responsible for mortality including birth trauma, prematurity or dysmaturity, congenital malformations, metabolic defects, intrauterine infection, anoxia or hypoxia, hypothermia, starvation, extremes in birth weight, and post-natal infection. This article discusses anoxia/hypoxia and septicemia in greater detail because of their involvement as a common cause of weakness in the newborn calf. PMID- 8199921 TI - Congenital defects as a cause of perinatal mortality of beef calves. AB - Congenital anomalies occur at low levels in beef cattle. Usually, severe defects result in abortion of the calf or return to service. In cases that do reach term, however, some die while others may survive with or without assistance from the manager. Regardless of whether the calf survives, the fact that abnormal development occurred raises questions as to etiology of the defect(s) and its impact on the herd. By defining the defect and using a logical method of assessing the cause, one can assess the impact of that defect on future herd production. PMID- 8199922 TI - Dystocia-related risk factors. AB - Dystocia is one of the leading causes of calf mortality between birth and weaning in beef cattle. An understanding of the effects of parturition and dystocia on perinatal calf viability is paramount for the development of breeding and calving programs that will minimize calf losses. This article discusses the factors affecting birth weight and replacement heifer development and redefines dystocia as any birth that reduces calf viability, causes maternal injury, or reduces maternal reproduction. PMID- 8199923 TI - Cold thermoregulation in the newborn calf. AB - During the fetal to neonatal transition, the newborn calf encounters severe thermolysis due to an abrupt change in thermal environment that is compounded by evaporation of fetal fluids and severe weather conditions. Maintenance of homeothermy during the neonatal period necessitates an acute and sustained thermogenic response by the newborn calf. It is now widely accepted that this thermogenic response is derived from both shivering thermogenesis in muscle tissue and nonshivering thermogenesis in brown adipose tissue (BAT). It is critical that newborn calves possess functional BAT during the neonatal period. This article focuses on the pre- and postnatal factors that influence nonshivering thermogenesis of BAT in the neonatal calf. PMID- 8199924 TI - Gerontologic home care: a prescription for distance continuing education. AB - Visiting nurses are increasingly challenged by the health care delivery system to provide sophisticated technological care to a growing number of patients in their homes. Much of this care is devoted to the care of the older adult. Few nurses currently in practice have received formal preparation in gerontology; thus, a knowledge deficit exits. Recognizing the challenge of teaching visiting nurses to develop individual interests in the scientific and technologic aspects of gerontologic nursing, the Visiting Nurse Association of Cleveland designed and proposed a comprehensive project to teach gerontologic nursing using the American Nurses Association Standards of Gerontologic Nursing Practice (American Nurses Association, 1987) through discovery learning and distance education via computer and other educational interventions. Community health nursing offers a unique approach to linking practice to education and research and provides organizational and educational alternatives to traditional continuing education. PMID- 8199925 TI - Point-of-care technology: the 'window' into the integrated clinical database, Part 8. PMID- 8199926 TI - Confidentiality. PMID- 8199927 TI - A comparative assessment of interactive video instruction. PMID- 8199928 TI - Implementing a local area network for nursing in a large teaching hospital. AB - The authors describe the assessment, planning, implementation, and benefits of a local area network (LAN) for the nursing service of a 504-bed urban teaching hospital. The major goals of the network were to increase the efficiency and effectiveness of the nursing administrative areas and improve communication systems. A network of more than 90 workstations, spanning 12 buildings, was installed. The network provides access to multiple programs that support clinical, managerial, and research activities. Gateways provide access to the hospital's two mainframe computers. Network benefits identified by nursing management include: improved communication and access to information; increased accuracy, efficiency and timeliness of data; and improved computer literacy. PMID- 8199929 TI - A meta-analysis of computer-based instruction in nursing education. AB - Although dozens of studies regarding computer-based instruction (CBI) in nursing education have been conducted over the last 25 years, little has been done to summarize these studies quantitatively. In the current study, the authors used Glass's techniques of meta-analysis (Glass, McGaw, & Smith, 1981) to integrate statistically findings from 29 comparative studies concerning CBI. A clear majority of these studies favored CBI over conventional methods of instruction. The overall achievement effect size for 26 studies that quantified outcomes was 0.45, a medium-sized effect. Two study feature variables--type of CBI and required versus elective course--related to effect size. Interactive video applications of CBI produced larger effects than tutorial, computer-managed, and simulation applications, and CBI implementations in elective courses showed larger effects than implementations in required courses. Few studies reported on outcomes of retention, attitudes, and time to learn. The results demonstrate a need for more and better reported research to identify instructional qualities that lead to positive student outcomes. PMID- 8199930 TI - Epidemiology for community health nursing: an interactive computer assisted instruction program. AB - Epidemiology and its application to community health nursing is an essential concept for baccalaureate nursing students. To facilitate student learning, nursing faculty chose to use computer assisted instruction (CAI) as an adjunct teaching-learning strategy. An interdisciplinary team, including nursing content specialists and a computer programmer, produced an interactive CAI that integrated epidemiologic content, community health nursing practice, and learning theory principles. Contents of the program modules are described, and program strategies used to enhance learning are delineated. Evaluation of the program indicated students (N = 106) believed the content was clearly explained and preferred learning epidemiology through combining classroom learning with CAI rather than through textbook reading assignments. PMID- 8199931 TI - The management of spontaneous pneumothorax. PMID- 8199932 TI - Infection monitoring programs. PMID- 8199933 TI - Damage control: a plea for extended resuscitation. PMID- 8199934 TI - Correlation of trauma scoring and outcome in a Canadian trauma centre. AB - OBJECTIVE: To study the effectiveness of treatment and the outcome in trauma patients, and to correlate these with trauma scoring systems. DESIGN: A prospective study over 1 year of the probability of survival after trauma, based on TRISS methodology. A computerized database provided outcome statistics. SETTING: A regional trauma centre in a Canadian university teaching hospital serving regional and referral patients. PATIENTS: Three hundred consecutive patients treated at a single trauma unit. Two patients were excluded because of lack of physiologic data. Blunt injuries (94%) were most frequently from motor vehicle accidents (46%). INTERVENTIONS: Those appropriate to multidisciplinary trauma management in a level 1 trauma centre. MAIN OUTCOME MEASURES: Survival (Z values) and injury severity (M values) for the total group and subsets were calculated for comparison of outcomes with the Multiple Trauma Outcome Study baseline and other Canadian centres for multisystem and single-system injuries. RESULTS: The mean Injury Severity Score was 21.16 and the mean Revised Trauma Score was 6.75. There were 51 (17%) deaths--a Z value for the study group of 2.26. The M value was 0.78. Forty of the 51 single-system injuries were head injuries and accounted for 15 deaths. The Z value for multisystem injuries only was 0.54, and the M value was 0.77. CONCLUSIONS: The TRISS method for analysing blunt trauma is comparable to other trauma scoring systems. The correlation of outcome analysis with other scoring systems is affected by exclusion rates, pre referral resuscitation and single- versus multiple-injury mix of cases. PMID- 8199935 TI - Endoscopic carpal tunnel release. AB - OBJECTIVE: To assess the efficacy and safety of a new technique for carpal tunnel release. DESIGN: A single-group prospective cohort study. SETTING: A referral based hand-surgery university practice. PATIENTS: Ninety-five consecutive adults; 1 patient was excluded (35 men, 59 women). They underwent 108 surgical procedures. No patients were lost to follow-up. INTERVENTIONS: Endoscopic carpal tunnel release. Outpatient surgery with neuroleptic anesthesia. Two-portal Chow technique of release. MAIN OUTCOME MEASURES: Symptom relief, return to work, medication use and complication rate. RESULTS: The average preoperative duration of symptoms was 3.9 years. Nerve conduction studies were positive in 101 of the 108 hands. Only two patients required open release. Only eight patients complained of intraoperative pain. Six patients failed to obtain relief of symptoms; two of them required secondary open release owing to persistent symptoms. Of the 61 patients who were employed, 52 returned to their previous jobs without restriction. The mean time for return to work was 36.4 days for patients who were Workers' Compensation Board cases and 19.5 days for patients who were not (p < 0.01). Men returned to work in 17.7 days and women in 24.7 days (p < 0.05). Complications occurred in four patients (3.8%). No nerve injury, vascular injury or reflex sympathetic dystrophy was noted. Patients who had undergone previous contralateral open release noted less pain and earlier return to work after endoscopic carpal tunnel release. CONCLUSIONS: Endoscopic carpal tunnel release was effective in relieving symptoms and had a low complication rate. The technique was associated with early return to work and minimal palmar pain. PMID- 8199936 TI - Spontaneous primary and secondary pneumothorax: a 10-year study of management alternatives. AB - OBJECTIVE: To study the outcome of conservative and surgical management of spontaneous pneumothorax. DESIGN: Retrospective study between January 1980 and December 1990, with a mean follow-up of 6.5 years. SETTING: A tertiary-care university hospital with a referral thoracic surgical unit. PATIENTS: All patients seen in the study period with spontaneous pneumothorax. Those with traumatic, iatrogenic or ventilator-associated pneumothoraces were excluded. There were 366 consecutive patients who had 508 episodes of spontaneous pneumothorax. Two hundred and thirty-nine patients had primary spontaneous pneumothorax (group 1); 127 had secondary spontaneous pneumothorax (group 2). INTERVENTIONS: Tube thoracostomy, apical resection with either pleurectomy or pleural abrasion. MAIN OUTCOME MEASURES: Recurrence and outcome after surgical management relative to recurrence, complications, operative technique and mean hospital stay were evaluated by clinical review and questionnaire by an independent observer. RESULTS: No significant differences were noted between the two groups with respect to the incidence of recurrent spontaneous pneumothorax after the first or second episode, and no significant differences were noted between the two operative techniques with respect to recurrence, complications, operative technique or death rate. However the mean hospital stay was doubled for group 2 patients (9.9 versus 4.3 days). CONCLUSIONS: Conservative treatment, including tube thoracostomy, was effective for primary and secondary spontaneous pneumothorax. Open surgery was effective in preventing recurrence in 95% of cases in both groups. PMID- 8199937 TI - Infected tibial nonunion. AB - OBJECTIVE: To compare three methods of surgical treatment for infected nonunion of tibial fractures. DESIGN: Chart review. SETTING: Two teaching hospitals of Shiraz University Medical School in Iran. PATIENTS: Fifty-eight patients with infected nonunion of tibial fractures treated between 1976 and 1989. All patients had received antibiotic therapy before treatment for nonunion. INTERVENTIONS: Bone grafting with cast immobilization (group 1), bone grafting with insertion of compression plates (group 2) and bone grafting with intramedullary rod fixation (group 3). MAIN OUTCOME MEASURES: A clinical scoring system based on functional ability, range of knee and ankle motion, shortening, infection and pain. RESULTS: After the first operation union was achieved in 75% of group 1 patients, 84% of group 2 and 100% of group 3; 41% of patients had excellent or good results and 47% had fair or poor results. Twelve percent of patients had nonunion (failure). Union in fractures treated with intramedullary rod fixation (group 3) occurred faster, and patients in this group had a higher number of good or excellent results than those in the other groups. Treatment without fixation (group 1) resulted in fair or poor results in over 50% of cases. CONCLUSION: In terms of union and function, the best surgical treatment for infected nonunion of tibial fractures in this series was bone grafting and intramedullary rod fixation, after adequate debridement and antibiotic therapy. PMID- 8199938 TI - Changing patterns of scaphoid fractures in adolescents. AB - OBJECTIVE: To determine if the presentation of scaphoid fractures in children has changed. DESIGN: Case study with a minimum follow-up of 1 year. SETTING: Outpatient orthopedic clinic in an urban pediatric hospital. PATIENTS: Twenty-one adolescents (mean age 13.9 years) with scaphoid fractures and an open distal radial growth plate. Fracture healing was assessed at 2-week intervals until union was achieved. INTERVENTIONS: Immobilization in a short-arm thumb spica cast. MAIN OUTCOME MEASURES: Fracture union as defined by the absence of pain and obliteration of the fracture line. Active and passive range of motion of wrist as measured with a goniometer. RESULTS: Only 2 of the 21 patients had avulsed fractures. Twelve fractures were located in the middle one-third of the scaphoid. All fractures healed, but two fractures were in a dorsiflexed position. All patients had full, painless range of wrist motion. No arthrosis was present. CONCLUSIONS: The presentation of scaphoid fractures in adolescents has changed over the years and now resembles the adult pattern. Malunited scaphoid fractures may be seen. Displaced fractures should be reduced. PMID- 8199940 TI - Compression forces generated by the Huene alignment guide alone. AB - To enhance the fixation of scaphoid fractures by providing precise alignment and compression at the fracture site, the Huene alignment guide has been used in conjunction with bone screws. In an effort to predict the compressive force generated by the Huene guide alone, these forces were measured with a calibrated, strain-gauge, instrumented device. Three orthopedic surgeons each tested the guide 10 times on one cadaver scaphoid bone specimen. The magnitude of the compressive forces generated ranged from 9.0 to 67.0 N (mean 36.0 +/- 15.0 N). Comparisons of the force measurements among the individuals revealed no significant differences. This wide range of measurements could be attributed to the variability of the ratchet mechanism on the device. Because the Huene alignment guide is used to generate transcaphoid compressive forces, these results demonstrate that it does not yield consistent compression. PMID- 8199939 TI - Wound infection in total joint arthroplasty: effect of extended wound surveillance on wound infection rates. AB - OBJECTIVE: To determine the effects of a wound monitoring program on infection rates after total joint arthroplasty. DESIGN: Case series, comparing postoperative wound infection rates before and after hospital discharge. SETTING: A university-affiliated tertiary-care hospital. PATIENTS: A group of 865 patients who underwent primary or revision total hip or knee arthroplasty between September 1989 and September 1991 followed by in-hospital and post-discharge wound monitoring was compared with a baseline group of 204 patients who had undergone an arthroplasty procedure and in-hospital wound monitoring between March and September 1988; only 38 of these patients were selected for post discharge monitoring. INTERVENTIONS: In the study group, wounds were monitored every 48 to 72 hours to the time of patient discharge and at 30 days post discharge. Monthly reports of surgeon-specific and overall infection rates were sent to each surgeon during both baseline and study periods. MAIN OUTCOME MEASURES: Presence or absence of surgical wound infection. RESULTS: The initial overall wound infection rate was 9.9%. This decreased to 3.8% in the study group, after the wound monitoring program had been in place for at least 18 months. Post discharge monitoring accounted for the majority of wound infections diagnosed. CONCLUSIONS: A wound monitoring program may be an important tool in lowering wound infection rates associated with total joint arthroplasty. Post-discharge monitoring is important in determining true wound infection rates. PMID- 8199941 TI - Dislocation of posteriorly stabilized total knee arthroplasties. AB - Two cases of dislocation of an Insall-Burnstein II knee are reported. They occurred when a rotational force was applied to the loaded knee positioned in extreme flexion. Both dislocations were reduced closed and were found to be stable in the reduced position. The patients did well, and revision surgery was not required. No case of dislocation of this particular posterior stabilized total knee system has been reported previously. PMID- 8199942 TI - The lateral calcaneal flap for sensate heel reconstruction revisited. AB - Defects of the heel can be difficult to treat because they require a thin, sensate, soft-tissue cover. The lateral calcaneal flap can provide this type of reconstruction in selected patients. A 27-year-old man had a painful defect in a grafted heel that prevented him from working. A satisfactory painless heel was provided by resurfacing the area with a lateral calcaneal flap. The donor defect was minimized by interfascicular dissection of the sural nerve. PMID- 8199943 TI - Progression toward malignancy of hamartomas in a patient with Peutz-Jeghers syndrome: case report and literature review. AB - Peutz-Jeghers syndrome, inherited in an autosomal dominant fashion, is characterized by hamartomatous polyps of the gastrointestinal tract and by mucocutaneous pigmentation. The frequency of gastrointestinal malignant disease in this syndrome is estimated to be 2% to 3%. The authors review reports associating Peutz-Jeghers syndrome with malignant disease and present a patient who had advanced jejunal adenocarcinoma in association with Peutz-Jeghers syndrome. It has not been determined with certainty whether the malignant lesions arise from hamartomas, from associated adenomatous polyps or from the normal mucosa. Histologic examination of the excised specimen from the patient reported in this paper showed areas typical of a hamartoma as well as areas of hyperplasia, adenoma with mild to severe dysplasia and carcinoma in situ all in the same polyp. These findings suggest that the hamartomatous polyps found in Peutz-Jeghers syndrome have the potential to undergo malignant transformation. PMID- 8199944 TI - Abbreviated laparotomy for damage control: a case report. AB - During the initial operation on victims of multisystem trauma, life-threatening hypothermia, metabolic acidosis and coagulopathy occasionally develop. Without the immediate control of active bleeding and correction of these abnormalities, the intraoperative death rate is high. A patient with severe abdominal trauma was successfully managed with staged laparotomies. The patient's initial surgery was abbreviated to allow the aggressive correction of hypothermia and coagulopathy before definitive reconstruction of bowel injuries. Abbreviated laparotomy for damage control should be a part of the surgical armamentarium in the management of severe abdominal trauma. PMID- 8199945 TI - Lost gallstones during laparoscopic cholecystectomy: are they really benign? AB - The long-term effect of stones spilled into the peritoneal cavity during laparoscopic cholecystectomy is unknown. The course of a 58-year-old man who had recurrent right subphrenic abscesses and a right empyema secondary to spilled gallstones during laparoscopic cholecystectomy is described. The authors outline techniques for minimizing the spillage of stones during laparoscopic cholecystectomy: the application of hemoclips, endoloops and sutures, and placement of the necrotic, friable gallbladder in an endoscopic bag immediately upon completion of the dissection, before extraction of the gallbladder. They conclude that spillage of stones during laparoscopic cholecystectomy may lead to serious infection and should be recorded in the operative notes so that stones may be suspected when a patient presents with abdominal infection after laparoscopic cholecystectomy. PMID- 8199946 TI - Tumour implantation at umbilicus after laparoscopic cholecystectomy for unsuspected gallbladder carcinoma. AB - Seeding of tumour cells at the umbilical port during laparoscopic surgery for staging malignant disease has been reported. In this paper a 69-year-old woman is described who had umbilical metastasis after laparoscopic cholecystectomy for unsuspected gallbladder cancer. The experience of this case and that of other reports suggests that when laparoscopic techniques are used for the resection of tumours, the excised specimen should be enclosed in a nonporous bag for removal through the abdominal wall. PMID- 8199947 TI - Invasive Clostridium septicum infection in association with colorectal carcinoma. AB - The association between invasive Clostridium septicum infection and colorectal carcinoma is examined by the presentation of three cases and a review of the literature. In the first two cases the patients presented with nontraumatic metastatic clostridial gas gangrene. In the third case a patient with chemotherapy-induced myelosuppression from concomitant multiple myeloma had a necrotizing transmural infection of the right colon. The apparent portal of entry of Clostridium septicum was an occult carcinoma of the ascending colon. The increasing evidence for a strong link between this organism and some cases of neutropenic enterocolitis is reviewed. PMID- 8199948 TI - Support for future physicians. PMID- 8199949 TI - Support for future physicians. PMID- 8199950 TI - Fatal anaphylactic reactions to food in children. PMID- 8199951 TI - Pain relief during childbirth. PMID- 8199952 TI - Pain relief during childbirth. PMID- 8199954 TI - Patient satisfaction: the power of an untapped resource. PMID- 8199953 TI - Medicine and health care: a marriage of necessity. PMID- 8199955 TI - [Risk of pregnancy complications associated with residency]. AB - OBJECTIVE: To determine, through a review of published articles, whether a higher prevalence of pregnancy complications is associated with residency in medicine. DATA SOURCES: Articles published between January 1980 and December 1992 found through a MEDLINE search using the MeSH terms "pregnancy complications" and "internship and residency" and through a review of the bibliographies of articles found. STUDY SELECTION: Of the 17 articles found, 6 contained data on the prevalence of pregnancy complications in residents. DATA EXTRACTION: The methodologic quality of the studies was evaluated systematically with the use of a grid. Data on the prevalence of the six most common pregnancy complications were retained. DATA SYNTHESIS: Four of the six articles had methodologic weaknesses (missing or inappropriate control groups, poorly controlled historical bias). The best study showed a higher prevalence of premature labour, pre eclampsia and voluntary abortion in the residents than in the control subjects. CONCLUSIONS: It is difficult to draw definitive conclusions from a single study that met the criteria for methodologic quality. More and better-controlled studies involving larger numbers of subjects are needed. PMID- 8199956 TI - Evidence-based care: 4. Improving performance: how can we improve the way we manage this problem? Evidence-Based Care Resource Group. AB - The first step in improving physician performance when there are gaps between what physicians are doing and what they should be doing is to diagnosis the causes of suboptimal care. This "diagnosis" then guides the selection of the most efficient and effective strategies to improve performance. Some behaviours may be easy to change, but the factors that cause suboptimal care often present formidable barriers. Physicians are most likely to improve their performance in these situations if they use a combination of strategies that predispose them to provide improved care, enable them to do so and reinforce these changes in behaviour. Feedback on progress is always important, to ensure that physicians adapt and to provide personal satisfaction and positive reinforcement when performance does improve. Individualized strategies are also important: there are differences in physicians' learning experiences, practice environments and needs. Therefore, each physician must tailor his or her methods for learning and improving performance to his or her individual clinical practice. PMID- 8199957 TI - Questionable prescribing for elderly patients in Quebec. AB - OBJECTIVE: To estimate the prevalence of questionable and rational high-risk prescribing among elderly people of the three drug groups most commonly implicated in drug-related illness: cardiovascular drugs, psychotropic drugs and nonsteroidal anti-inflammatory drugs (NSAIDs). DESIGN: Retrospective prevalence study; all prescription and billing records for the period Jan. 1 to Dec. 31, 1990, for the study sample were retrieved from the relevant provincial databases of the Regie de l'assurance-maladie du Quebec. SETTING: Quebec. PARTICIPANTS: Regionally stratified random sample of 63,268 elderly medicare registrants who made at least one visit to physician in 1990 and were not living in a health care institution for the entire year. MAIN OUTCOME MEASURE: Prescription information was examined for three types of high-risk prescribing: rational and questionable drug combinations, excessive treatment duration and drugs relatively contraindicated for use in elderly people. RESULTS: Overall, 52.6% of the patients experienced one or more events of high-risk prescribing, and 45.6% experienced at least one that was questionable. High-risk prescribing was most prevalent for psychotropic drugs, and questionable prescribing was more frequent than rational prescribing in this drug group. An estimated 30.8% of the total elderly population in Quebec received benzodiazepines for more than 30 consecutive days, 12.9% received a long-acting benzodiazepine, and 13.0% received a questionable high-risk psychotropic drug combination. The prevalence of high risk prescribing was higher among the women than among the men and increased with age until 75 to 84 years. There were significant unexplained differences between regions in the regional prevalence of high-risk prescribing, particularly of psychotropic drugs. CONCLUSION: The prevalence of questionable high-risk prescribing, especially of psychotropic drugs, is substantial among elderly people. This may be a potentially important and avoidable risk factor for drug related illness in elderly people. PMID- 8199958 TI - How was your hospital stay? Patients' reports about their care in Canadian hospitals. AB - OBJECTIVE: To survey adult medical and surgical patients about their concerns and satisfaction with their care in Canadian hospitals. DESIGN: Cross-sectional telephone survey undertaken from June 1991 to May 1992 with a standardized questionnaire. SETTING: Stratified random sample of public acute care hospitals in six provinces; 57 (79%) of the 72 hospitals approached agreed to participate. PATIENTS: Each participating hospital provided the study team with the names of 150 adult medical and surgical patients discharged home in consecutive order. A total of 4599 patients agreed to be interviewed (69% of eligible patients and 89% of patients contacted). MAIN OUTCOME MEASURES: Satisfaction with (a) provider patient communication (including information given), (b) provider's respect for patient's preferences, (c) attentiveness to patient's physical care needs, (d) education of patient regarding medication and tests, (e) quality of relationship between patient and physician in charge, (f) education of and communication with patient's family regarding care, (g) pain management and (h) hospital discharge planning. RESULTS: Most (61%) of the patients surveyed reported problems with 5 or fewer of the 39 specific care processes asked about in the study. Forty-one percent of the patients reported that they had not been told about the daily hospital routines. About 20% of the patients receiving medications reported that they had not been told about important side effects in a way they could understand; 20% of the patients who underwent tests reported similar problems with communication of the test results. Thirty-six percent of those having tests had not been told how much pain to expect. In discharge planning, the patients complained that they had not been told what danger signals to watch for at home (reported by 39%), when they could resume normal activities (by 32%) and what activities they could or could not do at home (by 29%). Over 90% of the patients reported that they had had a relationship of confidence and trust with their physician and that they had been involved in decision making as much as they wanted to be. Fifteen percent of the patients whose admissions had been scheduled felt that they should have been admitted sooner. CONCLUSION: The self-reported patient data from this survey suggest that hospital routines, medications, tests, pain management and discharge planning are areas of communication to target in future quality-improvement efforts in Canadian hospitals. PMID- 8199959 TI - Guidelines for control of meningococcal disease. Laboratory Centre for Disease Control. Canadian Consensus Conference on Meningococcal Disease. PMID- 8199960 TI - US health care reforms may create heavy demand for Canada's primary care MDs. PMID- 8199961 TI - Growth in number of advertisements indicates increased US interest in Canadian MDs. PMID- 8199962 TI - Did Alberta attempt to cut health care costs too quickly? PMID- 8199963 TI - Interpretation for Inuit patients essential element of health care in eastern Arctic. PMID- 8199964 TI - Keep facts from patients at your peril, Ontario court warns doctors. PMID- 8199965 TI - The RCAMC and the beaches of Normandy. PMID- 8199966 TI - Ontario's Institute for Clinical Evaluative Sciences walks tightrope between MDs, government. PMID- 8199967 TI - Saskatchewan moves to cut tonsillectomy rate. PMID- 8199968 TI - The patient-physician relationship and the sexual abuse of patients. AB - The CMA's policy on the patient-physician relationship and the sexual abuse of patients follows a review of policies and initiatives of its provincial and territorial divisions and other professional associations. The CMA's approach to this policy has been to consider the overall patient-physician relationship in order to understand factors associated with functional and dysfunctional relationships, including those involving sexual abuse. In addition to defining abuse of patients by physicians in general and sexual abuse in particular this document gives guidelines on such issues as sexual or romantic relationships with current or former patients and provides educational and preventive strategies. PMID- 8199969 TI - A gentle revolution in community care is under way in Britain. PMID- 8199970 TI - Clinical-trial registration. PMID- 8199971 TI - "Abuse" in medical school? PMID- 8199972 TI - Canadian physicians in wartime. PMID- 8199973 TI - Canadian physicians in wartime. PMID- 8199974 TI - Canadian physicians in wartime. PMID- 8199975 TI - Evidence-based care: 5. Lifelong learning: how can we learn to be more effective? Evidence-Based Care Resource Group. AB - The authors have developed by trial and error some guidelines for teaching and learning the skills needed to provide evidence-based care. Educational activities should be applied, participatory, self-directed, practice-based and practical, and they should focus on high-priority problems. Efficiency should be emphasized, and expectations of how much any clinician can accomplish should be reasonable. PMID- 8199976 TI - Physicians in health care management: 6. Physician *bytes* computer. AB - Revolutionary advancements in information technology are improving access to medical information, operational efficiency and clinical effectiveness. Health care facilities and agencies are planning to acquire information systems that will affect clinical and administrative functions. Federal and provincial agencies are beginning to define and collect diverse health care data and integrate them in a national database. As the demand for and access to information grows physicians will be key providers and users. They will have increasing access to critical patient data through clinical information systems; however, their practice patterns, clinical outcomes and resource utilization will also be subject to increasing scrutiny. To ensure appropriate use of technology and information systems, careful planning, selection, implementation and management will be needed. Physicians will require training to use the information and systems effectively. They must also recognize the increasing importance of such systems in delivering and managing health care; they must play a pivotal role in resolving management, information and systems issues and in promoting sound information and management strategies; and they must encourage research and education in medical informatics. PMID- 8199977 TI - Reliability of the Guide to Pregnancy Risk Grading of the Ontario Antenatal Record in assessing obstetric risk. AB - OBJECTIVE: To assess the reliability of the Guide to Pregnancy Risk Grading of the Ontario Antenatal Record through evaluation of inter- and intra-observer agreement on the grading of obstetric risk. DESIGN: Retrospective chart review. SETTING: Urban community teaching hospital in Hamilton, Ont. PATIENTS: Obstetric charts of 77 women were randomly selected from those of all women who delivered at the hospital or were transferred before delivery to the regional perinatal centre between Apr. 1, 1987, and Mar. 31, 1988. Six family physicians and two obstetricians participated as chart reviewers. MAIN OUTCOME MEASURES: Agreement beyond chance (kappa [kappa] statistic) between (a) different reviewers, (b) the same reviewer at different times and (c) the majority of reviewers (majority risk grade) and the antenatal record. MAIN RESULTS: The kappa value for interobserver agreement ranged from 0.48 (95% confidence interval [CI] 0.34 to 0.62) to 0.51 (95% CI 0.36 to 0.66). For intraobserver agreement it was 0.69 (95% CI 0.37 to 1.0). Agreement between the majority risk grade and the risk grade last recorded in the antenatal record had a kappa value of 0.58 (95% CI 0.54 to 0.61). CONCLUSION: The guide possesses only modest reliability. Efforts should be made to make descriptions of risk factors more explicit and to improve the training of health care providers in the use of the guide in order to prevent errors in pregnancy risk assessment and resulting inappropriate patient care and misdirection of health care resources. PMID- 8199978 TI - [Severe rhabdomyolysis in a patient receiving lovastatin, danazol, and doxycycline]. AB - Combinations of lovastatin and other drugs have been reported to cause rhabdomyolysis and myoglobinuria. The authors report such a case in a 72-year-old man who had been receiving atenolol, acetylsalicylic acid (ASA), dipyridamole, lovastatin, danazol, prednisone and doxycycline. The ASA, lovastatin and danazol were discontinued. The symptoms resolved, and laboratory test results were normal within 2 weeks. Lovastatin was strongly suspected; danazol was the most likely potentiator by diminishing the metabolism of lovastatin and its metabolites in the liver or by having a direct toxic effect on the muscles. PMID- 8199979 TI - Forging a new subspecialty: general internal medicine. PMID- 8199980 TI - Foreign medical-education market represents potential cash infusion for Canadian schools. PMID- 8199981 TI - Physicians and the media: lessons from the school of hard knocks. PMID- 8199982 TI - Canada's new Medical Hall of Fame pays homage to medicine's giants. PMID- 8199983 TI - Childhood cancer survivors. Past, present, and future. PMID- 8199984 TI - Scintigraphic assessment of salivary function and excretion response in radiation induced injury of the major salivary glands. AB - BACKGROUND: Both loss of the secretory function and impairment of the excretion may play a role in radiation-induced injury of the major salivary glands after radiotherapy for head and neck malignancies. Therefore, quantitative 99mTc pertechnetate (99mTc) salivary scintigraphy to assess trapping, secretion, and excretion, was used to analyze irradiation-induced changes in relation to the radiation dose and the time interval after radiotherapy. PATIENTS AND METHODS: Salivary scintigraphy was performed on 25 patients who had been irradiated to the neck and head for various malignancies with irradiation of the major salivary glands and in 6 nonirradiated patients. Excretion was induced by stimulation with carbachol (Carbacholum, Pharmachemie BV, Haarlem, The Netherlands). As a parameter for salivary glandular trapping and secretion, the cumulative 99mTc pertechnetate glandular uptake in the first 12 minutes was used. Scintigraphic data were analyzed for each patient and for each individual gland at three radiation dose levels (range, 5-70 Gy), and at short (range, 2-7 months) and long (range, 10-50 months) intervals after radiotherapy. RESULTS: The excretion response to the stimulant carbachol was totally or partially disturbed in 84% of the irradiated patients. For individual glands, excretion was maintained in all glands irradiated with 25 Gy or less, in nearly half of the glands at doses of 25 45 Gy, and was almost invariably impaired at doses higher than 45 Gy, regardless of the time interval after radiotherapy. Although cumulative 99mTc glandular uptake tended to decrease at higher radiation dose levels (z = -3.059, P < 0.0022), at 45 Gy or more, cumulative 99mTc uptake was considerably higher in glands examined at a short postirradiation interval compared with glands examined after a long time interval (P = 0.0001). This tendency, seen for both parotid and submandibular glands, was not observed at doses lower than 45 Gy. CONCLUSION: These data suggest that in the first period after high dose irradiation, xerostomia is based predominantly on the failure of the gland to excrete saliva, whereas in the later period, a decreased trapping ability together with loss of secretory function play an additional role. Salivary scintigraphy using 99mTc pertechnetate is a suitable method to assess radiation-induced salivary gland injury. The test is able to detect salivary glandular dysfunction in an early phase and may be useful to predict which patients will respond symptomatically to salivary stimulants. PMID- 8199986 TI - Immunohistochemical evidence of aberrant bcl-2 protein expression in gastric epithelial dysplasia. AB - BACKGROUND: bcl-2 protein encoded by the proto-oncogene bcl-2 confers to the cell a survival advantage by inhibiting apoptosis. Its aberrant expression has been reported in lymphomas and lung carcinoma. To determine if bcl-2 plays a role in the gastric carcinogenic sequence, the authors studied bcl-2 expression in gastric epithelial dysplasia (GED) and chronic atrophic gastritis with intestinal metaplasia (CAG-IM). METHODS: Immunohistochemical staining using monoclonal bcl-2 protein antibody, clone 124, was performed on archival material. RESULTS: bcl-2 staining was seen in 13 of 16 GEDs (81%). The staining was heterogeneous, suggesting that within the dysplastic epithelium, some cellular clones may have a survival advantage. When noted, the staining in IM was located in the proliferative zone, but some positivity could also be noted higher up along the cellular escalator. Normal gastric mucosa stained in the proliferative zone. CONCLUSIONS: The authors demonstrated that bcl-2 expression is noted in GED as well as in the extended proliferative zone of CAG-IM. This suggests that prolonged cell survival due to inhibition of apoptosis is instrumental in addition to increased cellular proliferation in the altered cellular homeostasis of the gastric carcinogenic sequence. Whether bcl-2 protein aberrant expression is an independent process or inherent to immaturity of the cells produced by the increased proliferation awaits further studies. PMID- 8199985 TI - Small cell carcinoma of the esophagus. AB - BACKGROUND: Small cell carcinoma of the esophagus is regarded as having a poor prognosis with frequent systemic dissemination. METHODS: A review of the records and histologic sections of 11 patients with primary small cell carcinoma of the esophagus seen in 11 years was undertaken. They were analyzed and compared with the more common squamous cell carcinomas and adenocarcinomas. RESULTS: Small cell carcinoma of the esophagus constituted 1% of all esophageal tumors and was mainly located at the middle and lower thirds (90%) of the esophagus. Primary treatment consisted of tumor resection in five patients (46%), chemotherapy and radiotherapy in two (18%); surgical bypass in one (9%), radiotherapy after exploratory laparotomy in one (9%), intubation in one (9%), and no active intervention in one (9%). Two of the five resected tumors were Stage IIB disease, and three were Stage III disease. Five of the six patients in the non-resection group had distant metastases at presentation (45% of all patients). The median survival of patients who had chemotherapy (three of whom also had radiotherapy) was 16.7 months (range, 2.8-72 months) and was 2.2 months (range, 4 days to 9.1 months) for those with no chemotherapy. The overall median survival was 3.1 months for all patients. The prognosis was not significantly different from those with squamous cell carcinomas or adenocarcinomas. CONCLUSIONS: Small cell carcinoma of the esophagus should be regarded as a systemic disease, and multimodality treatment, including chemotherapy, should be used. Surgery may be offered in selected patients to manage local disease as part of a chemotherapy based treatment program. PMID- 8199987 TI - Chronotherapy with 5-fluorouracil and folinic acid in advanced colorectal carcinoma. Results of a chronopharmacologic phase I trial. AB - BACKGROUND: Chronotherapy with antineoplastic drugs is a rather new strategy of reducing cytotoxic side effects. Because the circadian timing of 5-fluorouracil (5-FU) was reported to result in a higher efficacy and lower toxicity, the authors conducted a chronopharmacologic Phase I trial with 5-FU and folinic acid (FA). METHODS: Eight patients with advanced colorectal cancer received 5-FU (initial dose of 500 mg/m2/day) and FA (20 mg/m2/day) as a continuous intravenous infusion over 5 consecutive days. Using a portable, ambulatory drug delivery system, 75% of the daily dose of 5-FU and FA were given from Oh00-7h00, and the remaining 25% from 7h00-24h00. Treatment courses were repeated after 28 days. Dose escalations of 250 mg/m2/day of 5-FU and 10 mg/m2/day of FA per course were performed in the absence of any toxicity greater than WHO (World Health Organization) grade 2. RESULTS: Dose-limiting toxicity WHO grade 3 was observed at a dose of 750 mg/m2/day of 5-FU and 30 mg/m2/day of FA in five, and 1000 mg/m2/day of 5-FU and 40 mg/m2/day of FA in two patients, respectively. One patient tolerated 1000 mg/m2/day of 5-FU and 40 mg/m2/day of FA, but the treatment was stopped before further dose escalation because of rapid disease progression. Mucositis was the dose-limiting toxicity in seven patients and diarrhea in two. Disease stabilization occurred in three patients and disease progression in five. Compared with conventional Phase I/II trials using a 5-day infusion regimen, the maximal tolerated dose of 5-FU and FA was slightly higher but significantly lower than in a chronotherapeutic trial that used a different, sinusoidal mode of drug application. CONCLUSION: Based on these results, the authors feel justified to caution that the circadian timing of 5-FU plus FA may not always allow the safe application of high dose levels. Future Phase I/II studies need to define whether specific drug delivery systems or schedules are necessary for chronotherapy with 5-FU and FA in patients with colorectal carcinoma. PMID- 8199988 TI - Prognostic significance of the loss of heterozygosity of Nm23-H1 and p53 genes in human colorectal carcinomas. AB - BACKGROUND: Nm23 is a gene associated with low tumor metastatic potential and has been proposed to be a metastasis suppressor gene. Nm23 is localized on chromosome 17q21.3-22, whereas the p53 suppressor gene is on 17p13. Allelic deletions of chromosome 17 have been related to the progression of colorectal carcinomas. The purpose of this study was to analyze the allelic deletions of Nm23 and p53 in colorectal carcinomas and to assess their prognostic significance in the evolution of the patients. METHODS: Allelic deletions of Nm23 and p53 genes were studied in 56 colorectal carcinomas using different restriction fragment length polymorphisms. DNA ploidy and proliferative activity of the tumors were studied by flow cytometry. Actuarial disease free and overall survival were analyzed by the Kaplan--Meier method, and the curves were compared with the log rank test. RESULTS: Thirty-eight patients were heterozygous for Nm23 gene (68%), and 9 of them (24%) exhibited a loss of heterozygosity in the tumor sample. One of the homozygous patients showed a loss of both Nm23 alleles. Allelic deletions of 17p13 were found in 63% of the 41 informative patients. All patients' tumors that had loss of heterozygosity of the Nm23-H1 locus also had allelic losses on the short arm of chromosome 17 (17p13) and in other loci on 17q. No relationship was found between localization, invasion, lymph node metastasis, or proliferative index of the tumors and the allelic deletions of the Nm23-H1 or 17p13 locus. Nm23 H1 deletions were relatively more frequent in poorly differentiated adenocarcinomas (P = 0.03). A significant association between 17p13 deletions and DNA aneuploidy was found (P = 0.016). A similar tendency was observed with Nm23 H1 deletions (P = 0.051). Loss of Nm23-H1, but not of 17p13, was significantly associated with a shorter disease free (P = 0.025) and overall (P = 0.04) patient survival. CONCLUSIONS: Allelic deletions of Nm23-H1 are significantly associated with a more aggressive behavior of colorectal carcinomas. The loss of this gene seems to be part of extensive deletions of chromosome 17, and it is also associated with DNA aneuploidy. More studies are needed to determine whether Nm23 H1 or a gene linked to this locus is the specific target of the progression of these tumors. PMID- 8199989 TI - Invasive growth patterns of hepatic hilar ductal carcinoma. A histologic analysis of 18 surgical cases. AB - BACKGROUND: Postoperative recurrence of hepatic hilar ductal carcinoma usually occurs in a localized region around the surgical margin, such as the bile duct. This study was aimed at assessing the invasive patterns of the hepatic hilar ductal carcinoma by histologically examining surgical specimens obtained by extended liver resection, especially the involvement of intrahepatic duct. METHODS: Eighteen resected specimens of hepatic hilar ductal carcinoma were histologically investigated. Multiple sections vertical to the extrahepatic and intrahepatic bile duct were made at a 5-mm interval. The extension of carcinoma was evaluated on each of three layers (mucosal, extramucosal-intramural, and extramural), and routes of the invasion were examined. RESULTS: Extramucosal extent toward the hepatic side was observed in 14 patients (77.8%) and that toward the duodenal side in 8 patients (44.4%) (P < 0.05). The distance of extramucosal tumor extent was also significantly longer (P < 0.05) in the hepatic side than in the duodenal side. Histologic tumor margin was usually identified in the extramural layer. Two patients had discontinuous extramucosal invasion. The lymphatic invasions were observed most frequently, followed by perineural invasion, and venous invasion was rare. In the extramucosal invasion of the liver, the left dominant carcinomas had extended toward the left, whereas those right dominant had extended toward the right (P < 0.05). Well differentiated differentiated tubular adenocarcinomas extended to the liver more extensively than moderately and poorly differentiated ones, but not significantly. CONCLUSIONS: The authors examined the extramucosal invasion of hepatic hilar ductal carcinoma. This invasion extended more frequently and further to the hepatic side than to the duodenal side, usually by the route of the extramural layer. PMID- 8199990 TI - Intraoperative radiation therapy adjuvant to resection in the treatment of pancreatic cancer. AB - BACKGROUND: Local recurrence is the most frequent site of failure after resection for pancreatic cancer. Tolerance, local control, and survival obtained by the association of resection and intraoperative radiation therapy (IORT) were reported. METHODS: Between June 1985 and March 1993, 90 resections for pancreatic cancer were performed at the authors' institution. For 43 patients, IORT was added to resection (Group 1), whereas the other 47 patients underwent resection alone (Group 2), because of either the unavailability of linear accelerator or the patient's refusal. In Group 1, radiation doses from 12.5 to 20 Gy, with electron beam energies between 6 and 12 MeV, were delivered. Extension of the disease was similar in the two groups of patients: mean diameter of the tumor was 3.2 cm in Group 1 and 3.4 cm in Group 2; percentage of third degree stage disease (International Union Against Cancer classification) was 65.1% in Group 1 and 57.4% in Group 2; and tumor clearance was incomplete in 39.5% of patients in Group 1 and in 34.0% in Group 2. RESULTS: Operative mortality and overall early post-operative complications were respectively 2.3% and 23.2% in Group 1 and 2.1% and 23.4% in Group 2. One-year, 2-year, and 3-year survival rates were respectively 71%, 24%, and 7% in Group 1 and 49%, 16%, and 10% in Group 2 (P was not significant). Median disease free survival was 13 months in Group 1 and 8 months in Group 2 (P was not significant). A local recurrence was detected in 27.0% of patients in Group 1 and in 56.4% of patients in Group 2 (P < 0.01). CONCLUSIONS: The results suggest a better local control in patients with pancreatic cancer undergoing adjuvant IORT. PMID- 8199991 TI - Pleomorphic (spindle/giant cell) carcinoma of the lung. A clinicopathologic correlation of 78 cases. AB - BACKGROUND: The authors undertook this study to define the clinical and histologic characteristics of spindle and giant cell carcinomas of the lung and the survival and prognostic features of these tumors. METHODS: Seventy-eight cases of pleomorphic (spindle and/or giant cell) carcinoma of the lung were studied by light microscopy and immunohistochemistry to establish clinical, gross, and histologic parameters. Follow-up information was obtained from contributing physicians and analyzed by statistical means to determine prognostically significant parameters. RESULTS: The patient population consisted of 57 men and 21 women (male to female ratio, 2.7 to 1) between the ages of 35 and 83 years (mean, 62 years). Clinically, 58 patients (80%) presented with symptoms including thoracic pain, cough, and hemoptysis, whereas 14 (18%) were asymptomatic. At the time of diagnosis, 41% of the patients had clinical Stage I lesions, 6% Stage II lesions, 39% Stage III lesions, and 12% Stage IV lesions. Histologically, foci of squamous cell carcinoma were present in 8% of the tumors, large cell carcinoma in 25%, and adenocarcinoma in 45%. The remaining 22% of neoplasms were completely spindle and/or giant cell carcinomas. Spindle and giant cell carcinomas were found together in 38% of the patients. In the 69 patients for whom follow-up information was obtained, 53 (77%) died within 7 days to 6 years after diagnosis, with a 23-month mean survival (median, 10 months) (Kaplan Meier method). There was a significant shortening of survival for patients with tumor size greater than 5 cm, clinical stage greater than 1, and lymph node involvement. The presence of nodal metastases was the most significant single prognostic factor, whereas the presence of squamous or adenocarcinomatous differentiation did not have an impact on length of survival. CONCLUSIONS: The frequency with which spindle and giant cell carcinomas are found together, their frequent association with other histologic subtypes of lung carcinoma, and the similar clinicopathologic features of these tumors suggest that they are best regarded as one type of lung cancer called pleomorphic carcinoma. PMID- 8199992 TI - All-trans retinoic acid followed by chemotherapy for salvage of refractory or relapsed acute promyelocytic leukemia. AB - BACKGROUND: All-trans retinoic acid (ATRA) is effective in the treatment of relapsed or refractory acute promyelocytic leukemia (APL), but relapse is the rule if response is unmaintained. METHODS: Seventeen patients with APL were salvaged with ATRA at a dosage of 50 mg/m2/day for 3 months or until complete remission (CR) was achieved; idarubicin (12 mg/m2/day for 4 days) was added if blast plus promyelocyte count either was or reached > or = 10 x 10(3)/microliters. After CR was achieved, patients received three courses of idarubicin (12 mg/m2 daily for 3 days) followed by three courses of mitoxantrone (5 mg/m2 daily for 3 days) and etoposide (250 mg/m2 daily for 3 days). Maintenance was with 6-mercaptopurine and methotrexate. RESULTS: A CR was achieved in 14 patients (82%), the disease was refractory in 2 patients, and one patient died during induction. Three patients underwent allogeneic bone marrow transplant during CR. After a median follow-up of 26 weeks, six patients remain in CR. Median CR duration is 40 weeks (range 8-56+). Patients treated with ATRA plus chemotherapy in first salvage, when compared to a historic control group treated with chemotherapy alone, had a significantly better CR rate (87% vs. 57%; P = 0.04) and a lower induction death rate (7% vs. 29%; P = 0.08), resulting in longer median survival (26 vs. 17 weeks; P = 0.13). Four patients developed the "retinoic acid syndrome", which was fatal in one case. Three patients developed thrombotic events. CONCLUSIONS: ATRA followed by chemotherapy is effective treatment for patients with APL who relapse after conventional therapy, and it may be superior to chemotherapy alone. PMID- 8199993 TI - Successful treatment of lentigo maligna and lentigo maligna melanoma with Mohs' micrographic surgery aided by rush permanent sections. AB - BACKGROUND: Lentigo maligna (LM) is a pigmented neoplasm on sun-exposed skin of elderly patients. LM slowly increases in size and may become lentigo maligna melanoma (LMM), a potentially fatal malignancy. Complete excision is the treatment of choice. Mohs' micrographic surgery (MMS) with frozen and permanent sections may be used for complete eradication of the lesion, while sparing as much normal tissue as possible. The authors studied the efficacy of MMS for the treatment of LM and LMM. METHODS: Between 1985 and 1992, 45 patients with LM (26) and LMM (19) were treated with MMS. The authors' technique was to use examination of frozen sections and rush permanent sections (prepared and read within 24 hours). Positive frozen sections warranted further excision. For negative or equivocal frozen sections, surgery was interrupted until the examination of permanent sections was performed. RESULTS: All 45 patients were free of local disease and evidence of metastases at an average of 29.2 months (range, 4-81 months) after therapy. CONCLUSIONS: MMS aided by rush permanent sections yielded a prolonged disease free survival for all 45 patients with LM or LMM. Because the MMS technique minimizes the removal of normal tissue, and the local cure rate in this study was superior to that reported for conventional surgery, the authors recommend this technique for the treatment of LM and LMM. PMID- 8199994 TI - Analysis of melanocytic lesions by DNA image cytometry. AB - BACKGROUND: There is increasing evidence that melanocytic nevi with architectural and/or cytologic atypia (dysplastic melanocytic nevi [DMN]) are lesions intermediate between banal nevi and malignant melanoma. Other studies have shown conflicting results regarding the DNA content in DMN. METHOD: In the present investigation, the authors measured DNA ploidy by image analysis (CAS-200 system, Cell Analysis Systems, Inc., Elmhurst, IL) using Feulgen staining in 54 melanocytic lesions. The lesions were categorized into 7 groups: compound nevus (CN) = 7; compound nevi with features of DMN (F) = 10; DMN with slight atypia = 8; DMN with moderate atypia = 9; DMN with severe atypia (S) = 8; melanoma in situ = 5; and malignant melanoma (CMM) = 7. The age distribution for these various lesions was also recorded. DNA histograms obtained by image analysis from these groups were examined for DNA aneuploidy by DNA index and classified according to Auer classifications (Auer I-IV). RESULTS: There was a progression of mean age for each group of melanocytic lesions, ranging from 39 years for ordinary nevi to 53 years for invasive melanoma. The Type I histogram, which is distinctly diploid, was seen in 4 of 7 cases of CN, 5 of 10 of nevi with features of dysplastic nevus, and 3 of 8 nevi with slight atypia. The Type I histogram was not observed at all in nevi with moderate atypia, severe atypia, melanoma in situ, and invasive melanoma. The Type IV histogram (aneuploid) was not identified in low grade lesions (CN, F, S), but was observed in two of nine nevi with moderate atypia, six of eight lesions with severe atypia, two of five melanomas in situ, and five of six invasive melanomas. Aneuploidy by DNA index was noted in one nevus with features of DMN, one DMN with slight atypia, one with moderate atypia, four of eight DMN with severe atypia, two of five in situ melanomas, and two of six invasive melanomas. CONCLUSION: The results show that DMN exhibit a spectrum of abnormal DNA content intermediate between banal nevi and CMM and that DNA content generally correlates with the age of patients and degree of atypia in melanocytic nevi. PMID- 8199995 TI - Can intraductal breast carcinoma be excised completely by local excision? Clinical and pathologic predictors. AB - BACKGROUND: Microscopic evaluation of excised intraductal breast carcinoma (DCIS) specimens using a serial subgross technique reveals that in many patients the lesion is larger than expected, often making complete excision impossible with less than a true quadrantectomy. Data is presented on 181 patients with DCIS in whom the initial biopsy was performed using a more cosmetic wide local excision rather than a true quadrantectomy. METHODS: Clear margins were defined as no tumor within 1 mm of any inked or dyed margin. All of these patients subsequently underwent mastectomy or reexcision of the initial biopsy site. This allowed pathologic evaluation for residual disease. RESULTS: At mastectomy or reexcision, 76% of patients with initially involved margins had residual DCIS, as did 43% of patients with initially clear margins (P < 0.0001). Larger tumor size was a statistically significant predictor of initial margin involvement and residual DCIS (P < 0.05). Patients with comedo-DCIS had a greater tendency toward positive initial histologic margins and residual DCIS, but this trend was not statistically significant (P < 0.1). CONCLUSION: DCIS presents major problems to both surgeons and pathologists. It is difficult to excise completely using a wide local excision. Histologically negative margins do not guarantee that residual DCIS has not been left behind. Inadequate excision of the primary lesions may be the most important cause of local failure after conservative treatment for intraductal breast carcinoma. PMID- 8199996 TI - Activation of cellular immunity after intracavitary monoclonal antibody therapy of ovarian cancer. AB - BACKGROUND: Murine monoclonal antibodies (MoAbs) are now used for targeted tumor therapy. A major obstacle in their successful application is the development of a humoral antiglobulin response, which limits the use of repeated cycles of therapy. The cellular aspects of that response are not well understood. METHODS: Fifteen patients who had one (12 patients) or two (3 patients) courses of MoAb treatment, 13 age-matched patients with the same histologic types of tumors who had not received MoAbs, and 4 healthy control subjects were studied. Peripheral blood mononuclear cells (PBMCs) were obtained and tested for the ability of T cells to proliferate in vitro in the presence of the MoAb administered for therapy (HMFG1), a control antibody (11.4.1), and, in some cases, their F(ab')2 fragments. In addition, PBMCs from these patients were phenotyped after in vitro MoAb stimulation with antibodies against CD2, CD3, CD4, CD8, CD16, CD20, CD25 (interleukin-2 receptor [IL-2R]), CD45RA, and UCHL1, and the production of interleukin-2 (IL-2) was evaluated by the CTLL-2 bioassay. RESULTS: A dose dependent in vitro T-cell proliferation was observed in 13 of the 15 patients after MoAb therapy. This was not observed in the pretherapy group of patients or healthy control subjects. The mean stimulation index (SI) in the posttherapy group was significantly higher than that of the pretherapy patients and that of healthy control subjects (P = 0.007). When the in vitro T-cell proliferative responses of these patients were measured in the presence of HMFG1 MoAb (IgG1) and 11.4.1 MoAb, there was no significant difference in the mean SI for HMFG1 versus 11.4.1 for the whole group of treated patients (P = 0.67). A significant increase in the mean SI was observed in the presence of HMFG1 over 11.4.1 and their F(ab')2 fragments (P = 0.02) in patients treated twice. A significant increase in the percentage of cells expressing IL-2R was observed after in vitro MoAb stimulation. CD4+ lymphocytes, particularly the CD4+/UCHL1+ memory, the CD4+/IL-2R+ subpopulation, and the CD4/CD8 ratio, increased in all the cases studied after MoAb stimulation, where B-cell and natural killer-cell numbers remained relatively constant (< 2-3%). A sixfold increase was found in the production of IL-2 in PBMC supernatants after MoAb stimulation. CONCLUSIONS: Mouse MoAbs administered to patients with cancer can lead to the generation of T cells, which can recognize these MoAbs as antigens and therefore refocus the host's cellular immune response against the targeted tumor. The main proliferating population appears to be CD4+ T-lymphocytes, which after stimulation can release IL-2. Multiple treatments may lead to the generation of T cells with specificity for the idiotypic component of the administered MoAb. PMID- 8199997 TI - Intratumoral DNA heterogeneity correlated with lymph node involvement and surgical staging in epithelial ovarian cancer by flow cytometry. AB - BACKGROUND: Flow cytometry (FCM)-measured DNA content may be a predictor in the prognosis of ovarian cancer. Multiple specimens taken from the same ovarian tumor may show a variation in DNA content (i.e., intratumoral DNA heterogeneity). We measured the FCM DNA content of multiple specimens from the same tumor in ovarian cancer, and the relationship among DNA ploidy, intratumoral DNA heterogeneity, retroperitoneal lymph node involvement, and surgical staging was evaluated. METHODS: Forty-one patients with primary epithelial ovarian cancer were included in the study. The FCM-measured DNA content of multiple fresh tumor specimens taken from different parts of the same ovarian tumor from each patient was measured. When aneuploidy was observed in at least one specimen from the same tumor, the tumor was defined as an aneuploid tumor. If there were two or more different aneuploid stem lines with a variation of DNA indices (differences of the DNA indices > 0.15) from the same tumor, the presence of intratumoral DNA heterogeneity was defined. RESULTS: Diploid tumor was found in 8 (19.5%) of the 41 patients, and aneuploid tumor with intratumoral DNA heterogeneity was found in 20 (48.8%). None of the eight patients with diploid tumors demonstrated lymph node involvement. In contrast, lymph node involvement was found in 14 (70.0%) of 20 patients with intratumoral DNA heterogeneity. There was a significant different incidence of lymph node involvement between the groups with and without intratumoral DNA heterogeneity (P < 0.01). The incidence of intratumoral DNA heterogeneity significantly correlated with the International Federation of Gynecology and Obstetrics staging (P < 0.01), while that of aneuploid tumor did not. CONCLUSIONS: Intratumoral DNA heterogeneity reflected a malignant potential for lymph node involvement and its progression in epithelial ovarian cancer. PMID- 8199998 TI - Modulation of human lymphoblastoid interferon activity by melatonin in metastatic renal cell carcinoma. A phase II study. AB - BACKGROUND: Numerous attempts to identify active cytotoxic agents for the treatment of metastatic renal cell carcinoma (RCC) have proved disappointing. However, several recent developments in biologic therapy of neoplastic disease have substantially improved the prospects for the treatment of advanced RCC. Melatonin (MLT), a hormone regulated by the pineal gland, has been shown to act on the immune system by causing the release of cytokines from activated T-cell populations. METHODS: A series of 22 patients with documented progressing RCC entered a trial in which the authors studied the effect of a long term regimen (12 months) with human lymphoblastoid interferon (IFN), 3 mega units (MU) intramuscularly 3 times per week, and MLT, 10 mg orally every day. RESULTS: Twenty-one patients were evaluable for response and toxicity. There were seven remissions (33%): three complete, involving lung and soft tissue and four partial, with a median duration at the time of this writing of 16 months. Nine patients achieved stable disease, and five progressed. General toxicity was mild. Fever, chills, arthralgias, and myalgias occurred rarely. Leukopenia and hepatic enzyme elevation were modest and always reversible. CONCLUSIONS: Response rate and toxic effects observed during this study warrant additional randomized studies to define the role of MLT's concomitant administration in the clinical response to IFN in metastatic RCC. PMID- 8199999 TI - The role of pelvic lymphadenectomy and radical cystectomy for lymph node positive bladder cancer. The Memorial Sloan-Kettering Cancer Center experience. AB - BACKGROUND: The impact of pelvic lymph node dissection (PLND) on the survival of patients with lymph node positive bladder cancer is controversial. METHODS: The authors retrospectively analyzed the long term and disease free survival among 140 patients with lymph node positive disease having radical cystectomy and bilateral PLND at the Memorial Sloan-Kettering Cancer Center between 1980 and 1988. They also sought to identify prognostic variables for recurrence and survival. RESULTS: Of the 140 patients, 36 (25.7%) were found to be tumor free, with 22 (15.7%) followed longer than 5 years. Regression analysis identified P category as the only prognostic parameter influencing survival. Patients with tumors confined to the bladder (< or = P3a) had a 52.6% 5-year survival rate compared with 23.4% among those with extravesical (> or = P3b) tumors. N-category was a significant predictor for recurrence but not survival. CONCLUSIONS: As judged from this analysis, radical cystectomy and a systematic PLND alone can provide favorable outcome in some patients with regional nodal metastases from bladder cancer. The survival advantage is most pronounced in patients with low stage primary tumors. Stage migration and patient selection may have biased these findings. PMID- 8200000 TI - Long term results of stereotactic brachytherapy used in the initial treatment of patients with glioblastomas. AB - BACKGROUND: Despite optimal therapy with surgery and radiotherapy, the prognosis of patients with glioblastomas remains poor. Stereotactic brachytherapy involves the accurate placement of radioactive isotopes within brain tumors, significantly increasing the dose of radiation that can be delivered to the tumor bed without substantial risk to surrounding normal tissue, potentially improving local tumor control and patient survival. METHODS: Between February 1987 and July 1993, the authors treated 56 patients with glioblastomas with stereotactic brachytherapy as part of their initial therapy. Patients underwent surgery, limited field external beam radiotherapy, and brachytherapy with temporary high-activity iodine 125 sources, giving an additional 50 Gy to the tumor bed. RESULTS: Median survival for patients undergoing brachytherapy was 18 months compared with 11 months for a matched brachytherapy control group with similar clinical and radiologic features (P < 0.0007). Survival rates at 1, 2, and 3 years after diagnosis of 83%, 34%, and 27%, respectively, for patients receiving brachytherapy were significantly increased compared with survival rates of 40%, 12.5%, and 9%, respectively, for control subjects. Thirty-six patients (64%) underwent reoperation for symptomatic radiation necrosis from 3 to 42 months (median, 11 months) after brachytherapy. The median survival of patients undergoing reoperation was 22 months compared with 13 months for those who did not have further surgery (P < 0.02). Thirty-five percent of patients relapsed locally within the brachytherapy target volume, whereas 65% had marginal or distant relapses. CONCLUSIONS: Brachytherapy may improve local tumor control and prolong survival when used in the initial treatment of selected patients with glioblastomas. PMID- 8200001 TI - Myelopathy after intrathecal chemotherapy. A case report with unique magnetic resonance imaging changes. AB - BACKGROUND: Paraplegia caused by intrathecal chemotherapy has no known pathognomonic features and is a diagnosis of exclusion. METHODS: The authors reported the clinical and neuroimaging findings in one patient with this syndrome. RESULTS: The patient had severe paraplegia with urinary retention and impaired pain and touch sensation below T-10 with sparing of proprioception and vibration sense. Magnetic resonance imaging (MRI) scan showed diminished intensity throughout the central cervical spinal cord. Post-gadopentetate dimeglumine enhancement was scattered throughout the cervical spinal cord and in two areas of the dorsal spinal cord. Axial views of the cervical spinal cord showed that this enhancement was limited to the lateral columns. CONCLUSIONS: The MRI in myelopathy due to intrathecal chemotherapy may show a unique pattern of postgadopentetate dimeglumine enhancement limited to the lateral columns of the spinal cord. However, two recently encountered patients with the same syndrome did not show similar changes. PMID- 8200002 TI - Epstein-Barr virus in patients with polymorphic reticulosis (lethal midline granuloma) from China and Japan. AB - BACKGROUND: Polymorphic reticulosis is one of several diseases constituting lethal midline granuloma (LMG). Previous immunohistochemical studies suggested a T-cell nature of proliferating cells; the term nasal T-cell lymphoma (NTL-LMG) has since been used widely. The authors' previous study in Asian countries showed the clustering of Mongolian patients with NTL-LMG, but the frequency varied with geographic area; it was much higher in Korea and southwest Japan (Okinawa) than in Shanghai and Honshu, Japan. Recently an etiologic role of Epstein-Barr virus (EBV) for the development of NTL-LMG has been postulated. METHODS: In this study, the presence of EBV and human T-cell lymphocytic leukemia virus type 1 (HTLV-1) genomes were examined in NTL-LMG patients from Southwest Japan (Okinawa, 10 patients), another Japanese district (Honshu, 21 patients), and Shanghai, China (5 patients). All of the tissues from different geographic sites were analyzed at one central location. RESULTS: Immunohistochemistry showed that proliferating large cells were positive for CD43 and/or CD45RO, identical with reported NTL-LMG cases. Polymerase chain reaction (PCR) revealed the presence of EBV genome in the NTL-LMG lesions, but the frequency varied according to the geographic area: 67% in Okinawa, 33% in Honshu, and 100% in Shanghai. In situ hybridization provided positive signals in the nuclei of proliferating cells. Expression of latent membrane protein in the proliferating cells of cases positive for EBV by PCR and in situ hybridization was confirmed. CONCLUSIONS: The results suggest that the EBV may play a role in the development of NTL-LMG. However, the variation of frequency of EBV genome in different geographic locations suggests that EBV infection may not be an indispensable condition for the disease. PMID- 8200003 TI - Use of positron emission tomography with fluorodeoxyglucose in patients with extracranial head and neck cancers. AB - BACKGROUND: The purpose of this study was to evaluate the utility of positron emission tomography- (PET) 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) imaging in extracranial head and neck cancers. METHODS: Sixty patients with biopsy-proven cancers were studied using PET-FDG. Thirty-four patients were studied before therapy (staging), of which 15 patients received primary radiotherapy and serial PET-FDG imaging (monitoring). Seven patients with advanced disease had laser excision (monitoring), and 19 patients were evaluated for recurrent disease (recurrence). RESULTS: Four patients had unknown primary lesions. PET-FDG imaging located the primary tumor in two of four patients, and magnetic resonance imaging (MRI) in none of four. In the remaining patients (staging), PET-FDG imaging detected the primary tumor in 29 of 30 patients, and MRI in 23 of 30. In the staging group, PET-FDG imaging identified the presence or absence of lymph node involvement in 32 of 34 patients, and MRI in 31 of 34. PET-FDG imaging was helpful in evaluating tumor response to radiation therapy or laser excision. Ten patients evaluated for recurrent disease had biopsy-confirmed recurrences, and 7 had no recurrence. PET-FDG imaging results were positive for primary tumor recurrence in 9 of 10 patients, and MRI results were positive in 6 of 10. MRI results were negative for lymph node disease in one of these patients with recurrent primary tumor where PET-FDG imaging and biopsy demonstrated nodal involvement. PET-FDG results were negative for recurrent disease in seven of seven patients, and MRI results were negative for recurrent disease in in four of seven. CONCLUSION: In this series, the authors found that PET-FDG is a useful diagnostic modality for evaluating the patient with an unknown primary, monitoring response to therapy, and in detecting recurrent tumors. PMID- 8200004 TI - Posttransplant T-cell lymphoma. Report of three cases and a review of the literature. AB - BACKGROUND: Although 14% of the malignant lymphomas after organ transplantation are reported to be T-cell lymphomas, only a few cases are described in the literature. METHODS: The authors presented three new cases. They summarized the clinical data and analyzed histologic and immunochemical findings. The presence of Epstein-Barr virus (EBV) and human T-cell lymphoma type 1 (HTLV-1) were investigated. T-cell receptor (TCR) rearrangement was analyzed by Southern blot technique in two cases. RESULTS: Two of the three lymphomas developed after renal transplantation. One was a T-cell lymphoma of pleomorphic medium-sized cell type and the other was a T-cell lymphoblastic lymphoma; the third T-cell lymphoma was an anaplastic large cell (Ki-1 positive) type that developed after heart transplantation. No association was established with EBV or HTLV-1. A monoclonal TCR rearrangement was found in the two cases that were analyzed. A literature search revealed 22 other cases. Nineteen of the 22 reported cases were peripheral T-cell lymphomas. Almost all lymphomas presented in extra-nodal sites. The time between diagnosis and organ transplantation seemed to be influenced by the type of immunosuppressive therapy. In five cases, EBV was detected in the tumor cells. A monoclonal T-cell receptor rearrangement was found in eight cases and a polyclonal proliferation in one case. Response to therapy was variable, but often poor. CONCLUSIONS: The etiology of posttransplant T-cell lymphomas remains unclear. Similarities with posttransplant B-cell proliferations are the predominant extranodal presentation and the finding that the time of occurrence is influenced by the type of immunosuppression. In contrast with posttransplant B cell proliferations, only a minority of the cases are associated with EBV. Most tumors appear to be monoclonal. Prognosis is generally poor, but tumor presentation with localized disease might have a somewhat better prognosis. PMID- 8200005 TI - A review of 76 patients with myelodysplastic syndromes treated with danazol. AB - BACKGROUND: Treatment of myelodysplastic syndromes (MDSs) remains unsatisfactory. A limited number of reports provide contradictory information on whether danazol, a synthetic androgen, may be useful in patients with MDS. METHODS: Between 1984 and 1992, 76 patients were treated with danazol (Danatrol, Winthrop) in an open nonrandomized study. Clinical status, blood counts, differential marrow cell counts, transfusion requirements, and liver enzymes were monitored at 3-month intervals during and 6 months after discontinuation of therapy. The authors present the retrospective analysis of this cohort of patients. RESULTS: This study shows a limited usefulness of danazol in patients with MDS. Blood counts were not significantly changed during danazol administration; neither were transfusion requirements. Overall survival and the rate of leukemic transformation were not affected when compared with 50 untreated patients or with data available in the literature. An increase in platelet numbers in four patients and in hemoglobin level in one patient was observed; these patients were unremarkable and were not transfused before initial danazol therapy; therefore, changes in blood counts were of limited clinical significance. The search for subgroups of patients likely to have a favorable response was unsuccessful. Side effects of danazol were limited. In addition, this study provides information on the frequency of antiplatelet antibodies and other autoantibodies in patients with MDS. CONCLUSIONS: This study does not support a positive effect of danazol in patients with MDS during long term follow-up. Anecdotal positive evolution in a few patients cannot be formally ascribed to danazol. These results should be interpreted by comparison with previous publications that report on small numbers of patients with limited follow-up. Based on these data, the authors cannot recommend the systematic use of danazol in MDS. PMID- 8200006 TI - A randomized clinical trial of single-dose versus fractionated-dose dactinomycin in the treatment of Wilms' tumor. Results after extended follow-up. Brazilian Wilms' Tumor Study Group. AB - BACKGROUND: To verify the adequacy of a simplified chemotherapeutic regimen for the treatment of Wilms' tumor (WT), the authors conducted a clinical trial to compare the standard fractionated dose (15 mcg/kg x 5 days) of dactinomycin (AMD) with a single dose (60 mcg/kg x 1 day) administration of the drug. METHODS: From October 1986 to December 1988, 176 WT patients were enrolled in a randomized, multicentric clinical trial conducted by the Brazilian WT Study Group in 38 institutions from 8 states. Patients were randomly assigned to treatment arm A (standard 5-day fractionated AMD administration) or arm B (single high dose AMD administration) in the schedules most appropriate for their stage and histology. Except for the differences in AMD administration, patients were managed by the Third U.S. National WT Study protocol. The endpoints of interest were relapse free and overall survival. Complete follow-up information was obtained until December 1992. RESULTS: After a median follow-up of 47 months, there were no significant differences in survival distributions between treatment arms, using data for all patients or data stratified by disease stage. Relapse free and overall 4-year rates were similar in both groups: 67% and 72%, respectively, in arm A, and 67% and 75%, respectively, in arm B (P = 0.839 and 0.710, respectively). Patients assigned to the simplified arm had cumulatively 1921 fewer hospital days as compared with those receiving the fractionated dose. Hepatic toxicity was observed in only one patient assigned to the divided dose regimen and in none of the single dose group. CONCLUSIONS: WT can be treated using a single dose regimen for AMD administration, thus minimizing the inconvenience for the children and their parents and reducing considerably health care delivery costs. PMID- 8200007 TI - Low frequency of the p53 gene mutations in neuroblastoma. AB - BACKGROUND: The p53 gene frequently is affected by point mutations, rearrangements, or deletions that contribute to the genesis or progression of a wide variety of human adult solid tumors; however, to the authors' knowledge, this gene alteration has not been analyzed in neuroblastoma. METHODS: Genomic DNA samples from 20 children with neuroblastoma, including 16 patients with advanced disease, were screened for the presence of mutations in exons 5-9 of the p53 gene, where over 90% of mutations have been reported to be located in human cancer. The screening technique employed polymerase chain reaction/single-strand conformation polymorphism analysis followed by direct DNA sequencing. RESULTS: Heterozygous mutations were detected in 2 of the 20 cases. A silent mutation (T to G transversion) at codon 172 and a missense mutation (G to T transversion) at codon 259 were found in patients with Stage II and Stage IV disease, respectively. Thus, p53 mutations were found to occur in neuroblastoma, but at a low frequency (2 of 20). CONCLUSIONS: Our data suggest that in a minority of neuroblastomas, p53 gene mutations may play a contributing role in tumorigenesis, but other genes presumably play a major role in this tumor. PMID- 8200008 TI - Death during adulthood in survivors of childhood and adolescent cancer. AB - BACKGROUND: Therapeutic advances have extended survival for most children and adolescents with cancer beyond 5 years from diagnosis. However, excess mortality continues beyond 5 years, and a significant portion results from causes other than the primary cancer. Risk factors for these deaths are not currently known. Thus, the authors studied mortality in a cohort of adult survivors of childhood and adolescent cancer to determine whether survivor characteristics were associated with increased relative risk of death from other causes. METHODS: Using 3255 siblings as control subjects, the authors studied survival in a retrospective cohort study of 2319 adults who were at least 5-year survivors of cancer diagnosed before reaching 20 years of age and between 1945 and 1974 (the NCI Five Center Study). Follow-up occurred between 1980 and 1983 at a mean survivor age of 32 years (range, 21-55 years). RESULTS: Between cohort entry and follow-up, 292 (13%) survivors and 50 (2%) controls died. One-third of the deaths in survivors were from causes other than the primary malignancy. Compared with control subjects, between ages 21 and 40 years, survivors had a more than threefold risk of death from other causes. The relative risk (RR) for death from other causes was greatest for survivors treated with radiation and alkylating agents (RR = 6.1; 95% confidence interval [CI], 3.0-12.4) and for those treated with radiation alone (RR = 3.8; 95% CI, 2.3-6.2; Cox regression analysis containing terms for treatment and cancer diagnosis). CONCLUSIONS: Adult survivors of childhood and adolescent cancer had a higher death rate than their siblings, even after removing the effect of primary cancer as the direct cause. Moreover, death from other causes was most strongly associated with increasing intensity of therapy, and this excess risk did not diminish with increasing age and duration of cancer survival. Because contemporary anticancer therapy is, in general, even more intensive than that received by the survivors described in this study, medical surveillance of cancer survivors is increasingly important to diagnose and treat potentially life-threatening complications that may occur decades after therapy has ceased. PMID- 8200010 TI - [Heart and the brain]. PMID- 8200009 TI - Lymph node metastasis from carcinoma of the distal one-third of the stomach. AB - BACKGROUND: A detailed and thorough pathoanatomic study of lymph node (LN) metastases of adenocarcinoma of the distal one-third of the stomach is lacking. METHODS: From December 1987 to March 1992, 190 patients who underwent radical gastrectomy was analyzed. All LN were dissected and labeled according to the Japanese General Rules for the Gastric Cancer Study. RESULTS: A total of 7052 LN with an average of 37.1 per specimen were removed. LN metastases were encountered in 121 patients (63.7%). The most frequent LN metastases were perigastric, above common hepatic artery, along left gastric artery, and hepatoduodenal ligament. The incidence of LN metastasis varied and was highest when tumor was located close to either curvature and extended to duodenum or midbody. The high incidence of LN metastases in the hepatoduodenal ligament was a unique pathologic feature of adenocarcinoma of the distal one-third of the stomach (P = 0.0012). Univariate and multivariate analysis revealed that depth of cancer invasion was the only factor related to LN metastases. CONCLUSIONS: Cancer in the distal one-third of the stomach had a high incidence of LN metastasis to hepatoduodenal ligament nodes. The LN metastasis is correlated with depth of cancer invasion. PMID- 8200011 TI - [Efficacy and tolerability of simvastatin and omega-3 fatty acid combination in patients with coronary disease, hypercholesterolemia and hypertriglyceridemia]. AB - Patients with ischemic heart disease are often affected by a mixed hyperlipoproteinemia, where a hypercholesterolemia of various severity is accompanied by slight or moderate hypertriglyceridemia (type IIb dyslipidemia). Current epidemiologic evidence suggests that hypertriglyceridemia has not to be disregarded, particularly in certain subgroups of patients. We evaluated the effect of the association of simvastatin 10 mg/day [an hydroxymethyl-glutaryl-CoA (HMG-CoA) reductase inhibitor] and omega-3 polyunsaturated fatty acids (n3-PUFA) in comparison with simvastatin 10 mg/day alone. The subjects undergoing the study were affected by coronary artery disease and showed hypercholesterolemia (LDL cholesterol > 160 mg/dl) and moderate hypertriglyceridemia (serum triglycerides 200-400 mg/dl) after 2 months of moderate dietary therapy for hyperlipidemia (Step 1 of the National Cholesterol Education Program [NCEP]). Thirty-nine patients were randomized to have 1 of 2 scheduled treatments. At the same time the patients underwent severe dietary therapy for hyperlipidemia (Step 2 of the NCEP). After 3 months of treatment, total-cholesterol, LDL-cholesterol, and triglycerides were significantly lower than basal values in both groups (p < 0.05). Total-cholesterol, LDL-cholesterol, and triglycerides were lower in the group treated with n3-PUFA and simvastatin compared to simvastatin alone. However, only for triglycerides was the difference significant (-39.99% in patients treated with n3-PUFA and simvastatin versus -25.65% in patients treated with simvastatin alone, particularly in the first group of 35.85%; p < 0.05). With regard to HDL-cholesterol, the differences between the basal values and the 2 groups of treatments were non significant. Remarkable side effects were not observed in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200012 TI - [Evaluation of aortic distensibility using cine-MR before and after antihypertensive treatment with calcium antagonists and ACE-inhibitors]. AB - Several studies have been performed in the last years to evaluate arterial distensibility, particularly of the aorta, in hypertension and to estimate the changes of this distensibility after anti-hypertensive treatment. The aim of this study was to assess the aortic distensibility in a group of 10 patients with essential hypertension in comparison with a control group, with regard to the vascular effects of a long-term anti-hypertensive treatment with calcium antagonists and ACE-inhibitors. All patients were studied using cine-MR imaging, a technique with several peculiarities (multiplanar scanning, intrinsic contrast, etc) that allows simple and quick assessment of the aortic vascular parameters in the ascending and descending tracts. The results of our study show the absence of a significant improvement of aortic vascular areas, and therefore of vessel distensibility, even in the presence of a complete blood pressure normalization in all patients after a 3-month treatment. These data do not confirm previous reports in this setting, based on the ultrasonographic techniques (2D and Doppler echocardiography). Two major reasons may explain our results: first, the rigorous criteria of patient enrollment that we have stated in order to avoid any influence of age and/or other pathologies; second, the ability of MR imaging to allow accurate estimation of aortic vascular parameters and to achieve an excellent intraobserver and interobserver reproducibility in comparison with other techniques. We conclude that MR imaging is the method of choice for the assessment of cardiovascular function and morphology. PMID- 8200013 TI - [Diastolic flow in the left ventricle of healthy subjects: a study using processing of intracardiac color-Doppler maps]. AB - Aim of the study was to evaluate the left ventricular (LV) diastolic flow propagation. Ten healthy subjects (28 +/- 6 years) were examined. Two-dimensional echocardiography and color-Doppler at mitral valve were performed. A cine-loop was transferred on-line to a color image processor. Selected digitized images were stored on microdisk. LV end-diastolic, end-systolic and early filling (EF) volumes were measured. Doppler measurements across the mitral valve were obtained: peak E, peak A, E/A, the integral (VTI) of E and A, acceleration and filling time. Extension of color and time base to apex, time of EF and atrial filling (AF) were obtained by M-color, along the base-apex axis. On frames of EF and AF of 2D-color, diastolic maps were processed: surface area and pixel velocity, mean (mv) and peak (pv), were obtained of the entire color area and of 4 selected areas, 2 mm wide: 1 along the annulus-apex axis (LAx), and 3 transverse, planes, at the annulus, at papillary (1/3) and at the apex (2/3 of LAx). Three-dimensional plot and velocity distribution were obtained. Values of pixel of the entire color area were stored on microdisk and processed using a Macintosh PC. For each transverse section, 1 pixel wide, mv and pv were obtained, and data were referred to normalized axis and the mean was calculated. RESULTS: end-diastolic volume index (EDVI): 66 +/- 7, end-systolic volume index (ESVI): 26 +/- 5 ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200014 TI - [Pulmonary venous flow in atrial fibrillation evaluated by transesophageal Doppler echocardiography]. AB - Pulmonary venous flow (PVF) can be recorded by transesophageal echocardiography. In normal subjects the PVF is triphasic with 2 peaks in systole and 1 peak in diastole. At atrial contraction it is possible to record a reversal flow (A wave). The evaluation of PVF pattern in patients in atrial fibrillation can better explain the role of atrial contraction. We considered 18 patients with chronic atrial fibrillation with transesophageal Doppler echocardiography. Then we compared the pattern obtained from patients with atrial fibrillation with the normal pattern. During atrial fibrillation we observed a flow reversal during early systolic period. The diastolic wave was increased and prolonged. We also observed that the A wave seems to disappear. The loss of atrial contraction deeply modifies the Doppler PVF. PMID- 8200015 TI - [Rational bases of the use of arterial bypasses in coronary surgery. II. Biochemical-pharmacological evidence]. PMID- 8200016 TI - [Heart involvement in thymic neoformations: the role of magnetic resonance tomography. Experience in 3 cases]. AB - Three paracardiac masses (1 thymic cyst, 2 thymomas) were studied by magnetic resonance imaging (MRI) using spin-echo, multi-echo, and gradient-echo sequences (cine-MR). MRI showed: a pedunculate cystic lesion, typical for thymic origin, in Case 1; cardiac and pulmonary infiltration, and 3 intracardiac metastases, in Case 2; cardiovascular compression but not infiltration, in Case 3. In 3/3 cases MRI was superior to transthoracic echocardiography (TTE), and in 2/2 MRI was superior to computed tomography (CT), not performed in Case 2 (allergy to contrast agents). MRI may be considered the most important technique to evaluate cardiovascular involvement by thymic neoplasms. MRI should be performed after TTE and makes CT unnecessary. PMID- 8200017 TI - International Headache Society classification: interobserver reliability in the diagnosis of primary headaches. AB - We assessed interobserver reliability of the International Headache Society (IHS) classification for diagnosis of primary headaches. The study was performed on 103 patients consecutively seen at two Headache Centres. Each patient was given a structured interview recorded on videotape. Four experienced clinicians then reviewed the interviews separately and made a diagnosis of headache according to IHS criteria at the one- and two-digit levels. At both the one- and the two-digit level the agreement was substantial (Kappa = 0.74 and 0.65, respectively). The analysis of reliability for each of nine items necessary for diagnosis showed an agreement ranging from substantial (Kappa = 0.69) to almost perfect (Kappa = 0.89). Our results indicate that the IHS classification has a good reliability for the diagnosis of primary headaches at the one- and two-digit levels. PMID- 8200019 TI - Chronic daily headache--one disease or two? Diagnostic role of serum ionized magnesium. AB - The entity of chronic daily headache (CDH) is well documented, but is not included in the current classification. We divided patients with CDH into groups with and without migrainous features. This division resulted in clearly distinguishable syndromes of daily migrainous headaches (DMH) and daily tension type headaches (DTH). Family history of headaches was more common in patients with DMH. Patients in both groups had a high incidence of caffeine or drug overuse. The clinical division into DMH and DTH was supported by our finding of a higher incidence of disturbed magnesium (Mg) metabolism in patients with DMH. Of 26 patients with DMH, 8 (30.8%) had low serum ionized, but not total, Mg levels, and 16 (61.5%) had high ionized calcium/magnesium ratios. The corresponding numbers for the 22 patients with DTH were 1 (4.5%) and 8 (36.4%). These new laboratory measurements offer possible biological markers for the diagnosis of different headache syndromes. PMID- 8200018 TI - Abnormal platelet mitochondrial function in patients affected by migraine with and without aura. AB - To investigate energy metabolism in migraine, we determined platelet mitochondrial enzyme activities in 40 patients with migraine with aura and in 40 patients with migraine without aura during attack-free intervals and in 24 healthy control subjects. NADH-dehydrogenase, citrate synthase and cytochrome-c oxidase activities in both patient groups were significantly lower than in controls (p < 0.01), while NADH-cytochrome-c-reductase activity was reduced only in migraine with aura (p < 0.01). No alteration in succinate-dehydrogenase was observed. Monoamine-oxidase activity differed between sexes (p < 0.05) but within each sex group no difference was observed between patients and controls. We hypothesize that the defect in mitochondrial enzymes observed indicates a systemic impairment of mitochondrial function in migraine patients. PMID- 8200020 TI - Intracellular and plasma magnesium in familial hemiplegic migraine and migraine with and without aura. AB - Familial hemiplegic migraine (FHM) is an autosomal dominant type of migraine and probably represents the most extreme end of migraine with aura. Reduced magnesium facilitates the development of spreading depression and possibly aura. Cellular magnesium levels are under genetic control. We hypothesized that FHM patients would have significantly reduced intracellular magnesium levels. We determined intracellular and plasma magnesium levels in blood of 38 afflicted and 11 non afflicted members of three families with FHM and in 32 migraine patients (9 with and 23 without aura) and 32 age and sex matched healthy controls. We found no significant differences between the magnesium levels in the five study groups. We conclude that reduced blood magnesium is unlikely to be related to migraine pathophysiology. PMID- 8200021 TI - On headache and cerebrovascular disease. PMID- 8200022 TI - Evaluating the IHS criteria. PMID- 8200023 TI - Head pain in non-traumatic carotid artery dissection: a series of 65 patients. AB - In order to assess the prevalence and characteristics of cephalic pain in internal carotid artery (ICA) dissection, and to compare clinical and angiographic features of patients with painful and non-painful dissections, we observed 65 patients with angiographically diagnosed extracranial ICA dissection from 1972 to 1990. Forty-eight patients (74%) complained of a cephalic pain which was inaugural in 38 (58.5%). It was homolateral to the dissection in 79% of cases and lasted from 1 h to 30 days, with a median of 5 days. Signs of cerebral or retinal ischemia were observed in 79% of patients, often delayed and occurring up to 29 days after the onset of pain. A painful Horner's syndrome was present in 31% of patients, and was the only manifestation of dissection in 16%. The clinical presentation of the dissections and angiographic findings were similar in patients with and without pain except for a past history of migraine which was more frequent in patients with painful dissections. Cephalic pain is frequent and often inaugural in carotid dissection. Its recognition is important for early diagnosis and treatment. PMID- 8200024 TI - Headache in acute cerebrovascular disease: a prospective clinical study in 240 patients. AB - To evaluate the clinical features of headache in stroke, a prospective study was carried out in 240 consecutive patients with acute stroke who had intact expressive function. Headache occurred in 38%: 32% of 195 patients with ischemic stroke and 64.5% of 45 patients with hemorrhagic stroke (p < 0.0001). Headache patients were younger (mean age 62 +/- 15 vs 67 +/- 11.5 years) than non-headache patients (p < 0.01). A history of previous vascular or tension-type headache was found in 40.5% of the headache group, but in only 23.5% of the non-headache group (p < 0.01). In ischemic stroke, headache was observed in 41% of thrombotic infarcts, in 39% of cardioembolic infarcts, in 23% of lacunar infarcts and in 26% of TIA. Headache was significantly more common in thrombotic than lacunar infarcts (p < 0.05). In hemorrhagic stroke, headache was observed in all subarachnoid hemorrhages and in 58% of intraparenchymal hemorrhages. In ischemic stroke, the mean duration of the headache was 25 +/- 28 h and in hemorrhagic stroke 64.5 +/- 36.5 h (p < 0.00001). In ischemic stroke the headache was focal in 74% and mild or moderate in intensity in 74%. In hemorrhagic stroke, it was diffuse in 52% and the pain intensity was incapacitating in 70%. Headache was more common in vertebrobasilar stroke (59%), in comparison with carotid stroke (26%) or stroke of unclear vascular topography (33%) (p < 0.00001). Fifty-six and a half percent of patients with cortical stroke had headaches, as opposed to only 26.5% of patients with subcortical stroke (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200025 TI - EEG features in juvenile migraine: topographic analysis of spontaneous and visual evoked brain electrical activity: a comparison with adult migraine. AB - Topographic analysis of spontaneous and steady-state visual evoked brain electrical activity was carried out between attacks in 82 migraine patients (40 youths and 42 adults). In adult migraine with aura a significant increase of delta rhythm percentage power was observed compared with migraine without aura and age-matched controls. Children suffering from migraine both with aura and without aura had an increased theta rhythm compared to normal controls. The presence of alpha interhemispheric asymmetry discriminated between migraine with aura and without aura, just as in adults. An increased amplitude of the SVEP F1 component with a tendency to the spread of visual reactivity was observed in juvenile migraine with and without aura; this pattern was not dissimilar from the one previously observed in adult migraine with and without aura. Abnormal photic driving in migraine is independent of age and type of migraine. PMID- 8200026 TI - Opiate and opioid use in patients with refractory headache. AB - Opiate and opioid analgesics are commonly used for pain in general and presumably for headache. Codeine, oxycodone and propoxyphene, among the most commonly prescribed, do carry some risk of abuse, and their efficacy in headache patients has not been well studied. In many patients with other kinds of pain, however, both of neoplastic and non-neoplastic origin, chronic opiate use has been demonstrated to be of benefit without adverse side effects. The type of headache patient with intractable pain who needs frequent opiate analgesic and who does not develop addiction or drug abuse is an important subject for research. PMID- 8200027 TI - Self-treatment of acute migraine with subcutaneous sumatriptan using an auto injector device: comparison with customary treatment in an open, longitudinal study. AB - In a multicenter open longitudinal clinical trial where 479 patients suffering from migraine with or without aura were recruited, patients treated at home one to three migraine attacks with their customary treatment, and subsequently, over a 3-month period, one to three migraine attacks with 6 mg sumatriptan sc using an autoinjector. The headache response to customary treatment was 19% at 1 h and 30.5% at 2 h, and was not significantly different when only attacks treated "adequately" according to accepted treatment recommendations were considered: 16% at 1 h and 35% at 2 h. In contrast, 69% and 82% of patients treated with 6 mg sumatriptan sc had mild headache or no headache at 1 and 2 h respectively, regardless of migraine type or duration of symptoms prior to treatment. Other migraine symptoms (nausea, vomiting, photo- and phonophobia) were effectively treated with sumatriptan. Recurrence of migraine was observed in 31% of patients and was well controlled by a second injection of sumatriptan. It is concluded that 6 mg sumatriptan sc, self-administered using an autoinjector, is well tolerated and more effective than most currently used acute treatments for migraine in a population of severely affected patients consulting a neurologist. PMID- 8200028 TI - Handedness and headache. AB - A California handedness study involved 199 male and 74 female cluster headache sufferers as well as 477 migraineurs. Earlier reported data indicated that cluster headache patients had a left-handedness prevalence of over 15%. With the current data the prevalence in males was 11.0% and in females, 8.2%. The corresponding migraine figures were 11.8% and 8.1%. The cluster and migraine headache groups did not differ significantly from each other or from the expected 10% frequency of left-handedness in either sex. PMID- 8200029 TI - Activation of rat basophilic leukemia cells by epsilon BP, an IgE-binding endogenous lectin. AB - IgE-binding protein (epsilon BP) is a beta-galactoside-binding animal lectin identified by its affinity for IgE. We have reported that epsilon BP also binds the mast cell high-affinity IgE receptor (Fc epsilon RI), via lectin-carbohydrate interaction. We have now studied the physiological significance of epsilon BP-IgE Fc epsilon RI interactions in mast cell activation using rat basophilic leukemia (RBL) cells as the model system. We report here that both unsensitized and IgE sensitized RBL cells are activated upon exposure to epsilon BP-coated surfaces. Activation of RBL cells by the lectin epsilon BP can be significantly inhibited by appropriate saccharides. Exposure of RBL cells to epsilon BP-coated surfaces caused cell spreading similar to that caused from adherence to fibronectin-coated surfaces. However, epsilon BP by itself caused mediator release whereas fibronectin only potentiated antigen-mediated activation of RBL cells. Under appropriate conditions, epsilon BP, therefore, has the potential to activate mast cells culminating in augmentation of an inflammatory response. PMID- 8200030 TI - Leukotriene B4 enhances IL-4-induced IgE production from normal human lymphocytes. AB - Interleukin 4 (IL-4)-induced IgE production by normal peripheral blood mononuclear cells (PBMC) and E- cells (PBMC partially depleted of T cells) was significantly enhanced by leukotriene B4(LTB4) in a dose-dependent manner, whereas LTB4 by itself was not effective for IgE production. The potentiating effect of LTB4 was strictly dependent on IL-4. When PBMC or E- cells were primed with IL-4 (300 U/ml) for 48 hr, then recultured with LTB4 alone (10(-10) to 10( 8) M), increased IgE production was observed. Maximum enhancement of IgE production after IL-4 priming was achieved using a combination of IL-4 and LTB4, acting additively. Moreover, the potentiating effect of LTB4 on IL-4-induced IgE production was completely dependent on the presence of a monocyte/macrophage population. This effect of LTB4 was completely abolished by depletion of monocytes and recovered by reconstitution with autologous monocytes. From the study of IL-4 receptor (IL-4R) expression determined by flow cytometry, IL-4 was found to upregulate the biotinylated-IL-4 (B-IL-4)/streptavidin binding to both T and B-cell populations. A further increase of B-IL-4 binding was obtained when the cells were incubated with IL-4 and LTB4. Finally, LTB4 can induce soluble CD23 (sCD23) release by E- cells tested either alone or in the presence of IL-4. Taken together, these data suggest that LTB4 can influence the IL-4-induced IgE production through, at least, a bimodal action, i.e., increase of IL-4R positive cells and release of sCD23. These findings may be a specific feature of LTB4 which provides a crucial role in IL-4-linked allergic inflammatory process. PMID- 8200031 TI - Contribution of host radioresistant T cells to the clonal elimination of minor lymphocyte stimulatory-1a reactive T cells in mouse bone marrow chimeras. AB - When bone marrow (BM) cells from I-E+ and minor lymphocyte stimulatory (Mls) antigen (Ag) disparate mice (Mls-1b) were transplanted to lethally irradiated Mls 1a mice, Mls-1a reactive T cells were found to be completely deleted from the developing thymocyte population in these [Mls-1b-->Mls-1a] radiation chimeras. It has been shown that BM-derived class II (Ia) positive cells play an essential role in this clonal deletion. Thus, Mls-1a Ag appeared to have been transferred from recipient cells to the Ia+ cells derived from donor BM. These Mls-1a-Ia complexes appear to be responsible for elimination of the Mls-1a reactive T cells that have also been derived from donor BM. However, definition of the cells of the recipient that generate the Mls-1a Ag and transfer them to the BM-derived Ia+ cells has remained unclear to date. In the analysis described herein, we have investigated the tolerogenicity of Mls-1a Ag derived from host T cells which represent a major population of radioresistant cells in the [Mls-1b-->Mls-1a] chimeras. When recipient T cells that had been collected and purified from spleens of [Mls-1b-->Mls-1a] chimeras were administered i.v. into [Mls-1b] chimeras, Mls-1a reactive V beta 6+, V beta 8.1+, or V beta 9+ T cells were completely eliminated. Thus, residual radioresistant host T cells present in the radiation BM chimeras are the cells which produce the Mls-1a Ag. These Mls-1a Ags ultimately contribute to the clonal elimination of Mls-1a reactive T cells from the developing thymocyte population. The present findings indicate that recipient T cells which can survive lethal irradiation and produce intrinsic superantigens alter eventually the T cell repertoire in the thymus which have been developing from precursors of donor BM. PMID- 8200032 TI - Synthetic peptides of human CD4 enhance binding of immunoglobulins to monocyte/macrophage cells. II. Mechanisms of enhancement. AB - We have previously shown that a synthetic peptide corresponding to amino acid residues 21-49 of the first extracellular domain of human CD4 binds immunoglobulins (Ig) and antibody: antigen (Ab:Ag) complexes, and greatly enhances the uptake of aggregated Ig by monocyte/macrophage U937 cells. In this report, we investigated the mechanisms of enhanced uptake, and the contribution of different receptors present on the surface of monocyte/macrophage cells to this phenomenon. Our results indicate that both Fc receptor (FcR) and cell surface CD4 participate in the enhanced uptake of Ig promoted by the synthetic peptide of CD4. The involvement of these two receptors was demonstrated in experiments using monoclonal antibodies to FcR and CD4, as well as monosialoganglioside GM1, a substance known to modulate surface CD4. The participation of CD4 was further confirmed using the CD4 monocyte/macrophage cell line MM-6. Together, the results of these experiments indicate that surface CD4 may cooperate with FcR in handling aggregated Ig and Ab:Ag complexes. The implications of these findings for immunoregulation by Ab:Ag and idiotype:anti idiotype (Id:anti-Id) complexes, and infection of macrophages by HIV, are discussed. PMID- 8200033 TI - Monoclonal antibody 2B6-F2 identifies a subset of murine natural killer cells with receptors for YAC-1 and WEHI-164 targets. AB - This study reports the generation of rat MoAb 2B6-F2 (IgG2a) that identifies a subpopulation of murine NK cells in the spleen, bone marrow, peripheral blood, lung, and peritoneal leukocytes. By flow cytometry, 2B6-F2 reacted with 10% of naive CBA (immunizing strain) spleen leukocytes of which 3% exhibited small lymphocyte morphology while 7% were large granular leukocytes. This pattern of binding was similarly obtained for BALB/c, C57BL/6, CE, and DBA/2 mice. 2B6-F2 and complement reduced splenic NK activity 40-57% in CBA, C57BL/6, BALB/c, CE, and DBA/2 strains. In CBA, C57BL/6, and CE mice < or = 15% reduction in splenic NC activity was observed while DBA/2 and BALB/c mice displayed 55-73% reduction. Cellular competitive inhibition studies showed that 2B6-F2+ NK cells in BALB/c and DBA/2 mice bind and kill YAC-1 and WEHI-164 target cells via a receptor that recognizes a shared determinant on these targets. Western blot and radioimmunoprecipitation studies indicated that 2B6-F2 identifies a 14-kDa monomeric cell surface molecule. PMID- 8200034 TI - Induction of Ly-49 on an interspecies hybridoma between differentiation stage specific murine T cells and a rat T lymphoma. AB - Ly-49 can be expressed in interspecies hybridoma cells resulting from the fusion of Ly-49 negative lymphoid cells from normal mice and Ly-49 negative T cells from the rat thymoma W/Fu(C58NT)D (C58). Several hundred hybridoma clones of this type were studied. Hybridoma clones derived from the fusion between activated C57BL/6 mouse spleen cells and C58 expressed Ly-49 on their surface although Ly-49 was undetectable on both parental cells. No Ly-49 antigen was expressed on hybrids when BW5147, a T lymphoma derived from AKR mouse, replaced C58 as parental cell. Thymocytes from C57BL/6 mice also produced Ly-49 positive interspecies hybridomas with C58. Subsequent manipulation of these thymocytes with a mixture of anti-CD4 and anti-CD8 antibodies plus complement to obtain double negative cells (CD4-/CD8 ) prior to the fusion abolished the expression of Ly-49 on hybridomas. On the other hand, if the thymocytes were treated with either anti-CD4 or anti-CD8 antibody plus complement, the resultant thymocytes which were a mixture of cells with a single positive (CD4+/CD8- or CD4-/CD8+) and a double negative phenotype (CD4-/CD8-) retained the ability to produce Ly-49 positive hybridomas. Interspecies hybridomas between either CD4+/CD8- or CD4-/CD8+ functional T cell clones and C58 expressed Ly-49 on their surface, though these parental T cells lacked Ly-49 on their surfaces. Northern hybridization analysis using Ly-49 cDNA revealed that C58 cells do not express Ly-49 mRNA, indicating that a trans-acting factor(s) from C58 plays an important role in the induction of cell surface Ly-49 expression on interspecies hybridomas. Our data indicate the complex nature of the regulatory mechanisms for expression of the Ly-49 molecule. PMID- 8200035 TI - Regulated expression of integrins and other adhesion molecules during differentiation of monocytes into macrophages. AB - Monocyte/macrophages adhere to cells (lymphocytes, vascular endothelial and other cell types) and to extracellular matrix components (fibronectin and laminin) by using specific cell surface adhesive structures. In the present study we have analyzed expression of integrins, immunoglobulin (Ig)-related, selectins, and other adhesion molecules on blood monocytes, in vitro differentiated macrophages (ivMs), and alveolar macrophages (AMs), obtained from healthy nonsmokers by bronchoalveolar lavage (BAL). We have also investigated expression of adhesion molecules on myelomonocytic cell lines HL-60, THP-1, KG-1, and U937 before and after tetradecanoyl phorbol acetate (TPA)-induced differentiation. With regard to the integrin family, monocytes expressed beta 1 (CD29), alpha 4, alpha 5, alpha 6, beta 2 (CD18), CD11a, CD11b, and CD11c subunits, but not alpha V (CD51). Some reactivity with mAbs against the platelet antigens CD41b (IIb) and CD61 (beta 3) was detected. The Ig-related molecules CD54 (ICAM-1), ICAM-2, and CD58 (LFA-3) were expressed, as well as L-selectin and the carbohydrate ligands Le(x) (CD15) and sialyl Le(x). Immunolabeling for the structurally unrelated molecules CD44 and CD36 was strongly positive. In comparison to monocytes, AMs showed much lower expression of alpha 4, alpha 6, beta 2, CD11a, CD11b, L-selectin, Le(x), and sialyl Le(x). Moreover, ICAM-2 and CD36 were practically absent whereas expression of alpha 3, but not of CD11c, was higher. Similar results were obtained with ivMs. All four myelomonocytic cell lines showed down-regulation of alpha 4 and up-regulation of CD11c after TPA treatment. These findings indicate that maturation of monocytes into macrophages is accompanied by characteristic changes in adhesion molecule expression. The particular array of adhesion molecules on monocytes and macrophages may account for differences in the functional properties of these cells. PMID- 8200036 TI - Intestinal mucosal lymphocytes have H1 receptors: H1 antagonists reduce their proliferation and cytotoxicity. AB - Histamine and H1 antagonists inhibit the proliferation and natural killer activity of peripheral blood mononuclear cells, which express large numbers of H1 receptors. This study examined the presence of H1 receptors and the effects of histamine, H1 antagonists (pyrilamine and diphenhydramine), and H2 antagonists (cimetidine and ranitidine) on human intestinal lymphocyte proliferation and cytotoxicity. Intestinal lymphocytes were obtained by chemical and enzymatic treatment of surgical specimens and purified by Percoll density gradient centrifugation. Proliferation was measured by [3H]thymidine incorporation of mitogen-stimulated lymphocytes; cytotoxicity was measured by the standard 51Cr release assay using HT-29 adenocarcinoma target cells. Scatchard analysis of radioligand binding using [3H]pyrilamine demonstrated H1 receptors. The mitogen induced proliferative responses of intraepithelial lymphocytes and lamina propria lymphocytes were inhibited by histamine and the H1 antagonists but not the H2 antagonists. Cytotoxic activities of fresh or IL-2-stimulated mucosal lymphocytes (spontaneous and lymphokine-activated killing, respectively) were also reduced by the H1 antagonists. A large number of H1 receptors were found on intraepithelial lymphocytes and peripheral blood mononuclear cells and still more on lamina propria lymphocytes. Intestinal lymphocytes bear H1 receptors; histamine and H1 antagonists have immunomodulatory effects on these cells. PMID- 8200037 TI - A monoclonal antibody to the Hodgkin's disease-associated antigen CD30 induces activation and long-term growth of human autoreactive gamma delta T cell clone. AB - In order to identify cell surface structures involved in the activation and growth of human-cloned T lymphocytes, we developed monoclonal antibodies against an autoreactive TcR gamma delta-bearing clone termed DS6. Antibodies were screened for their agonistic properties with the immunizing T cell clone. In the present report, we describe a CD30 mAb, termed BY88, that was capable of inducing, in a short-term assay, a strong proliferation of the T cell clone DS6 when added in combination with IL2 or phorbol myristate acetate. More important was the finding that in the total absence of feeder cells, BY88 mAb and recombinant IL2 were capable of maintaining long-term growth of DS6 cells. As this finding could not be extended to alloreactive cloned T lymphocytes, it is suggested that activation of T lymphocytes through the CD30 molecule is restricted to a T cell subset including autoreactive TCR gamma delta-bearing lymphocytes. PMID- 8200038 TI - B lymphocyte immunoglobulin receptor desensitization is downstream of tyrosine kinase activation. AB - Resting mature B cells have two classes of immunoglobulin receptors on their surface, IgD and IgM. Activation of a cell by crosslinking one of these receptors leads to homologous and heterologous receptor anergy as judged by the inability to induce a second calcium signal 2 hr after the initial activation step. The mechanism for this energy is not known. In this report we show that this receptor anergy is downstream of tyrosine kinase activation in that cells pretreated with anti-IgM, when stimulated with anti-IgD, showed tyrosine phosphorylation comparable to that of naive cells, but had no calcium response. PMID- 8200039 TI - Bovine milk lymphocytes display the phenotype of memory T cells and are predominantly CD8+. AB - The phenotype of bovine milk lymphocytes was investigated and compared to peripheral blood lymphocytes using monoclonal antibodies specific for bovine leukocyte differentiation antigens and flow cytometry. T lymphocytes traffic selectively into bovine milk while B lymphocytes represent a minor population in milk by comparison to peripheral blood. The vast majority of T cells in milk express alpha beta T cell receptors and are predominantly CD8+. T cells in milk express twofold higher levels of CD2 and fivefold lower levels of CD45R, characteristics associated with memory T cells. Grouping of cows by lactational stage and analysis of lymphocyte subpopulation percentages indicated that CD4+ T cells are present in relatively low numbers in milk of cows in the first 50 days of lactation and have a significant tendency to increase in number as lactation progresses. PMID- 8200040 TI - IFN-gamma IL-2, and IL-4 mRNA expression in the skin and draining lymph nodes of BALB/c mice repeatedly infested with nymphal Ixodes ricinus ticks. AB - The skin and draining lymph nodes of BALB/c mice were examined for IFN-gamma, IL 2, and IL-4 mRNA expression by in situ hybridization in three successive infestations with nymphal Ixodes ricinus ticks. IFN-gamma and IL-2 mRNA positive cells were readily detected in lymph node sections during primary antigenic stimulation (72 hr post-tick attachment), whereas hybridization with IL-4 probe yielded no or only a faint positive signal. No changes in the cytokine pattern were observed in lymph node sections from reinfested mice, with IL-4 mRNA always being expressed to a lesser extent than IFN-gamma and IL-2 mRNA. Seventy-two hours post-tick attachment in primary infestation, some infiltrating cells in the skin were positive for IFN-gamma and IL-4 mRNA, but not for IL-2 mRNA. In skin sections of reinfested mice, mRNA coding for IFN-gamma, IL-2, and IL-4 were detected in infiltrating cells. Cells positive for IL-4 mRNA were lower in number than those positive for IFN-gamma and IL-1 mRNA. A significant decrease in the number of IL-4 mRNA positive cells in the tertiary infestation was noted. All together, these results indicate that I. ricinus nymphal ticks antigens are able to elicit expression of IFN-gamma, IL-2 mRNA and to a lesser extent IL-4 mRNA in both skin and draining lymph nodes. In addition, repeated infestations with ticks led to strong expression of IFN-gamma and IL-2 mRNAs in the skin that may be correlated with previous observations showing the occurrence of cutaneous delayed type hypersensitivity in tick-infested mice. Notably, the cytokine pattern observed in the skin and draining lymph nodes is not associated with a protective immune response in mice against I. ricinus nymphal ticks infestations. PMID- 8200041 TI - BCG-induced immunomodulation of DTH to heterologous erythrocytes leads to Mac-1 independent myelomonocytic cell recruitment. AB - BCG(mycobacterium bovis)-modulated delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) differs from that in nonmodulated mice with respect to kinetics of expression, cellular composition of inflammatory foci, and susceptibility to specific suppressor mechanisms. We investigated whether the differences between these two types of SRBC-specific DTH reactions are based on different T cell subpopulations involved or on differences in the mechanisms of myelomonocytic cell recruitment induced by the same T cell subset. We demonstrate that both types of DTH are exclusively mediated by CD4+ T cells, but significantly differ in the mechanisms of inflammatory cell extravasation. While the expression of nonmodulated DTH to SRBC is markedly inhibited by anti-Mac-1 mAb 24 hr after challenge, the BCG-modulated DTH is totally resistant to such treatment. Thus, BCG modulation of the DTH response to SRBC most probably results in the generation of qualitatively different, antigen-specific CD4+ T cells, which induce the activation of adhesion molecules able to circumvent the Mac-1 dependency of the nonmodulated skin response. PMID- 8200042 TI - Human peripheral gamma delta T cells are stimulated by Daudi Burkitt's lymphoma and not by any other Burkitt's lymphoma tested. AB - Daudi Burkitt's lymphoma cells have molecules on their surface which can stimulate proliferation of human gamma delta T cells, while Raji, another Burkitt's lymphoma, cannot stimulate human gamma delta T cells. Human peripheral gamma delta T cells, coexpressing the V gamma 9/V delta 2 chains of the T cell receptor, lyse Daudi cells but not Raji cells. Here, we have screened four other Burkitt's lymphoma cell lines (HH514, DG75, Ramos, and Wilson), as well as cells derived from a fresh Burkitt's lymphoma, to see if any of them can be recognized by human gamma delta T cells. Leukemia-derived lines MOLT-4, CEM, and K562 have also been included in these studies. Among the Burkitt's lymphomas tested, only Daudi, DG75, and HH514 could be lysed by V gamma 9/V delta 2+ T cell clones derived from the peripheral blood of healthy donors. These T cell clones were also able to lyse the NK sensitive leukemia lines K562 and MOLT-4. When bulk cultures of peripheral blood mononuclear cells from healthy donors were cultured with different Burkitt's lymphoma or leukemia cell lines, only Daudi stimulated the outgrowth of gamma delta T cells. Similarly, only Daudi cells could stimulate proliferation of gamma delta T cell clones, and the response was enhanced significantly in the presence of interleukin-2. These data and our prior observations showing the use of the V gamma 9/V delta 2 TCR type by Daudi reactive human gamma delta T cells indicate that Daudi cells are not representative of other Burkitt's lymphoma cell lines. PMID- 8200043 TI - Sea star factor blocks development of T-dependent antibody secreting clones by preventing lymphokine secretion. AB - Sea star factor (SSF), a protein of 39 kDa purified from macrophage-like coelomocytes of the echinoderm Asterias forbesi, has potent immunosuppressive effects on T-dependent but not T-independent antibody responses in vivo. SSF at a concentration of 0.5 microgram/ml markedly inhibits T-dependent antibody production in vitro by fluorescein (Flu)-specific B cells responding in clonal microculture to antigenic stimulation with Flu-conalbumin via the conalbumin specific T cells D10.G4.1 (D10). At this concentration of SSF, Ig secretion induced by a T cell-independent stimulus, lipopolysaccharide (LPS), is not affected. Inhibition of antibody production in T-dependent microcultures by SSF can be completely overcome in a dose-dependent fashion by addition of lymphokine rich supernatants from stimulated cultures of D10 cells. The possibility that SSF suppresses production of requisite cytokine growth factors from T cells was substantiated by the finding that SSF diminishes concentrations of stimulatory cytokines detectable in supernatants from antigen-stimulated cultures. Nevertheless, levels of intracytoplasmic mRNA for IL-4 and IL-5 are not detectably altered by concentrations of SSF that suppress antibody production. Furthermore, when cultures of D10 cells stimulated in the presence of SSF are subjected to freezing and thawing to release intracytoplasmic lymphokines, total levels of stimulatory cytokines are not lower than those in cultures without SSF. These results suggest that SSF inhibits antibody responses by limiting the availability of lymphokines produced by helper T cells. The mechanism for this inhibition may involve either direct effects of SSF on T cells or a block in effective T cell-B cell interaction. PMID- 8200044 TI - Leukocytes migrate through three-dimensional gels of midcycle cervical mucus. AB - The migration of leukocytes through mucus must be an essential factor in the mucosal immune response, particularly during mucosal invasion by pathogens. We used two methods to evaluate the ability of neutrophils to migrate through human midcycle cervical mucus: (i) direct visualization of cell migration within freshly collected mucus samples and (ii) quantification of cell penetration through a layer of mucus overlying a monolayer of cultured intestinal epithelial cells from the T84 cell line. Neutrophils migrated rapidly through human midcycle cervical mucus: the random motility coefficient (mu) ranged from 1.2 to 5.6 x 10( 8) cm2/sec in different mucus samples. The rate and pattern of neutrophil migration in cervical mucus were identical to those in a structurally similar collagen gel (0.4 mg/ml). Therefore, we also quantitatively examined the migratory behavior of human neutrophils, monocytes, and lymphocytes from peripheral blood, as well as leukocytes isolated from semen, in collagen gels as a model of cell migration in cervical mucus. In the absence of stimulation, mu was approximately 10(-8) cm2/s for neutrophils and lymphocytes; monocytes and seminal leukocytes were immotile. In all cases, mu increased with the addition of FMLP. Furthermore, neutrophils were able to penetrate layers of mucus overlying monolayers of T84 cells when the gel thickness was less than approximately 500 microns. These results suggest that leukocytes migrate effectively through mucus, a process which may be related to their ability to function in the mucosal immune system or to serve as vectors for the translocation of infectious pathogens like HIV. PMID- 8200045 TI - Regulation of chemokine production by the oxidative metabolism of L-arginine in a human mixed lymphocyte reaction. AB - Previous studies have shown that during the development of a mixed lymphocyte reaction (MLR) levels of the chemotactic cytokines IL-8 and MCP-1 (members of the C-X-C and C-C supergene families, respectively) increase in a time-dependent fashion, and that the production of these chemokines correlates with the magnitude of responsiveness to alloantigen. Furthermore, the responsiveness to alloantigen in the context of a MLR has been shown to be regulated by the oxidative metabolism of L-arginine. We postulated that competitive antagonism of the L-arginine metabolic pathway in a human MLR may alter the production of members of the C-C and C-X-C chemokine families. To test this hypothesis, mononuclear cells were isolated from healthy individuals and subjected to a one way MLR in the presence or absence of varying concentrations of an L-arginine competitive inhibitor, NG-methyl-L-arginine (NMA: 50 to 500 microM). When the MLR was performed in the presence of NMA (500 microM), the production of IL-8 increased twofold (P < 0.05) and ENA-78 increased fivefold (P < 0.05), while MCP 1 and MIP-1 alpha were not significantly altered. These findings suggest that NMA, an inhibitor of the L-arginine metabolic pathway, may regulate the production of specific C-X-C chemokines, IL-8 and ENA-78, during a MLR. In contrast, the production of MCP-1 and MIP-1 alpha, members of the C-C chemokine family, does not appear to be regulated by this inhibitor of the oxidative metabolism of L-arginine in the context of a MLR. PMID- 8200047 TI - [An operating chair for microsurgery of the eye]. PMID- 8200046 TI - [Therapy of malignant melanoma of the uvea]. AB - The author gives an account of different therapeutic possibilities as regards treatment of malignant melanomas of the uvea. She describes factors which influence the selection of therapy and indications of different methods. PMID- 8200048 TI - [A portable stand for microsurgical instruments]. PMID- 8200049 TI - [The International Eye Bank of Prague--its second year of activity]. AB - The job and results of International Eye Bank of Prague in 1993 are described. The experience from the work of Eye Bank and some results of statistical processing of basic information about donors and recipients are presented. The necessity of close cooperation between Eye Bank and ophthalmological clinics and particularly between Eye Bank and various units from hospitals cooperating in the search for suitable donors is stressed in conclusion. PMID- 8200050 TI - [Results of treatment of malignant melanoma of the choroid using local beta irradiation (Ru106/Rh106) from 1988 to 1992]. AB - In the work results of focused, local therapy of the MMU (localised at choroidea) in the years 1988-92, with episclerally fixed applicators of the beta-emittors Ru106/Rh106 are presented. After this, so called "brachytherapy" (without enucleation), the group of 17 eyes (treated 18 times) was evaluated 18-54 months after therapy. Favourable results of treatment of the MMU at choroidea (small and localised) with episcleral, focused beta-radiation are emphasised. Up to December 31, 1992 at the group of 17 eyes healed MMU of the choroidea showed 58.8% of treated patients. Effective visual acuity (between 0.4-1.0) was preserved in 66.6% of the eyes. Exitus due to metastases occurred in 5 patients (24-48 month after therapy) showing the mortality rate 29.4%. These results are comparable with published statistics. PMID- 8200051 TI - [Intraocular malignant melanoma in intermediate uveitis treated conservatively and surgically for a prolonged period]. AB - The authors give an account of a 28-year-old female patient treated for a prolonged period in the out-patient department on account of intermediary uveitis with subsequent pars plana vitrectomy of the left eye. After repeatedly deteriorating local findings after a 4-month interval in the punctate of the anterior chamber cells of non-differentiated malignant melanoma were detected; histological examination of the enucleated bulbus confirmed the diagnosis of malignant melanoma penetrating into the optic nerve. PMID- 8200052 TI - [Exenteration of the orbit]. AB - The authors evaluate the number and results of exenterations of the orbit on account of malignant neoplasms originating in intraocular structures and penetrating into the orbit or malignant processes originating in structures of the orbital contents and tissues surrounding the orbit. These operations were made in a group of 156 patients with orbital disease hospitalized at the First Ophthalmological Clinic, Faculty Hospital and Medical Faculty, Comenius University, Bratislava in 1980-1992. During the mentioned 13-year period exenteration of the orbit was indicated in 22 patients, i.e. 14.1% from the total number of 156 hospitalized patients with orbital disease. PMID- 8200053 TI - [Diseases of the orbit]. AB - In the submitted paper the authors analyze data from a group of patients with diseases of the orbit treated at the First Ophthalmological Clinic, Faculty Hospital, Medical Faculty Comenius University Bratislava between the beginning of 1980 and the end of 1992. During the mentioned period 156 patients with orbital diseases were hospitalized or put on record. The 13-year group of patients is evaluated from the aspect of causes of exophthalmos, age distribution, lateralization of the disease and different diseases by sex. Special attention is paid to a sub-group of 70 patients with tumours of the orbit. PMID- 8200055 TI - Interaction of tocopherol with peroxyl radicals does not lead to the formation of lipid hydroperoxides in liposomes. AB - alpha-Tocopherol (alpha-TOH) is thought to act as a lipid-soluble antioxidant by scavenging the chain-carrying lipid peroxyl radical (LOO.), giving rise to alpha TO. and LOOH. The aim of the present work is to test the possibility that alpha TOH may also exert a protective action by converting LOO. into the parent, unoxidized lipid molecule (LH) with concomitant formation of O2- and T+O. To assess the relative contribution of the two pathways, the amounts of products accumulating were measured, i.e. LOOH and O2-, under conditions where lipid peroxidation was initiated at linear rates by the UV light-induced decomposition of AIBN. The overall conclusion of the study is based on the observation that significant amounts of O2- were produced, whereas the delta LOOH/delta alpha-TOH was considerably smaller than 1.0. A mechanism of one or two-electron oxidation of TOH is considered; according to it the phospholipid primary structure is restored (LOO.-->LH, breaking of the C-->O bond). This leads to the oxygen or superoxide anion-radical release accordingly. PMID- 8200054 TI - Phases and phase transitions of the hydrated phosphatidylethanolamines. AB - LIPIDAT is a computerized database providing access to the wealth of information scattered throughout the literature concerning synthetic and biologically derived polar lipid polymorphic and mesomorphic phase behavior. Here, a review of the LIPIDAT data subset referring to hydrated phosphatidylethanolamines (PE) is presented together with an analysis of these data. The PE subset represents 14% of all LIPIDAT records. It includes data collected over a 38-year period and consists of 1511 records obtained from 203 articles in 35 different journals. An analysis of the data in the subset has allowed us to identify trends in synthetic PE phase behavior reflecting changes in lipid chain length, chain unsaturation (number, isomeric type and position of double bonds), chain asymmetry and branching, type of chain-glycerol linkage (ether vs. ester) and headgroup modification. Also included is a summary of the data concerning the effect of pH, stereochemical purity, and different additives such as salts, saccharides, alcohols, amino adds and alkanes on PE phase behavior. Information on the phase behavior of biologically derived PE is also presented. This review includes 236 references. PMID- 8200056 TI - Fluorescence microscopy study of Langmuir monolayers of racemic and enantiomeric N-stearoyltyrosine. AB - Monolayers of N-stearoyltyrosine have been investigated by fluorescence microscopy and surface pressure measurements. The racemic films are more condensed than the enantiomeric films, indicating heterochiral discrimination. The surface pressure at the transition to the condensed phase on compression decreases monotonically between XD = 0 and XD = 0.5 at 33 degrees C. The condensed-phase domains of the monolayer of the pure L enantiomer appear as anisotropic shapes under a fluorescence microscope. The condensed-phase domains of the racemic monolayer appear more compact at lower temperatures, but their morphology becomes progressively more anisotropic as the temperature increases. The difference between the surface pressure isotherm of the enantiomeric L and the racemic film are smaller and homochiral for the N-stearoyltyrosine methyl ester on a pH 7 buffered subphase than for the N-stearoyltyrosine on a pH 2 HCl acidified subphase at 22 degrees C, indicating the importance of hydrogen bonding in accounting for the origin of the chiral discrimination. PMID- 8200057 TI - Self-assembled microstructures from 1,2-ethanediol suspensions of pure and binary mixtures of neutral and acidic biological galactosylceramides. AB - Optical and electron microscopy were employed to characterize microstructures formed by thermal mechanical treatment of glycol suspensions of various pure and binary mixtures of the brain-derived galactosphingolipids hydroxy fatty acid cerebroside (HFA-Cer), non-hydroxy fatty acid cerebroside (NFA-Cer) and sulfatide (S-Cer). Negative staining indicated some new features of the neutral cerebroside suspensions in glycol. HFA-Cer formed a small fraction of both unilamellar cylinders (ULCs) (lumina ca. 27 nm) and giant multilamellar cochleates in addition to the typical nonhelical multilamellar cylinders (MLCs) (lumina ca. 10 30 nm). NFA-Cer formed a gel composed of a significant fraction of very long ULCs (lumina ca. 17 nm) without helical substructure, in addition to multilamellar helical structures such as ribbons and cylinders (lumina ca. 70 nm). Anisotropic lamellar micelle-shards of NFA-Cer were also detected by negative staining. S-Cer formed short ULCs (lumina ca. 44 nm) with no obvious helical substructure. Complex mixture data are thought to result from thermodynamic and kinetic factors. HFA-Cer is highly insoluble and promotes a network of rigid intralamellar hydrogen bonding that tends to exclude other lipids. NFA-Cer stabilizes helical defects in the lamellae, and S-Cer enhances disorder or micellization. The processes of microstructure nucleation and lipid phase separation were affected by mixtures such that metastable microstructures were trapped or the length of lamellar cylinders was altered. PMID- 8200058 TI - Fluorescence study of a derivatized diacylglycerol incorporated in model membranes. AB - A fluorescence study of a diacylglycerol derivatized with the n-(7-nitrobenz-2 oxa-1,3-diazol-4-yl) chromophore (NBD) was carried out. Fluorescence self quenching was observed for this probe in lecithin model membranes due to collisional interaction rather than to an aggregational behaviour of the probe. The efficient energy migration (Ro = 28 A) of the NBD fluorophore was studied via the fluorescence depolarization upon increase of probe concentration in membranes, and the results are compared with a model where a random distribution of the probes is assumed. A surface location of the chromophore was concluded for the NBD derivative of diacylglycerol, both from the fluorescence parameters and from the study of its fluorescence quenching by spin label probes. Very high lateral diffusion coefficients were obtained for these probes, both from the self quenching (D = 2-6 x 10(-6) cm2 s-1) and from the spin probe quenching (D = 3.5 x 10(-6) cm2 s-1) studies. A concomitant fluorescence study of the related probe NBD-phosphatidylcholine revealed that its photophysical behaviour is similar to the derivatized diacylglycerol. PMID- 8200059 TI - Autoxidation and antioxidant activity of ubiquinol homologues in large unilamellar vesicles. AB - The antioxidant activity of ubiquinol homologues with different side-chain length such as ubiquinol-3 and ubiquinol-7 was compared with that of alpha-tocopherol when peroxidation was induced by the water-soluble initiator 2,2'-azobis-(2 amidinopropane hydrochloride). In large unilamellar vesicles containing equal amounts of alpha-tocopherol, ubiquinol-3 and ubiquinol-7 the rates of inhibition were very similar but the stoichiometric factor of quinols was approximately 1. To explain this low value, which is one-half of that found when the autoxidation was performed in apolar solvents (Chem. Phys. Lipids (1992) 61, 121-130), the oxidation of alpha-tocopherol and ubiquinol-3 initiated by the azocompound was studied both in methanol and in dimiristoyl-lecithin vesicles. The results obtained show that the ubiquinol homologues undergo a radical chain reaction taking place at the polar interface and suggest that the average preferred location of both quinol headgroups is near to the outer surface of the bilayer. PMID- 8200060 TI - Differential transformation efficiency but not AP-1 induction under anchorage dependent and -independent conditions. AB - The JB6 mouse epidermal cell system has been extensively used as an in vitro model for the study of tumor promotion. The present study aimed to assess the relevance of monolayer measurements to the process of transformation, which is induced more efficiently under anchorage-independent (AI) conditions. Although it would be ideal to use identical conditions for studying tumor promoter-induced transformation and biochemical and molecular events that may cause the process, it is not feasible in the case of soft agar conditions because cells cannot be readily recovered. In the present report, we used liquid medium over agar as an AI condition that permitted efficient recovery of cells. Responses to tumor promoter have been compared with those in monolayer and semisolid agar. Results indicate that 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced similar magnitude concentration-dependent transformation of JB6 cells under both of the AI conditions, namely soft agar and over-agar. Under anchorage-dependent (AD) conditions of exposure to TPA, the transformation efficiency was much lower than that seen under AI conditions. Mechanical detachment of monolayer cells after 5 10 days TPA exposure enriched the transformed phenotype. Activator protein 1 transcriptional activity measured at 12 h was induced equally under AD and AI conditions, and thus is not an early limiting event that could explain the lower transformation efficiency seen under AD conditions. To summarize, the over-agar and monolayer assays described in this study can be considered valid for the study of early biochemical and molecular events relevant to the promotion of transformation measured in soft agar. PMID- 8200062 TI - The stimulatory effect of nickel chloride on DNA replication in human HeLa cells and Escherichia coli. AB - An investigation was undertaken to study DNA replication in cultured human HeLa cells and Escherichia coli in response to nickel chloride (NiCl2). Treatment with NiCl2 increased both the rate of DNA replication and total cell number in HeLa cells and E. coli in a time- and concentration-dependent manner. The maximum stimulation of thymidine uptake into DNA was observed with 0.125-0.25 mM NiCl2 for both cell types. In studies of DNA replication using a crude HeLa cellular extract, NiCl2 at concentrations below 0.125 mM also induced a stimulation over the background of MgCl2-dependent [3H]dTMP incorporation into activated calf thymus DNA. However, a similar stimulatory effect from NiCl2 was not observed with either purified HeLa DNA polymerase alpha or E.coli DNA polymerase I Klenow fragment. In the absence of Mg2+, the low response of either DNA polymerase alpha or Klenow fragment to stimulation by Ni2+ was thought to be enhanced by the presence of Ni(2+)-binding proteins presented in the crude HeLa cell extract. PMID- 8200061 TI - Overexpression of c-K-ras, c-N-ras and transforming growth factor beta co segregate with tumorigenicity in morphologically transformed C3H 10T1/2 cell lines. AB - Morphologic transformation and tumorigenicity are separate cellular phenotypes in transformed 10T1/2 cells. We have investigated the levels of expression of genes for c-myc, c-H-ras, c-K-ras, c-N-ras, TGF beta and Rb in 42 morphologically transformed 10T1/2 cell lines, in an attempt to define the molecular mechanisms governing morphologic transformation and tumorigenicity in the 10T1/2 cell system. The 10T1/2 cell lines investigated generally overexpressed mRNAs for c myc, c-H-ras, and TGF beta relative to the levels expressed by wild-type 10T1/2 cells (levels of expression > 1.5-fold that of wild-type 10T1/2 cells). In contrast, only half of these cell lines overexpressed mRNAs for c-N-ras and/or Rb relative to wild-type 10T1/2 cells, and only 25% overexpressed c-K-ras mRNA. The mean levels of mRNA expression for each of c-K-ras, c-N-ras and TGF beta genes in tumorigenic cell lines were significantly greater than the mean levels of expression in non-tumorigenic cell lines, suggesting an association between tumorigenicity and the levels of expression of these specific genes. In contrast, levels of expression for c-myc, c-H-ras and Rb genes were not correlated with tumorigenicity. Cell lines that coexpressed high levels of c-K-ras, c-N-ras and TGF beta genes were likely to be tumorigenic (11/12 cell lines were tumorigenic), whereas cell lines that coexpressed low levels of these genes were unlikely to be tumorigenic (1/10 cell lines were tumorigenic). High expression of TGF beta was sufficient for tumorigenicity in the absence of high levels of expression of c-K ras and c-N-ras (5/5 cell lines were tumorigenic). Elevated expression of either c-K-ras or c-N-ras alone was insufficient for tumorigenicity, however, coordinate overexpression of both c-K-ras and c-N-ras was associated with tumorigenicity irrespective of the expression status for TGF beta (13/15 cell lines were tumorigenic). These results suggest that overexpression of c-myc, c-H-ras and TGF beta are commonly associated with, and possibly mechanistically related to, the process of morphologic transformation in 10T1/2 cells. In addition, these results suggest that progression from morphologic transformation to tumorigenicity in 10T1/2 cell lines is frequently accompanied by overexpression of c-K-ras and c-N ras, and by enhancement of the level of overexpression of TGF beta. PMID- 8200063 TI - Granulocyte-macrophage colony stimulating factor gene expression and function during tumor promotion. AB - Although recent evidence suggests that granulocyte-macrophage colony stimulating factor (GM-CSF) plays a role in cutaneous inflammation induced by topical exposure of phorbol ester tumor promoters to murine epidermis, there is little information available on the temporal sequence of gene expression of this cytokine over the time course of tumor promotion or about its function in this process. The goal of the present studies was to examine the potential role of GM CSF in tumor promotion in SENCAR mice. Competitive reverse transcriptase polymerase chain reaction (RT-PCR) studies demonstrated that a single topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA; 2 micrograms, 10 micrograms) to the dorsal epidermis of SENCAR mouse skin stimulated a dose and time dependent GM-CSF gene expression that was upregulated at 1 h after TPA exposure, peaked at 3 h and declined at 12 h. Although treatment with 7',12' dimethylbenz[a]anthracene (DMBA) did not stimulate GM-CSF gene expression, GM-CSF gene expression was elevated in epidermal tissue isolated from SENCAR mice treated with a single application of 10 nmol DMBA followed by multiple applications of 2 micrograms TPA over a 1-22 week time course. Immunochemical and autoradiographic studies demonstrated that GM-CSF protein was produced by suprabasal keratinocytes, interfollicular cells, nonproliferating papilloma cells and leukocytes within the dermis. Intraperitoneal injection of recombinant (r) GM CSF into SENCAR mice at 2 h prior to topical application of 10 micrograms TPA induced a significant increase in epidermal keratinocyte proliferation, leukocyte infiltration into the dermis, hydroperoxide production by circulating neutrophils and chemotactic activity present within the plasma at 24 h compared to treatment with only 10 micrograms TPA. Intravenous injection of anti-GM-CSF antibodies significantly inhibited both local and systemic inflammatory events induced by topical application of TPA. The present studies suggest that GM-CSF has a broad spectrum of activity with at least two target cell populations, epidermal keratinocytes within the proliferative compartment and leukocytes. This cytokine is actively transcribed during the tumor promotion process, acts as a signal peptide that stimulates epidermal proliferation, primes circulating neutrophils to produce hydroperoxide and regulates leukocyte migration. PMID- 8200064 TI - Aldehyde-induced protein-DNA crosslinks disrupt specific stages of SV40 DNA replication. AB - Aldehydes with specific protein-DNA crosslinking ability disrupted simian virus 40 (SV40) DNA replication to cause replication fork failure by the 40S intermediate pathway, in which replicating viral genomes become inactivated and torsionally stressed. In contrast, aldehydes without detectable protein-DNA crosslinking ability had no effect on SV40 DNA replication during the 10 min exposure times employed. This indicates that protein-DNA crosslinks block either DNA polymerase or the entire replication complex. Replication failure by the 40S pathway is known to initiate recombinational events in the damaged SV40 replicons. Similar events in cellular replicons may play a role in the clastogenic effects of formaldehyde. In addition, formaldehyde and acrolein caused accumulation of catenated (topologically linked) SV40 daughter chromosomes -a signature of topoisomerase II inhibition. PMID- 8200065 TI - Synergistic enhancement of hepatic foci development by combined treatment of rats with 10 heterocyclic amines at low doses. AB - Potential synergism between 10 carcinogenic heterocyclic amines [3-amino-1,4 dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3 b]indole (Trp-P-2), 2-amino-6 methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 2 amino-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), 2-amino-3-methylimidazo[4,5 f]quinoline (IQ), 2-amino-3,4-dimethyl-imidazo[4,5-f]quinoline (MeIQ), 2-amino 3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methyl-9H-pyrido[2,3 b]indole (MeA alpha C), 2-amino-9H-pyrido[2,3-b]indole (A alpha C) and 2-amino-1 methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)] in rat liver carcinogenesis was examined. Male F344 rats were initially given diethylnitrosamine (200 mg/kg, i.p.) and beginning 2 weeks later received heterocyclic amines individually at doses 1/10 of that proven to be carcinogenic or in combination at 1/10 or 1/100 doses for 6 weeks. All animals were subjected to partial hepatectomy at week 3 and killed at week 8. The induction of immunohistochemically demonstrable placental glutathione S-transferase positive foci was significantly increased in rats given all 10 chemicals in combination at the 1/10 dose level while values were almost the same as in controls with the 1/100 dose mixture and the individual chemicals, except for Glu-P-1 which significantly increased foci development and Glu-P-2 and A alpha c which significantly decreased levels of foci at the 1/10 dose level. Thus apparent synergism was observed with the 1/10 dose level combination. When the data are considered together with our previous results obtained with five heterocyclic amines using 1/1, 1/5 and 1/25 dose levels, combined effects were found to be related to the number of chemicals included and the dose levels of each, with a possible isoadditive influence being common. The findings are of particular significance since heterocyclic amines and other carcinogenic agents might be simultaneously generated during cooking. PMID- 8200066 TI - Retinoic acid and beta-carotene inhibit fibronectin synthesis and release by fibroblasts; antagonism to phorbol ester. AB - Previous work from our and other laboratories has shown that tumor promoters stimulated the loss of fibronectin (FN) from the cell surface of fibroblasts in culture; retinoic acid (RA) appeared to counteract this loss. We have now studied the action of RA and carotenoids on FN synthesis and release. Using mouse fibroblasts (C3H/10T1/2 cells), we found that RA inhibited release of FN into the medium in a time- and concentration-dependent manner (e.g. 90% inhibition in 48 h with 1 x 10(-6) M RA). RA caused inhibition of synthesis, as well as a time- and concentration-dependent decrease in FN mRNA. A second phenomenon we observed was the greatly increased binding of FN to the surface of the cells, both in dimeric and multimeric forms, caused by RA treatment. RA produced a striking inhibition of the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-stimulated FN release from the cell surface usually associated with tumor promotion. We postulate that the combined action of RA in causing decreased FN synthesis and increased FN binding to the cell surface is the reason for the apparent antagonism of RA to the TPA stimulated release of FN. Surprisingly, beta-carotene (BC) and canthaxanthin (a non-provitamin A carotenoid) also inhibited the release of FN from these cells. The action of BC was specific, in that an antioxidant carotenoid (trans-methyl bixin) and lycopene were inactive. BC also inhibited FN synthesis and thus inhibited the TPA-stimulated release of FN, similar to RA, but to a lesser extent. BC had no effect on the binding of FN to the cell surface. PMID- 8200067 TI - Use of azoxymethane-induced foci of aberrant crypts in rat colon to identify potential cancer chemopreventive agents. AB - Foci of aberrant and/or hexosaminidase-negative crypts in rat colon are putative precancerous lesions that have been proposed as biomarkers for short-term bioassays for chemical carcinogens and chemopreventive agents. The ability of a substance to reduce the yield of azoxymethane (AOM)-induced foci in the colon of male Fischer 344 rats, was evaluated as a screening assay for chemopreventive agents. Twenty-eight test agents were administered continuously in the diet from the start of the experiments until the animals were killed 35 days later. AOM was s.c. administered either as 15 mg/kg body wt on days 7 and 14 or as 30 mg/kg body wt on day 7 of the experiment. Foci of aberrant crypts were evaluated in whole mounts of methylene blue-stained colons. AOM induced twice as many foci when administered between 8.40 and 11.00 a.m. than between 2.45 and 5.55 p.m. Calcium salts of carbonate, chloride and glucarate decreased the yield of AOM-induced foci while the acidic salts of lactate and phosphate did not inhibit the formation of foci. Dimethyl-fumarate, fumaric acid, genistein, piroxicam, simethicone, sodium suramin and sulindac reduced the yield of AOM-induced foci of aberrant crypts, with genistein being the most potent. Only piroxicam of this group has previously been shown to inhibit colon cancer, while the rest have yet to be evaluated. Ibuprofen did not inhibit the formation of foci, although it has been reported to inhibit AOM-induced colon cancer in rats. Piroxicam and sulindac appeared to reduce preferentially hexosaminidase-negative foci of aberrant crypts, compared with those of apparently normal morphology. The AOM-induced foci of aberrant crypts assay appears suitable for screening chemicals for chemopreventive action. PMID- 8200068 TI - Inhibitory effect of beta-carotene on chronic 2-acetylaminofluorene induced hepatocarcinogenesis in rat: reflection in hepatic drug metabolism. AB - The dietary administration of beta-carotene (BC; 100 mg/kg food) daily has been found to be highly effective in reducing cancer incidence in male Sprague-Dawley rats fed 2-acetyl-aminofluorene (0.05% in food). BC treatment either before initiation, during initiation and selection/promotion phases of hepatocarcinogenesis have been found to be effective in elevating hepatic microsomal cytochrome b5 (24-50%), P-450 (18-38.5%), NADPH cytochrome c reductase (17.5-43.25%) and cytosolic aryl hydrocarbon hydroxylase (60.5-63.5%) activity to a statistically significant level measured either in the hyperplastic nodule (HN) or in the non nodular surrounding liver parenchyma (NNSP) compared to carcinogen control. Moreover, BC treatment throughout the study decrease the cytosolic 1 chloro-2,4-dinitrobenzene conjugated glutathione S-transferase (38.9-51.22%) and microsomal UDP-glucuronyl transferase (37.3-59.1%) activities to a significant level when compared to carcinogen control rats. A decrease in the number of hyperplastic nodules and their total liver parenchyma occupied were also observed in BC treated groups. Furthermore, a direct correlation between HNs and NNSP liver areas were observed with the hepatic BC and vitamin A contents and also with the rates and patterns of hepatic drug metabolism. Our results confirm the fact that BC is particularly protective in limiting the action of 2-AAF during the initiation phase of hepatocarcinogenesis. PMID- 8200069 TI - Nicotine inhibits the metabolic activation of the tobacco-specific nitrosamine 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats. AB - The effect of nicotine on the metabolism of the tobacco-specific nitrosamine 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was studied in rats. [1 14C]NNK was s.c. injected at a dose of 0.08 mumol/kg. Co-administration of a 500 fold higher dose of nicotine (40 mumol/kg) did not reduce the overall urinary excretion of radioactivity. However, the metabolic pattern in 24 h urine was significantly changed. Metabolites resulting from NNK activation by alpha hydroxylation were significantly (P < 0.001) reduced to 72% of the control. Detoxification to N-oxides and the glucuronide of 4-(methyl-nitrosamino)-1-(3 pyridyl)-1-butanol increased to 155% (P < 0.01) and 188% (P < 0.01) of the control respectively. These results suggest that nicotine, which occurs in concentrations up to 30,000-fold higher than NNK in mainstream smoke of cigarettes may have a protective effect against metabolic activation of NNK. PMID- 8200070 TI - DNA adducts of the ubiquitous environmental contaminant cyclopenta[cd]pyrene. AB - The bioactivation of cyclopenta[cd]pyrene (CPP) was investigated to determine the major DNA adduct-forming metabolite(s) of this widespread environmental contaminant and suspect carcinogen. DNA adducts were analyzed by 32P postlabeling. Four major and at least seven minor adducts formed when CPP was incubated with calf thymus DNA in the presence of rat liver microsomal systems. P450 subfamilies IA and IIB both activated CPP as microsomes from either phenobarbital- or beta-naphthoflavone-treated rats produced quantitatively similar and qualitatively identical adducts. When the epoxide hydrolase inhibitors, 1,1,1-trichloropropene-2,3-oxide or cyclohexene oxide were added to the incubations, binding increased 2.5- to 4-fold, suggesting epoxidation as a mechanism of adduct formation in vitro. Sprague-Dawley rats were killed 1, 3, 7, 18, 45 and 80 days postdosing i.p. with 50 mg/kg CPP. In all tissues analyzed, four major and several minor qualitatively identical adducts were produced. Binding was highest and most persistent in lung followed by heart, white blood cells (WBCs) and liver. CPP adducts were detectable at doses from 1 microgram/kg to 50 mg/kg. Rat lung DNA adducts were cochromatographed with standardized deoxyguanosine and deoxyadenosine adducts produced by reaction of CPP-3,4-epoxide in vitro. All rat lung adducts comigrated with the deoxyguanosine adducts but one was clearly deoxyadenosine derived. Mouse skin DNA adducts from NIH Swiss mice and mouse lung DNA adducts from B6C3F1 mice were also analyzed. All adducts from either mouse tissue comigrated with rat lung DNA adducts, suggesting CPP-3,4 epoxide was also the major DNA adduct-forming species in the mouse. CPP-3,4 epoxide has been suggested to be the key mediator of the biological activities of CPP. Evidence presented here strongly suggests CPP-3,4-epoxide as the major adduct-forming species of CPP as catalyzed in vitro by rat liver preparations known to mediate the mutagenic activation of CPP, in the rat in vivo, and in mouse skin and lung, two tissues with known sensitivity to CPP tumorigenicity. PMID- 8200071 TI - Consumption of Brussels sprouts results in elevated alpha-class glutathione S transferase levels in human blood plasma. AB - The effect of consumption of glucosinolate-containing Brussels sprouts on alpha class glutathione S-transferase levels in human blood plasma was investigated in 10 healthy, male, non-smoking volunteers. Following a 3-week run-in period, five volunteers continued on a glucosinolate-free diet during a subsequent 3-week intervention period (control group), while the other five (sprouts group) consumed 300 g of cooked Brussels sprouts per day, at the expense of 300 g of a glucosinolate-free vegetable. alpha-Class glutathione S-transferases were measured by radioimmunoassay. In the control group, similar alpha-class glutathione S-transferase levels were observed in both periods (P = 0.814), while in the sprouts group the alpha-class glutathione S-transferase levels were elevated by a factor of 1.4 (P = 0.002). We hypothesize that the elevated alpha class GST levels in plasma reflect GST-alpha induction in tissues such as liver and small intestine under non-toxic conditions. The present findings indicate that alpha-class GST levels in plasma may be used as a biomarker for alpha-class GST levels in tissues. In addition, they support the results of epidemiologic studies that consumption of cruciferous vegetables may result in a decreased cancer risk. PMID- 8200072 TI - Ethnic distribution of the glutathione transferase Mu 1-1 (GSTM1) null genotype in 1473 individuals and application to bladder cancer susceptibility. AB - Polycyclic aromatic hydrocarbons, found in cigarette smoke, food and industrial materials, are potential human carcinogens. Deficiency of detoxifying enzymes, such as glutathione transferases, may affect the metabolic fates of these chemicals and raise cancer risks in exposed individuals. The GSTM1 null genotype is a common form of glutathione transferase deficiency. Because knowledge of its ethnic distribution would be useful in epidemiologic studies, we measured the frequencies of the GSTM1 null genotype among healthy blacks, whites, Asian Indians, Chinese, Japanese, Koreans, Filipinos, Samoans and Hispanics. Rapid genotyping was done by use of a PCR assay, with dried blood spots on blotter paper as DNA templates. The frequency of the null genotype ranged from 0.31 among blacks to 0.88 among Samoans. The PCR assay was also applied to a pilot study of 114 bladder cancer cases from Kaiser Permanente Medical Center, Harbor City, California. DNA for these cases was obtained from paraffin-embedded surgical specimens. The overall odds ratio for bladder cancer with the GSTM1 null genotype was 1.4 (95% confidence interval 0.94-2.1), indicating no statistical difference in null genotype frequencies among bladder cancer patients compared to a healthy population. Large epidemiologic studies, which can be accomplished with dried blood spots or paraffin-embedded tissue specimens, may be useful for further assessment. PMID- 8200073 TI - Low frequency of H-ras mutations in hepatocellular adenomas and carcinomas and in hepatoblastomas from B6C3F1 mice exposed to oxazepam in the diet. AB - Oxazepam has been the subject of recent toxicological and carcinogenesis studies because it is a commonly prescribed tranquilizer and has been shown to cause tumors in rodents. In this study, male and female B6C3F1 mice received 0, 125, 2500 or 5000 p.p.m. oxazepam in the diet for up to 2 years. Hepatocellular adenomas and carcinomas, as well as hepatoblastomas, which developed in these mice, were examined for the presence of activated ras proto-oncogenes. DNA was isolated from 20 or more tumors from each exposure group and analyzed by oligonucleotide hybridization, single-stranded conformation polymorphism analysis and direct sequencing of PCR-amplified H-ras gene fragments for codon 61 mutations. Thirteen of 37 (35%) hepatocellular adenomas and carcinomas from the 125 p.p.m. exposure group had mutations in codon 61, while mutations were detected in only 2 of 25 or 8% of the liver tumors from the 2500 p.p.m. exposure group and none of the 22 tumors from the 5000 p.p.m. group. This compares to 63% of 126 historical control liver tumors and 55% of 20 liver tumors from unexposed B6C3F1 mice in this study. In addition, 12 hepatoblastomas from the two high dose groups were examined for H-ras mutations at codon 61, but none were detected. No tumor DNAs from any of the exposure groups tested had mutations in codons 12, 13 or 117 of the H-ras gene or codons 12 or 13 of the K-ras gene, the other known hotspots for ras activation in mouse liver tumors. These results, together with those from the National Toxicology Program study showing no evidence of cytotoxicity or genotoxicity by oxazepam, suggest that oxazepam preferentially promotes cells that have activating lesions other than ras. PMID- 8200074 TI - The genotoxic carcinogen chromium(VI) alters the metal-inducible expression but not the basal expression of the metallothionein gene in vivo. AB - The ability of the carcinogen chromium(VI) to affect the basal and zinc-inducible expression of liver metallothionein was examined in 14- and 18-day chicken embryos in vivo. Metallothionein expression varied with the stage of embryo development, with basal steady-state mRNA levels being approximately three times lower in livers of 18-day versus 14-day chicken embryos. Chromium(VI) treatment had no effect on the basal steady-state levels of metallothionein mRNA and protein in either 14- or 18-day chicken embryo liver. Treatment of 14-day embryos with zinc(II) resulted in a 3- to 5-fold increase in steady-state levels of metallothionein mRNA in liver. Pre-treatment of 14-day embryos with chromium(VI) inhibited the zinc(II)-induced increase in steady-state levels of metallothionein mRNA and protein in liver by 30-50%. In contrast, chromium(VI) and/or zinc(II) treatments had no effect on steady-state levels of beta-actin mRNA. PMID- 8200075 TI - Inhibition of reporter gene expression in mammalian cells. Effects of distinct carcinogen lesions in DNA. AB - The effect of UV photoproducts or benzo[a]pyrene-diol-epoxide-I (BPDE-I) adducts in DNA on the transient expression of a reporter gene was measured in mammalian cells. The plasmid pRSVCAT was UV irradiated or treated with BPDE-I in vitro and co-transfected with undamaged pRSVBGAL into mouse and human fibroblasts. Variations in transfection efficiency among different cell lines were corrected by adjusting the volumes of cell extracts used in the chloramphenicol acetyl transferase (CAT) assays to contain equal beta-galactosidase (BGAL) activity. The expression of the CAT gene was found to decrease exponentially after transfection of pRSVCAT containing increasing numbers of DNA lesions per molecule. The average number of BPDE-I adducts per plasmid molecule was measured by ELISA; the average number of pyrimidine dimers was estimated from the dose kinetics for the disappearance of the supercoiled form of irradiated plasmid DNA treated with Micrococcus luteus UV endonuclease. By expressing the inhibition of CAT activity in terms of the average number of lesions per gene, we were able to compare directly the effects of two different carcinogen lesions on transient transcription. We observed comparable kinetics of inhibition of gene expression by BPDE-I adducts and pyrimidine dimers in DNA. D0 values determined by linear regression analysis of dose-response curves for inhibition of CAT activity were 4.9 BPDE-I adducts or 6.6 pyrimidine dimers per gene in excision-proficient human fibroblasts; the corresponding values in mouse cells were 4.4 BPDE-I adducts or 5.5 pyrimidine dimers. Similar threshold densities of BPDE-I adducts and pyrimidine dimers were observed before inhibition of transcription from pRSVCAT was detected. No threshold was observed in experiments with human fibroblasts deficient in excision repair (xeroderma pigmentosum group A); calculated D0 values were 1.2 pyrimidine dimers of 2.1 BPDE-I adducts. Our results permit direct comparisons of the magnitude of inhibition of gene transcription by distinct DNA lesions, and suggest that BPDE-I adducts and UV-induced cyclobutane pyrimidine dimers in template DNA block transcription with similar efficacy. PMID- 8200076 TI - The detection of adducts in human cervix tissue DNA using 32P-postlabelling: a study of the relationship with smoking history and oral contraceptive use. AB - 32P-Postlabelling was used to measure DNA adducts in the human cervix. Adduct levels were compared with patient smoking histories and contraceptive use. DNA adducts were found in 43 out of 58 samples. The number of adducts ranged from 0.2 to 59.5 adducts/10(8) nucleotides, though no significant difference was found to exist between the number of DNA adducts detected and the smoking history of each patient. In contrast, a significant difference at the 1% probability level was found between the adduct levels obtained from the cervical DNA of smokers who had used oral contraceptives and smokers who did not. Autoradiograms revealed a variety of adduct patterns. Some were found to have a diagonal zone of radioactivity which migrated from the origin of the TLC plate. Other autoradiograms revealed the presence of additional adduct spots located in the upper regions of the TLC plate, whereas others revealed the presence of these adduct spots alone. The origin of the adduct spots located in the upper regions of the TLC plate is unknown. PMID- 8200077 TI - Co-chromatography of a tamoxifen epoxide-deoxyguanylic acid adduct with a major DNA adduct formed in the livers of tamoxifen-treated rats. AB - Tamoxifen is a potent liver carcinogen in rats and has been shown to form covalent DNA adducts in the livers of several species of rodent. We have shown previously by 32P-postlabeling (Carcinogenesis, 13, 2197-2203) that > 85% of the total adducts detected and resolved by multi-directional TLC migrate as a single spot. In the present study, this material was further analysed by reverse-phase HPLC and resolved into two approximately equal components. Tamoxifen 1,2-epoxide, a postulated metabolite of tamoxifen, was reacted with DNA and polydeoxyribonucleotides and the products analysed. 32P-Postlabeling revealed three major adduct spots on TLC which comigrated with the three major adduct spots seen with DNA from livers of tamoxifen-treated rats. Moreover, the major epoxide adduct, which contained guanine as the modified base, eluted on HPLC as a single major peak coincident with one of the major peaks derived from the liver DNA of tamoxifen-treated rats. These results demonstrate that approximately 40% of the tamoxifen-DNA adducts formed in vivo are chromatographically indistinguishable with the major product of the reaction of tamoxifen epoxide with guanine residues in DNA and provide important clues to the mechanism of activation of tamoxifen to a genotoxic carcinogen. PMID- 8200078 TI - Strong intensification of mouse hepatic tamoxifen DNA adduct formation by pretreatment with the sulfotransferase inhibitor and ubiquitous environmental pollutant pentachlorophenol. AB - Although negative in assays for mutagenicity, the clinically important antiestrogen tamoxifen induces hepatic DNA adduct formation in mice, rats and hamsters, as indicated by 32P-postlabeling, and is a potent hepatocarcinogen in rats. Both phenolic and alcoholic metabolites of tamoxifen have been reported. As these metabolites are potential candidates for sulfate conjugation, we examined whether the sulfotransferase inhibitor pentachlorophenol, a ubiquitous environmental contaminant, modulates hepatic tamoxifen adduct formation in vivo. Female ICR mice were given tamoxifen (45 mg/kg) daily per os for up to 4 days, with and without i.p. pretreatment with pentachlorophenol (20 mg/kg) 1 h before dosing with tamoxifen. At days 1, 2 and 4, liver DNA was analyzed 5 h after tamoxifen administration by a modified monophosphate version of the 32P postlabeling assay. At day 4, pentachlorophenol pretreatment led to a large increase (13- to 17-fold) of the levels of four tamoxifen adduct fractions, while two adducts appeared unaffected, resulting in an approximately 7-fold enhancement of overall adduct formation. Significant pentachlorophenol related increases were also observed at day 1 and day 2. The mechanism of this effect has not yet been determined, but may involve the inhibition of sulfation of a tamoxifen metabolite(s) involved in the detoxication of the drug to nonelectrophilic derivatives. It was also apparent that there are two pathways of metabolic activation of tamoxifen, one being sensitive and the other resistant to pentachlorophenol. PMID- 8200079 TI - Inhibition of two-stage skin carcinogenesis as well as complete skin carcinogenesis by oral administration of TMK688, a potent lipoxygenase inhibitor. AB - 1-([5'-(3''-methoxy-4''-ethoxycarbonyloxyphenyl)-2',4'- pentadienoyl]aminoethyl) 4-diphenylmethoxypiperidine (TMK688) is a potent and orally active 5-lipoxygenase inhibitor having anti-histamine activity in its moiety. Recently, we have found that TMK688 also inhibits epidermal cyclooxygenase activity with a potency similar to its inhibiting 5-lipoxygenase. Oral administration of 30 mg/kg TMK688, a dose which markedly inhibits tumor promoter 12-O-tetradecanoylphorbol-13 acetate (TPA)-stimulated LTB4 formation in mouse skin, markedly inhibited both TPA-promoted and a non-TPA-type tumor promoter anthralin-promoted skin tumor formation in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated CD-1 mice. The inhibitory effect of TMK688 was not due to any damage inflicted on the initiated cells but due to its antitumor-promoting activity. TMK688 not only inhibited two stage skin carcinogenesis but also inhibited benzo[a]pyrene-caused complete skin carcinogenesis. Throughout the tumorigenesis experiment, the survival rate of animals was 100% and the TMK688-treated mice looked healthy. The body weight gain of TMK688-treated mice was not significantly different from that of non-treated mice. Both TMK688 and 1-([5'-(3''-methoxy-4''-hydroxyphenyl)-2',4' pentadienoyl]amino eth yl]-4-diphenylmethoxypiperidine (TMK777), an active metabolite of TMK688 having more potent 5-lipoxygenase inhibitory activity and less potent cyclooxygenase inhibitory activity than TMK688, inhibited epidermal 8 lipoxygenase activity induced by a topical application of TPA to mouse skin. The 8-lipoxygenase inhibitory activity of TMK777 was approximately 5 times more potent than that of TMK688. Indomethacin, a typical cylcloxygenase inhibitor, in topical doses which almost completely inhibit epidermal PGE2 formation, failed to inhibit or only slightly inhibited DMBA-initiated and TPA-promoted skin tumor formation. These results suggest that the cyclooxygenase inhibitory effect of TMK688 is not essential for its anti-tumor promoting activity. Although at present a possible contribution of anti-histamine activity cannot be ruled out completely, the anti-tumor promoting action of TMK688 may most probably be related to its anti-lipoxygenase activity. TMK688 seems to be a promising agent for the prevention of skin carcinogenesis. PMID- 8200080 TI - Modulation of urinary mutagenicity by genetically determined carcinogen metabolism in smokers. AB - We examined the genotypes of two polymorphic genes involved in the detoxification of several mutagenic and carcinogenic compounds in relation to tobacco smoking associated urinary mutagenicity. The genes studied were the glutathione S transferase-encoding GSTM1 gene and acetyltransferase-encoding NAT2 gene. Smokers with no GSTM1 gene (n = 7) had urine that was several times more mutagenic than that of smokers with the gene (n = 10). The mean level of urinary mutagenicity in presence of metabolic activation was 2527 +/- 958 revertants/100 ml urine for GSTM1-smokers compared to 766 +/- 560 revertants/100 ml for GSTM1+ smokers (P < 0.001) using the bacterial strain YG1024. The corresponding values using the TA98 strain were 336 +/- 124 and 123 +/- 75 (P < 0.001). In contrast, we failed to show any difference in the level of urinary mutagenicity between slow-acetylator and fast-acetylator NAT2 genotypes among smokers (n = 17) or non-smokers (n = 35). Our results offer one explanation for the recent findings that GSTM1 polymorphism is a risk modifier in smoking-related cancers, especially bladder cancer. PMID- 8200081 TI - Quinone methide mediates in vitro induction of ornithine decarboxylase by the tumor promoter butylated hydroxytoluene hydroperoxide. AB - Metabolism of the skin tumor promoter butylated hydroxy-toluene hydroperoxide (2,6-di-tert-butyl-4-hydroperoxyl-4-methyl-2,5-cyclohexadienone; BHTOOH) to reactive intermediates is required for tumor promotion by this compound. In particular, an electrophilic quinone methide is known to mediate both in vivo tumor promotion as well as in vitro cytotoxicity by BHTOOH. In the present study, the role of this reactive intermediate in the induction of ornithine decarboxylase (ODC), a gene strongly associated with tumor promotion, was investigated in cultured keratinocytes. BHTOOH stimulates a time-dependent increase in ODC enzyme activity, paralleled by ODC mRNA induction, suggesting transcriptional regulation of ODC by BHTOOH. Depletion of intracellular glutathione caused a 5-fold potentiation of keratinocyte sensitivity to BHTOOH. Concordantly, ODC induction by BHTOOH could be completely inhibited by soluble thiol compounds. These results suggest that ODC induction is mediated by a thiol reactive metabolite of BHTOOH. The iron-specific chelator desferal blocked ODC induction by BHTOOH, indicating that formation of this intermediate is iron dependent. Substitution of the 4-methyl group of BHTOOH with alkyl groups of incrementally larger size is known to reduce accordingly quinone methide production; comparative study of these BHTOOH analogs demonstrated a corresponding loss of potency for ODC induction, indicating that BHT-quinone methide mediates the in vitro induction of ODC by BHTOOH. Finally, kinase inhibitor studies suggested a role for protein kinase C in the induction of ODC by BHTOOH. Taken together, these results provide insight into the cellular mechanisms through which the reactive electrophile BHT-quinone methide can mediate alterations in gene expression, such as occur in tumor promotion in vivo. PMID- 8200082 TI - Different fates of camptothecin-induced replication fork-associated double-strand DNA breaks in mammalian cells. AB - The S phase cytotoxicity of camptothecin (CPT) requires both the formation of a covalent topoisomerase I-DNA complex and ongoing DNA replication. The interaction of DNA synthesis and the drug-induced complexes results in the production of DNA double-strand breaks (DSBs) concentrated in replicating DNA. These DSBs are likely to be extremely cytotoxic lesions and are likely to account for the S phase specificity of CPT. Here we show that a brief exposure to CPT results in replication-associated DSBs and, once formed, the fate of these DNA DSBs is different in human and Chinese hamster cell lines. In hamster CHO-KI, even at supra-lethal concentrations, CPT-induced DSBs in nascent DNA disappear within 5 h of drug removal. Those CHO-KI cells in S phase during treatment with toxic doses of CPT arrive at mitosis within 18 h, with potentially lethal chromatid aberrations. In human cells, CPT-induced DSBs are long lived, and are still detectable at least 24 h after drug removal. After toxic doses of CPT to S phase human cells, mitosis does not occur within 72 h of drug removal and there is an extended, perhaps permanent, cycle arrest in S/G2, possibly due to the presence of unrepaired DNA DSBs. These data, and the greater sensitivity of hamster than human cells to low doses of CPT, suggests that, besides the generation of replication fork-associated DNA DSBs, subsequent processing/repair of these lesions may modulate the sensitivity of cells to this important anti-tumour drug. PMID- 8200084 TI - High promutagen activating capacity of yeast microsomes containing human cytochrome P-450 1A and human NADPH-cytochrome P-450 reductase. AB - Yeast Saccharomyces cerevisiae strains have been constructed that co-express cDNAs coding for the human cytochrome P-450 enzymes CYP1A1 or CYP1A2 in combination with human NADPH-cytochrome P-450 reductase (oxidoreductase). Microsomal fractions prepared from the strains were able to efficiently activate various drugs to Salmonella mutagens. These experiments demonstrated that a functional interaction occurred between the respective human enzymes in the yeast microsomes. For every drug tested, the microsomes containing CYP enzymes and oxidoreductase were 2- to 4-fold better in activation than the corresponding microsomes that contained CYP alone. Interestingly, co-expression of CYP1A2 with oxidoreductase resulted in a decrease of 7-ethoxyresorufin-O-deethylase activity, a problem which is related to this specific substrate. Using the microsomes, it was demonstrated that aflatoxin B1 was activated to a mutagen not only by CYP1A2 but also by CYP1A1. In contrast, benzo[a]pyrene was exclusively activated by CYP1A1 whereas CYP1A2 was inactive. The drug 3-amino-1-methyl-5H-pyrido[4,3 b]indole (Trp-P-2) was activated by CYP1A2 and to a lesser extent by CYP1A1. A strong substrate specificity was observed with the two structurally related heterocyclic arylamines 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2 amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline (MeIQx). MeIQx was activated efficiently by both CYP enzymes, whereas MeIQ was only activated by CYP1A2 and not by CYP1A1. The fact that microsomes from vector transformed control strains were unable to activate any of the drugs studied underlines the suitability of these microsomes for metabolic studies. Moreover, the presence of suitable marker genes in the yeast strains will enable us to study mitotic recombination and gene conversion events induced by drugs that require metabolic activation. PMID- 8200083 TI - Contribution of CYP1A1 and CYP1A2 to the activation of heterocyclic amines in monkeys and human. AB - The activation of heterocyclic amines to mutagenic products by hepatic microsomal fractions from cynomolgus monkey, marmoset monkey and man was compared with the respective levels of cytochrome P450 enzymes CYP1A1 and CYP1A2. The rate of activation of 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3 methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine (PhIP) to mutagens by hepatic microsomal fraction from cynomolgus monkey was very low. This was associated with a lack of constitutive expression of CYP1A1 and CYP1A2. In contrast, human hepatic microsomal fraction readily activates these heterocyclic amines and this is associated with constitutive expression of CYP1A2. Treatment of cynomolgus monkey with 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) causes a very modest induction of CYP1A2, and a small increase in the activation of MeIQx and IQ. However, there was marked induction of CYP1A1 which was accompanied by > 10-fold increases in PhIP activation and 7-ethoxyresorufin O-deethylase (EROD), 7-methoxyresorufin O demethylase (MROD) and aryl hydrocarbon hydroxylase activities. Following treatment of cynomolgus monkey with 3-methylcholanthrene, induction of CYP1A1, but not CYP1A2, was evident. In untreated marmoset monkey the activations of MeIQx and PhIP, as well as phenacetin O-deethylase, EROD, MROD and aryl hydrocarbon hydroxylase activities, are similar to those in man, although the activations of IQ and coumarin 7-hydroxylase activity are lower than in man. The presence of constitutive CYP1A2, and the absence of CYP1A1, in the liver of this species correspond to the situation in man. Treatment of marmoset monkey with TCDD results in increased CYP1A2 levels (4-fold), accompanied by proportional increases in the activation of MeIQx and IQ and phenacetin O-deethylase, EROD and MROD activities. The activation of PhIP is increased disproportionately, by 8 fold, most likely due to the activity of CYP1A1 which is also induced by TCDD in this species. Overall, the hepatic metabolism of heterocyclic amines by CYP1A enzymes in the untreated marmoset monkey resembles that in human more closely than that in the cynomolgus monkey. Therefore, marmoset monkey may be a more suitable model than the cynomolgus monkey for carcinogenicity studies involving MeIQx and PhIP, but not IQ. PMID- 8200085 TI - Activated ras oncogene and specifically acquired resistance to cisplatin in human mammary epithelial cells: induction of DNA cross-links and their repair. AB - A human non-malignant mammary epithelial cell line, HBL100, and the ras transformed HBL100/ras1 cell line were examined for their sensitivity to cis diamminedichloroplatinum(II) (cisplatin). The clonogenic cell survival assay showed that HBL100/ras1 exhibited a 2.7-fold increased resistance compared to the parental HBL100 cell line. The responses to other agents interacting with DNA, such as mitomycin C, 8-methoxypsoralen plus UVA or doxorubicin, were very similar in both cell lines. The same is true for ionizing radiation (Alapetite et al., Int J. Radiat. Biol., 59, 385-396, 1991). In other words, the mechanism of acquired resistance in HBL100 appears to be limited to cisplatin. No difference was observed between the two cell lines in cisplatin uptake as determined by atomic absorption spectrometry. Alkaline elution showed that less interstrand cross-links were formed by this drug in the resistant HBL100/ras1 cells compared to HBL100 and, moreover, the removal of these adducts was clearly more efficient in the former cell line. This was confirmed by an in vitro excision repair assay which revealed a 2.2-fold increase in DNA repair activity in the extracts from HBL100/ras1 versus HBL100 cells. It is concluded that the transformation of human epithelial HBL100 cells by the ras gene resulted in an acquired resistance apparently limited to cisplatin, a feature associated with a reduced proportion of induced interstrand cross-links and a higher efficiency in their removal. The mechanism of involvement of the ras gene product in this process is still a matter of speculation. PMID- 8200086 TI - DNA adduct formation and assessment of aberrant crypt foci in vivo in the rat colon mucosa after treatment with N-methyl-N-nitrosourea. AB - N-Nitroso-compound DNA adduct formation in vivo and occurrence of aberrant crypt foci (ACF) were studied in the rat colon mucosa after a single, local treatment with a carcinogen, N-methyl-N-nitrosourea (MNU), using a simple surgical approach. A segment of F344 rat colon was ligated to make a pouch and injected with MNU solution. For the study of DNA adduct formation, the solution contained 50 microCi of [3H]MNU. The results demonstrated that similar ranges of carcinogen dose, i.e. 0.15 x 10(-2) - 1.5 x 10(-2) M MNU, could induce both DNA adduct formation and appearance of ACF in the rat colon with both parameters showing a nearly linear dose dependence. HPLC analysis revealed the DNA adducts to include both 7-methylguanine (7-mGua) and O6-methylguanine (O6-mGua) with the 7-mGua/O6 mGua ratio being 8.2-11.3:1 in the system used. Assessment of ACF development from 4 to 16 weeks after MNU treatment at a dose of 7.5 x 10(-2) M showed the numbers to increase up to the 8th week, followed by a decrease at weeks 12 and 16, when 40% of the ACF counted at the peak time point were still present. The percentage of large ACF (> or = 4 crypts/ACF) significantly increased with time. These results indicate a clear relation between DNA adducts and preneoplastic lesions, i.e. ACF. In conclusion, DNA adduct formation and ACF can be efficiently and simply detected in vivo by using the method described in the present paper. PMID- 8200087 TI - Intestinal microflora enhances formation of DNA adducts following administration of 2-NF and 2-AAF. AB - 2-Nitrofluorene (NF) is found in the environment mainly due to incomplete combustion, as in vehicles. The major class of metabolites in vivo in rats after oral administration is the reduced and acetylated metabolites, e.g. derivatives of 2-acetylaminofluorene (AAF). The intestinal microflora reduces the nitro function to an amine which is further metabolized via acetylation and hydroxylations. In this study, NF and AAF were orally administered to germ-free and conventional rats with the aim of studying DNA adduct formation in different tissues with the 32P-post-labelling assay. Chromatographic detection was performed with TLC and on-line 32P detection after HPLC separation of DNA adducts. The major (95%) DNA adduct formed was dG-C8-AF for both NF and AAF. The potency to form DNA adducts successively declined with the combinations conventional/AAF, germ-free/AAF, conventional/NF and germ-free/NF. The DNA adduct dG-C8-AF was detected in all four tissues that were analysed, e.g. liver, kidney, lung and heart. The presence of intestinal microflora enhanced the formation of DNA adducts in the tissues studied. PMID- 8200088 TI - Alterations of drug metabolizing and antioxidant enzyme activities during tamoxifen-induced hepatocarcinogenesis in the rat. AB - The triphenylethylene drug tamoxifen is a hepatocarcinogen in rats, has genotoxic potential and may produce carcinoma of the endometrium in humans, while the structurally closely related toremifene has no carcinogenic or genotoxic potential. We have investigated the effects of long-term treatment with tamoxifen and toremifene on the activities of drug metabolizing and antioxidant enzymes in rat liver. Female Sprague-Dawley rats were dosed with equimolar doses of tamoxifen (11.3 and 45 mg/kg) and toremifene (12 and 48 mg/kg) for 12 months and were killed after 2 days, 5 weeks, 3, 6 and 12 months of treatment. After 12 months most rats treated with the high dose of tamoxifen had hyperplastic nodules and hepatocellular carcinomas, while in rats given toremifene or the low dose of tamoxifen, only foci were observed. A striking observation was strong inhibition of the hexose monophosphate shunt (HMS) by tamoxifen and toremifene, which, except in the group given the high dose of tamoxifen, lasted throughout the treatment period. Both antiestrogens induced susceptibility to oxidative stress, as indicated by decreased hepatic contents of reduced glutathione and by increased peroxidation potential of microsomal preparations. The activity of glutathione S-transferase was permanently induced by the high dose of tamoxifen from 5 weeks onwards and was greater in tamoxifen-induced liver tumors than in corresponding macroscopically normal tissue. Similarly, the activity of HMS was elevated by the high dose of tamoxifen at the latest time points, and a further elevation was seen in tamoxifen-induced liver tumors. No such alteration in glutathione S-transferase or HMS activity was seen in animals treated with toremifene or with the low dose of tamoxifen. In conclusion, tamoxifen and toremifene differ markedly with respect to production of liver tumors, and this difference in hepatocarcinogenic potential is reflected in differential effects on glutathione-S-transferase and HMS activities in rat liver. PMID- 8200089 TI - Mutation spectra of 1,2-dibromoethane, 1,2-dichloroethane and 1-bromo-2 chloroethane in excision repair proficient and repair deficient strains of Drosophila melanogaster. AB - DNA sequence changes produced by 1,2-dibromoethane (DBE), 1,2-dichloroethane (DCE) and 1-bromo-2-chloroethane (BCE) were analyzed using the vermilion locus of Drosophila melanogaster. Under excision repair proficient (exr+) conditions (mutagenized exr+ males mated with exr+ females) all mutants isolated from the first generation (F1) after DBE and DCE exposure represented DNA rearrangements (multi-locus deletions, small deletions with tandem repeats, duplicate insertions). By contrast, mutants expressing a vermilion phenotype only in the F2 (F1 mosaics) all carried single bp changes. When exr+ males, after exposure to DBE, were mated to excision repair deficient (exr-) mus 201 females 11 of 14 mutational events isolated from either F1 or F2 progeny were single bp changes. In general the mutation spectra for the three dihaloalkanes were similar to the spectrum obtained at the same locus for the direct-acting monofunctional agent methylmethanesulfonate (MMS). The data lend support to the conclusions that these 1,2-dihaloalkanes are genotoxic through modification at ring nitrogens in DNA, primarily at the N7 of guanine and, to a lesser extent, at the N1 of adenine. These N-adducts could be directly miscoding. However, more important for the mutagenic action of the chemicals seems to be the formation of non-coding lesions and/or misrepair. PMID- 8200090 TI - 32P-post-labelling analysis of DNA adducts formed by food-derived heterocyclic amines: evidence for incomplete hydrolysis and a procedure for adduct pattern simplification. AB - Food-derived aminoimidazoazarenes have been shown to be mutagenic and carcinogenic and to form covalent DNA adducts. 32P-Post-labelling analysis of DNA modified with these heterocyclic amines (HA), including 2-amino-3-methyl imidazo[4,5-f]quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,4-dimethylimidazo [4,5-f]quinoline (MeIQ), 2-amino-3,7,8 trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx) and 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline (MeIQx) has resulted in considerable interlaboratory variation in the characteristic patterns of DNA adduct spots, with up to six being detected for each compound. Similar complex patterns were observed when azido-derivatives of HA were photoreacted with calf thymus DNA. When deoxyguanosine 3'-monophosphate was modified with the azido derivatives and analysed using the 32P-post-labelling procedure, one major spot was observed for IQ, 4,8-DiMeIQx, 7,8-DiMeIQx or PhIP and two major spots for MeIQ or MeIQx. In each case, these adducts were chromatographically indistinguishable from the major adducts formed with DNA. No major adduct spots were observed when 3' phosphate derivatives of deoxyadenosine, deoxycytidine or thymidine were reacted with the azido-derivatives of HA. In an attempt to identify the additional spots, azido derivatives of PhIP or IQ were reacted with the synthetic homopolymer poly(dG).poly(dC), the alternating copolymer poly(dC-dG) or a synthetic oligonucleotide (TTT-GTTTTTTCTTTCCCT): in each case a reduced number of adduct spots were detected. The introduction of an additional nuclease P1 hydrolysis step following the labelling reaction further reduced the number of adduct spots to only one or two major spots. Reversed-phase HPLC analysis showed that the number of peaks of radioactivity was also reduced to one or two, presumably corresponding to the [32P]-5'-monophosphate deoxyguanosine adducts. We suggest that many of the additional spots commonly observed in conventional 32P-post labelling analysis of HA-modified DNA are adducted oligonucleotides that are partly resistant to hydrolysis by micrococcal nuclease and spleen phosphodiesterase but are susceptible to hydrolysis by nuclease P1. PMID- 8200091 TI - Effect of catechol and ethanol with and without methylamylnitrosamine on esophageal carcinogenesis in the rat. AB - Alcohol consumption and cigarette smoking are synergistic etiologic factors for squamous cell carcinoma of the esophagus in Western countries. Catechol, a constituent of cigarette smoke, was previously found to be a co-carcinogen with methyl-n-amylnitrosamine (MNAN) for esophageal tumors in rats, when it was given in the diet. Here we tested whether the inclusion of ethanol in a similar system had an additional promoting effect on esophageal carcinogenesis. Male MRC - Wistar rats were injected three times i.p. with 25 mg MNAN/kg starting from 7 weeks of age. A second group of rats was injected similarly with MNAN and treated for life with 10% ethanol and 0.2% catechol in the drinking water, starting at 6 weeks of age. One or more test chemicals were omitted in other groups. The rats were maintained until they died and were necropsied. The number of esophageal papillomas/rat was 2.18 +/- 0.36, 4.27 +/- 0.53, 2.54 +/- 0.48 and 3.21 +/- 0.52 (mean +/- SE) in groups treated with MNAN alone, MNAN + ethanol + catechol, MNAN + ethanol and MNAN + catechol, respectively. Esophageal carcinomas showed a similar trend, with the number of carcinomas/rat equal to 0.23 +/- 0.08 in the MNAN alone group and 0.50 +/- 0.14 in the MNAN + ethanol + catechol group. Tumor multiplicities for the esophageal papillomas and carcinomas were significantly (P < 0.05) greater in the MNAN + ethanol + catechol group than in the MNAN group. These findings indicate that, in the esophagus, catechol alone was not significantly co-carcinogenic with MNAN when it was given in the drinking water (unlike when given in the diet in our previous study), but that ethanol + catechol given in the water was co-carcinogenic with MNAN. Seven of 19 rats given ethanol + catechol without MNAN developed esophageal papillomas, as compared to zero incidence in untreated controls (P = 0.06). Forestomach papillomas occurred in 22% of all rats given catechol. Hence, for esophageal tumor induction, ethanol and catechol were co-carcinogenic with MNAN and appeared to be tumorigenic when given without MNAN. Ethanol and catechol could have increased the carcinogenicity because they affected MNAN metabolism. As a partial test of this possibility, the effect of feeding these compounds for 5-7 weeks separately or together was examined on 2-, 3-, 4-and 5-hydroxy-MNAN (HO-MNAN) production from MNAN by the esophagus and liver slices from freshly killed rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8200092 TI - Mutations induced by aromatic amine DNA adducts in pBR322. AB - A 276 bp region from the tetracycline resistance gene of the plasmid pBR322 was modified with 2-acetylaminofluorene (AAF), 2-aminofluorene (AF), 4-aminobiphenyl (ABP), N'-acetylbenzidine or 1-aminopyrene (AP) in order to determine the effect of adduct structure upon mutation induction. Each modification reaction gave one major adduct and these adducts had chromatographic properties, as determined by 32P-postlabeling, identical to those in which substitution had occurred at C8 of deoxyguanosine through the amine or amide nitrogen. The types and distribution of mutations were then characterized following introduction of the modified plasmids into SOS-induced Escherichia coli using Hanahan et al.'s procedure (Methods Enzymol., 204, 63-113, 1991). With AAF-modified plasmid, 60% of the mutations were deletions or additions, and these were detected primarily at NarI sites or in repetitive G sequences. Modification with AF gave -G deletions, primarily in runs of Gs, and base substitution mutations, which were mainly G to T transversions. Substitution with ABP or N'-acetylbenzidine resulted in G to T and G to C transversions, the latter being a mutation not detected with AF; in addition, -G deletions were detected at only very low frequency. AP modification gave both -G frameshift and base substitution mutations, of which G to T transversions predominated. A comparison of the mutation frequencies per adduct indicated that the mutagenic efficiencies of the adducts decreased in the order AP > AF > AAF approximately ABP approximately N'-acetylbenzidine. AAF- and ABP modified pBR322 were also introduced with a CaCl2 method. The mutation frequency per adduct increased with this transformation procedure, and this appeared to be a reflection of a greater percentage of frameshift mutations. These data indicate that a series of structurally related aromatic amines will induce both base substitution and frameshift mutations when incorporated into pBR322, but that frameshift mutations occur almost exclusively with the planar derivatives. Furthermore, the ability to induce frameshift mutations increases the mutagenic efficiency of an adduct. PMID- 8200093 TI - Presence of mucosa-specific DNA adduct in human colon: possible implication for colorectal cancer. AB - DNA of normal mucosa and the adjacent muscular layer from 18 adults suffering from colorectal neoplasms was examined by 32P-post-labeling analysis in order to estimate the exposure of the human colon and rectum to environmental carcinogens. Colorectal DNA samples obtained from six newborns were also examined as a normal control because they were presumed to have been minimally exposed to environmental carcinogens. One common mucosa-specific DNA adduct was found in the normal colorectal wall in all adults at the level of 0.10-34.13 adducts/10(8) nucleotides (mean +/- SD: 3.64 +/- 7.92 adducts/10(8) nucleotides), however, these were absent from the newborns' colons. Although several common spots were present in the mucosa, muscular layer and newborn tissues, there was no muscular layer-specific DNA adduct. The relationship between the levels of the mucosa specific DNA adduct in the non-cancerous part and the histological degree of malignancy was not significant. The presence of this mucosa-specific DNA adduct in adult colon suggests that the human colon is commonly exposed mainly to one environmental carcinogen. This carcinogen is supposed to originate from foods, because the incidence of colorectal carcinoma is closely linked to dietary habits and the mucosa-specific DNA adduct was not present in newborns who had never ingested food. The incidence of adult colonic cancer originating from its mucosa is high, while cases of muscular origin or in newborn colon are rare. Therefore, the mucosa-specific DNA adduct is presumably responsible for the development of colonic cancer of epithelial origin. PMID- 8200094 TI - Separation and characterization of post-labeled DNA adducts of stereoisomers of benzo[a]pyrene-7,8-diol-9,10-epoxide by immobilized boronate chromatography and HPLC analysis. AB - The carcinogenic polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP) is enzymatically activated in cells to an ultimate carcinogenic metabolite, benzo[a]pyrene-7,8-dihydrodiol-9,10- epoxide (BaPDE), which reacts with DNA to form covalent adducts involved in the initiation of cancer. Previously, a post labeling procedure that uses adenosine-5'-O-(3'-[35S]-thiotriphosphate) was developed to facilitate adduct analysis by HPLC. The much greater carcinogenic potency of (+)-anti-BaPDE makes it essential to be able to separate and identify the adducts formed by all four BaPDE enantiomers in DNA of cells exposed to BaP. Reversed-phase HPLC (RPHPLC) resolved the major (+)-anti-BaPDE-N2-deoxyguanosine [(+)-anti-BaPDE-N2-dG] adduct from the (+)-syn-BaPDE-N2-dG adduct. However, anti BaPDE-N2-dG adducts formed by (+)- and (-)-anti-BaPDE were not resolved. By using ion-pair RPHPLC (IP-RPHPLC) with tetrabutylammonium phosphate, the [35S]post labeled (-)-anti-BaPDE-N2-dG adduct eluted 3 min prior to the [35S]labeled (+) anti-BaPDE-N2-dG adduct. In contrast, the major syn-BaPDE-N2-dG adducts were resolved better by RPHPLC than by IP-RPHPLC. The difference in conditions required for optimal separation of anti- and syn-BaPDE-DNA adducts necessitated the development of an immobilized boronate chromatography technique for the separation of anti- from syn-BaPDE-DNA adducts prior to analytical HPLC analysis. At 4 degrees C and with elution buffers containing high salt concentrations, the [35S]post-labeled anti-BaPDE-DNA adducts were selectively retained by a boronate column whereas the [35S]labeled syn-BaPDE-DNA adducts were not. Analysis of the multiple BaP-DNA adducts formed in BaP-treated hamster embryo cells by these techniques gave results comparable to those obtained by other methods. The major BaP-DNA adducts were anti-BaPDE-N2-dG, 14% from (-)- and 86% from (+)-anti-BaPDE. The ability of these techniques to detect low levels of PAH-DNA adducts because of the high specific radioactivity of 35S and to separate the DNA adducts formed by stereoisomeric PAH diol epoxides adducts by boronate by stereoisomeric PAH diol epoxides adducts by boronate chromatography and HPLC will facilitate studies of the role of individual PAH-DNA adducts in the induction of biological effects such as toxicity and carcinogenesis. PMID- 8200095 TI - Inhibitory effect of vitamin C on the mutagenicity and covalent DNA binding of the electrophilic and carcinogenic metabolite, 6-sulfooxymethylbenzo[a]pyrene. AB - 6-Sulfooxymethylbenzo[a]pyrene has recently been shown to be a strong hepatocarcinogen in infant male B6C3F1 mice (Y.-J.Surh et al., Biochem. Biophys. Res. Commun., 172, 85-91, 1990) and appears to be an ultimate carcinogenic metabolite of 6-hydroxymethylbenzo[a]pyrene and possibly of benzo[a]pyrene. It produced high levels of aralkyl DNA adducts in the livers of B6C3F1 mice and also exhibited strong direct mutagenicity toward Salmonella typhimurium TA98 without metabolic activation. In the present study we found that ascorbic acid significantly reduced the bacterial mutagenicity and in vitro covalent DNA binding of 6-sulfooxymethylbenzo[a]pyrene. Ascorbic acid forms a mutagenically inactive covalent adduct with 6-sulfooxymethylbenzo[a]pyrene, which appears to account for its novel protective mechanism against this reactive sulfuric acid ester. It seems likely that the formation of this adduct involves aralkylation of an ascorbic acid anion by a presumed carbo cation derived from the electrophilic sulfuric acid ester. PMID- 8200096 TI - Ectopic pituitary grafts modify the response of male rats to sex differentiated promotion of diethylnitrosamine-initiated hepatic lesions with a choline deficient diet. AB - The influence of implantation of ectopic pituitary grafts (PGs) under the kidney capsule in male rats on the sex differences in response to promotion with a choline-deficient (CD) diet was studied in the livers of diethylnitrosamine (DEN) initiated Wistar rats. Growth of enzyme-altered foci, liver regeneration in response to partial hepatectomy (PH) and hepatic c-myc expression were studied. The area per enzyme-altered focus was significantly larger in initiated males fed a CD diet for 10 weeks when compared with the corresponding females. The sex difference was more pronounced 1 week after a PH performed following 10 weeks on the diet. In males carrying PGs the area per focus was reduced to the same size as in females. Liver weight gain after PH was reduced in males, but not in females, by the CD diet, and the level in PG-bearing males was intermediary, significantly different from that of males without grafts. A significantly lower labeling index in surrounding, but not in focal, hepatocytes was observed in initiated, CD-treated males than in the corresponding females 1 week after PH. In initiated as well as in uninitiated males on a CD diet the expression of the c myc gene was 3- to 4-fold higher when compared with males fed a choline supplemented diet at the time of PH. The mRNA level in females fed a CD diet was approximately 2.5-fold lower than in males, but still significantly above the level in females without the dietary treatment. A significant decrease in male c myc expression was observed as a result of implantation of ectopic pituitaries. In conclusion, sex-differentiated promotion of DEN-initiated lesions with a CD diet is regulated by a pituitary influence on rat liver, in analogy with results previously obtained in the resistant hepatocyte model and with dietary deoxycholic acid promotion. This might suggest that pituitary factors are major determinants of sex-differentiated promotion in rat liver. PMID- 8200097 TI - Mutagenic activity of gastric fluid from chewers of tobacco with lime. AB - Although tobacco chewing is strongly associated with a high risk of oral and upper alimentary tract cancers, the nature of mutagenic exposure among users has not been clearly defined. In this study, tobacco-specific and mutagenic exposure of chewers of tobacco with lime was evaluated by analysis of gastric fluid (GF). The pH, nitrite and cotinine levels of GF samples from chewers and non-chewers were determined and the samples were tested for mutagenicity in the Ames Salmonella/microsome assay using Salmonella typhimurium strains TA98, TA100 and TA102. Cotinine was not detected in GF from non-chewers while the levels ranged between 0.4-13.64 micrograms/ml in samples from chewers; however, the mean pH values (3.8 +/- 0.4 versus 2.8 +/- 0.3) and nitrite levels (29.40 +/- 1.51 versus 27.39 +/- 0.83 microM) were similar in both groups. While all GF samples from non chewers were non-mutagenic, samples from chewers were directly mutagenic or upon nitrosation to all the three tester strains and to TA102 strain in the presence of S9. Experiments using scavengers of reactive oxygen species (ROS) showed that mannitol and benzoate abolished the mutagenic response of TA102, indicating that ROS are principally responsible for oxidative damage. The findings provide specific information regarding the mutagenic exposure among tobacco chewers and suggest that tobacco chewing may be an important risk factor in the development of gastric cancer. PMID- 8200098 TI - Restoration of aryl hydrocarbon (Ah) responsiveness in MDA-MB-231 human breast cancer cells by transient expression of the estrogen receptor. AB - MDA-MB-231 human breast cancer cells express the aryl hydrocarbon (Ah) receptor; however, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) does not induce CYP1A1 gene expression or chloramphenicol acetyltransferase (CAT) activity in cells transiently transfected with pRNH11c, and Ah-responsive plasmid derived from the 5'-flanking region of the human CYP1A1 gene. However, when MDA-MB-231 cells were treated with 10 nM TCDD and co-transfected with pRHN11c and a human estrogen receptor (hER) expression plasmid (delta hER), there was approximately a 10-fold increase in CAT activity. The restoration of Ah-responsiveness in MDA-MB-231 cells by expression of nuclear hER was highly specific since parallel studies in which plasmids that express the progesterone receptor and Jun nuclear proteins did not restore Ah-responsiveness to this cell line. Moreover, in cells transiently transfected with the pRNH11c and delta hER plasmids and 10 nM TCDD, overexpression of the Jun protein inhibited the effects of the hER on Ah responsiveness. Plasmids that express truncated forms of the hER were also active in MDA-MB-231 cells but were not as effective as the complete hER. These studies reveal a unique function for the ER in MDA-MB-231 cells in which expression of this protein results in restoration of Ah-responsiveness. PMID- 8200099 TI - Comparison of mutation spectra induced by N-ethyl-N-nitrosourea in the hprt gene of Mer+ and Mer- diploid human fibroblasts. AB - N-Ethyl-N-nitrosourea (ENU) forms several major adducts upon reaction with DNA, of which ethylation at the O6 position of guanine and the O4, O2 and N3 positions of thymine have been implicated to be mutagenic lesions. To investigate what specific kinds of ENU-induced mutations were affected by the repair ability of O6 alkylguanine-DNA alkyltransferase (AGT), we examined the mutations in the hypoxanthine (guanine) phosphoribosyltransferase gene (hprt) in 87 independent mutants derived from ENU-treated AGT proficient (Mer+) or deficient (Mer-) diploid human fibroblasts. Of the characterized mutations, 97% were single base substitutions. The major difference in the mutation spectra was that the frequency of G.C to A.T transitions was significantly higher in Mer- mutants (16/38) than in Mer+ mutants (4/33). The results indicate that AGT removes O6 ethylguanine, thus protecting human cells from parts of the cytotoxic and mutagenic effects of ENU. A high frequency of T.A to A.T transversions induced by ENU was observed in both Mer+ (52%) and Mer- (34%) mutants. This type of mutation was less frequently observed (10%) in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced mutants derived from the same Mer+ cells in our previous report (J. Mol. Biol., 221, 421, 1991). Comparison of alkylating lesions formed by MNNG and ENU indicates that O2-ethylthymine and N3-ethylthymine are potent mutational adducts for T to A transversions. The occurrence of ENU-induced T.A base pair transversions showed a strong strand bias; 35/37 were located on the non transcribed strand, assuming thymine is the mutagenic lesion. The result suggests a difference in repair capacity of ethylthymine on the two strands. In addition, this type of mutation preferentially occurred at 5'-Pu-T sequences. PMID- 8200100 TI - Hepatic and extrahepatic bioactivation and GSH conjugation of aflatoxin B1 in sheep. AB - Whole-body autoradiography of [3H]aflatoxin B1 ([3H]AFB1) in lamb showed a localization of bound labelling, in addition to the liver, in the nasal olfactory and respiratory mucosa, in the mucosa of the nasopharynx, pharynx, oesophagus, larynx, trachea, bronchi and bronchioles and in the palpebral and bulbar conjunctiva. Microautoradiography revealed that the bound material was confined to specific cell types in extrahepatic tissues. Whole-body autoradiography also showed a labelling of pigmented tissues (such as the eye melanin), which can be ascribed to a melanin affinity of AFB1. In vivo experiments, performed with microsomal preparations of tissues from ewe and lamb showed that several of the extrahepatic tissues were more efficient than the liver in forming DNA-bound AFB1 metabolites. The nasal olfactory mucosa was by far the most effective tissue in this respect. AFB1 induced a high number of gene mutations in Salmonella typhimurium TA100 when incubated with supernatant preparations (9000 g) of the nasal olfactory mucosa, whereas incubations with preparations of the liver resulted in a lower effect. It has been reported that AFB1 can induce nasal tumours in sheep. When microsomal preparations of various tissues were incubated in the presence of reduced glutathione (GSH), but without any addition of cytosolic glutathione-S-transferase (GST), a drastic decrease in the AFB1-DNA binding was seen. Analyses of the water-soluble metabolites formed in the microsomal incubations supplemented with GSH showed fluorescent and ninhydrin positive metabolites that were not present in the absence of GSH. These results indicate that sheep tissues have intrinsic microsomal GST or cytosolic GSTs associated with the microsomal fraction with a high capacity to catalyse the conjugation of bioactivated AFB1 to GSH. The results of the present study show that several extrahepatic tissues of sheep have a potent capacity to bioactivate AFB1 and also a high capacity to GSH conjugate the bioactivated AFB1. PMID- 8200101 TI - Preparation of compound-specific and group-specific antibodies to 7-methylguanine and related 7-alkylguanines and their use in immunoaffinity purification. AB - The preparation and characteristics of compound-specific and group-specific antibodies against 7-alkylguanines (7-alkGua) are described. A compound-specific antibody against 7-methylguanine was prepared using a hapten bound to carrier protein through the N2 position. In a competitive enzyme-linked immunosorbent assay (ELISA) 7-methylguanine (7-MeGua) showed 50% inhibition (I50%) at 10 pmol/well at room temperature, but the inhibition was found to be 40 times better at 4 degrees C (I50% at 250 fmol/well). When the antibody was bound to protein A Sepharose CL4B 7-MeGua was retained in immunoaffinity columns. A group-specific antibody to 7-alkGua was prepared using 7-(2-carboxyethyl)guanine (7-CEGua) bound to carrier protein via the carboxyl group. In a competitive ELISA, this antibody cross-reacted well with 7-CEGua, 7-ethylguanine (7-EtGua), 7-(2 hydroxyethyl)guanine (7-HOEtGua) and 7-(2',3'-dihydroxy)-propylguanine (7-DHPGua) and some inhibition was seen with 7-MeGua. Immunoaffinity columns prepared from this antibody retained a number of 7-alkGua of diverse structure. 7-EtGua in calf thymus DNA treated with diethylsulphate and ethylnitrosourea was isolated by immunoaffinity purification and quantified by HPLC-fluorescence. These results illustrate the potential of immunoaffinity purification for both individual DNA adducts and groups of adducts. PMID- 8200103 TI - In vitro cytotoxicity of asbestos and man-made vitreous fibers: roles of fiber length, diameter and composition. AB - The present study investigated (i) the impact of various fiber parameters on in vitro toxicity to cells and (ii) the validity of an in vitro test system as a toxic screen for fibrous materials. Chinese hamster ovary cells were exposed in vitro to a series of size-selected inorganic test fibers that represented a range of different diameters, lengths and compositions (glass, refractory ceramic, mineral wool, asbestos). Toxic end-points included inhibition of proliferation, induction of micronuclei and polynuclei and viability. For all compositions tested, toxic effects were similar: a concentration-dependent decrease in proliferation and increase in incidence of morphologically abnormal nuclei with minor decreases in viability. Diameter-dependent differences in toxicity were slight or absent for fiber diameters ranging from 0.3-7 microns when concentration was expressed as number of fibers/cm2. Length-dependent differences in toxicity were, however, striking. EC50 values (concentration in fibers/cm2 that reduced cell proliferation to 50% of unexposed control cultures) plotted against fiber length produced a hyperbolic curve, demonstrating that toxicity increases with fiber length up to 20 microns. All fibers tested fell on this hyperbola. These data suggest that: (a) the primary toxic effect of fibers on CHO cells is the induction of nuclear morphologic alterations resulting in cytostasis; (b) fiber diameter has little or no impact on in vitro toxicity when concentration is calculated as fibers/cm2; (c) fiber length is directly proportional to in vitro toxicity; and (d) toxicity of asbestos and vitreous fibers to CHO cells is not affected by composition. The lack of compositional effect in CHO cells does not correlate with findings from recent rodent inhalation studies using the same test fibers. Thus CHO cells may not be an appropriate in vitro model of fiber pathogenesis and would not constitute a valid toxicologic screening system for fibers. PMID- 8200102 TI - DNA contents and chromosomes of clonal lines of transformed rat liver epithelial cells and of cells from their derived tumors. AB - Clonal lines of transformed rat liver epithelial cells, derived from a single population of cloned diploid rat liver epithelial (stem-like) cell line (WB-F344) by exposure in vitro to N-methyl-N'-nitro-N- nitrosoguanidine (MNNG), produce hepatocellular carcinomas, hepatoblastomas and adenocarcinomas in syngeneic rats (Tsao and Grisham, Am. J. Pathol., 127, 168-181, 1987). In this study we show that these clonal lines demonstrate near-diploid (GN clones) or near-triploid (GP clones) aneuploidy and the universal occurrence of non-random chromosomal abnormalities. Marker chromosomes that involved four autosomes--a non-reciprocal translocation involving chromosomes 1 and 7 (t1q43;7q34), and addition of DNA of unknown origin to the pericentromeric regions of chromosomes 4 and 10--occurred in all of the cells of all transformed clones and in the cells of tumors that grew from them. New marker chromosomes involving the same regions of chromosomes 4 and 7 were found in several cell lines established from independent tumors. The preservation of marker chromosomes in tumor cells in the face of random loss and gain of other chromosomes suggests that these non-random aberrations were necessary for tumor formation. The presence of marker chromosomes was associated with increased expression of the c-myc gene (located at q34 on chromosome 7), the c-H-ras gene (located at q41-43 on chromosome 1) and the c-K-ras and TGF alpha genes (both located at unknown sites on chromosome 4), which we have previously shown to be highly correlated with tumorigenicity in these same transformed clonal lines (Lee et al., Cancer Res., 51, 5238-5244, 1992). PMID- 8200104 TI - A 32P-postlabeling method for simultaneous detection and quantification of exocyclic etheno and propano adducts in DNA. AB - A 32P-postlabeling method is described that specifically detects and quantifies the 1,N2-propanodeoxyguanosine adducts derived from acrolein (AdG) and crotonaldehyde (CdG) and 1,N2-ethenodeoxyguanosine (EdG) in DNA. These exocyclic adducts are potential DNA lesions caused by exposure to enals as environmental pollutants and as endogenous compounds. This method was developed with the use of the synthetic adduct standards of these exocyclic adducts. The assay relies on HPLC for adduct enrichment prior to labeling and for quantitation and identification after labeling. The labeling efficiencies of adducts at the 1 fmol level ranged from 74 to 96%, whereas they were only 49-60% at the 100 fmol level. This method can detect as low as 0.2 fmol of adduct and allows the detection and quantitative determination of stereoisomers of AdG and CdG. The method was validated by using a sample of enzyme digests of 180 micrograms calf thymus DNA spiked with 25 or 75 fmol of adducts, which is equivalent to 5 or 15 adducts in 10(8) nucleotides. The recovery rates of these adducts in DNA ranged from 30 to 90% at the 25 fmol level and 21 to 55% at the 75 fmol level. Similar to the labeling efficiency, a greater recovery was observed with a lower amount of adduct in DNA. Overall, this method allows the simultaneous identification and quantification of exocyclic adducts AdG, CdG and EdG in DNA. Therefore, it provides a potential tool for studies of the in vivo formation of exocyclic adducts. PMID- 8200105 TI - Pathobiological effects of acetaldehyde in cultured human epithelial cells and fibroblasts. AB - The ability of acetaldehyde, a respiratory carcinogen present in tobacco smoke and automotive emissions, to affect cell viability, thiol status and intracellular Ca2+ levels and to cause DNA damage and mutations has been studied using cultured human cells. Within a concentration range of 3-100 mM, a 1 h exposure to acetaldehyde decreases colony survival and inhibits uptake of the vital dye neutral red in bronchial epithelial cells. Acetaldehyde also causes both DNA interstrand cross-links and DNA protein cross-links whereas no DNA single strand breaks are detected. The cellular content of glutathione is also decreased by acetaldehyde, albeit, without concomitant changes in the glutathione redox status or in the content of protein thiols. Transient or sustained increases in cytosolic Ca2+ occur within minutes following exposure of cells to acetaldehyde. Moreover, acetaldehyde significantly decreases the activity of the DNA repair enzyme O6-methylguanine-DNA methyltransferase. Finally, a 5 h exposure to acetaldehyde causes significant levels of 6-thioguanine resistance mutations in an established mutagenesis model involving skin fibroblasts. The results indicate that mM concentrations of acetaldehyde cause a wide range of cytopathic effects associated with multistep carcinogenesis. The fact that acetaldehyde, in relation to its cytotoxicity, causes comparatively higher genotoxicity and inhibits DNA repair more readily than other major aldehydes in tobacco smoke and automotive emissions is discussed. PMID- 8200106 TI - Relationship between hepatic DNA damage and methylene chloride-induced hepatocarcinogenicity in B6C3F1 mice. AB - Methylene chloride (MC) induced DNA damage in freshly isolated hepatocytes from mice and rats, which was detectable as single-strand (ss) breaks by alkaline elution. The lowest in vitro concentration of MC needed to induce DNA damage in mouse hepatocytes (0.4 mM) was much lower than for rat hepatocytes (30 mM), and is close to the calculated steady-state concentration of MC in the mouse liver (1.6 mM) at a carcinogenic dose (4000 p.p.m. by inhalation). DNA ss breaks were also detectable in hepatocyte DNA from mice which had inhaled 4000 p.p.m. MC for 6 h, but not in hepatocyte DNA from rats similarly exposed. In studies with hepatocytes cultured overnight in the presence of buthionine sulfoximine to deplete glutathione (GSH), subsequent exposure to MC resulted in less DNA damage in the GSH-depleted cells. This shows that conjugation of MC with GSH is important in its activation of DNA-damaging species in the liver. The GSH pathway of MC metabolism produces two potential DNA-damaging species, formaldehyde and S chloromethylglutathione (GSCH2Cl). Formaldehyde is known to cause DNA ss breaks in cells. However, the lowest concentration of formaldehyde required to induce a significant amount of DNA ss breaks in mouse hepatocytes (0.25 mM) is unlikely to be formed following in vitro or in vivo metabolism of MC at concentrations that induce similar amounts of DNA damage. That formaldehyde does not play a role in this DNA damage has been confirmed in experiments with CHO cells exposed to MC and an exogenous activation system from mouse liver (S9 fraction). Formaldehyde was responsible for the DNA- protein cross-linking effect of MC, but did not cause the DNA damage leading to ss breaks. These DNA ss breaks are likely to be caused by GSCH2Cl. The results suggest a genotoxic mechanism for MC carcinogenicity in the mouse liver, and support the proposal that the observed species differences in liver carcinogenicity result from differences in the amount of MC metabolism via the GSH pathway in the target organ. PMID- 8200107 TI - DNA single-strand breaks in kidneys of Syrian hamsters treated with steroidal estrogens: hormone-induced free radical damage preceding renal malignancy. AB - The chronic administration of estradiol by subcutaneous (s.c.) implantation into male Syrian hamsters induces kidney tumors. Free radicals generated by redox cycling between catecholestrogens and their quinones have been proposed to damage DNA and to thus mediate renal hormone-induced carcinogenesis. As part of an examination of this postulate, we assayed by a filter elution technique DNA single-strand breaks in livers and kidneys of male hamsters treated with estrogen by single intraperitoneal (i.p.) injection, by s.c. implant or by continuous infusion and compared values to those in untreated controls. The DNAs of hamster liver and kidney were not affected by one i.p. injection of 5, 15 or 150 mg/kg estradiol. However, treatment of hamsters with one 25 mg estradiol implant/animal for 2 weeks elevated by 10% the levels of DNA single-strand breaks in kidney, but only to a minor extent in liver, which is not a target of estrogen-induced carcinogenesis. An infusion of 250 micrograms/day/animal of estradiol or 4 hydroxyestradiol for one week by osmotic pumps into hamsters resulted in a comparable increase of single-strand breaks in kidney DNA, whereas 2 hydroxyestradiol under these conditions had a negligible effect. It is concluded that the induction of DNA single-strand breakage by either estradiol or 4 hydroxyestradiol in hamster kidney supports a mechanism of estrogen-induced carcinogenesis by free radical generation via redox cycling between 4 hydroxyestradiol and its corresponding quinone. PMID- 8200108 TI - Beyond the umbilical cord: interpreting laboratory tests in the neonate. AB - Interpretation of biochemical testing in the neonatal period is challenging because of the complexity of perinatal physiology, the difficulty of establishing appropriate laboratory reference ranges, and the technical aspects of analyzing microvolume specimens that are often hemolyzed, lipemic, or have a high hematocrit or bilirubin concentration. Metabolic problems such as hyperbilirubinemia and hypoglycemia in the full-term neonate occur as the infant adapts from an intrauterine metabolism to extrauterine life. Pathophysiological processes in the premature infant vary with the severity of prematurity and the immaturity of metabolic systems. Interpreting neonatal biochemistry requires age- and gestation-specific reference ranges but technical, ethical, and philosophical concerns continue to impair the development of the needed reference data. PMID- 8200109 TI - Effect of assay conditions on measurement of elastolytic activity of alveolar macrophages in culture and characterization with proteinase inhibitors. AB - We have investigated whether varied assay conditions account for the conflicting reports on measured elastolytic activity of alveolar macrophages (AM) cultured in direct contact with the 3H-elastin substrate coated onto 16-mm wells in serum containing media. The data indicate that measured elastolytic activity in this assay system was dependent on the amount of 3H-elastin/culture well. 3H-elastin > 350 micrograms/well, in contrast to the < or = 200 micrograms/well commonly used in this assay system, resulted in optimal measurement of elastolytic activity that was linear with respect to culture time (up to 72 h examined) and was directly proportional to number of AM/well (up to 1.0 x 10(6) examined). The sensitivity of measured elastolytic activity to tissue inhibitor of metalloproteinases (TIMP) and to Z-phe-phe (a specific cysteine proteinase inhibitor) was not affected by amount of 3H-elastin/well, but appears to be dependent on the time period of AM culture. TIMP (at 5 microM, maximal dose examined) inhibited the measured elastolytic activity by 25% in 24-h cultures compared to 69% in 72-h cultures; Z-phe-phe (at 10 microM, dose at which maximal effect was obtained) inhibited the elastolytic activity by 45% in the 24-h cultures compared to 34% in the 72-h cultures. These findings indicate that differences in substrate levels and in culture time have a significant effect on the results obtained in measurement of AM-mediated elastolytic activity in culture, which may account for the conflicting reports in the literature. Thus standard optimal assay condition are required for valid interpretation of results of AM-mediated elastolytic activity measurements. PMID- 8200110 TI - A method for determination of xylose utilizing glucose dehydrogenase. AB - A method is described for xylose determination on the Ciba-Corning 550 Express that utilizes the slower enzymatic action of glucose dehydrogenase (GDH) on D xylose, after prior removal of glucose. Glucose oxidase is added to serum or urine and incubated for 120 min at 37 degrees C. After incubation, a perchloric acid filtrate of the specimen is added to the GDH reagent in the presence of NAD, the amount of NADH produced being proportional to the amount of xylose present. Absorbances at 340/380 nm are read at 180 s and 600 s after the reagent is added. The standard curve is linear to 7.50 mmol/L and the method showed day-to-day imprecision (CV%) of 2.7 (n = 18), 1.8 (n = 17), and 2.2 (n = 17) at concentrations of 0.62, 1.18, and 2.60 mmol/L, respectively. Recoveries ranged from 99 to 106% for sera and 96 to 100% for urines. Good correlation was obtained when tested against established automated ferricyanide and p-bromoaniline methods. PMID- 8200111 TI - A rapid method for measurement of ethylene glycol. AB - It has been reported that ethylene glycol produces a positive interference in the triglyceride assay on the DuPont aca discrete analyzer. The sensitivity of this method for ethylene glycol was exploited to develop a rapid and convenient method for detecting and quantitating ethylene glycol in serum by the use of a "triglyceride gap." This method is based on the difference between two different enzymatic triglyceride measurements; the DuPont aca triglyceride measurement, which uses lipase and glycerol dehydrogenase, and a Boehringer Mannheim method, which uses lipase, glycerol kinase, glycerolphosphate oxidase, and peroxidase. Serum pools were spiked with increasing concentrations of ethylene glycol to construct a standard curve (linear to 25 mmol/L). Patients specimens and control sera were analyzed using a one point calibration. Within-run and between-run coefficients of variation (CV) of 1.5, 2.8, 5.8, and 3.2%; 3.4%; and 12.6% were obtained at ethylene glycol concentrations of 20.13, 8.37, and 2.18 mmol/L, respectively. The sensitivity of this method is 1.0 mmol/L. Methanol, ethanol, n propanol, isopropanol, and acetone at 100 mmol/L; 20 mmol/L 1,3-propanediol; and 10 mmol/L glycolic acid, oxalic acid, glyoxylic acid, and lactic acid did not interfere in the quantitation of ethylene glycol. High levels (10 mmol/L) of beta hydroxybutyrate and glycerol showed a slight positive interference on the quantitation of ethylene glycol, whereas 10 mmol/L glycoaldehyde caused a substantial overestimation of serum ethylene glycol. The presence of propylene glycol, at levels ranging from 5 to 50 mmol/L, resulted in an underestimation of serum ethylene glycol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200112 TI - Investigation of rapamycin transport and uptake across absorptive human intestinal cell monolayers. AB - An in vitro intestinal cell culture model was used to characterize and investigate factors affecting uptake and transport of rapamycin (RAPA), a potent immunosuppressive drug. Studies were performed on three human intestinal cell monolayers (Caco-2, HCT-8, and T84), grown on microporous membrane inserts for 12 days. RAPA transport in all three monolayers was found to be dose dependent. The highest rates of transport were found at the highest tested final RAPA concentration of 10,000 micrograms/L. Apical to basal RAPA transport was linear in Caco-2 cell monolayers for up to 60 min, and in HCT-8 and T84 cell monolayers for up to 120 min. Temperature sensitive RAPA transport was found because incubation at 4 degrees C markedly attenuated transport by 97, 90, and 78% for Caco-2, HCT-8, and T84 monolayers, respectively. In all three monolayers RAPA transport was highly polarized because the apical to basal transport was greater than that in the opposite direction. RAPA uptake and transport across cell monolayers were compared when 10,000 micrograms/L of RAPA (cold) plus 0.05 microCi 14C-RAPA was added in combination with varying final concentrations (1,000, 10,000, and 100,000 micrograms/L) of the immunosuppressive drugs, CsA or RS. Increasing concentrations of CsA resulted in a significant dose-dependent decrease in 14C-RAPA transport across cell monolayers. In contrast, at high (100,000 micrograms/L) RS concentrations, 14C-RAPA transport was significantly increased. Uptake of 14C-RAPA into cell monolayers was significantly decreased only with the 100,000 micrograms/L CsA concentration. These studies suggest that combinations of immunosuppressive drugs given orally have a potential for altering the intestinal transport and uptake of RAPA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200113 TI - Variable selectivity of the Hitachi chemistry analyzer chloride ion-selective electrode toward interfering ions. AB - Chloride measurements by ion-selective electrodes are vulnerable to interference by anions such as iodide, thiocyanate, nitrate, and bromide. We have found that the degree of interference of these anions on the Hitachi chemistry analyzer chloride electrode varies from electrode to electrode and this variation can even occur within the same lot of membrane. This variation is not dependent upon the length of time the cartridge has been in the analyzer because no correlation existed between the usage time and the electrode response to interfering ions. Neither is this variation due to the deterioration of the electrode because all electrodes tested had calibration slopes within the manufacturer's specification. Our study, however, showed that even after repeated exposure to a plasma sample containing 2 mM thiocyanate, the chloride electrode was still able to accurately measure the chloride in plasma without thiocyanate, thus confirming that a carryover effect does not exist from a previous thiocyanate-containing sample. PMID- 8200114 TI - A comparison of cyclosporine assays using sequential samples from selected transplant patients. AB - The monitoring of cyclosporine (CsA) whole blood concentrations is an integral part of immunosuppressive treatment with this drug. Although such monitoring has been facilitated by the introduction of monoclonal immunoassay techniques, there is a paucity of published data comparing the assays longitudinally in selected patients. The purpose of our study was to co-evaluate two monoclonal immunoassays (Cyclosporine FPIA whole blood assay, Abbott Laboratories; Cyclo-Trac SP-whole blood RIA, Incstar Inc.) and a high-performance liquid chromatography (HPLC) technique for quantitating CsA in sequentially collected trough whole blood samples from 14 patients up to 75 days after renal (n = 6), heart (n = 3), and liver (n = 5) transplantation. HPLC CsA metabolite analyses (AM1, AM9, AM4N) were performed. Although CsA concentrations within most patients were significantly higher (p < 0.05, paired t test) when measured by both immunoassay techniques compared to HPLC, levels determined in three patients, (one liver, two renal) for the FPIA/HPLC comparison and one patient (liver) for the RIA/HPLC comparison were not significantly different (p > 0.05). CsA levels within nine patients were not significantly different (p > 0.05) when FPIA and RIA were compared, but results within three patients, (one liver, two renal) were significantly higher (p < 0.05) by RIA compared to FPIA, but results within one patient (heart) were significantly higher (p < 0.05) by FPIA. Our results demonstrate first that depending on the patient, HPLC-derived CsA results are not consistently lower than results generated by immunoassay techniques and second that CsA levels obtained by FPIA are statistically equivalent or in some patients, statistically less than RIA-derived levels. PMID- 8200115 TI - Human liver plasma membranes contain an enzyme activity that removes membrane anchor from alkaline phosphatase and converts it to a plasma-like form. AB - Treatment of liver plasma membranes with Triton X-100 allowed an endogenous alkaline phosphatase-converting activity to convert amphiphilic alkaline phosphatase (membrane anchor covalently attached) to hydrophilic dimers that resemble the enzyme found in normal plasma. The Triton-solubilized activity was unaffected by protease inhibitors. Amphiphilic alkaline phosphatase purified from human liver and placenta were both substrates. The Triton-solubilized enzyme would not hydrolyze L-3-phosphatidyl(2-3H)-inositol or p-nitrophenylphosphoryl choline, nor would it cleave endogenous alkaline phosphatase from intact plasma membranes. These observations and the analysis of the protein product of the hydrolysis of placental alkaline phosphatase, following treatment with the converting activity, indicated that the enzyme has the specificity of a glycosyl phosphatidylinositol phospholipase D. Further characterization of the enzyme activity suggests additional similarities with the glycosyl-phosphatidylinositol phospholipase D found in mammalian plasma. Alkaline phosphatase-converting activity in plasma membranes represented the same percent of total protein as it did in whole liver, whereas serum contained 3- to 10-times this amount. Endogenous converting activity in plasma membranes was not solubilized by salt washes, sonication, or repeated freeze-thaw treatments. We believe it is unlikely that the alkaline phosphatase-converting activity in liver plasma membranes resulted from adsorption of the enzyme present in plasma. PMID- 8200116 TI - High allele frequency of apolipoprotein(a) phenotype LpS4 is associated with low serum Lp(a) concentrations in Koreans. AB - We determined apo(a) phenotypes using SDS-PAGE followed by immunoblotting in samples from a control group of 179 and from 68 Korean patients with coronary artery disease (CAD). The CAD group showed significantly higher Lp(a) levels than the control group, which might be partially attributable to the differences in apo(a) phenotype frequencies although it was not statistically significant, and was partially attributable to the significant difference in Lp(a) levels of S2 or null phenotypes between the two groups. The apo(a) allele frequencies between ethnic groups already reported (Austrians, American blacks, Japanese, and Koreans), were compared by the Chi-square test. In the Korean population, the apo(a) allele frequencies demonstrated a high frequency of the LpS4 allele associated with a low Lp(a) concentration. This result suggests that the concentration and allele frequency of Lp(a) might be one of the factors in explaining the low incidence of CAD in the Korean population. PMID- 8200117 TI - Changes in cholesteryl ester transfer protein activity during normal gestation and postpartum. AB - Cholesteryl ester transfer protein (CETP) activity was measured in a d > 1.21 kg/L plasma fraction collected from healthy women at different times during gestation, postpartum, and in control women. CETP activity was highest in the second trimester of gestation, declined at the third trimester, and was lowest at postpartum. Only the value at the second trimester was significantly different from that of control women. This trend differed from that of circulating lipoproteins: very low-density lipoprotein (VLDL)-lipids, including triglycerides and cholesterol, increased progressively from the first to the third trimester, and then declined at postpartum. Low-density lipoprotein (LDL)-cholesterol levels, like VLDL levels, rose during gestation but then remained elevated at postpartum. High-density lipoprotein (HDL)-cholesterol as well as HDL phospholipids and apolipoprotein A-I, peaked in the second trimester, remaining elevated in the third trimester and then fell at postpartum. Finally, HDL triglyceride increased markedly from the first to the second trimester, rose somewhat higher during the third trimester, and declined at postpartum. When all the samples from pregnant women were considered together, CETP activity correlated significantly with HDL-triglyceride levels and the changes in CETP activity during gestation and postpartum paralleled those of the HDL triglyceride/VLDL-triglyceride ratio. These results suggest that CETP contributes to the exaggerated accumulation of triglycerides in HDL that begins in the second trimester of human gestation. PMID- 8200118 TI - Thyrotoxicosis and hungry bone syndrome--a cause of posttreatment hypocalcemia. AB - We report a case of a 54 year old woman with a history of recurrent Graves' disease, treated previously by thyroidectomy and later by radioiodine, who subsequently presented with tetany. Laboratory results revealed a profound hypocalcemia (total calcium 1.00 mmol/L; ionized calcium 0.53 mmol/L) and hyperphosphatemia (2.66 mmol/L) with low levels of parathyroid hormone. Although the patient's symptoms resolved after 5 days of treatment, hypocalcemia and elevated serum levels of bone-specific alkaline phosphatase (ALP, EC 3.1.3.1) activity and skeletal muscle isoenzyme (CK-MM) creatine kinase (EC 2.7.3.2) activity persisted to her discharge, 3 weeks later. Attention is drawn to the recognition and management of recalcification tetany due to the "Hungry (for calcium) Bone Syndrome," a biochemical and hormonal disturbance of calcium homeostasis and bone metabolism in the posttherapy thyrotoxic patient with hypoparathyroidism. This condition can be monitored by the use of calcium profile investigations, including bone-specific ALP, in addition to routine laboratory tests of thyroid function. PMID- 8200119 TI - Discrepancies between lipoprotein(a) concentrations in icteric sera measured by immunonephelometry and electroimmunodiffusion. AB - We compared the lipoprotein(a) [Lp(a)] levels in 32 icteric sera determined both by an electroimmunodiffusion assay (EIA), using the Hydragel Lp(a) kit (Sebia, France) and by two immunonephelometric assays, one on a Behring Nephelometer Analyzer (BNA), using antiserum from immunofrance, and the other on a Beckman analyzer (Array), using antiserum from Dako (Denmark). With the EIA assay, the Lp(a) level was 0.09 +/- 0.09 (mean +/- SD in g/L), with the BNA assay, 1.01 +/- 1.51 and with the Array assay, 0.05 +/- 0.05. Sample blanks values (0.76 +/- 1.28 g/L) demonstrated that the high Lp(a) levels obtained in the BNA assay are caused by nonspecific precipitation. Analysis of the precipitate indicated the presence of Lipoprotein X, an abnormal lipoprotein that appears in the serum of patients with obstructive jaundice or with lecithin-cholesterol acyltransferase deficiency. The precipitant seems to be polyethyleneglycol (PEG) that was added to the reaction medium in both the BNA and the Array assays to stabilize the Lp(a)-anti Lp(a) immune complex. In the Array assay, interference by this nonspecific precipitation is eliminated by preliminary centrifugation of the diluted sample. However, coprecipitation of Lp(a) could occur during this step. Consequently, the results of Lp(a) measurement in serum from patients with hepatobiliary diseases should be interpreted with caution when immunonephelometric assays are used with a medium containing PEG. PMID- 8200120 TI - Mechanisms of small intestinal adaptation. AB - Luminal nutrition, hormonal factors and pancreaticobiliary secretions are probably the major mediators of small intestinal adaptation. Their actions, as discussed in this paper, are likely to be interrelated. Direct local enterotrophic effects cannot account for all the actions of luminal nutrients. Additionally, hormonal factors have been shown to contribute to indirect effects of luminal nutrients and enteroglucagon is a likely mediator of adaptive responses. Furthermore, epidermal growth factor is a peptide for which there is convincing evidence of an enterotrophic action. Attention is drawn to the fact that pancreaticobiliary secretions may have a physiological role in stimulating small intestinal mucosal proliferation. Other factors may also influence small intestinal mucosal proliferation (e.g. prostaglandins, neurovascular mechanisms, bacteria). Additionally, polyamines are crucial in initiating cell division in the small intestine, but the detailed mechanisms of their action require further clarification. Finally, a number of therapeutic applications of small intestinal epithelial cell proliferation are discussed. PMID- 8200122 TI - Nitric oxide: an ubiquitous actor in the gastrointestinal tract. AB - The digestive system is one of the major sources of nitric oxide, which, due to its smooth muscle-relaxing and vasodilating properties, appears to play a key role in the regulation of gastrointestinal motility, mucosal blood flow and gastroprotection. In addition nitric oxide takes part in the control of pancreatic secretion and liver functions. Recent studies suggest that the substance may be involved in the pathogenesis of achalasia, toxic megacolon, Hirschsprung's disease and portal hypertension. PMID- 8200121 TI - Diamine oxidase: an overview of historical, biochemical and functional aspects. AB - This article is a review of the historical, biochemical, and functional aspects of the enzyme diamine oxidase (DAO). The amine oxidase DAO, formerly called histaminase, is found in various tissues, but is especially active in the intestinal mucosa. Its function is the oxidative deaminating of several polyamines, essential substances for cell proliferation. DAO is thus a regulating enzyme in rapidly proliferating tissues such a bone marrow and intestinal mucosa. Results from several studies have demonstrated that both ornithine decarboxylase (ODC) and DAO activity rise during adaptive hyperplasia seen after small bowel resection. The ODC-dependent increase in polyamine content and subsequent increase in cell proliferative activity is probably downregulated locally in the villus tip by the increased DAO activity. DAO is normally present in very small amounts in the circulation and its basal plasma levels are positively correlated with the maturity and integrity of the intestinal mucosa. After intravenous administration of heparin, DAO is released from its capillary binding sites in the lamina propria into the peripheral circulation. Measurement of postheparin DAO release enhances its sensitivity and is now extensively studied to assess its value as follow-up or screening test for several enteropathies. Measuring basal as well as postheparin DAO levels has potential relevance following small bowel transplantation. Rejection of the small bowel graft leads to mucosal damage, which could conceivably lead to changes in DAO activity. PMID- 8200123 TI - Cytoprotection with misoprostol: use in the treatment and prevention of ulcers. AB - Prostaglandins protect the gastric mucosa by decreasing gastric acid secretion, increasing mucus and bicarbonate production and maintaining mucosal blood flow. Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastroduodenal damage and this is due, at least in part, to inhibition of mucosal prostaglandin production. Misoprostol is a synthetic analogue of prostaglandin E1 which has been used in the healing of ulcers and prevention of peptic ulcers in patients taking NSAIDs. Misoprostol is of equal efficacy to H2 antagonists in the healing of ordinary peptic ulcers (not associated with NSAIDs). Misoprostol is superior to placebo in healing NSAID ulcers during continued NSAID treatment but there have been no comparative trials with other ulcer-healing drugs. Misoprostol, H2 antagonists and sucralfate are of similar efficacy in prevention of NSAID-associated duodenal ulcers but misoprostol is more effective in prevention of gastric ulcers. Misoprostol has not been compared to omeprazole in this situation. PMID- 8200124 TI - Chronic refractory diarrhoea: a manifestation of endocrine disorders. AB - Hormonally mediated chronic refractory diarrhoeas constitute a rare but important group which often defy precise diagnosis when conventional routine diagnostic methods are used. Hormonal diarrhoea may occur in carcinoid syndrome, medullary carcinoma of the thyroid, thyrotoxicosis, gastrinoma, VIPoma, glucagonoma, somatostatinoma and systemic mastocytosis. Diagnosis of these conditions depends upon the awareness of clinicians, on clinical features and on documentations of high circulating hormones, if required, by using provocative tests. Precise localization of the tumours may be accomplished by ultrasonography, computerised axial tomography, angiography, percutaneous transhepatic portal and pancreatic venous sampling for the estimation of hormone concentrations. Benign tumours are removed surgically. Malignant neoplasms are treated either by surgery or chemotherapy depending upon the progress of the disease. Diarrhoea usually ceases when hormone levels are normalized following successful treatment. PMID- 8200125 TI - Treatment of external biliary, pancreatic and intestinal fistulas with a somatostatin analog. AB - Somatostatin and its long-acting analog octreotide (SMS 201-995) inhibit several gastrointestinal functions. Their effects have been studied in the treatment of small numbers of external pancreatic, intestinal and biliary fistulas. We treated 8 biliary, 4 pancreatic and 5 intestinal cutaneous fistulas with octreotide. Mean decreases in fistula output before octreotide treatment were not significant (p > 0.01 for each group). On the 1st day of octreotide treatment, mean fistula output decreased from 412 +/- 60.4 to 234 +/- 57.7 ml in the biliary, from 457.5 +/- 57.5 to 217.5 +/- 11.8 ml in the pancreatic and from 564 +/- 49.2 to 217.5 +/- 11.8 ml in the enterocutaneous fistula groups (p < 0.01 for each). No serious side effects were recorded. We conclude that octreotide is an important adjunct in the conservative treatment of external biliary, pancreatic and intestinal fistulas, by decreasing their output. PMID- 8200126 TI - The long-standing quest for tumor rejection antigens. AB - Several tumor antigens recognized by T lymphocytes have now been identified at the molecular level. Different mechanisms could account for their expression: activation of normally silent genes, point mutations in normally expressed genes, chromosomal translocations generating combinatorial epitopes, or post translational modifications of proteins. A major consequence of these results is the notion that potential tumor rejection antigens are often shared by a significant proportion of human tumors. This may have important implications in cancer immunotherapy, especially since tumors expressing a defined antigen can be identified clinically on the basis of the expression of the relevant gene. PMID- 8200127 TI - Immunobiology of Epstein-Barr virus-associated lymphomas. PMID- 8200128 TI - Tumor-specific immune responses and opportunities for tumor vaccines. PMID- 8200129 TI - Concluding comments: immunologic intervention in therapy of cancer. PMID- 8200130 TI - Induction of graft versus host disease in SCID mice by MRL/lpr cell transfer. AB - We have investigated the graft versus host (GvH) disease induced in immunodeficient SCID (H-2d) mice by intravenous (iv) or intraperitoneal (ip) transfer of either spleen or lymph node cells from autoimmune (MRL/lpr and MRL/++ mice, H-2k) and normal (CBA, H-2k) mice. Rapid and lethal GvH disease was observed when cells from MRL/lpr or MRL/++ were iv transferred into SCID mice, while spleen cells from nonautoimmune CBA donors were partially tolerized into SCID recipients and induced only lower levels of GvH reaction. No GvH reaction (complete tolerance) was observed when CBA lymph node cells were iv transferred into SCID recipients. In contrast, the ip injection of MRL/lpr or CBA spleen cells induces similar levels of GvH. The development of GvH disease in SCID recipients was due to the expansion of alloreactive CD8+ cells displaying significant cytotoxic activity against H-2d, but not against autologous targets. Also, a significant decrease of CD4/CD8 ratio was observed in the course of GvH caused by the iv transfer of cells from MRL/lpr mice. Altogether, these data support the hypothesis that lymphocytes from the MRL/lpr mice may escape tolerance in the GvH reaction. PMID- 8200131 TI - Long-term humoral and cellular immunity after vaccination with cell culture rabies vaccines in man. AB - To determine the duration of anti-rabies immunity, peripheral blood of 18 vaccinees was obtained between 2 and 14 years after immunization. Peripheral blood mononuclear cells (PBMC) and serum were tested for the presence of either rabies virus-specific antibodies or rabies antigen-specific proliferation. Neutralizing immunoglobulin class G anti-rabies virus antibodies could be detected in sera of all vaccinees, but not in 18 age- and sex-matched controls. Rabies antigen-induced proliferation of PBMCs from vaccinees was significantly higher than that of controls. The anti-rabies T and B cell response showed no time-dependent pattern. These results suggest the induction of a long-term immunity after rabies immunization according to pre- and post-exposure schedules with inactivated cell culture vaccines against rabies. PMID- 8200132 TI - Dietary Platycladus orientalis seed oil suppresses anti-erythrocyte autoantibodies and prolongs survival of NZB mice. AB - Dietary fish oils rich in 20:5(5,8,11,14,17) and 22:6(4,7,10,13,16,19) are known to replace arachidonic acid [20:4(5,8,11,14)] and to improve the immunopathology of New Zealand mice. However, in humans, similar dietary strategies may be impractical because of the high levels of fish oils required. In contrast, we believe that beneficial effects in humans may be attainable using new exotic fatty acids. Toward this end, we have focused on 5,11,14-eicosatrienoic acid [5,11,14-ETA, 20:3(5,11,14)]. This fatty acid is structurally analogous to 20:4(5,8,11,14) but lacks the delta-8 double bond essential for conversion to eicosanoids. To examine our hypothesis, diets containing the oil of Platycladus orientalis containing 3% 5,11,14-ETA, a matched control oil, fish oil, or safflower oil were fed to NZB mice. There was a dramatic delay in both the onset and the titer of direct Coombs' tests in mice fed P. orientalis oil. These were directly reflected by the abundance of 5,11,14-ETA in serum lipids. Most striking was the accumulation of 5,11,14-ETA in serum and tissue phospholipids. Though constituting only 3% of dietary fatty acids, 5,11,14-ETA was the most abundant long chain polyunsaturated fatty acid in the serum phospholipids, suggesting that it very successfully competed with 20:4 as a constituent of membrane lipids. 5,11,14-ETA was incorporated into all tissue phospholipids examined except brain phosphatidyl inositol. Among tissues, liver showed the highest incorporation of 5,11,14-ETA into phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylinositol (PI), yet spleen PE had a higher quantity of ETA than other tissues. Lesser arachidonate in spleen PS, heart PC, and heart PI showed the evidence of replacement by 5,11,14-ETA. The data presented illustrates how new nutrition can modify autoimmune responses and emphasizes the need for further studies based on new nutritional strategies. PMID- 8200133 TI - Structural and functional similarities between synthetic HIV gp41 peptides and defensins. AB - Synthetic peptides derived from the putative immunosuppressive region of HIV-1 gp41 were examined to identify the amino acids required for suppressive activity. The active sequence was similar to the pseudosubstrate regulatory peptide of protein kinase C and to a sequence from the cyclic immune peptides known as defensins. The activity of the gp41 peptides appeared to be dependent upon a structural conformation, possibly a looped motif like that found in defensins. This similarity to defensins, which can insert themselves into lipid bilayers, was further strengthened by demonstrating that gp41 peptides have the ability to associate with liposomes and lymphocyte membranes. These results suggest that the immunosuppressive region of gp41 may participate in the membrane interactions required for viral fusion and infectivity. PMID- 8200134 TI - Inhibition with N-acetylcysteine of enhanced production of tumor necrosis factor in streptozotocin-induced diabetic rats. AB - We previously reported that the in vivo production of the tumor necrosis factor alpha (TNF) was significantly enhanced after the onset of diabetes in spontaneous type 1 and 2 diabetic animals. In this report we confirmed the enhanced production of TNF in streptozotocin (STZ)-induced diabetes and then attempted to suppress the enhanced TNF production with N-acetylcysteine (NAC), a precursor of glutathione synthesis. The lipopolysaccharide-induced serum TNF activities were significantly enhanced in STZ-induced diabetic rats (6-18 weeks of age) compared with those of nondiabetic rats throughout the 12-week experiment. A single, oral administration of NAC (200 or 1000 mg/kg body wt) significantly suppressed the enhanced TNF production in the diabetic rats compared with that in untreated rats in a dose-dependent manner. On the other hand, in the long-term (6 or 12 weeks) administrations, smaller doses of NAC (50 or 200 mg/kg/day) also significantly inhibited the enhanced production of TNF regardless of the dose of NAC. NAC administration, however, did not suppress the TNF production of nondiabetic rats. The long-term NAC administration affected neither body weight nor levels of serum glucose, fructosamine, albumin, and triglyceride. These results show that NAC administration significantly suppressed the enhanced TNF production in diabetic rats and indicate that NAC might be useful in preventing TNF-mediated pathological conditions in diabetes. PMID- 8200136 TI - [Ictal electroencephalographic findings and clinical seizure types in postencephalitic epilepsy]. AB - A prolonged video/electroencephalogram (EEG) monitoring was performed in two patients with intractable epilepsy after adult onset acute encephalitis. Clinically both patients were thought to have a localized epileptogenic focus because of the single stereotyped clinical seizures by history in two patients, and a well localized lesion shown by MRI in one patient. The video/EEG monitoring, however, revealed multiple EEG foci ictally as well as interictally in both patients. Moreover, both patients were found to have at least two different patterns of clinical seizures. In patients with adult onset postencephalitic epilepsy, therefore, it is necessary and important to evaluate enough number of seizures by prolonged video/EEG monitoring even if seizures are clinically stereotyped by history and localized lesions are present on brain imaging. PMID- 8200135 TI - Hyperprolactinemia in male NZB/NZW (B/W) F1 mice: accelerated autoimmune disease with normal circulating testosterone. AB - It has been proposed that the immunostimulatory hormone, prolactin, is associated with flares of systemic lupus erythematosus (SLE). In autoimmune female NZB/NZW F1 (B/W) mice with accelerated lupus-like disease, hyperprolactinemia accelerated autoimmunity. The current study explored effects of moderate and severe hyperprolactinemia in male B/W mice, which have late-onset SLE. Autoimmune disease in B/W males was assessed by measurement of anti-DNA antibodies (anti DNA), gp70-anti-gp70 immune complexes (gp70IC), IgM, IgG, and renal function. Serum testosterone concentrations were assayed serially. All mice were necropsied when moribund. Hyperprolactinemic B/W males were characterized by premature appearance of anti-DNA and gp70IC and elevation of IgM and IgG. Hyperprolactinemia accelerated mortality with vasculitis and renal disease compared to control mice. Serum testosterone concentrations were not suppressed. In male B/W mice, chronic hyperprolactinemia stimulated autoimmune disease activity; the deleterious effects of prolactin were not mediated through suppression of the immunoprotective hormone, testosterone. This observation supports the proposed association between elevated prolactin levels and exacerbations of SLE. PMID- 8200137 TI - [Analysis of dysarthria in amyotrophic lateral sclerosis--MRI of the tongue and formant analysis of vowels]. AB - To evaluate dysarthria in patients with ALS, we used MRI (gradient rephasing echo method) and compared it with the computed acoustic analysis. Five ALS male patients of progressive bulbar palsy type and five normal male were asked to phonate the five Japanese vowels, /a/./i/./u/./e/./o/. MRI of the sagittal tongue and vocal tract was obtained by the gradient rephasing echo method (0.2 Tesla, TR:30 ms, TE:10 ms, FA 25 degrees C, Hitachi). We could clearly visualize the change of tongue shape and the narrow site of the vocal tract for each vowel phonation. In normal subjects, the tongue shape and the narrow site of the vocal tract were distinguishable between each vowel, but unclear in ALS. Acoustic analysis showed that the first formant frequency of /i/./u/ in ALS was higher than normal and the second formant frequency of /i/./e/ in ALS was significantly lower than normal. The discrepancy from the normal first, second and third formant frequency for each vowel of ALS was most seen in /i/./e/. It was speculated that /i/ and /e/ were the most disturbed vowels in ALS. The first and second formant frequency of vowel depends on the tongue shape and the width of the oral cavity. Therefore the results of the acoustic analysis in ALS indicated poor movement of tongue in /i/./u/./e/ and were compatible with the findings of the sagittal tongue MRI. The sagittal view of the tongue in the gradient rephasing echo MRI and the acoustic analysis are useful in evaluation dysarthria in ALS. PMID- 8200138 TI - [Effect of physostigmine on acetylcholine and monoamine metabolites in rat frontal cortex with lesions of the nucleus basalis of Meynert]. AB - Acetylcholine (ACh) and monamine (MA) metabolites were collected from the frontal cortex of free moving rats, using a microdialysis technique. In rats subjected to bilateral ibotenic acid lesioning of the nucleus basalis of Meynert (nbM), ACh release was markedly decreased, while DOPAC, HVA and 5-HIAA were not affected. Physostigmine (0.3 mg/kg, IP) increased ACh concentration in the brain dialysate, and the rate of ACh increase was lower in nbM-lesioned rats than that in unoperated rats. Physostigmine also increased the concentration of MA metabolites in both nbM-lesioned and unoperated rats equally. The results indicate that there may be some interaction between non nbM-originated cholinergic systems and monoaminergic systems in the frontal cortex. PMID- 8200139 TI - [Magnetic resonance imaging of spinal cord lesions in 22 multiple sclerosis patients]. AB - We reviewed MRI findings in 22 patients (37 cases) with clinically diagnosed multiple sclerosis (MS) with spinal cord lesions. The spinal cord lesions were detected in 17 (46%) of these 37 cases on MRI. The cervical cord lesions were more detectable than other spinal cord lesions. At the thoracic level, the upper lesions were more detectable than the lower ones. In this study, no correlation was found between the disease duration, the rate of functional disturbance and the detectable rate of spinal cord lesions. The characteristic findings of the lesions were swelling and the enhancement effect of Gd-DTPA in the patient group with a disease duration of less than three years, and atrophic change in the patient group with a disease duration of greater than seven years. The period of the enhancement effect of Gd-DTPA varied in each case, and it may reflect the clinical course. Syrinx-like lesions were found in four cases. In one of them, atrophic change was found in the same region six months after the follow up study. Although the precise reason for the syrinx-like lesion was unclear, a relationship between syrinx-like lesion and atrophy of the spinal cord was suggested. The MRI findings of the spinal cord lesions in MS varied in each case and in each stage of the disease. PMID- 8200140 TI - [Pretectal syndrome caused by a plaque of multiple sclerosis]. AB - We report a 20-year-old woman who presented with pretectal syndrome. She was well until September 12, 1991 when she noted an onset of difficulty in focusing her eyes. On neurologic examination, she showed convergence-retraction nystagmus and restriction of vertical eye movements more in the upward direction. A cranial CT scan revealed no abnormality. An oligoclonal band was detected in CSF. An MRI using Hitachi MRH-500 (0.5 T) revealed an abnormal high signal intensity lesion at the ventral area of the midbrain aqueduct, and another small lesion in the temporal white matter on the left. In addition, periventricular scattered small lesions were also visualized. Hydrocephalus, tumors and cerebrovascular disorders are common causes of pretectal syndrome, but multiple sclerosis is a rare one. Problems associated with the similar terminologies including Parinaud's syndrome, sylvian aqueduct syndrome or dorsal midbrain syndrome were discussed. According to Ranalli (1988), fibers mediating the upward gaze originate in the rostral interstitial MLF (riMLF), cross through the posterior commissure, and terminate in the contralateral oculomotor complex. On the other hand, downward gaze fibers take another route to the oculomotor complex. This may be a reason for the dissociation of the upward and downward gaze palsy, and the riMLF seems to be one of the most important structures responsible for the upward gaze. PMID- 8200141 TI - [A case of cortical blindness confirmed by single photon emission computerized tomography and visual evoked potential]. AB - We reported a rare case of cortical blindness in cerebral ischemia following post anoxic state confirmed by single photon emission computerized tomography (SPECT) and visual evoked potential. A 45-year-old woman who had been suffering from bronchial asthma was admitted to our hospital because of sudden progressive dyspnea and depressed consciousness. When she arrived at the hospital by ambulance, she was in hypoxic state and fell into cardiac arrest. Her respiratory condition gradually improved with respirator assistance, and she recovered consciousness, but complained of bilateral visual loss. She had no history of any neurological or psychiatric illness, nor of drug abuse. On neurological examination, she was alert and oriented. Light reflex, optic fundi, extraocular movement and other neurological findings were all normal, with the exception of bilateral blindness. EEG showed generalized slow background activity, but cranial CT scan and MRI showed no abnormalities. 99mTc-HMPAO SPECT indicated hypoperfusion in prominent bilateral occipital and parietal lobes. Simultaneous recordings of pattern reversal visual evoked potential (VEP) and electroretinograms (ERG) using transient checkerboard pattern reversal in 15 min and 30 min checks were recorded. The results showed normal b waves but absent P100 in the bilateral eyes. From the patient's neurological symptoms and the results of SPECT and VEP, she was diagnosed as cortical blindness in post-anoxic state. On the 30th hospital day, her visual acuity and visual fields improved, but she was suspected of having visual agnosia. Eighty-five days after the onset of the neurological abnormalities, no traces of visual disturbances were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200142 TI - [A case of chronic herpes encephalitis with myelodysplastic syndrome (MDS)]. AB - A 72-year-old male suffering with MDS was admitted to our hospital because of slowly progressive dementia, convulsions and consciousness disturbance. A CT scan of the brain showed a low density area in the right temporal to parietal lobe and T2-weighted MRI of the brain revealed a high intensity signal in the same area. Herpes simplex virus DNA was detected in CSF by PCR method. He was diagnosed as having herpes simplex encephalitis but his clinical course was prolonged and considered atypical as herpetic infection in CNS. However, after administration of aciclovir, progression of his symptoms stopped, and a CT scan still revealed abnormal findings with the same area after more than four months. We thought his chronic course of herpes encephalitis was caused by incomplete immune function suppressed by MDS. PMID- 8200143 TI - [Syndrome of contracture facio-brachio-abdomino-crurale en flexion in a case of isolated ACTH deficiency--biopsy findings of muscle and nerve]. AB - A 55-year-old woman presented with a one-year history of painful muscle cramps and progressive flexion contractures of the arms, pelvic girdles and knees. Laboratory evaluation was summarized as follows: low plasma cortisol and ACTH levels, delayed response of plasma cortisol to ACTH administration, no response of plasma ACTH level to insulin administration, and normal plasma LH, FSH, GH, TSH and PRL levels. She was diagnosed as isolated ACTH deficiency. EMG was silent in contractured muscles at rest. Biopsy of the biceps femoris muscle revealed a marked reduction in fiber size, type 2 fiber atrophy and type 1 fiber predominance. The nerve conduction velocities of the peripheral nerves were found to be decreased. The biopsied specimen of the sural nerve revealed a loss of large myelinated fibers and segmental demyelination. Both flexion contractures and nerve conduction velocities were gradually improved with the replacement of hydrocortisone. PMID- 8200144 TI - [Slow-upward ocular bobbing in a patient with striatonigral degeneration]. AB - We herein report a patient with the abnormal eye movement characterized by a conjugate slow-upward eye movement followed by a fast-downward movement to the primary position (slow-upward ocular bobbing). A 55-year-old man with a 12 years' history of striatonigral degeneration developed pneumonia and was admitted to our hospital. In addition to the parkinsonian features like akinesia and rigidity, examination revealed slow-upward ocular bobbing. There were no accompanying ocular abnormalities. This spontaneous eye movement was recognized throughout his stay in the hospital, irrespective of his consciousness level. Although other forms of ocular bobbing/dipping are usually associated with the loss of consciousness, all three reported patients with this slow-upward ocular bobbing were awake and responsive, therefore, suggesting a different kind of background pathophysiology in this unique eye sign. PMID- 8200145 TI - [Leber's hereditary optic neuropathy with onset at the age of 54 years]. AB - We report a 55-year-old Japanese man who had an onset of bilateral progressive blurring of vision at age 54 years. His younger sister had diminished visual acuity since 14 years of age. On neurologic examination, bilateral optic atrophy was present. He could only count the digit numbers at 40 cm-distance with his right eye, and the visual acuity of the left eye was 0.08. Otherwise, neurologic examination was unremarkable. The PCR analysis of mitochondrial DNA prepared from whole blood revealed a G to A mutation at the nucleotide 11,778; the so-called Wallace's mutation. He was diagnosed as Leber's hereditary optic neuropathy. It is rare to see a patient with LHON with the onset after 50 years of age. PMID- 8200147 TI - [Gastric acid secretion and absorption of levodopa in patients with Parkinson's disease--the effect of supplement therapy to gastric acid]. AB - Since an oral regimen of levodopa has been instituted for treatment of Parkinson's disease, its absorption and metabolism has been well demonstrated. However, its chemical characteristics of high solubility in acid solution and low solubility in water have not been well known. We paid attention to this characteristic and studied the relationship between its absorption and gastric acid secretion in 38 patients with Parkinson's disease who became refractory to therapy of levodopa. We measured the pH and amount of collected fasting gastric juice. Gastric acid secretion was decreased in 22 patients (58%). In ten of these 22 patients, 30 ml of lemon juice was prescribed in every administration of levodopa as a supplement to gastric acid for two weeks. Increases of L-dopa concentration after 60 min. and 180 min. were observed after lemon juice supplement therapy. Among the Parkinson symptoms, rigidity, akinesia, and small step gait were improved in every case except one patient who showed decrease of L dopa concentration at 180 minutes. However, improvement of tremor was less remarkable. We consider this supplement therapy to gastric acid is one of the effective and useful methods in the management of Parkinson's disease. PMID- 8200146 TI - [A case of superficial hemosiderosis of the central nervous system with normal CSF findings and unknown source of bleeding]. AB - A 65-year-old woman had suffered from slowly progressive hearing loss for one year. She had neither repeated episodes of headache or vomiting nor a past history of neurosurgical operation. Neurologic examination revealed moderate diminution in hearing, pyramidal tract sign and cerebellar ataxia without dementia. CSF was under normal pressure, clear and colorless, with total protein 35 mg/dl, glucose 59 mg/dl and a cell count of 2 WBC/mm3. T2-weighted images (TR200/TE80) of high-field MRI demonstrated marginal hypointensity of the brainstem, the Sylvian fissures and the entire spinal cord. Angiography of the cerebral vessels failed to identify the source of bleeding. To our knowledge, this is the first report of superficial hemosiderosis of the central nervous system with normal CSF findings and an unknown source of bleeding confirmed by MRI. PMID- 8200148 TI - [Some consideration about cerebellar ataxia and crossed cerebellar diaschisis in Dejerine-Roussy syndrome]. AB - We report a 68-year-old right-handed male who exhibited Dejerine-Roussy syndrome including a persistent cerebellar ataxia following the left thalamic hemorrhage with special reference to the evolution of crossed cerebellar diaschisis (CCD) measured with positron emission tomography (PET). The initial PET studies performed 50 days after onset revealed a mild reduction of blood flow and glucose metabolism in the right cerebellar hemisphere in addition to the severe reduction in the left thalamus. Even in the chronic stage when the motor weakness almost disappeared, he persistently showed a cerebellar ataxia in his right extremities. The cerebellar blood flow and metabolism became normalized without laterality in the follow-up PET studies which were performed 29 months after onset, although the left thalamus and left cerebral cortices were still severely involved. The cerebellar ataxia with preserved cerebellar blood flow and metabolism following the thalamic hemorrhage was possibly associated with damage to the efferent fibers from the cerebellum, whereas the CCD observed in the early stage probably was caused by a transient involvement of the cortico-ponto-cerebellar tract at the level of the internal capsule. PMID- 8200150 TI - [Responsible lesion for diagnostic dyspraxia]. PMID- 8200149 TI - [Distribution of androgen receptors in bulbo-spinal muscular atrophy]. AB - Immunohistochemical staining with anti-androgen receptor (AR) antibody was performed in skeletal muscle specimens obtained from 3 cases with bulbo-spinal muscular atrophy (BSMA) and 12 cases with other neuromuscular disease. Anti-AR antibody staining was found exclusively in the muscle nuclei of Type 2A fibers in all of the 3 cases. But there was no positive staining in the muscle nuclei of other disease. As above mentioned, very specific immuno-staining of AR in skeletal muscle would be of benefit to diagnosis of BSMA in addition to identification of a mutation of AR gene. PMID- 8200151 TI - Adolescent sexuality: Part 4. The practitioner's role. AB - Practitioners who provide care for adolescents have a unique opportunity to address issues of adolescent sexuality. This article discusses shortcomings in residency training and possible solutions. The role of the practitioner in the office setting, issues of confidentiality and consent, and school-based sexuality education are reviewed. PMID- 8200152 TI - Postdural puncture headache in children. Etiology and treatment. PMID- 8200153 TI - Gonococcal conjunctivitis in adolescents. Recognition and management. PMID- 8200154 TI - Gross motor development of a 7-year-old girl with trisomy 18. PMID- 8200155 TI - Lesch-Nyhan syndrome in two brothers: why early diagnosis is essential. PMID- 8200156 TI - Embolization of a percutaneous central venous catheter. PMID- 8200157 TI - Pneumocephalus and exophthalmos secondary to acute sinusitis and nasopharyngeal oxygen catheter. PMID- 8200158 TI - A prospective evaluation of pediatric patients with syncope. AB - Fifty-eight children with syncope were evaluated prospectively to determine the characteristics of syncope in the pediatric age group and the yield of various diagnostic tests. The age at first syncope ranged from 0.5 to 15 years. Twenty five children presented after a single episode and 33 after multiple episodes. Ten had a history of breath-holding spells. Nineteen had a family history of syncope. A diagnosis was established in 53 patients (91%): vasodepressor (31), cardioinhibitory (13), tussive (3), hyperventilation (2), and mixed syncope (4). In five patients (9%), the cause remained unknown. The diagnosis was established from the history in 45 cases, by a positive oculocardiac reflex in 11, and by the head-up tilt test in four. We conclude that the cause of most cases of pediatric syncope is vasodepressor or cardioinhibitory and can be diagnosed by good history taking. Costly evaluations are rarely necessary. PMID- 8200159 TI - Yield of reticulocyte counts and blood smears in term infants. AB - Reticulocyte counts and blood smears are commonly recommended to evaluate jaundice in newborns. To investigate the results and diagnostic yield of these tests, we reviewed a computerized database and medical records of term newborns who had reticulocyte counts (n = 799) or blood smears (n = 781) within the first week after birth at two hospitals. Nearly a threefold difference was noted in reticulocyte counts between the two hospitals (median 8.0% vs 2.8%; P < .0001), apparently due to differences in laboratory methods. Among the patients with "abnormal" reticulocyte counts or blood smears (n = 192), isoimmunization was diagnosed in 54, presumed hemolysis of unknown etiology in two, G6PD deficiency in one, and pyropoikilocytosis in one. We conclude that better standardization of reticulocyte counts is needed. When ordered as screening tests for hemolysis in jaundiced infants, reticulocyte counts and blood smears seldom lead to diagnoses of hemolysis other than isoimmunization. PMID- 8200160 TI - Psychological aspects of parenting critically ill neonates. AB - This study was designed to objectively examine depression and distress levels in parents of ill versus parents of healthy neonates by utilizing two well-validated questionnaires, the Beck Depression Inventory (BDI) and Kellner Symptom Questionnaire (KSQ). In addition, morbidity of infants was assessed by the Minde Whitelaw Neonatal Morbidity Scale, and parents completed a socioeconomic questionnaire. Analysis of mean BDI and KSQ scores revealed significant differences between parents of ill neonates and parents of healthy neonates in BDI, total KSQ scores, KSQ anxiety, and depression scale scores. Within these groups, respondents whose scores fell into moderate to severe ranges of distress on either questionnaire were referred for counseling. The BDI and KSQ can be tools for better understanding about distress levels in parents of ill and healthy neonates. PMID- 8200161 TI - Selection of patients for management of attention deficit hyperactivity disorder in a private practice setting. AB - Attention deficit hyperactivity disorder (ADHD) is a syndrome characterized by age-inappropriate levels of motor activity, impulsivity, and inattention. A system of triage was developed to select an ADHD patient population which was manageable in a private practice setting. Seventy-four subjects with symptoms suggestive of ADHD were evaluated and diagnosed with ADHD and followed for 2 years. All subjects included in the study were shown a teaching videotape, received a full physical examination, and were counseled for approximately 1 hour. The diagnosis of ADHD was made based on the presence of eight of 14 criteria described in DSM-III, elevated Connors Rating Scale (CRS) scores, physical examination, observation, and historical information. A treatment plan involving behavioral therapy and medication was implemented with frequent follow up. Ninety-six percent of the patients showed improvement in behavior (parental report and decreased CRS scores) and/or grades (one letter grade in two classes for 12 weeks). Fifteen percent of the treated subjects were suspected of having coexistent disorders and 4% did not respond to treatment. By implementing a simple triage system and protocol for diagnosis, treatment, and follow-up, a manageable patient population with ADHD and similar disorders was selected and successfully treated in a private practice setting. PMID- 8200162 TI - The clinical characteristics and infectious outcomes of febrile infants aged 8 to 12 weeks. AB - We reviewed 356 consecutive cases of febrile infants aged 8 to 12 weeks who received outpatient evaluation for sepsis over 4 years. Thirty-three infants (9.3%) had a serious bacterial infection (SBI), including bacterial meningitis, bacteremia, urinary tract infection (UTI), and Salmonella enteritis. The SBI rate, which was directly proportional to fever height, was significantly greater for infants with hyperpyrexia (35%) than those with lesser degrees of fever (7.7%) and for infants with peripheral blood leukocytosis (total WBC count > or = 15,000/mm3; 25%) than those with lesser total WBC counts (5.8%). An attending level physician judged that 67% of infants with SBI appeared to be "well," including five or eight cases (63%) of bacteremia, 14 of 17 cases (82%) of UTI, and all three cases of Salmonella enteritis, whereas all five patients with bacterial meningitis appeared to be "ill." Urinalysis abnormalities indicative of UTI were present in 15 of 17 infants (88%) who had this infection. SBIs are not uncommon in febrile infants aged 8 to 12 weeks and occur significantly more often in those with either hyperpyrexia or peripheral blood leukocytosis. PMID- 8200163 TI - Infant positioning and SIDS. Acceptance of the nonprone position among clinic mothers. AB - In April 1992, the American Academy of Pediatrics recommended that healthy infants not be placed prone to sleep because of the association between the prone sleeping position and sudden infant death syndrome (SIDS). We determined the awareness and acceptance of this recommendation among 190 mothers attending a community health center pediatric clinic in the first year after the recommendation. Ninety-seven women (51.1%) had heard the recommendation. The compliance with the recommendation among women who had heard it was 63.9% (62 of 97). Fifty-three percent of all the mothers worried that their infant would choke in the supine position. More education is necessary in this population to improve acceptance of this new recommendation and to correct misinformation about the supine position. PMID- 8200164 TI - The effect of nutritional additives on anti-infective factors in human milk. AB - It has become a common practice to supplement human milk with a variety of additives to improve the nutritive content of the feeding for the premature infant. Twenty-two freshly frozen human milk samples were measured for lysozyme activity, total IgA, and specific IgA to Escherichia coli serotypes 01, 04, and 06. One mL aliquots were mixed with the following: 1 mL of Similac, Similac Special Care, Enfamil, Enfamil Premature Formula, and sterile water; 33 mL of Poly-Vi-Sol, 33 mg of Moducal, and 38 mg of breast-milk fortifier, and then reanalyzed. Significant decreases (41% to 74%) in lysozyme activity were seen with the addition of all formulas; breast-milk fortifier reduced activity by 19%, while no differences were seen with Moducal, sterile water, or Poly-Vi-Sol. No differences were seen in total IgA content, but some decreases were seen in specific IgA to E. coli serotypes 04 and 06. E. coli growth was determined after 3 1/2 hours of incubation at 37 degrees C after mixing. All cow-milk formulas enhanced E. coli growth; soy formulas and other additives preserved inhibition of bacterial growth. Nutritional additives can impair anti-infective properties of human milk, and such interplay should be considered in the decision on the feeding regimen of premature infants. PMID- 8200165 TI - Pulse oximetry at moderate altitude. Healthy children and children with upper respiratory infection. AB - Pulse oximetry is commonly used in both outpatient and inpatient settings to assess children with respiratory illness. This study was designed to obtain reference values for oxygen saturations in young children living at moderate altitude and to assess the impact of upper respiratory infection (URI) on oxygen saturation. We hypothesized that oxygen saturations of sick children at the University of Utah, Salt Lake City (1,500 meters above sea level), would be lower than oxygen saturations of those who were well. Eighty well children and 74 children with URI and nasal congestion were recruited from the University of Utah Pediatric Clinic. Subjects were 2 to 23 months of age. Oxygen saturations were recorded at 1-minute intervals for 5 minutes, and an average value was then calculated for each child. Mean oxygen saturation for well children (range 96% to 100%, mean 98.9%) corresponded to reported values at sea level. Oxygen saturations of children with URI were significantly lower (mean 97.5%, P < .001). Although the difference between well and sick children was statistically significant, given the small difference, URI cannot be considered the cause of clinically significant oxygen desaturation in previously healthy children at moderate altitude. PMID- 8200166 TI - Screening for maternal experiences of physical abuse during childhood. AB - Because a parental history of abuse during childhood is a documented risk factor for child abuse, pediatricians have been urged to assess parents' childhood discipline experiences. A brief set of questions was developed to detect a maternal history of childhood physical abuse that could be incorporated into a comprehensive psychosocial screening questionnaire. A criterion-based definition was used as the measure for physical abuse. In phase I, four screening questions were developed in a cross-sectional survey of 284 middle-class women attending a family medicine clinic, of whom 32% met the criteria definition for physical abuse. In phase II, the screening questions were tested in 428 mothers seen in Salt Lake City- and Seattle-area pediatric clinics. The four screening questions had a sensitivity of > 90%, a specificity of > 85%, a positive predictive value of > 75%, and a negative predictive value of > or = 90%--as compared with the criteria-based definition in both pediatric settings. These four screening questions compared favorably to a criteria-based definition of physical abuse during childhood and may be useful additions to psychosocial questionnaires. PMID- 8200167 TI - Thrombocytosis. Etiologic analysis of 663 patients. AB - Six hundred sixty-three children aged 1 to 16 years with thrombocytosis (defined as a platelet count of more than 500 x 10(9)/L) seen in a university hospital over a 1-year period were studied prospectively for etiology. The causes of thrombocytosis were infection (30.6%), hemolytic anemia (19.3%), tissue damage (15.2%), rebound thrombocytosis (14.8%), chronic inflammation (4.1%), renal disorders (4.1%), and malignancy (2%). Thrombocytosis associated with multiple, simultaneous causative factors was seen in 3.3% of cases. Among all patients with infections, osteomyelitis and septic arthritis were associated with higher platelet counts than other infections (P < .0001). Thrombocytosis secondary to infections was significantly more common in children under 5 years of age, whereas chronic inflammation, malignancy, and renal disorders were more common causes of thrombocytosis in children over 5 years of age. Thrombocytosis of 1 million or more platelets was seen in 13 (2%) children. No thrombocytosis-related complications were seen in any children, and none required any specific treatment. Thrombocytosis is a frequent finding in children. It is due to a variety of etiologic factors and is of little clinical discriminatory value. It is often due to an acute-phase phenomenon in response to infection, tissue damage, blood loss, or anemia, and is rarely due to malignancy. PMID- 8200168 TI - Tuberculous arthritis in children. Diagnosis by needle biopsy of the synovium. AB - In two children ages 8 months and 4 years, tuberculous synovitis of the knee was suggested by pathologic examination of synovial tissue obtained through needle biopsy. Culture of the biopsy material was positive for Mycobacterium tuberculosis in one case. In this child, the tuberculin test was negative, in the absence of anergy, at the time the child was first evaluated, and the primary lung lesion was not identified by the radiologist. Tuberculous synovitis has not previously been recognized as part of primary tuberculosis during the early weeks when the tuberculin skin test may be negative. Magnetic resonance imaging (MRI) is a sensitive modality for demonstrating joint fluid, synovial hypertrophy, and associated osteomyelitis, if present. With the increasing frequency of cases of tuberculosis in the population, greater awareness of the risk of tuberculous arthritis in childhood is important in order to recognize this unusual presentation. If negative early on, the tuberculin skin test should be repeated after 6 weeks of arthritis. A needle biopsy of the synovium is helpful and appropriate in all children with monoarticular arthritis who have a positive tuberculin skin test. PMID- 8200169 TI - Intravenous immunoglobulin in the treatment of Salmonella typhimurium infections in preterm neonates. AB - The purpose of this study was to determine the role of intravenous immunoglobulin (IVIG) administration in preterm neonates with S. typhimurium infection. A randomized trial of 47 preterm neonates with intestinal or extraintestinal S. typhimurium infection was performed. Neonates were randomly divided into two groups: 22 neonates were only given cefoperazone (group 1); 25 neonates were given cefoperazone plus IVIG (group 2). IVIG was given at a dose of 500 mg/kg on days 1, 2, 3, and 8 after entry into the study. Following treatment, bacteremia, complications, mortality rate, recovery time, and duration of antimicrobial therapy were evaluated in two groups. Bacteremia was found in 31.4% in group 1 and 8% in group 2 (P < .05); complications developed in 81.8% in group 1 and 16% in group 2 (P < 0.01); mortality was 40.9% in group 1 and 12% in group 2 (P < .05). Recovery took 15 days in group 1 and 8 days in group 2 (P < .01). The duration of antimicrobial therapy was 20 days in group 1 and 14 days in group 2 (P < .01). We conclude that IVIG treatment in combination with antibiotics in preterm neonates with S. typhimurium infection reduces the complications, mortality rate, and duration of therapy. PMID- 8200170 TI - Nasogastric or gastrostomy feedings in children with neurologic disabilities. AB - Although pediatricians are increasingly aware of the problem of undernutrition in children with neurologic disabilities, many of these children remain poorly nourished despite prolonged attempts at oral feedings. We studied the effects of tube feeding on such children, using either nasogastric (NG) or gastrostomy (GT) feedings. Twenty-six patients (16 male, mean age at first visit 40.7 months) were followed while receiving tube feedings for a mean of 23 months. Thirteen children in the NG group were tube fed by nasogastric tube. The GT group consisted of two groups of children: 10 who began with nasogastric feedings and then changed to gastrostomy because of intolerance or need for reflux surgery, and three who were always tube fed via gastrostomy. Mean percent ideal body weight for height age (%IBWH) for the whole group improved from 73.2% to 94.2% (P < .0001), for the NG group from 72.1% to 89.3% (P < .002), and for the GT group from 74.2% to 98.8% (P < .0001). One patient died of unrelated severe upper airway obstruction. No patients reported hospitalization due to tube-feeding complications. Seventeen of the parents perceived that their child's mood was improved and that they spent less time in child care after NG or GT feedings were begun. We conclude that (1) both nasogastric and gastrostomy feedings safely improved nutrition in these children and (2) this objective improvement was often accompanied by subjective improvement. We suggest aggressive use of tube feedings in selected patients. PMID- 8200171 TI - Xanthogranulomatous pyelonephritis in children. Etiology, pathogenesis, clinical and radiologic features, and management. PMID- 8200172 TI - Bilateral congenital anorchia in three siblings. PMID- 8200173 TI - Life-threatening methemoglobinemia in infants with diarrhea and acidosis. PMID- 8200174 TI - Bacterial tracheitis. An unusual radiographic presentation. PMID- 8200175 TI - Daytime urinary frequency. PMID- 8200176 TI - Are infant walkers hazardous to children's health? PMID- 8200177 TI - Severe electrical burns in a hemophiliac wearing a medical alert neck chain. PMID- 8200178 TI - Verotoxin-producing Escherichia coli in "idiopathic" thrombocytopenic purpura. PMID- 8200179 TI - Revised pediatric code card provides latest drug-dose and resuscitation guidelines. PMID- 8200180 TI - Stimulation of myocyte insulin-responsive glucose transporters by the inhibition of fatty acid oxidation. AB - The effects of the fatty acid inhibitor 4-bromocrotonic acid (4-BCA) on glucose utilization was studied in isolated rat myocytes. In contrast to its potent inhibition of [1-14C]palmitate oxidation, 4-BCA strongly stimulated the oxidation of [1-14C]glucose and [2-14C]-pyruvate in a concentration-dependent manner. At a concentration of 300 microM, 4-BCA increased glucose oxidation threefold and that of pyruvate oxidation twofold. The rate of transport of [U-14C]-2-deoxyglucose was significantly stimulated by 4-BCA. The transport of 2-deoxyglucose was increased sevenfold with 200 microM 4-BCA, whereas insulin (10 microU)/ml enhanced 2-deoxyglucose transport twofold. The addition of insulin to myocytes preincubated with 4-BCA did not further increase glucose transport. Cytochalasin B and anti-GLUT 4 antibody decreased the 4-BCA-induced stimulation of glucose transport. These results suggest that the stimulation of 2-deoxy-glucose transport by 4-BCA occurs through an increase in the activity of insulin responsive glucose transporters, GLUT 4, in the sarcolemmal membrane. PMID- 8200181 TI - Dichotomous response of whole blood viscosity in streptozotocin-diabetic rats. AB - Abnormalities of blood rheology may play an important role in the underlying mechanism of the development of diabetic complications. Although streptozotocin (STZ)-induced diabetic rats have been used extensively in the investigation of diabetic complications, blood rheological alterations in this model have not previously been assessed. To assess one aspect of blood rheology, we repeated whole blood viscosity (WBV) measurements at 4, 8, 12 and 16 weeks after the STZ injection in rats. Nine of fifteen diabetic rats showed increased WBV after the induction of diabetes. Although these rats had a higher haematocrit, the increase in WBV was maintained after correction to a standard haematocrit. Percentage changes of WBV were significantly greater in these diabetic rats than in control rats at low shear rates (0.1s-1 and 1.0s-1), but not at high shear rates. In contrast, WBV was lowered at all shear rates after the injection of STZ in the remaining six diabetic rats which had lower haematocrit, severe weight loss and high mortality; no rats survived for 16 weeks post-injection. Animals in this group may be implicated in the high mortality among STZ-diabetic rats. Although there was a clear distinction of rheological and clinical pictures between these two groups of STZ-diabetic rats, blood glucose and HbA1 concentrations did not differ significantly. This study demonstrates a dichotomy in blood viscosity response to STZ-induced diabetes. PMID- 8200182 TI - Effects of short-time insulin suppression on renal sodium excretion in type II diabetic hypertensives. AB - The effects of a short-time insulin suppression on Na+ excretion were evaluated in 9 type II diabetic hypertensive males. All patients had a body mass index < 26 and normal plasma lipid levels. After 2 weeks under constant NaCl intake (120 mEq of NaCl daily) either octreotide, a somatostatin analogue, or its vehicle were infused in a forearm vein during acute volume expansion (0.20 ml/kg/min isotonic saline given intravenously over a period of 30 min). A double blind randomized cross-over design was followed, and each patient was given both infusions at one week interval. Blood and urine samples for the evaluation of plasma insulin and serum and urine Na+ were taken at time-30, 0, 30, 60, 90, 120, and 240 min. Our data showed that octreotide completely suppressed insulin levels (from time 0 to 60 min). During acute volume expansion+octreotide, Na+ excretion was 0.20 +/- 0.15 mEq/min at time 0, 0.23 +/- 0.21 mEq/min at time 30, 0.64 +/- 0.24 mEq/min at 60 (p < 0.05 vs time 0), 0.71 +/- 0.35 mEq/min at 90 (p < 0.05 vs time 0), 0.78 +/- 0.10 mEq/min at 120 (p < 0.01 vs time 0) and 0.71 +/- 0.12 mEq/min at 240 min (p < 0.05 vs time 0). As compared to acute volume expansion alone, octreotide induced a significant increase of Na+ excretion at 60 and 90 min (p < 0.05). In conclusion, a short-time insulin suppression, as obtained by the somatostatin analogue octreotide, enhances the natriuretic response to intravenous saline load in lean type II diabetic hypertensives. PMID- 8200183 TI - Alterations in Na+/K(+)-ATPase activity and fluidity of erythrocyte membranes from relatives of insulin dependent diabetic patients. AB - Several plasma membrane alterations have been described in diabetes mellitus. Data reported in gestational diabetes mellitus (GDM) suggested that these alterations might be present before the onset of overt metabolic derangement. On the basis of these data it is tempting to hypothesize that the reduction in the sodium pump activity might be due to a genetic factor acting at the membrane level before the onset of diabetes. In order to verify this hypothesis 11 insulin dependent diabetic patients, 15 first degree relatives of the patients and 10 healthy subjects with a negative family history for diabetes mellitus were studied. Fluidity, Na+/K(+)-ATPase activity and membrane cholesterol content (C) were evaluated on plasma membranes obtained from red blood cells (RBCs). Na+/K(+) ATPase activity was reduced with a contemporary increase in membrane fluidity in RBCs from IDDM patients in comparison to either relatives and controls. The same alterations were observed also in RBCs from the relatives in comparison to controls. We did not find any significant difference in the C content among the three groups. Data herein reported provide evidence that a reduction in the Na+/K(+)-ATPase activity is present in the plasma membrane of relatives of diabetic subjects. Furthermore, the present work suggests that the change in enzymatic activity might be related to modifications in membrane fluidity. PMID- 8200184 TI - Effect of hyperlipacidemia on plasma C-peptide concentration during euglycemic hyperinsulinemic clamp. AB - During constant infusion of exogenous human insulin and glucose to healthy volunteers, a rise in glycemia was still able to stimulate the B-cell as judged from the increase in C-peptide plasma concentration. Nevertheless, under euglycemic conditions, the C-peptide concentration fell well below its initial level. This coincided, however, with severe hypolipacidemia. When the latter phenomenon was corrected through the simultaneous administration of exogenous triglycerides and heparin, a reascension in C-peptide plasma concentration was observed despite persistent hyperinsulinemia. It is proposed, therefore, that the hyperinsulinemic-euglycemic clamp procedure does not represent a reliable approach to explore the possible feedback action of insulin upon its own secretion rate, because of the interference upon B-cell secretory activity of factors such as changes in lipacidemia. PMID- 8200185 TI - The ethical conduct of health services research: a case study of 55 institutions' applications to the SUPPORT project. PMID- 8200186 TI - Pathophysiology of acute respiratory failure. AB - The term respiratory failure implies the inability to maintain either the normal delivery of oxygen to tissues or the normal removal of carbon dioxide from the tissues. There are actually three processes involved: the transfer of oxygen across the alveolus, the transport of tissues (by cardiac output), and the removal of carbon dioxide from the blood into the alveolus with subsequent exhalation into the environment. Failure of any step in this process can lead to respiratory failure. An overview of the normal physiology of pulmonary gas exchange and the pathophysiology of respiratory failure is presented in this article. PMID- 8200187 TI - Acute inhalation injury. AB - Toxic inhalants cause injury through a variety of different mechanisms, including direct irritation of the respiratory tract mucosa, asphyxiation, and systemic absorption of the toxin. The nature and extent of the acute injury depends on the inhalant's water solubility, aerodynamic features, pH, and concentration. In addition, a patient's underlying respiratory function may affect the clinical response. Smoke inhalation is a particularly challenging clinical problem because patients often are exposed to a large number of inhaled toxins and may suffer thermal injury to the respiratory tract as well. Several chronic respiratory problems have been identified following acute inhalation injuries. Chronic airflow obstruction has been reported in patients exposed to ammonia, chlorine, nitrogen dioxide, and sulfur dioxide; bronchiolitis obliterans may follow exposure to nitrogen dioxide and sulfur dioxide. Inhalation injuries can be difficult to manage because exposures occur infrequently, and the exact toxic agents involved often are not known immediately. Prevention of occupational exposures remains a cornerstone in the overall management of inhalation injuries. PMID- 8200188 TI - Aspiration emergencies. AB - Aspiration of foreign material into the lungs can represent a medical emergency requiring timely interventions to assure a favorable outcome. Establishment of a patent airway and maintenance of adequate oxygenation are the initial requirements for successful treatment of all types of aspiration emergencies. The nature of the aspirated material dictates further interventions and potential outcome. PMID- 8200189 TI - Airway management in respiratory emergencies. AB - Securing the airway is an important first step in respiratory emergencies. In this article, general principles of airway management are reviewed. The techniques of tracheal intubation, including surgical routes of airway access, are discussed in reference to special circumstances that can arise in acute airway management. PMID- 8200190 TI - Chest trauma. Assessment, diagnosis, and management. AB - In the United States, trauma is the leading cause of death in people under 40 years of age. Chest trauma is a relatively common but potentially lethal injury and requires a high level of suspicion, rapid diagnosis, and appropriate therapy. Methods for the assessment, diagnosis, and treatment of chest trauma are discussed in this article. PMID- 8200191 TI - Massive hemoptysis. Assessment and management. AB - The first priorities in treating the patient with massive hemoptysis are to maintain the airway, optimize oxygenation, and stabilize the hemodynamic status. The major question to be answered is whether or not the patient should be intubated for better gas exchange, suctioning, and protection from sudden cardiorespiratory arrest. If the bleeding site is known, the patient should be placed with the bleeding lung in the dependent position. Once stabilization is accomplished, diagnostic and therapeutic interventions should be promptly performed because recurrent bleeding occurs unpredictably. Early bronchoscopy, preferably during active bleeding, should be performed with three goals in mind: to lateralize the bleeding side, localize the specific site, and identify the cause of the bleeding. In those patients with lateralized or localized persistent bleeding, immediate control of the airway may be obtained during the procedure with topical therapy, endobronchial tamponade, or unilateral intubation of the nonbleeding lung. If bleeding continues but the side of origin is uncertain, lung isolation or use of a double-lumen tube is reasonable, provided that the staff is skilled in this procedure. If the bleeding cannot be localized because the rate of hemorrhage makes it impossible to visualize the airway, emergent rigid bronchoscopy or emergent arteriography is indicated. Arteriography and embolization should be used emergently for both diagnosis and therapy in those patients who continue to bleed despite endobronchial therapy. Emergent surgical intervention should be considered in operative candidates with unilateral bleeding when embolization is not available or not feasible, when bleeding continues despite embolization, or when bleeding is associated with persistent hemodynamic and respiratory compromise. For patients in whom bleeding has ceased or is decreased, emergent intervention may not be necessary. If the bleeding site has been localized or lateralized with early bronchoscopy, recurrent bleeding can be managed more confidently and rapidly. The cause of bleeding can be determined at bronchoscopy in patients with endobronchial adenomas, carcinomas, foreign bodies, or broncholiths. If no diagnosis is obtained at bronchoscopy, elective angiography of the bronchial and, if necessary, the pulmonary vasculature is reasonable. The precise timing and nature of the further evaluation are dictated by the suspected underlying pathologic process and the clinical condition of the patient. Surgery is the most definitive form of therapy for patients with hemoptysis because it removes the source of bleeding. Whether to proceed with elective surgery in patients with a major bleed that stops or one that is controlled angiographically is a difficult decision. Little data are available to assist in this decision, even for specific diseases, such as bronchiectasis. Similarly, the long-term course of patients treated with endobronchial tamponade or topical therapy is unknown. For patients with inoperable disease, limited reserve, or bilateral progressive disease, embolization frequently controls bleeding for prolonged periods.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8200192 TI - Diagnosis and management of upper airway obstruction. AB - Upper airway obstruction is a potentially fatal condition that requires prompt diagnosis and treatment. Common causes include foreign body aspiration, infections (even in the adult population) and sequelae of intubation, tracheostomy, and transtracheal oxygen catheters. Spirometry is an insensitive test for diagnosing upper airway obstruction and reflects the functional, rather than anatomic, severity of an obstruction. Although simple tomography still plays an important role, CT and magnetic resonance imaging scans are useful additions to our diagnostic armamentarium. Advances in laser technology, surgery, and bronchoscopy have broadened treatment options but require further evaluation. PMID- 8200193 TI - Respiratory distress in the ventilated patient. AB - The onset of agitation and distress in a mechanically ventilated patient should initiate a careful assessment that considers whether there has been progression of the underlying disease, a new medical complication, or adverse effects from medical interventions and procedures, including intubation and mechanical ventilation. This article focuses on problems that relate to mechanical ventilation and the interactions of the "patient-ventilator system". The authors suggest an initial approach to the patient who develops respiratory distress, and then review the appropriate indications for sedative and paralytic medications. PMID- 8200194 TI - Pneumothorax and barotrauma. AB - This article discusses pneumothorax and barotrauma from the viewpoints of both the intensivist/pulmonologist and the emergency room physician because both groups of clinicians frequently encounter these potentially life-threatening conditions. The discussion focuses primarily on pneumothorax and barotrauma as they occur in adults rather than in neonates and children. PMID- 8200195 TI - Respiratory failure as a result of drugs, overdoses, and poisonings. AB - When taking care of critically ill patients, it is paramount to consider all factors that could be contributing to their illness. Even in this brief discussion, it is clear that numerous drugs, procedures, and ingestants are associated with acute respiratory failure from a variety of mechanisms and that a review of all possible drug/poison exposures needs to be done for every patient. PMID- 8200196 TI - What is feasible in a diabetic clinic? The diabetologist's charter. PMID- 8200197 TI - The use of gamma linolenic acid in the prevention and treatment of diabetic neuropathy. AB - A substantial disturbance of the metabolism of the n-6 essential fatty acids (EFAs) exists in both human and experimental diabetes mellitus. The process of conversion of dietary linoleic acid to gammalinolenic, dihomogammalinolenic and arachidonic acids, and other polyunsaturates is inadequate in diabetic patients. Disturbances of these EFAs and the 1- and 2-series prostaglandins derived from them cause a variety of microvascular, haemorheological, and other abnormalities leading to reduced blood flow and neural hypoxia. This will in turn produce an escalating cycle of further hypoxia through the generation of oxygen-free radicals and aggravation of neural capillary endothelial damage. Endoneurial hypoxia impairs axonal transport, produces demyelination, and reduces neural ATP ase activity. Furthermore, depletion of polyunsaturated fatty acids derived from n-6 pathway may lead to abnormalities of myelin turnover, membrane-bound proteins (such as enzymes and receptors) and other axonal structural abnormalities. The disorders postulated here may synergistically interact with the metabolic changes described in both the glycosylation and the myoinositol hypotheses and may have important implications in the approach to treat diabetic neuropathy. PMID- 8200198 TI - Blood pressure, diet and the progression of nephropathy in patients with type 1 diabetes and hypertension. AB - To examine the relationships between the normal dietary intakes of protein and phosphate, blood pressure, and the progression of diabetic nephropathy, we prospectively studied 20 Type 1 diabetic subjects of mean age 43 +/- 10 years (SD) with early nephropathy (mean serum creatinine 115 +/- 43 mumol l-1) over 1 year. Three-monthly measurements of blood pressure, glycaemic control, and normal dietary intake (3-day weighed food records) and 6-monthly measurements of glomerular filtration rate (using a single injection of chromium 51-EDTA) were made. GFR changed at a median rate of -0.89 ml min-1 1.73 m-2 month-1 (range +0.85 to -2.55 ml min-1 1.73 m-2 month-1). Mean dietary protein intake (1.22 g kg 1; range 0.78 to 1.55 g kg-1) and phosphate intake (21.5 mg kg-1; range 14.1 to 30.4 mg kg-1) were not significantly related to the rate of change in GFR. Only mean systolic blood pressure was significantly related to change in GFR, and accounted for 45% of the variability in GFR decline in the 18 subjects who completed the study (r = 0.67; R2 = 0.449; F1,16 = 13.2; p < 0.005; 95% confidence interval for r: 0.336-0.867). A mean systolic blood pressure of 140 mmHg or below was associated with no significant decline in GFR over a median period of 13 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200199 TI - Relationship between blood pressure and urinary albumin excretion rate in young Danish type 1 diabetic patients: comparison to non-diabetic children. Danish Study Group of Diabetes in Childhood. AB - In 1989 a nation-wide investigation of blood pressure and urinary albumin excretion rate (AER) was carried out in 506 boys and 441 girls with Type 1 diabetes (approximately 80% of total) treated at 22 paediatric departments. In addition a reference population from 1979 consisting of 663 healthy non-diabetic children (334 boys, 329 girls) served as a control group with respect to blood pressure and body mass index. Microalbuminuria was defined as AER of 20-150 micrograms min-1 in at least two out of three timed overnight urine collections and was diagnosed in 30 adolescents (16 boys, 14 girls). Five patients (3 boys, 2 girls) had overt proteinuria (AER: > 150 micrograms min-1). Age-related percentile charts based on one blood pressure reading were provided for normoalbuminuric diabetic patients and the healthy control group. The study revealed an increase in arterial blood pressure during the period of the pubertal growth spurt for the diabetic and non-diabetic group. The changes were most pronounced for systolic blood pressure. No statistically significant difference was observed in systolic and diastolic blood pressure between normoalbuminuric diabetic children and healthy control children. However, diabetic females aged 15 18 years had significantly higher diastolic blood pressure (75 +/- 1 mmHg, n = 139, mean +/- SE) than healthy control females (72 +/- 1 mmHg, n = 155, p < 0.01), and significantly (p < 0.001) higher body mass index (diabetic females: 22.3 +/- 0.2 kg m-2 vs healthy females: 20.9 +/- 0.2 kg m-2, mean +/- SE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200200 TI - Acute myocardial infarction in diabetic patients in the thrombolytic era. AB - To examine the benefits of thrombolytic therapy in diabetic patients with acute myocardial infarction a retrospective study of all diabetic and non-diabetic patients with acute myocardial infarction admitted to the coronary care unit of the General Hospital, Birmingham between January 1984 and December 1987 was made and findings compared to corresponding groups admitted between January 1990 and May 1992 when thrombolytic therapy was routine. In-hospital mortality and morbidity were assessed in 208 diabetic and 1029 non-diabetic patients with acute myocardial infarction admitted 1984 and 1987 and in 115 diabetic and 501 non diabetic patients with myocardial infarction between January 1990 and May 1992. Following the introduction of thrombolytic therapy, there was a reduction in mortality among non-diabetic patients from 17% to 8.5%; p < 0.001 (observed reduction: 49%; 95% CI: 30-70%) and in the incidence of left ventricular failure (from 22% to 8%, p < 0.1 (observed reduction: 52%; 95% CI: 40-85.5%). Diabetic patients showed a reduction in mortality from 30% to 17%; p = 0.02 (observed reduction: 42%; 95% CI: 9.4-73.8%) and in the incidence of left ventricular failure from 39% to 21%; p < 0.01 (observed reduction: 45%; 95% CI: 20.3-72.5%). Thrombolytic therapy confers a major benefit on diabetic patients with acute myocardial infarction, although this group remains at a prognostic disadvantage compared to non-diabetic patients. PMID- 8200201 TI - Interpreting hospital admissions data across the Korner divide: the example of diabetes in the north western region. AB - Hospital admission rates and hospital bed utilization rates are presented for all admissions assigned to diabetes mellitus as principal cause in the North Western Region from 1980/81 to 1990/91. Data are derived from Hospital Activity Analysis (1980/81-1986/87) and from the Regional Information System (1988/89-1990/91). Admission rates for all categories of diabetes combined showed little change until 1986/87 after which they rose progressively each year. Hospital bed utilization rates fell progressively from 1986/87 onwards, the number of bed days attributed to diabetes falling from 1.9% to 0.8% of the total for all causes. Most of the rise in admission rates from 1988/89 onwards was attributable to diabetes with ophthalmic complications (ICD 250.4). This was heavily influenced by the enumeration of day cases in the Regional Information System. When these are discounted, admission rates for the more recent years are stable. Diabetes without mention of complications (ICD 250.0) showed the most dramatic decline in its contribution to hospital bed utilization. This may be the result of increasing outpatient support from diabetes specialist nurses whose numbers increased in inverse proportion to the fall in bed utilization attributed to ICD 250.0. PMID- 8200202 TI - The effect of diabetes and impaired glucose tolerance on mortality in Malta. AB - A random sample of the middle-aged population of Malta was studied in a diabetic survey in 1981. Among the 1537 survey responders, in 659 men and 878 women aged 40 years or more the prevalence of diabetes was 16% in men and 18% in women, and that of IGT 5% in both sexes. By the end of 1985, 90 subjects (49 men: 41 women) had died. Mortality/100 (95% CI) was among subjects with normal, impaired glucose tolerance and diabetes in the age group 40-59 years 12 (5-19), 25 (23-73), and 61 (17-148), and in the age group of more than 60 years, 102 (68-136), 148 (59-237), and 178 (122-234), respectively. Age standardized mortality/1000 was in men 51, 28, and 100, and in women 34, 33, and 72 in the three categories of glucose tolerance, respectively. Among diabetic subjects aged 40-64 years the risk of death was increased seven-fold as compared with normoglycaemic subjects. Among men there was an inverse association between body mass index and mortality in all categories of glucose tolerance. Among women, no clear trend between body mass index and mortality was found. The relative risk of death for subjects with diabetes adjusting for age, sex, and body mass index was 2.2 (odds ratio: 95% CI 1.40 to 3.42) as compared with non-diabetic subjects. The age-adjusted survival curves for normoglycaemic subjects were similar for men and women. Among subjects with abnormal glucose tolerance the survival was slightly better in women than in men (p = 0.056). About half of the deaths were from cardiovascular disease and 7% from diabetes mellitus. PMID- 8200203 TI - Fetal proinsulin and birth weight. AB - In both diabetic and non-diabetic pregnancies fetal insulin is an important anabolic hormone. Fetal hyperinsulinaemia is associated with accelerated fetal growth and increased birth weight. Insulin and C-peptide concentrations in both umbilical cord and amniotic fluid reflect fetal beta-cell secretion and are correlated with birth weight. In the present study umbilical venous proinsulin and insulin concentrations were measured in 54 term infants born to women with and without mild disturbances of glucose tolerance. Umbilical venous cord proinsulin, assayed using a highly specific immunoradiometric assay, was independently correlated with infant birth weight (Rho = 0.53, p < 0.0001) and birth percentile (Rho = 0.65, p < 0.0001). The correlation between birth weight and birth percentile weight with umbilical venous insulin, measured using a non specific insulin assay, was lost following correction for the influence of proinsulin. Umbilical venous cord proinsulin appears to be a good indicator of fetal beta-cell activity, and in this study, a superior marker to insulin assayed using a non-specific insulin radioimmunoassay. The longer half-life of proinsulin compared with insulin may contribute to proinsulin being a more robust marker of overall fetal beta-cell activity than insulin. PMID- 8200204 TI - Growth during childhood and final height in type 1 diabetes. AB - The growth of 184 children with Type 1 diabetes was analysed using data collected prospectively in the Oxford district between 1969 and 1992. The overall mean height standard deviation score (Ht SDS +/- SD) at diagnosis was 0.35 +/- 1.05 which was significantly greater than the national standard of Tanner (1966). However, there is evidence of a secular trend in the heights of Oxford children over the last 20 years when compared with Tanner. When data from children with diabetes were compared with local controls, it was only the children aged 5-10 years at diagnosis who were taller (Ht SDS +/- SD, 0.58 +/- 1.14, versus 0.31 +/- 0.90, n = 73, p < 0.05). Those diagnosed under the age of 5 years (n = 37) were shorter (Ht SDS 0.12 +/- 0.93) and those diagnosed aged more than 10 years (n = 74) were similar in size (Ht SDS 0.22 +/- 0.98) to controls. These differences could not be explained by social class. Loss of height occurred between diagnosis and puberty, particularly in those diagnosed between the ages of 5 and 10 years. The pubertal growth spurt was blunted in all groups but this abnormality was more profound in the girls (mean peak height velocity SDS -1.09 +/- 1.02, p < 0.0005) than in the boys (mean peak height volocity SDS -0.5 +/- 1.14, p < 0.025). The mean final height SDS was -0.74 +/- 0.96 in those diagnosed < 5 years, 0.00 +/- 1.26 in those diagnosed between the ages of 5 and 10 years and 0.09 +/- 1.10 in those aged more than 10 years at diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200205 TI - Prevalence of islet cell and thyrogastric autoantibodies in Sudanese patients with type 1 diabetes. AB - In this study, sera from 96 Sudanese patients with Type 1 diabetes and from 86 matched controls were tested for the following organ-specific antibodies: islet cell antibodies (ICA), thyroid microsomal antibodies (TMA), antithyroglobulin antibodies (ATA), and gastric parietal cell antibodies (PCA). In diabetic patients the prevalence rates of these antibodies were: ICA = 41.7%, ATA = 2.0%, TMA = 7.3%, PCA = 6.3%. All these rates were significantly higher than in controls except for ATA which showed similar low prevalence rates in patients and controls. The pattern of prevalence of these antibodies by age, sex, and duration of diabetes was assessed and compared with reports from other populations. The general pattern of these antibodies is similar to that reported in Caucasian populations, except for a slightly greater tendency for ICA to persist with increased duration of diabetes in our sample. Furthermore, the low prevalence of TMA in our population is comparable to that reported in Black American diabetic patients but significantly lower than rates reported in certain other racial groups. PMID- 8200206 TI - Mutations in the glucokinase gene are not a major cause of late-onset type 2 (non insulin-dependent) diabetes mellitus in Japanese subjects. AB - The role of the glucokinase gene in the development of diabetes in a group of 349 Japanese subjects with late-onset Type 2 diabetes was examined. These diabetic subjects and 197 non-diabetic controls were typed at two simple tandem repeat DNA polymorphisms in the glucokinase gene termed GCK2 and GCK3. Six and five alleles were evident in Japanese subjects at GCK2 and GCK3, respectively. There were no significant differences in allele, genotype or haplotype frequencies between diabetic and normal groups. In addition, the glucokinase gene of 340 diabetic and 170 non-diabetic Japanese subjects was screened for mutations using single strand conformation polymorphism analysis. Four nucleotide substitutions were identified: a silent substitution in exon 4 in the codon for proline 145 (CCC- >CCG), and A-->T, C-->G, and C-->A substitutions in introns 1b, 3, and 5, respectively. There were no significant differences in the frequencies of these nucleotide substitutions between diabetic and non-diabetic groups. These results suggest that glucokinase gene defects are not a major cause of late-onset Type 2 diabetes in Japanese subjects. PMID- 8200207 TI - Glucokinase gene polymorphisms: a genetic marker for glucose intolerance in a cohort of elderly Finnish men. AB - Although mutations in the glucokinase gene are implicated in the pathogenesis of glucose intolerance in pedigrees with maturity-onset diabetes of the young, the role of such mutations in typical Type 2 diabetes is poorly characterized. We studied a cohort of elderly men born (between 1900 and 1919) in two Finnish communities and exhibiting a continuous spectrum of glucose tolerance at assessments made in 1984 and 1989. Individuals were typed at two polymorphic microsatellites straddling the glucokinase gene, GCK(3') (n = 169) and GCK(5') (n = 166): these two markers were in linkage equilibrium in this cohort. Significant associations between alleles at the GCK(3') marker and glucose tolerance were evident (p = 0.002), the frequency of the (z + 2) allele rising from zero in control subjects (n = 88 chromosomes) to 6.5% (n = 62) in subjects with impaired tolerance and 12.2% (n = 188) in subjects with diabetes. Mean 2-h glucose levels were 10.5 (9.6-11.4, 95% confidence interval) mmol l-1 in individuals with the (z + 2) allele and 8.1 (7.6-8.7) mmol l-1 in those without (p = 0.01, corrected for multiple comparisons). No association was evident between GCK(5') alleles and glucose tolerance. The GCK(3') microsatellite is a marker for abnormal glucose tolerance in this cohort of elderly Finnish men. PMID- 8200208 TI - Cerebral glucose metabolism in type 1 diabetic patients. AB - To evaluate whether cerebral glucose metabolism is impaired in diabetes the [18F] 2-deoxy-2-fluoro-D-glucose method and positron emission tomography were used to determine the regional cerebral metabolic rate of glucose in 12 healthy subjects, 8 newly diagnosed Type 1 diabetic patients 6 Type 1 diabetic subjects without peripheral neuropathy, and 7 Type 1 diabetic patients with symptomatic peripheral neuropathy, all of whom were men. In addition, multimodal evoked potentials were assessed. Cerebral glucose consumption was significantly reduced in the group with neuropathy as compared with the newly diagnosed diabetic patients and the healthy subjects (26.9 +/- 1.0 vs 33.9 +/- 1.9 and 32.5 +/- 1.1 mumol 100 g-1 min 1; p < 0.05), while in the patients without neuropathy it was 30.2 +/- 2.5 mumol 100 g-1 min-1 (NS vs the remaining groups). There were no significant differences between the groups regarding brainstem auditory and visual evoked potentials. No relationship was noted between cerebral glucose metabolism and P300 latency of event-related potentials as an index of cognitive function, but there was an inverse correlation with age (r = -0.42; p < 0.05) and duration of diabetes (r = 0.67; p < 0.05). These results suggest that cerebral glucose metabolism is normal at the time of diagnosis of Type 1 diabetes, but may become altered with both increasing duration of diabetes and age in the absence of central conduction deficits or cognitive dysfunction. Diabetic neuropathy may constitute a possible additional correlate of reduced cerebral glucose consumption. PMID- 8200209 TI - Diabetes and alternative medicine: cause for concern. AB - 'Alternative' medicines are becoming increasingly popular, and in this paper we describe our experience with alternative approaches to orthodox diabetes management. Four patients with insulin-dependent diabetes reduced or stopped their insulin in favour of therapeutic approaches including prayer, faith healing, unusual diets, and supplements of vitamins and trace elements. This resulted in ketoacidosis in three, in one case life-threatening; and weight loss and hyperglycaemia in the other. One patient developed serious retinopathy. Additionally, eight other types of alternative diabetic treatment are described, not as far as we know associated with such serious complications. These include homeopathy, reflexology, meditation, herbal treatment, 'cellular nutrition', 'subconscious healing', 'pearl therapy' (drinking milk in which pearls have been boiled) and 'astrotherapy' (typing pieces of coral around the arm). Diabetes is a chronic incurable disease, for which modern treatments remain somewhat unsatisfactory. It is therefore perhaps not surprising that some patients seek alternative treatments with more attractive claims. Diabetes health professionals need to be aware of the potential dangers associated with some of these treatments. PMID- 8200210 TI - A ward comparison between the One Touch II and Glucometer II blood glucose meters. AB - A 6-week clinical evaluation of the One Touch II blood glucose meter was performed in a medical ward specializing in diabetic patients and compared to the existing Glucometer II system. Nursing staff trained in both methods performed 267 capillary blood glucose measurements using the two meters. A reference capillary blood glucose was performed simultaneously on 129 of these occasions using a Yellow Springs Instrument analyser. The One Touch II correlated better with the reference (r = 0.97) than the Glucometer II (r = 0.86) and was equally close or closer to the Yellow Springs Instrument on 82% of occasions. A greater proportion of samples measured by the One Touch II were within 15% of the reference value (83% vs 66%). There were also 17 cases where the One Touch II was able to give a measurement which was outwith the analytical range of the Glucometer II. A questionnaire revealed the nursing staff unanimously preferred using the One Touch II to their present meter. It is concluded that in a ward setting the One Touch II meter showed improved accuracy, usefulness in its wider analytical range, and a greater user preference in comparison to the Glucometer II. PMID- 8200211 TI - The Eleventh Anglo-Danish-Dutch Diabetes Group Meeting. PMID- 8200212 TI - Implementing the lessons of DCCT. Report of a national workshop under the auspices of the British Diabetic Association. PMID- 8200213 TI - Toxicology of depot medroxyprogesterone acetate. AB - Depo-Provera (depot-medroxyprogesterone acetate or DMPA), administered either subcutaneously or intramuscularly, has undergone a thorough toxicological evaluation in a number of animal species. DMPA has been tested in short- and long term toxicity studies in rodents, rabbits, and monkeys. It has been examined for its effects on reproduction in mice, rats, and rabbits, and for carcinogenic potential in rats, mice, beagle dogs, and rhesus monkeys. Genotoxicity tests have been performed in vitro and in vivo. This paper describes the toxicology data submitted to the US FDA in support of the New Drug Application (NDA) for Depo Provera as well as data published in the literature. When interpreted in the light of the available pharmacokinetic information, these data demonstrate that DMPA is not significantly different from other contraceptive progestogens in its toxic and tumorigenic potential. PMID- 8200215 TI - Breast cancer and depot-medroxyprogesterone acetate: a review. AB - Depot-medroxyprogesterone acetate (DMPA) has been used world-wide since 1964 as a contraceptive in spite of the fact that it was only in 1992 licensed for contraceptive use in the USA due to concern about a possible breast cancer risk. Two recent studies have considered DMPA use and risk of breast cancer and these and earlier studies are reviewed here. Overall, the results are reassuring but there is some evidence that breast cancer risk may be increased in women using DMPA when very young and particularly in recent users. Current knowledge of the biology of human breast cancer is such that it is difficult to judge the biological plausibility of this evidence. There is no doubt that DMPA is a highly effective form of contraception and any overall assessment must take into account all the relevant risks and benefits. Thus, the risk-benefit equations in developed and developing countries must allow for different levels of maternal mortality and morbidity, as well as differing underlying cancer rates. PMID- 8200214 TI - Depot-medroxyprogesterone acetate (DMPA) and cancer of the endometrium and ovary. AB - This review addresses possible associations between depot-medroxy-progesterone acetate (DMPA) and endometrial and epithelial ovarian cancers. Two unexpected endometrial carcinomas were observed at autopsy of rhesus monkeys treated for 10 years with 50 times the human doses of DMPA. A record linkage in the USA did not suggest any association between DMPA and endometrial cancer. A multicentre case control study in Thailand showed a strong protective effect of DMPA for endometrial cancer. Studies from the USA, Mexico and Thailand did not observe any association between use of DMPA and epithelial ovarian cancer. The available information, therefore, indicates that use of DMPA protects against endometrial cancer and is not associated with epithelial ovarian cancer. PMID- 8200216 TI - Depot-medroxyprogesterone acetate, other injectable contraceptives, and cervical neoplasia. AB - The relationship between depot-medroxyprogesterone acetate (DMPA), and other injectable contraceptives and cervical neoplasia was reviewed mainly on the basis of three studies: the WHO Collaborative Study of Neoplasia and Steroid Hormone Contraceptives (2,009 cases and 9,583 controls collected in several, mainly developing, countries); a study of 369 cases of carcinoma in situ, 133 of invasive cancer and 646 controls collected by the National Tumor Registry of Costa Rica; and a cooperative study of 759 cases of invasive cervical cancer and 1,430 controls from four countries in Latin America (Costa Rica, Peru, Mexico and Colombia). There was no evidence of an appreciably elevated risk since most relative risks for ever users ranged from between 0.8 and 1.4, nor of consistent duration-risk relationship which was observed only in one study. The relative risk estimates for longest duration of use ranged from between 0.9 and 2.4. The data are still compatible with the absence of a causal association and with a moderately increased risk (up to a factor 1.5), which finds some biological plausibility as it is in agreement with the overall evidence of the relation between oral contraceptives and cervical neoplasia. PMID- 8200217 TI - Contraceptive efficacy of the Copper T 380A and Copper T 200 intrauterine devices: results from a comparative clinical trial in six developing countries. AB - The clinical performance of the Copper T 380A (TCu 380A) and the Copper T 200 (TCu 200) intrauterine devices (IUDs) was evaluated for 12 months in a group of women who had one of the two IUDs inserted. Results are from a multicenter randomized clinical trial at one site in each of six developing countries. The pregnancy rate with the TCu 380A IUD was significantly lower than the pregnancy rate with the TCu 200 IUD at 12 months (0.5 and 2.6 per 100 women, respectively, p < 0.01). No statistically significant differences between the two study IUDs were found with regards to expulsion or removals due to bleeding/pain, personal, medical, or planned pregnancy. The TCu 380A IUD did not have a disproportionately higher incidence of side effects such as intermenstrual bleeding or pain, inflammations or infections, or insertion-related events compared to the TCu 200 IUD. TCu 380A IUD users, however, were significantly more likely to report increased dysmenorrhea than were TCu 200 IUD users. The performance of the TCu 380A IUD in preventing pregnancy during this trial indicates that this IUD may be a better option than the TCu 200 IUD for women wishing to practice effective, long-term, reversible birth control without having to resort to hormonal methods. PMID- 8200218 TI - Tissue and serum levels of steroid hormones and RU 486 after administration of mifepristone. AB - The present study was designed to examine the effect RU 486 administration on steroid hormone levels in serum and decidua. Sixty women at 6-7 weeks gestation were divided into three groups. The first group took a placebo 24 hours before interruption of pregnancy. The other two groups took 200 mg mifepristone 12 and 24 hours before the surgical procedure, respectively. The concentrations of steroids and mifepristone were measured by radioimmunoassay or high performance liquid chromatography. Mifepristone treatment increased the levels of estradiol, cortisol and testosterone in serum and decidual cytosol (p < 0.05 or p < 0.01). A minor elevation in progesterone level was observed but was not statistically significant. The tissue levels of progesterone, estradiol and testosterone were much higher than the serum levels, whereas RU 486 concentration in the tissue was only one-third of the serum level. In addition, the RU 486 level in decidual cytosol was of the same order as that of progesterone. This competitive concentration was not achieved in chorionic villi in our previous observation, explaining why mifepristone exerts its predominant effect on decidua rather than villi. It is concluded that RU 486 reached an effective inhibitory concentration in decidua and had significant effects on the endocrine milieu. PMID- 8200220 TI - Antichlamydial activity of cervical secretion in different phases of the menstrual cycle and influence of hormonal contraceptives. AB - Cervical secretion from three groups of asymptomatic women, either being oral contraceptive (OC) non-users or users (ethinylestradiol plus desogestrel or levonorgestrel), was tested for its capacity to prevent Chlamydia trachomatis, serotype I, from forming inclusions in cycloheximide-treated McCoy cells. The non user groups were comprised of 12 women from whom cervical secretion was collected twice weekly during the menstrual cycle and 15 women from whom cervical secretion was collected once or twice weekly. The OC users included 66 women from whom cervical secretion was collected once or twice during their menstrual cycle. Cervical secretion from the non-users produced a decrease in the chlamydial inclusion count by 70%-90% during the first 3 weeks of the menstrual cycle, as compared with the fourth and fifth week when the reduction was 56%-68% (p < 0.001). Secretion from the OC users showed a more effective decrease in the inclusion count during the first 3 weeks of the menstrual cycle, as compared with samples obtained at the fourth and fifth weeks, i.e. 15%-35% vs. 20%-25% (p < 0.001). Cervical secretion of the non-users as compared to the users produced a significant decrease in the inclusion count, viz. 70%-90% vs. 15%-35% (p < 0.001) during the first 3 weeks as compared with 56%-68% vs. 20%-25% (p < 0.001) in the fourth or fifth week. The study suggests that natural resistance to genital chlamydial infection can differ during the menstrual cycle and it may be influenced by oral contraceptive use. PMID- 8200219 TI - Systemic availability of levonorgestrel after single oral administration of a norgestimate-containing combination oral contraceptive to 12 young women. AB - Norgestimate is a novel progestin which undergoes both in vivo and in vitro metabolic conversions to a number of metabolites, of which the most important are levonorgestrel acetate, levonorgestrel oxime and levonorgestrel itself. It has been claimed that the progestogenic activity of norgestimate in clinical studies is almost exclusively based on the parent drug and its major metabolite, levonorgestrel oxime, and that levonorgestrel does not make an important contribution. However, to date, no data on the presence of levonorgestrel in the serum of women who have received oral doses of norgestimate have been presented. In the present study, 12 young female volunteers received single oral doses of 250 micrograms levonorgestrel in combination with 50 micrograms ethinylestradiol and 250 micrograms norgestimate in combination with 35 micrograms ethinylestradiol in an open, randomized, intraindividual comparison. Blood samples were taken at regular time intervals after each treatment, and the serum samples were analyzed for their content of levonorgestrel. Basic pharmacokinetic parameters of levonorgestrel were calculated and from the ratio of the AUC values obtained after both administrations, the bioavailability of norgestimate-derived levonorgestrel was calculated. About 22 +/- 6% of the dose of norgestimate administered became systemically available as levonorgestrel. Thus, it was concluded that levonorgestrel is a major metabolite of orally administered norgestimate, and that at least part of the pharmacologic activity of norgestimate in women is due to the presence of levonorgestrel. PMID- 8200222 TI - A dermatologic diary. Portrait of a practice. PMID- 8200221 TI - Comparative progestational and androgenic activity of norgestimate and levonorgestrel in the rat. AB - The androgenic and the progestational activity of norgestimate (NORG) and levonorgestrel (LNG) were compared in two animal studies. During a Hershberger test in immature castrated male rats and a pregnancy maintenance test in pregnant rats, NORG and LNG were administered subcutaneously at several doses, serum samples were collected from each animal during the treatment period and the concentration of LNG was measured in these samples. It could be shown in both studies that in those animals which were treated with NORG, LNG was a major metabolite present in the serum. The difference in the pharmacological response in LNG- and NORG-treated rats was equivalent to the difference in the exposure of the animals to either directly administered or metabolically derived LNG. This was true for the androgenic and the progestational activity of NORG. It is concluded that according to the present results, NORG can be described as a pro drug of LNG and that the latter is probably mainly responsible for the pharmacological effects observed during treatment with NORG. It cannot be excluded, however, that NORG itself or other metabolites of this drug may also contribute to the pharmacodynamic response. PMID- 8200223 TI - Reducing the pain of local anesthesia. AB - The administration of local anesthetic agents before cutaneous surgery usually results in discomfort. This paper reviews techniques and pharmaceutical agents that will minimize pain during this preoperative procedure. PMID- 8200224 TI - Basic cutaneous surgery. AB - Basic surgical procedures are an integral part of the practice of dermatology. Instruction in basic cutaneous surgery is required of dermatology residency programs, and surgical procedures occupy a significant portion of the practicing dermatologist's time. This paper reviews the basic surgical techniques of fusiform excision, electrosurgery, cryosurgery, and curettage and briefly mentions the use of chemical destruction as it relates to these modalities. These techniques provide the basis for treatment of a multitude of benign and malignant lesions. Familiarity with the use, indications, and contraindications of each technique allows the appropriate choice of treatment for a given lesion, to ensure optimal outcome and minimize the chance of complications. PMID- 8200225 TI - Cosmetic procedures we all perform. AB - Dermatologic surgery has always been an integral part of dermatology. Over the past two decades, the scope of dermatologic surgery has greatly expanded to include procedures more traditionally thought of as cosmetic surgery, such as hair transplantation, liposuction, sclerotherapy, or soft tissue augmentation (Zyderm, Zyplast, Fibrel). Also, many dermatologic surgeons are expertly trained to reconstruct large surgical defects with flaps and skin grafts. Although these complex procedures are becoming synonymous with dermatologic surgery, procedures such as "simple" excision, electrosurgery, cryosurgery, curettage, or scissors surgery remain extremely important. These basic procedures are utilized daily in the office to treat a wide variety of skin lesions that may have a cosmetic or reconstructive aspect to them. PMID- 8200226 TI - Fundamentals of flap and graft wound closure in cutaneous surgery. AB - Optimal closure of cutaneous defects with flaps and grafts requires an understanding of the dynamics of tissue movement. The best cosmetic outcome is attained when all closure options are considered and the one most suitable for a given defect is chosen. The mnemonic "STARS" provides a convenient way to recall and consider all closure options. The basic principles and some practical considerations of these closure options are reviewed to assist in the understanding of the fundamentals of flap and graft wound closure in cutaneous surgery. PMID- 8200227 TI - Laser: when is it helpful, unequivocal, or simply a marketing tool. AB - Since lasers were first used for dermatologic applications in the early 1960s, they have continued to evolve as part of standard dermatologic practice. Initially, lasers were received enthusiastically but have since waxed and waned in popularity. I review the history of lasers and the differences between the common clinically applicable laser systems. Lasers have added a substantial dimension to our practice but have also been fraught with overuse. In an era of cost containment and health care reform, we need to consider the appropriate part lasers should play in dermatologic practice. PMID- 8200228 TI - Advanced cosmetic procedures. AB - Dermatology has changed in the past two decades. Surgery was always a part of the specialty of dermatology, including punch biopsies, minor excision, electrocautery, and other procedures. Mohs chemosurgery made a major impact on the management of all forms of skin cancer in the 1970s and 1980s. PMID- 8200230 TI - Fulminant amebic colitis. A morphologic study of four cases. AB - PURPOSE: The morphologic features of fulminant amebic colitis are poorly documented. In this report, we describe the clinical and pathologic findings in four of these cases. METHODS: The surgical pathology reports and accompanying histologic slides were examined from four patients who underwent surgical resections for fulminant amebic colitis. Clinical information was obtained from the patients' medical records. RESULTS: Large, geographic mucosal ulcers were typically present and were accompanied by yellow-green pseudomembranes. The muscularis externa was usually attenuated and necrotic, imparting a "wet blotting paper" consistency. Large numbers of amebic trophozoites were present within the inflammatory exudates. The mucosa adjacent to and undermined by the ulcers was often hemorrhagic or inflamed, resembling ischemic colitis or idiopathic inflammatory bowel disease, respectively. Two patients died within four weeks of their surgery. A third patient died one year later as a result of AIDS-related complications. The remaining patient has been lost to follow-up. CONCLUSION: An uncommon but life-threatening manifestation of intestinal amebiasis is a fulminant colitis. Early surgical intervention and intensive antiamebic chemotherapy are essential for efficacious management. PMID- 8200229 TI - Relationship among p53, stage, and prognosis of large bowel cancer. AB - PURPOSE: We designed a study to determine whether increases in p53 protein in primary carcinomas of the colon or rectum correlate with overall survival. Mutations of the tumor suppressor gene p53 are detectable by immunocytochemical methods in colorectal cancers because of accumulation of nuclear p53 protein. METHODS: IgG1 monoclonal antibody to human p53 protein (PAb 1801) was used to detect p53 in formalin-fixed, paraffin-embedded archival tumors resected from 84 patients with tumor limited to the bowel wall. A multivariate analysis was performed using five prognostic pathobiologic variables compared with the level of staining of the p53 product. RESULTS: Nuclear p53 protein was observed in 52 (62 percent) of 84 colorectal cancer patients with Stage T2 or T3, N0, M0 disease. Patients with strong expression (3+ and 4+) of p53 appeared to die from their disease sooner than those with weak expression (1+ and 2+), although this was not statistically significant (P > 0.59). Thirty-two patients did not express nuclear p53 by immunocytochemical methods. When these patients were analyzed in combination with the strong p53 expressors, the trend toward decreased survival increased (P > 0.15). CONCLUSIONS: This data suggest that lack of p53 expression may also predict an adverse outcome in colorectal cancer. However, before the immunocytochemical method can be used clinically as a prognostic indicator, the colorectal cancer patients with zero expression should be studied further to clarify the functional status of p53 in their tumors. PMID- 8200231 TI - Proliferative activity at colonic anastomoses as determined by statin. A nonproliferation-specific nuclear protein. AB - PURPOSE: One theory of anastomotic recurrence in large bowel carcinoma is that epithelial hyperplasia at the suture line causes metachronous carcinoma. METHODS: S44, a monoclonal antibody directed against statin, a nuclear protein expressed in quiescent cells, was used to determine whether the anastomosis represents an area with a high proliferation rate. During follow-up colonoscopic examination of patients who had undergone previous resection for colorectal carcinoma, biopsies were taken from the anastomotic site and from the mucosa 10 to 15 cm from the anastomosis. One side of 10 well-oriented crypts was counted for each patient with the number of nuclei positive for statin being determined by the presence of dark brown reaction product. RESULTS: The average percentages of statin-positive cells varied between 19.4 and 44.4 (average, 31.3 +/- 6.5) for the normal mucosa and 22.8 to 35.1 (average, 29.98 +/- 3.67) for the anastomotic mucosa. The differences were not significant. There were no differences between those patients in whom the postoperative time elapsed was two years or less and those greater than two years. CONCLUSION: This study is unique in that the proliferative activity at the site of colonic anastomosis was determined in a clinical setting, and patients in which the anastomoses were created anywhere from 1 to 14 years earlier were included. Using S44 as a marker, this study does not support the theory that suture line recurrence is a result of an enhanced proliferation rate. PMID- 8200232 TI - Reliability and validity studies of endoluminal ultrasonography for anorectal disorders. AB - PURPOSE: Endoluminal ultrasonography (ELUS) is accurate in the assessment of penetration through the rectal wall by carcinoma. Clinical studies were performed to determine the reliability and validity of ELUS. METHODS: The interobserver reliability among four observers with varying experience with ELUS was determined for staging the penetration of rectal cancer through the rectal wall. The ability of ELUS to change the clinical management of the referring clinician (comprehensiveness) was assessed on all referrals over a six-month period. RESULTS: The reliability of ELUS for staging rectal cancer demonstrated only fair to moderate correlation (weighted kappa range, 0.22-0.47). The accuracy of ELUS compared with surgical pathology demonstrated a learning curve proportional to the experience of the observer. In 45 percent of referrals, ELUS changed the clinical management of patients and in 76 percent of referrals the clinician's confidence in the diagnosis and management of patients was altered. ELUS was more likely to change the management of patients with pelvic pouch sepsis (70 percent) and early neoplastic lesions (57 percent) than in more advanced neoplastic lesions (40 percent), perianal Crohn's disease (40 percent), complex noninflammatory bowel disease sepsis (33 percent), and incontinence (31 percent). CONCLUSIONS: ELUS has the ability to change the clinical management of a variety of anorectal conditions. However, for neoplasia the interobserver reliability is only moderate and a learning curve exists. PMID- 8200233 TI - Laparoscopic oncologic abdominoperineal resection. AB - PURPOSE: Although the use of laparoscopic techniques in colorectal surgery has recently become a focus of major interest in intestinal surgery, there is no proof that an oncologic abdominoperineal resection can be accomplished using laparoscopic techniques. The hypothesis of this study is that a standardized technique for laparoscopic oncologic abdominoperineal resection according to accepted oncologic surgical principles can be developed in a cadaver model. The end points of this study were intraoperative complications, success in performance of proximal vascular ligation of the inferior mesenteric artery, complete removal of the mesorectum including all lymph nodes adjacent to the named rectal arteries, and wide clearance of pelvic side walls. METHODS: Laparoscopic abdominoperineal resection was performed in 11 fresh cadavers (1 female and 10 males). After surgery, all cadavers underwent autopsy. The number of removed and remaining mesenteric lymph nodes, length of remaining inferior mesenteric artery, and mesorectal and the pelvic side wall soft tissue were evaluated. RESULTS: No major intraoperative complications were recorded. The median number of removed lymph nodes in the mesorectum was 12 (range, 6-22) and no remaining lymph nodes were found at the base of the inferior mesenteric artery. The median length of remaining inferior mesenteric artery was 5 (range, 1 15) mm. Wide lateral clearance of pelvic side walls was noted in all patients. CONCLUSION: A laparoscopic technique of abdominoperineal resection can be performed according to oncologic principles with proximal vascular ligation of inferior mesenteric artery, wide clearance of pelvic side walls, and complete removal of mesorectum using our described technique. PMID- 8200234 TI - National guidelines for enterostomal patient education. Prepared by the Standards Development Committee of the United Ostomy Association with the Assistance of Prospect Associates. PMID- 8200235 TI - Simplified solid sphere test to investigate anal sphincter strength in patients with anorectal diseases. AB - PURPOSE: The solid sphere test has not gained general acceptance to investigate anal sphincters, despite its simplicity and low cost. We studied continent and incontinent patients to evaluate whether the solid sphere test is suitable in assessment of anal sphincter function. METHODS: Seventy colorectal patients with anal incontinence of varying severity were studied by means of incontinence grading, solid sphere test, and anal manometry. RESULTS: Anal sphincter strength, studied using the solid sphere test, declined gradually with increasing severity of anal incontinence from 1,186 (+/- 334, SD) g in 28 continent patients to 619 (+/- 256, SD) g in 13 patients with daily soiling (P < 0.001). The test also correlated with anal manometry; there was positive correlation with maximum basal pressure (r = 0.643, P < 0.001) and maximum voluntary contraction pressure (r = 0.393, P < 0.01). CONCLUSION: The solid sphere test is useful in the primary assessment of patients with anal incontinence as a screening test, but alone it is too inaccurate for clinical decision making. PMID- 8200236 TI - Colonoscopic follow-up of colorectal carcinoma. AB - PURPOSE: The value of routine colonoscopy in the prevention or early detection of metachronous carcinoma of the colon and rectum remains unproven. This study attempts to clarify this issue. METHODS: An analysis of a personal series of 460 patients with primary colorectal carcinoma treated by the second author between 1972 and 1990 was reviewed. After various exclusions, there remained 231 patients who had been prospectively followed by colonoscopy with a mean follow-up period of 5.6 years. RESULTS: In 48 (21 percent) patients, there were synchronous adenomas present at the time of the initial resection for carcinoma and 35 (73 percent) of these patients subsequently developed metachronous adenomas, being recurrent in 22. Ninety-five (52 percent) of the 183 patients without synchronous adenomas eventually developed metachronous adenomas, so that overall 130 (56 percent) patients developed a metachronous adenomas. Four patients developed a metachronous carcinoma that was either Dukes A or B, and all remain well at the time of final follow-up. These metachronous carcinomas were found after a mean interval of seven and three-quarter years. All four patients had synchronous adenomas and all developed metachronous adenomas on multiple occasions before the metachronous carcinoma was detected. Thus, a subset consisting of only 22 patients produced all four metachronous malignancies--a rate of 18 percent. CONCLUSION: It would appear that the presence of synchronous adenomas with the subsequent development of recurring metachronous adenomas is significant and warrants a more intensive follow-up program to ensure the early diagnosis and more likely cure of any metachronous carcinoma. PMID- 8200237 TI - Current follow-up strategies after resection of colon cancer. Results of a survey of members of the American Society of Colon and Rectal Surgeons. AB - The follow-up of patients after potentially curative resection of colon cancer has important clinical and financial implications for patients and society, yet the ideal surveillance strategy is unknown. PURPOSE: The aim of this study was to determine the current follow-up practice pattern of a large, diverse group of experts. METHODS: The 1,663 members of The American Society of Colon and Rectal Surgeons were asked, via a detailed questionnaire, how often they request nine discrete follow-up evaluations in their patients treated for cure with TNM Stage I, II, or III colon cancer over the first five posttreatment years. These evaluations were clinic visit, complete blood count, liver function tests, serum carcinoembryonic antigen (CEA) level, chest x-ray, bone scan, computerized tomographic scan, colonoscopy, and sigmoidoscopy. RESULTS: Forty-six percent (757/1663) completed the survey and 39 percent (646/1663) provided evaluable data. The results indicate that members of The American Society of Colon and Rectal Surgeons generally conduct follow-up on their patients personally after performing colon cancer surgery (rather than sending them back to their referral source). Routine clinic visits and CEA levels are the most frequently performed items for each of the five years. The large majority (> 75 percent) of surgeons see their patients every 3 to 6 months for years 1 and 2, then every 6 to 12 months for years 3, 4, and 5. Approximately 80 percent of respondents obtain CEA levels every 3 to 6 months for years 1, 2, and 3, and every 6 to 12 months for years 4 and 5. Colonoscopy is performed annually by 46 to 70 percent of respondents, depending on year. A chest x-ray is obtained yearly by 46 to 56 percent, depending on year. The majority of the members of The American Society of Colon and Rectal Surgeons do not routinely request computerized tomographic scan or bone scan at any time. There is great variation in the pattern of use of complete blood count and liver function tests. Members of The American Society of Colon and Rectal Surgeons from the United States tend to follow their patients more closely than do those living in other countries. The intensity of follow-up does not markedly vary across TNM Stages I to III. CONCLUSION: The surveillance strategies reported here rely most heavily on clinic visits and CEA level determinations, generally reflecting guidelines previously proposed in the current literature. PMID- 8200238 TI - Must early postoperative oral intake be limited to laparoscopy? AB - PURPOSE: This prospective, randomized study was designed to evaluate whether or not early postoperative feeding (claimed as a unique benefit of laparoscopic surgery) is possible after laparotomy and colorectal resection. METHODS: The trial was performed between July 1, 1992 and October 31, 1992 and included all 64 consecutive patients who underwent laparotomy with either a colonic or an ileal resection. In all cases the nasogastric tube was removed immediately after the operation. Group 1 consisted of 32 patients (age range, 15-81 years; mean, 52 years) who received a regular diet on the first postoperative morning. Group 2 consisted of 32 patients (age range, 15-87 years; mean, 52 years) who were fed in a traditional manner. Regular food was permitted after resolution of ileus as defined by resumption of bowel movements in the absence of abdominal distention, nausea, or vomiting. RESULTS: The rate of nasogastric tube reinsertion for distention with persistent vomiting was 18.7 percent (six patients) in Group 1 and 12.5 percent (four patients) in Group 2. Although vomiting was experienced more frequently by patients in Group 1 (44 percent vs. 25 percent, respectively), there was no difference between the two groups with regard to the duration of postoperative ileus (3.6 vs. 3.4 days, respectively). In the 26 patients from Group 1 who did not require nasogastric tube reinsertion, there was a trend toward shorter hospitalization (6.7 vs. 8.0 days, respectively). CONCLUSION: Early oral intake is possible after laparotomy and colorectal resection. Thus, the laparoscopic surgeon's claim of early tolerated oral intake may not be unique to laparoscopy. PMID- 8200239 TI - Effect of electrostimulation on sphincter function in neurogenic fecal continence. AB - PURPOSE: This study was designed to examine the effects of electrostimulation on sphincter function. METHODS: Electric stimulation was performed twice a day for 30 minutes over a 12-week period on 10 patients with neurogenic fecal incontinence. Anal manometry was repeated after 6 and 12 weeks. RESULTS: Two patients experienced some improvement. Mean resting pressure was increased by 0.6 (-5.8 to +5.3) kPa and mean squeezing pressure by 0.3 (-1.6 to +2.6) kPa. All values remained below continent levels. An increase in squeezing pressure after both 6 and 12 weeks was recorded in only one patient. CONCLUSION: Electrostimulation does not improve internal or external sphincter function. There is no indication that it will do so in the long term either. PMID- 8200241 TI - Pitfall of laparoscopic colectomy. An unrecognized synchronous cancer. AB - This case report describes near-obstructing sigmoid colon cancer resected using the laparoscopic-assisted technique. An unrecognized, synchronous cecal cancer caused an early postoperative bowel obstruction. The authors review the incidence of synchronous colon lesions and the need for preoperative and intraoperative evaluation of the entire colon, especially with the use of the laparoscopic technique. PMID- 8200240 TI - Evidence of electromechanical dissociation of the internal anal sphincter in idiopathic fecal incontinence. AB - PURPOSE: This study was designed to evaluate the relationship between internal sphincter electromyographic frequency and ambulatory anal pressures in order to clarify the pathophysiology of internal anal sphincter dysfunction in fecal incontinence. METHODS: Seventy-two patients of median age 55 years (range, 24-75; 63 females) with neurogenic fecal incontinence and 33 normal subjects of median age 48.5 years (range, 25-74; 21 females) underwent fine-wire anal sphincter electromyography and anal manometry. RESULTS: The median internal anal sphincter electromyographic frequency was incontinent 0.25 Hz (0.2-0.34) and the control was 0.44 Hz (0.36-0.55; P < 0.03). Ambulatory resting pressures were incontinent median 54 cm of H2O (34-68 cm of H2O) and control 94 cm of H2O (72-102; P < 0.01). Internal sphincter electromyographic frequency correlated with anal resting pressures in both groups (P < 0.002). Internal sphincter electromyographic silence not attributable to electrode movement or the rectoanal inhibitory reflex, lasting 0.5 to 4 minutes occurred in all but two of the incontinent patients. The anal pressure during this period did not significantly change (P > 0.1). No recruitment of the external sphincter or puborectalis was noted during these episodes. Such electromechanical dissociation was not seen in the control group. The frequency of transient internal sphincter relaxation was 4 (ranges 2-6) per hour in controls and 8 (ranges, 6-12) per hour in incontinent patients (P < 0.01). Rectal pressures did not exceed midanal pressures in any of the controls but did in all of the incontinent patients on at least one occasion per hour in the incontinent group. CONCLUSION: Internal anal sphincter activity exhibits electromechanical dissociation and relaxes abnormally in incontinent patients. PMID- 8200242 TI - Modified technique for handsewn anastomosis following abdominoperineal pull through operation. AB - A modified technique for handsewn anastomosis after abdominoperineal pull-through resection is described. The technique is a continuous locked modification of the Gambee suture. Simplicity, rapidity, reliability, and firmness are the advantages of this technique. PMID- 8200243 TI - Construction of a new intestinal valve. AB - PURPOSE: A surgical technique is presented which creates an intestinal valve. METHODS: In six dogs, the terminal ileum and the ascending colon were removed and the valve was made. The valve has been constructed in eight humans, three of them were cases of short bowel syndrome with resection of the ileocecal valve and five cases were right hemicolectomies attributable to a carcinoma of the cecum and ascending colon. RESULTS: The dogs were observed for a period of four to six months, during which time the animals stayed healthy. In the cases of short bowel syndrome in humans, the valve reduced the number of evacuations, in the five cases of right hemicolectomies the evolution was without complications. CONCLUSION: This surgical technique can be useful in the management of patients with morbidity by resection of the ileocecal valve. PMID- 8200244 TI - Current surgical therapy for mucosal ulcerative colitis. AB - PURPOSE: There are numerous surgical options for the treatment of mucosal ulcerative colitis. METHODS: This article reviews the currently available options for the treatment of mucosal ulcerative colitis. Separate discussions will explore both the options in the emergency and elective settings. RESULTS: Patients with mucosal ulcerative colitis may undergo surgery either as an emergency or in the elective setting. Emergency surgery is usually performed for one of the life-threatening complications of ulcerative colitis: fulminant colitis, toxic megacolon, or massive hemorrhage. The most commonly performed procedure under these conditions is a subtotal colectomy with end ileostomy. The rectal stump may be handled in a variety of ways. This procedure avoids proctectomy or anastomosis. Thus, patients will still have all necessary anatomic structures to allow for any of the definitive elective procedures. Elective surgery is performed for intractable disease, complications of medical therapy, dysplasia, or, occasionally, extraintestinal manifestations. In the elective setting, a definitive operation can be done to remove most or all of the disease bearing colorectum and leave the patient with a means to control fecal elimination. Total abdominal colectomy with ileorectal anastomosis leaves the patient with diseased bowel but obviates the need for pelvic dissection. Although total proctocolectomy removes all potentially diseased mucosa, these patients have a permanent ileostomy. The stoma can either be a standard Brooke's ileostomy or a continent Kock pouch. The most common definitive procedure currently performed is the near-total proctocolectomy with ileal pouch-anal anastomosis. This option can be completed either with a rectal mucosectomy and hand-sewn anastomosis or with a double-stapled anastomosis, preserving the anal transition zone. This procedure is successful in eradicating almost all diseased mucosa while allowing the patient per anal defecation. Bowel movement frequency, degree of anal continence, and return to social and professional commitments have met with a great deal of satisfaction in most patients. A newer alternative to this procedure employs laparoscopy to facilitate a smaller incision. A one-stage procedure which omits the protective ileostomy and thus saves the patient one operation has also been used with some success in selected cases. CONCLUSION: There are several surgical options for the treatment of mucosal ulcerative colitis. Each one has a role and should be discussed with the patient. PMID- 8200245 TI - Concerns about laparoscopic colon cancer surgery. PMID- 8200246 TI - Efficacy of leuprolide in treatment of the irritable bowel syndrome. PMID- 8200248 TI - Effect of leuprolide acetate in patients with functional bowel disease. Long-term follow-up after double-blind, placebo-controlled study. AB - We initially investigated the effects of a gonadotropin-releasing hormone analog, leuprolide acetate, in 28 patients with moderate to severe functional bowel disease in a phase-II, randomized, double-blind, and placebo-controlled study using Lupron Depot 3.75 mg (which delivers a continuous low dose of drug for one month) or placebo given intramuscularly. After completing that 12-week study period during which their symptoms had improved significantly (P < 0.01-0.5), the 28 patients were allowed to continue receiving leuprolide acetate; they were monitored for an additional 40 weeks. Of those 28, 25 (89%) finished the 52-week treatment. Drug administration was changed from the monthly low-dose form of leuprolide acetate to a daily subcutaneous dose that was gradually increased from 0.5 mg daily to an effective therapeutic dose (1.0-1.5 mg). All subjects received estrogen replacement during this period. Continued use of leuprolide acetate at maximum therapeutic dosage and over longer periods of time produced even more striking and significant changes in the disabling and debilitating symptoms of functional bowel disease. Nausea, abdominal pain, early satiety, anorexia, and abdominal distension decreased markedly (P < 0.0001) and vomiting was also reduced (P < 0.01) more than in the short-term, low-dosage, double-blind study. Combined total symptom scores and overall assessment also changed significantly in the long-term phase (both P < 0.0001). PMID- 8200247 TI - Effect of leuprolide acetate in patients with moderate to severe functional bowel disease. Double-blind, placebo-controlled study. AB - Moderate to severe functional bowel disease results in debilitating abdominal pain, nausea, intermittent vomiting, early satiety, bloating, abdominal distension, and/or altered bowel habits. Because it occurs approximately 20-30 times more frequently in women than in men and its symptoms often coincide with the menstrual cycle, we hypothesized that reproductive steroids may antagonize diseased nerves of the gastrointestinal tract, enhancing the expression of symptoms. No effective or consistent therapy has existed for these patients. We prospectively investigated the effect of a gonadotropin-releasing hormone analog, leuprolide acetate, in 30 women with symptoms of moderate to severe functional bowel disease. The study was phase II, randomized, double blind, and placebo controlled. Lupron Depot 3.75 mg (which delivers a continuous low dose of drug for one month) or placebo were given intramuscularly monthly for three months. Symptom scores were assessed at each four-week visit. Follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone levels were assessed before and after therapy. Patients treated with low-dose leuprolide improved progressively and significantly in scores for nausea, vomiting, bloating, abdominal pain, and early satiety, and for overall symptoms (P < 0.01-0.05). All hormone levels decreased significantly (P < 0.05) except luteinizing hormone (P = 0.054). PMID- 8200249 TI - Octreotide increases thresholds of colonic visceral perception in IBS patients without modifying muscle tone. AB - Effects of octreotide (1.25 micrograms/kg subcutaneously) on colonic tone and visceral perception were evaluated in 10 IBS patients, using a barostat and compared to placebo in a double-blind crossover study. Colonic sensory thresholds were also studied in healthy controls for comparison with IBS patients. Colonic tone was reflected by variations in volume of the barostat balloon. Baseline volume was 117 +/- 38 ml and was not modified by placebo (122 +/- 40 ml) or octreotide (106 +/- 42 ml). After the meal, maximal decrease in balloon volume was 75 +/- 4% following placebo (P < 0.001) beginning after 9 +/- 3 min and lasting 136 +/- 17 min. Following octreotide, the maximal decrease was 69 +/- 16% (NS vs placebo), after 10 +/- 3 min and lasting 140 +/- 22 min. In the second part, discomfort and pain thresholds were evaluated during isobaric distensions (4 mm Hg increments, 5-min duration, 5-min interval with return to pressure 0 between each). The pressure inducing discomfort was 21.2 +/- 5.9 mm Hg following placebo vs 29.6 +/- 6.6 mm Hg following octreotide (P < 0.01). The pressure inducing pain was 24.8 +/- 7.3 mm Hg following placebo vs 33.2 +/- 7.3 mm Hg following octreotide (P < 0.01). In healthy subjects, discomfort and pain were induced by colonic distensions at a mean intraballoon pressure of 32.7 +/- 5.8 mm Hg and 36.7 +/- 3.9 mm Hg, respectively. Compliance curves were not different following placebo and octreotide. Octreotide significantly increases thresholds for visceral perception in IBS patients without modifying compliance during distension nor colonic tone. PMID- 8200250 TI - Double-blind crossover trial of metronidazole versus placebo in chronic unremitting pouchitis. AB - Metronidazole has been used to treat pouchitis, but there are no controlled data that show it is effective. Chronic unremitting pouchitis is a form of the disorder particularly difficult to manage. Diarrhea is the main symptom of pouchitis, which results from acute inflammation of the mucosa of an ileal reservoir. To test the hypothesis that metronidazole (400 mg thrice daily for seven days) is no better than placebo at reducing stool frequency in chronic unremitting pouchitis, a double-blind placebo-controlled crossover study has been performed. Thirteen patients who had undergone restorative proctocolectomy for ulcerative colitis were studied. The diagnosis of pouchitis was based on clinical, endoscopic, and histological criteria. At entry all patients had symptomatic pouchitis and were passing more than six stools/24 hr or had consistently bloody stools with at least four of six endoscopic criteria of mucosal inflammation. The median frequency of defecation decreased by 3 bowel actions/24 hr (conservative 95% confidence intervals 0-4/24 hr) on metronidazole but increased by a median of 1/24 hr on placebo. The difference between the median number of bowel motions, when treatment with metronidazole was compared to placebo, was 4 motions/24 hr (P < 0.05) in favor of metronidazole. There was no significant change in the endoscopic or histological grade of inflammation, in the serum C-reactive protein level, or symptomatic scores. In a parallel study, metronidazole did not alter stool frequency in asymptomatic patients without pouchitis who had endoscopically normal reservoirs (six polyposis, six colitis).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200251 TI - Endothelial proliferation in experimental granulomatous colitis. Autoradiography and immunohistochemistry studies. AB - The time sequence and magnitude of endothelial cell proliferation was investigated in an experimental model of granulomatous colitis in rats, induced by intramural inoculations of mycobacterium Bacillus Calmette-Guerin. Colonic tissues were assessed by gross examination, histopathology, autoradiography, and immunohistochemistry. Gross examination of the colonic tissue showed thickening of the colonic wall, erythema, hemorrhage, and scattered ulcers. Histopathological findings were characterized by an acute transmural inflammation, progressing to chronic inflammation accompanied by regenerative changes in the glandular epithelium, goblet cell depletion, mucosal atrophy and fibrosis. Well-developed noncaseating granulomas were first observed at day 5 and were found to be a dominant feature up to day 17. Autoradiographic studies showed increased endothelial cell labeling up to 17% at 48 hr, compared to less than 1% labeling in control animals. Immunostaining for factor VIII-related antibody, an endothelial cell marker, showed increased numbers of microvessels and individual positive cells located in areas of inflammation as early as 24 hr. At day 5 these individual cells along with dilated neocapillaries were found surrounding the granulomas. This model of granulomatous colitis mimics many features of the human disease state. The early increase in endothelial cell proliferation that precedes granuloma formation during the course of the inflammatory response may suggest that the events leading to the expression of granulomatous colitis are dependent on endothelial proliferation. PMID- 8200253 TI - Myoelectric activity during small bowel allograft rejection. AB - The effect of rejection on myoelectric activity of an orthotopically transplanted small intestinal segment (group I, N = 14) was studied. Electrodes were placed on grafts and recipient small bowel. Isografts (group II, N = 5) and native bowel (group III, N = 5) served as controls. The first morphological signs of rejection were seen on day 6 and steadily progressed until day 11, when the cellular infiltrate involved all layers of the bowel wall. Slow-wave frequencies remained unchanged throughout the observation period. No difference was detectable between grafts (group I: 31.9 +/- 1.65; group II: 31.36 +/- 0.7) and native bowel after transection (group I: 32.16 +/- 1.78; group II: 31.50 +/- 1.01), which was different (P = 0.0001) from intact bowel of group III animals (38.4 +/- 0.81). Irregular MMCs were detectable in grafts from day 5 on and replaced after food intake by random spiking activities. At day 8, spiking activities disappeared in allografts, which showed a still preserved mucosal architecture, while slow-wave activities continued. These findings demonstrate that intestinal allografts during rejection develop paralysis before mucosal destruction is established, which might be of clinical relevance. PMID- 8200252 TI - Experimental colitis in rats induces low-grade endotoxinemia without hepatobiliary abnormalities. AB - In three experimental models in rats, surgical construction of a self-filling blind loop (SFBL), trinitrobenzene sulfonic acid (TNB) -induced colitis, and the combination of SFBL and TNB, the hypothesis was studied that intestine-derived endotoxins play a role in the pathogenesis of hepatobiliary disorders in chronic inflammatory bowel disease (CIBD). After eight weeks of treatment, a mild increase in portal and systemic endotoxin levels and interleukin-6 concentrations was observed and the serum levels of alkaline phosphatase, bilirubin, and ALAT were only mildly increased in SFBL plus TNB rats. Histopathological examination of the liver showed hardly any abnormalities in all three rat models. These results show that low-grade portal and systemic endotoxinemia in rats, induced by bacterial overgrowth and/or chemical colitis, is not able to induce hepatobiliary alterations. To exclude definitively a possible role for portal endotoxinemia in the pathogenesis of CIBD-associated hepatobiliary abnormalities, however, an adequate animal model for CIBD is urgently needed. PMID- 8200254 TI - Effects of artificial ileocolonic sphincter on motility in intestinal remnant following subtotal small intestinal resection in the dog. AB - We studied the effects of a sphincter substitute on motility in the intestinal remnant following an extensive distal intestinal resection. Two groups of adult dogs were studied; each underwent a 75% resection of the distal small intestine, and in one group a nipple valve was fashioned at the distal end of the remnant. Nutritional status, absorptive function, motility, and transit were studied over a three-month period. While the nipple valve animals had less diarrhea, steatorrhea, and hypoalbuminemia, motor activity and transit were similar in both groups. Thus, in both groups, fasting motor activity was dominated by clusters of phasic pressure activity. (Cluster frequency, per hour, mean +/- SE, resection vs resection with nipple valve: 4.8 +/- 1.05 vs 3.58 +/- 0.54, NS). We conclude that the beneficial effects of a sphincter substitute in ameliorating the short bowel syndrome in this dog model are not related to any modification of the motor response to resection but may simply reflect those of a low-grade mechanical obstruction. PMID- 8200255 TI - Verotoxin induces hemorrhagic lesions in rat small intestine. Temporal alteration of vasoactive substances. AB - E. coli O157:H7 produces a cytotoxin active against Vero cells that has been termed verotoxin. In this study, we demonstrated that local intraarterial injection of verotoxin induced a decrease in blood flow and an increase in hemorrhagic lesions in rat small intestine. Significant increases in the area of hemorrhagic lesions were observed at 120 min after verotoxin injection. These lesions were produced by either verotoxin 1 or 2, but verotoxin 2 produced more extensive lesions. The temporal alteration of vasoactive substances in microcirculatory beds was determined after the administration of culture filtrate of E. coli O157:H7. Tissue-type plasminogen activator activity in regional plasma was significantly elevated as early as 30 min, suggesting that local fibrinolytic activation mediated by microvascular endothelium occurred. There was also early elevation of platelet-activating factor content in the ileal mucosa and its level remained significantly elevated thereafter. Intestinal blood flow, as determined by a laser Doppler flowmeter, started to decrease at about 45 min. The platelet activating factor antagonist CV6209 was shown to attenuate the decrease in blood flow as well as the development of hemorrhagic lesions, demonstrating that platelet-activating factor is an important mediator for the microcirculatory damage. Accumulation of neutrophils demonstrated by myeloperoxidase activity in the intestinal mucosa and overproduction of oxygen-radicals from neutrophils of the mesenteric veins determined by the luminol-dependent chemiluminescence assay were observed at 60 min, corresponding with the decreased blood flow. Platelet activating factor may be closely involved in the process of leukocyte accumulation and increased oxygen radical generation, because CV6209 also significantly attenuated these changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200256 TI - Experimental colitis alters visceromotor response to colorectal distension in awake rats. AB - The influence of intermittent colorectal distension (CRD) on proximal colonic motility and abdominal pain perception was investigated in awake rats equipped with intraparietal electrodes on the cecum, proximal colon, and abdomen, before and three days after rectocolitis induction by trinitrobenzene sulfonic acid (TNB)/ethanol. The normal myoelectrical activities of cecum and proximal colon [5.2 +/- 0.5 and 9.7 +/- 0.7 long spike bursts (LSB) per 5 min, respectively] were significantly (P < 0.05) and gradually decreased by control CRD, at diameters above 9 mm. At the maximum CRD diameter (13.7 mm), 1.6 +/- 0.6 cecal and 3.9 +/- 0.8 colonic spike bursts occurred per 5 min (respectively, 69 and 60% decreases). This upstream inhibition was accompanied by a significant (P < 0.05) and gradual increase in abdominal contractions (0.4 +/- 0.4 per 5 min in control vs 23.4 +/- 1.9 in response to 13.7 mm in diameter). Three days after TNB/ethanol, visceromotor and abdominal responses were significantly (P < 0.05) enhanced at the least CRD diameter of 9 mm (cecum: 3.1 +/- 0.4 after TNB vs 5.0 +/- 0.7 in control; proximal colon: 5.1 +/- 0.9 vs 9.3 +/- 2.2; abdomen: 7.7 +/- 1.5 vs 0.5 +/- 0.4). We conclude that in awake rats, CRD evokes both abdominal contractions in response to pain and inhibition of cecal and proximal colonic motility, which thresholds are both lowered by TNB-induced rectocolitis. PMID- 8200257 TI - Misoprostol protection against acetaminophen-induced hepatotoxicity in the rat. AB - The hepatoprotective effects of misoprostol on acetaminophen (APAP)-induced toxicity were studied in the rat. Liver injury was evaluated at 36 hr after APAP administration by measuring serum ornithine carbamoyltransferase (OCT) and alanine aminotransferase (ALT) levels, by using tetranitroblue tetrazolium (TNBT) staining and by histological analysis. After APAP administration, peak serum levels of the drug were detected at 15 min. Liver GSH was depleted from control levels of 448 +/- 48 micrograms/g to 82 +/- 2 micrograms/g (P < 0.01) within 3 hr. Serum ALT levels increased significantly after 16 hr and H&E staining revealed significant hepatic necrosis after 12 hr. Rats treated with misoprostol before and after APAP administration showed reduced OCT and ALT levels at 36 hr of overdose (454 +/- 446 IU/liter and 2571 +/- 2944 IU/liter, respectively) compared to those without misoprostol treatment (1348 +/- 480 IU/liter and 6077 +/- 3025 IU/liter, respectively, P < 0.01). TNBT staining showed a reduced area of damage from 28.6 +/- 22.3% to 7.3 +/- 8.9% (P < 0.01), and H&E staining also showed less extensive hepatic necrosis in rats treated with misoprostol before and after the overdose. In a time sequence study, misoprostol treatment starting within 10 hr of overdose showed the same protective effect as when it was given before and after APAP ingestion. No protection was detected when the treatment was started during the development of hepatic injury. However, misoprostol given when injury was established seemed to be protective. Our results show that misoprostol protects the liver against APAP-induced injury if given within 10 hr of overdose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200258 TI - Role of iron and glutathione redox cycle in acetaminophen-induced cytotoxicity to cultured rat hepatocytes. AB - The aims of this study were to investigate the roles of iron as a catalyst in reactive oxygen metabolite-mediated cellular injury and of the endogenous antioxidant defenses against acetaminophen-induced cytotoxicity in cultured rat hepatocytes. Hepatocytes were isolated and cultured from either 3 methylcholanthrene-treated or untreated rats. Cytotoxicity was evaluated by measuring 51Cr and lactate dehydrogenase release. Acetaminophen caused dose dependent cytotoxicity in 3-methylcholanthrene-treated, but not untreated, cells. There was a good correlation between 51Cr and lactate dehydrogenase release values. Pretreatment with both diethyl maleate, which covalently binds glutathione as catalyzed by glutathione-S-transferase, and bis(chloroethyl) nitrosourea, an inhibitor of glutathione reductase, enhanced acetaminophen induced cytotoxicity. Inhibition of endogenous catalase activity by pretreatment with aminotriazole did not affect acetaminophen-induced cellular damage. Addition of exogenous catalase failed to protect against acetaminophen-induced cytotoxicity. Preincubation with both deferoxamine, a ferric iron chelator, and phenanthroline, a ferrous iron chelator, diminished acetaminophen-induced cytotoxicity. These results indicate that iron is crucial in mediating acetaminophen-induced cytotoxicity and that the glutathione redox cycle, but not catalase, plays a critical role in the endogenous defenses against acetaminophen induced cellular damage in cultured rat hepatocytes in vitro. PMID- 8200259 TI - Modulation of ischemia-reperfusion-induced hepatic injury by Kupffer cells. AB - To elucidate the role of Kupffer cells in ischemia-reperfusion-induced hepatic injury, hepatic injury induced by ischemia-reperfusion was analyzed after modulation of Kupffer cell function. Ischemia of the liver was performed by occlusion of both the portal vein and hepatic artery, which enter into the left lateral and median lobes of the liver. Blood flow in the ischemic lobe was reduced, in contrast to an increased blood flow in the nonischemic lobe during occlusion of the veins. Although hepatocyte damage was not demonstrated by ischemia for < 60 min, hepatic injury was found after reperfusion of the liver, and activation of Kupffer cells was morphologically demonstrated by electron microscopies. Suppression of Kupffer cells, induced by previous administration of gadolinium chloride or latex particles, reduced the grade of hepatic injury induced by ischemia-reperfusion. On the other hand, stimulation of Kupffer cell phagocytosis, induced by administration of latex particles at the time of reperfusion, aggravated the ischemia-reperfusion-induced hepatotoxicity, which was then reduced by simultaneous administration of superoxide dismutase. Kupffer cells, isolated from the rats treated with the ischemia-reperfusion procedure, have been found to release increased amounts of oxygen radical intermediates. These results suggest that hepatic injury induced by ischemia-reperfusion is modulated by the function of Kupffer cells and that superoxide anion released from Kupffer cells could play an important role in ischemia-reperfusion hepatic injury. PMID- 8200260 TI - Viral and host factors that contribute to efficacy of interferon-alpha 2a therapy in patients with chronic hepatitis C. AB - Using conventional statistical analysis and multiple regression analysis, we investigated the viral and host factors that influence the response to recombinant interferon-alpha 2a therapy in patients with chronic hepatitis C. A total of 36 patients was randomly assigned to three administration schedules, 12 patients in each. Response to treatment was set as the criterion variable. Four variables were statistically significant in the conventional method in predicting a good therapeutic outcome: HCV genotype III and IV, lower histology activity index (HAI) score for liver, higher total dose of interferon administration, and lower serum HCV RNA concentration. In multiple regression analysis, a combination of the above four variables resulted in a higher multiple correlation coefficient (R = 0.84, P < 0.0001) using a stepwise method. Of those four, HCV genotype had the highest absolute value of standard partial regression coefficient (0.51). The HCV RNA concentration was correlated with HCV genotype and HAI score, whereas HCV genotype and HAI score showed no correlation. Thus, HCV RNA concentration was not statistically significant in multiple regression analysis. These findings indicate that HCV genotype, HAI score, and schedule of administration can be important predictors of the response to interferon therapy. PMID- 8200261 TI - Variations of hepatitis B virus precore/core gene sequence in acute and fulminant hepatitis B. AB - Variations of the hepatitis B virus (HBV) precore/core sequence has been shown to play a role in the development of active liver disease in chronic hepatitis B. Whether this is also an important viral factor in the pathogenesis of acute and fulminant hepatitis B is unknown. To determine the precore/core gene sequence in patients with acute and fulminant hepatitis B, 11 patients with fulminant hepatitis B and seven patients with acute hepatitis B were studied. The sequences of precore/core gene were determined by direct sequencing of the polymerase chain reaction amplicons generated from the HBV isolated from patients' serum. For the 11 patients with fulminant hepatitis B, the precore/core regions were successfully amplified in 10 patients. Eight patients exhibited precore stop codon mutations. In addition, nine of the 10 fulminant hepatitis B patients had frequent nucleotide substitutions with corresponding changes in the predicted amino acid sequences in the mid-core and the 5' terminus region of the core gene. In contrast, precore stop codon mutants were not detected, and variations of the HBV core gene were minimal in patients with acute hepatitis B. The association of HBV precore mutants and HBV core gene variations with fulminant hepatitis B and not acute hepatitis B suggested that these variations may be important in modulating the clinical course of HBV infection. PMID- 8200262 TI - Postprandial vascular response in patients with cirrhosis. Short-term effects of propranolol administration. AB - Systemic and portal hemodynamic parameters were evaluated in eight cirrhotic patients in basal conditions and after food intake and placebo. Following seven days of oral propranolol administration, hemodynamic parameters were reevaluated in the fasting and postprandial states under similar conditions. Cardiac output and portal blood flow were measured by Doppler technique. Intraobserver variability of repeated measurements was less than 10%. Food intake caused a significant increase of portal blood flow (+28%, P < 0.05). No significant changes were observed in the other hemodynamic parameters studied. Propranolol at doses achieving effective beta blockade (84 +/- 14 mg/day) (mean +/- SD) reduced portal blood flow (-24%, P < 0.05). Food intake caused a significant increase in portal blood flow (+35%, P < 0.05) in propranolol treated patients. However, in absolute values, postprandial portal blood flow during propranolol treatment was significantly lower (986 +/- 402 ml/min) than that obtained after the initial food intake (1214 +/- 537 ml/min, P < 0.05). Placebo administration had no significant hemodynamic effects in either group. This study demonstrates that chronic propranolol administration could protect from portal hemodynamic changes following food intake. Doppler technique is a reliable technique to evaluate changes on portal and systemic hemodynamic parameters during a short period of time in patients with cirrhosis. PMID- 8200263 TI - Biliary motility. Changes in detailed characteristics correlated to duodenal migrating motor complex and effects of morphine and motilin in dogs. AB - The temporal relationship of biliary motility to the duodenal migrating motor complex and effects of morphine and motilin were studied in five dogs prepared with a duodenal cannula. Common bile duct, sphincter of Oddi, and duodenal manometry were performed awake. Sphincter of Oddi phasic contractions occurred even during the quiescent period of duodenal phase I and its activity increased from phase II to III. Minimum basal pressure of sphincter of Oddi and common bile duct pressure decreased from phase I to phase III. Both morphine and motilin induced premature phase III in the sphincter of Oddi and duodenum. Latencies of the effect were 0.2 min for morphine and 3.2 min for motilin (P < 0.01). After morphine, vigorous continuous contractions with high basal pressure occurred, being interrupted by brief and repeated inactive periods, similar to spontaneous phase III. Motilin-induced phase III appeared indistinguishable from spontaneous phase III. Although both agents induced phase III in the sphincter of Oddi, differences in the latency and contraction pattern suggest different mechanisms of action of these agents on the sphincter of Oddi. PMID- 8200264 TI - Manual and automatic gallstone dissolution with methyl tert-butyl ether. AB - The aim of the study was to establish the efficiency of cholesterol gallstone dissolution with methyl tert-butyl ether in a large group of patients and to compare the results of patients treated manually by a nurse or using an automatic pump. Gallbladder puncture was successful in 228 patients (99%). After 9 hr, 211 patients (91%) were stone-free; 144 (68%) of them left the hospital on the fourth day. In radiolucent stones not isodense with bile on a CT scan, dissolution rate decreased by 10%, treatment time was prolonged by 40%. Forty-two of the 228 patients were selected for the hand-syringed group, 42 patients, who matched these patients in stone size and number, were treated with an automatic pump (Baxter). Stone burden in matched pairs was comparable. Stones dissolved in 96% of the patients in both groups. Sludge remained in the gallbladder in 52% after manual treatment and 60% after automatic therapy. Side effects were identical in both groups. None of the side effects were pump-related. Automatic therapy reduced the time needed by the nurse to treat each patient by 70%. PMID- 8200265 TI - Effect of single dose of oral erythromycin on gastric and gallbladder emptying. Simultaneous assessment by ultrasound. AB - To evaluate the effects of a single oral dose of erythromycin on gastric and gallbladder emptying, 10 volunteers, without a known history of gastrointestinal disease, were investigated. Erythromycin stearate (500 mg) or placebo was given on separate mornings 30 min before a standard solid meal in a randomized, double blind, crossover study. Gastric and gallbladder emptying rates were simultaneously evaluated by means of real-time ultrasonography. Gastric antral area and gallbladder volume were determined before the meal and 30, 60, 120, 180, 240, and 300 min after commencing eating. Erythromycin, compared to placebo, significantly accelerates and increases the degree of both gastric and gallbladder emptying. As previously reported for intravenous and chronic oral assumption, also a single dose of oral erythromycin is able to accelerate gastric and gallbladder emptying in normal human subjects. PMID- 8200266 TI - Increased biliary protein precedes gallstone formation. AB - Although nucleation is critical to the pathogenesis of cholesterol gallstones, the factors responsible for this process are poorly defined. Numerous potential nucleating agents have been identified in the bile of humans and animals with cholelithiasis, including mucus, calcium, and bilirubin. Recent studies have shown that patients with cholesterol crystals and gallstones have increased biliary total protein, suggesting that protein may be a previously unrecognized nucleating factor. We tested the hypothesis that biliary total protein is increased prior to cholesterol gallstone formation. Prairie dogs were maintained on either control (N = 22) or 0.4% cholesterol-enriched chow (N = 18) for up to 18 weeks. Cholesterol-fed animals were classified as pregallstone (N = 12) or gallstone (N = 6) based on gross examination of the gallbladder bile. Both hepatic and gallbladder biles were then analyzed for lipid, bile acid, calcium, and protein content. Cholesterol feeding was associated with increased gallbladder concentrations of cholesterol, phospholipids, and calcium in the pregallstone and gallstone groups. Biliary total protein was significantly elevated in the pregallstone (5.8 +/- 0.4 mg/ml, P < 0.001) and gallstone animals (6.0 +/- 0.6 mg/ml, P < 0.001) as computed to controls (3.8 +/- 0.3 mg/ml). Regression analysis showed positive correlations between gallbladder bile total protein and the gallbladder bile cholesterol saturation index (CSI) (P < 0.001), as well as between gallbladder total protein and calcium (P < 0.001). Although the hepatic bile CSI was elevated in cholesterol-fed animals, total protein remained unchanged, suggesting that the alteration in biliary protein is a gallbladder phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200267 TI - Effects of a new benzodiazepine derivative cholecystokinin receptor antagonist FK480 on pancreatic exocrine secretion in anesthetized rats. AB - Inhibitory effects of a newly developed benzodiazepine derivative (S)-N-[1-(2 fluorophenyl)-3,4,6,7-tetrahydro-4-oxo-pyrrolo-[3,2,1- jk][1,4] benzodiazepine 3yl]-1H-indole-2-carboxamide (FK480), a cholecystokinin (CCK) -A receptor antagonist, on pancreatic exocrine secretion were examined in vivo in anesthetized rats. The antagonism produced by FK480 was competitive in nature because intraduodenal as well as intravenous infusion of FK480 (50-250 nmol/kg/hr) caused a parallel rightward shift of the entire dose-response curve for cerulein-stimulated pancreatic exocrine secretion without altering the maximal increase. The magnitude of the shift was proportional to the dose of FK480. The mean pA2 and ID50 values of intravenously administered FK480 were 8.2 and 24 nmol/kg/hr, respectively, and those of intraduodenally infused FK480 were 7.7 and 168 nmol/kg/hr, respectively. Thus, FK480 given by the intravenous route was about sevenfold more potent than that given by the oral route. The antagonistic effects produced by intravenous FK480 were specific for CCK receptor in that the stimulatory effects of cerulein were inhibited whereas those of bombesin and secretin were not altered. In addition, intravenous administration of 50 nmol/kg/hr FK480 completely suppressed pancreatic exocrine secretion in response to intraduodenal infusion of 10% casein (400 mg/hr). FK480 was active as a CCK receptor antagonist for more than 12 hr because oral administration of FK480 (1.0 mg/kg) had significant inhibitory effects even after 12 hr on cerulein stimulated pancreatic exocrine secretion. These results indicate that FK480 is a potent, competitive, and specific CCK receptor antagonist on the exocrine pancreas in vivo, having oral bioavailability and a long biological half-life. PMID- 8200268 TI - Pancreatic lesions and modifications of pancreatic juice in tropical chronic pancreatitis (tropical calcific diabetes). AB - Seventeen Indian patients from Kerala State and 13 Indian controls were submitted to a dietary inquiry. Indian patients and controls had a low fat intake (40.8 g +/- 12.1 and 34.5 g +/- 11.0 per day, respectively) and a moderately low protein intake (52.8 +/- 9.5 and 47.8 +/- 11.3 g per day); 11 patients and 6 controls did not consume cassava. Pure nonactivated pancreatic juice was collected at endoscopy in 10 Indian patients who presented with tropical calcific diabetes, 12 apparently normal controls from the same area, and 23 apparently normal French controls. The only significant differences between Indian and French controls was a decreased pancreatic protein response to cerulein and an increased calcium concentration in the Indian subjects. The pancreatic juice of Indian patients was characterized by decreased volume, normal bicarbonate concentration, increased protein concentration when the acinar cells were not stimulated, with no response to cerulein, increased calcium concentration, and normal citrate concentration. These changes are very similar to the changes observed in French patients with chronic alcoholic pancreatitis. The lesions of 14 surgical resection pancreatic specimens from South Indian patients presenting with tropical pancreatitis were compared to pancreata from French patients presenting with chronic alcoholic pancreatitis. The only difference was that intraductal plugs, lesions of the duct epithelium, and retention cysts or pseudocysts were less frequent in Indians. These results show that the two nutritional forms of pancreatic lithiasis, alcoholic and tropical, have similar histological lesions and biochemical modifications of pancreatic juice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200269 TI - Trypsin(ogen) content of pancreatic calculi in chronic calcified pancreatitis in man. AB - Protein analysis of intraductal precipitates and calculi is important to elucidate the mechanism of stone formation in chronic pancreatitis. We revealed human cationic trypsin immunoreactivity in protein extracts of pancreatic stones from 11 of 13 patients with chronic calcified pancreatitis, ranging from 0 to 42.3 ng/micrograms protein. On gel filtration the immunoreactivity eluted as one peak, which is identical to that of human cationic trypsinogen. On immunostaining of pancreatic stone, using an immunogold technic and scanning electron microscopy, the immunoreactivity was observed more densely in the amorphous portion of the center of the stones than in the concentric laminar layer of the periphery. Only negligible activity was detected for elastase 1 or amylase in the stone extracts. These results suggest that the presence of trypsinogen in pancreatic stone is not due to coprecipitation or adsorption of pancreatic enzymes but that trypsinogen is more likely involved in an initial step of intraductal precipitate formation than in a subsequent step of stone formation. However, the absence of trypsinogen in the stones from two of the 13 patients also suggests that trypsinogen is not the sole protein initiating precipitate formation. PMID- 8200270 TI - Acute liver failure due to lymphoma. A diagnostic concern when considering liver transplantation. AB - Lymphomatous involvement of the liver may present as acute liver failure but is an absolute contraindication for liver transplantation. Therefore it is imperative to diagnose such patients since survival in this group is poor and recurrence is high. We describe two patients with acute liver failure referred for liver transplantation whose diagnostic testing revealed hepatic lymphoma. These cases underscore the importance of considering lymphoma in the differential diagnosis of acute liver failure prior to liver transplant. PMID- 8200271 TI - Gastrointestinal hemorrhage and intestinal ischemia associated with anticardiolipin antibodies. AB - Two patients developed unusual causes of severe gastrointestinal hemorrhage associated with anticardiolipin antibodies. One patient bled from small bowel ischemia and mesenteric thrombosis. Another patient bled massively from an ulcer of the descending duodenum which was refractory to standard antiulcer therapy. Ischemia may have contributed to the atypical ulcer presentation in this second patient, which included atypical ulcer location, ulcer refractoriness to standard peptic ulcer therapy, and severe recurrent hemorrhage. In five previously reported cases intestinal infarction associated with anticardiolipin antibodies presented, as it usually presents in patients without anticardiolipin antibodies, as an acute abdomen without acute gastrointestinal bleeding. The current study demonstrates that intestinal ischemia due to thrombosis is in the differential diagnosis of gastrointestinal bleeding in the anticardiolipin antibody syndrome. PMID- 8200272 TI - Duodenal diaphragmlike stricture induced by acetylsalicylic acid. AB - Many reports have mentioned the role of nonsteroidal antiinflammatory drugs in inducing diaphragm-like strictures in the small and large bowel. These lesions are mostly seen in patients with chronic use of nonsteroidal antiinflammatory drugs. We report the case of a 57-year-old man who developed a diaphragmlike stricture in the second part of the duodenum. The patient had been using a preparation containing acetylsalicylic acid during many years. Although a congenital origin of the diaphragm is not completely excluded, we postulate that this stricture probably occurred as a result of acetylsalicylic acid-induced ulcerations, followed by submucosal fibrosis. PMID- 8200273 TI - Toxocara canis infection presenting as eosinophilic ascites and gastroenteritis. AB - Eosinophilic ascites is rarely observed in clinical practice. It may be associated with the serosal type of eosinophilic gastroenteritis, abdominal lymphoma, hypereosinophilic syndrome, or peritoneal dialysis but is uncommonly related to parasitic infections. We report a case of a previously healthy young patient who developed diarrhea and exudative eosinophilic ascites. The final diagnosis was consistent with a parasitic infection due to Toxocara canis, while the clinical and radiological findings suggested an eosinophilic gastroenteritis. The diagnostic approach, especially parasitic serological data, which must be carefully interpreted, are discussed; in addition, the possible pathophysiological mechanisms involved in the production of ascites are evoked. PMID- 8200274 TI - [Quantitative analysis of six lectin receptors and its application in differential diagnosis of astrogliomas and reactive hyperplasia of gliocytes]. AB - The distribution of six lectin receptors (WGA, RCA-1, LCA, PSA, PNA, SBA) in 71 human astrogliomas, 8 human normal brain tissues and 11 reactive hyperplasia of gliocytes was examined by avidin-biotin-peroxidase technique and quantified with an image analysis. The results showed that WGA and RCA-1 may be used as good markers for distinguishing well differentiated astrocytomas from reactive hyperplasia of gliocytes. The quantities of LCA and PSA receptors of astrocytomas with different degree of differentiation were different. Expression of SBA and PNA receptors in normal brain tissues and different lesions was similar. The results suggest that glycoproteins and glycolipids with N-glucosidic bonds mainly changed in the process of histogenesis and differentiation of astrocytomas. PMID- 8200275 TI - [Multiple gene alterations in human esophageal squamous cell carcinoma]. AB - In 45 human esophageal squamous cell carcinomas, 29 showed alterations of EGFr, c myc, int-2, Rb and p53 gene by Southern blot hybridization, a frequency of 15.6%, 31.1%, 35.6%, 22.2%, 6.7%, respectively. Among these cases, 16 cases showed two or multiple gene changes, and most of them were of II-III stage. The results suggest that gene alterations may be related to pathological stages of the disease. The poorer the differentiation of the tumor, the more gene changes were accumulated. We did not find association between the presence of metastasis in lymph nodes and the gene alterations. PMID- 8200276 TI - [Mutation and expression of Rb gene in human esophageal cancer]. AB - The mutation and expression of Rb gene in human esophageal cancer (EC) were investigated by PCR-direct sequencing and Northern blot hybridization. In PCR amplification analysis, in one of 20 (5%) cases of EC was found to have Rb gene deletion in exon 17 and 21; in one of 6 cases of the adjacent non-tumours tissue was found to have deletion in exon 21. Esophageal carcinoma of human fetus induced by NMBzA had Rb gene deletion in exon 17 and 21 too. In PCR-direct sequencing analysis, four of 10 (40%) EC were found to contain Rb gene mutations in exon 17 and 21. In northern blot analysis, seven of 12 (58.3%) EC exhibited abnormal Rb gene expression, including inactivation in 6 abbreviated expression in one. The results suggest that Rb tumor suppressor gene might play an important role in carcinogenesis of EC. The mechanisms of Rb gene mutation, deletion or abnormal expression related to carcinogenic nitrosamine in the environment need further study. PMID- 8200277 TI - [Establishment and mechanistic characterization of SV40 T antigen immortalized human fetal hepatocytes]. AB - Human fetal liver cells were cultured in serum free media enriched with hydrocortisone and infected with retrovirus containing SV40 large T gene. Replicating colonies with G-418 resistance developed in 50 days through 23 passages, while none grew in control dishes. After a crisis of 3 months duration, three colonies resumed active proliferation for over 15 months through 60 passages and became immortalized. These cells had epithelioid morphology, and were stained positively for CK-18. Southern blot and immunocytochemistry demonstrated the presence and expression of SV40 T-antigen in the immortalized cell lines. The cells expressed human albumin, especially in those while in cycle. Accumulation of p53 protein in the cell nuclei and strong expression of TGF-alpha as shown by immunocytochemistry explained at least partly the mechanism of unlimited growth of these immortalized human hepatocytes. These cells did not show anchorage-dependent growth in soft agar, nor did tumor form when inoculated into nude mice. These immortalized, differentiated, non-malignant human fetal hepatocyte lines may be useful for further studies. PMID- 8200278 TI - [Specific cytotoxicity of recombinant interleukin 6-pseudomonas exotoxin fusion protein (IL6-PE40) on LT12 leukemic cells expressing high levels of interleukin 6 receptor (IL6R)]. AB - An acute promyelocytic leukemic cell line LT12 was transduced with IL6R cDNA by electroporation. The resultant LT12-IL6R+ leukemic cells expressed more than 1000 IL6R per cell. The effect of the recombinant IL6-PE40 on both the LT12-IL6R+ cells and the IL6R- parental cells (LT12-IL6R-) was studied by leukemic progenitor colony (CFU-L) formation and 3H-TdR incorporation assays. It was found that IL6-PE40 at concentrations ranging from 1 to 1,000 ng/ml inhibited CFU-L formation and DNA synthesis of LT12-IL6R+ cells in a dose-dependent manner. No inhibition was seen at the same concentration range in LT12-IL6R- cells. At concentrations of 250-1000ng/ml, IL6-PE40 led to only 40% inhibition of DNA synthesis in LT12-IL6R- cells. Inasmuch as rIL6 at the same concentrations had no significant effect on both IL6R+ and IL6R- cells, we concluded it is IL6-PE40 that exerts its highly specific killing on leukemic cells expressing high levels of IL6R. PMID- 8200279 TI - [Modulation of mutagenic drug-induced unscheduled DNA synthesis (UDS) in primary rat hepatocytes by diallyl trisulfide]. AB - Most anticancer drugs are mutagenic/carcinogenic. A possible exception is diallyl trisulfide (DAT), a component of garlic, which inhibits growth of transplantable tumors in vitro and in vivo and mutagenicity and carcinogenicity of genotoxic agents. It is an antimutagenic anticancer chemical. Its modulating effect on induction of UDS by mutagenic mitomycin C (MMC), cyclophosphamide (CP), and cis diamine dichloroplatin (DDP) was investigated with the assay in primary cultures of Wistar rat hepatocytes by autoradiographic technique. Results showed that MMC (1-10 mumol/L), CP (0.316-3.16mmol/L), and DDP(3.16-31.6mumol/L) resulted in a significant induction of dose-dependent UDS and that DAT (0.5-4.0 mumol/L) significantly enhanced induction of UDS by MMC, CP and DDP while DAT itself did not. A dose-response relation was also observed between the dosage of DAT and the enhancement of induction of UDS. Hepatocellular enzymes for metabolic activation of indirect mutagens may not be involved in the enhancement of UDS-induction since DAT also increased UDS level induced by direct mutagen DDP. DAT promotes UDS induction probably by increasing repair of damaged 4-DNA. DAT, an anti infection antibiotic, may be used in cancer chemotherapy to alleviate the adverse side effects of chemotherapeutic agents with mutagenic/carcinogenic activities. PMID- 8200280 TI - [Evaluation of detecting 9 tumor markers in serum for diagnosis of primary liver cancer]. AB - Nine tumor markers in serum including alpha-fetoprotein (AFP), r glutamyltranspeptidase (GGT), lactate dehydrogenase (LDH), alpha 1-antitrypsin (alpha 1-AT), total sialic acid (TSA), ferritin (Ft), ceruloplasmin (CP), LDH isoenzymes and GGT isoenzymes were used for differential diagnosis of primary liver cancer. Of 5 measurement data tested by statistics, CP and TSA were close to normal distribution (P > 0.1), GGT, LDH and alpha 1-AT showed skewness distribution or to be close to normal distribution with in transformation (P > 0.1). The results indicated that the determination of the cut-off value should depend on the statistical distribution of data. Analysis of single and dual combination tests as well as triple analysis with sequential progressive screening had been performed to evaluate the predictive value of clinical diagnosis, i.e. the sensitivity, the specificity and the correct diagnosis efficiency. Three predictive values of a single test were lower than what clinical diagnosis raqvest. The dual-combination tests had higher specificity but a lower sensitivity. For triple analysis with sequential progressive screening among the liver cancer group (n = 23), the related disease group (n = 44) and the healthy individuals group (n = 40), the correct diagnosis efficiency was 95%, 97.3% and 100%, respectively. This suggests that the method described here has potential value in clinical practice. PMID- 8200281 TI - [Effect of hepatocellular carcinoma-specific transfer factor (HCC-S-TF) on IL-2 activity and IL-2R expression]. AB - HCC specific transfer factor (S-TF) was extracted from lymphoid tissues of goats immunized with HCC cell suspension. The effect of the S-TF on IL-2 activity and IL-2R expression was observed in vitro. The results showed that IL-2 activity and IL-2R expression in HCC patients but not in normal subjects could be increased by the S-TF. The IL-2 activities and IL-2R expressions in both normal subjects and patients with HCC could not be increased by normal transfer factor (N-TF). This may be one of the anti-tumor mechanisms of S-TF. It suggests that S-TF may be better than N-TF in immunotherapy of human tumors. PMID- 8200282 TI - [Chemosensitivity testing of fresh human gastrointestinal cancers using AgNOR assay]. AB - The argyrophilic staining of nucleolar onganizer region (AgNOR), a simple colorimetric test, has been adapted for chemosensitivity testing of human gastric and colorectal cancers. Seven different chemotherapeutic agents were tested. The drug sensitivity was measured and compared according to the decrease rate of AgNOR granules between control tumor cells and tumor cells treated with antitumor drugs. Only 3 of 10 cases of advanced gastric carcinoma were sensitive to one antitumor agent. Most colorectal carcinoma cases (18/20) were sensitive to at least one antitumor agent. The sensitive sequence of antitumor agents we have had in this study was relative to clinic. The method and characteristics of AgNOR assay as a chemosensitivity test was introduced. It's value is being observed. PMID- 8200283 TI - [MRI staging of endometrial carcinoma]. AB - Thirty-one patients clinically suspected for endometrial carcinomas were evaluated by MRI. MR imaging findings were compared with surgico-pathologic staging of the tumor following hysterectomy. The MR appearance of endometrial carcinoma included uterine enlargement, endometrial thickness greater than 1 cm, and nodular-massive pattern which was observed mainly on T2-weighted imaging. The tumor on T2-weighted image was of high homogeneous signal intensity and was indistinguishable from surrounding endometrium. When the junctional zone of endometrium-myometrium, so-called low signal zone, depicts segmental interruption or disappearance, it indicated that the tumor had invaded into the myometrium. If cervical canal was widened, with heterogeneous distribution of high signal intensity, cervical involvement by the tumor was demonstrated. According to criteria of MR staging of endometrial carcinoma proposed by Hricak, the accuracy of our results of MR staging was 87%. Therefore, we suggest that preoperative MR examination is useful for staging of endometrial carcinoma. PMID- 8200284 TI - [Primary leiomyosarcoma of the inferior vena cava--a report of 4 cases]. AB - Primary leiomyosarcoma of the inferior vena cava (IVC) is of rare occurrence. From 1988 to 1992, 4 cases, all female, were treated in our hospital. Symptoms of this rare tumor were not typical except pain in the abdomen and the back. But it was painless in one patient. Diagnosis was solely dependent on imaging with regard to tumor localization, size and extent of invasion to adjacent organs. The best treatment of choice was excision of the tumor with the IVC affected. Tumor located in the middle and lower third of IVC usually involving the right renal vein. Therefore, it was necessary to remove the right kidney, when provided the left kidney was functionally normal. One patient died postoperatively of pulmonary embolism and the other died of hepatic failure due to multiple metastases in the liver. PMID- 8200285 TI - [Synchronous and metachronous bilateral testicular germ cell tumors]. AB - Eleven of 605 (1.82%) patients evaluated at this Cancer Hospital for testicular germ cell malignancy between 1958 and 1992 had evidence of bilateral testicular malignancy. The age ranged from 28 to 72 years. Five patients had a history of undescended testes and one of them was surgically corrected at age of 11 years. Four of these were synchronous and seven metachronous. Histologically, all four synchronous tumors were pure seminoma. Two of seven metachronous tumor cases had unilateral testicular non-seminoma. The other 5 patients had pure seminoma. The second tumor was diagnosed between 8 months to 150 months after diagnosis of the first one. Three of 7 (42.9%) patients were diagnosed within 5 years. Two patients with synchronous tumors died within 1 year (3 months and 6 months, respectively). Only one patient with metachronous tumors died of the disease. This study indicates that the overall prognosis and outcome depends on the histologic type and stage of the disease and reemphasizes the low but definite risk for development of a second testicular malignancy. PMID- 8200286 TI - [Growth and spread patterns of early gastric cancers]. AB - The growth pattern, status of infiltration in the mucosa, the depth of infiltration of cancer cells and the major changes of gastric mucosa in 100 cases of early gastric cancer (EGC) were studied retrospectively. According to histopathological examination, the growth pattern and spread of EGC can be described as follows: (1) In-situ malignant change in glandular tubules; (2) Expanding growth; (3) Diffuse infiltration; (4) Cancer cell nest growth; (5) Addition growth of cancer focus; (6) Multicentric carcinogenesis. The authors found that the growth and spread patterns were diverse, since in many cases there were two or more histological types in the same tumor. Even a single cancer focus of a particular histological type may display different patterns of infiltration in different directions. The authors also compared and discussed the features of EGC differing from those of advanced gastric cancers. PMID- 8200287 TI - [Significance of platelet aggregation in patients with malignant tumor of the head and neck]. AB - Platelet aggregation test (PAgT) was done in 492 patients with malignant tumor of the head and neck, and in 100 healthy adults and 33 patients with benign tumors of the head and neck. The results showed: (1) The maximum aggregation rate (MAR) of the pretreatment group, recurring group and distant metastasis group of the malignant tumor patients were significantly higher than that of healthy adults, benign tumor and posttreatment group of malignant tumor patients; (2) There was no significant difference between MAR of healthy adults and the patients with benign tumor of the head and neck; (3) MAR was enhanced as the tumor progress. The Results indicate that (1) Platelet aggregation in malignant tumor of the head and neck is enhanced; and (2) PAgT might be used as a reference index for the nature, development, effect of treatment and prognosis of tumors. The mechanisms of enhancement of platelet aggregation in malignant tumor, and the role of platelet in pathogenesis of proliferation and metastasis of tumors were also discussed. The clinical use of the platelet-inhibitory agents for anti proliferation and metastasis of tumors was in prospect. PMID- 8200288 TI - [Lung cancer with extra pulmonary symptoms as the chief manifestation. A clinical analysis of 47 cases]. AB - In patients with cancer of the lung, extrapulmonary symptoms can be found before or after the tumor is discovered. In this paper, 47 cases of lung cancer presenting extrapulmonary symptoms as their major clinical manifestation are reported. The symptoms might arise from the central nervous system, bones and joints, esophagus, intestine, etc. Some of the symptoms were due to compression or invasion of the cancer to the adjacent organs. Paraneoplastic syndromes, such as ectopic endocrine syndrome and carcinoid syndrome, were also encountered. Keeping these extrapulmonary manifestations in mind, patients suspicious of having lung cancer should be carefully examined and closely followed up until a correct diagnosis is made. PMID- 8200289 TI - [Bronchiectasis with concomitant lung cancer--a report of 7 cases]. AB - This article reports 7 cases of bronchiectasis with concomitant lung cancer, accounted for 3.6% of 194 cases of bronchiectasis admitted in the same period. The carcinoma originated from the pulmonary tissue with bronchiectasis in 5 cases, and from the superior segment of lower lobe with bronchiectasis in the basal segment in the other two cases. In 5 cases (71.4%) the tumor was smaller than 3 cm in diameter or only invaded into the submucosa, representing an early stage cancer. On the plain films of the chest only one case revealed a mass suspecting of the presence of carcinoma. Obviously it was hard to make a correct diagnosis in such a situation. In our group, correct preoperative diagnosis was made only in two cases and suspected of concomitant cancer in 3, while in the other two cases a definite diagnosis was obtained postoperatively by histopathological examination. In one of those two cases the lesion was so small that the diagnosis was made after several consecutive pathological examinations. It is emphasized that cytological examination of sputum and bronchoscopy should be performed in every patient. A CT scanning of the chest is of great help to find very small foci. Any massive lesions revealed on the film or CT scanning should be considered as a lung cancer. During operation pulmonary nodules should be also considered as possible cancers. The surgical specimen should be examined thoroughly to avoid missing of any minute cancer foci. PMID- 8200290 TI - [Panmyelosis--a report of 4 cases]. AB - From January 1987 to December 1990, 4 cases of panmyelosis were diagnosed in our hospital, which accounted for 1.36% of all acute nonlymphocytic leukemia cases. The clinical manifestation was similar to that of acute leukemia Hb ranged from 38 to 60 g/L, WBC 5.6 x 10(9)-14.0 x 10(9)/L, blasts in peripheral blood 1%-47%. Erythroblasts and megakaryocytes were also seen in peripheral blood. Platelets were 13 x 10(9)-240 x 10(9)/L. The myelogram showed hypercellularity. Myeloblast type I+type II accounted for 26.1%-51.6% of non-erythrocytic cells. Auer body could be seen in three cases and there was a leukemic gap in each. Erythrocytic series was 34.5%-84.5% with abnormal erythroblasts. PAS staining was positive in 60%-100% erythroblasts. Megakaryocytes were 545- > 1,000/1.5 cm x 3 cm and megakaryoblasts plus promegakaryocytes were 32%-43%. There were micro megakaryoblasts like lymphocyte in size in marrow smear and PAS staining for megakaryocytes was strongly positive. The diagnostic criteria, differential diagnosis and treatment for the disease were discussed. PMID- 8200291 TI - Insulin-receptor kinase is enhanced in placentas from non-insulin-dependent diabetic women with large-for-gestational-age babies. AB - The function of insulin receptor and IGF-1 receptor was investigated in placentas from 10 healthy control mothers, 8 diabetic mothers with appropriate-for gestational-age babies (AGA group) and 9 diabetic mothers with large-for gestational-age babies (LGA group). None of the diabetic mothers were obese before pregnancy; their blood glucose was well controlled during pregnancy and glycosylated HbA1c was 6.52 +/- 0.71% (M +/- S.E.). Insulin and IGF-1 receptors were partially purified from placentas using wheat germ agglutinin chromatography. The insulin-binding capacity was significantly increased in both the AGA and the LGA groups compared to the control, whereas the IGF-1 binding capacity was similar in the three groups. Autophosphorylation studies were performed with partially purified receptors equalized for similar binding capacity, then immunoprecipitated with anti-insulin receptor antibody or anti-IGF 1 receptor antibody. Insulin-stimulated 32P-incorporation into the insulin receptor beta-subunit was increased by 133% in the LGA group versus the control, whereas incorporation in the AGA group was equivalent to the control. Insulin stimulated tyrosine kinase activity of the receptor preparation for histone H2B phosphorylation was also significantly increased in the LGA group compared to the control. 32P-incorporation into beta-subunit IGF-1 receptor and IGF-1-stimulated tyrosine kinase activity did not show any significant differences among the three groups. The data in the present study suggest that elevated insulin receptor kinase might be involved in fetal overgrowth in diabetic mothers. PMID- 8200292 TI - The role of insulin in coronary atherosclerosis. AB - In 197 patients with coronary artery disease (CAD) who underwent coronary angiography, 75 g oral glucose tolerance test (OGTT) was performed, measuring plasma glucose(PG) and plasma insulin (IRI) at 4 time points (0, 30, 60 and 120 min). Subjects were separated into two groups by their insulinogenic index (I.I. = delta IRI/delta PG from 0 up to 30 min), 99 cases with good insulin response (I.I. > or = 0.4) and 98 cases with poor insulin response (I.I. < 0.4). Only two subjects were diabetic in good insulin response, while 37 were diabetic in poor insulin response. The severity of coronary atherosclerosis was expressed as a coronary index (CI), calculated according to Balcon's method. Fasting PG and the sum of PG were significantly higher in the latter group, while the sum of IRI was significantly lower. CI was not significantly different, however. In the group with good insulin response, the severity of CAD was significantly correlated to fasting IRI (n = 99, r = -0.387, P < 0.02), but, there was no such relationship in the other group. We conclude that hyperinsulinemia might be a risk factor for ischemic heart disease, but in diabetics it is difficult to link the relationship between fasting IRI and CI. PMID- 8200293 TI - Plasma t-PA and PAI-1 antigen concentrations in non-insulin dependent diabetic patients: implication for diabetic retinopathy. AB - Parameters of fibrinolysis, including basal plasma tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) antigen levels were studied in 49 non-insulin dependent diabetic patients (23 men, 26 women: ages 51.3 +/- 14.9 years) and 16 age matched non-diabetic subjects (9 men, 7 women ages 49.8 +/- 12.2 years) as a control group. Compared to a control group, the diabetic patients had a significantly higher mean plasma t-PA antigen (4.94 +/- 2.68 vs 3.20 +/- 2.30 ng/ml) and PAI-1 antigen (34.86 +/- 16.71 vs. 17.60 +/- 15.36 ng/ml) levels (P < 0.05). Significant univariate correlations were observed between t-PA and body mass index (BMI) (P = 0.0009, r = 0.7217), and PAI-1 were positively correlated with BMI and FBS (fasting blood sugar) in the total diabetic patients (P = 0.0003, r = 0.7217; P = 0.0477, r = 0.2858, respectively). In diabetic patients with proliferative diabetic retinopathy, both PAI-1 and t-PA antigen levels were significantly lower than those of diabetic patients with negative or background retinopathy (P = < 0.05). There were no significant differences of the plasma t-PA and PAI-1 levels between diabetic patients with micro- and macroproteinuria. This study conducted on non-insulin dependent diabetic patients suggests that they have significantly higher t-PA and PAI-1 antigen levels than do control subjects, and these findings appear to correlate negatively with proliferative retinopathy observed among the patients studied. PMID- 8200294 TI - Spontaneous remission of diabetes arrests progression of nephropathy in streptozotocin-treated spontaneously hypertensive rats. AB - Although antihypertensive therapy retards the progression of diabetic nephropathy associated with hypertension, it is not known whether glycemic control reverses or arrests diabetic nephropathy under untreated hypertension. We previously reported that spontaneous remission of diabetes occurred in the neonatal streptozotocin (STZ) model of spontaneously hypertensive rats (SHR) after 28 weeks of age, whereas hypertension persisted. Thus, we studied diabetic nephropathy before and after the recovery from hyperglycemia in this model. Two day-old male SHR were injected intraperitoneally with STZ or vehicle for control. Hypertension was developed and maintained in both STZ and control groups in a similar degree. Before the amelioration of hyperglycemia, urinary albumin excretion increased progressively in STZ-treated SHR as compared with control (24 weeks; 1.6 +/- 0.5 mg/day, 17.5 +/- 2.3 mg/day, P < 0.001), and renal and glomerular hypertrophies were seen with mesangial expansion in STZ-treated SHR. However, along the recovery from hyperglycemia, urinary albumin excretion did not increase in the STZ-treated group, while it consistently increased in the control group (52 weeks; 25.4 +/- 10.0 mg/day, 29.7 +/- 11.4 mg/day, not significant). Furthermore, there were no significant differences in renal weight, glomerular tuft area, and the incidence of glomerular sclerosis between the two groups at 52 weeks of age. This study suggests that glycemic control may be effective for diabetic nephropathy even in the coexistence of untreated hypertension. PMID- 8200295 TI - Exaggerated epinephrine response to hypoglycemia in a physically fit, well controlled IDDM subject. AB - Metabolically well controlled insulin-dependent diabetic subjects (IDDM) have deficient autonomic adrenomedullary responses to hypoglycemia. This defect, coupled with the characteristic deficient glucagon response to hypoglycemia, predisposes well-controlled IDDM subjects to an increased incidence of severe hypoglycemic episodes. In this report we describe a physically trained subject with long-duration IDDM (9 years) who was rigorously well-controlled (normal HBA1c), yet had exaggerated epinephrine responses to hypoglycemia compared with normal controls. Steady state epinephrine levels during a low-dose insulin (9 pM/kg/min) hypoglycemic clamp (2.9 +/- 0.1 mM) were approximately 2-fold higher compared with normal controls (10.6 vs. 5.5 +/- 0.7 nM). Epinephrine levels during a high-dose insulin (30 pM/kg/min) hypoglycemic clamp (2.8 +/- 0.1 mM) were also increased compared with normal controls (13.1 vs. 8.8 +/- 0.6 nM). We conclude that physical training in this metabolically well-controlled IDDM subject was associated with an augmented autonomic adrenomedullary response to hypoglycemia. PMID- 8200296 TI - Thyroglobulin antibodies in type 1 diabetic patients and their relatives- measurement with highly sensitive assay. AB - Autoimmunity in Type 1 (insulin-dependent) diabetes mellitus was assessed by measuring thyroglobulin antibodies (TGA) using a highly sensitive enzyme immunoassay in 65 young patients with Type 1 diabetes mellitus, 83 healthy first degree relatives of the patients, 37 healthy control subjects and 67 healthy parents of the control subjects. TGA were found in 78.5% (51/65) of patients and were significantly more frequent in patients than in control subjects (40.5%, 15/37; P < 0.01). The prevalence of TGA in patients showed no correlation with age at onset, duration of diabetes or sex. Among the first-degree relatives the prevalence of TGA was significantly increased in mothers of patients than in mothers of the control subjects (80.0% vs. 54.3%, P < 0.05), while not significantly between fathers of patients and fathers of control subjects or between siblings of patients and control subjects. Comparing the TGA levels of TGA-positive subjects, the TGA levels in patients, their parents and their siblings were significantly higher than those in the corresponding control subjects (P < 0.05, P < 0.05 and P < 0.01, respectively). In the present study we thus more clearly demonstrated autoimmune diathesis in patients with Type 1 diabetes and in their first-degree relatives. PMID- 8200297 TI - Anaerobic threshold can provoke microalbuminuria in non-insulin-dependent diabetics. AB - We examined two groups of non-insulin-dependent diabetic men (group A, 13 patients without microalbuminuria; group B, 9 patients with intermittent microalbuminuria) to ascertain whether the anaerobic threshold (AT) can provoke microalbuminuria, comparing them with 12 healthy subjects matched for age and sex (group C). All subjects exercised on a bicycle ergometer until the AT was reached. In intermittent microalbuminuria, the albumin:creatinine ratio (ACR) was over 0.25 mg/mmol.Cr 1-3-fold in 5 measurements. The ACR after exercise was increased to over 0.25 mg/mmol.Cr in 4/9 cases in group B (P < 0.05), in 2/13 cases in group A, but not at all in group C. We also studied the mechanism of exercise-induced microalbuminuria. In group B, ACR before exercise correlated positively with the baseline plasma glucose. Furthermore, positive correlation was found between ACR after exercise and HbA1c in group B. The AT did not affect the urinary beta 2-microglobulin in any groups. The plasma atrial natriuretic factor (ANF) after exercise was elevated most prominently in group B (P < 0.05). Positive correlation was found between increments of ACR and increments of plasma ANF after exercise in group B. We conclude that the AT can provoke microalbuminuria in some non-insulin-dependent diabetics. The plasma ANF and metabolic control may play an important role in the pathophysiology of exercise induced microalbuminuria. PMID- 8200298 TI - Delayed onset of diabetes in children of low economic stratum--a study from southern India. AB - Influence of the socioeconomic status on the age at onset of insulin-dependent diabetes mellitus (IDDM) was analysed in 614 patients who developed diabetes < or = 20 years. The peak occurrence was seen at 11 years in girls (n = 293). The boys (n = 321) showed multiple peaks between 11 and 18 years. In the urban patients (n = 463), the peak was at 11 years in contrast to a delayed peak at 18 years in the rural group (n = 151). When analysed with respect to the family income, the higher income group (HIG) (Rs > 2000/month) showed a sharp peak at 11 years whereas the lower income group (LIG) showed a peak at 18 years (chi 2 = 7.2, P = 0.007). The median body weight of the LIG was lower compared to the HIG. Although the exact cause for the delayed age at onset of IDDM in the rural or LIG is not known, it is likely to be a consequence of the lower socioeconomic and nutritional status (indicated by low body weight) and probably indicates the influence of environmental factors in the pathogenesis of the disease. PMID- 8200300 TI - Insulin autoimmune syndrome (Hirata disease): clinical features and epidemiology in Japan. AB - Since Hirata et al. first reported a patient with insulin autoimmune syndrome in 1970, 197 cases have been reported in Japan as of December, 1992. The clinical profiles of these 197 cases were as follows; the peak age at onset was 60-69 years and peak duration of hypoglycemic attacks was more than 1 and less than 3 months. There was no gender difference in the peak age of onset or duration of hypoglycemic attacks. Approximately 82% of the IAS patients had spontaneous remission without any positive treatment. Before diagnosis of IAS, 43% of the patients with IAS had been taking medication; methimazole (MTZ) for Graves' disease, alpha-mercaptopropionyl glycine (MPG) for cataracts, liver disease or rheumatoid arthritis, or glutathione for liver disease, all of which are sulfhydryl compounds. After such sulfhydryl compounds were discontinued, the hypoglycemic attacks subsided. Three patients with IAS experienced recurrence of the hypoglycemic attacks after re-administration of MTZ and MPG, although 6 patients who developed IAS without exposure to any drug had recurrent attacks without exposure to any drug around 1 year after the first hypoglycemic attacks had stopped. Thus, hypoglycemia in IAS is mainly transient and the development of IAS may be related to sulfhydryl compounds. PMID- 8200299 TI - Analysis of the contribution of the HLA system to the inheritance in the Wolfram syndrome. AB - The Wolfram syndrome (WS) is an autosomal recessive disorder beginning in childhood that consists of four clinical features: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. Its pathogenesis remains unknown, although the tendency to develop this syndrome has been related to some class II antigens of the HLA system. We report six new cases in four families. A review of published data from the genetic features of this syndrome is performed, establishing the high frequency of the HLA-DR2 antigen in the WS (44.4%) compared with a control group (21.9%; relative risk, 2.8) and to patients with Type 1 insulin-dependent diabetes mellitus (Type 1 diabetes) (6.77%; relative risk, 9.7). We also comment the high frequency of the HLA-DQw1 antigen (85.5%) in this syndrome, without statistical significance. A familial segregation study of the HLA haplotypes has been carried out without finding correlation between the autosomal recessive pattern attributed to the WS, and the major histocompatibility complex. In conclusion, whereas HLA may increase susceptibility to the WS, as shown by the existence of an HLA-DR2 association, the major genetic influence on the inheritance of the WS must be at another locus. PMID- 8200301 TI - Effect of the sulfonylurea glyburide on superoxide dismutase activity in alloxan induced diabetic rat hepatocytes. AB - In the present study we administrated glyburide (glibenclamide) to type 2 (NIDDM) diabetic rats and determined the effect of such treatment on liver superoxide dismutase (SOD) activity. Hepatic SOD activity was significantly reduced in diabetic animals. Glyburide treatment of diabetic rats for 4 weeks corrected the changes observed in diabetic liver. In addition, blood glucose levels of untreated diabetic rats decreased following glyburide treatment. Administration of glyburide to diabetic rats reversed the diabetes-induced changes, suggesting that glyburide may directly increase liver SOD enzyme activity. PMID- 8200302 TI - Islet amyloid polypeptide gene: no evidence of abnormal promoter region in thirty five type 2 diabetic patients. AB - Aberrant expression of the IAPP gene may be involved in the pathogenesis and islet amyloid formation of type 2 (non-insulin dependent) diabetes mellitus. We sequenced 536 basepairs in the 5'-upstream sequence of the gene of 35 Japanese with this disease and 3 patients with maturity-onset diabetes in the young. The sequences corresponding to both alleles of the gene were identical to one another and to the sequence of subjects without diabetes mellitus except for one allelic variation of 'A' and 'C' at the position -230. Analysis by allele specific polymerase chain reaction revealed no significant difference in frequency of the variation at this position between normal and type 2 diabetic subjects. We conclude that the 5' region of the IAPP gene is highly conserved and only 1 DNA polymorphism is detected and that this polymorphism does not associate with type 2 diabetes mellitus. PMID- 8200303 TI - [The relationship between insulin resistance, hyperinsulinemia and hypertension, coronary heart disease]. PMID- 8200304 TI - [A study on the mechanism of hyperinsulinemia in essential hypertension]. AB - Blood glucose(BG), insulin(IS), C-peptide(CP), glucagon(GC) and their area under the curve(AUC), the CP:IS molar ratio and IS:GC molar ratio were measured and calculated in 31 hypertensives and 23 weight control normotensives. Compared with the normotensives, the patients showed higher fasting serum IS, CP and the IS:GC ratio, and exhibited increased BG, IS, CP and their AUC and the IS:GC ratio, and a lower CP:IS molar ratio after the oral glucose load. No significant difference was found in the fasting CP:IS molar ratio, BG, GC between normotensive and hypertensive subjects. The results indicate that there are impaired glucose tolerance, hyperinsulinemia and IS resistance in essential hypertensive subjects. The hyperinsulinemia may be caused by a beta-cell hypersecretory response to the defective peripheral action of the hormone and by a decreased hepatic insulin clearance. The study also suggests that IS resistance in essential hypertensive subjects usually involve other abnormalities of metabolism and associate with increased risk factors for coronary artery disease. PMID- 8200305 TI - [A preliminary study of insulin resistance in essential hypertension, simple obesity and acromegaly]. AB - Plasma glucose and serum insulin during OGTT were measured in 33 patients with essential hypertension, 17 patients with simple obesity, 19 patients with acromegaly and 10 normal adults. Compared with control, serum insulin concentration increased in 33 patients with essential hypertension at 3 hour postload (P < 0.05) and in 17 patients with simple obesity at 1 hour postload (P < 0.05) during OGTT, 19 patients with acromegaly also had their insulin concentration increased at 1.3 hour postload (P < 0.05) during OGTT. The correlationships between diastolic blood pressure and integrated area under the curve for serum insulin concentration (r = 0.3838, P < 0.05) were observed in 33 patients with essential hypertension. Serum insulin concentration decreased in 10 patients with essential hypertension at 1 and 2 hour postload during OGTT after antihypertensive treatment with captopril or captopril plus hydrochlorothiazide. The results indicated that the patients with essential hypertension, simple obesity and acromegaly are insulin resistant and hyperinsulinemic after an oral glucose load. PMID- 8200306 TI - [Insulin resistance and its relationship to intracellular calcium metabolism in essential hypertension]. AB - Insulin resistance (IR) and intracellular calcium metabolism in 26 essential hypertensive (EH) patients (18 non-obese, 8 obese) were studied and compared with 24 normotensive (NT) subjects. The changes of plasma insulin and glucose before and after intravenous glucose tolerance test (IVGTT), the platelet cytoplasmic ionized calcium concentration ([Ca2+]i) with the fluorescent indicator Quin 2 and the Ca2+ pump activities in erythrocyte (RBC) lysates with the improved Vincenzi method were studied. These results strongly suggest that essential hypertension is characterized by fundamental metabolic abnormalities as well as hemodynamic abnormalities. Insulin resistance and abnormalities of cellular calcium metabolism, such as elevation in cytoplasmic [Ca2+], decrease in basal Ca-pump activity which rendered an increment of cytoplasmic [Ca2+], are major metabolic disturbances in patients with EH. The interaction between IR and cytoplasmic [Ca2+] is very complicated and needs further studies. PMID- 8200307 TI - [Association between insulin and blood pressure in relation to the influence of body mass index]. AB - The relationship between plasma insulin level and systolic blood pressure (SBP) was investigated by multiple linear regression procedure in 410 Chinese non diabetics. The significant positive correlation between SBP and 2-hour plasma insulin (INS 2h) after 75g glucose load was found in the BMI (body mass index) 15.9-27.0 group (n = 287) after the adjustment for age, sex, BMI, smoking and plasma cholesterol (P = 0.01). However, this significant correlation was gradually diminished with the expansion of the BMI range, ie. P = 0.04 in the BMI 15.9-29.0 (n = 356) group, P = 0.07 in the BMI 15.9-31 (n = 389) group, and P = 0.12 in the BMI 15.9-33 (n = 402) group after the same adjustment of variables. Interestingly, the significant inverse correlation between insulin-BMI interaction term (product of BMI and insulin) and SBP was found (P = 0.04) in the presence of the significant positive correlation between 2-hour plasma insulin and SBP (P = 0.02) after adjustment of the above mentioned five factors in the whole group (BMI 15.9-42.2, n = 410). These results indicated that SBP is independently correlated with plasma insulin level in the studied population, and that the severer obesity may interfere the net effects of insulin on the elevating of blood pressure. PMID- 8200308 TI - [The insulin secretion and pharmaceutical interference in hypertensive patients and their normotensive children]. PMID- 8200309 TI - [The relationship between increased QT dispersion of acute myocardial infarction and ventricular fibrillation]. AB - We measured 62 patients' QT dispersion (QTd) and JT dispersion (JTd) of acute myocardial infarction (AMT) on first ECG within 48 hour. The results showed that QTd and JTd were greater in 16 patients with ventricular fibrillation (Vf) compared without Vf (QTd mean 107.50 +/- 35.80ms to 48.90 +/- 17.90 ms, P < 0.01; JTd mean 107.50 +/- 31.00ms to 52.60 +/- 19.00 ms, P < 0.01) during the early phase of AMI. That long QTd and/or JTd may possibly relate to Vf of AMI. Thus, we suggest that QTd and/or JTd may be of significant prediction value for prognosis of AMI. PMID- 8200310 TI - [Measurement of the uprising peak rate of right ventricular pressure-A simultaneous Doppler echocardiographic and cardiac catheterization study]. AB - To develop a new method for measuring the right ventricular systolic function noninvasively, Doppler echocardiography (DE) and cardiac catheterization (CC) were simultaneously performed in 31 patients with tricuspid regurgitation (TR). The regurgitant velocities were recorded by the continuous-wave Doppler technique and converted into the instantaneous pressure gradients and right ventricular pressures using a modified Bernoulli equation. The uprising peak rate of the right ventricular pressure (IP) at the time point of dp/dt max and the ratio of dp/dt max/IP were calculated from both the pressure curves and Doppler spectra. The result showed that there were high correlations of dp/dt max, IP and dp/dt max/IP measured by DE and CC (r = 0.87, 0.89 and 0.89, respectively). The conclusion is that DE provides a feasible and reliable approach to the noninvasive estimation of the right ventricular systolic function in patients with TR. PMID- 8200311 TI - [Effects of rotundium on clinical electrophysiology in patients with pre excitation syndrome]. AB - Acute electrophysiologic effects of rotundium were studied with programmed electrical cardiac stimulation in 14 patients with paroxysmal tachyarrhythmias due to preexcitation syndrome after intravenous infusion of 2 mg/kg. The results showed that the drug depressed the function of the atrioventricular node markedly. Significant lengthening of A-H interval (from 75 +/- 19ms to 88 +/- 21ms, P < 0.01), AVNERP (from 246 +/- 47ms to 290 +/- 45ms, P < 0.01), AVNWCL (from 326 +/- 23ms to 388 +/- 42ms, P < 0.01) were seen. But no significant influence on SNRT, CSNRT and SACT (P < 0.05) were observed. Rotundium lengthened A-delta interval (from 97 +/- 18 ms to 106 +/- 19ms, P < 0.05) and the anterograde effective refractory period (ERP) of the accessory pathway (from 287 +/- 36ms to 320 +/- 43ms P < 0.05). It slightly lengthened V-A interval and the retrograde ERP of the accessory pathway. Rotundium lengthened AERP significantly (from 216 +/- 37ms to 244 +/- 41ms, P < 0.02). The effective rate of prevention of supraventricular tachycardia (SVT) by PES in this study was 77.8% (7/9). Rotundium showed no severe side effect in this study. PMID- 8200312 TI - [A study on congestive heart failure with ventricular arrhythmia and the catecholamine beta receptor system]. PMID- 8200313 TI - [The effect of ventricular pacing on plasma atrial natriuretic factor levels and its clinical significance]. AB - The effects of increasing pacing rate on cardiac hemodynamics and the release of atrial natriuretic factor (ANF), cGMP and cAMP were studied in 21 patients underwent ventricular pacing. ANF levels elevated insignificantly in patients without VA conduction, but elevated significantly in patients with VA conduction at pacing rate of 90,110 and 160 beat/min. The intracardiac pressure between these two groups of patients did not show significant difference. The conclusions are: (1) elevation of ANF levels at increasing pacing rate is mainly due to atrial distension rather than atrial pressure per se. (2) The elevation of ANF levels may reflect the changes of hemodynamics, the higher the ANF level, the more increase in intracardiac pressure. (3) marked elevation of ANF level may suggest presence of VA conduction in patients during ventricular pacing. PMID- 8200314 TI - [The relationship between nutrition and prevalence of coronary events and stroke in urban and rural areas of Shijiazhuang]. AB - The prevalence of coronary events was 64.5/100,000 in the urban of shijia zhuang and it was higher than 23.8/100,000 in rural. Contrary to the coronary events, the prevalence of stroke in urban (159.6/100,000) was lower than that in rural (170.2/100,000). The paradox was studied with their relation to nutrition. The SBP and DBP levels, hypertension rate, serum cholesterol, BMI and dietary saturated fatty acid and cholesterol in urban were higher than that in rural. They were risk factors especially to coronary events. The urban inhabitants had high animal protein intake and higher serum amino acids and higher SO4 excreted in daily urine than that of the rural inhabitants. The result suggests that the higher animal protein intake may be preventive factor for stroke in urban inhabitants. PMID- 8200315 TI - [Mechanism of the protective effects of berbamine on ischemia-reperfusion injury in isolated rat heart]. AB - Isolated perfused rat heart model was used to observe the protective effects of berbamine on myocardial ischemia/reperfusion injury. The hearts were remarkably injured by 40 min global ischemia followed by 20 min reperfusion. Berbamine could significantly improve heart function, prevent ventricular fibrillation, reduce CK release, preserve Na, K-ATPase activity, and reduce Na+ gain and K+ loss during ischemia and Ca2+ overload during reperfusion. With the use of low temperature ESR technique, we found that, in hearts subjected to 40 min ischemia and 15 sec reperfusion, oxygen-centered free radical signals became much more intense. In the presence of berbamine, these signals decreased. The results showed that berbamine could alleviate myocardial ischemia/reperfusion injury. This effect might be due to (1) preserved myocardial Na, K-ATPase activity and inhibition of sodium overload at the end of ischemia, which might further lead to attenuation of reperfusion-induced calcium overload, and (2) reduction of oxygen free radical generation during reperfusion. PMID- 8200316 TI - [A study on the protective effect of metallic chelators on ischemia-reperfusion injury of isolated rat heart]. AB - A Langendorff isolated rat heart preparation was used to determine the effect of the metallic chelators, deferoxamine and penicillamine on the extent of myocardial ischemia reperfusion injury. Each heart was subjected to 15-60 minutes of total ischemia at 37 degrees C followed by 15-60 minutes of reperfusion with either saline, deferoxamine (0.61 mmol/L), or penicillamine (30 mmol/L) treated perfusate. Reperfusion injury was assessed by the production of free radicals with electronic spin resonance spectroscopy and spin trap PBN, by the amount of creatine phospholipase released into the perfusate, by the changes in the myocardial vascular resistance, and by pathologic examination of myocardium. The results showed that the drug treated groups released significantly less radical adducts of PBN (P < 0.01) and creatine phosphokinase into the perfusate than the saline treated group (P < 0.01). The mean vascular resistance significantly increased in the saline treated group than in the drug treated groups (P < 0.01). Ultrastructural examination showed prominent attenuation of mitochondrial swelling in drug treated groups in comparison with the saline one. These findings indicated that both deferoxamine and penicillamine can protect the isolated rat heart from ischemia reperfusion injury. The possible mechanism of which is that metallic chelators block the transitional metal-catalyzed fenton reaction, and subsequently decrease the production of hydroxyl radical. PMID- 8200317 TI - [Biological determinants and prevention of coronary restenosis after angioplasty]. PMID- 8200318 TI - The relationship between age-related heart rate changes and developing brain function: a model of anencephalic human fetuses in utero. AB - We attempted to identify the brain segment which controls heart rate changes in human fetuses with advancing gestation. Twelve anencephalic and 165 normal fetuses (control-group fetuses) between 25-32 weeks' gestation were studied. The instantaneous fetal heart rate (FHR) data were obtained from each fetus for a continuous 90-120 min period, using an external cardiotocograph. Calculations included the 'individual probability distribution matrices' in which the FHRs at 1 beat/min intervals between 110 and 180 beats/min, the beat-to-beat differences (DFHRs) between +/- 5 beats/min and the probability values were arranged in rows, columns and the corresponding elements, respectively. Using 2-gestational-week intervals probability distribution matrices (age-group probability distribution matrices) obtained from 335 normal fetuses in our previous study as a reference, the difference between a given 'individual probability distribution matrix' and the corresponding age-group probability distribution matrix' was quantified as the 'difference rate' according to the formula in the text. From 25-26 to 27-28 weeks' gestation, the 'difference rates' in four anencephalic fetuses, with only the spinal cord preserved, were significantly higher in value than those of control-group fetuses, whereas the rates in four fetuses with both the spinal cord and medulla oblongata preserved, indicated no significant differences. From 29-30 to 31-32 weeks' gestation, the rates of the four fetuses with the spinal cord and medulla oblongata preserved, showed significant differences from the control-group fetuses. These findings suggest that there is a critical period between 27-28 and 29-30 weeks' gestation with regard to the developing brain function pertaining to FHR changes. In the early stage, the medulla oblongata plays a role in FHR changes, whereas, in the latter stage, the brain cephalad to the medulla also appears to take on the role of FHR regulator. PMID- 8200319 TI - Dramatic increase in levels of placental protein 14 in amniotic fluid at 10-15 weeks' pregnancy. AB - Concentrations of placental protein 14 (PP14) were measured by radioimmunoassay in 103 amniotic fluid samples from 10 to 20 weeks of pregnancy. Low levels of PP14 were present at 10-12 weeks (median values 82-280 micrograms/l). After 12 weeks, the levels increased by two orders of magnitude to reach a peak at 18 weeks (median 11 mg/l). This pattern may reflect the obliteration of the extraembryonic coelom and direct apposition of the decidua with the chorio amnion. PMID- 8200320 TI - The development of circadian rhythmicity in neonates. AB - Eleven healthy, full-term babies were studied on the second day (d2) after birth and again 4 weeks (w4) later. The babies lived in natural lighting conditions and were fed every 4 h. Blood pressure, heart rate, skin (abdomen) and rectal temperatures were measured at 10-min intervals for 24 h. Behavioural states (deep sleep, light sleep, drowsy, alert, crying) were measured at the same times, and used to purify the raw data. Both the raw and purified data were assessed for circadian (24-h) rhythmicity by cosinor analysis. Circadian rhythms in heart rate and blood pressure were poorly developed at d2 and w4. By contrast, skin and rectal temperatures showed circadian rhythmicity that increased in amplitude between d2 and w4; this increase was seen in both raw and purified data. The masking effect due to sleep changed also; the depression caused by "deep sleep" became greater between d2 and w4. The results indicate that the development of circadian rhythmicity in body temperature was not secondary to that of a circadian pattern of sleep and activity, and presumably derives from a body clock that is beginning to develop independently. PMID- 8200321 TI - Patterns of breathing movements in the near-term human fetus: relationship to behavioural states. AB - The occurrence of fetal breathing movements was studied in relation to fetal behavioural states 1F and 2F, as recognized by the heart rate patterns A and B, respectively. Simultaneous recordings of fetal heart rate and body, eye and breathing movements were available for analysis (n = 88). These recordings, lasting > or = 2 h, had been made in healthy near-term fetuses during the afternoon or evening, starting about 1 h after the maternal meal. In the majority of recordings fetal breathing activity was lower during heart rate pattern A than during pattern B, but as the opposite occurred in 29/88 recordings (33%), the interstate difference was not significant (P = 0.052). Detailed analysis revealed that breathing movements were more numerous during pattern B than during pattern A if the incidence of breathing during a particular time period was low (30-40% of time). At a high overall breathing incidence (> 40%), however, breathing movements were more often present during pattern A than during pattern B. The latter occurred especially in the first hour of recording, i.e. less distant in time from maternal meals. We conclude that fetal breathing activity is generally higher during state 2F than during state 1F, but a clear-cut state-dependency is absent. Secondly, the relationship between the incidences of breathing during states 1F and 2F depends on the 'drive' or motivation (presumably the blood glucose content) to breathe. PMID- 8200322 TI - Abnormal motor behaviour and developmental postmortem findings in a fetus with Fanconi anaemia. AB - Prenatal diagnosis in the third pregnancy of a mother who already had one healthy son and one son with Fanconi anaemia (FA), revealed that her fetus was also affected with FA. At 22 weeks a maternal complaint about excessive fetal kicking starting at 15 weeks, focused our attention on the behaviour of the fetus, which was observed by means of real-time ultrasound for 30 min. The differentiation of specific movement patterns was strongly diminished. The qualitative expression of general movements was considered to be consistently abnormal due to the fact that they were performed with large amplitudes, high speed and abrupt onsets. The incidence of general movements was within the normal range, however, the distribution in the burst-pause pattern was abnormal. Postmortem examination showed a spongy myelinopathy of the central nervous system that may account for the abnormal motor activity. This combination of findings has not been previously reported in association with FA. PMID- 8200323 TI - The aetiology of cerebral palsy. AB - I have attempted to give an overview of the latest thoughts on the aetiology of the cerebral palsies. These motor disabilities are of continuing interest and their prevalence is rising, particularly in low birth weight preterm singletons and multiple births. The likely multiplicity of causes demands intelligent investigation probably in collaborative population data bases. Ultrasound and other scans may provide better data on both site and timing of neonatal brain damage. However these are more likely to have been done on cerebral palsied children who were preterm than on those born at term. There are currently no clear preventive messages except those relating to postnatal cerebral palsy or encouraging strategies to reverse the increases in multiple births. The challenges now are to obtain better data on the antenatal factors and on causal sequences which may be important. The Little Foundation is seeking to encourage such collaborative studies. Other suggestions from our workshop [14] included attempting to follow up those infants who have been participants in large randomised controlled trials (such as those evaluating surfactant) to the age when they can be confidently diagnosed as having cerebral palsy. If antenatal data have been collected on them they may form the basis for a cohort analysis relating risk to cerebral palsy occurrence, as well as to answer questions about whether the intervention influenced cerebral palsy occurrence. PMID- 8200324 TI - Finger movements and fingers postures in pre-term infants are not a good indicator of brain damage. AB - The aim of the study was to analyse, with a more detailed classification the occurrence of movements and postures of the fingers in normal and brain damaged pre-term infants. To this end the same videorecordings of normal subjects of the study described by Cioni and Prechtl and those with defined brain lesions from the investigation by Ferrari et al. have been reanalysed. In three general movements, selected randomly from each infant, we assessed the finger movement. There was no systematic trend with age and the repertoire of finger patterns per observation varied between different individuals. Only one or two finger(s) move (pattern B) and synchronized finger opening-closing (pattern D) and the complex and variable movement of three or more fingers (pattern E) are all more often or even only seen during arm movements. Fisting without arm movement (pattern A-) was only seen less frequently in the control cases, in the infants with flares and one-sided lesions. On the other hand, the two latter groups had more often pattern C+ (opening of all fingers with arm movement) while B+ (only one or two fingers move with arm movement) and E+ (three or more fingers move variably with arm movement) was less frequent in the severely damaged infants. Albeit significant differences, the plotted data immediately show the large overlap of the findings between the groups. There was no difference in the fisting between low-risk and neurologically abnormal pre-term infants. These findings corroborate the conclusions that abnormal movements and postures are not useful in the diagnosis of pre-term infants with confirmed brain lesions because of the wide overlap between the values for normal and brain damaged infants. PMID- 8200325 TI - Nutrition and the epidemiology of cataract and age-related maculopathy. PMID- 8200326 TI - Is diet an independent risk factor for mortality? 20 year mortality in the Italian rural cohorts of the Seven Countries Study. AB - The relation of diet to mortality is examined using the data of the Italian rural cohorts of the Seven Countries Study, a prospective investigation of factors related to cardiovascular disease. The present analysis includes 1536 men aged 45 64 years, whose dietary habits and food consumption, including alcoholic beverages, were measured in 1965. Of the 1536, 668 (43.5%) died during a follow up period of 20 years. Large differences in survival probabilities were observed for different dietary patterns (i.e. for different intakes of energy and nutrients). The dietary pattern that corresponded to the lowest mortality rate (27% after 20 years) was: more than 2800 kcal/d (11.7 MJ/d), with more than 41% of the calories coming from carbohydrates, more than 9% from proteins, between 16% and 23% from unsaturated lipids, and between 13% and 19% from alcohol. As the number of disagreements from the previous conditions increases, the mortality rate increases to reach 69% in 20 years in the worst case. Differences in mortality persisted after adjustment for confounders and some major established mortality risk factors. PMID- 8200327 TI - Plasma norepinephrine kinetics are unaltered in chronically undernourished adult subjects. AB - Twelve healthy adults divided into a well-nourished (WN; n = 6) and a chronically energy deficient (CED; n = 6) groups underwent a single 30 min infusion of norepinephrine (NE) administered at the rate of 0.15 micrograms/kg fat-free mass/min. Measured parameters in the basal state and during the infusion included heart rate (by electrocardiograph), stroke volume, cardiac output and other cardiac indices (by impedance cardiography) and blood pressure recordings. The data are suggestive of fairly similar cardiovascular responses in the CED and WN subjects, with the exception of cardiac inotropy (i.e. strength of cardiac muscle contractility) and changes in total peripheral resistance, both of which were enhanced in the CED. Peak NE levels of both groups during the infusion were similar and so was the clearance rate for NE corrected for fat-free mass differences. Although plasma half-life of NE tended to be higher in the CED group, plasma appearance rates of NE were comparable between the groups, suggesting that plasma NE kinetics were not altered in CED adults. PMID- 8200328 TI - Nutritional status and early warning of mortality in southern Ethiopia, 1988 1991. AB - OBJECTIVE: Ethiopian Government guidelines on nutritional survey data and relief provision call for intervention once mean weight-for-length (W/L) in an area falls below 90% of reference, on the basis that mortality is unlikely to rise until this level is reached. In this paper the appropriateness of the 90% cut-off is examined using data from Wolayita, southern Ethiopia. SURVEY DESIGN AND SUBJECTS: Fifteen to 25 villages are selected at random for survey each year, with all children 70-110 cm in length being followed up every 2 months. During the 3 years covered by these analyses 21,701 W/L measurements were made on 5455 children from 65 villages. 126 of the children died. RESULTS: In the first and third survey years, rapid declines in mean W/L were recorded, with mortality increasing very roughly three-fold (compared to year 2, P < 0.01), even though mean W/L remained at or above 90% of reference at all times. A logistic regression analysis relating mortality to W/L indicates that between 20% and 35% of the greater mortality in years 1 and 3 can be explained by the observed changes in W/L. The remainder occurred because of an increase in underlying or background risk (which might perhaps be expected in the circumstances of generally deteriorating nutritional status). CONCLUSIONS: The results suggest that child mortality is likely to increase before area mean W/L falls to 90% of reference, indicating that emergency interventions should be triggered earlier than at present. PMID- 8200329 TI - Relationship between urinary iodine concentration and hearing capacity in children. AB - Urinary iodine excretion was assessed in 1222 healthy children aged 10 months (n = 456), 2 years (n = 368) and 4 years (n = 398) living in the Paris area and originating from continental France (55.2%), North Africa (15.7%), the West Indies (9.7%), West Africa (8.2%), Southeast Asia (5.5%), and southern Europe (5.7%). Iodine excretions (median values) were, respectively, 18.1, 13.4 and 11.6 micrograms/100 ml at 10 months, 2 years and 4 years, and risk of mild to moderate iodine deficiency (< 10 micrograms/100 ml) was 18.0%, 32.3% and 37.2% for the same age groups. Urinary iodine excretion was highest among Southeast Asian children, and lowest among West Africans. Hearing acuity was measured either by conventional mono-aural pure-tone audiometry or by binaural free field testing depending on the child's age. Hearing loss at 4000 Hz and average hearing impairment at speech frequencies (500, 1000 and 2000 Hz) were more severe among children at risk of mild to moderate iodine deficiency (less than 10 micrograms/100 ml) compared with those with urinary excretion above 10 micrograms/100 ml. PMID- 8200330 TI - Nutritional assessment: the problem of clinical-anthropometrical mismatch. AB - OBJECTIVE: To study risk factors for and prevalence and validity of clinical anthropometrical mismatch (CAM) defined as the presence of clinical signs of protein-energy malnutrition despite normal weight-for-age (WFA). DESIGN: A semi longitudinal study of nutrition and morbidity with a longitudinal assessment of mortality. SETTING: The rural health zone of Bwamanda in Northern Zaire. SUBJECTS: 4238 children of age 0-6 years enrolled by random cluster sampling. INTERVENTION: Clinical nutritional staging, anthropometry, diagnosis of diarrhoea and severe respiratory infection in the rainy (first survey) and the subsequent dry season (second survey). Recording of mortality during 27 months after the second survey. RESULTS: Prevalence of CAM was high above various cut-off levels of WFA and was accompanied by increased morbidity and long-term mortality. Of all the children with clinical signs of malnutrition, a high proportion had normal WFA. CAM was associated with weight loss within the limits of the international reference. CONCLUSIONS: If a child has a normal weight but clinical malnutrition signs are present, the clinical diagnosis should prevail. Weight charts are not fully appropriate for nutritional classification purposes. The clinical nutritional staging used in this study is sufficiently reproducible and capable of identifying children with functional malnutrition. PMID- 8200331 TI - Daily variation in food and nutrient intakes of Asian children in Sheffield. AB - Weighed intake data from a 1 year cross-sectional nutritional survey of Indo Asian children (4-40 months of age), in Sheffield, were analysed with respect to the day-to-day variability of energy and selected nutrient intakes. 117 children (i.e. 53% of those approached) completed studies; this figure approximates one quarter of the estimated target population. The between- and within-subject variability in dietary intakes was examined according to age group. For energy, the between-subject variability, measured by the coefficient of variation between subjects (CVb) rose from 26% at 4- < 12 months to 36% in the 12- < 24 month group. Within subject variation (CVw) for energy varied little between age groups (23-29%). Within-subject variability in protein and fat intakes showed a similar pattern to that of energy. However, the CVb for protein was maximal in the youngest group; it was lower than the CVw in the over 24 month group. Iron and vitamin C intakes were subject to much higher levels of within- and between subject variation; the CVb for iron was maximal in the 12- < 24m group. Although the within-person variation was demonstrably greater than that of Caucasian infants (A. E. Black et al., 1983, Hum. Nutr.: Appl. Nutr. 37A, 448-458), the between-person variation, as measured over a 1 year period, was also high and comparatively larger than the CVw.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200332 TI - Orange juice enhances aluminium absorption from antacid preparation. AB - Aluminium absorption from four doses of the antacid preparation 'Aludrox' when taken alone, with orange juice or with milk was compared by measuring the change in urinary aluminium following Aludrox dosage in 15 normal adults. There was an approximately 10-fold increase in 24 h urinary aluminium excretion following the Aludrox plus orange juice (232 micrograms) which was significantly higher than that following Aludrox alone (62 micrograms) (P < 0.001), but milk had no effect on aluminium absorption. The results showed that orange juice greatly enhanced aluminium absorption and should not therefore be taken in conjunction with aluminium-containing antacid preparations. PMID- 8200333 TI - Energy restriction decreases number of circulating natural killer cells and serum levels of immunoglobulins in overweight women. AB - We examined the effects of energy restriction on immune response and also compared the effects of low fat (LF, 18.6 E%) and high fat (HF, 40.7 E%) diets during energy restriction on immunological parameters. Ten overweight women were fed the HF diet for 42 days (P1) to maintain their body weights. For the next 84 days (P2), the energy intake was reduced to 50% of the intake during P1 for all the women, five of them were fed the HF diet and the other five the LF diet. For the last 35 days of the study (P3), subjects remained on their respective diets, but the energy intake was increased to maintain BW to the level reached at the end of energy restriction. Serum concentrations of IgG, IgA, IgM, C3 and C4, numbers of lymphocytes and their subsets, blastogenesis of peripheral blood mononuclear cells cultured with phytohemagglutinin, concanavalin A and protein A were determined several times during the study. Delayed hypersensitivity skin (DHS) response to seven recall antigens was determined towards the end of each study period. None of the parameters studied were different between the HF and LF dietary groups. During energy restriction the subjects lost an average of 7 kg in the LF group and 9 kg in the HF group. Energy restriction caused a significant (P < 0.005) decrease in the serum concentration of IgG, IgA, C3, and the number of circulating natural killer (NK) cells. An increase in energy intake during P3 reversed some of the decreases caused by energy restriction, but the levels did not return to pre-restriction levels during these 35 days of refeeding adequate dietary energy. The numbers of circulating lymphocytes and their subsets with the exception of NK cells, serum levels of IgM and C4, and the DHS response monitored 48 h after the application of antigens were not affected by energy restriction. Health status of the women in our study did not seem to be compromised; however, it could be compromised under more drastic restrictions or with moderate restrictions in high risk subjects. PMID- 8200334 TI - The process of cellular uptake of iron from transferrin. A computer simulation program. AB - In an attempt to improve our understanding of the complex interplay between cell compartments and chemical species during cellular uptake of iron from transferrin, we designed a computer simulation program based on current models of receptor-mediated endocytosis and pinocytosis. The program calculates and visualizes, as a function of time, the changes in transferrin, apotransferrin, and iron concentrations occurring in all relevant cellular compartments during cellular iron acquisition from transferrin. Simulation of literature data showed that the program generates results that are in accordance with experimental data. Furthermore, from measurements of the uptake of [carboxyl-14C]dextran we could utilize the program to suggest rate constants characteristic for the pinocytic process in rat reticulocytes. Moreover, simulations indicate that the apparent difference in the iron uptake process observed between reticulocytes and hepatocytes may be explained by the contribution made by pinocytosis to the iron uptake process. Finally, the present program should have potential as an educational tool during introduction to the field of receptor-mediated endocytosis in general and to cellular iron metabolism in particular. PMID- 8200335 TI - Two functionally distinct half sites in the DNA-recognition sequence of the Myb oncoprotein. AB - The oncoprotein Myb is a sequence-specific DNA-binding protein with a pivotal function in the development and proliferation of hematopoietic precursor cells. A minimal DNA-binding domain composed of two tryptophan-rich repeats R2 and R3 is responsible for sequence recognition. Based on model building and mutational analysis, Myb was proposed to recognise its target through a double helix-turn helix (HTH)-related motif using two recognition helices, one in R2 and one in R3. We found, by mutational analysis, that the DNA-binding site for c-Myb is functionally bipartite. While the first half site is dominant and absolutely required for binding, the second half site is only modulatory and mainly affects the half life of the complex. This bipartite nature of the binding site parallels the proposed bipartite structure of R2R3 with two HTH-related domains. Analysis of the DNA-binding site of R2R3 by missing-base interference-footprint analysis showed that the protein interacted with a 9-bp region. The same was found with a larger protein containing all three repeats. The effect of adding R1 was mainly to stabilise the complex. The borders of the complex, as revealed by exonuclease III footprinting, did not change due to the presence of R1. However, both borders became more refractory to the nuclease when R1 was present, but with a difference that suggested a specific orientation of the repeat domains relative to the DNA binding site. We propose that the first half site is recognised by R3, while the second modulatory half site interacts with the R2 repeat. PMID- 8200336 TI - Site-directed mutagenesis of cysteine residues of hepatitis B surface antigen. Analysis of two single mutants and the double mutant. AB - The structure of hepatitis B surface antigen (HBsAg) is mainly maintained by an intricate disulfide network responsible for most of its structural and antigenic properties. Characterization of three cysteine-replacement mutants of HBsAg has been performed by both structural and immunological methods. Replacement of Cys121 or Cys124 with serine results in mutant proteins that show diminished binding titres to both monoclonal antibodies and to a polyclonal serum, indicating that a structural change has taken place. Circular dichroism analysis shows that the substitution of either of these two residues also diminishes the helical content of the protein. However, the double mutant, in which both cysteine residues have been simultaneously changed, reverts the properties of the single mutations, and shows similar behaviour to the wild-type protein. Both the single and double cysteine mutants are efficiently glycosylated and secreted from Chinese hamster ovary cells and, in all cases, the mutant proteins assemble into spherical particles of similar buoyant density to both the wild-type and serum derived HBsAg. PMID- 8200337 TI - Purification and characterization of an extracellular enzyme from Streptomyces antibioticus that converts inactive glycosylated oleandomycin into the active antibiotic. AB - Cell-free extracts from the oleandomycin producer, Streptomyces antibioticus, possess an intracellular glycosyltransferase capable of inactivating oleandomycin by glycosylation of the 2'-hydroxyl group in the desosamine moiety of the molecule [Vilches, C., Hernandez, C., Mendez, C. & Salas, J. A. (1992) J. Bacteriol. 174, 161-165]. Using a four-step purification procedure, we have purified an enzyme activity from the culture supernatants from this organism which is able to release glucose from the inactive glycosylated molecule thus reactivating the antibiotic activity. This enzyme activity appeared in the culture supernatants immediately before oleandomycin is detected. The enzyme (molecular mass 87 kDa) showed a high degree of substrate specificity, not acting on other glycosylated macrolides such as methymycin, lankamycin and rosaramicin which are substrates for the glycosyltransferase. A second activity was detected corresponding to a 34-kDa polypeptide which probably originates from proteolytic cleavage of the larger polypeptide. The 87-kDa polypeptide possibly catalyses the last biosynthetic step in oleandomycin biosynthesis by S. antibioticus. PMID- 8200338 TI - Characterization of a polyhistidine-tagged form of human myristoyl-CoA: protein N myristoyltransferase produced in Escherichia coli. AB - The enzyme myristoyl-CoA:protein N-myristoyltransferase is responsible for the attachment of a myristoyl group to the N-terminal glycine of a number of cell, viral and fungal proteins. In order to overcome the difficulties of purification of this enzyme from tissue sources, we have produced an N-terminally polyhistidine-tagged version of the enzyme and expressed this in Escherichia coli. The resulting enzyme has a molecular mass of 53 kDa and is fully active showing the expected specificity for myristic acid and causing the N-terminal myristoylation of both synthetic peptide and protein substrates in vitro. The enzyme exhibits a broad pH optimum peaking at a pH of 8.0 and has a Km for myristoyl-CoA of 7.6 microM. The two synthetic peptide substrates based on the N terminal sequence of the catalytic subunit of protein kinase A (GNAAAARR) and of p60src (GSSKSKPKDPSQRRRY) have different kinetic parameters with Km values of 115.2 microM and 44.2 microM and Vmax values of 95 and 120 nmol.min-1.mg-1, respectively. The expressed enzyme is partially inhibited (50%) by iodoacetamide at 5 mM and fully inhibited by diethylpyrocarbonate at 10 mM. This latter inhibition can be prevented by including histidine in the incubation of the enzyme and inhibitor. Antisera raised to synthetic peptides based on sequences derived from the N- and C- terminus of the human enzyme reacted with the expressed protein on Western blots, but only the N-terminal sequence reacted with the native protein suggesting that the C-terminus may be not be accessible. The enzyme can catalyse the removal of a myristoyl group from myristoylated peptides but does so only in the presence of added coenzyme A. PMID- 8200339 TI - Analysis of cytochrome-b amino acid residues forming the contact face with the iron-sulfur subunit of ubiquinol:cytochrome-c reductase in Saccharomyces cerevisiae. AB - Four mutations in the mitochondrial cytochrome b of Saccharomyces cerevisiae have been characterized with respect to catalytic properties, inhibitor resistance and subunit interaction. The respiratory-deficient mutant [G137E]cytochrome b and the pseudo-wild-type revertant [G137E, N256K]cytochrome b were described previously [di Rago, J.-P., Netter, P. & Slonimski, P. P. (1990) J. Biol. Chem. 265, 3332 3339; di Rago, J.-P., Netter, P. & Slonimski, P. P. (1990) J. Biol. Chem. 265, 15750-15757]. Two new mutants [N256K]cytochrome b and [N256I]cytochrome b were isolated by dissociation of the second-site suppressor from the original target mutation. The mutants [G137E]cytochrome b and [G137E, N256K]cytochrome b exhibited a high resistance against methoxyacrylate inhibitors, whereas the suppressors [N256K]cytochrome b and [N256I]cytochrome b showed only a slight resistance. Remarkably, all mutants exhibited stigmatellin cross-resistance. The electron-transfer activity from the substrate nonylubiquinol to cytochrome c of mitochondrial membranes was diminished in all mutants. The substitution G137-->E decreases Vmax/Km by one order of magnitude, indicating a reduced catalytic efficiency for ubiquinol. The amino acid exchange at position 256 to a positively charged lysine residue or to a hydrophobic isoleucine residue resulted mainly in a diminished specific activity. The iron-sulfur subunit and the 8.5-kDa subunit were detectable in all mutants at normal levels in immunoblots of membrane preparations, indicating proper assembly of the complex. However, after purification, the mutant bc1 complex lacked the iron-sulfur subunit and the 8.5 kDa subunit. In contrast, the iron-sulfur subunit can only be dissociated from the parental bc1 complex by harsh treatment. These data suggest that residues 137 and 256 in cytochrome b are crucial for cytochrome-b/iron-sulfur protein interaction. PMID- 8200340 TI - Identification of two antibody-interaction sites on the surface of Panulirus interruptus hemocyanin. AB - Negatively stained complexes of Panulirus interruptus (spiny lobster) hemocyanin with two different monoclonal antibodies, named E and J, were studied by electron microscopy and image processing. The attachment site of the antibodies to the hexameric hemocyanin molecule was deduced from two perpendicular views of hemocyanin/antibody complexes, in which either the threefold axis or one of the twofold axes was oriented perpendicular to the supporting film. Images of complexes in these orientations were searched with reference images simulated from the known X-ray structure of P. interruptus hemocyanin. The two sites were further characterized by combining our results from electron microscopy with structural data obtained by X-ray diffraction and other methods. These two antibodies recognize different non-overlapping epitopes. The epitope for clone E is located on domain 3 at the surface of the beta barrel and consists of certain loops, which form connections between beta-strand structures. The epitope for clone J is situated on domain 1 at the surface of an alpha-helical region and consists mainly of certain alpha-helices connecting loops. The orientation of the hemocyanin hexamers in the two complexes is very different, as is demonstrated most clearly when they form chains. Clone E forms complexes with the threefold axes perpendicular to the chain direction, while for clone J the threefold axes seem to be parallel to the main direction. The angle between the Fab part of an IgG molecule and the threefold axis of the hexamer is 60 +/- 5 degrees for clone E and 35 +/- 7 degrees for clone J. This observation is clearly related to the difference in orientation of the hexamers for the two complexes. PMID- 8200341 TI - The magnesium-GTP interaction in microtubule assembly. AB - Microtubule-associated-protein-dependent assembly of tubulin with GDP in the exchangeable site (tubulin-GDP) can occur with minimal free Mg2+ (< 3 microM). This reaction is totally inhibited by EDTA and by GTP concentrations over 2 mM and stimulated by MgCl2. Quantitative aspects of this stimulation are affected by both the Mg2+ and GTP concentrations but no relationship exists between reaction rates and relative amounts of different magnesium and GTP species. GTP binding to tubulin-GDP, while maximally stimulated 2-3-fold by exogenous MgCl2, was inhibited less than 50% by EDTA, and the amount of GTP bound increased as its concentration rose to levels that inhibited polymerization. Studies on the binding of Mg2+ to tubulin-GDP in the presence and absence of GTP showed that the increase in the amount of tubulin-associated Mg2+ was substoichiometric to the amount of GTP bound (maximum stoichiometry of additional Mg2+ to GTP bound, 0.7). Upon polymerization the increased Mg2+ content of tubulin was reduced, indicating its loss during GTP hydrolysis. Mg2+ thus plays a critical role in assembly distinct from its enhancement of GTP binding to the exchangeable site. If magnesium is present in trace amounts, this role must either be catalytic during polymerization or limited to nucleation. PMID- 8200342 TI - Solid-phase synthesis, conformational analysis and in vitro cleavage of synthetic human synaptobrevin II 1-93 by tetanus toxin L chain. AB - A 93-residue peptide corresponding to the cytosolic domain of a human vesicle associated membrane protein (VAMP or synaptobrevin) has been prepared by solid phase peptide synthesis in order to investigate the proteolytic activity of the tetanus toxin light chain (TeTx L chain). This protein has been recently reported to inactivate the neuronal rat synaptobrevin II by proteolysis. We show in this study that the synthetic human synaptobrevin II 1-93 (Syb II 1-93) as well as an N-terminus-shortened 69-residue peptide (Syb II 25-93) were cleaved selectively at the Gln76-Phe77 peptide bond by TeTx L chain while shorter peptides were not. A Michaelis constant Km = 192 +/- 2 microM and a catalytic constant kcat = 0.5 min-1 were found for the 93-residue peptide. A neutral optimum pH for the cleavage rate, an inhibition by preincubation of the toxin with well known nonspecific inhibitors of metallopeptidases as well as a zinc-dependent enzyme activity suggest that TeTx belongs to the zinc endopeptidase family. Moreover an activation by reducing agents and an inhibition by cysteine-modifying chemical reagents indicate a critical thiol dependency. Among several specific inhibitors of zinc endopeptidases tested, none could inhibit TeTx L chain even at high concentration. Structural studies by 600-MHz 1H-NMR showed that in water or dimethylsulfoxide the peptide Syb II 1-93 and shorter fragments did not present well defined conformations. Nevertheless protein-protein interactions have been shown for the peptides Syb II 1-93 and 25-93 but not for Syb II 51-93, a fragment not cleaved by TeTx L chain. PMID- 8200343 TI - Quantification of two splicing events in the L-type calcium channel alpha-1 subunit of intestinal smooth muscle and other tissues. AB - cDNA fragments encoding a representative region of the L-type calcium channel alpha-1 subunit of rabbit intestine smooth muscle were amplified by polymerase chain reaction (PCR). The nucleotide sequences of these intestine clones shared a high similarity with aorta, lung and heart calcium channels. However, in the extracellular loop between the third and fourth segments of domain IV and in the transmembrane IVS3 segment itself, we observed primary sequence variations corresponding to alternative splicing phenomenons. Since structural differences of L-type calcium channel alpha-1 subunits could result in functional variations, the respective expression frequency of these isoforms was determined in various tissues and species, and in the embryonic A7r5 cell line. The ontogeny of these splicing events was also examined from tissues of different ages. From this quantitative study, carried out by PCR of reverse-transcribed mRNA, it clearly appears that the observed splicing processes in the IVS3-IVS4 region are not only tissue-dependent but also regulated during development. PMID- 8200344 TI - Cation binding to a Bacillus (1,3-1,4)-beta-glucanase. Geometry, affinity and effect on protein stability. AB - The hybrid Bacillus (1,3-1,4)-beta-glucanase H(A16-M), consisting of 16 N terminal amino acids derived from the mature form of the B. amyloliquefaciens enzyme and of 198 C-proximal amino acids from the B. macerans enzyme, binds a calcium ion at a site at its molecular surface remote from the active center [T. Keitel, O. Simon, R. Borriss & U. Heinemann (1993) Proc. Natl Acad. Sci. USA 90, 5287-5291]. X-ray diffraction analysis at 0.22-nm resolution of crystals grown in the absence of calcium and in the presence of EDTA shows this site to be occupied by a sodium ion. Whereas the calcium ion has six oxygen atoms in its coordination sphere, two of which are from water molecules, sodium is fivefold coordinated with a fifth ligand belonging to a symmetry-related protein molecule in the crystal lattice. The affinity of H(A16-M) for calcium over sodium has been determined calorimetrically. Calcium binding stabilizes the native three dimensional structure of the protein as shown by guanidinium chloride unfolding and thermal inactivation experiments. The enhanced enzymic activity of Bacillus beta-glucanases at elevated temperatures in the presence of calcium ions is attributed to a general stabilizing effect by the cation. PMID- 8200345 TI - Calcium and magnesium binding to rat parvalbumin. AB - Ca2+ and Mg2+ binding to rat parvalbumin was measured by means of the fluorescent Ca2+ indicator fluo-3 using a method developed earlier [Eberhard, M. & Erne, P. (1991) Eur. J. Biochem. 202, 1333-1338]. We demonstrate that rat parvalbumin contains two equivalent Ca2+/Mg2+ binding sites and that Ca2+ and Mg2+ compete for the same sites. Dissociation constants (Kd) for Ca2+ and Mg2+ in Hepes buffer containing 150 mM K+ at 35 degrees C and pH 7.2 are 11.0 +/- 1.8 nM and 41 +/- 8 microM, respectively. At an ionic strength below 0.2 M, Kd values of Ca2+ binding to rat parvalbumin are approximately proportional to the ion concentration. Kd values of Ca2+ binding were found to be about fourfold larger in the presence of Na+ as compared with K+, indicating that Na+ distinctly influences Ca2+ binding to rat parvalbumin. Both Ca2+ and Mg2+ binding to parvalbumin are exothermic whereas Ca2+ and Mg2+ binding to fluo-3 are endothermic entropy-driven processes. PMID- 8200346 TI - Yolk granules are the major compartment for bullfrog (Rana catesbeiana) oocyte specific ribonuclease. AB - Rana catesbeiana ribonuclease (RC-RNase) is a pyrimidine guanine sequence specific ribonuclease found only in R. catesbeiana (bullfrog) oocytes, not in other organs. An immunohistochemical assay showed that RC-RNase was present in the regular yolk granules, but not in forming yolk granules, yolk platelets, pigment granules, mitochondria clouds or the nucleus. The RC-RNase was restricted to the lateral amorphous area of the yolk granules, and was absent from the central area that has a vitellogenin crystal lattice. The RC-RNase was extracted from yolk granules by 0.5 M NaCl and purified by dialysis and affinity chromatography. Most of the RC-RNase (94%) was found in the yolk granules, the rest RC-RNase (6%) was found in the cytosol in the form of free RNase and latent RNase. The RC-RNase extracted from yolk granules was further analyzed by immunoprecipitation and RNase activity assay on an SDS/polyacrylamide gel. Our results suggest that the RC-RNase activity is regulated by both compartmentation and inhibitor binding. PMID- 8200347 TI - Molecular cloning and amino acid sequence of the porcine 17 beta-estradiol dehydrogenase. AB - We describe the cloning and sequencing of porcine 17 beta-estradiol dehydrogenase. The enzyme performs oxidation 360-fold more efficiently than reduction, both measured under optimal conditions. It is localized in specialized vesicles of epithelial cells. The cDNA clones were isolated from a lambda UNI ZAP XR library of porcine kidney and polymerase-chain-reaction-amplified from templates of uterus epithelium. In both tissues, the same enzyme is coded by a transcript of 2.9 kb. It contains a 69-b 5'-noncoding region, an open reading frame of 2211 b and a 3'-noncoding region of 624 b. The open reading frame of 737 amino acids with a predicted molecular mass 79,973 Da was confirmed by amino acid sequencing of peptides. The 80-kDa translation product is processed to the N terminal 32-kDa enzyme, part of which is then covalently linked to actin. The estradiol dehydrogenase/actin complex and the 80-kDa translation product comigrate in SDS/PAGE. PMID- 8200348 TI - Inositol 1,4,5-trisphosphate activates receptor-mediated calcium entry by two different pathways in hepatocytes. AB - The quenching of fura-2 fluorescence by the influx of extracellular Mn2+ was measured to indicate the flux rates through receptor-operated calcium channels in the plasma membrane of rat hepatocytes. Neomycin, an inhibitor of phospholipase C, inhibited the vasopressin-induced influx of Mn2+. Thus, the agonist-induced entry of extracellular calcium into hepatocytes is linked to a phospholipase C generated second messenger. Microinjection of inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4], inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] or 3-deoxy-3-fluoro Ins(1,4,5)P3 revealed that Ins(1,4,5)P3 rather than Ins(1,3,4,5)P4 is responsible for calcium entry. The activation of phospholipase C by vasopressin produced an influx of Mn2+ independent of the depletion of intracellular calcium stores if this depletion was delayed by the Ins(1,4,5)P3 receptor antagonist heparin or by the use of a low agonist concentration. Thapsigargin, an inhibitor of the store calcium pump, leading to an Ins(1,4,5)P3-independent emptying of stores, gave a short living signal (less than 3 min) for calcium entry. We propose that Ins(1,4,5)P3 is able to stimulate calcium entry by two pathways. (a) Ins(1,4,5)P3 activates receptor-operated calcium channels in a direct manner. The calcium entry resulting from this is followed (b) by the Ins(1,4,5)P3-induced depletion of calcium stores, producing a store-dependent entry. PMID- 8200349 TI - The NAM1 protein (NAM1p), which is selectively required for cox1, cytb and atp6 transcript processing/stabilisation, is located in the yeast mitochondrial matrix. AB - The NAM1 nuclear gene was shown to control the stability and/or processing of mitochondrial transcripts of the cytochrome b, cytochrome oxidase subunit I and ATP synthase subunit VI genes [Groudinsky O., Bousquet I., Wallis M. G., Slonimski, P. P. & Dujardin G. (1993) Mol. Gen. Genet. 240, 419-427]. In order to better understand the mode of action of the NAM1 gene product, we have examined its intracellular fate. A fusion plasmid enabling bacterial over-expression of the corresponding protein-A-NAM1 cognate was constructed and subsequently employed as an antigen to raise polyclonal antibodies. These antibodies specifically recognise a 50-kDa protein which purifies along with the mitochondria and corresponds to NAM1p. Submitochondrial localisation experiments show that NAM1p is a soluble protein, located interior to the mitoplasts. Matricial location is a strong argument in favour of a direct interaction of NAM1p with particular mitochondrial transcripts and leads us to propose a model in which NAM1p could be an RNA-convoying protein stabilising and directing mitochondrial transcripts towards the inner face of the inner membrane where translation and assembly seem to occur. PMID- 8200350 TI - Purification of Golgi adaptor protein 1 from bovine adrenal gland and characterization of its beta 1 (beta') subunit by microsequencing. AB - A method for the purification of the Golgi adaptor protein 1 from bovine adrenal gland tissue was devised to investigate the relationship of its beta 1 (formerly referred to as beta') subunit to known beta-type sequences. Adrenal gland tissue was chosen for this study because it yielded 2-3 times more adaptor protein 1 than a comparable preparation from bovine brain. Like its neuronal isoform, the beta 1 subunit from adrenal gland adaptor protein 1 is readily cleaved by trypsin into a 63-kDa N-terminal fragment and a 40-kDa C-terminal fragment, while the gamma subunit is largely refractory to digestion. Based on microsequencing of 167 residues from the 63-kDa fragment, we noted 11 differences to the corresponding region of the beta 2 (formerly beta) subunit of the plasma membrane adaptor protein 2, but only one difference to the corresponding region of a beta-type protein encoded by the rat cDNA clone AP105a which is supposed to be a variant of the beta 2 subunit of the plasma membrane adaptor protein 2 [Kirchhausen, T., Nathanson, K. L., Matsui, W., Vaisberg, A., Chow, E. P., Burne, C., Keen, J. H. & Davis, A. E. (1989) Proc. Natl Acad. Sci. USA 84, 8805-8809]. Alignment of 187 residues from the 40-kDa beta 1 C-terminal fragment revealed differences in 77 positions to the corresponding region of the beta 2 subunit and differences in 23 positions compared to the supposed beta 2-like protein. These findings suggest that the protein encoded by the rat cDNA clone AP105a is more closely related to the beta 1 subunit of the bovine adrenal Golgi adaptor protein 1 than to the beta 2 subunit of the rat plasma membrane adaptor protein 2. PMID- 8200351 TI - Copper-atom identification in the active and inactive forms of plasma-derived FVIII and recombinant FVIII-delta II. AB - The plasma-derived factor VIII (pd-FVIII) circulates as different heterodimers of heavy and light chains associated by a metallic ion still present in the functional activated factor VIII trimer of molecular mass 50,000-45,000-70,000 Da. The chelation of the metal leads to the dissociation of these complexes with a concomitant loss of the procoagulant activity. Until now, this ion has not been directly identified and its role in the structure/function relationships remains unclear. We report the first determination of the nature of this metal using atomic-absorption spectroscopy with Zeeman effect. A comparative identification was also performed with the new recombinant factor VIII, FVIII-delta II. In the different active pd-FVIII heterodimers (of molecular mass ranging over 210,000 80,000-90,000-80,000 Da) and in FVIII-delta II, copper was detected. This result is consistent with sequence similarities described between FVIII and copper binding proteins. The quantification of the copper content in FVIII-delta II and in the corresponding pd-FVIII dimer of 90,000-80,000 Da indicated, for both proteins, the presence of one copper ion/mol FVIII. Copper was also identified in the activated FVIII complex and remained in the dimer of 50,000-70,000 Da generated during FVIII inactivation. Further dissociation into isolated fragments of molecular masses 70,000 Da and 50,000 Da was concomitant with the loss of the copper ion. No copper was detected in the isolated fragment of molecular mass 45,000 Da. These results suggest that the presence of the cation is not directly related to FVIII activity but is an essential structural prerequisite for FVIII heavy-light-chain association. PMID- 8200352 TI - Assembly of functional skeletal muscle troponin complex in Escherichia coli. AB - The production of multi-subunit proteins of eukaryotic origin in Escherichia coli usually relies on the different subunits being expressed individually and the protein being reassembled in vitro. Here we describe the construction and characterization of plasmids capable of coexpressing the three subunits of chicken skeletal muscle troponin complex in E. coli. We demonstrate that the troponin subunits assembled in the cytoplasm of E. coli cell are fully functional. The troponin complex was purified to homogeneity in high yields. When reconstituted into actin filaments, the complex assembled in vivo was capable of regulating the myosin ATPase with a calcium dependence that was identical to the complex reconstituted in vitro. These results demonstrate that the coexpression of the subunits of a protein complex can prevent the accumulation of denatured proteins in inclusion granules. PMID- 8200353 TI - Procarboxypeptidase in rat pancreas. Overall characterization and comparison of the activation processes. AB - Three monomeric procarboxypeptidases and a binary complex consisting of a procarboxypeptidase and a chymotrypsinogen have been isolated from rat pancreas by HPLC. N-terminal sequence determination, substrate-specificity analysis and physico-chemical characterization showed that the carboxypeptidase precursors were the A1, A2 and B forms. No isomorphism could be detected for any of these proenzymes and no clear evidence was obtained for the presence of procarboxypeptidase-containing quaternary complexes of the types previously described for other species. Instead, we observed the presence of a binary complex between procarboxypeptidase A2 and chymotrypsinogen B. Among the major pancreatic endoproteinases, only trypsin was found to be a general activator of rat procarboxypeptidases in vitro. Time-course analysis of the products generated after trypsin addition confirmed that full activation of procarboxypeptidase A1 requires several cleavages in the C-terminal region (residues 87-94) of the activation segment, while procarboxypeptidases A2 and B require a single cleavage each. The carboxypeptidases released participate in the trimming of the activation segment in A1 and B, but not in A2, probably because of the high specificity of the latter in the active form. PMID- 8200354 TI - Mapping of Hsp70-binding sites on protein antigens. AB - Hsp70-binding sites were mapped on three antigens, the 16-, 19- and 38-kDa proteins of Mycobacterium tuberculosis, using overlapping synthetic peptides in a competitive-binding assay. In each protein, two or three prominent hsp70-binding sites were identified when peptides 20-amino-acid long were used, predominantly in regions containing clusters of aliphatic amino acids. Although there was an overall concordance in the pattern of peptide binding to hsp70 from bacterial (M. tuberculosis) and mammalian sources (immunoglobulin heavy-chain-binding protein), some differences in the specificity of polypeptide binding and the effect of peptides on ATPase activity were observed. PMID- 8200355 TI - No intermediate channelling in stepwise hydrolysis of fluorescein di-beta-D galactoside by beta-galactosidase. AB - For the hydrolysis of the two glycosidic bonds of fluorescein di-beta-D galactoside (FDG) by beta-galactosidase from Escherichia coli, small [Hofmann, J. & Sernetz, M. (1983) Anal. Biochem. 131, 180-186] to dramatic [Huang, Z. (1991) Biochemistry 30, 8535-8540] deviations from simple stepwise substrate intermediate-product kinetics have been reported. Intermediate channelling, a preferred hydrolysis of the intermediate fluorescein mono-beta-D-galactoside (FMG) formed from FDG at the active site and thus in a favourable position for further reaction, has been postulated. As there were reasons to doubt the previous findings and conclusions, the hydrolysis experiments have been repeated at initial FDG concentrations of 7-200 microM, following the concentrations of FDG, FMG and fluorescein with a reliable method, quantitative HPLC, to completion of the reaction. The transient appearance of substantial amounts of the intermediate FMG also in experiments with 200 microM FDG already rules out the existence of the most efficient intermediate channelling deduced by Huang (1991) from measurements of the initially developing fluorescence, incorrectly ascribed to fluorescein. Redetermination of the Michaelis constants for FDG and FMG led to much higher values than those reported previously. Fitting the progress curves by means of nonlinear regression combined with numerical integration of the rate equations resulted in good fits of the normal stepwise substrate-intermediate product mechanism, without any necessity of assuming a more complex course of the reaction. So one of the rare examples of the hydrolysis of two bonds at a single enzyme-substrate encounter has been invalidated. PMID- 8200356 TI - Hydrolysis of lactosylceramide by human galactosylceramidase and GM1-beta galactosidase in a detergent-free system and its stimulation by sphingolipid activator proteins, sap-B and sap-C. Activator proteins stimulate lactosylceramide hydrolysis. AB - Two exo-beta-galactosidases are involved in the lysosomal degradation of glycosphingolipids: GM1-beta-galactosidase (EC 3.2.1.23) and galactosylceramidase (EC 3.2.1.46). Analyses were performed with both enzymes, using lactosylceramides with varying acyl chain lengths as substrates that were inserted into unilamellar liposomes and naturally occurring sphingolipid activator proteins sap-B and sap C, rather than detergents, to stimulate the reaction. While sap-B was a better activator for the reaction catalyzed by GM1-beta-galactosidase, sap-C preferentially stimulated lactosylceramide hydrolysis by galactosylceramidase. The enzymic hydrolysis of liposome-integrated lactosylceramides was significantly dependent on the structure of the lipophilic aglycon moiety of the lactosylceramide decreasing with increasing length of its fatty acyl chain (C2 > C4 > C6 > C8 > C10 > C18). However, in the presence of detergents the degradation rates were independent of the acyl chain length. Hydrolysis of liposomal lactosylceramide was compared with sap-B-stimulated hydrolysis of liposomal ganglioside GM1 by GM1-beta-galactosidase and sap-C-stimulated degradation of liposomal galactosylceramide by galactosylceramidase. Kinetic and dilution experiments indicated that sap-B forms water-soluble complexes with both lactosylceramide and GM1. These complexes were recognized by GM1-beta galactosidase as optimal substrates in the same mode, as postulated for the hydrolysis of sulfatides by arylsulfatase A [Fischer, G. and Jatzkewitz, H. (1977) Biochim. Biophys. Acta 481, 561-572]. GM1-beta-galactosidase was more active on these complexes than on glycolipids (GM1 and lactosylceramides) still residing in liposomal membranes. On the other hand, dilution experiments indicated that degradation of galactosylceramide and lactosylceramide by galactosylceramidase proceeds almost exclusively on liposomal surfaces: both activators, sap-C and sap-B, stimulated the hydrolysis of lactosylceramide analogues with long acyl chains more than the hydrolysis of lactosylceramides with short acyl chains. PMID- 8200357 TI - The functions and consensus motifs of nine types of peptide segments that form different types of nucleotide-binding sites. AB - From an analysis of current data on 16 protein structures with defined nucleotide binding sites consensus motifs were determined for the peptide segments that form such nucleotide-binding sites. This was done by using the actual residues shown to contact ligands in the different protein structures, plus an additional 50 sequences for various kinases. Three peptide segments are commonly required to form the binding site for ATP or GTP. Binding motif Kinase-1a is found in almost all sequences examined, and functions in binding the phosphates of the ligand. Variant versions, comparable to Kinase-1a, are found in a subset of proteins and appear to be related to unique functions of those enzymes. Motif Kinase-2 contains the conserved aspartate that coordinates the metal ion on Mg-ATP. Motif Kinase-3 occurs in at least four versions, and functions in binding the purine base or the pentose. Two protein structures show ATP-binding at a separate regulatory site, formed by the motifs Regulatory-1 and Regulatory-2. Structures for adenylate kinase and guanylate kinase show three different sequence motifs that form the binding site for a nucleoside monophosphate (NMP). NMP-1 and NMP-2 bind to the pentose and phosphate of the bound ligand. NMP-1 is found in almost all the kinases that phosphorylate AMP, CMP, GMP, dTMP, or UMP. NMP-3a is found in kinases for AMP, GMP, and UMP, while NMP-3b binds only GMP. For the binding of NTPs, three distinct types of nucleotide-binding fold structures have been described. Each structure is associated with a particular function (e.g. transfer of the gamma-phosphate, or of the adenylate to an acceptor) and also with a particular spatial arrangement of the three Kinase segments evident in the linear sequence for the protein. PMID- 8200358 TI - Purification of rat liver plasma membrane glutathione transferase. AB - Glutathione transferases purified from plasma membrane and microsomal fractions from rat liver share similar enzymic properties. The activity of both proteins with 1-chloro-2,4-dinitrobenzene can be stimulated about 10-15-fold by N ethylmaleimide. No activation is observed using p-nitrobenzylchloride as a substrate. The enzymes are immunologically related as indicated by Western-blot analysis using antibodies against the microsomal glutathione transferase or against a synthetic peptide corresponding to the amino acid positions 55-64 of microsomal glutathione transferase. Isolated plasma membrane and microsomal glutathione transferases possess the same amino-terminal amino acid sequence and digestion with different proteases results in identical fragment patterns as displayed by SDS/PAGE. These data suggest that plasma membrane and microsomal glutathione transferase are identical proteins. PMID- 8200359 TI - Cell-specific expression and function of adenylyl cyclases in rat pituitary tumour cell lines. AB - The present study demonstrates cell-specific distribution and describes distinct functional regulation of different adenylyl cyclases (AC, types I-VI) in rat pituitary cell tumor cell lines (GH12C1, GH3 and GH4C1 cells) and pituitary tissue. Northern-blot analysis revealed a distinct pattern of cell-specific expression of the different AC types; Ca2+/calmodulin (CaM)-insensitive AC type II was found in all cell lines tested except GH(1)2C1 cells. The Ca(2+) inhibitable AC type VI was found in all cell types tested. We observed a lack of the Ca2+/CaM-sensitive AC type I in GH3 and GH4C1 cells. GH(1)2C1 cells exclusively contained both Ca2+/CaM-sensitive AC types I and III, the latter previously believed to be specific for olfactory tissue. An additional transcript of AC type III was found in rat brain and rat liver tissue. AC type IV, which is Ca2+/CaM insensitive, could be detected in the prolactin-producing GH3 and GH4C1 cells and pituitary tissue but not in growth-hormone-producing GH(1)2C1 cells. Basal and vasoactive-intestinal-peptide-(VIP)-releasing-hormone, somatostatin (SRIF) and thyrotropin-releasing-hormone (TRH)-modulation of AC activity was measured in the presence of 100 microM EGTA, anti-CaM serum (dilution 1:2000) or 10 microM trifluoroperazine. Antisera against guanine-nucleotide-binding protein (G-protein) alpha subunits (G(i)-2 alpha, Gs alpha) and beta subunits (G beta 35/36) and CaM were added for functional studies of the SRIF and VIP-modulated AC in GH(1)2C1 and GH3 cells. These experiments indicate that the VIP and the SRIF receptors are coupled to a Ca2+/CaM-sensitive AC in GH(1)2C1 cells, different from the AC involved in the regulation of cAMP levels in GH3 and GH4C1 cells. In addition, the beta gamma-complex is possibly able to modulate SRIF-inhibited AC activity by potentiating the inhibitory effect. The TRH receptor in GH3 and GH4C1 cells is coupled to a Ca2+/CaM-sensitive AC which is different from the already cloned forms of AC types I and III. We, therefore, conclude that hormone regulation of pituitary tumour cell functions differs between the GH cell lines, due to specific utilisation of AC types. PMID- 8200360 TI - Different types and different prognosis-study of 310 uterine sarcomas. AB - Three hundred and ten cases of uterine sarcomas, among them, according to pathology: LMS (Leiomyosarcoma)--117, MMS (Mixed mesodermal sarcoma)--62, ESS (Endometrial stromal sarcoma)--56, CS (Carcinosarcoma)--27, RBMS (Rhabdomyosarcoma)--18 and other sarcomas--30, were retrospectively evaluated at the Maria Sklodowska-Curie Memorial Cancer Center between 1950 and 1985. These mesodermal tumors were divided into uterine corpus sarcomas (295) and the rarely occurring uterine cervix sarcomas. As the main modality of treatment 307 patients underwent surgery. Almost all patients received adjuvant radiotherapy but 51 cases of LMS. Overall 5-year survival was 34.5% and in particular subgroups the survivals were as follows: the best, 52% in LMS; lower, 30% in ESS; poor survival about 20% in CS and MMS. In spite of low curability in the majority of subgroups except LMS, the cases of CS with primary site in uterine cervix distinguished itself with better results. No significant survival advantage was found for surgery plus radiotherapy in LMS with low grade mitotic activity, (10 mitoses/10 HPF) compared with surgery alone (63% and 54%). These cases seem to have better prognosis in LMS with high grade mitotic activity (10 mitoses/10 HPF) and do not require adjuvant radiotherapy. PMID- 8200361 TI - Natural killer cell activity in patients with ovarian tumors and uterine myomas. AB - Natural killer (NK) cells are considered to play a role in surveillance against neoplasia. Therefore, the aim of our study was to evaluate peripheral blood NK cell activity in patients with benign and malignant ovarian tumors as well as uterine myomas. NK cell activity was evaluated by means of 51/Cr-release cytotoxicity assay using K562 erythroleukemic cells as a target. We found that natural cytotoxicity of peripheral blood mononuclear cells was significantly (P > 0.01) decreased in patients suffering from both benign and malignant ovarian tumors as compared to healthy women. A degree of NK cell activity abrogation was higher in patients with malignant tumors. Similar decrease was also observed in patients with uterine myomas. Since ovarian tumors and uterine myomas are known to be associated with an increased serum levels of estrogens it is possible that abrogation of NK cell activity in these patients is related to immunosuppression mediated by these hormones. PMID- 8200362 TI - The management of granulosa-cell tumors of the ovary based on long-term follow up. AB - The results of treatment in 130 cases of GCT of the ovary treated in the Institute of Oncology in Warsaw and followed up from 5 to 40 years were analysed with respect to the methods of therapy and age of the patients. The highest 5 year survival rate (86%) was obtained by combination of radical surgery with external irradiation. Such treatment also resulted in the lowest percentage of early and late failures of the treatment (17%). Conservative surgery, applied in the Ist stage of GCT resulted in 69% of 5-year survivals and gave young women a chance of procreation; however, the majority (69%) of patients who underwent this treatment sooner or later developed a recurrence leading, in consequence, to death. PMID- 8200363 TI - Usefulness of determination of CA-125 in monitoring patients with ovarian carcinoma. AB - CA-125 was determined in 298 patients with ovarian carcinoma both initially, and during and after treatment. The upper limit of normal for CA-125 in our laboratory is 65 units/ml. Postoperatively, serum CA-125 antigen showed three distinct patterns: 20% of patients in whom levels fluctuate within the normal range have active disease; 100% of patients with fluctuations above 65 U/ml are found to have active disease; 100% of patients in whom levels of CA-125 increase progressively from any nadir, have active disease. An elevated concentration of CA-125 antigen indicates presence of tumor and allows avoidance of 2nd-look surgery. Serum CA-125 antigen fluctuating within the normal range does not indicate eradication of the viable tumor cells. PMID- 8200364 TI - History of 400 years of struggle against cancer in Poland. AB - The over 400-year history of struggle against cancer in Poland is presented in this work, from its beginning, marked by the establishment of the first hospital for cancer patients in Warsaw in 1592, up to the achievement of the main aim of the National Cancer Programme, i.e., the recent construction of a large modern cancer centre in Warsaw. In the meantime, a number of significant events have taken place in Poland for example, studies on cancer conducted in the 17th-19th centuries, a report on cancer mortality data which was published in 1888, and the Warsaw Committee on Cancer Research and Control, established in 1906. As regards the 20th century, the National Cancer Research and Control programmes were carried out (in 1924, 1952 and 1975), among other activities. An oncological network was built up in Poland based on 11 comprehensive cancer control centres and provincial outpatient clinics. At present, out of each 100,000 new cancer cases more than 70,000 die every year in Poland. The leading localizations in males are: lung (30.5%), stomach (9.8%), larynx (5.5%), prostate (5.1%) and urinary bladder (5.0%); in females: breast (17.5%), cervix uteri (9.8%), lung (6.6%), stomach (6.2%) and ovary (6.2%). Cancer patients' estimated probability of surviving 5 years is 26.4% (males) and 39.8% (females). PMID- 8200365 TI - Evaluation of selected prognostic factors in ovarian cancer. AB - Among the group of 367 women with ovarian cancer, 11 prognostic factors were examined. Eight of the factors had an important prognostic value regarding the longterm (5 and 10 years) survivals of ovarian cancer patients. There were the following significant prognostic factors: histological type, the degree of differentiation of the tumour, clinical stage, ascites, overgrowth of the capsule, or infiltration of the ovary surface, irregular shape of the tumour, cancer in both ovaries, and solid type of the tumour. The best prognosis was obtained for patients with mucous type of cancer (53.3%-5 and 26.7%-10 years survival). The poorest prognosis was obtained for the group of patients with undifferentiated cancers, respectively, 11.8 and 3.6%. PMID- 8200366 TI - Chemotherapy combined with surgery in the treatment of gestational trophoblastic disease (GTD). AB - Surgery combined with chemotherapy was applied in 34 out of 178 patients (19.1%) with GTD during treatment at the Institute of Oncology in Warsaw in the years 1977-1989. This mode of treatment was used twice as often in patients with MTD (Metastatic Tumour Disease) (31.6%) than in those with NMTD (Non Metastatic Tumour Disease) (14.2%). All 34 patients, who were operated on, had hysterectomy and 3 of them thoracotomy also. The most common indication for surgery was the chemoresistance of the disease, which had been stated in 53% of all treated surgically. All the patients with NMTD and those with good prognosis MTD, treated by combination of chemotherapy and surgery were cured, which confirms the efficacy of adjuvant surgery in these groups of patients. The role of surgery in patients with high-risk MTD is limited because of disseminated disease, frequently seen in this group. PMID- 8200367 TI - Combination of thermographic and ultrasound methods for the diagnosis of female breast cancer. AB - The experiment leads to the formulation of a non-invasive and highly efficient method for the detection of the female breast cancer. The proposed method is a combination of the results of ultrasound and thermography tests of the breast. The study is expected to produce the principles of test results analysis offering a 90% success rate in detecting breast cancer. PMID- 8200368 TI - The influence of tamoxifen on plasma coagulation and serous fibrinolysis. AB - Selected parameters of coagulation and fibrinolysis were determined in 25 postmenopausal women, treated chronically for breast cancer with the use of tamoxifen. The significant influence of tamoxifen therapy on the serous fibrinolysis parameters was found. The time of euglobulin lysis was shorter, the concentration of alpha 2-antiplasmin decreased, and plasminogen concentration increased. The content of antithrombin III, fibrinogen, and caolin-cephalin time did not change significantly during therapy, except the prothrombin rate which increased. Tamoxifen is an important medicine with beneficial influence on the fibrinolytic system, without affecting the serous coagulation system. PMID- 8200369 TI - Changes in the incidence and survivals of ovarian cancer in Poland. AB - The incidence and mortality trends, as well as survivals, are presented according to the Warsaw Cancer Registry data concerning 4,112 ovarian cancer cases registered in the years 1963-1988, in two populations, the urban of Warsaw City and the rural of the Warsaw Rural Areas (WRA). The standardized incidence rate in Warsaw in 1988 was 13.44/100,000 and it has not changed significantly in relation to the 1963 figure, but statistical significance characterized the increase of incidence in WRA population and the general population of Poland. The standardized incidence rates were as follows: WRA 1963 6.8, 1988 11.7; in Poland as a whole respectively, 6.5 in 1960 and 11.7 in 1988. The most rapid increase of incidence occurred in the 1960s, then the trend stabilized, and another increase began in 1984. The incidence growth was accompanied by similar trends in mortality. The mortality rates in 1988 were: 8.3 in Warsaw; 6.9 in Poland, and 6.9 in WRA. The mortality increase was statistically significant in WRA and in the total population of Poland. The analysis of mortality and incidence trends in Warsaw City and in Poland as a whole justifies the identification of Warsaw as a high-risk population, while Poland appears to be a population of rapidly growing ovarian cancer risk. Despite a statistically insignificant growth of ovarian cancer incidence and mortality in Warsaw, the risk keeps increasing as can be seen in the permanent increase of incidence and mortality rates which began in 1973, in increasingly age-specific incidence and mortality rates in almost all age groups, and in a shift of top incidence and mortality rates towards younger age groups. The risk of this cancer is higher in Warsaw City than in rural areas, but the urban/rural ratio was declining from 2.5 to 1.3 during the study period. The relative 5 years survival rates in Warsaw are similar to those observed world wide, and they are 37.3% against 38.5% in WRA. Compared with the previous period between the years 1963 and 1968, there has been an improvement in the 5-year survival rates in both populations and in all age groups, except the oldest, resident in Warsaw. PMID- 8200370 TI - Striking differences in the epidemiological picture of breast cancer in urban and rural areas in Poland. AB - Poland is a European country of medium female breast cancer risk but a steady, mean incidence growth of 3.5% per year makes this cancer the most frequent malignancy and a leading cause of cancer-related deaths among the women of the 1980s. Our analysis is based on data collected by the Warsaw Cancer Registry in the years 1963-1987. The crude incidence rate in Poland doubled against 1963 and was nearly 40/100,000 in 1988. In 1988 eight thousand women developed breast cancer. In Poland, the incidence of 37.7 was higher in Warsaw than the rate of 16.6 obtained for Warsaw Rural Areas (WRA) in 1963. The trend continued until 1988 to reach 59.7 and 33.5 in the respective areas. Incidence rapidly grew with age, starting in the group of 30 to reach its peak of 149.2 at 65 and over in Warsaw and 86.6 in WRA. Mortality rates in Warsaw grew from 16.6 in 1963 to 30.7 in 1988 and, from 10.8 to 17.4 in WRA in the respective years. The urban/rural ratio declined from 1.7 to 1.5 during this period. The unfavourable proportion (patient distribution according to clinical staging in Warsaw was: 0 + I-17.2%; II-34.1%; III-29.1%; IV-23.6%. The relative 5-year survivals in Warsaw were 58.7% and they improved little compared to the former periods. These figures were even lower in WRA and they showed a downward trend for women aged over 65. A steady increase in breast cancer risk observed after 1963 and the large proportion of advanced breast cancers diagnosed, were followed by poor results of treatment causing about 5,000 breast cancer deaths in Poland annually. PMID- 8200371 TI - Epidemiology of cancer in Poland. AB - Poland is a Central European country with the population of over 38 million. Its system of cancer control is organized in a three-level oncological network. The number of cancer cases diagnosed each year is about 100,000 and over 70,000 die of cancer every year. Every 4th inhabitant of Poland will contract cancer, every 5th dies from it. Poland is a country of medium cancer incidence rate (men: 252.2 per 100,000 population, women: 208.0 per 100,000). The yearly incidence growth is 1.99% in men and 0.64 in women. The leading cancer sites in Polish men are: lung, stomach, larynx, prostate, urinary bladder, and large bowel; in women: breast, uterine cervix, stomach, lung, and large bowel. Mean 5-year survival is 26.4%. PMID- 8200372 TI - Celebration of 60th anniversary of the Maria Sklodowska-Curie Institute of Oncology of Warsaw. PMID- 8200373 TI - Gynaecological oncology in Poland. AB - The control of gynaecological cancers in Poland has developed from three factors: 1) the organization of the Committee for Cancer Research and Control in 1906, which considered these activities as extremely important; 2) the personal commitment of Maria Sklodowska-Curie, and 3) the opportunity to train Polish physicians at the Foundation Curie in Paris after 1921, enhanced by the support of Head of the Fondation Professor Claude Regaud in introducing the "Paris Method" as a therapy against cervical cancer, to be provided for patients at the Radium Institute in Warsaw. The separation of gynaecological oncology as an independent branch of oncology occurred in Poland in 1951 when the Gynaecological Oncology Departments were opened first at the Institute of Oncology and later in other oncological clinics. The establishment of the Polish Gynaecological Society in 1992 was the next milestone. PMID- 8200374 TI - Epidemiology of breast and gynaecological cancers in Poland. AB - The epidemiological data on breast cancer and cancer of the female reproductive organs are presented in the light of data provided by the National Cancer Registry and the Warsaw Cancer Registry. Estimates say that cancer of the breast and the reproductive organs attacked 19,764 women in Poland, 1989, of whom 9,436 died. This number represents 41.2% of the total cancer incidence in women. The standardized incidence rates calculated for these cancers per 100,000 and arranged according to localization, were as follows: breast 34.4; cervix 19.5; ovary 12.4; corpus uteri 10.6. Mortality: breast 15.5; cervix 8.0; ovary 6.8; corpus uteri 2.5. Comparing with the average rates in EC countries, the risk in Poland of breast cancer was lower but was higher in cervical and uterine cancers. The risk of ovarian cancer was similar in Poland and the E.C. The relative 5-year survivals estimated for the years 1978-1982 in Poland were as follows: breast 49.3%; cervix 50.7%; and corpus uteri 66.1%, which was lower than in Switzerland, Finland, Australia, and USA (Caucasians); and similar in patients with ovarian cancer (35.1%). Particularly unfavourable 5-year survival rates were given for cancer of the breast and cervix in the rural areas. Unfavourable trends are observed in the control of the breast and cervical cancer in Poland which confirms inadequacy of the existing preventive programmes based on screening. According to estimates, the introduction of preventive measures could reduce cervical cancer mortality by 60% during 10 years and breast cancer mortality by 40% within 7 years, which means saving about 3,000 lives yearly. PMID- 8200375 TI - A long-term evaluation of the CIN-lesions. A clinicopathological study. AB - Among patients treated over a 20-year period cytological screening demonstrated a high-grade cervical dyscariosis (III-V Papanicolaou group) in 565 (2.3%) cases. In a group of 159 of these patients, all with cervical erythroplasia, a detailed study was possible and punch-biopsy (without colposcopy) was performed. Comparative analysis of cytology and pre-operative histology revealed good correlation. The patients in whom punch-biopsy demonstrated high-grade CIN and also those with negative histology, but with dyscariosis permanently occurring in cervicovaginal smears, underwent surgical treatment (conization). The results of histology in the punch-biopsies and in the surgical specimens of the cervix were discordant, mostly in low-grade CIN. Most patients are alive and well and remain in permanent clinical control. Conclusion--Cytology is a useful method of selecting the high-risk patients, who should subsequently be followed clinically, by cytology and histology. Surgical treatment seems to prevent invasive cancer: however these patients should remain under permanent control. PMID- 8200376 TI - Epidemiological evaluation of the efficiency of treatment of pre-invasive cervical cancer in Warsaw, 1969-1988. AB - An analysis of 2,281 cases of pre-invasive cervical cancer registered in Warsaw Cancer Registry during the years 1969-1988, showed that the rate of cervical cancers detected at the pre-invasive stage declined from 46.8% in 1970, to 26.8% in 1988. New cases of this cancer were diagnosed mainly in the age group up to 49 years of age (86.1%). Conservative treatment was applied relatively rarely (in 43.0% of cases) while the uterus with adnexes were removed fairly frequently (26.0%). The results of treatment were good (100.0% of 5-year survivals.). The 5 year survivals seem not to differ in relation to any particular treatment method used. PMID- 8200377 TI - An attempt, based upon 231 cases, to optimize clinical procedures in patients with preinvasive carcinoma of the cervix treated surgically. AB - The aim of study was an attempt to create models for patients with diagnosed preinvasive cervical carcinoma treated surgically in whom dysplasia, normal epithelium or invasive carcinoma may be predicted pre-operatively with given probability. Data obtained from the study material comprising 231 patients showed that the results were not sufficient to create an optimized model for the treatment of pre-invasive cervical cancer. The conclusion of the study is that pre-operative diagnostics must be extended. PMID- 8200378 TI - Clinical value of transvaginal, sonographically guided fine needle aspiration biopsy of parametria in recurrent cervical carcinoma. AB - Forty four patients with a clinically suspected relapse of cervical carcinoma were evaluated with transvaginal sonographically guided fine-needle aspiration biopsy (FNAB) of parametria in the Gynaecological Department of the Institute of Oncology, Warsaw, Poland. Sonographical scans and FNAB results were compared with subsequent clinical course (41 cases) and surgery (3 cases). Of the total of 56 aspiration biopsies 50 specimens were of cytological value. Overall diagnostic accuracy of FNAB was 82%, specificity and positive predictive value 100%, sensitivity 61% and negative predictive value 75%. As regards sonography the accuracy rate was 77%, the sensitivity as well as negative predictive value were 100%, specificity was 62% with false positive rate 23%. The definitive diagnosis of recurrence was obtained by FNAB in 13 out of 18 cases and in 8 of these radiotherapy was instituted. The negative FNAB correctly rules out the recurrent disease in 22 of 26 cases. In all cases with relapse parametrial lesions were detected on ultrasound scans. The Authors have found that sonographically guided FNAB of parametria is a useful diagnostic tool in imaging and biopsying of parametrial masses. As the conjunction of two complementary diagnostic methods this technique is an excellent tool for obtaining the cytologic verification of recurrence, especially in doubtful cases, when post-therapeutic pelvic fibrosis is present. It is also a quick, safe technique, well accepted by the patient. PMID- 8200379 TI - Evaluation of the hormonal function and features of the ultrasound picture of transposed ovary in cervical cancer patients after surgery and pelvic irradiation. AB - Conventional surgical methods for treatment of invasive cervical cancer inevitably lead to castration. In young women premature cessation of ovarian function may lead to serious short term and long term complications. The preservation of ovarian function if possible is crucial to improving quality of life. 48 patients with Ia and Ib carcinoma of the cervix entered this study. All patients were treated by Wertheim's radical hysterectomy with ovarian transposition. Some of them had adjuvant radiotherapy. It appears that radical surgery even with postoperative brachytherapy has not had adverse effect on ovarian function. It has been found that depletion of ovarian function might be expected in patients treated by external beam irradiation if the distance between the upper margin of the inlet field and the transposed ovary was less than 3 cm. In 91% cases, in USG examinations distinct reduction of transposed ovary echostructure were found. PMID- 8200380 TI - Screening for cervical cancer in Poland. AB - Despite the growing number of PAP tests performed in Poland every year, (approximately 3 million per year in 1992) the mortality rates of cervical cancer are stable or increasing. With the intention of changing this unfavourable situation, a team of specialists in 1988 has developed a model for cervical cancer screening in Poland. Six experimental centres were chosen for the implementation of this model. The principles of the screening system were as follows: 1) population-based; 2) individual invitations; 3) computer assisted; 4) reproducible; 5) cytotechnicians' participation; 6) target population 30-60 years; 7) frequency of PAP tests: every 3 years. Preliminary data from the population of 25,841 which was covered by the screening campaign in Warsaw showed a 70.1% attendance rate and detectability of 3 cases per 1,000 screened women. PMID- 8200381 TI - The value of transvaginal ultrasonography (TVS) in the assessment of myometrial and cervical invasion in corpus uterine neoplasma. AB - 62 women with histologically proven corpus uteri neoplasia were examined to estimate accuracy, sensitivity and specificity of TVS in assessing myometrial invasion and cervical involvement of the disease. Incorrect ultrasound interpretation were found in 9 cases (14.5%). Accuracy rate was 88.7% in myometrial infiltration and 93.5% in cervical invasion. The sensitivity of TVS in detecting the level of myometrial invasion was 96% and in cervical spread was the same. The specificity of this method in proper estimation the myometrial infiltration was 91% and in cervical involvement 95%. Concomitant myomas and primary radiotherapy may increase difficulties in determining the spread of neoplasia. All these facts have convinced us that TVS is of great value in gyneacological oncologic practice and deserves even wider application. PMID- 8200382 TI - Attempt at classification of hysteroscopic pictures of corpus uteri carcinoma. AB - When comparing types of hysteroscopic pictures--"cauliflower" fatty and multifocal--with prognostic features whose importance is already known (clinical advance, histological maturity, size of uterus, number of cses cured, and number of distant metastases). I have found that "cauliflower" and fatty types are diagnosed in patients with good prognostic features because they appear more often at I degree of advance and at highly matured carcinoma (G1). The survival rates are the highest--93% and 87%. The changes I have described as multifocal appeared in patients with high degree of advance of disease (III--78% I--21%) and with low matured carcinoma. The survival rate was much lower--74% and distant metastasis more frequent (15%) than in other groups of patients. So the pictures of the multifocal infiltrates have the most negative prognostic factors. Such diagnosis obliges to choose particularly precise, conscientious method of therapy and hysterography can be very useful to it. The problem which requires further investigations is the relatively high frequency of detectability of the multifocal changes on hysteroscopic pictures. It may be assumed that some additional, still unexplained features must exist in this form which, might possibly limit the frequency of diagnosis of hysteroscopic pictures with negative prognostic factors. PMID- 8200383 TI - Adjuvant progestagen therapy improves survival in patients with endometrial cancer after hysterectomy. Results of one-institutional prospective clinical trial. AB - A prospective study was conducted to determine the effectiveness of adjuvant hormonotherapy in endometrial cancer after surgery. Two hundred and five patients were randomly assigned to adjuvant progestagen treatment or were given no additional therapy. The follow-up was 5-years. We concluded that there was evidence of gain from adjuvant progestagen therapy in postoperative endometrial cancer. The group of patients who received progestagens had significantly longer survival than the control group without hormonotherapy (Logrank test; P < 0.001). PMID- 8200384 TI - Imaging brain infarcts by single-photon emission tomography with new tracers. PMID- 8200385 TI - Tumour-like thallium-201 accumulation in brain infarcts, an unexpected finding on single-photon emission tomography. AB - Thallium-201 brain single-photon emission tomography (201Tl-SPET) is widely used to detect viable tumour tissue with increased metabolic activity. When reperfusion takes place early in cerebrovascular lesions of embolic origin, the presence of tissue areas with increased regional blood flow and preserved metabolic activity can also be assumed. In the present study our purpose was to investigate whether or not foci of 201Tl accumulation occur in reperfused areas with sustained morphological integrity indicated by computed tomography (CT) scans not showing hypodensity in the acute or subacute period. In 16 stroke patients with possible cortical embolic infarction, dual 201Tl and technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) SPET was performed in both the acute and the subacute period. 99mTc-HMPAO SPET was performed to detect reperfusion. Follow-up CT scans from the same period were also available. In five cases 99mTc-HMPAO SPET ruled out reperfusion and 201Tl SPET was also negative. In four cases 99mTc-HMPAO studies indicated reperfusion early in the acute phase (24 72 h), and comparative CT, without showing hypodensity in the acute or subacute period, also favoured the possibility of sustained metabolic activity. In these cases 201Tl SPET was negative in both the acute and the subacute period. In seven cases CT already showed necrosis in 99mTc-HMPAO hypoperfused areas in the acute period, with negative results on corresponding 201Tl SPET. Later reperfusion occurred in the subacute period (8-14 days) as indicated by 99mTc-HMPAO SPET, at which time an unexpected focal accumulation of 201Tl was detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200386 TI - Dual-isotope autoradiographic measurement of regional blood flow and benzodiazepine receptor availability following unilateral middle cerebral artery occlusion. AB - Single-photon emission tomography (SPET) imaging in patients with complex partial epilepsy has shown that the seizure focus is characterized by both decreased interictal blood flow and decreased uptake of the benzodiazepine (BZ) receptor tracer iodine-123 iomazenil. The purpose of this study was to examine the confounding effect of decreased flow on iomazenil uptake. The left middle cerebral artery of four rats was occluded, and the animals were simultaneously injected with 25 microCi of iodine-125 iomazenil and 500 microCi of the blood flow tracer [123I]iofetamine (N-isopropyl-p-iodoamphetamine). All rats, including two sham, were sacrificed 1 h after injection, a time when uptake of both agents is nearly maximal. Control experiments showed that arterial occlusion for 1 h did not affect the total number of BZ binding sites. Using a dual autoradiographic technique, the uptake of both [123I]iofetamine and [125I]iomazenil was measured in more than 200 regions showing variable levels of reduced flow and expressed as a percentage of the contralateral homotypic area. The straight line fit of % [125I]iomazenil (y axis) versus % [123I]iofetamine (x axis) in all 200 regions had a slope of 0.74. Insofar as the rat is an accurate model of human subjects with epilepsy, these studies suggest that decreased flow to the epileptogenic focus will linearly exacerbate the decrease in uptake secondary to neuropathologic loss of BZ receptors. Thus, for localization of seizure focus, a single SPET image of [123I]iomazenil in an epileptic patient may have greater sensitivity than a comparable blood flow image, because the former is enhanced by both decreased flow and a loss of BZ receptors. PMID- 8200387 TI - The relationship between Helicobacter pylori-associated gastritis or ulcer disease and gastric emptying. AB - Forty-five patients with Helicobacter pylori (HP)-associated gastritis or ulcer disease were included in this study. Radionuclide-labelled solid meals were used to calculate gastric emptying times (GETs) and carbon-14 urea breath tests (14C UBTs) were used to measure the HP colonies quantitatively. The patients were assessed according to the following two criteria: (a) the HP colony number (i.e. high or low) and (b) the recorded duration of the GET (i.e. long or short). There was no statistically significant difference in the incidence of abnormal GET between high and low 14C UBT patients or in the incidence of abnormal 14C UBT between long and short GET cases. In conclusion, no significant relationship between HP-associated gastritis or ulcer disease and GET was found in this study. PMID- 8200388 TI - Dual-isotope myocardial imaging: feasibility, advantages and limitations. Preliminary report on 231 consecutive patients. AB - Two hundred and thirty-one patients underwent dual-isotope myocardial imaging (rest thallium-201 followed by stress technetium-99m sestamibi). The feasibility of the procedure was excellent: camera scheduling flexibility was improved and the duration of the procedure was less than that of a classical stress redistribution procedure. Interpretation of defects due to image attenuation was facilitated by the different attenuation properties of 201Tl and 99mTc-sestamibi in 11 of 19 patients. 201Tl cross-over on 99mTc was found to be 15% +/- 3% with doses of 201Tl and 99mTc-sestamibi of 3 and 10 mCi, respectively, and 7% +/- 2% with doses of 3 and 20 mCi. This protocol should preferentially be reserved for patients with a history of myocardial infarction and/or a basal left ventricular dysfunction, in whom assessment of myocardial viability is of major interest. Extensive clinical validation of the dual-isotope procedure is required and optimal acquisition and reconstruction parameters should be established. PMID- 8200389 TI - Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies. AB - Red marrow is usually the dose-limiting organ during radioimmunotherapy. Several non-invasive approaches to calculate the red marrow dose have been proposed. We compared four approaches to analyse the differences in calculated red marrow doses. The data were obtained from immunoscintigraphy of two antibodies with different red marrow kinetics [iodine-131-16.88 IgM and indium-111-OV-TL-3 F(ab')2]. The approaches are based on, respectively, homogeneously distributed activity in the body, a red marrow-blood activity concentration ratio of 0.3, scintigraphic quantification, and a combination of the second and third approaches. This fourth approach may be more adequate because of its independence from the chosen antibody. In addition, the influence of activity accumulation in liver, kidneys or cancellous bone on red marrow dose was studied. The calculated red marrow dose varied between 0.14 and 0.42 mGy/MBq for 111In-OV-TL-3 and between 0.13 and 0.68 mGy/MBq for 131I-16.88. If the radiopharmaceutical shows high affinity for cancellous bone or another organ situated near the red marrow, the activity in these organs must be included in dose calculations. This study shows a large variation in calculated red marrow dose and selection of the definitive non-invasive approach awaits validation. PMID- 8200390 TI - How good is technetium-99m mercaptoacetyltriglycine indirect cystography? AB - The aim of the present study was to estimate the sensitivity of indirect radionuclide cystography (IRC) performed with technetium-99m mercaptoacetyl triglycine (MAG3), in comparison with the micturition cystourethrography (MCUG) and direct radionuclide cystography (DRC), for the diagnosis of vesicoureteric reflux. Two groups of patients were selected: group I comprised 40 children who underwent IRC during the acute phase of urinary tract infection and an MCUG 6 weeks later; group II comprised 42 (other) children with known reflux, who underwent IRC and DRC during follow-up. Taking as the reference the total number of refluxing kidneys detected by means of any cystographic technique, 99mTc-MAG3 ICR missed two-thirds of the refluxing kidneys. Most of the small refluxes were missed, but so too were 50% of the major refluxes. Taking as the reference 99mTc dimercaptosuccinic acid (DMSA) scintigraphy, MCUG detected 91% of the patients with DMSA abnormalities on at least one kidney, DRC detected 95%, and IRC detected 46% and 43% respectively, in groups I and II. The use of 99mTc-MAG3 IRC as the sole technique for the detection of vesicoureteric reflux gives rise to an unacceptable number of false-negative results. PMID- 8200391 TI - A simple method for measuring glucose utilization of insulin-sensitive tissues by using the brain as a reference. AB - A simple method, without measurement of the plasma input function, to obtain semiquantitative values of glucose utilization in tissues other than the brain with radioactive deoxyglucose is reported. The brain, in which glucose utilization is essentially insensitive to plasma glucose and insulin concentrations, was used as an internal reference. The effects of graded doses of oral glucose loading (0.5, 1 and 2 mg/g body weight) on insulin-sensitive tissues (heart, muscle and fat tissue) were studied in the rat. By using the brain reference method, dose-dependent increases in glucose utilization were clearly shown in all the insulin-sensitive tissues examined. The method seems to be of value for measurement of glucose utilization using radioactive deoxyglucose and positron emission tomography in the heart or other insulin-sensitive tissues, especially during glucose loading. PMID- 8200392 TI - The renal transplant perfusion index: reduction in the error and variability. AB - For 15 years, perfusion indices derived from scintigraphic studies have proved useful in the serial evaluation of renal transplants and they have recently been confirmed as being more sensitive than Doppler ultrasound as an indicator of vascular rejection and cyclosporin toxicity. In the calculation of these indices, correction for administered activity is often accomplished using activity measurements made over a convenient artery which, therefore, has a critical influence on the value of the index obtained. In this communication, a theoretical assessment is made of the error and variability introduced into the calculation of the perfusion index, because of inadequate spatial sampling of activity in these narrow arteries and the consequential inconsistencies in the measurement of the arterial tracer activity. Using numerical simulation, it is shown that the errors in repeat studies on the same patient may be as high as 39% and between patients as high as 53%. These figures can be reduced to below 18% and 21%, respectively, by constructing a region of interest (ROI) to extend over as much of the arterial width as possible rather than relying only on the maximum pixel count. Further reduction to below 12% and 10% is possible by utilising a 128 x 128 acquisition matrix instead of 64 x 64 and drawing the ROI over the aorta instead of the iliac artery. PMID- 8200394 TI - Non-matched images with 123I-IMP and 99mTc-bicisate single-photon emission tomography in the demonstration of focal hyperaemia during the subacute phase of an ischaemic stroke. AB - Focal hyperaemia is a fairly common phenomenon in the subacute phase of an ischaemic stroke. This has rarely been reported with iodine-123 iodoamphetamine (IMP) and has never been identified using technetium-99m bicisate (99mTc-ECD). In this report, we present the case of a patient suffering from a left cerebral posterior stroke. 123I-IMP single-photon emission tomography (SPET) images showed a large area of significantly increased IMP activity located in the left occipital region whereas 99mTc-bicisate SPET displayed hypoactivity in the same area. PMID- 8200393 TI - Magnetic resonance imaging or metaiodobenzylguanidine scintigraphy for the demonstration of paragangliomas? Correlations and disparities. AB - Paragangliomas are tumours arising from paraganglionic tissue dispersed from the base of the skull to the pelvic diaphragm. These tumours produce symptoms by secreting catecholamines (functioning tumours) or by local tumour expansion. They can be part of several hereditary disorders. The introduction of magnetic resonance (MR) imaging and metaiodobenzylguanidine (MIBG) scintigraphy has provided new insights into paragangliomas and has tremendously changed the topographic diagnosis of paragangliomas. Both techniques have proven to be adequate in localising paragangliomas. In this report, the performance of these two noninvasive imaging methods in the examination of paragangliomas is compared and the merits and deficits of the two techniques are discussed. Both techniques produce comparable results in the detection of functioning paragangliomas. MR imaging, however, also demonstrates tumours that do not take up MIBG. MR imaging does not involve the use of ionising radiation and is not hampered by medication. Moreover, MR imaging has a higher spatial resolution. Because of these merits it is concluded that for demonstration of paragangliomas, whole-body MR imaging is the preferred and initial method of investigation. MIBG scintigraphy, on the other hand, continues to be a reliable method for non-invasive detection of functioning paragangliomas. At present it is clearly faster in whole-body imaging than MRI and it is definitely patient-friendly (no claustrophobia). It could be reserved for cases where a strong suspicion of a functioning paraganglioma persists, despite normal MR imaging findings, and for cases where doubt exists about the functional activity of one or more multicentric tumours. MIBG scintigraphy must be used in the evaluation of patients referred for iodine-131 MIBG treatment. PMID- 8200395 TI - Reversible findings of methylene diphosphonate bone scintigraphy in Raynaud's phenomenon: case report and review of the literature. AB - A 53-year-old woman with carcinoma of the right breast, spinal metastases and right arm lymphoedema was referred for bone scintigraphy prior to commencement of chemotherapy. The patient arrived in the department complaining of pain in the left hand, which appeared red and slightly swollen. Bone scintigraphy revealed increased tracer uptake in the first four metacarpal and all the carpal bones of the left hand. A repeat three-phase bone scintigram, performed 1 week later when the patient was asymptomatic, showed equal blood flow to both hands with normal blood pool and uptake in bone images. The case demonstrates a state of reversibly increased bone uptake in a patient injected at the time of an episode of Raynaud's phenomenon and the possible implications for scan interpretation. PMID- 8200396 TI - Technetium-99m diethylene triamine pentaacetic acid for intrathecal administration: are we playing with fire? PMID- 8200397 TI - The diagnosis of renovascular hypertension: the role of captopril renal scintigraphy and related issues. PMID- 8200398 TI - Gene therapy in urological oncology: principles, strategies and potential. PMID- 8200399 TI - Management of renal angiomyolipoma: a report of 14 cases and review of the literature. Is nonsurgical treatment adequate for this tumor? AB - 14 patients with renal angiomyolipoma are presented. Two of them had tuberous sclerosis (TS) with synchronous bilateral and multiple tumors. Two other patients without TS also had multiple tumors in 1 kidney. More than half the patients were symptomatic (n = 8), 2 of them with spontaneous rupture of the tumor. Misdiagnosis, spontaneous rupture and tumor growth can be prevented by utilizing conservative, organ-sparing techniques. In cases of solitary kidneys with large and/or hemorrhagic angiomyolipoma, superselective arterial embolization is indicated. PMID- 8200400 TI - Laparoscopic pelvic lymph node dissection for staging of prostatic cancer. AB - Assessment of the pelvic lymph node status is a major concern in prostatic cancer staging. In spite of a normal abdominopelvic CT scan examination in patients with organ-confined disease, 7-30% will have lymph node metastases at pathological examination and will not benefit from radical prostatectomy. Laparoscopy enables pelvic lymph node dissection via a minimally invasive approach. Twenty-nine patients underwent laparoscopic pelvic lymph node dissection (LPLND) for prostatic cancer staging. The average duration of the bilateral dissection was 90 +/- 40 min (range 35-180 min). One patient died of a stroke on postoperative day 1, without local complication. The peroperative complications were 1 injury of the external iliac vein, 1 ileal injury, 1 ureteral injury, all 3 (11%) requiring immediate or delayed laparotomy. One patient had a self-resolving bilateral obturator nerve paresis. A previously irradiated patient had perineal lymphedema for 4 weeks. The average number of lymph nodes removed was 8.4 +/- 3.4 (range 4 17) for bilateral LPLND. Five patients had lymph node metastases. The median length of stay for patients undergoing LPLND as a single procedure was 2 days (range 2-11 days). After an operational period, during which the complication rate was relatively high, we now consider LPLND as a safe and effective procedure for the staging of patients with organ-confined prostatic cancer, but considering the increased risk of complications during the application period, we do not encourage the generalization of this technique which should remain restricted to some particular strategies, as in combination with perineal radical prostatectomy. PMID- 8200401 TI - Preservation of antegrade ejaculation in retroperitoneal lymphadenectomy due to residual masses after primary chemotherapy for testicular carcinoma. AB - We report 18 consecutive patients with testis cancer and retroperitoneal residual masses with normal tumor markers, who underwent lymphadenectomy. Aiming to preserve the antegrade ejaculation, we carried out surgical modifications which basically attempt to preserve: (1) both sympathetic lumbar trunks, (2) the superior hypogastric plexus and (3) some of the postganglionic branches. With a mean follow-up of 28.1 months (range 6-62 months), 15 (83.3%) of the 18 patients preserved ejaculation, without significant differences between ejaculation volumes before and after lymphadenectomy. At the present time, 3 of 4 possible patients have fathered children. Mass size seems to be an important predictive factor of ejaculation preservation. One patient relapsed in the retroperitoneal dissection area, representing a recurrence rate of 5.5%. The disease-free survival rate was 94.4%, and 1 patient died due to disease progression with lung recurrence. Thus preservation of ejaculation was possible in most of these patients. PMID- 8200402 TI - Validity of kidney-preserving surgery for localized renal cell carcinoma. AB - A study was performed to evaluate whether kidney-preserving surgery would be appropriate or not, and in the affirmative for which indications. Eighty-one kidneys removed at Seoul National University Hospital between January 1987 and June 1991 were serially cut into 5-mm slices to probe for any small renal lesions. Of the 81 kidneys, 15 (18.5%) renal units contained 39 satellite nodules with histological patterns identical to the primary tumor. The number of satellite nodules was 2.6 per kidney (range 1-6). The size of the satellite nodules ranged from 0.5 to 2 cm (mean 0.9 cm). The presence of satellite nodules increased with increasing T stage and size of the primary tumor (p < 0.05 by Fisher's exact test). The presence of satellite nodules was significantly different between kidneys with primary tumors larger than 7 cm and less than 7 cm (p < 0.05 by the chi 2 test). Especially, no satellite nodules were found in 23 kidneys whose primary tumors were less than 5 cm. These observations suggest that kidney-preserving surgery could be a valuable treatment option for small localized renal cell carcinoma not only in patients with a single kidney or deteriorated contralateral kidney function but also in patients with normal contralateral kidneys, especially when the size of the tumor is less than 5 cm. PMID- 8200403 TI - Neoadjuvant chemotherapy for invasive bladder carcinoma: disease outcome and bladder preservation and relationship to local tumor response. AB - Thirty-nine patients with locally advanced transitional cell carcinoma of the bladder received presurgical combination chemotherapy in an effort to improve survival, reduce local tumor recurrence and distant failure, and enhance surgical resectability and potentially salvage the bladder. One to six cycles (median 2.8) of M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin), CMV (cisplatin, methotrexate, vinblastine), or VP16 CDDP (etoposide, cisplatin) were administered after initial diagnosis and clinical staging of the bladder cancer and transurethral resection of the tumor. Clinical staging was repeated before each cycle of chemotherapy. Transurethral resection and systemic neoadjuvant chemotherapy clinically downstaged 31 of 39 patients (79%). Subsequently, 26 patients underwent radical cystectomy and 13 patients received bladder salvage (6 received a partial surgical resection and 7 observation). At 41 months' median follow-up, 4-year overall survival was 63 +/- 17%, cancer-specific survival was 71 +/- 19%, local recurrence-free survival was 66 +/- 22%, and metastasis-free survival was 73 +/- 16%. Patients with a complete clinical and pathologic response had far better survival than those without a complete response; for pathologic stage, survival was 100% vs. 45% for those with residual tumor (p = 0.003). Local recurrence (Ta or TiS) occurred in 46% of those with their bladder salvaged and still in situ. These data suggest that with neoadjuvant chemotherapy bladder salvage seems feasible in selected patients, although they appear to be at higher risk for tumor recurrence. Accurate selection of the group of patients most likely to benefit is difficult and may not be possible in a predictable manner with currently available selection methods. PMID- 8200405 TI - Retrograde ejaculation and loss of emission: possibilities of conservative treatment. AB - Twenty-five patients with retrograde ejaculation/loss of emission were treated with ephedrine sulfate or imipramine hydrochloride. Seventeen of them suffering from both diabetes and retrograde ejaculation were treated with ephedrine or, in case that ephedrine failed to convert retrograde ejaculation into anterograde ejaculation, with imipramine. Positive results were obtained in 5/17 (29.3%) patients, i.e. in 3 (17.6%) and 2 (11.7%) patients on ephedrine and imipramine, respectively. The daily dose of ephedrine was 50 mg and that of imipramine 75 mg, during a 4-week period. In the group with retroperitoneal lymphadenectomy, after treatment with ephedrine, only 1 (12.5%) had retrograde ejaculation while the remaining patients (n = 7) continued to lack semen emission. These 7 patients were treated with imipramine, and 3 of them (42.8%) achieved anterograde ejaculation. In one third of patients with retroperitoneal lymphadenectomy and diabetes, with retrograde ejaculation or loss of semen emission, conservative treatment can offer improvement or conversion to anterograde ejaculation. PMID- 8200404 TI - Testicular tumor after cisplatin-based chemotherapy for germ cell malignancy. AB - Among 417 patients treated with cisplatin-based chemotherapy for germ cell malignancy (median follow-up 7 years) we observed 6 patients who developed a second tumor of the testis. In 3 cases the first tumor was of testicular origin, whereas in the other cases the initial tumor presented in the retroperitoneal space. Although cisplatin-based chemotherapy may reduce or delay the development of a contralateral testicular tumor, the risk apparently is not completely eliminated. Patients with primary retroperitoneal germ cell tumors need a close and careful follow-up, as they appear to be at an increased risk for developing a testicular tumor. PMID- 8200406 TI - Retroperitoneal laparoscopic nephrectomy and other procedures in the upper retroperitoneum using a balloon dissection technique. AB - This article describes a hydraulic balloon dissection technique. The retroperitoneum is developed via a small lumbodorsal incision between the edges of the musculus latissimus dorsi and musculus obliquus externus and then after visualization of its correct position the balloon catheter is filled with 500 1,200 ml of warm normal saline (according to patient size). The device consists of the finger of a surgeon's glove ligated around the end of a rigid bladder catheter. The balloon insufflation is maintained for 5 min to guarantee adequate hemostasis. Recently, we have replaced the balloon catheter by a balloon trocar sheath allowing direct endoscopic control of the hydraulic dissection. After retrieval of the balloon the CO2 insufflator is connected to the first trocar. All secondary trocars are placed under endoscopic control. The hydraulic dissection techniques also enable optimal creation of an effective pneumoperitoneum in children. Until now, we have used this technique for twelve procedures in the upper retroperitoneum including five nephrectomies, two nephroureterectomies, one tumor nephrectomy, one nephropexy, one renal cyst marsupialization and two renal biopsies. Up to now we have encountered no major complications. Three of the nephrectomized patients had undergone multiple previous abdominal surgical interventions. The retroperitoneal approach allows the surgeon to apply similar dissecting techniques as used in respective open procedures. It has become the routine approach for laparoscopic procedures in benign renal disease. This procedure can be performed even in cases with previous abdominal surgery. PMID- 8200407 TI - Laparoscopy-assisted radical nephrectomy without pneumoperitoneum. AB - A small renal cell carcinoma of the right kidney was completely removed from a 59 year-old women by laparoscopic radical nephrectomy without requiring a pneumoperitoneum. A 5-cm midline laparotomy incision was made and 3 small retractors were used for suspending the abdominal wall. Under laparoscopic observation, we safely positioned three trocars. The kidney was then removed en bloc together with the adrenal gland, perinephric fat and Gerota's fascia. The resected mass was enclosed in an entrapment sac and removed via the 5-cm abdominal incision without morcellation of the tissues. Three trocars could be positioned safely under direct observation and there were no adverse hemodynamic or ventilatory effects because the operation was performed without intraperitoneal carbon dioxide insufflation. There were no significant operative or postoperative complications. This procedure appears to be advantageous for the treatment of small renal cell carcinomas. PMID- 8200409 TI - Effects of balloon dilatation on canine ureteric physiology. AB - The concept of adynamic ureteric obstruction following balloon dilatation was explored in 12 female mongrel dogs. Upper ureteric segments were dilated to 15 french at 10 atm for 3 min. Pressure and motility in the dilated segments were compared to that proximal and distal to the dilated segment prior to, immediately after, and at 2 and 6 weeks after dilatation. Immediately after dilatation the dilated segment and proximal pelvi-ureter showed a rise in baseline pressure from 2.5 +/- 0.3 and 1.9 +/- 0.3 to 32 +/- 4.6 and 37.2 +/- 5.7 mm Hg, with an associated decrease in the amplitude of contractions. Distal ureteric pressure/motility was unaffected at this point. At 2 weeks, the motility of the pelvis, dilated segment and distal ureter was diminished. Nephrostograms showed hydronephrosis and dilated upper ureteric segments with extravasation in 2 animals. At 6 weeks there was residual dilatation but motility of the dilated segment, and that of the proximal pelvi-ureter and distal ureter had returned to normal. PMID- 8200408 TI - Antitumor effect of recombinant human tumor necrosis factor on human testicular tumors heterotransplanted in nude mice. AB - The antitumor effect of recombinant human tumor necrosis factor (rHu-TNF) on 2 human testicular tumors (embryonal carcinoma, TTSC-1, and teratocarcinoma, TTSC 4) heterotransplanted in nude mice was studied. Therapeutic antitumor effect was observed more evidently in TTSC-1 than TTSC-4 when more than 5 x 10(3) U/mouse of rHu-TNF was administered intratumorally. Complete tumor regression was observed in both TTSC-1 and TTSC-4 after intratumoral administration of rHu-TNF. Histological findings correlated well with the decrease in tumor volume of treated tumors. In contrast to these data, little antitumor effect was observed when the same dose of rHu-TNF was administered intravenously to nude mice bearing these tumors. In conclusion, intratumoral administration of rHu-TNF was a more effective and safe method than intravenous administration against human testicular tumors heterotransplanted in nude mice. PMID- 8200410 TI - Evidence for eosinophil activation in eosinophilic cystitis. AB - Eosinophilic cystitis (EC) is a rare condition. Recent studies have shown that activated eosinophils release cytotoxic cationic proteins which can induce tissue damage. Moreover, in vitro studies have shown that interleukin-5 (IL-5) is a cytokine able to attract and activate eosinophils. The goal of this study was to detect a possible activation of eosinophils in EC using electron microscopy, in situ hybridization with an IL-5 RNA probe and immunochemistry with a specific anti-IL-5 antibody. Using these combined methods in a typical case of EC, we found numerous activated eosinophils synthesizing and secreting IL-5 protein. IL 5 could enhance the activation of eosinophils and their cytotoxic potential in bladder tissues. This mechanism might explain the chronicity of the lesions in EC. PMID- 8200411 TI - Spontaneous rupture of a neobladder. AB - The spontaneous rupture of neobladder is an extremely rare entity of which there only exists one formerly reported case in the world literature. It is far more common after enterocystoplasty for augmentation (19 reported cases). We describe here the spontaneous rupture of a neobladder 8 months after performing cystectomy and bladder replacement by an enterocystoplasty in order to treat a bladder carcinoma. In this case the patient showed symptoms and signs of acute peritonitis. The diagnosis was carried out using a cystogram and the treatment consisted of a laparotomy with closure of the perforation and drainage of the peritoneal cavity. PMID- 8200412 TI - Postoperative pseudosarcomatous nodule: report of one case and review of the literature. AB - We present a case of a large postoperative pseudosarcomatous bladder tumour and review the literature for this exceptional benign tumour. Several lesions, especially leiomyosarcoma, must be discussed. Immunohistochemical studies are helpful. The evolution is always benign, even with an incomplete tumour ablation. PMID- 8200413 TI - Blockade of U50,488H analgesia by antisense oligodeoxynucleotides to a kappa opioid receptor. AB - The recently cloned kappa-opioid receptor has binding characteristics consistent with those of a kappa 1-opioid receptor. Repeated intrathecal administration of an antisense oligodeoxynucleotide against the kappa 1-opioid receptor selectively lowers U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)cyclohexyl]benzeneacetemide) analgesia (P < 0.02) without affecting mu or delta analgesia. A mismatched antisense oligodeoxynucleotide in which 4 bases had been switched is inactive against U50,488H analgesia. These studies confirm at the molecular level traditional pharmacological studies implying a distinct receptor mechanisms for kappa 1 analgesia and demonstrate the utility of antisense approaches in studies of opioid pharmacology. PMID- 8200414 TI - Involvement of glutamate receptors in the striatal enkephalin-induced dopamine release. AB - In anesthetized rats, the intrastriatal infusion of the delta-opioid receptor agonist, [D-Pen2,D-Pen5]enkephalin, increased the extracellular concentration of dopamine. This effect was abolished by the NMDA receptor antagonist, 3-[(+/-)-2 carboxypiperazine-4-yl]propyl-1-phosphonate, but was unchanged by the AMPA (D,L alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) and kainate receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione. This suggests that the dopamine release induced by the delta-opioid agonist depends critically on the involvement of glutamatergic transmission via NMDA receptors. PMID- 8200415 TI - Pharmacodynamics of tolfenamic acid in dogs. Evaluation of dose response relationships. AB - Tolfenamic acid was administered to beagle dogs at 2, 4 and 8 mg/kg bodyweight i.m. and the concentration of drug in plasma and in inflamed (administered carrageenan) and non-inflamed subcutaneous tissue cage fluid was measured. The concentration of thromboxane B2 in serum from blood allowed to clot under standardized conditions was determined and the concentrations of prostaglandin E2, 12-hydroxyeicosatetraenoic acid (12-HETE) and leucocyte numbers were measured in fluid from the carrageenan administered tissue cages. Skin temperature was also measured over each tissue cage following administration of drug. Tolfenamic acid displayed linear pharmacokinetics since the area under the plasma concentration time curve (AUC) values were 13.74 +/- 1.88, 29.82 +/- 6.53 and 50.52 +/- 5.73 micrograms/ml.h following administration of 2, 4 and 8 mg/kg, respectively. Tolfenamic acid proved to be a potent inhibitor of ex vivo thromboxane B2 generation in clotting blood. Maximal inhibition was greater than 80% at all dose rates and 97% at the 8 mg/kg dose rate 1 h after drug administration. It also proved to be a potent inhibitor of prostaglandin E2 production in inflammatory exudate, and significantly (P < 0.05) decreased prostaglandin E2 production at all dose levels. Tolfenamic acid did not significantly alter 12-HETE generation or white blood cell accumulation in inflammatory exudate. Tolfenamic acid significantly reduced the elevated skin temperature over carrageenan administered cages at all dose levels. PMID- 8200416 TI - Autoradiographic localization of dopamine D1-like receptors in the rabbit pulmonary circulation. AB - The pharmacological characteristics and the anatomical localization of dopamine D1-like receptors were studied in sections of rabbit lung using [3H]SCH 23390 as a ligand. [3H]SCH 23390 was bound to sections of rabbit lung in a manner consistent with the labelling of dopamine D1-like receptors. The binding was time , temperature-, and concentration-dependent belonging to a single class of high affinity sites. The dissociation constant value (Kd) was 2.05 nM, whereas the maximum density of binding sites (Bmax) averaged 85 +/- 4 fmol/mg tissue. The pharmacological profile of [3H]SCH 23390 binding to sections of rabbit lung is consistent with the labelling of dopamine D1 receptors. Light microscope autoradiography revealed the development of silver grains which correspond to [3H]SCH 23390 binding sites within the tunica intima and the tunica media of large intrapulmonary artery branches. The presence of silver grains was also observed in the tunica media, but not in the tunica intima of medium-sized pulmonary artery branches. No silver grains were observed in small-sized pulmonary artery branches or in the pulmonary veins. Dopamine D1-like receptors localized in the rabbit pulmonary circulation probably mediate vasodilatation. Further work is necessary to clarify the functional significance of the non homogeneous distribution of dopamine D1-like receptor sites in the pulmonary circulation. PMID- 8200417 TI - Ro 5-4864 has a negative inotropic effect on human atrial muscle strips that is not antagonized by PK 11195. AB - The effects of Ro 5-4864, a peripheral benzodiazepine receptor agonist (9 x 10( 6) M and 9 x 10(-5) M) and of PK 11195, a peripheral benzodiazepine receptor antagonist (3 x 10(-6) M and 3 x 10(-5) M), alone or together, on contraction parameters of human atrial muscle strips were studied. Atrial muscle strips were obtained from patients undergoing cardiac surgery. The strips were suspended in Krebs-Henseleit solution at 36.8 +/- 0.2 degrees C, connected to an isometric force transducer and then stimulated at 15 V above threshold and paced at 1.5 Hz. Ro 5-4864 at its higher concentration, alone or mixed with PK 11195 at both concentrations, depressed the contraction amplitude to 80% of the control value (P < 0.05). In conclusion, Ro 5-4864 had a small but significant depressant effect on the contraction amplitude of human atrial strips. Surprisingly, this effect was not reversed by the peripheral benzodiazepine receptor antagonist PK 11195. PMID- 8200418 TI - Measurement of central nervous system activity of systemically administered CCKB receptor antagonists by ex vivo binding. AB - In the present study we have described an ex vivo binding assay in mice to measure the central nervous system (CNS) activity of systemically administered CCKB receptor antagonists. This assay incorporated a transcardiac perfusion step to remove the residual blood from the brain, which otherwise may result in an overestimation of CNS activity. The benzodiazepine CCKB receptor antagonist L 365,260 had marked CNS activity in this assay following i.v. (ED50 12.0 mg/kg) and p.o. (ED50 20.0 mg/kg) administration, whereas the dipeptoid CCKB receptor antagonist, CI988 exhibited relatively weak CNS activity following i.v. injection (ED50 > 30.0 mg/kg). In contrast, following i.c.v. administration, CI988 potently inhibited ex vivo binding of [125I]Bolton Hunter-CCK-8S to mouse brain. The recently described acidic tetrazole CCKB receptor antagonist, L-368,935 had potent CNS activity with an ED50 of 5.6 mg/kg i.v. and an ED50 of 1.9 micrograms/kg i.c.v. These studies suggest that the weak CNS activity of CI988 following systemic injection may, in part, be due to poor brain penetration and that the ex vivo binding assay is a useful way of assessing the brain penetration of CCKB receptor antagonists. PMID- 8200419 TI - Nicotinic receptor binding of [3H]cytisine, [3H]nicotine and [3H]methylcarbamylcholine in rat brain. AB - Three radiolabeled nicotinic receptor agonists were examined for their binding characteristics and for inhibition by cholinergic compounds in order to distinguish possible differential affinities for subtypes of neuronal nicotinic acetylcholine receptors. KD and Bmax values for [3H]cytisine, [3H]methylcarbamylcholine and [3H]nicotine were determined from Scatchard analysis using an enriched whole-brain membrane fraction from male Sprague-Dawley rats. Respective KD values were 0.15, 1.07 and 0.89 nM while Bmax values were 99, 64 and 115 fmol/mg protein respectively. All three ligands fit a one-site model of receptor-ligand interaction. Concentration-inhibition curves were used to determine Ki values for 16 cholinergic compounds. The rank order of potencies for displacement of the three ligands was: (-)-cytisine > (-)-nicotine > (-)-lobeline = methylcarbamylcholine > 1,1-dimethyl-4-phenylpiperazinium, (+)-nicotine, dihydro-beta-erythroidine, (+/-)-nornicotine > carbachol > arecoline >> oxotremorine, tetrahydroaminoacridine, AF102B >> (-)-cotinine > RS86 = heptylphysostigmine. Correlations of the affinities of these compounds determined with the three ligands were very near to unity. In contrast, there was a negative correlation of affinities for [3H]cytisine compared to affinities for the muscarinic receptor agonist, [3H]oxotremorine-M, and the muscarinic receptor antagonist, [3H]quinuclidinyl benzoate. Using membranes from whole rat brain yields data suggesting that all three nicotinic ligands bind to the same nicotinic acetylcholine receptor subtype, and are unable to distinguish subtypes of neuronal nicotinic acetylcholine receptor at the level examined. PMID- 8200420 TI - Intestinal effect of morphine 6-glucuronide: in vivo and in vitro characterization. AB - Morphine 6-glucuronide, a major metabolite of morphine with potent analgesic actions, is a potent inhibitor of intestinal motility when administered to rats by the intracerebroventricular (i.c.v.) route. Morphine 6-glucuronide was 62-fold more active than morphine in inhibiting gastrointestinal transit, whereas it was only 25-fold more potent in abolishing intestinal migrating myoelectric complexes. Pretreatment with naloxone (5 micrograms/rat i.c.v.) completely prevented the disappearance of migrating myoelectric complexes induced by the morphine metabolite. In contrast, in the guinea pig ileum bioassay, morphine 6 glucuronide and morphine inhibited the electrically evoked contractions of the tissue with similar potency, although in the guinea pig ileum binding assay the metabolite showed 4-fold lower affinity for the opiate receptor. The low naloxone Ke values against morphine 6-glucuronide or morphine indicated that the action of both drugs in guinea pig ileum was mediated by mu-opioid receptors. PMID- 8200421 TI - Pharmacological profile of selective muscarinic receptor antagonists on guinea pig ileal smooth muscle. AB - The present study examined the effects of a series of tricyclic muscarinic receptor antagonists on muscarinic receptors present in the guinea-pig ileum, both in vitro and in vivo. The selectivity profiles of these antagonists and that of atropine were determined by their affinity for cortical muscarinic M1, cardiac M2 and submandibular M3 receptors and for m4 receptors expressed in CHO cells. The compounds pirenzepine, UH-AH 37, AQ-RA 391 and AQ-RA 618 possessed high affinity (pKi 7.94-8.22) for muscarinic M1 receptors. Pirenzepine exhibited the most pronounced muscarinic M1 selectivity. AF-DX 384 and AQ-RA 741 possessed an approximately 10-fold higher affinity for the cardiac muscarinic M2 receptor than AF-DX 116. However, both compounds also exhibited high affinity for muscarinic m4 receptors. High affinity for muscarinic M3 and m4 receptors was observed for UH AH 37, AQ-RA 391 and AQ-RA 681. The antagonists were then tested for their interaction with the muscarinic receptors which are responsible for the methacholine-induced contraction of longitudinal muscle in vitro, circular muscle in vivo and muscarinic receptors which mediate the distension-evoked ascending reflex contraction of circular muscle in vitro. Compounds showing high affinity for muscarinic M3 receptors (e.g. AQ-RA 618) were the most potent antagonists in the functional experiments. Comparison of the binding displacement data with the functional results indicates that the effects of methacholine on the longitudinal and circular muscle of the guinea-pig ileum were predominantly mediated by muscarinic M3-type receptors. In contrast, the correlation between muscarinic M2 receptor affinity and antagonism of muscarinic receptors in the ileum was very weak. PMID- 8200422 TI - Assessment of physical dependence after continuous perfusion into the rat jugular vein of the mixed inhibitor of enkephalin-degrading enzymes, RB 101. AB - We investigated if continuous activation of opioid receptors by their endogenous ligands could lead to the development of physical dependence. Catheters were implanted for chronic i.v. drug administration in rats and connected to an infusion pump. On the fifth day of perfusion, the severity of naloxone (5 mg/kg s.c.)-precipitated withdrawal was evaluated. Large behavioral changes and body weight losses were observed in rats chronically treated with morphine (0.17 mg/120 microliters/h). In contrast, only one withdrawal symptom (tremor) was significant in rats treated with the mixed inhibitor of enkephalin-degrading enzymes, RB 101 (1.20 mg/120 microliters/h). Morphine and RB 101 were perfused at doses which give same analgesic responses 6 h after the start of perfusion. This lack of physical dependence after drastic conditions of administration emphasizes the potential clinical interest of systemically active mixed inhibitors as new analgesics. PMID- 8200423 TI - SR 48692 inhibits neurotensin-induced [3H]dopamine release in rat striatal slices and mesencephalic cultures. AB - In rat striatal slices, the increase (114 +/- 11%) in K(+)-evoked [3H]dopamine release induced by neurotensin (10 nM) was antagonized by 2-[(1-(7-chloro-4 quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol-3-yl) carboxylamino]tricyclo(3.3.1.1.3.7)decan-2-carboxylic acid (SR 48692, IC50 = 1.2 +/- 0.11 nM). SR 48692 (100 nM) also suppressed the neurotensin (10 nM)-induced increase (47%) in K(+)-evoked [3H]dopamine release in primary cultures of fetal rat mesencephalic cells. These results further characterize SR 48692 as a potent antagonist of neurotensin receptors in the rat. PMID- 8200424 TI - Antitussive effect of [Met5]enkephalin-Arg6-Phe7 in mice. AB - We examined the effect of [Met5]enkephalin-Arg6-Phe7 (MEAP) on the capsaicin induced cough reflex in mice. Intracerebroventricular administration of MEAP significantly decreased the number of coughs in a dose-dependent manner. The antitussive effect of MEAP was blocked by nor-binaltorphimine, a selective kappa opioid receptor antagonist. However, beta-funaltrexamine, a mu-opioid receptor antagonist, had no effect on the antitussive effect of MEAP. On the other hand, the antinociceptive effect of MEAP, as determined in the tail-flick test, was blocked by both nor-binaltorphimine and beta-funaltrexamine. Naltrindole, a delta opioid receptor antagonist, had no effect on either the antitussive effect or the antinociceptive effect of MEAP. These data suggest that MEAP exerts its antitussive effect in mice through the stimulation of kappa-opioid receptors, whereas the antinociceptive effect of MEAP is mediated through the simulation of both kappa- and mu-opioid receptors. PMID- 8200425 TI - Buspirone enhances head twitch behavior in mice. AB - We studied the effects of buspirone, a 5-HT1A receptor agonist, on head twitch behavior induced by 5-hydroxy-L-tryptophan (5-HTP) administered together with pargyline in mice. Buspirone dose dependently (0.1-10 mg/kg i.p.) enhanced head twitch behavior. This effect was blocked by (-)-propranolol and NAN-190 (1-(2 methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine hydrobromide). The enhancing effect of buspirone was also observed when mice were pretreated with p chlorophenylalanine. These findings suggest that the enhancing effect of buspirone on head twitch behavior may be exerted through the activation of post synaptic 5-HT1A receptors. PMID- 8200427 TI - Effect of activation of 5-HT1A receptors at the ventral medulla on phrenic nerve activity. AB - The purpose of this study was to determine the effects of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (8-OH-DPAT), on respiratory activity (phrenic nerve activity) following application to the ventral medullary surface in the cat. In addition, in order to determine if the action of 8-OH-DPAT was localized to structures at the ventral medulla, we examined the distribution of [3H]8-OH-DPAT to other brain regions and to the peripheral circulation. 8-OH-DPAT (0.0625-8 micrograms) produced a dose-related increase in respiratory rate when applied at either the intermediate or caudal areas on the ventral surface of the medulla. The maximal change in respiratory rate was 9 +/- 2 and 8 +/- 1 breaths/min at the intermediate and caudal areas, respectively. Integrated phrenic nerve amplitude was not significantly affected at these sites except at the 8 micrograms dose where it was decreased. No change in phrenic nerve activity was observed with 8-OH-DPAT application at the rostral area. [3H]8-OH-DPAT was not found to distribute to other brain regions or to the peripheral circulation following application to the ventral medullary surface. The results of this study suggest that 8-OH-DPAT causes changes in respiratory activity, primarily respiratory rate, by acting on neuronal structures at the ventral surface of the medulla. PMID- 8200426 TI - Dopamine D1 receptors are involved in the ACTH-induced reversal of hemorrhagic shock. AB - In an experimental model of volume-controlled hemorrhagic shock causing the death of all rats within 30 min, the intravenous (i.v.) bolus injection of the adrenocorticotropic hormone fragment 1-24 (ACTH-(1-24)) (160 micrograms/kg) induced a prompt and sustained improvement of cardiovascular and respiratory function, with 100% survival 2 h after treatment. Pretreatment with either haloperidol, 300 micrograms/kg i.v. (antagonist at dopamine D1 and D2 receptors), or (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepin-7-ol hemimaleate (SCH 23390), 50 micrograms/kg intraperitoneally (selective antagonist at dopamine D1 receptors), significantly inhibited the effect of ACTH-(1-24). A complete inhibition was produced by intracerebroventricular pretreatment with SCH 23390 (0.1 micrograms/rat). On the other hand, both i.v. and i.c.v. pretreatment with l-sulpiride (selective antagonist at dopamine D2 receptors) (25 mg/kg and 80 micrograms/rat, respectively) had only minor effects. These data suggest that the mechanism of the ACTH-induced reversal of hemorrhagic shock involves the activation of dopamine D1 receptors in the brain. PMID- 8200428 TI - Differential laminin gene expression in dorsal root ganglion neurons and nonneuronal cells. AB - Laminin is a substrate for cell migration and process outgrowth during development and may play an important role in peripheral nerve regeneration. While most studies have emphasized the expression and production of this glycoprotein by Schwann cells, in the current study we use in situ hybridization to examine the expression of the various laminin chain genes in neuronal as well as nonneuronal cells of normal adult rat lumbar dorsal root ganglia. Hybridization using cRNA probes derived from cDNAs encoding nonhomologous regions of each laminin chain showed differential localization of the chain messages within the ganglia. B2 chain mRNA was abundant in large and small neurons, satellite cells, and Schwann cells. B1 chain message was also localized in satellite and Schwann cells, but its neuronal expression was primarily restricted to a subpopulation of smaller neurons. Message encoding merosin M chain, an A chain variant, was localized within satellite cells and Schwann cells but was absent or of very low abundance in neurons. A chain mRNA was not detectable in any of the three nervous tissue cell types. The differential expression of the four laminin chains in the DRG is discussed in relation to the functional epitopes of the molecule. PMID- 8200429 TI - Synaptic 5'-nucleotidase activity reflects lesion-induced sprouting within the adult rat dentate gyrus. AB - In development, the ectoenzyme 5'-nucleotidase marks maturing cerebellar and cortical synapses, but it is localized in glial cells in the normal, adult nervous system. With a histochemical lead technique, we have now investigated its localization during reactive synaptogenesis in the dentate gyrus of adult rats deprived of entorhinal afferents. A band of enhanced 5'-nucleotidase reaction product was present in the outer portions of the dentate molecular layer between 5 and 75 days after destruction of the ipsilateral entorhinal cortex. At the ultrastructural level, 5'-nucleotidase-positive microglia and degenerating axon terminals were numerous within this band during the first postoperative week. Between Days 7 and 75, intact synapses were found that exhibited 5'-nucleotidase reaction product in their clefts. Astrocytic labeling was abundant. No enzyme positive synapses and few labeled glial elements were present in the control molecular layer. Conspicuous 5'-nucleotidase activity within synaptic clefts of mossy fiber terminals was present between Postoperative Days 10 and 40 on the operated side, but the staining was sporadic on the control side. We conclude that 5'-nucleotidase is associated with lesion-induced synaptic remodeling in the dentate gyrus. The band of 5'-nucleotidase reaction product within the outer molecular layer corresponds to the zone where the lesioned entorhinal fibers degenerate and where other afferents sprout. Here, the transient appearance of 5' nucleotidase within synaptic clefts parallels the time course of synaptic reinnervation. The enzyme is also indicative of the sprouting response of mossy fiber terminals. Functional properties of 5'-nucleotidase in purinergic neuromodulation and cellular adhesion may be relevant for the generation and plasticity of synaptic contacts. PMID- 8200430 TI - Survival of fetal neocortical grafts implanted in brain infarcts of adult rats: the influence of postlesion time and age of donor tissue. AB - We have previously found that fetal cortex taken from 16- to 18-day-old donors survives grafting to the infarcted cortex 5-7 days after middle cerebral artery occlusion. The present study was undertaken to examine the effect on graft survival of varying the age of the fetal donor tissue and the time between vessel occlusion and graft implantation. First, a cell suspension of neocortical tissue was grafted from fetuses aged 15, 17, or 20 gestational days to the infarcted cortex of hypertensive rats which had undergone arterial occlusion 5-7 days earlier. There were no significant differences in the mean size or general morphology assessed in Nissl- and acetylcholinesterase-stained sections between the groups. Second, neocortical tissue was grafted from fetuses aged 15 gestational days to the infarcted cortex at different times following arterial occlusion. When surgery was delayed until 5-7 days, 3 weeks, or 8 weeks postocclusion, graft survival was significantly better than when implanted 1 day postocclusion. Implantation after 3 weeks yielded grafts that also were significantly larger than those in rats grafted 5-7 days after cortical infarction. The results indicate that there is no crucial upper donor age limit for dissociated fetal neocortical grafts in terms of graft survival and volume. Furthermore, a delay between lesion and transplantation is desirable in this stroke model. The host brain environment seems to be most hospitable around 3 weeks after arterial occlusion. PMID- 8200431 TI - Autonomic and sensory reinnervation of smooth muscle transplanted to the anterior chamber of the eye: effect of target postnatal age. AB - The ability of the nervous system to provide target innervation is greatest in early development, but decreases as a function of age. The objective of the present study was to determine if age-related changes occurring within the target tissue contribute to this decline. Periorbital tarsal smooth muscle from donor rats 6, 14, 30, and 48 days postnatal were transplanted to the anterior chamber of the eye of 84- to 90-day-old host rats. The tissue was removed at 3, 6, or 10 days post-transplant and immunostained for presumptive sympathetic nerves (dopamine beta-hydroxylase-immunoreactive, DBH-ir), sensory (calcitonin gene related peptide-immunoreactive, CGRP-ir) or parasympathetic (vasoactive intestinal polypeptide-immunoreactive, VIP-ir). DBH-ir sympathetic fibers sprouted into target from donors of all ages. However, the rate of ingrowth was most rapid in tissue from 6-day-old donors. In contrast, CGRP-ir sensory fibers showed no age-related differences, but grew more rapidly than sympathetic fibers. However, the innervation density at 10 days was comparable for both types of nerves. No significant VIP-ir parasympathetic ingrowth could be demonstrated at any age. We conclude that smooth muscle target in developing animals can have selective effects on different populations of ingrowing fibers; the rate of sympathetic ingrowth declines with maturity, whereas ingrowth of sensory fibers is not altered. PMID- 8200432 TI - Quantitative assessment of the effect of chronic phrenicotomy on the induction of the crossed phrenic phenomenon. AB - The present study was carried out to determine if chronic peripheral phrenicotomy has a functional influence on the plasticity that is normally demonstrated by phrenic motoneurons in the spinal cord following spinal cord injury. Young adult female Sprague-Dawley rats were divided into an experimental and a control group. Left intrathoracic phrenicotomies were carried out at 1, 2, 3, and 4 weeks prior to induction of the crossed phrenic phenomenon and crossed phrenic nerve activity recording in the experimental group. Control animals were not subjected to chronic phrenicotomy. In each animal the crossed phrenic phenomenon was induced by left C2 spinal cord hemisection and turning off the ventilator. The reflex induced activity in the phrenic nerve ipsilateral to hemisection is defined as "crossed phrenic nerve activity." All animals were subjected to spinal cord hemisection 24 h before crossed phrenic nerve activity recording. The results showed that there is a transient but statistically significant depression of crossed phrenic nerve activity at 2 weeks postphrenicotomy and a recovery to the normal activity level at 4 weeks postphrenicotomy. One control experiment was carried out to assess the effects of phrenicotomy on respiratory activity that is normally present in the phrenic nerve (i.e., not reflex-induced). This "primary respiratory nerve activity" is different from crossed phrenic nerve activity in that the phrenic motoneurons are driven by different bulbospinal respiratory pathways. The results indicated a marked decrease in primary respiratory nerve activity at 1 week after phrenicotomy with no significant recovery by the 4th week after phrenicotomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200433 TI - Analysis of neurulation in a mouse model for neural dysraphism. AB - Elongation of the neuraxis was analyzed quantitatively with respect to the subpopulation of longitudinally oriented mitoses in the neuroepithelium in homozygous embryos of the loop-tail (Lp) mutant mouse, which is characterized by failure of fusion of the neural folds from the midbrain to the tail, as well as a shortening of the neuraxis. Correlations were made with mitotic cell orientation in the underlying gut and notochord, which are likewise shortened. In the abnormal dysraphic embryos at the 7- to 11-somite stage, the percentage of longitudinally oriented mitotic spindles in the neuroepithelium was significantly less than in normal embryos. In contrast, significant differences were not obtained with respect to the orientation of mitotic spindles in the gut or notochord. At the 15- to 20-somite stage, significant differences in mitotic orientation in the neuroepithelium, gut, or notochord did not occur between dysraphic and normal embryos. The results suggest that during elevation and fusion of the neural folds, a decrease in the percentage of longitudinally arranged spindles in the neuroepithelium of Lp/Lp embryos may contribute to the disturbance in neuraxial elongation and possibly closure failure, but that the shortened gut and notochord that also characterize this mutant may not result from defective orientation of mitotic spindles. PMID- 8200434 TI - Relation of nimodipine dose and serum concentration to learning enhancement in aging rabbits. AB - Nimodipine, a 1,4-dihydropyridine calcium channel blocker, has been shown to enhance learning in aging rats, rabbits, and monkeys. Using an intravenous drug model, the relations among nimodipine dosage, nimodipine plasma concentration, and acquisition rate of the conditioned eyeblink response in aging rabbits were observed. Animals treated with nimodipine reached a behavioral criterion of 80% conditioned responses more quickly than did vehicle-treated control animals. Nimodipine doses produced marked behavioral effects, with statistically significant values starting at 0.5 micrograms/kg/min and reaching maximum efficacy at the minimal dose of 1 microgram/kg/min. Nimodipine at this dose exhibited an effect from the first day of infusion and facilitated learning rate threefold in comparison to control animals. Increasing the nimodipine dose to 3 and 5 micrograms/kg/min did not further facilitate learning rate. As nimodipine doses were augmented, the concentration of the nimodipine in plasma increased in a dose-related fashion. The most effective serum concentration for enhancing learning seemed to be distributed between 10 and 50 ng/ml. Concentrations above 50 ng/ml did not exert a more pronounced effect on the hippocampally dependent trace eyeblink conditioning task. The results of this study suggest that nimodipine may be useful in enhancing learning abilities in aging brain and have established the minimal serum concentration of nimodipine which must be achieved for this effect. PMID- 8200435 TI - Distribution of intracerebral ventricularly administered neurotrophins in rat brain and its correlation with trk receptor expression. AB - To assess the potential effectiveness by which injected neurotrophins can diffuse throughout the brain, we used autoradiographic and immunohistochemical techniques to examine the brain distributions of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) after a single injection into the lateral cerebral ventricle (ICV) in rats. As described previously, ICV injected NGF labeled cholinergic neurons in the basal forebrain. Injection of BDNF resulted in few or no labeled neurons in the basal forebrain or in the substantia nigra. However, very intense labeling was associated with the ventricular walls and immediate parenchyma. The distribution of NT-3 after ICV injection was intermediate between that of NGF and BDNF. In the basal forebrain, similar neurotrophin distributions were observed in neonate versus adult animals. Our in situ hybridization analysis has shown that mRNA encoding the BDNF receptor(s) (trkB) is highly expressed by ependymal cells as well as by many neurons and glia. On the other hand, expression of the high-affinity NGF receptor (trkA) is restricted to cholinergic neurons in basal forebrain and striatum. In addition, staining with antisera specific for the trkA or trkB receptors demonstrated that their expression patterns closely reflect their mRNA distributions. Taken together, these data suggest that the presence of the trkB receptor on the ependymal layer of the ventricle and its expression throughout the brain parenchyma represents a significant impediment to the adequate diffusion of ICV-injected BDNF into the brain for delivery to target neurons. PMID- 8200436 TI - Transsynaptic effect of an intrastriatal fetal nigral graft on the sensitivity of the substantia nigra pars reticulata to muscimol in the rat. AB - In the present study, we have investigated the effect of a unilateral 6 hydroxydopamine lesion of the nigrostriatal pathway and of a fetal nigral graft in the striatum on circling induced by unilateral microinjection of muscimol in a target structure of the striatum, the substantia nigra pars reticulata. A group of ovariectomized female rats received a unilateral nigral lesion with 6 hydroxydopamine. The lesioned animals were then tested for apomorphine circling (0.25 mg/kg sc). The animals which displayed circling with this drug were divided into two groups with equivalent circling rate. One group received a graft of 1.5 x 10(6) cells taken from the ventral mesencephalon of 14- to 15-day-old rat embryos and the other was kept as control. Six months after the graft, all animals received one microinjection on each side of the GABAergic agonist muscimol (25 ng/0.5 microliters) in site A (rostral part) or in site B (caudal part) of the substantia nigra pars reticulata using indwelling guide cannulae. Circling was monitored during 90 min after the injection. Our results show that: (1) Unilateral degeneration of the nigrostriatal pathway was associated with a decrease of contralateral rotation when muscimol was injected in site A (rostral part) and an increase when administrated in site B (caudal part) of the substantia nigra pars reticulata on the lesioned side compared to the intact side. (2) A fetal nigral graft implanted into the striatum can normalize the changes in GABAergic sensitivity in site A but not in site B of the substantia nigra pars reticulata. PMID- 8200437 TI - In brown Norway rats, MPP+ is accumulated in the nigrostriatal dopaminergic terminals but it is not neurotoxic: a model of natural resistance to MPTP toxicity. AB - Rats have been described as being insensitive to relatively high doses of systemically administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that in primates induces a neurological syndrome identical to idiopathic Parkinson's disease. The current explanation for the rat resistance is that most of the MPTP is converted into the toxic metabolite 1-methyl-4 phenylpyridium (MPP+) by the MAO-B present in the brain vessel endothelium. Since MPP+ is a polar compound, a very low amount could cross the blood-brain barrier and be present inside the brain. We administered C57 BL mice and Brown Norway rats with either MPTP (30 mg/kg, ip) or the combined treatment MPTP + diethyldithiocarbamate (DDC). In mice, DDC prolonged the striatal exposure to MPP+, potentiated the MPTP-induced acute syndrome, and enhanced the MPTP-induced striatal dopamine depletion. In rats, DDC potentiated the MPTP-induced acute syndrome, but no changes in the striatal dopamine were observed after either MPTP or DDC + MPTP administration. Also in rats, however, high doses of MPP+ were measured in the striatum of MPTP-alone treated rats and DDC delayed the MPP+ elimination from the striatum. When MPTP alone or DDC + MPTP was administered to rats unilaterally lesioned with 6-hydroxy dopamine (6-OH-DA), the levels of MPP+ measured in the intact striatum were significantly higher than those found in the 6-OH-DA-lesioned striatum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200438 TI - Basal ganglia GABAA and dopamine D1 binding site correlates of haloperidol induced oral dyskinesias in rat. AB - Chronic haloperidol treatment in the laboratory rat induces spontaneous orofacial movements in some but not all of the animals, a behavior which has been described in the literature as vacuous chewing movements (VCMs). In an attempt to understand the neurochemical mechanism of these rat dyskinesias, we measured regional dopamine D1, D2, and GABAA binding density in rats with and without VCMs after chronic haloperidol treatment and in untreated controls using in vitro receptor autoradiography and correlated the binding changes with the dyskinetic behavior. Chronic haloperidol treatment produced an overall increase in dopamine D2 family receptor binding in the caudate putamen and in nucleus accumbens in both groups of treated rats, those with and without VCMs. In the haloperidol treated rats with VCMs, a significant increase in GABAA receptor density occurred in the substantia nigra pars reticulata (SNR), with a trend in those rats without VCMs. However, only in those haloperidol-treated animals with VCMs did a significant decrease in dopamine D1 receptor density occur in SNR. These receptor alterations are consistent with a process of haloperidol-induced neuronal death of striatonigral fibers. However, we have failed to identify cellular evidence of such toxicity. Alternatively, the receptor changes may reflect increased dendritic dopamine release in SNR, or, more speculatively a functional response to chronically diminished striatonigral pathway activity. Perhaps the release of dopamine from dendrites of the local DA-containing neurons might be variably enhanced with ongoing haloperidol treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200439 TI - Characterization of photochemically induced spinal cord injury in the rat by light and electron microscopy. AB - This study characterized by light and electron microscopy 49 photochemically induced lesions in adult rat spinal cord at 16 time intervals from 2 days to 17 months after lesioning. Vascular thrombosis, resulting from an intravascular photochemical reaction induced by a rose bengal/laser beam interaction, led within a few days to an extensive area of tissue deterioration. This area, termed the "lesion cavity" in contrast to the "secondary cavity" observed later, was at least 6 mm long and, at the epicenter, extended across most of the spinal cord width and from the dorsal surface to a level near the central canal. The area of spared tissue, 43% of the spinal cord cross-section at 2 days, did not change significantly between 2 and 56 days. Large numbers of macrophages populated the degenerating area by 5 days. This necrotic area was surrounded by a thin peripheral rim of largely intact white matter dorsally and laterally except at the epicenter where the white matter degenerated dorsomedially. In these peripheral regions, demyelination and, by 14 days, remyelination by both oligodendrocytes and Schwann cells (SCs) were evident. By 28 days, far more SCs (and meningeal cells) had entered the dorsal spinal cord, typically at the epicenter where meningeal thickening was most striking, and had migrated farther into the lesion cavity. These SCs and the axons they myelinated remained prominent in dorsal regions for many months, particularly at the epicenter; the proportion of SC to oligodendrocyte myelin diminished away from the epicenter. By 8 weeks, the lesion cavity was considerably diminished in size and thereafter it contained scattered macrophages, SC-myelinated axons, and blood vessels, primarily medially owing to flattening into clefts bilaterally. The cavity was partly bordered by astrocytes whose surfaces toward the lesion cavity were highly irregular and coated with basal lamina. Bare axons, consistently seen by electron microscopy at 5 days to 6 months, were typically ensconced among astrocytes starting at 28 days. Also by this time large, smoothly contoured, empty secondary cavities appeared, usually rostral and caudal to the epicenter; they did not increase in size or number with time. From 28 days to 17 months postlesion they occurred in 68% of the lesioned spinal cords. The secondary cavity border was composed of cells thought to be astrocytes but, surprisingly, the luminal surface was smooth and lacked basal lamina, in contrast to the primary lesion cavity border. Thus, two types of cavities formed after photochemical lesioning. This lesioning technique may provide an appropriate milieu to better understand aspects of the vexing problem of post-traumatic syringomyelia in the human. PMID- 8200440 TI - Fertilization of Xenopus eggs imposes a complete translational arrest of mRNAs containing 3'UUAUUUAU elements. AB - The early embryonic development of Xenopus is mainly governed by post transcriptional regulations until the mid-blastula transition. In this report, we present evidence demonstrating that fertilization of Xenopus eggs triggers a complete translational arrest of mRNAs containing UA-rich elements in their 3' untranslated region. This control is maintained at least until the mid-blastula transition. Neither maturation nor pseudo-fertilization of the egg is sufficient for triggering this control, suggesting that components originating from the male gamete are involved in the mechanism. Moreover, this control is exerted whether the mRNA is polyadenylated or not. PMID- 8200441 TI - The covalent maleimidobenzoyl-actin-myosin head complex. Cross-linking of the 50 kDa heavy chain region to actin subdomain-2. AB - We have identified the region of actin involved in the covalent coupling of maleimidobenzoyl-G-actin to the central 50 kDa segment of the myosin-S-1 heavy chain by analyzing the structure of the maleimidobenzoyl-G-actin-S-1 conjugate using selective proteolytic digestions, amino acid sequence determinations and novel cross-linking reactions between S-1 and different maleimidobenzoyl-G-actin derivatives. The cross-linking is shown to occur only on the stretch of residues 48-67 in actin subdomain-2 with Lys-50, residing on the outer part of the DNase-I binding loop, as the most likely site of cross-linking. Because the maleimidobenzoyl-F-actin-S-1 complex undergoes the same coupling process, the data provide experimental evidence in favor of the recent model of the rigor F actin-S-1 complex suggesting a close contact between structural elements of the lower domain of the 50 kDa fragment and the top of actin subdomain-2. PMID- 8200442 TI - Spin trapping of nitric oxide produced in vivo in septic-shock mice. AB - A nitric oxide (.NO) spin-trapping technique combined with electron paramagnetic resonance (EPR) spectroscopy has been employed to measure the in vivo production of .NO in lipopolysaccharide (LPS)-treated mice. The in vivo spin-trapping of .NO was performed by injecting into mice a metal-chelator complex, consisting of N methyl-D-glucamine dithiocarbamate (MGD) and reduced iron (Fe2+), that binds to .NO and forms a stable, water-soluble [(MGD)2-Fe(2+)-NO] complex, and by monitoring continuously the in vivo formation of the latter complex using an S band EPR spectrometer. At 6 h after intravenous injection of LPS, a three-line EPR spectrum of the [(MGD)2-Fe(2+)-NO] complex, was observed in the blood circulation of the mouse tail; the [(MGD)2-Fe2+] complex was injected subcutaneously 2 h before EPR measurement. No signal was detected in control groups. Administration of NG-monomethyl-L-arginine, an .NO synthase inhibitor, caused a marked reduction in the in vivo EPR signal of the [(MGD)2-Fe(2+)-NO] complex, suggesting that the .NO detected is synthesized via the arginine-nitric oxide synthase pathway. The results presented here demonstrated, for the first time, the in vivo real time measurement of .NO in the blood circulation of conscious, LPS-treated animals. PMID- 8200443 TI - Refolding proteins by gel filtration chromatography. AB - We have developed a facile means for the refolding of milligram quantities of purified proteins that employs gel filtration chromatography. We demonstrate by electrophoretic mobility shift and NMR spectroscopy that human ETS-1 protein, bovine ribonuclease A and E. coli integration host factor can be refolded into the native conformation using this technique. We have extended this strategy to the preparation of milligram quantities of macromolecular complexes suitable for structural analysis by NMR spectroscopy or X-ray crystallography. The diverse challenges to overcome in refolding these proteins illustrates the potential of this technique as a general approach for recovery of recombinant proteins produced as insoluble inclusion bodies. PMID- 8200444 TI - Regulation of interleukin-6 receptor expression by interleukin-6 in human monocytes--a re-examination. AB - We have studied the expression and regulation of the interleukin-6 receptor (gp80) and its signal transducer gp130 in primary human blood monocytes. Here, we show that freshly isolated human monocytes express mRNAs for gp80 and gp130. In contrast to a previous report [(1989) FEBS Lett. 249, 27-30] we find that neither lipopolysaccharide nor interleukin-6 (IL-6) lead to a down-regulation of IL-6 receptor mRNA in monocytes. Also in the human monocytic cell line Mono Mac 6 no effect of IL-6 on receptor mRNA levels was observed. For signal transducer gp130 mRNA in monocytes a small and transient up-regulation by IL-6 was found. PMID- 8200446 TI - Cleavage of supercoiled double-stranded DNA by several ribosome-inactivating proteins in vitro. AB - Several ribosome-inactivating proteins (RIPs), such as ricin (including its A chain), luffin, cinnamomin and camphorin, were found to express enzymatic activity to cleave supercoiled double-stranded DNA. In particular, alpha-sarcin, a RIP with a novel ribonuclease activity, was first proved to have this activity. They convert supercoiled DNA into a nicked circular conformation at low concentrations and further into a linear form at high concentrations: they have no effect on linear DNA. Although intact type II RIPs exhibited no RNA N glucosidase activity, they were detected to cleave supercoiled DNA. Even if ricin A-chain was treated by boiling, its activity on supercoiled DNA was largely retained. PMID- 8200445 TI - A major cellular substrate for protein kinases, annexin II, is a DNA-binding protein. AB - We have screened a human cDNA expression library in lambda gt11 for clones encoding Alu-binding proteins using direct binding of labeled Alu DNA to recombinant phage lysates fixed on a membrane, and isolated a clone 98% identical in sequence to the well-known substrate of protein kinases, annexin II, which was suggested earlier to play a role in transduction of mitogenic signals and DNA replication. A diagnostic property of annexins is their binding to phospholipids in the presence of calcium ions, and we have found that the interaction of proteins of human nuclear extracts with Alu subsequences is suppressed by Ca/phosphatidylserine liposomes, suggesting overlapping of Ca/phospholipid- and DNA-binding domains in annexin II. PMID- 8200447 TI - Expression and functional characterisation of a synthetic version of the human D4 dopamine receptor in a stable human cell line. AB - A synthetic version of the human D4 (hD4) dopamine receptor was prepared. The G/C content of the natural gene was reduced by 14% without altering the amino acid composition of the corresponding protein sequence. HEK293 cells were transfected with the synthetic hD4 gene and stable clones resistant to G418 selected. The hD4 receptor expressed from the synthetic gene had identical pharmacological characteristics to the native hD4 receptor [(1991) Nature 350, 610-619; (1992) Nature 358, 149-152]. Functional studies with cells expressing the synthetic hD4 gene indicated negative coupling of this receptor to adenylate cyclase. PMID- 8200448 TI - Activity oscillations predicted for pyruvate dehydrogenase complexes. AB - A kinetic model for the pyruvate dehydrogenase complex is analyzed. The model takes into account intermediate channeling through the lipoyl network attached to the complex core, as well as inter-related regulatory effects of protein X acetylation and enzyme phosphorylation. The model predicts undamped oscillations of enzyme activity. PMID- 8200449 TI - Thermal stability of lipid-depleted purple membranes at neutral and low pH values. AB - Differential scanning calorimetry was used to compare the thermal behavior of native and delipidated purple membrane fragments at pH values corresponding to purple, blue and acid-purple forms. At neutral pH, delipidation results in a 2.5- to 3-times increase in the cooperativity of the denaturational transition, accompanied by a minor increase in its temperature. At pH values below 5 the delipidated membranes exhibit considerably higher thermal stability than the native membranes. The reversible predenaturational transition observed in the native state is not detectable upon delipidation. There is no strict correlation between color changes upon acidification and deionization of either native or delipidated purple membranes and their thermal stability. PMID- 8200450 TI - Light signals are transduced to the phosphorylation of 15 kDa proteins in Neurospora crassa. AB - A microsomal fraction prepared from the mycelia of the band (bd) strain of Neurospora crassa showed enhanced phosphorylation of two small proteins with molecular masses of around 15 kDa (ps15) by the irradiation of the reaction mixture containing [gamma-32P]ATP at 0 degrees C for 1 s with blue light (450 nm, 6 mumol/m2/s or 420 nm, 80 mumol/m2/s). The reaction was stopped at 5 s of incubation at 0 degrees C after blue light irradiation. The light effect could not be detected in ps15, when a microsomal fraction from a blind mutant, wc-1 or wc-2 was used. The mixing followed by homogenization of the microsomal fractions from wc-1 and wc-2 restored the activity to simulate the phosphorylation of ps15 by blue light. The phosphorylated amino acid residue of ps15 was unstable when the proteins on a nylon membrane were exposed to an acid or alkaline solution, suggesting that the phosphorylated residue was aspartic acid. The other phosphorylated protein with a molecular mass of 70 kDa (p70) showed no light effect in the phosphorylation and the phosphorylated residue was estimated to be histidine, since it was stable in alkaline solution. PMID- 8200451 TI - Temperature-dependent change of serological specificity of Candida albicans NIH A 207 cells cultured in yeast extract-added Sabouraud liquid medium: disappearance of surface antigenic factors 4, 5, and 6 at high temperature. AB - The cells of Candida albicans NIH A-207 strain (A-strain) cultivated in YSLM at high temperatures (37 and 40 degrees C) did not undergo agglutination with the factor sera 4, 5, and 6 in a commercially available factor serum kit, 'Candida Check', and formed a grape-like shape. The mannans isolated from the cells had lost their reactivity against the factor sera in ELISA. It was also revealed by 1H NMR analysis that the mannans contained neither a phosphate group nor a beta 1,2-linked mannopyranose unit, although these mannans increased the non-reducing terminal alpha-1,3-linked mannopyranose unit. The cells and the mannans prepared by cultivation at such high temperatures followed by 27 degrees C in the same medium entirely recovered the reactivity with the factor sera. PMID- 8200453 TI - Kinetics and equilibria of S-nitrosothiol-thiol exchange between glutathione, cysteine, penicillamines and serum albumin. AB - The kinetics and equilibria of S-nitrosothiol-thiol (SNO-SH) exchange reactions were determined using differential optical absorption. At pH 7.4 and 37 degrees C, k2 values ranged from 0.9 M-1.s-1 for the reaction between S-nitroso glutathione (GSNO) and N-acetyl-penicillamine, and up to 279 M-1.s-1 for the exchange between S-nitroso-penicillamine (penSNO) and GSH. SNO-SH exchange involving GSH/GSNO and cysteine/cySNO was relatively rapid, k2 approx. 80 M-1.s-1 with an equilibrium constant slightly in favour of GSNO. GSNO was strongly favoured in equilibrium with penSNO, keq 0.0039. In the case of SNO-SH exchange between S-nitroso human serum albumin (albSNO) and GSH or cysteine k2 values were 3.2 and 9.1 M-1.s-1, respectively. The results show that the initial rate of SNO SH exchange between physiological albSNO (7 microM) and venous plasma levels of GSH and cysteine is very slow, < 1%/min. On the other hand, if a nitrosothiol such as cySNO were to enter a cell, it would be rapidly converted to GSNO (43%/s). PMID- 8200452 TI - Post-transcriptional repression of thymidine kinase expression during cell cycle and growth stimulation. AB - In vertebrates, endogenous thymidine kinase (TK) gene expression is strictly growth-dependent. Here we report that in continuously cycling Ltk-mouse fibroblasts, stably transfected with a vector expressing human TK cDNA from a constitutive promoter, enzyme activity rises 8-fold at the G1/S phase transition and declines again in G2. The mechanism did not involve changes in protein stability. When hTK was put under the control of a hormone-inducible promoter, production of high mRNA levels following addition of dexamethasone did not result in any enzyme activity in resting NIH-3T3tk- cells. After growth stimulation with serum, TK activity rose together with the onset of DNA synthesis only in the simultaneous presence of the hormone. PMID- 8200454 TI - Isolation, primary structures and metal binding properties of neuronal growth inhibitory factor (GIF) from bovine and equine brain. AB - Human neuronal growth inhibitory factor (GIF) impairs the survival of cultured neurons and is deficient in the brains of Alzheimer's disease victims. We have isolated and sequenced analogous proteins from bovine and equine brain. By comparing their primary structures with those of human, mouse and rat GIFs, a consensus GIF sequence was obtained. Although this exhibits ca. 65% similarity with primary structures of mammalian metallothioneins (MTs), some significant differences are expected in the content of helix and turn secondary structures. In contrast to MTs, which usually bind 7 Zn(II) ions, human, bovine and equine GIFs contain 1-4 Cu(I) and 3-5 Zn(II) ions in species-specific ratios. The observed Cu(I) phosphorescence (lambda max, 550-590 nm; tau, 100 microseconds at 77 K) indicates the presence of the cuprous ion. Both bovine Cu1Cd5- and the equine Cu3Cd3-GIF derivatives (Cd replacing Zn) exhibit cadmium-dependent absorption and CD features between 220-260 nm characteristic of Cd-thiolate clusters similar to those in Cd-MTs. PMID- 8200455 TI - Antimycin inhibition of the cytochrome bd complex from Azotobacter vinelandii indicates the presence of a branched electron transfer pathway for the oxidation of ubiquinol. AB - Antimycin A and UHBDT inhibit the activity of the purified cytochrome bd complex from Azotobacter vinelandii. Inhibition of activity is non-competitive and antimycin A binding induces a shift to the red in the spectrum of a b-type haem. No inhibitory effects were seen with myxothiazol. Steady-state experiments indicate that the site of inhibition for antimycin A lies on the low-potential side of haem b558. In the presence of antimycin A at concentrations sufficient to inhibit respiration, some direct electron transfer from ubiquinol-1 to haem b595 and haem d still occurs. The results are consistent with a branched electron transfer pathway from ubiquinol to the oxygen reduction site. PMID- 8200456 TI - Picosecond absorbance difference spectra of the antenna of photosynthetic purple bacteria. The influence of exciton interactions and librations. AB - The influence of exciton interactions and pseudolocal librational modes on the relaxation of photo-induced absorption changes of the light-harvesting antenna of the photosynthetic purple bacterium, Rhodospirillum rubrum, was studied in the ps time domain. A hypothesis is put forward that the long-lived librational modes can occur in the circular aggregate of light-harvesting bacteriochlorophyll molecules of the core antenna. The model spectra obtained quantitatively fit the shape of the photo-induced picosecond absorbance difference spectra. The model predicts the decay of photo-induced spectra with the time constant within tens of picoseconds. PMID- 8200457 TI - Identification of a putative membrane-interacting domain of CTP:phosphocholine cytidylyltransferase from rat liver. AB - A putative membrane-interacting domain of CTP:phosphocholine cytidylyltransferase (CT) was identified using two peptide-specific antibodies. One antibody (SA2) was raised against the N-terminus of CT (amino acid residues 1-17) and the other antibody (SA209) against an alpha-helical domain of the enzyme (amino acid residues 247-257). Both antibodies quantitatively immunoprecipitated CT from rat liver cytosol and showed specificity towards CT when octylglucoside extracts of rat liver cytosol were assessed by Western blot analysis. However, further experiments revealed that the antibodies had different characteristics. Whereas the antibody directed against the N-terminus of CT (SA2) did not influence CT/membrane interaction, the new antibody (SA209) against the alpha-helical domain of the enzyme interfered with this interaction. Our results provide experimental evidence that the alpha-helical domain (amino acid residues 228-287) of CT may serve as a membrane-interacting domain. PMID- 8200458 TI - Phosphoinositides in membranes that build up the triads of rabbit skeletal muscle. AB - The total membrane concentrations of PtdIns, PtdIns4P, and PtdIns(4,5)P2 contribute to the functional capacity of the Ins(1,4,5)P3 signalling system which is operating in skeletal muscle but the function of which is still unknown. Total amounts of these phosphoinositides have been determined in purified membranes of transverse tubules (TT) and terminal cisternae (TC) of the sarcoplasmic reticulum (SR) of rabbit skeletal muscle. PtdIns and PtdIns4P have been detected in both membrane systems whereas PtdIns(4,5)P2 (290 mumol/mol phospholipid) is confined only to TT. A much greater pool of PtdIns(4,5)P2 seems, however, to be located in the sarcolemma away from the triadic junction. PMID- 8200459 TI - Interleukin 2 mediates p72syk activation in peripheral blood lymphocytes. AB - The ability of interleukin 2 (IL-2) to stimulate p72syk activity in intact porcine peripheral blood lymphocytes was examined. We demonstrated that IL-2 activated p72syk in a time- and dose-dependent manner, for which its peak time and maximum responsive dose were 5 min and 100 U/ml, respectively. This activation was observed only in cytosolic fractions and not in membrane ones. However, IL-2 failed to induced calcium mobilization. Moreover, IL-2-inducible p72synk activation was not affected when extra- intracellular calcium was depleted. These data suggest that the IL-2 signaling pathway through p72syk in peripheral blood lymphocytes is different, at least in part, from other agonists, such as concanavalin A in polymorphonuclear neutrophils which can trigger both the activation of p72syk and intracellular calcium mobilization. PMID- 8200460 TI - Peroxynitrite causes calcium efflux from mitochondria which is prevented by Cyclosporin A. AB - Superoxide reacts with nitric oxide to form peroxynitrite, a potent oxidising agent which may contribute to tissue damage in pathological situations such as inflammation and ischaemia/reperfusion. One mechanism by which oxidative stress damages tissues is the induction of a specific Cyclosporin A-sensitive mitochondrial calcium efflux pathway. Here we show that peroxynitrite induces calcium efflux from mammalian mitochondria and that this efflux is blocked by Cyclosporin A. These data suggest that disruption of mitochondrial calcium efflux may contribute to tissue damage when superoxide and nitric oxide are present together in vivo. PMID- 8200461 TI - 11-Hydroxythromboxane B2 dehydrogenase is identical to cytosolic aldehyde dehydrogenase. AB - 11-Hydroxythromboxane B2 dehydrogenase purified from porcine kidney has been identified as cytosolic aldehyde dehydrogenase (EC 1.2.1.3). This identification is based on protein characteristics, sequence analysis of one proteolytic digest, blocked N-terminus, subunit molecular mass of 55 kDa, and enzymatic activities. The sequence difference with the human enzyme is 7.5% in the fragments analyzed (29 exchanges of 388 positions, corresponding to the expected species variability for cytosolic aldehyde dehydrogenase). The substrate thromboxane B2 contains a hemiacetal in its ring structure, but the reaction most likely proceeds via the aldehyde form of the substrate. This finding is in agreement with the proposed metabolism of 4-hydroxycyclophosphamide and highlights the possibility that molecules containing a hemiacetal structure can function as substrates for aldehyde dehydrogenase. PMID- 8200462 TI - Prevention of adhesions. AB - A survey is given on the literature of the prevention of adhesions. Various methods of adhesion prevention are discussed: limitation of peritoneal injury, inhibition of the inflammatory response, prevention of coagulation of fibrinogen, removal of fibrin and mechanical separation of injured mesothelial surfaces. PMID- 8200463 TI - Differences in obstetrical intervention rates between Dutch hospitals. AB - Within the framework of the project 'Obstetric Peer Review' (Verloskundige Onderlinge Kwaliteitsspiegeling, VOKS) differences between Dutch hospitals concerning various obstetrical interventions were investigated. Using data of the Perinatal Database of the Netherlands from hospitals with at least 2000 newborns in the 5-year period 1987-1991, remarkable differences in frequencies of labour induction, caesarean section and vaginal operative deliveries can be shown, even when these interventions were considered within homogeneous subgroups with respect to pregnancy- or delivery-related complications. The incidence of caesarean section (and labour induction and vaginal operative delivery) appeared to depend more on the specific hospital policy than might be explained by populations differences alone. These intervention differences between hospitals clearly demonstrated the need to carry out a multivariate analysis to compare hospitals in a relevant and unbiased way, while adjusting for these population differences. This will estimate the intervention risks in a way which allows a fair comparison of hospital intervention policies. PMID- 8200464 TI - Perinatal results of hemodynamic and conservative temporizing treatment in severe pre-eclampsia. AB - OBJECTIVE: To evaluate maternal and perinatal outcome of hemodynamic temporizing management in severe pre-eclampsia. DESIGN: Study group of 57 pre-eclamptic women, gestational age 35 weeks or less, treated with plasma volume expansion and vasodilatation under invasive hemodynamic monitoring, retrospectively matched with a control group treated in another center without volume expansion and invasive monitoring. RESULTS: In both groups pregnancy was prolonged with 10-11 days. Maternal morbidity was low in both groups. No complications of hemodynamic monitoring were observed. Perinatal mortality was not significantly different between the study group (7.1%) and the control group (14.3%). SGA-infants were significantly less frequent in the study group (9%) than in controls (33%). CONCLUSION: Temporizing treatment of patients with early severe pre-eclampsia, with or without plasma volume expansion and invasive hemodynamic monitoring, may reduce neonatal mortality and morbidity. The difference in birthweight between study group and control group may be an effect of the therapy or may be caused by selection bias. The perinatal outcome in the study group suggests that there may be a subgroup of patients who might benefit from hemodynamic treatment. PMID- 8200465 TI - Cordocentesis for rapid karyotyping in fetuses with congenital anomalies or severe IUGR. AB - The objective was to determine the role of percutaneous umbilical blood sampling (cordocentesis) as a rapid technique for chromosome analysis in a high risk obstetric population. Cordocentesis was attempted in 167 pregnant women (168 fetuses) with IUGR, a single anomaly or multiple anomalies. Gestational age ranged between 17 and 37 weeks. The procedure was successful in 152 (90%) fetuses with a blood sample withdrawan at first attempt in 80%. Neither technique was associated with any false negative or false positive findings. Postprocedural complications included one case of persistent fetal bradycardia, but no fetal death. In nine cases amniotic fluid was collected, resulting in 161 fetal blood or amniotic fluid samples for chromosome analysis. An abnormal chromosome pattern (n = 26) was established in 1/12 cases (8%) of severe IUGR, 6/88 cases (7%) with a single structural anomaly and 19/61 cases (31%) with multiple structural anomalies. In the presence of an abnormal chromosome pattern, the perinatal mortality rate was as high as 96%. There is a high association between multiple fetal anomalies and abnormal chromosome pattern. PMID- 8200466 TI - Induction of labour by balloon catheter with extra-amniotic saline infusion (BCEAS): a randomised comparison with PGE2 vaginal pessaries. AB - OBJECTIVE: A new method for induction of labour--balloon catheter with extra amniotic saline infusion (BCEAS)--is evaluated in randomised comparison with prostaglandin E2 (PGE2) in vaginal pessaries. STUDY GROUP: One-hundred and nine pregnant women with unfavourable cervices. MAJOR OUTCOME MEASURES: The efficiency of inducing vaginal delivery and the level of 'disadvantages following induction of labour' (DisFIL scorings). RESULTS: Overall, BCEAS was less efficient inducing vaginal delivery than vaginal PGE2 (P < 0.01) because of a significant difference among parous women (P < 0.01). In the (larger) primiparous women group, and particularly in the subgroup of these having very low pelvic scores (Lange score, < or = 3), the efficiencies of the two methods were equal (P = 0.06) and P = 0.55, respectively). The levels of DisFIL scorings were not significantly different. However, higher rates of caesarean section followed BCEAS than PGE2 (29% and 10%, respectively; P < 0.05). Serious infectious complications were not recorded following BCEAS. No difference was apparent in the status of the neonates (judging from Apgar scores and umbilical artery pH and SBE). The women, delivering vaginally, commented the two methods equally favourably. CONCLUSION: BCEAS was less efficacious than vaginal PGE2 pessaries, though among primiparous women, especially those with very unfavourable cervices, the difference was not significant. Further refinements of the method are suggested. PMID- 8200467 TI - Management of stage III and IV endometriosis: a 10-year experience. AB - A retrospective analysis is reported of the management of 117 cases of infertility associated with Stage III and IV endometriosis. Combined medico microsurgical treatment was selected in 75.3% of Stage III cases and in 83.3% of those on Stage IV. Medication consisted of medroxyprogesterone acetate in 26 patients and danazol in the remaining 64. Microsurgery alone was utilized in 24.7% of Stage III patients and in 16.6% of those on Stage IV. Both surgery alone and the combined therapy had a profound positive effect on subjective symptoms: dysmenorrhea, dyspareunia and pelvic pain. Following combined therapy, pregnancy was achieved in 34.4% of all women. Respective figures are 30.7% for medroxyprogesterone acetate (29.4% Stage III and 33.3% Stage IV) and 35.9% for danazol (37.7% Stage III and 27.2% Stage IV). In the group of patients treated by surgery alone, pregnancy occurred in 25.9%. Of the pregnancies in women with Stage III endometriosis, 25 were carried to term and 6 ended with a spontaneous abortion; figures for Stage IV women are 5 and 2, respectively. Second-look laparoscopy was performed in 49 of the 79 patients who failed to conceive, at 12 36 months after treatment; persistent genital pathology, to which infertility could be attributed, was found in 77.5% of them. PMID- 8200468 TI - Efficacy on hyperandrogenism and safety of a new oral contraceptive biphasic formulation containing desogestrel. AB - A new biphasic oral contraceptive (OC) containing ethinylestradiol and desogestrel (DGS) in both phases of the cycle (7 days 40/25 micrograms + 15 days 30/125 micrograms) was tested for its reliability, tolerability, safety and effectiveness on endocrine correlates of hyperandrogenism and acne in normal women (n = 30) and women suffering from acne (n = 33). Contraceptive efficacy was absolute and, despite 3 drop-outs in the group with acne (4.7% of total patients), subjective complaints were limited to a small number of women. Cycle control was satisfactory in both groups. Fibrinopeptide A remained stable under the treatment, whereas HDL-chol increased and the ratio between LDL-chol and HDL chol decreased during pill intake. Other advantageous effects were obtained on the circulating androgen profile with increased sex hormone binding globulin concentrations coupled with significantly reduced total and free testosterone levels. In 23 out of 30 patients with acne (76.6%) the skin disease disappeared after 9 months of therapy and in 3 severely affected subjects the pathology changed into a pattern of mild or moderate degree. Our results indicate that the tested new biphasic OC combination is reliable, well tolerated, safe and effective against hyperandrogenism. PMID- 8200469 TI - Pregnancy and paroxysmal nocturnal hemoglobinuria. AB - A patient is described who developed symptoms of paroxysmal nocturnal hemoglobinuria (PNH) in her first pregnancy. This was uneventful except for a spontaneous preterm delivery. The second pregnancy was complicated by severe anemia and a hemolytic crisis with Budd-Chiari syndrome at 31 weeks' amenorrhoea. Delivery was again preterm and was the result of induced labour after premature rupture of membranes at 34 weeks. Literature shows a high maternal mortality among PNH patients (5.8%). The most common cause of death is liver vein thrombosis (Budd-Chiari syndrome). Fetal wastage (30%) and prematurity rate (16%) are also high. Recommendations for follow-up and therapy are given such as anticoagulation therapy, platelets and washed erythocytes transfusions, screening for Budd-Chiari syndrome and infections. PMID- 8200470 TI - 'Forgotten' intrauterine device leading to actinomycotic pyometra--13 years after menopause. AB - A case of a 'forgotten' intrauterine device (IUD) in a postmenopausal woman leading to Actinomyces israelii infection and pyometra is described. The patient was asymptomatic for 22 years after IUD insertion and developed the complications 13 years after menopause. To prevent such serious complications, it is important to ensure that intrauterine devices, once they have served the purpose and even if they are asymptomatic, are removed. PMID- 8200471 TI - Twin pregnancy involving complete hydatidiform mole and partial mole after five years of amenorrhoea. AB - A case of twin pregnancy involving a single fetus and complete hydatidiform mole in a 56-year-old woman after 5 years of amenorrhoea is reported. The patient presented with threatened abortion and was managed with bed rest and blood transfusion. Six weeks after admission and at 20 weeks gestation, she had a spontaneous vaginal delivery of a molar pregnancy and a fresh stillbirth with molar degeneration of the placenta. The uterine cavity was evacuated by suction curettage after delivery and plasma, BHCG was negative 4 weeks subsequently. In a case of pregnancy after a long period of amenorrhoea in the older woman, molar degeneration is a strong probability. PMID- 8200472 TI - Artificial parthenogenesis in starfish eggs: behavior of nuclei and chromosomes resulting in tetraploidy of parthenogenotes produced by the suppression of polar body extrusion. AB - Artificial parthenogenesis in starfish requires the activation of oocytes and the suppression of the polar body (PB) extrusion. To induce parthenogenesis we have employed a combination of calcium ionophore A23187 for activating oocytes and cytochalasin B (CB) for the suppression of PB extrusions. The treatment of activated oocytes with CB during meiosis I produced eggs lacking polar bodies, i.e., during meiosis I produced eggs lacking polar bodies, i.e., 0pb eggs, and treatment during meiosis II induced eggs bearing the first PB only, i.e., 1pb eggs. About 90% of both 0pb and 1pb eggs developed parthenogenetically with strong synchrony of cell division among eggs. After meiotic chromosomes in CB treated oocytes separated finally into monads, they came together to form a single nucleus. The nucleus was found to be tetraploid in the 0pb eggs and diploid in the 1pb eggs. Regardless of the difference in ploidy, both 0pb and 1pb eggs developed as tetraploid embryos. Observations of the behavior of meiotic chromosomes and nuclei revealed that in the 0pb eggs, the first round of chromosomal replication was followed by the first cleavage, as in normally fertilized eggs. In the 1pb eggs, on the other hand, two rounds of chromosomal replication were found to precede the first cleavage, indicating the occurrence of one (first) round of chromosomal replication that is not accompanied with cytokinesis. In the first round of mitosis, a bipolar spindle did not appear, but only a half spindle was formed, resulting in the failure of both karyokinesis and cytokinesis. Thus, both types of parthenogenetic eggs became tetraploid before the first cleavage. At the first cleavage, both types of eggs formed a bipolar spindle and divided into a pair of blastomeres. Based on these observations, we suggest that the meiotic centrosomes remaining in these eggs by the failure of PB extrusion are diverted into mitosis-organizing centers in the mitotic spindle, and this results in parthenogenetic development. PMID- 8200473 TI - Spontaneous loss of interstitial stem cells from hydra tissue. AB - A spontaneous loss of interstitial stem cell population from normal hydra tissue was observed. A wild-type strain of Hydra magnipapillata was maintained in lines of individual polyps for many generations. In each line, the first generation was started from a single young polyp, and the first bud produced in one generation was used to start the next generation. Many lines maintained in this way (10/16) yielded polyps which exhibited limited feeding capacity, indicating reduced numbers of nematocytes and/or nerve cells in the tissue. Furthermore, a few lines (3/16) turned into "epithelial hydra" which could not move or feed and contained no interstitial stem cells or their differentiation products (nematocytes and nerve cells) in the tissue. Examination of the number and localization of interstitial cells in the tissue of various lines provided evidence which suggests that multiple factors, including reduced displacement of interstitial cells from parental to bud tissue, are responsible for the spontaneous loss of interstitial stem cell population observed. PMID- 8200474 TI - Cell-type-specific nuclear translocation of fibroblast growth factor-2 isoforms during chicken kidney and limb morphogenesis. AB - Analysis of the fibroblast growth factor-2 (FGF-2 or bFGF) proteins during chicken embryonic pattern formation and organogenesis revealed that three isoforms (18.5, 20.0, and 21.5 kDa) were synthesized by alternative translation initiation from one coding region. A highly specific antiserum was raised and used for studying the temporal and spatial distribution of the FGF-2 isoforms during chicken embryogenesis. The distribution of FGF-2 proteins during limb pattern formation has been unraveled. Their presence in both ectodermal and mesenchymal cells is consistent with an involvement in regulating the balance of growth and differentiation. High levels of FGF-2 proteins were furthermore detected in all epithelial cells of the developing kidney from the pronephric stage onward. The proteins were in general predominantly cytoplasmic, but a specific subpopulation of limb mesenchymal cells and kidney epithelial cells (podocytes) showed a striking nuclear localization. Nuclear translocation of the FGF-2 proteins occurred in differentiating podocytes of meso- and metanephric glomeruli and was maintained in adult kidneys. These results, in contrast to previous in vitro studies, revealed that nuclear accumulation of FGF-2 proteins is restricted to few specific cells during embryogenesis. PMID- 8200475 TI - Developmentally regulated expression of a mouse germ cell nuclear antigen examined from embryonic day 11 to adult in male and female mice. AB - A rat IgM monoclonal antibody has been developed which recognized a mouse germ cell nuclear antigen (GCNA1). GCNA1 is present in prospermatogonia (gonocytes) in males and in oogonia and oocytes of females within the gonadal ridge from Embryonic Day 11.5 onward, but rarely in primordial germ cells prior to their arrival at the gonadal ridge. Immunolocalization demonstrates that GCNA1 is abundant in nuclei of spermatogonia and early spermatocytes, but decreases during subsequent spermatocyte and round spermatid development, and is not detected beyond step 10 elongating spermatids. The antigen is approximately 80-110 kDa on immunoblots of isolated pachytene spermatocytes and round spermatids. However, GCNA1 appears to be absent from sperm in the epididymis and vas deferens, Sertoli cells, TM3 cells (Leydig-like) and TM4 cells (Sertoli-like), lung, liver, kidney, spleen, heart, skin, brain, epididymis, and ovary. GCNA1 is present in prepuberal male mice (Days 2-14) in all stages of prespermatogonial and spermatogonial development. It is also present in prepuberal male mice (Days 2-14) in all stages of prespermatogonial and spermatogonial development. It is also present in oocytes of neonatal females until Postpartum Day 12. GCNA1 is first lost from oocytes in the medulla of the ovary as they arrest at the dictyate stage and gain a layer of granulosa cells. In addition, antigen is present in moderate amounts in F9 embryonal carcinoma cells and SCC-PSA1 pluripotent terato-carcinoma cells. Thus, GCNA1 serves as a common marker of the germ cell lineage in male and female mice after primordial germ cells arrive in the gonadal ridge until they reach the diplotene/dictyate stage of the first meiotic division. PMID- 8200476 TI - Alterations in protein synthesis following transplantation of mouse 8-cell stage nuclei to enucleated 1-cell embryos. AB - Enucleated mouse 1-cell embryos arrest development at the 2-cell stage following transplantation of cleavage stage nuclei. Earlier studies employing one dimensional protein gel electrophoresis failed to reveal obvious differences in gene expression in the manipulated embryos that might account for this block. We report here the results of a quantitative, two-dimensional gel electrophoretic analysis that reveals at least 50 alterations in protein synthesis in the 8-->1 cell nuclear transplant embryos. Approximately half of these alterations involve proteins that normally decrease in synthesis between the 2-cell and 8-cell stages and half involve proteins that are synthesized constitutively between these two stages. These results are the first to reveal significant biochemical alterations that accompany the morphological and cytological differences previously described and indicate that the 8-cell stage nucleus is unable to completely recapitulate the normal progression of changes in protein synthesis pattern that occur during the 2-cell stage. Our results indicate that developmental arrest may result from a combination of (1) failure to re-activate genes that normally become repressed between the 2-cell and 8-cell stages and (2) failure to up-regulate genes that become repressed during reprogramming of the 8-cell nucleus by the 1-cell cytoplasm. The failure to up-regulate the synthesis of proteins expressed at both the 2-cell and the 8-cell stages may indicate that, for some genes, a transcriptionally inactive state, possibly related to a particular chromatin configuration, may serve a protective function by restricting access of factors that can permanently reduce the ability of a gene to be expressed. This may partially account for the need to delay the widespread activation of zygotic gene transcription until the 2-cell stage, when much of the nuclear remodeling that occurs postfertilization is complete. PMID- 8200477 TI - DNA-protein interactions in the Caenorhabditis elegans embryo: oocyte and embryonic factors that bind to the promoter of the gut-specific ges-1 gene. AB - We describe an experimental system in which to investigate DNA-protein interactions in the early Caenorhabditis elegans embryo. A homogeneous population of developmentally blocked mid-proliferation stage embryos can be produced by exposure to the deoxynucleotide analog fluorodeoxyuridine. These blocked embryos remain viable for days and express a number of biochemical markers of early differentiation, for example, gut granules, the gut esterase ges-1, and two regulatory genes, mab-5 and hlh-1. Using the techniques of gel mobility shift and DNase I footprinting, we show that nuclear extracts prepared from these embryos contain factors that bind to the 5'-promoter sequences of the C. elegans gut specific ges-1 gene. In particular, we examine a putative gut "activator" region, which was previously identified by deletion-transformation analysis and which contains two copies of a consensus GATA-factor binding sequence. Factors that bind to double-stranded oligonucleotides containing the ges-1 GATA sequences are present predominantly in nuclear extracts of embryos but are found neither in cytoplasmic nor in nuclear extracts of unfertilized oocytes. Two proteins, of 43 and 60 kDa, can be uv-crosslinked to double-stranded oligonucleotides containing the ges-1 GATA sequences. The sizes of these proteins correspond to the sizes expected for the elt-1 protein and for the skn-1 protein, two regulatory factors present in early C. elegans embryos and possible candidates for ges-1 control. However, we show that homozygous deficiency embryos (mDf7/mDf7 embryos and eDf19/eDf19 embryos, both of which lack the elt-1 gene, and nDf41/nDf41 embryos, which have no skn-1 gene), still express the ges-1 esterase. We conclude that neither the elt-1 gene nor the skn-1 gene is necessary zygotically for ges-1 expression. We suggest that neither the elt-1 protein nor the skn-1 protein interacts directly with the ges-1 gene and that the observed binding proteins must correspond to products of other genes. More generally, the present experimental system should allow the biochemical study of any gene expressed during early C. elegans embryogenesis. PMID- 8200478 TI - A small region surrounding the distal promoter of the hunchback gene directs maternal expression. AB - While maternally provided factors play essential roles in the earliest processes of embryogenesis, little is known about the control of female germline-specific gene expression. Primer extension analysis and in situ hybridization experiments demonstrate that in adult Drosophila females, transcripts of the gap gene hunchback (hb) are produced only by the distal (P1) promoter and that this expression is largely restricted to the ovarian nurse cells. A deletion analysis of the hb promoter using lacZ reporter constructs defines a 1.2-kb genomic DNA fragment surrounding the P1 promoter that is sufficient to reproduce the wild type pattern of hb ovarian transcript accumulation. By contrast, the subfragments of this region we have tested fail to direct specific ovarian expression. PMID- 8200479 TI - A model of neurite extension across regions of nonpermissive substrate: simulations based on experimental measurement of growth cone motility and filopodial dynamics. AB - The guidance of pioneer neurites in the developing embryo occurs through a variety of mechanisms, including chemotaxis, haptotaxis, contact inhibition, and mechanical guidance. In each of these processes, the growth cone serves as a sensory-motile mediator of the neurite response to a directional cue. However, the role of growth cone dynamics in determining the neurite path is not well defined. To provide a quantitative basis for investigating this relationship, we have developed a mathematical model that describes two major aspects of growth cone motility during neurite outgrowth: the continuous but erratic motion frequently observed on homogeneous substrates such as laminin or collagen and the more directed movement along filopodial that have contacted a remote cue. Model parameters include the rate and angle of filopodial initiation, rates of filopodial extension and retraction, maximum filopodial length, and the root-mean square speed and directional persistence time of growth cone advance. Experimental estimates of these parameters were obtained from in vitro measurements on chick dorsal root ganglion and rat superior cervical ganglion neurons and used to compare model results with previously reported experimental data for neurite outgrowth on a patterned laminin/albumin substrate. The model represents a conceptual framework for further investigation and elucidation of the role of growth cone dynamics in neurite outgrowth and guidance. PMID- 8200481 TI - Disruption of the gene encoding the EcmA, extracellular matrix protein of Dictyostelium alters slug morphology. AB - The ecmA and ecmB genes of Dictyostelium are expressed in prestalk and stalk cells. They encode components of the slime sheath, the extracellular matrix that surrounds the migrating slug, and the stalk tube, the matrix that encases stalk cells. We have generated, by homologous gene disruption, a mutant in which the ecmB gene is inactivated but the strain develops normally. In contrast, ecmA null mutant strains develop to form abnormally long and thin standing slugs. While the slime sheath of mutant slugs appears to be normal in electron microscopic observations, the sheath material remaining on the substratum after the slug travels through it is abnormally susceptible to breakage. After a short period of migration the axial ratio of mutant slugs decreases to that of normal slugs and, at culmination, normal fruiting bodies are produced. These data suggest that the EcmA protein has its primary role during slug formation, where it contributes to the strength of the slime sheath, and that the function of the EcmB protein is dispensible. PMID- 8200480 TI - Assembly of myotendinous junctions in the chick embryo: deposition of P68 is an early event in myotendinous junction formation. AB - Myotendinous junctions (MTJs) are specialized sites at the surface of muscle fibers where force is transmitted between muscle and tendon. Morphogenesis of MTJs in the latter half of embryonic chick development is characterized by formation of basement membrane, appearance of subsarcolemmal densities, association of myofibrils with the membrane, and then membrane folding. In the present investigation, the time of appearance of proteins involved in force transmission at MTJs is compared to those previously described structural specializations occurring during MTJ development. In addition, P68, a recently discovered collagen-binding protein that is shown to be identical or closely related to laminin-binding lectin is also demonstrated at MTJs, and an improved technique for P68 purification is presented. P68 accumulates on the surface of collagen fibers that lie near the ends of myotubes in chick hindlimb muscle prior to the appearance of ultrastructurally discernible basement membrane. At Day 10, the stage when MTJ basement membrane is first discernible by electron microscopy, laminin and the beta 1 subunit of integrin are detectable at the MTJ. At this stage, laminin distribution coincides with P68 distribution and no laminin is detectable at sites other than the forming MTJs. Fibronectin is detectable at the MTJ at Day 12, but is not enriched at the MTJ relative to other sites on the myotubes. At Day 13, the stage at which subsarcolemmal densities first appear, talin is demonstrable at the MTJ and fibronectin concentration at the MTJ is enriched. Collagen type IV cannot be discerned at the MTJ until Day 15. Thus, the earliest demonstrable specializations at sites of MTJ formation are: (1) the appearance of P68 on collagen fibers that lie at the ends of myotubes, which occurs prior to ultrastructurally discernible specializations at the MTJ and (2) the accumulation of laminin at the MTJ with a distribution identical to that of P68 at the stage of MTJ formation in which basement membrane first appears. These findings indicate that P68 and laminin may mediate early events in MTJ assembly. PMID- 8200482 TI - Role for short-range interactions in the formation of cartilage and muscle masses in transfilter micromass cultures. AB - In the embryonic limb bud, chondrogenic and myogenic regions arise by segregation from a mixture of chondrogenic and myogenic precursor cells (Schramm and Solursh, 1990). In in vitro micromass cultures, dissociated limb bud cells also segregate into chondrogenic and myogenic tissues. The process of segregation was studied using transfilter micromass cultures to determine the role of short-range interactions in the formation of these two tissue masses. Limb bud cells were plated on both sides of large and small Nucleopore filters. Pore size was chosen to permit cell-cell or cell-extracellular matrix contact across large pore filters but permit only interactions via diffusible molecules across small pore filters. Cultures were plated at high density on one surface to allow formation of chondrogenic nodules and at high or low density on the opposing surface to observe any segregation effect on chondrogenic and myogenic cells, respectively. Spatially organized extracellular matrix of micromass cultures was fixed by cold ethanol precipitation onto filters. The fixed micromass cultures lost the ability to affect segregation across the filter. These results suggest that chondrogenic aggregates enlarge in an autocrine manner dependent on direct cell-cell or cell extracellular matrix contact provided by living cells. Myogenic segregation likely occurs in a paracrine manner that also requires short-range interactions. PMID- 8200483 TI - Mammalian adrenal chromaffin cells coexpress the epinephrine-synthesizing enzyme and neuronal properties in vivo and in vitro. AB - Adrenal chromaffin cells and neurons of the sympathetic ganglia are derived from common precursors in the neural crest. The phenotype of the sympathoadrenal progenitor cell is unknown, but adult chromaffin cells are distinguished by the expression of phenylethanolamine-N-methyltransferase (PNMT) and the lack of neurofilament (NF) and neuritic processes. Mature neurons have processes and express NF, but are PNMT-. We hypothesize that embryonic adrenal cells are multipotential. This implies that the cells can coactivate all the traits characteristic of mature sympathetic neurons and chromaffin cells and then selectively extinguish expression of either the chromaffin or the neuronal traits, depending on the environment. We further asked whether this repression is plastic and can be environmentally modified in adult chromaffin cells. We demonstrate that, in vivo, embryonic (e-) rat adrenal cells coexpress PNMT and the intermediate- and high-molecular-weight neurofilaments at e-15.5 (21%), e 16.5 (40%), and e-20.5 (23%). When cultured in complete or glucocorticoid depleted media for 5 to 14 days, 20% of adult bovine chromaffin cells which remain PNMT+ reexpress NF and extend NF+ and PNMT+ processes. Both the expression of NF and the extension of neurites are inhibited by the addition of 10(-7) M dexamethasone to complete media. We conclude that the embryonic adrenal medullary cells simultaneously express traits of mature chromaffin cells and neurons and that the phenotypes remain labile in the adult mammalian chromaffin cell. In addition, coexpression of PNMT, NF, and neurite extension are not mutually exclusive in either the embryonic or adult adrenal chromaffin cell. PMID- 8200484 TI - Cholinergic neuronal differentiation factor (CDF)/leukemia inhibitory factor (LIF) binds to specific regions of the developing nervous system in vivo. AB - The cholinergic neuronal differentiation factor (CDF)/leukemia inhibitory factor (LIF) promotes survival and/or differentiation of specific neuronal populations in vitro. To investigate the spatial and temporal distribution of CDF/LIF binding sites in the developing rat nervous system, we localized binding of iodinated native rat CDF/LIF by radioautography. We find that specific CDF/LIF binding sites are present in distinct regions of the nervous system at defined developmental stages. CDF/LIF binding is detectable in all sensory ganglia examined, both neural crest- and placode-derived, and in all sympathetic and parasympathetic ganglia examined. In the central nervous system, in contrast, binding is restricted to specific regions in the motor, sensory, and limbic systems. These in vivo results not only support culture studies which suggest CDF/LIF involvement in development of specific populations of neurons, but also suggest new roles played by CDF/LIF. PMID- 8200485 TI - MAP kinase is activated during mesoderm induction in Xenopus laevis. AB - MAP kinase (MAPK) is activated in animal cap explants from Xenopus embryos in response to mesoderm induction by FGF. This activation is rapid, appearing within 1 min of treatment with FGF, and prolonged, lasting for at least 2 hr. By immunoblot analysis, this activation of MAPK is coupled with an electrophoretic shift to the slowly migrating, phosphorylated form of MAPK. Activin-stimulated mesoderm induction also results in the activation of MAPK, but only upon prolonged exposure. However, activin can potentiate the activation of MAPK by FGF as early as 1 min after administration. These findings suggest that MAPK is involved in the early signaling events of FGF-mediated mesoderm induction, and this involvement is modulated by other mesoderm inducers such as activin. PMID- 8200487 TI - Cardiorespiratory functioning of preterm infants: stability and risk associations for measures of heart rate variability and oxygen saturation. AB - Cardiorespiratory measures are used with increasing frequency to assess individual differences in development in full-term and preterm infants, yet little information exists concerning the stability of these measures or their relations to each other. This study assessed three common cardiac measures (heart period, heart period variability, and vagal tone) and two measures of arterial oxygenation based on pulse oximetry (mean pulse oxygen saturation and variability) in a sample of 35 preterm infants. Data were collected on five occasions: on 3 consecutive days in the early neonatal period, at 34 weeks postconceptional age, and at discharge. Results indicate both short-term and longer term stability for all cardiac measures. Oxygen saturation demonstrated only short-term stability prior to 34 weeks. Mean heart period was positively associated with both measures of heart period variability at each assessment point, while mean oxygen saturation level was inversely related to oxygen saturation variability. In addition, significant associations between cardiorespiratory patterns and perinatal risk measures were found. It is concluded that these measures reflect stable characteristics of neuroregulatory function in preterm infants. PMID- 8200486 TI - Involvement of hepatocyte growth factor in kidney development. AB - Using PCR, hepatocyte growth factor (HGF) and c-met (HGF receptor) expression were analyzed in the developing mouse kidney. Both HGF and c-met were expressed from Gestational Day 11.5 onward, the time at which branching morphogenesis of ureteric bud occurs. Coculturing the embryonic kidney with MDCK cells seeded in Type I collagen induced branching morphogenesis of the MDCK cells. When a monospecific antiserum against HGF was included in the culture medium, the branching morphogenesis induced by the embryonic kidney was markedly inhibited (73%). This anti-HGF serum also inhibited metanephric growth when incubated with 11.5- to 12.5-day embryonic kidneys in an organ culture assay. No inhibition was observed by nonimmune serum. Perturbation of ureteric duct development as well as extraductal metanephric development was observed in embryonic kidneys incubated with the anti-HGF serum. Together, our data indicates an important role for HGF in kidney development. PMID- 8200488 TI - The development of head position preference in preterm infants beyond term age. AB - Healthy full-term infants show a developmental trend in head position from an initial right-sided preference to one with the head in midline around the age of 12 weeks. We studied the effects of intrauterine growth retardation (IUGR) and the degree of prematurity on both aspects of development from 35 weeks postmenstrual age to 18 weeks corrected age in 35 preterm infants without overt neurological abnormalities and whose gestational ages ranged from 27 to 34 weeks. Our data reveal that, during the preterm period, infants born after pregnancies of 32 weeks or less showed a lack of right-sided preferences for head turning after release from midline but not for the subsequent maintenance of a position. IUGR did not seem to affect either preference. After term age a right-sided preference diminished while a head midline position increased. The latter was not significantly delayed in relation to birth before 32 weeks gestation or IUGR. However, when infants were classified on the basis of neurological differences as reflected in a (mildly) abnormal movement quality, a delay in the attainment of a midline posture was observed, which suggests it is related to a suboptimal neurological condition. This delay, however, was also accounted for by the side to-side flattening of the skull. PMID- 8200489 TI - Specific postnatal auditory stimulation interferes with species-typical visual responsiveness in bobwhite quail chicks. AB - The effects that a manipulation of sensory experience may have on perceptual development are likely to depend on a number of factors, including the amount and the type of stimulation provided. To examine the relative influence of these stimulation factors on early perceptual organization, this study exposed bobwhite quail hatchlings to augmented amounts of bobwhite chick distress calls, bobwhite chick contentment calls, domestic chicken distress calls, or no additional auditory stimulation during the first 72 hr following hatching. Results showed that bobwhite hatchlings exposed to bobwhite chick distress calls do not exhibit species-typical visual responsiveness to maternal cues. In contrast, bobwhite hatchlings exposed to bobwhite chick contentment calls, domestic chicken hatchling distress calls, or no augmented auditory stimulation exhibited species typical auditory and visual responsiveness to maternal cues. These results demonstrate intermodal effects of postnatal sensory stimulation and suggest that specific types of postnatal auditory stimulation, rather than simply increased amount of stimulation, are necessary to interfere with species-typical intersensory functioning. PMID- 8200490 TI - Intracerebroventricular injection of renin in the neonatal rat reveals a precocious sodium appetite that is dissociated from renin-aroused thirst. AB - Previous research on the ontogeny of sodium appetite in the rat has shown that sodium deficit first engenders sodium intake at 12 days of age, whereas direct stimulation of the brain renin--angiotensin system by intracranial injection of renin increases intake of NaCl solution as early as 3 days postnatally. Similar activation of brain angiotensin also increases thirst, so that the specificity of the precocious sodium intake remains undetermined. In this article we report experiments that dissociate neonatal renin-evoked sodium appetite and thirst, and establish the specificity of the appetite. Our findings confirm that sodium appetite can first be discerned at 3 days of age, and show that it rapidly develops until 12 days of age. During this developmental window, renin-evoked sodium appetite is dissociated from thirst because (a) NaCl is preferred to water, (b) the appetite develops faster than thirst, and (c) 3-day-old renin stimulated pups will avidly lick dry NaCl. These results show that activation of brain angiotensin in the 3-day-old rat pup evokes a precocious and specific sodium appetite. PMID- 8200491 TI - [Thallium-dipyridamole in acute myocardial infarction treated by thrombolysis: diagnostic and prognostic value]. AB - BACKGROUND: The management of patients who received thrombolytic therapy for acute myocardial infarction is still controversial. It is not clear if the strategies usually followed after myocardial infarction for risk stratification have the same value when applied to patients treated with thrombolysis. METHODS: To assess the diagnostic and prognostic value of dipyridamole thallium-201 scintigraphy in the "thrombolytic era", we studied 110 consecutive patients younger than 75 recovering from first uncomplicated acute myocardial infarction treated with thrombolytic agents. Patients with early angina, recurrent acute myocardial infarction, heart failure, life-threatening arrhythmias, non Q wave myocardial infarction were excluded. Ninety patients were treated with streptokinase, 14 with rtPA, 6 with APSAC: All patients underwent dipyridamole thallium scintigraphy with standard dose and coronary angiography before discharge (10-20 days). Ninety-nine patients underwent exercise test. All patients were followed-up for 22 +/- 9 months (range 8-42). Perfusion abnormalities were classified as reversible (totally or partially) defects or persistent defects and within or outside the infarct zone. RESULTS: Fifty-eight patients developed anterior and 52 inferior acute myocardial infarction. Coronary angiography showed single vessel coronary artery disease in 66 patients, multivessel disease in 34, and normal coronary arteries or sub-critical stenosis in 10. No major complications (death, myocardial infarction, threatening arrhythmias, prolonged severe hypotension) occurred after dipyridamole infusion. Sixty-two patients had reversible perfusion defects at thallium scanning (34 within the infarct zone, 21 within and outside the infarct zone, 7 outside); 38 patients had persistent defects; 10 patients had a normal scintigraphic pattern. The diagnostic value of homozonal perfusion reversible defects for identifying a patent infarct-related vessel was poor (sensitivity 69.7%, specificity 64.7%). The diagnostic values of the same scintigraphic pattern improved in detecting patent infarct-related artery with residual critical stenosis (sensibility 75.4%, specificity 77.3%); in all the false positive cases (reversible defects within the infarct zone and occluded infarct-related artery) a good collateral flow was present. The sensitivity of reversible defects outside the infarct zone in detecting multivessel disease was 64.7% vs 56.3% of exercise test; the specificity was 92% vs 64%; the positive predictive value 78.6% vs 44%; the negative predictive value 85.3% vs 74.5%; the diagnostic accuracy 83.6% vs 61.4%. During the follow-up 2 deaths, 7 recurrent myocardial infarction, 1 sustained ventricular tachycardia, 1 heart failure, 13 recurrence of unstable angina and 9 revascularization procedures occurred among patients with reversible defects (either within or outside the infarct zone) at thallium scanning. One recurrent myocardial infarction, 4 recurrence of unstable angina and 2 revascularization procedures were the events among patients with persistent defects or normal scintigraphic pattern (p < 0.001). Ischemic events occurred with similar frequency in patients with reversible perfusion defects within the outside the infarct zone (55% vs 50%, NS). CONCLUSIONS: Dipyridamole thallium-201 scintigraphy performed after uncomplicated myocardial infarction treated with thrombolytic agents is a valuable diagnostic tool in identifying viable jeopardized myocardium within the infarct zone perfused by a patent but critically narrowed vessel; it shows better diagnostic accuracy in detecting multivessel disease than does the exercise test and is able to identify a subset of patients at risk for future ischemic events after thrombolytic therapy. PMID- 8200492 TI - [Heart arrest in acute pulmonary embolism. An anatomo-clinical study]. AB - The Authors describe the modalities and mechanisms of cardiac arrest (CA) in the course of acute pulmonary embolism (PE). Clinical data refer to 39 CA episodes occurred in 28 patients with massive or submassive PE; autopsy data are from 26 of 28 patients of the same series. One-third of 39 CAs proved at least momentarily reversible; two-thirds were irreversible. Data analysis showed that most CA episodes, reversible or otherwise, seen in the course of PE were due to electromechanical dissociation (EMD). In fact, EMD was responsible for 12 of 13 reversible CAs and 22 of 26 irreversible arrests. EMD usually follows shock, but may occur unheralded. When EMD-induced CA is at least temporarily reversible, the heart rate is often normal or high and QRS complexes are narrow. In most cases the sudden rise of right ventricular afterload came on top of a pre-existing myocardial damage, for the most part of ischemic, sometimes necrotic, origin. In this series, therefore, it seems quite difficult to tell "primary" from "secondary" forms of EMD. External cardiac massage continued for as long as 40 minutes was associated in some cases with a bolus fibrinolytic infusion within minutes from occurrence of CA. Five of 7 patients so treated made a temporary recovery and two survived; at autopsy, none of the 5 patients who died showed any evidence of bleeding attributable to local injury. PMID- 8200493 TI - [Percutaneous closure of interatrial defect using the buttoned double-disk prosthesis]. AB - BACKGROUND: Surgical repair is the procedure of choice for atrial septal defect correction. Even though surgical mortality is low (< 1%), morbidity is significant (anesthesia, thoracotomy, cardiopulmonary bypass, longer hospitalization and intensive care unit monitoring). Transcatheter methods to occlude atrial septal defects have been in development during the last two decades. We report our experience in Italy with the Sideris buttoned double-disk device. METHODS: From March 1992 to April 1993, 14 patients aged 20 months to 52 years, weight 10 to 82 kg, underwent transcatheter atrial septal defect occlusion with the Sideris buttoned device. The buttoned device is a miniaturized two disk device introduced through small venous sheaths (8-9 F). The diameter of atrial septal defects by echocardiography varied between 9 and 23 mm, while the balloon stretched diameter of the defects varied between 13 and 24 mm. The devices selected were 19 +/- 4 mm larger than the stretched diameter of the defect, but less than the total length of the septum (33-56 mm) by echo. RESULTS: Pulmonary to-systemic flow ratio varied between 1.5 to 4.0. Mean pulmonary artery pressure varied between 10 and 24 mmHg (mean value 17 +/- 3.5 mm Hg). The relationship between different atrial septal defect measurements (echo, shunt flow, stretched diameter) was statistically analysed: transthoracic echo diameter had a good correlation with the balloon stretched diameter (r = 0.63, p < 0.001). The atrial septal defect was occluded in 12 patients (86% success rate). There was one early "unbuttoning" which was surgically corrected with success. The other patient underwent surgical correction 3 months later because of unsuitability for transcatheter closure. Minimal residual shunt detected by color flow mapping at 1 month follow-up was seen in 4 patients (33%). No complications occurred in any of our patients. CONCLUSIONS: This initial experience with the Sideris buttoned double-disk device demonstrated that transcatheter closure of atrial septal defect is feasible and effective. It can be accomplished through small introducing sheaths. Further clinical trials are justified. This method could become the procedure of choice for the correction of small ASDs. PMID- 8200494 TI - [Coronary vasomotor response to acetylcholine correlates with plasma levels of cyclosporin and triglycerides in patients with heart transplantation]. AB - BACKGROUND: Vasoconstriction of normal coronary arteries has been reported after intracoronary (i.c.) administration of acetylcholine (Ach) in cardiac transplant patients and has been related to early endothelial disfunction; the clinical correlates of this response are still unknown. METHODS: We infused graded i.c. concentrations of Ach in 32 pts with angiographically smooth coronary arteries 1 to 3 years after heart transplantation. Changes in diameters of the proximal and middle segments of the left anterior descending coronary artery were measured by quantitative coronary angiography (automatic edge detection). RESULTS: The response to Ach ranged from +44% to -58%; at linear regression analysis it was significantly related to the plasma levels of cyclosporine (r = -0.39, p < .05) and triglycerides (r = -0.42, p < .02) but not to vessel diameter, recipient and donor age, time after transplantation, hypertension, cholesterol levels, number of acute rejection episodes and previous cytomegalovirus infections. CONCLUSIONS: In heart transplant pts with angiographically normal coronary arteries i.c. Ach may reveal endothelial disfunction which is associated with high cyclosporine and triglycerides plasma levels. Whether this response may predict an earlier development of coronary disease remains to be elucidated. PMID- 8200495 TI - [Relationship between rheumatic disease and mitral valve prolapse: an etiopathogenetic connection or the result of a semiologic confusion?]. AB - The term mitral valve prolapse is used to describe either one of the pathophysiological mechanisms of mitral regurgitation or a distinct biological condition with a defined inherited basis, with or without mitral incompetence. In the former case, association with rheumatic fever is implied by the definition itself; in the latter it's questionable (rheumatic fever could act as an environmental factor in the expression of a genetically determined mitral valve prolapse). Three hundred and twenty patients with mitral valve prolapse, diagnosed as a primary one, were studied in order to assess the prevalence of a well-documented history of rheumatic fever: this resulted higher versus a control population (5.6% vs 0.9%-p < 0.01). The retrospective nature of the study does not allow a definite conclusion. Familial as well as long-term follow-up studies are necessary to better define the association between rheumatic fever and mitral valve prolapse; a potentially different prognosis, mainly accounting to the development of a clinically relevant mitral regurgitation in patients with mitral valve prolapse and previous rheumatic fever, has to be searched. PMID- 8200496 TI - Fetal hydrops due to right ventricular and tricuspid valve dysplasia. A case report. AB - We report a case of fetal hydrops at 32 weeks of gestation, diagnosed prenatally due to an unusual form of non-Ebstein dysplasia of the tricuspid valve and of the right ventricle, different from the classification used in the literature. Digoxin therapy, administered for two weeks in utero and then after the premature delivery, did not improve the massive right heart failure due to the tricuspid insufficiency, and the baby died at 4 days of life. PMID- 8200497 TI - [Anatomo-clinical and echocardiographic characteristics of cardiopathy in Friedreich's ataxia: description of a clinical case]. AB - A case of Friedreich's Ataxia in a 16-year-old patient is reported. Clinical, electrocardiographic and echocardiographic findings of this patient are described, along with the differential characteristics between hypertrophic cardiomyopathy in the course of Friedreich's Ataxia and the classic form of hypertrophic cardiomyopathy. Bidimensional echocardiography is able to identify cardiac alterations and to differentiate patients affected by Friedreich's ataxia from patients with other ataxic disorders where cardiac involvement is not present. PMID- 8200498 TI - [A case of double-chamber right ventricle operated on in adulthood]. AB - A 49-year-old patient suffering from recurrent effort lipothymia and palpitation was referred for cardiac catheterization. A diagnosis of marked hypertrophy of right ventricular outflow tract and double chamber right ventricle with intraventricular gradient of 50 mm Hg was made. Operation was delayed until age 49 when an anomalous intraventricular hypertrophic band was resected. The first 2D and Doppler echocardiogram after operation disclosed a previously unrecognised intraventricular septal defect. Three years after operation the patient is asymptomatic. PMID- 8200499 TI - [Angiotensin converting enzyme inhibitors during acute phase of myocardial infarct]. AB - Up to September, 1993, several questions were open on the use of angiotensin converting enzyme (ACE) inhibitors after myocardial infarction. The SAVE trial has shown that patients with left ventricular dysfunction and a recent (mean 11 days) myocardial infarction benefit from assuming captopril per os during the subsequent clinical course. The SOLVD trials have indicated that therapy with enalapril per os increases the survival of patients with left ventricular dysfunction, a history of myocardial infarction and hemodynamic decompensation. However, the CONSENSUS II trial has not shown similar results on patients with all range left ventricular function, treated within 24 hours of infarction with i.v. enalaprilat and then enalapril per os. In this study, 6-month mortality has been slightly better in the placebo group, and there seems not to be any subgroup benefitting from the ACE inhibitor. In October and November, 1993, the International Cardiologic Community has received the results of 3 large multicenter trials on postinfarction patients: the AIRE (ramipril per os), the GISSI 3 (lisinopril per os) and the ISIS 4 (captopril per os) studies. These trials has pointed out the followings: 1) prompt therapy (within 24 hours of chest pain) with ACE inhibitors is able to improve short term survival in patients with clinical evidence of heart failure, in women and old patients; 2) ACE inhibitors and nitro derivatives are complementary therapies in the acute and subacute phase of infarction, and their association produces the best improvement in short-term survival. There seems to be no intelligible reason, up to now, to deem that any ACE inhibitor should be considered better than another one in the acute phase of infarction, but still during the first 72 hours after the onset of chest pain the advantages have been shown only with lisinopril and captopril. The negative results of the CONSENSUS II trial are probably dependent on the excessively abrupt acute hypotensive effect of i.v. enalaprilat. This last "large trial" decade has taught us that many treatments can be advantageous for acute myocardial infarction but, apart from thrombolysis, all other medical therapies should not be given extensively, but to peculiar patients carefully selected on clinical grounds. Guidelines from official consensus conferences are expected now, to segregate different patterns of clinical presentations to be treated differently. PMID- 8200500 TI - [The discreet fascination of chaos]. PMID- 8200501 TI - Common nitrogen control of caesium uptake, caesium toxicity and ammonium (methylammonium) uptake in the cyanobacterium Nostoc muscorum. AB - Studies were carried out to examine the role of ammonium transport activity in the control of caesium uptake and toxicity in Nostoc muscorum. The results showed a definite specific role of the ammonium-repressible/derepressible ammonium transport system of the cyanobacterium in caesium uptake, accumulation and toxicity. Furthermore, the results showed that N. muscorum can acquire resistance against diazotrophically-associated caesium toxicity when supplied with ammonium as a nitrogen source. In addition, alternatively, a mutant strain was Cs resistant in the absence of any effect on NH(+4)-transport, suggesting that Cs+ resistance may be determined at more than one cellular site. PMID- 8200502 TI - Establishment of hydrogen-utilizing bacteria in the rumen of the newborn lamb. AB - The development of hydrogenotrophic bacteria in the rumen of lambs was investigated by culture and labeling experiments. 14CO2 and 13CO2 incorporation by the rumen microflora of a 24-h-old lamb showed that while there was no labeled methane, double-labeled acetate was formed indicating the presence of hydrogen dependent acetogenesis. In vitro counts from rumen fluid of 20-h-old lambs confirmed an extensive colonization of acetogenic bacteria while methanogens were absent. Methanogens appeared in the rumen of 30-h-old lambs, and as they developed there was a proportional decrease in the numbers of acetogens, indicating a competition for hydrogen between these two groups. Hydrogen utilizing sulfate-reducing bacteria, which were established by the 3rd day after birth, did not seem to be affected by this competition. PMID- 8200503 TI - Self-assembly of human papillomavirus type 16 capsids by expression of the L1 protein in insect cells. AB - The L1 major protein of human papillomavirus type 16 was expressed in Sf-21 insect cells with a recombinant baculovirus vector. Virus-like particles similar in appearance to empty virions were identified by electron microscopy at densities of 1.29-1.30. Purified particles reacted with monoclonal anti-HPV-16-L1 antibody in Western blot and immuno dot blot suggesting that conformational epitopes are present in the recombinant particles. Immunodot blot assays using human sera correlated with the detection of HPV-16 DNA by the polymerase chain reaction. The results suggest that HPV-16-L1 virions produced by the baculovirus system might be useful for developing serologic tests to measure antibodies to conformational epitopes and may offer potential for vaccine development. PMID- 8200504 TI - Cloning, nucleotide sequence and expression of a hemolysin gene of Clostridium septicum. AB - A genomic library of Clostridium septicum NCTC547 strain was made in Escherichia coli by means of lambda gt10. The DNA insert of a hemolysin-positive (Hly+) lambda-clone was transferred into pUC19. The resulting plasmid, pCS21, confers a Hly+ phenotype on E. coli. Crude lysates of E. coli (pCS21) possessed a strong lytic activity on human erythrocytes and also a lethal effect on mice, characteristic of an alpha toxin. Nucleotide sequence analysis revealed that the insert DNA (5.2 kb) in pCS21 included at least one open reading frame of 1380 bp. The coding frame for hemolysin was predicted to be 1329 bp in size and to encode a protein of 49.8 kDa. It coincided with the molecular mass (48 kDa) of the alpha toxin secreted by C. septicum. Taken together, the data indicated that plasmid pCS21 indeed encoded an alpha toxin gene of C. septicum. PMID- 8200505 TI - RasG protein accumulation occurs just prior to amoebae emergence during spore germination in Dictyostelium discoideum. AB - RasG protein levels in dormant and germinating spores of Dictyostelium discoideum strains JC1 and SG1 were estimated by Western blotting. RasG levels were very low in dormant spores and remained low during the lag period, regardless of whether spores were heat activated or treated with autoactivator during the early stages of spore germination. RasG levels increased late during spore swelling just prior to the emergence stage of germination. These data are consistent with a requirement for RasG during vegetative growth. PMID- 8200506 TI - Several compartments of Saccharomyces cerevisiae are equipped with Ca(2+) ATPase(s) AB - Sucrose density fractionation of yeast membranes revealed two major and two minor peaks of 45Ca2+ transport activity which all co-migrate with marker enzymes of the endoplasmic reticulum, Golgi and membranes associated with these compartments as well as with ATPase activity measured when all other known ATPase are inhibited. Co-migration of 45Ca2+ transport and ATPase activities was also found after removal of plasma membranes by concanavalin A treatment. SDS-PAGE at pH 6.3 shows the Ca(2+)-dependent formation of acyl phosphate polypeptides of about 110 and 200 kDa. It is concluded that several compartments or sub-compartments of yeast are equipped with Ca(2+)-ATPase(s). It is proposed that these compartments are derived from the protein secretory apparatus of yeast. PMID- 8200507 TI - The significance of enteroaggregative Escherichia coli in the etiology of hospitalized diarrhoea in Calcutta, India and the demonstration of a new honey combed pattern of aggregative adherence. AB - Previous studies have identified enteroadherent Escherichia coli that exhibit localized adherence, diffuse adherence and atypical diffuse adherence as diarrhoeagenic agents associated with infantile diarrhoea in Calcutta, India. In this study, a DNA probe specific for enteroaggregative adherence was used to determine the etiological significance of enteroaggregative E. coli in the causation of diarrhoea. From a total of 330 strains of E. coli recovered from 159 cases of acute secretory diarrhoea and 174 cases of invasive diarrhoea, 20 strains hybridized with the probe, whereas of the 25 E. coli strains recovered from 25 healthy controls only 1 strain hybridized with the probe. Of the 21 probe positive strains, 19 adhered to HeLa cells in the typical stacked-brick pattern while 2 strains recovered from 2 cases of secretory diarrhoea adhered to the glass surface in a hitherto undescribed formation which we have termed, based on the appearance, as the honey-comb pattern. The enteroaggregative E. coli strains identified in this study did not produce any conventional enterotoxins and were significantly associated with patients with secretory diarrhoea (10.7%) than with invasive diarrhoea (1.7%). The results of this study indicate that enteroaggregative E. coli play a causal role in acute secretory diarrhoea in this part of the world which lends credence to the involvement of a potent toxin in the pathogenesis of EAggEC mediated infections. PMID- 8200508 TI - Escherichia coli ferric uptake regulator (Fur) can mediate regulation of a pseudomonad iron-regulated promoter. AB - Introduction of a Pseudomonas iron-regulated promoter lacZ fusion (SP1) and a Pseudomonas transcriptional factor into Escherichia coli allowed expression of the promoter in this heterologous host. Evaluation of this promoter in wild-type and fur mutants of E. coli, by measuring beta-galactosidase activity, indicated that E. coli Fur can regulate the Pseudomonas promoter in response to iron starvation. Gel retardation assays suggested that purified Fur protein could interact with the SP1 promoter upstream of the transcriptional start. DNase I footprinting analysis established that Fur protected a primary 58-bp region (-50 to -106 bp). These protein/DNA interactions correlate with the observed in vivo regulation of the SP1 promoter in E. coli and indicate that Fur can functionally regulate a Pseudomonas iron-regulated promoter. PMID- 8200509 TI - Val-237 for Ala substitution in the TEM-2 beta-lactamase dramatically alters the catalytic efficiencies towards carbenicillin and ticarcillin. AB - The mutant 554 of TEM-2 beta-lactamase was selected for a decrease in the resistance to carbenicillin of an Escherichia coli K12 carrier. The amino acid sequence of the mutant beta-lactamase was determined by manual Edman degradation analysis of proteolytic peptides. A single substitution Val for Ala was localized at position 237. The mutant exhibited only 2% of the catalytic efficiency of the wild-type enzyme towards carbenicillin and ticarcillin, whereas it retained 30 60% of the hydrolytic activity towards other penicillin and cephalosporin substrates. Carfecillin, the phenyl ester of the side-chain carboxyl group of carbenicillin, was hydrolysed as a good substrate. This suggests that the behaviour of the mutant enzyme towards carbenicillin may result from ionic rather than steric constraints. A molecular model of the Val-237 TEM-2 mutant suggests possible electrostatic interaction between Glu-171 and the carboxylic group of the side chain of carbenicillin. PMID- 8200510 TI - Phylogeny of human intestinal spirochaetes inferred from 16S rDNA sequence comparisons. AB - The sequence of 1383 nucleotides of the DNA encoding 16S rDNA was determined for strains of human intestinal spirochaetes, comprising an unnamed isolate and "Brachyspira aalborgi" NCTC 11492. A phylogenetic tree was inferred from aligned sequence comparisons between the intestinal spirochaetes, representatives of the Spirochaetales and Escherichia coli. The type strain of Brachyspira aalborgi, though related to the Serpulina spp. at approx. 96.5% sequence similarity was distinct and separated from the unnamed human intestinal isolate, HIS Oman, N26. The latter formed a separated and novel lineage that bisected the Spirochaetales. PMID- 8200512 TI - Haldane's rule and heterogametic female and male sterility in the mouse. AB - Failed genetic experiments or experiments designed for other purposes sometimes reveal novel genetic information. The interspecific cross between laboratory strain mice of the Mus musculus musculus/domesticus complex and the separate species M. spretus is known to produce fertile F1 females and sterile F1 males. Infertility of the interspecific F1 XY male is said to be an example of what has become known as Haldane's rule: "When in the F1 offspring of two different animal races one sex is absent, rare, or sterile, that sex is the heterozygous [heterogametic] sex." We attempted to use fertile single-X (or XO) female laboratory mice of the M. m. musculus/domesticus complex mated to M. spretus males to construct females with specific X chromosomes to study segregation distortion of X chromosome marker genes that we reported previously in crosses with the two species. We assumed that the interspecific F1 XO female would be fertile like the interspecific F1 XX female but, instead, we found that it is infertile. Haldane's rule is not specific to sex, but demonstration of this has required study of separate species pairs with heterogametic males or with heterogametic females. The fertile XO laboratory mouse is female, but it is also heterogametic, producing both X and nullo-X eggs. Infertility of both the interspecific and heterogametic F1 XO female and F1 XY male in the same cross between laboratory mice and M. spretus suggests that heterogamety is at the cause of the infertility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200511 TI - Three spontaneous mutations at the albino locus in SELH/Bc mice. AB - The SELH/Bc inbred mouse stock has produced an unusually high number of spontaneous mutations, including sph2Bc, nuBc, a recessive lens opacity, and three mutations at the c locus. Classical genetic and molecular genetic studies were done to investigate the origin of the albino locus mutations. Southern blots probed with the mouse tyrosinase cDNA showed that two of the mutations, cBc and c2Bc, are deletions of exons 1, 2 and 3. The third mutation, c3Bc, showed a disruption, either a rearrangement or an insertion, in the region of exon 1. The deletion of the cBc mutation is anticipated to be large as the mutation has inactivated the Mod-2 locus 2 cM away, and an essential locus for post implantation survival outside the c-Mod-2 interval, whereas the c2Bc mutation is viable and fertile in homozygotes. Homozygotes for c3Bc are also viable and fertile. We conclude that at least some of the molecular events leading to the three albino mutations were independent. The mutations differ from each other and from the classical albino point mutation. All three new mutations originated from parents who were germline mosaics, and the mutational events were therefore all postmeiotic. All three mosaics shared one common ancestor six generations previously, raising the possibility that an instability of the albino locus might have been inherited. SELH/Bc mice may provide an animal model for the study of mechanisms underlying genetic instability. PMID- 8200513 TI - Influence of nuclear background on transcription of a chimeric gene (orf256) and coxI in fertile and cytoplasmic male sterile wheats. AB - Crosses between Triticum timopheevi, as maternal donor, and T. aestivum can lead to cytoplasmic male sterile (cms) plants. The T. timopheevi derived mitochondrial DNA from parental, cms, and fertility-restored lines differs from that of T. aestivum derived mtDNA in the coxI gene region. Our previous results for cms lines showed that there is an open reading frame, orf256, upstream from coxI in T. timopheevi derived mtDNA that is not present in T. aestivum DNA. The 5' flanking region and the first 33 nucleotides of the coding region of orf256 are identical to the corresponding region of T. aestivum coxI, whereas the rest of orf256, including the 3' flank, is not related to coxI. Also, the organization of orf256 and coxI on a HindIII fragment from T. timopheevi derived mtDNA are identical in T. timopheevi, cms, and fertility-restored lines. We now report that the DNA sequence of orf256 is identical in T. timopheevi, cms, and fertility restored lines. Major transcripts in cms and fertility-restored lines encode both orf256 and coxI with 5' termini like coxI mRNA of T. aestivum, whereas parental mitochondria from T. timopheevi have major transcripts with 5' termini within the orf256 coding region. Mitochondria from cms and fertility-restored lines have the potential to produce a protein that would not be present in parental T. timopheevi or in T. aestivum. PMID- 8200514 TI - Resolution of populations of the Mediterranean fruit fly at the DNA level using random primers for the polymerase chain reaction. AB - We have used the polymerase chain reaction (PCR) and the random amplified polymorphic DNA (RAPD) method to identify DNA polymorphisms that can be used as genetic markers to characterize populations of the Mediterranean fruit fly, Ceratitis capitata. In this study, RAPD markers have been used to resolve genetic variability between populations of this major agricultural pest species. The populations analyzed represent either laboratory stocks or wild collections originating from different geographic localities. Using the same set of individual flies from each of several populations, we show that the use of different primers in the RAPD method permits detection of different levels of population differentiation. We show results from RAPD primers (e.g., primer 14) that identify regions of the genome (through PCR amplification) that are essentially monomorphic in all flies originating from a particular geographic locality. We also show RAPD primers (e.g., primer 67) that identify what appear to be highly variable regions of the genome. We have used primers of this type to produce genetic markers that can distinguish even between laboratory versus wild populations as well as subpopulations of flies from more broadly defined geographic localities, such as within the Hawaiian islands. These results show that the RAPD method is a broadly applicable, high resolution method for documenting genetic variability within and between populations of insect pest species. PMID- 8200515 TI - New mutations that suppress mating-type vegetative incompatibility in Neurospora crassa. AB - The mating-type locus in the ascomycete Neurospora crassa functions as a vegetative-incompatibility locus during asexual growth such that A+a heterokaryons and A/a partial diploids are inhibited in their growth. In this study, we sought mutations that suppress mating-type associated vegetative incompatibility by using A/a partial diploids. Mutants were selected as spontaneous escapes from inhibited growth. Suppressors were identified by selecting escapes that retained the capacity to mate with both A and a strains. The escaped partial diploids were then outcrossed to remove the duplication. Seven suppressors were identified that segregated as single, recessive mutations. All seven of the suppressors were shown to be allelic to a previously obtained suppressor, tol, by segregation analyses and heterokaryon tests. This result indicates that all seven mutations are new alleles of tol and suggests that tol is a key regulatory locus in the expression of mating-type associated vegetative incompatibility in N. crassa. PMID- 8200516 TI - Characterization of a translocation and its impact on fertility in the pig. AB - A chromosome anomaly originally detected in two intersex pigs and previously reported as a Robertsonian translocation was characterized, and its transmission pattern was assessed by analyzing the progeny and immediate relatives of a sow. Cytogenetic investigations on four phenotypically normal relatives of the intersexes, including a sow, showed that the rearrangement was a reciprocal translocation involving the X chromosome and an autosome. Giemsa-banding and reverse-banding techniques indicated that the break in the X chromosome may have occurred in the terminal segment of the short arm (Xp) and that in the autosome in the proximal segment of the acrocentric chromosome 14 (14q). Reverse-banding techniques also revealed that the normal X is the late-replicating X in female translocation carriers. Centromere banding revealed an intercalary band on the long arm of the submetacentric chromosome representing the altered X in translocation carriers. The translocation was designated as rcp (X;14) (p+;q-). Chromosome analysis on 45 of 72 live offspring of the carrier sow showed a 20:25 distribution of carriers to normal piglets, with a carrier to normal ratio of 5:13 among females and 15:12 among male piglets, indicating an overall reduction of females (18) compared with males (27). Male carriers from one litter at sexual maturity showed hypoplastic testes and no spermatozoa in their ejaculates or fluid aspirates from the cauda epididymis. Their seminiferous tubules were narrow, spermatogenesis was impaired, and pyknotic and giant nuclei were abundant in the germinal epithelium. Meiotic preparations showed no stage beyond pachytene, suggesting that the absence of spermatozoa in the ejaculates may be due to the arrest of cells at the pachytene stage. PMID- 8200517 TI - Genetic variability and segregation analysis in Glossina moristans moristans (Diptera: Glossinidae) using DNA fingerprinting. AB - DNA hybridization, using the M13 sequence as a probe, was used to analyze the genetic variability in four inbred lines of the tsetse fly Glossina morsitans morsitans Westwood. An average of 11.2 bands (ranging from 2 to 10 kb) were found per fly. An average of nine loci were detected in each line; 40% of the loci were polymorphic and the mean heterozygosity per locus varied from 0.098 to 0.29. Averaging the data across the four inbred lines, the band sharing estimates were 82.5% in males and 81.2% in females, and the mean band frequency estimates were 0.71 and 0.70 for males and females, respectively. Segregation of fragments, determined in "three generation" pedigrees, conformed to expected Mendelian ratios and two of seven fragments studied were linked to an X chromosome marker gene, ocra (body color). PMID- 8200518 TI - The testis-determining autosomal trait, Tda-1, of C57BL/6J is determined by more than a single autosomal gene when compared with DBA/2J mice. AB - The putative Tda-1 or testis-determining autosomal trait of the C57BL/6J mouse strain came to attention when the Y chromosome from the poschiavinus variety of Mus musculus domesticus was introduced into C57BL/6J by backcross matings. The F1 generation expressed normal testis development in XY individuals with the poschiavinus Y chromosome. In the backcross and subsequent crosses to C57BL/6J females, XY individuals expressed ovaries bilaterally or various combinations of an ovotestis with a contralateral ovary or testis or bilateral ovotestes and a few had testes bilaterally. Some of the previous breeding data appeared to support the hypothesis that C57BL/6J had an autosomal recessive factor that differed from the poschiavinus strain and, in the homozygous state, caused incomplete testis development with the poschiavinus Y chromosome. Subsequent attempts to map the Tda-1 factor, using a recombinant inbred strain approach, failed to localize Tda-1 and this suggests it might map to different chromosomes depending on which strain pairs are used. We constructed two strains of C57BL/6J and DBA/2J that are congenic for the poschiavinus Y chromsome. In the C57BL/6J. Y POS congenic strain, liability to express incomplete testis development is normally distributed and thresholds in development specify the probability (or areas under the normal distribution) of different classes of ovary, ovotestis, and testis combinations. Testis development is normal in the DBA/2J. Y-POS congenic strain. With the two congenic strains and their normal parental strains we were able to conduct standard crosses to examine the reciprocal F1 and four types of backcross generations to the C57BL/6J strain in which all XY individuals have the poschiavinus Y chromosome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200519 TI - Amplification of DNA sequences in wheat and its relatives: the Dgas44 and R350 families of repetitive sequences. AB - The sequence of a Triticum tauschii genomic clone representing a family of D genome amplified DNA sequences, designated Dgas44, is reported. The Dgas44 sequence occurs on all chromosomes of the D genome of wheat, Triticum aestivum, and in situ hybridization revealed it to be evenly dispersed on all seven chromosome pairs. An internal HindIII fragment of Dgas44, designated Dgas44-3, defines the highly amplified region that is specific to the D genome. The polymerase chain reaction was used to amplify a 236-bp fragment within Dgas44-3 from chromosomes 1D, 2D, 3D, 4D, 5D, and 7D, and identical copies of this region of the Dgas44-3 sequence were found among the isolates from each of the chromosomes. The Dgas44-3 sequence population from specific chromosomes differed on average by 0.22% from the original Dgas44 sequence. The Dgas44 sequence was found to differentiate between the D genome present in T. aestivum, T. tauschii, hexaploid T. crassum, T. cylindricum, T. ventricosum, in which the sequence was present in a highly amplified form and T. juvenale, T. syriacum, and tetraploid T. crassum where the sequence family was difficult to detect. Another class of amplified sequences previously considered to be rye "specific." R350, was isolated from tetraploid wheat and its dispersed distribution on chromosomes was similar to the Dgas44 family in T. tauschii. In contrast with the Dgas44 sequence family, genome specificity for the remnant R350 sequence family was not evident since it was present on all wheat chromosomes. PMID- 8200520 TI - The use of RAPD for identifying and classifying Musa germplasm. AB - Using the technique of random amplified polymorphic DNA (RAPD), we have identified 116 amplification products in Musa germplasm using nine primers. This has enabled us to identify RAPD markers that are specific to each of nine genotypes of Musa representing AA, AAA, AAB, ABB, and BB genomes. The pattern of variation observed following the application of multivariate analyses to the RAPDs banding data is very similar to the pattern of variation defined using morphological characters and used to assign Musa material into the different genome classes. PMID- 8200521 TI - Mutation at VNTRs: Are minisatellites the evolutionary progeny of microsatellites? PMID- 8200522 TI - The dam and dcm strains of Escherichia coli--a review. AB - The construction of a variety of strains deficient in the methylation of adenine and cytosine residues in DNA by the methyltransferases (MTases) Dam and Dcm has allowed the study of the role of these enzymes in the biology of Escherichia coli. Dam methylation has been shown to play a role in coordinating DNA replication initiation, DNA mismatch repair and the regulation of expression of some genes. The regulation of expression of dam has been found to be complex and influenced by five promoters. A role for Dcm methylation in the cell remains elusive and dcm- cells have no obvious phenotype. dam- and dcm- strains have a range of uses in molecular biology and bacterial genetics, including preparation of DNA for restriction by some restriction endonucleases, for transformation into other bacterial species, nucleotide sequencing and site-directed mutagenesis. A variety of assays are available for rapid detection of both the Dam and Dcm phenotypes. A number of restriction systems in E. coli have been described which recognise foreign DNA methylation, but ignore Dam and Dcm methylation. Here, we describe the most commonly used mutant alleles of dam and dcm and the characteristics of a variety of the strains that carry these genes. A description of several plasmids that carry dam gene constructs is also included. PMID- 8200523 TI - The Streptomyces aureofaciens homologue of the whiG gene encoding a putative sigma factor essential for sporulation. AB - A putative sigma factor-encoding gene, rpoZ, was cloned from Streptomyces aureofaciens. Its deduced protein product showed high similarity to the putative sigma factor encoded by the Streptomyces coelicolor whiG gene. Disruption of rpoZ blocked differentiation at a stage between the formation of aerial mycelium and the development of mature spores. PMID- 8200524 TI - Homology between Borrelia burgdorferi OspC and members of the family of Borrelia hermsii variable major proteins. AB - Synthesis of the Borrelia burgdorferi outer surface protein C (OspC) is quite variable. We have cloned and sequenced the ospC gene from B. burgdorferi isolate CA-11.2A, a clone in which ospC expression varies. The 5' flanking region of the gene contains at least two consensus promoter regions, as well as two large overlapping inverted repeats. Sequence comparison to other OspC proteins indicated that the CA-11.2A OspC is as closely related to OspC from two different genospecies of Lyme disease spirochetes as it is to OspC from the prototype B. burgdorferi strain, B31. Comparisons of the OspC amino acid (aa) sequence with those in aa sequence databases revealed partial identity with the variable major proteins Vmp3 and Vmp24 of B. hermsii, a causative agent of tick-borne relapsing fever. An ospC probe hybridized to B. hermsii restriction fragments and linear plasmids that also were recognized by the vmp3 and vmp24 probes. OspC and these Vmp appear to be related, but their synthesis is regulated differently in the two species of spirochetes. This represents a fascinating example of the evolution of the number, position, regulation and perhaps function of homologous genes in two related pathogens. These parameters may relate to characteristic properties of the pathogens and their separate tick vectors. PMID- 8200525 TI - Cloning and sequencing of the Legionella pneumophila fur gene. AB - Iron is required for the intracellular and extracellular growth of Legionella pneumophila (Lp). In addition, variations in iron levels may serve as a signal for changes in gene expression. In a number of bacterial pathogens, the regulation of gene expression by iron is usually mediated by the Fur (ferric uptake regulation) repressor protein. Through complementation of an Escherichia coli fur mutation and nucleotide sequence analysis, we have cloned and characterized the Lp fur gene. Lp fur encoded a 15.0-kDa protein whose repressive activity was, as expected, highest in bacteria grown in iron-rich media. Computer analysis determined that Lp Fur had an amino-acid identity of over 54% and a similarity of over 72% to the Fur of E. coli, Yersinia pestis, Vibrio species and Pseudomonas aeruginosa. The promoter region of Lp fur contained sequences homologous to the Fur-binding site, suggesting that fur is autoregulated in Lp. Finally, Southern blot hybridizations demonstrated that fur is conserved among Lp strains and Legionella species. PMID- 8200526 TI - Cloning and characterization of the gene encoding the major sigma factor of Stigmatella aurantiaca. AB - The gene (sigA) encoding the major sigma factor of the myxobacterium, Stigmatella aurantiaca, was cloned and sequenced. The deduced polypeptide contains 706 amino acids (aa) and has a deduced M(r) of 79,910. It exhibits four different aa sequence motifs which correlate with the conserved domains of the major sigma factors of Myxococcus xanthus (sigma 80), Escherichia coli (sigma 70) and Bacillus subtilis (sigma 43). The sigma factor (sigma A) was detected in crude lysates of vegetative cells and in cells of different developmental stages from S. aurantiaca with an antiserum to M. xanthus sigma 80 by Western blot analysis. The SigA polypeptide copurified with RNA polymerase from vegetative S. aurantiaca cells. The aa sequence of its N terminus matches a sequence located 25 codons downstream from the proposed start codon. The sigA gene was expressed in E. coli and the corresponding gene product cross-reacted with the SigA antiserum as a polypeptide of 100 kDa, which is identical in size to the sigma A detected in vegetative cells of S. aurantiaca. PMID- 8200528 TI - High-level expression of the phenylalanine ammonia lyase-encoding gene from Rhodosporidium toruloides in Saccharomyces cerevisiae and Escherichia coli using a bifunctional expression system. AB - A chimeric yeast promoter (pPGK::REP2), capable of directing high-level gene expression in both Saccharomyces cerevisiae and Escherichia coli, has been constructed. It was derived by fusing the promoter of the yeast PGK gene (encoding phosphoglycerate kinase) to a region residing immediately 5' to the yeast 2 mu plasmid REP2 gene (encoding a trans-acting plasmid maintenance protein). In S. cerevisiae, transcripts initiated within the REP2-derived moiety of the promoter, but the transcription start point was dictated by the PGK determinator sequence. Promoter function in E. coli was due to the presence of consensus prokaryotic -35 and -10 motifs in the REP2 moiety. To facilitate expression studies, the promoter was incorporated into a versatile series of S. cerevisiae/E. coli shuttle vectors which provided a choice of selectable marker and copy number in S. cerevisiae. To maximise translational efficiency, a novel cloning strategy was devised which allows the juxtaposition of genes to the promoter such that the heterologous AUG replaces that of the REP2 AUG, without any alteration in the surrounding nucleotide (nt) context. This strategy was used to place both the Tn903 neo gene and the Rhodosporidium toruloides phenylalanine ammonia lyase (PAL)-encoding gene under the transcriptional control of pPGK::REP2. In the former case, cells became resistant to extremely high levels of Geneticin (> 3 mg/ml in the case of S. cerevisiae). In the case of the latter, PAL was shown to accumulate to approx. 9 and 10% of total soluble protein in S. cerevisiae and E. coli, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200527 TI - Cloning and chromosomal organization of a gene encoding a putative amino-acid permease from Saccharomyces cerevisiae. AB - A new member of the yeast amino acid (aa) permease gene family has been cloned, mapped and sequenced. The sequence of the PAP1 (putative aa permease 1) gene contains an open reading frame of 566 aa corresponding to a polypeptide with a calculated M(r) of 62,704. Its hydropathy profile suggests the presence of 13 membrane-spanning regions and a charged N-terminal domain. It does not resemble hydrophobic signal sequences found in secreted proteins. Hence, PAP1 encodes a protein with characteristics typical of integral membrane proteins translocating ligands across cellular membranes. Sequence comparisons indicate strong homology to the five known aa permeases of Saccharomyces cerevisiae and to an aa transporter in Trichoderma harzianum. Primer extension analysis revealed one major and one minor transcription start point located 121 and 125 nucleotides upstream from the ATG start codon, corresponding to a 2.1-kb transcript. PAP1 was mapped in a contig of three known (DBF4, TPI and HEM12), but so far unlinked, genes on chromosome IV. PMID- 8200529 TI - The MCS1/SSD1/SRK1/SSL1 gene is involved in stable maintenance of the chromosome in yeast. AB - A temperature-sensitive (ts) mutant of Saccharomyces cerevisiae was isolated in which mini-chromosomes were unstable at high temperature. The MCS1 gene (Mini Chromosome Stability 1) was cloned by the ability of complementing the temperature sensitivity, and was found to be identical to SSD1/SRK1/SSL1. When MCS1/SSD1 was disrupted in a certain wild-type (wt) strain, mini-chromosomes were unstable, even at 30 degrees C, indicating that the gene is involved in chromosome stability. The Mcs1/Ssd1 protein was detected as a 170-kDa protein by immuno-blotting analysis and this 170-kDa protein could not be detected in the ts mutant and certain wt strains. Our results are consistent with the genetic data that there are two polymorphic forms of the gene, SSD1-v and ssd1-d [Sutton et al., Mol. Cell. Biol. 11 (1991) 2133-2148]. Furthermore, genetic backgrounds other than MCS1/SSD1 caused strain-specific phenotype. The protein, precipitated by specific antibodies, was phosphorylated. PMID- 8200530 TI - Switching gene swi6, involved in repression of silent mating-type loci in fission yeast, encodes a homologue of chromatin-associated proteins from Drosophila and mammals. AB - The switching gene swi6 of Schizosaccharomyces pombe is involved in the repression of the silent mating-type loci mat2 and mat3. We have cloned the gene by functional complementation of the switching defect of the swi6-115 mutation. DNA sequence analyses revealed an open reading frame of 984 bp coding for a putative protein of 328 amino acids (aa). The isolation of a swi6 cDNA confirmed this result. Gene replacement showed that swi6 is not essential for viability. The Swi6 protein is very hydrophilic; it contains 41% charged aa. A region of 48 aa is homologous to a sequence motif found in the chromatin-associated proteins, HP1 and Polycomb (Drosophila melanogaster), M31, M32 and M33 (mouse), and the human HSM1 protein. This motif is called chromo domain (chromatin organization modifier). Our results indicate that Swi6 is a structural component of chromatin. Swi6 may have the function to compact mat2 and mat3 into a heterochromatin-like conformation which represses the transcription of these silent cassettes. PMID- 8200531 TI - Generalized and mobilizable positive-selection cloning vectors. AB - We have modified the positive-selection cloning vector pUN121 to expand the numbers of unique cloning sites by insertion of a multiple cloning site into the lambda cI gene without disrupting its repressor function, resulting in plasmid pSKM10. Plasmid pSKM10 has seven restriction enzyme sites suitable for general cloning purposes. A mobilizable version (pSKM11) of pSKM10 was constructed by insertion of the IncP mob sequence which permitted mobilization of the plasmid into a wide variety of Gram- bacteria. PMID- 8200532 TI - Sequences of ccpA and two downstream Bacillus megaterium genes with homology to the motAB operon from Bacillus subtilis. AB - A regulatory gene with 69% nucleotide sequence identity to the Bacillus subtilis ccpA was cloned from Bacillus megaterium by complementation of a mutant relieved of catabolite repression. Sequencing of the gene and its adjacent regions revealed two additional open reading frames (ORFs) downstream from ccpA. These three genes are presumably in one operon. ORF1 and ORF2 show homology to two genes downstream from ccpA in B. subtilis, as well as to the B. subtilis motA and motB genes, respectively. PMID- 8200533 TI - Direct cloning of unmodified PCR products by exploiting an engineered restriction site. AB - A method is described for the direct cloning of DNA fragments amplified by the polymerase chain reaction (PCR). An oligodeoxyribonucleotide, bearing two engineered XcmI sites placed in tandem, was used to generate cloning vectors bearing single 3' deoxythymidine (dT) overhangs at their ends. These 3' dT overhangs are compatible with the 3' deoxyadenosine overhangs found on most Taq polymerase-amplified PCR products. Consequently, Taq polymerase-amplified PCR products can be ligated directly into these modified restriction sites. PMID- 8200534 TI - Genetic and biochemical evidence for yeast GCN2 protein kinase polymerization. AB - The GCN2 (general control kinase 2) protein is an eIF2-alpha (eukaryotic initiation factor alpha) kinase which mediates translational derepression of the yeast general control transcriptional activator, GCN4, upon amino-acid starvation. We isolated and characterized GCN2 mutations differentially affecting GCN2 function. Mutations mapping in, or close to, the ATP-binding site of the kinase moiety result in constitutively activated GCN2 molecules. A C-terminal regulatory mutation dramatically affects translation initiation rates resulting in pleiotropic phenotypes. The effect of mutations in both regions were found to depend on eIF2-alpha phosphorylation. We have demonstrated that GCN2 mutants have altered autophosphorylation activities in vitro, depending on the presence or absence of a wild-type GCN2 gene and that GCN2 elutes in gel-filtration chromatography fractions with high apparent molecular mass. Both these genetic and biochemical findings suggest that GCN2 functioning might involve polymerization to form dimers or tetramers. PMID- 8200535 TI - Deletion of P9 and stem-loop structures downstream from the catalytic core affects both 5' and 3' splicing activities in a group-I intron. AB - The P9 stem-loop is one of the conserved structural elements found in all group-I introns. Using two deletion mutants in this region of the Tetrahymena thermophilia large ribosomal subunit intron, we show that removal of the P9 element, either alone, or together with the non-conserved downstream P9.1 and P9.2 elements, results in an intron incapable of the first step of the splicing reaction at a low concentration of Mg2+. The mutant introns also require high concentrations of Mg2+ for the second step in splicing, as well as hydrolysis reactions, suggesting that P9, as well as P9.1 and P9.2, are important structural elements in the final folded form of the intron. In addition, RNase-T1-mediated structure-probing experiments demonstrated that the loss of P9, P9.1 and P9.2 changes the structural context of the region binding the 5' splice site. The deletions lead to less efficient recognition of the 3' splice site and an accumulation of unligated exons. These observations support the view that the P9, P9.1 and P9.2 stem-loops play an important role in the binding of the 3' splice site. PMID- 8200536 TI - Restriction mapping of phage lambda vectors using non-radioactive methods. AB - In order to take advantage of non-radioactive methods, we have developed two plasmids (p lambda LE and p lambda RE) for mapping restriction sites of long inserts cloned in phage lambda vectors. These plasmids are constructed by cloning the left 402-bp and right 560-bp phage lambda genome ends, respectively. To map restriction sites, the cloned sequences in p lambda LE and p lambda RE are labeled with digoxygenin and hybridized to partially digested lambda DNA. The ladder of bands detected with these probes can be used to construct restriction maps in the same way as those obtained using radioactively labeled cos complementary oligodeoxyribonucleotides [Rackwitz et al., Gene 30 (1984) 195 200]. PMID- 8200537 TI - CCC.UGA: a new site of ribosomal frameshifting in Escherichia coli. AB - To activate expression of a human transferrin (Tf)-encoding cDNA in Escherichia coli by translational coupling, it was placed in an expression plasmid downstream from a 5'-terminal fragment from the replicase (R)-encoding gene of bacteriophage MS2. The resulting construct was found to produce, besides the desired Tf, a protein with the mobility of a fusion product (RTf) of the N-terminal R fragment and Tf. Analysis of available mutants showed that this fusion results from +1 ribosomal frameshifting at the end of the R reading frame. This region contains the sequence, CCC.UGA, suggesting that before termination occurs, tRNA(Pro) may dislodge from the CCC codon and reassociate with the +1 triplet CCU. By further site-directed mutagenesis, we demonstrate that both the CCC codon and the termination codon are indeed required for the observed 2-4% frameshifting. When either triplet is changed, the frequency of frameshifting drops to 0.3% or less. These results classify CCC.UGA as a new '+1 shifty stop'. PMID- 8200538 TI - Sequence analysis of the flgA gene and its adjacent region in Salmonella typhimurium, and identification of another flagellar gene, flgN. AB - The flagellar genes flgA and flgM are located at the terminus of the region-I flagellar gene cluster on the chromosome of Salmonella typhimurium. The flgA gene is involved in P-ring formation of the flagellar basal body, whereas flgM encodes the anti-sigma factor which acts as a negative regulator of the flagellar regulon. The nucleotide sequence of the DNA fragment containing these flagellar genes and the adjacent region was determined. The flgA gene was found to encode a 219-amino-acid (aa) protein of 23,556 Da. The N-terminal region of FlgA has the characteristics of a typical signal sequence, suggesting that FlgA may function in the periplasmic space where P-ring assembly takes place. The flgM gene was found to constitute an operon together with an ORF which encodes a 140-aa protein of 15,899 Da. A gene disruption mutant was constructed by inserting a cat gene cartridge into the ORF on the chromosome. This mutant showed only weak motility, indicating that the product of the ORF is involved in flagellar formation. Therefore, this ORF was designated as flgN. Electron microscopic observation revealed that most of the flagellar structures produced by the flgN mutant are hook-basal body complexes lacking the filament portions. Based on these results, we concluded that the flgN product is required for the efficient initiation of filament assembly. PMID- 8200539 TI - Alginate lyase from Klebsiella pneumoniae, subsp. aerogenes: gene cloning, sequence analysis and high-level production in Escherichia coli. AB - The alyA gene, encoding a secreted guluronate-specific alginate lyase (Aly) from Klebsiella pneumoniae subsp. aerogenes type 25, has been cloned. DNA sequence analysis reveals two possible translation start sites for the precursor form of Aly and a long open reading frame (ORF) predicted to encode a 287-amino-acid (aa) mature form of Aly, in agreement with N-terminal aa sequence analysis of the protein. Aly has a calculated molecular mass of 31.4 kDa, in good agreement with SDS-PAGE analysis, and a calculated pI of 9.39. Comparison of the deduced aa sequence with a mannuronate-specific lyase from a marine bacterium reveals 19.3% identity and 28.8% similarity with a 9-aa conserved region close to the C terminus, probably of functional or structural significance. There is no obvious sequence similarity with pectate lyases which also catalyse a beta-elimination reaction. Heterologous expression of K. pneumoniae alyA in Escherichia coli yields 10 mg of Aly per litre of culture supernatant, apparently due to non specific release from the periplasm. PMID- 8200540 TI - Recombinant Escherichia coli strains synthesize active forms of naphthalene dioxygenase and its individual alpha and beta subunits. AB - Pseudomonas sp. strain NCIB 9816-4 utilizes naphthalene dioxygenase (NDO), a multicomponent enzyme system, to initiate naphthalene degradation. The terminal component of NDO is an iron-sulfur protein (ISPNAP) with an alpha 2 beta 2 subunit composition. The structural genes encoding the alpha (nahAc) and beta (nahAd) subunits were cloned separately and together into expression vectors where transcription is under the control of the T7 promoter. The recombinant plasmids were transformed into Escherichia coli JM109[pGP1-2] and the synthesis of ISPNAP and its alpha and beta subunits was determined by SDS-PAGE. Low expression of nahAd was shown to be due to inefficient initiation of translation, but a sixfold increase in the amount of beta subunit synthesized was achieved in a coupled translation system. Inclusion bodies were found in all recombinants. Increased levels of soluble active proteins were obtained when E. coli JM109(DE3), used as the host strain for recombinant plasmid, was grown at 25 degrees C. ISPNAP from JM109(DE3)[pDTG121] was purified to homogeneity and shown to have the same properties as those determined for the enzyme purified from NCIB 9816-4. Active ISPNAP was also obtained by mixing cell extracts from separate strains that synthesized the alpha and beta subunits. The availability of large amounts of purified ISPNAP and its alpha and beta subunits will facilitate future studies on the mechanism of oxygen fixation by NDO. PMID- 8200541 TI - Genetic evidence for a fourth terminal oxidase in Bradyrhizobium japonicum. AB - Bradyrhizobium japonicum, a symbiotic nitrogen-fixing bacterium, has a complex respiratory electron-transport chain, capable of functioning throughout a wide range of oxygen tensions. It does so by synthesizing a number of terminal oxidases, each appropriate for different environmental conditions. Several genes encoding terminal oxidases from B. japonicum have been cloned, but it is unknown what roles these individual oxidases play. In this paper, we describe the cloning and sequencing of the coxX gene encoding the large catalytic subunit for a fourth terminal oxidase from B. japonicum. The coxX gene encodes a 666-amino-acid (aa) protein (M(r) 74,527) that exhibits a high degree of homology to terminal oxidase proteins from a number of prokaryotic and eukaryotic species. This new oxidase exhibits greater homology to the Escherichia coli cytochrome o subunit I than any of the previously reported B. japonicum terminal oxidase genes. PMID- 8200542 TI - The penicillin amidase of Arthrobacter viscosus (ATCC 15294). AB - The nucleotide (nt) sequence of the gene encoding penicillin G amidase (PA) of Arthrobacter viscosus strain ATCC 15,294 was determined. The sequence contained an open reading frame of 2406 nt with a G+C content of 37%. The deduced amino acid sequence shows significant homology with other so far identified beta-lactam amidases of Gram- bacteria. PMID- 8200543 TI - Sequences of the cobalamin biosynthetic genes cobK, cobL and cobM from Rhodococcus sp. NI86/21. AB - Sequence analysis of a 5753-bp genomic fragment of Rhodococcus sp. NI86/21 revealed the presence of three homologues of known cobalamin biosynthetic genes. One of these genes encodes a protein showing strong homology with the precorrin 6x reductase (CobK) of Pseudomonas denitrificans. In addition, the rhodococcal homologue of the corrin methyltransferases, CobM from P. denitrificans and CbiF from Salmonella typhimurium, was identified. The protein deduced from a third Rhodococcus gene aligns well with CobL of P. denitrificans and with the protein pair CbiE/CbiT of S. typhimurium, which are involved in corrin methylation and decarboxylation. PMID- 8200544 TI - Structural proteins of mycobacteriophage I3: cloning, expression and sequence analysis of a gene encoding a 70-kDa structural protein. AB - The structural proteins of mycobacteriophage I3 have been analysed by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis (SDS-PAGE), radioiodination and immunoblotting. Based on their abundance the 34- and 70-kDa bands appeared to represent the major structural proteins. Successful cloning and expression of the 70-kDa protein-encoding gene of phage I3 in Escherichia coli and its complete nucleotide sequence determination have been accomplished. A second (partial) open reading frame following the stop codon for the 70-kDa protein was also identified within the cloned fragment. The deduced amino-acid sequence of the 70-kDa protein and the codon usage patterns indicated the preponderance of codons, as predicted from the high G+C content of the genomic DNA of phage I3. PMID- 8200545 TI - Liver cell death: patterns and mechanisms. PMID- 8200546 TI - Persisting diarrhoea and malabsorption. PMID- 8200547 TI - Cancer surveillance in ulcerative colitis--a time for reappraisal. PMID- 8200548 TI - Omeprazole v ranitidine for prevention of relapse in reflux oesophagitis. A controlled double blind trial of their efficacy and safety. AB - The aim of this study was to compare recurrence rates of reflux oesophagitis (after endoscopic healing with omeprazole) over a 12 month period of randomised, double blind, maintenance treatment with either daily omeprazole (20 mg every morning; n = 53), weekend omeprazole (20 mg on three consecutive days a week, n = 55) or daily ranitidine (150 mg twice daily, n = 51). Patients were assessed for relapse by endoscopy (with gastric biopsy) at six and 12 months, or in the event of symptomatic recurrence, and serum gastrin was monitored. At 12 months, the estimated proportions of patients in remission (actuarial life table method) were 89% when receiving daily omeprazole compared with 32% when receiving weekend omeprazole (difference 57%, p < 0.001, 95% confidence intervals: 42% to 71%) and 25% when receiving daily ranitidine (difference 64%, p < 0.001, 95% confidence intervals: 50% to 78%). Median gastrin concentrations increased slightly during the healing phase, but remained within the normal range and did not change during maintenance treatment. No significant pathological findings were noted, and no adverse events were attributable to the study treatments. In conclusion, for patients who respond favourably to acute treatment with omeprazole 20 mg every morning, the drug is a safe and highly effective maintenance treatment for preventing relapse of reflux oesophagitis and its associated symptoms over 12 months. By contrast, weekend omeprazole and daily ranitidine were ineffective. PMID- 8200550 TI - Expression of transforming growth factor alpha in experimental gastric carcinogenesis. AB - The induction of adenocarcinomas in the glandular stomach of the adult male Wistar rat by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was used as a model to study the expression of the growth promoting peptide, transforming growth factor alpha (TGF alpha), during experimental gastric carcinogenesis. TGF alpha was identified using the monoclonal antibody Ab-2 and standard immunohistochemistry, together with a semiquantitative assessment of the intensity of expression. Immunoreactivity was confined to the differentiated compartment of the mucosa while the carcinogen MNNG caused a significant increase in the intensity of TGF alpha expression (p < 0.01), after as little as 16 weeks' exposure. In experimental adenocarcinomas, a change to a previously undescribed pattern of perinuclear TGF alpha expression was found, which may represent the site of intense TGF alpha production in the Golgi apparatus after malignant transformation. PMID- 8200549 TI - Cytochrome P450 expression in oesophageal cancer. AB - The cytochrome P450 superfamily of enzymes play a central part in the metabolism of carcinogens and anti-cancer drugs. The expression, cellular localisation, and distribution of different forms of P450 and the functionally associated enzymes epoxide hydrolase and glutathione S-transferases have been investigated in oesophageal cancer and non-neoplastic oesophageal tissue using immunohistochemistry. Expression of the different enzymes was confined to epithelial cells in both non-neoplastic samples and tumour samples except the CYP3A was also identified in mast cells and glutathione S-transferase pi was present in chronic inflammatory cells. CYP1A was present in a small percentage of non-neoplastic samples but both CYP2C and CYP3A were absent. Epoxide hydrolase was present in half of the non-neoplastic samples and the different classes of glutathione S-transferase were present in a low number of samples. In carcinomas CYP1A, CYP3A, epoxide hydrolase, and glutathione S-transferase pi were expressed in at least 60% of samples. The expression of glutathione S-transferases alpha and mu were significantly less in adenocarcinoma compared with squamous carcinoma. PMID- 8200551 TI - Endoscopic injection therapy for bleeding peptic ulcer; a comparison of adrenaline alone with adrenaline plus ethanolamine oleate. AB - One hundred and seven consecutive patients presenting with significant peptic ulcer haemorrhage were randomised to endoscopic injection with 3-10 ml of 1:100,000 adrenaline (55 patients, group 1) or to a combination of adrenaline and 5% ethanolamine (52 patients, group 2). All had major stigmata of haemorrhage and endoscopic injection was undertaken by a single endoscopist. The groups were well matched with regard to risk factors. Rebleeding occurred in eight of the group 1 patients and seven in the group 2 patients; surgical operation rates, median blood transfusion requirements, and hospital stay were similar in both groups. The efficacy of either form of injection was similar whether patients presented with active bleeding or a non-bleeding visible vessel. No complications occurred. In patients presenting with significant peptic ulcer bleeding, the addition of a sclerosant confers no advantage over injection with adrenaline alone. PMID- 8200552 TI - Increased gastric juice epidermal growth factor after non-steroidal anti inflammatory drug ingestion. AB - Epidermal growth factor (EGF), present in saliva and gastric juice, is a potent mitogen and an important element of mucosal defence. Changes in salivary and gastric juice epidermal growth factor in response to non-steroidal anti inflammatory drug (NSAIDs) ingestion were measured to assess the role of EGF in gastric mucosal adaptation to NSAIDs. Patients with arthritis underwent endoscopy with collection of saliva and gastric juice for EGF measurement, before and two weeks after continuous NSAID ingestion. During this period patients also received either the prostaglandin analogue misoprostol or placebo in addition to their NSAID. In the misoprostol group (n = 5) there was no observed mucosal damage and no change in either salivary or gastric juice EGF. In the placebo group (n = 10) three patients developed erosions. Salivary EGF did not change (mean (SEM) 3.02 (0.54) ng/ml v 2.80 (0.41) ng/ml) but gastric juice EGF increased from 0.42 (0.12) ng/ml to 0.69 (0.14) ng/ml (p < 0.05). This increased EGF could contribute to the increased cellular proliferation observed during NSAID ingestion and may represent an important mechanism underlying gastric mucosal adaptation. PMID- 8200553 TI - Smoking, alcohol, and analgesics in dyspepsia and among dyspepsia subgroups: lack of an association in a community. AB - Dyspepsia is common in the general population, and despite a paucity of data, smoking, alcohol, and analgesics are believed to be important risk factors. The role of these environmental factors in subjects with uninvestigated dyspepsia was evaluated in a representative population sample. An age and gender stratified random sample of residents of Olmsted County, Minnesota, aged 20 to 64 years was mailed a valid self report questionnaire; 77% responded (n = 1644). Age and gender adjusted (1990 US white population) prevalence rates for dyspepsia (defined as frequent pain located in the upper abdomen, or nausea in the absence of a history of peptic ulcer disease) were calculated. Logistic regression analysis was used to estimate the association between dyspepsia and potential risk factors. The age and gender adjusted prevalence (per 100) of dyspepsia in the community was 21.8 (95% confidence interval 19.6, 23.9). Dyspepsia was significantly more common in younger subjects and females. Adjusting for age and gender, paracetamol (odds ratio (OR) = 2.2), aspirin (OR = 1.8), and smoking (OR = 1.5), but not alcohol (OR = 0.9), were associated with dyspepsia (all p < 0.05). When non-gastrointestinal somatic complaints were included in the logistic models, however, these environmental factors were no longer significant (OR = 1.3, 1.1, 1.2 and 0.9, respectively). Similar results were obtained when ulcer like, dysmotility-like, and reflux-like dyspepsia were considered separately. The results were not significantly changed when subjects with a history of ulcer disease were included in the analyses. Smoking, alcohol, and analgesics may not therefore be important risk factors for dyspepsia in the community. PMID- 8200554 TI - Human small intestinal contractions and aboral traction forces during fasting and after feeding. AB - Small intestinal intraluminal pressure activity and aboral traction forces were explored in 19 healthy volunteers using a combined manometry and traction force detecting assembly sited in the upper small intestine. Each aboral traction event was classified as being associated with either a propagating or a stationary contraction and its force measured. During phase I no contractions or traction events were seen. During phase II, traction events related to propagating contractions mean (SEM) (2.2 (0.2)/min) and to stationary contractions (0.3 (0.1)/min) generated similar force/event (7.5(0.9 g v 8.7 (1.4) g, p > 0.05). During phase III, all traction events were related to propagating contractions and generated 9.3 (2.4) g force/event (p > 0.05 v phase II). After feeding, traction events related to propagating contractions generated similar force/event to those related to stationary contractions (5.9 (1.0) g v 9.3 (2.7) g, p > 0.05 v each other and v fasting). No consistent pattern was seen in the temporal distribution of the traction events or in the pattern of the amplitude of the force of successive traction events. PMID- 8200555 TI - Relation between chloride secretion and intracellular cyclic adenosine monophosphate in a cloned human intestinal cell line HT-29 cl 19A. AB - The relation between the intracellular cyclic adenosine monophosphate (cAMP) content and the electrogenic chloride secretion induced by cholera toxin was studied in secretory HT-29 cl 19A cell monolayers. Cells were treated by the mucosal addition of cholera toxin (5 micrograms/ml) for 10, 45, or 90 minutes in Ussing chambers. After 10 minutes, the mean (SEM) intracellular cAMP content (3.2 (0.2) pmol/mg protein) and short circuit current (Isc) (1.9 (0.3) microA.cm-2) did not differ significantly from the corresponding basal values. At 45 minutes, a significant increase in the Isc (22.2 (5.7) microA.cm-2) was accompanied by a significant elevation in cAMP (10(1.7) pmol/mgh protein). At 90 minutes, when the stimulated Isc plateaued (35.2 (5.2) microA.cm-2), the cAMP value (99.2 (23.8) pmol/mg protein) increased further. The protein kinase C (PKC) activity of the cells was not affected by cholera toxin. Treatment of cell monolayers by different concentrations of DbcAMP (10(5), 5 x 10(-5), 10(-3) M) showed that the minimal concentration of DbcAMP (serosal) which significantly increased the Isc (delta 4.5 microA.cm-2) was 10(-4) M, and that this was accompanied by an increase in cAMP of delta 6.7 pmol/mg protein: Compared with DbcAMP, cholera toxin stimulated the Isc (at 45 minutes) to a much higher degree with a comparable elevation of cAMP. It is concluded that in cl 19A cells there is a threshold value of increase in intracellular cAMP that induces chloride secretion. Cholera toxin stimulated chloride secretion can be explained predominantly by an increase in intracellular cAMP that is unrelated to PKC activity. PMID- 8200556 TI - Failure of tropisetron to inhibit jejunal water and electrolyte secretion induced by 5-hydroxytryptamine in healthy volunteers. AB - The effects of the 5-hydroxytryptamine (5-HT3) receptor antagonist, ICS 205-930 (tropisetron), on basal and 5-HT induced jejunal secretion of water and electrolytes were examined using a double blind, randomised crossover design. In seven healthy volunteers steady state perfusions of the proximal jejunum were performed twice with the Loc-I-Gut tube after 5+5 mg ICS 205-930 or placebo capsules were given. After equilibration for 60 minutes and completion of a 120 minute basal period 5-HT (10 micrograms/kg x min intravenously) was infused for 120 minutes. Net water absorption (mean (SEM)) in the basal period was 0.55 (0.84) ml/cm x h and 0.74 (0.72) ml/cm x h after placebo and ICS 205-930, respectively (p > 0.05). Infusion of 5-HT caused significant net secretion of water after placebo (2.05 (0.58) ml/cm x h; p < 0.02) as well as ICS 205-930 (2.60 (0.89) ml/cm x h; p < 0.05). As ICS 205-930 excerted no effects on either basal or 5-HT induced water and electrolyte transport in the intact human jejunum the compound is probably not efficacious as an anti-secretory drug in patients with 5-HT induced diarrhoea. PMID- 8200557 TI - Response of the human intestine to high volume infusion. AB - The motor patterns and luminal capacity of the human intestine should affect symptoms and resorption during pathological, massive small intestinal flow. Little is known of human intestinal motility in this situation. This study aimed at mimicking secretory diarrhoea (experimentally) in healthy volunteers by intrajejunal infusion of a non-absorbable iso-osmotic solution at 20 ml/min. During the infusion intraluminal jejunal pressures and small intestinal transit times were measured. The infusion initially caused jejunal contractile activity similar to that of the fed state but this was replaced by discrete clusters of contractions (DCCs) after 29.1 ((SEM) 8.2) minutes. DCCs each lasted 38 ((SEM) 0.8 seconds) and were associated with colicky abdominal discomfort. Later, after 1400-1800 ml had been infused, distal jejunal pressure waves fell to 10 mm Hg or less. Frequent fasting DCCs predicted earlier onset and more frequent DCCs during the infusion. Thus, the rate and volume of flow during simulated secretory diarrhoea determine the pattern of the small bowel pressure profile; eventually, a volume load is reached in which the small bowel acts as a poorly segmenting conduit resulting in very fast transit rates. PMID- 8200558 TI - Distribution of the carbonic anhydrase isoenzymes I, II, and VI in the human alimentary tract. AB - The distribution of carbonic anhydrase isoenzymes I, II, and VI was studied in the human alimentary tract using specific antibodies to human isoenzymes in conjunction with the immunoperoxidase technique to elucidate the physiological role and possible functional interplay of carbonic anhydrases (CAs) in alimentary canal functions. From the isoenzymes studied, CA II was found to be the most widely distributed in the various epithelia throughout the alimentary canal. In addition to the acinar cells of the parotid and submandibular glands and the duodenal Brunner's glands, it was present in the mucosal epithelium of the oesophagus, stomach, duodenum, and colon. The epithelial cells of the hepatic bile ducts, gall bladder, and pancreatic ducts also contained CA II in abundance. In contrast, CA VI was present only in the serous acinar and ductal cells of the parotid and submandibular glands, and CA I in the mucosal epithelium of the colon and the A cells of the pancreatic Langerhans's islets. These results suggest that CA II as a widely distributed isoenzyme in the epithelia of the alimentary canal and CA VI as secreted into saliva, may form a mutually complementary system protecting oesophageal, gastric, and intestinal mucosa from acidity. PMID- 8200559 TI - Crohn's disease and colorectal cancer. AB - The colorectal cancer risk in Crohn's disease eliminating all known biases was assessed in a cohort of 281 patients with Crohn's disease who resided in the West Midlands at the time of diagnosis, and were first seen within five years of onset of symptoms between 1945-1975. All patients were 15 years of age or more at onset and were followed up from 12-35 years (total 5213 person years at risk (PYR)). The colorectal cancer risk in the series compared with the risk in the general population was computed by applying sex and age specific PYRs to the date of death or end of the study period 31 December 1991. There were six colonic and two rectal cancers. Six of the eight colorectal cancers were diagnosed 20 or more years after the onset of Crohn's disease. The relative risk (RR) of colorectal cancer for the series as a whole was 3.4 (p < 0.001), with a fivefold excess in the colon, but no significant excess in the rectum. Patients with extensive colitis showed an 18-fold increase in risk (RR = 18.2, p < 0.001), which decreased with increasing age at onset. This study shows that there is a statistical excess risk of developing colorectal cancer in patients who develop their Crohn's disease at a young age of onset (less than 30 years of age). PMID- 8200560 TI - Timing of ileocolonic resection for symptomatic Crohn's disease--the patient's view. AB - Eighty patients were asked if they would have preferred their ileocolonic resection and anastomosis for Crohn's disease, to have been carried out sooner, later or at the same time as it was done. Seventy of the patients replied (88%). No patient would have preferred their operation to have been later, while 74% thought it should have been earlier. A preferred operation time was given for 69 resections, between 0 months--that is, at the same time--and 15 years earlier. The median preferred operation time was 12 months earlier (95% confidence intervals 18 months earlier to 7 months earlier). The remaining 18 patients were satisfied with the timing of their operation. Reasons given for earlier surgery in 58 resections included the severity of Crohn's symptoms preoperatively (97%), the ability to eat normally after resection (86%), feeling of well being after the resection (62%), and abolishing the need for drugs (43%). Patients preferring an earlier operation time were less likely to have had a previous resection (13/58) than patients in the 'same time' group (10/21, chi 2 = 4.746; p < 0.05). PMID- 8200561 TI - Pouchitis: result of microbial imbalance? AB - To elucidate the role of microbiological factors in pouchitis, this study investigated the composition of ileal reservoir microflora, the mucus degrading capacity of bacterial enzymes as well as the pH and the proteolytic activity of pouch effluent. Stool samples were collected from five patients with pouchitis and nine patients without pouchitis. The flora of patients with pouchitis had an increased number of aerobes, a decreased ratio anaerobes to aerobes, less bifidobacteria and anaerobic lactobacilli, more Clostridium perfringens, and several species that were not found in control patients (for example, fungi). Furthermore the pH was significantly higher in patients with pouchitis (median value 6.5) than in control patients (5.4). To find out if the pH might influence the breakdown of intestinal mucus glycoproteins, the activity of glycosidases and proteases, and the degradation of hog gastric mucin by the pouch flora was tested at pH 5.2-7.6. Some glycosidases were inhibited, others were stimulated by a low pH, however, in each sample the proteolytic activity was inhibited for 75% at pH 5.2 compared with pH 6.8 and 7.6. Degradation of hog gastric mucin by the pouch flora was an active process at pH 7.2: within two to four hours of incubation more than half of the mucin was degraded. At pH 5.2 it took twice as long. It is concluded that pouchitis possibly results from instability of the flora in the pouch, which causes homeostasis to disappear (dysbiosis), and the protection of the pouch epithelium by the mucus layer becomes affected by increased activity of bacterial and host derived enzymes. PMID- 8200562 TI - Morbidity of juvenile onset inflammatory bowel disease: effects on education and employment in early adult life. AB - Seventy young adults (50 with Crohn's disease (CD) and 20 with ulcerative colitis (UC) (from a geographically derived cohort of patients with juvenile onset inflammatory bowel disease were interviewed and examined at a mean of 14 (range 5.2-29.5) years after diagnosis. Details of education and employment were collected as part of a structured clinical interview. Although 57% had had periods of absence from school of two months or more, their school examination pass rates were similar to those of the healthy population. The achievements of CD patients were consistently better than those of the UC group. In 15 patients, relapses of inflammatory bowel disease had adversely affected examination performance or prevented them from sitting school examinations. Extra tuition in hospital had been provided for only four patients, and three others had had privately arranged tuition at home. Fifty per cent proceeded to full time higher education. At the time of review, seven patients were full time students, one was a university research fellow, 47 were in full time and three in part time employment, one was self employed, four were housewives, and only six were involuntarily unemployed. All four unemployed CD patients attributed this to inflammatory bowel disease, but other factors were relevant in the unemployed UC patients. Few had direct evidence of rejection by employers on health grounds, though some did not declare their illness to prospective employers. PMID- 8200563 TI - Increased macrophage subset in inflammatory bowel disease: apparent recruitment from peripheral blood monocytes. AB - Mucosal specimens from active Crohn's disease (ileum, n = 6; colon, n = 6), active ulcerative colitis (n = 9), normal ileum (n = 6), and normal colon (n = 6) were subjected to paired immunofluorescence staining for characterisation of macrophage subsets in situ. In the normal state, only few CD68+ macrophages (< 10%) expressing the myelomonocytic L1 antigen (calprotectin) were seen. In inflamed mucosa, especially near small vessels, the CD68+L1+ fraction increased with the degree of inflammation, near ulcers to median 65% (range 35-91%). Cells reactive with the monoclonal antibody RFD7 were also increased in inflammation but less than 5% of them costained for L1 antigen. It is concluded that L1 producing macrophages are distinct from the RFD7+ subset and probably recently recruited from peripheral blood monocytes. Like granulocytes, L1+ macrophages may be important in non-specific defence, providing calprotectin with putative anti microbial and anti-proliferative properties. PMID- 8200564 TI - Patients with adenomatous polyps and carcinomas have increased colonic mucosal prostaglandin E2. AB - Colorectal carcinoma in humans and animal models is associated with increased synthesis of prostaglandin E2 (PGE2). PGE2 synthesis was measured in normal and neoplastic human colorectal mucosa to investigate its role in the adenoma carcinoma sequence. Paired mucosal biopsy specimens for PGE2 synthesis and histological examination were obtained during 39 diagnostic colonoscopies. Twelve control patients in whom colonoscopies and histology were normal synthesised similar amounts of PGE2 at all sites. Their results were (mean (SD) pg PGE2/mg tissue) caecum 102.8 (15.9) (n = 6), ascending colon 110.8 (24.3) (n = 10), transverse colon 103.9 (19.5) (n = 11), descending colon 102.9 (23.2) (n = 12), sigmoid colon 96.4 (18.0) (n = 12), and rectum 107.1 (17.6) (n = 12). Nineteen patients had a total of 27 adenomatous polyps (rectum (1), sigmoid (22), descending (1), transverse (1), and ascending colon (1): histology-tubular (16), tubulo-villous (8), and villous adenomous (3)). The polyps (178.0 (55.0), n = 27) synthesised more PGE2 than controls (p < 0.001), but the values in polyp associated mucosa (mean (SD) 115.4 (21.9), n = 15) were not different to control results. Eight patients had carcinomas (rectal (2), sigmoid (4), and caecal (2)) all of which were adenocarcinomas. The cancers (193.6 (40.2), n = 8) synthesised more PGE2 than control specimens (p < 0.001), but were not different to polyps. Cancer-associated mucosa (140.3 (27.7) n = 8) synthesised more PGE2 than control and polyp-associated mucosa. Colorectal neoplasia is associated with a progressive increase in PGE2 synthesis which may have a role in tumourigenesis and be a pathophysiological explanation for the beneficial effects of NSAIDs in animal models and human disease. PMID- 8200565 TI - Functional hyposplenism in alcoholic liver disease: a toxic effect of alcohol? AB - Functional hyposplenism, seen in some patients with alcoholic liver disease, may contribute to the increased susceptibility to infections. As hyposplenism does not complicate non-alcohol related chronic liver disease, it is probably secondary to a toxic effect of alcohol. Over a two year period the case notes of 82 patients with alcoholic liver disease, whose splenic function had been assessed by the counting of pitted erythrocytes using differential interference microscopy, were reviewed to monitor mortality and the effects of hyposplenism. Thirteen patients (seven with hyposplenism) had serial measurements of pitted erythrocyte count made to assess the effect of abstinence from alcohol on splenic function. Thirty one of the 82 alcoholic patients had pitted erythrocyte counts greater than 2%. Eighteen of 82 (16%) patients died over the two years and 11 of these had been unable to stop drinking. Only one patient died of sepsis. Five patients (6%) had pitted erythrocyte counts comparable with those in splenectomised patients. In 12 of 13 patients who had abstained from alcohol for two months, the pitted erythrocyte count fell from a median of 3 to 1.3% (mean: 8.1 to 2.6%. p = 0.01). The pitted red cell count in two patients increased. One had abstained, the other had continued to drink heavily. Short term mortality in alcoholics is high, particularly if they continue to drink heavily. Only a few of these deaths are secondary to infection. Splenic function, as assessed by these methods, improves in most patients with abstinence, suggesting that the functional hyposplenism may be a result of a direct toxic effect of alcohol on the spleen. PMID- 8200566 TI - Measurement of androgen receptor expression in adult liver, fetal liver, and Hep G2 cells by the polymerase chain reaction. AB - Hepatocellular carcinoma is the most commonly fatal malignant tumour worldwide. The role of androgen receptors, which have been found in hepatocellular carcinoma, is controversial. Sequence specific polymerase chain reaction (PCR) was used to quantify, for the first time, the expression of androgen receptor in four adult liver biopsy specimens (HL-A to HL-D), fetal liver, and Hep-G2 cells. The measurement of androgen receptor is expressed as a ratio (androgen receptor: beta-actin) of the value of androgen receptor to the value of a control gene, beta-actin. The value of the androgen receptor: beta-actin ratios for HL-A, HL-B, HL-C, HL-D, fetal liver, and Hep-G2 were 0.37, 0.86, 0.37, 0.44, 0.87, and 0.66 respectively. To verify sequence specific amplification of the androgen receptor, the PCR androgen receptor fragment was sequenced. The resultant sequence data for both strands of the double stranded PCR androgen receptor fragment had 100% similarity with the published androgen receptor mRNA sequence (complete codons). PMID- 8200567 TI - Combined (short-term plus longterm) sclerotherapy v short-term only sclerotherapy: a randomised prospective trial. AB - Short term sclerotherapy (by injection(s) around the bleeding point) is used for immediate control of massive haemorrhage from oesophagogastric varices. The usefulness of longterm sclerotherapy once short term sclerotherapy has been successfully carried out was assessed. Two treatment groups were studied: 50 patients were treated by 'combined' (short term followed by longterm) sclerotherapy; 56 patients were treated by short term sclerotherapy only. Patients included in the second group were treated by short term sclerotherapy only if a variceal rebleeding was present. The overall cumulative proportion of patients rebleeding was not significantly different in either group. Combined sclerotherapy patients, however, experienced less episodes of variceal haemorrhage and the source of haemorrhage was different (p < 0.002). Combined sclerotherapy was more efficient in preventing bleeding from oesophageal bleeding points but not those arising from a junctional source (p < 0.05). A greater incidence of oesophageal rebleeding was found in those patients whose first source of bleeding was oesophageal (p < 0.05). No significant difference was detected in survival expectancy between either group. In conclusion, after short term sclerotherapy is carried out successfully, those patients with bleeding from variceal bleeding points located on oesophageal mucosa should benefit most from a longterm sclerotherapy programme. PMID- 8200568 TI - Percutaneous cholecystolithotomy: is gall stone recurrence inevitable? AB - Using radiological interventional techniques the gall bladder can be cleared of stones with a high success rate. As with any treatment option that leaves the gall bladder in situ there is an accompanying risk of stone recurrence, which is currently unknown for the radiological method. One hundred patients were studied prospectively to determine the recurrence rate of stones and clinical outcome after successful percutaneous cholecystolithotomy. Follow up included both clinical assessment and ultrasound examination at 3, 6, and 12 months and then annual intervals thereafter. The overall stone recurrence rate was 31% at a mean follow up of 26 months (range, 3-50 months). By actuarial life table analysis, the cumulative proportion of gall stone recurrence was 7, 19, 28, 35, and 44% at 6, 12, 24, 36, and 48 months respectively. Of the 31 patients with recurrent stones; 17 remain asymptomatic, seven have experienced biliary colic, two abdominal pain, three non-specific upper gastrointestinal symptoms, and two jaundice secondary to common duct stones. Thirteen of the stone free patients have remained symptomatic; six with abdominal pain and seven with nonspecific upper gastrointestinal symptoms. Eight patients have subsequently had a cholecystectomy. No significant difference was found between the sex of the patient or the number of stones before treatment and the stone recurrence rates. The cumulative stone recurrence rate was significantly less in the 56 patients who received adjuvant chemolitholysis (p < 0.05). These data show that stone recurrence after successful percutaneous cholecystolithotomy occurs in the minority, and is usually asymptomatic. It is concluded that the technique remains justified in the management of selected patients with gall stones. PMID- 8200569 TI - Genetics of inflammatory bowel disease. PMID- 8200570 TI - Healing of protein losing hypertrophic gastropathy by eradication of Helicobacter pylori--is Helicobacter pylori a pathogenic factor in Menetrier's disease? AB - Hypertrophic gastropathy--that is, Menetrier's disease--was found, in a retrospective analysis, to be associated with Helicobacter pylori in more than 90% of patients. It is proposed that hypertrophic gastropathy represents a special form of H pylori gastritis in these patients. A case is described of a 28 year old woman with Menetrier's disease associated with proved protein loss from the stomach. Treatment with cimetidine for more than three years had little benefit when colonisation by H pylori was detected. Density of H pylori colonisation and activity of gastritis, which was also present in the first biopsy specimens taken five years ago, were more pronounced in the body than in the antrum, which is in agreement with the characteristics of H pylori gastritis found in other cases with Menetrier's disease. A 14 day antibacterial treatment course with 750 mg amoxicillin three times a day combined with 40 mg omeprazole three times a day was started in April 1991. This resulted in eradication of H pylori and the return to normal of giant folds and the mucosal histology. Serum protein concentrations returned to normal within six weeks and remained normal at two endoscopies during a two year follow up. This case report suggests that a subgroup of the patients with Menetrier's disease may be healed by the eradication of H pylori. PMID- 8200571 TI - Biliary obstruction resulting from Strongyloides stercoralis infection. Report of a case. AB - Hepatobiliary manifestations of strongyloidiasis are rare. A case is described of biliary obstruction associated with the presence of Strongyloides stercoralis in the duodenal mucosa and 250 microns rhabditiform larvae in bile. Biliary obstruction resulted from papillary stenosis, which resolved after treatment with thiabendazole. It is proposed that papillary stenosis may be responsible for obstructive jaundice associated with Strongyloides stercoralis infection, and that strongyloidiasis should be added to the causes of papillary stenosis. PMID- 8200572 TI - Diagnostic pitfall; interpretation of CA 19-9 concentrations in the presence of hepatic dysfunction. AB - A 50 year old man is described with hepatic dysfunction and chronic pancreatitis in whom greatly increased concentrations of the pancreatic tumour marker CA 19-9 combined with an abnormal appearance at endoscopic retrograde cholangiopancreatography lead to the false suspicion of pancreatic carcinoma. CA 19-9 concentrations should be interpreted with caution in patients with intrinsic liver disease or biliary obstruction. PMID- 8200573 TI - Spontaneous bacterial peritonitis in cystic fibrosis. AB - Bacterial peritonitis presents with classic symptoms of fever and abdominal pain. Some patients, however, are completely asymptomatic. Death in the short term is considerable, especially in patients with alcoholic cirrhosis. Cystic fibrosis patients occasionally develop biliary cirrhosis and may have secondary hypersplenism, varices, and ascites. These patients should be at risk for spontaneous bacterial peritonitis. Spontaneous bacterial peritonitis is described in two patients with longstanding hepatic cirrhosis secondary to cystic fibrosis. Both had required splenectomy for complications of portal hypertension. This is a previously unreported, but potentially fatal, complication of cystic fibrosis liver disease. Early diagnostic paracentesis is essential so that appropriate acute management, including antimicrobial treatment can be started. In the long term, these patients deserve immediate paracentesis for any evidence of recurrence. Whether the patient is treated with chronic (continuous) antimicrobial prophylaxis or only receives antimicrobial treatment during periods when bacteraemia is possible (for example, dental work, bronchoscopy), it would seem reasonable in patients with cystic fibrosis to use a wide spectrum antimicrobial agent with activity against Pseudomonas aeruginosa, other common Gram negative organisms, and Staphylococcus aureus. PMID- 8200574 TI - Pancreatitis induced by nitrofurantoin. AB - The case of a woman is described who suffered from acute pancreatitis related to the ingestion of low dose nitrofurantoin, as shown by involuntary rechallenge. Because this is only the second case reported in published works, this side effect must be rare and is probably dependent on individual susceptibility. PMID- 8200575 TI - Cytokine production in inflammatory bowel disease. PMID- 8200576 TI - Oesophageal acid clearance. PMID- 8200577 TI - Tumor necrosis factor alpha in inflammatory bowel disease. PMID- 8200578 TI - Mycobacteria in the human intestine. PMID- 8200579 TI - Helicobacter pylori infection. PMID- 8200580 TI - Aldehyde disinfectants and health in endoscopy units. PMID- 8200581 TI - [Intracavernous auto-injection of prostaglandin E1 for diagnosis and treatment of erectile dysfunction]. AB - 34 impotent patients were offered auto-injection therapy and all except 2 began treatment. Prostaglandin E1 (PGE) was used regularly for a mean of 8.6 months (range 1-17). The onset of erection was 5-30 min (mean 11.4) after injection and it lasted at least 30 min (mean 106.2 min). An erection of more than 6 hrs was observed in only 2 patients. There have been no instances of cavernous fibrosis, chemical priapism or systemic reactions. The most common adverse effect was penile pain after injection. It was mild to moderate in 4 patients (11.7%), and in only 1 was it severe enough to require stopping treatment. Overall, intracavernous injection of PGE appears to be safe, effective treatment for impotence without side-effects other than pain after injection in a few. PMID- 8200582 TI - [Decreased interleukin-1 and interleukin-2 production after splenectomy]. AB - Production of interleukin-1 and of interleukin-2 was measured in 57 splenectomized patients. 11 of them were after elective operations (aged 14-37 years, mean 24) and 46 posttraumatic (aged 20-36, mean 23) and in 20 appropriate controls. There was significant reduction of both interleukins in the splenectomized group, more evident in the elective group. The deficiency was not related to age of patient or time since splenectomy. These results support the view that a consequence of splenectomy is immunoregulatory deficit. PMID- 8200583 TI - [Microalbuminuria and ischemic heart disease in noninsulin-dependent diabetes]. AB - Prospective studies showed that hypersecretion of albumin in the urine of patients with type 2 diabetes mellitus is associated with high morbidity and mortality from cardiovascular disease and nephropathy. 65 type 2 diabetes from 6 family medicine practices were studied. Microalbuminuria was found in 37% and was significantly more common in men than in women (53% and 23%, respectively; p < 0.02). Uncontrolled blood glucose levels were also more common in men (p < 0.03). Using logistic regression with microalbuminuria as the dependent variable, a significant correlation was found with male gender, fasting blood glucose 155 mg/dl or more, and systolic blood pressure 159 mm Hg or higher. Among those with microalbuminuria, ischemic heart disease was significantly more common in those 65 years or older than in those younger (p = 0.02). This study strengthens the assumption that type 2 diabetics with microalbuminuria might be at greater risk for developing ischemic heart disease. Strict detection and control are recommended. PMID- 8200584 TI - [Herpes zoster treated with acyclovir]. AB - During the past 5 years, 99 patients with herpes zoster were hospitalized and followed. Age, sex, localization of rash, complications, duration of hospitalization and treatment were analyzed. Most patients were in their 6th and 7th decades. Cranial nerve involvement was frequent (35%). A generalized rash was more common in those with immunodeficiency. Acyclovir (Zovirax) inhibited to some extent the spreading of the rash and reduced the frequency of herpetic neuralgia. Our findings are in accord with those in the literature. PMID- 8200585 TI - [Lateral sinus thrombophlebitis]. AB - Lateral sinus thrombophlebitis (LST) is an intracranial complication of otitis media. Its incidence has markedly decreased in the era of antibiotic therapy but mortality is still high. A 13-year-old girl presented with fever, ear discharge and torticollis. On the day of admission LST was diagnosed from the clinical presentation and CT-scan. She was operated immediately and intravenous antibiotics were administered. Despite the rapid intervention, the course was protracted, with recurrent events of septic pulmonary embolism. Despite internal jugular vein ligation, fever continued and anticoagulant therapy was begun. The possibility of LST should be considered in patients with ear discharge and fever. CT-scan enables early diagnosis of LST and MRI has a role in detecting additional intracranial septal foci. Surgical intervention should be early and aggressive. The efficacy of jugular vein ligation is unclear; anticoagulant therapy should be considered. PMID- 8200586 TI - [Metabolic status of the fetus during labor]. PMID- 8200587 TI - [Portal hypertension--a multisystem disease]. PMID- 8200588 TI - [Inhaled corticosteroids--a safe treatment for asthma?]. PMID- 8200589 TI - [The relationship between problems of fertility and pregnancy and the development of rheumatoid arthritis]. PMID- 8200590 TI - [Achilles tendinitis]. PMID- 8200591 TI - [Health concerns of Israelis traveling to Third World countries--experience of a travel advisory clinic]. AB - Following army service young Israelis often travel to remote third world regions for prolonged periods. During such tours, they are exposed to a variety of medical problems, including infections, environmental diseases, political violence and inability to obtain proper medical care. From May 1991 to Nov. 1992, 1,969 travelers aged 20-25 years old, and 926 older than 25, were given medical advice, vaccines and medications prior to travel. A clinic specializing in "emporiatrics" has been established to deal with pre- and post-travel medical problems associated with tourism. PMID- 8200592 TI - [Passover hand injuries]. AB - Almost every year just before Passover there is increased exposure to hand trauma in matzah bakeries. In the past 5 years we treated 11 cases of hand trauma incurred during matzah baking. The typical injuries were amputations at different levels, crush injuries and burns. We present a case seen last Passover and suggest preventive methods to eliminate these accidents in the future. PMID- 8200593 TI - [Autopsy and halacha]. PMID- 8200595 TI - [How many author names on one medical article?]. PMID- 8200594 TI - [Effects of exercise on renal water and electrolyte status: acid-base regulation]. PMID- 8200596 TI - [Management of diabetes in general practice--current requirements. 1: Diagnosis, pathophysiology and overall therapeutic concept]. AB - Plasma glucose determinations continue to be at the heart of the proper diagnosis and monitoring of diabetes mellitus, the post-prandial values in particular being of decisive importance for the diagnosis. Laboratory diagnostic investigations going beyond this (e.g. the oral glucose tolerance test) are reserved for special indications. In contrast, the determination of microalbuminuria is of increasing importance for deciding on the next therapeutic steps. Prerequisites for successful treatment are patient instruction, treatment of the metabolic disorder including diet and physical exercise, and self-monitoring by the patient. Of fundamental importance for treatment is the diet, with calorie reduction in type 2 diabetics, most of whom are obese. PMID- 8200597 TI - [Screening studies in diagnosis of diabetes. Do they still have practical value?]. AB - The WHO has defined standardized diagnostic criteria for manifest diabetes mellitus and disorders of glucose tolerance. Owing to a low level of sensitivity and only moderate specificity, coupled with an unfavorable cost-benefit rating, glucosuria screening is not suitable for large-scale use at population level and, as recommended by the WHO, should be replaced by plasma glucose screening. The method of choice for the latter is the determination of the fasting plasma glucose level. Its use should be restricted to target groups with a high risk of contracting diabetes. In the doctor's office, a health check is of particular importance for the diagnosis of type 2 diabetes, which is usually asymptomatic. Screening for diabetes with the aid of a 50 g oral dose of glucose to detect gestational diabetes is a must during pregnancy. PMID- 8200598 TI - [Liaison psychiatry in an internal medicine clinic. Study of a subgroup of patients with psychogenic reactions and neurotic disorders]. AB - Too little attention is paid to psychiatric consultation activities--and this also applies to the literature. Within the framework of an overall consideration of patients passing through a psychiatric consultation service in 1989 and 1990 at the Medical Department of the University Hospital in Ulm, the largest subgroup of patients with psychogenic reactions and neuroses were examined in detail. Among the psychiatric disorders diagnosed, anxiety disturbances clearly predominated. Among the psychogenic reactions these latter presented in the form of body-related anxiety and among the neurotic patients more often as a diffuse feeling of anxiety. With respect to the acceptance of the diagnoses and the passing-on of the therapeutic recommendations by the internist, certain reservations were observed, in particular involving patients with psychogenic reactions, which in the first instance were induced by the disease and associated diagnostic and therapeutic measures. For this patient group, however, more intensive management with respect to further treatment could be very helpful. PMID- 8200599 TI - [Current developments in antiviral chemotherapy. 2: Acyclovir]. PMID- 8200600 TI - [Bronchial asthma: use of combination therapy. Anti-obstructive and anti inflammatory treatment--result of treatment]. AB - On the basis of a single case report, combined antiobstructive and anti inflammatory treatment of bronchial asthma is described. The anti-obstructive component used was a sustained-release theophylline preparation (Euphylong, 750 mg/day), and as anti-inflammatory drug, the inhalant beclomethasone diproprionate (Viarox, 300 mg/day). During the 4-week treatment period, obvious improvements in lung function parameters (FEV1 from 21 prior to to 31 after treatment; FVC from 2.81 to 3.31) were seen. At a daily dose of 750 mg theophylline, a favorable therapeutic concentration of 16.5 micrograms/ml was achieved. It was found that the combination of sustained-release theophylline and the low-dose glucocorticoid inhalant resulted in an impressive improvement in bronchial asthma. PMID- 8200601 TI - [Biotechnology vaccines--development of new disease prevention. Research progress of Biocine in Siena--HIV, herpes, Helicobacter]. PMID- 8200602 TI - [Management of diabetes in general practice--current requirements. 2: Oral antidiabetics and insulin therapy]. AB - Oral antidiabetic agents continue to play an important role in the treatment of type 2 diabetes. Of decisive importance is the timing of their use, together with a knowledge of their specific properties. Acarbose, which needs to be initiated at a low, slowly increasing dose, is noted for the fact that it has virtually no systemic side effects. Metformin reduces plasma glucose levels without inducing hyperinsulinemia, and carries virtually no risk of lactic acidosis. Glibenclamide can be used either alone to treat type 2 diabetes or in combination with other oral antidiabetics or insulin. Today, intensified insulin therapy represents the optimal standard of insulin replacement. It permits meal-oriented injection of normal insulin and the use of longer-acting insulin overnight. This form of treatment is now facilitated by the possibilities of plasma glucose selfmonitoring and the use of injection aids (pen). Intensified treatment should be initiated at the time type I diabetes is diagnosed. In the case of a particularly instable metabolic situation or neuropathy, it may become necessary to use insulin pumps. PMID- 8200603 TI - [Leukemia in advanced age. 1: Acute leukemia]. AB - Acute leukemia is a disease of the elderly. In this group of patients, possible effects of chemotherapy must be taken into account and, as far as possible, the patient's general state of health stabilised prior to treatment. The complexity of the treatment is further increased by supportive measures, which should be applied both rigorously and with care. The therapeutic concept must take account of the quality of life of the elderly patient. PMID- 8200604 TI - [Current developments in antiviral chemotherapy. 3: Vidarabine, ganciclovir]. PMID- 8200605 TI - [Is dopaminergic therapy immunologically rejuvinating? Increased interferon-gamma production with the dopaminergic agent lisuride]. AB - Eighteen patients with advanced Parkinson's disease (n = 13) or dopamine sensitive dystonia (n = 5) were treated with the dopaminergic agent, lisuride, applied as a long-term subcutaneous infusion. The results were compared with those obtained in a group of younger, and a group of older, healthy volunteers. The liberation of gamma-interferon (gamma-IFN) following mitogenic stimulation of whole blood with phytohemagglutinin (PHA) was highly significantly elevated in comparison with the group of older healthy volunteers, and clearly, but not significantly, elevated in comparison with the younger group. There was no difference between patients with dystonia and those with Parkinson's disease. The effect observed is thus probably due to lisuride. This effect might explain the longer life expectancy and reduced proclivity for infection shown by patients with Parkinson's disease. It needs to be determined whether, on the basis of these initial data, a therapeutic principle for the treatment of diseases that can be directly influenced by gamma-IFN can be derived. PMID- 8200606 TI - [AIDS: management still inadequate. Ambulatory care--AIDS counseling]. PMID- 8200607 TI - [Recent topics on immunologic disorders and physiopathology of systemic lupus erythematosus]. PMID- 8200608 TI - [The effects of female hormone on the temporary threshold shift (TTS) of men]. AB - The purpose of the present study was to investigate the effects of female hormone on the temporary threshold shift (TTS) of men. Female hormone (estrogen or progesterone or progesterone with estrogen) were administrated to eight male subjects. TTS was measured under the administration of female hormone and control (no administration of female hormone). The subjects were exposed to continuous white noise of 100 dB for 8 min after 5 min rest. The audiometry was performed in 1,000, 2,000, 3,000, 4,000, 6,000 and 8,000 Hz test tones at 2, 5, 10, 15, 20, 25 and 30 min of recovery process. TTS at 3,000 and 4,000 Hz was smaller under the condition of progesterone with estrogen administration than under the other conditions. TTS under the condition of estrogen administrated was smaller at 4,000 Hz than under the condition of progesterone administrated or under the control condition, but greater at 6,000 Hz than under the other conditions. These results indicate that TTS at 3,000 and 4,000 Hz is affected by progesterone with estrogen, and TTS at 6,000 Hz by estrogen. PMID- 8200609 TI - Experimental autoimmune myasthenia gravis induced by thymic acetylcholine receptor-like protein. AB - The trigger mechanism of autoimmunity in myasthenia gravis (MG) has yet to be elucidated. To determine the function of the thymus in the pathogenesis of MG, we tried to produce chronic experimental autoimmune myasthenia gravis (EAMG) using nicotinic acetylcholine receptor-like protein (n-AChR-LP) isolated from the fetal calf thymus (FCT) by affinity chromatography with Sepharose-4B bound cobrotoxin. Lewis rats were inoculated with n-AChR-LP emulsified in Freund's complete adjuvant and later received two booster immunizations. The immunized rats developed generalized hypotonia at seven to ten days and then recovered spontaneously within two weeks. In the fourth week, flaccid paresis with either a hunched posture or waddling gait appeared in half of the rats, these symptoms improved transiently after treatment with neostigmine. At this time, evoked EMG showed decremental responses after curare sensitization, while anti-n-AChR-LP antibody, measured by enzyme-linked immunosorbent assay (ELISA), increased significantly. These findings therefore suggest that the n-AChR-LP from the thymus includes antigens to induce EAMG. PMID- 8200610 TI - Symptomatic bilateral extracranial internal carotid artery aneurysms- successfully treated by unilateral aneurysmectomy and saphenous vein graft. AB - A Japanese case of bilateral extracranial internal carotid artery aneurysms is presented. The main symptom was transient cerebral ischemic attack (TIA) of the right side. An aneurysmectomy and autogenous saphenous venous interposition of the left internal carotid artery were performed. After the operation, the patient has not suffered from TIA. PMID- 8200611 TI - Tamoxifen and norethisterone: effects on plasma cholesterol and total body calcium content in the estrogen-deficient rat. AB - It is important that drugs which are used to protect bone from the osteoporotic effects of estrogen deficiency should not affect plasma lipids adversely. Effects of a) norethisterone acetate and b) tamoxifen citrate on plasma cholesterol and on bone conservation in rats with normal plasma 17B-estradiol and in rats made estrogen-deficient with the LHRH agonist, buserelin are reported. Tamoxifen halved total plasma cholesterol (p < 0.01), whereas norethisterone did not lower plasma cholesterol. Furthermore tamoxifen fully protected bone from estrogen deficiency osteopenia whereas norethisterone conserved bone less well. Reductions in cholesterol elicited by tamoxifen were similar in estrogen-deficient rats and in rats with normal ovarian function. This is the first report in the rat that tamoxifen has lipid-lowering actions. It is suggested the rat may be useful for future investigations of the lipid-lowering mechanisms of tamoxifen. PMID- 8200612 TI - The relationship between hyperthyroidism and the distribution of peripheral blood T, NK and B-lymphocytes in multinodular goiter. AB - Peripheral blood T, NK and B-cell subsets were analyzed in 18 patients with nontoxic multinodular goiter (NMG) and 11 patients with toxic multinodular goiter (TMG) in order to evaluate whether hyperthyroidism modifies the distribution of these cell populations. As a control group, 26 age and sex-matched healthy individuals were included in the study. Lymphoid subsets were analyzed with flow cytometry by double staining immunofluorescence techniques using a large panel of monoclonal antibodies. No differences were found in the absolute or relative numbers in any of the cell populations analyzed in both groups--NMG and TMG--, with the exception of a significant decrease in CD19+ cells in TMG. However, patients with multinodular goiter showed important abnormalities in the distribution of T, NK and B lymphocytes with respect to the control subjects. The pattern of abnormalities detected was characterized by a marked increase in the absolute and relative counts of activated T-lymphocytes (CD3+/HLA-DR+), cytotoxic T-cells (CD57+/CD8+) and of cells expressing NK-related antigens. None of these alterations were related to the serum levels of T3, T4 or TSH. Our results point to the existence of important abnormalities in the distribution of several lymphoid subsets in multinodular goiter, regardless of whether the subjects are euthyroid or hyperthyroid. PMID- 8200613 TI - Insulin effect on interleukin 1 (IL-1) and interleukin 6 (IL-6) production by lipopolysaccharide-stimulated human monocytes. PMID- 8200614 TI - Pertussis toxin enhances fetal calf serum-induced alkaline phosphatase activity in osteoblast-like cells. PMID- 8200615 TI - Increased plasma endothelin levels in patients with insulin-dependent diabetes mellitus and end-stage vascular complications. PMID- 8200616 TI - On the relation of atrial natriuretic peptide and cyclic guanosine 3',5' monophosphate plasma concentrations during ergometric exercise in healthy individuals. PMID- 8200617 TI - Assessment of bioactivity of WHO/NIH research standard for inhibin [code 86/690] using two separate pituitary cell culture systems. PMID- 8200618 TI - The IGF axis in the prostate. AB - The insulin-like growth factor (IGF) axis is a multi-component network of molecules involved in the regulation of cell growth. The axis includes two major ligands, (IGF-I and IGF-II), cell surface receptors, (the type I IGF receptor family as well as the type II IGF receptor), a family of high affinity binding proteins which regulate IGF availability to the receptors, (the IGFBPs), and a group of IGFBP proteases which cleave IGFBBPs and modulate IGF action. Human seminal plasma contains IGF-I and -II, IGFBP-2 and -4, as well as IGFBP-3 fragments and IGFBP-3 protease activity. A prostatic source for these IGF-axis molecules is likely. We have demonstrated the human prostate to contain all the elements of a functional IGF system. Prostate fibroblasts in primary culture (PC F) express mRNA for IGF-II and produce IGF-II peptide in biologically active concentrations. This IGF-II appears to be of a high molecular weight (15 kD) species. Prostate epithelial cells in primary culture (PC-E) express the type I IGF receptor. These cells also produce IGFBP-2 and -4, (on both mRNA and peptide levels), while PC-F secrete IGFBP-2, -3 and -4. PC-E are exquisitely sensitive to the mitogenic effects of IGFs. Finally, prostate specific antigen (PSA), secreted from PC- and found in seminal plasma, can function as a potent IGFBP-3 protease. This IGFBP-3 protease activity can remove the inhibitory effects of IGFBP-3 on IGF-I induced PC-3 growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200619 TI - Fatty acid synthesis in obese insulin resistant diabetic mice. AB - Diabetes is associated with hypertriglyceridemia and it has been suggested that the intestine contributes to this elevation. Recent studies have shown that in animals with IDDM, fatty acid (FA) synthesis is decreased in the liver and increased in the small intestine (SI). The purpose of the present study was to measure FA synthesis in the liver and SI of animals with NIDDM. In both db/db and ob/ob animals the incorporation of 3H2O into FA was increased in the SI (10 fold in db/db and 2.2 fold in ob/ob). FA synthesis was also increased in the liver of NIDDM (9 fold in db/db and 6 fold in ob/ob). These results provide further evidence that diabetes leads to changes in lipid metabolism in the SI. PMID- 8200620 TI - Regulation of glucose utilization during the inhibition of fatty acid oxidation in rat myocytes. AB - The study of the regulation of glucose utilization by inhibition of fatty acid oxidation is greatly enhanced by the availability of specific inhibitors of fatty acid oxidation. This study examines the regulation of cardiac glucose utilization by inhibition of fatty acid oxidation at different sites. The effects of Etomoxir and 4-bromocrotonic acid (4-BCA) on the oxidation of [1-14C]palmitate, [1-14C] octanoate and [U-14C]glucose were studied in isolated rat myocytes. Fifty percent inhibition of palmitate oxidation was achieved at 8 microM Etomoxir and 40 microM 4-BCA. Octanoate oxidation was inhibited only by 4-BCA. In contrast to their effect on palmitate oxidation, these inhibitors significantly stimulated the oxidation of glucose in a concentration-dependent manner. Moreover, the oxidation of [2-14C]pyruvate was increased two-fold by these compounds. The rate of utilization of [U-14C]-2-deoxyglucose was also stimulated 2-3 times by these inhibitors. These studies suggest that the stimulation of glucose utilization via the inhibition of fatty acid oxidation may be mediated through the stimulation of both glucose transport and the oxidation of pyruvate by the pyruvate dehydrogenase complex. PMID- 8200621 TI - Immunohistochemical detection of p53 in differentiated, poorly differentiated and undifferentiated carcinomas of the thyroid. AB - In an attempt to find whether or not p53 immunoreactivity in the thyroid gland is restricted to undifferentiated carcinomas and to evaluate the putative prognostic usefulness of its detection, we investigated p53 immunoreactivity in a series of 14 benign thyroid lesions and 65 thyroid carcinomas (12 papillary; six minimally invasive follicular; four widely invasive follicular; 31 poorly differentiated and 12 undifferentiated tumours). Unequivocal nuclear immunostaining for p53 was observed in two widely invasive follicular carcinoma (20.0%), five poorly differentiated carcinomas (16.1%) and in 10 undifferentiated carcinomas (83.3%). The percentage of immunoreactive cells was much smaller in the former groups than in undifferentiated carcinomas. Despite a trend to a more aggressive behaviour of the p53 immunoreactive cases no significant differences in the outcome of patients with positive and negative tumours was found when the comparison was made within each category of carcinomas. We conclude that p53 immunoreactivity can be detected both in undifferentiated carcinomas and in some differentiated and poorly differentiated thyroid carcinomas. Larger series of cases are necessary to evaluate the prognostic usefulness of this finding. PMID- 8200622 TI - p53 immunostaining suggests that uterine carcinosarcomas are monoclonal. AB - The histogenesis of carcinosarcomas has intrigued pathologists for a long time and remains unresolved. Two main theories have been put forward, one suggesting that they are monoclonal, another suggesting that they are biclonal. Our study examined p53 immunostaining in 17 uterine carcinosarcomas (mixed Mullerian tumours) and found positivity in five (30%). There was no disparity in immunostaining between the epithelial and the stromal components in any of the 17 tumours. This concordance in every tumour would be very unlikely if carcinosarcomas are biclonal. However, it would be expected if carcinosarcomas are monoclonal. PMID- 8200623 TI - Lymphatic amyloidosis, a previously unrecognized form of amyloid deposition in generalized amyloidosis. AB - Although amyloid deposition in relation to blood vessels is a well-recognized feature of generalized amyloidosis, lymphatic vessel amyloidosis is not mentioned in the literature. Systematic investigation of tissue removed at autopsy from patients with generalized amyloidosis and biopsy specimens from cases of localized amyloidosis and familial Mediterranean fever showed that amyloid deposition around lymphatics is by no means uncommon. The material investigated was mainly large and small bowel, lung, heart and kidney. Amyloid was identified by green birefringence with the Congo red stain on cross-polarization and lymphatics by their lack of immunostaining for CD34. Involvement of lymphatics was noted in 20 of the 42 organs from which specimens were examined, and was always accompanied by involvement of blood vessels and/or the interstitium. In the intestine, lymphatic amyloidosis was found mainly in the submucosa and subserosa, and was also demonstrated by electronmicroscopy in one case. Although lymphatic amyloidosis was equally common in the heart, lung and kidney, it was usually less prominent here than in the intestine. No lymphatic involvement was seen in localized amyloidosis. As the lymphatics play a central role in the resorption of interstitial proteins, they are probably also involved in the resorption of amyloid proteins. Amyloid deposition in the vicinity of lymphatics is probably the result of decompensation of this process. PMID- 8200624 TI - Granular cell change in smooth muscle tumours of skin and soft tissue. AB - Nine smooth muscle tumours, arising at a variety of sites and showing granular cell change of their cytoplasm, have been studied morphologically and immunohistochemically. The age of the patients ranged from 6 to 78 years (median 42 years); seven patients were female. Two tumours each arose in the dermis or subcutaneous tissue while the other five cases were situated in deeper soft tissue. Three of the lesions arose in the lower limbs, two in the pelvis and one each in the regions of the elbow, shoulder, breast and buttock. Follow-up in eight patients was available and revealed local recurrence in three and pulmonary metastases in two cases. All cases showed at least focally the light microscopic features of a smooth muscle tumour and demonstrated moderate to strong positivity for alpha-smooth muscle actin. Five were also HHF-35 positive and three were desmin positive. Noteworthy was strong positivity for the 'melanoma associated' antigen NKI/C3 in all cases. Six cases stained also weakly positive for NSE, but all were S-100 protein negative. The former is not specific but is the most reliable marker of lesions showing granular cell change. Granular cytoplasmic change represents simply a cytological phenotype, apparently representing a characteristic metabolic alteration, not exclusively associated with Schwann cell tumours. Tumours containing granular cells are best classified according to their line of specific cellular differentiation if possible. PMID- 8200626 TI - Autopsy findings in two cases of neonatal herpes simplex virus infection: detection of virus by immunohistochemistry, in situ hybridization and the polymerase chain reaction. AB - We describe the pathological findings in two fatal cases of neonatal infection with herpes simplex virus. One had an encephalitis caused by herpes simplex virus type 2 (HSV-2); the other had a disseminated infection with herpes simplex virus type 1 (HSV-1). Confirmation of the diagnosis was obtained by use of the polymerase chain reaction to amplify viral DNA from paraffin sections of autopsy tissues. By using primers which amplify fragments of the HSV-1 thymidine kinase gene and HSV-2 glycoprotein gene respectively it was possible to discriminate between infection with HSV-1 and HSV-2. In contrast, immunohistochemistry and in situ hybridization using commercially available reagents did not distinguish between HSV-1 and HSV-2 infection. However, immunohistochemistry and in situ hybridization are probably more reliable than the polymerase chain reaction for assessment of the distribution of virus in different tissues. PMID- 8200625 TI - Extramedullary haemopoiesis in fetal and adult human spleen: a quantitative immunohistological study. AB - Haemopoietic cells were assessed in spleens from normal adults, adults with splenic extramedullary haemopoiesis due to chronic myeloproliferative disorders and fetuses of 17-21 weeks' gestation. A variety of antigens expressed by developing granulocytes and erythrocytes were demonstrated immunohistochemically. The relative proportions of early and late precursor cells of these two lineages were quantified. There was no significant haemopoiesis in normal adult spleen, while there was abundant (predominantly granulocytic) haemopoiesis in patients with chronic myeloproliferative disorders. Fetal spleens contained numerous late erythroid precursors but few early erythroid or granulocytic cells. The relative numbers of early and late haemopoietic cells in adult chronic myeloproliferative disorders and fetal spleens showed statistically significant differences. Our findings indicate that haemopoiesis in the spleens of adult patients with these disorders differs fundamentally from that occurring in fetal life. They support the view that the human spleen does not have a significant role in fetal haemopoiesis, but that it filters circulating nucleated erythroid precursors and is permissive of their terminal differentiation only. Our results also favour the view that adult splenic haemopoiesis originates by displacement of precursor cells from the bone marrow rather than by activation of stem cells which have lain dormant in the spleen since fetal life. PMID- 8200627 TI - Intravascular histiocytosis. AB - The majority of cases of intravascular lymphomatosis are B-cell lymphomas with only the occasional case being of T-cell type. We report a case of intravascular lymphomatosis in which the proliferating cells were of histiocytic type; the tumour has recurred following treatment. PMID- 8200628 TI - Sarcoma-like ovarian nodules associated with retractile mesenteritis and retroperitoneal fibrosis. PMID- 8200629 TI - Angiomyolipoma of the liver with pleomorphic histological features. PMID- 8200630 TI - Osteosarcomatous differentiation in carcinoma of the breast: a case of 'metaplastic' carcinoma with osteoclasts and osteoclast-like giant cells. PMID- 8200631 TI - How may clonality be assessed in human tumours? PMID- 8200632 TI - Radial scars and complex sclerosing lesions. PMID- 8200633 TI - Radial scars and complex sclerosing lesions. PMID- 8200634 TI - Radial scars and complex sclerosing lesions. PMID- 8200635 TI - p53 immunohistochemistry: a word of caution. PMID- 8200636 TI - Overexpression of the oncoprotein p53 in primary hepatic tumors of childhood does not correlate with gene mutations. AB - High levels of expression of the p53 protein and gene mutations have been described in adult hepatocellular carcinomas. It has been postulated that specific mutations in exon 7 may be caused by aflatoxin exposure. To determine whether p53 mutations occur in childhood liver cancer unassociated with aflatoxin exposure or hepatitis B virus (HBV) infection, we have analyzed three histologically distinct tumor types. Two techniques were used to access p53 in the tumors: (1) expression studies of the p53 protein were performed using the polyclonal antibody CM1 and immunohistochemistry, and (2) DNA sequencing was performed. p53 Protein was detectable by immunohistochemistry in 10 of 15 hepatoblastomas, six of nine hepatocellular carcinomas, and one of one embryonal sarcomas. Solid phase single-stranded DNA sequencing across exons 5 through 9 showed normal sequence in all cases. These results indicate that p53 is overexpressed in a majority of childhood liver cancers, but this abnormal p53 expression does not seem to be caused by mutations in the p53 gene. PMID- 8200637 TI - p53 immunostaining in the differentiation of reactive processes from malignancy in pleural biopsy specimens. AB - To determine the utility of positive p53 protein immunostaining as an adjunct in the diagnosis of malignancy in pleural biopsy specimens, we reviewed 73 recently obtained pleural biopsy specimens that represented the typical range of diagnoses encountered in the evaluation of a proliferative pleural process. Immunohistochemistry was performed on paraffin sections of each biopsy specimen using a monoclonal antibody to the p53 suppressor gene product clone BP53-12 (BioGenex, San Ramon, CA) and a standard capillary gap (Microprobe, Fischer Scientific, Pittsburgh, PA) avidin-biotin complex technique with a citrate buffer antigen retrieval solution. Of the pleural biopsy specimens with unequivocal malignancy, 19 of 40 mesotheliomas and nine of 18 metastatic adenocarcinomas were immunopositive for p53 protein. All 13 of the biopsy specimens with reactive mesothelial hyperplasia or organizing pleuritis were negative. Two pleural biopsy specimens, which were interpreted as suspicious but inconclusive for malignancy, were positive for p53 protein and subsequent pathology specimens confirmed the presence of metastatic carcinoma in both of these biopsy specimens. Our findings suggest that p53 protein immunostaining is relatively sensitive and highly specific in differentiating reactive processes from primary or metastatic malignancies in histopathologically equivocal pleural biopsy specimens. PMID- 8200638 TI - Expression of the p53 gene in Hodgkin's disease: dissociation between immunohistochemistry and clinicopathological data. AB - Expression of the p53 protein has been detected recently by immunohistochemistry in Hodgkin's disease (HD), but the relationship between p53 expression and the prognosis and clinicopathological heterogeneity of HD is still unclear. To address these questions we investigated 49 cases of HD for p53 expression by immunohistochemistry using the DO1 monoclonal antibody (MAb) on paraffin sections. Thirty-five cases were simultaneously tested with the 1801 MAb on frozen sections. Thirty-seven of 49 cases (75%) were DO1 positive while 14 of 35 (40%) were PAb 1801 positive. Both MAbs gave a nuclear staining restricted to Reed Sternberg cells (RSCs) and variants and distributed among the three HD subtypes analyzed (ie, nodular lymphocyte predominant, nodular sclerosing, and mixed cellularity). The percentage of positive neoplastic cells in each case was heterogeneous, ranging from almost 100% to less than 5%. In 39 patients for whom clinical data were available statistical analysis did not show any significant correlation between p53-positive immunostaining and clinical staging, B symptoms, probability of relapse, or disease-free survival. We conclude that p53 expression is a common event in HD regardless of histological subtyping, but does not bear any pejorative significance. PMID- 8200639 TI - Monocyte chemoattractant protein-1 in idiopathic pulmonary fibrosis and other interstitial lung diseases. AB - Macrophages play a crucial role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). To examine the mechanisms for increased monocyte/macrophage recruitment in IPF and nonIPF interstitial lung diseases (nonIPF) the localization of monocyte chemoattractant protein-1 (MCP-1) was investigated in 14 cases of IPF, seven cases of nonIPF, and seven normal control lungs (CTRL) by immunohistochemistry using a specific anti-MCP-1 monoclonal antibody, F9. By double immunohistochemical staining using F9 and one of the cell type specific antibodies significant differences in the staining pattern of MCP-1 were observed between IPF and nonIPF. In IPF MCP-1 was observed in cuboidal and flattened metaplastic epithelial cells, alveolar macrophages, and vascular endothelial cells. In contrast, no epithelial cells were stained for MCP-1 in nonIPF cases, although alveolar macrophages and vascular endothelial cells were labeled. Northern hybridization analysis of selected cases showed marked expression of MCP 1 messenger RNA (mRNA) in IPF and nonIPF compared with CTRL. These findings suggest that the MCP-1 production in IPF and nonIPF plays an important role in the recruitment of monocyte/macrophages. Monocyte chemoattractant protein-1 production by epithelial cells in IPF may be caused by the metaplastic nature of the epithelial cells and may be one of the key factors inducing the irreversible progression of IPF. PMID- 8200640 TI - TGF beta 1 and TGF beta 2 are potential growth regulators for medulloblastomas, primitive neuroectodermal tumors, and ependymomas: evidence in support of an autocrine hypothesis. AB - Our previous investigations of transforming growth factor types beta 1 and beta 2 (TGF beta s) showed negative or positive autocrine growth regulation of gliomas in vitro. Near-diploid gliomas were inhibited by the TGF beta s, whereas a stimulatory response correlated with progressive anaplasia and karyotypic divergence. We have tested the hypothesis that cytogenetic aberrations may be associated with conversion of TGF beta autoregulation from inhibitory to stimulatory among other cultured neuroectodermal tumors. Anchorage-independent growth and karyotypic aberrations supported the malignant nature in vitro of two medulloblastoma (MBL), two primitive neuroectodermal tumor (PNET), and two ependymoma (EPD) cultures. Transforming growth factor type beta 1 and/or TGF beta 2 RNA was evident by Northern blot analysis among these cell cultures. By radioreceptor assay active TGF beta was present in conditioned medium in concentrations of 0 to 14 ng/mL, whereas the total amount of active and latent TGF beta secreted was in the range of 3 to 118 ng/mL. Expression of the TGF beta radioreceptor (TGF beta-R) types I and II was shown by cross-linking assay. Responses to exogenous TGF beta were determined by [3H]-thymidine incorporation, cell counts, and anchorage-independent clonogenicity. Exogenous TGF beta was growth inhibitory for the near-diploid MBL, PNET, and EPD in vitro, as well as antagonistic to the mitogenic effect of epidermal growth factor (EGF) and insulin. In contrast, MBL, PNET, and EPD with a hyperdiploid subpopulation were stimulated to proliferate in monolayer culture or soft agar by TGF beta 1 and TGF beta 2. The growth response did not correlate with TGF beta-R type. Autocrine regulation was supported by antibody neutralization experiments performed with quiescent cells in the absence of exogenous TGF beta. Anti-TGF beta antisera enhanced the growth of TGF beta-inhibited cultures, whereas the TGF beta stimulated cultures were inhibited by the antisera. Karyotypic divergence seemed to predict response as MBL, PNET, and EPD with hyperdiploid elements exhibited autocrine TGF beta-stimulation. In contrast, the near-diploid cultures were inhibited by the TGF beta s. By analogy with the gliomas, conversion of TGF beta autocrine regulation from inhibition to stimulation may be a late progression marker of anaplasia among MBL, PNET, and EPD. Secretion of this TGF, which serves both as a mitogen and immunosuppressive agent may contribute to the adverse prognosis of hyperdiploid neuroectodermal neoplasms of the central nervous system (CNS). PMID- 8200641 TI - Frequency and distribution of numerical chromosomal aberrations in prostatic cancer. AB - Prostatic cancer frequently shows striking morphological heterogeneity and multifocal growth. To better understand the relationship between chromosomal changes and pathological characteristics, 31 routinely processed radical prostatectomy specimens were studied for the presence of numerical chromosomal aberrations by in situ hybridization with centromeric nucleic acid probes specific for chromosomes 7, 10, 17, X, and Y. In 24 of the cases preoperative core biopsy specimens were available and were examined with the probe for the X chromosome. In eight of the prostatectomy specimens chromosome numbers consistent with a normal male karyotype were found. Three cases, besides diploid chromosome numbers, showed a focal doubling of hybridization signals, consistent with tetraploidy. The other 20 cases displayed numerical chromosomal aberrations to a various degree. In this group the appearance of numerical chromosomal aberrations often showed considerable local heterogeneity, generally coinciding with morphological dedifferentiation, and was significantly correlated with tumor stage (P = .0004) as well as primary (P = .0068), worst (P = .0002), and combined (P < .0001) Gleason grades, total tumor volume (P = .0448), and the volume of tumor with Gleason grades 4 or 5 (P < .0001). In four of the 24 core biopsy specimens no residual tumor tissue was left for cytogenetic examination. In the remaining 20 biopsy specimens the presence or absence of numerical changes matched the result obtained on the corresponding prostatectomy specimen. We conclude that in prostatic cancer the presence of numerical chromosomal aberrations is associated with advanced disease. Especially in low differentiated tumors local heterogeneity in 2 chromosome numbers can be very marked. It is possible to forecast the presence or absence of numerical chromosomal changes on preoperative core biopsy specimens. PMID- 8200642 TI - Fine-needle aspiration cytology of ductal hyperplasia with and without atypia and ductal carcinoma in situ. AB - To determine cytomorphological characteristics of proliferative lesions of breast duct epithelium, we reviewed fine-needle aspiration (FNA) smears of 11 cribriform and micropapillary, low nuclear grade, ductal carcinomas in situ (DCIS), nine atypical ductal hyperplasias (ADH), and 10 florid or moderate ductal hyperplasias (DH) without atypia. These breast lesions presented as a palpable mass in 16 patients or were detected by diagnostic imaging in 14 patients. Cytological findings evaluated were cellularity, cell composition, architectural pattern (including presence and shape of intercellular spacing and cell characteristics of epithelial cell groups), nuclear diameter and pleomorphism, chromatin pattern, and number of single epithelial cells. Smears also were evaluated by cytological criteria only, using the scoring system of Masood et al. Based on our study's use of cytological and architectural features combined, the FNA diagnoses were as follows: of the 11 DCIS cases eight were carcinoma and three were inconclusive: proliferative epithelium (ADH v DCIS); of the nine ADH cases two were carcinoma and seven were inconclusive: proliferative epithelium (ADH v DCIS); and of the 10 DH cases four were DH, two were suspicious for carcinoma, and four were inconclusive: proliferative epithelium (DH v ADH). Using the cytological scoring system alone, of the 11 DCIS cases one was classified as carcinoma, five as ADH, and five as DH; of the nine ADH cases one was classified as carcinoma, three as ADH, and five as DH; and of the 10 DH cases four were classified as ADH and six as DH. This study shows that the application of both cytological and architectural criteria to the interpretation of FNA smears is more reliable than cytology alone in the identification of proliferative breast lesions and low grade carcinoma. However, overlapping features between DH and ADH as well as ADH and low-grade carcinoma exist making separation of some of these lesions difficult. Aspirates of DH and ADH may display many single epithelial cells, mimicking low-grade carcinoma. However, a diagnosis of low-grade carcinoma can be made with confidence if the aspirates are cellular with many single atypical epithelial cells and lack an admixture of benign cellular elements. Architectural and cytological characteristics of proliferative duct epithelium, as evaluated in histological sections, are well represented in aspiration smears and should aid in the identification of these lesions. PMID- 8200643 TI - Is submission of remaining tissue necessary when incidental carcinoma of the prostate is found on transurethral resection? AB - We examined 151 entirely submitted transurethral resection of the prostate (TURP) specimens that showed incidental prostate cancer. Fifty-one (34%) showed > 15% involvement of the specimen by tumor; these were not reviewed because submission of more tissue would not convert these cases from stage T1b (> or = 5% of tumor) to stage T1a ( < 5% of tumor). Sixty-six cases (44%) that were totally submitted in < or = nine cassettes also were excluded because most laboratories would totally submit these specimens from the outset. The remaining 34 cases (22%) had < or = 15% tumor and required 10 or more cassettes for total submission. The first eight slides were reviewed and percentage of tumor involvement and grade was calculated. The remaining slides were then reviewed to see if the overall tumor percentage or grade changed. Because in one case the tumor grade was significantly increased in the remaining slides and of the infrequency with which more than eight cassettes needs to be submitted, we recommended submission of all remaining tissue in stage T1a lesions. There is no need to submit additional tissue in stage T1b lesions because the percentage will not decrease with greater sampling. PMID- 8200644 TI - From Dukes through Jass: pathological prognostic indicators in rectal cancer. AB - In the recently described Jass staging system for resected adenocarcinoma of the rectum, peritumoral lymphocytic infiltration and tumor growth pattern are introduced as significant indicators of prognosis in conjunction with depth of tumor invasion and lymph node metastasis. The authors of this study have tested the applicability of the Jass system by reviewing 348 resected rectal cancers for 12 pathological variables, including two newly recognized features, namely the Crohn's-like lymphoid reaction and metastatic tumor nodules in pericolic fat. By univariate analysis improved 5-year survival rate was associated with tubular type adenocarcinoma, low tumor grade, retention of tubule configuration and nuclear polarity, expanding tumor growth pattern, prominent peritumoral lymphocytic infiltration, absence of extramural vein invasion by tumor, all levels of intramural and extramural invasion short of widespread local tumor dissemination, a Crohn's-like lymphoid reaction pattern, and absence of both nodal metastasis and tumor nodules in perirectal fat. By Cox stepwise proportional hazards analysis, depth of tumor invasion, lymph node metastasis, Crohn's-like lymphoid reaction, and extramural venous invasion retained independent prognostic significance. Peritumoral lymphocytic infiltration and tumor growth pattern of the Jass staging system failed to compete successfully with other variables in the proportional hazards model, in part because of their correlation with the model's selected variables. Both intramural and extramural extent of tumor invasion coupled with lymph node metastasis form the cornerstones of rectal cancer staging. However, other factors do refine prognostication. From this study the Crohn's-like lymphoid reaction emerges as a significant new independent indicator of prognosis for survival from rectal cancer. Although the Crohn's-like lymphoid reaction and extramural vein invasion took precedence as staging variables in this study, a complex interrelationship with other parameters was observed. PMID- 8200645 TI - Comparison of DNA ploidy in prostatic intraepithelial neoplasia and invasive carcinoma of the prostate: an image cytometric study. AB - Prostatic intraepithelial neoplasia (PIN) is regarded as the most important premalignant lesion of prostatic epithelium. The aim of this investigation was to find clues to formal pathogenesis of prostatic cancer. For this purpose DNA ploidy (determined by means of image cytometry [ICM] using 4-microns-thick Feulgen-stained paraffin sections) of PIN and invasive carcinoma was compared. Prostatic tissue of 72 patients (mean age, 67.5 years; 82 areas with carcinoma and 71 areas with PIN) was examined. In 44 cases PIN and carcinoma were coexistent in the same prostates, the PIN grade being high in 77% of these cases (P < .05). In higher-grade PIN and higher-grade carcinoma the c-values, 2.5c exceeding-rate, and aneuploidy rate increased (P < .01). Carcinomas associated with diploid PIN (either low or high grade) showed diploidy and aneuploidy in an equal number of cases, whereas 70% of aneuploid PIN cases (all high grade) were associated with aneuploid invasive carcinomas (P < .01). Conversely, in 71% of the cases with aneuploid carcinoma the coexistent PIN (either low or high grade) was diploid. Our findings show that aneuploidy can be acquired at a preinvasive stage of carcinogenesis in the prostate and suggest that aneuploid high-grade PIN might be regarded as a precursor of some but not all aneuploid prostatic carcinomas. Image cytometry analysis seems to be a promising method for further subclassification of high-grade PIN lesions into groups with putatively lower or higher risk. However, further investigation is necessary to confirm the clinical importance of these results. PMID- 8200646 TI - C-cell hyperplasia associated with chronic lymphocytic thyroiditis: a retrospective quantitative study of 112 cases. AB - Since the first description by Wolfe et al of C-cell hyperplasia (CCH) in asymptomatic relatives of patients suffering from a medullary thyroid carcinoma (MTC), several investigators have described CCH associated with a chronic lymphocytic thyroiditis (CLT) not within the context of MTC or multiple endocrine neoplasia (MEN). We report the study of C-cell density in 112 cases of CLT on retrospective surgical material to determine the frequency of the association between CCH and CLT. The cases of CLT were compared with 19 normal thyroid glands obtained at necropsy. C cells, immunoreactive with a polyclonal anti-calcitonin (CT) antibody, were counted at high magnification (X400) and the number of low power magnification (X100) microscopic fields (LPFs) containing at least 50 C cells per slide was assessed. Image analysis was performed to determine the C cell density expressed in number of C cells/cm2. C-cell hyperplasia was defined by the following criteria: C-cell density > 40 cells/cm2 and the presence of at least three LPFs containing more than 50 C cells. Twenty percent of the cases of CLT showed a CCH thus defined, and four of them had an elevated serum CT level. Statistical analysis showed no clinical or biological correlation with the presence of CCH. However, the frequency of CCH was higher if a follicular cell carcinoma was associated with CLT. This study confirms a pathological association between CCH and CLT, provides new criteria for the definition of CCH on surgical pathology material, and reports four cases with an elevated serum CT level not within the context of MTC or MEN. PMID- 8200648 TI - Can immunohistological analysis of transbronchial biopsy specimens predict responder status in early acute rejection of lung allografts? AB - Acute cellular rejection (ACR) in the early posttransplant period is recognized as one predictor of the development of bronchiolitis obliterans in lung transplant recipients. Using an immunohistochemical panel of antibodies to CD3, L26, HLA-DR, collagenase IV, proliferating cell nuclear antigen (PCNA), KPI, and S100 antigens we analyzed cases of moderate ACR that did respond (n = 11) and that did not respond (n = 10) to bolus solumedrol therapy early in the postoperative period (< 100 days) to determine if we could identify predictors of histological response. Responders who had follow-up negative biopsies after therapy had biopsy specimens containing an average of 41.1% T cells (range, 15.1 to 69.8), 8.8% B cells (range, 0.6 to 20), 18.1% HLA-DR-positive cells (range, 3 to 29.6), 12.2% PCNA-positive cells (range, 2.7 to 22.6), 8.9% collagenase IV positive cells (range, 0.7 to 20.9), and rare dendritic cells. Nonresponders who had follow-up biopsies that failed to show a significant change in rejection grade had biopsy specimens with the following average cell profiles: 35.8% T cells (range, 7 to 70.7), 21.6% B cells (range, 3.7 to 39.5), 14.2% HLA-DR positive cells (range, 1.8 to 24.7), 11.4% PCNA-positive cells (range, 0.8 to 22), 12.6% collagenase IV-positive cells (range, 0.6 to 34.1), and occasional dendritic cells. Statistical analysis suggested that large numbers of B lymphocytes in early acute rejection predicts non-responsiveness to interventional immunosuppressive therapy and may indicate a significant role of humoral rejection in the behavior of early allograft rejection. PMID- 8200647 TI - Ber-H2 expression in testicular germ cell tumors. AB - Expression of CD30 antigen using the monoclonal antibody Ber-H2 was investigated in 52 testicular tumors: pure seminoma (19 cases), pure embryonal carcinoma (eight cases), and mixed germ cell tumors (25 cases). None of the seminomas expressed Ber-H2, whereas seven of eight pure embryonal carcinomas contained this antigen. In mixed germ cell tumors Ber-H2 was present in none of 10 seminomatous components, none of seven yolk sac tumor components, and 20 of 24 embryonal carcinoma components. Teratomatous elements (16 cases) failed to stain with Ber H2. Also, foci of intratubular germ cell neoplasia (ITGCN) (31 cases) failed to express Ber-H2. Ber-H2 is useful in distinguishing embryonal carcinoma from seminoma and yolk sac tumor. The failure of expression of Ber-H2 in ITGCN, as in seminoma, supports the close relationship of seminoma with ITGCN. PMID- 8200649 TI - Immunolocalization of aromatase and other steroidogenic enzymes in human breast disorders. AB - Numerous studies have shown that human breast cancer tissue has the potential to synthesize estrogen through aromatization, which may act as a local growth factor of hormone-dependent cancer cells. This study was performed to localize the site of aromatization in human breast disorders by immunohistochemistry and correlate the findings with steroid receptors, clinicopathological findings, and other steroidogenic enzymes. Specimens from 60 cases of breast disorders, including 33 cases of breast cancer and 27 cases of benign proliferative disorders, were studied immunohistochemically for aromatase. In the carcinoma cases estrogen receptor (ER) and progesterone receptor (PgR) status was determined by enzyme immunoassay and immunohistochemistry, and other steroidogenic enzymes, including P450scc (side-chain cleavage), 3 beta HSD (hydroxysteroid dehydrogenase), and P450c17, were immunolocalized. Aromatase was immunolocalized in interstitial cells and adipocytes as well as other cells in both benign and malignant breast tissues. However, strong immunoreactivity was observed in adipocytes adjacent to carcinoma in all carcinoma cases and in interstitial or stromal cells around carcinomatous glands in 20 carcinoma cases. Intratumoral staining for aromatase did not correlate significantly with age, clinical stage, histopathological type, lymph nodes metastasis, or ER and PgR status. P450scc and 3 beta HSD were focally observed in 18 and 12 cases of carcinoma, respectively, but P450c17 was never observed. Aromatase expression in stromal or interstitial cells, including adipocytes, in breast cancer may be induced by carcinoma cells and locally synthesized estrogens could function as paracrine hormones. Intratumoral aromatase in human breast neoplasms correlated with malignant phenotypes but not with ER status or prognostic parameters, suggesting that other synthetic systems probably generate any biologically significant locally synthesized estrogens in hormone-dependent breast malignancy. PMID- 8200650 TI - Squamous cell papillomas of the esophagus: a study of 23 lesions for human papillomavirus by in situ hybridization and the polymerase chain reaction. AB - This study assessed squamous cell papillomas of the human esophagus for the presence of human papillomavirus (HPV) and correlated the results with histological features. Twenty-three lesions obtained by endoscopic biopsy from 17 patients were studied, first by in situ hybridization (ISH) for HPV types 6-11, 16-18, 18, and 31-33-51, and second by the polymerase chain reaction (PCR) with amplification of multiple HPV types and demonstration of amplified product by ethidium bromide staining and Southern blot hybridization for HPV types 6-11, 16, and 18 in each case. Evidence of HPV DNA was found in only one lesion, which showed HPV type 6-11 by ISH and HPV positivity by Southern blotting of the amplified product after the PCR. This case exhibited histological features suggestive of HPV infection, although no morphological changes specific to the lesion were identified. The remaining 22 lesions, including those from cases in which multiple papillomas were present, were negative for HPV. The results show that HPV DNA is frequently not detectable in esophageal squamous cell papillomas, even when highly sensitive techniques are used. These findings are consistent with the hypothesis that other pathogenetic mechanisms, such as mucosal injury and repair, are important in the etiology of these lesions. PMID- 8200651 TI - Multiple myeloma after cardiac transplantation: an unusual form of posttransplant lymphoproliferative disorder. AB - Published reports of posttransplant myeloma are extremely uncommon (three cases); to the best of our knowledge there have been no reported cases in cardiac transplant recipients. We are also unaware of any report of Epstein-Barr virus (EBV) genome studies in posttransplant myeloma. We report here the case of a 48 year-old man who developed multiple myeloma 1.5 years after cardiac transplantation. The results of a serum analysis were consistent with past EBV infection. Biopsy of a skull lesion showed a monomorphous population of malignant immature plasma cells that showed monotypic cytoplasmic staining with antibodies to lambda light chains. A monoclonal immunoglobulin heavy chain gene rearrangement was detected by polymerase chain reaction (PCR). Both EBER-1 in situ hybridization and EBNA-1 PCR were negative for the EBV genome. Cyclosporin withdrawal was followed by transient clinical and biological improvement, but the tumor later progressed and eventually stabilized in response to treatment with dexamethasone alone. This case illustrates that posttransplant lymphoproliferative disorders (PTLPDs) encompass not only EBV-positive but also EBV-negative cases and not only lymphomas but also myelomas. PMID- 8200652 TI - Hyperostosis cranii ex vacuo: a rare complication of shunting for hydrocephalus. AB - Hyperostosis cranii ex vacuo is a condition that may develop after successful ventricular shunting for hydrocephalus. It is characterized by diffuse thickening of the skull (particularly the inner table) involving the calvarium and the base. It is a diagnosis that distinguishes marked calvarial thickening from thickening of the skull because of other causes. It is an entity that needs to be considered in patients who have diffuse thickening of the skull, have premature closure of sutures, and who have been treated for hydrocephalus in the past. PMID- 8200653 TI - FDA device approval regulations. PMID- 8200654 TI - Monoclonal antibodies to glioma-derived growth factor(s). AB - Several monoclonal antibodies (mAb) reactive against a high-molecular-weight growth factor from human glioblastoma cell lines have been produced by immunizing mice with partially purified preparations from conditioned media. Antibody secreting colonies were selected by their capacity to bind 35S-labeled glioma cell protein and by reactivity in indirect enzyme-linked immunoadsorbent assay (ELISA), using high-molecular-weight gel filtration fractions and preparative isoelectric focusing fractions containing growth factor activities. Two of the select mAbs (20F3 and 12A12) depleted mitogenic activity (> 50% inhibition, p < 0.05) from gel filtration fractions by immunoprecipitation, but could not neutralize mitogenic activity directly. Mitogenic activity recovered from affinity columns prepared with mAb 20F3 eluted at 48% and 52% acetonitrile from HPLC C4 reversed-phase columns. Immunoprecipitation of 35S-labeled cell lysates with 20F3 followed by resolution with SDS-PAGE autoradiography revealed one unique protein of 170 kD. Established glioma cell line D-54 MG showed perinuclear and cytoplasmic staining with mAb 20F3. mAb 20F3 should prove useful in purification and characterization of these glioma-derived growth factor(s). PMID- 8200657 TI - Monoclonal antibodies to mammalian D-type G1 cyclins. AB - D-type cyclins are necessary and rate-limiting for G1 progression during the mammalian cell cycle. Cyclins D1, D2, and D3 are encoded by distinct genes and are expressed in proliferating cells in a lineage-specific manner. Monoclonal antibodies (mAbs) generated to bacterially produced recombinant D-type cyclins were able to react with the native proteins expressed in mammalian cells. One mouse and three rat mAbs immunoprecipitated cyclin D1 from mouse macrophages. Only rat mAbs reacted with human cyclin D1 and cross-reacted with cyclin D2 expressed in proliferating T lymphocytes and human tumor cell lines. A single rat mAb to cyclin D2 exhibited a pattern of reactivity reciprocal to that of rat mAbs to D1. Three rat mAbs reacted specifically with mouse or human cyclin D3, but did not cross-react with cyclins D1 or D2 from either species. Representative mAbs were useful for immunoblotting and detected D-type cyclins coprecipitating in complexes recovered with antiserum to cyclin-dependent kinase-4 (CDK4). Because these mAbs detect D-type cyclins in the nuclei of fixed permeabilized cells, they should prove useful in documenting cyclin overexpression in those human tumors in which the genes are amplified or are targets of specific chromosomal rearrangements. PMID- 8200655 TI - Production and characterization of new murine monoclonal antibodies reactive to Mycobacterium tuberculosis. AB - Murine monoclonal antibodies were raised against Mycobacterium tuberculosis (H37Rv) employing conventional hybridoma procedure. The binding characteristics of the four selected monoclonal antibodies reactive to M. tuberculosis were assessed by enzyme-linked immunosorbent assay (ELISA) using sonic extracts. The immunofluorescence test (IFT) was done using intact M. tuberculosis, 16 other mycobacterial species, and 10 bacteria of other genera. Monoclonal antibody A30 reacted strongly to M. tuberculosis both in ELISA and IFT. Monoclonal antibody A25 showed restricted cross-reactivity with mycobacterial species whereas two other monoclonal antibodies B6 and H2 appeared broadly cross-reactive. In Western blot analysis, A30 reacted with the 30-kD protein antigen, A25 with the 18- and 28-kD protein bands, H2 with the 18-kD antigen alone, and B6 with three bands of 17-19, 22, and 28 kD of M. tuberculosis H37Rv. A30 exhibited high reactivity with virulent M. tuberculosis H37Rv and a clinical South Indian Strain and minimal reactivity with avirulent M. tuberculosis H37Ra strain. PMID- 8200656 TI - Production of IgG monoclonal antibodies to the tumor-associated antigen, CA-195. AB - The isotype of a monoclonal antibody is closely associated with its biologic activity. Certain immunoglobulin subclasses are more effective than others regarding their ability to execute complement-mediated lysis of cells, antibody dependent cell-mediated cytotoxicity, and tumor localization. Many potential targets for cancer immunotherapy are tumor-associated antigens with high percentages of carbohydrate. Immunizations of mice with carbohydrate antigens usually produce IgM and IgG3 antibodies. The use of different adjuvants in immunization protocols has been associated with the induction of isotype-specific antibody responses. In experiments reported here, we compare the use of four different adjuvants on the generation of an IgG immune response to the carbohydrate-rich, tumor-associated antigen, CA-195. We report the production of IgG1 and IgG2a monoclonal antibodies (mAbs) to CA-195. PMID- 8200659 TI - Influence of priming and inoculation dose on the production of monoclonal antibodies in two age groups of BALB/c mice. AB - An experiment was set up to assess the influence of some parameters on the production of ascites and monoclonal antibodies against circulating excretory secretory antigens of Taenia saginata cysticerci in mice. The following parameters were examined: time lapse between priming and the inoculation of hybridoma cells, age and body weight of the mice at the time of inoculation, number of cells injected IP, and the resulting antibody titers of the ascites. In this experiment the method used to prime the mice was the only factor having an influence on the amount of ascites produced. Injection of a higher number of hybridoma cells (2-4 x 10(6) cells) coincided with higher antibody titers and resulted in an earlier ascites production. The antibody titer of the ascites was increasing with time. PMID- 8200658 TI - Production of monoclonal antibodies against the outer cell wall of Clostridium tyrobutyricum. AB - Several hybridoma cell lines producing murine monoclonal antibodies (mAbs) directed to the Clostridium tyrobutyricum outer cell wall have been established and characterized. Whole bacteria, crude extract of cell wall, and polysaccharide fraction of crude extract have been used as immunogens. The immunizations were performed either in vivo or in vitro after priming in vivo. Amongst the clones obtained, six hybridoma cell lines were selected. Four mAbs recognized only the immunizing strain (ATCC 25755), while two mAbs recognized all the C. tyrobutyricum tested strains. Three mAbs were IgM, one IgG3, and two IgG1 isotypes. The antigens (proteins or polysaccharides) recognized by these mAbs have been characterized by Western Blot. These mAbs could be used for an early detection of C. tyrobutyricum in milk. PMID- 8200660 TI - Immunization of mice by injection with a recombinant retrovirus vector containing human factor IX for production of monoclonal antibody against factor IX. AB - A novel immunization procedure for eliciting murine monoclonal antibodies (mAb) is described. A murine leukemia virus (MLV)-based retroviral vector, designed as a marker protein for the expression of human factor IX (FIX), was constructed. Direct injections of mice with 0.8-1.3 x 10(4) retroviruses were carried out three times at 4-week intervals. Three out of 4 mice that had the viruses injected subcutaneously produced the antibodies against FIX, and 2 out of 3 mice injected intraperitoneally produced the antibodies. From 1 of the mice with the antibodies, an anti-human FIX murine monoclonal antibody, designated ACTIX (IgMk type), was produced. The immunization of mice by direct injection of viruses facilitated mAb production in many instances in which cDNAs are available. PMID- 8200661 TI - Detection and characterization of murine ecotropic recombinant virus in myeloma and hybridoma cells. AB - Ecotropic recombinant virus (ERV), a relatively new class of murine retrovirus endogenous to mice, is expressed at significant levels by most murine myeloma and hybridoma cells examined. The routine XC, S+L-, mink cell focus-inducing (MCF), and reverse transcriptase (RT) tests are not suitable to detect and quantify the levels of ERV. A serological focus assay, based on specific anti-murine leukemia virus (MuLV) viral envelope (env) antibodies, is required to detect ERV. A more sensitive format of this serological focus assay includes co-cultivation of test article cells with the indicator (Mus dunni) cells. ERV isolated from murine hybridoma cells show a unique pattern of cross-reactivity with anti-MuLV env antibodies and this pattern is clearly distinct from that of ecotropic and xenotropic retroviruses. PMID- 8200662 TI - Uniqueness of the generators of brain evoked potential maps. AB - This study considers the uniqueness of neuronal generators of human brain evoked potentials measured on the scalp using the physical and mathematical properties of the volume conductor model. The results are applicable to a realistic, nonhomogeneous head shape where the potential map is known on a continuous set of points on the scalp. It is shown that sources which occupy "zero volume" in space such as point dipoles or sources distributed on an open surface or a line are uniquely defined by the potential maps. Finite volume nonoverlapping sources are also uniquely defined by their potential map. However, there are infinitely many different but overlapping sources which can create the same map. Several examples of such sources are provided. It is shown that there is a unique, minimum volume source which can be defined in this case. Results suggest that if a reconstruction of the sources starts from a continuous scalp map (obtained by interpolation of the data between electrode sites), one can obtain unique results concerning the source parameters that are not available in a search for a source whose potential map fits only at a discrete set of points. PMID- 8200663 TI - Binaural hearing in the presence of a low frequency magnetic field. AB - We propose the binaural auditory system as a candidate neural system that may be disrupted by exposure to relatively weak LF magnetic fields. Extracellular currents, induced by time-varying magnetic fields, may change the timing of action potentials in the auditory nerve, thereby disrupting sound localization when interaural time differences are very small. Three subjects were exposed to a 1000 Hz magnetic field--with a maximum rate of change of 2.3 T/s at the location of the cochlea--while presenting two identical 1000 Hz tones randomly delayed to the left or right ear by less than 10 microseconds. The subjects were asked whether the signal was perceived to be displaced to the left or right side of midline. After a total of over 20,000 trials, conducted at different phase angles between the field signal and the tones, there was no clear evidence for a consistent change in performance when the magnetic field was present. This, however, does not rule out an effect at other combinations of magnetic and acoustic frequencies. PMID- 8200664 TI - Practical induction heating coil designs for clinical hyperthermia with ferromagnetic implants. AB - Interstitial techniques for hyperthermia therapy of cancer continue to evolve in response to requirements for better localization and control over heating of deep seated tissues. Magnetic induction heating of ferromagnetic implants is one of several available techniques for producing interstitial hyperthermia, using thermal conduction to redistribute heat within an array of controlled temperature "hot sources." This report describes seven induction heating coil designs that can be used for producing strong magnetic fields around ferromagnetic seed implants located in different sites in the body. The effect of coil design on the extent and uniformity of the magnetic field is characterized, and appropriate electrostatic shield designs for minimizing electric field coupling to the patient are described. Advantages and disadvantages of each coil type are discussed in terms of the radiated fields, coil efficiency, and ease of use, and appropriate applications are given for each design. This armamentarium of induction coils provides the ability to customize magnetic field distributions for improved coupling of energy into ferromagnetic implant arrays located at any depth or orientation in the body. Proper selection of heating coil configuration should simplify patient setup, improve the safety of patient treatments, and pave the way for future applications of interstitial heating in sites that were previously untreatable. PMID- 8200665 TI - High frequency ultrasonic backscatter from erythrocyte suspension. AB - Previous studies have shown that ultrasonic backscattering from red blood cells suspended in saline is proportional to the fourth power of frequency for frequencies below 15 MHz, as predicted by Rayleigh scattering theory. Recently, we have extended the measurements up to 30 MHz, because scattering of ultrasound by red blood cells may no longer be negligible at these frequencies and can affect, to a great degree, the operation of intravascular imaging devices. The experimental results show that the fourth power dependence on frequency of the backscattering coefficient for porcine erythrocytes suspended in saline solution appears to be valid up to 30 MHz. To confirm this, backscattering cross-section of porcine red cells was computed as a function of frequency using the T-matrix method. Since at higher frequencies the shape of the scatterers may also play a significant role, its effect was investigated by treating the red cell as a sphere, a disc, and a biconcave disc of the same volume. Good agreement was obtained between the experimental and theoretical results. PMID- 8200666 TI - Pulse Doppler ultrasound detection, characterization and size estimation of emboli in flowing blood. AB - A theory describing pulse Doppler ultrasound signals due to backscattering due to emboli in flowing blood is presented. From this theory, the minimum detectable size of a formed-element embolus can be established as a function of carrier frequency and vessel size. Emboli can be sized and characterized, based on the ratio of the amplitude of the Doppler signal during embolus passage through the sample volume to background bloodflow Doppler signal when no embolus is present. This ratio is defined as the "embolus to blood ratio" (EBR). Size estimation of emboli can be done by insonating an embolus with a single frequency and measuring the EBR, only if the embolus does not exceed a certain size, and if the vessel diameter and per cent hematocrit are known. Using two different frequencies, the vessel geometry (diameter and sample volume length) and per cent hematocrit can be eliminated from calculation of embolus size. Sources of uncertainty in the EBR and their effect on embolus size estimation are discussed. Discrimination between gas and formed-element emboli is described, given a detector with sufficient dynamic range, and use of three carrier frequencies. The theory presented here is in agreement with experimental findings of other investigators. PMID- 8200667 TI - A fiber optic system for measuring dynamic mechanical properties of embryonic tissues. AB - Dynamic mechanical properties of embryonic tissues, including viscoelasticity and active motility, play a major role in morphogenesis. Mechanical abnormalities resulting from altered cytoskeletal chemistry presumably contribute to spina bifida and other birth defects, but research in this area has been limited by inadequate mechanical measurement techniques. This paper discusses aspects of embryo tissues that make them difficult to measure and describes a versatile new system developed and used to study the biomechanics of morphogenesis in amphibian embryos. It incorporates a flexible optical-fiber probe driven by piezoceramic elements to impose and measure feedback-controlled, two-dimensional, time-varying patterns of stress or strain in the tissue. Compression, tension, and shear geometries are possible. Capacitive displacement sensors provide the precision and low drift rates required for these measurements. Software control permits the system to perform both standard and customized rheological tests, including interactive ones in which test parameters change in response to measured tissue behavior. Sample size range is 50 microns to 5 mm. Displacement range is 60 microns with a resolution of 0.1 microns. Force range is 10 microN with a resolution of 0.02 microN. Frequency range is DC to 20 Hz. PMID- 8200668 TI - An adaptive lung ventilation controller. AB - Closed loop control of ventilation is traditionally based on end-tidal or mean expired CO2. The controlled variables are the respiratory rate RR and the tidal volume VT. Neither patient size or lung mechanics were considered in previous approaches. Also the modes were not suitable for spontaneously breathing subjects. This report presents a new approach to closed loop controlled ventilation, called Adaptive Lung Ventilation (ALV). ALV is based on a pressure controlled ventilation mode suitable for paralyzed, as well as spontaneously breathing, subjects. The clinician enters a desired gross alveolar ventilation (V'gA in l/min), and the ALV controller tries to achieve this goal by automatic adjustment of mechanical rate and inspiratory pressure level. The adjustments are based on measurements of the patient's lung mechanics and series dead space. The ALV controller was tested on a physical lung model with adjustable mechanical properties. Three different lung pathologies were simulated on the lung model to test the controller for rise time (T90), overshoot (Ym), and steady state performance (delta max). The pathologies corresponded to restrictive lung disease (similar to ARDS), a "normal" lung, and obstructive lung disease (such as asthma). Furthermore, feasibility tests were done in 6 patients undergoing surgical procedures in total intravenous anesthesia. In the model studies, the controller responded to step changes between 48 seconds and 81 seconds. It did exhibit an overshoot between 5.5% and 7.9% of the setpoint after the step change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200669 TI - Refractory period prolongation by biphasic defibrillator waveforms is associated with enhanced sodium current in a computer model of the ventricular action potential. AB - Mechanisms through which biphasic waveforms lower defibrillation threshold are unknown. Previous work showed that low-intensity biphasic shocks (BS2), delivered during the refractory period of a control action potential (S1), produced significantly longer responses than monophasic shocks (MS2). To test the hypothesis that longer responses are due to hyperpolarization-induced excitation channel recovery during the first portion of the biphasic waveform, we used the Beeler-Reuter ventricular action potential computer model with the Drouhard Roberge (BRDR) modification to study refractory period stimulation with MS2 (10 msec) and symmetrical BS2 (10 msec each pulse). At 1.5 times diastolic threshold, BS2 prolonged action potential duration when delivered 50 msec into the S1 refractory period, and produced a maximum BS2 versus MS2 response duration difference of 62 msec. Longer BS2 responses corresponded to enhanced BS2-induced sodium current compared to MS2. Maximum BS2 vs MS2 sodium current difference was 400 uA/cm2. These results show that, in a computer model of the ventricular action potential, hyperpolarization by the first phase of a biphasic waveform enhances S2 sodium current and prolongs duration of refractory-period responses. This effectively shortens the cellular refractory period. Prolonged refractory period responses, produced by biphasic defibrillator waveforms, may underlie enhanced defibrillating efficacy at low shock intensities. PMID- 8200670 TI - Transfer-function analysis of UFCT myocardial time-density curves by time-varying recursive least squares analysis. AB - Techniques which assume linear, time-invariant systems have been used to characterize indicator dilution pairs. As a basis for fully describing the relation between left ventricular (LV) and myocardial (MYC) time-density curves, produced by an intravenous contrast medium as measured by ultrafast CT, the assumption of time invariance was tested using recursive least squares regression and CUSUM, a test for time variability of regression parameters. Using data from anesthetized dogs with concomitant microsphere information, constant and time varying regression models, MYC(t) = b(t)LV(t-1), were generated from time-density curves of flows from two groups: Group 1 (MBF < 2 ml/min/gm, n = 11) and Group 2 (MBF > 2 ml/min/gm, n = 10). The time-varying regression models had reduced root mean square error: 0.6 +/- 1.1 and 0.5 +/- 0.8 versus 7.3 +/- 3.5 and 4.1 +/- 1.6 for Groups 1 and 2, respectively. Significant time variability (p < 0.05) by CUSUM was found in 9/11 Group 1 models and 7/10 Group 2 models. Myocardial blood volume was estimated as the average value of b(t) over the rising portion of the LV curve. Myocardial blood flow was then calculated as myocardial blood volume divided by coronary transit time, determined from gamma variate fits of the LV and scaled, shifted LV curve, with excellent results over a wide range of flows (r = 0.93, y = 0.92 x + 0.28, range of 0.4 to 6.7 ml/min/gm). These results show that measurements of increased myocardial blood flow are possible with an intravenous contrast media, and that movement of contrast medium from intravascular space to extravascular space occurs during the course of the contrast medium's first pass. PMID- 8200671 TI - Time-frequency digital filtering based on an invertible wavelet transform: an application to evoked potentials. AB - This paper presents a method to analyze and filter digital signals of finite duration by means of a time-frequency representation. This is done by defining a purely invertible discrete transform, representing a signal either in the time or in the time-frequency domain, as simply as possible with the conventional discrete Fourier transform between the time and the frequency domains. The wavelet concept has been used to build this transform. To get a correct invertibility of this procedure, we have proposed orthogonal and periodic basic discrete wavelets. The properties of such a transform are described, and examples on brain-evoked potential signals are given to illustrate the time-frequency filtering possibilities. PMID- 8200672 TI - Classification of action potentials in multi-unit intrafascicular recordings using neural network pattern-recognition techniques. AB - Neural network pattern-recognition techniques were applied to the problem of identifying the sources of action potentials in multi-unit neural recordings made from intrafascicular electrodes implanted in cats. The network was a three-layer connectionist machine that used digitized action potentials as input. On average, the network was able to reliably separate 6 or 7 units per recording. As the number of units present in the recording increased beyond this limit, the number separable by the network remained roughly constant. The results demonstrate the utility of neural networks for classifying neural activity in multi-unit recordings. PMID- 8200675 TI - Older widows' experience of living alone at home. AB - Older widows' experience of living alone is described in this research. Based on Husserl's (1913/1962) philosophy, a phenomenological method was used. Prior to data-gathering, knowledge pertaining to older widows' experience was bracketed. During semi-structured, tape-recorded conversations, seven older widows described how they lived at home alone. From data pertaining to their actions, intentions and perceptions, four phenomena of the lived experience were developed: (a) making aloneness acceptable; (b) going my own way; (c) reducing my risks; and (d) sustaining myself. PMID- 8200676 TI - Evaluating therapeutic change in symptom severity at the level of the individual woman experiencing severe PMS. AB - Treatment effectiveness of an intervention designed for women experiencing severe Premenstrual Syndrome (PMS) was assessed at the level of the individual woman since patterns of individual response are of most relevance to practitioners. Symptom severity was evaluated daily in five women across seven menstrual cycles using a time-series methodology. Three symptom severity patterns emerged from the baseline data analysis: a "classic" PMS pattern, a premenstrual magnification pattern and a social week pattern. Patterns of therapeutic response emerged from the time-series analysis of post-treatment data compared with baseline symptom severity patterns: a "normalized" response pattern where symptom severity declined to a mild, cyclic process and an "unstable" response pattern that remained reactive. Treatment effects for menstrual cycle phenomena may be evaluated using the "normalizing" or "unstable" patterns as clinical indicators. PMID- 8200673 TI - Ultrasound scattering from blood with hematocrits up to 100%. AB - The backscattering coefficient of saline suspensions of porcine red blood cells was measured for hematocrits up to about 90%. It was found that the coefficient peaks at approximately 15%, but then, contrary to what a simple "gap theory" might suggest, it decays smoothly to zero, without showing another peak at high hematocrits. A one-dimensional (1-D) slab scattering model, in which the number of slabs per unit length represents the hematocrit and whose thickness and acoustical properties are similar to red cells/plasma, was also used to investigate the relation between the backscattered power and hematocrit. Monte Carlo simulations performed for randomized boundary conditions show a similar relation to that of the 3-D system. The experimental data is compared to the Percus-Yevick theory for the packing of hard spheres, and the simulated data is compared to the Percus-Yevick theory for infinite slabs. PMID- 8200674 TI - An assessment of Arab American knowledge, attitudes, and beliefs about AIDS. AB - An important component of an effective AIDS prevention program is the dissemination of relevant information concerning AIDS risk behaviors. The purpose of this study was to identify the knowledge, attitudes, and beliefs of 411 randomly selected Arab Americans. The results indicate a low level of self assessed knowledge about AIDS, a high number of misconceptions about the transmission of HIV, and a high level of anxiety about HIV infection. PMID- 8200677 TI - The incidence of reporting consent rates in nursing research articles. AB - The study described the incidence of reporting consent rates (CRs) in nursing research articles, ascertained the mean CR for nursing research articles, ascertained differences between those studies that reported a CR and those that did not report a CR, and compared studies that used clinical populations to studies that used nonclinical populations. Research articles (371) from three nursing research journals were examined. Results showed that: (a) 40.7 percent of articles reported a CR, (b) the mean CR was 71.8 percent, (c) 41.1 percent reported inadequate CRs, (d) studies reporting a CR differed from those that did not on five of nine variables, and (e) studies employing clinical populations reported higher consent rates than did studies that employed nonclinical populations. PMID- 8200679 TI - The ethic of care: a comparison of nursing and medical students. AB - The purpose of this research was to examine whether "caring" uniquely reflects the moral orientation of nursing students. Gilligan's theory of moral development and Kolhberg's theory of moral development structured this study of 119 nursing and medical students who described a real-life moral dilemma and responded to a hypothetical clinical moral dilemma. The findings suggest that nursing students use care more than justice considerations, but their moral orientation could best be described as mixed. Differences were found between nursing and medical students, but these differences appeared to be related to gender, not professional role. Therefore, it was concluded that a caring moral orientation is not unique to nursing. PMID- 8200678 TI - Appropriateness of geriatric prescribing decisions made by nurse practitioners and physicians. AB - Legislators' concerns about the ability of nurse practitioners (NPs) to appropriately prescribe medications underlie the regulatory policies governing prescribing in the United States. As a result, state legislation varies concerning whether prescriptive authority is granted to NPs. The prescribing decisions of NPs and physicians were compared using three standardized geriatric case vignettes. NPs scored higher on an index of appropriateness than physicians a difference that remained whether or not the nurse had regulatory support to prescribe. Recommendations are made for more equitable state prescription policies. PMID- 8200680 TI - Identifying types of attending: patterns of nurses' work. AB - Verbal and nonverbal behaviors of nurses during interactions with cancer patients were examined by analyzing videotapes of caregiving. Using techniques of qualitative ethology, four types of attending were identified: doing more, doing with, doing for, and doing tasks. The findings provide support for an alternative method of classifying nurse-patient interactions that captures patterns of caring. PMID- 8200681 TI - Multicultural students' perceptions of nursing as a career. AB - Junior year students (= 276) at a culturally diverse, urban high school were surveyed to examine how their perceptions of nursing compared with their perceptions of an ideal career. Findings indicate that significant differences exist among cultural and racial groups and between genders. Recommendations are made to increase recruitment of multicultural students into nursing. PMID- 8200682 TI - Contributing factors to fear of HIV contagion in registered nurses. AB - This study tested the relationships of homophobia, fear of the unknown, fear of death, and fear of punishment as predictors of fear of HIV contagion. Knowledge of transmission and emotional involvement with a person at risk for HIV were hypothesized as decreasing fear among 114 randomly-selected RNs. Results supported significant relationships for all predictors except fear of death. Homophobia, lack of knowledge, lack of emotional involvement, and fear of the unknown predicted 57 percent of the variance in fear of contagion. PMID- 8200683 TI - Contributions of graduate students to the creation and dissemination of nursing knowledge. AB - The purpose of this study was to determine the extent to which graduate students' research and scholarly activities, as evidenced by publication, contribute to the creation and dissemination of knowledge in nursing. Authors of articles published in IMAGE: Journal of Nursing Scholarship were surveyed to assess their status as graduate students during the conceptualization, development and publication of research or scholarly papers. The sample consisted of 332 authors of manuscripts published in IMAGE from 1986 through 1990. The study design was descriptive. A survey questionnaire elicited data on graduate student status and factors that influenced the initiation and completion of the published work. Descriptive statistical techniques were employed to analyze the data. The results of this study suggest that graduate education in nursing makes an important contribution to the advancement and dissemination of nursing knowledge. PMID- 8200684 TI - Perspectives on the family's caregiving experience in mental illness. AB - Most people with severe mental illness have family members who assist them. This paper explores families' caregiving demands, normative conflicts in family care of mentally ill adults, and changes in the formal care system. It examines the shift in locus of care from institutions to communities. The potential for collaborative models to reduce the burden of caregiving is considered. PMID- 8200685 TI - Gender differences in recovery after coronary artery surgery. AB - Coronary artery bypass surgery is one of the most frequently performed surgical procedures for coronary heart disease, which is the leading cause of illness in American men and women over the age of 50. Since perceptions of events have been shown to significantly affect outcomes after major cardiac illness, it is crucial for nurses to understand patients' perceptions of these events. This article explores how perceptions of cardiac surgery differ considerably by gender and role expectations, and how such differences can influence recovery. PMID- 8200686 TI - Lipid peroxidation, glutathione levels and changes in glutathione-related enzyme activities in streptozotocin-induced diabetic rats. AB - Levels of lipid peroxidation in liver, kidney, brain and blood, liver glutathione (GSH) and several enzymes in liver tissue associated with antioxidant defence mechanism, namely Catalase (EC: 1.11.1.6), GSH reductase (EC:1.6.4.2) and GSH-S transferase (EC: 2.5.1.18), were investigated in streptozotocin-induced diabetic rats. The single intraperitoneal injection of streptozotocin (65 mg/kg) caused a four-, eight- and seven-fold increase in lipid peroxidation in brain, liver and kidney, respectively. A decline in GSH levels both in blood (two-fold) and liver (16%) compared with normal counterparts was also observed. A marginal increase in catalase activity, a 20% decrease in GSH reductase and an increase of GSH-S transferase activity was also found in this experimental diabetic condition. These results suggest experimental diabetes, induced by streptozotocin, can produce biochemical changes not only in pancreas but also in liver, kidney and brain tissue. PMID- 8200687 TI - Development of T cell immune responsiveness in the chicken. AB - Chickens are highly susceptible to infection by opportunistic pathogens during the first few days after hatching. This observation has generally been attributed to an immaturity of the immune system; however, the mechanisms responsible are not known. This study investigated the ability of T cells from chickens of various ages to respond to immune stimulation. Splenic T cells were cultured in vitro and stimulated with various mitogens including Con A, PHA and monoclonal anti-CD3 antibody. T cells obtained from adult chickens proliferated extensively and produced high levels of IL-2, haemopoietic growth factors and IFN following stimulation. In contrast, it was found that T cells from 1 day old chickens failed to proliferate and secrete cytokines when similarly cultured. Reactivity to mitogens gradually developed between days 2 and 4, and by 1 week of age the level of responsiveness was equivalent to that observed with T cells obtained from adult chickens. Whereas T cells from 1 day old chicks were found to be phenotypically mature and capable of binding mitogens as effectively as T cells from adult birds, they were functionally immature as assessed by their inability to proliferate or produce cytokines following immune stimulation. In addition, cells present in the spleen of 1 day old chicks constitutively produced a soluble inhibitor that prevented the proliferation of stimulated adult T cells. The production of inhibitor decreased dramatically by the second day post-hatching which coincided with an enhanced ability of T cells to respond to immune stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200688 TI - Response of peripheral blood leucocytes to mitogenic factor(s) in porcine seminal plasma. AB - Porcine seminal plasma (PSP) contains a potent mitogenic substance capable of causing proliferation and extensive agglutination in cultured porcine peripheral blood leucocytes (PBL). In order to determine the specific leucocyte cell population affected by this mitogen, lymphocyte, monocyte and polymorphonuclear (PMN)-enriched cell fractions were separated from PBL and treated with increasing concentrations of PSP (1-8%, v/v). For monocyte cell populations enriched through elutriation and adherence to plastic, cell proliferation in response to PSP treatment was consistently higher than PSP-treated unfractionated PBL. Monocyte depleted PBL and lymphocyte populations enriched through elutriation demonstrated a decrease in proliferation compared to PSP-treated unfractionated PBL. PMN populations separated from PBL by discontinuous Percoll gradient centrifugation were unresponsive to PSP. Agglutination was observed for the unfractionated PBL and each enriched cell population. These results demonstrate that PSP contains a potent mitogen which induces proliferation in monocyte-enriched cell populations and may reflect the potential of PSP to act as an immune regulator in the uterine environment during early embryo development and implantation. PMID- 8200689 TI - An alteration in the host-parasite relationship in subjects with chronic bronchitis prone to recurrent episodes of acute bronchitis. AB - Acute episodes of bronchitis have been shown to be unequally distributed within a population of subjects with chronic bronchitis. Two groups were identified based on incidence of acute bronchitis--subjects who were 'infection-prone' (2-5 infections per year) and those who were 'non-infection-prone' (0-1 infections per year). Minor differences in clinical parameters existed, except for smoking experience. The non-infection-prone group included more current smokers, and the total smoking experience (in 'pack years') was significantly greater in this group. Between-year analysis demonstrated a stability of classification, established after a minimum of two years' prospective observation. Parameters of the host-parasite relationship were assessed in both groups. A significantly greater polybacterial colonization of the oropharynx was observed for chronic bronchitics, both infection-prone (P < 0.0001) and non-infection-prone (P < 0.001), compared with control subjects. Infection-prone chronic bronchitics had significantly greater total bacteria cultured from the oropharynx compared to the non-infection-prone group (P < 0.05); adherence of indigenous microflora to buccal epithelial cells, in particular Gram-positive cocci (P < 0.01) and in vitro adherence of non-serotypable Haemophilus influenzae to buccal cells (P < 0.05) compared with the control and non-infection-prone groups. These studies suggest that an important variation in subjects with chronic bronchitis is the binding capacity of epithelial cells for bacteria, which when increased enhances susceptibility to colonization and clinical infection. PMID- 8200690 TI - Natural killer and natural cytotoxic cells are present at the maternal-fetal interface during murine pregnancy. AB - NK cell activity has been detected in the early murine decidua, and hypothesized to be mediated by granulated metrial gland (GMG) cells. The possibility that natural cytotoxic (NC) cells are also present in the decidua has not been investigated. In this study mAb to NK cells (anti-NK-1.1) and NC cells (anti-NC 1.1) were used to characterize the decidual cells of days 8-14 pregnant (CBA x C57BL/6) F1 mice. Flow cytometric and immunohistological analyses showed predominantly NK-1.1+ and NC-1.1+ large and granular single nucleated decidual cells with abundant cytoplasm. A 'bright' and a 'dim' subset were identified for both NK-1.1+ and NC-1.1+ cells. The NC-1.1dim and NK-1.1dim cells increased in number and size as pregnancy progressed. When tested in 51Cr-release assays, the decidual cells showed significant levels of both NK and NC activities which increased with progression of pregnancy. The NK and NC activities were partially inhibited (47 and 34%) by preincubation of the decidual cells with anti-NC-1.1 and complement (C'), or anti-NC-1.1 alone. Results indicate that natural cell mediated cytotoxicity in the decidua is in part, at least, mediated by NK-1.1+ and NC-1.1+ cells, and that the NK-1.1dim and NC-1.1dim cells are very likely to be GMG cells. This is the first report of NC cells in the mouse uterus. PMID- 8200691 TI - Phenotype and morphology of murine NC-1.1+ natural cytotoxic cells. AB - The morphology and phenotype of cells identified by the anti-NC-1.1 mAb, 1C4, were studied in CBA and (CBA x C57BL/6) F1 mice. This mAb blocked splenic natural cytotoxic (NC) cell activity in vitro and in vivo. Single colour flow cytometric analysis showed that 6 +/- 1% of all CBA splenocytes were NC-1.1+, and that granular cells of varying sizes, as defined by their forward and side light scatter, contained the highest proportion of NC-1.1+ cells (29 +/- 7%). When analysed by two colour flow cytometry, the large and the granular NC-1.1+ spleen cells in CBA mice were shown to co-express Thy-1.2 and L3T4 (< or = 33%), Mac-1 (< or = 26%), IgM (< or = 60%) and FcR gamma II and J11d (< or = 100%). In contrast, T cell markers were not co-expressed on the small agranular NC-1.1+ spleen cells. This pattern of marker expression was evident in CBA spleens from 2 days of age. When (CBA x C57BL/6) F1 spleen cells were similarly analysed, 82% of granular NC-1.1+ cells also co-expressed NK-1.1. Single colour analysis of CBA bone marrow, thymus, lymph node and peripheral blood leucocytes revealed that < or = 10% of all cells examined were NC-1.1+ while the most granular cells in these organs were 16-43% NC-1.1+. These results support the 'horizontal lineage' theory that NC cells are cells of different lymphohaemopoietic cell lineages at particular stages of differentiation. PMID- 8200693 TI - Transcription of individual genes in eukaryotic cells occurs randomly and infrequently. AB - Experimental evidence is presented indicating that the expression of a lacZ reporter gene driven by the HIV-1 long terminal repeat in a series of stably transfected, cloned macrophage cell lines occurs in a very small proportion of cells. The proportion of cells expressing lacZ, rather than the level of expression in each cell, is regulated by external stimuli such as LPS and phorbol ester. Based upon these and published data we propose that transcription in eukaryotic cells occurs in short pulses interspersed by long periods of inactivity of indeterminate duration. Transcriptional regulation is envisaged as involving changes in the probability rather than the rate of transcription. A probabilistic model of transcription may explain many biological phenomena, such as stem cell division and clonogenic activity, heterogeneous gene expression among clonal cell populations, retroviral latency and cell cycle progression, which appear to involve stochastic decisions. PMID- 8200692 TI - Assays for adjuvanticity of new formulations and of carrier proteins for inducing antibody responses to selected immunogens in the squirrel monkey Saimiri sciureus. AB - Different ways to improve antibody (Ab) responses following immunizations with selected antigens (TT and HSVgD) were investigated, and thus new adjuvant formulations and carrier molecules in a non-human primate experimental host, the squirrel monkey Saimiri sciureus, were assayed. Both quantitative and qualitative humoral responses were determined by means of radio-immunoassays using monoclonal Ab directed at Saimiri IgG. First, the adjuvanticity of the Syntex (SAF-1) adjuvant and of five new adjuvant formulations were assessed towards the selected Ag. This indicated that all the adjuvants induced similar antigen-specific Ab responses, although the adjuvants could modify to some extent the pattern of the qualitative Ab response. Second, we evaluated an adjuvant-free vaccine approach using a synthetic Ag from the circumsporozoite protein of Plasmodium falciparum as immunogen, this Ag being coupled to purified protein derivative (PPD) or to a recombinant heat shock protein from Mycobacterium tuberculosis. These constructs led to good antibody responses as well as an excellent memory effect. Bacille Calmette-Guerin (BCG) priming was required in conjunction with PPD as a carrier molecule to allow homogeneous Ab responses, whereas the heat shock protein construct gave a less homogeneous Ab response regardless of whether a BCG priming was done. We, in addition, discuss the relevance of Saimiri monkeys as experimental models for studies directed at evaluating the immunogenicity of further vaccine candidates. PMID- 8200694 TI - Should we ban B6 supplementation of INH therapy in childhood tuberculosis? PMID- 8200695 TI - Teaching of pediatrics to the medical graduates: a reappraisal. PMID- 8200696 TI - Key issues in medical education: implications of educational technology trends. PMID- 8200697 TI - Inquiry-driven strategies for innovation in medical education: experiences in India. AB - Four medical institutes, viz, AIIMS, New Delhi; CMC, Vellore; JIPMER, Pondicherry and IMS-BHU, Varanasi formed a consortium to introduce reforms in undergraduate medical education. A detailed inquiry was conducted by administering questionnaires to the faculty, recent graduates and patients to identify the deficiencies in the present system. Morbidity patterns prevalent in the community at primary, secondary and tertiary care levels were determined. These were matched with the actual curricula being followed and the assessment patterns. The main findings were: inadequate emphasis on practical skills (including communication), insufficient coverage of common diseases; and neglect of behavioral, social and ethical aspects in the curriculum. Based on these findings certain corrective programmes are being introduced. The content areas in the curriculum have been classified in to 'must know', 'good to know' and 'need not know'. A list of essential skills have been identified. Steps are on to ensure that these skills are acquired by the graduates. A modular approach to the teaching was suggested and modules on some of these topics are under preparation. PMID- 8200698 TI - Need-based undergraduate medical curriculum. AB - There is a growing concern over the quality of medical education for undergraduates in India. This paper is an attempt to define a need-based curriculum and outline the initiatives taken by the Medical Council of India (M.C.I.) in developing a need-based curriculum. The steps include: clear delineation of goals and objectives of education; adoption of innovative teaching and learning methodology, adjustments in the course structure, updating of course content, rationalizing assessment strategy, and emphasis on structured and skill oriented internship. For effective implementation of these measures, strategies such as establishment of Medical Education Unites (MEUs), visible funding of education, more recognition to teaching and impetus to staff development activities have been suggested. PMID- 8200699 TI - Innovative programmes of medical education: I. Case studies. AB - This paper discusses five innovative programmes in medical education with the view of giving a glimpse of the new approaches to the education of physicians. Each one of them has unique features and provides useful lessons. The School of Medicine, McMaster University, Hamilton (Canada), pioneered the use of interdisciplinary problem based learning. The programme obliterates the basic science and clinical science dichotomy, and involves self-directed, small group (tutorial) learning as the principal educational method. Faculty of Medicine, University of Sherbrooke (Canada) shows the way for introduction of innovative problem-based curriculum in a traditional medical school. The University Centre for Health Sciences, Ben Gurion University of the Negev, Beersheva (Israel), serves as the nodal point of the health care system in the region. Merging of the service and the educational systems has not only succeeded in better community orientation of graduates, but also in improving the health care availability in the region. The University of Philippines, College of Medicine, Institute of Health Sciences, Tacloban (Philippines), trains grassroot workers as well as physicians. Through a ladder-type curriculum, a health worker can rise to become a doctor of medicine. The Chulalongkorn University Medical School, Bangkok, Thailand, has successfully run a parallel innovative track for students of rural background. The students are identified from the underserved areas, and are given a large part of their clinical training at the provincial/district hospitals. The programme has succeeded in inculcating favourable attitudes towards working in rural areas, and in improving the care at provincial/district hospitals. These innovative programmes have emerged as role-models for bold experimentation in medical education. PMID- 8200700 TI - Innovative programmes of medical education: II. Commentary and lessons for India. AB - Major areas in which innovative approaches in medical education have been tried include student selection, learning strategies, and community orientation. It is relatively easier to implement innovations in a new institution. In established medical schools, running two simultaneous curricula tracks, the traditional and the innovative has emerged as a popular strategy for introducing new systems of education. Institutional commitment to the objectives and matching implementation effort determine the success of an innovative programme. Stronger links between the medical education and health service systems not only enhance the community orientation of the graduates, but also help improve the quality of health care provided to the community. There is a need to experiment with innovative approaches to education of physicians in our country. Establishment of medical education units in medical schools will be a practical beginning in the right direction. PMID- 8200701 TI - Clinical course of isolated ventricular septal defect: an Indian experience. AB - To define the clinical course of ventricular septal defect, 410 consecutive patients with isolated ventricular septal defect were evaluated over a period of 13 years. Their age ranged from 12 days to 24 years at the time of first visit to the hospital. Patients with less than 2 years follow-up period were excluded. One hundred and fifty seven patients were one year of age or less. The left to right shunt size remained the same in 52.4% of cases. In 34.4% the shunt size decreased, with complete closure of ventricular septal defect in 8.8%. Closure of ventricular septal defect was observed even in patients who had initially presented with large left to right flow, and congestive heart failure in infancy. Right ventricular outflow tract obstruction developed in 8.5% of patients usually between 2 and 10 years of age. Murmur of aortic regurgitation appeared in 8.9% on follow-up. Infective endocarditis developed in 6 cases. The unfortunate complication of Eisemenger's complex was seen in 3 patients; they had not returned for follow up for a long period of time. Hence, our data show that the left to right shunt across the ventricular septal defect decreases in about one third of patients. However, a regular follow up is essential to prevent development of Eisenmenger's complex and for early detection of other complications like aortic regurgitation and right ventricular outflow tract obstruction. PMID- 8200702 TI - Epidemiological characteristics of new borns in a rural community. AB - All births (1211) were recorded in a rural area for 1985 by monthly domiciliary visits and the sociological characteristics were collected from mothers within a month. The analysis of 1201 births is presented: 52.7% were male births, 95.7% were delivered in village itself, 80.4% were delivered by trained dais, 99.5% were live born, 12.9% were born before 37 weeks of gestation, 61.5% were put to breast feed within 6 hours, 35% were of gravida 4 and above, 68.9% did not receive any antenatal care, 67.1% had not received any tetanus toxoid, 70.8% did not receive any folifer tablet, 0.8% had abortion and another 0.8% had still birth in preceding outcome, 1.58% had lost a live born dead in preceding out come, 89.6% stopped breast feeding at conception, 31.7% had birth interval less than 2 years, but 2.2% had less than one year, 2/3rd were born in second half of the year, 17.8% had taken extra food during pregnancy, 21.2% reduced the work after becoming pregnant, 9.5% were born to mothers of less than 20 years age, 98.5% of mothers were housewives and 95.9% mothers were illiterate, 33.5% were born in nuclear family, 22.3% were living in 'Kacha' house, 34.8% had no electricity connection, 37.0% were born to land less, 42.2% had no radio in the house, 7.1% had no conveyance, 52.0% families had piped water supply. These findings have been discussed here. PMID- 8200704 TI - Neonatal candidemia. AB - Fifty five clinically diagnosed cases of neonatal septicaemia of the nursery ward, Medical College Hospital Calcutta were subjected to blood culture on two consecutive days in all cases. Bacterial isolates were found in 34 (61.8%) cases as pure growth and candida species from 9 (16.4%) as pure culture. Remaining 12 samples did not yield any growth. Species distribution of candida showed C. albicans 6, C. parapsilosis 2, and C. guillermondii 1. Asphyxia neonatorum was the common feature in all cases of candidaemia. All neonates with candidal infection were low-birth-weight and premature. C. albicans, the predominant species (66.6%) recovered, was responsible for a localised outbreak of infection in the nursery. PMID- 8200703 TI - Bronchial asthma and wheeze in a desert country. AB - A cross-sectional, population-based study was conducted among school children (3300), aged 7-12 years, in the Kingdom of Saudi Arabia, during the period January, 1988-February, 1990. The aim of the study was to investigate the association between asthma, allergic rhinitis, wheeze and eczema among Saudi school children. The relationship between pet-ownership and respiratory allergy was also studied. Detailed information was collected about wheeze and asthma in 3041 children and history of asthma and allergic rhinitis in their parents. The population sample had a high prevalence rate of diagnosed asthma (6.8%), history of wheeze (10.5%), allergic rhinitis (17.9%), and eczema (10.8%). Allergic rhinitis was the most frequently seen respiratory illness when compared to other respiratory symptoms. The prevalence rate of asthma, allergic rhinitis and eczema among parents reflected the same pattern as that seen in the children. Prevalence rate for asthma in children with pets is twice that of children without pets (OR: 2.4; 95%, Cl: 1.8-3.1). The odds of having chronic cough (OR: 3.9; 95% Cl: 2.8 5.2), chronic wheeze (OR: 4.2; 95%, 3.3-5.4), allergic rhinitis (OR: 8.0; 95% Cl: 6.3-10.3) and eczema (OR: 2.8: 95 Cl: 2.1-3.7) was higher in children with pets than in children without pets. The present study revealed that pet-ownership was associated with increased respiratory symptoms. PMID- 8200706 TI - Ultrasonographic fetal nomograms of anterior ventricular hemisphere ratio (AVHR) and posterior ventricular hemisphere ratio (PVHR) for early prenatal diagnosis of hydrocephalus. AB - Serial ultrasound scans were done in 150 fetuses between 14th to 22nd week of gestation to establish the nomograms of anterior ventricular hemisphere ratio (AVHR) and posterior ventricular hemisphere ratio (PVHR). Of 150 fetuses, 100 were in the high risk group for neural tube defect and 50 were in the control group. The study indicates that the value of AVHR decreases from 0.62 to 0.50 and PVHR from 0.60 to 0.50 between 14th to 22nd week of gestation. No statistical difference was observed in the values of AVHR and PVHR in high risk and low risk (control) cases (p > .001). The value of AVHR or PVHR greater than 0.5 after 18 weeks of gestation or more was considered pathological for hydrocephalus. In 2, out of 3 cases of hydrocephalus detected in our series, the value of AVHR and PVHR was 0.7 at 20 weeks and in the third case it was 0.6 at 18 weeks. All of these values were 3 SD above the normal for the period of gestation. PMID- 8200705 TI - Arthritis in children: an occult manifestation of Bancroftian filariasis. AB - A form of unexplained arthritis, not attributable to known causes, seen in children (0-14 yrs) in this endemic zone of Bancroftian filariasis was investigated for its association with filariasis. Nineteen cases of undiagnosed arthritis were screened for filarial IgG antibodies to Wuchereria by Stick Enzyme Linked Immunosorbent Assay (ELISA). All had large joint involvement, the commonest joint affected being the knee joint. Involvement was monoarticular in 10 and binarticular in 9. Joint pain was present in 18 and effusion in 12. Five patients had recurrent episodes. Sixteen (84.2%) showed filarial antibodies of which only one (5.3%) was microfilaraemic. Patients with classical filariasis (16), disease controls (10), endemic normals (15) and non-endemic normals (10) were also subjected to ELISA to ascertain the sensitivity and specificity of the technique. Fifteen (93.8%) cases of classical filariasis and 1 (6.7%) of endemic normal were antibody positive, whereas none of disease controls and non-endemic normals had filarial antibodies. Nine cases of filarial arthritis reviewed after a course of Diethylcarbamazine showed satisfactory response to treatment. PMID- 8200707 TI - Spondylocostal dysostosis. AB - Spondylocostal dysostosis is a rare condition characterized by short stature due to a short trunk, multiple morphological abnormalities of the vertebrae and ribs due to malsegmentation of the axial skeleton. Radiological features include reduced number of vertebrae and ribs, hemivertebrae, fused or sagitally cleft vertebrae or multiple rib fusions. Three distinct clinical entities are described. We report nine cases of this syndrome, seven were infants and presented with an abnormal shape of the thorax. Two of them had a meningocoele, and one succumbed to the CNS anomalies on the third day of life. The other two cases were two and eight years of age. Cardiac lesion was detected in one case and renal malformations in three cases. Reduction in the rib number was present in all cases, and rib fusion in seven cases. Thoracic vertebral dysegmentation was noted in all, lumbar in three and cervical in one case. This is the first large series from India. No clear single etiology was established. PMID- 8200708 TI - Kala-azar in Trabzon (eastern Black Sea) region of Turkey. PMID- 8200709 TI - Spontaneous gastric perforation in neonates. PMID- 8200710 TI - Early onset juvenile diabetes mellitus controlled with nicotinic acid therapy. PMID- 8200711 TI - Pulmonary alveolar proteinosis. PMID- 8200712 TI - Transillumination--a lost clinical skill. PMID- 8200713 TI - Intramural duodenal hematoma following blunt bicycle handle bar injury. PMID- 8200714 TI - Pseudomemory in hypnotized and simulating subjects. AB - High hypnotizable (n = 23) and low hypnotizable simulating (n = 13) subjects received pseudomemory suggestions. High hypnotizable and low hypnotizable simulating subjects were equally likely to pass the target noise suggestion during hypnosis and were also equally likely (high hypnotizables, 47.83%; low hypnotizable simulators, 64.29%) to report pseudomemories when tested for pseudomemory after instructions to awaken. As in previous research with task motivated subjects, pseudomemory rate (high hypnotizables, 47.48%; low hypnotizable simulators, 46.15%) was not reduced by informing subjects that they could distinguish fantasy and reality in a nonhypnotic state of deep concentration. At final inquiry, after deep concentration, high hypnotizable and low hypnotizable simulating subjects' pseudomemories remained comparable (43.48% and 38.46%, respectively). Unlike previous research, high hypnotizable subjects did not report more unsuggested noises and more pseudomemories of novel sounds than did awake low hypnotizable simulating subjects. Pseudomemory reports were generally consistent with subjects' ratings of whether the hypnotist expected them to believe the sounds were real or imagined. PMID- 8200715 TI - Parallel application of the experiential analysis technique with subject and hypnotist: a new possibility for measuring interactional synchrony. AB - The Parallel Experiential Analysis Technique (PEAT), a new method for gathering data on the subjective experiences of both the hypnotist and the subject, is described. The PEAT is an interactional modification of the Experiential Analysis Technique (EAT). Procedural details and methodological observations resulting from the modification of the EAT are discussed. Suggestions on how to characterize the phenomenology of the hypnotic interaction and to determine the degree of interactional synchrony on the subjective level between the hypnotist and subject are made. PMID- 8200716 TI - Autonomic changes during hypnosis: a heart rate variability power spectrum analysis as a marker of sympatho-vagal balance. AB - Spectral analysis of beat-to-beat variability in electrocardiography is a simple, noninvasive method to analyze sympatho-vagal interaction. The electrocardiogram is analyzed by means of an automatic, autoregressive modeling algorithm that provides a quantitative estimate of R-R interval variability by the computation of power spectral density. Two major peaks are recognizable in this specter: a low-frequency peak (LF, -0.1 Hz), related to the overall autonomic activity (ortho+parasympathetic) and a high-frequency peak (HF, -0.25 Hz), representative of the vagal activity. The LF/HF ratio is an index of the sympatho-vagal interaction. This technique was applied, using a computer-assisted electrocardiograph, to 10 healthy volunteers (6 high and 4 low hypnotizable subjects as determined by the Stanford Hypnotic Susceptibility Scale, Form C) in randomized awake and neutral hypnosis conditions. Preliminary results indicated that hypnosis affects heart rate variability, shifting the balance of the sympatho-vagal interaction toward an enhanced parasympathetic activity, concomitant with a reduction of the sympathetic tone. A positive correlation between hypnotic susceptibility and autonomic responsiveness during hypnosis was also found, with high hypnotizable subjects showing a trend toward a greater increase of vagal efferent activity than did low hypnotizables. PMID- 8200717 TI - Why dissociative disordered patients are fundamentally responsible: a master class commentary. PMID- 8200718 TI - "Cyberphysiologic" strategies for children: the clinical hypnosis/biofeedback interface. AB - This article presents an in-depth discussion of the integrated use of self hypnosis and biofeedback in the treatment of pediatric biobehavioral disorders. The rationale for integrating these techniques and their similarities and differences are discussed. The concepts of children's imaginative abilities, mastery, and self-regulation are examined as they pertain to these therapeutic strategies. Three case studies are presented that illustrate the integrated use of self-hypnosis and biofeedback in the treatment of children with psychophysiologic disorders. The authors speculate on the specific aspects of these self-regulation or "cyberphysiologic" techniques that appear particularly relevant to positive therapeutic outcomes. PMID- 8200719 TI - Correlation of serum ofloxacin concentration and serum creatinine level in patients on prolonged therapy. AB - Serum ofloxacin concentrations were assessed by high performance liquid chromatography 4 h after drug administration in 86 patients with pulmonary tuberculosis. All patients had multidose, once-daily drug administration (200 mg to 800 mg p.o.) for at least 3 weeks prior to assessment. The serum creatinine levels were simultaneously assessed for these patients. A positive correlation was found between serum ofloxacin (Y) and serum creatinine x dose of ofloxacin administered/body surface area (X). The correlation can be represented mathematically by the equation: Y = 0.87X + 0.68 (r = 0.80, p < 0.001). PMID- 8200720 TI - Inhibition of leukotriene release by mofebutazone: a possible clinical advantage. AB - The isolated perfused lung preparation from actively sensitized guinea-pigs was used; after it was challenged with antigen, mediators such as histamine, prostaglandins and leukotrienes were released into the lung effluent. It was found that treatment of the perfused lungs before and during challenge with mofebutazone (10 micrograms/ml) inhibited the immunological release of prostaglandins as well as leukotrienes. Phenylbutazone, on the other hand, at the same dose level inhibited the release of prostaglandins, whereas the release of leukotrienes was much less affected by the drug. Histamine release was not altered by either drug. When clinically mofebutazone tablets (300 mg) were given as an analgesic twice daily for 15 days to a number of asthmatic volunteers including 3 aspirin-sensitive individuals, there was no increase in the incidence or intensity of the asthmatic attacks, even in the aspirin-sensitive patients. Pulmonary ventilatory functions which showed a certain obstructive pattern were not worsened by the treatment and even tended to be somewhat improved. PMID- 8200721 TI - Action of 2-acetoxy-trifluoromethylbenzoic acid (Triflusal) on platelet function after repeated oral administration in man: a pharmacological clinical study. AB - The efficacy and safety of Triflusal capsules given to patients at thrombogenetic risk because of platelet hyperaggregation were investigated in a controlled study involving 15 patients (9 males and 6 females, mean age 65.7 years) who were given 300 mg/day of Triflusal during the first 5 days and 600 mg/day during the following 5 days. Subsequently, after 7 days of wash-out all these patients received placebo for 10 days, one capsule for the first 5 days and 2 capsules for the following 5 days. The platelet antiaggregant activity of the drug was evaluated by means of Born's platelet activation test. Specific tests were also made to assess the effect of this substance on platelet release and the coagulation system. The safety was evaluated by measuring the most important clinical chemistry and clinical haematology indexes of haematopoietic, hepatic, renal and metabolic functions. Arterial blood pressure and heart rate values were also recorded. All the 15 patients completed the study. It was found that the Triflusal treatment led to a significant mean reduction of the indexes chosen as markers of thrombophilia or platelet hyperaggregation in vivo. It did not affect the normal haemostatic-coagulation process and was well tolerated by the patients. The subsequent placebo treatment did not induce any platelet antiaggregant effects. PMID- 8200722 TI - Effects of seaprose on sputum biochemical components in chronic bronchitic patients: a double-blind study vs placebo. AB - Seaprose is a semialkaline proteinase endowed with proteolytic effect and antiinflammatory activity tested in different clinical trials. There is clinical evidence that seaprose reduces sputum viscoelastic properties in chronic hypersecretory bronchitis. The present study evaluated (in a double-blind design vs. placebo) the activity of seaprose on bronchial inflammation, mucus glycoprotein secretion and bronchial humoral defence mechanism in chronic bronchitic patients clinically stable (10 per group). Markers of bronchial inflammation (albumin, albumin/total protein ratio) and bronchial infection (DNA), of mucus glycoproteins (fucose and N-acetylneuraminic acid) and of humoral defence mechanism (secretory-IgA) were tested in sputum. We found that ten-day treatment with seaprose (90 mg/day) reduced sputum albumin during the observation period, the difference being statistically significant at the 18th day. The sputum albumin/total protein ratio also decreased by 50% at the end of the study. In the same group, sputum DNA, secretory-IgA, fucose and N-acetylneuraminic acid remained unchanged after treatment. The placebo group did not show any significant changes in the sputum marker substances. This study provides experimental evidence for the antiinflammatory activity of seaprose on bronchial mucosa in chronic bronchitic patients studied in a stable phase of their disease. Furthermore the drug does not seem to affect mucus glycoprotein secretion or secretory-IgA production. PMID- 8200723 TI - Pharmacokinetics and electroencephalographic effects of darodipine 50-200 mg modified release (MR) acute oral administration: dose-finding study in healthy volunteers. AB - Pharmacokinetics and electroencephalographic [EEG; power spectral analysis] effects of the acute oral Ca-antagonist darodipine (50 mg MR, 100 mg MR, and 200 mg MR) were investigated in a cross-over, placebo-controlled study on healthy male volunteers (age 23-28 yrs). No effects on heart rate, blood pressure or behaviour were observed with these doses at average Cmax levels ranging between 4.74 and 33.53 ng/ml and with a Tmax ranging from 2 to 6 h depending on the dose. No significant differences in drug kinetics were observed between the 100-mg and the 200-mg dose. A significant increase of EEG total power and a decrease of relative power in the 14.5-32.0 Hz frequency interval were observed at the 100-mg and 200-mg doses. These effects were greater and more consistent across subjects at 100 mg than at 200 mg, and were correlated with darodipine plasma concentrations, with indications of an active concentration threshold at approximately 4-5 ng/ml. The 50-mg dose proved ineffective on the EEG signal. PMID- 8200724 TI - The evolving duty of mental health professionals to third parties: a doctrinal and institutional examination. PMID- 8200725 TI - Does multiple personality disorder exist? The beliefs, the data, and the law. PMID- 8200726 TI - Revisiting the parable: truth without consequences. PMID- 8200727 TI - The right to refuse mental health treatment: a therapeutic jurisprudence analysis. PMID- 8200728 TI - Synthesis of the partially protected fragment 1-16 of salmon calcitonin by using the phenylhydrazide protecting group. AB - The partially protected fragment BOC-Cys(Acm)-Ser(But)-Asn-Leu-Ser(But)-Thr(But)- Cys(Acm)-Val-Leu-Gly-Lys(epsilon-BOC)-Leu-Ser(But)-Glu(OBut)-Leu-O H of salmon calcitonin was synthesized by segment condensation in solution. Segments were synthesized in solution by the DCC/HOBt method using the phenylhydrazide as a semipermanent protecting group for protection of the carboxyl function of the C terminal residue. The phenylhydrazide protecting group was removed by oxidation with air oxygen catalyzed by copper-pyridine complexes. The segments were then condensed by the DCC/HOBt method according to the scheme (6 + 3) + (3 + 4). The proposed synthetic scheme permits production of gram amounts of the partially protected fragment 1-16 of salmon calcitonin. PMID- 8200729 TI - Solid-phase synthesis of (tyrosyl-alanyl-glutamyl)n by segment condensation. AB - (Tyr-Ala-Glu)n, n = 1-9, were synthesized by segment condensation using the Fmoc/tert-butyl protection strategy and solid-phase techniques. The C-terminal residue was coupled to the resin and the peptides were built out by adding Fmoc Glu(O-t-Bu)-Tyr(t-Bu)-Ala-OH units. When the desired lengths were reached the peptides were capped with Fmoc-Tyr(t-Bu)-Ala-OH units. Fmoc-Tyr(t-Bu)-Ala-OH and Fmoc-Glu(O-t-Bu)-Tyr(t-Bu)-Ala-OH were synthesized in aqueous solution by the successive addition of N-hydroxysuccinimide esters of Fmoc-Tyr(t-Bu) and Fmoc Glu(O-t-Bu) to the growing chain. Neither sequential amino acid addition or segment condensation techniques were successful on polystyrene supports. However, the segment condensations were highly successful on kieselguhr-supported polydimethylacrylamide based resins. (Tyr-Ala-Glu)n, n = 1-9, were tested as inhibitors of the protein tyrosine kinase, pp60c-src. Inhibition, as measured by IC50 values, increased with increasing size of the peptide. PMID- 8200730 TI - Pegylated peptides. II. Solid-phase synthesis of amino-, carboxy- and side-chain pegylated peptides. AB - General procedures are presented for the site-specific pegylation of peptides at the NH2-terminus, side-chain positions (Lys or Asp/Glu) or COOH-terminus using solid-phase Fmoc/tBu methodologies. A model tridecapeptide fragment of interleukin-2, IL-2(44-56)-NH2, was chosen for this study since it possesses several trifunctional amino acids which serve as potential sites for pegylation. The pegylation reagents were designed to contain either Nle or Orn, which served as diagnostic amino acids for confirming the presence of 1 PEG unit per mole of peptide. NH2-Terminal pegylation was carried out by coupling PEG-CH2CO-Nle-OH to the free NH2-terminus of the peptide-resin. Side-chain pegylation of Lys or Asp was achieved by one of two pathways. Direct side-chain pegylation was accomplished by coupling with Fmoc-Lys(PEG-CH2CO-Nle)-OH or Fmoc-Asp(Nle-NH CH2CH2-PEG)-OH, followed by solid-phase assemblage of the pegylated peptide-resin and TFA cleavage. Alternatively, allylic protective groups were introduced via Fmoc-Lys(Alloc)-OH or Fmoc-Asp(O-Allyl)-OH, and selectively removed by palladium catalyzed deprotection after assemblage of the peptide-resin. Solid-phase pegylation of the side-chain of Lys or Asp was then carried out in the final stage with PEG-CH2CO-Nle-OH or H-Nle-NH-(CH2)2-PEG, respectively. COOH-Terminal pegylation was achieved through the initial attachment of Fmoc-Orn(PEG-CH2CO)-OH to the solid support, followed by solid-phase peptide synthesis using the Fmoc/tBu strategy. The pegylated peptides were purified by dialysis and preparative HPLC and were fully characterized by analytical HPLC, amino acid analysis, 1H-NMR spectroscopy and laser desorption mass spectrometry. PMID- 8200731 TI - X-ray studies on crystalline complexes involving amino acids and peptides. XXVI. Crystal structures of two forms of L-histidine acetate and a comparative study of the amino acid complexes of acetic acid. AB - L-Histidine acetate crystallizes in two forms: (I) orthorhombic; P2(1)2(1)2(1); a = 5.027, b = 11.126, c = 17.473 A; Z = 4; (II) monoclinic; C2; a = 15.649, b = 9.276, c = 8.566 A; beta = 94.65 degrees; Z = 4. The structures were solved by direct methods and refined to R-values of 0.056 and 0.089 for 1131 and 1330 observed reflections, respectively. The conformations of the histidine molecule in the two forms are different. However, both are such that they facilitate the occurrence of a specific interaction of the histidine molecule with a carboxylate group. The basic elements of aggregation are hydrogen-bonded histidine ribbons, but they are of different types in the two structures. The ribbons are interconnected by acetate ions to form the crystals. The structures contain two characteristic interaction patterns involving amino and carboxylate groups, one of which is observed for the first time. The two water molecules in form II and their symmetry equivalents form an uninterrupted hydrogen-bonded chain running through the crystal. They also present an interesting case of disorder in hydrogen bonds. A comparative study involving amino acid complexes of acetic acid shows that the presence of acetate ion could lead to new aggregation patterns, specific interactions and characteristic interaction patterns with varying degrees of similarity with those observed in other structures containing amino acids. PMID- 8200732 TI - Chemical synthesis of O-thiophosphotyrosyl peptides. AB - The synthon for O-thiophosphotyrosine, Fmoc-Tyr[PS(OBzl)2]-OH (1c), was prepared in 63% yield from Fmoc-Tyr-OH by first transient protection as the tBuMe2Si-ester and phosphinylation with (BzlO)2PNiPr2/tetrazole followed by oxidation of P(III) to P(V) with S8 in CS2. Building block 1c was incorporated in the Fmoc solid phase synthesis of two O-thiophosphotyrosine-containing peptides H-Thr-Glu-Pro Gln-Tyr(PS)-Gln-Pro-Gly-Glu-OH (2) and H-Thr-Arg-Asp-Ile-Tyr(PS)-Glu-Thr-Asp-Phe Phe-Arg-Lys-OH (3), corresponding to sequences of the p60src (523-531) protein and an insulin receptor (IR) (1142-1153) analogue, respectively. An alternative approach of synthesis, the global phosphorylation of a resin-bound peptide, also proved useful. Thus, the free tyrosyl side-chain containing-peptide IR (1142 1153) on support was phosphinylated with the above phosphoramidite reagent followed by oxidation with either S8/CS2 or tetraethylthiuram disulfide/CH3CN solutions. Deprotection and peptide-resin cleavage was performed with a TFA/thiophenol (H2O) mixture. Crude peptides 2 and 3 were stable to the acidolytic deprotection. Preparative RP(C18)HPLC was initially performed using 0.1% TFA(aq)/EtOH solvents. However, analyses of fractions resulting from the purification step indicated significant decomposition of thiophosphopeptide in solution. Stability measurements both as a function of time and pH, further confirmed this initial finding. Purifications performed at intermediate pH using a triethylammonium acetate (pH 7.5)/CH3CN solvent system overcame this problem. PMID- 8200733 TI - Local structural differences between alpha- and beta-elicitins shown by circular dichroism and ultraviolet difference spectroscopy. AB - In order to investigate differences in the conformation of elicitins exhibiting different levels of activity (toxicity to tobacco plants), the environment of the tyrosyl residues in four elicitins has been compared by different spectroscopic methods (difference absorption and circular dichroism). We compared two alpha elicitins (capsicein and parasiticein) and two beta-elicitins (beta-cryptogein and beta-cinnamomin), that are 50-100 times more toxic than the alpha-ones. Thermal difference UV spectroscopy and titration experiments clearly showed the exposure of Tyr-85 by comparison of parasiticein lacking Tyr-85 and the accessibility of its hydroxyl group to the solvent. The adjacent Tyr-87 was also suggested to be located at the surface. In beta-cryptogein, beta-cinnamomin and capsicein the pK was measured at between 10.5 and 10.8, while in parasiticein it is higher (11.5) owing to a difference in the local environment. Thermal difference UV spectroscopy showed one more exposed tyrosine in beta-elicitins than in alpha-ones. This difference was attributed to Tyr-12, considering the more hydrophilic characteristic of the sequence around residue 13 in beta elicitins and the role of this region in the toxicity. However, no difference in titration behaviour was noted among elicitins concerning Tyr-12. The other two tyrosines also presented an abnormal pK of titration (> 12). In all elicitins Tyr 47 was probably exposed, while Tyr-33 was probably buried and not titrated, except in beta-cinnamomin at very alkaline pH. PMID- 8200734 TI - Conformation of the oxalamide group in retro-bispeptides. Three crystal structures. AB - We have determined the structures of a range of peptides having the oxalamide ( NH-CO-CO-NH-) unit located at their center. The oxalamide group has the trans conformation in two retropeptides and an approximately orthogonal conformation in the peptide with Pro residues. Torsional angles about the CO-CO bond are 180 degrees in MeO-Aib-CO-CO-Aib-OMe (1), 175 degrees in MeO-L-Leu-CO-CO-L-Leu-OMe (2), and -108 and -106 degrees for the two independent molecules in the crystal of MeO-L-Pro-CO-CO-L-Pro-OMe (3), owing to steric hindrance between CO and the pyrolidine ring. Crystal data are: (1) C12H20N2O6, triclinic, space group P1, a = 6.190(1), b = 10.044(2), c = 11.989(2) A, alpha = 86.13(12), beta = 83.13(2), gamma = 80.16(2) degrees, R = 0.057 for 1646 observed reflections [magnitude of Fo > 3 sigma (magnitude of Fo)]; (2) C16H28N2O6, tetragonal, space group P4(1), a = b = 11.121(3), c = 15.775(6) A, R = 0.058 for 1216 observed reflections [magnitude of Fo > 3 sigma (magnitude of Fo)]; (3) C14H20N2O6, monoclinic space group P2(1), a = 9.556(2), b = 17.864(3), c = 9.618(2) A, beta = 104.35(1) degree; R = 0.051 for 2100 observed reflections [magnitude of Fo > 3 sigma (magnitude of Fo)]. PMID- 8200735 TI - Simultaneous multiple synthesis and selective conjugation of cyclized peptides derived from a surface loop of a meningococcal class 1 outer membrane protein. AB - Starting from the alpha-(2,4-dimethoxybenzyl) ester of N-(9 fluorenylmethoxycarbonyl)aspartic acid [Fmoc-Asp-ODmb], side-chain-protected resin-bound Fmoc-peptides containing an N epsilon-1-(4,4-dimethyl-2,6 dioxocyclohexylidene)ethyl lysyl [Lys(Dde)] residue were prepared. The C-terminal dimethoxybenzyl esters of aspartic acid were removed with 1% trifluoroacetic acid and 10% anisole in dichloromethane, followed by Fmoc-cleavage in the usual manner. The resin-bound peptides were then cyclized using 1-benzotriazolyloxy tris-[N-pyrrolidino]phosphonium hexafluorophosphate (PyBOP) in the presence of N methylmorpholine. The (dimethyldioxocyclohexylidene)ethyl groups of lysine were removed with 1% hydrazine hydrate in N,N-dimethylacetamide, and the liberated side-chain amino functions were modified by reaction with pentafluorophenyl S acetylmercaptoacetate (SAMA-OPfp). Finally, the peptides were side-chain deprotected, with exception of the Lys(SAMA) residue, and cleaved from the solid support with trifluoroacetic acid/anisole/water, 95/2.5/2.5. Cyclic peptides comprising 7-14 amino acid residues were obtained employing this procedure. As a model conjugation, cyclo[Thr-Asn-Asn-Asn-Leu-Lys(SAMA)-Thr-Lys-Asp] was coupled with bromoacetamide. The same peptide was also coupled with a bromoacetylpeptide to give a well defined peptide/peptide conjugate. All peptides were conjugated to bromoacetylated tetanus toxoid for immunization purposes. PMID- 8200736 TI - Synthesis and surface activity properties of hydrophobic/hydrophilic peptides. AB - In order to explore the ability of amphiphilic peptides to behave as surface active agents with emulsifying properties, several short peptides of leucine and glutamine were synthesized with different periodicity, length and hydrophobic characteristics. The stepwise liquid-phase procedure using the N hydroxysuccinimide ester was deployed in all chain-lengthening steps, and the same procedure was also used subsequently to modify some of the products by introducing a lipophilic moiety such as a palmitoyl residue. The surface-active properties of these products were evaluated by measuring the variation of surface (gamma s) and interfacial (gamma i) tensions and the formation of micelles as a function of concentration in aqueous solution. The alternating sequence (Leu Gln)n showed good surface activity behaviour, similar to those of recognized surfactants, albeit with no emulsifying function. More hydrophobic compounds, such as lipopeptides, lowered the surface tension of water at concentrations markedly below those usually observed for classical surfactants, and emulsifying properties were observed in all the peptides substituted with lipophilic moieties. PMID- 8200737 TI - Comments on the use of a dichromophoric circular dichroism assay for the identification of beta-turns in peptides. AB - Use of the dichromophoric CD assay for beta-turn formation in peptide sequences has been investigated. The assay involves the observation of Cotton effects in CD spectra, originating from the approach of N- and C-terminal aromatic chromophores in tetrapeptides. The approach of the chromophores was believed to be brought about by a beta-turn in the peptide structure. Our investigations were paralleled by NMR studies which revealed the presence of a previously unreported hydrogen bond in the beta-turn conformers, which appears to play a role in the generation of the observed Cotton effects. This suggests caution in the use of the CD technique alone as an assay for beta-turn conformers in peptides. PMID- 8200738 TI - Reinvestigation of the reactions of carbodiimides with alkoxycarbonylamino acid symmetrical anhydrides. Isolation of two N-acylureas. AB - Alkoxycarbonylamino acid symmetrical anhydrides were allowed to react with N,N' diisopropylcarbodiimide. The determination of the decrease in carbodiimide concentration indicated that the reaction was slow and proceeded indirectly. It is presumed that symmetrical anhydride in the presence of basic carbodiimide is converted into oxazolone and alkoxycarbonylamino acid. The latter reacts with carbodiimide to give O-acylisourea which, in turn, rearranges to N-acylurea. A second minor product was found to be N-(N1,N2-bisalkoxycarbonyldipeptidyl)urea. The main pathway leading to the formation of this product starts with rearrangement of the symmetrical anhydride to N1,N2-bisalkoxycarbonyldipeptide acid. These experiments suggest that the reaction between anhydride and carbodiimide is not the source of N-acylurea in peptide synthesis. PMID- 8200741 TI - Different sequence environments of amino acid residues involved and not involved in long-range interactions in proteins. AB - No method has yet been available to decode information, hidden in the protein primary structure, on long-range interactions of amino acids. Even a limited amount of information on long-range interactions could help in conformational energy calculations of protein structures and could lead to a better understanding of how the primary structure of proteins determines their conformation. The sequence environments of amino-acid residues were compared from the viewpoint of their participation in long-range interactions. By using the simplest definition, residues were considered as partners in a long-range interaction if they were at least 20 residues apart in the sequence and their C alpha distance was less than 7 A. In spite of this rather crude definition, an analysis of 88 unrelated proteins has shown that the sequence environments (10 residues on each side) of those amino acids which are involved in long-range interactions and of those which are not are significantly different according to the criteria of mathematical statistics. Moreover, in many cases the differences are so pronounced that the involvement of a given amino acid in long-range interactions can be predicted from its sequence environment. PMID- 8200739 TI - Solid-phase synthesis of cionin, a protochordate-derived octapeptide related to the gastrin/cholecystokinin family of peptides, and its mono-tyrosine-sulfate containing derivatives. AB - Cionin, a protochordate-derived octapeptide amide related to the gastrin/cholecystokinin family of peptides, contains two consecutive tyrosine sulfate residues. In order to gain insight into the role of the respective tyrosine sulfate residue in biological activity, cionin and its derivatives in which one of the two tyrosine sulfate residues was replaced by tyrosine, were prepared by two Fmoc-based solid-phase approaches. In approach (1) Fmoc Tyr(SO3Na)-OH was employed as a building block to assemble the Tyr(SO3Na) containing peptide-resin, and a global deprotection/cleavage was conducted with 90% aqueous TFA in the presence of m-cresol and 2-methylindole at 4 degrees C. In approach (2) the Tyr(Msib) [Msib = p-(methylsulfinyl)benzyl] derivative was used for the peptide-chain assembly to achieve sulfation on the selective Tyr residue. Partially protected peptide with the Msib/Msz protecting groups [Msz = p (methylsulfinyl)benzyloxycarbonyl], obtained after peptide-resin cleavage, was treated with DMF-SO3 complex in the presence of ethanedithiol to achieve the sulfation of free Tyr residue and the reduction of the Msib/Msz groups to TFA labile Mtb/Mtz groups [Mtb = p-(methylthio)benzyl, Mtz = p (methylthio)benzyloxycarbonyl]. Final deprotection of the Mtb/Mtz groups with 90% aqueous TFA in the presence of m-cresol and 2-methylindole gave the desired cionin derivative, which contains the tyrosine sulfate residue at the selective position. Yields obtained with approach (2) were considerably higher than those obtained with approach (1). Cionin and mono-Tyr(SO3H)-containing derivatives were assayed on exocrine pancreas in dogs. PMID- 8200740 TI - Hydrolysis pattern of procasomorphin by gut proteases from plant parasite Heliothis zea, determined by sequence analyses performed on the unfractionated digestion mixtures. AB - The digestion pattern of procasomorphin, a putative precursor of beta casomorphins (beta-casein-derived opioid peptides), by gut proteases from the plant parasite insect Heliothis zea has been determined to evaluate the possibility of introducing in plants the gene encoding for this peptide in order to confer resistance to damage by the insect. The method we used is based on the possibility of deducing the sequence of the fragments produced by proteases at different times of digestion by means of automatic Edman degradation performed on the fragment mixtures without any purification steps. This approach can be considered of general utility in studying the digestion of peptides by a mixture of proteases. PMID- 8200742 TI - beta-Carotene storage in rat organs following carrier mediated supplementation. AB - One rat group was supplemented with beta-carotene (BC) both in beadlets and the crystalline form in arachidic oil as a carrier added to standard diet; another rat group was given 1 ml crystalline BC-arachidic oil by gavage twice a week. In both rat groups, each rat ingested 350 mg BC/week for 12 weeks. The animals were then sacrificed and BC levels together with retinyl palmitate presence were assessed by HPLC analysis in liver, lung, kidney, small intestine, mesenteric fat, brain, spleen, stomach and blood plasma. In the first group, high BC storage, ranging from 4.2 to 45.2 nmols/g wet tissue, was found in liver, small intestine, spleen; lesser BC levels were found in lung, kidney, stomach, blood serum; retinyl palmitate was found in liver and lung. In the second group BC levels ranging from 0.5 up to 5,763 nmols/g wet tissue were detected in all organs, except for brain and stomach; the highest levels were in the lung; retinyl palmitate was detected in liver. The lung appeared to be a target organ for BC, as confirmed by its presence in the lungs of control rats fed standard diet and given 1 ml of arachidic oil alone by gavage twice a week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200744 TI - Maternal and cord serum vitamin E levels in normal and abnormal pregnancy. AB - The purpose of this study was to ascertain whether there is an association between reduced vitamin E levels and an abnormal pregnancy. Levels were measured by HPLC in maternal and, where possible, in paired umbilical cord serum from normal and abnormal pregnancies at delivery and in serial serum samples from healthy women during gestation. Abnormal pregnancies were compared with normals. In normal pregnancies, mean vitamin E levels rose from 12.9 +/- 1.1 micrograms/ml in early pregnancy to 22.5 +/- 1.5 micrograms/ml at term (p < 0.05, n = 11). In pregnancies with fetal complications or maternal risks, levels were lower than in normals at corresponding gestational age (p < 0.005 in smokers, n = 20 at > or = 30 weeks & p < 0.01 in hypertensives, n = 4 at 16-23 weeks). Mean maternal and paired cord serum levels in normal pregnancies at delivery > or = 37 weeks were 21.3 +/- 0.6 and 3.8 +/- 0.1 micrograms/ml respectively (p < 0.001, n = 56). Maternal levels in women with a low birthweight infant and in smokers (> 10 cig/day) were significantly lower (p < 0.05, n = 13 & p < 0.0005, n = 12); levels in women with a malformed infant (n = 6) were also reduced, but just barely below the level of significance (p = 0.06). Cord serum levels in complicated pregnancies, however, were unchanged. The results show lower maternal levels of vitamin E in abnormal pregnancies, suggesting a changed vitamin E metabolism. PMID- 8200745 TI - The role of vitamins A, beta-carotene, E and C in cancer cell biology. AB - Vitamins A (retinol, retinoids), beta-carotene (provitamin A), E (alpha tocopherol), and C (ascorbic acid) are used in experimental, clinical and epidemiological studies for cancer chemoprevention and treatment. The cellular and metabolic effects are depending on the dose used, duration of exposure, and cancer cell type. Despite recent advances, the anticarcinogenic mechanisms remain as yet unknown. Studies regarding the role of vitamins A, beta-carotene, E and C in cancer cell biology and metabolism are of critical importance for their use in cancer treatment. Autoradiographic, ultrastructural and cell surface studies demonstrated that vitamins A, E and C are strong regulator factors of cancer cell differentiation, cell regression, membrane biogenesis, DNA, RNA, protein, and collagen synthesis, as well as transformation of precancer cells into cancer cells. These vitamins exert cytotoxic and cytostatic effects, and may reverse the cancer cell to the normal phenotype. Interrelation of vitamins A, E and C with oncogenes and growth factors play an important role in cancer cell biology. The data presented in this review can provide new insights for the understanding of anticarcinogenic mechanisms, and a rationale for the use of vitamins A, E and C in cancer chemo-prevention and treatment. PMID- 8200743 TI - beta-Carotene increases monocyte numbers in peripheral rat blood. AB - The purpose of this study was to determine changes in leukocyte numbers in peripheral rat blood after varying dietary beta-carotene intake. Thirty male weanling Sprague-Dawley rats were fed ad libitum a vitamin A deficient defined nutrient chow, adequate in all other nutrients. Rats were randomly placed in a group with beta-carotene added to the chow as the vitamin A source. Group 1 was completely deficient, Group 2 had 1 microgram beta-carotene/g chow, the control group, and Group 3 received 25 micrograms beta-carotene/g chow. Before beginning the experimental diets and after two weeks, a blood sample was taken from the tail vein for a differential white blood cell count. Animals were sacrificed by cervical dislocation, and the spleen and thymus were removed and weighed. There was a statistically significant increase in monocyte numbers in Group 3, and a positive correlation between beta-carotene intake and monocyte numbers. Beta carotene may affect monocyte numbers, a potential mechanism of action in cancer prevention. PMID- 8200746 TI - Thiamin status in pregnancy as determined by direct microbiological assay. AB - Serum and red cell thiamin levels were assayed on a group of pregnant Australian women using an automated direct microbiological assay with Lactobacillus fermenti as the test organism. Two of 103 (1.9%) had serum thiamin levels below the reference range and 2 of 67 (3.0%) were found to have red cell thiamin levels below the reference range. Although the mean serum levels between trimesters were not significantly different, there was a significant decrease in the mean red cell thiamin in the third trimester. Repeat red cell thiamin assays on some of the women a number of weeks after the initial assay revealed a decrease ranging from 17.5% to 35.4% with a mean reduction of 27.8%. PMID- 8200747 TI - Biotin kinetics in serum of cattle after intravenous and oral dosing. AB - Single oral (p.o.) or intravenous (i.v.) doses of biotin were given to four cattle (400-450 kg body weight) in two consecutive tests two weeks apart. Dosages were p.o. 20, 40, 80 or 160 and i.v. 5, 10, 20, 40 mg biotin per 300 kg body weight. A three-compartment model was used to describe the course of serum concentrations with time. After i.v. administration, terminal half-lives of about 8 h were found. Areas under the curves were linearly related to both the p.o. and the i.v. doses. The systemically available fraction of the p.o. dose was 50 to 60%. On the basis of kinetic parameters, the biotin uptake via the feed was estimated to be 2.5 mg/day, which was about half of that estimated to be in the hay consumed. The data suggest that there was no relevant ruminal synthesis of biotin. PMID- 8200748 TI - Effects of prolonged aspirin or acetaminophen administration to rats on liver folate content and distribution. Relation to DNA methylation and S adenosylmethionine. AB - The study was aimed at determining the effects of longterm administration to rats of aspirin or acetaminophen (ACAP) on liver folate content and distribution as well as whether or not hepatocyte DNA was methylated at the end of the treatments. In addition, S-adenosylmethionine and S-adenosylhomocysteine hepatic concentrations were determined. In liver, aspirin or ACAP administration were not associated with important changes in total folate content or glutamic acid chain length distribution. DNA methylation assessed by comparing the extent to which DNA from livers of control or treated animals could be methylated in vitro using (3H-methyl)S-Ado Met as methyl donor, resulted in similar [3H] methyl incorporation into DNA regardless of the drug. The long-term administration of the analgesics did not result in significant changes in S-AdoMet/S-AdoHcy ratios. PMID- 8200749 TI - Effects of modifying dietary protein in the presence and absence of vitamin B6, on the regulation of plasma calcium and phosphorus levels--positive impact of yeast Saccharomyces cerevisiae. AB - Vitamin B6 status has been assessed according to the activation coefficient (AC) of plasma aspartic aminotransferase (AST) activity. Fast-growing male one-day-old broiler chicks, divided into two groups (supplemented with pyridoxine or not), were fed a soy protein isolate (Soyamin) or a purified amino acid diet containing or not Saccharomyces cerevisiae yeast (2%), primarily used to promote the growth of the B6-deficient animals. In one experiment, the protein level of the diet has been increased to augment the metabolic demand for PN. The B6-deficient Soyamin diet B containing yeast produced a mild deficiency (without incidence of morbidity and mortality) and the deficiency was severe (appearance of neurological symptoms after 10 days, AC 1.5) when yeast was deleted (diet A). The inclusion of yeast in both Soyamin and amino acid diets significantly increased plasma Ca and Pi levels (p < 0.001) whereas increasing the protein intake (diet C) had an inverse effect, reflecting an inhibitory effect on intestinal absorption of these minerals. Changes in plasma Ca and Pi levels due to dietary treatments were summarized in terms of their theoretical ion product. The amino acid diet D produced the lowest Ca x Pi ion product and the highest value was obtained with the yeast-containing diets B and E, regardless of the vitamin B6 intake and the dietary protein source. Plasma Ca and Pi levels were simultaneously elevated in severe vitamin B6 deficiency (diet A) as compared to control group (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200752 TI - Factors associated with low values of biochemical vitamin parameters in healthy subjects. AB - Levels of vitamins A, E, C, B1, B2, B6, B12, folate and beta-carotene were assessed in plasma or whole blood in a group of 114 healthy adults. Biochemical vitamin status was classified into acceptable or suboptimal (moderate or severe). The independent association of various factors with the finding of a suboptimal vitamin status was studied by means of logistic regression analyses. Seventy seven per cent of subjects had suboptimal vitamin status for vitamin B2, 20% for vitamin A, and 84% for beta-carotene. Although few subjects had suboptimal biochemical levels for vitamin E, plasma levels of this vitamin were significantly lower in smokers than in non-smokers (p < 0.01). Likewise, plasma folate levels were significantly related to body mass index and the season of blood sampling (p < 0.05). Old age was protective (OR 0.15; 95% CI 0.03-0.67), whereas current smoking was harmful (OR 3.63; 95% CI 1.09-12.1) for riboflavin status. Age group of 25-59 years was independently associated to a low risk of suboptimal vitamin A status (OR 0.29; 95% CI 0.09-0.88). On the other hand, female sex had a negative effect on plasma vitamin A levels (OR 2.39; 95% CI 0.82 6.92) and smoking had a harmful effect on biochemical beta-carotene status (OR 2.72; 95% CI 0.82-8.99). This cross sectional study provides information about the determinants of vitamin inadequacy, and may be the basis for further pathophysiological studies. PMID- 8200750 TI - The distribution of ascorbic acid and dehydroascorbic acid during tissue regeneration in wounded dorsal skin of guinea pigs. AB - The distribution of L-ascorbic acid AA and dehydroascorbic acid DHA in wounded and intact skin of guinea pig was investigated to elucidate the utilization of AA during tissue regeneration. Male guinea pigs fed an AA-free diet for 14 days were surgically injured on the dorsal skin, followed by intraperitoneal supplementation of AA (0.5, 5 and 50 mg/day/animal) for 4 days. The wounded skin, its surroundings and intact skin in each animal were removed for the determination of AA, DHA and collagen. The collagen content in wounded and intact skin increased in dose-dependent manner up to 5 mg AA/day, although neither the wounded nor the intact skin of the group supplemented with 50 mg AA had a higher content of collagen than those supplemented with 5 mg. In each group, the wounded skin had only about half the collagen of intact skin. AA content in the wounded skin of the groups supplemented with 5 and 50 mg AA were significantly lower than that in the other parts of their skin, whereas DHA content in wounded skin increased markedly. These results indicate that other factors besides collagen synthesis may enhance the oxidation of AA in the early stage of tissue regeneration. PMID- 8200751 TI - Vitamin activities in human portal, hepatic and femoral blood after vitamin ingestion. AB - The dynamics of intestinal absorption, blood concentration and distribution of thiamin, biotin, nicotinate, riboflavin, pantothenate, various folates (folic acid, folinic acid, pteroyltriglutamate), vitamins A, E, C, B12, and B6 were monitored in 12 patients by multiple simultaneous sampling of blood obtained by combined catheterization of portal vein, hepatic vein, and femoral artery after vitamin ingestion. All water-soluble vitamins proved elevated after vitamin ingestion principally in portal blood within 10 minutes as compared with hepatic and femoral blood. Elevated vitamin levels in portal blood--compared to hepatic and femoral blood--remained high even after 120 min. indicating that absorption from the gut was still progressing. In contrast, ingestion of the fat-soluble vitamins A and E evoked no elevated vitamin activity in portal blood. Within 10 min. after vitamin ingestion, all folates were converted into reduced and methylated 5-methyltetrahydrofolate (5-CH3THF) on passage through the gut. At this time, portal blood elevation of 5-CH3THF persisted before its elevation in hepatic or femoral blood. Presumably, the elevation was not due to the flushing of stored 5-CH5THF from tissues but rather of folate conversion to 5-CH3THF upon gut passage. The significance of these findings is discussed. PMID- 8200753 TI - Effects of dietary corn and olive oil versus coconut fat on biliary cholesterol secretion in rats. AB - We have studied the effects of dietary corn and olive oil versus coconut fat on bile formation and fluidity of hepatic plasma membranes in rats. After 4 weeks of feeding the purified diets containing 9% (w/w) of the test fats, there was no difference in plasma cholesterol concentration between the dietary groups. The amount of free and esterified cholesterol in the liver was significantly higher in rats fed either corn oil or olive oil as compared with coconut fat. In the rats fed olive oil, but not in those fed corn oil this was associated with lower rates of biliary phospholipid excretion. Bile flow was not differently influenced by the three dietary fats. Hepatic plasma membranes of the rats fed corn or olive oil contained more cholesterol and less phospholipids than those on coconut fat, which was, however, not accompanied by changes in fluidity of the membranes. These results indicate that in rats the type of dietary fat can induce considerable changes in hepatic cholesterol metabolism without affecting plasma cholesterol concentrations, and without consistent effects on biliary cholesterol secretion. PMID- 8200754 TI - Plasma amino acids changes in obese patients on very low-calorie diets. AB - The reduced feeling of hunger alleged by obese patients on very low-calorie diets (VLCD) could be supposed due to restoration to a normal level of plasma TRP:LNAA ratio, previously found lowered in these subjects. We tested this hypothesis measuring weekly the changes of plasma amino acid concentration in obese individuals who followed a 5 week slimming regimen consisting in a powdered formula diet (500 kcal/d). A decrease in plasma TRP:LNAA ratio was seen, since tryptophan decreased, whereas valine and isoleucine increased over time. An increase in plasma lysine, threonine, glycine and aminobutyrate was also observed. The early decrease shown by alanine and glutamate was followed by an increase in the last weeks of the study. Our hypothesis was not confirmed, since VLCD failed to carry back the plasma TRP:LNAA ratio to a normal level. PMID- 8200755 TI - Vitamin A levels in bovine and pork liver. PMID- 8200756 TI - [Controversies in therapy of malignant lymphomas]. PMID- 8200758 TI - [Liver transplantation as practiced gene therapy. A controversy]. PMID- 8200757 TI - [Controversies in prevention and therapy of thromboses and embolisms]. PMID- 8200759 TI - [Controversies in the treatment of benign thyroid gland diseases]. PMID- 8200760 TI - [Controversies in therapy of portal hypertension and bleeding esophageal varices]. PMID- 8200761 TI - [Controversies in therapy of acute myocardial infarct]. PMID- 8200762 TI - [Controversies in therapy of bronchial asthma]. PMID- 8200763 TI - [A 27-year old patient with watery diarrhea, nausea and vomiting 10 hours after eating a mushroom dish. Interdisciplinary liver transplantation team of the Grosshadern Clinic]. PMID- 8200765 TI - [Acute therapy of anaphylactoid reactions. Results of an interdisciplinary consensus conference]. PMID- 8200766 TI - [Periodontitis: periodontal diseases]. PMID- 8200764 TI - [Recurrent burning pain, erythema, cutaneous edema and hyperthermia of both lower legs after herpes zoster thoracalis]. PMID- 8200767 TI - [Alkaline phosphatase reduced to 30 u/l]. PMID- 8200768 TI - [Fever of uncertain origin]. PMID- 8200769 TI - The short bowel syndrome: underdiagnosis or undertreatment? PMID- 8200770 TI - Successful pregnancy in I.D.D.M. with intravenous programmable insulin pump. AB - Management of subcutaneous insulin resistance remains a difficult problem which can be treated by administering insulin intravenously by means of infusion pumps. We wish to report the case of a 31 year old primigravida with subcutaneous insulin resistance who developed a hitherto undescribed clinical complication of clot formation at the catheter tip, successfully treated with anti-coagulant therapy. Previous publications on the use of pumps in pregnancy have reported on the intraperitoneal route for insulin administration. PMID- 8200771 TI - A survey of the work practices of physiotherapists in the community. AB - The aim of this study was to find out what kind of physiotherapy service is available in the community. Two groups were studied (i) private practitioners and (ii) community physiotherapists employed by health boards. The results indicate that the private practitioners provide a service in the community to a mainly young, or middle-aged and mobile population. The conditions treated were mostly of an acute nature, viz. sports injuries, low back pain and whiplash injuries. The community physiotherapy service provided by the health boards served mainly the very young, i.e. 0-15 years and the elderly. The conditions seen were mostly long-term, viz. strokes and cerebral palsy. The community physiotherapist saw 50% of cases in the patient's own home, while the private practitioners saw 93% of cases in the practice premises. PMID- 8200772 TI - An outbreak of parvovirus B19 infection; a study of clinical manifestations and the incidence of fetal loss. AB - Eighty-five cases of B19 infection were diagnosed in Northern Ireland from 1984 to 1989; 65 of these occurred during 1989, the outbreak year. Of the total 85 cases, 15 had a rash, 21 had arthralgia, 47 had a rash and arthralgia, and 2 had aplastic crisis. The age range was 4-63 years with a mean of 26.9 years. Thirty cases (35%) were referred to hospital; 25 of these had arthralgia and 2 had aplastic crisis. Two thousand four hundred pregnant women at 12 weeks gestation in 1989 were screened for anti-B19 IgM; 8 were positive. Of these 8 patients, 7 progressed to delivery of a normal fetus and one had an intra-uterine death at 26 weeks gestation; no congenital abnormalities were noted in any fetus. The incidence of fetal involvement in maternal B19 infection in this study was therefore 12.5%. PMID- 8200773 TI - Intensive care medicine in Ireland. PMID- 8200774 TI - Guidelines for the use of thrombolysis in acute myocardial infarction--second consensus report 1994. Council on Acute Coronary Care of the Irish Heart Foundation. PMID- 8200775 TI - Perioperative creatine phosphokinase trends in elderly patients with hip fracture. AB - A prospective study of the serum levels of unfractionated creatine phosphokinase (CPK) in 69 consecutive elderly patients undergoing surgery for hip fracture is reported. Serum unfractionated CPK levels were measured on admission, on the evening following surgery and daily for the first five days post-operatively. All of the CPK levels measured on admission were within the normal range for this laboratory. A gradual rise in CPK levels followed surgery. On the evening following surgery 75% of values were greater than the upper limit of the normal reference range. The peak values were seen on day 1 post-operatively but 25% of values were still less than the reference maximum. A gradual decline was seen after this and at day 5 post operatively 50% of values were within the normal reference range. A single unfractionated CPK determination is not of diagnostic benefit in the post-operative period in elderly patients with hip fracture. However, patients with intracapsular and intertrochanteric fractures do not show elevation of unfractionated CPK levels prior to surgery. PMID- 8200776 TI - Primary amelanotic malignant melanoma of the oesophagus--a case report. PMID- 8200777 TI - Prevalence and forms of neuropathic morbidity in 800 diabetics. AB - We prospectively determined the prevalence of morbidity from the various forms of diabetic neuropathy over one year in a population of 800 patients with diabetes mellitus (336 type 1, 464 type 2 DM). Symptoms documented were: pain/paraesthesia in the feet, loss of feeling and the restless legs syndrome. We also documented the prevalence of: neuropathic ulcers, amyotrophy, foot drop, and oculomotor palsy. Autonomic symptoms documented were: impotence, postural hypotension and diarrhoea. The only symptoms reported by 100 non-diabetic control subjects were: loss of feeling in 2% and restless legs syndrome in 7%. In the diabetics; pain/paraesthesia was present in 13%, feeling loss in 7% and neuropathic ulcers in 2%. The prevalence of Diabetic amyotrophy (proximal femoral neuropathy) was 0.8%, oculomotor palsy 0.1% and peroneal nerve palsy 0.1%. Erectile impotence was present in 20%, symptomatic postural hypotension in 1% and diabetic diarrhoea in 1%. Overall; 22.9% of the population was afflicted by one or more problems resulting from neuropathy. Neuropathy was associated with older age (p < 0.001), and serious retinopathy (p < 0.001) in both groups of diabetics and with duration of diabetes, proteinuria (p < 0.02), hypertension (p < 0.01) and ischaemic heart disease (p < 0.02) in type 1 diabetics. PMID- 8200778 TI - Patient exposure to ionising radiation in the intensive care unit due to portable chest radiography. AB - The chest X-ray is the most commonly performed radiological examination in the intensive care unit. We used TLDs to measure the radiation exposure in 30 ICU patients due to portable chest radiography. The mean number of CXR was 3 (range 1 11). The mean surface entry dose at the xiphisternum was 1.8 mGy (range 0.43-5.14 mGy) per patient and 0.63 mGy per CXR. Very small amounts of radiation were detected at the symphysis pubis and in more than half of the patients no radiation was detected at this site. These values are well above accepted norms. Patient exposure may be reduced by ordering fewer X-rays or by changing to a faster screen-film combination. PMID- 8200780 TI - Scintigraphic characterisation of ossific metastases in osteosarcoma. PMID- 8200779 TI - Laparoscopic appendicectomy--review of the first decade. PMID- 8200782 TI - Alcohol content of proprietary mouthwashes. AB - The use of mouthwashes with high ethanol content has been linked to excess risks of mouth cancer, as have prolonged and frequent use of mouthwashes with lower ethanol contents. Twenty two proprietary mouthwashes available without prescription in Ireland were analysed by gas chromatography and their ethanol contents (w/v) at manufacturers' recommended dilutions for use were calculated. The ethanol contents of diluted mouthwashes ranged from < 0.01-23.40% w/v. 27% had ethanol contents > 10% w/v; 9% had ethanol contents > 20% w/v. As the use of the higher ethanol content mouthwashes may be a possible risk factor for oral cancer in frequent or constant users, we believe that the attention of the statutory regulatory authorities should be drawn to this situation. PMID- 8200781 TI - Riedel's thyroiditis--case report and literature review. AB - A fifty two year old female underwent attempted thyroidectomy for a progressively enlarging cervical swelling. At operation the thyroid gland was extensively fibrosed and not resectable, frozen section showed fibrous replacement. The patient was given a short course of postoperative corticosteroid therapy and was maintained on thyroid replacement therapy. Thirty months later the patient remains asymptomatic. PMID- 8200784 TI - Sedation for non-invasive procedures: a potential hazard. PMID- 8200783 TI - Post-myocardial infarction ventricular septal defect: an angiographic study. AB - Clinical and angiographic findings are reported in a consecutive series of nineteen patients with post infarction ventricular septal defect (PIVSD). In all patients PIVSD complicated a first myocardial infarct and none had a history of angina pectoris prior to presentation. In over 50% of the patients PIVSD occurred within three days of infarction. The mean patient age was 65 years. Single vessel disease was noted in 63% of the patients. The mean left ventricular ejection fraction was 27%. Contrast left ventriculography localised the defect in all patients. Although a comprehensive cardiac ultrasound examination will generally confirm the diagnosis of PIVSD, preoperative coronary angiography is essential for the selection of those patients most likely to benefit from concomitant coronary artery bypass grafting at the time of surgical repair of the interventricular septum. PMID- 8200785 TI - How cluster headache is explained as an intracavernous inflammatory process lesioning sympathetic fibers. AB - A large body of evidence points to an inflammatory process in the cavernous sinus and tributary veins as being primarily responsible for cluster headaches. The inflammation obliterates the venous outflow from the cavernous sinus on one side and injures the through-running sympathetic fibers to the eye, upper eye lid, forehead skin, and the intracranial internal carotid artery and its branches. The active period ends when the inflammation is suppressed and the sympathetic fibers partially or fully recover. Evidence is presented that the symptoms suggestive of an enhanced parasympathetic activity during attacks may alternatively be explained as local pain fiber activation or a stasis in the outflow from the cavernous sinus. Vasodilator agents like nitroglycerin induce an attack by enhancing the venous load on the cavernous sinus. Constriction of the proximal intracranial internal carotid artery, spontaneously induced by stressful pain activation of the perivascular sympathetic nerves, or by exogenous administration of serotonin 1D-like receptor agonists or oxygen, terminates the venous load and thus the pain and associated symptoms. PMID- 8200786 TI - The diagnosis of headache in primary care: factors in the agreement of clinical and standardized diagnoses. AB - OBJECTIVE: Comparison of clinical headache diagnoses in primary care to algorithm diagnoses from a standardized headache interview. DESIGN: A sample of consecutive primary care headache patients (n = 779) at the Group Health Cooperative of Puget Sound were interviewed and medical records abstracted. MEASUREMENTS: The medical record provided 'chart' diagnoses while a structured interview and diagnostic algorithm yielded the 'algorithm diagnosis'. The patients were also administered the depression sub-scale from the SCL 90-R, in addition to answering questions about pain intensity and disability used to grade the severity of chronic pain. RESULTS: Among persons diagnosed by the primary care physician as having migraine, 78% received an algorithm diagnosis of migraine. However, study patients were more likely to receive a diagnosis of migraine by algorithm (57%) than by clinical diagnosis (33%). While clinicians infrequently recorded a diagnosis of migraine and tension-type headache in the same patients, tension type headache was identified among half of the algorithm diagnosed migraineurs. Among patients with algorithm-diagnosed migraine, female gender, increased disability, and the presence of aura increased the likelihood that the clinician would also diagnose migraine. Conversely, the presence of tension-type headache features, high levels of depression, high number of headache days and age over 65 years reduced the likelihood of the clinician diagnosing migraine among algorithm diagnosed cases. CONCLUSIONS: The co-occurrence of migraine and tension-type headache symptoms are commonly reported by patients, however, primary care physicians usually recorded a single diagnosis of either migraine or tension headache. Among patients reporting migrainous features, the presence of chronic headache, emotional distress and the absence of disability reduced the likelihood that the clinician would assign a diagnosis of migraine. These results suggest the need for diagnostic and management strategies appropriate for patients whose headaches combine tension-type and migrainous features. PMID- 8200787 TI - Does quality of life differ among headache diagnoses? Analysis using the medical outcomes study instrument. AB - BACKGROUND: To analyze the differences in quality of life associated with headache diagnoses using the Medical Outcomes Study Short Form Health Survey (SF 20). METHODS: A patient interview survey using the SF-20 Short Form Health Survey was conducted in a headache clinic within a multi-specialty group practice. All six health components of the SF-20 were included in the study. Headache diagnoses were made using IHS criteria. RESULTS: 208 consecutive headache patients were studied. Patients with cluster headache had a significantly higher (worse) pain score (P < 0.018) and higher percentage of patients with poor health due to pain (P < 0.005) than patients with migraine headache. There were fewer cluster patients with poor health associated with physical functioning than tension-type (P < 0.020) or mixed headache (P < 0.022) patients. Poor health associated with social functioning was greater for cluster (P < 0.011) and tension-type headache (P < 0.015) than for migraine. There was a significantly higher percentage of tension-type headache patients with poor health associated with mental health (P < 0.002) than patients with migraine. CONCLUSIONS: The SF-20 is a reliable and valid measure of quality of life for patients with different headache diagnoses. Distinct headache diagnoses are marked by unique patterns of impairment and quality of life. PMID- 8200788 TI - Use of dihydroergotamine in patients with postconcussion syndrome. AB - The experience with 34 patients who came to the Shreveport Headache Clinic for treatment of postconcussion headache is reviewed. All had been suffering from postconcussion (posttraumatic) syndrome for periods ranging from one day to more than three years, and all displayed, in addition to headache, at least three other symptoms characteristic of the syndrome, eg, memory problems, impaired concentration, sleep problems, dizziness, and anxiety. After initial evaluation at the clinic, the patients were admitted to Willis Knighton Medical Center and treated with repetitive administration of intravenous dihydroergotamine (DHE) and metoclopramide. A good to excellent overall response to DHE therapy was achieved by 88% (29) of the patients. The percentages and numbers of patients obtaining good to excellent relief of selected key symptoms were: 85% (28) - headache, 91% (30) - memory problems, 94% (31) - sleep problems, and 88% (29) - dizziness. DHE was well-tolerated, and no serious or unexpected adverse reactions were reported. The most frequently reported adverse reactions were mild nausea and brief worsening of headache. PMID- 8200789 TI - MMPI profiles of Turkish headache sufferers. AB - The investigations of personality traits have been the issue of many studies on patients with headache. Minnesota Multiphasic Personality Inventory (MMPI) is the most popular assessment instrument used in these studies. MMPI responses of 36 cases (14 male, 22 female) with tension headache and 44 cases (11 male, 33 female) with migraine headache had been compared with 36 nonheadache controls (12 male, 24 female). Because of the inadequate number of male subjects, the statistical analyses were made between female groups. The results obtained revealed that subjects in the tension-type headache group got significantly higher scores on neurotic subtests (hypochondriasis, depression, hysteria) than subjects in the control group. Likewise, migraine subjects got significantly higher scores on hysteria subtest than control subjects. No significant differences were noted between migraine and tension groups. However, none of the headache groups could be characterized by marked elevations on any of the validity and clinical scales. These results, support the finding that neurotic symptoms occur with a higher frequency in headache sufferers. PMID- 8200790 TI - Headache and electroconvulsive therapy. AB - While headache is a documented side effect of electroconvulsive therapy (ECT), there is little information on this phenomenon. Studies of the mechanisms of ECT as a treatment for depression indicate that alterations in serotonergic neurotransmission appear to be related to its efficacy. While ECT and many of the antidepressant drugs have similar effects on serotonergic transmission, they are notably different in the changes they induce in type 2 receptors for 5 hydroxytryptamine (5-HT). ECT upregulates 5-HT2, and antidepressants down regulate the receptor's expression. 5-HT2 receptor sensitization has been associated previously with headache genesis, which may explain why ECT induces headache, and amitriptyline relieves headache. In our study we surveyed 98 patients retrospectively about their experiences with headache prior to and following ECT. Of the 54 patients who submitted properly completed questionnaires, five reported new onset of headaches following ECT, four reported exacerbation of a previous headache problem, and two reported their headaches improved. The patients experienced changes in the character or location of pain, with a tendency to progress from tension-type to migrainous headache. In all but two cases these developments persisted at least eight months after ECT. We discuss the possible reasons and significance of our findings. PMID- 8200791 TI - Magnesium content of mononuclear blood cells in migraine patients. AB - Recent research has shown that magnesium levels in serum, salivary secretions and red blood cells are reduced in migraine patients with and without aura, both ictally and interictally. This suggests that lower magnesium levels can contribute to the etiopathogenetic mechanisms underlying migraine attacks. It has been suggested that mononuclear magnesium content is a reliable index of magnesium nutritional status, as it is more closely related to the total body stores than other biochemical indices. Therefore we determined mononuclear magnesium content in adult migraine patients with and without aura, in headache free periods and, in a number of patients, during attacks. Migraine patients with and without aura, assessed in interictal periods, had a reduced mononuclear magnesium content compared to age-matched healthy control subjects. No significant variations were observed between ictal and interictal periods in migraine patients with aura and without aura. The lower magnesium content in mononuclear cells could indirectly indicate the reduction of brain magnesium concentration, which has recently been demonstrated in the course of migraine. PMID- 8200792 TI - 1044 women with migraine: the effect of environmental stimuli. AB - This study initiated by a self-help migraine group investigated disability caused by visual environmental stimuli, e.g. glare, flicker, pattern and color. One thousand forty-four women with migraine completed the self-report questionnaire on visual environmental stimuli reported in earlier studies to precipitate or aggravate migraine. One hundred twenty-one female controls were obtained from general practice and hospital out-patients. The responses of the classical, common and non-migraine groups were compared. Women with classical migraine expressed greater disability than those with common migraine or controls both in respect of number of visual sensitivities reported (P < 0.0001) and severity of consequences of such stimuli (P < 0.0001). This study indicated differences between classical and common migraine outside of the attack phase apart from aura. Reported range of sensitivities for the migraineurs peaked between the ages of 46-60 years. A high level of unrealized disability caused by visual environmental stimuli was thus identified in hitherto unexplored self-help groups. PMID- 8200793 TI - Limb pain and headache. AB - The occurrence of limb pain in close temporal relationship with headache was sought in 245 (185 women and 60 men) patients. Eleven patients (4.4% three men and eight women) had referred pain at least once, in one or more limbs in close temporal relationship with headache. Usually the pain was located in the upper limbs, was concomitant with the headache but could precede or follow it. The severity and length varied between patients but was relatively stable in the same subject. It is possible that this symptom is more frequent than believed so far and that many patients are misdiagnosed. PMID- 8200794 TI - Acute headache of recent onset and subarachnoid hemorrhage: a prospective study. AB - Twenty-seven patients with acute severe headache of recent onset were prospectively recruited in the Emergency Room. Mean duration of headache was 61 hours. CT scan disclosed subarachnoid bleeding in 4 patients and spinal tap revealed subarachnoid hemorrhage (SAH) in 5 patients with normal CT scan. In most SAH cases pain was bilateral, very intense and involving the occipital region. Four of these patients had doubtful or no nuchal rigidity and in one, pain improved while in the Emergency Room. In every case with an intense acute severe headache of recent onset CT scan and (if normal) a lumbar puncture are warranted to help rule out a SAH. PMID- 8200796 TI - The effect of solubility on inhaled uranium compound clearance: a review. AB - Research on inhaled industrial uranium compounds has shown that solubility influences the target organ, the toxic response, and the mode of uranium excretion. Consideration of physical chemical properties indicates that the dissolution of industrial uranium oxides is expected to be strongly dependent on process history, and that dissolved uranium exists in vivo in the hexavalent state regardless of the oxidation state of the inhaled compound. The overall clearance rate of uranium compounds from the lung reflects both mechanical and dissolution processes. Mechanical clearance rates are highly variable among individual workers studied, but dissolution rates of inhaled compounds are similar among the mammalian species studied. Results from experiments in vivo and accidental worker exposures indicate that the uptake of dissolved uranium from the lung is more rapid than the dissolution rate of most industrial uranium compounds. These results indicate that the absorption rate of inhaled uranium can be approximated by the dissolution rate of most industrial compounds. Dissolution rates of UF6 and UO2(NO3)2 are more rapid than the mechanical clearance rates and dominate the overall lung clearance rate. UF4, UO3, and ammonium diuranate have intermediate dissolution rates that are similar to mechanical clearance rates and exhibit high variability among uranium specimens. U3O8 and UO2 have slow dissolution rates such that pulmonary clearance rates are dominated by mechanical processes. Industrial uranium ores, oxides, and fluorides are often variable mixtures of relatively soluble and insoluble fractions. Dissolution rates measured in vitro can be used with biokinetics models to reduce the uncertainties in dosimetry associated with inhalation exposures to mixtures. PMID- 8200795 TI - Computed tomography in the routine evaluation of headache. PMID- 8200797 TI - Probability of causation for lung cancer after exposure to radon progeny: a comparison of models and data. AB - The estimates of lung cancer risk due to the exposure to radon decay products are based on different data sets from underground mining and on different mathematical models that are used to fit the data. Diagrams of the excess relative rate per 100 working level months in its dependence on age at exposure and age attained are shown to be a useful tool to elucidate the influence that is due to the choice of the model, and to assess the differences between the data from the major western cohorts and those from the Czech uranium miners. It is seen that the influence of the choice of the model is minor compared to the difference between the data sets. The results are used to derive attributable lifetime risks and probabilities of causation for lung cancer following radon progeny exposures. PMID- 8200798 TI - Propagation of variance uncertainty calculation for an autopsy tissue analysis. AB - An assay value is almost useless unless it is accompanied by a measure of the uncertainty associated with that value. The uncertainty value should reflect all the major sources of variation and bias affecting the assay and should provide a specified level of confidence (for example, 95%). An approach to uncertainty calculation that includes the uncertainty due to instrument calibration, values of the standards, and intermediate measurements as well as counting statistics is presented and applied to the analysis of an autopsy tissue. This approach, usually called propagation of variance, attempts to clearly distinguish between errors that have systematic (bias) effects and those that have random effects on the assays. The effects of these different types of errors are then propagated to the assay using formal statistical techniques. The result is an uncertainty on the assay that has a defensible level of confidence and which can be traced to individual major contributors. However, since only measurement steps are readily quantified and since all models are approximations, it is emphasized that without empirical verification, a propagation of uncertainty model may be just a fancy model with no connection to reality. PMID- 8200800 TI - Measurement of the attenuation coefficient for Livermore Thoracic Phantom lungs fabricated using contemporary materials. AB - The University of Cincinnati has reproduced the original formulation for the Livermore Thoracic Phantom lungs using contemporary materials and has adopted the linear attenuation coefficient as the primary quality assurance parameter for evaluating the performance capabilities of these new lung phantoms. The Livermore Thoracic Phantom was originally fabricated in 1978 to intercalibrate detector systems used to measure plutonium and other low-energy, photon emitting radionuclides deposited in the respiratory tract. The linear attenuation coefficient is a critical performance indicator for these phantom lungs since the presence of any material with a high effective atomic number (where Z > or = 20) will make a significant change in the photoelectric cross section, the predominant mode of interaction for plutonium x rays. A set of test lungs was fabricated with KCl to introduce a known quantity of 40K in the phantom and to determine, by measurement and calculations, what change would be made to the attenuation coefficient at photon energies below 100 keV as a result of the modified formulation. The KCl increased the linear attenuation coefficient below 60 keV by more than a factor of two, which would produce a substantial systematic error in any subsequent calibration measurements performed with these modified phantom lungs. These results support use of the attenuation coefficient as an important performance indicator for the Livermore Thoracic Phantom lungs and also suggest that KCl not be added to the lung tissue substitute formulation as a means to incorporate 40K in the phantom for low energy calibrations. PMID- 8200799 TI - Radiation protection and radioactive scales in oil and gas production. AB - Low specific-activity scales consisting of alkaline earth metal carbonates and sulfates are often present in some gaseous and liquid hydrocarbon plants. These scales contain a certain concentration of radium, uranium, and thorium which can cause a risk of gamma irradiation and internal radiocontamination when they must be mechanically removed. The gamma dose rates and the 238U, 232Th, 226Ra concentrations were determined in sludges, scales, and waters of some gas and oil hydrocarbon plants located in Italy, Congo, and Tunisia. 238U and 232Th concentrations were were low. The isotopes 238U and 234U resulted in radioactive equilibrium, while 232Th and 228Th were not always equilibrium. A rough correlation was found between the gamma dose rate and the 226Ra concentration. Some considerations and conclusions about radiation protection problems are pointed out. PMID- 8200801 TI - Probabilistic consideration of consequences of long-duration accidental releases based on complete weather data. AB - This paper presents a method based on chronological weather data for estimating how variations in weather conditions during a radioactive release affect the consequences of the release. The modifications of the method made in the computer based applications owing to the limited calculation resources are also studied. Additionally, the length of the chronological weather data observation period needed to satisfactorily support the assessments was tested. The results of the different duration times for the normalized concentration--which is the concentration divided by the release rate, and called here the dispersion factor- are presented and compared with the commonly used sector average model and the generic wind meandering method. The new method can be used for a variety of release durations and it makes realistic estimates, managing to avoid the weaknesses of the methods compared. The necessary length of the weather data is on the order of 1 y to get statistically satisfactory results. PMID- 8200802 TI - Partitioning of 222Rn entry into a structure surrounded by soil. AB - This paper describes the entry rate of 222Rn into a basement structure surrounded by a sandy clay loam soil. The highest indoor radon concentrations occurred when the rate of entry was lowest. Data from in-situ measurements were used to identify the entry pathways and also the origins of the radon during periods when the entry rate was low. Results indicated that 25% of the radon entered through the floor-wall joint and 75% through the floor and walls. About 30% of the radon originated in the concrete. Diffusion was the primary transport mechanism. However, radon entry through the floor-wall joint was a combination of diffusion and a convective flow between the subslab region and the interior of the structure. PMID- 8200803 TI - Theoretical considerations regarding the migration of 222Rn and 220Rn from uranium- and thorium-bearing underground environments. AB - Theoretical calculations are presented for partially enclosed uranium- and thorium-bearing subterranean environments, such as tunnels and underground uranium mines. The variables of practical interest considered here are the 222Rn and 220Rn concentrations in the wall, and the flux densities of the same radioactive gases in the wall and at the wall/air interface of these underground sites. Calculations have been conducted based on a plane, semi-infinite geometry model (commonly used to predict radiation levels in mines) and a cylindrical (i.e., tunnel) geometry model. The 220Rn flux density, J(220Rn), calculated according to the plane and cylindrical geometries agree with each other within 5% for wall media of porosity equal to or greater than about 2%, even for tunnels of small radii. However, for 222Rn the cylindrical geometry gives values for the 222Rn flux density, J(222Rn), substantially higher (by a factor of 1.4 to approximately 3) than those predicted by the plane semi-infinite geometry. A practical difficulty arises in the experimental verification of the models in underground environments. The results are relevant for predicting radioactivity levels (222Rn, 220Rn, and their progeny) in underground environments such as uranium mines. Health Phys. PMID- 8200804 TI - Stochastic variability in effective dose tissue weighting factors: a Monte Carlo study. AB - Tissue-weighting factors used in the calculation of the effective dose have undergone revision in the light of new data from the atomic bomb survivors. A Monte Carlo simulation was designed to evaluate the magnitude of stochastic errors in the derived factors. Results demonstrate substantial variability in the suggested factors. PMID- 8200805 TI - The significance of dose rate in assessing the hazards of domestic radon exposure. AB - Both miner-based epidemiological data and animal studies suggest that lung cancer induction from radon-progeny alpha-particle exposure depends on the exposure rate, and increases as the exposure rate decreases. This phenomenon has been interpreted to imply that radon risks per unit dose from domestic exposure (which occur at low exposure rates) will be underestimated by risk estimates derived from miner studies (which are at higher exposure rates). There is, however, another variable affecting this phenomenon, namely the absolute cumulative exposure to radon progeny. On basic biophysical grounds, it is argued that when the cumulative exposure is sufficiently low that multiple traversals of target cells are rare, the exposure rate effect disappears. This is the case for typical domestic radon exposures but not for most miner exposures; thus, although risk estimates from miner data refer to higher dose rates, based on dose rate consideration alone they may well overestimate, rather than underestimate, domestic radon risks. Although the data are limited, both miner-based epidemiological data and animal studies appear to follow the trend described here. PMID- 8200806 TI - Decommissioning of a university research reactor. AB - The objective of the UCLA Boelter Reactor Decommissioning Project was the release of the Boelter reactor facility for unrestricted use. The facility included a 100 kW Argonaut type research reactor that operated from 1963 to 1985, providing general reactor research. The decommissioning was planned as a two-phase program. Phase I involved removal of the reactor core structure for better access and assessment of the biological shield. Phase II decommissioning activities included structural steel removal, activated concrete removal, process equipment pit piping dismantlement, and clean concrete removal. The final release survey of the Boelter reactor facility demonstrated that all areas satisfied the project's release criteria. The total person-Sv for the project was 3.87 x 10(-2) (3.87 person-rem), most of which was received during the structural steel and activated concrete removal tasks and the disassembly of the reactor core. PMID- 8200807 TI - Effective dose to personnel wearing protective aprons during fluoroscopy and interventional radiology. PMID- 8200808 TI - Experts review Chernobyl status. PMID- 8200809 TI - Portable blood glucose monitors. PMID- 8200811 TI - Sparking during discharge testing on Physio-Control Lifepak 9 defibrillator/monitors. PMID- 8200810 TI - Fire caused by improper disposal of electrocautery units. PMID- 8200812 TI - Problems related to EtO sterilization of infant oxygen hoods. PMID- 8200813 TI - Properties of Drosophila simulans strains experimentally infected by different clones of the bacterium Wolbachia. AB - Maternally inherited bacteria of the genus Wolbachia are responsible for reproductive incompatibilities between strains of Drosophila simulans. Such incompatibilities are known in several types of crosses, including both directions of crossing between two types of infected strains, 'R' and 'S'. To determine whether the bidirectional incompatibility between R and S flies is due only to differences between their bacteria, flies from an uninfected strain have been experimentally infected with bacteria associated with each type. The incompatibility properties of experimental strains are close to those of original strains harbouring the same bacteria and therefore independent of nuclear background. Backcross experiments, however, show that the infection level of a strain depends on the nature of paternal ancestors. This is not explained by nuclear effects but is possibly the result of an interaction between the infection levels of both parents, in which the infection level of S strains is an equilibrium between a tendency for females to produce weakly infected offspring and selection of more infected eggs by sperm from infected males. PMID- 8200814 TI - Regulatory differences in developmental expression of alcohol dehydrogenase are related to interspecies differences in ethanol tolerance of Drosophila. AB - Biochemical properties and expression patterns of alcohol dehydrogenase were compared among members of the virilis phylad of Drosophila. Quantitative differences in stage- and tissue-specific expression of ADH of D. virilis, D. novamexicana, D. texana and D. americana were observed. These differences seem to correlate with the temporal differences in ethanol tolerance among these species. Quantitative differences in ADH protein levels account for most, if not all, of the activity differences between species. Analysis of the interspecific hybrids revealed that these differences arise by a mechanism affecting monomer synthesis. A comparison with earlier studies, where independently evolved regulatory differences were related to adaptations, revealed contrasting underlying mechanisms. PMID- 8200815 TI - Genotype-specific habitat selection for oviposition sites in the cactophilic species Drosophila buzzatii. AB - Isofemale lines of the cactophilic species, Drosophila buzzatii, exhibit genetic variation for their oviposition response to cactus yeast species in the laboratory. In general, interactions between yeast species preclude the use of pairwise preferences as predictors of preferences in three-way choice experiments. Two isofemale lines with relatively high laboratory preference for ovipositing on the yeast Pichia cactophila (as opposed to Cryptococcus cereanus) and two isofemale lines with relatively low preference for P. cactophila were used in a series of field release experiments to determine if laboratory preferences were also realized under field conditions. The influence of yeast species on both settling behaviour (long-distance response) and oviposition preference (short-distance response) were tested. The four lines were identical in their settling behaviour, preferring P. cactophila. The analysis of the oviposition preference tests showed significant line effects which correlated with the laboratory results. Thus a genetic component for oviposition preference under laboratory and field conditions was demonstrated and this strengthens the evidence for genotype-specific habitat selection in D. buzzatii. One low line, however, did not differ significantly from the two high lines under field conditions. A laboratory retest of this low line showed that the laboratory preference had not changed. The reason for the difference in the two situations is unknown but undoubtedly is attributable to uncontrolled variables under the field situation. Settling behaviour and oviposition response, in general, appear to be proximately linked to differences in the volatiles produced by the different yeast species. PMID- 8200816 TI - Geographical origin of an introduced insect pest, Listronotus bonariensis (Kuschel), determined by RAPD analysis. AB - The Argentine stem weevil, Listronotus bonariensis (Kuschel) (Coleoptera: Curculionidae), is an important introduced pasture pest in New Zealand. In this study geographical populations of this species were analysed using polymerase chain reaction-based randomly amplified polymorphic DNA (RAPD), in an attempt to determine the geographical origin of the pest. Morphologically indistinguishable individuals were collected from nine South American, five New Zealand and one Australian populations. Ten primers were screened for usefulness, two of which revealed significant, scorable polymorphisms between these populations. The results indicated that the sampled New Zealand L. bonariensis populations originated from the east coast of South America. PMID- 8200817 TI - Elderly abuse: the silent violation. PMID- 8200818 TI - Effects of osteopathic manipulative treatment in patients with cervicothoracic pain: pilot study using thermography. AB - To provide information on how cervicothoracic pain responds to osteopathic manipulative treatment, five subjects with acute or chronic pain received appropriate medication and three osteopathic manipulative treatments by the principal investigator using thrust and nonthrust techniques. The mean number of findings by both investigators on structural examination decreased considerably immediately after each of the three treatments. The number of findings increased in week 2 and decreased in week 3. The principal investigator observed a further decrease by the final session, but the coinvestigator reported an increase. The pain scale score improved an average of nearly 30%. Thermography showed cooling of the cervicothoracic region in all subjects and conversion to a normal pattern in four. Osteopathic manipulative treatment should be considered for patients with acute or chronic cervicothoracic pain. The use of thermographic analysis in clinical osteopathic research seems warranted. PMID- 8200821 TI - False-positive malignant peritoneal cytology associated with pelvic endometriosis. AB - The peritoneal washings obtained at diagnostic laparoscopy of two women with suspected endometriosis contained cells with cytologic features of adenocarcinoma. Exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic washings confirmed endometriosis with no evidence of cancer. At 1.5-year and 4.0-year follow-up, respectively, cancer had not developed in either patient. The authors report what they were able to find in the literature regarding false-positive assessments of malignancy obtained by cytologic examination. They also outline steps to be taken should a diagnosis of malignancy arise in a woman with endometriosis who desires pregnancy. PMID- 8200820 TI - Managed care: an opportunity for osteopathic physicians. AB - Managed care plans now enroll 38.6 million persons in the United States, and have increased their enrollment 14-fold in 5 years. The three major health reform proposals before Congress presently make managed care organizations, in one form or another, the linchpin of their reform plans. The authors trace the history of managed care leading to today's spectrum of plans from health maintenance organizations to preferred provider organizations with all their variants. They examine the government and insurance industry records of successes and failures and project the future for managed care with and without government-imposed healthcare reform. They unscramble the "alphabet soup" and detail the problems physicians have encountered in managed care settings. Given the key role of the primary care physician, the authors urge osteopathic physicians to take a proactive role in designing the shift to managed care. By supporting intelligent healthcare reform that brings physicians, hospitals, and insurers together in a practitioner-friendly system, the primary care physician can assume the leadership role in managed care and continue to serve as the patient advocate. PMID- 8200819 TI - Whiplash as a total-body injury. AB - In our highly active society, individuals and groups push their physical limits. Consequently, the incidence of whiplash injury is increasing. Patients may not recover rapidly or fully from a whiplash injury, thus leading to chronic neck and spinal symptoms and litigation. Physicians must recognize whiplash injury as a manifestation of total-body trauma and treat accordingly, with particular emphasis on alleviating abnormal tension of the fascia. Precise description of the accident, followed by healing methods tailored to well-defined bodily injury, aids in effective management. Whiplash injury poses a challenge to the osteopathic physician to sharpen skills in defining the injury based on the details of the accident and to incorporate myofascial release treatment into traditional modes of whiplash treatment. Fortunately, many highly respected osteopathic physicians have written extensively on the subject and the tools are at hand to refine treatment for both acute and chronic whiplash. PMID- 8200822 TI - Cigarette smoking still smolders after all these years. PMID- 8200823 TI - Revamp primary care programs to include psychiatry training. PMID- 8200824 TI - The incidence of the acquired immunodeficiency syndrome (AIDS) has peaked. PMID- 8200825 TI - Effects of adding sacral base leveling to osteopathic manipulative treatment of back pain: a pilot study. AB - A selected group of patients with sacral base unleveling greater than 2 mm were studied to determine the effects of osteopathic manipulative treatment (OMT) and heel lifting on chronic low-back pain. The McGill-Melzack Pain Questionnaire administered by trained personnel was used to assess the patient's pain before and after treatments. Five patients with no experience with manual treatment were treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and OMT for restrictions in spinal motion. Their improvement was statistically significant. Seven patients who had been treated previously with OMT and NSAIDs received heel lifts of graduated thickness until the sacral base was within 2 mm of being level. Attaining a "level" sacral base with heel lifts also provided a statistically significant relief from low-back pain. PMID- 8200826 TI - Adult nasolacrimal duct obstruction. AB - Tear production resulting from obstruction of the nasolacrimal duct is a common ophthalmic problem. The diagnosis and treatment of this condition require a thorough understanding of the lacrimal apparatus and its ocular and nasal relationships. Idiopathic or primary acquired nasolacrimal duct obstruction is a syndrome of unknown etiology. Of all nontraumatic forms, it accounts for the vast majority of cases found in adults. The authors discuss a number of potential causes, some of them iatrogenic and discuss the technique of dacryocystorhinostomy, the standard surgical treatment, in detail. PMID- 8200828 TI - Performance of candidates on the American Osteopathic Board of Internal Medicine subspecialty certifying examinations 1984-1992. AB - In 1973, the Board of Trustees of the American Osteopathic Association approved the Rules and Regulations of the American Osteopathic Board of Internal Medicine for the subspecialty certification program in internal medicine. The written objective examination process was finalized and implemented in 1984. Since 1984, 354 candidates have entered the examination process, with the largest number in the subspecialty field of cardiology. Through 1992, 91% of the candidates entering the examination process have passed the certifying examination and become certified. The number of first-time certifying-examination takers moderately increased in the last 2 years studied. The pass rate for first-time takers has averaged 75%, whereas the pass rate for repeaters has been 72%. PMID- 8200827 TI - Medicaid reform: an opportunity for the osteopathic medical profession. AB - Established in 1965 to provide medical care for the impoverished, the Medicaid program has pitted state governments against the federal government, and made adversaries of the providers. The authors examine the legislative history of the program and the rapid growth of expenditures that have led states to cut benefits, tighten eligibility requirements, and slash payments to providers. The call for comprehensive healthcare reform and universal access put Medicaid at the forefront of proposed changes. The osteopathic medical profession, which already provides a quarter of the care in the program, has an opportunity to lead in innovation to promote program efficiencies, and to affirm the profession's commitment to serve vulnerable populations. PMID- 8200829 TI - Telangiectasia macularis eruptiva perstans. AB - Telangiectasia macularis eruptiva perstans (TMEP) is a rare form of mastocytosis. It appears most frequently in adults and only occasionally will affect young children or infants. In this disease, multiple brownish-red confluent macules and telangiectasias develop, primarily on the trunk. Pruritus frequently occurs, and may be mild to severe. Most patients have only skin involvement; however, involvement may be systemic as well. Clinical signs and symptoms of systemic mastocytosis are varied and depend on which internal organs are affected. Classic symptoms--such as episodic flushing, gastrointestinal complaints, heart palpitations, and syncope--may be confused with those of other diseases, most notably the carcinoid syndrome. A simple workup can help to differentiate between these two conditions. The authors describe a 48-year old woman who was seen with cutaneous features of TMEP and with multiple symptoms suggesting systemic mastocytosis. They discuss the clinical features, diagnostic workup, and therapeutic options in the management of this relatively rare condition. PMID- 8200830 TI - Unusual manifestations of thoracic actinomycosis. AB - Actinomycosis is a chronic, suppurative bacterial infection characterized by multiple abscesses, sinus tracts, fibrosis, and granulation involving the face, neck, thorax, or abdomen. Thoracic actinomycosis probably results from aspiration of oropharyngeal secretions. Its description in the literature is extensive. Reported herein are two cases of thoracic actinomycosis with unusual manifestations exemplifying the organism's lack of regard for fascial planes. The authors present a comprehensive review of actinomycosis in order to encourage early diagnosis. The importance of bedside examination and inspection of available material stained by Gram's method are emphasized. Computed tomography scanning is a useful adjunct for assessing the anatomic extent of this disease. PMID- 8200831 TI - Higher education legislation and regulations: impact on accreditation. PMID- 8200832 TI - Critical challenges facing allied health accreditation: Pew Health Professions Commission's recommendations. PMID- 8200833 TI - Critical challenges facing allied health accreditation: pressures on higher education. PMID- 8200834 TI - Critical challenges facing allied health accreditation: pressures on accrediting bodies. PMID- 8200835 TI - Looking into the future of allied health: recommendations of the Pew Health Professions Commission. PMID- 8200836 TI - A futurist's view of health care and education: impact on specialized accreditation. PMID- 8200837 TI - The impact of higher education legislation and regulations on accreditation. PMID- 8200838 TI - The cost of accreditation to educational institutions. PMID- 8200839 TI - The cost of accreditation to accrediting bodies. PMID- 8200840 TI - Patient-centered outcome measures of accreditation. PMID- 8200841 TI - Application of technology to the accreditation process. PMID- 8200842 TI - Coordination issues in accreditation. PMID- 8200843 TI - Establishing an action agenda. PMID- 8200844 TI - Differentiation of a Ewing's sarcoma cell line towards neural and mesenchymal cell lineages. AB - Two different pathways of differentiation were investigated in Ewing's sarcoma (ES) cell line, designated CADO-ES1, which has been established in our laboratory. This cell line was induced to differentiate and display a neural phenotype when treated with dibutyryl cyclic adenosine monophosphate or when cultured in serum-free medium (HB101). In these in vitro differentiation studies, two different phenotypes were demonstrated by light and electron microscopy. One phenotype, present in a major portion of the cell population, had long neurites in which microtubules were ultrastructurally demonstrated. The other one, present in a minor portion of the cell population, consisted of flat cells with many short processes. After differentiation in serum-free medium, tumorigenicity in nude mice or colony-forming efficiency in soft agar was strongly depressed. In the cells, N-myc, c-fos and c-src genes were not amplified, and although c-myc was amplified by up to 2-fold, depending on the culture conditions, this appeared to be unrelated to the changes of phenotype. When tumor cells were transplanted into nude mice, cartilage was formed. The cartilage was immunoreactive with the antibody for HLA-ABC, indicating that it was derived from the tumor cells, not from mouse tissue. PMID- 8200845 TI - Incidence of second primary cancers in Osaka residents, Japan, with special reference to cumulative and relative risks. AB - This study was conducted to examine the incidence rates and cumulative risks of second primary cancers in Osaka and to compare the observed number of second primary cancers with the expected number calculated using cancer incidence rates among Osaka residents. Study subjects were all reported cases aged 0-79 who were first diagnosed as having a first primary cancer between 1966-86. Incidence of second primary cancer among the study subjects was examined through to the end of 1989. The total number of study subjects was 217,307. During the follow-up period (mean duration: 3.7 years), second primary cancers developed in 5,071 patients (2.3%). Incidence of synchronous (interval < 3 months) and metachronous (interval > or = 3 months) second primary cancers increased in the later years. Incidence rates of second primary cancers were significantly associated with gender (male), age and calendar year at diagnosis of the first cancer. Based on the incidence rates, cumulative risk of developing metachronous second primary cancer was calculated. The ten-year cumulative risk was estimated as 10% for those who developed their first cancer during their sixties in 1978-83. The observed number of second primary cancers (including synchronous) was compared with the expected number. The ratios of observed-to-expected numbers were generally lower than 1.0 among those who developed their first cancer in 1966-77, while these ratios were higher than 1.0 among those who developed their first cancer in 1978-86. The ratios were much higher than 1.0 among those who developed their first cancer in their childhood and youth. Patients who had developed cancer of the colon, larynx, lung, bladder, or breast (female) showed significantly higher risk of developing second primary cancer during the period 1-4 years after diagnosis of the first cancer. PMID- 8200846 TI - A case-control study on risk factors for uterine endometrial cancer in Japan. AB - A case-control study of 143 Japanese women with uterine endometrial cancer and 143 individually age-matched controls was conducted to assess the risk factors for endometrial cancers in Japan. Among the characteristics studied, the following factors were significantly greater in the cases than in the controls: nulliparity (odds ratio for parity 1-3 and > or = 4 versus nullipara are 0.40 and 0.02, respectively), obesity (odds ratio: 2.73), hypertension (odds ratio: 2.4), diabetes mellitus (odds ratio: 6.30), and a personal medical history of cancer (odds ratio: 3.06). The present study showed that Japanese women have the same risk factors for endometrial cancer as those reported in Western countries. The recent increase in the incidence of endometrial cancer in Japan may be largely attributed to the decrease in parity. PMID- 8200847 TI - Sequential decrease in tight junctions as revealed by 7H6 tight junction associated protein during rat hepatocarcinogenesis. AB - A sequential decrease in the number of hepatocyte tight junctions during the course of rat hepatocarcinogenesis was demonstrated by immunohistochemistry with a new 7H6 monoclonal antibody generated in our laboratory. Semiquantitative analysis by confocal laser scanning microscopy revealed that the expression of 7H6 antigen was reduced in hyperplastic foci, hyperplastic nodules and hepatocellular carcinomas (HCC) to 43%, 28% and 25%, respectively, compared to corresponding normal liver tissues. 7H6 antigen was scarce in HCC with a trabecular pattern, whereas it was expressed intensely at the apical and basolateral membrane of HCC with a glandular pattern. Immunoblot analysis of 7H6 expression in hepatocellular carcinomas showed a decrease roughly coincident with that shown by immunohistochemistry. These results indicated, for the first time, that tight junctions decrease progressively during carcinogenesis, leading to disruption of cellular polarity and cellular adhesiveness. PMID- 8200848 TI - Correlation between tumorigenicity and expression levels or splicing patterns of transcripts of the human papillomavirus type 16 E6 gene. AB - For determination of the correlation between tumorigenicity and the expression levels or splicing patterns of E6 mRNAs of the human papillomavirus type 16 in established cells, a vector containing the intact E6 open reading frame which expresses both unspliced and spliced mRNAs, one expressing only unspliced E6 mRNA, and one expressing both unspliced and spliced mRNAs but producing only truncated E6 proteins were constructed. In transformation assays and analyses of E6 mRNAs, a higher expression level of unspliced E6 mRNA was found to be closely associated with tumorigenicity. Furthermore, it was also related with anchorage independent growth and a decreased serum requirement of the cells. PMID- 8200850 TI - Identification and purification of a toxic component to B cell hybridoma cells in fetal calf serum. AB - A component exhibiting toxicity to B cell hybridoma cells was isolated and purified from fetal calf serum (FCS) by immunoaffinity chromatography using a monoclonal antibody (mAb) which reacted with the high-molecular-weight glycoprotein (6B3.Ag) recognized by a mAb, 6B3, to human large cell lung carcinoma cells (HLC-2). The component (FCS-6B3.Ag) was a high-molecular-weight antigen (approximately 1,000,000), consisting mainly of 76,000 subunits. FCS 6B3.Ag showed the same mobility in the pre-beta globulin region as that of 6B3.Ag on electrophoresis in 1.2% agarose gel. When FCS-6B3.Ag was analyzed by double immunodiffusion, it reacted with anti-6B3.Ag antiserum and the precipitin line fused partially with that formed between 6B3.Ag and anti-6B3.Ag antiserum. FCS 6B3.Ag was found to be toxic to hybridoma cells (anti-6B3.Ag, anti-alpha fetoprotein, anti-carcinoembryonic antigen or anti-C-reactive protein mAb producing cells) specifically in vitro at 5 micrograms/ml. The antigen also strongly suppressed their growth. The toxic effect of FCS-6B3.Ag appeared immediately after addition, and death of the target cells was complete only after 36-48 h. However, the antigen exhibited only weak suppression of Ig-non-secretory mouse myeloma (P3U1), thymic lymphoma (EL4) of mastocytoma (P815) cell growth. Five lots of FCS contained 2.1 to 4.1 micrograms/ml of FCS-6B3.Ag. PMID- 8200849 TI - Proto-oncogene expression in a human chondrosarcoma cell line: HCS-2/8. AB - HCS-2/8 is a stable human chondrosarcoma cell line with many chondrocytic characteristics and has the capacity to form chondrosarcomas in nude mice. The cells display both biochemically and morphologically definable changes in sparse, subconfluent, confluent and over-confluent phases of in vitro culture. Such features of HCS-2/8 cells may reflect the processes of both proliferation and differentiation of chondrocytes in vivo. We examined the correlations of these changes of HCS-2/8 cells with their transcript levels of 21 proto-oncogenes by Northern analysis. We found no detectable transcripts of 9 proto-oncogenes (c sis, c-met, c-src, c-lyn, c-fgr, c-ros, c-pim, Blym and N-myc), but detected transcripts of 12 other proto-oncogenes (int-2, erbB, c-abl, c-raf-1, c-fyn, K ras, H-ras, c-mos, c-myc, c-myb, c-fos, and c-jun). In the over-confluent phase, the levels of c-fos and c-raf-1 were increased several dozen times and about 5 times, respectively, while the level of c-abl was about 1/5th of that in the sparse, subconfluent and confluent phases of culture. The level of int-2 increased about 10-fold in the confluent and over-confluent phases of in vitro culture. The transcript levels of c-mos and K-ras were high in the sparse phase, low in the subconfluent and confluent phases and high in the over-confluent phase. The levels of the other 6 proto-oncogenes in HCS-2/8 cells were constant in all phases of in vitro culture. PMID- 8200851 TI - Modulation of growth factor receptors on acute myeloblastic leukemia cells by retinoic acid. AB - The effects of retinoic acid (RA) on the proliferation of acute myeloblastic leukemia (AML) cells were studied. AML samples were divided into three groups. Namely, RA stimulated blast colony formation by AML samples in group A and inhibited that by the samples in group B, regardless of added growth factors. For the samples in group C, RA inhibited the colonies formed by granulocyte colony stimulating factor (G-CSF) but stimulated those by granulocyte macrophage CSF (GM CSF). To investigate the mechanism involved, the effects of RA on growth factor receptors on AML cells were examined by flow cytometry using fluorolabeled ligands. For the samples in groups A and B, RA affected neither G-CSF receptor (GR) nor GM-CSF receptor (GMR). For the samples in group C, exposure to 10(-7) M RA for 1 day clearly increased GMR, but did not affect GR. This finding supports the hypothesis that the increase of GMR is one of the causes of the stimulative effects of RA on cells cultured with GM-CSF in group C. PMID- 8200852 TI - Lethal midline granuloma in Okinawa with special emphasis on polymorphic reticulosis. AB - Lethal midline granuloma (LMG) is a clinical term used to describe a condition which may be manifested histologically as Wegener's granulomatosis (WG), polymorphic reticulosis (PR), and malignant lymphoma (ML). WG is an inflammatory disease, and PR and ML are considered to represent a neoplastic proliferation of lymphoreticular cells. In this report, twenty-two cases of LMG in Okinawa were examined. The frequency of LMG per 100,000 outpatients of the ear, nose and throat clinic in Okinawa was 67, and the higher frequency of PR (27) and ML (34) in Okinawa than in other districts of Japan was characteristic. Polymerase chain reaction, in situ hybridization, and immunohistochemical studies showed that the proliferating cells in PR were CD43+ and simultaneously contained Epstein-Barr viral genome in their nuclei. The higher frequency of PR and ML in Okinawa is discussed in conjunction with a review of pertinent literature: multiple factors including genetic, viral environmental, and socioeconomic factors seem to affect the frequencies of these diseases. PMID- 8200853 TI - A novel antitumor antibiotic, KW-2189 is activated by carboxyl esterase and induces DNA strand breaks in human small cell lung cancer cells. AB - KW-2189 has been selected as a lead compound for clinical trial among duocarmycin derivatives with structural similarity to CC-1065, a cyclopropylpyrroloindole. The purpose of this study was to examine the DNA-binding potency and the mechanisms of cytotoxicity of KW-2189. In order to analyze DNA-binding activity of KW-2189, plasmid pBR322 was treated with KW-2189 with or without pretreatment with carboxyl esterase, which we demonstrated to be an activating enzyme, and the products were examined by agarose gel electrophoresis and restriction enzyme analysis. Cytotoxic activity was examined by exposing a human small cell lung cancer cell line, NCI-H69 to KW-2189 with or without carboxyl esterase. Alkaline elution was performed to examine whether KW-2189 induces DNA strand breaks. DNA treated with KW-2189 and carboxyl esterase migrated faster than KW-2189-treated DNA, which migrated at the same rate as untreated DNA. In addition DNA treated with esterase-activated KW-2189 was protected from digestion by some restriction enzymes. KW-2189 showed concentration- and time-dependent growth inhibitory effect with IC50 values (drug concentration required for 50% growth inhibition) of 58 nM (96 h) to 1900 nM (1 h) in H69 cells. The IC50 values of 4-h exposure of H69 to KW-2189 with 0, 26, 130, 650 mU/ml carboxyl esterase were 460, 120, 30, and 7 nM, respectively. Time-dependent enhancement of cytotoxicity by carboxyl esterase was also observed. KW-2189 induced DNA strand breaks in H69 cells in a concentration-dependent manner around the IC50 value. We conclude that 1) KW-2189 is activated by carboxyl esterase to its active form(s), 2) activated KW-2189 has a stronger DNA-binding activity and cytotoxicity than KW-2189, 3) DNA cleavage is one of the major mechanisms of KW-2189-mediated cytotoxicity. PMID- 8200854 TI - Active efflux system for cisplatin in cisplatin-resistant human KB cells. AB - Mutants, KCP-4 and PC-5, resistant to an anticancer agent, cisplatin, were selected in multiple steps from human epidermoid KB carcinoma cells and human prostate PC-3 carcinoma cells, respectively. KCP-4 and PC-5 were 63 and 10 fold more resistant to cisplatin than the parental cells, respectively. KCP-4 cells exhibited increased resistance to cisplatin analogues and were also slightly cross-resistant to melphalan, cyclophosphamide, mitomycin C and methotrexate. KCP 4 cells were not cross-resistant to doxorubicin, daunorubicin, vincristine or CdSO4. The accumulations of cisplatin in KCP-4 cells and PC-5 in medium containing 50 microM cisplatin were approximately 20% of those in the parental cells. Revertant analysis suggested that a defect in cisplatin accumulation may be related to cisplatin resistance in PC-5 cells. The uncoupling agent of oxidative phosphorylation, 2,4-dinitrophenol, increased the accumulation of cisplatin in KCP-4 and cisplatin-resistant human prostate carcinoma PC-5 cells to nearly the same level as in their parental KB-3-1 and human prostate carcinoma PC 3 cells without 2,4-dinitrophenol, but did not increase accumulation in KB-3-1 and PC-3 cells. Addition of glucose in the medium inhibited the enhancement of cisplatin accumulation in KCP-4 cells by 2,4-dinitrophenol. Enhanced active efflux of cisplatin from KCP-4 cells was observed. A cell-cell hybridization test showed that the cisplatin resistance and the accumulation defect behaved as codominant traits. These data suggest that an active efflux system for cisplatin exists in cisplatin-resistant KCP-4 cells. PMID- 8200855 TI - Improvement of therapeutic effect by using Fab' fragment in the treatment of carcinoembryonic antigen-positive human solid tumors with adriamycin-entrapped immunoliposomes. AB - To improve the therapeutic efficiency adriamycin entrapped in antibody-conjugated liposomes, Fab' fragment was used instead of the whole antibody molecule. The murine monoclonal antibody, 21B2, against human carcinoembryonic antigen (CEA) was digested with pepsin, and the thiol residue of intra-heavy chain produced by reduction of F(ab')2 with dithiothreitol was conjugated to liposomes containing adriamycin. The tissue distribution of adriamycin delivered with these liposomes was studied in BALB/c nu/nu female mice bearing CEA-positive human gastric cancer strain MKN-45. An increase in delivery of adriamycin to the tumor was observed in the mice given liposomes with Fab' fragment as compared to those given liposomes with whole antibody. However, the preferential distribution of adriamycin in liposomes to the reticuloendothelial cells remained the same regardless of the use of Fab' fragment. For investigation of in vivo therapeutic effect, three i.v. injections of free adriamycin or adriamycin in liposomes equivalent to 5 mg/kg were given, and adriamycin in Fab' fragment-conjugated liposomes was found most effective in the inhibition of tumor growth. This was confirmed in terms of actual tumor weights excised and CEA concentration in the blood, as well as by pathological observations. The advantages of using Fab' fragment instead of whole antibody are discussed. PMID- 8200856 TI - Characterization of larvicidal toxin protein from Bacillus thuringiensis serovar japonensis strain Buibui specific for scarabaeid beetles. AB - The delta-endo toxin proteins from Bacillus thuringiensis which kill the larvae of various scarabaeid beetles such as Anomala cuprea, A. rufocuprea and Popillia japonica were purified by DEAE ion exchange chromatography. A protein with a molecular size of 130 kDa was purified. During the purification a minor peak was also detected which was estimated to be 67 kDa by SDS-PAGE. Both 130 and 67 kDa proteins showed larvicidal activity against A. cuprea. The lethal concentration of the 130 kDa protein which killed 50% of the larvae tested (LC50) against A. cuprea was 2 micrograms g-1 compost. A comparison by SDS-PAGE of the V8 protease digestion pattern of the 130 and 67 kDa larvicidal proteins showed that proteolytic resistant core peptides of approximately 60 kDa molecular size were resulted. The N-terminus amino acid sequence of the 130 and 67 kDa proteins was determined to be NH2-XXPNNQNEYEIIDAL and NH2-XSRNPGTFI, respectively, which is not identical to the sequence of CryIA, CryIB, CryIC and CryIII proteins. PMID- 8200857 TI - A variable response of degrading bacteria to phosphorus added to natural water. AB - The effect of inorganic phosphorus (P) on the degradation of 10 mg l-1 of para nitrophenol (PNP) or 2,4-dichlorophenoxyacetic acid (2,4-D) by three test bacteria inoculated into Nile water samples was investigated. The response of the organisms to P depended mainly on their affinity for the available P. Thus, Corynebacterium sp. at an initial density of 3.3 x 10(4) cells ml-1 readily degraded 10 mg l-1 of PNP in filter-sterilized Nile water supplemented with 22.8 mg l-1 of P. The same effect was observed when Pseudomonas cepacia was inoculated into Nile water amended with PNP and supplemented with 2.28-22.8 mg l-1 of P. The bacteria grew in Nile water and the final densities were related to the level of the added P. On the other hand, the addition of P, at concentrations ranging from 2.28 to 22.8 mg l-1, to sterile Nile water inoculated with Pseudomonas sp. and amended with 10 mg l-1 of 2,4-D did not stimulate the degradation compared with that obtained with the unsupplemented samples. The affinity of the three strains to P was demonstrated in P-deficient medium amended with PNP or 2,4-D as a sole carbon source. The pH of the medium was adjusted with 0.1 mol l-1 Tris buffer. Pseudomonas sp. at an initial density of 3.3 x 10(4) cells ml-1 degraded 10 mg l 1 of 2,4-D in non-sterile Nile water without added P. A slight enhancement of degradation was observed in water samples amended with a high concentration of P.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200858 TI - Tetracycline resistance genes in staphylococci from the skin of pigs. AB - Forty-seven tetracycline-resistant staphylococci from the skin of pigs were examined for genes mediating this resistance. Seventeen isolates were also resistant to minocycline and all hybridized with the tet(M) gene; 23 carried the tet(K) gene and 10 the tet(L) gene. Three carried more than one gene and two did not hybridize with any of the three probes tested. Maps were constructed for two plasmids carrying the tet(K) gene, all were very similar in size (4.35-4.7 kb) and structure and closely resembled the plasmid pT181. Four plasmids which bore the tet(L) gene differed in size, ranging from 4.3 to 11.5 kb, and were dissimilar in structure except for the portion bearing the gene. PMID- 8200859 TI - Multilocus enzyme electrophoresis on agarose gel as an aid to the identification of entomopathogenic Bacillus sphaericus strains. AB - Sixty strains of Bacillus sphaericus, including 31 insect pathogens were studied by multilocus enzyme electrophoresis and were classified into 44 zymovars (electrophoretic types). Among the entomopathogenic strains, 11 belong to the same zymovar (Z59) indicating a widespread frequent genotype. Bands of enzyme activity were not detected among the strains for the loci GPI (E.C.5.3.1.9), G6P (E.C.1.1.1.49), 6PG (E.C.1.1.1.44) and ME (E.C.1.1.1.40). The enzymatic loci NP (E.C.2.4.2.1) and ACON (E.C.4.2.1.3) were monomorphic while the other enzymes, MDH (E.C.1.1.1.37), LeDH (E.C.1.4.1.9), ADH (E.C.1.4.1.1), EST (E.C.3.1.1.1), PEP 2 (E.C.3.4.11.1), PEP-3 (E.C.3.4.11) and PEP-D (E.C. 3.4.13.9) were polymorphic. The genetic variation in the non-insect pathogenic group seemed to be greater than in the entomopathogenic group. This latter group appears to be distinct from other strains of these species. All insect pathogens were recovered in the same phenetic cluster and a diagnostic allele is reported for the identification of entomopathogenic strains. PMID- 8200860 TI - Assessment of the marker value of various components of the coli-aerogenes group of Enterobacteriaceae and of a selection of Enterococcus spp. for the official monitoring of drinking water supplies. AB - The traditional indicators Escherichia coli (in practice currently, though ecologically inaccurately, represented by 'thermotolerant coliforms' at 44 degrees C) and Enterococcus spp. proved to be suitable for the diagnosis of heavy and frequent faecal pollution observed in potentially dangerous waters, especially those originating from karstic aquifers. On the other hand, natural and treated waters, slightly and inconsistently contaminated, occasionally showed a variable Gram-negative flora, difficult to classify by routine tests. In that case, complete identification of isolates may be necessary to ensure a valid decision on the potability of the supply. At any rate some of the Enterobacteriaceae contained in the 'faecal coliform' group and many other 'coliforms', distinct from E. coli, lack sanitary significance although their presence at certain levels may indicate inadequate disinfection, hiatuses in the integrity of the distribution system or both. PMID- 8200861 TI - Survival of Salmonella senftenberg and Salmonella typhimurium in glassy and rubbery states of gelatin. AB - Salmonella senftenberg and Salmonella typhimurium survived the production of gelatin sheets containing nutrient broth although there was some evidence of cell damage. Both strains survived but did not grow in glassy states with an a(w) of 0.45-0.28 and rubbery states with an a(w) of 0.93-0.96 for at least 28 d. Survival was less in intermediate states with an a(w) between 0.55 and 0.74. The results suggest that salmonellas should be excluded from glassy state products in order to prevent salmonellosis. PMID- 8200862 TI - Vitamin and amino acid requirements of Lactobacillus plantarum strains isolated from green olive fermentations. AB - The requirement for essential amino acids and vitamins was determined in wild type Lactobacillus plantarum strains isolated from green olive fermentation brines. All the strains were found to be auxotrophic with respect to the amino acids but some of them were prototrophic for pyridoxal, p-aminobenzoic acid and/or nicotinic acid. Their growth response to these nutrients was also studied and found to be quite heterogeneous. Nutritional requirement pattern as a criteria for selecting starter cultures is discussed. PMID- 8200863 TI - Thermal resistance of partially purified proteinase of Pseudomonas fluorescens P 26. AB - Heat resistance of the Pseudomonas fluorescens P-26 proteinase in terms of D value was studied in whole milk, skim milk, whey and 0.05 mol l-1 phosphate buffer at 72.5, 130, 135, 140, 145 and 150 degrees C subsequent to its partial purification through (NH4)2 SO4 precipitation (45-65% saturation) and solvent fractionation with 1.0 to 2.0 volumes of isopropanol. The D-value was maximum for the proteinase at all temperatures when determined in whole milk (D150 = 0.088). PMID- 8200864 TI - Chitinolytic properties of Bacillus pabuli K1. AB - The chitinolytic properties of Bacillus pabuli K1 isolated from mouldy grain was studied. Chitinase activity was measured as the release of p-nitrophenol from p nitrophenyl-N,N'-diacetylchitobiose. Influences of substrate concentration and different environmental variables on growth and chitinase activity were determined. The optimum environmental conditions for chitinase production were: 30 degrees C, initial pH 8, initial oxygen 10% and aw > 0.99. Chitinase production was induced when B. pabuli K1 was grown on colloidal chitin. The smallest chito-oligosaccharide able to induce chitinase production was N,N' diacetylchitobiose, (GlcNAc)2. Production was also induced by (GlcNAc)3 and (GlcNAc)4. When the bacterium was grown on glucose or N-acetylglucosamine, no chitinases were formed. The highest chitinase production observed was obtained with colloidal chitin as substrate. The production of chitinases by B. pabuli K1 growing on chitin was repressed by high levels (0.6%) of glucose. The production was also repressed by 0.6% starch, laminarin and beta-glucan from barley and by glycerol. The addition of pectin and carboxymethyl cellulose increased chitinase production. PMID- 8200865 TI - Effect of substrate on the production of antifungal volatiles from Bacillus subtilis. AB - An antibiotic-producing strain of Bacillus subtilis has been shown to produce potent antifungal volatiles (AFV). These volatiles are active against a range of fungal species and are produced on a range of growth media and in loam-based compost. In vitro antifungal volatile activity on nutrient agar is enhanced with the addition of D-glucose, complex carbohydrates and peptones. The addition of L glucose led to significantly less AFV activity than comparable levels of D glucose. Growth studies in liquid culture revealed that B. subtilis failed to grow in response to L-glucose. Further growth studies on solid media showed no clear correlation between enhanced bacterial growth and increases in in vitro AFV activity in response to supply of substrates. Low level AFV activity was also detected from oilseed rape roots inoculated with B. subtilis. Gas chromatography mass spectrometry headspace analysis of B. subtilis cultures grown on various substrates revealed common similarities between substrates promoting AFV activity, although it was not possible to isolate individual antifungal compounds. PMID- 8200866 TI - Fermentation of fructans by epiphytic lactic acid bacteria. AB - A total of 712 strains of lactic acid bacteria isolated from forage grasses were studied for their ability to ferment fructans of phlein- as well as inulin-type. Only 16 strains utilized phlein and eight of these also fermented inulin. They were identified as Lactobacillus paracasei subsp. paracasei, Lact. plantarum, Lact. brevis and Pediococcus pentosaceus. In the species Lact. paracasei subsp. paracasei, all strains gave positive results, whereas the other positive strains possessed unique properties within their own species. In all but two cases (strains of the species Lact. plantarum), the phlein was more intensively fermented than the inulin, as indicated by a lower pH and a higher lactic acid concentration. On the basis of the outcome of this study it seems worthwhile to inoculate grasses of low sugar content before ensiling with an active strain that can ferment fructans. PMID- 8200867 TI - The effect of electron beam irradiation and modified pH on the survival and recovery of Escherichia coli. AB - The severity of radiation processing can be reduced by combining irradiation with other treatments, such as low pH. An exponential phase culture of Escherichia coli was irradiated at doses of 0-2.4 kGy at pH values ranging between 7.0 and 4.0, in an enriched nutrient broth. At pH 4.3 and above there was no significant effect of lowering the pH prior to irradiation. At pH 4.13 and 4.0, a much higher level of cell death occurred compared with irradiation at pH 7.0. This synergistic effect was observed only when the pH was lowered before radiation processing. PMID- 8200868 TI - Distorting children's reports and interpretations of events through suggestion. AB - Fifty-four children (33 girls and 21 boys), 4 to 6 years old, participated in an experiment examining the effects of leading interviews on their interpretations and factual recall of an interaction with a teaching assistant (TA). Children were either familiar or unfamiliar with the TA and were interviewed in either an incriminating or a neutral manner. In comparison with neutral-interview children, incriminating-interview children made more cued-recall errors and endorsed more biased interpretations of the TA's actions. Familiarity with the TA had limited effects on free recall and interpretations of the TA's actions and had no effect on cued recall. Results indicated that 4- to 6-year-olds will produce misleading reports about their interactions with either familiar or unfamiliar adults when they are prompted to do by an opinionated adult interviewer. PMID- 8200869 TI - Using mug shots to find suspects. AB - The authors examined the use of mug shots as an investigative tool. Data are reported from 3 staged-crime experiments (N = 365) exploring the effects on mug shot selections of number of faces seen before the confederate criminal's, of biased procedures, and of sorting pictures to fit the description of the criminal. The confederate was frequently selected from mug shots, and few innocent people were selected. Selections of faces declined with number of pictures viewed before the confederate's. Biased instructions and clothing bias increased choices of innocent people but not of guilty people. More innocent faces were selected when the pictures matched the confederate's description than when the pictures were not sorted to match the confederate's description. Viewing mug shots had no effect on subsequent identifications in lineups. Implications for police use of mug shots are discussed. PMID- 8200870 TI - Adolescent life experiences as predictors of occupational attainment. AB - Adolescent life experiences, measured with Owen's Biographical Questionnaire (BQ), were used to predict occupational attainment 16 years to 21 years later in a sample of 1,523 college graduates. Study participants completed the BQ in either 1968 or 1970-1973 as college freshmen and subsequently reported their occupational status in 1989. Jobs were rationally clustered into 18 different categories. Separate gender analyses were conducted in which 13 BQ factors were used as predictors of occupational attainment. Effect sizes were substantially larger than those obtained in an earlier study by A. G. Neiner and W. A. Owens (1985). The usefulness of life experience data for understanding occupational choices as well as implications for college counseling are discussed. PMID- 8200871 TI - Genetic and environmental influences on perceptions of organizational climate. AB - Genetic and environmental influences on perceptions of organizational climate were assessed by using a 4-group twin design. Data were obtained as part of the Swedish Adoption/Twin Study of Aging. The Work Environment Scale (WES) was used to evaluate perceptions of organizational climate. A measure of job satisfaction was also used to evaluate the effects of genes and environments on job attitudes. Maximum likelihood estimates of genetic and environmental influence suggested significant genetic effects for Supportive Climate--1 factor resulting from a factor analysis of the WES--but not for a second factor, Time Pressure. Significant environmental effects were found for both Supportive Climate and Time Pressure. Genetic effects were not significant for job satisfaction. The relevance of findings to organizational climate research and personnel selection are discussed. PMID- 8200872 TI - Investigation of perceived environment, perceived outcome, and person variables in relationship to voluntary development activity by employees. AB - The authors examined perceived environment, perceived incentive and outcome, and person constructs for relationships with interest and participation in voluntary learning and development activity by nonmanagement employees. All 3 groups of constructs were related to development activity. In relationships with development activity, perceived outcome and environment variables interacted with workers' personal values relevant to aspects of a development setting, illustrating the potentially important role that differences in values may play in a development setting, illustrating the potentially important role that differences in values may play in a development context. Additionally, small relationships were observed between several demographic variables and values within a development setting. Results provide implications for the design and implementation of successful development programs and highlight the need to carefully consider individual differences in this context when targeting many different types of employees for participation. PMID- 8200873 TI - Effects of work task cues and play task cues on information processing, judgment, and motivation. AB - How task cues affect cognition, attitudes, and behavior was explored in this laboratory study with 82 master of business administration students. Linguistic analysis of responses to the same puzzle task, cued as either work or play, revealed that task cues influenced how information was perceived and was used to form judgments and to shape behavioral responses. Ss performing work tasks attended more to information about the quantity of their performance and made more streamlined, goal-directed responses. Ss performing play tasks attended more to information about the quality of their performance; made more elaborated, image-laden responses; and were more intrinsically motivated. Links among task cues, cognitive processes, and performance were explicated through path analysis. Task cues affected performance outcomes indirectly by instantiating associated cognitive orientations: a means orientation in play and an ends orientation in work. PMID- 8200874 TI - Does the medium matter? The interaction of task type and technology on group performance and member reactions. AB - The authors investigated the hypothesis that as group tasks pose greater requirements for member interdependence, communication media that transmit more social context cues will foster group performance and satisfaction. Seventy-two 3 person groups of undergraduate students worked in either computer-mediated or face-to-face meetings on 3 tasks with increasing levels of interdependence: an idea-generation task, an intellective task, and a judgment task. Results showed few differences between computer-mediated and face-to-face groups in the quality of the work completed but large differences in productivity favoring face-to-face groups. Analysis of productivity and of members' reactions supported the predicted interaction of tasks and media, with greater discrepancies between media conditions for tasks requiring higher levels of coordination. Results are discussed in terms of the implications of using computer-mediated communications systems for group work. PMID- 8200875 TI - Postpartum amenorrhoea and breast-feeding in a Danish sample. AB - The duration of postpartum amenorrhoea was studied in a Danish sample of 361 women. The median duration of amenorrhoea was 17 weeks. The 25th and 75th percentiles were 10 and 30 weeks, respectively. A significant correlation was found between the duration of postpartum amenorrhoea and of breast-feeding. However, lactation for more than 9 months did not extend the duration of amenorrhoea. Menstruation before weaning occurred in 57% of the women, and 43% terminated breast-feeding before the first menstruation. Four weeks after weaning menstruation had returned in 79% and by 8 weeks after in 93% of the mothers. At 6 months postpartum, frequency of breast-feeding, and of night-time feeding were determinants of amenorrhoea. PMID- 8200876 TI - Trends in fertility and intermarriage among immigrant populations in Western Europe as measures of integration. AB - Demographic data on fertility and intermarriage are useful measures of integration and assimilation. This paper reviews trends in total fertility and intermarriage of foreign populations in Europe and compares them with the trends in fertility of the host population and the sending country. In almost all cases fertility has declined. The fertility of most European immigrant populations and of some West Indian and non-Muslim Asian populations has declined to a period level at or below that of the host society. Muslim populations from Turkey, North Africa and South Asia have shown the least decline. Intermarriage is proceeding faster than might be expected in immigrant populations which seemed in economic terms to be imperfectly integrated. Up to 40% of West Indians born in the UK, for example, appear to have white partners as do high proportions of young Maghrebians in France. PMID- 8200877 TI - The effect of price increases on contraceptive sales in Bangladesh. AB - In April 1990, the prices of five brands of contraceptives in the Bangladesh social marketing project were increased, by an average of 60%. The impact on condom sales was immediate and severe, with sales for the following 12 months dropping by 46% from the average during the preceding 12 months. The effect on oral contraceptive sales was less dramatic: average sales in the year following the increases dropped slightly despite a previously established pattern of rapidly rising sales. There appears no reasonable combination of events other than the price increase itself to explain most of the difference. PMID- 8200878 TI - Gender-related differences in the impact of tropical diseases on women: what do we know? AB - This paper explores the importance of gender differences in the impact of tropical diseases on women. Malaria and schistosomiasis are used as examples but most of the observations also apply to other diseases endemic to developing countries. The distinction between sex and gender is discussed and evidence of sex and gender differences in the determinants and consequences of malaria and schistosomiasis, particularly their economic, social and personal dimensions, is reviewed. Issues on which research and intervention studies are needed are identified. PMID- 8200879 TI - Determinants of racial fertility differentials in some urban areas of South Africa. AB - Results of a survey of some urban areas in the Pretoria-Witwatersrand-Vereenining region show differential impacts of proximate and socioeconomic factors on the fertility of urban blacks and whites. Timing of starting and ending of childbearing and the reproductive behaviour of women who have never been married account for the major differences in fertility levels. White women confine their childbearing career to the 20-39 age range, while black women utilise the entire 15-49 age range. The fertility level is quite high among black women who have never been married (in contrast to never married white women). With the exception of breast-feeding, racial patterns in other proximate determinants of fertility do not suggest the observed racial differentials in fertility. PMID- 8200880 TI - The intelligence of American children is still rising. AB - Children's intelligence increased in the United States by approximately 3 IQ points per decade over the period 1932-78. New evidence shows that these increases have been sustained during the last 20 years. Two recent studies indicate that the rates of increase for 1972-89 and 1978-89 were 3.3 and 3.5 IQ points per decade, respectively. PMID- 8200881 TI - Comparison of effects of breast-feeding practices on birth-spacing in three societies: nomadic Turkana, Gainj, and Quechua. AB - Variation in the duration and pattern of breast-feeding contributes significantly to inter-population differences in fertility. In this paper, measures of suckling frequency and intensity are used to compare the effects of breast-feeding practices on the duration of lactational amenorrhoea, and on the length of the birth interval in three prospective studies undertaken during the 1980s, among Quechua Indians of Peru, Turkana nomads of Kenya, and Gainj of Papua New Guinea. In all three societies, lactation is prolonged well into the second year postpartum, and frequent, on-demand breast-feeding is the norm. However, the duration of lactational amenorrhoea and the length of birth intervals vary considerably. Breast-feeding patterns among Gainj and Turkana are similar, but Turkana women resume menses some 3 months earlier than do the Gainj. The average birth interval among the Gainj exceeds that of nomadic Turkana by over 15 months. Suckling activity decreases significantly with increasing age of nurslings among both Gainj and Quechua, but not among Turkana. Earlier resumption of menses among Turkana women may be linked to the unpredictable demands of the pastoral system, which increase day-to-day variation in the number of periods of on-demand breast feeding, although not in suckling patterns. This effect is independent of the age of infants. The short birth intervals of Turkana women, relative to those of the Gainj, may be related to early supplementation of Turkana nurslings with butterfat and animals' milk, which reduces energetic demands on lactating women at risk of negative energy balance. PMID- 8200882 TI - Isonymy and the genetic structure of Sicily. AB - The genetic structure of Sicily was analysed through the distribution of surnames of 758,793 users registered in the Italian Telephone Company, corresponding to 371 communes of the island. Estimates of the coefficient of consanguinity due to random isonymy, of Fisher's a, an indicator of abundance of surnames, and of Karlin-McGregor's v, an indicator of immigration rates, were obtained for each commune. Four different estimates of genetic distance between all possible pairs of communes within each province were also obtained, and their relationship with geographic distance was studied. The logarithmic transformation of Lasker's coefficient of relationship showed correlations with the log of geographic distance which range between -0.78 and -0.40; the strongest, for the province of Catania, was attributed to the presence of Mount Etna, and the weakest, for Palermo, to the high population density of this province. PMID- 8200883 TI - Consanguineous marriage within social/occupational class boundaries in Pakistan. AB - Data on patterns of consanguineous marriage were collected from 5340 families resident in eight cities in the Pakistan province of Punjab. To assess whether social and/or occupational class was interacting with consanguinity, information also was obtained on the hereditary qaum to which each family belonged. In the present generation 46.5% of all marriages were contracted at the level of second cousin or closer, with an average coefficient of inbreeding (F) of 0.0286, and the results indicated that in each of the seventeen qaums there was strong preference for marriage to a close biological relative. However, significant differences existed in the distribution of consanguineous marriage by qaum membership, which could interfere with the interpretation of studies into the biological effects of inbreeding. PMID- 8200884 TI - Aspects of neonatal death in St Kilda, 1830-1930. AB - Neonatal death (mainly due to tetanus) was common in St Kilda until 1891. Two aspects of this phenomenon are studied; factors which predicted death, and the impact of neonatal death on family building. Maternal age appeared to be a predictive factor for death of the first child, but only in children of high birth order were other factors, particularly the number of previous neonatal deaths, important. The first birth interval appeared to be determined mainly by the date of the first birth, independent of neonatal mortality levels. For later intervals, the neonatal death of the previous child appeared to be the main determining factor. PMID- 8200885 TI - Cost containment: total joint implants. PMID- 8200886 TI - The hospital cost and the cost of the implant for total knee arthroplasty. A comparison between 1983 and 1991 for one hospital. AB - The hospital cost of total knee arthroplasty at the Lahey Clinic was evaluated by a comparison of the data for twenty-eight patients who had had the operation in 1983 with the data for forty-two patients who had had the same operation in 1991. The hospital bills were analyzed for each patient. Each hospital charge was converted to cost with the use of government-mandated hospital-specific cost-to charge ratios. The average actual hospital cost for total knee arthroplasty increased 17 per cent, from $10,122 in 1983 to $11,826 in 1991. However, in inflation-adjusted dollars, the hospital cost for total knee arthroplasty decreased 15 per cent during this period. When the costs for total knee arthroplasty in 1983 and 1991 were allocated to various service centers in the hospital, the cost for a hospital room was found to have decreased from 47 per cent of the hospital cost in 1983 to 31 per cent of that in 1991. The cost of a hospital room decreased 23 per cent in actual dollars and 46 per cent in inflation-adjusted dollars during this period. In sharp contrast, the cost of a knee implant increased from 13 per cent of the hospital cost for total knee arthroplasty in 1983 to 25 per cent of that in 1991. The average cost of the prosthesis increased from $1359 in 1983 to $2960 in 1991. This represents a 118 per cent increase in actual dollars. The inflation-adjusted increase in the cost of the implant was 59 per cent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200887 TI - Synovectomy of the ankle for hemophilic arthropathy. AB - The results of five patients who had hemophilia and a history of recurrent hemarthrosis and hypertrophic synovitis and who had been managed with a synovectomy of the ankle were studied at an average age of nine years (range, four years and seven months to nineteen years). Compared with the complications encountered after synovectomy of the knee or the elbow, the rehabilitation process after synovectomy of the ankle was relatively easy, even for the three youngest children in this series. The average duration of follow-up was five years (range, one to nine years). By the latest follow-up examination, the range of motion of the ankle had increased an average of 10 degrees (range, -5 to 15 degrees). The rate of hemarthrosis episodes requiring transfusion was reduced from an average of 3.4 per month (range, 0.3 to 5.0 per month) for the six months before the synovectomy to 0.1 per month (range, zero to 0.2 per month) for the twelve months before the latest follow-up examination. PMID- 8200888 TI - A prospective, double-blind trial of electrical capacitive coupling in the treatment of non-union of long bones. AB - Twenty-three patients who had an established non-union of a long bone were entered into a prospective, double-blind trial in which electrical capacitive coupling was used for treatment. Twenty-one patients completed the study: ten who were actively managed and eleven who were managed with a placebo unit. The non union healed in six of the ten patients who had been managed actively but in none of the patients who had been managed with the placebo unit. This difference in the rates of healing between the actively managed and the placebo groups is highly significant (p = 0.004). PMID- 8200890 TI - A biomechanical analysis of prophylactic fixation for pathological fractures of the distal third of the humerus. AB - Twenty-four matched pairs of fresh-frozen humeri from human cadavera were divided randomly into four groups, in order to determine the most biomechanically desirable construct for the prophylactic fixation of impending fractures of the distal third of the humerus. Group I comprised intact humeri and matched humeri in which a 50 per cent lateral, semicylindrical cortical defect of the distal third had been created, resulting in a reproducible model of an impending fracture due to a lytic defect involving 50 per cent cortical disruption at the distal end of the humeral medullary canal. In Group II, such a lateral defect was created in both the right and the left, matched humeri. Group III was composed of humeri in which the defect had been fixed prophylactically with a single plate and the contralateral humeri, which had been treated with double-plating. Group IV comprised specimens in which the defect had been fixed with double-plating as well as those fixed with Rush rods. The fixation of each specimen in Groups III and IV was supplemented with bone cement. Each specimen was tested in torsion to failure, and the resulting peak torque, torsional stiffness, and total energy absorbed were analyzed for each group. The Group-I specimens that had a defect had a significantly lower (p < 0.05) peak torque, torsional stiffness, and total energy absorbed than the intact specimens; all of the specimens with a defect failed at the defect, and all of the intact specimens failed proximally. In Group II, there was a high side-to-side association with respect to peak torque, torsional stiffness, and total energy absorbed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200889 TI - The effect of recombinant human osteogenic protein-1 on healing of large segmental bone defects. AB - A rabbit ulnar non-union model was used to evaluate the effect of recombinant human osteogenic protein-1 on the healing of a large segmental osteoperiosteal defect. A 1.5-centimeter segmental defect was created in the mid-part of the ulnar shaft of adult rabbits. The defect was filled with an implant containing either recombinant human osteogenic protein-1 or naturally occurring bovine osteogenic protein. The recombinant human osteogenic protein-1 implants consisted of a carrier of 125 milligrams of demineralized, guanidine-extracted, insoluble rabbit bone matrix (the collagen carrier), reconstituted with 3.13, 6.25, 12.5, twenty-five, fifty, 100, 200, 300, or 400 micrograms of recombinant human osteogenic protein-1. Animals that received recombinant human osteogenic protein 1 were compared with animals that received an implant of 250 micrograms of a preparation of naturally occurring bovine osteogenic protein mixed with the collagen carrier. Limbs that served as controls received either the collagen carrier alone or no implant at all. The treated and the untreated defects were examined radiographically and histologically at eight or twelve weeks after implantation. Mechanical testing was performed on six animals. All implants of recombinant human osteogenic protein-1, except for those containing 3.13 micrograms of the substance, induced complete radiographic osseous union within eight weeks. The defects that were treated with an implant of bovine osteogenic protein also healed within this time-period. The bone induced by both types of implants had new cortices with advanced remodeling and marrow elements. Histological evaluation of this new bone at eight weeks postoperatively revealed primarily lamellar bone, with the formation of new cortices and normal-appearing marrow elements. The average torsional strength and energy-absorption capacity of the union induced by recombinant human osteogenic protein-1 was comparable with that of intact bone. The control defects that had been implanted with collagen carrier alone and those with no implant showed no bridging of the defect. PMID- 8200891 TI - The usefulness of C-reactive protein levels in the identification of concurrent septic arthritis in children who have acute hematogenous osteomyelitis. A comparison with the usefulness of the erythrocyte sedimentation rate and the white blood-cell count. AB - Thirty-six children who had bacteriologically confirmed acute hematogenous osteomyelitis but did not have concurrent septic arthritis, and ten children who had confirmed acute hematogenous osteomyelitis and concurrent septic arthritis, were followed for one year to compare the changes in the C-reactive protein level in the blood, the erythrocyte sedimentation rate, and the white blood-cell count. In both groups, the mean C-reactive-protein values were high (eighty-four milligrams per liter in the children who had septic arthritis and osteomyelitis and sixty-five milligrams per liter in those who had osteomyelitis only) at the time of admission to the hospital. However, in the group that had septic arthritis, the increase was significantly higher (p < 0.01) as early as the second day and a normal level (less than twenty milligrams per liter) was reached significantly later (p < 0.001) than in the group that had osteomyelitis only (11 +/- 7 days compared with 6 +/- 3 days [mean and standard deviation]). The erythrocyte sedimentation rate showed the same tendency, but the difference in the rates between the groups did not become evident until the fifth to fourteenth days after admission. A normal erythrocyte sedimentation rate (less than twenty millimeters per hour) was reached in 25 +/- 12 days in the children who had septic arthritis and in 17 +/- 10 days in those who did not (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200892 TI - Total hip arthroplasty without cement in obese patients. A minimum two-year clinical and radiographic follow-up study. AB - A retrospective study of patients who had had a primary total hip arthroplasty without cement between 1983 and 1990 was done to examine differences in clinical and radiographic results between obese and normal-weight individuals. Patients were considered to be of normal weight if the body-mass index (calculated as weight in kilograms divided by height in meters squared) was between twenty and less than thirty, and they were considered to be obese if the body-mass index was thirty or more. There were 127 normal-weight patients (142 hips) and fifty-five obese patients (sixty hips) in the analysis. Eight obese patients (eight hips) who had a body-mass index of forty or more were considered to be morbidly obese and were examined separately as a subset of the obese group. The duration of follow-up averaged forty-eight months (range, twenty-four to ninety-two months). There were no differences between the groups with regard to age, diagnosis, the type of stem or cup, the type of bone, the postoperative level of activity, or the duration of follow-up. The obese patients had a significantly greater loss of blood during the operation than the patients in the normal-weight group. There were no significant differences between groups with regard to the prevalence of perioperative complications, the number of units of blood transfused, the operative duration, or the duration of hospitalization. Of the 202 hips, 184 (91 percent) were pain-free or only mildly painful at the latest follow-up examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200893 TI - Total hip arthroplasty with cement in patients who are less than fifty years old. A sixteen to twenty-two-year follow-up study. AB - Eighty-nine Charnley total hip arthroplasties were performed with cement, by a single surgeon, in sixty-seven patients who were less than fifty years old at the time of the procedure. The follow-up period ranged from sixteen to twenty-two years (average, eighteen years). The most recent evaluation consisted of a clinical and a radiographic examination for forty-six patients (fifty-eight hips), a telephone interview and a review of the most recent radiographs for eleven patients (sixteen hips), and a telephone interview only for six patients (ten hips). Four patients (five hips) were lost to follow-up. Eleven (13 per cent) of the eighty-four hips that were followed were revised because of aseptic loosening of the acetabular implant, and two hips (2 per cent) were revised because of aseptic failure (loosening or fracture) of the femoral component. When the number of hips that were revised was combined with the number of hips in which there was radiographic evidence of failure, the rate of loosening of the acetabular component was 50 per cent (forty-two hips) and the rate of failure of the femoral component was 8 per cent (seven hips). Three hips had recurrent dislocations after the operation; none of the three was revised. One patient (two hips) had Grade-III heterotopic ossification according to the system of Brooker et al.; no other patient had more than Grade-II heterotopic ossification. Nine hips had a trochanteric non-union without migration of the trochanter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200894 TI - Intramedullary arthrodesis of the knee after failed total knee arthroplasty. AB - Eighteen patients (eighteen knees) were managed with an intramedullary arthrodesis after a failed total knee arthroplasty. Twelve knees had had a revision total knee arthroplasty and six, a primary total knee arthroplasty. Three knees had had failure of a hinged prosthesis. In eleven knees, the arthroplasty had failed because of infection. Nine patients had had previous attempts at arthrodesis with external fixation. The average duration of the operation was six hours, and the average blood replacement was 2975 milliliters. A vascularized fibular pedicle graft was used in four patients. At a mean of thirty-seven months after the arthrodesis, sixteen of the eighteen patients had a complete radiographic union. The mean time to union was 5.5 months. Although a high rate of union was achieved in these patients, complications occurred in ten of the eighteen knees and this must be considered. Intramedullary arthrodesis is a successful method of salvage for a failed total knee arthroplasty or one complicated by infection that is not amenable to revision, but it is technically demanding and has frequent complications. PMID- 8200895 TI - Skeletal-extraskeletal angiomatosis. A clinicopathological study of fourteen patients and nosologic considerations. AB - We reviewed the consultation files of the ARmed Forces Institute of Pathology for 1951 through 1989 and identified fourteen patients who had had skeletal extraskeletal angiomatosis. Skeletal-extraskeletal angiomatosis was defined as a benign vascular proliferation involving the medullary cavity of bone and at least one other type of tissue. The age of the patients at the time of initial biopsy ranged from nine months to sixty-nine years (average, twenty-two years; median, ten years). Ten of the patients were male and four were female. The presenting signs and symptoms were highly variable; they included pain (four patients), a mass noted at birth (three patients), a painless mass that developed after birth (two patients), both pain and a mass (one patient), a localized deformity of the thoracic spine (one patient), and anemia associated with chronic bleeding of the gastrointestinal tract (one patient); in this last patient, skeletal lesions subsequently were found and biopsied. Skeletal-extraskeletal angiomatosis was an incidental finding in the remaining two patients. Multiple bones were involved in thirteen of the fourteen patients. Histologically, three patterns of lesion could be identified: cavernous lymphangioma (six patients), cavernous hemangioma (six patients), and arteriovenous hemangioma (two patients). Five of the patients died (three of sepsis associated with persistent lesions of angiomatosis and two of unrelated causes); eight of the patients survived but had residual disease, and one survived and had no evidence of residual disease. PMID- 8200896 TI - Melanoma of the foot. AB - We performed a prospective study of the results of treatment of primary cutaneous melanoma of the foot in 282 patients to determine if there were any factors that could predict survival. These patients were part of a group of 1018 patients who had primary cutaneous melanoma affecting the lower extremity. We found that 184 (65 per cent) of the 282 patients had a tumor that extended into the reticular dermis or subcutaneous tissue (a Level-IV or V lesion according to the system of Clark et al.). Sixty-three patients (22 per cent) had evidence of local, regional, or distant metastatic disease at the time of presentation. Location of the melanoma on the plantar aspect of the foot was found to be an independent variable that was associated with a poorer rate of survival (56 per cent at five years and 46 per cent at ten years) compared with a dorsally located melanoma (80 per cent at five years and 67 per cent at ten years). Subungual lesions were associated with an extremely low rate of survival (17 per cent at ten years); however, because of the small number of subungual lesions that were followed, the difference in survival between the patients who had a plantar lesion and those who had a subungual lesion was not significant (p = 0.52). Variables, in order of decreasing importance, that had independent prognostic significance for survival of patients who had a melanoma of the foot were the clinical stage of the lesion at the time of presentation (p < 0.001) and the age of the patient (p < 0.03), as determined by multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200897 TI - Fat embolism precipitated by reaming of the femoral canal during revision of a total knee replacement. A case report. PMID- 8200898 TI - Leiomyosarcoma of the femur in a patient with a history of retinoblastoma. A case report. PMID- 8200899 TI - Hemimelic progressive osseous heteroplasia. A case report. PMID- 8200900 TI - Entrapment of the ureter following indirect reduction of an acetabular fracture. A case report. PMID- 8200901 TI - Persistent leakage of cerebrospinal fluid after intrathecal administration of morphine in an operation on the lumbar spine. A report of two cases. PMID- 8200902 TI - The Food and Drug Administration's regulation of orthopaedic devices. PMID- 8200903 TI - Lateral extensor release for tennis elbow. PMID- 8200905 TI - Exposure of the orthopaedic surgeon to radiation. PMID- 8200904 TI - Antibiotic-leaching from polymethylmethacrylate beads. PMID- 8200906 TI - Cell cycle arrest by prostaglandin A1 at the G1/S phase interface with up regulation of oncogenes in S-49 cyc- cells. AB - Our previous studies have implied that prostaglandins inhibit cell growth independent of cAMP. Recent reports, however, have suggested that prostaglandin arrest of the cell cycle may be mediated through protein kinase A. In this report, in order to eliminate the role of c-AMP in prostaglandin mediated cell cycle arrest, we use the -49 lymphoma variant (cyc-) cells that lack adenylate cyclase activity. We demonstrate that dimethyl prostaglandin A1 (dmPGA1) inhibits DNA synthesis and cell growth in cyc- cells. DNA synthesis is inhibited 42% by dmPGA1 (50 microM) despite the fact that this cell line lacks cellular components needed for cAMP generation. The ability to decrease DNA synthesis depends upon the specific prostaglandin structure with the most effective form possessing the alpha, beta unsaturated ketone ring. Dimethyl PGA1 is most effective in inhibiting DNA synthesis in cyc- cells, with prostaglandins PGE1 and PGB1 being less potent inhibitors of DNA synthesis. DmPGE2 caused a significant stimulation of DNA synthesis. S-49 cyc- variant cells exposed to (30-50 microns) dmPGA1, arrested in the G1 phase of the cell cycle within 24 h. This growth arrest was reversed when the prostaglandin was removed from the cultured cells; growth resumed within hours showing that this treatment is not toxic. The S-49 cyc- cells were chosen not only for their lack of adenylate cyclase activity, but also because their cell cycle has been extensively studied and time requirements for G1, S, G2, and M phases are known. Within hours after prostaglandin removal the cells resume active DNA synthesis, and cell number doubles within 15 h suggesting rapid entry into S-phase DNA synthesis from the G1 cell cycle block.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8200907 TI - Isolation of cDNA clones from an osteosarcoma-ROS17/2.8 library by differential hybridization. AB - We have used differential hybridization to isolate and characterize two novel cDNAs expressed in chondrocytes and some osteoblastic cells. A rat osteosarcoma ROS17/2.8 cDNA library was screened and cDNA clones hybridizing strongly to radiolabeled porcine calvaria cDNA but weakly to a control radiolabeled cDNA were isolated. Two clones were obtained--p.6.1 and p.10.15. A radiolabeled probe of p10.15 was shown to hybridize specifically to a 2.3 Kb message RNA from a chondrogenic clonal cell population from rat calvaria-RCJ 3.1C5.18, and the mRNA was downregulated by 1,25 (OH)2D3, which inhibits chondrogenesis in these cells. The other clone, p6.1, was found to hybridize to a 0.95 Kb message that is expressed in rat liver, kidney, lung, muscle, and brain, but not expressed in spleen and expressed only in low levels in thymus. PMID- 8200908 TI - Specific region of the c-myc promoter is responsive to electric and magnetic fields. AB - The level of c-myc transcripts is increased in cells exposed to extremely low frequency (elf) electromagnetic (EM) fields at 60 Hz. The aim of the present experiments was to determine if regulatory regions upstream of the c-myc gene modulate the response to EM fields. DNA upstream of P1 of both mouse and human c myc genes was transfected into cells as CAT constructs. The presence of DNA 5' to the human or mouse myc genes results in increased expression of CAT following 20 min exposures of cells to 60 Hz elf EM fields. Specific portions of the human upstream DNA were deleted and introduced into cells. The region responsive to EM fields is located between -353 and -1,257 relative to the P1 promoter. PMID- 8200909 TI - Expression of estrogen receptors in estrogen receptor-negative human breast carcinoma cells: modulation of epidermal growth factor-receptor (EGF-R) and transforming growth factor alpha (TGF alpha) gene expression. AB - A number of studies suggest that an inverse correlation exists between the epidermal growth factor-receptor and the estrogen receptor expression in primary human breast carcinoma as well as in established human breast carcinoma cell lines. Recent studies suggest that the epidermal growth factor-receptor does not regulate the estrogen receptor gene expression. Whether the estrogen receptor regulates the epidermal growth factor-receptor gene expression is not known. We addressed this question by stably transfecting the estrogen receptor cDNA into the estrogen receptor-negative human breast carcinoma cell line MDA-MB-231. Constitutive expression of functional estrogen receptors in the transfectants resulted in increased mRNA levels of both epidermal growth factor-receptor and transforming growth factor alpha. Estradiol treatment of transfected cells, although enhancing transforming growth factor alpha mRNA levels, did not modulate epidermal growth factor-receptor mRNA levels. The estrogen receptor-transfected cells grown in estrogenic regular medium, however, exhibited lower constitutive levels of epidermal growth factor-receptor mRNA than in steroid-stripped medium, suggesting that estrogens coupled with some factors normally present in the regular medium may indeed downmodulate epidermal growth factor-receptor mRNA. Sodium butyrate treatment enhanced epidermal growth factor-receptor mRNA levels in nontransfected cells grown in regular estrogenic as well as in steroid stripped medium. Sodium butyrate enhancement of epidermal growth factor-receptor mRNA levels was completely abolished in estrogen receptor-transfected cells grown in regular estrogenic medium and blunted in steroid stripped medium. Using various epidermal growth factor-receptor gene promoter-CAT constructs in transient transfection assays, we further demonstrate that sodium butyrate enhanced transcription of the epidermal growth factor-receptor gene. The putative sodium butyrate responsive element(s) appears to localize within the proximal 384 bp of the epidermal growth factor-receptor gene promoter region. Although the interactions between estrogen receptor and epidermal growth factor-receptor are rather complex, taken together, our data suggest that estrogen receptor can indeed modulate the epidermal growth factor-receptor mRNA expression. PMID- 8200911 TI - Guanine nucleotide binding regulatory proteins in liver from obese humans with and without type II diabetes: evidence for altered "cross-talk" between the insulin receptor and Gi-proteins. AB - A novel pathway for physiological "cross-talk" between the insulin receptor and the regulatory Gi-protein has been demonstrated. We tested the hypothesis that a coupling defect between Gi and the insulin receptor is present in the liver of obese patients with and without type II diabetes. Insulin 1 x 10(-9) M (approximately ED50) and 1 x 10(-7) M (Max) inhibited pertussis toxin-catalyzed ADP ribosylation of Gi in human liver plasma membranes from lean and obese nondiabetic patients. However, 1 x 10(-7) M insulin was without effect in membranes from patients with type II diabetes. This coupling defect was not intrinsic to Gi, since Mg2+ and GTP gamma S inhibited pertussis toxin-catalyzed ADP ribosylation in both diabetic and nondiabetic patients. Binding of insulin of the alpha-subunit and activation of the tyrosine kinase intrinsic to the beta subunit of the insulin receptor are not responsible for the coupling defect. 125I insulin binding is the same in obese patients with or without diabetes. Tyrosine kinase of the insulin receptor is decreased in diabetes. However, a monoclonal antibody to the insulin receptor (MA-20) at equimolar concentrations with insulin equally inhibits pertussis toxin-catalyzed ADP ribosylation of Gi without activating tyrosine kinase or insulin receptor autophosphorylation. Immunodetection of G-proteins suggested that Gi3 alpha was normal in diabetes and Gi1-2 alpha was decreased by 40% in the diabetic group as compared to the obese nondiabetic group but was normal when compared to the lean non diabetic group. We conclude that the novel pathway of insulin signaling involving the regulatory Gi proteins via biochemical mechanisms not directly involving the tyrosine kinase of the insulin receptor is altered in obese type II diabetes and offers a new target for the search of the mechanism(s) of insulin resistance. PMID- 8200910 TI - Apolipoprotein E: a potent inhibitor of endothelial and tumor cell proliferation. AB - Recombinant human apolipoprotein E3 (apoE), purified from E. coli, inhibited the proliferation of several cell types, including endothelial cells and tumor cells in a dose- and time-dependent manner. ApoE inhibited both de novo DNA synthesis and proliferation as assessed by an increase in cell number. Maximal inhibition of cell growth by apoE was achieved under conditions where proliferation was dependent on heparin-binding growth factors. Thus, at low serum concentrations (0 2.5%) basic fibroblast growth factor (bFGF) stimulated the proliferation of bovine aortic endothelial (BAE) cells severalfold. The bFGF-dependent proliferation was dramatically inhibited by apoE with an IC50 approximately 50 nM. Under conditions where cell proliferation was mainly serum-dependent, apoE also suppressed growth but required higher concentrations to be effective (IC50 approximately 500 nM). ApoE also inhibited growth of bovine corneal endothelial cells, human melanoma cells, and human breast carcinoma cells. The IC50 values obtained with these cells were generally 3-5 times higher than with BAE cells. Inhibition of cell proliferation by apoE was reversible and dependent on the time of apoE addition to the culture. In addition, apoE inhibited the chemotactic response of endothelial cells that were induced to migrate by a gradient of soluble bFGF. Inhibition of cell proliferation by apoE may be mediated both by competition for growth factor binding to proteoglycans and by an antiadhesive activity of apoE. The present results demonstrate that apoE is a potent inhibitor of proliferation of several cell types and suggest that apoE may be effective in modulating angiogenesis, tumor cell growth, and metastasis. PMID- 8200912 TI - Induction of cell surface peptidase activity: a global response to cell stress correlated with apoptosis. AB - We have previously characterized the stimulation of HeLa cell surface peptidase activity directed toward a nonapeptide substrate in response to low fluences of ultraviolet irradiation [Brown et al. (1993): J Cell Biochem 51:102-115]. To explore the hypothesis that this comprised a global response to cell stress featuring the interruption of DNA synthesis, a variety of agents affecting macromolecular synthesis were applied to HeLa cell cultures. Actinomycin D, 5,6 dichloro-1 beta-ribofuranosyl benzimadazole, mitomycin C, ultraviolet light, and cycloheximide at doses which inhibited cell growth, but fell short of increasing the proportion of cells which had lost cell membrane impermeability to trypan blue, resulted in the concentration dependent increase in both amino- and endo peptidase activities of intact HeLa cell cultures. gamma-Irradiation, despite inhibiting an increase in cell number over a 20-h observation period, had no effect on the expressed level of cell surface peptidase activity nor did the accumulation of cells in S or G2 phase by thymidine parasynchronization. Some of these agents were found to increase the proportion of cells in the culture undergoing apoptosis (programmed cell death), and a strong correlation was found between the extent of apoptosis and the degree of elevation in cell surface peptidase activity. Higher concentrations of perturbants in some instances increased the percentage of cells that were nonviable and an associated release of intracellular proteases overwhelmed the linear correlation with apoptotic cells. The present data do not distinguish between a homogeneous elevation of surface peptidase activity in all cells of treated cultures or the heterogeneous increase in only preapoptotic or apoptotic cells. Since sunburn of the skin increases both the occurrence of apoptotic keratinocytes (sunburn cells) in the affected epidermis and the release of membrane bound cell activators such as transforming growth factor alpha, it is suggested by way of extrapolation of these in vitro results, that the increase in cell surface proteolytic activity plays an integral part in the reparative responses of the epidermal cells in vivo. PMID- 8200913 TI - Absence of transforming growth factor-beta responsiveness in the tamoxifen growth inhibited human breast cancer cell line CAMA-1. AB - Tamoxifen has been an effective antiestrogen in suppressing breast cancer growth which is estrogen-responsive or dependent. Early studies have provided circumstantial evidence that transforming growth factor-beta (TGF-beta) may be an autocrine mediator of tamoxifen action. Therefore, it is both fundamentally important and clinically relevant to investigate the relationship between tamoxifen and TGF-beta. In this study, we demonstrated that CAMA-1 cells, which are sensitive to tamoxifen inhibition, did not respond to TGF-beta growth inhibition. The type I and II TGF-beta receptors were undetectable by the radio ligand affinity labeling technique. Despite the presence of a normal TGF-beta type II receptor gene, the mRNA transcript of the gene was undetectable by the extremely sensitive Intron-differential RNA/PCR method. The possibility that the lack of TGF-beta receptors might be intimately linked to the absence of normal retinoblastoma (Rb) gene products, as suggested by previous studies of retinoblastoma cells, was further investigated. The lack of TGF-beta receptor expression was found due to reasons other than the absence, deletion or abnormality of the Rb gene because a normal Rb gene and its hyper- and hypo phosphorylated protein products were detected in CAMA-1 cells. In conclusion, our results suggest that the TGF-beta system is not obligatory for antiestrogen growth inhibition of CAMA-1 cells. PMID- 8200914 TI - Cell attachment peptide of C-reactive protein: critical amino acids and minimum length. AB - Human C-reactive protein (CRP) is an acute phase blood component that accumulates at sites of tissue damage and necrosis and is degraded by neutrophils to biologically active peptides. A dodecapeptide composed of amino acids 27-38 of CRP mediates cell attachment in vitro. This peptide was designated the cell binding peptide (CB-Pep) of CRP. Characterization of the interaction between fibroblasts and modified synthetic peptides with sequential deletions from either the N-terminus or C-terminus revealed that the minimal sequence for cell attachment or inhibition of cell attachment to the CB-Pep was Phe-Thr-Val-Cys Leu, which corresponds to residues 33-37 within each of the five 206 amino acid subunits of CRP. The pentapeptide by itself mediated cell attachment. Substitutions for each residue within the CB-Pep indicated that the critical residues for activity were Phe-33 and Thr-34. This cell-binding pentapeptide represents a recognition motif for cell adhesion not found in other proteins. PMID- 8200915 TI - Marrow stromal cell commitment to mineralization under the effect of a prolyl hydroxylase inhibitor. AB - Mitochondrial response to the effect of a hydroxylase (PH) inhibitor was tested in marrow stromal cells during stimulation of osteoprogenitor cell (OPC) differentiation. The rationale for this was to explore pathways of regulatory interactions between procollagen synthesis and mitochondrial respiration that could be linked to the commitment of OPCs to mineralization. Stimulated OPCs exposed to the PH inhibitor cis-hydroxyproline (cis-HP), compared to the noninhibiting isomer trans-HP, for 11 days showed a dose-dependent decrease in cell proliferation, the surviving cells showed increased alkaline phosphatase activity. Trans-HP did not influence the cis-HP effect on ALP and on proliferation arrest. Short time exposures, 2-3 days, to cis-HP at different periods suggested that Days 0-3 and 3-5 were critical for the commitment to Day 21 mineralization of OPCs. On Days 0-3 cells were most sensitive to cis-HP, since on Day 11, 8 days after removal of cis-HP, they were too scarce to be counted by the staining method. However, the presence of 5.0 mM cis-HP in the cultures during Days 3-5 has induced on Day 21 close to 24-fold more mineralization/cell than controls, compared to the trans-HP effect, which was only close to 3-fold. The presence of cis-HP in the cultures on Days 0-3 has augmented the mitochondrial Day 3 retention of rhodamine 123 (Rho) in the stromal cells, relative to controls, compared to the presence of trans-HP. However, the presence of cis-HP during Days 3-5 or 3-6 resulted in lower Day 5 Rho retention, relative to controls, which was not significantly different from the retention that resulted from trans-HP. Since Rho retention is related to the final result of aerobic respiration level, these results are interpreted as a cis-HP inhibitory effect on procollagen peptidyl-proline hydroxylation, which may in turn release oxygen surpluses, to be available for mitochondrial consumption. The fall in Rho retention responses to cis-HP between Days 0-3 and 3-5 is suggesting either abrupt decrease in proline hydroxylation or poor mitochondrial sensitivity to oxygen in Day 3-5 cultures. PMID- 8200916 TI - Interleukin 4 increases type 5 acid phosphatase mRNA expression in murine bone marrow macrophages. AB - Type 5 acid phosphatase is a lysosomal enzyme expressed in cells of monocyte/macrophage lineage frequently used as a marker of osteoclastic differentiation. Oligonucleotide primers for DNA amplification were designed following sequence alignment of rat bone and human macrophage type 5 acid phosphatases. DNA (330 bp in length) obtained using these primers and reverse transcribed total cell RNA from in vitro generated murine osteoclastic cells was cloned and sequenced. DNA sequence analysis of two clones demonstrates that the amplified material was 91% and 96% identical to rat bone type 5 acid phosphatase at the nucleotide and amino acid level, respectively. Northern blots of murine tissue RNA show the presence of 1.5-kb transcripts that are most highly expressed in the long bones. Total cell RNA from the osteoclastic cells contain a marked level of type 5 acid phosphatase mRNA when compared to the levels seen in the tissue samples. Additionally, osteoclastic cell RNA contains two additional transcripts of 2.5 and 5 kb. Bone marrow macrophages grown in the presence of M CSF express low levels of the 1.5-kb transcript with no signal observed for either of the two larger transcripts that were seen in the osteoclastic RNA samples. Importantly, bone marrow macrophage 1.5-kb type 5 acid phosphatase transcript levels are increased by interleukin 4 treatment in both a time and concentration-dependent manner. These findings indicate that type 5 acid phosphatase, while a cytochemical marker for osteoclasts, can be induced in macrophages by agents that block in vitro osteoclastic differentiation. Increased type 5 acid phosphatase may play a role in interleukin 4-stimulated monocyte activities. PMID- 8200917 TI - Retention behavior of conjugated metabolites of vitamin D and related compounds in high-performance liquid chromatography. AB - The retention behavior of sulfates or glucuronides of provitamin D, vitamin D, and 25-hydroxyvitamin D3, together with its fluorescent derivatives, are examined with reversed-phase high-performance liquid chromatography. Inclusion chromatography using cyclodextrin as a mobile-phase additive is also used for this purpose. Conventional reversed-phase high-performance liquid chromatography clearly separates the positionally isomeric conjugates of 25-hydroxyvitamin D3. The addition of the host compound to the mobile phase is effective in separating the pairs of fluorescent derivatives of vitamin-D3 and -D2 conjugates or provitamin-D3 and -D2 conjugates. PMID- 8200918 TI - Quantitation of formaldehyde, acetaldehyde, and acetone in sidestream cigarette smoke by high-performance liquid chromatography. AB - A method is described for the collection and quantitation of formaldehyde, acetaldehyde, and acetone in sidestream cigarette smoke. Using the "fishtail" chimney procedure (1), sidestream smoke is drawn by vacuum through the chimney, a Cambridge filter pad (Performance Systematics Inc.; Caledonia, MI), and into an impinger containing a solution of 2,4-dinitrophenylhydrazine (DNPH), whose solubility in acetonitrile was increased by using diglyme as a constituent of the collection derivatization solution. The chimney is rinsed with DNPH solution to remove "formaldehyde", and the rinse is added to the impinger solution. This combined wash and impinger solution is used to extract the Cambridge pad. An aliquot of the extract is analyzed by high-performance liquid chromatography using a reversed-phase column, ultraviolet detection, and a mobile phase gradient with tetrahydrofuran as a modifier. Acrolein is detected but gives poor precision and recovery because of dimer formation. For formaldehyde, acetaldehyde, and acetone, both the precision (7.30, 2.49, 2.88% relative standard deviation, respectively) and recovery (90.0, 95.2, 102.8%, respectively) are acceptable. The response for formaldehyde, acetaldehyde, and acetone is linear and a function of the number of cigarettes smoked. The minimum detectable quantity for the analytes ranges from 5 to 16 micrograms per cigarette. PMID- 8200919 TI - Supercritical fluid chromatography of garlic (Allium sativum) extracts with mass spectrometric identification of allicin. AB - Supercritical fluid chromatography-mass spectrometry has been used successfully to identify allicin (2-propene-1-sulfinothioic acid S-2-propenyl ester), the predominant thiosulfinate in freshly cut garlic (Allium sativum). A low oven temperature (50 degrees C) and low restrictor tip temperature (115 degrees C) were needed in order to obtain a chemical ionization (CI) mass spectrum of allicin with the protonated molecular ion, m/z 163, as the major ion. The effects of tip temperature on the CI mass spectrum of allicin are presented. PMID- 8200920 TI - The reliability of a solid-phase extraction system for the analysis of benzoylecgonine in urine. AB - Gas chromatographic-mass spectrometric (GC-MS) analysis for benzoylecgonine (BE), a metabolite of cocaine, requires an initial extraction from urine. Although liquid-liquid extraction methods are frequently used, solid-phase extraction (SPE) may be preferable for obtaining reliable results and clean chromatograms. We describe a 12-month study that evaluates the accuracy, precision, variability between analysts, variability between column lots, and cleanliness of BE extracts using SPE columns followed by GC-MS analysis. The overall mean for a control urine sample prepared at 150 ng/mL is 151 ng/mL (N = 293) with a standard deviation of 8.59 and a coefficient of variation (CV) of 5.7%. Within-run precision (measured as CV) at 75, 150, and 2000 ng/mL is 4.0, 1.8, and 0.8%, respectively. Mean results from 10 different analysts vary a maximum of 4.6% from the overall mean of 151 ng/mL, and the CV for 9 out of 10 analysts is 7.0% or less. The CV for the remaining analyst is 10.4%. Quantitative results from nine different lots of SPE columns fluctuate 3.3% from the overall mean of 151 ng/mL, and the CV varies from 3.5 to 6.2%. GC-MS chromatograms following SPE are significantly cleaner (i.e., reduced baseline signal and no interfering peaks) than those from two types of liquid-liquid extractions. PMID- 8200921 TI - Conformer interconversion in the LC analysis of triostin A and its under-N methylated synthetic analogue. AB - Multiple peak formation and interconversion in the liquid chromatographic (LC) analysis of triostin A and its under-N-methylated synthetic analogue, [N-MeCys3,N MeCys7]-TANDEM (MCTANDEM), are investigated as a function of column temperature. Slow interconversion between chromatographic peaks, ascribed to the presence of the n- and p-solution conformers of the peptides, is exhibited in the normal phase elution profiles of triostin A and in the reversed-phase elution profiles of MCTANDEM. A chromatographic model is developed to estimate the kinetics of conformer interconversion. Reversed-phase LC analysis of the n- and p-conformers of MCTANDEM yields a value of 0.01/s for the apparent interconversion rate constant (kn-p) at 25 degrees C, with a corresponding activation energy of 16 kcal/mol. Normal-phase LC analysis of the n- and p-conformer interconversion of triostin A dissolved in chloroform results in a value of 0.04/s for kn-p at 25 degrees C, with a corresponding activation energy of 18 kcal/mol. For triostin A, normal-phase LC findings as a function of column temperature are compared with 1H nuclear magnetic resonance (NMR) line-width measurements between 80 degrees C and 140 degrees C for the n- and p-conformers, which yield an activation energy of 19 kcal/mol and an extrapolated value of 0.02/s at 25 degrees C for kn-p in deuteriochloroform. PMID- 8200922 TI - Simultaneous determination of verapamil and celiprolol in human plasma. AB - A simple and reproducible method for the simultaneous determination of the beta 1 selective adrenergic blocker, celiprolol, and the calcium antagonist, verapamil, in human plasma is described. It involves a two-step liquid-liquid extraction and separation using a C18 column with ultraviolet detection at 237 nm. Deacetyldiltiazem is used as the internal standard. Within-day and between-day coefficients of variation are less than 10%. The lower limits of detection are 4, 2, and 4 ng/mL for celiprolol, deacetyldiltiazem, and verapamil, respectively. The assay has clinical applicability. PMID- 8200923 TI - A selective separation of alcoholic beverages and distilled wines by gas chromatography. AB - The MFE-Vinicol column (Analisis Vinicos; Spain) was developed for the analysis of alcoholic beverages. Fusel alcohols at low concentrations, including 2 propanol, methanol, ethyl acetate, and ethyl butyrate, are determined by a single temperature-programmed analysis using this column. This column has important advantages over the official columns recommended by the Association of Official Analytical Chemists and other official methods for this kind of analysis. PMID- 8200924 TI - Clinical review 58: Creutzfeldt-Jakob disease in recipients of pituitary hormones. PMID- 8200925 TI - Growth disorders after cranial radiation in childhood. PMID- 8200926 TI - Cranial irradiation and early puberty. AB - Low doses of cranial irradiation (18-24 gray) employed in the management of acute lymphoblastic leukemia may cause early or precocious puberty, predominantly in girls. To determine whether this sexual dichotomy exists at higher irradiation doses (25-47 gray), the onset of puberty was identified in 46 GH-deficient children (30 males) previously irradiated for a brain tumor not involving the hypothalamic-pituitary axis and compared with the normal pubertal standards of Marshall and Tanner. Age at irradiation was at least 2 SD below the mean age of pubertal onset in normal children. There was a significant linear association between age at irradiation and age at onset of puberty. The onset of puberty occurred at an early age in both sexes (mean, 8.51 yr in girls and 9.21 yr in boys plus 0.29 yr for every year of age at irradiation). For example, the estimated age at onset of puberty in a boy irradiated at 2 yr of age would be 9.79 yr, and that for a boy irradiated at 9 yr of age would be 11.82 yr. In the context of GH deficiency, which is usually associated with a delay in the onset of puberty, this is abnormal. At each age of irradiation, the estimated age at the onset of puberty was approximately 0.7 yr earlier in girls than boys. A similar trend was seen for bone age, which was abnormally early at the time of pubertal onset (mean, 7.39 yr in girls and 8.66 yr in boys plus 0.25 yr for every year of age at the time of irradiation). At the doses of irradiation employed in the treatment of brain tumors, radiation-induced early puberty is not restricted to girls. The clinical consequence of early puberty in the management of poor growth associated with radiation-induced GH deficiency is to foreshorten the time available for treatment with GH. PMID- 8200927 TI - A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom). AB - We report the features of a new syndrome of aromatase deficiency due to molecular defects in the CYP19 (P450arom) gene in a 46,XX female. At birth, the patient presented with a nonadrenal form of female pseudohermaphrodism. At 17 months of age, laparotomy revealed normal female internal genital structures; the histological appearance of the ovaries was normal. FSH concentrations were markedly elevated at 9.4 ng/mL LER 869, and estrone and estradiol levels were undetectable (< 37 pmol/L). By 14 yr of age, she had failed to exhibit breast development. The clitoris had enlarged to 4 x 2 cm, and pubic hair was Tanner stage IV. The plasma concentration of testosterone was elevated at 3294 pmol/L, as was androstenedione at 9951 pmol/L. Plasma estradiol levels were below 37 pmol/L. ACTH and dexamethasone tests indicated a nonadrenal source of testosterone and androstenedione. Plasma gonadotropin levels were in the castrate range. Pelvic sonography and magnetic resonance imaging showed multiple 4- to 6 cm ovarian cysts bilaterally. Despite increased circulating androgens and clitoral growth, the bone age was 10 yr at chronologic age 14 2/12 yr. Estrogen replacement therapy resulted in a growth spurt, breast development, menarche, suppression of gonadotropin levels, and resolution of the cysts. The clinical findings suggested the diagnosis of P450arom deficiency. Analyses of genomic DNA from ovarian fibroblasts demonstrated two single base changes in the coding region of the P450arom gene, one at 1303 basepairs (C-T), R435C, and the other at 1310 basepairs (G-A), C437Y, in exon 10. The molecular genetic studies indicate that the patient is a compound heterozygote for these mutations. Expression of these mutations showed that the R435C mutation had 1.1% the activity of the wild type P450arom enzyme, whereas the C437Y mutation demonstrated no activity. The cardinal features of this syndrome are a consequence of P450arom deficiency: 1) the fetal masculinization in this syndrome can be ascribed to defective placental conversion of C19 steroids to estrogens, leading to exposure of the female fetus to excessive amounts of testosterone; 2) the pubertal failure, mild virilization, multicystic ovaries, and hyperstimulation of the ovaries by FSH and LH are the result of the inability of the ovary to aromatize testosterone and androstenedione to estrogens; and 3) the striking delay in bone age at 14 2/12 yr supports the notion that estrogens, in contrast to androgens, are the major sex steroid driving skeletal maturation during puberty. Familial P450arom deficiency, although rare, may be more common than previously suspected.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8200928 TI - Gonadotropin-releasing hormone-dependent chorionic gonadotropin secretion in a menopausal woman. AB - We report the evaluation of a 46-yr-old asymptomatic menopausal woman whose serum hCG concentrations remained persistently supra-normal for 3 yr (mean +/- SD, 20 +/- 10 IU/L; n = 19). Holo-hCG and beta-core fragments were detected in the patient's urine by Ultragel chromatography, followed by specific RIAs. Trophoblastic, germ cell, and other malignancies appeared to be excluded by the absence of serum tumor markers and imaging procedures of the pelvis, abdomen, breast, and chest. Administration of a single bolus dose of synthetic GnRH (100 micrograms) increased the serum hCG concentration by 50% (from 26 to 40 IU/L). Administration of the Nal-Glu GnRH antagonist (5 mg, sc, every 12 h for 1 week) decreased the serum hCG concentration from 27 to 4.6 IU/L. The pronounced decrease in the serum hCG concentration during antagonism of the action of endogenous GnRH by administration of Nal-Glu GnRH suggests that the pituitary is the source of the supra-normal serum hCG concentrations, because the pituitary is exposed to the highest concentration of endogenous GnRH. PMID- 8200929 TI - Alterations in growth hormone secretion and clearance in peripubertal boys with chronic renal failure and after renal transplantation. Cooperative Study Group of Pubertal development in Chronic Renal Failure. AB - To elucidate the endocrine mechanisms underlying the pubertal growth failure observed in patients with chronic renal failure (CRF), we used deconvolution analysis to estimate the rates of GH secretion and elimination in nighttime plasma GH profiles of peripubertal boys with CRF and after renal transplantation (Tx). Forty-three boys with advanced CRF (conservative treatment with glomerular filtration rate < 25 mL/min.1.73 m2 or dialysis; CT/D group), 38 boys after Tx, and 40 healthy control boys were studied. The estimated plasma GH half-life (mean +/- SEM) was significantly higher (P < 0.05) in CRF (25 +/- 1.8 min) than in Tx patients (21 +/- 1.6 min) and controls (20 +/- 0.5 min). In the pre- and early pubertal CT/D boys, the calculated GH secretion rate was low normal or reduced when expressed in absolute numbers or normalized per unit distribution volume or body surface. In late puberty, whereas body surface-corrected GH secretion was double the prepubertal value in normal boys (389 +/- 56 vs. 868 +/- 113 micrograms/m2.11 h; P < 0.01), it did not differ significantly from the prepubertal rate in CT/D boys (281 +/- 59 vs. 389 +/- 56 micrograms/m2.11 h). GH hyposecretion resulted from a decrease in the mass of GH released within each burst, whereas burst frequency was unchanged. In the Tx group, GH secretion rates were significantly reduced in the prepubertal (221 +/- 39 micrograms/m2.11 h; P < 0.05) and late pubertal period (266 +/- 64 micrograms/m2.11 h; P < 0.01). The mass of hormone secreted per burst was significantly reduced at each pubertal stage, whereas GH secretory burst frequency tended to be increased (significant in prepubertal group, P < 0.05). The GH secretion rate was positively correlated with plasma testosterone levels (r = 0.58; P < 0.0001) in controls, but not in CT/D or Tx patients. GH secretion rates were lower than expected at each level of plasma testosterone in both patient groups except CT/D boys with plasma testosterone below 0.9 nmol/L. In the Tx group, GH secretion rate was positively correlated with relative height (r = 0.31; P < 0.05). The dosage of corticosteroids administered for immunosuppression was negatively correlated with GH burst mass (r = -0.42; P < 0.01) and GH secretion rate (r = -0.29; P = 0.08) and positively correlated with GH burst frequency (r = 0.49; P < 0.01). We conclude that in peripubertal boys with CRF, a state of GH hyposecretion is associated with an increase in the apparent plasma half-life of GH.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8200930 TI - Transcription of brain natriuretic peptide and atrial natriuretic peptide genes in human tissues. AB - We have compared the expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) genes in various human tissues using a quantitative polymerase chain reaction technique. Tissues of three human subjects, obtained at autopsy, were analyzed. BNP transcripts could be detected in the central nervous system, lung, thyroid, adrenal, kidney, spleen, small intestine, ovary, uterus, and striated muscle. ANP transcripts could also be demonstrated in various human extracardiac tissues including several endocrine organs. In all peripheral tissues, the level of both natriuretic peptide transcripts was approximately 1-2 orders of magnitude lower than in cardiac ventricular tissues. This distribution is in marked contrast to the much lower level of ANP and BNP transcripts present in extracardiac rat tissues (generally less than 1/1000 of ventricles). These data suggest differential expression of the two natriuretic peptide genes in cardiac and extracardiac tissues in man. Furthermore, the presence of local synthesis of ANP and BNP in various peripheral organs suggests paracrine and/or autocrine function of these natriuretic peptides. PMID- 8200931 TI - Enhanced sensitivity growth hormone (GH) chemiluminescence assay reveals lower postglucose nadir GH concentrations in men than women. AB - Modifications were made to a commercially available human (h) GH chemiluminescence assay (Nichols Luma Tag hGH assay), which improved its sensitivity to 0.002 micrograms/L. The results of this assay had a high correlation with those of the Nichols hGH immunoradiometric assay (IRMA; r = 0.91; P < 0.001). The addition of recombinant hGH-binding protein (0.1-10 nmol/L) to standards and serum samples caused a dose-responsive reduction in measured GH in both the chemiluminescence assay and the IRMA; at physiological concentrations of hGH-binding protein, a 10-20% reduction was observed. Fifteen normal young adults (nine men and six women) underwent a standard 100-g oral glucose tolerance test, and plasma GH was measured from 30 min before until 5 h after glucose ingestion. GH was measurable in all samples with the chemiluminescence assay, but fell below the sensitivity of the IRMA in 59% of the samples. There was no difference between baseline or peak glucose levels in male and female subjects, but serum GH concentrations (mean +/- SD) measured by the enhanced sensitivity chemiluminescence assay were lower in male than female subjects at both baseline (0.12 +/- 0.08 vs. 2.3 +/- 2.3 micrograms/L; P < 0.01) and the postglucose GH nadir (0.029 +/- 0.014 vs. 0.25 +/- 0.23 micrograms/L; P < 0.01). The high correlation between baseline and nadir GH (r = 0.82; P < 0.001) and the equivalent fractional decline in mean GH levels in men and women after glucose administration (67 +/- 17% vs. 84 +/- 8%; P = 0.06) suggest that the lower GH levels in men after glucose treatment are due to lower baseline values and not to a greater suppressive effect of glucose. PMID- 8200932 TI - p53 abnormalities in human parathyroid carcinoma. AB - Two cell cycle regulators have been implicated in the pathogenesis of parathyroid neoplasms: rearrangement/overexpression of the PRAD1/cyclin D1 gene in parathyroid adenomas and inactivation of the retinoblastoma tumor suppressor gene in parathyroid carcinomas. We examined parathyroid tumors for evidence of molecular genetic abnormalities in another cell cycle regulator, the p53 tumor suppressor gene. Allelic loss of the p53 gene was observed in parathyroid carcinomas from 2 of 6 genetically informative patients. Moreover, 2 of 9 patients' parathyroid carcinomas had nuclear p53 protein detectable by immunohistochemical analysis, a finding that often reflects mutational stabilization of the p53 protein. Of these two p53-immunopositive carcinomas, 1 had p53 allelic loss and 1 was genetically uninformative. In contrast, none of 20 informative parathyroid adenomas exhibited p53 allelic loss; 1 of 19 adenomas had a focal region of nuclear p53 protein staining. Single strand conformation polymorphism analysis of exons 5-9 of the p53 gene did not reveal mutations in any parathyroid neoplasm, suggesting that such mutations in parathyroid tumors may lie outside of these conserved regions. The finding of both p53 allelic loss and abnormal p53 protein expression in parathyroid carcinomas implicates p53 in the pathogenesis of a subset of these tumors. PMID- 8200933 TI - Reduced concentration of serum growth hormone-binding protein in children with idiopathic short stature. National Cooperative Growth Study. AB - One possible explanation for the growth failure in children with idiopathic short stature (ISS) is reduced peripheral responsiveness to GH. In Laron syndrome, growth retardation is caused by GH resistance due to GH receptor (GH-R) defects, which are associated in most cases with absent or low serum concentrations of the GH-R-related GH-binding protein (GHBP). We tested the hypothesis that some children with ISS have reduced serum concentrations of GHBP and that this may reflect decreased sensitivity to GH. A ligand-mediated immunofunctional assay was used to measure biochemically active GHBP in serum from 1549 children, including 773 controls, 573 with ISS, 107 with GH deficiency (GHD), and 96 with Turner syndrome (TS). Ages ranged from 1-17 yr. Serum GHBP concentrations in children with GHD, ISS, and TS were converted to SD scores and compared to controls by analysis of variance. In male and female ISS subjects, approximately 90% had GHBP concentrations below the age- and sex-adjusted mean for controls, and 20% had GHBP concentrations below the normal range. The mean serum GHBP SD score was lower in both males and females with GHD (-0.6) or ISS (-1.2) than in controls (both P < 0.005). The mean for ISS males was significantly lower than that for GHD males (P < 0.0001). The mean GHBP SD score for girls with TS (-0.3) did not differ significantly from that of the control females. The decreased levels of serum GHBP in some children with idiopathic short stature suggest that these children could have a defect at the level of the GH-R. PMID- 8200934 TI - Adrenal medulla secretion in Cushing's syndrome. AB - To investigate whether chronic endogenous hypercortisolism might alter adrenomedullary phenylethanolamine N-methyltransferase activity, we measured epinephrine/norepinephrine (E/NE) ratios in the adrenal venous blood of 8 patients undergoing surgery for Cushing's syndrome and in 12 control subjects undergoing surgery for left kidney diseases. To investigate the adrenomedullary secretory activity in Cushing's syndrome, we measured basal E plasma levels in 24 patients and 32 age- and sex-matched normal control subjects, and we evaluated the adrenomedullary response to glucagon in 9 patients and in 22 age- and sex matched normal subjects. Last, to clarify whether chronic endogenous hypercortisolism might modify E plasma levels through a modification of E metabolism, we measured the E MCR in four patients and four age-matched controls. Mean (+/- SEM) E/NE ratio in adrenal venous blood was similar in patients with Cushing's syndrome (4.61 +/- 0.78) and in the control group (4.71 +/- 0.74). Mean (+/- SEM) basal plasma E was significantly lower in patients with Cushing's syndrome (98.2 +/- 10.9 vs. 184 +/- 25.1 pmol/L, P < 0.01) than in the control group. Similarly, plasma NE also was reduced (0.75 +/- 0.09 vs. 1.10 +/- 0.07 nmol/L, P < 0.01). In patients with Cushing's syndrome the E response to glucagon was significantly reduced (P < 0.01). E MCR was almost identical in patients with Cushing's syndrome (1.48 +/- 0.10 L/min.m2) and in control subjects (1.51 +/- 0.10 L/min.m2). Our data demonstrate that: 1) chronic endogenous hypercortisolism is not able to change adrenomedullary phenylethanolamine N-methyltransferase activity and therefore the quality of adrenomedullary secretion; and 2) chronic endogenous hypercortisolism causes a decrease in basal and stimulated adrenomedullary activity without altering E MCR significantly. Therefore the adrenal medulla does not seem to play a pathogenetic role in the hypertension of Cushing's syndrome. PMID- 8200936 TI - Altered responses to hypoglycemia of healthy elderly people. AB - Many elderly people are treated with medications or are subjected to diseases which can cause hypoglycemia. We conducted the following studies to assess whether alterations in counterregulatory hormone release, decreased awareness of warning symptoms or alterations in psychomotor performance might increase the susceptibility of the elderly to hypoglycemia. Healthy, nonobese young (n = 10, age < 30) and old (n = 9, age > 65) subjects underwent paired hyperinsulinaemic clamp studies (insulin infusion rate 60 mU/m2.min). In the control study, glucose was kept at 5.0 mmol/L for 5 h. In the hypoglycemic study, glucose was kept at 5 mmol/L for 1 h and was lowered in stepwise fashion to 4.4, 3.8, 3.3, and 2.8 mmol/L in each subsequent hour. Subjects were blinded as to which study they were undergoing. Counterregulatory hormones were measured and a hypoglycemic symptom checklist was administered every 15 min in each study. Neuropsychological tests were performed at regular intervals. The glucose threshold for release of counterregulatory hormones was defined as the glucose level at which the values during the hypoglycemic study first exceeded values during the control study by 2 SD. The glucose threshold for glucagon and epinephrine release was higher in the young (approximately 3.3 mmol/L) than the old (approximately 2.8 mmol/L) and the epinephrine responses to hypoglycemia were also greater in the young. The threshold for release of GH (approximately 3.3 mmol/L) and norepinephrine and cortisol (approximately 2.8 mmol/L) was similar in each age group, as was the magnitude of release of these hormones. Although the variance in symptoms scores was large, the elderly appeared to have reduced awareness of the autonomic but not neuroglycopenic symptoms of hypoglycemia. There was no difference between young and old in the effect of hypoglycemia on neuropsychologic tests. We conclude that healthy elderly people may have impaired release of glucagon and epinephrine in response to hypoglycemia and reduced awareness of the autonomic symptoms of hypoglycemia. PMID- 8200935 TI - Maturation of the normal pituitary-testicular axis, as assessed by gonadotropin releasing hormone agonist challenge. AB - Pilot studies in boys with abnormalities of puberty have suggested that both gonadotropin and sex steroid responses to GnRH agonist undergo characteristic maturational changes. However, it is not known how the pattern of hormonal secretory responses to GnRH agonist changes during normal puberty. Therefore, we have assessed the responses of normal boys at various stages of pubertal development to a single dose of the GnRH agonist nafarelin. Baseline LH, FSH, testosterone (T), estradiol (E2), and steroid intermediates, including 17 hydroxyprogesterone, increased during puberty. LH responses peaked at 3 h in prepubertal (P1; n = 8) and midpubertal (P2; n = 4) boys, at 12 h in late pubertal (P3; n = 8) boys, but earlier (0.5-1 h) in adults (P4; n = 10). LH levels remained high for 24 h in P3-P4. Indexes of both the readily releasable and reserve pools of pituitary LH increased significantly with advancing pubertal stage (P < 0.003). FSH responses differed among groups only at 24 h. Nafarelin stimulated T significantly in groups P2 < P3 < P4. The maximal responses of T were 0.54 +/- 0.25 (+/- SEM), 8.7 +/- 2.9, 18.5 +/- 1.0, and 15.3 +/- 1.4 nmol/L in these respective groups (by analysis of variance, F = 40.5; P < 0.001). However, nafarelin did not stimulate E2 significantly until late puberty; the maximal E2 responses to nafarelin treatment were 17.9 +/- 5.9, 26.7 +/- 8.7, 318 +/- 71.3, and 329 +/- 17.4 pmol/L in P1, P2, P3, and P4 (F = 18.3; P < 0.001). In contrast to E2, most intermediate steroids measured increased significantly in response to nafarelin in stages P2-P4. We conclude that a single dose of the GnRH agonist nafarelin stimulates gonadotropin secretion in normal prepubertal and pubertal males; it also stimulates gonadal steroid production in pubertal males. Pubertal maturation of gonadotrope function appears to involve mainly increases in both the readily releasable and reserve pools of LH. The findings that late pubertal boys had LH responses similar to those of men, but greater T and lesser 17-hydroxyprogesterone outputs are compatible with their pituitary-testicular axis operating at a less down-regulated state than that of adults. The apparently isolated failure of E2 to increase in response to nafarelin in early puberty suggests that maturation of aromatase activity normally does not become appreciable until late puberty. These findings suggest that a single dose of GnRH agonist may provide a simple means of assessing the maturation of the neuroendocrine-testicular axis. PMID- 8200937 TI - Characterization of regional and gender differences in glucocorticoid receptors and lipoprotein lipase activity in human adipose tissue. AB - Glucocorticoid receptor (GR) status was studied in adipose tissue from omental and sc abdominal adipose tissue. As the effects of glucocorticoids may be due to alteration of triglyceride uptake in adipose tissue, the activity of the enzyme lipoprotein lipase (LPL) was also investigated. Fat biopsies were obtained from 8 women and 11 men matched for age and body mass index. Omental adipose tissue contained 4 times the number of GR as sc abdominal adipose tissue (42.0 +/- 4.1 vs. 10.5 +/- 2.3 fmol/mg protein, respectively; P < 0.001) with similar Kd values. No gender difference in GR number was observed in adipose tissue from the two regions. LPL activity in omental adipose tissue was about 820 nmol FFA/h.g wet wt in both sexes, whereas LPL activity in sc adipose tissue was about 2- to 4 fold lower. Moreover, LPL activity in sc adipose showed marked gender differences, with 2-fold higher activity in women than in men (474 +/- 84 vs. 238 +/- 35 nmol FFA/h.g wet weight; P < 0.03). Finally, there was no correlation between GR number and LPL activity when each fat depot was investigated separately. However, a positive correlation between LPL activity and glucocorticoid binding was found when the data from both regions were pooled (r = 0.55; P < 0.01). In conclusion, human adipose tissue dexamethasone binding was higher in omental than in sc adipose tissue, without any gender difference. LPL activity was also higher in omental than in sc adipose tissue in both groups, without any gender difference. On the other hand, sc LPL activity was higher in females than in men. A correlation (positive) between GR number and LPL activity was only found when the data from both regions were pooled. PMID- 8200938 TI - Comparison of second and third generation methods for measurement of serum thyrotropin in patients with overt hyperthyroidism, patients receiving thyroxine therapy, and those with nonthyroidal illness. AB - We compared serum TSH results determined in second and third generation assays in patients with thyroid disease and nonthyroidal illnesses (NTIs) to evaluate the usefulness of the more sensitive assay. We studied 19 subjects with untreated hyperthyroidism, 12 hyperthyroid subjects sampled at 4-week intervals after beginning carbimazole, 153 subjects receiving T4 replacement, and 300 hospital in patients with a variety of NTIs. Serum TSH was measured, using a second generation immunometric method, together with free T4 and free T3. Samples with subnormal TSH (< 0.5 mU/L) were reassayed, using a more sensitive chemiluminescent immunometric method. Both assays revealed undetectable serum TSH levels in 18 of 19 overtly hyperthyroid patients. Undetectable TSH values (in both assays) were found in 30 of 33 patients with low serum TSH levels who were receiving treatment for hyperthyroidism, in association with normal thyroid hormone levels in 11. Undetectable TSH was evident in both patients receiving T4 and those with NTI, but use of the more sensitive assay led to a reduction in the number of subjects with undetectable TSH compared with the second generation results (T4-treated, 55 vs. 77 cases; NTI, 13 vs. 19 cases). There was a significant correlation between serum TSH and free T4 in the whole group on T4 (P < 0.001) and in those receiving T4 with low TSH (r = -0.33; P < 0.05); no significant correlation was evident in subjects with low serum TSH levels associated with NTI. An improvement in assay sensitivity led to a reduction in the number of patients being treated with T4 or with NTI in whom serum TSH was undetectable and, hence, an increase in those in whom overt hyperthyroidism could be excluded. Undetectable TSH results, even in a third generation assay, are not diagnostic of overt hyperthyroidism, but are also found in subjects with treated thyroid disease and NTI. PMID- 8200939 TI - Stimulation by peptide histidine methionine (PHM) of adrenocorticotropin secretion in patients with Cushing's disease: a comparison with the effect of vasoactive intestinal peptide (VIP) and a study on the effect of combined administration of corticotropin-releasing hormone with PHM or VIP. AB - The effect of peptide histidine methionine (PHM) on ACTH and cortisol secretion was examined in 12 female patients with Cushing's disease and 8 normal women. For comparison, we examined in both groups the effects of vasoactive intestinal peptide (VIP), human (h) CRH plus PHM, and hCRH plus VIP. Each peptide was given as an i.v. bolus in a dose of 100 micrograms, and plasma levels of ACTH and cortisol were measured before and at intervals up to 120 min after the injection. In all normal subjects, hCRH induced significant rises in ACTH (> 50% above the basal) and cortisol (> 20% above the basal), but PHM and VIP were without effect. In this group, hormonal responses after hCRH plus PHM and hCRH plus VIP were statistically indistinguishable from those after hCRH alone. Of the patients with Cushing's disease, 9 (75%) were responsive to hCRH, 5 (42%) were to VIP, and 3 (25%) were to PHM, showing significant increases in both ACTH and cortisol. All the 3 PHM responders were also responsive to VIP, and all the 5 VIP responders were also responsive to hCRH. Interestingly, the responders to VIP and PHM had higher ACTH and cortisol responses to hCRH compared with the nonresponders. In addition, in the patients with Cushing's disease the coadministration of hCRH with PHM or VIP produced additive increases in both ACTH and cortisol. These results suggest that PHM may be another hypothalamic hormone capable of paradoxically stimulating ACTH secretion in at least some patients with Cushing's disease. Although the ACTH-releasing action of PHM appears less potent than those of hCRH and VIP, the possibility was suggested that a certain common mechanism may operate in inducing the ACTH response to these 3 peptides. PMID- 8200940 TI - Nocturnal hyperparathyroidism: a frequent feature of X-linked hypophosphatemia. AB - Parathyroid function is described as normal in patients with phosphopenic rickets before initiation of therapy with phosphate salts; however, hyperparathyroidism is an occasional complication of treatment. We observed a higher than expected frequency of hyperparathyroidism in patients with phosphate-wasting rickets, present before treatment in some patients and, more frequently, after the onset of treatment. To better define parathyroid status in hypophosphatemic rickets, we sampled 12 affected children and 7 affected adults every 4 h for 1 day and measured PTH in assays detecting midmolecule fragments (cPTH) and intact hormone (iPTH). All children and 4 adults were receiving a vitamin D preparation and phosphate salts; 3 adults were untreated. Mean cPTH, iPTH, and nephrogenous cAMP excretions in each group of patients were greater than in controls. Exaggerated nocturnal rises in both cPTH and iPTH characterized the profile in patients. Seventeen patients demonstrated frankly elevated cPTH at night, with peak values at midnight, whereas no control individual did. Although mean iPTH values in patients increased at night, they did not exceed the upper limit of normal. Hyperparathyroidism in hypophosphatemic rickets occurs in both children and adults, may be present in untreated patients, is predominantly nocturnal, and is characterized by exaggerated secretion of midmolecule fragments. This manifestation of hypophosphatemic rickets is more widespread than currently recognized; we speculate that it may contribute to the pathogenesis of nephrocalcinosis and precede the development of tertiary hyperparathyroidism. PMID- 8200941 TI - Thyrotropin receptor antisera for the detection of immunoreactive protein species in retroocular fibroblasts obtained from patients with Graves' ophthalmopathy. AB - Autoimmunity against the TSH receptor (hTSH-R) is known to be the proximate cause of thyroidal activation in Graves' disease, but has not been definitively linked to extrathyroidal manifestations of this disorder, such as ophthalmopathy and pretibial myxedema. In an effort to increase our knowledge concerning mechanisms responsible for Graves' ophthalmopathy, we used antiserum directed against a highly immunogenic portion of the hTSH-R (amino acids 352-367; P1) to assess the presence of this receptor or immunologically related protein in cultured human retroocular fibroblasts obtained from patients with Graves' ophthalmopathy. Immunoenzymatic and immunofluorescent studies revealed specific staining of both cytoplasmic and cell membrane-associated protein in discrete vesicles. To further evaluate the immunoreactive species present in these cells, immunoblotting experiments were performed using hTSH-R-specific antisera (anti-P1) and sera obtained from patients with Graves' disease. Several protein bands were identified using both anti-P1 and Graves' disease patient sera, including species at mol wt of 95, 71, and 18 kilodaltons, the possible significance of which is discussed. The results support the hypothesis that immunity against the hTSH-R or related proteins contributes to the ophthalmopathy of Graves' disease. PMID- 8200942 TI - Response of fat cells to growth hormone (GH): effect of long term treatment with recombinant human GH in GH-deficient adults. AB - GH deficiency impairs lipid metabolism in adults, but little is known about the direct effect of GH on adipose tissue in humans. First, the in vitro response of fat cells to GH in five GH-deficient adults was studied; second, it was investigated whether 6-month recombinant human GH (rhGH) administration modifies this response. Biopsies of fat were obtained from the periumbilical region before and after rhGH administration. The response of the collagenase-isolated fat cells to various concentrations of GH was assessed by glycerol release, measured by bioluminescence. Before treatment, GH induced a lipolytic activity from the adipocytes, which became significantly higher after 6 months of treatment. Thus, this study provides evidence for an intrinsic lipolytic activity of GH in GH deficient adults and for its improvement after long term rhGH administration. PMID- 8200943 TI - Prostaglandin endoperoxide-H synthase (PGHS) activity and immunoreactive PGHS-1 and PGHS-2 levels in human amnion throughout gestation, at term, and during labor. AB - Prostaglandins (PGs) are of primary importance in the initiation and maintenance of labor in women. A major intrauterine source of prostaglandins is the amnion, which synthesizes increased amounts of PGE2 at term labor. Because PG endoperoxide-H synthase (PGHS) catalyzes the rate-limiting step of PG synthesis from arachidonic acid, we investigated the changes in amniotic PGHS specific activity during gestation and at term and preterm labor. Also, we determined the level of immunoreactive PGHS protein in the amnion to evaluate the mechanisms by which PGHS activity may be regulated. PGHS specific activity, measured at the amount of PGE2 produced by amnion microsomes under optimal conditions, was 18.2 +/- 3.7 pg PGE2/micrograms protein.min (mean +/- SE; n = 19) at term (37-42 weeks gestation) before the spontaneous onset of labor. PGHS specific activity was significantly higher after spontaneous term labor (38.9 +/- 6.0 pg PGE2/micrograms protein.min; n = 19; P < 0.05). Amnion samples from preterm (< 36 weeks gestation) nonlaboring patients contained low levels of PGHS specific activity (5.9 +/- 1.8 pg PGE2/micrograms protein.min; n = 9), which increased significantly with spontaneous preterm labor (28.3 +/- 6.8 pg PGE2/micrograms protein.min; n = 10; P < 0.05). Longitudinal analysis of the data showed that PGHS specific activity was low in the first and second trimesters of gestation, but increased dramatically before labor onset at term. We detected PGHS protein in all microsomal samples, with an antiovine PGHS antibody recognizing both PGHS 1 and -2 isoforms of the enzyme. However, there was no correlation between PGHS specific activity and the amount of immunoreactive PGHS protein. Using an antibody specific for PGHS-2, we detected immunoreactive protein in only 9 of the 25 tissues examined and found no correlation between PGHS specific activity and the amount of PGHS-2 protein. These results suggest that 1) PGHS specific activity in the amnion increases sharply before the onset of labor at term; 2) further increases in specific activity occur during term and preterm labor; and 3) the specific activity of PGHS in the amnion is not related directly to the amount of immunoreactive enzyme protein. PMID- 8200944 TI - Human growth hormone (hGH)-(44-191), a reportedly diabetogenic fragment of hGH, circulates in human blood: measurement by radioimmunoassay. AB - The purpose of these experiments was to determine whether a 17-kilodalton (K) fragment of human GH (hGH), hGH-(44-191), a peptide 10 times more potent than intact hGH in causing glucose intolerance in an animal model, circulates in human blood. Analysis of pituitary extracts and sera by Western blotting revealed the presence of a 17K hGH-immunoreactive band in both samples. Monoclonal antibodies to recombinant hGH-(44-191) cross-reacted with the 17K hGH-immunoreactive band of the pituitary. A RIA specific for hGH-(44-191) was developed using recombinant hGH-(44-191) as the tracer and standard, and a mouse anti-hGH-(44-191) serum as the source of antibody. The RIA detected hGH-(44-191) in human sera and pituitary extracts. The concentration of hGH-(44-191) in pituitary glands was 1/100th to 1/500th of the hGH concentration, but in serum its concentration averaged 1-2 times higher than that of hGH. Serum hGH-(44-191) concentrations were higher in pregnant than in nonpregnant women. The data document the existence of hGH-(44 191) in human pituitary gland and serum, and provide initial evidence that it may be physiologically produced. As its concentration is affected by the physiological state of the individual, it may play a role in the expression of the physiological and pathological actions of hGH. PMID- 8200945 TI - Paradoxical inhibition by aspirin of naloxone-induced adrenocorticotropin secretion in myotonic dystrophy. AB - The ACTH response to endogenous or exogenous CRH is increased in patients with myotonic dystrophy (DM), possibly because of abnormal function of cAMP-dependent protein kinases in this condition. Arachidonic acid (AA) metabolites are believed to interact with the cAMP-dependent second messenger system activated by CRH; therefore, drugs that interfere with AA metabolism may alter ACTH secretion in DM. In this study, seven DM patients were given naloxone, which stimulates endogenous CRH release, and aspirin, which inhibits the synthesis of prostaglandins from AA via the cyclooxygenase metabolic pathway. Pretreatment with aspirin reduced the mean integrated ACTH response to naloxone by 33% (P < 0.05). However, the corresponding 18% reduction in cortisol levels was not statistically significant (P > 0.10). These findings are in contrast to those of a previous study using an identical protocol, in which aspirin increased the ACTH response to naloxone in six normal volunteers. This difference between DM and control subjects is consistent with the hypothesis that the interaction between AA metabolites and the cAMP-dependent protein kinase-A second messenger system is abnormal in the corticotrophs of persons with DM. PMID- 8200946 TI - Bioactivity and metabolism of C-type natriuretic peptide in normal man. AB - C-Type natriuretic peptide (CNP) is a recently identified member of the natriuretic peptide family with potent vasodepressor activity in experimental animals. Specific CNP receptors and gene transcripts have been identified in human vascular tissues, but the bioactivity and metabolism of CNP in humans are unknown. Accordingly, we have studied the renal, hormonal, and hemodynamic responses in nine normal men (seated, nonfasting) receiving a morning infusion (2 h) of synthetic human CNP-22 (5 pmol/kg.min) or placebo in single blind, random order. To determine the vasodepressor action, the effect of a second identical (afternoon) infusion on the pressor and hormone responses to angiotensin-II (2, 4, and 8 ng/kg.min each for 30 min) was also studied. In the morning infusion, plasma CNP increased from undetectable baseline levels to plateau levels (mean, 60 +/- 6 pmol/L) at 30-120 min. The mean MCR was 4.8 +/- 0.7 L/min, and the t 1/2 (plasma) was 2.6 min. Compared with the effects of placebo, there were significant increases in plasma cGMP (P = 0.001) and plasma atrial natriuretic peptide (ANP; P = 0.02) and a significant decrease in plasma aldosterone (P = 0.007). No significant hemodynamic action or natriuresis was observed. During coinfusion of angiotensin-II, the expected pressor and aldosterone responses were not significantly altered by CNP. In contrast to atrial and brain natriuretic peptide, short term infusion of CNP in humans, achieving supraphysiological levels in plasma, are not vasodepressor or natriuretic. Increases in plasma ANP and plasma cGMP and inhibition of aldosterone may be due in part to competitive displacement by CNP of ANP in common degradative pathways. PMID- 8200947 TI - Parathyroid function in mild to moderate renal failure: evaluation by oral calcium suppression test. AB - Alterations of PTH secretion in patients with mild to moderate chronic renal failure were evaluated using an oral calcium suppression test. Ionized calcium and PTH were measured at 0, 30, 60, 120, and 180 min after ingestion of 2 g elemental calcium in 18 patients and 15 control subjects. The mean glomerular filtration rate was significantly lower in the patients compared to the controls (58 +/- 18 vs. 100 +/- 12 mL/min, P < 0.01) but the basal ionized calcium and PTH were not significantly different. After ingestion of calcium there was a similar rise in ionized calcium with time in both patients and controls. However the mean PTH concentration in the patients was significantly higher than the controls at all equivalent ionized calcium concentrations. Overall the patients showed significantly less percentage suppression of PTH compared to control subjects, 63 +/- 10% vs. 74 +/- 9%, P < 0.01. The minimum PTH value was also higher in the patients than the controls, 1.2 +/- 0.7 vs. 0.7 +/- 0.3 pmol/L, P < 0.01. Thus although the majority of patients had PTH levels within the conventional reference range they demonstrated abnormal suppression of PTH secretion. The data from this study would further support the view that treatment for secondary hyperparathyroidism should be started early on in the course of chronic renal failure. PMID- 8200948 TI - Circulating growth hormone isoforms in girls with Turner's syndrome. AB - To evaluate the presence of different GH isoforms in serum of girls with Turner's syndrome, we measured the serum GH content using RIAs with three different site specific monoclonal antibodies (MAbs). We compared the results to those obtained with authentic GH and GH isoforms. Compared to pituitary GH (mol wt, 22K daltons) as the standard for all three MAbs, serum from girls with Turner's syndrome did not displace tracer [125I]GH equally with all three MAbs. The relative amounts of GH-immunoreactive material found in Turner's syndrome were different from the amounts observed in normal adults and most children with idiopathic short stature. The presence of GH, other than 22K GH, in serum from girls with Turner's syndrome was confirmed by affinity chromatography. The existence of different isoforms of GH, as shown by different cross-reactivity patterns with different MAbs to GH, may explain the conflicting results reported for GH secretion in girls with Turner's syndrome. PMID- 8200949 TI - Dose-dependent catch-up growth after 2 years of growth hormone treatment in intrauterine growth-retarded children. Belgian and French Pediatric Clinics and Sanofi-Choay (France). AB - This study reports the results of a 2-yr clinical trial with GH in 95 short prepubertal children with non-GH-deficient intrauterine growth retardation. This randomized, double blind, controlled study compared the effects of placebo (restricted to the first 6 months) and two doses of GH (0.4 and 1.2 IU/kg.week) given sc 6 days/week for 2 yr. A significant GH dose-dependent growth acceleration was observed. Mean height gain (SDS/CA) was 0.66 +/- 0.07 in group I (low dose, 0.4 IU/kg.week) compared to 1.25 +/- 0.07 in group II (high dose, 1.2 IU/kg.week). Mean bone maturation progression (expressed in months) was 26.2 +/- 1.7 and 30.2 +/- 1.5 over 24 months in groups I and II, respectively. Onset of puberty was observed in some patients of both groups. Whether chronic use of a high GH dose will advance the onset of puberty remains to be established. A great variability of growth acceleration was seen among GH dose groups, suggesting that factors in addition to GH dose might modulate individual responses to treatment. In conclusion, it is suggested that in these patients, dose-dependent catch-up growth could be induced by GH treatment. PMID- 8200950 TI - Genetic influences on type I collagen synthesis and degradation: further evidence for genetic regulation of bone turnover. AB - Circulating osteocalcin, a marker of bone formation, is under strong genetic influence, and this effect is related to the genetic influence on bone density. To examine genetic influences on bone turnover further, other markers of bone formation (serum carboxyterminal propeptide of type I procollagen, PICP), bone resorption (serum pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, ICTP), and nonosseous connective tissue synthesis (serum aminoterminal propeptide of type III procollagen, PIIINP) were studied in 82 female twin pairs: 42 monozygotic (MZ) and 40 dizygotic (DZ) twin pairs (mean age, MZ; 48.4 yr; DZ; 45.6 yr). The intraclass correlation coefficients of MZ twin pairs, rMZ, for serum PICP (0.78) and serum ICTP (0.68) were significantly greater than the corresponding rDZ (0.31 and 0.36, respectively), but a genetic effect on serum PIIINP was not demonstrable. Within DZ twin pair differences in serum PICP predicted differences in lumbar spine bone density (r = -0.37); higher serum PICP levels indicating the twin with the lower lumbar spine bone density. Also within pair differences in serum ICTP and PICP predicted differences in bone density at the lumbar spine independent of serum osteocalcin. These data indicate that both synthesis and degradation of type I collagen are genetically determined and that this phenomenon is related to the genetic regulation of bone density. PMID- 8200951 TI - Ovarian steroid-modulated stromelysin-1 expression in human endometrial stromal and decidual cells. AB - This study examined steroid-regulated expression of the metalloproteinase stromelysin-1 in primary human endometrial stromal and decidual cells. Immunoblot analysis using a specific polyclonal antibody against stromelysin-1 revealed that the progestin medroxyprogesterone acetate (MPA) produced a time-dependent reduction in a band at 50,000 mol wt. Although the cells were refractory to estradiol (E2) alone, E2 plus MPA further reduced the intensity of this stromelysin-1 zone. By 6 days of incubation, MPA inhibited levels of secreted stromelysin-1 by one third, and E2 plus MPA inhibited stromelysin-1 levels by two thirds compared with the control values. This differential responsiveness of the stromal cells to the two steroids is reported for several biochemical end points of decidualization. Northern analysis indicated pronounced inhibition of stromelysin-1 messenger ribonucleic acid (mRNA) by E2 plus MPA over a concentration range that simulated circulating progesterone levels of the luteal phase (10(-8) mol/L) through pregnancy (10(-6) mol/L). After suppression of stromelysin-1 expression in the stromal cell monolayers by E2 plus MPA, steroid withdrawal led to a several-fold enhancement of stromelysin-1 mRNA by 4 days and of the stromelysin-1 protein by 7 days. Given its actions in degrading several extracellular matrix components and activating other MMP zymogens, steroid withdrawal-enhanced stromelysin-1 activity could mediate a proteolytic cascade that promotes the rapid tissue destruction and vascular disruption associated with menstruation. Stromelysin-1 expression by cultured decidual cells isolated from first trimester endometrium was also reduced by MPA and synergistically reduced by E2 plus MPA. As activation of the 92-kilodalton gelatinase/type IV collagenase, a crucial mediator of trophoblast invasiveness, is stromelysin-1 dependent, reduced decidual stromelysin-1 production could help to limit trophoblast invasion. PMID- 8200952 TI - Expression of the growth hormone receptor gene in human digestive tissue. AB - We have examined the forms and the distribution of the messenger ribonucleic acids (mRNAs) encoding the GH receptor (GHR) in human digestive tissues. GHR mRNAs were identified and characterized by Northern blot, dot blot, and in situ hybridization analyses, using complementary DNAs coding for the extracellular part of the human liver GHR. Amplification using the polymerase chain reaction was also used, as tissues express low levels of GHR mRNAs. Our results demonstrate that the GHR gene is expressed in human liver, pancreas, esophagus, stomach, small intestine, and colon. A single 4.5-kilobase mRNA form, which probably encodes the full-length membrane receptor, was detected. GHR mRNA was visualized by in situ hybridization in hepatocytes, exocrine pancreas, and some islet cells; signal was also present in the mucosa of the digestive tract. No specific GH-binding-protein mRNA was found, suggesting that in man, the soluble form of the receptor is generated through proteolytic cleavage of the membrane receptor. PMID- 8200953 TI - In vivo dihydrotachysterol2 metabolism in normal man: 1 alpha- and 1 beta hydroxylation of 25-hydroxydihydrotachysterol2 and effects on plasma parathyroid hormone and 1 alpha,25-dihydroxyvitamin D3 concentrations. AB - It has recently been shown that in the rat, dihydrotachysterol (DHT) is extensively metabolized in the side-chain in vivo along pathways similar to those of vitamin D. In addition 25-hydroxy-DHT2 [25OHDHT2] is hydroxylated at C1, producing both 1 alpha- and 1 beta- hydroxy compounds. An in vivo study in 1988 demonstrated that in normal adult subjects receiving oral DHT2, plasma 1 alpha,25 dihydroxyvitamin D [1,25-(OH)2D] concentrations fell, but with unchanged plasma PTH levels. Down-regulation of 1,25-(OH)2D3 production by 25-(OH)DHT2 or some other unknown metabolite was also suggested as an explanation for these observations. To investigate whether either of the newly characterized 1 alpha,25 or 1 beta,25-(OH)2DHT2 was formed in vivo in normal man, DHT2 (approximately 1 mg/day, orally) was administered to healthy volunteers (three males and one female). Plasma was analyzed by high performance liquid chromatography and gas chromatography-mass spectrometry, demonstrating the formation of both 1 alpha,25- and 1 beta,25-(OH)2DHT2 in vivo in normal human subjects. Plasma levels of 1,25 (OH)2D3, PTH, ionized and total calcium, inorganic phosphate, and alkaline phosphatase were monitored. The plasma concentrations of DHT2, 25OHDHT2, and 1 alpha,25- and 1 beta,25-(OH)2DHT2 were measured by gas chromatography-mass spectrometry. In all volunteers, plasma ionized calcium increased slightly during DHT2 administration; 1,25-(OH)2D3 and PTH concentrations fell. Plasma levels of DHT2 and its metabolites rose over the same period. The average fall in the level of plasma 1,25-(OH)2D (60-70 pmol/L) was mirrored by a rise in the concentration of 1 alpha,25-(OH)2DHT2 (550 pmol/L). This ratio is appropriate, because it has previously been shown that in a reconstituted COS cell, 1 alpha,25-(OH)2DHT3 has roughly one tenth the potency of 1,25-(OH)2D3. At maximum concentration, the ratios of DHT2/25OHDHT2/1 beta,25-(OH)2DHT2/1 alpha,25-(OH)2DHT2 were approximately 10:1:2:0.1. The concentration of 1 beta,25-(OH)2DHT2 was greater than that of 25OHDHT2, and the ratio of 1 alpha,25- to 1 beta,25-(OH)2DHT2 (1:20) was substantially lower than that in rat plasma (3:10). The data presented here suggest that the active DHT2 metabolite in man is 1 alpha,25-(OH)2DHT2 and that the fall in plasma 1,25-(OH)2D seen during DHT therapy may be partly the result of suppressed PTH secretion. PMID- 8200954 TI - A 3,3'-diiodothyronine sulfate cross-reactive compound in serum from pregnant women. AB - Recently, we found high serum/urine concentrations of 3,3'-diiodothyronine sulfate (T2S) in both fetal and maternal sheep. In the present study, a RIA was employed to detect and measure serum T2S in women of different gestational ages and after delivery. Results were compared with values in nonpregnant women. In maternal serum, we identified a material that cross-reacts with T2S antibody, but is not T2S. Its concentration increased with the progression of pregnancy. The exact chemical structure of the T2S-like material (which we designated compound W) is unclear. It is immunologically (or chemically) similar to T2S, but does not cochromatograph with synthetic T2S in high pressure liquid chromatography. The serum concentrations of compound W were expressed as T2S equivalents (nanomoles per L +/- SE). Serum compound W concentrations were slightly elevated in women during the first trimester compared to those in nonpregnant women (0.73 +/- 0.04 vs. 0.17 +/- 0.02 nmol/L; P < 0.01). There was a moderate and progressive rise in the compound W concentration between 14-35 weeks gestation. The maternal serum compound W concentration then rapidly peaked before parturition (36-40 weeks gestation, 3.49 +/- 0.49 nmol/L; 27-35 weeks, 1.67 +/- 0.11 nmol/L; P < 0.01). After parturition, maternal serum levels of compound W decreased from 2.61 +/- 0.18 nmol/L (n = 25) to 1.47 +/- 0.12 nmol/L (n = 18) at 1 day, 0.89 +/- 0.07 nmol/L (n = 15) at 3 days, and 0.33 +/- 0.03 nmol/L (n = 8) at 7 days. hCG increased serum concentrations of T2S-cross-reactive material 6.2-fold (P < 0.01) in nonpregnant women. In summary, whereas hCG stimulation may account for some increase in maternal serum concentrations of this T2S-like material in the first trimester, the more rapid increase in maternal serum compound W concentrations during the late third trimester are probably related to changes that occur in fetal thyroid hormone economy. It is speculated that placental transfer and transformation of fetal T3 may be related to the rise in the level of T2S-like compound W in the serum of pregnant women. PMID- 8200955 TI - Changes in glucose turnover parameters and improvement of glucose oxidation after 4-week magnesium administration in elderly noninsulin-dependent (type II) diabetic patients. AB - The aim of the present study was to investigate the effects of magnesium supplementation on glucose uptake and substrate oxidation in noninsulin-dependent (type II) diabetic patients. Nine elderly non-obese noninsulin-dependent (type II) diabetic patients, treated by diet only, participated in the study, which was designed as randomized, double blind, and cross-over. Each patient was followed up for a prestudy period of 3 weeks before inviting him/her to receive placebo or magnesium supplementation (15.8 mmol/day) for 4 weeks. At the end of each treatment period, a euglycemic hyperinsulinemic glucose clamp with simultaneous D [3-3H]glucose infusion and indirect calorimetry was performed. Magnesium supplementation resulted in significantly increased plasma and erythrocyte magnesium levels, whereas body weight and fasting plasma glucose did not change. In the last 60 min of the glucose clamp, insulin-mediated glucose disappearance, total body glucose disposal (24.5 +/- 0.4 vs. 28.2 +/- 0.7 mumol/kg.min; P < 0.005), and glucose oxidation (13.0 +/- 0.4 vs. 16.3 +/- 0.8 mumol/kg.min; P < 0.01) were increased after chronic magnesium supplementation. Endogenous glucose production, nonoxidative glucose disposal, lipid and protein oxidation, and insulin MCR were not affected. In conclusion, a 4-week magnesium supplementation improves insulin sensitivity and glucose oxidation in the course of a euglycemic hyperinsulinemic glucose clamp in noninsulin-dependent diabetic patients. Long term studies are needed to determine whether magnesium supplementation is useful in the management of type II diabetes. PMID- 8200957 TI - The tissue distribution of activin beta A- and beta B-subunit and follistatin messenger ribonucleic acids suggests multiple sites of action for the activin follistatin system during human development. AB - Activins have potent effects on early morphogenetic events during amphibian embryogenesis but no evidence for their role during human development other than their expression in steroidogenic tissues has been reported. We previously showed the expression of the activin type II and IIB receptor mRNAs in several tissues of the mid-gestational human fetus with highest expression levels in developing neural, muscular and exocrine glandular organs. We now report that the mRNA transcripts for activin beta A- and beta B-subunits and for the activin-binding protein follistatin are found co-expressed in several of these extragonadal tissues. Their mRNAs were detected by Northern analyses using specific single stranded 32P-labeled cDNA probes. In the nervous system, both activin beta A- and beta B-subunit transcripts were expressed in the cerebrum and spinal cord. Follistatin was abundantly expressed in the spinal cord whereas weaker signals where observed in the cerebrum and cerebellum. In the muscular system, beta A subunit was abundantly expressed in the heart but to a lesser extent in the skeletal muscle while the opposite was observed for follistatin. Follistatin, and activin beta A- and beta B-subunit mRNAs were also detected in developing kidney, salivary gland, liver, and adrenal. The predominance of beta A-subunit mRNAs in the bone marrow and beta B-subunit mRNAs in the salivary gland suggests specific roles for activin A and B, respectively, in these tissues. No hybridization signal was detected for the inhibin alpha-subunit in non-steroidogenic tissues indicating that, in contrast to activins and follistatin, the effects of inhibins may be restricted to the gonads and adrenals which are known to express high levels of the alpha-subunit transcript. Taken together, our results suggest that the activin-follistatin system regulates the development of several organ systems in the mid-gestational human fetus. PMID- 8200956 TI - Visceral fat accumulation in relation to sex hormones in obese men and women undergoing weight loss therapy. AB - In 70 healthy obese subjects (37 men and 33 premenopausal women; aged 27-51 yr; body mass index, 28-38 kg/m2), associations between the initial amount of visceral fat and sex hormone levels were studied as well as between changes that occurred in response to a 4.2 mJ/day deficit diet for 13 weeks. Magnetic resonance imaging was used to quantify the visceral fat depot. In women, an abundance of visceral fat was significantly associated with diminished levels of sex hormone-binding globulin and free 17 beta-estradiol/free testosterone (T) ratio and to elevated levels of free T after adjustment for age and total fat mass. In men, no significant relationships could be found between visceral fat accumulation and any of the sex hormones. Mean total fat loss was 11.3 +/- 3.3 (+/- SD) kg. In women, loss of visceral fat was significantly related to rises in the sex hormone-binding globulin level and the free 17 beta-estradiol/free T ratio independent of total fat loss, whereas in men, only the association between visceral fat loss and increased estrone level reached statistical significance. In conclusion, in obese premenopausal women, visceral fat predominance seems to be related to a relatively increased androgenicity. In obese men, sex steroid levels appear not to depend on the amount of visceral fat. In obese women, but not in obese men, visceral fat loss seems to be accompanied by a relative reduction in androgenicity. PMID- 8200958 TI - Low intelligence but not attention deficit hyperactivity disorder is associated with resistance to thyroid hormone caused by mutation R316H in the thyroid hormone receptor beta gene. AB - Resistance to thyroid hormone (RTH) is a syndrome of reduced responsiveness of tissues to thyroid hormone. The clinical manifestations are variable and 46-50% of children with RTH have attention deficit hyperactivity disorder (ADD). We present a new family with RTH (F120) found to have a mutation R316H in the thyroid hormone receptor beta (TR beta) gene identical for that reported in an unrelated family. Assignment of the mutant allele and haplotyping based on CA repeat polymorphism were done on 16 family members. Semistructured diagnostic interviews and psychometric testing were used to determine the psychiatric diagnosis of 12 family members by examiners blinded to the genotype. Three subjects were identified to have the R316H allele as well as mildly elevated free T4 index (168 +/- 12; normal range 77-135) and nonsuppressed TSH (4.1 +/- 1.7 mU/L). Only 2 of the subjects with RTH were found to have ADD, while one family member homozygous for the wild type TR beta and normal thyroid function tests also had ADD. Unaffected family members had higher full scale intelligence quotients (IQ) (93 +/- 7) than any of the 3 family members with RTH (77 +/- 5, p = 0.006). These data do not support the genetic linkage of ADD and RTH, but do suggest that RTH is associated with lower IQ scores that may confer a high likelihood of exhibiting ADD symptoms. PMID- 8200959 TI - Type 2 11 beta-hydroxysteroid dehydrogenase in human fetal tissues. AB - 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyzes the conversion of active cortisol to inactive cortisone, and regulates the access of cortisol to both the mineralocorticoid and glucocorticoid receptors. Two isoforms of 11 beta HSD have been described, the cloned "type 1" NADP(H)-dependent dehydrogenase/oxo reductase and a high affinity NAD-dependent dehydrogenase (type 2). In the fetus, 11 beta-HSD activity may serve to protect developing tissues from cortisol excess or may modulate the permissive actions of glucocorticoids. We have studied 11 beta-HSD activity and mRNA levels in human mid-gestational fetal tissues. Tissue homogenates were incubated with either 0.1 mumol/L cortisol and 400 mumol/L NAD, 2.5 mumol/L cortisol and 400 mumol/L NADP, or 0.1 mumol/L cortisone wither either 400 mumol/L NADPH or NADH. No activity (< 2.5% conversion) was observed in fetal tissues using either cortisone or 2.5 mumol/L cortisol as a substrate. 11-oxo reductase activity was observed in maternally-derived decidua. In keeping with these activity studies, northern blot analysis of fetal tissue RNA and PCR reverse transcriptase of type 1 11 beta-HSD mRNA indicated 11 beta-HSD mRNA in decidua, but failed to detect any type 1 11 beta-HSD mRNA transcripts in fetal tissues. In contrast when 0.1 mumol/L cortisol was used as a substrate in the presence of NAD, 11 beta-HSD activity was ubiquitous with highest levels seen in the kidney (131 +/- 16 (SE) pmoles cortisone formed/h/mg.protein) > lung > gonad > liver > colon. 11 beta-HSD activity in fetal tissues is mediated by the type 2, high affinity, isoform. The widespread distribution of this novel isoform suggests that it may play an important role in fetal development. Type 1 11 beta HSD mRNA and activity are absent in mid-gestational fetal tissues, but present in maternally-derived decidua, suggesting that its ontogeny is a late-gestational of post-natal event. PMID- 8200960 TI - The wanderings of a platelet gene: what is "neo" Ib beta telling us? PMID- 8200961 TI - Renal contribution to glucose production after a brief fast: fact or fancy? PMID- 8200962 TI - Signaling by nonreceptor surface-mediated redox-active biomolecules. PMID- 8200963 TI - Paroxysmal nocturnal hemoglobinuria and the glycosylphosphatidylinositol anchor. PMID- 8200964 TI - Inhibition of bone resorption in vitro by antisense RNA and DNA molecules targeted against carbonic anhydrase II or two subunits of vacuolar H(+)-ATPase. AB - The bone resorbing cells, osteoclasts, express high levels of carbonic anhydrase II (CA II) and vacuolar H(+)-ATPase (V-ATPase) during bone resorption. We have used antisense RNA and DNA molecules targeted against CA II, and against 16- and 60-kD subunits of vacuolar H(+)-ATPase (V-ATPase), to block the expression of these proteins in vitro. Osteoclastic bone resorption was studied in two in vitro culture systems: release of 45Calcium from prelabeled newborn mouse calvaria cultures, and resorption pit assays performed with rat osteoclasts cultured on bovine bone slices. Both antisense RNA and DNA against CA II and the V-ATPase were used to compare their specificities as regards inhibiting bone resorption in vitro. The antisense molecules inhibited the synthesis of these proteins by decreasing the amounts of mRNA in the cells in a highly specific manner. In osteoclast cultures treated with the 16-kD V-ATPase antisense RNA, acidification of an unknown population of intracellular vesicles was highly stimulated. The acidification of these vesicles was not sensitive to amiloride or bafilomycin A1. This suggests the existence of a back-up system for acidification of intracellular vesicles, when the expression of the V-ATPase is blocked. Our results further indicate that blocking the expression of CA II and V-ATPase with antisense RNA or DNA leads to decreased bone resorption. PMID- 8200965 TI - Expression and localization of human oxytocin receptor mRNA and its protein in chorion and decidua during parturition. AB - Oxytocin (OT) is widely used to induce labor in the clinical setting. However, its physiological role in normal human parturition remains unclear. We demonstrated the enhanced expression of OT receptor (OTR) mRNA in chorio-decidual tissue, using the polymerase chain reaction after the reverse transcriptase reaction (RT-PCR) and Northern blot analysis. OTR gene expression in chorio decidual tissue increased fivefold during the course of parturition. In situ hybridization of fetal membrane revealed the expression of OTR mRNA in maternally derived decidual cells. The OTR mRNA was also detected in fetally derived chorionic trophoblast cells. Immunohistochemistry, using a newly developed anti OTR monoclonal antibody, demonstrated the distribution of OTR protein in fetal membrane. The distribution pattern of OTR protein and OTR mRNA was identical, indicating that the regulation of OTR expression occurs mainly at the transcriptional level. These results support the idea that the expression of decidual OTR regulates the initiation and amplification of labor. The implications of these findings with regard to the pathogenesis of preterm labor are also discussed. PMID- 8200966 TI - Enzyme replacement therapy for murine mucopolysaccharidosis type VII. AB - Recombinant mouse beta-glucuronidase administered intravenously to newborn mice with mucopolysaccharidosis type VII (MPS VII) is rapidly cleared from the circulation and localized in many tissues. Here we determine the tissue distribution of injected enzyme and describe its effects on the histopathology in 6-wk-old MPS VII mice that received either one injection of 28,000 U recombinant beta-glucuronidase at 5 wk of age or received six injections of 28,000 U given at weekly intervals beginning at birth. These mice were compared with untreated 6-wk old MPS VII mice. The single injection decreased lysosomal distention in the fixed tissue macrophage system. MPS VII mice that received multiple injections had 27.8, 3.5, and 3.3% of normal levels of beta-glucuronidase in liver, spleen, and kidney, respectively. Brain had detectable beta-glucuronidase, ranging from 2.0-12.1% of normal. Secondary elevations of alpha-galactosidase and beta hexosaminidase in brain, spleen, liver, and kidney were decreased compared with untreated MPS VII mice. Although no improvement was observed in chondrocytes, glia, and some neurons, the skeleton had less clinical and pathological evidence of disease and the brain had reduced lysosomal storage in meninges and selected neuronal groups. These data show that recombinant beta-glucuronidase treatment begun in newborn MPS VII mice provides enzyme to most tissues and significantly reduces or prevents the accumulation of lysosomal storage during the first 6 wk of life. Whether therapy begun later in life can achieve this level of correction remains to be established. PMID- 8200967 TI - Gonadotropin-releasing hormone receptor mRNA expression by human pituitary tumors in vitro. AB - An important question in the pathogenesis and regulation of human gonadotroph adenomas is whether heterogeneous gonadotropin responses to gonadotropin releasing hormone (GnRH) are due to dysregulation of GnRH receptor biosynthesis and/or cell-signaling pathways. We investigated gonadotropin responsiveness to pulsatile GnRH in 13 gonadotroph adenomas. All tumors had evidence of follicle stimulating hormone (FSH) beta and alpha subunit biosynthesis using reverse transcriptase/polymerase chain reaction (RTPCR) techniques. Four tumors significantly increased gonadotropin and/or free subunit secretion during pulsatile 10(-8) M GnRH administration. The GnRH antagonist Antide (10(-6) to 10( 8) M) blocked secretory increases in all GnRH-responsive tumors. Gonadotropin and/or free subunit secretion increased after 60 mM KCl, confirming that GnRH nonresponsiveness was not due to intracellular gonadotropin depletion. We hypothesized that GnRH nonresponsiveness in these tumors may be due to GnRH receptor (GnRH-Rc) biosynthetic defects. RTPCR analyses detected GnRH-Rc transcripts only in responsive tumors and normal human pituitary. This is the first demonstration of a cell-surface receptor biosynthetic defect in human pituitary tumors. We conclude (a) one third of gonadotroph tumors respond to pulsatile GnRH in vitro, (b) GnRH-Rc mRNA is detected in human gonadotroph adenomas and predicts GnRH responsiveness, and (c) GnRH-Rc biosynthetic defects may underlie GnRH nonresponsiveness in gonadotroph tumors. PMID- 8200968 TI - Interleukin-6 attenuates agonist-mediated calcium mobilization in murine osteoblastic cells. AB - Interleukin-6 (IL-6) is a multifunctional cytokine which is made by osteoblasts and has diverse effects on bone metabolism. We studied the interaction of IL-6 with the Ca2+ and cAMP signaling systems in the osteoblastic cell line UMR-106 and in primary osteoblastic cultures derived from neonatal rat calvariae. IL-6 did not alter basal intracellular calcium concentration ([Ca2+]i) but inhibited Ca2+ transients induced by parathyroid hormone (PTH), prostaglandin E2 (PGE2), and endothelin-1 in both dose- (100-400 U/ml) and time- (4-48 h) dependent manners. The effect of the cytokine was abolished by the tyrosine kinase inhibitor, herbimycin A (50 ng/ml). The IL-6 effect on the Ca2+ message system was related to suppressed production of hormonally induced inositol 1,4,5 triphosphate and inhibition of Ca2+ release from intracellular stores. Hormonally induced calcium entry pathways (estimated by using Mn2+ as a surrogate for Ca2+) were not, however, altered by the cytokine. IL-6 did not modulate cAMP generation in osteoblasts. With respect to osteoblast function, IL-6, although having no effect on cell proliferation by itself, greatly enhanced the antiproliferative effect of PGE2 and PTH. Because the production of IL-6 in osteoblasts is stimulated by calciotropic hormones (e.g., PTH and PGE2), the suppressive effect of the cytokine on hormonally induced Ca2+ transients may serve as an autocrine/paracrine mechanism for modulating the effect of hormones on bone metabolism. PMID- 8200969 TI - Impaired insulin-induced sympathetic neural activation and vasodilation in skeletal muscle in obese humans. AB - The sympathetic nervous system is an important regulatory mechanism of both metabolic and cardiovascular function, and altered sympathetic activity may play a role in the etiology and/or complications of obesity. In lean subjects, insulin evokes sympathetic activation and vasodilation in skeletal muscle. In obese subjects such vasodilation is impaired and, in turn, may contribute to insulin resistance. To examine the relationship between sympathetic and vasodilatory responses in skeletal muscle to hyperinsulinemia, we simultaneously measured muscle sympathetic nerve activity (MSNA) and calf blood flow at basal and during a 2-h hyperinsulinemic (6 pmol/kg per min) euglycemic clamp in eight lean and eight obese subjects. The major findings of this study are twofold: obese subjects had a 2.2 times higher fasting rate of MSNA, and euglycemic hyperinsulinemia, which more than doubled MSNA and increased calf blood flow by roughly 30% in lean subjects, had only a minor vasodilatory and sympathoexcitatory effect in obese subjects. In contrast, two non-insulin sympathetic stimuli evoked comparably large increases in MSNA in lean and obese subjects. We conclude that insulin resistance in obese subjects is associated with increased fasting MSNA and a specific impairment of sympathetic neural responsiveness to physiological hyperinsulinemia in skeletal muscle tissue. PMID- 8200970 TI - Characterization of angiotensin II receptors in cultured adult rat cardiac fibroblasts. Coupling to signaling systems and gene expression. AB - Cardiac hypertrophy is largely due to cardiac fibroblast growth and increased synthesis of extracellular matrix. This study has investigated the contribution of the vasoactive hormone, angiotensin II, toward this hypertrophic process. We have demonstrated that cultures of adult rat cardiac fibroblasts express AT1 but not AT2 receptors for angiotensin II. The ability of angiotensin II to stimulate phosphoinositide catabolism and to elevate intracellular calcium concentrations in these cells was blocked by losartan, a specific AT1 receptor antagonist, but not by the AT2 receptor antagonist CGP 42112. Exposure of adult cardiac fibroblasts to angiotensin II resulted in the induction of several growth-related metabolic events including c-fos protooncogene expression and increased synthesis of DNA, RNA, and protein. Angiotensin II was also found to induce collagen type I, alpha 1 chain transcript expression in cardiac fibroblasts as well as the synthesis and secretion of collagen by these cells. The data demonstrate that angiotensin II, via AT1 receptors, can stimulate cardiac fibroblast growth and increase collagen synthesis in cardiac tissue. Thus, angiotensin II may contribute toward the development of cardiac hypertrophy in conditions of hypertension that are associated with elevated concentrations of angiotensin II. PMID- 8200972 TI - Mitogen-activated protein kinase and its activator are regulated by hypertonic stress in Madin-Darby canine kidney cells. AB - Madin-Darby canine kidney cells behave like the renal medulla and accumulate small organic solutes (osmolytes) in a hypertonic environment. The accumulation of osmolytes is primarily dependent on changes in gene expression of enzymes that synthesize osmolytes (sorbitol) or transporters that uptake them (myo-inositol, betaine, and taurine). The mechanism by which hypertonicity increases the transcription of these genes, however, remains unclear. Recently, it has been reported that yeast mitogen-activated protein (MAP) kinase and its activator, MAP kinase-kinase, are involved in osmosensing signal transduction and that mutants in these kinases fail to accumulate glycerol, a yeast osmolyte. No information is available in mammals regarding the role of MAP kinase in the cellular response to hypertonicity. We have examined whether MAP kinase and MAP kinase-kinase are regulated by extracellular osmolarity in Madin-Darby canine kidney cells. Both kinases were activated by hypertonic stress in a time- and osmolarity-dependent manner and reached their maximal activity within 10 min. Additionally, it was suggested that MAP kinase was activated in a protein kinase C-dependent manner. These results indicate that MAP kinase and MAP kinase-kinase(s) are regulated by extracellular osmolarity. PMID- 8200971 TI - Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation. AB - The cytokines IL-1 beta and TNF-alpha cause cachexia and hypermetabolism in animal models, but their role in human inflammation remains controversial. The relationship between in vitro cytokine production and metabolism was examined in 23 adults with RA and 23 healthy control subjects matched on age, sex, race, and weight. Body composition was measured by multicompartmental analysis of body cell mass, water, fat, and bone mass. Resting energy expenditure (REE) was measured by indirect calorimetry. Cytokine production by PBMC was measured by radioimmunoassay. Usual energy intake, physical activity, disability scores, medication use, and other confounders were also measured. Body cell mass was 13% lower (P < 0.00001), REE was 12% higher (P < 0.008), and physical activity was much lower (P < 0.001) in subjects with RA. Production of TNF-alpha was higher in RA than controls, both before and after stimulation with endotoxin (P < 0.05), while production of IL-1 beta was higher with endotoxin stimulation (P < 0.01). In multivariate analysis, cytokine production was directly associated with REE (P < 0.001) in patients but not in controls. While energy and protein intake were similar in the two groups and exceeded the Recommended Dietary Allowances, energy intake in subjects with RA was inversely associated with IL-1 beta production (P < 0.005). In this study we conclude that: loss of body cell mass is common in RA; cytokine production in RA is associated with altered energy metabolism and intake, despite a theoretically adequate diet; and TNF-alpha and IL-1 beta modulate energy metabolism and body composition in RA. PMID- 8200973 TI - High expression of genes for calcification-regulating proteins in human atherosclerotic plaques. AB - Calcification is common in atheromatous plaques and may contribute to plaque rupture and subsequent thrombosis. However, little is known about the mechanisms which regulate the calcification process. Using in situ hybridization and immunohistochemistry we show that two bone-associated proteins, osteopontin (OP) and matrix Gla protein (MGP), are highly expressed in human atheromatous plaques. High levels of OP mRNA and protein were found in association with necrotic lipid cores and areas of calcification. The predominant cell type in these areas was the macrophage-derived foam cell, although some smooth muscle cells could also be identified. MGP was expressed uniformly by smooth muscle cells in the normal media and at high levels in parts of the atheromatous intima. Highest levels of this matrix-associated protein were found in lipid-rich areas of the plaque. The pattern of expression of these two genes contrasted markedly with that of calponin and SM22 alpha, genes expressed predominantly by differentiated smooth muscle cells and whose expression was generally confined to the media of the vessel. The postulated function of OP and MGP as regulators of calcification in bone and the high levels and colocalization of both in atheromatous plaques suggest they have an important role in plaque pathogenesis and stability. PMID- 8200974 TI - Islet cell antibodies predict insulin-dependent diabetes in United States school age children as powerfully as in unaffected relatives. AB - Islet cell antibodies (ICA) in the sera of nondiabetic relatives of patients with insulin-dependent diabetes (IDD) are predictive of the disease, a finding that permits the design of intervention strategies to prevent it. However, 85% or more of patients with new onset IDD have no affected relative. We therefore screened 9,696 schoolchildren between the ages of 5 and 18 yr (mean age 10.7 yr) in Pasco County, Florida for ICA in three surveys during 1984/5, 1987/8, and 1990/1 and have followed them prospectively. Approximately 4,000 of these children have been followed for nearly 8 yr. ICA titers > or = 10 Juvenile Diabetes Foundation units on replicate tests were detected in 57 of the children (0.59%). 10 children have developed diabetes so far, and all had ICA detected beforehand. The likelihood of developing IDD among the ICA-positive children was compared with 2,959 age matched nondiabetic first degree relatives of IDD probands who were screened for ICA by our laboratory during the same time period and also followed prospectively. Of 103 (3.5%) ICA-positive relatives, 31 have developed IDD. Life table analysis reveals no statistically significant differences in the probability of developing IDD between the ICA-positive schoolchildren and ICA positive first degree relatives (P = 0.3). The estimated risk of developing IDD by 7 yr in the ICA-positive schoolchildren was 45% (95% confidence interval 15 74%) compared with 43% (confidence interval 22-63%) in the relatives. We conclude that ICA appear to be as predictive of IDD in low-risk schoolchildren as they are in high-risk relatives. These data suggest that it is feasible to predict IDD by screening a general population of schoolchildren for ICA and that those found to be positive could be considered, in addition to relatives, for intervention protocols to prevent the disease. PMID- 8200975 TI - Oxygen radicals inhibit human plasma acetylhydrolase, the enzyme that catabolizes platelet-activating factor. AB - Platelet-activating factor (PAF) can exert profound inflammatory effects at very low concentrations. In plasma, PAF is hydrolyzed to lyso-PAF by acetylhydrolase, an enzyme that circulates bound to LDL. Previous studies suggest that oxygen radicals may act synergistically with PAF to potentiate tissue injury. However, mechanisms underlying this interaction have not been elucidated. In this study we investigated whether oxygen radicals may inactivate PAF acetylhydrolase. PAF acetylhydrolase activity was measured in human plasma and purified LDL before and after exposure to radicals (10-20 nmol/min per ml) generated by xanthine/xanthine oxidase. Oxygen radicals induced > 50% loss of PAF acetylhydrolase activity within 60 s and almost complete inactivation by 10 min. This phenomenon was irreversible and independent of oxidative modification of LDL. Inactivation occurred without changes in the affinity constant of the enzyme (Km was 17.9 microM under control conditions and 15.1 microM after exposure to oxygen radicals). Inactivation was prevented by the scavengers superoxide dismutase or dimethylthiourea or by the iron chelator deferoxamine. Thus, superoxide-mediated, iron-catalyzed formation of hydroxyl radicals can rapidly and irreversibly inactivate PAF acetylhydrolase. Since concomitant production of PAF and oxygen radicals can occur in various forms of tissue injury, inactivation of acetylhydrolase might represent one mechanism by which oxygen radicals may potentiate and prolong the proinflammatory effects of PAF. PMID- 8200976 TI - Complementary DNA cloning of the alternatively expressed endothelial cell glycoprotein Ib beta (GPIb beta) and localization of the GPIb beta gene to chromosome 22. AB - Glycoprotein Ib beta (GPIb beta) exists in platelets disulfide-linked to glycoprotein Ib alpha (GPIb alpha), a major receptor for von Willebrand factor. Both GPIb alpha and GPIb beta are expressed in endothelial cells (EC). While the GPIb alpha mRNA and protein appear similar in platelets and EC, EC GPIb beta mRNA is larger than platelet GPIb beta and encodes a larger protein. We have cloned and sequenced EC GPIb beta cDNA and report a 2793-nucleotide sequence which contains a 411-amino acid open reading frame. The EC sequence contains all of the platelet cDNA sequence and all but three amino acids of the primary translation product. Like the genes encoding GPIb alpha, GPIX, and GPV, the GPIb beta gene appears simple in structure. Using human hamster hybrids, we have localized the GPIb beta gene to chromosome 22pter-->22q11.2. When we examined poly (A)+ RNA from several human tissues for GPIb beta mRNA expression, we found that GPIb beta mRNA was expressed in a variety of tissues but was most abundant in heart and brain, while GPIb alpha and GPIX mRNA expression was found only in lung and placenta at very low levels. The broad distribution of GPIb beta mRNA suggests that it may be playing a role different than or additional to its function in platelets. PMID- 8200977 TI - Retinal signal transmission in Duchenne muscular dystrophy: evidence for dysfunction in the photoreceptor/depolarizing bipolar cell pathway. AB - There have been reports of abnormal retinal neurotransmission determined by electroretinography in boys with Duchenne and Becker muscular dystrophy. Dystrophin may play a role in transmitting signals between photoreceptors and the excitatory synapse of the ON-bipolar cell. These electroretinographic changes appeared to be limited to the rod ON-pathway but we felt there was also similar abnormality in the cone ON-pathway. We used long-duration stimuli to separate ON (depolarizing bipolar cell) and OFF (hyperpolarizing bipolar cell) contributions to the cone-dominated ERG to better understand how the retina functions in boys with Duchenne muscular dystrophy. We recorded the electroretinograms of 11 boys with Duchenne muscular dystrophy and found abnormal signal transmission at the level of the photoreceptor and ON-bipolar cell in both the rod and cone generated responses. The OFF-bipolar cell that responds to the offset of the stimulus continues to function normally. The results support our hypothesis that retinal dystrophin plays a role in receptor function or controlling ion channels at the level of the photoreceptor and depolarizing bipolar cell. PMID- 8200978 TI - Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells. AB - Angiotensin II (Ang II) has been implicated in the development of progressive glomerulosclerosis, but the precise mechanism of this effect remains unclear. In an experimental model, we have shown previously that TGF-beta plays a key role in glomerulosclerosis by stimulating extracellular matrix protein synthesis, increasing matrix protein receptors, and altering protease/protease-inhibitor balance, thereby inhibiting matrix degradation. We hypothesized that Ang II contributes to glomerulosclerosis through induction of TGF-beta. Ang II treatment of rat mesangial cells in culture increased TGF-beta and matrix components biglycan, fibronectin, and collagen type I at both the mRNA and protein levels in a time- and dose-dependent manner. Saralasin, a competitive inhibitor of Ang II, prevented the stimulation. Ang II also promoted conversion of latent TGF-beta to the biologically active form. Coincubation of mesangial cells with Ang II and neutralizing antibody to TGF-beta blocked the Ang II-induced increases in matrix protein expression. Continuous in vivo administration of Ang II to normal rats for 7 d resulted in 70% increases in glomerular mRNA for both TGF-beta and collagen type I. These results indicate that Ang II induces mesangial cell synthesis of matrix proteins and show that these effects are mediated by Ang II induction of TGF-beta expression. This mechanism may well contribute to glomerulosclerosis in vivo. PMID- 8200979 TI - Mechanisms of fatty acid-induced inhibition of glucose uptake. AB - Increased plasma FFA reduce insulin-stimulated glucose uptake. The mechanisms responsible for this inhibition, however, remain uncertain. It was the aim of this study to determine whether the FFA effect was dose dependent and to investigate its mechanism. We have examined in healthy volunteers (13 male/1 female) the effects of three steady state plasma FFA levels (approximately 50, approximately 550, approximately 750 microM) on rates of glucose uptake, glycolysis (both with 3-3H-glucose), glycogen synthesis (determined with two independent methods), carbohydrate (CHO) oxidation (by indirect calorimetry), hepatic glucose output, and nonoxidative glycolysis (glycolysis minus CHO oxidation) during euglycemic-hyperinsulinemic clamping. Increasing FFA concentration (from approximately 50 to approximately 750 microM) decreased glucose uptake in a dose-dependent fashion (from approximately 9 to approximately 4 mg/kg per min). The decrease was caused mainly (approximately 2/3) by a reduction in glycogen synthesis and to a lesser extent (approximately 1/3) by a reduction in CHO oxidation. We have identified two independent defects in glycogen synthesis. The first consisted of an impairment of muscle glycogen synthase activity. It required high FFA concentration (approximately 750 microM), was associated with an increase in glucose-6-phosphate, and developed after 4-6 h of fat infusion. The second defect, which preceded the glycogen synthase defect, was seen at medium (approximately 550 microM) FFA concentration, was associated with a decrease in muscle glucose-6-phosphate concentration, and was probably due to a reduction in glucose transport/phosphorylation. In addition, FFA and/or glycerol increased insulin-suppressed hepatic glucose output by approximately 50%. We concluded that fatty acids caused a dose-dependent inhibition of insulin stimulated glucose uptake (by decreasing glycogen synthesis and CHO oxidation) and that FFA and/or glycerol increased insulin-suppressed hepatic glucose output and thus caused insulin resistance at the peripheral and the hepatic level. PMID- 8200980 TI - Two subsets of HLA-DQA1 alleles mark phenotypic variation in levels of insulin autoantibodies in first degree relatives at risk for insulin-dependent diabetes. AB - Levels of insulin autoantibodies (IAA) vary among different first degree relatives of insulin-dependent diabetes mellitus patients, suggesting genetic regulation. We previously reported elevated IAA among DR4-positive at risk relatives. In this study, 72/82 at risk relatives were IAA positive, of whom 75% (54/72) carried DR4 versus 20% (2/10) of IAA-negative relatives (P = 0.0004). However, 69% (18/26) of DR4-negative relatives were IAA positive. Since DR4 did not account for all IAA positivity, we analyzed DQA1 and DQB1 alleles. Homozygosity for DQA1 alleles deriving from the evolutionary lineage 4 (*0401, *0501, *0601) was associated with low IAA levels, while lineage 1-3 alleles (*0101, *0102, *0103, *0201, *0301) correlated with higher levels. Most (93%, 65/70) relatives with lineage 1-3 alleles were IAA positive (mean = 360 +/- 63 SEM nU/ml). Only 7/12 relatives homozygous for lineage 4 alleles were IAA positive, with lower levels than relatives with lineage 1-3 alleles (mean = 55 +/ 15 SEM nU/ml, P < 0.0001; 7/12 vs 65/70, P = 0.004). The amino acid sequences of lineage 1-3 alleles uniquely share glutamic acid (E) and phenylalanine (F) at positions 40 and 51 (EF alleles). Lineage 4 alleles have glycine (G) and leucine (L) at those positions (GL alleles). 90% (65/72) of IAA-positive relatives had an EF allele, while only 75% (54/72) had DR4 (P = 0.01). Homozygosity for GL alleles (often DQA1 *0501 on DR3 haplotypes) correlated with little or no humoral response to insulin. Thus, HLA-DQB1 GL alleles, or other genes on haplotypes (e.g., DR3) that carry these DQA1 alleles, may confer recessive low responsiveness to insulin. PMID- 8200981 TI - Interactions between insulin and norepinephrine on blood pressure and insulin sensitivity. Studies in lean and obese men. AB - To explore the interactions between insulin action and norepinephrine (NE) on blood pressure and muscle vascular resistance, we studied seven lean (66 +/- 1 kg) sensitive and seven age-matched obese (96 +/- 3 kg) insulin-resistant men after an overnight fast. Both groups were normotensive; however, the obese exhibited higher basal blood pressure, 90.8 +/- 2.2 vs. 83.4 +/- 1.6 mmHg, P < 0.04. Each subject was studied on two separate days during either saline (S) infusion or a euglycemic hyperinsulinemic clamp (I) achieving insulin concentrations of approximately 70 microU/ml. After 180 min of either S or I, NE was infused systemically at rates of approximately 50, 75, and 100 pg/kg per min. Glucose uptake was measured in whole body ([3-3H]glucose) and in leg by the balance technique. The results indicate: (a) the NE/pressor dose-response curve was decreased (shifted to the right) during I in lean but not in obese subjects, (b) I enhanced NE metabolic clearance by 20% in lean but not in obese, (c) NE decreases leg vascular resistance more in lean than in obese, and (d) NE causes a approximately 20% increase in insulin-mediated glucose uptake in both groups. In conclusion, insulin resistance of obesity is associated with an apparent augmented NE pressor sensitivity and decreased NE metabolic clearance. Both of these mechanisms can potentially contribute to the higher incidence of hypertension in obese man. Insulin resistance is likely to be a predisposing but not sufficient factor in the pathogenesis of hypertension. Because the obese group exhibited higher basal blood pressure, it is possible that our results reflect this difference. Further studies will be required to clarify this issue. PMID- 8200982 TI - Dietary cholesterol and downregulation of cholesterol 7 alpha-hydroxylase and cholesterol absorption in African green monkeys. AB - In this study, hepatic production of bile acid was considered together with intestinal cholesterol absorption as potential regulatory sites responsive to dietary cholesterol. Sequential liver biopsies were taken from 45 feral African green monkeys studied during three different diet periods. Low-fat Monkey Chow was fed during the baseline period, a cholesterol and fat-enriched diet was then fed for 12 wk during period 2, and finally, after a washout period of 10 wk, three subgroups were fed low-, moderate-, and high-cholesterol diets for 12 mo during period 3. The percentage of cholesterol absorbed in the intestine was significantly lower when higher levels of cholesterol were fed; however, this percentage was significantly and positively correlated to plasma cholesterol concentration at each dietary cholesterol level. Hepatic free and esterified cholesterol content were significantly elevated by dietary cholesterol challenge and remained elevated even after 20 wk of low-cholesterol diets. Hepatic mRNA abundance for cholesterol 7 alpha-hydroxylase (C7H) was significantly lower (approximately 60%) when the high-cholesterol diet was fed, with the decrease being greater than that seen for low density lipoprotein (LDL) receptor mRNA. At the same time, hepatic mRNA abundance for apolipoprotein B and hepatic lipase were not diet sensitive. C7H activity was decreased to a similar extent by diet as was C7H mRNA, although the correlation between enzyme activity and mRNA abundance was only r = 0.5, suggesting that dietary regulation includes factors in addition to transcriptional regulation. Activity and mRNA abundance of C7H remained decreased when liver esterified cholesterol content was reduced to only a two- to three-fold elevation over baseline, at a time when plasma cholesterol and hepatic LDL receptor mRNA abundance had returned to baseline levels. These data on liver C7H, obtained in one of the few primate species predisposed to cholesterol gallstone formation, support the hypothesis that the liver may attempt to downregulate intestinal cholesterol absorption by decreasing bile acid production when increased amounts of absorbed dietary cholesterol reach the liver. Presumably this represents attempted downregulation of intestinal cholesterol absorption by limiting bile acid availability as a means to maintain hepatic cholesterol balance. PMID- 8200983 TI - In situ glucose uptake and glucokinase activity of pancreatic islets in diabetic and obese rodents. AB - The present study evaluated the involvement of glucose transport and phosphorylation in glucose-stimulated insulin release from pancreatic islets. Using quantitative histochemical techniques, we investigated basal islet glucose content, islet glucose uptake in situ during acute extreme experimental hyperglycemia, and islet glucokinase activity in several animal models of diabetes and obesity. The basal islet glucose content in anaesthetized diabetic or obese rodents was either the same or higher than that in their relevant controls. The rate of glucose uptake of islet tissue in these animals after an i.v. glucose injection was different. The db+/db+ mouse and the obese Zucker rat exhibited significantly reduced islet glucose uptake rates. RIP-cHras transgenic mice, BHE/cdb rats and partially pancreatectomized rats showed normal islet glucose uptake rates. The activity of islet glucokinase was increased to a different degree related to the blood glucose level. All five animal models of diabetes or obesity exhibited either a delay or a reduction of insulin release in response to supra maximal glucose stimulation. Our results indicate that the impairment of glucose-induced insulin release in diabetes is not consistently associated with a reduction of islet glucose uptake nor a change of glucokinase activity. PMID- 8200984 TI - Pertussis toxin treatment alters manganese superoxide dismutase activity in lung. Evidence for lung oxygen toxicity in air-breathing rats. AB - Exposure of rats to hyperoxia or to treatment with endotoxin, increases lung manganese superoxide dismutase (MnSOD) gene expression. However, the paths by which these environmental signals are transduced into enhanced MnSOD gene expression are unknown. We now provide evidence that heterotrimeric G proteins are involved in the hyperoxia-induced increase in lung MnSOD gene expression but that pertussis toxin-sensitive G proteins are not involved in the endotoxin induced elevation of lung MnSOD gene expression. We also show that treating rats with pertussis toxin decreased lung MnSOD activity approximately 50%. This decline in MnSOD activity occurred without a change in the lung activity of copper-zinc SOD, catalase, or glutathione peroxidase. In air-breathing rats, the pertussis toxin-induced decrease in MnSOD activity was associated with the development of lung edema, pleural effusion with a high concentration of protein, and biochemical evidence of lung oxygen toxicity. Compared to air-breathing rats, maintenance of pertussis toxin-treated rats under hypoxic or hyperoxic conditions respectively decreased or increased intrathoracic fluid. Endotoxin treatment elevated lung MnSOD activity and protected pertussis toxin-treated rats from an increase in intrathoracic fluid. PMID- 8200985 TI - Induction of vascular endothelial growth factor expression by prostaglandin E2 and E1 in osteoblasts. AB - PGE1 and PGE2 are potent stimulators of bone formation. Osteogenesis is strongly dependent on angiogenesis. Vascular endothelial growth factor (VEFG), a secreted endothelial cell-specific mitogen, has been implicated in physiological and pathological angiogenesis. The aim of this study was to examine the possible role of VEGF in PG stimulation of bone formation. We found that in rat calvaria derived osteoblast-enriched cells and in the osteoblastic RCT-3 cell line PGE2 and E1 increased VEGF mRNA and protein levels. The increased expression of VEGF mRNA produced by PGE2 was rapid (maximal at 1 h), transient (declined by 3 h), potentiated by cycloheximide, and abolished by actinomycin D. PGE2 had no effect on VEGF mRNA stability, suggesting transcriptional regulation of VEGF expression by PGF2. Rp-cAMP, a cAMP antagonist, suppressed VEGF mRNA induced by PGE2, indicating cAMP mediation. The upregulation of VEGF expression by PGE2 in the preosteoblastic RCT-1 cells was potentiated by treatment with retinoic acid, which induces the differentiation of these cells. The upregulation of VEGF mRNA by PGE2 was inhibited by dexamethasone treatment. In addition, Northern blot analysis showed that VEGF mRNA is expressed in adult rat tibia. In summary, we documented, for the first time, the expression of VEGF in osteoblasts and in bone tissue. Stimulation of VEGF expression by PGs and its suppression by glucocorticoids, which, respectively, stimulate and suppress bone formation, strongly implicate the involvement of VEGF in bone metabolism. PMID- 8200986 TI - Inhibition of human factor VIIIa by anti-A2 subunit antibodies. AB - Human inhibitory alloantibodies and autoantibodies to Factor VIII (FVIII) are usually directed toward the A2 and/or C2 domains of the FVIII molecule. Anti-C2 antibodies block the binding of FVIII to phospholipid, but the mechanism of action of anti-A2 antibodies is not known. We investigated the properties of a patient autoantibody, RC, and a monoclonal antibody, 413, that bind to the region which contains the epitopes of all anti-A2 alloantibodies or autoantibodies studied to date. mAb 413 and RC were noncompetitive inhibitors of a model intrinsic Factor X activation complex (intrinsic FXase) consisting of Factor IXa, activated FVIII (FVIIIa), and synthetic phospholipid vesicles, since they decreased the Vmax of intrinsic FXase by > 95% at saturating concentrations without altering the Km. This indicates that RC and mAb 413 either block the binding of FVIIIa to FIXa or phospholipid or interfere with the catalytic function of fully assembled intrinsic FXase, but they do not inhibit the binding of the substrate Factor X. mAb 413 did not inhibit the increase in fluorescence anisotropy that results from the binding of Factor VIIIa to fluorescein-5 maleimidyl-D-phenylalanyl-prolyl-arginyl-FIXa (Fl-M-FPR-FIXa) on phospholipid vesicles in the absence of Factor X, indicating it does not inhibit assembly of intrinsic FXase. Addition of Factor X to Fl-M-FPR-FIXa, FVIIIa, and phospholipid vesicles produced a further increase in fluorescence anisotropy and a decrease in fluorescence intensity. This effect was blocked completely by mAb 413. We conclude that anti-A2 antibodies inhibit FVIIIa function by blocking the conversion of intrinsic FXase/FX complex to the transition state, rather than by interfering with formation of the ground state Michaelis complex. PMID- 8200987 TI - Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency. AB - We report an inborn error of the tricarboxylic acid cycle, fumarase deficiency, in two siblings born to first cousin parents. They presented with progressive encephalopathy, dystonia, leucopenia, and neutropenia. Elevation of lactate in the cerebrospinal fluid and high fumarate excretion in the urine led us to investigate the activities of the respiratory chain and of the Krebs cycle, and to finally identify fumarase deficiency in these two children. The deficiency was profound and present in all tissues investigated, affecting the cytosolic and the mitochondrial fumarase isoenzymes to the same degree. Analysis of fumarase cDNA demonstrated that both patients were homozygous for a missense mutation, a G-955- >C transversion, predicting a Glu-319-->Gln substitution. This substitution occurred in a highly conserved region of the fumarase cDNA. Both parents exhibited half the expected fumarase activity in their lymphocytes and were found to be heterozygous for this substitution. The present study is to our knowledge the first molecular characterization of tricarboxylic acid deficiency, a rare inherited inborn error of metabolism in childhood. PMID- 8200988 TI - In vivo effects of IgA and IgG2a anti-CD3 isotype switch variants. AB - Side effects after the first administration of OKT3, a murine anti-CD3 monoclonal antibody (mAb) of the IgG2a class, are largely attributed to the release of cytokines as a result of T cell activation caused by interaction with Fc receptors (FcR) on human monocytes. As human monocytes possess FcR for murine IgG2a but not for IgA, it is expected that an anti-CD3 mAb of the IgA class causes less side-effects than an IgG2a anti-CD3 mAb of the same idiotype. To test this hypothesis we treated 20 renal transplant patients prophylactically with either IgG2a or IgA anti-CD3 mAb in a prospective randomized double-blind study. The patients received 0.5 mg anti-CD3 mAb, either IgA (T3.A) or IgG2a (T3.G2a), twice daily during 10 d. Rejection incidence after T3.A and T3.G2a was not significantly different. Side effects score after the first administration of mAb was significantly less after T3.A than after T3.G2a (0.7 vs 2.7, P = 0.002). IL-6 and gamma IFN levels increased significantly at 3 h after T3.G2a, but not after T3.A. The TNF peak level occurring at 1 h after T3.A was much lower than after T3.G2a. In plasma, complement and neutrophil activation products only increased after T3.G2a and not after T3.A. Both T3.A and T3.G2a resulted in a complete depletion of CD3+ cells, but after T3.A, CD3 depletion was of shorter duration than after IgG2a. Finally, in contrast to T3.G2a, T3.A did not affect coagulation and fibrinolysis. In conclusion, an anti-CD3 mAb of the IgA class causes hardly any cytokine release and less side-effects as compared with its IgG2a switch variant. Provided T3.A is sufficiently immunosuppressive, it is superior to OKT3. PMID- 8200989 TI - Comparative analysis of the apo(a) gene, apo(a) glycoprotein, and plasma concentrations of Lp(a) in three ethnic groups. Evidence for no common "null" allele at the apo(a) locus. AB - Distributions of plasma lipoprotein(a) (Lp[a]) concentrations exhibit marked interracial differences. Apolipoprotein(a) (apo[a]), the unique constituent of Lp(a), is highly polymorphic in length due to allelic variations in the number of kringle 4(K-4)-encoding sequences. Plasma Lp(a) concentrations are inversely related to the number of K-4 repeats in the apo(a) alleles. To determine the contribution of this length variation to the interracial variation in plasma Lp(a) levels, we compared apo(a) allele size, glycoprotein size, and plasma Lp(a) concentrations in Caucasians, Chinese, and African Americans. Caucasians and African Americans had very different distributions of plasma Lp(a) concentrations yet there was no significant difference in the overall frequency distributions of their apo(a) alleles. Over the entire size spectrum of apo(a) alleles, the plasma Lp(a) levels were higher in African Americans than in Caucasians. Conversely, Caucasians and Chinese had similar plasma Lp(a) concentrations but significantly different apo(a) allele size distributions. Therefore, interracial differences in the plasma concentrations of Lp(a) are not due to differences in the frequency distributions of apo(a) alleles. We also examined the relationship between apo(a) allele size and the presence of detectable plasma apo(a) protein in plasma. Apo(a) alleles associated with no detectable plasma protein were not of uniformly large size, as had been expected, but were distributed over the entire size spectrum. From this analysis, we conclude that there is no common "null" allele at the apo(a) locus. PMID- 8200990 TI - Cyclic AMP selectively enhances bradykinin receptor synthesis and expression in cultured arterial smooth muscle. Inhibition of angiotensin II and vasopressin response. AB - Bradykinin receptors on vascular smooth muscle may play an important role in regulating the endogenous effects of the vascular kallikrein-kinin system. The present study examined the effect of cyclic nucleotides on bradykinin-stimulated responses in cultured arterial smooth muscle cells. Short term stimulation (1 min) with cyclic AMP produced a variable inhibition of bradykinin-stimulated calcium mobilization which was lost in later passaged cells. However, long-term stimulation (24 h) produced a consistent increase in bradykinin-stimulated calcium mobilization in both early and late passaged cells. Further analysis demonstrated that chronic exposure to cAMP produced a twofold increase in both the number of cell surface bradykinin receptors and in bradykinin-stimulated phosphoinositide hydrolysis. The increase in bradykinin receptors was time dependent (> 7 h) and blocked by protein synthesis inhibitors, suggesting that cAMP enhanced the synthesis of new bradykinin receptors. The increase in bradykinin receptor binding and calcium mobilization was also stimulated by cholera toxin, forskolin, and isobutylmethylxanthine, but not isoproterenol or prostaglandin E2. Of considerable interest, prolonged exposure to cAMP inhibited both angiotensin II and arginine vasopressin-stimulated phosphoinositide hydrolysis and intracellular calcium mobilization. In summary, prolonged treatment with cAMP selectively stimulates the synthesis and expression of bradykinin receptors on arterial smooth muscle while decreasing the responsiveness to vasoconstrictor agonists such as angiotensin II and vasopressin. PMID- 8200991 TI - Defining the genetic origins of three rheumatoid synovium-derived IgG rheumatoid factors. AB - A major diagnostic marker in most rheumatoid arthritis (RA) patients is the rheumatoid factor (RF), an autoantibody that binds to the Fc region of IgG. To delineate the Ig genes and the underlying mechanism for RF production in RA patients, we applied a systematic approach to define the genetic origins of three IgG RFs derived from the synovial fluid of two RA patients. The results show that two of three IgG RF have substantial numbers of somatic mutations in their variable (V) regions, ranging from 13 to 23 mutations over a stretch of 291-313 nucleotides, resulting in a frequency of 4.4-7.8%. However, one IgG RF has only one mutation in each V region. This result indicates that an IgG RF may arise from a germline gene by very few mutations. The mutations occur mainly in the complementarity-determining regions (CDRs), and the mutations in the CDRs often lead to amino acid substitutions. Five of the six corresponding germline V genes have been found to encode either natural autoantibodies or autoantibodies in other autoimmune disorders; and three of the six V genes have been found in fetal liver. Taken together with other results, the data show that (a) several potentially pathogenic RFs in RA patients arise from natural autoantibodies, and (b) only a few mutations are required to convert the natural autoantibodies to IgG RFs. PMID- 8200992 TI - Protein kinase A and C site-specific phosphorylations of LAP (NF-IL6) modulate its binding affinity to DNA recognition elements. AB - LAP (NF-IL6 or C/EBP beta), is a liver transcriptional activator protein that confers liver-specific gene expression. Because LAP has a characteristic phosphoacceptor sequence for cAMP-dependent protein kinase A (PKA), we tested if in vitro phosphorylation of LAP by PKA modulates its interaction with specific DNA sequences. The major PKA phosphorylation site of LAP was identified as Ser105, which is a predicted PKA site. As expected, this PKA phosphorylation site disappears after mutation of Ser105 to Ala. Kinetic studies with LAP and LAP Asp105 (which mimics a phosphoserine residue) demonstrated that phosphorylation of Ser105 itself has no effect on DNA binding. Phosphorylation of other sites by PKA, identified in the region between Ser173 and Ser223 and at Ser240, by analysis of truncated and mutated LAP peptides, resulted in an inhibition of DNA binding. LAP was also phosphorylated by purified protein kinase C in vitro, and the major phosphoacceptor was shown to be Ser240 within the DNA-binding domain of LAP. Phosphorylation of LAP at this residue or introduction of a Ser240 to Asp mutation resulted in marked decrease in its binding to DNA. These results suggest that site-specific phosphorylations of LAP modulate transactivation of its target genes. PMID- 8200993 TI - Increased epinephrine and skeletal muscle responses to hypoglycemia in non insulin-dependent diabetes mellitus. AB - We evaluated skeletal muscle counterregulation during hypoglycemia in nine subjects with non-insulin-dependent diabetes mellitus (NIDDM) (HbA1c 9.4 +/- 0.5%, nl < 6.2%) compared with six normal controls, matched for age (51 +/- 3 and 49 +/- 5 yr, respectively) and body mass index (27.3 +/- 1.2 and 27.0 +/- 2.1 kg/m2). After 60 min of euglycemia (plasma insulin approximately 140 microU/ml), plasma glucose was lowered to 62 +/- 2 mg/dl by 120 min. Hypoglycemia induced a 2.2-fold greater increase in plasma epinephrine in NIDDM (P < 0.001), while the plasma glucagon response was blunted (P < 0.01). Hepatic glucose output ([3H 3]glucose) suppressed similarly during euglycemia, but during hypoglycemia was greater in NIDDM (P < 0.005). Conversely, glucose uptake during euglycemia was 150% greater in controls (P < 0.01) and remained persistently higher than in NIDDM during hypoglycemia. In NIDDM, plasma FFA concentrations were approximately fivefold greater (P < 0.001), and plasma lactate levels were approximately 40% higher than in controls during hypoglycemia (P < 0.01); the rates of glycolysis from plasma glucose were similar in the two groups despite a 49% lower rate of glucose uptake in NIDDM (3.4 +/- 0.9 vs. 6.9 +/- 1.3 mg/kg per minute, P < 0.001). Muscle glycogen synthase activity fell by 42% with hypoglycemia (P < 0.01) in NIDDM but not in controls. In addition, glycogen phosphorylase was activated by 56% during hypoglycemia in NIDDM only (P < 0.01). Muscle glucose-6 phosphate concentrations rose during hypoglycemia by a twofold greater increment in NIDDM (P < 0.01). Thus, skeletal muscle participates in hypoglycemia counterregulation in NIDDM, directly by decreased removal of plasma glucose and, indirectly, by providing lactate for hepatic gluconeogenesis. Consequently, in addition to inherent insulin resistance in NIDDM, the enhanced plasma epinephrine response during hypoglycemia may partially offset impaired glucagon secretion and counteract the effects of hyperinsulinemia on liver, fat, and skeletal muscle. PMID- 8200994 TI - Endothelin's biphasic effect on fluid absorption in the proximal straight tubule and its inhibitory cascade. AB - The effect of endothelin-1 (ET-1) on the proximal tubule remains unclear. This may be due to a biphasic effect on transport in this segment. We hypothesized that ET-1 has a biphasic effect on fluid absorption (Jv) in the proximal straight tubule and that its inhibitory effect is superimposed on its stimulatory effect. ET-1 (10(-13) M) stimulated Jv from 0.68 +/- 0.07 to 1.11 +/- 0.20 nl/mm/min, a 60% increase (P < 0.04). 10(-12) and 10(-10) M ET-1 had no significant effect. 10(-9) M ET-1 reduced Jv from 0.81 +/- 0.19 to 0.44 +/- 0.15 nl/mm/min (P < 0.009). Staurosporine (STP, 10(-8) M) prevented both 10(-9) and 10(-13) M ET-1 from altering Jv significantly indicating that protein kinase C (PKC) is involved. Indomethacin (10(-5) M) blocked the inhibition produced by 10(-9) M ET 1. ETI (10(-6) M), a lipoxygenase inhibitor, also blocked ET-1 inhibition of Jv. Interestingly ET-1 (10(-9) M) stimulated Jv in the presence of both indomethacin and ETI. When 10(-9) M ET-1 was added in the presence of 10(-5) M quinacrine, a phospholipase (PL) inhibitor, Jv also increased from 1.02 +/- 0.20 to 1.23 +/- 0.22 nl/mm/min (P < 0.03). STP blocked this increase. We conclude that (a) 10( 13) M ET-1 stimulates fluid absorption by activating PKC; (b) 10(-9) M ET-1 decreases Jv by PKC-, PL-, cyclooxygenase-, and lipoxygenase-dependent mechanisms; and (c) the inhibitory effect of ET-1 on Jv is superimposed on the stimulatory effect. PMID- 8200995 TI - Mineralocorticoids, hypertension, and cardiac fibrosis. AB - Uninephrectomized rats drinking 1% sodium chloride were given aldosterone (Aldo, 0.75 microgram/h, subcutaneous [s.c.] infusion), deoxycorticosterone (DOC, 20 mg/wk, s.c.), corticosterone (B, 2 mg/d, s.c.), or the antiglucocorticoid antiprogestin RU486 (2 mg/d, s.c.) for 8 wk, and hemodynamic and tissue responses were compared with a non-steroid-treated control group. Aldo and DOC markedly increased systolic BP and caused considerable (40-50%) cardiac hypertrophy; B and RU486 caused neither hypertension nor cardiac hypertrophy. Measurements of ventricular cross-sectional areas showed hypertrophy due to an increase in mass of the left ventricle only. Cardiac hydroxyproline concentration was increased considerably by Aldo and DOC, to a lesser degree by RU486, and not by B. Aldo markedly elevated left ventricular interstitial collagen (2.5-fold vs control, P < 0.01 vs all groups); other steroid treatments also increased interstitial collagen over control (DOC x 1.8-, RU486 x 1.6-, B x 1.3-fold), with identical responses for right and left ventricles (r = 0.94). A different pattern of perivascular fibrosis was noted; DOC elevated perivascular collagen (2.1-fold vs control, P < 0.01 vs all other groups); RU486 raised levels 1.4-fold vs control, but neither Aldo nor B significantly affected perivascular collagen. These data are consistent with interstitial cardiac fibrosis reflecting type I (mineralocorticoid) receptor occupancy by administered Aldo or DOC, or by elevated endogenous B after type II (glucocorticoid) receptor blockade after RU486 administration; perivascular fibrosis may reflect a composite response after type I receptor agonist/type II glucocorticoid receptor antagonist occupancy. PMID- 8200996 TI - Insulin regulation of renal glucose metabolism in conscious dogs. AB - Previous studies indicating that postabsorptive renal glucose production is negligible used the net balance technique, which cannot partition simultaneous renal glucose production and glucose uptake. 10 d after surgical placement of sampling catheters in the left renal vein and femoral artery and a nonobstructive infusion catheter in the left renal artery of dogs, systemic and renal glucose and glycerol kinetics were measured with peripheral infusions of [3-3H]glucose and [2-14C]glycerol. After baseline measurements, animals received a 2-h intrarenal infusion of either insulin (n = 6) or saline (n = 6). Left renal vein insulin concentration increased from 41 +/- 8 to 92 +/- 23 pmol/l (P < 0.05) in the insulin group, but there was no change in either arterial insulin, (approximately 50 pmol/l), glucose concentrations (approximately 5.4 mmol/l), or glucose appearance (approximately 18 mumol.kg-1.min-1). Left renal glucose uptake increased from 3.1 +/- 0.4 to 5.4 +/- 1.4 mumol.kg-1.min-1 (P < 0.01) while left renal glucose production decreased from 2.6 +/- 0.9 to 0.7 +/- 0.5 mumol.kg-1.min 1 (P < 0.01) during insulin infusion. Renal gluconeogenesis from glycerol decreased from 0.23 +/- 0.06 to 0.17 +/- 0.04 mumol.kg-1.min-1 (P < 0.05) during insulin infusion. These results indicate that renal glucose production and utilization account for approximately 30% of glucose turnover in postabsorptive dogs. Physiological hyperinsulinemia suppresses renal glucose production and stimulates renal glucose uptake by approximately 75%. We conclude that the kidney makes a major contribution to systemic glucose metabolism in the postabsorptive state. PMID- 8200997 TI - Multiple lipolysis defects in the insulin resistance (metabolic) syndrome. AB - Bearing in mind the importance of upper-body obesity for the insulin resistance (or metabolic) syndrome and the abnormalities in free fatty acid metabolism associated with this disorder, the regulation of lipolysis in isolated subcutaneous adipocytes was investigated in 13 72-yr old upper-body obese men with insulin resistance and glucose intolerance and in 10 healthy 72-yr-old men. There was a marked resistance to the lipolytic effect of noradrenaline in the metabolic syndrome due to defects at two different levels in the lipolytic cascade. First, an 80-fold decrease in sensitivity to the beta 2-selective agonist terbutaline (P < 0.001) which could be ascribed to a 50% reduced number of beta 2-receptors (P < 0.005) as determined with radioligand binding. The groups did not differ as regards dobutamine (beta 1) or clonidine (alpha-2) sensitivity, nor beta 1-receptor number. The mRNA levels for beta 1- and beta 2 receptors were similar in the two groups. Second, the maximum stimulated lipolytic rate was markedly reduced in the metabolic syndrome. This was true for isoprenaline (nonselective beta-agonist), forskolin (activating adenylyl cyclase), and dibutyryl cAMP (activating protein kinase). In regression analysis, the observed abnormalities in lipolysis regulation correlated in an independent way with the degree of glucose intolerance (r = -0.67) and beta 2-receptor number with insulin resistance (r = 0.67). In conclusion, the results of this study indicate the existence of lipolytic resistance to catecholamines in the adipose tissue of elderly men with the metabolic syndrome, which may be of importance for impaired insulin action and glucose intolerance. The resistance is located at a posttranscriptional level of beta 2-receptor expression and at the protein kinase hormone sensitive lipase level. PMID- 8200998 TI - Prenatal immune challenge alters the hypothalamic-pituitary-adrenocortical axis in adult rats. AB - We investigated whether non-abortive maternal infections would compromise fetal brain development and alter hypothalamic-pituitary-adrenocortical (HPA) axis functioning when adult. To study putative teratogenic effects of a T cell mediated immune response versus an endotoxic challenge, 10-d-pregnant rats received a single intraperitoneal injection of 5 x 10(8) human red blood cells (HRBC) or gram-negative bacterial endotoxin (Escherichia coli LPS: 30 micrograms/kg). The adult male progeny (3 mo old) of both experimental groups showed increased basal plasma corticosterone levels. In addition, after novelty stress the HRBC group, but not the LPS group, showed increased ACTH and corticosterone levels. Both groups showed substantial decreases in mineralocorticoid (MR) and glucocorticoid receptor (GR) levels in the hippocampus, a limbic brain structure critical for HPA axis regulation, whereas GR concentrations in the hypothalamus were unchanged and in anterior pituitary were slightly increased. HRBC and LPS indeed stimulated the maternal immune system as revealed by specific anti-HRBC antibody production and enhanced IL-1 beta mRNA expression in splenocytes, respectively. This study demonstrates that a T cell-mediated immune response as well as an endotoxic challenge during pregnancy can induce anomalies in HPA axis function in adulthood. Clinically, it may be postulated that disturbed fetal brain development due to prenatal immune challenge increases the vulnerability to develop mental illness involving inadequate responses to stress. PMID- 8200999 TI - Exposure of the hydrophobic components of porcine lung surfactant to oxidant stress alters surface tension properties. AB - We have tested the hypothesis that oxidation of lung surfactant results in loss of surface tension lowering function. Porcine lung surfactant was exposed to conditions known to cause lipid peroxidation (0.2 mM FeCl2 + 0.1 mM H2O2 or 5 microM CuCl2). Lipid peroxidation was verified by detection of conjugated dienes, thiobarbituric acid reactive substances, fluorescent products, hydroxy alkenals, and loss of unsaturated fatty acids. Exposed samples had significantly diminished surface tension lowering ability in vitro as measured in a bubble surfactometer. Samples exposed to FeCl2 + H2O2 had significantly diminished surface tension lowering ability in vivo as indicated by their reduced ability to improve lung compliance of surfactant-deficient fetal rabbits. Oxidation of phospholipid mixtures with surface tension lowering activity and containing unsaturated acyl groups resulted in partial loss of activity as determined in vitro. These results suggest that the effect of oxidants on lung surfactant function is due, in part, to effects on the phospholipid components and that acute pulmonary inflammation accompanied by oxygen radical production may result in surfactant lipid peroxidation and loss of surface tension lowering function. PMID- 8201000 TI - Potentiation by granulocyte macrophage colony-stimulating factor of lipopolysaccharide toxicity in mice. AB - GM-CSF is known to prime leukocytes for inflammatory stimuli in vitro. The objective of this study was to investigate the role of GM-CSF in vivo in a systemic inflammatory reaction syndrome. The results demonstrate a potentiation of LPS toxicity by GM-CSF in a mortality model as well as in a septic liver failure model in mice. Pretreatment of animals with 50 micrograms/kg GM-CSF induced lethality within 24 h in mice challenged with a subtoxic dose of LPS while controls survived > 72 h. A monoclonal anti-GM-CSF antibody significantly protected against a lethal LPS dose. Serum GM-CSF was inducible by LPS and peaked at 2 h. GM-CSF pretreatment dramatically potentiated systemic TNF release and hepatotoxicity induced by a subtoxic dose of LPS in galactosamine-sensitized mice. Potentiation of LPS hepatotoxicity was possible until 30 min after LPS challenge. Polyclonal anti-GM-CSF IgG protected against septic liver failure in this model and attenuated serum TNF concentrations. In vitro an ex vivo experiments revealed that after GM-CSF pretreatment LPS-induced IL-1 release from bone marrow or spleen cells was also enhanced. These findings suggest that GM-CSF represents an endogenous enhancer of LPS-induced organ injury, possibly by potentiating the release of proinflammatory cytokines such as TNF and IL-1. PMID- 8201001 TI - Glucose-induced changes in Na+/H+ antiport activity and gene expression in cultured vascular smooth muscle cells. Role of protein kinase C. AB - Increased Na+/H+ antiport activity has been implicated in the pathogenesis of hypertension and vascular disease in diabetes mellitus. The independent effect of elevated extracellular glucose concentrations on Na+/H+ antiport activity in cultured rat vascular smooth muscle cells (VSMC) was thus examined. Amiloride sensitive 22Na+ uptake by VSMC significantly increased twofold after 3 and 24 h of exposure to high glucose medium (20 mM) vs. control medium (5 mM). Direct glucose-induced Na+/H+ antiport activation was confirmed by measuring Na(+) dependent intracellular pH recovery from intracellular acidosis. High glucose significantly increased protein kinase C (PKC) activity in VSMC and inhibition of PKC activation with H-7, staurosporine, or prior PKC downregulation prevented glucose-induced increases in Na+/H+ antiport activity in VSMC. Northern analysis of VSMC poly A+ RNA revealed that high glucose induced a threefold increase in Na+/H+ antiport (NHE-1) mRNA at 24 h. Inhibiting this increase in NHE-1 mRNA with actinomycin D prevented the sustained glucose-induced increase in Na+/H+ antiport activity. In conclusion, elevated glucose concentrations significantly influence vascular Na+/H+ antiport activity via glucose-induced PKC dependent mechanisms, thereby providing a biochemical basis for increased Na+/H+ antiport activity in the vascular tissues of patients with hypertension and diabetes mellitus. PMID- 8201002 TI - Systemic administration of ciliary neurotrophic factor induces cachexia in rodents. AB - Ciliary neurotrophic factor (CNTF) has previously been shown to promote the survival of several classes of neurons and glial. We report here that in addition to its effects on the nervous system, CNTF can induce potent effects in extra neural tissues. Implantation of C6 glioma cells engineered to secrete CNTF either subcutaneously or into the peritoneal cavity of adult mice, or systemic injections of purified rat or human recombinant CNTF, resulted in a rapid syndrome of weight loss resulting in death over a period of 7-10 d. This weight loss could not be explained by a reduction in food intake and involved losses of both fat and skeletal muscle. CNTF also induced the synthesis of acute phase proteins such as haptoglobin. Implantation of C6 lines expressing a nonsecreted form of CNTF, or the parental C6 line itself, did not result in wasting effects. Analysis of this CNTF-induced wasting indicates similarities with the previously described cachectins, tumor necrosis factor, interleukin 6, and leukemia inhibitory factor, but does not involve the induction of these cytokines. PMID- 8201003 TI - Inhibition of amiloride-sensitive apical Na+ conductance by acetylcholine in rabbit cortical collecting duct perfused in vitro. AB - We examined effects of acetylcholine (ACh) on the electrical parameters and intracellular Ca2+ concentration ([Ca2+]i) in the isolated rabbit cortical collecting duct (CCD) perfused in vitro using the conventional microelectrode technique and microscopic fluorescence spectrophotometry. ACh (10(-8) to 10(-5) M) in the bath caused a positive deflection of the transepithelial voltage (VT) and an increase in [Ca2+]i. Carbachol also showed similar but smaller effects. The effects of ACh were antagonized by muscarinic receptor antagonists. ACh at 10(-6) M hyperpolarized the apical membrane voltage and increased the fractional resistance of the apical membrane of the collecting duct cells accompanied by a positive deflection of VT and an increase in transepithelial resistance, whereas it did not affect these parameters in the beta-intercalated cells. In the presence of 10(-5) M amiloride in the lumen, the effects of ACh were almost completely abolished. The ACh-induced increase in [Ca2+]i is accounted for by the release of Ca2+ from intracellular store and Ca2+ entry from the bath. In the absence of Ca2+ in the bath, the ACh-induced changes in electrophysiological parameters were significantly smaller than those observed in the presence of Ca2+. Both phorbol-12-myristate-13-acetate (PMA) and phorbol-12,13-dibutylate (PDBu), activators of protein kinase C (PKC), also inhibited the apical Na+ conductance. In the presence of PMA or PDBu in the bath, ACh did not show further inhibitory effect. 1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine, an inhibitor of PKC, partially attenuated the effect of ACh. These observations indicate that ACh inhibits the apical Na+ conductance partly by both increasing [Ca2+]i and activating PKC. Such an action of ACh may partially explain its natriuretic effect. PMID- 8201004 TI - Role of controlled cardiac reoxygenation in reducing nitric oxide production and cardiac oxidant damage in cyanotic infantile hearts. AB - Cardiopulmonary bypass (CPB) is used increasingly to correct cyanotic heart defects during early infancy, but myocardial dysfunction is often seen after surgical repair. This study evaluates whether starting CPB at a conventional, hyperoxic pO2 causes an "unintentional" reoxygenation (ReO2) injury. We subjected 2-wk-old piglets to ventilator hypoxemia (FIO2 approximately 0.06, pO2 approximately 25 mmHg) followed by 5 min of ReO2 on CPB before instituting cardioplegia. CPB was begun in hypoxemic piglets by either abrupt ReO2 at a pO2 of 400 mmHg (standard clinical practice) or by maintaining pO2 approximately 25 mmHg on CPB until controlling ReO2 with blood cardioplegic arrest. The effects of abrupt vs. gradual ReO2 without surgical ischemia (blood cardioplegia) were also compared. Myocardial nitric oxide (NO) production (chemiluminescence measurements of NO2- + NO3-) and conjugated diene (CD) generation (spectrophotometric A233 measurements of lipid extracts) using aortic and coronary sinus blood samples were assessed during cardioplegic induction. 30 min after CPB, left ventricular end-systolic elastance (Ees, catheter conductance method) was used to determine cardiac function. CPB and blood cardioplegic arrest caused no functional or biochemical change in normoxic (control) hearts. Abrupt ReO2 caused a depression of myocardial function (Ees = 25 +/- 5% of control). Functional depression was relatively unaffected by gradual ReO2 without blood cardioplegia (34% recovery of Ees), and abrupt ReO2 immediately before blood cardioplegia caused a 10-fold rise in cardiac NO and CD production, with subsequent depression of myocardial function (Ees 21 +/- 2% of control). In contrast, controlled cardiac ReO2 reduced NO production 94%, CD did not rise, and Ees was 83 +/- 8% of normal. We conclude ReO2 injury is related to increased NO production during abrupt ReO2, nullifies the cardioprotective effects of blood cardioplegia, and that controlled cardiac ReO2 when starting CPB to correct cyanotic heart defects may reduce NO production and improve myocardial status postoperatively. PMID- 8201005 TI - Chronic nitric oxide inhibition in utero produces persistent pulmonary hypertension in newborn lambs. AB - Persistent pulmonary hypertension of the newborn (PPHN) is associated with chronic intrauterine events. Acute nitric oxide (NO) inhibition attenuates the normal increase in pulmonary blood flow at birth. We investigated whether chronic NO inhibition in utero causes persistent pulmonary hypertension. 11 fetal lambs received either a continuous infusion of N omega-nitro-L-arginine (an NO synthesis inhibitor) or 0.9% saline. Before infusion, acetylcholine (dependent upon endogenous NO production) and sodium nitroprusside (which releases its own NO) produced potent pulmonary vasodilation. After 10.5 +/- 1.5 d of infusion, acetylcholine did not produce pulmonary vasodilation in N omega-nitric-L-arginine treated fetal lambs, but did in saline-treated fetal lambs; sodium nitroprusside produced pulmonary vasodilation in both groups. Immediately after birth, at 140 d of gestation, during the 3-h study period, mean pulmonary arterial pressure did not decrease in N omega-nitro-L-arginine-treated lambs; the increase in pulmonary blood flow and decrease in pulmonary vascular resistance were markedly attenuated compared to saline-treated lambs. These hemodynamic derangements were reversed by L-arginine. There were no anatomic abnormalities in the pulmonary circulation. Chronic NO inhibition in utero reproduces many of the physiologic derangements of PPHN. Intrauterine events which result in endothelial dysfunction and inhibition of NO may produce the physiologic derrangements of PPHN. PMID- 8201006 TI - Altered adenylyl cyclase activities and G-protein abnormalities in portal hypertensive rabbits. AB - Portal hypertension (PHT) is characterized by splanchnic hyperemia due to a reduction in mesenteric vascular resistance. We hypothesized that alterations in the activity of a guanine-nucleotide regulatory protein (G-protein) might be partially responsible for the marked circulatory disturbances observed in PHT. We, therefore, determined alterations in adenylyl cyclase/cAMP system in prehepatic portal hypertensive rabbits and correlated these changes to the activity of a G-protein. Basal and G-protein-stimulated adenylyl cyclase activities were lower in the PHT superior mesenteric artery (22-26%) and thoracic aorta (31-46%) membranes, but higher (178-321%) in portal vein. The functional activity of Gi alpha proteins (pertussis toxin-catalyzed ADP-dependent ribosylation) increased in the PHT superior mesenteric artery and thoracic aorta, but decreased in portal vein. Immunodetection revealed an increase in the Gi alpha protein subunits (Gi alpha 1/Gi alpha 2 and Gi alpha 3/Go alpha) in PHT thoracic aorta, without any change in Gs alpha proteins; and a decrease in the amount of Gi alpha proteins in PHT portal vein. There was no change in the amount of Gs alpha/Gi alpha in the PHT superior mesenteric artery. We conclude the hemodynamic alterations of PHT are associated with intrinsic alterations in G protein-enzyme effector systems. These alterations are vessels specific and suggest a possible unique global derangement underlying the vasculopathy of PHT. PMID- 8201007 TI - Genetic mapping of two new blood pressure quantitative trait loci in the rat by genotyping endothelin system genes. AB - The endothelin system, consisting of a series of potent vasoconstrictor peptides and their receptors, is potentially important in the control of blood pressure. We found that the gene coding for endothelin-2 (ET2), also known as vasoctive intestine peptide, cosegregated strongly with systolic blood pressure in a F2 population [F2(S x LEW)] derived from a cross of the Dahl salt-sensitive (S) rat and the Lewis (LEW/NCrlBR) (LEW) rat. The ET2 locus was assigned to rat chromosome 5. The testis-specific histone (HITH) locus also strongly cosegregated with blood pressure in the F2(S x LEW) population and was assigned to rat chromosome 17. Genetic maps of the regions containing the quantitative trait loci (QTL) for blood pressure on chromosomes 5 and 17 were constructed and the QTL were localized using the MAPMAKER/QTL program. The rat genes for endothelin-1, endothelin-3, and endothelin receptor A did not cosegregate with blood pressure in several F2 populations tested and were assigned to rat chromosomes 17, 3, and 19, respectively. Endothelin receptor B cosegregated weakly with blood pressure and was provisionally assigned to rat chromosome 15. We conclude that, in the rat, one new blood pressure QTL is located on chromosome 5 marked by the ET2 locus and another new QTL is located on chromosome 17 near the HITH locus. PMID- 8201008 TI - Low density lipoprotein enhances the cellular action of arginine vasopressin in rat glomerular mesangial cells in culture. AB - The present study was undertaken to determine whether low density lipoprotein (LDL) modulates the cellular action of arginine vasopressin (AVP) in rat glomerular mesangial cells in culture. AVP increased cellular free calcium ([Ca2+]i) in a dose-dependent manner. When cells were preincubated for 24 h with 10 microgram/ml LDL, the 1 x 10(-7) M AVP-mobilized [Ca2+]i was 874 nM, a value significantly greater than that of 375 nM in the intact cells. AVP caused a biphasic change in cellular pH (pHi), namely, an early acidification followed by a sustained alkalinization, and the change in pHi produced by AVP was also enhanced by LDL. AVP stimulated a 2.2-fold increase in [3H]thymidine incorporation, an effect significantly greater in the presence of 10 micrograms/ml LDL. Furthermore, 1 x 10(-7) M AVP significantly activated mitogen activated protein kinase from 14.0 to 24.5 pmol/mg protein. Such an activation was significantly enhanced by the LDL pretreatment. Both [3H]thymide incorporation and mitogen-activated protein kinase were not altered by 10 micrograms/ml LDL. [3H]AVP receptor binding was not affected by the LDL pretreatment. 1 x 10(-7) M AVP increased inositol trisphosphate production by 1.9 fold, an effect significantly greater in the presence of LDL. These results indicate that LDL enhances the cellular action of AVP and the AVP-stimulated cellular proliferation in glomerular mesangial cells. A site of action of LDL is the hydrolysis of phosphatidylinositol. PMID- 8201009 TI - Effects of glucose on sorbitol pathway activation, cellular redox, and metabolism of myo-inositol, phosphoinositide, and diacylglycerol in cultured human retinal pigment epithelial cells. AB - Sorbitol (aldose reductase) pathway flux in diabetes perturbs intracellular metabolism by two putative mechanisms: reciprocal osmoregulatory depletion of other organic osmolytes e.g., myo-inositol, and alterations in NADPH/NADP+ and/or NADH/NAD+. The "osmolyte" and "redox" hypotheses predict secondary elevations in CDP-diglyceride, the rate-limiting precursor for phosphatidylinositol synthesis, but through different mechanisms: the "osmolyte" hypothesis via depletion of intracellular myo-inositol (the cosubstrate for phosphatidylinositol-synthase) and the "redox" hypothesis through enhanced de novo synthesis from triose phosphates. The osmolyte hypothesis predicts diminished phosphoinositide-derived arachidonyl-diacylglycerol, while the redox hypothesis predicts increased total diacylglycerol and phosphatidic acid. In high aldose reductase expressing retinal pigment epithelial cells, glucose-induced, aldose reductase inhibitor-sensitive CDP-diglyceride accumulation and inhibition of 32P-incorporation into phosphatidylinositol paralleled myo-inositol depletion (but not cytoplasmic redox, that was unaffected by glucose) and depletion of arachidonyl diacylglycerol. 3 mM pyruvate added to the culture medium left cellular redox unaltered, but stimulated Na(+)-dependent myo-inositol uptake, accumulation, and incorporation into phosphatidylinositol. These results favor myo-inositol depletion rather than altered redox as the primary cause of glucose-induced aldose reductase-related defects in phospholipid metabolism in cultured retinal pigment epithelial cells. PMID- 8201011 TI - The antioxidant butylated hydroxytoluene prevents early cholesterol-induced microcirculatory changes in rabbits. AB - Microcirculation was studied during 10 wk in untreated rabbits (n = 13) and in rabbits treated with dietary addition of 1% cholesterol (n = 13), 1% cholesterol + 1% of the antioxidant BHT (butylated hydroxytoluene) (n = 11), or 1% BHT (n = 5). The studies were performed by direct intravital microscopic imaging of the left and right conjunctivae with the use of a stereo microscope and a high resolution television camera. Microvessel diameter, erythrocyte flow velocity, and microhemorheologic conditions were evaluated quantitatively via a computer assisted digital image processing system. Significant and marked changes occurred in all the above variables as a consequence of cholesterol feeding. After 3 wk of feeding there was a dramatic decrease (approximately 30%) in blood flow velocity in arterioli of the third order (P < 0.0001), accompanied by aggregation of cells in 40-50% of the smaller conjunctival vessels (P < 0.0001). These changes were enhanced further during the following 7 wk of treatment. All the above changes in the microcirculation were markedly reduced by the addition of BHT treatment. The diameter of the above arterioli decreased in the purely cholesterol-fed group (P < 0.005), whereas this did not occur in the group fed both cholesterol and BHT. In rabbits fed BHT in the absence of cholesterol, there was no significant effect on any assessed microcirculatory variable. In conclusion, the results demonstrate that the antioxidant BHT prevented early cholesterol-induced microcirculatory changes. This prevention occurred in the absence of a reduction of blood lipid levels. The results provide strong support for the hypothesis that a considerable part of the effects on microcirculation in hypercholesterolemia may be due to cholesterol-induced oxidations and not to cholesterol itself. The results are discussed in relation to the previously demonstrated antiatherogenic effect of BHT and the possible use of antioxidants in the therapy and prophylaxis of atherosclerosis. PMID- 8201010 TI - Na,K-ATPase in diabetic rat small intestine. Changes at protein and mRNA levels and role of glucagon. AB - Na,K-ATPase activity and isoform expression were measured in rat small intestinal mucosa taken from both normal and streptozocin-treated diabetic rats. Enzyme activity and abundance was 1.7-2.3-fold higher in rats diabetic for 2 wk than in controls. This was associated with 1.4-1.7-fold increases in small intestinal protein and DNA content. Ouabain inhibition curves of Na,K-ATPase were monophasic with Kis of 2.6 +/- 1.4 x 10(-4) and 2.0 +/- 1.2 x 10(-4) M for control and diabetic rats, respectively (NS). Northern blot analysis revealed a 2.5-fold increase in mRNA alpha 1 and a 3.4-fold increase in mRNA beta 1 in diabetic rats relative to controls. Two thirds of this increase occurred within 24h after injection of streptozocin. Immunoblots of intestinal enzyme preparations from diabetic and control rats indicated the presence of alpha 1 and beta 1 subunits but not of alpha 2 or alpha 3. Administration of glucagon (80 micrograms/kg) to normal rats daily for 14-16 d increased mRNA alpha 1 3.1-fold but did not increase mRNA beta 1 or enzyme activity. In experimental diabetes, alpha 1 and beta 1 isoforms of Na,K-ATPase are coordinately upregulated at both protein and mRNA levels, an effect which appears to be partially mediated by the associated hyperglucagonemia. PMID- 8201012 TI - Retrobulbar T cells from patients with Graves' ophthalmopathy are CD8+ and specifically recognize autologous fibroblasts. AB - Graves' ophthalmopathy is an autoimmune condition characterized by T cell infiltration of the retrobulbar tissue. Phenotypic and functional analysis of these infiltrating cells may provide insight into the pathogenesis of the disease. IL-2-responsive cells were therefore grown out of the retrobulbar tissue from two patients with severe Graves' ophthalmopathy undergoing orbital decompression surgery, and six T cell lines were established and characterized. They consisted predominantly of CD8 + CD45RO+ cells and secreted IL-4, IFN-gamma, and IL-10 upon activation. When screened for their antigen reactivity, all lines proliferated in response to stimulation with autologous retrobulbar fibroblasts in an HLA class I-restricted manner, but did not recognize autologous peripheral blood mononuclear cells, crude eye muscle extract, allogeneic cells, or purified protein derivate of Mycobacterium tuberculosis. In contrast, PBMC from the same patients responded readily to purified protein derivate of Mycobacterium tuberculosis and allogeneic PBMC, but did not recognize autologous fibroblasts. Interestingly, only one of the six retrobulbar T cell lines displayed cytotoxicity towards its specific target cell population. These results suggest that the retrobulbar fibroblasts are a major T cell target in Graves' ophthalmopathy. Pronounced cytokine production in the absence of target cell cytotoxicity may explain fibroblast proliferation, glycosaminoglycan secretion, and secondary eye muscle enlargement in this condition. PMID- 8201014 TI - The inverse association of plasma lipoprotein(a) concentrations with apolipoprotein(a) isoform size is not due to differences in Lp(a) catabolism but to differences in production rate. AB - Lipoprotein(a) (Lp[a]) is an atherogenic lipoprotein which is similar in structure to low density lipoproteins (LDL) but contains an additional protein called apolipoprotein(a) (apo[a]). Apo(a) is highly polymorphic in size, and there is a strong inverse association between the size of the apo(a) isoform and the plasma concentration of Lp(a). We directly compared the in vivo catabolism of Lp(a) particles containing different size apo(a) isoforms to establish whether there is an effect of apo(a) isoform size on the catabolic rate of Lp(a). In the first series of studies, four normal subjects were injected with radio-labeled S1 Lp(a) and S2-Lp(a) and another four subjects were injected with radiolabeled S2 Lp(a) and S4-Lp(a). No significant differences in fractional catabolic rate were found between Lp(a) particles containing different apo(a) isoforms. To confirm that apo(a) isoform size does not influence the rate of Lp(a) catabolism, three subjects heterozygous for apo(a) were selected for preparative isolation of both Lp(a) particles. The first was a B/S3-apo(a) subject, the second a S4/S6-apo(a) subject, and the third an F/S3-apo(a) subject. From each subject, both Lp(a) particles were preparatively isolated, radiolabeled, and injected into donor subjects and normal volunteers. In all cases, the catabolic rates of the two forms of Lp(a) were not significantly different. In contrast, the allele-specific apo(a) production rates were more than twice as great for the smaller apo(a) isoforms than for the larger apo(a) isoforms. In a total of 17 studies directly comparing Lp(a) particles of different apo(a) isoform size, the mean fractional catabolic rate of the Lp(a) with smaller size apo(a) was 0.329 +/- 0.090 day-1 and of the Lp(a) with the larger size apo(a) 0.306 +/- 0.079 day-1, not significantly different. In summary, the inverse association of plasma Lp(a) concentrations with apo(a) isoform size is not due to differences in the catabolic rates of Lp(a) but rather to differences in Lp(a) production rates. PMID- 8201013 TI - Abnormal Na+/H+ antiporter phenotype and turnover of immortalized lymphoblasts from type 1 diabetic patients with nephropathy. AB - Cellular Na+/H+ exchanger (NHE) activity is elevated in type 1 diabetic patients with nephropathy and patients with essential hypertension. The characteristics of this NHE phenotype in hypertension (raised Vmax and a lowered Hill coefficient) are preserved in Epstein-Barr virus-transformed lymphoblasts from hypertensive patients. In this study, we have determined NHE kinetics in cultured lymphoblasts from diabetic patients with and without nephropathy, with nondiabetic controls, using fluorometry with the pH indicator 2,7'-bis-(carboxyethyl)-5,6 carboxyfluorescein and estimation of NHE isoform 1 (NHE-1) density with specific polyclonal antibodies. The Vmax of NHE was elevated significantly, and the Hill coefficient for internal H+ binding was lowered in cells from patients with diabetic nephropathy compared with both normal controls and normoalbuminuric diabetic patients. NHE-1 density as measured by Western blotting was similar in all groups. The turnover number of NHE-1 was thus elevated in cells from nephropathy patients. This phenotype in cells from diabetic nephropathy patients resembles that in essential hypertension and suggests that such patients may have a predisposition to hypertension. Moreover, as these changes persist in cultured lymphoblasts in vitro, these cells should provide a cell culture model to further define the basic mechanisms leading to NHE activation in diabetic nephropathy. PMID- 8201016 TI - Differential response of neutral endopeptidase 24.11 ("enkephalinase"), and cholinergic and opioidergic markers to hypoglossal axotomy. AB - Neutral endopeptidase 24.11 (NEP; "enkephalinase") may inactivate a number of centrally active neuropeptides including the enkephalins and substance P. In most areas of the central nervous system, the cell types which express NEP activity are not known. The hypoglossal nucleus (N.XII) was selected as a model system to characterize the cytochemical localization of NEP. The effect of hypoglossal nerve axotomy upon the distribution of NEP activity in the hypoglossal nucleus was compared to the effect upon cholinergic markers, the mu opiate receptor, and the enkephalins. By use of a fluorescence histochemical method, NEP was localized at all levels of N.XII to the soma and proximal processes of the majority of the apparent motor neurons in the nucleus. Fluorescent double-labeling studies revealed the presence of numerous enkephalinergic varicosities which localized to the neuropil surrounding NEP-stained motor neurons. To determine whether NEP was synthesized by these motor neurons, 18 rats received a unilateral transection of the hypoglossal nerve. A pronounced decrease in NEP staining in N.XII was observed on the operated side as early as 3 days following axotomy. This decrease persisted at all levels of the nucleus for about 5 weeks. By 7 weeks, the staining between the control and operated sides was indistinguishable. By contrast, there was no apparent change in the density or distribution of enkephalin-immunoreactive varicosities in five animals examined 6 to 32 days following axotomy. Radioligand binding of [3H]DAMGO to the mu-opiate receptor in N.XII was studied in 20 animals by quantitative autoradiography at 2, 6, and 11 days after axotomy. No significant changes in the level of radioligand binding to the mu-receptor were detected in response to axotomy. In contrast to the opiate system, the cholinergic enzymes choline acetyltransferase, acetylcholinesterase, and pseudocholinesterase showed a coordinate decrease in motor neuron-associated staining on the operated side of N.XII at 3, 6, and 11 days following axotomy which paralleled the decrease in NEP staining. By contrast, the lysosomal enzyme marker, acid phosphatase, showed a pronounced increase in staining on the operated side. The results of this study are consistent with the synthesis of NEP by cholinergic N.XII motor neurons and indicates that the enkephalins and NEP in N.XII are closely associated, but derive from separate neuronal populations. The widespread overlap in the distribution of NEP-stained motor neurons and enkephalinergic varicosities in N.XII provides additional anatomical support for a potential role for NEP in the inactivation of centrally active enkephalins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201015 TI - Incorporation of chylomicron fatty acids into the developing rat brain. AB - The developing brain obtains polyunsaturated fatty acids from the circulation, but the mechanism and route of delivery of these fatty acids are undetermined. 14C-labeled chylomicrons were prepared by duodenal infusion of [1-14C]16:0, [1 14C]18:2(n-6), [1-14C]18:3(n-3), or [1-14C]22:6(n-3) into adult donor rats, and were individually injected into hepatectomized 2-wk-old suckling rats. After minor correction for trapped blood in the brain, the incorporation of chylomicron fatty acids after 30 min was nearly half that of a co-injected free fatty acid reference. [1-14C]22:6(n-3)-labeled chylomicrons showed an average 65% greater incorporation than chylomicrons prepared from the other fatty acids. This apparent selectivity may have been partly due to lower oxidation of 22:6(n-3) in the brain compared to the other fatty acids tested, based on recovered water soluble oxidation products. The bulk of the radioactivity in the brain was found in phospholipid and triacylglycerol, except that animals injected with [1 14C]22:6(n-3) chylomicrons showed considerable incorporation also into the fatty acid fraction instead of triacylglycerol. These data show that chylomicrons may be an important source of fatty acids for the developing rat brain. PMID- 8201017 TI - The ontogeny of GAP-43 (neuromodulin) mRNA in postnatal rat brain: evidence for a sex dimorphism. AB - GAP-43 is a membrane-bound protein selectively concentrated in axonal growth cones during brain development and implicated in axonal outgrowth and elongation. A sex dimorphism in the number of synapses in certain regions of the adult rat brain has been attributed to differences in gonadal steroid hormone action during early postnatal life. The results of recent studies have demonstrated that gonadal steroids modulate GAP-43 mRNA in regions of the postnatal and adult brain where steroid hormone receptors are concentrated. Since gonadal steroids influence the development of the sexually undifferentiated brain during the first few weeks of postnatal life, the present study investigated the ontogeny of GAP 43 mRNA in the male and female rat brain between postnatal days 1 and 25. On postnatal days 1, 3, 6, 12, 18, and 25, brains were collected from male and female postnates and frozen, and 16 microns cryostat sections were processed and hybridized with a 35S-labeled antisense riboprobe complementary to GAP-43 mRNA. Evaluation of film autoradiograms demonstrated a widespread distribution of GAP 43 mRNA in postnatal brain regions, including the cerebral cortex; bed nucleus of the stria terminalis; and medial preoptic area, ventromedial nucleus, and arcuate nucleus of the hypothalamus. Densitometric measurements revealed that GAP-43 mRNA was transiently elevated during early postnatal life, with a subsequent decrease during brain maturation, although the pattern of change varied among the brain regions investigated. In addition, the level of GAP-43 hybridization signal was significantly higher in the male cortex, bed nucleus, and medial preoptic nucleus, but not the ventromedial and arcuate nuclei, than in postnatal females. Analysis of slide autoradiograms demonstrated that the change in GAP-43 mRNA during postnatal development was due to changes at the cellular level. The present results indicate that expression of GAP-43 mRNA is transiently elevated and sexually dimorphic in certain regions of the early postnatal rat brain. The results further suggest that the differential expression of GAP-43 in the male and female postnatal brain may be related to sex differences in neuronal outgrowth and connectivity resulting in a dimorphism in the pattern of adult neuronal circuitry. PMID- 8201018 TI - Reorganization of visual interneurons during metamorphosis in the swallowtail butterfly Papilio xuthus. AB - The metamorphic fate of larval visual interneurons in the swallowtail butterfly Papilio xuthus has been examined by using reduced silver impregnation and immunocytochemistry of gamma-amino butyric acid (GABA). Visual interneurons in the second larval optic neuropile (medulla) can be followed throughout metamorphosis because of large somata located in the anterior edge of the imaginal medulla. Ten to 12 neurons in the larval medulla were immunoreactive to a GABA-antiserum. They arborize in the larval medulla and extend dendritic processes to the first larval optic neuropile (lamina). After pupation, the medulla neurons lose GABA-immunoreactive larval processes and differentiate new processes that enter tangentially into the developing imaginal medulla. Axons of the surviving larval neurons follow an optic tract between the lobula and the lobula plate and extend to the lateral area of the protocerebrum. Thus, larval visual interneurons are incorporated into the imaginal optic lobe and may play a new role in the visual processing of the butterfly. PMID- 8201019 TI - Inverse patterns of myelination and GAP-43 expression in the adult CNS: neurite growth inhibitors as regulators of neuronal plasticity? AB - In the central nervous system (CNS) myelin is present not only in white matter, but also in varying amounts in many gray matter areas. In addition to the function of electrical insulation of axons, myelin and oligodendrocytes contain molecules that are powerful inhibitors of neurite growth. Nevertheless plastic changes involving sprouting of nerve terminals occur in several brain regions of adult animals after partial lesions. In this study we have tried to correlate the plastic potential of CNS regions with the degree of their myelination. The expression of the growth-associated protein GAP-43 was used as an indicator of the potential for plastic changes, and a histological myelin stain was used to assess myelination. We have found that myelination and GAP-43 expression have strikingly inverse expression patterns in the majority of CNS gray matter areas. Densely myelinated regions, that is, most brainstem nuclei, the tegmentum, and the inferior colliculus, are low in GAP-43. In contrast, unmyelinated or lightly myelinated areas, such as the substantia gelatinosa of the spinal cord, the nucleus of the solitary tract, or the septum, express high levels of GAP-43. Areas known to show lesion-induced sprouting are typically high in GAP-43 and only lightly myelinated. During postnatal development the myelination pattern precedes the GAP-43 pattern, a sequence that is consistent with a role of myelin and the associated neurite growth inhibitors in modifying GAP-43 expression. Our results support the hypothesis that myelin-associated neurite growth inhibitors are involved in regulating the stability of neural connections. PMID- 8201020 TI - Central terminations of low-threshold mechanoreceptive afferents in the trigeminal nuclei interpolaris and caudalis of the cat. AB - Previous studies indicate that vibrissa, nonvibrissa, guard hair, hairy skin, and periodontal ligament afferents give rise to morphologically distinct terminal arbors in the trigeminal nuclei principalis (Vp) and oralis (Vo) in the cat. The present study describes the extent to which morphological and functional relationships exist in the nuclei interpolaris (Vi) and caudalis (Vc). Twenty-two fibers were physiologically characterized and stained by intra-axonal HRP injection techniques. The fast adapting (FA) vibrissa (VF) afferents gave rise to compact and circumscribed arbors in Vi and Vc. These tended to be larger in Vc than in Vi. The slowly adapting (SA) vibrissa (VS) afferents in Vi and Vc had more widespread and larger arbors than those of the VF afferents. The VS arbors in Vc tended to be larger and less circular than those in Vi. Guard hair (GH) afferents gave rise to circumscribed arbors in both nuclei, but those in Vc tended to have larger and more circular arbors than those in Vi. Down hair (DH) afferents gave rise to small, circumscribed arbors or a few distinct patches of boutons within a small area in Vi; arbors in Vc were less extensive and "stringy." Unlike other afferents, DH arbors were larger in Vi than in Vc, but smaller than those of GH afferents in either nuclei. The SA hairy skin (SS) afferents had arbors that were widespread with a few distinct patches of boutons; the arbors in Vc were larger than those in Vi. The arbors of SS afferents were smaller than those of VS and GH afferents in both nuclei. Like GH afferents, FA periodontal ligament (PF) afferents gave rise to large and circumscribed arbors in Vi, although the arbors in Vc were smaller and less dense. The present study demonstrated significant functional and morphological relationships for primary afferents in Vi and Vc, thus suggesting that sensory information from each of the distinct fiber or functional classes is processed in a characteristic manner in the individual nuclei. PMID- 8201021 TI - Behavior-dependent activity labeling in the central complex of Drosophila during controlled visual stimulation. AB - 3H-2-deoxyglucose (2-DG) is used as a histological marker to study the spatial distribution of neuronal activity in the central brain of Drosophila melanogaster under controlled stimulus conditions. Tethered flies injected with the label are kept for 45-90 minutes in the center of a rotating drum carrying on its periphery a single black vertical stripe or a periodic grating. In either stimulus situation, one-half of the flies walk on top of a small black styrofoam ball floating on a jet of air, and one-half are kept flying 1.5 mm above the ball. 1) During walking on the styrofoam ball little 2-DG accumulates in the central brain. The area in and around the ellipsoid body as well as several tracts are weakly labeled. 2) After flight, labeling patterns are more distinct. The following labeled structures can be identified: ventral bodies, ring neurons of the ellipsoid body, the region of the inferior bridge, fiber tracts connecting the central complex to other parts of the protocerebrum, and tracts in the subesophageal and dorsal brain. These contrast with fan-shaped body and protocerebral lobes, which are only weakly labeled. 3) Not only flight and walking lead to distinct staining patterns but also the two visual stimuli. With the single stripe, in most flies the caudal layers of the ellipsoid body accumulate more 2-DG than the rostral ones. With the striped drum, the ellipsoid body is uniformly labeled. 4) Other stimulus-related features are found less regularly: Unilateral distribution of 2-DG in or around the noduli was observed in several flies that had been exposed to a rotating single stripe. In one preparation, two strongly marked individual neurons of the protocerebral bridge can be tentatively identified. The labeling patterns support earlier notions that the central complex is involved in the initiation and organization of behavior and that it integrates visual data of the two brain hemispheres. PMID- 8201022 TI - Expression of the tight junction protein ZO-1 in the olfactory system: presence of ZO-1 on olfactory sensory neurons and glial cells. AB - The olfactory system is a unique part of the central nervous system since it retains neuronal turnover and regenerative capacities in adulthood. Thus it provides an ideal model to study plasticity of membrane moities involved in cell cell interactions. One structure particularly involved in cell-cell interaction is the tight junction, which establishes polarization of epithelial cells and creates diffusion barriers to paracellular passages. ZO-1 is a phosphoprotein peripherally associated with tight junctions. We have studied expression of ZO-1 protein in the developing and adult olfactory system of the mouse in order to get information about the localization and developmental expression of this tight junction component. ZO-1 expression has also been determined in cell cultures of olfactory bulbs. ZO-1 was present in the olfactory placode prior to formation of tight junctions. ZO-1 was localized in the developing and mature olfactory epithelium at heterotypic contacts between supporting cells and olfactory neurons as well as at homotypic contacts between both these cell types. Confocal microscopy showed quantitative differences in the ZO-1 expression among different olfactory dendrites. In the olfactory nerves ZO-1 immunolabeling was detectable between olfactory ensheathing cells. From the seventh postnatal day ZO-1 immunolabeling was detected at the mitral cell layer of the bulb on cells tentatively identified as oligodendrocytes. Myelinated tracts of the bulb were ZO 1 negative. Cell cultures of olfactory bulbs showed ZO-1 immunoreaction, mostly localized on glial fibrillary acidic protein (GFAP)-positive cells. Our results provide further evidence that ZO-1 serves functions unrelated to the tight junction complex and indicate molecular heterogeneity of these cell-cell contacts. PMID- 8201023 TI - In vitro autoradiographic localization of calcitonin binding sites in human medulla oblongata. AB - In this study we examined the distribution of calcitonin (CT) binding sites in the human medulla oblongata by in vitro autoradiography. In competition studies, the rank order of potency for calcitonins competing for 125I-salmon CT binding was salmon CT > porcine CT > human CT, which is consistent with physiologically relevant CT receptors in other systems. For the determination of CT binding in the human medulla, 20-micron cryostat sections were incubated with 125I-salmon CT in the presence or absence of 10(-6) M unlabelled salmon CT to map specific CT binding sites. Punctate binding was observed over discrete nuclei of the medulla. High binding densities were seen over subnuclei of the dorsal motor nucleus of the vagus, the nucleus of the solitary tract, the intermediate reticular zone, the gigantocellular and dorsal paragigantocellular nuclei, and the raphe obscurus nucleus. Moderate levels of binding were observed over the lateral paragigantocellular nucleus and the rostral extent of the epiolivary nucleus. The cuneate and gracile nuclei and the fiber tracts did not contain detectable binding, while the inferior olivary nucleus had moderate levels of nonspecific binding. The localization of calcitonin binding sites in the human presents similarities but also important differences to the distribution in rat and cat. The most notable difference is the extreme binding densities in the intermediate reticular zone of the human. The location of binding sites suggests involvement of calcitonin in regulation of autonomic function. PMID- 8201024 TI - Birthdates of neurons in the retinal ganglion cell layer of the ferret. AB - The present study determined the temporal and spatial patterns of genesis for neurons of different sizes in the retinal ganglion cell layer of the ferret. Fetal ferrets were exposed to tritiated thymidine on embryonic days E-22 through E-36. One to 3 months after birth, they were perfused and their retinae dissected, and autoradiographs were prepared from resin-embedded sections throughout the entire flattened retinal ganglion cell layer. Soma size differences in conjunction with separate retrograde labeling and calbindin immunocytochemical studies were used as criteria for identifying different retinal ganglion cell subtypes in juvenile and adult ferrets. Neurons of different sizes in the ganglion cell layer were generated at different stages during development. Medium sized cells were generated primarily between E-22 and E-26; the largest cells were generated between E-24 and E-29; small cells were generated between E-26 and E-32; and very small cells were generated between E-29 and E-36. The former three groups were interpreted to be three subtypes of retinal ganglion cells, while the latter group was interpreted to be displaced amacrine cells. This temporal order of the genesis of ganglion cell classes is consistent with the spatial ordering of their fibers in the mature optic chiasm and tract, and it is consistent with the developmental change in decussation pattern recently shown in the optic pathway of embryonic ferrets. The spatial pattern of genesis suggests that ganglion cells of a particular class are added to the ganglion cell layer in a centroperipheral fashion initiated in the dorsocentral retina nasal to the area centralis. No evidence was found for a wave of ganglion cell addition that proceeded in a spiralling pattern around the area centralis, as has been reported in the cat. PMID- 8201025 TI - Noradrenergic innervation of vasopressin- and oxytocin-containing neurons in the hypothalamic paraventricular nucleus of the macaque monkey: quantitative analysis using double-label immunohistochemistry and confocal laser microscopy. AB - Previous reports on the rat and monkey hypothalamus have revealed a dense noradrenergic innervation within the hypothalamic paraventricular nucleus as assessed by dopamine-beta-hydroxylase immunohistochemistry. These single-label analyses were unable to delineate the cellular structures which receive this catecholaminergic innervation. Double-label preparations in the rat hypothalamic paraventricular nucleus have demonstrated synaptic interactions between noradrenergic varicosities and magnocellular neurons. However, the density and distribution of varicosities contacting chemically identified magnocellular neurons have not been assessed at the light or electron microscopic level. In this report, single-label immunohistochemistry was used to assess the morphology and distribution of vasopressin- and oxytocin-immunoreactive neurons within the macaque hypothalamic paraventricular nucleus. In addition, double-label immunohistochemistry was combined with confocal laser scanning microscopy to quantify the number of dopamine-beta-hydroxylase-immunoreactive varicosities in apposition to magnocellular neurons expressing vasopressin or oxytocin immunoreactivity. The morphology of chemically identified neurons was also compared to magnocellular neurons in the monkey hypothalamic paraventricular nucleus which were filled with Lucifer Yellow in order to assess the somatodendritic labeling of the immunohistochemical preparation. Qualitative assessment of immunohistochemically identified magnocellular cells indicated that vasopressin- and oxytocin-containing neurons are observed throughout the rostrocaudal extent of the monkey hypothalamic paraventricular nucleus, demarcating this structure from the surrounding anterior hypothalamus. The distribution of the two nonapeptides is complementary, with vasopressin immunoreactive neurons having a greater somal volume and located in a more medial aspect of the mid and caudal hypothalamic paraventricular nucleus relative to oxytocin-immunoreactive perikarya. For the double-label preparations, a series of confocal optical sections was assessed through the total somal volume of vasopressin- and oxytocin-immunoreactive neurons along with the corresponding dopamine-beta-hydroxylase-immunoreactive varicosities in the same volume of tissue, generating a varicosity-to-neuron ratio which was further characterized morphologically to assess afferent input to the soma and proximal dendrites. Quantitative analysis revealed that vasopressin-immunoreactive neurons received approximately two thirds of their dopamine-beta-hydroxylase-immunoreactive varicosities in apposition to the proximal dendrites and one third in apposition to the somata. Furthermore, vasopressin-immunoreactive neurons received a greater innervation density than oxytocin-immunoreactive neurons, which did not have a differential distribution of varicosities on the proximal dendrites and somata. The distribution of dopamine-beta-hydroxylase-immunoreactive afferents on magnocellular neurons in the hypothalamic paraventricular nucleus may reflect a physiological role of this circuit in terms of preferential release of vasopressin from magnocellular neurons upon noradrenergic stimulation. PMID- 8201026 TI - Nerve growth factor-like immunoreactive profiles in the primate basal forebrain and hippocampal formation. AB - The distribution of nerve growth factor (NGF), the prototypic neurotropin, within the basal forebrain and hippocampal formation of young adult monkeys and aged humans was characterized with an affinity purified polyclonal beta-NGF antibody raised against mouse beta-NGF. In the basal forebrain of both primates, a granular NGF-like immunoreactive (ir) reaction product was observed within neurons of the medial septum, nucleus of the diagonal band, and nucleus basalis of Meynert. NGF-like immunoreactivity exclusively colocalized within p75 NGF receptor (NGFR) containing basal forebrain neurons. The intensity of NGF immunolabeling varied between cell bodies. Many NGF-ir perikarya were highly immunoreactive. In other basal forebrain neurons, NGF-like immunoreactivity was either undetectable or minimally expressed. In the hippocampus of both species, NGF-like immunoreactivity was mainly localized within the hilus of the dentate gyrus and within CA3 and CA2 hippocampal subfields. A marked diminution in NGF like staining was seen in CA1. Within the hippocampal formation, NGF-like immunoreactivity was heaviest within the neuropil of stratum radiatum, intermediate in stratum oriens, and lightest in stratum pyramidal. NGF-like immunoreactivity was not found within the granule or pyramidal cells of the dentate gyrus and hippocampal formation, respectively. These findings demonstrate the presence of an NGF-like antigen in association with monkey and human magnocellular basal forebrain neurons and within their hippocampal target sites. This lends support to the hypothesis that NGF is internalized from sources located within target regions of the primate cholinergic basal forebrain neurons and is retrogradely transported to these cell bodies where the NGF trophic effect likely occurs. PMID- 8201027 TI - Parvalbumin, calbindin D-28k, and calretinin immunoreactivity in the ascending auditory pathway of horseshoe bats. AB - In the subcortical auditory system of Rhinolophus rouxi, antibodies directed against the calcium-binding proteins parvalbumin, calbindin D-28k, and calretinin yield partly overlapping and partly complementary labeling patterns which are described in detail for each nucleus. The most general features of the labeling patterns are that: 1) Parvalbumin is a potent marker for large and heterogeneous populations of cells and puncta (presumed axon terminals) throughout the auditory pathway. 2) Immunostaining with the monoclonal calbindin-antiserum was typically absent or sparse in most auditory brainstem centers, but prominent in auditory nerve fibers and in cells of the medial geniculate body (MGB). 3) Calretinin label is abundant but more restricted to subsets of auditory nuclei or subpopulations of cells than parvalbumin. 4) Calcium-binding proteins are useful markers to define particular subregions or cell types in auditory nuclei: for example, i) different labeling patterns are obtained within the nuclei of the lateral lemniscus and adjacent tegmental zones; ii) in the inferior colliculus both calbindin- and calretinin-antisera yield similar regional specific staining patterns, but label different cell types; iii) subregions of the medial geniculate body have characteristic profiles of calcium-binding proteins; and iv) analyses of different nuclei showed that there is no simple common denominator for cells characterized by the expression of particular calcium-binding proteins, nor does labeling correspond in a straightforward way with specific functional systems. 5) there are profound differences between the calbindin labeling patterns seen in Rhinolophus and those in other mammals. PMID- 8201028 TI - Immunocytochemical localisation of hydroxyindole-O-methyltransferase in pineal photoreceptor cells of several fish species. AB - Melatonin is an internal "Zeitgeber," involved in the timing and control of a number of rhythmic functions and behaviours. Its synthesising cells remain to be identified in the fish pineal. The last step in the melatonin biosynthetic pathway is catalysed by the enzyme hydroxyindole-O-methyltransferase. An affinity purified antibody, directed against chicken pineal hydroxyindole-O methyltransferase, was used in the present study to identify the melatonin synthesising cells in four fish species: a primitive chondrostean (sturgeon), a saltwater teleost (dorado), and two freshwater teleosts (pike, trout). Western blot immunolabeling of pike and trout pineal proteins revealed a single band at 38 KDa, which corresponds to the known molecular weight of the enzyme in bovine, rat, and chicken pineal. Regardless of the species, a specific immunocytochemical labeling, visualised by means of the peroxidase-antiperoxidase method, was exclusively associated with the photoreceptor cells. These results provide evidence that photoreceptors of the fish pineal are responsible for the biosynthesis of 5-methoxyindoles, including melatonin. In the pike, reactions were less intense in the distal portion of the pineal vesicle than in the other regions of the organ. It is questioned whether this might be related to the existence of a germinative zone, generating new photoreceptor cells in this distal portion. Hydroxyindole-O-methyltransferase has been previously demonstrated in mammalian pinealocytes, and modified photoreceptors of the avian pineal. It is now demonstrated in pineal photoreceptors of a primitive fish and of more evolved saltwater and freshwater fish. The results strengthen the view that these cells are related through phylogeny and that their well conserved melatoninergic function appears early in the course of evolution. PMID- 8201030 TI - Antibody to neural cell adhesion molecule can disrupt the migration of luteinizing hormone-releasing hormone neurons into the mouse brain. AB - The neurons which synthesize and release luteinizing hormone-releasing hormone (LHRH), are hypothesized to originate in the epithelium of the medial olfactory pit and to migrate into the brain along a scaffolding made up of neural cell adhesion molecule (NCAM)-immunoreactive branches of the terminal and vomeronasal nerves. These LHRH neurons, studied by immunocytochemical and autoradiographic procedures, were found to originate within a very short period of embryogenesis, specifically day 10, in mice, and to follow a remarkably ordered spatiotemporal course along the migration route into the brain. The purpose of the present experiments was to determine whether perturbation of the NCAM-immunoreactive migration route, at a particular time in development, would arrest the migration of LHRH neurons into the brain. We found that a 1 microliter injection of antiserum to NCAM into the area of the olfactory pit, on day 10 of embryogenesis, significantly reduced the number of LHRH-immunoreactive neurons seen in the epithelium of the medial olfactory pit, with a concomitant significant reduction in the number of LHRH-immunoreactive cells seen outside of the placode, on the migration route. These results confirm our initial hypothesis that LHRH neurons migrate from the epithelium of the olfactory pit to the brain and indicate that NCAM plays a causal role in this phenomenon. PMID- 8201029 TI - Expression of the gene for the neuronal intermediate filament protein alpha internexin coincides with the onset of neuronal differentiation in the developing rat nervous system. AB - While neurofilaments have long been considered early markers of neuronal differentiation, they cannot be detected in most newly postmitotic neurons of the developing central nervous system (CNS). Here we show that these neurons already express the neuronal intermediate filament protein alpha-internexin at high levels. alpha-internexin is expressed by most, if not all, neurons as they begin differentiation and shows no overlap with vimentin, whose expression in the CNS is restricted to mitotic neuronal precursors. In the adult, alpha-internexin is the only intermediate filament gene expressed by the cerebellar granule cells, the source of the thin-caliber parallel fibers; conversely, neurofilament proteins are highly expressed in large neurons, which express alpha-internexin at low levels. These data suggest that neuronal intermediate filaments may regulate axonal stability and/or diameter through changes not only in their number, but also in their subunit composition. PMID- 8201031 TI - Distribution of VIP mRNA and two distinct VIP binding sites in the developing rat brain: relation to ontogenic events. AB - The peptide neurotransmitter vasoactive intestinal peptide (VIP) has neurotrophic properties and influences neurobehavioral development. To assess the role of VIP during neural ontogeny, the present work traces the development of VIP mRNA with in situ hybridization and VIP receptors with in vitro autoradiography in rat central nervous system (CNS) from embryonic day 14 (E14) to the adult. VIP mRNA was not evident in the CNS until birth. Postnatally, it was expressed in several distinct brain regions, but its distribution bore little relation to that of VIP receptors. VIP receptors were present and expressed changing patterns of distribution throughout CNS development. The changing patterns were the result of 1) the transient appearance of GTP-insensitive VIP receptors in several regions undergoing mitosis or glial fasciculation and 2) the transient appearance of GTP sensitive VIP receptors homogeneously distributed throughout the CNS during the first 2 postnatal weeks, the period of the brain growth spurt. At E14-16 VIP binding was dense throughout the brainstem and spinal cord, but limited in the rest of the brain. From E19 to postnatal day 14 (P14), while VIP binding was higher in germinal zones, it tended to be uniformly dense throughout the remainder of the brain. By P21 the adult pattern began to emerge; VIP binding was unevenly distributed and was related to specific cytoarchitectural sites. Since the expression of VIP in the CNS is limited to postnatal development but VIP receptors are abundant prenatally, we suggest that extraembryonic VIP may act upon prenatal VIP receptors to regulate ontogenic events in the brain. PMID- 8201032 TI - Morphology of parallel fibres in the cerebellar cortex of the rat: an experimental light and electron microscopic study with biocytin. AB - Microinjections of biocytin have been made in the granular layer of the rat cerebellar cortex in order to label the axonal projections of a localised population of granule cells. Light microscopic techniques were used to determine the lengths of the parallel fibres and to measure the spacing and size of the fibre varicosities. Fibres were longest in the superficial one-third of the molecular layer, where mean overall length was 4.7 mm, and mean length decreased to 4.2 mm in the lower one-third of the molecular layer. We found no very short fibres but a small population deep in the molecular layer had a branch length of about one-half the average. Mean intervaricosity interval and varicosity size varied with distance from proximal to distal along the fibres. Mean intervaricosity interval was 3.7 microns within 250 microns of the fibre bifurcation points and progressively increased towards the distal ends, where the mean interval was 7.4 microns. Mean varicosity size was 0.82 microns 2 in this proximal region and decreased to 0.47 microns 2 about 1.2 mm distally. Mean intervaricosity interval on the ascending axons of the granule cells was 4.0 microns. Electron microscopy revealed that a high proportion (89%) of the parallel fibre varicosities formed synaptic junctions. The majority of the synapses (91%) were formed on Purkinje cell dendritic spines. Some varicosities also formed simultaneous synaptic contacts or double synapses with two spines. These double synapses occurred more frequently in the proximal region of the fibres (11%) than on the distal ends (2%). The length of the postsynaptic density also differed according to the location of the varicosities and the mean length at the proximal parallel fibre synapses was 0.59 microns compared with 0.38 microns at the distal synapses. It is concluded that a beam or bundle of parallel fibres originating from cells in a focal region of the granular layer will exert a graded synaptic influence on its target Purkinje cells, with the most powerful influence occurring on cells located around the proximal region of the fibres where they bifurcate and the weakest action being exerted on cells located at the distal end of the fibres. PMID- 8201033 TI - Development of interneurons with ipsilateral projections in embryonic rat spinal cord. AB - Considerable progress has been made in recent years in identifying molecules with restricted expression in mammalian spinal cord at early developmental stages. However, the significance of the different expression patterns for most of these molecules is unclear because so little is known about the development of various classes of spinal interneurons. Recently, we have characterized the development of rat spinal cord interneurons with an axon that crosses in the ventral commissure (Silos-Santiago and Snider, J. Comp. Neurol., 325:514, 1992). In the current study, we describe the morphological development of ipsilaterally projecting spinal interneurons in laminae V-VIII of the thoracic spinal cord. These neurons were labelled by retrograde lateral diffusion of DiI after crystals were placed in various locations in the embryonic thoracic cord. By E14, approximately 48 hours after the first interneurons are generated, eight different groups of ipsilateral interneurons are present in the spinal cord. By E15, these groups of ipsilateral interneurons have reached distinct locations within the gray matter. Even at this early stage, different groups of cells have elaborated characteristic dendritic arborizations. By E19, at least 17 different types of ipsilateral interneurons can be identified on the basis of location and dendritic morphology. In general, ipsilateral interneurons are located more dorsally and laterally than commissural interneurons at all stages of embryonic development. Furthermore, in comparison with commissural neurons, fewer ipsilateral interneurons have dendritic arbors with a mediolateral orientation in the transverse plane. This work demonstrates that rat embryonic spinal cord contains a large number of morphologically distinct classes of interneurons that extend axons into the ipsilateral lateral funiculus. These neurons can be distinguished from commissural neurons on the basis of location and morphology. These results, taken together with those from our previous study, provide a framework for the localization of gene expression to different classes of spinal interneurons at early developmental stages. PMID- 8201034 TI - Persistence of rubrospinal projections following spinal cord injury in the rat. AB - Recent neurophysiological and magnetic resonance imaging studies of clinically "complete" human spinal cord injuries indicate that some patients have considerable subclinical function and substantial morphological integrity of descending spinal tracts. In contrast, extensive histopathological changes, including cell death, have been described in central nervous system nuclei projecting to the cord following experimental transection or hemisection of the spinal cord in animal models. We have used a rodent model of severe compression cord injury that more closely resembles the clinical pathophysiology to investigate the extent of the persistence of the rubrospinal projection. Counts of red nucleus neurons retrogradely labelled with Fluorogold demonstrate that in contrast to the results obtained with transection models, compression injuries of the spinal cord do not result in massive loss of rubrospinal projections, at least up to 8 weeks postinjury. The results also suggest that many of the axons persist distal to the lesion site and that they are functionally intact with respect to retrograde transport capabilities. PMID- 8201035 TI - Peripheral innervation patterns of vestibular nerve afferents in the bullfrog utriculus. AB - Vestibular nerve afferents innervating the bullfrog utriculus differ in their response dynamics and sensitivity to natural stimulation. They also supply hair cells that differ markedly in hair bundle morphology. To examine the peripheral innervation patterns of individual utricular afferents more closely, afferent fibers were labeled by the extracellular injection of horseradish peroxidase (HRP) into the vestibular nerve after sectioning the vestibular nerve medial to Scarpa's ganglion to allow the degeneration of sympathetic and efferent fibers. The peripheral arborizations of individual afferents were then correlated with the diameters of their parent axons, the regions of the macula they innervate, and the number and type of hair cells they supply. The utriculus is divided by the striola, a narrow zone of distinctive morphology, into medial and lateral parts. Utricular afferents were classified as striolar or extrastriolar according to the epithelial entrance of their parent axons and the location of their terminal fields. In general, striolar afferents had thicker parent axons, fewer subepithelial bifurcations, larger terminal fields, and more synaptic endings than afferents in extrastriolar regions. Afferents in a juxtastriolar zone, immediately adjacent to the medial striola, had innervation patterns transitional between those in the striola and more peripheral parts of the medial extrastriola. Most afferents innervated only a single macular zone. The terminal fields of striolar afferents, with the notable exception of a few afferents with thin parent axons, were generally confined to one side of the striola. Hair cells in the bullfrog utriculus have previously been classified into four types based on hair bundle morphology (Lewis and Li: Brain Res. 83:35-50, 1975). Afferents in the extrastriolar and juxtastriolar zones largely or exclusively innervated Type B hair cells, the predominant hair cell type in the utricular macula. Striolar afferents supplied a mixture of four hair cell types, but largely contacted Type B and Type C hair cells, particularly on the outer rows of the medial striola. Afferents supplying more central striolar regions innervated fewer Type B and large numbers of Type E and Type F hair cells. Striolar afferents with thin parent axons largely supplied Type E hair cells with bulbed kinocilia in the innermost striolar rows. PMID- 8201036 TI - Efferent connections from the lateral hypothalamic region and the lateral preoptic area to the hypothalamic paraventricular nucleus of the rat. AB - The lateral preoptic and lateral hypothalamic regions contain the majority of the cell groups embedded in the fibre trajectories of the medial forebrain bundle on its course through the hypothalamus. Recent studies have extended considerably the parcellation of the lateral hypothalamic region, and therefore, the need to emphasize new insights into the anatomical organisation of projections from the neurons of the lateral hypothalamic region. In the present study we describe the anatomical organisation of efferent projections from the lateral preoptic and lateral hypothalamic regions to the hypothalamic paraventricular nucleus (PVN) on the basis of retrograde- and anterograde-tracing techniques. Iontophoretic injections of the retrograde tracer, cholera toxin subunit B, into the PVN revealed that most hypothalamic nuclei project to the PVN. Within the lateral hypothalamic region, retrogradely labelled cells were concentrated in the intermediate hypothalamic area, the lateral hypothalamic area, and the perifornical nucleus, whereas fewer retrogradely labelled cells were found in the lateral preoptic area. To determine the distribution of terminating fibres in subnuclei of the heterogeneous PVN, iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin were delivered into distinct areas of the lateral hypothalamic region. Neurons of the intermediate hypothalamic area projected mainly to the PVN subnuclei, which contained parvicellular neuroendocrine cells. In contrast, neurons of the rostral and tuberal parts of the lateral hypothalamic area and the perifornical nucleus projected to the PVN subnuclei, which contained parvicellular neurons that send descending projections to preganglionic cell groups in the medulla and spinal cord. The perifornical nucleus was the only area within the lateral hypothalamic region that consistently innervated magnocellular perikarya of the PVN. Finally, all areas of the lateral hypothalamic region contributed substantially to fibres terminating in the perinuclear shell of the PVN. These results demonstrate that anatomically distinct areas of the lateral hypothalamic region have distinct projections to subnuclei of the PVN and further substantiate the view that the lateral hypothalamic region as well as the PVN constitute anatomically and functionally heterogeneous structures. PMID- 8201037 TI - Compressed baled alfalfa hay for primiparous and multiparous dairy cows. AB - Compressed baled alfalfa hay was fed to cows, and the effects on productivity, chewing activities, and digestion were measured using a replicated 4 x 4 Latin square design. Cows received second-cutting alfalfa hay (20% CP; 40% NDF) from either compressed or standard small rectangular bales at two forage to concentrate ratios (35:65 and 65:35, DM basis). Compressed hay did not affect milk yield, although milk fat content was higher (2.90 vs. 2.68%). Higher concentrate diets increased milk yield (32.2 vs. 28.3 kg/d), lowered milk fat (2.66 vs. 2.91%), and increased milk protein (3.16 vs. 2.99%) and lactose (5.06 vs. 4.99%) with no interaction between concentrate proportion and hay type. Cows fed compressed bales spent less time eating per kilogram of DM and NDF consumed than cows fed standard bales, but rumination time was unaffected by forage processing. For cows fed both types of hay, digestibilities of DM, ADF, and NDF were similar; ruminal liquid outflow rates also were similar, but rate of particulate passage from the reticulo-rumen was greater for cows receiving compressed hay. Compressing alfalfa hay did not adversely affect forage quality but increased the ease of shipping and handling and minimized storage space requirements. This process may be beneficial when higher milk fat content is desirable or when cows have limited time to consume forage. PMID- 8201038 TI - Optimal neutral detergent fiber concentration of barley-based diets for lactating dairy cows. AB - Twelve lactating, multiparous Holstein cows were used in two experiments, designed as 6 x 6 Latin squares with 28-d periods, to evaluate the effects of increasing the NDF concentration of diets consisting of barley-based concentrates and various forages. Diets were designed in a 3 x 2 factorial set with three concentrations of total dietary NDF (32, 36, and 40%) combined with two sources of forage. In Experiment 1, cows received alfalfa hay (45.1% NDF) or orchardgrass hay (54.0% NDF). In Experiment 2, cows received alfalfa hay (42.5% NDF) or corn silage (50.5% NDF). Cows ate more DM when fed alfalfa hay than when fed orchardgrass hay or corn silage. Intake of DM decreased as NDF concentration increased for alfalfa hay and corn silage diets, but a positive quadratic relationship between DMI and NDF occurred for orchardgrass hay. As dietary NDF increased, milk yield decreased, but fat percentage increased. Time spent ruminating was associated positively with concentration of NDF and was similar for diets formulated with various forages at the same dietary NDF concentration. Regardless of forage source, increasing dietary NDF concentration did not affect FCM yields because, as NDF intake increased, energy intake decreased. With consumer demand for low fat milk products, high yield of low fat milk is advantageous, and the minimal amount of fiber necessary in dairy cattle diets may be less than currently recommended. Further research is required to determine the long-term effects on health and longevity of low fiber diets fed to cows. PMID- 8201039 TI - Effect of steam flaking of corn and sorghum grains on performance of lactating cows. AB - The objective of this study was to compare the relative feeding value of sorghum versus corn grain in rolled or steam-flaked forms in diets for lactating dairy cows. Twenty-four Holstein cows (averaging 110 DIM) were divided into four groups and fed diets of 40% grain as dry-rolled sorghum, steam-rolled corn, steam-flaked sorghum, or steam-flaked corn for 70 d. Compared with rolling, flaking of both grains increased yields of milk, milk protein and fat, and protein percentage of milk, but differences tended to be greater for sorghum than for corn. Efficiency of feed utilization was higher for steam-flaked than for dry-rolled sorghum but was unaffected by corn processing. Flaking of both grains increased total tract digestibilities of DM, OM, CP, starch, ADF, and NDF. Estimates for NEL were 21% higher for flaked than for rolled sorghum and 6% higher for flaked than for rolled corn. No differences in performance of cows existed between corn and sorghum grains. Cows fed 40% of their diet as steam-flaked sorghum or corn yielded more milk and milk protein than those fed the rolled form of the grains, and no differences existed between types of grain fed. PMID- 8201040 TI - Comparison of sorghum and corn grains in early and midlactation diets for dairy cows. AB - Two trials were conducted to compare the effects of corn and sorghum grains on performance of early and midlactation Holstein dairy cows. In trial 1, 36 multiparous midlactation cows were assigned to one of four diets in a 2 x 2 factorial arrangement for 10 wk: 1) grain mixture containing 77% rolled corn fed in a TMR, 2) same grain fed separately from forage, 3) grain mixture containing 77% finely ground sorghum fed in a TMR, and 4) same grain fed separately from forage. Grain source and feeding methods had similar effects on milk yield, milk fat percentage, SNF, SCM, and BW. Cows fed sorghum had higher DMI; cows fed corn had greater efficiency of milk yield. In trial 2, 36 multiparous early lactation cows were assigned to one of four TMR in a 2 x 2 factorial arrangement for 9 wk: 1) TMR containing 35.5% rolled corn, 2) TMR containing 35.5% finely ground corn, 3) TMR containing 35.5% rolled sorghum, and 4) TMR containing 35.5% finely ground sorghum. Grain source produced no differences in DMI, milk yield, milk fat percentage, SCM, and BW. Cows fed finely ground grain yielded more milk than those fed rolled grain. Finely ground sorghum promoted higher milk protein and SNF percentages than did finely ground corn. Total tract starch digestibility was greater for corn than for sorghum. These two trials indicate that sorghum grain, when finely ground, supports milk yield and composition similar to that of corn. PMID- 8201041 TI - Infusion of four long-chain fatty acid mixtures into the abomasum of lactating dairy cows. AB - Five Holstein cows were utilized in a Latin square design to determine the effects of postruminal profile of fatty acids on DMI, milk yield and composition, nutrient digestibilities, and metabolites in blood. Treatments were abomasal infusions of 1) control, 169 to 180 g/d of meat solubles; 2) control plus 450 g/d of mostly saturated fatty acids; 3) canola fatty acids; 4) soybean fatty acids; or 5) sunflower fatty acids. Infusion of fatty acids decreased intakes of DM, CP, and gross energy; yields of milk, FCM, SNF, total solids, CP, NPN, true protein, whey protein, and casein; and percentages of SNF, CP, NPN, true protein, and casein in milk. Cows infused with mostly saturated fatty acids consumed more CP and digestible energy; yielded more milk, FCM, fat, SNF, total solids, CP, true protein, and casein; and had greater percentages of SNF and total solids in milk than cows infused with unsaturated fatty acids. Milk fatty acids reflected the profile of the infused fatty acid mixture. Ruminal characteristics and apparent digestibilities of DM, NDF, energy, and fatty acids generally were not different among treatments. The profile of fatty acids reaching the small intestine may influence responses when supplemental fats are fed to lactating dairy cows. PMID- 8201042 TI - Effects of soybean hulls and lignosulfonate-treated soybean meal on ruminal fermentation in lactating dairy cows. AB - Four Holstein cows were used in a 4 x 4 Latin square design to investigate the effects of soybean hulls and lignosulfonate-treated soybean meal on ruminal fermentation and nutrient passage to the duodenum. Diets contained 32% corn silage, 19.8% alfalfa-grass hay, and 48.2% concentrate (DM basis). Treatments, arranged in a 2 x 2 factorial, were concentrate mixes based on 1) corn and soybean meal, 2) corn and treated soybean meal, 3) soybean hulls and soybean meal, and 4) soybean hulls and treated soybean meal. Individual protein supplements supplied 40% of dietary CP, and corn or soybean hulls constituted 28% of dietary DM. Intake of OM (mean 18.9 kg/d) was similar among treatments, but intake of NDF was 42% greater, and intake of nonstructural carbohydrate was 55% less, for cows fed soybean hulls. Passage of OM to the duodenum was similar among diets, but flow of NDF was 43% greater, and flow of nonstructural carbohydrate was 56% less, for cows fed soybean hulls. Ruminal pH was similar, but total concentrations of VFA increased 7% when soybean hulls replaced corn. Ruminal digestion of dietary CP was 15% less for cows fed treated soybean meal, but bacterial N flows were similar among treatments. Soybean hulls were digested to a similar extent as corn, but few interactions occurred between supplemental carbohydrate and protein sources. PMID- 8201043 TI - Effects of intraperitoneal L-leucine, L-isoleucine, L-valine, and L-arginine on milk fat depression in early lactation cows. AB - Eight Holstein cows were assigned following calving to two groups, balanced for parity, using a continuous completely randomized block design. Cows were fed a diet with 13.5% CP and 22.4% ADF from 35 to 55 DIM and then 13.8% CP and 15% ADF from 56 to 92 DIM. Alfalfa grass hay was the forage source, and concentrate mixtures contained primarily corn and soybean meal. Cows were given daily intraperitoneal infusions of a solution of L-Leu (46.1 g, 84.2 mM), L-Ile (31.4 g, 57.3 mM), L-Val (38.3 g, 78.2 mM), and L-Arg (25.0 g, 34.4 mM) or physiological saline following the a.m. milking from 42 through 84 DIM. Infusion of AA significantly increased plasma concentrations of Leu, Ile, Val, and Arg. Effects of AA infusion occurred during the low fiber period. Cows receiving AA maintained daily milk fat yield, increased p.m. milk fat yield, decreased less in p.m. milk fat percentage, and increased daily and p.m. yields of C16 fatty acids in milk. During the posttreatment period, cows previously receiving AA declined in daily milk fat yield, milk fat percentage, and total daily C4 to C16 milk fatty acid yield. Results suggest that the infused AA may have increased de novo synthesis of C16 milk fatty acids. PMID- 8201044 TI - Electrophoretic analysis of ruminal degradability of corn proteins. AB - Albumin, globulin, and prolamin fractions were extracted from corn meal in water, .5 M NaCl, and 50% (vol/vol) 1-propanol and examined by SDS-PAGE and densitometric scanning to investigate fractional degradation rates of corn proteins. Several protein fractions were identified for globulins, zein prolamins, and glutelins. Ruminal degradability of individual subfractions was evaluated by suspension of corn and corn gluten meal samples in the rumen of lactating dairy cows from 0 to 72 h. Electrophoretic and densitometric analysis of protein residues revealed that the prolamin fraction zein for corn and corn gluten meal was more resistant to ruminal degradation than albumins, globulins, and glutelins. Relative rates of degradation of zein and the fraction containing albumins, globulins, and glutelins were .060, .026, and .018, .015/h for corn and corn gluten meal, respectively. Total degradabilities of corn and corn gluten meal, measured by summation of degradability of subfractional components, were 52.2 and 18.6%. Quantitative measurement of ruminally degradable subfractions and estimation of their degradation rates by electrophoretic and densitometric scanning are useful in understanding ruminal degradability of corn proteins. PMID- 8201045 TI - Total and ionized calcium in parturient dairy cows and their calves. AB - Ionized Ca in blood, standard ionized Ca, pH, and total Ca in plasma were measured in 33 Holstein-Friesian dairy cows and their calves. Blood was taken immediately postpartum and at 12, 24, 48, and 72 h after calving. Cows and their calves were grouped according to parity. Concentrations of ionized and total Ca consistently were higher in neonates than in the dams. Parity differences were significant for maternal ionized Ca and total Ca. However, parity was not significant for ionized or total Ca in the blood of corresponding calves. Changes in ionized Ca concentration in calves of first lactation cows largely were attributable to perinatal acidosis. In contrast to total Ca concentrations, the ionized Ca and standard ionized Ca concentrations in dams and calves were relatively stable throughout the study, suggesting that ionized Ca concentration in blood is indicative of the Ca status of the dairy animal. PMID- 8201046 TI - Additive and nonadditive genetic variances for milk yield, fertility, and lifetime performance traits of dairy cattle. AB - Additive and nonadditive genetic variances were estimated for yield traits and fertility for three subsequent lactations and for lifetime performance traits of purebred and crossbred dairy cattle populations. Traits were milk yield, energy corrected milk yield, fat percentage, protein percentage, calving interval, length of productive life, and lifetime FCM of purebred Simmental, Simmental including crossbreds, and Braunvieh crossed with Brown Swiss. Data files ranged from 66,740 to 375,093 records. An approach based on pedigree information for sire and maternal grandsire was used and included additive, dominance, and additive by additive genetic effects. Variances were estimated using the tildehat approximation to REML. Heritability estimated without nonadditive effects in the model was overestimated, particularly in presence of additive by additive variance. Dominance variance was important for most traits; for the lifetime performance traits, dominance was clearly higher than additive variance. Additive by additive variance was very high for milk yield and energy-corrected milk yield, especially for data including crossbreds. Effect of inbreeding was low in most cases. Inclusion of nonadditive effects in genetic evaluation models might improve estimation of additive effects and may require consideration for dairy cattle breeding programs. PMID- 8201047 TI - A simple procedure for obtaining approximate interim cow solutions from an animal model. AB - The computational costs required for solving the equations for an individual animal mixed model can be considerable. More frequent evaluations would benefit dairy producers, allowing them to make breeding and management decisions earlier. A procedure was developed to immediately obtain approximate estimates of cow breeding value as soon as new information becomes available. Only solutions for cows with records in progress are updated. The algorithm is based on solving a system of two equations and can be applied by producers. The method corrects for changes in estimated production of the current record of a cow but assumes that the effects of changes in evaluations of other animals related to this cow on the evaluation of the cow in question are negligible. Herd-year-season effects are not reestimated. The correlations between the updated cow evaluations based on animal model evaluations computed during May 1992, but using estimated production from November 1992, for records in progress and the animal model evaluations from November were .027 to .064 higher than the correlations between the May and November evaluations for production of milk, fat, and protein. Although gains are slight, the cost application of the algorithm is insignificant. PMID- 8201048 TI - Evaluation of a prototype on-line electrical conductivity system for detection of subclinical mastitis. AB - A prototype on-line system for measurement of electrical conductivity of quarter milk was evaluated for accuracy in detection of subclinical mastitis compared with that of bacteriological culture and SCC of sampled quarters. Because of the low quarter prevalence of mastitis, quarters were sampled conditionally from the signals of the on-line system. All signaled quarters and a random selection of the nonsignaled quarters were sampled. To calculate sensitivity and specificity, the total number of non-signaled quarters was extrapolated. The system identified correctly 18 out of 23 subclinical quarters and 521 out of 555 healthy quarters. Quarter prevalence was about 1%. Predictive value of a positive test (35%) and the predictive value of a negative test (99%) were calculated, as well as sensitivity (25%) and specificity (99%), after extrapolation of the total number of nonsignaled quarters. Because of repeated measurements, sensitivity may be underestimated. When signaled quarters were defined by repeated signals within 14 d, predictive value positive increased to 48%. The prototype on-line system did not detect subclinical mastitis very accurately because of suboptimal test characteristics. PMID- 8201049 TI - Genetic prediction for calving ease in the United States: data, models, and use by the dairy industry. AB - Dystocia of Holsteins has a major economic impact on the dairy cattle industry. Genetic evaluation of AI sires for calving ease is sponsored by the National Association of Animal Breeders. The AI organizations and dairy records processing centers collect data from herds that have progeny of AI bulls. Genetic predictions of merit for calving ease have been available for Holstein AI bulls in the US since 1978. A threshold model was implemented during 1988. The threshold model adjusts for the effects of herd-year, season, sex of calf, parity, and birth-year group of sire to predict the genetic merit of each sire for calving ease. Pedigree information from sires, sons, and grandsons is also included in the analysis to improve the reliability of genetic predictions for bulls that have pedigree data available. Each sire's genetic prediction for calving ease is reported as the expected percentage of difficult births of primiparous cows. National in scope, genetic predictions for calving ease are used internationally by breeders of dairy cattle to minimize the risk of difficult births of primiparous cows and to increase the use of AI for young cows. PMID- 8201050 TI - Antihypertensive effect of the peptides derived from casein by an extracellular proteinase from Lactobacillus helveticus CP790. AB - Peptides derived from alpha s1- and beta-caseins by the Lactobacillus helveticus CP790 proteinase were investigated for their inhibitory activities against angiotensin I-converting enzyme. The antihypertensive effect of casein hydrolysates in strain SHR spontaneously hypertensive rats was also investigated. Both alpha s1- and beta-casein hydrolysates inhibited this enzyme. Some of these peptides showed enzyme inhibitory activity, and one of them from beta-casein inhibited the enzyme greatly; the concentration of an angiotensin I-converting enzyme inhibitor needed to inhibit 50% of the enzyme activity was 4 microM. The hydrolysate of casein demonstrated antihypertensive activity in spontaneously hypertensive rats at an orally administered dosage of 15 mg/kg of body weight. MILK fermented with L. helveticus CP790, containing about .3% peptides, also showed antihypertensive activity in SHR rats with 5 ml/kg of body weight (15 mg of peptide/kg); however, the milk fermented with L. helveticus CP791, a variant defective for proteinase activity, did not show this activity. Results suggested that the peptides liberated from casein by the proteinase in the culture medium showed antihypertensive effect in SHR rats. PMID- 8201052 TI - Determination of cadmium and lead in raw milk by graphite furnace atomic absorption spectrophotometer. AB - A simple, uncontaminated method was described for graphite furnace atomic absorption spectrophotometry used for determination of Cd and Pb in milk serum prepared by spontaneous souring. Samples of raw milk were collected from the bulk holding tanks of 107 dairy farms in six counties in Taiwan. Raw milk samples were placed at room temperature (28 degrees C) for 48 h, to allow the pH to decrease below 4.6 and the casein and fat to precipitate. Milk serum was filtered and then directly injected into a graphite tube. The standard addition method was employed, and .1% phosphoric acid was the matrix modifier. During ashing, a 15-s oxygen influx prevented charcoal accumulation on the graphite tube. The mean recoveries of Cd and Pb from three added concentrations were 93.7% and 94.5%, respectively. The analyzed Cd and Pb concentrations in milk powder using this method were close to the certified values. The mean Cd and Pb contents obtained from 107 samples were .044 ng/ml, ranging from .021 to .173, and 2.03 ng/ml, ranging from .98 to 4.45, respectively. There were no significant differences among the six counties. PMID- 8201051 TI - Enterotoxin-binding glycoproteins in a proteose-peptone fraction of heated bovine milk. AB - The binding of Escherichia coli heat-labile enterotoxin to caseins, whey proteins, milk fat globule membrane, and proteose-peptone fraction from bovine milk was studied by using the Western blot technique. Two toxin-binding glycoproteins, pp16k and pp20k, with molecular weights of 15,500 and 20,000, respectively, were detected only in a proteose-peptone fraction. These glycoproteins were partially purified by ammonium sulfate precipitation and Toyopearl HW 55 gel filtration chromatography. The binding ability to the toxin was destroyed by periodate treatment or beta-galactosidase treatment, indicating that a carbohydrate moiety, particularly a terminal galactosyl residue, was essential for the binding of the toxin. In contrast, the binding ability was not changed by mild acid treatment, and these glycoproteins did not bind cholera toxin, which can bind to ganglioside GM1, suggesting that the carbohydrate structure of the glycoproteins is different from that of GM1. The N-terminal amino acid sequence and immunoblot analysis indicated that the protein moieties of pp16k and pp20k are identical to alpha-lactalbumin and beta-lactoglobulin, respectively. These toxin-binding glycoproteins were not detected in whey proteins isolated from unheated skim milk, suggesting that they are newly generated during heat treatment of skim milk before the preparation of a proteose peptone fraction. PMID- 8201053 TI - Volumetric flow rate comparisons for water and product on pasteurization systems. AB - A flow calibration tube system was assembled to determine the volumetric flow rates for water and various dairy products through a holding tube, using three different flow promotion methods. With the homogenizer, the volumetric flow rates of water and reconstituted skim milk were within 1.5% of each other. With the positive displacement pump, the flow rate for reconstituted skim milk increased compared with that for water as the pressure increased or temperature decreased. The largest increase in flow rate was at 310-kPa gauge and 20 degrees C. On a magnetic flow meter system, the volumetric flow rates of water and reconstituted skim milk were within .5% of the flow rate measured from the volume collected in a calibrated tank. The flow rate of whole milk was similar to that of skim milk on the three flow promoters evaluated. Ice milk mix increased the flow rate of the positive displacement pump, but not the homogenizer and magnetic flow meter system. PMID- 8201054 TI - Coagulase-positive Staphylococcus intramammary infections in primiparous dairy cows. AB - Objectives were to determine the prevalence of coagulase-positive staphylococcal IMI in primiparous cows at first parturition, to contrast the differences in coagulase-positive staphylococcal IMI in primiparous cows at parturition in herds with high and low prevalences of coagulase-positive staphylococcal IMI in the lactating herd, and to determine the percentage of primiparous cows having persistent coagulase-positive staphylococcal IMI. Milk samples were collected aseptically from cows at the start and end of the study, at dry-off, and at parturition. Herds (n = 18) were split evenly into two categories: high (> 10%) or low (< 5%) prevalence of coagulase-positive staphylococcal IMI. At the start, the mean prevalence of coagulase-positive staphylococcal IMI in high prevalence herds was 30%, ranging from 13 to 65%, and in low prevalence herds was 2%, ranging from 0 to 5%. Overall the prevalence of coagulase-positive staphylococcal IMI in primiparous cows at parturition was 8.1% (67 of 828), ranging from 0 to 27%. Although primiparous cows from high prevalence herds had a higher prevalence of coagulase-positive staphylococcal IMI (9.2%; 40 of 436) at parturition than did primiparous cows from low herds (6.9%; 27 of 392), the difference was not significant. Of primiparous cows with coagulase-positive staphylococcal IMI at parturition, 43% had coagulase-positive staphylococcal IMI at least 2 mo after parturition. Primiparous cows with coagulase-positive staphylococcal IMI at parturition may represent significant reservoirs of infection to uninfected herdmates. PMID- 8201055 TI - Adherence of Staphylococcus aureus to cultured bovine mammary epithelial cells. AB - Bovine mammary secretory cells, isolated at necropsy, were cultured in vitro and used as a model to study the mode of adherence of Staphylococcus aureus to mammary epithelium. Cultured cells were characterized by their morphology and physiology as secretory epithelial cells. Cells showed characteristic growth patterns when grown on polystyrene, fibronectin, laminin, collagen, and reconstituted basement membrane from the Engelbreth-Holm-Swarm murine sarcoma. Cells cultured on collagen formed confluent monolayers and were the most suitable for bacterial adherence studies. Cultured cells stained intensely for cytokeratin and for specific milk proteins, i.e., alpha-casein, beta-casein, alpha lactalbumin, beta-lactoglobulin, and lactoferrin. The effect of frozen storage for 10 mo on cell viability or presence of milk proteins was minimal. Staphylococcus aureus showed large affinity for extracellular matrix components, i.e., fibronectin, laminin, and collagen. Adherence to confluent cell monolayers was minimal. In preconfluent cell monolayers, most S. aureus adhered more readily to the exposed matrix than to the epithelial cells. Overnight exposure to staphylococcal alpha-toxin greatly increased adherence of S. aureus to confluent monolayers. However, whether bacteria adhered to alpha-toxin damaged cells or to exposed matrix is not clear. Unencapsulated S. aureus adhered in larger numbers than did encapsulated S. aureus. PMID- 8201056 TI - Reverse pressure gradients across the teat canal related to machine milking. AB - Miniature pressure transducers were inserted through the udder cistern wall of 10 cows and placed into the teat cistern and, in addition, beneath the teat end. Data were sampled every millisecond and collected during 59 sequences of manual teat handling pre- and postmilking, 575 attachments, 384 sequences of 30-s milking, and 623 sequences of detachment. Attachment and detachment were mainly done during overmilking in short sequences lasting 8 to 20 s. Reverse pressure gradients across the teat canal occurred during manual teat handling (54%), attachment of the milking unit (29%), milking (1%), and detachment (26%). Overall risk included empty teats. Risk factors at pre- and postmilking teat handling were the compression of teats and the following movement back to normal shape. When the diameter of the mouthpiece orifice of the liner was larger than the teat diameter, the frequency of reverse pressure gradients at attachment was halved compared with attachment of more narrow liners. The method of attaching the milking unit on empty teats without the risk of creating reverse pressure gradients was not identified. Reverse pressure gradients in empty teats may be avoided during detachment of liners if the mouthpiece orifice diameter is greater than the teat diameter. Detachment with the liner in open position reduced the risk of reverse pressure gradients compared with that from the closed position. PMID- 8201057 TI - "I only read about myself on bathroom walls": the need for research on the mental health of lesbians and gay men. AB - The very recent history of pathologizing homosexuality still has a strong impact on the public in general and mental health professionals in particular. In contrast to the early research on sexual reorientation of lesbians and gay men, there is relatively little empirical research on the mental health issues of lesbians and gay men. Whether researchers choose to define sexual orientation by sexual behavior, self-definition, or membership in lesbian and gay community groups will have an impact on the results. Research on mental health issues that include lesbians, gay men, and heterosexual women and men would allow an examination of the relative salience of gender versus sexual orientation. Finally, the experiences of lesbians and gay men in society may place them at increased risk for some mental health problems and may protect them from other mental health problems. PMID- 8201058 TI - The practice and ethics of sexual orientation conversion therapy. AB - Sexual orientation conversion therapy was the treatment of choice when homosexuality was thought to be an illness. Despite the declassification of homosexuality as a mental illness, efforts to sexually reorient lesbians and gay men continue. The construct of sexual orientation is examined, as well as what constitutes its change. The literature in psychotherapeutic and religious conversion therapies is reviewed, showing no evidence indicating that such treatments are effective in their intended purpose. A need for empirical data on the potentially harmful effects of such treatments is established. Ethical considerations relative to the ongoing stigmatizing effects of conversion therapies are presented. The need to develop more complex models for conceptualizing sexual orientation is discussed, as well as the need to provide treatments to gay men and lesbians that are consonant with psychology's stance on homosexuality. PMID- 8201059 TI - National Lesbian Health Care Survey: implications for mental health care. AB - This article presents demographic, lifestyle, and mental health information about 1,925 lesbians from all 50 states who participated as respondents in the National Lesbian Health Care Survey (1984-1985), the most comprehensive study on U.S. lesbians to date. Over half the sample had had thoughts about suicide at some time, and 18% had attempted suicide. Thirty-seven percent had been physically abused as a child or adult, 32% had been raped or sexually attacked, and 19% had been involved in incestuous relationships while growing up. Almost one third used tobacco on a daily basis, and about 30% drank alcohol more than once a week, 6% daily. About three fourths had received counseling at some time, and half had done so for reasons of sadness and depression. Lesbians in the survey also were socially connected and had a variety of social supports, mostly within the lesbian community. However, few had come out to all family members and coworkers. Level of openness about lesbianism was associated with less fear of exposure and with more choices about mental health counseling. PMID- 8201060 TI - Ethnic-minority lesbians and gay men: mental health and treatment issues. AB - Clinical psychological research has been a part of a significant growth of scholarly literature in mental health that appropriately explores relevant cultural variables and their effects on both the mental health and treatment of ethnic minority group members. A similar expansion of material seeking to develop affirmative perspectives in the treatment of gay men and lesbians has also found its way into the psychological literature. Scarcely any research seeks to explore the particular psychological strengths and vulnerabilities of men and women who are members of both groups. This article reviews literature pertinent to the cultural proscriptions of several ethnic minority groups and their relevance to mental health issues and treatment of gay and lesbian members, as well as a review of potential countertransference dilemmas for therapists. PMID- 8201061 TI - Sexual orientation and gender as factors in socioculturally acquired vulnerability to body dissatisfaction and eating disorders. AB - This study investigated the hypothesis that gay men and heterosexual women are dissatisfied with their bodies and vulnerable to eating disorders because of a shared emphasis on physical attractiveness and thinness that is based on a desire to attract and please men. Although men place priority on physical attractiveness in evaluating potential partners, women place greater emphasis on other factors, such as personality, status, power, and income. Therefore, lesbians and heterosexual men are less concerned with their own physical attractiveness and, consequently, less dissatisfied with their bodies and less vulnerable to eating disorders. Several instruments measuring body satisfaction, the importance of physical attractiveness, and symptoms of eating disorders were administered to 250 college students. The sample included 53 lesbians, 59 gay men, 62 heterosexual women, and 63 heterosexual men. Multivariate and univariate analyses of variance were used to examine the differences among the scores of lesbians, gay men, heterosexual women, and heterosexual men on these various constructs. The results generally confirmed the research hypothesis. The implications and ramifications these findings have for the understanding of both the psychology of lesbians and gay men and the prevention and treatment of eating disorders are discussed. PMID- 8201062 TI - Verbal and physical abuse as stressors in the lives of lesbian, gay male, and bisexual youths: associations with school problems, running away, substance abuse, prostitution, and suicide. AB - A common theme identified in empirical studies and clinical reports of lesbian, gay male, and bisexual youths is the chronic stress that is created by the verbal and physical abuse they receive from peers and adults. This article reviews the verbal and physical abuse that threatens the well-being and physical survival of lesbian, gay male, and bisexual youths. This response to gay male, lesbian, and bisexual adolescents by significant others in their environment is often associated with several problematic outcomes, including school-related problems, running away from home, conflict with the law, substance abuse, prostitution, and suicide. Although the causal link between these stressors and outcomes has not been scientifically established, there is suggestive evidence that these outcomes are consequences of verbal and physical harassment. PMID- 8201063 TI - Impact of psychological and physical health, stressful events, and social support on subsequent mental health help seeking among older adults. AB - Factors that influence mental health help seeking among adults 55+ years were examined prospectively. A discriminant analysis significantly differentiated between 120 older adults needing and seeking services and a comparison group of 120 older adults not needing services. Prior to having sought help, help seekers demonstrated poorer psychological well-being, reported more physical health problems, reported a higher level of unpleasant stressful events, and perceived greater deficits in the amount of social support available to them in time of need. The vast majority of these older help seekers sought help for their mental health problems from a medical doctor rather than from a mental health center or clinic or from a minister. Significantly more help seekers than nonseekers experienced stressful events involving bereavement, social and economic loss, and new physical illness. PMID- 8201064 TI - Blind man's bluff: effectiveness and significance of psychotherapy and pharmacotherapy blinding procedures in a clinical trial. AB - No study has reported on the comparative effectiveness of blinding procedures for psychotherapy and pharmacotherapy conditions in treatment efficacy studies or the potential impact of failure to maintain a psychotherapy blind. In a randomized clinical trial, we found, from the perspective of clinical evaluators who were unaware of the patient's treatment assignment, procedures intended to protect the psychotherapy blind were only modestly effective but comparable to standard procedures used to maintain pharmacotherapy blinds. Second, accuracy of guessing each form of treatment (psychotherapy or pharmacotherapy) was not independent of the other. Third, findings suggested the importance of maintaining both psychotherapy and pharmacotherapy blinds, as subjective ratings of treatment outcome were significantly different depending on whether the clinical evaluator had correctly guessed the patients' true treatment condition. PMID- 8201065 TI - Statistical analysis of ordinal categorical status after therapies. AB - Appropriate statistical analysis of clinical data based on ordinal categorical outcome scales is discussed. Chi-square analysis is inappropriate for testing the superiority of one therapy over another when outcome is ordinal categorical. Emphasized is estimation of clinically informative effect sizes after statistical significance has been attained with the Mann-Whitney U test. Little-used informative measures of effect size are related to estimation of the probability that a client given one therapy will have an outcome superior to that of a client given another therapy. PMID- 8201066 TI - Application of random-effects probit regression models. AB - A random-effects probit model is developed for the case in which the outcome of interest is a series of correlated binary responses. These responses can be obtained as the product of a longitudinal response process where an individual is repeatedly classified on a binary outcome variable (e.g., sick or well on occasion t), or in "multilevel" or "clustered" problems in which individuals within groups (e.g., firms, classes, families, or clinics) are considered to share characteristics that produce similar responses. Both examples produce potentially correlated binary responses and modeling these person- or cluster specific effects is required. The general model permits analysis at both the level of the individual and cluster and at the level at which experimental manipulations are applied (e.g., treatment group). The model provides maximum likelihood estimates for time-varying and time-invariant covariates in the longitudinal case and covariates which vary at the level of the individual and at the cluster level for multilevel problems. A similar number of individuals within clusters or number of measurement occasions within individuals is not required. Empirical Bayesian estimates of person-specific trends or cluster-specific effects are provided. Models are illustrated with data from mental health research. PMID- 8201067 TI - Psychosocial risk factors for future adolescent suicide attempts. AB - An array of psychosocial risk factors for making a suicide attempt were examined in a representative sample of 1,508 older (14- to 18-year-old) high school students, 26 of whom made a suicide attempt during the year following entry into the study. Strongest predictors of future suicide attempt were history of past attempt, current suicidal ideation and depression, recent attempt by a friend, low self-esteem, and having been born to a teenage mother. The results suggest that adolescents who are depressed and those who attempt suicide share many psychosocial risk factors. The efficacy of two screeners (one consisting of 4 items and the other of 6 variables) is reported. Potential usefulness for research and communitywide prevention is discussed. PMID- 8201068 TI - The treatment of recurrent abdominal pain in children: a controlled comparison of cognitive-behavioral family intervention and standard pediatric care. AB - This study describes the results of a controlled clinical trial involving 44 7- to 14-year-old children with recurrent abdominal pain who were randomly allocated to either cognitive-behavioral family intervention (CBFI) or standard pediatric care (SPC). Both treatment conditions resulted in significant improvements on measures of pain intensity and pain behavior. However, the children receiving CBFI had a higher rate of complete elimination of pain, lower levels of relapse at 6- and 12-month follow-up, and lower levels of interference with their activities as a result of pain and parents reported a higher level of satisfaction with the treatment than children receiving SPC. After controlling for pretreatment levels of pain, children's active self-coping and mothers' caregiving strategies were significant independent predictors of pain behavior at posttreatment. PMID- 8201069 TI - A therapeutic index: measuring therapeutic actions in psychotherapy. AB - This article describes a research method that measures a therapist's effectiveness by assigning a composite value to each therapeutic verbal statement during a session. The intrasubject averaging of these values is called the mean therapeutic index (sigma). In this study, whether the mean therapeutic index could be used to predict treatment outcome was investigated. A successful case and an unsuccessful case were selected for 15 therapists, and an early session for each case was coded using the mean therapeutic index. The results show that the magnitude of the effect of the mean therapeutic index, as indicated by the correlation coefficient r, was .92 (r2 = 0.85). Thus, the mean therapeutic index accounted for 85% of the variance in the classification of treatment outcome as successful or unsuccessful. The findings point to the method's potential use for clinical practice and supervision of psychotherapy. PMID- 8201070 TI - Primary and secondary control among children undergoing medical procedures: adjustment as a function of coping style. AB - The literature suggests that optimal adjustment to relatively uncontrollable stressors may require adjusting oneself to the stressors rather than trying to alter them. This possibility was explored, for low-controllability stressors (e.g., painful medical procedures) associated with leukemia. Children's reports of coping strategies and goals were classified as primary control coping (attempts to alter objective conditions), secondary control coping (attempts to adjust oneself to objective conditions), or relinquished control (no attempt to cope). Secondary control coping was positively associated with (a) general behavioral adjustment assessed by the Child Behavior Checklist and (b) illness specific adjustment assessed by children's own distress ratings and by behavioral observations during painful procedures. All significant group differences showed better adjustment among secondary control children than among the primary or relinquished groups. PMID- 8201071 TI - Somatic symptoms, social support, and treatment seeking among sexual assault victims. AB - In an effort to clarify the relationship between the experience of sexual assault and physical health, rape victims and a matched comparison group were repeatedly assessed for somatic symptoms, psychological distress, health care use, and self rated health perceptions during the year immediately after the assault. Women who experienced sexual assault reported more somatic complaints, poorer perceptions of physical health, greater psychological distress, and increased use of medical services. However, victims did not show a significantly higher use of mental health services and continued to seek medical attention at the end of the year after the assault, when health perceptions and somatic symptoms were no longer significantly elevated. The use of mental health services and social support as moderating variables are examined, and implications for the medical and psychological treatment of sexual assault victims are discussed. PMID- 8201072 TI - Acute and chronic low back pain: cognitive, affective, and behavioral dimensions. AB - Despite strong suppositions concerning differences between patients suffering acute and chronic low back pain, relatively few data-based comparisons have been made. In this study, affective, cognitive, behavioral, and demographic contrasts were conducted. Chronic patients were divided into those who demonstrated signs and symptoms that were either congruent or incongruent with underlying anatomical and physiological principles. Low socioeconomic status, compensation claims, use of opiate analgesics, greater disability, catastrophizing cognitions, stronger emotionality, and passive coping were more characteristic of both acute and chronic incongruent patients than chronic congruent patients. A relatively stereotyped, spontaneous facial expression of pain was observed in all groups when responding to painful movements during a physical examination. The similarities between acute and chronic incongruent patients have implications for the assessment and treatment of low back pain. PMID- 8201073 TI - Social phobia: a comparison of behavior therapy and atenolol. AB - Seventy-two social phobics were randomly assigned to behavioral (flooding) or drug treatment with atenolol or placebo. Treatment was administered over a 3 month period of time, and duration of treatment effects was determined at a 6 month follow-up assessment. Multiple measures of outcome were used, including self-report, clinician ratings (including assessment by independent evaluators), behavioral assessment, and performance on composite indexes. The results indicated that flooding consistently was superior to placebo, whereas atenolol was not. Flooding also was superior to atenolol on behavioral measures and composite indexes. Those subjects who improved during treatment maintained gains at the 6-month follow-up regardless of whether they received flooding or atenolol. The variability of outcome on different measures in social phobia research is discussed, and the need for broad-based treatment strategies to address the pervasive deficits associated with social phobia is noted. PMID- 8201074 TI - Predicting prospective episodes of depression in patients with panic disorder: a longitudinal study. AB - This study used a naturalistic, longitudinal study to examine predictors of the emergence of major depression among 90 nondepressed patients with panic disorder who were followed for a 2-year period. Twenty-four percent of the sample experienced a major depressive episode during the study period. Adequacy and type of medication treatment were not associated with decreased risk. Past history of major depression was associated with a greater risk for a prospective episode. The degree of assertiveness, presence of comorbid generalized anxiety disorder, and severity of agoraphobia were each significant predictors of the occurrence of depression when considered alone and when the influence of past history of depression was statistically controlled. The implications of these findings for the clinical management of patients with panic disorder are discussed. PMID- 8201075 TI - Social-cognitive processes of severely violent, moderately aggressive, and nonaggressive boys. AB - This study examined social-cognitive processes of aggressive and nonaggressive boys at preadolescent and early adolescent age levels. The social-cognitive variables included processing of cues, attributions, social problem solving, affect labeling, outcome expectations, and perceived competence and self-worth. Results indicated that a wide range of social-cognitive processes is distorted and deficient for violent and moderately aggressive children, and that different types of social cognition contribute unique variance in discriminating among groups. Severely violent boys at both age levels had difficulties with cue recall, attributions, social problem solving, general self-worth, and a pattern of endorsing unusually positive affects that they may experience in different settings. Moderately aggressive boys shared some of the social-cognitive difficulties demonstrated by severely violent boys, but they also displayed indications that their aggression may be more planfully aimed to achieve expected outcomes. When the moderately aggressive and the violent boys differed from the nonaggressive boys on attributional biases and low perceived self-worth, a continuum existed with violent boys displaying more extreme social-cognitive dysfunctions than the moderately aggressive boys. These findings carry implications for cognitive-behavioral intervention with severely violent and moderately aggressive youths. PMID- 8201076 TI - The relationship between men's sexual aggression inside and outside the laboratory. AB - The purpose of this study was to develop a laboratory analogue of sexually aggressive behavior. Subjects viewed neutral, sexual-violent, and violent-sexual film vignettes and chose a vignette to show to a female confederate. Among highly sexually aggressive men (n = 25) according to the Coercive Sexuality Scale (CSS; Rapaport & Burkhart, 1984), 24% showed the sexual-violent vignette and 28% showed the violent-sexual vignette. Among men who did not report being sexually aggressive on the CSS (n = 13), none showed the sexual-violent vignette and only one showed the violent-sexual vignette. The between-group difference in vignette showing was statistically significant (p < .024). Subjects who showed the sexually aggressive vignettes reported that the female confederate was upset (p < .0001) and uncomfortable (p < .0001) in viewing these vignettes more than the subjects did who showed the neutral vignette. These results support the validity of this film-showing procedure as a laboratory analogue of sexually aggressive behavior. PMID- 8201077 TI - Binge eating disorder: reliability and validity of a new diagnostic category. AB - This study examined the reliability and validity of binge eating disorder (BED), which has been proposed for inclusion in the Diagnostic and Statistical Manual of Mental Disorders ([DSM] 4th ed.; American Psychiatric Association, in press). The interrater reliability of the BED diagnosis compared favorably with that of most diagnoses in the revised third edition of the DSM. To assess validity, we compared obese individuals with and without BED and bulimia nervosa patients. BED subjects differed from the non-BED obese group on variables related to dieting and weight histories but did not differ significantly on other important variables, including measures of psychopathology. When compared with bulimia nervosa patients, subjects with BED had significantly less psychopathology and reported significantly less dietary restraint. This study lends some support to the concept of BED but suggests that additional studies of the characteristics of this disorder at different degrees of obesity would be useful. PMID- 8201078 TI - Psychopathy as a taxon: evidence that psychopaths are a discrete class. AB - Taxometric analyses were applied to the construct of psychopathy (as measured by the Psychopathy Checklist) and to several variables reflecting antisocial childhood, adult criminality, and criminal recidivism. Subjects were 653 serious offenders assessed or treated in a maximum-security institution. Results supported the existence of a taxon underlying psychopathy. Childhood problem behaviors provided convergent evidence for the existence of the taxon. Adult criminal history variables were continuously distributed and were insufficient in themselves to detect the taxon. PMID- 8201079 TI - Infertility and parenthood: does becoming a parent increase well-being? AB - There is a large literature that demonstrates that infertility has a variety of negative effects on women's and men's well-being, but little is known about the impact of becoming a parent. The effects of parenthood were examined in a longitudinal study with both wives and husbands from 174 infertile couples and a comparison group of 74 presumed fertile couples. Infertile women who became parents experienced greater global well-being but diminished marital well-being, compared with infertile women who had not become parents. Infertile men who became parents experienced the same negative effects that their wives reported, but they did not experience positive effects to the same extent. Parental status had fewer positive and negative effects on members of presumed-fertile couples. These results are discussed in terms of gender differences in the meaning of parenthood, and their implications for research and clinical services are considered. PMID- 8201080 TI - Cognition in test-anxious children: the role of on-task and coping cognition reconsidered. AB - This study investigated cognition in children with high, moderate, and low test anxiety under naturalistic test-taking conditions. Children with high test anxiety not only reported more negative self-evaluations and more off-task thoughts but also more on-task and coping thoughts. Consistent with previous research, no "task-facilitating" role for these on-task and coping cognitions was found. This finding lends support to the notion of "the power of non-negative thinking". The only facilitating role was for positive self-evaluations. It was hypothesized that positive cognition could be task-facilitating under certain conditions. Limited support was found for this idea. PMID- 8201081 TI - Criterion validity of informants in the diagnosis of disruptive behavior disorders in children: a preliminary study. AB - The relative validity of the reports of parents, teachers, and children, and combinations of these informants was assessed using measures of concurrent impairment associated with disruptive behavior disorders as criterion variables in a clinic-referred sample of 177 boys ages 7-12 years. For oppositional defiant disorder (ODD) and conduct disorder (CD), the reports from teachers, alone and in combination with parents and children, showed the strongest relations to impairment criteria. The reports of parents and children, alone and in combination, were relatively less valid. For attention-deficit hyperactivity disorder, there were no significant correlations between the reports of any single informant or combination of informants and the impairment criteria. This study provides preliminary support for the validity of multi-informant diagnostic assessment of ODD and CD in children, especially when the teacher is one of the informants. PMID- 8201082 TI - The clinical meaning of the surface roughness and the surface free energy of intra-oral hard substrata on the microbiology of the supra- and subgingival plaque: results of in vitro and in vivo experiments. AB - In the oral cavity, which may be considered as an open growth system, most bacteria can only survive if they adhere to the hard surfaces (teeth, filling materials, dental implants, or prostheses). Such bacterial adhesion occurs in four phases: transport to the surface, initial adhesion with a reversible and irreversible stage, attachment by specific interactions and finally colonization. During this process the roughness and the free energy of the surfaces play a key role. The reduction in roughness of a surface will result in a dramatic retardation of plaque formation and maturation. A reduction in surface free energy of the substratum will result in a decrease in plaque growth rate, a decrease in plaque retention capacity of the surface and in the selection of specific organisms. Although both parameters interact with each other, the influence of surface roughness is dominant. The importance of both parameters justifies the demand for smooth surfaces with a low surface free energy in order to prevent plaque formation, thereby reducing the occurrence of gingival inflammation. PMID- 8201083 TI - Fluoride release from alternative restorative materials. AB - Numerous laboratory studies have been performed to evaluate the fluoride releasing capacity of different restorative materials. The studies have comprised release of fluoride, uptake of fluoride in the dental hard tissues and the inhibitory effect on demineralization. The present paper discusses the results from and the clinical relevance of the laboratory studies especially as regards the glass ionomer materials and resin composites. PMID- 8201084 TI - Occlusal wear simulation with the ACTA wear machine. AB - This paper describes how the clinical conditions in stress bearing areas are thought to be simulated in the ACTA wear machine. The wear types simulated are erosive wear and contact sliding wear in the presence of a third-body medium, consisting of natural food substances. Wear due to surface fatigue may also be studied with the wear machine. Wear rates for a wide range of resin composites, an amalgam and a glass polyalkenoate (ionomer) cement obtained with the ACTA wear machine correlated with an average correlation coefficient of 0.90 with data collected from clinical trials. The results justify the experimental set-up as being one that includes a realistic simulation of the complexity of clinical wear. PMID- 8201085 TI - Bonding of luting materials for resin-bonded bridges: clinical relevance of in vitro tests. AB - A retrospective clinical study on 78 resin-bonded bridges placed between 1981 and 1992 was used to validate the wedge test in the assessment of the bonding of resin-based luting material. According to the correlation obtained between the findings of the in vivo and the in vitro studies, the wedge test may be considered to be predictive of the clinical performance of resin bonds. The life expectancy of resin-bonded bridges bonded with the 4 META containing material tested appears to be longer than that for bridges bonded with conventional resin cements. PMID- 8201086 TI - Clinical relevance of laboratory studies on dental materials: strength determination--a personal view. AB - The measurement of strength of materials is undertaken in a laboratory primarily to determine its relationship to the microstructural features of the material, as the understanding it brings will allow the production of stronger materials. Problems arise when attempts are made to derive some sort of clinical significance from these data without due regard to the functional aspects of the device from which the material is made. Three examples are presented which seek to highlight that: (1) strength, however desirable, is not necessarily the most important consideration; (2) great care has to be exercised in interpreting strength data; and (3) the most appropriate properties are considered for each individual dental application of the material. PMID- 8201087 TI - Marginal integrity: clinical significance. AB - The marginal integrity of restorations is an important parameter as marginal gap formation is associated with recurrent caries and pulpal disease. Testing of marginal integrity in vitro is viewed with uncertainty due to interactions and interpretation problems. The clinical evaluation of marginal behaviour is also questionable due to the lack of reliable diagnostic skills of the clinician. The scientific community must recognize that in vitro and in vivo testing have severe limitations and accept that materials will be misjudged during evaluation processes. PMID- 8201088 TI - Low intramucosal pH is associated with failure to acidify the gastric lumen in response to pentagastrin. AB - OBJECTIVE: To determine if low gastric intramucosal pH is associated with impaired secretion of gastric acid after pentagastrin stimulation. DESIGN: Prospective study. SETTING: Intensive care unit of a university teaching hospital. PATIENTS: 20 patients requiring mechanical ventilation. INTERVENTIONS: All patients with a gastric luminal pH > 4 were given pentagastrin 6 micrograms/kg s.c. to stimulate gastric acid secretion and the response assessed by further measurements of gastric luminal pH. MEASUREMENTS AND RESULTS: Gastric intramucosal pH (pHi) and luminal pH (pHL) were measured. Patients were divided into two groups on the basis of a low or normal pHi (A value of 7.35 was taken as the lower limit of normal). Patients (n = 6) with normal pHi (7.40 +/- 0.05 [mean +/- SD]) and a luminal pH > 4 (5.65 +/- 1.25) all had a decrease in pHL in response to pentagastrin (decrease in pHL 4.02 +/- 1.52). Of the patients (n = 7) with low pHi (7.2 +/- 0.13) and a pHL > 4 (6.51 +/- 0.48) only one responded to pentagastrin (decrease in pHL for this group 0.93 +/- 1.86). Patients with a pHL < 4 (2.4 +/- 0.71) were not given pentagastrin (n = 7). CONCLUSION: Some critically ill patients with low gastric intramucosal pH appear to have an impaired ability to acidify the gastric lumen in response to pentagastrin. PMID- 8201089 TI - Rapid fall in blood myoglobin in massive rhabdomyolysis and acute renal failure. AB - OBJECTIVE: Myoglobin kinetics of removal from the circulation were studied in patients following massive rhabdomyolysis, to see if myoglobin remains for long in the circulation in the anuric state and if myoglobin elimination was affected by therapeutic manipulation such as haemofiltration or haemodialysis. DESIGN: Randomised and controlled study. SETTING: Intensive care unit of a tertiary care teaching hospital. PATIENTS: 26 patients of rhabdomyolysis whose serum myoglobin exceeded more than 500 nmol/l. Thirteen patients developed acute renal failure and underwent treatment with blood purification (Group HD). The remaining 13 patients did not require treatment with blood purification (control subjects, Group non-HD). INTERVENTIONS: In patients of group HD, twelve were treated with haemofiltration and/or haemodialysis. One was treated with peritoneal dialysis. The patient of group non-HD were treated with fluid infusion alone. MEASUREMENTS AND RESULTS: The serum concentrations of myoglobin were serially determined. The highest levels of myoglobin was 1641 +/- 484 nmol/l (mean +/- SEM) in the group non-HD and were 8957 +/- 2300 in the group HD. In the group non-HD, the blood myoglobin fell exponentially once myoglobin release into the circulation ceased. This was also noted in the group HD. The exponential decrease was observed even on the days when the patient passed little urine or treatment with blood purification was not performed. CONCLUSION: In patients with massive myoglobinaemia, the blood myoglobin rapidly fell independent of renal function or any therapeutic manipulation. The results indicate that extrarenal factors played a major role in disposing circulating myoglobin in such patients. PMID- 8201090 TI - Glucose and urea production and leucine, ketoisocaproate and alanine fluxes at supraphysiological plasma adrenaline concentrations in volunteers. AB - OBJECTIVE: To determine the magnitude and time course of adrenergic effects on metabolism in volunteers and possible implications for the use of sympathomimetics in the critically ill. DESIGN: Descriptive laboratory investigation. SUBJECTS: 7 volunteers. INTERVENTION: Primed continuous infusions of stable isotope tracers ([15N2]-urea, [6,6-D2]-glucose, [methyl-D3]-L-leucine, [15N]-L-alanine) were used. After isotopic steady state had been reached an infusion of adrenaline (0.1 microgram/kg/min) was administered (4 h). Isotopic enrichment was measured using gas chromatography-mass spectrometry and the corresponding rates of appearance were calculated. MEASUREMENTS AND MAIN RESULTS: Glucose production increased from 14.1 +/- 1.2 to 21.5 +/- 2.0 mumol/kg/min (p < 0.05) after 80 min of adrenergic stimulation and then decreased again to 17.9 +/- 1.2 mumol/kg/min after 240 min. Leucine and ketoisocaproate (KIC) fluxes were 2.3 +/- 0.2 and 2.6 +/- 0.2 mumol/kg/min, respectively, at baseline and gradually decreased to 1.8 +/- 0.2 and 2.2 +/- 0.1 mumol/kg/min, respectively, after 240 min of adrenaline infusion (both p < 0.05). Alanine flux increased from 3.7 +/- 0.5 to 6.9 +/- 0.9 mumol/kg/min (p < 0.05) after 80 min of adrenergic stimulation. Urea production slightly decreased from 4.8 +/- 0.9 to 4.3 +/- 0.8 mumol/kg/min during adrenaline (p < 0.05). CONCLUSIONS: Adrenaline induced an increase in glucose production lasting for longer than 240 min. The decrease in leucine and KIC flux suggests a reduction in proteolysis, which was supported by the decrease in urea production. The increase in alanine flux is therefore most likely due to an increase in de-novo synthesis. The ammonia donor for alanine synthesis in peripheral tissues and the target for ammonia after alanine deamination in the liver remain to be investigated. These results indicate that adrenaline infusion most probably will not promote already enhanced proteolysis in critically ill patients. Gluconeogenesis is an energy consuming process and an increase may deteriorate hepatic oxygen balance in patients. PMID- 8201091 TI - Cardiotoxicity of colchicine in the rat. AB - OBJECTIVES: Colchicine poisoning may be lethal and a decrease in cardiac function has been reported in several case reports, but the precise cardiotoxicity of colchicine remains unknown. DESIGN: The experimental in vitro study assessed the intrinsic contractility of left ventricular papillary muscle in rats, 24 h after administration of intraperitoneal colchicine or saline. RESULTS: The administration of colchicine (2 or 4 mg.kg-1) in adult Wistar rats markedly impaired intrinsic myocardial contractility, as shown by a decrease in maximum shortening velocity (-32 and -61%, respectively), active isometric force (-47 and -65%, respectively), and peak power output (-57 and -69%, respectively) of left ventricular papillary muscle. Colchicine impaired isotonic relaxation and load dependence of relaxation, suggesting a decrease in sarcoplasmic reticulum function. Conversely, colchicine significantly accelerated isometric relaxation, suggesting a decrease in calcium myofilament sensitivity. Myothermal economy was markedly impaired only in some rats (3/10 in each group), in which the negative inotropic effect of colchicine appeared to be more particularly pronounced. CONCLUSION: The results indicate that the administration of high doses of colchicine induced intrinsic cardiotoxic effects. Due to its amplitude, such cardiotoxic action may participate in the fatal outcome of acute colchicine poisoning. PMID- 8201092 TI - Functional deterioration of the liver by elevated inferior vena cava pressure: a proposed upper safety limit of pressure for maintaining liver viability in dogs. AB - OBJECTIVE: Abnormally elevated central venous pressure is considered to be an etiological factor in the onset of acute hepatic failure following modified Fontan operation. This paper hypothesises that an increase in inferior vena cava pressure (IVCP) after such an operation has adverse effects on hepatic energy status. DESIGN: Various degrees of venous hypertension were produced in 10 mongrel dogs by clamping the thoracic IVC with an active veno-venous shunt and varying its flow rate from 60-2.5 ml/min/kg. Arterial ketone body ratio (KBR), reflecting the hepatic mitochondrial redox state, was measured as an index of hepatic energy status. MEASUREMENTS AND RESULTS: The lower the flow rates of the shunt, the higher the pressures of IVC and portal vein, while systolic blood pressure was maintained above 100 mmHg. CO significantly decreased when the pump speed was less than 30 ml/min/kg. KBR showed a negative correlation to IVCP as well as a positive correlation to portal blood flow (p < 0.05). CONCLUSION: From the simple regression line obtained between IVCP and KBR, it was determined that an upper safety limit of IVCP may lie at about 27 cmH2O (20.5 mmHg), and that a IVCP of 35 cmH2O (26.6 mmHg) seems to be the critical level for maintaining liver viability. PMID- 8201093 TI - Effects of dobutamine on oxygen transport and consumption in the adult respiratory distress syndrome. AB - OBJECTIVE: To determine if oxygen consumption (VO2) in patients with adult respiratory distress syndrome (ARDS) is dependent on, and thus limited by, oxygen transport (TO2) rather than O2 demand. DESIGN: Prospective study. SETTING: Intensive care unit of a tertiary referral center. PATIENTS: 12 patients with ARDS and sepsis syndrome. INTERVENTIONS: Routine intensive care unit monitoring including pulmonary and radial artery catheters. MEASUREMENTS: Dobutamine was used to increase cardiac output, thereby directly varying TO2 under conditions of constant O2 demand. After baseline measurements of TO2 and VO2, dobutamine was infused intravenously at progressively increasing doses of 5, 10, 15 and 20 micrograms/kg/min and measurements of TO2 and VO2 were repeated after 30 min at each dose. RESULTS: Dobutamine increased TO2 in 8 of the 12 patients, by 29% at 5 micrograms/kg/min and by 45% (net) at 10 micrograms/kg/min, but not at higher doses. In these 8 patients dobutamine also increased VO2 by 15% at 5 micrograms/kg/min, but did not further increase VO2 at higher doses. There was no correlation between baseline blood lactate concentration and the response of either TO2 or VO2 to dobutamine. CONCLUSIONS: In some but not all patients with ARDS and sepsis syndrome, short-term infusion of low-dose dobutamine can increase both TO2 and VO2. Achievement of a TO2-independent level of VO2 could not be convincingly demonstrated in any individual patient. The response of TO2 and VO2 to dobutamine could not be predicted from baseline blood lactate concentration. Determination of the impact on patient outcome of a more prolonged infusion of dobutamine requires further study. PMID- 8201094 TI - Hemodynamic changes in acute adrenal insufficiency. AB - OBJECTIVE: Acute adrenocortical insufficiency is an unusual cause of isolated shock. The purpose of this study is to describe the cardiovascular changes in 6 patients with acute adrenal insufficiency presenting with hemodynamic instability. DESIGN: Retrospective and prospective study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: 6 patients studied by right cardiac catheterization. MEASUREMENTS AND RESULTS: Results before glucocorticoid treatment show two possible hemodynamic states: 1) myocardial depression with hypovolemia in 3 patients, and 2) hyperdynamic shock with high cardiac output and diminished systemic arterial resistance in 3 other patients. The 3 patients presenting hyperdynamic shock were all given intravenous fluid therapy of over 20 ml/kg before the first hemodynamic measurement. For 2 other patients with low cardiac index and high systemic arterial resistance studied prospectively, 20 ml/kg intravenous fluid therapy transformed the hemodynamic state to hyperdynamic shock. The cardiovascular effect of glucocorticoid treatment studied in 4 patients was resulted in an improvement in the left ventricular systolic work index. CONCLUSIONS: Diagnosis of acute adrenocortical insufficiency must be considered if clinical manifestations are present suggesting septic shock without any obvious infectious cause in patients having undergone considerable intravenous fluid therapy as an initial course of treatment. PMID- 8201095 TI - Swan-Ganz catheter-related pulmonary valve infective endocarditis: a case report. AB - We report the case of a 29-year-old man with decompensated alcoholic cardiomyopathy who developed a Staphylococcal pulmonic valve infective endocarditis during hemodynamic monitoring, as a consequence of catheter-related bacteremia. As experimentally demonstrated, the damaging role of the pulmonary artery catheter on the endocardial surface plays a major role in the pathogenesis of related right-sided infective endocarditis. Occurrence of bacteremia in a catheterized patient should be considered as a high risk situation, and righ heart infective endocarditis must be suspected whenever patient presents fever or bacteremia without obvious site of infection. Doppler echocardiography is the reference diagnosis procedure. PMID- 8201096 TI - Death by tanning--a case of fatal basic chromium sulphate poisoning. AB - A woman ingested 400 ml of leather tanning solution containing 48 g of basic chromium sulphate (CrOHSO4). This substance forms hydrogen ions and trivalent chromium when it reacts with tissue proteins. The patient died of cardiogenic shock, complicated by pancreatitis and gut mucosal necrosis and haemorrhage. There are no reported cases of toxicity due to oral ingestion of trivalent chromium. Toxicity of hexavalent and trivalent chromium is discussed and suggestions made for management of future cases. PMID- 8201098 TI - Guidelines for the utilisation of intensive care units. European Society of Intensive Care Medicine. PMID- 8201099 TI - Drug treatment during continuous haemofiltration. PMID- 8201097 TI - Consensus conference on mechanical ventilation--January 28-30, 1993 at Northbrook, Illinois, USA. Part 2. PMID- 8201100 TI - Pulmonary air embolism. PMID- 8201101 TI - Continuous intra-arterial blood gas monitoring. PMID- 8201102 TI - Uncertainty in the management of ARDS: lessons for the evaluation of a new therapy. PMID- 8201103 TI - Intramucosal pH. PMID- 8201104 TI - Bacteremia, sepsis and shock. PMID- 8201105 TI - Nosocomial bacteremia in a medical-surgical intensive care unit: epidemiologic characteristics and factors influencing mortality in 111 episodes. AB - OBJECTIVE: To analyze the epidemiology and factors influencing mortality of ICU acquired bacteremia. DESIGN: Prospective clinical study. SETTING: A medical surgical ICU in an university hospital. PATIENTS: We recorded variables from 111 consecutive ICU-acquired episodes for a 3-year period. RESULTS: The attack rate was 1.9 episodes per 100 patient-days. The commonest isolates were coagulase negative staphylococci, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Intravascular catheters were the most frequent source of infection. Overall mortality was 31.5%, and 65.7% of all deaths were directly attributable to infection. Bacteremia from intra-abdominal, lower respiratory tract or unknown origin were associated with a poor prognosis. A logistic regression analysis defined intraabdominal origin (p = 0.01, OR = 15.7) and presence of shock (p = 0.04, OR = 3.3) as independently influencing the risk of death. No significant differences were found for the remaining variables studied. CONCLUSIONS: Epidemiology and etiology of ICU-acquired bacteremia does not differ seriously in respect to nosocomial bacteremia among unselected populations, although it is associated with a greater incidence and overall mortality. Presence of shock is the most important modificable variable affecting the outcome. PMID- 8201106 TI - Intra-operative gut mucosal hypoperfusion is associated with increased post operative complications and cost. AB - OBJECTIVES: To determine CO and gastric mucosal perfusion in patients during elective major surgery; to seek a relationship with subsequent outcome. DESIGN: Prospective descriptive study. SETTING: University hospital. PATIENTS: 51 patients undergoing elective major surgery of an anticipated duration of greater than 2 h who were at risk of developing gut mucosal hypoperfusion and postoperative organ failure. MEASUREMENTS AND RESULTS: CO was determined by oesophageal Doppler measurement of aortic blood flow. Gastric mucosal perfusion was determined by tonometric assessment of gastric mucosal pH (pHi). Blood pressure and urine flow were measured. At the end of surgery no patients were oliguric or hypotensive. Post-operatively morbidity, mortality, duration and cost of stay in the ITU and hospital were assessed. There were 32 patients with evidence of gastric mucosal ischaemia at the end of surgery (pHi < 7.32) despite maintenance of CO. This group of patients spent a mean of 4.7 (range 0-33) days in the ITU, 14 developed major complications (7 with multiple organ failure [MOF] and 6 died. In 19 patients gut mucosal perfusion was maintained during surgery (pHi > or = 7.32); these patients demonstrated an increase in CO of 48.4% (95% confidence interval 21.3 -75.6) and spent a mean of 1.0 (range 0-4) days in the ITU. Only one developed a major complication and none died. The total cost of post-operative care for the 51 patients was estimated at pounds 356650. Mean cost per patient in the low pHi group was significantly greater at pounds 8845 (range pounds 600--pounds 42,700) compared to pounds 3874 (range pounds 2,600--pounds 9,600) in the normal pHi group. The total.cost of post-operative care for the 7 patients who developed MOF was pounds 171,450 i.e. 48% of the total cost. CONCLUSION: A low gastric pHi measured during the intraoperative period in a group of patients undergoing major (mainly cardiovascular) surgery is associated with increased post-operative complications and cost. PMID- 8201107 TI - A dual filter model describing single-fiber responses to clicks in the normal and noise-damaged cochlea. AB - This paper presents a composite model of the normal and noise-damaged guinea pig cochlea. The model incorporates a phenomenologically defined cochlear filter, and physiological descriptions of inner hair cell transduction, synaptic adaptation, and spike generation. The latter three model sections were taken from recent literature. The paper first deals with validation and evaluation of the model and adaptation of the relevant parameters to the guinea pig. Then the model is applied to explore to what extent changes in the cochlear filter can be held responsible for abnormal responses to clicks that were recorded in single auditory nerve fibers in noise-damaged animals. Focus is on those fibers in which the tip-to-tail sensitivity ratio of the frequency threshold curve (FTC) has decreased and/or in which the FTC tail has become hypersensitive. Inspired by this type of W-shaped FTC the mechanical response of the basilar membrane is phenomenologically modeled by two parallel filters, one responsible for the tip of the FTC, the other for its tail. Model simulations show that most abnormal temporal response properties can be explained by pathological alterations in the mechanical response. Residual discrepancies between model and experiment are identified which presumably point to pathological changes in other stages of cochlear processing. PMID- 8201108 TI - The middle ear muscle of frogs does not modulate tympanic responses to sound. AB - The effect of the opercularis (= middle ear) muscle on the acoustic responsiveness of the tympanic middle ear of anuran amphibians was studied using laser vibrometric measurements of tympanic responses to sound. Removal of the muscle or direct stimulation of denervated muscles had no measurable effects on tympanic responses to sound in either American bullfrogs (Rana catesbeiana) or green treefrogs (Hyla cinerea) at any frequency or at any sound-pressure level studied. These results suggest that, contrary to proposed hypotheses, the opercularis muscle of the anuran middle ear is not capable of modulating the responsiveness of the tympanic middle ear. Instead, the opercularis system most likely functions as an independent system involved in acoustic reception. PMID- 8201109 TI - Gerbil brain-stem auditory-evoked responses to maximum length sequences. AB - This study evaluated the feasibility of obtaining brain-stem auditory-evoked responses (BAERs) to trains of clicks with average rates of up to 500 clicks per second in the gerbil, in order to evaluate BAER behavior at rates higher than those possible in conventional averaging, and to evaluate whether these higher rates allow obtaining BAERs more efficiently. Gerbils were anesthetized with Nembutal, and normothermia was maintained with a homeothermic blanket system. Pseudorandom pulse trains, called maximum length sequences (MLSs), were generated by an Ariel DSP-16 board housed in an IBM-AT. Electrical activity was recorded with Grass needle electrodes placed subdermally. This activity was amplified and filtered by a Nicolet Compact Four, and digitized by the A/D of the Ariel DSP-16. Clicks were presented at levels of 50, 60, 70, 80, and 90 dB pSPL. Conventional BAERs were obtained at a rate of 30 Hz. MLS BAERs were obtained by presenting MLS pulse trains which were comprised of 64 pulses. Following collection of the response to MLS pulse trains, the MLS BAER was obtained by cross correlating the response with a recovery sequence. The minimum time between pulses is called the minimum pulse interval (MPI). MLS BAERs were obtained for MPIs of 6, 4, 2, and 1 ms. BAERs were obtained in ten young adult gerbils for all rate by click-level conditions. BAERs were observed in all animals for all click levels and rates. Generally, with increasing click level there were decreases in peak latencies and increases in peak amplitudes. With increasing rate (decreasing MPI), there were increases in peak latencies, increases in the i-iv interval, and decreases in peak amplitudes. Computations suggested the the most efficient rate (i.e., the rate producing a constant signal-to-noise ratio response in the least amount of time) is not necessarily the fastest rate, but depends on the BAER peak and click level. PMID- 8201110 TI - Conventional and cross-correlation brain-stem auditory evoked responses in the white leghorn chick: rate manipulations. AB - Rate-dependent changes in the chick brain-stem auditory evoked response (BAER) using conventional averaging and a cross-correlation technique were investigated. Five 15- to 19-day-old white leghorn chicks were anesthetized with Chloropent. In each chick, the left ear was acoustically stimulated. Electrical pulses of 0.1-ms duration were shaped, attenuated, and passed through a current driver to an Etymotic ER-2 which was sealed in the ear canal. Electrical activity from stainless-steel electrodes was amplified, filtered (300-3000 Hz) and digitized at 20 kHz. Click levels included 70 and 90 dB peSPL. In each animal, conventional BAERs were obtained at rates ranging from 5 to 90 Hz. BAERs were also obtained using a cross-correlation technique involving pseudorandom pulse sequences called maximum length sequences (MLSs). The minimum time between pulses, called the minimum pulse interval (MPI), ranged from 0.5 to 6 ms. Two BAERs were obtained for each condition. Dependent variables included the latency and amplitude of the cochlear microphonic (CM), wave 2 and wave 3. BAERs were observed in all chicks, for all level by rate combinations for both conventional and MLS BAERs. There was no effect of click level or rate on the latency of the CM. The latency of waves 2 and 3 increased with decreasing click level and increasing rate. CM amplitude decreased with decreasing click level, but was not influenced by click rate for the 70 dB peSPL condition. For the 90 dB peSPL click, CM amplitude was uninfluenced by click rate for conventional averaging. For MLS BAERs, CM amplitude was similar to conventional averaging for longer MPIs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201111 TI - A computer model of amplitude-modulation sensitivity of single units in the inferior colliculus. AB - A computer model is presented of a neural circuit that replicates amplitude modulation (AM) sensitivity of cells in the central nucleus of the inferior colliculus (ICC). The ICC cell is modeled as a point neuron whose input consists of spike trains from a number of simulated ventral cochlear nucleus (VCN) chopper cells. Input to the VCN chopper cells is provided by simulated spike trains from a model of the auditory periphery [Hewitt et al., J. Acoust. Soc. Am. 91, 2096 2109 (1992)]. The performance of the model at the output of the auditory nerve, the cochlear nucleus and ICC simulations in response to amplitude-modulated stimuli is described. The results are presented in terms of both temporal and rate modulation transfer functions (MTFs) and compared with data from physiological studies in the literature. Qualitative matches were obtained to the following main empirical findings: (a) Auditory nerve temporal-MTFs are low pass, (b) VCN chopper temporal-MTFs are low pass at low signal levels and bandpass at moderate and high signal levels, (c) ICC unit temporal-MTFs are low pass at low signal levels and broadly tuned bandpass at moderate and high signal levels, and (d) ICC unit rate-MTFs are sharply tuned bandpass at low and moderate signal levels and flat at high levels. VCN and ICC units preferentially sensitive to different rates of modulation are presented. The model supports the hypothesis that cells in the ICC decode temporal information into a rate code [Langner and Schreiner, J. Neurophysiol. 60, 1799-1822 (1988)], and provides a candidate wiring diagram of how this may be achieved. PMID- 8201112 TI - Single neurons in the frog inferior colliculus exhibit direction-dependent frequency selectivity to isointensity tone bursts. AB - The effects of sound direction on frequency selectivity of inferior colliculus (IC) neurons were investigated by measuring the neuron's isointensity frequency responses (FRs) to tone bursts emanating from a free-field loudspeaker at several sound levels. The loudspeaker was rotated across the frontal field at 0 degrees elevation through 180 degrees of azimuth (from contralateral 90 degrees or C90 degrees to ipsilateral 90 degrees or I90 degrees). At each frequency, to assess the magnitude of response change with sound direction, the mean spike count obtained at an azimuth was compared to that at C90 degrees. The FR of most IC neurons (75/83 or 90%) was direction dependent. For most of these neurons, bandwidths of FRs were narrower when sounds originated from ipsilateral azimuths. Remarkably, with a change in sound azimuth, some segments of these FRs showed very distinct changes in shape, while other portions of the same FRs remained essentially unchanged. These narrow-band changes associated with restricted portions of the FR, were also exhibited by neurons with direction-dependent frequency-threshold characteristics (Gooler et al., 1993). Additionally, the most frequent direction-dependent change in the FRs occurred in a narrow frequency band around the units' best excitatory frequency. PMID- 8201113 TI - Intensity resolution and loudness in high-pass noise. AB - Intensity resolution and loudness growth for a 1000-Hz tone were studied in the presence of high-pass noise (cutoff: 1800 Hz). Intensity resolution was measured for gated and continuous standards using a three-interval forced-choice (3-IFC) adaptive procedure. Loudness matches were obtained using an adaptive, alternate binaural loudness balance procedure. Three subjects listened in three conditions (1) quiet; (2) high-pass noise with a spectrum level of 32 dB SPL; and (3) high pass noise with a spectrum level of 42 dB SPL. Noise levels were selected so that detection thresholds were minimally affected at the test frequency; however, for frequencies in the noise passband, thresholds were shifted to either 50 or 60 dB SPL, depending on the spectrum level of the noise. On average, loudness growth and intensity resolution were unaltered by the presence of the noise for tonal levels below 40 dB SPL; above 40 dB SPL the following was generally true: (1) intensity resolution for gated standards was well described by Weber's law except at the highest levels where the Weber fraction decreased; (2) intensity resolution for continuous standards showed a "near-miss" to Weber's law, but just noticeable differences (jnd's) were slightly larger than those in quiet for the same SPL; (3) loudness was reduced. A comparison of jnd's for equally loud tones showed that loudness is less dependent on excitation spread than the jnd. That is, jnd's in the threshold-shifted ear were larger than the ones in quiet when the comparison was made for tones judged to be equally loud.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201114 TI - Profile analysis and comodulation detection differences using narrow bands of noise and their relation to comodulation masking release. AB - Experiment 1 examined the ability to compare relative level across frequency (profile analysis) for stimuli that were dynamically varying over time. The task was to detect an increment in level of a narrow band of noise (the target) in the presence or absence (reference condition) of four flanking bands (FBs). The envelopes of the FBs were either the same as that of the target (correlated condition), independent of that of the target but the same as each other (co uncorrelated condition), or all independent (all-uncorrelated condition). The overall level of the stimuli was either fixed or randomly varied from one stimulus to the next. The results showed that subjects can make effective use of spectral-shape cues even for stimuli whose amplitudes vary markedly over time. In the correlated condition, the threshold for detecting an increment in the level of the target band was decreased (relative to the reference condition) both when the overall level was fixed and when it was varied randomly from stimulus to stimulus. In the uncorrelated conditions, the FBs did not lead to better performance when the overall level was fixed; rather they produced a small interference effect. When the overall level was randomized, the presence of uncorrelated FBs produced thresholds that decreased with increasing bandwidth and, for a bandwidth of 64 Hz, produced an improvement in performance (relative to the reference condition) that was almost as large as that produced by the correlated FBs. It seems that the more rapid fluctuations in the wider bands of noise were smoothed by the auditory system, enabling information about the long term spectral shape to be extracted effectively. Experiment 2 used similar stimuli, but the task was to detect the target, rather than to discriminate its level. Detection thresholds in the presence of FBs were lowest in the co uncorrelated condition, higher in the correlated condition, and highest in the all-uncorrelated condition. Thus the presence of correlated FBs improved discrimination thresholds in the profile analysis task, but impaired performance in the detection task. Reasons for the discrepancy between the effects of correlated FBs in the two tasks are discussed in the context of the cues available to the listener. PMID- 8201115 TI - Effect of masker level on overshoot in running- and frozen-noise maskers. AB - Masked thresholds were measured with running- and frozen-noise maskers. The 5-kHz signal was 2 ms in duration. The masker was low-pass noise (20 Hz-10 kHz); its total duration was 300 ms. The overall level of the masker was 30, 50, or 70 dB SPL. The onset of the signal was delayed by 0, 3, 8, 18, 198, or 278 ms relative to the onset of the masker. In all frozen-noise measurements, the signal was added to the same fine structure of the noise. Overshoot in frozen noise was measured for two starting phases of the signal that led to a 10-dB difference for large signal-onset delays. In all three configurations (running noise and frozen noise with two different signal phases) masker level had a similar influence on overshoot. At the intermediate masker level (50 dB SPL), a significant amount of overshoot (up to 15 dB) was observed in all three conditions. At the low and the high masker levels, overshoot was very much reduced, and even became negative in most conditions for the 30-dB-SPL masker. For the 50-dB frozen-noise masker, the total variation of thresholds with signal phase was 8 to 11 dB for long signal onset delays, but only 3 to 6 dB for short delays. For the low- and high-level maskers, where only a small overshoot was observed, the threshold variation with phase for a signal at masker onset was the same as that for the long-delay condition. An explanation for the variation of signal detectability with masker level is proposed that refers explicitly to the compressive input-output characteristic of the basilar membrane at intermediate levels. PMID- 8201116 TI - Modulation detection and discrimination with three-component signals. AB - In an attempt to study the processing of amplitude and frequency modulation (AM and FM), detection and discrimination tasks using mixed modulation (MM) signals were performed. Modulation detection thresholds were obtained for three-component signals that span the parameter space between AM and quasi-FM. A single-cue modulation detection model predicts the thresholds with reasonable accuracy. If one assumes that the AM and FM components are extracted separately, thresholds are also well predicted if the d' of the MM signals is equal to the sum of the separate d's of the AM and FM components (two-cue summation model). This could arise from common internal noise that puts the AM and FM information along a single decision axis. A modulation discrimination task was then examined in which the subjects discriminate between signals with both different modulation depths and different modulation types. The single-cue model predicts performance well. In order for the two-cue model to predict the results, the AM and FM cues must be combined into a single statistic before a decision can be made; the listener cannot process the cues separately. PMID- 8201117 TI - Vibrotactile temporal masking: effects of multiple maskers. AB - Previous investigations of temporal masking effects in vibrotactile detection tasks have generally produced results suggesting considerable similarities in stimulus processing between the tactile system and the auditory system. Auditory presentation of combinations of maskers (e.g., two forward maskers) has yielded masking effects in excess of the level of masking predicted by a simple intensity sum of each masker's individual effect. This "additional masking" has led to predictions of compressive nonlinearities in auditory stimulus processing. In the present study, two experiments were conducted to investigate further temporal masking phenomena for the tactile system. In the first experiment vibrotactile temporal masking functions for single forward and backward maskers were generated to examine trade-offs among values of masker duration, masking intensity, and interstimulus interval to maintain constant detectability of a target. Results suggested that stimuli in very close temporal proximity to the target might follow somewhat different trading equations from those farther removed. Overall, results were consistent with previous findings of temporal integration in the tactile system, and support the notion of an energy integrating mechanism. In the second experiment, pairs of maskers were presented to determine whether additional masking effects occurred in vibrotactile detection. In contrast to findings for auditory presentation, in which all masker configurations generated additional masking, the tactile results showed substantial amounts of additional masking only for pairs of backward maskers. Several possible explanations for this results are evaluated, and results are discussed in terms of similarities and dissimilarities in auditory and tactile temporal processing. PMID- 8201118 TI - Acoustic correlates of [b] and [w] produced by normal young to elderly adults. AB - Various studies indicate that temporal characteristics of articulated subphonemic segments and syllables change as a function of age. The purpose of the present study was to investigate age-related changes in the production of a phonetic contrast--in particular that of the stop consonant [b] versus the semivowel [w]. Thirty-nine subjects with normal hearing and belonging to three age groups (20 30, 50-60, 70-80 years old) were tested. Acoustic analyses of the recorded syllables [b alpha] and [w alpha] indicated that duration of syllables, prevoicing, release, and vowel transition became significantly longer with the speaker's age, except for the vowel transition in the [w] context. However, acoustic cues, such as the difference in amplitude change in the vicinity of the release segment, were not sensitive to the effects of aging. PMID- 8201119 TI - A perceptual study of source coding of Fourier phase and amplitude of the linear predictive coding residual of vowel sounds. AB - A practical question in a Fourier transform coding of speech signals is to what accuracy their amplitude and phase spectra have to be represented without perceptible distortions. In this paper a concern is with the audibility of quantization noise signals which are produced by quantizing the amplitude and phase spectra of vowel sounds. Experiments show that the detection of the noise targets with maskers of a low fundamental frequency is determined mainly by the sharpest temporal resolution of the auditory system in the high-frequency region. For maskers of a high fundamental frequency the detection is determined mainly by the sharpest spectral resolution in the low-frequency region. Noise targets with global random phase and amplitude are relatively more difficult to detect than those produced by a local randomization. Local random phase noise targets are generally more detectable than those produced by local amplitude randomization. The relative importance of phase and magnitude spectra in the Fourier transform coding is strongly dependent on the fundamental frequency of the vowel sounds and the window size used in the short-time Fourier analysis. PMID- 8201120 TI - Production and perception of coarticulated tones. AB - In the present study, the distinctive tones of Mandarin were found to coarticulate with adjacent tones in running speech. However, the amount of deviation of a tone from its canonical form due to coarticulation varied depending on the nature of the tonal context. In a context where adjacent tonal values agree (a "compatible" context), the deviation was relatively small. In a context where adjacent tonal values disagree (a "conflicting" context), the deviation was much greater, sometimes even to the extent of changing the direction of a dynamic tone. To examine the perception of coarticulated tones, naturally produced words and phrases were used as stimuli for tone identification. However, their semantic information was removed through waveform editing while all the tonal information contained in the signal remained intact. Identification of tones in the compatible context was highly accurate with or without the original tonal context. Tonal identification for the conflicting context remained accurate only when the tones were presented with the original tonal context. Without the original context, i.e., in isolation, correct tone identification dropped below chance. When the original tonal context was altered, listeners compensated for the altered context as if it had been there originally. It thus seems that, in tone perception, listeners compensate for variations due to coarticulation. Nevertheless, even with the presence of the original context, perceptual identification was better for the compatible context than for the conflicting context, indicating that variation due to coarticulation is not always completely compensated for by listeners. PMID- 8201121 TI - An ultrasonic method for monitoring tongue shape and the position of a fixed point on the tongue surface. PMID- 8201122 TI - On coordinate systems and the representation of articulatory movements. PMID- 8201123 TI - The effects of age and sex on speech intonation and duration for matched statements and questions in French. PMID- 8201124 TI - Effects of spectral smearing on the intelligibility of sentences in the presence of interfering speech. PMID- 8201125 TI - The stability of depressed mood in young adolescents: a school-based survey. AB - To test the stability of self-reported depressed mood in a school-based sample of young adolescents, 268 schoolchildren completed two self-rating scales measuring depressed mood, the Depression Self Rating Scale and the Child Depression Inventory, at three timepoints over a period of 6 months. Depressed mood in the sample, as measured across the whole range of the scales, was reasonably stable. A subgroup of children was identified for whom the mean scores of both scales at all three timepoints was close to, or above, the cut-off points, representing a stably depressed mood similar to that found in clinical populations. The present findings indicate that depressed mood within a section of the general child population may be more stable and less transient than previously thought. PMID- 8201126 TI - Oral D-fenfluramine and neuroendocrine challenge: problems with the 30 mg dose in men. AB - Ten healthy male volunteers of normal weight received 30 mg of D-fenfluramine, a putative selective releaser of 5-hydroxytryptamine (5-HT), and placebo by mouth in balanced order at a 1 week interval after a light breakfast. Blood was taken for estimation of plasma cortisol and prolactin, and the patients completed self rating scales for stress and arousal and rated themselves on visual analogue scales for mood, hunger and alertness at appropriate time points from 30 min before to 300 min after drug/placebo ingestion. There were no statistically discernible effects of D-fenfluramine on either hormone measures or subjective ratings. The failure to find effects may be due to a too low dose of D fenfluramine and/or a lower sensitivity to the drug in men compared with women. More information is required on the dose/response relationship and drug absorption especially after food. However, the findings cast doubt on results already obtained employing this dose of the drug in studies that have included male subjects. Furthermore, the interpretation of earlier studies with D,L fenfluramine at a dose of 60 mg is also made more uncertain by the failure to confirm that the more selective D-isomer produces equivalent effects. PMID- 8201127 TI - A brief self-report depression measure assessing mood state and social impairment. AB - Many measures of depression severity appear confounded by including depressive sub-typing features. We report the design of a brief (11 item) self-report scale of depression severity (the AUSSI), assessing both mood state and social impairment domains, and designed to be independent of sub-typing features. Mood severity and functional impairment scores demonstrated some independence in a sample of 360 patients. Patients with a 'melancholic' depressive type (categorised by four differing systems) differed from residual 'non-melancholic' depressed patients by having higher impairment scores, but the assigned groups did not differ, in the main, by mood severity scores. Advantages of the measure are summarised. PMID- 8201128 TI - Symptomatology of affective and psychotic illnesses related to childbearing. AB - Symptom patterns in women with childbearing-related onset illnesses (CBROI) and nonchildbearing-related onset illnesses (NCBROI) were compared. Women with diagnoses of Affective Disorders and Psychoses (n = 762) were divided into four groups: CBROI with psychosis, CBROI with non-psychotic affective illnesses, NCBROI with psychosis, and NCBROI with non-psychotic affective illness. Principal components analysis of 64 symptoms revealed 9 factors. The most dramatic result was the high score for psychotic women with CBROI on the factor cognitive disorganization/psychosis. Psychotic women with CBROI also reported homicidal ideation more frequently. Symptoms of non-psychotic women with CBROI and NCBROI did not differ. PMID- 8201129 TI - Postpartum blues: relationship between not-protein bound steroid hormones in plasma and postpartum mood changes. AB - The relationship between non-bound steroid hormone levels in plasma and the occurrence of postpartum mood changes was investigated in 26 newly delivered mothers throughout the first 5 days postpartum. Studies with saliva samples had reported higher concentrations of 17 beta-estradiol and progesterone on the days of symptoms in women experiencing postpartum blues. As there had been a controversy as to how far saliva concentrations reflect free hormone levels in plasma, free hormone levels of 17 beta-estradiol and progesterone were determined in plasma using ultrafiltration. No significant difference concerning free hormone levels could be found between women with and without postpartum blues. PMID- 8201130 TI - Effects of morning light treatment on subjective sleepiness and mood in winter depression. AB - The effects of morning light treatment on mood, subjective sleepiness and body temperature were investigated with 13 outpatients with winter depression and 13 healthy controls. Bright light for 1 h daily for 2 weeks resulted in a significant reduction in depression ratings and evening subjective sleepiness in the patients compared with the healthy controls. Even a short 15-min exposure to light daily produced these changes. PMID- 8201131 TI - Diversity, African American students, and the college campus: perspective and challenge. PMID- 8201132 TI - The health status of African American college students: a literature review. AB - African American college students represent 1.3 million of the 14 million students currently enrolled in postsecondary institutions in the United States, but research specifically investigating or addressing the health status of these young people is rare. The author reviews the literature that has examined components of the social, mental, and physical health of African American college students. This literature review indicates a need for more information and for further research that specifically addresses health behaviors and practices of African American and other minority students. Health educators must recognize the importance of knowing about and understanding the mechanisms that support unhealthy as well as healthy behaviors in different cultural and ethnic groups. PMID- 8201133 TI - African American college students' health behaviors and perceptions of related health issues. AB - The authors identify specific health-related behaviors of African American college students and compare them with the students' perceptions of corresponding health issues. Among students surveyed, the rate of cigarette smoking (4%) was very low compared with smoking rates found in a national survey (14%); but alcohol consumption was relatively high (63%), although lower than the national average of 91%. More men than women smoked, but more women than men reported they drank alcoholic beverages. Most students (90.2%) said they did not usually eat breakfast, 73.6% reported that their diets were not nutritionally balanced, and the majority (55.4%) were not involved in daily physical activity. More than half (63%) of the students reported satisfactorily handling stress, and 74.1% indicated that they were sexually active. Respondents perceived the most important health issues facing college students as HIV/AIDS and sexually transmitted diseases (STDs), birth control, date rape, stress management, suicide, and alcohol and other drugs. PMID- 8201134 TI - Challenging heterosexism in college health service delivery. AB - The empowerment and affirmation of lesbian, bisexual, and gay students is long overdue. This article explores how human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), substance abuse, violence and hate-related crimes, suicide, and heterosexism all adversely affect the physical and emotional health of nonheterosexual college students. College health services must expand their current scope and practice and assume a leadership role in combating all forms of oppression by actively incorporating and addressing the unique health issues and needs of the lesbian, bisexual, and gay population. This article provides a brief overview of the relevant healthcare issues for lesbians, bisexuals, and gays; examples of heterosexism in college health services; and recommendations for institutional and personal and professional change. PMID- 8201135 TI - A model for HIV risk reduction and prevention among African American college students. AB - Training African American student leaders as peer educator-mentors to reach African American students in the traditional workshop setting as well as in informal, one-to-one occasions is an effective method of managing students' risks of human immunodeficiency virus (HIV) infection. The Ujima project, developed and implemented by Syracuse University Health Services, trained educator-mentors to provide first-year African American students with correct information about HIV risk reduction and how to build life skills associated with prevention that enhance self-esteem and provide ongoing social support on formal and informal occasions in a culturally sensitive manner. These strategies were successful in changing knowledge, attitudes, and behaviors necessary for HIV prevention among African American college students. PMID- 8201136 TI - The student health center as multicultural catalyst. AB - Stanford's student health center participated with underrepresented students in observing Black Liberation Month; Bisexual, Gay, and Lesbian Awareness Days; and Cinco de Mayo, the commemoration of a Mexican Army defeat of the French in 1862. For minority students on a campus where a majority of the students and faculty are White, the health center's involvement in these events was viewed as an affirmation and acceptance of worth of these diverse student groups. The outreach effort exposed health center caregivers to the cultures of the three groups when staff members attended the special activities, interacted with the celebrants, and became more sensitized to their needs. PMID- 8201137 TI - Perspectives on creating multicultural campuses. PMID- 8201138 TI - African American students' awareness of sickle cell disease. PMID- 8201139 TI - Protocol for acute and chronic sinusitis. AB - Formal protocols for nurse practitioners are mandated by many states. Protocols are of two types--process-oriented, which describe the steps used in treating patients, and disease-oriented, which define disease, explain etiology, and describe the plan of care, among other things. The sinus protocol outlined in this article is used in the UCLA student health service. It is disease oriented and focuses on college students, but it can also be adapted to use in a different setting. PMID- 8201140 TI - Flight simulator performance of younger and older aircraft pilots: effects of age and alcohol. AB - OBJECTIVE: To determine if older pilots forgot more about a learned flight task after a 10-month delay than did younger pilots and if the anticipated greater skill loss led older pilots' performance to be more disrupted by alcohol. DESIGN: Repeated measures comparative group design examining the effects of alcohol versus placebo in two age groups (younger and older) and at two timepoints: acute intoxication, at a Blood Alcohol Concentration (BAC) of 0.10%, and 8 hours post drink. SETTING: University medical center research laboratory. SUBJECTS: Fourteen younger (mean age = 27; SD = 4.21; range 21-34) and 13 older (mean age = 60; SD = 6.27; range 51-69) pilots, recruited from local flying clubs, with current FAA medical certificates. METHODS: We examined the effects of alcohol versus placebo in the two age groups and at two times, ie, acute intoxication (target BAC 0.10%) and 8-hour post-drink. Subjects flew a Frasca 141 simulator in a flight task that they had previously learned but not practiced for several months. After completing a baseline flight, pilots were tested during either an alcohol or a placebo condition at the two timepoints. The main outcome measure was a composite measure of flight performance based upon the mean of eight component standardized scores from different aspects of the flight task. RESULTS: We found detrimental effects of alcohol on the main outcome measure both at the acute and 8-hour post drink testing. There was also no significant difference between the older and younger pilots' performance of the flight task or in susceptibility to alcohol either while intoxicated or during hangover. CONCLUSIONS: This study replicates the findings of earlier studies that an 8-hour waiting period from "Bottle-to Throttle" is insufficient but finds little difference according to age in recollection of a previously learned task or in susceptibility to either acute or hangover effects of alcohol. PMID- 8201141 TI - Causes of weight loss in a community nursing home. AB - OBJECTIVE: To determine the causes of weight loss in nursing home residents. DESIGN: Retrospective chart review of all weights over the previous 6 months and an in-depth examination of all residents who lost 5 or more pounds over that period. SETTING: A for-profit community nursing home in an urban area. SUBJECTS: All residents who had been in the nursing home for 3 or more months. Their mean age was 80.1 years, and 89% were female. RESULTS: Weight loss of 5 pounds or more occurred in 19% of subjects. Only 15% of subjects had lost 5% of body weight, and 4% had lost more than 10% of their body weight. Depression accounted for 36% of the weight loss. Other causes of anorexia included medications, psychotropic drug reduction, swallowing disorders, paranoia, dementia with apraxia, gallstones, and obsessive-compulsive disorder. Increased energy utilization as a cause of weight loss was seen in two residents who wandered incessantly, one with tardive dyskinesia and one with chronic obstructive pulmonary disease. Dehydration was the cause of weight loss in two residents, and one resident had international weight loss for obesity. Cancer was the cause of weight loss in two residents. Four of 30 residents had more than one cause of weight loss. One of 25 tube-fed residents displayed weight loss. CONCLUSIONS: A single cause of weight loss can be identified in most nursing home residents. Depression is the most common cause of weight loss. Psychotropic drug reduction may cause weight loss. The majority of causes of weight loss in a community nursing home are potentially treatable. PMID- 8201142 TI - Safety assessment for the frail elderly: a comparison of restrained and unrestrained nursing home residents. AB - OBJECTIVE: To facilitate clinicians' judgement concerning physical restraint decisions by identifying potentially reversible injury risk factors that differentiate representative samples of restrained and unrestrained nursing home residents. DESIGN: Comparison of restrained and unrestrained nursing home residents on a safety assessment for the frail elderly (SAFE) protocol. SETTING: Long-term care facilities in the Greater Los Angeles Area. PARTICIPANTS: One hundred eight physically restrained and 111 unrestrained nursing home residents. INTERVENTION: None. MAIN OUTCOME MEASURES: (1) Internal, Interrater, and test/retest reliability of the overall SAFE protocol and of the four major factors measured by SAFE; (2) The relationship of SAFE scores to expert judgment of resident injury risk; (3) Differences between large samples of restrained and unrestrained residents on specific SAFE score factors. RESULTS: Two walking, one transition, and one judgment factor are reliably measured by the SAFE protocol. SAFE scores were significantly correlated with expert judgment of risk for injury and showed large differences between restrained and unrestrained residents, even after differences in ambulation ability between the two groups were accounted for. CONCLUSION: The SAFE is a reliable protocol that measures behavioral factors related to falls and risk for injury among nursing home residents with a broad range of cognitive impairment. Factors that significantly differentiate restrained and unrestrained groups should be targeted for rehabilitation and remediation in physical restraint reduction efforts. Removing or changing restraints for the large sample (50%) of restrained residents who were not ambulatory will not significantly increase their mobility, since the majority of this group could not independently propel their wheelchairs. Increased mobility for the large group of both restrained and unrestrained residents will likely be realized only if restraint reduction programs are combined with interventions to improve both mobility and the specific behavioral performance factors measured by SAFE. PMID- 8201143 TI - Caudal epidural blocks for elderly patients with lumbar canal stenosis. AB - OBJECTIVE: To determine the efficacy of caudal epidural blocks (CEB) in relieving pain and the duration of pain relief with CEB in elderly patients suffering from degenerative lumbar canal stenosis (LCS). DESIGN: This study was a descriptive, prospective study with a 10-month follow-up. PARTICIPANTS AND SETTING: Thirty patients, 76 +/- 6.7 years of age, with leg discomfort with or without back pain and with LCS documented by magnetic resonance imaging (MRI) within 1 year of the study, were recruited from the outpatient clinic of the Cleveland Clinic Florida. None of the subjects had received CEB or surgery for their leg discomfort and none had relief of pain by analgesics alone. MEASUREMENTS AND INTERVENTIONS: Subjects received a total of three doses of 0.5% Xylocaine with 80 mg Depo-Medrol into the caudal epidural space through the sacral hiatus at weekly intervals. The Roland 5-point pain rating scale was utilized before and at 2-month intervals up to 10 months after the CEB was administered. MRI was used to identify the degree of LCS. RESULTS: The degree of LCS on admission was moderate in 66.7% (n = 20) of the patients, mild in 23.3% (n = 7), and severe in the remaining 10% (n = 3). Patients had LCS involving 2.4 +/- 0.49 lumbar vertebrae. The degree of LCS is directly correlated with the pain level before CEB. After CEB, the pain level changed from 3.43 +/- 0.82 to 1.5 +/- 0.86 (P < 0.0000), with a significant relief of pain up to 10 months (the end of observation). The duration of pain relief ranged from 4 to 10 months (P < 0.0001). CONCLUSION: CEB offers significant pain relief and appears to be a reasonable therapeutic option among elderly patients with LCS. This alternative seems particularly important among patients with poor response to drug therapy and who are either poor surgical risks or who have refused surgery. PMID- 8201144 TI - Mortality differences between elderly Mexican Americans and non-Hispanic whites in San Antonio, Texas. AB - OBJECTIVE: To identify differences in causes of death between elderly Mexican Americans (MA) and non-Hispanic whites (NHW). DESIGN: Retrospective death certificate review. SUBJECTS: Elderly Mexican Americans and non-Hispanic Whites age 65 and over who died in Bexar County, Texas during 1989. MEASURES: Data obtained from chart review included age, sex, race/ethnicity, and cause of death. Age-adjusted and cause-specific mortality rates, odds ratios (OR), and 95% confidence intervals (CI) were calculated. RESULTS: Mexican Americans were at greater risk of dying in nine of the thirty causes of death examined. The mortality rates of MA subjects were higher than those of NHW from death caused by diabetes (OR = 3.19, CI = 2.27-4.49), renal failure (OR = 2.06, CI = 1.44-2.94), congestive heart failure (OR = 1.50, CI = 1.44-2.94), and multiple systemic diseases (OR = 2.59, CI = 1.89-3.57). Among the male subjects, MA had a greater risk than NHW of dying from myocardial infarction (OR = 1.83, CI = 1.15-2.90), coronary disease (OR = 1.37, CI = 1.07-1.75) and septicemia/pyuria (OR = 2.12, CI = 1.09-4.10). Among female subjects, MA had a greater likelihood of dying from cirrhosis (OR = 3.03, CI = 1.00-9.29). For only one of the causes of death was the risk lower among MA than NHW: MA female subjects had a lesser chance of dying from the chronic obstructive pulmonary disease (COPD) than NHW females (OR = 0.36, CI = 0.18-0.72). CONCLUSION: Mexican American elders have a greater risk of dying from non-insulin dependent diabetes mellitus and renal failure than their NHW counterparts. Elderly MA men have a greater risk of dying from cardiovascular disease than their NHW counterparts. Mexican American women may have a greater risk of dying from cirrhosis, but a lower risk of dying from complications of COPD. Finally, death from ill defined causes, such as multiple systemic diseases, may be a major under-acknowledged cause of death among older MA. PMID- 8201145 TI - Blinking and the release reflexes: are they clinically useful? AB - OBJECTIVE: To review the clinical utility of blinking and the release reflexes, palmomental, glabellar, grasp, and snout, as an important part of the bedside neurological examination. DESIGN: Articles published from 1966 to 1993 that addressed blinking or the release reflexes were identified by searching the MEDLINE database. Thirty-seven references provided clinically useful and applicable information. RESULTS: There is controversy regarding the optimal method of clinical elicitation of these reflexes. The release reflexes are frequently seen as an incidental abnormality in the elderly. A positive grasp reflex, especially if asymmetrical, is sensitive but not specific for abnormal brain function. Lack of habituation is more important than the mere presence or absence of a reflex. The brainstem circuits involved in the regulation of blinking and the release reflexes are discussed, as are their abnormalities in a variety of clinical settings. CONCLUSION: Blinking and the release reflexes have clinical utility in the diagnosis and bedside clinical assessment of diseases as diverse as frontal lobe lesions, hydrocephalus, multiple sclerosis, Parkinson's disease, Alzheimer's disease and other dementias, falls in the elderly, ageing, HIV-encephalopathy, schizophrenia, tumors in the region of the sylvian aqueduct and recovery from head trauma. PMID- 8201146 TI - Fracture risk in patients with Alzheimer's disease. AB - OBJECTIVE: To assess the risk of fracture following onset of Alzheimer's disease. DESIGN: Retrospective (historical) cohort study. SETTING: Population-based in Rochester, Minnesota. PARTICIPANTS: All 543 Rochester residents with onset of Alzheimer's disease during the 10-year period, 1975-84, and an equal number of age- and sex-matched controls from the community. MEASUREMENTS: Fractures were assessed through review of each subject's complete (inpatient and outpatient) medical records in the community. MAIN RESULTS: Rochester residents with Alzheimer's disease were no more likely to have a history of fracture prior to onset than were matched controls from the same population. During the year of onset, there was a 2-fold excess of fractures at various sites among those with Alzheimer's disease. The risk ratio for any fracture subsequently was 1.1 (95% CI 0.9, 1.3), and this slight increase was accounted for entirely by a 2.7-fold increase in the risk of hip fracture (95% CI 1.8, 4.2). CONCLUSIONS: Fracture risk was not increased before the onset of Alzheimer's disease, although there was an excess of fractures around the time that Alzheimer's disease came to clinical attention. Fracture risk was not elevated thereafter except for a substantial increase in the risk of hip fracture. This suggests a link with certain falls rather than generalized disuse osteoporosis. PMID- 8201147 TI - Voluntary active euthanasia and physician-assisted suicide in Dutch nursing homes: requests and administration. AB - OBJECTIVE: To learn how many requests for voluntary active euthanasia and/or physician-assisted suicide (EAS) are made to Dutch nursing home physicians (NHPs) and how often these requests are honored. DESIGN: Retrospective survey. SETTING: The Netherlands. PARTICIPANTS: All Dutch NHPs affiliated with the Dutch Association of Nursing Home Physicians (n = 713). MEASUREMENTS: An anonymous postal questionnaire was sent to all Dutch NHPs affiliated with the Dutch Association of Nursing Home Physicians (n = 713). Respondents were asked how often they had received an explicit request for EAS and whether they had complied with that request. Those who had complied were asked questions about the last occasion on which they had administered either voluntary active euthanasia or physician-assisted suicide. RESULTS: The response rate was 86% (n = 582). Of the respondents, 88% had never administered EAS in nursing homes. The remaining 12% (n = 69) had received 164 requests for voluntary active euthanasia and 53 requests for physician-assisted suicide in the period 1986 through mid-1990. Of these requests, 74 were granted (51 voluntary active euthanasia and 23 physician assisted suicide). Dutch NHPs together receive an average of 300 requests for EAS a year. They comply with 25 of such requests annually. CONCLUSION: Not many requests for EAS are made in Dutch nursing homes. Of these requests, fewer than 1 in 10 result in the actual administration of EAS. The data presented are relatively constant for the 4.5-year period studied. PMID- 8201148 TI - Voluntary active euthanasia and physician-assisted suicide in Dutch nursing homes: are the requirements for prudent practice properly met? AB - OBJECTIVE: To acquire data about and an understanding of the way in which Dutch nursing home physicians (NHPs) who administer voluntary active euthanasia and/or physician-assisted suicide (EAS) cope with the requirements for prudent practice. These requirements include: the patient must experience his or her suffering as unbearable and hopeless; the wish to die must be well considered and persistent; the request must be voluntary; the NHP must consult at least one other physician; the physician is not allowed to issue a certificate testifying to natural death and is obliged to keep records. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: See preceding paper. RESULTS: Sixty-nine NHPs (12%) indicated that they had administered EAS on at least one occasion. The state of the patient was described by the NHP as utterly hopeless in 88% of cases and as utterly unbearable in 64% of the cases. The period of time between the first discussion of the subject and the actual administration varied from less than a day to more than a year. The most frequently given reasons for the request were unbearable suffering (53%) and hopeless suffering (49%). The majority of the NHPs (85%) indicated that it was the patient who first broached the subject of EAS. Eighty-five percent of the NHPs also requested a consultation with another physician. In the majority of cases this second opinion was given by another NHP (63%); over 50% of these NHPs worked in the same nursing home. Ninety-one percent of the physicians consulted were convinced that the request was well considered, and 93% found that there was no alternative treatment available. The nurses involved were consulted informally: 94% were questioned about the request for EAS and 93% about the physician's intention to comply. Seventy-five percent of the respondents said they had made some sort of written notes regarding the last time they had administered EAS. The number of certificates testifying to death by natural causes fell after 1988. In 41% of the cases all requirements were met. CONCLUSION: The results of this study indicate that Dutch NHPs observe all the requirements for EAS in 41% of cases. In the remaining cases, shortcomings were found: NHPs allowed too little time between the first discussion and the actual administration; they did not always keep written records; or they signed a death certificate testifying that the patient had died a natural death. PMID- 8201149 TI - An in-home preventive assessment program for independent older adults: a randomized controlled trial. AB - OBJECTIVE: To evaluate the effectiveness of in-home geriatric assessments as a means of providing preventive health care and improving health and functional status of community-living elderly veterans. DESIGN: Randomized controlled trial with 1-year follow-up. SETTING: Home visits performed in a suburb of Los Angeles. PARTICIPANTS: Community-living veterans 70 years and older not currently receiving health care at the Sepulveda VA Medical Center (n = 131 intervention; 123 controls). INTERVENTION: A home visit by a physician's assistant or nurse, to screen for medical, functional and psychosocial problems, followed by a letter describing findings and recommendations, and follow-up visits by trained volunteers at 4-month intervals for 1 year. Controls received only telephone interviews at 4-month intervals to collect outcome data. MEASUREMENTS: Compliance with recommendations was studied for the intervention group. Outcome comparisons between the two groups included: mortality, medication usage, functional status, immunization rates, and nursing home and hospital utilization. MAIN RESULTS: A mean of four new or suboptimally treated problems was identified for intervention subjects. Subjects complied with 76% of recommendations to see a physician or initiate a specific health practice. At 12-month follow-up, intervention subjects had significantly increased their immunization rates (P < 0.001) and had a significantly increased likelihood of having a primary care physician (P < 0.05). Twelve-month functional status (IADL) scores were significantly higher for intervention subjects than for controls; intervention subjects maintained their functional status, while controls experienced significant decline during the follow-up year (P < 0.05). Non-prescription drug use increased significantly among controls, but not among intervention subjects (P < 0.05). CONCLUSIONS: A brief geriatric screening assessment performed in the home can detect unrecognized and treatable problems, even among relatively healthy older adults. The use of trained volunteers is a feasible strategy for providing health education and follow-up contacts. These results support the concept that preventive gerontological approaches can help maintain important aspects of health and function. PMID- 8201150 TI - Pyrazolopyridine derivative acts as a novel cyclooxygenase inhibitor: antiplatelet effect in aged patients with ischemic stroke. AB - OBJECTIVE: To examine the antiplatelet effect of a novel pyrazolopyridine derivative (KC-764) in geriatric patients with ischemic stroke. DESIGN: Randomized clinical trial of three graded dose levels. SETTING: A geriatric clinic attached to a nursing home. PATIENTS: Fifteen patients with a history of cerebral infarction with a mean age of 75 +/- 5 years (range, 65-83). Patients were divided into three groups and administered 10, 20, or 40 mg/day KC-764 for 8 weeks. MEASUREMENTS: Platelet aggregation induced by arachidonate, ADP, collagen and platelet-activating factor. Plasma or serum levels of thromboxane B2 and 6 ketoprostaglandin F1 alpha. MAIN RESULTS: Platelet aggregation was inhibited by KC-764 administration and returned to the control level after discontinuation. Although plasma thromboxane B2 levels were markedly decreased, plasma 6 ketoprostaglandin F1 alpha was not affected. However, the dose of 10 mg/day was not sufficient to maintain an effective plasma level of KC-764. There were no side effects or changes in laboratory findings. CONCLUSIONS: We confirmed that KC 764 at a dose of 20 to 40 mg/day is an effective antiplatelet agent and a good candidate for a trial to see if it is feasible for long-term use for the prevention of ischemic stroke in high-risk patients. PMID- 8201151 TI - The PACE pilot study: 12-month results and implications for future primary prevention trials in the elderly. (Prevention with low-dose Aspirin of Cardiovascular disease in the Elderly) AB - OBJECTIVE: To document compliance with medication, drop-out and drop-in rates, and baseline cardiovascular event rates during the pilot phase of the PACE (Prevention with low-dose Aspirin of Cardiovascular disease in the Elderly) study. DESIGN: Randomized, double-blind, placebo-controlled trial of low-dose aspirin therapy. SETTING: Community-based, in general practices and residential retirement villages, in Victoria, Australia. SUBJECTS: Four hundred persons aged 70 years and older (53% females), ambulatory and living independently, who volunteered to participate. None had significant vascular disease, peptic ulceration, hemorrhagic symptoms, or were currently taking non-steroidal anti inflammatory drugs. MAIN OUTCOME MEASURES: Compliance with medication (assessed by pill count and platelet function tests), self-reported drop-out and drop-in rates, and incidence of cardiovascular events reported by participants and their general practitioners during a 12-month period. RESULTS: Two fatal cardiovascular events, three non-fatal coronary events, and eight non-fatal cerebrovascular events were observed during the 12-month period. These incidence figures were approximately 15%, 15%, and 40%, respectively, of those in the general population of the same age and sex, based on morbidity data available from the Australian Bureau of Statistics. Compliance to medication was excellent (87%), and premature withdrawal (other than for a study end point) was limited to 14.5%. Secondary 'softer' endpoints, such as transient ischaemic attack and unstable angina, necessitated patient withdrawal from randomized therapy and possibly contributed to the small number of primary 'hard' end points observed. The projected power of the main study to detect a 20% treatment effect on overall cardiovascular mortality in 15,000 subjects over a 4-year period may, therefore, be substantially reduced. CONCLUSIONS: These results suggest that any future primary prevention study of cardiovascular disease in the elderly examining the effect of low-dose aspirin on overall cardiovascular mortality will likely need to use much larger numbers of patients or use a combined end point of fatal and non-fatal ischemic events. PMID- 8201152 TI - Multiple myeloma in the elderly. AB - While multiple myeloma is an incurable disease for nearly all patients, current chemotherapy and supportive care can result in significant disease control and improved duration of survival and quality of life. With the average age of patients about 70, most of the high-dose curative strategies exclude the bulk of patients affected by the disease. Recent advances in understanding the biology and pathophysiology of myeloma have led to novel therapies aimed at altering drug resistance, improving duration of the plateau phase, interrupting the cytokine growth stimulation, and improving management of common complications including infections, anemia, and bone lesions. These latter approaches are not restricted to younger patients, and early evidence indicates that elderly patients are also likely to benefit. PMID- 8201153 TI - Guidelines, practice policies, and parameters: the case for geriatrics. AB - OBJECTIVE: As the population ages, the care of older persons becomes more important. At the same time, practice guidelines that provide recommendations for appropriate care are being published in greater numbers. The purpose of this work is to determine the proportion of guidelines that contain specific information about older persons. DESIGN: Through a random sample of published guidelines listed in the AMA Directory of Practice Parameters, 1992 Edition, we determined the proportion of guidelines that contain specific age-related information. We also determined if, over time, there was a difference in the proportion of practice guidelines containing information about older persons. RESULTS: 45.9% (95% CI, range 33.4-58.4) of guidelines that could conceivably pertain to older persons contain no age information; 24.6% (95% CI, range 13.8-35.4) of guidelines contain information only about persons less than 65 years of age; 29.5% (95% CI, range 18.1-41.0) of guidelines contain specific information about older persons. Moreover, there were no secular trends in the proportion of guidelines pertaining to older persons. CONCLUSIONS: Only a minority of practice guidelines contain information about older persons. Possible causes and solutions to this shortfall are discussed. PMID- 8201154 TI - The crash of an 83-year-old civilian pilot in upstate New York. PMID- 8201155 TI - Physician-assisted death in The Netherlands and the United States: ethical and cultural aspects of health policy development. PMID- 8201156 TI - Alzheimer's disease: treatment research finds new targets. PMID- 8201157 TI - The trials and tribulations of clinical trials in the elderly. PMID- 8201158 TI - Trains, planes, and automobiles. PMID- 8201159 TI - Age 60 rule for retirement of airline pilots. PMID- 8201160 TI - Physician participation in nursing home care. PMID- 8201161 TI - Nursing home residents who are unsafe smokers and require supervision while smoking. PMID- 8201162 TI - 6 x 1 = 1: at last. PMID- 8201163 TI - High myopia, ocular assessment and patient education. PMID- 8201164 TI - Contact lens fitting should not be delegated to technicians. PMID- 8201165 TI - A comparative study of techniques for decreasing contact lens storage case contamination. AB - BACKGROUND: Contact lens storage cases may harbor a variety of pathogenic organisms, and are a potential source of ocular infection. In this study, we evaluated the anti-microbial efficacy of several methods of rinsing of contact lens storage cases. METHODS: Lens cases were inoculated with Pseudomonas aeruginosa and then 1) rinsed with hot tap water and closed without drying, 2) rinsed with hot tap water followed by air drying, 3) rinsed with 3% hydrogen peroxide followed by air drying, or 4) left closed and undisturbed (control condition). After 24 hours, the cases were cultured to determine the rate of disinfection. RESULTS: The hydrogen peroxide rinse was the most effective (99.5 percent of cases disinfected), followed by hot water with air drying (94.7 percent) and hot water without drying (51.1 percent). Significant residual hydrogen peroxide was detected in the cases rinsed with peroxide. CONCLUSIONS: Therefore, we recommend that patients be instructed to rinse their cases with hot water and allow them to air dry after use, as well as replace their cases on a regular basis. PMID- 8201166 TI - Daily disposed hydrogel lenses--a comparison with biweekly replacement. AB - BACKGROUND: Hydrogel lenses worn daily and disposed of daily represent an extreme of the spectrum of prescribing that has not been extensively investigated. This study was undertaken to ascertain whether hydrogel lenses worn on a daily replacement schedule displayed differences in patient comfort, vision, and physiological response and as compared to lenses replaced biweekly. METHODS: Hydrogel lens wearing schedules were devised to allow the patient to, in a masked fashion, directly compare the characteristics of a 1-day-old hydrogel lens to that of one 2 weeks old. Eighteen qualifying subjects wore Bausch & Lomb Seequence 2 lenses in this investigation. RESULTS: There was neither a significant difference in visual acuity, lens condition, and corneal or bulbar conjunctival fluorescein staining, nor a significant difference in subjective ratings of wearing comfort and clarity of vision between the 1-day and biweekly worn lenses. CONCLUSIONS: No apparent advantage was found in replacing the evaluated hydrogel lenses on a daily vs. biweekly schedule when considering vision, comfort, and physiological response of the eye. PMID- 8201167 TI - Oxygen performance of a prototype nonconventional hydrogel. AB - INTRODUCTION. Oxygen permeability (Dk) of available hydrogel materials used for soft contact lenses is currently restricted by the oxygen permeability of water at 80 Dk units. A predicted upper limit for conventional hydrogels amenable for use as a contact lens, has been 37 Dk units obtained with a water content of 80%. Methods for increasing oxygen permeability beyond that determined by water content must be explored, in order to further advance the physiological compatibility of hydrogel contact lenses. METHODS: Oxygen transport characteristics of a prototype nonconventional hydrogel contact lens material were derived in terms of human equivalent oxygen percentage (EOP) and thickness (L). The oxygen permeability of the material and oxygen transmissibilities (Dk/L) of various thicknesses were computed on the bases of a recently published nonlinear EOP vs. Dk/L relationship. RESULT: The material's oxygen permeability (Dk) was determined to be approximately 35 Dk units compared to 12.7 Dk units calculated for a conventional gel material having the same water content (52% H2O). Oxygen permeability equivalent to that obtained with high-water conventional gels was achieved using this mid-water nonconventional hydrogel. The prototype material was apparently also capable of low critical thicknesses typical of low-water conventional gels. DISCUSSION: Should new gel materials be durable with critical thicknesses in the "ultra-thin" range, nonconventional gel lenses could be capable of super and perhaps even hyper transmissibility with central minus lens EOP between 15-18.5% and Dk/L between 50-90 Dk/L units. The conventional relationships between water content and oxygen transmissibility of hydrogel contact lenses appear to have been surpassed. However, significant additional hurdles have yet to be overcome before nonconventional hydrogel materials can be ready for the ophthalmic marketplace. PMID- 8201168 TI - Review of the risk of HIV infection through corneal transplantation in the United States. AB - BACKGROUND: Human immunodeficiency virus (HIV), the pathogen that causes acquired immunodeficiency syndrome (AIDS), has been isolated in the corneal epithelium of some HIV-positive patients. This observation raises concern about the risk of HIV transmission through corneal transplantation surgery (penetrating keratoplasty). METHODS: A comprehensive review of the literature of the ocular transmission of HIV, screening of donor corneas, and the potential of HIV transmission through penetrating keratoplasty was conducted and analyzed to review and interpret the relative risk of HIV infection through corneal transplantation. RESULTS: No cases of HIV transmission were found as a result of routine eye care or ophthalmic surgical procedures, including HIV-serp-negative recipients who inadvertently received HIV-seropositive corneas. CONCLUSIONS: While ocular transmission of HIV appears to be remote, there are still relative risks of HIV transmission due to ophthalmic surgical procedures. Careful screening of donors for HIV infection affords an important increase in the margin of safety for corneal transplantation recipients. PMID- 8201169 TI - Rigid gas permeable extended wear (RGPEW) for the postoperative patient: a review and clinical observations. AB - BACKGROUND: Contact lenses are often the indicated method of correction following cataract extraction without implantation of an intraocular lens and following penetrating keratoplasty. Unfortunately, many patients who stand to benefit from contact lens wear are unable or lack the motivation to perform proper lens hygiene. Thus, extended lens wearing schedules using soft and rigid lens designs are often utilized. METHODS: Following a review of the literature regarding extended wear rigid lenses (PMMA and oxygen permeable) for the aphakic patient, this paper presents results of fitting high DK (92 x 10-11) rigid contact lenses worn from 1-2 months prior to removal on 11 patients (six with aphakia, five following penetrating keratoplasty). All subjects with aphakia were considered to be unsuccessful with soft aphakic extended wear (SEW). Subjects in the penetrating keratoplasty group were new to contact lens wear. RESULTS: These data show that 60 percent of aphakic patients considered to be unsuccessful with SEW may be successful with rigid gas permeable extended wear (RGPEW). The predicted success with RGPEW following penetrating keratoplasty was lower at 20-40 percent. CONCLUSIONS: RGPEW should be considered for the postoperative patient who stands to benefit from the optical advantages of contact lenses but is unable or not motivated to perform the necessary lens hygiene. Patients who experience lens awareness or become intolerant to SEW due to corneal edema are potential candidates for RGPEW. PMID- 8201170 TI - The ocular signs and symptoms of chronic fatigue syndrome. AB - BACKGROUND: Chronic Fatigue syndrome (CFS) is a relatively newly defined clinical entity that affects multiple systems including the ocular system. These effects have not been well documented. METHODS: 25 consecutive CFS patients were evaluated and the ocular signs and symptoms were described. RESULTS: Significant ocular symptoms were present in all 25 patients. The most common clinical findings were abnormalities of the preocular tear film and ocular surface (19 patients) and reduced accommodation for age (18 patients). CONCLUSIONS: CFS affects the ocular system in many ways. Eye care practitioners should pay particular attention to accommodative needs, ocular surface disease and tear film dysfunction when examining these patients. Further research into the pathophysiology of these ocular findings may lead to a better understanding of the pathophysiology of CFS. PMID- 8201171 TI - Contact lenses in the geriatric patient. AB - Contact lenses in the elderly patient are often prescribed for visual correction and/or corneal rehabilitation. The success of contact lenses in the geriatric patient is often limited by such factors as abnormal adnexal physiology, decreased manual dexterity, high degrees of refractive error, and low vision. Assessment of these factors prior to contact lens fitting can greatly increase the success of these unique contact lens applications. Indications and contraindications for contact lenses in the elderly, the need for special lens handling and care by family members, and available specialty lenses will be discussed. PMID- 8201172 TI - Clinical evaluation of primary peripheral cysts of the iris. AB - BACKGROUND: Peripheral primary cyst of the iris is an uncommon benign condition that may masquerade as a tumor of the ciliary body. Careful examination utilizing the slit lamp and gonioscopy is necessary to successfully differentiate the two. CONCLUSIONS: Given their uncommon occurrence and the importance of ruling out melanoma or other malignancies, this review is a guide in the evaluation and diagnosis of patients with this condition. PMID- 8201173 TI - Comparative metabolism of deltamethrin and 3-phenoxybenzoic acid in chickens. AB - A comparative metabolism of [benzyl 14C]deltamethrin and 3-phenoxybenzoic acid (3 PBacid) was carried out in chickens. The effect of oral and intravenous route of administration was also investigated. There was no difference in the metabolic profile of [14C] portion of deltamethrin and 3-PBacid. Similarly, no effect on the nature of metabolites excreted due to mode of administration was observed. Biotransformation of orally dosed compounds did not occur in the intestine, but were absorbed and metabolized by liver (deltamethrin) and kidney (3-PBacid). 3 PBacid, the primary metabolite of deltamethrin, was readily metabolized into 3 hydroxy benzoic acid (3-HO-Bacid) which is conjugated with a variety of endogenous substances to form sulphates, glucuronides, butyl ester and peptides. HPLC and LC-Ms methods were used to ascertain the structures of metabolites. PMID- 8201174 TI - Evaluation of commercial immunoassays for the detection of alachlor in milk, eggs and liver. AB - For regulatory purposes, there is a need for rapid, uncomplicated, and inexpensive methods to monitor pesticide residues in food. Commercial immunoassay kits from 3 manufacturers were evaluated for the detection of alachlor in cow milk and urine, and one kit was chosen for assay of chicken eggs and livers. Milk and urine were analyzed after a 1:2 dilution in water, and a rapid extraction procedure was developed for eggs and liver samples. Assays of incurred samples were performed after dosing a cow and several chickens with alachlor. Alachlor was detected in milk and eggs, but not in livers from hens dosed up to 12 mg/kg body weight. The ELISA detection limits were 0.3 ng/mL in milk, 2 ng/g in eggs, and 3 ng/g in liver. The major drawback with the kits was the low cross reactivity of the antibodies for some of the alachlor metabolites. PMID- 8201175 TI - The effect of multiple soil applications of disulfoton on enhanced microbial degradation in soil and subsequent uptake of insecticidal chemicals by potato plants. AB - Potatoes were grown during 1992 in 2 m2 plots of loam which had received 1, 2 or 3 annual treatments of Di-Syston 15G, equivalent to 3.36 kg AI/ha, in furrow at planting. The presence of enhanced degradative activity to the sulfoxide and sulfone metabolites of disulfoton in the soil treated in the previous two years was confirmed by laboratory tests prior to the 1992 treatments. Soil, seed potato and foliage from the three treatments were analyzed for disulfoton and its sulfoxide and sulfone metabolites for 12 wk following planting/treatment. Disulfoton was the major insecticidal component of the soil, a minor component of the seed piece and was not detected (< 0.02 ppm) in potato foliage. Disulfoton concentrations in each of the three substrates sampled were similar for the three treatments. Disulfoton sulfoxide and sulfone were the major insecticidal components of the seed piece and foliage. Their maximum concentrations in 1st year soil, seed pieces and foliage were ca. 2x, 2x and 6x, respectively, those measured in the 2nd and 3rd year treatments. The results demonstrate that enhanced microbial degradation of relatively minor insecticidal compounds in the soil can profoundly affect insecticide levels in the plant when these compounds are the major insecticidal components accumulated. The broader implications for crop protection using soil-applied systemic insecticides are discussed. PMID- 8201176 TI - Discovering the right questions--our call to action--who will define health care rationing, and how? AB - Will the citizens and legislators of our country be accurately informed in enough detail to decide wisely on the proposed health care plans? If we cannot afford all health care for all people, how can we make the government use the words "rationing health care" and be certain that the rationing is done by the stakeholders (patients and providers)? Changes in the health care system are needed and it must be improved, but does that justify totally changing a system providing the best care in the world for 200 million people? Or should we build on and improve that which is good and extend it to the remaining 10-15% who are currently without insurance? Can the government guarantee good health? Does this imply we are to guarantee health, then food, and then housing and clothing? Or, rather, should we guarantee the right to pursue a job that allows the purchase of health care insurance, just as we have the right to purchase housing, food, and clothing? Can we guarantee health to our citizens, or must we guarantee the right to pursue good health? How much should we spend on health care? Is the health care industry a growth industry with the product a healthier population? If so, should it be punished or encouraged? Is what we spend out of line with what is spent on entertainment, tobacco, and alcohol? When viewed from that perspective is health care too expensive or a bargain? Will the individual citizen accept his/her individual obligation to change habits and lifestyle? Do the people of this country really want a health care service with the regulatory simplicity of the tax law, the frugality of the Pentagon, the efficiency of the Post Office, and the compassion of the IRS? To be consistent with the Vice President's efforts to downsize government should government involvement in health care be increased or decreased? Are the proper innovations underway on the state level? Is federal law necessary now at all, or should Washington just monitor the emerging new programs at the regional and state levels? If England and Sweden are backing away from socialism and starting to privatize, and if major cities in our own country are acknowledging governmental failure and inability to deliver cost-effective quality service for such simple things as trash collection and maintenance of park systems, how can our federal government run health care?(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201177 TI - Arthrodesis of the proximal interphalangeal joint of the finger: comparison of the use of the Herbert screw with other fixation methods. AB - We report a retrospective review of 224 proximal interphalangeal joint arthrodeses in the digits using Herbert screws (37), Kirschner wires (100), tension band wiring (69), plates (11), and other miscellaneous techniques (7) for fixation. Average time to clinical union was 7 weeks and time to radiographic union was 10 weeks. Nonunion occurred in 31 cases (24 digits). The primary nonunion rate was highest in psoriatic arthritis, intermediate in rheumatoid arthritis, lower in acute trauma and post-traumatic reconstruction, and nonexistent in osteoarthritis. The primary nonunion rate was highest using Kirschner wires, intermediate using tension band wires, and lowest using Herbert screws. All Kirschner wires, six tension band wires and one Herbert screw were removed after fusion. The Herbert screw provides secure fixation, is easy to insert, and affords a rapid and reliable arthrodesis at the proximal interphalangeal joint. PMID- 8201178 TI - Fracture subluxation of proximal interphalangeal joint treated by palmar plate advancement. AB - A modified technique of palmar plate advancement (PPA) was used to treat certain patients, most with failed previous treatment, with fracture subluxation of the proximal interphalangeal joint. The modification of the original technique consisted of using two sutures to attach the palmar plate and tying them deep to the skin on the dorsum. This allowed consistent maintenance of reduction, and there were no infections. The results of 11 of 23 patients who were treated with this technique and followed from 2 to 9 years postoperatively are reported. The indications for PPA in this injury are discussed. PMID- 8201179 TI - Irreducible distal interphalangeal joint dislocation of the finger: a new cause. PMID- 8201180 TI - The palmar cutaneous branch of the median nerve and the palmaris longus tendon: a cadaveric study. AB - The purpose of this study was to determine the frequency with which the palmar cutaneous branch of the median nerve passes through the palmaris longus tendon. Fifty-two wrists (27 cadavers) were dissected. In three wrists the palmaris longus tendon was absent. The palmar cutaneous branch was seen to course through the fibers of the palmaris longus in two specimens (different cadavers). The nerve passed through the tendon 1 and 1.5 cm proximal to its insertion into the palmar aponeurosis. In the presence of this anomaly the palmar cutaneous branch of the median nerve is at risk of injury during harvesting of the palmaris longus tendon for grafts. To avoid injury, we recommend transecting the tendon 2 cm proximal to its insertion into the palmar aponeurosis. PMID- 8201181 TI - Implantation of the palmar cutaneous branch of the median nerve into the pronator quadratus for treatment of painful neuroma. AB - A neuroma of the palmar cutaneous branch (PCB) of the median nerve can cause pain in the scar following carpal tunnel release, with secondary decreased wrist range of motion and decreased grip strength. The results of PCB resection and implantation of the PCB into the pronator quadratus muscle are reported in a series of 13 patients. Pain relief was demonstrated before surgery by anesthetic block of the PCB, which did not result in sensory loss in the distribution of the median nerve. Results, at a mean of 19 months after surgery, were excellent (no residual pain, return to previous jobs) in six patients and good (some residual pain, return to a different job, stable or improved grip strength and wrist range of motion) in seven patients. PMID- 8201182 TI - Salvage of a below-elbow amputation stump with a free latissimus dorsi muscle flap: a case report. PMID- 8201183 TI - Development of a quantitative hand grasp and release test for patients with tetraplegia using a hand neuroprosthesis. AB - We developed a quantitative grasp and release test for assessing a hand neuroprosthesis in C5 and C6 level tetraplegic patients. The objectives were (1) to determine if a patient's hand performance with the neuroprosthesis exceeded a defined, clinically acceptable baseline, (2) to compare performance with and without the neuroprosthesis, (3) to measure the consistency of performance over time, and (4) to compare performance among patients. In the test, patients grasped, moved, and released one of six different objects as many times as possible in five 30-second trials for each object, with and without the neuroprosthesis. Unlike earlier tests, the objects and the task were chosen to span a range of difficulties appropriate for C5 and C6 tetraplegic patients using a hand neuroprosthesis. Data from five patients showed that performance with the neuroprosthesis was above the baseline; performance improved with the neuroprosthesis, although it was not generally consistent across sessions; and the neuroprosthesis helped C5 patients manipulate most objects and helped C6 patients primarily with more difficult objects. PMID- 8201184 TI - Long-term results of Kienbock's disease treated by triscaphe arthrodesis and excisional arthroplasty with a coiled palmaris longus tendon. AB - Fifteen patients with Kienbock's disease were treated with scaphotrapeziotrapezoidal arthrodesis and lunate excisional arthroplasty with a coiled palmaris longus tendon replacement. Patients were classified into five groups preoperatively according to Lichtman's classification: stage IIIA, 1 patient; stage IIIB, 11; and stage IV, 3. After an average follow-up period of 57 months, the clinical results were evaluated by the method described by Lichtman et al. Twelve patients were rated as satisfactory, and three patients were rated as unsatisfactory. Clinical results were good with regard to pain relief and grip strength, but poor with regard to range of motion of the wrist. Five patients revealed postoperative progression of osteoarthritic changes at the radioscaphoid joint, and this appeared to be a main factor influencing clinical results. Two of these five patients had subsequent wrist arthrodesis. We conclude that stage IIIB is a specific indication for scaphotrapeziotrapezoidal arthrodesis. PMID- 8201185 TI - Negative ulnar variance is not a risk factor for Kienbock's disease. AB - Ulnar variance was measured in standardized conditions in 125 normal wrists and in 52 patients with Kienbock's disease. No significant difference in ulnar variance between a sex/age-matched control group and a group of patients affected with Kienbock's disease was found. A positive correlation was found between age and ulnar variance. No significant difference was found between men and women. Based on these results, negative ulnar variance does not seem to be an important factor in the etiology of Kienbock's disease. PMID- 8201186 TI - Nerve transfer to biceps muscle using a part of ulnar nerve for C5-C6 avulsion of the brachial plexus: anatomical study and report of four cases. AB - Four patients with C5-C6 root avulsion after brachial plexus injury were treated with a transfer of part of a normal functioning nerve in the arm to the motor nerve of the biceps. Ten percent of the bulk of the ulnar nerve was harvested for a suture directly to the motor nerve of the biceps with no significant impairment of hand function. PMID- 8201187 TI - Use of intercostal nerves as nerve grafts in hand reconstruction with rectus abdominis flaps. PMID- 8201189 TI - Simultaneous rupture of both flexor tendons in a finger. PMID- 8201188 TI - The transverse radioulnar branch from the dorsal sensory ulnar nerve: its clinical and anatomical significance further defined. AB - The anatomy of the dorsal sensory ulnar nerve has been well described, but a transverse branch that innervates the distal radioulnar joint and overlying skin, has not been well delineated. This study, from both an anatomic and clinical perspective, confirms its presence approximately 80% of the time and documents the size, course, and type specificity. PMID- 8201190 TI - Cellular survival and proliferation in autogenous flexor tendon grafts. AB - In order to investigate fibroblast survival and proliferation in autogenous flexor tendon grafts, hindlimb intrasynovial and extrasynovial donor tendons were placed within the synovial sheaths of the medial and lateral forepaw digits of 21 dogs (42 tendons) and treated with controlled early passive motion. Intravital histologic evaluations with confocal microscopy and biochemical determinations of total DNA content and DNA synthesis were carried out at 10 days, 3 weeks, and 6 weeks. Intravital staining of the extrasynovial tendon grafts demonstrated variable degrees of cellular necrosis at the earliest intervals followed by cellular repopulation with fibroblasts and neovascularization from surface vessels. In contrast, intrasynovial tendon grafts were populated predominantly by viable cells at each interval, with occasional patches of cell necrosis and fibroblast ingrowth. Total DNA content and DNA synthesis values in the intrasynovial donor tendons were significantly lower than those seen in the extrasynovial tendon grafts at each interval. Extrasynovial tendons appear to act as scaffolds, undergoing extensive cellular death followed by a rapid repair response. Findings that intrasynovial tendon fibroblasts survive the tendon grafting process suggest that the nutritional supplies and metabolic requirements of intrasynovial and extrasynovial donor tendons differ largely. PMID- 8201192 TI - Calcific tendinitis at the biceps insertion causing rotatory limitation of the forearm: a case report. PMID- 8201191 TI - Variations in cellular proliferation and matrix synthesis in intrasynovial and extrasynovial tendons: an in vitro study in dogs. AB - Intrasynovial and extrasynovial flexor tendon grafts recently have been shown to have dissimilar patterns of cellular survival and host integration within the digital sheath. In an effort to determine if fundamental differences exist between these two types of tendons, we investigated the biochemical composition and cellular activity of intrasynovial and extrasynovial tendon segments of 12 adult mongrel dogs in short-term explant culture in MCDB 105 and in DMEM media. Proteoglycan, collagen and noncollagen protein synthesis and content and DNA synthesis were determined following culture in both media. Intrasynovial tendon segments cultured in MCDB 105 medium synthesized significantly less collagen, noncollagen protein, and DNA and had similar amounts of proteoglycans compared to extrasynovial tendons. Comparison of intrasynovial and extrasynovial tendon segment responses in DMEM medium showed that intrasynovial tendons synthesized more proteoglycan, protein, and DNA than they did in MCDB 105. Extrasynovial tendons had similar rates of matrix component and DNA synthesis in both media. Findings that the synthesis of matrix components and DNA between intrasynovial flexor and extrasynovial peroneal tendon segments differ significantly indicate that intrasynovial flexor tendons may be specially adapted to the nutritional milieu provided by an intrasynovial environment. These data are supported by the selective successful stimulation of fibrocartilaginous segments within intrasynovial flexor tendons in media favored for the culture of cartilaginous tissue. PMID- 8201193 TI - Physiologic consequences of surgical lengthening of extensor carpi radialis brevis muscle-tendon junction for tennis elbow. AB - Sarcomere length was measured intraoperatively using a laser diffraction method before and after surgical lengthening of the human extensor carpi radialis brevis muscle (ECRB) in five subjects treated for lateral epicondylitis. Based on measured sarcomere and filament lengths, we previously established the length tension curve for this muscle and the normal sarcomere length range as a function of wrist joint angle. Preoperative measurements indicated that the ECRB developed near-maximal isometric force at full wrist extension, decreasing to 20% maximum at full wrist flexion. Stair-step surgical tendon lengthening of the ECRB by 9.1 mm resulted in mean ECRB sarcomere shortening of 0.30 microns. This 0.30 microns shortening was predicted to have two primary biomechanical effects: (1) a 25% decrease in muscle passive tension that could lead to reduced insertional tension and decreased pain and (2) a 25% increase in active muscle force that opposes the notion that tendon lengthening necessarily results in muscle weakness. PMID- 8201194 TI - Flexor digitorum superficialis lasso tendon transfer in isolated ulnar nerve palsy: a functional evaluation. AB - Twelve patients (23 digits) with isolated ulnar nerve palsy underwent flexor digitorum superficialis lasso tendon transfers for correction of claw deformity, weakness, and asynchronous digital flexion. The average follow-up period from date of injury was 5 years (range, 2-11 years) and from surgery was 3 years (range, 15 months to 7 years). Transfers successfully corrected the claw deformity in 19 of the 23 digits. Three of the four failures occurred in the small finger. Two of the four failures had uncorrected preoperative proximal interphalangeal joint flexion contractures. In 9 of the 12 patients with pre- and postoperative grip strength measurements no significant improvement in grip strength was noted. While this procedure is effective and predictable in correcting deformity and restoring synchronous pattern of finger flexion, it should be used with caution in patients requiring an increase in grip strength. PMID- 8201196 TI - Osteosarcoma of the hand: a case report and review of the literature. PMID- 8201195 TI - Vascular leiomyomas in the hand. AB - Vascular leiomyomas or angioleiomyomas are benign solitary smooth muscle tumors that occur uncommonly in the hand. The peak incidence is in the third to fifth decades of life, and men are more often affected than women. This tumor is rarely diagnosed before surgery. The usual treatment is simple excision of the mass and ligation of feeder vessels. Although the tumors occur anywhere in the hand, there are only two previous cases of vascular leiomyoma involving the digital artery. A recent case of this tumor involving a digital artery documented by arteriography and treated by excision of the mass and end-to-end anastomosis of the artery is presented. The authors review their experience with vascular leiomyomas in the hand and present four cases along with a review of 105 cases found in the English literature. PMID- 8201197 TI - Fibroosseous pseudotumor of the digit: report of a case. PMID- 8201198 TI - Candida tenosynovitis in an AIDS patient: a case report. PMID- 8201199 TI - Magnetic resonance imaging of the anterior radiocarpal ligaments. AB - Magnetic resonance imaging was applied to eight cadaver wrists to evaluate the efficacy of imaging the anterior radiocarpal ligaments. In order to verify a correlation between the magnetic resonance images and anatomic structures, ancillary studies using gadolinium-DTPA ligamentography and gross sectioning of the specimens were performed. The ligaments targeted for evaluation were the radioscaphocapitate, long radiolunate, and short radiolunate ligaments. The highest resolution images were obtained using a 1.5 Tesla magnetic resonance imaging scanner and a surface coil applied to the wrist region, and producing T1 weighted images, with 3 mm thick sections with an 8 cm field of view. The radioscaphocapitate, long radiolunate, and short radiolunate ligaments were most consistently identified in sagittal planes, however they were also identified in coronal planes. The radioscapholunate ligament and the interosseous ligaments between the scaphoid, lunate, and triquetrum were most consistently identified in coronal planes. Transaxial planes provided consistently inferior views, and should be reserved for imaging of the flexor and extensor retinaculae. PMID- 8201200 TI - Ultrasonographic detection of thumb ulnar collateral ligament injuries: a cadaveric study. AB - Ten fresh-frozen cadaveric thumbs were utilized to determine whether ultrasound is a useful tool for diagnosing ruptures of the ulnar collateral ligament. The integrity of the ulnar collateral ligament was evaluated by ultrasound and confirmed by dissection. Partial ruptures were produced by gentle manual loading in four of the cases and were all correctly diagnosed by ultrasound. Six complete ruptures occurred secondary to forceful loading and were diagnosed as torn in five of them. Ultrasound correctly determined the presence of an iatrogenic Stener's lesion in one specimen and an intra-articular displacement in another. In the laboratory setting, repeated clinical stress examinations of the ulnar collateral ligament can lead to iatrogenic displacement of the ligament edges. Diagnostic ultrasound is a useful, noninvasive tool for assessing the extent of rupture of the ulnar collateral ligament. PMID- 8201201 TI - Incidence of ligament lesions and associated degenerative changes in the elderly wrist. AB - The scapholunate, lunotriquetral, and triangular fibrocartilage of 62 cadaveric wrists were examined to determine the incidence of pathologic changes in asymptomatic elderly wrists. A scapholunate ligament lesion was noted in 18 wrists; the majority of defects were incomplete and involved the central portion of the ligament only. Lunotriquetral ligament defects were noted in 20 wrists; eight were partial defects, most of them were central ligament lesions. Triangular fibrocartilage defects were present in 33 wrists and consisted of two distinct patterns: a central oval pattern with actual tissue loss and a linear defect running in the dorsal anterior direction 2-3 mm ulnar to the radial attachment of the triangular fibrocartilage. X-ray film evaluation showed few significant degenerative changes with no pronounced collapse deformities. Defects involving the scapholunate, lunotriquetral, or triangular fibrocartilage were very common, with the presence of at least one of these ligament defects in wrists. These ligament defects occur as a process of aging and behave in a manner quite different from traumatic lesions of these same structures in the younger population. PMID- 8201202 TI - Isoelastic arthroplasty of the metacarpophalangeal joints in rheumatoid arthritis: a preliminary report. AB - The Isoelastic prosthesis for the metacarpophalangeal joint was used in 68 rheumatoid joints. The average follow-up period was 3 years and 3 months. The subjective score for pain, appearance, and usefulness as well as the functional outcome was determined by means of a modified Green test. All subjective scores improved postoperatively, whereas function did not change significantly. Preoperative range of motion values were not available. The extension deficit after operation was 26 degrees, the average flexion 63 degrees, and the total range of motion 37 degrees. Grip strength improved only slightly. Complications included four cases of delayed wound healing and four metacarpal fractures after operation. The Isoelastic prosthesis gives satisfactory results in rheumatoid arthritis patients. The intraoperative insertion is easy and the material is well tolerated. In vivo, the implant itself is rigid enough to resist ulnar drift, although osteolysis around the plastic surface has caused recurrence of ulnar deformity. PMID- 8201203 TI - Factors affecting functional outcome of displaced intra-articular distal radius fractures. AB - Open reduction and internal fixation is often required in comminuted, displaced intra-articular fractures of the distal radius when closed manipulation has failed to restore articular congruity. Results of surgical stabilization and articular reconstruction of these injuries are reviewed in this retrospective study of 49 patients with 52 displaced, intra-articular distal radius fractures. Forty-three patients with a mean age of 37 years (range, 17-79 years) were available for evaluation. The mean follow-up time was 38 months (range, 22-69 months). When rated by the system proposed by the Association for the Study of Internal Fixation (ASIF), 19 were ASIF type C2 and 21 were ASIF type C3. An injury score system based on the initial injury x-ray films was used to classify severely comminuted intra-articular fractures and to identify those associated with carpal injury. Postoperative fracture alignment, articular congruity, and radial length were significantly improved following surgery. Grip strength averaged 69 +/- 22% of the contralateral side, and range of motion averaged 75 +/ 18% of the contralateral side after surgery. A combined outcome rating system that included grip strength, range of motion, and pain relief averaged 76 +/- 19% of the contralateral side. Using regression analysis, a significant decrease was found in the combined rating with more severe fracture patterns as defined by the ASIF system, Malone classification, and the injury score system. The injury score system presented here and, in particular, the number of fracture fragments correlated most closely with the outcome of all classification systems examined. Operative treatment of complex distal radius fractures with reconstruction of articular congruity with internal fixation and/or external fixation can significantly improve functional outcome. The degree to which articular step-off, gap between fragments, and radial shortening are improved by surgery is strongly correlated with improved outcome, even when the results are corrected for severity of initial injury, whereas correction of radial tilt or dorsal tilt did not correlate with improved outcome. PMID- 8201204 TI - The scaphoid shift test. PMID- 8201205 TI - The wrist tourniquet: an alternative technique in hand surgery. PMID- 8201206 TI - A reversed digital artery island flap for the treatment of fingertip injuries. PMID- 8201207 TI - Acute calcific tendinitis in children. PMID- 8201208 TI - Effect of large-volume paracentesis on pulmonary function in patients with cirrhosis and tense ascites. AB - The effect of large-volume paracentesis on lung function was evaluated in 12 male patients with cirrhosis. All underwent pulmonary function tests including spirometry, plethysmography and single-breath carbon-monoxide diffusing capacity 1 day before and after paracentesis. The amount of ascitic fluid removed ranged from 3.6 to 131 (mean +/- SD, 7.4 +/- 3.01). After paracentesis, forced vital capacity, forced expiratory volume at 1 s, total lung capacity, functional residual capacity, inspiratory capacity, expiratory reserve volume, diffusing capacity and alveolar volume increased significantly. In contrast, Kco (diffusing capacity corrected by alveolar volume) decreased significantly. After paracentesis, the increase in diffusing capacity was highly correlated with lung volumes and the amount of removed ascitic fluid. Nevertheless, a significantly negative correlation was found between the change of Kco before and after paracentesis and that of lung volumes. The increase in lung volumes and ventilation to the lower lungs with unfavorable ventilation-perfusion matching might explain the discrepancy between changes in diffusing capacity and Kco after large-volume paracentesis. In conclusion, these results suggest that pulmonary function in patients with cirrhosis and tense ascites is partly improved by large volume paracentesis. Large-volume paracentesis might be useful for symptomatic relief in selected patients with tense ascites. PMID- 8201209 TI - Plasma hepatocyte growth factor and biliprotein levels and outcome in fulminant hepatic failure. AB - Plasma levels of growth factors may be important in determining the extent of liver regeneration in patients with fulminant hepatic failure and in this study human hepatocyte growth factor and biliprotein (bilirubin covalently bound to albumin) were determined in patients with fulminant hepatic failure, mainly as a result of acetaminophen overdose. Admission values for plasma human hepatocyte growth factor were significantly raised, although with a wide range in acetaminophen-induced fulminant hepatic failure (median 7.4 ng/ml, range 0.45 48.4 ng/ml, n = 34) and in fulminant hepatic failure from other causes (3.8 ng/ml, 1.72-25.1 ng/ml, n = 9) as compared to normal subjects (0.24 ng/ml, 0-0.5 ng/ml, n = 30). Higher plasma human hepatocyte growth factor was observed in patients who died (10.1 ng/ml, 3.8-48.4 ng/ml, n = 19) than in those who survived (4.3 ng/ml, 0.45-25.1 ng/ml, n = 22, p < 0.02), which may reflect lack of hepatic clearance in the former group. The median plasma biliprotein on admission (13.2 mg/l, range 6.3-100.7 mg/l, n = 43) was significantly increased compared to normal subjects (1.3 mg/l, 0-4.1 mg/l, n = 7, p < 0.001) with no difference between patients who survived or died, although when plasma biliprotein results were expressed as a percentage of the total bilirubin, the values were slightly higher in survivors (median 14.4%, range 10.8-40.5%, n = 23) compared to those who died (12.1%, 7.7-20.9%, n = 20, p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201210 TI - The relationship of endoscopy, portal Doppler ultrasound flowmetry, and clinical and biochemical tests in cirrhosis. AB - The relationship of the endoscopic aspect of esophageal varices, portal quantitative Doppler ultrasound parameters and clinical and biochemical findings was assessed in 149 patients with cirrhosis stratified according to the presence of esophageal varices (n = 115) and the absence of previous bleeding (n = 96). In this series of patients the presence of esophageal varices and red signs proved to be significantly correlated with the severity of cirrhosis. However, in the group of patients with varices, no correlation was found between variceal size and the degree of liver failure. Portal blood flow velocity was significantly different in the endoscopic subgroups, but not in the clinical and biochemical subgroups. Furthermore, portal blood flow velocity was found to correlate only with the presence and size of esophageal varices. The Congestion Index of the portal vein (derived from the ratio between the cross-sectional area of the portal vein and the mean velocity of portal flow) was significantly different in most clinical, biochemical and endoscopic subgroups and was correlated with liver function, presence and size of varices, and presence and degree of red signs. We conclude that the Congestion Index of the portal vein, the clinical status and the endoscopic aspect of varices are not independent features in patients with cirrhosis. As for liver function and endoscopic findings, portal Doppler ultrasound parameters, in particular the Congestion Index, may contribute to a better clinical assessment in patients with cirrhosis. PMID- 8201211 TI - Antibiotic-associated acute vanishing bile duct syndrome: a pattern associated with severe, prolonged, intrahepatic cholestasis. AB - We report cases of amoxycillin- and flucloxacillin-induced liver damage associated with an acute vanishing bile duct syndrome. Ductopenia was present at the time of first liver biopsy, 3 weeks and 3 months after administration of the two drugs, respectively. Ductopenia apparently occurred as the primary lesion, with no evidence of accompanying portal tract inflammation. Subsequent biopsies showed a persistent paucity of ducts, accompanied by increasing features of chronic cholestasis. Biochemical dysfunction persists at 2 year's follow-up and late prognosis remains guarded. PMID- 8201212 TI - The evaluation of fine-needle procedures for the diagnosis of focal liver lesions in cirrhosis. AB - To evaluate the diagnostic accuracy of fine-needle aspiration, fine-needle biopsy and extranodular fine needle biopsy in identifying focal lesions in cirrhosis, 100 consecutive ultrasound detected nodules were studied. Seventy-three were hepatocellular carcinomas (31 were well-differentiated hepatocellular carcinomas), 23 were benign lesions (one angioma and 22 large regenerative nodules) and two were metastases. The lesions were divided according to maximum diameter as follows: < 20 mm in 36, > 20 < 30 mm in 27, and > 30 mm in 33. In four cases there were multiple nodules of different sizes. Fine needle aspiration, intranodular fine needle biopsy and extranodular fine needle biopsy were obtained in each lesion. The sensitivity, specificity and diagnostic accuracy of each procedure were evaluated separately by three independent pathologists. Seven fine needle aspirations and three intranodular fine needle biopsies were considered inadequate. The highest diagnostic accuracy (96%) was obtained by the combined analysis of fine needle aspiration plus intranodular and extranodular fine needle biopsy, and this superiority was confirmed in each group of lesions. Fine needle aspiration showed a lower accuracy (48%) than intranodular fine needle biopsy (67%). When fine needle aspiration and intranodular fine needle biopsy were evaluated together, an accuracy of 91% was found. Intralesional fine needle biopsy plus extranodular fine needle biopsy analysis gave an accuracy of 78% and, particularly relevant, a specificity of 95%. These results indicate that, in patients with cirrhosis with nodular lesions < 30 mm, fine needle biopsy is superior to fine needle aspiration and that the combined evaluation of fine needle aspiration plus intranodular and extranodular fine needle biopsy is the most accurate approach.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201214 TI - Laparoscopic study of peliosis hepatis and nodular transformation of the liver before and after renal transplantation: natural history and aetiology in follow up cases. AB - Although peliosis hepatis and nodular transformation of the liver can occur after renal transplantation, their prevalence has not been well defined. To investigate the incidence of these complications, 137 laparoscopies were studied, 52 in 50 cases before and 85 in 66 cases after renal transplantation. To elucidate the aetiology and natural history of these diseases, cases were followed up by repeated laparoscopies. Peliosis was observed after transplantation (before: n = 1, after: n = 15 [22%], p < 0.005). Nodular transformation was seen only after transplantation (n = 5 [7%]), and was accompanied by peliosis (n = 4, p < 0.01). On observation before and after transplantation in the same cases, these diseases appeared after transplantation (peliosis: n = 9, p < 0.005; nodular transformation: n = 2). In follow-up cases, these diseases were confirmed after the discontinuation of or the controlled administration of immunosuppressants. The aetiology of the micronodular transformation which appeared following peliosis in a case treated without cyclosporin was shown to be azathioprine. However, the macronodular transformation observed in two cases treated with both azathioprine and cyclosporin seemed to be due to cyclosporin. This suggests that cases of peliosis hepatis and nodular transformation which appear after renal transplantation are associated with immunosuppressants, and that cyclosporin treatment may also affect the morphogenesis of nodular transformation. PMID- 8201213 TI - Regulation of tumor necrosis factor-alpha-mRNA synthesis and distribution of tumor necrosis factor-alpha-mRNA synthesizing cells in rat liver during experimental endotoxemia. AB - Stimulated liver macrophages (Kupffer cells) are known to release a variety of inflammation-related substances, e.g. cytokines, prostanoids, and reactive oxygen intermediates. For instance, exposure of Kupffer cells in vitro to lipopolysaccharide (endotoxin) leads to a strongly enhanced synthesis of the mRNA for tumor necrosis factor-alpha, the release of the mature protein into culture media. These events are influenced by prostanoids and corticoid hormones. Kupffer cells are thought to be the only source of tumor necrosis factor-alpha within the hepatic sinusoid, but neither this cell specificity nor the regulatory influence of glucocorticoids or prostanoids has been confirmed in the intact organ. Using non-radioactive in situ hybridization, it was possible to obtain specific signals for tumor necrosis factor-alpha-mRNA in individual Kupffer cells uniformly distributed (as compared to Kupffer cells detected by immunohistochemistry) throughout the liver. Kupffer cells were the only cells in the hepatic sinusoids of lipopolysaccharide-perfused livers to express mRNA for tumor necrosis factor alpha. Simultaneous addition of endotoxin plus dexamethasone and endotoxin and prostaglandin E2 completely suppressed the synthesis of this mRNA. Unexpectedly, the presence of mRNA for tumor necrosis factor-alpha was also detected in the intrahepatic bile duct epithelium of lipopolysaccharide-perfused livers. It is known that biologically active endotoxin is secreted via the bile ducts. These results seem to indicate that bile duct epithelium responds to inflammatory agents with synthesis of tumor necrosis factor-alpha-mRNA. One must also consider new functional aspects of bile duct epithelium in chronic inflammatory diseases, e.g. primary biliary cirrhosis, chronic sclerosing cholangitis or graft-versus host disease. PMID- 8201215 TI - Nicotinamide methylation in patients with cirrhosis. AB - Methylation reactions play an important role in the transformation of endogenous and exogenous substances. Up to 85% of all transmethylation reactions occur in the liver. Several studies have shown that these metabolic processes are greatly influenced by the presence of hepatic diseases. We investigated the methylation of nicotinamide in 16 control subjects and in 29 patients with cirrhosis (19 Child A, 10 Child B). The basal serum value of N-methyl-nicotinamide was measured in all subjects. In seven controls and in nine patients with cirrhosis (5 Child A and 4 Child B), the serum levels and urinary excretion (5 and 24 h) of N-methyl nicotinamide were also evaluated after oral administration of nicotinamide (1.5 mg/kg body weight). The basal serum levels of N-methyl-nicotinamide were significantly (p < 0.05) higher in patients with cirrhosis (Child A: median 34 ng/ml, 16th percentile 24, 84th percentile 61; Child B median 45, 16th percentile 34, 84th percentile 81) than in controls (median 22, 16th percentile 13, 85th percentile 28). After the nicotinamide load the urinary excretion and the time course of serum N-methyl-nicotinamide in cirrhosis were also higher (p < 0.05) than in controls (24 h urinary excretion = 66.2 mg +/- 5 S.D. in cirrhosis; 47.2 +/- 10.3 in controls) (area under the serum concentration versus time curve = 68 micrograms.ml-1.min-1 +/- 22 S.D. in cirrhosis; 32 +/- 15 in controls). In conclusion, our results show that cirrhosis does not impair the efficiency of nicotinamide methylation. PMID- 8201216 TI - Persistence of "wild-type" and "e-minus" hepatitis B virus infection in chronic healthy HBsAg/anti-HBe positive carriers. AB - We examined nine chronic healthy hepatitis B surface antigen/antibody to hepatitis Be carriers with consistently normal liver chemistries and negative serum hepatitis B virus-DNA. Liver biopsy, performed twice, 10-11 years apart in all patients, showed normal histology and negative hepatitis B core antigen. DNA extracted from the second liver biopsy specimen, from 1 ml of serum from each patient and from an additional serum sample of 6 ml from two patients, was tested for pre-C/C and pre-S regions of hepatitis B virus-DNA by polymerase chain reaction amplification. Viral sequences were found in six of nine liver DNA extracts. In four cases both pre-C/C and pre-S regions were amplified, while the pre-C/C alone and the pre-S alone were detected in one case each. Direct sequencing of the amplified DNAs revealed no significant genomic changes in the pre-S and Core regions, while analysis of the pre-Core demonstrated the presence of a double viral population (wild-type and "e-defective") in four cases, and only "e-defective" hepatitis B virus in one case. No hepatitis B virus genomes were revealed in the serum sample when DNA was extracted from 1 ml of serum, while viral sequences were detected in both extracts of 6 ml of serum, indicating the presence of very low levels of viremia. These data suggest that episomal hepatitis B virus-DNA may persist for years in the liver of chronic healthy carriers in a latent state which may involve both wild-type and HBeAg-defective hepatitis B virus. PMID- 8201217 TI - Detection of hepatitis C virus RNA by "hot start" polymerase chain reaction. PMID- 8201218 TI - Intravascular hemolysis and transjugular intrahepatic portosystemic stent shunt. PMID- 8201219 TI - Immunoprophylaxis with hepatitis B immunoglobulin after liver transplantation: an economical approach. PMID- 8201220 TI - The submicrosomal localization of uridine 5'-diphosphate-glucose dolichyl phosphate glucosyltransferase and bile acid glucosyltransferase in the human liver. AB - Uridine 5'-diphosphate-glucose dolichyl-phosphate glucosyltransferase and bile acid glucosyltransferase were quantitatively determined in subcellular fractions obtained by differential centrifugation of human liver homogenate. Both enzymes were exclusively enriched in the microsomal fraction with a recovery of total enzyme activity of 65.9 +/- 9.9% and 69.1 +/- 13.8%, respectively. Microsomal preparations were further subfractionated by isopycnic centrifugation on a continuous sucrose density gradient. Both glucosyltransferases closely followed marker constituents of endoplasmic reticulum, as shown by similar distribution profiles in the gradient, but differed in their quantitative distribution among the endoplasmic reticulum membranes. The bile acid glucosyltransferase showed an almost identical distribution with NADPH-cytochrome c reductase as marker of smooth endoplasmic reticulum with a modal density of 1.16 g/cm3. The uridine 5' diphosphate-glucose dolichyl-phosphate glucosyltransferase equilibrated at a higher density with a peak at a model density of 1.174 g/cm3. Its marked overlap with the distribution of NADPH-cytochrome c reductase suggests that the major activity of uridine 5'-diphosphate-glucose dolichyl-phosphate glucosyltransferase is also associated with smooth endoplasmic reticulum membranes, whereas minor proportions of enzyme activity are present in the rough endoplasmic reticulum. Association of both glucosyltransferases with membranes derived from Golgi complex or plasma membranes could be excluded by treatment of microsomes with membrane reagents prior to isopycnic centrifugation. Digitonin did not alter the equilibrium densities of the glucosyltransferases and endoplasmic reticulum markers in contrast to markers of plasma membranes and the Golgi-complex shifting to higher densities. The reversed effect was observed in case of pretreatment of microsomes with pyrophosphate known to detach ribosomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201221 TI - Low vitamin E content in plasma of patients with alcoholic liver disease, hemochromatosis and Wilson's disease. AB - The RRR-alpha-tocopherol (vitamin E) content in plasma from 46 patients with liver diseases and 23 healthy controls was determined by high performance liquid chromatography and electrochemical detection. Patients were divided into three groups: alcoholic liver diseases (n = 17; group A), hemochromatosis (n = 17; group B) and Wilson's disease (n = 12; group C). Lipid-standardized alpha tocopherol levels were determined to neutralize differences due to hyperlipemia. The ratio of serum vitamin E to serum lipids (cholesterol, triglycerides, phospholipids) was highest in healthy controls and in patients in group A with cirrhosis and normal transaminases and bilirubin. Patients in group A with acute or chronic ethanol intoxication and high bilirubin levels had a 37% lower lipid standardized vitamin E level than controls. Patients in group B with hemochromatosis, showing high serum iron (> 180 micrograms/dl), a low free iron binding capacity (< 8 mumol/l) and high ferritin-levels (< 450 micrograms/l), had a 34% lower vitamin E/lipid ratio than healthy controls. No significant lowering of the vitamin E/lipid ratio was observed in the other patients in group B. A significant decrease (37%) in the vitamin E/lipid ratio was only detectable in patients with Wilson's disease (group C) showing high free serum copper (> 10 micrograms/dl). The data support a role for free radicals in the pathogenesis of active liver diseases. PMID- 8201222 TI - PreS1 antigen/antibody patterns following interferon therapy in acute and chronic hepatitis B. AB - The relation between preS1 antigen/antibody system and different phases of hepatitis B virus infection were studied in 425 serum samples from 50 hepatitis B patients before, during and after antiviral therapy using interferon alone or in combination with corticosteroid withdrawal. A typical profile of self-limited acute hepatitis B was characterized by hepatitis B virus-DNA clearance using polymerase chain reaction and preS antigens using monoclonal radioimmunoassays and by antibody responses to the middle and the large HBs proteins (gp33/gp36 and p39/gp42) using immunoblotting quantitative analysis. After interferon therapy in patients with protracted hepatitis B, complete eradication of the virus was observed in 70% of patients, and antibody response directed to middle HBs and large HBs proteins could be induced. Conversely, this antibody response was never detected in follow-up studies of chronic active hepatitis B patients who responded well to antiviral therapy and lost HBs, preS2 and preS1 antigens. Most interesting, in 50% of patients with HBeAg-positive chronic active hepatitis B who received combination therapy and in 67% of patients with anti-HBe-positive chronic active hepatitis B given interferon alone, the elevated serum preS1Ag/HBsAg ratio persisted after treatment was discontinued and even increased until the end of the follow-up when hepatitis B virus DNA was undetectable in serum by the conventional hybridization technique. This rebound of preS1 antigen expression following antiviral therapy in patients with chronic active hepatitis B may indicate virus persistence, suggesting the possibility of relapse through wild-type hepatitis B virus or the emergence of hepatitis B virus mutants. PMID- 8201223 TI - The effect of propranolol on portal perfusion in patients with alcoholic cirrhosis having distal splenorenal shunt. AB - This study tested the hypothesis that reduction in the hyperdynamic systemic circulation with propranolol in patients with alcoholic cirrhosis and distal splenorenal shunt would lead to improved maintenance of portal perfusion. After standard distal splenorenal shunt, 50-75% of patients with alcoholic cirrhosis lose portal flow in 6-12 months: this is associated with an increased hyperdynamic systemic circulation. Twelve patients with alcoholic cirrhosis with distal splenorenal shunt received propranolol in a dose sufficient to provide beta blockade. Pulse was reduced by 25%, cardiac output reduced by 32% and hepatic venous pressure gradient reduced by 15% (p < 0.05). These significant hemodynamic changes with propranolol did not lead to any improvement in the maintenance of portal perfusion: overall, 66% of patients lost prograde portal flow within 1 year. We conclude that the hyperdynamic systemic circulation is not the primary mediator of loss of portal perfusion in this group of patients. Rather, it appears that differences in either intrahepatic resistance or collateral pathway (portal vein to shunt) resistance must account for the different patterns or maintenance of portal perfusion after distal splenorenal shunt. PMID- 8201224 TI - Effect of ursodeoxycholic acid on liver and bile duct disease in primary sclerosing cholangitis. A 3-year pilot study with a placebo-controlled study period. AB - Primary sclerosing cholangitis is a cholestatic disease of the liver characterized by progressive fibrotic inflammation and obliteration of the extra- and/or intrahepatic bile ducts. There is no effective therapy. We, therefore, studied the safety and efficacy of ursodeoxycholic acid in patients with primary sclerosing cholangitis with or without additional ulcerative colitis. In a 1-year ursodeoxycholic acid treatment period, which preceded the controlled study period, ursodeoxycholic acid was well tolerated in 22 of 24 patients with ulcerative colitis and in all three patients without ulcerative colitis. In two patients with ulcerative colitis the dose of 750 mg ursodeoxycholic acid/day led to diarrhea, but following reduction of the dose to 500 and 250 mg/day ursodeoxycholic acid was well tolerated. After 1 year of ursodeoxycholic acid treatment, 20 patients were randomly assigned to receive either ursodeoxycholic acid 750 mg/day or placebo. All of them finished a double-blind, placebo controlled study period. During ursodeoxycholic acid treatment, the liver enzymes improved markedly. The difference in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyltransferase between the placebo and ursodeoxycholic acid group was significant (p < 0.05). Following ursodeoxycholic acid treatment, pruritus and fatigue improved in half of the patients but the difference between the placebo and ursodeoxycholic acid group was not significant. According to the ethical guidelines, after 3 months of placebo treatment, the controlled study had to be discontinued because of a more than twofold increase of serum transaminases in 8/10 patients on placebo. After the end of the controlled study, all patients were continuously treated with ursodeoxycholic acid for up to 4 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201225 TI - Liver transplantation for end-stage liver disease associated with alpha-1 antitrypsin deficiency in children: pretransplant natural history, timing and results of transplantation. AB - Alpha-1-antitrypsin deficiency is an inborn metabolism error which can cause emphysema and liver disease. As regards the pathophysiology of liver disease, this deficiency is poorly understood, and it is also not known why only a small proportion of Pi ZZ individuals progress towards cirrhosis and liver failure. Since there is no specific therapy for end-stage liver disease associated with alpha-1-antitrypsin deficiency, patients are considered candidates for liver transplantation. In this paper, the natural history of 16 children who underwent liver transplantation is reviewed. Fourteen patients had neonatal cholestasis as a first symptom of the disease and hepatosplenomegaly was present in all children by the age of 12 months. In 11 children, jaundice recurred, always with liver function deterioration. Two patients had a histological paucity of interlobular bile ducts and required early transplantation due to rapid progression of liver failure. At the time of pretransplant assessment, all the patients in this study had portal hypertension and seven of them had experienced at least one episode of gastrointestinal bleeding. One child had moderate intrapulmonary shunts with hypoxemia, but the others had normal spirometry and blood gases. There was no other extrahepatic complication of alpha-1-antitrypsin deficiency. Eighteen orthotopic liver transplantations were performed in 16 patients. One patient died 8 days after retransplantation due to graft necrosis. Fifteen patients (94%) were alive after a median follow-up of 22 months with an excellent quality of life, normal serum alpha-1-antitrypsin levels and without evidence of liver disease recurrence or pulmonary complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201226 TI - Malignancy-related ascites: a diagnostic pitfall of spontaneous bacterial peritonitis by ascitic fluid polymorphonuclear cell count. AB - To define patients with an ascitic fluid polymorphonuclear cell count > or = 250 cells/mm3 or > or = 500 cells/mm3 but without spontaneous bacterial peritonitis, 166 patients with sterile cirrhotic ascites, 46 patients with spontaneous bacterial peritonitis, 123 patients with hepatocellular carcinoma, 67 patients with peritoneal carcinomatosis or massive liver metastasis and 12 patients with other miscellaneous diseases were studied. The sensitivity, specificity and accuracy of the diagnosis of spontaneous bacterial peritonitis were 100, 86 and 88% with the cut-off value of an ascitic fluid polymorphonuclear cell count > or = 250 cells/mm3; and were 93, 91 and 92% with that value > or = 500 cells/mm3, respectively. With the cut-off value > or = 250 cells/mm3 or > or = 500 cells/mm3, the prevalence was 18% or 14% in hepatocellular carcinoma; and 30% or 19% in peritoneal carcinomatosis or massive liver metastasis. The ascitic fluid lactate concentration was insensitive and nonspecific. Among the patients with an ascitic fluid polymorphonuclear cell count greater than the cut-off values, an ascitic fluid erythrocyte count > or = 10,000 cells/mm3, a ratio of ascitic fluid erythrocyte to total leukocyte count > or = 100, and the ratio of ascitic fluid polymorphonuclear cell to total leukocyte count < or = 75% indicated hepatocellular carcinoma, while serum to ascites albumin gradient < or = 1.1 g/dl and a ratio of ascitic fluid polymorphonuclear cell to total leukocyte count < or = 75% indicated peritoneal carcinomatosis or massive liver metastasis. PMID- 8201227 TI - Cholestasis in the male rat is associated with naloxone-reversible antinociception. AB - Clinical observations have suggested that cholestasis is associated with increased neurotransmission mediated by the opioid system in the central nervous system. As opiate agonists (e.g. morphine) mediate analgesia, increased opioidergic tone in cholestasis should be associated with a decreased response to pain. To test this hypothesis, the response of rats with acute cholestasis to a nociceptive stimulus was measured by the use of the tail-flick test, an extensively validated assay for measuring opiate-induced antinociception. Five and 7 days after bile-duct resection, the mean tail-flick latency was longer than before surgery (p < 0.05), whereas the corresponding means for unoperated and sham-resected controls were not significantly different from their respective baseline values. The increase in the mean tail-flick latency in the bile-duct resection group was reversed by (-)-naloxone (1 mg/kg subcutaneously), but not by its enantiomer (+)-naloxone (10 mg/kg subcutaneously) (p < 0.001). The stereoselective reversal of antinociception in cholestasis by naloxone indicates that this phenomenon is opioid-receptor mediated. In contrast, prolongation of the mean TFL found in the rat model of thioacetamide-induced acute hepatocellular necrosis was not reversed by (-)-naloxone, indicating that antinociception in this model is not opioid mediated. These findings provide support for the hypothesis that cholestasis is associated with increased opioidergic tone. PMID- 8201229 TI - No reinnervation of hepatic sympathetic nerves after liver transplantation in human subjects. AB - Transplantation of the liver results in surgical denervation of the organ. However, it is not known whether and to what extent sympathetic reinnervation occurs postoperatively in the transplanted human liver. Thirty-two liver biopsies (right lobe) were obtained from 13 liver-transplanted patients 1, 3, 6, 12 or 30 months after transplantation and 11 biopsies were obtained from 11 non transplanted subjects with normal liver tests. The concentrations of the sympathetic neurotransmitter norepinephrine and of epinephrine were determined in liver tissue homogenates. The concentration of norepinephrine was 0.019 +/- 0.05 nmol. g wet liver tissue-1 (mean and SE, n = 32) in the transplanted patients, which was only 1% of the concentration in biopsies from control subjects (2.180 +/- 0.420 nmol.g wet liver tissue-1). The hepatic norepinephrine concentration did not increase significantly over time in liver-transplanted patients during the observation period (0.015 +/- 0.008 nmol.g wet wt-1 (1 month post) (n = 8) vs. 0.024 +/- 0.018 nmol.g wet wt-1 (12 months post) (n = 6) and 0.012 +/- 0.006 nmol.g wet wt-1 (30 months post) (n = 5)) (p < 0.05). The liver tissue concentration of epinephrine was markedly lower in liver-transplanted subjects (0.01 +/- 0.003 nmol.g wet tissue-1) than in control subjects (0.04 +/- 0.007 nmol.g-1) (p < 0.01). This study indicates that within the first years after transplantation, there is no evidence of sympathetic liver nerve reinnervation in liver-transplanted patients. PMID- 8201228 TI - Blunted systemic, splanchnic, and renal hemodynamic responses to atrial natriuretic peptide in rats with cirrhosis. AB - Systemic, splanchnic and renal hemodynamic responses to saline, physiological (25 ng.kg-1.min-1) and pharmacological (100, 300 and 600 ng.kg-1.min-1) doses of alpha human atrial natriuretic peptide were measured in normal (n = 7 for saline and 7-8 for each dose of atrial natriuretic peptide) and cirrhotic (n = 7 for saline and 7-8 for each dose of atrial natriuretic peptide), conscious, unrestrained rats. In addition, plasma norepinephrine concentrations were measured in normal and cirrhotic rats, before and following a 300-ng.kg-1.min-1 dose of atrial natriuretic peptide. In cirrhotic rats, splanchnic, renal and systemic hemodynamics were not significantly affected by either physiological or pharmacological doses of atrial natriuretic peptide. In normal rats, a 300 ng.kg 1.min-1 dose of atrial natriuretic peptide significantly decreased cardiac index, portal tributary blood flow and renal blood flow, and significantly increased vascular resistance in the systemic, portal, and renal territories. The other doses of atrial natriuretic peptide did not significantly change regional and systemic hemodynamics. Atrial natriuretic peptide-induced changes in plasma norepinephrine concentrations were significantly higher in normal than in cirrhotic rats (1827 +/- 834 vs. 59 +/- 46 pg/ml, mean +/- S.E., respectively). In conclusion, this study shows that the normal cardiovascular response to a 300 ng.kg-1.min-1 atrial natriuretic peptide infusion is blunted in cirrhotic rats. Moreover, in cirrhotic rats, blunting of vasoconstriction following atrial natriuretic peptide administration seems to be due to a lack of increased sympathetic vascular tone. PMID- 8201230 TI - Predominance of gram-positive microorganisms as a cause of septicemia in patients with hematological malignancies. AB - OBJECTIVE: To ascertain the etiology and outcome of episodes of bacteremia and fungemia over a three-year period (1990-1992) in patients with hematological malignancies. DESIGN: Retrospective study. SETTING: Hematology service of a 1,500 bed Spanish university hospital. RESULTS: Of a total of 178 episodes of significant bacteremia or fungemia in 101 patients, 53% affected patients with acute leukemia. Gram-positive microorganisms were found to be the cause in 70% of the monomicrobial episodes. The most frequently isolated microorganism was coagulase-negative Staphylococcus (35%), followed by Staphylococcus aureus (11%). Most blood-stream infections occurred during an episode of neutropenia (59%). A total of 34 patients died during hospitalization; in 14, infection was the cause of death. CONCLUSIONS: A marked increase in the incidence of bacteremias caused by gram-positive microorganisms has been observed in our hospital over the last 10 years, especially in patients with hematological malignancies. The mortality due to bacteremia is similar to that found by other authors in series of bacteremia in hematological patients, and we have not found significant differences in the mortality due to bacteremia between neutropenic and non neutropenic patients (Infect Control Hosp Epidemiol 1994;15:101-104). PMID- 8201232 TI - Variation in medical practice: implications for the hospital epidemiologist. PMID- 8201231 TI - Methicillin-resistant Staphylococcus aureus (MRSA): a briefing for acute care hospitals and nursing facilities. The AHA Technical Panel on Infections Within Hospitals. PMID- 8201233 TI - Distribution of HIV-contaminated blood prompts closer monitoring of blood supply programs. PMID- 8201234 TI - Control of MRSA in a long-term care facility. PMID- 8201235 TI - Prolonged, multipatient use of oxygen humidifier bottles. PMID- 8201236 TI - Reducing laundry linen sharps contamination: employee safety management. PMID- 8201237 TI - Control of methicillin-resistant Staphylococcus aureus: the ambivalence persists. PMID- 8201238 TI - Epidemiology of Staphylococcus aureus infections in patients on hemodialysis. AB - OBJECTIVE: To determine the epidemiology of Staphylococcus aureus infections in hemodialysis patients. METHOD: S aureus isolates from surveillance cultures and from sites of infection were evaluated by both bacteriophage typing and restriction endonuclease digestion of plasmid DNA. SETTING: A hemodialysis unit in Brugge, Belgium. ORGANISMS: S aureus isolates from 11 chronic hemodialysis patients who had participated in the placebo arm of a previously reported placebo mupirocin comparative study. RESULTS: Of 75 S aureus isolates evaluated, 63 were from cultures of nares and 12 from infections (three arteriovenous fistula infections, four wound infections, and five bacteremias). All isolates were typed by bacteriophages and 56 (75%) had plasmids. Three patients developed 12 infections. Eleven infections were caused by isolates previously identified in surveillance cultures. Only one infection was caused by a strain not identified previously in surveillance cultures. CONCLUSION: These results support the hypothesis that S aureus isolates causing infections in hemodialysis patients are of endogenous origin. PMID- 8201239 TI - Bacterial contamination of platelets at a university hospital: increased identification due to intensified surveillance. AB - BACKGROUND: A cluster of bacterial contamination of platelets occurred at a university hospital in a one-month period. This unusual clustering allowed us to examine the likely mechanism of contamination and clinical sequelae. METHODS: We reviewed medical records of patients receiving random donor platelet transfusions to determine numbers of platelets transfused, reactions reported, and episodes of bacterial contamination. We also reviewed procedures at the collecting blood agencies and the hospital blood bank. RESULTS: Four patients received bacterially contaminated platelets during June and July 1991. The rates of reported platelet transfusion reactions increased significantly (P < 0.001) from September 1989 through July 1991 (study period); in addition, the rate of contamination of platelets during June and July 1991 was 23-fold higher than during the previous 21 months (P < 0.001). Surveillance methodology changed dramatically during the study period, contributing to the recognition of the current cluster. Pathogens isolated from the contaminated platelet pools were Bacillus cereus, Staphylococcus epidermidis, or Pseudomonas aeruginosa in titers ranging from 10(6) to 10(8) colony forming units/mL. Four constituent individual platelet units identified as the probable cause of the outbreak (including one postepidemic episode) were significantly older (mean age, 4.8 days) than 106 randomly selected individual platelet units (mean age, 3.7 days; P = 0.04). Platelet pools were transfused an average of 2.5 hours after pooling. Review of blood collection and platelet preparation practices did not identify breaks in procedure or technique that could have caused contamination. CONCLUSIONS: Increased awareness of platelet transfusion reactions by clinical staff and routine culturing of all platelets associated with transfusion reactions will identify contaminated platelets. Identification of contaminated platelets is necessary to treat affected patients appropriately and to determine the prevalence of and risk factors for contaminated platelets (Infect Control Hosp Epidemiol 1994;15:82-87). PMID- 8201240 TI - Epidemic Clostridium difficile-associated diarrhea: role of second- and third generation cephalosporins. AB - OBJECTIVE: To better define the role of multiple risk factors for cytotoxic Clostridium difficile-associated diarrhea. DESIGN: Case-control study. SETTING: A Veterans Affairs Medical Center. PATIENTS: Thirty-three case patients with C difficile-associated diarrhea. Two control groups were used: one group consisted of 32 patients from the same ward as the case patients, and one group consisted of 34 patients with nosocomial diarrhea and negative C difficile toxin assays. INTERVENTION: None. RESULTS: Multivariate analyses revealed that exposure to second- or third-generation cephalosporins was the most important independent risk factor, even after controlling for other antimicrobial use (odds ratio [OR] = 8.3, 95% confidence interval [CI95] = 1.4 to 48.9 compared to ward controls; OR = 9.6, CI95 = 2.1 to 44.1 compared with diarrhea controls). Persons exposed to two or more antimicrobials simultaneously were at substantially elevated risk (OR = 18.7, CI95 = 4.1 to 85.8 compared with ward controls; OR = 21.5, CI95 = 3.2 to 141.9 compared with diarrhea controls). CONCLUSION: Physicians should consider carefully the appropriateness of second- and third-generation cephalosporin use and combination antimicrobial therapy, especially during nosocomial C difficile associated diarrhea outbreaks (Infect Control Hosp Epidemiol 1994;15:88-94). PMID- 8201241 TI - Screening of physicians for tuberculosis. AB - OBJECTIVE: To determine the prevalence of tuberculous infection among a sample of physicians at Barnes Hospital and to determine the frequency of tuberculin skin testing and the adequacy of follow-up for physicians with positive tuberculin skin tests. DESIGN: Convenience sample. SETTING: 1,000-bed, university-affiliated tertiary care hospital. SUBJECTS: Physicians attending departmental conferences were screened for tuberculosis. Prior history of tuberculosis, antituberculous therapy, BCG vaccination, and previous tuberculin skin test results were obtained with a standardized questionnaire. Tuberculin skin tests were performed on those who were previously skin-test negative. OUTCOME MEASURE: Tuberculosis infection, prophylactic therapy. RESULTS: Eighty-six (24.5%) of 351 physicians in the study were skin test positive by history or currently performed skin test. Of 61 who reported a previously reactive skin test, 40 (66%) had been eligible for isoniazid prophylaxis, but only 15 (37.5%) of 40 had completed at least six months of therapy. Of 290 physicians reporting a previously negative skin test, 25 conversions (8.6%) were identified. Previously undiagnosed, asymptomatic pulmonary tuberculosis was identified in one physician. CONCLUSIONS: Infection with Mycobacterium tuberculosis is common among physicians. Physicians were screened irregularly for tuberculosis, and the use of prophylactic therapy was inconsistent. Aggressive tuberculosis screening programs for healthcare workers should be instituted (Infect Control Hosp Epidemiol 1994;15:95-100). PMID- 8201243 TI - Cloning of new 5-HT receptors. PMID- 8201242 TI - The pharmacology of the 5-HT4 receptor. AB - Dumuis and colleagues (1988) in their investigation of a 5-HT receptor positively linked to adenylate cyclase in the central nervous system, concluded that the receptor was not 5-HT1, 5-HT2 or 5-HT3-like and suggested that it belonged to a new class of 5-HT receptor called 5-HT4. A similar, if not identical receptor was located by Craig and Clark (1990) in the guinea pig ileum and a functional role for the peripheral 5-HT4 receptor has since been established in many species to mediate muscle contraction or relaxation within the gut and positive inotropic effects in the heart. In contrast, a functional role for central 5-HT4 receptors has remained obscure. Using measurements of rodent behaviour in the mouse light and dark test box and rat social interaction, anxiolytic agents such as diazepam and putative anxiolytic agents such as the 5-HT1A and 5-HT3 receptor ligands 8-OH DPAT and low doses of tropisetron release behaviour suppressed by the aversive situation. 5-Hydroxytryptophan has the opposite effect exacerbating the behavioural response to the aversive situation. But an anxiolytic profile is revealed by co-treatment with ritanserin plus 5-hydroxytryptophan. The drug induced anxiolytic profiles are inhibited by SDZ205-557 and a high dose of tropisetron. Both compounds are 5-HT3/5-HT4 receptor antagonists yet the selective 5-HT3 receptor antagonist ondansetron fails to inhibit the drug-induced anxiolytic profiles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201244 TI - The breadth of action of the 5-HT3 receptor antagonists. AB - The breadth of action of 5-HT3 receptor antagonists to modify animal behaviour may at first appear surprising but is revealing of a widespread role for 5-HT in moderating behaviour. It will prove of considerable interest to establish the role of the 5-HT3 receptor antagonists in the treatment of human illness. Such data would not merely be relevant to the design of new drug therapies but would also allow an important insight into the value of the animal models of human psychiatric disease. PMID- 8201245 TI - The serotonin system and aggressive personality disorder. PMID- 8201247 TI - Serotonergic mechanisms in psychiatric disorders: new research tools, new ideas. PMID- 8201246 TI - The use of tryptophan depletion to evaluate central serotonin function in depression and other neuropsychiatric disorders. AB - The results from these and other studies provide an opportunity to critically re examine the role of brain monoamine function in the pathophysiology of depression and the mechanism of action of antidepressant drugs. The following observations are most salient: 1. Tryptophan depletion, which reduces brain serotonin function, reverses the therapeutic effects of specific serotonin reuptake inhibitors (SSRIs) but not drugs which potently inhibit noradrenaline reuptake. In contrast, depletion of noradrenaline and dopamine, as a consequence of AMPT administration, reverses the remission induced by noradrenaline (desipramine) and dopamine (mazindol) reuptake inhibitors, but not SSRIs. These data suggest that the efficacy of antidepressant drugs may not be due to a common mechanism involving a single monoamine system. SSRIs and noradrenaline reuptake inhibitors may work via primary actions on serotonin and noradrenaline function, respectively. Alternatively, these two classes of antidepressant drugs may exert their therapeutic properties by affecting the function of an, as yet, unknown neuronal system that is regulated by these monoamine systems; 2. In both drug free depressed patients and healthy subjects, tryptophan depletion and AMPT do not produce marked alterations in depressed mood. These results suggest that alterations in serotonin, dopamine, and noradrenaline systems may not reflect the primary pathology causing depressive illness. An alternative explanation is that in depressed patients these systems are maximally dysfunctional such that further manipulations do not worsen depressive systems. 3. Clinical experience and the results from several controlled studies indicate that the efficacy of SSRIs and noradrenaline inhibiting drugs are approximately equal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201248 TI - The serotonin hypothesis of obsessive compulsive disorder. AB - The above studies investigating the responsivity of the 5-HT system to provocation provide some support for the hypothesis drawn from the results of pharmacologic treatment trials and studies of biological markers that dysregulation of the 5-HT system may be involved in the pathogenesis of OC symptoms. While results of several studies document blunting of neuroendocrine responses to 5-HT agonists, only one study suggests a small increase in responsiveness compared to healthy controls. Combined with neurophysiologic data suggesting net increases in 5-HT functioning following treatment with SRIs, these results suggest that the primary deficit in OCD is not one of increased 5-HT responsivity. Exacerbation of OC symptoms sometimes observed during mCPP challenge is not entirely consistent with this hypothesis and additional studies are required to clarify the significance of these findings. However, behavioral hypersensitivity coupled with neuroendocrine hyposensitivity to serotonergic stimulation might characterize the serotonergic dysfunction accompanying OCD. The complexity of the 5-HT system, and the likelihood that behavioral and neuroendocrine responses are mediated by different receptor subtypes makes this hypothesis entirely plausible. The efficacy of SRIs in the treatment of OCD remains the firmest evidence of serotonergic involvement in this condition. Results of challenge studies in OCD also suggest a possible dysregulation in 5-HT function, although the precise nature of this disturbance remains elusive. Neuroendocrine responses to 5-HT agonists generally are consistent with a tendency toward hyposensitivity in OCD. Behavioral results, while more mixed, indicate a hypersensitivity to 5-HT agonists. Further refinement in dependent and independent variables used in challenge studies may clarify remaining questions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201249 TI - Suicide prevention and serotonergic drugs. AB - It is sometimes assumed that all antidepressants have a beneficial effect in reducing suicidal ideation or tendencies but there is evidence to suggest a better effect with some and that others may even provoke suicide attempts. Possible provocation of suicide attempts may be invoked to explain the high rate of attempts reported in a study with maprotiline compared with placebo and the higher rate of deaths from overdose seen with some tricyclic antidepressants. Serotonin reuptake inhibitors have been rather consistently reported to have an advantage in reducing suicidal ideation and have been shown to have a protective effect against the emergence of suicidal thoughts. In a direct test of the effect of serotonin reuptake inhibitors on suicidal behaviour there was no provocation of suicide attempts. PMID- 8201250 TI - Dysthymia and serotonin. PMID- 8201251 TI - Mood, food and 5-HT. PMID- 8201252 TI - Withdrawal of aegis? So what's that? PMID- 8201253 TI - Allegations of impropriety in manuscripts by Aws S. Salim: examination and withdrawal of journal aegis. The Executive Editorial Committee of the Journal of Laboratory and Clinical Medicine. PMID- 8201254 TI - Postmenopausal hormone-replacement therapy, plasma lipoprotein[a], and risk for coronary heart disease. PMID- 8201255 TI - When pathology is normal. PMID- 8201256 TI - Rhapsody in red. PMID- 8201257 TI - Newly recognized causes of atherosclerosis: the role of microorganisms and of vascular iron overload. AB - We have hypothesized that shear stresses at sites of increased vascular turbulence may foster atherogenesis by two previously unknown mechanisms: The first involves Herpes virus activation, which can provoke direct or inflammatory cell-mediated endothelial damage while altering the vascular surface to a highly procoagulant entity. The second derives from red blood cell fragmentation, with resulting uptake by endothelium of released heme groups. In this instance the opening of the heme ring by induced endothelial heme oxygenase frees iron, which sensitizes cells to damage by oxidants--for instance, those generated by closely apposed inflammatory cells. An additional injurious effect of released heme results from its potent catalysis of LDL oxidation--a process specifically and rapidly inhibited by oral supplementation of vitamin E. Although heme-protein's deleterious actions can be counteracted by the plasma constituents haptoglobin and hemopexin, we suggest that these may not be sufficiently present in "sanctuary" sites of vessel walls such as in intramural hemorrhages associated with atherosclerotic intimal tears. PMID- 8201258 TI - The p53 tumor suppressor gene. PMID- 8201259 TI - Interleukin-6: a cytokine with potential diagnostic and therapeutic roles. AB - Interleukin-6 is a pleiotropic cytokine and may be a pivotal mediator in the pathogenesis of shock and sepsis, in modulating megakaryocytopoiesis, and in inhibition of tumor growth. Among characteristics of interleukin-6 are regulation of expression of other cytokines, induction of differentiation and proliferation of normal and malignant cells, and inhibition of tumor growth in vivo under experimental conditions. As a major inducer of the acute phase response, interleukin-6 is produced and sets off a chain of events as it acts on effector targets. Preclinical anti-tumor studies with interleukin-6 have provided rationale for probing its role in the therapy of malignancy. The probability is that in the near future interleukin-6 will have established clinical roles as a protein of diagnostic and therapeutic import. PMID- 8201260 TI - Unilateral lung injury caused by ischemia without hypoxia in isolated rat lungs perfused with buffer solution. AB - It has not been clear whether or not pulmonary ischemia-reperfusion injury would occur while ischemic lungs were maintained in a well-oxygenated state. Our aim was to develop an ischemic lung model whose oxygen tension was maintained and to determine whether or not ischemia without hypoxia would injure the lung. Rat lungs isolated, ventilated, and perfused with Krebs-Henseleit solution (0.04 ml/gm body weight) were obtained by a standard technique, and the left and right pulmonary arteries were isolated to enable selective perfusion to either lung. After the left lung was exposed to ischemia for 60 minutes with ventilation maintained by a normoxic (20% O2, 5% CO2, 75% N2; normoxia) or a hyperoxic (95% O2, 5% CO2; hyperoxia) gas mixture, it was reperfused for 30 minutes either in a forced way (occluding the right pulmonary artery for 10 minutes followed by perfusion of both lungs for another 20 minutes) or in the natural way (distribution of flow dependent on vascular resistance) to compose three experimental groups (forced reperfusion-normoxia, natural reperfusion-normoxia, and forced reperfusion-hyperoxia).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201261 TI - Postmenopausal cyclic estrogen-progestin therapy lowers lipoprotein[a]. AB - In 21 postmenopausal women, ages 45 to 55 years, we assessed the effects of 3 months of cyclic estrogen-progestin therapy on lipoprotein[a] (Lp[a]), lipids, lipoproteins, apolipoproteins, blood pressure, and insulin/glucose relationships. After a pretherapy baseline study, conjugated estrogens (0.625 mg for 21 days) and medroxyprogesterone acetate (5 mg last 10 days) were given to the women cyclically for 3 months, and then the study was repeated. During hormone replacement therapy, mean plasma Lp[a] fell 25% (from 20 to 15 mg/dl) (p = 0.0001), apolipoprotein B fell 14% (p = 0.01), and triglyceride fell 15% (p = 0.01), while high-density lipoprotein cholesterol (HDLC) rose 26% (p = 0.0001) and apolipoprotein A1 rose 25% (p = 0.003). The area under the insulin curve after oral glucose tolerance fell 33% (p = 0.0001), while the ratio of insulin area to glucose area fell 22% (p = 0.006). Mean systolic and diastolic blood pressure fell, respectively, 6% and 10% (p = 0.0001 for both). We speculate that the potential cardioprotective effect of estrogen-progestin therapy in postmenopausal women may be mediated through lowering Lp(a) as well as raising HDLC and apolipoprotein A1, lowering apolipoprotein B and blood pressure, and decreasing insulin resistance. PMID- 8201262 TI - Unrecognized dyslipoproteinemia in United Kingdom families recruited to a genetic register because of unexplained coronary heart disease. AB - A register was built up of DNA from United Kingdom families with premature coronary heart disease and no perceived risk associations in the expectation that obscure causal factors could be defined through future genetic analysis. Referrals came from interested, predominantly cardiologic units in southern England. For inclusion, probands had documented coronary heart disease before age 55 years that was regarded as unexplained, in families with at least two living affected first-degree and two other members, in most families over two generations. Referred probands and family members completed a questionnaire on general health and habits and were examined for body mass index, blood pressure, resting electrocardiogram, and lipoprotein profile. Data are presented on 276 living members from 26 families, representing 75.4% of all members age 15 years and older. The striking observation was the extent of dyslipoproteinemia that was not identified by the referring units as relevant to the expression of accelerated coronary heart disease. This was expressed as hypercholesterolemia, reduced levels of high-density lipoprotein, or both, in comparison with profiles recorded over the same period and for a similar but unselected general British population. Further genetic analysis for a major occult risk factor in these families is inappropriate. Present concerns with potential adverse associations with low cholesterol, or with lipid-lowering treatment, should be addressed in the knowledge that uncontrolled dyslipoproteinemia also has severe adverse associations. These associations are still not widely appreciated in the management of patients and families with premature coronary heart disease. PMID- 8201263 TI - Treatment of Wilson's disease with zinc. XIII: Therapy with zinc in presymptomatic patients from the time of diagnosis. AB - The siblings of patients with newly diagnosed Wilson's disease are each at 25% risk of also having this autosomal recessive disease. Screening these siblings allows their detection and institution of prophylactic therapy before they become clinically ill. Herein we report the successful treatment of 13 presymptomatic patients with zinc acetate. These patients who received zinc have been followed for 3 to 9 years. In well-complying patients, 24-hour urine copper and non ceruloplasmin plasma copper levels have decreased over years of follow-up, consistent with the elimination of the excess easily mobilized copper (the potentially toxic copper) of the body. Effect of therapy and compliance are easily monitored by following 24-hour urine zinc and copper levels. The urine copper level is a good reflection of the body's excess load of easily mobilizable copper. It will increase if control is not adequate. A decrease in urine zinc is an early signal that the patient's compliance is not optimal. The levels of hepatic copper in response to several years of zinc therapy may remain the same, go down, or go up temporarily. This is a reflection of zinc induction of hepatic metallothionein, which sequesters copper in a non-toxic pool. Hepatic copper levels should not be used to manage therapy. Liver function is well preserved by zinc therapy, and no zinc toxicity occurred in these 13 patients. No patient developed symptoms related to Wilson's disease. We conclude that zinc acetate is a fully effective and non-toxic therapy for the prophylactic treatment of the presymptomatic Wilson's disease patient. PMID- 8201264 TI - Complement activation in platelet concentrates is surface-dependent and modulated by the platelets. AB - Activation of platelets during storage may contribute to the loss of function and viability known as the platelet storage lesion. We investigated the role of complement activation as a possible mediator of the platelet storage lesion. We studied platelet bags stored up to 5 days under standard blood bank conditions and monitored the generation of several complement activation fragments from both the classical and alternative pathways. To assess the role of noncellular artificial surfaces in the activation of complement, parallel bags were prepared containing platelet-poor plasma. The levels of C4d and C3a increased steadily over time in storage, as did the level of the inactivated membrane attack complex SC5b-9. Generation of C4d, C5a, and SC5b-9 was greater in the absence of platelets than when platelets were present in the container. C5a levels in both groups were low and remained so during storage, suggesting that the C5a generated became surface associated. Using flow cytometry we detected C3 and C3a, but not C9, on the platelet surface. The percentage of C3-positive platelets peaked at the third day of storage; by day five platelet-associated C3 had declined. Decay accelerating factor expression on the platelet surface increased with time in storage and in parallel with CD63 expression. Based on the C4d levels, complement activation proceeded via the classical pathway; minimal generation of the alternative pathway activation fragment. Bb was seen in either the presence or absence of platelets. As an indirect measure of the activation of C1, the functional level of C1 esterase inhibitor (C1INH) was determined. C1INH levels declined over time in storage in bags containing only plasma; however, in the presence of platelets, the levels remained constant presumably because of release of C1INH from the alpha-granules of activated platelets. PMID- 8201265 TI - Immunologic cross-reactivity of acid anhydrides with immunoglobulin E against trimellityl-human serum albumin. AB - The purpose of this study was to determine whether workers sensitized by one acid anhydride, trimellitic anhydride (TMA), would possibly react immunologically to two other acid anhydrides, phthalic anhydride (PA) or maleic anhydride (MA). We studied serum samples from four workers with TMA asthma and immunoglobin E (IgE) against TMA conjugated to human serum albumin (TM-HSA). In enzyme-linked immunosorbent assay (ELISA) cross-inhibition studies, TM-HSA inhibited IgE binding to TM-HSA, but when 100 times more P-HSA or M-HSA was used, no significant inhibition occurred. However, in ELISA studies of P-HSA and M-HSA, we saw binding of specific serum IgE. Finally, in passive transfer studies in rhesus monkeys with serum from an individual with antibodies to all three acid anhydrides, the following titers were obtained: TM-HSA (1:32), P-HSA (1:8), M-HSA (negative). We conclude that cross-inhibition studies may not be the best method for determining whether an individual sensitized to one antigen will react to a related antigen. The determination of biologic reactivity in a rhesus monkey model of passive cutaneous transfer makes it likely that biologic reactivity would also occur in a human sensitized to TMA and then exposed to another anhydride such as PA. PMID- 8201266 TI - Granulocyte proteases and hydrogen peroxide synergistically inactivate thrombomodulin of endothelial cells in vitro. AB - Leukocytes release lysosomal proteases and reactive oxygen species in response to various stimuli that damage the adjacent endothelial cells. We investigated the effects of granulocyte lysosomal proteases (granulocyte elastase [GE] and cathepsin G [CG] and/or hydrogen peroxide (H2O2) on thrombomodulin (TM) activity of endothelial cells. We wished to determine whether the activated leukocytes damage the nonthrombogenic systems of endothelial cells. When cultured human umbilical vein endothelial cells (HUVECs) were incubated with GE, TM activity of the cells (as judged by the protein C activation capacity) decreased to about 10% of control with the concomitant increase of immunoreactive TM concentration in the conditioned media. CG also decreased TM activity to about 20% of control with the concomitant increase in immunoreactive TM concentration in the conditioned media. The GE- or CG-induced inactivation of TM was not observed in the presence of alpha 1-proteinase inhibitor. Immunoblot analysis showed that CG cleaved purified TM to yield one major fragment with an M(r) of 43,000; TM activity of this fragment was about 10% of the control activity. When purified TM was incubated with GE, TM activity decreased to 10% of control, and no detectable band was found on immunoblotting, suggesting that CG and GE cleave TM into inactive fragments and that GE degrades the epitope structure of TM. Although H2O2 (1.0 mmol/L) enhanced chromium 51 release from prelabeled HUVECs after 30 minutes of incubation, it decreased TM activity only slightly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201267 TI - Urea-derived cyanate forms epsilon-amino-carbamoyl-lysine (homocitrulline) in leukocyte proteins in patients with end-stage renal disease on peritoneal dialysis. AB - Carbamoylated proteins have been located by using a site-specific polyclonal antihomocitrulline antibody and a fluorescent secondary antibody in leukocytes from patients with end-stage renal disease who were undergoing maintenance continuous ambulatory peritoneal dialysis. A covalent reaction with urea-derived cyanate and the epsilon-amino group of lysine forms homocitrulline residues in carbamoylated proteins. Isocyanic acid, the reactive form of cyanate, is spontaneously formed from urea in aqueous solution at physiologic pH and temperature. In washed, fixed monolayers of cells, an intracellular fluorescent antigen-antibody complex was located throughout the cytoplasm of polymorphonuclear neutrophils (PMNs) and monocytes from 11 patients with blood urea nitrogen (BUN) levels ranging from 32 to 102 mg/dl who were undergoing dialysis for 2 to 135 months. A punctate fluorescence present in the cell surface proteins of living cells demonstrated that lysine residues in the external domain of proteins were carbamoylated, forming homocitrulline. In contrast, we found a perinuclear fluorescence in PMNs in normal subjects with no history of renal insufficiency and BUN levels of 6 to 19 mg/dl. This suggests that homocitrulline is located in carbamoylated proteins within the perinuclear membrane, a structural organelle continuous with the endoplasmic reticulum. It appears that continuous exposure to urea-derived cyanate in low levels results in increasing carbamoylation of stable proteins over the PMN's lifetime. When normal PMNs were exposed to 120 mmol/L cyanate ion in vitro for 10 to 30 minutes, the ability of PMNs to release microbicidal superoxide was strongly inhibited. Thus protein carbamoylation may provide a regulatory mechanism. The altered function of PMNs in renal disease may be due in part to the posttranslational modification of proteins by urea-derived cyanate. PMID- 8201268 TI - Normal acid-base equilibrium in acute hyponatremia and mixed alkalosis in chronic hyponatremia induced by arginine vasopressin or 1-deamino-8-D-arginine vasopressin in rats. AB - The effects of acute and chronic water intoxication induced by the administration of oral water and arginine vasopressin (AVP) or 1-deamino-8-D-arginine vasopressin (DDAVP) on blood acid-base equilibrium and aldosterone, corticosterone, and thyroxine secretion were studied in rats. Acute hyponatremia (3 hours) was associated with normal bicarbonate and blood acid-base equilibrium and a decrease in aldosterone and thyroxine concentrations, while corticosterone was increased. When similar levels of hyponatremia (serum sodium 110 mEq/L) were maintained for 24 or 72 hours, a normal serum bicarbonate concentration was observed, but blood acid-base equilibrium showed a mixed respiratory and metabolic alkalosis. Blood pH was negatively correlated with serum sodium concentration (R = -0.65; p < 0.001), as was the metabolic alkalosis (base excess; R = -0.64; p < 0.001) and the aldosterone concentration (R = -0.52; p < 0.01), while the PCO2 was positively correlated (R = +0.49; p < 0.01). Hyperaldosteronism was similar whether hyponatremia was induced with AVP or DDAVP and was observed even for mild hyponatremia. When hyponatremia was induced by a high water and salt intake (2.5% D-glucose, 0.45% NaCl; 15% body weight), aldosterone concentration was as high (about three times control values) as in rats with similar levels of hyponatremia but with a salt-free diet. The high salt intake was associated with a more severe metabolic alkalosis (base excess +5,5 mEq/L). In chronic hyponatremia, corticosterone and thyroxine values were normal. In hyponatremia related to syndrome of inappropriate secretion of antidiuretic hormone, the normal serum bicarbonate level is an expected observation; as in acute water intoxication, it stays normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201269 TI - A naturally occurring model of immunoglobulin E antibody-mediated hypersensitivity in laboratory animals. AB - A naturally occurring model of immunoglobulin E (IgE) antibody-mediated hypersensitivity in canine and rhesus monkey species to environmental allergens is described. Cutaneous responses to a dust mite mix (Dermatophagoides farinae/pteronyssinus) and to four storage mite extracts (Aleuroglyphus ovatus, Blomia tropicalis, Chortoglyphus sp., Lepidoglyphus destructor) occurred in the canine species. Rhesus monkeys had IgE antibody-mediated hypersensitivity to dust mite on cutaneous challenge, but to a lesser degree than the canine species. Biologic relevance was verified by eliciting positive airway challenges in both species. The IgE antibody-mediated basis of these responses was confirmed by passive transfer technique. Demonstration of dust mite allergy provides a naturally occurring model of IgE antibody-mediated hypersensitivity in the canine and rhesus monkey species. Storage mite IgE antibody-mediated hypersensitivity exists in the canine species. PMID- 8201270 TI - Progressive inactivation of cathepsin G and elastase released from activated neutrophils in vitro: lack of participation of the neutrophil alpha 1-proteinase inhibitor. AB - Addition of platelets to activated human polymorphonuclear neutrophils (PMNs) led to their aggregation and degranulation, with these responses decreasing as a function of the time interval between PMN activation and platelet addition. Thus, for a 15-second interval platelet aggregation and serotonin release reached 51.3% +/- 6.7% (n = 11) and 64.3% +/- 4.9% (n = 8), respectively, but after a 5-minute interval they were totally absent. This effect was correlated with the decrease in enzymatic activities of elastase (HLE) and cathepsin G (CAT-G) that were released on PMN activation and responsible for the activation of nearby platelets (r = 0.86 and 0.90 for CAT-G and HLE, respectively; p < 0.05). Because it has been recently shown that PMNs express an alpha 1-proteinase inhibitor (alpha 1 Pl) gene and secrete this antiproteinase at their surface, we investigated whether the PMN alpha 1-Pl could regulate the biologic activities of both proteinases. Although superoxide anions oxidize alpha 1-Pl and reduce its affinity for CAT-G and HLE, maneuvers aimed at modifying their concentrations did not modify the loss of CAT-G and HLE. In fact, the progressive decrease of the two proteinase enzymatic activities followed the same pattern whether PMNs were present or not. It is concluded that PMN alpha 1-Pl is not involved in the time dependent inactivation of CAT-G and HLE released from activated PMNs. PMID- 8201271 TI - Effects of dietary fat content, saturated fatty acids, and fish oil on eicosanoid production and hemostatic parameters in normal men. AB - Populations that consume a diet rich in marine lipids have been reported to have a lower risk of coronary heart disease. However, some Western population groups with a high fish consumption continue to suffer elevated rates of coronary heart disease. Many of these individuals consume a diet rich in saturated fats in addition to the fish. To examine these possible dietary interactions we fed six healthy men diets that contained two levels of saturated fat (5% and 19% of energy). During 3-week periods the study subjects were given diets with a low (25% of energy) and high-(39% of energy) fat content with and without inclusion of n-3 polyunsaturated or monounsaturated fatty acids (2% of energy). The effects of the n-3 fatty acids on the principal plasma lipid fractions were similar regardless of the saturated fat intake. Platelet function, as measured by the skin bleeding time, was inhibited when n-3 fatty acids were added to the low saturated-fat diet. In vivo thromboxane A2 production as assessed by urinary metabolites also declined (p < 0.01) during supplementation with n-3 fatty acids to a low-fat diet. Prostacyclin production were reduced on a low-fat diet compared to a high-fat diet regardless of supplementation with n-3 fatty acids. N 3 fatty acids stimulated the synthesis of modest amounts of thromboxane A3 and prostacyclin I3, on both the low and high saturated-fat diets. These studies showed that the effects of eicosapentaenoic and docosahexaenoic acids on platelet and vascular function and eicosanoid production are modulated by the content of saturated fatty acids in the diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201272 TI - Effect of streptozotocin-induced diabetes and islet transplantation in proximal skeletal muscle: a histochemical and morphometric analysis. AB - The effect of pancreatic islet transplantation on the development of diabetic myopathy in streptozotocin-induced diabetic Lewis rats was examined histochemically and morphometrically in a proximal striated (rectus femoris) muscle. Diabetes was induced by streptozotocin administration, and diabetic animals were transplanted by intraportal grafts 6 weeks later. Islet-transplanted rats returned to euglycemia usually within the first 24 hours after transplantation and remained euglycemic over the subsequent 12-week observation period. Transplanted animals were compared with age-matched nontransplanted diabetic rats and nondiabetic age-matched control rats. Successful isotransplantation completely prevented the characteristic fast twitch (type IIB, glycolytic) fiber atrophy and also the changes in the fiber-type relative percentages, with prevention of the significant increase in the frequency of slow twitch oxidative (type I) and fast oxidative/glycolytic (type IIA) fibers at the expense of fast twitch glycolytic (type IIB) fibers. The histochemical appearance of all fiber types studied from muscles in transplanted rats was identical to equivalent fibers in age-matched control rats. Our data suggest that diabetic muscle pathology could be reversed and the progression of diabetic amyotrophy halted through the restoration of a euglycemic state by successful pancreatic islet transplantation, at least in short-term experimental diabetes. PMID- 8201273 TI - Shear stress modulates erythropoietin secretion and explains unexpectedly low erythropoietin levels. PMID- 8201274 TI - Federal and state regulation of medical waste. PMID- 8201275 TI - The dilemma over foreign-language labeling of over-the-counter drugs. PMID- 8201276 TI - Injured consumers and the FDA. Should federal preemption protect medical device manufacturers under a quasi-governmental immunity? PMID- 8201277 TI - Aspects of failed family planning in the United States of America and Germany. PMID- 8201278 TI - Re: RBRVS. PMID- 8201279 TI - On the Journal's new look and the right to self-protection. PMID- 8201280 TI - Guns in the medical literature--a failure of peer review. AB - Errors of fact, design, and interpretation abound in the medical literature on guns and violence. The peer review process has failed to prevent publication of the errors of politicized, results-oriented research. Most of the data on guns and violence are available in the criminologic, legal, and social sciences literature, yet such data escape acknowledgment or analysis of the medical literature. Lobbyists and other partisans continue to promulgate the fallacies that cloud the public debate and impede the development of effective strategies to reduce violence in our society. This article examines a representative sample of politicized and incompetent research. PMID- 8201281 TI - Health care and firearms. PMID- 8201282 TI - The allure of foreign gun laws. PMID- 8201283 TI - Guns: health destroyer or protector? PMID- 8201284 TI - Anatomy of a problem. PMID- 8201285 TI - More safe harbors for toy boats? PMID- 8201286 TI - Philosophy matters to medicine. PMID- 8201287 TI - How Jonsen really views casuistry: a note on the abuse of Father Wildes. AB - Kevin Wildes has recently argued in the Journal that Albert Jonsen's model of casuistry is ill-suited to a secular world context, because this model is rooted in a particular history and because of the moral pluralism of contemporary society in which a content-specific method of moral reasoning cannot readily be deployed. Contra Wildes, two arguments are offered. First, casuistry is not tied exclusively to Roman Catholic theology; casuistry also has deep roots in Classical thought, roots that Jonsen and Toulmin underscore. Second, the context of Roman Catholic theology can be distinguished from the method of casuistry, permitting that method to be deployed successfully in morally pluralistic contexts. PMID- 8201288 TI - Debunking the slippery slope argument against human germ-line gene therapy. AB - This paper attempts to debunk the slippery-slope argument against human germ-line gene therapy by showing that the downside of the slope--genetic enhancement--need not be as unethical or unjust as some people have supposed. It argues that if genetic enhancement is governed by proper regulations and is accompanied by adequate education, then it need not violate recognized principles of morality or social justice. PMID- 8201289 TI - Conflicts over post-exposure testing for human immunodeficiency virus: can negotiated settlements help? AB - Health care workers with needlestick exposures to patients' blood often request a test of the patient for evidence of infection with human immunodeficiency virus. If the patient refuses the test, a conflict develops between the interests of the health care worker and those of the patient. Traditional approaches to this dilemma attempt to balance the rights or utilities of abstract patients and health care workers. While these approaches have the advantage of offering clear guidelines in advance of conflict, the interests of the actual participants may differ from those used to create the guidelines. In nonmedical settings, conflicts are often resolved efficiently through negotiation and monetary exchanges. Although negotiated monetary settlements between health care workers and patients may be an impractical way to resolve medical conflicts, models developed from these perspectives provide insights into the individual interests of physicians and patients. Changing existing rules about medical record documentation, or increasing the penalties for the misuse of medical information, may satisfy the interests on both sides of the conflict and so represent integrative bargaining solutions. Even so, as the relationship between health care workers and their patients evolves, more explicit strategies for negotiation may become a reasonable solution to the problem of conflict. PMID- 8201290 TI - The give and take of organ procurement. AB - Scientific developments of the last 20 years have made the transplantation of cadaveric solid organs a viable and expected treatment alternative for patients suffering from various forms of End Stage Organ Disease. Of the number of organs that could be utilized for this, only a small percentage of them are actually made available. North American legislation explicitly categorizes the transfer of cadaveric organs as an anatomical or tissue "gift". The concept of the gift is mediated by transculturally consistent unwritten, but powerfully felt, rules of conduct. Among the most profound elements of the concept is the obligatory gift exchange which is central to the gift-relationship. Obviously, neither of these are permitted by the organ transplant scenario. As a result, dissonance is created within the thought process of the individual which cannot be easily resolved, paralyzing many into inaction. We maintain that the present legal framework, designed to facilitate the transfer of organs, clashes with the human phenomenon of giving, and may actually prevent organs from being made available. In a search for a solution to this gift-relationship dilemma, giving organs is contrasted with taking organs as a basis upon which to ground ethically sound public policy. Liberty-limiting principles and the concept of harm are considered within this context. PMID- 8201291 TI - The morality of clinical research--a case study. AB - The paper is a record of a debate which took place between a group of clinicians and the author concerning a clinical trial of a drug supposed to postpone the time when HIV-patients develop AIDS. A problem with the trial was that on available (inconclusive) evidence it appeared that one patient out of 500 was killed by the drug. The question raised was whether, in view of this evidence, it was morally defensible to go on with the trial. The discussion came to involve general topics such as the appropriate role of the ideal of autonomy as well as more particular topics of quantitative and qualitative risk assessments. The main thrust of the argument is that different conceptions of rationality may provide rationales of conflicting clinical decisions. Philosophy matters to medicine. PMID- 8201292 TI - Observations on the epistemological status of bioethics. AB - Different definitions of bioethics in American and Italian literature are reported. It is argued that they refer to three different conceptions of the epistemological status of bioethics: the first conceives of it as an application of moral principles to biomedical problems, the second as a methodology for the working out of clinical judgement, the third as a broader and interdisciplinary public inquiry. It is suggested that each approach grasps a part of the truth, for each singles out one level of the bioethical work. Bioethics is in fact a complex, three-level form of knowledge. The misunderstanding of this complexity has led to some confusion and to conflicts of attribution among those who are concerned with it. PMID- 8201293 TI - Modulations of membrane potential oscillations with drive, calcium overload, ryanodine, and caffeine. AB - The objective of this study is to determine the conditions that generate overdrive excitation and overdrive suppression in canine cardiac Purkinje tissue superfused in vitro. Drive-induced (3 Hz) perturbations in the membrane potential of a calcium overloaded (induced by strophanthidin) Purkinje fiber (from a canine heart) were differently modulated by caffeine and ryanodine. Whereas the postdrive oscillations in the membrane potential Vos (single or multiple oscillations in the diastole of the action potential) and/or spontaneous rate (postdrive suppression or postdrive excitation [PDE]) depended on the concentration of strophanthidin (PDE occurred at 2.5 x 10(-7) M, and Vos were seen variably at several concentrations), caffeine (2-3 mM) in the presence of a lower concentration of strophanthidin (1.25 x 10(-7) M) induced PDE. At these lower concentrations, either drug administered alone only induced Vos. On the contrary, the characteristic effects of ryanodine (10(-8) M) in the presence of strophanthidin (2.5 x 10(-7) M) were either a consistent postdrive suppression immediately or the induction of a pronounced afterdepolarization ([AD] a depolarization following the repolarization of the action potential) whose amplitude decreased with time and suppression. At higher concentrations of ryanodine (10(-5) M-10(-6) M) in a calcium overloaded tissue (strophanthidin, 1.25 x 10(-7) M) overdrive induced a pronounced AD in most cases, with subsequent depolarization and cessation of activity in less than 20 minutes. Ryanodine alone caused suppression of postdrive diastolic potential at lower concentrations (10( 9) M-10(-8) M), a pronounced AD (amplitude diminished with later drives), and suppression at higher concentrations (10(-6) M-10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201294 TI - Effects of activation sequence on the spatial distribution of repolarization properties. AB - The electrotonic effects of activation spread on the spatial distribution of repolarization properties were studied in animal experiments and with computer simulations. Refractory periods (RPs) were measured at 36 sites within a 1.0 cm2 region of the epicardial surface of the canine pulmonary conus during 37 drives in 11 experiments. In each experiment three or four sites along the perimeter of the region bounding the RP test sites were driven. Activation propagated uniformly during some and nonuniformly during other drives in the same animals. In general, RPs were distributed uniformly when activation spread uniformly and nonuniformly when activation spread nonuniformly. The authors observed RP differences as large as 16 ms between sites with 2 mm separation during drive from some epicardial sites in these normal canine hearts. Indices of nonuniformity of activation and of relative RP values were used to quantify the relation between nonuniformity of activation spread and the spatial distribution of the RP. There was a significant negative correlation between nonuniformity of activation and RP indices during the 19 drives in which activation spread nonuniformly. This indicated that RPs were relatively long at sites where activation spread decelerated and relatively short at sites where activation spread accelerated. When nonuniform activation spread was simulated by introducing high-resistance barriers in a model with fixed anisotropic conductivities, there were marked spatial variations in action potential duration. The spatial variations in action potential duration were negatively correlated to acceleration and deceleration of activation spread. The major new finding of this study is that the spatial distributions of RPs are markedly affected by activation spread. Since both characteristics of activation sequence and nonuniformity of RP distributions have roles in reentrant arrhythmias, the findings suggest that some sites of origin of premature activity may be more arrhythmogenic than others. The findings may also explain why ventricular tachycardia can sometimes be initiated from one but not from other sites in patients undergoing electrophysiologic testing. PMID- 8201295 TI - R peak time prolongation and R peak delay in leads I, V5, or V6. Diagnostic values as signs of myocardial dysfunction in chronic mitral incompetence. AB - On the assumption that maximum R peak time prolongation in the left-sided leads I, V5, or V6 and its time relationship to the S peak time of the maximum S amplitude in leads V1, V2, or V3 (representing dorsally directed forces of ventricular depolarization) could indicate the extent of left ventricular volume overloading and possibly left ventricular systolic function, these variables and the preoperative findings of angiocardiography were compared between patients with chronic mitral incompetence who, late after corrective valve surgery, had either well-preserved radionuclide left ventricular ejection fraction (group 1, n = 36) or radionuclide left ventricular ejection fraction below 50% (group 2, n = 30). Before surgery, group 2 patients had a highly significant lower mean left ventricular ejection fraction, a highly significant greater mean end-systolic volume index, a significantly greater mean end-diastolic volume index, a significantly greater mean maximum R peak time in leads I, V5, or V6, and a significantly greater prolongation of the maximum R peak time above the S peak time in the right precordial leads, as compared with group 1. R peak times greater than 50 ms or the presence of R peak delay (maximum R peak time greater than the S peak time of the maximum right precordial S amplitude) yields less sensitive but highly reliable results in predicting radionuclide left ventricular ejection fraction below 50% with both specificity and positive predictive values of 100%. Thus, in chronic mitral regurgitation surgery should not be delayed if patients present these signs because they are specific markers of irreversibly impaired chamber function. PMID- 8201296 TI - Magnetocardiography and exercise testing. AB - Twenty healthy male subjects (age range, 15-25 years; median, 21 years) underwent magnetocardiography during physical exercise. Significant ST-segment displacements of the magnetic signal were found during exercise at a heart rate of 120 beats/min compared to the magnetic signal at rest (P < .001). Since no significant ST-segment changes were found in the electrocardiogram recorded simultaneously with the magnetocardiogram, it is concluded that the magnetocardiogram shows junctional ST-T segment changes earlier than the electrocardiogram. PMID- 8201297 TI - Effect of respiration on the QT interval. AB - This clinical study was undertaken to investigate the effect of respiration on the QT interval. The QT interval is affected by a variety of factors, including steady changes in heart rate, instantaneous changes in heart rate as in atrial fibrillation, and changes in autonomic tone. Respiration gives rise to cyclical changes in the instantaneous heart rate and autonomic tone. The effect of respiration on the QT interval was analyzed in 25 subjects in sinus rhythm. Cosinor analysis was used to estimate the amplitude of its change from the mean value, its statistical significance, and the timing of the maximum change. Thirteen (52%) subjects revealed significant respiratory change in the QT interval, being the shortest during inspiration in 10 of them. Its amplitude correlated positively with respiratory cycle length (r = .58, P < .01), but not with age, mean heart rate, or the amplitude of change in the RR interval. The mean amplitude of change in the QT interval was 0.8% compared to a change of 2.6% in the RR interval. There is a respiratory variation in the QT interval in subjects in sinus rhythm that is more prominent during slower respirations. However, the amplitude of change in the QT interval is small compared to the change in the RR interval. PMID- 8201298 TI - Dipolar electrocardiotopographic evaluation of ventricular activation in patients with various degrees of coronary artery disease. AB - Dipolar electrocardiotopographic imaging of instantaneous vectorcardiographic QRS vectors represents the ventricular activation front as a bounded area on the spherical image surface. Fuzzy set treatment of the elements of this area allows for the recognition of five classes of ventricular activation: I, abnormal; II, abnormal with normal component; III, normal with abnormal component; IV, marginally normal; and V, normal. In a group of 71 patients with chest pain and various degrees of coronary artery stenosis classes II, III, and IV were most frequently observed in patients with one- or two-vessel disease. The frequency distributions of classes II and III throughout the QRS were bimodal with peaks at 20 and 60 ms after QRS onset, while the frequency distribution of class IV was unimodal with a peak at 30 ms after QRS onset. The advantage of this method is the smoothing of threshold values on a quantitative basis. PMID- 8201299 TI - Significance of resting U wave polarity in patients with atherosclerotic heart disease. AB - The aim of this study was to determine the value of U wave polarity in the electrocardiograms of patients with atherosclerotic heart disease. One hundred twelve consecutive patients with U waves were entered into the study. Forty-eight of them had unstable angina pectoris and 64 had prior myocardial infarction (MI) (20 patients had inferior MI, 35 had anterior MI, and 9 had non Q wave MI). Each of these subgroups was divided into two groups with positive (group 1) and negative (group 2) U waves. All patients in this study underwent routine left ventriculography and coronary angiography. The authors examined coronary arteries and calculated ejection fractions. The authors discovered that patients with unstable angina pectoris or anterior MI (group 2) had three-vessel disease more frequently (P < .05). Also, in these patients, there was more than 90% diameter narrowing in the left anterior descending vessel more frequently (P < .001 in unstable angina pectoris and P < .05 in anterior MI). In patients with unstable angina pectoris, inferior MI, or anterior MI, the authors observed that the ejection fraction was lower in group 2 than in group 1 (P < .001 in unstable angina pectoris, P < .05 in inferior MI, and P < .05 in anterior MI). The authors suggest that negative U waves in patients with unstable angina pectoris or anterior MI may indicate multivessel disease with a severe left anterior descending lesion. Also, in patients with unstable angina pectoris, inferior MI, or anterior MI who had negative U waves, ejection fraction was reduced. PMID- 8201300 TI - Relationship between ventricular rate and cardiac output in mimic experimental atrial fibrillation. AB - In treating atrial fibrillation (AF) the goal of ventricular rate reduction is still not determined. An animal model of AF was developed in which the relationship between ventricular rate and the parameters of cardiac function in AF can be studied. To simulate AF, complete heart block was chemically produced on open-chest dogs. Then, assisted by a portable computer, the ventricles were paced with a series of grossly irregular stimuli of predetermined rates, while atria were paced rapidly (500 beats/min). The resulting electrocardiogram and pressure were indistinguishable from the naturally occurring AF. It was found that in AF with ventricular rates that were lower than that of the control state, cardiac output was decreased. Cardiac output increased and reached a plateau when the ventricular rate increased to the level of the control state and then kept stable up to a rate of 320 beats/min. There was a discrepancy between the effective ventricular rate (rate of beats with pulse pressures > or = 25 mmHg in the femoral artery) and the electrical ventricular rate. When the electrical ventricular rate increased over the control ventricular rate the effective ventricular rate did not increase in a parallel manner. Rather, the effective ventricular rate leveled off at the control ventricular rate. This discrepancy may explain the parallel relationship between the effective ventricular rate and cardiac output. PMID- 8201301 TI - Serum calcium and the ECG in patients with primary hyperparathyroidism. AB - Primary hyperparathyroidism (HPT) is associated with cardiovascular disease, but there are no systematic studies on the electrocardiographic findings in HPT. Preoperative electrocardiograms from 139 patients with primary HPT and 97 control patients were therefore investigated. Serum calcium levels were found to be significantly correlated to the QRS amplitude (r = .26, P < .002), ST-segment duration (r = -.55, P < .0001), QT interval (r = -.64, P < .0001), and T wave duration (r = .19, P < .009). These relations were still significant when the influence of age, sex, and blood pressure level were taken into account in the multiple regression analysis. Thus, the electrocardiograms from HPT patients, compared to normocalcemic control patients, showed a shorter duration of the ST segment, representing the systolic interval, and an increased amplitude of the QRS complex, representing ventricular muscle mass. Furthermore, the duration of the T wave was significantly prolonged in HPT patients. The hemodynamic effects of these findings have to be further evaluated. PMID- 8201302 TI - Affective reactivity of language in stable schizophrenic outpatients and their parents. AB - We assessed levels of communication disturbance by counting the frequency of unclear linguistic references in the speech of 10 stable schizophrenic outpatients, 18 of their "unaffected" parents, and 10 nonpsychiatric controls, in affectively negative versus affectively positive conditions. Patient and parent groups scored approximately equally on the reference performance measure in the positive condition, and significantly more poorly than controls. Patients' speech deteriorated significantly in the negative condition, while parents' and controls' speech did not. The degree to which patients' speech was reactive to negative affect corresponded to the severity of their core positive symptoms of delusions and hallucinations. Poor reference performance in parents predicted poor performance and a more severe history of positive symptoms in their patient offspring. These data support the hypothesis that poor reference performance represents a vulnerability marker for schizophrenia, and that affective reactivity of language symptoms is associated with an underlying positive schizophrenic process. PMID- 8201303 TI - Patterns of speech disorders in schizophrenia and mania. AB - Formal thought disorder (FTD), defined as abnormal speech, has been associated with schizophrenia and likened to fluent aphasia. Whether FTD differentiates subtypes of schizophrenics and discriminates schizophrenics from other patients is unclear. We studied this issue by analyzing ratings of FTD of 170 schizophrenics and 62 manics. Eighty percent of emotionally blunted schizophrenics had FTD compared with 6.5% of manics. Factor analysis revealed verbiage disturbance and disorganized speech factors (44% of the variance). We assessed the discriminating ability of these factors, and compared these results to those from factors derived from Andreasen's positive/negative FTD construct, and to factors derived from speech and language diagnostic criteria for schizophrenia and mania in the proposed DSM-IV. Overall classifications were similar (91%, 91%, and 88%, respectively). We also found that FTD was related to emotional blunting, but not to other psychopathology. PMID- 8201304 TI - The mental health relevance of idioms of distress. Anger and perceptions of injustice among New York Puerto Ricans. AB - Cultural sensitivity in mental health research is enhanced by examining the collective perceptions of members of ethnic groups about their own idiomatic expressions of distress. Such an examination was conducted with Puerto Ricans living in New York City, beginning with focus group discussions. Their prevailing idioms of distress, based upon themes of anger and injustice, were correlated widely with professionally developed measures of anxiety, depression, and somatization and with utilization of professional mental health care. By examining the relationship between idioms of distress, saliently volunteered by members of the ethnic ingroup, on the one hand, and professional care and assessments of mental health, on the other, we increase our culturally based understanding of mental health in the community. PMID- 8201305 TI - Disease, disorder, or deception? Latah as habit in a Malay extended family. AB - Thirty-seven cases of latah are examined within the author's Malay extended family (N = 115). Based on ethnographic data collected and a literature review, cases are readily divisible into two broad categories: habitual (N = 33) and performance (N = 4). The first form represents an infrequent, culturally conditioned habit that is occasionally used as a learned coping strategy in the form of a cathartic stress response to sudden startle with limited secondary benefits (i.e., exhibiting brief verbal obscenity with impunity). In this sense, it is identical to Western swearing. Performers are engaged in conscious, ritualized social gain through the purported exploitation of a neurophysiological potential. The latter process is essentially irrelevant, akin to sneezing or yawning. It is concluded that latah is a social construction of Western-trained universalist scientists. The concept of malingering and fraud in anthropology is critically discussed. PMID- 8201306 TI - Remission and relapse of substance use disorders in schizophrenia. Results from a one-year prospective study. AB - Recent studies of the effectiveness of specialized programs that treat substance use disorders in schizophrenia have obtained promising results but have not involved control groups. Interpretation of these apparently positive results is problematic because remission and relapse rates of substance use disorders have not been reported in this population. The present study reports 1-year rates of substance abuse and dependence remission and relapse in a sample of schizophrenics taken from the Epidemiologic Catchment Area study. Results indicated that the prevalence of substance use disorders in schizophrenia remained constant over the year primarily because rates of remission were balanced by rates of relapse. Individuals who developed abuse or dependence over the year were younger, male, and showed increases in depression and risk for hospitalization over the year. Individuals who remitted abuse or dependence were older, female, and showed decreases in depression over the year. Dual diagnosis treatment programs have recently reported higher rates of remission than were evidenced in this sample, thus providing preliminary support for the effectiveness of these treatments. PMID- 8201307 TI - Substance abuse and bipolar affective disorder. AB - This interview study was conducted to explore the onset, course, and features of bipolar affective disorder complicated by substance abuse. Forty-four patients with a diagnosis of bipolar affective disorder were interviewed using the Structured Clinical Interview for DSM-III-R, Hamilton Rating Scale for Depression, Young Mania Rating Scale, and a questionnaire concerning psychiatric history. Current substance users averaged twice as many hospitalizations for mood problems. The age of onset of mood problems for substance users was significantly earlier than that of the nonusers (p < or = .05). Substance users were four times as likely to have other comorbid axis I disorders (p < or = .05) and twice as likely to have dysphoric mania at time of interview. This preliminary study suggests that individuals with bipolar affective disorder complicated by substance abuse may have more hospitalizations, a higher incidence of dysphoric mania, earlier onset of mood problems, and more comorbid axis I disorders. PMID- 8201308 TI - The acute effects of a rapid medical detoxification upon dysphoria and other psychopathology experienced by heroin abusers. AB - Self-reported dysphoria, personality disorder traits, and subjective opioid withdrawal symptoms were assessed in 30 opioid abusers before and after a rapid medical detoxification from heroin. Subject exclusion criteria reflected an effort to control for potential sources of affective change that were extraneous to the effect of detoxification. Subjects received few rehabilitative services during their 12-day inpatient hospitalization, and were not permitted visitors or off-ward privileges. At the preadmission assessment, they reported elevated levels of dysphoria and personality disorder traits, as well as opioid withdrawal symptoms. The results indicate that clinically significant declines in symptoms of dysphoria, opioid withdrawal symptoms, and personality disorder traits occur during the course of a rapid medical detoxification. Dysphoric and opioid withdrawal symptom abatement was most pronounced between the preadmission and admission assessments. These factors should be considered in the clinical diagnosis and treatment, as well as in research about psychiatric comorbidity of these substance abusers. PMID- 8201309 TI - 25th Meeting of the American Society for Neurochemistry. Albuquerque, New Mexico, March 5-9, 1994. Abstracts. PMID- 8201310 TI - New teleocidin-related metabolites, (-)-7-geranylindolactam V and blastmycetin F, from Streptoverticillium blastmyceticum. AB - Two new teleocidin-related metabolites, (-)-7-geranylindolactam-V [2] and blastmycetin F [3], were isolated from fermentation broths of the actinomycete Streptoverticillium blastmyceticum NA34-17, and their structures were determined by spectroscopic methods. Compound 2 bound strongly to phorbol ester receptors in a mouse epidermal particulate fraction, suggesting that it is a potent in vivo tumor promoter comparable to teleocidins A-1 [4] and B-4 [5]. PMID- 8201311 TI - Kneglomeratanol, kneglomeratanones A and B, and related bioactive compounds from Knema glomerata. AB - One new phenylalkyl phenol, kneglomeratanol [1], and two new acetophenones, kneglomeratanones A [2] and B [3], together with ten known compounds, 3-(12' phenyldodecyl)-phenol [4], 3-(10'-phenyldecyl)-phenol [5], 5-pentadecylresorcinol [6], 5-(10'-phenyldecyl)-resorcinol [7], 5-(12'-phenyldodecyl)-resorcinol [8], 2,4-dihydroxy-6-(10'-phenyldecyl)-acetophenone [9], 2-hydroxy-6-(12' phenyldodecyl)-benzoic acid [10], formononetin, biochanin A, and 8-O methylretusin, have been isolated from the stem bark of Knema glomerata. Brine shrimp lethality was used for the activity-directed chromatographic fractionations. All of these compounds showed moderate but significant toxicities to three human tumor cell lines and inhibited the growth of crown gall tumors on discs of potato tubers. PMID- 8201312 TI - Biosynthetic studies on the origin of the cyclohexanecarboxylic acid moiety of ansatrienin A and omega-cyclohexyl fatty acids. AB - Feeding experiments with [2,6,10,10-2H4]chorismate in Streptomyces collinus (ansatrienin A) and Alicyclobacillus acidocaldarius (omega-cyclohexyl fatty acids), and inhibitor experiments with glyphosate in the latter organism, have shown that the biosynthesis of cyclohexanecarboxylic acid branches off from the shikimate pathway at a point prior to enolpyruvylshikimate 3-phosphate, either at shikimate or shikimate 3-phosphate. PMID- 8201313 TI - Increased feline cerebral blood flow induced by dehydroevodiamine hydrochloride from Evodia rutaecarpa. AB - Dehydroevodiamine hydrochloride (0.1-0.3 mg/kg iv), which was isolated from the leaves of Evodia rutaecarpa, increased the cerebral blood flow recorded from the surface of the supra-sylvian gyrus in anesthetized cats. This action reached a maximum 1-4 min after injection and continued for 10 min. However, the compound had negligible effects on other cardiorespiratory functions at the doses examined. These results suggest that the compound selectively increases cerebral blood flow. PMID- 8201314 TI - An antifungal polyacetylenic compound from the culture filtrate of the fungus Trametes pubescens. PMID- 8201315 TI - Isolation of flavins from the Amazonian shrub Faramea guianesis. AB - In the pursuit of new leishmanicidal natural products, 5,7,4'-trihydroxyflavan [1] and the new product, 5,7-dihydroxy-4'-methoxyflavan [2], were isolated from the Guianian medicinal plant Faramea guianensis. PMID- 8201316 TI - beta-Carbolines from the blue-green alga Dichothrix baueriana. AB - Three new chlorine-containing beta-carbolines, bauerines A-C (1-3), have been isolted from the terrestrial blue-green alga Dichothrix baueriana GO-25-2, and identifying mass and nmr spectral analysis. The alkaloids show activity against herpes simplex virus type 2. PMID- 8201317 TI - Isolation and structure of harzianum A: a new trichothecene from Trichoderma harzianum. AB - A new trichothecene, harzianum A [1], was isolated from the soil-borne fungus Trichoderma harzianum. The structure of 1 was determined by extensive spectral analyses including the nmr techniques of PS-COSY, HMQC, HMBC, and NOESY. Harzianum A [1] contains a (Z,E,E)-2,4,6-octatriendioic acid esterified on the 4 beta hydroxyl group of trichodermol and is structurally related to the trichoverroids. Harzianum A [1] showed no cytotoxicity against baby hamster kidney cells, no activity against Gram-negative and Gram-positive bacteria, but modest antifungal activity at 100 micrograms/ml. PMID- 8201318 TI - Koumbalones A and B, new casbane diterpenes from Maprounea africana. AB - The organic extract of Maprounea africana yielded koumbalones A [1] and B [2], defined by spectral methods as new variations on the casbane ring system. The gross structures, relative configurations, and solution conformations were determined by a combination of spectral analyses and molecular modeling. Because koumbalone A spontaneously converts to koumbalone B at room temperature, koumbalone B may be an artifact of isolation. PMID- 8201319 TI - Archie Cochrane's challenge: can periodically updated reviews of all randomised controlled trials relevant to neurology and neurosurgery be produced? PMID- 8201320 TI - Rene Theophile Hyacinthe Laennec (1781-1826). PMID- 8201321 TI - Stroke and transient ischaemic attacks. PMID- 8201322 TI - Carbohydrate-deficient glycoprotein syndrome: clinical expression in adults with a new metabolic disease. AB - A new group of recessively inherited metabolic disorders affecting glycoprotein metabolism has been identified--the carbohydrate-deficient-glycoprotein (CDG) syndromes. Here the course and clinical expression of CDG syndrome type I in 13 patients who have passed the age of 15 years are described. All presented with early onset psychomotor retardation, in most cases combined with slight facial dysmorphic features, some degree of hepatic dysfunction, and in one case, pericardial effusion. About half of the patients had subcutaneous lipodystrophy and comatose or stroke-like episodes during childhood. After the age of 15 the disease was mainly characterised by neurological symptoms consisting of non progressive ataxia associated with cerebellar hypoplasia, stable mental retardation, variable peripheral neuropathy, and strabismus. One third of the patients had generalised seizures, usually sporadic, and all had retinal pigmentary degeneration. In all cases there was more or less pronounced thoracic deformity and no female had passed puberty. Also, the oldest female showed premature aging. Severe internal organ symptoms, which are common in pediatric patients, were absent. All patients had highly raised serum concentrations of the biochemical marker carbohydrate-deficient transferrin, which can be used to verify the diagnosis. It is concluded that after childhood, CDG syndrome type I is a largely non-progressive disease compatible with a socially functioning but dependent lifestyle. PMID- 8201323 TI - Platelet secretion from dense and alpha-granules in vitro in migraine with or without aura. AB - Several studies in vivo indicate platelet activation in migraine, as reflected by increased plasma concentrations of platelet secretory products. In vitro data on platelet secretion are scant, which prompted an investigation into agonist induced platelet aggregation and secretion in platelets from patients with migraine. Sixty two patients with migraine with aura (MA) and 41 with migraine without aura (MwA) were studied during a headache-free phase, together with 26 healthy controls. Platelet aggregation and secretion in platelet-rich plasma were induced by collagen and platelet activating factor (PAF). Serotonin was measured by high performance liquid chromatography and platelet factor 4 (PF4) with an enzyme immunoassay kit. There were no significant aberrations in platelet aggregation in those with migraine compared with healthy controls. The platelet PF4 secretion induced by PAF (1.0 and 0.1 microM) was increased in MwA (p < 0.05, p < 0.0001) compared with controls, and there was a similar trend in MA (NS, p < 0.01). By contrast, the PF4 secretion induced by collagen (0.5 and 2.0 micrograms/ml) was reduced in MA (p < 0.01 and p < 0.05). Further, the MA group exhibited increased basal intraplatelet serotonin concentrations (p < 0.0001) and increased serotonin secretion induced by both concentrations of collagen (p < 0.0001) and PAF (p < 0.001). The data indicate an abnormal platelet a-granule secretion in those with migraine, and focus attention on PAF as a possible factor contributing to the platelet activation associated with migraine. The increased platelet content and secretion of serotonin was specific to MA, and may reflect different serotonin turnover in the two clinical migraine types. PMID- 8201324 TI - Motor response to apomorphine and levodopa in asymmetric Parkinson's disease. AB - The motor responses of 14 patients with Parkinson's disease (six previously untreated and eight chronically receiving levodopa) with pronounced asymmetry in the severity of motor signs between the left and right sides of the body were studied. The effects of a short (60 minutes) and a long (16-22 hours) intravenous levodopa infusion as well as of subcutaneous apomorphine (1-6 mg bolus) were assessed. Four different tapping tests were used to measure motor function. For all pharmacological tests, the more affected side showed a shorter response duration, increased latency, and greater response magnitude than the less affected side. These differences were more pronounced in those patients receiving chronic levodopa treatment. As apomorphine is not dependent on dopamine storage capacity, these findings suggest that postsynaptic mechanisms play an important part in the origin of motor fluctuations in Parkinson's disease. PMID- 8201325 TI - Normal activation of the supplementary motor area in patients with Parkinson's disease undergoing long-term treatment with levodopa. AB - Regional cerebral blood flow (rCBF) changes in cortical motor areas were measured during a movement of the dominant right hand in 15 patients with Parkinson's disease deprived of their usual levodopa treatment, in 11 patients with Parkinson's disease undergoing long-term treatment with levodopa, and in 15 normal volunteers. The supplementary motor areas were significantly activated in the normal subjects and in the patients receiving levodopa but not in the patients deprived of levodopa. The contralateral primary sensory motor area was significantly activated in all three groups. The ipsilateral primary sensory motor cortex was not activated in the normal subjects and the non-treated patients but was in the patients treated with levodopa. It is concluded that the supplementary motor area hypoactivation which is observed in akinetic non-treated patients with Parkinson's disease is not present in patients undergoing long-term treatment with levodopa. This result suggests that (a) levodopa improves the functional activity of supplementary motor areas in Parkinson's disease and (b) there is no pharmacological tolerance to this effect. The ipsilateral primary motor cortex activation observed in the patients treated with levodopa could be related to levodopa-induced abnormal involuntary movements. PMID- 8201326 TI - Peripheral and central conduction studies in neurolathyrism. AB - To study the involvement of motor and sensory pathways in neurolathyrism, 19 patients with lathyrism from Unnao, India, where lathyrism is endemic, were studied. The mean age of the patients at the time of the onset of illness was 35.8 (range 18-70) years. The mean duration of illness was 15.6 (range 2-30) years. The clinical picture comprised walking difficulty due to stiffness and mild weakness in all 19 patients, cramps in the legs in five, frequency or urgency of micturition in five, and flexor spasms in three. There was pronounced leg spasticity with a mean Ashworth score of 4.1 (range 2.9-5). Central motor conduction to the tibialis anterior muscle (CMCT-TA) was slow in 14 of the 17 patients (21 sides). Slowing of peripheral motor nerve conduction, although less pronounced, was significant in the upper limb in four and the lower limb in seven sides. The tibial somatosensory evoked potentials were normal and peroneal nerve conduction was marginally impaired. Values for CMCT-TA correlated with the degree of spasticity (p < 0.02) whereas weakness, crossed adductor reflexes, and clonus did not. The wide variability of CMCT-TA in lathyrism may be due to involvement of different types of fibres. Large diameter fibre involvement may cause pronounced slowing. Small diameter fibre involvement could produce appreciable spasticity and mild weakness but a lesser degree of slowing or even normal conduction. PMID- 8201327 TI - Immunoadsorption therapy for myasthenia gravis. AB - The results of a multicentre trial were analysed to evaluate the efficacy of immunoadsorption therapy for severe generalised myasthenia gravis. Twenty patients with myasthenia gravis who were concurrently receiving high dose prednisolone and azathioprine therapy were treated with an affinity-type adsorbent, using tryptophan-linked polyvinyl alcohol gel (IM-TR), according to a standardised treatment protocol. The 20 patients received five adsorption treatments within a period of 10 days. In 11, pronounced improvement of myasthenic weakness was seen and long-term remission was maintained. The treatment was especially effective in patients with thymic hyperplasia. Circulating acetylcholine receptor (AChR) antibodies were reduced by about 60% by treating one plasma volume. There was no difference in the rate of removal of the AChR antibodies between patients with thymic hyperplasia and patients with thymoma. No serious complications occurred during 100 procedures. It was concluded that the immunoadsorption therapy with IM-TR is useful in controlling symptoms in patients with severe myasthenia gravis who are otherwise unresponsive. PMID- 8201328 TI - Management of severe spasticity with intrathecal baclofen delivered by a manually operated pump. AB - Intrathecal baclofen abolishes spasticity in many patients with neurological diseases but there are few studies on its long-term effectiveness. Since 1986 a manually operated subcutaneous pump has been used to deliver baclofen intrathecally in 21 patients with a follow up of at least one year. Most patients had multiple sclerosis and all were wheelchair-bound. Sixteen patients had a complete and sustained benefit. In four other patients the treatment was effective in the short term but not in the long term. In the remaining patient the pump never worked. Complications included meningitis, pump failure, erosion through the skin, and baclofen overdose. Nevertheless, only three patients have asked to discontinue the treatment. We conclude that intrathecal baclofen, delivered by a manually operated implanted pump, is an effective treatment for severe spasticity in most patients. PMID- 8201329 TI - MELAS syndrome with mitochondrial tRNA(Leu(UUR)) gene mutation in a Chinese family. AB - The clinical features of a patient in a Chinese family with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) are reported. The study revealed that hearing and visual impairments and miscarriages may be early clinical presentations in MELAS. A heteroplasmic A to G transition in the tRNA(Leu(UUR)) gene was noted at the nucleotide pair 3243 in the mitochondrial DNA of muscle, blood, and hair follicles of the proband and his maternal relatives. Quantitative analysis of the mutated mitochondrial DNA revealed variable proportions in different tissues and subjects of maternal lineage in the family. Muscle tissue contained a higher proportion of the mutant mitochondria than other tissues examined. The function of the reproductive system of the proband seems to be impaired. In one clinically healthy sibling, the 3243rd point mutation was found in sperm mitochondrial DNA, although sperm motility was not affected. It seems that biochemical defects in mitochondrial respiration and oxidative phosphorylation are tissue specific expressions of the 3243rd point mutation in the mitochondrial DNA of the affected target tissues. PMID- 8201331 TI - Diffuse neurofibrillary tangles with calcification: a new presenile dementia. AB - The term "diffuse neurofibrillary tangles with calcification" (DNTC) is proposed for a new form of presenile dementia. It is characterised by slowly progressive cortical dementia in the presenium, localised temporal or temporofrontal lobar atrophy, numerous neurofibrillary tangles widespread in the cerebral cortex, and pronounced calcareous deposits; 16 cases of DNTC, have been reported. PMID- 8201330 TI - Hippocampal atrophy correlates with severe cognitive impairment in elderly patients with suspected normal pressure hydrocephalus. AB - Measurements of hippocampal formation atrophy using MRI have been useful in distinguishing demented patients with a diagnosis of probable Alzheimer's disease from cognitively normal controls. To determine whether there is a similar relationship between hippocampal size and dementia in elderly patients suspected of normal pressure hydrocephalus (NPH), the authors obtained mini-mental status examination (MMSE) scores and MRI measurements of hippocampal size and CSF volume on 16 elderly patients whose severe ventriculomegaly and unexplained gait impairment made NPH a probable diagnosis. Hippocampal size correlated strongly with MMSE score (r = 0.75, p < 0.001); no significant MMSE correlation was found for ventricular CSF volume or extra-ventricular/ventricular CSF ratio. It was concluded that hippocampal atrophy is associated with severe cognitive dysfunction in many elderly patients with a diagnosis of NPH. As a hypothesis for further investigation, the detection of such atrophy may help identify cases where the presence of a pathology of Alzheimer's disease complicates the diagnosis of NPH. PMID- 8201333 TI - Semantic memory and frontal executive function during transient global amnesia. AB - To assess semantic memory and frontal executive function, two patients underwent neuropsychological testing during transient global amnesia (TGA) and after an interval of 6-8 weeks. In spite of a profound deficit in anterograde verbal and non-verbal memory, semantic memory was normal, as judged by category fluency measures, picture naming, and picture-word and picture-picture matching, and reading ability was normal. Similarly, there were no deficits on a number of tests known to be sensitive to frontal executive dysfunction. A hexamethylpropyleneamine-oxime (HMPAO) single photon emission CT (SPECT) scan, obtained on one patient 24 hours post-TGA, showed focal left temporal lobe hypoperfusion which had resolved three months later. The observed dissociation between episodic and semantic memory is discussed in the light of contemporary cognitive theories of memory organisation. PMID- 8201332 TI - Residual rightward attentional bias after apparent recovery from right hemisphere damage: implications for a multicomponent model of neglect. AB - Unilateral neglect may be a multicomponent attentional disorder consisting of an initial automatic orienting of attention toward the ipsilesional side and a subsequent impairment in contralesionally reorienting attention, both of which are superimposed on a generalised reduction in attention resources. It has been hypothesised that patients' ability to reorient attention contralesionally may recover relatively quickly, but that the ipsilesional attention bias may be relatively persistent. This hypothesis was tested by consecutively examining 13 patients who had had a right hemisphere stroke, and who had left unilateral neglect. They were examined once shortly after the stroke and again 12 months later, using a battery of standard clinical and experimental tasks. Patients initially showed a strong and consistent rightward attentional bias in addition to a failure to reorient their attention leftward. After 12 months patients continued to show an abnormal ipsilesional attentional bias, though most were now able to fully reorient their attention toward the contralesional side. These results suggest that restitution of the capacity to reorient attention contralesionally may underlie the apparent recovery from clinical signs of unilateral neglect. The presence of a residual ipsilesional attentional bias in most patients, however, may, at least in part, account for the poor functional outcomes in some apparently "recovered" patients. PMID- 8201334 TI - Naming difficulties in alexia with agraphia for kanji after a left posterior inferior temporal lesion. AB - The case is described of a patient with alexia and agraphia for kanji, and severe anomia after a subcortical haemorrhage in the left posterior inferior temporal area. Magnetic resonance imaging at four months after onset showed a lesion in the inferior temporal and fusiform gyri, extending from the temporo-occipital junction toward the anterior third of the temporal lobe. Comparison with other reported cases of alexia with agraphia and anomia made it clear that when accompanied by severe anomia, the lesions extended either forward to the anterior part of the middle temporal gyrus or medially to the parahippocampal gyrus. It is suggested that the disconnection of association fibres between the parahippocampal, fusiform, middle, and inferior temporal gyri, especially between the parahippocampal gyrus and the other temporal gyri, or the cortical damage to the posterior part of these gyri is essential for the production of anomia. PMID- 8201335 TI - Neuropsychological findings in a non-clinical sample of workers exposed to solvents. AB - The risk of long-term damage to the CNS after exposure to mixed solvents in work environments is controversial. Thirty-six workers were studied who had been exposed to organic solvents for more than 10 years (mean 24.5 years) in a working environment. The workers and unexposed controls were studied with a battery of neuropsychological and cognitive tests. Significant group differences were observed for the Wechsler adult intelligence scale (WAIS) digit span and symbol digit substitution, and on paired associate learning and continuous word recognition. The results suggest that long-term work-related exposure to organic solvents may have chronic toxic effects. PMID- 8201336 TI - Chronic fatigue syndrome: a follow up study. AB - Forty-six of 47 patients diagnosed as having chronic fatigue and offered treatment four years previously were followed up. Twenty-nine patients were interviewed, three patients refused an interview, and information on the remaining 14 was obtained from their general practitioners. All the instruments used at interview had been used in the initial study. The long-term prognosis for patients with chronic fatigue syndrome who have initially responded to treatment is good. Spontaneous recovery in those who declined or who did not benefit from treatment is unlikely. Patients who continue to fulfil the criteria for chronic fatigue syndrome four years after they were initially diagnosed are likely to have had more somatic disorders, to have been more fatigued, and to have had a previous psychiatric history when they were initially assessed. PMID- 8201337 TI - Are brief or recurrent transient global amnesias of epileptic origin? AB - To evaluate if short (less than one hour) or recurrent, or both, episodes of transient global amnesia (TGA) have an epileptic origin or carry a subsequent risk of epilepsy a group of patients with these types of TGA attacks was studied. The group was selected from a prospective series of 103 patients with TGA. Sixteen patients had an episode lasting less than one hour, 13 had more than one episode, and five patients had both short and recurrent attacks. For each patient the number of recurrences was small (four or less) and they were separated by months or years. During short attacks of TGA many subjects showed other typical features of TGA including repeated questioning (12 subjects) and performance of purposeful complex acts (eight subjects). Twelve short attacks were closely related to a characteristic precipitating event. During follow up only one patient had a seizure (partial motor). No other association between either short or repeated attacks of TGA and past history of epilepsy or paroxysmal discharges were seen on the EEG. Short or recurrent, or both, attacks of TGA are not epileptic and do not carry a relevant risk of subsequent seizures. PMID- 8201338 TI - Nicolaus Petreus Tulpius (1593-1674) on headaches. PMID- 8201339 TI - Daytime sleep in myotonic dystrophy is not caused by sleep apnoea. AB - Daytime sleepiness is common in myotonic dystrophy and might be attributed to disturbed nocturnal breathing. Seventeen out of 22 patients complained of excessive daytime sleepiness, resembling "idiopathic hypersomnolence". Sleep apnoea might have contributed to daytime sleepiness in only three of 17 patients. Treatment with the central stimulant methylphenidate produced sustained benefit in seven out of 11 patients tested. Daytime sleepiness in myotonic dystrophy is usually caused by dysfunction of central sleep regulation and not by disturbed nocturnal breathing. PMID- 8201341 TI - Epilepsy. PMID- 8201340 TI - Infarction of the unilateral posterior horn and lateral column of the spinal cord with sparing of posterior columns: demonstration by MRI. AB - Infarction of the spinal cord, particularly in the distribution of the posterior spinal arteries, is rare. Twenty seven cases of posterior spinal artery syndrome have been reported. In all cases, the posterior columns were affected, and in all but two, the lesions were bilateral. Here a 49-year-old woman is reported, who was affected with lumbar cord infarction in the distribution of the posterior spinal arteries, diagnosed by MRI and clinical presentation. This case is of special interest because of sparing of the posterior columns and the unilateral nature of the lesion, even though the infarction occurred in the distribution of the posterior spinal arteries. PMID- 8201342 TI - Surface EMG and muscle fibre conduction during attacks of hypokalaemic periodic paralysis. AB - Surface EMG, muscle fibre conduction velocity (MFCV), muscle force, and biochemical variables were investigated in a 13-year-old boy with familial hypokalaemic periodic paralysis during and after three attacks of paralysis. After normalisation of the serum potassium values, strength rapidly returned to interictal values, but the integrated EMG and to a lesser extent the MFCV recovered more slowly. These findings suggest that a complete electrophysiological recovery is not necessary for a restoration of muscle force and that the pathogenetic defect is localised in the muscle membrane. PMID- 8201344 TI - Bontius and Tulp on beriberi polyneuropathy. PMID- 8201343 TI - Idiopathic AA amyloidosis manifested by autonomic neuropathy, vestibulocochleopathy, and lattice corneal dystrophy. AB - A 69-year-old Japanese woman with non-familial amyloidosis had polyneuropathy and profound autonomic neuropathy, and kappa chain monoclonal gammopathy. Immunohistopathological examination showed protein AA and protein AP in the amyloid deposits. She showed involvement of the vestibulocochlear nerve and lattice dystrophy of the cornea. Vestibulocochleopathy and corneal lattice dystrophy have been reported in familial amyloid polyneuropathy type IV, Finnish type, but never in non-familial amyloidosis. PMID- 8201345 TI - Anticentriolar autoantibodies in children with central nervous system manifestations of Mycoplasma pneumoniae infection. AB - Serum samples from 49 children with acute Mycoplasma pneumoniae infection were screened for the presence of antibodies to mitotic spindle apparatus. None of these serum samples showed such antibodies at a screening dilution of 1:40, though anticentriolar antibodies at titres of 1:320 were observed in two children with acute cerebellar dysfunction. Anticentriolar antibodies may play a part in the pathogenesis of CNS disease associated with M pneumoniae infection. PMID- 8201346 TI - Benign neurogenic amyotrophy in Klinefelter's syndrome. AB - Two cases of benign neurogenic amyotrophy associated with Klinefelter's syndrome are reported. Both presented with slowly progressive, diffuse neurogenic muscle atrophy of juvenile onset. Both had a karyotype of XXY. Amplification, by the polymerase chain reaction, of a fragment of androgen receptor that was related to bulbospinal muscular atrophy, showed no abnormality. Treatment with androgen in one case provided no benefit. Benign neurogenic amyotrophy in the Klinefelter's syndrome is likely to be an independent type of motor neuron disease and suggests that the X chromosome plays an important part in the biology of motor neurons. PMID- 8201347 TI - Amnesic syndrome after theophylline associated seizures: iatrogenic brain injury. AB - Two patients developed a disabling amnesic syndrome after seizures associated with oral theophylline treatment. Such seizures are more likely in the elderly, in the presence of pre-existing neurological disease, and when theophylline is given with certain antibiotics and cimetidine. The mechanism of neuronal injury may be by the excessive release of endogenous excitotoxic glutamate. PMID- 8201348 TI - Haemorrhage associated with silastic dural substitute. AB - Three cases of haemorrhage after the use of a silastic dural substitute are presented. In all cases the implant was removed and further haemorrhage has not occurred. Published work is reviewed and the implications for the continued use of silastic are discussed. PMID- 8201349 TI - John and James Parkinson on appendicitis. PMID- 8201350 TI - Alphabetical paragraphia in a limited middle cerebral artery stroke. AB - A Yugoslavian perfectly bilingual for French and Serb had a limited left middle cerebral artery stroke. He developed a peculiar dysgraphia characterised by the use of Latin characters (French spelling) to transcribe Serb phonemes that would normally have been spelt in the Cyrillic alphabet. This dysgraphia was likely to be due to an impairment of the allographic procedure. It is concluded that allographs of the two alphabets are produced concomitantly in bialphabetical patients during the allographic procedure. PMID- 8201351 TI - Impaired stereoacuity due to a lesion in the left pulvinar. AB - A right-handed patient with a haematoma in the left pulvinar showed impaired stereoacuity. In contrast with previous reports, he did not show peripheral visual extinction or prolonged reaction times for targets on the side contralateral to the lesion. PMID- 8201352 TI - Congenital protein C deficiency and superior sagittal sinus thrombosis causing isolated intracranial hypertension. AB - The first case of a superior sagittal sinus thrombosis causing isolated intracranial hypertension as a result of congenital protein C deficiency is reported. Such a possibility must not be overlooked. Anticoagulation is recommended as a treatment for cerebral venous thrombosis. In the case of congenital protein C deficiency, vitamin K antagonists must be started cautiously due to the risk of skin necrosis. PMID- 8201353 TI - Dystonia-parkinsonism syndrome resulting from a bullet injury in the midbrain. PMID- 8201354 TI - Direct evidence for limited clonality of antibodies to glutamic acid decarboxylase (GAD) in stiff man syndrome using baculovirus expressed GAD. PMID- 8201355 TI - The use of botulinum toxin to treat "striatal" toes. PMID- 8201356 TI - Non-ischaemic causes of transient ischaemic attacks and minor strokes. PMID- 8201357 TI - Sumatriptan and giant cell arteritis. PMID- 8201358 TI - Isolated lingual myoclonus associated with an Arnold-Chiari malformation. PMID- 8201359 TI - Ankylosing spondylitis associated with myositis. PMID- 8201360 TI - Incorrect diagnosis of myotonic dystrophy and its potential consequences revealed by subsequent direct genetic analysis. PMID- 8201361 TI - Lactate responses to exercise in chronic fatigue syndrome. PMID- 8201362 TI - PET assessment of brain metabolic recovery in aphasia. PMID- 8201363 TI - Functional integrity of the structural unaffected left hemisphere in crossed aphasia. PMID- 8201364 TI - Lactation education practice and procedure: information and support offered to economically disadvantaged women. AB - Seventy-five agencies providing services to a large percentage of economically disadvantaged pregnant women returned mailed survey questionnaires. These surveys described the timing and nature of lactation education available to clients of the respondent agencies. Lactation education was most frequently introduced at 16 week gestation. Fifty-seven (76%) of the respondents stated that lactation education was offered to all clients at least once during pregnancy, and 23 (31%) stated that all prenatal clients were expected to attend breastfeeding classes, regardless of stated feeding choice. Respondents generally agreed that breastfeeding should be encouraged if a woman is undecided about feeding issues, but they were less definite concerning active encouragement of breastfeeding to women who had made another feeding choice. These findings may facilitate the effort to increase initiation of breastfeeding by examining education practices and provider attitudes that may foster or hinder breastfeeding adoption in this client population. PMID- 8201365 TI - Perceived social support and social network of low-income mothers of infants and preschoolers: pre- and postparenting program. PMID- 8201366 TI - A collaborative endeavor: the Southeast Florida Public Health Nursing Education and Service Consortium. PMID- 8201367 TI - Respite for caregivers: an evaluation study. AB - This evaluation study measured the effect of respite on family caregivers of the elderly. The specific aims were: (a) to learn the effect of respite on the evaluation variables of caregiver quality of life, mood, and response to caregiving; (b) to learn relations between the demographic variables and the evaluation variables; and (c) to examine respite to identify benefits other than those being directly measured. Subjects were 130 caregivers, with 6- and 12-month data on a small subsample of the 130. Interviews with caregivers and satisfaction surveys supported respite as an effective intervention. Quantitative analysis showed that none of the evaluation variables changed statistically. The caregiver mood variable evidenced positive changes; other variables changed negatively. Research issues, such as the short time subjects were in the respite program and the lack of sensitive measurement tools, are discussed. Clinical implications for community health nurses are also discussed. PMID- 8201368 TI - New concepts in nursing management of the TB patient: a community training program. AB - This article describes the development and implementation of interventions aimed at improving return rates for reading of Mantoux tuberculosis (TB) injections and subsequent referrals. The TB screening program, sponsored by a midwestern Native American primary health care service, was initiated in response to an identified Native-American TB case. The return rate of 61% was considered unsatisfactory, and a program training 20 community health care, alcohol and substance, and social-service workers to read TB tests after screening by a community health nurse was implemented. Implementation of an interagency agreement developed to improve referral completion rates is described. PMID- 8201369 TI - Nursing diagnosis in home care: audit tool development. AB - Little research has been done to document the value of using nursing diagnosis in home care and the impact that increased acuity levels have had in diagnostic selection. Nursing diagnosis documentation in home care was examined to see whether it had a relation to select client and visit pattern variables. This retrospective chart audit, which piloted a newly developed instrument called the Home Care Audit Tool, utilized a sample of 199 closed records of a large midwestern Visiting Nurse Association. The mean age of the client population was 76 years, with 64% female. There were 269 initial nursing diagnoses cited in the sample records, averaging 1.75 diagnoses per case. The number of recorded visits increased when select nursing diagnoses were cited together in a single case. PMID- 8201370 TI - Three stakes in hydrazine sulfate's heart, but questionable cancer remedies, like vampires, always rise again. PMID- 8201371 TI - AIDS-related Kaposi's sarcoma: still a problem, still an opportunity. PMID- 8201372 TI - Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: a randomized placebo-controlled, double-blind phase III study of the Cancer and Leukemia Group B. AB - PURPOSE: To assess the chemotherapy regimen of cisplatin, vinblastine, and hydrazine sulfate administered to patients with non-small-cell lung cancer (NSCLC) in a randomized, placebo-controlled double-blind phase III study. PATIENTS AND METHODS: Between July 25, 1989 and February 1, 1991, 291 patients with stage IIIB or IV NSCLC and performance status 0 or 1 were randomized to receive cisplatin 100 mg/m2 intravenously (IV) every 28 days, vinblastine 5 mg/m2 IV per week times five, then every 2 weeks; and either hydrazine sulfate 60 mg three times per day orally or placebo. The concurrent use of corticosteroids, medroxyprogesterone, or other appetite stimulants was not permitted. Treatment groups were comparable for known prognostic variables. The primary end point of this study was survival; however, the influence of hydrazine sulfate on nutritional status, performance status, and quality of life was also assessed. RESULTS: Analysis of 266 eligible patients showed a median survival duration of 7.78 months for the hydrazine sulfate-treated group compared with 7.70 months for the placebo-treated group (P = .65, log-rank). Objective response rates were similar for the two groups, with 4% complete responses, 20% partial responses, and 2% regressions in those treated with hydrazine sulfate; 3% complete responses, 23% partial responses, and 2% regressions in those who received placebo. The major toxicity was severe or life-threatening neutropenia, which occurred in 65% of hydrazine sulfate patients and 63% of placebo patients. There were no differences noted between the two groups in degree of anorexia, weight gain or loss, or overall nutritional status. Sensory and motor neuropathy occurred significantly more often in patients treated with hydrazine sulfate. Quality of life was significantly worse in patients who received hydrazine sulfate. CONCLUSION: This study suggests no benefit from the addition of hydrazine sulfate to an effective cytotoxic regimen. PMID- 8201373 TI - Randomized placebo-controlled evaluation of hydrazine sulfate in patients with advanced colorectal cancer. AB - PURPOSE: Hydrazine sulfate is a controversial agent that was originally studied in cancer patients approximately 20 years ago. Based on a series of recent trials that suggested that this drug might have utility in cancer patients, we conducted this study. PATIENTS AND METHODS: Patients with metastatic colorectal cancer were randomized to receive hydrazine sulfate or placebo in a double-blinded manner. Protocol patients did not concurrently receive any other systemic antineoplastic treatment. RESULTS: There were 127 assessable patients entered onto this clinical trial. Data from the study showed trends both for poorer survival and for poorer quality of life (QL) in the hydrazine group. There were no significant differences in the two study arms with regard to anorexia or weight loss. CONCLUSION: This trial failed to demonstrate any benefit for hydrazine sulfate. PMID- 8201374 TI - Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer. AB - PURPOSE: Hydrazine sulfate, an agent that appears to inhibit gluconeogenesis, has been studied in cancer patients for approximately 20 years. There was a recent resurgence of interest in this drug when subset analysis of a small placebo controlled, double-blind, clinical trial reported improved survival among non small-cell lung cancer patients with a good performance status who were randomized to receive this drug along with standard chemotherapy. PATIENTS AND METHODS: Patients on this trial had newly diagnosed, unresectable non-small-cell lung cancer and were treated with cisplatin and etoposide. In addition, they were randomized to receive hydrazine sulfate or placebo in a double-blind manner. RESULTS: A total of 243 patients were randomized. Response rates were similar in the two treatment arms. There were trends for worse time to progression and survival in the hydrazine sulfate arm. No significant differences were noted in the two study arms with regard to toxicity or quality of life (QL). CONCLUSION: This trial failed to demonstrate any benefit for patients who received hydrazine sulfate. PMID- 8201375 TI - Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma--reduced local recurrence but no improvement in survival: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. AB - PURPOSE: To evaluate the benefit of adjuvant chemotherapy in adult patients with soft tissue sarcomas. The principal end points were freedom from local recurrence and/or metastases and overall survival. PATIENTS AND METHODS: Between January 1977 and June 1988, 468 patients entered this randomized study and 317 were considered eligible. Following complete surgical resection with or without radiotherapy, outcome in 145 eligible patients receiving cyclophosphamide 500 mg/m2 intravenously (IV) bolus on day 1, vincristine 1.4 mg/m2 IV bolus on day 1, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) 50 mg/m2 IV bolus on day 1, and dacarbazine (DTIC) 400 mg/m2 by 1-hour infusion on days 1 to 3 (CYVADIC) cycles repeated every 28 days for eight courses was compared with that in 172 control patients. RESULTS: With a median follow-up duration of 80 months (range, 39 to 165), actuarial percentage survival figures at 7 years were compared. Relapse-free survival rates were higher for CYVADIC, 56% versus 43% (P = .007), and local recurrence was significantly reduced in the CYVADIC arm at 17% versus 31% (P = .004). In contrast, distant metastases occurred with similar frequency in both arms, 32% for CYVADIC versus 36% for control patients (P = .42), and overall survival rates were not significantly different at 63% versus 56% (P = .64). A reduction in local recurrence was only apparent in the group of head, neck, and trunk sarcomas (P = .002), but not in limb tumors (P = .31). CONCLUSION: Adjuvant chemotherapy with CYVADIC cannot be recommended outside the context of a clinical trial. Experience from this study has been used to plan a trial of neoadjuvant chemotherapy with doxorubicin/ifosfamide, which is currently in progress. PMID- 8201376 TI - A prospective randomized trial of adjuvant brachytherapy in the management of low grade soft tissue sarcomas of the extremity and superficial trunk. AB - PURPOSE: This study was designed to evaluate the impact of adjuvant brachytherapy (BRT) on local and systemic recurrence rates in patients with low-grade sarcoma. PATIENTS AND METHODS: Forty-five patients with histologic low-grade, completely resected soft tissue sarcomas of the extremity or superficial trunk were entered onto this trial. Following resection of all gross disease, patients were randomized to the BRT arm (n = 22) or to the no-BRT arm (n = 23). On the fifth or sixth postoperative day, catheters were loaded with iridium 192 to deliver a dose of 45 Gy to the tumor bed over 4 to 6 days. RESULTS: The two groups were evenly distributed with respect to the distribution of presentation status (primary v recurrent), tumor site (trunk v extremity, proximal v distal extremity), tumor size (< 5 cm v > or = 5 cm), tumor depth (superficial v deep), and microscopic tumor margins (positive v negative). The predominant histopathologic diagnosis in each group was liposarcoma (BRT, 13 of 22 [59%]; no BRT, 14 of 23 [61%]) with other histopathologic subtypes evenly distributed between the two groups. The median follow-up duration among the ongoing survivors is 67 months. One patient in the BRT group developed systemic disease and died of progressive disease. Local recurrence occurred in five of 23 patients (22%) in the no-BRT group and six of 22 patients (27%) in the BRT group (P = .60). CONCLUSION: Adjuvant radiation in the form of BRT does not appear to decrease local recurrence rates following complete resection of low-grade extremity and superficial trunk soft tissue sarcomas. Other adjuvant approaches, such as external-beam radiotherapy, are required to have a significant impact on local recurrence rates in this group of patients. PMID- 8201377 TI - A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma. AB - PURPOSE: This study investigated the feasibility of a novel approach to the treatment of malignant pleural mesothelioma by combining surgical resection with immediate postoperative intrapleural chemotherapy and subsequent systemic chemotherapy. PATIENTS AND METHODS: Patients with biopsy-proven, resectable malignant pleural mesothelioma underwent pleurectomy/decortication immediately followed by intrapleural chemotherapy with cisplatin 100 mg/m2 and mitomycin 8 mg/m2. Systemic chemotherapy was started 3 to 5 weeks postoperatively and included cisplatin 50 mg/m2 on days 1, 8, 15, 22, 36, 43, 50, and 57, and mitomycin 8 mg/m2 on days 1 and 36. Patients were then monitored by serial chest and abdominal computed tomographic (CT) scans every 3 months until death or for a minimum of 18 months, whichever occurred first. RESULTS: Of 36 patients entered onto the study, 28 had pleurectomy/decortication and intrapleural chemotherapy. There was one postoperative death, and two episodes of grade 4 renal toxicity after intrapleural chemotherapy. The 23 patients who also had systemic chemotherapy received a median of 80% and 87% of the planned total cisplatin and mitomycin doses, respectively. No grade 3 or 4 toxicities were observed. The overall survival rate of the 27 patients who were originally candidates for systemic chemotherapy was 68% at 1 year and 40% at 2 years, with a median survival duration of 17 months. Locoregional disease was the most common form of relapse (16 of 20 patients). CONCLUSION: This short but aggressive combined modality regimen was generally well tolerated, but should not be used outside of a protocol setting because of the potential for serious toxicity. Overall survival was as good or better than with previously reported multimodality approaches, but other strategies are needed to improve local control. PMID- 8201378 TI - Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group. AB - PURPOSE: The purpose of this study was to evaluate the impact of cisplatin, doxorubicin, and cyclophosphamide (PAC) in patients with advanced thymoma with respect to response rate, duration of remission, and overall survival. PATIENTS AND METHODS: Assessable patients with thymoma (n = 29) or thymic carcinoma (n = 1) with metastatic or locally progressive recurrent disease following radiotherapy were treated with intravenous cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) with normal saline hydration. Courses were repeated every 3 weeks for a maximum of eight cycles of therapy. RESULTS: Toxicity, which was primarily hematologic, was mild, with only one patient developing a fever associated with neutropenia. Three complete responses (CRs) and 12 partial responses (PRs) were observed (CR+PR rate, 50%; 95% confidence interval, 31.3% to 68.7%). Ten patients had stable disease. The median duration of response was 11.8 months (range, 0.9 to 70.5+), the time to treatment failure 18.4 months (range, 0.8 to 91.9+), and median survival time 37.7 months (range, 2 to 91.9+). CONCLUSION: This trial demonstrates that objective response rates and prolonged survival can be achieved in patients with advanced thymoma. PMID- 8201379 TI - ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. AB - PURPOSE: This study attempted to determine the efficacy of the combination of etoposide (VP-16), methyl-prednisolone, and cytarabine (Ara-C) with or without cisplatin in relapsing and refractory adult lymphoma patients. PATIENTS AND METHODS: The first 63 patients were randomized to receive VP-16 40 mg/m2/d for 4 days, methylprednisolone 500 mg intravenously daily for 5 days, and Ara-C 2 g/m2 intravenously over 2 to 3 hours on day 5 with or without cisplatin 25 mg/m2 IV administered by 24-hour infusion for 4 days (ESHA +/- P). Markedly different responses between ESHA (33%) and ESHAP (75%) led to deletion of the ESHA arm. A total of 122 patients on the ESHAP regimen were studied. RESULTS: Forty-five patients (37%) attained a complete remission (CR) and 33 (27%) attained a partial remission (PR), for a total response rate of 64%. The median duration of CR was 20 months, with 28% of remitters still in CR at 3 years. The overall median survival duration was 14 months; the survival rate at 3 years was 31%. Overall time to treatment failure (TTF) showed 10% of all patients to be alive and disease-free at 40 months. Response and survival rates were similar in patients with low-grade (n = 34), intermediate-grade (n = 67), transformed (n = 18), and high-grade (n = 3) lymphoma. The most significant factors for response and survival by multivariate analysis were the serum lactic dehydrogenase (LDH) level, tumor burden, and age (when analyzed as a continuous variable), while prior CR was highly significant by univariate analysis. A significant difference in survival was noted for patients with normal LDH levels and low- or intermediate-tumor burden or patients with low tumor burden and elevated LDH levels (55% 3-year survival rate) versus patients with elevated LDH levels and intermediate or high tumor burden (< 20%). Major toxicities included myelosuppression, with a median granulocyte count of 500/microL and platelet count of 70,000/microL. CONCLUSION: ESHAP was found to be an active, tolerable chemotherapy regimen for relapsing and refractory lymphoma. Applying a prognostic model based on tumor burden and serum LDH level shows significant differences in survival in this patient population. PMID- 8201380 TI - Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for recurrent follicular lymphoma. AB - PURPOSE: To assess myeloablative therapy with autologous bone marrow transplantation (ABMT) in younger patients with follicular lymphoma in the hope of prolonging remission duration and survival. PATIENTS AND METHODS: Since June 1985, 64 patients with follicular lymphoma have received cyclophosphamide (CY) 60 mg/kg x 2 and total-body irradiation (TBI) 2 Gy x 6 supported by ABMT as consolidation of second or subsequent remission. The marrow mononuclear cell (MNC) fraction was treated in vitro with three cycles of the monoclonal antibody (MAb) anti-CD20 and baby rabbit complement before cryopreservation. At the time of treatment, 34 patients were in complete remission (CR), and 30 had residual disease present. RESULTS: The median time to engraftment was 28 days (range, 15 to 46) for both a neutrophil count greater than 0.5 x 10(9)/L and a platelet count greater than 20 x 10(9)/L. Engraftment did not occur in one patient who died at 12 weeks, and three patients (excluded from the range) have had delayed recovery (> 6 months) of RBCs and platelets. Fifty two patients are alive; three died as a consequence of the transplant procedure, two died in remission from other causes, and seven died of recurrent lymphoma. There was a significant correlation between survival and the total number of episodes of treatment required during the course of the illness (< or = to three v > three, P = .01). With a median follow-up duration of 3 1/2 years, 35 patients continue in remission between 1 and 8 years, and 24 have developed recurrent lymphoma, five with evidence of transformation to high-grade histology. Freedom from recurrence did not correlate with the time from diagnosis, the number of previous treatments, the presence or absence of residual disease at the time of treatment, or during which specific remission the treatment was given (second v > second). However, comparison with an age-matched, remission-matched, historical control group shows a significant advantage in favor of treatment with CY plus TBI plus ABMT (P = .001); currently, there is no difference in survival. CONCLUSION: These results are encouraging, although preliminary; it remains to be established whether this treatment prolongs survival. PMID- 8201381 TI - Use of retinoic acids in the treatment of peripheral T-cell lymphoma: a pilot study. AB - PURPOSE: We have systemically analyzed, both in vitro and in vivo, the effect of 13-cis-retinoic acids (RA) on non-Hodgkin's lymphoma (NHL). METHODS: The in vitro growth-inhibitory effect of 13-cis-RA was examined in 11 (T cell, five; B cell, six) lymphoma cell lines by a tetrazolium colorimetric assay. A pilot clinical trial with oral 13-cis-RA 1 mg/kg/d was conducted in a selected group of 18 lymphoma patients, of whom 16 had failed to respond to at least one regimen of intensive chemotherapy. The in vitro and in vivo effects of 13-cis-RA were correlated with immunophenotypes, RA-induced changes of morphology, and patterns of DNA fragmentation of the lymphoma cells. RESULTS: Four of five T-lymphoma cell lines and none of six B-lymphoma cell lines were sensitive (concentration of 50% growth inhibition [IC50] < 1.5 microns) to 13-cis-RA (P = .015). In the clinical trial, five (two Ki-1, one angioinvasive type, one diffuse mixed cell, and one diffuse large cell) complete remissions and one (Ki1) partial remission were observed in 12 patients with peripheral T-cell lymphoma (PTCL), while none of six patients with B-cell lymphoma responded to 13-cis-RA. 13-cis-RA-induced cellular differentiation and apoptosis, as evidenced by the more mature morphology, characteristic nuclear condensation, and DNA ladder pattern signifying internucleosomal fragmentation, were demonstrated in the sensitive cell lines, as well as in the remitting lymphoma tissues. CONCLUSION: The 13-cis-RA appears to be active on lymphomas of T-lineage and their therapeutic indication may be extended to include some subtypes of PTCL. The mechanisms of action are related to differentiation and apoptosis of lymphoma cells. There appears to be no cross resistance between 13-cis-RA and conventional chemotherapy. PMID- 8201382 TI - Antibody targeting in metastatic colon cancer: a phase I study of monoclonal antibody F19 against a cell-surface protein of reactive tumor stromal fibroblasts. AB - PURPOSE: To define the toxicity, imaging, and biodistribution characteristics of iodine 131-labeled monoclonal antibody F19 (131I-mAbF19). MAbF19 recognizes the fibroblast activation protein (FAP), a cell-surface glycoprotein not present in most normal tissues, but abundantly expressed by reactive stromal fibroblasts of epithelial cancers, including more than 95% of primary and metastatic colorectal carcinomas. PATIENTS AND METHODS: 131I-mAbF19 was administered intravenously to 17 patients with hepatic metastases from colorectal carcinoma who were scheduled for resection of localized metastases or insertion of hepatic artery catheter for regional chemotherapy. Seven to 8 days before surgery, patients received 131I mAbF19 at three dose levels, with at least four patients entered at each level. RESULTS: No toxicity associated with intravenous 131I-mAbF19 administration was observed. Tumor images were obtained on planar and single-photon emission tomography (SPECT) scans in 15 of 17 patients with hepatic metastases, tumor infiltrated portal lymph nodes, and/or recurrent pelvic disease. The smallest lesion visualized was 1 cm in diameter. The optimal time for tumor imaging was 3 to 5 days after 131I-mAbF19 administration. The use of image registration techniques allowed precise anatomic localization of 131I-mAbF19 accumulation. Immunohistochemical analysis of biopsy tissues showed expression of FAP in the tumor stroma (but not in normal liver) in all patients studied and confirmed that the FAP-positive tumor stromal fibroblasts were interposed between the tumor capillaries and the malignant colon epithelial cells. At the time of surgery, tumor-to-liver ratios up to 21:1 and tumor-to-serum ratios up to 9:1 were obtained. The fraction of the injected 131I-mAbF19 dose per gram tumor (%ID/g tumor) localized to hepatic metastases at the time of surgery ranged from 0.001% to 0.016%. CONCLUSION: The FAP tumor fibroblast antigen is highly expressed in primary and metastatic colorectal carcinomas and shows limited expression in normal adult tissues. This highly selective expression pattern allows imaging of colorectal carcinoma lesions as small as 1 cm in diameter on 131I-mAbF19 scans. Because of the consistent presence of FAP in the stroma of epithelial cancers and the accessibility of FAP-positive tumor stromal fibroblasts to circulating monoclonal antibodies (mAbs), this study suggests possible diagnostic and therapeutic applications of humanized mAbF19 and mAbF19 constructs with novel immune and nonimmune effector functions. PMID- 8201383 TI - Hepatic arterial infusion of floxuridine, leucovorin, doxorubicin, and cisplatin for hepatocellular carcinoma: effects of hepatitis B and C viral infection on drug toxicity and patient survival. AB - PURPOSE: To conduct a pilot trial of hepatic arterial infusion (HAI) of floxuridine (FUDR), leucovorin, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (FLAP) in nonresectable hepatocellular cancer (HCC) confined to the liver and assess the effects of hepatitis B (HBV) and hepatitis C (HCV) viral markers on toxicity, response to treatment, and patient survival. PATIENTS AND METHODS: Of 31 HCC patients, 13 were HBV- and HCV-nonreactive, and 18 had evidence of either current or prior HBV and/or HCV infection. Treatment was delivered through percutaneous hepatic arterial catheters, and Infusaid pumps (Shiley Infusaid, Norwood, MA) were placed in responding patients. Cisplatin (100 mg/m2) and Adriamycin (30 to 35 mg/m2) were administered on day 1, followed by a continuous 24-hour HAI of an admixture of floxuridine (60 mg/m2) and leucovorin (15 mg/m2) daily for 4 days. Treatment was repeated every 5 weeks. RESULTS: Twelve (41%) of 29 assessable patients had a partial response (PR), with a median time to disease progression of 13 months. Six (50%) of 12 HBV-negative (HBV-)/HCV negative (HCV-) and six of 17 (35%) HBV-positive (HCV+) and/or HCV-positive (HCV+) patients achieved a PR. Eight patients have been maintained in remission for a median duration greater than 15.5 months. The median survival duration of all 31 patients was 15 months, 7.5 months among HBV+ and/or HCV+ patients, and significantly longer among hepatitis-non-reactive patients (P = .007). (A median has not yet been reached.) Granulocylopenia (< 0.1 x 10(3)/microL), thrombocytopenia (< 25 x 10(3)/microL), and hospitalizations for infectious complications were significantly more common among HBV-HCV-reactive than nonreactive patients: 56%, 50%, and 67% versus 15%, 15%, and 8%, respectively (P < .05 for all). CONCLUSION: HAI of FLAP has induced long-term PR and has palliated extensive nonresectable HCC. Positive hepatitis serology appeared to increase bone marrow susceptibility to myelotoxic drugs. Conceivably, one or both viruses may have a direct inhibitory effect on bone marrow progenitors and thereby contribute to the observed myelotoxicity. PMID- 8201384 TI - Medulloblastoma in very young children: outcome of definitive craniospinal irradiation following incomplete response to chemotherapy. AB - PURPOSE: To evaluate survival and neurodevelopmental outcomes following radiation therapy in infants and young children with residual or progressive medulloblastoma after primary chemotherapy. PATIENTS AND METHODS: Thirteen young patients (< or = 36 months old) with medulloblastoma were treated with preirradiation multiagent chemotherapy and maximal surgical resection. Patients were scheduled to receive radiation therapy at the time of documented disease progression or upon completion of chemotherapy with residual disease. All patients underwent neurodevelopmental evaluation at the time of diagnosis, before receiving radiation therapy, and at yearly intervals posttreatment. RESULTS: Two patients completed the scheduled chemotherapy with residual disease and received delayed radiation therapy. The remaining 11 patients had either local or leptomeningeal progression during chemotherapy (median time to progression, 5 months). Six patients had a complete response (CR) to radiation therapy, and three of these children are alive 48 to 104 months postdiagnosis. Of the five patients who had progressive disease (PD) during radiation therapy or residual imaging abnormalities after treatment, only one is alive (with stable enhancing leptomeningeal abnormalities) 48 months postirradiation. Two additional survivors were rendered disease-free by surgical resection before radiation therapy and are without evidence of disease at 91 and 107 months after diagnosis. Thus, six of 13 patients are alive at 48 to 107 months postdiagnosis. Neurodevelopmental scores tended to be below age norms at diagnosis; scores improved during chemotherapy, but then decreased during posttreatment follow-up evaluation. CONCLUSION: Radiation therapy appears to produce long-term disease-free survival in a proportion of very young patients who have progressive or residual medulloblastoma during or after primary chemotherapy. However, neurodevelopmental deficits are frequent among long-term survivors. PMID- 8201385 TI - Allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: impact of conditioning regimen without total-body irradiation--a report from the Societe Francaise de Greffe de Moelle. AB - PURPOSE: To analyze the French experience of chemotherapeutic preparation before human leukocyte antigen (HLA)-identical bone marrow transplantation (BMT) in children with acute myeloblastic leukemia (AML) in first complete remission (CR). PATIENTS AND METHODS: The data base used for this study was a French BMT registry for childhood AML. Twenty-three children were conditioned with busulfan and 120 mg/kg cyclophosphamide (Bu-Cy 120 group). Nineteen received busulfan and 200 mg/kg cyclophosphamide (Bu-Cy200 group). During the same time period, 32 patients were prepared with total-body irradiation (TBI group) most often in combination with 120 mg/kg of cyclophosphamide. RESULTS: The probability of relapse was 54%, 13%, and 10% for the Bu-Cy120, Bu-Cy200, and TBI groups, respectively (P < .05 in the univariate analysis, log-rank test, 2 df). In the multivariate analysis, a conditioning regimen with Bu-Cy120 was significantly associated with a higher risk of relapse (P = .02; relative risk, 3.62). The probability of transplant related mortality (TRM) was 0% for Bu-Cy120, 5% for Bu-Cy200, and 10% for TBI. Kaplan-Meier estimations of event-free survival (EFS) were 46% +/- 24%, 82% +/- 18%, and 80% +/- 14%, respectively, for the three groups, with median follow-up durations of 28 months (range, 3 to 78), 31 months (4 to 68), and 48 months (2 to 73). In the multivariate analysis, two factors adversely affected EFS: a conditioning regimen with Bu-Cy120 (P = .07) and a long interval from diagnosis to BMT (> or = 120 days, P = .08). CONCLUSION: Bu-Cy120 is a well-tolerated preparation, but results in a high risk of relapse for children with AML in first CR. This high risk of relapse is not observed when the dose of cyclophosphamide is increased to 200 mg/kg. PMID- 8201386 TI - Ifosfamide, carboplatin, and etoposide plus granulocyte-macrophage colony stimulating factor: a phase I study with apparent activity in non-small-cell lung cancer. AB - PURPOSE: A phase I trial was performed to evaluate the feasibility of escalating the dose of etoposide in dose-intensive ifosfamide, carboplatin, and etoposide (ICE) with granulocyte-macrophage colony-stimulating factor (GM-CSF). PATIENTS AND METHODS: Twenty-four patients were entered between November 1990 and November 1991. Patients received ifosfamide 5 g/m2 by continuous infusion over 48 hours, carboplatin 400 mg/m2 by intravenous bolus, and GM-CSF 5 micrograms/kg/d subcutaneously from day 4 until neutrophil recovery. The etoposide dose was escalated, with six patients receiving 300 mg/m2 total dose (level 1), six receiving 600 mg/m2 (level 2), three receiving 900 mg/m2 (level 3), and five receiving 1,200 mg/m2 (level 4). Level 4B consisted of three patients who received etoposide 1,200 mg/m2 and GM-CSF 10 micrograms/kg/d. Cycles were repeated every 21 days. The maximum-tolerated dose (MTD) was prospectively defined as the dose level at which the next higher level produced greater than 7 days of grade 4 myelosuppression in two or more of six patients. RESULTS: Twenty three patients were assessable. The median duration of neutropenia was < or = 7 days on cycle 1 at all dose levels. The initial criteria for determination of the MTD was never achieved. However, seven of eight patients treated at levels 4 and 4B required hospitalization for neutropenic fever on cycle 1 of therapy, with three of four septic events occurring at these levels. Cumulative thrombocytopenia occurred at all dose levels, with > or = 50% of patients requiring platelet transfusions on cycle 3. This became the dose-limiting toxicity above level 3. The overall response rate was 48%, with 11 of 23 objective responses, including two complete responses (CRs). Seven of 11 (64%) patients with non-small-cell lung cancer (NSCLC) responded, including one CR. Two of four (50%) heavily pretreated non-Hodgkin's lymphoma (NHL) patients responded, with one CR. CONCLUSION: The addition of GM-CSF to a dose-intensive ICE regimen permitted dose escalation of etoposide to 900 mg/m2, with cumulative thrombocytopenia as the dose-limiting toxicity. Carboplatin dosing by the area under the curve (AUC) may minimize thrombocytopenia. This appears to be an active regimen for patients with NSCLC and refractory NHL. PMID- 8201387 TI - Phase II study of continuous infusion fluorouracil with epirubicin and cisplatin in patients with metastatic and locally advanced breast cancer: an active new regimen. AB - PURPOSE: To investigate the efficacy and toxicity of continuous infusion fluorouracil (5-FU) with every-3-weeks epirubicin and cisplatin (ECF) in advanced breast cancer in a phase II study. PATIENTS AND METHODS: Forty-three patients with metastatic (n = 29) or locally advanced/inflammatory (n = 14) breast cancer were treated with 5-FU 200 mg/m2/d via a Hickman line using an ambulatory pump for 6 months with epirubicin 50 mg/m2 intravenously (IV) and cisplatin 60 mg/m2 IV every 3 weeks, for eight courses. RESULTS: The overall response rate (complete plus partial) was 84% (95% confidence interval [Cl], 76% to 96%), with a complete response rate of 24% (95% Cl, 9% to 40%) in patients with metastatic disease and 36% (95% Cl, 11% to 61%) in patients with locally advanced disease. The main World Health Organization [WHO] grade 3 or 4 toxicities included leukopenia, emesis, and alopecia. CONCLUSION: Infusional ECF is a highly active regimen in advanced breast cancer and warrants evaluation in high-risk early breast cancer. PMID- 8201388 TI - Thromboembolic complications after perioperative chemotherapy in women with early breast cancer: a European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group study. AB - PURPOSE AND METHODS: Data from a randomized phase III trial in early breast cancer, comparing surgery followed by one short intensive course of perioperative fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus surgery alone, were analyzed for the occurrence of thromboembolic complications within 6 weeks after surgery. RESULTS: Twenty-seven of 1,292 patients assigned to the perioperative chemotherapy treatment arm (2.1%) and 10 of 1,332 patients on observation (0.8%) developed thromboembolic events (P = .004). The frequency of thromboembolic complications was higher among postmenopausal women compared with premenopausal women (2.0% v 0.6%, P = .003). Patients who had mastectomy had a higher frequency of thromboembolic disease than those who had tumorectomy (2.3% v 0.7%, P < .001). Three deaths occurred after pulmonary embolism, all of them in the perioperative chemotherapy treatment arm. CONCLUSION: These results suggest a contributing role of perioperative chemotherapy to thromboembolic disease, especially in postmenopausal women and women undergoing mastectomy. Antithrombosis prophylaxis should be considered in the case of adjuvant perioperative chemotherapy. PMID- 8201389 TI - Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. AB - PURPOSE: To evaluate the natural history, validate previous observations, and identify prognostic factors in patients with unknown primary carcinoma (UPC). PATIENTS AND METHODS: Nine hundred twenty-seven consecutive patients referred to the M.D. Anderson Cancer Center with a preliminary diagnosis of UPC were prospectively identified. A standardized evaluation narrowed the study population to 657 patients with UPC. All data were recorded and computerized for storage, retrieval, and analysis. The primary end point for the study was survival, which was calculated from the first day of patient registration. Survival curves were estimated using the Kaplan-Meier method and compared using the Cox-Mantel log rank test. To identify important prognostic factors, univariate and multivariate analyses were conducted. RESULTS: The demographics of the UPC patient population mirrored those of the general population of patients referred to our cancer center except for an excess of men among the UPC patients. Most patients had histologic or cytologic evidence of adenocarcinoma and had more than one organ site metastatically involved. Univariate and multivariate analyses identified numerous important prognostic factors with a significant influence on survival, including sex, number of organ sites involved, specific organ sites involved, and pathologic subtypes. CONCLUSION: This study validated previously identified important prognostic factors for survival in UPC. Additional variables that had an impact on survival were identified and the complex interaction of the factors was explored. As patient numbers increase, this database will be able to provide further analyses of patient subsets and potentially relate specific clinical features to the evolving molecular and biochemical understanding of these malignancies. PMID- 8201390 TI - Results of a clinical trial in humans with refractory cancer of the intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl, in combination with various single antineoplastic agents. AB - PURPOSE: We assessed N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl (DPPE) potentiation of chemotherapy in vitro and performed a pharmacokinetic study and phase I/II trial of DPPE, combined with various single agents, in patients with advanced refractory cancer. PATIENTS AND METHODS: In vitro chemopotentiation by DPPE was assessed in drug-sensitive and -resistant (multidrug resistant-positive [MDR+]) human tumor cells using a colony survival assay. The effect of DPPE and verapamil on the intracellular concentration of daunorubicin in MDR+ cells was compared. For the clinical study, subjects with progressive malignancy received a weekly infusion of a maximally tolerated dose of DPPE (240 mg/m2) over 80 or 440 minutes, in conjunction with a single chemotherapy drug to which, in most cases, the patient's tumor was previously resistant. Concentrations of DPPE in blood and urine were determined by high-performance liquid chromatography (HPLC). RESULTS: In vitro, micromolar concentrations of DPPE potentiated (fivefold to 10-fold) chemotherapy cytotoxicity to both drug-sensitive and -resistant cells, but did not inhibit the p-glycoprotein pump; in vivo, serum levels of DPPE were 3 to 5 mumol/L at the end of 80 minutes and 1 to 2 mumol/L after 440 minutes of infusion. Of 48 patients monitored for a minimum of four DPPE/chemotherapy treatment cycles, 16 (33%) progressed, 12 (25%) stabilized, 12 (25%) improved, and eight (17%) responded (one complete and seven partial remissions). Four of 11 subjects who did not respond to the 80-minute infusion regimen improved with the 440-minute infusion; one had a partial remission of melanoma. In more than 600 patient-treatments, bone marrow toxicity was negligible (mean absolute neutrophil count [ANC] > 2.0 x 10(9)/L). Acute CNS symptoms associated with DPPE infusions were of relatively short duration (1 to 4 hours); delayed toxicity attributable to DPPE consisted of mild nausea and/or fatigue (1 to 2 days). CONCLUSION: Although preliminary, the results suggest that more structured trials should be performed to determine whether DPPE may increase the therapeutic index of certain chemotherapy drugs. PMID- 8201391 TI - Relationship between fluorouracil systemic exposure and tumor response and patient survival. AB - PURPOSE: The aim of this study was to analyze the link between fluorouracil (FU) systemic exposure and tumor response and overall survival. PATIENTS AND METHODS: One hundred eighty-six patients (162 men, 24 women) with head and neck cancer were studied. All received cisplatin plus FU for three cycles as first-line chemotherapy. The treatment consisted of cisplatin (100 mg/m2 intravenously [IV]) followed by a 5-day continuous venous infusion of FU (1 g/m2/d). The median follow-up duration for the 104 patients alive was 24 months. For each cycle, we calculated the area under the curve over the duration of pharmacokinetic follow up (AUC0-105 h) for plasma FU. For each patient, we analyzed the averaged AUC0 105 h and the averaged total dose for the three cycles. RESULTS: The response rate was 30% complete responses (CRs), 22% partial responses (PRs) more than 75%, 25% PRs less than 75%, and 23% no response (NR). Medians for averaged AUC and dose per cycle were 27,906 ng/mL h (first through third quartile, 25,398 to 31,060) and 7,000 mg (first through third quartile, 6,200 to 7,833), respectively. The tumor response was significantly linked to tumor stage (P < .001) and to averaged AUC (P = .05), but not to averaged dose. Analysis of parameters (continuous variable) expressing FU treatment intensity showed that dose did not influence survival contrary to the AUC (P = .001). The AUC remains significant (P = .025) in a multivariate analysis including tumor stage, demonstrating that the greater the FU systemic exposure, the longer the survival. CONCLUSION: These results strengthen the interest of individual FU dose adaptation based on pharmacokinetics. PMID- 8201392 TI - Adjuvant chemotherapy for breast cancer: discordance between physicians' perception of benefit and the results of clinical trials. AB - PURPOSE: Decisions about management of patients depend on the perception of physicians about the results of clinical trials. We therefore determined whether physicians would recommend adjuvant chemotherapy for specified patients with breast cancer, and whether the perceived levels of benefit that led to these decisions were supported by the results of clinical trials. METHODS: We mailed a questionnaire that presented two clinical scenarios to 515 American and European oncologists. Scenario A depicted a premenopausal woman with node-negative, estrogen receptor-negative (ER-) breast cancer, and scenario B depicted a post menopausal woman with node-positive, ER- disease. Respondents were asked about the evidence that they required from clinical trials to recommend adjuvant chemotherapy for these patients. RESULTS: Replies were received from 307 oncologists. American respondents were more likely to recommend adjuvant chemotherapy than Europeans (A, 93% v 68%; B, 85% v 67%; P < .001 for both comparisons). Opinion was evenly divided as to whether improvement in the relapse free survival (RFS) rate was sufficient to recommend treatment, or whether improvement in overall survival was necessary. Mean values of 12.9% to 14.6% improvement in RFS at 3 years, or 10.7% to 12.4% improvement in overall survival at 5 years, were required to offer treatment. An overview analysis of clinical trials suggests that adjuvant chemotherapy achieves absolute improvements of 6% to 9% in RFS rates at 3 years and 3% to 4% in overall survival rates at 5 years for patients in these scenarios. CONCLUSIONS: Most oncologists recommended treatment in these scenarios, but require a level of treatment effect that has not been demonstrated in clinical trials. Our results suggest that oncologists' perceptions of the results of clinical trials overestimate the therapeutic gain from use of adjuvant chemotherapy for breast cancer. PMID- 8201393 TI - The take-home message: patients prefer consultation audiotapes to summary letters. AB - PURPOSE: Despite reports of poor patient understanding and recall after cancer consultations, few doctors provide communication aids. We conducted a randomized trial comparing an audiotape of the consultation versus individualized summary letters to patients after their first consultation with a medical oncologist. METHODS: One hundred eighty-two cancer patients were randomized to receive either (1) the audiotape followed 7 to 10 days later by the letter or (2) the letter followed by the audiotape. Outcome measures included patient recall, anxiety and depression, satisfaction with and use of the communication aids, and patient preferences for six communication options. Demographic and disease variables and information and involvement preferences were documented. RESULTS: Eighty percent of patients wanted all information and 72% wanted to participate in treatment decisions. Patients listened to the tape on average 2.3 times and read the letter 2.8 times over 4 weeks, and 90% showed the tape or letter to a friend, relative, or doctor. Satisfaction with the tape and letter were uniformly high and they did not differentially affect recall, anxiety, or depression. When asked to rank six communication options, 46% of patients gave the highest rank to the tape and 21% to the letter. CONCLUSION: Patients use audiotapes of their cancer consultation and individualized letters to review the information given and communicate information to relatives and friends. They prefer audiotapes to letters. Clinicians should consider installing audiotape-recording facilities that could be used to tape new-patient consultations. PMID- 8201394 TI - Management of adult acute lymphocytic leukemia: present issues and key challenges. AB - PURPOSE: To discuss the controversies in current adult acute lymphocytic leukemia (ALL) management in relation to its different phases of therapy. DESIGN: A review of treatments in adult ALL from the English literature. RESULTS: Features signaling high risk for systemic relapse (older age, high WBC count at diagnosis, non-T-cell immunophenotype, Philadelphia chromosome (Ph)-positive karyotype, and longer time to achieve remission) are found in 60% to 70% of patients with adult ALL. These patients have a potential cure rate of 20% to 25%, compared with 60% to 70% for low-risk patients. Induction regimens with vincristine, anthracyclines, and corticosteroids appear to be optimal. Intensification consolidation therapy increased cure rates modestly in adult ALL; higher-dose schedules of mercaptopurine (6-MP), methotrexate, and asparaginase may be beneficial. Maintenance therapy with 6-MP and methotrexate is suggested based on the worse outcome of patients in whom such maintenance was omitted. Allogeneic bone marrow transplantation (BMT) is indicated for patients in first remission with high-risk for relapse; autologous BMT for patients in first remission remains investigational. Patients with mature B-cell ALL require short-term, dose intensive therapy that alternates hyperfractionated doses of cyclophosphamide with high-dose cytarabine (ara-C) and methotrexate. Patients with T-cell ALL may benefit from ara-C/cyclophosphamide combinations during maintenance therapy. CNS prophylaxis with intrathecal chemotherapy should be administered in patients at risk for CNS relapse. CONCLUSION: Potential strategies to improve the prognosis of high-risk patients with ALL include increasing the dose-intensity of remission induction and consolidation-intensification therapies with growth factor support; discovering and using new anti-ALL drugs; improving autologous BMT results; translating biologic studies of leukemia cell characteristics, karyotype-related molecular aberrations, abnormal oncogenic expression, and minimal residual disease into clinically relevant therapies; and using investigational treatment strategies in high-risk patients. PMID- 8201395 TI - Treatment of hepatocellular carcinoma: too many options? AB - PURPOSE: This study attempts to review the therapeutic interventions being used to treat patients with hepatocellular carcinoma (HCC). DESIGN: An English language literature search, including abstracts and original articles, and a review of the bibliographies of such articles, was conducted. RESULTS: Surgery is possible in few patients and curative in only a small percentage. Conventional chemotherapy is ineffective in HCC. Modifications of chemotherapy, including intraarterial infusion, chemoembolization, lipiodol, styrene-maleic acid neocarzinostatin (SMANCS), and isolated hepatic perfusion, have led to improved tumor responses, but have not materially affected patient outcome. Radioimmunotherapy and conformal radiotherapy have had no more than a marginal impact on patient outcome. Surgical innovations such as cryosurgery and percutaneous alcohol injection have not yet been shown to offer any advantage, and liver transplantation, while curative in some patients, requires an enormous expenditure of resources to achieve cure in few patients. CONCLUSION: Prevention is the ideal approach to HCC. Surgical cure is rarely possible, and while numerous therapies may palliate symptoms, patient selection and the lack of randomized studies make their impact on median survival difficult to assess. Patients being treated for HCC should be enrolled on treatment protocols testing multimodality or new strategies. PMID- 8201396 TI - Gallium scans for residual Hodgkin's disease. PMID- 8201397 TI - Combination chemotherapy for metastatic melanoma: the importance of tamoxifen. PMID- 8201398 TI - Spinothalamic and spinohypothalamic tract neurons in the cervical enlargement of rats. III. Locations of antidromically identified axons in the cervical cord white matter. AB - 1. Fifty-five neurons in the cervical enlargement (C6-C8) of urethan-anesthetized rats were antidromically activated from the contralateral posterior diencephalon. In all cases, antidromic thresholds were < or = 30 microA. The locations of the axons of these neurons within the white matter of segments C2-C6 were determined by tracking systematically using a second antidromic stimulating electrode. 2. The recording locations of 51 neurons were marked and recovered. Twenty neurons were recorded in the superficial dorsal horn (SDH) and 31 were in the deep dorsal horn (DDH). Eighty-three lowest threshold points for antidromic activation within the white matter of segments C2-C6 were determined for these 51 neurons. The mean antidromic threshold at these points was 9.5 +/- 0.5 (SE) microA. For 26 neurons, the lowest threshold point for antidromic activation was determined at one segmental level. We also attempted to determine whether individual axons maintained their position as they ascended through the cervical cord white matter. In 25 cases, lowest threshold points were determined at two or more segmental levels. 3. In segments C5-C6, 88% (7/8) of the lowest threshold points of the examined axons were located in the contralateral ventral funiculus, indicating that the majority of examined axons crossed the midline within one or two segments. 4. In segments C3-C4, 32% (14/44) of all examined axons were found in the dorsal lateral funiculus (DLF) and 66% (29/44) were within the ventral quadrant [ventral lateral funiculus (VLF) and ventral funiculus (VF)]. Sixty-nine percent (11/16) of the axons of neurons recorded in the SDH were located in the contralateral DLF and 31% (5/16) were located in the ventral quadrant (VQ). In contrast, only 11% (3/28) of the axons of neurons recorded in the DDH were located in the contralateral DLF and 86% (24/28) were located in the VQ. Therefore, in segments C3-C4, the locations of axons differed significantly. Those from neurons recorded in the SDH were located primarily in the DLF and those from neurons recorded in the DDH were located principally in the VQ. 5. In segment C2, 74% (23/31) of all examined axons were found in the DLF, 23% (7/31) were in the VQ, and 3% (1/31) were in the dorsal horn. Thus, the percentage of all examined axons in the DLF in C2 was approximately 2.5 times greater than it was in C3-C4.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201399 TI - Enhancement of neural synchronization in the anteroventral cochlear nucleus. I. Responses to tones at the characteristic frequency. AB - 1. Encoding temporal features of the acoustic waveform is an important attribute of the auditory system. Auditory nerve (AN) fibers synchronize or phase-lock to low-frequency tones and transmit this temporal information to cells in the anteroventral cochlear nucleus (AVCN). Phase-locking in the AVCN is usually reported to be similar to or weaker than in the AN. We studied phase-locking in axons of the trapezoid body (TB), which is the output tract of the AVCN, and found, to our surprise, that most TB axons exhibited enhanced synchronization compared with AN fibers. 2. Responses from axons in the TB of the cat were obtained with horseradish peroxidase (HRP)- or Neurobiotin-filled micropipettes or metal microelectrodes. A series of short tone bursts at increasing sound pressure level (SPL) was presented at the characteristic frequency (CF) of the fiber and phase-locking was quantified with the vector strength R at each SPL. For each fiber the maximum R value (Rmax) was then determined. 3. Low-frequency fibers in the TB showed very precise phase-locking: Rmax values could approach 0.99. For the majority of fibers (33/44, 75%) with CF < 700 Hz, Rmax was > or = 0.9 and therefore higher than is ever observed in the AN. We define such fibers as "high-sync." Most of these fibers also entrained to the stimulus, i.e., they fired a precisely timed action potential to almost every stimulus cycle. Some fibers showed perfect entrainment, with maximum discharge rates equaling the stimulus frequency. 4. To exclude the possibility that stimulus paradigms or acoustic and recording equipment were the source of this enhancement, we obtained additional data on low-frequency AN fibers using the same experimental protocol as in our TB experiments. These AN data agree well with published reports. 5. The morphological class of some of the cells studied was identified on the basis of anatomic features revealed by intra-axonal injection of HRP or Neurobiotin. Labeled low-CF axons (N = 7), which were all high-sync, originated from AVCN bushy cells: five were globular and two were spherical bushy cell axons. 6. Spontaneous rate of high-sync fibers covered a range from 0 to 176 spikes/s but were biased toward low values (mean 16 spikes/s). Responses to broadband clicks and sinusoidally amplitude-modulated signals provided additional evidence of improved timing properties.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201400 TI - Enhancement of neural synchronization in the anteroventral cochlear nucleus. II. Responses in the tuning curve tail. AB - 1. Discharges of neurons in the peripheral auditory system contain information about the temporal features of acoustic stimuli. Phase-locking of neurons in the anteroventral cochlear nucleus (AVCN) is usually reported to be less robust than in auditory nerve (AN) fibers, which provide their major input. In a companion paper we reported that some cells in AVCN of the cat show enhanced phase-locking compared with the AN when stimulated at the frequency to which they are most sensitive [characteristic frequency (CF)]. We called neurons "high-sync" when they showed vector strengths (R, a measure of phase-locking) > or = 0.9. Here we report phase-locking properties to stimuli at frequencies below CF. 2. Horseradish peroxidase-filled glass micropipettes or metal microelectrodes were inserted into the trapezoid body (TB), which is the large output tract of the AVCN. Acoustically driven fibers were classified on the basis of the shape of the poststimulus time (PST) histograms to short tone bursts at CF. We then presented low-frequency tones of increasing SPL and determined the maximum R value at 500 Hz (R500) for each fiber. Using the same experimental protocol we studied phase locking in the ANs of two animals because maximal R values at the tuning curve tail have not been reported for AN fibers. 3. Although phase-locking in AN fibers is usually assumed to be independent of CF, we found that fibers with CF > 2 kHz tended to have higher R500 values than fibers with CF < or = 2 kHz. Moreover, R500 was > or = 0.9 in 20% (42 of 196) of the fibers studied and could be as high as 0.95. This population of fibers was defined as having "high-sync tails" and consisted almost entirely of fibers with low or medium spontaneous rate. 4. High CF TB fibers stimulated at 500 Hz showed very high phase-locking. High-sync tails (R500 > or = 0.9) were found in 41 of 70 TB fibers. For a subset of these fibers (1/3 in total: 23 of 70) phase-locking was higher than is ever observed in the AN (R500 > or = 0.95); these fibers were defined as showing synchronization "enhancement." Virtually all fibers showing synchronization enhancement had primary-like-with-notch (PLN) PST histograms. Chopper and primary-like fibers showed high-sync tails for CFs > 3 kHz. 5. Synchronization filter functions were obtained for high-CF AN fibers by determining maximum synchronization for a range of stimuli below CF.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201401 TI - Functional properties of rat and human neocortical voltage-sensitive sodium currents. AB - 1. The functional properties of sodium currents in acutely dissociated adult human, neonatal rat [postnatal day (P) 3 and P10], and mature rat (P21-23) neocortical pyramidal neurons were studied using whole-cell patch-clamp techniques. 2. The voltage dependence of activation and steady-state inactivation of neonatal rat sodium currents was shifted in the positive direction when compared with mature rat sodium currents. In contrast, no difference was detected between the voltage dependence of activation and steady-state inactivation of mature rat and adult human sodium currents. 3. The fast inactivation of rat (neonatal and mature) and human neocortical sodium currents were best fit with three components; a fast decay component, a slow decay component, and a persistent component. The magnitude of the persistent current in neocortical neurons averaged 1-3% of the peak current. Inactivation was faster for sodium currents in neonatal rat neocortical neurons than in mature neurons. No difference was detected in the kinetics of inactivation between mature rat and adult human sodium currents. 4. Saxitoxin (STX) inhibited neuronal sodium currents at nanomolar concentrations in neonatal and mature rat and adult human neocortical neurons. STX-insensitive channels were not detected. 5. STX affinity was also assayed using 3H-STX. A single high-affinity binding site was found in neonatal rat, mature rat, and adult human neocortical tissue. A developmental increase in STX binding site density in the rat neocortex was tightly correlated with the increase in the sodium current density (normalized to cell capacitance). Human neocortical tissue and mature rat neocortical tissue did not differ in STX binding site density or sodium current density. 6. From these electrophysiological and autoradiographic studies we conclude that 1) the increase in the normalized sodium current density and STX binding density with age postnatally reflects an increase in binding sites of sodium channels functionally expressed on neuronal membranes, 2) the functional differences in channel behavior with maturation can explain the higher threshold for excitation in neonatal neocortical neurons and the increase in accommodation or adaptation in firing in the mature neuron, and 3) mature rat neocortical neurons represent a valid model for the study of adult human pyramidal neocortical neurons in terms of Na+ channel expression and function. PMID- 8201402 TI - A model for dendritic Ca2+ accumulation in hippocampal pyramidal neurons based on fluorescence imaging measurements. AB - 1. High-speed fluorescence imaging was used to measure intracellular Ca2+ concentration ([Ca2+]i) changes in hippocampal neurons injected with the Ca(2+) sensitive indicator fura-2 during intrasomatic and synaptic stimulation. The results of these experiments were used to construct a biophysical model of [Ca2+]i dynamics in hippocampal neurons. 2. A compartmental model of a pyramidal neuron was constructed incorporating published passive membrane properties of these cells, three types of voltage-gated Ca2+ channels characterized from adult hippocampal neurons, voltage-gated Na+ and K+ currents, and mechanisms for Ca2+ buffering and extrusion. 3. In hippocampal pyramidal neurons imaging of Na+ entry during electrical activity suggests that Na+ channels, at least in sufficient density to sustain action potentials, are localized in the soma and the proximal part of the apical dendritic tree. The model, which incorporates this distribution, demonstrates that action potentials attenuate steeply in passive distal dendritic compartments or distal dendritic compartments containing Ca2+ and K+ channels. This attenuation was affected by intracellular resistivity but not membrane resistivity. 4. Consistent with fluorescence imaging experiments, a non-uniform distribution of Ca2+ accumulation was generated by Ca2+ entry through voltage-gated Ca2+ channels opened by decrementally propagating Na+ action potentials. Consequently, the largest increases in [C2+]i were produced in the proximal dendrites. Distal voltage-gated Ca2+ currents were activated by broad, almost isopotential action potentials produced by reducing the overall density of K+ channels. 5. Simulations of subthreshold synaptic stimulation produced dendritic Ca2+ entry by the activation of voltage-gated Ca2+ channels. In the model these Ca2+ signals were localized near the site of synaptic input because of the attenuation of synaptic potentials with distance from the site of origin and the steep voltage-dependence of Ca2+ channel activation. 6. These simulations support the hypotheses generated from experimental evidence regarding the differential distribution of voltage-gated Ca2+ and Na+ channels in hippocampal neurons and the resulting voltage-gated Ca2+ accumulation from action and synaptic potentials. PMID- 8201403 TI - Sound localization after unilateral lesions of inferior colliculus in the ferret (Mustela putorius). AB - 1. The ability of ferrets to localize sounds in space was determined before and after large unilateral lesions of the inferior colliculus. Three animals sustained restricted lesions that destroyed the inferior colliculus caudally but spared some tissue rostrally. These restricted lesions did not extend substantially beyond the cytoarchitectonic boundaries of the inferior colliculus. Four animals received more extensive lesions that destroyed all of the inferior colliculus, including the rostral pole. These lesions also involved to various degrees other midbrain structures, including the dorsal nucleus of the lateral lemniscus and the lateral tegmentum. Psychophysical curves and minimum audible angles were obtained for midline and left and right lateral fields. Comparisons were made of deficits ipsilateral and contralateral to the lesion. 2. The animals were tested in a semicircular apparatus with loudspeakers located at various positions around the periphery. Separate sound localization tests were conducted for midline, left, and right field positions. In each test the animals were trained first to discriminate between speakers separated by 60 degrees. They were then tested with progressively smaller angles of speaker separation to obtain their psychophysical threshold (minimum audible angle). All critical tests of sound localization were based on the ability of animals to identify the location of a 45-ms noise burst presented at the beginning of each trial. Correct responses were rewarded by delivery of a small quantity of water from spouts located around the perimeter of the apparatus. 3. Unilateral lesions restricted to the inferior colliculus had relatively little effect on sound localization. All three animals with restricted lesions were still capable of localizing a single noise burst and minimum audible angles were similar before and after surgery for midline, left, and right field tests. There was no difference in postoperative performance ipsilateral and contralateral to the lesion site. 4. More extensive unilateral lesions that included the dorsal nucleus of the lateral lemniscus and the lateral tegmentum as well as the inferior colliculus resulted in severe deficits in sound localization. Each of the four animals with large unilateral lesions had a substantial impairment in sound localization in the field contralateral to the lesion site. Postoperative performance in the contralateral field was too low to obtain a minimum audible angle for these animals. Midline sound localization was also affected in some cases but ipsilateral sound localization was only slightly affected. PMID- 8201404 TI - Presynaptic inhibition is mediated by histamine and GABA in the crustacean escape reaction. AB - 1. Presynaptic inhibition of sensory transmission during the escape reaction in Crustacea has been studied using an in vitro preparation of the crayfish thoracic ganglia. Electrical stimulation of the medial giant fiber mediating the escape reaction induced depolarization in sensory afferent terminals of the coxo-basal chordotonal organ (CBCO). This depolarization was associated with an increase of the membrane conductance and was partially blocked by a gamma-aminobutyric acid (GABA) antagonist, picrotoxin, and by a histamine antagonist, cimetidine. 2. Pressure ejection of histamine on CBCO sensory terminals (CBT) recorded intracellularly, induced a depolarization of the membrane potential accompanied by a large increase of the conductance. Histamine-induced depolarization persisted after blockade of synaptic transmission mediated by Na+ spikes by tetrodotoxin. The amplitude of histamine-induced depolarization increased when negative current was injected into the sensory terminal through the recording electrode. Moreover, injection of chloride into the CBT, which shifts the reversal potential of chloride to a more positive value, resulted in an increase of the amplitude of the histamine-induced depolarization. 3. The existence of separate receptors for GABA and histamine on the CB sensory terminals was demonstrated using two complementary sets of experiments. The first one consisted of using specific blockers of GABA and histamine. Picrotoxin blocked selectively the GABA-induced depolarization of the CB sensory terminals, while it was ineffective in blocking the histamine-induced depolarization. Conversely, cimetidine blocked the histamine-induced depolarization totally, but did not affect the GABA response. The second set of experiments tested for of cross desensitization between GABA and histamine responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201405 TI - Mechanical actions of heterogenic reflexes linking long toe flexors with ankle and knee extensors of the cat hindlimb. AB - 1. To study the means whereby ankle biomechanics are represented in the interneuronal circuitry of the spinal cord we examined stretch-evoked reflex interactions between the physiological extensors flexor hallucis longus (FHL) and flexor digitorum longus (FDL) as well as their interactions with gastrocnemius (G), soleus (S), and the quadriceps group (Q) in 34 unanesthetized decerebrate cats. To evoke stretch, DC motors provided ramp-hold-release length changes to tendons detached from their bony insertions. Semiconductor myographs measured resultant muscle force response. Reflexes were examined under both quiescent (no active force generation) and activated conditions; muscle activation was achieved through either crossed-extension or flexion reflexes. 2. FHL and FDL share mutual excitatory stretch-evoked interactions under most conditions examined. These interactions depended on muscle length, were asymmetric (with FHL contributing a larger magnitude of reflex excitation onto FDL), and occurred at a latency of 16 ms. Mutual Ia synergism previously described for these two muscles provides a basis for all of the above findings. Our data demonstrate that for this muscle pair, reflex connectivities revealed at the intracellular level can be extrapolated to cover the entire motoneuron pool; further, our data directly demonstrate the net mechanical result of ensemble synaptic events. 3. FHL was found to share strong, mutually inhibitory stretch-evoked interactions with G, S, and Q. Stepwise regression statistical analyses determined that these interactions depended on recipient muscle force and donor muscle force. These reflex interactions all occurred at a latency of 28 +/- 4 (SE) ms. Further, the heterogenic inhibition between FHL/G and FHL/S was attenuated by strychnine infusion (intravenous) but unaffected by either mecamylamine, picrotoxin, or baclofen infusion (intravenous, intrathecal). Disynaptic Ib inhibition previously described among hindlimb extensors provides a basis for the above findings; our data demonstrate that under certain conditions the ensemble activity of this system can cause a dramatic decline in whole muscle force output. 4. By contrast, FDL was found to share mutually inhibitory, stretch-evoked reflex interactions with G, S, and Q that were much weaker than those observed between FHL and these same muscles. The small magnitude of inhibition observed in these interactions made it difficult to assess reflex latency or to determine the factor(s) that best predicted the heterogenic inhibition. 5. This study provides further evidence of intrinsic differences in interneuronal organization between muscles whose activity occurs in a periodic manner during locomotion ("stereotypical") and a muscle whose locomotor activity is characterized by both periodic and nonperiodic components ("facultative").(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201406 TI - Characteristics of antidromically identified oculomotor internuclear neurons during vergence and versional eye movements. AB - 1. Previous studies have shown that midbrain near response cells that increase their activity during convergent eye movements project to medial rectus motoneurons, which also increase their activity during convergence. Most neurons in the abducens nucleus decrease their firing rate during convergence, and the source of this vergence signal is unknown. Oculomotor internuclear neurons (OINs) in monkeys project primarily from the medial rectus subdivisions of the oculomotor nucleus to the contralateral abducens nucleus, although there is a smaller ipsilateral projection as well. Because of these anatomic connections, it has been suggested that the OIN input may be responsible for the vergence signal seen on abducens neurons. The behavior of the OINs during eye movements and their synaptic drive are not known. Thus the goal of this study is to determine the behavior of these neurons during conjugate and disjunctive eye movements and to determine if these neurons have an excitatory or inhibitory drive on the abducens neurons. 2. Single-unit recording studies in alert rhesus monkeys were used to characterize the behavior of OINs. Eighteen OINs were identified by antidromic activation and collision testing. The recorded OINs displayed a burst-tonic pattern of activity during adducting saccades, and the majority of these cells displayed an increase in tonic activity with convergent eye movements. 3. Identified OINs were compared with a large sample of non-activated and untested horizontal burst-tonic cells in the medial rectus subdivisions of the oculomotor nucleus. The results indicate that the OINs behave similarly to medial rectus motoneurons during vergence and versional eye movements. None of the OINs displayed vertical eye position sensitivity. 4. Microstimulation of the oculomotor nucleus where both the OINs and medial rectus motoneurons were located resulted in a large adducting twitch of the ipsilateral eye and a smaller abducting twitch of the contralateral eye. The latter effect was presumed to be the result of OIN innervation of the contralateral abducens nucleus. This result suggests that the crossed OIN pathway is predominately, if not entirely, excitatory. 5. Injection of 10% lidocaine HCl into the medial rectus subdivision of the oculomotor nucleus caused a reversible inactivation of the medial rectus motoneurons and OINs. As expected, the inactivation of medial rectus motoneurons resulted in an exophoria and weakness of adduction for the eye ipsilateral to the lidocaine injection. In addition, the lidocaine injection resulted in hypometric and slowed abducting saccades in the eye contralateral to the injection site. This result also suggest that the crossed OIN pathway is excitatory.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201407 TI - Mechanism of early anoxia-induced suppression of the GABAA-mediated inhibitory postsynaptic current. AB - 1. We investigated the mechanism of hypoxia-induced depression of gamma aminobutyric acid-A (GABAA)-mediated inhibitory postsynaptic currents (IPSCs) in CA1 neurons of hippocampal slices from 21- to 28-day-old rats. Cells were examined by whole-cell patch-clamp recording and hypoxia was induced by switching perfusion of the slice from oxygenated artificial cerebral spinal fluid (ACSF) to ACSF saturated with 95% N2-5% CO2. 2. Synaptic responses evoked by stimulation of the Schaffer collateral-commissural projection at a fixed holding potential (VH = -60 mV) during anoxia revealed that the IPSC appeared more sensitive than the excitatory postsynaptic current to anoxia-induced depression. All subsequent studies examined the GABAA-mediated IPSC synaptic responses in isolation by direct stimulation of GABA interneurons in the stratum radiatum in the presence of extracellular 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP) (20 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (50 microM) to block glutamatergic currents and intracellular QX-314 (lidocaine N-ethyl bromide, 1 mM) to block GABAB-mediated currents. When studied in this manner (VH = -60 mV) the GABAA-mediated IPSC appeared to change from an outward to inward current after exposure to anoxia. 3. The current-voltage relationship of GABAA-mediated IPSCs revealed that these changes resulted from a positive shift in the IPSC reversal potential without a significant change in the conductance. Thus under patch clamp apparent IPSC inhibition may result from a decrease in the extracellular concentration of chloride ions. Similar findings were observed with micropipettes that contained high intracellular chloride concentrations. 4. Miniature spontaneous IPSCs were examined in the presence of tetrodotoxin (1 microM) with micropipettes containing high intracellular chloride concentrations. The miniature IPSCs (mIPSCs) appeared as spontaneous transient inward currents. Consistent with an anoxia-induced decrease in extracellular chloride, the mean amplitude of the mIPSCs increased after the onset of anoxia. A significant decrease in rise and decay time was also noted during anoxia. The frequency of the mIPSCs also increased by approximately 300%. 5. The resting input resistance of the cells was examined by measuring the current resulting from a 20-mV hyperpolarizing pulse. A significant reduction in resistance was observed 2 min after the onset of anoxia. This still occurred, although to a lesser degree, in the presence of glutamatergic blockers (20 microM CPP plus 50 microM CNQX). In the presence of both GABAergic (picrotoxin, 100 microM) and glutamatergic blockers no significant reduction in resting input resistance was apparent after 2 min of anoxia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201408 TI - Noradrenaline mediates paradoxical effects on rat neocortical neurons after GABA withdrawal. AB - 1. The aim of the present study was to determine the role of noradrenergic neurotransmission in neuronal activities intracellularly recorded in neocortical slices obtained from rats presenting the gamma-aminobutyric acid (GABA) withdrawal syndrome (GWS), a focal epilepsy consecutive to the interruption of a chronic intracortical GABA infusion into the somatomotor cortex. Neurons recorded in the epileptic focus area (n = 52) were bursting or nonbursting cells. Intrinsic bursting (IB, n = 20) cells presented bursts of action potentials (APs) to an intracellular depolarizing current injection and paroxysmal depolarization shifts (PDSs) to white matter stimulation. Synaptic bursting (SB, n = 22) cells presented only PDSs. Nonbursting (NB, n = 10) cells presented no burst after either synaptic stimulation or depolarizing current injection. Results were compared with those obtained from NB neurons (n = 4) recorded in slices from saline-infused rats. 2. In all of the recorded neurons, bath application of norepinephrine (NE, 10 and 100 microM) provoked a depolarization (1-5 mV) associated with a decrease in input K+ conductance having a mean reversal potential at -90 to -102 mV, not significantly different for bursting and nonbursting cells. This reversal potential differed from that of Cl(-)-mediated inhibitory postsynaptic potentials (-70 mV) elicited in NB cells by electrical stimulation of the white matter. 3. In IB cells, the NE-induced depolarization replaced the intrinsic bursts by a sustained repetitive discharge of single APs and caused intrinsic bursts to appear during previously subthreshold depolarizing current pulses. These NE-increased activities were abolished by dihydropyridine nitrendipine (1 microM) and by Cd2+ (0.5 mM) or Co2+ (2 mM), thus confirming that Ca2+ currents contribute to burst generation in IB cells. 4. In both NB and SB cells recorded in slices from GWS rats, NE provoked the appearance of intrinsic bursts of APs during steps of depolarizing current injections. In addition, in NB cells, NE caused synaptic bursts to appear after white matter stimulation. These NE-induced bursts were dihydropyridine (nitrendipine, 1 microM)- and Cd2+ (0.5 mM)- or Co2+ (2 mM)-sensitive and were related to an increased AP afterdepolarization. The fast AP-afterhyperpolarization was not affected by NE. In NB cells recorded in slices from saline-infused rats (n = 4) NE did not provoke the appearance of bursts even when stimulation intensity was increased up to three times.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201409 TI - Differential effects of muscimol microinjection into dorsal and ventral aspects of the premotor cortex of monkeys. AB - 1. A gamma aminobutyric acid (GABAA) receptor agonist, muscimol (Sigma, 5 micrograms/microliters solution), and a GABAB receptor agonist and antagonist, baclofen and phaclofen, respectively, were injected (1.0 microliter) into the dorsal and ventral aspects of the premotor cortex (PM) of two Japanese monkeys (Macaca fuscata), while they were performing a motor task that required wrist flexion or extension to a target. The correct movement was instructed by either 1) a conditional color cue [green or red light emitting diodes (LED)] equidistant from the targets or 2) a directional cue toward extension or flexion (right or left LED). When the green or right LED was illuminated, extension was to be performed. When the red or left LED was illuminated, flexion was required. The movement was triggered by a visual stimulus either simultaneously with the instruction stimulus or after a variable delay. 2. Before drug injection, single unit recordings were made to select injection sites 1) in the dorsal aspect of the PM (PMd) around the superior precentral sulcus where typical set-related activity was frequently recorded and 2) in the ventral aspect of the PM (PMv) immediately caudal to the genu of the arcuate sulcus where movement-related neurons were densely located. 3. Behavioral deficits were observed primarily at the time muscimol, but not baclofen or phaclofen, was injected. Furthermore, muscimol effects were short-lasting: deficits were most frequently observed during the 10-min injection period but seldom after completion of injection. 4. When muscimol was injected into the PMd, there was an increase in the number of direction errors primarily when the conditional cues were presented. The initiated movements were similar in amplitude and velocity to the preinjection behavior. In contrast, when muscimol was injected into the PMv, many of the initiated movements showed smaller amplitudes and slower velocities, but few direction errors were made. 5. These results suggest that the PMd and PMv play differential roles in motor control: the PMd is more important than PMv in conditional motor behavior and plays a role in the preparation for forthcoming movements. In contrast, the PMv is more specialized for a role in the execution of visually guided movements. PMID- 8201410 TI - Effects of anoxia on rat midbrain dopamine neurons. AB - 1. Dopamine-containing neurons of the rat midbrain were recorded intracellularly in vitro. Anoxia (2-5 min) caused reversible membrane hyperpolarization (4-25 mV), which blocked spontaneous firing of action potentials. Under voltage clamp, anoxia produced an outward current (100-1,000 pA) associated with an increase in the apparent input conductance. 2. The mean reversal potential of the anoxia induced response at 2.5 and 12.5 mM [K+] was -86 and -66 mV, respectively. 3. The effect of anoxia was not blocked by tetrodotoxin (TTX), saclofen, (-)sulpiride, or strychnine. Superfusate containing low calcium (0.5 mM CaCl2 and 10 mM MgCl2 or 0.5-1 mM CaCl2 and 1 mM CoCl2) or low sodium (25-40% of control) reduced the anoxia-induced outward current. 4. Extracellular barium (0.1-1 mM) blocked the anoxia-induced hyperpolarization/outward current. Other K+ channel blockers (tetraethylammonium, apamin, quinine, and glibenclamide) failed to reduce anoxia induced current. 5. When the dopamine-containing neurons were loaded with cesium (1-2 mM), anoxia caused a reversible membrane depolarization and a block of the firing activity. This depolarization was voltage dependent; it was decreased or blocked by the hyperpolarization of the membrane. 6. Perfusion of the cells with 0.5-1 microM TTX did not affect the membrane depolarization/inward current caused by anoxia. These were also present when the cells were treated with the excitatory amino acid receptor antagonists D,L-2-amino-5-phosphonovalerate (APV) (30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM). 7. The exposure of the neurons with low-sodium, low-calcium solutions reversibly reduced the depolarizing/inward effects of anoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201411 TI - Contribution of a slowly inactivating potassium current to the transition to firing of neostriatal spiny projection neurons. AB - 1. Neostriatal spiny projection neurons display a prominent slowly depolarizing (ramp) potential and long latency to spike discharge in response to intracellular current pulses. The contribution of a slowly inactivating A-current (IAs) to this delayed excitation was investigated in a neostriatal slice preparation using current pulse protocols incorporating information based on the known voltage dependence, kinetics, and pharmacological properties of IAs. 2. Depolarizing intracellular current pulses evoked a slowly developing ramp potential that could last for seconds without reaching steady state and continued until either the pulse was terminated or spike threshold was reached. The slope of the ramp potential was dependent on the level of depolarization achieved by the membrane, and the apparent activation threshold for this ramp depolarization was approximately -65 mV. 3. Application of low concentrations of 4-aminopyridine (4 AP, 30-100 microM) or dendrotoxin (DTX, 30 nM), which are known to selectively block IAs, reduced both the slope of the ramp potential and the latency to first spike discharge. As has been described previously, blockade of inward Na+ and Ca2+ currents with tetrodotoxin (TTX, 1 microM) and cadmium (400 microM) also reduced the slope of the ramp depolarization. 4. A conditioning-test pulse protocol was used to examine the voltage dependence of inactivation of the ramp potential and long first spike latency. In the absence of a conditioning pulse, the test pulse evoked a slowly rising ramp potential and a spike with a long latency to discharge. A conditioning depolarization to approximately -60 mV decreased the slope of the ramp potential and the latency to first spike discharge evoked by the test pulse. A conditioning hyperpolarization to potentials below -100 mV, increased first spike latency. Application of a low concentration of 4-AP (100 microM) abolished the influence of prior membrane potential on the slope of the ramp depolarization and the latency to first spike discharge. 5. The kinetics of recovery from inactivation of the 4-AP-sensitive current were studied in the presence of TTX and cadmium by depolarizing cells to approximately -50 mV and then stepping to approximately -90 mV for increasing periods of time (0.5-5.0 s) before delivering a test pulse. The amplitude of the test pulse response decreased as a function of the hyperpolarizing step duration. When the test pulse response amplitudes were plotted against the hyperpolarizing step duration, the points reflected an exponential decay with an average time constant of 2.05 +/- 1.38 (SD) s.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201413 TI - Visual response properties of single neurons in the temporal pole of behaving monkeys. AB - 1. The responses of single neurons in the anterior part of the temporal cortex in monkeys, mainly the temporopolar cortex, area 36, and the most anterior part of area TE of von Bonin and Bailey (1947) (these areas were designated here as the temporal pole), were examined during the performance of a visual recognition memory task. The visual stimulus (sample stimulus) was presented when the monkey pressed a lever. The same sample stimulus was presented one to four times and, thereafter, a new stimulus was presented. The monkeys were trained to discriminate the new stimulus from the sample stimulus and to release the lever in response to the new stimulus. We used colored photographs of natural objects (human faces, monkeys, foods, and non-food objects) as complex visual stimuli or computer-generated two-dimensional shapes (a red square, a green circle, etc.) as simple visual stimuli. 2. In total, the activity of 311 neurons was recorded, and 225 of these responded to at least one visual stimulus. All visually responsive neurons were located in the ventral part of the temporal pole including the banks of the superior temporal sulcus. 3. The relationship between the monkey's eye movements and visual responses was investigated. Visual response properties, such as the number of spikes, onset latency, and response duration, were stable regardless of the monkey's eye positions and movements if the eyes were directed to the display. We also examined the receptive field property of neurons (n = 3). The neurons tested in the temporal pole tended to have a large receptive field (24 x 24 degrees). 4. The neurons tended to respond to different stimuli in different magnitudes. In each case, the maximal responses were elicited by complex, colored photographs, whereas simple, two-dimensional colored shapes elicited little or no responses. In 21% of the cases (47/225), the magnitude of the maximal response was significantly larger than for any of the other responses. 5. An achromatic version of the stimulus that induced the maximal response was tested in 53 neurons. About 80% of the neurons (41/53) responded to the achromatic stimulus at a magnitude that was not significantly different from the response to the original stimulus. In 12 neurons, the removal of color did significantly decrease the magnitude of the response. When other colors were tested, 3 of 9 neurons were found to code for color. 6. In 21 of these 53 neurons, a portion (the left-, right-, upper-, or lower-half) of the stimulus was also tested.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201412 TI - Ca(2+)-dependent non-NMDA receptor-mediated synaptic currents in ischemic CA1 hippocampal neurons. AB - 1. The changes in excitatory postsynaptic currents (EPSCs) after transient cerebral ischemia were studied using whole-cell recording from CA1 pyramidal neurons in gerbils. In 64% (18 of 28) neurons recorded 1.5-3 days after ischemia, EPSCs showed a markedly slowed time course that was never seen in normal control neurons. 2. The slow EPSCs were not affected by an N-methyl-D-aspartate (NMDA) receptor antagonist [DL-2-aminophosphonovalerate (APV); 100 microM] but were abolished by a non-NMDA receptor antagonist [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); 10 microM], indicating that the slow EPSCs were mostly composed of non NMDA current. 3. The slow non-NMDA EPSCs had rise times ranging from 1.2 to 7.3 ms and decay time constants between 11.5 and 56.3 ms. In normal neurons the rise time of the non-NMDA component of EPSCs ranged from 1.6 to 7.5 ms and the decay time constants ranged from 4.9 to 27.3 ms. 4. The reversal potential of the slow EPSCs in ischemic neurons was not changed by replacing 50% of the NaCl in the external solution with sodium isethionate. Bath application of 4-acetamido-4' isothiocyanatostilbene-2,2'-disulfonic acid (SITS; 100 microM) had no effect on the slow EPSCs. Therefore Cl- current is not responsible for the slow EPSCs. 5. When external Ca2+ concentration was reduced to half of control, the decay time constant of the slow EPSCs decreased to 50 +/- 25%, mean +/- SD. In addition, bath application of a cell-permeable Ca2+ chelator, 1,2-bis(o-aminophenoxy)ethane N,N,-N',N'-tetraacetyl,tetr aacetoxymethyl ester(BAPTA-AM), reduced the decay time constant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201414 TI - Inertial representation of angular motion in the vestibular system of rhesus monkeys. I. Vestibuloocular reflex. AB - 1. The spatial organization of the vestibuloocular reflex (VOR) was studied in six rhesus monkeys by applying fast, short-lasting, passive head and body tilts immediately after constant-velocity rotation (+/- 90 degrees/s) about an earth vertical axis. Two alternative hypotheses were investigated regarding the reference frame used for coding angular motion. 1) If the vestibular system is organized in head-centered coordinates, postrotatory eye velocity would decay invariably along the direction of applied head angular acceleration. 2) Alternatively, if the vestibular system codes angular motion in inertial, gravity centered coordinates, postrotatory eye velocity would decay along the direction of gravity. 2. Horizontal VOR was studied with the monkeys upright. Pitch (roll) tilts away from upright elicited a transient vertical (torsional) VOR and shortened the time constant of the horizontal postrotatory slow phase velocity. In addition, an orthogonal torsional (after pitch tilts) or vertical (after roll tilts) response gradually built up. As a result, the eye velocity vector transiently deviated in the roll (pitch) plane and then gradually rotated in the same direction as gravity in the pitch (roll) head plane until the orthogonal component reached a peak value. Subsequently, the residual postrotatory eye velocity decayed along a line parallel to gravity. 3. The time constant of the horizontal postrotatory response was maximal in upright position (21.5 +/- 5.7 s, mean +/- SD) and minimal after tilts to prone (3.8 +/- 0.7 s), supine (4.5 +/- 1.2 s), and ear-down (5.2 +/- 1.6 s) positions. A similar dependence on head orientation relative to gravity characterized the dynamics of the resultant eye velocity vector in the pitch and roll planes. 4. Torsional VOR was studied with the monkeys in supine or prone position. Pitch (yaw) tilts from the supine or prone position toward upright (ear-down) position elicited a transient vertical (horizontal) VOR and shortened the time constant of the torsional postrotatory response while a horizontal (vertical) orthogonal component slowly built up. As a result the eye velocity vector gradually rotated in the pitch (yaw) plane until the orthogonal component reached a peak value. Subsequently residual postrotatory eye velocity decayed along a line parallel to gravity. 5. The time constant of the torsional postrotatory response in supine/prone positions was 16.5 +/- 6.8 s. After tilts from supine/prone positions toward upright position, time constants decreased and were minimal after tilts to upright position (2.7 +/- 0.7 s).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201415 TI - Frontal eye field activity preceding aurally guided saccades. AB - 1. We studied neuronal activity in the monkey's frontal eye field (FEF) in conjunction with saccades directed to auditory targets. 2. All FEF neurons with movement activity preceding saccades to visual targets also were active preceding saccades to auditory targets, even when such saccades were made in the dark. Movement cells generally had comparable bursts for aurally and visually guided saccades; visuomovement cells often had weaker bursts in conjunction with aurally guided saccades. 3. When these cells were tested from different initial fixation directions, movement fields associated with aurally guided saccades, like fields mapped with visual targets, were a function of saccade dimensions, and not the speaker's spatial location. Thus, even though sound location cues are chiefly craniotopic, the crucial factor for a FEF discharge before aurally guided saccades was the location of auditory target relative to the current direction of gaze. 4. Intracortical microstimulation at the sites of these cells evoked constant-vector saccades, and not goal-directed saccades. The direction and size of electrically elicited saccades generally matched the cell's movement field for aurally guided saccades. 5. Thus FEF activity appears to have a role in aurally guided as well as visually guided saccades. Moreover, visual and auditory target representations, although initially obtained in different coordinate systems, appear to converge to a common movement vector representation at the FEF stage of saccadic processing that is appropriate for transmittal to saccade-related burst neurons in the superior colliculus and pons. PMID- 8201416 TI - Transient changes in intracellular calcium associated with a prolonged increase in excitability in neurons of Aplysia californica. AB - 1. Transient stimulation of an afferent input to the bag cell neurons of Aplysia californica triggers a 30-min period of spontaneous firing termed the afterdischarge. Measurement of free calcium ion concentrations using calcium sensitive electrodes revealed a biphasic pattern of elevation of intracellular calcium levels during the afterdischarge. Basal calcium levels at the soma were found to rise rapidly during afferent stimulation and then to decline before the onset of spontaneous firing. This early peak in intracellular calcium was followed by a slower, transient elevation of calcium levels during the period of rapid firing that occurs in the first few minutes of afterdischarge. Stimulation of clusters of bag cell neurons in a calcium-free external medium failed to trigger afterdischarge and produced no changes in basal intracellular calcium levels. 2. When calcium ions in the external medium were replaced by barium ions, stimulation of clusters of bag cell neurons triggered afterdischarges that were characterized by long-duration action potentials. Intracellular calcium levels during these afterdischarges rose slowly over the first few minutes of spontaneous firing. Because calcium-sensitive microelectrodes do not respond to barium ions, these data suggest that stimulation of afterdischarge triggers calcium release from an intracellular compartment. 3. During afterdischarges in barium-containing external media, each broadened action potential produced a discrete transient elevation of intracellular calcium levels. A similar effect was observed in isolated bag cell neurons in primary culture when action potentials were stimulated by depolarizing current pulses in a barium-containing medium. These data suggest that, under these conditions, individual action potentials trigger the release of intracellular calcium from some intracellular pool. PMID- 8201417 TI - Dopamine modulation of GABAC receptor function in an isolated retinal neuron. AB - 1. Dopamine modulation of gamma-aminobutyric acid (GABA)-elicited currents was studied in cone horizontal cells acutely isolated from the catfish retina using the whole-cell patch-clamp technique. 2. GABA puffs elicited both a GABAC current and a transporter current. Dopamine (10 microM) in the bath selectively reduced the GABAC receptor current without affecting the GABA transporter current. 3. This effect of dopamine was mimicked by the D1 agonist SKF38393 (25 microM) and an adenylyl cyclase activator forskolin (20 microM) but blocked by the dopamine antagonist haloperidol (30 microM). 4. These findings provide the first evidence for dopamine modulation of GABA receptor function in the vertebrate nervous system. In the intact retina, dopamine may modulate GABA-mediated chemical coupling and autofeedback in horizontal cells. PMID- 8201418 TI - Task dependent patterns of muscle activation at the shoulder and elbow for unconstrained arm movements. AB - 1. Six subjects performed three series of pointing tasks with the unconstrained arm. Series one and two required subjects to move as fast as possible with different weights attached to the wrist. The first required flexion at both shoulder and elbow joints. The second required shoulder flexion and elbow extension. The third series required flexion at both joints and subjects were intentionally instructed to vary movement speed. These three pointing tasks were selected as the simplest progression from single to multiple degree of freedom movements in which different patterns of motoneuron excitation are required depending on whether movements are made against different loads or at different intended speeds. 2. Changes in load and changes in intended speed both produced systematic but different changes in the patterns of muscle activity and joint torque in both the elbow and shoulder muscles. These patterns are the same found during constrained, single-joint elbow flexion movements. The changes are expressed in the rates of rise, durations, and latencies of the electromyographic (EMG) bursts and in the rates of rise of torque that have specific dependencies based on the force requirements of the task. 3. A consistent, almost linear relationship is observed between muscle torque at the shoulder and at the elbow for all three tasks. Similar systematic changes were not seen in the kinematic description of joint angles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201419 TI - Primate frontal eye field activity during natural scanning eye movements. AB - 1. As we scan an image, saccadic eye movements direct our vision to features that attract our attention. Although it is likely that the frontal eye field (FEF) cortex is an important component of the system generating those movements, most studies of FEF neuronal activity have relied upon visuomotor tasks where the experimental subjects are constrained to look from one spot of light to another. In this study, single-unit activity was recorded in the FEF while monkeys freely scanned a variety of projected images, and that activity was compared with activity evoked during conventional visuomotor tasks. 2. FEF neurons with visual activity in conventional tasks increased their activity during scanning when a portion of the image within their receptive field was targeted for the next saccade, but decreased their activity when a target was chosen outside of the receptive field. 3. FEF neurons with movement-related activity during conventional tasks were also active in association with saccades made during scanning. 4. Visual and movement activity were also studied by creating a task that approximated the conditions during the scanning paradigm (rescan task). This was done by superimposing a moveable spot of light onto the image that had been scanned, and rewarding the monkey for following the light as it recreated the original scan's spatial and temporal pattern of eye fixations. In contrast to the visual activity of neurons during the scanning paradigm, visual activity during the rescan task was unaffected by portions of the image within the cell's receptive field, but increased in response to the appearance of the target light.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201420 TI - Acutely isolated neurons of the rat globus pallidus exhibit four types of high voltage-activated Ca2+ current. AB - 1. Large, projection-like neurons from the adult (> 3 wk post-natal) rat globus pallidus (GP) were acutely isolated and subjected to whole-cell voltage-clamp (n = 37). Ca2+ currents were isolated pharmacologically in cells with whole-cell capacitances of 15-34 pF. 2. With 5 mM Ba2+ as a charge carrier, whole-cell currents began to activate near -40 mV and peaked near 0 mV. Based on activation threshold and inactivation kinetics, currents appeared to be of the high-voltage activated type. 3. Cd2+ blocked whole-cell currents with an IC50 near 2 microM. Currents activated at negative potentials were not relatively resistant to Cd2+, supporting the inference that low-voltage-activated currents were not prominent in these neurons. 4. The dihydropyridine, L-channel antagonist, nifedipine (5 microM), reduced peak current by 21 +/- 4% (SD) (n = 10). The dihydropyridine agonist, BayK 8644 (1-2 microM) enhanced peak current and slowed current deactivation (n = 4). 5. The N-channel antagonist, omega-conotoxin GVIA (omega CgTx, 2 microM) blocked 25 +/- 7% of the peak whole-cell current (n = 10). The blocks produced by omega-CgTx and nifedipine were additive, blocking an average of 46 +/- 8% of the current (n = 10). 6. The current resistant to the selective N and L-channel antagonists was partially blocked by the P-channel antagonist omega-agatoxin IVA (omega-AgTx, 100 nM). omega-AgTx blocked about one-half of the current not attributable to N- and L-type channels (22 +/- 5% of the total current, n = 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201421 TI - Modulation of preparatory neuronal activity in dorsal premotor cortex due to stimulus-response compatibility. AB - 1. Neuronal activity was recorded in the dorsal premotor cortex (PMd) of two monkeys performing a multidirectional, instructed-delay (ID) reaching task in which visuospatial cues signaled the direction of movement either congruent with the instruction cue ("direct-delay" trials, DD) or redirected 180 degrees opposite to the cue ("redirected-delay" trials, RD). Therefore, this task had two degrees of stimulus-response (S-R) compatibility because in one-half of the trials the spatial attributes of the visual cue were incongruent with those of the intended movement. 2. The majority of PMd cells discharged both at short latency to the RD or DD cues and subsequently with sustained activity during the remaining ID period (IDP). The earliest responses (< 250 ms) in both DD and RD trials covaried with cue location and so could be either a "visuospatial" response or a neuronal correlate of the selection of action with highest S-R compatibility, namely move to the stimulus. In contrast, later IDP activity usually covaried with the direction of movement signaled by the cues, independent of their spatial location, supporting the hypothesis that IDP discharge in PMd ultimately encodes attributes of intended reaching movements. PMID- 8201422 TI - Eye movements modulate activity in hippocampal, parahippocampal, and inferotemporal neurons. AB - 1. Inferotemporal, hippocampal, and parahippocampal units were recorded while monkeys were alert (as judged by eye movements) but resting, in both light and dark. 2. Spontaneous saccadic eye movements produced significant changes in unit activity for 108 of 308 cells. This activity is shown to be extraretinal either because it occurred in complete darkness or because of its timing relative to the eye movement. 3. The total saccadic modulation in the ventral temporal lobe is estimated to be over ten million action potentials. PMID- 8201423 TI - Variant firing patterns in rat hippocampal pyramidal cells modulated by extracellular potassium. AB - 1. The distribution of distinctive firing modes within the population of CA1 pyramidal cells and their modulation by the extracellular concentration of potassium ([K+]o) were investigated with intracellular recordings in rat hippocampal slices. 2. Pyramidal cells were injected with long (> 250 ms) and brief (3-5 ms) positive current pulses of increasing intensity. In normal [K+]o (3.5 mM), most cells (38 of 46 cells; 83%) were regular spiking neurons (generating accommodating trains of independent action potentials during long depolarizations and a single spike in response to brief stimuli). The remaining pyramidal cells (8 of 46; 17%) displayed differential tendencies to generate stereotyped clusters of action potentials, or bursts, according to which they were grouped into three subsets of endogenous bursters: grade I, bursting only when stimulated with long depolarizing current pulses (6 of 46; 13%); grade II, bursting also in response to brief stimulation (1 of 46; 2%); grade III, bursting also spontaneously even in absence of synaptic transmission (1 of 46; 2%). 3. Raising [K+]o from 3.5 to 7.5 mM (high [K+]o) significantly reduced resting membrane potential and input impedance but did not change the threshold potential for eliciting an action potential. 4. Raising [K+]o to 7.5 mM reversibly converted many regular spiking cells to bursters. Likewise, the burst tendency of normally bursting pyramidal cells increased to a higher grade in high [K+]o. Consequently, the fraction of bursters in high [K+]o (17 of 41 cells; 42%) was approximately 2.5-fold higher than in normal [K+]o and their differential distribution was shifted toward higher grades of bursting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201424 TI - Single-channel properties of high- and low-voltage-activated calcium channels in rat pituitary melanotropic cells. AB - 1. Single-channel properties of voltage-dependent calcium channels were investigated in rat melanotropes in short-term primary culture. Unitary currents were resolved using the cell-attached configuration. 2. Depolarizations higher than -50 mV activated a population of 8.1-pS calcium channels [low-voltage activated (LVA)]. The LVA channel ensembles displayed a monoexponential time course of inactivation and a sigmoidal time course of activation fitted best by an m2h Hodgkin-Huxley-type model. Microscopic kinetic analysis suggested that at least one open state, two closed states, and one inactivated state are involved in channel gating. 3. At potentials positive to -20 mV a second class of calcium channels was activated with a conductance of 24.7 pS [high-voltage activated (HVA)]. HVA channels display different gating modes. Gating with high open probability (mode 2) and low open probability (mode 1) as well as blank traces (mode 0) are observed. The HVA channels were heterogeneous with respect to their inactivation properties. Ensembles that decayed entirely during a 300-ms test pulse as well as nondecaying ensembles were observed. Both HVA channel subtypes displayed sigmoidal activation, which was fitted by an m2 model. Microscopic kinetic analysis suggested that at least one open state and two closed states are involved in mode two gating of both HVA channel subtypes. 4. Depolarizing prepulses did not recruit or facilitate calcium channel activity in response to a test pulse, but inactivating HVA channel activity was strongly reduced. Depolarizing prepulses (+50 mV) did not affect the probability of opening of the noninactivating HVA channel. 5. The voltage dependence and kinetics of the LVA as well as both HVA channels are in good agreement with previously published data on the properties of the various calcium current components derived from whole-cell recordings of rat melanotropes. The data suggest that a T-type as well as two L type channels (an inactivating and noninactivating channel) underlie the calcium current in these cells. PMID- 8201425 TI - Neuronal selectivities to complex object features in the ventral visual pathway of the macaque cerebral cortex. AB - 1. To infer relative roles of cortical areas at different stages of the ventral visual pathway, we quantitatively examined visual responses of cells in V2, V4, the posterior part of the inferotemporal cortex (posterior IT), and the anterior part of the inferotemporal cortex (anterior IT), using anesthetized macaque monkeys. 2. The critical feature for the activation was first determined for each recorded cell by using a reduction method. We started from images of three dimensional complex objects and simplified the image of effective stimuli step by step by eliminating a part of the features present in the image. The simplest feature that maximally activated the cell was determined as the critical feature. The response to the critical feature was then compared with responses of the same cell to a routine set of 32 simple stimuli, which included white and black bars of four different orientations and squares or spots of four different colors. 3. Cells that responded maximally to particular complex object features were found in posterior IT and V4 as well as in anterior IT. The cells in posterior IT and V4 were, however, different from the cells in anterior IT in that many of them responded to some extent to some simple features, that the size of the receptive field was small, and that they intermingled in single penetrations with cells that responded maximally to some simple features. The complex critical features in posterior IT and V4 varied; they consisted of complex shapes, combinations of a shape and texture, and combinations of a shape and color. 4. We suggest that local neuronal networks in V4 and posterior IT play an essential role in the formation of selective responses to complex object features. PMID- 8201426 TI - ATP-induced inward current in neurons freshly dissociated from the tuberomammillary nucleus. AB - 1. Neurons in the tuberomammillary nucleus (TMN), which are considered to be histaminergic, were dissociated and their response to extracellularly applied ATP was investigated in the nystatin-perforated patch recording mode under voltage clamp condition. 2. ATP induced a sustained inward current that was slowly desensitized at a holding potential of -60 mV. 3. The ATP response increased in a concentration-dependent manner. The half-maximum concentration (EC50) was 44 microM and the Hill coefficient was 1.8. 4. The potency of ATP analogues was in the order of ATP > or = 2-methylthio-ATP >> alpha, beta-methylene ATP > or = ADP. Neither adenosine nor AMP induced any response. The results suggest that the purinergic receptor in TMN neurons is P2y. 5. The current-voltage relationship for the 100 microM ATP showed a significant inward rectification at a potential more positive than -20 mV in an external solution with 150 mM Na+, but a significant rectification current was not observed in an external solution with 150 mM Cs+. The change in the reversal potential of the ATP response (EATP) to a 10-fold change of extracellular Na+ concentration was 56 mV, indicating that the ATP-induced current is highly selective for Na+ over Cl-. 6. The permeability ratio for cations was Na+:Li+:K+:Rb+: Cs+:Ca2+ = 2.16:1.36:1.68:1.54:1:2.55, indicating that the ATP-induced current is passing through the ligand-gated nonselective cation channel. 7. These results suggest that ATP has an excitatory effect on the TMN neurons by opening nonselective cation channels. PMID- 8201427 TI - In vivo measurement of human wrist extensor muscle sarcomere length changes. AB - 1. Human extensor carpi radialis brevis (ECRB) sarcomere length was measured intraoperatively in five subjects using laser diffraction. 2. In a separate cadaveric study, ECRB tendons were loaded to the muscle's predicted maximum tetanic tension, and tendon strain was measured to estimate active sarcomere shortening at the expense of tendon lengthening. 3. As the wrist joint was passively flexed from full extension to full flexion, ECRB sarcomere length increased from 2.6 to 3.4 microns at a rate of 7.6 nm/deg joint angle rotation. Correcting for tendon elongation during muscle activation yielded an active sarcomere length range of 2.44 to 3.33 microns. Maximal predicted sarcomere shortening accompanying muscle activation was dependent on initial sarcomere length and was always < 0.15 microns, suggesting a minimal effect of tendon compliance. 4. Thin filament lengths measured from electron micrographs of muscle biopsies obtained from the same region of the ECRB muscles were 1.30 +/- .027 (SE) microns whereas thick filaments were 1.66 +/- .027 microns long, suggesting an optimal sarcomere length of 2.80 microns and a maximum sarcomere length for active force generation of 4.26 microns. 5. These experiments demonstrate that human skeletal muscles can function on the descending limb of their sarcomere length-tension relationship under physiological conditions. Thus, muscle force changes during joint rotation are an important component of the motor control system. PMID- 8201428 TI - Defense reaction in the pond snail Planorbis corneus. I. Activity of the shell moving and respiratory systems. AB - 1. In the intact pond snail Planorbis corneus, tactile or electrical stimulation of the skin evoked a biphasic general defense reaction. A weak stimulation evoked only the first phase of the reaction, represented as a fast pulling of the shell towards the head. With stronger stimulation, this phase was followed by the second phase that was comprised of three components: detachment from the substrate, slow retraction of the body into the shell, and letting out of air from the lung through the pneumostome. 2. About 70 motor neurons (MNs) of the columellar muscle have been revealed in different ganglia by means of their cobalt back-filling through the cut columellar nerve. A complicated pattern of electrical coupling was found for different groups of MNs. Excitation of individual MNs, evoked by current injection, resulted in contraction of the columellar muscle (CNS-columellar muscle preparation). The strongest contraction was evoked by the cerebral MNs; fast small contraction by the parietal MNs; and slow, long-latency contraction, by the pedal MNs. 3. In the same preparation, electrical stimulation of the cutaneous (lip) nerve evoked biphasic contraction of the columellar muscle (a first phase lasting approximately 3 s, and a second phase of up to 1 min). The temporal pattern of this response was similar to that of the defense reaction in the intact animal. A weak stimulation evoked only the first phases of the reaction, while a stronger stimulation evoked both phases. The amplitude of both the first and the second phase was graded with the strength of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201429 TI - Defense reaction in the pond snail Planorbis corneus. II. Central pattern generator. AB - 1. In the isolated CNS of the pond snail Planorbis corneus, spontaneous bursts of activity in the motor neurons (MNs) supplying the columellar muscle were occasionally observed. The biphasic pattern of this activity, with a shorter (3-5 s) initial burst and longer (20-40 s) subsequent burst, was similar to that of the motor output during the general ("whole-body") defense reaction. In preparations consisting of the CNS isolated with the columellar muscle or with the lung, spontaneous biphasic contractions of the muscle as well as openings of the pneumostome with a temporal pattern characteristic of the defense reaction were observed. These findings demonstrated that the efferent pattern of the defense reaction in the snail is, to a large extent, produced by a special neuronal mechanism (the central pattern generator, CPG) triggered by the sensory input, rather than generated by ongoing processing of sensory input. The CPG consists of two components responsible for generation of two phases of the defense reaction. A characteristic feature of the CPG is that the magnitude of its response depends in a graded fashion on the strength of the initial stimulus. 2. In the pleural ganglia there are at least two electrically connected interneurons (DRN1s) that play an important role in generation of the first phase of the defense reaction. Processes of the DRN1s form a ring passing through all (except pedal and buccal) ganglia. The DRN1s received an excitatory input when a peripheral nerve was stimulated. They generated action potentials of long (0.2-2 s) duration. The DRN1 from the right ganglion was studied in more detail.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201430 TI - Defense reaction in the pond snail Planorbis corneus. III. Response to input from statocysts. AB - 1. In the intact pond snail Planorbis corneus, a rapid tilt in any plane evoked a defense reaction consisting of a fast movement of the shell towards the head, shortening of the foot, inhibition of locomotion and of rhythmical feeding movements. This reaction was similar to the first phase of the general defense reaction of Planorbis to cutaneous stimulation. 2. A method has been developed for inclination of the isolated CNS in space (up to 90 degrees) and simultaneous intracellular recordings from different neurons. 3. The statocyst receptor cells (SRCs) responded both phasically and tonically to the tilt. The SRCs differ in their spatial zones of sensitivity. 4. Essential manifestations of the defense reaction to the input from statocysts could be observed in the in vitro preparation of the CNS isolated with statocysts. Both tilting of the CNS and electrical stimulation of individual SRCs elicited an excitatory response in numerous neurons from different ganglia, including motor neurons (MNs) of the columellar muscle. This response was of "all-or-none" nature, and could be evoked by electrical stimulation of any SRC. The response was followed by a long (10-20 s) period of refractoriness. 5. Activation of SRCs resulted also in excitation of the giant dopaminergic cell in the left pedal ganglion (related to the control of respiration), in inhibition of the feeding rhythm generator, and in inhibition of the pedal neurons responsible for activation of the ciliary locomotor system. 6. Combined stimulation of two inputs able to evoke a defense reaction, i.e., those from the statocyst and from cutaneous nerve, revealed a strong interdependence of their central effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201431 TI - Binaural organization of primary auditory cortex in the ferret (Mustela putorius). AB - 1. The distribution of binaural responses within the ferret's primary auditory cortex was determined by standard microelectrode mapping techniques. Single and multiple unit responses were recorded from the middle ectosylvian gyrus of barbiturate-anesthetized animals with tungsten microelectrodes (1.2-1.8 M omega) inserted into the brain perpendicular to the cortical surface. The characteristic frequency (CF) and binaural response characteristics were determined for each point sampled. 2. Gated pure tones were delivered independently to the two ears through a sealed sound system, and binaural response types were determined by comparison of evoked activity for monaural and binaural stimulation. Most binaural responses fell into one of three major groups: binaural summation (EE/F), binaural suppression (EO/I), or mixed binaural summation and suppression. 3. The neurons tended to be grouped together on the basis of their binaural response properties. Zones of binaural summation and suppression extended across the surface of the middle ectosylvian gyrus and intersected with regions of sound frequency representation. 4. Particular attention was paid to the distribution of binaural responses within isofrequency contours in the ferret's primary auditory cortex (AI). Along the length of each isofrequency contour, areas of EE/F alternated with areas of EO/I. The summation areas were typically between 0.5 and 0.7 mm wide. Single neurons with mixed binaural response properties were frequently found between groups of EE/F and EO/I cells. The mixed responses appeared to mark a transition in location between zones of summation and suppression responses. 5. The distribution of interaural intensity difference (IID) thresholds was also examined along the length of isofrequency contours. No systematic relation was found between IID threshold and the distance along an isofrequency contour. PMID- 8201432 TI - Neuronal circuits associated with the output of the dorsal cochlear nucleus through fusiform cells. AB - 1. Intracellular recordings were made from 21 anatomically identified fusiform cells in the dorsal cochlear nucleus (DCN) of mice in slices. The aim of the experiments was to dissect the synaptic responses to shocks of the auditory nerve to correlate functional characteristics with the different classes of synaptic inputs. 2. When depolarized from rest (-57 +/- 5 mV) with current pulses, fusiform cells fired regular, overshooting action potentials that were followed by two undershoots. The frequency of firing increased with the strength of injected current by between 100 and 300 spikes/s/nA. The current-voltage relationship rectified between 10 and 15 mV below the resting potential. The slopes of current-voltage relationships of fusiform cells in the range between the resting potential and 10 mV hyperpolarization indicated an average input resistance of 86 +/- 37 M omega. 3. In each of the labeled fusiform cells frequent, spontaneous inhibitory postsynaptic potentials (IPSPs) were recorded singly or in bursts. Some, but not all, IPSPs were preceded by a slowly rising excitatory postsynaptic potential (EPSP). The temporal association of spontaneous EPSPs and IPSPs suggests that they are driven by a common source, possibly granule cells. 4. Shocks to the auditory nerve evoked synaptic responses consisting of early (1 to approximately 10 ms) and late (approximately 10 to 100 ms) components. 6,7-Dinitroquinoxaline-2,3-dione (DNQX) at 20 to 40 microM eliminated all detectable excitation and all late IPSPs. Late bursts of IPSPs, therefore, are mediated through a polysynaptic pathway that includes a DNQX sensitive stage. Strong shocks to the nerve root elicited single monosynaptic IPSPs, indicating that inhibitory interneurons have processes close to the auditory nerve. Strychnine at 0.5 microM eliminated all detectable inhibition. 6. Cuts through the posteroventral cochlear nucleus (PVCN), which severed the descending branches of auditory nerve fibers, eliminated early EPSPs and IPSPs leaving late, slowly rising EPSPs and bursts of IPSPs in responses to shocks of the auditory nerve. Late, slowly rising EPSPs and bursts of IPSPs, as well as monosynaptic IPSPs, could also be evoked by stimulating the anteroventral cochlear nucleus (AVCN). 7. Focal applications of glutamate evoked excitation and inhibition from many parts of a slice, with patterns varying among cells, indicating that fusiform cells receive inputs through several groups of interneurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201433 TI - Changes in a postural strategy with inter-paw distance. AB - 1. The purpose of this study was to examine the effect of changing initial stance conditions on the postural response of the cat to horizontal plane translations of the support surface. Cats were trained to stand, unrestrained, on a moveable force platform. The platform was translated linearly in each of 16 directions in the horizontal plane, with a ramp-and-hold displacement. The animal's response was quantified in terms of the forces exerted at the ground. The trajectory of the center of mass (CoM) was computed from the forces. 2. Stance length was varied along the longitudinal (sagittal) axis by adjusting the distance between the forepaw and hindpaw force plates. Translation perturbations of the platform were recorded at stance distances varying from 66 to 110% of the preferred stance distance. 3. Changing stance distance had a significant effect on the amplitude and direction of the active forces exerted by the cat both during quiet stance and during the response to platform translation. At long stance distances, each limb exerted a force outward, along the diagonals during quiet stance. The response to translation was characterized by an invariance in the direction of force exerted against the ground, a strategy that was described previously. At short stance distances, quiet stance forces were more laterally directed. The force constraint strategy was usually not observed for the response to translation. Nevertheless, the cats were equally effective at all stance distances in restoring the position of the center of mass after translation of the support surface. 4. There was no discrete boundary between the presence and absence of the force constraint, suggesting that the strategy for exerting forces against the support surface is characterized by a continuum of response, from a bimodal, or anisotropic distribution of force vectors on the one extreme, to a uniform, or isotropic distribution on the other. Arguments are developed to suggest that the force constraint strategy may be useful in stabilizing the vertebral column during the response to platform translation, to allow linear translation of the CoM rather than bending of the trunk. PMID- 8201434 TI - Regulation of cutaneous C-fiber heat nociceptors by nerve growth factor in the developing rat. AB - 1. Previous work has indicated that nerve growth factor (NGF) is an important factor for the development of nociceptive A-delta fibers. Here we asked if the availability of NGF during the first 2 wk of development can influence the phenotypic development of unmyelinated afferent C-fibers. 2. To do this, we treated newborn rats with antibodies to NGF from postnatal day (PND) 2-14, a treatment known not to lead to cell death, or with exogenous NGF (PND 0-14). Untreated litter mates served as controls. When the animals were mature (5-20 wk later), they were anesthetized (urethan, 1.25 g/kg ip) and single-unit recordings were made from sural nerve C-fibers in dorsal root filaments. To obtain an unbiased estimate of the physiological types present, an electrocutaneous search technique was employed to isolate the location of the putative receptive field of the C-fiber being studied within the sural nerve territory. This technique enabled us to acquire a sample of C-fibers that was unbiased by natural search stimuli which are often damaging to skin. 3. We found that the proportion of C fibers that could be driven by noxious heat and mechanical stimuli (C-mechanoheat fibers, C-MH) was reduced from 28% (11/40 fibers) of the sample in controls to 10% (3/31 fibers) in anti-NGF treated animals. The C-MH fibers appeared to have been replaced by a novel type of pressure receptor with an unusually low mechanical threshold (mean 0.86 +/- 0.58 compared with 13.0 +/- 8.3 g for control mechanonociceptors).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201435 TI - Monosynaptic and disynaptic connections in the utriculo-ocular reflex arc of the cat. AB - 1. Connections from the utricular (UT) nerve to motoneurons and interneurons in the ipsilateral abducens (AB) nucleus were studied in anesthetized and decerebrated cats. Bipolar electrodes were fixed on the left UT nerve under visual observation. The other branches of the vestibular nerve and the facial nerve were transected in the left inner ear. 2. Stimulation of the UT nerve evoked a small positive-negative (P/N) deflection and a negative (N1) potential in the vestibular nuclei, with mean latencies of 0.56 and 0.84 ms, respectively. In the AB nucleus a small P/N deflection with a mean latency of 0.72 ms was recorded, which was considered as a incoming volley of the UT nerve. 3. Excitatory postsynaptic potentials (EPSPs) were recorded from AB motoneurons with short latencies after UT nerve stimulation. They were classified into two types, M and D. M-type EPSPs, which followed repetitive high-frequency stimuli and were recorded from the majority of AB motoneurons, had latencies ranging from 0.9 to 1.2 ms. Double shocks to the UT nerve evoked EPSPs that had the same latency. It was suggested that the AB motoneurons had monosynaptic connections with the UT nerve. D-type EPSPs, which were recorded from most of the AB motoneurons, had slightly longer latencies ranging from 1.2 to 1.8 ms. They showed temporal facilitation when double shocks were provided to the UT nerve. They did not follow repetitive high-frequency stimuli (< or = 2.5-ms interval). It was suggested that D-type EPSPs were di-synaptically evoked via secondary vestibular neurons. Interneurons in the AB nucleus had the same characteristics as AB motoneurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201436 TI - Spinothalamic and spinohypothalamic tract neurons in the cervical enlargement of rats. I. Locations of antidromically identified axons in the thalamus and hypothalamus. AB - 1. Seventy-seven neurons in the cervical enlargement of rats anesthetized with urethan were initially antidromically activated using currents < or = 30 microA from the contralateral posterior thalamus. A goal of these experiments was to determine the course of physiologically characterized spinal axons within the diencephalon. Therefore, in 38 cases, additional antidromic mapping was done throughout the mediolateral extent of the diencephalon at multiple anterior posterior planes. 2. Electrolytic lesions marking the recording sites were recovered for 71 neurons. Thirty-one were located in the superficial dorsal horn (SDH); 39 were in nucleus proprius or the lateral reticulated area of the deep dorsal horn (DDH), and one was in the ventral horn. 3. Eight of 38 (21%) neurons that were tested for more anterior projections could only be antidromically activated with currents < or = 30 microA from sites in the contralateral posterior thalamus. Such neurons are referred to as spinothalamic tract (STT) neurons. Lesions marking the lowest threshold points for antidromic activation were located in or near the posterior thalamic group (Po). At more anterior levels, considerably higher currents were required for antidromic activation or it was not possible to activate the neurons with currents up to 500 microA. Four of these neurons were physiologically characterized and each responded preferentially to noxious mechanical stimuli (wide dynamic range, WDR). Each of the three neurons that were tested responded to noxious heat stimuli. These findings confirm anatomic studies that have shown that a number of STT axons terminate in Po and suggest that such axons that originate in the cervical enlargement carry nociceptive input from the upper extremity. 4. In 15 cases, electrode penetrations were made systematically throughout much of the contralateral ventrobasal complex (VbC). In 17 cases, penetrations were made throughout the intralaminar nuclei contralaterally, including the central lateral nucleus (CL). Surprisingly, only one of the examined axons was antidromically activated with low currents from CL and one from VbC, although both of these nuclei are known to receive sizeable inputs from the STT. 5. Many of the axons (27 of the 38 tested, 71%) that were initially antidromically activated from the contralateral posterior thalamus could also be antidromically activated with low currents (< or = 30 microA) and at increased latencies from sites located anteriorly in the contralateral hypothalamus. Such neurons are referred to as spinothalamic tract/spinohypothalamic tract (STT/SHT) neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201437 TI - Spinothalamic and spinohypothalamic tract neurons in the cervical enlargement of rats. II. Responses to innocuous and noxious mechanical and thermal stimuli. AB - 1. The goal of this study was to gather data that would increase our understanding of nociceptive processing by spinothalamic tract (STT) neurons that receive inputs from the hand and arm. Fifty neurons in the cervical enlargement of urethan-anesthetized rats were antidromically activated from the contralateral posterior thalamus. A stimulating electrode was moved systematically within an anterior-posterior plane in the thalamus until a point was located where the smallest amount of current antidromically activated the neuron. The antidromic thresholds at each of these lowest threshold points was < or = 30 microA; the mean antidromic threshold was 15.4 +/- 1.0 (SE) microA. Lowest threshold points were found primarily in the posterior thalamic group (Po), zona incerta, and in or near the supraoptic decussation. 2. The recording sites of 47 neurons were marked and recovered. Recording sites were located in the superficial dorsal horn (SDH, n = 15), deep dorsal horn (DDH, n = 31), and ventral horn (n = 1). Recording sites were located across the mediolateral extent of the SDH. Within the DDH, recording sites were concentrated laterally in nucleus proprius and dorsally in the lateral reticulated area. The locations of the recording points confirm previous anatomic descriptions of STT neurons in the cervical enlargement. 3. Cutaneous excitatory receptive fields were restricted to the ipsilateral forepaw or forelimb in 67% (10/15) of the neurons recorded in the SDH and 42% (13/31) of the neurons recorded in the DDH. Neurons having larger, more complex receptive fields were also commonly encountered. Thirty-three percent (5/15) of the neurons recorded in the SDH and 58% (18/31) recorded in the DDH had receptive fields that were often discontinuous and included areas of the ipsilateral shoulder, thorax, and head, including the face. 4. Innocuous and noxious mechanical stimuli were applied to the receptive field of each neuron. Fifty percent (25/50) responded to innocuous mechanical stimuli but responded at higher frequencies to noxious stimuli (wide dynamic range, WDR). Forty-four percent (22/50) responded only to noxious stimuli (high threshold, HT). Six percent (3/50) responded preferentially to innocuous stimuli (low threshold, LT). WDR and HT neurons were recorded in both the SDH and DDH, including nucleus proprius, an area not typically associated with nociceptive transmission at other levels of the cord. Sixty percent (9/15) of the units recorded in the SDH were classified as WDR neurons; the other 40% (6/15) were classified HT. Forty-eight percent (15/31) of the units recorded in the DDH were classified as WDR neurons and 42% (13/31) as HT.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201438 TI - African American women and their pregnancies. Introduction. PMID- 8201439 TI - Prenatal predictors of performance on the Brazelton Neonatal Behavioral Assessment Scale. AB - The present study presents a prospective analysis of the interrelationships among prenatal medical, nutritional (dietary and biochemical) and behavioral determinants of Brazelton performance. Previous researchers (Scanlon 1984, Lester and Brazelton 1984) have raised questions regarding the relative roles of medical factors, nutrition, ponderal index and other behavioral factors in neonatal performance on the BNBAS. Four hundred sixty-seven predominantly Black nulliparous women and their neonates in Washington, D.C. who were enrolled in the study by the 20th week of gestation were subjects. Results of univariate tests of significant (P < 0.01) association between independent variables and Brazelton clusters from scores measured on day 2 are presented. The 26 behavioral items were summarized into 6 clusters as done in similar studies by linearizing measures made on a curvilinear scale and taking the mean. The 6 behavioral clusters are habituation, motor, orientation, range of states, regulation of states, and autonomic. Results of 16 reflex tests are used to define a seventh reflex cluster. Independent variables included demographic, lifestyle, nutritional, medical, ponderal index, and psychosocial measures. Several psychosocial variables, including stress, anxiety and partner interaction were associated with the behavioral clusters. Nutritional variables were associated with BNBAS habituation, motor, orientation, reflex score and autonomic responses. An analysis of co-variance was performed to determine the joint effect of the above variables on the variation in the Brazelton performance on the seven cluster scores. Five of the seven models (orientation, motor, range of states, autonomic, and reflex scores) were significant predictors of the outcome variables. PMID- 8201440 TI - Maternal stress and pregnancy outcomes in a prenatal clinic population. AB - A two-fold decrease in the incidence of infant low birth weight, from 20.6% to 8.3%, occurred in Africa American women enrolled from 1985 to 1988 in this interdisciplinary research project conducted in an urban prenatal clinic. Nutritional, biochemical, medical, psychosocial, lifestyle, and environmental data were collected by trained Africa American interviewers. Several instruments were administered to the mother to specify the stress construct and assess body image, the social support network, and other psychosocial variables. The reduction in the incidence of low birth weight in an urban Africa American low income population admitted to the Howard University Hospital is attributed to the mediation of maternal stress by project personnel, in effect, providing an additional support system through the caring, sensitive environment provided by the project clinical staff, who met the women at each of their clinic-scheduled appointments. Women with a positive self attitude and higher self esteem were more likely to be delivered infants at term; the number of persons in the mother's social support network was directly correlated with her infant's gestational age. Maternal serum concentrations of the antioxidant vitamins, vitamin E and ascorbic acid, and the free radical scavenger, uric acid, were significantly correlated with serum folate and blood urea nitrogen. An hypothesis of low birth weight is presented. PMID- 8201441 TI - African American women and their pregnancies. Research papers from the program project: Nutrition, Other Factors and the Outcome of Pregnancy. PMID- 8201442 TI - Demographic profile, methodology, and biochemical correlates during the course of pregnancy. AB - This five-year prospective, observational study of urban women during their pregnancies was initiated in 1985 with the recruitment of women between the ages of 18 and 35 years in the prenatal clinics of Howard University Hospital and the District of Columbia Department of Human Services. The objective of the investigation was to characterize African American women by nutritional, biochemical, medical, sociocultural, psychological, lifestyle, and environmental parameters which could be used to formulate interventions to improve pregnancy outcomes. The women were all nulliparous, free of diabetes and abnormal hemoglobins, such as sickle cell disease, and no more than 28 weeks pregnant. During the early course of the study, it was apparent that 96% of the low income clinic patients had delivered infants of normal birth weight (> or = 2500 g), P = 0.001. Recruitment was then initiated at the District of Columbia General Hospital; women 16 and 17 years of age and at any gestational stage were included. This paper is the first in the series on African American women and their pregnancies. It will present the demographic characteristics of this regular cohort of 443 women who delivered live infants, the methodology used for biochemical, dietary, and psychosocial data sets, the mean values for infant gestational age, head circumference, body length, and birth weight from singleton births, and correlates of the mean values of biochemical variables for three trimesters of pregnancy with other biochemical parameters and those pregnancy outcomes. PMID- 8201443 TI - Multiple factors as mediators of the reduced incidence of low birth weight in an urban clinic population. AB - A five year prospective observational study was initiated in 1985 at Howard University to describe the nutritional, clinical, dietary, lifestyle, environmental, and socioeconomic characteristics of women who enrolled in the hospital prenatal clinic. The participants were nulliparous, between the ages of 18 and 35 years, free of diabetes and abnormal hemoglobins (sickle cell disease, thalassemia, and hemoglobin C), and had been admitted prior to the 29th week of gestation. During the three year period from 1985-1988, the incidence of low birth weight (LBW) in 239 deliveries to project participants was 8.3%, whereas that of women simultaneously enrolled in the prenatal clinic with the same eligibility requirements, but not recruited for the research project, was 21.9% (P = 0.001). The incidence of LBW in infants of African American women with these eligibility requirements who were delivered by private physicians but were not enrolled in the project, was 6.3%. The reduction in LBW of infants delivered to participants in this study is attributed to the enhanced social and psychological support by project staff during their pregnancies. The caring, sensitive demeanor of the research project staff may have empowered the participants to (a) give greater compliance (91 vs. 70%) in the ingestion of the routine physician prescribed vitamin/mineral supplement, which provided nutrients low (less than 70% of the 1989 RDAs) in their customary diets, such as folate, pyridoxine, iron, zinc, and magnesium and (b) show greater accountability in keeping prenatal clinic appointments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201444 TI - Dietary intakes, anthropometric measurements and pregnancy outcomes. AB - The relationships of maternal prenatal dietary intakes and anthropometric measurements to pregnancy outcomes were investigated in a prospective observational study of urban African American women. The 322 subjects, a subset of the 744 women recruited for the study using purposive sampling, were all nulliparous, free of diabetes mellitus and abnormal hemoglobins, and delivered term, singleton infants. Sociodemographic data and monthly quantitative 24-hour food recalls were collected by trained interviewers. Maternal anthropometric measurements were obtained from the subjects' hospital records. Pregnancy outcome data were obtained by physical examinations of the newborn infants by the project pediatrician. With the exception of vitamin C, average maternal dietary intakes were within the ranges of intakes obtained in previous studies. Mean intakes of protein, vitamins A and C, thiamin, riboflavin, and niacin exceeded the 1989 RDA, while those of food energy, vitamin B-6, folate, calcium, iron, magnesium, and zinc were below the RDA. Underweight prior to pregnancy and low pregnancy weight gains were found among 12.9% and 44.4% of the subjects respectively. Dietary intakes were not significantly correlated with pregnancy outcomes. Maternal anthropometric measurements significantly correlated with pregnancy outcomes included delivery weight, pregnancy weight gain, weekly weight gain, prepregnancy weight, net weight gain, height, prepregnancy body mass index, and % ideal prepregnancy body weight (P < 0.05). Using the stepwise selection procedure in multiple regression analysis, delivery weight, % ideal prepregnancy body weight, and prepregnancy body mass index were selected as being predictive of infant birth weight. It was concluded that anthropometric measurements were better nutritional predictors of pregnancy outcome than dietary intake. PMID- 8201445 TI - Biochemical profile of African American women during three trimesters of pregnancy and at delivery. AB - The data presented are the results from a prospective observational study which was conducted to investigate the effects of nutrition and other related factors on the outcome of pregnancy in nulliparous African American women 16-35 years old. Fasting blood samples were collected from the women during the first, second and third trimesters of pregnancy. At delivery, both maternal and cord samples were collected. Biochemical variables such as, serum folate, vitamin B12, ascorbic acid, vitamin E, ferritin, selected minerals as well as complete blood count (CBC) and red cell folate were analyzed in the blood samples. The concentrations of hematocrit, hemoglobin, white blood cells, red blood cells and vitamin B12 were below the reference non-pregnant ranges throughout gestation. Maternal concentrations of folate and vitamin E increased sequentially with increased gestational age. Serum ferritin, during the third trimester, declined to 58% of the first trimester concentration. Maternal levels of ferritin at delivery were one third of the values found in the infant (cord) sample. Cord levels of folate, ascorbic acid and vitamin B12 were higher than the concentrations in the maternal delivery samples. The data suggest that among this group of pregnant women, major physiological changes, such as plasma volume expansion which alters blood chemistry and maternal to fetal transfer of nutrients, were similar to the findings of other investigators. In this population however, the findings for serum and whole blood folate are contrary to those reported by other researchers, and the sequential increase in the maternal concentration of the vitamin during pregnancy could be attributed to the use of vitamin supplements. PMID- 8201446 TI - Pica in an urban environment. AB - The practice of pica, the compulsive ingestion of nonfood substances over a sustained period of time, was studied in 553 African American women who were admitted to prenatal clinics in Washington, D.C. Dietary, biochemical, and psychosocial correlates of the pica practices of a subset of this urban population are presented in this paper. Geophagia, compulsive eating of clay or dirt, was not observed in these women; pagophagia, or the ingestion of large quantities of ice and freezer frost, was self reported in 8.1% of the women, who consumed 1/2 to 2 cups a day from 1 to 7 days per week. Serum ferritin concentrations of pica women were significantly lower during the second and third trimesters of pregnancy; the average values for three trimesters of pregnancy for both ferritin and mean corpuscular hemoglobin were significantly lower in pica women than their nonpica counterparts (P = 0.0001 and P = 0.017, respectively). Although not significantly different, the iron (66 vs. 84% RDA) and calcium (60 vs. 75% RDA) contents of the diets of pica women were less those of nonpica women. Gestational age, body length, and body weight were not different, but head circumferences of infants delivered to pica women who consumed freezer frost and/or ice were smaller than those of nonpica women (P = 0.012). The hypothesis is presented that pica in African American women may be a mediator of stress, acting through the immune system. The size of the social support network of pica women was significantly less than that of nonpica women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201447 TI - Selected lifestyle practices in urban African American women--relationships to pregnancy outcome, dietary intakes and anthropometric measurements. AB - The relationships of selected lifestyle factors (cigarette smoking, consumption of alcoholic beverages, recreational drug use, and exercise during pregnancy), all self-reported, to pregnancy outcomes, dietary intake during pregnancy, and maternal anthropometric measurements, were investigated in a group of urban African American pregnant women. The 234 subjects were aged 16-35 years and were free of diabetes and abnormal hemoglobins. The lifestyle data were collected by trained interviewers during the subjects' prenatal clinic visits, and the dietary data by monthly, quantitative 24-hour food recalls conducted during these same visits. Maternal anthropometric measurements were obtained from the subjects' hospital records, and pregnancy outcome data during physical examinations of the newborn infants. Both cigarette smoking and drug use were associated with significantly lower mean birth weight, length, and head circumference, while exercise was associated with a significantly higher mean birth weight, and head circumference (P < 0.05). Drug use during pregnancy was associated with a significantly higher intake of vitamin C, and a significantly lower intake of iron; while women reporting drug use before pregnancy had significantly higher mean intakes of food energy, protein, total and saturated fat, and zinc. Prepregnancy weight, percent ideal prepregnancy body weight, prepregnancy body mass index, and delivery weight were significantly lower among those reporting drug use before pregnancy. Multiple regression analyses indicated that smoking explained a relatively small proportion of the variance in infant birth weight compared with delivery weight and percent of ideal prepregnancy body weight. PMID- 8201448 TI - Relationships of serum illicit drug concentrations during pregnancy to maternal nutritional status. AB - Findings reported are for a subset of African American subjects, residing in the urban area of Washington, D. C., who participated in a Program Project designed to study nutrition, other factors, and the outcome of pregnancy. Fasting blood samples, drawn during each trimester of pregnancy and at delivery, were screened for concentrations of cocaine, phencyclidine (PCP) and marijuana. Since substance abusers are expected to consume inadequate diets, these samples were also analyzed for serum folate, vitamin B12, ferritin and ascorbic acid. Data for these biochemical variables were compared for subjects whose serum values for drugs were either above or below the drug screening threshold concentrations established by ADAMHA/NIDA. Pearson's correlations were used to determine relationships between pregnancy outcome variables and maternal serum drug concentrations. Blood samples drawn at delivery showed higher maternal: cord ratios (mean +/- SEM) for marijuana (3.3 +/- 2.2) and PCP (2.9 +/- 1.0) than for cocaine (1.0 +/- 0.2). The subjects whose serum values were above the ADAMHA/NIDA ranges for marijuana, PCP and cocaine had concentrations of folate and ferritin that were significantly less than those of subjects with lower serum drug levels (P < or = 0.05). High maternal serum concentrations of illicit drugs were accompanied by a significant increase in leukocyte count (P < or = 0.05). The level of maternal cocaine during the third trimester was inversely correlated with birthweight (r = -0.29; n = 52; P = 0.038) and head circumference (r = 0.28; n = 52; P = 0.047).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201449 TI - Maternal low level lead and pregnancy outcomes. AB - We examined the relationship between the concentrations of blood lead and pregnancy outcomes in a subset of 349 African American women who enrolled in the program project, "Nutrition, Other Factors, and the Outcome of Pregnancy." Vitamin-mineral supplement users had significantly higher serum levels of ascorbic acid and vitamin E. Also, in supplement users, there were significantly lower mean concentrations of maternal blood lead. Inverse correlations were found between maternal levels of lead and the antioxidant vitamins, vitamin E and ascorbic acid. In addition, significant Pearson's correlations were observed between maternal blood lead levels and the following variables: positive correlations with calcium, phosphorus, mean corpuscular volume; inverse correlations with gestational age, Ponderal Index, infant orientation, and hematologic values. In the total subset, the three trimester sample means for maternal blood lead concentrations were not significantly different for mothers of infants who weighed less than 2500 g (low birth weight) and those who were delivered infants who weighed 2500 g or more. Clinically, nutrition may play a role in the reduction of potentially adverse effects from lead during pregnancy, i.e. protection of the fetus against lead toxicity and/or free radical damage through the antioxidant actions of vitamin E and ascorbic acid. Even when maternal blood lead levels are within the so-called "safe" range, maternal/use of a vitamin supplement supplying vitamin E and ascorbic acid during pregnancy may offer protection. PMID- 8201451 TI - Prenatal substance abuse and pregnancy outcomes among African American women. AB - Subjects in this prospective observational study were 467 nulliparous women, ages 16-35, recruited at the prenatal clinics of a university hospital and a public hospital. Using a purposive sampling approach, and entry questionnaire and a series of psychosocial instruments were administered throughout the pregnancy course to assess stress, anxiety, body image, self-esteem, pregnancy symptoms, locus of control, and partner's interaction. Several pregnancy outcome measures were determined after delivery. Brazelton neonatal behavioral assessments were performed two days after birth of infants delivered to the maternal subjects. Self-reported substance abuse data were obtained from the entry questionnaire and the medical intake records, with usage characterized in terms of occurrence prior to and/or during pregnancy. Illicit drug users during pregnancy had lower self esteem, greater stress, more pregnancy symptoms, a more negative pre-pregnancy body image and less favorable interactions with their partners. T test results show that infants of smokers had smaller head circumferences, shorter body length, and less optimal Brazelton orientation performance. Infants of illicit drug users had smaller head circumferences and shorter body lengths. PMID- 8201450 TI - Nutrition, genital tract infection, hematologic values, and premature rupture of membranes among African American Women. AB - Using a prospective comparative design, African American gravidae with and without genital tract infection were assessed with respect to dietary intakes, serum nutrient values, hematologic values, and pregnancy outcomes. Intakes of ascorbic acid, vitamin A, protein, and iron were the dietary variables while levels of ascorbic acid, protein, albumin, globulin, and ferritin were the variables measured in serum. The hematologic variables included hemoglobin, hematocrit, and red and white blood cell counts. Pregnancy outcome was defined on the basis of premature rupture of the membranes (PROM), and infant birth weight, birth length, gestational age, and head circumference. The sample consisted of 335 nulliparous women who were between 16-35 years of age, 96 of whom had genital tract infection based on laboratory reports. Findings indicated no significant differences between the mean dietary intakes as well as serum values of the infected and non-infected women, and no difference in the incidence of PROM. However, non-infected women had a better mean hematologic profile than the infected gravidae during pregnancy. Also, for the non-infected group, there were significant relationships between head circumference and protein consumption (P = .015) and serum ferritin (P = .05). For the infected women, the relationship between the hemoglobin and hematocrit measurements obtained at the first prenatal visit and infant birth weight, birth length and head circumference were statistically significant. PMID- 8201452 TI - Nipple feeding premature infants in the neonatal intensive-care unit: factors and decisions. AB - OBJECTIVE: To rank factors considered important by neonatal intensive-care unit (NICU) nurses in identifying hunger in infants weighing 1,800 g or less, to rank factors considered important in making decisions about nipple feeding such infants, to determine whether the two rankings varied among hospitals, and to identify the caregiver with the greatest influence over feeding decisions. DESIGN: Descriptive comparative survey. SETTING: NICUs of three metropolitan hospitals. PARTICIPANTS: Forty-seven NICU nurses in those hospitals. MAIN OUTCOME MEASURES: Nurses ranked factors indicating hunger in preterm infants and factors contributing to feeding decisions for such infants. RESULTS: Vigorous sucking, rooting, and crying were ranked as hunger cues. Nonnutritive sucking and a gestational age of 34 weeks or more were considered indicators of readiness to begin nipple feeding. The centrality of the nurse's role in feeding decisions was confirmed. CONCLUSIONS: Additional research is needed to determine whether nonnutritive sucking predicts nutritive sucking performance and to study the nurses' responses to infants who suck poorly or refuse to nipple feed. PMID- 8201453 TI - Women and the family of the future. AB - The complexities of current societal trends impose a daunting challenge to providers of maternal child health services. Demographers, anthropologists, sociologists, policy makers, and health care providers struggle to grasp the multiple issues in an effort to create useful strategies for the 21st century. The 1990s have been labeled the decade of women's health. Legislative and policy efforts have focused new and much-needed attention on women as recipients and providers of health care. The realities of mothers in the work force, the epidemic of adolescent pregnancy, the swelling ranks of women and children in poverty, the increasing number of women with acquired immune deficiency syndrome, the new advances in reproductive technology, and the effect of population and immigration trends greatly influence the childbearing client of the future and create enormous pressures for critical problem solving. PMID- 8201454 TI - Perinatal health care policy: how it will affect the family in the 21st century. AB - Demographic trends, pressures to reduce medical care costs and to improve access, biomedical research, and women's preferences for health care will result in many important changes in perinatal health care during the next 2 decades. These changes have the potential for influencing family structure and functioning. For example, the rates of teen-age pregnancy, unwanted or mistimed pregnancy, and infertility, with all their attendant adverse consequences, might be reduced. PMID- 8201455 TI - Health care reform as an ongoing process. AB - Reform in maternal and infant health care is presented as an ongoing process. Three phases of reform occurring during the past 4 decades that have been initiated or involved nurses are discussed: the childbirth education movement, which signalled the beginning efforts of parents to regain responsibility and control of their birth experience; the acceptance of nurse-midwives as primary care providers working in concert with obstetrical specialists; and the free standing birth center as a holistic environment for the practice of midwifery and the care of women anticipating a medically uncomplicated childbirth experience. These reforms represent a paradigm shift that fits all current proposals for reform of the health care system. PMID- 8201456 TI - The 1990s: a decade for change in women's health care policy. AB - As the 1990s usher in the era of reform, nurses and advocates for women's health must work together to elevate and integrate the concept of caring throughout the new health care system. Nurses must develop strategies to empower and educate women and communities to take charge of their health. To accomplish this, nurses must recognize the impact of health care policy on their profession and practice and activate their political power to make needed changes. PMID- 8201457 TI - Childbearing, reproductive control, aging women, and health care: the projected ethical debates. AB - Of the many social trends that will have an impact on the ethical debates surrounding women's health in the 21st century, three are discussed: the shifting demographics of age and race in the United States; the fundamental change in the health care system to a community-based, preventive model; and the equal voice of women in the government. Using these trends as a framework, this article hypothesizes the ethical debates that will occur in the 21st century concerning such issues as fetal viability, abortion, contraception, infertility, genetic engineering, aggressive versus nonaggressive treatment of aging women, scarce resources, menopause, organ transplants, sexism in biomedical research, fertility in postmenopausal women, birthing centers, fetal surgery, and fetal therapy. PMID- 8201458 TI - Professional nursing education in the future: changes and challenges. AB - Trends in health care suggest changes in nursing practice and implications for nursing education. Changing demographics, emphasis on health promotion, health care costs, movement toward community-based care, and expanding technology are factors that shape the health care system of the future and educational preparation of nurses. This article examines these trends and implications for nursing education. Faculty are faced with preparing students for future practice that will be more complex and specialized than it now is; will be provided in multiple settings; and will require extensive knowledge, critical thinking and other cognitive skills, technologic and psychomotor skills, and a value system for making ethical decisions. Other outcomes of nursing education program include learning to learn, handling ambiguity, thinking like a professional, and accepting responsibility for decisions made in practice. For nursing to assume a central role in the health care system of tomorrow, reform in nursing education is needed today. PMID- 8201459 TI - Genetic-based and assisted reproductive technology of the 21st century. AB - The scientific advances of human genetics and assisted reproductive technology are redefining the concepts of health and illness by revealing the mysteries of the human genome and the process of conception, implantation, and diagnostic testing of the human embryo. The effect of these discoveries and their clinical applications will move from the tertiary to primary care arena through the ability to readily screen, diagnose, and treat some disorders and offer cure as the end result for others. In addition, the ethical, legal, and social issues, along with the attendant implications for professional practice, will need to be identified. Only a small portion of nurses have had to address the knowledge and practice issues associated with these advances. "Brave new families" are being created. Perinatal nurses must be prepared to meet the emerging needs of these families through the art and science of nursing. PMID- 8201460 TI - Fetal surgery: changing the outcome before birth. AB - Today, as we approach the 21st century, research is being conducted in fetal surgery. Given the selection process and the limitations of our present technology, only a few malformations can be managed through a fetal surgical intervention. As the "fetal specialists" develop new techniques and educate others, nurses must remain a critical member of the fetal surgical team. PMID- 8201461 TI - Intrapartal nursing care: research into practice. AB - One of the nursing profession's major goals is to advance the ideal of research based nursing practice. Much has been written during the past decade about the difficulties inherent in achieving the goal of applying research findings to practice. With the increasing national interest in promoting optimal women's health care reforms, one area that should receive renewed interest is that of intrapartal nursing care in the hospital setting. In particular, second stage labor management is supported by considerable research, much of it conducted by nurses, that has not been incorporated into mainstream nursing care. This article discusses the issues surrounding research utilization within the context of nursing practice today, particularly in relation to existing barriers. Using intrapartal nursing care as a focal point to examine these issues, implications for a stronger emphasis on an empirical basis for practice are be identified. Recommendations for approaches to facilitate the process of research utilization by maternity nurse clinicians also is delineated. PMID- 8201462 TI - Sketching the future: trends influencing nursing informatics. AB - Technologies emerging in the fields of telecommunications, video and digital imaging, and microprocessing are shaping the future of nursing practice. To measure up to the future needs of nursing, nurses of today must have the vision and desire to become computer aware and technologically literate. Hypothetical future situations pose challenges related to current nursing informatics and artificial intelligence issues. Discussion includes technology issues related to the lifetime clinical health record. Areas that the Center for Nursing Research considers priorities for informatics suggest directions for nursing technology efforts. This article calls on all nurses to become active in designing and molding future clinical practice systems. PMID- 8201463 TI - Back to the future of women's health and perinatal nursing in the 21st century. AB - Trends in women's health and perinatal nursing practice in the 21st century can be projected through looking back at our profession's history. Highlighted in this preview of nursing's future are the societal influences predicted to promote the essence of professional practice, influence our educational processes, and guide our research investigations. Most important among these influences is that of ritual-busting nursing research, which is predicted to elucidate outcomes of practice and provide the groundwork for change. However, research-driven change endorses the shedding of an antiquated maternity nurse image and practice. A call is made for accountability, ethical thinking, and reciprocal nurse trust for professional survival in the future. PMID- 8201464 TI - Self-administered versus nurse-administered epidural analgesia after cesarean section. AB - OBJECTIVE: To compare two methods of administering analgesia by the epidural route after cesarean sections. DESIGN: Quasi-experimental. SETTING: The postpartum area of a large community hospital. PARTICIPANTS: Fifty women undergoing planned cesarean sections with epidural anesthesia. INTERVENTIONS: The control group received continuous epidural analgesia with nurse-administered boluses and the experimental group with self-administered boluses. MAIN OUTCOME MEASURES: Pain control, side effects from medication, amount of medication required, postoperative activity levels, and patient satisfaction. RESULTS: Subjects receiving continuous epidural analgesia with self-administered boluses of analgesic used significantly less fentanyl and fewer supplemental intravenous pain medications than subjects receiving continuous epidural analgesia with nurse administered boluses of analgesic. CONCLUSIONS: Subjects in self-administered group required less pain medication than subjects in nurse-administered group. PMID- 8201465 TI - Invasive bacterial infections in children born to women infected with human immunodeficiency virus type 1. AB - To determine the rates and characteristics of invasive bacterial infections in children infected with the human immunodeficiency virus type 1 (HIV-1), we conducted a prospective, longitudinal, observational cohort study of infants born to HIV-1-infected mothers between Dec. 1, 1985, and Sept. 30, 1989. Of 104 subjects whose HIV-1 infection status could be definitively determined, 21 were infected with HIV-1 and 83 were not. In all, 11 (48%) of 23 invasive infections occurred among 10 HIV-1-infected patients and 12 (52%) of 23 occurred among 11 uninfected subjects. Infections with Streptococcus pneumoniae (n = 8), all of which were community acquired, accounted for the greatest proportion (35%) of the organisms isolated from either the blood or the cerebrospinal fluid. Five episodes of pneumococcal bacteremia occurred in the HIV-infected patients; all resolved promptly after treatment was begun, and no serious focal infections developed. Of 13 instances of bacteremia with an organism other than S. pneumoniae, seven were nosocomial. The rate of community-acquired invasive bacterial infections among the HIV-infected children was nearly three times higher than the rate in the non-HIV-infected children (overall, 1.02 infections per 100 person-months vs 0.37 infection per 100 person-months; rate ratio, 2.8; p = 0.05). Most of the increased risk occurred in children > 1 year of age. In contrast, the difference in the rates of infection between those patients in the two groups who were less than 12 months of age was not significant (1.3 infections per 100 person-months vs 0.81 infection per 100 person-months; rate ratio, 1.6; p = 0.47). We conclude that the rate of invasive bacterial infection is higher in HIV-infected children than in their peers, especially after 1 year of age. PMID- 8201466 TI - Invasive pneumococcal disease among infected and uninfected children of mothers with human immunodeficiency virus infection. AB - OBJECTIVE: To describe the incidence and clinical presentation of invasive pneumococcal disease in a cohort of children infected with human immunodeficiency virus (HIV) who were prospectively followed from birth, in comparison with uninfected children born to HIV-infected mothers and control children. DESIGN: Prospective follow-up of a cohort recruited at birth and born to mothers with known HIV status. The person-years analysis method used the occurrence of invasive pneumococcal disease as the end point. SETTING: Hospital-based clinic specializing in care of HIV-at-risk and HIV-infected children in Baltimore, Md. PARTICIPANTS: Forty-one vertically HIV-infected children, 128 uninfected children born to HIV-infected mothers, and 71 control children born to mothers with negative findings for HIV but with HIV risk factors. RESULTS: Among HIV-infected children, 10 episodes of invasive pneumococcal disease occurred during the first 36 months of life compared with 4 episodes among uninfected children and 1 episode among control subjects. The relative risk for HIV-infected children versus the combined uninfected and control groups was 12.6 with a 95% confidence interval (5.4, 28.8) and a p value for difference between groups of < 0.001. The incidence rate per 100 child-years of observation during the first 36 months of life was 11.3 for HIV-infected, 1.1 for uninfected, and 0.5 for control children. Clinical and laboratory variables were not useful in identifying HIV-infected children at risk for pneumococcal disease. CONCLUSION: Practical strategies to prevent pneumococcal disease among HIV-infected children need to be developed. PMID- 8201467 TI - Fatal pneumococcal septicemia in hemoglobin SC disease. AB - We retrospectively examined the medical and autopsy records of seven previously unpublished cases of fatal pneumococcal septicemia in children with hemoglobin SC disease. The earliest death occurred in a 1-year-old child who had congenital heart disease with cyanosis; the other children were aged 3 1/2 to 15 years. Only one child had received pneumococcal vaccine or prophylactic penicillin therapy. All seven children had an acute febrile illness and rapid clinical deterioration despite parenterally administered antibiotic therapy and intensive medical support. Erythrocyte pit counts in two patients were 40.3% and 41.7%, respectively (normal, < or = 3.6%). Autopsy data from five cases showed marked splenic congestion without infarction in five, splenomegaly in four, and bilateral adrenal hemorrhage in three. These cases illustrate that functional asplenia predisposes some children with hemoglobin SC disease to the development of fatal septicemia after the age of 3 years. We conclude that pneumococcal vaccine should be administered to all children with hemoglobin SC disease and that acute febrile illnesses should be investigated promptly for the possibility of septicemia. The routine use of prophylactic penicillin therapy in infants and children with hemoglobin SC disease remains controversial. PMID- 8201468 TI - Association of Lewis blood group phenotypes with urinary tract infection in children. AB - Many blood group antigens, genetically controlled carbohydrate molecules, are found on the surface of uroepithelial cells and may affect bacterial adherence and increase the frequency of urinary tract infection (UTI) in adults. Sixty-two children aged 2 weeks to 17 years (mean, 2.3 years) who were hospitalized with fever in association with UTIs caused by Escherichia coli had complete (n = 50) or partial (n = 12) erythrocyte antigen typing to determine the role of erythrocyte antigens and phenotypes in UTI in children; 62 healthy children undergoing nonurologic elective surgery, matched 1 to 1 for age, sex, and race to the patient group, formed the control group. In univariate tests, patients and control subjects did not differ in ABO, Rh, P, Kell, Duffy, MNSs, and Kidd systems by the McNemar test of symmetry (p > 0.05). The frequency of the Lewis (Le) (a-b-) phenotype was higher (16/50 vs 5/50; p = 0.0076) and the frequency of the Le(a + b +) phenotype was lower (8/50 vs 16/50; p = 0.0455) in the patient population than in the control subjects. A stepwise logistic regression model to predict UTI with the explanatory variables A, B, O, M, N, S, s, Pl, Lea, and Leb showed that only the Lea and Leb antigens entered the model with p < 0.1. The Le(a-b-) phenotype was associated with UTI in this pediatric population. The relative risk of UTI in children with the Le(a-b-) phenotype was 3.2 (95% confidence interval, 1.3 to 7.9). Specific blood group phenotypes in pediatric populations may provide a means to identify children at risk of having UTI. PMID- 8201469 TI - Childhood vaccination against chickenpox: an analysis of benefits and costs. AB - OBJECTIVE: To estimate the economic costs and benefits of routine childhood vaccination against varicella infection. DESIGN: Decision-analytic model of the incidence and costs of chickenpox in children assumed to receive varicella vaccine at age 15 months in conjunction with the measles-mumps-rubella vaccine, or not to be vaccinated against varicella. PATIENTS: Hypothetical cohort of 100,000 children. MAIN OUTCOME MEASURES: Costs of vaccination, cumulative incidence of chickenpox to age 25 years, and related disease costs, including medical treatment and work loss. RESULTS: Vaccination of 100,000 children against varicella at age 15 months would cost $4,812,000. The expected number of cases of chickenpox to age 25 years would be reduced from 95,400 to 4800; costs of medical treatment and work loss would correspondingly decline by $1,678,000 and $9,781,000, respectively. On balance, vaccination is estimated to yield net economic benefits of $6,647,000, or $66.47 per vaccinee. CONCLUSION: Vaccination against varicella infection is cost-effective and should be part of the routine immunization schedule for U.S. children. PMID- 8201470 TI - Extracorporeal life support for severe pediatric respiratory failure: an updated experience 1991-1993. AB - OBJECTIVE: The purpose of this study was to examine our recent experience with children who had acute respiratory failure managed with extracorporeal life support (ECLS) from 1991 to 1993, to determine whether a change in survival rate had occurred in comparison with our previous experience. DESIGN: Historic and prospective cohort study. SETTING: A tertiary pediatric referral center. PATIENTS: All non-neonatal pediatric patients treated with ECLS for severe, life threatening respiratory failure were examined. Overall, 25 patients have been managed with this life-support technique in the past 28 months. Eighty-four percent (21/25) were transferred to our medical center because of failure of conventional mechanical ventilation therapy. Descriptive data of the recent cohort were as follows (mean +/- SD): age 60 +/- 75 months, weight 23.6 +/- 24.8 kg, and male gender 44%. Duration of intubation before ECLS was 5.8 +/- 2.7 days. Arterial blood gas values and ventilator settings immediately before ECLS were as follows: fraction of inspired oxygen, 0.98 +/- 0.08; mean airway pressure, 21.6 +/- 6.2 cm H2O; peak inspiratory pressure, 45.5 +/- 9.6 cm H2O; positive end expiratory pressure, 11.0 +/- 4.3 cm H2O; partial pressure of oxygen (arterial), 56 +/- 20 mm Hg (7.4 +/- 2.7 kilopascals); partial pressure of carbon dioxide (arterial), 46 +/- 17 mm Hg (6.1 +/- 2.3 kPa); and estimated alveolar-arterial oxygen tension difference, 572 +/- 81 mm Hg (76.3 +/- 10.8 kPa). Mean duration of ECLS was 373 +/- 259 hours. Of 25 recently treated patients, 22 (88%) survived their life-threatening respiratory illness to be discharged home; this represented a statistically improved survival rate in comparison with the 58% survival rate previously reported by us for similar patients (p < 0.05). Comparisons of arterial blood gas and mechanical ventilation-related variables measured 24 hours before and again immediately before bypass were similar in the two cohorts with the exception of higher mean partial pressure of carbon dioxide (arterial) 24 hours before bypass in the recent treatment group. For our entire experience, younger age groups had greater survival rates; 100% of infants less than 1 year of age survived. CONCLUSIONS: Treatment with ECLS is an evolving pulmonary rescue therapy with an 88% survival rate in our recent experience. The survival rate has improved to levels that may not greatly improve in the near future, especially for patients less than 1 year of age. Better patient selection or improved management strategies or both may be responsible for the improved patient outcome. PMID- 8201471 TI - Acute effects of inhaled nitric oxide in children with severe hypoxemic respiratory failure. AB - To determine the physiologic effects of inhaled nitric oxide (NO) on oxygenation and hemodynamics in children with severe hypoxemic respiratory failure, we studied the acute response to inhaled NO during mechanical ventilation in 17 pediatric patients. Diagnoses included adult respiratory distress syndrome (ARDS) (10 patients), bronchopulmonary dysplasia with viral pneumonitis (6 patients), and acute pneumonitis, caused by respiratory syncytial virus, without chronic lung disease (1 patient). Gas exchange and hemodynamic measurements were compared before and during exposure to inhaled NO (20 ppm) without changing ventilator settings for 30 minutes. Hemodynamic variables, including pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac index, were measured in 10 patients with ARDS. Inhaled NO acutely improved oxygenation in 15 of 17 patients; mean arterial oxygen tension increased from 58 +/- 13 mm Hg (baseline) to 86 +/- 25 mm Hg after 30 minutes (p < 0.01). Inhaled NO lowered mean pulmonary artery pressure (42 +/- 6 mm Hg at baseline to 31 +/- 6 mm Hg; p < 0.01) and intrapulmonary shunt (39% +/- 7% vs 32% +/- 7%; p < 0.01) without changing systemic arterial pressure or pulmonary capillary wedge pressure. Cardiac index increased by 14% (p < 0.01). Fifteen patients were subsequently treated with low dose inhaled NO (3 to 10 ppm) for 1 to 24 days; 5 (50%) of 10 patients with ARDS and 7 (100%) of the 7 non-ARDS patients survived. We conclude that inhaled NO acutely improves oxygenation and lowers pulmonary vascular resistance without causing adverse hemodynamic effects in severe hypoxemic respiratory failure in pediatric patients. Inhaled NO may be a useful adjuvant therapy in children with acute hypoxemic respiratory failure, including infants with bronchopulmonary dysplasia, but whether prolonged low-dose inhalational NO therapy can reduce morbidity or improve survival rates remains unknown. PMID- 8201472 TI - Sexual maturation and obesity in 9- and 10-year-old black and white girls: the National Heart, Lung, and Blood Institute Growth and Health Study. AB - OBJECTIVE: To assess the relationship between pubertal maturation and obesity in 9- and 10-year-old black and white girls. METHOD: Cross-sectional analysis of cohort baseline data. SUBJECTS: A cohort of 2379 girls recruited from selected schools in Richmond, Calif., and greater Cincinnati, Ohio, and from the membership rolls of a prepaid group practice in greater Washington, D.C. RESULTS: Sixty-four percent of black girls had begun pubertal maturation compared with 33% of white girls. In prepubertal girls, racial differences in height, weight, body mass index (kilograms per square meter) and skin-fold thickness were not significant. Within each race, onset of pubertal maturation was associated with greater height, weight, body mass index, and skin-fold measurements. Within 9 year-old girls who had begun pubertal maturation but not reached menarche, black girls were taller and heavier than white girls. Among pubertal but premenarcheal 10-year-old subjects, black girls were taller and heavier and had greater body mass index and subscapular skin-fold values. After analyses were adjusted for pubertal maturation stage by means of pubic hair development, 10-year-old pubertal black girls remained taller and heavier, but racial differences in body mass index and the sum of skin-fold measurements ceased to be significant. CONCLUSIONS: These findings suggest that the initiation of racial differences in obesity are related, at least temporally, to pubertal maturation. PMID- 8201473 TI - Delayed somatic growth and pubertal development in human immunodeficiency virus infected hemophiliac boys: Hemophilia Growth and Development Study. AB - As part of the Hemophilia Growth and Development Study, we investigated the impact of human immunodeficiency virus (HIV) infection on statural growth, weight gain, and skeletal and sexual maturity in more than 300 boys with moderate to severe hemophilia, of whom 62% were infected with HIV. Age-adjusted height and weight were reduced in the HIV-infected subjects (p < 0.001). However, mean weight for height and triceps skin-fold thickness of the infected-boys closely resembled those of the uninfected group. In HIV-infected boys, height for age was positively related to the CD4+ lymphocyte count when the count was < 200 cells/mm3. Age-adjusted serum testosterone levels did not differ by HIV status, but in the infected participants the mean age-adjusted bone age was significantly reduced (p = 0.038) and the distribution of Tanner stages, adjusted for age, differed significantly (p = 0.003). The probability of advancing one or more Tanner stages in the first study year was significantly slowed in HIV-infected boys more than 14 years of age (p = 0.0003). We conclude that linear growth was significantly impaired in boys with hemophilia and HIV infection, but the wasting of malnutrition was not found. The delays in bone age and pubertal maturation strongly suggest that part of the growth failure seen in acquired immunodeficiency syndrome can be attributed to pubertal delay. We speculate that the lack of demonstrable difference in age-adjusted testosterone concentrations might reflect subtle differences in the pattern of secretion of testosterone or in the concentration of sex-hormone binding globulin. PMID- 8201474 TI - Motor and cognitive development in children with congenital hypothyroidism: a long-term evaluation of the effects of neonatal treatment. AB - Although neonatal thyroid screening programs have been of value in preventing cerebral damage, it is still controversial whether patients with congenital hypothyroidism achieve normal motor and cognitive skills. We studied the motor and cognitive skills of 72 children with early-treated congenital hypothyroidism and 35 control subjects at the ages of 7 1/2 and 9 1/2 years. The relative influence of cause, blood thyroxine concentration at the time of screening, and age at the start of thyroxine replacement therapy on motor and cognitive development was investigated. Despite having received treatment at a mean age of 23 days, children with low neonatal thyroxine concentrations (< 50 nmol/L) at screening, particularly children with thyroid agenesis, had significant motor problems and borderline intelligence scores as late as 9 1/2 years of age. Balance and gross motor functions seemed to decline between 7 1/2 and 9 1/2 years of age, whereas language and memory functions seemed to be maintained. Significant correlations between the start of therapy and both motor scores and performance IQ scores at the age of 7 1/2 years in children with severe hypothyroidism show the importance of early treatment for these patients. PMID- 8201475 TI - Vitamin D metabolism and bone mineralization in children with juvenile rheumatoid arthritis. AB - OBJECTIVE: To examine bone mineralization and bone mineral content in a cross sectional population of children with juvenile rheumatoid arthritis (JRA). METHODS: Bone mineral content was measured by single-photon absorptiometry in 44 children with JRA and 37 control children. Serum concentrations of minerals, vitamin D, parathyroid hormone, osteocalcin, bone alkaline phosphatase, and tartrate-resistant acid phosphatase, and urinary concentrations of minerals, were determined. RESULTS: Bone mineral content was decreased in children with JRA. Significantly lower concentrations of osteocalcin (7.4 +/- 3.4 vs 12.5 +/- 2.5 micrograms/L) and bone alkaline phosphatase (78.8 +/- 36.4 vs 123.0 +/- 46.0 IU/L) suggested reduced bone formation; lower levels of tartrate-resistant acid phosphatase (10.3 +/- 4.1 vs 14.4 +/- 5.8 IU/L) and a lower urinary calcium/creatinine ratio (0.07 +/- 0.06 vs 0.12 +/- 0.09) suggested decreased bone resorption. The serum calcium concentration was significantly lower (9.3 +/- 1.0 vs 10.0 +/- 0.4 mg/dl), as was the parathyroid hormone concentration (19.8 +/ 8.6 vs 26.7 +/- 9.3 ng/L); 1,25-dihydroxyvitamin D values (30.1 +/- 10.5 vs 30.4 +/- 9.3 pg/ml) were normal. CONCLUSION: These data suggest that decreased mineralization in JRA is related to low bone turnover; parathyroid hormone and 1,25-dihydroxyvitamin D levels may be inappropriately normal for the decreased serum calcium concentration in children with JRA. PMID- 8201476 TI - Diagnostic value of anti-neutrophil cytoplasmic and anti-endothelial cell antibodies in early Kawasaki disease. AB - OBJECTIVE: To assess the diagnostic potential of anti-neutrophil cytoplasmic antibodies (ANCA) and anti-endothelial cell antibodies (AECA) to distinguish early Kawasaki disease (KD) from febrile diseases resembling KD. DESIGN: Case control study. SETTING: Tertiary care facility. PATIENTS: Eighteen patients with KD tested within 2 weeks of disease onset and before immune globulin therapy; 20 control children with fever and at least one other KD criterion; 21 children with noninflammatory disorders (patients scheduled for elective surgery, or after trauma). METHODS: We detected ANCA by immunofluorescence and enzyme-linked immunosorbent assay (ELISA), and AECA by a cell-ELISA with fixed human umbilical vein endothelial cells. RESULTS: We found that 7 of 18 patients with KD and 6 of 20 febrile control patients had ANCA (by immunofluorescence or ELISA, p value not significant); 3 of 18 patients with KD and 8 of 20 febrile control patients had AECA (p value not significant). One of three patients with KD who had aneurysms had ANCA; none had AECA. CONCLUSIONS: The ANCA and AECA tests used in this study did not differentiate early KD from other childhood diseases with which it may be confused. PMID- 8201477 TI - Comparative study of a whole-cell pertussis vaccine and a recombinant acellular pertussis vaccine. The Italian Multicenter Group for the Study of Recombinant Acellular Pertussis Vaccine. AB - The safety and immunogenicity of an acellular pertussis vaccine containing the genetically detoxified pertussis toxin PT-9K/129G, filamentous hemagglutinin, and pertactin, together with diphtheria and tetanus toxoids, were compared with those of a whole-cell pertussis component-diphtheria-tetanus vaccine. Four hundred eighty infants were enrolled into this prospective, multicenter, double-blind study. Each infant was randomly given three doses of one of the two vaccines at 2, 4, and 6 months of age. Both local and systemic adverse reactions, reported within 48 hours and 7 days of each injection, were less frequent after the acellular vaccine than after the whole-cell vaccine. The enzyme-linked immunosorbent assay titers to pertussis toxin, filamentous hemagglutinin, and pertactin, as well as the pertussis toxin-neutralizing titer measured by the Chinese hamster ovary cell assay, were significantly higher after the acellular vaccine was given. Both vaccines induced adequate levels of anti-diphtheria and anti-tetanus antibodies. We conclude that the recombinant acellular pertussis vaccine produces fewer reactions than the whole-cell vaccine and provides a high antibody response against the antigens of Bordetella pertussis involved in bacterial adhesion and systemic toxic effects. PMID- 8201478 TI - Rickets: another genetic cause. PMID- 8201479 TI - A possible genetic defect in 25-hydroxylation as a cause of rickets. AB - We examined two siblings who had severe rickets at ages 2 and 7 years, respectively, despite a history of adequate vitamin D intake. The patients' sera had calcium concentrations at the lower limits of normal, low phosphate concentrations, elevated alkaline phosphatase activity, and low levels of 25 hydroxyvitamin D. Treatment with high doses of vitamin D2 resulted in resolution of the biochemical abnormalities and radiographic deformities; pharmacologic doses of vitamin D2 were required to maintain normal concentrations of 25 hydroxyvitamin D in the serum even though vitamin D absorption was normal. These children may have a genetic defect of the 25-hydroxylation step in vitamin D activation. PMID- 8201480 TI - Transmission of varicella-zoster virus from a vaccinee with leukemia, demonstrated by polymerase chain reaction. AB - A 5-year-old white boy in remission from acute lymphoblastic leukemia who was receiving maintenance anticancer chemotherapy had approximately 200 vesicular skin lesions 1 month after receiving live attenuated varicella vaccine. About 2 to 3 weeks later, a mild illness resembling varicella occurred in his susceptible siblings and in three of his classmates. Vaccine-type varicella-zoster virus was demonstrated by polymerase chain reaction in swab specimens from vesicular lesions in his two siblings, in whom antibody to varicella-zoster virus also developed. PMID- 8201481 TI - Reversible cardiomyopathy in an infant with unrecognized congenital adrenal hyperplasia. AB - We describe an infant who had a dilated cardiomyopathy and who was later found to have congenital adrenal hyperplasia. The cardiomyopathy resolved after replacement of glucocorticoid and mineralocorticoid. We believe that glucocorticoid deficiency may have played a direct role in the evolution of this cardiomyopathy. PMID- 8201482 TI - Carnitine palmitoyltransferase II deficiency: a new cause of recurrent pancreatitis. AB - An 18-year-old female patient had a history of recurrent pancreatitis after prolonged periods of exercise coupled with a high-fat diet at the ages of 12 and 15 years. After the onset of recurrent myoglobinuria when she was 16 years old, deficiency of carnitine palmitoyltransferase type II (32% residual activity) was diagnosed on the basis of cultured skin fibroblasts. We conclude that deficiency of carnitine palmitoyltransferase type II may be a cause of pancreatitis and should be considered in the differential diagnosis, even in the absence of overt myoglobinuria. PMID- 8201483 TI - Comparison of methods to categorize undernutrition in children. AB - We compared the results of three methods of categorizing undernutrition in a group of 258 children referred for evaluation of "failure to thrive." There was broad variation between the number of children classified as malnourished (75% to 98%) and the degree of undernutrition, depending on the method used. We recommend that categorization systems be used only to define a child as having a risk of possible adverse effects of undernutrition, not as being malnourished. PMID- 8201484 TI - Evaluation of an office- and hospital-based intervention to increase the use of cloth diapers. AB - To evaluate an office-based educational intervention to promote the use of cloth diapers, we randomly assigned parents of 193 infants either to the intervention group or to a control group. The intervention consisted of physician advice and written material on cloth and disposable diapers at the 2-week office visit. Midway through the study, one of the birth hospitals switched to the exclusive use of cloth diapers. The results indicate that the diapering decisions of parents can be influenced by practices in hospitals and by office-based physician and nurse counseling. PMID- 8201485 TI - Low-dose indomethacin therapy and extension of intraventricular hemorrhage: a multicenter randomized trial. AB - We enrolled 61 neonates of 600 to 1250 gm birth weight with evidence of low-grade intraventricular hemorrhage at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that indomethacin (0.1 mg/kg given intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would prevent extension of intraventricular hemorrhage. Twenty-seven infants were assigned to receive indomethacin; 34 infants received saline placebo. There were no significant differences between the two groups in birth weight, gestational age, sex, Apgar scores, percentage of infants treated with surfactant, or distribution of hemorrhages at the time of the first cranial sonogram (echo-encephalogram). Within the first 5 days, 9 of 27 indomethacin treated and 12 of 34 saline solution-treated infants had extension of their initial intraventricular hemorrhage (p = 1.00). Four indomethacin-treated and three saline solution-treated infants had parenchymal extension of the hemorrhage. Indomethacin was associated with closure of a patent ductus arteriosus by the fifth day of life (p = 0.003). There were no differences in adverse events attributed to indomethacin. We conclude that in very low birth weight infants with low grade intraventricular hemorrhage within the first 6 postnatal hours, prophylactic indomethacin therapy promotes closure of the patent ductus arteriosus and is not associated with adverse events, but does not affect the cascade of events leading to parenchymal involvement of intracranial hemorrhage. PMID- 8201486 TI - Frequency and significance of isolation of Ureaplasma urealyticum and Mycoplasma hominis from cerebrospinal fluid and tracheal aspirate specimens from low birth weight infants. AB - To investigate the pathogenicity of Ureaplasma urealyticum and Mycoplasma hominis in preterm infants, we conducted a study to determine (1) frequency of isolation from cerebrospinal fluid and tracheal aspirate specimens and (2) clinical outcomes and effect of erythromycin treatment in ureaplasma-colonized infants. From the cerebrospinal fluid of 920 infants, U. urealyticum was isolated from 2 (0.2%) and M. hominis from none. From tracheal aspirate specimens from 224 infants, U. urealyticum was recovered from 37 (17%) and M. hominis from 4 (2%). Demographic characteristics and clinical outcomes were compared in very low birth weight infants (< 1500 gm) who were culture-positive or -negative for U. urealyticum. Although infants with positive results were less mature than their cohorts with negative results, there were no substantive differences in clinical outcomes between the two groups. Initiation of erythromycin treatment of infants with positive ureaplasma culture results at a mean age of 16.4 days did not appear to alter the clinical outcome. We conclude that in preterm infants (1) infection of the cerebrospinal fluid by U. urealyticum is infrequent, (2) ureaplasma organisms are frequently present in tracheal aspirate specimens but do not appear to be related to the presence or the subsequent development of respiratory disease, and (3) initiation of erythromycin treatment at 1 to 3 weeks of age does not alter the clinical course. PMID- 8201487 TI - Two-year follow-up of infants treated for neonatal respiratory distress syndrome with bovine surfactant. Survanta Multidose Study Group. AB - In 1988 and 1989, a total of 1228 infants were studied in four double-blind, controlled, multidose clinical trials establishing the safety and efficacy of beractant (Survanta intratracheal suspension, Ross Products Division of Abbott Laboratories), a modified bovine lung extract, in prevention and treatment of neonatal respiratory distress syndrome in premature infants. Data on clinical status were collected for surviving infants at hospital discharge and at 6, 12, and 24 months of adjusted age. Significantly fewer beractant-treated infants required supplemental oxygen at discharge (p = 0.036). At 6 months of adjusted age, beractant-treated infants had more wheezing (p = 0.023) than control infants, a reduced need for supplemental oxygen (p = 0.019), and a lower incidence of cerebral palsy (p = 0.020). At 12 months of adjusted age, beractant treated infants had less wheezing than control infants (p = 0.005), and this finding persisted at 24 months of adjusted age (p = 0.008). No circulating antibodies to the proteins present in beractant were found in serum samples at 6 and 12 months of age. These results suggest that the increased survival rate associated with beractant treatment is followed through 2 years of adjusted age by outcomes equivalent to those of untreated control infants. PMID- 8201488 TI - Acyclovir-resistant neonatal herpes simplex virus infection of the larynx. AB - A 10-day-old infant with stridor was found to have herpes simplex virus type 2 infection of the larynx. The infant's poor clinical response to both acyclovir and foscarnet prompted extensive clinical and virologic evaluations, which revealed acyclovir-resistant herpes simplex virus. PMID- 8201489 TI - Scorpion envenomation and antivenom therapy. AB - The clinical course and outcome of scorpion envenomation in 52 children treated in a pediatric intensive care unit without specific antivenom were retrospectively evaluated and compared with those of scorpion envenomation in the 52 preceding cases treated with specific scorpion antivenom. The demographic, clinical, and laboratory features on hospital arrival were similar in the two groups. The lengths of stay in the pediatric intensive care unit and in the pediatric wards were comparable. Hypotension with pulmonary edema developed in four of the children who did not receive antivenom and in one child who did receive antivenom as a complication of the envenomation; all completely recovered. Cardiogenic shock occurred in one child who did not receive antivenom, but who recovered completely, and in three children who received antivenom, of whom two died and one survived with a major deficit. Our study did not demonstrate any beneficial effect of therapy with antivenom for scorpion envenomation in children. However, our "control" group (i.e., the treated group) was a historical one; thus a prospective, randomized study appears to be warranted. Such a study may define specific subgroups that may benefit from treatment with antivenom. PMID- 8201490 TI - Benefit/risk ratio of the antihistamines (H1-receptor antagonists) terfenadine and chlorpheniramine in children. AB - There are few objective studies of the benefit/risk ratio of H1-receptor antagonists in children. We hypothesized that terfenadine would provide as effective peripheral H1 blockade as chlorpheniramine in young patients, but would cause less central nervous system dysfunction. We tested this hypothesis with epicutaneous histamine tests to monitor peripheral H1 blockade, P300-event related potentials as a measure of cognitive processing, and a visual analog scale for somnolence, in a double-blind, single-dose, placebo-controlled, three way crossover study in 15 children with allergic rhinitis (mean age, 8.5 +/- 1.4 years). On 3 different days the children received terfenadine, 60 mg, chlorpheniramine, 4 mg, or placebo; the tests were performed before and 2 to 2 1/2 hours after dosing. Both terfenadine and chlorpheniramine suppressed the histamine-induced wheal and flare compared with baseline and with placebo; terfenadine was significantly more effective (p < 0.05). Terfenadine did not increase the latency of P300-event-related potentials at the parietal (Pz) or frontal (Fz) scalp electrodes compared with baseline, in contrast to chlorpheniramine and placebo, which did increase P300 latency. Terfenadine and placebo did not increase somnolence compared with baseline, but chlorpheniramine did. In children, as previously documented in adults, terfenadine has a more favorable benefit/risk ratio than chlorpheniramine, as shown by production of significantly greater peripheral histamine blockade and significantly less central nervous system dysfunction. PMID- 8201491 TI - Coexistence of glucocorticoid receptor and pharmacokinetic abnormalities: factors that contribute to a poor response to treatment with glucocorticoids in children with asthma. AB - Rapid glucocorticoid clearance and abnormal glucocorticoid receptor binding have been described as factors that contribute to an inadequate response to treatment with glucocorticoids in patients with asthma. We report the coexistence of these abnormalities in children with severe asthma who respond poorly to systemic glucocorticoid therapy. PMID- 8201492 TI - Antineutrophil cytoplasmic autoantibody-positive crescentic glomerulonephritis as a complication of treatment with propylthiouracil in children. AB - Propylthiouracil, which is commonly used in the treatment of hyperthyroidism, has been associated in adults with antineutrophil cytoplasmic autoantibody, a serologic marker of vasculitis. Severe renal disease has not been reported as a complication of therapy with this drug. We report severe antineutrophil cytoplasmic autoantibody-positive vasculitis in children receiving propylthiouracil, as well as rapidly progressive crescentic glomerulonephritis after administration of this drug. PMID- 8201493 TI - Selection of children with precocious puberty for treatment with gonadotropin releasing hormone analogs. PMID- 8201494 TI - Ovarian microcysts with premature thelarche. PMID- 8201495 TI - Incidence of celiac disease. PMID- 8201496 TI - IgA antibodies to gliadin, reticulin, and endomysium for celiac disease screening in children with insulin-dependent diabetes mellitus. PMID- 8201497 TI - Elevated serum aminotransferase activity: an early manifestation of gluten sensitive enteropathy in children with insulin-dependent diabetes mellitus. PMID- 8201498 TI - No resuscitation and withdrawal of therapy in neonatal and pediatric intensive care units. PMID- 8201499 TI - Linoleic acid enhances mitogen response and survival of septic weanling rats. AB - Immunologic responses to various dietary fats and concentrations remain controversial. The authors examined the effect of dietary omega-3 and omega-6 polyunsaturated fatty acids (PUFA) on the immune system of weanling rats. Male weanling Sprague-Dawley rats were fed special liquid diets based on a standard enteral formula: (I) control: 2.2% calories as safflower oil (linoleic acid), (II) omega-3: 2.2% calories as safflower oil and 30% calories as cod liver oil (linolenic acid), and (III) omega-6: 32.2% calories as safflower oil. Body weight and caloric intake were measured daily. Rats were fed special diets for 18 days, at which time they were subjected to either septic challenge with 2 x 10(3) colony forming units of Streptococcus pneumoniae (eight rats per diet group) or killed and a splenocyte mitogen assay performed (four rats per diet group). Supplementation with omega-6 resulted in prolonged survival after bacterial challenge (control, 30.5 +/- 0.5 hours; omega-3, 31.6 +/- 0.5; not significant; omega-6, 39.8 +/- 5.0; P < .05). A significant difference in mitogenic stimulation was seen with omega-3 and omega-6 in response to PHA (control, 10,856 +/- 3,342; omega-3, 14,605 +/- 3,042; P < .05; omega-6, 35,737 +/- 7,596; P < .05) and with omega-6 only in response to LPS (control, 3,543 +/- 1,083; omega-3, 8,777 +/- 1,269; omega-6, 10,101 +/- 3,008). Previous studies have suggested that diets high in omega-6 PUFA are immunosuppressive because of an increase in the production of the dienoic prostaglandins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201501 TI - Overcoming a kinked peel-away sheath during central line implantation. AB - In pediatric patients, central line implantation via the subclavian vein can be complicated by the presence of a kink in the peel-away sheath. A technique is described, which has been used on 62 occasions to overcome this problem. Reinserting the catheter through the kinked peel-away sheath in concert with a guidewire that extends 3 to 4 cm beyond the catheter tip can ensure successful placement. PMID- 8201500 TI - Impairment of nutrient uptake in a rabbit model of gastroschisis. AB - Infants with gastroschisis (GS) commonly require total parenteral nutrition and prolonged hospitalization because of intestinal dysfunction resulting from dysmotility and/or malabsorption. To investigate prepartum small intestinal (SI) nutrient absorption in GS, a fetal rabbit model was surgically created on gestational day 24 (term, 31 to 33 days) in 11 time-mated New Zealand White does in each left ovarian-end fetus. Each right ovarian-end fetus served as a control (C) and was manipulated only. All does, 10 of 11 GS fetuses (91%), and 8 of 11 C fetuses (73%) survived to gestational day 30. GS fetuses had significantly reduced total body weights, SI weights, and SI lengths compared with C fetuses. Using the everted mucosal sleeve technique, the uptakes of an amino acid (proline) and a sugar (glucose) were determined. The uptakes of proline per milligram SI, proline per centimeter SI, and glucose per milligram SI were significantly impaired in GS fetuses compared with C fetuses (P < .04 by Student's paired t test). The uptake of glucose per centimeter SI was also reduced in GS fetuses, but not significantly. Uptake capacities (a measure of the entire SI's ability to absorb a given nutrient) were significantly reduced in GS fetuses compared with C fetuses (proline, 2,670 +/- 612 nmol/min/entire SI v 6,842 +/- 399 nmol/min/entire SI, P < .008 by Student's paired t test; glucose, 402 +/- 69 nmol/min/entire SI v 950 +/- 103, P < .008 by Student's paired t test). PMID- 8201502 TI - An inexpensive device for perioperative positioning of pediatric patients. AB - Intraoperative positioning of the pediatric patient during venous access procedures is crucial. Currently such patients are positioned with a sandbag beneath the shoulders and in a head-down position. This has significant limitations because the bag must be removed for subsequent on-table radiography. The authors have devised a simple inexpensive technique that obviates this need and facilitates the procedure. They have used the device in over 80 patients undergoing venous access. No problems relating to the device have been noted, and on-table x-rays are readily facilitated. PMID- 8201503 TI - Transaxillary upper thoracic sympathectomy for primary palmar hyperhidrosis in children and adolescents. AB - Primary palmar hyperhidrosis is part of a triad of palmar, plantar, and axillary hyperhidrosis of unknown etiology, affecting children, adolescents, and young adults. Sixty-seven children and young adolescents were operated on during a 10 year period. A total of 103 transaxillary upper thoracic sympathectomies (36 bilateral) were performed, with no mortality. The immediate postoperative course was uneventful in 90%; the other 10% had mostly minor problems. The average hospitalization period was 3 to 4 days. Total abolition of palmar sweating was achieved in all but two patients in whom some residual moisture remained. Long term extreme satisfaction was reported by 64 of 67 patients (94%). One was moderately satisfied, and two were not satisfied because of excessive "compensatory" sweating elsewhere. Compensatory sweating of some degree was reported by 45% of patients but did not alter satisfaction. By further limiting ganglionectomy to just one ganglion (T2 or T3), compensatory sweating possibly may be reduced further. Early surgery for severe palmar hyperhidrosis will save a child many years of agony and social discomfort because all types of conservative therapy are ineffective and cause unnecessary delay. A limited transaxillary upper thoracic sympathectomy is presently the authors' preferred approach, although ablation via thoracoscopy should not be excluded as further experience is gained with this modality. PMID- 8201504 TI - Palmar hyperhidrosis in children: treatment with video endoscopic laser sympathectomy. AB - Palmar hyperhidrosis (PH) often starts in childhood and can be a disabling condition for a significant number of young children at the age they begin primary school. There are few reports regarding the surgical treatment of PH in children. The authors report on 40 PH patients under 16 years of age treated with video thoracoscopic laser sympathectomy; there has been substantial experience with this procedure for the treatment of adults with PH. A satisfactory result, with very low morbidity, was achieved for all 40 children. The surgical technique is described briefly. With the technique, the proper sympathetic segment is visualized in almost all cases and then definitely ablated with a fiberoptic low power laser while under the aid of sympathetic monitoring. Consequently, an adequate sympathectomy warranting a long-lasting therapeutic effect can be achieved without the need of tissue diagnosis. No case required conversion to open sympathectomy. Neither injury to the lung nor bleeding was encountered. Horner's syndrome did not occur in any case. Bilateral sympathectomy was accomplished generally within 30 minutes. All patients were discharged after an overnight stay and are doing well with normal activities. The most frequent complication was compensatory hyperhidrosis, which was tolerable after reassurance. Based on the accumulated experience, it is justified to recommend early surgery, with this refined technique, in cases of severe PH in children. PMID- 8201505 TI - Surgical treatment of pulmonary hydatidosis in children: experience in 92 patients. AB - Ninety-two patients with a total of 112 pulmonary hydatid cysts underwent surgical treatment in our clinic between January 1980 and January 1992. Nine patients were found to have concomitant liver and pulmonary hydatid cysts. There were 65 boys and 27 girls; the age range was 5 to 14 years. The authors performed cystotomy and capitonnage in 78 patients, lobectomy in 9, segmentectomy in 3, and wedge resection in 2. Of 9 cases with concomitant liver and pulmonary hydatid cysts, 8 were approached by right thoracophrenotomy and 1 by median sternotomy and right phrenotomy. A one-stage operation via median sternotomy was performed in 3 patients who had bilateral pulmonary hydatid cysts. To prevent the development of secondary hydatid cysts because of spillage of hydatid fluid, the authors used 10% povidone-iodine poly (1-vinyl-2-pyrrolidone)-iodine complex intraoperatively as a scolicidal agent. There was no mortality or recurrence in the series. PMID- 8201506 TI - Latissimus-sparing thoracotomy in the pediatric patient: a valuable asset for thoracic reconstruction. AB - The traditional posterolateral thoracotomy involves division of the latissimus dorsi muscle (LD). While the division results in no functional disability, it does negate the potential for possible future thoracic reconstruction if required in individual cases (eg, bronchopleural fistula, empyema, etc). A latissimus sparing thoracotomy (LST) mobilizes the muscle dorsad and does not compromise the operation. Thus, the ipsilateral LD can be used when chest wall reconstruction is required. This option has been used frequently for adults; however, its use in children has not been extensively documented. Microvascular anastomoses for a contralateral LD free-flap may be tenuous in the small vessels of the child; thus, reconstruction using the ipsilateral LD could be beneficial and safer. The feasibility of LST has not been established with regard to the chest of the child. The authors present three pediatric thoracic cases that illustrate the value of this procedure, and discuss different situations in which latissimus sparing thoracotomy is advantageous. PMID- 8201507 TI - Potential danger of 'trial of life' approach to congenital diaphragmatic hernia. AB - This is the report of a newborn girl who was treated by "trial of life" before surgical repair of her left-sided diaphragmatic hernia. Surgery was performed 60 hours after birth, at which time she was found to have an organo-axial volvulus of the stomach. Her postoperative course was complicated by a jejunal perforation on the fourth postoperative day, necessitating another laparotomy. PMID- 8201508 TI - Acute peritoneal dialysis in preterm newborns and small infants: surgical management. AB - Experience with acute peritoneal dialysis gathered over the last 10 years shows that, in 63 premature newborns and infants (up to 1 year of age), a standardized surgical procedure using a silicone catheter with a Dacron cuff (individually glued to fit) has a lower complication rate and is more effective than placement of a trocar catheter. PMID- 8201509 TI - Use of distal splenorenal shunt in children referred for liver transplant evaluation. AB - Variceal bleeding remains a common cause of morbidity for children with both intrahepatic and extrahepatic portal hypertension. Occasionally, patients referred for liver transplant evaluation have significant variceal bleeding, despite adequate synthetic liver function. During a 7-year period, 322 children were referred for liver transplant evaluation. Six underwent distal splenorenal shunt surgery after evaluation. There were four boys and two girls. The average age was 11 +/- 4 years, and the average weight was 39 +/- 15 kg. The etiology of variceal bleeding was intrahepatic portal hypertension in five (1 biliary atresia, 2 chronic hepatitis, 2 congenital hepatic fibrosis) and extrahepatic portal vein thrombosis in one. Two patients had no previous attempts at sclerotherapy (one because of an abnormality in platelet function, the other because of extensive gastric varices), and four had multiple previous sclerotherapy treatments. No patient had preoperative encephalopathy. Three cases were Child's class A, and three were Child's class B. Preoperative evaluation of the portasystemic system was performed with magnetic resonance (MR) imaging or splenoportography. All patients underwent a distal splenorenal shunt procedure, four of whom also had splenopancreatic disconnection. One patient required 100 mL of blood replacement, and five required no blood. The average length of hospital stay was 9.8 +/- 2.2 days. Postoperative complications were minimal. All patients are alive, without recurrent gastrointestinal bleeding or encephalopathy, and they have patent shunts, which was confirmed by MR or Doppler ultrasound at a mean of 25 +/- 20 months after shunt surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201511 TI - Sequential sac ligation for giant omphalocele. AB - The authors describe a technique for the management of giant omphalocele in which the sac is not resected, but used to sequentially reduce the contents into the abdominal cavity. Three patients were treated in this fashion. Delayed primary fascial closure was achieved in two. The third patient did not have complete reduction after 3 weeks, and temporary placement of a silastic sheet was required. The sac remained intact in all three cases, and neither infection nor injury to the abdominal contents occurred. This technique has the advantages of maintaining an intact membrane and avoiding the initial operative placement of a prosthetic silo in these sometimes critically ill neonates. PMID- 8201510 TI - Surfactant (beractant) therapy for infants with congenital diaphragmatic hernia on ECMO: evidence of persistent surfactant deficiency. AB - Infants with congenital diaphragmatic hernia (CDH) on extracorporeal membrane oxygenation (ECMO) can have initial lung atelectasis which, in survivors, gradually improves over time. To test the hypothesis that these patients could benefit from surfactant therapy, infants with CDH (born at > 34 weeks' gestation) on ECMO received either four doses of modified bovine lung surfactant extract (beractant) (surfactant group, n = 9) or an equal volume of air (control group, n = 8). Tracheal aspirate surfactant protein-A (SP-A) concentrations were initially low, and then increased over time in both CDH groups (P = .0021); however, levels remained low when compared with those of infants on ECMO who had other diagnoses (P = .04). Lung compliance (CL), time to extubation, time on oxygen, and total no. of hospital days were not different between the two groups. Infants with CDH had persistently elevated right ventricular pressure (RVP) at cessation of bypass when compared with non-CDH infants on ECMO (RVP = 53.25 mm Hg +/- 19.52 in the CDH group, 32.90 +/- 10.63 in the non-CDH group; P = .0121). The findings suggest that the postnatal surfactant deficiency may be more persistent in CDH infants than in non-CDH infants on ECMO. However, CDH remains a multifactorial condition, with delayed improvement, because of persistence of pulmonary hypertension, difficulties with vascular remodeling, degree of lung hypoplasia, or compromised respiratory mechanics. PMID- 8201512 TI - Use of neomycin as the prophylaxis against recurrent cholangitis after Kasai portoenterostomy. AB - Ascending cholangitis after portoenterostomy for biliary atresia often leads to significant morbidity. The long-term prognosis also involves recurrent and frequently recalcitrant bouts of cholangitis. Attempts at prophylaxis with use of oral antibiotics are frequently unsuccessful. The authors describe three patients who, after successful portoenterostomies, were plagued with recurrent bouts of cholangitis, despite the use of a variety of antibiotics. The authors instituted oral neomycin as prophylaxis and nearly eliminated this serious complication. PMID- 8201513 TI - Effects of ursodeoxycholic acid treatment on essential fatty acid deficiency in patients with biliary atresia. AB - To assess whether ursodeoxycholic acid (UDCA) treatment has any beneficial effect on essential fatty acid (EFA) deficiency in patients who have had a Kasai operation for extrahepatic atresia (EBA), responses of serum fatty acids to UDCA administration (15 mg/kg/d) were investigated in eight jaundice-free patients and in eight patients with jaundice (serum total bilirubin > or = 1.0 mg/dL). All patients were also given taurine supplementation (100 mg/kg/d). Serum fatty acid composition was determined before and 6 months after UDCA treatment. Serum total bile acid concentration and serum total bilirubin value, as a part of conventional liver function tests, were measured before and during UDCA therapy. Before UDCA treatment, the concentrations of linoleic acid and arachidonic acid were significantly lower (P > .05 for the former; P > .01 for the latter) in both the jaundice and jaundice-free groups than in the controls. After 6 months of treatment, the linoleic acid concentration significantly increased (P > .05), to the normal range, in the jaundice-free group, but not in the jaundice group. The arachidonic acid concentration did not increase significantly in either group. The serum total bile acid concentration was lower in six of the eight jaundice free patients and in four of the eight jaundice patients. The serum total bilirubin value decreased in six of the eight jaundice-free patients and in four of the eight jaundice patients; however, the degree of improvement was not statistically significant in either group. No side effects developed, and there were no changes in blood chemistry values unrelated to liver disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201514 TI - Fenestrated duodenal membranes: an analysis of symptoms, signs, diagnosis, and treatment. AB - Duodenal obstruction typically occurs in the ampullary region and presents in the early neonatal period. If the obstruction is incomplete, as with a fenestrated duodenal membrane, the presentation may be delayed and the diagnosis overlooked. Sixteen patients with fenestrated duodenal membranes presented over a 23-year period. Six presented in the neonatal period, with vomiting; an abdominal x-ray was diagnostic in four. Ten presented later (5 weeks to 14 years) with nonspecific symptoms, ie, failure to thrive, postprandial epigastric distension, and recurrent chest infections. Vomiting occurred in all, but was of short duration (< 1 week). Two patients in the delayed group had Down's syndrome. Diagnosis was confirmed on barium meal, and optimal surgical treatment was a bypass duodeno-duodenostomy. The diagnosis of fenestrated duodenal membrane must be considered in all cases with symptoms and signs suggestive of upper gastrointestinal tract obstruction, and excluded by contrast radiology. PMID- 8201515 TI - Fistula-in-ano in infancy and childhood. AB - The authors report the results of a retrospective study of 36 patients with fistula-in-ano (FIA) and/or perianal abscess (PA) presenting during a 3-year period. In 76.2% of the 21 patients with FIA, the fistulae developed in the first 2 years of life. For eight of the 16 patients who underwent fistulectomy, histological examination of the excised fistulae showed an epithelial lining of the tract mixed with stratified squamous, transitional and columnar epithelium. The early onset of FIA, the high percentage of bilateral and multiple fistulae, and the presence of these types of epithelium lining support a congenital etiology of FIA in children. In boys, a causal relationship exists between PA and FIA. PMID- 8201516 TI - The embryology and management of congenital pouch colon associated with anorectal agenesis. AB - Forty-one infants with a pouch colon malformation accompanied by a high anorectal anomaly were treated between January 1986 and December 1990. The 41 cases constituted 9% of all anorectal malformations and 15.2% of high defects managed during this period. There were 32 boys and nine girls; three of the girls had an associated cloaca. Many of the babies presented in poor condition, with gross abdominal distension caused by the distended colonic pouch. The typical radiological feature was an enormously distended colonic shadow occupying more than 50% of the width of the abdomen. At the time of surgery, the patients were classified into 4 subgroups based on the length of the normal colon. All but three infants had a high wide fistula, with the genitourinary tract consisting of a colovesical fistula in males and a colovaginal or colocloacal fistula in females. Frequent associated malformations included duplication of the appendix and vesicoureteric reflux. The operations performed initially were a window colostomy of the pouch with or without division-ligation of the fistula, end colostomy after fistula ligation, or subtotal pouch excision with tubularization of the remaining colon and end-colostomy. Thirteen of the 41 patients have undergone a definitive pull-through operation using the posterior sagittal approach, including two children in whom one-stage reconstruction of a cloaca was performed. Standardized management of this complex anomaly is proposed for the initial operation and for definitive reconstruction. PMID- 8201517 TI - Anal endosonography and physiology in adolescents with corrected low anorectal anomalies. AB - Sixteen patients aged 12 to 16 years (mean, 14.9) with corrected low anorectal anomalies, and eight age-matched controls were studied. Eight patients were totally continent, six had staining, and two had fecal soiling. Half the patients had trouble with constipation. The grade of incontinence was related to significantly reduced resting and squeeze pressure in the anal canal. Girls had significantly worse results than boys. The anal sphincter muscle complex was visualized by anal endosonography, and images of the external anal sphincter corresponded to the results of the surface electromyography. In addition, anal endosonography provided a detailed picture of all perianal structures including the internal anal sphincter. Anal endosonography supplements other imaging techniques for assessing the perianal structures in patients who have an accessible anal canal. PMID- 8201518 TI - Varicocele and the horizontal testis: a change in position? AB - Horizontal lie of the testis has recently been observed in association with varicoceles in a pediatric population. Six children with a varicocele presented to the surgical department during a 6-month period. All had an associated horizontal lie of the testis. In two of these cases, high ligation of internal spermatic veins was performed, after which one reverted to a vertical position with resolution of the varicocele. Seven children who underwent high ligation of a varicocoele over a 5-year period were examined. All were found to have no evidence of the varicocele at follow-up. All but one had a vertical lie. Horizontal lie of the testis in children is a new clinical sign that should alert the examiner to the possibility of an underlying varicocele. PMID- 8201519 TI - Renal agenesis: an acquired condition? AB - Renal agenesis is a relatively common congenital anomaly, although its etiology is unknown. It is clear that some solitary kidneys are the result of postnatal involution of multicystic dysplastic kidneys. The authors present a series of nine neonates with abnormal prenatal renal ultrasound findings; subsequent postnatal investigations showed an absent kidney. Five children had a prenatal diagnosis of multicystic dysplastic kidney (MDK) and two of hydronephrosis. In five cases (56%) there was a contralateral renal unit anomaly. It appears that MDK, and occasionally hydronephrosis, can involute prenatally, producing the postnatal appearance of renal agenesis. PMID- 8201520 TI - Prediction of disease-free survival after therapy in Wilms' tumor using nuclear morphometric techniques. AB - The outlook for children with Wilms' tumor has markedly improved with the use of multimodal therapy, and survival currently exceed 85%. Current trends have been to use less intense therapy for children whose tumors have favorable histology (FH). By decreasing the amount of therapy given to patients whose conditions have an excellent chance of responding, the need for accurate criteria to separate high-risk and low-risk groups becomes imperative. Nuclear morphometric techniques have been developed and extensively tested in the author's laboratory. Preliminary studies of FH Wilms' tumors demonstrated the applicability of this technique. Herein, the authors present a retrospective study of 108 patients with FH tumors, with a mean follow-up period of 1,994 +/- 107 days (66 months) for those whose tumors did respond to therapy, and 686 +/- 61 days (23 months) for those whose tumors did not respond. The univariate predictors were age (P = .02), the skewness of nuclear roundness factor (SNRF) (P = .009), and the mean of the lower five values for nuclear ellipticity, measured by the feret diameter method (L5EFD) (P = .01). A multivariate analysis combining all three variables better separated the two groups (P = .00016). A probability function curve was constructed to predict poor prognosis. Kaplan-Meier actuarial survival analysis was used to predict disease-free survival as clinical progression, and separated the two groups (P = .0004, Wilcoxon-Gehan statistic). These results suggest that nuclear morphometry is useful in the initial assessment of patients with Wilms' tumor. PMID- 8201522 TI - A study of the percutaneous absorption-enhancing effects of cyclodextrin derivatives in rats. AB - 2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and 2,6-dimethyl-beta cyclodextrin (D-beta-CyD) were studied for transdermal penetration enhancement of the cytochrome P450 inhibitor liarozole by an in vivo transdermal absorption rat model. The mode of action of penetration enhancement was investigated by differential scanning calorimetry (DSC). In-vivo, HP-beta-CyD, as a 20% aqueous solution, increased the absorption of liarozole approximately threefold and a 20% aqueous solution of D-beta-CyD decreased the percutaneous absorption of liarozole in blood by a factor of 0.6. However, pretreatment with D-beta-CyD (20%, 4 h) enhanced the transdermal absorption 9.4-fold. In the DSC experiments the thermal profile of human stratum corneum was practically unchanged after treatment with HP-beta-CyD, but treatment with D-beta-CyD revealed an interaction of D-beta-CyD with the protein and lipid fraction. Thus the results from DSC and those from the permeability experiments revealed that D-beta-CyD acts as a transdermal absorption enhancer by changing the stratum corneum barrier whereas HP-beta-CyD influences the partitioning behaviour of the drug in the skin. PMID- 8201521 TI - Primary chemotherapy for children with rhabdomyosarcoma of the 'special pelvic' sites: is preservation of the bladder possible? AB - Twenty-one children with rhabdomyosarcoma involving the "special pelvic" sites, defined as such occurring in the bladder, prostate, vagina and uterus, were treated with primary surgery between 1969 and 1977, and with primary chemotherapy beginning in 1978. Among 11 patients in the latter group who were placed in Clinical Group III (according to the classification of the US Intergroup Rhabdomyosarcoma Study (IRS), six showed partial response (PR) and underwent tumorectomy by radical surgery an average of 6 months after the start of treatment, and three showed complete response (CR) and were treated with further chemotherapy in the hope that cystectomy could be avoided. However, in the latter group, the tumor recurred (39 months, 35 months, and 27 months later), and all eventually underwent total cystectomy. Seven of the nine long-term survivors underwent total cystectomy and have premanent urinary-cutaneous stomas. Two had tumor-free bladders, but function was impaired in one because of the effect of irradiation. Normal function was preserved in only one patient in the series, whose tumor was located at the dome of the bladder. To preserve bladder function in children with rhabdomyosarcoma in these sites, more effective forms of chemotherapy will be required. PMID- 8201523 TI - Use of powdered cellulose for the production of pellets by extrusion/spheronization. AB - The use of powdered cellulose instead of microcrystalline cellulose in the extrusion/spheronization process was investigated. The aim of the study was to assess differences between two types of powdered cellulose using a 2(4-1) fractional factorial design. Water content and amount of binder were found to be most important while type of cellulose and screw speed had only negligible influence on the extrusion process and the resulting pellets. Pellets obtained with powdered celluloses showed higher porosities and faster dissolution rates compared with those made with microcrystalline cellulose. Image analysis was found to be an appropriate method for the simultaneous characterization of pellet size and shape. PMID- 8201524 TI - Incorporation of alpha-tocopherol in liposomes promotes the retention of liposome encapsulated glutathione in the rat lung. AB - The present study was undertaken to investigate whether alpha-tocopherol incorporated in liposomes could improve the retention of entrapped glutathione (GSH) in the lung following intratracheal instillation in rats. Rats were treated with a single dose of [3H]GSH entrapped in liposomes with or without 30 mol% alpha-tocopherol and killed 0, 24 or 48 h later. The retention of GSH in the lung was assessed by measuring the recovery of either 3H-label or GSH in the lung. Animals instilled with free [3H]GSH were found to retain only 2% of the administered dose at 24 h after treatment and no detectable radioactivity at 48 h. Liposome encapsulation altered the pulmonary retention of GSH with 18 and 10% of radioactivity remaining in the lung at 24 and 48 h post-treatment, respectively. The instillation of GSH encapsulated in alpha-tocopherol-containing liposomes resulted in the highest level of GSH retention in the lung, namely 37 and 30% of the administered GSH dose at 24 and 48 h, respectively. Results from Sepharose 4B column chromatography revealed that lung homogenates, obtained from rats instilled with GSH entrapped in alpha-tocopherol-containing liposomes, 24 and 48 h earlier, contained 2 eluted GSH-related components--one associated with the liposomal lipid marker in the void volume and the other as free GSH tripeptide, suggesting a slow sustained release effect mediated by the liposomal formulation. The same liposome preparation containing both alpha-tocopherol and GSH also conferred better protection against FeADP-induced lipid peroxidation than liposomes containing either alpha-tocopherol or GSH alone, indicative of a potentially effective antioxidant formulation for treating oxidative lung injury. PMID- 8201525 TI - The vagus nerve and its non-cholinergic mechanism in the modulation of ethanol induced gastric mucosal damage in rats. AB - The role of the cholinergic pathway in the vagus nerve in modulating gastric lesion formation by ethanol was examined, using an ex-vivo stomach chamber preparation. Subdiaphragmatic vagotomy significantly increased the lesion areas but lowered acid secretion and gastric mucosal blood flow (GMBF). Atropine had no effect, whereas pirenzepine antagonized ethanol-induced mucosal damage. All three procedures showed similar potencies in depressing acid secretion, but only pirenzepine reversed the fall in the GMBF produced by ethanol. These differential effects of vagotomy, atropine and pirenzepine on gastric function suggest that the cholinergic component in the vagus nerve may not be important in the formation of ethanol-induced gastric damage. The persistent protective action as well as the restoration of ethanol-induced GMBF drop by pirenzepine in vagotomized animals further support this hypothesis. The worsening effect of vagotomy is probably modulated by a non-cholinergic mechanism, the abolition of which makes the gastric mucosa more susceptible to damage by ethanol. The acid independent protective action of pirenzepine and its influence on the GMBF, which were not exhibited by atropine, are indeed unique and perhaps may be attributed to this non-cholinergic pathway. PMID- 8201526 TI - Metabolism and transport of the pentapeptide metkephamid by brush-border membrane vesicles of rat intestine. AB - Intestinal metabolism and transport of the pentapeptide metkephamid (Tyr-D-Ala Gly-Phe-N-Me-Met-NH2) were studied using isolated brush-border membranes from the rat. Analysis of the metabolic fragments of enzymatic hydrolysis revealed that cleavage of the N-terminal peptide bond leads to the formation of tyrosine and a tetrapeptide D-Ala-Gly-Phe-N-Me-Met-NH2. The inactivation was due to aminopeptidase N activity and could be inhibited by peptidase inhibitors puromycin, bacitracin and certain dipeptides. Transport studies demonstrated uptake of the intact pentapeptide into the intravesicular space of the vesicles. The transport was a first-order process; no participation of known intestinal peptide carrier systems in the transport of metkephamid could be shown. Modelling of simultaneous metabolism and transport kinetics suggests strategies to improve the fraction absorbed of a peptide by either decreasing its affinity to the metabolizing enzymes (increase Km) or decreasing the concentration of the metabolizing enzymes e.g. by delivering the peptide to an absorption site with reduced enzymatic activity (decrease Vmax) or increasing its absorption velocity. PMID- 8201527 TI - Inhibition of platelet thromboxane formation and phosphoinositides breakdown by diisoeugenol. AB - Diisoeugenol inhibited the platelet aggregation and ATP release of rabbit platelets caused by ADP, arachidonic acid, platelet-activating factor (PAF), collagen and thrombin. Prolongation of the incubation time of platelets with diisoeugenol did not cause further inhibition and the aggregability of platelets could not be restored after washing. In human platelet-rich plasma, diisoeugenol inhibited the biphasic aggregation and ATP release induced by adrenaline and ADP in a concentration-dependent manner. Thromboxane B2 formation caused by arachidonic acid, collagen and thrombin was markedly inhibited by diisoeugenol in a concentration-dependent manner. Diisoeugenol also inhibited the formation of inositol monophosphate caused by collagen, PAF and thrombin. The cAMP level of washed platelets was not changed by diisoeugenol. It is concluded that the antiplatelet effect of diisoeugenol is due to the inhibition of thromboxane formation and phosphoinositides breakdown. PMID- 8201528 TI - Ex-vivo and in-vivo antithrombotic effect of triflavin, an RGD-containing peptide. AB - Triflavin, an Arg-Gly-Asp-containing snake venom peptide, inhibits platelet aggregation through the blockade of fibrinogen binding to the activated platelets. It binds to fibrinogen receptors associated with the glycoprotein IIb/IIIa complex with a Kd value of 7 x 10(-8) M. In this study, we found that 125I-triflavin reached the maximal binding to human platelets within 5 min at 25 degrees C. In addition, when triflavin was intravenously administered at 1.0 mg kg-1 to rabbits, it reversibly impaired the platelet aggregation of platelet-rich plasma caused by ADP (20 microM) ex-vivo over 30 min. The platelet counts of the experimental rabbits remained unchanged. Triflavin was effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice when administered intravenously at a dose of 2 micrograms g-1. Therefore, triflavin was proven to be an effective antithrombotic agent in preventing ADP-induced acute pulmonary thromboembolism in mice and impairing reversibly the platelet function of rabbits when given intravenously. PMID- 8201529 TI - Plasma protein binding of the experimental antitumour agent acridine-4 carboxamide in man, dog, rat and rabbit. AB - The plasma binding of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (AC) was investigated in-vitro by equilibrium dialysis for 3 h at 37 degrees C against isotonic phosphate buffer (pH 7.35) using [3H]AC. There were significant species differences with the smallest % free fraction (mean +/- s.d.) occurring in human plasma (3.4 +/- 0.2), followed by dog (8.1 +/- 0.4), mouse (14.8 +/- 0.8), rat (16.3 +/- 0.9) and rabbit (20.2 +/- 0.7). In plasma from healthy individuals (n = 5), the % free fraction ranged from 2.7 to 3.8. In physiological solutions of human proteins, the greatest binding was observed for alpha 1-acid glycoprotein (AAG) (0.75 g L-1) with a mean free fraction of 24.1 +/- 2.2%, followed by albumin (40 g L-1) with 31.6 +/- 0.7 and 39.8 +/- 2.5% for fatty-acid-free and globulin-free, respectively. There was also some binding to globulins (5 g L-1) with a mean % free fraction of 70.3 +/- 1.6 and 84.8 +/- 2.2 for Cohn's fraction I and IV, respectively. Binding data from the displacement of [3H]AC by increasing concentrations of AC in human AAG (0.75 g L-1) or albumin solution (40 g L-1) indicated that AAG had 10-fold greater binding affinity for AC (Ka, 7.8 x 10(4) M-1) compared with albumin (Ka, 6.8 x 10(3) M-1). In human plasma enriched with AAG there was a significant negative linear correlation (r = 0.932; P < 0.001) between % AC free fraction and increasing AAG concentration over the range 0.6-4.5 g L-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201531 TI - The effect of colestipol and cholestyramine on the systemic clearance of intravenous ibuprofen in rabbits. AB - The effect of oral administration of the non-absorbable anion-exchange resins cholestyramine and colestipol on the systemic clearance and other pharmacokinetic parameters of intravenously administered ibuprofen (25 mg kg-1) was studied in rabbits. Single doses of colestipol hydrochloride (0.4 g kg-1) or cholestyramine (0.17 g kg-1) were given 30 min before ibuprofen administration. In cholestyramine-treated rabbits a significant reduction in ibuprofen plasma concentration was observed compared with both control (water only) and colestipol treated rabbits. Cholestyramine treatment resulted in a significant decrease in the terminal elimination half-life and the mean residence time. Furthermore, a 31% increase in the systemic clearance and 23% decrease in the area under the plasma concentration-time curve were also observed in cholestyramine-treated rabbits. Colestipol treatment did not change these parameters. The volume of distribution parameters (Vdss and Vd(area)) did not change following either treatment. The changes in the pharmacokinetic parameters are compatible with an acceleration of ibuprofen elimination induced by oral administration of cholestyramine and not by colestipol. This effect is thought to be due to augmentation of net biliary excretion through enteric binding. PMID- 8201530 TI - Pharmacokinetics and cardiovascular effects of YM-21095, a novel renin inhibitor, in dogs and monkeys. AB - The pharmacokinetics and cardiovascular effects of YM-21095 ((2RS), (3S)-3-[N alpha-[1,4-dioxo-4-morpholino-2-(1-naphthylmethyl)- butyl]-L-histidylamino]-4 cyclohexyl-1-[(1-methyl-5-tetrazolyl)thi o]-2-butanol), a potent renin inhibitor, have been studied in beagle dogs and squirrel monkeys. Plasma levels of YM-21095 after 3 mg kg-1 intravenous dosing to dogs declined biphasically and fitted a two compartment model. Kinetics were as follows: t1/2 alpha = 4.9 +/- 0.2 min, t1/2 beta = 2.76 +/- 0.79 h, Vdss = 3.86 +/- 1.04 L kg-1, plasma clearance = 2.22 +/- 0.39 L kg-1, and AUC = 1445 +/- 266 ng h mL-1. After 30 mg kg-1 oral dose, maximum plasma concentration, tmax and AUC of YM-21095 were 28.8 +/- 9.6 ng mL-1, 0.25 h and 23.6 +/- 7.7 ng h mL-1, respectively. Systemic bioavailability as determined on the basis of the ratio of AUC after intravenous and oral dose was 0.16 +/- 0.04%. In conscious, sodium-depleted monkeys, YM-21095 at an oral dose of 30 mg kg-1 lowered systolic blood pressure and inhibited plasma renin activity without affecting heart rate and plasma aldosterone concentration. Maximum plasma concentration of YM-21095 after 30 mg kg-1 oral dose to monkeys was 71.8 +/- 41.5 ng mL-1, which was reached 0.5 h after the dose. At equihypotensive doses, captopril and nicardipine increased plasma renin activity markedly and slightly, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201532 TI - Evaluation of rectal mucosal irritation in rabbits after sub-chronic administration of lecithin-containing suppositories. PMID- 8201533 TI - The effects of a single dose of morphine on the concentration of substance P-like immunoreactivity in rat and guinea-pig brain. PMID- 8201534 TI - Glutaraldehyde cross-linked bovine casein microspheres as a matrix for the controlled release of theophylline: in-vitro studies. AB - A controlled release dosage form of theophylline in the form of microspheres using the milk protein casein as the matrix is described. Glutaraldehyde cross linking of an aqueous alkaline solution of the protein containing the drug, dispersed in a mixture of dichloromethane/hexane having ca. 1% of an aliphatic polyurethane as the suspension stabilizer, led to the formation of the drug loaded microspheres. Drug incorporation efficiency of around 80% could be achieved by the technique. Release profiles of the drug were examined in simulated gastric and intestinal fluids at 37 degrees C. It was observed that the release was diffusion-controlled and followed the Higuchi model. Release characteristics were influenced by the cross-linking density, particle size and the extent of loading. Data obtained indicate that the natural milk protein casein could be used as a matrix for sustained release oral dosage forms. PMID- 8201535 TI - Emotional distress and coping with a stressful relationship in adolescent boys. AB - The purpose of this analysis was to investigate relationships between emotional distress in middle and late adolescent boys and the strategies they use to cope with a stressful relationship. The sample of 130 boys was surveyed using the Personal Stress Inventory to assess emotional distress, the Jalowiec Coping Scale, and a demographics questionnaire. Parent was the most frequently reported stressful relationship, followed by girlfriend. Adolescents used more problem oriented coping (POC) than affective-oriented coping (AOC). AOC was a better predictor than was POC of emotional distress and predicted 56% of the variance in emotional distress scores. The findings provide nurses with information for identifying middle and late adolescent boys who are at risk for emotional distress. PMID- 8201536 TI - Parents coping with infants requiring home cardiorespiratory monitoring. AB - The investigator used a semistructured interview and McCubbin's Familial Invulnerability Test to examine how mothers and fathers cope with caring for a cardiorespiratory-monitored infant in the home. Content analysis of interview data showed that the persistent gravity of the situation and fears of incompetency in managing their infant's care, coupled with inadequate respite, were the greatest source of hardship for parents. Informational and emotional support from family members and professionals were resources used to manage this experience. Both emotion-focused and problem-focused strategies were used to cope with this situation. PMID- 8201538 TI - Coping strategies used by black school-age children from low-income families. AB - This study of black children from low-income families was based on a theoretical framework of poverty and the stress-coping process. The results validated the applicability to this sample of an instrument that measures children's coping strategies. Children's perceptions of the frequency of use and effectiveness of specific coping strategies differed significantly among the group, particularly between girls and boys. The relationship of these findings to those of previous research and the underlying theories are discussed. PMID- 8201537 TI - Ethical dilemmas in the high-risk nursery: wilderness experiences. AB - Ethical dilemmas in the high-risk nursery are similar to wilderness experiences. Reinforcers of these experiences for nurses include a lack of knowledge of ethics, communication failures, and the immediacy of the situation. Recommendations are presented to enable nurses to address these ethical dilemmas and to become more actively involved in the decision-making process. PMID- 8201539 TI - Neonatal and pediatric critical care: a call for collaboration. AB - Neonatal and pediatric critical care units are growing in size and complexity. Each unit is staffed by a highly specialized group of nurses. Although the units share many commonalities, the relationship between nurses in the neonatal and pediatric critical care units often is characterized by rivalry and antagonism rather than by cooperation. The purpose of this report is to identify similarities and differences between the two units and to describe the benefits of collaboration between units. PMID- 8201540 TI - Selected indicators of maternal child health in South Carolina. PMID- 8201541 TI - Ribavirin administration via scavenger vacuum systems in the treatment of respiratory syncytial virus (RSV). PMID- 8201542 TI - Collaborating with community hospitals for healthier babies through perinatal outreach education. PMID- 8201543 TI - [Development of highly selective synthetic methods utilizing arenetricarbonylchromium complexes and their application to syntheses of therapeutic agents]. AB - The development of new methodologies for the stereocontrolled synthesis of complex molecules is very important for the efficient synthesis of therapeutic agents. In this review, 1) the stereocontrolled synthesis of exocyclic olefins using arene.Cr(CO)3-catalyzed 1,4-hydrogenation of conjugated diene and its application to the synthesis of prostacyclin analogs, 2) new catalytic activities of arene.Cr(CO)3 as a hydrogenation catalyst, 3) the stereocontrolled synthesis of silyl dienol ethers and dienamides using arene.Cr(CO)3-catalyzed isomerization, and 4) a novel carbon-carbon bond-forming reaction through eta 5 pentadienylchromium complexes, are described. PMID- 8201544 TI - [Effect of Enterued administration on the intestinal absorption of orally active cefem antibiotics]. AB - The effect of simultaneous administration of Enterued, an elemental diet, which is composed of oligopeptides (egg white hydrolyzate), on the orally active cefems was investigated. Ceftibuten (CETB) administered together with Enterued to man was excreted slower in the urine. AUC from the plasma concentrations of CETB after the oral administration with Enterued was markedly decreased compared to that without Enterued in rat. In contrast, neither urinary excretion of cephalexin (CEX) in man nor the AUC from the plasma profile of CEX in rat was changed by Enterued. Furthermore, the disappearance, tissue accumulation, net absorption of CETB from the rat jejunal loop were significantly inhibited by Enterued. However, the net absorption of CEX has no alternation in the presence of Enterued, although the apparent disappearance decreased on the basis of the diminishment of tissue accumulation. Additionally, Hepan ED, which is an elementary diet composed of amino acids, and the mineral solution containing neither peptides nor vitamins have also exhibited the decreasing effect on the CETB absorption behaviour. These results suggested that the inhibitory effects of Enterued on the absorption of these antibiotics were not due to the inhibition of peptide-transport systems. PMID- 8201545 TI - [Crude drugs from aquatic plants. III. Quantitative analysis of triterpene constituents in alismatis rhizoma by means of high performance liquid chromatography on the chemical change of the constituents during alismatis rhizoma processing]. AB - As a series of study on the evaluation of Alismatis Rhizoma and the chemical characterization of the processing, a quantitative method by high performance liquid chromatography (HPLC) for ten triterpene constituents, alisols A, A monoacetate, B, B monoacetate, E 23-acetate, F, and G and 13,17-epoxyalisol A, 11 deoxyalisols B and B 23-acetate, has been developed. By the use of this HPLC method, the contents of these triterpenes in various Alismatis Rhizoma and the fresh rhizoma of Alisma oriental JUZEPC, originated from in China, Taiwan, and Japan were examined. Furthermore, the chemical change of the triterpene constituents during the drying process of the rhizoma of Alisma oriental has been investigated and it was found that the bioactive triterpenes of Alismatis Rhizoma such as alisol A and alisol A monoacetate were artificially formed during the drying process. PMID- 8201546 TI - [Anti-tumor promoting activities of kampo prescriptions. II. Inhibitory effects of souseiryu-to on two-stage carcinogenesis of mouse skin tumors and mouse pulmonary tumors]. AB - To search for possible anti-tumor promoters, we carried out a primary screening of fourteen kampo prescriptions utilizing their possible inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation which is induced by 12-O tetradecanoylphorbol-13-acetate (TPA). In these prescriptions, shouseiryu-to exhibited the most significant inhibitory effect on the EBV-EA activation. Furthermore, two-stage carcinogenesis of mouse skin tumors induced by 7,12 dimethylbenz[a]anthracene (DMBA) and TPA, and mouse pulmonary tumors induced by 4 nitroquinoline-N-oxide (4NQO) and glycerol were strongly inhibited to shouseiryu to. PMID- 8201547 TI - [Sustained-release effect of the direct compressed tablet based on chitosan and Na alginate]. AB - In the dissolution test of tablets prepared by the direct compression of chitosan with 10% sodium alginate (NaAlg), the release of theophylline was extended independently of the medium pH. The drug release mechanism of the tablet was investigated by measuring the dissolution behavior of such excipients as chitosan and NaAlg. It was shown that at the lower pH the drug release was accompanied with the dissolution of chitosan, while at the neutral pH it was controlled by the gelation and dissolution of NaAlg. Further more by the oral administration of the tablet to beagle dogs, the sustained release of theophylline was also confirmed by some bioavailability parameters. Thus the chitosan tablet with 10% NaAlg was expected to be a pH-independent sustained release dosage form. PMID- 8201548 TI - [Studies on the constituents of Scutellaria species. XV. On the diterpenoid constituents of the leaves of Scutellaria alpina L]. AB - From the leaves of Scutellaria alpina L., four new neo-clerodane diterpenes (1-4) were isolated. The structures of 1-4 were shown to be (4S)-19-acetoxy-8 beta hydroxy-6 alpha-benzoyloxy-4,18-epoxy-neo-cleroda-11,13- dien-15,16-olide, (4S) 19-acetoxy-8 beta-hydroxy-6 alpha-tigloyloxy-4,18-epoxy-neo-cleroda-11,13- dien 15,16-olide, (4S, 11S)-11-acetoxy-8 beta,19-dihydroxy-6 alpha-tigloyloxy-4,18 epoxy-neo- clerod-13-en-15,16-olide, and (4S)-19-acetoxy-8 beta-hydroxy-6 alpha, 7 beta-dibenzoyloxy-4,18-epoxy-neo- cleroda-11,13-dien-15,16-olide, respectively, by the chemical and spectral data. PMID- 8201549 TI - [Reaction of 3-aryl-2-nitroacrylates with titanium tetrachloride. Formation of 4H 1,2-oxazines and hydroxy-arylaldehydes]. AB - The reaction of ethyl 3-aryl-2-nitroacrylate (1a: aryl = 3-methoxyphenyl) with toluene in the presence of titanium tetrachloride gave 4-(4'-methyl-phenyl)-4H 1,2-benzoxazine (3) in a 44.2% yield. The acrylate 1a reacted with dichloromethane in the presence of titanium tetrachloride to give 5-methoxy salicylaldehyde (2a) in a 61.8% yield. Therefore, 2a was presumed to be formed via an intermediate 4H-1,2-benzoxazine (3'), followed by ring opening to quinone methide and cyano formate. In a similar reaction using both toluene and dichloromethane, 1 bearing a 2-naphthyl group gave a dimer of quinone methide and 1-hydroxy-2-naphthaldehyde via 4H-naphth[2,1-e]-1,2-oxazine, respectively. PMID- 8201550 TI - Soft tissue anchor systems. AB - The concept of soft tissue attachment and reattachment has been addressed over the years through a variety of surgical techniques. This includes tendons and ligaments that have been detached both surgically and traumatically from their osseous origins or insertions. This study is designed to provide the reader with a comprehensive overview of current commercially available devices. Detailed descriptions of the various devices are provided along with a discussion of the advantages and disadvantages of each. Their application and use in reconstructive foot and ankle surgery are also discussed. PMID- 8201551 TI - Lower extremity static and dynamic relationships with rearfoot motion in gait. AB - Twenty nonsymptomatic subjects were assessed while walking at a photoelectronically monitored place (2 +/- 0.1 m.s-1) using high speed cinematography (200 Hz) to record the rearfoot motion in the frontal plane, and electrogoniometry (100 Hz) to measure joint kinematics in the lower extremity. The foot type of the subjects was determined statically by using a podiascope and digitization techniques. The results demonstrated that no foot type variables contributed significantly to the variance in either rearfoot angle at foot strike or maximum rearfoot angle (p > 0.05). Regression equations were developed using kinematic variables: rearfoot angle at foot strike = 3.81 + (0.06*time to hip internal rotation) - (0.46*tibia internal rotation) + (0.14*plantarflexion); (R = 0.87, SE = 1.23 degrees); maximum rearfoot angle = 4.02 + (0.52*hip internal rotation) - (0.11*time to hip internal rotation); (R = 0.66, SE = 2.07 degrees). This study identifies hip joint movements as being the most significant contributors to prediction of rearfoot angles produced during walking. PMID- 8201552 TI - Atypical case of Becker's muscular dystrophy. Early identification and management. AB - A case of a child with Becker's muscular dystrophy is presented. Because of the genetic and clinical similarity with the more common Duchenne muscular dystrophy, these two diseases are compared. Since muscular dystrophy often initially presents with toe walking, flat-foot, and waddling gait, podiatrists may be the first physicians to see the child and provide early diagnosis. PMID- 8201553 TI - Isolated fracture of the lateral cuneiform. A rare tarsal injury. PMID- 8201554 TI - Magnetic resonance imaging of osteochondral lesions of the talar dome. PMID- 8201555 TI - Fish fin spine foreign body. PMID- 8201556 TI - Metatarsocuneiform coalition. AB - This was clearly a case of an unusual anomaly. Clinically, this was a case of an osseous coalition of congenital origin. Since the patient eventually became asymptomatic, no further treatment was necessary. Unfortunately, the patient's parents were unavailable to be radiographed to test the hereditary nature of this disorder. The radiographs and fluoroscopy films were sent to a radiologist. The radiology report stated a total and complete coalition (osseous fusion) between the third metatarsal base and the third cuneiform, with no indication of a joint space present in the left foot scan. Since this pathology is more of an incidental finding and caused the patient no discomfort, surgical correction was not necessary. Certainly, more coalitions of this nature may exist without patient knowledge. This case demonstrates another pathology that the podiatric physician may need to address. PMID- 8201557 TI - A look to the future is already here. PMID- 8201558 TI - Lens refilling and endocapsular polymerization of an injectable intraocular lens: in vitro and in vivo study of potential risks and benefits. AB - Endocapsular cataract removal and injection of a liquid artificial lens has several advantages, including restitution of accommodation, small corneoscleral incision, a more physiological position of the intraocular lens, and a reduced rate of secondary opacification. Our technique consists of bimanual phacofragmentation followed by injection of a fluid monomeric material that can be polymerized inside the capsular bag by short light exposure. Our study assessed the potential risks of the technique (e.g., heat damage to ocular tissue, light damage to the retina) and investigated the technique in vivo. We performed in vitro experiments on porcine cadaver eyes and an in vivo study on 15 rabbits. After a clinical follow-up of at least 12 weeks, the eyes were investigated histopathologically. During the polymerization process, the highest temperature measured at the posterior lens capsule was 45.1 degrees Celsius for a few seconds. The measured irradiance (0.065 watts per cm2) and the risk of photochemical damage to the retina during 20 seconds of polymerization were comparable to that caused by 1.5 minutes of standard coaxial illumination with the operating microscope. In vivo there were no serious inflammatory reactions except in four cases in which there had been intraoperative problems. The rate of secondary opacification appeared less than in conventional intraocular lens implantation in rabbits, especially when the capsule refilled completely. Retinal damage could not be detected histopathologically. In conclusion, refilling techniques may be successful once appropriate refilling materials become available. PMID- 8201559 TI - Performance of diffractive multifocal intraocular lenses in extracapsular cataract surgery. AB - In a prospective, randomized clinical trial, 42 patients received a monofocal intraocular lens and 38 a multifocal lens after extracapsular cataract extraction. Patients were examined three, six, and 12 months after surgery. Uncorrected visual acuity was 20/40 or better in 57% of monofocal and 58% of multifocal patients; 12% and 52% had near uncorrected visual acuity of J1 to J2, respectively. Best corrected visual acuities were not significantly different. Forty-eight percent of the multifocal and 8% of the monofocal group did not require spectacle correction. On a patient satisfaction questionnaire, 60% of all patients reported discomfort when using spectacles for near vision. Patients in the multifocal group were more satisfied with their near vision than those in the monofocal group. The difference in satisfaction was not significantly different although more multifocal patients reported visual phenomena (e.g., glare, halos). Mean contrast sensitivity for the monofocal group and the multifocal group was 1.73 and 1.70, respectively. At low contrast sensitivities, the difference was not significant although the monofocal patients scored better. PMID- 8201560 TI - Improving estimation of corneal refractive power by measuring the posterior curvature of the cornea. AB - We developed a formula to measure the posterior curvature of the cornea. In our study, real corneal power in 51 eyes was calculated by using anterior and posterior curvatures and corneal thickness. The corneal refractive index was found to be a variable value between 1.3243 and 1.3339 (mean 1.3304 +/- 0.0003). PMID- 8201561 TI - Refractive changes induced by electrocautery of the rabbit anterior lens capsule. AB - The pathologic basis for presbyopia is classically attributed to lenticular sclerosis or atrophy of the ciliary muscle, but recent work suggests that thickening and loss of elasticity of the anterior lens capsule play an important role. As no practical means for attenuating or reversing the aging process of lens protein has been identified, alteration of the lens capsule eventually might prove to be a desirable alternative to spectacle correction in presbyopic individuals. This paper describes changes in the refractive properties of the lens resulting from alteration of the anterior lens capsule by application of focal cautery, using both an in vitro, in situ and an in vivo rabbit model. In vitro thermal treatment (electrocautery) of the capsule significantly increased the anterior curvature of the lens by an average of +2.95 diopters. Histologic examination of the treated lenses showed thinning of the capsule in the treated areas, as well as focal vacuolar degeneration in the lens substance beneath the lesions. In vivo thermal treatment of eyes induced a significant shift toward myopia, compared with control eyes. The accommodative range increased post treatment relative to the controls, but the effect diminished over time, stabilizing near baseline at two to three weeks after treatment. Histologic examination showed localized changes but no signs of diffuse cataract formation. We conclude that the anterior capsule may play a significant role in the refractive power and accommodative changes in the crystalline lens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201562 TI - Efficacy of diclofenac sodium ophthalmic solution versus placebo in reducing inflammation following cataract extraction and posterior chamber lens implantation. AB - One hundred forty-eight patients were enrolled in a randomized, prospective, placebo-controlled clinical trial evaluating the efficacy of diclofenac sodium (Voltaren Ophthalmic) in reducing ocular inflammation following extracapsular cataract extraction with posterior chamber intraocular lens implantation. Eligible patients were enrolled and randomized (2:1 diclofenac:placebo) if the sum of anterior chamber cells plus flare one day postoperatively (baseline) was at least four. None of the patients received concomitant steroidal anti inflammatory treatment. The 99 patients receiving diclofenac sodium had significantly greater improvement from baseline in summed flare plus cell score than the 49 placebo patients at two to five days and seven to nine days after baseline. Similarly, diclofenac sodium patients had significantly less post baseline conjunctival erythema and ciliary flush than placebo patients. Significantly more diclofenac sodium patients than placebo patients showed moderate to marked improvement from baseline in overall assessment of inflammatory response. Forty-nine percent of placebo patients but only 17% of diclofenac patients were considered therapeutic failures (P < .001). By five to seven days, 82% of diclofenac sodium patients and 59% of placebo patients had corrected visual acuities of 20/40 or better (P < .001). There were no clinically important differences in mean intraocular pressure at any visit. PMID- 8201563 TI - Phacoemulsification with aspirated or retained Viscoat. AB - Endothelial cell counts, morphology, and 24-hour postoperative intraocular pressure (IOP) changes were measured in 55 consecutive patients (60 eyes) who had uncomplicated phacoemulsification and posterior chamber lens implantation with either aspirated (30 eyes) or retained (30 eyes) Viscoat (sodium chondroitin sulfate-sodium hyaluronate). The surgical technique was standardized in all cases. Endothelial cell loss was almost identical in the aspirated and in the retained groups (8.8% and 8.7%). Postoperative pleomorphism was significantly less in the retained Viscoat group than in the aspirated group, suggesting a possible protective effect of the retained viscoelastic. Corneal thickness increased significantly in the retained Viscoat group, but this was not significant clinically. The retained Viscoat group had more patients with a postoperative IOP greater than 30 mm Hg and a greater mean increase in postoperative IOP, although the difference between the groups was not significant. The IOP changes may have been caused by blockage of the trabecular meshwork by the retained Viscoat. The results suggest that Viscoat can be retained after cataract surgery if the surgeon is prepared for a greater 24-hour postoperative increase in IOP. PMID- 8201564 TI - Use of collagen shields in cataract surgery. AB - A randomized, prospective, multicenter study evaluated the efficacy and safety of using collagen shields to deliver drugs after cataract surgery. Collagen shields saturated with an antibiotic and a steroid were placed in 90 eyes postoperatively. A control group of 93 eyes received the same drugs through a peribulbar/retrobulbar injection. One day after surgery, the shield group had significantly less corneal edema, conjunctival hemorrhaging, and postoperative pain and fewer corneal opacities. All symptoms except the conjunctival hemorrhaging disappeared by day seven. Our study suggests that using collagen shields for drug delivery after cataract surgery decreases tissue damage and increases patient comfort without adverse side effects. PMID- 8201565 TI - Corneal lip tunnel incision. AB - To evaluate whether the corneal lip tunnel incision or the sutureless closure causes any refractive problems, we performed a retrospective study on 387 cataract surgery patients who were divided into four groups based on type of wound closure and whether the corneal lip was made. The four groups consisted of patients who received an X-stitch closure without the corneal lip, a horizontal mattress stitch without the lip, a horizontal mattress stitch with the lip, and a sutureless closure with the lip. All patients had phacoemulsification in situ; implantation of a foldable silicone lens was performed through a scleral tunnel incision. Clinical evaluations included preoperative characteristics and postoperative Snellen visual acuity, intraocular pressure, and vector analysis of cylinder. In all four groups, a 4.0 mm wide incision was used. Entrance into the clear cornea during the corneal lip tunnel incision did not induce additional cylinder, and the sutureless closure did not decrease induced cylinder or increase the against-the-rule shift. The results of this study indicate that the combination of a 4.0 mm incision with 1.5 mm corneal lip, phacoemulsification in situ, foldable lens implantation, and sutureless closure is a safe and effective procedure for cataract surgery. PMID- 8201566 TI - In vitro adhesion of Staphylococcus epidermidis on heparin-surface-modified intraocular lenses. AB - This quantitative study assessed the in vitro adhesion of Staphylococcus epidermidis on two types of intraocular lenses: conventional poly(methyl methacrylate) (PMMA) and heparin-surface-modified PMMA. Level adhesion was measured by microbiological turbidimetry. We also measured modifications in the bacterium's structural fatty acids after adhesion using gas chromatography. PMID- 8201567 TI - Quantitative assessment of corneal astigmatic surgery: expanding the polar values concept. AB - The purpose of astigmatic corneal surgery is to flatten the steeper meridian of the preoperative cylinder, to steepen the flatter meridian, or both. Therefore, it may be useful to quantitate the surgical effect by calculating the equivalent dioptric value of the postoperative cylinder in these principal meridians. In this study, the dioptric value projected on the preoperatively steeper meridian is termed the with-the-power (WTP) component, the portion projected on the flatter meridian, the against-the-power (ATP) component. Consider a preoperative net astigmatism of the power N in the meridian a. After astigmatic corneal surgery, the postoperative corneal cylinder is M in the meridian b. For the postoperative cylinder, the WTP component = M x sin2([b + 90]-a). The ATP component = M x cos2([b + 90]-a). The astigmatic polar value is defined as the difference between these magnitudes: AKP = M x (sin2[(b + 90)-a] - cos2[(b + 90) a]). By calculating the astigmatic polar value, the surgeon immediately knows the outcome of the surgical procedure (i.e., whether the preoperative astigmatism has been undercorrected, overcorrected, or perfectly corrected). We describe the theory behind this new formula and discuss its applications and limitations. PMID- 8201568 TI - Coring: a potential problem in eye surgery. AB - Any needle passing through a rubber stopper can aspirate a core of rubber. This rubber may then be injected into the eye or into the retrobulbar or peribulbar space. Aspirates from a number of syringes were spun down in a centrifuge and examined for microscopic particles. All specimens contained microscopic particles even from half-used bottles of Xylocaine. PMID- 8201569 TI - Changing practice patterns in refractive surgery: results of a survey of the American Society of Cataract and Refractive Surgery. AB - A questionnaire on refractive surgical practice was sent to the entire membership of the American Society of Cataract and Refractive Surgery in 1992. One thousand eight hundred and forty-one (1,841) of the 4,950 members returned the survey for a response rate of 37.2%. The questionnaire was designed to be self-administered and elicited information on types of refractive procedures performed in the survey year and the preceding year, as well as the intent to perform refractive procedures in the future. Surgeons who perform radial keratotomy (RK) increased from 22% in 1991 to 30% in 1992; 45% expected to perform RK in 1993-1994. The following categories of information were requested: characteristics of RK patients, techniques used by the surgeon, characteristics of the surgeon's overall practice, type of RK training, surgical outcome, and prevalence of complications. The results of this survey indicate that the use of RK and astigmatic keratotomy (AK), as well as other refractive procedures, is steadily increasing. Radial keratotomy was mainly performed on patients 20 to 49 years of age who had low to moderate myopia. The majority of surgeons used four to eight radials, centrally directed incisions, and single depth settings. Three quarters of the surveyed RK surgeons used the Casebeer nomogram. The survey results indicated that 42% of surgeons performing photorefractive keratectomy (PRK) did not perform RK or other refractive procedures, suggesting that growth in the practice of PRK following FDA approval may come from both current RK surgeons and novice refractive surgeons. PMID- 8201570 TI - Excimer laser phototherapeutic keratectomy for treatment of recurrent corneal erosion. AB - Two patients with a history of frequent recurrent corneal erosion for whom standard medical therapy was determined ineffective had phototherapeutic keratectomy (PTK) with an excimer laser. Before treatment, one patient had four episodes in a six-month period; the other had ten to 20 recurrences with four serious episodes in a seven-month period. After PTK, neither patient had a recurrence after 18 months follow-up. Subjectively, both patients felt the treated area healed faster than previous abrasions. Vision, refraction, keratometry, and corneal thickness measurements appeared unaffected by the treatment. PMID- 8201571 TI - Ultrasound biomicroscopic analysis of haptic position in late-onset, recurrent hyphema after posterior chamber lens implantation. AB - Late-onset, recurrent hyphema is an uncommon complication of posterior chamber intraocular lens implantation. Pathological studies and indirect clinical evidence, including iris transillumination defects and iris tucking, have implicated haptic-iris contact. The technique of high-resolution ultrasound biomicroscopy developed in our laboratories allows imaging of intraocular lens haptics and their relationship to surrounding structures. Examination of two cases with late-onset, recurrent hyphema revealed that the margins of the superior haptics were sulcus fixated and indenting the peripheral iris. Blood could be traced beneath the peripheral iris in one case. Our findings indicate that haptic-iris contact was the source of bleeding. Capsular fixation should make this complication less likely. PMID- 8201572 TI - Dislocation of a scleral-fixated, posterior chamber intraocular lens after fixation suture removal. AB - A 58-year-old man's posterior chamber intraocular lens dislocated after a transscleral fixation suture was removed during a routine eye examination. The lens had to be repositioned. A scleral flap over the fixation sutures and a better understanding by general ophthalmologists of transscleral fixation suturing would have prevented this complication. PMID- 8201573 TI - Capsulorhexis in the rabbit eye as a model for pediatric capsulectomy. AB - Continuous curvilinear capsulorhexis (CCC) is now a standard procedure in cataract surgery. In pediatric eyes, however, this technique is difficult to perform. Because of the elasticity and tension of the pediatric anterior lens capsule, the danger of radial tears is high. Similar conditions are found in the rabbit eye. The anterior lens capsule of young albino rabbits is very elastic. We developed a CCC technique in rabbits that allows a controlled round capsular opening. This technique was used in an experimental study with 16 rabbits (32 eyes). Mean capsulorhexis diameter was 4.9 mm +/- 0.9. A radial tear occurred in only two of 32 cases. The technique, which permits a controlled circular anterior capsulectomy for capsules with high surface tension and elastic properties, may be useful in pediatric cases. A clinical trial appears warranted. PMID- 8201574 TI - Pupilloplasty for small pupil phacoemulsification. AB - In the pupilloplasty technique, the surgeon creates multiple partial sphincterotomies and stretches the sphincterotomies to enlarge any inadequately dilated pupil so that phacoemulsification can be safely performed. The technique recovers excellent physiologic function and cosmesis postoperatively. PMID- 8201575 TI - Periocular local anesthesia: medial orbital as an alternative to superior nasal injection. AB - We developed a new technique, the medial orbital pericone local anesthetic block, that surgeons can use a secondary block when inferotemporal retrobulbar or peribulbar/periocular injection of local anesthetics results in incomplete anesthesia. Unlike secondary local injections placed in the superonasal quadrant of the orbit, our technique injects the anesthetic into the fat compartment of the nasal side of the globe, a site that is relatively avascular and lacks vital anatomic structures. In more than 15,000 patients, this method proved an effective, safe means of secondary block and promoted orbicularis oculi muscle akinesia. PMID- 8201576 TI - Consultation section. Patient had keratoplasty in right eye for decompensated Fuchs' dystrophy. PMID- 8201577 TI - Accuracy of intraoperative staging in colorectal cancer. AB - In 216 patients with colorectal adenocarcinoma 'operative' and 'final' staging using Duke's classification were compared. The overall 'accuracy' of operative staging was 66% with 17% of tumours understaged and 17% overstaged. The major error was found in nodal staging. If selective peroperative adjuvant therapy is to be considered, efforts should be directed to improve operative nodal staging. Any recommendation for adjuvant perioperative chemotherapy based on operative staging alone will result in a significant number of patients having unnecessary treatment. PMID- 8201578 TI - Right hemicolectomy and peritoneal lavage in missile injuries of the right colon. AB - Missile injury of the right colon is a serious condition. Extensive bowel damage and faecal soiling are the main problems in managing these cases. The operative management and complications of 50 cases of war injury of the right colon were studied. Resection with primary anastomosis and antibiotic peritoneal lavage was performed in all cases. Thirty-seven (74%) had associated injuries other than the right colon. 5/50 (10%) developed septicaemia. There were 4 infected wounds (8%), 2 cases of irreversible shock (4%), 2 patients with cellulitis of the abdominal wall (4%) and one patient (1%) with respiratory failure, bleeding stress ulcers, intraperitoneal abscess or chest infection, 5/50 (10%) died, only two (4.25%) of them from causes related to their colonic injury. Our experience proves that right hemicolectomy with primary end-to-end anastomosis and peroperative antibiotic peritoneal lavage is a safe one-stage method in managing missile injuries of the right colon with peritoneal faecal soiling. PMID- 8201579 TI - Delayed diagnosis of biliary leak due to bile duct division during cholecystectomy. PMID- 8201580 TI - New respiratory therapies in cystic fibrosis. PMID- 8201581 TI - Chronic sinusitis in cystic fibrosis. PMID- 8201582 TI - Oral bile acids in cystic fibrosis-associated liver disease. PMID- 8201583 TI - Non-adherence to treatment in cystic fibrosis. PMID- 8201584 TI - Standards of care for children with cystic fibrosis--a personal view. PMID- 8201585 TI - Early and late outcome of cystic fibrosis screening. PMID- 8201586 TI - 2-(3,4-Dichlorophenyl)-N-methyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1 pyrrolidinyl)ethyl]acetamide: an opioid receptor affinity label that produces selective and long-lasting kappa antagonism in mice. PMID- 8201587 TI - 3-[4-(1,2-Diphenylbut-1-enyl)phenyl]acrylic acid: a non-steroidal estrogen with functional selectivity for bone over uterus in rats. PMID- 8201588 TI - 1,3-Diarylindan-2-carboxylic acids, potent and selective non-peptide endothelin receptor antagonists. PMID- 8201589 TI - N-omega-fluoroalkyl analogs of (1R)-2 beta-carbomethoxy-3 beta-(4-iodophenyl) tropane (beta-CIT): radiotracers for positron emission tomography and single photon emission computed tomography imaging of dopamine transporters. PMID- 8201590 TI - Novel Asp32-replacement tetrapeptide analogues as potent and selective CCK-A agonists. AB - A series of novel CCK tetrapeptide analogues of the general formula Boc-Trp Lys(Tac)-N(R)-(CH2)nCON(R')Phe-NH2 (Tac = o-tolylaminocarbonyl), where R,R' = H or Me and n = 1-5, have been synthesized and tested. These analogues, which lack an acidic residue at the penultimate position, demonstrated surprisingly high CCK A receptor affinity and selectivity. The effect of N-methylation pattern on CCK-A receptor affinity showed consistent trends for analogues in which n = 1, 2, or 3, with the di-N-methylated analogues having the highest affinity in each case. However, none of these analogues had full agonist activity, as measured by percent maximal PI hydrolysis. Two conformationally constrained analogues also demonstrated high CCK-A receptor affinity and selectivity, as well as nearly maximal agonist activity. In addition, one of these conformationally-constrained analogues demonstrated anorectic activity in rats. PMID- 8201591 TI - CCK-A-selective tetrapeptides containing lys(N epsilon)-amide residues: favorable in vivo and in vitro effects of N-methylation at the aspartyl residue. AB - Previous structure-activity studies on a series of CCK-A selective tetrapeptide agonists, typified by A-71623 (Boc-Trp-Lys(CONH-Ph-o-Me)-Asp-(N-Me)Phe-NH2), have shown that replacement of the Lys(N epsilon-carbamoyl) substituent with N epsilon acyl substituents resulted in partial agonists with moderate to high affinities for the CCK-A receptor and that replacement of the C-terminal dipeptide with either (N-Me)Asp-Phe or (N-Me)Asp-(N-Me)Phe was highly favorable to in vitro and in vivo CCK activity. The present study demonstrates that although analogues in the epsilon-amide series that are N-methylated at the Phe position are weakly active or inactive in an in vivo rat appetite suppression assay, incorporation of (N-Me)Asp or (N-Me)Asp-(N-Me)Phe modifications in this series results in analogues with markedly improved in vivo activity. In in vitro assays, there is minimal effect of N-methylation pattern on binding affinity, whereas there is a trend toward improved functional activity in the phosphatidylinositol hydrolysis assay in analogues containing (N-Me)Asp. PMID- 8201592 TI - [L-Ala3]DPDPE: a new enkephalin analog with a unique opioid receptor activity profile. Further evidence of delta-opioid receptor multiplicity. AB - To investigate delta-opioid receptor topography near the 3-position of [D-Pen2,D Pen5]enkephalin (DPDPE), a series of small-group 3-position analogs of DPDPE have been synthesized and assayed for binding potencies and in vitro biological activities. L-Amino acid substitutions at this position are highly favored over D amino acid substitutions, with the smallest, [L-Ala3]DPDPE (DPADPE), being the most favored in the series investigated. [L-Ala3]DPDPE is nearly as delta-potent and more delta-selective in both rat brain binding (18 nM vs [3H] [p-ClPhe4]DPDPE and mu/delta = 610) and peripheral bioassays (12 nM in the MVD and GPI/MVD = 4500) when compared to DPDPE (8.5 nM, mu/delta = 73 and 4.1 nM, GPI/MVD = 1800, respectively). Whereas DPDPE is a potent analgesic when given icv, [L-Ala3]DPDPE is only a weak analgesic. However, [L-Ala3]DPDPE has been found to antagonize DPDPE, but not Deltorphin II, in a moderately potent (pA2 = 5.7) and selective fashion in vivo. Thus, [L-Ala3]DPDPE is a fairly potent agonist at peripheral delta receptors and is a moderately potent (mixed) antagonist of delta 1 receptors in the brain. It appears that [L-Ala3]DPDPE does not interact in any significant manner with delta 2 or mu receptors in the brain. PMID- 8201593 TI - DNA sequence-specific reading by echinomycin: role of hydrogen bonding and stacking interactions. AB - The binding of echinomycin to DNA hexamers of the form GpApXpZpTpC, where the central XpZ step can be CpG, TpA, GpC, or ApT, has been studied by molecular modeling and molecular mechanics techniques. Interaction energies have also been calculated for the complexation of echinomycin with sequences containing the preferred central CpG step and different flanking base pairs. Besides, two more sets of sequences incorporating either 2,6-diaminopurine (DAP) or hypoxanthine in place of adenine or guanine, respectively, have been examined. The aim of this work was to evaluate the relative importance of hydrogen-bonding and stacking interactions in the association of echinomycin with DNA and further rationalize the experimental evidence. The results of these calculations are in consonance with available data from footprinting experiments and appear to support our previous hypothesis that, in addition to the crucial intermolecular hydrogen bonds in the central region, the stacking interactions involving the quinoxaline 2-carboxamide chromophores of the drug and the DNA base pairs play an important role in modulating the binding specificity of this bisintercalating antitumor antibiotic. This is most clearly seen when sequences with similar minor-groove environments are compared (e.g. CpI vs TpA or CpG vs TpDAP). The dipole moment of N-methylquinoxaline-2-carboxamide has been measured (mu = 4.15 +/- 0.03 D) and compares very well with the calculated value (mu = 4.14 D). The fact that G:C, I:C, A:T, and DAP:T base pairs are shown to be endowed with distinct van der Waals and electrostatic stacking properties with respect to this heteroaromatic ring system could have important implications for the design of novel DNA mono- and bis-intercalating agents. PMID- 8201594 TI - Nitrobenzyl phosphorodiamidates as potential hypoxia-selective alkylating agents. AB - A series of novel nitrobenzyltetrakis(chloroethyl)phosphorodiamidates has been prepared, and its cytotoxicity has been evaluated against HT-29 cells under aerobic and hypoxic conditions and against murine bone marrow progenitor cells under aerobic conditions. All compounds were selectively toxic to HT-29 cells under hypoxic conditions, and the selectivity ratios varied from 1.6 to > 90. Analogs lacking either the nitro group or the tetrakis(chloroethyl) moiety were not cytotoxic, confirming that the presence of both nitro and incipient alkylating groups are essential for activity. Surprisingly, some analogs were far more toxic to bone marrow progenitors than to HT-29 cells under aerobic conditions, suggesting that other activation mechanisms must exist in these hematopoietic cells. Cytotoxicity increased with increasing depth in the HT-29 spheroid model, consistent with the preferential hypoxic toxicity of these compounds. Alkaline elution experiments showed a greater number of DNA interstrand cross-links under hypoxic compared to aerobic conditions. The extent of cross-linking in hypoxic cells was essentially identical to that produced by an equitoxic dose of melphalan, suggesting that the cytotoxicity of these compounds results from phosphorodiamidate release and alkylation of DNA. PMID- 8201595 TI - Synthesis and antitumor activities of novel 6-5 fused ring heterocycle antifolates: N-[4-[omega-(2-amino-4-substituted-6,7-dihydrocyclopenta [d]pyrimidin-5-yl)alkyl]benzoyl]-L-glutamic acids. AB - Novel antifolates with a 6-5 fused ring system, 6,7-dihydrocyclopenta [d]pyrimidine, (3a,b and 4a,b) were synthesized on the basis of combined modification of the heterocycle and bridge regions of the folate molecule. The synthetic method involves (1) synthesis of key intermediates of tert-butyl 4 [omega-(2-substituted-3-oxocyclopentanyl) alkyl]benzoates (8a,b and 9a,b) by a carbon-carbon radical coupling of tert-butyl 4-(omega-iodoalkyl)benzoates (7a,b) with 2-substituted-2-cyclopenten-1-ones (5 and 6) utilizing tributyltin hydride, (2) cyclization of either the methyl enol-ethers derived from the 2 cyanocyclopentanones (8a,b) or the 2-(methoxycarbonyl)cyclopentanones (9a,b) themselves by treatment with guanidine which leads to 6,7-dihydrocyclopenta [d]pyrimidines with a 4-(tert-butoxycarbonyl)phenylalkyl group (11a,b and 14a,b), (3) deprotection to the corresponding carboxylic acids (12a,b and 15a,b), and (4) amidation with diethyl glutamate and deesterification. Potent dihydrofolate reductase inhibition and highly potent cell growth inhibition were found with 2,4 diaminopyrimidine-fused cyclopentene compounds containing the trimethylene (3a) or ethylene bridge (3b) but not with the corresponding 2-amino-4-hydroxy analogs (4a,b). Compounds 3a and 3b were more growth inhibitory to several tumor cell lines (P388, colon 26, colon 38, and KB) than was methotrexate, with 3a being the most potent. Both 3a and 3b gave increases in the lifespan of P388 leukemic mice comparable to that observed with MTX. Both compounds were therapeutic against colon 26 colorectal carcinoma in mice. Compound 3a was highly effective against LC-6 non-small cell lung carcinoma in nude mice. PMID- 8201596 TI - A comparison of the cytotoxic and physical properties of aziridinyl quinone derivatives based on the pyrrolo[1,2-a]benzimidazole and pyrrolo[1,2-a]indole ring systems. AB - The cytotoxicity and physical properties of the pyrrolo[1,2-a] benzimidazole (PBI) and pyrrolo-[1,2-a]indole (PI) aziridinyl quinones were compared in order to assess the influence of the benzimidazole ring on antitumor activity and DNA reductive alkylation. Our studies show that the PI system possesses none of the cytotoxicity of the PBI systems. Unlike the PBIs, the PI system does not reductively alkylate DNA. Apparently, the benzimidazole ring favors reductive alkylation due to its electron deficient character compared to indole. In addition, the benzimidazole ring may provide the hydrogen bonding interactions required for the interaction with DNA. Our findings resulted in the elucidation of a PBI pharmacophore. Inspection of the literature revealed another drug sharing the PBI pharmacophore, 5-(1-aziridinyl)-3-(hydroxymethyl)- 2-(3-hydroxy-1 propenyl)-1-methyl-1H-indole-4,7-dione (EO9), which remarkably has cytotoxic properties similar to those of the PBIs. PMID- 8201597 TI - Non-peptide angiotensin II receptor antagonists: synthesis and biological activity of a series of novel 4,5-dihydro-4-oxo-3H-imidazo[4,5-c]pyridine derivatives. AB - A series of novel non-peptide angiotensin II receptor antagonists containing a 2,3,5-trisubstituted 4,5-dihydro-4-oxo-3H-imidazo[4,5-c]pyridine was prepared via several synthetic routes. Their affinity for angiotensin II receptors was established in a binding assay experiment and in an isolated-organ test. Molecules with small alkyl groups at C-2 and the (methylbiphenylyl)tetrazole moiety at N-3 were the preferred compounds with affinities and potencies in the nanomolar range. Variations at the N-5 position modulate the activity. Substitution at N-5 with various benzyl groups led to derivatives with in vitro potencies in the nanomolar range, which were equivalent to those of losartan in these assays. Replacement of the N-5 hydrogen with acetic acid esters or, in particular, acetamides gave molecules with increased activity. The most potent was 2-butyl-4,5-dihydro-4-oxo-3-[[2'-(1H-tetrazol-5-yl)-4- biphenylyl]methyl]-3H imidazo[4,5-c]pyridine-5- (N,N-diethylacetamide) (14u), which is superior to L 158,809 in vitro. Two prototypes were selected as their potassium salts for in vivo testing as antihypertensives. Compounds 14a (EMD 61,650) and 14q (EMD 66,684) reduced blood pressure dose dependently in spontaneously hypertensive rats when administered iv. In this assay, acetamide 14q is superior to losartan. PMID- 8201598 TI - Synthesis and carbonic anhydrase inhibitory activity of 4-substituted 2 thiophenesulfonamides. AB - A series of 4-substituted 2-thiophenesulfonamides was prepared from 3 thiophenecarboxaldehyde using metalation chemistry developed for 3-furaldehyde. Several of these compounds inhibit carbonic anhydrase II in vitro at concentrations of less than 10 nM. In addition, none of these compounds exhibit sensitization potential as determined from in vitro measurement of cysteine reactivity. PMID- 8201599 TI - Inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). 7. Development of a series of substituted N-phenyl-N'-[(1-phenylcyclopentyl)methyl]ureas with enhanced hypocholesterolemic activity. AB - We recently described our initial structure-activity relationship (SAR) studies on a series of N-phenyl-N'-aralkyl- and N-phenyl-N'-(1-phenylcycloalkyl)ureas as inhibitors of acyl-CoA: cholesterol acyltransferase (ACAT). From this series of analogs, compound 1 (PD 129337) was identified as a potent inhibitor of ACAT with an IC50 value of 17 nM. It was also shown to dose-dependently lower plasma cholesterol in cholesterol-fed rats. However, further investigation led to the suggestion that this compound was poorly absorbed, due to a lack of efficacy when administered by gavage in an aqueous vehicle. To overcome this deficiency, we continued our SAR study on this novel series of ACAT inhibitors using an acute in vivo screen in which the compounds are administered to rats in an aqueous, CMC/Tween suspension vehicle. Modification of the N'-phenyl moiety by incorporating functional groups which were amenable to forming salts and/or polar groups to reduce lipophilicity led to the identification of several inhibitors which displayed excellent efficacy employing this protocol. Overall, substitution on the phenyl ring in the ortho, meta, or para positions led to inhibitors with only a slight decrease in potency in vitro compared to the parent unsubstituted compound. Bulkier groups in the para position tended to lower the ACAT inhibitory activity in vitro. Polar groups, such as carboxyl (33,34), lowered in vitro activity significantly, suggesting that polar-ionic interactions are disfavored for the enzyme activity. From this series, compound 28 was evaluated further in secondary in vivo screens. In a chronic cholesterol-fed rat model of hypercholesterolemia, compound 28 dose-dependently reduced nonHDL cholesterol and significantly elevated HDL cholesterol. It showed significantly greater aqueous solubility than the parent compound 1. However, it was shown to cause adrenal toxicity in guinea pigs. This led us to design a series of homologs (44-51) with increased basicity and lower lipophilicity. Some of these compounds were more potent ACAT inhibitors in vitro and demonstrated excellent hypocholesterolemic activity in vivo. Interestingly, compound 45, unlike 28, did not produce adrenal toxicity in guinea pigs and demonstrated excellent lipid-modulating activity in the chronic model of preestablished dyslipidemia in rats. PMID- 8201600 TI - Antipsoriatic anthrones with modulated redox properties. 2. Novel derivatives of chrysarobin and isochrysarobin--antiproliferative activity and 5-lipoxygenase inhibition. AB - A novel series of 2- and 3-substituted 1,8-dihydroxy-9(10H)-anthracenones were synthesized and tested for their inhibitory activity against 5-lipoxygenase (5 LO) in bovine polymorphonuclear leukocytes and the growth of human keratinocytes. Structure-activity relationships are discussed with respect to the following redox properties of the compounds: reactivity against 2,2-diphenyl-1 picrylhydrazyl, generation of hydroxyl radicals as measured by deoxyribose degradation, and inhibition of lipid peroxidation in model membranes. Inhibition of cell proliferation seemed to be related to these properties, whereas 5-LO inhibition was not. Within a class of structural analogs the activity against 5 LO, which was markedly improved as compared to that of the antipsoriatic drug anthralin, correlated well with the overall lipophilicity. Even though a number of compounds in this series enhanced oxidative damage to nonlipid molecules such as deoxyribose, their antioxidant properties predominate in membrane lipids. Among the prooxidant compounds were also the most potent antiproliferative agents (IC50 values in the 10(-7) M range). PMID- 8201601 TI - Molecular structures and conformational studies of triarylcyclopropyl and related nonsteroidal antiestrogens. AB - Molecular structures and conformational characteristics of a series of 1,1 dichloro-2,2,3-triarylcyclopropanes (DTACs), which were reported previously to be distinctly antiestrogenic and inhibitors of the estrogen-receptor-positive MCF-7 human breast cancer cells in culture, are reported. In addition, structural and conformational features of the DTACs were compared to the first-known nonsteroidal antiestrogen, MER25, and the clinically useful antiestrogen Tamoxifen. The molecular structures of four DTAC compounds were determined by X ray diffraction. Crystallographic structures show that the DTAC molecules have nearly the same relative conformation for the three aryl rings which is designated as a "nonpropeller" conformation in contrast to the observed "propeller" conformation for the three rings in all known triarylethylenes. Systematic conformational searches were performed to find the conformational preferences of DTACs, MER25, and Tamoxifen using idealized model compounds built from their respective crystal structure. Energy-minimization and conformational search studies demonstrated that all DTAC molecules have a common, single global minimum energy conformer for their central core containing the dichlorotriarylcyclopropyl system, which is similar to that found in their crystal structures. Conformational search of MER25 showed that the molecule can assume a number of low-energy conformers of which two, one anti (A1) and one gauche (G1A), have about the same energy. The anti conformation is similar to the one observed in its crystal structure and resembles the estrogenic E-isomer of Tamoxifen, while the lowest energy gauche conformer of MER25 resembles more closely the antiestrogenic Z-isomer of Tamoxifen. NMR spectroscopic analysis of MER25 showed that the molecule exists predominantly in the anti conformation in solution. A comparative review of the structural features and bioactivities of Tamoxifen, DTACs, and MER25 provides a possible explanation for their low estrogen receptor binding affinity which is common to these compounds together with their antiestrogenic activity. PMID- 8201602 TI - C-glycosyl bond conformation in oxazofurin: crystallographic and computational studies of the oxazole analogue of tiazofurin. AB - Oxazofurin is the inactive oxazole analogue of the C-glycosyl thiazole antitumor agent tiazofurin. Replacement of the thiazole sulfur in tiazofurin with the oxazole oxygen in oxazofurin produces conformational effects that are examined using crystallographic and computational methods. The crystal structure of oxazofurin contains six molecules in the asymmetric unit and has been refined to a standard R value of 6.8% for all data. The six oxazofurin conformers show an average C-glycosidic torsion angle of 70(9) degrees. This value is significantly higher than the average absolute C-glycosidic torsion angle of 24(10) degrees obtained from previous thiazole nucleoside structures. Previous studies suggest that, in tiazofurin, an electrostatic interaction between a positively charged thiazole sulfur and negatively charged furanose oxygen constrains the C glycosidic torsion angle to a relatively small value. Ab initio molecular orbital studies presented here suggest that the higher C-glycosidic angles observed in the oxazofurin structures result from a repulsive interaction between negatively charged oxazole and furanose oxygens. Thus, it is likely that differences in activity between oxazo- and tiazofurin are either (1) due directly to differences in electronic properties between the thiazole and oxazole rings or (2) due to the variation in C-glycosidic bond conformation resulting from the alteration in the charge distribution of the heterocycle. PMID- 8201603 TI - Structural studies on bioactive compounds. 23. Synthesis of polyhydroxylated 2 phenylbenzothiazoles and a comparison of their cytotoxicities and pharmacological properties with genistein and quercetin. AB - A series of polyhydroxylated 2-phenylbenzothiazoles 3 has been prepared by demethylation of the precursor methoxylated 2-phenylbenzothiazoles 9. The key step in the construction of the benzothiazole nucleus involves a Jacobson cyclization of methoxylated thiobenzanilides 8. The target compounds inhibit WiDr human colon tumor cells and MCF-7 human mammary tumor cells in vitro with IC50 values in the low micromolar range, but the activity against MCF-7 cells is not related to estrogen receptor-binding affinity. None of the compounds showed selective cytotoxicity against Abelson virus-transformed ANN-1 cells encoded with the pp120gag-abl tyrosine kinase compared with the parental 3T3 line. Compounds were only marginally inhibitory to the EGF receptor-associated protein tyrosine kinase from a membrane preparation of A431 cells. The most active compound was 4,6-dihydroxy-2-(4-hydroxyphenyl)benzothiazole (3b) which has the same overall hydroxyl substitution pattern as genistein (1a). The compounds were weakly cytotoxic for an EGF receptor, overexpressing cell line HN5, but when tested for differential toxicity against the EGF receptor tyrosine kinase or the PDGF receptor tyrosine kinase in a standard mitogenesis assay utilizing human fibroblasts, no discrimination was observed. In this assay, the compounds inhibited DNA synthesis when added to cells during S phase. This suggests that inhibition could not be interpreted in terms of tyrosine kinase inactivation but more likely as a relatively broad specificity for the ATP-binding domain of other kinases such as thymidine kinase. PMID- 8201604 TI - Selective type IV phosphodiesterase inhibitors as antiasthmatic agents. The syntheses and biological activities of 3-(cyclopentyloxy)-4-methoxybenzamides and analogues. AB - The syntheses and biological activities of a number of benzamide derivatives, designed from rolipram, which are selective inhibitors of cyclic AMP-specific phosphodiesterase (PDE IV), are described. The effects of changes to the alkoxy groups, amide linkage, and benzamide N-phenyl ring on the inhibition of the cytosolic PDE IV from pig aorta have been investigated. As a result, some highly potent and selective PDE IV inhibitors have been identified. The most potent compounds have been further evaluated for their inhibitory potencies against PDE IV obtained from and superoxide O2- generation from guinea pig eosinophils in vitro. Selected compounds have also been examined for their activities in inhibiting histamine-induced bronchospasm in anaesthetized guinea pigs. 3 (Cyclopentyloxy)-N-(3,5-dichloro-4-pyridyl)-4-methoxybenzamide (15j) showed exceptional potency in all tests and may have therapeutic potential in the treatment of asthma. PMID- 8201605 TI - Presynaptic cholinergic modulators as potent cognition enhancers and analgesic drugs. 1. Tropic and 2-phenylpropionic acid esters. AB - Previous studies have shown that (R)-(+)-hyoscyamine has analgesic activity as a consequence of increased ACh release following antagonism of central muscarinic autoreceptors. Since the enhancement of central cholinergic transmission could be beneficial for cognitive disorders, we manipulated (R)-(+)-hyoscyamine, synthesizing several derivatives of tropic and 2-phenylpropionic acids, with the aim of obtaining drugs which are able to increase ACh release and consequently to show analgesic and nootropic activities. The results showed that several new compounds are indeed potent analgesics (with an analgesic efficacy comparable to that of morphine) and that the most potent one ((+/-)-19, PG9) also has remarkable cognition-enhancing properties. Our study confirmed that the mechanism of action involves ACh release even if it is still unclear whether only muscarinic autoreceptors or, also, heteroreceptors are involved. PMID- 8201606 TI - Presynaptic cholinergic modulators as potent cognition enhancers and analgesic drugs. 2. 2-Phenoxy-, 2-(phenylthio)-, and 2-(phenylamino)alkanoic acid esters. AB - Further modifications of the leads ((R)-(+)-hyoscyamine and (p chlorophenyl)propionic acid alpha-tropanyl ester), which show analgesic and nootropic activities as a consequence of increased central presynaptic ACh release, are reported. 2-Phenoxy- and 2-(phenylthio)alkanoic acid esters showed the best results. Several members of these classes possess analgesic properties which are comparable to that of morphine and at the same time are able to reverse dicyclomine-induced amnesia. Confirmation was found that the mechanism of action is due to an increase in ACh release at central muscarinic synapses and that both auto- and heteroreceptors controlling ACh release are very likely involved. According to the results obtained with (R)-(+)-hyoscyamine, analgesic activity is stereochemistry dependent, since the R-(+)-enantiomers are always more efficacious than the corresponding S-(-)-ones. On the basis of their potency and acute toxicity, compounds (+/-)-28 (SM21) and (+/-)-42 (SM32) were selected for further study. PMID- 8201607 TI - 2-Alkynyl derivatives of adenosine-5'-N-ethyluronamide: selective A2 adenosine receptor agonists with potent inhibitory activity on platelet aggregation. AB - A series of new 2-alkynyl and 2-cycloalkynyl derivatives of adenosine-5'-N ethyluronamide (NECA) and of N-ethyl-1'-deoxy-1'-(6-amino-2-hexynyl-9H-purin-9 yl)-beta-D- ribofuranuronamide (1, HE-NECA), bearing hydroxy, amino, chloro, and cyano groups in the side chain, were synthesized. The compounds were studied in binding and functional assays to assess their potency for the A2 compared to A1 adenosine receptor. The presence of an alpha-hydroxyl group in the alkynyl chain of NECA derivatives accounts for the A2 agonist potency, leading to compounds endowed with sub-nanomolar affinity in binding studies. However, these analogues also possess good A1 receptor affinity resulting in low A2 selectivity. From functional experiments the 4-hydroxy-1-butynyl (6) and the 4-(2-tetrahydro-2H pyranyloxy)-1-butynyl (16) derivatives appear to be very potent in inducing vasorelaxation without appreciable effect on heart rate. The new compounds were also tested as inhibitors of platelet aggregation induced by ADP. Introduction of an alpha-hydroxyl group in the alkynyl side chain caused a greater increase in antiaggregatory activity than either NECA or HE-NECA, resulting in the most potent inhibitors of platelet aggregation so far known in the nucleoside series. The presence of an alpha-quaternary carbon such as the 3-hydroxy-3,5-dimethyl-1 hexynyl (12) and the 3-hydroxy-3-phenyl-1-butynyl (15) derivatives markedly reduced the antiaggregatory potency without affecting the A2 affinity. The hydrophobicity index (k') of the new nucleosides barely correlated with the binding data, whereas high k' values were associated with increased A2 vs A1 selectivity but with reduced activity in all functional assays. Some of the compounds synthesized possess interesting pharmacological properties. Compounds having an appropriate balance between vasorelaxation and antiplatelet activity, if confirmed in vivo, deserve further development for the treatments of cardiovascular disorders. PMID- 8201608 TI - Molecular similarity, quantitative chirality, and QSAR for chiral drugs. AB - The current policy of drug regulatory authorities demanding that pharmaceutical companies justify their reasons for preferring drugs containing a mixture of enantiomers over one stereoisomer increases the importance of quantitative structure-activity relations (QSARs) for chiral drugs. The QSAR proposed by Pfeiffer for chiral drug enantiomer potencies was brought into question by the existence of sets obeying an anti-Pfeiffer rule. Using computer-aided molecular design methods and treating chirality not as an existing/nonexisting property but as a continuous one improve the QSAR proposed by Pfeiffer, yielding higher correlation coefficients and an independent ordinate. Calculated shape similarities reveal the details of the Pfeiffer behavior and the source of the anti-Pfeiffer behavior. Consequently revised models for the D2 and sigma receptor are suggested. PMID- 8201609 TI - Relaxation and music therapies for asthma among patients prestabilized on asthma medication. AB - One hundred six asthmatic subjects were medically prestabilized, then assigned to eight sessions of progressive relaxation, music, or a waiting-list. Seventy-two subjects completed treatment, of which 37 were evaluated in the laboratory with measures of forced expiratory flow. Relaxation-group subjects reported feeling the most deeply relaxed and produced the greatest improvement in forced expiratory flow during the last presession assessment period. All groups evidenced decreases in asthma symptoms. All groups showed decreases in pulmonary function immediately after relaxation sessions. None of the changes in pulmonary function reached levels that are accepted in drug trials to be of clinical significance, and the therapeutic changes occurred only in the situation where training was rendered. Listening to music produced greater decreases in peaks of tension than progressive relaxation, and it produced greater compliance with relaxation practice, but it did not produce any specific therapeutic effects on asthma. PMID- 8201610 TI - Coping styles, opioid blockade, and cardiovascular response to stress. AB - We investigated the hypothesis that the effects of Monitoring and Blunting coping styles are mediated in part by endogenous opioids. Mean arterial pressure (MAP) and heart rate (HR) were measured in 39 males before, during, and after a mental arithmetic stressor. Each subject experienced the protocol once under opioid blockade (naltrexone) and once in a placebo condition, in counterbalanced order. Monitoring and Blunting were assessed using the Miller Behavioral Style Scale. High Blunting and high Monitoring were both associated with poorer MAP recovery under opioid blockade than in the placebo condition. Similar effects were noted for Blunting on the measure of HR. These results indicate that the coping styles of Monitoring and Blunting may be associated with enhanced opioid mediation of cardiovascular recovery from stress. PMID- 8201611 TI - Coping with chemotherapy for breast cancer. AB - Relations among coping, physical symptoms, and affect were investigated in 43 women undergoing adjuvant chemotherapy for breast cancer. Patients were assessed at the same point in their treatment so that the time for which coping was reported would be equivalent across individuals. Patients were asked how they coped specifically with chemotherapy, rather than how they coped with cancer in general, to make the domain specific. Positive and negative affect were assessed separately, using a scale free of somatic content. Relations between coping and affect were consistent with prior studies that have employed a general approach to assessing coping. Coping correlates of positive and negative mood differed. When the relations between physical symptoms and affect were examined, physical symptoms were related to negative affect but not to positive affect. Findings are discussed in terms of their implications for coping with cancer as well as their implications for the general coping literature. PMID- 8201612 TI - Anger expression and chronic pain. AB - Intensity of angry feelings and styles of expressing anger were examined for their relationship to measures of the chronic pain experience. Subjects were 142 chronic pain patients. Multiple regression analyses revealed that a style of inhibiting the expression of angry feelings was the strongest predictor of reports of pain intensity and pain behavior among a group of variables including demographics, pain history, depression, anger intensity, and other styles of anger expression. In a similar manner anger intensity contributed significantly to predictions of perceived pain interference and activity level. More conservative hierarchical regression analyses supported these findings. Results are consistent with explanatory models of pain and disability that hypothesize an etiologic role of a pervasive inability to express intense negative emotions, particularly anger. PMID- 8201613 TI - John Henryism and blood pressure in black college students. AB - Previous research on John Henryism, a coping mechanism linked to hypertension in blacks, has focused almost exclusively on rural, low-socioeconomic status (SES), adult populations. Furthermore, these studies have not evaluated mediating influences of John Henryism except in terms of SES. The primary focus of the current investigation was to examine the influence of John Henryism on cardiovascular disease risk factors among a relatively healthy sample of 421 urban, black college students. A second component of the study was to determine the role of social support as a mediating influence on those with limited coping resources and high John Henryism scores. Approximately 30% of males and 9% of females had systolic blood pressures > or = 140 mm Hg or diastolic blood pressures > or = 90. Females had higher John Henryism scores than males. John Henryism was also correlated with social support in females. Gender-specific regression models revealed that John Henryism was not an independent predictor of blood pressure in black college students. The results are discussed in terms of apparent gender differences with regard to overall coping mechanisms in black students and possible explanations for the lack of a John Henryism-blood pressure relationship in this population. PMID- 8201615 TI - Differences in pulse rate and heart rate and effects on the calculation of heart rate reactivity during periods of mental stress. AB - Heart rate and reactivity from pulse and ECG were compared over rest and mental arithmetic periods of 2-min duration each for 32 males and 50 females. Data from the two sources of heart rate were not significantly different during the rest period but did differ significantly during periods of heart rate acceleration and deceleration. Sex effects were also noted, with females having consistently higher heart rates from both sources of measurement. Calculation of heart rate reactivity via five procedures based upon the wider literature revealed significant differences between data from different sources of heart rate. Implications for assessment of heart rate reactivity to laboratory stressors are discussed, with suggestions for future research. PMID- 8201614 TI - Psychological and social effects of orthodontic treatment. AB - Adolescents with commonly occurring forms of malocclusion often are presumed to be at risk for negative self-esteem and social maladjustment. A randomized control group design was used to assess the psychosocial effects of orthodontic treatment for esthetic impairment. Ninety-three participants, 11 to 14 years old, with mild to moderate malocclusions, were randomly assigned to receive orthodontic treatment immediately or after serving as delayed controls. A battery of psychological and social measures was administered before treatment, during treatment, and three times after completion of treatment, the last occurring one year after termination. Repeated measures analyses of variance assessed group differences at the five time points. Parent-, peer-, and self-evaluations of dental-facial attractiveness significantly improved after treatment, but treatment did not affect parent- and self-reported social competency or social goals, nor subjects' self-esteem. In summary, dental-specific evaluations appear to be influenced by treatment, while more general psychosocial responses are not. PMID- 8201616 TI - The molecular cloning and characterization of Drosophila melanogaster myosin-IA and myosin-IB. AB - In this paper we describe the isolation and characterization of myosin-IA and myosin-IB, two distinct class I myosins from Drosophila melanogaster. A polymerase chain reaction based strategy using degenerate primers directed against two highly-conserved regions in the head domain of most myosins resulted in the isolation of these two novel myosins-I in addition to a number of previously identified myosins from three Drosophila cDNA libraries. A approximately 3.9 kilobase cDNA clone encoding the putative full-length myosin-IA gene product was isolated from an early embryonic library. Its deduced amino acid sequence predicts a protein of 1011 residues (117,094 Da) with a typical although highly basic myosin head, a neck composed of two IQ motifs, and a unique tail. A approximately 3.4 kilobase cDNA clone encoding the putative full-length myosin-IB gene product was isolated from an adult head library. Its deduced amino acid sequence predicts a protein of 1026 residues (117,741 Da) with a canonical head, three IQ motifs constituting the neck, and a distinct tail. Although both are myosins-I from fly, myosin-IA at cytological locus 31D-F and myosin-IB at cytological locus 61F appear to be more similar to their vertebrate homologs than they are to each other. Primary sequence analyses of both the head and tail domains of the known class I myosins illustrate a division of the metazoan myosin I family into four distinct subclasses with myosin-IA and myosin-IB as members of two of these groups. Just as the sequence comparisons demonstrate a disparity between myosin-IA and myosin-IB, Northern blot analysis of these two unconventional myosins indicates distinct patterns of temporal expression. PMID- 8201617 TI - Conserved sequences in a class of rare eukaryotic nuclear introns with non consensus splice sites. AB - Eukaryotic nuclear genomes contain a rare class of pre-mRNA introns with consensus sequence features that differ markedly from most pre-mRNA introns. Four genes have so far been identified that contain one copy each of this rare intron class in addition to several standard introns. These introns and homologous introns from several species were compared to identify conserved sequence elements and to establish consensus sequences for these elements. The only well conserved elements are found at the 5' and 3' ends of the introns. The 5' splice site sequence is ATATCCTT beginning with the first nucleotide of the intron and is invariant in the introns examined to date. The 3' splice site consensus sequence is YCCAC ending at the last nucleotide of the intron. An almost invariant sequence of TCCTTAAC is also found near the 3' end of the intron (the 3' upstream element). The length of the introns varies between 95 and 2940 nucleotides. The sequence organization of these introns suggests that they represent a variant class of pre-mRNA introns that might be spliced via a spliceosome mechanism employing factors distinct from those used by other pre mRNA introns. A search of small nuclear RNA (snRNA) sequences for regions complementary to the conserved elements of this rare class of introns found a strong match between U12 snRNA and the 3' upstream element and a weaker match between U11 snRNA and the 5' splice site sequence. PMID- 8201618 TI - Multiple folded conformations of a hammerhead ribozyme domain under cleavage conditions. AB - The conformation of a hammerhead ribozyme domain, formed between a 35-mer ribozyme and its 14-mer substrate, was studied under cleavage conditions with non cleavable substrate analogues. Each analogue substrate contained a single 2' deoxy-4-thiouridine that formed specific intermolecular crosslinks within the ribozyme-substrate complex upon irradiation with 365 nm light. The residues at positions 7 and 8 to 9 (the cleavage site) were found in contact with several bases of the ribozyme 5' conserved region regardless of whether the substrate was all-RNA, with a single deoxynucleotide at the cleavage site, or all-DNA. These contacts were observed in the presence of either 20 mM Mg2+ or 200 mM Na+. The multiple crosslinks generated between the ribozyme central core and each of the three substrates suggest the existence of several folded conformers of the ribozyme. A ribozyme mutation (A28U), which abolishes the catalytic activity, was shown to strongly affect the pattern of crosslinks; this argues for the presence of multiple folded conformers of the ribozyme some of which may be catalytically inactive. PMID- 8201619 TI - Structure determination of cucumber green mottle mosaic virus by X-ray fiber diffraction. Significance for the evolution of tobamoviruses. AB - Cucumber green mottle mosaic virus (CGMMV) is a rod-shaped virus of the tobacco mosaic virus (TMV) group. The structure of cucumber green mottle mosaic virus has been determined by fiber diffraction methods at 3.4 A resolution, and refined by molecular dynamics methods to an R factor of 0.093. Disassembly of TMV is driven by the mutual repulsion of intersubunit carboxyl-carboxylate pairs, but one of these pairs is not conserved in CGMMV. An alternative pair, located about 5 A from the site of the TMV pair, has been found in CGMMV. Comparison of the two structures suggests that the carboxylate groups are free to migrate in the subunit interfaces during evolution. PMID- 8201620 TI - Nerve growth factor in different crystal forms displays structural flexibility and reveals zinc binding sites. AB - Murine beta-nerve growth factor (beta NGF) is a 118 amino acid residue polypeptide which, as a functional dimer, plays an important role in the survival and development of certain neuronal populations. The structure of the bis desocta1-8 form of murine beta NGF has been determined in two different crystal modifications using X-ray methods. The two crystal forms, with space groups P2(1)2(1)2(1) and C2, were grown from 18 to 20% polyethylene glycol 8000 and 100 mM Pipes (pH 6.1) with zinc acetate concentrations of 1 mM and 100 mM, respectively. The C2 structure was solved by multiple isomorphous replacement using four heavy-atom derivatives and was refined to a crystallographic residual of 17.9% and 2.5 A resolution. The crystals contain three beta NGF monomers per asymmetric unit. Two monomers form a dimer related by a non-crystallographic 2 fold axis of symmetry. The third monomer also forms a dimer that is very similar, but with a crystallography related monomer as a partner. The electron density clearly defines residues 12 through 115 for all three monomers but the extreme N and C-terminal residues (9 to 11, 116 to 118) are ill defined in some cases. The P2(1)2(1)2(1) structure was solved by molecular replacement using the C2 structure as a search model and was refined to a crystallographic residual of 19.7% at 2.8 A resolution. This crystal form contains two monomers per asymmetric unit, again arranged as a non-crystallographic 2-fold-related dimer. The N and c termini are also variably defined. The core of each of the five monomers, which forms a cysteine knot motif, is very similar in all structures. Also, the dimer structures are very similar to one another, whether the monomers are related by crystallographic or non-crystallographic symmetry. However, three of the four loop regions that extend from the core of each monomer display substantial variability in conformation, even between monomers of the same dimer. This structural variability in the putative receptor binding regions suggests that structural malleability might be important in allowing the ligands to bind to different receptors with different affinities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201621 TI - The proton transfers in the cytoplasmic domain of bacteriorhodopsin are facilitated by a cluster of interacting residues. AB - The stepwise internal proton transfer reactions across the membrane, and the release and uptake at the surface, are the elementary steps that together constitute the transport mechanism in a proton pump. Although the proton donor and acceptor residues can be usually identified, the directionality and the energetics of the proton transfer must be determined to a large extent also by interactions of these with neighboring groups. We have examined the roles of residues D96, T46 and R227 in proton transfers during the photocycle of bacteriorhodopsin near its cytoplasmic surface, and in general the relationship between the reprotonation of the Schiff base and the subsequent proton uptake from the cytoplasmic side. The phenotypes of single and double mutants suggest close functional interaction among D96, T46, R227, and probably internal bound water. Measurements of the free energies of activation indicate that mechanistic interpretation of the rates changed by residue replacements is hindered by a general tendency toward lowered activation enthalpies in the mutated proteins. There is less ambiguity in the free energy levels of the photointermediates. It appears from these that the inhibitory and stimulatory influences of T46 and R227, respectively, on D96 as a proton donor compensate one another and ensure the effective reprotonation of the Schiff base. T46 and D96 mediate, in turn, proton uptake at the cytoplasmic surface. Although ultimately this will reprotonate D96, the observation of proton uptake from the bulk in R82Q without reprotonation of the aspartate residue suggests that the direct proton acceptor is not D96. The results thus indicate that the passage of the proton from the surface to the Schiff base is facilitated by multiple residue and water interactions in the cytoplasmic domain. PMID- 8201622 TI - Structures of three human beta alcohol dehydrogenase variants. Correlations with their functional differences. AB - The three-dimensional structures of three variants of human beta alcohol dehydrogenase have been determined to 2.5 A resolution. These three structures differ only in the amino acid at position 47 and the molecules occupying the alcohol binding site. Human beta 1 alcohol dehydrogenase has an Arg at position 47 and was crystallized in a complex with NAD(H) and cyclohexanol. A naturally occurring variant of beta 1 alcohol dehydrogenase, found in approximately 50% of the Asian population, possesses a His at position 47 (beta 2 or beta 47H) and was crystallized in a complex with NAD+ and the inhibitor 4-iodopyrazole. A site directed mutant of beta 1 alcohol dehydrogenase in which a Gly is substituted for Arg47 (beta 47G) was crystallized in a complex with NAD+. By comparing both the common and unique features of these structures, it is clear that position 47 contributes significantly to the strength of protein-coenzyme interactions. The substitution of Arg47 by His produces an enzyme with a 100-fold lower affinity for coenzyme, but creates no large changes in the enzyme structure. The substitution of Arg47 by Gly produces an enzyme with coenzyme binding characteristics more similar to the wild-type enzyme than to the enzyme with His at position 47, but the structure of the Gly47 variant exhibits differences in and around the coenzyme binding site. These changes involve a rigid-body rotation of the catalytic domain towards the coenzyme domain by approximately 0.8 degrees and local rearrangements of amino acid side-chains, such as a 1.0 A movement of Lys228, relative to the beta 1 enzyme. These structural alterations may compensate for the loss of coenzyme interactions contributed by Arg47 and can explain the high affinity of the Gly47 variant for coenzyme. PMID- 8201623 TI - Crystallization and preliminary X-ray analysis of restriction endonuclease BamHI DNA complex. AB - Restriction endonuclease BamHI from Bacillus amyloliquefaciens has been co crystallized with a 12 bp DNA fragment that encompasses its recognition site. The co-crystals diffract to at least 1.95 A resolution and belong to space group P2(1)2(1)2(1). The unit cell parameters are a = 108.8 A, b = 81.9 A, c = 68.8 A, consistent with one complex in the crystallographic asymmetric unit. The direction of the DNA appears to be along the b axis. In order to achieve end to end stacking of DNA, the complex must lie on the screw axis along b. A self rotation function has determined the directions of the non-crystallographic 2 fold axes. PMID- 8201624 TI - Nucleotide sequence of the Escherichia coli K12 histidine operon revisited. AB - We report on a significant difference between the published nucleotide sequence of the Escherichia coli K12 histidine operon and our sequencing results repeatedly obtained from a number of different E. coli K12 strains. The discrepancies include 39 base-pair changes and one addition located predominantly in the proximal portion of the operon. Our data also suggest that neutral and near-neutral mutations do not accumulate to a significant extent in the histidine operon of E. coli strains harbouring strong mutator alleles. PMID- 8201625 TI - Endogenous neuroprotection factors and traumatic brain injury: mechanisms of action and implications for therapy. AB - Throughout evolution the brain has acquired elegant strategies to protect itself against a variety of environmental insults. Prominent among these are signals released from injured cells that are capable of initiating a cascade of events in neurons and glia designed to prevent further damage. Recent research has identified a remarkably large number of neuroprotection factors (NPFs), whose expression is increased in response to brain injury. Examples include the neurotrophins (NGF, NT-3, NT-5, and BDNF), bFGF, IGFs, TGFs, TNFs and secreted forms of the beta-amyloid precursor protein. Animal and cell culture studies have shown that NPFs can attenuate neuronal injury initiated by insults believed to be relevant to the pathophysiology of traumatic brain injury (TBI) including excitotoxins, ischemia, and free radicals. Studies of the mechanism of action of these NPFs indicate that they enhance cellular systems involved in maintenance of Ca2+ homeostasis and free radical metabolism. Recent work has identified several low-molecular-weight lipophilic compounds that appear to mimic the action of NPFs by activating signal transduction cascades involving tyrosine phosphorylation. Such compounds, alone or in combination with antioxidants and calcium-stabilizing agents, have proved beneficial in animal studies of ischemic brain injury and provide opportunities for development of preventative/therapeutic approaches for TBI. PMID- 8201626 TI - In vitro investigations of the effects of nonfreezing low temperatures on lesioned and uninjured mammalian spinal neurons. AB - This two-part investigation explored the parameters and mechanisms of: (1) injury to spinal cord (SC) neurons by nonfreezing low temperatures, and (2) hypothermic protection of SC neurons subjected to a defined, physical injury (dendrite transection). Conclusions from the studies of hypothermic injury were: (1) morphologic and ultrastructural signs of stress developed in SC neurons as the temperature was decreased below 17 degrees C; (2) most neurons showing stress during cooling died upon rewarming to 37 degrees C; (3) spontaneous SC network activity was not significantly changed by cooling to 17 degrees C for 2 hours and rewarming, but cooling to 10 degrees C for 1 hour caused a reduction of burst frequency after rewarming, and cooling to 10 degrees C for 2 hours resulted in electrical silence after rewarming; and (4) application of N-methyl-D-aspartate (NMDA) antagonists before cooling prevented neuronal death, ultrastructural damage, and loss of activity upon rewarming, but application after cooling (before rewarming) was not protective. Conclusions from the studies of hypothermic protection were: (1) cooling at 17 degrees C for 2 hours followed by rewarming to 37 degrees C significantly increased lesioned neuron survival, but protection was lost when the period at 17 degrees C was increased to 6 hours; (2) NMDA blockade under normothermic (37 degrees C) or hypothermic (17 degrees C or 10 degrees C for 2 hours) conditions was not more protective of lesioned neurons than cooling to 17 degrees C (no NMDA antagonist); and (3) 200 microM thiopental or 100 microM pentobarbital increased lesioned neuron survival to a degree comparable to cooling for 2 hours at 17 degrees C. PMID- 8201627 TI - Calcitonin gene-related peptide (CGRP)-like immunoreactivity in motoneurons of the human spinal cord following injury. AB - Changes that occur in the localization of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) in motoneurons, following injury to the human spinal cord, were examined. CGRP-LI above and below the level of injury was compared to normal human spinal cord. Vibratome sections were cut and processed for immunostaining using the avidin-biotin immunoperoxidase method. Whereas motoneurons above the lesion contained CGRP-LI, below the lesion the CGRP-LI was reduced. In 3 spinal cords from patients who had survived between 1 and 8 years after injury, CGRP-LI in motoneurons of lumbar spinal cord was absent or considerably diminished. In the spinal cord from one patient who had died several years after injury, there was a unilateral augmentation of CGRP immunostaining. The results suggest that CGRP levels in motoneurons are affected by spinal cord injury in humans and that CGRP levels in motoneurons may be regulated either by supraspinal afferent inputs or by muscle activity. PMID- 8201628 TI - (S)-emopamil attenuates acute reduction in regional cerebral blood flow following experimental brain injury. AB - We examined the effects of (S)-emopamil, a phenylalkylamine calcium channel blocker with serotonin receptor antagonist properties, on regional cerebral blood flow (rCBF) following experimental brain injury in the rat. Animals were subjected to fluid percussion brain injury of moderate severity (2.1 atm), and received (S)-emopamil (20 mg/kg, i.p., n = 10) or saline (n = 10) at 20 minutes postinjury and 2.5 hours after the first injection of the drug. Consecutive rCBF measurements were performed: (1) prior to injury, (2) 15 minutes, (3) 90 minutes, and (4) 4 hours postinjury, using the radiolabeled microsphere technique. Brain injury produced an acute and significant reduction of rCBF at 15 minutes postinjury in all the regions examined (p < 0.05). At 90 minutes postinjury, rCBF remained significantly depressed in the forebrain regions. All brain regions showed a recovery of rCBF to normal by 4 hours following injury in saline-treated animals, with the exception of injured left parietal cortex and bilateral hippocampi, where rCBF remained significantly depressed. A significant attenuation of the trauma-induced reduction in rCBF was observed at 70 minutes after the first administration of (S)-emopamil in the forebrain regions and cerebellum (p < 0.05). Following the second (S)-emopamil injection, the significant improvement in rCBF observed in left injured cortex was maintained. These results suggest that (S)-emopamil may be efficacious in reversing post traumatic alterations in rCBF, which may contribute to the post-traumatic pathophysiologic sequelae. PMID- 8201629 TI - Can induced moods trigger drug-related responses in opiate abuse patients? AB - This study investigated the ability of four hypnotically induced mood states (euphoria, depression, anxiety, and anger) to trigger craving and other drug related conditioned responses in detoxified opiate abuse patients. Hypnotically induced depression produced significant increases in drug craving for opiates. Depression also tended to increase global self-ratings of opiate withdrawal. Other trends included increases in self-rated craving by induced anxiety and increases in withdrawal symptoms by induced anger. These results suggest that negative mood states, perhaps in the context of repeated attempts at self medication, may become conditioned stimuli capable of triggering craving and other drug-related conditioned responses. The ability of depression to produce reliable effects in this particular patient group may reflect the high lifetime prevalence of depression diagnoses for this sample. The implications of these findings for therapeutic strategies are discussed. PMID- 8201630 TI - Relationship between time spent in treatment and client outcomes from therapeutic communities. AB - Research found that therapeutic communities and other types of residential programs are effective in reducing drug use, unemployment, and criminal behavior and that length of time spent in treatment is an important predictor of client outcomes from programs. Studies vary considerably, however, in terms of the amount of time they found clients need to stay in treatment to produce those outcomes. Data collected for the Treatment Outcome Prospective Study (TOPS) were analyzed to explore the relationship between time spent in treatment and client outcomes from therapeutic communities and other types of residential drug treatment programs. The analysis took into account client characteristics and whether clients received drug treatment during the follow-up year. The results indicate there is a stronger relationship between time spent in treatment and client outcomes from therapeutic communities than was suggested in earlier analysis of TOPS data. PMID- 8201631 TI - The 1993 distinguished lecturer in substance abuse. PMID- 8201632 TI - A case-specific approach to the treatment of alcoholism: the application of control mastery theory to alcoholics anonymous and professional practice. AB - Effective treatment of alcoholism requires adopting a psychodynamically informed case-specific approach. Control mastery theory provides a powerful way to understand and treat the alcoholic patient. The theory posits that individuals hold unconscious pathogenic beliefs that contribute to the development and maintenance of alcoholism. The primary therapeutic goal is to create a safe atmosphere that enables patients to disabuse themselves of their maladaptive beliefs and their attendant guilt. In this way, patients become freer to more accurately test reality and thus more effectively pursue normal developmental goals. The treatment of the alcoholic patient progresses through phases, each of which poses different therapeutic challenges. The salient therapeutic tasks addressed in this article are denial, containing affect, relapse prevention, and Alcoholics Anonymous involvement. By understanding the individual's unique pathogenic belief system, the therapist is better equipped to help the patient through the generic phases and tasks of the recovery process. PMID- 8201633 TI - Anorexia nervosa: "thirty something". AB - In this report, three cases of eating-disordered women in their thirties are presented to document the occurrence of eating disorders in this age group. The clinical characteristics and associated features are described. Clinicians are reminded to consider the possibility of an eating disorder in patients who present with weight loss regardless of their age. PMID- 8201634 TI - A description of the Maternal Addiction Program of the University of Miami/Jackson Memorial Medical Center. AB - The MAP of the University of Miami/Jackson Memorial Medical Center/Highland Park Pavilion is a comprehensive inpatient and outpatient chemical dependency rehabilitation program that serves mostly lower socioeconomic, African-American perinatal substance-abusing women. The multidisciplinary treatment team incorporates a broad spectrum of group and individual therapeutic modalities, including 12-step, psychoeducational, and RP components. Within MAP programs, significant attention is given to issues and experiences that are unique to this population and that must be addressed if rehabilitation is to be successful. These topics include, but are not limited to, physical, emotional and sexual abuse, empowerment, family and parenting concerns, and HIV prevention and coping skills for HIV-seropositive women. PMID- 8201635 TI - Models for treating tuberculosis in narcotic-addicted patients. PMID- 8201636 TI - Dealing with violent behavior among AIDS patients. PMID- 8201637 TI - An open trial of low dose buprenorphine in treating methadone withdrawal. AB - Buprenorphine (BPN) is a prescription analgesic with mixed opioid agonist and antagonist properties. This pilot study conducted detailed case studies with 15 methadone dependent patients. The study sought to determine whether repeated low doses (0.15 to 0.3 mg) of sublingual BPN would relieve opioid withdrawal symptoms. Subjects developed mild to moderate withdrawal symptoms within 26 to 31 hours of methadone discontinuation. Once in withdrawal, the subjects received 0.15 mg of BPN sublingually. A second dose of 0.15 mg was administered in an hour, and a 0.30 mg dose in 2 hours, if the subject obtained no relief of withdrawal symptoms. In 6 subjects a low dose of 0.15 to 0.30 mg sublingual BPN resulted in the disappearance of subjective and objective withdrawal symptoms within 10 minutes to 2.5 hours. Four others had brief, partial relief of symptoms. Five subjects failed to experience any relief of withdrawal symptoms after a total of 0.6 mg BPN administered over 3 hours. One nonresponder suffered what appeared to be a severe precipitated withdrawal reaction similar to that which can be produced in addicts by a naloxone challenge. The 4 Caucasian responders required 1 to 2 hours to respond to BPN, whereas the 2 African American responders required only 10 to 20 minutes. Low (analgesic) doses of BPN were sufficient to treat all methadone withdrawal symptoms in 6 of 15 subjects. There may be ethnic differences in response to BPN. Low dose BPN may play a role in carefully monitored heroin detoxification treatment. PMID- 8201638 TI - Urinary incontinence. PMID- 8201639 TI - Increased serum levels of anti-elastin antibodies in patients with Peyronie's disease. AB - The cause of Peyronie's disease is unknown. Immunological mechanisms in the pathogenesis have been previously suggested. Antibodies to elastin are present in all individuals. However, abnormal serum levels of anti-tropoelastin (reflecting elastin synthesis) and anti-alpha-elastin (reflecting elastin destruction) are seen in a variety of autoimmune diseases. We show that patients with Peyronie's disease have higher levels of antibodies to tropoelastin (p < 0.047) and alpha elastin (p < 0.012) than age-matched controls, suggesting an increase in elastin synthesis and breakdown, respectively. These findings suggest the presence of autoimmune mechanisms in the pathogenesis of Peyronie's disease, which may have future diagnostic and therapeutic implications. PMID- 8201640 TI - Relationship of sperm parameters with levels of reactive oxygen species in semen specimens. AB - The levels of reactive oxygen species were compared in semen specimens from suspected subfertile men and from normal volunteers, and correlated with other semen parameters. Reactive oxygen species formation was measured in semen samples that had no white blood cells by a chemiluminescence assay with a Luminometer. The relationship of seminal reactive oxygen species to several sperm parameters was evaluated. A total of 84 specimens from 69 suspected subfertile men and 15 normal volunteers was tested for reactive oxygen species production. Comparison of reactive oxygen species levels in white blood cell-negative patient and donor specimens showed significantly higher values (p < 0.005) in the patient group. Similarly, levels in patient and donor specimens with normal sperm motility were significantly lower (p < 0.005) than those in specimens showing poor motility. The seminal reactive oxygen species levels of white blood cell-negative patients with abnormal morphology were significantly higher (p < 0.005) than those in white blood cell-negative patients with normal morphology. Our results show that seminal reactive oxygen species levels in suspected subfertile men are significantly higher than in normal men, and that the presence of excess reactive oxygen species in semen is positively correlated with low sperm concentration, poor motility and poor morphology. In conclusion, the evaluation of reactive oxygen species levels in cases of idiopathic male infertility could serve as an important marker of sperm dysfunction. PMID- 8201641 TI - Touch preparation cytological evaluation of radical prostatectomy specimens. AB - The failure of current histological techniques to predict local failure and disease progression after radical prostatectomy is supported by substantial evidence. Moreover, the characterization of histological findings is hampered by the lack of uniform interpretation. We report a prospective study of 92 patients undergoing radical prostatectomy for clinical stages A and B prostate cancer in which the technique of touch preparation cytological analysis of surgical margins is compared to the standard histological approach. We evaluated 47 pathological stage B, 43 stage C and 2 stage D specimens. Specimens initially assigned to pathological stage B were upstaged to stage C on review by 1 blinded pathologist in 19 of 65 cases (29%). Overall, 15 of 47 histological stage B specimens (32%), 20 of 43 histological stage C specimens (47%) and 2 of 2 histological stage D specimens (100%) had malignant cells identified on the margins by touch preparation cytology. Postoperative mean followup of 7 months (range 0.4 to 26) revealed that 7 of 14 nonstage D cancer patients (50%) with elevated serum prostate specific antigen levels had positive cytology results, including 1 with histologically confirmed organ-confined disease. Among the stage C specimens cytology was more likely to be positive if there was concomitant seminal vesicle invasion. Correlation of this information with eventual patient course during the long term will be necessary to assess its role in patient management. PMID- 8201642 TI - A prospective comparison of treatments for symptomatic hot flushes following endocrine therapy for carcinoma of the prostate. AB - In a prospective, comparative study 68 men were treated for hot flushes after androgen deprivation therapy for prostate cancer. Complete responses (elimination of hot flushes) were rare in patients receiving either combined phenobarbital plus ergotamine or clonidine. Of the men receiving either diethylstilbestrol or megestrol acetate 70% had a complete response, while another 20% had a greater than 50% decrease in the severity of hot flushes. Based upon a lower incidence of side effects, oral megestrol acetate was the preferred treatment for hot flushes in this study. PMID- 8201644 TI - Transverse "S" laparotomy for radical nephrectomy and upper retroperitoneal access. AB - A modified transverse laparotomy is described that allows for safe removal of bulky kidney or adrenal tumors and suprarenal hilar lesions in cases of metastatic testicular cancer. The full exposure of the upper retroperitoneal area provided by this access obviates the need for a thoracoabdominal incision with its attendant drawbacks. Our experience with the transverse S laparotomy in more than 80 patients with large renal or retroperitoneal tumors confirmed the wide local exposure obtained, short hospital stay and absence of pulmonary complications that can occur after the thoracoabdominal approach. PMID- 8201643 TI - Effective postcoital quinolone prophylaxis of recurrent urinary tract infections in women. AB - A total of 33 sexually active, premenopausal and postmenopausal women, suffering from recurrent urinary tract infections was randomized to receive postcoital prophylaxis with a dose of either 100 mg. ofloxacin (12), 200 mg. norfloxacin (11) or 125 mg. ciprofloxacin (10). While 130 urinary tract infections occurred in these patients during a mean of 8 months before postcoital quinolone prophylaxis, only 1 occurred during a mean of 15 months following prophylaxis. This difference was statistically highly significant. Each of these patients ingested a mean of 117 quinolone doses per year of postcoital prophylaxis. Before prophylaxis 74% of the introital cultures yielded gram-negative enterobacteria (mainly Escherichia coli), whereas only 11% yielded the same bacteria following prophylaxis. Postcoital oral prophylaxis with minimal quinolone doses is highly effective in the prevention of recurrent urinary tract infections in women, because it achieves high urinary bactericidal concentrations, and clears the majority of the introital and urethral Enterobacteriaceae without inducing resistance to the quinolones despite long-term treatment. This prophylaxis is highly recommended because of its ease of compliance, preservation of drug efficacy, lack of toxicity and cost-effectiveness. Postcoital quinolone prophylaxis is as good as or better than daily quinolone prophylaxis and uses only a third of the amount of drug consumed in daily prophylaxis. PMID- 8201645 TI - Facilitated implantation of the inguinal reservoir of the multicomponent inflatable penile prosthesis. AB - We present a method of implantation of the inguinal reservoir of the multicomponent inflatable penile prosthesis that permits safe 1-step creation of an adequate prevesical space. The preperitoneal distention balloon is inflated in the prevesical space to produce a compartment of adequate volume to avoid back pressure on the reservoir and minimize potential bladder injury in the setting of previous pelvic surgery. PMID- 8201646 TI - Relationship between bladder neck diameter and hydraulic energy at maximum flow. AB - A pressure-flow study was performed with a 5-micro-tip transducer catheter in 6 normal male volunteers (bladder neck diameters 0.80 cm. or larger) and 13 male subjects suspected of having bladder neck contracture. Intraurethral pressure was measured at various sites in the urethra at maximum flow to calculate hydraulic energy at these sites using the Bernoulli equation. When the subjects were divided into 2 groups (1 group with a bladder neck diameter of 0.73 cm. or larger and 1 with a bladder neck diameter of 0.60 cm. or smaller), the relative value of energy (ratios to the initial energy generated in the bladder) at the external urethral sphincter was significantly (p < 0.01) greater in the former than in the latter group. Therefore, the "flow rate controlling zone" lies at the external urethral sphincter in the former group and at the bladder neck in the latter group. PMID- 8201647 TI - Preoperative external beam radiotherapy followed by cytoreductive surgery and intraoperative radiotherapy for locally advanced primary or recurrent renal malignancies. AB - Patients with local persistence or local regional recurrence of cancer after nephrectomy for renal cell cancer are unlikely to respond well to systemic therapy or external irradiation alone. In this analysis, patients with locally recurrent (9) or persistent (2) cancer following nephrectomy (renal cell cancer in 8, transitional cell or squamous cell cancer in 3) usually received 4,500 to 5,040 cGy. preoperative external beam irradiation followed by maximal surgical debulking and intraoperative electron irradiation (1,000 to 2,500 cGy.). Of 8 renal cell cancer patients 6 were alive and 4 were without disease progression at 15 to 50 months (3 of 4 at 29 months or longer). One patient died free of disease at 10.5 months and 3 had metastases (regional in 1 and distant in 3). Of the 3 transitional or squamous cell carcinoma patients 1 died free of disease 28.5 months after initiation of treatment for recurrence and 2 died of disease progression (liver in 1 and local in 1). It appears that select patients with solitary local recurrence or persistence following radical nephrectomy for renal cell cancer may benefit from an aggressive local treatment approach using irradiation (preoperatively and intraoperatively) plus maximal surgical debulking. In patients with locally advanced high grade transitional cell cancer the locally aggressive approach should probably be combined with multi-drug chemotherapy because of increased systemic risks. For both groups (renal cell carcinoma and transitional/squamous cell carcinoma) the most ideal patient for such treatment is one who has not received prior chemotherapy or external irradiation to the site of relapse, since 3 of 5 patients with disease progression after our aggressive approach had received chemotherapy (2) or external beam irradiation (2) elsewhere before referral. PMID- 8201648 TI - Atypical appearance of adrenal pseudocysts. AB - We report 2 cases of adrenal pseudocysts that resulted from hemorrhage into a normal adrenal gland and that showed atypical imaging features on computerized tomography and ultrasonography. The presence of a solid component within the mass and/or central calcification, which is unlike the typical features of adrenal pseudocyst, suggested a diagnosis of adrenal tumor. The solid component diminished on computerized tomography in 26 days in case 1 and in 16 days in case 2, which seemed to represent resolving hematoma. The atypical appearance of these adrenal pseudocysts, especially the changeable pattern of the solid component within the mass, should be kept in mind to ensure a correct preoperative diagnosis. PMID- 8201649 TI - Leiomyosarcoma of the renal vein: a case report. PMID- 8201650 TI - Spontaneous remission of renal cell carcinoma: a case report and immunological correlates. AB - Spontaneous remission of renal cell carcinoma is a rare occurrence for which immunological factors have been implicated as a possible mechanism. We report a case of spontaneous remission of metastatic renal cell carcinoma in which we assayed various immune parameters. At remission we found no enhancement of natural killer cell, lymphokine-activated killer cell or lymphocyte proliferative response. PMID- 8201651 TI - The ovarian remnant syndrome and ureteral obstruction: medical management. AB - The ovarian remnant syndrome represents the development of symptoms due to residual ovarian tissue after bilateral salpingo-oophorectomy. Treatment generally consists of surgical resection but recurrence after resection is common. A case is reported in which a postoperative recurrent ovarian remnant was successfully managed by using a luteinizing hormone-releasing hormone agonist. In addition, this report includes a survey of gynecologists to determine the frequency of this syndrome and of ureteral involvement. PMID- 8201652 TI - A case of familial central diabetes insipidus: the response of urinary prostaglandins to 1-deamino-8-D-arginine vasopressin. AB - A case of familial central diabetes insipidus and dilatation of the urinary tract is reported. Administration of desmopressin for 1 year improved urinary tract dilatation with a concomitant reduction in urine volume. Urinary cyclic adenosine monophosphate and prostaglandin E2 excretion increased after treatment. PMID- 8201653 TI - Urinary retention with glans hypervascularization after penile arterialization. AB - Penile revascularization is a relatively new treatment for impotence. Glanular hypervascularization is a known complication of a venous arterialization procedure and it requires surgery for cure. A case in which delayed glanular hypervascularization caused urinary retention is presented. Ligation of the distal deep dorsal vein via the retro-coronal plexus resulted in cure. PMID- 8201654 TI - Ruptured testicular prosthesis. PMID- 8201655 TI - The decline of urological education in United States medical schools. AB - In 1956, 99% of all medical schools required a clinical rotation through urology during year 3 or 4. By 1978 this percentage had decreased to 48% and currently it is only 38%. In addition, an estimated 10 to 15% of medical school graduates have never been exposed to urology (no lectures and no clinical rotation). Urological diseases continue to comprise a significant percentage of problems encountered by primary care physicians. The Education Council of the American Urological Association has adopted urological education objectives that should be incorporated into the curriculum of every medical school. PMID- 8201656 TI - Re: Ascorbate acid overdosing: a risk factor for calcium oxalate nephrolithiasis. PMID- 8201657 TI - Re: Comparison of RigiScan and formal nocturnal penile tumescence testing in the evaluation of erectile rigidity. PMID- 8201658 TI - Re: Testicular torsion: pitfalls of color Doppler sonography. PMID- 8201659 TI - Re: Oral immunotherapy of recurrent urinary tract infections: a double-blind placebo-controlled multicenter study. PMID- 8201660 TI - Prenatal findings associated with a unilateral nonfunctioning or absent kidney. AB - Prenatal findings in infants who were postnatally found to have a unilaterally nonfunctioning cystic, dysplastic or absent kidney were evaluated to understand better the prenatal pathophysiology of these conditions. Of the 38 cases in which prenatal and postnatal renal imaging studies were done fetal renal conditions leading to postnatal dysplasia or absence included small echogenic kidneys in 3, typical multicystic dysplasia in 30, obstructive uropathy in 4 and perinephric urinoma in 1. Abnormalities were noted on postnatal imaging in 30% of the contralateral kidneys. Vesicoureteral reflux was the most commonly identified abnormality, occurring in 23% of the cases. PMID- 8201661 TI - Unsuspected ureterocele and ureteral duplication. AB - Four patients presenting with high grade unilateral vesicoureteral reflux were discovered at surgery to have an unsuspected duplex system with a ureterocele associated with the upper pole of the refluxing kidney. No preoperative radiographic study was diagnostic for duplication or ureterocele but when studies were reviewed retrospectively subtle evidence suggesting this possibility could be identified in a few cases. This rare situation should be considered whenever massive unilateral vesicoureteral reflux is encountered. PMID- 8201662 TI - The unsuspected cecoureterocele. AB - A review of 54 consecutive cases of ectopic ureterocele treated at our institution in the last 15 years revealed 4 cases of the cecoureterocele variant. Although the diagnosis of ectopic ureterocele was made preoperatively, the more accurate diagnosis of cecoureterocele was not suggested by preoperative radiographic studies. The cecocele component was disclosed only at endoscopy or during open resection of the ureterocele. A review of the presentation, preoperative assessment, intraoperative management and outcome of each case of unsuspected cecoureterocele suggests that optimal surgical management of the cecocele itself does not require total removal. PMID- 8201663 TI - Long-term intermittent catheterization: the experience of teenagers and young adults with myelomeningocele. AB - An interview study of the practical aspects of clean intermittent self catheterization was performed in 26 randomly chosen teenagers and young adults with myelomeningocele who had been using the procedure for 7.5 to 12 years. Self catheterization was well accepted as a part of daily life. Even if complete dryness was not attained the subjects appreciated the smaller pads and the decrease in leakage, which was a source of embarrassment. No one in the study group wanted to return to the previous voiding technique. Careful introduction, continuous support and consistent encouragement were important factors in obtaining these favorable results. PMID- 8201664 TI - Vaginal reconstruction: critical technical principles. AB - Childhood vaginal anomalies are frequently encountered, often in association with significant anorectal or urinary tract abnormalities. As a result, reconstruction poses a number of technical challenges. We maintain that the best results are achieved by single stage perineal reconstruction. The primary goal of achieving a functional and cosmetically adequate vagina must not be at the expense of the optimal repair of associated urinary and anorectal abnormalities. In addition, since these repairs are performed early in childhood, vaginal growth is an issue that further limits the choice of reconstructive technique. We present a series of successful vaginal reconstructions in complex cases and an outline of the principles of surgical care. PMID- 8201665 TI - Surgical implications of genitourinary tract anomalies in patients with imperforate anus. AB - Genitourinary anomalies in patients with imperforate anus are a frequent source of significant morbidity. We report a retrospective study of 64 genitourinary procedures performed on 23 patients. Renal, collecting system, bladder and perineal anomalies were encountered in 65%, 83%, 87% and 65% of these complex cases, respectively. A total of 70% of the patients required intermittent catheterization due to bladder dysfunction. Surgical alternatives, complications of management and functional outcomes are reviewed in detail. Genitourinary reconstruction is best undertaken as an integral part of imperforate anus reconstruction. Failure to do so results in the loss of surgical alternatives, unnecessary reoperative procedures and compromised outcomes. PMID- 8201666 TI - This month in Investigative Urology. Commentary on development of a mouse model for nonbacterial prostatitis. PMID- 8201667 TI - Long-term studies of urease-induced crystallization in human urine. AB - Urine samples were inoculated with viable Proteus mirabilis or purified Jack bean urease. The subsequent pH increase and crystallization were followed for 2 weeks. Particle formation was detected much earlier and at a lower pH in urines inoculated with Proteus, in which a higher end pH was also reached. The crystal configuration in bacteria and urease inoculated samples was different. Crystal aggregation was also much more pronounced in the Proteus mirabilis inoculated samples. The total precipitation was markedly increased in the Proteus mirabilis inoculated samples. The presence of live Proteus mirabilis thus has a profound influence on urease-induced crystallization in human urine. Despite the formation of rather large crystal aggregates in the Proteus-inoculated urines, no firm aggregates of a "prestone" type were observed. PMID- 8201668 TI - Protamine sulfate and vancomycin are synergistic against Staphylococcus epidermidis prosthesis infection in vivo. AB - We have previously demonstrated that the quaternary amine, protamine sulfate (PS), is bactericidal against Staphylococcus epidermidis. In an attempt to decrease genitourinary prosthesis infection rates, we examined the ability of PS as a wound irrigant to inhibit Staphylococcus epidermidis viability. Eighty-seven Sprague-Dawley rats were studied by implanting a sterile silicone pellet in their dorsum. The pellet was inoculated with Staphylococcus epidermidis and the rats were divided into four groups based on the wound irrigant employed after inoculation: (1) control (sterile water) (2) vancomycin; (3) PS; (4) vancomycin + PS. All rats received perioperative and daily intramuscular vancomycin, and the pellets were explanted on postoperative day 28 and cultured. The infection rates were: (1) control 77%, (2) vancomycin 50%, (3) protamine sulfate 67%, and (4) protamine sulfate and vancomycin 19%. The differences between (2) vancomycin versus (4) vancomycin + PS and (3) PS versus (4) vancomycin + PS were significant (p = 0.05 and p < 0.005). The data suggest that PS potentiates vancomycin as a wound irrigant in prosthesis implantation. PMID- 8201669 TI - Enhanced cytologic detection of early stage mouse bladder tumor following induction of uroepithelial cell shedding. AB - Previous studies from our laboratory have shown that some Escherichia coli endotoxins are capable of inducing massive normal urothelial cell shedding. In the present study we investigated whether endotoxin-induced shedding improves cytologic detection of early stage mouse bladder cancer. Mouse bladder tumor (MBT 2) cells were implanted intravesically in the submucosa of C3H female mice. Ten to 21 days later the bladders were irrigated with saline followed by instillation of endotoxin. The bladder contents of each mouse were aspirated and examined cytologically together with the bladder wash specimen. Shedding of epithelial cells was observed in only 32% of the saline irrigated specimens compared with 93% after endotoxin instillation (p < 0.00001). Analysis showed an overall accuracy rate of 39% after saline barbotage versus 78% following endotoxin administration (p < 0.00001). These results indicate that intravesical instillation of specific bacterial endotoxin significantly increases the extent of cytologic detection of early stage superficial bladder cancer. PMID- 8201670 TI - Management of combined renal and pancreatic trauma. AB - During a 15-year period we treated 38 patients with combined renal and pancreatic injuries (40 kidneys): 18 patients (19 kidneys) with renal contusion (89% from blunt trauma) and 20 with renal laceration or vascular injuries (90% from penetrating trauma). All patients with renal contusion were managed conservatively without complication, despite major pancreatic injury in a third. The 16 patients with significant renal and pancreatic injuries were classified as a high risk group: 3 underwent nephrectomy for vascular injuries that could not be repaired but all of the remaining kidneys were salvaged. Perinephric abscesses developed in 2 of these patients, for a major complication rate of 15%. No secondary nephrectomies were necessary, nor did urinary fistulas develop. We conclude that significant renal injuries in patients with major pancreatic injuries may be managed by renal repair with an increased but acceptable complication rate and that nephrectomy should be performed only if the degree of renal injury precludes repair. PMID- 8201671 TI - Renal hemodynamic and functional effects of 10 days' partial urinary obstruction in the fetal lamb. AB - We studied fetal lambs to define the renal pathophysiology of chronic in utero partial bladder outlet obstruction. These fetal lambs, 115 to 120 days gestation (term = 145 days), underwent urethral ligation, placement of a urachal catheter and positioning of an ultrasonic flow transducer around the left renal artery. Partial obstruction was created by placing a narrow connector between the urachal and an amniotic catheter. In control animals a large connector was placed to allow free drainage of the bladder into the amniotic cavity. Renal blood flow was measured daily, and urine was collected at days 5 and 10 to evaluate renal function. In control animals, no significant changes in any parameters were observed. In the partially obstructed fetal lambs, renal blood flow increased to 165% of baseline after 5 days; from 5 to 10 days, it decreased, but remained above baseline values through 10 days (128%). Urine production dropped significantly after 10 days (67%). Glomerular filtration rate increased slightly after 5 days (127%), but decreased after 10 (56%). Filtration fraction steadily decreased after 5 (70%) and 10 days (33%). Fractional and total sodium excretion did not change. Renal blood flow increases, filtration fraction decreases and renal function trends progressively diminish in response to partial bladder outlet obstruction over a period of 10 days in the fetal lamb. PMID- 8201673 TI - Colonization of urinary catheters by Escherichia coli and Providencia stuartii in a laboratory model system. AB - A laboratory model system was developed to investigate the progressive colonization of urinary catheters by Escherichia coli Providencia stuartii, prominent organisms in the polymicrobial bacteriuria of the long-term catheterized urinary tract. We hypothesized that colonization of the catheter and artificial urine by E. coli is influenced by the presence of P. stuartii. E. coli or P. stuartii in pure culture both rapidly colonized the artificial urine and catheters, and both persisted throughout all experiments. In systems containing both organisms, P. stuartii occurred in significantly higher numbers in the artificial urine and on the catheters than E. coli (p < 0.05). To obtain similar numbers of E. coli and P. stuartii in the artificial urine, citrate was eliminated; however, P. stuartii still dominated on the catheter surfaces. The presence of P. stuartii appeared to facilitate growth of E. coli in the artificial urine, yet reduce numbers of E. coli on the catheter. In a separate experiment using different strains of E. coli and P. stuartii, the latter was dominant in the artificial urine and on the catheter surfaces. However, this strain of P. stuartii (which was urease positive) did not facilitate growth of E. coli. The interaction between these strains may have been considerably affected by urea hydrolysis, which resulted in an increase in pH (6.5 to > 8.5) and considerable precipitate formation in the model system. The paradox of P. stuartii enhancing colonization by E. coli in the artificial urine, yet inhibiting its colonization on the catheter surface, illustrates the complexity of polymicrobial interactions in colonization of the catheterized urinary tract. PMID- 8201672 TI - Distinct androgen 5 alpha-reduction pathways in cultured fibroblasts and immortalized epithelial cells from normal human adult prostate. AB - All androgen-sensitive peripheral tissues and cells, including the prostate, are commonly believed to possess the ability to metabolize testosterone. We report on the in vitro metabolism of tritiated testosterone performed in immortalized human adult normal prostatic epithelial cells and in human adult normal prostate fibroblastic cells (stromal cells). These two cell types were incubated separately with increasing testosterone concentrations (1 to 50 nM.) for 2 and 4 hours, after which the testosterone metabolic profile was analyzed. Data analysis provided evidence, for the first time, of the existence of two different 5 alpha reduced metabolic pathways. Stromal cells preferred the androsterone pathway via the oxidative androstenedione formation, whereas epithelial cells preferred the reductive 5 alpha-dihydrotestosterone pathway. These two 5 alpha-reduced metabolites were produced in nearly equal quantities regardless of testosterone concentration or time of incubation. Since interactions between epithelial and stromal cells are involved in the development of the prostate, the availability of defined epithelial and stromal cells suitable for in vitro experiments provides a useful tool for the study of the contribution of androgens to these interactions. The model presented in this study would permit a better evaluation of the intraprostatic regulation of androgen metabolism and the contribution of the anti-5-alpha-reductase drugs to the management of benign prostate hyperplasia. PMID- 8201674 TI - Oxalate transport in a line of porcine renal epithelial cells--LLC-PK1 cells. AB - The present studies examined oxalate handling in LLC-PK1 cells, an epithelial cell line of porcine origin. These cells appear to express transport systems for oxalate, as evidenced by the fact that uptake was saturable, time dependent and sensitive to the anion transport inhibitor DIDS (4,4'-diisothiocyanostilbene-2,2' disulfonic acid). Oxalate uptake in these cells was also affected by the presence of certain inorganic anions (Cl-, SO4(2-), or HCO3-) but not by organic anions (para-aminohippurate, urate, malate, phenylsuccinate, succinate). This uptake was Na independent and unaffected by changes in membrane potential but was affected by external pH, with acidic pH stimulating and alkaline pH inhibiting oxalate accumulation. These findings suggest that LLC-PK1 cells express oxalate transporters similar to those observed in the mammalian renal cortex. Further studies using these cells may prove useful in defining the conditions that govern transcellular oxalate flux in renal epithelial cells. PMID- 8201675 TI - Tumor associated glycoprotein-72 is highly expressed in prostatic adenocarcinomas. AB - We examined the expression of two well-characterized oncofetal antigens, the tumor associated glycoprotein-72 (TAG-72) and carcinoembryonic antigen (CEA), in malignant prostatic tissues. Three specific monoclonal antibodies, B72.3, CC49 and CC83, were used to examine the expression of TAG-72. Immunoreactivity was detected in 63% of the malignant specimens using B72.3. CC49 and CC83 were more sensitive than B72.3 in detecting TAG-72 expression. Immunoreactivity was detected in approximately 80% of prostatic adenocarcinomas with CC49 or CC83. The pattern and localization of TAG-72 immunoreactivity were similar for the three antibodies with most immunoreactivity observed within the cytoplasm of malignant cells and within the lumens of malignant glands. TAG-72 immunoreactivity was not detected within benign epithelium or stroma, with the exception of focal epithelial expression in areas of acute prostatitis. The COL-1 antibody to CEA did not detect CEA in benign glands, stroma, or malignant cells of prostate specimens resected for prostatic adenocarcinoma. These results demonstrate that TAG-72, but not CEA, is frequently expressed in prostatic adenocarcinomas. PMID- 8201676 TI - Development of a mouse model for nonbacterial prostatitis. AB - Nonbacterial prostatitis is a common clinical entity which is often difficult to diagnose and treat. Little is known with regard to the etiology and pathogenesis of this disease process. To develop an animal model and characterize the immune parameters of nonbacterial prostatitis, we harvested the prostates from SJL, AJ, Balb/c, C57bl/6 and C57bl/6 lpr mice. These prostates were homogenized and injected into syngeneic mice. Controls were injected with Freund's complete adjuvant only. Mice from each group were sacrificed 30 days after injection, and the prostates were harvested. Prostatic tissue was examined histologically for degree of inflammation. None of the Balb/c mice exhibited prostatic inflammation. The SJL and AJ mice exhibited varying degrees of prostatic inflammation. All of the C57bl/6 mice were found to have lymphocytic infiltration of the stroma and periglandular region. The C57bl/6 lpr mice did not appear to be more susceptible than the parental strain. Adoptive transfer studies demonstrated the prostatic inflammation to be at least in part immune mediated. We conclude that injection of syngenic prostate antigen induces prostatic inflammation similar to clinical nonbacterial prostatitis. Nonbacterial prostatitis may be an autoimmune process. PMID- 8201677 TI - Results of conservative management of clinically localized prostate cancer. PMID- 8201678 TI - The role of C-reactive protein and erythrocyte sedimentation rate in the diagnosis of infected hydronephrosis and pyonephrosis. AB - Serum C-reactive protein levels and erythrocyte sedimentation rates were prospectively evaluated in 38 patients with dilated pyelocaliceal systems in an attempt to distinguish simple hydronephrosis from infected hydronephrosis and pyonephrosis. The clinical presentations of infected hydronephrosis and pyonephrosis were extremely variable, ranging from no constitutional complaints to urosepsis. Renal sonography detected only 6 of 16 patients with pyonephrosis (specificity 96%, sensitivity 38%, accuracy 72.5%). Using a cutoff value of 3.0 mg./dl. for C-reactive protein and 100 mm. per hour for erythrocyte sedimentation rate, the diagnostic accuracy of detecting infected hydronephrosis and pyonephrosis increased to 97%, with a specificity of 89% and sensitivity of 100%. Based on our experience, we believe that the serum C-reactive protein and erythrocyte sedimentation rate levels can be used as screening tests to distinguish pyonephrosis and infected hydronephrosis from simple, uncomplicated hydronephrosis. PMID- 8201679 TI - Results of the Sixth International Society of Pediatric Oncology Wilms' tumor trial and study: a risk-adapted therapeutic approach in Wilms' tumor. PMID- 8201680 TI - Nephrocalcin in patients with renal cell carcinoma. AB - Nephrocalcin, an acidic glycoprotein that inhibits calcium oxalate crystal growth, has been previously localized in proximal tubules of kidneys by an immunohistochemical staining method and purified from tissue culture media of 2 renal carcinoma cell lines. A polyclonal antibody specific to nephrocalcin was raised in rabbits and the level of nephrocalcin was quantitatively determined in urine of 19 renal cell carcinoma patients (0.241 +/- 0.341 microgram nephrocalcin per mg. creatinine) and compared to healthy controls (0.022 +/- 0.012 micrograms nephrocalcin per mg. creatinine). Nephrocalcin levels after tumor nephrectomy decreased dramatically in 5 patients and to a lesser degree in 7. A specific nephrocalcin fraction that was eluted from an anion exchange column with low ionic strength was detected in urine of the renal cell carcinoma patients, and this fraction decreased or disappeared after tumor nephrectomy in 6 of 9 patients studied. Amino acid composition, phosphate content and dissociation constants toward calcium oxalate monohydrate crystals were investigated in the nephrocalcin from tumor patients and compared to that from healthy controls. Our studies demonstrate that nephrocalcin in patients with renal cell carcinoma is atypical and usually in much higher quantity. Further studies are needed to determine the clinical significance of these observations. PMID- 8201681 TI - The evolution of renal angiomyolipomas in patients with tuberous sclerosis. AB - In 1986, 23 patients with renal angiomyolipomas as part of tuberous sclerosis were assessed by ultrasonography. In 1991, 20 patients in this group were reexamined with special attention paid to the renal pathological condition. Ultrasonography was performed by the same radiologist who performed the examination in 1986. Of 20 patients 7 had severe hemorrhage necessitating hospital admission (5 had a renal lesion larger than 3.5 cm. in diameter). In 2 patients the exact diameter of the renal angiomyolipomas could not be determined and they underwent nephrectomy. Three patients underwent successful selective embolization of the bleeding angiomyolipoma. One patient died. The hemorrhage resolved spontaneously in 1 patient and treatment was not feasible. In 4 patients the lesions increased in size between 1986 and 1991. Based on these results there is a relationship between the size of the angiomyolipomas and the risk of bleeding. Renal angiomyolipomas larger than 3.5 cm. in diameter have a substantial risk for severe hemorrhage. Some angiomyolipomas show progression. Periodic followup is mandatory every 6 months. For angiomyolipomas larger than 3.5 cm. in diameter an aggressive approach is advised. Selective embolization is the initial method of choice. PMID- 8201682 TI - Nephron sparing surgery in incidental versus suspected renal cell carcinoma. AB - From 1956 to 1992 nephron sparing surgery was performed in 216 patients with sporadic renal cell carcinoma. Renal cell carcinoma was suspected in 121 patients and was an incidental finding in 95. Compared to suspected renal cell carcinoma, incidental tumors were smaller (p = 0.0004), more often unilateral (p = 0.001) and of lower pathological stage (p = 0.001). Incidental tumors were also associated with improved 5-year cancer-specific survival (p = 0.003) and a lower rate of postoperative tumor recurrence (p = 0.001). The overall 5-year cancer specific survival rate was improved in patients with stage I versus higher stage renal cell carcinoma (p = 0.0002), unilateral versus bilateral disease (p = 0.0001), a single versus multiple tumors in the operated kidney (p = 0.01) and tumors smaller than 4 cm. versus larger tumors (p = 0.03). There were no postoperative tumor recurrences and the 5-year cancer-specific survival rate was 100% in patients with unilateral, stage I tumors smaller than 4 cm. These data define specific eligibility criteria for nephron sparing surgery in patients with localized unilateral renal cell carcinoma and a normal contralateral kidney. PMID- 8201683 TI - Micropenis: medical and surgical implications. PMID- 8201684 TI - Renal tumors. PMID- 8201685 TI - Pathological effects of extracorporeally generated shock waves on calcified aortic aneurysm tissue. AB - This study was done to define further the limits of extracorporeal shock wave lithotripsy (ESWL) in the setting of proximate calcified aneurysms. Calcified aortic aneurysmal tissue was harvested from patients undergoing elective abdominal aneurysm repair. The aneurysmal tissue was divided into control and experimental sections, and then suspended in normal saline at the F2 focal point, and at 2 and 5 cm. away from the F2 focal point in the major parallel axis of an unmodified Dornier HM3 lithotriptor. Shock waves (200, 500 or 1,000) were delivered at 18 kv. at F2, F2 plus 2 cm. and F2 plus 5 cm. The specimens were then analyzed histopathologically first to compare control and experimental sections for differences in preexisting calcification, hemorrhage and inflammation, and then to grade them for overall evidence of tissue disruption. No significant pathological difference was found between control and experimental specimens treated under these parameters. Our study suggests that human aortic aneurysmal tissue undergoes little pathological change when subjected to therapeutic range ESWL. These findings support previous clinical observations that the presence of a proximate calcified aneurysm does not necessarily preclude ESWL for the treatment of renal or ureteral calculi. The spatial and power limits used in this study may help provide a basis for future safe management of renal and ureteral calculi with ESWL in this setting. PMID- 8201686 TI - Bilateral same session ureteroscopy. AB - During a period of 4 years we performed 15 bilateral 1-session ureteroscopic examinations in 13 patients. Indications included bilateral ureteral and/or renal calculi, unexplained hydronephrosis, hematuria or filling defects, and bilateral ureteral stent placement in situations when conventional retrograde methods of stent placement failed. Balloon or hydraulic intramural ureteral dilation was performed in all cases before rigid or flexible endoscopy. There were no major short-term or long-term complications resulting from bilateral 1-session ureteroscopy. PMID- 8201687 TI - Effects of stents on lithotripsy of ureteral calculi: treatment results with 18,825 calculi using the Lithostar lithotriptor. AB - Between November 14, 1988 and August 1, 1993, 18,825 ureteral calculi were treated in the United States using 25 different mobile and 2 fixed base Siemens Lithostar lithotriptors. Lithotripsy was performed by 1,012 urologists using the modified Puigvert technique. The overall stone-free rate was 83.8% with a retreatment rate of 10.8%. The stone-free rate varied from 85.8% with stones of 10 mm. or smaller to 67.9% for stones larger than 20 mm. A ureteral stent or catheter was placed before lithotripsy in 19.3% of all treatments and 80.7% had in situ treatment without instrumentation. For calculi of any size, the use of ureteral stents or catheters had no effect on treatment outcome at any ureteral location. PMID- 8201688 TI - Quality assurance: monitoring lithotriptor output and its clinical implications. AB - Serial acoustic output measurements performed on the an electromagnetic lithotriptor consistently showed significant decreases in the output of the shock heads. A decrease in output during the lifetime of the shock head to less than 50% of its original output was observed. Decreased output was related to a higher number of shocks per treatment and a higher retreatment rate. Quality control of the lithotriptor output was reflected in better clinical results, a lower mean number of shocks per treatment, a lower retreatment rate and less time on the table, which has important clinical and financial implications. Acoustic output measurements on lithotriptors should be mandatory to achieve the best possible clinical results from extracorporeal shock wave lithotripsy. PMID- 8201689 TI - Optimal therapy for the distal ureteral stone: extracorporeal shock wave lithotripsy versus ureteroscopy. AB - Extracorporeal shock wave lithotripsy (ESWL not equal to) is the optimal therapy for renal calculi less than 2 cm. in diameter and for proximal ureteral calculi. Controversy continues over the initial approach to distal ureteral calculi (that is below the bony pelvis): in situ ESWL versus ureteroscopy. Since February 1990, 76 distal ureteral calculi were treated at our institution using either in situ ESWL (Dornier HM3 ESWL with a Stryker frame modification in 27 patients or Siemen's Lithostar electromagnetic ESWL in 22) or ureteroscopy (27 patients). Patient age and stone size were similar among the groups. All ESWL treatments were performed with the patient under intravenous sedation and on an outpatient basis. Stone-free rates were 96% for the HM3 device, 84% for the Lithostar and 100% for ureteroscopy. Retreatment was required in 3 Lithostar cases (14%) and 1 HM3 case (4%). When compared to ESWL ureteroscopy for distal ureteral stones was more time-consuming, entailed routine placement of a ureteral stent, often required general anesthesia, more often led to hospitalization and doubled the convalescence period. From a cost standpoint, ESWL on an HM3 unit was a few hundred dollars more expensive than ureteroscopy. In summary, we believe that in situ ESWL provides optimal first line therapy for distal ureteral calculi, while ureteroscopy is better reserved as a salvage procedure should ESWL fail. PMID- 8201690 TI - Technique versus technology: what is the most appropriate method for the removal of ureteral calculi. PMID- 8201691 TI - Dilation of lower ureteral strictures with Van Andel catheters. AB - We present a simple method to dilate ureteral strictures, which was performed in 7 patients with metastatic cancer (1 breast, 1 lymphoma, 2 ovarian and 3 colorectal tumors) who presented with newly discovered obstruction in the distal ureter. The obstruction was due to tumor in the pelvis in 5 patients and to pelvic radiotherapy in 2. A 0.035-inch guide wire was passed beyond the stricture cystoscopically. In each case a double pigtail stent could not be passed beyond the stricture over the guide wire. The strictures were then dilated with progressively larger Van Andel catheters passed over the guide wire through the cystoscope. Following dilation a 7.5F to 8.5F soft double pigtail catheter was easily advanced. All patients had good drainage on followup radiographic studies. The method is presented as an alternative to balloon dilation of lower ureteral strictures when the goal is placement of an adequate diameter indwelling ureteral stent. PMID- 8201692 TI - Subcutaneous urinary diversion: an alternative to percutaneous nephrostomy. AB - Nephrostomy has been the standard method of urinary diversion when placement of ureteral stents has failed in cancer patients. We describe our early experience with an alternative method of urinary diversion, the subcutaneous urinary diversion. This extra-anatomical urinary diversion was done in 5 patients during a 15-month interval. The diversion is created using a specially designed 7F double pigtail stent. The proximal end of the stent is inserted into the renal pelvis via a percutaneous nephrostomy puncture. A subcutaneous tunnel is created from the flank to the bladder down which the distal end of the stent is passed and via a suprapubic bladder puncture the stent is passed into the bladder. The stent is changed at 4-month intervals over a guide wire. Our early experience with this extra-anatomical method of urinary diversion suggests it to be a safe, effective and acceptable alternative to nephrostomy that improves quality of life. PMID- 8201693 TI - The tapered and reimplanted small bowel as a variation of the Mitrofanoff procedure: preliminary results. AB - Ten patients with a urethra that could not be catheterized and with absent appendixes underwent neobladder construction using an ileal segment fashioned to serve as the anti-incontinence mechanism. The latter was tapered and reimplanted following the guidelines of the Mitrofanoff procedure. Urinary reservoirs were constructed from detubularized segments of right colon, sigmoid colon and composite gastro-ileal combinations. Followup ranged from 9 to 21 months (mean 14.5). All patients presently catheterize the reservoir satisfactorily and are free of urinary leakage. Three patients (30%) experienced initial catheterization difficulties: 2 required endoscopic procedures and insertion of a stent, and 1 with stomal stenosis was successfully treated with a Y-V stoma plasty. One patient (10%) required a repeat ileal segment reimplantation due to urinary incontinence. The higher reoperation rate and the increased surgical complexity of this procedure compared with reconstructions using the ileocecal valve as part of the anti-incontinence mechanism make this operation a less attractive alternative in the creation of a continent urinary reservoir. However, with comprehension of the need for careful and detailed surgical technique in its creation, the tapered and reimplanted ileal segment is a successful choice as an alternative for the creation of an abdominal wall stoma when the appendix is unavailable. PMID- 8201694 TI - Flow cytometric bromodeoxyuridine/deoxyribonucleic acid bivariate analysis for predicting tumor invasiveness of upper tract urothelial cancer. AB - We previously reported that flow cytometric bromodeoxyuridine/deoxyribonucleic acid (DNA) bivariate analysis can provide important information on the malignant potential of bladder cancer. Therefore, in the current study we further evaluated upper tract urothelial tumors to clarify whether DNA/bromodeoxyuridine bivariate analysis can provide additional prognostic information on patients with upper tract urothelial tumor. A total of 43 upper tract urothelial tumors that were resected by nephroureterectomy was analyzed. Flow cytometric DNA ploidy and bromodeoxyuridine labeling were determined by an in vitro bromodeoxyuridine labeling method. DNA diploid tumors were associated with an 85.9% 3-year survival rate compared to 36.5% for DNA aneuploid tumors. On the other hand, 11 high bromodeoxyuridine labeled tumors demonstrated a 16.4% 3-year survival rate compared to 82.4% for those with low bromodeoxyuridine labeled tumors. Multivariate survival analysis using the Cox proportional regression model was performed to identify the most informative factors for prognosis, with the single most important factor being histological tumor stage. Nearly as important and the next factor to be chosen was tumor grade, followed by bromodeoxyuridine labeling index status. DNA ploidy status did not influence clinical outcome. Thereafter, when actuarial 3-year survival rates according to the bromodeoxyuridine labeling index status in grade 3 tumors were estimated, 68.4% and 16.7% 3-year survival rates were observed in cases of low and high bromodeoxyuridine labeling index tumors, respectively. These results indicate that flow cytometric bromodeoxyuridine/DNA bivariate analysis may be useful in dividing patients with grade 3 upper tract urothelial carcinoma into 2 different prognosis groups. PMID- 8201695 TI - Adjuvant cisplatin chemotherapy following cystectomy for bladder cancer: results of a prospective randomized trial. AB - Between April 1984 and May 1989, 77 eligible patients with invasive, nonmetastatic (stage M0) transitional cell carcinoma of the bladder were stratified after radical cystectomy and pelvic lymph node dissection on the basis of nodal status (stage pN0 versus pN1-2) and were randomly assigned to either observation or postoperative cisplatin chemotherapy (3 courses of 90 mg./m.2 cisplatin given for 3 consecutive days at monthly intervals). Patient eligibility included a creatinine clearance of greater than 60 ml. per minute. There were 40 eligible patients in the control group (median age 61 years) and 37 in the cisplatin group (median age 64 years). In regard to postoperative tumor stage and nodal status, there was no statistical difference between the 2 patient groups. In the cisplatin group 21 patients received the full dose, 9 required dose reduction and 7 refused treatment. Median followup was 5 years 9 months (range 3 to 8 years). Survival analysis showed no significant difference (log rank p = 0.65) between the 40 patients in the control group and the 37 in the cisplatin group. The survival rate at 5 years was 54% (95% confidence interval 39 to 69%) in the control group and 57% (95% confidence interval 40 to 74%) in the treatment group. Patients with cancer confined to the bladder wall (stage pT3a or less) had a 5-year overall survival rate of 70% and those with tumor growth in the perivesical fat or into the prostate (stages pT3b plus pT4a) had a 5-year overall survival rate of 40%. This difference in survival between the low stage subgroup (stages pT3a or less) and the high stage subgroup (pT3b plus pT4a) is highly significant (p = 0.0043). However, no difference between the controls and the cisplatin group was found within either the low or high stage subgroups. The reasons for failing to show a survival benefit from adjuvant high dose cisplatin monotherapy after radical cystectomy are discussed. PMID- 8201696 TI - Adult female urinary incontinence and childhood bedwetting. AB - A cross-sectional random population sample of women 30 to 59 years old was sent a questionnaire on urinary incontinence and, among other things, childhood bedwetting. Among 2,613 responders 17.0% reported prevalent urinary incontinence (14.7% stress provoked, 8.3% associated with urge, 6.8% stress and urge overlap, 2.2% occurring especially during sleep and 3.9% occurring especially when anxious), and 6.5% reported childhood bedwetting after age 5 years and 3.3% after age 10 years. Childhood bedwetting was associated with prevalent urge urinary incontinence (p < 0.01) and incontinence occurring during sleep (p < 0.0001) but was less marked with urinary incontinence occurring in situations of anxiety (p < 0.025). It is concluded that some individuals suffer a long-lasting disturbance of the balance between micturition and sleep processes. PMID- 8201697 TI - Abnormal detrusor function precipitating hydronephrosis identified by extended voiding cystometry. AB - Extended voiding cystometry was performed to elucidate the true detrusor function in a patient originally misdiagnosed during standard fill cystometry. This methodology allows for observation of an extended period of bladder activity and eliminates the artifacts of classical fill cystometry, which are detrusor instability and noncompliance. A chronically elevated intravesical pressure between contractions (inter-contraction pressure) representing high pressure residual urine, as well as frequent, high amplitude, long duration detrusor contractions during the storage phase and a large post-void residual urine volume were documented. These urodynamic abnormalities are known to precipitate hydroureteronephrosis in the absence of vesicoureteral reflux. PMID- 8201698 TI - Obstruction following anti-incontinence procedures: diagnosis and treatment with transvaginal urethrolysis. AB - We reviewed the charts of 41 patients who underwent transvaginal urethrolysis and resuspension of the bladder neck by the Raz technique for urethral obstruction with or without stress urinary incontinence following anti-incontinence surgery. We sought to evaluate the effectiveness of the procedure as well as to determine any factors that had an effect on the outcome of surgery. Patients were evaluated for obstruction and stress urinary incontinence by history, physical examination, video urodynamics (or multichannel urodynamics plus cystogram and voiding cystourethrography) and cystoscopy. All patients reported normal emptying before the procedure that caused obstruction. Several variables were evaluated for individual predictive values for outcome, including type of surgery causing obstruction, number of previous anti-incontinence procedures, urodynamic evidence of obstruction (high pressure, low flow), instability, concomitant stress urinary incontinence and total urinary retention, which were evaluated by the Fisher exact test, and the amount of post-void residual, bladder capacity, maximum detrusor pressure, maximum urinary flow and interval since surgery causing obstruction, which were evaluated by logistic regression analysis. Mean patient age was 59 years (range 26 to 86 years) and mean followup was 21 months. A total of 19 patients (46%) suffered from concurrent stress urinary incontinence, 23 (56%) had urodynamic evidence of obstruction (high pressure/low flow) and 6 (15%) had only radiographic or endoscopic evidence with a deviated or kinked urethra. Postoperatively, 29 patients (71%) voided normally without significant residuals. Eight patients (20%) remain on self-catheterization and 1 has persistent stress urinary incontinence. When individual variables were evaluated to determine the predictive values with respect to outcome of urethrolysis, only the preoperative post-void residual was statistically significant (the greater the post-void residual, the more likely was failure, p = 0.021). The presence or strength of the detrusor contraction preoperatively and pressure-flow analysis did not predict outcome. Of the patients with stress urinary incontinence 15 (79%) were cured and 3 (16%) were significantly improved with rare stress urinary incontinence not requiring protection. Overall, 33 patients (80%) had some benefit from surgery. Patients who emptied normally before and anti-incontinence procedure that causes obstruction or impaired emptying should not be excluded from urethrolysis based on low detrusor pressures or pressure-flow analysis alone. Simultaneous radiographic imaging and endoscopy may help to select certain patients with obstruction. PMID- 8201699 TI - Incontinent ileo-vesicostomy urinary diversion in the treatment of lower urinary tract dysfunction. AB - The combination of high spinal cord injury and neurovesical dysfunction can present formidable problems in urological management. The lack of upper extremity function often prevents intermittent catheterization and leads to alternative methods. A total of 23 patients underwent incontinent ileo-vesicostomy in an effort to gain a low pressure bladder and control of urinary soiling: 17 had been previously treated by catheter drainage, 9 had bladder and/or renal calculi, 9 experienced recurrent sepsis, and 7 had urethrocutaneous fistula and total urinary incontinence. Most patients had poorly compliant bladder dysfunction associated in 9 cases with poor urethral continence function. At a mean followup of 45 months (range 3 to 240 months) 22 of 23 patients had a low pressure reservoir with low pressure degrees of urine into a collection device. Complications included stomal stenosis in 3 patients and poor drainage across the ileovesical junction requiring revision in 2. One of these patients ultimately underwent ileal loop diversion. Upper tract function improved or remained stable in all patients. PMID- 8201700 TI - Correlation of venous noninvasive tests with the Society for Vascular Surgery/International Society for Cardiovascular Surgery clinical classification of chronic venous insufficiency. AB - PURPOSE: Noninvasive tests for the evaluation of chronic venous insufficiency (CVI) include quantitative photoplethysmography (QPG), air plethysmography, and duplex ultrasonography measurement of valve closure time (VCT). These tests have been shown to accurately identify the presence of CVI, define the disease, and locate the involved segments. However, the correlation of noninvasive assessment of CVI with the clinical severity (Society for Vascular Surgery/International Society for Cardiovascular Surgery staging) has not been addressed critically. METHOD: During an 18-month period, 74 limbs were prospectively evaluated with clinical examination, air plethysmography, QPG and duplex ultrasonography. RESULTS: We studied 52 patients with a mean age of 46 years. There were 14 stage 0 limbs, 14 stage 1, 15 stage 2, and 31 stage 3. We found significant differences (p < 0.05) between normal limbs and those with CVI only by VCT and QPG. There were also marked trends toward worsening mean values for reflux (VCT, QPG, and venous filling index) and venous hypertension (residual volume fraction) between stages 0 to 1, and 1 to 2; however, there was a large degree of overlap between all groups. No test discriminated stage 2 from 3. Assessment of calf muscle pump function with ejection fraction showed no difference between any groups. CONCLUSION: The Society for Vascular Surgery/International Society for Cardiovascular Surgery criteria for CVI staging distinguishes ulcerated limbs (stage 3) from those with nonulcerating skin changes (hyperpigmentation, brawny edema, and subcutaneous fibrosis) (stage 2). However, we were not able to distinguish these groups by available noninvasive methods. This may imply that these tests are not accurate enough or that the progression from lipodermatosclerosis to frank ulceration is not accounted for by large-vessel hemodynamic changes, but rather by microcirculatory alterations. PMID- 8201701 TI - Neuropathy after cardiac catheterization: incidence, clinical patterns, and long term outcome. AB - PURPOSE: Neuropathy is a rare, but potentially morbid, complication of cardiac catheterization. In this study, we report the incidence of this complication and describe its clinical presentation, cause, and natural history. METHODS: Between 1988 and 1993, 9585 cardiac catheterizations were performed at this institution. Patients in whom femoral neuropathy developed were identified through a cardiology registry. Hospital and outpatient records and personal interviews were used to determine the presentation and clinical course of each of these patients. RESULTS: Peripheral neuropathy developed in 20 patients (incidence = 0.21%). Two clinical patterns emerged. In 16 patients, large retroperitoneal hematomas were documented by either computed tomography scanning or by physical examination. These patients were admitted with a lumbar plexopathy involving the femoral, obturator, or lateral femoral cutaneous nerves. Long-term follow-up revealed persistent mild sensory neuropathy in five patients and a mild motor deficit in one. In four patients a groin hematoma or false aneurysm developed which resulted, in paresthesias involving the medial and intermediate cutaneous branches of the femoral nerve. Symptoms completely resolved in all four patients, although false aneurysms were surgically repaired in two. CONCLUSIONS: Neuropathy after cardiac catheterization can be initially disabling, but it is usually completely reversible. Operation is recommended only for coexisting complications. PMID- 8201702 TI - Carotid endarterectomy in awake patients: its safety, acceptability, and outcome. AB - PURPOSE: The purpose of this study was to determine the safety and efficacy of performing carotid endarterectomy procedures with the patient receiving cervical block anesthetic. METHODS: Over the last 14 years, 654 carotid endarterectomy procedures were performed with patients receiving regional anesthetic. Intraluminal shunts were placed on demand, if neurologic changes with clamping of the carotid artery developed in the patient. During the same period, 419 cases were done with the patients receiving general anesthetic. Choice of anesthetic was based on surgeon and patient preference. RESULTS: In the regional anesthetic group the indications for operation included transient ischemic attack (311), asymptomatic hemodynamically significant stenosis (146), amaurosis fugax (106), stroke (86), restenosis (3), and aneurysm (2). Shunts were used in 46 of 654 cases (7%). Conversion from regional to general anesthetic was required in seven patients (1.1%). The operative mortality rate was 0.76% (5 of 654). Permanent nonfatal neurologic deficits occurred in 0.76% (5 of 654), and temporary neurologic deficits occurred in 1.07% (7 of 654). CONCLUSIONS: On the basis of these results, we believe regional cervical block anesthetic is an acceptable option to the routine use of shunts performed with the patient receiving general anesthetic during carotid endarterectomy. In addition, the ability to continuously assess the awake patient receiving cervical block may contribute to a decrease in perioperative stroke and mortality rates while simplifying functional cerebral monitoring during carotid endarterectomy. PMID- 8201703 TI - A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia. AB - PURPOSE: Despite the widespread use of intraarterial thrombolytic therapy for peripheral arterial occlusive disease, a randomized study comparing its efficacy with that of operative intervention has never been performed. This study evaluates the potential of intraarterial urokinase infusion to provide clinical benefits in patients with acute peripheral arterial occlusion. METHODS: Patients with limb-threatening ischemia of less than 7 days' duration were randomly assigned to intraarterial catheter-directed urokinase therapy or operative intervention. Anatomic lesions unmasked by thrombolysis were treated with balloon dilation or operation. The primary end points of the study were limb salvage and survival. RESULTS: A total of 57 patients were randomized to the thrombolytic therapy group, and 57 patients were randomized to the operative therapy group. Thrombolytic therapy resulted in dissolution of the occluding thrombus in 40 (70%) patients. Although the cumulative limb salvage rate was similar in the two treatment groups (82% at 12 months), the cumulative survival rate was significantly improved in patients randomized to the thrombolysis group (84% vs 58% at 12 months, p = 0.01). The mortality differences seemed to be primarily attributable to an increased frequency of in-hospital cardiopulmonary complications in the operative treatment group (49% vs 16%, p = 0.001). The benefits of thrombolysis were achieved without significant differences in the duration of hospitalization (median 11 days) and with only modest increases in hospital cost in the thrombolytic treatment arm (median $15,672 vs $12,253, p = 0.02). CONCLUSIONS: Intraarterial thrombolytic therapy was associated with a reduction in the incidence of in-hospital cardiopulmonary complications and a corresponding increase in patient survival rates. These benefits were achieved without an appreciable increase in the duration of hospitalization and with only modest increases in hospital cost, suggesting that thrombolytic therapy may offer a safe and effective alternative to operation in the initial treatment of patients diagnosed with acute limb-threatening peripheral arterial occlusion. PMID- 8201704 TI - Diabetes mellitus and experimental vein graft structure and function. AB - PURPOSE: Diabetes mellitus is a known risk factor for accelerated atherosclerosis and for postangioplasty restenosis. METHODS: This study examines the effect of chronic, uncontrolled, alloxan-induced diabetes on the structure and vasomotor function of vein bypass grafts in 20 male New Zealand white rabbits with diabetes and in 10 controls. After 8 weeks of diabetes, a common carotid vein bypass graft was performed. Four weeks after operation, vein grafts and contralateral jugular veins were harvested. RESULTS: Diabetes induced a twofold increase in the vein graft intimal thickness compared with control. There was no change in medial thickness. Electron microscopy of the vein grafts in diabetes revealed intercellular gaps in the endothelium lining and abnormal endothelial cell junctions compared with controls. Diabetes significantly increased the maximal contractions generated in vein grafts to all contractile agonists tested without any change in sensitivity. CONCLUSIONS: This study demonstrates that diabetes alters endothelial cell structure and increases the development of intimal hyperplasia with increased maximal contractility in vein grafts and therefore suggests that the vein grafts in diabetes are more susceptible to early stenosis. PMID- 8201706 TI - Augmentation of blood flow in limbs with occlusive arterial disease by intermittent calf compression. AB - PURPOSE: This study was designed to investigate the effect of intermittent calf compression on popliteal arterial blood flow and to see how flow is influenced by position of the subject and by arterial blood pressure at the ankle. METHODS: Volume flow in the popliteal artery of subjects in the sitting and prone positions was measured with duplex ultrasonography before inflation and immediately after deflation of a pneumatic cuff placed around the calf. Eleven legs of control subjects and 41 legs of patients with symptoms (32% patients with diabetes) with decreased ankle pressure were studied. Cuffs were inflated for 2 seconds at pressures ranging from 20 to 120 mm Hg. RESULTS: An increase in arterial blood flow of two to eight times (mean 4.4 +/- 2.0) was found on deflation of the cuff in seated control subjects. Little change in flow was observed when the subjects were in the prone position. In seated patients with arterial obstruction, the mean increase in arterial flow was 3.2 +/- 1.6 times the resting flow. Little correlation was found between the maximum increase in flow and the ankle/brachial index. CONCLUSIONS: An increased arteriovenous pressure gradient accounts for some but not all of the flow increase, much of which must be attributable to transient vasodilatation. Because the increase in flow does not depend on an increased inflow pressure and was not adversely affected by a low resting ankle-brachial pressure index or a low toe-pressure, intermittent external limb compression may deserve investigation as a possible adjunct to the nonoperative treatment of patients with severe arterial insufficiency. PMID- 8201705 TI - Prevention of paraplegia during thoracic aortic cross-clamping: importance of patent internal mammary arteries. AB - PURPOSE: Unexplained anatomic and physiologic factors account for the unacceptably high rate of paraplegia/paresis after thoracoabdominal aortic reconstruction. We assessed the neurologic significance of patent internal mammary arteries (IMAs) in a novel rat model of aortic clamping in which the aortic origins of the intercostal arteries (ICAs) were occluded. METHODS: Twenty anesthetized, intubated, and halothane-ventilated adult male rats had catheters placed in the carotid and femoral arteries. ICAs arising from the aorta were divided at their origins through a left thoracotomy. IMAs were either divided (IMA-OUT, n = 10) or left intact (IMA-IN, n = 10). Proximal and distal descending aortic clamps were placed for 7 minutes. A neurologic deficit score (NDS) was assigned at 1, 4, 18, 24, and 48 hours by use of an established scoring system. RESULTS: The mean IMA-IN NDS was statistically better than the mean IMA-OUT NDS at 1, 4, 18, and 24 hours with p = 0.0005, 0.0014, 0.0098, and 0.0151, respectively. Moreover, the mortality rate in the IMA-OUT group was statistically greater than in the IMA-IN group (p = 0.0036). CONCLUSION: In this model, patent IMAs prevent paraplegia when the ICAs are occluded at their aortic origin and the aorta is clamped for 7 minutes. PMID- 8201707 TI - The development of valvular incompetence after deep vein thrombosis: a follow-up study with duplex scanning. AB - PURPOSE: Duplex ultrasonography with distal cuff deflation was used to establish the physiologic reflux duration in different segments of the deep venous system in healthy individuals, and to document the occurrence of deep vein valve incompetence in patients after deep vein thrombosis (DVT). METHODS: Two hundred fifty-two vein segments in 42 legs of 21 healthy individuals and 160 deep vein segments in 27 patients with phlebographically documented DVT were examined with duplex scanning. RESULTS: The duration of reflux in healthy subjects was significantly shorter in distal deep vein segments. Ninety-five percent of the values were less than 0.88, 0.8, 0.8, 0.28, 0.2, and 0.12 seconds, respectively, for the common femoral, superficial femoral, deep femoral, popliteal, and posterior tibial vein (at midcalf and ankle level). The 95 percentile for reflux duration in the superficial venous system was 0.5 seconds for all vein segments, regardless of the location. No significant correlation was found between the reflux peak flow velocity and reflux duration (R = 0.6). The reflux peak flow velocity is therefore not useful as a parameter of the degree of reflux. The patient group was examined with an interval of 18 to 51 months (mean 34 months) after DVT. Forty-five percent of the initially affected segments showed valve incompetence at follow-up (n = 54); only three of 40 segments initially free from thrombus showed pathologic reflux at follow-up (p < 0.01). Reflux durations in most of the incompetent vein segments were two or more times the normal value of reflux duration. The highest prevalence of valve incompetence was found in the superficial femoral and popliteal vein segment (p < 0.01). None of the patients showed valve incompetence at all levels of the deep venous system. A significant (p = 0.04) relation was found between the extent of the initial thrombosis and the number of refluxing vein segments at follow-up, but no correlation was found between the extent of initial thrombosis and the late clinical symptoms (p = 0.16); clinical symptoms could not be related to the number of incompetent vein segments. CONCLUSIONS: Duplex scanning allows a good discrimination between physiologic and abnormal reflux duration and is an important tool in the evaluation of the postthrombotic limb. Early assessment after DVT may have prognostic value in individual patients. PMID- 8201708 TI - Influence of angle on wall shear stress distribution for an end-to-side anastomosis. AB - PURPOSE: The purpose of this article was to study the effects of anastomotic angle on the wall shear stress distribution for end-to-side anastomosis models under pulsatile flow conditions. METHOD: The photochromic tracer technique was used to visualize the flow field and to determine the instantaneous wall shear stress at multiple locations simultaneously. Models with angles of 20, 30, 45, and 60 degrees were examined. RESULTS: For all angles, low shear stress was present at the heel and on the bed opposite the heel of the anastomosis apparently as a result of the complete occlusion of the proximal end of the host vessel. Near the toe, increased flow separation occurred with increasing angle. On the bed across from the toe, increasing the angle led to increased shear stress. In addition, in this region the anastomotic angle significantly altered other properties of the shear stress field such as the mean and peak-to-peak magnitudes and cycle-to-cycle fluctuations. CONCLUSIONS: This study provides quantitative data on the wall shear stress distribution within an end-to-side anastomosis and its relation to the anastomotic angle. The results are discussed in terms of possible roles of shear-induced intimal hyperplasia. PMID- 8201709 TI - Microangiopathy of the skin and the effect of leg compression in patients with chronic venous insufficiency. AB - PURPOSE: The reasons for the efficacy of leg compression in the treatment of chronic venous insufficiency are not clear. We have used laser Doppler fluxmetry to assess the effect of external compression on the skin microcirculation. METHODS: Fifteen patients with lipodermatosclerosis caused by chronic venous insufficiency and 15 control subjects were studied in the supine and sitting positions. The laser Doppler probe, incorporated in a polyethylene chamber, was applied to the lower leg underneath a blood pressure cuff. Pressures were applied from 10 to 100 mm Hg in increments of 10 mm Hg. A computer data logging system recorded laser Doppler flux blood cell velocity, and concentration of moving blood cells. RESULTS: In patients in the supine position, 20 mm Hg compression resulted in a median increase of 33% in laser Doppler flux, and a median increase of 79% in blood cell velocity, but higher pressures caused a progressive decrease in laser Doppler flux and blood cell velocity. With the patient in the sitting position, compression up to 60 mm Hg caused an increase in laser Doppler flux (median percentage increase at 20 mm Hg compression 84%) and blood cell velocity (median percentage increase at 20 mm Hg compression 22%). At 20 mm Hg compression, the concentration of moving blood cells decreased in the supine position (median percentage fall 27%) but did not change significantly in the dependent position. The effects of compression in control subjects were similar to those in patients, but to a lesser degree. CONCLUSION: Our study suggests that compression treatment may achieve part of its effect by causing an increase in the microcirculatory flow velocity. PMID- 8201710 TI - Aortic dissection originating in the suprarenal abdominal aorta. AB - Spontaneous dissection of the abdominal aorta originating from the suprarenal aorta is very rare. Previous reports attest to the lethal nature of this disorder. This case represents the first report of successful repair of a spontaneous suprarenal abdominal aortic dissection by graft insertion with obliteration of both the entrance tear and the false lumen with reimplantation of the visceral vessels. PMID- 8201711 TI - Traumatic aortocaval fistulas of late diagnosis. PMID- 8201712 TI - Does female sex adversely affect long-term patency of peripheral arterial reconstructions? PMID- 8201713 TI - Suturing the calcified aorta. PMID- 8201714 TI - Robert R. Linton, MD: a legacy of "doing it right". PMID- 8201715 TI - Are peroneal artery bypass grafts hemodynamically inferior to other tibial artery bypass grafts? AB - PURPOSE: Many authors have reported excellent long-term patency rates of peroneal artery bypasses. It has been suggested, however, that the hemodynamic result of the peroneal bypass is inferior to that of other infrapopliteal artery bypasses, making it suboptimal in patients with forefoot ischemic tissue loss. A retrospective review of 118 recent infrainguinal vein grafts (36 peroneal, 27 anterior tibial, 35 posterior tibial, 20 popliteal) was undertaken to assess and compare the hemodynamic results for each group. METHODS: We reviewed the hemodynamic results of 36 peroneal bypass grafts assessed by preoperative and postoperative ankle-brachial index and transmetatarsal pulse volume recording, duplex scan-derived distal graft peak systolic flow velocity, and intraoperatively measured outflow resistance. These results were compared with a concurrent series of anterior tibial, posterior tibial, and popliteal artery bypass grafts. All but one of the infrapopliteal bypass grafts were performed for limb salvage, and 65% of patients had ischemic ulcerations or gangrene. RESULTS: There was no difference in postoperative ankle-brachial index, postoperative transmetatarsal pulse volume recording, peak systolic flow velocity, or measured outflow resistance among the four different outflow groups. All patients with peroneal bypass grafts had healed wounds within a mean follow-up period of 17 months. There were no hemodynamic failures. CONCLUSION: Peroneal artery bypass grafts achieved hemodynamic results equivalent to anterior tibial, posterior tibial, and popliteal artery bypass grafts. PMID- 8201716 TI - Vein adaptation to the hemodynamic environment of infrainguinal grafts. AB - PURPOSE: Although arteries appear to remodel in response to changes in hemodynamic parameters such as shear stress, little is known about functioning human vein grafts. This study was designed to explore diameter changes in human saphenous vein grafts after infrainguinal bypass. METHODS: We used duplex ultrasonography to measure hemodynamic variables that might affect the diameter of 48 in situ saphenous vein grafts during the first year after infrainguinal arterial bypass. Volumetric flow rate, average velocity, peak systolic velocity, and vein diameter in the proximal and distal thirds of these grafts were each measured at 1 week and at 3, 6, and 12 months after operation. Veins were divided into three groups based on initial size (1 week after bypass) in the below-knee segment: small, < 3.5 mm diameter; medium, 3.5 to 4 mm diameter; and large, > 4 mm diameter. RESULTS: Distal vein diameters at 1 week for small, medium, and large grafts were 2.9 +/- 0.1, 3.7 +/- 0.1, and 4.3 +/- 0.1 mm, respectively (p < 0.001), but by 12 months these diameters were 3.6 +/- 0.2, 3.8 +/- 0.2, and 3.9 +/- 0.2 mm, respectively (p = 0.54). Large veins decreased in diameter, whereas small veins increased in diameter, as confirmed by linear regression of percent change in diameter versus initial vein graft diameter (r = -0.62, p < 0.001). Volumetric flow rate, peak systolic velocity, and shear stress also tended to approach uniform values over time. Of the hemodynamic variables studied, the best predictor of diameter change was shear stress (linear regression of percent change in diameter vs shear stress, r = 0.67, p < 0.001). Veins with a diameter increase greater than 10% over time had significantly higher initial shear stress than veins with a diameter decrease greater than 10% over time (28.6 +/- 3.8 vs 13.1 +/- 1.8 dynes/cm2, p < 0.01), whereas initial volumetric flow rates in these two groups were similar (135 +/- 23 vs 130 +/- 15 ml/min). CONCLUSIONS: Infrainguinal in situ vein graft diameter, volume flow rate, peak systolic velocity, and shear stress all tend to stabilize at uniform values regardless of the initial vein graft diameter. Of the hemodynamic variables studied, shear stress is most strongly associated with the change in diameter over time. Thus human saphenous vein appears to be capable of adapting to its hemodynamic environment after arterial grafting by modulating diameter to normalize shear stress. PMID- 8201717 TI - The cost-effectiveness of early surgery versus watchful waiting in the management of small abdominal aortic aneurysms. AB - PURPOSE: The purpose of this study was to compare the relative cost-effectiveness of two clinical strategies for managing 4 to 5 cm diameter abdominal aortic aneurysms (AAAs): early surgery (repair 4 cm AAA when diagnosed) versus watchful waiting (monitor AAA with ultrasound size measurements every 6 months and repair if the diameter reaches 5 cm). METHODS: We used a Markov decision tree to compute the expected survival in quality-adjusted life years (QALYs) for each strategy, based on literature-derived estimates for the probabilities of different outcomes in this model. We determined hospital costs for patients undergoing elective and emergency AAA repair at our center. With standard methods of cost accounting, we then calculated the additional cost per year of life saved by early surgery compared with watchful waiting (cost-effectiveness ratio, dollars/QALY). RESULTS: Mean hospital costs for elective and emergency AAA repair were $24,020 and $43,208, respectively (1992 dollars). For our base-case analysis (60-year-old men with 4 cm diameter AAAs, with 5% elective operative mortality rate and 3.3% annual rupture rate), early surgery improved survival by 0.34 QALYs compared with watchful waiting, at an incremental cost of $17,404/QALY. Increased elective surgical mortality rate, decreased AAA rupture risk, and increased patient age all reduced the cost-effectiveness of early surgery. Future increases in elective operative risk, noncompliance with ultrasound follow-up and increased threshold size for elective AAA repair during watchful waiting all improved the cost effectiveness of early surgery. Future increases in elective operative risk, noncompliance with ultrasound follow-up and increased threshold size for elective AAA repair during watchful waiting all improved the cost-effectiveness of early surgery. CONCLUSIONS: The cost effectiveness of early surgery for 4 cm diameter AAAs in carefully selected patients compares favorably with that of other commonly accepted preventive interventions such as hypertension screening and treatment. With an upper limit of $40,000/QALY as an "acceptable" cost effectiveness ratio, early surgery appears to be justified for patients 70 years old or younger, if the AAA rupture risk is 3%/year or more and the elective operative mortality rate is 5% or less. Although not a substitute for clinical judgment, this cost-effectiveness analysis delineates the essential tradeoffs and uncertainties in treating patients with small AAAs. PMID- 8201718 TI - Randomized prospective study of angioscopically assisted in situ saphenous vein grafting. AB - PURPOSE: A study was conducted to test the hypothesis that angioscopically assisted valve lysis and vein branch identification during in situ saphenous vein bypass would reduce technical causes of graft failure, local operative morbidity, and hospital stay. METHODS: Patients requiring primary bypass to an infrageniculate artery were randomly assigned to undergo in situ saphenous vein bypass with valvulotomy and branch identification either under angioscopic visualization with use of short intermittent incisions (scope) or under direct vision with use of a continuous incision (no scope). Data on operative details, morbidity, hospital length of stay, and graft patency were collected prospectively and compared. RESULTS: Fifty-nine patients were enrolled (32 scope, 27 no scope). There were no significant differences between study groups in the incidence of diabetes, claudication versus critical ischemia indications for surgery, or popliteal versus infrapopliteal location of distal anastomoses. Rates of wound complications (9.3% and 3.7%), early graft occlusion (6.2% and 7.4%), and mean postoperative hospital stay (8.0 and 8.6 days) were statistically similar for the scope and no scope groups, respectively. Differences in cumulative secondary patency rates at 48 months (79% scope, 91% no scope) were also insignificant. CONCLUSIONS: Use of angioscopy to assist with preparation of the in situ vein for infrageniculate grafting appears to have no impact on local operative morbidity, hospital length of stay, or midterm graft patency. PMID- 8201719 TI - In war-torn Balkans, US military medical support nears 2-year mark. PMID- 8201720 TI - From the Health Care Financing Administration. PMID- 8201721 TI - From the Centers for Disease Control and Prevention. Human immunodeficiency virus transmission in household settings--United States. PMID- 8201722 TI - From the Centers for Disease Control and Prevention. Populations at risk from particulate air pollution--United States, 1992. PMID- 8201723 TI - Cancer: medical history and the framing of a disease. PMID- 8201724 TI - A piece of my mind. Heartpains. PMID- 8201725 TI - Authorship! Authorship! PMID- 8201726 TI - Authorship! Authorship! PMID- 8201727 TI - Hair nicotine and cotinine in women and newborn infants. PMID- 8201728 TI - Cutaneous hypersensitivity reaction to digoxin. PMID- 8201729 TI - Goldenhar's syndrome associated with tamoxifen given to the mother during gestation. PMID- 8201730 TI - Routine childhood varicella vaccination. PMID- 8201731 TI - Increasing completion of advance directives. PMID- 8201732 TI - Increasing completion of advance directives. PMID- 8201733 TI - Detection of carotid stenosis by physical examination. PMID- 8201734 TI - Regular source of ambulatory care and medical care utilization by patients presenting to a public hospital emergency department. AB - OBJECTIVE: To determine the regular source of care and the relationship between usual provider and use of medical services among ambulatory emergency department patients. DESIGN: Cross-sectional survey. SETTING: A public hospital in Los Angeles County, California. PATIENTS: A total of 1190 stable, ambulatory adults presenting to the emergency department during a 2-week period. MAIN OUTCOME MEASURES: Self-reported regular source of care, usual health status, and recent physician visits. RESULTS: A total of 16% of the patients identified an emergency department as their regular source of care. One fourth of this group reported fair or poor health. African Americans and Latinos were more likely than whites to identify an emergency department as their regular source of care. Patients who identified an emergency department as their regular source of care had 25% fewer physician visits and were less likely to have seen a physician during the preceding 3 months than patients who were usually seen in an office or clinic (relative risk, 0.45; 95% confidence interval, 0.28 to 0.70). Of all patients, 56% identified a regular source of care other than an emergency department, but 24% to 36% of all their recent physician visits still occurred in an emergency department. CONCLUSION: Our patients rely heavily on emergency departments for ambulatory physician visits, regardless of their reported regular source of care. However, patients who identify an emergency department as their regular source of ambulatory care used physician services less frequently than patients with access to providers in other settings. These issues require further evaluation with population-based surveys. PMID- 8201735 TI - A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. AB - OBJECTIVE--To determine the safety and efficacy of a new combination treatment for patients with Clostridium difficile-associated disease (CDD). The treatment combines the yeast Saccharomyces boulardii with an antibiotic (vancomycin hydrochloride or metronidazole). DESIGN--A double-blind, randomized, placebo controlled, parallel-group intervention study in patients with active CDD. Patients received standard antibiotics and S boulardii or placebo for 4 weeks, and were followed up for an additional 4 weeks after therapy. Effectiveness was determined by comparing the recurrence of CDD in the two groups using multivariate analysis to control for other risk factors for CDD. SETTING- National referral study of ambulatory or hospitalized patients from three main study coordinating centers. PATIENTS--A total of 124 eligible consenting adult patients, including 64 who were enrolled with an initial episode of CDD, and 60 who had a history of at least one prior CDD episode. Patients who were immunosuppressed due to acquired immunodeficiency syndrome or cancer chemotherapy within 3 months were not eligible. INTERVENTION--Treatment with oral S boulardii (1 g/d for 4 weeks) or placebo in combination with a standard antibiotic. MAIN OUTCOME MEASURE--Recurrence of active CDD. RESULTS--A history of CDD episodes dramatically increased the likelihood of further recurrences. Multivariate analysis revealed that patients treated with S boulardii and standard antibiotics had a significantly lower relative risk (RR) of CDD recurrence (RR, 0.43; 95% confidence interval, 0.20 to 0.97) compared with placebo and standard antibiotics. The efficacy of S boulardii was significant (recurrence rate 34.6%, compared with 64.7% on placebo; P = .04) in patients with recurrent CDD, but not in patients with initial CDD (recurrence rate 19.3% compared with 24.2% on placebo; P = .86). There were no serious adverse reactions associated with S boulardii. CONCLUSIONS--The combination of standard antibiotics and S boulardii was shown to be an effective and safe therapy for these patients with recurrent CDD; no benefit of S boulardii was demonstrated for those with an initial episode of CDD. PMID- 8201736 TI - Outcome of hospitalized injured patients after institution of a trauma system in an urban area. AB - OBJECTIVE: To determine if risk of death for hospitalized injured patients changes when an urban trauma system is implemented. DESIGN: An analysis of the risk of death in hospitalized injured patients in 1984 and 1985 (pretrauma system), 1986 and 1987 (early trauma system), and 1990 and 1991 (established trauma system) using hospital discharge abstract data. SETTING: A total of 18 acute care hospitals in the four-county area encompassing Portland, Ore. PATIENTS: A cohort of 70,350 hospitalized patients with at least one discharge diagnosis indicating injury. MAIN OUTCOME MEASURE: Death during hospitalization. RESULTS: After the trauma system was established, 77% of patients in the region with an Injury Severity Score (ISS) of 16 or greater were admitted to level I trauma centers. More than 72% of patients with an ISS less than 16 were hospitalized in nontrauma centers. Risk of death for injured patients hospitalized at level I trauma centers declined after the trauma system was established (odds ratio, 0.65; 95% confidence interval, 0.51 to 0.81). Patients who died in trauma centers after institution of the trauma system were younger and had more severe injuries, and the majority died within 1 day of admission, whereas patients who died in nontrauma centers died a median of 5 days after admission. CONCLUSION: Establishment of a trauma system shifted the more seriously injured patients to level I trauma centers, where there was a significant reduction in the adjusted death rate. PMID- 8201737 TI - Obstacles predicting lack of a regular provider and delays in seeking care for patients at an urban public hospital. AB - OBJECTIVE: To determine the correlation among obstacles to medical care, lack of a regular source of care, and delays in seeking care. DESIGN: Cross-sectional survey of patients presenting for ambulatory care during a 7-day period. Multiple logistic regression models were used to identify obstacles independently associated with outcome variables. SETTING: Urban public hospital. PATIENTS: A total of 3897 disadvantaged and predominantly minority patients. MAIN OUTCOME MEASURES: Lack of a regular source of medical care and delay in seeking medical care for a new problem. RESULTS: The majority (61.6%) of patients reported no regular source of care. Of 2341 patients reporting a new medical problem, 48.4% waited more than 2 days before seeking medical care. No health insurance (adjusted odds ratio [OR], 2.2; 95% confidence interval [CI], 1.89 to 2.61), no transportation (OR, 1.44; 95% CI, 1.23 to 1.70), exposure to violence (OR, 1.21; 95% CI, 1.08 to 1.45), and living in a supervised setting (OR, 1.50; 95% CI, 1.00 to 2.25) were independent predictors of lack of a regular source of care. No insurance (OR, 1.24; 95% CI, 1.02 to 1.51), no transportation (OR, 1.45; 95% CI, 1.19 to 1.77), and less than a high school education (OR, 1.22; 95% CI, 1.08 to 1.49) were independent predictors of delaying care for a new medical problem. CONCLUSIONS: Obstacles in addition to lack of insurance impede provision of medical care to disadvantaged patients. The adoption of universal health care coverage alone will not guarantee access to appropriate medical care. PMID- 8201738 TI - Computer networks as a medical resource. Accessing and using the Internet. PMID- 8201739 TI - The effectiveness of the nicotine patch for smoking cessation. A meta-analysis. AB - OBJECTIVE: To estimate the overall efficacy and optimal use of the nicotine patch for treating tobacco dependence. DATA SOURCES: Nicotine patch efficacy studies published through September 1993, identified through MEDLINE, Psychological Abstracts, and Food and Drug Administration new drug applications. STUDY SELECTION: Double-blind, placebo-controlled nicotine patch studies of 4 weeks or longer with random assignment of subjects, biochemical confirmation of abstinence, and subjects not selected on the basis of specific diseases (eg, coronary artery disease). DATA EXTRACTION: Pooled abstinence rates and combined odds ratios (ORs) at end of treatment and 6-month follow-up were examined overall and in terms of patch type (16-hour vs 24-hour), patch treatment duration, dosage reduction (weaning), counseling format (individual vs group), and intensity of adjuvant behavioral counseling. DATA SYNTHESIS: Across 17 studies (n = 5098 patients) meeting inclusion criteria, overall abstinence rates for the active patch were 27% (vs 13% for placebo) at the end of treatment and 22% (vs 9% for placebo) at 6 months. The combined ORs for efficacy of active patch vs placebo patch were 2.6 at the end of treatment and 3.0 at 6 months. The active patch was superior to the placebo patch regardless of patch type (16-hour vs 24-hour), patch treatment duration, weaning, counseling format, or counseling intensity. The 16-hour and 24-hour patches appeared equally efficacious, and extending treatment beyond 8 weeks did not appear to increase efficacy. The pooled abstinence data showed that intensive behavioral counseling had a reliable but modest positive impact on quit rates. CONCLUSIONS: The nicotine patch is an effective aid to quitting smoking across different patch-use strategies. Active patch subjects were more than twice as likely to quit smoking as individuals wearing a placebo patch, and this effect was present at both high and low intensities of counseling. The nicotine patch is an effective smoking cessation aid and has the potential to improve public health significantly. PMID- 8201740 TI - Viral imitations of host defense proteins. Flattery that turns to battery. PMID- 8201741 TI - Nonurgent emergency department visits. Meeting an unmet need. PMID- 8201742 TI - Traveling the new information highway. PMID- 8201743 TI - Finland's health care system. Universal access to health care in a capitalistic democracy. PMID- 8201744 TI - Nutritional and metabolic characterization of a thiamine-deficient rat model. AB - The effects of a thiamine-deficient diet on plasma and tissue vitamin concentrations and on whole-body glucose metabolism were assessed. Male Sprague Dawley rats (175 to 200 g body weight) fed a thiamine-deficient (TD) or nutritionally complete purified diet were used for plasma thiamine mononitrate and monophosphate and for red blood cell and tissue thiamine pyrophosphate (TPP) determinations weekly for up to 5 weeks. Additional rats were used for assessment of basal glucose kinetics by using a primed constant infusion of [3-3H]glucose. Plasma thiamine mononitrate levels decreased 60% at 1 week and were undetectable after 5 weeks on the diet. Plasma thiamine monophosphate decreased 80% after 1 week on the TD diet, and levels were undetectable after 4 weeks on the diet. Red blood cell TPP in the TD group decreased progressively with time: 54% at 1 week, 86% at 3 weeks, and 92% at 5 weeks. At 1 and 4 weeks, the decrease in tissue TPP was significant in the liver (65% and 89%, respectively), gut (52% and 94%, respectively), spleen (40% and 60%, respectively), and skeletal muscle (37% and 76%, respectively), with the brain (7% and 84%, respectively) showing the slowest initial rate of depletion. The TD diet did not alter plasma glucose concentrations, but it increased plasma lactate by 75% and plasma pyruvate by 50% to 75%. Rates of hepatic glucose production and peripheral glucose utilization were not different between the control and TD rats at 2 weeks, but they were 25% higher in the TD rats after 6 weeks on the diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201745 TI - Hydrolysis of mixed lipid emulsions containing medium-chain and long-chain triacylglycerol with lipoprotein lipase in plasma-like medium. AB - We explored the effects of plasma-like conditions on hydrolysis of medium-chain triglyceride (MCT) and long-chain triglyceride (LCT) emulsions at different mixing ratios and the effect of the physical method of mixing on lipoprotein lipase hydrolysis of mixed emulsions in vitro. Mixed emulsions with two different mixing ratios, 50% MCTs with 50% LCTs and 70% MCTs with 30% LCTs by weight, were studied. Emulsions containing both MCT and LCT oils blended in the same emulsion particle were compared with mixtures of separate pure MCT emulsion particles and pure LCT particles. MCT hydrolysis was always greater than LCT hydrolysis. In a plasma-free tris(hydroxymethyl)aminomethane-albumin buffer at pH 8.5, the physical method of mixing had substantial effects on hydrolysis; blended emulsions of MCTs and LCTs were hydrolyzed better than separate mixes of pure MCT and pure LCT particles, ie, more total free fatty acids were released. In plasma free systems, there were no differences in rates of hydrolysis of LCTs or MCTs (as individual triglycerides) between the two different mixing ratios of 50:50 and 70:30. However, the presence of plasma markedly diminished the differences in hydrolysis between blended vs separately mixed emulsions at pH 7.4. Also, in plasma-like incubation buffer, the rates of hydrolysis of MCTs and LCTs in emulsions with 50:50 or 70:30 MCT to LCT ratios reflected the respective amounts of MCT and LCTs in the emulsions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201746 TI - Biliary amino acid and glutathione secretion in response to amino acid infusion in the isolated rat liver. AB - The intravenous infusion of amino acid solutions has been associated with cholestatic liver injury in hospitalized patients and in laboratory animals. In the isolated rat liver, we recently showed that the acute decrease in bile flow, previously reported by other investigators, is dose related, reversible, and associated with dose-related increases in total biliary amino acid concentrations. In the present study, we characterized the effects of graded infusions of amino acid solutions, with and without taurocholate, on biliary secretion of individual amino acids and glutathione, an important regulator of bile flow. Livers from young adult male rats were perfused with an amino acid solution for 1 hour and allowed to recover for 30 minutes. Infusion of the amino acid solution was associated with dose-related increases in biliary concentrations of most amino acids included in the amino acid solution. Infusion of amino acid solutions resulted in a decreased bile/perfusate ratio of most amino acids, which were secreted into bile in amounts approximating their calculated uptake from the infusate. The inclusion of taurocholate in the infusate was associated with lower biliary concentrations of each individual amino acid and significant decreases in biliary total, reduced, and oxidized glutathione. Further investigation of the relationship between these changes in biliary amino acids and glutathione concentrations and the cholestasis associated with infusion of amino acid solutions may provide insights into the mechanism by which amino acids induce such cholestasis. PMID- 8201747 TI - Effect of glutamine on phagocytosis and bacterial killing by normal and pediatric burn patient neutrophils. AB - Glutamine is essential for the function of lymphocytes and macrophages, where it serves, among other things, as a source of energy. Little information is available concerning the fuel that polymorphonuclear cells use for their metabolic and bactericidal functions. It was the purpose of this study to determine whether glutamine would enhance the in vitro bactericidal function of normal neutrophils and whether the amino acid would restore the observed impaired function in burn patients to or above the normal level. Twelve burn patients with total body surface area burns ranging from 32% to 87% were studied. At various postburn times, neutrophils were isolated and their ability to kill Staphylococcus aureus in the presence and absence of glutamine was determined and compared with that in normal subjects. Glutamine enhanced the bactericidal function of normal neutrophils. In every patient, at all but two postburn times, glutamine caused an improvement in the observed abnormal neutrophil bactericidal function and often restored it to or slightly above the normal level. Glutamine had no effect on the expression of C3b receptors (CR1 or CD35) or on phagocytosis by the cells. This study confirms the beneficial effects of glutamine in at least one arm of the immune system and adds evidence for the possible advantage of including this amino acid in the diets of burn and other trauma patients. PMID- 8201748 TI - Kinetics of medium-chain triglycerides and free fatty acids in healthy volunteers and surgically stressed patients. AB - To determine the hydrolysis rate of medium-chain triglycerides (MCTs) to medium chain free fatty acids (MCFAs) and the disposition rate of MCFAs, five healthy volunteers (H) and eight surgically stressed patients (S) received 0.5 mL of Lipofundin 20% per kilogram body weight as an intravenous bolus. Serum MCTs (C8 and C10) and MCFAs were measured by high-performance liquid chromatography during the 120 minutes postinjection. A linear two-compartment model was found to be descriptive and robust: the apparent volumes of distribution were found to be similar in healthy and surgical subjects for both MCTs and MCFAs. The first-order transformation rate constant (hydrolysis) from MCTs to MCFAs was not significantly different between the H and S groups (overall 0.112 +/- 0.022/min, C8; 0.078 +/- 0.020/min, C10). The rate constant for tissue MCFA uptake from plasma was significantly different between S and H subjects both for C10 alone (H: 0.0337 +/- 0.0078; S: 0.1194 +/- 0.0240; p = .020) and for C8 and C10 together (H: 0.0382 +/- 0.0054; S: 0.1012 +/- 0.0168; p = .008), whereas it failed to attain significance when C8 alone was considered (H: 0.047 +/- 0.0077; S: 0.0829 +/- 0.0230; p = .210). These results show that use of MCTs is increased in surgical patients because of enhanced tissue uptake of the corresponding free fatty acids, whereas there does not seem to be an increase of MCT hydrolysis in response to acute disease. This would indicate that the stressed patient is in fact able to effectively use this alternative lipid substrate in the face of increased metabolic demand. PMID- 8201749 TI - Alteration of mucosal immunity after long-term ingestion of an elemental diet in rats. AB - The effects of an elemental diet on lymphocyte transport in intestinal lymph and immune responses of gut-associated lymphoid tissue were investigated in rats. The control animals were fed a conventional diet. After 4 week of feeding, the total calorie intake and body weight gain showed no differences between the two groups. The number and total area of Peyer's patches and the ratio of height of villi to height of crypt showed no significant differences between the two groups. The rate of lymph flow in intestinal lymphatics showed no significant change in treated animals compared with the control rats. However, an elemental diet induced a significant decrease in lymphocyte flux in intestinal lymphatics compared with that in control rats. Lymphocyte subsets in intestinal lymph revealed a significant decrease in CD3-positive cells, especially CD4-positive cells in the elemental diet-treated group. A significant decrease in the number of immunoglobulin A-containing cells and a decreased CD4/CD8 ratio in T-cell subsets were observed in the lamina propria of ileal mucosa in the elemental diet treated group by morphometric analysis in the immunohistochemical study. Specific antibody-secreting cells in intestinal lymph were also investigated after rats were intraduodenally primed with cholera toxin and challenged with the same toxin after an interval of 2 weeks. No significant difference was seen between the two groups in any of the numbers of anti-cholera toxin immunoglobulin-secreting cells in any immunoglobulin A, immunoglobulin G, or immunoglobulin M class as determined by the enzyme-linked immunospot assay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201750 TI - Parenteral vs enteral nutrition in tumor-bearing rats. AB - The development of cachexia may complicate cancer therapy, yet controversy exists concerning its nutritional management. For example, use of total parenteral nutrition (TPN) may not be appropriate because of gut atrophy, possible stimulation of tumor growth, and lack of total host protein repletion. In the present experiment, host and tumor responses were compared after identical parenteral or enteral nutritional supplementation (EN). Eighteen days after subcutaneous inoculation of adult male Fischer-344 rats with fresh methylcholanthrene-induced sarcoma (tumor-bearing [TB] rats), catheters were placed into either the external jugular vein or the stomach. Four days later, rats were started on an 11-day course of either TPN or EN with a Freamine-III based formula (amino acids = 6%, dextrose = 21.5%, lipid = 1.5%). When the rats were killed, there was no difference in tumor weight between the various TB groups. Carcass weight was increased significantly in both the TB-TPN and TB-EN groups, and there was an elevation in gastrocnemius protein content in both groups compared with the TB-rat food group. Small intestine protein was preserved in the TB-EN group to the level observed in the control-rat food animals. Total lipids in the liver were increased in both TB-TPN and TB-EN groups; however, the magnitude of the increase was less in the TB-EN animals. Neither treatment resulted in complete protein repletion of tumor-bearing rats. EN may be more appropriate than TPN in that gut mass is preserved. The maintenance of gut mucosa may prove to be beneficial in the treatment of the depleted, immunocompromised, and metabolically stressed host. PMID- 8201751 TI - A randomized study of a pH sensor feeding tube vs a standard feeding tube in patients requiring enteral nutrition. AB - Postpyloric feedings are a widely practiced form of enteral nutrition. We prospectively randomized two groups of hospital patients to receive a standard feeding tube or a feeding tube that uses a pH sensor to facilitate postpyloric placement and compared placement speed and accuracy, displacement detection, and costs for the two groups. Thirty-nine patients were randomized, with 20 receiving a pH sensor feeding tube and 19 an identical non-pH sensor feeding tube. An x-ray of the kidneys, ureter, and bladder was taken at 1, 6, and 48 hours after placement in both groups. Separate cost-benefit analyses were done by using retrospective chart review of costs for a separate 20-patient standard feeding tube group and calculated costs for a 20-patient hypothetical pH sensor group. At 1 hour, the duodenum was reached in 53% of the pH sensor feeding tube patients and 45% of the standard feeding tube patients (the difference was not significant). At 48 hours, 93% of the pH sensor feeding tubes reached the duodenum vs 67% of the standard feeding tubes (p < .08). Thirty percent of the pH sensor patients had an initial gastric pH > or = 4, negating pH sensor benefit in tube placement. In the remaining 70% of the patients, placement with the pH sensor had a 100% specificity compared with the x-ray of the kidneys, ureter, and bladder. Displacement was easily detected with routine pH monitoring in three of the pH sensor feeding tube patients and corrected. It was detected in two standard feeding tube patients, one of whom aspirated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201752 TI - The modulatory role of gut hormones in elemental diet and intravenous total parenteral nutrition-induced bacterial translocation in rats. AB - We have previously shown that parenteral and certain elemental diets promote bacterial translocation and that this diet-induced bacterial translocation can be prevented by the provision of bulk-forming dietary fiber. The goal of the current study was to test the hypothesis that fiber's protective effect on diet-induced bacterial translocation was mediated by trophic gut hormones. This hypothesis was tested by using bombesin (which stimulates gut hormone release) or the somatostatin analog Sandostatin (which inhibits gut hormone release) to modulate gut hormone release in rats receiving rat food, intravenous total parenteral nutrition, or an elemental diet. Both bombesin and fiber were effective in preventing elemental diet-induced bacterial translocation, whereas octreotide acetate abrogated the protective effect of fiber. Bombesin was also effective in limiting bacterial translocation in parenterally fed rats. Although both enteral (elemental diet) and parenteral diet-induced bacterial translocation were associated with cecal bacterial overgrowth, loss of small-bowel weight, and loss of mucosal protein content, none of these factors seemed to be primarily responsible for bacterial translocation. Because bombesin decreased the incidence of villous injury in the elemental diet-fed rats and decreased the incidence of villous injury and prevented loss of intestinal barrier function to horseradish peroxidase in the parenterally fed rats, it is possible that bombesin exerted its protective effect by limiting mucosal injury and preserving barrier function. PMID- 8201754 TI - Assessing the validity of adjusted urinary urea nitrogen as an estimate of total urinary nitrogen in three pediatric populations. AB - Nitrogen excretion is a useful measurement for determining efficiency of protein utilization. Knowledge of nitrogen losses is especially important in the treatment of stressed, postsurgical, or catabolic patients, in whom optimizing the amount of nitrogen intake in the diet may spare visceral and somatic proteins and encourage anabolism. Many methods have been used to estimate total urinary nitrogen (TUN) in different patient populations. Urinary urea nitrogen (UUN) values are routinely adjusted and used by investigators who are not able to measure TUN directly by either Kjeldahl or pyrochemoluminescent methods. The rationale for the use of adjusted UUN concentrations to predict TUN is based on adult experiences. No similar experience in pediatrics has been published. We have compared TUN with adjusted UUN in a study of 250 urine samples from pediatric patients (n = 34) and normal pediatric volunteers (n = 109). Our findings suggest that adjusted UUN (determined by previously established formulas) may be of limited use in estimating TUN in neonates, infants, and critically ill pediatric patients; however, adjusted UUN may be useful in approximating TUN in healthy school-aged children. Good correlations were found between UUN and TUN for critically ill children and postsurgical neonates and infants, suggesting that these newly described regression equations (once validated) may be useful in predicting TUN from a measured UUN. PMID- 8201753 TI - Glutamine-supplemented parenteral nutrition improves gut mucosa integrity and function in endotoxemic rats. AB - The effects of glutamine-supplemented parenteral nutrition on protein metabolism, small intestinal mucosal metabolism, morphology, and barrier function were studied in endotoxin-treated rats. Forty-six male Wistar rats were randomized to two groups of 23 animals each and received total parenteral nutrition solutions supplemented with either glutamine (GLN group) or glycine (GLY group) at 2% wt/vol. Endotoxemia was induced by continuous intravenous infusion of endotoxin at a dose of 2 mg/kg per day throughout the 4-day study period. The GLN group had a less-negative cumulative nitrogen balance (-14.0 +/- 132.8 mg of nitrogen in the GLN group and -86.8 +/- 161.7 mg of nitrogen in the GLY group, p < .05) and less cumulative excretion of urinary 3-methylhistidine (2910 +/- 593 nmol) than the GLY group (4447 +/- 933 nmol, p < .01). Jejunal mucosal glutaminase activity and the arterio-portal venous blood glutamine concentration differences were significantly higher in the GLN group compared with the GLY group (15.6 +/- 2.3 vs 11.1 +/- 1.9 mumol/g per minute, p < .05, and 181 +/- 52 vs 147 +/- 36 nmol/mL, p < .05, respectively). The morphology of the jejunal mucosa in the GLN group was significant for having greater mucosal weight (23.4 +/- 3.1 vs 17.6 +/- 2.5 mg/cm), villus height (445 +/- 75 vs 357 +/- 57 microns), crypt depth (197 +/ 34 vs 161 +/- 28 microns), and wall thickness (751 +/- 77 vs 648 +/- 102 microns) than the GLY group (p < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201755 TI - Central line occlusion with three-in-one nutrition admixtures administered at home. AB - The use of single-container parenteral nutrition admixtures can be cost effective and can simplify home administration. Three-in-one admixtures (dextrose, amino acids, lipid emulsion, and other additives in a single bag) were in use when a marked increase in catheter occlusions was seen in the pediatric home parenteral nutrition population. Insoluble laminar deposits were found in the removed catheters. In all subsequently placed catheters, separate (SPLIT) infusions of lipid and parenteral nutrition solution were used rather than three-in-one admixtures. This was associated with an obvious decrease in catheter occlusions. Catheter life-span was retrospectively determined for 15 catheters of identical size and style that were used in eight patients who had received either infusions of three-in-one admixtures or SPLIT infusions. Life table survival analysis revealed a median survival time of 70 days for the three-in-one group (n = 8) and 290 days for the SPLIT group (n = 7). Survival distributions for the two groups were significantly different (p = .025). During the period of clustered catheter occlusion, the use of three-in-one admixtures that were stored in the home for up to 7 days was associated with a shortened catheter life-span. Occlusion or deposit development was not seen in catheters used for inpatient parenteral nutrition support when admixtures were prepared and infused within 28 hours. Catheter deposits were implicated as sanctuary sites for pathogenic bacteria in two patients. Failure to retrieve and inspect occluded catheters delayed the identification of the deposits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201756 TI - Enteral supplementation of phosphate does not prevent hypophosphatemia during refeeding of cachectic patients. AB - Hypophosphatemia due to parenteral nutrition has been described frequently. It was attributed to the lack of phosphorus content in parenteral nutrition solutions. With modern parenteral nutrition regimens containing phosphorus, this problem has been virtually eliminated. Enteral nutrition solutions contain adequate phosphate for patients with normal phosphate stores. Hypophosphatemia has therefore rarely been reported in enteral nutrition. We describe two patients with protein-energy malnutrition who developed severe hypophosphatemia during tube feeding with phosphorus-containing formula diets. Chronic alcoholism and vitamin D deficiency due to malabsorption because of Crohn's disease were additional risk factors in these two patients. Patients with depleted phosphate stores and high metabolic demand have a higher daily requirement for phosphorus than is available in routine isotonic enteral formulas. This case report emphasizes the importance of monitoring serum phosphate concentration daily during the first week of refeeding. PMID- 8201757 TI - Anemia and neutropenia due to copper deficiency in enteral nutrition. AB - Copper deficiency has been regarded a rare complication of total parenteral nutrition. This report describes the first known case of anemia and neutropenia caused by copper deficiency in a patient receiving long-term enteral nutrition. A 34-year-old man presented with bulbar palsy and tetraplegia after an operation for cerebellar hemorrhage on June 7, 1989. Nasopharyngeal tube feeding with a defined-formula diet (Besvion) was instituted on June 19, 1989. He developed normocytic anemia and neutropenia approximately 19 months after the initiation of the tube feeding. Serum copper and ceruloplasmin levels were markedly below normal. There were anisocytosis and erythrocyte deformities in the peripheral blood smear. Bone marrow aspirates revealed a hypocellular marrow with numerous myeloid and erythroid cells with cytoplasmic vacuoles. Because the amount of copper administered was estimated to be 2.6 to 5.1 mumol/d during the tube feeding, copper deficiency was suspected to be the cause of the hematologic disorders. The patient's daily oral copper intake was increased to 34 mumol/d. His serum copper and ceruloplasmin concentrations reached a normal level after 16 days and 23 days of copper supplementation, respectively. A marked reticulocytosis occurred after 10 days of copper supplementation, and his anemia gradually improved over the next 3 months. His blood neutrophil count also returned to normal within 2 weeks. PMID- 8201758 TI - Copper deficiency with pancytopenia during total parenteral nutrition. AB - Anemia and neutropenia are commonly observed hematologic changes in patients with copper (Cu) deficiency, but thrombocytopenia is rarely found. A-69-year-old patient with postoperative small-bowel obstruction underwent laparotomy three times. Because of persistent obstruction, nasoduodenal suction was continued and total parenteral nutrition was instituted. Fifteen months after the initiation of total parenteral nutrition, the patient gradually developed pancytopenia (red blood cell count 222 x 10(4)/mm3, neutrophil count 1254/mm3, and platelet count 9.2 x 10(4)/mm3). The serum Cu level was 10 micrograms/dL and the serum ceruloplasmin level was less than 5 mg/dL. After 2 weeks of Cu supplementation in a daily dose of 20 mumol, the serum Cu level increased to 81 micrograms/dL and the serum ceruloplasmin level to 20 mg/dL. Hematologic values showed a dramatic response: red blood cell count increased to 362 x 10(4)/mm3, neutrophil count to 4819/mm3, and platelet count to 22.1 x 10(4)/mm3. The improvement of pancytopenia could be attributed to Cu supplementation. This is the first case report of Cu deficiency with pancytopenia during total parenteral nutrition. PMID- 8201759 TI - A practical equation to predict resting metabolic rate in older men. PMID- 8201760 TI - Arginine stimulates wound healing and immune function in elderly human beings. PMID- 8201761 TI - Body composition: research and clinical advances--1993 A.S.P.E.N. research workshop. AB - The 1993 ASPEN Research Workshop examined research and clinical advances in the study of human body composition. The workshop had two themes: (1) compartments of the body and their measurement, and (2) clinical applications of body composition measurements. There were 12 speakers of varied backgrounds who gave short lectures followed by panel discussions. Speakers explored the validity and potential uses of new body composition methodologies, including dual-energy x-ray absorptiometry, multiple frequency bioimpedance analysis, computerized axial tomography, magnetic resonance imaging, nuclear magnetic resonance spectroscopy, neutron inelastic scattering, and gamma-ray resonance. The application of these methods to chronically and acutely ill hospitalized patients was described. The study of body composition is an emerging distinct research area within the broad study of human biology. This conference provided an overview of important new advances in the study of human body composition. PMID- 8201762 TI - [[New antimicrobial agent series XLVII]: levofloxacin]. PMID- 8201763 TI - [Cefazolin sodium]. PMID- 8201764 TI - [Vancomycin hydrochloride]. PMID- 8201765 TI - [Cefotiam hydrochloride]. PMID- 8201766 TI - [Drug resistance and phage typing of clinical isolates of Staphylococcus aureus]. AB - Activities of antimicrobial agents were examined against Staphylococcus aureus strains isolated in 1990. Strains resistant to benzylpenicillin were isolated at the highest frequency (93.6%), and followed by those resistant to kanamycin (51.5%), erythromycin (49.0%), gentamicin (45.1%), fluoroquinolone (33.4%) and minocycline (12.3%). Most of these drug resistant strains of S. aureus were also resistant to methicillin. It should be noted that the MRSA strains were also resistant to other multiple drugs. Annual changes of MRSA in clinical isolates have been increasing since 1981. The isolation frequencies of MRSA strains were 18.9%, 44.8% in 1981 and 1990, respectively. Among methicillin susceptible S. aureus (MSSA), however, drug resistance to other antibiotics have been decreasing year by year. Many strains among both MRSA (73%) and MSSA (86%) were sensitive to typing phages of 100 x RTD. 76% of the MRSA strains were phage typed into groups III or mixed, and 60% of the MSSA strains were typed into these two groups, also. PMID- 8201767 TI - [Antimicrobial activities of cefuroxime against recent clinical isolates]. AB - Antimicrobial activity of cefuroxime axetil (CXM-AX) was compared with those of other cephem antibiotics against clinically isolated strains obtained mainly from outpatients of our center in a period from January to September of 1990 and 1993. Minimum inhibitory concentrations were determined and the following results were obtained. 1. The results suggested that, compared with reports of studies conducted with clinical isolates in early 1980's, MIC80 of CXM were equal to or lower against Staphylococcus spp., Streptococcus pyogenes, Escherichia coli, Klebsiella spp., Proteus mirabilis, Haemophilus influenzae, Moraxella subgenus Branhamella catarrhalis, Neisseria gonorrhoeae, Peptostreptococcus spp., and Propionibacterium acnes, except for Streptococcus pneumoniae, MIC80 which was slightly higher. 2. MIC90 of comparator drugs reflected those of new resistant organisms recently appeared, such as benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP), cephem-resistant E. coli and Klebsiella spp., new quinolone resistant H. influenzae and N. gonorrhoeae. Methicillin-resistant Staphylococcus aureus (MRSA) was detected also from specimens of community acquired infections. From the nature of MRSA detected in those situations MRSA appeared to present a continuing problem. 3. MIC90 against strains obtained from patients with community acquired infections was a good index of increases of multidrug resistant organisms in the past. Therefore, the determination of MIC90 is important in examining changes with time of sensitivities or resistances of clinically isolated strains to antimicrobial drugs. 4. Antimicrobial activities of CXM against recent clinical isolates showed the existence of problems as mentioned above. However, MIC of CXM as well as those of comparator drugs indicated that antimicrobial activities of CXM against Staphylococcus spp., Streptococcus spp., H. influenzae appeared to be relatively strong, and it is concluded that cefuroxime axetil still is one of the clinically useful oral antimicrobial drugs in the 1990's. PMID- 8201768 TI - [Pharmacokinetic and clinical studies of SY5555 in the pediatric field. Pediatric Study Group of SY5555]. AB - SY5555, a new oral penem, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained: 1. Pharmacokinetics Pharmacokinetics of SY5555 dry syrup (powder which is dissolved before use) was investigated in 64 children. At a dose level of 3 mg (potency)/kg, Cmax and T1/2 were 0.33 micrograms/ml and 0.95 hours (n = 1), respectively, in the non-fasting state. At a dose level of 5 mg/kg Cmax and T1/2 were 2.09 +/- 1.25 micrograms/ml and 1.20 +/- 1.07 hours, respectively, in the fasting state, and were 1.21 +/- 0.70 micrograms/ml and 1.33 +/- 0.90 hours, respectively, in the non-fasting state. At a dose level of 10 mg/kg, Cmax and T1/2 were 2.96 +/- 1.89 micrograms/ml and 0.89 +/- 0.43 hours, respectively, in the fasting state, and were 2.45 +/- 1.37 micrograms/ml and 1.17 +/- 0.53 hours, respectively, in the non-fasting state. At a dose level of 15 mg/kg, Cmax and T1/2 were 4.30 +/- 2.15 micrograms/ml and 0.82 +/- 0.09 hours, respectively, in the non-fasting state. Data of Cmax and AUC showed that plasma concentration of the drug depended on dose levels. Urinary recovery rates in the first 6 hours were 1.71% (n = 1) in the non-fasting state at a dose level of 3 mg/kg, 4.13 +/- 1.40% in the fasting state and 4.17 +/- 3.29% in the fasting and the non-fasting state, respectively at a dose level of 5 mg/kg, and 6.02% (n = 1) and 4.64 +/- 2.81%, respectively, at a dose level of 10 mg/kg. At a dose level of 15 mg/kg, urinary recovery rate in the first 6 hours was 7.97% (n = 2) in the non-fasting state. 2. Clinical results 1) Dry syrup The clinical efficacy of the SY5555 dry syrup was evaluated in 506 cases. SY5555 was administered at daily doses of 15-30 mg/kg divided into 3 equal doses to most patients. Daily doses of 12- < 18 mg/kg were given to 46.6% of the patients. The overall clinical efficacy rate was 92.9%, and this drug was effective in 93.0% of the 301 patients for whom the causative pathogens were identified, and in 92.7% of the 205 patients with infections for whom the causative pathogens were unknown. The efficacy rate at daily doses of 12 - < 18 mg/kg was 94.5% similar to those obtained at daily doses of 18- < 27 mg/kg (91.7%) or 27- < 33 mg/kg (91.3%). The bacteriological eradication rate was 82.3%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201769 TI - [Basic and clinical studies on cefditoren pivoxil in pediatric field]. AB - Cefditoren pivoxil (CDTR-PI, ME1207) granules, a new oral cephem, was given to pediatric patients with infectious diseases to evaluate antibacterial activities against clinical isolates, pharmacokinetics, clinical efficacy and safety, and the following results were obtained. 1. In sensitivity test, 30 strains were used comprised of 5 species, isolated from the patients before administered with CDTR PI. Against Staphylococcus aureus, MICs of 7 agents, cefditoren (CDTR), cefaclor, cefixime, cefteram, cefotiam, cefpodoxime and methicillin, were determined. Against other 4 species, MICs of the above 6 agents excluding methicillin were determined. Among Gram-positive cocci tested, the MICs of CDTR were 0.78 to 100 micrograms/ml or higher against S. aureus (16 strains), < or = 0.025 microgram/ml against Streptococcus pyogenes (5 strains), and 0.10 or 0.39 microgram/ml against Streptococcus pneumoniae (2 strains). These values were equal to or lower than those of conventional cephems and of methicillin. Among Gram-negative rods tested, the MICs of CDTR were < or = 0.025 microgram/ml against Haemophilus influenzae (3 strains), and 0.10 or 0.20 microgram/ml against Escherichia coli (4 strains). Also, these values were equal to or lower than those of conventional cephems. 2. When CDTR-PI granules was orally administered in a single dose of 3.0 mg/kg to 1 patient and that of 6.0 mg/kg to 2 patients 30 minutes after meal, plasma CDTR concentrations reached their maxima 4 hours after administration in the former patient and 1 or 2 hours after administration in the latter 2 patients, and the peak plasma concentrations were 1.91, 3.46 and 4.82 micrograms/ml with half-lives of 1.01, 0.81 and 0.88 hours and AUCs of 8.62, 9.89 and 13.52 micrograms.hr/ml, respectively. Dose-dependency was observed for the peak plasma concentrations and AUCs also tended to depend on dose excepting for the AUC in one 6.0 mg/kg patient. 3. The urinary concentrations in the above patients reached their peaks at 4 to 6 hours after administration in one 3.0 mg/kg patient and at 4 to 6 hours and 2 to 4 hours after administration in two 6.0 mg/kg patients, and the corresponding values were 126.0, 195.0 and 234.0 micrograms/ml, respectively. Recovery rates in the first 8 hours after administration were 18.2, 24.6 and 21.3%, respectively. 4. Of 53 patients with 13 diseases, CDTR-PI was clinically judged "excellent" in 32 (60.4%) and "good" in 21 (39.6%), showing excellent efficacy. 5. Bacteriologically, excellent results were obtained, i.e., 29 (96.7%) of 30 strains from 5 species were eradicated. 6. Side effects were observed in none of the 54 patients treated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8201771 TI - [Differentiation of macrophages]. PMID- 8201770 TI - [Mechanism on the production of Clostridium difficile toxins]. PMID- 8201772 TI - [The role of flagella of Campylobacter jejuni in colonization in the intestinal tract in mice and the cultured-cell infectivity]. AB - For analyzing the role of the bacterial flagella in colonization in the intestinal tract of mice and adhering to or invading the Intestine 407 cell, a nonflagellated, nonmotile mutant was induced by ultraviolet irradiation of a flagellated, motile wild-type strain of Campylobacter jejuni CF84-340. There was no great difference in the cellular infectivity to the Intestine 407 cells between the wild-type and the mutant strains. Cellular adherence and invasiveness were then compared by fluorescent antibody staining, and an obvious difference was found in the latter. While 21.4% of the organisms of the wied-type strain invaded the cells, only 6.1% of those of the flagella-defective mutant did so. In the experiments in mice involving oral administration, cellular invasiveness was not found with the flagella-defective mutant and no organisms were detected from the blood, although bacteremia is one of the characteristics of infection with C. jejuni. Moreover, no intestinal adherence of the mutant was detected, suggesting early elimination of the organism administered. These results indicate that the bacterial flagella are concerned in not only the cellular adherence and intestinal deposit, but also the intracellular invasiveness and invasion into the blood stream from the intestinal wall in the infected mice. PMID- 8201773 TI - Evidence for slow conduction areas during pacing in patients with sinus rhythm, and their relation to the site of VT origin. AB - In 52 patients with reentrant monomorphic sustained ventricular tachycardia (VT), the site of VT origin was determined by endocardial mapping and the interval from stimulus artifact to the onset of QRS complex (St-QRS) was measured during pace mapping. Eleven patients had remote myocardial infarction (group 1), 25 patients had other underlying heart diseases (group 2), and 16 had idiopathic VT (group 3). At St-QRS interval of 40 msec or longer was defined as abnormal. (1) Long St QRS interval: Thirteen sites with long St-QRS intervals were detected in 13 (25.0%) of 52 patients: 5 patients in group 1 (45.5%), 7 (28.0%) patients in group 2 and one (6.3%) in group 3. (2) Local electrogram: The local electrogram at sites with a long St-QRS interval was wide and 113 +/- 38 msec in duration during sinus rhythm which increased to 159 +/- 64 msec during VT (p < 0.05). In sinus rhythm, an abnormally prolonged local electrogram was observed in 11 of 13 sites with a long St-QRS interval, and mid-diastolic potential or continuous activity was observed in 3 sites during VT. (3) Relation to VT origin: At sites with a long St-QRS interval, concealed entrainment was observed in 3 patients, and the earliest activated local electrogram during VT in 5 patients. CONCLUSION: Sites with a long ST-QRS interval were observed in 25% of the patients with VT, and their incidence tended to be higher in patients with ischemic heart disease. Such sites were associated with abnormal local electrograms and some of the sites were considered to be the active limb of the reentry circuit. PMID- 8201774 TI - Infected right atrial thrombus and pulmonary emboli associated with a perforated jejunal diverticulitis. AB - We describe a patient with an infected right atrial thrombus and pulmonary embolism who died suddenly. Jejunal diverticulitis, which was found at autopsy, was suspected to be the source of the bacterial thrombus. The 41-year-old female patient was admitted because of dyspnea and syncopal attacks. Physical examination on admission revealed an obese woman with a body temperature of 36.5 degrees C, systolic heart murmur and abnormal diastolic heart sound. Two dimensional echocardiography revealed a strand-shaped mass in the right atrium. Lung blood perfusion scintigraphy revealed multiple perfusion defects in both lung fields. She suddenly developed severe dyspnea leading to death on the 6th hospital day. At autopsy, a strand-shaped organized thrombus was found in the right cardiac chambers. Microscopically, the thrombus was found to be infiltrated with numerous gram-positive cocci, leukocytes and a small number of gram-negative cocci. Most of the major pulmonary arterial branches were occluded by bacterial thromboemboli, and multiple pulmonary infarctions were found in both lungs. A perforating diverticulum with microabscess was found in the jejunal mucosa which was assumed to be the source of the bacterial thromboembolism. PMID- 8201775 TI - Malignant lymphoma presenting as a cardiac tumor. AB - We report a case of malignant lymphoma whose initial symptoms were heart failure. An echocardiogram showed a large tumor in the right ventricle, and a definitive diagnosis was obtained at autopsy. Of particular interest in our case, the lymphoma was confined to the heart and a mediastinal lymph node, with its greatest bulk being intracardiac. This case is a rare manifestation of malignant lymphoma. PMID- 8201776 TI - Cardiac pheochromocytoma. A case report and review of the literature. AB - A case of intrapericardial pheochromocytoma which secreted predominantly norepinephrine is reported. A tumor at the posterior wall of the left atrium was demonstrated by computed tomographic and magnetic resonance imaging scan. Tumor blush arising from the left circumflex branch was visualized by coronary angiography. The tumor (4 x 3.5 x 2 cm) was resected with adherent atrial wall and the defect reconstructed with the patients own pericardium under general anesthesia with artificial cardiopulmonary bypass. His subsequent postoperative recovery was uneventful. At the time of discharge, 8 weeks after operation, his blood pressure and plasma norepinephrine remained normal. The value of magnetic resonance imaging scan for the topographic diagnosis of cardiac pheochromocytoma is emphasized. PMID- 8201777 TI - Importance of total leg muscle mass for exercise intolerance in chronic heart failure. AB - Patients with chronic heart failure symptoms tend to avoid voluntary effort and are thus subject to physical deconditioning. The presence of symptoms in daily life is thought to predispose to physical deconditioning and subsequent skeletal muscle loss. This study was designed to describe the relation among daily physical activities, skeletal muscle loss and exercise capacity in patients with chronic heart failure. We studied 14 patients with severe cardiac dysfunction (left ventricular ejection fraction < 40%) and 7 age-matched normal subjects. We measured total leg muscle mass by dual energy X-ray absorptiometry. The patients were divided into 7 asymptomatic and 7 symptomatic individuals using questionnaires for specific physical activities. Peak oxygen uptake and anaerobic threshold were significantly reduced in cardiac patients as compared with normal subjects. The reduction in exercise capacity was greater in the symptomatic patients than in asymptomatic patients. Leg muscle mass was significantly reduced (-17%) in the symptomatic patients, while it remained normal in the asymptomatic patients. Oxygen uptake in unit muscle mass at the level of anaerobic threshold and at peak exercise was decreased in both the asymptomatic (-21% and -21%, respectively) and symptomatic patients (-27% and -30%, respectively) but the difference between these two groups was not significant. In the asymptomatic patients, the reduced exercise capacity was accounted for primarily by muscle mass-independent factors such as an impaired nutritive blood flow to exercising muscles or metabolic abnormalities within the muscle cell. In the symptomatic patients, the marked reduction in exercise tolerance was attributable to a decrease in leg muscle mass and to hemodynamic or metabolic abnormalities. We conclude that the loss of leg muscle mass plays an important role in exercise intolerance in patients who are prone to physical deconditioning as a result of symptomatic heart failure. PMID- 8201778 TI - Reduction of beta-adrenergic receptors in atrial cell membranes of patients following mild to moderate heart failure. AB - The density of cardiac beta-adrenoceptors (Bmax) was measured in eighteen patients [2 with atrial septal defect (ostium secundum), 4 with aortic valve disease, 3 with mitral valve disease, 1 with aortic and mitral valve disease, 5 with a history of myocardial infarction, and 3 with angina pectoris] following mild to moderate cardiac failure. Measures were obtained by cardiac catheterization prior to cardiac surgery and also during the surgical procedures. On the basis of symptoms immediately preceding surgery, the severity of the condition in each patient was categorized as either Class I (n = 5) or Class II (n = 13) following the New York Heart Association (NYHA) functional classification system. The Bmax was measured using right atrial appendage tissue obtained during cardiac surgery. [125I]-iodocyanopindolol was used for the assay. The Bmax of atrial cell membranes in patients with NYHA class II was significantly lower than that of class I (34.1 +/- 2.5 vs 55.4 +/- 9.3 fmol/mg protein, M +/- SE, p < 0.05). Correlation coefficients between the Bmax and hemodynamic parameters measured just prior to cardiac surgery were examined, but only that between Bmax and the minimum value of the time derivative of left ventricular pressure (max negative dp/dt) was significant (r = -0.552, p < 0.05). Further study is needed to understand and clarify the relationship between Bmax and dp/dt min. PMID- 8201779 TI - Postprandial hemodynamic changes evaluated by a Doppler echocardiographic method. AB - To evaluate postprandial hemodynamic changes, Doppler measurements of stroke volume before and after lunch were carried out in 10 healthy volunteers (all men) with a mean age of 28 years. The stroke volume was calculated as the product of echocardiographically determined aortic valve area and the ejection flow velocity integral obtained by continuous wave Doppler. The stroke volume before lunch was 61 +/- 7 ml, which was increased to 72 +/- 8 ml 1 hour after lunch and remained constant for the next 4 hours. Five hours later the stroke volume was then decreased to the baseline. M-mode echocardiography revealed an increase in left ventricular end-diastolic dimension and ejection fraction after lunch. Another 9 healthy subjects (6 women and 3 men) with a mean age of 52 years received a 75 g oral glucose tolerance test (OGTT) instead of a common lunch; stroke volumes were not altered in association with the elevation of plasma glucose level. In conclusion, ingestion of food had a positive inotropic effect and caused circulating blood volume expansion with an increment of heart rate. Therefore, Doppler studies that are not standardized for patients' mealtimes may affect the validity of data in serial studies of left ventricular function. PMID- 8201780 TI - Partial anomalous pulmonary venous return. Evaluation of 51 cases. AB - Partial anomalous pulmonary venous return (PAPVR) is a congenital anomaly in which one or more, but not all, of the pulmonary veins are connected to a systemic vein or to the right atrium directly. Its incidence is higher in autopsy series than in clinical series. We report 51 cases of PAPVR diagnosed by cardiac catheterization and evaluated from the aspects of age, sex, type and associated anomalies and diseases. PMID- 8201781 TI - Pharmacokinetics of propranolol used for suppressing tachycardia in hyperthyroidism. AB - The aim of this study was to investigate the pharmacokinetics of propranolol in patients with hyperthyroidism, and its effect on heart rate (HR) using 24 hour ECG monitoring. Subjects included 9 patients with hyperthyroidism (group H) and 9 euthyroid patients with hypertension selected as the control group (group C). All patients took propranolol at a dosage of 10 mg, 3 times a day for 7 days. Plasma propranolol concentrations were measured on the 7th day of its administration by the HPLC method. Twenty-four hour-ECG monitoring was recorded twice before and after treatment with propranolol. The mean reduction in the minimum HR was 10.7 +/- 3.6 (11.9 +/- 3.6%) in group H and 5.0 +/- 1.6 (9.5 +/- 3.0%) bpm in group C. That in the average HR was 12.2 +/- 3.7 (11.3 +/- 3.1%) in group H and 9.2 +/- 2.2 bpm (13.7 +/- 3.2%) in group C. That in the maximum HR was 16.9 +/- 5.2 (10.9 +/- 3.1%) in group H and 24.4 +/- 2.4 bpm (21.9 +/- 2.1%) in group C. The peak concentration of propranolol in plasma was 10.8 +/- 2.4 ng/ml in group H and 55.3 +/- 14.3 ng/ml in group C (p < 0.01). There was a linear correlation between the reduction in the hourly maximum heart rate and the peak plasma propranolol concentration in group H. Cardiovascular manifestations in hyperthyroid patients were related to sympathetic hypersensitivity and their improvement was not fully obtained by small doses of propranolol. PMID- 8201782 TI - Effects of vesnarinone (OPC-8212) on Ca(2+)-activated K channels and cytosolic Ca2+ in cultured smooth muscle cells from porcine coronary artery. AB - Vesnarinone is a new, non vasodilating cardiotonic agent. This study compared the effects of vesnarinone and amrinone, a phosphodiesterase (PDE) inhibitors with vasodilating actions, on cultured smooth muscle cells from the porcine coronary artery. Application of vesnarinone (10(-4) M) or amrinone (10(-4) M) to the bath solution in cell-attached patches activated the KCa channel having a conductance of 133 pS (bath 2.7 mM K, pipette 140 mM K). Application of vesnarinone to the cytosolic side had no direct effect on KCa channel activities in inside-out patches. Activation of the KCa channel was suppressed when the intracellular production of cAMP was suppressed by preincubation with carbachol (10(-6) M). Amrinone, but not vesnarinone, lowered [Ca2+]i in the K(+)-depolarized smooth muscle cells (K+ = 70 mM). These results suggest that vesnarinone exerts an additional effect on [Ca2+]i that is independent of PDE inhibition. The difference in the effects on [Ca2+]i in vascular smooth muscle cells may explain in part the differing actions of these agents on vascular relaxation. PMID- 8201783 TI - Stroke volume with dynamic cardiomyoplasty during ventricular fibrillation in the acute dog. AB - The objective of this study was to determine the pumping capability of dynamic cardiomyoplasty during induced ventricular fibrillation. In this acute study of 6 dogs, the pumping capability of the unconditioned left latissimus dorsi (LD) muscle (141 to 292 gm), wrapped around both ventricles, was investigated during induced ventricular fibrillation. Left-ventricular and femoral artery pressure, the ECG and aortic root flow velocity were monitored. Prior to inducing ventricular fibrillation, the ability of the unconditioned LD muscle to augment stroke volume (SV), was quantified as the area under the aortic flow-velocity record. The ventricles were then fibrillated and, after 10 sec, rhythmic 250 msec trains (1/sec) of stimuli (40/sec) were delivered to the thoracodorsal nerve to contract the LD muscle tetanically. In no case could dynamic cardiomyoplasty produce the same SV as when the ventricles were beating normally. In one animal, the SV attained two percent of the normal SV by 5 contractions; in another, the SV reached one percent by 25 contractions. In the remaining animals, the SV varied around 20% of the prefibrillation SV. By 90 contractions, the stroke volume was 10% of the prefibrillation value. The progressive decrease in SV was likely a consequence of LD muscle ischemia and fatigue, since the latissimus dorsi muscle provided low blood flow during the period of fibrillation. PMID- 8201784 TI - A case of myocardial infarction showing extensive precordial ST elevation induced by second diagonal branch occlusion. AB - We observed a case of acute myocardial infarction induced by second diagonal branch occlusion. Electrocardiogram (ECG) on admission showed ST elevation in leads I, aVL and V2-6. Since emergency coronary angiography disclosed complete occlusion of the second diagonal branch, intra-coronary thrombolysis (ICT) was performed, superselectively. Transient coronary reperfusion was obtained, however, reocclusion occurred after several minutes. Rescue percutaneous transluminal coronary angioplasty (PTCA) was then performed immediately and blood flow was improved to TIMI grade 2. During these processes, the ST-segment on the ECG changed in leads I, aVL and V2-6 always corresponding to the blood flow of the second diagonal branch. We have not seen a report hitherto in which occlusion of only the second diagonal branch could be a cause of extensive anterior infarction-like ECG changes. Although the mechanism of ECG changes in this patient cannot be clearly explained by conventional concepts, we report this case because it is considered to be very rare. PMID- 8201785 TI - Thrombotic obstruction of the right coronary artery in a postoperative patient with Bland-White-Garland syndrome. AB - A 53-year-old female presented with symptoms of severe chest and back pain associated with oliguria. The patient had a history of exertional dyspnea since the age of 20, and easy fatigability since the age of 27. At the age of 41, she noted marked exacerbation of these symptoms after suffering from a cold and was ultimately diagnosed as having Bland-White-Garland (BWG) syndrome with mitral valve regurgitation. The patient then underwent re-implantation of an anomalous left coronary artery from the pulmonary artery to the posterolateral wall of the aorta. Eleven years later, she re-presented with symptoms of angina and congestive heart failure. Coronary angiography was subsequently performed and a total occlusion of the right coronary artery with probable thrombus was revealed. The right coronary artery was filled via collaterals from the implanted left coronary artery. Mitral regurgitation was noted during angiography. The patient underwent aorto-coronary artery bypass grafting of the right coronary artery and concomitant mitral valve replacement. Her postoperative condition remained excellent. PMID- 8201787 TI - Mental and physical health of middle-aged and elderly women and psychosocial factors. AB - Middle-aged and elderly women with no specific disabilities in their daily life were divided into two groups: those visiting clinics with mild physical symptoms and those not visiting clinics. Those visiting clinics showed significantly lower mental and physical health indices, but satisfaction and emotional support were similar. Although those visiting clinics had significantly more stressful events, no differences were seen in ways they were dealt with. For those not visiting clinics, mental and physical health indices were better in their 60s than in their 50s and got worse again in their 70s, while for those visiting clinics indices were consistently low. Somatic symptoms in the women visiting clinics could be somatic reactions to their life situation from their 50s to their 60s. PMID- 8201786 TI - An autopsy case of hypertrophic cardiomyopathy with pathological findings suggesting chronic myocarditis. AB - Myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM) may play an important role in the function and/or dimensions of the left ventricle. We present an autopsied case of HCM followed for 10 years. A 68-year-woman with HCM underwent trans-aortic myectomy of the interventricular septum in 1979. A significant amount of round cell infiltration, myocardial fibrosis and disarray were observed in the resected specimen. She experienced repeated admissions due to diabetes mellitus and congestive heart failure, and died of renal failure in 1989. An autopsy revealed extensive myocardial fibrosis and significant cell infiltration in the ventricular myocardium. The infiltrating cells were almost all lymphocytes, and the ratio of CD4 to CD8 was 3.8. This ratio was different from that of typical viral myocarditis. This case suggests that there may be an undefined inflammatory process causing fibrosis in HCM, in addition to the ischemia due to intramural small coronary artery stenosis. PMID- 8201788 TI - A tentative classification of "neuroses" based on behavioristic consideration of the pathogenetic mechanisms. AB - Pathogenetic mechanisms of "neuroses" were reconsidered based on a behavioristic framework which includes not only the traditional stimulus-response learning theory but also the concept of conflict proposed by Lewin. Most of the subtypes of "neuroses"--with the exception of panic disorder--were divided into two categories: conditioned fear-related disorders and conflict-related disorders. Phobias have been suggested to be caused by an escape or avoidance behavior motivated by an unconditioned or conditioned fear and obsessive compulsive disorder by an avoidance behavior motivated by a conditioned fear, while such disorders as posttraumatic disorder or hypochondriasis (nosophobia) were considered to be direct manifestations of conditioned fear. Generalized anxiety and depersonalization disorders were suggested to be caused by conflicts, but these conflicts seemed to persist even after the appearance of the symptoms. In contrast, appearances of conversion, somatization, somatoform pain, psychogenic fugue, or psychogenic amnesia were suggested to result in a temporary attenuation of the causative conflicts. PMID- 8201789 TI - Onset of depressive episodes in a woman with seasonal affective disorder of "spring type" coincident with atmospheric temperature, but not with sunshine duration. AB - This is a report on the clinical symptoms and the longitudinal course in a woman with seasonal affective disorder of "spring type." The woman experienced 10 atypical depressive episodes between the ages of 44 and 55. Nine of the 10 depressive episodes were confirmed by the medical chart, and were classified into three categories: two episodes with a psychological stressor, six episodes with the onset in February or March, and an episode starting in August. The onset of the six episodes did coincide with the time the atmospheric temperature rose to 8 degrees Centigrade in spring, but did not relate with the sunshine duration. These findings suggest that the change in atmospheric temperature played an important role in triggering off her depressive episodes. PMID- 8201790 TI - A study of borderline personality disorder from the viewpoint of ego functions. AB - Twenty-eight Borderline Personality Disorder patients (BPD) (by DSM-III-R) were compared with 19 neurotic patients by consulting clinical charts and an interview. The clinical features and ego functions were examined. The results brought this conclusion: (1) Disorders of ego functions of BPD covered a wide range, and were especially noted in object relations. Brief psychotic experiences, depressive experiences, and impulsiveness were the characteristics of the clinical features of BPD. An examination chiefly from the viewpoint of ego functions brought two more conclusions: (2) BPD could be partly included in the schizophrenia spectrum and the affective disorder spectrum, (3) BPD can be divided into two: (a) A Core Group with impulsiveness, (b) A Serious Group with impulsiveness, and brief psychotic experiences and/or depressive experiences. PMID- 8201791 TI - Mental health in family members living with elders. AB - We assessed the mental health conditions of 217 subjects who took care of elders at home, using our depression scale by the surveillance of the elders living at home in Ibaraki Prefecture. An analysis was made on how depression in the caretakers was related with each item of demographical results of the caretakers and the elders living together at home, and with ADL, depression, dementia, personality change and the personality trait of the elders. Our study revealed that depression, personality change and the viscous character of the elders are three factors associated with depression in the female caretakers. Furthermore, we pointed out the necessity of an education campaign to provide the caretakers with information on the elders' personality and personality change for maintenance of the good mental health of the caretakers living with the elders. PMID- 8201792 TI - Sex differences in schizophrenia: a demographic, symptomatic, life history and genetic study. AB - Twenty-one male and 32 female inpatients who met the criteria of schizophrenia according to the Research Diagnostic Criteria were compared for demographic, symptomatic, life history, and genetic variables. Female schizophrenics were marginally less likely to have auditory hallucinations; They were more likely to have early loss experiences (either bereavement or separation from a parent) before the age of 16. No other differences were found between the men and women. PMID- 8201793 TI - Elevated serum LH and androgens in affective disorder related to the menstrual cycle: with reference to polycystic ovary syndrome. AB - The hypothalamo-pituitary-gonadal axis was studied in 12 young women with manic depressive or psychotic symptoms which obviously fluctuated in association with the menstrual cycle, and also in 36 psychiatric patients with other diagnoses. The hormonal features frequently observed among these 12 cases were elevated basal LH (8 of 12 cases), decreased basal FSH (6 of 12), elevated serum testosterone (6 of 12), androstenedione (5 of 12) and/or dehydroepiandrosterone sulfate (3 of 11). These abnormalities resemble those of polycystic ovary syndrome (PCOS). An ultrasonographical study revealed polycystic changes in 8 out of the 12 cases. In 10 cases clomiphene citrate was administered, and was effective in 8. In comparison with the pathophysiology of PCOS, a possible relationship was suggested between the psychiatric problems and the PCOS-like hormonal abnormalities in these cases. PMID- 8201794 TI - Water intoxication in a schizophrenic patient with rhabdomyolysis. AB - We report a case of water intoxication in a 54-year-old female schizophrenic patient with rhabdomyolysis. She had been admitted to a mental hospital, and treated with spiperone 6 mg daily. On August 3, 1992, the coma following a convulsion occurred. Laboratory data initially showed marked hyponatremia and hypochloremia with decreased serum potassium, and a gradual increase in serum creatine phosphokinase (CPK). The elevation in serum CPK with marked hyponatremia observed in the present patient was probably caused by excessive drinking of water. In this patient, the CPK elevation revealed the rhabdomyolysis. PMID- 8201795 TI - Sleep disturbance of end-stage renal disease. AB - Sleep disturbance of patients with end-stage renal disease was examined in a sample of 127 patients receiving hemodialysis (HD) therapy. The results indicate that sleep disturbance occurs quite often. Especially, there was a high incidence of sleep disturbance with prolonged HD therapy and with advancing age, and that somatic complications due to long-term HD indirectly influence sleep disturbance. On the effect of drug therapy, levodopa produced significant clinical effects on RLS compared to ordinary hypnotics. Carbamazepine equally tended to produce favorable clinical effects on RLS. PMID- 8201796 TI - Abnormalities in event-related potentials: N100, N200 and P300 topography in alcoholics. AB - Event-related potentials were recorded in 30 abstinent alcoholics, and 30 gender- and age-matched controls during a two-tone discrimination (odd ball) task. All the subjects were free from medication and dextral. The amplitudes of N100, N200 and P300 in the alcoholics were reduced and the P300 latency prolonged as compared with those of the controls. A P300 amplitude reduction occurred in the left and midline frontal, and the left and midline central regions. This is the first report of the amplitude of P300 being markedly decreased in the left hemispheres of the brains of the alcoholics. The results are discussed in terms of the cognitive dysfunctions of alcoholics. PMID- 8201797 TI - Computerized EEG and brain imaging studies in untreated schizophrenic patients: a report of seven cases. AB - We undertook routine EEG, Z-map, CT and PET scans in seven acute untreated schizophrenics. Routine EEGs showed slower activity in only one case. However, the Z-map showed slower activity in all the cases. CT demonstrated brain atrophy in three of the cases, and PET revealed hypofrontality in two, right hypoparietality in four, and both conditions in one case. There was no relation between CT and PET or the Z-map. However, a significant increase in alpha 1 activity was demonstrated on the Z-map in cases who were found to be the parietal type on PET; this was not conspicuous in the frontal type on PET. Moreover, in three of the patients, the Z-map findings were similar to the lesion indicated on PET. PMID- 8201798 TI - Functional brain imaging of a catatonic type of schizophrenia: PET and SPECT studies. AB - A brain imaging study was conducted in the case of a catatonic type of schizophrenia (DSM-IIIR) by applying (i) positron emission tomography (PET) and (ii) single photon emission computed tomography (SPECT). A PET study using [18F] 2-fluoro-2-deoxy-D-glucose revealed a lower glucose utilization in the dorsal frontal and parietal lobes of both cerebral hemispheres. Correlative SPECT studies using [123I]-iodoamphetamine showed a diminished regional cerebral blood flow in similar regions of the cerebral hemisphere. A three-dimensional volume rendering method of the SPECT images (TITAN) identified the dorsal region of the fronto-parietal lobe as the most severely affected region. These patterns of deficits implicated the role of the dorsal frontal and parietal lobes in the pathogenesis of catatonic syndromes. PMID- 8201799 TI - A case of protein C deficiency associated with cerebral infarction and obstruction of deep leg and inferior mesenteric veins. AB - Protein C, a vitamin K-dependent protein, is a blood coagulation inhibitor. Its deficiency causes systemic thrombosis. A 31-year-old woman developed cerebral infarction followed by late psychomotor seizures, and thrombosis in the inferior mesenteric vein and bilateral crural veins. Her parents were first cousins. Her mother died of cerebral thrombosis in her 30's. Her elder brother died of suspected purpura fulminans immediately after birth. Her protein C activity and protein C antigen level decreased markedly and were less than 5% of those of normal controls and 0.3 microgram/ml, respectively. Her father, a paternal aunt and a maternal uncle also showed a low protein C activity and protein C antigen level. This patient seems to have congenital protein C deficiency which produced thrombosis in the leg veins and the mesenteric vein, probably cerebral infarction. PMID- 8201800 TI - Effects of zopiclone on slow wave sleep and spontaneous K-complexes for normal healthy young adults. AB - Benzodiazepine (BZD) hypnotics have been known to decrease, to some degree, human slow wave sleep (SWS) although they elevate the arousal threshold during sleep. Zopiclone (ZPC), a cyclopyrrolone hypnotic, has attracted the interest of sleep researchers because an increase in human SWS has been reported. Since the increase has not been fully confirmed by all of the studies, the authors investigated the effects of ZPC 10 mg on SWS and the K-complexes for 7 healthy young adults because there is evidence indicating that delta waves consisting of SWS and the spontaneous K-complexes are identical. SWS and st. 4 sleep did not decrease on any of the ZPC nights but st. 3 sleep showed a tendency to reduce on the 1st ZPC night. The frequency of the K-complexes decreased significantly on the 2nd ZPC night and tended to reduce on the 1st ZPC night. Moreover, a significant positive correlation was noted between the decrease rates of SWS and the K-complexes on both the ZPC nights. The authors, therefore, could not obtain any findings suggesting an increase in SWS with ZPC. PMID- 8201801 TI - An autopsy case of Binswanger's disease without hypertension and associated with cerebral infarction in the terminal stage. AB - We report here an autopsy case of Binswanger's disease (BD) without hypertension and associated with cerebral infarction in the terminal stage. The female patient, who was 74 years old at the time of death, had initially demonstrated manic-depressive disorder-like mental disorder, followed by dementia and neurological deficits. A brain CT scan showed white matter low attenuation bilaterally and symmetrically. BD was clinically diagnosed despite the lack of hypertension. In the terminal stage, she suffered an infarction in the left anterior cerebral artery region, and died of pneumonia. Neuropathologically, we found the infarction of the left anterior cerebral artery region, demyelination, fibrillary gliosis, lacunae and arteriosclerosis of the small arteries and arterioles in the white matter. PMID- 8201802 TI - Examination of beta-protein deposits in Alzheimer's cerebral cortices by three dimensional observation. AB - We examined the location of beta-protein deposits (small diffuse plaques) in the cerebral cortices of Alzheimer's patients and aged nondemented controls by observing the methenamine silver stained serial sections. Some vessels, astrocytes or neuronal elements existed near or within the diffuse plaques, and the preamyloids in the plaques were frequently detected in direct contact with vessels, astrocytes or neuronal elements. Although these findings do not demonstrate that the beta-protein within the senile plaques is produced in various cellular elements of the brain, they suggest some associations between beta-protein deposition and vessels, astrocytes or neuronal elements. PMID- 8201803 TI - Intracranial self-stimulation and locomotor traces as indicators for evaluating the homopantothenic acid. AB - Our paper compares the effect of homopantothenic acid (HOPA) and haloperidol (HAL), i.e., representative neuroleptics, on intracranial self-stimulation (ICSS) and locomotor activity. These experiments showed that HOPA inhibited abnormal hyperactivity induced by methamphetamine (MAP) but did not inhibit ICSS which is considered with respect to physiological motivations. On the other hand, haloperidol (HAL) markedly inhibited both ICSS and abnormal hyperactivity induced by MAP. We propose that combined ICSS and locomotor traces can be chosen as indicators for evaluation and developing the new neuroleptics. PMID- 8201804 TI - Changes in local cerebral glucose utilization and dopamine metabolism in the rat brain following acute administration of haloperidol. AB - The effects of acute administration of haloperidol on local cerebral glucose utilization (LCGU) in 26 discrete regions of the rat brain were examined by the quantitative autoradiographic [14C] 2-deoxy-D-glucose technique and compared with the changes in dopamine (DA) metabolism in 13 brain regions examined by a high performance liquid chromatographic assay. A moderate dose (0.25 mg/kg) of acute haloperidol significantly reduced LCGU in a few brain regions; a high dose (1.0 mg/kg) reduced LCGU in 11 regions including the prefrontal cortex, thalamus and other subcortical structures, but not in the caudate putamen or accumbens nucleus. However, the levels of DA metabolite in the caudate-putamen, accumbens nucleus, prefrontal cortex, and medial thalamus were strikingly elevated with both doses of haloperidol. Thus, the changes in LCGU did not parallel presynaptic DA metabolism in terms of direction or distribution, and they might represent mainly the activities of postsynaptic sites. PMID- 8201805 TI - Ipsilateral and bilateral EEG activity from the hippocampus. AB - Using scalp and depth electroencephalography (EEG), we examined the relationship between the surface EEG activity and abnormal EEG discharges in the ipsilateral hippocampus in order to study the neuronal connection between the two cerebral regions. Ictal EEG was divided into 4 groups: 1) unitempo-ipsilateral-bifrontal slow waves, 2) unitempo-ipsilateral-bilateral slow waves, 3) bilateral slow waves, and 4) bilateral slow waves with repetitive spikes. Abnormal depth EEG activity in the hippocampus was classified into paroxysmal discharges and recruiting rhythms. Ictally and interictally, repetitive sharp waves or spikes in the unilateral hippocampus were associated with sharp waves or spikes in the ipsilateral temporal region. These findings suggest that the ipsilateral projection of seizure activity originating in the unilateral hippocampus is dependent upon the function of the subiculum. PMID- 8201807 TI - [Cognition-correlation indices of gender schema: tests of validity]. AB - Four-hundred and seventy-seven subjects evaluated a set of traits and behaviors in terms of how masculine and feminine they were and in terms of how well they represented their real and ideal self-images. Within-individual correlation coefficients between these evaluations were proposed as measures of psychological gender schemata, because they would represent the degree of matching between the subjects' gender-image and ideal/real self-images of gender-related attributes. The present study aims at examining the construct validity of these measures, by testing them to psychological variables that are known to reflect gender identity. The individual difference variables used as criteria were (a) satisfaction with one's own sex, (b) general happiness, (c) self-esteem (d) gender-conflict, and (e) school and occupational achievement need. Correlations between the gender-schema indices and the criteria variables supported the construct validity of those measures. Advantages of the present measurement over the conventional simple trait approach, such as BSRI, or PAQ are discussed. PMID- 8201806 TI - [Rearing related stress and depressive severity]. AB - Mothers' difficulties concerning child-rearing were conceptualized as a rearing related stress (RRS). Eight hundred and seventeen mothers who had six month-olds infants were asked to rate 28 RRS items and 20 items on the depressive severity scale (Zung, 1956). The main results were summarized as follows: (1) Twenty-two items of RRS were analyzed by Hayashi's quantification (type-III) method, and two hypothesized dimensions were extracted. These are named children-related rearing stress (CRRS) and mothers-related rearing stress (MRRS). (2) RRS was related to mothers depressive severity. (3) Linear relationships of "CRRS-MRRS-depression severity" was examined by partial correlation analysis. (4) Primiparae experienced more RRS than multiparae. These results suggested that RRS could be considered as a process, i.e., CRRS influences MRRS and then MRRS influences depressive severity. The RRS model is an accord with the psychological stress model of Lazarus and Folkman (1986). Lastly, possible preventive strategies for mothers' RRS were discussed in the light of RRS model. PMID- 8201808 TI - [Mutual inhibition between positive and negative emotions]. AB - The purpose of this study is to examine the relationship between positive and negative emotions. In study 1, 62 emotional items were selected in order to measure subjective emotional experiences. In study 2, comics, photos and poems were randomly presented to 1,220 college students to induce emotion. Subjects were asked to rate their momentary emotional intensity on two set of 5-point scales (general emotional intensity scale and 62 specific emotional intensity scale). In analysis 1, positive correlations were suggested between general emotional intensity scale and some of the specific emotional intensity scales which were activated by stimuli. In analysis 2, 10 positive and 10 negative emotional items were extracted from 62 items by factor analysis. In analysis 3, 4 and 5, it became clear that the distribution of frequency of correlations of 10 positive x 10 negative items changed according to the general emotional intensity scale. That is, from low to moderate levels of GEIS, the two kinds of emotion had no or slightly positive correlation, but at high level they became to be negatively correlated. From the facts described above, it is concluded that positive and negative emotions is not always independent, but show mutual inhibition in case of high intensity level of one of each emotions. PMID- 8201809 TI - [A hemodynamic comparison of cardiovascular stress responses during mental arithmetic and reaction time tasks]. AB - The primary purpose of this study was to examine the covariation between preload (PL) and other cardiovascular stress responses during mental arithmetic (MA) and reaction time (RT) tasks. PL, stroke volume (SV), cardiac output (CO) and pre ejection period (PEP) were obtained using impedance cardiography. Mean blood pressure (MBP) was measured by the vascular unloading method. Thirty-one male college students were given both MA and RT tasks with a counterbalanced order. Results indicated significant differences in heart rate reactivity which seems to provide evidence for a stronger vagal withdrawal in MA. Changes in CO and MBP were identical in these two tasks which might have resulted from a compensatory change in PL and SV. Specificity of PEP for the increased beta-adrenergic activity was supported by the correlation pattern among PL, MBP and PEP. The results were discussed in the context of cardiovascular regulating mechanisms. PMID- 8201810 TI - [Development of a scale of attitudes toward the roles of liberated men (SARLM)]. AB - A ten-item Scale of Attitudes toward the Roles of Liberated Men (SARLM) based on the factor analysis was developed in order to provide a measure of attitudes toward the roles of liberated and traditional men. The scale was administered to 109 men and 93 women and was examined for its reliability and validity. The goodness-of-fit test indicated that the distribution of the scale scores was very close to the normal distribution. The reliability coefficient was .75, the test retest coefficient with a four-week interval was .94, and the coefficients of the item-total correlations ranged from .43 to .62. These results support the reliability of SARLM. Evidence of the construct validity was derived from the confirmation of five hypotheses regarding sex, educational attainment, age, women's employment status, and husbands' participation in household tasks. SARLM appears to provide a reliable and valid measure for assessing attitudes toward the roles of liberated and traditional men. PMID- 8201811 TI - [Recall and clustering in a patient with memory disorders: with special reference to incidental learning]. AB - A case study of recall and categorical clustering in the patient with organic anterograde amnesia is reported. The stimulus list involved 28 words comprising of eight categories with four items in each, which were individually typed in one letter Kanji character on index cards. This experiment was carried out in incidental learning situation, in which the patient and normal controls were instructed to read aloud each stimulus item. In the test phase, subject was required an immediate free recall orally. Two indices were computed from the test results; the number of words correctly recalled and the level of clustering. While the patient achieved the same number of correct recalls as the controls, she failed to produce the equal level of clustering as the latter. The results suggest that categories or semantic associations were not used by the patient as retrieval cues. The dissociation between recall and clustering in the patient are discussed. PMID- 8201812 TI - [The role of other persons in prospective memory: dependence on other persons inhibits remembering and execution of a task]. AB - This study investigated how other persons functioned in prospective memory process (PMP) and whether planning in memorization for the task could facilitate an appropriate use of other persons. One-hundred and five undergraduates were divided into 2 (facilitating planning in memorization or not) x 2 (facilitating use of other persons or not) groups. The task was to fill out and mail a questionnaire on a specified day. The main results were as follows; 1) subjects who were facilitated using other persons increased dependence on other persons to remember the task. Dependence inhibited execution of the task, because subjects did not use memory aids so much and could not cope with competitive activities, 2) subjects who were facilitated to plan in memorization increased both execution of task (only in the condition which did not facilitate use of other persons) and use of memory aids. These results suggest that implicit use of other persons could induce negative effects in PMP. PMID- 8201813 TI - The experience, expression, and perceived appropriateness of emotions across levels of relationship development. AB - Emotion experience and expression in romantic relationships were investigated. We predicted (a) a curvilinear relationship between level of relationship development and intensity of emotion experience, (b) a curvilinear relationship between level of relationship development and intensity of emotion expression, and (c) a linear relationship between level of relationship development and perceived appropriateness of emotion expression. Two hundred one student and community respondents completed an emotion survey assessing a positive and negative emotion incident they had experienced, the intensity of experience, expression, and degree of appropriateness. Level of relationship development was operationalized by length of relationship. Confirmation for the first two hypotheses was found for negative emotions only. Perceived appropriateness of emotion expression did not vary across levels of relationship development for either negative or positive emotions. PMID- 8201814 TI - Impact of height on assessments of Finnish female job applicants' managerial abilities. AB - The impact of height on assessments of female job applicants' managerial abilities was examined in a study in which 44 subjects assessed 78 subordinates in natural settings. On global evaluations, tall women were regarded, as expected, as better managers than shorter women. On trait-type assessments, only one difference was found between the ratings of tall and short applicants. PMID- 8201816 TI - Romantic love and the spouse selection criteria of male and female Korean college students. AB - Authors of previous studies have shown that men tend to be more romantic than women and that men and women differ in the qualities they value in potential marriage partners. That research has tended to focus on Americans. In this study the hypotheses that men are more romantic than women and that men and women differ in the qualities they value in potential marriage partners were tested with Korean college students as subjects. The results suggest that men are more romantic than women and that women and men differ in their mate selection criteria. A subset of that sample was used to determine the extent to which parental involvement in marriage decisions is considered legitimate. A secondary purpose of the study was to explore the impact of certain linguistic and cultural variables, particularly those involving major life decisions (such as marriage), on the interpretation of such results. PMID- 8201815 TI - Therapeutic use of humor to improve social support in an institutionalized schizophrenic inpatient community. AB - We attempted to use passive communal laughter to improve social support within a chronic schizophrenic inpatient population. Two identical wards were compared on classical measures of social support (emotional and functional), social network (size and dispersion), satisfaction, and the nature of the social relationships (source). The experimental group was exposed to video projection of humorous movies four times daily for 3 months, and the control group to video projections of other, assorted movies at the same rate. In the experimental ward a significant improvement was manifest in the category of "distinct individuals supporting each patient." The difference may have been due to an improvement in the relationship with the staff. No improvement was found on any of the other measures. We concluded that the positive atmosphere that humor creates affects the therapeutic alliance between staff and patients but does not affect other social networks because of the regressed nature of the schizophrenics' social relationships. PMID- 8201817 TI - Gender and work values: a comparative analysis. AB - The results of recent investigations on work values suggest that the contradictory findings in regard to gender differences may be rooted in variations in the underlying structure of the work-values domain. In the present study a definitional framework for work values was proposed and tested. Smallest space analysis (SSA; Guttman, 1968) was performed on the ratings of 24 work-value items by samples of men and women from Hungary, Israel, and the Netherlands. A double-ordered conceptual system, a radex structure, was obtained in each of the samples, reflecting two hypothesized facets: modality of outcome (cognitive, affective, and instrumental) and type of system performance contingency. Essentially the same structure was obtained for women and men. However, women ranked affective outcomes as well as some of the instrumental and cognitive values higher than men did, whereas men ranked some other cognitive (influence, independence, responsibility) and instrumental (pay) items higher than women did. Personal growth and use of abilities were ranked higher by men in some samples and by women in others. PMID- 8201818 TI - Psychological reactance: effects of age and gender. AB - A self-report, attitudinal questionnaire was administered to 1,717 adult Australians between 18 and 40 years old to examine the effects of age and gender on psychological reactance. Analysis yielded a significant age effect: As age increased, the level of reactance tended to decrease. No significant differences in reactance emerged in relation to gender. A significant interaction between age and gender was found. PMID- 8201819 TI - Comparison of couple- and family-initiated marriages in Turkey. AB - In this study, differences between individuals involved in couple- and family initiated marriages were investigated with respect to educational background, relationship duration, context and nature of interactions with partner, degree of perceived disclosure, and ratings of different reasons for marriage. Questionnaires were administered to a sample of Turkish men and women who applied for a marriage license for their first marriage. The results revealed differences between individuals involved in the two kinds of marriages, in terms of background variables as well as context of interaction with partner and cognitions concerning the relationship. PMID- 8201820 TI - Personality, prayer, and church attendance among 16- to 18-year-old girls in England. PMID- 8201821 TI - Effects of interviewer status, touch, and gender on cardiovascular reactivity. PMID- 8201822 TI - Depression and interpersonal rejection: the role of anticipated interaction. PMID- 8201823 TI - Effects of supervisor's gender on American women's trust. PMID- 8201824 TI - Malrotation of the intestine in adulthood. PMID- 8201825 TI - Penetrating carotid artery injury with associated neurologic deficit. PMID- 8201826 TI - Parents encouraging parents. PMID- 8201827 TI - The devil in the lack of details. PMID- 8201828 TI - Cyclic nucleotide phosphodiesterases in the human lung. AB - Although theophylline has been used in the treatment of lung diseases, particularly bronchial asthma, since the nineteenth century, the mechanisms underlying its effectiveness remained poorly understood until quite recently. The identification of cyclic nucleotide phosphodiesterase (PDE)--the enzyme responsible for breaking down cyclic AMP and cyclic GMP within cells--as a target for methylxanthines such as theophylline led to a research effort that has resulted in the characterization of multiple forms of the PDE enzyme and the development of selective inhibitors for some of these forms. Using these drugs, it has been possible to identify the PDE "isoenzymes" in a number of tissues and cells and to demonstrate the functional effects of the inhibition of different PDEs upon these tissues. Studies on the smooth muscle of human airways and pulmonary arteries have identified isoenzyme-selective PDE inhibitors that are effective broncho- and vasorelaxants in vitro, and it is hoped that these agents may be effective in relieving airway obstruction and pulmonary hypertension in patients. In addition, selective inhibitors of certain PDE isoenzymes suppress the proinflammatory functions of a range of immune cells, including the lung mast cell and the alveolar macrophage. Selective inhibitors of PDE isoenzymes are beginning to undergo clinical trials for the treatment of asthma. The advancing understanding of the PDE distribution in the lung and the ever more precise characterization of distinct enzyme proteins should allow the development of site selective drugs for the treatment of lung diseases, while minimizing the systemic side effects associated with nonselective PDE inhibitors such as theophylline. PMID- 8201829 TI - Cyclophosphamide induced early biochemical changes in lung lavage fluid and alterations in lavage cell function. AB - The present investigation evaluated the changes in bronchoalveolar lavage fluid (BALF) biochemical constituents and indices of bronchoalveolar lavage cell functions to detect early lung injury in rats following intraperitoneal administration of cyclophosphamide (CP). Rats were exposed to a single intraperitoneal injection of CP (200 or 300 mg/kg body weight). Experimental and control rats were sacrificed at various time intervals (2, 3, 5, 7, 11, 21, and 42 days after cessation of exposure), and lung lavage was performed to examine several markers of lung injury. Biochemical analyses revealed dose-related increases in BALF angiotensin converting enzyme activity, total protein, lactate, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase (NAG) levels on days 2, 3, 5, 7, and dose-related increases in albumin, alkaline phosphatase, acid phosphatase, and lipid peroxidation on days 2, 3, 5, 7, and 11 after CP treatment. In contrast, reduced levels of ascorbic acid and glutathione (GSH) content were observed in lung lavage fluid. We also examined bronchoalveolar lavage cells for acid hydrolases (acid phosphatase, beta-glucuronidase, NAG) and GSH content. Activity of acid hydrolases was slightly elevated on day 2 and peaked on days 3, 5, and 7. However, lavage cell GSH content was decreased. Thus, measurements of pulmonary changes by analyzing lavage fluid and lavage cell functions seems to be a useful marker for assessing the early onset and development of CP-induced lung injury. PMID- 8201830 TI - VIP antagonists enhance excitatory cholinergic neurotransmission in the human airway. AB - It has been reported that a low concentration of exogenously applied vasoactive intestinal peptide (VIP) suppresses the release of acetylcholine (ACh) from vagus nerve terminals in the ferret and feline trachea. There has been, however, no documentation of the prejunctional action of VIP in the human airway. We observed the effects of VIP and VIP antagonists on cholinergic excitatory neuro-effector transmission in the human bronchus to study the possible role of endogenous VIP on excitatory neurotransmission. In the human bronchus, VIP (10(-10) to 10(-7) M) showed no effect on either the contractions evoked by electrical field stimulation (EPS) or those evoked by ACh. To investigate the possible role of endogenous VIP on the human bronchus, we observed the effects of the VIP antagonists [4-Cl-D-Phe6,Leu17]-VIP and [Ac-Tyr1,D-Phe2]-GRF(1-29)-NH2 on excitatory neuro-effector transmission. Both VIP antagonists (10(-8) M) significantly enhances the contractions evoked by EFS without affecting the ACh sensitivity of smooth muscle cells. These results indicate that VIP antagonists have a prejunctional action that enhances excitatory neurotransmission. This study suggests that endogenous VIP may suppresses ACh release from the vagus nerve terminals in the human airway. It is also suggested that exogenously applied VIP may be inactivated by some mechanism in the human airway. PMID- 8201831 TI - Guinea pig lung inflammatory cell changes following acute ozone exposure. AB - The time course of inflammatory cell infiltration into guinea pig lungs following a single 4 h exposure to 2 ppm O3 was established by measuring the changing cell populations recovered by both bronchoalveolar lavage (BAL) and collagenase tissue digestion. Analysis of BAL-recovered albumin was used as an indicator of permeability damage and demonstrated an increase immediately following ozone exposure, reaching a maximum within 24 h, but returning to air-control levels by 7 days post-ozone exposure. A twofold enhancement in macrophages was observed in the lavage-recovered cell population after 2 days, returning to air-control numbers by 7 days. Collagenase digest-recovered monocytes and macrophages, identified by nonspecific esterase staining, were found to be elevated between 2 and 14 days following O3 exposure. Immediately following O3 exposure, a 4.5-fold increase in collagenase digest-recovered neutrophils was observed, with a subsequent decline to air-exposed lung levels during the next 12 h. In contrast, BAL-recovered neutrophils were observed to be increased immediately following O3 exposure at a level that was sustained for up to 3 days. The tissue accumulation of neutrophils was not associated with their subsequent appearance in the lavageable spaces. Although significant increases in collagenase digest-recovered eosinophils could not be detected, lavage-recovered eosinophil numbers were transiently increased by threefold after 3 days. By employing both BAL and collagenase digestion to evaluate this model of reversible lung injury, this study demonstrated that the use of BAL-recovered cell measurements alone does not adequately reflect the early inflammatory cell changes taking place within oxidant-exposed lungs. PMID- 8201832 TI - Value of serum and effusion fluid CEA levels for distinguishing between diffuse malignant mesothelioma and carcinomatous pleural metastases. PMID- 8201833 TI - Voluntary donor agencies in antileprosy work: present contribution and probable future. PMID- 8201834 TI - T lymphocyte reactivity of leprosy patients and healthy contacts from a leprosy endemic population to delipidified cell components of Mycobacterium leprae. AB - In this study, we measured in vitro proliferative responses of peripheral blood mononuclear cells from both leprosy patients across the clinical spectrum and also healthy contacts from a leprosy-endemic population to delipidified cell components of Mycobacterium leprae (DCC) and Dharmendra lepromin. Dharmendra lepromin was poor in inducing in vitro T cell proliferation in all the study groups, even though it elicited marked in vivo skin test reaction in tuberculoid leprosy patients and healthy contacts. In contrast, Dharmendra preparation of BCG induced marked T-cell response in tuberculoid as well as bacterial index negative lepromatous patients. DCC induced a significantly higher lymphoproliferative response than Dharmendra lepromin in all study groups. A significant positive correlation was observed between the lymphoproliferative responses to DCC and BCG. The present study, based on a large number of leprosy patients and healthy contacts, clearly demonstrates that DCC, depleted of glycolipids and lipopolysaccharides, is a good antigenic preparation for evaluating T-cell reactivity to M. leprae. PMID- 8201835 TI - A randomized clinical trial of two single-dose treatments for paucibacillary leprosy. AB - We compared 2 single-dose regimens for the treatment of paucibacillary leprosy in a randomized clinical trial in Zaire. The regimens were: C2 (rifampicin 40 mg/kg and 1200 mg clofazimine once) and C4 (rifampicin 40 mg/kg, clofazimine 100 mg, DDS 100 mg and ethionamide 500 mg once). An analysis of the results of patients enrolled between May 1987 and December 1988, with a maximum follow-up of 4 years, is presented. A total of 622 patients were enrolled and 14 paucibacillary and 1 multibacillary relapses occurred. The overall paucibacillary relapse rate was 2.4 per 100 person years. This relapse rate was higher for older patients as well as for patients with 3 or more lesions. The probability of cure at 3 years is 0.816 for C2 and 0.823 for C4, the difference not being statistically significant. The probability of cure at 3 years with either regimen is higher for patients with 1 or 2 lesions (0.872) than for patients with 3 or more lesions (0.787), and it is higher for patients with a bacterial index of 0 (0.831) than for patients with a bacterial index of 1 (0.699). These results are compared to other studies. We also discuss the potential of single-dose treatment regimens for paucibacillary leprosy. PMID- 8201836 TI - The effect of footwear on sensory testing in leprosy. AB - The aim of this study was to identify the effect of footwear on sensory testing in leprosy. This was achieved by using 3 methods of sensory testing within 1 district of East Africa. We included 72 leprosy patients and 36 patients (nonleprosy patients) in the study and these were subdivided into 2 groups, depending on whether they normally wore shoes or went barefoot. The methods used were the WHO sensory test, graded monofilaments and the biothesiometer. The results showed significant differences in the threshold levels between both groups of patients with the biothesiometer and monofilaments, demonstrating the importance of having separate values when screening for leprosy and assessing which patients are at the most risk of developing ulcers. The importance of having quantitative methods of testing was also demonstrated, as only then can the results be sufficiently standardized to identify the at-risk groups and also be sufficiently sensitive to differentiate between shoe wearing and nonshoe wearing patients. PMID- 8201837 TI - Understanding the attitude of multidisciplinary teams working in leprosy. AB - This study investigated the attitude of health personnel who were working for the National Leprosy Eradication Programme (NLEP) in India to their leprosy patients. These personnel were studied individually and as homogeneous groups so that comparisons were possible within and among the groups, and between the groups in different regions who were conducting similar health programmes, with a difference in length of between 1 and 5 years. The sample population was the NLEP employees of 2 state governments, consisting of 8 health professional groups. A questionnaire was developed for each of these groups to elicit information on 5 aspects of the relationships with their patients. The main outcome of the study was that two-thirds of the personnel tested possessed the 'minimum desirable' interaction with their patients. The quality of their relationships differed only among work specialities, but was consistent within the same speciality in different regions; this pattern was unchanged after 5 years of a multidrug (MDT) programme. A further analysis showed that although they possessed a caring attitude towards patients from low socioeconomic classes, a domineering attitude towards these same patients was also prevalent. Analysis according to speciality revealed that laboratory technicians had the highest "desirable attitude" (74.67%) and health educators had the lowest (57.5%), while the rest of the team members fell in between. The stigma shown towards leprosy was higher among doctors when compared to the rest of the team members. Discussion is based on the performance, overall and in each of its 5 facets, of each the professional groups with reference to their job descriptions and with similar studies undertaken earlier. PMID- 8201838 TI - Type 1 reaction, neuritis and disability in leprosy. What is the current epidemiological situation? AB - Type 1 reaction is one of the major causes of nerve damage in leprosy patients leading to disabilities of varying severity. Though this complication of leprosy has been extensively described, we still know very little of its natural history and of the factors which may predispose to it. This paper examines the descriptive and analytic epidemiology of these reactions in leprosy. We find that they vary greatly in clinical expression, time of onset, duration and severity, which has important implications for the way they are handled in the context of leprosy-control programmes. We review the various risk factors that have been suggested over the last 30 years and the evidence of their utility in identifying 'high-risk' patients is assessed. We then review the specific aspects of neuritis and disability in leprosy and examine the contribution of Type 1 reaction to leprosy-associated disabilities. The prospects for early detection and prevention of Type 1 reaction are examined in the light of current knowledge, both at research and at the leprosy control level. PMID- 8201839 TI - Identification of a human delta opioid receptor: cloning and expression. AB - The delta opioid receptor is an important target for analgesic drug development. This report describes the identification of delta opioid receptor clones from human cDNA libraries and the preparation of a human delta receptor cDNA in the pcDNA3 expression vector for transfection studies. The cDNA encodes a 372 amino acid protein that has 93% amino acid identity to mouse and rat delta receptors. COS-7 cells transfected with this clone express over 1.0 pmol receptor/mg protein when measured by saturation binding with [3H]naltrindole. The delta receptor selective ligands NTB, BNTX, [4'-Cl-Phe4]DPDPE and [D-Ala2,Glu4]deltorphin all have Ki values under 10 nM while the affinities of the mu and kappa opioid receptor ligands CTAP and U-69593, respectively, are over 4.0 microM. Agonists show binding to multiple affinity states of the receptor consistent with the presence of G-protein coupled and uncoupled forms of the expressed receptor. The 8-fold higher affinity of NTB relative to BNTX suggests that the human delta receptor is of the delta 2 subtype. PMID- 8201840 TI - Time course study for antigen-induced airway hyperreactivity and the effect of soluble IL-5 receptor. AB - To study the role of IL-5 in allergic airway hyperreactivity, the time course for the production of cytokines, the infiltration of inflammatory cells and the onset of airway hyperreactivity after three inhalations of antigens were studied in mice. The effect of the soluble alpha-chain of murine recombinant interleukin-5 receptor (sIL-5R alpha) on these phenomena was also examined. Whereas IL-5 and IL 4 were produced in significant amounts, IL-1, IL-2 and gamma-interferon (gamma IFN) were not detected even after three antigen inhalations. Monocytes and eosinophils but not neutrophils increased significantly after the third antigen exposure. The airway responsiveness to acetylcholine increased after the third aeroantigen-challenge. sIL-5R alpha, administered after each antigen-challenge, suppressed BAL eosinophilia with little effect on airway hyperreactivity. PMID- 8201841 TI - Unconjugated bilirubin inhibits the oxidation of human low density lipoprotein better than Trolox. AB - Oxidative modification of human low density lipoprotein (LDL) has been implicated in plaque formation in blood vessels leading to atherogenesis. Conversely, there is increasing evidence that prevention of LDL oxidation reduces the incidence of coronary artery disease. Here, we have compared the effect of unconjugated bilirubin (Bu) and Trolox (a vitamin E analogue) on the oxidation of LDL after treatment with Cu2+ under defined conditions. We observed that Bu, at or near the normal serum level (i.e. 17 microM) effectively inhibits oxidation of LDL, while it takes at least 500 microM Trolox to achieve a similar effect. This means that, on a per mole basis, Bu is > 20 times more effective than Trolox in preventing LDL oxidation. The oxidation of LDL was assessed by agarose gel electrophoresis. This was further corroborated by assaying the malondialdehyde formed upon reacting the presumptive peroxidation product(s) of LDL with thiobarbituric acid. Thus, we have directly verified that Bu and, less so, Trolox, can each prevent the oxidative damage of LDL in vitro. Our result supports the contention that Bu as an endogenous antioxidant can prevent LDL oxidation and hence reduce the risk of atherogenesis. PMID- 8201843 TI - Effect of pinaverium and other calcium channel blockers on contraction of isolated gastric antral smooth muscle cells caused by gastrointestinal hormones. AB - Gastrointestinal hormones, gastrin, cholecystokinin (CCK), and motilin, are known to induce contraction of digestive smooth muscle cells from various species. In this paper, we studied the effect of calcium channel blockers, diltiazem, nicardipine, and pinaverium on the hormone-dependent contraction of smooth muscle cells isolated from rabbit antrum. Gastrin, CCK-8, and motilin caused dose dependent contraction with EC-50 values in the physiological range (10-100 pM). This contractile effect was dependent upon extracellular calcium for gastrin and CCK-8 but not for motilin. When used alone, calcium channel blockers diltiazem, nicardipine, but not pinaverium, caused a weak but significant contraction of the cells. Pinaverium inhibited both gastrin- and CCK-8-induced contractions with IC 50 values of 1 nM and it was much less potent in the inhibition of motilin induced contractions (IC-50 = 25 nM). The effect of pinaverium was equivalent to that of diltiazem in the inhibition of CCK-8- or gastrin-induced contractions. Both drugs were slightly more potent than nicardipine (IC-50 = 10 nM versus 1 nM for pineaverium and 5 nM for diltiazem). In contrast, diltiazem and pinaverium were less potent against motilin stimulation, diltiazem being 5 times more potent than pinaverium. In conclusion, it appears that since Ca2+ antagonists pinaverium, diltiazem and nicardipine inhibited contraction of smooth muscle cells stimulated by gastrointestinal hormones, "L-type" calcium channels of the plasma membrane might also be regulated through occupation of gastrin or CCK receptors. PMID- 8201842 TI - Changes in bile acids metabolism during rat hepatocarcinogenesis: causative or unrelated? AB - In the present paper, we have aimed at studying the variations in the metabolism of bile acids occurring during an hepatocarcinogenic process induced in male Wistar Rats by the biphasic protocol of Solt and Farber. Bile acids concentrations was measured in the liver. The most significant changes have been observed 5 weeks after the beginning of the treatment, it means one week after the selection treatment consisting in 2-acetylaminofluorene administration: the increase in cholic acid, and of its intestinal metabolite, deoxycholic acid, and of alpha- and beta- muricholic acids, are likely to be a consequence of an acute effect of 2-acetylaminofluorene. To test for the putative implication of liver bile acids modifications in the selection effect of 2-acetylaminofluorene, diethyl-nitrosamine-pretreated rats were fed a diet containing 1% lithocholic acid, a treatment that induces essentially the same qualitative changes in liver bile acids, as 2-acetylaminofluorene does: no selection effect of lithocholic acid could be demonstrated. These results suggest that changes in bile acid metabolism occurring early in hepatocarcinogenesis are more likely to be secondary than causative events. The same conclusion comes from the results obtained later on in the process, where there is only a high increase in liver cholic acid and deoxycholic acid concentrations. PMID- 8201844 TI - 4-Dimethylaminophenethylamine, a sensitive, specific, electrochemically detectable monoamine oxidase-B substrate. AB - 4-Dimethylaminophenethylamine (DMAPEA) was characterized as an MAO substrate. This compound was unaffected by MAO-A, while its oxidation by MAO-B was linear as a function of both time and enzyme concentration, with Km = 5.8 microM and Vmax = 21.2 pmol/min/mg protein, using a crude rat brain mitochondrial suspension as source of MAO. Both DMAPEA and its oxidation product, 4-dimethylaminophenylacetic acid (DMAPAA), can be detected electrochemically at 0.85 V. The high MAO-B affinity and selectivity of DMAPEA, together with its low oxidation potential, make this molecule a unique tool to determine MAO-B activity in a wide variety of tissue preparations using HPLC-ED. PMID- 8201845 TI - Modulation of peripheral benzodiazepine receptors in female rat genital organs by various gonadal steroids. AB - Peripheral benzodiazepine receptors (PBR) in the ovary, oviduct, uterus, and kidney of immature rats were studied under short- and long-term treatment with testosterone (T), progesterone (P4), and diethylstilbestrol (DES). A significant increase in PBR specific binding was observed after 4 days' treatment with T in the ovary (1.6-fold), oviduct (2.0-fold), and uterus (1.4-fold) compared with intact rats. Four days' treatment with P4 increased PBR specific binding in the ovary (1.5-fold), but no changes were detected in the oviduct or uterus. In contrast, PBR specific binding was significantly reduced by 10 days' treatment with T or P4: 40 and 12%, respectively, in the ovary and 35 and 40%, respectively, in the oviduct. Ten days' treatment with T reduced PBR specific binding in the uterus by 25%, but the same interval of treatment with P4 did not alter specific binding in the uterus. Four or 10 days' treatment with DES significantly increased PBR specific binding in the ovary (1.5-fold), oviduct (2.4-fold), and uterus (1.9-fold). Scatchard analysis revealed that the changes in the PBR specific binding were due to a change in PBR density values rather than PBR affinity values. No change in PBR specific binding was found in the kidney following any of these treatments. Taken together, it is suggested that PBR density in the ovary is altered by exogenously administered steroids that usually are biosynthesized in the ovary. Additionally, the altered PBR density in the oviduct and uterus via the various steroids employed may imply that changes occurring in ovarian steroidogenesis should affect PBR density in these organs. PMID- 8201846 TI - The intestinal uptake of "enzymatically-stable" peptide drugs in rats as influenced by D-glucose in situ. AB - In previous in situ and in vivo rat perfusion studies, the intestinal absorption of several low molecular weight drugs was increased by the presence of luminal D glucose. The intent of this study was to determine the potential of this fed state effect to improve the intestinal uptake of poorly permeable, small peptide and peptide-like drugs. Jejunal wall permeabilities (Pw*) of di-(D-kyotorphin), tri-(cephradine), hexa-(growth hormone releasing peptide, GHRP-6) and octa (octreotide, a somatostatin analogue) peptides and corresponding net water fluxes were determined in rats using an in situ single-pass perfusion technique. Glucose was shown to enhance the uptake of the smaller (di- and tri-) peptides but not the larger peptides despite the fact that glucose elicited a significant net water absorption with each of the four peptide drugs. It is concluded that glucose enhances jejunal permeabilities of smaller peptides by solvent drag and the enhancement is limited in situ by peptide molecular size. The studies with nonmetabolizable 3-O-methylglucose suggest that the augmentation of the proton gradient across the transmucosal membrane by glucose contributes to the carrier mediated transport observed with the smaller peptides. PMID- 8201847 TI - TCV-116, a newly developed angiotensin II receptor antagonist, induces regression of cardiac hypertrophy through suppression of the tissue renin-angiotensin system in spontaneously hypertensive rats. AB - Previously, we reported that an orally active angiotensin II (Ang II) receptor antagonist Losartan induces regression of left ventricular hypertrophy with reduction in the tissue Ang II contents in spontaneously hypertensive rats (SHR). To further address the role of the cardiac renin-angiotensin system in the pathophysiology of hypertensive left ventricular hypertrophy, we examined the effects of TCV-116, a newly developed, highly specific nonpeptide Ang II receptor antagonist, on cardiac hypertrophy and the tissue angiotensin I (Ang I) and Ang II, as well as plasma renin activity (PRA) and Ang II, were determined. Treatment with TCV-116 (1 mg/kg per day) lowered blood pressure markedly. TCV-116 reduced significantly the left ventricular weight by about 11% compared with control animals. The left ventricular Ang I and Ang II contents were lowered by TCV-116 (12.9 +/- 1.4 vs. 30.4 +/- 2.5 pg/tissue, control, p < 0.01, for Ang I; 15.1 +/- 0.6 vs. 18.7 +/- 0.4 pg/tissue, control, p < 0.01, for Ang II), whereas PRA and plasma Ang II concentration were increased by the treatment. With the control and TCV-116-treated animals, there was a significant positive correlation between the left ventricular weight and the tissue Ang II content (r = 0.681, p < 0.01). These results not only further support the view that cardiac Ang II, rather than circulating Ang II, plays an important role in the pathophysiology of left ventricular hypertrophy of this animal model of human hypertension, but imply also that TCV-116 induces regression of hypertensive left ventricular hypertrophy through suppression of the tissue renin-angiotensin system. PMID- 8201848 TI - Differential effects of short-term or prolonged cocaine exposure on peripheral blood cells in mice. AB - The effects of cocaine on the number of murine peripheral blood cells and on phenotypic expression of lymphocyte subsets were examined using different regimens of drug exposure. Cocaine administered to mice for 7 consecutive days at 1 and 10 mg/kg/day reduced the absolute number of circulating white blood cells and the relative number of cells stained as lymphocytes, polymorphonuclear cells and monocytes. Cocaine did not modify the relative proportion between lymphocytes, polymorphonuclear cells and monocytes. Parallely, there were no changes in the percentage of circulating CD4+ and CD8+ lymphocytes, while the number of natural killer cells increased. In sharp contrast, we didn't observe any significant change in peripheral blood cells after 30 days of consecutive drug administrations. PMID- 8201849 TI - Carpal tunnel syndrome surgery may harm patients' hands. PMID- 8201850 TI - Tobacco kills. PMID- 8201851 TI - Church home and hospital: where caring is part of the cure. AB - For 137 years, Church Home and Hospital has been providing high quality health care to the poor, the elderly, and the sick living in the eastern Baltimore metropolitan area. The institution is unusual in many ways, not the least of which is the loyalty of its staff. Prime examples of this loyalty are T.G. Whedbee, Jr., the hospital's president and chief executive officer, who is retiring this year after nearly three decades with Church Home and Hospital, and Jose M. Yosuico, M.D., former chief of staff and past Med Chi president, who has been associated with the institution he loves for 40 years. This dynamic and innovative institution, which made a commitment to serve its urban neighbors when other medical facilities fled to the suburbs, was the first in the state to establish a hospice, an intensive care unit, a residence for patients with Alzheimer's disease, a satellite urgent-care center, and a patient care program based on severity of illness. These are only a few of the many creative programs that the hospital has implemented over the years to enhance patient care- programs that have served as models for hospitals across the nation. PMID- 8201852 TI - Breast cancer prevention trial. AB - The incidence of breast cancer continues to rise and now affects one in eight women, despite major early-detection efforts. The Breast Cancer Prevention Trial (BCPT), under the auspices of the National Surgical Adjuvant Breast and Bowel Project (NSABBP), will evaluate the effect of tamoxifen in reducing the incidence of invasive breast cancer, breast cancer mortality, cardiovascular mortality, and bone fractures. A total of 16,000 healthy women 35 years of age or older will be randomized to receive tamoxifen or a placebo over a five-year period. As of March 1993, 42% of the needed study participants had been enrolled in the trial. The University of Maryland is participating in the BCPT, and Maryland physicians can refer potential study participants to 12 locations throughout Maryland. PMID- 8201853 TI - Fifteen things you should know about new Maryland laws when making health care decisions. AB - Recent dramatic changes to Maryland law regarding health care decision making for incapacitated patients will have significant impact on the role of physicians in making these decisions. On October 1, 1993, the newly passed Maryland Health Care Decision Act took effect, and revisions to state guardianship laws were implemented. The laws, which Governor Schaefer approved on May 11, 1993, modify existing statutory language pertaining to the four legal tools available for making health care decisions for a person when he or she becomes incapacitated: (1) living wills, (2) substituted consents for medical procedures, (3) health care power of attorney appointments, and (4) guardianship proceedings. This article summarizes 15 important points in these new or revised Maryland laws on health care decision making. PMID- 8201854 TI - A computerized geriatric assessment designed for use in primary care physicians' offices. AB - Comprehensive geriatric assessments have generally been recognized as beneficial for frail elderly patients. However, the complexity of these evaluations has usually required that they be performed in a multidisciplinary setting. Staffing requirements, time commitment, new skill requirements, and reimbursement problems serve as impediments for primary care physicians performing these examinations. Computer technology may be the solution to these problems. A software program has been developed which allows primary care physicians to perform a sophisticated functional assessment on an outpatient basis without the use of a multidisciplinary team. Problems are identified by the computer-assisted protocol and patients are referred for appropriate management. Thus, the physician maintains a primary role in case management. The program is cost effective because it does not require additional staff to operate it and it effectively uses CPT and ICD9 coding. PMID- 8201855 TI - Smoking, age, and sex in carotid artery atherosclerosis: a review of 3,865 carotid duplex scans. AB - The association of smoking with atherosclerotic disease is widely accepted, but inadequate recording of smoking histories lead to a wide range of reported correlations with this important risk factor. Additionally, there has been a controversial concept that smoking causes atherosclerosis in men to a greater degree than in women. In this study, carotid duplex scans (CDS) were performed on 3,865 referred patients who gave reliable smoking histories. Participants who had smoked for ten years or more were classified as "smokers" regardless of their present status. The finding of significant plaque (over 50% stenosis) was compared in smokers and nonsmokers at all ages and for both sexes. The findings in almost 4,000 patients referred for carotid duplex scans are presented and show that smoking is a potent risk factor in carotid artery arteriosclerosis. Both men and women are equally affected. PMID- 8201856 TI - Access to legal resources. PMID- 8201857 TI - Advanced techniques for the treatment of severe isoimmunization. PMID- 8201858 TI - Supporting family functioning during a high-risk pregnancy. PMID- 8201859 TI - Critical pathways in the intensive care & intermediate care nurseries. PMID- 8201860 TI - Phenytoin. It's not just for seizures anymore. PMID- 8201861 TI - Administration of infant formula through the intravenous route: consequences and prevention. PMID- 8201862 TI - Power analysis: Part II. PMID- 8201863 TI - Infant care: teaching the basics. PMID- 8201864 TI - Advanced practice nursing. PMID- 8201865 TI - A struggle with optimal child care. PMID- 8201866 TI - In support of storytelling. PMID- 8201867 TI - HIB: a new conjugate and a combination vaccine. PMID- 8201868 TI - Nursing research: everybody's business. PMID- 8201869 TI - Teddy bear clinics: a huge community project. PMID- 8201870 TI - Locating case law. PMID- 8201871 TI - Systematic data collection: I. PMID- 8201872 TI - Infant care: teaching the basics, part II. PMID- 8201873 TI - Prostaglandins: a variety of uses for clinical practice. PMID- 8201874 TI - Immunization--a preventive measure. PMID- 8201875 TI - Advanced practice nurses in an environment of health care reform. PMID- 8201876 TI - What pediatric hospital nurses know about immunization. PMID- 8201877 TI - Standards for pediatric immunization practice. National Vaccine Advisory Committee. PMID- 8201878 TI - Breaking down the barriers. PMID- 8201879 TI - Current immunization guidelines. CDC. PMID- 8201880 TI - Pain and pain relief in the neonate. PMID- 8201881 TI - Short, shorter, shortest: improving the hospital stay for mothers and newborns. PMID- 8201882 TI - Avoiding collisions with challenging families. PMID- 8201883 TI - Dr. Welford's chart notes. AB - We examined a robust and highly customizable menu-based charting program created and maintained by a practicing physician. The program offers a number of well conceived and often elegantly executed features, integrating clinically related administrative and decision-support functions at a reasonable price. The drawbacks are lack of a graphic interface with mouse support, limited importing and exporting abilities, and dependence on a single individual for maintenance of the program. PMID- 8201884 TI - A survey of office computing in medical practices. AB - A survey of computer use for administrative functions in private medical practices showed that the use of computers for practice management is increasing: almost 75% of the practices responding used office computers. Satisfaction with the systems was limited, however, and the more frequent users (administrative staff members) were less satisfied than the less frequent users (physicians). Satisfaction with a computing system was directly related to its usefulness and its compatibility with existing work practices. Office systems continue to be used most for financial tasks, such as billing and insurance filing. A desired and necessary change would be an improved ability for clinical record keeping. Physicians' notes were transcribed in more than half the practices surveyed; if systems were designed with physician-friendly interfaces for record keeping, the costs associated with transcription could be cut. PMID- 8201885 TI - Life after conversion to mainframe Unix. PMID- 8201886 TI - Compression, elation, and depression. PMID- 8201888 TI - A British view of SCAMC. Symposium on Computer Applications in Medical Care. PMID- 8201887 TI - The computerized patient record: privacy and security. PMID- 8201889 TI - Increasing computer productivity while reducing costs. PMID- 8201890 TI - A computer system for teaching surgery based on hypertext technology. PMID- 8201891 TI - OCIS: 15 years' experience with patient-centered computing. AB - In the mid-1970s, the medical and administrative staff of the Oncology Center at Johns Hopkins Hospital recognized a need for a computer-based clinical decision support system that organized patients' information according to the care continuum, rather than as a series of event-specific data. This is especially important in cancer patients, because of the long periods in which they receive complex medical treatment and the enormous amounts of data generated by extremely ill patients with multiple interrelated diseases. During development of the Oncology Clinical Information System (OCIS), it became apparent that administrative services, research systems, ancillary functions (such as drug and blood product ordering), and financial processes should be integrated with the basic patient-oriented database. With the structured approach used in applications development, new modules were added as the need for additional functions arose. The system has since been moved to a modern network environment with the capacity for client-server processing. PMID- 8201892 TI - International transfer of the Johns Hopkins Oncology Center clinical information system. AB - The transfer of the Johns Hopkins Oncology Center clinical information system to an Australian tertiary care center began in 1982. The converted system was installed for use by the hospital administration in 1991, and it is now used extensively in management and patient care. This article discusses the original software, the applications implemented, and the problems encountered and overcome, as well as the role of the hospital administration in the development and subsequent freezing of the system. PMID- 8201893 TI - HIV/AIDS policies and sports: the National Football League. AB - With the assistance of highly respected experts in the field of HIV/AIDS, the NFL has developed a comprehensive policy that should decrease the spread of HIV and any other blood-borne pathogens among its players and medical staff. Transmission of HIV infection is likely to be rare in the NFL. This is supported by the fact that in over 10 yr of the AIDS epidemic, the CDC has not attributed one AIDS case to athletic competition. Whatever the rate of HIV infection, on-the-field transmission is certainly less frequent than hepatitis B, which is manyfold more transmissible than HIV. Based on these facts, a player with HIV infection poses virtually no threat to others or himself by further athletic participation in the NFL. In addition, the relatively short average playing career of an NFL player and the extended period between HIV contraction and development of AIDS symptoms decrease the prospect that a player's HIV-positive status would affect his athletic performance. Consequently, HIV testing should remain voluntary, and continued participation in the NFL of HIV-infected players should remain a private decision between the player and his physician. PMID- 8201894 TI - An acute myocardial infarction occurring in an anabolic steroid user. AB - Anabolic-androgenic steroid abuse is prevalent and has been associated with numerous adverse effects. The case being presented is of an amateur weight trainer, who suffered an acute myocardial infarction; his only significant risk factor was his nonmedical use of an anabolic steroid, nandrolone decanoate. This case presentation discusses the hematologic effects of this class of drugs and the subsequent impact on ischemic heart disease. PMID- 8201895 TI - Risk and trigger factors for the development of eating disorders in female elite athletes. AB - This study examined risk factors and triggers for eating disorders in female athletes. Subjects included were all of the elite female athletes in Norway (N = 603), ages 12-35 yr, representing six groups of sports: technical, endurance, aesthetic, weight dependent, ball games, and power sports. The Eating Disorder Inventory was used to classify individuals at risk for eating disorders. Of the 117 athletes defined at risk, 103 were administered a structured clinical interview for eating disorders. A comparison group was also interviewed, consisting of 30 athletes chosen at random from a pool not at risk and matched to the at-risk subjects on age, community of residence, and sport. Ninety-two of the at-risk athletes met criteria for anorexia nervosa, bulimia nervosa, or anorexia athletica. The prevalence of eating disorders was higher in sports emphasizing leanness or a specific weight than in sports where these are less important. Compared with controls, eating disordered athletes began both sports-specific training and dieting earlier, and felt that puberty occurred too early for optimal performance. Trigger factors associated with the onset of eating disorders were prolonged periods of dieting, frequent weight fluctuations, a sudden increase in training volume, and traumatic events such as injury or loss of a coach. PMID- 8201896 TI - Cardiovascular responses to submaximal arm and leg exercise in cardiac transplant patients. AB - We examined whether an increase in stroke volume (SV) contributes to the increase in cardiac output that occurs when cardiac transplant patients (CT) exercise between 50% and 75% of maximum. Upright arm and leg exercise was performed by 13 CT and 10 normal controls. Cardiac output (CO2 rebreathing), expired air, and catecholamine measures were obtained at rest and at 50% and 75% of maximum. From rest to 50% of maximum both normals and CT increased heart rate (HR) and SV during arm and leg exercise. In normals, HR (arm = +17 +/- 2 min-1; leg = +21 +/- 3 min-1) was increased further at 75% of maximum but not SV (arm = 3 +/- 4 ml; leg = +2 +/- 8 ml). In CT, further increases in both HR (arm = +9 +/- 1 min-1; leg = +13 +/- 1 min-1) and SV (arm = +12 +/- 5 ml; leg = +12 +/- 3 ml) were observed at 75% of maximum. During leg exercise plasma norepinephrine was increased more in CT than in normals. Between 50% and 75% of maximum, an increase in SV is a more important mechanism for increasing cardiac output during upright arm and leg exercise in CT than in normals. PMID- 8201897 TI - Relationship between cardiorespiratory fitness and lipoprotein(a) in men and women. AB - Lipoprotein(a) [Lp(a)] is a distinct lipoprotein of the low density lipoprotein (LDL) class. Research has shown that elevated Lp(a) is an independent risk factor for coronary heart disease (CHD). The purpose of this cross-sectional study was to determine whether fitness was associated with Lp(a) concentrations. Cardiorespiratory (CR) fitness, assessed by maximal treadmill time, percent body fat (hydrodensitometry), body fat distribution (waist/hip ratio), lipoprotein profile and LDL particle size (2-16% gel electrophoresis) were determined in healthy Caucasian men (N = 100) and women (N = 50). As expected, the frequency distribution of Lp(a) was highly skewed with a mean level of 16.9 +/- 19.1 mg.dl 1 (range 0.10-90 mg.dl-1) for men and women combined. Lp(a) was only significantly (P < 0.05) correlated with cholesterol (r = 0.29) in women and LDL C (r = 0.22) in men. However, after correcting LDL-C for Lp(a) content, the correlation was not significant (r = 0.06). A MANCOVA, controlling for age, across highest and lowest CR fitness quartiles suggest a typical positive influence of improved CR fitness on lipoproteins, body composition, and fat distribution; however, Lp(a) levels were not affected. These data indicate that there is no direct association between plasma Lp(a) and body composition, fat distribution, or CR fitness in healthy men and women. PMID- 8201898 TI - Skeletal muscle weakness in old age: underlying mechanisms. AB - Maintenance of muscle mass and strength contributes to mobility which impacts on quality of life. Although muscle atrophy, declining strength, and physical frailty are generally accepted as inevitable concomitants of aging, the causes are unknown. Clarification of the mechanisms responsible for these changes would enhance our understanding of the degree to which they are preventable or treatable. The decline in muscle function between maturity and old age is similar for muscles of many different animals including human beings, and is typified by the decreases of approximately 35% in maximum force, approximately 30% in maximum power, and 20% in normalized force (kN.m-2) and power (W.kg-1) of extensor digitorum longus (EDL) muscles in old compared with adult mice. Much of the age associated muscle atrophy and declining strength may be explained by motor unit remodeling which appears to occur by selective denervation of muscle fibers with reinnervation by axonal sprouting from an adjacent innervated unit. Muscles in old mice appear more susceptible to injury than muscles in young or adult mice and have a decreased capacity for recovery. The process of age-related denervation may be aggravated by an increased susceptibility of muscles in old animals to contraction-induced injury coupled with impaired capacity for regeneration. PMID- 8201899 TI - Exercise on-transient gas exchange kinetics are slowed as a function of age. AB - The purpose was to characterize gas exchange kinetics following the on-transient of exercise in men aged 30-80 yr. Forty-six men completed square wave exercise tests from loadless cycling to subventilatory threshold (V(E)T) work rates with gas exchange measured breath-by-breath. Signal averaged data were fit with a monoexponential equation to derive time constants (tau) for gas exchange and ventilation (tau VO2, tau VCO2, tau VE) and heart rate (tau HR). There was a significant slowing of ventilation and gas exchange kinetics across age with linear regression yielding an increase of 0.67 s.yr-1 for tau VO2 (39 s in young to 61 s in old), 0.57 s.yr-1 for tau VCO2, and 0.65 s.yr-1 for tau VE, whereas tau HR (44 to 41 s) was not changed significantly. The slowed VO2 kinetics with age may reflect limitations in muscle blood flow or in control of the rate of oxidative metabolism. The less marked slowing of tau VCO2 compared with tau VO2 across age may reflect reduced CO2 storage capacity with loss of muscle tissue. The tau VE change across age was similar to that for tau VCO2 (tau VE/tau VCO2 unchanged). The present study demonstrated marked age-related slowing of gas exchange dynamics at exercise onset. PMID- 8201900 TI - Effects of aerobic endurance training on gas exchange kinetics of older men. AB - The kinetics of gas exchange at the on-transient of exercise are appreciably slowed in older individuals. Eight older men (72 yr) completed 6 months of aerobic cycle training. Ventilation and gas exchange kinetics were determined at the onset of a below threshold (ventilatory threshold, V(E)T) square wave exercise function and compared with control values (N = 4, age 70 yr). Gas exchange data were measured breath-by-breath and signal averaged data were fit with a monoexponential function to determine the time constants (tau). The training group showed significant increases in VO2max (20%) and VO2 at V(E)T (21%). The tau for oxygen uptake kinetics decreased significantly (62.2 +/- 15.5 to 31.9 +/- 7.0 s). The tau VCO2 (70.9 +/- 10.9 to 43.8 +/- 11.4 s) and tau VE (89.2 +/- 18.0 to 50.4 +/- 11.3) also were significantly faster posttraining; however, tau HR (38.1 +/- 20.5 to 28.6 +/- 7.2) was not significantly altered. Thus, with a vigorous training program, the kinetics of gas exchange of older individuals were faster, and approached values reported in fit young subjects. PMID- 8201901 TI - Effects of caffeine on the metabolic and catecholamine responses to exercise in 5 and 28 degrees C. AB - The influence of caffeine on the metabolic and catecholamine responses to mild exercise in a cold and a warm environment was studied in eight healthy males. The subjects performed 60 min of cycling at 50% VO2max in a cold environment (5 degrees C and 70% relative humidity) and a warm environment (28 degrees C and 50% relative humidity) 30 min after ingesting caffeine (5 mg.kg-1 body weight) or placebo (dextrose). Caffeine ingestion prior to exercise in the warm environment resulted in increased plasma epinephrine, with no effect on plasma norepinephrine. Neither lipid nor carbohydrate metabolism was altered by caffeine in the warm trial. Exercise in the cold environment (placebo) produced increased VO2 and carbohydrate metabolism, decreased lipid metabolism, and no difference in plasma catecholamines compared with the warm-placebo trial. Responses to the combination of caffeine ingestion and the cold environment did not differ from cold-placebo responses in VO2 during the cycling bout. However, in the cold caffeine trial plasma epinephrine was elevated. In addition, fat oxidation and serum free fatty acids were elevated in the cold-caffeine condition. Carbohydrate oxidation was depressed, while serum glucose and blood lactate were elevated in this trial compared to cold-placebo. Thus, caffeine increases plasma epinephrine; cold increases oxygen consumption and carbohydrate metabolism, while decreasing lipid metabolism; and the combination of caffeine and cold during exercise increases plasma epinephrine and lipid metabolism, but decreases carbohydrate metabolism. PMID- 8201902 TI - Vagal afferents reflexly inhibit exercise in conscious rats. AB - Activation of vagal afferents reflexly inhibited locomotion induced by stimulation of the mesencephalic locomotor region in decerebrate cats. However, this reflex has not been tested in intact mammals. Therefore, the purpose of this study was to test the hypothesis that vagal afferent stimulation would inhibit somatomotor activity in the intact conscious rat. Six Sprague-Dawley rats were chronically instrumented with carotid arterial and femoral venous catheters and electromyogram (EMG) electrodes inserted into the biceps femoris muscle. Cardiac autonomic efferent blockade [atropine methyl bromide (14 mg.kg-1, i.v.) and metoprolol (14 mg.kg-1, i.v.)] and alpha-adrenergic receptor blockade [phenoxybenzamine (5 mg.kg-1, i.v.)] was achieved to prevent bradycardia and hypotension. Vagal afferents were stimulated (phenyl-biguanide 2.5 and 5.0 micrograms.kg-1 i.v.) during steady state exercise (9.0 m.min-1, 10% grade). Phenyl-biguanide decreased exercise EMG activity 30 +/- 6% and 54 +/- 10% in a dose dependent manner without significantly altering mean arterial pressure or heart rate. We speculate that this reflex may serve as a negative feedback mechanism to indirectly reduce myocardial oxygen demands during exercise. PMID- 8201903 TI - The effect of lower body positive pressure on the exercise capacity of individuals with spinal cord injury. AB - The purpose of this study was to determine the effect lower body positive pressure (LBPP) has on the cardiovascular/exercise capacities of individuals with spinal cord injury (SCI) during both arm crank exercise (ACE) and wheelchair exercise performed on a treadmill (WCTM). Ten male adults (age = 31.1 +/- 10 yr) with SCI and five male nondisabled (ND) adults (31.2 +/- 10 yr) participated in this study. The ND subjects performed ACE only. For subjects with SCI, significantly higher (P < 0.025) peak VO2 (1042 +/- 212 vs 839 +/- 218 ml.min-1), peak VE (46 +/- 17 vs 35 +/- 9 l.min-1), and work rate (50 +/- 15 vs 40 +/- 13 W) were seen during ACE with LBPP. No significant differences for peak VO2, VE, or work rate were seen for the ND subjects with LBPP during ACE. In addition, significantly higher peak VO2 (960 +/- 322 vs 828 +/- 312 ml.min-1) was recorded with LBPP for the subjects with SCI during WCTM. Cardiac output (Q, l.min-1; CO2 rebreathing method) was measured at 50% peak VO2 for both ND subjects and subjects with SCI during ACE. Subjects with SCI demonstrated significantly higher SV (94 +/- 20 vs 84 +/- 20 ml) with LBPP. No differences were observed in SV at 50% peak VO2 during ACE for the ND subjects with LBPP. The results of this study suggest that for individuals with SCI, LBPP augments exercise capacity by preventing the redistribution of blood to the lower extremities. PMID- 8201904 TI - Goal setting and performance in sport and exercise settings: a synthesis and critique. AB - Although goal setting research in industrial and organizational settings has been proliferating rapidly over the past 20 yr, it is only recently that sport psychologists begun to systematically test its effects in sport and exercise settings. However, the recent empirical literature in sport and exercise examining the relationship between goals and performance has been equivocal. Thus, the purposes of the present review are fourfold: (a) briefly review the industrial/organizational literatures concerning the relationship between goals and task performance; (b) review the literature testing the relationship between goals and performance in sport and exercise settings; (c) discuss methodological and interpretive limitations including the impact of mediating variables; (d) offer future directions for research. PMID- 8201905 TI - Psychological skills for enhancing performance: arousal regulation strategies. AB - This review summarizes and integrates current empirical and theoretical research on arousal regulation strategies for enhancing athletic performance. The need to view arousal as a multifaceted construct made up of both cognitive and physiological components was emphasized, as well as the importance of understanding arousal-performance relationship theories that go beyond a simple inverted-U notion. Categories of arousal regulation strategies were discussed and included: arousal energizing techniques, biofeedback techniques, relaxation response strategies, cognitive behavioral interventions, and mental preparation routines. It was concluded that these techniques can be effective in influencing arousal and facilitating performance. However, additional research (especially evaluation research) using more rigorous methods, determining how and why interventions work, using case study methodologies, identifying personality and situational factors influencing arousal regulation effectiveness, and identifying the most effective means of teaching arousal regulation is needed. PMID- 8201906 TI - Imagery interventions in sport. AB - The use of imagery processes in the regulation and enhancement of sports performance is examined in this review paper. Research studies in this area are reviewed and four general categories of research are identified: 1) mental practice, 2) precompetition imagery, 3) comparisons of successful and unsuccessful competitors, and 4) mediating variables. The conclusion is reached that mental practice research has produced equivocal results and the reasons for this are examined. The argument is made that the mental practice model for research into imagery processes in sports is nonproductive. Suggestions for future research directions are offered and guidelines for productive imagery research in sport are provided. PMID- 8201907 TI - Current status and prominent issues in sport psychology interventions. AB - The prospect of human psycho-behavioral change has fueled the development and growth of applied sport psychology and psychological intervention with athletes. The purpose of this review is to examine the current status of sport psychology interventions and identify issues related to psychological intervention in sport. The development of sport psychology in North America is overviewed and issues arising from the emergence of applied sport psychology are identified. Sport psychology intervention research is reviewed and it is concluded that the effectiveness of sport psychology interventions is supported in the literature. Problems in intervention research are identified and future directions for sport psychology are suggested. These suggestions include a science-practice integration, the use of idiographic assessment methods, the identification and control of moderator variables, and the contextualization of interventions within the unique environment of sport. PMID- 8201908 TI - Neuromuscular adaptations following prepubescent strength training. AB - Underlying mechanisms of prepubescent strength gains following resistance training are speculative. The purpose of this investigation was to determine the effects of 8 wk of resistance training on muscular strength, integrated EMG amplitude (IEMG), and arm anthropometrics of prepubescent youth. Sixteen subjects (8 males, 8 females) were randomly assigned to trained or control groups. All subjects (mean age = 10.3 yr) were of prepubertal status according to the criteria of Tanner. The trained group performed three sets (7-11 repetitions) of bicep curls with dumbbells three times per week for 8 wk. Pre- and posttraining measurements included isotonic and isokinetic strength of the elbow flexors, arm anthropometrics, and IEMG of the biceps brachii. Planned comparisons for a 2 x 2 (group by test) ANOVA model were used for data analysis. Significant isotonic (22.6%) and isokinetic (27.8%) strength gains were observed in the trained group without corresponding changes in arm circumference or skinfolds. The IEMG amplitude increased 16.8% (P < 0.05). The control group did not demonstrate any significant changes in the parameters measured. Early gains in muscular strength resulting from resistance training prepubescent children may be attributed to increased muscle activation. PMID- 8201909 TI - Effect of body build on weight-training-induced adaptations in body composition and muscular strength. AB - The aim of the present study was to investigate whether weight-training-induced adaptations in body composition and isokinetic strength differ as a function of body build. Body build of a subject was characterized as the extent to which a person's fat-free mass index (FFMI = fat-free mass.height-2;kg.m-2) differs from the regression of FFMI over fat mass index (FMI = fat mass.height-2;kg.m-2) as derived from a sedentary male population (N = 77). From this population two groups with either a slender (N = 10) or a solid (N = 11) body build were selected. For 12 wk the subjects performed a weight-training program twice a week. Training induced a significant (P < 0.05) increase in fat-free mass (FFM) in the solid group (1.6 kg, 2.3%) in contrast with the slender group, which showed no significant change in FFM. Both groups showed comparable decreases in fat mass (FM; slender: -1.7 kg, -10.8% versus solid: -2.4 kg, -11.3%) and increases in strength (on average 13.8%). In conclusion, the increase in FFM due to a weight-training program is modified by body build. This modification, however, is restricted to a larger increase in the solidly built group. PMID- 8201911 TI - Ultrastructural study of cell injury induced by coxsackievirus B3 in pancreatic and cardiac tissues. AB - Balb/c weanling mice were intraperitoneally inoculated with a myocarditic variant of coxsackievirus B3, with the aim of characterizing more thoroughly the features of virus-induced cell injury in pancreas and heart, as well as to compare ultrastructural alterations with histological and virological findings. During the first week post-infection (pi), all animals developed acinar pancreatitis, followed by focal myocarditis. At electron microscopy, acinar cells showed patent distortion, including marked loss of organelles and zymogen granules, together with gross dilatation of rough endoplasmic reticulum. Cardiac cells presented severe cytoskeletal changes, as myofibrillar collapse with a haphazard arrangement, concomitant with a decrease in myofibril number; besides, irregular pattern of nuclear chromatin and increased presence of swollen mitochondria were often observed. As the few initially detected lymphocytes tended to disappear in necrotic foci, there was an increase in fibroblast number concurrent with progressive scarring. Ultrastructural changes in both pancreas and heart correlated with local viral replication, suggesting that cell damage is attributable to direct viral action. PMID- 8201910 TI - [Enteropathogenic microorganisms in children with acute diarrhea in 2 hospitals of Rosario, Argentina]. AB - As part of a multicenter collaborative study the relative frequency of enteropathogenic agents in children less than 5 years of age with acute diarrhea was determined. Rates of isolation were similar as regards sex, age, and season. The frequency of polymorphonuclear cells (PMN) in the stools was significantly higher among patients requiring admission in comparison with ambulatory patients. Enteropathogenic E. coli (EPEC) was isolated more frequently in that group in comparison with outpatients (p < 0.001), mainly among children less than 5 months of age. The most prevalent agents were EPEC (26.1%), enterotoxigenic E. coli (ETEC) (9.7%), Shigella (8.5%), Rotavirus (5.1%), Giardia (3.6%), Campylobacter (3.2%), and Salmonella (2.4%). The EPEC predominant serogroups were 0 111, 0 55, 0 26, and 0 119. ETEC serotypes 0 153:H45 and 0 128:H21 were more often isolated. The predominant species in the genus Shigella were S. flexneri (80.5%), and S. sonnei (9.5%); in the genus Campylobacter, the species were C. jejuni (81.3%), and C. coli (18.7%). Shigella was clearly related to the presence of PMN in the faeces, in children less than 5 months old. Campylobacter was more frequent in ambulatory patients more than one year of age. Rotavirus was found predominantly in autumn and winter. Salmonella and ETEC were more frequent in summer. Giardia was associated with weight loss. In about 10% of the cases there were simultaneous mixed isolations of two or more agents. Salmonella isolates were sensitive to the majority of antimicrobial agents probed. Many Shigella and E. coli were resistant to sulfamethoxazole-trimethoprim and ampicillin (40-80%). Nearly all enterobacteria were sensitive to gentamicin and norfloxacin. PMID- 8201912 TI - [Diclofenac vs nimesulide in arthrosis. Plasma levels and clinical efficacy]. AB - Diclofenac and nimesulide are non-steroidal antiinflammatory agents advocated for use in painful and inflammatory rheumatic and certain non rheumatic conditions. In Uruguay, these drugs are administered in doses of 100 mg and 200 mg once a day, respectively. Diclofenac is an effective and safe analgesic and antiinflammatory drug. There are scarce data available on the pharmacokinetic profile of nimesulide. These facts encouraged us to undertake the present study on clinical efficacy, tolerance and pharmacokinetics of nimesulide, controlled with sustained release diclofenac. Twenty patients with osteoarthritis, stage II III, according to a clinical-radiological evaluation, were selected for the study. Patients were assigned at random to treatment A (Voltaren sustained release, 100 mg) or B (Nodo regular formulation, 200 mg) once a day. A double blind study with active drug and controlled parallel groups was designed. After a washout period of one week patients were treated with active medication during 84 days, and clinical controls every 14 days ensued. Experienced rheumatologists assessed pain and other clinical symptoms. Blood samples were drawn on days 7, 49 and 91 of the study, ten hours after the morning dose, and plasma diclofenac and nimesulide concentrations were measured. On day 7 and 91, blood counts and biochemical laboratory studies were performed (namely, hemoglobin, RBC, WBC, leucocyte differential count, platelet count, alkaline phosphatase, ASAT, ALAT, creatinine, etc.) Already two weeks after the study had begun, significant improvements in clinical parameters assessed were seen for both treatments. A trend to accumulation of diclofenac and nimesulide along the three months of treatment was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201913 TI - [Nutritional status of vitamin D in mothers and neonates of Ushuaia and Buenos Aires]. AB - Serum levels of calcium, phosphorus, total alkaline phosphatase (AP) and 25 hydroxyvitamin D (250HD) were measured at the end of the winter in Group 1 (Ushuaia, latitude 55 degrees S): 16 women (24-48 hs postpartum serum blood) and 20 neonates (cord blood) and in Group 2 (Buenos Aires, latitude 34 degrees S) 21 women (24-48 hs postpartum serum blood) and their 21 neonates (cord blood). The neonatal serum calcium and phosphorus were higher and the neonatal serum AP and 250HD level were lower than maternal levels in both groups (Table 1 and 2). Serum levels of 250HD were diminished (< 8 ng/ml) in 62% of the mothers and 81% of the neonates of Ushuaia and in 24% of the mothers and 16% of the neonates of Buenos Aires (figure 1). Neonatal serum 250HD levels correlate with maternal serum 250HD levels in the paired group of Buenos Aires (r = 0.65, p < 0.003) (Figure 2). In Ushuaia the serum 250HD levels (X +/- SD) in neonates (3.9 +/- 2.7 ng/ml) and in mothers (6.3 +/- 4.8 ng/ml) were lower than in Buenos Aires (neonates: 11.3 +/- 6.0 ng/ml and mothers: 14.4 +/- 8.4 ng/ml, p < 0.001). Maternal serum calcium levels were lower in Ushuaia (8.7 +/- 0.8 mg/dl) than in Buenos Aires (9.2 +/- 0.4 mg/dl) (p < 0.05). In conclusion, 1) In Ushuaia pregnant women and their neonates had a deficient nutritional state of vitamin D. Preventive administration of vitamin D would probably be beneficial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201914 TI - Environmental effects on cardiovascular reactivity. AB - The hypothesis on which this paper is based states that the environment where subjects live has a modifying effect on their psychophysic reactivity when faced with unknown stressing stimuli. To prove such hypothesis, subjects of an isolated country village were studied. An urban sample was used as control. Vascular reactivity was used to determine psychophysics reactivity. Both groups were submitted in their respective environments to a standardized conflicting stimulus which was produced by a device developed in our laboratory. The variables of cardiovascular reactivity were systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). Paired samples by age and basal SBP were used (N = 24 pairs). The results of this experience showed that city dwellers had significantly higher SBP increments than country dwellers. After discussing different variables that may have accounted for these results, it was concluded that city life increases the psychophysics reactivity of city dwellers when faced with stressing stimuli as compared to country dwellers. PMID- 8201915 TI - Chronic indomethacin administration and its relation with the renal kallikrein kinin system during rat pregnancy. AB - The main purpose of the present study was to elucidate the potential role of vasodilator prostaglandins and the kallikrein kinin system in renal hemodynamic changes observed during rat gestation. Nineteen pregnant rats, un-treated and treated with Indomethacin (3 mg/kg body/wt) for 4 days during peak glomerular hyperfiltration, were studied before and during pregnancy. Twenty-two non pregnant rats were also included as controls. Daily urinary volume, electrolytes and kallikrein excretion and creatinine clearance were measured along the experiment. Baseline creatinine clearance increased by 43% at the beginning of the third week of pregnancy to decline thereafter. Urinary kallikrein rose earlier, at the second week of pregnancy, and decreased near term while at the same time sodium excretion dropped by 30%. Indomethacin treatment prevented both the maximum increment in glomerular filtration rate occurring in normal pregnancy between days 14 to 18 and the physiological near term decline in kallikrein excretion. Furthermore, it induced an increase in sodium excretion in late pregnancy. These results suggest that vasodilator prostaglandins and the kallikrein kinin system may well participate in gestational hyperfiltration and sodium homeostasis of pregnant rats. PMID- 8201916 TI - [Houssay's phenomenon in man]. AB - The phenomenon of clinical improvement of diabetes mellitus after occurrence of pituitary insufficiency has been reported occasionally in the medical literature, as a human counterpart of Houssay's experiment with hypophysectomized diabetic animals. We report the case of a 76-year-old woman who developed diabetes in 1928, at the age of 14, and was treated with low doses of insulin. At the age of 29, during the 7th month of her second pregnancy, she suddenly developed severe headaches and soon afterwards an intense polyuria which subsided under treatment with posterior pituitary extract. Her pregnancy followed to term but uterine stimulants had to be used at delivery because of lack of contractions. She was unable to nurse her baby and a permanent amenorrhea ensued. She continued using the posterior pituitary powder for several years, after which she discontinued it without adverse effects. The dose of insulin was decreased gradually until its replacement by chloropropamide in 1967 and glibenclamide in 1970. The present dose of glibenclamide is 2.5 mg daily, on which she has occasional mild hypoglycemic reactions. When the medication was discontinued for 5 days glycemia rose to 450 mg/dl but responded immediately to 2.5 mg of the drug with a mild hypoglycemia. She never required thyroid hormone therapy. Glucocorticoid substitution was instituted recently because of evidence of mild adrenocortical insufficiency. Basal hormone levels were normal for thyroxin, thyrotropin, FSH, LH, prolactin, hGH and cortisol; the responses to pituitary stimulation with TRH and LHRH were subnormal or nil. Cortisol stimulation with ACTH was normal. Insulin levels rose moderately after stimulation with glucagon, and with glibenclamide, with simultaneous marked decrease in glycemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201917 TI - [Arterial hypertension, heart failure, chronic bronchitis]. PMID- 8201918 TI - [Causes of CO2 retention in patients with chronic obstructive lung disease]. AB - The mechanisms of chronic ventilatory failure in chronic obstructive pulmonary disease are complex. This paper analyses the diverse available information: mechanical factors and gas-exchange, fighter vs. non-fighter, the ventilatory pattern theory and the fatigue threshold theory. Finally we comment on the evidence supporting the new concept that hypercapnia may develop to avoid or prevent fatigue. Indeed, it is very likely that chronic CO2 retention in COPD may develop by mechanical disadvantages of the inspiratory muscles rather than impairment of ventilation-perfusion ratios. This opens a fascinating new research line on the neuromechanical control of breathing. When the respiratory effort is approaching the fatigue level, the respiratory muscles may elicit a negative feedback reflex, the muscle activity is depressed and hypercapnia develops. If this is so, chronic hypercapnia may be an index of imminent fatigue if increases in ventilation or work of breathing are required. Under this condition some degree of central diaphragm fatigue may help to protect the muscle from severe or limiting peripheral fatigue or even muscle injury. Finally, we comment on some therapeutic approaches such as ventilatory stimulants, training, rest and, specially, oxygen administration and the mechanisms involved in the PCO2 increases. PMID- 8201919 TI - [Integrins: a family of cell adhesion receptors]. AB - Integrins are a family of cell adhesion molecules (CAM's) that mediate the communication between the intracellular and the extracellular compartments. The growing interest in CAM's is due to the essential role they play in cell-cell and cell-matrix recognition processes. These receptors are formed by a non-covalently associated glycoprotein complex of two distinct polypeptide chains, called, alpha and beta. The association of different subunits results in the formation of, at least, 16 different integrins that provide cells with a great versatility in their adhesion properties. An integrin molecule comprises a cytoplasmic domain that interacts with the cytoskeleton, a transmembranous domain and an extracellular domain that binds to one or more ligands. beta 1, beta 2 and beta 3, are the best characterized integrin subfamilies; they are expressed, in different amounts, in epithelial and endothelial cells, leukocytes, fibroblasts and platelets. b1 integrins are essentially involved in cell-extracellular matrix interactions and beta 2 subfamily in leukocyte-leukocyte and leukocyte endothelial cell communications. The integrin subfamily beta 3 mediates the adhesion of platelets with fibrinogen and other ligands. During embryonic development, integrins in association with other CAM's, play an essential role in cell migration and morphogenesis. Moreover, in processes like inflammation, wound healing and thrombosis, integrins and other CAM's mediate the interactions among the injured tissue and circulating cells. In two genetic diseases like the leukocyte adhesion deficiency and the Glanzmann's thrombasthenia an impairment in leukocyte-endothelial cell interactions and platelet aggregation is detected, due to deficiencies or abnormalities in beta 2 or beta 3 integrin subfamilies, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201920 TI - [Postmenopause, plasma lipoproteins, and hormone replacement therapy]. AB - The incidence of coronary heart disease (CHD) rises after menopause. Hormonal replacement therapy (HRT) reduces cardiovascular morbidity and mortality. Plasma lipoproteins are modified by oral estrogen treatment: LDL are lowered while HDL and VLDL are augmented. The cardioprotective effect of oral HRT may be partially due to the reduction in the LDL/HDL ratio. Optimal changes in lipid profile are achieved with doses that usually prevent bone mass loss. Progestogens tend to blunt the increment of HDL induced by estrogens, but this depends on the type of agent and its dose. Unlike oral estrogen, HRT by the transdermal route does not always modify the lipid profile. When it does, changes are similar to those observed under the oral route in that the LDL/HDL ratio is diminished, but VLDL do not rise. Possible explanations for this discrepancy are discussed. At present there is no clear evidence that combined estrogen/progestogen treatment or transdermal estrogen alone could reduce CHD's incidence. Women with an intact uterus should receive a progestogen in addition to estrogen for prevention of endometrial carcinoma. Estrogen alone is preferable for hysterectomized women. When beneficial and adverse effects of HRT are considered simultaneously, the overall result is considered favorable, principally as a consequence of its cardioprotective properties. PMID- 8201921 TI - [Health protection: drugs and food]. PMID- 8201922 TI - [Transgenic animals in biomedicine]. PMID- 8201923 TI - [Minimally invasive diagnostic and therapeutic procedures]. PMID- 8201924 TI - [Cutaneous-visceral loxoscelism, acute tubular necrosis, and arregenerative anemia]. PMID- 8201925 TI - [Short-term prognosis in patients with congestive heart failure and normal left ventricular systolic function]. AB - Congestive heart failure (CHF) has been traditionally associated with impairment of the left ventricular systolic function (LVSF). There are few clinical assays that describe the prognosis of patients with CHF and intact LVSF. The aims of this prospective assay are: to describe a group of 70 patients admitted to an internal medicine department with the clinical syndrome of CHF, to determine the contractile state of the left ventricle with echocardiography and to establish the short term prognosis. There were 39 males and 31 females with a mean age of 76.4. The LVSF was impaired in 38 (54.3%) [Group I] and preserved in 32 (45.7%) [Group II] (Table 1). Sex distribution was different between both groups with women predominating in group II (Figure 1). Fourteen patients belonging to Group II had diastolic function impairment according to cardiac Doppler. There was no other evidence of cardiac abnormality that could justify CHF. During an average of 8 months follow-up 20 (28%) patients died. There were no differences in overall mortality between Groups I and II (Figure 2). Multivariate analysis was used to determine the relative risk in prognosis of the covariates age, gender, systolic function and diameters of the LV. None of these were statistically significant (Table 2). In our series 45.7% of the patients with CHF had normal LVSF. The short term prognosis proved to be the same in patients with and without impaired LVSF. PMID- 8201926 TI - [Spinal arachnoiditis as a complication of peridural anesthesia]. AB - Seven patients who received epidural anesthesia for gynecological (5 cases), cosmetic (1 case) or general surgery (1 case) developed spinal arachnoiditis leading to subarachnoid cyst in all 7 and cord cavitation in 5. MRI was useful to show the subarachnoid and intramedullary cysts, as well as to monitor lesion extent and progress. Associated MRI findings were a Chiari anomaly in one case, a tethered cord in another and spinal cord atrophy in a third. One patient refused surgery but improved spontaneously while the other six were treated by a shunting procedure, with a satisfactory outcome in three. Meningeal inflammation may have left scars which later induced ischemia and subsequent cavitation. Alternatively, CSF circulation blockade may have dilated the central spinal canal causing ischemia by compression, followed by myelomalacia and cavitation. Careful handling of this procedure is urged in order to avoid such severe complications. PMID- 8201927 TI - [Spontaneous splenic hypofunction in systemic lupus erythematosus and primary Sjogren syndrome]. AB - The objective of this study was to evaluate hyposplenism in autoimmune diseases by the presence of Howell-Jolly bodies in blood erythrocytes and 99Tc spleen scan. Blood smears of 174 patients with autoimmune diseases and 126 controls were studied. Other possible causes for the presence of Howell-Jolly bodies were excluded. Evidence of hyposplenism was demonstrated in 4 of 79 patients with Systemic Lupus Erythematosus (SLE) and in 2 of 18 cases of primary Sjogren Syndrome (PSS), whereas no hyposplenism was found in the remaining cases of other autoimmune diseases. In one of the patients with SLE, hyposplenism was transient. Among the control cases, a patient with Chronic Lymphocytic Leukemia with splenomegaly presented hyposplenism. IN CONCLUSION: 1) Hyposplenism is more frequently found in SLE and PSS than in other autoimmune diseases. 2) Hyposplenism in autoimmune diseases can be transient. 3) Splenomegaly and enlarged spleen scan do not exclude hyposplenism. PMID- 8201928 TI - [Prophylaxis with fluoroquinolones in patients with neutropenia]. AB - In order to evaluate whether the prophylactic use of fluoroquinolones diminishes the incidence of infections and/or mortality during neutropenia, we undertook a prospective, aleatory and controlled study in non-hospitalized adult patients with acute leukemia and chemotherapy-induced neutropenia including twenty five episodes of neutropenia including twenty five episodes of neutropenia which had occurred in 14 patients who were randomly selected either to receive or not quinolones (norfloxacin 800 mg daily or ciprofloxacin 1000 mg daily). Both groups were similar in terms of sex, age, underlying disease, chemotherapy for hematologic malignancy, duration and severity of neutropenia. The use of quinolones was associated with a delay in the fever onset during neutropenia (p = 0.0448), a decrease in the proportion of neutropenic febrile days (p = 0.0456), a decrease of infections caused by gram-negative bacilli (p = 0.037) and an increase of Streptococcus infections (p = 0.0857). There was no significant decrease in mortality, incidence of severe infections, proportion of neutropenic episodes without fever, empiric use of amphotericin B or fungal infections between both groups. The results of this study demonstrate that the prophylactic use of fluoroquinolones does not diminish the infectious morbidity and/or mortality in these patients. PMID- 8201929 TI - Marmosets in New World leishmaniasis research. AB - In leishmaniasis, the search for a suitable experimental animal model is highly recommended, especially in Leishmania (Viannia) braziliensis (L. (V) b) research. Diverse species of neotropical primates have increasingly been used as experimental hosts of Leishmania. This article describes aspects of parasite L(V)b and marmoset, Callithrix penicillata (Primates, Callithricidae), interaction and summarizes the biology of parasitism in this primate model. Results of recent studies on primary infections with several strains of L(V)b as well as parasitism evolution, clinical outcome patterns and immunoprotection experiments, are summarily discussed. The relevance of homologous reinfection experiments for vaccine development in leishmaniasis is discussed. PMID- 8201930 TI - [Polyarthritis, intestinal necrosis, livedo reticularis, polyneuropathy, and purpura]. PMID- 8201931 TI - [Utero-vaginal duplication with hematocolpus. Diagnosis by magnetic resonance imaging (MRI)]. AB - A 21-year-old woman with complete uterus-vaginal duplication, hemivaginal obstruction and ipsilateral renal agenesis is presented. Ultrasonography shows uterus duplication with a parauterine cystic mass. MRI demonstrated uterus duplication and also a para/infra uterine mass with T1 and T2 weighted high signal-intensity disclosing its serohematic nature. Surgical procedure confirmed the MRI findings. PMID- 8201932 TI - [Seropositive polyarthritis as a presentation form of angioimmunoblastic lymphadenopathy]. AB - We present a 59-year-old male who was admitted due to fever and generalized lymphadenopathy. The patient had polyclonal hypergammaglobulinemia, Coombs positive anemia, positive rheumatoid factor (latex 1:1280-SCAT 1:128), hypocomplementemia, negative LE cells and FAN negative. He had a 2 months history of a rheumatoid arthritis-like polyarthritis with poor response to non-steroid antiinflammatory drugs. On physical examination a mild symmetrical polyarthritis of small and large joints was seen. A lymph node biopsy showed architectural effacement, absence of germinal centers, arborization of postcapillary venules and a polymorphonuclear infiltrate that included immunoblasts. Thus, this patient fulfills the morphologic criteria of angioimmunoblastic lymphadenopathy (AILD) (Fig. 1 and 2). Our purpose was to describe the association of seropositive polyarthritis with AILD as a presentation sign. Whether this represents a case of a rheumatoid arthritis with AILD or the polyarthritis which has been described as part of the clinical picture or AILD is difficult to say due to the short time evolution of the disease. PMID- 8201933 TI - [Atheroembolism]. AB - The observation of the eye-ground allows the recognition of atheromatous emboli within the arterial lumen and some of the characteristics of the evolution of such an accident. An analogy is drawn with pathological observations and clinical findings. The increased use of arterial invasive diagnostic and therapeutic procedures has increased the chances of producing atheroembolism giving the opportunity of observing its pathological and clinical consequences. We comment on the factors that could explain the lack of recognition and demonstration of cholesterol embolism. Lack of awareness is still the main factor. PMID- 8201934 TI - [Energetics of ionic behavior in heart muscle contraction. Physiologic and physiopathologic aspects]. AB - It is widely accepted that the ionic movement across the different membrane systems (i.e. sarcolemma, sarcoplasmic reticulum, mitochondria), plays a major role on heart muscle metabolism. On the other hand, neither the relative role nor the associated energy expenditure of those mechanisms have been definitively established. Biochemical and biophysical measurements of the different ion exchange mechanisms, have provided data leading to the postulation of different models for both resting and active metabolism of the heart muscle. The present work analyzes, from an energetic standpoint, available biochemical and biophysical data from the literature calculating the range of energy expenditure that should be attributable to each mechanism. Sodium, potassium and calcium movements during either resting and/or active state are particularly analyzed and the fractional role of various organelles (sarcolemma, sarcoplasmic reticulum and mitochondria) discussed. From this analysis and the known amount of energy released (or the amount of oxygen consumed) by the muscle it is possible to determine whether there is enough energy for a given model of ionic exchange during the excitation contraction process. In addition to this analysis a comparatively short review of energetic studies performed under pathological conditions is also presented. In particular, the pathological conditions analyzed are those with an energetic compromise such as heart hypertrophy, ischemia and anoxia in which the alteration of ionic transport mechanisms seems to be playing a major role. PMID- 8201935 TI - [New perspectives in calcium metabolism]. AB - Although Ca in small quantities plays a fundamental role in cell activation, excessive intracellular Ca accumulation results in severe cellular damage and is a major factor in the pathophysiology of multiple diseases. Paradoxically, high Ca intake may be beneficial in unrelated disorders such as arterial hypertension, nephrolithiasis and in the prevention of colon cancer. Parathyroid hormone (PTH) could be the link capable to explain this paradox. PTH stimulates cellular calcium influx. Under normal conditions, this effect takes place only in target tissues for the hormone, but in the presence of altered cell-membrane permeability for calcium, normal plasma PTH may be detrimental, enhancing cellular calcium influx. Thus, the suppression of PTH secretion by a high Ca intake would result in a reduced PTH-induced cellular Ca accumulation in genetically predisposed tissues with a loose cellular Ca control. Thus, parathyroid ablation in dystrophic hamster reduces the elevated muscle Ca observed in muscular dystrophy and causes histological improvement without altering the serum Ca concentration. The amount of dietary Ca required is not firmly established, but anthropological observations suggest a daily intake of approximately 1600 mg, much higher than the present average Ca intake in Western societies. Thus, a higher Ca intake would be beneficial in the treatment, and more importantly, in the prevention of multiple diseases. PMID- 8201936 TI - [Various unsolved questions on osteoporosis]. PMID- 8201937 TI - [The impact of retrovirus on oncoimmunology: from oncogenes to superantigens]. PMID- 8201938 TI - [Moyamoya disease and Down syndrome]. PMID- 8201939 TI - [Antigenemia and CD4+ cell count in HIV-1 infected patients]. PMID- 8201940 TI - [Serum levels of 25-hydroxyvitamin D and bone mineral density of femur neck of postmenopause women]. PMID- 8201941 TI - The structure-activity relationships of flavonoids as inhibitors of cytochrome P 450 enzymes in rat liver microsomes and the mutagenicity of 2-amino-3-methyl imidazo[4,5-f]quinoline. AB - The antimutagenicity of 19 naturally occurring flavonoids and their derivatives including flavones, flavonols, flavanones, isoflavones and flavanols were determined using Salmonella typhimurium TA98 against 2-amino-3-methylimidazo[4,5 f] quinoline (IQ) in the presence of Aroclor 1254-induced rat hepatic S9. In general, a relationship between the chemical structure of flavonoids and their antimutagenicity was found for compounds containing one or more of the following features: (i) C4 keto group, (ii) aglycone, (iii) double bond at positions C2 and C3, (iv) phenyl group at position C2, and (v) three hydroxy substituents at positions C4', C5 and C7. The inhibitory effects of flavonoids on activities of 7 ethoxycoumarin deethylase (ECD) and 7-ethoxyresorufin deethylase (ESD) of Aroclor 1254-induced hepatic microsomes were also examined. In addition, we studied the effects of flavonoids on the metabolism of IQ by Aroclor 1254-induced microsomes using high-performance liquid chromatography. The antimutagenicity correlated with the inhibition of cytochrome P-450IA1-linked ESD and P-450IA2-linked ECD activity in hepatic microsomes, and with an inhibition of N-hydroxy-IQ formation from IQ metabolism by hepatic microsomes. These results indicated that flavones or flavonols that contain C5, C7 and C4' hydroxyl groups are potent inhibitors of P-450 enzyme activities induced by Aroclor 1254 (P-450IA1 and P-450IA2), and may potentially be useful as chemopreventive agents against heterocyclic amine induced mutagenesis or carcinogenesis. PMID- 8201942 TI - Modulation of the mutagenic activity of cigarette smoke, cigarette smoke condensate and benzo[a]pyrene in vitro and in vivo. AB - A series of naturally occurring compounds were tested for the ability to modulate the mutagenicity induced by cigarette smoke (CS), cigarette smoke condensate (CSC) and benzo[a]pyrene (BP) in the Salmonella/microsome mutagenicity assay and the micronucleus test in mouse bone marrow. Sodium selenite, retinol acetate and alpha-tocopherol significantly decreased the mutagenic activity of CS in Salmonella typhimurium TA98. Ascorbic acid, reduced glutathione (GSH), cysteine, caffeine, theophylline, cobalt chloride, folic acid, adenine, adenosine, guanosine, cytidine and cytosine were conversely devoid of any significant effect. Sodium selenite slightly decreased the mutagenic activity of CSC in the same bacterial strain, while caffeine was ineffective and ascorbic acid potentiated its mutagenicity. Ascorbic acid inhibited the mutagenic activity of BP in S. typhimurium TA98, but not in TA100. Retinol acetate diminished the number of BP-induced his+ revertants in TA98 but only at the highest concentrations used, whereas alpha-tocopherol, GSH, cysteine, sodium selenite and caffeine had no effect. Selenite and GSH, which were ineffective when applied individually, inhibited in a dose-dependent manner the BP-induced mutagenesis in S. typhimurium TA98 when simultaneously added to the top agar. All other combinations tested, including selenite plus either GSH, cysteine or caffeine towards CS or CSC, or selenite plus cysteine, or selenite plus retinol acetate and alpha-tocopherol towards BP, failed to produce interactive effects. Sodium selenite and caffeine, given either alone or in combination in drinking water, did not influence the clastogenesis induced in mouse bone marrow by a single treatment with CS or BP. Ascorbic acid was also ineffective towards CS clastogenicity but significantly decreased the number of micronucleated polychromatic erythrocytes induced by BP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201943 TI - The molecular nature of mutations induced by adriamycin at the hprt locus of V79 cells. AB - Adriamycin (AM), a widely used chemotherapeutic drug, induced a broad spectrum of gene mutations at the hprt locus of V79 cells. The frequency and distribution of AM-induced deletions was analyzed with multiplex polymerase chain reaction in two V79 cell lines, which differed considerably in their spontaneous deletion frequency. Among AM-induced mutants, deletions predominated in both cell lines. Apart from total deletions of the hprt gene, partial deletions were found which were distributed all over the hprt gene with breakpoints in nearly all introns. Under the same experimental conditions, chromosome aberrations were induced by AM which mainly represented chromatid-type aberrations. Neither the induction of gene mutations nor the induction of chromosome aberrations was enhanced by the repair inhibitor 3-aminobenzamide. These results are discussed in the context with our earlier findings on bleomycin-induced mutations and it is suggested that at least two mechanisms lead to the formation of gene deletions. One of them seems to be associated with a misrepair process of frank DNA double-strand breaks and related to chromosome aberrations while the other is not. PMID- 8201944 TI - Video time-lapse study of mitosis in binucleate V79 cells: chromosome segregation and cleavage. AB - Binucleate V79 Chinese hamster cells were video time-lapse recorded during mitosis. The general pattern found was: formation of one integrated metaphase plate, most often in a tetra- or tripolar spindle, prolonged prometaphase/metaphase, and normal duration of anaphase and contraction of cleavage furrows. Cleavage, however, often showed partial regression. Reversal of cleavage usually occurred late and then was not clearly separable from fusion of daughter cells. Reversal/fusion was more common the more furrows were initiated in late anaphase. This suggests that a final part of cleavage, or establishment of daughter cell integrity, is hampered by the preceding complex chromosome/spindle arrangements in the binucleate cells. Lagging of chromosomes in anaphase and formation of micronuclei were found to be frequent events. The nuclei formed from cells with a tetra- or tripolar spindle were often uneven in size, suggesting that the cells have difficulties in distributing the chromosomes in an organized way between many poles. A comparison with previous studies of binucleate mitoses in other cell lines shows major similarities in the mitotic performance. It is suggested that induction of binucleate cells should be included as a relevant end point when screening novel compounds for toxicity and aneuploidy. PMID- 8201945 TI - Parametric analysis of rank transformed data for statistical assessment of genotoxicity data with examples from cultured mammalian cells. AB - The utility of rank transformation followed by parametric analysis of the ranks has been assessed for determination of the statistical significance of genotoxicity data. Both nonparametric and parametric analytical methods have defects when used to assess the significance of results from routine regulatory tests. Superficially, the rank transformation method followed by parametric analysis of ranks appears to be an ideal solution. However, we considered that such a test might suffer a substantial loss of power when used to analyse normally distributed data with very low sample replication. To test this hypothesis we took 22 data sets from five 'borderline' positive compounds in mouse lymphoma treat-and-plate assays where treatment-related increases were between 1.5- and 3-fold the control and analysed these results by Dunnett's t test using rank transformed data and weighted, untransformed data. In theory these mouse lymphoma data should show the rank transformation system at its worst in comparison with parametric methodology using weighted data. Surprisingly, the rank transformation methodology showed no loss of power and, overall, performed more consistently than the weighted data methodology. Based on this limited number of data sets, rank transformation followed by parametric analysis of ranks seems to be an approach very suitable for genotoxicity assays in general, particularly where distributions are non-normal or of uncertain form. It combines the general applicability of non-parametric methods with the power of parametric analyses. However, the methodology still requires to be further validated in use and by computer simulation. PMID- 8201946 TI - Effect of distamycin on chlorambucil-induced mutagenesis in pZ189: evidence of a role for minor groove alkylation at adenine N-3. AB - Previous work has shown that the bifunctional alkylating agent chlorambucil induces thermolabile adenine adducts and that the predominant chlorambucil induced mutations in shuttle vector pZ189 are transversions at AT base pairs. In order to assess the role of thermolabile adducts in generating these transversions, pZ189 was treated with chlorambucil in the presence of distamycin, which specifically blocks formation of thermolabile adenine adducts. Analysis of the mutations resulting from replication of the damaged vector in human 293 cells showed that base substitutions at AT base pairs were specifically suppressed in concert with suppression of thermolabile adducts at specific sites in the supF target gene, strongly supporting a role for these adducts in mutagenesis. Since there is considerable evidence that these adducts are N-3 alkylations, a computer graphics model of such an adduct was constructed. Modeling studies indicated that the adduct could be formed with little distortion of the DNA helix. Analysis of the adduct using the HINT (Hydropathic INTeractions) program was consistent with the proposal that favorable hydrophobic interactions of the phenyl ring of chlorambucil with the wall of the minor groove may promote adenine N-3 alkylation by this drug. PMID- 8201947 TI - Structural basis of the induction of unscheduled DNA synthesis in rat hepatocytes. AB - The structural basis of the induction of unscheduled DNA synthesis (UDS) in isolated rat hepatocytes was studied with CASE, an expert system. The analysis identified a number of structural determinants associated with the induction of UDS. These structures accounted for 97.3% of the activity of the chemicals in the database. Further analyses indicated that the concordance between prediction and experimentally determined UDS of molecules not in the learning set is > 82%. A comparison of predictions of UDS and mutagenicity in Salmonella indicated that there is a dichotomy between these activities. The basis of this lack of coincidence remains to be elucidated. PMID- 8201948 TI - Chromosome painting analysis of X-ray-induced aberrations in human lymphocytes in vitro. AB - Chromosomal rearrangements in human lymphocytes induced by X-rays (0, 0.5, 1.0 and 2.0 Gray) were analyzed using chromosome painting. DNA probes for human chromosomes 1, 3 or 4 alone, and a combination of 1 and 4, were used for analysis. The frequency of cells with rearrangements, i.e. reciprocal translocations, dicentrics, insertions, tricentrics and fragments, involving chromosome 4 increased with dose in both 48 and 72 h cultures. The number of translocations per cell also increased with dose at 48 and 72 h. Dicentrics increased with dose in 48 h but not in 72 h cultures. The estimated genomic frequency of aberrations per cell was comparable with results in banded cells. No difference was shown on the detection efficiency of chromosome rearrangements among the various DNA probes used. Since this technique does not necessarily require well-spread metaphases for analysis, it is possible to increase the number of analyzable metaphases compared with the banding technique. Chromosome painting is a simpler, more objective and more practical method for detecting chromosome rearrangements than conventional banding analyses. PMID- 8201949 TI - Characterization of the mutagen 2-amino-3-methylimidazo[4,5-f]quinoline prepared from a 2-methylpyridine/creatinine/acetylformaldehyde model system. AB - A mixture of 2-methylpyridine, creatinine and aldehydes was heated in diethylene glycol containing 5% water for 1 h at 140 degrees C. The mutagenic compounds were purified by XAD-2 column chromatography, acid/base partition, blue cotton treatment, thin layer chromatography and HPLC. The active substances purified from each step were monitored by their mutagenicity with Salmonella typhimurium TA98 in the presence of S9 mix. Among the mutagens collected, 2-amino-3 methylimidazo[4,5-f]quinoline (IQ) was isolated from HPLC, and was identified by its UV and mass spectrum using a photodiode array detector and mass spectrometry. Our findings appear to be the first experimental evidence to substantiate the hypothetical pathway for the formation of IQ mutagens from a heated model system consisting of a pyridine or pyrazine derivative, an aldehyde and creatinine or creatine. PMID- 8201950 TI - Gene mutation and V(D)J recombination in the radiosensitive irs lines. AB - The lines irs1, irs2 and irs3, derived from V79-4 hamster cells, are sensitive to DNA-damaging agents including ionizing radiations. However, unlike some other radiosensitive lines, the irs lines show no apparent defect in the repair of DNA strand breaks. We have now assessed the mis-repair of DNA damage in the irs lines by measuring spontaneous and X-ray induced frequencies of mutation in the HPRT gene. irs1 was found to be hypermutable, showing instability in spontaneous mutant frequency and an elevation of the radiation-induced frequency relative to the parental line. In contrast, irs2 and irs3 showed similar mutational responses to the parental line. The results support other lines of evidence suggesting that irs1 has a mis-repair phenotype. The irs2 line has previously been shown to have a phenotype similar to cells from the human disorder ataxia-telangiectasia and this similarity is maintained in their mutational response to X-rays. The irs lines were also tested for ability to undergo V(D)J recombination, since this process has recently been found to be defective in some radiosensitive lines with impaired double-strand break repair. Using an extrachromosomal vector containing a V(D)J rearrangement cassette, correct recombination was shown to occur at similar frequencies to parental V79-4 cells in each of the three irs lines. Thus the irs lines indicate that processes other than DNA double-strand break repair also control radiosensitivity, in particular those processes which may affect the regulation of DNA repair. PMID- 8201951 TI - K-region oxides and imines derived from alkylated benz[a]anthracene congeners: synthesis, stability in aqueous media and mutagenicity. AB - The K-region oxides and imines of benz[a]anthracene, 1-methylbenz[a]anthracene, 7 methylbenz[a]anthracene, 7-ethylbenz[a]anthracene and 7,12 dimethylbenz[a]anthracene were synthesized and characterized (melting point, 1H NMR and electron impact mass spectra, elemental analysis, IR spectroscopy). All 10 compounds showed high mutagenic activity in Salmonella typhimurium (reversion of his- strains TA97, TA98, TA100 and TA104). The arene imines were more potent than the corresponding arene oxides. Alkyl substitutions strongly influenced the activities. Furthermore, all compounds were more active when exposure took place in the absence of inorganic ions than when KCl (125 mM) was present. The influence of the exposure medium was more pronounced with strain TA98 than with strain TA100. The half-lives of the test compounds were determined from mutagenicity experiments in which the compound was added to the exposure medium at varying times before the bacteria. In dilute sodium phosphate buffer (10 mM, pH 7.4), the half-lives of these chemicals (or their biological activity) varied from 0.5 to 110 min. Addition of KCl (150 mM) did not measurably affect the half lives of some test compounds and appeared to slightly shorten those of others. Therefore, it is unlikely that the strong effect of KCl on mutagenicity and the dependence of this effect on the bacterial strain used can be explained by influences of KCl on the test compounds. Rather, it appears more likely than an effect of KCl on the bacteria may be an important factor. This study provides further examples of strong influences of unobtrusive media components on mutagenicity. It also demonstrates that small structural changes (alkyl substituents at diverse positions of the aromatic system) may play an important role in chemical reactivity and biological activity. PMID- 8201952 TI - Genotoxicity of paracetamol in mice and rats. AB - The genotoxicity of paracetamol, including covalent binding to DNA, induction of DNA single-strand breaks (SSBs), and inhibition of replicative and repair synthesis of DNA, has been investigated in rodents in vivo. In the covalent binding studies male ICR mice were fasted and pretreated with diethyl maleate to deplete hepatic glutathione (GSH) and 300 mg/kg of [G-3H]paracetamol was administered intraperitoneally (i.p.). Animals were killed at 2, 6, 24, 72 and 168 h after paracetamol and hepatic or renal DNA and protein were isolated and the extent of covalent binding determined. Maximal binding to liver DNA, 8.4 +/- 3.1 pmol/mg of DNA, was observed at 2 h and declined rapidly to 2.6 pmol/mg at 24 h. Measurable binding (1.4 pmol/mg of DNA) was detected at 7 days. Protein binding in the liver in these animals peaked between 2 and 6 h (887 pmol/mg of protein at 2 h) and declined monoexponentially to 52 pmol/mg at 7 days. Although based on a limited body of data, covalent binding was also detected in DNA isolated from the kidney. DNA damage measured as SSBs by alkaline elution was induced in nuclear DNA isolated from the liver but not from the kidney, 2 h after i.p. injection of paracetamol at 600 mg/kg in male B6 mice. Only marginal DNA damage was noted at 300 mg/kg. The alkaline elution profile from damaged liver nuclei was markedly biphasic, suggesting that breaks were induced in DNA from a subpopulation of liver cells. The non-hepatotoxic paracetamol regioisomer, acetyl m-aminophenol (600 mg/kg), which binds covalently to proteins, did not cause DNA SSBs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201953 TI - Alterations in reverse cholesterol transport associated with programmable implantable intraperitoneal insulin delivery. AB - Our previous studies have suggested that intraperitoneal (IP) insulin delivery may be associated with alterations of reverse cholesterol transport (RCT). We thus studied two parameters of RCT. We performed RCT studies in 10 C-peptide negative type I diabetic patients who were randomized into two groups. The experimental (A) and control (B) groups were studied at -3 and 0 months before and +3 and +6 months after IP pump subcutaneous (SC) insulin use. The first step in RCT was estimated by measuring patient serum-mediated 3H-cholesterol efflux from cultured fibroblasts. Cholesteryl ester transport protein (CETP) activity was assessed by a solid-phase assay. No changes in glucose control occurred during the study. Total low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, apoprotein B, and apoprotein A-I remained unchanged during the study. Cholesterol efflux from group A increased from baseline after 3 months of IP insulin by 9.5% +/- 3.4% (mean +/- SE, P < .05), whereas in group B patients it decreased negligibly by 1.5% +/- 2.9% (P = .045 for changes between groups). CETP activity increased from baseline by 25.3% +/- 7.7% (P < .05) in group A after 3 months of IP insulin, whereas in group B it changed little, -1.5% +/- 7.9%, with modest differences between groups (P = .16). These data indicate that (1) serum from patients treated long-term with IP insulin delivery may enhance cholesterol efflux from fibroblasts and CETP activity, and (2) these effects appear independent from glucose control, implying a direct effect by IP insulin. PMID- 8201955 TI - Changes in plasma dolichol levels, transport, and hepatic delivery during rat liver regeneration. AB - During the proliferative process that follows partial hepatectomy in the rat, the dolichol content increases in both plasma and liver. Its transport in the blood by lipoproteins also changes. The difference in the distribution of dolichols of various chain lengths in plasma and in the liver is further enhanced during liver regeneration. The dolichol released by perfused liver shows a homologue distribution more similar to that observable in blood than in the liver, thus confirming the importance of the liver as a regulatory site for the blood dolichol supply. PMID- 8201954 TI - Effect of hepatectomy on glucose metabolism in the dog. AB - The response of whole-body glucose uptake and oxidation and hindlimb glucose and lactate balance was investigated using the hyperinsulinemic, euglycemic clamp in 12 sham-operated control dogs and 10 hepatectomized dogs. A combination of radioactive (NaH14CO3) and stable (U-13C-glucose) isotope tracers was used to quantify glucose kinetics and oxidation. The insulin concentration was increased to approximately 5,000 microU/mL. Mean glucose uptake rates across the hindlimb were similar, 7.72 and 8.06 mumol.kg-1.min-1 for hepatectomy and sham-operated groups, respectively. Lactate release across the hindlimb also showed no significant differences between the two groups. Therefore, it was concluded that the liver did not affect peripheral glucose uptake in response to supramaximal insulin infusion under these experimental conditions. On the other hand, the mean glucose infusion rate during the last 60 minutes of the insulin clamp in the hepatectomy group was significantly decreased compared with that in the sham operated group, 57.11 versus 46.29 mumol.kg-1.min-1, respectively (P < .05). Consequently, the maximal capacity of the liver of the anesthetized dog to clear glucose in response to supramaximal insulin infusion appears to be approximately 10.8 mumol.kg-1.min-1, which is about 20% of the total glucose infused. Isotopic data showed that most hepatic glucose uptake was oxidized. In contrast, most peripheral glucose uptake appeared to be stored as glycogen. PMID- 8201956 TI - Liver regrowth and apolipoprotein B secretion by rat hepatocytes following partial hepatectomy. AB - Apolipoprotein (apo) B is an essential component for the assembly and secretion of lipoproteins. The current report examines apo B production using primary cultures of hepatocytes derived from rats 3 to 21 days after partial hepatectomy (PH) to determine the effects of liver regrowth on apo B. Studies indicate that hepatocytes stimulated by PH have a two-thirds reduction in net apo B production 3 to 7 days after surgery, which coincides with the period of maximum rate of liver regrowth. Both higher (apo BH)- and lower-molecular-weight (apo BL) apo B are synthesized and secreted after PH, indicating the presence of edited apo B mRNA in hepatocytes. Hepatocytes derived from PH rats are more sensitive to insulin inhibition of apo B secretion compared with controls, suggesting an enhanced effect of insulin on newly replicated hepatocytes. Epidermal growth factor (EGF), a key regulator of liver regrowth following PH, potentiates the inhibitory action of insulin on apo B secretion in control hepatocytes and those derived from rats 2 to 3 weeks after PH. However, the potentiating effect of EGF on insulin inhibition of apo B is not discernible in hepatocytes 3 to 7 days after PH. The short-term in vitro hormonal effects occurring even with decreased apo B production suggest that this pathway remains available following PH to balance lipoprotein secretion with lipid and energy requirements necessary for liver regeneration. PMID- 8201957 TI - Regulatory factors in the development of fatty infiltration of the liver during gram-negative sepsis. AB - To further understand the development of fatty liver during gram-negative sepsis, we measured fatty acid uptake in addition to esterification and secretion of lipids by freshly isolated hepatocytes from fasted and fed control and Escherichia coli-treated rats. Rats were made septic by intravenous (IV) injection of 8 x 10(7) live E coli colonies per 100 g body weight. For the fasted groups, food was removed after E coli injection. Fed rats received a nutritionally adequate diet intragastrically for 5 days before and 24 hours after inducing sepsis. Twenty-four hours after E coli injection, the esterification of newly synthesized fatty acids, as measured by 3H2O incorporation, and the esterification of exogenous fatty acids, measured from 14C-palmitate incorporation, into triglyceride (TG), total cholesterol, and total phospholipid phosphorus were significantly greater in hepatocytes from fasted septic rats compared with their control rats. In fed septic rats, esterification of 14C palmitate into TG was fourfold greater than in the fed control rats. The increased rates of esterification in hepatocytes from fasted and fed septic rats were not accompanied by an increase in the labeled TG in the medium. This inability to secrete the additional TG that the hepatocytes produce resulted in a higher concentration of cellular TG in fasted and fed septic rats than in their controls. The enzymes glycerol-3-phosphate acyltransferase (GPAT) and phosphatidate phosphohydrolase (PPH) do not appear to be factors contributing to the increased TG synthesis, since the increase in enzyme activity was not accompanied by a similar increase in TG synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201958 TI - Body fat distribution has weight-independent effects on clinical, hormonal, and metabolic features of women with polycystic ovary syndrome. AB - This study was performed to investigate whether different patterns of body fat distribution may have distinct effects on the clinical, hormonal, and metabolic features of women with clinical hyperandrogenism such as polycystic ovary syndrome (PCOS). Ninety-seven consecutive women with PCOS were included in the study after assessment of gynecological and obesity history and careful clinical examination. Women were divided into three tertile groups based on the waist to hip ratio (WHR). Those with peripheral body fat distribution (P-BFD) had a WHR of less than 0.80, those with intermediate body fat distribution (I-BFD) had a WHR of 0.81 to 0.90, and those with abdominal body fat distribution (A-BFD) had a WHR exceeding 0.90. Baseline blood and urine samples were obtained for several hormone and lipid determinations, and the response of glucose, insulin, and C peptide to a glucose oral challenge (75 g) was investigated. In the PCOS group, WHR values were higher than those used to define P-BFD and A-BFD in the normal female population. As WHR values increased, a significantly greater prevalence of obesity and acanthosis nigricans and a lower prevalence of acne was present. No significant differences were present in any of the other clinical features between the three groups. Ovarian morphology and volumes were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201959 TI - Insulin sensitivity, insulin secretion, and glucose effectiveness in subjects with impaired glucose tolerance: a minimal model analysis. AB - The aim of the present study was to estimate insulin secretion, insulin sensitivity (SI), and glucose effectiveness (SG) in non-obese Japanese subjects with impaired glucose tolerance (IGT). Ten IGT subjects (five men, five women) and 15 normal-tolerance subjects (seven men, eight women) without a family history of diabetes were studied. They underwent a modified frequently sampled intravenous glucose tolerance test (FSIGT); glucose (300 mg/kg body weight) was administered, and insulin (20 mU/kg over 5 minutes) was infused from 20 to 25 minutes after the administration of glucose. SI and SG were estimated by Bergman's minimal model method. No significant difference was observed in body mass index ([BMI] 22.1 +/- 0.8 v 21.1 +/- 0.5 kg/m2), fasting plasma glucose (5.19 +/- 0.18 v 5.07 +/- 0.11 mmol/L), and insulin levels (50.7 +/- 7.3 v 45.2 +/- 4.5 pmol/L) of subjects with IGT and normal controls. The glucose disappearance rate (KG) was significantly lower in subjects with IGT than in normal-tolerance subjects (1.57 +/- 0.20 v 2.09 +/- 0.15%/min, P < .05). Pancreatic insulin secretion expressed as the integrated area of plasma insulin above the basal level during the first 20 minutes was lower in IGT subjects (2,556 +/- 572 pmol/L x min) than in normal-tolerance subjects (4,957 +/- 800 pmol/L x min, P < .05). SI was not statistically different between the two groups (0.84 +/- 0.13 x 10(-4) v 1.14 +/- 0.15 x 10(-4).min-1.pmol/L-1). However, SG was significantly lower in subjects with IGT than in normal controls (0.013 +/- 0.002 v 0.023 +/- 0.002 min-1, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201960 TI - Increased neutrophil chemiluminescence production in patients with cystic fibrosis. AB - Increased free radical production has been suggested as a possible mechanism involved in lung deterioration of patients with cystic fibrosis (CF). Vitamins A and E are known to be involved in the defense mechanism preventing damage caused by free radicals. Both vitamins are fat-soluble and are therefore malabsorbed in patients with CF. We hypothesized that low concentrations of vitamins A and E may be involved in the increased free radical production of these patients. Neutrophils' chemiluminescence and superoxide and hydrogen peroxide production were examined in 11 patients with CF aged 4 to 14 years, and 10 age-matched healthy controls. All our patients were on prolonged supplementation with vitamins A and E, but the control group was not supplemented. Serum vitamins A and E levels and neutrophil vitamin E concentrations were examined concomitantly. Chemiluminescence production was increased 10 minutes after neutrophil stimulation by phorbol myristate acetate (PMA) as compared with that in normals (20,400 +/- 9,463 v 11,990 +/- 3,778 cpm, P < .03). No difference was found in superoxide or hydrogen peroxide production between CF patients and controls. Serum vitamin A levels were significantly higher in CF patients compared with healthy controls (0.641 +/- 0.049 v 0.398 +/- 0.038 mg/L, P < .04) and so were vitamin E levels (13.94 +/- 2.25 v 5.64 +/- 1.15 mg/L, P < .05). Neutrophil vitamin E concentrations were higher in CF patients compared with healthy controls (70.8 +/- 26.0 v 23.6 +/- 9.0 micrograms/10(6) cells). We conclude that neutrophils from CF patients exhibit increased chemiluminescence activity not related to increased free radical production or fat-soluble vitamin deficiency. PMID- 8201961 TI - Adrenal effects of low-dose aminoglutethimide when used alone in postmenopausal women with advanced breast cancer. AB - Aminoglutethimide (Ag) is a potent aromatase-enzyme inhibitor used in the treatment of patients with breast cancer. In the past, it has been administered in doses of 1,000 mg/d (usually with 40 mg hydrocortisone). At these dose levels, the drug also affects multiple cytochrome P-450 enzymes, including enzymes for adrenal steroid biosynthesis. Recently, lower-dose regimens (500 mg/d) of Ag have been found to be just as effective for breast cancer therapy, but less toxic than the higher conventional dose. There is limited information on the adrenal effects at the lower dosages, and it is not known whether these effects are clinically significant. We measured basal and synthetic corticotropin (Cortrosyn)-stimulated levels of adrenal steroids in postmenopausal breast cancer patients before and during treatment with low-dose Ag (500 mg/d) administered without a glucocorticoid preparation. Basal levels of progesterone, 17-OH progesterone, and 11-deoxycortisol were higher after 2 months' treatment (P < .01). After ACTH injection, peak levels of progesterone and 17-OH progesterone were higher (P < .01), but in contrast, peak levels of 18-OH corticosterone were lower during treatment (P < .02). Basal and peak levels of cortisol, aldosterone, and all other adrenal steroids were unchanged during treatment. We conclude that low-dose Ag treatment leads to partial inhibition of the 21-hydroxylase, 11-hydroxylase, and 18-hydroxylase adrenal enzymes. Since cortisol and aldosterone secretion remained normal with minimal shunting to or accumulation of adrenal androgen compounds, we believe that the mild inhibition was compensated for by further endogenous ACTH stimulation. PMID- 8201962 TI - Effect of propionate on in vivo carbohydrate metabolism in streptozocin-induced diabetic rats. AB - Undigested carbohydrates and some dietary fibers are fermented in the large intestine to form short-chain fatty acids (SCFA), including acetate, propionate, and butyrate. It has been suggested that some of the beneficial effects of high carbohydrate, high-fiber diets on carbohydrate and lipid metabolism are mediated by the metabolism of SCFA in the liver. Propionate has been shown in vitro to decrease glucose production in rat hepatocytes. The aim of the present study was to investigate the effects of propionate on carbohydrate metabolism in normal and streptozocin (STZ)-induced diabetic male Sprague-Dawley rats. Rats were fed a high-fat diet with or without sodium propionate supplementation (either 0.5% or 5% wt/wt) for 4 weeks. At the completion of the feeding period, body weight and liver glycogen concentrations were significantly decreased in STZ-diabetic rats and were unaffected by propionate supplementation. Although STZ-diabetic animals had elevated fasting plasma glucose, cholesterol, and triglyceride levels relative to nondiabetic rats, propionate supplementation had no significant effect on these parameters in either group. Basal and insulin-stimulated carbohydrate metabolism were assessed using the euglycemic clamp technique in overnight-fasted animals with 3(H)-6-glucose infusion. As expected, basal hepatic glucose production (HGP) was higher and the metabolic clearance rate of glucose (MCR) was lower in STZ-diabetic rats. High-dose insulin infusion (3 mU.kg-1.min 1) suppressed HGP in nondiabetic and diabetic animals and increased the MCR in nondiabetic animals. However, propionate supplementation did not alter basal or insulin-stimulated HGP or the MCR in either nondiabetic or diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201963 TI - L-phenylalanine releases cholecystokinin (CCK) and is associated with reduced food intake in humans: evidence for a physiological role of CCK in control of eating. AB - Exogenous administration of cholecystokinin (CCK) reduces food intake in humans; however, it is not clear if endogenous CCK is a true satiety hormone. The aim of this experiment was to manipulate endogenous release of CCK using L-phenylalanine (L-PA), a potent releaser of CCK, and to measure subsequent food intake. On separate occasions, six normal-weight fasted subjects (four men, two women) were administered 10 g of L-PA, D-PA, or placebo 20 minutes before being presented with a standard meal of known calorie content. Preliminary experiments had shown that peak plasma concentrations of CCK were obtained 20 minutes after administering L-PA. The test meal was given to coincide with this peak. One hundred-millimeter visual analog scales (VAS) to assess hunger, desire to eat, and fullness were completed premeal, postmeal, and at intervals thereafter. Blood was taken before administering PA/placebo immediately premeal and postmeal and stored for measurement of CCK levels by bioassay. Subjects consumed 1,089 +/- 86 kcal after L-PA (P = .03) compared with 1,587 +/- 174 kcal after placebo and 1,492 +/- 126 kcal after D-PA. The reduction in calorie intake after L-PA was associated with a significantly greater sensation of fullness. Basal levels of CCK were 1.10 +/- 0.12 pmol/L; 20 minutes after L-PA, CCK levels increased to 5.49 +/- 0.83 pmol/L. There was no increase in CCK following D-PA or placebo. Release of CCK by L-PA is associated with a reduction in subsequent food intake, and this suggests that CCK is an important satiety hormone in humans. PMID- 8201964 TI - Pituitary adenylate cyclase-activating polypeptide: effects on pancreatic-adrenal hormone secretion and glucose-lipid metabolism in normal conscious dogs. AB - The effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on plasma insulin, glucagon, catecholamine, cortisol, glucose, triglyceride (TG), free fatty acid (FFA), cholesterol, and cyclic adenosine monophosphate (cAMP) concentrations were examined in unanesthetized normal dogs. A bolus injection of 6 pmol/kg PACAP27 elicited a transient increase in plasma insulin, epinephrine, and norepinephrine concentrations, with a peak value at 2 minutes after injection. Injections of 60 and 600 pmol/kg caused greater increases in these hormone concentrations in a dose-dependent manner. The plasma cortisol concentration was not changed by a bolus injection of 6 pmol/kg PACAP27, and was gradually increased by injections of 60 and 600 pmol/kg. Significant increases were observed from 10 and 5 minutes after the injection of 60 and 600 pmol/kg, respectively. The plasma glucagon concentration was not changed by either 6, 60, or 600 pmol/kg. The plasma glucose concentration decreased with 60 pmol/kg PACAP27 and increased with 600 pmol/kg. The plasma FFA concentration was increased gradually, with a peak value at 10 minutes after the injection, in a dose-dependent manner. The plasma TG concentration was slightly increased with 600 pmol/kg with a peak value at 10 minutes, although plasma cholesterol did not change. The plasma cAMP concentration increased significantly with 600 pmol/kg PACAP27, but not with 6 or 60 pmol/kg. These effects of PACAP27 were observed with a bolus injection of PACAP38 of an equal potency. Infusion of graded doses of PACAP27 (1, 3, and 10 pmol/kg/min every 20 minutes) caused a gradual increase in plasma cortisol, catecholamine, FFA, and cAMP concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201965 TI - Influence of daily drinking habits on ethanol-induced hyperuricemia. AB - We examined the influence of alcohol drinking habits on the serum uric acid level after the ingestion of a small amount of ethanol. Subjects were divided into two groups according to their alcohol drinking habits--regular drinkers, who consume more than 60 g ethanol every day, and nondrinkers/occasional drinkers, who consume less than 20 g ethanol occasionally. Drinking 0.5 g ethanol/kg increased serum uric acid levels in regular drinkers by 52.6 +/- 26.3 mumol/L (0.8 +/- 0.4 mg/dL), whereas it did not in nondrinkers/occasional drinkers. Urinary excretion of uric acid was unaltered in both groups. Hypoxanthine and xanthine in both plasma and urine and serum acetate were increased more in regular drinkers than in nondrinkers/occasional drinkers. Accelerated adenine nucleotide degradation secondary to enhanced ethanol oxidation likely explains the ethanol-induced hyperuricemia in regular drinkers. PMID- 8201966 TI - Disorders of carbohydrate and lipid metabolism in veterans with paraplegia or quadriplegia: a model of premature aging. AB - One hundred veterans with paralysis due to spinal cord injury (SCI), equally divided between those with paraplegia and quadriplegia, and 50 able-bodied veteran controls underwent a 75-g oral glucose tolerance test (OGTT). In subjects with SCI, 22% were diabetic by criteria established by the World Health Organization (WHO), whereas only 6% of the control group were diabetic. Eighty two percent of the controls had normal (NL) oral glucose tolerance, compared with 38% of those with quadriplegia and 50% of those with paraplegia. Subjects with diabetes mellitus (DM) were older in both the SCI and control groups, but those with SCI developed carbohydrate disorders at younger ages than did the control group. SCI subjects had significantly higher mean glucose and insulin values at several points during the OGTT when compared with controls, suggesting an accentuated state of insulin resistance in those with SCI. Mean fasting plasma glucose (FPG) values for both SCI and control groups were significantly higher in subjects with DM compared with those with NL glucose tolerance. When the FPG value was compared between SCI or control subjects with abnormalities in glucose tolerance, the subgroups with SCI and NL or impaired glucose tolerance (IGT) had significantly lower FPG levels than the respective control subgroups, suggestive of decreased hepatic glucose output in SCI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201967 TI - Insulin receptor mutation at tyrosines 1162 and 1163 alters both receptor serine phosphorylation and desensitization. AB - Chinese hamster ovary (CHO) cells expressing human insulin receptor (hIR) of the wild-type (CHO R) or hIR mutated at tyrosines 1162 and 1163 (CHO Y2) were compared for agonist-induced receptor phosphorylation of serine/threonine residues and receptor desensitization. Relative to CHO R cells, CHO Y2 cells exhibited a marked decrease in their response to insulin and 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) for hIR phosphorylation on serine residues. Moreover, the tyr1162,1163 mutant hIR could not be normally phosphorylated by purified protein kinase C (PKC) in vitro. Finally, in contrast to CHO R cells, CHO Y2 cells were refractory to PMA-induced IR desensitization for subsequent activation by insulin of exogenous tyrosine kinase and glycogen synthesis. These results strongly suggest that the replacement of tyrosines 1162 and 1163 by phenylalanine residues changes the IR beta-subunit conformation and thus impedes phosphorylation of the IR at crucial serine residues and prevents PMA-induced desensitization. This supports the hypothesis that IR serine phosphorylation and desensitization are related. PMID- 8201968 TI - Insulin treatment improves relative hypersecretion of amylin to insulin in rats with non-insulin-dependent diabetes mellitus induced by neonatal streptozocin injection. AB - The dissociated release of insulin and amylin in the hyperglycemic state has been reported. This relative hypersecretion of amylin is thought to provide an important insight into how amylin aggregates to form islet amyloid deposits in non-insulin-dependent diabetes mellitus (NIDDM). The aim of the present study was to characterize the alterations of amylin hypersecretion in NIDDM with exacerbation or amelioration of diabetic control. For this purpose, neonatally streptozocin (nSTZ) diabetic rats were treated with dexamethasone (0.25 mg/kg) or Lente insulin (3 to 5 U/kg) daily for 14 days, and responses of amylin and insulin to 16.7 mmol/L glucose or 10 mmol/L arginine were evaluated in vitro using an isolated perfused pancreas system. nSTZ rats exhibited moderate elevations of plasma glucose compared with normal rats. In the isolated perfused pancreas, the molar ratio of secreted amylin to insulin in response to 16.7 mmol/L glucose by nSTZ pancreas (1.8% +/- 0.2%) was significantly greater than that of normal rat pancreas (1.2% +/- 0.1%). Plasma glucose levels in nSTZ rats (7.3 +/- 0.4 mmol/L) increased with dexamethasone treatment (17.8 +/- 1.1 mmol/L, P < .005) and decreased with insulin treatment (5.8 +/- 0.4 mmol/L, P < .05). The secreted amylin to insulin ratio in dexamethasone-treated nSTZ rats was significantly greater than that of the controls (P < .05). Moreover, insulin treated nSTZ rats exhibited decreased amylin to insulin molar ratios compared with saline-treated nSTZ rats (P < .05), which had the same levels as normal rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201969 TI - Effect of C-terminal fragments of glucagon on insulin secretion in dogs. AB - Although the insulinotropic action of glucagon is well known, which parts of the glucagon molecule play an important role in its action remain to be elucidated. To investigate the direct effect of the C-terminal peptides of glucagon on the endocrine function of the pancreas, glucagon (17-29), (21-29), (23-29), and (25 29) were studied using an in situ local circulation system of the canine pancreas. These glucagon fragments, as well as glucagon(1-29), were infused into the superior pancreaticoduodenal artery (PA) in a dosage of 400 pmol for 10 minutes during 0.5% glucose or 0.5% arginine infusion, and plasma insulin (IRI) and glucagon (IRG) levels in the superior pancreaticoduodenal vein (PV) were determined. During the glucose infusion, plasma IRI increased significantly following the administration of glucagon(23-29), (21-29), (17-29), or (1-29), but not glucagon(25-29). In these experiments, plasma IRG increased significantly following infusion of glucagon(21-29), (17-29), or (1-29). During the arginine infusion, all of the glucagon fragments studied enhanced insulin secretion, whereas plasma IRG was increased following the administration of glucagon(21-29), or (1-29). In these experiments with glucose or arginine infusion, blood glucose in the femoral artery (FA) did not change significantly except for glucagon(1 29), which increased the blood glucose level. In addition, the administration of graded doses of glucagon(21-29) [50, 150, and 400 pmol] during the glucose infusion elicited an increase in plasma IRI in a dose-related manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201970 TI - Theophylline enhances glucose recovery after hypoglycemia in healthy man and in type I diabetic patients. AB - The principal mediators of glucose counterregulation (glucagon and epinephrine) use intracellular cyclic adenosine monophosphate (cAMP) to mediate glucose release. Since theophylline increases cAMP (by inhibiting its decomposition), we investigated the effect of theophylline on glucose recovery after insulin-induced hypoglycemia. Eleven healthy subjects and nine type I (insulin-dependent) diabetic patients each participated in two experiments in randomized order, receiving on both days an insulin bolus of 0.15 IU/kg soluble insulin. On one day, theophylline (intravenous [IV] bolus of 220 mg followed by IV infusion of 1 mg/kg/h) was administered from 1 hour before induction of hypoglycemia until the end of the study period. On the other day, NaCl was administered. Plasma glucose before induction of hypoglycemia was equal on the 2 study days. The plasma glucose area under the curve (AUC) was larger with theophylline than with NaCl (P = .04 for diabetic patients and P = .003 for healthy subjects). During the most active phase of glucose counterregulation, the rate of increase of plasma glucose was larger with theophylline (P = .003 for diabetic patients and P = .03 for healthy subjects). The incremental AUC for cAMP was larger with theophylline for diabetic patients (P = .01). For healthy subjects, cAMP was greater with theophylline 30 minutes after insulin (P = .03). In conclusion, glucose recovery after hypoglycemia is significantly increased when theophylline is administered in an asthma dosage before hypoglycemia is induced. This may be due to a significant enhancement of the cAMP response. PMID- 8201971 TI - Pulsatile thyrotropin secretion in patients with Cushing's syndrome. AB - Pulsatile and circadian thyrotropin (TSH) secretion were studied in 16 healthy controls and in three patients with Cushing's syndrome who were studied twice (before and after treatment). Blood was sampled every 10 minutes over 24 hours for TSH (immunoradiometric assay [IRMA]). Mean 24-hour TSH in Cushing's syndrome was lower than in controls (0.4 +/- 0.2 v 1.7 +/- 0.7 mU/L, P < .001), related to a lower mean 24-hour TSH pulse amplitude (Desade: 0.16 +/- 0.15 v 0.44 +/- 0.20 mU/L, P < .001; Cluster: 0.17 +/- 0.14 v 0.39 +/- 0.20 mU/L, P < .001; mean +/- SD). TSH pulse frequency was unchanged with approximately 10 pulses/24 h. The nocturnal TSH surge was diminished relative to controls (median-0, range- -0.03 to 0.2 mU/L v 0.9 and 0.3 to 2.5 mU/L, respectively), related to a loss of the usual nocturnal increase in TSH pulse amplitude, but not of TSH pulse frequency. In the eucorticoid state, there was an increase of mean 24-hour TSH to 1.3 +/- 0.8 mU/L (P < .001) under normalization of the mean 24-hour TSH pulse amplitude. The nocturnal TSH surge also increased (median, 0.21; range, 0.15 to 0.4 mU/L) under restoration of the usual nocturnal increase in TSH pulse amplitude. In conclusion, Cushing's syndrome is associated with a decrease of mean 24-hour plasma TSH, related to a decrease of TSH pulse amplitude (not of TSH pulse frequency). The nocturnal TSH surge is decreased in Cushing's syndrome associated with a loss of the usual nocturnal increase of TSH pulse amplitude.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201972 TI - Sex-related differences in iodothyronine metabolism in the rat: evidence for differential regulation among various tissues. AB - Various aspects of thyroid hormone metabolism were examined in vitro in age matched (experiment I) and weight-matched (experiment II) male and female Sprague Dawley rats; unless specified otherwise, results were similar in both experiments. The activity and content of iodothyronine 5'-monodeiodinase (type I MD) in the liver of the female rat were markedly reduced, but there was no sex related difference in these parameters in the kidney. The activity of the brain type III-MD was also not significantly influenced by the sex of the rat. Hepatic triiodothyronine (T3) sulfation activity in the females was only about 20% of that of the males. However, kidney and brain did not show this decrease in T3 sulfation. Similarly, hepatic T3 sulfate (T3S) desulfation activity was significantly reduced in the liver of the female rat (P < .001), whereas the activity in the kidney was either similar to (experiment I) or higher than (experiment II) that in the male, and the activity in the brain was similar in the two sexes. The mean serum T3S concentration in the female rat was no greater than 25% of the corresponding value measured in the male rat. The mean serum thyroxine (T4) concentration in female rats was similar to that in age-matched males (experiment I), whereas it was somewhat lower than that in weight-matched males (P < .05, experiment II). No significant difference in the mean serum T3 concentration was observed in rats of female and male sex. However, the mean serum thyrotropin (TSH) concentration in the female rat was significantly lower than that in the male.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8201973 TI - The vibrating Ca2+ electrode: a new technique for detecting plasma membrane regions of Ca2+ influx and efflux. PMID- 8201975 TI - Practical aspects of measuring [Ca2+] with fluorescent indicators. PMID- 8201974 TI - Application of patch clamp methods to the study of calcium currents and calcium channels. PMID- 8201976 TI - Rapid simultaneous estimation of intracellular calcium and pH. PMID- 8201977 TI - Improved spatial resolution in ratio images using computational confocal techniques. PMID- 8201978 TI - Confocal imaging of Ca2+ in cells. PMID- 8201979 TI - Simultaneous near ultraviolet and visible excitation confocal microscopy of calcium transients in Xenopus oocytes. PMID- 8201980 TI - Inexpensive techniques for measuring [Ca2+]i changes using a photomultiplier tube. AB - Photomultiplier tubes remain among the most sensitive methods for detecting light. Their cost is one to two orders of magnitude less than that of other comparably sensitive detectors. Advances in the associated electronics have lowered the cost and reduced the size of the instruments. If an investigator is willing to go to the primary suppliers and has access to a machine shop, systems sensitive enough for fluorescence measurements on single cells (or portions of a single cell) can be assembled for remarkably little money. In this chapter, we have emphasized a design using particular suppliers because we have used this system in our laboratory. The reader should not assume that we have explored all possibilities; further, progress in these areas tends to be rapid and new developments may open up additional opportunities. PMID- 8201981 TI - A practical guide to the preparation of Ca2+ buffers. PMID- 8201982 TI - Imaging [Ca2+]i with aequorin using a photon imaging detector. PMID- 8201983 TI - Photorelease techniques for raising or lowering intracellular Ca2+. PMID- 8201984 TI - Targeting recombinant aequorin to specific intracellular organelles. PMID- 8201985 TI - Pharmacological tools for perturbing intracellular calcium storage. PMID- 8201987 TI - To thrive under managed care, be prepared to negotiate. PMID- 8201986 TI - How to make and use calcium-specific mini- and microelectrodes. PMID- 8201988 TI - Genesee County's HIV programs serve as a model for community cooperation. PMID- 8201990 TI - Preparing for change. POs and PHOs are your ticket to autonomy and control. PMID- 8201989 TI - Preparing for change. MSMS offers the assistance you need. PMID- 8201991 TI - Preparing for change. MSMS joins forces with international consulting firm to assist physicians in preparing for health system reform. PMID- 8201992 TI - Preventing HIV infection, particularly in women and infants, an urgent public health priority, MDPH reports. PMID- 8201993 TI - Michigan Health Care Education and Research Foundation: sharing a vision of the future with Michigan physicians. AB - The aim of the Michigan Health Care Education and Research Foundation (MHCERF) is to support the development and analysis of ideas so that the citizens of Michigan may benefit ... MHCERF is proud of its efforts to support health and medical care research, as well as service in our state. In striving to improve medical care and health policy in Michigan, the aims, objectives and activities of the Michigan Health Care Education and Research Foundation (MHCERF) effectively complement the goals of Michigan physicians. MHCERF attempts to improve health and medical care primarily through the support of research. Moreover, MHCERF's success is in large part attributed to the physicians of Michigan. Receiving grants through MHCERF, physicians have conducted a substantial amount of high quality research for the Foundation. Since 1985, physicians and medical students in the state of Michigan have received 61 grants from MHCERF totaling approximately $1.8 million dollars, nearly half of all funded grants. The purpose of this article is two fold: (1) to communicate the purpose and mission of MHCERF to an important audience-Michigan physicians, and (2) to demonstrate the contribution Michigan physicians have made to the goals of MHCERF through the grants they've received, research they've conducted, and consultation they've provided. PMID- 8201994 TI - The wrong message of legalizing illicit drugs. PMID- 8201995 TI - Clinton's Health Security Act: promote and criticize. PMID- 8201996 TI - Michigan Court of Appeals upholds constitutionality of 1986 malpractice legislation. PMID- 8201997 TI - Monitoring heterosexual transmission of HIV through testing of antenatal women. PMID- 8201998 TI - Oesophageal cancer--guarded optimism. PMID- 8201999 TI - Psychiatric disorders among elderly patients in a general hospital. AB - OBJECTIVES: To determine the approximate point prevalence of psychiatric disorders among elderly patients in a general hospital and to ascertain the frequency of mental state examination on admission, psychotropic drug use and documentation of psychiatric disorder in discharge summaries. METHOD: Weekly enrollment of 10 beds until the entire hospital was screened. Patients aged over 65 years were interviewed with the Geriatric Mental State schedule and psychiatric diagnoses were made using the AGECAT computer program. PATIENTS AND SETTING: Inpatients aged 65 years and over in all wards of a metropolitan teaching hospital over 16 months in 1990-1991. RESULTS: Of 495 enrolled patients, 204 were aged over 65 years and 167 of these could be interviewed. Eighteen per cent showed evidence of organic mental impairment, 27% were depressed and 2% had other psychiatric disorders. Some mental state findings were recorded on admission for 25% of patients, 52% of patients were prescribed hypnotic or psychotropic drugs and 30% of the psychiatric disorders identified by the survey were mentioned in the discharge summary. CONCLUSIONS: Screening for psychiatric disorders in this setting is not routine. The frequency of such disorders makes it desirable to conduct prospective evaluation of the use of brief cognitive and depression screening instruments on admission to hospital. PMID- 8202000 TI - Major trauma outcomes in the elderly. AB - OBJECTIVES: To study mortality and functional outcome in elderly patients suffering major trauma and to assess whether age affects prognosis. DESIGN AND SETTING: Retrospective identification of patients from the Royal North Shore Hospital, a level three trauma service and teaching hospital of the University of Sydney. The patients were followed up for an average of three years after admission. PATIENTS: One hundred and eighteen patients aged over 60 years, with injury severity scores over 15, admitted consecutively between May 1988 and July 1990. To determine the effects of age on outcome, patients were divided into two groups: those aged 61-70 years (67 patients) and over 70 years (51 patients). MAIN OUTCOME MEASURES: Death in hospital, late death after discharge, change in preinjury v. current accommodation and current functional ability, measured with the Barthel activities of daily living index. RESULTS: Thirty-six of the 118 patients died in hospital. Eighty-one of the remaining 82 patients were followed up. Twenty-five of these patients died during the study period: three in the 61 70 years age group, and 22 in the over 70 years age group (P < 0.0001). Among the long term survivors, 43 of 53 continued to live independently, and 41 of 54 scored maximum points in activities of daily living assessment. Only seven people required nursing home care. CONCLUSIONS: Age is an important factor in survival after major trauma, but those that do survive generally return to full activity and independence. Aggressive treatment for elderly trauma victims is warranted. PMID- 8202001 TI - Free flaps in the aged and infirm. AB - Some of the most dramatic advances in reconstructive surgery have involved microvascular free-flap transfers. Although initial studies stressed the need for the procedures to be restricted to the healthy, with no evidence of vascular disease, it has become apparent that such restrictions need not apply if adequate patient care is available. Refinements of technique and development of new operations have made the free flap available to all. In particular, the procedure has been found to have unique benefits in the elderly and infirm population. PMID- 8202002 TI - Postural stability, falls and fractures in the elderly: results from the Dubbo Osteoporosis Epidemiology Study. AB - OBJECTIVE: To assess measures of postural stability in a large population of persons aged over 60 years in order to compare performance between fallers and non-fallers and relate postural stability to fracture prevalence. METHODS: The sensorimotor, visual and balance functions were measured in 1762 ambulatory, community-dwelling patients aged between 60 and 100 years (mean age, 70.1 years) living in a large semi-urban Australian city. A history of recent falls and fractures was recorded at the time of assessment. RESULTS: The prevalence of impairment in all tests increased with age. Men performed significantly better than women in tests of muscle strength, visual field dependence, sway on the floor with eyes open and dynamic balance. In the 12 months before testing, 72.3% of the patients experienced no falls, 18.4% fell only once and 9.3% fell on two or more occasions. Multiple fallers had weaker quadriceps, poorer tactile sensitivity, greater visual field dependence and greater body sway than other patients. Test scores for once-only fallers were mostly between those for non fallers and multiple fallers. Those who suffered recent fall-related fractures had significantly reduced tactile sensitivity and quadriceps strength and increased body sway. Postural stability was also impaired in patients taking psychoactive and/or anti-hypertensive medications. CONCLUSION: Tests of postural stability can identify, independently of age, individuals living in the community who are at risk of falls and fall-related fractures. PMID- 8202003 TI - Unlinked anonymous screening of antenatal patients for antibody to human immunodeficiency virus type 1 (HIV-1). AB - OBJECTIVES: To determine the prevalence of HIV-1 infection in the general community by using a target population (antenatal patients) as an indicator of infection, to monitor any change in the prevalence of HIV infection in this population and provide baseline information on heterosexual spread of HIV infection into this low prevalence population. PATIENTS AND DESIGN: Between January 1989 and January 1992, 4537 unlinked anonymous antenatal sera were tested in two study groups at Westmead Hospital. Repeatedly reactive sera were confirmed by western blot and other supplementary assays as appropriate. RESULTS: No significant change in the seroprevalence of HIV-1 infection was detected between the two study periods. Of the 2208 sera tested in 1989-1990, one (0.05%) was confirmed as positive and one (0.05%) gave a non-specific reaction by enzyme immunoassay (EIA). Of the 2329 sera tested in 1991-1992, there was one (0.04%) HIV-1 antibody positive serum, and two gave non-specific EIA reactions. These results were compared with three other sample populations tested at Westmead Hospital during the same period: linked antenatal patients, antenatal methadone clinic attendees and all women tested. CONCLUSIONS: Periodic anonymous testing of a sample antenatal population (combined with screening of high risk patients) is useful for monitoring the prevalence of HIV infection in these populations and estimating any future need for generalised screening. PMID- 8202004 TI - Herpes simplex virus type 2 infection of heterosexual men attending a sexual health centre. AB - OBJECTIVE: To identify risk factors, particularly circumcision status, associated with serological evidence of herpes simplex virus type 2 (HSV-2) infection of heterosexual men. DESIGN: A cross-sectional case-control study employing an anonymous delinked interviewer-administered questionnaire, clinical examination, and a type-specific serological test for HSV-2. PARTICIPANTS AND SETTING: Three hundred consecutive heterosexual male patients at a public sexually transmissible diseases (STD) clinic in Sydney, Australia. MAIN OUTCOME MEASURES: Associations between serological evidence of HSV-2 infection and history of genital herpes or contact with genital herpes, history of other common STDs, and demographic and behavioural factors such as age, education level, number of sexual partners and lack of circumcision. RESULTS: One hundred and ninety-four patients (64.7%) had antibodies to HSV-2 but only 24% of these gave a history of genital herpes. A history of genital herpes or sexual contact with genital herpes, reported total lifetime number of sexual partners, failure to complete high school and a history of non-gonococcal urethritis or genital warts were associated with serological evidence of HSV-2 infection at the univariate level. Neither increasing age nor lack of circumcision was associated with HSV-2 infection. Following multivariate analysis only the lifetime number of partners and failure to finish high school were significantly strong predictors of HSV-2 infection. CONCLUSION: This is the highest prevalence of HSV-2 infection ever detected in an Australian population and one of the highest recorded globally. As younger men were as commonly infected as older men, and an earlier (1985) study involving the same clinic yielded a lower prevalence, it appears that a high level of ongoing HSV-2 transmission is occurring among Sydney heterosexuals. Increased awareness of this fact could enhance safer sex campaigns. PMID- 8202005 TI - Lack of efficacy of single-dose prednisolone in moderately severe asthma. AB - OBJECTIVE: To assess the effectiveness of single-dose prednisolone in reducing the length of illness and hospital stay in children admitted with moderately severe asthma. DESIGN: A randomised, double-blind, controlled trial of a single dose of prednisolone in 64 children presenting with an acute attack of asthma with arterial oxygen saturation less than 93%. RESULTS: No significant differences in the rate of recovery of oxygen saturation, lung function measurements or duration of hospital stay were found. CONCLUSIONS: This study failed to confirm the benefit of a single dose of prednisolone in the management of children with acute severe asthma. PMID- 8202006 TI - Vaccine prophylaxis of Q fever. A follow-up study of the efficacy of Q-Vax (CSL) 1985-1990. AB - OBJECTIVES: To examine the efficacy of various batches of a formalin-inactivated whole cell Coxiella burnetti vaccine (Henzerling strain, Phase 1 [Q-Vax, CSL]) in the prevention of Q fever among abattoir workers. DESIGN AND SETTING: The study was a retrospective cohort survey of all employees at three South Australian abattoirs to determine the incidence of Q fever among vaccinated and unvaccinated employees during the period 1985 to 1990. RESULTS: There were two cases of Q fever among 2555 vaccinated employees of the three abattoirs, compared with 55 cases among 1365 unvaccinated employees. The two Q fever cases in vaccinated employees were within a few days of vaccination, before immunity had developed, and represented a coincidence of natural infection and vaccination. Protective efficacy was 100%, even with a batch of Q-Vax containing 20 micrograms/dose rather than the standard dose of 30 micrograms/dose. CONCLUSIONS: Vaccination was effective for at least five years, although it was uncertain whether this was due to the vaccine per se or to a combination of vaccine immunity reinforced by periodic natural exposure. PMID- 8202007 TI - Hospital practices influence the pattern of infective endocarditis. AB - OBJECTIVE: To identify factors contributing to infective endocarditis at a major teaching hospital. METHODS: Retrospective review of clinical records of patients diagnosed with endocarditis by standard case definitions with respect to causative organisms, clinical features and outcome. RESULTS: One hundred and ninety-three episodes of endocarditis seen between 1979 and 1992 at Westmead Hospital, Sydney, were reviewed. In the 174 cases where the causative organism was isolated, 75 (43%) were Staphylococcus aureus and 50 (29%) were viridans streptococci. Nosocomial acquisition and/or inter-hospital transfer accounted for 83 episodes; 48 (58%) S. aureus (P < 0.001) and nine (11%) viridans streptococci (P < 0.001). In cases from the local community, viridans streptococci were more common than S. aureus (37% versus 25%); these included 18 episodes (14 S. aureus) in intravenous drug users. CONCLUSION: We conclude that, compared with community acquired infections, the aetiology of endocarditis in a large teaching hospital is influenced strongly by the prevalence of nosocomial endocarditis and the need for interhospital transfer of complicated cases. PMID- 8202008 TI - Spot diagnosis. The burning millipede. PMID- 8202009 TI - Acacias and aesculapius. Professor Rembert Dodoens. PMID- 8202010 TI - A strategy to reduce inappropriate red blood cell transfusion. AB - OBJECTIVE: To evaluate the effectiveness of policies intended to decrease unnecessary packed red cell transfusions. DESIGN AND SETTING: The transfusion records of a 550-bed acute care facility were obtained and two six-month periods, one before and one after the introduction of new transfusion policies, were compared. RESULTS: Meaningful reductions were seen in crossmatch requests, number of units crossmatched and units transfused. After standardising for rising patient numbers, units transfused per 1000 admissions fell by 28.8%. Units crossmatched fell by slightly more than did units transfused, resulting in lower crossmatch-to-transfusion ratios, and indicating more effective use of resources. Total requests fell while "group-and-screen" requests rose, showing a shift toward more appropriate ordering in the face of increasing workload. CONCLUSIONS: The transfusion policies have succeeded in curtailing unnecessary transfusion practices. They included the lowering of "transfusion-triggering" haemoglobin levels, registrar or consultant approval of transfusions and enforcement of patient consent and chart documentation of transfusion indications, verified by the laboratory. The surgical blood ordering schedule was reviewed under the overall direction of the transfusion committee. A strong institutional commitment is required to lift the profile of blood transfusion. PMID- 8202012 TI - Inadvertent placement of advertisements. PMID- 8202011 TI - Inadvertent placement of advertisements. PMID- 8202013 TI - Type, frequency and distribution of Haemophilus influenzae in central Australian aboriginal children with invasive disease. PMID- 8202014 TI - Haemochromatosis diagnosed after dual energy x-ray imaging. PMID- 8202015 TI - Petrol sniffing down the track. PMID- 8202016 TI - Cannabis and suicide. PMID- 8202017 TI - Death caused by overheating in piglets susceptible to malignant hyperthermia. PMID- 8202018 TI - Solicitation of implant patients. PMID- 8202019 TI - Association of a complement allotype (C3F) with acute inflammatory responses to Candida albicans infection. PMID- 8202020 TI - Augmentin-associated jaundice. PMID- 8202021 TI - Evidence of HIV transmission in an Australian prison. PMID- 8202022 TI - Ankylosing spondylitis. PMID- 8202023 TI - Hepatitis B in urban Australian school children. PMID- 8202024 TI - Autonomous patients and medical professionalism. PMID- 8202025 TI - The choice of antibacterial drugs. PMID- 8202026 TI - Reactivity of varicella-zoster virus subunit antigens in enzyme-linked immunosorbent assay to sera from varicella, zoster, and herpes simplex virus infections. AB - Serological responses to varicella-zoster virus (VZV) subunit antigens, such as capsid, envelope, and soluble (S) antigens, in patients with VZV and herpes simplex virus (HSV) infections were studied by comparing with responses to virion (V) antigens using an enzyme-linked immunosorbent assay (ELISA). S antigen, prepared by concentrating supernatant of VZV or HSV type 1 (HSV-1)-infected cell culture fluid, reacted strongly to sera from patients with secondary infection but reacted poorly to those from patients with a primary infection of VZV or HSV. Antibody titers to VZV-S antigen persisted for a long period in patients with VZV infections. Patients infected with VZV showed antibody increase to HSV-1, when tested by complement fixation or complement-enhanced neutralization test, in cases with a history of prior HSV infection. However, such a cross-reaction was only observed to a minor extent in ELISA test using S antigen. S antigen reaction was stronger in secondary infections in tests with various subunit antigens. Almost no cross-reactivity was observed in an immunoblotting test with S antigen. Differentiation between infections with either varicella or zoster or HSV can be made by comparison of antibody responses to V and S antigens. PMID- 8202027 TI - Virulence factors and phenotypical traits of verotoxigenic strains of Escherichia coli isolated from human patients in Germany. AB - Fecal isolates of Escherichia coli which were collected from human patients in different parts of Germany between 1985 and 1992 were examined for production of verotoxins (VT). Among 2165 isolates 54 (2.5%) verotoxigenic E. coli (VTEC) were found. The 54 VTEC belonged to 13 different serotypes, 46 (85.2%) of these were enterohemorrhagic E. coli (EHEC) types as O157:H7, O157:H-, O145:H-, O111:[H8] and O26:[H11]. Of the 54 VTEC 50 (92.6%) hybridized with one or both of the DNA probes specific for VT1 and VT2. The 4 VTEC strains which were negative for VT1 and VT2 differed from all other VTEC by many phenotypical trains such as serotype, production of alpha-hemolysin and absence of EHEC-plasmid and "attaching and effacing" (eae)-specific DNA sequences. In contrast, VTEC which were positive for VT1, VT2 or both were frequently positive for eae sequences (92.0%), EHEC-plasmids (90.0%) and for production of enterohemolysin (88.0%). With enterohemolysin as an epidemiological marker more VTEC strains (81.5%) could be identified than with others such as the absence of beta-glucuronidase activity (61.1%) or non-fermentation of sorbitol (48.1%). Case reports were available for 42 of the 54 VTEC strains. The clinical presentation of 42 cases with VTEC ranged from uncomplicated diarrhea to severe diseases as hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS). However, bloody diarrhea, HC and HUS were more associated with the O157 group than with other VTEC groups. PMID- 8202028 TI - Differentiation in virulence patterns of Escherichia coli possessing eae genes. AB - In this study 98 Escherichia coli strains which belonged to traditional enteropathogenic (EPEC) serotypes and 82 enterohemorrhagic E. coli (EHEC) strains were screened by polymerase chain reaction (PCR) for the presence of E. coli attaching and -effacing (eae) genes. These strains were also hybridized with the enteropathogenic adherence factor (EAF) probe and examined in the fluorescence actin staining (FAS) test. The results obtained from the individual strains demonstrated that all 26 class I EPEC with localized adherence to HEp-2 cells carried EAF and eae genes. In contrast, of 72 EPEC strains with no or diffuse adherence only 1 strain was EAF positive and 6 strains had eae. Of 82 EHEC strains a total of 75 carried eae sequences. Of considerable interest, 15 of 21 E. coli strains that lost their slt genes during subcultivation were found to be eae positive. As controls a total of 53 enterotoxigenic and enteroinvasive E. coli, and 125 E. coli strains from the normal flora were investigated and all displayed negative results in the eae-PCR. From the 201 strains comprising classical EPEC serotypes, EHEC and E. coli with lost slt genes, a total of 126 displayed a positive FAS test and 122 reacted in the eae-PCR. Only 4 strains were FAS test positive but eae-PCR negative. Our data indicate that E. coli strains possessing the eae genes are heterogenous with respect to their virulence determinants. Loss of virulence plasmids and phage-encoded slt genes either in the host or during storage may contribute to this heterogeneity. The eae-PCR detected all class I EPEC and 91.5% of the EHEC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202029 TI - Immunoglobulin-binding FcrA and Enn proteins and M proteins of group A streptococci evolved independently from a common ancestral protein. AB - Significant sequence homology between M proteins and immunoglobulin (Ig)-binding proteins of group A streptococci suggests that these proteins arose by gene duplication followed by the development of functional diversity due to mutations and intragenic recombinations. The deduced sequence of multiple Ig-binding proteins and M proteins were compared to distinguish between two evolutionary models. Did these functionally distinct genes originate in the distant past from duplication of a common ancestral gene and then functionally evolve independently or did they evolve more recently, one from the other by duplication of a fixed gene? Multiple alignments of conserved sequences of these proteins are consistent with the former hypothesis. Comparison of N termini of Ig-binding proteins revealed less diversity than that of the M proteins' N termini, suggesting that these proteins are under less selective pressure to change. PMID- 8202031 TI - LCH-I: a randomized trial of etoposide vs. vinblastine in disseminated Langerhans cell histiocytosis. The Histiocyte Society. AB - An international randomized trial in Langerhans cell histiocytosis (LCH) has been initiated by the Histiocyte Society. This report reviews the rationale, design, and progress of LCH-I, which compares etoposide (VP-16) and vinblastine in the treatment of disseminated LCH. Data on the risk of etoposide-associated (therapy induced) malignancy, in the setting of histiocytosis, are reviewed. The available evidence leads to the recommendation that the study of etoposide in LCH should be continued. PMID- 8202030 TI - Immunoblot using recombinant antigens derived from different genospecies of Borrelia burgdorferi sensu lato. AB - Immunodominant proteins are variable in molecular and antigenic structure among different genospecies of Borrelia burgdorferi sensu lato. We have recently developed an immunoblot using five recombinant antigens: the chromosomal-encoded B. burgdorferi proteins p100, the flagellin and an internal flagellin fragment thereof, and the plasmid-encoded outersurface proteins A (OspA) and C (OspC). In the present study the same antigens (derived from strain PKo, genospecies B. afzelii) were compared with the homologous recombinant proteins from strain B31 (genospecies B. burgdorferi sensu stricto) and with OspA, OspC and the internal flagellin fragment from strain PBi (genospecies B. garinii). Patients with neuroborreliosis (n = 28) and patients with acrodermatitis chronica atrophicans (n = 20) were investigated in the IgG immunoblot; the IgM immunoblot was performed only in patients with neuroborreliosis. There was a small increase in the detection rate of OspA-specific IgG or IgM antibodies using the different variants of recombinant OspA; however, OspA remained an insensitive antigen for antibody detection in Lyme borreliosis. The same was true to OspC-specific IgG antibodies. The sensitivity of OspC, which is the immunodominant antigen for IgM antibody detection, could not be increased using recombinant antigens derived from different strains. However, some sera which were negative in the recombinant immunoblot reacted with OspC in the conventional immunoblot using B. burgdorferi whole cell lysate as antigen. The most unexpected finding was the high degree of immunological heterogeneity of the internal flagellin fragments: IgG antibodies were detected in 18 of 48 patients using B31 fragments, in 25 of 48 using PKo fragments, in 23 of 48 using PBi fragments versus 33 of 48 when the three recombinant proteins were combined. PKo-derived fragments were more sensitive for antibody detection in patients with acrodermatitis chronica atrophicans, B31- and PBi-derived fragments for antibody detection in patients with neuroborreliosis. This is in agreement with the fact that isolates from patients with neuroborreliosis are predominantly belonging to the genospecies B. burgdorferi sensu stricto and B. garinii. For detection of IgM antibodies in sera from patients with neuroborreliosis, recombinant internal fragments derived from strains B31 and PBi were more sensitive than the PKo-derived fragment. The best discrimination between neuroborreliosis sera and control sera was achieved when the IgM blot was performed using recombinant internal flagellin fragments derived from strains PKo and PBi and OspC derived from B31 or PKo. PMID- 8202032 TI - Liver function studies in children with acute lymphocytic leukemia after cessation of therapy. AB - We investigated liver function in 27 children with acute lymphocytic leukemia (ALL) after cessation of therapy. Induction therapy consisted of prednisolone+vincristine (VP regimen) alone (16 patients) or with addition of daunorubicin (4 patients) or L-asparaginase (7 patients). Patients treated with VP regimen received short courses of VP regimen every 12 weeks for the first year of maintenance. Twenty-five patients remained in first complete remission and had completed 3-year maintenance therapy with methotrexate (MTX) and 6-mercaptopurine (6-MP) 1-7 years prior to this study. Twenty-three patients had received transfusions of packed red blood cells or fresh whole blood (1-11 units; median: 2 units) but none had evidence of either hepatitis B or hepatitis C. Alanine aminotransferase (ALT), which was measured every 3 months during maintenance therapy, had values more than three times the upper limit of the normal range in 25% of the measurements in more than half of the patients. However, by 3 months after the completion of maintenance therapy, ALT had normalized in all patients and remained normal in all but two patients until the time of this study. Serum bilirubin, serum albumin, and prothrombin time were all within normal limits. Fasting and 2-hour postprandial total serum bile acids were high in 5 of 13 patients and in 6 of 13 patients, respectively. The ratio of cholic acids+deoxycholic acids to chenodeoxycholic acids+lithocholic acids was below 1 in all but two patients, whereas this ratio was above 1 in all controls. Our bile acid profile results indicate the necessity of careful long-term follow-up of survivors of ALL treated with hepatotoxic chemotherapy during childhood. PMID- 8202033 TI - Neuropsychological evaluation of children with intracranial tumors: impact of treatment modalities. AB - Antineoplastic treatment has a deleterious effect on intellectual functions, which is mainly attributable to radiotherapy. With the object of determining the neuropsychological disturbances associated with brain irradiation in the child, and to try to differentiate them from the effects caused by the other types of treatment (surgical and chemotherapy) as well as from the effects of the tumor itself, a cross-sectional study was carried out in 25 survivors of medial edge intracranial tumors. In order to monitor the effect of systemic chemotherapy on the cognitive functions, and the effect of prolonged absence from school, two control groups were formed, one made up of subjects treated with chemotherapy for extracranial tumors, and the other of patients with non-malignant chronic disease. Neuropsychological functions were measured using the Spanish version of the Wechsler scale, as well as the following tests: Spreen-Benton, ITPA and TALE scales, Yuste Memory Test, Thurstone Attention Test, and the Rey Complex Figure. In addition to a progressive decline found in the full scale intelligence quotient in children irradiated for intracranial tumors, variance analysis showed that these patients deteriorate mainly in visual attention and memory, but also significantly in verbal fluency and in the Performance Intelligence Quotient and all its subtests, when compared to the control groups. Visual attention and the Wechsler Picture Arrangement and Block Designs, were the tests whose decline correlated with the total radiation administered. The article relates this specific neuropsychological injury with the total brain irradiation dose but also with the structures located in the cone-down fields of irradiation to boost regions in the middle edge intracranial content. PMID- 8202034 TI - Cytogenetic abnormalities of small round cell tumours. AB - Between 1987 and 1991, cytogenetic studies were carried out on small round cell tumours of 68 patients from the Northern Health Region of England. Clonal chromosome abnormalities were found in 30, comprising 15 neuroblastomas, 7 Ewing's tumours, 7 rhabdomyosarcomas, and 1 granular cell tumour. Characteristic rearrangements were found in five cases of Ewing's tumour [all with translocation t(11;22) (q24;q12)] and in four cases of rhabdomyosarcoma [all with evidence of translocation t(2;13) (q35-37;q14)]. In one case of Ewing's tumour and three of rhabdomyosarcoma, the cytogenetic findings were important in diagnosis. Within the neuroblastomas, examples were found of hyperdiploidy, 1p rearrangements, double minute chromosomes, and homogeneously staining regions, but too few cases were available for prognostic associations to be assessed. Our findings confirm the diagnostic importance of chromosome abnormalities in small round cell tumours and indicate that cytogenetic analysis should be an intrinsic part of the initial investigations of all patients with such tumours. PMID- 8202035 TI - Negative 123-meta-iodobenzyl-guanidine imaging in Ewing's sarcoma of bone. AB - The role of radiolabeled meta-iodobenzyl-guanidine (mIBG) is established in the detection and the staging of neuroblastoma. We designed a study of mIBG scanning for patients with Ewing's sarcoma, a tumor for which a neuroectodermic origin has been proposed. We explored 15 children with round cell sarcoma of bone by a whole body scan carried out 24 hours after injection of 123-I mIBG. No patient demonstrated significant uptake either at the site of the primary or at the sites of metastases. These results suggest that despite its neural histogenesis Ewing's sarcoma is a member of the nonneuroblastoma neural crest tumors, which does not produce or store adrenergic metabolites. PMID- 8202036 TI - Hormonal treatment in pregnancy: a possible risk factor for neuroblastoma. AB - In the last 4 years, 24 cases of neuroblastoma were treated in the Pediatric Hematology-Oncology Unit at the Chaim Sheba Medical Center, 8 of whom were under 1 year of age. Four of them were the product of a pregnancy-induced or preserved by gonadotropins, clomiphene citrate, or progestational hormones. These drugs are known to produce a higher than normal level of estradiol or progesterone in the early stages of pregnancy. Our observation led to the hypothesis that high levels of progestational hormones given during pregnancy are a risk factor for neuroblastoma in infancy. PMID- 8202037 TI - Acute tumour lysis syndrome complicating treatment of stage IVS neuroblastoma in infants under six months old. AB - Acute tumour lysis syndrome (ATLS) is a common complication of the treatment of haematopoietic malignancies. It is also well recognized in many nonhaematopoeitic malignancies of adults. There are very few reports of the syndrome occurring during therapy for the nonhaematopoeitic malignancies of childhood, and none has previously been reported in the treatment of neuroblastoma. We report the cases of four patients presenting to The Hospital for Sick Children (HSC) between 1985 and 1992 who developed ATLS during treatment for stage IVS neuroblastoma. ATLS is a significant risk in patients undergoing therapy for stage IVS neuroblastoma, particularly where this has been delayed. PMID- 8202038 TI - Hypertrophic pulmonary osteoarthropathy in a child with thymic carcinoma: an unusual presentation in childhood. AB - We report here a case of intrathoracic undifferentiated carcinoma in the thymus with hypertrophic pulmonary osteoarthropathy in a 13-year-old girl. The association of the two conditions is very rare. PMID- 8202039 TI - Low grade malignant hemangioendothelioma of bone: a disease potentially curable with radiotherapy. AB - This is a case of a young woman with a low grade malignant hemangioendothelioma of bone, who is considered cured after more than 8 years of follow-up post radiotherapy. This patient demonstrates that, despite the characteristic multifocality of this rare tumor, treatment with radiotherapy alone can be curative. PMID- 8202040 TI - Primary cardiac angiosarcoma: a case report and review of therapeutic options. AB - A 45-year-old black patient presented with right-heart failure. Echocardiography showed a large tumor mass in the right atrium and a debulking procedure was performed. Histological and immunohistochemical studies revealed a high grade angiosarcoma infiltrating the myocardium and extending to the pericardial surface. Metastatic work-up showed no evidence of dissemination. The patient made an uneventful postsurgical recovery and was treated with chemotherapy, consisting of epidoxorubicin and dacarbazin. Following chemotherapy, echocardiographic re evaluation failed to show any residual tumor in the right atrium. At present, one year following diagnosis, the patient is alive with no evidence of disease. Therapeutic options of primary cardiac angiosarcoma are reviewed. PMID- 8202041 TI - Isolated bone relapse during hematologic remission in childhood acute lymphoblastic leukemia: report of a metatarsal relapse and review of the literature. AB - An 11-year-old boy with prior bone marrow and testicular relapses of his acute lymphoblastic leukemia (ALL) developed an isolated metatarsal bone relapse during complete hematologic remission 10 months after completion of chemotherapy. Although there was no radiographic or histologic evidence of additional occult leukemia, the polymerase chain reaction (PCR) technique detected a leukemic clone in both his bone marrow and metatarsal. A literature survey revealed only 10 reported cases of isolated bone relapse occurring during complete bone marrow remission in childhood ALL. Most of these patients had prior bone marrow or extramedullary relapses. The majority experienced subsequent relapses after their isolated bone recurrence. We report a case of isolated bone recurrence, review all previously reported cases, and suggest that PCR elucidation of clonal disease may provide a better understanding of these extremely rare extramedullary events. PMID- 8202042 TI - Late recurrent metastasis in Wilms' tumour. AB - Recurrence of Wilms' tumour after 5 years of disease-free survival is rare. We present the case of a 26-year-old man who had been diagnosed of Wilms' tumour at the age of 6 years treated by surgery, chemotherapy, and radiotherapy and who remained disease free for 8 years, after which lung metastases were detected. Second complete remission was attained with surgery and chemotherapy and 20 years after initial diagnosis he again presented with lung metastases, similarly achieving complete remission with surgery and second-line chemotherapy. The clinical and biological aspects of late metastasis in this neoplasm are discussed. PMID- 8202043 TI - Primary osteosarcoma of the cervical spine: a pediatric case report and review of the literature. AB - A 4 1/2-year-old girl with a primary osteosarcoma of the seventh cervical vertebra, treated by surgery and chemotherapy, and who is off therapy for 24 months with no evidence of disease is presented and the literature reviewed. PMID- 8202044 TI - Langerhans cell histiocytosis and etoposide: risks vs. benefits. PMID- 8202045 TI - Treatment strategy for disseminated Langerhans cell histiocytosis. DAL HX-83 Study Group. AB - Treatment of Langerhans cell histiocytosis (LCH) remains problematic. To test the hypothesis that rapid initiation and long-term continuation of chemotherapy can improve survival and reduce recurrence and late consequences of disseminated LCH, we have completed a prospective clinical trial (DAL HX-83). One hundred six newly diagnosed patients were stratified into three risk groups (A: multifocal bone disease [n = 28]; B: soft tissue involvement without organ dysfunction [n = 57]; C: organ dysfunction [n = 21]). All patients received an identical initial 6-week treatment (etoposide [VP-16], prednisone, and vinblastine), and continuation treatment for 1 year, slightly adapted according to stratification at diagnosis. It included oral 6-mercaptopurine and eight pulses of vinblastine and prednisone for all patients, plus VP-16 in group B and VP-16 and methotrexate in group C. Eighty-nine percent and 91% of patients in groups A and B and 67% of the most severely affected group C, achieved complete resolution of disease. The speed of resolution was rapid (median 4 months) and independent of disease severity. The frequency of recurrence after initial resolution was low (12%, 23%, and 42% in groups A, B and C); overall fully 77% of patients have remained free of recurrence. Permanent consequences developed after diagnosis in 20% of the patients. Diabetes insipidus after initiation of treatment occurred in only 10% of patients. Mortality (9%) was limited to patients of groups B (two patients) and C (eight patients). Finally, among the 106 patients treated by DAL HX-83 none have developed a malignancy (median follow-up 6 years, 9 months). The shorter duration of active disease, low rate of recurrence and permanent consequences, and improved survival among patients with poor prognosis support the strategy of rapid initiation of a predefined prolonged treatment upon the diagnosis of disseminated LCH. PMID- 8202046 TI - Acute leukemia in association with Langerhans cell histiocytosis. AB - Langerhans cell histiocytosis (LCH) and malignancy occurring in the same individual is unusual and has generally been the subject of isolated case reports. To better define the occurrence of these events a registry of cases with synchronous or asynchronous LCH and malignancy was developed with the cooperation of the Histiocyte Society. In 1991 the Histiocyte Society surveyed its members requesting information on cases in which LCH was associated with malignancy. The questionnaire was mailed to all members of the society and specifically requested information on the clinical and laboratory features of the cases, disease evolution, and response to therapy. Retrospective reporting was allowed. With this initial data, an ongoing registry of LCH patients with associated malignancy was begun of such cases, including evolution and response to therapy. Twenty seven patients were enrolled during the first year of registry, of whom 4 patients had the association of LCH with a malignant lymphoma and 10 cases had an association of LCH with other types of solid tumor. The remaining 13 patients had the association of LCH with acute leukemia. In five cases, LCH was associated with acute lymphoblastic leukemia FAB L1 (ALL). In four cases the ALL preceded the LCH by 6 months to 1 year. In four of five patients the LCH was localized; in two instances the LCH was treated with chemotherapy. In all cases the leukemia was treated according to local standard ALL protocols and in one case autologous bone marrow transplantation (ABMT) was performed at relapse. Three patients are free of leukemia, one of whom has persistent localized LCH of the skin. Two patients died of the ALL, one of whom was free of the LCH at the time of death. In eight instances LCH was reported in association with acute myeloid leukemia (AML). Six of these patients had a generalized form of LCH. In seven the diagnosis of LCH preceded the diagnosis of leukemia by more than 2 years (median 4 years). In the remaining patient both diagnoses were made concurrently. In all seven cases in whom LCH was the initial diagnosis the treatment consisted of chemotherapy and/or radiotherapy. Seven patients died from the AML, five without evidence of LCH. The temporal patterns of the LCH-ALL and LCH-AML associations are distinct with ALL usually preceding the diagnosis of LCH and AML succeeding it.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8202047 TI - Therapy-related acute myeloid leukemia following treatment with epipodophyllotoxins: estimating the risks. AB - In the past decade, therapy-related acute myeloid leukemia (t-AML) following treatment with regimens that include inhibitors of topoisomerase-II (TOPO-II) has been reported with increasing frequency. These cases of t-AML generally have a shorter latency period than t-AML following alkylator therapy, are associated with chromosomal translocations (especially involving chromosome band 11q23), and usually present as M4 or M5 FAB subtype. Although the epipodophyllotoxins (etoposide and teniposide) have been most often implicated, similar cases of t AML occur following therapy with other classes of Topo-II inhibitors (e.g., anthracyclines). There is wide variation in published studies in the estimates of risk of t-AML following epipodophyllotoxin therapy. These varying estimates may reflect a number of factors, including: small sample size leading to large confidence intervals around risk estimates; varying susceptibility of different patient populations; varying schedules of epipodophyllotoxin administration; different cumulative doses of epipodophyllotoxins; and administration of epopodophyllotoxins with additional agents that may alter the leukemogenic effect of the epipodophyllotoxins. Available data suggest that children with acute lymphocytic leukemia (ALL) treated with high cumulative doses of epipodophyllotoxins using either weekly or twice-weekly schedules of administration have a relatively high risk of developing t-AML (5-12% cumulative risk). On the other hand, germ cell patients treated with relatively low cumulative doses of etoposide (usually 1,500-2,500 mg/m2) appear to have a low risk for developing t-AML. There is inadequate experience at this time with higher cumulative doses of etoposide (e.g., 4,000-5,000 mg/m2 as used for pediatric solid tumors) given on a daily x 5 schedule to allow estimates of risk to be developed for this schedule and cumulative dose. The Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan designed to obtain reliable estimates of the risk of t-AML following epipodophyllotoxin treatment. Twelve Cooperative Group clinical trials that use epipodophyllotoxins at either low (< 1,500 mg/m2), moderate (1,500-3,999 mg/m2), or higher cumulative doses (> 4,000 mg/m2) are being prospectively monitored for cases of t-AML occurring among patients entered onto the trials. PMID- 8202048 TI - Acute myeloid leukemia in patients treated for rhabdomyosarcoma with cyclophosphamide and low-dose etoposide on Intergroup Rhabdomyosarcoma Study III: an interim report. AB - The early occurrence of five cases of acute myeloid leukemia (AML) in children treated for primary rhabdomyosarcoma on the Intergroup Rhabdomyosarcoma Study III (IRS III) has prompted this report. These patients received cyclophosphamide and four received etoposide in addition to other agents. There were 1,062 eligible patients entered on IRS III between 1984 and 1991. Following surgery, treatment consisted of multiagent chemotherapy and radiotherapy in select clinical groups. Median follow-up time is 3.7 years (range 0-7.4 years). Incidence densities and odds ratios for AML were calculated for various treatment groups. Five cases of secondary AML have been reported through August 1992. A single case of osteogenic sarcoma was reported in the same period and a patient with myelodysplastic syndrome has occurred since that time. Median time to development of AML was 39 months. Incidence density of AML for patients receiving neither cyclophosphamide nor etoposide was 0, for those receiving cyclophosphamide but no etoposide it was 7.6, and when both agents were given, it was 51.6. The odds ratios of AML for the latter two groups indicated a risk of AML which was seven times higher in the patients who received both agents. A history of breast cancer was present in all five families of patients with AML and several other cancers had occurred in three families. Preliminary analysis suggests a possible causal role for low-dose etoposide in addition to that assumed for cyclophosphamide in the early development of AML among pediatric patients treated for rhabdomyosarcoma. PMID- 8202049 TI - Cytosolic pH regulation in osteoblasts. AB - The process of bone formation depends on an optimal alkaline pH in the extracellular milieu surrounding the osteoblast. To the extent that ionic composition of an extracellular environment is determined by events taking place inside the cell, it is conceivable that the pH in the fluid outside the osteoblast is affected by cytosolic pH (pHi) regulation by these cells. Under HEPES-buffered conditions, the main pH regulatory mechanism is the ubiquitous acid-extruding mechanism, Na+/H+ exchange. However, under the more physiologic HCO3- environment, one can identify three additional acid-bone transporters: Na(+)-independent Cl-/HCO3- exchanger, Na+(HCO3-)3 cotransporter, and HCO(3-) conductive pathway. In addition to their role in regulation of pHi in the osteoblast, these transporters also play a role in volume regulation of these cells both under hypertonic conditions (regulatory volume increase) and during osmotic swelling (regulatory volume decrease). Second messengers produced by calciotropic hormones (e.g. cytosolic Ca2+, cAMP) regulate the activity of Na+/H+ exchanger and Cl-/HCO3- exchanger. PMID- 8202050 TI - Osteoclastic acid transport: mechanism and implications for physiological and pharmacological regulation. AB - In order to solubilize bone mineral and degrade the organic matrix of bone osteoclasts must secrete 1-2 protons for every Ca2+ liberated. This transport is a major metabolic activity of osteoclasts requiring an electrogenic H(+)-ATPase, a conductive chloride channel, a chloride-bicarbonate exchanger, carbonic anhydrase, and functional/morphological polarization of the cell. The osteoclast H(+)-ATPase is electrically coupled to a chloride channel in the ruffled membrane as are similar transport activities found in acidic intracellular vesicles, but the vanadate sensitivity of the osteoclast proton pump is intermediated between that of the E- and v-type proton pumps. The carbonic anhydrase and chloride bicarbonate exchange provide an interface with pH regulation and integrate bone resorption into systemic acid-base balance. With the molecular mediators of bone resorption being known we may consider the control of bone resorption with an eye to mechanism and specificity that has not previously been possible. The effects of systemic acidosis to increase bone resorption and the effects of carbonic anhydrase deficiency are consistent with our mechanism of osteoclast ion transport. PMID- 8202051 TI - Acidosis and bone. AB - Acidosis has important effects on the bone mineral which can be investigated utilizing neonatal mouse calvariae in organ culture. When calvariae are cultured for 3 h in physiologically acidic medium produced by a reduction of the bicarbonate concentration, a model of acute metabolic acidosis, there is net calcium efflux from bone in addition to net proton influx into bone which lessens the severity of the acidosis. Utilizing a high resolution scanning ion microprobe to study the bone during acidosis we have found that the protons exchange for sodium and potassium on the bone surface. In acute experiments the calcium efflux is the result of mobilization of carbonated apatite through an alteration in the physicochemical driving forces for bone mineral accretion and dissolution. In the more chronic cultures (greater than 48 h) metabolic acidosis induces calcium efflux by stimulating osteoclastic bone resorption and inhibiting osteoblastic bone formation. When calvariae are cultured for 3 h in acidic medium produced by an increase in the partial pressure of carbon dioxide, a model of respiratory acidosis, there is also calcium efflux; however, at the same decrement in pH the net flux is far less than that observed during metabolic acidosis. During acute respiratory acidosis there is no measurable influx of protons into bone and during chronic studies there is no measurable calcium efflux. PMID- 8202052 TI - Role of bone in acid-base regulation. Introduction. PMID- 8202053 TI - The effect of parathyroid hormone and other metabolic factors on extrarenal acid buffering. AB - Parathyroid hormone (PTH) is an 84-amino acid, a polypeptide hormone which acts in many tissues. In the human there are many clinical examples of both primary and secondary PTH excess states; while deficiency states also occur, they are far less common. This manuscript reviews the effects of PTH on extrarenal acid buffering and discusses the possible mechanisms which are involved. PMID- 8202054 TI - The role of parathyroid hormone and vitamin D in acid excretion and extrarenal buffer mobilization. AB - Parathyroid hormone (PTH) and vitamin D are involved in the maintenance of acid base homeostasis by enhancing urinary acid excretion and mobilizing extrarenal buffer present in bone. Acidosis may alter hormonal effect and metabolism. Conclusions reached from experimental and clinical states of hormonal deficiency and excess must take into account differences due to species and methodologies. This paper critically reviews the role of PTH and vitamin D on acid-base metabolism. PMID- 8202055 TI - The physicochemical structure of bone: cellular and noncellular elements. AB - Bone responds to systemic acid base perturbations through an ionic exchange with the systemic extracellular fluid which, in its extreme form, culminates in dissolution of the skeletal tissue as observed in chronic acidotic states. As a major reservoir for the body stores of calcium, phosphorus, carbonate, citrate, magnesium and sodium the bone may use these ions in order to buffer massive loads of protons during acute metabolic acidosis. The total skeletal mass consists of two components: (1) an organic unmineralized matrix which includes mainly type 1 collagen and which comprises about one third of total bone weight and (2) the inorganic mineral phase of bone which constitutes about two thirds of the skeleton and is mainly composed of hydroxyapatite crystals (the main form of bone mineral). States of chronic metabolic acidosis lead to a gradual and progressive resorption of both the organic and inorganic components of bone. This process is carried out both by a direct physicochemical effect of the excess protons and through activation of the two main bone cell types, the osteoblasts and osteoclasts. In order to fully comprehend the nature of bone-systemic circulation interface, it is essential to understand the microanatomy and the physicochemical structure of bone. PMID- 8202056 TI - Metabolic acidosis and bone disease. AB - Bone is the largest repository base in the body. Prolonged acid retention requires continuous buffering of acid if the organism is to survive. This paper discusses the role of bone buffering under both normal and altered conditions of acid-base homeostasis. We place particular emphasis on the roles of PTH and vitamin D in this process. We also discuss bone abnormalities in renal tubular acidosis and chronic renal failure. PMID- 8202057 TI - The role of chronic anion gap and/or nonanion gap acidosis in the osteodystrophy of chronic renal failure in the predialysis era: a minority report. AB - Chronic renal failure (CRF) due to (1) glomerulopathies, vascular and tubulointerstitial disorders, and (2) chronic nonazotemic renal tubular disorders creates sustained acidosis in the untreated state. Number 1 represents a mixture of anion and nonanion gap acidosis and number 2 a pure nonanion gap acidosis. There remains significant uncertainty as to the role of the acidosis (CRF) in the associated osteodystrophy. In general, little attention has been given to this subject in recent monographs. It is the purpose of this review ('minority report') to 'reexamine' the information available on this subject in humans and animals. The author has concluded that the chronic metabolic acidosis of CRF may well contribute to the development and maintenance of the osteodystrophy, and that its treatment should be included along with the other modalities of therapy. The subject is not a 'dead issue' but one definitely deserving further investigation. The response of the skeleton to acid loads clearly represents another 'trade-off' in ion metabolism in CRF. PMID- 8202058 TI - [Anatomic-functional relationships between the motor systems and the sleep wakefulness systems]. AB - The present paper deals with relationships between neural systems which control motor behaviour (pyramidal and extrapyramidal) and sleep-wakefulness states (in particular the reticular formation). We examined successively their anatomical and neurochemical substrates, electrophysiological and functional motor alterations depending on ascending and descending influences from brain stem during the sleep-wakefulness cycle. These data suggest that sleep-wake states result from the modulation of excitability in neuronal pools and that each state results from the co-ordinated working of several functionally different neuronal pools. Thus, each state could be understood as a sum of behavioural events depending on a neural network. We hypothesized that abnormal motor events occurring specifically during a sleep state could result from motor structures abnormally recruited in neural networks specifically involved in this sleep state. PMID- 8202059 TI - [The restless leg syndrome: a condition associated with periodic or aperiodic slowing of the EEG]. AB - There are several new developments with regard to semiology, diagnosis, physiopathology and the treatment of restless leg syndrome (RLS). We present here the hypothesis that motor manifestations of the RLS are synchronous to slowing of the cortical activity as measured by the spectral analysis of the EEG. When the subject is resting in bed with his leg outstretched, slowing of the EEG is observed, which could be periodic at the frequency of approximately 1 every 20 seconds or sustained. Leg movements can be periodic at the frequency of approximately 1 every 20 seconds or sustained. Leg movements can be periodic or aperiodic accordingly. On the contrary, periodic leg movements in sleep (PLMS) occur in close temporal relationship with periodic arousal. These results raised the hypothesis that leg movements (RLS and PLMS) may appear at a critical level of cortical activation. This level is reached during sleepiness in the awake subject or during periodic micro-arousal when the subject is asleep. Other results suggest that these periodic changes in the level of cortical activation may also modulate other abnormal motor behavior in sleep such as rhythmic masticatory muscles activity as seen in sleep bruxism. The same mechanism may also be involved in setting the duration of apneic episodes during slow-wave sleep. PMID- 8202060 TI - [Maturation of generalized motility, spontaneous during sleep, from birth at term to the age of 6 months]. AB - This work analysed the evolution of generalized motility from normal birth (39 to 40 weeks of gestational age) to six months of age, in 73 healthy infants during sleep, according to age. Sleep polygraphic recordings were performed in the morning; body movements were recorded with piezo-electric accelerometers. Our results showed that the number of movements per sleep hour was higher in active sleep (AS) as compared to quiet sleep (QS) whatever the age although the difference was less important in neonates (P < 0.05) than after one month of life (P < 0.001). The number of movements and the percentage of time spent in movements decreased with age; however in QS these parameters decreased sharply from birth to one month and a half but then did not significantly differ; in AS they became progressively lower. There were no statistically significant differences in the duration of body movements between sleep states in each age group; their mean duration became shorter from birth to six months of age (in AS P < 0.0001 and in QS P < 0.05). The distributions of the number of movements throughout the sleep stage were different according to sleep state and age. The movements were equally distributed during AS whatever the age and in the neonate group during QS; in older infants, the number of movements increased at the beginning and at the end of QS stages. During the first six months of life, spontaneous motility during sleep was inhibited, however, this process differed in quiet and active sleep. The relationship between body movements and sleep stages' organisation became closer during maturation. PMID- 8202061 TI - [Movement disorders during sleep: attempt at classification]. AB - We suggest a classification for abnormal motor behavior during sleep based upon clinical and research studies. Abnormal motor behaviors are classified into four types: aperiodic myoclonic contractions, periodic and stereotype movements, complex and disorganized motor behaviors, complex and organized motor behaviors. Examples for each type are given to support the classification. PMID- 8202062 TI - [Rhythms of falling asleep persisting in adults. Two cases without mental deficiency]. AB - Nocturnal rhythmic movements (jactatio capitis nocturnus, JCN) are very frequent in young children but persist only rarely in adults; studies including sleep recordings are exceptional in those cases. We report two new cases of young adults with JCN persisting since the first year of life, associated with restless sleep and diurnal sleepiness. Several episodes of JCN were recorded in each of the two patients; they always occurred after a period of paradoxical sleep, the waking phase preceding the rhythmic movements which are sometimes very short (1 s). The pathophysiology of adult JCN is discussed as a behavioral disorder of sleep onset conditioning or a disorder of sleep maintenance. PMID- 8202063 TI - [Rhythm of paradoxical sleep in an adult]. AB - Adults rarely present with rhythmic movement disorders in the Sleep Laboratory. We report the case of a 34 year-old woman, in good health, with a complaint of chronic body rolling during sleep and fatigue. Polysomnographic and video recordings showed head and body rhythmic movements, mainly during REM sleep. The contribution of severe psychopathology or neurological disorder was ruled out with personality testing, structured psychiatric interview and neurological examination with EEG, cerebral CT, MRI, and PET scans. PMID- 8202064 TI - The children: still at risk. PMID- 8202065 TI - Legislation is messy, but we need to be there.... PMID- 8202066 TI - The financial impact of managed care on the physician's practice. PMID- 8202067 TI - Unsafe driving behaviors and hospitalization. AB - The medical costs associated with motor vehicle crashes are difficult to measure. Most attempts have used crash data and cost data that are only indirectly related to each other or have followed patients in a few hospitals or trauma centers. These studies produce localized estimates or rough national estimates of limited use to policy makers. The result has been a dependence on more readily available mortality data, such as the Fatal Accident Reporting System, to guide automotive safety efforts. The limitations of mortality data and the increasing sophistication of medical care data bases have resulted in a strong interest in obtaining crash-linked morbidity data. Hence, in 1993, the National Highway Traffic Safety Administration (NHTSA) awarded the Missouri Department of Health and six other applicants grants to link automotive crash records to statewide ambulance trip, outpatient care, hospitalization and mortality records. By identifying an individual across multiple data sets, states would be able to determine directly the relationship of driver behaviors and crash characteristics to hospitalization rates and other medical outcomes. Examination of hospital pay source information would expose the toll of automotive crashes on public tax dollars. Having recently completed the record linkage phase of this project, Missouri Department of Health staff are beginning to analyze the impact of automotive crashes on health care costs in Missouri. In this report, three unsafe driving behaviors, failure to use a safety device (seatbelts and motorcycle helmets), driving under the influence of alcohol, and speeding, are related to the risk of hospitalization or death, hospital costs, and expected pay source. PMID- 8202068 TI - Decision support systems: fact and fiction. AB - Computers perform tasks daily that aid people in the completion of their duties; computers help drive cars, cook food, entertain, and support our decision making processes. Often a silent partner, the computer is involved in tasks that a health professional provides. Modern ECG machines, infusion pumps, blood analyzers, ventilators, and imaging machines contain computers that aid in the use of these devices. Though not traditionally considered decision support systems, these diagnostic systems support the decision making process in health care. Shortliffe EH et al define the kinds of decision support systems by the roles they play in the decision making process. The authors state that any computer system that deals with clinical data or medical knowledge is intended to provide decision support. This article will discuss fact and fiction regarding decision support systems beginning with information systems that support the decision making process to more sophisticated knowledge based systems that provide interpretation and analysis of data. PMID- 8202069 TI - The hired gun expert witness. AB - This article briefly discusses the role of the expert physician witness at trial and describes what is emerging as the physician professional witness (AKA hired gun). The trial court's powers to evaluate the professionalism and objectivity of an expert witness are examined in light of a recent Western District Missouri Court of Appeals case. This case, while limited to its peculiar set of facts, permitted both a hearing and production of documents of a physician who had been hired to testify. This article reviews the role of the expert physician witness in Missouri litigation in light of recent caselaw outlining discovery procedures to monitor use of professional witnesses. The term "professional witness" does not refer to witnesses who are professionals, but rather to persons who make their entire living witnessing. The Missouri Court of Appeals ruling in State ex rel. Lichtor v. Clark, 845 S.W.2d (Mo.App. W.D. 1992) elucidates the Missouri Courts' authority in sorting out unprofessional physicians who would offer unobjective expert testimony. While this particular article is intended for medical readership and discusses expert physician witnesses, expert witnesses can come from any profession including engineering, accounting, nursing, etc. It might thus be assumed that the Lichtor Court's procedure may be applied to any expert whose objectivity has been put into question. PMID- 8202070 TI - Calvarial defect reconstruction. AB - The history of skull trepanation is almost as old as that of humanity. For thousands of years it has been performed for the treatment of numerous medical maladies. The Andean Incas, early Asians and South Seas Islanders, are amongst the many people to perform calvarial trepanation. Hippocrates described techniques for the use of the trepan in early Greek times. With the production of a skull opening comes the challenge of developing methods for closing the defect. It is in reality, more challenging to repair the defect than to create it. Man, with his never ending ingenuity, has tried to develop many techniques. We will discuss some of them and present our method of choice for closure of skull defects. PMID- 8202072 TI - Include physicians in reform decisions. PMID- 8202071 TI - The effect of physical activity on all cause mortality compared to cardiovascular mortality: a review of research and recommendations. AB - The American Heart Association states that sedentary lifestyle is a major risk factor for CVD comparable to hypercholesterolemia, hypertension, and cigarette smoking. Nearly 60% of Missourians are sedentary. This article reviews and summarizes recent literature on physical inactivity and mortality, makes recommendations to physicians regarding exercise and health benefits, and discusses the contributions physicians can make toward increasing physical activity levels in their patients. PMID- 8202073 TI - Laboratory management of agents associated with hantavirus pulmonary syndrome: interim biosafety guidelines. Centers for Disease Control and Prevention. AB - This report provides interim biosafety guidelines for preventing laboratory associated infections with agents that cause hantavirus pulmonary syndrome. The guidelines are based on extensive laboratory experience with the other hantaviruses--particularly work involving the use of permissive host animal species--and on the limited experience with a hantavirus recently isolated from deer mice. The guidelines address handling patient-derived specimens, propagating viruses in culture (including viral concentrate preparations), and housing and handling infected animals. These recommendations were developed with the assistance of expert consultants during a meeting of the American Society of Tropical Medicine and Hygiene, Subcommittee on Arbovirus Laboratory Safety, November 2, 1993, in Atlanta. PMID- 8202074 TI - Update: coccidioidomycosis--California, 1991-1993. AB - Coccidioidomycosis is an infection caused by the fungus Coccidioides immitis, which resides in the soil in some areas of Arizona, California, Nevada, New Mexico, Texas, and Utah. Infection can occur when airborne, infective arthroconidia are inhaled. Symptomatic coccidioidomycosis, which occurs in approximately 40% of all infections, has a wide clinical spectrum, including mild influenza-like illness, severe pneumonia, and disseminated disease. Beginning in 1991, the number of cases of coccidioidomycosis reported annually to the California Department of Health Services (CDHS) increased dramatically (1) (Figure 1). This report summarizes the occurrence of coccidioidomycosis in California during 1991-1993. PMID- 8202075 TI - Head injuries associated with motorcycle use--Wisconsin, 1991. AB - From 1989 through 1991, a total of 9913 persons in the United States died as a result of crashes while operating or riding motorcycles (1). Although use of motorcycle helmets is an effective means for preventing crash-related fatal injuries (2), 25 states and the District of Columbia have not yet enacted laws requiring the universal use of motorcycle helmets (1). This report describes a study by the University of Wisconsin and the Wisconsin Department of Transportation in which linked police reports and hospital discharge records for 1991 were used to assess the risk for head injury for motorcyclists in motor vehicle crashes, the initial inpatient hospital charges for motorcyclists with head injuries resulting from crashes, and the reduction in injuries and fatalities associated with universal helmet use. PMID- 8202076 TI - Arthritis prevalence and activity limitations--United States, 1990. AB - Arthritis is a leading cause of work-related disability and the leading cause of disability among persons aged > or = 65 years in the United States (1). However, there are few national or state-specific estimates and no projections of arthritis prevalence or its impact (2). To develop national and state estimates of arthritis prevalence and physical activity limitation for 1990 and to project these measures through 2020, rates derived from household interview data from the 1989-1991 National Health Interview Survey (NHIS) were applied to the 1990 census population and to census population projections. This report presents the results of that analysis. PMID- 8202077 TI - Knowledge and practices among injecting-drug users of bleach use for equipment disinfection--New York City, 1993. AB - Sharing (i.e., multiperson use) of drug-injection equipment among injecting-drug users (IDUs) is a major risk factor in the transmission of human immunodeficiency virus (HIV) and other bloodborne pathogens. Abstaining from injection of drugs eliminates this risk; disinfection of needles and syringes with household bleach can reduce this risk. Because studies suggest the effectiveness of bleach disinfection may be limited, the March 1993 National Institute on Drug Abuse (NIDA) Community Alert Bulletin included recommendations that IDUs who do not stop injecting and sharing injection equipment use full-strength household bleach and keep the bleach in contact with the equipment for at least 30 seconds (1). To determine whether these new recommendations had been disseminated effectively to IDUs, the knowledge of bleach use for disinfection of drug-injection equipment among IDUs participating in a NIDA-sponsored New York City cohort study was assessed during August-December 1993. This report presents data about knowledge of bleach use for disinfection among persons who reported injecting drugs at least once during the 3-6 months preceding the interview. PMID- 8202078 TI - Viral gastroenteritis associated with consumption of raw oysters--Florida, 1993. AB - During November 20-30, 1993, four county public health units (CPHUs) of the Florida Department of Health and Rehabilitative Services (HRS) in northwestern Florida conducted preliminary investigations of seven separate outbreaks of foodborne illness following consumption of raw oysters. On December 1, the HRS State Health Office initiated an investigation to characterize the illness, examine risk factors for oyster-associated gastroenteritis, and quantify the dose response relation. This report presents the findings of these two investigations. PMID- 8202079 TI - NIOSH alert: request for assistance in preventing drownings of commercial fishermen. PMID- 8202080 TI - Open reading frames in the antisense strands of genes coding for glycolytic enzymes in Saccharomyces cerevisiae. AB - Open reading frames longer than 300 bases were observed in the antisense strands of the genes coding for the glycolytic enzymes phosphoglucose isomerase, phosphoglycerate mutase, pyruvate kinase and alcohol dehydrogenase I. The open reading frames on both strands are in codon register. It has been suggested that proteins coded in codon register by complementary DNA strands can bind to each other. Consequently, it was interesting to investigate whether the open reading frames in the antisense strands of glycolytic enzyme genes are functional. We used oligonucleotide-directed mutagenesis of the PGI1 phosphoglucose isomerase gene to introduce pairs of closely spaced base substitutions that resulted in stop codons in one strand and only silent replacements in the other. Introduction of the two stop codons into the PGI1 sense strand caused the same physiological defects as already observed for pgil deletion mutants. No detectable effects were caused by the two stop codons in the antisense strand. A deletion that removed a section from -31 bp to +109 bp of the PGI1 gene but left 83 bases of the 3' region beyond the antisense open reading frame had the same phenotype as a deletion removing both reading frames. A similar pair of deletions of the PYK1 gene and its antisense reading frame showed identical defects. Our own Northern experiments and those reported by other authors using double-stranded probes detected only one transcript for each gene. These observations indicate that the antisense reading frames are not functional. On the other hand, evidence is provided to show that the rather long reading frames in the antisense strands of these glycolytic enzyme genes could arise from the strongly selective codon usage in highly expressed yeast genes, which reduces the frequency of stop codons in the antisense strand. PMID- 8202081 TI - Evolutionary divergence of human chromosome 9 as revealed by the position of the ABL protooncogene in higher primates. AB - Attempts to solve the fundamental questions regarding the descent of man are dogged by superstitions and unexamined orthodoxies. The origin of humans, established a decade ago based upon cytological analysis of ape chromosomes, continues to be called into question. Although molecular methods have provided a framework for tracing the paths of human evolution, conclusive evidence remains elusive. We have used a single ABL gene probe derived from human chromosome 9 to assess the direction of change in the equivalent ape chromosomes. This approach has resulted in a few surprises which again challenge the prevailing view of early primate evolution based solely on chromosome banding patterns. The ABL proto-oncogene is present on human chromosome 9 at band q34. Similar DNA sequences presumed to represent an ABL gene, are present on chromosome 11 in chimpanzee (Pan troglodytes) but at a different relative location, indicating that the mechanism of the origin of human chromosome 9 is far more complex than has previously been suggested. Nevertheless, in gorilla (Gorilla gorilla) and orangutan (Pongo pygmaeus), the equivalent to human chromosome band 9 q34 is apparently located on chromosome 13 at a putative telomeric position and no discernible differences could be established. Despite the presence of the ABL protooncogene on human equivalent ape chromosomes, molecular systematics will continue to generate enigmas in the evolutionary context until the entire genome is sequenced. PMID- 8202082 TI - Regulation of replication of plasmid pBR322 in amino acid-starved Escherichia coli strains. AB - The stringent response causes inhibition of replication of plasmid pBR322 in amino acid-starved Escherichia coli cells whereas in relaxed mutants the replication of this plasmid proceeds for several hours. On the basis of density shift experiments and pulse-labelling experiments we showed that most of the pBR322 molecules begin replication during the relaxed response and the rate of plasmid DNA synthesis in unstarved and isoleucine-starved relA- bacteria is similar. We found that the Rom function plays a key role in the stringent control of plasmid pBR322 replication, as insertional inactivation of the rom gene causes amplification of pBR322rom- in both relA- and relA+ strains during amino acid starvation. Moreover, pUC19, which is a pBR322-derived plasmid lacking the rom gene, behaves like pBR322rom-, whereas introduction of the rom gene into the pUC19 replicon drives it into the pBR322 mode of replication in amino acid starved bacteria. A model for the regulation of pBR322 plasmid DNA replication by Rom protein in amino acid-starved Escherichia coli strains is proposed. PMID- 8202083 TI - Requirement of the Pro-Cys-His-Arg sequence for O6-methylguanine-DNA methyltransferase activity revealed by saturation mutagenesis with negative and positive screening. AB - O6-Methylguanine-DNA methyltransferase catalyzes transfer of a methyl group from O6-methylguanine and O4-methylthymine of DNA to a cysteine residue of the enzyme protein, thereby repairing the mutagenic and carcinogenic lesions in a single step reaction. There are highly conserved amino acid sequences around the methyl accepting cysteine site in eleven molecular species of methyltransferases. To elucidate the significance of the conserved sequence, amino acid substitutions were introduced by site-directed mutagenesis of the cloned DNA for Escherichia coli Ogt methyltransferase, and the activity and stability of mutant forms of the enzyme were examined. When cysteine-139, to which methyl transfer occurs, was replaced by other amino acids, all of the mutants showed the methyltransferase negative phenotype. Methyltransferase-positive revertants, isolated from one of the negative mutants, had restored codons for cysteine. Thus the cysteine residue is essential for acceptance of the methyl group and is not replaceable by other amino acids. Using this negative and positive selection procedure, the analysis was extended to other residues near the acceptor site. At the histidine-140 and arginine-141 sites, all the positive revertants isolated carried codons for amino acids identical to those of the wild-type protein. At proline-138, five substitutions (serine, glutamine, threonine, histidine, and alanine) exhibited the positive phenotype but levels of methyltransferase activity in extracts of cells harboring these mutant forms were very low. This suggests that the proline residue at this site is important for maintaining the proper conformation of the protein. With valine-142 substitutions there were seven types of positive revertants, among which mutants carrying isoleucine, cysteine, leucine, and alanine showed relatively high levels of methyltransferase activity. These results indicate that the sequence Pro-Cys-His-Arg is a sine qua non for methyltransferase to exert its function. PMID- 8202084 TI - Epigenetic variants of a transgenic petunia line show hypermethylation in transgene DNA: an indication for specific recognition of foreign DNA in transgenic plants. AB - We analysed de novo DNA methylation occurring in plants obtained from the transgenic petunia line R101-17. This line contains one copy of the maize A1 gene that leads to the production of brick-red pelargonidin pigment in the flowers. Due to its integration into an unmethylated genomic region the A1 transgene is hypomethylated and transcriptionally active. Several epigenetic variants of line 17 were selected that exhibit characteristic and somatically stable pigmentation patterns, displaying fully coloured, marbled or colourless flowers. Analysis of the DNA methylation patterns revealed that the decrease in pigmentation among the epigenetic variants was correlated with an increase in methylation, specifically of the transgene DNA. No change in methylation of the hypomethylated integration region could be detected. A similar increase in methylation, specifically in the transgene region, was also observed among progeny of R101-17del, a deletion derivative of R101-17 that no longer produces pelargonidin pigments due to a deletion in the A1 coding region. Again de novo methylation is specifically directed to the transgene, while the hypomethylated character of neighbouring regions is not affected. Possible mechanisms for transgene-specific methylation and its consequences for long-term use of transgenic material are discussed. PMID- 8202085 TI - ADP-glucose pyrophosphorylase in shrunken-2 and brittle-2 mutants of maize. AB - The Shrunken-2 (Sh2) and Brittle-2 (Bt2) genes of maize encode subunits of the tetrameric maize endosperm ADPglucose pyrophosphorylase. However, in all sh2 and bt2 mutants so far examined, measurable ADPglucose pyrophosphorylase activity remains. We have investigated the origin of the residual activity found in various sh2 and bt2 mutants as well as tissue specific expression and post translational modification of the Sh2 and Bt2 proteins. Sh2 and Bt2 cDNAs were expressed in Escherichia coli and antibodies were prepared against the resulting proteins SH2 and BT2 specific antibodies were used to demonstrate that SH2 and BT2 are endosperm specific, are altered or missing in various sh2 or bt2 mutants, and have a mol. wt. of 54 and 51 kDa respectively in the wild type. The Sh2 and Bt2 transcripts are also endosperm specific. Ten sh2 and eight bt2 mutants show varying severity of phenotypes expressed at transcript, protein subunit and kernel level. Synthesis of multiple transcripts and proteins commonly occurs as a result of sh2 or bt2 mutation. While all mutants produce detectable enzymic activity, not all produce detectable transcripts and proteins. To examine the origin of the apparent non-SH2/BT2 endosperm enzymic activity, homologs of Sh2 and Bt2, designated Agp1 and Agp2 respectively, were isolated from an embryo cDNA library and found to hybridize to endosperm transcripts distinct from those of Sh2 and Bt2. Thus Agp1 and Agp2 or closely related genes may be responsible for the residual activity in some sh2 and bt2 mutants. Surprisingly, no evidence of post-translational modification of the SH2 and BT2 protein subunits was detected. PMID- 8202086 TI - The catalytic domain of Escherichia coli K-12 adenylate cyclase as revealed by deletion analysis of the cya gene. AB - In Escherichia coli, adenylate cyclase activity is regulated by phosphorylated EnzymeIIA(Glc), a component of the phosphotransferase system for glucose transport. In strains deficient in EnzymeIIA(Glc), cAMP levels are very low. Adenylate cyclase containing the D414N substitution produces a low level of cAMP and it has been proposed that D414 may be involved in the process leading to activation by EnzymeIIA(Glc). In this work, spontaneous secondary mutants producing large amounts of cAMP in strains deficient in EnzymeIIA(Glc) were obtained. The secondary mutations were all deletions located in the cya gene around the D414N mutation, generating adenylate cyclases truncated at the carboxyl end. Among them, a 48 kDa protein (half the size of wild-type adenylate cyclase) was shown to produce ten times more cAMP than wild-type adenylate cyclase in strains deficient in EnzymeIIA(Glc). In addition, this protein was not regulated in strains grown on glucose and diauxic growth was abolished. This allowed the definition of a catalytic domain that is not regulated by the phosphotransferase system and produces levels of cAMP similar to that of regulated wild-type adenylate cyclase in wild-type strains grown in the absence of glucose. Further analysis allowed the characterization of the COOH-terminal regulatory domain, which is proposed to be inhibitory to the activity of the catalytic domain. PMID- 8202087 TI - HIV-1 integrase blocks infection of bacteria by single-stranded DNA and RNA bacteriophages. AB - Expression of human immunodeficiency virus-1 integrase in Escherichia coli, at levels that had no effect on bacterial cell growth, blocked plaque formation by bacteriophages having single-stranded genomic DNA (M13) or RNA (R17, Q beta, PRR1). Plaque formation by phages having double-stranded genomic DNA (T4, PR4) was unaffected. Integrase also inhibited infection by the phagemid M13KO7, but it had no effect on production of phage once infection by M13KO7 was established. This result indicated that integrase affects an early stage in infection. Integrase also inhibited phage production following transfection by either single stranded or double-stranded (replicative form) M13 DNA, it blocked M13 DNA replication, as assayed by incorporation of radioactive nucleotides into DNA, and it failed to affect bacterial pilus function. These data suggest that integrase interacts in vivo with phage nucleic acid, a conclusion supported by studies in which integrase was shown to have a DNA-binding activity in its C-terminal portion. This portion of integrase was both necessary and sufficient for interference of plaque formation by M13 in the present study. Expression of the N terminal portion of integrase at the same level as intact integrase had little effect on phage growth, indicating that expression of foreign protein in general was not responsible for the inhibitory effect. The simple bacteriophage assay described is potentially useful for identifying integrase mutants that lack single-stranded DNA binding activity. PMID- 8202088 TI - Ds read-out transcription in transgenic tomato plants. AB - To select for Ds transposition in transgenic tomato plants a phenotypic excision assay, based on restoration of hygromycin phosphotransferase (HPT II) gene expression, was employed. Some tomato plants, however, expressed the marker gene even though the Ds had not excised. Read-out transcriptional activity of the Ds element is responsible for the expression of the HPT II gene. Transcription initiation was mapped to multiple positions spanning about 300 bp in the subterminal part of the Ds element. In this respect Ds in tomato resembles the maize element Mu1, which also promotes transcription outward from the element. Transposon read-out transcription might thus supply an additional general mechanism for controlling plant gene expression. PMID- 8202089 TI - Plant ribosomal DNA external spacer binding factors: a novel protein binds specifically to a sequence close to the primary pre-rRNA processing site. AB - Sequence analyses of the ribosomal DNA (rDNA) external spacer region revealed a peculiar structure around the primary pre-rRNA processing site in radish. Using the electrophoretic mobility shift assay, DNAse I footprinting and methylation interference analysis, we have identified in radish extracts a novel nuclear factor, NF B, that recognises this region. NF B binds to a unique CGATTTTGCCCCTGA sequence located 164 bp downstream of the transcription initiation site and immediately upstream of the pre-rRNA processing site. Interestingly, this motif is flanked by four homologous sequences, including the primary pre-rRNA processing site, which are not recognised by NF B. Based on these data and the prediction that alternative hairpin loops can be formed in this region of the nascent pre-rRNA, a putative role for NF B as a factor coupling transcription and pre-rRNA processing is discussed. NF B is unique among plant and animal rDNA binding proteins and it differs from a previously described radish factor and from other proteins that bind to plant rDNA promoters. PMID- 8202090 TI - Molecular cloning and sequence analysis of an Azospirillum brasilense indole-3 pyruvate decarboxylase gene. AB - Azospirillum brasilense isolated from the rhizosphere of different plants has the ability to excrete indole-3-acetic acid (IAA) into the culture media. Cosmid p0.2, isolated from an A. brasilense Sp245 genome library in pLAFR1, complements the Tn5-induced mutant SpM7918 of A. brasilense Sp6 which excretes reduced amounts of IAA. Restriction mapping and gene expression studies identified a BglII-EcoRI 4.3 kb fragment of p0.2 sufficient for the restoration of high levels of IAA production in mutant SpM7918. Tn5 mutagenesis localized the gene responsible on a 1.8 kb SmaI fragment. Nucleotide sequence analysis revealed that this fragment contains one complete open reading frame. The predicted protein sequence shows extensive homology with the indole-3-pyruvate decarboxylase of Enterobacter cloacae and the pyruvate decarboxylases of Saccharomyces cerevisiae and Zymomonas mobilis. The A. brasilense mutant Sp245a, constructed by homogenotization of a Tn5 insertion derivative of the 1.8 kb SmaI fragment, also displayed reduced IAA production. Introduction of the cloned wild-type gene into Rhizobium meliloti 1021 resulted in increased IAA production. Cell-free extracts prepared from R. meliloti and A. brasilense transconjugants harboring this gene could convert indole-3-pyruvic acid to indole-3-acetaldehyde and tryptophol. These results clearly demonstrate that IAA production in A. brasilense is mediated by indole-3-pyruvate decarboxylase. PMID- 8202091 TI - The mitochondrial genome of yeast Hansenula wingei encodes NADH dehydrogenase subunit genes ND4L and ND5. AB - Genes homologous to those encoding mitochondrial NADH dehydrogenase subunits ND4L and ND5 in filamentous fungi were identified in the mitochondrial genome of a budding yeast, Hansenula wingei. The structure and expression of these genes were investigated. The H. wingei ND4L gene is 282 bp long, and potentially codes for a polypeptide of 94 amino acids. The putative ND4L protein sequence shares about 46% homology with the analogous mitochondrial proteins of filamentous fungi. The H. wingei ND5 gene is 1935 bp long, and encodes a 645-residue polypeptide. The derived ND5 protein shares about 38% sequence homology with the analogue in filamentous fungi. The ND4L and ND5 genes have no intervening sequence, and form a gene cluster in the order of 5'-ND4L-ND5-3'. A presumptive mature dicistronic or polycistronic transcript of these genes was detected by Northern blot hybridization. These results strongly indicate that these ND4L and ND5 genes are active. As far as we are aware, this is the first report on the identification of mitochondrially encoded ND genes in yeast. PMID- 8202092 TI - Mapping of transcriptional start sites of the cea and cei genes of the ColE7 operon. AB - Two transcriptional start sites were identified 77 and 78 nucleotides upstream of the translation initiation codon of the colicin E7 gene (ceaE7). The guanosine nucleotide located at the fifth position of the SOS box is probably a universal transcriptional start site of all E group colicins. Major and minor transcripts of the immunity gene (cei) are initiated at the 3' end of the cea gene. Relative to the -10 sequence, CAAAAT, of the major ceiE7 promoter, the corresponding region of the cei gene of other E group colicins has an increased content of guanosine nucleotides. However the -10 sequence of the minor ceiE7 promoter, TATGAT, was found to be conserved in other colicin promoters. The results indicate that the structure of the major promoter of the ceiE7 gene is unique among the E group colicins. PMID- 8202093 TI - Cloning and characterization of a secY homolog from Chlamydia trachomatis. AB - Characterization of the genes involved in the process of protein translocation is important in understanding their structure-function relationships. However, little is known about the signals that govern chlamydial gene expression and translocation. We have cloned a 1.7 kb HindIII-PstI fragment containing the secY gene of Chlamydia trachomatis. The complete nucleotide sequence reveals three open reading frames. The amino acid sequence shows highest homology with Escherichia coli proteins L15, SecY and S13, corresponding to the spc-alpha ribosomal protein operons. The product of the C. trachomatis secY gene is composed of 457 amino acids with a calculated molecular mass of 50,195 Daltons. Its amino acid sequence shows 27.4% and 35.7% identity to E. coli and Bacillus subtilis SecY proteins, respectively. The distribution of hydrophobic amino acids in the C. trachomatis secY gene product is suggestive of it being an integral membrane protein with ten transmembrane segments, the second, third and seventh membrane segments sharing > 45% identity with E. coli SecY. Our results suggest that despite evolutionary differences, eubacteria share a similar protein export apparatus. PMID- 8202094 TI - A population-based study of the risk of recurrence of birth defects. AB - BACKGROUND: Certain birth defects are known to recur in families, but most estimates of the risk of recurrence have come from clinic-based studies. In this study we estimated the risk of recurrent birth defects using a population-based registry. METHODS: The study was based on the records of the first and second infants delivered by 371,933 women from 1967 through 1989. The records are maintained by the Medical Birth Registry of Norway. For the 9192 women whose first infant had a birth defect, we determined the relative risk of similar and dissimilar defects in the second infant. The reference population was women whose first infant had no defect. RESULTS: Among first infants, 2.5 percent had a birth defect. The mothers of affected first infants were 2.4 times as likely as other women to have second infants with any registered defect. This increased risk was due primarily to an increased (7.6 times higher) risk of the same defect in the second infant as in the first (95 percent confidence interval, 6.5 to 8.8) and secondarily to a slightly increased (1.5 times higher) risk of a different defect in the second infant (95 percent confidence interval, 1.3 to 1.7). Among the women who lived in the same municipality during both pregnancies, the relative risk of having a second infant with the same defect was 11.6, as compared with 5.1 among the women who moved to another municipality after the birth of their first infant (P < 0.001). CONCLUSIONS: Among women whose first infant has a birth defect, the risk of the same defect in the second infant is substantially increased and the risk of a different defect in the second infant is slightly increased. Environment plays a strong part in repeated defects. PMID- 8202095 TI - Long-term risk of breast cancer in women with fibroadenoma. AB - BACKGROUND: Fibroadenomas are benign breast tumors that are commonly diagnosed in young women and are associated with a slight increase in the risk of breast cancer. These lesions vary considerably in their histologic characteristics. We assessed the correlation between the histologic features of fibroadenomas and the risk of subsequent breast cancer. METHODS: We conducted a retrospective cohort study of a consecutive series of patients with fibroadenoma diagnosed between 1950 and 1968. Follow-up data were obtained for 1835 patients (90 percent of those eligible). Fibroadenomas with cysts, sclerosing adenosis, epithelial calcifications, or papillary apocrine changes were classified as complex. The rate of subsequent breast cancer among the patients was compared with the rates in two control groups, women listed in the Connecticut Tumor Registry and women chosen from among the patients' sisters-in-law. RESULTS: The risk of invasive breast cancer was 2.17 times higher among the patients with fibroadenoma than among the controls (95 percent confidence interval, 1.5 to 3.2). The relative risk increased to 3.10 among patients with complex fibroadenomas (95 percent confidence interval, 1.9 to 5.1) and remained elevated for decades after diagnosis. Patients with benign proliferative disease in the parenchyma adjacent to the fibroadenoma had a relative risk of 3.88 (95 percent confidence interval, 2.1 to 7.3). Patients with a family history of breast cancer in whom complex fibroadenoma was diagnosed had a relative risk of 3.72, as compared with controls with a family history (95 percent confidence interval, 1.4 to 10). Two thirds of the patients had noncomplex fibroadenomas and no family history of breast cancer and did not have an increased risk. CONCLUSIONS: Fibroadenoma is a long-term risk factor for breast cancer. The risk is increased in women with complex fibroadenomas, proliferative disease, or a family history of breast cancer. PMID- 8202096 TI - The 1993 epidemic of pertussis in Cincinnati. Resurgence of disease in a highly immunized population of children. AB - BACKGROUND: In 1993 there was a resurgence of pertussis in the United States. Altogether, 6335 cases were reported, the most in 26 years. METHODS: Using active microbiologic surveillance, we investigated the epidemic of pertussis in Greater Cincinnati in 1993. The population of 1.7 million in this area is served by a single children's hospital and pertussis laboratory. We prospectively followed patients given a new diagnosis of pertussis in July through September 1993 to determine the characteristics of the epidemic. RESULTS: From 1979 to 1992, there was a cumulative total of 542 cases of pertussis. In 1993, 352 cases were diagnosed, an increase of 259 percent over the 1992 total. Sixty-three percent of the cases had positive cultures for Bordetella pertussis, 18 percent were positive on direct fluorescent-antibody testing only, and 19 percent were diagnosed clinically. The outbreak began in the suburbs during the summer and spread through Greater Cincinnati. Of 255 total cases diagnosed in July through September (195 excess cases over the maximal base-line level of 20 per month in the previous 14 years), 75 percent were in white patients and 67 percent of the patients had private insurance or paid for care out of pocket. In 1993, as compared with 1979 through 1992, there was a shift in incidence from younger infants to older children; the percentages of cases according to age group were as follows: 0 to 6 months, 53 percent from 1979 through 1992 and 35 percent in 1993 (P < 0.001); 7 months to 5 years, 33 percent and 43 percent (P < 0.002); 6 to 12 years, 5 percent and 11 percent (P < 0.001); and more than 12 years, 5 percent and 11 percent (P < 0.003). Immunization records revealed that 74 percent (75 of 101) of the children with pertussis who were 19 months to 12 years old had received four or five doses of the combined diphtheria-pertussis-tetanus (DPT) vaccine, and that 82 percent (103 of 126) of those 7 to 71 months old had received at least three doses of DPT vaccine. The whole-cell vaccines used came from both of the major manufacturers (Connaught Laboratories and Lederle Laboratories). Disease was not severe, but 80 of the 255 children (31 percent) given diagnoses during the three epidemic months were hospitalized. There were no deaths. CONCLUSIONS: Since the 1993 pertussis epidemic in Cincinnati occurred primarily among children who had been appropriately immunized, it is clear that the whole-cell pertussis vaccine failed to give full protection against the disease. PMID- 8202097 TI - Brief report: malaria probably locally acquired in New Jersey. PMID- 8202098 TI - Images in clinical medicine. Loffler's endocarditis. PMID- 8202099 TI - Pulmonary-function testing. PMID- 8202100 TI - Sotalol. AB - Sotalol is a novel antiarrhythmic agent combining beta-adrenergic-antagonist actions with the ability to increase cardiac repolarization and refractoriness. The drug's electrophysiologic and clinical profile is different from that of conventional beta-receptor antagonists. As compared with other antiarrhythmic agents, sotalol prevents recurrences of arrhythmia in a higher proportion of patients, particularly among those presenting with ventricular tachycardia and aborted sudden cardiac death. The net hemodynamic effect of sotalol is the result of a balance between the depressant effects due to beta-receptor blockade and an action that tends to increase contractility. Although initially marketed in the United States for treatment of life-threatening ventricular arrhythmias, sotalol also has demonstrated efficacy in many patients with supraventricular arrhythmias. As with all drugs that prolong the QT interval, the syndrome of torsade de pointes is a serious potential adverse effect. PMID- 8202101 TI - DNA and the genetic code. PMID- 8202102 TI - Clinical problem-solving. Stopping short of certainty. PMID- 8202103 TI - A new series on molecular medicine for clinicians. PMID- 8202104 TI - Finding the causes of birth defects. PMID- 8202105 TI - Cancer therapy meets p53. PMID- 8202106 TI - Transient increase in the risk of breast cancer after giving birth. AB - BACKGROUND: The effect of pregnancy on the risk of breast cancer is not clear. We tested the hypothesis that the risk of breast cancer increases transiently after pregnancy but then falls to a level below that of age-matched nulliparous women. METHODS: We conducted a case-control study of a nationwide cohort in Sweden, using a computerized record linkage between the Cancer Registry and the Fertility Registry. The study subjects were women born from 1925 through 1960 who were resident citizens of Sweden at the time of the 1960 census. A total of 12,666 patients with breast cancer were compared with 62,121 age-matched control subjects. We used conditional logistic regression to estimate odds ratios for the development of breast cancer at different ages, according to maternal age at first delivery (in uniparous as compared with nulliparous women) and age at second delivery (in biparous as compared with uniparous women). RESULTS: Uniparous women were at higher risk of breast cancer than nulliparous women for up to 15 years after childbirth and at lower risk thereafter. The excess risk was most pronounced among women who were older at the time of their first delivery (odds ratio 5 years after delivery among women 35 years old at first delivery, 1.26; 95 percent confidence interval, 1.10 to 1.44). Women who had two pregnancies had a less striking increase in risk. CONCLUSIONS: Pregnancy has a dual effect on the risk of breast cancer: it transiently increases the risk after childbirth but reduces the risk in later years. In women with two pregnancies, the short-term adverse effect is masked by the long-term protection imparted by the first pregnancy. A plausible biologic interpretation is that pregnancy increases the short-term risk of breast cancer by stimulating the growth of cells that have undergone the early stages of malignant transformation but that it confers long-term protection by inducing the differentiation of normal mammary stem cells that have the potential for neoplastic change. PMID- 8202107 TI - Gastrointestinal bleeding in critically ill patients. PMID- 8202108 TI - Gastrointestinal bleeding in critically ill patients. PMID- 8202109 TI - Gastrointestinal bleeding in critically ill patients. PMID- 8202110 TI - Ranitidine and recurrent hemorrhage from duodenal ulcer. PMID- 8202111 TI - Laparoscopic cholecystectomy. PMID- 8202112 TI - Laparoscopic surgery. PMID- 8202113 TI - A simpler technique for umbilical-cord blockade of an acardiac twin. PMID- 8202114 TI - Central anticholinergic syndrome with the antimalarial drug mefloquine. PMID- 8202115 TI - Aplastic anemia after exposure to burning oil. PMID- 8202116 TI - Dipyridamole for renal phosphate leak? PMID- 8202117 TI - More on acyclovir for chickenpox. PMID- 8202118 TI - The struggle between managed care and fee-for-service practice. PMID- 8202119 TI - Charitable research. AB - British charities will not, after all, have to vouch for the quality of what their dependent researchers publish. PMID- 8202120 TI - Concern over 'invisible problem' of HIV blood in developing countries. PMID- 8202121 TI - . . . as NIH tightens up on academic-industry deals. PMID- 8202122 TI - Doubts greet violence-research funding plea. PMID- 8202123 TI - War of words over future of Berlin teaching hospitals. PMID- 8202124 TI - Energy and biotechnology top Euro-Parliament's agenda. PMID- 8202125 TI - US health agencies at odds over trial deaths. PMID- 8202126 TI - Critic still lays blame for AIDS on lifestyle, not HIV. PMID- 8202127 TI - Clinical analysis in Egypt. PMID- 8202128 TI - Gene safety. PMID- 8202129 TI - Cell-cycle regulation by numbers. PMID- 8202130 TI - Glycoprotein hormones. A clasped embrace. PMID- 8202131 TI - Immunology. NF-AT comes under control. PMID- 8202132 TI - Neurobiology. A new job for the thalamus. PMID- 8202133 TI - Single sweetness signal. PMID- 8202134 TI - Scaling and brain connectivity. PMID- 8202135 TI - Regional variation in fruitflies. PMID- 8202136 TI - Crystal structure of human chorionic gonadotropin. AB - The three-dimensional structure of human chorionic gonadotropin shows that each of its two different subunits has a similar topology, with three disulphide bonds forming a cystine knot. This same folding motif is found in some protein growth factors. The heterodimer is stabilized by a segment of the beta-subunit which wraps around the alpha-subunit and is covalently linked like a seat belt by the disulphide Cys 26-Cys 110. This extraordinary feature appears to be essential not only for the association of these heterodimers but also for receptor binding by the glycoprotein hormones. PMID- 8202137 TI - Feature-linked synchronization of thalamic relay cell firing induced by feedback from the visual cortex. AB - The function of the massive feedback projection from visual cortex to its thalamic relay nucleus has so far eluded any clear overview. This feedback exerts a range of effects, including an increase in the inhibition elicited by moving contours, but the functional logic of the direct connections to the thalamic cells that relay the retinal input to the cortex remains largely unknown. In contrast to its thalamic nucleus, the visual cortex is characterized by cells that are strongly sensitive to the orientation of moving contours. Here we report that when driven by moving oriented visual stimuli the cortical feedback induces correlated firing in relay cells. This cortically induced correlation of relay cell activity produces coherent firing in those groups of relay cells with receptive field alignments appropriate to signalling the particular orientation of the moving contour to the cortex. Synchronization of relay cell firing means that they will elicit temporally overlapping excitatory postsynaptic potentials in their cortical target cells, thus increasing the chance that the cortical cells will fire. Effectively this increases the gain of the input for feature linked events detected by the cortex. We propose that this feedback loop serves to lock or focus the appropriate circuitry onto the stimulus feature. PMID- 8202138 TI - NMDA receptors and activity-dependent tuning of the receptive fields of spinal cord neurons. AB - After peripheral nerve section, sensory neurons regenerate but do not regain their original topographical position in the skin. Here we report that in the early stages of sciatic nerve regeneration, the cutaneous receptive fields (RFs) of dorsal horn neurons are larger than normal, reflecting the disorganized topography of the regenerated afferents. When nerve regeneration is complete, small contiguous RFs emerge, indicating a central compensation for the disrupted peripheral somatotopy. If the NMDA receptor antagonist MK801 is given during regeneration, RFs do not show this reorganization, but remain large and diffuse. We suggest that the coincident activity of afferents, newly innervating adjacent or overlapping cutaneous territory, acts through postsynaptic NMDA receptors to strengthen the central effectiveness of these inputs at the expense of other non adjacent and non-coincidently activated inputs. In this way, dorsal horn neurons may attain and retain restricted RFs in the face of a spatially dispersed afferent input. PMID- 8202139 TI - Altered microtubule organization in small-calibre axons of mice lacking tau protein. AB - The tau gene encodes a protein (Tau) that is a major neuronal microtubule associated protein localized mostly in axons. It has microtubule-binding and tubulin-polymerizing activity in vitro and is thought to make short crossbridges between axonal microtubules. Further, tau-transfected non-neuronal cells extend long axon-like processes in which microtubule bundles resembling those in axons are formed. In contrast, tau antisense oligonucleotides selectively suppress axonal elongation in cultured neurons. Thus tau is thought to be essential for neuronal cell morphogenesis, especially axonal elongation and maintenance. To test this hypothesis, we used gene targeting to produce mice lacking the tau gene. We show that the nervous system of tau-deficient mice appears to be normal immunohistologically. Furthermore, axonal elongation is not affected in cultured neurons. But in some small-calibre axons, microtubule stability is decreased and microtubule organization is significantly changed. We observed an increase in microtubule-associated protein 1A which may compensate for the functions of tau in large-calibre axons. Our results argue against the suggested role of tau in axonal elongation but confirm that it is crucial in the stabilization and organization of axonal microtubules in a certain type of axon. PMID- 8202140 TI - A universal nucleoside for use at ambiguous sites in DNA primers. AB - A non-discriminatory base analogue, or universal base, would be an invaluable component of oligonucleotide probes and primers for solving the design problems that arise as a result of the degeneracy of the genetic code, or when only fragmentary peptide sequence data are available. We have designed an alternative to previous universal nucleoside candidates, a new analogue, 1-(2'-deoxy-beta-D ribofuranosyl)-3-nitropyrrole (designated M; Fig. 1), which maximizes stacking while minimizing hydrogen-bonding interactions without sterically disrupting a DNA duplex. Oligonucleotides containing M at several sites were used as primers for sequencing and the polymerase chain reaction. The sequencing primer d(5'-CGT AAM CAM AAM ACM AT-3') is as effective as the exact match d(5'-CGT AAT CAG AAA ACA AT-3'). It is also possible to sequence using a primer containing M at several contiguous positions, for example d(5'-CGT AAT MMM MMM MMM AT-3'). Melting curves show that duplexes formed on hybridization of the sequences d(5' CCT TTT TMT TTT TGG-3') and d(5'-CCA AAA AXA AAA AGG-3'), where X is A, C, G or T, melted at a lower temperature than the corresponding duplexes containing only d(A.T) and d(C.G) base pairs, but showing little variation among different X bases (Tm range 3 degrees C). PMID- 8202142 TI - . . . and in Britain also. PMID- 8202141 TI - NF-AT components define a family of transcription factors targeted in T-cell activation. AB - The NF-AT transcription complex is required for the expression of a group of proteins that collectively coordinate the immune response. Here we purify two proteins encoded by separate genes that represent the pre-existing (p) and cytosolic (c) components of NF-AT. Expression of the full-length complementary DNA encoding NF-ATc activates the interleukin (IL-2) promoter in non-T lymphocytes, whereas a dominant negative of NF-ATc specifically blocks activation of the IL-2 promoter in T lymphocytes, indicating that NF-ATc is required for IL 2 gene expression. NF-ATc RNA expression is largely restricted to lymphoid tissues and is induced upon T-cell activation. The other protein, NF-ATp, is highly homologous to NF-ATc over a limited domain which shows similarity to the Dorsal/Rel family, but has a wider tissue distribution. Agents that increase intracellular Ca2+ or activate protein kinase C independently modify NF-ATc, indicating that distinct signalling pathways converge on NF-ATc to regulate its function. PMID- 8202143 TI - US health reform falters. PMID- 8202144 TI - 'Misconduct' definitions still prove elusive. PMID- 8202145 TI - Biomedical levy gathers pace in US. PMID- 8202146 TI - Tensions grow over health research proposals. PMID- 8202147 TI - Breast cancer prevention trials 'can re-start'. PMID- 8202148 TI - Why use BST? PMID- 8202149 TI - Cocktail party effect made tolerable. PMID- 8202150 TI - Blood. Thrombopoietin--at last. PMID- 8202151 TI - Transcription. The essential twist. PMID- 8202152 TI - Origin of introns--early or late? PMID- 8202153 TI - Origin of introns--early or late. PMID- 8202154 TI - Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. AB - Physiological platelet synthesis is thought to require the humoral activities of meg-CSF and thrombopoietin, which respectively promote proliferation and maturation of megakaryocytic cells. A meg-CSF/thrombopoietin-like protein that is present in plasma of irradiated pigs has been purified and cloned. This protein binds to and activates the c-mpl protein, a member of the cytokine receptor superfamily. The isolated Mpl ligand shares homology with erythropoietin and stimulates both megakaryocytopoiesis and thrombopoiesis. PMID- 8202155 TI - Bilateral hand representation in the postcentral somatosensory cortex. AB - In accordance with its important role in prehensile activity, a large cortical area is devoted to representation of the digits. Within this large cortical zone in the macaque somatosensory cortex, the complexity of neuronal receptive field characteristics increases from area 3b to areas 1 and 2 (refs 1-7). This increase in complexity continues into the upper bank of the intraparietal sulcus, where the somatosensory cortex adjoins the parietal association cortex. In this bank, callosal connections are much denser than in the more anterior part of this cortical zone. We have now discovered a substantial number of neurons with receptive fields on the bilateral hands. It was previously thought that neuronal receptive fields were restricted to the contralateral side in this cortical zone. Neurons with bilateral receptive fields were not found after lesioning the postcentral gyrus in the contralateral hemisphere. The majority of these neurons had receptive fields of the most complex types, representing multiple digits, indicating that the interhemispheric transfer of information occurs at higher levels of the hierarchical processing in each hemisphere. PMID- 8202156 TI - Transport of cytoplasmic particles catalysed by an unconventional myosin in living Drosophila embryos. AB - Myosins are actin-activated ATPases that are able to translocate along actin filaments using energy derived from ATP hydrolysis. Non-muscle cells contain conventional myosins, which are similar in sequence and structure to muscle myosin, and a number of unconventional myosins whose head sequences are similar but tail sequences are unrelated to conventional myosins. The myosin superfamily currently consists of nine classes; Drosophila 95F is an unconventional myosin and the original member of class VI, which includes a homologue found in pig kidney. Some unconventional myosins have been suggested as mediators of some types of intracellular transport, but there is little direct evidence for this function (but see ref. 6). We have observed transport of cytoplasmic particles in live Drosophila embryos in three dimensions using computational optical sectioning microscopy. We present here evidence that this transport is actin based, ATP-dependent and catalysed by one such unconventional myosin, the 95F myosin. This is, to our knowledge, the first direct observation of transport catalysed by an unconventional myosin in living cells. PMID- 8202157 TI - Cloned Ca(2+)-dependent K+ channel modulated by a functionally associated protein kinase. AB - Calcium-dependent potassium (KCa) channels carry ionic currents that regulate important cellular functions. Like some other ion channels, KCa channels are modulated by protein phosphorylation. The recent cloning of complementary DNAs encoding Slo KCa channels has enabled KCa channel modulation to be investigated. We report here that protein phosphorylation modulates the activity of Drosophila Slo KCa channels expressed in Xenopus oocytes. Application of ATP-gamma S to detached membrane patches increases Slo channel activity by shifting channel voltage sensitivity. This modulation is blocked by a specific inhibitor of cyclic AMP-dependent protein kinase (PKA). Mutation of a single serine residue in the channel protein also blocks modulation by ATP-gamma S, demonstrating that phosphorylation of the Slo channel protein itself modulates channel activity. The results also indicate that KCa channels in oocyte membrane patches can be modulated by an endogenous PKA-like protein kinase which remains functionally associated with the channels in the detached patch. PMID- 8202158 TI - Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo. AB - The major regulator of circulating platelet levels is believed to be a cytokine termed thrombopoietin. It is thought to be a lineage-specific cytokine affecting the proliferation and maturation of committed cells resulting in the production of megakaryocytes and platelets. Despite considerable efforts by a number of laboratories, the unequivocal identification of thrombopoietin has proven elusive. Here we report the functional cloning of a murine complementary DNA encoding a ligand for the receptor encoded by the c-mpl proto-oncogene (c-Mpl). The encoded polypeptide has a predicted molecular mass of 35,000 (M(r) 35K). The protein has a novel two-domain structure with an amino-terminal domain homologous with erythropoietin and a carboxy-terminal domain rich in serine, threonine and proline residues and containing seven potential N-linked glycosylation sites. Intraperitoneal injections of mice with recombinant protein increase circulating platelet levels by greater than fourfold after 7 days. These results along with those presented in the accompanying report strongly suggest that the ligand for c Mpl is thrombopoietin. PMID- 8202159 TI - Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin. AB - The development of blood cells including expansion of megakaryocyte progenitor cells requires the interplay of marrow stromal cells and polypeptide cytokines. Recently, characterization of c-Mpl, the receptor encoded by the proto-oncogene c mpl, revealed structural homology with the haematopoietic cytokine receptor family, and its involvement in megakaryocyte development. We report here that the ligand for c-Mpl is relatively lineage specific, works both alone and synergistically with early acting cytokines to support megakaryocyte colony formation, and acts at a late stage of development to increase megakaryocyte size, polyploidization and expression of differentiation markers. In vivo, c-Mpl ligand stimulates platelet production by greatly expanding marrow and splenic megakaryocytes and their progenitors, and by shifting the distribution of megakaryocyte ploidy to higher values. Thus, as c-Mpl ligand has the expected characteristics of the major regulator of megakaryocyte development, we propose that it be termed thrombopoietin. PMID- 8202160 TI - cMpl ligand is a humoral regulator of megakaryocytopoiesis. AB - Megakaryocytopoiesis is the cellular developmental process that leads to platelet production. At least two humoral growth factors may be necessary for megakaryocyte proliferation and maturation. One is a megakaryocyte-colony stimulating factor (MK-CSF) which induces the proliferation and differentiation of megakaryocyte progenitors, and the second, thrombopoietin, is a megakaryocyte maturation factor. Neither of these factors has been fully characterized. The proto-oncogene c-mpl, an orphan member of the haematopoietin receptor family, is specifically involved in megakaryocyte regulation. Here we present evidence that the c-mpl-encoded receptor binds a ligand (c-Mpl ligand) which is a humoral factor implicated in platelet homeostasis. Our results suggest that c-Mpl ligand, thrombopoietin and MK-CSF might be the same molecule. PMID- 8202161 TI - RAD25 is a DNA helicase required for DNA repair and RNA polymerase II transcription. AB - The RAD25 gene of Saccharomyces cerevisiae functions in nucleotide excision repair of ultraviolet-damaged DNA and is also required for cell viability. The RAD25 protein shows remarkable homology to the protein encoded by the human nucleotide-excision-repair gene XPB (ERCC3), mutations in which cause the cancer prone disease xeroderma pigmentosum and also Cockayne's syndrome. Here we purify RAD25 protein from S. cerevisiae and show that it contains single-stranded DNA dependent ATPase and DNA helicase activities. Extract from the conditional lethal mutant rad25-ts24 exhibits a thermolabile transcriptional defect which can be corrected by the addition of RAD25 protein, indicating a direct and essential role of RAD25 in RNA polymerase II transcription. The protein encoded by the rad25799am allele is defective in DNA repair but is proficient in RNA polymerase II transcription, indicating that RAD25 DNA-repair activity is separable from its transcription function. The rad25 Arg-392 encoded product, which contains a mutation in the ATP-binding motif, is defective in RNA polymerase II transcription, suggesting that the RAD25-encoded DNA helicase functions in DNA duplex opening during transcription initiation. PMID- 8202163 TI - A moral question for patent legislation. PMID- 8202162 TI - Insights into autoregulation from the crystal structure of twitchin kinase. AB - Many protein kinases are self-regulated by an intrasteric mechanism where part of the enzyme's structure directly inhibits the active site. This inhibitory structure is called a pseudosubstrate and specific regulators are required to remove it from the active site to allow substrates access. Removal of the pseudosubstrate sequence from members of the myosin light-chain kinase subfamily, including twitchin kinase, activates them but it is not known whether the pseudosubstrate sequence binds to the active site. Native twitchin is a 753K protein (6,839 residues) located in muscle A-bands of the nematode Caenorhabditis elegans and because of its size has not been easy to study. We have determined the crystal structure, refined to 2.8 A resolution, of a recombinant fragment (residues 5,890 to 6,262) of twitchin kinase that contains the catalytic core and a 60 residue carboxy-terminal tail. The C-terminal tail extends through the active site, wedged between the small and large lobes of the structure and making extensive contacts with the catalytic core which accounts for autoinhibition and provides direct support for the intrasteric mechanism of protein kinase regulation. PMID- 8202164 TI - Modeling human motion perception. I. Classical stimuli. AB - Motion perception is one of the most prominent tasks of the visual system and therefore has been extensively investigated both experimentally and theoretically. A classical model describing the mechanism of motion detection originally developed in the context of insect orientation behavior, the elementary motion detector (EMD) of the correlation type, turned out to be very powerful in explaining many basic aspects of human motion perception. For more complex visual tasks, like the discrimination of a figure from its background by relative motion, on the other hand, further processing of motion information is required. In the first part of this review it will be illustrated by means of a few examples, what kind of motion information can be derived from the mere correlation-type model, and what perceptual phenomena can be accounted for by the EMD. In the second part, more recently developed stimuli will be introduced to answer the question what further processing steps, or more sophisticated mechanisms than the EMD, have to be assumed in order to understand "higher" aspects of human motion perception. PMID- 8202165 TI - Subsequent mapping of 137Cs fallout from Chernobyl in Hungary using the radioactivity found in mosses. PMID- 8202166 TI - Collaborate for success. PMID- 8202167 TI - There's nothing wrong? PMID- 8202168 TI - Effects of professional development seminars on role conception, role deprivation, and self-esteem of generic baccalaureate students. AB - This study compared differences in role conception (professional, bureaucratic, and service), role deprivation, and self-esteem among baccalaureate students enrolled in specially designed professional development seminars. More than 100 students participated in the pretests, given on entry to the program, of which 63 completed both the pretest and the posttest given on program exit. The Corwin Role Conception Scale assessed role conceptions and role deprivation and the Coopersmith Adult Form Self-Esteem Inventory assessed self-esteem. Statistically significant differences were found within groups in bureaucratic role conceptions (P = .0009) and self-esteem (P = .0019) and between groups in professional role conception (P = .0057). No differences were found between or within groups for service role conception or role deprivation. PMID- 8202169 TI - From charity to business: community health nursing, 1900-1926. PMID- 8202170 TI - A collaborative model for evaluation of clinical preceptorships. AB - Nurses engaged in practice, recruitment, and staff development were asked to evaluate an educational clinical preceptorship jointly developed by nurse managers and nurse educators. An open-ended six-item questionnaire and a guided telephone interview were used to gather evaluative data. Nursing service respondents valued the precepted clinical experience, not only for the students but for the professional development of the staff participants. The educational clinical preceptorship provided the opportunity for collaboration and the development of collegial relationships between academia and service. An evaluation model evolved that emphasizes the importance of feedback from all participants. PMID- 8202171 TI - An innovative model of system-linked community care: home-based traction as an alternative to institutional treatment. AB - Home-based traction is an alternative treatment to conventional hospital-based traction for children with orthopedic conditions such as congenital dislocated hip and Legg-Perthes disease. The application of a proposed theoretical model is used to describe the process of the home-based traction innovation. Creativity and innovation occasions a reconceptualization of stresses. The reconceptualization of stress, plus the operational support of coordinated in home services, can help families and nurses in the community and in the hospital develop, implement, and evaluate this kind of innovative care. In applying the home-based traction professionals empower and legitimize parents as resourceful co-providers of care. The legitimizing of the alternative in-home service affords parents a more optimistic appraisal of their situation as manageable. Parents are free to develop a coordinated response to their overall circumstance, including the treatment of their one child's illness. The evaluation of this home-based traction example found the alternative to be acceptable, safe, effective in accomplishing treatment goals, and less expensive than conventional hospital based traction. PMID- 8202172 TI - Health care reform: clinical and fiscal responsibility. PMID- 8202173 TI - Nurse executives' responses to ethical concerns and policy formulation for allocation of scarce resources. PMID- 8202174 TI - [Sjogren's disease]. PMID- 8202175 TI - [The future of public health in general and the 'healthy life expectancy' in particular]. PMID- 8202176 TI - [Bacterial vaginosis; pathophysiology and treatment]. PMID- 8202177 TI - [Cleft lip and palate, a continuous problem for the patient?]. PMID- 8202178 TI - [Minor symptoms in family practice; growing pains in children]. PMID- 8202179 TI - [Primary high-dose chemotherapy with hematopoietic growth factors followed by surgery and radiotherapy in stage III breast carcinoma; a Phase II study in 15 patients]. AB - OBJECTIVE: To establish if the prognosis of a stage III breast carcinoma is improved by primary high-dose chemotherapy in combination with haemopoietic growth factors, followed by radical surgery and radiotherapy. DESIGN: Phase II study. SETTING: University Hospital Free University, Amsterdam. METHOD: Fifteen patients with a locally advanced breast carcinoma (stages IIIA or IIIB) were treated every three weeks with doxorubicin 90 mg/sq.m. and cyclophosphamide 1000 mg/sq.m., followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) 250 micrograms/sq.m. from day 2 up to and including day 12. After 4-6 of these courses the treatment in principle was continued with a modified radical mastectomy, followed by radiotherapy. Median duration of follow-up was 18 months. RESULTS: All tumours were reduced by over 50%. 10/15 Patients went into clinical complete remission; in 6/9 of these, pathological examination revealed only microscopical tumour rests, in the other three the rest diameter was < or = 1 cm. The haematological toxicity was mild. Grade III-IV bone marrow suppression was followed by rapid return to normal of the numbers of neutrophil granulocytes and thrombocytes under the influence of GM-CSF. The non-haematological toxicity manifested itself with nausea and vomiting, stomatitis and mild side effects attributable to GM-CSF. CONCLUSION: It appears justified in the treatment of locally advanced breast carcinoma to start with chemotherapy. Dose escalation of efficacious chemotherapeutics resulted in a large number of complete remissions. PMID- 8202180 TI - [Complications shortly after transluminal angioplasty or following coronary surgery in 183 comparable patients with multi-vessel coronary disease]. AB - OBJECTIVE: Description of the differences in complications within 30 days after percutaneous transluminal coronary angioplasty (PTCA) and coronary surgery (CABG) in patients suffering from multiple vessel coronary disease. DESIGN: Prospective, randomised. SETTING: 3 hospitals in the Netherlands. METHOD: Between 1988 and 1992, 183 Dutch patients took part in the European Coronary angioplasty versus bypass revascularisation investigation (CABRI) and were randomly treated with PTCA or CABG. Apart from the clinical result, all complications and cardiac events from time of randomisation until 30 days after the intervention were registered. RESULTS: The CABG group consisted of 88 patients with a total of 255 vascular obstructions, the PTCA group of 95 patients with 294 vascular lesions. In this short period of observation the clinical results of the two treatments were the same. The death rates were 1.1% and 2.1%, for CABG and PTCA respectively. The proportion of transmural, non-fatal myocardial infarctions was 2.3% in the CABG group versus 3.1% in the PTCA group. The proportion of reinterventions was higher in the PTCA group, 11.4% versus 1.1%. CONCLUSION: The differences in death rate and myocardial infarctions are not significant, in contrast to the difference in the numbers of reinterventions. These results appear to be in accordance with those of other randomised studies. Although long term evaluation is needed, treatment of multiple vessel coronary disease by means of PTCA seems a reasonable alternative to coronary surgery. PMID- 8202182 TI - [Integration in medical education: method or fashion?]. PMID- 8202181 TI - [Psychotic reactions during administration of quinolones]. AB - A 86-year-old woman became psychotic one day after starting treatment with 800 mg norfloxacin daily. Discontinuation and short-term treatment with haloperidol were followed by rapid disappearance of symptoms within two days. Since 1984, the Netherlands Centre for Monitoring of Adverse Reactions to Drugs received 19 similar reports of which 12 were attributed to norfloxacin, 3 to ofloxacin and 4 to pipemidic acid. The risk appears to be relatively high in the elderly, especially if they have fever, renal dysfunction and a psychiatric history. Lowering the doses may solve this problem provided the bacterial susceptibility is taken into account. PMID- 8202183 TI - [Strongly variable physiotherapeutic treatment following carpal trauma]. PMID- 8202184 TI - [Medical viewpoints and legal argumentation in war and resistance victims]. PMID- 8202185 TI - [Medical viewpoints and legal argumentation in war and resistance victims]. PMID- 8202186 TI - [Difference of opinion about tube feeding in a patient with dementia]. PMID- 8202187 TI - [Treatment of hirsutism]. PMID- 8202188 TI - The effect of tamoxifen treatment on serum cholesterol fractions in breast cancer women. AB - Serum levels of total, free, HDL- and LDL-cholesterol were determined in 45 postmenopausal breast cancer women treated with tamoxifen (TAM) from 6 to 73 months (mean duration of TAM treatment was 21.3 months) as an adjuvant therapy after mastectomy, and in the control group of 33 breast cancer women at the time of diagnosis before any treatment. The mean age of patients was 63 years in the TAM treated group and 70 years in the untreated breast cancer patients. TAM treated patients were found to have significantly lower concentration of serum total cholesterol (5.43 mmol/l vs. 6.44 mmol/l; p < 0.02) and LDL-cholesterol (3.54 mmol/l vs. 4.32 mmol/l; p < 0.01). There were 8 (18%) hypercholesterolemic patients in the TAM treated group vs. 13 (39%) in the untreated breast cancer patients (p < 0.05). No statistically significant differences were observed in serum concentrations of free and HDL-cholesterol in the two evaluated groups. We conclude that the TAM-induced changes in serum lipid concentrations are due to an estrogen-like activity of the agent and the reduction of total and LDL cholesterol level seems to be an additional advantage of TAM treatment. PMID- 8202189 TI - Gonadectomy abrogates sex differences in the effectiveness of chemical carcinogenesis in mice. AB - Sham-gonadectomized and gonadectomized male and female mice were given methylcholanthrene s.c. to assess the influence of sex hormones on carcinogenesis. Gonadectomy decreased the concentration of the respective sex hormone and increased the concentration of the opposite sex hormone. The results showed that androgens enhanced the effectiveness of carcinogenesis, while estrogens had the opposite effect. Gonadectomy effectively abrogated the sex differences in tumor induction. PMID- 8202190 TI - Clastogenic effects of N-nitrosodimethylamine and dinitrosoglycolurile in murine bone marrow cells and cow lymphocytes. AB - The clastogenic effects of N-nitrosodimethylamine (N-DMA) and dinitrosoglycolurile (DNSGU) were studied in the bone marrow of mice and in peripheral blood lymphocytes of cows. None of the tested compounds showed significant enhancement of chromosome aberrations at doses 1/2 LD50 and 1/10 LD50 in murine bone marrow cells. Treatment of cow peripheral blood lymphocytes with N DMA at concentration of 6 x 10(-5) mol/l (or 12 x 10(-5) mol/l for DNSGU) produced statistically significant increase of chromosomal breaks. The clastogenic effect was also observed in cultures treated with DNSGU at the highest tested concentration (12 x 10(-4) mol/l), but the exposure to N-DMA at parallel concentration had a toxic effect. At the lowest doses of N-DMA and DNSGU (6 x 10(-6) and 12 x 10(-6) mol/l, respectively) no clastogenic effect was obtained. PMID- 8202191 TI - Immunotherapy of superficial bladder tumors: preliminary results with ImmuCyst- BCG Connaught, Toronto. AB - A clinical study has been started in 1991 with ImmuCyst (BCG Connaught) as a secondary prophylaxis in urothelial superficial bladder tumors (SBT) patients. Till now 31 patient have been entered into the trial and the results seem to be promising. Only 2 patients were excluded from the study. Side-effects did not extend in average the data quoted in literature and were easily managed. There were 4 recurrences confirmed by cystoscopy. Urinary infection was treated in 7 cases with current chemotherapeutic drugs. PMID- 8202192 TI - Prevalence of serum IgG and IgM antibodies against Epstein-Barr virus capsid antigen in Indian patients with respiratory tract carcinomas. AB - Antibodies against Epstein-Barr virus capsid antigen (EBV-VCA) were measured in sera of Indian patients with respiratory tract carcinomas (lung, larynx, laryngopharynx, nasopharynx) using a commercial enzyme linked immunosorbent assay (ELISA) kit. Nineteen out of thirty-three (19/33) lung cancer, 12/22 laryngeal cancer, 11/16 laryngopharyngeal cancer, 6/9 nasopharyngeal carcinoma cases and 3/29 matched controls were positive for IgG antibody to VCA. None were positive for the IgM antibody to VCA. The antibody positivity was evaluated on the basis of immune status ratio (ISR) of the sera as described in the manual of the kit. Prevalence of the antibody was more pronounced among smokers with laryngeal and laryngopharyngeal carcinoma than among lung cancer cases. The results indicated that the antibody positivity rate among the patients declined with the advanced stages of the diseases. Serum IgG and IgM levels were raised in the patients who were tested positive for the viral antibody. PMID- 8202193 TI - Evaluation of phthalmustine, a new anticancer compound. I. Effect on Dalton's ascitic lymphoma in mice. AB - The anticancer property of phthalmustine, a hitherto unknown compound containing N-mustard attached to the phthalimide ethyl chain was evaluated using a murine tumor model. The results indicate that the compound was effective in significantly restraining tumor growth. This was accompanied by marked improvement in host survival. No toxic reactions were apparent as reflected in skin and hair texture, body weight and behavioral pattern (food and water intake and activity). Blood picture showed a shift towards the normal following treatment. DNA synthesis in tumor cells was found to be affected as revealed by radioactive thymidine incorporation. PMID- 8202194 TI - Lectin cytochemistry in the exfoliative cytology of uterine cervix. AB - A lectin was isolated from the seeds of jack fruit (Artocarpus integrifolia) and purified using a column of immobilized N-acetyl-D-galactosamine. This jack fruit lectin (JFL) was then conjugated to horse-radish peroxidase (HRP) type VI and used to study the cell surface carbohydrate profile of the cytological smears of the uterine cervix using diaminobenzidine as substrate. Cervical smears from 15 healthy individuals and 65 patients with dysplasia, carcinoma in situ and carcinoma of uterine cervix were used for the study. Normal cells showed weak binding in the membrane as well as cytoplasm, whereas carcinomatous cells showed strong binding towards JFL. Carcinoma in situ cells showed a binding pattern similar to that of carcinoma. Dysplastic cells showed difference in binding in mild, moderate and severe dysplasia. The intensity of binding increased with the severity of the dysplasia. The nature and intensity of binding of jack fruit lectin with cancer tissues suggest that this lectin may be of use as a diagnostic aid in exfoliative cytology. PMID- 8202195 TI - Case-control study of risk factors in laryngeal cancer. AB - A case-control study with 100 cases and 100 controls was conducted to test hypothetical risk factors in laryngeal cancer. McNemar's test helped to select 25 variables, 12 of which were indicated by the conditional logistic regression analysis as independently associated with laryngeal cancer. The association was proved to be statistically significant in the case of seven risk factors; smoking more than 10 cigarettes per day (RR = 18.17; 95% CI 1.95-169.76), predominantly tinned food and meat product diet (RR = 2.65; 95% CI 1.02-6.88), long-term work exposure to low temperatures and building, fabric and metal dust (RR = 4.53; 95% CI 1.80-11.37), extended stay in closed space filled with cigarette smoke (RR = 2.67; 95% CI 1.08-6.60), recurrent hoarseness persisting for more than 1 month (RR = 12.68; 95% CI 3.28-49.03), swollen neck lymph nodes over a number of years (RR = 12.81; 95% CI 1.57-104.29). It was inferred that these seven tested variables could represent risk factors in laryngeal cancer. PMID- 8202196 TI - Enzymes of carbohydrate metabolism in human breast carcinoma: relationship with serum hormones. AB - The enzymes involved in carbohydrate metabolism and their relationship with circulating estradiol (ET2) and prolactin (Prl) were studied in premenopausal and postmenopausal women with fibroadenoma and carcinoma of breast. The activities of all the glycolytic enzymes studied were increased in breast carcinoma tissues except for glyceraldehyde-3-phosphate dehydrogenase which showed decreased activity. Among the glycolytic enzymes studied, hexokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase were found to be stimulated by elevated levels of serum ET2 and further stimulated by a simultaneous increase in Prl. However, the activity of lactate dehydrogenase was more specifically stimulated by Prl rather than ET2. None of the glycolytic enzymes studied was altered in fibroadenoma breast tissues. PMID- 8202197 TI - Serum lactate dehydrogenase and its isoenzymes in leukemia patients: possible role in diagnosis and treatment monitoring. AB - Serum levels of total LDH (T.LDH) and LDH isoenzymes in 145 untreated leukemia patients were examined and compared with those of 150 age and sex matched healthy individuals (controls) and 77 anemia patients (pathological controls). As compared to the controls, T.LDH, LDH-1, LDH-2, LDH-3, LDH-4 and LDH-5 values were significantly elevated (p < 0.001) in untreated leukemia patients. T.LDH, LDH-1, LDH-2 and LDH-3 levels were significantly raised in anemia patients as compared to the controls. A significant increase in the levels of T.LDH, LDH-2, LDH-3 and LDH-4 was observed in untreated leukemia patients as compared to the anemia patients. LDH-4 was most specific (81.0%), while LDH-2 was the most sensitive (84.0%) marker for leukemia. Mean values of all the markers were higher in leukemia patients with persistent leukemic activity/accelerated leukemic phase as compared to the patients in remission. Serum levels of T.LDH as well as all the five isoenzymes were significantly lower in leukemia patients in remission as compared to untreated leukemia patients. The study indicated that alterations in T.LDH and its isoenzymes are useful for diagnosis and treatment monitoring of leukemia. PMID- 8202198 TI - The effect of purine phosphonomethoxyalkyl derivatives on DNA synthesis in CHO Chinese hamster cells. AB - The inhibition of incorporation of 3H-thymidine and the changes of the rate of nascent DNA chain elongation were investigated in CHO Chinese hamster cells treated with (S)-(3-hydroxy-2-phosphonomethoxypropyl) (HPMP) and N-(2 phosphonomethoxyethyl) (PME) derivatives of adenine (A), guanine (G) and 2,6 diaminopurine (DAP). No direct correlation was observed in PME and HPMP derivatives between cytotoxicity, inhibition of 3H-thymidine incorporation and inhibition of nascent DNA chain elongation. The highest cytotoxicity and inhibition of DNA synthesis were caused by PMEG. The limited extent of inhibition of DNA elongation was encountered in the case of HPMPG and HPMPA. With PMEA, weak inhibition of elongation of DNA was observed only after a prolonged exposure (6 h). None of the investigated drugs induced DNA breaks. PMID- 8202199 TI - Pathophysiology of gastro-oesophageal reflux disease. PMID- 8202200 TI - Urinary epidermal growth factor excretion is correlated to renal function loss per se and not to the degree of diabetic renal failure. AB - Urinary epidermal growth factor (EGF) excretion is seen as a marker of tubular function, and some studies conclude that EGF excretion can already be reduced early in the development of diabetic renal disease. It is even suggested that EGF could play a role in kidney and glomerular enlargement and hypertrophy in diabetic subjects. We have investigated various groups of subjects, namely healthy controls (n = 5), patients with non-diabetic chronic renal insufficiency (n = 10), and normoalbuminuric (n = 9), microalbuminuric (n = 13) and nephropathic (n = 9) insulin-dependent diabetic subjects. In all subjects glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured using a continuous infusion of 125I-iothalamate and 131I-hippuran, respectively. Diabetic subjects were tested during (near) normoglycaemic conditions. During the renal function test urine was collected for EGF measurement (in ng). With lower GFR values, EGF excretion/min was also lower. GFR correlated well with EGF/min (r = 0.63, p < 0.001). Fractional EGF clearance (EGF/GFR) was comparable in all groups. There was no correlation between urinary albumin excretion rate and EGF excretion in the diabetic subjects (r = -0.18, n.s.) and in all subjects (r = -0.12, n.s.). There was a significant correlation between UAER and GFR (r = -0.51, p < 0.005). No significant correlation could be found between urinary albumin excretion rate (UAER) and EGF/GFR (r = -0.07, n.s.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202201 TI - Disseminated Penicillium marneffei infection as an imported disease in HIV-1 infected patients. Description of two cases and a review of the literature. AB - Two cases of disseminated Penicillium marneffei infection, as an imported disease, in HIV-1-infected patients with a severe immunodeficiency are reported. These patients had a history of travel in Southeast Asia where P. marneffei is endemic. Fever, cough, malaise, hepatosplenomegaly, anaemia, skin lesions and mucosal ulcers are the main clinical characteristics. Differentiation from histoplasmosis and leishmaniasis might be difficult. Treatment with amphotericin B was successful. Anti-fungal maintenance therapy is most likely indicated. PMID- 8202202 TI - Mycotic aneurysm of the suprarenal abdominal aorta. AB - Staphylococcus aureus is one of the main causes of bacteriaemia. Haemodialysis patients are likely to develop bacteriaemia due to S. aureus, probably because they are often carriers of S. aureus and also frequently have intravascular catheters. This case report describes a very rare complication of S. aureus sepsis in a 62-year-old haemodialysis patient, namely a suprarenal aneurysm of the abdominal aorta. PMID- 8202203 TI - Endothelium and the regulation of vascular tone with emphasis on the role of nitric oxide. Physiology, pathophysiology and clinical implications. AB - After the discovery by Furchgott and colleagues in 1980 that the endothelium plays an obligatory role in acetylcholine-induced vasodilation many investigators have elucidated the role of the endothelium in the regulation of vascular tone. While the sympathetic nervous system serves the organism as a whole, the endothelium appears to act as a local regulator adapting blood flow to local metabolic needs. A variety of endothelium-derived relaxing and contracting factors such as nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor, endothelin and thromboxane A2 play a role in the endothelium-dependent control of vascular tone. Furthermore, nitric oxide inhibits thrombocyte aggregation and adhesion. Many diseases have been reported to be associated with an impaired endothelium-dependent vasodilation which may contribute to an increased susceptibility to vasospasm, decreased inhibition of thrombus formation and an impaired ability to reduce vascular resistance in ischaemic conditions. In hypertension, hypercholesterolaemia and diabetes mellitus this impairment may be interpreted as an early marker of a process that ultimately will lead to atherosclerosis. The impaired endothelium-dependent vasodilation probably contributes to the increased peripheral vascular resistance in hypertension and heart failure. The role of the endothelium does not seem to be restricted to cardiovascular diseases. Several mediators of inflammation stimulate the endothelium to release nitric oxide, suggesting an important role of the endothelium in the haemodynamic sequelae of sepsis. PMID- 8202204 TI - Evaluation of an emergency medical system. The prognosis in patients with an out of-hospital cardiac arrest. AB - In a retrospective chart review, we evaluated the efficiency of the emergency medical system of the Leiden area in patients with an out-of-hospital cardiac arrest. A total of 309 adult patients were included. Two hundred patients (64.7%) died in the emergency department and 67 (21.7%) died during subsequent hospital stay. Finally, 42 patients (13.6%) survived after hospital discharge. Favourable prognostic factors were the presence of witnesses at the time of arrest, a short call-response interval, an initial cardiac rhythm of ventricular fibrillation or tachycardia, and adequate advanced cardiac life support provided by the emergency medical system. We detected several shortcomings in the system such as an unacceptably prolonged call-response interval for some patients at the periphery of the Leiden area and a delay in the first defibrillation attempt. Improvement of this "pre-hospital chain of survival" is likely to result in a better outcome for these patients. PMID- 8202205 TI - Treatment of chronic hepatitis B. AB - Alpha-interferon has emerged as the most effective agent for the treatment of chronic hepatitis when active replication of virus B or D is present. Exogenous administration of human alpha-interferon, now possible through modern large-scale production methods, is associated with disappearance of virus from blood. Amelioration of liver disease occurs in 35% of patients with chronic hepatitis B (e-positive) with interferon doses of 10 MU thrice weekly for 16 weeks; after therapy persistent normalization of serum aminotransferases is observed in 30%. Improvement in liver disease has only occasionally been documented for chronic hepatitis D and for chronic hepatitis B e-minus mutant. Enhanced response rates (> 50%) may possibly be obtained by prolonged intermittent interferon therapy. Combination of interferon with another "antiviral" agent (vidarabine, acyclovir, prednisone) has not increased therapeutic efficacy. Alpha-interferon induces side effects such as fatigue, flu-like syndrome, myalgia and changes in mood. Patients with decompensated cirrhosis are particularly prone to bacterial infection and disease exacerbation and should receive lower-than-normal doses. Interferon, when applied skillfully, induces the highly beneficial transition of active viral replication into viral latency, thereby greatly reducing infectivity, symptoms and activity of the liver disease. PMID- 8202206 TI - Do-not-resuscitate. PMID- 8202207 TI - The frequency of "do-not-resuscitate" order in aged in-patients: effect of patient- and non-patient-related factors. AB - OBJECTIVE: The purpose of this study was to examine the effect of patient- and non-patient-related factors (co-morbidity, demographics, and method of surveillance) on the frequency of "do-not-resuscitate" (DNR) orders in aged inpatients. METHODS: On a geriatric ward, during three different periods within 1 year, we used two different methods of data collection (with or without a form) and two different time-frames (prevalence or incidence) in studying the frequency of DNR orders, demographic data and the Pre-Arrest Morbidity (PAM) Index. RESULTS: In a sample of 261 patients the DNR decision was related to patient related factors, including the PAM score and age. Only 3 patients with a score above 4 had no DNR order and in the group of 142 patients > 83 years 85 (59.9%) had a DNR order, compared to 52 (43.7%) of the 119 patients of 83 years or less (p < 0.05). In contrast, gender and marital status were not related to the presence of a DNR order. The variables PAM score, age, form and time-frame classified 76.6% of the cardiopulmonary resuscitation (CPR) decisions correctly and 71.5% of the DNR decisions correctly. Without attention to the resuscitation decision, the written DNR order frequency decreased significantly from 64-59% to 23%. An explanation for this variance may be the passive process of data collection, a non-patient-related factor. CONCLUSIONS: The DNR decision is related to the PAM index score and age. The variance in DNR decisions is partly related to the method of data collection, a non-patient-related factor in DNR decision-making. Without attention to the DNR/CPR decision, the DNR frequency decreased markedly. PMID- 8202208 TI - Combined treatment with ursodeoxycholic acid and prednisone in primary biliary cirrhosis. AB - OBJECTIVE: To assess the effect of combined therapy (CT) of ursodeoxycholic acid (UDCA) with prednisone on symptoms and biochemistry in patients with non-advanced primary biliary cirrhosis (PBC), who had responded insufficiently to either drug alone. METHODS: Retrospective evaluation of the effect of 1 year of CT on symptoms (pruritus, fatigue, arthralgia) and biochemical parameters [bilirubin, alkaline phosphatase (APh), aspartate aminotransferase (AST) and IgM] in 7 symptomatic patients. RESULTS: Five of the 7 patients became asymptomatic. Pruritus disappeared in 2 of 3 patients, fatigue in 4 of 6 and arthralgia in both symptomatic patients. APh and AST decreased in all patients (median 41% and 59%, respectively). IgM decreased, although to a lesser degree (median 16%), in all but 1 patient. Normal levels for AST were achieved in 4 patients. In 2 of these APh normalized too. In 2 patients IgM became normal. Bilirubin, only slightly elevated in 1 patient, remained stable in all. The beneficial effects were maintained during follow-up (median 1.5 years). The treatment was well tolerated by all patients. CONCLUSIONS: In PBC, combined treatment with UDCA and prednisone appears to improve symptoms and biochemical parameters to a larger extent than either treatment alone; randomized controlled trials should be performed to establish the benefit/risk ratio of this combination therapy. PMID- 8202209 TI - A patient with postpartum primary hypothyroidism and acquired von Willebrand's disease. AB - Patients with hypothyroidism often complain about easy bruising. We describe a patient with a postpartum acquired bleeding tendency. Hypothyroidism was suspected and confirmed biochemically. After substitution therapy with levothyroxine the bleeding tendency recovered completely. The coagulation disorder appeared to be based on an acquired von Willebrand's disease, secondary to the hypothyroidism. In patients with von Willebrand's disease underlying diseases have to be excluded. PMID- 8202210 TI - Transient hypoparathyroidism in a patient with fever. AB - A case history is described of a young man suffering from fever of unknown origin, which was accompanied by transient hypoparathyroidism. There were no indications of a known cause of the hypoparathyroidism. Transient hypoparathyroidism is briefly reviewed and the possibility of parathyroiditis is discussed. PMID- 8202211 TI - Intrahepatic cholestasis and biliary cirrhosis associated with extrahepatic Hodgkin's disease. AB - A 29-year-old male with supraclavicular Hodgkin's disease (Stage IA) developed intrahepatic cholestasis. Cholestasis with severe pruritus persisted while the Hodgkin's disease was brought into remission by radiotherapy. During ursodeoxycholic acid treatment jaundice and hypercholesterolaemia decreased and pruritus disappeared. However, 2 years after diagnosis the patient died of variceal haemorrhage. On autopsy no recurrence of Hodgkin's disease was found. The liver showed advanced biliary cirrhosis. Intrahepatic cholestasis in this patient persisted as a paraneoplastic phenomenon despite complete remission of Hodgkin's disease. PMID- 8202212 TI - p72, a marker protein for melatonin action in ovine pars tuberalis cells: its regulation by protein kinase A and protein kinase C and differential secretion relative to prolactin. AB - The function of the pars tuberalis as a mediator of the action of melatonin remains elusive. As a direct method of assessing the potential role of secretory proteins, ovine pars tuberalis cells have been cultured and radiolabelled with 35S-methionine, and the accumulation of specific radioactive products in the medium, measured after separation by SDS-PAGE and fluorography. The synthesis and secretion of a number of labelled proteins are increased by forskolin (1 microM) and inhibited dose dependently by melatonin (IC50, 300 pM), although consistently a 72-kD protein (p72), is the most intensely labelled of these. Thus, 72 acts as a useful marker of cellular activity for melatonin, whereas prolactin (p23) provides a melatonin non-responsive marker in ovine pars tuberalis cell cultures. The synthesis and secretion of p72 and other melatonin-sensitive proteins is regulated through the cyclic AMP/protein kinase A second-messenger pathway, as analogues of cyclic AMP mimic the action of forskolin, yet 1,9-dideoxyforskolin, a forskolin analogue that is not active on adenylate cyclase, has no effect. However, the phorbol ester, phorbol-12,13-myristate acetate, also regulates the synthesis and secretion of the same profile of proteins as forskolin indicating a potential role for protein kinase C, which occurs through an independent rather than a synergistic pathway. The differential effects of nocadazole (1 microM) and extracellular calcium depletion upon p72 and prolactin secretion indicates that p72 is secreted by a calcium and microtubule independent pathway, in contrast to prolactin. These observations in conjunction with the absence of dense-core storage vesicles in melatonin-responsive cells of the ovine PT are consistent with constitutive secretion of p72 from the latter and regulated secretion of prolactin from melatonin non-responsive cells. Using immunoprecipitation de novo synthesis and secretion of either LH or LH-like proteins from ovine pars tuberalis cells could not be detected under the conditions used. The absence of 125I-(Des-Gly10[D-Ala6]-LHRH-ethylamide) binding over most, but not all, of the ovine pars tuberalis supports the contention that the majority of the cells of the ovine pars tuberalis are not gonadotrophs. These results provide further support for the unique function for the pars tuberalis. PMID- 8202213 TI - Inhibitory effect of arginine-vasopressin on LH secretion in the ovariectomized rhesus monkey. AB - Arginine-vasopressin (AVP) has been previously shown to act in synergism with corticotropin-releasing hormone (CRH) in mediating stress-induced changes in the hypothalamo-pituitary-adrenal (HPA) axis. We have previously shown that both AVP and CRH play a role in mediating IL-1 alpha-induced changes in gonadotropin secretion. In this study, we investigate the effects of exogenously administered AVP on luteinizing hormone (LH) secretion in the ovariectomized (OVX) rhesus monkey. Adult OVX rhesus monkeys were given an intracerebroventricular (ICV) infusion of AVP (15 micrograms/h, n = 8; 50 micrograms/h, n = 5). Control animals received an ICV infusion of physiological saline at a rate 30 microliters/h (n = 12). LH concentrations were measured at 15-min intervals during a 3-hour preinfusion morning baseline and 5-hour postinfusion period. Cortisol concentrations were determined at 45-min intervals. Pulsatile LH release remained unchanged after a control saline infusion. After an AVP infusion, however, LH concentrations (ng/ml) significantly decreased (15 micrograms: from 172.9 +/- 6.4 baseline to 129.4 +/- 5.3; 50 micrograms: from 142.8 +/- 8.3 to 106.7 +/- 6.0, mean +/- SE; p < 0.05). By the fifth hour of the AVP infusion, areas under the LH curve were 64.3 +/- 10.5 and 62.9 +/- 11.0% of morning baseline for 15 and 50 micrograms hourly infusion rate, respectively. While cortisol concentrations decreased throughout the experimental period in the animals receiving saline (a.m.: 35.4 +/- 2.4 micrograms/dl vs. p.m.: 27.7 +/- 1.9 micrograms/dl), they increased after AVP infusion (15 micrograms/h: 42.3 +/- 2.4 vs. 54.6 +/- 2.0 micrograms/dl; 50 micrograms/h: 41.9 +/- 6.6 vs. 50.8 +/- 8.5 micrograms/dl).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202214 TI - Effect of a peripheral and a central acting opioid antagonist on the testicular response to stress in rats. AB - The possible involvement of opioid receptors in mediating the inhibitory effects of immobilization stress on testicular steroidogenesis was determined in adult male rats. Unstressed controls and animals exposed to 3 h of immobilization stress were injected subcutaneously with either vehicle or 1 or 10 mg/kg body weight (BW) of naloxone or naltrexone methobromide (NMB; an opioid receptor antagonist that does not cross the blood-brain barrier) at the beginning of and at 1.5 h of the stress period. Animals were sacrificed at 2 h (30 min after the second injection of antagonist) or 3 h (90 min after the second injection of antagonist) of stress. Plasma LH was not affected by stress, but 30 min after naloxone (1 or 10 mg/kg BW) injection, LH was elevated in both control and stressed rats above levels in vehicle-injected animals. By 90 min after naloxone injection, plasma LH had declined to levels comparable to those in vehicle injected animals. NMB had no effect on plasma LH concentrations in either control or stressed rats. Three hours of stress reduced plasma testosterone (T) levels by 60% in vehicle-injected animals. This effect of stress on plasma T levels was antagonized by the 10 mg/kg BW dose of naloxone and 1 or 10 mg/kg BW of NMB. The ability of naloxone to reverse the effect of stress on plasma T levels was likely related to its ability to stimulate LH secretion, but NMB normalized plasma T values in stressed animals without altering plasma LH concentrations. Only the highest dose of NMB increased plasma T levels in unstressed control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202215 TI - Apomorphine-and oxytocin-induced penile erection and yawning in intact and castrated male rats: effect of sexual steroids. AB - The effect of apomorphine (80 micrograms/kg s.c.) and oxytocin (30 ng i.c.v.) on penile erection and yawning was studied in intact and castrated male rats. In castrated rats both apomorphine and oxytocin responses were abolished. In these animals, testosterone (100 microgramS/kg s.c. once a day for 3 days), restored penile erection while estradiol benzoate (10 micrograms/kg s.c. once a day for 3 days) restored yawning induced by both compounds. 5-Dihydrotestosterone (DHT) or progesterone (each at a dose of 100 micrograms/kg s.c. once a day for 3 days) were ineffective. Given together, estradiol benzoate and DHT partially restored apomorphine- and oxytocin-induced yawning and penile erection, whereas estradiol benzoate and progesterone restored only yawning. Estradiol benzoate-induced recovery of yawning was prevented by the antiestrogen tamoxifen (1 mg/kg s.c. once a day for 3 days). In intact rats, progesterone increased and estradiol benzoate decreased apomorphine- and oxytocin-induced yawning without modifying penile erection, although oxytocin-induced yawning was prevented much less by estradiol benzoate than that induced by apomorphine. Testosterone or DHT were ineffective on both responses. Estradiol benzoate inhibition of apomorphine- and oxytocin-induced yawning was prevented by tamoxifen, which per se failed to modify apomorphine and oxytocin responses, as well as by testosterone or progesterone. The present results suggest that apomorphine- and oxytocin-induced penile erection and yawning are endocrine-dependent and differentially modulated by sexual steroids, suggesting that the mechanisms controlling the two behaviors are different even though they are often associated. PMID- 8202216 TI - Neuroendocrinology of aging in humans: attenuated sensitivity to sex steroid feedback in elderly postmenopausal women. AB - Studies in experimental animals have shown that the sensitivity of the hypothalamic-pituitary system to ovarian sex steroid feedback declines while aging progresses. Since similar observations are lacking in humans, we studied the gonadotropin secretion of postmenopausal women (PMW) of different ages before and following a 7-day course of oral clomiphene citrate (CC, 100 mg daily). For serial determinations of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, blood was sampled frequently from 5 younger PMW (mean age 55.2 years) and 6 older PMW (mean age 80.3 years) for 10 h. Eight hours after initiation of blood sampling, gonadotropin-releasing hormone (GnRH, 25 micrograms) was administered. Compared to untreated conditions, CC administration did not significantly change the serum concentrations of the estrogens (estrone, estradiol) and androgens (testosterone; androstenedione, dehydroepiandrosterone sulfate). However, CC increased the sex hormone-binding globulin levels in both younger and older PMW, suggestive of the estrogenic effects of this compound. In the unstimulated secretory profiles of younger PMW, mean LH levels decreased (p < 0.05) in response to CC, presumably a consequence of decreased (p < 0.05) pulse frequencies, but not pulse amplitudes. Likewise, by virtue of decreased (p < 0.05) FSH pulse amplitudes, FSH levels declined (p < 0.05) in younger PMW. In contrast, both the LH and FSH levels and their pulsatility remained virtually unaltered following CC administrations to older PMW. The GnRH-mediated gonadotropin release was uneffected by CC administrations in either group of PMW.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202217 TI - Identification of receptor-binding pharmacophores of growth-hormone-releasing factor in rat adenopituitary. AB - Previous structure-activity studies on growth-hormone-releasing factor (GRF) have mainly been carried out in pituitary cell culture assays. In such systems, the molecular features necessary to increase GRF receptor affinity cannot be fully distinguished from those that improve proteolytic resistance. To assess the affinity of GRF analogues, we have recently characterized [125I-Tyr10]hGRF(1 44)NH2 binding to rat adenopituitary, developing a reliable binding assay in which GRF-carboxamide-related peptides are stable. In the present study, we have determined the binding affinity of two series of analogues in which the entire sequence of hGRF(1-29)NH2 was scanned with D-amino acid and alanine substitutions. To further document their potency, we have evaluated the ability of representative candidates of each series to stimulate cAMP production. In the first series, a D-amino acid substitution at Ala4, Ile5, Phe6, Thr7, Val13, Gln16, Leu17, Ala19, Arg20 and Ile26 decreased drastically the binding affinity of hGRF(1-29)NH2 while it induced a smaller decrease at Tyr1, Asp3, Ser9, Tyr10, Arg11, Lys12, Leu14, Ala15, Ser18, Lys21, Leu22, Leu23, Gln24, Met27 and Ser28. Interestingly, a D-substitution in position 8 generated an analogue exhibiting a significantly greater binding affinity than hGRF(1-29)NH2, while it had no influence on hGRF(1-29)NH2 affinity at Ala2, Asp25 and Arg29. Adenylate cyclase activities of [D-Tyr1], [D-Tyr10] and [D-Arg20]hGRF(1-29)NH2 correlate with their binding affinity. In the second series, the largest decrease of binding affinity was observed with an alanine substitution at Tyr1, Asp3, Ile5, Phe6, Tyr10, Arg11, Lys12, Leu14, Leu17, Arg20 and Lys21.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202218 TI - Effects of continuous and repetitive administration of a potent analog of GH-RH(1 30)NH2 on the GH release in rats. AB - We examined the desensitization and/or sensitization phenomenon in the pituitary GH responsiveness induced by continuous infusion and multiple pulses at different frequencies of a potent GH-RH analog [D-Ala2, Leu15, Nle27, GABA30-GH-RH(1 30)amide]. Further, we investigated the correlation between doses and GH responses, as well as between pulse frequency and GH responses in male rats in vivo and in vitro. Long-term, continuous administration was attained by osmotic minipumps releasing low and high doses of the analog for 14 days. The effects of repetitive administration of the GH-RH analog on the pituitary GH release was investigated by injecting 4-6 pulses of the analog at different doses and pulse frequencies. The in vitro experiments were performed in the superfused rat anterior pituitary cell system. Pituitary cells were challenged with continuous, repetitive and simultaneous continuous and repetitive perfusion of the analog. Continuous infusion with low doses of the GH-RH analog in vivo induced sensitization of the pituitary GH-secretory responsiveness and resulted in moderately increased GH releases (129% of the control) to additional bolus injections of the same analog, whereas continuous stimulation of the pituitary with high doses of the GH-RH analog evoked desensitization and resulted in blunted GH responses (29% of the control). Despite the desensitization of the pituitary GH-secretory responsiveness, high doses of the analog elevated the serum GH concentration to 310% and induced acceleration of body weight gain (160% of the control). Repetitive pulsatile administration of the GH-RH analog evoked both sensitization and desensitization of the pituitary GH-secretory responsiveness, depending on the dose and pulse frequency administered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202219 TI - Restoration of growth hormone secretion in prolonged food-deprived rats depends on the level of nutritional intake and dietary protein. AB - Prolonged food deprivation inhibits GH secretion in rats. To learn more about the nutritional regulation of GH secretion, we observed whether the recovery of GH secretion from prolonged food deprivation depends on the level of nutritional intake or a specific macronutrient in the refeed meal. Adult male Wistar rats were deprived of food for 72 h. Serial blood specimens were withdrawn via an indwelling right atrial cannula every 10 min using an automatic blood-sampling device. In the 72-hour food-deprived rats, the amplitude of the GH pulse progressively decreased but the pulse frequency did not differ compared to that of the fed control rats. When adult male rats were fed 5, 10 or 40 kcal of mixed meal consisting of carbohydrate 60%, protein 25% and fat 15% after 72 h of food deprivation, both the pulse amplitude and the pulse frequency immediately increased compared to those of the fasted control rats. Following these changes, the pulsatility of GH secretion was restored to normal, while the pulse amplitude was recovered in a meal-size-dependent manner. The GH secretory pattern no longer differed from that of the fed control rats in the rats fed 40 kcal of mixed meal. In the second study, the 72-hour food-deprived rats were fed 10 or 40 kcal of a protein meal consisting only of casein powder or 40 kcal of a protein-deficient meal consisting of carbohydrate 85% and fat 15%. The GH secretory pattern was restored to normal among the food-deprived rats fed 40 kcal of a protein meal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202220 TI - Corticosterone modulates interleukin-evoked fever in the rat. AB - The role of endogenous corticoids in fever responses caused by recombinant murine interleukin (IL)-1 beta and IL-6 was studied in adult male Wistar rats. Adrenalectomy diminished the development of fever after intracerebroventricular (icv) injection of these ILs and lowered body temperature. Intraperitoneal administration of the same doses of ILs did not produce fever in intact animals or hypothermia in adrenalectomized rats, thus suggesting a central site of action of IL-1 beta and IL-6 in these experiments. Chronic replacement with moderate doses of corticosterone restored the fever response in adrenalectomized animals in response to icv administration of IL-1 beta but only partially reversed the fever caused by IL-6. Adrenalectomized animals acutely treated with corticosterone and thereafter with either IL-1 beta or IL-6 developed fever more rapidly than did chronically corticosterone-treated animals. In intact animals corticosterone blocked the fever response to icv injected IL-1 beta. We propose that in the rat corticosterone acts in a bimodal manner on body temperature; it exerts a permissive central effect on the fever response and limits the production of inflammatory mediators in the brain. Conversely, higher corticosterone doses probably reduce the magnitude of the fever response. PMID- 8202221 TI - Hypothalamic PGE2 and cAMP production and adrenocortical activation following intraperitoneal endotoxin injection: in vivo microdialysis studies in Lewis and Fischer rats. AB - Inflammatory disease-susceptible Lewis (LEW) rats exhibit reduced glucocorticoid release in response to inflammatory and neurotransmitter stimuli, compared to histocompatible Fischer (F/344) rats. This compromised hypothalamo-pituitary adrenal (HPA) axis activity has been ascribed to a primary defect in hypothalamic corticotrophin-releasing factor-41 (CRF) secretion, possibly caused by abnormal signal transduction in the CRF neuron. In the present study, we have used in vivo microdialysis to asses the role of hypothalamic prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) in endotoxin-mediated HPA axis activation in adult hyporesponsive LEW and hyperresponsive F/344 rats. Basal plasma corticosterone concentration was significantly higher in F/344 relative to LEW rats; however, the basal levels of PGE2 and cAMP, recovered from microdialysis probes in the anterior hypothalamus, were significantly greater in the LEW rat. Lipopolysaccharide (LPS) (200 micrograms/kg) caused a time-dependent increase in corticosterone secretion, the magnitude of which was markedly greater in the F/344 rat. Both LEW and F/344 rats displayed a similar PGE2 profile in response to LPS, although in absolute terms the response was more pronounced in LEW rats. LPS caused a dose-related increase in cAMP production in the LEW rat and comparison with F/344 animals, following the 200 micrograms/kg dose of LPS, revealed a larger and more prolonged cAMP response in the LEW strain. Simultaneous administration of indomethacin (50 mg/kg) with LPS (200 micrograms/kg) in the LEW rat completely blocked the PGE2 and cAMP responses to the toxin and whilst the corticosterone response to LPS was significantly attenuated at 140 min, no difference was apparent by 240 min. Hence, PGE2 and cAMP participate in the hypothalamic response to endotoxin-mediated adrenocortical activation in both LEW and F/344 adult rats but the steroid and second messenger profiles are strain-specific. The cAMP response to LPS appears to depend on products of arachidonic acid metabolism, such as PGE2, and hence basal and stimulated production of these mediators may be effected by the steroid milieu. PMID- 8202222 TI - Sympathoadrenal regulation of adrenal androstenedione release. AB - The effects of epinephrine and of splanchnic nerve activation on adrenocortical androstenedione release were studied in intact isolated perfused pig adrenals with preserved nerve supply. In addition, long-term effects of epinephrine were characterized in bovine adrenocortical cells in primary culture. To investigate the contact zones of the androgen-producing cells of the zona reticularis with the catecholamine producing cells of the adrenal medulla, cortical cells were immunostained for cytochrome P450 side chain cleavage (P450SCC). Perfusion of the isolated adrenals with epinephrine (10(-7) to 10(-5) M) stimulated androstenedione release in a dose-dependent manner. At a concentration of 10(-6) M, epinephrine provoked an increase to 179.11 +/- 16.14% of basal secretion (p < 0.05). Electrical stimulation of the splanchnic nerves led to an increase to 151.5 +/- 9.24% of basal values (p < 0.05). Epinephrine (10(-6) M) reached 40% and activation of the splanchnic nerves 26% of the stimulatory effect of ACTH at a physiological concentration (10(-10) M). The alpha-agonist phenylephrine had no effect on androstenedione release. In cell cultures, epinephrine stimulated the release of androstenedione in a dose-dependent manner with an ED50 of 0.75 x 10( 6) M. The maximal effect was reached at 10(-5) M with 8.92 +/- 0.66 pmol androstenedione/dish/24 h; the basal secretion was 1.44 +/- 0.54 pmol/dish/24 h. The epinephrine-stimulated androstenedione release was abolished by the beta adrenergic antagonist propranolol while the alpha-adrenergic antagonist phentolamine had no effect. Immunohistochemical staining of paraffin sections of bovine and porcine adrenals for P450SCC revealed that zona reticularis and zona medullaris are closely interwoven.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202223 TI - Neglect of chimeric figures: two halves are better than a whole. AB - From a group of 22 patients with neglect, we identified five patients who neglected the left sides of "chimeric" figures composed of the conjoined right and left halves of drawings of two different objects; these subjects reported the left half-drawing significantly more accurately when a gap was introduced between the chimeric halves. The improvement in the "gap" condition cannot be attributed to the subjects' recognition that the right-sided stimuli were incomplete, as when whole figures were presented on the right along with left-sided half figures, the enhancement in reporting accuracy was maintained. For at least one patient, sufficient information was available about the neglected stimuli to support accurate recognition in a forced-choice task with foils visually similar to the targets. On the basis of these and other data, we propose that for these patients with neglect, visual processing systems subserving the registration of discrete object markers in a spatial map are at least relatively intact, but that there is an impairment in the allocation of attention to the left sides of these markers. PMID- 8202224 TI - The enhanced representation of surface texture consequent on the loss of sight. AB - The unitisation effect in probed feature-recall was exploited to reveal changes in the representation of objects consequent on the loss of sight. Blind and sighted adults were given verbal descriptions of simple objects and later recalled the colour and surface texture of each object. While the blind and sighted were equally capable of recalling an object's colour, the blind were more capable than the sighted at recalling its surface texture. The superior recall of surface texture by the blind emerged very gradually as an increasing percentage of their lifetime was spent without sight. It is concluded that features salient for the haptic sense are increasingly likely to be incorporated in the blind person's representation of objects. PMID- 8202225 TI - The relationship between comprehension and oral reading in progressive fluent aphasia. AB - The role played by comprehension in oral reading was investigated in three patients with progressive fluent aphasia. For patients J.L. and G.C., there was evidence of a deficit in semantic memory affecting both word production and comprehension. F.M., although equally anomic, had significantly better single word comprehension than either J.L. or G.C. It was predicted that, for J.L. and G.C., success or failure in word comprehension should show item-specific correspondence with success or failure in reading exception words, but not regular words. This predicted pattern was obtained between word-picture matching tests and reading. For F.M., with only minimal comprehension impairment for the items used, a smaller trend in the same direction was observed. The results are discussed with respect to Patterson and Hodges' hypothesis (Neuropsychologia 30, 1025-1040, 1992) regarding the consequences of impaired semantic memory for the integrity of representations in the phonological output lexicon. PMID- 8202226 TI - The interaction of lexical and sublexical processes in reading, writing and repetition. AB - It has recently been proposed that in the course of repetition, reading aloud and writing to dictation, lexical representations are activated and selected for output by the joint operation of the semantic system and of sublexical conversion mechanisms--the Summation Hypothesis [Hillis and Caramazza, Brain Lang. 40, 106 144, 1991]. The hypothesis predicts that semantic errors in oral reading and in writing to dictation should only occur when both the semantic system and the sublexical component involved in that task (orthography to phonology and phonology to orthography conversion, respectively) are damaged. The performance of Italian patient E.C.A. indicates damage to the semantic system, and to sublexical phonology to phonology and phonology to orthography conversion mechanisms, but with substantial sparing of sublexical orthography to phonology conversion processes. In agreement with expectations derived from the Summation Hypothesis, E.C.A. produced semantic errors in repetition and in writing to dictation, but not in reading aloud. The paucity of semantic errors in speakers of languages with relatively transparent orthographies is discussed in the context of the Summation Hypothesis. PMID- 8202227 TI - Memory and learning strategies in patients with Parkinson's disease. AB - Parkinson's disease patients (PD) do not differ from control subjects (CS) when they have to execute a problem solving task in which external cues for solving the problem are given. However, when PD have to solve a problem by means of an internally generated strategy, they show a serious decrease in performance. We hypothesised that this distinction may also apply to the way PD and CS organize recall. In order to test our hypothesis the California Verbal Learning Test (CVLT) was administered to 59 PD and 30 CS. The test consists of five learning trials using a 16-word target list, composed of four items from each of four semantic categories. The fact that the word list was built on this implicit organization was not divulged in advance. The sequence in which the words were read is fixed; each subsequent word belongs to a category being different from the category to which the preceding word belongs. The organization in recall according to the semantic categories is considered to be the result of an unprompted, internally generated strategy. Recall according to the sequence in which the words are read by the experimenter, is viewed as an externally offered strategy. The results prove to be in line with our hypothesis: unlike CS who appeared to rely mainly and increasingly on an internally generated semantic organization, PD showed evidence of gradually adhering more to the externally imposed serial sequence. PMID- 8202228 TI - Priming in perceptual identification of pseudowords is normal in Alzheimer's disease. AB - Patients with Alzheimer's disease (AD) have deficits in recall and recognition memory, and show dissociable performance in repetition priming tasks: They exhibit impaired priming in word-completion and word-generation tasks, but normal priming is perceptual identification of words. In order to examine whether AD patients can show normal priming with novel, unfamiliar stimuli, the present study examined their performance in perceptual identification of pseudowords. Despite impaired recognition memory performance, AD patients showed normal priming in perceptual identification of pseudowords. These results extend the boundaries of intact repetition priming in AD, demonstrating that such priming is not limited to stimuli that are pre-morbidly represented in long-term knowledge. Preserved repetition priming in AD may reflect the operation of perceptual processes localized to posterior visual circuits that are relatively spared in AD. PMID- 8202229 TI - The Benton-Van Allen faces: a lateralized tachistoscopic study. AB - The Benton-Van Allen Facial Recognition Test (FRT) was adapted to a lateralized same-different task. The lateralized same targets were either physically identical to the central upright faces or had the same face identity but were transformed (3/4-views or shadowed faces). Faces were also modified to include or exclude external features. There was a left hemifield (right hemisphere) advantage only for the most difficult, shadowed faces. The absence of a left hemifield advantage for the matching of upright faces to identical or 3/4-view faces shows bilateral competence for face processing, both by physical and by face identity, and confirms previous observations that the FRT does not discriminate left from right hemisphere-damaged patients. Removal of external features affected performance in the right but not the left visual field, suggesting that the left hemisphere uses a less feature-dependent mechanism than the right hemisphere. This effect was only present in females, who were more lateralized than males. PMID- 8202230 TI - Chronic headache: appropriate use of opiate analgesics. AB - The question of the appropriate use of opiate analgesics in the management of chronic headache pain is under debate. Often, the management of headache pain is complicated by the overuse of dependency-promoting analgesics. Because of confusion about the use of analgesics in pain management, some patients are denied access to necessary opioid analgesia, whereas others receive large quantities of combination analgesics. The proper use of opiate analgesics is presented here, including a review of the pharmacology of these agents. Signs of analgesic dependence, analgesic rebound headache, and methods of withdrawal are also presented. The potential use of such new treatment modalities as butorphanol nasal spray is discussed. PMID- 8202231 TI - Recurrent migraine: cost-effective care. AB - The cost of untreated or ineffectively treated migraine is staggering. A case study is presented that demonstrates the importance of developing an individually tailored home treatment program for migraine patients aimed at keeping them out of healthcare facilities on an acute basis. Treatment programs should include preventive medications if attacks occur more than twice per month, as well as appropriate abortive and symptomatic agents in the event of a severe, acute migraine attack. New agents and treatment modalities are making acute treatment more cost-effective and making it less likely that unnecessary time be spent seeking medical help at the time of an attack. PMID- 8202232 TI - Diagnosing the severe headache. AB - A patient's medical history, age of onset, location of pain, pain characteristics, pain chronology, associated signs and symptoms, and signs of neurologic dysfunction are all important considerations in making a diagnosis. The International Headache Society has developed a thorough classification system to aid in the diagnosis of headache, which includes primary disorders of migraine, tension-type headache, and cluster headache, as well as secondary, organic disorders. PMID- 8202233 TI - Effects of cryoprecipitate on the healing of chronic wounds. AB - Basic research has promise for clinical wound healing. Purified wound healing growth factors are not available for clinical use, but they are present in plasma and platelets and have been used in patients. Chronic wounds would seem to be good for study since the wound surface is easily measured and the patient is anxious for progress. We have done a double-blinded pilot study using autologous cryoprecipitate on chronic wounds. Three of six patients showed wound healing progress; but only one patient's wounds healed permanently. One patient developed new diabetic ulcers, and one patient failed to keratinize epithelialized skin. Cryoprecipitate may promote wound healing, but further work awaits more purified healing factors. Simple measurement of the surface area of a chronic wound may not be adequate to describe all the processes of healing. PMID- 8202234 TI - Exacerbation of asthma after pyridostigmine during Operation Desert Storm. AB - Pyridostigmine was first used extensively during Operation Desert Storm for prophylaxis against the effects of nerve agents. After initial reports of asthma exacerbations following its use, we gave 10 asthmatic and 6 non-asthmatic soldiers a 30-mg dose of pyridostigmine. We found no changes in forced vital capacity in any of the soldiers, but observed exacerbation of asthma symptoms in seven of the asthmatics. Severity of the exacerbation correlated best with severity of asthma in the desert and inversely with body weight. The irritant effect of the dust may predispose asthmatics to worsen after pyridostigmine, an effect not seen in the laboratory. PMID- 8202235 TI - Psychosocial factors influencing smokeless tobacco use by teen-age military dependents. AB - Using bivariate and logistic regression analysis, we explored psychosocial correlates of smokeless tobacco (SLT) use in a sample of 2,257 teenage military dependents. We built separate regression models for males and females to explain triers and users of SLT. Results show female and male triers share five factors regarding SLT use--parental and peer approval, trying smoking, relatives using SLT, and athletic team membership. Male trial of SLT was additionally associated with race, difficulty in purchasing SLT, relatives who smoke, current smoking, and belief that SLT can cause mouth cancer. Male use of SLT was associated with race, seeing a dentist regularly, SLT counseling by a dentist, parental approval, trying and current smoking, and grade level. In all models, trying smoking was the strongest explanatory variable. Relatives and peers exert considerable influence on SLT use. Few triers or users had received SLT counseling from their dentist despite high dental utilization rates. PMID- 8202236 TI - The effect of Aviation Officer Candidate's School on aerobic and anaerobic fitness. AB - The purpose of this study was to determine the effect of Aviation Officer's Candidate School (AOCS) on the aerobic and anaerobic fitness of the candidates. Thirty candidates were tested prior to and post-AOCS. Anaerobic measures included vertical jump and seated shot-put throw. A 1.5-mile run was used as an aerobic measure. Timed push-ups and sit-ups were used as overall strength and endurance measures. Body fat was assessed by OPNAV 6110.1 standards. Statistically significant increases were achieved in all areas, except for body fat and push ups, which produced no significant changes. PMID- 8202237 TI - Cold-weather field feeding: an overview. AB - Extremely cold environments are a challenge to military field feeding operations due to freezing and inadequate intakes of rations and water. The U.S. Army Research Institute of Environmental Medicine conducted a series of three cold weather field feeding studies to test, modify, and contribute data for the development of Cold-Weather Feeding Doctrine. Conclusions from these studies show that command emphasis is essential for ration and water storage and distribution to prevent freezing, and adequate ration and water consumption to prevent weight loss and dehydration. Since any ration mix can be configured to meet cold-weather feeding requirements, the decision of which ration to use should be based on logistical support and constraints, mission requirements, and water availability. PMID- 8202238 TI - Source of health care for military dependents with cystic fibrosis. AB - Health care to military dependents with cystic fibrosis (CF) may be compromised by lack of consistency. Civilian centers provide an alternative for care. A reliable count of dependents with CF is unknown. We surveyed 196 military treatment facilities (MTFs) to obtain data on dependents with CF and compared it with data from the National CF Registry. Seventy-seven percent of the MTFs responded and 143 patients were identified. Registry data identified 373 CHAMPUS patients at 82 civilian centers. There were 284 patients in the Registry only and 54 patients in the MTF survey only. Eighty-nine patients were identified through both data sources. A total of 427 patients were identified. Under current CHAMPUS reorganization plans, MTFs will serve as "gateways" for funding of specialized civilian care. Thus, the influx of these and other chronically ill children into the MTF may tax the resources and capabilities of these facilities. PMID- 8202239 TI - Foot blister risk factors in an ROTC summer camp population. AB - Data that establish risk factors for foot blister morbidity among ROTC cadets at summer camp are presented. The subjective blister attack rate was 42.1 per 100 cadets. Women had a relative risk of 1.6 that of men (p < 0.001). Cadets with a history of blisters in the 2 years before camp had an increased relative risk of blister formation. Cadets who reported wearing their boots less than 20 hours per week during the 2 weeks immediately before camp had elevated risk. Other factors are examined. These data suggest that the foot must become conditioned to its footwear to prevent blister formation. PMID- 8202240 TI - Treatment needs and treatment time for soldiers in dental fitness class 2. AB - A systematic random sample of 962 dental records of soldiers in class 2 was reviewed by six general dentists and their estimates of periodontal and non periodontal treatment time were recorded. The majority (88.9%) required some treatment. Periodontal treatment time ranged from 0 to 18 hours with a median and mode of 0 hours, a mean of 1.18 hours, and a standard deviation of 2.96 hours. Non-periodontal treatment time ranged from 0 to 58 hours with a median of 3 hours, a mode of 0 hours, a mean of 4.51 hours, and a standard deviation of 5.11 hours. When consultation time is included, the total time was 5.89 hours per soldier. PMID- 8202241 TI - Young male suicide attempters 20 years later: the suicide mortality rate. AB - In a 20-year, register-based follow-up of a group of 51 young male conscripts who had made a suicide attempt during their service, 2 were found to have committed suicide during the follow-up period. These figures gave a 20-year accumulated suicide mortality of 3.92%, whereas the corresponding value in the cohort of Norwegian males who reached the age of 20 in the period 1968-1972 was 0.40%. In spite of this clear difference, the study indicates that the long-term suicide mortality is relatively low for young suicide-attempters in this type of setting compared to figures from other follow-up studies. PMID- 8202242 TI - Do follow-up home visits by military nurses of chronically ill medical patients reduce readmissions? AB - The study included patients admitted three times or more. Patients were 45 years of age or older and lived within 25 miles of the hospital. Patients were randomly assigned to a control group and those that received home visits. Patients were visited by the RN within 7 days after discharge. Each patient had nine visits over the next 3 months. Seventy-five patients participated in this study. The average age of the sample was 66.12 +/- 16 years. There was an equal number of men and women in the two groups. The nurses made 130 home visits. During these visits, 38 interventions were accomplished. These interventions allowed the patients to remain at home. Prior to this study, the incidence of readmission for these patients was notable. This study showed that home visits with appropriate interventions by military staff nurses reduces the incidence of rehospitalization. PMID- 8202243 TI - Demographics of Military dependent children and adolescents: projected patient population shift. AB - The United States government provides health care for one of the largest beneficiary populations in the world. Approximately 796,500 (35%) of the 2.27 million dependent children of uniformed services personnel are adolescents (13 to 19 years old). Although the majority of dependent children are dependents of active duty personnel (74.7%), close to half of the adolescents (47.7%) are dependents of retired personnel. Recent geopolitical world changes and a perceived decreased threat to national security have led to a planned 25% reduction of the active duty force by 1996. The mean age of children beneficiaries will rise as a result. Pediatricians in the military and civilian contract physicians need to prepare for increased health care of older pediatric patients, particularly adolescents. PMID- 8202244 TI - A simple suction device for aeromedical evacuation. AB - A design for a continuous multi-port suction device for C-130 tactical aeromedical evacuation is presented. It utilizes existing aircraft systems and can be built in minutes using little more than plastic tubing. The concept could also be extended to other aircraft. PMID- 8202245 TI - Haitian mass migration: Uniformed Service medical support, May 1992. AB - Beginning in November 1991, the United States Department of Defense established a Joint Task Force (JTF) to deal with the mass migration of Haitians. During the next 9 months, pending a determination of their immigration status, 34,000 Haitians were managed by uniformed service personnel at a temporary camp facility at the U.S. Naval Base in Guantanamo Bay, Cuba. To meet the urgent clinical and public health needs of this population, the JTF developed a camp medical system. This article describes the system of uniformed service medical support for the Haitians at the Guantanamo Bay facility during May 1992, the busiest month of the operation, when 11,400 Haitians (34% of the total) arrived. PMID- 8202246 TI - Use of routine laboring epidurals at Naval hospitals: a physician survey. AB - Physicians and patients have complained about a lack of laboring epidurals at Naval hospitals. In order to assess this situation, a survey was mailed to all physicians specializing in obstetrics and gynecology (OB) and family practice who were stationed at Naval hospitals in the United States and abroad. Respondents were queried regarding the availability of routine laboring epidurals (RLEs) at their hospitals, as well as their attitudes toward the use of RLEs. RLEs were reported to be available for most patients who might benefit at OB teaching hospitals but not at other Naval hospitals. Most physicians stated that patients complained about a lack of RLEs and that the patient could obtain one at a civilian hospital in the area. Most physicians, especially OBs, had favorable attitudes regarding the use of RLEs and would employ them if available. The discussion includes how the Department of Defense has taken steps toward making epidurals available to all military women and dependents. PMID- 8202247 TI - Oriental cholangiohepatitis. AB - Oriental cholangiohepatitis (OCH) is a disease endemic to Asia. U.S. military physicians and surgeons deployed to these regions should be aware of this regional disease. Western physicians encounter OCH with the increasing immigration of Asians to the United States. OCH should be suspected in patients with signs of cholangitis who have traveled from Asia. Initial treatment is medical with antibiotics and identification of helminthic and parasitic infection. Unless there is inadequate response to medical treatment, surgery is delayed. Operation consists of exploration and drainage of the common bile duct. Overall results are satisfactory with prompt recognition and appropriate medical and operative treatment. PMID- 8202248 TI - Fatal rhabdomyolysis presenting as mild heat illness in military training. AB - A 30-year-old black male soldier with sickle cell trait presented with fatal exertional rhabdomyolysis (which was unrecognized during 14 hours at a field clinic). After prompt treatment for heat exhaustion, his symptoms seemed mild and he was afebrile. His clinical course illustrates the potential for severe illness in the absence of fever, the importance of assessing mental dysfunction, indications for laboratory evaluation, the need for comprehensive management of severe dehydration and acidosis, common laboratory features of acute renal failure and exertional rhabdomyolysis, and the increased risk of exercise-related death in those with sickle cell trait. PMID- 8202249 TI - Traumatic hemipelvectomy: a survivable injury. AB - Traumatic injury remains an unfortunate and all-too-common event in the United States military population. Traumatic hemipelvectomy is a rare but devastating injury with few survivors recorded in the medical literature. We report a surviving case of traumatic hemipelvectomy and review an approach to management. PMID- 8202250 TI - Paraganglioma of the vagus nerve masquerading as a carotid body tumor. AB - A case of paraganglioma of the vagus nerve in a 69-year-old woman presented as a pulsatile neck mass of 20 years duration. Angiogram showed it to be a vascular tumor and suggested the diagnosis of carotid body tumor. At operation, the tumor was found to involve the vagus nerve, which needed to be resected. The relevant literature regarding paragangliomas of the vagus nerve is discussed. PMID- 8202251 TI - The quest for ethical leadership in military medicine. PMID- 8202252 TI - WESTPAC, AIDS, and the Navy. PMID- 8202253 TI - Evaluation of aging pilots: evidence, policy, and future directions. AB - Current Federal Aviation Administration (FAA) regulations require that pilots of large commercial passenger and cargo aircraft be under age 60. However, the requirement does not apply to other pilots and the courts have ruled that mandatory retirement of test pilots at age 60 violates the Age Discrimination in Employment Act. FAA medical standards establish three levels of medical qualification, which require certain age-specific screening tests. This paper reviews the epidemiologic and clinical evidence relevant to the evaluation of aging pilots. This evidence is compared and contrasted with the current FAA requirements and past recommendations of the American Medical Association, the Institute of Medicine, and the Office of Technology Assessment. An opportunity exists to assess the class I examination and other tests through the consent decree covering aging test pilots. Another course of action would be to implement special issuances for older pilots. PMID- 8202254 TI - Anesthesia in northern Iraq: an audit from a field hospital. AB - A Royal Naval field surgical team deployed to Iraq for 6 weeks. Seventy-one anesthetics were administered to 52 patients. The Triservice anesthetic apparatus (TSA) was used with controlled ventilation and either halothane plus trichloroethylene or isoflurane. Other techniques included spontaneous ventilation via the TSA, ketamine and midazolam, either with or without controlled ventilation, or local anesthesia. A simple modification allowed preoxygenation with 100% oxygen. Controlled ventilation with air alone was usually associated with satisfactory pulse oximetry and oxygen economy. Isoflurane was not significantly hypotensive and recovery was more rapid than with halothane/trichloroethylene. Drawover techniques with controlled ventilation were satisfactory for children as small as 6.5 kg. Overnight ventilation was instituted on three occasions, and it was found that a simple positive end expiratory pressure system could be applied to the Laerdal valve. Pulse oximetry, ECG, and automatic arterial pressure monitoring facilities were used. The total drug expenditure for all 71 anesthetics was only $178. PMID- 8202255 TI - Proliferative activity as an adjunct in the diagnosis of prostatic adenocarcinoma. AB - Sixty-nine men underwent transrectal ultrasound-directed biopsy of the prostate. One biopsy core from each side of each gland was sent for DNA flow cytometric testing (138 total specimens). Results were correlated with findings from standard hematoxylin and eosin staining of other cores. Twelve patients (17.4%) had biopsies with histopathologic evidence of prostatic carcinoma. Of 57 patients (82.6%) with benign biopsies, two had stage A prostate adenocarcinoma noted on subsequent transurethral resection. Proliferative activity was calculated from DNA histograms by adding the percentage of nuclei in the proliferative (S and G2/M) phases of the cell-division cycle. Mean proliferative activity for the malignant group (19.08) was significantly higher (p < 0.001) than that of the benign group (13.43). Inflammation was associated with elevated proliferative activity scores among benign glands. Proliferative activity is an objective, easily obtainable indicator of the biological activity of a population of cells which, when elevated, may suggest a need for repeat biopsy in patients with otherwise normal prostate biopsies. Flow cytometry may have value as a complement to standard histologic analysis of transrectal core biopsies in the diagnosis of prostate cancer. PMID- 8202256 TI - Inter-operability of health services of the coalition forces: the Hungarian Military Hospital's experience in the Persian Gulf War. AB - The purpose of this paper is to study the inter-operability of allied-nation health service support systems working together in support of a combined operation. The Republic of Hungary contributed a military hospital to the Coalition Forces' Health Service Support in Operation Desert Storm. The experience of this hospital was unique. This hospital was incorporated into a western military health service system, which was alien to its organization and doctrines. The hospital's organization was based on the requirements of the former Warsaw Pact and followed Soviet doctrine. The author summarizes the experience of medical professionals and non-medical operational conditions during Operation Desert Storm and highlights the similarities and differences of the two systems. He also makes recommendations to promote military medical inter operability. PMID- 8202257 TI - Report on the Hungarian Military Health Service Support (a former Soviet dominion). AB - The author describes the structure and organization of the Health Service Support of the Hungarian Armed Forces. The differences and similarities between the U.S. and the Hungarian Military Medical Services are highlighted. The potential for inter-operability is examined. The importance of such considerations is marked by the ongoing hostilities in the former Yugoslav Republic. PMID- 8202258 TI - Continuity and change in father-adolescent relations. PMID- 8202259 TI - Distinctive role of the father in adolescent separation-individuation. PMID- 8202260 TI - Men in midlife and the quality of father-adolescent communication. PMID- 8202261 TI - Finding time for fatherhood: the emotional ecology of adolescent-father interactions. PMID- 8202262 TI - Values and communication of Chinese, Filipino, European, Mexican, and Vietnamese American adolescents and their families and friends. PMID- 8202263 TI - Father-adolescent relationships: from phase 1 findings to phase 2 questions. PMID- 8202264 TI - HIV clinical guidelines. PMID- 8202265 TI - AIDS. PMID- 8202266 TI - Clinical consequences of the Diabetes Control and Complications Trial. AB - The DCCT has settled the question of the relationship of diabetes control to diabetes complications. By utilizing intensive diabetes therapy, the DCCT was able to reduce the risk of diabetes complications by 50 to 75 percent. As practicing physicians, in the era of health care reform, we must devise methods to bring quality diabetes care to our patients with diabetes in a cost-effective manner. SDM is a system for providing this quality, cost-effective effective care for patients with diabetes. PMID- 8202267 TI - Implications of the DCCT for children and adolescents with IDDM. AB - The DCCT findings have unique implications for youth with diabetes. Attempts should be made to achieve improved glycemic control in all children and adolescents with diabetes, but particular care needs to be exercised to avoid untoward side effects, especially hypoglycemia. PMID- 8202268 TI - Current thoughts on diabetes patient education in New Jersey. AB - The DCCT study proved that the incidence of long-term complications of diabetes mellitus decreases with improvement of blood glucose control. The health care team management approach for patients with diabetes mellitus has been demonstrated to result in improved metabolic control. PMID- 8202269 TI - Type II, noninsulin dependent diabetes, IGT, and H-IRS. PMID- 8202270 TI - Standards of diabetes care in primary care medicine. AB - Patients with diabetes need specific treatment and education about their disease. The goals of therapy include the maintenance of normal health and the prevention of the progression of the metabolic abnormalities and complications of diabetes. PMID- 8202271 TI - The diabetic diet: a model for Americans. AB - The nutrition management of individuals with diabetes mellitus now closely parallels the goals of the model American diet. Emphasizing this positive relationship with the use of team education and treatment will improve clinical success and enhance the quality of life for people with diabetes. PMID- 8202272 TI - Eye care: diabetic retinopathy. AB - Diabetic retinopathy is the leading cause of blindness in the United States for adults, ages 20 to 74 years. Yet, the strict control of blood glucose may help ameliorate the potentially catastrophic effects of diabetes on vision. Physicians need a working knowledge of diabetic retinopathy. PMID- 8202273 TI - Caring for the diabetic: assessing risk in the diabetic foot. AB - The initial diabetic foot evaluation should be completed with ease and reliability. The first preventive step involves identification of primary findings of the dermatologic, musculoskeletal, vascular, and neurologic systems, coupled with the presentation of educational information. PMID- 8202274 TI - Lower extremity amputations in New Jersey. AB - We compared the incidence of nontraumatic lower extremity amputations in the diabetic and nondiabetic populations in New Jersey. The diabetes-related lower extremity amputation rate was 80.1/10,000 diabetic population, while the rate for nondiabetes-related amputations was 1.6/10,000 population. PMID- 8202275 TI - Diabetes mellitus: a frequent factor in liability claims. AB - Inappropriate treatment of diabetes mellitus is the cause of an increasing number of malpractice claims. The authors present pertinent trends elicited by an analysis of diabetes claim files and their possible prevention. Files from February 1, 1977, to February 1, 1992, were reviewed. PMID- 8202276 TI - Physician education on five complications of diabetes mellitus. AB - Five roving symposia series directed to primary care physicians addressing the complications of diabetes were designed, implemented, and evaluated. These roving symposia effectively reached physicians statewide and appeared to influence positive practice behaviors. PMID- 8202277 TI - Research shows AZT therapy reduces mother-child AIDS transmission. PMID- 8202278 TI - Transport and metabolism of vitamin A. PMID- 8202279 TI - Cellular transport and metabolism of vitamin A: roles of the cellular retinoid binding proteins. PMID- 8202280 TI - Vitamin A in embryonic development. PMID- 8202281 TI - Vitamin A receptors. PMID- 8202282 TI - Vitamin A in epithelial differentiation and skin carcinogenesis. PMID- 8202284 TI - Vitamin A: its effect on childhood sight and life. PMID- 8202283 TI - Vitamin A and cancers of the breast, large bowel, and prostate: epidemiologic evidence. AB - In this review we have examined epidemiological data from a variety of sources to assess the relation between vitamin A intake and cancer risk. The potential for recall bias in case-control studies makes their interpretation difficult, particularly if we are searching for modest associations. Prospective data are preferable, but sparse. Studies of blood levels of carotenoids may be informative if the blood is stored at ultra-low temperatures; however, studies of blood retinol levels are largely uninformative as an index of dietary intake because blood retinol is not well correlated with intake except in vitamin A-deficient populations. We have also reviewed the evidence for an influence of vitamin A intake on the incidence of cancer at the three major cancer sites accounting for a substantial portion of cancers in developed countries. The available data are compatible with a modest inverse association between intake of vitamin A and breast cancer, although it is not clear whether this effect may be due to preformed vitamin A, carotenoids, or both. The evidence that vitamin A protects against colon cancer is unconvincing. In the case of prostate cancer, early suggestions that vitamin A may increase incidence have not been confirmed by subsequent studies. Fortunately, prospective data from a number of large ongoing cohort studies in the United States and Europe should be available within the next 5 years or so. These data will permit further assessment of potential correlations between vitamin A and cancer at various sites by analysis of much larger numbers of cases than are presently available.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202285 TI - Needs and sources of carotenoids and vitamin A. PMID- 8202286 TI - Risk factors for small for gestational age infants: a New Zealand study. New Zealand Cot Death Study Group. AB - AIM: The aim was to identify risk factors for small for gestational age infants. METHOD: Case-control study. The study population was 1800 infants selected randomly from all babies born over a three year period over 78% of the country. Of these 1800 infants, 85 (4.8%) were classified as preterm (< 37 weeks completed gestation) and were excluded. 157 (8.9%) were classified as small for gestational age (cases) and 1519 (86.3%) were fullterm, nonsmall for gestational age infants (controls). Risk factors were investigated using data collected from obstetric records and parental interviews. RESULTS: Risk factors associated with small for gestational age after controlling for potential confounders included maternal smoking during pregnancy (Odds ratio (OR) 2.61, 95% confidence interval (CI) 1.65, 4.15), primiparity (OR 2.96, 95% CI 1.59, 5.48), lack of antenatal care in the first trimester (OR 1.83, 95% CI 1.13, 2.98) and young age when mother left school (OR 1.56, 95% CI 1.01, 2.41). Use of marijuana in pregnancy significantly increased risk of small for gestational age at the 6% level (OR = 1.86, 95% CI 0.98, 3.52). The population attributable risk for maternal smoking was 31.1% (95% CI 18.2, 41.9). CONCLUSION: Maternal smoking was the most important modifiable risk factor in this dataset for small for gestational age. PMID- 8202287 TI - Self management practices in adult asthmatics. AB - AIM: To examine how adherence to medications and use of competencies (eg, avoiding personal precipitants and managing an acute attack) vary by age, sex, education and number of symptoms in a sample of adult asthmatics. METHODS: 412 adult asthmatics, members of two asthma societies, participated in a mailed survey. The questionnaire contained measures of asthma medication adherence, asthma health competencies, asthma symptoms, and demographic characteristics. RESULTS: Older asthmatics were more likely to adhere and to use more competencies. Females used more competencies than males. Asthmatics with higher numbers of symptoms used more competencies. No differences were found by educational level. CONCLUSIONS: Better adherence in older asthmatics may be due to their having developed greater recognition of the efficacy of medications. The more extensive use of competencies by older people and by women reflects previous findings that these groups value health more and engage in less health threatening behaviours in general. The results also suggest that experiencing asthma symptoms motivates better self management practices. The study raises awareness of the role of competencies in controlling asthma, and should assist health professionals to identify specific differences in self management. PMID- 8202288 TI - Vexation in the voluntary sector. PMID- 8202289 TI - Amputations in the surgical budget. AB - AIM: To describe the extent and distribution of in patient costs of nontraumatic lower limb amputations and to identify areas of high cost as a basis for cost saving strategic planning. METHODS: Retrospective review of 134 consecutive admissions resulting in lower limb amputations for reasons other than trauma over a 33 month period. General surgical and orthopaedic costs were compared. More detailed cost distribution analysis was then conducted for a group of general surgical amputees corroborating data from the resource utilisation system, Otago surgical audit and patient records. RESULTS: The mean cost of admission for nontraumatic lower limb amputations performed by general surgeons was $11,342 (median $21,439 range $144-$43,022) and was significantly more expensive than orthopaedic amputations, mean $2318 (median $6277 range $307-$13,907) p < 0.001. Of general surgical patients, 38.7% had diabetes and these accounted for 36.1% of total costs. Most amputations (73.9%) in diabetics were of the minor type compared with 29.0% in the nondiabetic group (p < 0.001). Ward costs accounted for the largest proportion of total cost 55.6% (95% CI 45.1, 66.0). For major amputees 40% (95% CI 31.4, 48.1) of in-hospital time was used for rehabilitation. CONCLUSION: Nontraumatic amputations are costly. Diabetics, having mainly minor amputations, account for a disproportionate amount of the cost. Length of hospital stay is the most important determinant of cost, much of which is spent on rehabilitation. A case is made for early definitive surgery and a greater use of community based services and low cost centres in rehabilitation. PMID- 8202290 TI - Introduction of continuous regional techniques for postoperative paediatrics patients: one years' experience from two hospitals. AB - AIM: To review the use, safety and efficacy of continuous regional techniques in children and neonates. METHODS: The records of all children who received postoperative continuous regional analgesic techniques during the year 1992 at the Starship Children's Hospital and Waikato Base Hospital were reviewed. In both post operative care units orders, procedures and protocols were standardised. RESULTS: A total of 80 children received these techniques. Patients were cared for in high dependency nursing areas. The two techniques used were epidural and interpleural analgesia. Epidural: The majority (68) had epidural catheters and of these 13 infants were in their first month of life. Major problems occurred in six (9%) of children receiving epidurals--two blocks failed completely, two suffered subarachnoid puncture, one had respiratory depression and one developed a foot-drop. The blockade failure and subarachnoid punctures occurred early in the establishment of paediatric epidural analgesic services. Minor problems included the necessity for morphine supplementation in three (4%) children, leaks about the catheter in seven (10%), nausea and vomiting in six (9%), two (3%) developed pruritus and one block was ceased because of concerns expressed about masking symptoms of compartmental compression. Interpleural: twelve patients were treated with this technique. One neonate suffered a convulsion. CONCLUSION: Major continuous regional techniques in paediatric patients are effective, but because of potential complications, there is a requirement that these blocks be performed, monitored and cared for by staff experienced and trained with these procedures. PMID- 8202291 TI - Tetanus in Auckland: a preventable disease. AB - AIMS: To determine the clinical features, management and outcome for patients admitted to hospital with tetanus in Auckland. METHODS: Medical records of all patients with tetanus admitted to hospitals in Auckland between January 1982 and December 1992 were retrospectively reviewed. RESULTS: Fifteen patients were admitted to hospital during the study period. All patients were more than 40 years old and no patient had a history of more than one tetanus toxoid immunisation before the injury presumed responsible for tetanus. Failure to consider the diagnosis led to delay in starting appropriate treatment in most patients. Eleven patients required mechanical ventilation. The median duration of hospital stay was 44 days. All patients survived. CONCLUSIONS: Tetanus is rare in Auckland and almost exclusively affects those born before 1960 when universal childhood immunisation against tetanus was started. The disease causes significant morbidity which could be avoided by increased efforts to ensure that all persons have completed a full course of immunisation. Universal vaccination against tetanus with regular boosters to maintain immunity would also circumvent the problems encountered with postexposure tetanus prophylaxis. PMID- 8202292 TI - Fluoxetine and hyponatraemia--a potential hazard in the elderly. AB - AIMS: To review reports of the association between fluoxetine and hyponatraemia. METHODS: Reports of hyponatraemia associated with fluoxetine received over a four year period in the New Zealand Intensive Medicines Monitoring Programme have been examined and these and other case reports in the literature, discussed. RESULTS: Seven patients, all women aged 68-88 years on fluoxetine 20 mg daily, developed hyponatraemia (serum sodium 114-128 mmol/L, five within 19 days of commencement of fluoxetine. The reported rate for women over 65 years was 8.5 per thousand. Withdrawal of fluoxetine was associated with recovery in all cases. CONCLUSIONS: Fluoxetine is associated with a significant incidence of hyponatraemia in the elderly, especially during the first weeks of therapy. It is advisable to monitor electrolytes in older patients during this period. PMID- 8202293 TI - Acute thoracic disc prolapse with paraparesis following a rugby tackle: a case report. PMID- 8202294 TI - The occupational overuse syndrome. PMID- 8202296 TI - New Zealand Society for the Study of Diabetes. PMID- 8202295 TI - The occupational overuse syndrome. PMID- 8202297 TI - Pool drownings. PMID- 8202298 TI - Tuberculous jejunal lymphadenitis in HIV infection. PMID- 8202299 TI - The management of rheumatoid arthritis. PMID- 8202300 TI - Treatment of erythrocytosis in a renal transplant recipient by angiotensin converting enzyme inhibition. PMID- 8202301 TI - Hysteroscopy: a review. AB - A review of the applications of hysteroscopy in obstetrics and gynecology is presented. Historical aspects, instrumentation, and media are interrelated. The respective diagnostic and therapeutic applications are reviewed separately, followed by more recent developments and potential applications. The review confirms that the hysteroscope is a necessary tool in the gynecologists armamentarium. PMID- 8202302 TI - Enterocele: a review. AB - An enterocele is a hernia of the small intestine into the vagina. First described in 1736, it is an uncommon but potentially quite symptomatic clinical entity. Despite increased interest in enterocele during the past 50 years, there are few large series reported, and follow-up on surgical results has generally been poor. Many enteroceles follow vaginal or abdominal hysterectomy. Various surgical techniques for repair of enterocele are presented herein, including the classical repairs by Ward and Moschcowitz. Because enterocele frequently coexists with vaginal vault prolapse, contemporary procedures for simultaneous repair are described. Emphasis is placed upon prophylactic vaginal vault suspension and cul de-sac obliteration at the time of abdominal or vaginal hysterectomy. The complications of failure to recognize enterocele are spontaneous vaginal evisceration, although rare, and progressive symptomatology. Attempted repair may also engender complications, some life-threatening. PMID- 8202303 TI - Ability of hydroxyapatite-bone morphogenetic (corrected from morphologenetic) protein (BMP) complex to induce dentin formation in dogs. AB - This histological investigation examined the formation and differentiation of pulp cells under the influence of HAP/BMP complex. HAP/BMP complex was implanted in exposed pulp of the mandibular premolars and alveolar bone defect in the dog. Sequential changes in these areas were examined mainly under a light microscope and partly under a scanning electron microscope. Two weeks after the operation, fibroblast-like cells proliferated right beneath the implanted complex, and after 3 weeks, dentin including dentin tubules grew in the pulp. After four weeks a dentin bridge composed of osteoid dentin was found, and after 8 weeks this dentin calcified and covered the defective surface of the root and adhered to new bone surrounding the HAP granules. The results indicated that the dentin induced by HAP/BMP complex may be of two types: tubular dentin and osteodentin. This complex exhibited outstanding ability to induce dentinogenesis and osteogenesis. PMID- 8202304 TI - Immunohistochemical detection of alkaline phosphatase in formalin-fixed and paraffin-embedded rat organs by means of avidin-biotin peroxidase complex method. AB - The author attempted the detection of alkaline phosphatase (ALP) protein in various rat organs, which were fixed with formalin and embedded in paraffin, by means of the avidin-biotin peroxidase complex (ABC) method. Reaction products were detected after a usual incubation time of 30 min at room temperature in anti ALP antibody. Positive reactions were observed in the kidney and liver but not in the small intestine, and this indicates that the antibody used in the present study reacts only with the tissue-nonspecific type of ALP. PMID- 8202305 TI - Ultrastructure of the parathyroid gland of magnesium-treated golden hamster exposed to a hypergravity environment: a stereological study. AB - The ultrastructure of the parathyroid glands of magnesium-treated golden hamsters exposed to a 5 gravity environment was studied. In the parathyroid glands of the magnesium-treated animals exposed to a hypergravity environment, the Golgi complexes and cisternae of the granular endoplasmic reticulum were increased as compared to those of the magnesium-treated animals and decreased as compared to those of animals exposed to a hypergravity environment, but were almost the same as those of the control animals. In the control and experimental animals, the chief cells were rich in free ribosomes and mitochondria. In addition, numerous secretory granules were situated close to the plasma membrane in the magnesium treated animals exposed to a hypergravity environment. These observations suggest that the synthesis of parathyroid hormone may be stimulated in the parathyroid glands of magnesium-treated hamsters exposed to hypergravity environment. PMID- 8202306 TI - Three-dimensional architecture of the subepithelial connective tissue layer in the mouse retromolar region. AB - The three-dimensional architecture of the subepithelial connective tissue layer in the mouse retromolar region was studied by scanning electron microscopy after removal of the epithelial layer. The connective tissue papillae (CTP) of the taste bud papillae (the retromolar papillae) appeared as a barnacle-like in form and had the round depression, corresponding to the site of taste bud, on their top. The CTP of the retromolar papillae and the openings of the salivary glands were concentrated collectively in the narrow zone just posterior to the molar teeth. This topographical relationship seems to reflect a physiological function; i.e., the food ground by the molar teeth is dissolved in saliva and stimulates the taste buds in the retromolar papillae. Further, the conical or cylindrical CTP were arranged around the CTP of the retromolar papillae. It is suggested that the conical or cylindrical CTP play an important role in increasing the epithelial-connective tissue interface and in resisting the excessive force during mastication. PMID- 8202307 TI - Suitable fixation condition for rat liver using microwave irradiation and its application to the immunohistochemistry of glutamate dehydrogenase. AB - The rat liver was fixed with microwave (MW) fixation technique using a domestic microwave oven and glutamate dehydrogenase (GDH) was immunostained in the liver. The structure of liver was well preserved and formation of artificial vacuoles was hardly recognizable in the cytoplasm of liver cells when 2% paraformaldehyde containing 10% glucose and 0.025% CaCl2 was employed for a fixative and continuous MW irradiation was carried out for 30 sec. Granulated immunoreaction products of GDH were present in the cytoplasm of the liver cells and Kupffer cells. The intensity of the reaction was almost homogeneous among the cells. On the other hand, when the tissue was fixed with immersion fixation method, a diffuse reaction was seen in the cytoplasm of liver cells and intensity of the immunostaining was heterogeneous among the cells; the liver cells in zone 2 showed weaker reaction than those in zone 1 and 3. Immunoelectron microscopy revealed that GDH was located in the mitochondrial matrix along the inner membrane including crystal membrane. PMID- 8202308 TI - Double left renal veins and multiple right renal veins found in Japanese adults. AB - A case of circumaortic renal venous collar, the first such collar to be observed in a Japanese female cadaver, is presented, and its anatomical organization is compared with that in another case in which four right renal veins accompanied four right and three left renal arteries in a Japanese male cadaver. Double left renal veins are formed by persistence of a more central retroaortic venous anastomosis, in contrast to multiple right renal veins, which are formed by persistence of some embryonic renal veins arranged in ladder-like patterns. In our case, the dorsal limb of the renal collar communicated with the azygos system veins and lumbar veins. The azygos system veins were considered to have atrophied as a result of some persisting retroaortic venous anastomoses located in the thorax. Therefore, we believe that the renal collar was related to the atrophy of the azygos system veins. To determine whether there are racial differences in incidence of renal collar, further studies in Asians are required. PMID- 8202309 TI - Cochlear synaptic development and morphology in a genetically induced type of progressive hair cell degeneration. AB - In mice with genetically induced inner ear abnormalities it is conceivable that in the morphogenetic types and in mutants with the spotting kind of pigmentary anomaly, the genes act through the developing nervous system. It has been suggested that in degenerative (neuroepithelial) mutants the influence of the gene is also reflected in the inner ear through the agency of the nervous system. The jerker mouse belongs to the neuroepithelial type of mutants which in homozygotes results in early postnatal degeneration of the sensory epithelium of the inner ear, initially confined to the cuticular plate and the stereocilia. In spite of well-advanced hair cell degeneration, these mutants developed morphologically normal afferent and efferent nerve terminals at cochlear hair cells. PMID- 8202310 TI - Evidence of measles virus RNA in otosclerotic tissue. AB - By use of the very sensitive polymerase chain reaction technique, evidence is given that otosclerosis is a measles-virus-associated disease of the otic capsule. These results support recent observations which demonstrated the expression of measles antigen within active otosclerotic foci by immunohistochemical methods. Thus it is hypothesized that the viral infection acts as at least one pathogenetic factor during the development of this obscure, locally restricted inflammatory bone disease. PMID- 8202311 TI - Electrocochleography in deaf subjects. AB - Electrocochleography using the transtympanic electrode technique was performed on 86 deaf ears. Auditory nerve action potential was detected in 9 ears, in 5 of which deafness was caused by cerebellopontine angle tumor or surgery. A low threshold of the cochlear microphonics' response was also observed in some of the cases with deafness caused by mumps or cerebellopontine angle tumor. Various pathophysiological states of the inner ear can be observed, even in cases showing the same total deafness when measured by audiometer. PMID- 8202313 TI - Bony anatomy of the anterior epitympanic space. AB - The anatomy of the anterior epitympanic space is complex and relatively unfamiliar to the surgeon. The size of the space is unpredictable. From the surgeon's perspective, we studied the bony anatomy of the anterior epitympanic space in 35 cadavers. There was an impressive variability of bony openness into the anterior mesotympanum; the openness was bilaterally symmetrical. As a potential auxiliary ventilation route for the epitympanum of the chronic otitis patient, each specimen was found to have sufficient room to surgically establish a route at least 2 mm in diameter to connect with the anterior mesotympanum. None of the specimens had dehiscent facial nerve in the anterior epitympanic space, but 60% of specimens had dehiscent facial nerve adjacent to the stapes. The anatomic variations of the anterior epitympanic space were not related to prior otitis media. Three fourths of the medial walls of the anterior epitympanic spaces lacked the bony trabeculae that are otherwise typical of the epitympanum. Because the medial wall contours were bilaterally symmetrical, because the contours were unassociated with indicators of prior otitis media, and because of apparent contour differences in Orientals and Caucasians, a congenital factor is suggested to determine the contour of the medial wall of the anterior epitympanic space. PMID- 8202312 TI - Cytochemical study of ouabain-sensitive, K(+)-dependent p-nitrophenylphosphatase activity in guinea pig facial nerve. AB - The localization of ouabain-sensitive, K(+)-dependent p-nitrophenylphosphatase (K NPPase) activity, the second dephosphorylative property of the Na-K adenosine triphosphatase complex, was cytochemically studied in the intra-temporal portion of the facial nerve in normal guinea pigs using a cerium-based method. A fine granular reaction product of the K-NPPase activity was observed on the cytoplasmic side of the axolemma of the axon cylinder, of the incisures of Schmidt-Lanterman, and of the nodes of Ranvier. No reaction product was detected on the periaxonal and outermost plasma membrane of Schwann cells and in the myelin sheath. In control tissue samples, the enzyme activity was almost completely inhibited by 10 mM ouabain, and no reaction was noted in medium without K+. PMID- 8202314 TI - Sex steroid receptors in papilloma, normal mucosa and polyps of the nose. AB - Sex steroid hormone receptors (SSHR) were determined in 14 cases of sinonasal papillomas, 17 cases of nasal polyps and in the normal nasal mucosa of 13 patients. The determination of SSHR was done by the dextran-coated charcoal assay from cytosol protein. All the cases of sinonasal papilloma were SSHR negative, while some specimens of normal nasal mucosa contained small amounts of SSHR. In addition, some cases of nasal polyps were found to contain low concentrations of the receptors, but concentrations were lower than those found in normal mucosa. Although nasal papillomas are more common in men than in women, this study shows that SSHR do not play any role in the development of these tumors. PMID- 8202315 TI - Statistical analysis of malignant tumors detected as the cause of vocal cord paralysis. AB - It is well known that vocal cord paralysis is sometimes the only sign of an otherwise symptom-free malignant tumor. We report 69 cases of vocal cord paralysis caused by malignant tumor experienced at our clinic over the past 18 years. They consisted of 28 cases of thyroid cancer, 21 lung cancer, 14 esophageal cancer, 3 mediastinal tumors and 3 tumors of miscellaneous origin: 41 cases were male and 28 female. In the 65 patients with unilateral paralysis, the left side was affected in 45 and the right in 20. The remaining 4 patients had bilateral paralysis. There was a marked sex difference in the origin of malignant tumors; the incidence of lung cancer was higher in males with paralysis on the left side, while that of thyroid cancer was higher in females. Ultrasonography (US) of the neck, chest X-ray, CT scan of the chest and contrast esophagography should be performed for the detection of malignant tumors in cases with left paralysis, while US of the neck and chest X-ray appear to be sufficient in cases of right paralysis. PMID- 8202316 TI - A case report of Sjogren's syndrome with repeated false cord swelling. AB - We present a 42-year-old female patient who had repeated swelling of the bilateral false cords. The patient complained of dryness of the eyes and oral mucosa, and was diagnosed as having Sjogren's syndrome. She underwent partial resections of the bilateral false cords 4 times in 3 years to evaluate the nature of the disease and to relieve airway obstruction. Histologic examinations revealed severe atrophic changes of the laryngeal glands and cystic dilation of the ducts of the glands, associated with marked lymphocytic infiltration and lymphoid hyperplasia. These findings suggest that the etiology of the swelling of the false cords was related to Sjogren's syndrome. PMID- 8202317 TI - Multiple symmetrical lipomatosis: no longer just a Mediterranean disease? AB - Multiple symmetrical lipomatosis is a rare condition, of which the etiology remains unclear. Most reported cases have been from the Mediterranean countries, and it is generally thought of as a disorder characteristic of that region. However, there have been 11 cases reported in Japan since 1978, suggesting that this condition is no longer confined to Mediterranean countries. PMID- 8202319 TI - [Partial monosomy 21 or fetal alcohol embryopathy in a retarded boy?]. AB - A male newborn showed dysmorphisms combined with a complex cerebral malformation and a growth retardation. Alcohol damage in utero was suspected to be the cause. A deletion 21q (mosaic) was found in the karyotype. PMID- 8202318 TI - [Techniques and clinical application of capnography in newborn infants and infants]. AB - Capnography has not yet achieved wide application as a noninvasive method for monitoring and optimizing assisted ventilation in neonatological intensive care medicine. The development of new equipment will probably make it possible for capnography to find its place as a routine examination. The aim of this work is to evaluate the existing methods for CO2-analysis in newborns and infants using data from existing literature. A mainstream capnograph (Novametrix 7000) was used to demonstrate typical capnographic curves in newborns and prematurely born children. The results offer new possibilities for the optimization of assisted ventilation. PMID- 8202320 TI - [Diagnosis of hearing disorders in premature infants]. AB - In cases of severe hearing loss in babies an early rehabilitation should prevent a delay in development. More than a half of all hearing disorders in children are acquired; to a large extend these hearing disorders are caused by premature birth and can be detected by suitable screening. Two methods are used for testing: (1) reflex audiometry with a standardized stimulus generator; and (2) bedside recording of brainstem potentials. Having tested the method of bedside recording of brainstem potentials a group of 60 premature infants of varied body weights and no additional diseases was examined as "normal" control group. Only premature birth with all signs of maturation adequate for gestational age is not a greater risk for hearing disorders. In premature infants with birth weights less than 1500 g, having marked hyperbilirubinemia and extensive intracranial bleeding always increased wave V latencies has been observed. In about 10% of these children severe hearing disorders were diagnosed and after leaving the premature department were sent to a paedaudiological dispensaire. PMID- 8202321 TI - Effectiveness of sensory integration therapy on smooth pursuits and organization time in children. AB - In this study the effect of sensory integration (SI) therapy on smooth pursuit eye movements, tracking and learning time was evaluated in 21 children diagnosed with sensory integration dysfunction. A control group of 11 normal children, matched for age and sex was also tested. Electrooculograph (EOG) recordings were inspected for number of saccadic intrusions during smooth pursuit movements. Prior to therapy the children in the SI treatment group exhibited significantly more saccadic intrusions during smooth pursuit movements and took significantly longer to perform the task than the normal control group. After 6-9 months of SI therapy one hour a week, there was a significant reduction in the number of saccades in the treatment group. The treatment group demonstrated a reduction in the time necessary to accomplish smooth pursuits and organizational time. The etiology of these improvements may be related to the subcortical substrated utilized in SI therapy as well as in the generation of smooth pursuit eye movements. PMID- 8202322 TI - [Aarskog syndrome in association with mental and psychological retardation, grand mal epilepsy and tardive dyskinesia and apparent radicular paralysis of the fibular nerve in torsion scoliosis]. AB - The case of an about 22-year-old patient with AARSKOG-syndrome is reported whose scoliosis caused a radicular impairment with resulting severe paresis of the right fibular nerve. The syndrome was also associated with moderate mental retardation, epilepsy, premature craniosynostosis and tardive dyskinesias after neuroleptic therapy because of disorders of behaviour. The risks of idiopathic scoliosis in patients with dysmorphia-retardation syndromes should be taken into consideration and such children should be supervised by an orthopaedist. PMID- 8202323 TI - [Trends in treatment statistics and results in hematology/oncology at the Rostock University Pediatric Clinic. Exemplified especially with reference to leukemia and lymphogranulomatosis]. AB - The article presents a report about the work over 20 years (in the seventies and eighties) of the Rostock pediatric oncologic-hematologic treatment center in the field of the diagnoses leukemia and lymphogranulomatosis. The author describes newer aspects of ward care, out-patient care and care limited to a few hours at the day-care ward for the ill children and their parents. One resulting aspect is the importance of psycho-social and rehabilitative guidance for periods of time. PMID- 8202324 TI - [Television behavior of a pediatric and adolescent psychiatric patient population]. AB - Television viewing is a common phenomen influencing everyday life of children. A questionnaire on the use of television was administered to 97 children aged from 5 to 19 years, and their parents. On an average, children spend 2 to 5 hours daily viewing television. Their parents accept this amount of time. Adolescents watch more TV than younger children. The social background was not related to the amount of time spent viewing television. Children with behavior disorders (F90 92) spend the same time watching television like children without behavior problems. 1/3 of the children owned their own television set using it more often. Nearly 50% like programs with violent and aggressive themes. PMID- 8202325 TI - [News from allied medical fields. Medical genetics. DNA fingerprinting: procedures and applications]. PMID- 8202326 TI - [News from allied medical fields. Medical genetics. Possibilities of computer assisted phenotype diagnosis in human genetic counseling]. PMID- 8202327 TI - [News from allied medical fields. Medical genetics. Legal problems in genetic analysis and human genetic counseling]. PMID- 8202328 TI - Prediabetes: genetic, immunological and metabolical aspects. AB - There is mounting evidence from experimental animal diabetes and from human epidemiological studies that a long period of "prediabetes" precedes the clinical onset of type 1 (Insulin Dependent) Diabetes Mellitus. In this review, the authors evaluate the main informations concerning the genetic, immunological and metabolic aspects of this phase of prediabetes and the relationship of prediabetes with the onset of the disease. Prediabetes is a long period; in this period the destruction of beta cells can be caused by many factors and by many pathogenetic mechanisms. Nowadays, we begin to understand some of these mechanisms and the central role of the activation of the immune system; this activation results in various humoral and cellular abnormalities detectable in the prediabetic phase. These abnormalities, together with metabolic ones, have been reported in many studies. Consequently, we have at our disposal some genetic, immunological and metabolical markers which can be useful in the detection of the person at risk of developing diabetes mellitus. PMID- 8202329 TI - Multiple tumour markers for diagnosis, management and follow-up of potentially resectable lung cancer. AB - The present prospective study has been carried out to evaluate the role of tumour markers in the preoperative assessment and follow-up of patients with potentially resectable lung cancer. The carcinoembryonic antigen (CEA), neuron specific enolase (NSE), and tissue polypeptide antigen (TPA) have been preoperatively measured in 133 lung cancer patients and in 75 healthy smokers. The same tumour markers have been serially determined during the 12 to 30 month-follow-up of 53 subjects who had a complete resection. In screening for localized lung cancer, TPA determination was the single most accurate diagnostic test. The combined measurement of several tumour markers did not result in a greater diagnostic accuracy of the assay. In predicting lung cancer unresectability, CEA, though being the most suitable test, allowed preoperative detection of only one third of patients with unremovable tumours. In monitoring the postresectional course of subjects who had a complete resection, the combined measurement of TPA and NSE proved to be a very reliable predictor of disease recurrence. PMID- 8202330 TI - Antineoblastic activity of antioxidant vitamins: the role of folic acid in the prevention of cervical dysplasia. AB - The authors made a study on 90 patients affected by various degrees of uterine cervix dysplasia searching for folic acid plasmatic concentrations. The team members affected by CIN have been compared with a test team consisting of women with normal pap-test and vaginoscopy. The study proved that the average levels of folic acids have significantly decreased in cases of dysplasia compared with the test team. These results allow stating that low folic acid plasmatic concentrations may be associated with cervix neoplasms development. PMID- 8202331 TI - An objective evaluation of retrocochlear function by means of CNT (Cochlear Nerve Tester). AB - Indications for hearing implants in profoundly deaf patients have been presented. Auditory pathway status was evaluated by application of electric stimulation of cochlear nerve. The electric stimulus originated from Cochlear Nerve Tester. Obtained sound sensations might be revealed on ABR pattern. PMID- 8202332 TI - Cutaneous, musculoskeletal and bone flow scintiscan by intravenous infusion of 99mTc-MDP (Diphosphonate) in the evaluation and control of patients treated with spinal cord stimulation for ischaemic pain. AB - In patients affected by unbearable pain secondary to peripheral vascular disorders beyond surgical repair such as thromboangitis obliterans, diabetic microangiopathy, arteriosclerosis obliterans, there is a need to establish the degree of micro-circulation functionality before proceeding with invasive pain therapy, such as Spinal Cord Stimulation (SCS). From our series some cases of refractory ischaemic pain subjected to nuclear medicine techniques assessment before and after SCS implant will be presented; these data suggest that the use of radionuclides for quantifying regional perfusion, in view of the information it offers us both in the dynamic angiographic phase and in the later static phase, constitutes a very valid aid in the diagnosis and treatment of chronic pain conditions of ischaemic origin. Cutaneous, musculoskeletal and bone flow scintiscan is a non-invasive procedure which allowed us to make an objective selection of patients who are candidates for prolonged conservative treatment thus limiting the incidence of ineffective permanent SCS implants. PMID- 8202333 TI - Epidemiology of atrial fibrillation in patients hospitalized in a large hospital. AB - The prevalence of atrial fibrillation varies widely depending on the population studied. To understand the incidence of atrial fibrillation and its significance in relation to other diseases, 3 years (1989 through 1991) of consecutive hospital discharges from the neurology and internal medicine services at Henry Ford Hospital were studied. Of the 26,964 patients who qualified for analysis, 1346 (5%) had atrial fibrillation as 1 of their 5 recorded discharge diagnoses. Comparing the group without atrial fibrillation to those with atrial fibrillation, there were 51% males in both groups (p = 0.88). African-Americans comprised 33% of the patients with atrial fibrillation and 50% of the patients without atrial fibrillation (p < 0.001). The average age of those with atrial fibrillation was 72 +/- 13 years, and 58 +/- 18 years for those without atrial fibrillation (p < 0.001). Length of hospital stay was 9.6 +/- 8.6 days with atrial fibrillation and 7.6 +/- 9.2 days for those without atrial fibrillation (p < 0.001). After adjusting for the effects of age, significant positive associations were noted in those patients with atrial fibrillation whose co existing condition was either stroke, heart failure, myocardial infarction, hyperthyroidism, or mitral valve disease. There was also a significant negative relationship between hypertension and atrial fibrillation. The most common of the 5 discharge diagnoses observed in patients with atrial fibrillation was congestive heart failure (40%), followed by hypertension (23%) and ischemic heart disease (21%). The existence of a comorbid disease in patients with atrial fibrillation is important, as it can influence medical management and prognosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202334 TI - Naltrexone must not be considered a real therapy in functional hypothalamic amenorrhea. The results of a double blind controlled study. AB - Endogenous opioids exert a tonic inhibitory control on GnRH pulsatility at the hypothalamic level and it must be responsible for some hypogonadotropic hypogonadic syndromes such as functional hypothalamic amenorrhea (FHA). We treated 22 patients suffering from FHA with an oral anti-opioid drug, Naltrexone Hydrochloridrate (NH), 50 mg once a day or placebo, in a double blind controlled study. Six patients exhibited a regular resumption of their menstrual cycles (4 on placebo and only 2 on NH). There was an increase of 17BE2 in 3 of these 6 patients; progesterone levels did not change at all. Gynaecological echography demonstrated folliculogenesis in 4 of these 6 patients (only 1 on NH). The results show that NH is not a real therapy in patients suffering from FHA. Furthermore placebo, useful to the resumption of menstrual bleeding in 4 patients, underlines the importance of psychosomatic effects in the therapeutic management of FHA. PMID- 8202335 TI - Thymostimulin effect on the immune response in neoplastic patients submitted to surgical treatment. AB - We selected the data from performance status, disease state, skin tests, circulating lymphocytes and relative subsets, serum immunoglobulin classes to evaluate the immune response in 29 neoplastic patients treated with surgery and undergoing Thymostimulin administration during long term follow-up. Moderate drug intolerance was observed in 3 patients. After treatment lymphocyte count increase (41% mean increase) in 61.5% of cases; CD3, CD4, CD8, CD16 respectively 95-74-87 82% of cases; immunoglobulin classes in about 90% of cases. A clear-cut improvement of Karnofsky's index was observed in 34.6% of cases, worsening in 11.5%. A manifest improvement in the delayed hypersensitivity skin test resulted in 36% of cases. Most patients (85%) have shown signs of complete disease remission. Disease progression was observed only in 3 patients. There were no infections during this study. PMID- 8202336 TI - Thymostimulin effect on the immune response in pulmonary carcinoma with or without surgical treatment. AB - Experience with 54 patients affected by pulmonary carcinoma treated or not with surgery and undergoing thymostimulin administration during long-term follow-up (70 mg i.m. every other day for 3 months), is reported. Drug intolerance was observed in 5.5% of cases. In patients who were able to complete the therapeutic cycle (50 cases) objective improvement of Performance Status was obtained in 46% of cases and subjective improvement in nearly 90%. The course of neoplastic disease showed definite progression (presence of local recurrence or distant metastasis) in 20% of cases, remission in 6%. No case of onset of pulmonary or extrapulmonary infections was observed. After treatment, a significant increase (between 24% and 108%) in blood parameters (circulation lymphocytes, CD3, CD4, CD8, CD16, IgG, IgA, IgM) was observed in 28-56% of cases. As for CD4 increase, this was accompanied by concomitantly positive Merieaux test in 44.5% of cases. Quiescence or complete remission has appeared to occur together with high CD16 values, progression with high CD8 and low CD16 values. PMID- 8202337 TI - Danazol in the treatment of endometrial hyperplasia. AB - The paper reports the results of a study performed in 62 menorrhagic women with endometrial hyperplasia treated with Danazol. The efficacy and tolerability of the above drug was found to be satisfactory. PMID- 8202338 TI - Our operative technique for inguinal hernia. AB - The most commonly used methods of hernia repair are either Bassini repair or modifications of Bassini repair in fact each sutures, with different methods, the three anatomical coats (transversalis fascia, transversus abdominis and internal oblique muscles, external oblique muscle aponeuroses). Here we propose a different operative technique that sutures only two aponeurotic coats (transversalis fascia and over external oblique muscle aponeuroses). The second sutured coat supports the posterior wall of the inguinal canal. Between 1984 and 1989 we operated about 1100 patients with this method and the recurrence rate is in accordance with the incidence of the other usual types of hernia repair. PMID- 8202339 TI - Use of a metal detector in the search for bullets during autopsy. AB - The paper reports the results obtained from the use of a CEIA PD 140 S metal detector to search for bullets during the course of medicolegal tests. The instrument was found to be of value in identifying their presence up to a distance of 5-7.5 cm from the sensitive detection area. PMID- 8202341 TI - Puzzles in longevity. PMID- 8202340 TI - How clinical observations of a congenital disease can be translated in terms of molecular biology. PMID- 8202342 TI - Searching for the neural correlates of associative structures. PMID- 8202343 TI - A history of the reaction between oxaloacetate and acetate for citrate biosynthesis: an unsung contribution to the tricarboxylic acid cycle. PMID- 8202344 TI - Gene frequencies, DNA sequences, and human origins. PMID- 8202345 TI - Scientific status of aromatherapy. PMID- 8202347 TI - Some effects of group drug taking. PMID- 8202346 TI - Surgeons' quest for life: the history and the future of xenotransplantation. PMID- 8202348 TI - The American medical doctor in the current milieu: a matter of trust. PMID- 8202350 TI - The RFC2 gene encoding a subunit of replication factor C of Saccharomyces cerevisiae. AB - Replication Factor C (RF-C) of Saccharomyces cerevisiae is a complex that consists of several different polypeptides ranging from 120- to 37 kDa (Yoder and Burgers, 1991; Fien and Stillman, 1992), similar to human RF-C. We have isolated a gene, RFC2, that appears to be a component of the yeast RF-C. The RFC2 gene is located on chromosome X of S. cerevisiae and is essential for cell growth. Disruption of the RFC2 gene led to a dumbbell-shaped terminal morphology, common to mutants having a defect in chromosomal DNA replication. The steady-state levels of RFC2 mRNA fluctuated less during the cell cycle than other genes involved in DNA replication. Nucleotide sequence of the gene revealed an open reading frame corresponding to a polypeptide with a calculated Mr of 39,716 and a high degree of amino acid sequence homology to the 37-kDa subunit of human RF-C. Polyclonal antibodies against bacterially expressed Rfc2 protein specifically reduced RF-C activity in the RF-C-dependent reaction catalyzed by yeast DNA polymerase III. Furthermore, the Rfc2 protein was copurified with RF-C activity throughout RF-C purification. These results strongly suggest that the RFC2 gene product is a component of yeast RF-C. The bacterially expressed Rfc2 protein preferentially bound to primed single-strand DNA and weakly to ATP. PMID- 8202351 TI - Pokeweed antiviral protein (PAP) mutations which permit E.coli growth do not eliminate catalytic activity towards prokaryotic ribosomes. AB - Pokeweed antiviral protein (PAP) has N-glycosidase activity towards both eukaryotic and prokaryotic ribosomes. This is in marked contrast with the A chains of type 2 ribosome inactivating proteins (RIPs) such as ricin and abrin, which inactivate only eukaryotic ribosomes. A recent report described spontaneous mutations in PAP that implicated specific amino acids to be involved in determining the activity of PAP towards prokaryotic ribosomes. As part of an ongoing study into RIP--ribosome interactions these mutations were specifically recreated in a PAP clone encoding the mature 262 amino acid PAP sequence. Mutants were tested for their N-glycosidase activity by analysing the integrity of eukaryotic and prokaryotic ribosomes after mutant protein expression. Mutations of F196Y and K211R, either individually or within the same clone, were active toward both classes of ribosome, indicating that these amino acid positions are not involved in differentiating ribosomal substrates. Mutation R68G led to a protein that appeared to be inactive towards prokaryotic ribosomes, but also very poorly active towards eukaryotic ribosomes. This mutation is currently under further investigation. PMID- 8202349 TI - A sequence compilation and comparison of exons that are alternatively spliced in neurons. AB - Alternative splicing is an important regulatory mechanism to create protein diversity. In order to elucidate possible regulatory elements common to neuron specific exons, we created and statistically analysed a database of exons that are alternatively spliced in neurons. The splice site comparison of alternatively and constitutively spliced exons reveals that some, but not all alternatively spliced exons have splice sites deviating from the consensus sequence, implying diverse patterns of regulation. The deviation from the consensus is most evident at the -3 position of the 3' splice site and the +4 and -3 position of the 5' splice site. The nucleotide composition of alternatively and constitutively spliced exons is different, with alternatively spliced exons being more AU rich. We performed overlapping k-tuple analysis to identify common motifs. We found that alternatively and constitutively spliced exons differ in the frequency of several trinucleotides that cannot be explained by the amino acid composition and may be important for splicing regulation. PMID- 8202352 TI - A simple method for detecting single base substitutions and its application to HLA-DPB1 typing. AB - We have developed a simple and reliable method, PCR-PHFA (polymerase chain reaction dependent preferential homoduplex formation assay), for detection of single base substitutions within PCR amplicons. This technique is based upon strand competition during hybridization between a double labeled amplicon, prepared from biotin and DNP labeled primers, and an unlabeled amplicon. Under the precisely controlled temperature gradient, the preferential formation of a homoduplex over a heteroduplex occurs. After annealing, the identical sequence of the double labeled and unlabeled amplicon resulted in a low population of regenerated double labeled dsDNA due to strand exchange between them. Even when the two differed by only a single base substitution, double labeled molecule was regenerated efficiently because of preferential homoduplex formation. The regenerated double labeled molecule was captured onto a streptavidin coated microtiter plate and quantified enzymatically with a chromogenic substrate. The technique has been successfully applied in HLA-DPB1 typing. Furthermore, we detected a mutated gene even in the presence of a large excess of the corresponding normal gene. PMID- 8202353 TI - Formation of the yeast splicing complex A1 and association of the splicing factor PRP19 with the pre-mRNA are independent of the 3' region of the intron. AB - Assembly of the spliceosome is a step-wise process and involves sequential binding of snRNAs to the pre-mRNA to form pre-splicing complex A2-1. Subsequent dissociation of U4 from the spliceosome is accompanied by formation of complex A1 (Genes Dev. 1, 1014-1027, 1987). We show that the 3' region of the intron sequence is not required for efficient assembly of the yeast spliceosome. Truncated precursor mRNA retaining only four or five nucleotides 3' to the TACTAAC box formed pre-splicing complex A1, kinetically the last pre-mRNA containing splicing complex identified. The subsequent cleavage--ligation reaction requires at least 23 nucleotides on the 3' side of the TACTAAC box in a sequence-independent manner. Immunoprecipitation with anti-PRP19 antibody showed that association of PRP19 with the spliceosome was also independent of the 3' region of the intron. PMID- 8202354 TI - Intramolecular signal transduction within the FixJ transcriptional activator: in vitro evidence for the inhibitory effect of the phosphorylatable regulatory domain. AB - FixJ is a phosphorylatable 'response regulator' controlling the transcription of the key nitrogen fixation genes nifA and fixK in Rhizobium meliloti. Sequence and genetic analyses indicated that FixJ comprises an N-terminal phosphorylatable regulatory domain, FixJN, and a C-terminal transcriptional activator domain, FixJC. We have now overexpressed and purified the FixJC protein and show that it is fully active in an in vitro transcription system with purified RNA polymerase. FixJC appeared to act synergistically with RNA polymerase at the nifA promoter. Furthermore FixJC was more active in vitro than the full-length dephosphorylated FixJ protein. Therefore activity of FixJC is inhibited by FixJN within the FixJ protein. This inhibition is relieved by phosphorylation of FixJN. Such a negative mode of intramolecular signal transduction may be generalizable to other response regulators. PMID- 8202355 TI - Oligo[d(C).(G)] runs exhibit a helical repeat of 11.1 bp in solution and cause slight DNA curvature when properly phased. AB - We have inserted d(C)10 in a set of DNA fragments with bent segments on both ends, which are rotated with respect to each other by base pair wise increasing insertions. The electrophoretic mobilities on polyacrylamide gels of these DNA fragments were used to identify insertion sizes with cis conformations of the bent ends. These experiments revealed a helical repeat in solution of d(C).d(G) tracts of 11.1 +/- 0.08 bp. The electrophoretic mobilities of ligation ladders with properly phased d(C)5 and d(C)16 runs demonstrate a small but clearly detectable curvature of these fragments. PMID- 8202356 TI - Evidence for a conformational change in the DNA gyrase-DNA complex from hydroxyl radical footprinting. AB - We have used the technique of hydroxyl radical footprinting to probe the complex between DNA gyrase and a 198 bp DNA fragment containing the preferred gyrase cleavage site from plasmid pBR322. We find that gyrase protects 128 bp from the hydroxyl radical with the central 13 bp (adjacent to the gyrase cleavage site) being most strongly protected. Flanking the central region are arms showing periodic protection from the reagent suggesting a helical repeat of 10.6 bp, consistent with the DNA being wrapped upon the enzyme surface. The presence of 5' adenylyl-beta,gamma-imidodiphosphate or a quinolone drug causes alteration of the protection pattern consistent with a conformational change in the complex involving one arm of the wrapped DNA. The significance of these results for the mechanism of DNA supercoiling by gyrase is discussed. PMID- 8202357 TI - Activation of the immunoglobulin kappa 3' enhancer in pre-B cells correlates with the suppression of a nuclear factor binding to a sequence flanking the active core. AB - Both the kappa intron and the kappa 3' enhancer are required for high levels of immunoglobulin kappa gene expression. The activity of both enhancer elements can be induced by LPS in pre-B cells. While the LPS induction of the kappa intron enhancer is mediated by NF-kappa B, this factor is not responsible for activation of the 3' enhancer. Dissection of the 3' enhancer has shown that in pre-B cells the activity of the kappa 3' enhancer is repressed by a region flanking an active core element. We have now scanned this flanking region for nuclear factor binding sites and have identified sites for B-cell specific E47/E12-like proteins and two ubiquitous nuclear proteins. Furthermore, we have identified a nuclear factor in pre-B cells whose binding activity is suppressed in response to LPS. In its tissue-distribution and binding specificity this factor appears to be identical to the lymphoid specific protein LEF-1. The position of the LEF-1 binding site within the 3' enhancer and its response to LPS raise the possibility that LEF-1 may be the target for a second pathway able to mediate LPS induction of immunoglobulin kappa gene transcription. PMID- 8202358 TI - Codon cassette mutagenesis: a general method to insert or replace individual codons by using universal mutagenic cassettes. AB - We describe codon cassette mutagenesis, a simple method of mutagenesis that uses universal mutagenic cassettes to deposit single codons at specific sites in double-stranded DNA. A target molecule is first constructed that contains a blunt, double-strand break at the site targeted for mutagenesis. A double stranded mutagenic codon cassette is then inserted at the target site. Each mutagenic codon cassette contains a three base pair direct terminal repeat and two head-to-head recognition sequences for the restriction endonuclease Sapl, an enzyme that cleaves outside of its recognition sequence. The intermediate molecule containing the mutagenic cassette is then digested with Sapl, thereby removing most of the mutagenic cassette, leaving only a three base cohesive overhang that is ligated to generate the final insertion or substitution mutation. A general method for constructing blunt-end target molecules suitable for this approach is also described. Because the mutagenic cassette is excised during this procedure and alters the target only by introducing the desired mutation, the same cassette can be used to introduce a particular codon at all target sites. Each cassette can deposit two different codons, depending on the orientation in which it is inserted into the target molecule. Therefore, a series of eleven cassettes is sufficient to insert all possible amino acids at any constructed target site. Thus codon cassettes are 'off-the-shelf' reagents, and this methodology should be a particularly useful and inexpensive approach for subjecting multiple different positions in a protein sequence to saturation mutagenesis. PMID- 8202359 TI - Intramolecular folding of a fragment of the cytosine-rich strand of telomeric DNA into an i-motif. AB - In the recently discovered i-motif, four stretches of cytosine form two parallel stranded duplexes whose C.C+ base pairs are fully intercalated. The i-motif may be recognized by characteristic Overhauser cross-peaks of the proton NMR spectrum, reflecting short H1'-H1' distances across the minor groove, and short internucleotide amino-proton-H2'/H2" across the major groove. We report the observation of such cross-peaks in the spectra of a fragment of the C-rich telomeric strand of vertebrates, d[CCCTAA]3CCC. The spectra also demonstrate that the cytosines are base-paired and that proton exchange is very slow, as reported previously for the i-motif. From UV absorbance and gel chromatography measurements, we assign these properties to an i-motif which includes all or nearly all the cytosines, and which is formed by intramolecular folding at slightly acid or neutral pH. A fragment of telomeric DNA of Tetrahymena, d[CCCCAA]3CCCC, has the same properties. Hence four consecutive C stretches of a C-rich telomeric strand can fold into an i-motif. Hypothetically, this could occur in vivo. PMID- 8202360 TI - Specificities of human, rat and E. coli O6-methylguanine-DNA methyltransferases towards the repair of O6-methyl and O6-ethylguanine in DNA. AB - The behaviour of highly purified bacterial expressed rat O6-methylguanine-DNA methyltransferase (MGMT) towards the repair of CGCm6GAGCTCGCG and CGCe6GAGCTCGCG (km6G/ke6G = 1.45, where k is the second order repair rate constant determined, m6G and e6G are O6-methyl and O6-ethylguanine) is similar to that of E. coli 39kD Ada protein (km6G/ke6G = 1.6). However, the human MGMT is very different (km6G/ke6G = 163). The preferential repair of O6-ethylguanine lesion by the rat MGMT appears not to be related to the lack of the initiator methionine in the expressed protein since similar results were obtained from N-terminal Glutathione S-transferase (GST) fused protein (GSTMGMT) which retains the methionine. The possible relationship between these findings and the differences observed in the primary amino acid sequence of these proteins is discussed. In addition the preferential repair of O6-ethylguanine substrate by the 39kD Ada protein as compared to the catalytic C-terminus alone (different by 134 times) suggests that the N-terminus plays a crucial role in the repair of O6-ethylguanine. This is in contrast to the minor effects of the GST domain when fused to the N-terminus of mammalian MGMT. PMID- 8202361 TI - Probing the hammerhead ribozyme structure with ribonucleases. AB - Susceptibility to RNase digestion has been used to probe the conformation of the hammerhead ribozyme structure prepared from chemically synthesised RNAs. Less than about 1.5% of the total sample was digested to obtain a profile of RNase digestion sites. The observed digestion profiles confirmed the predicted base paired secondary structure for the hammerhead. Digestion profiles of both cis and trans hammerhead structures were nearly identical which indicated that the structural interactions leading to self-cleavage were similar for both systems. Furthermore, the presence or absence of Mg2+ did not affect the RNase digestion profiles, thus indicating that Mg2+ did not modify the hammerhead structure significantly to induce self-cleavage. The base-paired stems I and II in the hammerhead structure were stable whereas stem III, which was susceptible to digestion, appeared to be an unstable region. The single strand domains separating the stems were susceptible to digestion with the exception of sites adjacent to guanosines; GL2.1 in the stem II loop and G12 in the conserved GAAAC sequence, which separates stems II and III. The absence of digestion at GL2.1 in the stem II hairpin loop of the hammerhead complex was maintained in uncomplexed ribozyme and in short oligonucleotides containing only the stem II hairpin region. In contrast, the G12 site became susceptible when the ribozyme was not complexed with its substrate. Overall the results are consistent with the role of Mg2+ in the hammerhead self-cleavage reaction being catalytic and not structural. PMID- 8202362 TI - An activity gel assay for the detection of DNA helicases and nucleases from cell free extracts. AB - An activity gel assay was developed for the detection of DNA helicases in crude extracts. The assay was based on the ability of DNA helicases to unwind radioactive fragments from single-stranded M13 circles that were immobilized in an SDS polyacrylamide gel. The displaced radioactive strands were detected by blotting them to a filter and visualizing the resulting bands by autoradiography. Experiments with purified proteins demonstrated that DNA helicases, endonucleases and exonucleases could produce activity bands. A one-dimensional gel assay was sufficiently sensitive to allow detection of DNA helicase I, DNA helicase II, DNA helicase IV, the RecQ helicase as well as 3 unidentified putative DNA helicases in crude extracts of Escherichia coli. Exonuclease and endonuclease activities from crude extracts could be distinguished from DNA helicase activities by their ATP-independence and from each other by their band morphologies. PMID- 8202363 TI - Heteroduplex molecules formed between allelic sequences cause nonparental RAPD bands. AB - Primers (10-mers) of random sequence were used to amplify RAPD bands from genomic DNA of an F1 strain of flax rust (Melampsora lini) and its two parent strains. One primer out of 160 tested was unusual in that it amplified a product from F1 DNA that was not amplified from either parental DNAs. The same primer also generated two RAPD bands that segregated as codominant alleles amongst F2 progeny. The nonparental band was only generated from DNAs of F2 individuals that were heterozygous for these two allelic sequences. Sequence analysis of the two RAPD alleles demonstrated greater than 99% sequence identity, although the larger allele possessed an additional 38bp relative to the smaller. Mixing of the two allelic sequences followed by denaturation and annealing in the absence of polymerase activity resulted in the formation of the nonparental band. Thus the nonparental band present in some RAPD reactions consisted of a heteroduplex molecule formed between two allelic sequences of different size. These data demonstrate that heteroduplex molecules formed between allelic RAPD products are a potential source of artifactual polymorphism that can arise during RAPD analysis. PMID- 8202365 TI - Heat shock-induced repression of proteolysis: poly(A)-binding protein degradation patterns can illusorily suggest its specific loss during heat shock. AB - Poly(A)-binding protein (PABP) is highly susceptible to proteolysis during cell lysis of Drosophila tissue culture cells unless substantial amounts of proteolysis inhibitors are included in the extraction buffer. This intrinsic proteolytic activity is substantially reduced during heat shock. An artifactual appearance that poly(A)-binding protein is specifically degraded by heat shock can result. Several contradictory descriptions of PABP may also be related to its proteolysis. Repression of proteolysis is likely to reflect a physiologically significant regulatory event, based on recent examinations of HSP70 stability during and after heat shock. PMID- 8202364 TI - Systematic sequencing of the Escherichia coli genome: analysis of the 2.4-4.1 min (110,917-193,643 bp) region. AB - The complete sequence analysis of the E. coli genome was initiated as a collaborative study in Japan. Following the initial analysis of the 0-2.4 min region (Yura, T. et al. (1992) Nucleic Acids Res. 20, 3305-3308), a contiguous sequence of 82,727 bp corresponding to the 2.4-4.1 min region (110,917-193,643 bp as counted from 0 min) was determined. The resulting sequence was found to contain at least 33 known genes and 24 putative genes predicted from protein sequence homology. PMID- 8202366 TI - Nonhomologous DNA end joining of synthetic hairpin substrates in Xenopus laevis egg extracts. AB - Processes of DNA end joining are assumed to play a major role in the elimination of DNA double-strand breaks (DSB) in higher eucaryotic cells. Linear plasmid molecules terminated by nonhomologous restriction ends are the typical substrates used in the analysis of joining mechanisms. However, due to their limited structural variability, DSB ends generated by restriction cleavage cover probably only part of the total spectrum of naturally occurring DSB termini. We therefore devised novel DNA substrates consisting of synthetic hairpin-shaped oligonucleotides which permit the construction of blunt ends and 5'- or 3' protruding single-strands (PSS) of arbitrary sequence and length. These substrates were tested in extracts of Xenopus laevis eggs known to efficiently join linear plasmids bearing nonhomologous restriction termini (Pfeiffer and Vielmetter, 1988). Sequences of hairpin junctions indicate that the short hairpins are joined by the same mechanisms as the plasmid substrates. However, the bimolecular DNA end joining reaction was only detectable when both hairpin partners had a minimal duplex stem length of 27bp and their PSS-tails did not exceed 10nt. PMID- 8202367 TI - Chimeric YACs were generated at unreduced rates in conditions that suppress coligation. AB - Chimerism is a major limitation of current YAC libraries. A method based on partially filled-in ends of restriction fragments was designed to avoid coligation as a possible source of chimeras. Model experiments using plasmid DNA as an insert showed that coligation was clearly avoided by this method. Pilot collections of YACs with an average insert size of 650kb were then constructed with and without the partial fill-in treatment. Starting from a mixture of a equal amounts of human and mouse DNA, none of 108 clones was positive by hybridization with both Alu and B2 probes, again suggesting that coligation was effectively blocked. However, 4 out of 10 clones still hybridized to 2 or more locations by FISH on chromosomes in human metaphase spreads, level similar to that in the clones made without the partial fill-in step. These results strongly suggest that chimeric clones generally arise by a mechanism independent of coligation, presumptively based on recombination. PMID- 8202369 TI - Interaction of small ribosomal and transfer RNAs with a protein from Leishmania donovani. AB - Using synthetic antisense RNA from the 5'-untranslated region of the beta-tubulin gene as probe in gel retardation assays, a heat stable RNA-binding factor was identified in promastigotes of the kinetoplastid protozoan Leishmania donovani. The same or similar factors interact with several small ribosomal RNA (srRNA) species and, more weakly, with tRNA, as shown by binding and competition experiments. Deletion analysis indicated involvement of repeated purine-rich motifs on the antisense RNA, in the reaction. Related, conserved motifs occur on at least two of the srRNAs. By a modified Western blot assay, the RNA-binding species was identified as a single, small polypeptide. The activity is apparently specific for the promastigote stage of the parasite, being undetectable in amastigotes. The properties of this RNA-binding factor suggest that it is a novel, previously uncharacterized protein. PMID- 8202368 TI - The POU domains of the Oct1 and Oct2 transcription factors mediate specific interaction with TBP. AB - We had previously shown that the ubiquitous Oct1 and the lymphoid-specific Oct2 transcription factors stimulate transcription at the level of stable preinitiation complex formation. We have therefore investigated whether the octamer binding proteins might physically interact with TBP, the TATA box binding protein component of the TFIID factor. By using several different experimental systems we show that TBP efficiently associates with Oct1 and Oct2. The interaction is direct and does not depend on the presence of DNA or additional proteins. N- and C-terminal deletions of the different proteins were used to localize the domains involved in the interaction. We show that the POU homeodomain of Oct2 and the evolutionarily conserved C-terminal core domain of TBP are both required and sufficient for the interaction. The Oct1 POU domain, which is highly homologous to the Oct2 POU domain, likewise mediates interaction with TBP. The interaction can also be observed in vivo, as TBP can be co precipitated with Oct2 from co-transfected Cos1 cells and TBP co immunoprecipitates with the endogenous Oct1 from HeLa cells. Co-transfection of human TBP and Oct2 expression vectors into B cells resulted in a synergistic activation of an octamer motif containing promoter. PMID- 8202370 TI - Increased removal of 3-alkyladenine reduces the frequencies of hprt mutations induced by methyl- and ethylmethanesulfonate in Chinese hamster fibroblast cells. AB - We have previously reported the isolation of mammalian cell lines expressing the 3-methyladenine DNA glycosylase I (tag) gene from E. coli. These cells are 2-5 fold more resistant to the toxic effects of methylating agents than normal cells (15). Kinetic measurements of 3-methyladenine removal from the genome in situ show a moderate (3-fold) increase in Tag expressing cells relative to normal as compared to a high (50-fold) increase in exogenous alkylated DNA in vitro by cell extracts. Excision of 7-methylguanine is as expected, unaffected by the tag+ gene expression. The frequency of mutations formed in the hypoxanthine phosphoribosyl transferase (hprt) locus was investigated after methylmethanesulfonate (MMS), ethylmethanesulfonate (EMS), N-nitroso-N-methylurea (NMU) and N-nitroso-N ethylurea (NEU) exposure. Tag expression reduced the frequency of MMS and EMS induced mutations to about half the normal rate, whereas the mutation frequency in cells exposed to NMU or NEU is not affected by the tag+ gene expression. These results indicate that after exposure to compounds which produce predominantly N alkylations in DNA, a substantial proportion of the mutations induced is formed at 3-alkyladenine residues in DNA. PMID- 8202371 TI - The promoter of the Xwnt-5C gene contains octamer and AP-2 motifs functional in Xenopus embryos. AB - The Xwnt-5C gene is expressed in Xenopus embryos from the early gastrula stage onwards. The transcription of Xwnt-5C is regulated differentially with respect to transcript size, timing and localization. To gain insight into the generation of the Xwnt-5C expression pattern, we started to analyze the transcriptional regulation of this gene. We isolated Xwnt-5C genomic DNA sequences. By microinjection of chimaeric reporter constructs into Xenopus embryos we demonstrate that the upstream region contains a promoter functional in vivo. Of the several putative binding sites for trans-acting factors, present in a minimal promoter fragment, some have been studied in more detail. Mutations in an octamer motif and in an AP-2 consensus sequence interfere with the activity of the Xwnt 5C minimal promoter. In vitro binding assays with extracts from gastrula stage Xenopus embryos show that the octamer motif of the Xwnt-5C promoter can bind several Octamer binding factors, one of which is Oct1. PMID- 8202372 TI - DNA stability at temperatures typical for hyperthermophiles. AB - We have studied the fate of covalently-closed circular DNA in the temperature range from 95 to 107 degrees C. Supercoiled plasmid was not denatured up to the highest temperature tested. However, it was progressively transformed into open DNA by cleavage and then denatured. Thermodegradation was not dependent on the DNA supercoiling density. In particular, DNA made positively supercoiled by an archaeal reverse gyrase was not more resistant to depurination and thermodegradation than negatively supercoiled DNA. Thermodegradation was similar in aerobic or anaerobic conditions but strongly reduced in the presence of physiological concentrations of K+ or Mg2+. These results indicate that the major problem faced by covalently closed DNA in hyperthermophilic conditions is not thermodenaturation, but thermodegradation, and that intracellular salt concentration is important for stability of DNA primary structure. Our data suggest that reverse gyrase is not directly required to protect DNA against thermodegradation or thermodenaturation. PMID- 8202373 TI - Mitochondrial transcripts are processed but are not edited normally in Trypanosoma equiperdum (ATCC 30019) which has kDNA sequence deletion and duplication. AB - Analyses of the Trypanosoma equiperdum (ATCC 30019) maxicircle reveals deletions, duplications and rearrangement compared to T. brucei. The genes for 9S rRNA and 12 proteins are absent. The 12S rRNA and cytochrome oxidase subunit I (COI) genes lack their 3' ends and are adjacent indicating deletion of intervening genes. The remaining two NADH dehydrogenase subunit genes (ND4 and ND5), the ribosomal protein RPS12 gene and the CR5 gene are duplicated and rearranged. ND4, RPS12 and the CR4 transcripts are abundant in steady state RNA while 12S rRNA and COI transcripts are not detected. Full length ND5 transcripts are rare, if present, but chimeric ND5/ND4 transcripts are abundant. The CR4 and RPS12 transcripts are the size of unedited RNAs suggesting that they are processed. However, they are not edited normally, presumably due to the absence of minicircle gRNA genes. PMID- 8202374 TI - A rapid scanning strip for tri- and dinucleotide short tandem repeats. AB - Oligonucleotides representing 60 trinucleotide (21mers) and four dinucleotide (20mers) tandem repeats were directly synthesized and arrayed onto an aminated polypropylene substrate. DNA samples of different complexities (a CAG-containing 21mer oligonucleotide, PCR fragments of 200 to 3,000 bp, and cosmids with 31 to 35 kb inserts) were radiolabelled and hybridized to the oligonucleotide array at various temperatures. When compared to sequence data available from the test DNAs, the reverse blot system specifically identified various tri- and dinucleotide short tandem repeats (STRs) in every case. Moreover, there was no random or cross hybridization to nonspecific sequences. It was possible to detect as few as three repeated units in a particular location, as shown for (CCT)n, (GCC)n and (CAC)n triplets in cosmid DNA. Varying the hybridization stringency can enhance the detection of STRs. This single-step reverse blot system therefore allows the rapid, specific and sensitive identification of various STRs in DNA sources of different complexity. PMID- 8202375 TI - The unusual nucleotide content of the HIV RNA genome results in a biased amino acid composition of HIV proteins. AB - Extremely high frequencies of the A nucleotide are found in the RNA genomes of the lentivirus group of retroviruses. It is presently unknown what molecular force is responsible for this A-pressure. In this manuscript, we demonstrate a correlation between this 'A-pressure' and the amino acid-usage of the lentivirus family. We compared the amino acid composition of the Gag and Pol proteins of the human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) with that of the second group of human retroviruses; the human T-cell leukemia viruses type I and II (HTLV-I and HTLV-II). Differences in total amino acid content correlate with the preference for A-rich codons in the HIV genome. A pair-wise comparison of homologous amino acid positions in the Pol proteins indicates that both conservative and non-conservative changes can be accounted for by this A-bias. The putative molecular mechanism underlying this A-pressure and the evolutionary consequences are discussed. PMID- 8202376 TI - A tRNA gene mapping within the chloroplast rDNA cluster is differentially expressed during the development of Daucus carota. AB - In vivo analysis of expression of the chloroplast rDNA cluster during somatic embryogenesis of Daucus carota (D.carota) was performed by Northern-blot analysis with different DNA probes, spanning both the 16S rRNA gene, the 16S-23S rRNA spacer, which contains the two mosaic tRNA genes tRNA(Ile) and tRNA(Ala), and the region upstream of the 16S rRNA gene, where a tRNA(Val) maps. We show that expression both of the spacer tRNAs tRNA(Ile) and tRNA(Ala) is not significantly regulated during development whereas the amount of the transcript corresponding to tRNA(Val) is not detectable during early embryonic stages and progressively accumulates during late phases. Multiple transcription start sites have been identified upstream of the tRNA(Val) gene by S1 mapping analysis, which are activated late during the embryogenesis. These data indicate that developmental control mechanisms act on plastid gene expression during embryogenesis in carrot. PMID- 8202377 TI - Identification of a mariner-like repetitive sequence in C. elegans. AB - A repetitive element in C.elegans has been found that bears high homology to the element mariner of Drosophila mauritiana (EMBL accession number X77804). This element is present in about 20 copies in the N2 strain of C.elegans, and appears in roughly equal copy numbers in the related strain BO and in the hybrid strains RW7097 and TR679. There is only one copy of this MLE in three related species of Caenorhabditis. A cDNA of this mariner-like element (MLE) codes for a protein with 58% homology to the Drosophila transposase. The mariner-like element is not mobile in N2. This class of elements has now been described in insects, planaria and nematodes (GenBank accession number M98552 and this report). PMID- 8202378 TI - Mutational analysis of the PRP4 protein of Saccharomyces cerevisiae suggests domain structure and snRNP interactions. AB - The PRP4 protein of Saccharomyces cerevisiae is an essential part of the U4/U6 snRNP, a component of the mRNA splicing apparatus. As an approach to the determination of structure-function relationships in the PRP4 protein, we have isolated more than fifty new alleles of the PRP4 gene through random and site directed mutagenesis, and have analyzed the phenotypes of many of them. Twelve of the fourteen single-point mutations that give rise to temperature-sensitive (ts) or null phenotypes are located in the portion of the PRP4 gene that corresponds to the beta-transducin-like region of the protein; the remaining two are located in the central portion of the gene, one of them in an arginine-lysine-rich region. Nine additional deletion or deletion/insertion mutations were isolated at both the amino- and carboxy-termini. These data show that the amino-terminal region (108 amino acids) of PRP4 is non-essential, while the carboxy-terminal region is essential up to the penultimate amino acid. A deletion of one entire beta-transducin-like repeat (the third of five) resulted in a null phenotype. All ts mutants show a first-step defect in the splicing of U3 snRNA primary transcript in vivo at the non-permissive temperature. The effects on prp4 mutant growth of increased copy-number of mutant prp4 genes themselves, and of genes for other components of the U4/U6 snRNP (PRP3 and U6 snRNA) have also been studied. We suggest that the PRP4 protein has at least three domains: a non-essential amino-terminal segment of at least 108 amino acids, a central basic region of about 140 residues that is relatively refractile to mutation and might be involved in RNA interaction, and an essential carboxy-terminal region of about 210 residues with the five repeat-regions that are similar to beta-transducins, which might be involved in protein-protein interaction. A model of interactions of snRNP components suggested by these results is presented. PMID- 8202379 TI - Over-representation of the disease associated (CAG) and (CGG) repeats in the human genome. AB - Expansion of trimer repeats has recently been described as a new type of human mutation. Of the 64 possible trimer compositions, only the CGG and CAG repeats have been implicated in genetic diseases. This study intends to address two questions: (1) What makes the CGG and CAG repeats unique? (2) Could other trimer repeats be involved in this type of mutation? By computer analysis of trimer and hexamer frequency distributions in approximately 10 Mb of human DNA, twenty trimer motifs (ten complementary pairs) have been identified that are the most likely to be expanded. The frequency distribution study also indicated that the expanded trimer motif in Fragile-X syndrome is GGC instead of CGG. DNA linguistics studies revealed that the GGC/GCC and CAG/CTG repeats were over represented in the human genome. Further analysis of base composition suggested that the CCA/TGG repeats may be involved in the trimer expansion mutation since they possessed many similar characteristics to GGC/GCC and CAG/CTG. The computer aided sequence analysis studies reported here may help to understand the molecular mechanisms of trimer repeat expansion. PMID- 8202380 TI - Aryl hydrocarbon-induced interactions at multiple DNA elements of diverse sequence--a multicomponent mechanism for activation of cytochrome P4501A1 (CYP1A1) gene transcription. AB - In vivo footprinting experiments, augmented with gel shift and transfection analyses suggest that activation of the CYP1A1 gene by aryl hydrocarbons may be a multicomponent process. During the first 30 minutes of exposure to aryl hydrocarbon carcinogens and environmental contaminants, in vivo footprints appear at nine distinct sites within a 281 bp region centered 950 bp upstream of the CYP1A1 transcription start site. Six of these sites are unrelated in sequence to the three xenobiotic response elements (XREs) within this region, at which the aryl hydrocarbon (AH) receptor is known to bind. These six display a variety of footprint patterns, are diverse in sequence and range in G-C content from 60 to 75%. This diversity suggests that multiple nuclear factors may be responsible for these six in vivo footprints. These observations are consistent with competition gel shift experiments showing that the nuclear factors binding at two of these sites are different from each other, as well as from the AH receptor. Gel shifts also indicate that the sequence-specific factors binding at these sites are expressed constitutively. This is consistent with a model in which in vivo footprints are induced at these six sites, not through direct activation or de novo synthesis of DNA-binding factors, but through a two phase mechanism in which binding of the nuclear AH receptor complex to XREs facilitates the binding of constitutive factors at these sites. This facilitation could be mediated either through specific protein-protein interactions or through alterations in chromatin structure that make these sites accessible to constitutive nuclear factors. A function for the sequences at which aryl hydrocarbons induce in vivo footprints is suggested by transfection experiments showing that one of these sequences cooperates with a weak XRE to confer on a reporter gene responsiveness to aryl hydrocarbons. PMID- 8202381 TI - Fission yeast gene structure and recognition. AB - A database of 210 Schizosaccharomyces pombe DNA sequences (524,794 bp) was extracted from GenBank (release number 81.0) and examined by a number of methods in order to characterize statistical features of these sequences that might serve as signals or constraints for messenger RNA splicing. The statistical information compiled includes splicing signal (donor, acceptor and branch site) profiles, translational initiation start profile, exon/intron length distributions, ORF distribution, CDS size distribution, codon usage table, and 6-tuple distribution. The information content of the various signals are also presented. A rule-based interactive computer program for finding introns called INTRON.PLOT has been developed and was used to successfully analyze 7 newly sequenced genes. PMID- 8202382 TI - A versatile support for the synthesis of oligonucleotides of extended length and scale. PMID- 8202383 TI - pha-1, a selectable marker for gene transfer in C. elegans. PMID- 8202385 TI - Application of inverse PCR to isolation of end probes from cosmids. PMID- 8202384 TI - Rapid method for screening and cloning cDNAs generated in differential mRNA display: application of northern blot for affinity capturing of cDNAs. PMID- 8202386 TI - PCR amplification of antibody variable regions using primers that anneal to constant regions. PMID- 8202387 TI - Arbitrarily primed PCR fingerprints resolved on SSCP gels. PMID- 8202388 TI - A powerful new technique to quickly prepare hundreds of plant extracts for PCR and RAPD analyses. PMID- 8202389 TI - Purification of genomic DNA from human whole blood by isopropanol-fractionation with concentrated Nal and SDS. PMID- 8202390 TI - Partitioned pulsed-field gel electrophoresis-PCR (PPF-PCR): a new method for pulsed-field mapping for STS and microsatellites. PMID- 8202391 TI - A yeast mating-selection scheme for detection of protein-protein interactions. PMID- 8202392 TI - Increased detection of polymorphism among randomly amplified wheat DNA fragments using a modified temperature sweep gel electrophoresis (TSGE) technique. PMID- 8202393 TI - Refinement of the Stetler/Marram model for application of research findings to practice. PMID- 8202394 TI - Nurses' attitudes toward homeless women: a barrier to change. AB - Close to a third of the almost 4 million homeless persons in the United States are women. They have multiple physical and mental health problems directly attributable to their homelessness. Studies have indicated that their failure to seek health care is partially a function of the barrier created by negative attitudes of nurses toward homeless women. Strategies for changing nurses' attitudes, built on attitude change theory, include methods for increasing knowledge and experience in the treatment of homeless women. PMID- 8202395 TI - The Patient Self-Determination Act: sources of concern for nurses. PMID- 8202397 TI - Exciting times. PMID- 8202396 TI - Violence as a nursing priority: policy implications. PMID- 8202398 TI - Nurse case management from the client's view: growing as insider-expert. PMID- 8202399 TI - Adult congenital heart disease. An emerging population. AB - Although there are few cures for congenital heart disease (CHD), more patients are now surviving to adulthood. Possible causes of CHD include teratogenic, genetic, and random factors, or an interaction of various factors. The risk of CHD recurrence is dependent on its presumed mode of inheritance. Because there may be a greater risk of transmission as survival rates increase, at-risk parents and families need to recognize the potential benefits of prevention. For the adult survivors, life remains a constant challenge of coping with persistent health problems, uncertain long-term functional status, and the influence of societal values. PMID- 8202400 TI - Common congenital heart defects. Long-term follow-up. AB - Dramatic advances in the diagnosis and treatment of patients with congenital heart disease (CHD) have profoundly increased their survival rate. More than 500,000 patients in the United States with functionally significant congenital cardiac defects have reached adulthood. The focus of this article is to present an overview of the long-term surgical outcomes of the following common congenital heart defects: atrial septal defect, pulmonary stenosis, ventricular septal defect, coarctation of the aorta, aortic stenosis, tetralogy of Fallot, and transposition of the great arteries. PMID- 8202401 TI - Infective endocarditis. Implications for care of the adult with congenital heart disease. AB - Infective endocarditis (IE) remains a severe complication for the adult with congenital heart disease (CHD). The last four decades have witnessed a radical transformation in the spectrum of IE, including the advent of cardiac surgery and the postantibiotic era. Because of the devastation caused by this disease, prevention is the hallmark. A clear understanding of the pathogenesis, clinical features, and management of IE is essential for any practitioner caring for adults with CHD. PMID- 8202402 TI - Reproductive issues for the woman with congenital heart disease. AB - As the number of women with congenital heart disease continues to rise, information regarding reproduction is and will become an important part of their follow-up care. Until now the focus of reproduction has been on pregnancy outcomes. Practitioners must become better informed about issues of fertility, contraception, and childbearing to better advise their patients. PMID- 8202403 TI - Educational assessment of the adult with congenital heart disease. AB - Adults with congenital heart disease (CHD) have specific educational needs that are influenced by a variety of factors. This article identifies and discusses learning needs and factors that impact educational outcomes for the adult CHD patient population. Assessment techniques and an assessment tool are presented to guide the nurse through the process of assessing an adult patient seeking health care for this disease. PMID- 8202404 TI - Employability and career counseling for adolescents and adults with congenital heart disease. AB - Employability is an important issue for adolescents and young adults with congenital heart disease. This article provides an overview of specific federal laws that protect these individuals and information about state vocational rehabilitation programs. Guidelines are provided to help health care providers counsel their patients more effectively. PMID- 8202405 TI - Insurability issues facing the adolescent and adult with congenital heart disease. AB - Access to comprehensive health care coverage for congenital heart disease patients is often limited because of their "preexisting condition." Life insurance may be difficult to obtain if the congenital lesion carries a higher than standard mortality rating. Various insurance program options are available to many of these patients. Knowledgeable health care professionals can assist these individuals to obtain the needed coverage, enabling better medical and financial security for this growing patient population. PMID- 8202406 TI - Physical activity and congenital heart disease. AB - With advances in the diagnosis and management of congenital heart disease (CHD), the need has arisen for the assessment and counseling of patients as to appropriate physical activity levels through adulthood. Considerations to be evaluated before making exercise and athletic activity recommendations to the patient with CHD are outlined. Recommended guidelines of the American Heart Association are presented for recreational and occupational activities. Selected congenital heart defects are reviewed to address potential negative effects of incorrect recommendations. PMID- 8202407 TI - The role of the clinical specialist in an adult congenital heart disease program. AB - As the specialty of adult congenital heart disease (CHD) develops, there is concern regarding the training of the health professional who will be responsible for patient management. Integral to the program is the role of the clinical nurse specialist. An advanced practice role, the clinical nurse specialist provides her or his expertise to both the daily operation of the program and to the clinical management and education of patients and their families. The educational preparation and roles of a clinical specialist in adult CHD are described. PMID- 8202408 TI - Health care reform: meeting the challenges. PMID- 8202409 TI - The diabetic neuropathic foot: a triple crush syndrome--measurement of compartmental pressures of normal and diabetic feet. AB - The role of chronic swelling in the feet of diabetic patients with severe neuropathy is unclear. It was hypothesized that swelling might raise the compartment pressures of the foot high enough above normal to produce nerve and soft tissue injury, ie, the triple crush syndrome. Four compartment measurements were recorded in 30 feet of 15 normal patients and in 34 feet of 20 patients with severe diabetic neuropathy and normal large vessel arterial blood flow. The lateral compartments produced unreliable results and were discarded from statistical evaluation. The mean medial compartment pressure was 7.8 mm Hg (SD 2.55) in the normal feet and 9.4 mm Hg (SD 4.08) in the diabetic feet. This was not a statistically significant difference. Highly significant differences were recorded in the interosseous and central compartments where the mean pressures were 6.4 mm Hg (SD 2.72) and 5.7 mm Hg (SD 2.89), respectively, in the normal feet and 9.3 mm Hg (SD 4.75) and 8.9 mm Hg (SD 5.0) in the diabetic feet (P < .05 for each group). Furthermore, within the diabetic group, 9 of 9 patients (100%) with clinically swollen feet had at least one compartment pressure measure two standard deviations (12 mm Hg) or greater compared with 5 of 11 (45%) in those without clinical swelling. This difference is significant (P < .01). We could not correlate elevated compartment pressures directly with soft tissue pathology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202410 TI - A new neck preserving total hip arthroplasty for the young patient. AB - A retrospective review of a femoral neck preserving custom total hip replacement was performed on seven young patients with disabling hip arthrosis. This design was created to provide greater rotational control to off-axis load and to provide greater proximal medial support to counteract varus bending forces. Eight hip arthroplasties, with a minimum follow up of 24 months, were reviewed and all had good and excellent clinical Harris scores. Presented is a treatment alternative to the standard total hip replacement. PMID- 8202411 TI - Hydroxyapatite coatings. AB - A series of investigations over the past several years has evaluated a number of implant materials with and without plasma-sprayed hydroxyapatite (HA) coatings for use in load-bearing implant applications. HA-coated implants have exhibited greater interface shear attachment characteristics when compared to uncoated implants; these results have been demonstrated with dense (flat), porous-coated, and macrotextured implant surfaces. Maximum attachment strength also was found to occur within a shorter period of time postoperatively with the HA-coated samples, indicating a more rapid tissue adaptation to the implant surfaces. Plasma-sprayed HA coatings provide an osteophilic and osteoconductive surface that increases both the bone-implant attachment strength, as well as the rate of bone adaptation to the HA-coated implant surface. PMID- 8202412 TI - Atraumatic posterior pelvic ring fractures simulating metastatic disease in patients with metabolic bone disease. PMID- 8202414 TI - Spontaneous rupture of digital flexor tendons. PMID- 8202413 TI - Osteoid osteoma of the proximal femur: CT-guided preoperative localization. PMID- 8202415 TI - Antibiotic-induced diarrhea and pseudomembranous colitis. AB - Pseudomembranous colitis is commonly associated with the use of antibiotics but may follow administration of other drugs and has occurred in patients who have not received any medication. Cases related to antibiotic administration are thought to be due to changes in normal intestinal flora that allow overgrowth of Clostridium difficile and elaboration of toxin. Clusters of cases in hospitals suggest nosocomial transmission of the bacteria. The stool cytotoxin assay is the most specific test for pseudomembranous colitis. Oral vancomycin (Vancocin) is preferred for the treatment of severe cases. It is recommended that hospital personnel caring for patients infected with C difficile wear gloves and wash their hands carefully after contact. PMID- 8202416 TI - Lumbar puncture and CSF examination. Answers to three commonly asked questions. AB - The incidence of post-lumbar puncture headache has been shown to be reduced by using a higher-gauge (smaller-bore) needle and orienting the needle bevel parallel to the dural fibers. Incidence of headache is the same in patients given bed rest as in patients who are mobilized immediately. Cerebrospinal fluid (CSF) examination of patients with seizures of unclear cause is indicated. However, pleocytosis can be a result of the seizure alone. Other causes of pleocytosis must be ruled out by clinical evaluation and CSF studies. Although lumbar puncture is often advocated for patients presenting with dementia, it usually is not helpful in finding a specific cause if the dementia is long-standing. PMID- 8202417 TI - Points to fight for ... and points to fight against! PMID- 8202418 TI - Wilson's disease. Psychiatric manifestations may be the clinical presentation. AB - It is important to consider Wilson's disease in patients with psychiatric signs and symptoms who also have abnormal liver function test results or neurologic findings, or both. Thorough evaluation of emotionally disturbed persons, including complete history taking, careful physical examination, and appropriate laboratory profile, generally rules out or arouses suspicion of Wilson's disease during routine screening. Laboratory abnormalities necessitate repeated studies and additional family and personal history taking with emphasis on possible Wilson's disease. Further workup may then be indicated. Prompt recognition and vigorous, consistent treatment can minimize symptoms and tissue damage. Identifying a case of Wilson's disease and seeing clinical aspects improve with appropriate therapy is gratifying. PMID- 8202419 TI - Renal adaptation to the failing heart. Understanding the cascade of responses. AB - Progressive systolic dysfunction of the heart results in a broad array of physiologic compensatory mechanisms within the kidney. These mechanisms are primarily stimulated by diminution of the effective arterial blood volume and resultant activation of a biochemical cascade of neurohormonal responses, including activation of the renin-angiotensin-aldosterone system and enhanced release of norepinephrine, arginine vasopressin, prostaglandins, endothelin, and atrial natriuretic peptide. The interaction of these neurohormonal systems within the kidney is complex. Vasoconstriction induced by angiotensin II, arginine vasopressin, and catecholamines may decrease renal perfusion by both endocrine and neural actions. In contrast, systemic pressures may rise, which may facilitate perfusion. PMID- 8202420 TI - Renal adaptation to the failing heart. Avoiding a 'therapeutic misadventure'. AB - Systolic dysfunction of the heart represents a state of "prerenal" azotemia, in which the excess of total body salt and water is redistributed to venous and interstitial fluid compartments. This results in a diminished effective circulating blood volume and thereby decreases tissue perfusion. The kidneys perceive the ineffective circulating volume and employ a complex series of interconnected hemodynamic and neurohumoral effector mechanisms to restore "adequate" perfusion. This is done by reclaiming a greater fraction of filtered sodium and water and elevating systemic vascular resistance to keep perfusion pressure to vital organs constant despite diminished cardiac output. Knowledge of the physiologic compensatory responses that occur in the kidneys of heart failure patients allows clinicians to develop a logical treatment plan. This knowledge should also help avoid a therapeutic misadventure by making it possible to exclude drugs known to adversely affect renal function in patients with a failing heart and poorly compensating kidneys. PMID- 8202421 TI - Acute polyarthritis. Fifth disease passed from child to adult. AB - Physicians are familiar with the "slapped cheek" rash seen in childhood cases of erythema infectiosum. Less well known is that infection with its pathogen, parvovirus B19, often becomes manifest in adults as acute viral arthropathy. In evaluation of suspected cases, a complete blood cell count and blood chemistry profile are useful additions to thorough history taking and physical examination. Differential diagnosis includes Lyme disease, other viral infections, acute rheumatoid arthritis, systemic lupus erythematosus, and psoriatic arthritis. Treatment is symptomatic with nonsteroidal anti-inflammatory drugs. PMID- 8202422 TI - AAFP's president on support of Clinton plan. PMID- 8202423 TI - Effective use of insulin. A balancing act. AB - The effective use of insulin requires familiarity with how the hormone acts as well as appreciation of such modifying factors as insulin antibodies, exercise, and smoking. Optimal insulin use is facilitated by knowledge of the dawn phenomenon, which causes insulin resistance in early morning hours. Rebound hyperglycemia should be treated much more conservatively than comparable hyperglycemia due to other causes because of the greater likelihood of recurrent hypoglycemia. Diet, exercise, and insulin dosage must be balanced in order to attain good diabetes control, and this balance is possible only when it is guided by regular self blood glucose monitoring. PMID- 8202424 TI - Diagnosing obstructive lung disease. Why is differentiating COPD from asthma important? AB - Chronic obstructive pulmonary disease (COPD) and asthma are the main causes of obstructive lung disease, and mortality rates of both diseases are on the increase. Smoking is the major risk factor for COPD. Airway hyperreactivity and reversibility of airflow obstruction, once considered hallmarks of asthma, may also be seen in COPD. Asthma is increasingly being recognized as a chronic inflammatory airway disease. COPD and asthma can be diagnosed through careful history taking, physical examination, spirometry, and other ancillary tests. More widespread use of peak expiratory flow rates should aid in diagnosis and monitoring. PMID- 8202425 TI - Maintenance therapy for obstructive lung disease. How to achieve the best response with the fewest agents. AB - Asthma is now thought to be primarily an inflammatory condition with secondary bronchospasm; hence, the mainstay of maintenance therapy is an inhaled anti inflammatory drug, either a corticosteroid (especially in adults) or a mast-cell stabilizer (especially in children). Inhaled beta agonists are reserved for acute exacerbations and systemic corticosteroids for severe refractory disease. Oral theophylline is sometimes helpful, especially for nocturnal exacerbations. Chronic bronchitis and emphysema almost always stem from cigarette smoking. Bronchospasm is the predominant cause of symptoms, and maintenance therapy with an inhaled anticholinergic (eg, ipratropium bromide [Atrovent]) is the best approach. If symptoms are not controlled, an inhaled bronchodilator should be added. An oral or inhaled corticosteroid benefits a minority of patients. Theophylline is especially helpful for chronic bronchitis and nocturnal exacerbations. PMID- 8202426 TI - B haplotype influence on the relative efficacy of Marek's disease vaccines in commercial chickens. AB - The objectives were to investigate whether or not B haplotypes influence vaccinal immunity against Marek's disease (MD) in commercial chickens and to evaluate whether retrospective analysis would detect the influence. This method involved evaluating the B haplotypes of turkey herpesvirus (HVT)-vaccinated sick vs normal chickens from a flock afflicted with MD symptoms. An analysis of the retrospective data disclosed that MD symptoms were present in a higher proportion of B2B19 than B2B21 chickens. A prospective study was then conducted with blood typed chickens of the strain vaccinated with HVT or HVT + 301B bivalent MD vaccines prior to inoculation of the very virulent Md5 virus. The bivalent vaccine provided better protection than HVT alone, but with either vaccine fewer B2B21 chickens developed MD lesions. We conclude that the B haplotype influence on vaccinal immunity against MD previously demonstrated in B-congenic strains of chickens is also significant in commercial chickens and that the influence can be detected through analysis of B haplotypes in sick vs normal chickens of an affected flock. PMID- 8202427 TI - Male-mediated venereal transmission of endogenous avian leukosis virus. AB - Congenital transmission of avian leukosis viruses (ALV) occurs readily through the egg, but transmission of ALV through male seminal fluid is considered to be nonexistent or rare. Progeny from mating endogenous late-feathering (LF), K/k+ males carrying an endogenous virus gene (ev21) with virgin early-feathering (EF) k+/w females were examined for the presence of infectious endogenous virus EV21 using an enzyme-labeled immunoassay for viral capsid antigen p27. All 177 LF chicks expressed EV21, p27, and 171 of 175 EF chicks did not express p27. Blood from the four p27-positive EF chicks revealed only infectious Subgroup E ALV as determined by subgroup-specific virus assays. Southern blot DNA hybridizations, however, ruled out germline integration of EV21 among the four infected EF progeny. Virus EV21 was not shed in albumens of the dams. Moreover, antibodies against ALV Subgroups A and E were not detected in dams 17 wk after the first insemination. Chicks infected with EV21 were found only in the first two of six hatches. Data suggested direct infection of the embryos from viremic semen rather than congenital infection through infected hens. Direct male transmission of EV21 to progeny may be the basis for persistence of refractory lines noted in some ALV eradication programs. Based on the absence of recombinants among 352 progeny, ev21 and K appear to be less than .3 cM apart. PMID- 8202428 TI - Laying hen performance as influenced by protein intake to sixteen weeks of age and body weight at point of lay. AB - White Leghorn chicks were fed corn-soybean meal diets containing 20, 17, 14, and 11% protein, with similar levels of energy, from hatch to 16 wk of age. Body weights at 16 wk were similar for pullets fed the 20 and 17% protein diets, but were reduced by 11 and 27% for birds fed the 14 and 11% protein diets, respectively, as compared with the 20% protein diet. At 16 wk of age, all birds were placed on a common 17% protein laying diet. Pullets fed the 14 and 11% protein laying diets were slightly slower coming into production, however, by 28 wk of age egg production was similar for all four growing treatment groups and remained so until the end of the experiment. Average egg weight was similar for pullets fed the two higher levels of protein during the growing period and significantly lower for those pullets fed the 11% grower diet for all except the 28- and 32-wk periods. Pullets fed the 14% grower diet produced eggs with average weights significantly lower than those for the higher protein diets from 40 to 58 wk of age. Although the results might be interpreted as indicating that higher protein growing diets result in body protein reserves that subsequently enhance egg size, it is more likely that the pullets consuming lower protein diets produce smaller eggs because they have smaller body weights. PMID- 8202429 TI - Resistance to Marek's disease in chickens with recombinant haplotypes to the major histocompatibility (B) complex. AB - Genetic resistance to Marek's disease (MD) is associated with the B-F region of the MHC. The resistance of chickens possessing either of two MHC haplotypes to challenge with different strains of MDV was examined. Chickens with serologically similar MHC recombinants BR2 and BR4 (both BF2-G23) were backcrossed for four generations to the highly inbred UCD-003 line (B17B17). Heterozygotes (B17BF2 G23) were mated to produce BR2BR2 and BR4BR4 homozygotes with 93% background gene uniformity. Both genotypes were highly resistant to GA-5 MDV, having an incidence of 0 and 8% MD for BR2BR2 and BR4BR4, respectively, whereas the incidence of MD in the UCD-003 birds was above 80%. Challenge with the very virulent RB-1B strain caused 10% and 31% MD in the BR2BR2 and BR4BR4 chickens, respectively, compared with 100% and 52% in the B17B17 (UCD-003) and B23B23 (New Hampshire 105) lines, respectively. Viremia levels at 5 and 6 d postinfection were significantly lower in BR2BR2 and B23B23 than in B17B17 genotypes. PMID- 8202430 TI - Effect of genetic strain, calcium, and feed withdrawal on growth, tibial dyschondroplasia, plasma 1,25-dihydroxycholecalciferol, and plasma 25 hydroxycholecalciferol in sixteen-day-old chickens. AB - Four experiments were conducted to study the effects of genetic strain, dietary Ca level, and feed withdrawal on growth, feed efficiency, tibia bone ash, tibial dyschondroplasia (TD), and plasma 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and 25-hydroxycholecalciferol [25(OH)D3]. Experiment 1 used five strains and Experiments 2 to 4 used three broiler strains. A TD-inducing basal diet was used in each experiment. In Experiment 3, the birds were fed .60 or .95% dietary Ca, and in Experiment 4 the birds were fed the basal diet and were fed or deprived of feed for 8 h daily. In Experiment 1, Athens-Canadian Randombred and Single Comb White Leghorn chicks did not develop TD. In birds fed the basal diet alone, Peterson x Hubbard chicks had a significantly higher incidence of the most severe TD lesion than two other broiler strains in each experiment and were significantly lighter in BW in two of the four experiments. Of the three broiler strains, the incidence and average lesion score of TD was significantly higher in Peterson x Hubbard birds in Experiment 2 and was numerically highest in the other three experiments. In birds fed the basal diet, Peterson x Hubbard birds had significantly higher plasma 1,25(OH)2D3 in two of the four experiments. Both feed deprivation and .95% Ca increased bone ash and decreased the incidence and severity of TD. There were no significant differences in plasma 1,25(OH)2D3 among strains of birds deprived of feed or fed .95% Ca. In three of the four experiments, high plasma 1,25(OH)2D3 in Peterson x Hubbard birds was associated with an increase in the incidence and severity of TD. PMID- 8202431 TI - Levels of various elements of concern in feed phosphates of domestic and foreign origin. AB - Thirty-six feed phosphates, including nine mono-dicalcium phosphates (M-DCP, 21% P), 13 di-monocalcium phosphates (D-MCP, 18.5% P), and 14 thermochemically produced defluorinated phosphates (DFP, 18.0% P), were analyzed for moisture, Ca, P, and 9 essential minerals (K, Mg, Na, Cl, Fe, Cu, Mn, Se, and Zn). Also, nine potentially toxic elements (Al, F, As, Cd, Cr, Hg, Pb, Ni, and V) were determined. All of the M-DCP were of domestic origin; 5 of the 13 D-MCP samples were obtained in Algeria, Peru, Holland, and South Africa. The DFP samples included 10 domestic products, 2 samples from Russia, 1 from Poland, and 1 from Japan. Levels of Na were high in the DFP samples (3.96 to 5.78%), except for the two Russian samples, which contained only .16 and .19%. Magnesium levels varied from .09 to .76%, .02 to 1.21%, and .01 to 1.54% in the M-DCP, D-MCP, and DFP samples, respectively. Two Russian DFP samples contained 1.51 and 1.54% Mg. Chlorine levels were generally quite low (.002 to .020%); however, two precipitated D-MCP samples contained .12 and 1.47% Cl. Iron levels were high (.24 to 1.41%) in all samples except the bone-precipitated D-MCP (.039%), and the reference standard, calcium phosphate, dibasic dihydrate, USP (.029%). Levels of Cu, Mn, and Zn were quite variable. Cadmium varied from < 1 ppm in the DFP samples to 67 ppm in one experimental M-DCP. Vanadium levels varied from 20 to 796 ppm in one experimental M-DCP sample. Fluorine levels were in the acceptable range, .05 to .21%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202432 TI - Effect of early feed restriction and realimentation on heat production and changes in sizes of digestive organs of male broilers. AB - Two experiments were conducted with broilers to determine the effect of early feed restriction and realimentation on metabolic heat production and changes in sizes of digestive organs. An indirect open circuit calorimeter was used. Treatments were a full-fed control (FF) and a feed-restricted group (FR). Feed during the restriction period (6 to 12 d) for the FR birds was limited to 50% of voluntary feed intake of the FF birds. This was followed by realimentation period when all birds were provided feed for ad libitum consumption. The purpose of Experiment 1 was to measure basal metabolic rate (BMR), and Experiment 2 was designed to measure 36-h fasting metabolic rate (FMR), in both cases during time of restriction and realimentation. At the end of the 36-h unfed period, birds were killed and their digestive organs excised, blotted, and weighed. The FR birds showed significantly (P < .01) lower BMR compared with the FF birds during the restriction period. This lower BMR did not carry over into the refeeding period, when there was no difference between the two treatments. Thirty-six-hour FMR, like the BMR was also lower for FR compared with FF birds, but only during the period of restriction. Weights of digestive organs (expressed as a percentage of BW) during restriction were generally heavier for FR compared with FF birds. Measurements of organ weights taken during realimentation show significantly (P < .05) heavier liver and pancreas for FR compared with FF birds. Results of these experiments suggest that lower MR of "restricted-refed" birds does not play a role in the ability of the birds to show improved feed efficiency and growth compensation. Greater feed intake relative to BW and its associated digestive adaptations seem to be contributing factors to any growth compensation. PMID- 8202433 TI - Microsatellite markers for genetic mapping in the chicken. AB - Microsatellite markers have been found to be abundant, evenly distributed, and highly polymorphic in a number of eukaryotic genomes. The objective of this study was to determine the utility of (TG)n microsatellites in the chicken. A chicken library enriched for (TG)n repeats was generated and 42 unique clones containing (TG)n microsatellites were identified and sequenced. The number of uninterrupted TG repeats ranged from 4 to 14 with an average of 7.8, which was considerably less than the number of repeats found in mammalian species. When primers designed to amplify across the (TG)n microsatellites were used in polymerase chain reactions (PCR) containing genomic chicken DNA, 19 of the 33 primer sets examined yielded polymorphisms in at least one of the three sets of chicken families: 15, 11, and 11 primer sets detected polymorphisms in the East Lansing (EL) reference population, the Compton (C) reference family, and between Line 63 and Line 72 chickens, respectively. The polymorphic microsatellite markers in the EL and C reference families were genetically mapped. Nine and seven mapped markers in the EL and C reference families, respectively, are polymorphic between Line 63 and Line 72, indicating that microsatellite markers will greatly enhance the ability to genotype specific loci of any chicken population. PMID- 8202434 TI - Satellite cell mitotic activity in posthatch turkey skeletal muscle growth. AB - The relationship between satellite cell mitotic activity and skeletal myofiber growth was examined in Pectoralis thoracicus and Biceps femoris muscles of Large White tom turkeys (Nicholas strain) at 3, 6, 9, 18, and 26 wk of age. Mitotically active satellite cells were labeled with 5-bromo-2'-deoxyuridine (BrdU). Labeled satellite cells were identified on enzymatically isolated myofiber segments using mouse anti-BrdU followed by fluorescein-5-isothiocyanate (FITC) conjugated goat anti-mouse IgG secondary antibodies. Myofiber nuclei (satellite cell nuclei + myonuclei) were counterstained with propidium iodide (PI). Myofiber segment diameter, myofiber segment length, and number of FITC- and PI-labeled nuclei were determined for each segment. At each age interval there was an increase in myofiber diameter, suggesting that the myofibers were growing during the entire experimental period. There was an age-related (P < .001) decrease in satellite cell mitotic activity and an age-related increase (P < .001) in the cytoplasmic volume to nucleus ratio (CNR) from 3 to 26 wk of age. An early phase of myofiber growth, between 3 and 6 wk of age, was characterized by a high level of satellite cell mitotic activity and increased CNR. Between 6 and 9 wk of age, satellite cell mitotic activity decreased, but the CNR showed no change (P > .05). During a late phase of myofiber growth, beyond 9 wk of age, satellite cell mitotic activity continued to decrease and myofiber growth occurred by an increased CNR. This study demonstrated that both Pectoralis thoracicus and Biceps femoris undergo a significant late phase of growth without appreciable production of myonuclei by satellite cell proliferation. PMID- 8202435 TI - A technique for cannulating the Cisterna magna and sampling cerebrospinal fluid from socially housed birds. AB - The measurement of central levels of neurochemicals is an important approach to the understanding of the neurophysiological basis of behavior patterns in animals. Previous studies have utilized central sampling techniques developed for individually housed animals. The purpose of this study was to develop a cannulation technique and a method for sampling cerebrospinal fluid (CSF) from socially housed birds to facilitate the study of the neurophysiological basis of social behaviors. The cannulation technique involved the surgical implantation of a 22-gauge concentric guide cannula into the cisterna magna of 16-wk-old, feed restricted male broiler breeders (n = 6). Individual-specific coordinates and optimum angle and depth of implantation of the cannula were determined in order to place the cannula correctly in the designated site. Once implanted, the guide cannula proved to be unobtrusive and secure and did not attract aggressive pecking from other birds in the pen. Two methods of CSF sampling were then examined. The first method required the use of a push-pull perfusion pump to withdraw CSF at a rate of 1 to 2 microL/min. The second method (passive), which did not use a pump, involved simply removing a "dummy" cannula from the guide cannula to release the CSF, which was then collected with a glass Hamilton syringe. Samples ranging from 100 to 500 microL were collected using the passive method. The combination of the cannulation technique described and the passive sampling method proved to be the most simple, efficient, and reliable method for measuring central levels of neurochemicals in socially housed broiler breeder males. PMID- 8202436 TI - Supercritical carbon dioxide extraction of lipids and cholesterol from dehydrated chicken meat. AB - Supercritical carbon dioxide (SC-CO2) extraction was studied for removal of lipids and cholesterol from dried chicken meat powder and chunks. Two combinations of pressure and temperature were used: 299 atm and 45 C, and 381 atm and 55 C, both providing a fluid density of .90 g/cm3. For a given quantity of CO2, at the higher temperature and pressure, significantly (P < .05) more lipids and cholesterol were extracted from the powder. At 381 atm and 55 C, approximately 89% of the lipids and 90% of the cholesterol were removed from the dehydrated chicken meat powder. With respect to the chunk chicken meat, about 93% of the lipids and 82% of the cholesterol were extracted at 299 atm and 45 C. It seemed that the SC-CO2 extraction process was more efficient when chunks were used. Protein was concentrated as cholesterol and lipids were removed by SC-CO2 extraction of both chicken meat types, and Hunterlab L values increased but aL values decreased, indicating a lighter color with less redness. This research indicated that SC-CO2 extraction holds promise for substantially reducing lipids and cholesterol in chicken meat. PMID- 8202437 TI - The effect of an acetic acid dip on carcass appearance, microbiological quality, and cooked breast meat texture and flavor. AB - In Experiment 1, broiler carcasses were subjected to a 10-min prechill treatment with and without a food grade vinegar at a concentration of .6% acetic acid. After treatment the carcasses were monitored for visual appearance and microbiological quality. Color change and skin appearance were subjectively monitored. Microbiological quality was determined using the low volume whole carcass rinse. Shear values of cooked muscle were determined using a Warner Bratzler attachment to an Instron. In a second experiment using the same treatment protocol, treated carcasses were chilled in an ice slush for 30 min and held overnight at 2 C. The breast muscles were removed and cooked by two methods. Triangle tests to determine sensory differences due to acetic acid were conducted. The skin color of treated carcasses turned a light yellow, and the feather follicles were protruded or puckered. Total aerobic counts were not affected by any of the treatments, but Enterobacteriaceae (ENT) counts of treated carcasses were significantly lower than the counts for the water control carcasses. Log10 ENT counts ranged from 4.51 for the control to 3.80 for the carcasses treated with acetic acid. Based on sensory triangle tests using a trained panel, there were no significant differences in the samples from either cooking method. PMID- 8202438 TI - The effect of acetic acid and air injection on appearance, moisture pick-up, microbiological quality, and Salmonella incidence on processed poultry carcasses. AB - Broiler carcasses were subjected to a 10-min prechill treatment with and without air injection and glacial acetic acid at concentrations of .3 and .6%. Some of the carcasses were inoculated with approximately 800 cells of a nalidixic acid resistant strain of Salmonella typhimurium 1 min prior to treatment. After treatment, the carcasses were monitored for their visual appearance, moisture pick-up, and microbiological quality. Appearance was subjectively monitored for color change and resulting skin texture. Microbiological quality was determined using the low volume whole carcass rinse, and moisture pick-up was determined by weight differences. The skin color of treated carcasses was light yellow and the feather follicles were protruded or puckered. Moisture pick-up was significantly reduced by the acid treatments. Total aerobes were not affected by any of the treatments, but Enterobacteriaceae (ENT) counts of treated carcasses were significantly lower than the counts for the water control carcasses. Log10 ENT counts ranged from 5.52 for the control to 4.48 for the air injection, and to a low of 2.93 for the air injection with .6% acetic acid. Salmonella incidence of inoculated carcasses was significantly reduced by the treatments. Using .6% acetic acid with air injection resulted in the greatest reduction in Salmonella incidence (8% positive). PMID- 8202439 TI - Feed gorging and extended water restriction do not produce knockdown in male turkeys fed monensin. AB - A study was conducted to determine the effects of feed restriction with subsequent gorging during extended water restriction on 27- to 57-d-old toms fed excess monensin. Four treatments were factorially arranged with two levels of dietary monensin (0 and 140 ppm) and two feeding-watering regimens (ad libitum and restricted). Ad libitum birds had full access to feed and water but restricted birds only had access to feed from 0800 to 1200 h daily. A 24-h water restriction regimen was imposed biweekly from 28 to 42 d and a 36-h water restriction regimen was imposed biweekly from 43 to 57 d. The restricted feeding and watering regimen decreased (P < .01) feed intake, weight gain, and feed efficiency. Excess monensin had no effect (P > .10) on feed intake regardless of feeding and watering regimen. Monensin had no effect on the weight gain and feed efficiency of ad libitum birds, but monensin exacerbated the decrease on gain (monensin by regimen, P < .01) and feed efficiency (monensin by regimen, P < .09) induced by feed and water restriction. No treatment-related abnormalities were observed during either interim or terminal necropsies. Neither clinical signs of ionophore toxicity nor pathologic findings attributed to monensin treatment were observed during the study. Based on these observations, feed gorging and water restriction will not adversely affect the health status of, or increase the mortality rate of, 4- to 8-wk-old male turkeys fed monensin. PMID- 8202440 TI - Boldo and boldine: an emerging case of natural drug development. AB - Boldo (Peumus boldus Mol.), a Chilean tree traditionally employed in folk medicine and recognized as a herbal remedy in a number of pharmacopoeias, mainly for the treatment of liver ailments, has recently been the subject of increasing attention. Boldine, in particular, the major and most characteristic alkaloidal constituent of this plant species, now emerges as its most interesting active principle from the pharmacological viewpoint. The recent demonstration that boldine is an effective antioxidant in both biological and non-biological systems has opened up the perspective of a broad range of uses in medicine and industry. Given the toxicological data on this alkaloid, its antioxidative properties situate it as a potentially useful substance in many disease states featuring free-radical related oxidative injury. This review attempts to cover and discuss the studies conducted over the last four decades on the chemical and pharmacological properties of boldo and its main constituent. PMID- 8202441 TI - Periaqueductal gray area and cardiovascular function. AB - The periaqueductal gray (PAG) area seems to play an important role in modulating several biological functions such as the triggering of stereotyped defence and reproductive behaviour, pain, anxiety and cardiovascular and respiratory activities. Anatomically this midbrain area is made up of symmetric neuronal columns arranged along the long axis of the aqueduct. In this paper we review the most important findings of the last 10-15 years about the interaction between the PAG area and the cardiovascular function. It is shown that these neuronal columns within the PAG area exhibit a viscerotropic organization which elicits both hypertensive and hypotensive responses. In particular, the stimulation of the ventral neuronal column evokes a hypotensive response associated with a regional decrease in the vascular resistance. On the contrary, the stimulation of the dorsal and lateral neuronal columns evokes arterial hypertension associated with specific changes of the vascular resistance. Recently the authors demonstrated that the glutamergic system in the PAG area (prevalently through NMDA subtype receptor) may also be involved in the control of cardiovascular system. Moreover, the involvement of the arginine vasopressin neuropeptide in the hypertension induced by administration of excitatory amino acids into the PAG area has been demonstrated. PMID- 8202442 TI - Effects of omeprazole on ethanol metabolism: an in vitro and in vivo rat and human study. AB - Since some H2-receptor antagonists, like cimetidine or ranitidine, affect ethanol metabolism by interference with gastric and/or hepatic alcohol dehydrogenase (ADH) it was investigated whether omeprazole has a similar effect and its effects were compared with those of cimetidine, an inhibitor of gastric ADH. The first pass metabolism (FPM), quantified by measuring the difference between areas under the curve (AUC) of ethanol blood concentrations after oral intake or intravenous administration of the same amount (0.3 g kg-1 b.w.) of ethanol (EtOH), was studied before and after 1 week of omeprazole (20 mg daily) or cimetidine (800 mg daily) administration in 10 normal male volunteers. ADH activity was determined in gastric mucosal samples, collected during endoscopy, before and after 1 month of omeprazole treatment. The effect of the drugs on gastric and hepatic ADHs was studied in vitro in both rat and man. No significant effect of omeprazole was found on AUCs of the blood EtOH concentrations. The ADH activity in antral mucosa before and after omeprazole therapy did not show significant differences. In vitro, omeprazole reduced the activity of the low Km gastric ADH with a Ki of 5.6 mM in rat and the hepatic ADH activity with a Ki of 2.4 mM in man, whereas the drug did not show any effect on hepatic ADH in rat and gastric ADH in man. On the contrary, cimetidine increased the AUCs of EtOH blood concentrations after both gastric and intravenous route and, in the in vitro assay, inhibited gastric and hepatic ADH in both man and rat. These results indicate that omeprazole does not affect EtOH metabolism in man and seems to be safer than cimetidine in subjects unable to reduce ethanol intake during the therapy for peptic ulcer or other hypersecretory conditions. PMID- 8202443 TI - Antimicrobial activity of 5-substituted-3-amino-1,2,4-triazoles. AB - Some dyes derived from 3-amino-5-(ortho, meta, and para-pyridyl)-1,2,4-triazoles were tested for antimicrobial activity. 13 compounds showed anti-staphylococcal activity and one had anti-candida activity. Some substances had antimicrobial activity only after light irradiation. PMID- 8202444 TI - Atherosclerotic lesion development in hypercholesterolemic Japanese quail following probucol treatment: a biochemical and morphologic evaluation. AB - Probucol, a cholesterol-lowering agent which possesses antioxidant properties, was evaluated in hypercholesterolemic Japanese quail in order to assess the significance of antioxidant therapy on the development of atherosclerosis. Forty quail were fed a 0.5% cholesterol diet containing 0, 100, 200 or 500 mg kg-1 probucol for 2 months. At necropsy, plasma total and lipoprotein cholesterol and lipoprotein distribution were unchanged despite plasma probucol levels of 50 to 59 micrograms ml-1. The cholesteryl ester content of the liver and blood vasculature (brachiocephalic artery and aortic arch combined) was reduced by 33% and 62%, respectively, in animals given 500 mg kg-1 probucol. The vascular free cholesterol content was also reduced by 43 to 60% over the probucol dose range. Morphometric analysis of the brachiocephalic artery revealed that probucol reduced the incidence of lesions containing esterase-positive cells from 62% in untreated animals to 26% and 13% in animals administered 200 and 500 mg kg-1 probucol, respectively. No difference in mean wall thickness or area of the bracheocephalic artery was noted between the groups. Thus, we conclude that probucol can blunt the cholesteryl ester and macrophage enrichment of atherosclerotic lesions and this activity appears to be mediated by the compound's antioxidant properties since the changes noted were seen in the absence of alterations in plasma total and lipoprotein cholesterol levels. PMID- 8202445 TI - Influence of chronic captopril therapy on the mechanical performance of the infarcted rat heart. AB - The influence of angiotensin converting enzyme inhibition of hemodynamic changes, development of postinfarction myocardial hypertrophy and left ventricular performance was studied in rats. Infarction was produced under ether anaesthesia by ligature of the descending anterior branches of the left coronary artery. Control rats were submitted to a sham surgery. Groups of infarcted (Inf) and sham operated control (SO) animals were daily treated with intraperitoneal injections of captopril (Cap, 30 mg kg-1) or saline (Sal) for 4-5 weeks. This Cap dose produced a similar decrease in arterial blood pressure in Inf and SO animals. The intraventricular pressures measured in anaesthetized rats showed a marked elevation in the right ventricular systolic (38 +/- 4 mmHg) and end diastolic (4 +/- 1 mmHg) pressures in the Inf group compared with the SO group (24 +/- 1 mmHg and 1 +/- 0.4 mmHg, respectively). Cap did not change the pressure overload in the right ventricle. In the left ventricle, however, the end diastolic pressure of the Inf group under Cap was significantly reduced in relation to Sal (12 +/- 3 mmHg and 19 +/- 2 mmHg, respectively, P < 0.05). The post infarction myocardial hypertrophy was depressed by Cap only in the right heart chambers. Thus the right ventricular weight to body weight ratio (mg/g) increased from 0.56 +/- 0.03 in the SO-Sal group to 0.96 +/- 0.07 (P < 0.05) in the Inf-Sal group and decreased to 0.73 +/- 0.04 (P < 0.05) in the Inf group under Cap. The infarction-induced hypertrophy of the left heart chambers was unaffected by Cap. Left ventricular function was assessed in the hearts perfused in vitro according to the Langendorff technique. The peak isovolumic systolic pressure (ISP) developed at different diastolic pressures (0-30 mmHg) and Ca2+ concentrations (0.62 and 1.25 mM) was measured. The ISP and the positive inotropic response to Ca2+ was similarly depressed in both groups of infarcted hearts. Thus the chronic administration of Cap to Inf rats reduces the left ventricular filling pressure but does not reduce the postinfarction pulmonary hypertension. Despite this latter finding, Cap therapy was able to significantly reduce the post-infarction hypertrophy in both right heart chambers. Cap therapy did not change significantly left ventricular systolic function and Ca2+ responsiveness of the myocardium surviving to infarction. PMID- 8202446 TI - Effects on intestinal microflora, gastrointestinal tolerability and antiinflammatory efficacy of diclofenac and nitrofenac in adjuvant arthritic rats. AB - Since it is known that nitric oxide plays an important protective role in maintaining the tissue integrity and is cytotoxic for invasive micro-organisms, diclofenac and a new original diclofenac-derivate, nitrofenac (containing the nitric oxide group), was administered at doses of 0.3 and 3 mg kg-1 per os to adjuvant arthritic rats. At the 14th, 21st and 28th days after arthritis induction, the antiinflammatory efficacy and the effects on intestinal microflora of the two drugs were evaluated; moreover, at the end of the study period, the gastrointestinal tract was examined macroscopically for any presence of lesions. Daily oral administration of diclofenac and nitrofenac at 3 mg kg-1 markedly and significantly inhibited arthritis development until the end of the study period. Some significant changes were observed in anaerobic and Gram-negative bacterial flora, particularly the total disappearance, in all treated rats, of Escherichia coli 1, also 7 days after the last drug administration. Finally, no ulcers or severe damage were observed macroscopically with either drug, even if some alterations in the mucosa and haemorrhagic effusions were more evident in rats treated with diclofenac at 3 mg kg-1. In conclusion, in this chronic model a similar therapeutic efficacy of diclofenac and nitrofenac is shown in arthritic rats. The better gastrointestinal tolerability observed in nitrofenac-treated rats could be attributed to the release of nitric oxide. PMID- 8202447 TI - Fluorescence-activated cell sorting-derived clones of Babesia bigemina show karyotype polymorphism. AB - Use of the fluorescence-activated cell sorter proved to be an accurate and highly efficient means for cloning Babesia parasites. These qualities were examined by separating a mixed population of Babesia-infected bovine erythrocytes composed of two isolates with different karyotypes. Direct evidence of polymorphism was detected during comparison of the resultant clones. PMID- 8202448 TI - Effects of Nosema algerae infections on the gene activity of the salivary gland chromosomes of Acricotopus lucidus (Diptera, Chironomidae). AB - Larvae of Acricotopus lucidus (Diptera, Chironomidae) were successfully infected with Nosema algerae (Microsporidia, Nosematidae). Treatment of newly hatched larvae with 2-3 x 10(5) spores/ml produced a 59.7%-83.8% rate of microsporidia infected animals within 6 weeks. One of the host tissues infected was the polytene salivary gland; 31.3%-35.3% of the larvae showed infections in the gland cells. This made it possible to investigate the reaction of the puffing pattern of the polytene host-cell chromosomes to the presence of an intracellular parasite. In slightly or moderately infected salivary gland cells, no change in the regular puffing patterns was observed. Only in heavily infected cells did an inactivation of cell-type-specific Balbiani rings and puffs occur, resulting in a change in the cell-type-specific genetic programme. PMID- 8202449 TI - Cell-to-cell interactions suggesting a sexual process in Herpetomonas megaseliae (Kinetoplastida: Trypanosomatidae). AB - Giemsa-stained smears of Herpetomonas megaseliae cultures in LIT medium displayed on several occasions not only the typically dividing promastigotes but also pairs of apposed parasites attached by their posterior ends, where a cellular enlargement and a ring-like border generally occurred; other pairs formed by an elongated promastigote and a bell-shaped cell were also found. In both cases, either each of the joined cells could have its own nucleus or one of them was anucleate and the other presented two nuclei that were sometimes so close that they appeared to be a single nucleus. These findings, along with others seeming to be intermediate steps between them, strongly suggested that a sexual process, involving parasite union followed by nuclear migration from one cell to the other and then by fusion, was taking place in such cultures. PMID- 8202450 TI - Ultrastructural localisation of FMRFamide- and pancreatic polypeptide immunoreactivities within the central nervous system of the liver fluke, Fasciola hepatica (Trematoda, Digenea). AB - A post-embedding immunogold technique was used to examine the subcellular distribution of immunoreactivities to the invertebrate peptide, FMR-Famide, and to vertebrate pancreatic polypeptide (PP) within the central nervous system of the trematode, Fasciola hepatica. Gold labeling of peptide was localised exclusively over both dense-cored and ellipsoidal electron-dense vesicles (with a homogeneous matrix) present within nerve cell bodies, small and 'giant' nerve processes of the neuropile in the cerebral ganglia and transverse commissure, as well as in the main longitudinal nerve cords. Double labeling demonstrated an apparent co-localisation of FMRFamide and PP immunoreactivities in the same dense cored vesicles, although populations of ellipsoidal electron-dense vesicles that labeled solely for FMRFamide were also evident. Antigen pre-absorption studies indicated little, if any, cross-reactivity of the two antisera. PMID- 8202451 TI - Effect of the strain of Toxoplasma gondii on the development of toxoplasmic encephalitis in mice treated with antibody to interferon-gamma. AB - To examine whether differences observed in the development of toxoplasmic encephalitis between strains of Toxoplasma gondii are determined by the numbers of cysts occurring in the brain, C57BL/10 mice were infected with ten cysts of the ME49, Beverley, or C56 strain of the parasite. At 10 weeks after infection, the numbers of cysts and inflammatory changes in the brains of the mice were examined in each of the experimental groups. The ME49 strain formed significantly more cysts than did the other two strains, with no difference in the number of cysts being noted between the Beverley and C56 strains. Mice infected with the ME49 strain showed infiltration of inflammatory mononuclear cells in both the meninges and the parenchyma of their brains, whereas mice infected with the Beverley or C56 strain showed no inflammatory changes in their brains. Treatment of mice with a monoclonal antibody to interferon-gamma (IFN-gamma) once weekly for 3 weeks beginning at 10 weeks after infection augmented the inflammatory changes in the brains of mice infected with each strain. However, the intensity of the inflammatory changes differed significantly between the mice, depending on the strain of T. gondii with which they were infected. Mice infected with the ME49 strain showed the most remarkable inflammatory changes in their brains. Mice infected with the Beverley strain developed foci of acute inflammation in their brains after treatment with an antibody to IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202453 TI - Light microscopic and three-dimensional morphology of the human muscular sarcocyst. AB - Established criteria for morphological typing of sarcocysts was applied to a large series of cases of human skeletal muscle sarcocystosis in Malaysia to determine the type of sarcocyst present. We also wanted to test the general usefulness of this classification and to determine if there are any new cyst types. Three-dimensional (3-D) reconstruction was done to see if the sarcocyst has a distinct 3-D morphology. A total of 66 sarcocysts from 21 cases of human muscle sarcocystosis obtained from a previous prevalence study were examined. Tissue sections (5 microns thick) were stained with haematoxylin and eosin and studied under the light microscope. For 3-D reconstruction, an image analyser was used to align and reconstruct the sarcocyst after microscopic images had been captured with a charge-coupled device (CCD) camera. All the cysts best fit into the type 4 category. This classification is generally useful, although cyst wall characteristics and zoite size appear to be the most reliable criteria for classification. The cyst width averaged 77 microns (range, 30-137.5 microns). Cyst walls were smooth, had no cytophaneres and were less than 1 micron thick. No secondary cyst wall or surrounding inflammation was evident. Numerous cyst merozoites with diameters averaging 1 micron filled the cyst lumen. Although septa were not apparent, in many cysts, zoites were arranged in a unique, curvilinear fashion that suggested their presence. 3-D reconstruction showed the sarcocyst to be a long, tortuous "cylinder" with no branching or other distinguishing feature. PMID- 8202452 TI - Morphology of Blastocystis sp. from domestic birds. AB - A study of Blastocystis sp. from domestic birds was undertaken to determine if morphological differences occurred. Fresh faecal material from domestic chickens, ducks and geese and from commercially farmed ostriches was obtained. Blastocystis sp. from chickens was morphologically very different from that from the other hosts, having within the nucleus discrete spots of chromatin rather than a crescentic band (ducks and geese) or an elliptical band (ostrich). A thick surface coat surrounded all Blastocystis sp. cells in the faecal material, with isolates from the ostrich having the thickest surface coat relative to the cell diameter. Cysts were more commonly found in the chicken samples but were also detected in the duck and ostrich samples. This study suggests that three morphologically distinct groups are represented: one in the chicken, one in the ostrich and another in ducks and geese. These tentative conclusions require confirmation by molecular techniques. PMID- 8202454 TI - Morphological and genetic comparison of two Proteocephalus species (Cestoda: Proteocephalidae). AB - Two Proteocephalus species, P. neglectus La Rue, 1911 and P. exiguus La Rue, 1911, parasites of salmonid and coregonid fishes, were compared morphologically, biometrically, and electrophoretically. The study revealed that the two taxa cannot be differentiated by the morphological criteria used. No fixed allelic difference was found. In all, 12 of 13 enzymes detected by isoelectric focusing exhibited virtually identical isoenzyme profiles in both species. Only in the glutamate oxaloacatate transaminase enzyme locus was a difference observed. The negligible differences in zymograms and morphology, including similar biometric variability of the taxa studied, suggest that the species could be conspecific. PMID- 8202455 TI - Trypanocidal activity of a myristic acid analog in axenic cultures of Trypanosoma evansi. AB - The growth of bloodstream forms of Trypanosoma evansi in axenic culture was inhibited by incubation with 11-oxatetradecanoic acid (O-11), an analog of myristic acid. Parasites isolated from Asia, Africa and South America were affected to a similar extent in measurements using three different assay systems concerned with different aspects of trypanosome growth and metabolism. The concentration of O-11 that inhibited trypanosome growth by 50% (LD50) was 3.7 +/- 0.2 microM as measured by direct counting of survivors using a haemocytometer, 5.1 +/- 2.0 microM in a colorimetric test based on the formation of a formazan product, and 8.8 +/- 3.7 microM by estimation of pyruvate. The activity of the drug was enhanced by the addition of fatty-acid-free bovine serum albumin as a carrier protein to the culture medium at an optimal concentration of 5 mg/ml. Increasing amounts of the donor horse serum used for routine maintenance of these cultures, which is normally the only source of myristic acid for these trypanosomes, also affected the toxicity of the drug, in this case increasing the LD50. PMID- 8202457 TI - Synchronization of Plasmodium yoelii nigeriensis and P. y. killicki infection in the mouse by means of Percoll-glucose gradient stage fractionation: determination of the duration of the schizogonic cycle. AB - The youngest (rings and young trophozoites) erythrocytic stages of Plasmodium yoelii nigeriensis and P. yoelii killicki, two rodent malaria subspecies developing very asynchronously in the blood, were separated from the other stages using a discontinuous Percoll-glucose gradient. They were inoculated into mice and the subsequent infection remained synchronous for two generations. The duration of the asexual cycle was found to be 18 h. PMID- 8202456 TI - A model system for the study of antigen secretion by adult Schistosoma mansoni in vivo. AB - Schistosoma mansoni (6 weeks old) were surgically transferred from donor C57BI/6 mice to the hepatic portal veins of naive recipients of the same inbred strain. Between 70% and 100% of the parasites were alive 15 days later, and egg deposition was observed after transfer of worm pairs. The physiological status of the parasites was monitored by measuring the levels of a schistosome gut antigen, circulating anodic antigen (CAA), in the serum of the recipients. When only male worms were transferred, serum CAA levels increased slowly to a peak 9 days later, which was followed by a rapid decline. When worm pairs were transferred, there was an early peak in serum CAA levels followed by a gradual decline, but these levels were always higher than those recorded after male-only transfer; in two mice the pattern was similar to that observed following receipt of male worms. More CAA and eggs were produced after transfer of paired versus separated worms. It was concluded that although worm pairs can be successfully transferred, their physiological status may be sub-optimal. In contrast, male worms survive consistently well, and their transfer to a naive recipient provides a convenient model with which to study the release of antigens by schistosomes in vivo. PMID- 8202458 TI - Detection of metabolic enzymes of Eimeria by ampholine-polyacrylamide gel isoelectricfocusing. PMID- 8202459 TI - A concentration of tegumental papillae in the pharynx of Zygocotyle lunata (Trematoda: Paramphistomidae). PMID- 8202460 TI - Codon usage and gene organization in Brugia. PMID- 8202461 TI - Endocytosis at the micropore of Toxoplasma gondii. AB - Ultrastructural studies were undertaken to reexamine the structure and function of the micropore of Toxoplasma gondii. By incubating tachyzoites with the tracer horseradish peroxidase (HRP), we showed for the first time cytochemically that an extracellular tracer was internalized into vacuoles at the micropore. Our morphological observations also demonstrated that the base of the micropore in both tachyzoites and bradyzoites was sometimes covered by a clathrin-like bristle coat. A coated vesicle was observed in continuity with a bradyzoite micropore, and large (150-nm) coated vesicles were occasionally present just beneath the micropore. These results suggest that receptor-mediated endocytosis occurs at the micropore. In other micrographs, however, the micropore appeared uncoated. In some bradyzoites, the uncoated micropore was greatly dilated, and it contained vesicles like those found in the cyst matrix associated with debris from disintegrated parasites. We had previously observed such debris from fragmented organisms in cysts prepared in vivo. These results indicate that residues from dead bradyzoites may provide nutrients for younger, developing parasites in the same cysts. Our observations also suggest that either receptor-mediated or bulk endocytosis can occur at the micropore, perhaps depending upon the availability of specific ligands. Investigation of a receptor-mediated pathway may reveal a means for targeting therapy selectively to the parasites to benefit patients with disseminated toxoplasmosis. PMID- 8202462 TI - Infection course of the strobilar stage of Taenia crassiceps in golden hamsters, with reference to host responses. AB - The time course of intestinal infection of golden hamsters (Mesocricetus auratus) with Taenia crassiceps was monitored every 2 days up to day 26 postinfection (p.i.). The isolate used was originally obtained from Clethrionomys rutilus on St. Lawrence Island, Bering Sea (USA), and shows a high level of enteral establishment without parenteral infection. Following oral administration of various numbers (3, 15, 30, or 60) of metacestodes, proportional numbers of cestodes attached their scolices to the mucosa of the middle (one-third) segment of the small intestine. Except for animals given 3 metacestodes, dislocation of cestodes to the posterior parts of the intestine was noted on days 10-14 p.i. and began faster in animals that had received larger numbers of metacestodes. Concurrent with dislocation or elimination of cestodes, there existed distinct increases in intestinal eosinophil peroxidase and myeloperoxidase activities. The number of mast cells in the lamina propria peaked on day 16 p.i., and specific serum IgG began to increase within 1 week p.i. The level of all these changes was dose-dependent. In prednisolone-treated animals that received 60 metacestodes, dislocation of cestodes was not evident, and mucosal inflammatory changes were suppressed to a considerable extent. The findings of this study are discussed as a model for the study of canine taeniasis. PMID- 8202463 TI - Molecular dynamics studies on mutants of Cu,Zn superoxide dismutase: the functional role of charged residues in the electrostatic loop VII. AB - Molecular dynamics (MD) calculations have been performed on mutants of superoxide dismutase (SOD) on some residues present in the electrostatic loop. These calculations have provided the solution structures for the mutants Thr-137-->Ile and Arg; Lys-136-->Ala; Glu-132-->Gln; Glu-133-->Gln; Glu-132, Glu-133-->Gln-132, Gln-133 and-->Gln-132, Lys-133. The structural and dynamic properties of these mutants have been correlated with the catalytic properties and available spectroscopic data. The water molecule present in the active site close to the copper ion in wild type (WT) SOD is missing in the MD average structure of the Thr-137-->Ile mutant, while this molecule is present in the MD average structures of all the other mutants and of WT SOD. This agrees with the experimental data. This is an important result that shows the validity of our calculations and their ability to reproduce even subtle structural features. Addition of one or more positive charges on the 132 and/or 133 positions does not sizably perturb the structure of the active site channel, while the introduction of a positively charged residue (Arg) on position 137 has a large effect on the structure of the electrostatic loop. Analysis of the MD average structures of these mutants has pointed out that the simple electrostatic effects of charged residues in the channel are not the only factor relevant for enzymatic behavior but that the structure of the electrostatic loop and the location of the charged residues also contribute to the catalytic properties of SOD. PMID- 8202464 TI - Treatment of electrostatic effects in proteins: multigrid-based Newton iterative method for solution of the full nonlinear Poisson-Boltzmann equation. AB - The nonlinear Poisson-Boltzmann equation (NPBE) provides a continuum description of the electrostatic field in an ionic medium around a macromolecule. Here, a novel approach to the solution of the full NPBE is developed. This robust and efficient algorithm combines multilevel techniques with a damped inexact Newton's method. The CPU time required for solution of the full NPBE, which is less than that for standard single-grid approaches in solving the corresponding linearized equation, is proportional to the number of unknowns enabling applications to very large macromolecular systems. Convergence of the method is demonstrated for a variety of protein systems. Comparison of the solutions to the linearized Poisson Boltzmann equation shows that the damping of the electrostatic field around the charge is increased and that the potential scales logarithmically with charge. The inclusion of the full nonlinearity thus reduces the impact of highly charged residues on protein surfaces and provides a more realistic representation of electrostatic effects. This is demonstrated through calculation of potential around the active site regions of the 1,266-residue tryptophan synthase dimer and in the computation of rate constants from Brownian dynamics calculations in the superoxide dismutase-superoxide and antibody-antigen systems. PMID- 8202465 TI - Thermodynamics of ubiquitin unfolding. AB - The energetics of ubiquitin unfolding have been studied using differential scanning microcalorimetry. For the first time it has been shown directly that the enthalpy of protein unfolding is a nonlinear function of temperature. Thermodynamic parameters of ubiquitin unfolding were correlated with the structure of the protein. The enthalpy of hydrogen bonding in ubiquitin was calculated and compared to that obtained for other proteins. It appears that the energy of hydrogen bonding correlates with the average length of the hydrogen bond in a given protein structure. PMID- 8202466 TI - An improved pair potential to recognize native protein folds. AB - We present a novel method to improve a simple pair potential of mean force, derived from experimentally determined protein structures, in such a way that it recognizes native protein folds with high reliability. This improvement is based on the use of mutation data matrices to overcome difficulties arising from the poor statistics of small sample sizes. A set of 167 protein chains taken from the Brookhaven Protein Structure Data Base, selected from high-resolution structures and avoiding homologous proteins, is used for generation of the potential set. The potential describes interresidue pair energies depending on distance and sequential separation, and is calculated using the Boltzmann equation. Its performance is evaluated by jackknife tests that try to identify the native fold for a given sequence among a large number of possible threadings on all structures in the set without allowing for gaps. Up to 94% of the protein chains are correctly assigned to their native folds, so that all proper single-chain domains are recognized. PMID- 8202467 TI - Hydrogen bond strength and beta-sheet propensities: the role of a side chain blocking effect. AB - Amino acid side chains can enhance peptide group hydrogen bond strength in protein structures by obstructing the competing hydrogen bond to solvent in the unfolded state. Available data indicate that the steric blocking effect contributes an average of 0.5 kJ per residue to protein hydrogen bond strength and accounts for the intrinsic beta-sheet propensities of the amino acids. In available data for helical models, the contribution to alpha-helix propensities is obscured especially by large context-dependent effects. These issues are all related by a common side chain-dependent steric clash which disfavors peptide to water H-bond formation, peptide to catalyst complexation in hydrogen exchange reactions (Bai et al., Proteins 17:75-86, 1993), and peptide to peptide H-bonding in the helical main chain conformation (Creamer and Rose, Proc. Natl. Acad. Sci. U.S.A. 89:5937-5941, 1992) but not in beta-strands. PMID- 8202468 TI - A simplified amino acid potential for use in structure predictions of proteins. AB - A simplified description and a corresponding force field for polypeptides is introduced. Each amino acid residue is reduced to one interaction site, representing the backbone, and one or two side chain sites depending on its size and complexity. Site-site interactions are parameterized after a hydrophobicity criterium. The treatment of backbone sites is in addition designed to reproduce typical polypeptide hydrogen bonding patterns, as well as yielding conformations in accord with the allowed phi and psi angles through an effective angle potential. There are no explicit charges in the model. The derived energy functions, which are based on thermodynamic data and sterical consideration of allowed backbone conformations, correspond to the introduction of an effective potential. The model is tested on two small proteins, avian pancreatic polypeptide and a parathyroid hormone-related protein, by simulating folding from an initially extended state using Monte Carlo methods. The reduced amino acid description is able to satisfactorily reproduce the experimentally determined native structures. PMID- 8202469 TI - A method for alpha-helical integral membrane protein fold prediction. AB - Integral membrane proteins (of the alpha-helical class) are of central importance in a wide variety of vital cellular functions. Despite considerable effort on methods to predict the location of the helices, little attention has been directed toward developing an automatic method to pack the helices together. In principle, the prediction of membrane proteins should be easier than the prediction of globular proteins: there is only one type of secondary structure and all helices pack with a common alignment across the membrane. This allows all possible structures to be represented on a simple lattice and exhaustively enumerated. Prediction success lies not in generating many possible folds but in recognizing which corresponds to the native. Our evaluation of each fold is based on how well the exposed surface predicted from a multiple sequence alignment fits its allocated position. Just as exposure to solvent in globular proteins can be predicted from sequence variation, so exposure to lipid can be recognized by variable-hydrophobic (variphobic) positions. Application to both bacteriorhodopsin and the eukaryotic rhodopsin/opsin families revealed that the angular size of the lipid-exposed faces must be predicted accurately to allow selection of the correct fold. With the inherent uncertainties in helix prediction and parameter choice, this accuracy could not be guaranteed but the correct fold was typically found in the top six candidates. Our method provides the first completely automatic method that can proceed from a scan of the protein sequence databanks to a predicted three-dimensional structure with no intervention required from the investigator. Within the limited domain of the seven helix bundle proteins, a good chance can be given of selecting the correct structure. However, the limited number of sequences available with a corresponding known structure makes further characterization of the method difficult. PMID- 8202470 TI - Cyanomet human hemoglobin crystallized under physiological conditions exhibits the Y quaternary structure. AB - Cyanomet human hemoglobin has been crystallized at a chloride ion concentration and pH similar to physiological conditions. Molecular replacement calculations definitively show that the hemoglobin subunits are arranged in the Y quaternary form recently discovered in carbon monoxy hemoglobin Yp-silanti (beta 99 Asp Tyr), and subsequently observed in carbon monoxy normal human hemoglobin crystallized at low ionic strength and low pH. The structure has been refined at 2.09 A resolution to an R-value of 0.232, and further refinement is currently underway. Although the refinement is not yet complete, our results are the first indication that the Y structure may represent an important quaternary form of liganded hemoglobin under physiological buffer conditions. These results suggest the need for a reexamination of structure-function correlations in the hemoglobin system. PMID- 8202471 TI - Crystallization and preliminary crystallographic studies of the precursor and mature forms of a neutral lipase from the fungus Rhizopus delemar. AB - A neutral lipase from the filamentous fungus Rhizopus delemar has been crystallized in both its proenzyme and mature forms. Although the latter crystallizes readily and produces a variety of crystal forms, only one was found to be suitable for X-ray studies. It is monoclinic (C2, a = 92.8 A, b = 128.9 A, c = 78.3 A, beta = 135.8) with two molecules in the asymmetric unit related by a noncrystallographic diad. The prolipase crystals are orthorhombic (P2(1)2(1)2(1), with a = 79.8 A, b = 115.2 A, c = 73.0 A) and also contain a pair of molecules in the asymmetric unit. Initial results of molecular replacement calculations using the refined coordinates of the related lipase from Rhizomucor miehei identified the correct orientations and positions of the protein molecules in the unit cells of crystals of both proenzyme and the mature form. PMID- 8202472 TI - Genetic instability of plant tissue cultures: breakdown of normal controls. AB - Plants regenerated from relatively undifferentiated callus cultures possess a vast array of genetic changes. Such variations can result in useful agricultural and horticultural products. For other purposes, however, variations in traits other than those of interest may be undesirable--for example, using cultured cells for genetic engineering. Any steps made toward understanding the basis of tissue culture-induced genetic variation should be helpful in developing a more stable and manipulatable somatic cell system. This review provides a glimpse at the specific kinds of genetic changes encountered among regenerated plants and their progeny. Included among these variations are cytosine methylation alterations of the genome. The repeat-induced point mutation (RIP) phenomenon, reported for filamentous fungi, is invoked to provide a framework to consider the origin of variation in plant tissue cultures. PMID- 8202473 TI - Human giant cell tumors of the bone (osteoclastomas) are estrogen target cells. AB - The decrease in estrogen levels that follows the onset of menopause results in rapid bone loss and osteoporosis. The major effect of estrogen deficiency on bone metabolism is an increase in the rate of bone resorption, but the precise mechanism by which this occurs remains unresolved. A recently developed technique for the isolation of avian osteoclasts has been modified to obtain highly purified multinucleated cells from human giant cell tumors. These osteoclast-like cells have been examined for evidence of estrogen receptors (ERs) and responses to 17 beta-estradiol (17 beta-E2). Analysis of giant-cell RNA demonstrated expression of ER mRNA. Furthermore, immunoblot analysis revealed that the giant cells contained a 66-kDa protein that was recognized by a monoclonal antibody specific for the human ER. When isolated multinucleated cells were cultured on slices of bone, there was a dose-dependent decrease in resorption in response to treatment detectable at 10 pM 17 beta-E2. Treatment with 10 nM 17 alpha-estradiol or vehicle (control) did not inhibit resorption. Moreover, the multinucleated cells isolated from these tumors had decreased mRNA levels for cathepsin B, cathepsin D, and tartrate-resistant acid phosphatase (TRAP) as well as secreted cathepsin B and TRAP enzyme activity in response to treatment with 10 nM 17 beta E2. In contrast to these data, no change in gene expression was detected in mononuclear cells from these tumors in response to 17 beta-E2 treatment. These data support the proposition that human osteoclasts are target cells for estrogen and that estrogen can inhibit bone resorption by human osteoclasts. PMID- 8202474 TI - Molecular cloning of an essential subunit of RNA polymerase II elongation factor SIII. AB - A transcription factor designated SIII was recently purified from mammalian cells and shown to regulate the activity of the RNA polymerase II elongation complex. SIII is a heterotrimer composed of approximately 110-, 18-, and 15-kDa polypeptides and is capable of increasing the overall rate of RNA chain elongation by RNA polymerase II by suppressing transient pausing of polymerase at multiple sites on the DNA template. Here we describe the molecular cloning and characterization of a cDNA encoding the functional 15-kDa subunit (p15) of SIII. The p15 cDNA encodes a 112-amino-acid polypeptide with a calculated molecular mass of 12,473 Da and an electrophoretic mobility indistinguishable from that of the natural p15 subunit. When combined with the 110- and 18-kDa SIII subunits, bacterially expressed p15 efficiently replaces the natural p15 subunit in reconstitution of transcriptionally active SIII. A homology search revealed that the amino-terminal half of the SIII p15 subunit shares significant sequence similarity with a portion of the RNA-binding domain of Escherichia coli transcription termination protein rho and with the E. coli NusB protein, suggesting that SIII may be evolutionarily related to proteins involved in the control of transcription elongation in eubacteria. PMID- 8202475 TI - The cooperativity and allosteric inhibition of Escherichia coli phosphofructokinase depend on the interaction between threonine-125 and ATP. AB - During the reaction catalyzed by the phosphofructokinase (EC 2.7.1.11) from Escherichia coli, the phosphoryl group transferred from ATP interacts with Thr 125 [Shirakihara, Y. & Evans, P. R. (1988) J. Mol. Biol. 204, 973-994]. The replacement of Thr-125 by serine changes the saturation by fructose 6-phosphate from cooperative to hyperbolic and abolishes the allosteric inhibition by phosphoenolpyruvate. The same changes, a saturation by fructose 6-phosphate that is no longer cooperative and an activity that is no longer inhibited by phosphoenolpyruvate, are observed with wild-type phosphofructokinase when adenosine 5'-[gamma-thio]triphosphate is used instead of ATP as the phosphoryl donor. These two perturbations of the ATP-Thr-125 interaction lead to the suppression of both the allosteric inhibition by phosphoenolpyruvate and the cooperativity of fructose-6-phosphate saturation, as if replacing the neutral oxygen of ATP by sulfur or removing the methyl group of Thr-125 had "locked" phosphofructokinase in its active conformation. The geometry of this ATP-Thr-125 interaction and/or the presence of the methyl group on the beta-carbon of Thr-125 are crucial for the regulatory properties of phosphofructokinase. This interaction could be a hydrogen bond between the neutral oxygen of the gamma phosphate of ATP and the hydroxyl group of Thr-125. PMID- 8202476 TI - Herpes simplex virus 1 gamma(1)34.5 gene function, which blocks the host response to infection, maps in the homologous domain of the genes expressed during growth arrest and DNA damage. AB - The gamma(1)34.5 gene of herpes simplex virus is dispensable in some cell lines (e.g., Vero). In others (e.g., human neuroblastoma cell line SK-N-SH), the gamma(1)34.5- deletion mutant triggers a premature total shutoff of all protein synthesis, thereby rendering the cell nonviable and reducing drastically viral yields. The inability to prevent the cellular stress response that causes the infected cell to die may be responsible for the inability of the deletion mutant to multiply and cause pathology in the central nervous system of mice. The gamma(1)34.5 gene consists of an amino-terminal domain, a variable linker sequence consisting of 3 amino acids repeated 5-10 times, and a carboxyl-terminal domain homologous to the corresponding domain of MyD116, a gene expressed in myeloid leukemia cells induced to differentiate by interleukin 6, and growth arrest and DNA damage gene 34 (GADD34), a gene induced by growth arrest and DNA damage. We have constructed several viral mutants from which various domains of the gamma(1)34.5 gene had been deleted or rendered mute by the insertion of a stop codon. Studies on those mutants show that the domain of the gamma(1)34.5 gene necessary to preclude the total shutoff of protein synthesis corresponds to the carboxyl-terminal domain of the gamma(1)34.5 gene homologous to the corresponding coding domain of the MyD116 and GADD34 genes. PMID- 8202477 TI - Platelet-activating factor and retinoic acid synergistically activate the inducible prostaglandin synthase gene. AB - Platelet-activating factor (PAF), a potent lipid mediator generated in cell injury and in the inflammatory and immune responses, promotes transcriptional activation of several primary response genes. TIS10/PGS-2 is a primary response gene encoding the inducible form of prostaglandin synthase. The inductive effects of PAF and retinoic acid (RA), alone and in combination, were studied with the regulatory region of TIS10/PGS-2 transfected into an exponentially growing glioblastoma-neuroblastoma NG108-15 hybrid in the human SH-SY5Y neuroblastoma or in the NIH 3T3 cell. RA alone exhibited only a small inductive effect. However, in the presence of RA (100 nM), a PAF-dependent (1-50 nM) synergistic activation of luciferase reporter constructs driven by regulatory regions of the TIS10/PGS-2 gene was found. The hetrazepine BN-50730, an antagonist selective for intracellular PAF binding sites, inhibited PAF and RA induction of luciferase from the TIS10/PGS-2 promoter. Thus, the intracellular PAF binding site is involved in TIS10/PGS-2 expression. Induction is rapid, suggesting that the combination of PAF and RA activates a preexisting latent transcription factor(s). Deletion studies restrict the major PAF and RA cis-acting response element of the TIS10/PGS-2 gene to a 70-nucleotide sequence as an intracellular inducer of TIS10/PGS-2 expression. The synergistic effect of RA and PAF represents an unusual convergence of nuclear signaling pathways by which, through the modulation of preexisting transcription factors, specific gene expression can be upregulated. PAF-dependent induction of TIS10/PGS-2 expression may play a role in cell injury, differentiation, inflammation, and immune responses. PMID- 8202478 TI - Circadian expression of the luciferin-binding protein correlates with the binding of a protein to the 3' untranslated region of its mRNA. AB - The circadian-expressed luciferin-binding protein from the dinoflagellate Gonyaulax polyedra is regulated at the translational level. We detected a protein, apparently a dimer, that binds specifically to the 3' untranslated region of its mRNA. Its binding site was localized within a 22-nt region in the 3' untranslated region containing seven UG repeats. The binding activity of this protein cycles on a daily basis, decreasing at the beginning of the night when synthesis of luciferin-binding protein starts and increasing at the end of the night when synthesis of luciferin-binding protein stops. This suggests that it functions as a clock-controlled repressor, preventing the translation of lbp mRNA during the day. PMID- 8202479 TI - Angular orientation of the stable tyrosyl radical within photosystem II by high field 245-GHz electron paramagnetic resonance. AB - The 4 K 245-GHz/8.7-T electron paramagnetic resonance spectrum of the stable tyrosyl radical in photosystem II, known as TyrD., has been measured. Illumination at 200 K enhances the signal intensity of TyrD. by a factor of > 40 compared to the signal obtained from dark-adapted samples. This signal enhancement and the unusual line shape of the TyrD. resonance result from the magnetic dipolar coupling of the radical to the manganese cluster involved in oxygen evolution. The relative angular orientation of the manganese cluster with respect to TyrD. has been determined from line-shape analysis. The resonance arising from TyrD. in Tris-washed manganese-free photosystem II sample is also distorted. This effect probably originates from the influence of the nonheme iron on the spin relaxation of the tyrosyl radical. The relative angular orientation of the nonheme iron has also been determined. Oriented samples were used to determine the angular orientation of TyrD. with respect to the membrane plane. Combining angular data with published distances, we have constructed a three dimensional picture of the relative positions of TyrD., the manganese cluster, and the nonheme iron. The data suggest a more symmetrical placement of the manganese relative to TyrD. and TyrZ, the tyrosine involved in electron transfer, than is usually assumed in current models of photosystem II. PMID- 8202480 TI - Exo-endocytosis and closing of the fission pore during endocytosis in single pituitary nerve terminals internally perfused with high calcium concentrations. AB - An increase in free Ca2+ triggers exocytosis in pituitary nerve terminals leading to an increase in membrane area and membrane capacitance. When Ca2+ is increased by step depolarization, an instantaneous capacitance increase during the first 80 ms is followed by a slow increase extending over several seconds. We measured capacitance changes associated with exocytosis and endocytosis in single pituitary nerve terminals internally perfused with high Ca2+. At 50 microM Ca2+ the capacitance increased by up to 2%/s, similar to the slow phase observed during depolarization. Our results indicate that at the site of fusion very high Ca2+ is required. Following exocytosis, large downward capacitance steps were measured, reflecting endocytosis of large vacuoles. These events were not abrupt but reflected a gradual decrease of fission pore conductance from 8 nS to < 40 pS during 500 ms, revealing the dynamics of individual fission pore closures. Above 300 pS, narrowing of the endocytotic fission pore was approximately 10 times slower than the previously reported expansion of the exocytotic fusion pore. The transition between 300 pS and 0 pS took approximately 200 ms, whereas it has been reported that the exocytotic fusion pore measured in mast cells opens from 0 to 280 pS in < 100 microseconds. The time course of closing of the fission pore may be explained by an exponential decrease in pore diameter occurring at a constant rate. PMID- 8202481 TI - Linker DNA accessibility in chromatin fibers of different conformations: a reevaluation. AB - New studies on chromatin fiber morphology, using the technique of scanning force microscopy (SFM), have caused us to reexamine recent analysis of nuclease digestion of chromatin. Chicken erythrocyte chromatin fibers, glutaraldehyde fixed at 0, 10, and 80 mM NaCl, were imaged with the help of SFM. The chromatin fibers possessed a loose three-dimensional 30-nm structure even in the absence of added salt. This structure slightly condensed upon addition of 10 mM NaCl, and highly compacted, irregularly segmented fibers were observed at 80 mM NaCl. This sheds new light upon our previously reported analysis of the kinetics of digestion by soluble and membrane-immobilized micrococcal nuclease [Leuba, S. H., Zlatanova, J. & van Holde, K. (1994) J. Mol. Biol. 235, 871-880]. While the low ionic-strength fibers were readily digested, the highly compacted structure formed at 80 mM NaCl was refractory to nuclease attack, implying that the linkers were fully accessible in the low-ionic-strength conformation but not in the condensed fibers. We now find that cleavage of the linker DNA by a small molecule, methidiumpropyl-EDTA-Fe(II), proceeds for all types of conformations at similar rates. Thus, steric hindrance is responsible for the lack of accessibility to micrococcal nuclease in the condensed fiber. Taken in total the data suggest that reexamination of existing models of chromatin conformation is warranted. PMID- 8202482 TI - Epithelial differentiation of metanephric mesenchymal cells after stimulation with hepatocyte growth factor or embryonic spinal cord. AB - Mammalian kidney emerges from metanephric mesenchyme following the insertion of a migrating ureteric bud. The pattern morphology of mesenchymal specialization during tubular segmentation is remarkably complex, and the relative contribution of pattern gradients from the microenvironment versus the instructive role of individual cells is not known. We have started to examine the differentiation of metanephric mesenchyme using cultures of metanephric ridge (MMR) cells from day 13.5 mouse embryos to investigate the conversion of mesenchyme toward kidney epithelium in vitro. One of our mesenchymal clones, MMR1, expresses little Pax2, uvomorulin, or cytokeratin but does express neural cell adhesion molecule, bc12, and desmin; these are properties consistent with an early stem cell. Coculture of MMR1 cells with embryonic spinal cord leads to the induction of a more differentiated cell phenotype characterized by decreased expression of neural cell adhesion molecule, the appearance of uvomorulin, and the emergence of cytokeratin, all consistent with an evolution toward epithelium. We were also able to detect the hepatocyte growth factor receptor c-met on MMR1 cells by indirect immunofluorescence. When MMR1 cells were stimulated with hepatocyte growth factor, neural cell adhesion molecule expression decreased and uvomorulin appeared. This effect of hepatocyte growth factor, as a single cytokine, may be important in the early assemblage of kidney, since we were able to detect mRNA transcripts encoding c-met from mouse embryo metanephric kidneys. PMID- 8202483 TI - A cell cycle-regulated inhibitor of cyclin-dependent kinases. AB - Cyclin-dependent kinases (Cdks) previously have been shown to drive the major cell cycle transitions in eukaryotic organisms ranging from yeast to humans. We report here the identification of a 28-kDa protein, p28Ick (inhibitor of cyclin dependent kinase), that binds to and inhibits the kinase activity of preformed Cdk/cyclin complexes from human cells. p28 inhibitory activity fluctuates during the cell cycle with maximal levels in G1 and accumulates in G1- and G0-arrested cells. These results suggest that control of the G1/S transition may be influenced by a family of Cdk inhibitors that include p28Ick and the recently described inhibitors p21Cip1/Waf1/Cap20 and p16Ink4. PMID- 8202484 TI - Mouse stem cell antigen Sca-2 is a member of the Ly-6 family of cell surface proteins. AB - Mature T lymphocytes arise from intrathymic T-cell precursors, which in turn are derived from a multipotent stem cell in the bone marrow. Unlike bone marrow stem cells, the differentiation potential of the earliest intrathymic precursor cells is strongly biased toward the lymphoid lineage. The major difference in cell surface phenotype between early thymic precursor cells and bone marrow stem cells is that the former population expresses Sca-2. The progeny of the intrathymic precursor population continue to express Sca-2 until the transition from blast cells to small cells, at which stage expression of Sca-2 is down regulated. Mature thymocytes and peripheral T cells do not express detectable levels of Sca 2, whereas peripheral B cells are Sca-2-positive. We report herein the complete sequence of mouse Sca-2 deduced from a thymocyte cDNA clone. Sca-2 is a member of the Ly-6 family, a group of small cysteine-rich cell surface proteins that are anchored in the membrane by a glycosyl-phosphatidylinositol moiety. PMID- 8202485 TI - The LW blood group glycoprotein is homologous to intercellular adhesion molecules. AB - The LW blood group antigens reside on a 42-kDa erythrocyte membrane glycoprotein that was purified by immunoaffinity and partially sequenced. From this information, a specific PCR-amplified DNA fragment was used to screen a lambda gt11 human bone marrow cDNA library. Two forms of cDNA were isolated; the first encoded a single spanning transmembrane protein of 270 amino acids, including a 29-amino acid peptide signal and four potential N-glycosylation sites, and the second encoded a shortened protein form of 236 residues devoid of transmembrane and cytoplasm domains. A rabbit antibody raised against the 15 N-terminal amino acids of the predicted protein reacted on immunoblots with authentic LW glycoprotein and in indirect agglutination test with all human erythrocytes except those from LW(a-b-). This showed that the protein encoded by these clones was LW gene product and suggested that the N terminus of the LW protein is oriented extracellularly. Most interestingly, the LW protein was found to exhibit sequence similarities (with approximately 30% identity) with intercellular adhesion molecules ICAM-1, -2, and -3, which are the counter-receptors for the lymphocyte function-associated antigens LFA-1. The extracellular domain of LW consists, like that of ICAM-2, of two immunoglobulin-like domains, and the critical residues involved in the binding of LFA-1 to ICAMs were partially conserved in LW. PMID- 8202486 TI - Fast photoinduced electron transfer through DNA intercalation. AB - We report evidence for fast photoinduced electron transfer mediated by the DNA helix that requires metal complexes that are avid intercalators of DNA. Here the donor bis(phenanthroline)(dipyridophenazine)ruthenium(II) [Ru(phen)2dppz2+] and acceptor bis(9,10-phenanthrenequinone diimine)(phenanthroline)rhodium(III) [Rh(phi)2phen3+] intercalate into DNA with Kb > 10(6) M-1. Luminescence quenching experiments in the presence of two different lengths of DNA yield upward-curving Stern-Volmer plots and the loss of luminescence intensity far exceeds the change in emission lifetimes. In the presence of a nonintercalative electron acceptor, Ru(NH3)3+(6), Ru(phen)2dppz2+ luminescence is quenched much less efficiently compared to that found for the intercalative Rh(phi)2phen3+ quencher and follows linear Stern-Volmer kinetics; steady-state and time-resolved Stern-Volmer plots are comparable in scale. These experiments are consistent with a model involving fast long-range electron transfer between intercalators through the DNA helix. PMID- 8202487 TI - p53-dependent G1 arrest involves pRB-related proteins and is disrupted by the human papillomavirus 16 E7 oncoprotein. AB - The cell cycle regulatory tumor suppressor proteins p53 and pRB are targeted for inactivation by several tumor viruses, including the high-risk types of human papillomaviruses (HPVs) via interactions of the HPV E6 and E7 oncoproteins with p53 and pRB, respectively. p53 plays a central role in a signal transduction pathway that mediates G1 arrest after DNA damage, though the mechanism by which G1 arrest occurs has not been elucidated. The cyclin-associated protein p21waf1/cip1 has recently been shown to be induced by p53 and to inhibit cyclin complex-mediated phosphorylation of pRB in vitro. Thus, we investigated a possible role for pRB in the p53-mediated DNA damage response. After gamma irradiation, cells expressing wild-type p53 arrested in G1, contained increased levels of WAF1/CIP1 mRNA, and demonstrated accumulation of hypophosphorylated pRB. In contrast, cell lines with abnormal p53 genes or with p53 functionally inactivated by the E6 oncoprotein of HPV16 (a high-risk HPV) failed to arrest in G1, did not elevate WAF1/CIP1 mRNA, and did not accumulate hypophosphorylated pRB. Despite apparently normal elevation of p53 protein and WAF1/CIP1 mRNA after irradiation, cells expressing HPV16 E7 also failed to arrest in G1 and did not accumulate hypophosphorylated pRB. Disruption of RB genes alone did not totally abrogate this G1 arrest. Our results suggest that p53 indirectly regulates phosphorylation of pRB and that pRB and/or other pRB-like molecules that bind to HPV16 E7 participate in the DNA damage-mediated G1 arrest signal. In the process of HPV infection, the HPV E6 and E7 oncoproteins may undermine this cell cycle checkpoint, contributing to the accumulation of genetic alterations during tumorigenesis. PMID- 8202488 TI - BST-1, a surface molecule of bone marrow stromal cell lines that facilitates pre B-cell growth. AB - Bone marrow stromal cells are essential for B-lymphocyte development. However, how stromal cells regulate B lymphopoiesis is not clear. In this paper, we report the molecular cloning of a stromal cell line-derived glycosyl phosphatidylinositol-anchored molecule, BST-1, that facilitates pre-B-cell growth. The deduced amino acid sequence of BST-1 exhibited 33% identity with CD38. BST-1 was expressed in a wide range of tissues and in umbilical vein endothelial cells, whereas it was scarcely expressed in a variety of hematopoietic cell lines. The gene for BST-1 was assigned to chromosome 14q32.3, where immunoglobulin heavy-chain genes are clustered. BST-1 expression was enhanced in rheumatoid arthritis patient-derived bone marrow stromal cell lines that were previously shown to have an enhanced ability to support the growth of a pre-B-cell line as compared with stromal cell lines derived from healthy donors. PMID- 8202489 TI - Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP. AB - Recent clinicopathologic studies have shown that many prostatic adenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growth-regulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgen-independent line PC-3-M, elevation of cAMP through addition of cAMP analogues or phosphodiesterase inhibitors induced a markedly neuronal morphology. Also in LNCaP cells ultrastructural analysis showed that cAMP induced the appearance of neurosecretory cell-like dense-core granules. Phenotypic analysis of untreated LNCaP and PC-3-M cells showed that both cell lines express markers of the neural crest including S-100, chromogranin A, pp60c src, and neuron-specific enolase as well as the epithelial marker KS1/4 and stage specific embryonic antigen 4. In PC-3-M cells, cAMP markedly elevated neuron specific enolase protein and caused an increase in the specific activity of the neuroendocrine marker pp60c-src, and in both cell lines expression of KS1/4 and stage-specific embryonic antigen 4 was down-regulated. In addition to effects on lineage markers, cAMP treatment induced G1 synchronization, growth arrest, and loss of clonogenicity, indicating terminal differentiation. Our data provide direct evidence of plasticity in the lineage commitment of adenocarcinoma of the prostate. We have shown that cell-permeant cAMP analogues can induce terminal differentiation, suggesting that hydrolysis-resistant cyclic nucleotides may present an additional approach to the treatment of advanced prostate cancer. PMID- 8202490 TI - Role of Src homology 3 domains in assembly and activation of the phagocyte NADPH oxidase. AB - The phagocyte NADPH oxidase, dormant in resting cells, is activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. The activated oxidase is a complex of membrane-integrated cytochrome b558, composed of 91-kDa (gp91phox) and 22-kDa (p22phox) subunits, and two cytosolic factors (p47phox and p67phox), each containing two Src homology 3 (SH3) domains. Here we show that the region of the tandem SH3 domains of p47phox (p47-SH3) expressed as a glutathione S-transferase fusion protein inhibits the superoxide production in a cell-free system, indicating involvement of the domains in the activation. Furthermore, we find that arachidonic acid and sodium dodecyl sulfate, activators of the oxidase in vitro, cause exposure of p47-SH3, which has probably been masked by the C-terminal region of this protein in a resting state. The unmasking of p47-SH3 appears to play a crucial role in the assembly of the oxidase components, because p47-SH3 binds to both p22phox and p67phox but fails to interact with a mutant p22phox carrying a Pro-156-->Gln substitution in a proline rich region, which has been found in a patient with chronic granulomatous disease. Based on the observations, we propose a signal-transducing mechanism whereby normally inaccessible SH3 domains become exposed upon activation to interact with their target proteins. PMID- 8202492 TI - Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. AB - Four inherited neurodegenerative diseases are linked to abnormally expanded repeats of glutamine residues in the affected proteins. Molecular modeling followed by optical, electron, and x-ray diffraction studies of a synthetic poly(L-glutamine) shows that it forms beta-sheets strongly held together by hydrogen bonds. Glutamine repeats may function as polar zippers, for example, by joining specific transcription factors bound to separate DNA segments. Their extension may cause disease either by increased, nonspecific affinity between such factors or by gradual precipitation of the affected proteins in neurons. PMID- 8202491 TI - Disulfide cross-linking in crude embryonic lysates reveals three complexes of the Drosophila morphogen dorsal and its inhibitor cactus. AB - In Drosophila embryos dorsoventral polarity is determined by a concentration gradient of dorsal (dl) protein in the nuclei formed by the differential regulation of nuclear localization of dl protein. cactus (cact) represses the nuclear localization of dl protein. By introducing intermolecular disulfide bonds in homogenates of embryos, we detected three complexes of dl and/or cact proteins. Complex 1 (190 kDa) is a dl protein homodimer (dl2). Complex 2 (270 kDa) consists of one complex 1 and one cact molecule (dl2cact). Complex 3 (200 kDa) is a cact protein complex that does not contain dl protein. In wild-type embryos dl2cact was detected as the major form of dl protein, and dl2 was minor. With this assay virtually no dl monomer is detected. Analysis of the dl protein complexes in ventralized and dorsalized mutant embryos indicates that dl2cact is a cytoplasmic form, whereas dl2 is localized mainly in the nuclei. It seems that a small amount of dl2 is also present in the cytoplasm. PMID- 8202493 TI - Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice. AB - S100 beta is a calcium-binding protein that is expressed at high levels in brain primarily by astrocytes. Addition of the disulfide-bonded dimeric form of S100 beta to primary neuronal and glial cultures and established cell lines induces axonal extension and alterations in astrocyte proliferation and phenotype, but evidence that S100 beta exerts the same effects in vivo has not been presented. An 8.9-kb murine S100b genomic clone was used to produce two lines of transgenic mice in which S100 beta RNA is increased in a dose-related manner to 2-fold and 7 fold above normal. These lines show concomitant increased S100 beta protein throughout the brain. Expression in both lines is cell type- and tissue appropriate, and expression levels are correlated with the transgene copy number, demonstrating that sequences necessary for normal regulation of the gene are included within the cloned segment. In the hippocampus of adult transgenic mice, Western blotting detects elevated levels of glial fibrillary acidic protein and several markers of axonal sprouting, including neurofilament L, phosphorylated epitopes of neurofilament H and M, and beta-tubulin. Immunocytochemistry demonstrates alterations in astrocyte morphology and axonal sprouting, especially in the dentate gyrus. Thus, both astrocytosis and neurite proliferation occur in transgenic mice expressing elevated levels of S100 beta. These transgenic mice provide a useful model for studies of the role of S100 beta in glial-neuronal interactions in normal development and function of the brain and for analyzing the significance of elevated levels of S100 beta in Down syndrome and Alzheimer disease. PMID- 8202494 TI - Island rescue PCR: a rapid and efficient method for isolating transcribed sequences from yeast artificial chromosomes and cosmids. AB - The identification of transcripts from large genomic regions cloned in yeast artificial chromosomes (YACs) or cosmids continues to be a critical and often rate-limiting step in positional cloning of human disease genes. We have developed a PCR-based method for rapid and efficient generation of probes from YACs or cosmids that can be used for cDNA library screening. The method, which we call island rescue PCR (IRP), is based upon the observation that the 5' ends of many genes are associated with (G+C)-rich regions called CpG islands. In IRP, the YAC of interest is digested with a restriction enzyme that recognizes sequences of high CpG content, and vectorette linkers are ligated to the cleaved ends. The PCR is used to amplify the region extending from the cleaved restriction enzyme site to the nearest SINE (Alu) repeat. In many cases this product contains sequences from the 5' end of the associated gene. cDNA clones isolated with these products are then verified by mapping them back to the original YAC. The method allows rapid screening of > 500 kb of human genomic insert in one experiment, is tolerant of contaminating yeast sequences, and can also be applied to cosmid pools. In a control experiment, the method was able to identify cDNA clones for the neurofibromatosis type 1 (NF1) gene using a probe generated from a YAC in the region. Application of IRP has yielded nine other genes from YACs isolated from chromosome locations 4p16.3 and 17q21. PMID- 8202495 TI - Pregnancy-related steroids are potential negative regulators of B lymphopoiesis. AB - B lymphopoiesis is selectively suppressed in normal pregnant mice, suggesting that fluctuations in systemic hormone levels might influence local events within bone marrow. This has now been tested by sustained experimental elevation of sex steroids by hormone-containing pellet implants. We found that while numbers of total nucleated cells declined after treatment with estrone, beta-estradiol, or estriol, there was preferential suppression of B-lymphocyte lineage precursors. Progesterone pellets had no effect when used alone, but mice exposed to progesterone were sensitive to several-logarithm lower concentrations of estrogen. Changes in subpopulations of B-lymphocyte lineage cells with hormone pellets were similar to those previously recorded in pregnancy. B-lymphocyte lineage precursors in male and female mice were sensitive to these sex hormones. Acute treatment with single injections of water-soluble beta-estradiol allowed temporal effects on B-lineage cells to be documented. With this protocol, total numbers of nucleated cells and myeloid progenitor cells remained unchanged. Interleukin 7-responsive precursors dramatically declined within 1 day of injection, suggesting that estrogen influences that stage in the B-lymphocyte lineage. There was a subsequent sharp drop in small pre-B cells 4 days after this transient elevation in estrogen. These experiments demonstrate that B lymphopoiesis is sensitive to negative regulation by sex steroids. They extend findings made with pregnant animals and parallel previous studies of the thymus. Sex steroids might contribute to control of steady-state lymphopoiesis, and fluctuations in their levels could have implications for human disease. PMID- 8202496 TI - Insulin promotes the biosynthesis and secretion of apolipoprotein B-48 by altering apolipoprotein B mRNA editing. AB - Long-term insulin treatment selectively stimulates secretion of the truncated form of apolipoprotein B (apoB), apoB-48, from primary rat hepatocytes in culture. Chronic treatment with insulin at 400 ng/ml causes a 3-fold increase in total apoB secretion, with apoB-48 making up about 75% of that increase. apo-B-48 is the protein product generated by translation of full-length apoB mRNA which has been modified by a posttranscriptional editing mechanism. Editing changes codon 2153 in the middle of the apoB-100 coding region from CAA, coding for glutamine, to UAA, a translation stop signal. We therefore examined the effect of insulin treatment on the ratio of edited to nonedited apoB mRNA in RNA isolated from primary rat hepatocyte cultures. There was a dramatic shift in the ratio of edited versus nonedited forms of apoB mRNA, from about 1:1 in untreated cells to 7:1 in insulin-treated cells. Insulin exerted a dose-dependent effect on apoB secretion and apoB mRNA editing over the range of insulin concentrations studied (0.4-400 ng/ml). In contrast, oleic acid, which also increased apoB (B-48 and B 100) secretion, had no significant effect on the ratio of apoB-48 to apoB-100 particles secreted and no effect on the proportion of edited apoB mRNA. Neither insulin nor oleic acid affects total apoB mRNA levels as assayed by Northern blot analysis. These data strongly suggest that insulin stimulates biosynthesis and secretion of apoB-48 in rat hepatocytes by regulating the proportion of edited apoB mRNA. PMID- 8202498 TI - Mapping of herpes simplex virus 1 genes with mutations which overcome host restrictions to infection. AB - Earlier studies have shown that the thymidine kinase-negative baby hamster kidney (BHKTK-) cell lines expressing constitutively the herpes simplex virus 1 (HSV-1) glycoprotein D (gD), designated BJ, restrict infection by HSV-1 at the level of virus entry. U10, a HSV-1 mutant not restricted by the BJ cells, carried the substitution of proline for Leu25 in the gD gene, suggesting that gD encodes a specialized domain which precludes virus entry into cells expressing gD. Analyses of a new series of 36 unrestricted viral mutants showed the following. (i) Only two mutants contained mutations at a site which did not overlap with the previously reported mutation. A representative of a previously mapped mutant and one of the two new mutants were examined in detail. Thus, in the gD of mutant U30 Ala185 was replaced by threonine, whereas in gD of U21, Ala185 and Leu25 were replaced with threonine and proline, respectively. U30 and U21 multiplied better than the wild-type parent virus in the parental BHKTK- cells. (ii) Transfer of the gD gene from U21 or U30 to wild-type parent virus or to the gD- virus FgD beta yielded recombinants which, while capable of infecting BJ cells, were considerably less efficient than the parent unrestricted mutants, suggesting that the latter contained additional mutations which were responsible in part for the unrestricted phenotype. Conversely, marker rescue of mutant viruses with wild type gD reduced but did not abrogate entirely the unrestricted phenotype. (iii) Mutations in gD which conferred the unrestricted phenotype were not random. (iv) gD plays a role in the restriction, inasmuch as preincubation of cells expressing gD with antibodies to gD abolished restriction. (v) In mutant R5000, the gD substitution Ser140 to Asn was capable of overcoming a restriction of a BHKTK- clonal line which does not express gD but conferred very low ability to replicate on BJ cells. We conclude that (a) uncloned stocks of BHKTK- cells exhibit a low level restriction to infection with wild-type virus, (b) clonal lines of BHKTK- cells which vary with respect to the stringency of restriction express either allelic genes differing in the properties of their products or products of different genes, and (c) both the restricted and unrestricted phenotypes reflect the interactions of gD with these cellular products. The implications of these conclusions with respect to the restriction imposed on BHK cells by the expression of gD are discussed. PMID- 8202497 TI - Induction of cytochrome CYPIA1 and formation of toxic metabolites of benzo[a]pyrene by rat aorta: a possible role in atherogenesis. AB - Cigarette smoking is a leading risk factor for atherosclerosis. Endothelial injury may be the initial event in this process. The carcinogenic metabolites of the polycyclic aromatic hydrocarbons found in cigarette smoke tars could cause this injury. We tested this model by examining the effect of 3-methylcholanthrene administration on aortic polycyclic aromatic hydrocarbon metabolism. Immunoblotting with a monoclonal antibody (mAb 1-7-1) specific for cytochromes CYPIA1 and CYPIA2 showed that aortic microsomes from treated, but not from control, animals contained CYPIA1; the CYPIA1 was primarily in the endothelium. Aortic microsomes from induced animals metabolized benzo[a]pyrene (BaP) to the 7R,8S,9,10-tetrahydrotetrol-, 7,8-dihydrodiol-, 1,6 quinone-, 3,6 quinone-, 6,12 quinone-, 3-hydroxy-, and 9-hydroxy-BaP. mAb 1-7-1 inhibited the formation of the tetrahydrotetrol, the dihydrodiol-BaP, and the 3-hydroxy-BaP but did not inhibit the quinones or the 9-hydroxy-BaP. Arachidonic acid did not affect metabolism. These data suggest that the aortas of induced animals metabolize the BaP in cigarette smoke to carcinogenic and toxic products and that this metabolism may initiate vessel injury and lead to the accelerated atherosclerosis seen in cigarette smokers. PMID- 8202499 TI - Opsins with mutations at the site of chromophore attachment constitutively activate transducin but are not phosphorylated by rhodopsin kinase. AB - More than 70 mutations in the gene encoding the visual pigment rhodopsin have been identified in patients with autosomal dominant retinitis pigmentosa. Most of these mutations are thought to interfere with proper folding of the membrane protein. However, families with a severe phenotype of retinitis pigmentosa have been identified and shown to carry a mutation at the site of chromophore attachment, Lys-296. This mutation disrupts the inactive conformation of opsin and results in a constitutively active protein that can activate the rod-specific GTP-binding protein, transducin, in the absence of light and in the absence of the chromophore 11-cis-retinal. It has been suggested that this mutant opsin molecule may cause rod degeneration by depletion of the components used to inactivate rhodopsin, such as rhodopsin kinase. In this work we test this idea by determining whether two constitutively active opsin mutants are phosphorylated by rhodopsin kinase. We found that opsin mutants where Lys-296 is replaced either by Glu (K296E) or by Gly (K296G) are not substrates of rhodopsin kinase in the absence of chromophore. However, when K296G is regenerated with a Schiff base complex of 11-cis-retinal and n-propylamine and exposed to illumination, phosphorylation of opsin occurs. These experiments suggest that in the rod photoreceptors of patients with retinitis pigmentosa carrying a mutation at Lys 296, there is persistent activation of the GTP-binding protein-mediated cascade. This may result in a situation that mimics long-term exposure to continuous illumination and results in the degeneration of photoreceptors. PMID- 8202500 TI - Activation of the pp90rsk and mitogen-activated serine/threonine protein kinases by ionizing radiation. AB - The cellular response to ionizing radiation (IR) includes induction of the c-jun and EGR1 early response genes. The present work has examined potential cytoplasmic signaling cascades that transduce IR-induced signals to the nucleus. The results demonstrate activation of the 40S ribosomal protein S6 kinase, pp90rsk, in human U-937 myeloid leukemia cells. Partial purification of pp90rsk by affinity chromatography demonstrated an increase in S6 peptide phosphorylation when comparing irradiated with control cells. IR-induced activation of pp90rsk was further confirmed in immune-complex kinase assays. In contrast to these findings, there was no detectable induction of pp70S6K. Previous work has demonstrated that mitogen-activated protein kinase activates pp90rsk. The present results further show that IR treatment is associated with induction of mitogen activated protein kinase activity and that this event is temporally related to activation of pp90rsk and early response gene expression. These findings suggest that activation of the mitogen-activated protein kinase/pp90rsk cascade is involved in the response of cells to IR exposure. PMID- 8202501 TI - Properties of permease dimer, a fusion protein containing two lactose permease molecules from Escherichia coli. AB - An engineered fusion protein containing two tandem lactose permease molecules (permease dimer) exhibits high transport activity and is used to test the phenomenon of negative dominance. Introduction of the mutation Glu-325-->Cys into either the first or the second half of the dimer results in a 50% decrease in activity, whereas introduction of the mutation into both halves of the dimer abolishes transport. Lactose transport by permease dimer is completely inactivated by N-ethylmaleimide; however, 40-45% activity is retained after N ethylmaleimide treatment when either the first or the second half of the dimer is replaced with a mutant devoid of cysteine residues. The observations demonstrate that both halves of the fusion protein are equally active and suggest that each half may function independently. To test the possibility that oligomerization between dimers might account for the findings, a permease dimer was constructed that contains two different deletion mutants that complement functionally when expressed as untethered molecules. Because this construct does not catalyze lactose transport to any extent whatsoever, it is unlikely that the two halves of the dimer interact or that there is an oligomeric interaction between dimers. The approach is consistent with the contention that the functional unit of lactose permease is a monomer. PMID- 8202502 TI - Luminescent oxygen channeling immunoassay: measurement of particle binding kinetics by chemiluminescence. AB - A method for monitoring formation of latex particle pairs by chemiluminescence is described. Molecular oxygen is excited by a photosensitizer and an antenna dye that are dissolved in one of the particles. 1 delta gO2 diffuses to the second particle and initiates a high quantum yield chemiluminescent reaction of an olefin that is dissolved in it. The efficiency of 1 delta gO2 transfer between particles is approximately 3.5%. The technique permits real-time measurement of particle binding kinetics. Second-order rate constants increase with the number of receptor binding sites on the particles and approach diffusion control. By using antibody-coated particles, a homogeneous immunoassay capable of detecting approximately 4 amol of thyroid-stimulating hormone in 12 min was demonstrated. Single molecules of analyte produce particle heterodimers that are detected even when no larger aggregates are formed. PMID- 8202503 TI - The cytoplasmic domain of the Na+/H+ exchangers (NHEs) dictates the nature of the hormonal response: behavior of a chimeric human NHE1/trout beta NHE antiporter. AB - Studies of the effect of cAMP on the cloned Na+/H+ exchangers (NHEs) are difficult to interpret as variable results have been reported for the different isoforms when expressed in various cell types. We took advantage of the fact that the human NHE1 and the trout erythrocyte beta NHE, when expressed in the same cell line, PS120, respond differently to cAMP (NHE1 is insensitive, beta NHE is activated) to analyze the molecular mechanisms of cAMP activation. We constructed both a chimera between NHE1 and beta NHE and a set of beta NHE mutants to delineate the critical parts of the molecule involved in the activation process. NHE1 becomes cAMP stimulated when its cytoplasmic domain is replaced by the cytoplasmic domain of beta NHE; thus, the cytoplasmic C terminus of beta NHE, which contains two cAMP-dependent consensus sequences, is essential to confer cAMP dependence. Serine to glycine substitution of only one of the two protein kinase A (PKA) consensus sites decreased by 60% the ability of cAMP to activate Na+/H+ exchange. Simultaneous Ser to Gly substitution of the two PKA consensus sites decreased the cAMP-mediated activation by 72%. The residual activation required a cytoplasmic fragment (aa 559-661) that contains four sequences considered likely as putative PKA consensus sites. The results obtained with the chimeric NHE also demonstrated that if the cytoplasmic C terminus is crucially involved in the hormonal activation, the rate of Na+/H+ exchange so induced can be modulated by the nature of the interaction between the N- and C-terminal domains. PMID- 8202504 TI - Limb and lower-body duplications induced by retinoic acid in mice. AB - The zygote and subsequent preimplantation stages of early mammalian development are susceptible to certain chemical perturbations that cause abnormal development of the conceptus. In certain cases, disruption in patterns of gene expression could be a primary event leading to abnormal development. To investigate this hypothesis, we treated pregnant mice with trans-retinoic acid, a known modulator of gene expression. Treatments were administered at various times during pregastrulation stages and the presumed onset of gastrulation. trans-Retinoic acid induced a distinctive set of malformations, as manifest by supernumerary and ectopic limbs and duplication of portions of the lower body, but only when administered during the period of 4.5-5.5 days after mating. (Other malformations were induced at different stages.) The limb and lower-body duplications suggest that exogenous trans-retinoic acid may influence not only the pattern for the hindlimbs but also that for the entire lower body. Since it appears likely that the embryos were affected in the late blastocyst and proamniotic-embryo stages, the provocative possibility arises that aspects of pattern formation of limbs and lower body actually occur prior to gastrulation. PMID- 8202505 TI - Methane production in terrestrial arthropods. AB - We have screened more than 110 representatives of the different taxa of terrestrial arthropods for methane production in order to obtain additional information about the origins of biogenic methane. Methanogenic bacteria occur in the hindguts of nearly all tropical representatives of millipedes (Diplopoda), cockroaches (Blattaria), termites (Isoptera), and scarab beetles (Scarabaeidae), while such methanogens are absent from 66 other arthropod species investigated. Three types of symbiosis were found: in the first type, the arthropod's hindgut is colonized by free methanogenic bacteria; in the second type, methanogens are closely associated with chitinous structures formed by the host's hindgut; the third type is mediated by intestinal anaerobic protists with intracellular methanogens. Such symbiotic associations are likely to be a characteristic property of the particular taxon. Since these taxa represent many families with thousands of species, the world populations of methane-producing arthropods constitute an enormous biomass. We show that arthropod symbionts can contribute substantially to atmospheric methane. PMID- 8202506 TI - A role for destabilizing amino acid replacements in light-chain amyloidosis. AB - Light-chain (L-chain) amyloidosis is characterized by deposition of fibrillar aggregates composed of the N-terminal L-chain variable region (VL) domain of an immunoglobulin, generally in individuals overproducing a monoclonal L chain. In addition to proteolytic fragmentation and high protein concentration, particular amino acid substitutions may also contribute to the tendency of an L chain to aggregate in L-chain amyloidosis, although evidence in support of this has been limited and difficult to interpret. In this paper we identify particular amino acid replacements at specific positions in the VL domain that are occupied at frequencies significantly higher in those L chains associated with amyloidosis. Analysis of the structural model for the VL domain of the Bence-Jones protein REI suggests that these positions play important roles in maintaining domain structure and stability. Using an Escherichia coli expression system, we prepared single-point mutants of REI VL incorporating amyloid-associated amino acid replacements that are both rare and located at structurally important positions. These mutants support ordered aggregate formation in an in vitro L-chain fibril formation model in which wild-type REI VL remains soluble. Moreover, the ability of these sequences to aggregate in vitro correlates well with the extent to which domain stability is decreased in denaturant-induced unfolding. The results are consistent with a mechanism for the disease process in which the VL domain, either before or after proteolytic cleavage from the L-chain constant region domain, unfolds by virtue of one or more destabilizing amino acid replacements to generate an aggregation-prone nonnative state. PMID- 8202507 TI - Cell fates in leech embryos with duplicated lineages. AB - We have examined the fates of the progeny of supernumerary embryonic stem cells (O/P teloblasts) generated by microinjecting polyadenylic acid into newborn O/P teloblasts in embryos of the leech, Helobdella triserialis. In normal development, each O/P teloblast generates a rostrocaudal column of daughter cells (primary blast cells) that contribute distinct segmentally iterated O or P sets of epidermal and neural progeny to the mature leech. Previous results suggest that primary blast cells derived from ipsilateral pairs of O/P teloblasts are equipotent and equivalent at birth; that they and their progeny assume distinct O or P fates according to hierarchical and position-dependent interactions; and that the P fate is the primary, or default, fate and the O fate is the secondary fate. In the work presented here, one O/P teloblast was experimentally induced to undergo a supernumerary equal division, and the developmental fates of the progeny of the three (two "duplicate" and one "nonduplicate") ipsilateral O/P teloblasts were determined at stages 8 and 10. We find that some supernumerary O/P teloblasts produce supernumerary P progeny, whereas others generate supernumerary O progeny. When three O/P-derived bandlets are present, bandlets derived from the duplicate O/P teloblasts give rise to progeny of the same (O or P) fate. When the nonduplicate bandlet is absent, the duplicate bandlets assume distinct O and P fates. These results suggest that ipsilateral sister O/P teloblasts, while equipotent, might not be equivalent. PMID- 8202508 TI - A net +1 frameshift permits synthesis of thymidine kinase from a drug-resistant herpes simplex virus mutant. AB - Clinical resistance to antiviral drugs requires that a virus evade drug therapy yet retain pathogenicity. Thymidine kinase (TK)-negative mutants of herpes simplex virus are resistant to the drug, acyclovir, but are attenuated for pathogenicity in animal models. However, numerous cases of clinical resistance to acyclovir have been associated with viruses that were reported to express no TK activity. We studied an acyclovir-resistant clinical mutant that contains a single-base insertion in its tk gene, predicting the synthesis of a truncated TK polypeptide with no TK activity. Nevertheless, the mutant retained some TK activity and the ability to reactivate from latent infections of mouse trigeminal ganglia. The mutant expressed both the predicted truncated polypeptide and a low level of a polypeptide that comigrated with full-length TK on polyacrylamide gels and reacted with anti-TK antiserum, providing evidence for a frameshifting mechanism. In vitro transcription and translation of mutant tk genes, including constructs in which reporter epitopes could be expressed only if frameshifting occurred, also gave rise to truncated and full-length polypeptides. Reverse transcriptase-polymerase chain reaction analysis coupled with open reading frame cloning failed to detect alterations in tk transcripts that could account for the synthesis of full-length polypeptide. Thus, synthesis of full-length TK was due to an unusual net +1 frameshift during translation, a phenomenon hitherto confined in eukaryotic cells to certain RNA viruses and retrotransposons. Utilization of cellular frameshifting mechanisms may permit an otherwise TK negative virus to exhibit clinical acyclovir resistance. PMID- 8202509 TI - Extraordinarily polymorphic microsatellite DNA in barley: species diversity, chromosomal locations, and population dynamics. AB - This study was undertaken to assess the extent of genetic variation in barley simple sequence repeats (SSRs) and to study the evolutionary dynamics of SSR alleles. SSR polymorphisms were resolved by the polymerase chain reaction with four pairs of primers. In total, 71 variants were observed in a sample of 207 accessions of wild and cultivated barley. Analyses of wheat-barley addition lines and barley doubled haploids identified these variants (alleles) with four loci, each located on a different chromosome. The numbers of alleles detected at a locus corresponded to the number of nucleotide repeats in the microsatellite sequences. The numbers of alleles at two loci were 28 and 37; to our knowledge these are the largest numbers of alleles for single Mendelian loci reported in plants. Three alleles were resolved by each of the other two loci. Allelic diversity was greater in wild than in cultivated barley and surveys of two generations (F8 and F53) of Composite Cross II, an experimental population of cultivated barley, showed that few of the alleles present in the 28 parents survived into generation F53, whereas some infrequent alleles reached high frequencies. Such changes in frequency indicate that the chromosomal segments marked by the SSR alleles are under the influence of natural selection. The SSR variants allow specific DNA sequences to be followed through generations. Thus, the great resolving power of SSR assays may provide clues regarding the precise targets of natural and man-directed selection. PMID- 8202510 TI - Spectrophotometric assay for enzyme-mediated unwinding of double-stranded DNA. AB - A method is described for monitoring the enzyme-mediated unwinding of duplex DNA spectrophotometrically. The assay employs a partially duplex oligonucleotide substrate modified at the complementary end with coumarin and fluorescein moieties. When in close proximity the fluorescein quenches the fluorescence of coumarin. However, when the strands are separated by the action of a DNA helicase, the coumarin fluorescence increases greatly. Therefore, the progress of enzyme-mediated DNA unwinding can be measured in real time by fluorescence spectroscopy. This assay provides a simple method to screen for helicase inhibitors, which are of growing interest as potential anticancer agents. The application of this technique to kinetic analyses of the mechanism of action of DNA helicases is also discussed. PMID- 8202511 TI - The bat gene of Halobacterium halobium encodes a trans-acting oxygen inducibility factor. AB - Oxygen and light affect the expression of the bacterioopsin gene (bop), which encodes a light-driven proton pump in the purple membrane of Halobacterium halobium. This response is thought to be mediated by a set of genes located adjacent to the bop gene. DNA fragments containing either the bop gene or the entire bop gene cluster reversed the phenotype of purple membrane-deficient strains with mutations in the bop gene. Purple membrane synthesis was constitutive in one of these strains transformed with the bop gene alone. The same strain transformed with the bop gene cluster was inducible by low oxygen tension. Moreover, another strain that constitutively expresses purple membrane remained constitutive when transformed with the bop gene alone but the phenotype of the strain changed to inducible when transformed with the bop gene cluster. Additional experiments have confirmed that one of the genes of the bop gene cluster, the bat gene, encodes a trans-acting factor that is necessary and sufficient to confer inducibility of purple membrane synthesis by low oxygen tension. PMID- 8202512 TI - Evidence that inactive p42 mitogen-activated protein kinase and inactive Rsk exist as a heterodimer in vivo. AB - Mitogen-activated protein kinases (MAP kinases) are active only when phosphorylated. Here we examine whether the activation of Xenopus p42 MAP kinase might involve changes in its association with other proteins as well as changes in its phosphorylation state. We find that when p42 MAP kinase is phosphorylated and active, it is monomeric, and that when p42 MAP kinase is nonphosphorylated and inactive, about half of it is monomeric and half is a component of a 110-kDa complex. We identify Rsk, an 82-kDa protein kinase that can be phosphorylated and partially activated by p42 MAP kinase, as being specifically associated with inactive p42 MAP kinase. It is possible that the complex of inactive p42 MAP kinase and inactive Rsk acts as a single signal reception particle and that the activation of the two kinases may be better described as a fork in a bifurcating signal transduction pathway than as successive levels in a kinase cascade. PMID- 8202513 TI - Liberation of an interaction domain from the phosphotransfer region of CheA, a signaling kinase of Escherichia coli. AB - The CheA protein of Escherichia coli is a histidine autokinase that donates its phosphate groups to two target proteins, CheY and CheB, to regulate flagellar rotation and sensory adaptation during chemotactic responses. The amino-terminal third of CheA contains the autophosphorylation site, determinants needed to interact with the catalytic center of the molecule, and determinants needed for specific recognition of its phosphorylation targets. To understand the structural basis for these activities, we examined the domain organization of the CheA phosphotransfer region by using DNA sequence analysis, limited proteolytic digestion, and a genetic technique called domain liberation. Comparison of the functionally interchangeable CheA proteins of E. coli and Salmonella typhimurium revealed two extensively mismatched segments within the phosphotransfer region, 22 and 25 aa long, with sequences characteristic of domain linkers. Both segments were readily susceptible to proteases, implying that they have an extended, flexible structure. In contrast, the intervening segments of the phosphotransfer region, designated P1 and P2 (roughly 140 and 65 aa, respectively), were relatively insensitive, suggesting they correspond to more compactly folded structural domains. Their functional properties were explored by identifying portions of the cheA coding region capable of interfering with chemotactic behavior when "liberated" and expressed as polypeptides. P1 fragments were not inhibitory, but P2 fragments blocked the interaction of CheY with the rotational switch at the flagellar motor, leading to incessant forward swimming. These results suggest that P2 contains CheY-binding determinants which are normally responsible for phosphotransfer specificity. Domain-liberation approaches should prove generally useful for analyzing multidomain proteins and their interaction targets. PMID- 8202514 TI - Structure and cell cycle-regulated transcription of the human cyclin A gene. AB - Cyclin A is a cell cycle regulatory protein that functions in mitotic and S-phase control in mammalian somatic cells. Its deregulated expression may have a role in cellular transformation. We have cloned and sequenced the human cyclin A gene and cDNAs representing its mRNAs and have characterized its promoter. Using synchronized cultures of NIH 3T3 cells stably transfected with cyclin A promoter/luciferase constructs, we show that the promoter is repressed during the G1 phase of the cell cycle and is activated at S-phase entry. Cell cycle regulation of the cyclin A gene promoter is mediated by sequences extending from 79 to +100 relative to the predominant transcription start site. It does not require the presence of a functional retinoblastoma protein. PMID- 8202515 TI - Female brain size and parental care in carnivores. AB - Comparative studies indicate that species differences in mammalian brain size relate to body size, ecology, and life-history traits. Previous analyses failed to show intrasexual or behavioral patterns of brain size in mammals. Across the terrestrial Carnivora, I find to the contrary. Differences in female, but not male, brain size associate with a fundamental ecological and evolutionary characteristic of female behavior. Other factors equal, females that provide the sole parental care have larger brains than those of biparental or communal species. For females, more parental investment accompanies larger brains. Future comparative studies of mammalian brain size must recognize that some patterns arise independently in the two sexes. PMID- 8202516 TI - Senescence of immortal human fibroblasts by the introduction of normal human chromosome 6. AB - In these studies we show that introduction of a normal human chromosome 6 or 6q can suppress the immortal phenotype of simian virus 40-transformed human fibroblasts (SV/HF). Normal human fibroblasts have a limited life span in culture. Immortal clones of SV/HF displayed nonrandom rearrangements in chromosome 6. Single human chromosomes present in mouse/human monochromosomal hybrids were introduced into SV/HF via microcell fusion and maintained by selection for a dominant selectable marker gpt, previously integrated into the human chromosome. Clones of SV/HF cells bearing chromosome 6 displayed limited potential for cell division and morphological characteristics of senescent cells. The loss of chromosome 6 from the suppressed clones correlated with the reappearance of immortal clones. Introduced chromosome 6 in the senescing cells was distinguished from those of parental cells by the analysis for DNA sequences specific for the donor chromosome. Our results further show that suppression of immortal phenotype in SV/HF is specific to chromosome 6. Introduction of individual human chromosomes 2, 8, or 19 did not impart cellular senescence in SV/HF. In addition, introduction of chromosome 6 into human glioblastoma cells did not lead to senescence. Based upon these results we propose that at least one of the genes (SEN6) for cellular senescence in human fibroblasts is present on the long arm of chromosome 6. PMID- 8202518 TI - Stable DNA transformation in the obligate intracellular parasite Toxoplasma gondii by complementation of tryptophan auxotrophy. AB - The protozoan parasite Toxoplasma gondii infects a wide range of vertebrate hosts and is an important opportunistic pathogen in immunocompromised humans. Although Toxoplasma is amenable to both biochemical and cellular experimental approaches, the molecular basis of its success as an intracellular parasite is poorly understood. To provide a system for molecular genetic analyses, we have developed a stable DNA transformation system for Toxoplasma based on complementation of its naturally occurring tryptophan auxotrophy. Complementation was accomplished by expressing the Escherichia coli trpB gene, encoding the beta subunit of tryptophan synthase (EC 4.2.1.20), the enzyme that catalyzes the formation of tryptophan from indole plus serine. Transformants were obtained by electroporation of a plasmid, called SAG1/trpB, containing the trpB gene flanked by Toxoplasma surface antigen 1 (SAG1) gene sequences and selection for growth on indole. Transformants were obtained with circular forms of the SAG1/trpB plasmid with efficiencies of 10(-4) per cell. Transformation with either circular or linear SAG1/trpB resulted in integration into the genome at distinct, nonhomologous sites. Trp+ transformants typically contained tandemly repeated copies of the SAG1/trpB plasmid and were stable in the absence of continued selection. The Trp phenotype provides a dominant selectable marker that should allow expression of foreign or altered genes in Toxoplasma and facilitate molecular analyses of genes important for intracellular survival. PMID- 8202517 TI - Suppression of Myc, but not E1a, transformation activity by Max-associated proteins, Mad and Mxi1. AB - Mad and Mxi1, two members of the Myc-related basic-region helix-loop helix/leucine-zipper family of proteins, associate directly with Max to form sequence-specific DNA binding heterodimers that are transactivation-incompetent. Mad-Max complexes have been shown to exert a strong repressive effect on Myc induced transactivation, perhaps through the competitive occupation of common promoter binding sites also recognized by active Myc-Max heterodimers. To place these recent biochemical observations in a biological context, mad and mxi1 expression vectors were tested for their ability to influence Myc transformation activity in the rat embryo fibroblast cooperation assay. Addition of an equimolar amount of mad or mxi1 expression vector to mouse c-myc/ras cotransfections resulted in a dramatic reduction in both the number of foci generated and the severity of the malignant phenotype. Myc-specific suppression by Mad and Mxi1 was demonstrated by their ability to affect c- and N-myc-, but not ela-, induced transformation. In contrast, mad and mxi1 expression constructs bearing deletions in the basic region exerted only mild repressive effects on Myc transformation activity, suggesting that occupation of common DNA binding sites by transactivation-incompetent Mad-Max or Mxi1-Max complexes appears to play a more dominant role in this suppression than titration of limited intracellular pools of Max away from active Myc-Max complexes. Thus, these biological data support a current model for regulation of Myc function in which relative intracellular levels of Mad and Mxi1 in comparison to those of Myc may determine the degree of activation of Myc-responsive growth pathways. PMID- 8202519 TI - Three tumor-suppressor regions on chromosome 11p identified by high-resolution deletion mapping in human non-small-cell lung cancer. AB - Non-small-cell lung cancer is the leading cause of cancer death for men and women in the industrialized nations. Identification of regions for genes involved in its pathogenesis has been difficult. Data presented here show three distinct regions identified on chromosome 11p. Two regions on 11p13 distal to the Wilms tumor gene WT1 and on 11p15.5 between the markers HBB and D11S860 are described. The third region on the telomere of 11p15.5 has been previously described and is further delineated in this communication. By high-resolution mapping the size of each of these regions was estimated to be 2-3 megabases. The frequency of somatic loss of genetic information in these regions (57%, 71%, and 45%, respectively) was comparable to that seen in heritable tumors such as Wilms tumor (55%) and retinoblastoma (70%) and suggests their involvement in pathogenesis of non-small cell lung cancer. Gene dosage analyses revealed duplication of the remaining allele in the majority of cases in the 11p13 and the proximal 11p15.5 region but rarely in the distal 11p15.5 region. In tumors with loss of heterozygosity in all three regions any combination of duplication or simple deletion was observed, suggesting that loss of heterozygosity occurs independently and perhaps at different points in time. These results provide a basis for studies directed at cloning potential tumor-suppressor genes in these regions and for assessing their biological and clinical significance in non-small-cell lung cancer. PMID- 8202520 TI - Molecular mapping of the heparin-binding exosite of thrombin. AB - Thrombin contains electropositive patches at opposite poles of the molecule which represent potential exosites for the binding of macromolecular ligands. The function of anion-binding exosite I, the fibrin(ogen) recognition site, has been well described. Anion-binding exosite II, located near the carboxyl terminus of the molecule, has been proposed to bind heparin on the basis of chemical modification studies. To define the functional heparin-binding site on thrombin, purified recombinant alpha-thrombins were prepared with glutamic acid substitution for selected basic amino acid residues in exosite II or exosite I. Heparin affinity was assessed by NaCl gradient elution from heparin-agarose, and second-order rate constants for inhibition by antithrombin III were determined in the absence and presence of heparin. Affinity for heparin-agarose was reduced markedly by selected mutations in exosite II (R89E, R245E, K248E, and K252E, numbered from the amino terminus of the B chain) but not by other mutations in exosite II (K174E, K247E) or by mutations in exosite I (R68E, K154E). All recombinant thrombins had similar rate constants for inhibition by antithrombin III without heparin. However, affinity for heparin-agarose correlated directly with the rate of inhibition by antithrombin III with heparin. These results demonstrate that selected mutations in anion-binding exosite II define a functional heparin-binding site and support the template mechanism of heparin action. PMID- 8202521 TI - MYCN is retained in single copy at chromosome 2 band p23-24 during amplification in human neuroblastoma cells. AB - Amplification of the human N-myc protooncogene, MYCN, is frequently seen either in extrachromosomal double minutes or in homogeneously staining regions of aggressively growing neuroblastomas. MYCN maps to chromosome 2 band p23-24, but homogeneously staining regions have never been observed at this band, suggesting transposition of MYCN during amplification. We have employed fluorescence in situ hybridization to determine the status of MYCN at 2p23-24 in five human neuroblastoma cell lines. All five lines carried, in addition to amplified MYCN in homogeneously staining regions or double minutes, single-copy MYCN at the normal position. In one line there was coamplification of MYCN together with DNA of the host chromosome 12, to which MYCN had been transposed. Our results suggest a model of amplification where MYCN is retained at its original location. They further sustain the view that either the initial events of MYCN amplification or the further evolution of amplified MYCN copies follow mechanisms different from those leading to amplification of drug-resistance genes. PMID- 8202522 TI - Immortalized germ cells undergo meiosis in vitro. AB - Establishing mammalian germ-cell lines capable of differentiation in vitro would greatly facilitate the study of gametogenesis and the meiotic process that is so fundamental for reproduction and the maintenance of genetic diversity of the species. We have established two germ-cell lines [GC-2spd(ts) and GC-3spc(ts)] by cotransfecting primary mouse testicular germ cells with the simian virus 40 large tumor antigen gene and the gene coding for a temperature-sensitive mutant of p53. Both cell lines express the germ cell-specific lactate dehydrogenase C4 isozyme and cytochrome ct isoform. At the permissive temperature of 37 degrees C, the GC 2spd(ts) line generates cells with a haploid DNA content and morphologic and biochemical features of round spermatids, including the appearance of an acrosomic granule. The identification of a flagellar axoneme when these cells are cultured at 32 degrees C further indicates that these cells correspond to the early spermatid stages of spermiogenesis. PMID- 8202523 TI - Identification of plant genetic loci involved in a posttranscriptional mechanism for meiotically reversible transgene silencing. AB - Numerous reports describe phenomena of transgene silencing in plants, yet the underlying genetic and molecular mechanisms are poorly understood. We observed that regeneration of Arabidopsis thaliana plants transgenic for the rolB gene of Agrobacterium rhizogenes results in a selection for transgene silencing. Transgene silencing could be monitored in this system by reversion of the visible RolB phenotype. We report a phenotypic, molecular, and genetic characterization of a meiotically reversible transgene silencing phenomenon observed in a rolB transgenic line. In this line, the rolB gene is expressed strongly and uniformly in seedlings, but in the course of further development, the rolB gene is silenced erratically at a frequency that depends on the dosage of rolB. The silenced state is mitotically stable, while complete resetting of rolB gene expression occurs in seedlings of the following generation. The silencing of rolB correlates with a dramatic reduction of steady-state rolB transcripts, while rolB nuclear run-off transcripts are only moderately reduced. Therefore, rolB gene silencing seems to act predominantly at the posttranscriptional level. The process of rolB gene silencing was found to be affected by two extragenic modifier loci that influence both the frequency and the timing of rolB gene silencing during plant development. These genetic data demonstrate a direct involvement of defined plant genes in this form of gene silencing. PMID- 8202524 TI - Alterations in major histocompatibility complex association of myocarditis induced by coxsackievirus B3 mutants selected with monoclonal antibodies to group A streptococci. AB - Three monoclonal antibodies (mAbs), 49.8.9, 36.2.2, and 54.2.8, made to the group A streptococcus M5 serotype identify crossreactive epitopes in cardiac tissues and also neutralize a highly myocarditic variant of coxsackievirus B3 (H3). Mutants of H3 were selected with these mAbs and evaluated for pathogenicity compared with the wild-type virus. H3 and the mutant variants selected with mAbs 36.2.2 (H3-36) and 54.2.8 (H3-54) induced severe myocarditis in DBA/2 (H-2d) and A/J (H-2a) male mice, whereas CBA (H-2k) mice were disease resistant. The virus variant isolated with mAb 49.8.9 (H3-49) was strikingly different and caused disease in CBA and A/J mice but not in DBA/2 animals, suggesting that the major histocompatibility complex association of the disease had been altered. This hypothesis was confirmed by using B10 congenic mice. In addition, T lymphocytes from the H3 and H3-49 virus-infected mice responded to distinctly different peptides in the streptococcal M protein, suggesting that certain epitopes of infectious agents which are shared with host tissues may be critical in determining disease susceptibility in genetically distinct individuals. PMID- 8202525 TI - Generation of a fusion partner to sample the repertoire of splenic B cells destined for apoptosis. AB - B cells proliferate and diversify in germinal centers in response to antigen. Only a small percentage of these B cells will emerge to form the serum antibody response. Other B cells making lower affinity antibodies, acquiring nonsense mutations, or expressing autoreactivity as a result of somatic mutation undergo an apoptotic cell death and are not efficiently sampled in current analyses of B cell hybridomas. We have demonstrated that expression of bcl-2 in the NSO myeloma fusion partner leads to a higher yield of viable hybridomas, with a selective increase in hybridomas from B cells that produce autoantibodies and are seldom recovered when spleen cells from non-autoimmune mice are fused to the conventional NSO cell line. Using this fusion partner, we have generated hybridomas from anti-DNA antibody-producing transgenic B cells that are anergic in vivo and destined for apoptosis. These studies provide a strategy to sample the repertoire of B cells that arise in vivo but are not selected to contribute to the expressed antibody response. Furthermore, they demonstrate that restricted expression of bcl-2 in B cells contributes to the maintenance of self-tolerance in secondary lymphoid organs. PMID- 8202526 TI - Selective inactivation of viruses in the presence of human platelets: UV sensitization with psoralen derivatives. AB - Inactivation of viruses in blood products requires that the method employed display selectivity in its action for viral elements while not affecting the biological entity of interest. Several methods have been developed for the treatment of human plasma or products derived from human plasma. An effective technique for the treatment of the cellular components of blood has been lacking, in part due to the inability to develop agents capable of selectively targeting viral agents in the milieu of cellular material. In this paper, we examine the behavior of a group of viral sensitizers designed to be added to cellular samples and be activated upon exposure to UVA light. Upon activation, these agents are capable of disrupting nucleic acids of the virus in a manner that renders them inactive for proliferation. The selectivity observed in this inactivation is determined by the chemical structure of the sensitizer, which can be varied to increase viral killing capacity while diminishing collateral damage to cellular and protein constituents. PMID- 8202527 TI - Human immunodeficiency virus type 1 may preferentially integrate into chromatin occupied by L1Hs repetitive elements. AB - Human DNA flanking sites of eight human immunodeficiency virus type 1 (HIV-1) proviral integrations have been analyzed in isolates derived both from integrations in an infected individual and from tissue culture. Sequence analysis encompassing 80-3000 bp of human DNA on one or both sides of the site of integration revealed that seven of the eight HIV-1 proviruses had integrated directly into or within one nucleosome's distance from an L1Hs or Alu repetitive element. To compare this with the frequency at which human L1 or Alu elements sharing > or = 70% identity with L1Hs and Alu consensus sequences would be encountered at random, > 200 bp from each of 82 individual anonymously cloned segments of human DNA were sequenced: L1Hs elements were encountered in 8.5% of the 82 clones and Alu elements were encountered in 13.4+ by using these homology windows. From these data it appears that HIV-1 integrates into or near L1Hs elements with an approximately 6-fold higher frequency than would be expected if HIV-1 integration events were distributed uniformly throughout the genome. A cumulative binomial probability test shows that there is a 0.26% chance that one would arrive at these figures by chance and puts the data well within a 99% confidence interval. We propose that sites of L1Hs and Alu insertions originally occurred in regions of chromatin that were more easily accessible to the retroposon machinery and that these regions are now acting as preferred integration sites for HIV-1. PMID- 8202528 TI - Role of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease. AB - The microtubule assembly-promoting activity of different pools of tau protein isolated from Alzheimer disease (AD) and control brains and the effect of dephosphorylation on this activity were studied. Tau isolated from a 2.5% perchloric extract of AD brain had almost the same activity as that obtained from control brain, and this activity did not change significantly on dephosphorylation. Abnormally phosphorylated tau (AD P-tau) isolated from brain homogenate of AD patients had little activity, and upon dephosphorylation with alkaline phosphatase, its activity increased to approximately the same level as the acid-soluble tau. Addition of AD P-tau to a mixture of normal tau and tubulin inhibited microtubule assembly. AD P-tau bound to normal tau but not to tubulin. These studies suggest that the abnormal phosphorylation of tau might be responsible for the breakdown of microtubules in affected neurons in AD not only because the altered protein has little microtubule-promoting activity but also because it interacts with normal tau, making the latter unavailable for promoting the assembly of tubulin into microtubules. PMID- 8202529 TI - Defective muscle basement membrane and lack of M-laminin in the dystrophic dy/dy mouse. AB - M-laminin is a major member of the laminin family of basement membrane proteins. It is prominently expressed in striated muscle and peripheral nerve. M-laminin is deficient in patients with the autosomal recessive Fukuyama congenital muscular dystrophy but is normal in patients with the sex-linked Duchenne and Becker muscular dystrophies. We have examined M-laminin expression in mice with autosomal recessive muscular dystrophy caused by the mutation dy. The heavy chain of M-laminin was undetectable in skeletal muscle, heart muscle, and peripheral nerve by immunofluorescence and immunoblotting in homozygous dystrophic dy/dy mice but was normal in heterozygous and wild-type nondystrophic mice. Immunofluorescence confirmed the presence of other major basement membrane proteins in the dystrophic mice. Very low levels of M-laminin heavy chain mRNA were detected by Northern blotting of muscle and heart tissue from dy/dy mice, suggesting that M-laminin heavy-chain mRNA may be produced at very low levels or is unstable. Information about the chromosomal localization of the M heavy-chain in human and mouse suggests that a mutation in the M-chain gene causes the muscular dystrophy in dy/dy mice. The dy mouse may provide a model for autosomal muscular dystrophies in humans and facilitate studies of functions of M-laminin. PMID- 8202530 TI - Structural and mechanistic characteristics of dihydropteridine reductase: a member of the Tyr-(Xaa)3-Lys-containing family of reductases and dehydrogenases. AB - Dihydropteridine reductase (EC 1.6.99.7) is a member of the recently identified family of proteins known as short-chain dehydrogenases. When the x-ray structure of dihydropteridine reductase is correlated with conserved amino acid sequences characteristic of this enzyme class, two important common structural regions can be identified. One is close to the protein N terminus and serves as the cofactor binding site, while a second conserved feature makes up the inner surface of an alpha-helix in which a tyrosine side chain is positioned in close proximity to a lysine residue four residues downstream in the sequence. The main function of this Tyr-Lys couple may be to facilitate tyrosine hydroxyl group participation in proton transfer. Thus, it appears that there is a distinctive common mechanism for this group of short-chain or pyridine dinucleotide-dependent oxidoreductases that is different from their higher molecular weight counterparts. PMID- 8202531 TI - Tyrosine kinase-deficient mutant human insulin receptors (Met1153-->Ile) overexpressed in transfected rat adipose cells fail to mediate translocation of epitope-tagged GLUT4. AB - Insulin regulates essential pathways for growth, differentiation, and metabolism in vivo. We report a physiologically relevant system for dissecting the molecular mechanisms of insulin signal transduction related to glucose transport. This is an extension of our recently reported method for transfection of DNA into rat adipose cells in primary culture. In the present work, cDNA coding for GLUT4 with an epitope tag (HA1) in the first exofacial loop is used as a reporter gene so that GLUT4 translocation can be studied exclusively in transfected cells. Insulin stimulates a 4.3-fold recruitment of transfected epitope-tagged GLUT4 to the cell surface. Cells cotransfected with the reporter gene and the human insulin receptor gene show an increase in cell surface GLUT4 in the basal state (no insulin) to levels comparable to those seen with maximal insulin stimulation of cells transfected with the reporter gene alone. In contrast, cells overexpressing a naturally occurring tyrosine kinase-deficient mutant insulin receptor (Met1153- >Ile) show no increase in the basal cell surface GLUT4 and no shift in the insulin dose-response curve relative to cells transfected with the reporter gene alone. These results demonstrate that insulin receptor tyrosine kinase activity is essential in insulin-stimulated glucose transport in adipose cells. PMID- 8202532 TI - Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. AB - Mice homozygous for a disrupted granulocyte/macrophage colony-stimulating factor (GM-CSF) gene develop normally and show no major perturbation of hematopoiesis up to 12 weeks of age. While most GM-CSF-deficient mice are superficially healthy and fertile, all develop abnormal lungs. There is extensive peribronchovascular infiltration with lymphocytes, predominantly B cells. Alveoli contain granular eosinophilic material and lamellar bodies, indicative of surfactant accumulation. There are numerous large intraalveolar phagocytic macrophages. Some mice have subclinical lung infections involving bacterial or fungal organisms, occasionally with focal areas of acute purulent inflammation or lobar pneumonia. Some features of this pathology resemble the human disorder alveolar proteinosis. These observations indicate that GM-CSF is not essential for the maintenance of normal levels of the major types of mature hematopoietic cells and their precursors in blood, marrow, and spleen. However, they implicate GM-CSF as essential for normal pulmonary physiology and resistance to local infection. PMID- 8202533 TI - Selection of multiple human immunodeficiency virus type 1 variants that encode viral proteases with decreased sensitivity to an inhibitor of the viral protease. AB - Inhibitors of the human immunodeficiency virus type 1 (HIV-1) protease represent a promising addition to the available agents used to inhibit virus replication in a therapeutic setting. HIV-1 is capable of generating phenotypic variants in the face of a variety of selective pressures. The potential to generate variants with reduced sensitivity to a protease inhibitor was examined by selecting for virus growth in cell culture in the presence of the protease inhibitor A-77003. Virus variants grew out in the presence of the inhibitor, and these variants encoded proteases with reduced sensitivity to the inhibitor. Variants were identified that encoded changes in each of the three subsites of the protease that interact with the inhibitor. HIV-1 displays significant potential for altering its interaction with this protease inhibitor, suggesting the need for multiple protease inhibitors with varying specificities. PMID- 8202534 TI - Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure. AB - Human serum amyloid P component (SAP) is a normal plasma protein and the precursor of amyloid P component (AP), a universal constituent of the abnormal tissue deposits in amyloidosis, including Alzheimer disease. We show here that its single N-linked biantennary oligosaccharide does not display the microheterogeneity usually characteristic of glycoproteins. The protein and the glycan structures of AP were also invariant, their resistance to degradation suggesting a role in persistence of amyloid deposits. Asialo-SAP was rapidly cleared from the circulation in mice by a mechanism dependent on terminal galactose residues and was catabolized in hepatocytes. However blockade of this pathway did not affect the clearance of native SAP. Rapid hepatic uptake and catabolism of human asialo-SAP in man were also directly demonstrated. The protein and glycan homogeneity of SAP and the integrity of AP suggest that the complete glycoprotein structure is important for the normal and the pathophysiological functions of this molecule. PMID- 8202535 TI - Cloning and expression of a cDNA encoding a brain-specific Na(+)-dependent inorganic phosphate cotransporter. AB - We have isolated a brain-specific cDNA that encodes a Na(+)-dependent inorganic phosphate (Pi) cotransporter (BNPI). The nucleotide sequence of BNPI predicts a protein of 560 amino acids with 6-8 putative transmembrane-spanning segments that is approximately 32% identical to the rabbit kidney Na(+)-dependent Pi cotransporter. Expression of BNPI mRNA in Xenopus oocytes results in Na(+) dependent Pi transport similar to that reported for the recombinantly expressed or native kidney Na(+)-dependent cotransporter. RNA blot analysis reveals that BNPI mRNA is expressed predominantly (if not exclusively) in brain, and in situ hybridization histochemistry reveals BNPI transcripts in neurons of the cerebral cortex, hippocampus, and cerebellum. Furthermore, we have confirmed the presence of saturable Na(+)-dependent Pi cotransport in cultured cerebellar granule cells. Together, these data demonstrate the presence of a specific neuronal Na(+) dependent transport system for Pi in brain. PMID- 8202536 TI - Proton conduction within the reaction centers of Rhodobacter capsulatus: the electrostatic role of the protein. AB - Light-induced charge separation in the photosynthetic reaction center results in delivery of two electrons and two protons to the terminal quinone acceptor QB. In this paper, we have used flash-induced absorbance spectroscopy to study three strains that share identical amino acid sequences in the QB binding site, all of which lack the protonatable amino acids Glu-L212 and Asp-L213. These strains are the photosynthetically incompetent site-specific mutant Glu-L212/Asp-L213-->Ala L212/Ala-L213 and two different photocompetent derivatives that carry both alanine substitutions and an intergenic suppressor mutation located far from QB (class 3 strain, Ala-Ala + Arg-M231-->Leu; class 4 strain, Ala-Ala + Asn-M43- >Asp). At pH 8 in the double mutant, we observe a concomitant decrease of nearly 4 orders of magnitude in the rate constants of second electron and proton transfer to QB compared to the wild type. Surprisingly, these rates are increased to about the same extent in both types of suppressor strains but remain > 2 orders of magnitude smaller than those of the wild type. In the double mutant, at pH 8, the loss of Asp-L213 and Glu-L212 leads to a substantial stabilization (> or = 60 meV) of the semiquinone energy level. Both types of compensatory mutations partially restore, to nearly the same level, the original free energy difference for electron transfer from primary quinone QA to QB. The pH dependence of the electron and proton transfer processes in the double-mutant and the suppressor strains suggests that when reaction centers of the double mutant are shifted to lower pH (1.5-2 units), they function like those of the suppressor strains at physiological pH. Our data suggest that the main effect of the compensatory mutations is to partially restore the negative electrostatic environment of QB and to increase an apparent "functional" pK of the system for efficient proton transfer to the active site. This emphasizes the role of the protein in tuning the electrostatic environment of its cofactors and highlights the possible long-range electrostatic effects. PMID- 8202537 TI - Spatial distribution of two maternal messengers in Paracentrotus lividus during oogenesis and embryogenesis. AB - We demonstrated that two mRNAs that are synthesized during the vitellogenic period of oogenesis and that code for cell surface proteins are asymmetrically distributed in the unfertilized egg of Paracentrotus lividus. At fertilization, these RNAs rapidly localize in the cortical zone at the animal pole of the egg. They are then detected in the mesomeres and the macromeres, but not in the micromeres, and thereafter are found in the ectoderm but not in the vegetal plate, mesenchyme cells, or early intestine. They disappear in late gastrula. The proteins synthesized by these mRNAs show the same territorial location during the period examined here, which included the unfertilized egg and the 16-blastomere stage. These conclusions were reached on the basis of in situ hybridization and immunostaining experiments, as well as Northern and Western blot analyses of isolated blastomeres. The possible significance of this asymmetric distribution of these two mRNAs and proteins in the establishment of the animal/vegetal axis is discussed. PMID- 8202538 TI - Specific T-cell tolerance may be preceded by a primary response. AB - We have evaluated the ability of ovalbumin to induce T-cell-specific tolerance in SJL mice. A significant decrease of interleukin 2 in lymph-node culture supernatants from tolerant mice upon antigen stimulation was seen. Oral tolerization was less effective than i.p.- or s.c.-tolerization protocols. Transfer experiments of either splenic or lymph-node T cells from tolerant mice to naive mice definitely ruled out suppression as a mechanism involved in tolerant mice. Surprisingly, we found that, before the establishment of specific T-cell tolerance to ovalbumin, T cells from mice that will display tolerance were responsive and synthesized interleukin 2 upon antigen challenge in vitro. Thus, we concluded that anergy cannot account solely for the T-cell unresponsiveness in tolerant mice. Furthermore, although we cannot rule out the hypothesis that the T cell unresponsiveness in tolerant mice can be explained by programmed cell death of ovalbumin-specific T cells, these data led us to speculate that T-cell "refractoriness" could explain the drop of interleukin 2 production in lymph-node T-cell culture supernatant from tolerant mice. PMID- 8202539 TI - A synthetic retinoid antagonist inhibits the human immunodeficiency virus type 1 promoter. AB - Retinoids regulate a broad range of biological processes and affect cell growth and differentiation of many cell types, including the immune system. Recently, it was reported that human immunodeficiency virus type 1 (HIV-1) expression in macrophages is enhanced by retinoic acid (RA). Retinoid signals are mediated by the RA receptors (RARs) and retinoid X receptors (RXRs) that bind to specific RA responsive elements (RAREs) in the promoter region of susceptible genes. Here, we report on a RARE in the long terminal repeat (LTR) region that allows activation of the HIV-1 LTR. The RARE is composed of two consensus RARE half-sites (A/GGGTCA) arranged as a palindrome separated by 9 nucleotides and is activated by both RAR/RXR heterodimers and RXR homodimers. We show that the COUP (chicken ovalbumin upstream promoter) orphan receptors also bind to the HIV-1 RARE and repress the retinoid response of the HIV-1 RARE or the HIV-1 LTR. Furthermore, a newly discovered synthetic retinoid is shown to be a potent inhibitor of retinoid induced activation of the HIV-1 RARE. These observations suggest additional approaches for the inhibition of HIV replication. PMID- 8202540 TI - The animal model of human amnesia: long-term memory impaired and short-term memory intact. AB - Normal monkeys and monkeys with lesions of the hippocampal formation and adjacent cortex (the H+ lesion) were trained on the delayed nonmatching to sample (DNMS) task with a delay of 0.5 s between the sample and the choice. The animals with H+ lesions learned the task normally at this short delay and also exhibited the same pattern of response latencies as normal monkeys. This finding contrasts with previous observations that initial learning of the DNMS task with delays of 8-10 s is impaired after H+ lesions. The absence of an impairment at a delay of 0.5 s indicates that the H+ lesion does not affect short-term memory. In contrast, when monkeys with H+ lesions were tested at longer delays (> 30 s), an impairment was observed. This selective impairment occurred when the delays were presented sequentially (from 0.5 s to 10 min) and also when delays were presented in a mixed order (1 s, 1 min, and 10 min). The data indicate that the H+ lesion produces a selective impairment in long-term memory, in the absence of a detectable deficit in short-term memory or perception. Accordingly, the findings confirm the long-standing idea, based primarily on studies of humans, that short term memory is independent of medial temporal lobe function. The findings thereby establish an important parallel between memory impairment in monkeys and humans and provide additional support for the validity of the animal model of human amnesia in the monkey. PMID- 8202541 TI - Expansion of CREB's DNA recognition specificity by Tax results from interaction with Ala-Ala-Arg at positions 282-284 near the conserved DNA-binding domain of CREB. AB - The transactivator protein of human T-lymphotropic virus type I (HTLV-I), Tax, forms multiprotein complexes with the ubiquitous transcription factor CREB and the CREB/ATF-1 heterodimer. The interaction between Tax and CREB is highly specific and results in increased binding of the Tax/CREB complexes to the HTLV-I 21-bp repeats. Despite the extensive sequence similarities between CREB and ATF 1, Tax interacts with ATF-1 only marginally. Compared with CREB, Tax/CREB exhibits greatly increased DNA recognition specificity and preferentially assembles on a consensus binding site, GGGGG(T/A)TGACG(T/C)(A/C)TA(T/C)C-CCCC, homologous to the HTLV-I 21-bp repeats. Here we report that Tax affects CREB binding to the Tax-inducible DNA elements by interacting with the basic-leucine zipper (bZip) domain of CREB. We show by domain switching that the basic region in CREB bZip can confer on c-Jun and ATF-1 leucine zippers the ability to interact with Tax in vitro. Mutational analyses further demonstrate that the amino acid residues of CREB critical for Tax/CREB interaction are Ala-Ala-Arg at positions 282-284 (AAR284), immediately upstream of the highly conserved DNA binding domain (R/K)XX(R/K) N(R/K)XAAXX(S/C)RX(R/K)(K/R) characteristic of all bZip proteins. Specific amino acid substitutions in AAR284 of CREB weakened or abolished Tax/CREB interaction, whereas reciprocal changes in ATF-1 allowed it to interact with Tax. These results support a model in which the specific interaction between Tax and the AAR284 residues near the DNA-binding domain of CREB results in a multiprotein complex with altered DNA recognition property. This protein complex assembles selectively on the viral Tax-responsive 21-bp repeats to augment transcription. PMID- 8202542 TI - Targeted mutation of the CREB gene: compensation within the CREB/ATF family of transcription factors. AB - The cAMP response element binding protein (CREB) has been implicated as a key regulator in the transcriptional control of many genes. To assess the functional importance of CREB in vivo and its role in development, we used gene targeting to generate mice with a disruption of the CREB gene. Homozygous mutant mice appeared healthy and exhibited no impairment of growth or development. In this report we demonstrate that CREB and two other members of the CREB/ATF family, cAMP response element modulation protein (CREM) and activating transcription factor 1 (ATF1), appear to form a unique subgroup within this extensive class of transcription factors. Examination of CREM mRNA and protein levels in CREB mutant mice demonstrated overexpression of CREM in all tissues examined, but no change in ATF1 levels. These data demonstrate that CREB is not the sole mediator of cAMP dependent transcriptional regulation and probably acts in concert with a specific subset of cAMP response element-binding proteins to transduce the cAMP signal and, in its absence, these same proteins can compensate for CREB function in vivo. PMID- 8202543 TI - Finding a needle in a haystack: detection of a small protein (the 12-kDa VP26) in a large complex (the 200-MDa capsid of herpes simplex virus). AB - Macromolecular complexes that consist of homopolymeric protein frameworks with additional proteins attached at strategic sites for a variety of structural and functional purposes are widespread in subcellular biology. One such complex is the capsid of herpes simplex virus type 1 whose basic framework consists of 960 copies of the viral protein, VP5 (149 kDa), arranged in an icosahedrally symmetric shell. This shell also contains major amounts of three other proteins, including VP26 (12 kDa), a small protein that is approximately equimolar with VP5 and accounts for approximately 6% of the capsid mass. With a view to inferring the role of VP26 in capsid assembly, we have localized it by quantitative difference imaging based on three-dimensional reconstructions calculated from cryo-electron micrographs. Purified capsids from which VP26 had been removed in vitro by treatment with guanidine hydrochloride were compared with preparations of the same depleted capsids to which purified VP26 had been rebound and with native (undepleted) capsids. The resulting three-dimensional density maps indicate that six VP26 subunits are distributed symmetrically around the outer tip of each hexon protrusion on VP26-containing capsids. Because VP26 may be readily dissociated from and reattached to the capsid, it does not appear to contribute significantly to structural stabilization. Rather, its exposed location suggests that VP26 may be involved in linking the capsid to the surrounding tegument and envelope at a later stage of viral assembly. PMID- 8202544 TI - D-MEF2: a MADS box transcription factor expressed in differentiating mesoderm and muscle cell lineages during Drosophila embryogenesis. AB - The myocyte enhancer factor (MEF) 2 family of transcription factors has been implicated in the regulation of muscle transcription in vertebrates. We have cloned a protein from Drosophila, termed D-MEF2, that shares extensive amino acid homology with the MADS (MCM1, Agamous, Deficiens, and serum-response factor) domains of the vertebrate MEF2 proteins. D-mef2 gene expression is first detected during Drosophila embryogenesis within mesodermal precursor cells prior to specification of the somatic and visceral muscle lineages. Expression of D-mef2 is dependent on the mesodermal determinants twist and snail but independent of the homeobox-containing gene tinman, which is required for visceral muscle and heart development. D-mef2 expression precedes that of the MyoD homologue, nautilus, and, in contrast to nautilus, D-mef2 appears to be expressed in all somatic and visceral muscle cell precursors. Its temporal and spatial expression patterns suggest that D-mef2 may play an important role in commitment of mesoderm to myogenic lineages. PMID- 8202546 TI - Cisplatin-DNA adducts are molecular decoys for the ribosomal RNA transcription factor hUBF (human upstream binding factor). AB - The toxicity of DNA-damaging agents is widely believed to result from the formation of lesions that block polymerases or disrupt the integrity of the genome. A mechanism heretofore not addressed is that DNA damage may titrate essential DNA-binding proteins away from their natural sites of action. This report shows that the ribosomal RNA (rRNA) transcription factor hUBF (human upstream binding factor) binds with striking affinity (Kd(app) approximately 60 pM) to the intrastrand cis-[Pt(NH3)2](2+-d(GpG) crosslink formed by the anticancer drug cis-diamminedichloroplatinum(II) (cisplatin). When protein blots of human cell extracts are probed with cisplatin-modified DNA, 97- and 94-kDa proteins are detected, consistent with the known sites of hUBF species. A similar analysis of blots containing in vitro translated hUBF confirmed that the protein binds cisplatin adducts with high specificity. By contrast, DNA adducts of the clinically ineffective trans isomer of cisplatin, trans diamminedichloroplatinum(II), are not recognized by hUBF. DNase I inhibition patterns of hUBF bound to a 100-base-pair DNA fragment containing a centrally located cis-[Pt(NH3)2](2+)-d(GpG) crosslink reveal specific protein-DNA interactions in a 14-base-pair region flanking the adduct. The affinity of hUBF for the rRNA promoter is similar (Kd(app) approximately 18 pM) to that measured for the cisplatin adduct. In addition, we observe that the hUBF-promoter interaction is highly sensitive to the antagonistic effects of cisplatin-DNA adducts. These results suggest that a cisplatin-mediated transcription-factor hijacking mechanisms could disrupt rRNA synthesis, which is stimulated in proliferating cells. PMID- 8202545 TI - Differences in dorsal and ventral pigmentation result from regional expression of the mouse agouti gene. AB - The agouti coat color gene encodes a paracrine signaling molecule that controls the production of yellow and black pigment by melanocytes within hair follicles. Some agouti alleles affect the dorsum and ventrum independently, which has provided the basis for speculation that agouti gene action in different regions of the body is controlled by distinct genetic loci that are closely linked. Using a combination of cDNA cloning and RNA expression studies, we find that alternative isoforms of agouti mRNA contain different noncoding first exons located 100 kb apart, whose patterns of expression indicate independent control by regulatory elements that are either ventral specific or hair cycle specific. These results demonstrate that the apparent genetic complexity of the agouti locus is explained by the existence of multiple regulatory elements exerting control over a single coding sequence and provide a conceptual basis for understanding differences in dorsal and ventral hair coloration in many mammalian species. The ventral-specific agouti isoform represents an example of a transcript whose expression is restricted to ventral skin and provide an approach to investigate the mechanisms by which dorsal-ventral differences in gene expression are established and maintained. PMID- 8202547 TI - Transcriptional down-regulation by insulin of the beta 3-adrenergic receptor expression in 3T3-F442A adipocytes: a mechanism for repressing the cAMP signaling pathway. AB - Modulation of the three beta-adrenergic receptor subtypes (beta-ARs) by insulin was investigated in mouse 3T3-F442A adipocytes. Saturation and competition experiments measuring binding of 125I-labeled (-)-cyanopindolol to adipocyte membranes demonstrated that cell exposure to insulin for 4 days caused a 3.5-fold decrease in the density of the major beta-AR component of the adipocyte, the beta 3-AR, while beta 1-AR sites remained unchanged and beta 2-ARs were undetectable. This correlated with a lower potency of the beta 3-AR-selective agonists CGP12177, ICI201651, and BRL37344 in stimulating adenylate cyclase. Northern blotting analysis indicated that insulin induced a rapid and sharp decrease in beta 3-AR mRNA levels. This effect was detectable at low insulin concentrations (EC50 = 3 nM) and was not observed in the presence of insulin-like growth factor I, suggesting an insulin receptor-mediated phenomenon. Reverse transcriptase-PCR analysis showed that, in contrast to its dramatic down-regulatory effect on beta 3-AR mRNA, insulin did not modify the levels of beta 1- and beta 2-AR transcripts. As assessed by nuclear run-on assays, insulin inhibited the beta 3 AR gene transcription rate by 90% within 30 min. mRNA turnover experiments showed that the half-life of beta 3-AR mRNA was short (90 min) and remained unaffected by insulin. These findings demonstrate the genetic control of a beta-AR subtype expression by insulin and reveal a mechanism for the regulation by this hormone of cAMP-dependent biological processes in adipocytes. PMID- 8202548 TI - Dynamic instability of microtubules as an efficient way to search in space. AB - During the formation of the mitotic spindle, dynamic microtubules search for chromosomes in the surrounding cytosol. The average time required to reach such "targets" is calculated within a simple model of dynamic instability. The values of the dynamic parameters that minimize this search time are also obtained. The results approximate well observations of the capture of chromosomes in prometaphase cells. Compared to usual reversible polymerization, dynamic instability reduces the time required to find a target by several orders of magnitude. PMID- 8202549 TI - Disruption of the Golgi apparatus by brefeldin A blocks cell polarization and inhibits directed cell migration. AB - The role of the Golgi apparatus in the motile activity of fibroblasts was examined with brefeldin A (BFA), which disrupts the Golgi apparatus in a variety of cells. Upon incubation with BFA, Swiss mouse 3T3 fibroblasts lost their typical polarized morphology, in which the leading edge is characterized by intensive lamellipodia formation. BFA affected cell asymmetry as demonstrated by a decrease in the morphometric indices, dispersion, and elongation. After BFA treatment, cells showed little protrusional activity and did not form a dense actin network at the leading edge, and consequently the rate of cell migration into an experimental wound was significantly reduced. In addition, BFA prevented an increase in pseudopodial activity and prevented the formation of long processes induced by phorbol 12-myristate 13-acetate. The effects of BFA on cell shape and protrusional activity were quantitatively similar to those observed with the microtubule-disrupting agent nocodazole, although BFA had no effect on microtubule integrity. These results suggest that the integrity of both the Golgi apparatus and microtubules is necessary for the generation and maintenance of fibroblast asymmetry, which is a prerequisite for directed cell migration. PMID- 8202550 TI - Effective amplification of long targets from cloned inserts and human genomic DNA. AB - We have used the polymerase chain reaction (PCR) to amplify up to 22 kb of the beta-globin gene cluster from human genomic DNA and up to 42 kb from phaga lambda DNA. We have also amplified 91 human genomic inserts of 9-23 kb directly from recombinant lambda plaques. To do this, we increased pH, added glycerol and dimethyl sulfoxide, decreased denaturation times, increased extension times, and used a secondary thermostable DNA polymerase that possesses a 3'-to 5' exonuclease, or "proofreading," activity. Our "long PCR" protocols maintain the specificity required for targets in genomic DNA by using lower levels of polymerase and temperature and salt conditions for specific primer annealing. The ability to amplify DNA sequences of 10-40 kb will bring the speed and simplicity of PCR to genomic mapping and sequencing and facilitate studies in molecular genetics. PMID- 8202551 TI - Macromolecular permeability across the blood-nerve and blood-brain barriers. AB - The permeability of insulin (Ins), nerve growth factor (NGF), albumin (Alb), transferrin (Trf), and IgG across the blood-nerve barrier (BNB) and blood-brain barrier (BBB) in normal adult rats was quantified by measuring the (permeability coefficient x surface area) product (PS) with the i.v. bolus-injection technique in the cannulated brachial vein and artery using radioiodinated proteins. The PS values of the BNB for IgG and Alb were low: 0.079 +/- 0.029 x 10(-6) and 0.101 +/ 0.088 x 10(-6) ml.g-1.s-1, (mean +/- SD, respectively). The PS values for NGF and Trf were 16.1-fold and 25.5-fold higher than for Alb. The PS for Ins across the BNB was 33.190 +/- 2.053 x 10(-6) ml.g-1.s-1--a remarkable 329-fold increase compared with Alb. The PS values of the BBB for IgG and Alb in different brain regions were all low, from 0.028 +/- 0.017 to 0.151 +/- 0.035 x 10(-6) ml.g-1.s-1 (mean +/- SD). NGF and Trf had comparable PS values from 13- to 32-fold higher than for Alb, except for the brain stem, where the PS for Trf was 66-fold higher than for Alb. The mean PS for Ins across the BBB ranged from 15.78 +/- 5.45 x 10( 6) ml.g-1.s-1 for the cortex to 22.62 +/- 7.50 x 10(-6) ml.g-1.s-1 for the brain stem--again a remarkable 105- to 390-fold increase relative to Alb. Because reliable PS measurements were obtained for all proteins tested, the BBB and BNB cannot be considered impermeable to proteins--a concept that has plagued brain- and nerve-barrier research. The low PS values for IgG and Alb indicate low rates of transfer; however, Alb, in particular, is the major protein of endoneurial and ventricular fluid, which suggests that these PS values may be significant. Ins had the highest PS values, which likely reflect the mechanism of transport across the barriers--that is, receptor-mediated transport. Because NGF and Trf had PS values 13- to 66-fold higher than for Alb, whether this reflects receptor mediated uptake, adsorptive-mediated transcytosis, or some other mechanism is unclear. That the PS values for NGF and Trf differ from Alb and IgG clearly suggests, however, a different uptake mechanism. Finally, the remarkably high PS values for Ins across the BBB and BNB identify this protein and its putative receptor on capillary endothelial cells as a potential target for drug delivery into the central and peripheral nervous systems. PMID- 8202552 TI - Advanced Maillard reaction end products are associated with Alzheimer disease pathology. AB - During aging long-lived proteins accumulate specific post-translational modifications. One family of modifications, termed Maillard reaction products, are initiated by the condensation between amino groups of proteins and reducing sugars. Protein modification by the Maillard reaction is associated with crosslink formation, decreased protein solubility, and increased protease resistance. Here, we present evidence that the characteristic pathological structures associated with Alzheimer disease contain modifications typical of advanced Maillard reaction end products. Specifically, antibodies against two Maillard end products, pyrraline and pentosidine, immunocytochemically label neurofibrillary tangles and senile plaques in brain tissue from patients with Alzheimer disease. In contrast, little or no staining is observed in apparently healthy neurons of the same brain. The Maillard-reaction-related modifications described herein could account for the biochemical and insolubility properties of the lesions of Alzheimer disease through the formation of protein crosslinks. PMID- 8202553 TI - Neurally expressed Drosophila genes encoding homologs of the NSF and SNAP secretory proteins. AB - Several lines of investigation have now converged to indicate that the neurotransmitter release apparatus is formed by assembly of cytosolic proteins with proteins of the synaptic vesicle and presynaptic terminal membranes. We are undertaking a genetic approach in Drosophila melanogaster to investigate the functions of two types of cytosolic proteins thought to function in this complex: N-ethylmaleimide-sensitive fusion protein (NSF) and the soluble NSF attachment proteins (SNAPs). We have identified Drosophila homologs of the vertebrate and yeast NSF and SNAP genes. Both Drosophila genes encode polypeptides that closely resemble their vertebrate counterparts and are expressed in the nervous system; neither appears to be in a family of closely related Drosophila genes. These results indicate that the Drosophila NSF and SNAP genes are excellent candidates for mutational analysis of neurotransmitter release. PMID- 8202555 TI - rbcL gene sequences provide evidence for the evolutionary lineages of leptosporangiate ferns. AB - Pteriodophytes have a longer evolutionary history than any other vascular land plant and, therefore, have endured greater loss of phylogenetically informative information. This factor has resulted in substantial disagreements in evaluating characters and, thus, controversy in establishing a stable classification. To compare competing classifications, we obtained DNA sequences of a chloroplast gene. The sequence of 1206 nt of the large subunit of the ribulose-bisphosphate carboxylase gene (rbcL) was determined from 58 species, representing almost all families of leptosporangiate ferns. Phlogenetic trees were inferred by the neighbor-joining and the parsimony methods. The two methods produced almost identical phylogenetic trees that provided insights concerning major general evolutionary trends in the leptosporangiate ferns. Interesting findings were as follows: (i) two morphologically distinct heterosporous water ferns, Marsilea and Salvinia, are sister genera; (ii) the tree ferns (Cyatheaceae, Dicksoniaceae, and Metaxyaceae) are monophyletic; and (iii) polypodioids are distantly related to the gleichenioids in spite of the similarity of their exindusiate soral morphology and are close to the higher indusiate ferns. In addition, the affinities of several "problematic genera" were assessed. PMID- 8202556 TI - The involvement of a Ca2+ channel blocking mode of action in the pharmacology of Ammi visnaga fruits. AB - Based on a screening program of medicinal plants for their possible calcium antagonistic mode of action, the most active lipophilic extract of Ammi visnaga fruits (DAB 10) was fractionated by CC and investigated pharmacologically at K+ (60 mM)-depolarized guinea-pig aortic strips. Visnadin, khellin, and visnagin were identified and determined as the effective principles in this testing model with the dihydropyranocoumarin visnadin being the most active. Further selectivity tests against norepinephrine (100 microM)-induced contractions evaluated a possible pharmacological differentiation between these compounds as the furanochromones khellin and visnagin inhibited both spasms to a similar extent while visnadin's activity was significantly higher against K(+)-spasms, suggesting an involvement of a calcium channel blocking mode of action for visnadin. PMID- 8202554 TI - Membrane repolarization stops caffeine-induced Ca2+ release in skeletal muscle cells. AB - We have combined the patch-clamp technique with fura-2 measurements to investigate whether the Ca(2+)-induced Ca(2+)-release channel is under the control of membrane potential in rat skeletal myoballs. We report that Ca2+ release induced by 10 mM caffeine is turned off by membrane repolarization, a phenomenon that we term RISC (repolarization-induced stop of Ca2+ release). The RISC phenomenon is voltage- and time-dependent. It is evident only when the release channels are first transferred into a functionally "voltage-activated" state through membrane depolarization. The results demonstrate that membrane repolarization actively closes the caffeine-activated release channels and suggest that the ryanodine receptor is actually the physiological depolarization induced Ca(2+)-release channel. Thus, our data provide compelling evidence for a bidirectional voltage control (depolarization and repolarization) of the Ca(2+) release channel in the sarcoplasmic reticulum by a voltage sensor in the transverse tubule membrane. PMID- 8202557 TI - Tea plant root extract (TRE) as an antineoplastic agent. AB - The antitumour effect of tea plant root extract (TRE) has been evaluated against Ehrlich ascites carcinoma (EAC) in Balb-C mice. Significant increases of survival times of the TRE-treated, tumour-bearing mice have been confirmed repeatedly with respect to the control group. TRE inhibited the tumour cell growth and reversed the changes of haematological parameters consequent to tumour inoculation. PMID- 8202558 TI - Protective effects of Mikania cordata root extract against physical and chemical factors-induced gastric erosions in experimental animals. AB - The effect of the methanolic fraction of Mikania cordata (Burm., B. L. Robinson) root extract was investigated for its possible ulceroprotective activity in male Sprague-Dawley rats. Oral administration of this extract (50, 100, or 150 mg/kg) significantly prevented the occurrence of water immersion stress-induced gastric ulcers in a dose-responsive manner. The extract also dose-dependently inhibited gastric ulcers induced by ethanol, aspirin, and phenylbutazone. The ED50 values of the extract in the above four ulcer models were found to be 95.1, 109.7, 125.5, and 136.2 mg/kg, respectively. The volume, acidity, and peptic activity of the gastric juice in pylorous-ligated rats were not altered upon administration of the extract (100 or 150 mg/kg) but it significantly and dose-dependently promoted the gastric mucus secretion in normal as well as stress- and ethanol induced ulcerated animals. Based on these results, we conclude that M. cordata root extract possesses antiulcer activity and that the observed activity may be due to the modulation of defensive factors through an improvement of gastric cytoprotection. PMID- 8202559 TI - Effects of Nardostachys jatamansi on biogenic amines and inhibitory amino acids in the rat brain. AB - The effect of acute and subchronic administration of an alcoholic extract of the roots of Nardostachys jatamansi on norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), gamma-aminobutyric acid (GABA), and taurine were studied in male albino Wistar rats. The acute oral administration of the extract did not change the level of NE and DA but resulted in a significant increase in the level of 5-HT and 5-HIAA. A significant increase in the level of GABA and taurine was observed in the drug-treated groups when compared to the controls. A 15-day treatment resulted in a significant increase in the levels of NE, DA, 5-HT, 5-HIAA, and GABA. These data indicate that the alcoholic extract of the roots of N. jatamansi causes an overall increase in the levels of central monoamines and inhibitory amino acids. PMID- 8202560 TI - Antiulcer action of Styrax camporum and Caesalpinia ferrea in rats. '. AB - Stem extracts of Styrax camporum Pohl and Caesalpinia ferrea Martius were administered orally and intraperitoneally to rats and effected a decrease in the acute ulceration number. The volume, pH, and hydrochloric acid concentration of gastric secretions were measured after administration of both extracts, atropine, and cimetidine. After oral administration there was a decrease in the gastric secretion volume without modification of the other gastric secretion parameters studied. There were modifications, however, when the extracts were administered intraperitoneally. Analgesy, influence on sleeping time, and spontaneous motor activity test results indicate a probable absence of central action components in the extracts. PMID- 8202561 TI - An antileishmanial chalcone from Chinese licorice roots. AB - A bioassay guided fractionation of an extract of Chinese licorice roots led to the isolation of (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-[4- hydroxy 3-(3-methyl-2-butenyl]phenyl-2-propen-1-one, which in vitro showed potent antileishmanial activity. In addition, the novel chalcone (E)-1-[2,4-dihydroxy-3 (3-methyl-2- butenyl)phenyl]-3-(2,2-dimethyl-8-hydroxy-2H-benzopyran-6-yl)-2 prope n-1-one was isolated from the roots. The latter compound only showed antileishmanial activity at high concentrations. PMID- 8202562 TI - Studies on anti-allergic components in the roots of Asiasarum sieboldi. AB - The methanolic extract of the roots of Asiasarum sieboldi has been evaluated for anti-allergic effects on various experimental models in vitro and in vivo. Bioassay-guided fractionation of the methanolic extract resulted in isolation of suppressive compounds in the PCA test: methyleugenol (1), elemicin (2), gamma asarone (3), (-)-asarinin (4), and (-)-sesamin (5). Furthermore, elemicin (2) and (2E,4E,8Z,10E)-N-isobutyl-2,4,8,10-dodecatetraenami de (6) were found to exhibit an inhibitory action on 5-lipoxygenase (5-LOX) from RBL-1 cells. 3',4' Dimethoxycinnamaldehyde (7) and xanthoxylol (8) potently reduced the contractile response of guinea pig ileal strips to LTD4. PMID- 8202563 TI - Fatty acids and other compounds with nematicidal activity from cultures of Basidiomycetes. AB - In a screening for nematicidal activities in cultures of Basidiomycetes, cultures of Pleurotus pulmonarius and Hericium coralloides exhibited toxic effects towards the saprophytic nematode Caenorhabditis elegans. Subsequently S-coriolic acid (1), linoleic acid (2), p-anisaldehyde (3), p-anisyl alcohol (4), 1-(4 methoxyphenyl)-1,2-propanediol (5), and 2-hydroxy-(4'-methoxy)-propiophenone (6) were isolated from submerged cultures of P. pulmonarius. All compounds showed nematicidal activities towards C. elegans. The most active compounds were 1 and 2 with LD50 values between 5 and 10 ppm. Compounds 1, 4, and 5 have not been previously isolated from higher fungi, 6 is a new natural product. From cultures of H. coralloides, which exhibited both repellant and nematicidal effects, a nematicidal fatty acid mixture was obtained, containing linoleic acid, oleic acid, and palmitic acid as its main components. PMID- 8202564 TI - Influence of asiatic acid, madecassic acid, and asiaticoside on human collagen I synthesis. AB - Asiatic acid, madecassic acid, and asiaticoside, terpenoids with an ursane skeleton, were tested separately and in combination on skin human fibroblast collagen I synthesis in vitro. In the absence of ascorbic acid, the mixture as well as each individual component stimulated collagen I synthesis to a similar extent. In the presence of ascorbic acid, the level of collagen I secretion was higher for each individual component and for the mixture. A comparison of asiaticoside and asiatic acid shows that the sugar moiety of the molecule does not seem to be necessary for this biological activity. PMID- 8202565 TI - A comparison of the antihepatotoxic activity between glycyrrhizin and glycyrrhetinic acid. AB - A comparison of antihepatotoxic activities between glycyrrhizin (18 beta-GL) and its genuine aglycone, glycyrrhetinic acid (18 beta-GA), was carried out using in vivo and in vitro assay methods. The oral administration of 18 beta-GA at 1, 24, and 48 h before D-galactosamine (GalN) treatment significantly reduced the increase of serum transaminase activities 24 h after GalN treatment, whereas 18 beta-GL did not inhibit the increase of serum transaminase activities. The intraperitoneal administration of 18 beta-GA 1 h before GalN treatment restored the increase of serum transaminase activities with lower doses than 18 beta-GL. In CCl4-induced cytotoxicity of primary cultured rat hepatocytes, 18 beta-GA protected the CCl4-induced leakage of transaminase at doses of 5 to 50 micrograms/ml, whereas 18 beta-GL inhibited slightly the leakage at a dose of 1000 micrograms/ml. In the same way, 18 alpha-GA, the alpha-isomer of 18 beta-GA, reduced the CCl4-induced cytotoxicity more strongly than 18 alpha-GL. Furthermore, the adsorbability of 18 alpha, beta-GA on primary cultured rat hepatocytes was higher than that of 18 alpha, beta-GL. These results suggest that 18 alpha, beta-GA is a more potent antihepatotoxic agent than 18 alpha, beta-GL, and that the potency of the antihepatotoxic compounds parallels their adsorbability in hepatocytes. PMID- 8202566 TI - Interactions of ginseng extract, ginseng separated fractions, and some triterpenoid saponins with glucose transporters in sheep erythrocytes. AB - The effects of Panax ginseng extract, ginseng saponins, and some other triterpenoid saponins on glucose uptake were examined by using sheep erythrocytes. Initial rates of glucose transport were determined by measurements of 2-deoxy-D-glucose (2-DG) uptake. From kinetic analysis apparent Km and Vmax values of facilitated glucose transport in sheep erythrocytes were calculated as 2.3 +/- 0.08 mM and 1.4 +/- 0.05 nmol/min/10(9) cells. The results showed that ginseng extract stimulated glucose uptake in sheep erythrocytes dose-dependently. Ginseng saponins, in general, also stimulated glucose transport. The maximum effect was observed at 1 microM of ginsenoside Rb1 showing an increase of 24 +/- 5% above basal activity. However, ginsenoside Rg3, chikusetsusaponin Ia, and glycyrrhetic acid induced significant inhibitory effects on glucose transport in sheep erythrocytes. PMID- 8202567 TI - Biologically active triterpene saponins from Bupleurum fruticosum. AB - Extracts of the root of B. fruticosum L. showed in a biological screening hemolytical activity, hepatoprotective and phagocytosis stimulating effects, and a specific inhibitory activity of leucine aminopeptidase. Further monitoring of the fraction with antihepatotoxic activity led to the isolation of an hepatoprotective saikosaponin identified as buddlejasaponin IV and the new malonylbuddlejasaponin IV, determined as saikogenin F-3-O-[6-O-malonyl-beta-D glucopyranosyl-(1-->2)-beta-D-glucopyranosyl (1-->3)]-beta-D-fucopyranoside. The structures were elucidated on the basis of the chemical and spectroscopic data. PMID- 8202568 TI - Effect of a peptide from Panax ginseng on the proliferation of baby hamster kidney-21 cells. AB - An alkaline fraction separated by ion exchange chromatographies from the water extract of Panax ginseng root stimulated the proliferation of baby hamster kidney 21 cells. Separation of the alkaline fraction by MCI-gel CHP 20P column chromatography followed by dialysis provided an active material. By a reversed phase HPLC the active material was separated into six fractions, and an active colorless compound 1 was obtained from fraction 2 in a pure state. Compound 1 was composed of the following amino acids; Gly, Arg, Glu, Val in a ratio of 1:1:1:1, and caused 20% enhancement of proliferation of BHK-21 cells at a concentration of 3.40 microM. On the basis of physical and spectral data the structure of compound 1 was established as a tetrapeptide, Gly-Arg-gamma-Glu-Val-NH2. PMID- 8202569 TI - Headspace constituents of opium. AB - The headspace of medicinal opium (Ph. Ned. 8) was analyzed by means of GC-FID, (+EI)-GC-MS (low and high resolution), and GC-FTIR. After olfactoric evaluation of the headspace sample by professional perfumers by the use of the GC-sniffing technique and after correlation tests with trained police dogs, more than 70 components were identified. With regard to the characteristic olfactoric properties of opium only one class of components, namely pyrazines, is of special interest. The synthetic mixture of 2-methyl-, 2,5-, and 2,6-dimethylpyrazine with 2-methoxy-3-isopropyl- and 2-methoxy-3-isobutylpyrazine was found to represent the original opium odour quite well. PMID- 8202570 TI - In vitro antifungal activity of essential oils against some isolates of Microsporum canis and Microsporum gypseum. PMID- 8202571 TI - Leishmanicidal activity of 2-benzoxazolinone from Acanthus illicifolius in vitro. PMID- 8202572 TI - Effect of ginsenoside Re on the electrophysiological activity of the heart. PMID- 8202573 TI - Pharmacological screening of plants recommended by folk medicine as snake venom antidotes; IV. Protection against jararaca venom by isolated constituents. AB - Fifteen compounds, isolated from plants reputed as snake venom antidotes, belonging to different classes of natural products, were shown to protect mice to a significant degree against the lethal action of the venom of Bothrops jararaca snakes. Administration was by the oral route, one hour prior to envenomation. The substances are nitrogen-free, low-molecular-weight compounds for which some kind of biodynamic activity has previously been reported. The fact that they are mostly trivial, naturally-occurring compounds should explain why plants used as snake-bite antidotes are so widely distributed over the plant kingdom. PMID- 8202574 TI - Is there universal recognition of emotion from facial expression? A review of the cross-cultural studies. AB - Emotions are universally recognized from facial expressions--or so it has been claimed. To support that claim, research has been carried out in various modern cultures and in cultures relatively isolated from Western influence. A review of the methods used in that research raises questions of its ecological, convergent, and internal validity. Forced-choice response format, within-subject design, preselected photographs of posed facial expressions, and other features of method are each problematic. When they are altered, less supportive or nonsupportive results occur. When they are combined, these method factors may help to shape the results. Facial expressions and emotion labels are probably associated, but the association may vary with culture and is loose enough to be consistent with various alternative accounts, 8 of which are discussed. PMID- 8202575 TI - Psychobiogenetics: adapted tools for the study of the coupling between behavioral and neuroendocrine traits of emotional reactivity. AB - The adaptive response to environmental challenges involves both behavioral and neuroendocrine adjustments. Several examples show that the behavioral and neuroendocrine responses to environmental stimulations, far from being independent, are frequently interrelated and/or coselected. The existence of such a coselection in genetically selected models provides an advantageous tool for the study of genetic influence on emotional reactivity and the mechanism of linkage between behavioral and neuroendocrine traits. In particular, the study of the Roman rat lines which have been selected for their performance in active avoidance behavior has allowed us to establish the respective role of genetic and maturation factors in the reactivity of these animals to stress. Indeed, the role of maturation in determining interindividual differences appears to be more marked in RLA than in RHA rats. The study of genetic factors, which play a major role in shaping individual characteristics of reactivity, may help, therefore, to elucidate the biological mechanisms coupling behavioral and neuroendocrine aspects of personality structure to emotional reactivity. PMID- 8202576 TI - Socioregulatory effects on squirrel monkey pituitary-adrenal activity: a longitudinal analysis of cortisol and ACTH. AB - Squirrel monkeys show unusually prolonged elevations in plasma cortisol when separated from like-sex social companions. To determine whether this hypersecretion of cortisol reflects a deficiency in feedback mechanisms that normally inhibit the prolonged activation of the pituitary-adrenal axis, we simultaneously measured plasma cortisol and corticotropin (ACTH) in 30 juvenile monkeys housed in established groups, individual cages, and newly formed groups. As found in recent longitudinal studies of adults, when juveniles were living without companions, mean cortisol titers were consistently higher than those observed when the same juveniles were living in like-sex social groups. When cortisol was elevated, however, ACTH titers were significantly and chronically reduced. These results suggest that elevated cortisol does inhibit ACTH synthesis or release, and that hypercortisolism in squirrel monkeys living without companions is not a consequence of chronic elevations in ACTH. Similar peculiarities in pituitary-adrenal activity are evident in a number of affective disorders in human beings. PMID- 8202577 TI - The relationship between the menstrual cycle and female sexual interest in women with PMS complaints and volunteers. AB - This study assesses the influence of menstrual cycle phases and hormones on female sexual interest in both a nonclinical sample of volunteers (n = 18) and women who complained of premenstrual tension (n = 150). Women were assessed prospectively for two menstrual cycles with daily symptom charts. In addition mental status was assessed clinically and the Moos Menstrual Distress Questionnaire completed in the follicular and premenstrual phases. On the basis of these assessments women were assigned to subject groups. During the second cycle, daily 24-h urinary estrogens and urinary pregnanediol were determined. Sexual interest and feelings of well-being were recorded on a daily symptom rating chart. Sexual interest was found to be significantly higher in the follicular and ovulatory phases, than in the luteal, premenstrual, or menstrual phases. Sexual interest and feelings of well-being were correlated (R = 0.29). Sexual interest and feelings of well-being were not correlated with urinary estrogen or pregnanediol levels. PMID- 8202578 TI - Independent segregation of a hyperactive hypothalamic-hypophyso-adrenal axis and a reduced behavioural reactivity in pigs. AB - When compared to European Large White, Chinese Meishan pigs have high levels of circulating ACTH and cortisol, and a reduced behavioural reactivity in various challenging situations such as exposure to a novel environment, two characteristic features of depression. We investigated whether this association is genetically built in or whether these psychobiological characteristics are fortuitously associated. Six-week-old piglets from the segregating F2 crosses between the Meishan and Large White breeds were studied in a standardised protocol of novel environment exposure. As expected from the genetic diversity, a wide range of variation was recorded for behavioural reactivity (locomotion, vocalisations). ACTH, cortisol, and glucose were measured in blood samples taken immediately before the test and at the end of the session. Again these measures varied considerably between animals, and the continuous distribution of the scores suggested that they are under control of numerous genes. Furthermore, no correlation could be found between neuroendocrine and behavioural measures. This result demonstrates that the association between high ACTH/corticosteroid levels and a low behavioural reactivity is not genetically controlled. PMID- 8202579 TI - Public health by accident. PMID- 8202580 TI - Who are the homeless? AB - To describe the demographic, social and medical morbidity and usage of health services of the population of single homeless individuals in Sheffield, a census was carried out over a 12-hour period at sites which homeless people frequent, as identified by those who work with the homeless. These sites included Salvation Army hostels, reception centres, probation day centres, voluntary organisation hostels, and cheap bed and breakfast accommodation. Data were collected by means of a self-administered questionnaire. A total of 340 single homeless individuals were studied, constituting 80-90% of the single homeless population of Sheffield, as estimated by field workers. The population was younger than those of earlier studies and contained a higher proportion of females (14%). One-fifth of the population had been homeless for less than six months, and 60% had been at their present lodging for less than six months. The population has a higher proportion of both ex-prisoners (49%) and ex-inmates of psychiatric hospitals (36%). Over a quarter admit to a history of alcoholism, and 9% to a history of drug abuse; 65% of the population are registered locally with a GP, and 53% of the population see their GP. Those who are more likely to use an Accident and Emergency Department are less socially integrated and more likely to be alcoholic. This study of the single homeless highlights a need for social change to reduce poverty, provide cheap available housing and provide support for disadvantaged groups. PMID- 8202581 TI - Children's safety in the home: parents' possession and perceptions of the importance of safety equipment. AB - A parental survey was administered by health visitors at the eight-month hearing test in five areas of Nottingham in order to examine possession and perceptions of the importance of safety equipment. The response rate was 82.2%. A sizeable proportion of families were found not to possess items of safety equipment thought to be appropriate for an eight-month-old child. Most items were perceived to be very important with a significant association between perceived importance and possession of equipment (P = 0.008). Perceptions of importance did not vary by socio-demographic variables but families on benefit, single-parent families, non-owner-occupiers and families with only one child possessed significantly fewer items. It is concluded that there is considerable scope for educating parents about safety equipment and that the provision of affordable safety equipment schemes should be considered by agencies implementing The Health of the Nation. PMID- 8202582 TI - Road traffic accidents in Saudi Arabia. AB - Road traffic accidents are a major health hazard in Saudi Arabia, particularly during Ramadan. The ensuing trauma has increased in direct proportion to the increase in the number of road vehicles. An audit of RTAs over a one-year period revealed that, out of 361 victims, 16% were under 10 years and 47% between 11 and 30 years. None of those involved in accidents was wearing a seat belt. Half of the children injured were pedestrians. There was a male to female ratio of 4:1 reflecting the driving laws in Saudi Arabia. Burst tyres due to intense heat were identified as a common cause (39%) of accidents. The introduction of seat belt legislation and stricter law enforcement should lead to a rapid reduction in morbidity and mortality on the roads in Saudi Arabia. PMID- 8202583 TI - Lanterns in the jungle: is the NHS driven by the wrong kind of efficiency? AB - The performance of the National Health Service is assessed in part by an Efficiency Index (EI) which is applied to the service as a whole as well as to individual health authorities. The EI relates increases in the amount of patient care activity to increases in total expenditure. The index can give a misleading impression of performance, creates perverse incentives and is at odds with the overall strategy of the health service which is to place greater emphasis on the promotion of health and to provide more care in primary and community-based settings. The philosophy, validity and appropriateness of the EI are discussed. PMID- 8202584 TI - Oral health knowledge, attitudes, behaviour and skills of children entering school in urban and rural areas in Tanzania. AB - This study analysed the prevailing oral health-related knowledge, attitudes and behaviour of children entering school in Tanzania. The assessment was conducted in a random sample of 200 children who were newly enrolled in first grade in urban and rural areas of the Ilala district, by means of interviews, oral hygiene check-ups and practical exercises. Toothbrushing was a prevalent habit among these children, but its efficiency was low. Modern toothbrushes were commonly used and preferred to wooden toothbrushes. Toothpaste was considered essential and commonly used in urban areas but, instead, charcoal or ash were used in rural areas. The children's sugar consumption was low, but they widely valued sugary snacks. They had low awareness of gum disease and tooth decay, and poor knowledge about the causes and prevention of these diseases. These findings indicate gaps in the children's oral health ideas and practices acquired from home. The ongoing school oral health education is a crucial opportunity for the required improvements. PMID- 8202585 TI - Hearing screening in Australian aboriginal university students. AB - Many indigenous peoples have been found to show an increased prevalence of both middle ear disorder and associated conductive hearing loss. Hearing loss may cause educational disadvantage during school years. For many indigenous populations in developed countries there are now increasing opportunities to participate in established formal education. This has led to greater numbers of indigenous students in post-secondary education. This study examined the results of a three-year hearing health programme for Australian Aboriginal students entering university studies. Prevalence rates were compared with those of urban Aboriginal adult non-students and non-indigenous populations. It was found that 15.5% of indigenous university students had a unilateral or bilateral hearing loss. Recommended screening procedures and methods to enhance classroom listening for indigenous hearing impaired students were suggested. PMID- 8202586 TI - The influence of dissemination of information on the changes of knowledge, attitude and acceptance of hepatitis B vaccination among hospital personnel in Chulalongkorn Hospital. AB - Lack of knowledge and negative attitudes were the main reasons for refusal, in a vaccination programme against hepatitis B using plasma-derived vaccine which was offered to the hospital personnel of Chulalongkorn University Hospital, Bangkok. Therefore, to ascertain whether an educational intervention among hospital personnel is effective in modifying acceptance of the vaccine, a quasi experimental design (using a before and after approach) was used to compare the knowledge, attitudes and acceptance rate of hepatitis B vaccination among 1,915 hospital personnel. After dissemination of information, knowledge and attitudes improved significantly, and acceptance rates were increased from 56.9% to 77.7% (P < 0.0000). More specific educational efforts should be started before launching vaccination programmes of this kind in order to increase acceptance. PMID- 8202587 TI - Factors associated with safe preparation and home use of sugar-salt solution. AB - The use of oral rehydration salts is frustratingly low, mostly because one must visit a health care provider to procure the packets. Mothers are advised to use sugar-salt solution (SSS) and other home-based fluids as first fluid replacement during diarrhoea. However, the use rate of SSS is also not encouraging and few mothers can prepare it correctly. We conducted an observation study on mothers who reported to the diarrhoea treatment centre of the International Centre for Diarrhoeal Disease Research, Bangladesh during September 1990 through to December 1992. At quarterly intervals, 240 mothers were recruited randomly to elicit their knowledge and ability to prepare SSS. Most (94.6%) of the mothers knew about the solution, but only 62% of them used the solution at home. The use rate was higher when mothers came to know about the solution through interpersonal communication (e.g. community health workers, doctors, friends, neighbours and relatives) and from multiple sources (72%) than when they learned about it from the media or from a single source (54%). As many as 85.4% of the mothers could prepare the solution within the safe limits of sodium concentrations (30 to 100 mmol/l). The figure rose to 95.8% after practical instruction as to how to prepare the solution. This improvement was dependent neither on the literacy level of mothers nor on their knowledge and use of the solution earlier. To increase interpersonal communication and to improve mothers' behaviour in using and correctly preparing SSS, every contact with health care providers should be utilised for organising sessions on the use and preparation of the solution. PMID- 8202588 TI - Prevalence and first-line treatment of diarrhoeal symptoms in the community. AB - By systematically sampling patient registers in two socio-economically contrasting Scottish urban general practices, 440 households were selected and contracted by a research health visitor who interviewed a household member in 425 of them (response rate = 97%). Information was obtained on the point and period prevalence of diarrhoeal symptoms in all household members (n = 1,335), and on the knowledge, attitudes and behaviour of the respondents. While the point prevalence was low (under 1% of the household members), around 12% were reported to have experienced symptoms in the three-month period prior to the interview, and these were associated with a small but far from negligible loss of time from school or work. There were no significant seasonal differences in prevalence rates, nor were there significant differences between the two practices. Knowledge about appropriate treatment was high, but there was some confusion about the administration of liquids (especially milk) other than water, and a high level of ignorance about the existence and purpose of oral rehydration solutions. These findings have implications for public education about the initial management of acute diarrhoeal symptoms. PMID- 8202589 TI - Evidence against the "oxygen-in-the-track" hypothesis as an explanation for the radiobiological low oxygen enhancement ratio at high linear energy transfer radiation. AB - Oxygen sensitizes cells toward the effect of ionizing radiation. This sensitization, quantified by the oxygen enhancement ratio (OER), decreases with increasing ionization density or linear energy transfer (LET) of the radiation applied. One explanation for the decreased OER at high LET offers the "oxygen-in the-track" hypothesis. It claims that oxygen is produced in the track of densely ionizing particles providing an oxic microenvironment around the relevant cellular target molecules, even if cells are exposed under anoxic atmospheric conditions. Experimental evidence is presented against this hypothesis. It is based on the different kinetic pattern of DNA double-strand-break rejoining observed in yeast cells exposed under oxic or anoxic conditions to 3.5 MeV alpha particles. PMID- 8202590 TI - Influence of DNA conformation on radiation-induced single-strand breaks. AB - It is usually assumed that sparsely ionizing radiation produces randomly distributed DNA breakages. This seems to be supported by the finding that in some DNA fragments single-strand scissions occur uniformly at all nucleotide sites, regardless of sequence. We performed experiments on two DNA fragments of about 300 bp having different conformation to test whether radiation-induced single strand breakage is dependent on DNA conformation. Breakage analysis was carried out by denaturing polyacrylamide gel electrophoresis, which allows determination of the broken site at single nucleotide resolution. We found uniform cutting patterns in B-form regions. On the contrary, X- or gamma-irradiation of curved fragments of kinetoplast DNA showed that the distribution of single-strand breaks was not uniform along the fragment, as the cleavage pattern was modulated in phase with the runs of A-T pairs. This modulation likely reflected the reduced accessibility of the sites which on hydroxyl-radical attack give rise to strand breaks. The cleavage pattern was phased with the runs of A-T pairs. Moreover, the overall yield of strand breaks was considerably lower in curved DNA fragments than in those with extended straight regions. The conformation effect found here indicates that the cleavage pattern reflects the fine structural features of DNA. PMID- 8202591 TI - Damage at two levels of DNA folding measured by fluorescent halo technique in X irradiated L5178Y-R and L5178Y-S cells. II. Repair. AB - In the preceding paper we described the properties of nucleoids analyzed with the fluorescent halo assay at pH 6.9 and 9, as well as in the presence of reducing and chelating agents and after X-irradiation. We found analogies between the properties of type I and II nucleoids, as examined by Lebkowski and Laemmli (1982), and nucleoids analyzed with the fluorescent halo assay. We concluded that radiation-inflicted damage at two levels of DNA folding is measured at pH 6.9 and 9. In this paper we examined repair of damage to the nucleoid structure as assayed by the fluorescent halo method in X-irradiated L5178Y (LY) sublines; R (radiation resistant, D0 = 1.4 Gy) and S (radiation sensitive, D0 = 0.5 Gy). Halo diameters were measured after cell lysis in the presence of propidium iodide (PI; 0.5 to 50 micrograms/ml) at pH 6.9 and 9. The ability of DNA to be rewound at 10 50 micrograms/ml of PI was impaired by X-irradiation and partly restored during 90-min post-irradiation incubation, indicating damage to the superhelical structure and its partial restoration. The exponential time constants for repair were 10.1 min (LY-S, 6 Gy), 11.2 min (LY-R, 12 Gy), and 20.3 min (LY-s, 12 Gy) when measured at pH 9. In X-irradiated (12 Gy) LY-S cells, slower restoration of DNA supercoiling was observed at pH9 than at pH 6.9. The presence of labile lesions at pH 9 did not prevent restoration of the higher-order DNA structure, as estimated from DNA rewinding at pH 6.9 in LY-S cells. PMID- 8202593 TI - The question of threshold doses for radiation damage: malformations induced by radiation exposure of unicellular or multicellular preimplantation stages of the mouse. AB - Mouse embryos of the one-cell stage or the 32- to 64-cell stage were exposed to various X-ray doses (one-cell stage: 0.25-2 Gy; 32- to 64-cell stage: 1-3 Gy). It turned out that the shape of the dose-response curves is statistically compatible with the assumption derived from biological considerations that there is no threshold for radiation-induced malformations in the case of the exposure of one cell embryos, whereas there is a threshold dose (close to 1 Gy) in the case of the exposure of 32- to 64-cell embryos. PMID- 8202595 TI - Estimation of dose rate for indoor radon from building materials. AB - The internal dose rate due to indoor radon (Rn) emissions from building materials is estimated. It is observed that the contribution from building materials to the dose rate is very small. The average indoor radon concentration in 75 different rooms is found to be 55 +/- 12 Bq. m-3. Assuming an occupancy factor of 0.8, the annual average effective dose equivalent is 1.7 mSv. It seems that soil gas is mainly responsible for the internal exposure from indoor Rn. PMID- 8202594 TI - Osteosarcomagenic doses of radium (224Ra) and infectious endogenous retroviruses enhance proliferation and osteogenic differentiation of skeletal tissue differentiating in vitro. AB - Cartilage tissue from embryonic mice which undergoes osteogenic differentiation during in vitro cultivation was used to study the effect of osteosarcomagenic doses of alpha-irradiation and bone-tumor-inducing retroviruses on proliferation and phenotypic differentiation of skeletal cells in a defined tissue culture model. Irradiated mandibular condyles showed dose-dependent enhancement of cell proliferation at day 7 of the culture and increased osteogenic differentiation at day 14. Maximal effects were found with 7.4 Bq/ml of 224Ra-labeled medium. Doses of 740 and 7400 Bq/ml of 224Ra-labeled medium induced increasing cell death. Retrovirus infection enhanced osteogenic differentiation and extended the viability of irradiated cells. After transplantation none of the treated tissues developed tumors in syngeneic mice. PMID- 8202596 TI - Workshop report: Techniques to Detect DNA Strand Breaks. Erlangen, Germany, 29-31 March 1993. PMID- 8202592 TI - Mechanisms of induction and repair of DNA double-strand breaks by ionizing radiation: some contradictions. AB - The various aspects of formation and repair of radiation-induced double-strand breaks (DSB) are summarized. Concerning the structure of DSB found in irradiated cells, enzymatic and microdosimetric analysis hints at complex damage of the DNA structure at the position of a DSB. With increasing LET, the DSB damage may be more complex than that induced by low-LET irradiation. Most of the DSB are repaired in the irradiated cell; apparently the kinetics of DSB repair and the fraction of unrejoined DSB determine cell survival or cell death. We do not know the details of the complex machinery of DSB repair; certainly recombination processes are involved, but there are still contradictions between our current knowledge about the mechanisms of recombinational DSB repair and the observed kinetics. PMID- 8202597 TI - Randomly distributed DNA double-strand breaks as measured by pulsed field gel electrophoresis: a series of explanatory calculations. AB - The aim of this article is to characterize expressions of relevance to the interpretation of pulsed field gel electrophoresis (PFGE) experiments where randomly distributed double-strand breaks (DSBs) are detected as smears of DNA fragments. Specifically, equations for conversion of percentages of fragments in defined size ranges to DSBs were derived. Several models have been used, one of which is based on theoretically fragmented DNA from the fission yeast Schizosaccharomyces pombe, which has three PFGE separable chromosomes. PMID- 8202598 TI - Gap junctional communication in excitable tissues; the heart as a paradigma. PMID- 8202599 TI - The prolamin storage proteins of wheat and related cereals. PMID- 8202600 TI - NMR studies of protein hydration. PMID- 8202601 TI - [Measure of bronchial hyperreactivity in epidemiology]. AB - First used to evaluate individuals with symptoms suggestive of asthma, the assessment of bronchial hyperresponsiveness is now commonly used in epidemiological studies, available methods being reproducible and portable. This chapter defines how to assess bronchial hyperresponsiveness in epidemiological studies, which factors need to be considered, what is the prevalence in different populations and finally what are the indications for measuring bronchial hyperresponsiveness in epidemiological studies. PMID- 8202602 TI - [Mechanisms of bronchial hyperreactivity: role of airway inflammation and atopy]. AB - The mechanisms of airway hyperresponsiveness are numerous and complex. The inflammatory process is one of the most important. It is characterized by epithelial damage and sloughing, by cellular infiltration of the bronchial mucosa and submucosa and by anatomical modifications of the bronchial wall. The cellular infiltrate is characterized by the presence of eosinophils, lymphocytes, monocytes-macrophages and mast cells. These cells are activated and release bronchoconstrictor and proinflammatory mediators. Eosinophils have toxic effects on the bronchial epithelium through the release of basic proteins, while lymphocytes play a central role through the release of cytokines, which can activate and recruit other cells. Mast cells have an important role of starter of the reaction but may also maintain it. Allergen inhalation in the laboratory, when a late response occurs, is responsible for an inflammatory reaction comprising eosinophil influx and activation and T lymphocyte activation. The intensity of the reaction is related to the transient increase in airway hyperresponsiveness confirming the important role of atopy and allergic reactions in airway hyperresponsiveness. However the same kind of inflammatory reaction can be present without atopy and antiinflammatory treatments, even if they reduce airway hyperresponsiveness, may not completely abolish it. This emphasises the complex mechanisms involved in persistent airway hyperresponsiveness. PMID- 8202603 TI - [Is there a genetic component in bronchial hyperreactivity in the human species?]. AB - Whether a hereditary, genetic component of human non allergenic bronchial hyperresponsiveness exists in man is controversial. Therefore, the "Dutch hypothesis" that bronchial hyperresponsiveness is a risk factor of asthma and chronic bronchitis has not been validated by hard data, although it was put forward more than two decades ago. In some inbred strains of mice and rats, bronchial hyperresponsiveness to acetylcholine or serotonin is transmitted as a Mendelian monogenic trait or a polygenic one. Genetic studies of human bronchial hyperresponsiveness are difficult, if only because it is an ill-defined phenotype, and because acquired, inflammation-related bronchial hyperresponsiveness is at the forefront in airway diseases such as asthma. Studies of concordance in mono- and dizygotic twins, of distribution in the general population, and of familial inheritance suggest transmission from generation to generation of human bronchial hyperresponsiveness. This only applies to bronchial response to cholinergic agents because of the small number of studies done with other bronchial challenges. Furthermore, there is no agreement on the mode of transmission of this specific type of bronchial hyperresponsiveness. One hopes that combining genetic epidemiology with molecular genetics in the forthcoming years will result in a better understanding of genetic risk factors of human bronchial hyperresponsiveness. PMID- 8202604 TI - [Bronchial hyperreactivity: neurogenic factors]. AB - Over the last fifty years, the role of neurogenic factors in asthma and bronchial hyperreactivity has been intensively investigated. The roles of the cholinergic and adrenergic nervous systems have been clarified and several sub-types of muscarinic receptors identified. The localisation and functions of both muscarinic and adrenergic receptors have been further specified. It has also been shown that afferent nerve fibers as well as sympathetic and parasympathetic nerve fibers secrete various neuropeptides. The physiological role of these peptides is not yet known but it appears that they have a powerful effect on bronchial smooth muscle tone, microvascular permeability, mucus secretion and secretion of mediators by inflammatory cells. The results of numerous studies suggest that there are several abnormalities in the adrenergic and cholinergic nervous systems of asthmatic patients, but that these abnormalities are not themselves the cause of bronchial hyperreactivity. They may however contribute to enhance it. The role of the various newly identified neuropeptides in the genesis and maintenance of bronchial hyperreactivity remains to be determined. PMID- 8202605 TI - [Mechanisms of bronchial hyperreactivity. Role of smooth muscle]. AB - The understanding of the cellular and molecular mechanisms involved in the contraction of airway smooth muscle has tremendously advanced in the recent years. Extracellular messengers that control the muscle contraction as well as both the membrane transduction processes and the activation of the contractile proteins are known in some details. Sensitization alters the contractility of airway smooth muscle. It increases shortening in the early phase of the contraction when rapidly cycling cross bridges are operative. At the molecular level, the responsible mechanism is an increment in the activity of the processes leading to phosphorylation of the myosin light chain. Such an alteration in the airway smooth muscle contractility may be observed in the early phase of the development of bronchial hyperresponsiveness. PMID- 8202606 TI - [Mechanisms of bronchial hyperreactivity. Bronchial edema, mechanical and vascular factors]. AB - Hindrance to gas flow in the bronchi is affected not only by airway smooth muscle tone but also by airway circulation. Congestion and oedema increase airway wall thickness and act in series with airway smooth muscle contraction to reduce airway calibre, an effect which is more marked in small and intermediate bronchi. Many mediators, neuromediators, paracrine mediators produced by resident (epithelium) or migrant (inflammatory cells) cells share bronchomotor and vascular effects. In addition, contraction of airway smooth muscle and vascular phenomena are mechanically coupled. Contraction of airway smooth muscle facilitates vascular congestion and oedema because the diameter of the muscle ring is more reduced than the external diameter of the airways. In addition, a negative intrathoracic pressure, e.g. in asthma, increases the mechanical loading of both ventricles, thereby facilitating pulmonary and bronchial oedema. The effects of this mechanical coupling are enhanced by airway inflammation that facilitates both vascular congestion and leakage. Stimuli such as exercise and hyperventilation cause airway vasodilatation which, in turn, facilitates and, possibly, triggers the post-exercise asthma attack. Conversely, congestion and vasodilatation may have a protective effect through an increase in the clearance of bronchoconstrictor substances, or in reducing the amplitude of airway cooling and water loss in exercise-induced asthma. The relative role in bronchial hyperresponsiveness of airway smooth muscle contraction and vascular phenomena probably depends upon individual factors such as, for instance, both intensity and nature of inflammation of the airway walls. PMID- 8202608 TI - [Bronchial hyperreactivity other than that seen in asthma]. AB - Although generally associated with asthma, bronchial hyper-responsiveness has been observed in several clinical situations. Indeed, it has been clearly shown that patients with allergic rhinitis exhibit frequently bronchial hyperresponsiveness. The latter may be an important factor in the development of chronic airway obstruction. Airway hyperresponsiveness to direct bronchoconstrictors, histamine and metacholine, is seen also in subjects with chronic airflow limitation. Several lines of reasoning suggest that this may be different than the airway hyperresponsiveness seen in asthmatics and may predominantly relate to the degree of airflow obstruction. Consequently, in the presence of resting airflow obstruction, histamine and metacholine tests are difficult to interpret vis-a-vis a diagnosis of asthma. Some studies suggest accelerated decline of lung function in subjects with chronic airflow limitation and airway hyperresponsiveness. In interstitial lung disease preliminary data form subjects with lung diseases localized to the pulmonary interstitium suggest no (or very little) tendency to airway hyperresponsiveness. However, more data are necessary. Subjects with bilateral lung transplantation appear to develop mild, generally asymptomatic airway hyperresponsiveness which has been suggested to be due to cholinergic denervation hyper-sensitivity. Finally, asthmatics and nonasthmatics both may develop increased degrees of airway responsiveness following viral respiratory tract infections. Virus-induced airway inflammation is likely important in the pathogenesis of asthma in some subjects. PMID- 8202607 TI - [Non-allergenic bronchial hyperreactivity. Measurement methods and reproducibility]. AB - Different methods are available to measure non-allergic airway responsiveness. In the last years, efforts have been made to improve standardization of these methods, in order to allow comparison of data from different sources. The most currently used bronchial provocation tests are those with nebulisation of histamine or methacholine either a tidal volume or from a dosimeter, a dose response curve being obtained in measuring expiratory flows or airway resistance. Inhalation of non-iso-osmolar solutions, cold air hyperventilation, exercise or other agents and stimuli may be used to estimate airway response, but they are more useful as a research tool than for clinical purposes. The reproducibility of bronchial provocation tests is dependent of different factors such as those related to the subject (asthma stability, performance of tests, medications, circadian variations), technical factors (type and calibration of the apparatus, nebulizer output, measurements, solutions) and to the methods of calculation of the bronchial response. Short-term reproducibility of the different types of bronchial provocation tests is usually good although long-term stability needs to be further assessed. A correlation has been reported between the response to most of the different bronchoconstrictor agents, although variable. PMID- 8202609 TI - [Non-allergenic bronchial hyperreactivity and occupational agents]. AB - The relationship between occupational asthma (OA) and non-specific bronchial responsiveness (NSBR) is reviewed. Natural or laboratory exposure to ubiquitous allergens can induce or increase NSBR. Reduction of exposure has an opposite effect. Preliminary results suggest that NSBR is not a predisposing factor to OA. NSBR assessment can be useful in screening for OA, before employment to document baseline levels and serially afterwards, alone or combined to immediate skin reactivity to the occupational agent, to document the onset of OA. Showing NSBR is essential to the diagnosis of OA. Although specific broncho-provocation tests in a hospital laboratory still represent the gold standard to confirm OA, the demonstration of changes in peak expiratory flow rates, in particular if such changes are coupled to NSBR, is an important diagnostic tool. NSBR assessment is also an interesting guide to specific bronchoprovocation in the laboratory. Several studies have documented a reduction in NSBR in some cases of OA after removal from exposure to the causal agent. The degree of NSBR is one of the criteria that have been suggested in setting permanent disability in subjects with OA. Increased NSBR can exist in other occupational conditions and represents an essential feature of Reactive Airways Dysfunction Syndrome (RADS). PMID- 8202610 TI - [Is non-allergenic bronchial hyperreactivity a good diagnostic test for asthma?]. AB - The measurement of non-allergic bronchial hyperreactivity brings limited information in the diagnosis of asthma, whether for epidemiological purposes or for an individual patient. Its sensitivity and specificity in the general population amount to 46 and 89% respectively. It follows that the positive and negative predictive values are of little use when the prevalence of asthma lies between 1 and 10%. The situation is different, more complex, but not necessarily more favorable when one deals with one given patient. The characteristics of the test may vary as a function of the severity of the disease (concept of spectrum bias). Furthermore, the differential diagnosis will be made for other diseases that can also be associated with bronchial hyperreactivity. The negative and positive predictive values of this test will therefore be sufficiently informative only when the diagnosis is already certain. PMID- 8202611 TI - [Role of non-allergenic bronchial hyperreactivity follow-up studies in the assessment of prognosis of asthma]. AB - Asthma is affected by increasing mortality and morbidity as well as by increasing costs due to hospitalizations and visits to the emergency room. It is mandatory to propose an accurate follow-up of asthmatic subjects so that they can live a normal life and avoid hospitalizations. Two tools can be used: 1) notification in a diary of daily symptoms; 2) serial assessment of peak expiratory flow rates and FEV1. These methods are widely suggested and interesting. However, several aspects including the compliance of asthmatic subjects with the assessment, remained to be examined. According to cross-sectional studies, serial measurement of non-allergic bronchial responsiveness is significantly related to the clinical and functional severity of asthma. Nevertheless, longitudinal studies do not show a satisfactory correlation. The reason for these discrepancies is unknown. Although other studies are needed to obtain direct information on the severity of bronchial inflammation, the current state of knowledge does not suggest that serial assessment of bronchial responsiveness is sufficiently valid to introduce its routine use in the follow-up of asthmatic subjects. PMID- 8202612 TI - [Bronchial hyperreactivity in 1994, a cheerful quinquagenarian. Conclusions]. AB - A review is made of the principal themes that are discussed in this supplement of the Revue des Maladies Respiratoires. Three important questions on bronchial hyperresponsiveness, a key feature of asthma, are raised: 1) the clinical usefulness of its assessment, mostly in the atypical forms of asthma and in occupational asthma and, less so, to estimate the severity of asthma; data derived from the Bayesian analysis lead to the conclusion that it is a test which is better for excluding rather than for confirming asthma; in an epidemiological setting, the assessment of bronchial responsiveness should be carried out to assess both host factors and the effect of environmental exposure; 2) the method of assessment which should take into account the stimulus, be it pharmacological or not, the physiological index used to assess the response and the mode of expression of results; 3) finally, the mechanisms of bronchial responsiveness are probably multiple as examined in different chapters of this supplement. PMID- 8202614 TI - 'Salami' publishing: when is enough enough? PMID- 8202613 TI - [Bronchial hyperreactivity. Definitions and history]. AB - The various definitions that are proposed for bronchial hyper-responsiveness (BH) are discussed. The semantic problems related to these definitions are presented: 1) the translation of bronchial hyperresponsiveness into French can vary; 2) BH is not synonymous of abnormal contraction of airway smooth muscle; 3) there is also some confusion of BH with the clinical status of asthma, which is excessive. The authors also review the difficulties related to the purely operational character of the definition itself: 1) BH has a continuous distribution in a general population; 2) BH can be expressed by various indices; 3) stimuli to reveal BH are various; 4) there are various types of BH related to the causal conditions; 5) there are different sites of BH within the airways. The authors also review the historical background of BH with some emphasis on the contribution of French-speaking research workers. PMID- 8202615 TI - Using algorithms in rehabilitation nursing: an educational strategy. AB - The purpose of this article is to describe the use of algorithms in the specialty practice of rehabilitation nursing. Algorithms are particularly useful for the nurse who is new to rehabilitation because they can offer guidance in some important aspects of clinical decision making. In this article, the authors include information on the historical uses of algorithms, the benefits of using algorithms, and the ways in which algorithms are developed. Examples are also included, and suggestions for further development of algorithms in rehabilitation nursing are proposed. PMID- 8202616 TI - A nursing management protocol for incontinence. AB - Urinary incontinence affects people of all ages, but it is more prevalent in the elderly. Unrecognized, this problem can lead to infections, falls, and emotional distress. Health care professionals can play a vital role in the prevention and treatment of incontinence by simple techniques such as habit training and prompting. This article describes three case studies of elderly male clients with incontinence and discusses the implementation and outcome of a nursing management protocol with the clients. PMID- 8202617 TI - Analysis of the roles and responsibilities of rehabilitation nursing staff. AB - This article describes a study whose purpose was to identify the roles and the responsibilities of rehabilitation nursing staff members, specifically the registered nurses and the nurse extenders, or rehabilitation technicians. The members of the nursing staff kept work diaries, listing each work activity and the time spent on that activity. Results of the study indicated that the majority of the registered nurses' time was focused on either direct or indirect patient care. The majority of the rehabilitation technicians' time was focused on direct patient care; however, rehabilitation technicians on the evening shifts spent significantly more time in indirect patient care and unit maintenance than did their day-shift counterparts. Data analysis indicated that 33% of evening-shift rehabilitation technicians' time and 36% of day-shift rehabilitation technicians' time was unaccounted for in the work diaries. As a result of this study, the authors recommend a review of the job description for rehabilitation technicians. Furthermore, the results identify a need for staff development education for rehabilitation technicians so that they can expand their roles and responsibilities. PMID- 8202618 TI - Developing a paper presentation. AB - The purpose of this article is to provide suggestions for developing and presenting papers at an educational conference or other professional meeting. The authors offer suggestions on how to write an abstract, deal with rejection or success, develop an outline, construct a lecture, select audiovisual materials, and use public-speaking skills. The practical strategies described in this article are intended to enable rehabilitation nurses and other readers to develop and/or enhance their paper presentations. PMID- 8202619 TI - A rehabilitation nursing orientation program. AB - At Carondelet St. Mary's Hospital and Health Center in Tucson, AZ, a comprehensive orientation program for rehabilitation nursing in conjunction with a preceptor-guided orientation process was developed. This orientation program has provided a base of knowledge for entry-level staff and is an important source of review and reference for experienced rehabilitation nurses. PMID- 8202620 TI - 'Professional rehabilitation nursing': an elective course for nursing students. AB - An elective course, "Professional Rehabilitation Nursing," was developed at the University of Louisville School of Nursing to examine the scope of professional nursing practice in selected cardiac, neurologic, and pulmonary rehabilitation settings. In this elective, rehabilitation professionals presented content in their respective areas of expertise. Course methods focused on group discussions and client contact in rehabilitation settings. Students praised the course as informative and enjoyable. PMID- 8202621 TI - Using nursing diagnoses and interventions in an inpatient amputee program. AB - The purpose of this study was to provide a descriptive analysis of an inpatient amputee program at Spaulding Rehabilitation Hospital (SRH) in Boston; the analysis focused on nursing diagnoses and interventions documented in the medical record. The study was based on a retrospective chart review conducted for 96 inpatient lower-extremity amputees who were admitted from October 1988 through September 1989. The results of the study identified common nursing diagnoses and interventions used for a medically complex population of people who had had amputations. In addition, the study showed that most subjects improved in functional status, thus confirming the success of the program. All subjects were either discharged to their homes or transferred to an acute care facility. The study results will be used to develop a standardized nursing care plan, as well as creative new modalities for patient and family education, at SRH. PMID- 8202622 TI - Heterotopic ossification: a review of symptoms and treatment. AB - Heterotopic ossification (HO) is the abnormal development of bone tissue within soft tissue. Its etiology and pathology are uncertain. This condition is often seen near one or more joints in people who have sustained traumatic injuries of varying types. Symptoms include localized swelling, pain, increase in temperature, and loss of the joint's range of motion at the affected site. Further testing generally reveals an increase in serum alkaline phosphatase, a positive three-phase bone scan, and the identification of bone formation on radiographs. A review of the literature reveals that common treatment options include range-of-motion exercises to maintain joint function, pharmacologic intervention, possible irradiation of the site, and surgical removal of ankylosing bone. The rehabilitation nurse must be aware of this medical complication to participate in its identification and treatment, as well as to be effective in counseling and educating patients and their families. PMID- 8202623 TI - Lydia E. Hall: rehabilitation nursing pioneer in the ANA Hall of Fame. PMID- 8202624 TI - Advancing certification in rehabilitation nursing. PMID- 8202625 TI - Differentiation of neoplastic cells toward normal induced by vitamin D3 derivatives. AB - Two new analogs of 1,25 dihydroxy vitamin D3 (calcitriol, DHCC), the active metabolite of vitamin D3 (cholecalciferol (D3) are less active on calcium metabolism and less toxic than (DHCC). They had increased differentiation inducing activity towards normal on human myeloblastic leukemia cell line HL-60 and on histiocytic lymphoma cell line U-937 consisting of monoblastoid cells. 1,2 tetradeconyl phorbol 1, 3 acetate (TPA) was used as a positive control in these experiments. PMID- 8202626 TI - Effects of dietary vitamin D deficiency on the cardiovascular system. AB - Experiments were performed on normotensive rats exposed to vitamin D deficient and control diets from the 22nd to the 180th day of age. In 60-120- and 180-day old rats. The following parameters were evaluated: a) The vasomotor responses elicited by receptor agonists in the absence and in the presence of the respective antagonists [L-norepinephrine (NE) before and 5 min after prazosin; L isoprenaline (I) before and 5 min after DL-propranolol; L-dopamine (DA) before and 5 min after L-sulpiride or SCH 23390 or chlorpromazine; acetylcholine (Ach) before and 5 min after atropine; histamine (H) before and after chlorpheniramine; 5-hydroxytryptamine (5-HT) before and 5 min after methysergide or ketanserin]; by carotid-sinus baroreceptor stimulation (CO) before and 5 min after hexamethonium, and by electrical stimulation of the vagus peripheral head (V) before and after atropine; b) Reflex tachycardia elicited by bilateral carotid occlusion (CO) (for 40 sec) and by sodium nitroprusside; c) Catecholamine (norepinephrine, epinephrine) and arginine-vasopressin plasma levels; d) Cholesterol, triglyceride and electrolyte (Na+, K+, Cl-, Ca2+) serum levels. Our results showed that vitamin D deficient diets induced a decrease in pressor responses to NE and CO, and an increase in hypotensive responses to I, DA, Ach, H, 5-HT and V. Changes of arterial blood pressure, heart rate, catecholamine and arginine-vasopressin plasma levels were not observed. Cholesterol, triglyceride and electrolyte (Na+, K+, Cl-) serum levels were not modified, while Ca2+ serum levels decreased. In conclusion, our data suggest that vitamin D depletion can induce changes of pressor and depressor vasomotor responses and suppose a direct role for vitamin D in regulating vasomotor reactivity. PMID- 8202627 TI - Inhibition of IL-6 and IL-8 production in human fibroblast cell lines by 1,25 (OH)2 vitamin D3 and two of its analogs with lower calcemic activity. AB - In human fibroblast cultures TPA increased IL-6 and IL-8 production. This was reduced by vitamin D3 metabolites and analogs. The two analogs employed: 1,25 (OH)2-22 (E)-dehydro-24-monohomo vitamin D3 (Compound A) and 1,25 (OH)2 -22 (E) dehydro-24 dihomo-vitamin D3 (Compound B) may be useful in the therapy of pathologic proliferative disorders including psoriasis, particularly since they are less toxic and have less effect on calcium metabolism than vitamin D3. PMID- 8202628 TI - Relationship between cytokines and leukotriene B4 in sepsis. AB - To clarify the relationship between cytokines and arachidonic acid metabolites, we measured tumor necrosis factor (TNF-alpha), interleukin 8 (IL-8), and leukotriene B4 (LTB4). The subjects consisted of 30 patients with sepsis. The results were compared between patients who died (Group A) and those who survived (Group B). All TNF-alpha, IL-8, and LTB4 levels were significantly higher in Group A than in Group B, reflecting the severity of the disease. The LTB4 levels were significantly correlated with the TNF-alpha level and the IL-8 level. These results suggest that inflammatory cytokines, excessively produced due to inflammatory reactions, stimulate as a mediator the release of arachidonic acid, increasing LTB4 production. PMID- 8202629 TI - Correlation between bleeding time and antithrombotic effect of platelet suppressive agents in rat experimental model. AB - To examine whether the dosage of a platelet-suppressive agent at which an antithrombotic effect is adequate and bleeding tendency is not increased can be found, the antithrombotic effects, antiplatelet effects and bleeding times of ticlopidine and aspirin were investigated in the rat experimental thrombus formation model. Thrombus formation was determined by measuring the change in wet weight of a silk thread placed in a carotid arteriovenous shunt. Ticlopidine inhibited thrombus formation and platelet aggregation at rather low doses (50-100 mg/kg) without prolonging bleeding time. However, aspirin did not inhibit thrombus formation at even the highest examined dose (200 mg/kg), while bleeding time was prolonged at even the lowest dose (50 mg/kg). These results suggest that a dosage of antithrombotic agent that does not increase bleeding tendency can be easily established using ticlopidine, although it is relatively difficult using aspirin. PMID- 8202630 TI - Alteration of renal receptors for atrial natriuretic peptide and vasopressin in spontaneously hypertensive rats treated with antihypertensive diuretics. AB - To investigate the alteration of the renal atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) receptors in the controlled hypertensive state of spontaneously hypertensive rat (SHR) treated with antihypertensive diuretics, 12 weeks old SHRs were administered an antihypertensive diuretic, furosemide, trichloromethiazide, or indapamide, daily for 10 days and investigated by radiolabeled receptor assay (RRA) of ANP and AVP. The urine volume was significantly increased in all groups treated with antihypertensive diuretics as compared with the untreated control group on day 3. Systolic blood pressure was significantly decreased in groups treated with both trichloromethiazide and indapamide. The number of renal ANP receptors decreased; affinity was increased only in the SHR administered indapamide. The affinity of the renal AVP receptor was also decreased in that group. Alteration of ANP and AVP receptors was observed only in the group treated with indapamide. This indicates that the ANP and AVP receptor in the kidney of SHR was changed not only by diuresis or reduction of blood pressure, but by the pharmacological action of indapamide. PMID- 8202631 TI - Effects of glycosaminoglycan polysulfate on extracellular matrix metabolism in human skin cells. AB - The effects of chondroitin polysulfate (CPS), a semi-synthetic oversulfated chondroitin sulfate, on the metabolism of extracellular matrix in human skin cells were examined. CPS accelerated the production of glycosaminoglycans (GAGs) in human dermal fibroblasts in a dose dependent manner (0.1-3.0 micrograms/ml), but did not modulate the production of noncollagenous protein and collagen, or [3H]-thymidine incorporation into DNA. However, higher concentrations (> 10 micrograms/ml) of CPS suppressed the [3H]-thymidine uptake by fibroblasts. More than 80% of total synthesized GAGs were found to be hyaluronate, whereas CPS did not alter their composition. These results indicated that CPS preferentially enhances the production of GAGs in human dermal fibroblasts, and that GAGs and DNA synthesis in the fibroblasts are independently regulated. Furthermore, CPS might be a unique material able to maintain the level of GAGs in the human skin. PMID- 8202632 TI - Glucocorticoid induction of hepatic acetyl CoA:arylamine N-acetyltransferase activity in the rat. AB - N-Acetylation, which is catalyzed by the enzymes N-acetyltransferase (NAT), is an important biotransformation pathway for the elimination of a wide variety of xenobiotics. Based on reports by several investigators that hydrocortisone (HYD) pretreatment increases N-acetylation in the rabbit, we examined the potential of glucocorticoids to induce NAT in the rat. Rats received pretreatment with relatively equipotent doses of HYD, prednisolone (PRED) or dexamethasone (DEX) for 5 or 10 days. Livers were removed 24 hr after the last dose and NAT activity was determined by measuring the formation of N-acetylprocainamide in cytosolic incubations in the presence of 0.42 mM acetyl CoA. All three glucocorticoids were found to cause a modest induction of NAT activity towards procainamide after dosing for 10 days. When normalized to cytosolic protein content, the potency of induction was PRED > DEX > HYD (30, 29 and 18% increase, respectively), while normalization to liver weight demonstrated equipotent NAT induction by the three agents (40%). These data indicate that glucocorticoids are capable of producing a modest induction of NAT activity in the rat. PMID- 8202633 TI - Clinical effects of intramuscular administration of a small dose of polymyxin B to patients with endotoxemia. AB - The effects of intramuscular injections of minute amounts of polymyxin B were studied in 42 patients with endotoxemia. Plasma endotoxin was measured by means of an endotoxin-specific Endospecy test (Seikagaku Corp., Tokyo, Japan) after pretreatment of the plasma with a new perchloric acid method that we developed. The normal value of plasma endotoxin is less than 9.8 pg/mL. Polymyxin B was administered at a dose of 12,500 U every 6 hours. Plasma endotoxin rapidly decreased to the normal range in 40 of the 42 patients. Body temperature fell significantly. APACHE II scores were also significantly improved. Tumor necrosis factor-alpha and interleukin-6 (IL-6) decreased in survivors, while tending to persist in high values in patients who died. No side effects were observed in any of the patients. In conclusion, intramuscular injections of small doses of polymyxin B were useful in the treatment of endotoxemia. PMID- 8202634 TI - Correlation between various ratios of serum thyroid hormones and liver cytochrome P-450 in CCl4-treated and untreated rats. AB - In a search for clinically useful indices of liver microsomal function, the correlation between various ratios of serum thyroid hormones, triiodothyronine (T3) and reverse T3 (rT3), and liver microsomal P-450 was investigated in CCl4 treated and untreated rats. Serum and liver samples were obtained before (untreated group, n = 15) and 4 hr after CCl4 administrations (0.2 ml/kg, s.c.). The CCl4-treated group (n = 11) included five randomly chosen untreated rats. In both groups, the ratios of T3/rT3, rT3/T3, and T3/T3+rT3 correlated significantly with liver cytochrome P-450 levels. From these results, it is suggested that the ratios of T3/T3+rT3, T3/rT3, and rT3/T3 can be used as the indices of liver microsomal P-450 levels and that thyroid hormone metabolism is related to liver cytochrome P-450, as was evidenced in untreated animals. PMID- 8202635 TI - Are tryptase and cathepsin D related to Helicobacter pylori infection and mucosal gastrin in peptic ulcer? AB - The pathogenesis of peptic ulcer is a complex phenomenon and several factors are thought to be involved in this process. Among others, Helicobacter pylori infection, hypergastrinaemia and some proteases seem to play an essential role in inducing peptic ulceration. We investigated whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (a lysosomal hydrolase which seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked to Helicobacter pylori infection and mucosal content of gastrin. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer and 11 with duodenitis. Tryptase and cathepsin D were measured in mucosal biopsy specimens (body and antrum of the stomach and duodenum) using IRMA methods. Gastrin was assayed in the antral mucosa by means of a RIA method. Helicobacter pylori infection was histologically evaluated (Giemsa). Tryptase and cathepsin D levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. The mucosal content of cathepsin D, but not that of tryptase, was associated with Helicobacter pylori infection. Tryptase, on the other hand, was related to gastrin content. No correlation was found between the two enzymes. It is concluded that tryptase and cathepsin D probably reflect different pathophysiological modifications in ulcer disease. Cathepsin D seems to be mainly related to the phlogistic reaction of the mucosa to Helicobacter pylori infection; tryptase may reflect and indirect link between the action of gastrin and the function of mast cells. PMID- 8202636 TI - Development of an experimental model of an acute respiratory failure by intratracheal sea water infusion: a comparison with a conventional oleic acid induction. AB - An experimental model of acute respiratory failure (ARF) was successfully developed in dogs by endotracheal sea water infusion. Serial changes in blood gases and hemodynamics, and histological changes in the lungs after use of this method were compared with those of the conventional model induced by oleic acid, and the following results were observed. Blood gases deteriorated more rapidly after sea water than after oleic acid, while the changes caused by oleic acid progressed with time, and those caused by sea water did not. Not only systemic but also pulmonary hemodynamics were adversely influenced by oleic acid, but not by sea water. Extravascular lung water was observed to increase significantly in both groups. The increase was linear after oleic acid treatment, however, while with the sea water method it leveled off to a plateau. There was no significant difference between the histological changes in lungs of the two models. Our model will provide many advantages over the conventional one using oleic acid, and will be useful for studying the pathophysiology of ARF and its therapeutic strategies, such as extracorporeal membrane oxygenation and/or carbon dioxide removal. PMID- 8202637 TI - Application of the image analysis system and Imago program to biological samples. AB - Recent developments in computer systems and new stereological tools have made estimation of quantitative data in biological material simple, easy and fast. The purpose of the present study is to show the advantages and disadvantages of a new program developed by the University of Cordoba for the determination of stereological measurements. As an example, endometrial material was used for demonstrating the technical characteristics. Thus, the nuclear area and volume weighted mean nuclear volume-Vv(nucl)-of 30 routinely processed, paraffin embedded endometrial specimens from 12 atypical hyperplasias (AH) and 18 well differentiated adenocarcinomas (WDA) were investigated. We show the excellent visualization of the material and rapid measurement of these quantitative parameters using the Imago program. In addition, the mean values of Vv(nucl) are more efficient and useful in separating AH and WDA than the mean nuclear area. It is concluded that Vv(nucl) is a superior and sensitive estimator for discrimination. PMID- 8202638 TI - Effect of cyclosporin treatment on metabolic and hormonal responses to mixed meal plus oral glucose in dogs with intrasplenic pancreatic islet autograft. AB - We evaluated the effect of immunosuppressive concentrations of cyclosporin A (CsA), given intramuscularly, on the levels of glucose, insulin, C-peptide, glucagon, pancreatic polypeptide (PP), lactate, alanine and beta-hydroxy-butyrate in a group of pancreatectomized mongrel dogs with intrasplenic islet autografts, given mixed meal and oral glucose, while on or off CsA therapy. In whole blood, HPLC-measured drug levels ranged from 412 to 803 ng/ml. Basal glucose and insulin concentrations did not differ significantly between non-pancreatectomized, control dogs and transplanted animals, whether on or off CsA. After the meal challenge, glucose levels were significantly higher in transplanted animals than in normal dogs, and no additional deleterious effect of CsA was observed. Similar insulin and C-peptide responses were found in animals either on or off CsA treatment. Fasting and post-meal concentrations of glucagon, PP and intermediate metabolites were not affected by the drug. These results suggest that intramuscular CsA, given at doses known to sustain islet allograft function, has no detrimental effect on the hormonal and metabolic responses to mixed meal and oral glucose in dogs with intrasplenic islet autografts. PMID- 8202639 TI - Experimental model of liver metastases: adhesion and growth of cells on contact with endothelial or hepatocyte cell monolayer cultures. AB - In a rat colon carcinoma model (DHD/K 12-PROb), two varieties of cells were selected after in vivo passaging: PROb h2, representing a liver-specific variant and PROb Mp1, representing a lung metastatic variant and producing liver and lung metastases after intracecal injection (one out of four). The study of the adhesion and the growth of cells in vitro for contact hepatocytes and/or endothelial cells gave the following results: (1) except for PROb Mp1, tumor cell growth was independent of the cell support; (2) adhesion of PROb Mp1 to endothelial cells was lower between 30 and 120 min, whereas adhesion of PROb h2 to hepatocytes was greater and durable after 60 min (P < or = 0.05). These results suggest that the formation of liver metastases in a dynamic process and that tumor cells have a great ability to adhere to hepatocytes. Improved by serial passaging in vivo, our intracecal model might be useful for studying many aspects of the pathogenesis of colon cancer metastasis, while concurrent in vitro studies of the adhesion and growth ability of cells might be a useful indicator for assessing the in vivo behavior. PMID- 8202640 TI - A single intravenous high dose of cholic acid to a pregnant ewe does not affect fetal well-being. AB - Cardiovascular variables of both mother and fetus and total bile acid levels were monitored in amniotic fluid and in maternal and fetal plasma after the administration of a single intravenous high dose (29 mg) of cholic acid to a pregnant ewe. We observed the diffusion of significant quantities of cholic acids from the mother to the fetus and amniotic fluid. Nevertheless, cardiovascular parameters (heart rate, blood pressure, PO2, PCO2 and pH) were not affected, neither did intra-amniotic pressure show significant changes compared with the initial experimental conditions. It is concluded that an acute increase in maternal plasma levels of bile acids does not produce important adverse effects in either the mother animal or the fetus and consequently, if bile acids should be deemed responsible for any deleterious effect observed in a preterm fetus in intrahepatic cholestasis, this should be considered as the consequence of a chronic process. PMID- 8202641 TI - Determination of endothelin-1 immunoreactivity in plasma, cerebrospinal fluid and urine. AB - Endothelin-1 (ET-1) is a potent vasoconstrictor peptide apparently involved in a number of vascular diseases in man. Nonetheless, its determination in biological samples is difficult, and data on plasma or urine concentrations are controversial. We investigated different sample preparation procedures as well as different radioimmunoassays for their influence on ET-1 measurement. Recovery of ET-1 depended on the extraction procedure, the type and size of the extraction columns and on the biological matrix itself. Incomplete removal of matrix components by the extraction leads to the formation of particulate matter in the evaporated eluate. When dissolved in assay buffer, ET-1 was found to be absorbed to and only partly released from these particulates, so that it was not accessible for measurement in a radioimmunoassay. This was the case for all extraction procedures investigated except for that involving acetic acid. HPLC analysis of spiked samples revealed that ET-1 is in part degraded during extraction, most probably to Meth-sulphoxide ET-1. Dilution curves of synthetic pure ET-1 standards from different suppliers, prepared either in plasma with subsequent extraction or in assay buffer of the respective radioimmunoassay, resulted in considerable differences in the measured values for ET-1 immunoreactivity. Every radioimmunoassay tested had a specific pattern of recognizing different synthetic ET-1 standards. In conclusion, the measurement of ET-1-immunoreactivity is strongly influenced by the experimental conditions of sample preparation as well as by the radioimmunoassay employed. PMID- 8202642 TI - Tumors showing skeletal muscle differentiation. Introduction. PMID- 8202643 TI - Extracardiac rhabdomyomas. AB - Extracardiac rhabdomyomas are divided into three subtypes: adult rhabdomyomas (ARs), fetal rhabdomyomas (FRs) and genital rhabdomyomas (GRs), each of which has characteristic clinicopathologic features that facilitate their diagnosis. Rhabdomyomas are invariably benign and show varying degrees of skeletal muscle differentiation by electron microscopy and immunohistochemistry. The etiology of these lesions is not understood; however, there is cytogenetic evidence to indicate that ARs are probably neoplastic in origin. The differential diagnosis of rhabdomyomas includes granular cell tumors and hibernomas for ARs, rhabdomyosarcomas and fibromatosis for FRs, and sarcoma botryoides and vaginal polyps for GRs. Identification and investigation of these lesions provide opportunity for gaining insight into skeletal muscle tumor differentiation and skeletal-muscle tumors in general. PMID- 8202644 TI - The diagnosis and classification of childhood rhabdomyosarcoma. AB - Although the typical subtypes of embryonal, botryoid, alveolar, and pleomorphic rhabdomyosarcoma are easily recognized by simple light microscopic examination, poorly differentiated forms are difficult to diagnose and classify. The availability of markers connoting simple myogenous or skeletal muscle differentiation has contributed tremendously to the diagnosis of even poorly differentiated rhabdomyosarcoma. Definition of typical and minimal ultrastructural criteria has also been instrumental. Proper classification of rhabdomyosarcoma into subtypes with prognostic significance has been a difficult task. Although most pathologists have accepted the original classification scheme of embryonal, botryoid, alveolar, and pleomorphic rhabdomyosarcoma, they have used variable histologic criteria to define the various subtypes. Most of the major discrepancies occurred in the definition of embryonal versus alveolar rhabdomyosarcoma, especially in those cases that required establishment of minimal criteria. For example, poorly differentiated round-cell rhabdomyosarcoma has frequently been erroneously classified as embryonal, because of the absence of an alveolar pattern. This variety has been recognized as a form of alveolar (solid alveolar) rhabdomyosarcoma by the National Cancer Institute (NCI) scheme. Comparative analysis of several proposed classification schemes has led to the establishment of well-defined criteria for the major subtypes of rhabdomyosarcoma and to the recognition of subtypes with prognostic significance. PMID- 8202645 TI - The molecular basis of skeletal muscle differentiation. AB - In recent years, significant advances have been made in understanding the molecular mechanisms involved in the regulation of skeletal-muscle differentiation. This review focuses on the role of the MyoD family of myogenic transcription factors that includes MyoD, myf-5, myogenin, and MRF4 (herculin or myf-6) in myogenesis. Members of this family share sequence homology for the basic-helix-loop-helix (bHLH) regulatory motif. The basic domain is required for DNA binding, whereas the HLH domain is required for dimerization. The bHLH motif confers both properties of transcriptional activation of muscle specific genes and inhibition of cell growth through collaboration with the E2A gene products (E12 and E47) and the retinoblastoma gene product (pRB). The functions of the MyoD family can be suppressed through inhibition of their expression or activity by various factors. These include peptide growth factors (FGF and TGF-beta), immediate early gene products (Fos, Jun and Myc), other oncogene products (Ras, Src), the Id protein, and innervation. The use of gene-knockout animal models has shown that there is some degree of functional redundancy in that inactivation of either MyoD or myf-5 has no effect on muscle development, whereas inactivation of both genes results in an absolute lack of muscle cells. In contrast, the inactivation of myogenin alone results in mice with gross deficiency of mature muscle. PMID- 8202646 TI - Rhabdomyosarcoma in adults. AB - Rhabdomyosarcomas occur in adults in one of two forms; as sporadic cases of the juvenile histological types and more commonly, if controversially, as the major adult form, pleomorphic rhabdomyosarcoma. This review documents the historical background to the fluctuating diagnostic popularity of pleomorphic rhabdomyosarcoma, together with a presentation of its defining clinicopathologic characteristics, and presents the clinicopathologic features of the juvenile types as they occur in adults. The concept of pleomorphic rhabdomyosarcoma as a distinct clinicopathologic entity, presenting as an aggressive, predominantly spindle-cell tumor arising in the skeletal musculature of middle-aged adults and defined by the presence of large, pleomorphic tumor cells, which show, at least focally, immunophenotypic or ultrastructural sarcomeric muscle differentiation, is discussed and supported. PMID- 8202647 TI - Alveolar soft-part sarcoma: a new type of rhabdomyosarcoma? AB - Alveolar soft part sarcoma (ASPS) was described as a distinct entity in 1952. ASPS mainly affects young adults, with a slight prevalence of female patients. It arises in the extremities, trunk, and head and neck region. Metastases are frequent and are mainly localized to lungs, brain, and bone. Local recurrences are rare if the primary tumor is completely excised. Adjuvant chemotherapy or radiotherapy are not useful. Death eventually supervenes, after several years, in most of the patients. Histogenesis and differentiation of ASPS, since its first description, have remained a matter of controversy. Many hypotheses have been taken into consideration, among which neural and muscular differentiation are the most plausible. The finding that intracytoplasmic crystals, present in most of the cases, are composed of actin, and the immunocytochemical localization in ASPS of several muscular markers, such as actin (skeletal and smooth muscle actin), desmin, and MyoD1 are all features that point towards skeletal muscle differentiation. PMID- 8202648 TI - Non-germ-cell or teratomatous malignant tumors showing additional rhabdomyoblastic differentiation, with emphasis on the malignant Triton tumor. AB - Non-germ-cell or teratomatous malignant tumors showing additional rhabdomyoblastic differentiation can be divided into three groups. Group I consists of tumors with only sarcomatous differentiation. Included in this group are malignant mesenchymoma, dedifferentiated chondrosarcoma, and the dedifferentiated retroperitoneal liposarcoma. Epithelial or Sertoli-Leydig cell elements represent the second component of tumors in group II. The best known tumor in this group is the malignant mullerian mixed tumor, but other well described tumors with rhabdomyosarcomatous differentiation are the carcinosarcoma, mullerian adenosarcoma, Sertoli-Leydig cell tumor, mammary cystosarcoma, and blastomas. Most of the tumors in groups I and II are derived from mesenchymal tissue. A neuroectodermal origin is shared by all tumors in group III. This includes the medulloblastoma, retinoblastoma and, most frequently, the malignant Triton tumor. The tumors in all three groups are clinically malignant to a varying degree. PMID- 8202649 TI - Foundations of medical diagnosis: what actually are the parameters involved in Bayes' theorem? AB - Three decades ago, the thesis was adduced that setting diagnostic probabilities requires, by the inherent nature of diagnosis-pertinent medical knowledge, the use of Bayes' theorem. That paper was both vague and inconsistent in its delineation of the nature of the parameters involved in this formulation, and subsequent authors have only added to the confusion. Nevertheless, that thesis has been, and continues to be, enthusiastically embraced by clinical scholars. We here posit what those parameters must be taken to represent in principle; and this explication reveals that their quantification poses generally unsurmountable epistemologic challenges. The implication of this is not that informed setting of diagnostic probabilities is generally infeasible. Our conclusion is, instead, that the seminal thesis was founded on an untenable pair of premises about the nature of scientifically attainable knowledge pertinent to diagnosis. PMID- 8202650 TI - Fisher's game with the devil. AB - The publication of Fisher's correspondence on statistics has shed new light on his views on randomization. Quotations from this correspondence and from other works of Fisher are used to illustrate the role of randomization in clinical trials. It is concluded that Fisher's views not only are coherent but, despite having been developed over 60 years ago and with particular reference to agricultural experiments, are still relevant to the planning and analysis of clinical trials today. PMID- 8202651 TI - Comparative exposure ratios: a non-parametric, multifactor technique for case control studies. AB - The odds ratio in a two-by-two table is widely used in case-control studies to measure association between disease and a binary risk factor. In this article we propose a more general measure of association, the comparative exposure ratio (CER), which is the ratio of the number of case-control pairs where the case has greater exposure divided by the number where the control has greater exposure. In simple cases, the CER is an odds ratio or a weighted combination of odds ratios. In more general cases, a CER continues to measure association even when an odds ratio computation is not feasible. Moreover, CERs improve on odds ratios in several ways: they do not require binary risk factors, or a choice of the scale of measurement of continuous risk factors; they make it possible to investigate multiple risk factors simultaneously, without multivariate parametric assumptions; they also can be used to detect patterns that might indicate possible causal pathways. We illustrate how various choices of the definition of 'greater exposure' make the CER a powerful and flexible tool. We give expressions for confidence intervals for CERs, and verify in a pilot simulation that they are valid. Finally, we illustrate with a case-control study of cervical dysplasia how exploratory inference using CERs can be carried out. PMID- 8202652 TI - Analysis of the wideband external pulse: an application of graphical methods. AB - This paper demonstrates the power of statistical graphics in gleaning information from very large medical data sets. In the case of the particular data set described here (the wideband external pulse signal) little was known about the shape of the signal and the relationship of that shape to the characteristics of the related physical system, the cardiovascular system. Previous numerical statistical analyses of the data were unfruitful in finding the important relationships which were easily discovered through the appropriately designed graphics. The paper also describes the process of designing graphics to help in discovering the important relationships in the data. PMID- 8202653 TI - Importance of trends in the interpretation of an overall odds ratio in the meta analysis of clinical trials. PMID- 8202654 TI - [Enteral absorption of peptides]. PMID- 8202655 TI - [Cholesterol embolism: a diagnostic puzzle and a therapeutic dilemma]. AB - A well documented and histologically proven case of cholesterol embolism is discussed, and the recent literature is reviewed. This disorder is usually underdiagnosed and commonly detected only at autopsy. Elderly people with atherosclerotic vascular disease are predominantly affected. Cholesterol embolization can occur spontaneously, but it often results from medical interventions such as arterial invasive procedures, vascular surgery, anticoagulation or thrombolytic therapy. Clinical manifestations are manifold, and two distinct patterns are generally observed: a mild peripheral cutaneous form and a severe visceral form that frequently mimics other systemic diseases. Transient eosinophilia is an important laboratory finding, and it is present in about 80% of the cases. Cholesterol crystals are rarely found in retinal arteries, and premortem diagnosis is established most commonly by biopsy of the muscle, skin or kidney. The role of various therapeutic modalities is still controversial and does not seem to change the course of this frequently fatal disease. The treatment is symptomatic, and the surgical correction of the embolic source is recommended only in the case of peripherally embolizing stenotic lesions. The most effective measures are prevention and the identification of patients at risk. In these patients the aforementioned precipitating events should be avoided, or the potential risk must be carefully weighed against the possible benefits in this particularly fragile group of patients. PMID- 8202656 TI - [Dynamic obstruction of the left ventricular outflow tract: surgical problems]. AB - Dynamic subaortic obstruction caused by septal hypertrophy may worsen the hemodynamics in some patients after heart surgery. Resection of the hypertrophied septum allows normal left ventricular function. We describe two patients with subaortic stenosis and a complicated postoperative course following heart surgery and additional resection of the subaortic muscular stenosis. One patient was reoperated because of residual obstruction of the left ventricular outflow tract; the postoperative course was uneventful thereafter. The second patient died after the primary surgery because of low output syndrome and sepsis. The postoperative management of this group of patients is difficult, demanding frequent assessment of the patient's hemodynamic condition and echocardiographic surveillance. PMID- 8202657 TI - [Febrile status, shift to the left and lymphopenia in systemic lupus erythematosus]. PMID- 8202658 TI - [Prinzmetal's variant angina: a case report]. AB - Prinzmetal's angina is a variant of the classic exertion dependent angina pectoris. Typical is the appearance of the symptoms at rest during early morning hours. It is due to spasms in the coronary arteries. Various provocation tests may be used to trigger spasms, among others hyperventilation which leads to vasoconstriction of coronary arteries. The case of a 53-year-old patient with Prinzmetal's angina is described in whom spasms of the right coronary artery could be evoked by hyperventilation. The following pathogenetic mechanisms may be possible in Prinzmetal's angina: disturbed endothelial permeability, endothelial dysfunction, or secretion of vasoconstrictive substances as well as local hypersensitivity of segments disturbed by atherosclerotic lesions to circulating vasoconstrictors. PMID- 8202659 TI - [A case from practice (294). Isocyanate-induced toxic-irritative bronchitis]. PMID- 8202661 TI - Distribution of macrophages in rheumatoid synovial membrane and its association with basic activity. AB - Rheumatoid arthritis (RA) is an inflammatory disease of the synovial membrane, which results in the destruction of joints by inflammatory pannus. The synovial membrane shows proliferation and cellular infiltrates on microscopy with signs of chronic and acute inflammation. Macrophages are thought to play a central role in the pathogenesis of RA. We examined synovial membrane specimens of 21 RA patients using morphological, immunohistological and enzyme histochemical methods for number and distribution of macrophages. We were able to identify 41.5 +/- 8.8% of lining cells as macrophages, depending on the method used. In abundant diffuse lymphocellular infiltrates, 23.4 +/- 11.1% of mononuclear cells were macrophages. In addition, most cells in the region of tumorlike proliferation and a stromal population of fibroblastlike cells were detected by macrophage markers. Although cell number in synovial membrane increases drastically, we did not find correlations between the relative amount of macrophages in these regions and basic activity. Basic activity includes proliferative reaction as well as lymphoplasmacellular and mononuclear infiltration--both signs of an immunopathological process. In contrast, using enzymes or activation markers, there was a clear correlation. We consider that a constant high percentage of macrophages in RA synovial membrane is present regardless of any actual inflammatory process. PMID- 8202660 TI - Serum levels of interleukin 1-beta, tumor necrosis factor-alpha, soluble interleukin 2 receptor and soluble CD8 in seronegative spondylarthropathies. AB - Seronegative spondylarthropathies are disorders with the same predisposing antigen, namely HLA B27, a class I molecule of the HLA system. The mechanisms of the different diseases are unknown, and there is no proof of immune system participation. We have investigated patients with spondylarthropathies in order to search for an immunological component in the pathophysiology of these disorders, by measuring the serum level of two inflammatory cytokines--IL1 beta and TNF alpha--by a radioimmunological assay and the serum level of two soluble T cell activation markers--soluble IL2 receptor and soluble CD8--by an enzyme linked immunosorbent assay. The choice of soluble CD8 can be explained by the strong link between HLA B27 and spondylarthropathies. Our series compared 24 patients to 24 healthy matched controls. A similar IL1 beta serum level was observed in both groups, while in the patients there was a nonsignificant increase in the TNF alpha level, a significant decrease in the soluble IL2 receptor level and a significant increase in the soluble CD8 serum level. The normal or moderately increased serum IL1 beta and TNF alpha levels in the disease group do not exclude a local role for these cytokines in the synovium or other inflammatory areas. However, we found a higher soluble CD8 serum level in the patient group. Most of these patients were in clinical exacerbation of their disease. As the serum level of soluble CD8 is well correlated with T CD8 lymphocyte activation, our data suggest that this lymphocyte subset is stimulated and consequently probably involved in seronegative spondylarthropathies. PMID- 8202662 TI - Expansion of a B-lymphocyte clone producing IgM auto-antibodies encoded by a somatically mutated VHI gene in the spleen of an autoimmune patient. AB - Seventy-six human B-cell hybridomas were obtained by fusing B lymphocytes from the spleen of a patient with chronic idiopathic thrombocytopenia (ITP). Two independent hybridoma clones producing IgM autoantibodies reacting with platelets and other antigens from both the internal and the external environments were established from this fusion experiment. The IgM autoantibodies produced by the two hybridoma clones were found to be encoded by identical VHDJH and VLJL genes. The comparison of the VHI gene expressed in both hybridomas with the germline equivalent cloned from the patient's DNA showed two somatic mutations in the complementarity-determining regions CDR1 and CDR2 resulting in amino acid replacements. These data suggest the selection and expansion of an autoantibody producing B-cell clone in the spleen of an ITP patient, probably as a result of (auto)antigen-driven stimulation. PMID- 8202663 TI - Inhibition of mitogen-induced response of human peripheral blood mononuclear cells by bucillamine, a new antirheumatic sulfhydryl drug. AB - The mechanism of action of bucillamine, [N-(2-mercapto-2-methylpropionyl)-L cysteine] (BC), a novel antirheumatic drug that is used in patients with rheumatoid arthritis (RA), was compared with that of D-penicillamine (DP). BC inhibited phytohemagglutinin (PHA)-induced DNA synthesis of peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner, and this inhibition occurred both in the presence and absence of copper, whereas DP-induced inhibition required the presence of cupric ions. Significant inhibition of DNA synthesis was observed at a BC concentration of 10 micrograms/ml. The disulfide form of BC, but not DP disulfide, suppressed the proliferation of PBMCs. After preincubation of human peripheral blood T lymphocytes or Mos with BC or DP, these cells were combined and the overall PHA response was estimated. Inhibition of the PHA response was observed following pretreatment of either T lymphocytes or Mos with BC, whereas inhibition was attained only when T lymphocytes were pretreated with DP and copper. As sulfhydryl agents produce hydrogen peroxide in the presence of cupric ions, the effect of catalase on DP- and BC-induced inhibition of PBMC DNA synthesis was examined. Catalase partially reversed the BC-induced inhibition of DNA synthesis of PBMCs, and it restored the inhibition by DP and copper almost to the control level. These results suggest that BC suppresses the function of both T lymphocytes and Mos in the mitogen response of PBMCs, whereas the action of DP is targeted at T lymphocytes. PMID- 8202664 TI - Monospecific but not polyreactive human hybridoma rheumatoid factors exhibit preferential binding specificities for IgG3 and IgG4. AB - Among 38 human hybridoma-derived monoclonal rheumatoid factors (RFs) generated from patients with either rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE), two groups of RFs can be identified. Monospecific RFs were derived primarily from patients with RA and are characterized by a binding specificity for IgG3 and/or IgG4. Polyreactive RFs were derived largely from patients with SLE and show a broader pattern of reactivity to all four isotypes of IgG. Neither population of RFs was exclusive to either disease. The binding specificities identified appear to be different from the RFs isolated from patients with mixed cryoglobulinemia and may reflect a different antigen selection mechanism. PMID- 8202665 TI - Seronegative spondylarthropathies in HIV-infected patients: further evidence of uncommon clinical features. AB - Reiter's syndrome and reactive arthritis in individuals with human immunodeficiency virus (HIV) infection are characterized by severe and persistent arthritis, intense enthesopathy, and poor response to treatment. These uncommon clinical features suggest a direct role of HIV in the pathogenesis of seronegative spondylarthropathies. We report on widely differing clinical features in two HIV-infected patients with undifferentiated seronegative spondylarthropathy or reactive arthritis. Both patients were HLA-B27-positive. The first patient presented with heel swelling and dactylitis ("sausage" toes). Subsequently he developed polyarticular erosive arthritis. The clinical course was complicated by fulminant ulcerative colitis leading to hemicolectomy. After hemicolectomy, a temporary resolution of arthritis occurred. In the second patient, heel swelling and polyarticular arthritis occurred 2 months after Shigella dysentery. After 3 years of continuing joint inflammation, he presented with a Jaccoud-like arthropathy. In a cohort of 700 HIV-infected patients receiving continuous care in our department, these were the only patients with seronegative spondylarthropathy observed between 1984 and 1992. PMID- 8202666 TI - Remitting seronegative symmetrical synovitis with pitting edema: an adult case with excellent prognosis. PMID- 8202668 TI - [Is the activated partial thromboplastin time suitable for monitoring of thrombosis therapy with high-dose standard heparin?]. AB - The activated partial thromboplastin time (aPTT, PTT) is widely used to monitor therapeutic anticoagulation with standard heparin. However, it has been known for some time that PTT reagents obtained from various manufacturers display different sensitivities to heparin--a fact which often is not taken into account. The study deals with the question whether the sensitivity of the PTT to heparin is additionally influenced by the decrease in the vitamin K-dependent coagulation factors such as occurs after starting oral anticoagulation (OAC). In in-vitro studies the reaction of the PTT was observed after addition of different amounts of heparin to normal plasma, to plasma taken after the start of OAC and during stable OAC. The results show that the PTT tends to be more sensitive to heparin as soon as oral anticoagulation is initiated. This phenomenon already occurs at an early stage of anticoagulant intake where only factor VII is markedly reduced but prothrombin concentration is still in an almost normal range and therefore a clinically sufficient effect of OAC is not to be expected. Identical results are obtained with plasma samples of heparin treated patients before and after the start of OAC; in addition, a scattering of the PTTs is obvious. This leads to overestimation of heparin concentrations and a consequent reduction of dosage at an early, still insufficient stage of OAC. In contrast, the thrombin time shows- independently of OAC--a good correlation to heparin concentrations. Therefore the thrombin time is more appropriate to monitor heparin therapy in the phase when oral anticoagulation is started. PMID- 8202667 TI - [Preventive antituberculosis chemotherapy in 250 patients of the antituberculosis outpatient clinic in Lausanne]. AB - Between 1987 and 1990, 250 patients seen at the TB dispensary in Lausanne, Switzerland, received preventive antituberculous chemotherapy. All were tuberculin positive and had a further risk factor for the development of tuberculosis (recent contact with an infectious patient/recent conversion of the tuberculin test, fibrotic lesions on chest X-ray) or were young subjects who had recently immigrated from a country with high endemic tuberculosis. The group comprised 155 asylum seekers and refugees, 29 foreign workers, 24 foreign students and 42 Swiss citizens or long-term residents. 150 patients were detected by routine screening at entry into Switzerland, 33 by contact tracing, and 61 for other reasons. 165 were men (mean age 24 years) and 85 women (mean age 20.5 years). 191 subjects (76%) followed the prescribed isoniazid treatment for 6 months or more, 50 followed it for less than 6 months and 9 never started it. The treatment was interrupted 36 times due to lack of compliance, 4 times for medical reasons independent of the medication and 5 times due to pregnancy. 33 patients complained of side-effects (gastrointestinal in 20, cutaneous in 9, other in 4) which required interruption of treatment in 14. Liver enzymes were checked in 100 patients; significant elevation of the transaminases was observed in 3 patients who simultaneously complained of gastrointestinal side effects. In spite of practical problems, it seems possible to prescribe a full course of preventive antituberculous chemotherapy in the majority of patients where the treatment is indicated, and even in asymptomatic patients with whom communication is frequently difficult.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202669 TI - [Alcoholic pellagra encephalopathy: an underestimated treatable entity]. AB - Alcoholic pellagra-encephalopathy is an underestimated entity, which is characterized by alteration in the level and content of consciousness, marked oppositional hypertonus and myoclonus. This entity should be included in the differential diagnosis of encephalopathy in ethanol abusers. The spontaneous course is potentially lethal. Therapy consists of substitution of nicotinic acid in the form of nicotinamide. It is emphasized that any chronic ethanol abuser with neurological symptoms should receive substitution of all B-group vitamins including nicotinamide. PMID- 8202670 TI - [Epidermoid carcinoma of the esophagus and Fanconi's anemia]. AB - We report the case of a 36-year-old female with Fanconi's anemia who developed a squamous cell carcinoma of the esophagus which was treated by surgery. In the long term, Fanconi's anemia is associated with a high incidence of acute leukemia, liver tumors or squamous cell carcinomas of various organs. The high chromosome breakage of this disease is assumed to be a predisposing factor for malignant development. This elevated tumor incidence must be appreciated if early diagnosis and appropriate therapy are to be initiated. PMID- 8202671 TI - [Effect of the menstrual cycle on the reproducibility of anorectal manometry]. AB - The influence of the menstrual cycle on the reproducibility of anorectal manometry was investigated in 6 healthy volunteers (median age 29 years) without hormonal treatment, who were studied during the follicular and the luteal phases and during the menstruation phase. The intra- and interindividual variations were compared by calculating KENDALL's concordance coefficient. The following results were obtained (mean +/- SD): sphincter length (41 +/- 4 mm), anal pressure at rest (79 +/- 6 cm H2O) and during voluntary contraction (167 +/- 23 cm H2O), threshold volume for the anorectal reflex (12 +/- 3 ml), duration after 20 ml (24 +/- 7 seconds), after 40 ml (47 +/- 3 seconds) and variation of the rectoanal inhibitory reflex after 40 ml (25 +/- 9 cm H2O), threshold volume of rectal sensation (16 +/- 5 ml), volume of constant perception after 30 seconds (101 +/- 27 ml), maximum tolerable volume (212 +/- 18 ml) and rectal pressure during maximum tolerable volume (23 +/- 6 cm H2O). For all of the above parameters, the intra-individual variations were not higher than the inter-individual variations. We therefore conclude that the menstrual cycle does not influence the reproducibility of anorectal manometry in the healthy woman. PMID- 8202672 TI - [Evaluation of advertisements of weight-reducing cures in the press]. AB - The aim of this study was to obtain an overview of the weight control programmes advertised in the Swiss press and to explore them in terms of their scientific basis and success rates. 875 advertisements and questionnaires from 507 patients and 52 advertisers were analyzed. Scientifically questionable methods usually remained ineffective. In contrast, methods based on a reasonably balanced long term diet proved more successful. With the latter, an average weight loss of 15 kg was achieved in 32 weeks at a cost of Sfr. 456.-. In doing so, 56.1% of the patients reported they had reached their target weight and it was entirely or partly maintained for a prolonged period by 39.6%. In terms of cost/benefit ratios, scientifically based programmes which follow the principles of physiology and behavioural psychology are the most favourable, and physicians should know and recommend them. Unfortunately, in Switzerland health insurance still pays for programmes which were shown to be unsuccessful in the long term, such as appetite lowering medication, or costly, such as short-term courses of treatment in hotels. PMID- 8202673 TI - [Reactivation of hepatitis B following withdrawal of chloroquine]. AB - A severe flare-up of chronic hepatitis B infection with liver cell insufficiency has been observed in two patients after discontinuation of chloroquine administered either as malaria prophylaxis or as treatment of presumed rheumatoid arthritis. Chloroquine is known to inhibit the association of the major histocompatibility complex type II with hepatitis B virus antigens, thereby inhibiting T-cell mediated lysis of infected cells. Furthermore, it inhibits uptake of duck hepatitis B virus by duck liver cells. These in vitro studies and our clinical observations suggest that chloroquine inhibits the lysis of hepatitis B virus infected hepatocytes. Withdrawal of chloroquine in patients with chronic hepatitis B virus infection can lead to a rebound immune response manifesting as a reactivation of hepatitis B, similar to that observed after steroid withdrawal. PMID- 8202674 TI - [Cholecystectomy today. A prospective study]. AB - Between 13 June 1990 and 12 June 1993, we performed 1145 consecutive cholecystectomies. 127 patients who had undergone additional surgery were excluded from the prospective study. Of the remaining 1018 patients, 806 (78.2%) underwent laparoscopic cholecystectomy. The conversion rate to open procedure was 11.2% (90/806). The operative morbidity associated with laparoscopic cholecystectomy was 2.1% (17/806) and with open surgery 1.9% (4/212); mortality was 0.12% (1/806) and 0.47% (1/212) respectively. The reoperation rate after laparoscopic cholecystectomy was 0.6% (5/806). Reoperation was performed for lesions of the common bile duct, bleeding, and abscess formation. If the indications for open cholecystectomy are respected the morbidity and mortality were low for both laparoscopic and conventional cholecystectomy. PMID- 8202675 TI - [Acute cholecystitis: indication for emergency laparoscopic cholecystectomy?]. AB - Between 1989 and 1992, 43 patients underwent laparoscopic cholecystectomy for acute cholecystitis. Conversion to open cholecystectomy was necessary in one case (2.3%). Morbidity was 14%, i.e. 7% local complications and 7% systemic complications. No lesions of the CBD occurred and no reoperations or reinterventions were required. Mortality was 0%. The main determining factor for the technical difficulty of laparoscopic cholecystectomy was the lapse of time between onset of symptoms and operation. We show the duration of laparoscopic cholecystectomy during the first 6 days of acute cholecystitis (mean 104 min) is statistically different in the following groups of patients (7-14 days p = 0.0049; 15-21 days p = 0.0037; Mann-Whitney-U-test). We therefore conclude that laparoscopic cholecystectomy is a safe method in acute cholecystitis and that the ideal time of operation is as soon as possible within the first 6 days after onset of illness. Performance of laparoscopic cholecystectomy should not be delayed during this period of acute cholecystitis. If the procedure is carried out by well trained laparoscopic surgeons the risks and complications are equal to those of open cholecystectomy. PMID- 8202676 TI - [The value of ERCP in the diagnosis and therapy of complications of laparoscopic cholecystectomy]. AB - Biliary complications are more frequent in laparoscopic than in open cholecystectomy. The aim of the study was to evaluate the diagnostic and therapeutic value of endoscopic retrograde cholangiopancreatography (ERCP) in the management of complications of laparoscopic cholecystectomy. We therefore report on the result of 49 ERCP after laparoscopic cholecystectomy done at our department between January 1991 and March 1993. Patients were referred from 16 different surgical institutions. In 29 cases endoscopic sphincterotomy was performed without complications. Indications for ERCP were "persistent biliary pain" (n = 27), bile leakage (n = 7), pancreatitis (n = 5), abscess (n = 5), painless jaundice (n = 3) and asymptomatic bile duct stone in routine cholangiography (n = 2). In the group of patients with "persistent biliary pain" we found bile duct stones in 12 (80%) of 15 cases with cholestasis and in 3 (30%) of 10 without cholestasis. The stones were endoscopically removed after sphincterotomy. In 2 patients without cholestasis, cannulation of the bile duct failed. 7 patients showed biliary leakage, 4 from inadequate clipping of the cystic stump (2 in combination with a common bile duct stone), 2 from the hepatic duct and 1 from insufficient anastomosis after reconstruction of a common bile duct. After endoscopic sphincterotomy and, if necessary, stone extraction by Dormia basket, leakage from the cystic stump and hepatic duct healed. The insufficient common bile duct anastomosis required reconstruction by hepaticojejunostomy. Three of 5 patients with postoperative pancreatitis had common bile duct stones, while one with chronic pancreatitis had a concrement in the pancreatic duct which was endoscopically removed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202677 TI - [Hematological reference values for foals in the first two months of life]. AB - Hematologic reference values were established in 18 healthy foals in the first two months of life. Blood samples were collected prior to colostrum consumption and at 30 hours, 1 week, 3, 5, 7 and 9 weeks of age. PCV, Hb and RBC decreased during the first week and RBC, but not PCV and Hb, increased toward the end of the second month. With the exception of the sample at 1 week, the foals had mean RBC values significantly higher than those of controls. Mean MCV and MCH did not change during the first week, but decreased slightly thereafter; all means were smaller than in controls. The numbers of neutrophils increased mainly during the first week, and the numbers of lymphocytes increased gradually during the first two months. The mean N:L-ratio was highest at 1 week and lowest at 5 weeks. PMID- 8202678 TI - The long-term influence of biotin supplementation on hoof horn quality in horses. AB - The influence of dietary biotin in horses with brittle hoof horn and chipped hooves was investigated in a long-term study, which was performed over a period from one to six years. 97 horses received 5 mg of biotin per 100 to 150 kg of body weight, per os, daily; 11 horses were not supplemented with biotin and served as controls. The hooves of all horses were evaluated macroscopically every three to four months. Hoof horn specimens of the proximal wall were examined histologically and physically in 25 and 15 horses, respectively. The tensile strength of normal coronary horn was 60 N/mm2 or greater; it was reduced in areas of histological alterations, the lowest value being 20 N/mm2. The hoof horn condition of the biotin-supplemented horses improved after eight to 15 months of supplementation as determined by macroscopic and histologic examinations. The hoof horn condition of most control horses remained constant throughout the study. The growth rate of the coronary horn of horses supplemented with biotin and of control horses was the same. The hoof horn condition deteriorated in 7 of 10 horses after biotin supplementation was reduced or terminated. It was concluded that biotin should be continuously supplemented at the full dosage in horses with severe hoof horn alterations. PMID- 8202679 TI - [Short anesthesia in rats: an injection or an inhalation anesthesia]. AB - First we describe the application of an injection anaesthesia in a specific strain of rats and test its usefulness under practical conditions. Application (i.p.) of the described dose according to the animals body-weight resulted in an acceptable anaesthesia, which lasted approximately 50 minutes in male rats and 80 minutes in female rats. Next we compare the common ether anaesthesia with an other inhalation anaesthesia (Methoxyflurane) which, by using a self-made mask, could be prolonged without any problem for at least 15 minutes ("prolonging time"). A correlation was found between the duration of the prolonging-time and the awakening time. Inhalation anaesthesia using Methoxyflurane obviously affected the animals health and well-being less than the conventional ether anaesthesia. PMID- 8202680 TI - [Regulation of gene transcription in eukaryocytes]. PMID- 8202681 TI - [Alzheimer's disease and cholinesterase]. PMID- 8202682 TI - [Amyloid precursor protein and Alzheimer's disease]. PMID- 8202683 TI - [Molecular biology of the prolactin receptor]. PMID- 8202684 TI - [Presynaptic acetylcholine autoreceptor and its role in neuromuscular transmission]. PMID- 8202685 TI - [Role of the nucleus reticularis paragigantocellularis lateralis in the pain modulating system]. PMID- 8202686 TI - [Peptidergic regulation in the cerebral vessels]. PMID- 8202687 TI - [Study on initiation of human lung carcinogenesis]. PMID- 8202688 TI - [Involvement of endorphins in the central mechanism of hypoxia-induced respiratory inhibition]. PMID- 8202689 TI - [Hepatocyte growth factor]. PMID- 8202690 TI - [Progress on the study of hepatocyte growth factor-cytosol]. PMID- 8202691 TI - [Interleukin-8 and inflammation]. PMID- 8202692 TI - [The ventral root afferent fibers and their physiological function]. PMID- 8202693 TI - [Interaction of biological action between endothelin and atrial natriuretic peptide]. PMID- 8202694 TI - [Interaction of blood platelets between vascular endothelium and vascular smooth muscle]. PMID- 8202695 TI - The fate of environmental contaminants in the food chain. AB - This paper reviews the major sources of industrial environmental pollutants that may give rise to organic contaminants in foods, indicates which foods tend to be most frequently found to be contaminated and summarises available data on levels of occurrence. Polycyclic aromatic hydrocarbons (PAHs), phthalic acid esters, polychlorinated dibenzodioxins and dibenzofurans (PCDDs and PCDFs), polychlorinated biphenyls (PCBs) and organic phosphates are widespread environmental contaminants which have all been detected in foods. Estimates of exposure to these contaminants from total diet and other studies are summarised. Some pollutants such as volatile halocarbons and benzene tend to only occur as localised contaminants for which targeted monitoring of foods is necessary. The most difficult area is regarded as the detection of previously unrecognised contaminants in foods for which some possible approaches are described. PMID- 8202696 TI - Safe food manufacturing. AB - Food safety is a growing preoccupation of the health authorities and the major food companies in any European country. All the aspects of food manufacturing, from the raw materials until the product is consumed have to insure they are innoxious to human health, eliminate any harmful effects related either to food handling or consumption in domestic or common eating places, as well as protect, as much as possible, our environment. Thus, the food manufacturer has to examine step-by-step the security of the agro-cultures, their composition, but also the possible residues of pollutants and contaminants, or chemicals used to protect them against various pests and determine the possible loss or retention of these substances during technological processes. Animal raw materials should not contain veterinary drug residues or an abnormal amount of some components that result from inadequate feeding. Care should be taken to ensure the security of foods manufactured by biotechnology processes. The organisms and the whole processes used in food biotechnologies should eliminate any impurities. Any minor food ingredients, such as food additives, are under a permanent revision from the point of view of their safety. The industry reacts immediately if any justification requires that a particular food additive should not be used. In other words all the raw materials must conform to their specifications. Technological processes must create a food with an adequate microbiological quality, e.g. free of pathogens and their toxic metabolites. Any danger of microbiological contamination or accidental pollution, such as mechanical particles, chemical substances, etc. should be eliminated. The particular role of food packaging is crucial, since this is a barrier to protect the food against further parasites or microbial contamination and preserve the food from alterations due to enzymatic reactions that require particular oxygen and water activity conditions. The packaging should also protect against possible criminal damage. In addition, the material of packaging should not allow micro-migration to the food. It should be inert against its food content. Another aspect of food packaging that has to be taken into account is its recovery and recyclability. Finally, the food manufacturer has to ensure that the nutritional value of the product does not diminish through its shelf-life. The consumer should be advised about the effects of culinary practices since some of them, such as deep frying or grilling under certain circumstances, may create undesirable substances potentially harmful to human health. The food manufacturing in the context of the environment protection requires a separate issue.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8202698 TI - Funding of NIMH extramural research. PMID- 8202697 TI - Environmental pollution and human health. AB - Contacts of humans with chemicals from the environment occur via air, water or food. In the past most attention was paid to the contamination of water. Well developed and stringent legislation exists in most countries, although health impairments never occurred from environmental chemicals in drinking water. Xenobiotics in water mainly have a marker function for the general pollution of the environment. Therefore measures to detect and eliminate the sources of contamination are often inappropriately taken. For some persistent and (usually) lipophilic xenobiotics in food, especially from animal origin, acts as carrier. The lipophilic persistent chlorinated compounds, such as DDT, PCBs and dioxins and the heavy metals lead, cadmium and mercury are accumulated in livestock and are there leading to much higher concentrations than in the environment. So far these compounds have not yet reached concentrations which are representing a health risk. A range of environmental chemicals coming from the air act directly on the site of first contact through their cytotoxic property. For many of them the margin of safety is low or even non-existent. Inorganic acid anhydrides, such as SO2, SO3 or NOx often occur in industrialized areas at levels affecting the pulmonary function of susceptible people, such as asthmatics or patients with chronic bronchitis. Ozone and photochemical smog represent another group of important environmental irritants. The intake of airborne lead has diminished in the last 20 years by a factor of 2-3 as a consequence of the most remarkable decrease in the use of leaded gasoline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8202699 TI - Polio in Russia. PMID- 8202700 TI - Carcinogenicity of chloroform. PMID- 8202701 TI - U.N. set to merge AIDS programs. PMID- 8202703 TI - Animal tests take back seat to clinical data. PMID- 8202702 TI - Tamoxifen: hanging in the balance. PMID- 8202704 TI - HHMI: a dynasty in the making. PMID- 8202705 TI - Vaccine research. New society seeks common ground. PMID- 8202706 TI - Hepatitis study. Drug trial deaths deemed unavoidable. PMID- 8202707 TI - Clinical trial monitoring: hit or miss? PMID- 8202708 TI - Problems in clinical trials go far beyond misconduct. PMID- 8202709 TI - How nature builds the pigments of life: the conquest of vitamin B12. AB - In part because humans cannot synthesize vitamin B12 and must obtain it from organisms that produce it and because B12 deficiency leads to pernicious anemia, it has been important to understand how microorganisms build this quite complex substance. As shown here, an interdisciplinary attack was needed, which combined the strengths of genetics, molecular biology, enzymology, chemistry, and spectroscopy. This allowed the step-by-step synthetic pathway of B12 to be elucidated, and this approach has acted as a model for future research on the synthesis of substances in living organisms. One practical outcome of such an approach has been the improved availability of B12 for animal feedstuffs and human health. PMID- 8202710 TI - The structural basis of sequence-independent peptide binding by OppA protein. AB - Specific protein-ligand interactions are critical for cellular function, and most proteins select their partners with sharp discrimination. However, the oligopeptide-binding protein of Salmonella typhimurium (OppA) binds peptides of two to five amino acid residues without regard to sequence. The crystal structure of OppA reveals a three-domain organization, unlike other periplasmic binding proteins. In OppA-peptide complexes, the ligands are completely enclosed in the protein interior, a mode of binding that normally imposes tight specificity. The protein fulfills the hydrogen bonding and electrostatic potential of the ligand main chain and accommodates the peptide side chains in voluminous hydrated cavities. PMID- 8202711 TI - Anergic T cells as suppressor cells in vitro. AB - T cell-mediated suppression is an established phenomenon, but its underlying mechanisms are obscure. An in vitro system was used to test the possibility that anergic T cells can act as specific suppressor cells. Anergic human T cells caused inhibition of antigen-specific and allospecific T cell proliferation. In order for the inhibition to occur, the anergic T cells had to be specific for the same antigen-presenting cells (APCs) as the T cells that were suppressed. The mechanism of this suppression appears to be competition for the APC surface and for locally produced interleukin-2. PMID- 8202712 TI - Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase. AB - A homozygous mutation in the kinase domain of ZAP-70, a T cell receptor associated protein tyrosine kinase, produced a distinctive form of human severe combined immunodeficiency. Manifestations of this disorder included profound immunodeficiency, absence of peripheral CD8+ T cells, and abundant peripheral CD4+ T cells that were refractory to T cell receptor-mediated activation. These findings demonstrate that ZAP-70 is essential for human T cell function and suggest that CD4+ and CD8+ T cells depend on different intracellular signaling pathways to support their development or survival. PMID- 8202713 TI - ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency. AB - Protein tyrosine kinases (PTKs) play an integral role in T cell activation and differentiation. Defects in the Src-family PTKs in mice and in T cell lines have resulted in variable defects in thymic development and in T cell antigen receptor (TCR) signal transduction. Here, three siblings are described with an autosomal recessive form of severe combined immunodeficiency disease (SCID) in which ZAP 70, a non-Src PTK, is absent as a result of mutations in the ZAP-70 gene. This absence is associated with defects in TCR signal transduction, suggesting an important functional role for ZAP-70. PMID- 8202714 TI - Noradrenergic regulation of cholinergic differentiation. AB - When the sympathetic nerves that innervate rat sweat glands reach their targets, they are induced to switch from using norepinephrine as their neurotransmitter to acetylcholine. Catecholamines (such as norepinephrine) released by nerves growing to the sweat gland induce this phenotypic conversion by stimulating production of a cholinergic differentiation factor [sweat gland factor (SGF)] by gland cells. Here, culture of gland cells with sympathetic, but not sensory, neurons induced SGF production. Blockage of alpha 1- or beta-adrenergic receptors prevented acquisition of the cholinergic phenotype in sympathetic neurons co-cultured with sweat glands, and sweat glands from sympathectomized animals lacked SGF. Thus, reciprocal instructive interactions, mediated in part by small molecule neurotransmitters, direct the development of this synapse. PMID- 8202715 TI - Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci. AB - In spite of recent advances in identifying genes causing monogenic human disease, very little is known about the genes involved in polygenic disease. Three families were identified with mutations in the unlinked photoreceptor-specific genes ROM1 and peripherin/RDS, in which only double heterozygotes develop retinitis pigmentosa (RP). These findings indicate that the allelic and nonallelic heterogeneity known to be a feature of monogenic RP is complicated further by interactions between unlinked mutations causing digenic RP. Recognition of the inheritance pattern exemplified by these three families might facilitate the identification of other examples of digenic inheritance in human disease. PMID- 8202716 TI - Total platinum dose versus platinum dose intensification in ovarian cancer treatment. AB - Multiple in vitro and in vivo studies demonstrate the importance of platinum dose intensity in chemotherapy of advanced ovarian cancer. The relevant areas discussed in this report include (1) retrospective analysis of platinum dose intensity and outcome of ovarian cancer therapy, (2) in vitro human tumor cell line drug assay data, (3) fresh human ovarian tumor cloning data, (4) platinum pharmacokinetics with an emphasis on the relationship between the platinum concentration x time product and cytotoxicity, and (5) prospective clinical studies designed to test the importance of platinum dose intensity alone or platinum dose intensity and total dose. When attempting to design optimal platinum-based therapies for ovarian cancer, it is important to bear in mind the following considerations: (1) both platinum dose intensity and total dose should be increased; (2) to achieve exponential cytotoxicity (eg, up to 10-fold increases in tumor cell kill) by increasing the platinum dose, it is critical to select a platinum dose capable of overcoming inherent drug resistance; (3) carboplatin may be the platinum analogue of choice for dose intensification studies since, unlike cisplatin, it is rarely associated with cumulative nonhematologic toxicity (and as a result can be escalated up to five to six times the standard dose); and (4) the Calvert formula should be used for determining carboplatin dose to safely and accurately target desired drug exposure (as measured by the concentration x time product) and degree of hematologic toxicity. PMID- 8202717 TI - Intraperitoneal cisplatin and carboplatin in the management of ovarian cancer. AB - The intraperitoneal delivery of cisplatin or carboplatin in the management of ovarian cancer is based on a sound pharmacokinetic rationale. Objective responses, including surgically documented complete responses, have been observed in patients with ovarian cancer who have previously responded to systemic platinum-based therapy. A precise role for intraperitoneal cisplatin or carboplatin in the management of ovarian cancer remains to be defined. PMID- 8202718 TI - Further studies to ameliorate toxicity of carboplatin. AB - The introduction of carboplatin as a replacement for cisplatin into treatment strategies against ovarian cancer has ameliorated major toxicities related to cisplatin, but carboplatin-evoked myelosuppression requires further study, especially since the addition of growth factors for bone marrow and hematologic support has been introduced into clinical practice. Since higher doses of platinating agents seem to be related to higher response rates, the protective effect of interleukin-3 on 800 mg carboplatin, a twofold increment over the usual dose, was studied. A modest myeloprotective potency was documented in the second treatment cycle of this aggressive chemotherapy program, but this effect tapered away in subsequent treatment courses, which occasionally included severe side effects (eg, headache, kidney function impairments). Another study addressed the anemia frequently observed with both cisplatin- and carboplatin-based treatment regimens in ovarian cancer, which is probably related to low erythropoietin levels. Very preliminary analysis of an ongoing phase III trial studying two erythropoietin doses given continuously subcutaneously versus a retrospective analysis of a "control group" (drawn from historical data on the occurrence of anemia in cisplatin- and/or carboplatin-treated patients) has shown beneficial effects of erythropoietin during treatment with these platinating agents. PMID- 8202719 TI - Platinum compounds in cervical and endometrial cancers: focus on carboplatin. AB - Drug therapy for cervical cancer is slowly undergoing evaluation in early disease stages, in which it is more likely to make an impact. Cisplatin has been the principal drug used in systemic therapy for all stages, with the possible exception of the radiosensitizer hydroxyurea. Nevertheless, current studies use cisplatin in this role as well. To a limited extent, substitution of carboplatin for cisplatin also has been explored. Conflicting interpretations of carboplatin trials nonetheless support continued study of this drug; its activity is reproducible and it can be combined with radiation therapy in practical dose schedules. The major question in the systemic nonendocrine treatment of endometrial cancer revolves around whether cisplatin adds to results achievable with doxorubicin. Carboplatin, documented as active against this neoplasm, represents a potentially advantageous cisplatin substitute for elderly patients. Moreover, if combination chemotherapy should prove disappointing, single-agent carboplatin may provide the best strategy for palliative therapy. PMID- 8202720 TI - Carcinoma of the uterine cervix: current status and future directions. AB - Based on rigorous interpretation of current evidence, systemic therapy has two roles in the management of carcinoma of the uterine cervix. In patients with advanced or recurrent disease, single-agent chemotherapy constitutes the treatment of choice. The most extensively studied agents are the platinum compounds. Either cisplatin or carboplatin represents a reasonable choice for first-line treatment. There appears to be no significant influence of either dose or schedule on patient benefit. Other agents with clear-cut activity include ifosfamide, dibromodulcitol, and doxorubicin. At this time, there is no scientific basis for the use of combination chemotherapy in advanced or recurrent carcinoma of the cervix. In patients with locoregionally advanced disease (stages IIIB or IVA), radiation plus either hydroxyurea or a combination of cisplatin plus 5-fluorouracil offers an advantage over radiation alone in terms of progression-free interval and survival. In patients with more limited disease, there is no defined role for systemic therapy at the present time. Three goals constitute the focus for current investigational efforts: (1) continued efforts to identify additional highly active drugs are needed; (2) the development of effective combination chemotherapy depends on the use of logically designed combinations of active drugs in well-designed phase III trials with single-agent therapy as the control; and (3) phase III trials seeking more effective combinations of systemic therapy with surgery and/or radiotherapy should continue for not only locoregionally advanced disease but also for more limited carcinoma of the cervix. PMID- 8202721 TI - Immunologic aspects of blood transfusion. AB - For 20 years, clinical reports and laboratory observations have suggested that allogeneic blood transfusion effects important changes in the recipient's immune response. The seminal clinical studies involved dose-dependent improvement in renal allograft survival in patients transfused with allogeneic whole blood, red blood cells, and buffy coat preparations. Subsequently, a burgeoning, but unclear literature proposed that allogeneic blood transfusion decreases survival or tumor free survival of patients who undergo operations for a variety of different malignancies. Similar studies suggest that the risk of postoperative infection increases when patients receive allogeneic blood. Transfusion reportedly improves some patients with Crohn's disease. In summary, these findings have been interpreted as evidence for an immunosuppressive effect of allogeneic blood transfusion. A small prospective study showed that paternal buffy coat infusion decreases the rate of fetal loss in a subset of women with recurrent abortion. These data suggest induction of "tolerance." Laboratory studies confirm changes in lymphocyte subsets, lymphocyte activation, natural killer cell activity, antigen-presenting function, and phagocytic cell function in patients and animals that receive allogeneic blood. The clinical relevance of these observations remains controversial. Allogeneic leukocytes induce expression of latent cell associated viruses (human immunodeficiency virus, cytomegalovirus, Epstein-Barr virus), suggesting further immune-mediated adverse effects of transfusion. The mechanisms and clinical importance of these observations have become areas of intense interest and investigation for transfusion medicine. PMID- 8202722 TI - Recombinant human erythropoietin in the treatment of cancer and chemotherapy induced anemia: results of double-blind and open-label follow-up studies. AB - Anemia associated with advanced cancer is common. Contributing factors include the anemia of chronic disease, chemotherapy, radiation therapy, and bone marrow invasion with tumor. Based on the observation that endogenous erythropoietin (EPO) levels in anemic patients with cancer are inadequate for the degree of anemia, three randomized double-blind, placebo-controlled trials of recombinant human erythropoietin (rHuEPO) treatment in anemic patients with cancer were performed in patients (1) not receiving concomitant chemotherapy (NO CTX), (2) receiving myelosuppressive chemotherapy that did not include cisplatin (CTX-NO PLAT), and (3) receiving myelosuppressive cisplatin-containing chemotherapy (CTX PLAT). In the NO CTX trial, patients were treated with rHuEPO 100 U/kg or placebo subcutaneously (SQ) three times per week for up to 8 weeks. In the CTX trials, patients were treated with rHuEPO 150 U/kg or placebo SQ three times per week for 12 weeks. Four hundred thirteen patients were enrolled (124, NO CTX; 157, CTX-NO PLAT; and 132, CTX-PLAT). In all three trials, patients receiving rHuEPO had a significantly (P < .004) greater increase in hematocrit (HCT) than placebo treated patients. In the two CTX trials combined, rHuEPO-treated patients also had a significantly (P < or = .009) lower transfusion requirement than placebo treated patients after the first month of therapy. Quality of life improved significantly (P < .05) in responding (> or = 6%-point HCT increase without transfusion) rHuEPO-treated patients compared with placebo-treated patients. Overall, no adverse events occurred more frequently in rHuEPO-treated patients compared with placebo-treated patients. Following completion of the double-blind phase, patients received rHuEPO on an open-label basis as needed for correction of anemia with the dose titrated to a maximum of 900 U/kg/wk. During total rHuEPO exposure (either started at the beginning of double-blind therapy for patients initially randomized to rHuEPO or at the beginning of open-label therapy for patients initially randomized to placebo; 363 treated/347 evaluable for efficacy), 40.0%, 56.1%, and 58.3% of the NO-CTX, CTX-NO PLAT, and CTX-PLAT patients, respectively, responded to rHuEPO therapy with an increase of HCT > or = 6% unrelated to transfusion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8202723 TI - Anemia therapy: individual benefit and societal cost. AB - The US health care system is under increasing pressure to lower costs while maintaining quality of care. Providers will be forced to (1) measure the benefits of a particular therapy, and (2) demonstrate that the benefits justify the costs. The major components of therapeutic benefit are survival and quality of life. Chronic anemia may have little impact on survival, but studies have measured significant decrements in quality of life without therapy and increments in quality of life with therapy. This disease also presents important societal financial concerns due to its many competing therapies. The annual cost of treatment can vary from an average of a few dollars for iron supplementation to an average of $6,000 for a course of recombinant human erythropoietin. Physicians need to integrate information on therapeutic outcomes and cost to maximize individual benefit and justify the costs. The choice of therapy for anemia associated with cancer is complex because the onset of the anemia is multifactorial, and the effects of anemia may be masked by the underlying malignancy. There are insufficient data supporting a specific recommendation for transfusion or recombinant human erythropoietin therapy. The current cost conscious environment in the United States presents an opportunity for health care providers to formally document the benefits of anemia therapy and justify the societal costs based on those benefits. Anemia is an excellent example of a condition that allows the formal analysis of disease impact and the effectiveness and cost of therapy because (1) it has multiple therapies, (2) the cost of therapy varies widely, and (3) the therapies have variable benefit depending on the individual patient. Using a model based on chronic renal failure, an outcomes structure was developed by which the impact of anemia and the therapies used to manage it can be measured. Its potential application to anemia in patients with cancer is discussed. PMID- 8202724 TI - Cancer-related anemia: its causes and characteristics. AB - Under normal circumstances, the circulating red blood cell mass is maintained at a level that is constant in each individual, although that level may vary by more than 10% among individuals of the same age and gender. At normal ambient oxygen tension, two factors determine the circulating red blood cell mass: red blood cell life span, which is finite and in humans approximates 120 days; and the rate of effective red blood cell production. To maintain a constant red blood cell mass, therefore, approximately 20 mL of red blood cells must be produced each day to replace those red blood cells lost from the circulation through senescence. Anemia, which may be defined functionally as lack of sufficient red blood cells to maintain adequate tissue oxygenation, develops when the demand for new red blood cells exceeds the capacity of the bone marrow to produce them. This may be due to excessive red blood cell destruction, impaired red blood cell production, bleeding, or any combination of these. Acquired anemia is always a consequence of another disorder, which must be identified to ensure that the corrective therapy is appropriate. In patients with solid tumors, multiple mechanisms for causing anemia have been identified: blood loss that is either intrinsic or iatrogenic; nutritional deficiencies involving primarily iron or folic acid; hemolysis (autoimmune, traumatic, or drug-induced); bone marrow failure due to tumor encroachment, myelofibrosis, or marrow necrosis; infection; inflammation; or simply the presence of a cancer elsewhere in the body. The three noted causes of marrow failure share a common denominator: impaired production of erythropoietin. For any degree of anemia, a patient with cancer produces much less erythropoietin than expected and, therefore, cannot compensate for impaired red blood cell production. Inflammation or infection can exacerbate this situation. Indeed, anemia in patients with cancer appears to behave much like that in patients with chronic renal failure who become anemic because of the inability of the kidneys to produce erythropoietin adequately. The cause of impaired erythropoietin production in patients with cancer who have anemia is not entirely understood, but may be due in part to the production of inflammatory cytokines in response to the tumor. Such cytokines also would be expected to blunt the ability of the bone marrow to respond to the available circulating erythropoietin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8202725 TI - The relationship of erythropoietin and iron metabolism to red blood cell production in humans. AB - Erythropoietin (EPO) is the primary regulator of day-to-day red blood cell production. Secreted by peritubular capillary lining cells in the kidney, EPO circulates in the plasma to interact with target cells in the bone marrow to maintain or stimulate erythropoiesis. The primary target of EPO action is the intermediate-stage erythroid burst-forming unit and the erythroid colony-forming unit (CFU-E). The CFU-E is estimated to have 300 to 400 high-affinity EPO receptors per cell and, in healthy individuals, is the cell with the highest number of receptors in the body. There is some controversy as to whether EPO provides a mitogenic signal to the CFU-E or, rather, prevents programmed cell death (apoptosis). Iron is an essential element for hemoglobin synthesis and its importance has been emphasized in individuals receiving recombinant human erythropoietin (rHuEPO). The administration of rHuEPO to patients with chronic renal failure has resulted in a number of changes in iron metabolism, including the reversal of iron overload as iron is mobilized from storage sites for hemoglobin synthesis. In addition, higher doses of rHuEPO create a state of functional (or relative) iron deficiency that is characterized by a low percent transferrin saturation in the face of adequate iron stores. The value of aggressive iron supplementation in patients receiving rHuEPO has been demonstrated in clinical trials of rHuEPO administration in individuals storing blood for autologous use at the time of surgery. PMID- 8202726 TI - [Nursing care for the elderly patient. A challenge for the Third Millennium]. PMID- 8202727 TI - [Physicians and nurses]. PMID- 8202728 TI - [Stages in the study to assess health professional performance]. PMID- 8202729 TI - [The 108th anniversary of the Artur Ravara School of Nursing]. PMID- 8202730 TI - [The change toward patient-centered care]. PMID- 8202731 TI - [Humanizing the teaching of nursing: time ... and contretemps!]. PMID- 8202732 TI - [Drugs and sexual freedom]. PMID- 8202733 TI - [Evaluating to decide. Does red wine prevent coronary mortality?]. PMID- 8202734 TI - Social sciences and preventive medicine. PMID- 8202735 TI - Frailty and its consequences. PMID- 8202736 TI - Stress and strategies in care systems: the Scandinavian experience. AB - The gap between needs and public care resources will probably expand, and in order to bridge this gap, available resources must be used more adequately and efficiently. Other relevant strategies are to moderate demands on the public resources, either by trying to reduce the demands themselves, and/or by redirecting them towards the private sector. All these strategies may be observed in the Scandinavian countries in the latter years. What are the experiences, and to what extent may they be generalized? PMID- 8202737 TI - Pathways to care for the elderly in Greece. AB - The findings from this study show the use of the Emergency Department of a central Athens hospital in 1988 by over 70 year olds. Interviews with staff illustrated varying perceptions of their role in relation to the elderly, associated with occupation and specialty. Findings from interviews with 100 subjects and accompanying persons using the service investigated the circumstances surrounding the attendance at the hospital emergency department and the role of the family in decision making and support. Interviews with a selected subsample of 12 frail elderly people with complex health and socio-economic problems and/or their carers illustrated the lack of alternative social and medical support services leading to inappropriate hospital usage, to difficulties and dilemmas for family carers and inadequate care for the isolated elderly. PMID- 8202738 TI - British home and community care: research-based critiques and the challenge of the new policy. AB - The policy of the British central government is among the most coherent and pervasive of those in countries at the leading edge of reform. One perspective is its attempt to match resources to needs. Starting from a summary of the official statement of the logic of the policy and the way in which it reflected policy critiques of the previous decade in Section 1, Section 2 reviews the propositions of the arguments of the mid-1980s in the light of results of research on the nature and causes of patterns of resources, needs and outcomes and their interrelationships, particularly the results of a stream of 'production of welfare' studies focused on who gets what resources and with what effects. Evidence shows that applying some of the assumptions of the new policy dramatically changes the basis for judging the degree to which a cost-effective targeting of resources to needs could in principle be accomplished within the then level of public funding of the services. It shows a higher degree of consistency of allocations than some of the criticisms had implied, but the evidence did not allow a rejection of the proposition that allocations were biased against some kinds of potential beneficiary. Discussing the proposition that community-based services had a low impact on the probabilities of unwanted and inappropriate admission to institutions for long-term care, the evidence shows that low proportions of recipients were subsequently admitted; that as a consequence of assumptions and processes which have been extensively researched, the cost of care in the community approached cost of care in institutions for too few persons for the resources to have been most effectively used to make admission unnecessary, so that resources have not been focused on those for whom the impact is greatest; that generally, providing more rather than less service tended to have a small impact on the probability of admission to institutions. Section 3 discusses what changes in the relations between resources needs and outcomes will be necessary, and what the results of evaluated new models suggest about how to achieve them, discussing the improvement of targeting and increasing the impact of resources on outcomes in the context of the logic and results of care management experiments in the U.K., the U.S.A. and elsewhere, concluding that there is a need to adopt longer time horizons in the implementation of the new policy. PMID- 8202739 TI - Longitudinal patterns of formal and informal social support in an urban elderly population. AB - Stability and change in the use of formal and informal social support was assessed over a three year period among a representative sample of 1855 elderly urban participants in a longitudinal study of aging and health. Whether people received informal, formal, both types of support or no support was determined in baseline, 12 and 24 month personal interviews. Most respondents retained the same form of support across all three interviews. The extent of stability or change varied according to the form of support reported at baseline. Two-thirds of those with no social support continued without support and 40% of those using both informal and formal support continued to do so at subsequent assessments. The substitution of formal for informal support was infrequent and not statistically significant. Pair wise discriminant function analyses of groups of respondents with the most frequent longitudinal support patterns were performed to identify baseline health and social characteristics associated with stable use, the addition of another form of support or change to nonuse, over time. Changes in the use of support were influenced more by initial levels of health and functional status than by social and economic circumstances. Larger proportions of respondents dropped use of support then added an additional form of support. Respondents using both formal and informal support at baseline died across time in higher proportions than those in other support categories. The extent of stability in support use and nonuse, the character of changes in support use across time and greater attrition among those who were the heaviest users of support, serve to create a relative balance in the use of informal and formal support in this aging cohort, at least over the time frame over which respondents were followed in this study. PMID- 8202740 TI - Unmet need among disabled elders: a problem in access to community long term care? AB - To more completely understand unmet need as an indicator of demand for long-term care, longitudinal data on a representative sample of disabled elders were used to track the extent, type, and predictors of unmet need(s) over a 4-year period. Unmet IADL needs were more common than unmet PADL needs with only 1-2% reporting both types. Unmet needs appear to be temporary rather than persistent and are predicted by lack of an engaged (not necessarily unavailable) caregiving system. The data suggest that the rate of unmet personal care need rather than the rate of any unmet need represents a more accurate estimate of the number of elders for whom community long-term care services are critical to decrease risk of institutionalization. PMID- 8202741 TI - Dynamics of functional impairment in late adulthood. AB - The inconclusive debate about Fries' theory of "natural death and the compression of morbidity" has diverted attention from two key issues--the modifiability and related dynamics of functional impairment in late adulthood. Evidence is presented from a large (N = 11,000) panel of adults aged initially 58-63 over the period of a decade which documents substantial modification of functional status. Further, patterned changes in functional status are related to the dynamics of income, historically a major determinant of functional status, and independently to educational attainment. The dynamics of functional status, of income, and of their relationship are explored using discrete time hazard models in an event history analysis incorporating time-varying income and functional status indicators. The importance of income and of education as positive, independent predictors of functional status and patterned changes of functional status is confirmed. The implications of this finding for differentiating distal (e.g. education) and proximate (e.g. income) measures of socioeconomic status and for assessing competing theories of social causation and social selection are discussed. PMID- 8202742 TI - How measurement techniques influence estimates of disability in older populations. AB - Measures of disability in activities of daily living (ADL) have become important indicators of the health of older persons. One fundamental decision in disability research is constructing or choosing a rating scale to measure ADL disability. Although there is growing consensus in the field on what ADLs to measure, there is little agreement on how to measure ADL disability. This study compares the effect of scales that rate the presence of difficulty, use or human assistance and use of any type of assistance to perform seven different ADLs on prevalence estimates of disability in a probability sample of 1818 adults 70 years of age and older living in the six New England states. Results reveal that different disability rating scales can have a dramatic impact on prevalence estimates of disability in older populations. Measures that used the 'difficulty' scale produced disability estimates from 1.2 to 5 times greater than estimates from the 'human assistance' scale. The effect of rating scales was associated with respondents' age, social factors, and health status. Effects also varied substantially across different ADLs. Researchers need to make careful choices of the disability ratings scales and use caution in drawing inter-study comparisons where different scaling methods were employed. PMID- 8202744 TI - Tolerating reality: the experience of parents of HIV positive sons. AB - In this study, the experience of parents as they discover that their son is HIV+ or has AIDS, witness their deterioration and death, is described. Using the methods of grounded theory, 13 parents (8 mothers and 5 fathers) were interviewed and a model depicting the basic social psychological process (BSSP), keeping reality at a tolerable level, was developed. Six stages of tolerating reality are: Suspecting, Taking it in, Going along with the changed reality, Being swept along with symptoms, Beating down the denial, and learning to live with it. Parents engaged in a number of strategies aimed at keeping reality at a tolerable level, so they could function in their 'comfort zone' and cope with day-to-day horror, fear and uncertainty while attending to their son. PMID- 8202743 TI - Does intergenerational social support influence the psychological well-being of older parents? The contingencies of declining health and widowhood. AB - This study investigates whether social support from adult children improves the psychological well-being of elderly parents. Support is studied as a direct influence on emotional distress and as a moderator of the distressing consequences of health problems and widowhood. Research questions are addressed using data from elderly parents participating in 1985 and 1988 surveys of the U.S.C., Longitudinal Study of Three Generation Families. Results from multiple regression analyses indicate that instrumental and expressive forms of social support are weakly related to 3-year change in positive and negative aspects of psychological well-being. However, both types of support moderate declines in well-being associated with poor health and widowhood. We conclude that the psychological benefits of intergenerational social support are contingent on the vulnerability of the older parent, when expectations for assistance are at their greatest. This finding has considerable implications for family theory and policy. PMID- 8202745 TI - Mothers' perceptions of severe pneumonia in their own children: a controlled study in Pakistan. AB - In 1992, 320 mothers were interviewed in a Rawalpindi hospital to identify which of the signs and symptoms they saw in their own children were most consistently linked with a clinical diagnosis of pneumonia as opposed to common cold. A related goal was to determine whether mothers could correctly judge the actual presence or absence of two major pneumonia signs--fast breathing and chest indrawing. The mothers were predominantly poor and 43% were illiterate. The study sample was composed of four matched groups: (1) mothers of 80 children with pneumonia, most with severe disease, interviewed after the child was referred to the ward; (2) mothers of 80 such children interviewed in the outpatient clinic prior to any discussion of the pneumonia diagnosis; (3) mothers of 80 children with common cold; and (4) mothers of 80 'well' children. Results showed that when mothers were interviewed in the clinic, their perception that a child had fast breathing and/or chest indrawing was highly correlated with pneumonia (sensitivity 64%, specificity 90%). Mothers were even more likely to say that a child had these signs after the pneumonia diagnosis had been conveyed, suggesting that interaction with doctors influenced their views. Fast breathing was better recognized than chest indrawing, and accurate diagnosis of both signs was better among mothers having prior experience with childhood pneumonia. The data suggest that even in the absence of formal ARI education, a majority of Pakistani mothers attending hospitals in indigent areas can recognize these two signs in their own children. However, the seriousness of the signs and their connection with pneumonia should be stressed in education campaigns since a high percentage of children had chest indrawing (a late sign of severe disease) by the time they were brought to the hospital. PMID- 8202746 TI - Susto and the career path of the victim of an industrial accident: a sociological case study. AB - This is a case study of the processes involved in attaining the status of 'victim' after an industrial accident. In this case a migrant working in the manufacturing industry becomes increasingly 'disabled' and seeks legitimation as a 'victim' who is 'worthy' of financial compensation. The institutional processes involved are the industrial, medical and legal systems. Chronic pain is a condition that often defies an unambiguous diagnosis. Most chronic pain victims are therefore constantly seeking legitimation for their condition as physicians attempt to uncover the aetiology of the pain. Most chronic pain victims also fail to fulfil the expectation of getting well as soon as possible. Physicians can, at best, only give a prognosis that is little better than an 'educated guess'. The conditional nature of the legitimacy gives the chronic pain victims only limited legitimacy for their sick role and this often results in physicians seeking psychological or moral explanations for what began as a relatively simple physical problem. Psychological or psychiatric diagnoses are considerably weaker metaphorically than physiological diagnoses and tend to infer the strong possibility of the victim contributing to her/his condition as a result of hypochondriacal or psychosomatic 'tendencies' or, even worse, 'malingering'. The migrant client can exacerbate this situation through an earnest desire to (over)conform to norms by going along with whatever is recommended by people who hold superior status by virtue of their knowledge and power ('posicion'). Among some Latin American countries 'over-compliance' has been recognised a socio medical condition and is termed 'susto'. In the workers' compensation context the shift to overconformity ('susto') results from the uncertainty about receiving (legitimate) acknowledgement and compensation. The desire is to ensure, as far as possible, that a certainty of outcome is achieved (i.e. a return to work or adequate compensation). In other words, concurrent practises within the system (medical-social-legal) produces what it tries to eliminate--the seemingly unjustifiable/illegitimate internalising of the role of victim intent on receiving compensation. 'Susto' is therefore an adaptive response to normative ambiguity and uncertainty about future outcomes. Under conditions of worsening health (physical and mental), and the pressure to continue treatment, the best "solution" for the victim appears to be to "pull the victim out of the medical system", to de-socialise her/him from semi-institutionalisation, and to use social and informal support structures to build up on the victim's independence, self-esteem, personal integrity and sense of control of her/his own life. PMID- 8202747 TI - The social significance of routine health behavior in Tamang daily life. AB - Programs to promote behavioral change among non-Western people sometimes emphasize individual cognitive processes at the expense of social practices. While health beliefs are important, it is equally important to understand the language and the pattern of relationships that affect routine health behaviors. In rural central Nepal we conducted a health survey of 265 Tamang people, followed by a series of 22 in-depth interviews focused on diarrhea and related illnesses. This paper describes the nomenclature used and automatic health behaviors enacted, in response to diarrheal illnesses in Tamang villages. We draw on the work of Anthony Giddens to show that routine health behavior is embedded in specific social relationships that in turn help to structure many aspects of Tamang daily life. We discuss the significance of routine Tamang health behavior in light of oral rehydration therapy programs. PMID- 8202749 TI - [Sheltered workshops ten years later]. PMID- 8202748 TI - [Halfway houses]. PMID- 8202751 TI - [Alternatives to hospitalization]. PMID- 8202750 TI - [Guidance service and after care]. PMID- 8202752 TI - [Vacation]. PMID- 8202753 TI - [Specialized family placement for adults]. PMID- 8202754 TI - [Nursing practice in family therapy admission]. PMID- 8202755 TI - [Constraint and therapeutic space]. PMID- 8202756 TI - [Alternatives to hospitalization]. PMID- 8202757 TI - [The depressed aged person and the community mental health nurse]. PMID- 8202758 TI - [Reflections on the work of home visits]. PMID- 8202759 TI - [Deceit in the search for a need]. PMID- 8202760 TI - [Learning to retake charge]. PMID- 8202761 TI - [Let me die in peace]. PMID- 8202762 TI - [Returning the patient to his town, in his neighborhood]. PMID- 8202763 TI - [Night hospitalization in psychiatry]. PMID- 8202764 TI - Snake venom poisoning in the United States: a review of therapeutic practice. AB - Snake venom poisoning constitutes a medical emergency. It is a complex type of poisoning that not only affects the local bite site but may involve multiple organ systems as well. In the United States, poisonous snakes account for approximately 8,000 bites annually, resulting in about 9 to 15 fatalities. The majority of deaths occur in children, the elderly, and untreated or mistreated individuals. Pit vipers account for almost all bites. Diagnosis and treatment are based on clinical signs and symptoms of envenomation along with identification of the snake. First aid treatment should focus on transporting the victim to the nearest medical facility as soon as possible. Previously advocated first aid measures such as tourniquet, incision and suction, cryotherapy, and electric shock should be avoided. The mainstay of treatment for envenomation is the prompt administration of sufficient quantities of the appropriate antivenin. PMID- 8202765 TI - Sarcoidosis and ELISA for Borrelia burgdorferi. AB - Lyme disease can be confirmed by detection of IgM and IgG antibodies against the causative pathogen Borrelia burgdorferi. Enzyme-linked immunosorbent assay (ELISA) can be confirmatory within weeks of symptom onset. Sarcoidosis has not previously been reported as one of the disease processes associated with a false positive ELISA for Lyme disease. In our study, Lyme ELISA was obtained in 25 patients with various degrees of activity of sarcoidosis. ELISA was positive for Lyme disease in only one of these patients. Sarcoidosis may not be one of the diseases that commonly results in a false-positive Lyme ELISA. PMID- 8202766 TI - Laparoscopic appendectomy, is it worth it? AB - The recent experience with open appendectomy was compared to our initial experience with laparoscopic appendectomy. Thirty-eight patients had open appendectomy for acute appendicitis. Two major and four minor complications occurred. Concurrently, 39 patients had laparoscopic appendectomy. There was one major and one minor complication. Of the laparoscopic patients, 69% received less than 24 hours of parenteral postoperative analgesia, compared to 44% of the patients in the open group. Fifteen of 39 laparoscopic patients (38%) were discharged within 24 hours of operation versus 3 of 38 (8%) in the open group. Total mean hospital cost for the laparoscopic group, $7,500, was significantly greater than for the open group, $5,700, because of increased laparoscopic equipment charges. Both open and laparoscopic appendectomy procedures were performed with minimal morbidity. The benefits of laparoscopy were earlier hospital discharge and less parenteral analgesic use, but it was significantly more expensive. PMID- 8202767 TI - The geography of AIDS: patterns of urban and rural migration. AB - We sought to describe the migration patterns of patients infected with the human immunodeficiency virus (HIV) who seek health services in North Carolina. Of 390 consecutive adult patients with HIV seen at one tertiary care medical center in the southeastern United States in the summer of 1990, 340 (87%) were approached, and 325 (83%) completed surveys. Thirty-seven percent of respondents thought they had been infected and 20% were told they were infected with HIV while living outside of North Carolina. One in five patients thought they had been infected while living in a rural county and more than half now live in rural communities (population of < 50,000). Sixty percent of patients had moved to North Carolina since 1980; 61% of these were North Carolina natives. Injecting drug users were more likely than those with other modes of exposure to HIV to have been diagnosed with HIV infection out of state (34% vs 18%). Patients' reasons for moving to North Carolina included social support (88%), health reasons (54%), and better work/educational opportunities (52%). We found that most patients with HIV who seek health care services in North Carolina live in rural areas with their families, and a substantial proportion migrated in after they were diagnosed out of state. Characterizing these migration patterns is crucial for predicting the diffusion of HIV to rural areas; designing AIDS prevention strategies, education, and health service needs; and assessing federal HIV care funding policies. PMID- 8202768 TI - Tobacco use among American adolescents: geographic and demographic variations. AB - A previous national study indicated that the South dominated other regions of the United States in tobacco use. Using the results of the Teenage Attitudes and Practices Survey conducted by the National Center for Health Statistics, we examined the geographic and demographic differences of tobacco use among US adolescents. The sample consisted of teenagers in grades 7 through 12 nationwide (N = 6,599). Data were collected through telephone interviewing. The variables included demographics and measures of smoking or use of smokeless tobacco (chewing tobacco/snuff). Results indicated that the overall prevalence rate for smokeless tobacco use was 4.44%, but in the South it was 6.38%. The overall smoking prevalence rate was 13.31%, with no substantial difference among regions. Demographic variables such as sex, ethnicity, education, and poverty levels were also related to tobacco use prevalence. These geographic and demographic variations in tobacco use help target specific regions and populations in greatest need of intervention programs. PMID- 8202770 TI - Characteristics of severe hypoglycemia in the patient with insulin-dependent diabetes. AB - To avoid, delay, or ameliorate the microvascular complications of diabetes, intensive insulin therapy with the goal of normoglycemia is required. In most patients with insulin-dependent diabetes mellitus (IDDM), this cannot be achieved because of severe hypoglycemia, which is one of the major causes of morbidity in diabetic patients. To assess the frequency and characteristics of severe hypoglycemia in a single diabetologist's practice, we surveyed 211 consecutive patients with IDDM for a history of severe hypoglycemia (SH), defined as events requiring the assistance of another person. Of these 211 patients, 135 (64%) had at some time had SH. Those with SH had a longer duration of IDDM, currently took more insulin injections, had a higher prevalence of neuropathy and nephropathy, and were less likely to be using human insulin. No difference was found in age, average glycosylated hemoglobin level, frequency of home glucose monitoring, or presence of retinopathy. Half of the patients with SH had confusion and were treated with glucose orally. The remainder were in coma and received i.v. glucose or IM glucagon. Perceived causes of SH were lack of food, excessive insulin, and unusual exercise. We conclude that the frequency of SH is underestimated in clinical practice. Risk factors for SH are longer duration of IDDM, presence of neuropathy and nephropathy, and use of animal insulin. Better education in avoidance and treatment of SH would reduce the morbidity of SH. PMID- 8202769 TI - Desmopressin acetate in cardiac surgery: a double-blind, randomized study. AB - Use of desmopressin acetate (DDAVP) for patients having cardiac surgery is controversial. We did a double-blind, randomized study of 83 patients having cardiac operations at Georgetown University Hospital. The effect of DDAVP on bleeding as compared to placebo was evaluated by blood loss, replacement volume, and laboratory tests. There were no significant differences in baseline and intraoperative data between the DDAVP (n = 40) and placebo (n = 43) groups. Total drainage for the first 24 postoperative hours was 1,214 mL (+/- 78) for the DDAVP group and 1,386 mL (+/- 116) for the placebo group (not significant). There were no significant differences in replacement therapy. In this study, administration of DDAVP did not decrease bleeding. PMID- 8202772 TI - CT findings of hypoxic basal ganglia damage. AB - The outcome of hypoxic ischemic injury ranges from complete recovery to a persistent vegetative state or death, depending on the length of time the patient remains unconscious and the degree of associated cardiac failure. We describe three patients who were comatose from a hypoxic and/or ischemic injury and whose principal computed tomographic (CT) finding was bilateral basal ganglia hypodensities. Two of these patients were discharged from the hospital with minimal residual neurologic deficits. These cases and review of the literature suggest that ischemic basal ganglia signs on CT scan are not necessarily a predictor of severe neurologic sequelae. PMID- 8202771 TI - Incidence of cervical spine injury in patients with gunshot wounds to the head. AB - Cervical spine immobilization is standard during the early stages of prehospital and hospital care of patients with blunt head injury. However, the need for cervical spine immobilization in patients with gunshot wounds to the head has not been addressed. To determine the incidence and types of cervical spine injury in this group, we retrospectively examined the records of 308 consecutive patients who had computed tomographic (CT) scans of the head to evaluate brain injury after gunshot wounds. Of the 266 patients with data adequate for review, 157 (59%) had a complete lateral x-ray film of the cervical spine. Of these 157, 105 had wounds limited to the calvaria, and none had cervical spine injury. Of 52 patients with complete lateral x-ray films and wounds not limited to the calvaria, 5 (10%) had cervical spine or spinal cord injury. Of the 192 patients who had CT-proven intracranial injury, 86 (45%) required immediate intubation before x-ray films were obtained, and 67 (35%) died. We conclude that cervical spine immobilization may not be required during endotracheal intubation of brain injured gunshot victims with wounds limited to the calvaria. PMID- 8202773 TI - Fluoroscopic evaluation of the ureters during intravenous urography. AB - In a prospective study, we assessed the usefulness of fluoroscopy in visualizing the ureters during intravenous urography. The percentage of ureter visualized was compared on radiographs acquired with and without fluoroscopic guidance. The length of ureter shown was significantly greater with fluoroscopic spot filming than with traditional urography. We recommend adjunctive fluoroscopy to enhance ureteral visualization during intravenous urography. PMID- 8202774 TI - Medicine residents' practices in cancer screening in a Hispanic population. AB - Cancer screening is a valuable intervention to reduce breast cancer mortality and the incidence of invasive cervical carcinoma. We conducted a retrospective survey to determine the residents' compliance with use of mammography and Pap smear in Hispanic women. A total of 280 charts that met the inclusion criteria were reviewed. According to the guidelines, 784 mammograms and 714 Pap smears were indicated. The residents' compliance with mammography was 10.6% (+/- 9.16) and with Pap smear, 6.6% (+/- 7.68). The study demonstrates an unacceptable level of cancer screening practice by the medicine residents caring for this Hispanic population. PMID- 8202775 TI - Noncompliance of high-risk pregnant women in keeping appointments at an obstetric complications clinic. AB - We conducted this survey to determine reasons for missed appointments and the relationship between missed appointments, knowledge of diagnosis, and perception of the impact of this diagnosis on pregnancy outcome. We attempted to interview, by telephone, 506 women within 24 hours of their missing an appointment at a high risk obstetric clinic. Information from 118 respondents was analyzed. The study population was 71% black and 29% white, the average age was 23, and both income and educational levels were low. Seventy-three percent of the women know their medical diagnosis, yet only 30% perceived the problem as a threat. Women who could identify their diagnosis were more likely to evaluate prenatal care positively (P < .006). Women who perceived their condition as a threat seemed to blame lack of transportation less often as a reason for missing an appointment. Many women who missed appointments did not know why they were being seen, and many did not perceive that the care was useful. Effective patient education could improve compliance. PMID- 8202776 TI - Preconception evaluation and intervention. AB - Many pregnancies are predisposed to complications by events that occur in the first weeks of gestation. In fact, these complications may occur prior to the time that a woman knows she has become pregnant. Preconception care offers patients the opportunity to address these conditions before conception; the potential for a satisfactory pregnancy outcome is thereby increased. In the following report, I summarize current understandings in preconception care. Recent advances in preconception care have expanded the opportunities for preventing adverse reproductive outcome. Although the study of preconception care is a relatively new innovation, recent studies have shown the value of preconception intervention. PMID- 8202777 TI - Mediastinal lung cancer: answers and questions. AB - A literature review was done to define the relative roles of radiation and surgery in the treatment of mediastinal stage III, non-small-cell lung cancer with no distant metastasis. No two reports are comparable. Little information is available on the clinical, preoperative stage as it relates to surgical findings and to survival. Rationale for adjuvant radiation is lacking from the reports. There is no survival advantage of surgery, even with postoperative radiation, over radiation alone for clinical stage III disease. Patients whose cancer seems early stage but is found to be pathologic stage III at time of surgery may benefit from the combination therapy, although this is controversial. Treatment failure is usually systemic, so there is a strong argument for adjuvant chemotherapy as well. Uniform multimodality reporting of results is necessary so that the appropriate roles of surgery, radiation, and chemotherapy can be identified for this group of patients. PMID- 8202778 TI - Cementifying fibroma: resection of recurrent mandibular lesion with microsurgical preservation of inferior alveolar nerve and immediate reconstruction. AB - Cementifying fibroma is a benign fibro-osseous lesion that may occur in either the mandible or the maxilla, with a predilection for the mandible. In the patient described, a recurrent mandibular cementifying fibroma was successfully resected, with microsurgical preservation of the inferior alveolar nerve and immediate reconstruction via an autogenous iliac bone graft. PMID- 8202779 TI - Toxoplasma gondii pneumonia in patients with the acquired immunodeficiency syndrome: diagnosis by bronchoalveolar lavage. AB - We describe the cases of two individuals with advanced AIDS who sought treatment for rapidly progressive respiratory failure due to T gondii pneumonia. The first patient responded to specific therapy after an early diagnosis but died 2 months later of bacterial sepsis. In the second case, the diagnosis was made at autopsy. This led to a meticulous retrospective review of the original slides of material obtained from BAL. T gondii tachyzoites not previously identified during the initial analysis of the slides were seen on both GIE and PAP stains. Neither of our severely immunocompromised patients had evidence of central nervous system involvement. Even though we cannot exclude dissemination to other organs, a progressive pneumonitis mimicking a classic P carinii infection was the primary presentation. Trophozoites were identified by BAL in both cases, underscoring the diagnostic potential of this minimally invasive procedure. PMID- 8202780 TI - Unilateral adrenal hyperplasia. AB - A case of unilateral primary adrenal hyperplasia, without concomitant hypokalemia, is presented. After surgical removal of the gland, a complete remission occurred. This rare condition may, in fact, be more frequent than thought as it can coexist with normokalemia. We postulate that it is probably a new phase of the transformation between hyperplasia and adenomas that can also occur in the adrenal cortex similar to such transformations in other endocrine organs. PMID- 8202781 TI - Group G streptococcal bacteremia caused by an asymptomatic esophageal carcinoma in an elderly man. AB - I describe the case of a 70-year-old man with group G streptococcal bacteremia, anemia, and stools positive for occult blood in whom no clear source of infection was found until an asymptomatic esophageal carcinoma was diagnosed. Group G bacteremia has been associated with neoplastic sources. Although this patient was asymptomatic--even after a retrospective review of symptoms--endoscopy would still have been done because the stools were positive for occult blood. However, it is well known that bleeding from cancers is often intermittent and that stools may have to be tested on multiple occasions before bleeding is seen. This case supports the association of group G streptococcus and malignancy and suggests that patients with streptococcal group G bacteremia of no obvious source should have a workup for occult malignancy even in the absence of other indications. PMID- 8202782 TI - Massive upper gastrointestinal bleeding due to Candida esophagitis. AB - Significant hemorrhage from esophageal candidiasis in patients without a major bleeding diathesis is extremely uncommon. A case of recurrent, severe upper gastrointestinal bleeding due to hemorrhagic candidal esophagitis in a man with renal failure is described. Dysphagia, odynophagia, and retrosternal chest discomfort were all absent. Oral thrush was present only at the outset. Standard therapy for massive bleeding with blood products alone was not successful. Intravenous amphotericin eventually resulted in resolution. PMID- 8202783 TI - Pernicious anemia manifesting as angina pectoris. AB - Here we describe a case of angina pectoris in a patient for whom an extensive cardiovascular workup was done, with negative results. Eventually, the cause of his symptoms was found to be pernicious anemia. Although angina is an uncommon manifestation of pernicious anemia, a review of the literature suggests that the correlation between anemia and angina has been well described. Our case highlights an important differential diagnosis to consider for patients with exercise-induced chest pain and serves to emphasize the attention that should be focused on simple screening laboratory studies. The emphasis in this case is the sequence in which the studies are done. A simple complete blood count with proper interpretation and intervention at the outset of evaluation could possibly have prevented a number of unnecessary, invasive, and costly studies. PMID- 8202784 TI - Snake bites. PMID- 8202785 TI - Childhood sexual abuse. PMID- 8202786 TI - Recognizing delirium in patients with psychiatric symptoms. PMID- 8202787 TI - Don't overlook small intestinal endoscopy for evaluating gastrointestinal bleeding of obscure origin. PMID- 8202788 TI - The effects of aerobic exercise after lumbar microdiscectomy. AB - STUDY DESIGN: This study determined whether lumbar discectomy patients could endure an aerobic exercise program sufficient to achieve a training effect, and whether any functional advantages were derived. METHODS: Trained volunteers (n = 19) were compared with untrained control subjects (n = 18) after a 12-week aerobic and rehabilitation exercise program. Subjects completed a maximal graded exercise test, a hydrostatic weighing test, and a battery of self-report inventories. RESULTS: Using a discriminant analysis, as a post hoc test, maximal oxygen consumption was found to be the factor responsible for the difference between the groups (P < 0.006). CONCLUSION: Oxygen consumption was more than three times as important as any other single variable in differentiating between the groups. PMID- 8202789 TI - Evaluation of serum osteoblast mitogenic activity in spinal cord and head injury patients with acute heterotopic ossification. AB - STUDY DESIGN: This was a blind, prospective study of the effect of sera from patients with spinal cord and head injuries on osteoblast proliferation. OBJECTIVES: The authors studied whether a humoral factor that stimulates the formation of heterotopic bone is released into the circulation after a neural injury. BACKGROUND DATA: Other authors have shown that a humoral osteoinductive factor may be released after head and spinal cord injuries. METHODS: Serum was obtained at certain times throughout the first 12 weeks post-injury and from control subjects. It was incubated with osteoblasts harvested from fetal rats, as well as with fibroblast controls. RESULTS: There was a significant rise in serum mitogenic activity after injury in both groups. When patients that developed heterotopic ossification were compared to other patients and controls, no significant differences were seen. CONCLUSIONS: This in vitro study fails to support a humoral mechanism for heterotopic ossification after spinal cord or brain injuries. PMID- 8202790 TI - The osteogenic potential of rib autografts can be preserved in culture. AB - STUDY DESIGN: This was an experimental study to compare various methods of storing rib autograft between stages of spinal surgery. OBJECTIVE: The authors' goal was to determine the optimum conditions for storing bone graft, while preserving its osteogenic potential. SUMMARY OF BACKGROUND DATA: It never has been demonstrated that osteoblastic function can be preserved after bone graft is stored. Other researchers have shown preservation of cellular function, but not its nature. METHODS: Excised rib was stored in one of several ways: in culture medium at -196 C, 4 C, or 37 C, or in saline at 4 C for 2 weeks and then cultured at 37 C. Any cells produced were characterized using standard techniques. RESULTS: Bone stored at 37 C and -196 C retained its osteogenic potential. Bone stored at 4 C in saline did not. Bone stored at 4 C in culture medium was intermediate in its preservation of osteogenic capacity. CONCLUSIONS: Bone stored under suitable conditions retains osteogenic potential, and when reimplanted will add osteogenic cells to the fusion mass. PMID- 8202791 TI - A male incumbent worker industrial database. Part I: Lumbar spinal physical capacity. AB - STUDY DESIGN: A group of 160 incumbent male railroad workers volunteered for a study of lumbar spine physical capacity. METHODS: They were initially subjected to inclinometric measurements of sagittal and coronal regional mobility (T12-S1). They also were tested on isokinetic trunk strength measurement devices for sagittal (bending) and axial (twisting) trunk strength at multiple speeds. RESULTS: Results showed that they demonstrated mild deficits of lumbar sagittal extension mobility, trunk extensor strength, and sagittal/axial high speed (150 180 degrees/sec) trunk strength when compared with population averages from a previously derived normative database of a nonhomogeneous male population (matched for age and body weight). CONCLUSIONS: It was hypothesized that instructions about "correct lifting techniques," uniformly provided to these workers, may have resulted in an unintended decrement in trunk mobility and strength. PMID- 8202792 TI - A male incumbent worker industrial database. Part II: Cervical spinal physical capacity. AB - STUDY DESIGN: Quantified cervical physical examination data are provided for a group of 160 incumbent railroad workers from four laboring crafts. OBJECTIVES: The subjects were tested for cervical mobility and strength, according to standardized protocols as part of a comprehensive physical examination and functional testing procedure to establish normative data associated with the axial musculoskeletal system. RESULTS: Tri-planar cervical inclinometric mobility norms are provided, as are sagittal and coronal isometric cervical strength data. PMID- 8202793 TI - A male incumbent worker industrial database. Part III: Lumbar/cervical functional testing. AB - STUDY DESIGN: A group of 160 incumbent male railroad workers was administered a battery of isokinetic and isoinertial lumbar/cervical lifting tests that served as a paradigm for whole-person functional testing of manual handling tasks. RESULTS: Results demonstrated that the workers' performance was near normal or somewhat above population averages according to previously derived heterogeneous normative samples. However, there were some differences among the four laboring crafts that made up the present incumbent worker sample. CONCLUSIONS: The implications of these differences are discussed. PMID- 8202794 TI - Trunk muscle activation. The effects of torso flexion, moment direction, and moment magnitude. AB - OBJECTIVES: This study was performed to quantify the electromyographic trunk muscle activities in response to variations in moment magnitude and direction while in forward-flexed postures. METHODS: Recordings were made over eight trunk muscles in 19 subjects who maintained forward-flexed postures of 30 degrees and 60 degrees. In each of the two flexed postures, external moments of 20 Nm and 40 Nm were applied via a chest harness. The moment directions were varied in seven 30 degrees increments to a subject's right side, such that the direction of the applied load ranged from the upper body's anterior midsagittal plane (0 degree) to the posterior midsagittal plane (180 degrees). RESULTS: Statistical analyses yielded significant moment magnitude by moment-direction interaction effects for the EMG output from six of the eight muscles. Trunk flexion by moment-direction interactions were observed in the responses from three muscles. CONCLUSIONS: In general, the primary muscle supporting the torso and the applied load was the contralateral (left) erector spinae. The level of electromyographic activity in the anterior muscles was quite low, even with the posterior moment directions. PMID- 8202795 TI - Comparison of lumbar range of motion using three measurement devices in patients with chronic low back pain. AB - STUDY DESIGN: A correlational design was used to compare the lumbar spine's total sagittal range of motion (ROM) within a chronic low back pain patient population (n = 42) using three different measurement systems. OBJECTIVES: To compare, within a back pain patient population, the relationship of ROM measurements obtained from a motion analysis system (SPINETRAK), a lumbar extension rehabilitation device (MedX), and liquid inclinometers. METHODS: Total lumbar sagittal ROM was determined with each device in each subject as part of patients' standard clinical evaluation. RESULTS: Results indicated that the motion analysis system is significantly correlated with the liquid inclinometers and mildly correlated with the MedX. Inclinometer and MedX ROM measurements are also significantly correlated. To assess individual differences, dependent t tests were performed. Results indicated that the SPINETRAK yielded significantly lower ROM than the inclinometer or the MedX. The MedX and inclinometer measures did not significantly differ. CONCLUSIONS: This report shows that, depending on the device and procedures used, the lumbar sagittal ROM within a chronic low back pain population vary significantly. PMID- 8202796 TI - Cyclic compression-flexion loading of the human lumbar spine. AB - STUDY DESIGN: The present study was designed to investigate the biomechanical behavior of the lumbar spine under controlled complex physiologic situations with chronic input. OBJECTIVE: The objective was to determine the response of the human cadaver lumbar spinal column under repetitive compression-flexion forces. SUMMARY OF BACKGROUND DATA: Studies have been conducted in the past to determine the biomechanical response of the spine under uniaxial or pure forces. There is no methodology that can be used to apply and continuously quantify the fatigue response of the lumbar spinal column under controlled combined complex loading vectors (e.g., compression flexion). METHODS: Intact cadaver lumbar columns (L1 L5) were mounted with the superior end in contact with a ball-transfer mount, inducing a flexion load to the spine while allowing multiple degrees of freedom. The distal portion of the specimen was attached to a six-axis load cell to quantify the force sustained by the specimen during the entire loading cycle. The applied load and piston deformation and the generalized six-axis force histories were gathered as a function of time using a digital data acquisition system. RESULTS: The stiffness versus number of cycles (K-N) response exhibited nonlinear characteristics. The stiffness increased initially and then stabilized after 1,000-2,000 cycles of loading, delineating the viscoelastic characteristics of the spine. The initial stiffness increase before stabilization was found to be significantly different (P < 0.025) compared to the stiffness beyond 2,000 cycles. CONCLUSIONS: The data suggest that the fatigue response can be understood by cyclically loading the ligamentous lumbar spine preparation to approximately 2,000 cycles. PMID- 8202797 TI - The treatment of lumbar spinal pain syndromes diagnosed by discography. Lumbar arthrodesis. AB - STUDY DESIGN: This retrospective review of patients whose discogenic pain syndromes were treated by lumbar arthrodesis was designed to examine the clinical efficacy of this diagnostic modality and analyze possible confounding variables. OBJECTIVES: Clinical outcome was examined with respect to status of the arthrodesis, discographic diagnosis, and demographic variables. SUMMARY OF BACKGROUND DATA: Discography continues to be a controversial diagnostic technique for spinal pain syndromes. The morphologic information provided by discography is well known. However, disagreement exists concerning the clinical utility of the pain provoked by this modality. METHODS: Forty-eight patients were included in this study. In all patients, the chief complaint was low back pain. In all patients, the definitive diagnostic technique was lumbar discography followed by computerized tomographic scanning. All patients underwent lumbar arthrodesis. Data were collected in four categories: 1) demographic characteristics, 2) physical findings, 3) results of diagnostic studies, and 4) characteristics of surgical procedures. Data from these categories were studied with respect to clinical rating and status of the arthrodesis. RESULTS: Overall, 46% were judged to have a satisfactory clinical outcome at final follow-up. Forty-eight percent were judged to have a solid arthrodesis. CONCLUSIONS: Based on the results of this study, it appears that discogenic pain syndromes can be treated by arthrodesis. PMID- 8202798 TI - The relative contributions of the disc and zygapophyseal joint in chronic low back pain. AB - STUDY DESIGN: A prospective cross-sectional analytic approach was taken. OBJECTIVES: This study sought to determine the relative contribution of the disc and the zygapophyseal joint as a pain source in patients with chronic low back pain. SUMMARY OF BACKGROUND DATA: Previous studies have employed either zygapophyseal joint blocks or discography, but in no studies have both procedures been performed. METHODS: Ninety-two consecutive patients with chronic low back pain were studied using both discography and blocks of the zygapophyseal joints. RESULTS: Thirty-six patients (39%) had at least one positive discogram as defined by exact pain reproduction, an abnormal image, and a negative control. Eight patients responded to both a screening zygapophyseal joint block using lignocaine and a confirmatory block using bupivacaine. Only three patients had both a positive discogram and a symptomatic zygapophyseal joint. CONCLUSIONS: In patients with chronic low back pain, the combination of discogenic pain and zygapophyseal joint pain is uncommon. PMID- 8202799 TI - Thoracic zygapophyseal joint pain patterns. A study in normal volunteers. AB - STUDY DESIGN: Nine asymptomatic volunteers underwent 40 provocative intra articular injections of the thoracic zygapophyseal joints. OBJECTIVE: The purpose of the study was to isolate and stimulate the thoracic zygapophyseal joints via fluoroscopically guided intra-articular injections to determine whether they are potential pain generators. SUMMARY OF BACKGROUND DATA: Experimentally, the cervical and lumbar zygapophyseal joints have been shown to produce pain, and tentative referral patterns have been established. Referral patterns based on stimulation of the thoracic zygapophyseal joints have not been previously reported. METHODS: Four subjects underwent right-sided T3-T4, T5-T6, T7-T8, and T9-T10 joint injections, and four subjects underwent left-sided T4-T5, T6-T7, T8 T9, and T10-T11 joint injections. One subject underwent both the right- and left sided joint injections. The zygapophyseal joints were injected with contrast medium only, and the quality, intensity, and distribution of evoked pain was recorded. RESULTS: In this asymptomatic population, 72.5% of joints injected produced a sensation/pain that was different from the sensation of needle advancement through the soft tissues. In 27.5% of joints injected, there was no evoked pain despite adequate capsular distension. Evoked referral patterns were consistent in all subjects. Significant overlap occurred in the referral patterns, with most thoracic regions sharing 3-5 different joint referral zones. CONCLUSIONS: This study provides preliminary confirmation that the thoracic zygapophyseal joints can cause both local and referred pain. A referral pain diagram has been constructed. PMID- 8202800 TI - Changes in intervertebral disc cross-sectional area with bed rest and space flight. AB - STUDY DESIGN: We measured the cross-sectional area of the intervertebral discs of normal volunteers after an overnight rest; before, during, and after 5 or 17 weeks of bed rest; and before and after 8 days of weightlessness. OBJECTIVES: This study sought to determine the degree of expansion of the lumbar discs resulting from bed rest and space flight. SUMMARY OF BACKGROUND DATA: Weightlessness and bed rest, an analog for weightlessness, reduce the mechanical loading on the musculoskeletal system. When unloaded, intervertebral discs will expand, increasing the nutritional diffusion distance and altering the mechanical properties of the spine. METHODS: Magnetic resonance imaging was used to measure the cross-sectional area and transverse relaxation time (T2) of the intervertebral discs. RESULTS: Overnight or longer bed rest causes expansion of the disc area, which reaches an equilibrium value of about 22% (range 10-40%) above baseline within 4 days. Increases in disc area were associated with modest increases in disc T2. During bed rest, disc height increased approximately 1 mm, about one-half of previous estimates based on body height measurements. After 5 weeks of bed rest, disc area returned to baseline within a few days of ambulation, whereas after 17 weeks, disc area remained above baseline 6 weeks after reambulation. After 8 days of weightlessness, T2, disc area, and lumbar length were not significantly different from baseline values 24 hours after landing. CONCLUSIONS: Significant adaptive changes in the intervertebral discs can be expected during weightlessness. These changes, which are rapidly reversible after short-duration flights, may be an important factor during and after long-duration missions. PMID- 8202801 TI - Low-dose radiography of scoliosis in children. A comparison of methods. AB - STUDY DESIGN: Records of 1,582 conventional and computed radiographic examinations performed to evaluate scoliosis were reviewed and compared to determine differences in total radiation burden. OBJECTIVE: This study evaluated the impact of computed radiographic imaging (CRI) on radiation exposure in children undergoing serial spinal radiographs for scoliosis assessment and compared exposure from CRI with that of low-dose film-screen combinations. SUMMARY OF BACKGROUND DATA: CRI permits diagnostic radiographic studies to be performed with a dose reduction of 80%-95% compared to conventional film-screen systems. High speed film-screen systems also permit a significantly lower exposure. Each approach has unique advantages and disadvantages. METHODS: Over 6 years, we performed 1,582 spinal examinations in children 4-14 years old using reduced dosage techniques with computed radiography. The images were obtained with Fuji FCR 101 and Philips PCR/SP systems. The adequacy of diagnostic image quality in the serial evaluation of scoliosis at different exposure levels was evaluated and compared with regular and film-screen systems with speeds ranging from 250 to 1,200. RESULTS: Diagnostic-quality images for evaluating scoliosis can be obtained with doses of 5% or less than required with conventional film screen systems. Computed radiography provides image quality and dose reduction comparable to a 1,200-speed film-screen system. CONCLUSION: CRI gives satisfactory images at 5% reduction of the standard film-screen dose. Based on comparison with a 1,200 speed film-screen system, CRI provides equal or better image quality at a similar radiation dose. The cost of CRI is higher than for film-screen radiography, but wide latitude and the ability to tailor dose with requirements for image quality are significant advantages for CRI. PMID- 8202802 TI - A computerized technique for analyzing lateral bending behavior of subjects with normal and impaired lumbar spine. A pilot study. AB - STUDY DESIGN: A computerized technique, employing a motion analysis system and a force platform, was developed to analyze lateral bending behavior of subjects with normal and painful spines. METHODS: Lateral bending was quantified using motion (angle and speed of rotation), force (ground reaction kinetics), and biomechanical behavior ("compliance" and "transfer mobility") characteristics of four discrete spinal segments measured during standing, range of bending, and bending at normal and maximum speeds. RESULTS: For subjects with pain, there were reductions in the range of lateral bend (43%) and speed of rotation (39%). Ground reaction moment about the medial-lateral axis was greater (58%), whereas that about the anterior-posterior axis was less (28%). "Compliance" was less (25%), whereas "transfer mobility" was greater (24%). CONCLUSIONS: The findings suggest that the characteristics of lateral bending, rather than range of motion, is most affected in subjects with pain. PMID- 8202803 TI - Prevalence of incidental intraspinal lipoma of the lumbosacral spine as determined by MRI. AB - STUDY DESIGN: The prevalence and appearance on MRI of lipomas of the filum terminale was studied in a random population referred to MRI for evaluation of the lumbosacral spine. The MRI scans of 100 patients selected at random were retrospectively reviewed. OBJECTIVES: The study sought to determine the frequency and MRI appearance of incidental filum lipomas in a random population. SUMMARY OF BACKGROUND DATA: Postmortem studies have reported a 4%-6% incidence of occult fibrolipomas of the filum terminale in what were thought to be otherwise normal spinal cords. The improved resolution of MRI imaging allows the detection of small amounts of fat associated with the filum terminale that heretofore had not been demonstrated on radiologic imaging examinations. METHODS: The lumbosacral spine unenhanced MRI scans of 100 patients not previously operated upon were selected at random and were retrospectively reviewed by two of the authors (EB and JCM). RESULTS: Of the 100 MRI examinations reviewed, four patients were found to have small lipomas of the filum terminale. No spinal dysraphism or cord tethering were present in these four patients. Their clinical symptoms were related to disc herniation in two patients, spinal stenosis in one, and discitis in one. The lipomatous tissue was hyperintense to cerebrospinal fluid (CSF) on T1 weighted images and hypointense to CSF on T2-weighted images. CONCLUSIONS: Incidental lipomas of the filum terminale were present in 4% of 100 lumbosacral spine MRI examinations in a random population. PMID- 8202804 TI - A simple method for diagnosing traumatic occlusion of the vertebral artery at the craniovertebral junction. AB - STUDY DESIGN: A simple method, thin-slice contrast-enhanced computed tomographic (CT) scan, was evaluated as a first-line rapid screening procedure for diagnosing traumatic occlusion of the vertebral artery at the craniovertebral junction. OBJECTIVES: This procedure was performed in patients suffering from injuries of the high cervical spine or the craniovertebral junction. Vertebral angiography was undertaken after this procedure to confirm the diagnosis. SUMMARY OF BACKGROUND DATA: Well-enhanced vertebral arteries can be demonstrated clearly in normal subjects by using this method. Occlusion of the vertebral artery produces delayed contrast enhancement of the proximal artery and abrupt interruption of its course. METHODS: Thin-slice CT scan was performed from the atlas to the occipital condyles after an intravenous injection of angiograffin. The plane of the CT scan was aligned in a parallel manner to the upper margin of the atlas. The CT scanning was repeated until the contrast enhancement of the vertebral arteries became faint. RESULTS: Occlusion of the unilateral vertebral artery was successfully diagnosed in a patient with Jefferson's fracture by using the present technique. A subsequent vertebral angiography confirmed the diagnosis. CONCLUSIONS: The present technique should be performed as a routine screening procedure in patients suffering from injuries to the craniovertebral junction. PMID- 8202805 TI - Internal thoracoplasty. A new procedure. AB - STUDY DESIGN: The efficacy of performing a thoracoplasty from within the thoracotomy during anterior surgery for scoliosis was investigated. OBJECTIVES: Patients were prospectively studied to determine the possible complications and morbidity of the procedure, and were compared to a similar group of patients that previously underwent same-day anterior and posterior procedures for scoliosis, but without thoracoplasty. Description of the technique is presented. SUMMARY OF BACKGROUND DATA: The seven study patients had uneventful intra- and post operative courses. For the posterior procedure (CD instrumentation), only morselized rib graft was used, obviating the need for iliac graft. RESULTS: There was no greater rate or additional types of complications in the study group compared to the control group, except one additional day of thoracotomy tube retention. CONCLUSIONS: When same day anterior and posterior procedures are to be performed for scoliosis, internal thoracoplasty is indicated, as a source of autogenous bone and for cosmesis. PMID- 8202806 TI - Intradural rupture of cervical vertebral disc. AB - STUDY DESIGN: The authors discuss their experience with a patient who had cervical intradural disc herniation and relate the case to the relevant literature. OBJECTIVES: The patient was evaluated with direct radiographies, myelography, electromyography, and computerized tomography, as well as with neurologic examination. The follow-up period was 10 months post-operative. SUMMARY OF BACKGROUND DATA: Intradural disc herniation is a rare pathology nearly always confined to the lumbar region. In 1989, Katooka et al reviewed the existing literature and discovered 70 cases. Cervical intradural disc herniation, on the other hand, is much rarer, and there are only five cases in the literature. METHODS: The patient's neurologic, neuroradiologic, and operative findings were evaluated and compared with the cases reported in the literature. CONCLUSIONS: The five patients in the literature had signs of cord compression, but the present patient is the first with root compression. PMID- 8202807 TI - Lateral distraction injury to the lumbar spine. Report of spontaneous reduction. AB - STUDY DESIGN: A patient with a lateral distraction injury of the lumbar spine that reduced spontaneously and not associated with any thoracic or abdominal injury is reported. SUMMARY OF BACKGROUND DATA: A brief summary of the clinical presentation is given as is the surgical technique employed. Lateral distraction injuries of the thoracolumbar spine associate a distraction injury with lateral bending in the frontal plane, causing unilateral disruption of the ligamentous and osseous restraints. The have been associated with life-threatening thoracic and abdominal injuries. Closed reduction of this spine injury is not believed to be feasible. CONCLUSIONS: This case introduces interesting new features to this spine lesion. It is the first reported case with documented spontaneous reduction. PMID- 8202808 TI - Vertebral hemangioma. Spontaneous spinal canal remodeling after fracture. AB - STUDY DESIGN: The patient in this report had a fracture of a hemangiomatous vertebra with a fragment protruded into the canal and without neurological signs. There was a 12 month follow-up. RESULTS: After conservative treatment, there were no neurologic signs, a good fusion, and natural remodeling of the spinal canal. CONCLUSIONS: The risk of a hemangiomatous vertebra fracture with a fragment retropulsed into the spinal canal and without neurologic signs is low. Also, a remodeling of the spinal canal can occur, as after a burst fracture. PMID- 8202809 TI - Adult diastematomyelia. AB - STUDY DESIGN: This is a rare report of a patient with clinically silent diastematomyelia unrecognized into adulthood. OBJECTIVE: The report demonstrates that diastematomyelia may be clinically silent and may not be evident on routine myelography without computed tomography or magnetic resonance imaging. SUMMARY OF BACKGROUND DATA: A patient presented with lumbar radiculopathy in adulthood. Neurologic examination was normal. Radiographs revealed spina bifida occulta at L5 and the sacrum. Previous myelography demonstrated only a central bulging intervertebral disc at L4-L5. Metrizamide myelography with post-myelography computed tomography demonstrated diastematomyelia with tethered cord. CONCLUSIONS: Myelography alone may be insufficient in demonstrating the pathology described here. Post-myelography computed tomography or magnetic resonance imaging sufficiently demonstrated the abnormality in this patient. PMID- 8202810 TI - Percutaneous discectomy for the treatment of bacterial discitis. AB - METHODS. Percutaneous discectomy was successfully used to diagnose and treat bacterial discitis. CONCLUSIONS. This technique was successful in obtaining a bacteriologic diagnosis, relieving the patient's symptoms and assisting in the eradication of the infection. With percutaneous discectomy, there is lower morbidity and cost than with open treatment. Any comments on the overall effectiveness of this technique will need to be based on additional cases. PMID- 8202811 TI - Spinal manipulation. PMID- 8202812 TI - [Disorders of lactase hydrolysis in patients with ulcerous colitis and irritable colon]. AB - In 28 patients the existence of deficiency in lactase activity was examined indirectly with lactose tolerance test (LTT). Patients were divided in three groups. The first group consisted of 12 patients with confirmed diagnosis of "Irritable-colon syndrome". The second was composed of 6 patients suffering from ulcerative colitis. The third examined group was control group made of healthy persons without any gastrointestinal or metabolic disorders. To exclude the possible of monosaccharide malabsorption, all patients underwent glucose tolerance test (GTT). Milk tolerance questionnaire was performed in all examined patients. All clinical signs were observed for 12 hours after performing LTT. Following the statistical analysis it was found that there was greater frequency of lactose intolerance in two first groups (I and II), comparing with the results obtained in the control group. Low raise of glucose level (less than 1.11 mmol/l) in the majority of patients was connected with characteristic lactose-intolerance clinical signs and symptoms. PMID- 8202813 TI - [Results of combination therapy of inflammatory carcinoma of the breast]. AB - Mastitis carcinomatosa or inflammatory breast cancer (IBC) is a very rare form of breast cancer with aggressive progression, as well as rapid dissemination. Though this disease has been for a long time in focus of interest of clinicians, the problem of its treatment is still unsolved. In the Belgrade Institute of Oncology and Radiology IBC has been already treated with combination of chemotherapy and radiotherapy, and results of such treatment are evaluated and presented in this paper. Taking into account results of the above mentioned treatment as well as that reported in literature, we decided to make its modification. Irradiation was carried out by hyperfractionation, preceded and followed by chemotherapy. Hyper fractionated regime was assessed using LQ model for determination of radiobiological efficiency. The obtained results showed only a percentual, but not statistically significant improvement. The presented treatment was only an attempt after which it could be concluded that the oncologist today, no matter whatsoever he was trying in the treatment of IBC, could not expect extraordinary results, but must be satisfied with the fact that he has given his best help. Nevertheless, we find our attempt valuable since it gives new opportunities for non-conventional radiotherapeutic treatment, as well as new perspectives in the treatment of IBC, but always in combination with systemic therapy. PMID- 8202814 TI - [Epidemiologic characteristics of pancreatic cancer in patients in Belgrade]. AB - Pancreatic cancer mortality was analyzed in Belgrade population over the period from 1975 to 1989. Standardized mortality rate--sbrtshr in 1975-1989--was 5.34/1000 (6.55/1000 in males and 4.32/1000 in females). During the same period the increasing trend of pancreatic cancer mortality was observed in both sexes (y = 4.07 + 0.31x, in males and y = 2.95 + 0.17x, in females). Age specific mortality rates showed low values to the age of 44, but demonstrated sudden increase thereafter, which was more pronounced in males. The proportion of pancreatic cancer among all malignant tumour deaths and among deaths caused by malignant tumours of the digestive tract was slightly increased during the observed period. PMID- 8202815 TI - [Correlation of glycosylated hemoglobin and fructosamine in pregnant women with diabetes mellitus]. AB - Glycolisated hemoglobin (HBA1c), fructosamine, glucose, albumin and total proteins were estimated 40 healthy pregnant women and 90 pregnant women with diabetes mellitus. Fructosamine was estimated by NBT method with "Fructosamine test" commercially available kit on Technicom automatic analyser RA-1000. Glucose was determined on Beckmman glucose analyser. HBA1c was assayed by Bio-Rad test, while albumin and total proteins by Beckmman tests. We found best correlation between fructosamine and HBA1c at pregnant women who were on dietary therapy worst at pregnancy women on insulin therapy. PMID- 8202816 TI - [Modern diagnosis and interventional therapy in ischemic heart disease]. PMID- 8202817 TI - [Clinical importance of measurement of ionized calcium in the blood]. AB - The paper presents new views concerning clinical significance of determining ionized calcium (Ca2+) in the blood for diagnosis, monitoring and therapy of different illnesses. The clinical usefulness, specificity and sensitivity of determining ionized Ca2+ as the only one physiologically active form has been discussed versus determining the total amount of blood calcium the greatest part of which is in bound (inactive) form. PMID- 8202818 TI - [Atrial natriuretic peptides and the kidney]. AB - The aim of this review is to summarize current knowledge about atrial natriuretic peptide (ANP)--its structure, secretion and target organ actions. Due to enormous researches, this review is a summary with special emphasis to the physiologic importance of ANP in humans. In the kidney ANP acts on specific receptors inducing hyperfiltration inhibition of sodium transport and suppression of renin release, effects responsible for natriuresis and diuresis. ANP also lowers blood pressure by inhibiting aldosterone biosynthesis and facilitates transudation of plasma water to interstitium. The current knowledge of ANP physiology is based on the study of blood levels and renal effects of ANP in the presence of different manipulations (variations in dietary sodium intake, posture, water immersion, infusion of synthetic ANP). In healty humans ANP levels rise in response to intravenous loading with saline, by acute dietary sodium overload or by immersion of the body into water. Considering these reactions it is possible that ANP helps to protect the heart from volume overload. PMID- 8202819 TI - [Modern administration (management) of health institutions]. AB - The article deals with the management of health institutions and its different features based on the particularity of health care delivery system. Many countries are in the process of reorganizing management of their health services on the basis of market principles. At the same time health services are facing with the general policy of cost problems in health care, and public expectations for better quality of care. One of the major problems of health care management is to realize these two opposite groups of goal. Many researchers discuss the necessary agreement between managers and doctors in order to find out a good mechanism for an effective organization of health care institutions. They also discuss the former and the present studies of health care management as an important step in the solution of the problem and introduction of changes in the organization of health institutions. Many of them propose systems and operational approaches to management research on the basis of anticipated models in the planning of health care transformation. The main characteristics (contributions and limitations) of such studies are pointed out. PMID- 8202820 TI - [Gonadotropin-releasing hormone analogues in the treatment of metastatic breast carcinoma]. AB - The recent data about the treatment of advanced breast cancer patients with synthetic LH-RH analogues are presented. Although synthetized 20 years ago, the agonistic analogues of LH-RH were introduced in clinical oncology recently. The inhibition of pituitary and gonadal function that occurs after chronic administration of agonists of LH-RH, with the creation of a sex steroid deprivation and elimination of stimulatory effects of oestrogen or testosterone, is the basis for their application in oncology. In advanced breast cancer patients they successfully replace surgical or radiological castration. The main advantage of medical castration is reversibility. However, the discovery of the specific LH-RH receptors effect on mammary tumor membranes as well as on some other tumor cells, suggested the possible direct antitumor effect of LH-RH agonists. This finding enlarge the oncological application of LH-RH agonistic analogues. PMID- 8202821 TI - [Hairy cell leukemia in a patient with type II congenital dyserythropoietic anemia]. AB - The authors report a case of hairy cell leukemia associated with congenital dyserythropoietic anemia type II. This is the first time that the association of these two rare diseases is reported in referential literature. However, simultaneous occurrence of one hereditary and other acquired disease in a 64-year old patient, imposed significant diagnostic problems. PMID- 8202822 TI - [Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes: the POEMS syndrome]. AB - We present a case of an unusual multi-systematic disorder whose cardinal signs were severe progressive sensorimotor polyneuropathy, hepatomegaly, endocrinopathy, plasma cell dyscrasia with osteosclerotic bone lesions and M protein production as well as skin lesions (termed POEMS Syndrome) whose pathophysiology is still unknown, as well as its relationship with myeloma multiplex. The patient, 67 years old, had a history of progressive weakness and numbness of the lower legs, clinically revealed as sensomotor polyneuropathy, hepatomegaly, IgG lambda monoclonal protein in the serum, endocrine abnormalities and skin lesions. The final and definite diagnosis was established by open, surgical biopsy of the second lumbal vertebra. PMID- 8202824 TI - [Congenital mesoblastic nephroma]. AB - Four children with congenital mesoblastic nephroma were treated at the Children's University Hospital in Belgrade, between 1979 and 1990. In relation to the total number of children cured from renal tumours (44), diagnosis of congenital mesoblastic nephroma was confirmed in 9% of all cases with renal tumours. The age of all diagnosed patients was under one year. Three patients developed unilateral and one patient bilateral congenital mesoblastic nephroma. The authors also stress the importance of differential diagnosis between congenital mesoblastic nephroma and other renal tumours, since therapy and prognosis of these tumours are different. In a case of bilateral congenital mesoblastic nephroma that later relapsed with malignant alteration, it is questionable whether bilateral nephrectomy was the most appropriate treatment. PMID- 8202823 TI - [The effect of pre-eclampsia on thyroid gland function]. AB - The prospective study involved 183 pregnant women with disorders of the thyroid gland, who were regularly followed up and delivered at the Department of Gynaecology and Obstetrics, University Clinical Centre, Belgrade, over a period of 10 years (1981-1990). There were 15 euthyroid patients in whom development of pre-eclampsia was diagnosed in the last trimester of pregnancy, and 20 healthy pregnant women with normal pregnancies and termed deliveries. The incidence of pre-eclampsia was analyzed depending on the basic disease, therapy and pregnancy metabolic status, as well as on their influence on the function. A statistically significant higher incidence of pre-eclampsia (p < 0.001) was observed in pregnant women with hyperthyroidism (26.0%) and hypothyroidism (26.8%). On the other hand, in euthyroid patients with pre-eclampsia the authors found that the concentration of total and free thyroxine was somewhat lower, while that of thyroid-stimulating hormone was a little higher comparing to the healthy pregnant women in the last trimester of pregnancy. Similar changes were noticed in patients with hypothyroidism. In pregnant women with hyperthyroidism and pre eclampsia it was established that the concentration of thyroxine and triiodothyronine was somewhat higher, and that concentration of thyroid stimulating hormone was a little lower comparing to all examined women in the equal metabolic condition. In the authors' opinion diseases of the thyroid gland represent a predisposing factor, i.e. a risk factor for the development of pre eclampsia. The aim of further investigation is to observe mutual influences, pathogenetic mechanisms of further development of pre-eclampsia in patients with thyroid disorders, i. e. the influence of pre-eclampsia on thyroid disorders. PMID- 8202825 TI - [Renal carbuncle (abscess)]. AB - The authors report a case of renal carbuncle at 44 year old women. The patient has been presented with high temperature and strong pain in the left costovertebral angle. Diagnosis was based on ultrasonography, intravenous urography and computed tomography and confirmed by percutaneous punction. The patient has been successfully cured by percutaneous drainage and parenteral application of antibiotics. PMID- 8202827 TI - [Injuries in classical ballet dancers]. PMID- 8202826 TI - [Extramedullary blastic transformation in chronic granulocytic leukemia]. AB - A patient with Ph1(Philadelphia chromosome) positive chronic granulocytic leukemia and extramedullary blast transformation (crisis) in lymph nodes of the neck and axillae which appeared after a 4-year treatment with busulfan, is presented. Biopsy of lymph node and histopathological examination showed lymphoblastic infiltration. The patient was treated with radiotherapy and chemotherapy with protocol COP. He survived 7 months and expired due to renal insufficiency. PMID- 8202828 TI - [Development of ophthalmology in Serbia since the founding of the Eye Clinic on 9 July 1921 in Belgrade. 1]. PMID- 8202829 TI - [Magnetic resonance in the diagnosis of pathologic changes in the infundibulum of the hypophyseal gland]. AB - Magnetic resonance imaging (MRI) is a new, non-invasive neuroradiological diagnostic procedure for direct multiplanar visualization of the anatomic structures of pituitary gland infundibulum. MRI is extremely sensitive in demonstrating pathological changes of infundibulum, and is a method of choice for diagnosis of its breakage. Forty-eight patients with pituitary hypofunction have been examined on MRI to demonstrate empty sellae and/or breakage of infundibulum. Pathological changes of infundibulum were found in 11 patients, five of which had breakage (congenital or traumatic). Optimal MRI protocol, with application of paramagnetic contrast agent, for examination of pituitary gland has been established. PMID- 8202830 TI - Recent advances in the treatment of rheumatic diseases: new approaches to immunotherapy. PMID- 8202831 TI - [Human immunoglobulin G carbohydrate chain--its structure, function, and abnormality]. PMID- 8202832 TI - [Immune tolerance, anergy, suppressor T cells]. PMID- 8202833 TI - Pathogenic role of rheumatoid factors. PMID- 8202834 TI - [Comparative pathology of arthritis]. PMID- 8202835 TI - [Immune complex and rheumatoid arthritis]. PMID- 8202836 TI - [Molecular studies in autoimmune diseases]. PMID- 8202837 TI - [Autoimmune diseases and cytokine]. PMID- 8202838 TI - [Superantigens]. PMID- 8202839 TI - [Pathology and treatment of osteoarthrosis deformans of the knee]. PMID- 8202840 TI - [Cytotoxicity and apoptosis]. PMID- 8202841 TI - Social Security programs in the United States, 1993. PMID- 8202842 TI - [The circadian rhythms of the level of ACTH, cortisol and 17 hydroxycorticosteroids in bronchial asthma patients]. AB - The circadian rhythm of hydrocortisone and ACTH in plasma and 17-OCS in the urine were registered in 10 patients with bronchial asthma and 5 healthy subjects. It was found that maximal concentrations of hydrocortisone occurred in the day time whereas those of ACTH at nights in moderate asthma. In its severe forms neither hydrocortisone nor ACTH followed circadian rhythms. It is recommended to treat patients with severe bronchial asthma on the individual basis selecting glucocorticosteroid doses with reference to plasma fluctuations of hydrocortisone. PMID- 8202843 TI - [The fiber bronchoscopic evaluation of the bronchial inflammatory changes and hyperreactivity in bronchial asthma patients]. AB - Bronchofibroscopic bronchial examination detected inflammation-induced changes in the bronchi in the form of mucosal thickening (edema), small masses of the sputum and occasional hyperemia in the majority of the examinees with bronchial asthma. In combination with bronchoalveolar lavage, bronchofibroscopy provides diagnosis of bronchial hyperreactivity basing on determination of segmentary bronchial stenosis in response to salt solution instillation. The degree of this stenosis can evidence the degree of hyperreactivity of the bronchi. Bronchofibroscopic signs of bronchial hyperreactivity appear more distinctly in asthma aggravations, in severe run of the disease, in pronounced inflammation. PMID- 8202844 TI - [A trial of the use of ditek in the clinical picture of allergic diseases]. PMID- 8202845 TI - [The evaluation of the efficacy and safety of dosed aerosols of ditek, berotek and bicromat]. PMID- 8202846 TI - [A comparative study of the efficacy of Tilade and intal in atopic bronchial asthma]. AB - The authors compared the responses of patients with atopic asthma to two cromolyn drugs of different generations, tailed and intal. As shown by clinical, allergological and immunological findings, tailed (sodium nedocromil) compared to intal is more active against atopic bronchial asthma complicated by obstructive bronchitis. It can more efficiently reduce specific and nonspecific bronchial hyperreactivity, is more potent against inflammation. Due to tailed, the need in glucocorticoid inhalation lowered, it became possible to induce a prolonged remission. PMID- 8202847 TI - [Bronchial asthma: a global strategy]. PMID- 8202848 TI - [The efficacy of membrane-stabilizing therapy in bronchial asthma]. AB - Lipid peroxidation was studied in 65 bronchial asthma patients aged 23-56 in aggravation of their disease and after differential therapy. Conventional treatment proved unable to correct either enhanced lipid peroxidation (LPO) or weak antioxidant defense (AOD), whereas the addition to the treatment program of membrano-stabilizers (actovegin, lipostabil) contributed to LPO and AOD normalization, improved bronchial patency and, eventually, produced early remission. PMID- 8202849 TI - [The effect of glucocorticoid hormones on the blood coagulation and fibrinolytic activity of the gastroduodenal mucosa in bronchial asthma patients]. AB - Gastrofibroscopic findings for 164 patients with bacterial asthma (BA) showed high frequency of gastroduodenal ulcer occurrence. Mucosal biopsy extracts from the stomach and duodenum of BA patients demonstrate high hemocoagulative and low anticoagulative activities. Enhanced fibrin-formation in inhibition of fibrinolytic activity in gastroduodenal mucosa vessels causes local circulatory disorders. This fact explains well frequent findings of the ulcer in BA patients. Antibiotic therapy does not affect enzymatic activity of gastroduodenal zone in BA patients and eventually does not aggravate ulcer lesions. Corticosteroid hormones stimulate hemocoagulative activity in the zone and further inhibit anticoagulative activity. This results in further ulceration and appearance of new lesions. PMID- 8202850 TI - [The clinical and structural-metabolic characteristics of atrophic forms of chronic bronchitis]. AB - A clinical-morphological study of bronchobiopsies from 78 patients with endoscopic picture of atrophic endobronchitis was carried out. Two forms of morphogenesis of chronic atrophic process in the bronchial mucosa are distinguished: primary dystrophic and primary inflammatory. Primary dystrophic bronchopathy is a clinical manifestations of the first form which presents structurally and functionally as primary dystrophy and atrophy of the bronchial mucosa in combination with sclerosis of the lamina propria in a sharp decrease of synthetic processes in bronchial epitheliocytes as indicated by the data of autoradiography. The primary inflammatory form of atrophic process has clinical symptoms typical for inflammatory process and is characterized by gradual reorganization in the bronchial wall and by maintaining sufficiently high level of metabolic reactions in bronchial epitheliocytes. PMID- 8202851 TI - [The role of proteolytic enzyme inhibitors in the development and occurrence of chronic obstructive lung diseases]. PMID- 8202852 TI - [The clinico-immunological evaluation of the ribomunyl treatment of chronic bronchitis patients]. AB - The paper reports the results of ribomunil trial in chronic bronchitis (CB) patients who suffered from frequent exacerbations. The drug was found to act primarily on a phagocytic component of the immunity and local immunity of the respiratory mucosa. Because of its vaccine-like effect, ribomunil administration is most beneficial in CB remission. Ribomunil treatment results in reduction of the number and duration of CB exacerbations, of the scope of antibacterial therapy. PMID- 8202853 TI - [The characteristics of the pneumonias found in those who die in the postoperative period]. AB - A clinicomorphological examination of the respiratory organs has been conducted in 25 adults and 30 children who died after abdominal surgery. The authors compared the findings of light and immunofluorescent microscopy with laboratory and clinical evidence. Acute respiratory infections revealed in the examinees appeared of different etiology, many of them proved to be mixed. Viral and Mycoplasma infections were most prevalent and severe. Bacterial pneumonias occurred rarely, were clinically inapparent, often arose preoperatively. Weak aspiration indicated the absence of a direct relation between respiratory infections and disorders of bronchial drainage due to surgery performed. PMID- 8202854 TI - [Acute pneumonias against a background of chronic nonspecific lung diseases]. AB - The origin, course, diagnosis and treatment aspects of acute pneumonia have been studied in 394 patients with chronic bronchitis and 158 bronchial asthmatics. In chronic bronchitis, acute pneumonia was diagnosed resting on clinical physical data in one-third of the patients, the rest cases simulated exacerbations of bronchitis and were detected only at x-ray. Clinical relationships between acute pneumonia and bronchial asthma are variable (prepneumonic asthma aggravation , its early and late severe episodes because of pneumonia). Chronics with nonspecific diseases of the lungs are referred to high-risk-for-pneumonia groups, while acute pneumonias are considered affections negatively influencing background bronchopulmonary disorders. PMID- 8202855 TI - [The role of clinico-pharmacogenetic associations in the prognosis of the outcomes in pneumonias]. AB - In search of reliable genetic markers of protracted and complicated pneumonia, the authors studied blood groups, haptoglobin phenotype, sulfadimisine acetylation. These markers proved essential for predicting pneumonia course and prognosis. PMID- 8202856 TI - [The treatment of bronchopulmonary aspergillosis with allergic manifestations]. AB - The base of current management of bronchopulmonary aspergillosis with allergic manifestations (BPAAM) is glucocorticosteroid treatment. These hormones are introduced in a mean dose 0.5 mg/kg (by prednisolone) to correct bronchial obstruction, reduce eosinophilia and resolve (completely or partially) infiltrates in the lungs. This being achieved, the dose is lowered to warrant maintenance. Minimal doses or discontinuation of glucocorticosteroids may be used in case of adjuvant indomethacin (0.025 three times a day) or plasmapheresis administration. In remission, fungistatic means with glucocorticosteroids or without them (in the absence of bronchial obstruction) are proper. Inhalations in BPAAM are ineffective. Individual schemes of the disease treatment may vary in wide range. PMID- 8202857 TI - [The use of streptokinase preparations in pleural empyema and pyopneumothorax]. AB - Prevailing fibrin-formation in the pleural cavity entails hypoactivity of trypsin like proteinases and a high inhibitory potential in the serum and pleural exudate. Streptokinase preparations appeared an effective means of pharmacological pulmonary decortication in patients with high pleural levels of plasminogen. The authors obtained higher efficacy of conservative therapy for pyothorax when they used a specially designed technique of intrapleural administration of streptokinase-activated fresh frozen plasma of the same group. The outcomes of the disease were also improved noticeably. PMID- 8202858 TI - [The clinico-functional characteristics of pulmonary arterial hypertension in systemic scleroderma]. AB - Electro-, phono-, echo-, and Doppler echocardiography, bulbar biomicroscopy were performed in 54 SS patients aged 18-64. Mean pulmonary arterial pressure (PP) was determined at Doppler echocardiography on Toshiba SSH-40A unit according to techniques developed by M. M. Mirrakhimov et al. in 1989. The diagnosis of pulmonary hypertension (PH) was made in PP above 18 mm Hg. A close relationship was found between SS history and PH registration. With growing SS duration, PH severity increases, microcirculatory disorders progress. Main PH risk factors in SS patients are believed SS duration, activity, Raynaud's syndrome presentation. Doppler echocardiography can effectively diagnose PH in its subclinical stage, is noninvasive. PMID- 8202860 TI - [Primary pulmonary hypertension: questions demanding an answer]. PMID- 8202859 TI - [The comparative effect of calcium antagonists on hemodynamics in patients with a stable form of essential hypertension (a randomized study)]. PMID- 8202861 TI - [The role of disorders in the homeostasis of divalent cations in the pathogenesis and clinical picture of bronchial asthma]. AB - Mg and Ca concentrations in the serum, red cells, lymphocytes and 24-h urine were examined in 13 preasthma (PA) patients, 26 atopic asthma patients and 23 bacterial asthma (BA) patients. The patients' age ranged from 15 to 65 years. The measurements were made on AAC-508 absorption spectrophotometer (Hitachi, Japan) and Microlyte selective ionometer (Kone, Finland). Lack of Mg and excess of Ca in blood cells and low Mg values in circadian urine were recorded in all the patients irrespective of the disease variant, phase, course, broncho-obstruction. Changes in cell electrolyte composition in asthma and PA patients seem to disturb cAMP metabolism and to enhance lipid peroxidation, thus being responsible for bronchial hyperreactivity. Superactivation of free-radical lipid peroxidation in cellular membranes is suggested to underlie, among other factors, defective intracellular homeostasis of bivalent cations in the above patients. PMID- 8202862 TI - [Pleural exudates (terminology, classifications and differential diagnosis)]. PMID- 8202863 TI - [The treatment of the sleep apnea syndrome by prolonged positive air pressure]. PMID- 8202864 TI - [Multifocal atrial tachycardia]. PMID- 8202865 TI - The use of Paxirasol in clinical practice. AB - Summarizing the observations of foreign and Hungarian investigators it may be concluded that: 1. Bromhexine is an expectorant of outstanding effect which has virtually no side-effects when used in therapeutic doses; by loosening the thick, sticky mucus in increases the effectivity of mucociliary clearance and hinders the infection of thick excretion sticking to the mucosa. 2. It promotes the diffusion of antibiotics into the lung tissue. 3. Considering the increasingly important aspects of "cost-benefit", the use of drug is also advantageous. 4. In addition to the traditional drug forms (tablet, injection, solution) new forms of the drug (inhalation aerosol, nasal spray) increase its indication field to a high degree. These allow to apply local expectorant-mucolytic therapies and to successfully treat the so-called sicca diseases (rhinitis sicca, pharyngitis sicca, etc.), which frequently occur in laryngological practice and was difficult to influence until present. PMID- 8202866 TI - Clinical results with Taleum in the treatment of extrinsic bronchial asthma. AB - Taleum inhalation aerosol, produced by EGIS Pharmaceuticals Works, was examined in an 8-week open cross-over self-controlled study in 50 patients suffering from extrinsic bronchial asthma. Intal powder capsule inhaled with the aid of a spinhaler was used as a reference drug. Changes in subjective complaints and symptoms were continuously recorded on a score scale in the patients' diary. The alterations in respiratory parameters were measured. Laboratory parameters were monitored. On the basis of the results Taleum spray was found to be effective in the prevention of bronchial asthma. It proved to be a well tolerated drug form of simple use. PMID- 8202867 TI - Possible use of Betadine in HIV-positive patients. AB - The results of Betadine treatment obtained in the course of a one-year period proved the usefulness of the bacteriostatic and bactericidal product as a disinfectant of the skin and mucosa in immuno-deficiency diseases, in our cases in AIDS (but supposedly in other similar diseases as well). In these diseases this new therapeutic means does supply a need. The solution was successfully used in patients in whom superficial decontamination is of high importance and whose cutaneous and mucosal infections had raised therapeutic problems for years. Side effects were not observed. The product could be easily applied. If the germ count of the atrophying pathogen is not very high and the lesion is due supposedly to mixed infection, the product will be effective even in monotherapy. Similarly, in mild mycotic infections systemic therapy could be avoided. In cases of purulent alterations the solution is successfully applied as an adjuvant to antibacterial treatment and its continuous use prevents early recurrence. The long-term use of the product did not cause side-effects, irritation of the skin or the mucosa. PMID- 8202868 TI - Clinico-bacteriological examination of Betadine skin disinfectant fluid and liquid soap in hospitalized patients and hospital employees. AB - The effectivity of Betadine skin and mucosa disinfectant solution and Betadine hand disinfectant soap (MUNDIPHARMA A. G. and EGIS Pharmaceuticals has been examined in hospitalized patients and hospital employees. The history of the production of polyvynilpyrrolidone-iodine (PVP-Iodine) the mechanism of actions and the biological effects of these products have been discussed. Bacteriological samples were collected from the skin of four regions most frequently used for injection (fossa cubitalis, right and left hands and gluteal region, right and left sides) of 10 hospitalized patients before and after washing these regions with Betadine. The average of 68 microorganisms Colony Forming Unit (CFU) recorded before disinfection decreased below 1 CFU on average in the samples taken after disinfection. From both hands of 6 hospital employees 190 CFUs could be demonstrated following washing hands with the commonly used soap. After washing hands with Betadine soap a total of 1 CFU could be demonstrated. The hands of 44 hospital employees were infected with E. coli of non-pathogenous reference strain whereafter samples were collected. After the disinfection of the hands with Betadine liquid soap samples were taken again. In the samples taken before disinfection an average of 745 CFUs, in samples taken after disinfection an average total of 11 CFUs were found. The results prove the outstanding disinfectant action of the two examined Betadine products. PMID- 8202869 TI - In memoriam Gyorgy Gortvay (1892-1966), his life. Dedicated to health politics and medical history. PMID- 8202870 TI - Placebo-controlled clinical trial of Dormicum 15-mg tablet. AB - In 60 insomnia patients placebo-controlled clinical examinations were performed with Dormicum hypnotic containing 15 mg midazolam active substance and made available by EGIS Pharmaceuticals. The patients involved in the study lived a normal life and belonged to both sexes. In the introduction the author summarizes the different forms of pathological sleep and discusses the pharmacology of some hypnotics on the basis of which a detailed, multifactorial, up-to-date clinical examination of a hypnotic should be planned. He uses up-to-date methods and means for the examination of the drug which meet the requirements of an adequate clinical testing of a hypnotic. The sleep disturbances of the patients have been classified and characterized by the author from the somnological aspects and with somnological methods. Patients with sleep onset, sleep maintenance, early morning, as well as mixed insomnias were differentiated. The effectivity of the drug was evaluated on the basis of data of sleep questionnaires referring to the target symptoms and the results of 24-hour polygraphic monitorings performed in 18 patients. In addition, the eventual hangover effect of the drug was assessed in these patients on the basis of the changes in reaction time, pulse rate, and skin resistance measured by polygraphy, besides placebo control on the day following the intake of the drug. The neurological and other organic side-effects were also examined and registered by means of the self-evaluating questionnaires, target specific interviewing of the patients, as well as by laboratory examinations. The drug proved to be most valuable as a hypnotic in patients with sleep onset and mixed insomnias. The hypnotic action was not so definite in sleep maintenance insomnias, the poorest responses were obtained in early morning insomnia cases. According to the results of polygraphic sleep examinations the two first sleep cycles become normal following the intake of the hypnotic. Parameters characteristic of REM sleep do not show changes. In the examined patients the number of side- and hangover effects attributable to the drug was very low. The author calls the attention to the importance of the observance of the dosage and administration of the drug which may prevent the development of a great number of side-effects. By giving a detailed description of a case history of an insomniac patient the author illustrates how the application field of midazolam may be further extended--within the frames of a sleep therapeutic process. PMID- 8202871 TI - New insights into the pathogenesis of interstitial pulmonary fibrosis. PMID- 8202872 TI - Recent developments in research into sudden infant death. PMID- 8202873 TI - Occupational asthma among hospital health care personnel: a cause for concern? PMID- 8202874 TI - Type I collagen formation in rat type II alveolar cells immortalised by viral gene products. AB - BACKGROUND: Alveolar type II (T2) cells synthesise matrix proteins such as type IV collagen and fibronectin. In contrast, a fetal rat T2 cell line has been shown to synthesise type I and III collagen as well as type IV collagen. To study regulation of collagen production in T2 cells, neonatal T2 cells immortalised by adenoviral 12SE1A gene transfer were used. It was previously reported that this immortalised cell line (E1A-T2) retains epithelial features such as tight junctions and cytokeratins but also expresses mesenchymal features such as vimentin. METHODS: Collagen production was examined in E1A-T2 and primary neonatal T2 cells using polyacrylamide gel electrophoresis. Electron microscopy was used to examine collagen deposition in E1A-T2 cell culture. To define the mechanism by which alpha 1(I) type I collagen gene expression was activated in E1A-T2 cells, a deletional analysis of alpha 1(I) promoter constructs linked to the bacterial chloramphenicol acetyltransferase gene was performed. RESULTS: E1A T2 cells produced large amounts of type I collagen with a predominance of alpha 1(I) homotrimers; alpha 2(I) peptides were detected only in the cell layer. In contrast, primary neonatal rat T2 cell cultures produced a trace amount of type I collagen. Production of alpha 1(I) peptide chains (per microgram DNA) in E1A-T2 cell cultures was 30 times higher than that observed in primary neonatal T2 cell cultures. Electron microscopy showed deposition of type I collagen fibrils in the extracellular matrix of E1A-T2 cell cultures. Transfection studies suggested at least two cis-acting elements which mediate increased alpha 1(I) gene expression in E1A-T2 cells. CONCLUSIONS: These studies indicate that the E1A-T2 cell line may be useful for studying type I collagen gene regulation in alveolar T2 cells. These findings also raise the possibility that viral activation of type I collagen genes in alveolar epithelium may be involved in certain forms of pulmonary fibrosis. PMID- 8202875 TI - Effect of fluticasone propionate on neutrophil chemotaxis, superoxide generation, and extracellular proteolytic activity in vitro. AB - BACKGROUND: Corticosteroids are widely used in the treatment of many inflammatory conditions but the exact mode of action on neutrophil function is uncertain. Fluticasone propionate is a new topically active synthetic steroid which can be measured in body fluids and which undergoes first pass metabolism. METHODS: The effects of fluticasone propionate on the function of neutrophils isolated from normal, healthy control subjects and on the chemotactic activity of sputum sol phase were assessed. RESULTS: Preincubation of neutrophils with fluticasone propionate reduced the chemotactic response to 10(-8) mol/l F-Met-Leu-Phe (FMLP) and to a 1:5 dilution of sputum sol phase in a dose dependent manner. Furthermore, when fluticasone propionate was added to sputum from eight patients with stable chronic obstructive bronchitis the chemotactic activity of a 1:5 dilution of the sol phase fell from a mean (SE) value of 22.2 (1.21) cells/field to 19.6 (0.89), 17.1 (0.74), and 11.9 (0.6) cells field at 1 mumol/l, 10 mumol/l, and 100 mumol/l, respectively. In further experiments fluticasone propionate preincubated with neutrophils inhibited fibronectin degradation by resting cells and by cells stimulated by FMLP (15.2% inhibition of resting cells, 5.1% inhibition of stimulated cells with 1 mumol/l fluticasone propionate, 24% and 18.7% inhibition respectively at 100 mumol/l fluticasone propionate. Fluticasone propionate had no effect on generation of superoxide anion by resting or stimulated cells. CONCLUSIONS: These results indicate that fluticasone propionate has a direct suppressive effect on several aspects of neutrophil function and may suggest a role for this agent in the modulation of neutrophil mediated damage to connective tissue. PMID- 8202876 TI - Clinical relevance of testing for antineutrophil cytoplasm antibodies (ANCA) with a standard indirect immunofluorescence ANCA test in patients with upper or lower respiratory tract symptoms. AB - BACKGROUND: Reports from specialist nephrological centres have suggested that the antineutrophil cytoplasm antibody (ANCA) test is highly specific and sensitive for patients with Wegener's granulomatosis. To determine the usefulness of the ANCA test in everyday respiratory practice the results of the test were audited in all patients in the south west of England with respiratory symptoms who underwent the test. METHODS: The results of all 335 patients who had presented with upper or lower respiratory tracts symptoms, or both, and were tested for ANCA by the indirect ANCA test in 1990, as recommended in the broadsheet of the British Association of Clinical Pathologists, were audited. Case notes and necropsy reports were available for review in 231 cases (69%), and in the remainder information was obtained by a standard questionnaire. RESULTS: There were 106 positive results, 45 (44%) from patients with Wegener's granulomatosis. The sensitivity and specificity of a positive ANCA test result in this study were 65% and 77% respectively. For a diagnosis of Wegener's granulomatosis the sensitivity and positive predictive accuracy of a positive cytoplasmic ANCA (c ANCA) test were greater than of a positive perinuclear ANCA (p-ANCA) test. There were 61 positive tests in 266 patients who did not have Wegener's granulomatosis (23%); of these 27 were from patients with infection, 10 with fibrotic lung disease, nine with underlying connective tissue disease, seven with malignancy, and five following pulmonary emboli. Most of these positive ANCA results were p ANCA (69%) rather than c-ANCA (31%). Serial ANCA requests were made in 15 cases of patients without Wegener's granulomatosis who had an initial positive ANCA test result. In all cases the ANCA tests subsequently became negative. CONCLUSIONS: In this study the sensitivity and specificity of a positive ANCA test result were less than that reported from specialised centres. However, the test was found to be useful in clinical practice, especially c-ANCA, in conjunction with clinical symptoms of respiratory pathology and evidence of renal disease. PMID- 8202877 TI - Circulating antibodies to lung protein(s) in patients with cryptogenic fibrosing alveolitis. AB - BACKGROUND: It has been hypothesised that cryptogenic fibrosing alveolitis has an immunological pathogenesis mediated by T lymphocytes. It is, however, recognised that patients may show dysregulation of the humoral immune system and that the presence of large numbers of B lymphocytes in open lung biopsies may be associated with a poor prognosis. Evidence of a role for the humoral immune system in the pathogenesis of cryptogenic fibrosing alveolitis has been suggested, but attempts to demonstrate circulating immunoglobulin to antigen within the lung have been inconclusive. METHODS: Plasma samples from 22 patients with cryptogenic fibrosing alveolitis, 22 patients with sarcoidosis, and 17 healthy controls were screened by SDS-PAGE and Western blotting for the presence of autoantibodies to lung proteins derived from cryptogenic fibrosing alveolitis, sarcoid and control lung tissue, as well as four normal non-pulmonary tissues. Possible site(s) of target protein(s) within the lung tissue were identified by immunohistochemical examination using IgG purified from the plasma of six patients and two controls. RESULTS: Eighteen of the plasma samples from patients with cryptogenic fibrosing alveolitis had reactive IgG to lung protein(s) in the 70-90 kDa molecular weight range compared with five of 18 plasma samples from patients with sarcoidosis and one of 17 controls. Plasma from patients with cryptogenic fibrosing alveolitis recognised antigen(s) of the same molecular weight in control and sarcoid lung tissue, but not non-pulmonary tissues, with a similar frequency. Immunohistochemical staining of cryptogenic fibrosing alveolitis biopsy material using IgG purified from plasma samples from patients with cryptogenic fibrosing alveolitis, but not control samples, revealed fine linear positivity in the lung parenchyma in a pattern suggestive of reaction with alveolar lining cells. The pattern was cytoplasmic/membranous and not nuclear. CONCLUSIONS: Patients with cryptogenic fibrosing alveolitis have a high frequency of plasma IgG autoantibodies to protein(s) within lung tissue associated with alveolar lining cells. This is believed to be the site where immunological injury occurs in cryptogenic fibrosing alveolitis, but the significance of these antibodies to the aetiology and pathogenesis is as yet unclear. PMID- 8202878 TI - Transforming growth factor beta 1 gene expression in human airways. AB - BACKGROUND: Asthmatic airways have a characteristic deposition of connective tissue under the epithelial basement membrane, but the mediators involved in this alteration are unknown. Several authors have postulated that transforming growth factor beta 1 (TGF-beta 1) could be overexpressed in asthmatic airways. METHODS: Lung samples from 16 asthmatic patients, six patients with chronic obstructive pulmonary disease (COPD), and six non-obstructed smokers were analysed. RNA was extracted from these tissues to measure expression of TGF-beta 1 by Northern blot analysis using a cDNA probe for TGF-beta 1. The level of expression was quantitated by densitometry using glyceraldehyde 3-phosphate dehydrogenase mRNA as a control. TGF-beta 1 was localised to specific cell types in these lungs by immunohistochemical analysis using polyclonal antibodies specific for intracellular and extracellular TGF-beta 1. RESULTS: The 2.5 kb TGF-beta 1 mRNA was seen in all 18 samples analysed by Northern blotting and densitometric analysis showed no difference between the asthmatic group (mean (SD) 108% (43%)), the group with COPD (122% (33%)), and the non-obstructed group (100% (49%)). The TGF-beta 1 precursor was immunolocalised throughout the airway wall including the epithelium and in alveolar macrophages. The mature TGF-beta 1 was localised primarily within the connective tissue of the airway wall. These patterns of expression of both forms of TGF-beta 1 were similar in lungs from asthmatic patients, those with COPD, and controls. CONCLUSIONS: While TGF-beta 1 mRNA and protein are abundantly expressed in human lungs, there is no clear difference in expression between the airways of asthmatic subjects and those of smokers with and without COPD. PMID- 8202879 TI - Haemodynamic effects of atrial natriuretic peptide in hypoxic chronic obstructive pulmonary disease. AB - BACKGROUND: Pulmonary artery pressure is elevated in patients with advanced chronic obstructive pulmonary disease (COPD). Release of atrial natriuretic peptide (ANP) is increased in pulmonary hypertension and this hormone may both selectively vasodilate pulmonary vessels and inhibit pulmonary vascular remodelling. The hypothesis that ANP has a physiological role in protection of the pulmonary circulation from pressure overload, and that it may be beneficial in patients with COPD, has been examined. METHODS: Ten patients with hypoxic COPD were infused for 30 minute periods with saline followed by ANP at 0.4, 2, and 10 pmol/kg/min respectively via a pulmonary artery catheter whilst monitoring haemodynamics and oxygenation. RESULTS: Levels of immunoreactive ANP (irANP) increased from a mean (SD) of 23 (15) pmol/l to a maximum of 94 (41) pmol/l. Neither systemic blood pressure, cardiac output nor total systemic vascular resistance showed any correlation with irANP levels. There were negative correlations between levels of ANP and mean pulmonary artery pressure which fell from 28.7 to 25.9 mm Hg, pulmonary artery wedge pressure which fell from 6.5 to 4.6 mmHg, and total pulmonary vascular resistance which fell from 489 to 428 dynes s cm-5. There was a small fall in PaCO2 from 6.2 to 5.9 kPa, whilst venous admixture and oxygen delivery both increased non-significantly. CONCLUSIONS: At these pathophysiological concentrations there was evidence that ANP selectively reduced right ventricular afterload. These data support the hypotheses that increased plasma levels of ANP may be beneficial in hypoxic COPD, and that endogenous ANP may ameliorate pulmonary hypertension in humans. PMID- 8202880 TI - Respiratory effort perception at rest and during carbon dioxide rebreathing in patients with dystrophia myotonica. AB - BACKGROUND: Breathlessness appears to be closely related to the perception of the outgoing motor command to breathe and should be increased in the presence of muscle weakness. However, breathlessness is not a common symptom in patients with chronic muscle disease who have weak respiratory muscles. The factors that determine the perception of respiratory effort in such patients have not been examined. METHODS: The inspiratory effort sensation during resting breathing and progressive hypercapnia was investigated in 12 patients with dystrophia myotonica with weak respiratory muscles (nine men and three women of mean (SD) age 41.1 (10.5) years; maximum inspiratory pressure 43.1 (17.2) cm H2O) and an age and sex matched control group of normal subjects of mean age 39.6 (10.6) years and a maximum inspiratory pressure of 123 (15.2) cm H2O. RESULTS: During resting breathing with a mouthpiece no differences were seen in inspiratory effort sensation, mouth occlusion pressure, or tidal volume, but inspiratory time and cycle duration were significantly shorter in the patients with dystrophia. Minute ventilation (VE) was significantly higher in the patients (15.8 (4.0) l/min v 12.5 (2.6) l/min), while resting breathing was no more variable in the patients than in controls. The ventilatory response to carbon dioxide (VE/PCO2) was not significantly lower in the patients (14.9 (6.9) l/min/kPa) than in the controls (17.4 (4.3) l/min/kPa). Effort sensation responses to carbon dioxide driven breathing were similar in the control subjects and the patients. With regression analysis of pooled data neither maximum inspiratory pressure nor disease state contributed to perceived inspiratory effort during hypercapnia. CONCLUSIONS: Moderately severe global respiratory muscle weakness does not appear to influence the ventilatory response to rising carbon dioxide tension or the perception of inspiratory effort in patients with dystrophia myotonica. PMID- 8202881 TI - Cross refractoriness between sodium metabisulphite and exercise induced asthma. AB - BACKGROUND: Exercise and inhaled sodium metabisulphite are thought to cause bronchoconstriction in asthma through different mechanisms. The response to both stimuli becomes refractory with repeat challenge. The mechanism of refractoriness is unclear, although depletion of mast cell derived mediators or neurotransmitters has been suggested. Recent studies suggest a common mechanism involving release of inhibitory prostaglandins. If this is true, exercise and sodium metabisulphite induced bronchoconstriction should show cross refractoriness. METHODS: Thirteen subjects with mild asthma and previously established exercise and sodium metabisulphite induced bronchoconstriction performed two sodium metabisulphite challenges (giving a single dose previously shown to cause a 20% fall in FEV1) on one study day, and two exercise tests on another. The second challenge proceeded after recovery (FEV1 > 95% baseline) from the first. Subjects then attended on two further occasions when an exercise test was performed after sodium metabisulphite and a sodium metabisulphite challenge after exercise. RESULTS: When expressed as the percentage reduction in the area under the change in percentage FEV1 curve over 20 minutes (AUC) the response to exercise was reduced by a mean 62.3% (95% CI 46.5% to 78.1%) following a first exercise challenge, and by 50.7% (95% CI 27.8% to 73.6%) following a sodium metabisulphite challenge. The response to a sodium metabisulphite challenge was reduced by a mean of 80.2% (95% CI 68.9% to 91.5%) when it followed a sodium metabisulphite challenge, and by 37.3% (95% CI 15.1% to 59.5%) following an exercise challenge. CONCLUSION: This study shows some cross refractoriness between exercise and sodium metabisulphite induced bronchoconstriction, in keeping with a partially shared mechanism of refractoriness. PMID- 8202882 TI - Comparison of sulphur dioxide and metabisulphite airway reactivity in subjects with asthma. AB - BACKGROUND: In asthmatic subjects bronchoconstriction is induced by inhalation of the common food preservatives sulphur dioxide (SO2) and metabisulphite (MBS). SO2 and MBS challenges share many similarities, but it is not known whether they are equivalent. In this study of subjects with mild clinical asthma equivalence was assessed by comparing SO2 and MBS reactivity by estimating the total dose of SO2 inhaled during SO2 and MBS challenges, and by calculating SO2 uptake during both challenges. In addition, as the MBS solutions inhaled were acidic and hyperosmolar, the effect of these factors on MBS responsiveness was investigated. METHODS: Fifteen subjects were challenged on separate days with doubling (0.5 to 8.0 ppm) concentrations of SO2 gas inhaled during three minute periods of isocapnic hyperventilation and MBS administered in doses ranging from 0.1 to 12.8 mumol using the Wright protocol. On two other days SO2 and MBS challenges were preceded by a challenge with phosphate buffered saline (PBS) solutions of pH and osmolarity similar to MBS solutions. Response was measured as the dose or concentration causing a 20% fall in FEV1 (PD20 or PC20). RESULTS: All subjects reacted to MBS and 14 responded to SO2. Geometric mean histamine PD20 was 1.61 mumol (95% confidence interval 0.72 to 3.60). MBS and SO2 airway responsiveness were not significantly related. Estimates of the mean concentration of SO2 inhaled during SO2 and MBS challenges differed, as did estimates of the mean SO2 uptake during both challenges. MBS and SO2 reactivity were not affected by prior challenge with PBS solutions. CONCLUSIONS: SO2 and MBS challenges are not comparable. MBS reactivity was not affected by the hyperosmolar, acidic nature of its solutions. PMID- 8202883 TI - Role of inflammation in nocturnal asthma. AB - BACKGROUND: Nocturnal airway narrowing is a common problem for patients with asthma but the role of inflammation in its pathogenesis is unclear. Overnight changes in airway inflammatory cell populations were studied in patients with nocturnal asthma and in control normal subjects. METHODS: Bronchoscopies were performed at 0400 hours and 1600 hours in eight healthy subjects and in 10 patients with nocturnal asthma (> 15% overnight fall in peak flow plus at least one awakening/week with asthma). The two bronchoscopies were separated by at least five days, and both the order of bronchoscopies and site of bronchoalveolar lavage (middle lobe or lingula with contralateral lower lobe bronchial biopsy) were randomised. RESULTS: In the normal subjects there was no difference in cell numbers and differential cell counts in bronchoalveolar lavage fluid between 0400 and 1600 hours, but in the nocturnal asthmatic subjects both eosinophil counts (median 0.11 x 10(5) cells/ml at 0400 hours, 0.05 x 10(5) cells/ml at 1600 hours) and lymphocyte numbers (0.06 x 10(5) cells/ml at 0400 hours, 0.03 x 10(5) cells/ml at 1600 hours) increased at 0400 hours, along with an increase in eosinophil cationic protein levels in bronchoalveolar lavage fluid (3.0 micrograms/ml at 0400 hours, 2.0 micrograms/l at 1600 hours). There were no changes in cell populations in the bronchial biopsies or in alveolar macrophage production of hydrogen peroxide, GM-CSF, or TNF alpha in either normal or asthmatic subjects at 0400 and 1600 hours. There was no correlation between changes in overnight airway function and changes in cell populations in the bronchoalveolar lavage fluid. CONCLUSIONS: This study confirms that there are increases in inflammatory cell populations in the airway fluid at night in asthmatic but not in normal subjects. The results have also shown a nocturnal increase in eosinophil cationic protein levels in bronchoalveolar lavage fluid, but these findings do not prove that these inflammatory changes cause nocturnal airway narrowing. PMID- 8202884 TI - Compliance with CPAP therapy in patients with the sleep apnoea/hypopnoea syndrome. AB - BACKGROUND: Continuous positive airway pressure (CPAP) therapy is the treatment of choice for the sleep apnoea/hypopnoea syndrome. Compliance with this relatively obtrusive therapy has not been well studied. METHODS: Usage of CPAP was investigated in 54 patients with sleep apnoea/hypopnoea syndrome (median 36 (range 7-129) apnoeas + hypopnoeas/hour slept) over the first 1-3 months after starting CPAP therapy. In all cases CPAP usage was monitored by hidden time clocks that indicated for how long the machines were switched on--that is, the CPAP run time. In 32 patients the time at which the CPAP mask pressure was at the therapeutic level of CPAP pressure set for that patient--that is, the mask time- was also monitored. In all patients objective daytime sleepiness was assessed by multiple sleep latency before and after CPAP therapy. RESULTS: The mean (SE) nightly CPAP run time was 4.7 (0.4) hours. There was no correlation between run time and severity of the sleep apnoea/hypopnoea syndrome as assessed by apnoea + hypopnoea frequency or multiple sleep latency, and no correlation between CPAP usage and improvement in multiple sleep latency. Thirty two patients in whom mask time was recorded had therapeutic CPAP pressures for 89% (3%) of their CPAP run times. Patients who experienced side effects from CPAP used their CPAP machines significantly less than those who did not. CONCLUSIONS: Patients with sleep apnoea/hypopnoea syndrome used CPAP for less than five hours/night on average with no correlation between severity of sleep apnoea/hypopnoea syndrome and CPAP usage. Patients who complained of side effects used their CPAP therapy less. It is recommended that, as a minimum, CPAP run time should be regularly recorded in all patients receiving CPAP therapy. PMID- 8202885 TI - Effect of adding aminophylline infusion to nebulised salbutamol in severe acute asthma. AB - BACKGROUND: The benefit of adding theophylline to beta 2 agonists in acute asthmatic attacks has been debated frequently. METHODS: In an open randomised study 25 patients with severe acute asthma who presented to the emergency department were treated with either a combined nebulised salbutamol (5 mg/dose) and aminophylline infusion (0.6-0.9 mg/kg/hour), or nebulised salbutamol alone. RESULTS: The responses to treatment as measured by peak expiratory flow (PEF) and the time taken to achieve maximum PEF were similar in both groups. Side effects were observed more commonly in patients receiving the combined treatment. CONCLUSIONS: Nebulised salbutamol is equally efficacious in acute asthma when given alone or in combination with aminophylline. PMID- 8202887 TI - Pulmonary rehabilitation in chronic respiratory insufficiency. 9. How to keep the customer satisfied. PMID- 8202886 TI - Pulmonary rehabilitation in chronic respiratory insufficiency. 8. Setting up a pulmonary rehabilitation programme. PMID- 8202888 TI - Spontaneous migration of totally implanted venous catheter systems from subclavian into jugular veins. AB - Two cases of migration of totally implanted catheter systems are described. The complication is potentially life threatening. PMID- 8202889 TI - Anterior mediastinal mass in a young man. AB - The case is presented of a patient in whom the diagnosis of Klinefelter's syndrome was made only after a mediastinal teratoma was discovered. Chest physicians should be aware of this association since they are often the first to evaluate patients with mediastinal masses. PMID- 8202890 TI - Foregut duplication cyst presenting as neonatal respiratory distress and haemoptysis. AB - The case history is described of an infant, with a thoracic foregut duplication cyst containing a perforated peptic ulcer, who presented with haemoptysis and respiratory distress. This presentation is discussed within the context of thoracic foregut duplications. PMID- 8202891 TI - Improvement in sodium cromoglycate delivery from a spacer device. PMID- 8202892 TI - Photodynamic therapy for treatment of bronchial carcinomas. PMID- 8202893 TI - Variability in ciliary beat frequency in bronchiectasis. PMID- 8202894 TI - Consumer, carer, provider, purchaser--developing care for adults with cystic fibrosis: a specialist service. PMID- 8202895 TI - Bronchiolitis and asthma: are they related? PMID- 8202896 TI - Ventilation in severe acute asthma: is there safety in numbers? PMID- 8202897 TI - Hospital care for adults with cystic fibrosis: an overview and comparison between special cystic fibrosis clinics and general clinics using a patient questionnaire. AB - BACKGROUND: Provision of medical care for adult patients with cystic fibrosis is an increasing problem as the number of patients surviving into adulthood increases. Recent reports have suggested that care is best provided in specialist centres because of longer survival. Recent changes in the National Health Service funding and delivery of service may adversely affect the provision of such a specialist service. The aim of this study was to assess the current pattern of medical service received by adults with cystic fibrosis and to compare the type of care between special cystic fibrosis and general clinics. METHODS: Confidential postal questionnaires were sent to all 1052 members of the Association of Cystic Fibrosis Adults (ACFA) comprising 59% of the UK population of cystic fibrosis patients over 15 years and 80% over 25 years of age. The response rate was 82%. RESULTS: Two thirds of patients were attending special cystic fibrosis clinics for either adults or adults and children. There were significant differences in the proportion of patients using special cystic fibrosis clinics between regions but not between social class groups. Significant differences between cystic fibrosis and general clinics were noted. Patients attending cystic fibrosis clinics were more likely to have had simple clinical investigations (blood tests, sputum culture, oxygen saturation, chest radiography, weight and lung function measurement) in the previous year. They were also more likely to have received intravenous antibiotics at home, and to have access to paramedical personnel. Patients attending cystic fibrosis clinics were taking higher doses of pancreatic enzyme supplements with respect to quantity and potency of preparation. Such patients also had less severe symptoms irrespective of social class, and were more likely to be satisfied with professional aspects of their care. Regardless of type of clinic, potential deficiencies were identified in overall medical care with omission of clinical investigations in severely affected patients and evidence of undertreated respiratory and digestive symptoms in patients with moderate and severe disease. CONCLUSIONS: This survey provides evidence that adults with cystic fibrosis attending special cystic fibrosis clinics receive more intensive care, have better symptom control, and are more satisfied with the service provided than those attending general clinics. PMID- 8202898 TI - Inhibition of sodium metabisulphite induced bronchoconstriction by frusemide in asthma: role of cyclooxygenase products. AB - BACKGROUND: Inhaled frusemide inhibits airway responses to sodium metabisulphite and other indirect bronchial challenges in asthma by undetermined mechanisms which may relate to its ability to stimulate prostaglandin release. Inhalation of sodium metabisulphite provokes indirect bronchoconstriction, possibly by activating sensory nerves. To investigate the role of cyclooxygenase products in the airway actions of frusemide and sodium metabisulphite, the effects of a potent cyclooxygenase inhibitor, flurbiprofen, alone and in combination with frusemide were investigated against airway responsiveness to sodium metabisulphite. METHODS: In a double blind double placebo controlled study, 12 mild asthmatic subjects attended on four occasions to undergo three inhalation challenges with sodium metabisulphite. A baseline challenge was performed one hour before oral intake of flurbiprofen 200 mg or matched placebo, and two hours before inhalation of frusemide 40 mg or matched placebo. A second challenge was performed immediately after inhalation of frusemide (two hours after flurbiprofen) with a further challenge three hours later. The log concentration provoking a 20% fall in FEV1 (log PC20) was used to assess airway responsiveness to sodium metabisulphite. RESULTS: Frusemide caused an immediate 1.9 doubling dose protection and a lesser 0.7 doubling dose protection at three hours. This protection was enhanced by flurbiprofen at both time points to 2.7 (early) and 1.9 (late) doubling doses. In addition, flurbiprofen alone significantly reduced airway responsiveness to sodium metabisulphite by 1.1 doubling doses at both two and five hours. CONCLUSIONS: The generation of bronchoprotective prostaglandins is unlikely to underlie the inhibitory action of frusemide against airway responsiveness to sodium metabisulphite. Endogenous contractile prostaglandins within the airways may be involved in the bronchoconstrictor response to sodium metabisulphite. PMID- 8202899 TI - Collagen breakdown products and lung collagen metabolism: an in vitro study on fibroblast cultures. AB - BACKGROUND: In fibrotic diseases such as pulmonary fibrosis there is evidence suggesting enhanced synthesis and degradation of lung connective tissue components, including collagen. It has therefore been hypothesised that products of collagen degradation may have a role in the promotion of collagen deposition. In support of this hypothesis, it has recently been shown that intravenous injection of lung collagen degradation products in experimental animals stimulated collagen synthesis leading to increased collagen deposition and diffuse interstitial lung disease. METHODS: Rabbit and human fibroblast cultures from lung and skin were used as an in vitro model to study the responses of these cells to rabbit collagen degradation products. The effects of an acute exposure to collagen degradation products on synthesis of collagen and noncollagenous protein have been studied in confluent cultures by [3H]-proline incorporation. The effects of collagen degradation products on fibroblast proliferation and production of genetic types of collagen have also been investigated. RESULTS: The acute exposure of rabbit lung fibroblast cultures to collagen degradation products significantly increased collagen synthesis without affecting non collagenous protein synthesis. This effect was dose related, specific for lung fibroblasts, and species specific. Collagen degradation products altered the rate of synthesis of genetic types of collagen with a consequent decrease of type III/I+III collagen ratio (0.26 (0.04) treated with collagen degradation products; 0.45 (0.02) controls). These effects occurred without the intervention of serum factors. In addition, collagen degradation products neither affected fibroblast proliferation nor selected specific clones emphasising one type of collagen. CONCLUSIONS: These results suggest that collagen degradation products can influence lung collagen metabolism by stimulating collagen synthesis. The regulation of collagen mass by collagen degradation products may be of importance in lung collagen homeostasis in vivo. PMID- 8202900 TI - Collagen content of alveolar wall tissue in emphysematous and non-emphysematous lungs. AB - BACKGROUND: Emphysema is currently defined as "a condition of the lung characterised by abnormal, permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls, and without obvious fibrosis." The functional and morphological changes that occur in emphysema have largely been attributed to changes in alveolar elastin rather than in collagen. A study was performed to determine whether the amount of collagen in the alveolar wall changes with age in the lungs of non-smokers and of smokers with different types of macroscopically defined emphysema in relation to a microscopic measurement of lung structure. METHODS: Total alveolar wall collagen was measured (as hydroxyproline) in known volumes of distended lung tissue (by reverse phase high pressure liquid chromatography) in the lungs of non-smokers (n = 23) and in regions sampled away from emphysematous lesions in the lungs of 36 smokers (four with no emphysema, 13 with centriacinar emphysema (CAE), nine with panacinar emphysema (PAE), and 10 with a mixture (MIX) of both PAE and CAE). Mean lung airspace wall surface area per unit volume (AWUV) was calculated from at least six random blocks per lung and on histological sections immediately adjacent to those prepared for collagen measurement with a rapid scanning device (fast interval processor). RESULTS: In non-smokers there was no significant correlation between the amount of collagen in the alveolar wall tissue and either mean lung AWUV or increasing patient age when amounts of collagen were expressed either per unit volume of distended lung (40 mm3 sample) or per unit surface area of airspace wall tissue. Smokers without emphysema had similar amounts of collagen to non-smokers. Lungs with PAE and MIX, but not CAE alone, contained significantly more collagen than normal when expressed per unit volume of airspace wall tissue whereas all groups, including CAE, contained significantly raised amounts of collagen when expressed per unit surface area. CONCLUSIONS: There is no significant age related change in the collagen content of the lungs of non-smokers which suggests that, as AWUV is lost with age, the main collagenous framework is maintained. However, in smokers with emphysema there is a loss of airspace wall tissue in regions remote from the macroscopic lesions that is accompanied by a net increase in collagen mass. The greater accumulation of collagen in MIX lungs than in CAE lungs suggests a greater degree of structural damage, indicative of an alternative pathogenetic mechanism operating between the different types of emphysema. Our results suggest an active alveolar wall fibrosis in emphysema as a consequence of cigarette smoking. It is suggested that the definition of emphysema may require further revision to include such change. PMID- 8202901 TI - Oxygen and 99mTc-MAA shunt estimations in patients with pulmonary arteriovenous malformations: effects of changes in posture and lung volume. AB - BACKGROUND: Patients with arteriovenous malformations are routinely monitored with arterial oxygen saturation (SaO2) estimations (breathing air) from which an oxygen shunt fraction can be calculated. This simple estimation has been compared with an anatomically defined estimate of the right to left shunt using a radioisotopic method. The fall in SaO2 which occurs in patients with pulmonary arteriovenous malformations in the erect posture and at high lung volumes was used to test the ability of SaO2 alone to follow changes in right to left shunt. METHODS: Radiolabelled albumin macroaggregates (99mTc-MAA) or microspheres (MS) were injected intravenously and kidneys and lungs were imaged. The shunt fraction (QS/QTTc) in the supine position at functional residual capacity (baseline) was obtained by quantifying right kidney radioactivity. On standing or while breath holding at total lung capacity, shunt fraction was calculated from baseline QS/QTTc and from lung counts and the injected dose. Arterial oxygen saturation (SaO2) was recorded by a pulse oximeter for calculation of the oxygen shunt (QS/QTO2) (breathing air). RESULTS: In the postural study (n = 8) SaO2 decreased from a mean (SD) value of 89 (5)% supine to 80 (6)% erect, corresponding to QS/QTO2 28 (8)% and 44 (8)% respectively. QS/QTTc increased from 28.7 (10.3)% to 39 (14.3)%. In the lung volume study (n = 8) QS/QTTc increased from 16.6 (11.5)% at functional residual capacity to 23.3 (11.9)% at total lung capacity while QS/QTO2 increased from 19.5 (7.5)% to 25.9 (10.6)% respectively. When all measurements were compared for QS/QTTc% and QS/QTO2% (n = 32) the difference in the mean values was 2.5% (absolute) and the limits of agreement between the two methods were +38% to -18% (relative). In neither the postural nor the volume study did delta (QS/QTO2) reliably predict delta (QS/QTTc)%. CONCLUSIONS: In pulmonary arteriovenous malformations the simple physiological shunt calculated from SaO2 breathing air agreed well with the anatomical right to left shunt measured with 99mTc-MAA, but predicted poorly the changes in anatomical shunt induced by postural or lung volume changes. PMID- 8202902 TI - Effect of theophylline on exercise performance in patients with severe chronic obstructive pulmonary disease. AB - BACKGROUND: Theophylline is a well known bronchodilator which has been used for more than 50 years in the treatment of obstructive pulmonary diseases. In patients with severe chronic obstructive pulmonary disease whose cardiopulmonary performance is limited by their ventilatory capacity the administration of theophylline may improve exercise performance. METHODS: A randomised, placebo controlled, double blind, crossover trial was conducted in 22 patients with severe but stable disease. The patients (mean age 68 years) were studied before and after one month of placebo and one month of treatment with a sustained release preparation of theophylline administered orally. The theophylline dose was adjusted until a blood level above 55.5 mumol/l was achieved. The two treatments were administered in random order and separated by a two week washout period. After theophylline was administered for one month a mean level of 68.2 mumol/l was achieved. Pulmonary function tests, arterial blood gas measurements, maximal voluntary ventilation (MVV), and an incremental exercise test were performed before (baseline) and at the end of the first and second month of treatment. RESULTS: Pulmonary function tests showed no improvement in the flow parameters but showed an improvement in MVV after treatment with theophylline. Pulmonary gas exchange was improved after theophylline (resting arterial PO2 8.91 v 8.59 kPa, PCO2 5.38 v 5.56 kPa). The incremental exercise study showed improvement in maximal work rate (86.5 v 75.0 watts) and maximal ventilation (VEmax) (46.7 v 43.01/min). The dyspnoea index on maximal effort (VEmax/MVV), anaerobic threshold, and oxygen pulse remained unchanged. Resting and exercise heart rate were higher after theophylline. CONCLUSIONS: Theophylline improved cardiorespiratory performance in these patients with severe chronic obstructive pulmonary disease mainly by increasing the ventilatory capacity. PMID- 8202903 TI - Non-invasive beat to beat arterial blood pressure during non-REM sleep in obstructive sleep apnoea and snoring. AB - BACKGROUND: Obstructive sleep apnoea, and possibly snoring, are associated with a poorly understood increase in cardiovascular mortality which may be explained by their effects on systemic blood pressure during sleep. This study compares changes in mean blood pressure during obstructive sleep apnoea and snoring without apnoeas with those in matched control subjects during non-REM sleep. METHODS: Eighteen men with obstructive sleep apnoea, 16 men who snored without apnoeas, and 34 control subjects matched for age, sex, obesity, smoking, and alcohol intake were studied. During polysomnography non-invasive mean blood pressure (Finapres) was recorded from each cardiac cycle during non-REM sleep and averaged over a 10 minute period. This was compared with the blood pressure during 10 minutes before sleep onset. The changes in the patients' sleeping blood pressure were compared with those in their individually matched control subjects. RESULTS: Compared with the control subjects the change in mean (SD) arterial blood pressure between being awake and asleep was higher during obstructive sleep apnoea (+6.5 (9) mm Hg v-2 (6.5), difference 8.5 (11)), and the rise from wakefulness to sleep in the obstructive sleep apnoea group was itself significant. The average mean arterial pressure was not raised in those who snored without apnoeas compared with either the control subjects or during wakefulness. CONCLUSIONS: Average mean arterial pressure is higher during obstructive sleep apnoea than it is during wakefulness, while normal subjects show a fall in blood pressure at sleep onset. This sleep related rise in blood pressure may contribute to the excess cardiovascular morbidity and mortality experienced by patients with this condition. PMID- 8202904 TI - A respiratory survey in a black Johannesburg workforce. AB - BACKGROUND: The burden and determinants of airway disease in the population of southern Africa, which is currently undergoing rapid, often uncontrolled, urbanisation and industrialisation, are unknown. Previous surveys have focused on specific occupational groups and few have included women. This paper describes the respiratory status in a 30% probability sample of 206 men and 203 women drawn from an urban black Johannesburg workforce of almost 1500, all working for an educational institution. METHODS: Subjects answered a respiratory questionnaire and performed spirometric tests. Symptom rates and age and height standardised forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC%, and forced expiratory flow (FEF25-75) were analysed by gender in relation to smoking, past work exposures, past and recent respiratory conditions, and socioeconomic indicators. RESULTS: Symptom prevalence was high, bronchitic symptoms in men being related to smoking and previous occupational exposure, and in women to smoking despite the low intensity of their habit. Phlegm and wheezing were related to childhood respiratory illness in both men and women. FVC and FEV1, based on all subjects including smokers, were higher than previously reported for black residents of southern Africa. FVC was also positively related to education and job category. Higher values for ever smokers than for never smokers suggested health selection into the habit, while significant negative smoking effects were seen only on FEV1/FVC% and only in women. CONCLUSIONS: Despite the high prevalence of symptoms--some smoking related--in this urban workforce, lung function levels were higher than previously reported in African blacks, and may reflect improving socioeconomic conditions. PMID- 8202905 TI - Prevalence of asthma and risk factors among Chinese, Malay, and Indian adults in Singapore. AB - BACKGROUND: The prevalence and morbidity of asthma vary greatly among different ethnic communities and geographical locations, but the roles of environmental and genetic factors are not fully understood. The differences in prevalence of adult asthma among Chinese, Malay, and Indian ethnic groups in Singapore were examined, and the extent to which these could be explained by personal and environmental factors were investigated. METHODS: A stratified disproportionate random sample (n = 2868) of Chinese (n = 1018), Malays (n = 967), and Indians (n = 883) of both sexes was drawn from households in five public housing estates, and an interviewer administered questionnaire was used to determine cumulative and current prevalence of "physician diagnosed asthma" (symptoms with a physician diagnosis of asthma). RESULTS: Lifetime cumulative prevalence (standardised to the general population) of "physician diagnosed asthma" was 4.7% in men and 4.3% in women; 12 month period prevalences were 2.4% and 2.0%, respectively. Cumulative prevalence of asthma was significantly higher in Indians (6.6%) and Malays (6.0%) than in Chinese (3.0%); period prevalences of asthma were 4.5% in Indians, 3.3% in Malays, and 0.9% in Chinese. Ownership of cats or dogs was more frequent in Malays (15.4%) and Indians (11.2%) than in Chinese (8.8%). Rugs and carpets were also more frequently used by Malays (52.2%) and Indians (40.7%) than by Chinese (8.9%). Current smoking prevalences were higher in Malays (27.3%) than in Indians (19.4%) and Chinese (23.0%). Malays and Indians did not have higher rates of atopy (11.1% and 15.2%, respectively) than Chinese (15.4%). Adjustment for these factors in multivariate analyses reduced the greater odds of asthma in Malays and Indians, but not to a significant extent. CONCLUSIONS: There are ethnic differences in the prevalence of asthma in Singapore which are not entirely explained by differences in smoking, atopy, or other risk factors. Other unmeasured environmental factors or genetic influences are likely to account for residual differences in the prevalence of asthma. PMID- 8202906 TI - Oilseed rape and seasonal symptoms: epidemiological and environmental studies. AB - BACKGROUND: There is widespread concern that the cultivation of oilseed rape leads to seasonal epidemics of respiratory symptoms in populations living in the neighbourhood, and it has been suggested that the plant is a potent allergen. A study was therefore undertaken to determine the prevalence of seasonal symptoms in rural populations close to and far from areas of oilseed rape cultivation, and to measure the levels of allergen and other potentially harmful substances released by the crop. METHODS: Random samples of 1000 adults from the general practice populations of two villages surrounded by oilseed rape fields, and 1000 adults from one village far from such cultivation, were taken. The subjects completed a previously validated questionnaire on respiratory and other symptoms, including questions on symptom seasonality, occupation, and smoking habits. Pollen and fungal spore counts were made around fields of oilseed rape and in the villages. The chemicals released by oilseed rape were measured in the field. RESULTS: Overall, 86.8% of the subjects completed the questionnaires and the populations of the two samples were generally comparable. Spring and summer exacerbations of symptoms occurred equally in the two areas in approximately 25% of the population. There were small but significant excesses of cough, wheeze, and headaches in spring in the oilseed rape area (2.3% v 1.1%, 6.8% v 4.6%, and 4.8% v 2.8%, respectively), and cough, wheeze, and itchy skin were more prevalent in smokers. Counts of oilseed rape pollen were generally low except adjacent to fields, and counts of fungal spores were mostly higher in the rape than the non rape areas. Oilseed rape was shown to give off terpenes and these were detected close to fields. CONCLUSIONS: While it is likely that a proportion of the spring symptoms occurring in people living in close proximity to oilseed rape is caused by the plant, the excess of such symptoms is small. This, together with the low levels of pollen in the area, suggests that allergy to oilseed rape pollen is uncommon. The general prevalence of seasonal symptoms in rural areas is of interest, and a proportion of these cases is likely to be caused by factors other than allergy. Release of chemicals by plants and natural rises in summer ozone levels may be contributors. PMID- 8202907 TI - Carcinoid tumours of the thymus. AB - BACKGROUND: Carcinoid tumours of the thymus are rare. The clinical manifestations, radiographic findings, and cytological features of eight histopathologically verified thymic carcinoid tumours have been assessed. METHODS: One hundred and sixty two patients of mean age 52 (range 31-68) years with malignant mediastinal tumours were reviewed retrospectively and eight cases of thymic carcinoid were identified. Four of the eight patients were diagnosed by percutaneous ultrasound guided fine needle aspiration biopsy via a parasternal approach. RESULTS: Two patients had Cushing's syndrome at presentation and four had symptoms and signs secondary to mediastinal compression. Two were asymptomatic. Local extension of the tumour to pleura, pericardium, great vessels, phrenic nerve or regional lymph nodes, or both, were found in seven patients. Only one had the tumour confined to the thymus at diagnosis. Distant metastases were found in two patients, one to both lungs and the other in the iliac bone. Local recurrence or distant metastases developed 15-60 months after surgery in four of the five patients who underwent radical resection of the thymic tumour. Three patients died at 17 months, 34 months, and 10 years after diagnosis. The other five patients are alive at 9-51 months. CONCLUSION: Thymic carcinoid is a slow growing tumour with a poor prognosis because of its tendency to local and distant spread. Cytological examination of samples obtained by ultrasound guided fine needle aspiration may provide a useful method for diagnosis in selected patients. PMID- 8202908 TI - Efficacy of video assisted thoracoscopic lung biopsy: an historical comparison with open lung biopsy. AB - BACKGROUND: Video assisted thoracoscopic lung biopsies were compared with historical controls undergoing open lung biopsy to determine the diagnostic accuracy, effect on length of postoperative stay, and cost effectiveness of the new thoracoscopic technique. METHODS: The first 25 video assisted thoracoscopic lung biopsies performed in the Edinburgh Thoracic Unit were compared with 25 historical controls for complications, diagnostic accuracy, and length of postoperative stay. RESULTS: Statistical comparison showed equal diagnostic accuracy in both groups (96% v 92%), but mean (SD) inpatient stay was reduced in the video assisted thoracoscopic group (1.4 (0.7) days) compared with those undergoing open lung biopsy (3.1 (1.8) days). No postoperative complications were reported in the group which underwent video assisted thoracoscopic lung biopsies but three patients had postoperative complications in the open lung biopsy group. CONCLUSIONS: Video assisted thoracoscopic lung biopsy is as effective in providing histological diagnosis as is open lung biopsy. All postoperative complications were related to post thoracotomy pain and occurred only in patients undergoing open lung biopsy. Reduced postoperative disability in the video assisted thoracoscopic group decreased hospital stay, offsetting the increased cost in disposables. The overall cost of video assisted thoracoscopic and open lung biopsy was 712 pounds and 1114 pounds, respectively. PMID- 8202909 TI - Arterialised earlobe blood gas analysis: an underused technique. AB - BACKGROUND: Techniques for sampling arterialised capillary blood from the finger pulp and the earlobe were first described over two decades ago but, although close agreement between arterial values and earlobe samples has been demonstrated in normal subjects, this technique is not in common usage. METHODS: Forty patients with chronic lung disease and a wide range of arterial blood gas values were studied. Simultaneous earlobe and arterial samples were drawn with the patient at rest and analysed in the same blood gas analyser. The respiratory function laboratory staff in 50 UK hospitals with a respiratory department were telephoned and asked whether the technique was used in their hospital and the reasons, if known, for not adopting it. RESULTS: Earlobe and arterial blood gas tensions agreed closely over a wide range of values of arterial pH, PCO2 (mean difference 0.21, 95% confidence intervals -0.24 to +0.67 kPa) and PO2 (mean difference -0.17, 95% confidence intervals -1.09 to +0.75 kPa), especially at arterial PO2 values lower than 8 kPa. Of 50 UK centres surveyed 18% used the arterialised earlobe technique and 4% had plans to introduce it. Reasons for not using it were lack of knowledge in 64%, no blood gas analyser in 6%, the technique was considered inaccurate in 4%, and insufficient staff in 4%. CONCLUSIONS: Although earlobe blood gas analysis is sufficiently accurate to be reliably substituted for arterial sampling in routine clinical practice, most centres in the UK do not use the technique. The main reasons for this appear to be lack of knowledge of its existence and uncertainty over its accuracy. PMID- 8202910 TI - Community acquired lobar pneumonia in patients with HIV infection and AIDS. AB - BACKGROUND: Community acquired bacterial pneumonia is increasingly encountered in HIV infected individuals and some patients have a radiographic lobar pneumonia. METHODS: A retrospective review of clinical features, microbiological diagnosis, and outcome of community acquired lobar pneumonia was carried out in HIV positive patients admitted to a specialist unit from 1987 to 1993. RESULTS: Forty nine episodes occurred in 45 patients, all of whom were men. CD4 counts ranged widely. A bacteriological diagnosis was made in 25 episodes (51%), seven patients had more than one infective cause. The commonest pathogens were Streptococcus pneumoniae (11 episodes), Staphylococcus aureus (six), Pneumocystis carinii (three), Haemophilus influenzae (three), and Pseudomonas aeruginosa (two). Four patients died. Other complications included intrapulmonary cavitation or abscess formation (11 episodes), empyema (three), and pleural effusion (10 episodes). CONCLUSIONS: Many different infections cause community acquired lobar pneumonia in HIV positive men. Some patients have co-infections and there is a high complication rate. PMID- 8202912 TI - Intralobar bronchopulmonary sequestration: antenatal diagnosis. AB - A child with the antenatal diagnosis of pulmonary cystic adenomatoid malformation underwent thoracotomy and an intralobar bronchopulmonary sequestration was found. Histological examination of the resected specimen showed cystic adenomatoid malformation within the sequestered segment. PMID- 8202911 TI - Tropical respiratory medicine. 1. Pulmonary infections in the tropics: impact of HIV infection. PMID- 8202913 TI - Progressive tracheal and superior vena caval compression caused by benign neurofibromatosis. AB - The case history presented is of a patient with progressive tracheal and superior vena caval compression caused by a benign neurofibroma, a previously unrecognised feature of neurofibromatosis. The patient was successfully treated by surgical decompression. PMID- 8202914 TI - Asphyxia while swallowing solid food caused by bronchial compression: a variant of the pneumonectomy syndrome. AB - A 40 year old man presented with recurrent episodes of dyspnoea whilst swallowing solid food. He had undergone right pneumonectomy and thoracoplasty for recurrent pneumonias and empyema 23 years previously. Solid food boluses appeared to cause bronchial obstruction by compressing the surgically distorted left main bronchus. This is a new variant of the post pneumonectomy syndrome. PMID- 8202915 TI - False aneurysm following modified Blalock-Taussig shunt. AB - A nine month old infant with life threatening tracheal compression due to a Blalock-Taussig shunt aneurysm is described. Successful surgical management is discussed. PMID- 8202916 TI - Endobronchial nocardial infection. PMID- 8202917 TI - Fluticasone propionate v beclomethasone dipropionate (BDP) in moderate to severe asthma. PMID- 8202918 TI - Accuracy of CT appearances of fibrosing alveolitis. PMID- 8202919 TI - What research for which policy in the field of health and environment. PMID- 8202920 TI - DNA adducts in hamster and rat tracheas exposed to benzo(a)pyrene in vitro. AB - Syrian golden hamsters are much more susceptible than Wistar rats to the induction of tracheal tumors by benzo(a)pyrene (BP). In order to investigate whether this difference is reflected in the pattern of DNA-adduct induction and removal, tracheas from either species were isolated and exposed to BP (5 micrograms/ml) in organ culture. At various time-points BP-DNA adducts in the epithelial cells were quantified by 32P-postlabeling; unscheduled DNA synthesis (UDS) was determined by [3H]thymidine incorporation. In an induction-repair experiment tracheas were exposed to BP for 2 days, and cultured for another 4 days without BP. After 2 days of exposure total BP-DNA adduct levels were 10 times higher in hamster compared to rat tracheas. In hamster tracheas one major adduct was formed (95%), vs. the adduct between (+)-anti-BP-diolepoxide and deoxyguanosine (BPDE-N2dG). In rat tracheas BPDE-N2dG comprised about 60% of the total adduct level. During exposure to BP the adduct level in hamster trachea increased to 36 +/- 19 adducts/10(6) nucleotides (add/10(6) n) on day 2. Two days after removal of BP the BP-DNA adduct level had decreased to 60% of that on day 2; there was no further decrease in the BP-DNA adduct level. UDS increased during exposure to BP and decreased after removal of BP. In rats, removal of BP did not lead to a decrease in the BP-DNA adduct level, which agreed with the observed absence of UDS. In a second experiment tracheas were exposed to BP continuously for 15 days. In hamster tracheas the total BP-DNA adduct level increased from 11 +/- 0.7 add/10(6) n after 1 day of exposure to 105 +/- 2 add/10(6) n after 15 days; also UDS increased with increasing exposure until day 11. In rat tracheas no progressive increase in the BP-DNA adduct level was seen. It was concluded that the difference in trachea tumor susceptibility between hamsters and rats exposed to BP correlates with the difference between the 2 species in BP-DNA adduct kinetics in the trachea epithelial cells. PMID- 8202921 TI - Photochemical decomposition of organic compounds in water after UV-irradiation: investigation of positive mutagenic effects. AB - It should be investigated whether UV-disinfection of natural and contaminated organic substances in surface and drinking water may generate a positive mutagenic effect. Selected organic pesticides (atrazine, simazine, metobromurone, methabenzthiazurone, dichlorprop) and organic compounds naturally present in water (phenylalanine, tyrosine, polysaccharides) were examined in Ames-test (bacterial strains TA 98 and TA 100) and sister chromatid exchange (SCE)-test (V79 cells) before and after UV-irradiation. UV-irradiation with low- and high pressure mercury vapor lamps was carried out in parallel experiments. Based on results in Ames- and SCE-test a mutagenic activity was not obtained for all samples, neither before nor after UV-irradiation. PMID- 8202922 TI - Pulmonary retention and clearance of particles. AB - Research in pulmonary retention and clearance of particles intensified in the fifties in connection with interests in pneumoconiosis and in inhalation of radioactive particles, and more recently with the increased interest in the effects of environmental particles. The studies enhanced our understanding of clearance mechanisms, the various clearance pathways, the different clearance capacities of various species and the importance of other factors affecting lung clearance. Based on research in recent years, the historical concept of inert and fibrogenic particles was abandoned. It seems that particles even at surprisingly low concentrations may have negative health effects and that ultrafine particles have higher than expected toxicity when compared to similar particles of a larger size. PMID- 8202923 TI - In vivo and in vitro studies of the cellular defense system of the human lung. AB - Magnetic microparticles were used to investigate the defence system of the human lungs against foreign material. About 0.5 mg of spherical monodisperse magnetite particles were deposited in the alveolar region of the human lung by voluntary inhalation. After primary magnetization a remanent magnetic field (RMF) of the lung can be measured that allows estimation of the amount of dust retained in the lung. The decay of this RMF, called relaxation, results from a misalignment of the dipole particles due to the activity of pulmonary macrophages. This macrophage activity was characterized by a cell energy Ez. With a secondary magnetization the lung can be remagnetized by rotation of the dipole particles. This allows estimation of the intracellular viscosity and the motility of the alveolar macrophages in vivo. The macrophage cell-line J774 was used to verify the dynamic processes of the magnetic particles within the cells in vitro. In vitro and in vivo relaxation curves of polydisperse and of spherical monodisperse magnetite particles are presented. Thermal relaxation of mono-disperse and polydisperse particles within a viscous standard could be verified with the Brownian rotary diffusion model. Relaxation with monodisperse particles was double exponential in vivo as well as in vitro, suggesting that 2 different viscous compartments of the cytoplasm should be considered. Relaxation in the macrophage cell-line J774 was particle-size-dependent. PMID- 8202924 TI - Activation of promutagens by endogenous and heterologous sulfotransferases expressed in continuous cell cultures. AB - Various environmental chemicals are metabolised to chemically reactive sulfuric acid esters, which may covalently bind to cellular macromolecules and induce mutations and tumours. This activation pathway is usually not taken into account in external xenobiotic-metabolising systems used in short-term tests. We therefore analysed the abilities of cytosols from mammalian cell lines to activate benzylic alcohols (1-hydroxymethylpyrene and 9-hydroxymethylanthracene) to mutagens detectable in Salmonella typhimurium TA98. No activation was observed in cell lines which are commonly used in mutagenicity and cell transformation assays, and only low activities were found in epithelial cell lines in culture. We have therefore constructed Chinese hamster V79-derived cell lines which stably express a heterologous sulfotransferase, rat hydroxysteroid sulfotransferase a. Cytosol of these cells effectively activated 1-hydroxymethylpyrene and 9 hydroxymethylanthracene to mutagens detected in S. typhimurium. The hepatocarcinogen 6-hydroxymethylbenzo[a]pyrene induced gene mutations in sulfotransferase-expressing V79-derived cells, whereas it elicited only marginal effects in sulfotransferase-deficient control cells. The new cell lines may allow the detection of novel classes of mutagens, since some externally generated reactive sulfuric acid esters may not readily penetrate target cells due to their short life span and their ionization. PMID- 8202925 TI - Experimental data for total deposition in the respiratory tract of children. AB - Up to now only few experimental data for total deposition of inhaled aerosol particles are available for children. In this study 29 healthy children aged between 3 and 14 years volunteered for the determination of 1 micron, 2 microns and 3 microns particles for spontaneous and controlled breathing. It turns out that total deposition values for children are higher than for adults. The effect is significant for all particle sizes (Kruskal-Wallis). For the applied breathing patterns deposition decreases as a function of body height. For inhalation risk assessments the number of particles deposited per unit time (deposition rate) rather than the deposition per breath has to be taken. During spontaneous breathing at rest the deposition rate is on average higher for children than for adults. PMID- 8202926 TI - Morphologic effects of a sulfur(IV) aerosol on the nasal cavity of beagle dogs. AB - Morphologic changes were observed in nasal cavities of beagle dogs after long term exposure to a respirable sulfur(IV) aerosol at a concentration equivalent to a sulfur dioxide (SO2) concentration of 0.6 mg/m3. The changes were characterized by a thickened epithelial layer resulting from epithelial proliferation, by a loss of secretory material, and by moderate mononuclear cell infiltration. PMID- 8202927 TI - A role for cellular immunity in the induction of airway hyperresponsiveness induced by small molecular weight compounds. AB - In a murine model it was shown that during a T help-1 cell dependent immune reaction, i.e. delayed type hypersensitivity (DTH), directed against the small molecular weight compound picryl chloride (PCI), altered lung functions are induced. Skin sensitization with PCI followed by intranasal hapten challenge resulted in an increment of pulmonary resistance and airway hyperresponsiveness which are general features of asthma. Whether this is also true for low molecular weight compounds, such as toluene diisocyanate, that can induce asthmatic complaints in humans, in addition to T help-2 cell dependent immune responses, remains to be clarified in future studies. PMID- 8202928 TI - Estimation of a lifetime unit lung cancer risk for benzo(a)pyrene based on tumour rates in rats exposed to coal tar/pitch condensation aerosol. AB - Female Wistar rats were exposed to coal tar/pitch condensation (CTP) aerosol containing either 20 or 46 micrograms/m3 benzo(a)pyrene (BaP) among other polycyclic aromatic hydrocarbons (PAH) 17 h/day and 5 days/week for 10 or 20 months followed by a clean air period of up to 20 or 10 months, respectively. Based on the inhaled BaP, given as BaP exposure concentration multiplied by the total exposure time, the cumulative dose of inhaled BaP of the 4 exposure groups was 71, 142, 158 and 321 mg BaP/m3 x h and the corresponding lung tumour rates were 4.2, 33.3, 38.9 and 97.2%. There was no lung tumour in the control group. Using the US Environmental Protection Agency (EPA) linearized multistage model, the lifetime lung tumour risk for rats exposed to 1 microgram/m3 BaP as a constituent of a complex PAH mixture may be 2% or correspondingly 2 per 100,000 with a BaP concentration of 1 ng/m3. The estimation of the unit lung cancer risk for BaP based on epidemiological data from coking plants was 7-9%. PMID- 8202929 TI - Human exposure to complex mixtures of air pollutants. AB - Human exposure to complex mixtures of polycyclic organic matter (POM) from the products of incomplete combustion contribute to the potential lung cancer risk in urban areas. The most ubiquitous emission sources outdoors in populated areas are residential motor vehicles and residential heating, while environmental tobacco smoke is usually the major combustion source in indoor air. In addition to these urban combustion sources, there are industrial and municipal sources that may also have a significant impact on human exposure to carcinogenic agents due to their high DNA adduct and tumor initiating potency. This review focuses on new approaches to assess human exposure to POM using source apportionment, personal exposure monitoring, and biomarker methods. PMID- 8202930 TI - 7-Methyldeoxyguanosine as a marker of exposure to environmental methylating agents. AB - 7-Methyldeoxyguanosine (7-medG) may be a useful marker of human exposure to methylating agents at the individual level. Methods of detection, including 32P postlabeling, HPLC with electrochemical or fluorescence detection, and immunoassays, are critically summarized. These methods have been applied to the analysis of 7-medG in human samples, resulting from environmental exposure or endogenous processes. Detectable levels of adduct have been demonstrated in several tissues (liver, lung, bronchial, pancreas) and peripheral white blood cells. Studies are in progress to verify the possible use of white blood cells as a surrogate for internal organs. PMID- 8202931 TI - Comparison of chromosome aberrations and micronuclei in testing genotoxicity in humans. AB - Chromosome-type aberrations (CsA) and micronuclei (Mn) rates were compared in conventional 2-day lymphocyte cultures. In 67 healthy controls the mean rate of CsA was 0.54%, and that of Mn 2.38/1000 (median 1.66/1000). Mn were significantly correlated with age. The rate of Mn was higher in the 30 individuals with CsA > or = 1% than in the 37 subjects with no CsA. However, in 40 cadmium (Cd) workers, contrary to that found for CsA, the rates of Mn did not differ from those of the controls matched for age and smoking habits, not even in the subgroup with the highest Cd cumulative exposure index, while an age effect was evident both in the exposed and in the controls. PMID- 8202932 TI - Macromolecular adducts in the use of methyl bromide as fumigant. AB - An HPLC method for analysis of blood protein adducts of methyl bromide was developed. With this method, the alkylated amino acid S-methylcysteine can be quantified both in globin and in serum albumin. The determination of these adducts was implemented in a field study on fumigators who use methyl bromide for the control of insects, nematodes and fungi. Sister chromatid exchange (SCE) was determined in the lymphocytes of the fumigators as an additional biomonitoring parameter. Exposure of persons living in the vicinity of fumigated objects to methyl bromide has been repeatedly reported in the past. The new method for determination of blood protein adducts can be applied for evaluation of such environmental exposure. PMID- 8202933 TI - Biological monitoring of environmental exposure to polycyclic aromatic hydrocarbons; 1-hydroxypyrene in urine of people. AB - A biomarker of human exposure to chemical agents provides a valuable parameter for assessing the extent and significance of the uptake by giving a measurement that is direct and integrated over time and exposure routes. Urinary 1 hydroxypyrene is currently tested as a biomarker for the assessment of low level environmental exposure of people to polycyclic aromatic hydrocarbons (PAH). Five examples of the application of urinary 1-hydroxypyrene methodology in the assessment of environmental exposure to PAH are presented: inhalation of tobacco smoke; inhalation of urban outdoor air; windsurfers sailing on polluted water; absorption of contaminated food; exposure in an urban area with many heavy industries. The examples illustrate that the urinary 1-hydroxypyrene test is sufficiently sensitive. Urinary 1-hydroxypyrene is an effective biomarker for the assessment of human environmental exposure to PAH. PMID- 8202934 TI - Health problems of the population in different regions of the Ukraine. AB - The ecological situation in some regions of the Ukraine is critical due to the concentration of major ferrous and nonferrous metallurgy, oil refining and chemical industries, and due to the consequences of the Chernobyl accident. The health status of the whole population over the last few years has deteriorated and resulted in 1992 in a decrease in the birth-rate coefficient to 11.5 per million and an increase in the mortality rate up to 13.4 per million. The average level of life expectancy for men and women in 1991 decreased to 63.3 and 74.5 years, respectively. In 1991 the number of occupational diseases registered increased to 7958 or 3 per 10,000 of the working population, which does not reflect the real situation in the country. Major medical and biological problems of the consequences of the Chernobyl accident are restricted to the field of studying the effect of low-dose exposure and assessment of delayed stochastic effects. Until now no significant increase was registered in age-adjusted cancer, leukemia and lymphoma incidence rates among the male and female population of the most contaminated, strictly controlled territories and regions of the Ukraine in comparison with the average rate in the whole country. But the incidence of thyroid cancer in 1990 was 0.23, in 1991 0.19 and in 1992 0.35 per 100,000 children under 14 years of age. In the Ukraine the incidence of thyroid cancer in 1981-1985 did not exceed 0.04-0.06 cases per 100,000 children. PMID- 8202935 TI - Pediatric problems in upper Silesia--region of ecological disaster. AB - Increasing rates of infant mortality and child diseases in the Upper Silesian Industry Region are indices of the declared ecological disaster. The concentrations of 11 ecotoxins established in air and soil is related to the infant mortality rate, according to the degree of pollution. The percentage of infants with birthweight below 2500 g is the highest in the most polluted towns, such as Chorzow, Zabrze, Bytom. The dominating causes of infant mortality in Zabrze were infections and congenital anomalies among babies born with significantly lower birthweight. The parents of dead children have been resident for at least 15 years. In Katowice district (south-western area of Poland) there is an increasing frequency of chronic respiratory, cardiovascular, oncological and allergic diseases among children. PMID- 8202936 TI - Acute respiratory effects of summer smog in primary school children. AB - In 535 primary school children we studied the effects of exposure to summer smog on respiratory health. Baseline measurements were performed during low air pollution levels (max. 24-h concentrations of SO2, O3 and NO2 were 55, 49 and 58 micrograms/m3, respectively) consisting of lung function measurements using spirometry and the forced oscillation technique (FOT) and the prevalence of respiratory symptoms, determined by a written questionnaire. During a summer smog episode, 212 randomly chosen children were re-examined, characterised by 8-h ozone levels > 120 micrograms/m3 (max. 163 micrograms/m3) and 1-h ozone levels > 160 micrograms/m3 (max. 215 micrograms/m3). Overall, small decrements were observed in the forced expiratory volume in 1 s (FEV1), (P < 0.05) and the forced expiratory volume between 25 and 75% of the vital capacity (FEF25-75%) (P < 0.01). On the contrary, there was a statistically significant decrease in resistance parameters. No increases were observed in the prevalence of acute respiratory symptoms. In conclusion, in this study we found small inconsistent changes in lung function and no increase of respiratory symptoms after short-time exposure to moderately high ozone levels. PMID- 8202937 TI - Inhibition of phagocytosis of human macrophages induced by airborne particulates. AB - Human monocyte-derived macrophages isolated from peripheral blood were treated with different extracts of airborne particulates collected in the highly industrialized Rhine-Ruhr area. All tested extracts showed a substantial impairment of phagocytosis by inhibition of phagocytic activity as well as phagocytic capacity, while cell viability was rather well maintained. Significant reduction of phagocytosis already appeared at a concentration equivalent to extracted particulates from 3.8 m3 air. Having properties of alveolar macrophages, human monocyte-derived macrophage cultures may offer a reliable in vitro model for assessment of pulmonary toxicity by respirable pollutants. PMID- 8202938 TI - Risk assessment: good for health? AB - Risk assessment is a scientific endeavour on which risk management can be based and policy priorities can be set. Of prime importance is the choice of risk attributes and the health indicators to focus upon. Problem ranking and priority setting depend strongly on that choice. In the current risk policy of The Netherlands' Ministry of the Environment 'individual risk' is defined as the probability of dying due to one year's exposure to a certain agent or activity. If this approach is applied to the indoor environment, strong mitigation measures should be taken concerning NO2, radon and particulate matter to improve the percentage of 'healthy homes'. However, risk is more than the chance to die. Therefore some more parameters should be used to characterize the indoor environment, like chemical and biological mixtures from outside and inside and activities of inhabitants. Important health indicators like irreversible/reversible physiological effects and nuisance should be taken into account. Risk has to tell us about the possibility of health damage, about the nature of health damage and about the uncertainty in both. PMID- 8202939 TI - Ozone-induced lung toxicity: mediated by ozonides? AB - In an in vitro study a comparison was made between the cytotoxicities of a model ozonide, methyl linoleate-9,10-ozonide (MLO), and a model peroxidative agent, cumene hydroperoxide (CumOOH), by measuring the effects of both compounds on the phagocytosing capacity of rat alveolar macrophages. Toxicity as well as detoxication characteristics of the ozonide were found to be similar to those of ozone: (1) vitamin E protected the alveolar macrophages in vitro against the ozonide, (2) glutathione (GSH) depletion enhanced the sensitivity of the cells towards the ozonide and (3) the ozonide did not enhance lipid peroxidation. This also suggests that GSH depletion, followed by lipid peroxidation, does not underlie the MLO toxicity. This was supported by the differences in protection provided by vitamin C, vitamin E and GSH. Supplementation of the macrophages with vitamin C resulted in a decrease in their sensitivity towards MLO and an increase in their sensitivity towards CumOOH. Following GSH depletion the sensitivity of the cells towards CumOOH had increased more than that towards MLO. Exposure to CumOOH led to a more extensive vitamin E depletion. The results of an in vivo study on the toxicity of MLO (in the rat) largely confirmed the findings of the in vitro study: partial contributions of vitamin E and the glutathione system to the protection against MLO. PMID- 8202940 TI - Airway responses during and directly after single-time exposure to ozone. AB - Breathing pattern and lung mechanical parameters were measured in 7 female Wistar rats (ca. 200 g) during exposure to 1.0 (n = 5) or 1.3 (n = 2) ppm ozone in air for 2 h and during a 2-h post-exposure observation period. Changes in breathing pattern showed a gradual decrease from 3 to 2 Hz at constant minute ventilation during the first hour of exposure. During the second hour of exposure 6 out of 7 animals developed post-expiratory apnoea (resulting from interstitial oedema), which took about half the breathing cycle concomitant with a decrease of ca. 50% of the minute volume. The breathing pattern returned to normal at the end of the post-exposure observation period. Lung mechanical properties were determined by the forced oscillation method in the restrained, unanaesthetized, spontaneously breathing rats. Airway resistance, inertia and compliance were calculated at regular time intervals during exposure and during the observation period. Overall resistance increased significantly by a factor of 1.76 (P < 0.05); compliance decreased significantly by a factor of 3 (P < 0.05). Airway inertia showed individual increases or decreases. The mean increase (1.23) did not reach the level of significance. At the end of the exposure period the stable changes were interrupted by short-lasting periods of bronchospasms during which the airway resistance increased by a factor of 8 or more. PMID- 8202941 TI - The toxicity of air pollution in experimental animals and humans: the role of oxidative stress. AB - Nitrogen dioxide (NO2) and ozone (O3) occur throughout the world as the primary pollutants of urban air. NO2 and O3 oxidize cell membrane lipids and proteins. Inflammatory agents are elaborated from the lung either as a direct result of oxidation or as a consequence of leukocytes recruited into the lung by injury. My hypothesis is that NO2 and O3 initiate or exacerbate chronic lung disease through an inflammatory mechanism which can be reduced by supplementation with greater amounts than those required to alleviate vitamin deficiency symptoms of vitamins C (ascorbic acid) and E (alpha-tocopherol). Children, whose lungs are developing, are the most likely group to benefit from supplementation with vitamins C and E because the adverse effects of inflammation on the developing lung are likely to be greater and the time of exposure is longer than in adults. This hypothesis is in accord with current human and experimental animal data and the chemistry of O3 and NO2 toxicity, and is supported by recent ecological epidemiological studies of persons supplementing their intake of vitamins C and E. PMID- 8202943 TI - Attenuation of acute lung injury by ozone inhalation--the effect of low level pre exposure. AB - The attenuating influence of a pre-exposure of rats to a low concentration of ozone (O3) for 7 days on a subsequent O3 challenge was investigated. Effects of O3 were quantified by measuring indicators of lung permeability and inflammation in bronchoalveolar lavage fluid. The results suggest that pre-exposure to relatively low levels of O3 produces a diminished permeability response in lower airways of rats upon a following challenge with a higher level of O3. Extrapolated to human exposure situations, these data suggest that health effect evaluation of repeated exposure periods of enhanced O3 levels is rather complex and needs further investigation. PMID- 8202942 TI - Ozone-induced inflammation and altered ventilation in genetically susceptible mice: a comparison of acute and subacute exposures. AB - We have examined whether the effects of acute (2 ppm/3 h) and subacute (0.3 ppm/72 h) ozone (O3) exposures on airways are mutually predictive. Inbred C57BL/6J (susceptible) and C3H/HeJ (resistant) mice are differentially responsive to inflammation induced by the 2 exposures. Breeding experiments and cosegregation analysis indicated that 2 separate genes control inflammatory responses: Inf (acute), Inf-2 (subacute). The genetic model was also used to examine the effects of both exposures on the magnitude and pattern of breathing. Results imply that mechanisms that control susceptibility to the 2 exposures are not the same, and that one response is not necessarily predictive of the other. PMID- 8202944 TI - Biological activity of respirable industrial fibres treated to mimic residence in the lung. AB - The durability of fibres in the lung environment after deposition could be a key factor in determining whether they accumulate to a sufficient tissue dose to cause pathological change. There is a shortage of information on the relative durabilities of respirable industrial fibres of various types. We describe a strategy for assessing the ability of different fibre types to persist in the lung milieu and to retain their biological activity. This is particularly important for the development of mesothelioma, where the long latent time that characterises this disease would be expected to exclude, from culpability, fibres that are not durable. We have combined a pre-treatment step in pH 5.0 or 7.0 with an assay that relies on the ability of fibres to damage the mesothelium. The long term aim is to assess the impact that treatment in various pH solutions has on (a) fibre size/number, (b) loss of key elements, (c) the ability to damage the mesothelium. Such information should enable us to better predict the potential of fibres to cause mesothelioma. PMID- 8202945 TI - Combined influence of quartz dust, ozone and NO2 on chemotactic mobility, release of chemotactic factors and other cytokines by macrophages in vitro. AB - In this study the single as well as combined effects of quartz, ozone and nitrogen dioxide (NO2) on some immunofunctions of bovine alveolar macrophages (BAM) were investigated. After incubation with 10 micrograms/ml of particles the chemotactic response of BAM is increased nonspecifically, whereas after incubation with 100 micrograms/ml of quartz chemotaxis is specifically decreased. In addition, quartz induces tumor necrosis factor alpha (TNF-alpha) and chemokines to be released dependent on the concentration. Ozone by itself is also a very potent inducer of the release of chemokines and TNF-alpha, but in combination with ozone, quartz has not more than an additive effect. NO2 alone suppresses drastically the release of TNF-alpha. The results show that quartz, ozone and NO2 alter some immunofunctions of BAM and that by combining toxic particles such as quartz with these gases, additive but not synergistic effects might be expected. PMID- 8202946 TI - Use of asbestos, health risks and induced occupational diseases in the former East Germany. AB - In the period from 1960 to 1990 about 1.4 million tons of asbestos were imported and mainly processed into asbestos-cement products for the building industry. The production was concentrated in the former countries of Magdeburg and Dresden. In the past asbestos was primarily used as insulation and fire prevention material, etc. in the large-scale chemical industry. The asbestos was imported from the former Soviet Union, smaller amounts came from Canada. In the German Federal State of Saxony-Anhalt, approximately 600 asbestoses, almost 2700 pleural changes caused by asbestos, 843 asbestos-induced mesotheliomas and 787 bronchial and laryngeal carcinomas were recorded in the period from 1960 to 1990. A considerable percentage of the mesotheliomas are solely due to exposure to chrysotile asbestos. PMID- 8202947 TI - Lead concentration in tap-water and in blood of selected schoolchildren in southern Saxonia. AB - In a study of associations between lead in blood and in tap-water, 113 blood samples and 140 tap-water samples of schoolchildren aged 9 to 12 years were analysed. Median and maximum values of blood lead were 8.3 and 34.0 micrograms/dl and of lead in tap water 24 and 2600 micrograms/l. Lead pipes were in use in some 50% of the houses. The pH values of the tap-water varied from 5.0 to 8.1. Both factors involved, i.e., lead pipes and acidic tap-water, have to be amended in order to reduce lead exposure in some regions or locations in Germany. This necessity is emphasized by increasing evidence of adverse effects to the central nervous system in children when blood lead levels exceed 10 micrograms/dl. PMID- 8202948 TI - Method for the description of differences in the filamentous structure of the cytoskeleton in cultured cells. AB - Over the last few years in vitro cell systems have been established for toxicological investigations. These systems permit the evaluation of effects on the basis of cultured cells in order to replace animal studies. Not only qualitative assessment of cytotoxic effects, but also efforts to quantify these intracellular changes have become more and more important to objectify the results which have been obtained. The cytoskeleton, a dynamic and sensitive system, seems to be a valuable morphological parameter to gain information about the intracellular alterations of drug-influenced cells. Depending on the dose of the substance administered, the cytoskeleton shows morphological alterations in specific components, which fulfill structural as well as metabolic regulatory functions and thus provide information on possible mechanisms. Normally, microtubules as well as the intermediate filament system from 3-dimensional networks. Treatment may induce contraction or depolymerization of the filamentous proteins. These alterations, seen in immunofluorescent preparations, can be quantified by means of a 2-dimensional Fourier transformation. As there is no statistical method to compare different spectra, the spatial frequency spectrum of the Fourier components has to be transformed to a 1-dimensional array. This step is performed by measuring the optical density of localised areas in the frequency spectrum. Using this transformation it is possible to compare the Fourier spectra belonging to different treatment groups. PMID- 8202949 TI - Interactions in metal carcinogenicity. AB - The carcinogenicity and genotoxicity of cadmium, chromium, cobalt and nickel strongly depend on their chemical ligands (speciation) which modulate their bioavailability and reactivity with biochemical targets. With the exception of hexavalent chromium, carcinogenic metal compounds are only weakly genotoxic. However, the ions of the carcinogenic metals cadmium, cobalt and nickel, and also the noncarcinogenic lead, inhibit the repair of DNA damaged by direct genotoxic agents like UV irradiation and alkylating substances, thereby enhancing the effects of the latter agents. These effects are interpreted by the interference of the toxic metal ions with biochemical functions of magnesium, calcium and zinc ions. PMID- 8202950 TI - Importance of species differences in experimental pulmonary carcinogenicity of inhaled cadmium for extrapolation to humans. AB - There is sufficient evidence for pulmonary carcinogenicity of inhaled cadmium (Cd) compounds in rats whereas no such evidence was found in mice and hamsters, indicating significant species differences in the pulmonary response to inhaled Cd. We hypothesized that expression of metallothionein (MT) protein in the lung after inhalation of Cd differs between species thereby providing different degrees of sequestration of Cd and protection from its effects. Rats and mice were exposed to 100 micrograms CdCl2 aerosols/m3 for 4 weeks, and the presence of MT was determined in lung and free lung cell homogenates as well as by immunocytochemistry in lung sections up to 28 days post-exposure. Cd exposure significantly increased MT in homogenates of total lung in both species; however, no significant increase of MT in rat lung tissue after removal of free lung cells by lavage was found whereas MT was still significantly increased in lavaged mouse lung tissue throughout the post-exposure time. Histochemical analysis of lung sections revealed that mainly the epithelial cells of the bronchi, bronchioli and alveoli of Cd-exposed mice expressed MT. Baseline MT levels were also greater in the lungs of mice compared to rats. The retained Cd dose per g lung was about 2 fold greater in mice. The greater MT induction upon exposure to the same inhaled Cd concentration and the greater baseline MT levels may offer an explanation for the resistance of mice towards the pulmonary carcinogenic effect of inhaled Cd. PMID- 8202951 TI - Risk estimation of mercury intake from different sources. AB - Biological monitoring of mercury (Hg) in blood, urine and hair was performed in volunteers with amalgam fillings, in subjects who consumed fish and in Hg-exposed workers. It was found that both amalgam fillings and the consumption of fish burden the organism with Hg in the same order of magnitude. The Hg concentrations in urine in the occupationally exposed group were higher by a factor of about 100 compared to the group with amalgam fillings. No pathological changes were found in the exposed workers. It seems safe to conclude that no health-related problems from Hg are to be expected from amalgam fillings. PMID- 8202952 TI - Mechanisms in nickel genotoxicity: the significance of interactions with DNA repair. AB - Even though nickel compounds are strong carcinogens, the underlying mechanism is still unclear. In contrast to their weak mutagenic potential, they enhance the cytotoxicity and genotoxicity of UV light, X-rays and cytostatic agents like cis platinum, trans-platinum and mitomycin C. Studies in combination with UV light indicate an inhibition of DNA repair, presumably at the incision step of nucleotide excision repair. Possible reasons for repair inhibition are structural changes of the DNA or direct interactions with repair enzymes or proteins, possibly by competition with essential metal ions. PMID- 8202953 TI - Effects of UV-B on the resistance against infectious diseases. AB - It is known that ultraviolet-B light (UV-B) affects human health. In addition to deleterious effects on the skin and the eyes, such as erythema, photoageing, keratitis and cataract, UV-B is also able to impair the resistance against skin associated tumours and infections. Our data implicate that UV-B can impair the resistance against certain non-skin-associated infections in rats, such as Listeria monocytogenes, Trichinella spiralis and Ratcytomegalovirus (RCMV). Rats, infected with T. spiralis, had an increased amount of T. spiralis larvae in their carcasses after UV-B exposure in comparison to control animals, indicating that the resistance to this parasite was decreased by UV-B. Exposure to UV-B caused an increase of RCMV load in the salivary gland 26 days after infection with this virus, indicating that especially the resistance against the second generation of viruses was impaired. In L. monocytogenes-infected rats, UV-B exposure caused an increased number of bacteria in the spleen, coupled to a decreased specific response of T lymphocytes to the bacteria. We conclude that UV-B radiation may affect the resistance against several non-skin-associated infectious diseases, which is probably caused by a defect in the specific lymphocyte response to the antigen. PMID- 8202954 TI - Consumption of drinking water with high nitrate levels causes hypertrophy of the thyroid. AB - We studied the effect of nitrate contamination of drinking water on volume and function of the thyroid in human populations exposed to different nitrate levels in their drinking water. Two sets of low and medium (tap) water, respectively medium and high (well) water nitrate exposure groups were compared. Drinking of nitrate-contaminated water was dose-dependently related with 24-h urinary nitrate excretion and salivary nitrate levels. No iodine deficiency was observed in any of the nitrate exposure groups. A dose-dependent difference in the volume of the thyroid was observed between low and medium vs. high nitrate exposure groups, showing development of hypertrophy at nitrate levels exceeding 50 mg/l. An inverse relationship was established between the volume of the thyroid and serum thyroid stimulating hormone (TSH) levels. PMID- 8202955 TI - Nuclear accumulation of p53 in response to treatment with DNA-damaging agents. AB - A number of agents which damage DNA also trigger the nuclear accumulation of the tumor suppressor protein p53. Here we show the correlation with different p53 detection methods. As an example we investigated the effects of the cancer therapy drug mitomycin C on different mammalian cell lines. Our findings demonstrate that either the immunofluorescence techniques (indirect immunofluorescence staining or flow cytometric analysis) or ELISA or immunoblot assays are useful methods in detecting p53 accumulation. Simultaneously we measured DNA damage with the terminal deoxynucleotidyl transferase assay. Compatible data were obtained. Thus p53 accumulation may be used as indicator of DNA injury. PMID- 8202956 TI - Toxicity of monocyclic and polycyclic nitroaromatic compounds in a panel of mammalian test cell lines. AB - The cytotoxicity of polycyclic and monocyclic nitroarenes was tested in cell lines V79/NH, H4IIEC3/G-, 5L and BWI-J, which are distinguished by their specific expression of xenobiotic metabolizing enzymes. The results show that polycyclic nitroarenes differentially affect the test cell lines suggesting that some compounds, such as 1,3-dinitropyrene, are activated by cytochrome P4501A1, others, such as 1,6-dinitropyrene, by reductase(s) and acetyltransferase. No such cell specific responses were seen for 13 monocyclic nitroarenes tested. This group of chemicals apparently is activated by an enzyme(s) other than the polycyclic nitroarenes tested. PMID- 8202957 TI - Neuroendocrine phenotype differentiation in a hamster lung epithelial cell line under low oxygen pressure or after transformation by diethylnitrosamine. AB - Oxygen pressure as low as 5% in the gas phase or 87 mmHg in the liquid phase induced various neuroendocrine cell (NEC) phenotypes in more than 80% of cells of a cloned fetal Syrian hamster lung epithelial cell line (M3E3/C3). Further, cells from a number of colonies transformed in an anchorage-independent manner by diethylnitrosamine (DEN) demonstrated a NEC phenotype. Since the cell line used is of a pluripotent stem cell type, both hypoxia and DEN appear to possess a potency for NEC phenotype induction. PMID- 8202958 TI - Multistage carcinogenesis utilizing human genital cells and human papillomaviruses. AB - The preponderance of evidence indicates that a subset of human papillomaviruses are important etiological agents for cervical cancer. However, the necessity of other agents as well as cellular events is recognized because not all women with papillomaviruses develop cancer. Therefore, the exact role of papillomaviruses in the multistage carcinogenesis process is unclear. Regulation of specific viral genes is important to the malignant process. The current study demonstrates that human herpesvirus-6, another ubiquitous virus, can infect genital epithelial cells and upregulate the expression of relevant papillomavirus genes. Thus, it can be considered a cofactor for cancer. PMID- 8202959 TI - Effects of outdoor and indoor airborne particulate matter on thyroid hormone and vitamin A metabolism. AB - Vitamin A is an important regulator of normal epithelial differentiation and proliferation and might act in the promotion phase of carcinogenesis. Vitamin A and thyroid hormone metabolism are linked by a common plasma carrier protein transthyretin (TTR). Results indicated that extracts of outdoor and indoor airborne particulate matter (APM), originating from different pollution sources, significantly interfered with thyroxine (T4) binding to TTR. The neutral fraction accounted for most of the inhibitory activity. Polycyclic aromatic hydrocarbons and nitrated derivatives were not responsible for the activity of the neural fraction. A single treatment of rats with an outdoor and cigarette smoke APM extract depleted plasma T4 and triiodothyronine levels and increased plasma retinol levels, while liver and lung retinol levels were depleted. The studies show that APM extracts have the potency to interfere with thyroid hormone metabolism both in vitro and in vivo and to deplete lung vitamin A in vivo. PMID- 8202960 TI - Airborne mutagens and carcinogens from cooking and other food preparation processes. AB - The common food preparation processes, frying, broiling and baking, can give rise to air pollutants that are known to be mutagenic and carcinogenic in animal tests. A large number of persons can be exposed to such fumes as cooking is performed in most households and in many commercial enterprises. Additional studies on the emissions from these processes and exposure measurements are needed. Epidemiological studies on occupationally-exposed cooks and bakers with respect to cancer are equivocal. PMID- 8202961 TI - Inhibition of gap-junctional intercellular communication by outdoor and indoor airborne particulate matter. AB - The inhibition of gap-junctional intercellular communication (GJIC) by different airborne particulate matter (APM) extracts was tested in V79 cells and in primary cultures of alveolar type II cells. The results show that extracts of APM were able to inhibit GJIC in V79 and in alveolar type II cells at non-cytotoxic doses. Chemical fractionation of extracts showed that the neutral fractions accounted for most of the inhibitory activity on GJIC. The activities of basic and acid fractions was less than 5% of the total activity. Polycyclic aromatic hydrocarbons and nitrated derivatives are unlikely to be responsible for the activity of the neutral fractions, because several representatives of these compounds failed to inhibit GJIC. Taken together, these results suggest that extracts of APM, in addition to the genotoxic activity that has been known for many years, also have a tumor promoting activity. PMID- 8202962 TI - Comparative genotoxicity testing of airborne particulates using rodent tracheal epithelial cells and human lymphocytes in vitro. AB - In our study samples of airborne particulates were collected in the heavily industrialized Rhine-Ruhr region utilizing a high volume sampler HVS 150 (Strohlein Instruments) equipped with glass fibre filters. Chemical substances were extracted from filters with dichloromethane and quantitatively transferred to dimethyl sulfoxide (DMSO) for tissue culture experiments. For detection of genotoxicity of extract of airborne particulates we utilized as a sensitive bioassay the induction of 'sister chromatid exchanges' (SCE) in cultures of human lymphocytes and of tracheal epithelial cells of the Syrian golden hamster. The extract of airborne particulates was added in various concentrations to cell cultures of human lymphocytes and hamster tracheal epithelial cells in presence of bromodeoxyuridine for 72 or 48 h, the last 3 h in presence of demecolcine or nocodazole, respectively. Extract of airborne particulates led in both test systems--human lymphocytes and tracheal epithelial cells of the hamster--to a dose-dependent, highly significant induction of 'sister chromatid exchanges'. Very low quantities of substances corresponding to airborne particulates from less than 1 m3 air were highly effective in both cell systems. In comparison, tracheal epithelial cells of the Syrian golden hamster revealed a higher sensitivity showing a steeper increase of 'sister chromatid exchanges' than human lymphocytes. PMID- 8202963 TI - Ticlopidine, trials, and torture. PMID- 8202964 TI - Effective treatment of poststroke depression with the selective serotonin reuptake inhibitor citalopram. AB - BACKGROUND AND PURPOSE: The aim of the study was to investigate the efficacy and safety of the selective serotonin reuptake inhibitor citalopram in treating poststroke depression, since available treatments are usually poorly tolerated. METHODS: A 6-week double-blind, placebo-controlled trial was undertaken. Diagnosis and outcome were determined using the Hamilton Depression Scale, and unwanted effects were measured using the UKU side effect rating scale. Sixty-six consecutive depressed patients from an unselected population of 285 stroke patients aged 25 to 80 years entered the trial 2 to 52 weeks after stroke. They were assigned to equally sized treatment and placebo groups. The initial level of depression was comparable in the two groups (mean baseline Hamilton Depression scores, 19.4 and 18.9, respectively). Demographic parameters were also comparable in the two groups. RESULTS: Significantly greater improvement was seen in patients treated with citalopram (10 to 40 mg/d) for 3 and 6 weeks, both when including all patients (intention-to-treat analysis, P < .05) and excluding patients who dropped out during the first 3 weeks (efficacy analysis, P < .005). Half of the 28 patients who entered the trial 2 to 6 weeks after stroke recovered within 1 month, independent of the treatment given. This indicates a high degree of spontaneous recovery in the early phase after stroke. In contrast, recovery was infrequent in placebo group patients who became depressed 7 weeks or more after stroke. No serious side effects related to the treatment were detected; those present were mild and usually transient. CONCLUSIONS: This trial demonstrates that the selective serotonin reuptake inhibitor citalopram offers an advantageous new treatment of poststroke depression that is both safe and effective. PMID- 8202965 TI - Pattern of activation of the hypothalamic-pituitary-adrenal axis in acute stroke. Relation to acute confusional state, extent of brain damage, and clinical outcome. AB - BACKGROUND AND PURPOSE: The aim of this study was to characterize the response of the hypothalamic-pituitary-adrenal system in the first hours of ischemic stroke and to relate its extent to the occurrence of acute confusional state, volume of brain damage, and clinical outcome. METHODS: The secretion of corticotropin (adrenocorticotropic hormone [ACTH]) and cortisol was studied in 23 patients by determinations at hours 4, 6, 8, 10, and 14 and days 1, 3, 5, and 7 after onset of symptoms. Acute confusional state (DSM-III-R criteria), extent of lesion (volumetry of computed tomographic scans), and neurological and functional outcome (Scandinavian Stroke Scale, Barthel Index scores) were assessed. RESULTS: The massive neuroendocrine response observed consisted of an initial phase with concomitantly increased levels of ACTH and cortisol and a second phase with decreased levels of ACTH while high concentrations of cortisol persisted. Initial levels of ACTH but not cortisol were significantly increased in patients with acute confusional state and significantly correlated with volume of brain lesion and neurological and functional outcome. CONCLUSIONS: An early and persisting activation of the hypothalamic-pituitary-adrenal axis was observed in relation to severity of disease. Its characteristic biphasic pattern suggests an initial central stimulation of release of ACTH followed by feedback suppression concomitant with an increased susceptibility of the adrenal gland. Because these hormones are known to exacerbate hypoxic injury to neurons, their massive release in hyperacute stroke may increase the extent of brain damage. PMID- 8202966 TI - Cognitive correlates of ventricular enlargement and cerebral white matter lesions on magnetic resonance imaging. The Rotterdam Study. AB - BACKGROUND AND PURPOSE: Ventricular enlargement and white matter lesions are frequent findings on cerebral magnetic resonance imaging scans of elderly subjects. In demented subjects they seem related to the severity of the dementia, but in nondemented subjects their clinical significance is less clear. We investigated the relation of size of the lateral ventricles and white matter lesions with cognitive function in a population-based random sample of nondemented elderly persons. METHODS: The study population consisted of 90 subjects, aged 65 to 84 years, who were randomly selected from the cohort of the Rotterdam Study, and who were not demented. The presence of white matter lesions and the ventricle-to-brain ratio were assessed on magnetic resonance scans. Participants were tested with a neuropsychological battery that covered a broad range of cognitive functions. RESULTS: Ventricular enlargement and white matter lesions were both and independently associated with poorer performance on all tests. After adjustment for age and sex, ventricular enlargement was significantly associated with worse scores on tests assessing global cognitive function (Mini-Mental State Examination, P = .02; Groninger Intelligence Test, P = .01), memory (Word List Learning delayed recall, P = .03), and executive control functions (Stroop part II, P = .02; Trial Making Test B, P < .01); for white matter lesions the differences were significant for tests measuring executive control functions and mental speed (Trail Making Test A and B, P = .01 and P < .01, respectively; verbal fluency, P = .01), and memory (Word List Learning delayed recall, P = .04). CONCLUSIONS: This study suggests that white matter lesions are primarily related to impairment of subcorticofrontal functions, whereas enlargement of the lateral ventricles is associated with disturbances of cortical functions as well. PMID- 8202967 TI - Multicenter review of preoperative risk factors for carotid endarterectomy in patients with ipsilateral symptoms. AB - BACKGROUND AND PURPOSE: Randomized clinical trials have shown that carotid endarterectomy decreases the risk of subsequent stroke in patients with high grade carotid stenosis and ipsilateral transient ischemic attack or minor stroke. The benefit of surgery is highly dependent on surgical risk. We previously found that patients with ipsilateral hemispheric symptoms were at greater risk of carotid endarterectomy complications compared with those who were asymptomatic or had nonipsilateral symptoms. The goals of the present study were (1) to identify preoperative clinical factors that may increase the risk of complications after carotid endarterectomy in patients with ipsilateral hemispheric symptoms and (2) to develop a risk index based on this patient-level data. METHODS: Records from 1160 carotid endarterectomies performed at 12 academic medical centers composed the primary data set. Hospital charts for the admission during which carotid endarterectomy was performed were systematically reviewed by abstractors using a defined protocol. The present analysis was carried out on data from the subset of patients who had carotid endarterectomy for ipsilateral hemispheric symptoms. Candidate variables were identified based on univariate Fisher's exact tests or chi 2 tests. A risk index was then developed using those variables with a greater than 90% probability of being associated with adverse outcomes. RESULTS: Of the 697 patients with ipsilateral symptoms, 8.5% had either stroke, myocardial infarction, or died during the postoperative period of hospitalization. Those over the age of 75 had a greater risk of myocardial infarction (6.6% versus 2.3%, P = .024) but not of stroke or death (P > .10). The overall frequencies of adverse outcomes were also higher in the 5 patients with complete ipsilateral carotid occlusions (40% versus 8.2%, P < .01), the 28 patients with ipsilateral intraluminal thrombus (17.9% versus 8.1%, P = .07), and the 65 patients with ipsilateral carotid siphon stenosis (13.9% versus 7.9%, P = .10). There were no differences in adverse outcomes among those with different degrees of ipsilateral stenosis (30% to 49%, 50% to 69%, and 70% to 99%). Adverse outcome rates were similar regardless of the type of symptom (transient ischemic attack, recent ipsilateral minor stroke, remote ipsilateral minor stroke). There were no significant differences in adverse outcome rates based on sex, race, history of angina, recent myocardial infarction, congestive heart failure, chronic obstructive pulmonary disease, hypertension, degree of stenosis of the contralateral carotid artery, or presence of ulceration in the ipsilateral artery (Fisher's exact tests, P > .10). A count of variables with greater than 90% probability of being associated with adverse outcomes (age > or = 75 years or angiographic evidence of ipsilateral carotid occlusion, stenosis in the region of the carotid siphon, or intraluminal thrombus) was used to form a simple risk index. "High-risk" patients (one or more risk factors) had more than two times the risk of complications compared with "low-risk" patients who had no risk factors (odds ratio, 2.18; 95% confidence interval, 1.25 to 3.81). CONCLUSIONS: Certain preoperative clinical variables may place patients with ipsilateral symptoms at greater risk of perioperative complications after carotid endarterectomy. Prospective validation of a simple risk index would provide an additional method for assessing preoperative risk in endarterectomy candidates. PMID- 8202968 TI - Baseline silent cerebral infarction in the Asymptomatic Carotid Atherosclerosis Study. AB - BACKGROUND AND PURPOSE: In a group of patients with high-grade asymptomatic carotid artery stenosis, we prospectively determined the prevalence and radiological characteristics of clinically asymptomatic brain infarction evident on computed tomography. Risk factors and extent of carotid disease were also determined. METHODS: Patients randomized into the Asymptomatic Carotid Atherosclerosis Study (ACAS) underwent a neurological history, a detailed stroke/transient ischemic attack questionnaire, and a detailed neurological examination. Computed tomography scans were examined by standardized criteria developed as part of a quality-control program supervised by a neuroradiologist. The presence, location, and size of all cerebral infarctions evident by computed tomography were determined. RESULTS: Among 1132 patients, 848 had no history of stroke or transient ischemic attack. One hundred twenty-six patients (15%) had a silent infarct; 95 (11%) had one, 24 (3%) had two, and 7 (1%) had three or more infarcts. The infarct size was small and deep for 117 patients (72%), less than one-half lobe for 45 (28%), and one-half to less than one lobe for 1 (0.5%). The silent infarcts were evenly distributed ipsilaterally and contralaterally to the study artery but were significantly more frequent in the right hemisphere (P < .05). Factors associated with silent infarction were abnormal gait (P < .001), abnormal deep tendon reflexes or plantar responses (P = .038), but not degree of carotid stenosis. Silent infarction was less frequent among this totally asymptomatic cohort (15%) compared with those with transient ischemic attacks (34/139, 25%; P < .001). CONCLUSIONS: Silent infarction in the setting of asymptomatic carotid stenosis is not uncommon, but silent infarctions are rarely sizable. The clinical significance of silent cerebral infarction in patients with asymptomatic carotid artery stenosis has yet to be established. PMID- 8202969 TI - Angiographic detection of carotid plaque ulceration. Comparison with surgical observations in a multicenter study. North American Symptomatic Carotid Endarterectomy Trial. AB - BACKGROUND AND PURPOSE: Carotid plaque ulceration is used as one of the determinants in deciding which patients should be submitted to carotid endarterectomy. Uncertainties about its importance persist. Its detection by angiography is an important consideration. METHODS: The detection of ulceration by angiography was compared with observations during endarterectomy in the first 500 patients recruited into the North American Symptomatic Carotid Endarterectomy Trial. This represents the first multicenter compilation of data on this subject and the largest series of patients with both arteriographic and direct surgical observation. RESULTS: Sensitivity and specificity of detecting ulcerated plaques were 45.9% and 74.1%, respectively. The positive predictive value of identifying an ulcer was 71.8%. These results remained unchanged with differing degrees of carotid stenosis and were confirmed by analyses based on receiver operating characteristic (ROC) methodology. The area under the ROC curve (Az) was estimated to be 0.61 (95% confidence interval, 0.55 to 0.67). CONCLUSIONS: These observations from a multicenter study confirm that little agreement exists between angiography and surgical observation in detecting carotid plaque ulceration. PMID- 8202970 TI - Carotid plaque, aging, and risk factors. A study of 457 subjects. AB - BACKGROUND AND PURPOSE: The aim of this study was to assess the prevalence of extracranial carotid artery atherosclerosis and its relation to principal cardiovascular risk factors at different ages in a sample of the general population. METHODS: B-mode ultrasonography was used to investigate the carotid district in 457 subjects (231 men and 226 women; mean age, 55.4 +/- 18.7 years; range, 18 to 97 years) in the metropolitan area. The ultrasonographic findings were then related to risk factors. RESULTS: Carotid plaques were found in 178 subjects (38.9%). The prevalence of atherosclerosis, number of plaques, and severity of stenosis were observed to increase with age. Age (P < .0001), cigarette smoking (P < .0001), male sex (P < .001), total cholesterol (P < .05), and, inversely, the ratio of high-density lipoprotein cholesterol to total cholesterol (P < .05) were found to be independently associated with carotid atherosclerosis. Stratified analysis by sex and age showed effect modifications by age on cigarette smoking, total cholesterol, and the ratio of high-density lipoprotein cholesterol to total cholesterol. After multivariate analysis including interaction terms, cigarette smoking and cholesterol levels were not longer found to be associated with carotid atherosclerosis in elderly subjects. Age (P < .01), total cholesterol (P < .05), and diabetes (P < .05) were positively related to the severity of vascular narrowing. CONCLUSIONS: There is a high prevalence of asymptomatic carotid atherosclerosis in the general population, particularly among the very old. The association between risk factors and carotid atherosclerosis is less pronounced in the elderly than in younger subjects. PMID- 8202971 TI - Ganglioside GM1 in acute ischemic stroke. The SASS Trial. AB - BACKGROUND AND PURPOSE: We sought to assess the safety and efficacy of ganglioside GM1 in acute (< or = 48 hours), anterior circulation ischemic stroke. METHODS: We screened more than 5000 patients at 13 centers in a randomized, double-blind, placebo-controlled, parallel-treatment, clinical trial and enrolled 287 patients. They received 100 mg GM1 or placebo intramuscularly daily for 28 days and were evaluated regularly for 84 days. Number of deaths, the Toronto Stroke Scale, and the Barthel Index were primary outcomes; improvements on the Fugl-Meyer Scale and on a neuropsychological battery were secondary outcomes. RESULTS: The groups were balanced for severity, side of stroke, age, sex, race, years of schooling, prior illness, and depression scores. Analyzable data were available on 275 patients; 217 patients completed the trial. Protocol-specified primary and secondary outcome measures showed no significant difference between treatment arms. However, improvement from baseline in the motor component of the Toronto Stroke Scale favored the GM1-treated group at day 28 when GM1 treatment stopped (P = .020); at day 84, the difference still favored the GM1-treated group (P = .057). All 10 components of the Barthel Index, the Fugl-Meyer Scale, and four of the five tests in the neuropsychological battery also favored the GM1 group. Adverse experiences were similar in the two groups. CONCLUSIONS: GM1 is safe. However, since only certain post hoc tests showed statistically significant differences or trends favoring GM1, another clinical trial is needed to demonstrate efficacy. PMID- 8202972 TI - Cost-effectiveness of ticlopidine in preventing stroke in high-risk patients. AB - BACKGROUND: Ticlopidine, an antiplatelet agent, when compared with aspirin has been found to reduce the risk of stroke in high-risk patients, ie, those with recent transient ischemic attack, reversible ischemic neurological deficit, amaurosis fugax, or minor stroke. Its cost-effectiveness in such use, however, is unknown. METHODS: We developed a model of primary stroke prevention in which a hypothetical cohort of 100 high-risk men and women 65 years of age was assumed to receive either ticlopidine (500 mg daily) or aspirin (1300 mg daily). Using published data, we estimated lifetime incidence of stroke, life expectancy (unadjusted and adjusted for changes in quality of life), and lifetime medical care costs associated with each therapy. RESULTS: Patients who receive ticlopidine would experience two fewer initial strokes per hundred than those treated with aspirin. Life expectancy would be extended by approximately one-half month, and lifetime medical care costs (discounted at 5%) would increase by about $2300. The cost-effectiveness of ticlopidine, compared with aspirin, is estimated to range from $31,200 to $55,500 per quality-adjusted life-year gained as the utility of life after nonfatal stroke is assumed to vary from 0.75 to 0.95. CONCLUSIONS: Ticlopidine therapy to prevent stroke in high-risk patients is cost effective by current standards of medical practice. PMID- 8202974 TI - Stroke incidence and mortality in rural and urban Shanghai from 1984 through 1991. Findings from a community-based registry. AB - BACKGROUND: Mortality from stroke has declined in many countries. This decline may result from a fall in incidence of stroke or a decrease in case fatality from stroke. The present study was conducted to investigate the temporal trends of incidence rate, mortality rate, and case fatality of stroke in an urban and rural Chinese population. METHODS: A community-based registry study was established in 1983 in defined rural and urban areas of Shanghai with a population aged 35 to 74 years of approximately 86,000 subjects, adhering to the methods and definitions of the World Health Organization MONICA protocol. All stroke events occurring in the population aged 35 to 74 years in these areas were registered by a special three-level case-registration system. RESULTS: From 1984 through 1991, 1391 stroke cases were identified. No significant change in the incidence rate of stroke was observed from 1984 through 1991 in men and women living in rural and urban areas. Age-standardized mortality rates (per 100,000 person years) of stroke declined significantly during this period, except for rural women. The annual changes and 95% confidence intervals of age-standardized mortality rates were: for rural men -4.6% (-5.4, -3.9), for rural women -0.6% (-1.6, 0.5), for urban men -2.5% (-3.5, -1.6), and for urban women -4.7% (-5.2, -4.2). A significant decrease in case fatality from stroke from 1984 through 1991 was found among men living in rural areas (from 62.4% to 46.0%) and among women living in urban areas (from 48.4% to 33.3%). Overall case fatality, however, showed a nonsignificant decline over time. CONCLUSIONS: We observed a decline in stroke mortality rate in a rural and urban Chinese population. No significant changes in stroke incidence were found in this study, whereas case fatality appeared to have decreased, in particular among men living in rural areas and women living in urban areas. PMID- 8202973 TI - Non-insulin-dependent diabetes and its metabolic control are important predictors of stroke in elderly subjects. AB - BACKGROUND AND PURPOSE: Non-insulin-dependent diabetes mellitus (NIDDM) is a major risk factor for stroke in the middle-aged population, but few prospective population-based studies are available in the elderly. Moreover, the importance of metabolic control and the duration of diabetes in diabetic subjects has remained controversial. There are no previous studies on association of insulin with the risk of stroke. The present study examined whether NIDDM, its metabolic control and duration, and insulin level predict stroke. METHODS: We measured cardiovascular risk factors including glucose tolerance, plasma insulin, and glycosylated hemoglobin A1c in a Finnish cohort of 1298 subjects aged 65 to 74 years and investigated the impact of these risk factors on the incidence of both fatal and nonfatal stroke during 3.5 years of follow-up. RESULTS: Of 1298 subjects participating in the baseline study, 1069 did not have diabetes and 229 had NIDDM. During the 3.5-year follow-up, 3.4% (n = 36) of nondiabetic subjects and 6.1% (n = 14) of NIDDM subjects had a nonfatal or fatal stroke. The incidence of stroke was significantly higher in diabetic women compared with nondiabetic women (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.65 to 3.06). In contrast, the risk of stroke was not significantly higher in diabetic men than in nondiabetic men (OR, 1.36; 95% CI, 0.44 to 4.18). In multivariate logistic regression analyses including all study subjects, fasting and 2-hour glucose (P < .01 and P < .05, respectively), glycosylated hemoglobin A1c (P < .01), atrial fibrillation (P < .05), hypertension (P < .05), and previous stroke (P < .01) predicted stroke events. In diabetic subjects, fasting and 2-hour glucose (P < .01 and P < .05, respectively), glycosylated hemoglobin A1c (P < .05), the duration of diabetes (P < .05), and atrial fibrillation (P < .05) were the baseline variables predicting stroke events. Finally, fasting insulin (P < .05), hypertension (P < .05), and previous stroke (P < .01) were associated with stroke incidence in nondiabetic subjects. CONCLUSIONS: Our 3.5-year follow-up study provides evidence that NIDDM, its metabolic control, and the duration of diabetes are important predictors of stroke in elderly subjects, particularly in women. Moreover, fasting insulin level appears to be a risk factor for stroke in elderly nondiabetic subjects. PMID- 8202975 TI - Trends in stroke incidence and mortality in Hawaiian Japanese men. AB - BACKGROUND AND PURPOSE: Vital statistics show a sharp decline in stroke mortality since the late 1960s. It is not clear whether this has been associated with a decline in stroke incidence. METHODS: Since 1966 the Honolulu Heart Program has monitored the incidence and mortality of coronary heart disease and stroke in a target population of 11,136 men of Japanese ancestry living on Oahu. Trends were analyzed from January 1, 1969, through December 31, 1988. RESULTS: Of 7893 men aged 45 to 68 years and free of stroke at entry examination, 530 developed first episodes of stroke in the period 1969 to 1988 (389 cases of thromboembolic stroke, 124 cases of hemorrhagic stroke, and 17 cases of stroke of unknown type). Age-adjusted annual stroke incidence declined from 5.1 per 1000 person-years in 1969 to 1972 to 2.4 in 1985 to 1988. The incidences of thromboembolic stroke, hemorrhagic stroke, and total stroke decreased 3.5%, 4.2%, and 4.4% per year, respectively. The 1-month case-fatality rates for thromboembolic stroke decreased moderately; those for hemorrhagic stroke fell dramatically. CONCLUSIONS: These findings suggest that the decline in stroke mortality in the past two or three decades results from a decline in both incidence rates and early case-fatality rates in thromboembolic and hemorrhagic stroke and stroke of unknown type. The decreases may be related to changes in risk factors, such as the decline in blood pressure and the decrease in cigarette smoking, as well as improvements in diagnosis and treatment. PMID- 8202976 TI - Sensory stimulation promotes normalization of postural control after stroke. AB - BACKGROUND AND PURPOSE: In a randomized study of hemiparetic stroke patients with a median age of 75 years, functional recovery was significantly better in those who received additional sensory stimulation (n = 38), including electrostimulation, than in control patients (n = 40) given the same physiotherapy and occupational therapy; group differences for balance, mobility, and activities of daily living were significant. The present study was designed to investigate postural control in patients who survived more than 2 years after stroke onset. METHODS: The 48 survivors (mean, 2.7 years; range, 2.0 to 3.8 years), 22 from the treatment group and 26 from the control group, were compared with 23 age-matched healthy subjects. Subjects were perturbed by vibrators applied to calf muscles or with galvanic vestibular stimulation. We evaluated postural control in terms of sway variances or sway velocities and the dynamics of postural control as a feedback system using system identification with a model previously validated for human postural control. RESULTS: Significantly more patients of the treatment group than of the control group maintained stance during perturbations (P < .01). Among patients capable of maintaining stance during perturbation, the control patients were characterized by significant divergence from normal values in two of the three characteristic parameters of dynamic postural control (ie, swiftness and stiffness; P < .05) compared with the treatment subgroup or age-matched subjects. CONCLUSIONS: The course of sensory stimulation enhanced recovery of postural function, an enhancement still significant 2 years after the lesion and treatment. The differences and near normalization of characteristic parameters of dynamic postural control among treated patients suggest that improved recovery after sensory stimulation may be achieved by patients regaining normal or near normal dynamics of human postural control. PMID- 8202977 TI - Similar motor recovery of upper and lower extremities after stroke. AB - BACKGROUND AND PURPOSE: This study examined the validity of the clinical tenet that poststroke recovery of the upper extremity is less rapid and complete than poststroke recovery of the lower extremity. Previous studies comparing upper and lower extremity recovery have evaluated disability rather than motor impairment. Individuals with lower extremity impairments may be more functional and appear less disabled than individuals with upper extremity impairments. Function of the upper extremity requires finer motor control, for which the patient can less readily compensate. Therefore, impairments and disability would predictably be more highly correlated in this area. We tested the hypothesis that upper and lower extremity motor recovery are similar. METHODS: The 95 patients selected for this study were enrolled in the Durham County Stroke Study and had been diagnosed with anterior circulation ischemic stroke. Each subject received Fugl-Meyer assessments within 24 hours of admission and then 5, 30, 90, and 180 days after stroke. We used these assessments to compare the time course and patterns of motor function of the upper and lower extremities. RESULTS: Repeated-measures ANOVA revealed that percent maximal motor recovery was significantly (P < .001) affected by time after stroke but not by extremity (upper extremity versus lower extremity) (P = .32). When stroke severity level is controlled, the upper and lower extremities continue to show no difference in percent motor recovery (P = .19). CONCLUSIONS: In patients with anterior circulation ischemic stroke, the severity of motor impairment and the patterns of motor recovery are similar for the upper and lower extremities. The most rapid recovery for both extremities occurs within 30 days. PMID- 8202978 TI - Rehabilitation of walking with electromyographic biofeedback in foot-drop after stroke. AB - BACKGROUND AND PURPOSE: Alterations of gait cycle and foot-drop on the paretic limb are characteristic of stroke patients. Electromyographic biofeedback treatment has been used in rehabilitation of walking, but results are controversial. We performed gait analysis to evaluate the efficacy of electromyographic biofeedback compared with physical therapy. METHODS: Sixteen patients with ischemic stroke were enrolled in the study. The experimental group (4 men, 4 women) received electromyographic biofeedback treatment together with physical therapy. The control group (5 men, 3 women) was treated with physical therapy only. Clinical and functional evaluations before and after treatment were performed using Canadian Neurological, Adams, Ashworth, Basmajian, and Barthel Index scales. Computerized gait analysis was performed in all patients. RESULTS: Electromyographic biofeedback patients showed significantly increased scores on the Adams scale (P < .05) and Basmajian scale (P < .01). Gait analysis in this group showed a recovery of foot-drop in the swing phase (P < .02) after training. CONCLUSIONS: Our data confirm that the electromyographic biofeedback technique increases muscle strength and improves recovery of functional locomotion in patients with hemiparesis and foot-drop after cerebral ischemia. PMID- 8202980 TI - Internal carotid artery redundancy is significantly associated with dissection. AB - BACKGROUND AND PURPOSE: Redundant internal carotid arteries have been considered a risk factor in tonsillectomy, adenoidectomy, and surgical treatment of peritonsillar abscess and also a potentially treatable cause of stroke. However, an association between internal carotid artery redundancy and spontaneous dissection has not yet been clearly demonstrated. METHODS: We reviewed, for spontaneous carotid artery dissection, records of all patients admitted to our institution during the period from 1986 through 1992 with the diagnosis of stroke or transient ischemic attack. We also reviewed 108 percutaneous cerebral arteriograms performed between September 1992 and December 1992 for presence of carotid artery redundancies. RESULTS: Thirteen patients exhibited spontaneous dissection. Of these, 8 of 13 (62%) patients and 13 of 20 (65%) internal carotid arteries, viewed to the siphon, had significant redundancies, kinks, coils, or loops. Of 108 consecutive arteriograms of patients without dissection, in which 187 internal carotid arteries were viewed to the siphon, there were 20 (19%) patients and 22 (12%) of 187 vessels with significant redundancy. Five patients in the dissection group and 2 in the nondissection group had bilateral internal carotid artery redundancy (P = .0019 and P = .0001, respectively). CONCLUSIONS: We found a significant correlation between internal carotid artery redundancy and dissection, particularly if redundancy is present bilaterally. PMID- 8202979 TI - Patterns of cerebrovascular reactivity in patients with unilateral asymptomatic carotid artery stenosis. AB - BACKGROUND AND PURPOSE: Intracranial hemodynamic status varies in patients with unilateral significant carotid artery stenosis. It ranges from normal, because of sufficient collaterals, to poor, because of a severely reduced blood supply that puts the patient at an increased risk of stroke or cerebral ischemia. The present study examined patterns of abnormal cerebrovascular hemodynamics in patients with asymptomatic carotid artery stenosis. METHODS: The CO2 reactivity of the cerebral resistance index (CRi) and of mean blood flow velocity (vmean) was determined via transcranial Doppler sonography in 91 patients with unilateral high-grade to threadlike carotid artery stenosis and in 37 control subjects. The interhemispheric asymmetry of CRi reactivity of the control group was used to differentiate between normal and abnormal findings. RESULTS: We found that 64.8% of the patients demonstrated normal CRi asymmetry with comparable CRi reactivity (ipsilateral, 4.42 +/- 0.44 %CRi/vol%CO2; contralateral, 4.51 +/- 0.39 %CRi/vol%CO2) and vmean reactivity (ipsilateral, 0.080 +/- 0.004 m/s per vol%CO2; contralateral, 0.079 +/- 0.005 m/s per vol%CO2) at both hemispheres. In 16.5% of the patients, CRi reactivity was supranormal at the affected hemisphere. This phenomenon was due to an exaggerated dilatory response of the ipsilateral hemisphere and was combined with an absent CRi reactivity of the contralateral hemisphere (ipsilateral, 6.63 +/- 1.03 %CRi/vol%CO2; contralateral, -1.16 +/- 1.78 %CRi/vol%CO2). In contrast, hemispheric vmean reactivities were comparable (ipsilateral, 0.078 +/- 0.008 m/s per vol%CO2; contralateral, 0.077 +/- 0.008 m/s per vol%CO2). The remaining 18.7% showed severely diminished ipsilateral CRi reactivity (ipsilateral, 1.91 +/- 0.83 %CRi/vol%CO2; contralateral, 8.48 +/- 1.00 %CRi/vol%CO2) and vmean reactivity (ipsilateral, 0.073 +/- 0.007 m/s per vol%CO2; contralateral, 0.108 +/- 0.012 m/s per vol%CO2; P < .01), compatible with a significantly reduced perfusion pressure at the poststenotic hemisphere. CONCLUSIONS: Most asymptomatic patients do not suffer from severely abnormal hemodynamics at the poststenotic hemisphere. One small subgroup of patients presented with severely disturbed ipsilateral hemodynamics; another small subgroup demonstrated a steal phenomenon with secondary dilation of large cerebral vessels at the contralateral hemisphere. These subgroups require specific evaluation of proper treatment. PMID- 8202981 TI - Extent of pontine pyramidal tract Wallerian degeneration and outcome after supratentorial hemorrhagic stroke. AB - BACKGROUND AND PURPOSE: Pyramidal tract Wallerian degeneration has been detected on magnetic resonance imaging (MRI) as T2-weighted high-intensity areas. We analyzed the relation between the extent of brain stem Wallerian degeneration and activities of daily living (ADL) after supratentorial hemorrhagic stroke. METHODS: Twenty-six patients with supratentorial hemorrhage were examined on the coronal T2-weighted image of the pons 3 months or later after stroke, and the percentage of Wallerian degeneration in the pons was calculated. The patients were divided into three groups. In group A (n = 6), MR films were taken 3 to 6 months from the onset, and the ADL assessment was done within 2 months from the MRI. In group B (n = 11), MR films were taken 3 to 6 months from the onset, and the ADL assessment was done within 10 months from the MRI (mean, 15.5 months from the onset). In group C (n = 9), MR films were taken after 10 to 17 months (mean, 12.0 months) from the ictus, and the ADL assessment was done simultaneously. Barthel Index score was used for quantitative ADL assessment. RESULTS: All patients showed various degrees of pontine pyramidal tract Wallerian degeneration associated with capsular involvement by the hematoma. In group A, the percentage of degeneration did not correlate with the Barthel Index score (r = .2101, P = .6895). An inverse relation between percentage of degeneration and Barthel Index score was seen in groups B (r = .7354, P = .0099) and C (r = .888, P = .0014). In groups B and C, Wallerian degeneration was higher in patients with Barthel scores less than 60 (P = .005). CONCLUSIONS: The extent of pontine Wallerian degeneration on MRI 3 months or later after the stroke correlated with the patient's Barthel Index score 1 year after the stroke. PMID- 8202982 TI - Coagulation activity and emboli counts in patients with prosthetic cardiac valves. AB - BACKGROUND AND PURPOSE: The underlying embolic material detected by transcranial Doppler ultrasound in patients with prosthetic heart valves remains unknown. We undertook this study to evaluate the relation between the number of Doppler emboli signals and the activity of the coagulation system. METHODS: Patients with various types of prosthetic valves (n = 120) and patients in atrial fibrillation (n = 20) were monitored for 30 minutes using transcranial Doppler with a 2-MHz probe. The plasma concentrations of cross-linked D-dimer, antithrombin-III, and thrombin-antithrombin III complex were measured. RESULTS: No correlation between the levels of any of the hematologic parameters and the number of emboli was demonstrated in the studied groups. The D-dimer levels were significantly higher in patients with mechanical prosthetic valves with an international normalized ratio under 2.0 compared with those with an international normalized ratio between 2 and 3.5 or above 3.5, and in patients with Medtronic-Hall versus Bjork Shiley or Carpentier-Edwards valve prostheses. CONCLUSIONS: The lack of correlation between the activity of the coagulation system and the number of Doppler emboli in patients with prosthetic valves suggests that the underlying embolic material in these patients is not thrombotic. Our results also suggest that an increase of the anticoagulation intensity to an international normalized ratio above 3.5 does not result in a further decrease of the activity of the unstimulated coagulation system in patients with mechanical prosthetic valves. PMID- 8202983 TI - Should cerebral ischemic events in cancer patients be considered a manifestation of hypercoagulability? AB - BACKGROUND AND PURPOSE: Previous studies, mainly autopsy-based, suggest that the spectrum of stroke in cancer patients differs from that of the general population. These studies also suggest that cerebrovascular events frequently are a manifestation of hypercoagulability. However, no studies that address this question in the adult oncological population from a clinical perspective are available. We therefore assessed the clinical impact of cerebral ischemic events in cancer patients and attempted to determine whether their occurrence represents a manifestation of Trousseau's syndrome. METHODS: A computerized database that records all neurological admissions and consultations at a tertiary medical center was used to retrospectively identify all patients with cerebral ischemic events and cancer. RESULTS: Thirty-three patients representing 3.5% of all stroke consultations and admissions seen at the University of Massachusetts Medical Center were identified during the period 1988 through 1992. Large-vessel atherosclerosis was the most frequent cause of stroke. Furthermore, although 30% were determined to have hypercoagulability as a cause using clinical criteria, in only one of nine patients in whom tests were done was sufficient evidence present to make a presumptive diagnosis of disseminated intravascular coagulation. Irrespective of therapy, recurrent cerebral ischemic events were noted in only 6% of patients during a follow-up period averaging greater than 9 months, a figure that is similar to that for the risk of repeated events in the noncancer population. CONCLUSIONS: Recognizing the limitations of this retrospective study, it appears nonetheless that conventional stroke origins account for the majority of cerebral ischemic events in the adult cancer population. Although hypercoagulability is present to a greater extent than in the nononcological population, recurrent strokes seem to occur no more frequently than in the nononcological population, and antiplatelet agents seem sufficient therapy for most patients. PMID- 8202984 TI - Cerebral blood flow in migraine accompaniments and vertebrobasilar ischemia. AB - BACKGROUND AND PURPOSE: Transient neurological symptoms of brain stem or occipital lobe origin may be caused by transient ischemic attack in the vertebrobasilar territory (VB-TIA) or late-onset (or late-life) migraine accompaniment (LOMA). It is often clinically difficult to distinguish between VB TIA and LOMA. METHODS: Cerebral blood flow of 23 patients with VB-TIA, 24 with LOMA, and 28 age-matched control subjects was measured using the 133Xe inhalation regional cerebral blood flow (rCBF) technique. RESULTS: After adjusting for differences in baseline variables such as blood pressure, hematocrit, and PCO2, patients with VB-TIA had (1) lower mean rCBF than control subjects (P < .003) as measured by the initial slope index method; (2) more frequent anterior rCBF asymmetries than control subjects and patients with LOMA (P < .03 for both comparisons); and (3) higher mean interhemispheric rCBF differences compared with patients with LOMA (P = .08) and control subjects (P < .02). CONCLUSIONS: Regional CBF patterns in patients with VB-TIA and LOMA differ, with lower rCBF and more asymmetry of the anterior blood flows in patients with VB-TIA, probably reflecting the effects of stroke risk factors on the cerebral circulation. Patients with LOMA have rCBF patterns more closely resembling those of age matched healthy subjects. rCBF measurements may assist in the clinical diagnosis of VB-TIA and late-onset migrainous events. PMID- 8202985 TI - Chimeric 7E3 prevents carotid artery thrombosis in cynomolgus monkeys. AB - BACKGROUND AND PURPOSE: We compared the current antithrombotic strategy of antiplatelet therapy with aspirin, and anticoagulant therapy with heparin, with a specific genetically engineered chimeric antibody (c7E3 Fab) directed against the human glycoprotein IIb/IIIa receptor in an animal model of arterial thrombosis. METHODS: Anesthetized cynomolgus monkeys (Macaca fascicularis) were instrumented for monitoring of arterial blood pressure, heart rate, and carotid artery flow velocity. Animals were treated with saline (n = 6), aspirin (25 mg PO daily for 3 days; n = 6), heparin (100 U/kg i.v. plus infusion adjusted to maintain activated partial thromboplastin time at 2 to 3 times baseline; n = 6), aspirin plus heparin (as administered separately, n = 6), or c7E3 Fab (0.10 mg/kg i.v., n = 7; 0.15 mg/kg i.v., n = 6; 0.20 mg/kg i.v., n = 6; 0.25 mg/kg i.v., n = 6). Thrombus formation via anodal electrolytic stimulation (100 microA) to the intimal surface of the right carotid artery was initiated 15 minutes after drug administration and continued for 180 minutes. Electrolytic injury to the left carotid artery began 210 minutes after drug administration and continued for 180 minutes. Whole blood cell counts, glycoprotein IIb/IIIa receptor blockade, ex vivo platelet aggregation, template bleeding time, and activated partial thromboplastin time were assessed at various time points throughout the experimental protocol. RESULTS: Hemodynamic and hematologic parameters were comparable among groups at baseline. Treatment with c7E3 Fab inhibited ex vivo platelet aggregation, increased bleeding time, decreased thrombus weight, and increased time to occlusion in a dose-dependent manner in both vessels. Treatment with aspirin, heparin, or the combination of aspirin plus heparin was ineffective for the prevention of carotid artery thrombosis in this model. CONCLUSIONS: Inhibition of the platelet glycoprotein IIb/IIIa receptor with c7E3 Fab was found to be safe and effective for the prevention of primary thrombus formation, whereas treatment with either aspirin or heparin or the combination of the two agents failed to protect against occlusive thrombus formation in cynomolgus monkeys. PMID- 8202986 TI - Pretreatment of transient focal cerebral ischemia in rats with the calcium antagonist AT877. AB - BACKGROUND AND PURPOSE: The efficacy of pretreatment with the recently developed intracellular calcium antagonist AT877 against transient focal cerebral ischemia was investigated in rats subjected to middle cerebral artery occlusion and reperfusion using the endovascular suture method. METHODS: Halothane-induced moderate hypotension (60 mm Hg) was used during 100 minutes of temporary middle cerebral artery occlusion. In the treated animals (n = 10), an intravenous infusion of AT877 (0.03 mg/kg per minute) was initiated 30 minutes before the ischemic event and continued during the ischemic period. The control rats (n = 10) received physiological saline in a similar fashion. Local cerebral blood flow was measured by the hydrogen clearance technique. Neurological examinations were performed daily during the 48-hour observation period, and infarct size was assessed by triphenyltetrazolium chloride staining. RESULTS: A continuous infusion of AT877 significantly improved local cerebral blood flow during ischemia. The treated animals showed a better neurological outcome after a 24 hour observation period, and a significant reduction in ischemic brain injury resulted in both the neocortex (149 +/- 20 versus 41 +/- 14 mm3, P < .01) and the striatum (80 +/- 5 versus 46 +/- 8 mm3, P < .05). The size of the neocortical infarct was reduced, with increasing mean ischemic cerebral blood flow in the control and treated animals (r = .923, P = .0001). CONCLUSIONS: AT877 pretreatment was effective in preventing brain injury during transient focal cerebral ischemia and improving neurological status. This beneficial effect seems to be mediated, in part, by its primary action of increasing cerebral blood flow. PMID- 8202987 TI - The competitive NMDA antagonist MDL-100,453 reduces infarct size after experimental stroke. AB - BACKGROUND AND PURPOSE: The competitive N-methyl-D-aspartate antagonist MDL 100,453 was used to determine whether a neuroprotective effect is demonstrable when the drug is administered beginning 30 minutes after the initiation of focal ischemia and whether the effect is related to blood levels of the drug. METHODS: Forty-eight Sprague-Dawley rats were randomly assigned to one of four intravenous treatment categories: a bolus of 100 mg/kg MDL-100,453 followed by a saline infusion for 24 hours, isotonic saline as a bolus and 100 mg/kg per 24 hours of MDL-100,453 as an infusion over 24 hours, active drug in the bolus and 24-hour infusion, and control treatment of an isotonic saline bolus and infusion. Focal cerebral ischemia was induced by the intraluminal suture, middle cerebral artery occlusion method. The drug infusion was accomplished by an osmotic minipump implanted under the skin and attached to the jugular vein, which delivered drug or vehicle over a period of 24 hours. Infarct volume was calculated using 2,3,5 triphenyltetrazolium chloride staining after 24 hours of middle cerebral artery occlusion. RESULTS: Infarct volume of animals that received the MDL-100,453 bolus injection followed by MDL-100,453 infusion was significantly smaller than that of controls (P < .01). A significant effect of infusion on the reduction of extent of infarct size was also demonstrated (P = .015). Moreover, a statistically significant inverse correlation was demonstrated between the infarct volume and blood levels of MDL-100,453 at 60 minutes and 120 minutes after injection (r = .33 and r = -.49, respectively). CONCLUSIONS: We demonstrated a significant neuroprotective effect of MDL-100,453 when treatment was initiated 30 minutes after ischemia began and was maintained for 24 hours. PMID- 8202988 TI - Brain ischemia decreases phosphatidylcholine-phospholipase D but not phosphatidylinositol-phospholipase C in rats. AB - BACKGROUND AND PURPOSE: Phosphatidylcholine (PC)-phospholipase D (PLD) is an important intracellular signaling pathway in response to a variety of agonists, but little is known about the effects of brain ischemia on the PC-PLD system. We thus have examined the effects of global cerebral ischemia on PLD in rats. METHODS: We have examined the effects of global ischemia (decapitation or four vessel occlusion) on PLD and PLC activity in the membrane fraction of rat brains. We measured the PLD and PLC activity in detergent-mixed micelle assay systems using 3H-labeled exogenous substrate. RESULTS: The results demonstrate that basal PLD activity showed a gradual decrease with increased duration (5 to 30 minutes) of ischemia by decapitation in the hippocampus; after 30 minutes of ischemia, PLD activity was significantly decreased compared with the control. Lineweaver-Burk plots showed that the apparent Vmax value of PLD in ischemia was one half of that in the control without changes in Km value. Ischemia by decapitation significantly decreased PLD activity in the brain stem as well as the hippocampus, whereas in four-vessel occlusion study, ischemia significantly decreased PLD activity in the hippocampus but not in the brain stem. Lowered temperature (30 degrees C and 22 degrees C) during ischemic incubation did not reverse the ischemia-induced PLD activity decrease. In contrast to PLD, ischemia by decapitation had no effect on basal phosphatidylinositol-phospholipase C activity or the amount of phospholipase C beta 1 in the membrane fractions from 30-minute ischemic hippocampus by immunoblots probed with the antibody. CONCLUSIONS: These results suggest that PC-PLD is one of the target enzymes of ischemia; its decrease may cause a perturbation of PC hydrolysis and/or disorders of intracellular transduction of signals or choline metabolism for acetylcholine formation in brain. PMID- 8202989 TI - Magnetic resonance imaging assessment of evolving focal cerebral ischemia. Comparison with histopathology in rats. AB - BACKGROUND AND PURPOSE: This study was performed to document the progression of ischemic brain damage after middle cerebral artery occlusion in the rat using magnetic resonance imaging and histopathologic methods. METHODS: Cerebral ischemia was induced through permanent tandem occlusion of ipsilateral middle cerebral and common carotid arteries. The evolution of magnetic resonance imaging and histopathologic parameter changes was studied, both short term (1.5 to 8 hours) and long term (24 to 168 hours), in five specific brain regions within the middle cerebral artery territory. RESULTS: Significant changes in proton nuclear magnetic resonance spin-lattice and spin-spin relaxation times and the "apparent" diffusion coefficient of water could be detected within hours after the onset of permanent focal cerebral ischemia, whereas significant alterations in proton spin density ratios were not apparent until approximately 48 hours. Histological changes were evident within 12 hours, with a significant loss of neurons seen in the most severely damaged regions at 7 days. Diffusion-weighted imaging was the most sensitive technique for visualizing acute ischemic alterations. The water diffusion coefficient was the only magnetic resonance imaging parameter studied to indicate significant alterations within the first 4 hours after arterial occlusion in all five brain regions. CONCLUSIONS: The degree of change for a particular magnetic resonance imaging parameter appeared to be related to the location and extent of neuronal injury, with the most dramatic changes occurring within the areas displaying the most severe histological damage. These results indicate that complete specification of all brain regions affected by ischemic brain injury may require a combination of imaging strategies applied over a period of days and suggest the possibility of using magnetic resonance imaging to distinguish between permanent and reversible cell damage. PMID- 8202990 TI - Interrater agreement in evaluation of stroke patients with the unified neurological stroke scale. AB - BACKGROUND: We sought to determine interrater agreement in evaluation of stroke patients with the Unified Form for Neurological Stroke Scales (UFNSS). SUMMARY OF REPORT: Fifty inpatients were independently examined by three neurologists. Kendall coefficients of concordance were computed for the different items of the UFNSS. There was a high concordance among the raters. The best agreements were obtained for motor functions and the worst for grading of eye movements. CONCLUSIONS: The UFNSS was shown to be reliable for evaluation of motor functions, verbal communication, orientation, and vigilance in stroke patients. PMID- 8202991 TI - A pediatric case of carotid rete mirabile. AB - BACKGROUND: Carotid rete mirabile (CRM) is a physiological network between the external carotid and internal carotid systems in lower mammals. Very rarely, these arterial channels are observed in humans. CASE DESCRIPTION: We describe a 13-year-old girl with CRM who presented with acute hemiplegia after an operation for Dieulafoy's ulcer, a submucosal vascular anomaly of the stomach. Angiogram revealed hypoplasia of the bilateral internal carotid arteries. The abnormal network from the external carotid system was seen around the cavernous portion of the internal carotid arteries. The ophthalmic arteries were developed as the collateral pathway. CONCLUSIONS: To our knowledge, this is the first pediatric case reported in the literature. CRM sometimes accompanies intracranial or systemic vascular disorders such as cerebral aneurysm and pseudoxanthoma elasticum. CRM is a unique pathological condition that presents as a hemorrhagic or ischemic cerebrovascular disorder. PMID- 8202992 TI - Central retinal artery occlusion from carotid dissection diagnosed by cervical computed tomography. AB - BACKGROUND: Carotid dissection may lead to many different types of neurological deficits, both transient and permanent. CASE DESCRIPTION: We present a patient with an isolated central retinal artery occlusion who was found to have an ipsilateral carotid dissection by neck computed tomographic scan, later confirmed by angiography. CONCLUSIONS: This is the first reported case of carotid dissection causing central retinal artery occlusion without any other neurological deficits. It demonstrates the diagnostic usefulness of computed tomographic imaging in such cases. PMID- 8202993 TI - Vertebrobasilar junction fenestration associated with dissecting aneurysm of intracranial vertebral artery. AB - BACKGROUND: Vertebrobasilar junction fenestration is considered to be a subtype of fenestration of the proximal basilar artery, which has been described only in autopsy cases. The fenestration associated with a dissecting vertebral aneurysm is extremely rare. CASE DESCRIPTION: A 47-year-old man presented with subarachnoid hemorrhage. The four-vessel angiogram showed a fusiform dilatation with an intimal flap of the left vertebral artery distal to the origin of the posterior inferior cerebellar artery and a fenestration at the vertebrobasilar junction, in which a small limb of the fenestration arising from the distal portion of the left vertebral artery bridged the proximal basilar trunk, while another limb had a large diameter showing the same diameter as the basilar artery. The dissecting aneurysm was treated with body clipping by directly clipping the ruptured portion of the aneurysm via a suboccipital approach in an early operation 48 hours after the ictus. The patient had a good recovery and returned to his work. He is well at a 5-year follow-up. CONCLUSIONS: The relevant angiographic features of the vertebrobasilar junction fenestration and the surgical treatment of such associated aneurysms are discussed. PMID- 8202994 TI - Internal carotid artery dissection after remote surgery. Iatrogenic complications of anesthesia. AB - BACKGROUND: Subintimal dissection with acute occlusion of the internal carotid artery resulting in acute cerebral infarction has not been reported as an iatrogenic complication of general anesthesia. CASE DESCRIPTIONS: An anesthetist stretched the neck of a 44-year-old man by anchoring an anesthesia mask posterior to the angle of the jaw with overlying fingers as the patient struggled during an insufficient inhalational mask anesthetic. A 33-year-old man received an endotracheal anesthetic without struggle, but as he was turned from a supine to a prone position, his head and neck were not immobilized to rotate with his torso during the move. The next day both patients suffered acute cerebral infarctions secondary to ICA dissections and occlusions (angiographically demonstrated). CONCLUSIONS: Stretching the soft neck tissues of anesthetized patients can cause internal carotid artery dissection and acute cerebral infarction. PMID- 8202995 TI - Bilateral infarction in the anterior cerebral artery vascular territory due to an unusual anomaly of the circle of Willis. AB - BACKGROUND: Bilateral infarction in the anterior cerebral artery vascular territory is rare and usually results from rupture of an aneurysm of the anterior communicating artery. In the case of an anomaly of the anterior part of the circle of Willis, thrombosis also may lead to bilateral infarction. CASE DESCRIPTION: A 73-year-old right-handed man presented with a complete loss of communicative behavior and an almost complete quadriplegia. 99mTc hexamethylpropyleneamine oxime single-photon emission-computed tomography (HMPAO SPECT) of the brain showed a "horseshoe" image, reflecting bilateral perfusion defects in areas supplied by the anterior cerebral arteries. Postmortem examination of the brain revealed an unusual anomaly of the circle of Willis in which the postcommunicating part of the right anterior cerebral artery was absent. CONCLUSIONS: In our patient a unique developmental anomaly of the circle of Willis indirectly contributed to bilateral infarction in the territory of the anterior cerebral artery. The patient's neuropsychological profile, dominated by akinetic mutism, was highly suggestive of involvement of the receptive language modalities. For the first time, 99mTc-HMPAO SPECT of the brain revealed a horseshoe image in bilateral infarction in the territory of the anterior cerebral artery. PMID- 8202996 TI - Pharmacotherapy of aphasia. A critical review. AB - BACKGROUND: Communication problems are a common sequela of cerebrovascular disease and other central nervous system disorders. Behavioral treatment of these disorders aims to harness uninjured parts of the brain to improve the communicative life of the individual. While pharmacotherapy has held promise for the treatment of aphasia for over 50 years, it has not fulfilled this promise. This article reviews both the promise and the disappointment of aphasia pharmacotherapy. SUMMARY OF REVIEW: Diverse theories of the underlying neurological deficits in aphasia have led to different pharmacologic rationales for therapy. Animal studies have demonstrated decreased levels of brain catecholamines after cortical stroke and more rapid stroke recovery with therapy aimed at augmenting brain norepinephrine and dopamine. These studies have led to recent attempts to hasten or extend language and sensorimotor rehabilitation after human stroke by administration of catecholaminergic drugs. When used as an adjunct to behavioral therapy, such pharmacotherapy appears to have benefit. CONCLUSIONS: While drug therapy is unlikely to revolutionize the treatment of aphasia, it nonetheless holds promise as an adjunct to behavioral speech and language therapy to decrease performance variability and consequently to improve mean performance in patients with mild to moderate language dysfunction. Additional studies with carefully designed methods are necessary to assess the full potential of aphasia pharmacotherapy. PMID- 8202997 TI - Stroke: the way things really are. AB - BACKGROUND: To comply with governmental requirements regarding the validity of therapeutic modalities and for medico-legal purposes, it is important to distinguish between what has been scientifically proven and what is anecdotal in the prevention and management of stroke. SUMMARY OF REVIEW: This review summarizes the evidence for many of the modalities used to prevent stroke in high risk patients, including antiplatelet drugs, anticoagulants, and endarterectomy, and the limitations of each. Controversial therapeutic modalities for which no scientific proof exists, such as anticoagulation of progressing stroke, are also discussed. The term "standard of care" should apply to modalities proven to be effective by scientifically controlled studies, not because they are used by many physicians. Treatment of acute stroke is still disappointing despite the development of many promising pharmacological strategies in experimental animals. An important part of the reason may be that the window of therapeutic opportunity is much shorter than the usual entry time of patients in most clinical trials. This logistic problem merits serious attention. CONCLUSIONS: Numerous controlled, randomized, multiple-center clinical trials have demonstrated that the efficacy or lack thereof of various therapies directed at preventing or treating stroke can be determined and that anecdotal data may be misleading and harmful. At the least we should be aware of what we know and what we do not. PMID- 8202998 TI - Predicting length of stay in the rehabilitation of stroke patients. PMID- 8202999 TI - Left atrial spontaneous echo contrast and embolism. PMID- 8203000 TI - Flow and velocity during autoregulation testing in humans. PMID- 8203001 TI - Silent brain infarct in thrombotic thrombocytopenic purpura. PMID- 8203002 TI - Segmental narrowing of the supraclinoid carotid artery in young patients with ischemic stroke. PMID- 8203003 TI - Guidelines for the management of transient ischemic attacks. From the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks of the Stroke Council of the American Heart Association. PMID- 8203004 TI - Narcissistic crises of aging and suicidal despair. PMID- 8203005 TI - The heavy metal subculture and suicide. AB - The impact of the heavy metal music subculture on suicide has been the subject of much public debate but little scholarly research. The present paper assesses this relationship with data on heavy metal magazine subscriptions and youth suicide in the 50 states. We find that, controlling for other predictors of suicide, the greater the strength of the metal subculture, the higher the youth suicide rate. The music perhaps nurtures suicidal tendencies already present in the subculture. The model explains 51% of the variance in youth suicide. PMID- 8203006 TI - California's suicide decline, 1970-1990. AB - From 1970 to 1990 California experienced a 32% decline in suicide, which was particularly pronounced among women, non-whites, the young, and urban dwellers. Suicide declines of over 50% were recorded in San Francisco and Los Angeles, and large decreases occurred in other coastal counties. Additionally, California was the only one of 51 states to show a consistent decline in teenage and young-adult suicide (accompanied by an 88% decrease in teenage drug and other poisoning deaths). Initial investigation of death certification, accident and homicide trends, economic measures, and prevention efforts did not produce an explanation for a suicide decrease of California's magnitude. However, the state does display anomalous trends in certain social measures (reduced divorce, rising non-White population, and rising homicide) that point to multifactorial hypotheses including demographic changes and changed attitudes toward violence. Review of the accuracy of past suicide certification procedures nationally is also indicated. PMID- 8203007 TI - Suicide ideation and creative problem solving. AB - This investigation utilized the recent technology for the assessment of creativity to examine the association between problem solving and suicide ideation. Three kinds of problem-finding and -solving tasks were administered to 81 (nonclinical) college students. One of these tasks assesses "problem generation" and was expected to be particularly informative, given that individuals considering suicide may perceive many problems but find few solutions. Results supported this expectation: Problem generation scores were significantly correlated with suicide ideation, even after stress was statistically controlled. A secondary analysis suggested that the originality and flexibility of solutions may be influenced by the particular problem an individual faces. PMID- 8203008 TI - Stress, coping, and suicide risk in psychiatric inpatients. AB - The present study investigated the relationship between interpersonal problems, coping styles, and suicide risk. Seventy-one adult psychiatric inpatients completed a suicide risk scale, a measure of interpersonal problems, and a coping scale designed to measure eight coping styles. Patients admitted with a history of suicidal attempts were compared with patients admitted for other reasons. Interpersonal problems were found to be significantly and positively related to suicide risk. The coping style of "suppression" (tendency to avoid threatening or uncomfortable situations) was found to be significantly and positively related to suicide risk [F(2, 68) = 4.54, p < .01]. Several other coping styles were found to be significantly related to suicide risk. These findings are congruent with a "two-stage model of countervailing forces" and have both research and clinical implications. PMID- 8203009 TI - The comorbidity of post-traumatic stress disorder and suicidality in Vietnam veterans. AB - Vietnam veterans (N = 232) recruited from three sources were assessed for suicidal thinking and behaviors, and symptoms of posttraumatic stress disorder (PTSD) and depression. Findings support the notion that suicidal thoughts are prevalent in this group, with veterans in psychotherapy reporting a greater likelihood of such symptoms (82.6%) than veterans in the community (35.7%) or those seeking assistance through a veteran's outreach center (66.7%). Thoughts of ending one's life and a previous suicide attempt were significantly correlated with a diagnosis of PTSD (r = .53, p < .001; and r = .33, p < .001, respectively). Veterans with a diagnosis of PTSD and depression or dysthymia were also more likely to report suicidal thinking and behaviors than veterans with only one of the diagnoses. PMID- 8203011 TI - A comparison of 15 theories of suicide. AB - A method is illustrated for studying the lives of suicidal individuals. Each of 15 theories of suicide is operationalized with 10 statements. These 150 statements are then rated as present or absent in the lives of 30 famous suicides for whom a biography is available. The theory of Aaron Beck is found to be most applicable to the suicidal lives and that of Sigmund Freud least applicable. A factor analysis has identified five clusters of theories; and the age, sex, national origin, era, and experience of loss are found to be associated with scores of the 30 suicides on the 15 theories. PMID- 8203010 TI - Dissociation, physical pain, and suicide: a hypothesis. AB - The hypothesis of this paper states that at least some suicidal individuals are characterized by a disposition toward dissociation manifested in relative insensitivity to physical pain and indifference to their bodies. Three main topics are discussed: dissociation and suicide, psychological aspects of pain, and pain and suicide. Various theoretical and experimental studies suggest that certain stress conditions lead to the development of dissociative tendencies, and that once these tendencies are established, they become an integral part of suicidal behavior. Psychological variables that affect pain tolerance are presented and they include perception, motivation, emotions, and behavioral and cognitive strategies of pain control. These can increase tolerance of pain in suicidal individuals, making the suicidal act possible. The specific relationships of pain and suicide are then introduced through an examination of pain analgesia in the phenomenon of self-harm. The integration of the material suggests that early and continuous stress lead to the simultaneous development of dissociative tendencies (including indifference to the body and pain) and heightened vulnerability to stress. These dispositions may facilitate suicidal behavior in the face of mounting intolerable stress, helplessness, and hopelessness. Preliminary empirical support for the present hypothesis is cited. This hypothesis shifts the focus of attention from the question of what causes suicide to what facilitates suicide, and in so doing suggests new directions for research and therapy. PMID- 8203012 TI - Community suicide prevention: the effectiveness of bridge barriers. PMID- 8203013 TI - Enzymes as RNA-binding proteins: a role for (di)nucleotide-binding domains? PMID- 8203014 TI - Regulating the regulators. PMID- 8203015 TI - Cytosine nucleoside/nucleotide deaminases and apolipoprotein B mRNA editing. PMID- 8203016 TI - A conserved domain in putative bacterial and bacteriophage transglycosylases. PMID- 8203017 TI - DRTF1/E2F: an expanding family of heterodimeric transcription factors implicated in cell-cycle control. AB - During the cell cycle, the transcription of certain genes is integrated with cell cycle progression, thus providing an important level of control. In mammalian cells, DRTF1/E2F is a transcription activity comprising a group of related heterodimeric transcription factors that function in this integration process. The primary molecules involved in generating the afferent signals that converge on DRTF1/E2F belong to a class of proteins, exemplified by the retinoblastoma tumour suppressor gene product, whose activities are, in turn, regulated by cyclin-dependent kinases. The transcriptional activity of DRTF1/E2F is therefore regulated through a pathway that links the machinery of the cell cycle to the transcription apparatus. As such, it is likely to play a pivotal role in regulating cell-cycle progression. PMID- 8203018 TI - Multidrug resistance pumps in bacteria: variations on a theme. AB - Multidrug resistance pumps (MDRs) arise from three different gene families and are widespread in bacteria. For example, in Escherichia coli alone, there seem to be seven distinct MDRs. The most common belong to the major facilitator family of membrane translocases; this type of MDR is closely related to specific antibiotic extrusion pumps such as the tetracycline/H+ antiporter. This similarity in design, and the high incidence of apparently independent evolution of MDRs, suggests that the property of multidrug resistance might have resulted from a loss of specificity in a specific hydrophobic-drug efflux pump. PMID- 8203019 TI - Calnexin: a membrane-bound chaperone of the endoplasmic reticulum. AB - Calnexin is a new type of molecular chaperone that interacts with many nascent membrane and soluble proteins of the secretory pathway. Calnexin is unrelated to molecular chaperones of the Hsp60, Hsp70 and Hsp90 families, and is further distinguished from them in that it is an integral membrane protein. One of its demonstrated functions is the retention of incorrectly or incompletely folded proteins, suggesting that calnexin is a component of the quality control system of the endoplasmic reticulum. PMID- 8203020 TI - The three-dimensional structure of a molecular motor. AB - Myosin is one of only three proteins known to convert chemical energy into mechanical work. Although the chemical, kinetic and physiological characteristics of this protein have been studied extensively, it has been difficult to define its molecular basis of movement. With the recent X-ray structural determination of the myosin head, however, it is now possible to put forward a hypothesis on how myosin might function as a molecular motor. PMID- 8203021 TI - Kinemages--simple macromolecular graphics for interactive teaching and publication. PMID- 8203022 TI - Methods and reagents. Ghost plasmid of pBluescript. PMID- 8203023 TI - Viral, worm and radical implications for apoptosis. PMID- 8203024 TI - [Treatment of intermittent divergent strabismus]. PMID- 8203025 TI - [Epidemiological study of otospongiosis in the Nabeul region]. PMID- 8203026 TI - [Etiology of acute diarrhea in children]. PMID- 8203027 TI - [Sampling protocol in an epidemiological population survey]. PMID- 8203028 TI - [Value of morphological and infra-red analysis of calculi in the etiologic diagnosis of urinary lithiasis]. PMID- 8203029 TI - [Cystic gastritis: 8 case reports]. PMID- 8203030 TI - [Clinical aspects of Schwartz Jampel syndrome: 4 new familial case reports and review of the literature]. PMID- 8203031 TI - [Methyldopa-induced hepatitis: 3 case reports]. PMID- 8203033 TI - [The skeleton: a real bazaar! (Part II)]. PMID- 8203032 TI - [Paraesophageal cyst (a case report)]. PMID- 8203034 TI - [1. Primary prevention of abusive treatment inflicted on children (part I)]. PMID- 8203035 TI - [Update on menopause]. PMID- 8203036 TI - [Hirsutism in an obese patient]. PMID- 8203037 TI - [What should be the role of antilipemic agents in the control of hypercholesterolemia in elderly persons?]. PMID- 8203038 TI - [Marcel Proust: asthma, a redoutable master, a loyal servant...]. PMID- 8203039 TI - [Polycystic kidney]. PMID- 8203040 TI - [The question of diabetes]. PMID- 8203041 TI - [Abdominal pain in a young women]. PMID- 8203042 TI - [Familial adenomatous polyposis]. PMID- 8203043 TI - [What use is made of acyclovir in immunocompetent patients?]. PMID- 8203044 TI - [The use of diagnostic and surgical procedures in elderly persons in Quebec]. AB - The rapid aging of the population constitutes a new challenge for the health care delivery system. This paper presents the progression of use of several diagnostic and surgical procedures in the elderly in Quebec from 1981 to 1989. Data were obtained from claims to the Regie de l'assurance maladie du Quebec for the years 1981, 1985 and 1989. The rate of coronary artery bypass surgery increased by more than 700% in people 65 years and over between 1981 and 1989. This increase was especially high in the oldest age group (q 75 years). There was also a significant increase in surgery for abdominal aortic aneurysm, while the rate of carotid endarterectomy remained stable for people 65 years and over during this period. The rates of all abdominal surgical procedures examined (appendicectomy, repair of hiatal and inguinal hernia, cholecystectomy and colectomy) were relatively stable in elderly during the study period. Total hip replacement more than doubled in people 65 years and over, while other types of hip arthroplasty significantly decreased over this period. All types of diagnostic procedures examined (coronary angiography, bronchoscopy, gastroduodenoscopy and retrograd cholangio-pancreatography) increased significantly, especially in very old people. This study suggests that surgical care is increasing in the elderly in Quebec. This progression is expected to continue in the coming years so that surgical care of the elderly will become a significant part of our health care delivery system. PMID- 8203045 TI - [When one does not have the blues, then one has some spirit]. PMID- 8203046 TI - [The indelible traces of a destructive genius (Adolf Hitler)]. PMID- 8203047 TI - [The epidemiology of hepatitis B in Quebec]. PMID- 8203048 TI - [The lowering of serum cholesterol in the prevention of coronary disease (part 1). The Canadian Study Group for Periodic Medical Examinations]. PMID- 8203049 TI - Urinary acidification and urinary excretion of calcium and citrate in women with bilateral medullary sponge kidney. AB - Urinary acidification ability, acid-base status and urinary excretion of calcium and citrate were evaluated in 10 women with bilateral medullary sponge kidney (MSK) and in 10 healthy women. Patients with MSK had higher fasting urine pH compared to normal controls (p < 0.01). Four patients had incomplete renal tubular acidiosis (iRTA), 3 had hypercalciuria, and 5 patients had hypocitraturia. The 24-hour urinary excretion of calcium was increased in the females with MSK (5.23 +/- 0.78 mmol) compared to the healthy females (3.49 +/- 0.29 mmol) (p < 0.02), and increased in MSK patients with iRTA (7.32 +/- 1.45 mmol) compared to patients with normal urinary acidification (3.83 +/- 0.12 mmol) (p < 0.01). The patients with iRTA had reduced levels of plasma standard bicarbonate (20.5 +/- 1.0) after fasting compared to patients with normal urinary acidification (23.8 +/- 0.8) and healthy women (22.7 +/- 0.6) (p < 0.01), and reduced levels of 24-hour urinary excretion of citrate (0.93 +/- 0.25 mmol) compared to patients with normal urinary acidification (3.58 +/- 0.51) and healthy women (2.78 +/- 0.49) (p < 0.005). A positive correlation was found between the degree of acidosis during ammonium chloride loading and urinary excretion of calcium (r = 0.71, p = 0.02), and a negative correlation between the degree of acidosis during ammonium chloride loading and urinary citrate excretion (r = 0.87, p = 0.001). The results suggest that defective urinary acidification might play an important role in the mechanism of hypercalciuria and hypocitraturia in patients with medullary sponge kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203050 TI - Are auxiliary methods necessary prior to ESWL in patients with a solitary kidney? AB - Between January 1985 and October 1991, 54 patients with calculi in a solitary kidney were treated by ESWL using the Dornier HM-3 lithotriptor. The mean age of the patients was 53.9 years (range 24-77 years). In 51.9% of the cases the stones measured > 1 cm in diameter, in 42.6% between 0.4 and 1 cm, and in 5.5% < 0.4 cm in diameter. In 39 of the 54 patients (72.2%) the calculi could be disintegrated by a single ESWL treatment. In 12 patients (22.2%) 2 ESWL treatments were necessary, and another 3 patients (5.6%) needed 3 ESWL treatments. In 6 cases (11.1%) percutaneous nephrostomy (PCN) was needed, and in 8 other patients ureteric stents were inserted prior to ESWL because of obstruction of the upper urinary tract, causing impending urosepsis in 8 of these 14 cases. Following ESWL, PCN was performed in 4 cases (7.4%) and a ureteric stent was inserted in 2 patients (3.7%) because of urinary obstruction. At discharge from the hospital 15 of the 54 patients (27.8%) were stone-free and 34 patients (63.0%) had small residual fragments of < 0.4 cm in diameter. One year after treatment, 42 patients could be evaluated at a control examination. 37 of these 42 patients (88.1%) were stone-free and 3 patients (7.1%) showed residual fragments of < 0.4 cm. In conclusion, our results demonstrate that, if there is no ureteric obstruction present prior to ESWL, the majority of patients with a solitary kidney do not present extraordinary problems and do not need auxiliary procedures. PMID- 8203051 TI - Ureteropelvic junction obstruction: relation of etiology and age at surgical repair to clinical outcome. AB - Ureteropelvic junction (UPJ) obstruction is a congenital anomaly either caused by intrinsic narrowing of the upper ureter or by extrinsic pressure on the ureter caused by aberrant vessels or fibrous bands. We reviewed 121 cases of pyeloplasties performed in our department for UPJ obstruction. The cases were grouped by age and by the underlying pathology. Postoperative urographic evaluation showed that dismembered pyeloplasty was successful in 98.4% of the patients, with no significant difference between age groups. Persistence or recurrence of preoperative symptoms occurred in some patients (16.6%). Extrinsic obstruction of the ureter was associated with better postoperative clinical results and less recurrence of symptoms. PMID- 8203052 TI - Immunocytochemically demonstrated expression of epithelial membrane antigen and carcinoembryonic antigen by exfoliated urinary cells in patients with bladder cancer. AB - The localization of epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA) in exfoliated cells from voided urine was examined to clarify whether immunostaining for these markers is more useful than conventional cytology for diagnosis of patients with transitional cell carcinoma of the bladder. Both EMA and CEA were present more frequently in specimens from higher grade and higher-stage tumors than lower-grade and lower-stage tumors. Cells positive for one or both of these markers were also found in specimens from cancer patients with only suspicious results by conventional cytology. In grade 1 tumors, the positive rates were 50% for EMA staining and 40% for CEA staining compared with 10% for conventional cytology. In 12 patients with cystitis, results for EMA staining and conventional cytology were all negative, whereas CEA staining proved positive in 6 patients (50%). None of 10 normal subjects with conventional cytology had positive results for EMA or CEA staining. These findings indicate that immunocytochemistry for EMA is a more useful adjunctive method than CEA staining or conventional cytology for detection of tumor cells, especially in cases of low-grade bladder cancer. PMID- 8203053 TI - DNA aneuploidy in G1-urothelial carcinomas of the urinary bladder. AB - Thirty G1-urothelial carcinomas of the bladder were investigated using DNA cytophotometry. Specimens obtained by tumour resection and quadrantic biopsy were first fixed in formalin and then embedded in paraffin. The cells were then separated using the method developed by Hedley. The DNA content was established after Feulgen staining using a TV-based image analysis system. DNA aneuploidy, a marker for neoplasia, was investigated using the so-called stemline interpretation developed by Bocking. This method compares the DNA content of the G0/1 tumour cells in the cell population to be analysed with the reference cell population, using the Kolmogoroff-Smirnow test (p < 0.001). On this basis, 23 tumours (76.6%) were DNA aneuploid, whereas if DNA aneuploidy is defined (as conventionally) as a DNA content of > 2.2c, only 17 tumours (56.6%) were found to be DNA aneuploid. The mean stemline value was 2.4c (range 1.85-3.96). By using a more precise TV-based image analysis system and this new DNA stemline interpretation, the rate of detection of DNA aneuploidy was improved by 20%. The diagnosis of G1-urothelial carcinomas by DNA cytophotometry is at least 25% more sensitive than that using conventional cytology (20-50%). We suggest that modified DNA cytophotometry could be a useful, additional diagnostic tool in examining doubtful urinary samples. PMID- 8203054 TI - Complications in a personal series of one hundred and five radical cystectomies: specific problems in a developing country. AB - During the 6-year period 1986-1992, 105 patients with muscle invasive bladder cancer underwent radical cystectomy in our department. All the operations were done by the principal author using the same standard technique. Herein we analyse our perioperative complication rate and highlight some of the surgical steps which contribute to this low complication rate. PMID- 8203055 TI - A new theory of micturition and urinary continence based on histomorphological studies. 2. The musculus sphincter vesicae: continence or sexual function? AB - Results of a histomorphological study of serial sections carried out in frontal, transversal and sagittal directions in 65 bladder necks are presented. It is shown that the trigonal system of the urinary bladder consists of two anatomical structures: first, of a muscle originating from the muscle system of both ureters and converging to form within the bladder the interureteric ridge, the musculus interuretericus and of a second structure forming the actual trigonum vesicae. It is the musculus sphincter trigonalis or musculus sphincter vesicae. This muscle elliptically embraces the internal urethral orifice and is only formed by one muscle lamella. It does not as has often been described extend in any form to the urethra or to the surroundings. The so-called Bell muscle does not exist. During the reproductive years the lower part of the sphincter trigonalis is strongly pervaded with prostate tissue. This could enable the muscle to have a double function: a continence function in accordance with a consequent distinction between the urinary bladder and the urethra as urinary and sexual tract, and during ejaculation the muscle could prevent the retrograde ejaculation and on the other hand the contraction of the muscle could lead to the release of the prostate secretion. PMID- 8203056 TI - Incidence of antisperm antibodies in patients with carcinoma of the testis and in subfertile men with normogonadotropic oligoasthenoteratozoospermia. AB - The incidence and the clinical relevance of sperm-reactive antibodies in subfertile men and in testicular cancer patients were assessed in a pilot study. The sera of 42 men with normogonadotropic oligoasthenoteratozoospermia (OAT syndrome, n = 20) or carcinoma of the testis after inguinal semicastration (n = 22) were analyzed for agglutinating antisperm antibodies using fluorescein labeled antiglobulin. In the group with the OAT syndrome, the incidence of sperm reactive antibodies was only 5%, which is comparable to that in normal fertile men. Although the incidence of 18% in the testicular cancer patients was markedly higher, only 2 of the patients in question had abnormal spermiograms, which in one case could, moreover, be explained by previous radiation therapy. In summary in this small group of patients, serum monitoring for sperm-reactive antibodies appeared to be of limited clinical relevance in patients with the OAT syndrome and in testicular cancer patients. PMID- 8203057 TI - Klinefelter syndrome associated with 13/14 translocation abnormality 46,XXY,t(13q;14q). AB - In this communication, a case of Klinefelter syndrome associated with a 13/14 translocation is described. Such a rare occurrence is most probably due to the de novo arrangement of chromosomes related to the advanced ages of both parents at conception. PMID- 8203058 TI - Bilateral ovarian metastasis from left renal cell carcinoma. AB - We report a case of left renal cell carcinoma with bilateral ovarian metastasis which was demonstrated 3 years after radical nephrectomy. The patient is alive without any evidence of disease 36 months after bilateral salpingo-oophorectomy. PMID- 8203059 TI - Adenocarcinoma of the renal pelvis. A report of two cases. AB - Two cases of intestinal-type adenocarcinoma of the renal pelvis (ARP) in 48- and 63-year-old females are presented. Both had a previous history of urinary obstructive disease, one secondary to staghorn calculus and the other to postirradiation stenosis following treatment for carcinoma of the cervix. Immunohistochemical findings revealed marked positivity to epithelial membrane antigen and focal positivity to cytokeratins and carcinoembryonic antigen. Chronic irritation of the renal pelvis plays an important role in the pathogenesis of ARP. In one of our cases of multicentric origin, the synergistic effect of pelvic irradiation and cyclophosphamide chemotherapy in a patient with a previous squamous cell carcinoma of the cervix, may be responsible for the pathogenesis of the ARP. PMID- 8203060 TI - Emphysematous pyelonephritis, ureteritis, and cystitis in a diabetic patient. AB - This paper presents a case of gas-forming infection of the urinary tract in a diabetic patient. Plain film and computed tomography scans of the abdomen greatly facilitated clarification of the entire inflammatory process. The patient was cured by early nephrectomy conducted following unsuccessful treatment by percutaneous drainage. PMID- 8203061 TI - Spontaneous rupture of bladder in pregnancy. A case report. AB - A case of spontaneous rupture of bladder in pregnancy is reported. Due to its rarity, the diagnosis of this condition is difficult. PMID- 8203062 TI - [Extracorporeal lithotripsy in certain forms of urolithiasis]. AB - Therapeutic results of remote lithotripsy have been analyzed for 1016 patients with urolithiasis. The authors also focus on specific features of remote lithotripsy in anomalous stones, in nephroliths on the single and transplanted kidney, in location of the stone in the ureter. The efficacy of the procedure is reviewed in pediatric patients. Satisfactory results were achieved in 962 patients (95%). Remote lithotripsy is considered to be a valuable component of combined treatment of urolithiasis replacing successfully open surgery in 95% of the cases. PMID- 8203063 TI - [The effect of the physicochemical structural properties of urinary calculi on the results of extracorporeal shockwave lithotripsy]. AB - The relation of chemical composition and structure of uroliths to lithotripsy effects was evaluated with regard to the concrement size, location, time of the intraureteral persistence, etc. Besides, a prognosis of the remote impulse lithotripsy (RIL) outcome was attempted by x-ray picture and crystallization alterations in the urine. 54 patients with nephroliths and 73 patients with ureteroliths (overall 137 concrements) were examined. By RIL results, the patients were divided into 2 groups: those who benefited from RIL and those who failed it. Worse results were obtained in cases of oxalate concrements with radial-concentric structure and with phosphate ones composed primarily of hydroxylapathite. RIL efficacy was found to depend on a number of interrelated factors (chemical structure, location, size of the concrement, duration of its existence in the ureter). In long-standing ureteroliths the outcomes are associated with stone structure. The denser is the concrement the more probable is its strangulation and more apparent is periureteritis. Changes in crystallization can prompt RIL prognosis as well as it is possible by x-ray picture. PMID- 8203064 TI - [Nikolai Alekseevich Lopatkin (on his 70th birthday)]. PMID- 8203065 TI - [The therapy of chronic nonobstructive pyelonephritis]. AB - Combined therapy for chronic nonobstructive pyelonephritis introduced by the authors includes such components as etiological, pathogenetic, resistance stimulating. The cure was achieved in 60% of the patients. PMID- 8203066 TI - [The suppression of the Ca ATpase activity of rat kidney microsomes under the action of blood plasma as an index of the severity of the status of pyelonephritis patients]. AB - Whether blood plasma from 63 pyelonephritis patients can inhibit Ca-ATPase activity when compared to known toxicity marker (middle-sized molecule number) was studied. This was done to assess diagnostic potentialities of the test based on the ability of plasma from pyelonephritis patients to inhibit the test enzymatic system, i. e. Ca-ATPase activity of the microsome fraction from renal cortex in intact rats. The inhibition of Ca-ATPase activity by the plasma is shown to correlate with inflammation activity and the patients condition. In pyodestructive acute pyelonephritis this inhibition reached 60.6 +/- 3.86%, in acute serous pyelonephritis 36.02 +/- 1.54%. It follows, that the above parameter is more informative than the number of middle-sized molecules and can be introduced as one of the criteria of the patients' condition and for choice of treatment. PMID- 8203067 TI - [The characteristics of an acute infectious-inflammatory process in the single remaining kidney (experimental and clinical study)]. AB - The paper is concerned with acute pyelonephritis pathogenesis in patients with a solitary kidney. Upon nephrectomy, the remaining kidney undergoes compensatory adaptive processes giving rise to injury of the first barrier of the local nonspecific resistance. This results in more rapid and severe course of acute pyelonephritis, development of pyodestructive disease, protracted run. Active surgical policy in acute obturation pyelonephritis in patients with a single kidney, early recovery of adequate urine outflow can prevent progression to destructive pyelonephritis and advance treatment results. PMID- 8203068 TI - [Transcutaneous puncture drainage in suppurative destructive diseases of the perirenal cellular tissue]. AB - The authors introduce a new sparing therapy of pyodestructive lesions of the pararenal fat which comprises subcutaneous puncture drainage controlled by ultrasound with subsequent treatment of the purulent focus with a solution of a new antiseptic, sodium hypochlorite. The advantages of the above method over routine approaches include a 1.5-2-fold decrease in the treatment duration, minor traumatism, simplicity, effectiveness in severe conditions. PMID- 8203069 TI - [The ultrasonic diagnosis of renal tuberculosis]. AB - Informative value of ultrasonography potential in the diagnosis of nephrotuberculosis was studied by comparison with conventional x-ray and intraoperative findings in 78 relevant patients. Three patterns of renal ultrasonic architectonics changes in nephrotuberculosis were revealed: 1) focal heterogeneity of renal parenchyma, 2) pseudocystic type, 3) hydronephrotic transformation. It is concluded that ultrasonography is superior to routine diagnostic methods, but is recommended for use in combination with standard methods of phthisiourological diagnosis. PMID- 8203070 TI - [An optimal method for using cyclosporin in the transplantation of cadaveric kidney]. PMID- 8203071 TI - [The pathogenesis of varicocele in children]. PMID- 8203072 TI - [A new method of ureter-sigmoid anastomosis in bladder exstrophy]. AB - A new ureterosigmoidostomy (USS) procedure in exstrophy of the bladder in children comprises establishing a long submucous channel (SC) in the upper or middle third of the sigmoid. This is done by tenial, atraumatic for the mucosa, cut of the sigmoid wall followed by mucosal dissection along the length 2-3 mm larger than the diameter of previously immobilized ureter. After that a special instrument creates upwards an oblique SC, the ureter is placed into the SC opening made in the wall musculoserous layer. Finally, the shunt is established. The same USS procedure was conducted on the other ureter 3-4 cm above the previous shunt. The openings are intubated. Follow-up conducted for 6 years at best showed a complete urine retention existence in 7, a partial one in 1 cases. Radiologically, renal function improved in all the patients. Neither enteropelvic reflex, nor urolithiasis were observed. PMID- 8203073 TI - [The surgical treatment of patients with complex intestinal-urogenital fistulae]. PMID- 8203074 TI - [Staghorn nephrolithiasis]. AB - The authors review the problem of staghorn nephrolithiasis (SN) basing on their experience in the disease diagnosis, treatment and prevention. Basing on the analysis of 2021 cases (1354 females and 667 males), the data on SN etiology and pathogenesis are provided. A complex of diagnostic procedures, an original classification, differentiated indications to various conservative or surgical treatments, trends in prevention of nephrolith reappearance, promising research approaches are outlined. PMID- 8203075 TI - [A method for revascularizing the penis]. AB - The authors propose an original method of vasculogenic impotence surgery involving correction of arterial and arteriovenous insufficiency of the penis. This includes isolation of penile dorsal artery and deep dorsal vein in the proximal and middle third, then of the low epigastric artery along the entire length from the branching to the distal third. Upon establishing the shunt from the dorsal artery and vein, it is sutured with epigastric artery end-to-side. The procedure ends by placing the deep dorsal vein into the duplicature of the corpus cavernosum tunica albuginea. Follow-up results (within 3 years) available for 12 surgical patients demonstrate that improvement did not occur only in one case. This patient had corpus cavernosum sclerosis. PMID- 8203076 TI - [The etiology and pathogenesis of penile oleogranulomas]. AB - The paper reports the experience with surgical treatment of 25 males with penile paraffinomas. A detailed pathomorphological examination of the removed tissues allowed the authors to propose an original idea on the process dynamics upon subcutaneous administration of oily substances. A pathogenetic relationship was established between various stages of chronic inflammation in paraffinoma up to development of rapidly progressing fibrous process the malignancy of which increases in joining infection. The authors advocate early operative interventions instead of long-term conservative therapy in penile paraffinomas complicated by infection. PMID- 8203077 TI - [Extracorporeal shockwave lithotripsy 5 years on]. AB - Investigations initiated in the Research Urological Institute headed by professor N. A. Lopatkin in 1984 on development of an original Russian lithotriptor URAT-II were successfully finished in 1987. Since that time the design has been advanced. The investigators plan to introduce a novel polyfunctional lithotriptor ARKO-LIT with double guidance system and several impulse heads. The unit is to have various forms of impulse generation and diverse physical parameters. When equipped with water cushion, the new lithotriptor will enable the physician to do endoscopic, x-ray diagnostic and therapeutic manipulations. It is emphasized that the main thing in prevention of lithotripsy complications is proper management of the apparatuses which implies sufficient knowledge of the impulse physics and impulse interaction with biologically active tissues. As for cell impairment, lipid peroxidation evaluation suggests that under adequate selection and performance of the procedure as well as proper preoperative preparation, changes in cell membranes are moderate and disappear within 7 posttreatment days. In case of underestimation of the patient's condition, renal function, in violation of the stone destruction technique the above changes may advance to serious and entail severe complications. PMID- 8203078 TI - Astrocytes: form, functions, and roles in disease. AB - Astrocytes, once relegated to a mere supportive role in the central nervous system, are now recognized as a heterogeneous class of cells with many important and diverse functions. Major astrocyte functions can be grouped into three categories: guidance and support of neuronal migration during development, maintenance of the neural microenvironment, and modulation of immune reactions by serving as antigen-presenting cells. The concept of astrocytic heterogeneity is critical to understanding the functions and reactions of these cells in disease. Astrocytes from different regions of the brain have diverse biochemical characteristics and may respond in different ways to a variety of injuries. Astrocytic swelling and hypertrophy-hyperplasia are two common reactions to injury. This review covers the morphologic and pathophysiologic findings, time course, and determinants of these two responses. In addition to these common reactions, astrocytes may play a primary role in certain diseases, including epilepsy, neurological dysfunction in liver disease, neurodegenerative disorders such as Parkinson's and Huntington's diseases, and demyelination. Evidence supporting primary involvement of astrocytes in these diseases will be considered. PMID- 8203079 TI - "Lipomatous" lesions of unknown cellular origin in the liver of B6C3F1 mice. AB - The gross, microscopic, and ultrastructural features of lipomatous lesions in the liver of B6C3F1 mice are described. The cases were selected from a database of 45,406 male and 45,674 female mice used as treated, control, or vehicle-control animals in the National Cancer Institute's Bioassays or the National Toxicology Program's 2-year carcinogenicity studies. Thirteen hepatic lesions identified from cases within the database were re-evaluated microscopically and selected for further study. These lesions were present in ten males and three females that were between 85 and 113 weeks of age at the time of death. Grossly, the liver lesions were described as white to yellow or red to brown nodules/masses or foci that ranged from 2.0 to 25 mm in diameter. The lesions commonly involved the median and left lateral hepatic lobes. Microscopically, many of the lesions closely resembled lipomas described in the liver of human beings, and they consisted of nonencapsulated mature adipose-like tissue with irregular margins. The majority of the cells that comprised the lipomatous lesions were signet-ring shaped. These cells were positive for lipid as evidenced with oil red-O. The lipid droplets were also present within the hepatocytes that comprised the hepatic plates trapped within or surrounding many of the lipomatous lesions. At the margins of many of the lesions there were spindle-shaped cells that contained small intracytoplasmic lipid vacuoles. These cells were often within a stromal matrix that had focal areas of collagen and mucopolysaccharides, as evidenced by weak staining with Masson's trichrome and periodic acid-Schiff's stains, respectively. There was also disruption of the reticulum fibers in many of the lesions, as noted with a Gomori's reticulum stain. Ultrastructurally, cytoplasmic organelles, such as rough endoplasmic reticulum, free ribosomes and small lipid vacuoles, were present in the spindle-shaped cells, whereas signet-ring-shaped cells had few discernible organelles due to peripheral compression of the cytoplasm by single large vacuoles occupying the cytoplasmic space. The spindle shaped cells were free of lysosomes. Thin collagen fibers were seen in contact with some of the spindle-shaped cells and were located between these cells and adjacent hepatocytes, or endothelial cells lining sinusoidal capillaries. A distinct basal lamina was not associated with spindle- or signet-ring-shaped cells. Similar lipomatous lesions were not found in other visceral organs. The exact cellular origin of the hepatic lesions described here is not known. PMID- 8203080 TI - Involvement of canine oral papillomavirus in generalized oral and cutaneous verrucosis in a Chinese Shar Pei dog. AB - Severe papillomatosis developed in the oral cavity and spread throughout the haired skin of the trunk and limbs of an 8-month-old female Chinese Shar Pei dog. The dog had received corticosteroids prior to referral, which was associated with the onset of demodecosis and papillomatosis. Papillomavirus structural antigens were detected in biopsies by immunohistochemistry using a panel of monoclonal and polyclonal antibodies. An 8.2-kilobase papillomavirus-specific DNA molecule was detected in the cutaneous lesions by high stringency Southern blot hybridization using a cloned canine oral papillomavirus DNA probe. Restriction enzyme analysis revealed that the virus in the cutaneous lesions was identical to the canine oral papillomavirus. Discontinuation of the steroids combined with the use of a mitocide, antibiotics, and an autogenous vaccine resolved the demodecosis and papillomatosis. This case report suggests that corticosteroid-induced immunosuppression can expand the tissue tropism of papillomaviruses. PMID- 8203081 TI - Proteinuria associated with glomerulosclerosis and glomerular collagen formation in three Newfoundland dog littermates. AB - Three dogs out of a litter of eight Newfoundland dogs developed a progressive fatal glomerulopathy. The affected dogs were a 2-month-old male, a 2.5-month-old female, and a 1-year-old male. The disease in all three animals was characterized by growth retardation, anorexia, proteinuria (14-16 g/liter), hypoalbuminemia (15 21 g/liter, elevated plasma urea (13-28 mmol/liter), and creatinine (83-296 mumol/liter) concentrations. Because of a bad prognosis the dogs were euthanatized. On postmortem examination, the animals had enlarged, slightly pale kidneys, which revealed glomerulosclerosis and glomerulofibrosis on histologic and electron microscopic examination. The lesions consisted of subendothelial and mesangial collagen fibrils and an increase of mesangial matrix. The fibrosis may result from endothelial or mesangial collagen formation as the manifestation of a metabolic disease. PMID- 8203082 TI - Distribution of antigen in cattle infected with rinderpest virus. AB - Five Holstein heifers (approximately 8 months of age and weighing 225-275 kg) were inoculated subcutaneously with 1,000 TCID50 of rinderpest virus, virulent Kabete O strain. They become clinically ill 2 to 5 days post-inoculation, with fever (40 C to 41.5 C), conjunctivitis, and diarrhea. All were euthanatized when moribund at 6 days postinoculation. The following tissues were collected in formalin, embedded in paraffin, and subsequently subjected to histopathologic and immunohistochemical examination: tongue, buccal mucosa, soft palate, esophagus, rumen, abomasum, duodenum, jejunum with and without Peyer's patch, ileum, cecum, proximal colonic lymphoid patch, spiral colon, eyelid, gall bladder, spleen, tonsil, trachea, lungs, and numerous lymph nodes. Immunohistochemical examination was accomplished using a primary rabbit anti-rinderpest antibody, and either a peroxidase-diaminobenzidine or alkaline phosphatase-Vector Red detection substrate system. In the lymph nodes, spleen, and tonsil, depletion of lymphocytes from all areas was extensive, with antigen most prominent in persisting reticular cells throughout the tissues. In the intestine, necrotizing and ulcerative changes in the mucosa were extensive and widespread. Damage was most severe in areas overlying lymphoid patches. In both small and large intestine, antigen was distributed predominantly in epithelial cells, histiocytic cells in the lamina propria, and in remaining reticular cells of lymphoid patches. In oral mucosa, there were multiple ulcerations and numerous multinucleate syncytial cells, both containing and without antigen. Lungs and trachea had subtle yet consistent necrosis of epithelial cells, with antigen often distributed in a circumferential manner in epithelium of bronchioles. PMID- 8203083 TI - Absence of glomerulonephritis in guinea pigs deficient in the fourth component of complement. AB - Genetically determined deficiencies of the early components of the classical complement pathway (C1, C4, C2) or of the third component of complement (C3) in both human beings and experimental animals are known to be associated with renal disease, including glomerulonephritis. The current study was performed to examine the C4-deficient (C4D) guinea pig for the presence of renal disease. Eighteen C4D animals and 17 control animals (Crl:Hartley) (divided by sex into four age categories) were examined. Light microscopic examination revealed no differences in mesangium, glomerular cellularity, thickness of capillary loops, or presence of epithelial crescents in the kidneys of C4D guinea pigs as compared with control animals. Electron microscopic examination did not reveal glomerular or tubular immune complex deposits in either C4D or control animals. C4D guinea pigs apparently do not demonstrate glomerulonephritis. PMID- 8203084 TI - Flow cytometric DNA ploidy analysis in canine transitional cell carcinoma of urinary bladders. AB - Flow cytometric analysis of DNA ploidy was performed on 51 formalin-fixed, paraffin-embedded samples of canine transitional cell carcinoma of the urinary bladder. The DNA ploidy data obtained were compared to several clinicopathologic features. In addition, the DNA ploidy of 15 hyperplastic/inflamed and 8 normal canine urinary bladders was measured. Forty-three of the 51 neoplastic samples had interpretable DNA histograms. DNA aneuploidy was found in 34/43 (79%) of the transitional cell carcinoma samples. Of the 34 aneuploid neoplasms, 16 (47%) were hyperdiploid, 17 (50%) were tetraploid, and 1 (3%) was hypertetraploid. No significant correlation was found between the presence of DNA aneuploidy and the growth pattern, histologic grade, clinical stage, or individual morphologic features of this neoplasm. Additionally, the DNA ploidy was not related to the sex, age, or survival time of dogs with transitional cell carcinoma. All of the normal and all but one of the hyperplastic/inflamed urinary bladders were diploid. The results from this study demonstrated that DNA ploidy can be measured from paraffin-embedded canine samples by flow cytometry, a majority of the canine transitional cell carcinomas were aneuploid, and a significant correlation did not exist between the DNA ploidy and specific clinicopathologic features of this neoplasm. PMID- 8203085 TI - Acute interstitial pneumonia in mink kits inoculated with defined isolates of Aleutian mink disease parvovirus. AB - The present study addressed the causal role of Aleutian mink disease parvovirus (ADV) in acute interstitial pneumonia in mink kits. All the examined isolates of ADV caused interstitial pneumonia in newborn kits, although the severity of disease and the mortality varied. These findings indicate that ADV is the direct causal agent of this disease in mink kits and that cofactors, which could have been present in the original ADV-K isolate, do not play a role. Acute interstitial pneumonia characterized by hypertrophy and hyperplasia of alveolar type II cells, intranuclear viral inclusions, interstitial edema, and hyaline membrane formation was experimentally reproduced in mink kits infected as newborns with five different isolates of ADV. Four hundred forty-nine newborn mink kits were included in the study, of which 247 were necropsied. The lesions caused by the different isolates were indistinguishable by histopathologic examination, but the incidence (50-100%) and severity (mortality of 30-100%, n = 218) of disease among the mink kits varied. Also, the content of ADV antigens in the lungs of infected kits varied among the groups. According to these features, the examined isolates could be placed in groups of high and low virulence. ADV-K, ADV-Utah I, and ADV-DK were in a highly virulent group producing a mortality of 90-100% (n = 110) in mink inoculated as newborns. ADV-GL and ADV-Pullman belonged to a group of low virulence, with an incidence of clinical disease of 50-70% and a mortality of approximately 30-50% (n = 118) in kits inoculated as newborns. The mortality in the control group receiving a mock inoculum was around 12% (n = 34). The period from infection to development of fatal disease varied from approximately 12 days for the highly virulent isolates up to around 20 days for the isolates of low virulence. The 107 mink kits that survived inoculation with ADV as newborns developed lesions typical of classical Aleutian disease irrespective of the ADV isolate used. The lesions consisted of chronic immune complex-mediated glomerulonephritis and infiltrations with mononuclear cells, including plasma cells in lung, liver, spleen, kidney, mesenteric lymph node, and intestine. Surviving kits also had hypertrophy of the bronchus-associated lymphoid tissue and focal subpleural, intraalveolar accumulations of large cells with foamy cytoplasm, so-called lipid pneumonia. PMID- 8203086 TI - Infected cell types in ovine lung following exposure to bovine respiratory syncytial virus. AB - Sixteen adult sheep (ten females, six males obtained from a closed flock at National Animal Disease Center, Ames, IA) were experimentally infected with bovine respiratory syncytial virus strain 375 (BRSV), and lung tissues were stained for viral antigen. Two infected sheep were euthanatized at each of the following post-inoculation times: 12, 24, 36, 48, 72, 96, 144, and 192 hours. Lung, nasal turbinates, trachea, right cranial bronchial and mediastinal lymph nodes, liver, and spleen were collected for histologic evaluation. An indirect immunoperoxidase technique was performed on routine paraffin-embedded sections of lung tissue, trachea, turbinates, and bronchial and mediastinal lymph nodes to determine the location of the BRSV antigen. For lung tissue from each sheep 400 light microscopic fields at 160x magnification were examined for staining for BRSV antigen. Lung tissue was also collected for virus and bacterial isolation. Daily serum samples were taken for determination of anti-BRSV titers. Severe respiratory disease was not produced in any sheep. Bovine respiratory syncytial virus was isolated from lung tissue collected from all sheep up through 144 hours post-inoculation. At 12 hours post-inoculation (case No. 2) respiratory syncytial virus antigen was detected in bronchiolar epithelium and a mononuclear cell within an alveolar space. Lung tissue from the sheep necropsied between 24 and 144 hours post-inoculation (case Nos. 3-14) contained BRSV antigen in bronchiolar epithelium, type I pneumocytes, type II pneumocytes, alveolar macrophages, and mononuclear cells within alveolar spaces. Macrophages staining for viral antigen were rare. Bronchiolar and type I epithelial cells comprised the majority of infected cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203087 TI - Comparative pathology of a chicken-origin and two duck-origin influenza virus isolates in chickens: the effect of route of inoculation. AB - Forty-nine 5-week-old chickens were inoculated by the intravenous (i.v.), intratracheal (IT), or intranasal (IN) routes with either a chicken-origin or one of two duck-origin type A influenza virus isolates. Twelve control chickens were inoculated with sterile chorioallantoic fluid. For all viruses, i.v. inoculation produced predominate lesions of renal tubule necrosis (nephrosis) and nephritis, and influenza virus nucleoprotein was localized in nuclei and cytoplasm of necrotic renal tubule epithelium. Chickens inoculated by the IT route, and to a lesser extent the IN route, had mild to severe tracheitis, bronchitis, and ventromedial pneumonia associated with secondary bronchi but lacked renal tubule necrosis and nephritis. These data indicate low-virulence avian-origin influenza viruses were nephrotropic during simulated systemic infection (i.v. inoculation) and pneumotropic during simulated local infection (IT and IN inoculation). Gross and histologic kidney lesions produced by i.v. inoculation of the chicken-origin influenza virus were similar to changes reported in outbreaks of low-virulence influenza virus in laying chickens. PMID- 8203088 TI - Adenocarcinoma of the major vestibular gland in a cow. PMID- 8203089 TI - Erythrocyte indices and volume distribution in a dog with stomatocytosis. PMID- 8203090 TI - Unilateral fungal pyelonephritis in a dog. PMID- 8203091 TI - Spontaneous rhabdomyosarcoma in a young Sprague-Dawley rat. PMID- 8203092 TI - Inverted mucoepidermoid papilloma and mucous cell adenocarcinoma of the palpebral conjunctiva in two F344 rats. PMID- 8203093 TI - Coccidioides immitis abortion in an Arabian mare. PMID- 8203094 TI - Iniencephaly and other neural tube defects in a litter of ferrets (Mustela putorius furo). PMID- 8203095 TI - Olfactory ganglioneuroblastoma in a dog: a light, ultrastructural, and immunohistochemical study. PMID- 8203096 TI - Peripheral neuropathy in twin calves. PMID- 8203098 TI - Embryonal rhabdomyosarcoma in a 7-month-old Sprague-Dawley rat. PMID- 8203097 TI - The histologic, ultrastructural, and immunohistochemical characteristics of a thyroid oncocytoma in a dog. PMID- 8203099 TI - Granulomatous enteritis in a pig caused by Mycobacterium avium. PMID- 8203100 TI - Metastasizing adenocarcinoma of the cecum in a squirrel monkey (Saimiri sciureus). PMID- 8203101 TI - Adenocarcinoma arising from gastric heterotopia in the jejunal mucosa of a beagle dog. PMID- 8203102 TI - Rumenoabomasal lesions in steers induced by naturally ingested hair. PMID- 8203103 TI - Adverse drug reaction attributable to aluminum phthalocyanine tetrasulphonate administration in domestic cats. PMID- 8203104 TI - Vaginal stromal polyps in aging rats. PMID- 8203105 TI - Pathologic lesions: they're the worst kind. PMID- 8203106 TI - Humane destruction of horses with a mixture of quinalbarbitone and cinchocaine. AB - One hundred and-two horses requiring to be euthanased for a variety of reasons were killed by the intravenous injection of a mixture of quinalbarbitone sodium (400 mg/ml) and cinchocaine hydrochloride (25 mg/ml). The dose rates used were 1 ml/10, 15, 20 and 30 kg bodyweight, and the time of injection was varied between 5 and 25 seconds. The average time to collapse from the start of the injection was 34 seconds and the average time to clinical death was 230 seconds. Slow injection (particularly of the low dose rates) and premedication with detomidine resulted in a longer time to collapse (median 46 seconds). Premedication with xylazine and low dose rates of the mixture resulted in an unacceptable degree of muscular activity and agonal gasping and death was delayed. Premedication with romifidine and butorphanol resulted in an apparent (but insignificant) reduction in the time to collapse and death but was also accompanied by significant agonal gasping. Without premedication quinalbarbitone and cinchocaine resulted in a smooth and quiet collapse with the cessation of cardiac and respiratory functions within three minutes in all cases, but the palpebral reflex of the horses was prolonged significantly beyond the time when all other reflex activity was lost. Occasional gasping and muscular tremors, particularly of the upper forelimb, occurred particularly when lower dose rates and either very slow or very fast rates of injection were used. One horse which was premedicated with xylazine and received a very low dose at a slow rate showed unacceptably violent muscular activity. At no other time was the procedure regarded as violent or unacceptable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203107 TI - Field study of undifferentiated respiratory disease in housed beef calves. AB - A severe outbreak of undifferentiated respiratory disease affecting 119 of 144 (82.6 per cent) two- to five-month-old housed beef calves was studied by monitoring their clinical signs and rectal temperatures daily or every second day for two months. New cases of respiratory disease, which were first identified three weeks after the calves were housed, occurred over a period of 29 days. The cause of the outbreak was not conclusively determined although 20 per cent of the calves sampled showed serological evidence of recent infection with bovine respiratory syncytial virus and parainfluenzavirus 3. Seventeen of 61 calves (27.9 per cent) which were treated with tilmicosin had to be treated again, compared with nine of 58 calves (15.5 per cent) which were treated with both tilmicosin and flunixin meglumine and did not need further treatment, but this difference was not statistically significant. PMID- 8203108 TI - Spread of Aujeszky's disease virus within pig herds in an intensively vaccinated region. AB - An intensive vaccination programme with the glycoprotein I (gI) and thymidine kinase-deleted vaccine strain 783 was applied on all the pig farms in a region with a high pig density. To monitor the spread of Aujeszky's disease virus within breeding herds in that region, all the breeding stock in nine herds were examined for antibodies to gI six times at intervals of four months. The prevalence of gI seropositive sows decreased greatly in all nine herds. The mean percentage of gI seropositive sows decreased from 56.4 per cent (range 80.0 to 13.6 per cent) at the start, to 20.3 per cent (range 29.1 to 1.6 per cent) after two years. Nevertheless, seroconversions to gI were detected in all the herds, and in six out of the nine breeding herds even during the second year of the study. The intensive regional vaccination apparently did not completely prevent Aujeszky's disease virus infections within these herds. The source of the virus responsible for these infections was not identified. However, because in most herds only a few sows seroconverted, the virus either circulated at a low level within the herds, or its introduction or reactivation did not lead to an extensive spread of the virus. PMID- 8203109 TI - Synergism of ileal symbiont intracellularis and gut bacteria in the reproduction of porcine proliferative enteropathy. PMID- 8203110 TI - Ivermectin in the control of sheep scab. PMID- 8203112 TI - Implementation of poultry meat hygiene regulations. PMID- 8203111 TI - Involvement of lay staff and paraprofessionals in veterinary practice. PMID- 8203113 TI - Locomotor disease in captive young ostriches. PMID- 8203114 TI - Tuberculosis in a cat. PMID- 8203115 TI - Cloning, sequencing, and in vitro expression of glycoprotein gp48 of a noncytopathogenic strain of bovine viral diarrhea virus. AB - Total cellular and viral RNA isolated from cells infected with noncytopathic bovine viral diarrhea virus (BVDV) strain 2724 was used for reverse transcription of viral specific sequences encoding the putative signal sequence and protein encoding region of gp48. The cDNA template was amplified twice by the polymerase chain reaction with a nested set of primers designed from nucleotide sequences of cytopathic BVDV strains NADL and 72, and ligated into a plasmid vector. Nucleotide sequence analysis of the cloned cDNA indicated it was 921 base pairs long, encoded 307 amino acid residues, had high sequence homology to other pestiviruses, and had no significant homology to members of the Flaviviridae. In vitro expression of the cDNA yielded a 30 kDa protein that was precipitated by BVDV polyclonal antiserum. The protein was glycosylated in the presence of canine microsomal membranes to give a 46 kDa product and was secreted into the lumen of the microsomal vesicles. The characteristics of the putative signal peptide were consistent with signal sequences for protein translocation found in eukaryotes. A putative signal peptidase cleavage site was identified at a glycine residue at amino acid position 270. Based on signal peptidase cleavage of gp 48 and lack of a membrane anchor, we proposed that gp48 is a glycosylated protein lacking a transmembrane domain, and is analogous to the glycosylated secreted portion of the pre-M protein of flaviviruses. PMID- 8203117 TI - Vaccination of maternally immune pigs with a live Aujeszky's disease vaccine by coarse spray and other routes. AB - 33 ten weeks old passively immune weaners were inoculated with live, attenuated Aujeszky's disease (AD) vaccine, according to four different vaccination protocols: (groups A/A2) 3 x coarse spray vaccination at 10, 11 and 13 weeks of age, (groups B/B2) 1 x coarse spray at 10 weeks of age followed by 1 x intramuscularly at 13 weeks, (C) 1 x intranasal instillation at 10 weeks of age, and (groups D/D2) 2 x intramuscularly at 10 and 13 weeks of age. A further 10 weaners were included as unvaccinated controls (E/E2). Spray vaccination was technically simple to perform but on average, 20% of subjects were reluctant to expose themselves to the spray. Clinical reactions were absent apart from mild fever in one pig from group B. Weight gains between 10 and 17 weeks of age were slightly lower in group A and group B weaners, compared to control unvaccinated pigs and pigs vaccinated by other routes. Virus neutralising (VN) antibody response was extremely uneven between individuals in groups A and B. Group D pigs vaccinated 2 x intramuscularly showed a 3 week lag in developing high levels of antibody but the intramuscular route, as well vaccination by intransal instillation, proved to be the most dependable technique for inducing uniformly high levels of VN antibody. Challenge with virulent ADV at 17 weeks of age resulted in death from Aujeszky's disease of all five control pigs. One pig in group A which had no VN antibody, also died. All other pigs were protected against death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203116 TI - Reproductive failure in sows following experimental infection with a Belgian EMCV isolate. AB - In this study, a transplacental infection with fetal death was demonstrated following inoculation of pregnant sows with a Belgian encephalomyocarditis virus (EMCV) isolate. Eight multiparus sows were inoculated between 60 and 92 days of gestation with this EMCV-isolate to investigate its ability to cause reproductive failure in sows. Virus persistence and antibody titre in their offspring were also studied. Only the two sows inoculated at 60 days of gestation showed premature farrowing, but all sows seroconverted to EMCV. Virus was recovered from the offspring of all sows at the time of farrowing, but not from every piglet born. One month after birth EMCV could be isolated from all the piglets examined. These results can help in a better understanding of the spread of the disease in piggeries. PMID- 8203118 TI - Isolation of an influenza A virus of unusual subtype (H1N7) from pigs in England, and the subsequent experimental transmission from pig to pig. AB - A novel H1N7 influenza virus (A/swine/Eng/191973/92) was isolated from nasal swabs collected from two pigs on a farm where there had been recent clinical disease due to infection with an H1N1 virus (A/swine/Eng/195852/92). Antigenically, the haemagglutinin (HA) of the H1N7 virus was related most closely to the HA of A/USSR/90/77, whilst the neuraminidase (NA) appeared to be related most closely to the NA of A/equine/Prague/1/56 (H7N7). Pigs infected experimentally with A/swine/Eng/191973/92 developed mild clinical signs, excreted virus into the nasal passages for up to nine days after infection, appeared normal at necropsy, transmitted the virus to sentinel pigs, but seven out of eight pigs failed to seroconvert. These findings suggest that the H1N7 virus has a low pathogenicity for pigs, resulting in limited virus multiplication which is insufficient to stimulate a detectable primary humoral immune response. PMID- 8203119 TI - Antibody response to 146S particle, 12S protein subunit and isolated VP1 polypeptide of foot-and-mouth disease virus type Asia-1. AB - The antibody response to foot-and-mouth disease virus (FMDV) antigens of type Asia-1 in guinea-pigs was studied by micro-serum neutralization test (MSNT) and enzyme-linked immunosorbent assay (ELISA). One inoculation of as little as 1 microgram of binary ethyleneimine (BEI)-inactivated 146S virus particles in guinea-pigs elicited enough neutralizing antibodies to protect them against challenge with virulent virus. However, one inoculation of live 146S virus particles elicited higher levels of neutralizing antibodies in guinea-pigs than that of inactivated 146S particles. One inoculation of 12S protein subunits in guinea-pigs elicited only non-neutralizing anti-12S antibodies detected by ELISA. Similarly, non-neutralizing anti-VP1 antibodies were detected by ELISA after one inoculation of VP1. However, multiple inoculations of 12S or VP1 elicited measurable neutralizing antibodies in guinea-pigs that protected them against challenge. PMID- 8203120 TI - Antibody response to Jembrana disease virus in Bali cattle. AB - An enzyme-linked immunosorbent assay (ELISA) and an agar gel immunodiffusion (AGID) test are described which detected antibody against Jembrana disease virus in infected Bali cattle. Both tests were specific and did not detect antibody in cattle from areas where clinical Jembrana disease has not been detected. The ELISA detected antibody in all infected cattle and had greater sensitivity than the AGID which detected antibody in less than 50% of infected cattle at any single time after infection. The antibody response to the virus was delayed; antibody was not detected by ELISA in a majority of infected cattle until 11 weeks after infection and a maximum antibody response was detected 23 to 33 weeks after infection. Antibody was still detectable 59 weeks after infection. PMID- 8203121 TI - gag- and env-specific serum antibodies in cats after natural and experimental infection with feline immunodeficiency virus. AB - In order to monitor the antibody response to feline immunodeficiency virus (FIV) in cats, following experimental and natural infection, enzyme-linked immunosorbent assays (ELISAs) were developed using recombinant env and gag proteins and p24-specific monoclonal antibodies. It was shown that in experimentally infected cats an env protein-specific antibody response was directly followed by a gag protein-specific response. Furthermore, an ELISA for the detection of env protein-specific serum antibodies proved more sensitive in identifying experimentally and naturally infected cats than ELISAs demonstrating gag protein-specific antibodies. It was concluded that, like in HIV infection of humans, the detection of env protein-specific serum antibodies in addition to gag protein-specific antibodies is not only an important tool in the diagnosis of the infection but also in studies concerning the pathogenesis of the disease. PMID- 8203122 TI - Cloning and sequencing of the chicken anaemia virus (CAV) ORF-3 gene, and the development of an ELISA for the detection of serum antibody to CAV. AB - Chicken anaemia virus (CAV) is a small, unclassified virus involved in anaemia and suspected of causing immunosuppression in young chickens. We have developed an ELISA for the detection of serum antibody to CAV based on cloned antigen. The gene for ORF-3 (the putative capsid protein) was cloned, sequenced and expressed in a bacterial expression system, pGEX. An ORF-3 fusion protein was used to produce an indirect ELISA. PMID- 8203123 TI - Physiological characteristics, antimicrobial susceptibility and serotypes of Pasteurella anatipestifer isolated from ducks in Thailand. AB - Twenty isolates of Pasteurella (Moraxella) anatipestifer from ducks with serositis and septicemia in Thailand between 1988 and 1989 were characterized by various tests. Eighteen isolates fermented glucose and maltose, 3 fructose and 1 each mannose, arabinose, trehalose or sorbitol. All isolates produced gelatinase but not urease, while 2, 3, 5 and 6 produced indole, were CAMP positive, and were proteolytic for milk and coagulated serum respectively. Seven enzymes, phosphatase alkaline, esterase (C4), esterase lipase (C8), leucine arylamidase, valine arylamidase, phosphatase acid and phosphoamidase were detected from all the isolates. The isolates were highly susceptible to ampicillin, erythromycin, penicillin G and tylosin. Gel-diffusion precipitin tests demonstrated that serotype 1 was most prevalent (60%) and serotype 6 followed (5%). Seven isolates (35%) were untypable. These results indicated that P. anatipestifer of serotype 1 played an important role in recent outbreaks of the disease in Thailand. PMID- 8203124 TI - Effect of growth temperature on maintenance of virulent Rhodococcus equi. AB - Repeated passage of virulent Rhodococcus equi ATCC 33701 and L1 at 38 degrees C resulted in attenuation of the strains as a result of curing the virulence plasmid; at 30 degrees C, repeated passage had no such effect. At a temperature of 38 degrees C the plasmid-bearing cells replicated more slowly than their plasmid-cured derivatives and so were gradually replaced by cells lacking plasmids. In contrast, at a temperature of 30 degrees C the growth rate of either strain was not affected by the presence or absence of the plasmid. No plasmid cured derivative was recovered from mouse organs at 48 h after inoculation of a mixture of equal numbers of bacteria with and without plasmids. It is concluded that under nonselective conditions growth temperature is an important factor in maintaining the virulence of R. equi. PMID- 8203125 TI - Protein profiles of Brucella suis and Brucella abortus in isoelectric focusing and sodium dodecyl sulphate-polyacrylamide gel electrophoresis. AB - The protein profiles of five field isolates of Brucella suis and four field isolates of B. abortus were examined. Isoelectric focusing of soluble proteins from cell sonicates produced 28 bands common to both species, with a further 10 bands being unique to a species. No intraspecies variation was detected. Sodium dodecyl sulfate extracted proteins were resolved by polyacrylamide gel electrophoresis. The proteins were transferred to nitrocellulose and then stained. These techniques allowed the demonstration of 35 bands which were common to both species, with a further 15 bands which were unique to one of the two species. Again, no intraspecies variation was detected. PMID- 8203126 TI - Antibody response to Brucella melitensis outer membrane antigens in naturally infected and Rev1 vaccinated sheep. AB - Sera from Brucella infected and B. melitensis Rev1 vaccinated sheep were analysed by immunoblotting using the cell envelope fraction (CEF) of B. melitensis B115. The CEF of B. melitensis B115 was analysed using a bank of monoclonal antibodies. The fraction consisted mainly of S-LPS like molecules, R-LPS and outer membrane proteins (OMPs) of molecular masses of 10, 16.5, 19, 25-27, 31-34, 36-38, 73 and 89 kDa. Immunoblot analysis indicates that the antibody response in infected sheep was mainly directed against the major OMPs of 25-27, 31-34, 36-38 kDa, against 55 to 62, 70-73 and 89 to 94 kDa proteins associated with the CEF and, against S-LPS like molecules. Some infected sheep reacted with antigens of molecular mass lower than 20 kDa. Sera from vaccinated sheep reacted only with OMPs of 36-38, 60, 70-73 and 89 kDa. The major 25-27 and 31-34 kDa OMPs and proteins below 20 kDa were only detected by the sera of infected sheep. These differences may be due to the persistence of the field infection also reflected by the fact that antibody response against O-polysaccharide (O-PS), as measured by enzyme-linked immunosorbent assay (ELISA), was more intense in infected sheep than in vaccinated ones. These results also indicate that these OMPs could be useful to differentiate B. melitensis infection from B. melitensis Rev.1 vaccination in sheep. PMID- 8203127 TI - Immunoblot studies in the differential diagnosis of porcine brucellosis: an immunodominant 62 kDa protein is related to the mycobacterial 65 kDa heat shock protein (HSP-65). AB - Smooth Brucella spp. share certain lipopolysaccharide antigens with other bacteria, resulting in serological cross-reactions which can prevent the definitive diagnosis of brucellosis. To identify other antigens with serodiagnostic potential, immunoblot studies following sodium dodecyl sulphate polyacrylamide gel electrophoresis were carried out. Sera from pigs experimentally infected with Brucella suis and naturally infected feral pigs, sera from pigs from a farm with a known history of Yersinia enterocolitica 0:9 infection, Brucella Complement Fixation Test (CFT) reactor pigs (aetiology unknown) and pigs from consistently Brucella CFT negative farms were examined. Although B. suis infected pigs recognized a total of nine B. melitensis antigens, individual pigs rarely recognized more than three antigens in the range. A 62 kDa antigen was recognized by the majority (73%) of the Brucella infected pigs, but only by 10 to 23% of pigs from the other groups. This antigen was shown to be the Brucella homologue of the ubiquitous 65 kDa heat shock protein (HSP-65) family by immunoblot studies with 14 monoclonal antibodies to the Mycobacterium leprae HSP 65. Only four of these monoclones (Y1.2, ML-30, D7C and IIIC8) identified the B. melitensis 62 kDa protein suggesting that unshared, potentially Brucella specific, regions exist. Sera from Y. enterocolitica 0:9 infected pigs, CFT reactor pigs (aetiology unknown), CFT negative pigs and hyperimmune pig serum raised to Y. enterocolitica 0:9 also recognized B. melitensis antigens, most notably a 17 kDa protein. This antigen appears to be a common cross-reactive protein. PMID- 8203128 TI - Comparative histopathology of draining lymph node after infection with virulent or attenuated strains of Salmonella abortusovis in lambs. AB - Histological responses to the early phase of infection were compared in parotid lymph nodes of lambs infected by the subcutaneous route into the right eyelid with either a virulent or an attenuated strain of Salmonella abortusovis. The right parotid lymph nodes showed a massive PMN infiltration for the first days of infection for both strains. From day 6, the infected lymph nodes developed a lymphoid hyperplasia with prominent germinal centers independent of strain type. The virulent strain of S. abortusovis induced focal lesions in 2 out of 6 lambs necropsied on days 6 and 10, and provoked a systemic infection evidenced by the regular colonization of spleen on day 6. In contrast, no focal lesion and a restricted bacterial dissemination were observed in lambs infected with the vaccinal strain. PMID- 8203129 TI - Protection of mice and swine against infection with Actinobacillus pleuropneumoniae by vaccination. AB - CaCl2 and LiCl cell extracts and a crude hemolysin preparation were isolated from Actinobacillus pleuropneumoniae serotype 1 strain 4074 and tested for protection against A. pleuropneumoniae serotype 1 and 5 in mice. The LiCl cell extract adsorbed on AlPO4 and the crude hemolysin preparation adsorbed on Al(OH)3 showed a highly significant protection (P < 0.01) against both serotypes. Different vaccine preparations were used to immunize pigs by intra-muscular injection at days 0 and 14; the pigs were then challenged at day 21 by intra-tracheal inoculation of 1 x 10(8) colony forming units (CFU) of a serotype 1 strain 4074. A vaccine which combined the LiCl extract and the crude hemolysin preparation adsorbed on Al(OH)3 gave the best protection with no mortality and no sign of morbidity in the vaccinated pigs. In the other experimental groups which included a group immunized with a commercial bacterin, mortality, respiratory disease and extensive pulmonary lesions were noted. This mixture shows good potential as a vaccine against pleuropneumonia in pigs. PMID- 8203130 TI - Serotypes of bovine Escherichia coli producing cytotoxic necrotizing factor type 2 (CNF2). AB - The serotypes of 101 faecal bovine necrotoxigenic Escherichia coli (NTEC) producing the cytotoxic necrotizing factor type 2 (CNF2) were determined. Although, NTEC producing CNF2 belonged to 48 different O:K:H serotypes, only eleven of them accounted for 54% of strains. The most common serotypes in order of frequency were: O123:K-:H16, O3:K-:H21, O88:K-:H8, O15:K14:H21, O1:K-:H12, O1:K1:H46, O2:K1:H5, O55:H21, O88:K?:H25, O117:K?:H21 and O123:K-:H-. The serotypes of CNF2 NTEC were different from those found in NTEC producing CNF1 and in enterotoxigenic, verotoxigenic, enteropathogenic, enteroinvasive and enteroadherent E. coli strains that cause infections in humans and animals. PMID- 8203131 TI - Lymphocyte responses to viral antigens and phytohaemagglutinin in persistently viraemic sheep and lambs experimentally infected with Border disease virus. AB - Lymphocytes obtained from lambs 5 to 21 days after experimental infection with Border disease virus (BDV) showed significant blastogenic responses to live or inactivated BDV. Live virus stimulated significantly higher lymphocyte transformation (LT) responses than inactivated virus. Lymphocytes obtained from uninfected control and persistently infected lambs had no significant response to live or inactivated antigen. Lymphocyte responses to phytohaemagglutinin were significantly higher in control lambs than in experimentally infected lambs in samples obtained 5 to 10 days post-inoculation. PMID- 8203133 TI - [Preliminary experiments on the mode of action of oxalysine on Candida albicans and C. parapsilosis]. AB - Oxalysine, [formula: see text] is a novel anti-fungal antibiotic isolated from Streptomyces roseoviridofuscus n. sp.. MIC values 0.8-3.1 micrograms/ml suggested a good activity of oxalysine against Candida parapsilosis when compared to Amphotericin-B and 5-Fluorocytosine. The MIC for Trichophyton rubrum and Microsporeum gypseum range from 1.56-3.13 micrograms/ml. Transportation of radioactivity labelled (3H)-Lysine compete with oxalysine was used to characterize Lysine permease in Candida albicans. The results showed that oxalysine 10-folds did not reduce the rate of (3H)-Lysine uptake. This showed low affinity of lysine permease to oxalysine in Candida albicans. When the leakage of U V 260 nm-absorbing materials was used as the evidence of permeability of the cell membrane. Oxalysine was not observed to cause leakage of cellular constituents. The result showed that the action of oxalysine is not on the cell membrane of the microorganism. The incorporations of (14C)-Methione and (14C) Adenine were used as a method of measuring the antimicrobial action of the drug oxalysine is on protein and/or nucleic acid synthesis. It was found that oxalysine 0.4 mmol/L did not significantly inhibit their incorporations into protein and/or DNA, but strongly inhibit the incorporation of (14C)-Adenine into RNA. PMID- 8203134 TI - Research in pastoral care. PMID- 8203132 TI - Prevalence of P types among porcine rotaviruses using subgenomic VP4 gene probes. AB - Nucleic acid probes were developed to differentiate VP4 (P) types among porcine rotaviruses. These probes were then used to determine the relative prevalence of P types 6 (Gottfried-like) and 7 (OSU-like) in cultivated rotaviruses and field specimens. The variable regions between bases 205-551 of the VP4 gene of rotavirus strains OSU and Gottfried were amplified by the polymerase chain reaction and radiolabeled with 32P by random primer extension. Radiolabeled probes were tested in a dot blot hybridization assay. The subgenomic probes prepared from VP4 gene detected as little as 5 ng oF rotavirus RNA and were specific for differentiating the two porcine rotavirus P types. The probes were used to determine the P type of several reference rotavirus strains and recently cultivated porcine rotavirus strains. Eight of the 10 cultivated, previously untyped, rotaviruses isolates tested were of P type 7 (OSU-like). Two rotavirus strains neither reacted with OSU nor with the Gottfried probe, therefore, their P type could not be determined. Seventeen out of the 26 rotavirus (65.4%) field samples tested had a P type 6 (Gottfried-like) whereas 5 out of 26 (19.2%) had a P type 7 (OSU-like). Four of the 26 samples (15.4%) reacted neither with the OSU nor with the Gottfried probe and possibly represent previously unrecognized P types in swine. Data in this study suggests that (1) rotaviruses with P type 7 are most common among the cultivated rotaviruses, (2) rotaviruses with P type 6 are the most abundant type of rotavirus in natural infections and (3) rotaviruses with additional P types are also associated with diarrheic swine. PMID- 8203135 TI - Things that help and hinder adolescent sibling bereavement. AB - A taxonomy of the things that help and hinder adolescents' sibling bereavement was developed from the responses of 140 bereaved adolescents to the questions What helped you cope with your sibling's death? and What made it harder to cope with your sibling's death? The dichotomous taxonomic framework revealed five categories. The categories of self, family, friends, social system, and time contained descriptions of things that helped coping. The categories of self, family, and social system also included descriptions of things that hindered coping with sibling grief. Support considered helpful was perceived as "people being there for me." Support that was considered as not helpful (insensitive) was perceived as "people not being there for me." Two themes emerged from the data. The theme of resourcefulness pervaded each of the helped categories and served to increase the adolescents' sense of resiliency. The theme of helplessness pervaded the three hindered categories and created a sense of vulnerability. PMID- 8203136 TI - Family stress, social support, violence, and sons' behavior. AB - Although the low income, female-headed, inner-city family has been repeatedly linked to child behavior problems, the family processes related to child misbehavior in this high risk group have not been identified. In a group of predominantly African American inner-city low-income mothers who lived alone with their children, the relationships between family stress, social support, mothers' conflict resolution tactics, and sons' behavior were examined using the family stress adaptation model, and potential nursing interventions were identified. The sample of low-income, inner-city mother-alone families reported more family stress and less social support than normative White Anglo-Saxon Protestant families. Family violence rates did not differ between the sample and nationally representative normative groups. Thirty-nine percent of sons, referred to the study because of school difficulties, were reported to have behavior problems requiring additional assessment. Analysis confirmed the fit of sample data to the model and identified family stress as the best site for nursing intervention for these high-risk families. PMID- 8203137 TI - A measure of perceived environmental uncertainty in hospitals. AB - The purpose of this study is to evaluate the preliminary psychometric properties of the Perceived Environmental Uncertainty Questionnaire (PEUQ). Environmental uncertainty (EU) refers to times when within the organization unanticipated events and problems occur with frequency and cannot be predicted by members of the organization due to a lack of critical information. The PEUQ was designed as a measure of EU and was tested with 375 patient-care and nonpatient-care hospital employees. Internal consistency as measured by Cronbach's alpha was .81. Confirmatory factor analysis supported two of the PEUQ's hypothesized three factors: state and effect EU. These two factors accounted for 61.1% of the variance in subjects' level of uncertainty. Factor analysis failed to confirm response uncertainty as a subconstruct of EU. Contrasted group analysis found expected differences in the level of perceived EU between workers on different hospital units (t = -5.02, p < .001). This study provides evidence of the PEUQ's beginning reliability and validity as a measure of EU. Failure to identify response uncertainty as a salient subconstruct of EU warrants further exploration. The design of nursing care delivery structures (NCDS) to minimize EU first requires a means to measure hospital units' EU. The establishment of the PEUQ's psychometric soundness is antecedent to measuring EU and improving the efficacy of our NCDS. PMID- 8203138 TI - Psychosocial aspects of chronic lower leg ulceration in the elderly. AB - The perceived health of a group of elderly people with chronic lower leg ulceration was compared with health perceptions of a matched group of controls. The perceived psychological well-being, self-esteem, life satisfaction, and social supports of the two groups were also compared. The people with leg ulceration described significantly more problems with activity and mobility, pain, and health worries and concerns than the control group. The groups did not differ significantly in their general evaluations of their health status, the experience of physical symptoms, or the numbers of diagnosed medical problems present. The leg ulcer group reported significantly lower levels of self-esteem and higher levels of negative affect, but the groups did not differ significantly on the other psychological variables. Leg ulcers are a serious problem for those affected by them, and health care providers need to be more informed about the effect of chronic health problems on elderly persons. PMID- 8203139 TI - Predictors of nurses' involvement in research activities. AB - Practicing nurses who have special expertise concerning clinical problems generally have minimal involvement in clinical nursing research. As a step toward increasing their research participation and, therefore, the relevancy of clinical studies, this study surveyed 1,217 nurses employed at nine health care agencies concerning their research attitudes, work environment, and research involvement. Descriptive statistics indicated that nurses value nursing research and want more time for research-related activities. Discriminant function analysis revealed that prior research instruction, awareness of support for research, and positive attitudes toward research were predictive of nurses' participation in research activities. PMID- 8203140 TI - Moving toward a nursing model in advanced practice. AB - The nurse practitioner focus has been evolving from a medical to a nursing orientation since the inception of the role in 1965. The purpose of this study was to examine relationships between role attitudes and values, confidence about practice knowledge and skills, and orientation to a medical or nursing model to guide practice. A national random sample of 482 nurse practitioners completed the Attitudes and Values Scale, the Confidence in Skills Scale, and a demographic survey. Findings indicate that nurse practitioners are very confident about their practice skills and knowledge and have a very strong nursing orientation. There is a direct positive correlation between level of confidence and degree of nursing orientation. Nurses in the sample also rated themselves as more confident about hands-on skills than indirect role components such as utilization of research, change theory, and evaluation of practice outcomes. The discussion interweaves this study's findings with role theory and offers a comparison and contrast to the existing body of knowledge. PMID- 8203141 TI - Evaluation of breast self-examination beliefs using a decision model. PMID- 8203142 TI - Strategies for teaching nursing research. Discovering the creative listening hole. AB - Creative questioning that is based on nonverbal inner listening can lead to new insights, discoveries, and perspectives. Though very challenging, the mythology of reaching the listening hole can help the student develop an ear for keys or gaps in his or her perceptions about phenomena. It can help develop respect for the rich lode of nursing experience from which researchable questions can be developed. Finally, creative research questioning introduces a new mental discipline that can lead to a fresh perception of nursing practice questions. The value of the process outweighs the risks and difficulties. PMID- 8203143 TI - WHO Expert Committee on Biological Standardization. PMID- 8203144 TI - Inhibition of protein synthesis disrupts the Golgi apparatus in the fission yeast, Schizosaccharomyces pombe. AB - Schizosaccharomyces pombe was treated with either cycloheximide or anisomycin at levels sufficient to inhibit > 95% of protein synthesis for periods upon to 3 h, equivalent to one cell cycle. Treatment for as little as 1 h caused significant loss of the Golgi apparatus by both immunofluorescence and electron microscopy. The loss was quantitated by stereology on electron micrographs. Nearly 90% of the stacked Golgi was lost over a 3 h period. No other intracellular membrane compartment seemed to be affected. Measurement of enzyme activities confirmed these observations. The activity of a resident of the Golgi apparatus, alpha-1,2 galactosyltransferase, was reduced over this time, whereas the endoplasmic reticulum marker, BiP, and the cytoplasmic enzyme, hexokinase, were unaffected. The morphological changes associated with cycloheximide addition were reversed on its removal, though there was a lag before cells recommenced growth or secretion of the enzyme, acid phosphatase. PMID- 8203145 TI - Characterization of the KIN2 gene product in Saccharomyces cerevisiae and comparison between the kinase activities of p145KIN1 and p145KIN2. AB - We have isolated two yeast genes, KIN1 and KIN2, by their homology to the protein kinase family of viral oncogenes. Previous studies have identified the yeast KIN1 gene product (pp145KIN1) as a 145 kilodalton (kDa) phosphoprotein with serine/threonine-specific protein kinase activity. To identify and biochemically characterize the KIN2 gene product, antibodies were raised against a bacterial beta-galactosidase/KIN2 fusion polypeptide. In vivo, the KIN2 gene product is a 145 kDa phosphoprotein, pp145KIN2. In immune complexes, pp145KIN2 demonstrates serine/threonine protein kinase activity, transferring phosphate from [gamma 32P]ATP to either itself or the exogenously added substrates alpha-casein, acid denatured enolase, or phosvitin. In vitro, kinase activity is dependent on either Mn2+ or Mg2+ ions. Both enzymes, pp145KIN1 and pp145KIN2, prefer ATP over GTP as their phosphoryl donor. Since a new class of yeast protein kinases has been identified which are serine/tyrosine-specific, we analysed a wide range of substrates to see if any could be phosphorylated by pp145KIN1 or pp145KIN2 on tyrosine residues. Both enzymes phosphorylate alpha-casein, acid-denatured enolase, and phosvitin on serine and threonine residues. Neither enzyme could phosphorylate tyrosine residues even though good substrates for tyrosine-specific kinases such as enolase, angiotensin II, and the synthetic polymer GLU80TYR20 were used. The biochemical analysis of KIN2 kinase activity shows remarkable similarity to that of its most closely related yeast kinase, KIN1. It remains to be seen if these two yeast protein kinases share any functional relationships or substrates in vivo. PMID- 8203146 TI - Analysis of an 11.7 kb DNA fragment of chromosome XI reveals a new tRNA gene and four new open reading frames including a leucine zipper protein and a homologue to the yeast mitochondrial regulator ABF2. AB - We report the nucleotide sequence of an 11.7 kb fragment from the left arm of Saccharomyces cerevisiae chromosome XI. Analysis reveals a new tRNA for valine and four unknown open reading frames among which YKL245 shows homology with a yeast mitochondrial regulatory protein and YKL244, YKL246 and YKL247 are unknown. PMID- 8203147 TI - Analysis of the rad3-101 and rad3-102 mutations of Saccharomyces cerevisiae: implications for structure/function of Rad3 protein. AB - The mutations rad3-101 and rad3-102 (formerly rem1-1 and rem1-2) of the essential RAD3 gene of Saccharomyces cerevisiae confer a phenotype of semidominant enhancement of spontaneous mitotic recombination and mutation frequencies, but not extreme sensitivity to ultraviolet (UV) light. These properties differ from the previously published observations of other rad3 mutations, which are very UV sensitive but do not alter recombination frequencies significantly. We have located the position of DNA sequence changes from wild-type RAD3 to the rad3-101 and rad3-102 mutations and have demonstrated that these sequence changes are necessary and sufficient to confer the (Rem-) mutant phenotype when transferred into otherwise wild-type RAD3 plasmids. The Rem- mutations are not located in the same region. It is possible that the two regions of the gene in which these mutations map define portions of the molecule which are in contact when folded in the native configuration. To begin to test this hypothesis, we have constructed two double mutant alleles, one with rad3-101 and rad3-102, and one with the UV sensitive rad3-1 mutation and rad3-102. We find that plasmids carrying these double mutant alleles of RAD3 are no longer able to confer a hyper recombinational phenotype and do not complement the UV-sensitivity of the excision-defective rad3-2 allele. We conclude that the double mutant alleles are non-functional for excision repair, and may be null. We have also constructed new rad3 alleles by oligonucleotide-directed mutagenesis and have tested their effects on spontaneous mutation and mitotic recombination and on UV repair. PMID- 8203149 TI - Current awareness on yeast. PMID- 8203148 TI - Sequence of a 4.8 kb fragment of Saccharomyces cerevisiae chromosome II including three essential open reading frames. PMID- 8203150 TI - Extracellular levansucrase of Bacillus subtilis produced in yeast remains in the cell in its precursor form. AB - Levansucrase, a Bacillus subtilis extracellular enzyme, was not secreted in the culture medium when produced in yeast. The protein accumulated inside the cell in its precursor form which represented 0.3% of total proteins. The absence of any post-translational modifications, such as signal sequence cleavage or addition of N-linked sugars, indicated that this protein did not enter the reticulum secretion pathway. Direct observation of the cells by confocal laser scanning microscopy showed that levansucrase was associated with the cytoplasmic membrane. Subcellular fractionation experiments revealed that levansucrase precursor form is associated with membranes through weak ionic interactions. The purified precursor displayed the same catalytic properties as levansucrase secreted by B. subtilis. Thus yeast could be used as a source of levansucrase precursor allowing its isolation as a pure form on a milligram scale. PMID- 8203151 TI - A physical comparison of chromosome III in six strains of Saccharomyces cerevisiae. AB - We have tested the clones used in the European Yeast Chromosome III Sequencing Programme for possible artefacts that might have been introduced during cloning or passage through Escherichia coli. Southern analysis was performed to compare the BamHI, EcoRI, HindIII and PstI restriction pattern for each clone with that of the corresponding locus on chromosome III in the parental yeast strain. In addition, further enzymes were used to compare the restriction maps of most clones with the map predicted by the nucleotide sequence (Oliver et al., 1992). Only four of 506 6-bp restriction sites predicted by the sequence were not observed experimentally. No significant cloning artefacts appear to disrupt the published sequence of chromosome III. The restriction patterns of six yeast strains have also been compared. In addition to two previously identified sites of Ty integration on chromosome III (Warmington et al., 1986; Stucka et al., 1989; Newlon et al., 1991), a new polymorphic site involving Ty retrotransposition (the Far Right-Arm transposition Hot-Spot, FRAHS) has been identified close to CRY1. On the basis of simple restriction polymorphisms, the strains S288C, AB972 and W303-1b are closely related, while XJ24-24a and J178 are more distant relatives of S288C. A polyploid distillery yeast is heterozygous for many polymorphisms, particularly on the right arm of the chromosome. PMID- 8203152 TI - Transport of hexoses in yeast. Re-examination of the sugar phosphorylation hypothesis with a new experimental approach. AB - The constitutive transport of hexoses in yeast has been re-examined with a new radioactive experimental approach devised to distinguish between association or independence of the transport step with phosphorylation of the sugar substrate. The approach takes advantage of the fact that the label of [2-3H]mannose disappears once it has been phosphorylated by the yeast, due to its conversion to fructose-6-phosphate. Our results with wild-type yeast and this fermentable sugar support the view that the transport of hexoses in yeast does not involve phosphorylation of the substrate. Other features of the transport process have been examined using this experimental procedure and are also reported. PMID- 8203153 TI - Cloning, nucleotide sequence and functions of XPR6, which codes for a dibasic processing endoprotease from the yeast Yarrowia lipolytica. AB - Yarrowia lipolytica DO613, carrying the xpr6-13 mutation, secretes an inactive precursor of alkaline extracellular protease that has not been cleaved after the Lys-Arg at the end of the pro-region. Compared to wild type, DO613 membrane preparations had significantly reduced ability to cleave after Lys-Arg of an artificial substrate. The XPR6 gene was cloned by complementation by screening for restoration of production of alkaline protease activity. Sequencing of a 3735 base pair SalI-SphI XPR6 fragment revealed a large open reading frame with a coding capacity of 976 amino acids (molecular weight, 110,016). The deduced amino acid sequence had significant homology to Saccharomyces cerevisiae Kex2p, a processing endoprotease that cleaves after pairs of basic amino acids. Disruption of the XPR6 gene was not lethal, but it resulted in several phenotypic changes. First, essentially no mature alkaline extracellular protease was produced indicating that the low levels produced by strains carrying previously isolated xpr6 alleles were due to leaky mutations. Second, mating type B strains carrying the disrupted XPR6 gene did not mate, but mating type A strains did. Third, the XPR6 disruption strains grew poorly on rich media at pH 5.5 and above. Cells remained physically attached after budding and continued to bud forming large dog balloon-like structures. In addition, these structures aggregated forming visible clumps in liquid culture. These growth aberrations were largely eliminated by growing cells in medium at pH 4. Fourth, no mycelial forms were observed regardless of the pH. PMID- 8203154 TI - Molecular characterization of the SPT23 gene: a dosage-dependent suppressor of Ty induced promoter mutations from Saccharomyces cerevisiae. AB - SPT genes are suppressors of mutations induced by the retrotransposon Ty in Saccharomyces cerevisiae. All SPT genes isolated to date suppress Ty-induced mutations by altering transcription. SPT23 was identified as a multicopy suppressor of the Ty-induced promoter mutations his4-912 delta and lys2-61. Multicopy expression of SPT23 suppresses a variety of Ty-induced promoter mutations, including the MAT-regulated alleles his4-917(480) and lys2-173R2. Here, we report the initial characterization of the SPT23 gene, including its nucleotide sequence and location in the yeast genome. The SPT23 gene contains a 1854 base pair open reading frame. Searches of the current data bases show no homology between SPT23 and previously described genes or proteins. The SPT23 gene is located between RAM2 and MAK11 on the left arm of chromosome XI. Tn10-LUK insertional mutagenesis of the SPT23 gene indicates that SPT23 is not essential for vegetative growth and spt23 mutations do not confer an Spt- phenotype. PMID- 8203155 TI - Transformation-associated recombination between diverged and homologous DNA repeats is induced by strand breaks. AB - Rearrangements within plasmid DNA are commonly observed during transformation of eukaryotic cells. One possible cause of rearrangements may be recombination between repeated sequences induced by some lesions in the plasmid. We have examined the mechanisms of transformation-associated recombination in the yeast Saccharomyces cerevisiae using a plasmid system which allowed the effects of physical state and/or extent of homology on recombination to be studied. The plasmids contain homologous or diverged (19%) repeats of the URA3 genes (from S. cerevisiae or S. carlsbergensis) separated by the genetically detectable ADE2 colour marker. Recombination during transformation for covalently closed circular plasmids was over 100-fold more frequent than during mitotic growth. The frequency of recombination is partly dependent on the method of transformation in that procedures involving lithium acetate or spheroplasting yield higher frequencies than electroporation. When present in the repeats, unique single strand breaks that are ligatable, as well as double-strand breaks, lead to high levels of recombination between diverged and identical repeats. The transformation-associated recombination between repeat DNAs is under the influence of the RAD52 and RAD1 genes. PMID- 8203156 TI - Selectable marker replacement in Saccharomyces cerevisiae. AB - Selectable markers integrated by the 'gamma' deletion method (Sikorski and Hieter, 1989) can be efficiently replaced in vivo with other markers by transformation with homologous plasmids. Transformation frequencies in experiments designed to replace original selectable markers with an alternate marker were high and molecular analysis confirmed that all transformants that exhibited the expected phenotypes (loss of the original prototrophy and gain of the alternate prototrophy) resulted from homologous recombination between plasmid sequences at the target locus. This technique involves no plasmid construction and greatly facilitates the generation of yeast cells containing multiple gene disruptions. PMID- 8203157 TI - Ribosome synthesis during the growth cycle of Saccharomyces cerevisiae. AB - We have measured the content of ribosomes, the rate of synthesis of ribosomal RNA, and the level of the mRNA for ribosomal proteins as a culture of Saccharomyces cerevisiae passes through the growth cycle. The transcription of both ribosomal RNA and ribosomal protein genes disappears at an unexpectedly early stage in the growth cycle, accompanied by a decline in the total RNA content of the culture by nearly 50% and a decline in the number of ribosomes per cell to less than 25% of the maximum value. During this time the cells continue to grow through more than two doublings, initially at the normal log growth rate, which then decline gradually for several hours. The data suggest that the cell can sense an unfavorable change within the medium and responds by employing regulation of both synthesis and degradation of its ribosomes. We conclude that the cell regulates ribosome synthesis and content according to its estimate of the potential for growth. PMID- 8203159 TI - Structural modification of spindle pole bodies during meiosis II is essential for the normal formation of ascospores in Schizosaccharomyces pombe: ultrastructural analysis of spo mutants. AB - In order to characterize the morphological steps defined by sporulation (spo) genes during the formation of ascospores in the fission yeast Schizosaccharomyces pombe, we performed an electron microscopic study of the ultrastructure of the spindle pole body (SPB) and of the development of the forespore membrane during the second meiotic division (meiosis II) in sporulation-deficient (spo) mutants (spo4, spo5, spo14 and spo18). No difference was found in terms of the function and the structure of the SPB during the first meiotic division (meiosis I) between the four mutants and wild-type cells. However, during meiosis II, the spo4 and spo18 mutants underwent nuclear division but in neither case were the SPBs modified nor were forespore membranes formed. The SPBs of the spo18 mutant diminished in size after meiosis II and eventually disappeared after 18 h in sporulation medium. By contrast, the SPBs of the spo4 mutant remained unchanged even after an 18-h incubation. The outer plaques of SPBs of spo5 and spo14 mutants were sufficiently modified to allow them to initiate development of the forespore membrane, but the membrane had an abnormally expanded lumen and did not enclose the nuclei during meiosis II. The spo5 mutant produced anucleate spore like bodies while the spo14 mutant formed unorganized structures with irregular peripheries which, presumably, contained spore-wall precursors, instead of anucleate spore-like bodies. We conclude that the modification of the SPB is essential for the formation of ascospores and at least two genes (spo5 and spo14) participate in the development of the forespore membrane. The defective phenotypes define discrete steps in the development of ascospores, which proceeds via steps defined by the mutant spo4, spo18, spo14 and spo5 genes respectively. Our observations provide further substantial evidence that the SPB plays a pivotal role in the normal development of ascospores in yeasts. PMID- 8203158 TI - A homologous cell-free system for studying protein translocation across the endoplasmic reticulum membrane in fission yeast. AB - We report the development of a homologous in vitro assay system for analysing translocation of proteins across the endoplasmic reticulum (ER) membrane of the fission yeast Schizosaccharomyces pombe. Our protocol for preparing an S. pombe extract capable of translating natural messenger RNAs was modified from a procedure previously used for Saccharomyces cerevisiae, in which cells are lysed in a bead-beater. However, we were unable to prepare fission yeast microsomes active in protein translocation using existing budding yeast protocols. Instead, our most efficient preparations were isolated by fractionating spheroplasts, followed by extensive washing and size exclusion chromatography of the crude membranes. Translocation of two ER-targeted proteins, pre-acid phosphatase from S. pombe and prepro-alpha-factor from S. cerevisiae, was monitored using two distinct assays. First, evidence that a fraction of both proteins was sequestered within membrane-enclosed vesicles was provided by resistance to exogenously added protease. Second, the protected fraction of each protein was converted to a higher molecular weight, glycosylated form; attachment of carbohydrate to the translocated proteins was confirmed by their ability to bind Concanavalin A Sepharose. Finally, we examined whether proteins could be translocated across fission yeast microsomal membranes after their synthesis was complete. Our results indicate that S. cerevisiae prepro-alpha-factor can be post translationally imported into the fission yeast ER, while S. pombe pre-acid phosphatase crosses the membrane only by a co-translational mechanism. PMID- 8203160 TI - A general model of yeast energy metabolism in aerobic chemostat culture. AB - The pattern of energy metabolism of different types of yeasts (obligate aerobes and facultative anaerobes) in aerobic chemostat cultures has been evaluated and interpreted on the basis of a coupling of metabolic fluxes between glycolytic and oxidative components. A model has been formulated which defines glycolytic and oxidative subunits through which the substrate C-flux (gram-atom g-1 h-1) is calculated, stating that a relative imbalance between glycolytic flux and subsequent oxidative steps alone is sufficient to account for the onset of oxidoreductive metabolism in any type of yeast, irrespective of the maximum respiratory capacity. The model is able to reproduce the patterns of behaviour reported for the different types of yeasts, and the individual features of each strain are explained on the basis of metabolic differences which are defined by a set of normalized parameters. The model can be applied to different substrates and conditions, providing a methodological basis for more detailed studies of the steps controlling yeast energy metabolism. PMID- 8203161 TI - Analysis of PFK3--a gene involved in particulate phosphofructokinase synthesis reveals additional functions of TPS2 in Saccharomyces cerevisiae. AB - The pfk3 mutation of Saccharomyces cerevisiae causes glucose-negativity in a pfk1 genetic background, the mutant is temperature-sensitive for growth and homozygous diploids do not sporulate. It fails to accumulate trehalose, and has an altered glycogen accumulation profile under glucose-starvation conditions. pfk3-6, one of the alleles of pfk3, has an altered morphology, forming long chain-like structures at 36 degrees C. The PFK3 gene was cloned by complementation of the mutant phenotypes. Integrative transformation demonstrated that the complementing fragment encoded the authentic PFK3 gene. The disruption of the gene does not affect viability. Like the EMS-induced pfk3 mutant, the disruptants are temperature-sensitive and in a pfk1 genetic background are also glucose-negative. The PFK3 transcript is induced by heat-shock. Partial DNA sequence shows that PFK3 is identical to TPS2 (De Virgilio et al., 1993). We demonstrate that, apart from being a structural determinant of trehalose 6-phosphate phosphatase, PFK3 (TPS2) is required for PFKII synthesis and normal regulation of S. cerevisiae response to nutrient and thermal stresses. PMID- 8203162 TI - Molecular cloning and analysis of the yeast flocculation gene FLO1. AB - The DNA sequence of the flocculation gene FLO1 of Saccharomyces cerevisiae, which is located on chromosome I (Watari et al., 1989) was determined. The sequence contains a large open reading frame (ORF) of 2586 bp and codes for a protein of 862 amino acids. However, further study (genomic Southern and polymerase chain reaction analyses) indicated that the gene we cloned was not the intact FLO1 gene but a form with an approximately 2 kb deletion in the ORF region. The intact FLO1 gene was then cloned and its nucleotide sequence determined. The sequence revealed that the ORF of the intact gene is composed of 4611 bp which code for a protein of 1537 amino acids. A remarkable feature of the putative Flo1 protein is that it contains four families of repeated sequences composed of 18, 2, 3 and 3 repeats and that it has a large number of serines and threonines. In the deleted FLO1 form, a large part of these repeated sequences was missing. The N- and C terminal regions are hydrophobic and both contain a potential membrane-spanning region, suggesting that the Flo1 protein is an integral membrane protein and a cell wall component. PMID- 8203163 TI - The sequence and potential regulatory elements of the HEM2 promoter of Saccharomyces cerevisiae. AB - This paper reports the 1890-bp sequence located upstream of the HEM2 gene of Saccharomyces cerevisiae. The following potential regulatory protein-binding motifs were found: ABF1-binding site, yAP1-binding site, two REB1-binding sites, a cyclic AMP-responsive element, RAP1-binding site, and several HAP2-HAP3-HAP4 binding sites, implicating a complex regulatory mechanism governing expression for the HEM2 gene. PMID- 8203164 TI - The complete sequence of an 18,002 bp segment of Saccharomyces cerevisiae chromosome XI contains the HBS1, MRP-L20 and PRP16 genes, and six new open reading frames. AB - We report the sequence of an 18,002 bp DNA fragment from the right arm of Saccharomyces cerevisiae chromosome XI. This segment contains nine complete open reading frames (ORFs), YKR401 to YKR409, and part of another ORF, YKR400, covering altogether 87.2% of the entire sequence. One of them, YKR400, encodes an NAD-dependent 5,10-methylene-tetrahydrofolate dehydrogenase. YKR404, YKR405 and YKR406 correspond to the previously characterized HBS1, MRP-L20 and PRP16 genes, coding for a translation elongation factor, a mitochondrial ribosomal protein and an ATP-binding protein, respectively. The putative product of YKR407 contains the zinc-binding region signature of neutral zinc metallopeptidases. The five other ORFs do not show significant homology to any known protein. PMID- 8203165 TI - Sequence analysis of a 10 kb fragment of yeast chromosome XI identifies the SMY1 locus and reveals sequences related to a pre-mRNA splicing factor and vacuolar ATPase subunit C plus a number of unidentified open reading frames. AB - We report the DNA sequence analysis of a region on the left arm of chromosome XI of Saccharomyces cerevisiae extending over 10 kb. The region contains five open reading frames (ORFs) of greater than 100 amino acids which do not show significant overlap with other ORFs. YKL408 contains a sequence with strong similarity to the RNA helicase pre-mRNA splicing factors PRP2, PRP16 and PRP22 (Burgess et al., 1990; Company et al., 1991; Ruby et al., 1991). YKL409 corresponds to the gene SMY1, the sequence of which was previously reported by Lillie and Brown (1992). YKL410 is identical to ATPase subunit C (Beltran et al., 1992) except for an N-terminal extension. YKL406 and YKL407 show no significant identity with any sequences in the databases searched. PMID- 8203166 TI - Sequence analysis of a 3.5 Kb EcoRI fragment from the left arm of Saccharomyces cerevisiae chromosome XI reveals the location of the MBR1 gene and a sequence related to a GTPase-activating protein. AB - We present the DNA sequence analysis of a region covering a 3.5 kb EcoRI fragment from the left arm of chromosome XI from Saccharomyces cerevisiae. This region contains five open reading frames (ORFs) which code for proteins of greater than 100 amino acids. ORF YKL425 codes for the previously sequenced Mbr1 (Valens et al., 1991; Daignan-Fornier et al., 1993) which participates in mitochondrial biogenesis. YKL424 has identity with a GTPase-activating protein of higher eukaryotes. The three remaining ORFs have no identity to known proteins within the databases screened and are not assigned ORF numbers as they are completely contained with ORFs YKL424 and YKL425. PMID- 8203167 TI - SED6 is identical to ERG6, and encodes a putative methyltransferase required for ergosterol synthesis. AB - Luminal endoplasmic reticulum (ER) proteins carry a sorting signal that allows them to be retrieved from the Golgi apparatus by a specific receptor. In yeast, this receptor is encoded by the ERD2 gene. Although retrieval of ER proteins does not appear to be an essential process, cells lacking ERD2 do not grow. Several multicopy suppressors of this growth defect have been isolated. The sequence of one of these, SED6, is presented here. Its product contains motifs characteristic of methyltransferases, and it is identical to ERG6, the presumed structural gene for S-adenosylmethionine:delta 24-sterol-C-methyltransferase. The gene is located adjacent to PDR4, near the centromere of chromosome XIII. PMID- 8203169 TI - Current awareness on yeast. PMID- 8203168 TI - Corrected sequence for the right telomere of Saccharomyces cerevisiae chromosome III. AB - A comparison of the sequences of telomere regions from several yeast chromosomes revealed an apparent cloning artifact for the right end of chromosome III. An integrating vector containing G1-3T telomere sequences was used to clone the right end of chromosome III from a strain related to S288C. The sequence of this clone confirmed that the published sequence was incorrect and demonstrated that the right telomere region of chromosome III is similar to other telomeres. PMID- 8203170 TI - [Preperitoneal implantation of Dacron mesh for treatment of recurrent inguinal hernia and bilateral inguinal hernia]. AB - The preperitoneal approach with implantation of a dacron sheet was applied in 37 patients with recurrent hernias and in 30 patients with primary bilateral hernias. In total 120 hernias were repaired. The patients were controlled prospectively for serious complications. The patients were examined every 3 months in the first and every 6 months in the second year after operation. The mean follow-up time was 17.2 months. COMPLICATIONS: In one patient with a combined hernia an indirect hernia sac was not detected intraoperatively, so it persisted. Recurrences were not observed. COMPLICATIONS (hematoma, fluid collections, wound infections, intraabdominal adhesions) occurred in 13.2 of the patients. CONCLUSIONS: The preperitoneal implantation of a dacron sheet is a safe and reliable procedure for treatment of recurrent groin hernias and primary hernias with a high risk of recurrence. The rate of infection is low under preventing measures. PMID- 8203171 TI - [Transperitoneal technique of preperitoneal mesh implantation in laparoscopic hernioplasty of direct and indirect inguinal hernias]. AB - The method of transperitoneal application of a large polypropylene-mesh in the preperitoneal space for laparoscopic inguinal hernia repair is described. The own experiences with a total number of 64 inguinal hernias are presented. The technique takes the principle of conventional hernia repair into account and appears to be a safe and effective way to repair indirect and direct inguinal uni or bilateral hernias. During a mean follow-up of 24 weeks one recurrence occurred resulting from an inadequate application of the mesh. The technique presented is effective for laparoscopic inguinal hernia repair with low morbidity. Long-term follow-up is needed to determine late recurrence rate. PMID- 8203172 TI - [Surgical therapy of cancer of the cervical esophagus]. AB - Esophagectomy and reconstruction of the esophagus is the treatment of choice in carcinoma of the cervical esophagus. Although the type of resection is almost standardized, the methods of esophageal reconstruction, replacement by a gastric tube, a free intestinal or colonic graft are discussed controversial. Adjuvant radiation or chemotherapy did not improve long-term survival. Our experience with 19 patients is reported and discussed with other european results. PMID- 8203173 TI - [Results of treatment of esophageal cancer]. AB - From 1.10.1972 until 1.1.1993 176 patients underwent esophageal resection for cancer of the esophagus. There were 72.7% squamous cell carcinomas and 24.4% adenocarcinomas. pTNM staging was as follows: Stage I: 7.3%; stage IIa: 33.5%; stage IIb: 11.9% and stage III 47.1%. The resection was performed in 92.6% by an abdominothoracic approach. Reconstruction was usually performed by transposition of the stomach. Only in 8 patients colon was used for esophageal replacement. The complication rate was 34.6%, mainly pulmonary complications were seen. The rate of anastomotic insufficiency was 6.2%. Hospital mortality was 15.3%, but decreased from 29.1% in the years 1972-1982 to 10.1% in the last decade. There was a significant correlation between the 5-year-survival-rate and the tumor staging respectively the lymph node involvement. The long-term results showed a relatively high percentage of reflux complaints and persistent dysphagia. But the general condition and quality of life were considered subjectively by 53.5% as good and by 42.8% as moderate. From these results it can be concluded, that surgery today offers the best chances for potential cure and a high quality of life. PMID- 8203174 TI - [Experiences with reliability and rate of complications in collar or thoracic anastomosis after subtotal esophagectomy]. AB - In the period from 1988-1992 we performed 148 subtotal esophagectomies. In 69% (102 cases) the operation was carried out because of squamous cell carcinomas of the esophagus, in 27% (40 cases) because of adenocarcinomas and in 4% (6 cases) because of other indications. In 97% (143 cases) the passage was reconstructed by means of a tubulized gastric pull-up established by Akiyama and in of a tubulized gastric pull-up established by Akiyama and in 3% (5 cases) by means of a colon interposition, whereby all interponates were pulled up through the posterior mediastinum. The esophago-gastrointestinal anastomosis was performed in 98% (145 cases) by a hand made suture end-to-side. In 2% (3 cases) we performed the anastomosis by a mechanical EEA device. The collar anastomoses (n = 88) on the posterior wall were covered with the remainder of the gastric fundus, the thoracal anastomoses (n = 60) on the anterior wall were secured by means of a plication. Postoperative surgical complications occurred in 22.7% of the collar and in 25.0% of the thoracal anastomoses. Insufficiencies (n = 3) were observed with thoracic anastomoses only 2 of the 3 insufficiencies were lethal. Postoperative paralysis of the n. recurrens, disturbance of swallowing coordination and aspiration occurred in 29.5% of the collar and in 13.4% of the thoracal anastomoses. In contrast to other reports we were able to show that the collar esophago-enteroanastomosis after subtotal esophagectomy is safer than the thoracic anastomoses with regard to anastomotic insufficiencies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203175 TI - [Effect of site and width of stomach tube after esophageal resection on gastric emptying]. AB - The gastric emptying of a mixed solid-liquid meal labeled with 99 mTc was evaluated in 14 healthy volunteers and in 14 subjects after esophageal replacement. The stomach had been placed seven times in the posterior mediastinum and seven times behind the sternum. The rate of emptying was measured by an anterior gamma-camera technique. Furthermore, the width of the esophageal substitutes was determined by CT-scans. The intrathoracic stomach displayed a prolonged emptying rate, independent of its location in the anterior or posterior mediastinum. Interestingly the width of the stomach influenced the discharge of the test-meal, whereby the more narrow the substitute the faster the emptying rate. PMID- 8203176 TI - [Late complications after prosthetic aortic replacement]. AB - Late complications following aortic graft replacement are rare. Within 5 years these severe complications have to be expected in about 1-3%. A staged but adequate treatment is necessary. If the renal arteries are included besides technical and anesthesiological experiences a refinement of vascular surgical technique is required. Nevertheless a high morbidity and mortality rate remains, depending on the expertise of the vascular surgeon, on an early and precise diagnosis as well as on the severity of additional organ diseases. Routine yearly ultrasound examinations following aortic graft replacement are recommended, to detect late complications before the events of rupture, graft enteric fistula or severe bleeding complications require extensive surgical procedures. Any vascular surgeon performing abdominal and thoracoabdominal aortic surgery has to be familiar with the basic diagnostic and therapeutic approaches managing late complications following aortic graft replacement. PMID- 8203177 TI - [Microbial translocation from the gastrointestinal tract--pathophysiologic phenomenon or catalyst for multiple organ failure?]. AB - The constant passage of intestinal microorganisms and endotoxin into the gut associated immune system is an important physiological process for its optimal function. Under the conditions of disturbed microflora homeostasis, impaired mucosal permeability, and immunocompromisation, translocation is pathologically increased both in the animal experiment and in man. The clinical relevance of increased translocation is not yet definitively established. But from lots of evidence it seems that in the immunocompromised critically ill with systemic inflammatory response syndrome/sepsis, microbial translocation plays an important role for the eventual outcome towards multiple-organ-failure. Our therapeutic efforts have to concentrate on protection of the gut mucosa by maintaining adequate splanchnic blood flow and providing early enteral nutrition. PMID- 8203178 TI - [Microfilters within the scope of infusion therapy--possibilities and problems in retention of microbial and particle contaminants]. AB - Contamination of parenterally applied fluids by bacterial and particulate material may contribute to the development of sepsis, multiple organ failure, and adult respiratory distress syndrome. 0.2 microns in-line filters are effective in reducing bacteria and foreign matter in the infused fluids. The rate of thrombophlebitis was demonstrated to be significantly reduced by in-line filtration. However, to date there is no definite evidence from clinical studies that these filters are effective in reducing overall morbidity and mortality. Furthermore the use of in-line filters reduces waste material and required nursing time, because the infusion systems have to be replaced every 96 hours as opposed to 24 hours without filters. In conclusion, use of 0.2 microns in-line filters in infusion therapy is cost effective and may enhance patients' safety. PMID- 8203179 TI - [Formation of a blind loop: an unusual bleeding site in chronic intestinal hemorrhage]. AB - The blind-pouch-syndrome may display a variety of symptoms. But it rarely causes intestinal bleeding. In a patient suffering from anemia of chronic intestinal hemorrhage, a blind-pouch was diagnosed through the search for colon polyps. A hemicolectomy with a side-to-side ileocolic anastomosis was performed 30 years ago, but there were no symptoms of maldigestion or malabsorption. The explorative laparotomy revealed an anastomotic stricture with a lot of coproliths in the ileum-blind-pouch. The histological examination of the resected anastomosis showed an unspecific inflammation of the mucosa. Excluding other potential causes of intestinal hemorrhage, this mucosal irritation was presumed to be the bleeding site. PMID- 8203181 TI - [The effect of different lactic acid isomers in the colon of rats]. AB - Depending on quantity and/or quality, the presence of lactic acid in the colonic lumen may be associated with metabolic damage of the colon. The influence exerted on the rat colon by the different isomers and racemic of the lactic acid, used at two extreme dilutions (20 and 100 mEq/l), has been the subject of study in this paper. The modifications on pH, water and electrolytes are associated with the absorptive/secretory action of the colonic wall. In addition, a study has been made on the influence of lactic acid on the colonic mucus and albumin permeation. Histopathologic studies of the caecum and left colon have been performed. There is a different colonic wall behaviour for each of the different isomers of the lactic and its racemic; a larger absorption of water, Na+ and Cl- for the D (-) isomer at a low concentration; its behaviour is completely opposite at high concentration. The final pH is higher when the D (-) isomer takes part; comparing the different isomers, there are small variations as far as albumin permeation is concerned. At high concentration there is a decline in Cl- absorption. The high percentage of erosions that take place especially in the caecum, where L (+) isomer can be found at high concentration, it is remarkable. The present observations suggest that the presence of lactic acid in (the) ulcerative colitis deserves great attention, especially in about the quantity and quality in which the acid can be found. PMID- 8203182 TI - [Characterization of antigenic types of circulating rotaviruses in Mendoza, Argentina based on typing of the external VP7 capsid protein]. AB - Rotavirus is one of the most common etiologic agents of acute diarrhea in childhood. Understanding the immunologic mechanisms involved in rotavirus diseases, including knowledge on seasonal and geographic antigenic variations may be crucial for vaccine development. A monoclonal antibody based ELISA specific for antigenic domains on the outer capsid protein VP7 has been developed and used widely in the past years. We studied the rotavirus VP7-serotype epidemiology causing diarrhea in children who consulted at two main hospitals of Mendoza, Argentina over a 20 month period. A total of 227 cases of diarrhea were identified, 45 of which (20%) were rotavirus positive. We're able to serotype 43 viruses (96%), 42 VP7-type 1 and one VP7-type 3. The VP7-type 3 was detected towards the end of the second year, possibly representing a new incoming VP7 type. Three electropherotype patterns were identified, two corresponding to VP7 type epidemiology in Mendoza, Argentina seems to be characterized by a relatively homogeneous pattern of circulation with a strong predominance of VP7-type 1 viruses, at least during the 20 month period studied, in contrast to what has been reported in larger, more cosmopolitan cities like Buenos Aires. PMID- 8203183 TI - [Isosorbide-5-mononitrate in the prevention of digestive hemorrhage in cirrhosis: randomized study]. AB - Isosorbide 5-mononitrate (5MI) is a preferential venous dilator that has been shown to decrease portal pressure in acute and long-term haemodynamic studies, and this is not associated with adverse effects on hepatic perfusion. The aim of this trial was to investigate the efficacy and safety of 5MI in the prevention of upper gastrointestinal bleeding in cirrhotic patients. Forty two cirrhotic patients with F2 or F3 esophageal varices showing "red signs" and who had never bled were included and randomly y assigned to receive either 5MI (group I,n23) or placebo (group P,n19). Patients with hepatocarcinomas or complications potentially lethal in the short-term or who were being given drugs such as steroids or interferon were excluded. The end points of the study were bleeding and death. There were no significant differences between the groups in the basal clinical and laboratory data. The mean +/- SD follow-up time was 49 +/- 36 and 43 +/- 25 weeks in the groups I and P, respectively. The percentage of patients free of bleeding 61 weeks after inclusion in the study was 62.4% in the group I and 46.3% in the group P (NS). The percentage of patients surviving 85 weeks after inclusion in the study was 81.2% in the group I and 39.8% in the group P (NS). Treatment did not have to be stopped in any patient of both groups because of side effects. In conclusion, 5MI is a safe drug for the chronic management of portal hypertension, that showed a trend to reduce the risk of bleeding and death in cirrhosis with large esophageal varices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203184 TI - Radiologic and endoscopic studies of gastric ulcers associated with Candida infection. AB - The radiologic and endoscopic studies in 30 lesions of 30 gastric peptic ulcers associated with candida infection diagnosed histologically and the follow-up studies in 23 lesions of 23 patients over period of 6 months to 12 years were performed. 1. The ratio of male to female was 5:1, 43% were found over 7th decade and 33% with systemic diseases. 2. Although the ulcers showed no characteristic endoscopic and radiologic features, half of them were found in the upper part of the stomach (60%), measured more than 2.0 cm in diameter (54%), with UI-II in depth (54%), with unclear border (60%). 3. The curability of gastric ulcers was low with 30% cured in 6 months or more of follow-up period. 4. The continuity of candida infection, bleeding or perforation from the ulcer, candidemia or fatal accident were not encountered without antimycotic treatment. PMID- 8203186 TI - Latent distal renal tubular acidosis (dRTA) in primary biliary cirrhosis (PBC) and chronic autoimmune hepatitis (CAH). AB - In an attempt to evaluate the latent distal renal tubular acidosis (dRTA7) in patients with primary biliary cirrhosis (PBC), and chronic autoimmune hepatitis (CAH), and differences between them in relation to the sodium urinary excretion ([Na]u), thirty four patients divided in two groups were studied. Group A: 17 patients who fulfilled criteria for PBC diagnosis (clinical and humoral evidence antimitochondrial antibody titles of 1/80 or above by indirect immunofluorescence technique, and liver biopsy). Group B: 17 patients who fulfilled criteria for CAH diagnosis (clinical and humoral evidence, antinuclear and smooth muscle antibody titles of 1/80 or above and liver biopsy). Patients with ascitis and/or edema were excluded from the study. Ability to acidify urine was evaluated by gradient between pC02 in urine and blood (U-BpC02) after alkali infusion. Five patients in Group A (29.4%7) and six in Group B(35.2%) had dRTA, (p = 0.49). When analyzing patients with dRTA in both groups, the mean [Na]u in Group A was 152.2 +/- 33.8, versus 50.8 +/- 8.1 mEq/l, in Group B. (p = 0.00016). We concluded that the prevalence of dRTA was similar in patients with PBC and CAH but the urinary acidifications impairment of the former did not correlate with [Na]u, as it did with the latter. PMID- 8203185 TI - [Endoscopic papillotomy and extraction of bile duct calculi in patients with gallbladder in situ and cholelithiasis]. AB - Cholecystectomy with surgical papillotomy is a prolonged procedure with significant morbidity and mortality. In patient stay is usually extended. Occasionally the bad general conditions and the advanced age of the patients contraindicate surgical procedures. Eventually, the drainage of the biliary ducts is inevitable. For this reason, since 1983, we are performing the endoscopic papillotomy and extraction of stones from the bile duct in patients with choledocholithiasis and cholelithiasis. Cholecystectomy was performed only in cases with real necessity. Ninety one patients, 26 men and 65 women, between 25 and 82 years, have been submitted to this procedure in our department. Cholecystectomy was performed in 52 cases after 24 to 72 hours post-papillotomy. Due to acute cholecystitis 12 patients had to be operated after a period of 2 months to 2 years. No cholecystectomy was performed in 27 patients, they are still asymptomatic. Then were no mortality related to the method. PMID- 8203187 TI - [Chronic idiopathic intestinal pseudo-obstruction: visceral myopathy. Report of 4 cases]. AB - Chronic intestinal pseudo-obstruction is the term applied to a heterogeneous group of functional motility disorders sharing a common clinical expression: signs and symptoms of bowel obstruction in absence of mechanical occlusion. It is caused by ineffective intestinal propulsion. The chronic form of intestinal pseudo-obstruction may be primary or secondary. Primary pseudo-obstruction or chronic idiopathic pseudo-obstruction (CIIP) defines a group of propulsive disorders having no recognized underlying diseases. This study presents four female patients, aged between 4 months to 7 years, and makes a review of the literature. The symptoms, very similar in three of them, were bilious vomiting, abdominal distention and constipation, alternating with diarrhea and malnutrition. The fourth patient, different from the others in the age of onset and evolution, only had severe constipation and abdominal bloating. The diagnostic was made by full thickness biopsies during laparotomy, getting specimens by mapping, at different heights of intestine and stomach. Samples were studied by optic and electronic microscopy and visceral myopathies were found. None of them had urinary disorders. Medical treatment consisted of total parental nutrition and/or enteral nutrition. Cisapride was not effective in the two patients who received it. PMID- 8203188 TI - Asthma and reflux. Coincidence or consequence? PMID- 8203189 TI - [Non-surgical treatment of biliary calculi]. PMID- 8203190 TI - Comparison of body sway analysis techniques. Assessment with subjects standing on a stable surface. AB - Different analysis methods for the objective measurements of body sway were examined to establish the most sensitive method for identifying changes in stability. Changes between stability with eyes open and eyes closed were used to assess the techniques. Body sway was measured in a group of normal subjects standing on a stable surface using "sway magnetometry," which measures hip movement in the sagittal and coronal planes by magnetic field detectors worn at the waist. The following analysis methods were studied; path length, mean distance from the centre, the area enclosed by the path of movement, and the areas of a convex hull, an ellipse and a circle enclosing the sampled points. The results showed that the path length technique had the smallest inter-subject variability, both with eyes open and eyes closed, and was the only technique whose mean Romberg Coefficient (Eyes Open/Eyes Closed) was more than two standard derivations from 1.0 (0.74 +/- 0.11, mean +/- S.D.), indicating that this technique showed greatest sensitivity for detecting changes in body sway. PMID- 8203191 TI - Effects of olivocochlear bundle section on otoacoustic emissions in humans: efferent effects in comparison with control subjects. AB - The effects of contralateral acoustic stimulation on evoked otoacoustic emissions (OAE) were examined in three subject groups in order that the impact of efferent olivocochlear bundle section (as a consequence of vestibular neurectomy) could be compared with normal findings, and with a control surgical population. Results demonstrated that the inhibitory effect of contralateral noise on OAE amplitude was absent from the cochlea with severed efferent fibers. These findings appear to be independent of acoustic reflex activity, as suppression was absent despite normal reflexes. Inter-aural suppression of emissions recorded from the patients' intact cochleae act as a control and show a clear reduction in amplitude during contralateral stimulation in a frequency specific pattern consistent with normal findings. Patients who had undergone a similar surgical approach for vascular decompression of the VIIIth nerve without vestibular nerve section, were studied in order to assess the impact of retrolabyrinthine surgery on inter-aural suppression. Inhibition of OAE amplitude was maintained in all control cases in both the operated and intact sides, and was consistent with suppression observed in normal subjects, suggesting that the surgical procedures had not disturbed inter-aural suppression of otoacoustic emissions. It is concluded that the olivocochlear efferent system, when activated by low level contralateral acoustic stimulation, has an inhibitory role in controlling the cellular mechanisms responsible for the generation of otoacoustic emissions in humans. OAE techniques in conjunction with contralateral acoustic stimulation may thus prove to be of value in providing a rapid and non-invasive clinical test of efferent function and offer a means of investigating the functional significance of the efferent auditory system in humans. PMID- 8203192 TI - Effect of experimental acidosis on nystagmus in rabbits. AB - Vertigo related to acidosis in Meniere's disease has been reported. This study was undertaken to ascertain whether acidosis has any effect on vertigo. Since patients with Meniere's disease usually show unilateral vestibular dysfunction, unilateral intratympanic injection of streptomycin sulfate (SM) was used to induce unilateral vestibular dysfunction in rabbits. Intratympanic SM injections induced vestibular destruction and elicited severe spontaneous nystagmus and ataxia. Then symptoms of acute vestibular upset gradually subsided and eventually disappeared completely. Three weeks after SM injections, in compensated rabbits, NH4Cl injection or CO2 inhalation was used to induce acidosis. Intravenous NH4Cl injection or CO2 inhalation induced nystagmus and ataxia again. In normal rabbits, no nystagmus was induced by NH4Cl injection or by CO2 inhalation. These results suggest that acidosis might be a cause of recurrence of vertigo in patients with unilateral vestibular dysfunction. PMID- 8203193 TI - Effects of electrical brainstem stimulation on tinnitus. AB - The primary aim of the auditory brainstem implant (ABI), an investigational device, is to restore auditory sensations in neurofibromatosis-2 patients deafened by bilateral acoustic neuroma surgery. An electrode is placed on the dorsal cochlear nucleus after the tumor is removed through the translabyrinthine approach. This procedure was performed on 18 patients: 13 were completely deafferentated after bilateral tumor removal and had received the ABI during surgery on the second-sided tumor; 5 were implanted at first-sided tumor removal. Three of these 5 patients had usable hearing remaining on the side of the second acoustic neuroma and were stimulated only during laboratory sessions. All patients had tinnitus. We used a questionnaire to assess the effects of brainstem stimulation on this symptom. Of the 18 patients, one early patient deceased, and one patient with no follow-up was not included in this study. Six patients who were unable to use the ABI because of temporary hardware problems or side effects from electrical stimulation were also excluded. Thus, we studied 10 patients. Of 7 patients who used their implant daily, 6 reported noticeable tinnitus reduction; the ABI had no effect in the remaining case. Of 3 recently implanted patients who used this implant only during laboratory testing, one patient reported complete suppression of tinnitus, one described worse tinnitus, and one reported no effect. PMID- 8203194 TI - Stapedius reflex and EABR thresholds in experienced users of the Nucleus cochlear implant. AB - Evoked auditory brainstem responses (EABR) and stapedius reflex thresholds were established in 7 experienced users of the Nucleus cochlear implant. Even using biphasic 400 microseconds/phase clicks for the EABR, responses were observed in only 5 patients; no stapedius reflex (SR) was seen in 3 patients, 2 of whom had a history of middle-ear disorder. The EABR threshold varied widely between subjective threshold and uncomfortable loudness level (ULL) for the same stimulus. The average SR threshold was found somewhat more consistently at 66% of the dynamic range between threshold and ULL, but grossly overestimated the most comfortable level (MCL) in most cases. To obtain equal loudness at the same current level we suggest that broad clicks (300 microseconds/phase) be used for EABR measurements, thus compensating for the lower repetition rate of EABR stimulus compared with the device fitting stimulus. PMID- 8203195 TI - Single channel recordings of calcium currents in chick cochlear hair cells. AB - Single Ca2+ channel currents were recorded from chick cochlear hair cells by using cell-attached patches. The elementary current was about -2 pA at 70 mV positive to the resting potential (R.P.+ 70 mV); the slope conductance over a 40 mV voltage range was 24 pS. The open time histogram was reasonably well expressed by a single exponential function, while the closed time histogram was expressed by a sum of two exponential functions. The Ca2+ channel was activated around R.P.+ 60 mV and the average ensemble current did not decay during 130 ms depolarization, suggesting that the Ca2+ channel in chick cochlear hair cells is the L-type. The Ca2+ channel has three modes of gating behaviour, expressed as current records with brief openings (mode I), no openings (mode 0), or long lasting openings and very brief closings (mode 2). PMID- 8203196 TI - Cytoskeletal organization of the vestibular supporting cells. Saponin perfusion method for observing intracellular structures by scanning electron microscopy. AB - The cytoskeletal organization of the guinea pig vestibular supporting cells was investigated employing the saponin perfusion method using scanning electron microscopy. The skeletal framework of a cell was composed of actin, intermediate filaments and microtubules. The membrane bound organelles such as nucleus mitochondria, endoplasmic reticulum, Golgi apparatus, etc. were also well documented. This made it possible to investigate the three-dimensional organization of cytoskeletons as well as their complex interaction with various membrane bound organelles. The intermediate filaments were usually seen surrounding the nucleus and extending through the cytoplasm which connected the nuclear membrane to the plasma membrane, reticular lamina or other cytoorganelles. The intermediate filaments also closely related to the desmosomes. These findings suggest that the intermediate filaments provide mechanical support to the cell and its nucleus. The microtubules were closely related to the secretory granules, Golgi apparatus and intermediate filaments, which supports the idea that the microtubules may control the distribution of intermediate filaments, and also play an important role for the transport of the secretory granules. PMID- 8203197 TI - Possible involvement of capsaicin-sensitive sensory nerves in the regulation of cochlear blood flow in the guinea pig. AB - Capsaicin-induced microcirculatory changes in the cochlea of anaesthetized guinea pigs were examined by laser-Doppler flowmetry. Close intraarterial capsaicin infusion into the anterior inferior cerebral artery at doses of 10-50 pmol/min was followed by dose-dependent vasodilatation. Capsaicin infused in a dose of 150 200 pmol/min or above resulted in vasoconstriction in the region examined. Topical capsaicin administration into the cochlea (50-150 pmol) resulted in very moderate vasodilation with a latency of 1-2 min. Perivascular capsaicin application onto the anterior inferior cerebellar artery elicited an elevated blood flow in the cochlea, too. It is concluded that the release of vasoactive substances from capsaicin-sensitive nerve fibres in the inner ear of the guinea pig may play a role in the control of the local microcirculation. These nerves may also be involved in the neurogenic inflammatory processes in the region. PMID- 8203198 TI - Involvement of Na(+)-H+ exchange in intracellular pH recovery from acid load in the stria vascularis of the guinea-pig cochlea. AB - The effect of acid load by NH4+ prepulse method on intracellular pH (pHi) and Na concentration ([Na+]i) in the stria vascularis tissue was studied using fluorescence ratio image microscopy. The pHi and [Na+]i were determined with fluorescence indicator dyes, 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein and sodium-binding benzofuran isophthalate, respectively. Intracellular acidification from the basal pHi of 7.12 +/- 0.08 to 6.82 +/- 0.08 was induced by NH4+ prepulse. Subsequent addition to the standard NaCl solution gradually increased pHi to the control value. This Na(+)-induced pHi recovery was significantly inhibited by the presence of amiloride and absence of external Na+. Basal free [Na+]i was 19 +/- 5 mM in the stria vascularis. In the same maneuver of acid load, the pHi recovery was associated with the increase in [Na+]i sensitive to the amiloride derivative. Thus, the process of the pHi recovery from acid load was demonstrated to involve the Na(+)-H+ exchange in the stria vascularis. PMID- 8203199 TI - Immunolocalization of Na+, K(+)-ATPase, Ca(++)-ATPase, calcium-binding proteins, and carbonic anhydrase in the guinea pig inner ear. AB - The distribution of Na+, K(+)-ATPase, Ca(++)-ATPase, carbonic anhydrase, and calcium-binding proteins were investigated immunohistochemically in paraffin sections of guinea pig inner ears. Marginal cells of the stria vascularis, type II fibrocytes of the spiral ligament, and cells in supralimbal and suprastrial regions, were positive for Na+, K(+)-ATPase. Type I fibrocytes of the spiral ligament were positive for Ca(++)-ATPase, carbonic anhydrase, calmodulin and osteopontin. In the vestibular system, dark cells were positive for Na+, K(+) ATPase. However, these cells and subepithelial fibrocytes were negative for Ca(++)-ATPase, carbonic anhydrase, and the calcium-binding proteins. In the endolymphatic sac, epithelial cells in intermediate and distal portions were positive for Na+, K(+)-ATPase, but the reaction was less than that in the stria. The same endolymphatic sac cells that were positive for Na+, K(+)-ATPase were also positive for Ca(++)-ATPase and calcium-binding proteins, but negative for carbonic anhydrase. The presence of Ca(++)-ATPase and calcium-binding proteins in the type I fibrocytes of the spiral ligament suggests that these cells are involved in mediating Ca++ regulation. Lower levels of Na+, K(+)-ATPase and the co-existence of Ca(++)-ATPase and calcium-binding proteins in the epithelial cells of the endolymphatic sac indicate that these cells have a distinctive role in ion transport that is different from that of the cells of the stria vascularis and vestibular dark cells. PMID- 8203200 TI - Strial dysfunction in a melanocyte deficient mutant rat (Ws/Ws rat). AB - A homozygous mutant rat at the white spotting (Ws) locus showing a deficiency of melanocytes has recently been found (4, 5). The function and morphology of the inner ear of the Ws/Ws rat were examined by auditory brainstem response (ABR), endocochlear DC potential (EP), and electron microscopy. The mean ABR threshold of the Ws/Ws rat was significantly higher than that of the control +/+ rat. Most Ws/Ws rats showed no or very little EP. In electron microscopy, the stria vascularis of the Ws/Ws rat proved to be very thin and flat with poor interdigitation of marginal cells, and absence of intermediate cells. The organ of Corti appeared to be intact in both the +/+ rat and the Ws/Ws rat. These electrophysiological and morphological findings suggest that the Ws/Ws rat suffered from severe hearing loss caused by strial dysfunction. PMID- 8203201 TI - Prevention of recurrent acute otitis media in otitis-prone children by intermittent prophylaxis with penicillin. AB - The question whether penicillin V (pcV) given intermittently upon signs of upper respiratory tract infections (URTI) in otitis-prone children might prevent recurrent bouts of acute purulent otitis media (AOM) is addressed. As compared with continuous long-term antibiotic treatment as prophylaxis in otitis-prone children, intermittent administration would reduce the overall consumption of antibiotics. Seventy-six otitis-prone children less than 18 months of age were included in this double-blind, randomized, placebo-controlled multicentre study. Follow-up was from January till June. One hundred and twenty-three episodes of AOM occurred. The number of AOM episodes was reduced by 50% in the children on pcV during URTI episodes as compared with those on placebo. No obvious ecological drawbacks were noted. Thus, the described mode of pcV administration seems to be a rational and safe way to reduce the number of AOM episodes in otitis-prone children. PMID- 8203202 TI - Cellular localization of carnosinase in the human nasal mucosa. AB - The cellular localization of the enzyme carnosinase in human nasal mucosa was investigated using immunoperoxidase and double-staining immunoflourescence techniques. In the olfactory mucosa, carnosinase immunoreactivity was localized in the sustentacular cells, the acinar cells of Bowman's glands, and the perinuclear region of a small subset of olfactory receptor neurons. In the respiratory mucosa, carnosinase immunoreactivity was identified in the secretory vesicles of the epithelial goblet cells as well as in the respiratory glands. There was an age-related trend toward a decrease in the intensity of carnosinase immunoreactivity in the olfactory mucosae of older subjects. These results suggest that the role of carnosinase may be to provide the amino acids histidine and beta-alanine, the products of carnosine hydrolysis, to the amino acid pool for protein synthesis in the cells that secrete nasal mucus and in olfactory receptor neurons. PMID- 8203203 TI - Interleukin-5 gene expression in nasal mucosa and changes in amount of interleukin-5 in nasal lavage fluid after antigen challenge. AB - Eosinophils and their products are known to cause hyperreactivity and swelling of the nasal mucosa in subjects with nasal allergy. Interleukin-5 (IL-5) not only induces differentiation and proliferation of immature eosinophils but also causes mature cells to accumulate and activate. This study shows that IL-5 is actually produced in the human nasal mucosa by antigen challenge, and it further investigates the changes in the amount of IL-5 in nasal lavage fluids after antigen challenge. Expression of mRNA for IL-5 in nasal mucosa was investigated using the reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis. Among the 4 subjects with nasal allergy examined in this study, expression of mRNA for IL-5 was observed in 2 prior to antigen challenge; within 6 h after antigen challenge it was seen in 3 subjects. We also found that the amount of IL-5 in the nasal lavage fluids obtained consecutively after antigen challenge increased predominantly in the late phase, and that the number of eosinophils in the IL-5 positive group was significantly higher than that in the IL-5 negative group. These results strongly suggest that IL-5 contributes to the recruitment of eosinophils in the nasal mucosa of the subjects with nasal allergy. PMID- 8203204 TI - Lack of detection of human papillomavirus (HPV) in transformed laryngeal keratoses by in situ hybridization (ISH) technique. AB - Laryngeal keratosis (LK) is a precancerous mucosal change with a variable possibility of malignant transformation. Recent studies evidencing HPV-DNA genomes in a large series of non-malignant and malignant laryngeal lesions suggest a role of HPV in the transformation of laryngeal lesions possibly in synergistic interaction with other carcinogens. In this study, we analyzed 115 biopsy specimens from benign laryngeal lesions to evaluate the risk of malignant transformation and its relationship to degree of dysplasia and to histological features of virus cell infection. The rate of transformation of LK was 8% (9/115). Our results indicate that the risk of transformation in laryngeal keratoses without dysplasia (LKWOD) is lower than that in laryngeal keratoses with dysplasia (2.2% vs 25%, respectively) (p < 0.05). An increased risk of malignant evolution in laryngeal keratoses with dysplasia (LKWD) was also related to the degree of dysplasia (rate of transformation of 12.5, 22.2 and 36% in mild, moderate and severe dysplasia, respectively). Histological features suggesting HPV infection (koilocytic-like atypia and epithelial papillary hyperplasia) were found in 6 LK only, no case subsequently developing cancer. In both benign and transformed LK, analyzed by ISH, we failed to detect HPV genomes, suggesting a major role of others carcinogens, such as tobacco and/or alcohol, in the transformation of LK. PMID- 8203205 TI - Sex hormones in papillary carcinoma of thyroid gland and pleomorphic adenoma of parotid gland. AB - This is a histologic study using the peroxidase-antiperoxidase (PAP) method for demonstration of estradiol, testosterone, dihydrotestosterone and progesterone in the normal thyroid gland and papillary carcinoma of the thyroid gland as well as in the normal parotid gland and pleomorphic adenomas. The results show that the normal follicular epithelia of the thyroid gland and the intercalated, striated ducts in the parotid gland stained for sex hormones. Estradiol was positive in both thyroid and parotid gland tissue in females and males. In females, testosterone and dihydrotestosterone were not recognized in the thyroid gland tissue and were only weakly present or negative in parotid gland tissue. In males, both testosterone and dihydrotestosterone were positive. Papillary carcinoma of the thyroid gland and pleomorphic adenoma of the parotid gland were positive for estradiol but not for testosterone or dihydrotestosterone. This suggests that there is a sex difference in the influence of sex hormones on the normal thyroid and parotid glands, and that estradiol exerts an influence on papillary carcinoma of the thyroid gland and pleomorphic adenoma of the parotid gland. PMID- 8203206 TI - Absence of evidence for infection with the human spuma retrovirus in an outbreak of Meniere-like vertiginous illness in Wyoming, USA. PMID- 8203207 TI - Human spumaretrovirus in the etiology of sudden hearing loss. PMID- 8203208 TI - Recent activities in neurotology and otorhinolaryngology. Scientific papers dedicated to Professor Yoshio Koike on his retirement. PMID- 8203209 TI - Optokinetic nystagmus elicited by a random dot pattern and a wide interval stripe pattern in normal subjects. AB - In optokinetic stimulus in practical living conditions, not only the central fovea but also the peripheral retina are strongly stimulated. In order to investigate the influence of this stimulus on the peripheral retina in optokinetic nystagmus (OKN), we tested OKN elicited by a pattern of numerous random dots (ROKN) in 30 normal subjects and compared the results with those of OKN elicited by a wide interval stripe pattern. The most significant difference between the two response patterns was the correlation between slow phase velocity and slow and fast phase amplitude. In ROKN, the nystagmus amplitude was highly correlated with slow phase velocity. On the other hand, in SOKN there were two types of correlation between slow phase velocity and nystagmus amplitude. One indicated low correlation, which was extremely predominant, and the other, high correlation as in ROKN. This tendency was more marked in the fast phase amplitude. Although it is generally accepted that OKN fast phase in SOKN is controlled by voluntary saccade, our results indicate that ROKN is more strongly controlled by reflective resetting eye movements, which is similar to the nystagmus fast phase in vestibular nystagmus. PMID- 8203210 TI - Computer analysis for routine electronystagmography tests. AB - A computer program has been developed for on-line analysis of routine electronystagmography (ENG) tests. With this system, data acquisition of eye movements and stimulus signals obtained from ENG are accomplished at a rate of 200 Hz through a 12-bit analog-digital converter. A small spotlight for eye tracking tests is sinusoidally driven by a computer-generated analog signal. Six optokinetic stripes projected onto a screen are also controlled by the computer. Seven spots for saccade tests can be turned on or off based on digital signals produced through a digital output device. There are three types of eye movements in this series: nystagmus, pursuit eye movement and saccadic eye movement. An algorithm for the analysis of different eye movements is described in this paper. Recent significant advances in computer technology make it possible to perform such complicated tasks and to accomplish quantitative assessment of any type of eye movements in routine ENG tests. Consequently, computer analysis provides clues to the location of a disease and is very useful as a diagnostic tool in routine ENG testing. PMID- 8203211 TI - Rebound positional nystagmus as a peripheral origin. AB - Three cases of rebound positional nystagmus (RPN) are discussed in the present study. In all cases, spontaneous nystagmus was absent in the primary position, but positional nystagmus appeared in the side down position, and then nystagmus in the reversed direction appeared when the patient was returned to the primary position. The characteristics of RPN in the cases we studied were very similar to those of benign positional nystagmus. Tinnitus was accompanied with vertigo in Cases 2 and 3, and the glycerol tests were positive in Cases 1 and 3. There were no other abnormalities of ocular movements, neurological and neuroradiological examinations suggestive of central nervous system disorders indicating that RPN can be ascribed to peripheral lesions. A selective review of the literature is presented. PMID- 8203212 TI - Role of the prepositus hypoglossi nucleus on primary position upbeat nystagmus. AB - Electrolytical destruction of the floor of the fourth ventricle was performed on 10 cats in order to produce primary position upbeat nystagmus (PPUN). In 5 cats who had unilateral lesions of the floor of the fourth ventricle, PPUN was never seen. Two of the remaining 5 cats, who had bilateral lesions, showed PPUN. In 2 cats with PPUN, the oculomotor level of the caudal fourth ventricle, in order that PPUN may be developed, it is necessary that the prepositus hypoglossi nucleus (PH) be destroyed bilaterally. The present experiment suggests that bilateral PH lesions could result in a tonic imbalance for eye positions and eye movements of the vertical axis, resulting in a downward drift with a corrective saccade; PPUN. PMID- 8203213 TI - The effect of uvulonodular lesions on horizontal optokinetic nystagmus and optokinetic after-nystagmus in cats. AB - The effect of uvulonodular lesions on horizontal optokinetic nystagmus (OKN) and optokinetic after-nystagmus (OKAN) was investigated in alert cats. A lesion in each of 6 cats was made by suction-ablation under anesthesia. In the 3 cats with only a uvular lesion, both the initial slow phase velocity and the time constant of OKAN were unchanged. In the remaining 3 cats whose lesions included the nodulus as well as the uvula, the time constant of OKAN was markedly prolonged, but the initial slow phase velocity of OKAN was not affected. The postoperative average time constant of OKAN increased from the normal value of 9 s to about 40 s. In contrast, OKN parameters (the steady-state velocity and the rising time constant) were not affected by uvular or uvulonodular lesions. These results strongly suggest that the nodulus is involved in the velocity storage mechanism and might control the discharge characteristics of the velocity storage integrator. PMID- 8203214 TI - Effect of aging on smooth pursuit eye movement. AB - Examination of smooth pursuit eye movement is useful for detecting central nervous system disorders. It is important to take patient's age into consideration when evaluating smooth pursuit eye movement. The purpose of the present study was to clarify the effect of aging on smooth pursuit eye movement. Thirty healthy volunteers (three groups of 10 volunteers, in their fifties, sixties, and seventies and over, respectively) served as subjects, and 10 healthy young volunteers (23 to 33 years old: mean age 26) served as controls. The pursuit target was driven by sinusoidal waveform with various amplitudes and frequencies. Target peak velocities ranged from 12.6 to 94.2 degrees/s. Eye movement signals were recorded d.c. EOG and pursuit gain (ratio of eye peak velocity to target peak velocity) was measured by a computer. Pursuit gain decreased with increasing target frequency and velocity in all age groups. This tendency was more remarkable in the older groups than in the young controls; in particular, it was more frequently seen at a frequency of 0.5 Hz. On the other hand, there was no significant relationship between pursuit gain and the target amplitude. In the group in their seventies and over, pursuit gain was saturated at about 60 degrees/s. PMID- 8203215 TI - Detection of peripheral vestibular disorders by the pendular rotation test in cats. AB - Unilateral vestibular disorders were induced in 3 cats by means of the injection of a small amount of sodium hydroxide into the middle ear, and vestibulo-ocular responses (VOR) to various kinds of pendular stimulation were investigated at 1 week and at 1, 2, 3, 4, and 5 months after the operation. The pendular rotation test was performed at frequencies of 0.025, 0.1, 0.25 and 0.5 Hz, and peak velocities of 50, 100, 150, and 200 degrees/s, and the directional preponderance of the VOR gain (DP%) was measured using a computer. DP% 1 week after the operation was still very high at each frequency and velocity of the stimulation. On the other hand, DP% more than 1 month after the operation had decreased markedly, although it increased with an increase in the velocity of stimulation at all frequencies except at 0.5 Hz, and DP% at a velocity of 200 degrees/s was still high even 5 months later. This suggests that high velocity pendular stimulation should be used to detect unilateral vestibular disorders. PMID- 8203216 TI - Ocular abnormalities in amyotrophic lateral sclerosis. AB - It has long been known that the oculomotor system is not involved in amyotrophic lateral sclerosis (ALS). In early stages. Some authors suggest oculomotor abnormalities in some patients. In the present study, quantitative analysis of ocular movements including smooth pursuit eye movements, optokinetic nystagmus (OKN), visual suppression of vestibular nystagmus (VS), and horizontal saccades were investigated in 9 patients with ALS. These patients were neurologically diagnosed as having ALS in the early stage. The results were as follows: The velocity of saccade was markedly reduced in 4 patients. In addition, there were abnormalities of smooth pursuit (one patient), OKN (one patient) and visual suppression (2 patients). Furthermore, these abnormalities were observed more often in patients with bulbar signs. In conclusion, the results suggest a existence of ocular abnormalities in ALS, even at early stages. PMID- 8203217 TI - Quantitative analysis of oblique ocular movements. AB - In the present study, oblique saccadic eye movements in the orthogonal and oblique directions were investigated in 10 normal subjects, and a computer program was used to accomplish quantitative assessment of oblique eye movements. Eye movements were recorded with direct-current electronystagmography (DC-ENG) and a 12-bit analog to digital converter was used to collect analog data of horizontal and vertical eye position, and stimulus signals at a sampling rate of 200 Hz. The oblique eye movement was displayed two-dimentionally on a high resolution color graphic terminal for the evaluation of the trace of eye movements, and the peak velocity and the amplitude of the horizontal, vertical and oblique saccades were calculated. It was frequently found that the tracing line in the oblique saccadic eye movement was not completely straight, but loosely curved. The velocity of the vertical component of the oblique saccade was much lower than that of the horizontal component. This suggests that oblique saccades might be made by synchronized but independent vertical and horizontal pulse generators, and the system developed this time might be very useful for investigation of oblique eye movements in both the clinical and physiological field. PMID- 8203218 TI - Clinical advantages of electroneurography in patients with Bell's palsy within two weeks after onset. AB - One of the advantages of applying ENoG to patients with Bell's palsy resides in its quantitative determinability for the axons which do not undergo wallerian degeneration. The relation between the ENoG value each day after onset and during the recovery process was investigated in 551 patients with Bell's palsy within 2 weeks after onset in order to consider the diagnostic value of ENoG. It was discovered that ENoG on patients with Bell's palsy makes it possible to reveal the extent of wallerian degeneration by 7 days after the onset of palsy. Accordingly, treatment of Bell's palsy should be administered within the above 7 days; as early as 8 days after onset, exact prognostic diagnosis and judgment of therapeutic effect from ENoG values were concluded to be practicable. PMID- 8203219 TI - Effects of aging on amplitude-modulation following response. AB - Phase spectral analysis as developed by Fridman (1982) was used to detect amplitude-modulation following response (AMFR). The threshold of AMFR was determined with greater sensitivity and accuracy by phase spectral analysis than by visual analysis. Using this method, a modulation frequency (MF) of 80 Hz was found optimal for detecting AMFR in young children (ranging in age from 2 to 4 years) during sleep, for whom there is no advantage in recording 40-Hz steady state responses. To determine the optimal MF for detecting AMFR during sleep in children less than 2 years of age and age limitation for using 80-Hz MAFR in objective audiometry, AMFR as a function of MF was investigated during sleep in 25 children with normal hearing ranging from 4 months to 15 years of age, and 10 normal hearing adults. The stimulus was a 1000 Hz, 50 dBnHL sinusoidally amplitude modulated tone with a modulation depth of 95%. MF 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. Phase spectral analysis showed AMFR at MF of 80 Hz to be the most stable and reliable in all children during sleep among MFs from 20 to 200 Hz. Spectral amplitude analysis demonstrated 80-Hz AMFR to have a high S/N ratio in all children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203220 TI - Facial nerve palsy in children: clinical aspects of diagnosis and treatment. AB - Eighty-two children with facial palsy aged less than 6 years were examined. Sixty four cases, excluding patients with congenital and traumatic palsy, were distributed through the ages, but a predominant tendency to symptomatic palsy for cases aged less than 2 years was observed. Facial movement scoring was not practical in prognostic diagnosis in cases aged under 4 years, while ENoG was useful in all age-groups. Of 58 cases of acute peripheral facial palsy, 29 were observed clinically but given no treatment, 9 were given steroids, and 16 were given vitamins and other drugs. In the patients with acute peripheral facial palsy in whom a follow up study was performed, 56 cases (96.6%) showed complete recovery. The time of recovery was independent of treatment. Facial palsy in children is considered to have a good prognosis regardless of treatment. Steroid administration thus does not appear to be necessary in children with acute facial palsy. PMID- 8203221 TI - Recording of single fiber electromyography in patients with peripheral facial palsy. AB - We determined muscle fiber density with single fiber electromyography (SFEMG) to discuss the condition of re-innervation after the recovery of facial movement in cases of peripheral facial palsy. Muscle fiber density was then compared with electroneurography (ENoG) which is thought to correlate with the severity of facial neuropathy in the early stage after the onset. The degree of neuropathy and subsequent recovery of innervation was also discussed. The subjects were 36 patients with peripheral facial palsy (30 patients with Bell's palsy and 6 with Hunt's syndrome), treated at our hospital, in whom ENoG could be recorded within 2 weeks after the onset. Muscle fiber density was determined after the recovery of facial movement. As a control, muscle fiber density was determined in 11 normal adults, and muscles on the healthy side in 23 patients with Bell's palsy. Muscle fiber density was 1.44 +/- 0.15 (mean +/- S.D.) in normal adults and 1.51 +/- 0.18 on the healthy side in patients, showing no significant difference. Data on the affected side were divided into 4 groups according to the minimum ENoG level within 2 weeks after onset and were compared with the normal group. In all cases with an ENoG level of 40% or more, muscle fiber densities were normal, and no significant differences were noted between the affected side and the healthy side. In cases with an ENoG level of less than 40%, muscle fiber density increased significantly with increasing severity of denervation. These findings suggest that collateral sprouting is absent in cases of peripheral facial palsy who show an ENoG level of 40% or more, or no wallerian degeneration. PMID- 8203222 TI - Electrophysiological study on the pathology of synkinesis after facial nerve paralysis. AB - By conducting electrophysiological tests on patients with facial nerve paralysis, the characteristics of synkinesis and the mechanisms of its manifestations were examined. The subjects were 114 patients of facial nerve paralysis on whom electroneurography (ENoG) and the blink reflex were conducted. As a result, it was indicated that synkinesis could be determined by the blink reflex, and that the frequency of synkinesis manifestation increased with severity of paralysis. From examination during the latent period, early component (SI) recognized in the cases of synkinesis was found to be the waveform which passed the fibers with a slow conducting speed. It was not related to the degree of degeneration of nerves for either the severe or light degeneration of nerves. From the above result it was concluded that synkinesis is generated as a misdirection of reproduced nerves. PMID- 8203223 TI - Facial nerve enhancement in Gd-MRI in patients with Bell's palsy. AB - The diagnostic value of a contrast enhanced MRI in patients with Bell's palsy was investigated. It was a characteristic finding that the internal acoustic meatal segment of the facial nerve was enhanced only on the affected side. The signal intensity ratio of the geniculate ganglion and the tympanic segment was significantly higher on the affected side than on the normal side. The severity of the facial palsy and the results of physiological examinations showed no relation to the results of MRI scans. Gd enhanced MRI thus appears to provide some useful findings for estimating the affected region of Bell's palsy, whereas it is not considered to be valuable in the diagnosis of severity. PMID- 8203224 TI - Gd-DTPA enhanced MRI in Ramsay Hunt syndrome. AB - Ten patients with Ramsay Hunt syndrome underwent magnetic resonance (MR) scans. In many examinations, abnormal enhancement of the 7th nerve in the internal acoustic meatal segment through the mastoid segment was observed. Out of seven patients with cochlear and/or vestibular symptoms, only one showed abnormal enhancement of the 8th nerve, in addition to the 7th. The other 6 patients showed the same findings as in Bell's palsy, showing no enhancement of the 8th nerve. This suggests that clinical symptoms have no relation to the results of MRI. Enhanced MRI is the most sensitive means of making differential diagnoses between Hunt's syndrome and tumors, but it is impossible to detect all lesion sites corresponding to the symptoms in Hunt's syndrome. PMID- 8203225 TI - Deltopectral flap for one-stage reconstruction of pharyngocutaneous fistulae following total laryngectomy. AB - Postoperative pharyngocutaneous fistulae are troublesome complications after total laryngectomy. To manage this complication, we devised an operative method consisting of a one-stage repair using a deltopectal flap. With this technique we can immediately cover both skin and pharyngeal defects. We have applied this method to 5 patients all of whom have successfully recovered their swallowing function. PMID- 8203226 TI - Trapezius osteomyocutaneous flap in reconstructive surgery for mandibular and oral defects. AB - A scapular-trapezius osteomyocutaneous flap was used for mandibular reconstruction in 4 cases of oral cavity carcinoma after segmental resection of the mandible. In 3 cases, both the flap and bone took well, and the functional and morphological results were satisfactory. In one case, impaired venous return resulted in flap necrosis; a second reconstruction was performed using a rib latissimus dorsi osteomyocutaneous flap. Functional disturbances of the donor site were minimal and, because the donor site was on the back, the cosmetic result was excellent. This flap is a bone-attached compound flap using the transverse cervical artery and veins as the vascular bundle, and is thought to be useful in the reconstruction of mandibular defects associated with extensive tissue defects of the oral cavity. PMID- 8203227 TI - Results of treatment of laryngeal cancer. AB - Eighty-one laryngeal cancer patients treated at our clinic during the past ten years were studied clinically. The proportion of patients in their sixties was highest and the number of males was much larger than that of females, at a ratio of 15:1. Laryngeal cancer was classified as glottic, supraglottic, and subglottic in 58, 19, and 4 cases, respectively, and glottic cancer patients accounted for more than half of these. The cumulative 5-year survival rate in all patients was 79.6%, and the rates in glottic and supraglottic cancer patients were 82.2% and 83.3%, respectively. Cumulative 5-year survival rates in patients in Stages I, II, III and IV were 83.7%, 83.9%, 83.3%, and 55.5%, respectively. Recurrence after radiotherapy was controlled by salvage operations satisfactorily in Stages I and II, but the prognosis of recurrent cancer was poor for patients in Stages III and IV. A selective review is given. PMID- 8203228 TI - Cystic lymphangioma and plunging ranula treated by OK-432 therapy: a report of two cases. AB - Among head and neck angiotumors, cystic lymphangioma occurs in infancy in most cases and it is rare in adulthood. Plunging ranula is one of the diseases which need to be distinguished from lymphangioma, though operation is the first choice therapy for both of these. In the present study, we report on 2 cases in whom we conducted intralesional injection of OK-432 for cervical lymphangioma and ranula found in 20 and 35 year-old female patients. We obtained excellent improvement. First of all, we punctured the tumors and sucked out the liquid content as much as possible, and then used OK-432 in the same volumes to those drawn out. No swelling was observed in either patient after 1 month, and cysts disappeared in CT 4 and 12 months after injection, respectively; at present, the prognosis is satisfactory, without recurrence. The intralesional injection of OK-432 is considered an effective method, as the speed of complete disappearance by this therapy is high. Cosmetically it is superb, leaving no lesions in the skin of the injection site. PMID- 8203229 TI - A case of myeloma with facial palsy. AB - Myeloma in the left temporal region was seen in a 71-year-old male who also had facial palsy, hearing loss and tinnitus on the left. In this case, none of the laboratory test results had indicated myeloma. Diagnosis of myeloma in this case was made from findings of a CT scan of temporal bone and the results of biopsy of the external auditory canal lesion. In the CT scan, marked destruction of the bone was seen, extending from the mastoid air cell to the posterior wall of the external auditory canal. The biopsy of the mass lesion in the left auditory canal revealed proliferation of lymphoplasma-cytoid cells. This case is reported along with laboratory test findings, clinical findings, and a review of the literature. PMID- 8203230 TI - Diagnostic specificity of anti-neutrophil cytoplasmic antibodies (ANCA) in otorhinolaryngological diseases. AB - The incidence and titer of ANCA were examined with 871 sera from patients with otorhinolaryngological diseases at our hospital. The cytoplasmic pattern of ANCA (c-ANCA) whose titer was more than 16 was detected only in the sera of patients with Wegener's granulomatosis (WG). The incidence of c-ANCA in active WG was more than 90%. The perinuclear staining pattern of ANCA (p-ANCA) was detected in almost 40% of patients with Sjogren's syndrome, 2.0% of inflammatory diseases and 1.0% of tumorous diseases. A high diagnostic value of c-ANCA in WG was found in patients with otorhinolaryngological diseases. PMID- 8203231 TI - Effects of supernatant from tonsillar cell culture on neutrophil functions. AB - The palatine tonsil is the most important element of Waldeyer's ring as a defense mechanism against various microorganisms. The neutrophils are the initial active participants in bacterial infection and inflammation, but their interaction with other cellular participants is poorly understood. To clarify this point, the effects of culture supernatant from human tonsillar cells on the peripheral neutrophil function were investigated. Supernatants from tonsillar cells were incubated in the presence or absence of streptococcal preparation (OK-432) enhanced chemiluminescence, adherence, phagocytosis, chemotaxis, and superoxide production of human peripheral neutrophils. The results suggest that tonsils play an important role in the regulation of neutrophil function. PMID- 8203232 TI - Neutrophil activating activity of tonsillar cells from patients with tonsillitis. AB - The previous paper demonstrated that tonsillar cells cultured in vitro in the presence or absence of a streptococcal preparation, OK-432, produce factors that activate various neutrophil functions. In the present study, examination was made of the factor productivity of tonsillar cells from patients with chronic tonsillitis of varying severity, and palmoplantar pustulosis (PPP). Tonsillar cells from patients with severe tonsillitis and PPP incubated with culture medium alone produced a much greater amount of active factors compared with those from patients with mild tonsillitis. When tonsillar cells were incubated in the presence of OK-432, augmentation in factor production by the addition of OK-432 was less in former than latter cases, suggesting that factor production from tonsils correlates with the course of inflammation in this organ. PMID- 8203233 TI - Detection of anti-neutrophil cytoplasmic antibodies (ANCA) using the immunoperoxidase method. AB - Anti-neutrophil cytoplasmic antibodies (ANCA), which are present in Wegener's granulomatosis (WG) and other systemic vasculitis, were detected using the immunoperoxidase method rather than the indirect immunofluorescence method. It was possible to distinguish ANCA patterns (c-ANCA, p-ANCA) by the immunoperoxidase method. When neutrophil smears were treated with 0.4% hydrogen peroxide solution, the endogenous peroxidase activity was sufficiently inhibited. ANCA was also detected, using HL-60 cells (human promyelocytic leukemia) and THP 1 cells (human myelocytic leukemia) as substrates. PMID- 8203234 TI - Eosinophil and eosinophil cationic protein in allergic rhinitis. AB - To evaluate the roles of eosinophils in allergic rhinitis, eosinophil cationic protein (ECP) levels in sera and nasal secretions were measured in 28 patients with allergic rhinitis. In patients, blood eosinophil counts and serum ECP levels were significantly higher than in controls (p < 0.05). However, there was no statistically significant correlation between blood eosinophil count and serum ECP level (r = 0.025). The number of eosinophils and the ECP level in nasal secretion were also measured. In patients, the ECP level increased with the number of eosinophils, and the ECP level in nasal secretion was significantly higher than in controls (p < 0.05). These results suggest that eosinophils and ECP play important roles in allergic rhinitis. PMID- 8203235 TI - A study of fungal infections in otorhinolaryngology. AB - It is said that fungal infections in the area of otorhinolaryngology often occur in association with a decrease in the immune function and that indigenous fungi rarely exhibit pathogenicity in the infections. Among the patients examined at our department between October 1989 and March 1993, 67 fungal strains were detected in 45 cases. Treatment of diseases in the area of otorhinolaryngology should always recognize the presence of fungal infections. PMID- 8203236 TI - Modified method of submucosal turbinectomy: mucosal flap method. AB - Sixteen patients with nasal obstructions were treated by use of a new technique of submucosal turbinectomy (mucosal flap method) which can reduce a large volume of the turbinate without leaving any mucosal defect. Subjective nasal obstruction showed improvement in all of the cases at 1 month after operation, and objective nasal obstruction examined with rhinomanometry was improved in 13 out of 16 sides of the noses (8 cases). Mucosal flaps were made from the turbinate mucosa facing the common meatus. After excision of the turbinate bone with the mucosa, the bone stump and mucosal defect were covered with the newly repositioned mucosal flap. It is considered that this mucosal flap method can reduce a large volume of the turbinate without leaving any mucosal defect. PMID- 8203237 TI - Detectability of amplitude-modulation following response at different carrier frequencies. AB - To assess the detectability of amplitude-modulation following response (AMFR) elicited at different carrier (CFs) and modulation frequencies (MFs) during sleep, as well as the usefulness of AMFR in evoked response audiometry, AMFR was examined in 10 adults with normal hearing while sleeping. The stimulus was a 50 dBnHL sinusoidally amplitude-modulated (SAM) tone with a modulation depth of 95%. The MF of the stimulus tone was varied from 20 to 120 Hz in 20 Hz steps and CFs were 500, 1000, 2000 and 4000 Hz. An SAM tone with a CF of 20,000 Hz was used for stimulation in 5 subjects to confirm that the response did not contain any artifact. Response was determined by phase spectral analysis. The component synchrony measure of AMFRs at MF of 40 Hz (40-Hz AMFR) was high at lower CFs, but 40-Hz AMFRs at higher CFs were unreliable. The detectability of 80-Hz AMFR was high for all CFs. It was confirmed that the response waveform was not contaminated by any electromagnetic artifact. Eighty-Hz AMFR detected by phase spectral analysis should thus be useful for predicting frequency-specific hearing thresholds during sleep. PMID- 8203239 TI - An experimental study on the generator of amplitude-modulation following response. AB - To clarify the contribution of the auditory cortex and the inferior colliculus to amplitude-modulation following response (AMFR), lesion experiments were conducted on 8 cats. Bilateral auditory cortices of 2 cats were aspirated, and the right inferior colliculus of 3 cats, and the left inferior colliculus of another 3 cats were electrocoagulated to make lesions. Auditory brainstem response (ABR) evoked by clicks and AMFR elicited with 1000 Hz sinusoidally amplitude-modulated tones, at modulation frequencies (MF) of 20-200 Hz in 20-Hz steps, were examined before and after making lesions. Stimulus intensity was fixed at 90 dB SPL in both responses. AMFR was detected by phase spectral analysis using fast Fourier transformation. No change was observed in the phase spectral analysis of AMFR after bilateral cortical lesions. Remarkable changes were observed in AMFRs at MFs lower than 80 Hz and 200 Hz after lesions in the ipsilateral inferior colliculus and at all MFs after contralateral lesions of the inferior colliculus, while no such change was observed in ABR. The results suggest that the auditory cortex is not the source of AMFR, but that the inferior colliculus has great impact on the generation of AMFR at modulation frequencies of 20 to 200 Hz. PMID- 8203238 TI - Storage and utilization of images in otorhinolaryngology. AB - The amount of data in the field of otorhinolaryngology has rapidly increased, in proportion to the growing number of patients. Medical imaging has especially expanded and the percentage of image data in all information is also large. Because the space to preserve image films is increasing, it is very important to preserve them and make them easily available. Therefore, we have established a graphic filling system for storing endoscopic and radiographic images on VHS video tape and magnet-optical disk (MOD), using a personal computer. The MOD filing system is useful for storing a large amount of medical records. The user can simultaneously see the text data and the picture image on a display, and thus this system can be utilized as a database for both decision making and medical research. PMID- 8203240 TI - A study on the phase spectral analysis of middle latency response and 40-Hz event related potential in central nervous system disorders. AB - The synchrony measure method, or SM method, a phase spectral analysis described by Fridman in 1984 for ABR, was applied to 40-Hz event-related potential (40-Hz ERP), and was found to be a useful method for automatic detection in predicting hearing thresholds across the audiometric frequencies. Although 40-Hz ERP was claimed by Galambos to be the summation of middle latency responses (MLR), its origin is still controversial. Moreover, only a few articles have reported on the clinical use of 40-Hz ERP in patients with neurological disorders. We recorded ABRs, MLRs, and 40-Hz ERPs in 59 patients with central nervous system (CNS) disorders, and analyzed the relationship between central lesions and MLR or 40-Hz ERP using phase spectral analysis. Abnormal findings in 40-Hz ERP were observed in 43 (72.9%) out of 59 cases with CNS disorders, and most of the abnormal cases had disorders involving the midbrain or thalamic lesions, especially on the side contralateral to stimuli. The results suggest that phase spectral analysis of 40 Hz ERP is useful in the detection of CNS disorders. PMID- 8203241 TI - Hearing preservation and improvement of auditory brainstem response findings after acoustic neuroma surgery. AB - Among 9 patients with acoustic neuroma who underwent tumor removal by the middle cranial fossa approach during the past 5 years, 6 were selected for hearing preservation surgery which was successful in 5 cases (83.3%). For the prediction of success in hearing-preservation, factors related to hearing preservation, including preoperative findings of neurotological examination, were analyzed. Postoperative hearing threshold correlated significantly with wave V latency and I-V interpeak latency of preoperative auditory brainstem response (ABR) and the SP/AP ratio of preoperative electrocochleogram and postoperative facial palsy. The size of tumors and preoperative results of speech audiometry did not correlate with hearing results. Postoperative ABR findings were normalized within the observation period from 5 days to 10 months in 3 hearing-preserved patients. Possible mechanisms for improvement of ABR findings after the removal of acoustic neuroma are discussed. PMID- 8203242 TI - Postoperative changes in the contralateral auditory brainstem response after microvascular decompression in cases of trigeminal neuralgia. AB - Postoperative changes in auditory brainstem response (ABR) in 40 patients with trigeminal neuralgia (TN) who underwent microvascular decompression (MVD) were analyzed. A high proportion (60%) were found to have a decrease in the latency of wave V in the contralateral (unaffected) ABR in the postoperative period. In some cases, a decrease in the latency of wave V was found on the unaffected side postoperatively while an increase was found on the affected side. Furthermore, in one case it was found that an improvement of the shortened latency of wave V on the unaffected side occurred in parallel with a recovery of prolonged latency on the affected side. This indicates that the decrease in the latency of wave V on the unaffected side corresponds to some retrocochlear lesion produced by MVD on the affected side, and shortened latency is considered to be a result of damage to the efferent system of the auditory pathway. PMID- 8203243 TI - Three frequency component waveforms of auditory evoked brainstem response in spinocerebellar degeneration. AB - Under adequate stimulus intensities, the power spectra of normal auditory evoked brainstem responses (ABRs) are composed of three major components: 0-350 Hz, 350 700 Hz and 700-1200 Hz. By means of a digital filter using fast Fourier transform, three ABR waveforms consisting of each frequency component of the power spectrum were obtained. The significance of these three component waveforms in the analysis of ABR abnormality was estimated in 30 patients with spinocerebellar degeneration (SCD). In conventional wave latency analysis, 9 out of 30 patients (30%) had abnormal ABRs, the main abnormality being prolonged interpeak latencies of waves I-III, I-V and the disappearance of wave V. On the other hand, component waveforms were abnormal in 82.5% of the cases. These results suggest that analysis of ABRs by the use of component waveforms is useful for detecting abnormality in the brainstem auditory pathway in SCD patients. PMID- 8203244 TI - Phase spectral analysis of auditory brainstem response in cats. AB - In order to apply the phase spectral analysis of auditory brainstem response (ABR) to the clinical diagnostic test, the phase spectra of ABRs were investigated under adequate stimulus intensity in normal cats and after the destruction of acoustic nerve and brainstem auditory pathways in cats. The results were as follows; i) In normal ABRs, the phase spectra were mainly composed of three frequency components at 0-300 Hz (component A), 300-900 Hz (component B) and 900-1500 Hz (component C). ii) A greater decrease of the component synchrony measure (CSM) occurred if ipsilateral destruction was performed in a peripheral lesion. Lesions of the auditory pathway were followed by a decrease of the CSM of component C in response to contralateral stimulation. These results suggest that the phase spectral analysis of ABRs has significant clinical value in the detection of brainstem lesions. PMID- 8203245 TI - ABR topographic mapping with digital filtering using fast Fourier transform. AB - The power spectrum of normal ABR consists of three major parts: low (0-350 Hz: component A), middle (350-700 Hz: component B) and high (700-1200 Hz: component C) frequency components. With digital filtering using fast Fourier transform (FFT), three component waveforms of ABR were obtained and designated as component A, B and C. Component A has a positive peak which corresponds to wave V or the slow component of the original ABR. Component B has three positive peaks (B1-B3) which correspond to wave I, III and V, and component C has five positive peaks (C1-C5) which correspond to wave I-V. These three component waveforms of ABR were analyzed topographically in normal hearing adults and cats. In addition, changes in the topography of three component waveforms of ABR were studied in a series of experimentally induced lesions in the brainstem auditory pathway in cats. The following results were obtained: i) The highest voltage (HV) area of component B1 was detected on the ipsilateral side in normal adults and cats. The HV areas of component C1, C2 and C3 in normal adults and C1, C2 in normal cats were detected on the ipsilateral side. ii) There was a correlation between changes in component C and the lesion site of the auditory pathway. Component C appears to be the most sensitive indicator of the lesion site of the brainstem. PMID- 8203246 TI - Pure-tone threshold prediction by 80-Hz amplitude-modulation following response. AB - The usefulness of 80-Hz amplitude-modulation following response (AMFR) detected by phase spectral analysis to predict the hearing threshold during sleep was evaluated in 20 normal adults, 8 normal children and 37 children with hearing impairment. The onset effect of tonal stimulus on 80-Hz steady state response was studied in normal adults during sleep and a threshold of 80-Hz AMFR detected by phase spectral analysis was compared with that of ABR elicited by tone pips in children during sleep. Although 80-Hz AMFR is not appropriate for the assessment of hearing in adults, it appears useful for evaluating hearing in young children during sleep. Hearing prediction by 80-Hz AMFR appears to be more accurate than that by ABR elicited with tone pips. The onset effect of stimulus on 80-Hz AMFR with modulation depth of 95% was less than 80-Hz SSR evoked by clicks. PMID- 8203247 TI - Measurement of cochlear basilar membrane traveling wave velocity by derived ABR. AB - Auditory brainstem response (ABR) can be used to measure the basilar membrane traveling wave velocity (TWV). Traveling wave velocity was calculated from the latency difference between wave V of different derived ABR and the cochlear location distance between the appropriate derived band center frequency. The latency of wave V of derived ABR produced by 6 noise-masked ABR using high pass filtered noise and the location of the corresponding cochlear partition (distance from the stapes foot-plate) were measured, and five traveling wave velocities were estimated based on this parameter. Ten subjects with normal hearing, 7 patients with Meniere's disease, and 8 patients with sensorineural hearing loss were used in this study. The traveling wave velocity in the sensorineural hearing loss group was within normal limits at all frequencies, whereas the traveling wave velocity at 8 kHz in the Meniere group greatly exceeded that of the normal and sensorineural hearing loss group. PMID- 8203248 TI - Acoustic neuroma presented as repeated hearing loss. AB - Up to 15% of patients with acoustic neuroma may have a history of sudden hearing loss. Recovery from sudden hearing loss with acoustic neuroma is rare. In this paper, a case of bilateral acoustic neuromas presented as repeated sudden hearing loss with recovery on the left side after removal of right-sided tumor were reported. She experienced three episodes of sudden hearing loss, showing various types of audiograms and ABR on the left side. There was no relationship between the type of audiograms and ABR findings. Factor influencing ABR might be different from the cause of hearing impairment. Acoustic neuromas can be reliably identified by performing MRI properly. However, MRI showed negative scan and ABR finding was abnormal in the first episode of our case. ABR continues to be a sensitive diagnostic back-up test to MRI for the detection of acoustic neuromas. Even if the patient, who showed abnormal ABR findings suggesting retrocochlear pathology, showed normal MRI, acoustic neurinoma should not be ruled out and both ABR and MRI must be re-examined at regular intervals. PMID- 8203249 TI - Effects of aging on hearing results in tympanoplasty. AB - The effects of aging on the preoperative and postoperative hearing results of tympanoplasty were assessed in 642 patients with chronic suppurative otitis media (COM) or cholesteatoma (CHL). Analysis focused on the correlation between hearing results and age for each disease and type of tympanoplasty. Data were evaluated by calculating the regression line, mainly using second order polynomial regression analysis. Averaged air and bone conduction thresholds (PTA) in patients were appreciably poorer in younger patients and increased with age, compared with physiological hearing impairment in old age (presbyacusis). Regression lines for PTA of air and bone conduction in patients and for normal data (air conduction) separated from each other after the age of 30 and hearing impairment gradually accelerated with age. Means of air-borne gap, however, were almost the same in each age group, though hearing thresholds in individual patients were distributed widely. This was more dominant in patients who had undergone type III or IV tympanoplasty than those with type I tympanoplasty, and in patients with COM than with CHL. Labyrinthine function thus appears to be gradually aggravated with age in patients with chronic inflammatory ear disease. Patients with chronic otitis media should be thus recommended to undergo tympanoplasty at an early age. PMID- 8203250 TI - Electrocochleography in the diagnosis of delayed endolymphatic hydrops. AB - It is known that delayed endolymphatic hydrops (DEH) occurs in patients with unilateral and/or bilateral profound hearing loss. In the ipsilateral and bilateral types of DEH, no audiological tests can be performed on the affected ear because of profound deafness, although these tests can be done in the contralateral type. Electrocochleography (ECochG) was recorded on better hearing ears in both types of DEH. The results showed an increased negative summating potential (SP) in 6 out of 10 contralateral DEH patients whereas it could be measured in only one of 10 ipsilateral DEH patients. The mean SP/AP ratio of the contralateral type was 0.42 which was significantly larger than that of the ipsilateral type. The results suggest that contralateral-type DEH has the same pathology in the cochlea as Meniere's disease, and that ECochG can distinguish between these two types of DEH. PMID- 8203251 TI - Frequency analysis of transiently evoked otoacoustic emissions in sensorineural hearing disturbance. AB - Transiently evoked otoacoustic emissions (TEOAE) are present in nearly all normal hearing ears and recognized as useful for objective auditory screening. In the spectral analysis of TEOAE with click stimuli, the normal power spectrum of TEOAE has yet to be obtained. In this study, the normal range of the power spectrum was determined for 42 adults with normal hearing and compared with sensorineural hearing disturbance data. The power spectrum of TEOAE in normal hearing adults sloped down at high frequencies and was the same for right and left ears in both males and females. For comparison with sensorineural hearing disturbance, a significant correlation between the audiogram and power spectrum of TEOAE was sought. Frequency specificity was noted in the power spectrum of TEOAE with click stimulation. PMID- 8203252 TI - Slow saccades and quick phases of nystagmus after pontine lesions. AB - A patient was referred to the university hospital to test eye movements after she had suffered cerebellar hemorrhage one month previously. Examination showed a selective deficit of saccades and quick phases of nystagmus toward the lesion site in the horizontal plane, which was later confirmed pathologically, and which corresponded precisely to the paramedian pontine reticular formation (PPRF). This may suggest that velocities in the quick phase of nystagmus, whether visual or vestibular, and saccades show the same result in PPRF lesion and they share the same neural circuitry in cells located in the PPRF. In the present study, the non linear saccade velocity-amplitude equation was best-fitted to this patient. Quantitative evaluation of the quick phase may provide a simple and quick reference in saccade slowing. PMID- 8203253 TI - Quantitative assessment of influence of aging on optokinetic nystagmus. AB - A quantitative assessment of the influence of aging on optokinetic nystagmus (OKN) was investigated using 50 normal adults in ages ranging from 30 to 70 years. In linear stimulus-induced OKN, a statistically significant difference was demonstrated in slow-phase OKN velocity only between the 30-59 year old age group and the 70-79-year-old age group, when OKN stimulus was more than 60 degrees/s. Step stimulus-induced OKN was investigated in the same age groups in order to compare aging effects upon slow-phase OKN velocity. No statistically significant difference was found in slow-phase OKN velocity between younger age groups and the oldest age group. There was no significant difference in fast-phase velocity among the age groups. Thus, step-induced OKN has a wider clinical application than linear stimulus-induced OKN. PMID- 8203254 TI - Anti-idiotypic antibodies from the mother may influence the immune response of the fetus and newborn. PMID- 8203255 TI - An extrapancreatic action of diazoxide to inhibit glucose transport activity on adipocytes. AB - The effect of diazoxide on 3-O-methylglucose (3-O-MG) transport was studied in isolated rat adipocytes to elucidate its extrapancreatic action. Diazoxide (0.3-3 mmol/L) significantly inhibited 3-O-MG uptake into adipocytes in a basal state or an insulin-stimulated state. The inhibitory effect was mainly due to the inhibition of insulin responsiveness for 3-O-MG uptake. The insulin responsiveness is determined by the capacity in the process of insulin action and in the final glucose transport activity, and diazoxide mainly inhibited the 3-O MG transport activity itself. Based on these findings, this extrapancreatic action of diazoxide is considered to contribute partially to raising the blood glucose level in children receiving the drug. Diazoxide, as a glucose transport inhibitor, may be a useful tool for studying the issues related to glucose transport or insulin action. PMID- 8203257 TI - Specific IgE antibodies and serum eosinophil cationic protein in children with atopic dermatitis alone. AB - Both eosinophils and specific immunoglobulin E (IgE) to foods and mites have been considered involved in the pathogenesis of atopic dermatitis (AD). The relationship between eosinophils and specific IgE, however, remains to be elucidated. Blood eosinophil counts, serum eosinophil cationic protein (ECP) and IgE to egg white, cow's milk, soybean, rice and Dermatophagoides pteronyssinus (Dp) were measured in subjects with AD alone or bronchial asthma (BA) alone. Subjects with positive IgE titers (Pharmacia radioallergosorbent test (RAST) units > 0.7) of one or more items were defined as RAST-positive. Immunoglobulin E titers to egg white, cow's milk and soybean of subjects with AD were high in early childhood and declined with aging, whereas the titers of subjects with BA were negative or low. Immunoglobulin E titers to Dp were elevated after 1 year of age in both disease groups. Eosinophil cationic protein (ECP) levels and blood eosinophil counts in the AD and BA groups were significantly higher than those of non-atopic controls. No difference in ECP levels or blood eosinophil counts were observed between RAST-positive and negative groups. It is concluded that IgE to foods such as egg white, cow's milk and soybean might have a role in the pathogenesis of AD of young children, while IgE to mites might be involved in older children. Eosinophils may also participate in AD. However, different mechanisms may be responsible for the rise in specific IgE and high ECP levels and blood eosinophil counts. PMID- 8203256 TI - A study of urinary metabolites in patients with dicarboxylic aciduria for differential diagnosis. AB - Dicarboxylic aciduria (DCA-uria) is a relatively common finding in the screening of organic acidemias by gas chromatography/mass spectrometry (GC/MS). A considerable number of patients with DCA-uria are involved in disturbances of mitochondrial and peroxisomal fatty acid beta-oxidation. The differential diagnosis of DCA-uria was investigated using a combination of organic acid analysis by GC/MS, carnitine determination, acylcarnitines by fast atom bombardment/mass spectrometry (FAB/MS) and acylglycines by stable-isotope dilution analysis. The relative distribution of urinary metabolites was examined in 46 patients with DCA-uria of different origins, including physiological ketosis of childhood, disorders of propionic acid metabolism, glutaric aciduria type II, Zellweger syndrome and patients who were clinically diagnosed as having Reye syndrome. Zellweger syndrome seemed to be distinguishable from other disorders by the high sebacic acid/adipic acid ratio of DCA-uria and increased excretion of 4-hydroxyphenyllactic acid and 2-hydroxysebacic acid. The mild form of glutaric aciduria type II was often missed by current organic acid analysis alone, but was readily diagnosed by acylcarnitine and acylglycine determination. The ratio of free/total carnitine was low in most of the DCA-uria patients except for two of five cases of Zellweger syndrome and one of three cases of Reye syndrome. The acylcarnitine analysis by FAB/MS showed adipyl-, suberyl-, sebacyl- or dodecanedioylcarnitine as major peaks in most of these patients, although these were not specific. Disease-specific peaks were detectable only in congenital organic acidemias such as glutaric aciduria type II, methylmalonic acidemia and propionic acidemia. PMID- 8203258 TI - Effect of specific immunotherapy in Dermatophagoides pteronyssinus allergic children. AB - The effect of immunotherapy on 21 Dermatophagoides pteronyssinus (Dpt)-sensitive patients (15 children with extrinsic asthma and six children with extrinsic asthma plus allergic rhinitis) aged 8.9 +/- 0.71 years was studied. Their subjective and objective respiratory symptom score was recorded before beginning and after the first year of immunotherapy. The respiratory subjective symptoms, such as cough day/night, running nose, sputum production, sneezing, shortness of breath at night and asthma attacks, decreased significantly from pretreatment level (P < 0.05). The objective symptoms, such as wheezing, dyspnea with prolonged expiration, sibilant rales and retractions score, gradually decreased during treatment (P < 0.01). Total eosinophil count decreased in 76.2% of patients after immunotherapy (P < 0.01). While total immunoglobulin E (IgE) decreased in 81% of patients and specific IgE for Dpt decreased in 90.5% of patients, specific IgG for Dpt increased in 76% of patient (P < 0.001). Our results suggested that rising IgG and falling IgE values do not always coexist in the patients who benefit from immunotherapy. PMID- 8203259 TI - A study of the iron requirement in infants, using changes in total body iron determined by hemoglobin, serum ferritin and bodyweight. AB - The amount of iron absorption in healthy breast-fed infants was estimated in order to assess the iron requirement. This was carried out by monitoring changes in total body iron (TBI). Hemoglobin and serum ferritin were measured to calculate hemoglobin iron, body storage iron and TBI at the ages of 4-5 months and 10-11 months. The amount of iron absorption was approximately 0.4 mg/day, calculated as the sum of TBI increment and physiological iron loss. From this study, the dietary iron requirement for the weaning period was estimated as 4 mg/day. PMID- 8203260 TI - Efficacy of synchronized IMV on weaning neonates from the ventilator. AB - This study evaluated the efficacy of a new patient-triggered ventilator that triggered the patient's inspiratory effort by detecting the change in airflow by means of a 'hot wire' anemometer. This ventilator was used in both the conventional and the synchronized intermittent mandatory ventilation (SIMV) modes in seven neonates. Values for blood gas, spontaneous breathing rate, tidal volume of spontaneous breaths and minute volume were compared in all seven neonates. The resistive work of spontaneous breathing in five neonates, obtained with synchronized intermittent mandatory ventilation was compared with the values obtained using conventional mechanical ventilation on the previous day of weaning from the ventilator. At each the inflation time studied (0.4, 0.3, 0.24 s), all mechanical breath occurred synchronously with infants' inspiratory efforts. The median trigger delay was 80 ms. Oxygenation was improved on the new system compared with the conventional system. Tidal volume of spontaneous breathing and minute volume were increased with SIMV compared with conventional mechanical ventilation, although the resistive work of spontaneous breathing was decreased with SIMV. The tidal volume of spontaneous breaths was more constant with SIMV versus conventional mechanical ventilation. Thus, the airway flow-triggered SIMV may lessen inspiratory muscle fatigue during weaning process. We conclude that the SIMV is useful in weaning neonates from the ventilator. PMID- 8203261 TI - Helicobacter pylori colonization in children with gastritis and peptic ulcer. I. The colonization rate and effects of colonization on mucin content and mucosal inflammation in the antrum. AB - The incidence of Helicobacter pylori infection and effects of H. pylori colonization on mucin content and mucosal inflammation of the antral mucosa were studied quantitatively in 55 Japanese children with suspected gastritis and peptic ulcers (aged 6-16 years, mean 12.3 years). H. pylori was detected, using Warthin-Starry stain, in nine of the 22 cases (41%) with antral histological gastritis, but in none of the 33 histologically normal cases. Five out of seven duodenal ulcer cases showed histological gastritis, and all five cases were H. pylori positive. Severity of gastritis, evaluated by means of gastritis score, was significantly higher in H. pylori positive gastritis cases than in H. pylori negative gastritis cases (5.4 +/- 1.0 vs 3.1 +/- 0.3, P < 0.001). A PAS-AB index, a proportion of the periodic acid Schiff-alcian blue (PAS-AB) positive mucin area to the total epithelial area, was significantly lower in H. pylori positive cases than in H. pylori negative cases, irrespective of the existence of histological gastritis (23.5 +/- 7.6% vs 40.4 +/- 5.5%, 43.5 +/- 4.2%, P < 0.001). The decreased mucin content of gastric mucosa is likely to lead to weakening of an important defensive factor of gastric mucosa. These findings suggest that H. pylori plays an important role in gastritis and peptic ulcers in children, especially in cases with duodenal ulcer. PMID- 8203262 TI - Helicobacter pylori colonization in children with gastritis and peptic ulcer. II. Ultrastructural change of the gastric mucosa. AB - To evaluate the role of Helicobacter pylori in the pathogenesis of gastritis and peptic ulcer in children, ultrastructural changes of the gastric mucosa with H. pylori colonization were studied in two pediatric patients with duodenal ulcers. The study demonstrated that H. pylori: (i) colonized the mucous layer covering normal gastric epithelium; (ii) lay atop short, irregular microvilli and at the intercellular junctions of damaged cells; and (iii) adhered firmly by specific junction zone (firm connection) and loosely by filamentous appendages to the epithelial surfaces of cells which lacked evidence of a protective mucous layer. The ultrastructural changes, which become progressively worse from patterns (i) to (iii) mentioned above, suggest that these patterns represent distinct and successive stages of the infection. These findings, therefore, lend support to the notion that H. pylori infection is quite common and may relate to the pathogenesis of gastritis and peptic ulcer in children as well as in adults. PMID- 8203263 TI - Circadian rhythm of the autonomic nervous system in long QT syndrome. AB - The circadian changes in the activity of the autonomic nervous system in a group showing long QT duration in electrocardiogram (ECG) were studied in order to differentiate symptomatic congenital long QT syndrome from asymptomatic. The asymptomatic group presented only long QT duration (QTc > 0.46). Seven girls and two boys, including two subjects experiencing syncope of non-neurological origins, were examined by using heart rate (HR) power spectrum analysis. In three subjects, the peak of the high frequency band, indicating the parasympathetic activity, disappeared during night-time (sleep), which means the possibility of a high risk of sudden cardiac death. In two of three subjects, moreover, the averaged sympathetic activity during daytime was significantly increased compared to that during night-time, in addition to the abrupt increase of sympathetic activity in the morning. These two subjects, in which one boy had a family history of Romano-Ward syndrome, were the same people experiencing the syncope attack. We succeeded in objectively elucidating that congenital long QT syndrome is adrenergic-dependent, and suggest that HR power spectrum analysis may be of value in distinguishing symptomatic congenital long QT syndrome from asymptomatic showing only long QT duration. PMID- 8203264 TI - A new oral margarine loading test in children. AB - Margarine (2g/kg) was orally administered to 39 children with normal fat digestion and absorption (control group) and 17 children with abnormal fat digestion and absorption (malabsorbed group). The serum triglyceride (TG) level was serially determined by capillary blood sampling. In the control group, the TG level was significantly elevated after 2, 3 and 4 h as compared with the level before margarine ingestion (basal TG). The maximum TG elevation rate [MTER = (maximum TG-basal TG)/basal TG x 100] was > 50% in all but three children. In contrast, a significant increase in TG was not observed in the malabsorbed group after margarine ingestion, and the MTER was < 50% in all but two children. The MTER was significantly lower in children with a high microscopic score of fecal fat than that in children with a low score. This oral margarine loading test is a simple and semi-quantitative evaluation of fat digestion and absorption, and is considered to be useful for the assessment of the presence or severity of fat maldigestion and malabsorption in children. PMID- 8203265 TI - Clinical variability of congenital myopathy with type 1 fiber atrophy: a long term observation of three cases. AB - The variable clinical courses of three cases of congenital fiber type disproportion (CFTD) over a period of 10 years are presented. All showed improvement in early childhood, but subsequently, varying degrees of deterioration were noted: specifically, marked deterioration in case 2 and decreased muscle strength in case 3. Maximal motor function levels were attained differently among the cases. Histological findings included type 1 fiber hypotrophy and increased internal nuclei in common in all cases. Fine structural changes, such as patchy areas of myofibrillar degeneration, were noted in cases 1 and 2 (second biopsy), and cytoplasmic bodies were seen in case 2 (second biopsy). Myotubes were noted in case 3. The degree of cyto-architectural changes did not correlate with clinical severity. The heterogeneity of CFTD is also discussed. PMID- 8203266 TI - Differential alpha-smooth muscle actin expression in a gastric epithelioid leiomyosarcoma in a 14 year old girl. AB - Leiomyosarcoma in childhood is very rare. This report describes the immunohistochemical study of a gastric epithelioid leiomyosarcoma in a 14 year old girl. Microscopically, the tumor showed two distinct histological patterns within the same tumor: small epithelioid cells forming a lobular pattern and spindle-shaped cells forming interlacing fascicles, but no distinct border divided the two types of cells. Immunohistochemically, vimentin was positive in all tumor cells; alpha-smooth muscle actin, however, was negative in small epithelioid cells and positive in spindle-shaped cells. The data revealed that the tumor had components showing two stages of morphological and biochemical differentiation. This case indicates that leiomyosarcomas might lose smooth muscle actin during malignant transformation; or, alternatively, they might arise from a primitive type of smooth muscle cell and some of them could spontaneously differentiate into mature smooth muscle cells, expressing this actin. PMID- 8203267 TI - Erythromycin improves gastrointestinal motility in extremely low birthweight infants. AB - Erythromycin (EM) was administered to five extremely low birthweight infants (ELBWI) with delayed enteral feeding to evaluate the clinical effect on severely impaired gastrointestinal motility. Five patients studied responded well to EM administration without any adverse effects during the course. Four patients were given 15-30 mg/kg per day EM intravenously as a loading and thereafter 3-5 mg/kg per day as a maintenance dose. One patient responded well without loading. The infants could be fed enterally 4, 5, 6, 4 and 2 days after the initiation of EM administration, respectively. Erythromycin administration is a safe and useful way to facilitate gastrointestinal motility in ELBWI who require prolonged ventilator support with an increased risk for nutrient deprivation. PMID- 8203268 TI - Renal impairment in very low birthweight infants following antenatal indomethacin administration. AB - Three cases of neonatal renal insufficiency in very low birthweight (VLBW) infants following repeated antenatal administration of indomethacin to prevent premature labor are reported. Three pregnant women received indomethacin (total doses of 150-850 mg) for 3-14 days from admission until delivery. The gestational ages and birthweights of the infants ranged from 24 to 28 weeks and 612 to 1432 g, respectively. Oliguria, early onset of hyperkalemia and prolonged renal dysfunction occurred after birth. Renal failure did not improve in one infant. Despite the efficacy of indomethacin for tocolysis in premature labor, VLBW infants born after repeated maternal administration near the time of delivery may have developed impairment of the premature kidney. PMID- 8203269 TI - A case report of placental hemangioma resulting in severe fetal distress. AB - A 30 year old female was admitted twice during her pregnancy for genital bleeding. An ultrasonography at 19 weeks gestation showed several nodules on the chorionic plate. Cardiotocography during labor at 37 weeks gestation indicated a non-reactive pattern. A 2230 g infant girl was delivered soon after rupture of membranes with asphyxia and hydrops fetalis. The placenta weighed 600 g with a maximal thickness of 6 cm. Nodules occupied about one-third of the placenta and were diagnosed as placental hemangiomas. Postnatal examination revealed that the infant had disseminated intravascular coagulation and cardiac failure. This baby recovered after treatment in the intensive care unit, and was discharged home on the 52nd day of life. PMID- 8203270 TI - Severe aplastic anemia in a patient with primary immunodeficiency. AB - This paper reports the case of a 6 year old boy with primary immunodeficiency disease, whose marrow cells showed dyshematopoietic features, that was subsequently transformed to severe aplastic anemia. He was first diagnosed as having congenital immunodeficiency comprising deficiency of immunoglobulin A (IgA), IgG2 and IgG4, depressed mitogen responses, lymphopenia with inverted CD4/CD8 ratio and an increased proportion of T-cell receptor gamma/delta-bearing cells. Cytogenetic study of the peripheral blood showed a normal karyotype of 46,XY, but that of the marked hypoplastic marrow demonstrated one cell with monosomy 7 and another with trisomy 8 in the 20 cells examined. PMID- 8203271 TI - Transient erythroblastopenia due to human parvovirus B19 infection: a case report of a boy suffering from purpura. AB - Transient erythroblastopenia of childhood (TEC) was observed in a boy infected by human parvovirus B19 (B19) before the manifestation of the typical clinical picture of erythema infectiosum (EI). He did not have any apparent symptoms of anemia, and spontaneous resolution of erythroblastopenia was observed before the manifestation of the symptoms of EI. The difference between primary B19 infection and classical TEC is discussed. PMID- 8203272 TI - Haemophilus influenzae type D infection and IgG2 deficiency in a patient with chronic mucocutaneous candidiasis. AB - A 14 year old boy with chronic mucocutaneous candidiasis and persistent pulmonary infection caused by Haemophilus influenzae and Streptococcus pneumoniae is reported. Initial bacterial culture studies showed H. influenzae type B and S. pneumoniae as causative agents. H. influenzae type D was constantly isolated from the patient's sputum. Abnormally low levels of serum immunoglobulin G2 (IgG2) found in the patient may have contributed to the pulmonary infection and H. influenzae type D may be an important causative agent in immunodeficient patients. PMID- 8203273 TI - Cough variant asthma: a case study with antigen, histamine and methacholine inhalation challenge tests. AB - This paper presents a 7 year old girl with cough variant asthma, in which house dust challenge test provoked fine crackles on auscultation without any changes of lung function test. Pretreatment with DL-chlorpheniramine maleate for 7 days inhibited the appearance of fine crackles. On histamine inhalation test, fine crackles and rhonchi appeared on auscultation without bronchoconstriction (% fall of one-second forced expiratory volume < 10%). These data suggest that the cause of cough variant asthma is mainly an immunoglobulin E-mediated allergic reaction in the mucus secreting system. PMID- 8203274 TI - Pharmacokinetic investigation with 125I labeled T-actemodulin (TAM). AB - The aim of the study was to label TAM with radioactive iodine and to follow its distribution in different organs of rats. T-actemodulin is a thymic hormone isolated from calf thymus by a new technology. TAM was labeled according to the method of Greenwood and Hunter. Two major peaks were observed on the gel chromatography: The first peak contained the labeled TAM; the second peak contained 125I which was not bound to the organic compound. Additional purification of the first peak was performed on a Sephadex G-75 column, and the eluate was designated as purified peak I. After a radioimmune testing it could be concluded that TAM was labeled successfully and the peak I contained 125I-TAM. Peak I, purified peak I and the peak II were applied to young male Wistar rats. The radioactivity of pancreas, kidney, spleen, adrenals, liver, thymus, bone marrow, testis and thyroid were measured after killing the animals 10 min, 60 min, and 24 h after the injections. The pharmacokinetic study showed that all organs, except for the thyroid have a higher affinity for labeled TAM than for the free 125I. Higher accumulation of labeled TAM was observed in the pancreas, kidney, adrenals and spleen. A specific uptake of labeled TAM in these organs can be suggested. Functional interrelations between thymus and pancreas, spleen, adrenals are discussed. PMID- 8203275 TI - Evaluation of ondansetron as a drug for premedication. AB - The potency of Ondansetron (Zofran, Glaxo), a highly specific 5HT3 antagonist in preventing the very unfavorable complication during introducing anesthesia, i.e. a Bezold-Jarisch reflex-like reaction, was studied in a clinical trial. A total of 20 patients (12 males and 8 females aged 19-65 years) admitted for clinical surgical treatment participated in the trial. Zofran (8 mg in 500 ml Ringer solution) was injected intravenously one hour before intubation at a flow rate of 8 ml. min-1. Systolic and diastolic blood pressure, central venous pressure, breathing frequency and minute ventilation, pCO2 and pO2 in venous blood, electrocardiogram monitoring (ECG) and several common features such as spontaneous muscle activity, palpebral reflexes, skin and mucose surfaces were continuously observed. Visual, auscultatory and X-ray control of the lungs was effected. It was found that blockade of 5HT3 receptors prevented the appearance of Bezold-Jarisch reflex-like reaction. The drug could successfully be used in anesthesiological practice. PMID- 8203276 TI - Auditory stimulus pattern discovering in paranoic schizophrenia patients. AB - Nine paranoic schizophrenia patients and nine controls participated in the study aimed at revealing differences in their ability to discover a pattern of auditory stimuli and to react to changes in environmental probability structure. Two kinds of auditory stimuli were used: high--1200 Hz (H) and low--800 Hz (L), both of 50 msec duration and 60 dB intensity. The experimental series were: series 1 (S1)- simple motor reaction to 50 L tones; series 2 (S2) and series 3 (S3) were identical--a cycle signal pattern (HHLHLL) of 102 tones. In S2 the instruction required choice motor reaction to L tone and in S3, also discovering the tone sequence and its verbal announcement. Patients discovered the stimulus pattern at the 28th and controls at the 30th signal. RT of patients in all series was longer than that of controls. Each of the factors "group" (controls/patients) and "experimental series" had a significant influence on RT. The possibility of interpreting these results as connected with an extrasensor mechanism dysfunction is discussed. PMID- 8203278 TI - Selective enhancement of glutathione S-transferase activity in liver and extrahepatic tissues of rat following oral administration of vanadate. AB - The effect of oral administration of vanadate (100, 200 and 400 nM for 30 days) on the activity of the detoxifying enzyme system glutathione S-transferase (GST) in rat liver and in several extrahepatic tissues was examined. Vanadate showed a high activity as GST inducer in liver and in small intestine mucosa followed by large intestine mucosa and kidney in a dose-dependent manner. No significant alterations in GST activity were observed in forestomach and lung tissues after vanadate. Vanadate treatment that resulted in an enhancement of GST activity impaired neither hepatic nor renal function as evidenced by serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, sorbitol dehydrogenase, urea, and creatinine. Since the ability to induce an increase of detoxifying enzyme activity by anticarcinogenic agents was found to correlate with their activity in the inhibition of tumorigenesis, the trace element vanadium might be considered a potential cancer chemopreventive agent. PMID- 8203277 TI - Impairment of learning and memory in shuttle box-trained rats neonatally injected with 6-hydroxydopamine. Effects of nootropic drugs. AB - The effect of neonatal 6-hydroxydopamine (6-OHDA) treatment on learning and retention and on the level of biogenic monoamines in some brain structures as well as the influence of the nootropic drugs--piracetam, aniracetam, meclofenoxate and fipexide on the 6-OHDA-induced effect was studied. Two- way active avoidance (shuttle box) was used. The levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the frontal cortex, striatum, hypothalamus, hippocampus and pons were measured. In mature rats, injected with 6-OHDA (100 mg/kg s.c.) in the first 3 postnatal days learning and retention were impaired and the NA level in the frontal cortex and hippocampus was decreased. Piracetam (600 mg/kg), aniracetam (50 mg/kg), meclofenoxate (100 mg/kg) and fipexide (10 mg/kg) administered orally 5 days before and 5 days during training, abolished the amnestic effect of 6-OHDA and restored to control values the NA level in the frontal cortex and hippocampus. This finding suggests the important role of the noradrenergic neurotransmitter system in the 6-OHDA-induced amnesia, as well as in the favorable effect of the nootropic drugs tested on 6-OHDA-impaired memory processes. PMID- 8203279 TI - Effects of propranolol, pindolol and atenolol after multiple administration in rats on the duration of hexobarbital sleeping time and on the activity of some drug-metabolizing enzyme systems. AB - Three beta-adrenergic blocking agents propranolol (50 mg/kg), pindolol (5mg/kg) and atenolol (150mg/kg) were administered orally in rats for 21 days. The duration of hexobarbital (HB) sleeping time and the activities of some liver monooxygenases and synthetases were studied. The HB sleeping time was not changed. Propranolol and pindolol decreased the ethylmorfin-N-demethylase (EMND) and benzphetamine-N-demethylase (BND) activities. The three beta-adrenergic blocking agents did not change the activities of anilinehydroxylase (AH), ethoxycoumarine-O-demethylase (ECOD), and glutathione-S-transferase (G-S-T), the total content of cytochrome P-450, b5 and microsomal heme. They increased the activities of uridinediphosphoglucuronil transferase (UDPGT) and NADPH-cytochrome C reductase. The participation of different mechanisms of the effects of the three beta-adrenergic blocking agents on the activity of drug-metabolizing enzyme systems was discussed. PMID- 8203280 TI - Effects of nimodipine and flunarizine on the regional autoregulation of the CBF in cats. AB - The effects of nimodipine (3 micrograms/kg/min) and flunarizine (60 micrograms/kg/min) on the autoregulation of the regional cerebral blood flow (rCBF) in the cortex and thalamus of 28 cats were studied. The animals were anaesthetized with ether and alfa-chloralose. The rCBF was registered by the hydrogen clearance method with locally generated hydrogen. MABP elevation was performed by i.v. angiotensin infusion (0.2 +/- g/min). The initial values of the rCBF in the cortex were 71.1 ml/100g/min, and in the thalamus - 49.1 ml/100g/min. The limits of rCBF autoregulation in the cortex were: the absolute limit of autoregulation (La) 139 +/- 11 mm Hg, and the relative limit of autoregulation (Lr), 28 +/- 6 mm Hg. In the thalamus these values were: La 160 +/- 11 mm Hg, and Lr 47 +/- 7 mm Hg. Nimodipine increased the rCBF in the cortex by 58 per cent, and in the thalamus, by 38 per cent as compared to the initial values (p < 0.01). The limits of rCBF autoregulation in the cortex changed to 88 +/- 8 mm Hg for the La, and to 10 +/- 4 mm Hg for the Lr (p < 0.01); and in the thalamus, to 92 +/- 8 mm Hg for the La, and to 19 +/- 5 mm Hg for the Lr (p < 0.01). Flunarizine increased the rCBF in the cortex by 28 per cent, and in the thalamus by 24 per cent, as compared to the initial values (p < 0.01). The rCBF autoregulation in both cerebral structures was not influenced by flunarizine. PMID- 8203282 TI - Changes in the electrical activity of the gastric remnant after Billroth II gastrectomy in dogs. AB - Chronic experiments were performed on dogs with Biller II gastrectomy followed by Roux-Y gastrojejunostomy. Gastric mucosa valve was made in the region of the gastrointestinal anastomosis in order to prevent the rapid gastric evacuation. Electrical activity of the gastric remnant, duodenum and jejunum was led off by six bipolar, silver, ball-shaped electrodes, implanted subserously on the muscle wall. Continuous bursting of groups of spike potentials with the slow gastric potentials in the usual rhythm (4.5-5 cpm) occurred during the 1st month after surgery. However, at the end of the 2nd month after surgery there were periods of tachygastria. The frequency of the gastric potentials was lower (7.52 +/- 1.37 cpm, n = 26) or higher (20.40 +/- 0.68 cpm, n = 30) compared to that of the jejunal slow waves (14.11 +/- 0.18 cpm, n = 50), i.e., it was different from the frequency of the jejunal slow waves. PMID- 8203283 TI - Effects of piracetam on erythropoiesis and leukopoiesis in rats. AB - Erythro- and leukopoiesis in rats after 10-day treatment with piracetam (2 x 200 mg/kg b.w.) were studied. Increase of reticulocytes and of 59-iron incorporation in newly formed erythrocytes accompanied by an increase of the index of maturation of erythroblasts in bone marrow were found suggesting a piracetam induced stimulation of erythropoiesis. Piracetam also increased the number of small lymphocytes and the maturation of granulocytes in bone marrow. It is supposed that piracetam exerting a positive effect on the metabolic processes of erythroid, myeloid and lymphoid precursors stimulates their proliferation and differentiation. PMID- 8203281 TI - Effects of subchronic exposure of rats to lead or zinc on alpha-adrenoceptor mediated contractile responses in isolated vas deferens. AB - The effects of subchronic (30 days) drinking water exposure of rats to ZnSO4 or Pb(CH3COO)2 alone or in combination on the adrenergically-mediated contractile responses of isolated vas deferens were studied. The contractile effects of the alpha 1, alpha 2-adrenoceptor agonist noradrenaline (NA) and to the alpha 1 adrenoceptor agonist 1-phenylephrine (1-PhE) were decreased after zinc exposure, whereas after lead exposure or lead plus zinc exposure they were not changed. The contractile responses to field electrical stimulation (FES, 0.1 Hz, 1 msec, 80 V) were diminished in amplitude in all metal-treated preparations as compared to controls. The yohimbine-induced restoration of the clonidine inhibited contractions in response to FES was decreased in both lead- and zinc-treated preparations, the EC50 for yohimbine being 0.018 +/- 0.001 microM in control preparations, 0.073 +/- 0.019 microM in lead-treated preparations and 0.056 +/- 0.021 microM in zinc-treated preparations. The calcium-channel blocker verapamil was found to inhibit at low concentrations and to increase at higher concentrations the FES-induced contractile responses in preparations from zinc exposed rats. The inhibitory effect of cumulatively applied nitrendipine on the FES-induced contractions was increased in both lead- and zinc-treated smooth muscles, but was not altered in the preparations from lead plus zinc-treated rats. Therefore, subchronic exposure to subtoxic doses of lead of zinc led to different changes in the adrenergically-mediated contractility of isolated vas deferens. The changes induced by zinc exposure were not observed after lead plus zinc exposure. All these findings might be of pharmacological, toxicological or clinical importance. PMID- 8203284 TI - The metallothionein structural motif in gene expression. AB - Metalloregulation in eukaryotic organisms is poorly understood. Only a limited number of physiological processes are currently known to be regulated by metal ions. Copper salts stimulate transcription of MT and SOD genes in fungi and repress expression of cytochrome c6 in algae. The Cu-activation of gene expression in fungi is mediated by a Cu1+ specific sensor protein. The mechanism of Cu-activation of the sensor molecule, ACE1 (and probably AMT1), appears to be the formation of a CuS polymetallic cluster as the structural core of the proteins. Structural similarities between ACE1, AMT1 and metallothionein suggest that the MT motif is a good structural model to explain the metal-specific activation and specificity of the two signal transducing proteins. Metal ion specificity is achieved by the propensity of proteins with a MT motif to form multinuclear CuS centers. Coordination inorganic chemistry appears to be the driving force for Cu1+ metalloregulation in biology. The metalloregulation of transcriptional activation of mammalian MT genes will be intriguing as metal ion selectivity is not as apparent. The MT motif is not expected to be a highly redundant structural theme. The intriguing observation by Uchida et al. (154) that the growth inhibitory factor (MTIII) deficient in the brains of Alzheimer's patients is homologous to metallothioneins raises the likelihood that coordination chemistry will be critical in stabilizing the bioactive form of MTIII. The motif may be observed in yet to be identified metalloregulatory proteins that regulate other processes in a Cu- or Zn-specific manner. Formation of metal:thiolate polymetallic clusters allows a significant volume of the protein structure to be altered, so metal-induced structural dynamics are possible. CuS polynuclear clusters may be more general than the MT motif in biology. The only molecules currently known to form CuS polynuclear clusters include MT, ACE1 and the Cu(gamma EC)nG complexes, although AMT1 and MTIII are expected to be the next members in the list. Three other Cys-rich proteins, papilloma viral E7 and LIM motif-containing CRP and CRIP, isolated as Zn2+ proteins exhibit facile metal exchange in vitro with Cu1+. The resulting Cu1+ proteins show optical properties similar to CuMTs (202,203). Although CuS clusters may form in E7 and LIM-containing proteins, it is premature to ascribe any biological significance to the Cu1+ conformers. PMID- 8203285 TI - Iron and ferritin in inflammation and cancer. PMID- 8203286 TI - The structural and functional roles of calcium ion in secretory phospholipases A2. PMID- 8203287 TI - Selenium biochemistry--selected topics. PMID- 8203288 TI - Artificial proteolysis by a metal chelate: methodology and mechanism. PMID- 8203289 TI - Insights into the structural and electronic properties of metalloproteins by heteronuclear magnetic resonance. PMID- 8203290 TI - Cytochrome P-450 and peroxidase chemistry. PMID- 8203291 TI - Extracellular phosphorylation in Leishmania major and Leishmania mexicana during heat shock transformation. AB - The extracellular phosphorylation of exogenous substrates have been studied in two Leishmania isolates, L. mexicana and L. major, that differ in their capacity to transform from promastigotes to amastigote-like cells when submitted to heat shock condition. When submitted to heat shock both parasites showed an increase in their extracellular phosphorylation activity. L. major promastigotes that do not transform to amastigote-like cells at 37 degrees C, do not phosphorylate exogenous substrate when the culture is grown at 25 degrees C. In contrast, L. mexicana promastigotes, that transform to amastigote-like cells at 37 degrees C, showed a strong phosphorylation at this temperature. As response to heat shock exposure, the extracellular phosphorylation for L. major increases steadily reaching a maximum at 360 min. On the other hand, L. mexicana also show an increase in phosphorylation during transformation, but in this case the maximum was detected after 10 min. The results are discussed in relationship to the capacity of the parasite to survive once inside the vertebrate host. PMID- 8203292 TI - Species composition and inversion polymorphism of the Anopheles gambiae complex in some sites of Ghana, west Africa. AB - Samples of Anopheles gambiae s.1. were collected from eight localities belonging to four of the five main ecological strata of Ghana. Analysis of ovarian polytene chromosomes revealed the presence of A. gambiae s.s. in all the sites studied, while A. arabiensis was detected only in the extreme northern locality of Navrongo and A. melas in some southern sites. Anopheles arabiensis showed a degree of inversion polymorphism comparable to the one observed in other West African countries. The analysis of the chromosomal polymorphism of A. gambiae s.s. showed the presence of the FOREST form in the rain forest localities and the SAVANNA form in the coastal savanna sites. The MOPTI form occurred sympatrically with the SAVANNA form in the northernmost locality. The possible influence of the presence of various taxa of the A. gambiae complex and of their intra-specific variants on malaria vectorial system is discussed. PMID- 8203293 TI - Isolation of Trypanosoma spp. from wild tsetse flies through procyclic expansion in Glossina morsitans centralis. AB - Procyclic trypanosomes from wild tsetse flies were membrane-fed to Glossina morsitans centralis in order to develop an optimal technique for propagating field isolates. A 70% success rate was achieved in isolating Trypanosoma simiae and a variety of genotypes of T. congolense originating from G. pallidipes, G. brevipalpis and G. swynnertoni. Parasites matured into forms infective for mammals, and could be maintained by passage of gut forms to new groups of flies. In experiments with laboratory stocks, we also passaged immature gut infections of T. congolense and T. brucei from various tsetse species to G. m. centralis. The optimal technique was investigated for procyclic T. congolense through addition of various compounds to goat blood using G. m. centralis and G. m. morsitans as recipients. From these experiments, many approaches to procyclic expansion appeared possible. However, a simple and practical method based on the use of fresh goat blood for rapid feeding of G. m. centralis is recommended. Application of this technique should aid in the resolution of questions relating to the cryptic diversity of Nannomonas trypanosomes in diverse host and vector communities. PMID- 8203294 TI - Isometamidium concentrations in the sera of Boran cattle: correlation with prophylaxis against tsetse-transmitted Trypanosoma congolense. AB - Fifteen Boran cattle from a trypanosomiasis-free area were injected intramuscularly with isometamidium chloride at a dose of 1 mg/kg body weight. Thereafter, the cattle were challenged at monthly intervals with Glossina morsitans centralis infected with one of three populations of Trypanosoma congolense (IL 3893, IL 3889 or IL 1180) until all animals became infected. Isometamidium concentrations in the sera of these cattle were measured using a competitive enzyme-linked immunosorbent assay over the first 105 days following treatment. All cattle challenged with IL 3893 or IL 3889 developed infection following the first challenge, at which time the mean serum drug concentration in all treated cattle was 6 ng/ml. Cattle challenged with IL 1180 became infected following 6 to 8 monthly challenges. The mean serum drug concentration in these cattle at the time of their third monthly challenge with IL 1180 was 0.75 ng/ml. Trypanosome populations IL 3893 and IL 3889 were considered to be highly resistant to isometamidium, while IL 1180, relatively sensitive. It was therefore concluded that T. congolense persisting at serum isometamidium concentrations greater than 0.75 ng/ml can be considered moderately resistant, while those persisting at concentrations greater than 6 ng/ml can be considered markedly resistant. These results will be most valuable in the investigation of isometamidium resistance of T. congolense in the field. PMID- 8203295 TI - The in vitro antimalarial activity of chloramphenicol against Plasmodium falciparum. AB - The minimum inhibitory concentrations, MIC, of chloramphenicol were determined for two isolates of Plasmodium falciparum at 48, 96 and 144 h. The MIC decreased from values greater than 100 micrograms/ml at 48 h to 10.7-12.5 micrograms/ml at 96 h. During 144 h of incubation, concentrations of 0.8-1.6 micrograms/ml were effective in suppressing parasite growth. These results indicate that the multiplication of malaria parasites can be inhibited by clinically achievable concentrations of chloramphenicol provided that exposure to the drug is prolonged over several asexual life cycles. They suggest that undiagnosed falciparum infections may be cured when patients with fever of doubtful origin are treated with 10 to 14 day courses of chloramphenicol. They also raise the possibility that this antibiotic may eventually be used, in combination with a rapidly acting but non-curative drug regimen, to treat patients with falciparum infections in whom the use of tetracyclines is contraindicated, e.g., young children. PMID- 8203296 TI - A simple technique to pretreat urine and serum samples for quantitation of schistosome circulating anodic and cathodic antigen. AB - For the detection of the circulating schistosome antigens CAA (circulating anodic antigen) and CCA (circulating cathodic antigen) in serum and urine samples of Schistosoma infected individuals, pretreatment of samples with trichloroacetic acid (TCA) is a standard procedure. In the present study several methods were evaluated in order to develop a more simple and rapid technique than the- especially for pretreatment of urine samples--laborious TCA technique. Optimal results were obtained with a method in which serum or urine samples were pretreated by a heat-incubation step (70 degrees C, 30 min) in an alkaline buffer (pH 9.6). In a comparison of the new technique with the TCA pretreatment, serum and urine samples of S. mansoni infected individuals from Zaire (n = 80) and of uninfected controls from The Netherlands (n = 208) were pretreated and assayed for CAA and CCA. Both pretreatment techniques showed similar sensitivities and specificities for CAA and CCA in serum, and CCA in urine. However, for the determination of CAA in urine the new technique performed significantly better, resulting in an increase of the sensitivity from 32 to 70% (titre determination). PMID- 8203298 TI - Estimation of permissible levels of transmission of bancroftian filariasis based on some entomological and parasitological results of a 5-year vector control programme. AB - The impact of a 5-year vector control programme on transmission of bancroftian filariasis and microfilaraemia levels in the human population was examined in Pondicherry, South India. The programme reduced and maintained the transmission of Wuchereria bancrofti at appreciably low levels in many localities of Pondicherry town, but its impact on overall microfilaraemia prevalence was only limited. However, prevalence of infection was reduced drastically in children born after establishment of the programme and only 18% of the number expected without vector control were found infected. No new infections were found in localities with less transmission intensity. It is proposed that a Transmission Intensity Index of 0.50 and Annual Transmission Potential of less than the 96-105 range are permissible levels of transmission, and below these levels no new infections may occur. The required duration of vector control to eliminate Culex borne filariasis foci is estimated to be 11-12 years, slightly longer than that required to eradicate anopheline-borne filariasis. PMID- 8203297 TI - Screening Tanzanian medicinal plants for antimalarial activity. AB - Forty-three different plant species commonly used in traditional medicine for the treatment of malaria were selected and screened for their antimalarial activity against Plasmodium falciparum in vitro. Thirteen of the 43 species were obtained directly from traditional healers who use these plants for the treatment of malaria. The other plant species were collected on the basis of ethnomedicinal information in the literature. The plant material was collected from Morogoro, Dar es Salaam and Kagera regions in Tanzania. Fifty-eight plant samples from these 43 plant species, including leaves, roots and stem bark, were investigated. Apart from the crude EtOH extracts, petroleum ether (PE), ethyl acetate (EtAc) and H2O fractions of these extracts were also tested. The in vitro testing revealed that 37% of the investigated plants showed strong antimalarial activity with IC50 values below 10 micrograms/ml. The four most active plants included Cissampelos mucronata, Maytenus senegalensis, Salacia madagascariensis and Zanthoxylum chalybeum. PMID- 8203299 TI - Construction of an intrinsic cut-off value for the sero-epidemiological study of Trypanosoma evansi infections in a canine population in Brazil: a new approach towards an unbiased estimation of prevalence. AB - In the serodiagnosis of tropical infectious diseases, cut-off values are often established by using sera from individuals living under moderate climatic conditions, not exposed to the risk of infection (non-endemic controls). This approach guarantees the disease-free status of the individuals within that control group but leads to an assembly of samples which are not representative for the disease-free individuals of the target population (selection bias). Using data from an epidemiological study of Trypanosoma evansi infection in dogs, two alternative methods to construct cut-off values for a T. evansi antibody ELISA are described which are solely based on a distribution analysis of the data from the endemic animals. By cluster analysis these data could be divided into 'high', 'intermediate' and 'low responders'. High responders could also be identified by using the computer-assisted analysis of mixtures (C.A.MAN). Conventional cut-offs were calculated from a group of non-endemic individuals. A receiver operating characteristic (ROC) analysis was performed to demonstrate the impact of the choice of cut-offs on the test specificity and on the estimated seroprevalence among the endemic population. The data indicate that distribution analysis, especially the mixture analysis (C.A.MAN), are valuable tools for the unbiased estimation of seroprevalence when representative negative controls are not available. PMID- 8203300 TI - The disposition of antiparasitic drugs in relation to the development of resistance by parasites of livestock. AB - The kinetic and dynamic disposition of endo- and ectoparasiticides in livestock in relation to development of resistance is examined. Based on the modes of action of antiparasitic drugs, maximum activity necessitates that the parasite be exposed to 'toxic' concentrations for as great a duration as possible. In contrast, exposure to non-lethal discriminating drug concentrations has a significant potential to promote the development of resistance. Orally administered anthelmintics quickly associate with particulate digesta in the rumen; their subsequent desorption from particulate matter as it vacates the rumen maintains the duration of metabolite availability. The flow rate of digesta increases with feed intake and the presence of gastrointestinal parasites, and together with other parasite-induced physiological changes to the gut, contributes to reduced duration of drug availability. The potential for orally administered drugs to bypass the rumen, due to closure of the oesophageal groove, exacerbates the effect. Once absorbed, the metabolite concentration with time profile progressively decreases, the rate depending upon the chemical nature of the drug and the type and condition of the host into which it was administered. The greater hepatic activity of goats speeds drug elimination, the lower dose equivalent availability increases the potential for generation of drug resistance in parasites of goats as compared to sheep. Parasites whose resistance is generated in goats may be then transferred to sheep. Similar distribution/elimination kinetics apply to topically administered insecticides of sheep. The progressively reducing concentrations expose ectoparasites to discriminating drug levels, again contributing to the development of resistance. It is anticipated that a greater understanding of the physiological/pharmacological effects which are described in this review will permit the more efficient use of existing and future antiparasitic drugs. PMID- 8203301 TI - Epidemiology of drug resistance in malaria. AB - In the late 1950's chloroquine resistance to Plasmodium falciparum occurred in South America and on the Indochina Subcontinent. Since then it has conquered most of the areas where the parasite species is endemic. This has necessitated the use of alternative drugs such as sulphonamide-pyrimethamine combinations, quinine/tetracyclines, mefloquine, halofantrine, and recently also artemisinin based compounds. In wide areas of South-east Asia, western Oceania and South America sulphonamide-pyrimethamine combinations have lost adequate efficacy. The situation is most serious in the Thai/Cambodia and Thai/Myanmar border areas where multiresistance necessitated the shift to the last line drug, i.e., the artemisinin derivatives. Selection of resistant parasites due to drug pressure, and their subsequent propagation by local transmission and migration of reservoirs are key factors in the dynamics of drug resistance. Selection is the result of the interplay of parasite, drug and human host, and is largely influenced by immune factors and the pharmacokinetics and pharmacodynamics of the drug. Spread of resistance is determined by eco-epidemiological factors among which migration and vectorial parameters play a major role. Rational drug use, especially adequate, monitored, therapeutic administration according to strict criteria, should curb the onset and spread of resistance, but this concept may not be readily accepted by health services whose primary goal is clinical amelioration of the disease rather than the more stringent target of epidemiologically desirable results. PMID- 8203302 TI - The mode of action and the mechanism of resistance to antimalarial drugs. AB - The mechanism of action of the antifolate and quinoline antimalarials has been investigated over the last few decades, and recent advances should aid the development of new drugs to combat the increasingly refractile parasite. The molecular description of resistance to the antifolates has been well characterised and is due to structural changes in the target enzymes, but the factors involved in the parasite's ability to circumvent the action of the quinoline antimalarials have yet to be fully elucidated. This review discusses the mode of action of these drugs and the means used by the parasite to defeat our therapeutic ingenuity. PMID- 8203303 TI - Resistance to the nitroheterocyclic drugs. AB - The nitroheterocyclic drugs have been available since the early 1960's for the treatment of anaerobic protozoa. The application of these drugs has widened since then and they are presently used to treat anaerobic pathogenic bacteria and protozoa. The activity of the nitroheterocyclic drugs depends on the all important nitro group attached to the imidazole or furan ring. Although the nitro radicals, generated by reduction of the parent drugs, are similar for both families of nitroheterocyclics, the nitroimidazoles and the nitrofurans, the electron potential of each is different and thus the mechanism of action depends on different pathways. The nitroimidazoles depend on reduction by ferredoxin or flavodoxin. The nitrofurans require nitroreductase activity, but the natural substrate of these enzymes has not been identified. Increased use of nitroheterocyclic drugs, in response to drug resistance to other commonly used antibiotics, has in turn resulted in drug resistance to a number of nitroheterocyclic drugs. Bacteroides strains and other bacteria, including Helicobacter, have developed resistance. Among the protozoa, Trichomonas has developed resistance to metronidazole via a number of mechanisms, especially a decrease in drug reduction, as a result of alterations in the electron transport pathways. Resistance to both types of nitroheterocyclic drugs has been reported in Giardia. Although resistance to these drugs is not widespread, their increased use world-wide as a prophylaxis and in chemotherapy will inevitably result in increased resistance in organisms commonly found in asymptomatic infections, including Trichomonas, Giardia and Entamoeba. However, the variety of substitutions which can be attached to the ring structures has led to a great variety of drugs being synthesised, some of which are many-fold more active than the commonly prescribed nitroheterocyclics. With careful administration of currently available drugs and continued interest in synthesising more active compounds, we can optimistically expect to have useful nitroheterocyclic drugs available for some time. PMID- 8203304 TI - Drug resistance to schistosomicides and other anthelmintics of medical significance. AB - It is usual for people to be infected for some period in life with parasitic worms, which may cause morbidity or even kill. Anthelmintics are used for the treatment and control of the human helminthiases, since no vaccines are yet available. Despite the widespread use of these compounds, drug resistance has become apparent only with antischistosomal chemotherapy, in contrast to the situation with other anti-infective agents in human medicine and with veterinary anthelmintics, where resistance is widespread. This paper reviews research on drug resistance in human helminthiasis with emphasis on schistosomicidal drugs. PMID- 8203305 TI - The development of anthelmintic resistance in ruminant livestock. AB - Despite the enormous advances over the last 50 years in the chemotherapeutic control of nematode parasites, the economic importance of these parasites to the grazing livestock industries remains as great as ever. Added to this, the emergence and rapid development of resistance to the new broad spectrum anthelmintics in the important nematode species now looms large as a major international threat. This particularly is of concern to the sheep industry, especially in the major sheep-raising countries of the Southern Hemisphere, but there are clear signs that the problem in Western Europe and North America is rapidly escalating. Resistance is also a serious concern in the intensive goat industry, but at present appears to occur only on isolated, individual cattle properties. To obtain a perspective of the development of anthelmintic resistance in relation to husbandry practices, this review focuses on the problem in the sheep industry in relation to its development, detection and management. PMID- 8203306 TI - Biochemistry of benzimidazole resistance. AB - Heavy reliance on the benzimidazole (BZ) anthelmintics since their introduction in the 1960's for the control of gastrointestinal parasites of livestock has led to widespread BZ resistance in target parasite species. The BZs exert their primary action by binding to tubulin, the major protein component of microtubules. This review discusses the biochemistry of the interaction between the BZs and tubulin from mammalian and BZ-resistant and -susceptible parasite sources, exploring aspects of the selective toxicity of these drugs and examining the mechanism of BZ resistance. Although tubulin is a highly conserved protein present in both the host and the parasite, the BZs demonstrate relatively low mammalian toxicity. The selectivity of these drugs can be explained by the much higher affinity of the BZs for tubulin from the parasite at 37 degrees C compared to their affinity for tubulin from the host. This difference in affinity reflects the considerably slower rate of BZ dissociation from parasite tubulin. BZ resistance in parasitic nematodes is characterised by a loss of high affinity BZ parasite tubulin interactions and a corresponding increase in lower affinity interactions, although there are still significant differences between BZ resistant parasite tubulin and tubulin from the host. These differences suggest the potential for the design of new generation BZs active against 'BZ-resistant' parasites. PMID- 8203307 TI - Ventricular ectopic activity: to treat or not to treat. PMID- 8203308 TI - Ventricular arrhythmias: advice from a family physician. PMID- 8203309 TI - Health care reform and patient-physician communication. PMID- 8203310 TI - The quandary over cholesterol reduction. PMID- 8203312 TI - 'Golden hair syndrome' vs. 'Goldenhar syndrome'. PMID- 8203311 TI - Oral fluoroquinolones for malignant external otitis. PMID- 8203313 TI - Alternative procedure for removal of Norplant. PMID- 8203314 TI - Hypnosis for nausea and vomiting in pregnancy. PMID- 8203315 TI - An ill patient in the office: think adverse drug reaction. PMID- 8203316 TI - Physical and functional assessment of the elderly stroke patient. AB - A functionally oriented approach to acute stroke care should take place in parallel with traditional medical management, since the medical care provided during the first days and weeks after a stroke affects the patient's ultimate disability status. The components of the functionally oriented approach include a comprehensive history and physical examination, through which information is obtained on current disabilities and abilities, risk factors for common poststroke complications, psychologic and social resources, and environmental barriers that preclude maximal functioning. PMID- 8203317 TI - The toddler who does not eat. AB - The majority of children between two and five years of age who are brought in by their parents for refusing to eat are healthy and have an appetite that is appropriate for their age and growth rate. Unrealistic parental expectations may result in unnecessary concern, and inappropriate threats or punishments may aggravate the refusal to eat. A detailed history and general physical examination are necessary to rule out acute and chronic illnesses. A food diary and assessment of parental expectations of eating behavior should be completed. When the child's "refusal to eat" is found to be related to unrealistic parental expectations, the parents should be reassured and counseled about the normal growth and development of children at this age. PMID- 8203318 TI - Management of chronic ventricular arrhythmias. AB - Premature ventricular contractions occurring in asymptomatic patients without heart disease are benign and need not be treated. Beta blockers may be used for symptomatic patients. Antiarrhythmic therapy for patients after myocardial infarction is controversial; authors of recent studies have tended to discourage this therapy. Patients with malignant arrhythmias--who have been resuscitated from cardiac arrest caused by ventricular ectopy or who have ventricular tachycardia-associated syncope--should be referred for electrophysiologic testing and individualized therapy. PMID- 8203319 TI - Anaerobic lung infections. AB - Aspiration is the leading cause of anaerobic lung infections. Risk factors for these infections include a depressed level of consciousness, a history of seizure, general anesthesia, central nervous system or neuromuscular disease, cerebrovascular accident, impaired swallowing and use of a tracheal or nasogastric tube. Clinical presentation includes fever, weight loss, malaise and cough productive of foul-smelling sputum. Diagnosis is based on radiographic findings, clinical features and a characteristic morphology of mixed flora on Gram stain of uncontaminated pulmonary specimens. The diagnosis is confirmed by isolation of organisms, usually polymicrobial, on culture. Treatment includes proper drainage, debridement of necrotic tissue and an antibiotic regimen (often initially empiric) with an agent active against anaerobic and aerobic organisms. PMID- 8203320 TI - Chlamydial cervicitis: complications and new treatment options. AB - Chlamydial cervicitis has the potential for serious gynecologic complications, including pelvic inflammatory disease, infertility and ectopic pregnancy. In the pregnant patient, this infection is associated with premature rupture of membranes and increased fetal morbidity and mortality. In addition, infants infected by passage through an infected cervix are at risk for respiratory complications and conjunctivitis. Chlamydial cervicitis may, however, be asymptomatic, and no single risk factor has been identified that reliably predicts infection. Current recommendations are to screen all pregnant women and patients in high-risk populations, such as those attending clinics for sexually transmitted diseases. Screening tests for chlamydial cervicitis are limited by expense and technical difficulties in obtaining and handling specimens. Chlamydial cervicitis can be treated effectively with several antibiotics, including doxycycline, ofloxacin and erythromycin. Newer antibiotics such as azithromycin offer the potential of effective single-dose treatment. PMID- 8203321 TI - Earlobe keloids. AB - Earlobe keloids are a challenging management problem. These benign, fibrous proliferations develop in predisposed persons at sites of cutaneous injury or as the result of ear piercing, burns or surgical procedures. Earlobe keloids usually appear as shiny, smooth, globular growths on one or both sides of the earlobe. Patients frequently complain of cosmetic embarrassment, but also may report pruritus, pain or paresthesias. No single therapeutic modality is best. The location, size, depth and duration of the earlobe keloid influence the choice of therapy. Surgical treatment for earlobe keloids generally includes core excision with low-tension wound closure, and shave excision. Surgical repair with corticosteroid injections and postoperative pressure on the incision site usually provide good cosmetic results. Patients must be counseled about recurrence, palpable postoperative nodules and the need for close monitoring. PMID- 8203322 TI - Scapholunate dissociation. AB - Scapholunate dissociation is the most frequent serious ligamentous injury of the wrist. Untreated, this injury can lead to disabling wrist pain, reduced wrist mobility and chronic degenerative arthritis. Early recognition of the injury by careful clinical and radiographic examination results in the most favorable prognosis. Standard posteroanterior and lateral radiographs of the wrist may be inadequate. Instead, radiographs obtained with the wrist in radial and ulnar deviation or with the hand gripping forcefully may be needed to reveal the instability of this joint. Magnetic resonance imaging may be required in special cases, as it is the only imaging modality that can directly depict abnormalities of the ligaments. Surgical intervention is recommended for optimal results. Chronic injuries require specialized operative and rehabilitative management. PMID- 8203323 TI - Management of cancer pain: adults. Cancer Pain Guideline Panel. Agency for Health Care Policy and Research. PMID- 8203324 TI - The problem of somatization in family practice. AB - Patients with somatization disorder, in the full-blown or subsyndromal form, are high users of health care and often receive expensive, unnecessary tests and treatments. Their multiple somatic complaints do not have a biomedical basis but, instead, reflect underlying emotional conflicts that the patient is unable to face. Treatment of these patients is difficult, with no approach showing a good cure rate. However, if the underlying psychosocial etiology is understood and modest goals are set, much can be done to limit the problem and reduce symptoms. Management includes setting clear limits on the patient's access to the physician, while maintaining an empathetic and supportive doctor-patient relationship. Behavioral cognitive psychotherapy and short-term intensive psychotherapy may help the patient understand the underlying conflicts and thereby reduce the symptoms. PMID- 8203325 TI - The Mammography Quality Standards Act of 1992. PMID- 8203326 TI - ACP and IDSA issue statement on human immunodeficiency virus infection. PMID- 8203327 TI - ACIP releases new recommendations on immunization. PMID- 8203328 TI - AIDS in heterosexuals. PMID- 8203329 TI - Percutaneous transluminal coronary angioplasty in African-American patients (the National Heart, Lung, and Blood Institute 1985-1986 Percutaneous Transluminal Coronary Angioplasty Registry). AB - Although black patients have a higher prevalence of risk factors for coronary artery disease, the outcome of coronary angioplasty in black patients is not known. The purpose of this study was to determine if any racial differences existed in the clinical characteristics and outcome of patients enrolled in the 1985-1986 National Heart, Lung, and Blood Institute (NHLBI) Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry. The clinical characteristics, in-hospital event rates, and 5-year follow-up results of all patients enrolled in the 1985-1986 NHLBI PTCA Registry were examined with respect to race. Of the patients enrolled in the registry, 1,939 (90.8%) were white and 76 (3.6%) were black. Among black patients there were more women (50% vs 24%, p < 0.001), and more patients who had hypertension (73% vs 45%, p < 0.001) and diabetes (23% vs 13%, p < 0.05). Black patients were more likely to have multivessel disease (72% vs 48%, p < 0.001). Clinical success rates were similar (76.3% for blacks and 79.3% for whites), but because black patients had more vessels with significant disease, complete revascularization was achieved in 26% of black patients compared with 44% of white patients (p < 0.001). After the PTCA procedure there was no significant difference in major complications (death, myocardial infarction, or emergent coronary artery bypass grafting) between the 2 groups. Five-year follow-up data revealed that there was no significant difference in mortality, myocardial infarction, coronary artery bypass grafting, or repeat PTCA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203330 TI - Effect of prior coronary restenosis on the risk of subsequent restenosis after stent placement or directional atherectomy. AB - Lesions that have developed restenosis after a prior intervention may be more likely to develop restenosis after subsequent percutaneous interventions. To determine if this is an independent effect, the clinical characteristics and immediate angiographic outcomes of 179 prior restenosis lesions were compared with those of 254 primary lesions after stenting or directional atherectomy. Six month angiographic follow-up was obtained for 79% of successfully treated lesions. Univariable and multivariable logistic regression was used to determine how binary restenosis (defined as > or = 50% diameter stenosis at follow-up) was influenced by postprocedure luminal diameter, left anterior descending artery location, diabetes mellitus, as well as prior restenosis. At 6-month follow-up, prior restenosis lesions had a significantly smaller late diameter (1.77 vs 2.18 mm, p < 0.001), more absolute late loss (1.35 vs 1.14 mm, p = 0.051), a higher loss index (0.58 vs 0.45, p < 0.02), and a higher binary restenosis rate (37.3% vs 24.4%, p = 0.01). Whereas univariable analysis revealed that left anterior descending artery location, diabetes mellitus, postprocedure luminal diameter < 3.1 mm, and prior restenosis were each strong predictors of binary restenosis (all p < 0.02), multivariable analysis showed that after adjustment for left anterior descending artery location, diabetes, and postprocedure luminal diameter, prior restenosis was no longer an independent predictor of restenosis (odds ratio 1.57, 95% confidence interval 0.95-2.60, p = 0.073). In conclusion, although prior restenosis lesions do show more restenosis than primary lesions, much of this effect is due to preselection of a population enriched in other known factors that predispose to restenosis. PMID- 8203331 TI - Serum lipids and restenosis after successful percutaneous transluminal coronary angioplasty. Ichilov Magnesium Study Group. AB - The effects of plasma lipids on the clinical and angiographic parameters of 134 patients, in whom coronary angioplasty was performed in 157 vessels, were prospectively examined. During a 6-month follow-up, restenosis was detected angiographically in 39 patients (29%; 45 vessels). None of the clinical, biochemical, or angiographic variables examined was predictive of stenosis and the tendency of a vessel to restenose was not patient-dependent but rather lesion related. However, restenosis developed in 31 of 102 vessels (30%) in patients with high-density lipoprotein (HDL) cholesterol < or = 40 mg/dl, compared with restenosis in 10 of 55 vessels (19%) in patients with HDL cholesterol > 40 mg/dl (p = 0.092). No significant differences were observed when restenosis rates were compared in patients with total cholesterol levels > 250 mg/dl or < 250 mg/dl; no differences were seen in low-density lipoprotein (LDL) cholesterol levels when comparing patients with > 160 mg/dl and < 160 mg/dl. In 117 patients (132 vessels), complete serial blood specimens were obtained until the concluding angiography at 6 months. During follow-up, both groups (those with and without restenosis) had almost similar findings. Triglycerides decreased equally in both groups, and total cholesterol increased mildly in those who had restenosis; HDL and LDL cholesterol levels increased significantly in each group. No significant differences were observed with respect to extent of these changes between the groups. Thus, although lipid levels at the time of angioplasty and at 6 months follow-up were not found to predict the occurrence of restenosis, the association of low high-density lipoprotein levels and the tendency for restenosis should not be overlooked. PMID- 8203332 TI - Hemodynamic and metabolic correlates of dipyridamole-induced myocardial thallium 201 perfusion abnormalities in multivessel coronary artery disease. AB - The mechanisms responsible for the development of reversible thallium-201 (TI 201) defects with dipyridamole stress in patients with coronary artery disease (CAD) is not well understood. Previous experimental animal studies have demonstrated coronary steal characterized by an absolute decrease in subendocardial flow distal to a stenosis in response to dipyridamole infusion. Accordingly, the purpose of this study was to determine if reversible TI-201 defects in response to dipyridamole infusion are reflective of myocardial ischemia or secondary to regional differences in flow reserve. Dipyridamole (0.56 mg/kg) TI-201 imaging was performed in 23 patients in whom serial electrocardiographic, hemodynamic, aortic and coronary sinus lactate, and coronary sinus adenosine measurements were obtained. All patients with CAD had TI 201 redistribution (3.8 +/- 2.0 defects/patient), and all patients without CAD had normal scans. Mean aortic pressure was similar in both groups and did not change in response to dipyridamole (non-CAD 103 +/- 11 vs CAD 99 +/- 15 mm Hg, p = NS). Pulmonary capillary wedge pressure was similar at baseline (non-CAD 11 +/- 4 vs CAD 13 +/- 5 mm Hg, p = NS) and did not change in response to the drug (non CAD 14 +/- 3 vs CAD 15 +/- 7 mm Hg, p = NS). Lactate extraction fraction was similar at baseline (non-CAD 0.22 +/- 0.09 vs CAD 0.17 +/- 0.14, p = NS) and decreased similarly in both groups (non-CAD 0.08 +/- 0.06 vs CAD 0.05 +/- 0.12, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203333 TI - Relation of coronary calcium determined by electron beam computed tomography and lumen narrowing determined by autopsy. AB - Coronary calcium determined by electron beam computed tomography (CT) has not been systematically evaluated regarding prediction of histopathologic atherosclerotic disease. Furthermore, gender specificity has not been examined. The 3 major epicardial arteries were dissected from 13 consecutive hearts (5 women and 8 men) after autopsy. Each artery was straightened and scanned using CT in contiguous 3 mm thick cross sections. After imaging, histologic sections were prepared at corresponding intervals and luminal area obstruction determined by planimetry. Electron beam CT scans were analyzed to determine coronary calcium area (i.e., tomographic area with CT density > 130 Hounsfield units). A total of 522 histologic specimens were examined and paired with corresponding CT scans (182 in women, 340 in men). Receiver-operating characteristic (ROC) analysis was used to define site specificity of calcium area for luminal area narrowing by atherosclerosis. ROC curve areas for segmental CT calcium and prediction of atherosclerosis representing mild, moderate, or severe disease were, respectively, 0.712, 0.843, and 0.857 for women and 0.732, 0.793, and 0.841 for men. Curves relating false-positive rate (1-specificity) to predefined degrees of atherosclerotic narrowing versus calcium area were curvilinear. In both women and men, calcium areas on the order of 1 mm2/coronary segment were necessary to predict at least mild atherosclerosis with a false-positive rate of 0% (i.e., 100% specificity), whereas a calcium area > 3 mm2 was necessary to predict the same result for severe disease. In conclusion, coronary artery calcium area as determined by electron beam CT has the potential to predict segmental histopathologic coronary disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203334 TI - Abnormal autonomic control of the cardiovascular system in syndrome X. AB - Anomalies of autonomic control of the coronary circulation may play a role in the development of syndrome X (angina pectoris, ischemic-appearing results on exercise test, and normal coronary arteriograms). Twenty-six patients with syndrome X and 20 healthy sex- and age-matched control subjects were studied by means of analysis of heart rate variability during 24-hour Holter monitoring. Spectral and nonspectral parameters of heart rate variability were investigated. Mean heart rate was similar in patients with syndrome X and in control subjects. Patients with syndrome X had significantly lower standard deviation of all normal RR intervals, a lower percentage of adjacent normal RR intervals > 50 ms in difference (126.4 +/- 22 vs 149 +/- 43 ms, p < 0.05; 6.3 +/- 4 vs 11.2 +/- 7%, p < 0.05; respectively), and a trend toward lower values of time-domain parameters. Lower values of total power and low frequency were also observed in patients with syndrome X (1273 +/- 693 vs 1790 +/- 989 ms2, p < 0.05; 406 +/- 176 vs 729 +/- 455 ms2, p < 0.01, respectively). An inverse correlation between heart rate and measures of heart rate variability was found in syndrome X but not in control subjects. High- and low-frequency power showed a similar circadian pattern in syndrome X patients and control subjects. Patients and control subjects were then allocated into 2 groups according to the median RR duration: syndrome X1 and control 1 with high mean heart rate, and syndrome X2 and control 2 with low mean heart rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203336 TI - Close relation between lipoprotein (a) levels and atherothrombotic disease in Japanese subjects > 75 years of age. AB - Levels of lipoprotein (a) (Lp[a]) and various hemostatic factors were studied in 132 Japanese aged > 75 years (mean 83). The group consisted of 50 healthy persons, 36 hypertensive subjects, 31 patients with chronic cerebral infarction, and 15 with coronary artery disease. Lp(a) levels were slightly lower in the healthy "old old" subjects than in the 184 healthy younger adults (mean +/- SD: 10.7 +/- 7.9 vs 12.1 +/- 10.1 mg/dl). There were no gender-related differences in the Lp(a) levels of healthy adults and healthy old old subjects. Lp(a) levels were higher in the hypertensive old old subjects (14.6 +/- 15.4 mg/dl) and the old old patients with cerebral infarction (21.3 +/- 16.2 mg/dl) and coronary artery disease (26.5 +/- 20.4 mg/dl). The prevalence of subjects with high Lp(a) levels (> 30 mg/dl) was the greatest among old old patients with coronary artery disease (27%). Lp(a) levels in the 132 old old subjects showed positive correlations with sialic acid, fibrinogen, factor VII activity, and D-dimer levels. These results indicate a close association between Lp(a) levels and atherothrombotic disease as well as the characteristics of Lp(a) as an acute phase reactant in old old Japanese. Subjects with higher Lp(a) levels may develop cardiovascular disease later in life, whereas the remaining healthy old old subjects have lower Lp(a) levels. PMID- 8203335 TI - Comparison of enalapril versus captopril on left ventricular function and survival three months after acute myocardial infarction (the "PRACTICAL" study). AB - Left ventricular (LV) function and survival can be improved with captopril when initiated later than 24 hours after acute myocardial infarction. Animal studies suggest additional benefits may be obtained with earlier initiation of angiotensin-converting enzyme (ACE) inhibitors. The effects on LV function of captopril and enalapril initiated within 24 hours of myocardial infarction were studied. Two hundred twenty-five patients with acute myocardial infarction were enrolled within 24 hours of the onset of chest pain. They were randomized to receive either captopril 25 mg three times daily, enalapril 5 mg three times daily, or placebo. LV ejection fraction (EF) and volumes were measured by radionuclide ventriculography at baseline during treatment and at 3 months after a 3-day withdrawal from therapy. The ACE inhibitor group had a significant increase in EF (45 +/- 1 to 47 +/- 1%; p = 0.005) and significantly attenuated LV dilatation compared with results in the placebo group (175 +/- 6 to 189 +/- 7 ml in the placebo group vs 168 +/- 4 to 172 +/- 4 ml in the ACE inhibitor group; p = 0.051 for LV end-diastolic volume; and 99 +/- 6 to 108 +/- 7 ml in the placebo group vs 94 +/- 3 to 94 +/- 4 ml; p = 0.026 for LV end-systolic volume). The beneficial effects of ACE inhibitor therapy on LV function were observed irrespective of the degree of initial LV dysfunction and were comparable in both the captopril and enalapril groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203337 TI - Determinants of the initial effects of captopril on blood pressure, glomerular filtration rate, and natriuresis in mild-to-moderate chronic congestive heart failure secondary to coronary artery disease. AB - Whereas angiotensin-converting enzyme inhibitors are now indicated for all grades of chronic heart failure, the 2 adverse effects that limit use of these drugs are systemic hypotension and renal dysfunction. The recognized clinical correlates such as hyponatremia and high diuretic dose, which predict occurrence of these adverse effects in severe chronic congestive heart failure (CHF), are rarely evident in patients with mild-to-moderate CHF. Accordingly, we studied 36 patients with stable, moderate CHF in a double-blind, placebo-controlled, crossover fashion to evaluate by multiple discriminate regression analysis the pathophysiologic determinants of changes in blood pressure, glomerular filtration rate, and urinary sodium excretion after initial converting enzyme inhibition with captopril 25 mg. A captopril-mediated decrease in mean arterial pressure was predicted by 3 factors (r2 = 0.74): the decrease in serum angiotensin II (F ratio = 10.3, p < 0.01), the decrease in plasma norepinephrine (F = 8, p = 0.02), and, inversely by pretreatment mean arterial pressure (F = 5.6, p = 0.04), patients with higher initial values exhibiting greater decreases in response to captopril. A captopril-mediated decline in glomerular filtration rate, determined by radioisotope elimination, was also predicted by 3 factors (r2 = 0.67): a decrease in renal plasma flow (F = 48.6, p < 0.01), low pretreatment glomerular filtration rate (F = 11.1, p < 0.01), and low absolute post-treatment serum angiotensin II (F = 5, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203338 TI - Quantitative assessment of valvular function after cardiac transplantation by pulsed Doppler echocardiography. AB - In 31 patients who had undergone cardiac orthotopic transplantation, valvular regurgitation was studied by echocardiographic and pulsed Doppler over 2 years. The first week after cardiac transplantation, transplant recipients had an increase in the severity of tricuspid, mitral (group II), and aortic regurgitation, as well as a greater number of simultaneously regurgitating valves when compared with those in a group of 60 normal subjects of similar age to heart donors: transplant recipients, trivalvular regurgitation 48% (95% confidence interval [CI] 30 to 66) vs control group, 5% (CI 1 to 13; p < 0.001). Moderate severe tricuspid regurgitation (TR) was the most frequent occurrence (55%, CI 36 to 73) followed by pulmonary (PR) (42%, CI 25 to 61), moderate mitral (MR) (32%, CI 15 to 51), and mild aortic (AR) (23%, CI 10 to 43) regurgitation. These regurgitations were asymptomatic at rest except for TR. TR was associated with right-sided heart failure in 76% of patients in the early postoperative period and controlled with diuretic drugs. This regurgitation correlated with persistence of post-transplant pulmonary hypertension (r = 0.6) and was not related to pulmonary hypertension before cardiac transplant. There was also no relation found between donor ischemia time or episodes of cardiac rejection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203339 TI - Left ventricular systolic function in middle-aged patients with diabetes mellitus. AB - In cross-sectional studies of asymptomatic diabetic patients, multiple abnormalities in left ventricular (LV) function have been found. Long-term significance of these abnormalities is unknown because follow-up studies have not been previously performed. LV ejection fraction (EF) by radionuclide angiocardiography was examined in middle-aged control subjects (n = 44), in patients with insulin-dependent (IDDM) (n = 32) and non-insulin-dependent (NIDDM) (n = 32) diabetes mellitus at baseline and after 4-year follow-up. At baseline, all study subjects were free from cardiovascular disease. LVEF at rest did not differ between the groups at baseline. The decrease in LVEF at rest during follow up was 1.1 +/- 1.1% (mean +/- SEM) in control subjects, 3.1 +/- 1.3% (p = NS, compared with control subjects) in patients with IDDM, and 7.2 +/- 1.4% (p < 0.01) in patients with NIDDM. At follow-up examination, abnormally low LVEF at rest (< 50%) was found in 7% of control subjects, 13% of patients with IDDM (p = NS), and in 31% of patients with NIDDM (p < 0.05). Compared with control subjects, the prevalence of an abnormal LVEF response to exercise (an increase by < 5%, or a decrease) was higher in diabetic groups at both examinations. This prevalence increased in control subjects from 10% at baseline to 26% at follow-up examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203340 TI - Evolution of the exercise electrocardiogram. PMID- 8203341 TI - Implantable cardioverter-defibrillators: not the ultimate gold standard for gauging therapy of VT/fibrillation. PMID- 8203342 TI - Complications of percutaneous transluminal coronary angioplasty in patients convalescing from acute myocardial infarction. PMID- 8203343 TI - Predictors of thrombotic complications after placement of the flexible coil stent. PMID- 8203344 TI - Successful use of education and cost-based feedback strategies to reduce physician utilization of low-osmolality contrast agents in the cardiac catheterization laboratory. PMID- 8203345 TI - Effectiveness of coronary stenting for the treatment of chronic total occlusion in angina pectoris. PMID- 8203346 TI - Acute and long-term outcome of failed percutaneous transluminal coronary angioplasty treated by directional coronary atherectomy. PMID- 8203347 TI - Magnesium therapy in new-onset atrial fibrillation. PMID- 8203348 TI - Amlodipine--once-daily monotherapy in systemic hypertension. PMID- 8203349 TI - Diagnostic value of electrocardiography and echocardiography for white coat hypertension in the elderly. PMID- 8203350 TI - Asplenia syndrome--risk factors for early unfavorable outcome. PMID- 8203351 TI - Interacting within metaphors. AB - Creating metaphorical settings in which a patient may therapeutically interact while hypnotized would appear to have many of the advantages of more traditional uses of metaphors and to possess advantages of its own. Although this type of guided imagery may be widely used in practice, it is underrepresented in the literature compared to other uses of metaphor. I describe the use of a castle setting as one example of this type of metaphorical setting that may be useful in working with trauma patients. I also describe some features useful for this interventions, using three case examples. PMID- 8203352 TI - The (limited) possibilities of hypnotherapy in the treatment of obesity. AB - In this paper we review the possibilities and limitations of hypnotherapeutic techniques in the treatment of obesity. In spite of some promising reports, the findings and opinions about the effectiveness of hypnosis in the treatment of obesity vary greatly. We provide a brief overview of specific hypnotherapeutic techniques--such as teaching relaxation, increasing self-control, encouraging physical exercise, altering self-esteem and body image, strengthening motivation, and exploring ambivalence for change--that can be involved in a multidimensional approach to obesity. Case reports illustrate the use of these techniques. PMID- 8203353 TI - Is differential item difficulty specific to hypnosis? AB - Previous hypnosis studies obtaining retrospective depth reports (e.g., Perry & Laurence, 1980) or retrospective realness reports (e.g., Page & Handley, 1992) have found a "parallel nonoverlapping" pattern between mean depth or realness and susceptibility scale items for high- through low-susceptible subjects. To determine if such a pattern, as well as differential item difficulty in general, is specific to hypnosis, 98 undergraduates were administered the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A) of Shor and Orne (1962) as a "test of visual and motor imagination," omitting the eye-closure induction (item #2). A pattern similar to other studies that employed hypnosis was produced. While supporting attribution theory (Bowers, 1973), results also indicate that differences in item difficulty are not specific to hypnosis, but instead are related more broadly to imagination. PMID- 8203354 TI - Dissociative states and disordered eating. AB - To investigate the relationship between eating problems and dissociation, 142 college women completed the Eating Disorders Inventory, the Bulimia Test, the Dissociative Experiences Scale, the Perceptual Alteration Scale, and a demographic information worksheet. The two eating-disorder inventories were strongly correlated (rs = .71). The two dissociation scales, however, were only moderately correlated (rs = .32), suggesting they are measuring different underlying experiences. The pattern of the correlations of the subscales of the dissociation scales with the eating disorder scales suggested that cognitive distortions were not as important in the relationship with eating disorders (all correlations were less than .21) as were dissociation of feelings and loss of control (the correlations for eating related subscales ranged as high as .51). These results were interpreted to suggest that dissociation of feelings might underlie eating problems. These results indicate the value of the use of hypnotherapy in working with eating-disordered clients. PMID- 8203355 TI - Understanding change: five-year follow-up of brief hypnotic treatment of chronic bruxism. AB - In this paper I describe the treatment of a 63-year-old woman with a 60-year history of nocturnal bruxism. Treatment included assessment, two psychotherapy sessions, including a paradoxical behavior prescription to reduce daytime worrying, hypnotic suggestions for control of nocturnal grinding, and reinforcement of the patient's expectations for success. This case demonstrates how enduring change may occur rapidly in spite of the chronicity of a patient's complaint. Follow-up assessments at 2, 3, and 5 years revealed that she continued to be symptom-free with her self-reports corroborated by her spouse and family dentist. I discuss implications for understanding the role of hypnosis in therapeutic change. PMID- 8203356 TI - The effects of self-hypnosis for children with cystic fibrosis: a pilot study. AB - This pilot study assessed the effects of self-hypnosis on psychological and physiological functioning of children ages 7 to 18 with Cystic Fibrosis (N = 12). The study used a pre- and posttest design, repeated measures, and control group. Control and experimental groups were matched for age and clinical severity. The experimental group demonstrated significant changes in locus of control, health locus of control, and self-concept. State anxiety scores did not differ significantly, but changes in trait anxiety distinguished the experimental group from the control group. The experimental group also demonstrated significant increase in peak expiratory flow rates using an air flow meter immediately after self-hypnosis when compared to the control group. Generalizability of the results is discussed in terms of the small sample size. Recommendations are offered for future studies with larger samples and variations in procedure. PMID- 8203357 TI - Primary focal segmental glomerulosclerosis: clinical course and response to therapy. AB - Primary focal segmental glomerulosclerosis (FSGS) is a lesion associated with a poor prognosis and results in end-stage renal disease after 5 to 10 years. Based on past experience, many nephrologists have considered primary FSGS a lesion that is steroid resistant and therefore are reluctant to offer steroids as treatment. Recent data, however, have demonstrated that patients with primary FSGS have a response to steroid therapy that is considerably better than had been described. Thus, it may be that nephrologists have been more "steroid reluctant" than the lesion is steroid resistant. To better understand this issue we review the clinical course and response to therapy in patients with primary FSGS. PMID- 8203358 TI - Renal stone risk factors in patients with type IV renal tubular acidosis. AB - Renal stone formation is uncommon in patients with type IV renal tubular acidosis (RTA). This study was undertaken to explore the urinary biochemical and physicochemical factors in patients with type IV RTA in order to elucidate the mechanisms that protect them from renal stone formation. Twelve subjects with type IV RTA and 12 matched subjects with a similar degree of kidney impairment but without RTA were studied. Both groups of patients had low urinary excretion of calcium, phosphorus, uric acid, and citrate, probably reflective of kidney impairment. Patients with type IV RTA had a significantly lower urinary pH and urinary excretion of calcium than their matched controls. Hypocitraturia was present in both groups without any significant difference between them. This study suggests that the major protection from renal stone formation in type IV RTA results from impaired renal function and ensuing reduction in renal excretion of stone-forming substances, such as calcium and uric acid. PMID- 8203359 TI - Glomerular and tubular factors in urine flow rates of acute renal failure patients. AB - Distinguishing between oliguric and nonoliguric acute renal failure (ARF) has clinical relevance. However, there is a paucity of data regarding the pathophysiologic basis for variations in urine flow rates in ARF. This study was designed to determine whether differences in residual levels of glomerular filtration rate (GFR) or differences in tubular reabsorption of filtered solutes and H2O accounted for the variations in urine flow rates among ARF patients. Twenty-five patients with ARF of 3 to 6 days duration having ischemic and nephrotoxic etiologies, increasing serum creatinines of more than 0.7 mg/dL/d, urine sodium concentrations and fractional excretions of sodium (FENa) of more than 20 mEq/L and more than 1%, respectively, 12 hours after stopping diuretics and urine sediments consistent with acute tubular necrosis were studied. Urine and serum collections were made over an 8-hour period to determine creatinine clearance (Ccr), filtered osmolar load, urine to serum creatinine ratio (U/Scr), urine to serum creatinine osmolality (U/Sosm), and FENa. These were compared with urine flow rates. Creatinine clearance was validated as an estimate of GFR in ARF with simultaneous inulin clearances x 12 measurements (r = 0.935, P < 0.001). Residual Ccr was strongly correlated with urine flow rate (r = 0.857, P < 0.001), as was filtered osmolar load (r = 0.810, P < 0.001). However, the latter relationship was totally dependent on Ccr. There was no correlation between U/Scr, U/Sosm, or FENa and urine flow rates. It is concluded that the residual level of GFR is the primary determinant of variations in urine flow rate in patients with ARF. PMID- 8203360 TI - Antiglomerular basement membrane disease: the long-term pulmonary outcome. AB - We have evaluated long-term pulmonary function in 14 patients who were treated for anti-glomerular basement membrane disease at our institution during the last 17 years. Eight of these patients had evidence of pulmonary involvement, as manifested by hemoptysis, pulmonary infiltrates on chest x-ray film, or anemia. These patients were compared with a control group of 15 patients who had renal disease and who were matched for degree and duration of renal disease, age, smoking history, and method of renal replacement. The following variables were measured in each patient: forced vital capacity, forced expiratory volume in 1 minute, vital capacity, total lung capacity, residual volume, functional residual capacity, single-breath carbon monoxide transfer factor, and single-breath carbon monoxide transfer factor corrected for alveolar volume (KCO). These patients also participated in a graded exercise test and measurements of oxygen uptake, carbon dioxide production, minute ventilation, and oxygen saturation were taken. Patients with anti-glomerular basement membrane disease and a prior history of pulmonary hemorrhage had a significantly reduced KCO (46% +/- 10% v 68.7% +/- 14.7%) compared with the control group. There was no difference in any of the other measured parameters. PMID- 8203361 TI - HLA associations in end-stage renal disease due to membranous glomerulonephritis: HLA-DR3 associations with progressive renal injury. Southeastern Organ Procurement Foundation. AB - Membranous glomerulonephritis (MGN) is the most common cause of idiopathic glomerulonephritis in American adults. African-Americans develop end-stage renal disease (ESRD) due to chronic glomerulonephritis four times more often than whites. To determine whether HLA phenotype associations existed in the subset of MGN patients with ESRD we analyzed HLA frequencies, by race, in patients with MGN entered in the Southeastern Organ Procurement Foundation registry between 1982 and 1992. HLA frequencies from 250 renal transplant patients with MGN (190 whites and 60 African-Americans) were compared with 4,506 race-matched cadaveric kidney donor controls (4,039 whites and 467 African-Americans). Race-specific odds ratios (ORs) were calculated and fitted into a log-linear model to determine associations between MGN and HLA frequencies. The reported values were considered significant (P < 0.05) after Bonferroni correction for multiple comparisons. HLA DR3 and HLA-DR5 frequencies were increased in cases of both races compared with race-matched controls (race-combined ORs, 2.22 and 1.61, respectively; all P < 0.02). Interracial analyses revealed that HLA-DR7 frequency was decreased solely in whites with MGN (OR, 0.53; P < 0.04). The results of this study indicate that HLA-DR3 and HLA-DR5 are positively associated with ESRD due to MGN in patients of both races and that HLA-DR7 is negatively associated with MGN in whites. These analyses confirm the published reports of HLA-DR3 association with MGN in Chinese, French, British, Chilean, and American white populations. The novel association of HLA-DR5 may reflect the fact that the MGN cases in this study all had ESRD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203362 TI - Survival among Mexican-Americans, non-Hispanic whites, and African-Americans with end-stage renal disease: the emergence of a minority pattern of increased incidence and prolonged survival. AB - We undertook this study to determine whether there is a significant difference in survival on treatment for end-stage renal disease between Mexican-Americans, non Hispanic whites, and African-Americans. A database covering the years 1975 to 1986 was obtained from the Texas Kidney Health Program. Eight-eight percent to 90% of patients starting renal replacement therapy in Texas were included in this database. The patients were followed until death, for 3 years after successful transplantation, or until they were lost to follow-up. Life table analysis as well as age-adjusted analysis using the Cox proportional hazards model were performed comparing ethnic/racial groups, disease etiology, and treatment type. In life-table analyses, African-Americans and Mexican-Americans had a survival advantage in most age, disease, and treatment groups. With age adjustment, this survival advantage remained for all etiologies combined, for diabetes and hypertension cases, and for patients receiving hemodialysis in a center. Multivariate analysis revealed a persistent survival advantage for Mexican Americans independent of traditional predictor variables, such as age, disease etiology, treatment type, or size of the center in which they received treatment. In this same analysis, African-Americans showed an advantage in the older age groups. Both African-Americans and Mexican-Americans on renal replacement therapy have an increased survival advantage compared with non-Hispanic whites. Given the additional burden of increased incidence of end-stage renal disease in these groups, the cost of renal replacement therapy for these minorities is disproportionately high. Further study should be aimed at elucidation of the mechanisms by which minorities achieve their survival advantage. PMID- 8203363 TI - Effect of intradialytic parenteral nutrition on mortality rates in end-stage renal disease care. AB - Several studies have now demonstrated that low serum albumin and/or low protein catabolic rates correlate with increased risk of death in the chronic hemodialysis patient. A study involving 81 patients receiving thrice-weekly hemodialysis treatments and who had either a low serum albumin and/or protein catabolic rate was conducted to compare the effect of intradialytic parenteral nutrition (IDPN) on mortality rates. Fifty patients received IDPN and 31 patients did not. Thirty-eight of the patients were black (47%), 34 were white (42%), and 9 were Hispanic (11%). The study included 33 diabetic patients (41%), 20 of whom received IDPN. Nondiabetic patients received an average of 725 kcal/hemodialysis treatment and diabetic patients received an average of 670 kcal/hemodialysis treatment. The average length of treatment was 9 months. The results of the study revealed a better survival rate (64% v 52%) for patients treated with IDPN. Using Cox analysis, the IDPN-treated group had a significantly better survival rate (P < 0.01). Serum albumin increased by 12% in the survivors. There was no difference in survival when considered separately for diabetic and nondiabetic patients who received IDPN (mortality rate for diabetics: 50% for treated patients and 54% for untreated patients; mortality rate for nondiabetics: 26% for treated patients and 44% for untreated patients). However, the nondiabetic treated patients had the lowest mortality rates. In conclusion, correction of hypoalbuminemia by IDPN significantly reduced mortality rates overall. PMID- 8203364 TI - Therapeutic plasma exchange: complications and management. AB - Therapeutic plasma exchange is a treatment modality used in a variety of disease states, some of which are characterized by renal involvement (ie, Goodpasture's syndrome, multiple myeloma, cryoglobulinemia, and thrombotic thrombocytopenic purpura). To investigate the safety of this procedure we evaluated all patients receiving plasma-pheresis at the University of Connecticut from January 1988 to June 1991. Sixty-eight adverse reactions occurred in 699 treatments, resulting in an incidence of 9.7%. The most frequent complications were symptoms of hypocalcemia, hypovolemia, and anaphylactoid reactions. The incidence of hypocalcemic symptoms was lowered with the prophylactic administration of calcium. Without calcium prophylaxis the incidence of symptoms was 9.1% (six in 66 treatments), whereas with calcium prophylaxis the incidence was reduced to 1% (six in 633 treatments) (P < 0.01). Treatments in which albumin was administered as volume replacement were associated with fewer adverse reactions when compared with those using fresh-frozen plasma (1.4% v 20%). Our experience, combined with the 15,658 procedures reported in the literature, reveals that serious complications do not commonly occur. These are characterized by cardiovascular events (0.2%), respiratory events (0.2%), and anaphylactoid reactions (0.25%). Hemorrhage and infection are rare, each occurring at a rate of 0.02%. Death was reported in eight of 15,658 procedures (0.05%). We conclude that therapeutic plasma exchange is relatively safe and alterations in plasma proteins generally are well tolerated. Prophylactic calcium administration lowers the incidence of hypocalcemic symptoms. Adverse reactions are associated more commonly with the administration of fresh-frozen plasma. PMID- 8203365 TI - Blood coagulation, fibrinolytic, and inhibitory proteins in end-stage renal disease: effect of hemodialysis. AB - Patients with end-stage renal disease (ESRD) are at risk of ischemic cardiovascular complications and vascular thrombosis. These observations prompted the present survey of the blood coagulation, fibrinolytic, and inhibitory proteins in a group of 31 ESRD patients and 32 normal controls. Immunologic and functional assays were used to quantitate plasma antigen concentrations and/or functional activities of factors XII, XI, IX, VIII, VII, X, II, and XIII, von Willebrand factor, fibrinogen, fibronectin, high molecular weight kininogen, D dimer, antithrombin III, protein C, protein S, plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor, alpha 2-antiplasmin, alpha 1-antitrypsin, and alpha 2-macroglobulin as well as antiplasmin activity. The coagulant activities of factors XII, IX, X, and II were significantly reduced in ESRD patients despite their normal or increased plasma antigen concentrations. In addition, the ESRD patients showed hyperfibrinogenemia and significant elevations of plasma concentrations of D-dimer, von Willebrand factor, factor VII, and factor XIII antigens. They also exhibited significant reductions of antithrombin III, free protein S, plasminogen, and tissue-type plasminogen activator concentrations. Despite ultrafiltration, plasma factor IX activity and von Willebrand factor and fibrinogen concentrations decreased after hemodialysis with little or slight changes in other measured parameters. The ESRD patients studied here exhibited numerous abnormalities of coagulation, fibrinolytic, and inhibitory proteins at multiple levels. These abnormalities may be involved in the pathogenesis of cardiovascular complications and vascular thrombosis in this population. The precise mechanism(s) and clinical significance of the observed abnormalities are unknown and await further investigation. PMID- 8203366 TI - Advance prediction of early death in patients starting maintenance dialysis. AB - Accurate information on short-term prognosis is needed to help patients, their doctors, and society to make appropriate decisions concerning starting dialysis. We sought to develop a clinically applicable prognostic scoring system to aid in the prediction of death within 6 months of starting maintenance dialysis. Factors potentially predictive of early death were examined retrospectively in an inception cohort of all 325 patients starting dialysis for irreversible renal failure between 1980 and 1991 at a single tertiary care center. The overall mortality rate was 22% at 6 months. Age, cardiac failure, ischemic heart disease, dysrhythmia requiring therapy, severe peripheral vascular disease, advanced neoplasia, ventilator dependency, coma, systemic sepsis, and hepatic failure were independent, significant, prognostic indicators for early death. Multivariate models were used to suggest weights for these variables in a simplified scoring system. Patients with scores < or = 4 (N = 201) had a 6-month mortality rate of 4%, whereas those with a score higher than 9 (N = 21) had a 6-month mortality rate of 100%. Thus, when age and multiple comorbid illnesses were taken into account, it was possible to identify with 100% accuracy 29% of the patients who died within 6 months of starting maintenance dialysis therapy, accounting for 6.5% of the cohort studied. A larger prospective study is warranted to validate this scoring system. PMID- 8203367 TI - Recirculation reassessed: the impact of blood flow rate and the low-flow method reevaluated. AB - The recognition that during hemodialysis the blood urea nitrogen level in a peripheral vein differs substantially from that in an artery has made invalid the conclusions of prior studies based on the standard (peripheral vein) means of calculating recirculation. The increase in recirculation associated with an increase in blood flow may be artifactual, as may the reported inaccuracy of the two-needle low blood flow technique for measuring recirculation. Using a stop flow technique to measure recirculation, a study was performed to reassess these issues. Sixteen patients were each studied once within the first 30 minutes of a standard hemodialysis session (mean, 3.78 hour) at routine blood flow (mean, 419 mL/min) and at 200 mL/min. Dialyzer afferent and efferent blood line samples were obtained, as were afferent samples after sequential, rapid reductions in blood flow to 200, 50, and 0 mL/min. The final two samples were obtained within 30 seconds of reducing blood flow to less than 200 mL/min. Blood flow had a significant (P = 0.03) although clinically minor effect on recirculation (mean, 13.9% at 419 mL/min v 10.2% at 200 mL/min). The low blood flow technique yielded the same results as the stop flow technique (stop flow technique 13.9% v low blood flow technique 13.2% at 419 mL/min, P = 0.76). We conclude (1) that the increase in recirculation associated with increased blood flow is substantially less than has been reported previously and is minimal in a well-functioning access, and (2) that a modified low blood flow (50 mL/min) technique for measuring recirculation yields results equivalent to those obtained using the stop flow technique. PMID- 8203368 TI - Use of intradialytic parenteral nutrition in hemodialysis patients. PMID- 8203369 TI - Crystalline inclusions in the glomerular podocytes in a patient with benign monoclonal gammopathy and focal segmental glomerulosclerosis. AB - We report a case of a 40-year-old woman with benign monoclonal gammopathy who developed focal segmental glomerulosclerosis associated with widespread deposition of large crystalline inclusions in the glomerular podocytes. Electron microscopy showed that the crystalline structures were electron dense and needle shaped or polygonal. At a higher magnification, they were seen to be surrounded by unit membranes and to feature a longitudinal filamentous substructure. These inclusions showed positive immunohistochemical staining for kappa light chain. Clinically, the patient had shown nephrotic syndrome on the first medical examination, and later revealed chronic renal failure and monoclonal gammopathy of the immunoglobulin G kappa type, but no evidence of multiple myeloma or other lymphoproliferative diseases. This patient seems to have had a rare form of glomerular involvement associated with benign monoclonal gammopathy. PMID- 8203370 TI - Multiple manifestations of renovascular hypertension. AB - We report a case of hyponatremia, polyuria-polydipsia, hypokalemia, nephrotic syndrome, and hypertension caused by unilateral renal ischemia, and the resolution after nephrectomy of the ischemic kidney. The renin-angiotensin aldosterone axis seems to play an essential role in the pathogenesis of these features. Mechanisms by which angiotensin II, hypokalemia, and proteinuria can affect salt and water balances, and the role of angiotensin II as a cause of heavy proteinuria are discussed. Renovascular hypertension should be considered in the differential diagnosis of hyponatremia, hypokalemia, and polyuria polydipsia. PMID- 8203371 TI - Accelerated hypertension with encephalopathy due to an isolated dissection of a renal artery branch vessel. AB - Typical causes of renovascular hypertension include intramural atherosclerotic lesions of the main renal arteries or their branches and fibromuscular dysplasia of the renal arterial wall with luminal narrowing. We report a patient with new onset, accelerated hypertension (blood pressure 220/140 mm Hg, status epilepticus, retinal hemorrhages) secondary to a dissection of the anterior division of the right renal artery that was accompanied by hyperreninemia, hyperaldosteronism, and hypokalemia. At presentation in the untreated state, unstimulated plasma renin activity and the serum aldosterone level were markedly elevated. Following right nephrectomy, blood pressure levels normalized without antihypertensive therapy, and plasma renin activity, serum aldosterone and potassium levels normalized. Histologic study of the right renal artery showed an isolated dissection of the anterior branch of the vessel between the muscularis and adventitia that created marked reduction in luminal diameter and renal ischemia. There was no evidence of any other vascular abnormalities, atherosclerosis, or fibromuscular dysplasia. These findings demonstrate that an isolated dissection of a branch of the renal artery may induce profound hyperreninemia and represents a rare, reversible etiology for accelerated hypertension associated with acute encephalopathy. PMID- 8203372 TI - Azathioprine hypersensitivity mimicking Goodpasture's syndrome. AB - Side effects due to azathioprine (the nitroimidazole derivative of 6 mercaptopurine) can be classified as toxic (myelosuppression, hepatotoxicity) and idiosyncratic (fever, rigors, arthralgias, pneumonitis, and gastrointestinal symptoms). While the toxic effects are due to 6-mercaptopurine, the hypersensitivity reactions are believed to be caused by the nitroimidazole moiety. A 21-year-old male patient developed end-stage renal failure due to antiglomerular basement membrane (AGBM) disease (rapidly progressive glomerulonephritis with linear immunoglobulin G deposits and positive circulating AGBM antibodies). The patient became dependent on continuous ambulatory peritoneal dialysis and, later, hemodialysis, and received two renal allografts at the ages of 23 and 27 years. He received three courses of azathioprine treatment: one course for AGBM glomerulonephritis and two courses for rejection episodes. Each course was followed within 4 to 7 days by symptoms compatible with Goodpasture's syndrome, ie, high fever, rigors, arthralgias, diarrhea, myalgias, and pulmonary infiltrates with hemoptysis. All signs and symptoms always resolved completely on discontinuation of azathioprine. During the treatment for rejections, AGBM antibodies were not elevated, and during one episode AGBM disease in the lung (Goodpasture's syndrome) was excluded by open lung biopsy. Treatment of a subsequent rejection episode with 6-mercaptopurine was well tolerated. We conclude that azathioprine hypersensitivity can mimic the pulmonary manifestations of Goodpasture's syndrome. Hypersensitivity probably is due to the nitroimidazole moiety of azathioprine. Thus, differential diagnosis of Goodpasture's syndrome (and probably of any "pulmonary renal syndrome") should include azathioprine hypersensitivity. PMID- 8203373 TI - Hyperbaric oxygen therapy in calciphylaxis-induced skin necrosis in a peritoneal dialysis patient. AB - A 58-year-old white woman on continuous ambulatory peritoneal dialysis for 2 years developed calciphylaxis-induced necrotic skin lesions over both lower extremities. Despite subtotal parathyroidectomy and other conventional measures, skin lesions continued to worsen. Mapping of transcutaneous oxygen pressure showed markedly low values in involved areas. Skin ulcers completely healed after 38 sessions of hyperbaric oxygen therapy. The results in our case indicate that hyperbaric oxygen therapy may be useful in the treatment of skin ulcers secondary to calciphylaxis. PMID- 8203374 TI - Mesangiolysis associated with bone marrow transplantation: new insights on possible etiogenic factors. PMID- 8203376 TI - Looking upon the water. Better "on" than "over" the hill. PMID- 8203375 TI - Chronic renal transplant rejection. AB - The most common cause of renal allograft failure, after the first year posttransplant, is chronic rejection (CR). The impact on allograft loss of CR has remained constant despite the improvements in immunosuppression that have occurred. This process is characterized by a gradual decline in graft function over months to years. Proliferation of vascular smooth muscle cells and fibrosis of the large arteries are the main pathologic characteristics of CR. The clinical course varies widely among patients, from stable function for years to graft failure within several months. The precipitating factors of CR may be many and are unknown. Chronic rejection is likely to be, at least in part, immune mediated. A history of acute rejection episodes correlates strongly with the development of CR. No method has been clearly shown to prevent or treat CR. PMID- 8203377 TI - Hospitals intend to pare employment, restructure. PMID- 8203379 TI - Initial triservice formulary ready for use. Pharmacoeconomic center will issue quarterly updates. PMID- 8203378 TI - Card-carrying HMO members test health record technology. PMID- 8203380 TI - FDA approves trimetrexate as second-line therapy for Pneumocystis carinii pneumonia. PMID- 8203382 TI - Downsizing. PMID- 8203381 TI - Money is not the only motivator. PMID- 8203384 TI - Management of orthostatic hypotension. AB - The pathogenesis, clinical manifestations, and management of orthostatic hypotension (OH) are reviewed. OH is a decline in blood pressure that occurs when one moves from a lying to a standing position that results in symptoms of cerebral hypoperfusion, most commonly lightheadedness and syncope. The disorder may result from primary autonomic disorders, such as Shy-Drager syndrome; reversible nonautonomic causes, such as reduced blood volume; underlying diseases, such as diabetes mellitus; and drugs. Elderly people are predisposed to OH. The diagnosis of OH is based on the documentation of postural hypotension accompanied by symptoms of cerebral ischemia. The goal of therapy is to relieve symptoms. Nonpharmacologic approaches are preferred and include increasing sodium intake, avoiding rapid postural changes, and wearing elastic garments. OH is difficult to treat pharmacologically because of varying responses and adverse effects. The drug of choice for all types of OH is fludrocortisone acetate, although caution must be used in patients with congestive heart failure. Prostaglandin synthetase inhibitors can also be used for all types of OH but have had more limited success. Sympathomimetics with or without monoamine oxidase inhibitors, beta-adrenergic antagonists, and ergot alkaloids should be administered only to patients with certain types of OH, and patients must be monitored closely. Clonidine, midodrine, yohimbine, octreotide, dopamine antagonists, desmopressin, and epoetin alfa have not been well studied and should be limited to patients with severe, refractory disease. Although no uniformly effective treatment regimen exists, OH can often be adequately managed with a combination of nondrug and drug therapies. PMID- 8203383 TI - Infection control in critically ill patients: effects of selective decontamination of the digestive tract. AB - The use of selective decontamination of the digestive tract (SDD) to control infection in the intensive care unit (ICU) is reviewed. There are three basic patterns of infection in the ICU: primary endogenous, secondary endogenous, and exogenous. In exogenous infection, no microbial carriage precedes colonization and infection. In endogenous infection, infection is preceded by oropharyngeal or GI carriage. A primary endogenous infection is caused by an organism carried by the patient on admission to the ICU, whereas a secondary endogenous infection is caused by organisms acquired in the ICU. The traditional approach to infection control in the ICU has included frequent hand washing, limiting the use of agents for prophylaxis of stress-ulcer bleeding, and limiting the use of injectable antimicrobials to the treatment of infection in order to prevent resistance. The recognition that hand washing only partially reduces endogenous infection led to the use of nonabsorbable antimicrobials to abolish oropharyngeal and gastrointestinal carriage of potentially pathogenic microorganisms. In addition, the use of an injectable antimicrobial during the first four days in the ICU to control primary endogenous infection was considered not to lead to resistance as long as it was combined with nonabsorbable antimicrobials. Of 41 fully reported clinical trials of SDD, 33 showed a significant reduction of infectious morbidity among patients who received SDD. Of the 32 trials in which carriage of potential pathogens was a measured endpoint, 31 showed a reduction in carriage. Of the 24 studies in which resistance was an endpoint, 22 showed no increase in resistance associated with SDD. Only 10 of 35 trials that examined death showed a significant decrease in mortality. SDD, used in conjunction with traditional infection-control measures, diminishes microbial carriage and infectious morbidity in the ICU without increasing antimicrobial resistance. PMID- 8203386 TI - Development and benefits of a pharmacy technician career ladder. AB - The development and benefits of a career ladder for pharmacy technicians are described. A career ladder for technicians was implemented at a 575-bed community hospital in 1989 to provide incentives for technicians to improve their skills and take on additional responsibilities. The ladder consisted of four steps, each requiring additional years of experience, proficiency at specific skills, and involvement in specific departmental activities (e.g., maintaining floor-stock medications, preparing i.v. admixtures, and implementing new policies and procedures). Pay increases were given with each move up the ladder. At the start of the program, eight technicians were placed at level 2 and the remaining 16 were placed at level 1. Three years after the ladder was implemented, annual technician turnover had decreased from 33% to 15%. Employee surveys suggested increased job satisfaction among the technicians. Reassignment of tasks to technicians (e.g., maintaining narcotic distribution and coordinating daily purchasing activities) increased scheduling flexibility and helped provide an additional eight hours per week for pharmacist involvement in patient care activities. A pharmacy technician career ladder was associated with lower technician turnover, expansion of technicians' job responsibilities, and an increase in pharmacists' time for clinical activity. PMID- 8203385 TI - Effect of drug interactions on outcomes of patients receiving warfarin or theophylline. AB - The effect of drug interactions on costs and other outcomes for hospitalized patients receiving warfarin or theophylline was studied. Data were collected from medical records during a one-year period in two community teaching hospitals in Maryland. The data included demographic information, the duration of study-drug therapy, the number of days spent in the intensive care unit, the length of stay (LOS) in the hospital, the number of prothrombin-time tests and serum theophylline assays, and the test results. A multiple-regression procedure was used to compare outcomes of patients who were prescribed specific drugs interacting with warfarin or theophylline with those of patients who were not. Among warfarin-treated patients, there was a significant difference in each outcome measure (LOS, number of laboratory tests, and test results) between those who received an interacting drug and those who did not; mean LOS was 3.14 days longer in patients given an interacting drug. No significant differences in outcome measures were observed between the two groups of theophylline-treated patients. The cost of the increased LOS attributed to the presence of a drug interacting with warfarin was estimated to range from $779 to $1005 per hospitalization. The cost of additional prothrombin-time tests was estimated at $19-$50. Patients who received warfarin and an interacting drug had an increased LOS, required more laboratory tests, and had longer prothrombin times than patients given warfarin alone; these differences probably led to higher costs. PMID- 8203387 TI - Program for procurement of drugs for indigent patients. AB - A program for procuring free medications for indigent patients from pharmaceutical manufacturers is described. A medical center that provides $36 million in free care annually to indigent patients sought a way to offset drug costs for these patients while maintaining the same level of care. The pharmaceuticals with the greatest impact on the pharmacy budget were identified; manufacturers of these pharmaceuticals were surveyed to determine if they offered free drugs to qualified patients. The net potential cost avoidance resulting from procuring these free drugs was estimated at $150,000 for the first year. A full time pharmacist was hired to identify patients likely to qualify for such assistance, help patients apply for assistance, and coordinate the receipt and distribution of the resulting medication supplies. The program served 200 patients the first year (fiscal year 1992) and more than 300 patients the next year. Medications obtained for these patients included i.v. immune globulin, cancer chemotherapy agents, growth factors, antimicrobials, antiemetics, and interferons. The acquisition cost of the medications received was $448,851 in 1992 and $504,211 in 1993. A pharmacy-based program to procure free medications for indigent patients has helped to defray a medical center's expense of providing care. PMID- 8203389 TI - Salary bonus program for staff pharmacists. PMID- 8203388 TI - Compatibility of piperacillin sodium plus tazobactam with selected drugs during simulated Y-site injection. AB - The compatibility of piperacillin sodium plus tazobactam with selected drugs during simulated Y-site administration was studied. A 5-mL sample of piperacillin sodium 40 mg/mL plus tazobactam 5 mg/mL (Zosyn) in 5% dextrose injection was combined with a 5-mL sample of each of 75 other drugs at concentrations used clinically. Each combination was prepared in duplicate in glass culture tubes, with the order of mixing being reversed between the duplicates; storage was in constant fluorescent light at 22 degrees C. The admixtures were examined visually in normal fluorescent light and in high-intensity light zero, one, and four hours after preparation. A turbidimeter was used to measure the turbidity of each drug combination at the same intervals. Samples showing visual or turbidimetric evidence of incompatibility were subjected to particle sizing and counting. The majority of the drugs tested were compatible with Zosyn injection; most combinations had a turbidity of less than 0.1 nephelometric turbidity unit. However, 24 drugs exhibited various incompatibilities, including increased turbidity, particulate formation and precipitation, and color change. Piperacillin sodium 40 mg/mL plus tazobactam in 5% dextrose injection was visually compatible with the majority of the drugs tested for up to four hours at 22 degrees C but incompatible with 24 drugs. PMID- 8203390 TI - Development of a statewide medication-review program. PMID- 8203391 TI - Admissibility of scientific testimony into evidence. PMID- 8203392 TI - Challenges in providing pharmaceutical care to pediatric patients. PMID- 8203393 TI - Clinical pharmacy practice in urban China. PMID- 8203394 TI - Pitfalls of using antimicrobial order forms to evaluate drug use. PMID- 8203396 TI - Computerized detection of potential drug-enteral nutrition product problems. PMID- 8203395 TI - Clinical interventions reduce antimicrobial costs. PMID- 8203397 TI - Circumcision: quality isn't the only dilemma. PMID- 8203398 TI - Circumcision: quality isn't the only dilemma. PMID- 8203399 TI - Codependency knows no bounds. PMID- 8203401 TI - No 'sterile cockpits,' please. PMID- 8203400 TI - Codependency knows no bounds. PMID- 8203403 TI - HIV wasting. How to stop the cycle. PMID- 8203402 TI - Beware of trailing zeros. PMID- 8203404 TI - Four strategies for keeping patients satisfied. PMID- 8203405 TI - The gift of life: talking to families about organ and tissue donation. PMID- 8203406 TI - Test your wound assessment skills. PMID- 8203407 TI - Understanding modes of mechanical ventilation. AB - Caring for patients receiving mechanical ventilation may be new to you, but it's almost certain that you'll be seeing them more often in the future. The modes of ventilation and assessment parameters discussed here will help you meet the special needs of these challenging patients. PMID- 8203408 TI - To Russia, with love. PMID- 8203409 TI - Responding quickly to hypoglycemia. PMID- 8203410 TI - Six ways to take this job...and love it! PMID- 8203411 TI - Reminiscence, her way. PMID- 8203412 TI - Changing standard in consumer-provider relations. PMID- 8203413 TI - My patient died today. PMID- 8203414 TI - Return to excellence. PMID- 8203415 TI - Abruptio placentae: perinatal outcome in normotensive and hypertensive patients. AB - OBJECTIVE: The objective of this study was to compare perinatal outcomes of hypertensive and normotensive women experiencing abruptio placentae. Our hypothesis is that hypertensive women have a less favorable perinatal outcome than do normotensive women. STUDY DESIGN: Women with the diagnosis of abruptio placentae delivered between July 1, 1988, and May 31, 1992, composed the study group (n = 226) in this case-control study. The incidence of abruptio placentae was 0.7% during this time. Those women with either multifetal gestations (n = 4) or delivery before 20 weeks' gestation (n = 2) were excluded from data analysis. The remaining 220 patients were divided according to their hypertensive (n = 29) or normotensive (n = 191) status. Maternal and neonatal medical records were reviewed and abstracted for demographic variables, antepartum complications, delivery route, abruptio placentae grade, neonatal gender, birth weight, Apgar score, cord pH, and perinatal mortality. These perinatal outcome variables were compared between the hypertensive and normotensive patient groups. RESULTS: Black women with abruptio placentae were significantly more likely to be hypertensive (p = 0.0078). Hypertensive women with abruptio placentae had the antepartum complication diabetes mellitus significantly more often than did normotensive women (p = 0.032). However, they were similar to normotensive women with regard to the frequency of positive urine drug screen and trauma. Hypertensive women were no more likely to be delivered before 32 or 37 weeks' gestation, have neonates weighing < 1500 or 2500 gm, or to be delivered by cesarean section. Abruptio placentae grades 2 and 3 occurred more often in hypertensive women (p = 0.053), as did significantly lower umbilical cord artery (p = 0.005) and venous (p = 0.003) pH values. Neonates from hypertensive women were no more likely to have low 5-minute Apgar scores or to die than those from normotensive women. CONCLUSION: Although hypertensive women experiencing abruptio placentae are more likely to have higher-grade abruptio placentae and lower umbilical cord pH values, the overall perinatal outcome was not significantly different from that of normotensive women experiencing abruptio placentae. PMID- 8203416 TI - A comparison of single versus multiple growth ultrasonographic examinations in predicting birth weight. AB - OBJECTIVE: Our purpose was to determine whether two or more ultrasonographic fetal growth assessments provide a superior estimate of birth weight than does a single examination. STUDY DESIGN: Five hundred and eighty five ultrasonographic procedures were performed in 263 patients, divided into single (n = 249) and multiple (n = 247) examination groups. Ultrasonographically estimated fetal weight percentiles and abdominal circumference percentiles were compared with gestationally corrected birth weight percentiles. After the gestational age range with the fewest errors in birth weight percentile prediction (32 to 36 weeks) was determined, patients with a single examination in this range were assigned to the single examination group. In the group with multiple examinations averaged ultrasonographic percentiles were used to predict birth weight percentile. Mean absolute and percentage errors were compared for predictive accuracy by means of analysis of variance and Student t test. RESULTS: There was a linear correlation between the estimated fetal weight and abdominal circumference percentiles and the birth weight percentile, (r = 0.72, p < 0.0001). The accuracy of birth weight percentile predictions was similar whether one or multiple examinations were performed in the third trimester. Both the abdominal circumference percentile and estimated fetal weight percentile underpredicted birth weight, although the abdominal circumference percentile errors (1% to 2%) were statistically smaller than those derived from estimated fetal weights percentile (9% to 11%, p < 0.0001). Both abdominal circumference percentile and estimated fetal weights percentile consistently overidentified fetuses < 10th percentile (small for gestational age) and underidentified fetuses > 90th percentile (large for gestational age). However, multiple abdominal circumference percentile measurements resulted in improved predictions for small for gestational age (sensitivity 100%, specificity 88%) and large for gestational age (sensitivity 84%, specificity 100%). CONCLUSIONS: With either the single or multiple examination approach birth weight percentile estimates were within 10% of the actual birth weight percentile approximately 50% of the time. Multiple ultrasonographic examinations provided little improvement in prediction of birth weight compared with a single observation. Multiple measurements of the abdominal circumference percentile may provide improved accuracy in identifying large for gestational age and small for gestational age fetuses. PMID- 8203417 TI - A reanalysis of the Cu-7 intrauterine contraceptive device clinical trial and the incidence of pelvic inflammatory disease: a paradigm for assessing intrauterine contraceptive device safety. AB - OBJECTIVE: We calculated and compared the incidence of pelvic inflammatory disease in a 10% random sample of the Cu-7 intrauterine contraceptive device (G.D. Searle & Co., Skokie, Ill.) clinical trial with the rates reported to the Food and Drug Administration and those in subsequent trials published in the world literature. STUDY DESIGN: A 10% random sample of the Cu-7 clinical trial was examined because calculations had demonstrated this random sample to be sufficient in size (n = 1614) to detect a difference in rates of pelvic inflammatory disease from those reported to the Food and Drug Administration. An audit of a subset of the patient files, compared with the original files in Skokie, Illinois, confirmed that the files available for analysis were complete. Standard definitions were used to identify cases of pelvic inflammatory disease and to calculate rates of pelvic inflammatory disease. The world literature on Cu 7 clinical trials was reviewed. RESULTS: The calculated crude and Pearl index rates of pelvic inflammatory disease were consistent with those rates previously reported to the Food and Drug Administration and published in the medical literature. Life-table pelvic inflammatory disease rates were not different between nulliparous and parous women and pelvic inflammatory disease did not differ from basal annual rates in fecund women. CONCLUSION: On the basis of the analysis of this 10% sample, the pelvic inflammatory disease patient rates reported to the Food and Drug Administration for the entire Cu-7 clinical trial are accurate and are similar to those published in the world literature. PMID- 8203418 TI - The effects of RU 486 and leuprolide acetate on uterine artery blood flow in the fibroid uterus: a prospective, randomized study. AB - OBJECTIVE: Our purpose was to examine the effects of RU 486 and leuprolide acetate on uterine artery blood flow and uterine volume. STUDY DESIGN: Patients were randomly assigned to group A (eight patients) receiving 25 mg of RU 486 daily for 3 months or group B (six patients) receiving 3.75 mg of leuprolide acetate monthly for 3 months. Uterine artery blood flow change was determined by resistive index by means of vaginal color Doppler ultrasonography. Uterine volume was measured before and during the study with abdominal ultrasonography. RESULTS: Both groups showed an increase in resistive index. Patients receiving RU 486 had uterine artery blood flow decreased by 40%, and those receiving leuprolide acetate had a 21% decrease. We noted a significant decrease in uterine volume compared with pretreatment in both groups at 3 months. There was no significant decrease between groups. CONCLUSION: Both RU 486 (25 mg daily) and leuprolide acetate (3.75 mg monthly) are effective in decreasing blood flow to the uterus (increasing resistive index) and decreasing uterine volume at 3 months. A significant decrease in uterine artery blood flow may provide a mechanism for the decrease in uterine size and the decrease in uterine blood loss at the time of surgery. PMID- 8203419 TI - The choice of a gonadotropin-releasing hormone analog influences outcome of in vitro fertilization treatment. AB - OBJECTIVE: Our purpose was to determine if there is a difference in outcome associated with choice of gonadotropin-releasing hormone analog in in vitro fertilization treatment cycles. STUDY DESIGN: A retrospective analysis of 510 consecutive in vitro fertilization cycles with patient-selected use of either nafarelin (Synarel) or leuprolide (Lupron) was performed. RESULTS: Of 510 consecutive patient cycles, 284 patients (56%) chose nafarelin and 226 (44%) chose leuprolide. In the nafarelin group 64 cycles (34% of retrievals) resulted in deliveries. In the leuprolide group 37 (24%) resulted in delivery (p < 0.05). There were 260 patients in their first cycle of treatment, with 157 (60%) choosing nafarelin, resulting in 33 deliveries (34% per retrieval). Leuprolide, used in 103 (40%) of first cycles, resulted in 12 deliveries (20% per retrieval), (p = 0.052). CONCLUSIONS: In a large population of unselected patients undergoing in vitro fertilization the choice of nafarelin was associated with a significantly better outcome in terms of successful pregnancies achieved. PMID- 8203420 TI - A hospital review of advanced gynecologic endoscopic procedures. AB - OBJECTIVE: Our purpose was to review the findings of a Gynecologic Endoscopic Review Committee established to monitor and review operative endoscopic procedures performed by the staff at a large private hospital, Swedish Hospital Medical Center, in Seattle. STUDY DESIGN: Hospital charts of patients undergoing the endoscopic procedures under review are pulled monthly, and the data are extracted, particularly as related to performance of the procedures, length of surgery and hospitalization, and occurrence of complications. This study is a compilation of the committee's review of a 15-month interval, Jan. 1, 1992, to March 31, 1993. RESULTS: Forty-two surgeons performed 227 endoscopic procedures on 218 patients, 100 hysteroscopically and 127 laparoscopically. Significant complication rates were associated with the transhysteroscopic operative procedures and with many of the translaparoscopic procedures, including oophorectomy, ovarian cystectomy, myomectomy, pelviscopic lysis of adhesions, and laparoscopic-assisted vaginal hysterectomy. CONCLUSIONS: A significant complication rate was found for many of the advanced endoscopic procedures performed at Swedish Hospital Medical Center. This is likely related to operator inexperience in performing relatively difficult endoscopic procedures involving new and ever-expanding arrays of techniques and instruments. PMID- 8203421 TI - Intrathecal narcotics for obstetric analgesia in a community hospital. AB - OBJECTIVE: Our objective was to establish whether intrathecal narcotics for obstetric analgesia offer an adequate and cost-effective alternative to epidural analgesia with minimal side effects in our small, semirural community hospital with limited anesthesia coverage. STUDY DESIGN: Low-risk patients at > or = 35 gestational weeks in active labor were offered intrathecal narcotics. A retroactive chart review of every patient receiving an intrathecal injection was compared with a chart review of the next consecutive low-risk patient who did not receive an intrathecal narcotic. Age, parity, and status of labor at the time of application were noted, as was the subsequent rate of labor and the type of delivery. Side effects such as changes in vital signs, headache, vomiting, pruritus, urinary retention, and/or respiratory depression were noted. All study patients received fentanyl, 25 to 35 micrograms, plus 0.25 to 0.3 mg of preservative-free morphine combined with 6 to 8 mg of lidocaine. Within 15 minutes of delivery intravenous nalbuphine (Nubain), 5 mg, and oral naltrexone, 12.5 mg, were administered. Pain relief was recorded as excellent, satisfactory, or unsatisfactory (requiring additional medication). RESULTS: During the 30-month review period, 90 patients (3% of total deliveries) received intrathecal narcotics. There were three sets of twins, for a total of 93 live births. Ten patients (11%) required primary cesarean section, and of the 83 vaginal births 35 (38%) were spontaneous, two (2%) required forceps deliveries, and 46 (49%) were delivered by vacuum extraction, which was significantly higher than the 28 (31%) for controls. The rate of labor was not affected, with both groups requiring a similar rate of oxytocin (Pitocin) augmentation. Significantly more patients receiving intrathecal narcotics experienced pruritus and urinary retention compared with controls. There was no incidence of respiratory depression. Eighty four (93%) of the 90 patients reported excellent pain relief, five patients had satisfactory relief lasting 2.5 to 6 hours, and one was unsatisfactory. CONCLUSIONS: In our hospital with limited anesthesia services intrathecal narcotics offer excellent labor pain relief with manageable side effects and without adverse obstetric outcome. PMID- 8203422 TI - The second-born twin: can we improve outcomes? AB - OBJECTIVE: Second-born twin outcome was compared with that of the first-twin birth mate to determine whether there were differences, the reason for the differences, if any, and the clinical decisions that could be made to eliminate or ameliorate these differences. STUDY DESIGN: Twin pregnancies from 1989 through 1992 were retrospectively reviewed. Charts demonstrating both twins stillborn, either twin weighing < 500 gm, or either twin with a serious congenital anomaly were excluded from evaluation. After these exclusions 200 twin pairs remained for analysis. Each twin was compared directly with its birth mate. The first twin is postulated as having the best possible outcome for the pregnancy involved, and second-twin outcomes are compared with these. RESULTS: The second-born twin was more likely to be intubated, have respiratory distress syndrome, need resuscitation, and have lower 5-minute Apgar scores. Second-born twins had more nursery complications. The < 1500 gm group appeared to be at special risk. In this group there were more second-born twin neonatal deaths and much higher rates of intubation and resuscitation. Nonvertex presentation in the second-born twin increased chances for resuscitation, intubation, respiratory distress syndrome, and nursery complications. These outcomes in the second-born were not affected by cesarean delivery. CONCLUSIONS: The second-born twin is at increased risk of untoward outcome compared with its birth mate. Some of this risk can be attributed to birth weight. The risk posed by nonvertex presentation is small. Cesarean section delivery does not appear to eliminate the difference between first- and second-twin outcome. Prospective studies are needed. PMID- 8203423 TI - Curriculum change in an obstetrics-gynecology residency program and its impact on pregnancy in residency. AB - OBJECTIVE: Our purpose was to determine whether pregnancy was better tolerated by the individual female resident and the program as a whole after changes in the curriculum. STUDY DESIGN: The 1983 through 1992 graduates of an obstetrics gynecology residency program were questioned to assess the stress experienced by all residents and by the pregnant female residents. The level of agreement to statements expressing support and resentment for pregnancy in residency was measured. RESULTS: Resentment among residents toward their pregnant colleagues was significantly greater in 1983 through 1987 than in 1988 through 1992. Male residents expressed more resentment toward pregnancy in their colleagues than did female residents, but they were perceived by the pregnant female residents as equally supportive as female residents. The level of stress experienced by the 1983 through 1987 graduates was greater than by those from 1988 through 1992. CONCLUSION: Reducing the workload in training programs is associated with a decrease in the resentment of the residents toward pregnant residents and in the overall stress of the program. PMID- 8203424 TI - Perinatal outcome with the modified biophysical profile. AB - OBJECTIVE: Our purpose was to evaluate perinatal outcomes in high-risk pregnancies monitored with a modified biophysical profile. STUDY DESIGN: All non insulin-dependent patients referred for antepartum fetal surveillance received a modified biophysical profile biweekly. A modified biophysical profile is a combination of a nonstress test and an amniotic fluid index. Patients with a singleton gestation and intact membranes were entered into a protocol of randomized backup testing for an abnormal modified biophysical profile. Those patients having a nonreactive fetal heart rate, significant variable decelerations, late decelerations, or an amniotic fluid index < or = 5.0 cm received either a contraction stress test or a biophysical profile immediately. Once randomized, a patient received the same backup test, when indicated, with subsequent testing. RESULTS: A total of 2774 patients had 17,429 tests with an uncorrected perinatal mortality rate of 2.9 per 1000. The overall incidence of an adverse perinatal outcome (i.e., perinatal death or nursery death before infant hospital discharge, cesarean delivery for fetal distress within the first 2 hours of labor, 5-minute Apgar score < 7, neonatal seizures or grade III or IV central nervous system hemorrhage) was 7.0%. When compared with patients having persistently normal modified biophysical profile, patients requiring a backup test had a significantly greater incidence of adverse perinatal outcome (9.3% vs 4.9%, p < 0.001, odds ratio 2.0, 95% confidence interval 1.5 to 2.7) and small for-gestational-age infants (5.2% vs 2.4%, p < 0.001, odds ratio 2.2, 95% confidence interval 1.5 to 3.5). No differences in outcomes between patients randomized to a contraction stress test versus a biophysical profile could be identified either overall or in limiting the analysis to outcome after a negative last test. However, patients having contraction stress test as a backup test had a significantly higher rate of intervention for an abnormal test result than did those having a biophysical profile backup test (23.7% vs 16.6%, p < 0.002, odds ratio 1.6, 95% confidence interval 1.2 to 2.1). CONCLUSION: The modified biophysical profile is an excellent means of fetal surveillance and identifies a group of patients at increased risk for adverse perinatal outcome and small-for gestational-age infants. There does not appear to be a significant benefit with the contraction stress test compared with the biophysical profile as a backup test. Further, the contraction stress test is associated with a higher rate of intervention for an abnormal test than is the biophysical profile. PMID- 8203427 TI - Three consecutive pregnancies in a patient with glycogen storage disease type IA (von Gierke's disease). AB - Glycogen storage disease type IA is associated with metabolic abnormalities that can compromise fetal outcome. Normal outcome can be achieved by maintaining euglycemia throughout gestation. We report three consecutive pregnancies in a patient with glycogen storage disease type IA. The patient, a 35-year-old woman, has been maintained on a regimen of nightly nasogastric or cornstarch feedings for the past 12 years with improving metabolic control, reduced liver size, and no progression of multiple hepatic adenomas. On confirmation of each pregnancy, early in the first trimester nightly feeding was changed from cornstarch ingestion to Polycose by nasogastric intubation, with good metabolic control. During the last trimester of each pregnancy metabolic control showed further improvement, with lowering of lactate, urate, and triglyceride levels. During the first pregnancy unexpected fetal death occurred at 33 weeks. During the last two pregnancies, the patient was admitted at 33 and 34 weeks, respectively, for closer supervision of metabolic status and fetal monitoring. She underwent a cesarean section at 35 weeks 4 days of gestation and was delivered of a girl. She underwent a repeat cesarean section at 35 weeks 2 days for the subsequent gestation and was delivered of a boy. Both infants are healthy and appear to be unaffected by von Gierke's disease. Hepatic adenomas did not enlarge during the pregnancies. Meticulous management resulted in normal pregnancy outcomes in two consecutive gestations. Rapid fetal growth late in the third trimester may require particularly careful supervision to maintain euglycemia. PMID- 8203426 TI - Placenta previa: antepartum conservative management, inpatient versus outpatient. AB - OBJECTIVE: Our purpose was to compare outcomes of patients with placenta previa managed expectantly in either an inpatient or outpatient setting. STUDY DESIGN: Records for 238 patients coded as having placenta previa over the 12-year period from 1981 through 1992 were reviewed, and outcomes were compared. RESULTS: A total of 104 patients were managed conservatively (i.e., delivered > 7 days after diagnosis). Fifty-five patients were hospitalized and 49 were followed up as outpatients. There was no significant difference in gestational age or birth weights at delivery. Likewise, the average lowest postpartum hemoglobins were similar. Infant morbidity was similar when incidences of respiratory distress syndrome, transient tachypnea of the newborn, and intraventricular hemorrhage were compared. CONCLUSION: Although there may have been other circumstances segregating patients to hospital care or home care, there was no apparent difference in the outcome of the two groups. PMID- 8203425 TI - Cisplatin, doxorubicin hydrochloride, and cyclophosphamide followed by radiotherapy in high-risk endometrial carcinoma. AB - OBJECTIVE: Our purpose was to assess the effect of adjuvant platinum-based, multiagent chemotherapy followed by conventional radiotherapy on the recurrence free interval, patterns of recurrence, and survival of women with completely resected, poor-prognosis endometrial carcinoma. STUDY DESIGN: Surgical stage IC and II endometrial carcinomas involving the outer one third of myometrium and completely resected stage III and IV carcinomas were eligible for six cycles of cisplatin (Platinol), doxorubicin hydrochloride (Adriamycin), and cyclophosphamide (Cytoxan) (50, 50, 500 mg/m2), followed by external beam radiotherapy to pelvis, pelvis and periaortic chain, or whole abdomen, on the basis of documented disease. RESULTS: Forty-seven women were registered between April 1, 1984, and Oct. 10, 1992; 39 were eligible for review. Six were stage I, 28 were stage III, and five were stage IV. Two tumors were grade I, eight were grade 2, and 29 were grade 3. Twenty-three were endometrioid adenocarcinomas, eight papillary serous, six adenosquamous, and two clear cell. Thirty-seven patients (94.9%) completed six courses of chemotherapy, with no deaths ascribed to treatment. Grade 3 or 4 neutropenia was experienced by 17 (44%) and sepsis by three (8%). Current median follow-up is 27.3 months. Fifteen patients (38.5%) have recurrence, and 14 have died after a median interval of 26.9 months. The 2 year progression-free interval is 72.5% for nonpapillary serous histologic types and 22.5% for papillary serous cancers (p = 0.0074). CONCLUSION: Adjuvant chemotherapy with Platinol, Adriamycin, and Cytoxan followed by radiation therapy is well tolerated and seems to confer a survival advantage to women with nonpapillary serous endometrial carcinoma with a poor prognosis compared with historic controls treated by surgery or radiotherapy. PMID- 8203428 TI - Donor insemination and human immunodeficiency virus: a risk/benefit analysis. AB - In 1988 the American Fertility Society revised its guidelines for the use of semen in donor insemination by stating that "the use of fresh semen for donor insemination is no longer warranted." Although the consequences of this recommendation include an approximate doubling of the patient's cost of treatment, a 50% reduction in both cycle fecundity and 3-month life-table pregnancy rates, a reduction in the number of pregnancies because of patient dropout, and an ethically troubling increase in physician income as a direct result of the diminished efficacy of treatment, an analysis of the risk of transmission of human immunodeficiency virus through donor insemination has not been presented. All available data suggest that neither safety nor efficacy need be sacrificed in the current practice of donor insemination by offering patients the choice of appropriately screened fresh or frozen sperm. PMID- 8203429 TI - Screening transvaginal ultrasonography of postmenopausal women in a private office setting. AB - OBJECTIVE: The objective of this study was to determine the value of screening transvaginal ultrasonography for the evaluation of endometrial or ovarian abnormalities in asymptomatic postmenopausal women in a private gynecology office at the time of yearly examination. STUDY DESIGN: All postmenopausal women who were seen for yearly examination between June 1, 1991, and June 1, 1993, underwent screening transvaginal ultrasonographic examinations that I performed. Women who had any pelvic symptoms or who were premenopausal were excluded from the study group. RESULTS: During the 24 months of this study 478 women were screened. One case of early ovarian carcinoma was diagnosed, one case of superficial adenocarcinoma of the endometrium was discovered, and 28 other ovarian cysts were seen. All women with cystic changes in the ovaries underwent testing for serum CA 125 levels, and follow-up ultrasonography was done at 1 and 3 months. Ovaries were removed if the CA 125 level was elevated, if the cyst became larger, or if the patient desired. No additional ovarian carcinomas were found in those women who had cysts discovered on ultrasonography and who subsequently had the ovaries removed. CONCLUSIONS: Screening transvaginal ultrasonography examinations were well received by all patients, there was no significant associated discomfort, the scans required minimal time, and a significant number of abnormalities were discovered, including two early carcinomas. I believe that when transvaginal ultrasonography is available in an office setting, where it can be performed at no or very low cost, routine screening of postmenopausal women is a valuable addition to the yearly examination. PMID- 8203430 TI - Determination of fetal acidemia at birth from a remote umbilical arterial blood gas analysis. AB - OBJECTIVE: Sampling of the umbilical artery for determination of acid-base status is performed within 60 minutes of birth, but is not feasible in all hospitals on a 24-hour basis. A desirable alternative would be to perform the arterial cord blood gas analysis hours after the sample was obtained at delivery with reliable identification of whether the newborn was acidotic. STUDY DESIGN: After 19 deliveries multiple umbilical arterial blood samples were withdrawn into five preheparinized syringes, and these were analyzed at 0.5, 15, 30, 45, and 60 hours after delivery. On the basis of observed changes in pH and base deficit over 60 hours, two separate regression equations were generated. These two equations permit calculation of the original pH and base deficit if the following are known: (1) the time interval from delivery to blood gas analysis and (2) the values of the remote pH and remote base deficit. The regression models were validated among 23 subsequent deliveries to assess how accurately they identified newborn acid-base status at birth. RESULTS: The original pH and base deficit can be calculated with two separate equations from linear regression models if two variables are known: the results of the remote umbilical arterial blood gas analysis and time intervals from delivery to analysis. Of 23 newborns during the validation phase of the study, 16 were not acidotic, one had respiratory acidosis, and six had metabolic acidosis. The second umbilical arterial blood gas analysis was performed at a mean (+/- SD) interval of 53.8 +/- 41.5 hours (range 7.5 to 138 hours). The remote gas analysis inaccurately identified 68.7% (11/16) of nonacidotic newborns as being acidotic at birth. However, insertion of these data into these equations produced results with none of the newborns predicted to have normal acid-base when they were acidotic at birth or predicted to be acidotic when the cord pH was normal. CONCLUSIONS: Use of these mathematic models allows the clinician to perform an umbilical arterial blood pH analysis < or = 60 hours after delivery yet with accurate estimation of true acid-base status at birth. PMID- 8203432 TI - How to be a good doctor in the 1990s: stand and deliver. PMID- 8203431 TI - Structural support of the urethra as it relates to stress urinary incontinence: the hammock hypothesis. AB - OBJECTIVE: This study examines the anatomic factors that could explain the mechanical basis for transmission of abdominal pressure to the urethra. STUDY DESIGN: Dissection of 19 embalmed and 42 fresh cadavers and examination of 13 sets of serial pelvic sections were performed to study the structures involved in urethral support. The effect of simulated increases in abdominal pressure on the pelvic floor and urethra was observed in fresh specimens. RESULTS: The urethra lies on a supportive layer that is composed of the endopelvic fascia and the anterior vaginal wall. This layer gains structural stability through its lateral attachment to the arcus tendineus fascia pelvis and levator ani muscle. Pressure from above compresses the urethra against this hammock-like supportive layer, compressing its lumen closed. The stability of the suburethral layer depends on the intact connection of the vaginal wall and endopelvic fascia to the arcus tendineus fasciae pelvis and levator ani muscles. CONCLUSION: Increases in urethral closure pressure during a cough probably arise because the urethra is compressed against a hammock-like supportive layer, rather than the urethra being truly "intraabdominal." PMID- 8203433 TI - Antepartum diagnosis of noncoiled umbilical cords. AB - OBJECTIVE: The null hypothesis is that fetuses with noncoiled umbilical cords diagnosed in the antepartum period will have outcomes no different from those with normally coiled cords. STUDY DESIGN: We prospectively gathered data from Jan. 1 through May 18, 1992, from all fetuses undergoing routine ultrasonographic evaluation. The outcomes of fetuses noted to have noncoiled umbilical cords were compared with those of a control group of fetuses with normally coiled cords. The control group consisted of those subjects undergoing ultrasonography during the study period who were ultimately transferred to our perinatal practice for the remainder of the pregnancy (i.e., the highest-risk patients). Two outcome parameters were selected for comparison: fetal anomalies and fetal death. RESULTS: Six hundred eighty-seven consecutive ultrasonographic examinations were performed. Twenty-five subjects (3.7%) had noncoiled umbilical cords identified ultrasonographically (mean gestational age at diagnosis 20.3 +/- 3.5 [SD] weeks). The control group had 197 subjects. The combined incidence of fetal anomalies or death in the noncoiled group (16%) was significantly greater (p < or = 0.05, relative risk 4.6 [95% confidence interval 1.41 to 14.15]) than that of the control group (3.5%). The noncoiled group had two fetal deaths (8%), whereas two deaths (1%) occurred among controls (p < or = 0.05, relative risk 8 [95% confidence interval 1.16 to 50]). Two (8%) fetal anomalies (anencephaly, prune belly syndrome) occurred in the noncoiled group, whereas the controls (n = 197) had five fetuses (2.5%) with anomalies (not significant). CONCLUSION: The antepartum identification of noncoiled umbilical cords appears to be a risk factor for suboptimal pregnancy outcome. PMID- 8203434 TI - Is it time to reassess the risk for the growth-retarded fetus with normal Doppler velocimetry of the umbilical artery? AB - OBJECTIVE: Previous studies demonstrate an association between abnormal umbilical artery Doppler velocimetry and the birth of a small-for-gestational-age infant and between abnormal result and adverse neonatal outcome. The hypothesis is that preterm growth-retarded infants with normal antenatal velocimetry have outcomes similar to other preterm infants, whereas preterm small-for-gestational-age infants with abnormal Doppler results define a subgroup with increased morbidity. STUDY DESIGN: For 100 live-born infants, at risk for fetal growth retardation and undergoing antenatal Doppler and targeted ultrasonographic examinations, we assessed a number of complete neonatal outcome parameters. RESULTS: Ten neonatal deaths occurred in the study population, seven with abnormal Doppler results and three with normal Doppler results. Of the 90 surviving infants, gestational age at delivery was not different between the Doppler normal and abnormal neonates, whereas birth weight (1714 gm vs 1379 gm) was higher in the Doppler normal group (p = 0.006). The presence of intraventricular hemorrhage (20% vs 6%) was higher in the abnormal group (p = 0.05). Abnormal Doppler results defined an infant group destined for prolonged hospitalization, mean intensive care days (21 vs 9), and special care nursery days (25 vs 9). Thirty-eight percent of small-for gestational-age babies had a normal Doppler result. Analysis of variance indicated small-for-gestational-age infants with abnormal Doppler results (n = 20) had a mean intensive care unit stay of 31 days, significantly different (p = 0.005) from small-for-gestational-age infants with normal Doppler results (n = 14), non-small-for-gestational-age infants with abnormal results (n = 21), and non-small-for-gestational-age infants with normal results (n = 35) whose mean intensive care unit stays were 14, 12, and 7 days, respectively. Gestational age at delivery (33.0 weeks) was not different among these groupings, not accounting for the observed differences. CONCLUSION: Normal antenatal velocimetry defines a distinct subgroup of preterm small-for-gestational-age infants at less risk for prolonged hospitalization compared with those with abnormal velocimetry. PMID- 8203435 TI - Gonadotropin-releasing hormone agonist use before hysterectomy. AB - OBJECTIVE: Our purpose was to compare the effects of leuprolide acetate in patients with symptomatic uterine leiomyoma before hysterectomy. STUDY DESIGN: Group I (n = 90) included patients with a pretreatment uterine size of 14 to 18 gestational weeks and group II (n = 60) included patients with uteri > 18 weeks' gestational size. Patients in both groups were randomized to either immediate hysterectomy or 2 months of preoperative gonadotropin-releasing hormone agonist. RESULTS: All patients in the two groups with a pretreatment hemoglobin < 11.0 gm/dl randomized to agonist had a significant (p < 0.05) increase (> or = 1.5 gm/dl) in hemoglobin level. Patients in group I who received preoperative agonist were more likely to undergo vaginal hysterectomy (80% vs 13%, p < 0.05) than were patients who did not receive preoperative agonist. Patients undergoing vaginal hysterectomy had a shorter hospital stay, decreased operative blood loss, and a shorter convalescence period than did those undergoing abdominal hysterectomy. In group II, in spite of a mean uterine volume reduction of 51.3%, intraoperative morbidity, operative blood loss, hospital stay, and postoperative convalescence period did not differ between treatment arms. CONCLUSION: The preoperative administration of gonadotropin-releasing hormone agonist in patients with a uterus of 14 to 18 weeks' size increases the use of vaginal hysterectomy, decreases intraoperative blood loss, and shortens hospital stay and convalescence. Preoperative gonadotropin-releasing hormone agonist for patients with a preoperative hemoglobin < 11.0 gm/dl reduces the risk of preoperative transfusion. Preoperative gonadotropin-releasing hormone use in the nonanemic patient with a uterine size > or = 18 weeks' gestational size doses not appear to lower operative morbidity. PMID- 8203436 TI - Tumor necrosis factor-alpha is elevated in plasma and amniotic fluid of patients with severe preeclampsia. AB - OBJECTIVE: Our purpose was to investigate whether markers for activation of the immune system are present in patients with preeclampsia by assessing maternal plasma and amniotic fluid for tumor necrosis factor-alpha and interleukin-1 beta. STUDY DESIGN: Twenty-one patients with severe preeclampsia composed the study group (group A). An antepartum comparison group was composed of healthy nulliparous patients not in labor and matched for gestational age (group B). Another control group consisted of term nulliparous patients in labor with uneventful pregnancies (group C). Maternal plasma samples were collected from all patients at recruitment and from patients in groups A and C immediately after delivery and again 20 to 24 hours post partum. Amniotic fluid was also collected from patients in groups A and C during labor. All samples were collectively assayed for tumor necrosis factor-alpha and interleukin-1 beta by specific enzyme linked immunoassays. RESULTS: Before labor tumor necrosis factor-alpha was detected more frequently in the plasma of preeclamptic patients than in the plasma of patients in group B (12/16 vs 5/16, p < 0.05) and in higher concentrations (median 35 pg/ml vs median 0 pg/ml, p < 0.05). Although tumor necrosis factor-alpha was frequently detected in the plasma of patients in group C in early labor (16/20), concentrations were higher in the four preeclamptic patients first sampled in early labor (210 pg/ml vs 65 pg/ml, p < 0.05). Similarly, amniotic fluid levels of tumor necrosis factor-alpha were increased in preeclamptic patients compared with control patients. At delivery tumor necrosis factor-alpha was more likely to be identified in the plasma of preeclamptic patients and was found in higher concentrations, but by 20 to 24 hours post partum measurements in the preeclamptic and control patients were similar. There were no differences in the frequency with which interleukin-1 beta was detected or the concentration of interleukin-1 beta in any of the samples. CONCLUSIONS: Tumor necrosis factor-alpha is increased in the plasma and amniotic fluid of patients with severe preeclampsia. These data are suggestive of a role for abnormal immune activation in the pathophysiologic mechanisms of preeclampsia. PMID- 8203437 TI - Perinatal morbidity associated with violence experienced by pregnant women. AB - OBJECTIVE: We investigated whether physical assault is independently associated with an adverse obstetric outcome. STUDY DESIGN: We compared the perinatal outcomes of 32 indigent women who reported being physically abused during pregnancy with those of 352 control subjects who denied ever being assaulted. Patients were classified into the appropriate category on the basis of a structured interview. Logistic regression analyses were performed to estimate the relative risk of adverse outcome while adjusting for confounders. RESULTS: Women assaulted in the current pregnancy were twice as likely to have preterm labor as compared with those who denied assault. In addition, crude odds ratios showed a twofold increased risk of chorioamnionitis in assault victims. No difference between abused and nonabused women was noted in the prevalence of preterm delivery, pregnancy-induced hypertension, cesarean section, meconium staining, infant birth weight, Apgar scores, intrauterine growth retardation, fetal distress, fetal death, neonatal seizures, sepsis, or admission to the intensive care unit. CONCLUSIONS: This study demonstrates that physical assault during pregnancy is associated with preterm labor and chorioamnionitis. Screening for ongoing assault should be incorporated into routine prenatal care to identify women at risk of complications. PMID- 8203438 TI - In utero surgical treatment of fetal obstructive uropathy: a new comprehensive approach to identify appropriate candidates for vesicoamniotic shunt therapy. AB - OBJECTIVES: We present a new approach to prenatal evaluation and prediction of renal function and long-term outcomes for fetuses considered candidates for in utero surgery. STUDY DESIGN: A review of 34 cases of obstructive uropathies was made, with analysis of our approach to prenatal evaluation, the predictive value of urinary electrolytes and protein analysis in identifying renal dysplasia, and the outcomes of cases with and without in utero surgical intervention. RESULTS: Ten of 11 pregnancies that were terminated had dysplasia; one female had cloacal dysgenesis. In three of eight unshunted cases megacystis resolved after vesicocentesis. Eight of 15 shunted fetuses survived. Of those predicted to have good postnatal outcome, six of six demonstrated good postnatal renal function. Of those predicted to have poor outcomes, two of two had poor postnatal renal function and dysplasia. Seven of 15 shunted fetuses died, four of four predicted to have dysplasia were confirmed, and three died of nonrenal causes. CONCLUSIONS: Our prenatal approach successfully differentiated fetuses with underlying renal dysplasia from those without irreversible damage who subsequently benefited from in utero vesicoamniotic shunt placement. PMID- 8203439 TI - Surgically treated adnexal masses in infancy, childhood, and adolescence. AB - OBJECTIVE: We retrospectively evaluated the clinical presentation and histopathologic findings of benign and malignant adnexal masses in infants, children, and adolescents. STUDY DESIGN: Between 1955 and 1992, 486 patients (aged 7 days through 20 years) with adnexal masses were surgically evaluated. RESULTS: Of 521 adnexal masses, 92% were benign, including 335 nonneoplastic and 144 of 186 (77%) neoplastic lesions. The frequency of ovarian malignancies correlated inversely with patient age. Germ cell, stromal, and epithelial malignancies accounted for 40%, 21%, and 33%, respectively, of the 42 cancers. Nonconcordance between preoperative and postoperative diagnoses was noted in 94 cases. The most common preoperative diagnosis necessitating reassignment was acute appendicitis. During the last decade of this study, ultrasonography and computed tomography missed no malignancies. CONCLUSION: Physicians who care for young girls must be familiar with the differential diagnosis of adnexal masses to advise conservative management when appropriate and surgical intervention when necessary. PMID- 8203440 TI - The Green Bay cesarean section study. III. Falling cesarean birth rates without a formal curtailment program. AB - OBJECTIVES: We observed decreases in cesarean birth rates at two Green Bay hospitals after the 1990 publication of our first cesarean section study. The purpose of this study was to determine the causes of those decreases and to see whether any outcome changes occurred with lower rates. An additional objective was to determine the perceptions of the 10 physicians regarding the determinants of cesarean birth rates. STUDY DESIGN: We compared recent cesarean birth rates (1990 to 1992) to former rates (1986 to 1988) for 10 of the 11 physicians analyzed in our previous studies. Newborn outcomes were analyzed to determine whether variations occur in comparing low to high cesarean rate physician groups. RESULTS: The total, primary, and repeat cesarean birth rates declined from 13.3% to 10.2%, 8.6% to 6.8%, and 4.7% to 3.4%, respectively, between 1986 to 1988 and 1990 to 1992. Variations in cesarean rates occurred among physicians and groups of physicians. Higher cesarean rates did not result in better perinatal outcome. Literature reports, residency training, continuing medical education attendance, and liability risks were the major determinants of cesarean birth as perceived by the 10 physicians in the study. The least important determinant, rated fifteenth of 15, was the national cesarean birth rate. PMID- 8203442 TI - Mammary stimulation test predicts preterm birth in nulliparous women. AB - OBJECTIVE: This prospective clinical trial was designed to assess the ability of the mammary stimulation test to predict preterm birth in a private nulliparous population. STUDY DESIGN: The mammary stimulation test was performed between 26 and 28 weeks' gestation by 267 nulliparous women with singleton pregnancies. Test results were blinded to both patient and referring physician. Pregnancy outcome data were collected from the perinatal database and medical records. RESULTS: The mammary stimulation test was positive in 45 of 266 (17%) patients. Delivery occurred at < 37 weeks in 27 patients (10.2%) and at < 34 weeks in five (1.9%). The mammary stimulation test demonstrated a sensitivity of 37%, a specificity of 84%, a positive predictive value of 20%, and a negative predictive value of 92% for delivery at < 37 weeks' gestation. For delivery at < 34 weeks' gestation the mammary stimulation test had a sensitivity of 60%, a specificity of 82%, a positive predictive value of 6%, and a negative predictive value 99%. The odds ratio for delivery at < 37 weeks was 3.0 (95% confidence interval 1.3, 7.1), and for delivery at < 34 weeks the odds ratio was 7.0 (95% confidence interval 1.1, 43.0). One third of preterm deliveries were secondary to idiopathic preterm labor, and the mammary stimulation test was positive in 77.8% (seven of nine) of these pregnancies. Patients with a positive test were more likely to require observation in labor and delivery for preterm uterine contractions (34% vs 4.3%, p < 0.01), and they were more likely to demonstrate change at cervical examination (14% vs 2%, p < 0.01). CONCLUSION: In this population traditionally considered to be at low risk for preterm birth a positive mammary stimulation test was useful in identifying patients at risk for preterm uterine activity and preterm birth. Equally important was the identification of women who were at low risk for preterm birth. PMID- 8203441 TI - Lack of heritability in ovarian germ cell malignancies. AB - OBJECTIVE: Our purpose was to determine whether relatives of patients with ovarian germ cell malignancies not associated with sex chromosome abnormalities are at increased risk for similar tumors. STUDY DESIGN: We reviewed pedigrees of 78 presumptive 46,XX patients (ages ranging from newborn to 20 years) with malignant ovarian germ cell tumors, excluding cases of dysgerminoma and gonadoblastoma. A three-generation family history of each proband was reviewed specifically to identify cancer in any family member. RESULTS: Seventy-eight mothers, 87 sisters, 135 aunts, and 156 grandmothers were surveyed. None had a malignant ovarian germ cell neoplasm or other malignant ovarian neoplasm. CONCLUSION: First- and second-degree relatives of probands with ovarian germ cell malignancies do not have an increased risk for similar tumors. These findings were not predicted because of the well-recognized association of hereditary tumors and early age of onset. PMID- 8203443 TI - Prospective comparison of indwelling bladder catheter drainage versus no catheter after vaginal hysterectomy. AB - OBJECTIVE: This study compares the postoperative outcomes of patients in whom indwelling bladder catheterization or no catheter was used after vaginal hysterectomy. STUDY DESIGN: One hundred women undergoing inpatient vaginal hysterectomy were randomly assigned to have an indwelling Foley catheter for 24 hours or no catheter after the procedure. Data regarding postoperative morbidity were recorded, and a clean voided urine specimen for urinalysis and culture was obtained 48 hours and 2 weeks after surgery. RESULTS: The study groups were similar with respect to demographics and surgical indications. Two patients in the catheterized group required recatheterization after the catheters were removed. None of the subjects in the no-catheter group required a catheter. There was a significantly higher incidence of fever in the catheter group. No differences were found in the incidence of positive urine cultures between the study groups at 48 hours (8 vs 14, p = 0.227) and 2 weeks (6 vs 1, p = 0.111), respectively. CONCLUSION: Indwelling catheterization appears unnecessary after routine vaginal hysterectomy. However, catheter placement for 24 hours does not contribute significantly to postoperative morbidity. PMID- 8203444 TI - First-trimester rapid semiquantitative assay for urine pregnanediol glucuronide predicts gestational outcome with the same diagnostic accuracy as serial human chorionic gonadotropin measurements. AB - OBJECTIVE: The purpose of this study was to compare a single urine pregnanediol glucuronide measurement with serial human chorionic gonadotropin titers for the prediction of abnormal early gestations. STUDY DESIGN: We analyzed multiple urine pregnanediol glucuronide levels in 19 spontaneously conceived pregnancies during the first 49 days of gestation. A semiquantitative measurement was made by rapid enzyme immunoassay (Phase Check) at different urinary dilutions. To establish the reliability of semiquantitative urine pregnanediol glucuronide assay to detect abnormal gestation, this test was compared with human chorionic gonadotropin doubling times derived from a previously described normal population. A receiver operator characteristic curve was constructed for each test, and areas under the curve with corresponding SEs were calculated. The critical-ratio z test was used to compare the two assays. RESULTS: The receiver-operator characteristic curves indicate that both urine pregnanediol glucuronide and human chorionic gonadotropin doubling can predict early gestational complications (p < 0.05). The area under the curve for human chorionic gonadotropin doubling time was 0.809 +/- 0.048, and urine pregnanediol glucuronide had an area of 0.702 +/- 0.072. Comparison of the area under the curve revealed that the ability of urine pregnanediol glucuronide to predict early gestational failure was indistinguishable from that of human chorionic gonadotropin doubling times (p > 0.05). A 1:2 dilution of urine gave the best results in the semiquantitative urine pregnanediol glucuronide test (Phase Check). CONCLUSIONS: On the basis of receiver-operator analysis, semiquantitative urine pregnanediol glucuronide measurements predict abnormal early gestations as well as serial human chorionic gonadotropin measurements do. The ability of a single urine semiquantitative assay (Phase Check) to predict early gestational complications offers a convenient screening tool that may identify women with abortive or ectopic pregnancies before the onset of symptoms. PMID- 8203445 TI - Factors relevant to mode of preterm delivery with syndrome of HELLP (hemolysis, elevated liver enzymes, and low platelets). AB - OBJECTIVE: Our purpose was to investigate factors relevant to mode of delivery for patients with preterm (< 34 weeks) gestation complicated by the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). STUDY DESIGN: The pregnancies of 189 patients with HELLP syndrome and delivery < 34 weeks' gestation between January 1980 and October 1991 were studied retrospectively. Only patients with class 1 (platelet nadir < or = 50,000 per microliter, n = 83) and class 2 (platelet nadir > 50,000 to < or = 100,000 per microliter, n = 106) HELLP syndrome were included. Maternal and perinatal factors relevant to type of delivery were reviewed. RESULTS: The incidence of cesarean delivery for all patients was 76.2% (primary rate 72.4%). Abdominal delivery occurred equally between class 1 (78.3%) and class 2 (74.5%) patients. Cesarean section was the mode of delivery for 87% of pregnancies at < 30 weeks' gestation in contrast to 68% of pregnancies at > or = 30 weeks but < 34 weeks' gestation (odds ratio 3.2, 95% confidence interval 1.4 to 7.5, p < 0.005). Indications for cesarean section included deteriorating maternal condition alone (50%), deteriorating maternal and fetal condition (27%), nonvertex fetal presentation (11.5%), and failure to progress (11%). Induction of labor was significantly more successful during the > or = 30 but < 34 weeks' pregnancy interval (47.5%) than in pregnancies at < 30 weeks (15.2%) (odds ratio 0.2, 95% confidence interval 0.1 to 0.55, p < 0.001). A trial of labor was successful in 22% of patients with an initial modified Bishop score < or = 2 versus 45% with an initial Bishop > 2 (odds ratio 0.5, 95% confidence interval 0.2 to 1.3, p = 0.16). CONCLUSION: Parturients with class 1 and 2 HELLP syndrome at < 34 weeks' gestation are at high risk for cesarean delivery. At a gestational age < 30 weeks, the likelihood of successful labor induction with vaginal delivery is remote, especially in association with an unfavorable cervix or the absence of labor. PMID- 8203446 TI - Morbidity caused by terbutaline infusion pump therapy. PMID- 8203447 TI - Preterm premature rupture of membranes: a continuing dilemma. PMID- 8203448 TI - Fetal grasping of the umbilical cord with simultaneous fetal heart rate monitoring. PMID- 8203449 TI - Obstetricians and epidural analgesia. PMID- 8203450 TI - Is toxemia of pregnancy a better concept? PMID- 8203451 TI - Loop fracture during intrauterine surgery with a gynecologic resectoscope. PMID- 8203452 TI - Intramuscular methotrexate for tubal pregnancy: failure and fertility. PMID- 8203453 TI - Chromosomal aberrations in soft tissue tumors. Relevance to diagnosis, classification, and molecular mechanisms. AB - In recent years, significant progress has been made in identifying characteristic chromosomal rearrangements associated with several solid tumor types, notably sarcomas, a relatively rare subset of human cancer. Most sarcomas analyzed have been found to be characterized by recurrent chromosome translocations that are specific to histological types. We have reviewed published reports of chromosomal aberrations in benign and malignant soft tissue tumors and found an incidence of specific translocations in these neoplasms that ranged from 20% to 93% within histological tumor types. Identification of recurrent chromosomal abnormalities in benign tumors has resulted in a reappraisal of the general concept that benign tumors have a normal (diploid) chromosome constitution. The variety of recurrent changes present in the different tumor types attests to the cytogenetic diversity inherent in these tumors. The chromosomal rearrangements in each of the tumor types were unique and did not correspond to cancer-associated aberrations known from other solid or hematopoietic malignancies. Cytogenetics thus provides an essential adjunct to diagnostic surgical pathology in the case of malignant soft tissue tumors, which often present substantial diagnostic challenges. In addition, it represents another approach to determine the histogenetic origin of some tumors and identifies sites of gene deregulation for molecular analysis. Indeed, recent molecular analyses of several sarcoma-associated translocations have identified novel genes and novel mechanisms of their dysregulation. PMID- 8203454 TI - Death at Sverdlovsk: what have we learned? PMID- 8203455 TI - HIV-1 nucleic acids localize to the spermatogonia and their progeny. A study by polymerase chain reaction in situ hybridization. AB - The purpose of this study was to determine the histological distribution of in situ polymerase chain reaction (PCR)-amplified HIV-1 nucleic acids in the male genital tract to elucidate the mechanism of sexual transmission of AIDS. Viral DNA was detected in the testicular tissue of 11 of 12 men with HIV-1 infection using the PCR in situ hybridization technique. The amplified viral DNA localized to many spermatogonia, spermatocytes, and rare spermatids. Relatively few viral infected macrophages were noted, mostly in the prostate. The viral infection was activated given the presence of cDNA sequences consistent with genomic and multiple spliced transcripts as determined by reverse transcription in situ PCR. PCR-amplified viral nucleic acids were not detected in the epithelial of the prostate, epididymis, seminal vesicles, or penis in men with AIDS nor in any genital tract tissues from three boys who died of AIDS acquired in utero. The demonstration that HIV-1 selectively infects the spermatogonia and their progeny suggests that this may serve as a primary source of venereal spread of the virus. Concomitant destruction of these cells by HIV-1 may also explain the marked inhibition of spermatogenesis and severe atrophy that characterizes the testes in AIDS. PMID- 8203456 TI - Differential effects of oral versus intrathymic administration of polymorphic major histocompatibility complex class II peptides on mononuclear and endothelial cell activation and cytokine expression during a delayed-type hypersensitivity response. AB - Oral and intrathymic exposure to antigen can each induce systemic antigen specific immune tolerance, but the mechanisms have not been well defined. We studied the effects that the route of exposure to antigen has on the mechanisms of tolerance in vivo using synthetic polymorphic class II major histocompatibility complex (MHC) peptides in a skin delayed-type hypersensitivity (DTH) response model. Lewis rats were immunized by injection in the footpad with synthetic peptides (RT1.Bu and/or RT1.Du) derived from the hypervariable domain of MHC class II beta chain of the Wistar-Furth rat in complete Freund's adjuvant and challenged 2 weeks later by injection in the ear with the MHC peptides. An "oral" group received the peptide mixture by gavage (100 micrograms/day for 5 days) 3 days before immunization, and an "intrathymic" group received a single intrathymic injection of 100 micrograms of peptides 48 hours before immunization. Oral therapy reduced the DTH response to 23 +/- 7%, and intrathymic exposure reduced the DTH response to 26 +/- 6% (P < 0.001) as compared with control DTH responses of unmodified Lewis animals. Immunohistological evaluation of DTH skin lesions showed that oral and intrathymic therapy each decreased mononuclear cell infiltration, fibrin deposition, and endothelial activation when compared with that seen in control rats. In contrast, while both protocols markedly reduced interleukin (IL-2) and interferon-gamma expression, they had differing effects on local expression of IL-4, transforming growth factor-beta, IL-2R, and CD45RC (a possible discriminant between Th1 and Th2 cells in rats). Oral therapy was associated with increased expression of IL-4 and preservation of transforming growth factor-beta expression by residual IL-2R+, CD45RC- mononuclear and endothelial cells, whereas thymic exposure suppressed essentially all features of immune activation including IL-2R induction and cytokine expression. Our data a) document the detailed pattern of cytokine expression and mononuclear and endothelial cell activation markers during DTH responses and b) confirm that oral tolerance is associated with immune deviation to a predominance of Th2 cell function, whereas intrathymic tolerance may be mediated by T-cell anergy or clonal deletion. PMID- 8203457 TI - Tumor necrosis factor-alpha mRNA expression in lipopolysaccharide-stimulated rat kidney. Chronological analysis of localization. AB - To study the time course of lipopolysaccharide-induced production of tumor necrosis factor-alpha (TNF-alpha) in the kidney, we utilized a highly sensitive non-radioisotopic in situ hybridization with 1-nm gold-conjugated anti digoxigenin for localization of TNF-alpha mRNA expression after lipopolysaccharide administration. TNF-alpha mRNA expression localized by in situ hybridization showed a peak increment in proximal tubular epithelial cells and glomeruli at 2 hours and returned to almost normal levels at 6 hours. The intensity of the signal was much stronger in proximal tubules than in glomeruli. These findings were confirmed by the demonstration of similar kinetics in the increase of TNF-alpha message, measured by using amplification of the third and fourth exons of TNF-alpha gene by reverse transcription-polymerase chain reaction of microdissected proximal tubular segments and isolated glomeruli. Reverse transcription-polymerase chain reaction of cultured rat mesangial and glomerular epithelial cells demonstrated that mesangial cells, not glomerular epithelial cells, were responsible for the observed glomerular signals. PMID- 8203458 TI - Latent infection induced with cottontail rabbit papillomavirus. A model for human papillomavirus latency. AB - Latent human papillomavirus infection, a very common event, is most likely the source of primary and recurrent papillomas of the respiratory and genital tracts and might also be the source of neoplastic lesions of the female genital tract and the penis. We have developed a simple model for papillomavirus latency using cottontail rabbit papillomavirus. Skin of domestic rabbits was minimally scarified and inoculated with dilutions of a crude virus suspension ranging from 200 ng to 20 pg viral DNA per inoculated site. Dilution of virus to less than 10 ng/site resulted in delayed and reduced efficiency of inducing warts. After follow-up of 1 to 6 months, sites immediately adjacent to papillomas and inoculated sites where papillomas did not form were biopsied and analyzed by Southern blot and polymerase chain reaction. Inoculated tissues that were clinically and histologically normal contained viral DNA at low levels, detectable by polymerase chain reaction. Ability of the latent virus to induce warts was confirmed by activation with mild skin irritation causing wart formation. This simple model system for latent papillomavirus can be used to study mechanisms of viral activation, therapies to prevent activation, and therapies to eliminate latent virus and thus cure the infection. PMID- 8203459 TI - Apolipoprotein E4 and beta amyloid in senile plaques and cerebral blood vessels of aged rhesus monkeys. AB - Recent studies of late onset familial and sporadic Alzheimer's disease (AD) show a genetic disequilibrium between inheritance of the epsilon 4 allele of the apolipoprotein E (ApoE) gene and development of AD. beta-Amyloid (A beta) positive senile plaques and blood vessels in AD are immunoreactive for ApoE, suggesting that ApoE plays a role in amyloid deposition. We examined the brains of nine rhesus monkeys (Macaca mulatta) to determine the immunohistochemical distribution of ApoE and to investigate the association of ApoE with A beta in this species. Antibodies to ApoE and A beta labeled senile plaques and vessels in the brains of aged monkeys, indicating cross-species homogeneity of the association of these two proteins. Polymerase chain reaction/restriction enzyme analysis of the ApoE epsilon 3/epsilon 4 allelic site (residue 112) in the rhesus monkey revealed that the rhesus has an arginine at this site like the human epsilon 4 allele, the cynomolgus monkey, baboon, cow, pig, mouse, and rat but unlike the human epsilon 3 allele and the rabbit. These results emphasize the value of aged nonhuman primates as animal models for A beta deposition and ApoE4 A beta interactions in AD and aging. PMID- 8203460 TI - Bcl-2 expression in normal endometrium during the menstrual cycle. AB - Bcl-2 is a proto-oncogene initially described in the (14;18) translocation in follicular lymphoma. It has been shown to prolong cell survival by preventing apoptosis. Endometrium undergoes rapid proliferation and differentiation under hormone control and is thus an excellent model to study the hormone dependency of Bcl-2 expression. We studied Bcl-2 expression by an immunohistochemical method in 53 samples of normal endometrium randomly distributed throughout the menstrual cycle, as well as five samples of hyperplastic endometrium. Bcl-2 staining predominated in glandular cells and peaked at the end of the follicular phase. Bcl-2 expression disappeared at the onset of secretory activity. The stroma, surface lining epithelium and arterial vessels also displayed cyclic variations in Bcl-2 expression. These results strongly suggest hormone-dependent regulation of Bcl-2 expression, which could play an important role in tumorigenesis. PMID- 8203461 TI - Comparative genomic hybridization of human malignant gliomas reveals multiple amplification sites and nonrandom chromosomal gains and losses. AB - Nine human malignant gliomas (2 astrocytomas grade III and 7 glioblastomas) were analyzed using comparative genomic hybridization (CGH). In addition to the amplification of the EGFR gene at 7p12 in 4 of 9 cases, six new amplification sites were mapped to 1q32, 4q12, 7q21.1, 7q21.2-3, 12p, and 22q12. Nonrandom chromosomal gains and losses were identified with overrepresentation of chromosome 7 and underrepresentation of chromosome 10 as the most frequent events (1 of 2 astrocytomas, 7 of 7 glioblastomas). Gain of a part or the whole chromosome 19 and losses of chromosome bands 9pter-23 and 22q13 were detected each in five cases. Loss of chromosome band 17p13 and gain of chromosome 20 were revealed each in three cases. The validity of the CGH data was confirmed using interphase cytogenetics with YAC clones, chromosome painting in tumor metaphase spreads, and DNA fingerprinting. A comparison of CGH data with the results of chromosome banding analyses indicates that metaphase spreads accessible in primary tumor cell cultures may not represent the clones predominant in the tumor tissue. PMID- 8203462 TI - Epstein-Barr virus (EBV) infects T lymphocytes in childhood EBV-associated hemophagocytic syndrome in Taiwan. AB - We have reported the prevalence of a fulminant hemophagocytic syndrome (HS) in previously healthy young children in Taiwan, most of which probably represent a lethal form of primary or active Epstein-Barr virus (EBV) infection. To further confirm their EBV association, in situ EBV hybridization (ISH) was performed on tissue biopsies from 15 pediatric HS patients (median age, 3 years and 4 months) using digoxigenin-labeled RNA probes EBER1. Double labeling immunostaining and ISH was then performed to define the immunophenotype of the lymphoid cells containing the EBV transcripts. Among the 13 patients who had serological evidence of acute or active EBV infection, 9 had demonstrable EBER1 transcripts in bone marrow, liver, and/or skin biopsies. EBER1-specific signal was not detectable in the two specimens from EBV-seronegative patients. The distribution of EBV-containing cells could be extensive or scattered. To our surprise, the EBER1 transcripts existed exclusively in T lymphoid cells in all nine cases examined rather than in B cells as previously believed in infectious mononucleosis. Considering the young affected age of the HS patients and the serological response to EBV, we suggest that EBV can infect T cells in primary EBV infection and the proliferation of these EBV-infected T cells may be responsible for the ominous outcome in childhood HS patients in Taiwan. PMID- 8203463 TI - Early stages of simian immunodeficiency virus infection in lymph nodes. Evidence for high viral load and successive populations of target cells. AB - Lymph nodes obtained from 14 macaques sacrificed at early time points following experimental inoculation with simian immunodeficiency virus were analyzed by in situ hybridization for virus load and virus cellular tropism. The lymph nodes presented a remarkably high viral load during the early phase of infection, as viral RNA was detected in as many as 2% of lymph node cells 1 week after inoculation. At this stage, macrophages and T4 lymphocytes were identified by combined immunohistochemistry and in situ hybridization as the target cells of the virus. Simian immunodeficiency virus-positive macrophages concentrated in the subcapsular sinuses, suggesting an entry of infected cells via the afferent lymphatics. A shift in the pattern of viral infection was observed at 2 weeks after inoculation, with a concentration of viral RNA in the germinal centers of the developing lymphoid follicles. Follicular dendritic cells were found to be the major target of the virus at this stage. Follicular dendritic cells were associated with high levels of viral RNA but little or no detectable viral DNA, suggesting that the virus was present mostly in the form of viral particles trapped at the cell surface. Follicular dendritic cell-associated virus persisted at high levels for 2 months before subsiding, indicating that follicular dendritic cells constituted a major reservoir of the virus during the early stages of simian immunodeficiency virus infection. PMID- 8203464 TI - An analysis of the expression of cyclophilin C reveals tissue restriction and an intriguing pattern in the mouse kidney. AB - Cyclophilin C (cyp C) is a cyclosporin A (CsA) binding protein originally isolated from a mouse bone marrow stromal cell line. We have compared the expression patterns of the mammalian cyclophilins A, B, and C in mouse tissues using in situ hybridization. These studies reveal that cyp C is expressed in a restricted subset of tissues including mouse ovary, testis, bone marrow, and kidney. Within the kidney, cyp C is highly expressed in a narrow zone in the outer medulla. Using monoclonal antibodies reactive against cyp C, we find that the kidney cells expressing cyp C correspond to the S3 segment of the nephron. The S3 segment has been shown to sustain histopathological damage from high dosages of CsA, raising the possibility that cyp C may be involved in mediating this damage. PMID- 8203465 TI - A unique rat model of bile ductular hyperplasia in which liver is almost totally replaced with well-differentiated bile ductules. AB - A novel rat model was developed in which furan combined in a unique synergistic manner with bile duct ligation to induce replacement of most of liver with well differentiated hyperplastic bile ductules. Multiple tissue sections of liver from Fischer 344 male rats first subjected to a bile duct ligation and 1 week later given furan by gavage at 45 mg/kg body weight, once a day, five times weekly for 5 to 6 weeks, exhibited a mean percent of bile ductule tissue per total liver section area of 72.6 +/- 16.3% compared to control values of 20.0 +/- 4.2% for bile duct-ligated rats that received corn oil by gavage instead of furan and 11.9 +/- 3.1% for rats that were given a sham operation followed by furan. This dramatic difference was also reflected by the very high mean gamma-glutamyl transpeptidase specific activity of liver homogenates from the bile duct ligated/furan-treated rats, which was approximately 8 x 10(3) nmoles p nitroaniline/mg protein/hour versus values of approximately 2 x 10(3) for bile duct-ligated/corn oil control, approximately 1 x 10(3) for sham-operated/furan treated control, and 44.9 for untreated rat. The data presented support a potentially powerful experimental model for investigating bile ductular cell functions, differentiation, and proliferation. PMID- 8203466 TI - Plasminogen activation in healing human wounds. AB - Tissue injury is followed by formation of a provisional, fibrin-containing matrix. It is later on replaced by granulation tissue. Replacement involves extracellular proteolysis by fibrinolytic enzymes. Plasmin is a fibrinolytic proteinase and is generated from ubiquitous plasminogen by cell-derived urokinase type (uPA) or tissue-type (tPA) plasminogen activator. To explore the cells and components involved in plasminogen activation, we have performed a combined immunohistological and zymographic study on human skin wounds produced iatrogenically by debridement. The fibrin(ogen)-specific staining indicated the progressive removal of a fibrin-containing provisional matrix. Plasmin(ogen) was present over the entire observation period. It was diffusely distributed and also displayed a conspicuous association with cells of the granulation tissue, in particular with monocytes/macrophages and fibroblasts. Also, uPA was associated with monocytes/macrophages and fibroblasts, whereas the uPA-receptor (uPA-R) was stained in monocytes/macrophages only. The uPA was potentially active as indicated by zymography. No tPA-specific staining was found. The findings point at the importance of monocytes/macrophages and fibroblasts in uPA-mediated plasminogen activation in healing human skin wounds. PMID- 8203467 TI - Fragmentation of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis (ALS). Clinical studies in ALS of Guam and experimental studies in deafferented neurons and in beta,beta'-iminodipropionitrile axonopathy. AB - Previous morphological immunoenzymatic studies with organelle-specific antibodies have disclosed an apparent fragmentation of the Golgi apparatus in large numbers of motor neurons in 12 cases of sporadic, non-Guamanian amyotrophic lateral sclerosis (ALS) in three cases of other types of motor neuron disease and in one case of a mitochondrial myopathy with cytochrome c oxidase deficiency. Motor neurons with fragmented Golgi apparatus were moderately atrophic; in these cells, discrete immunostained elements of the organelle were twice as many as in normal neurons, and the size of each Golgi element and the percentage of the cytoplasmic area occupied by the Golgi apparatus were reduced (Am J Pathol 1992, 140: 731 737). In this report we have confirmed the fragmentation of the organelle of motor neurons in the spinal cord in six sporadic cases of Guamanian ALS. In four of the six cases the clinical course was 1 to 2 years. The percentages of motor neurons with fragmented Golgi apparatus varied from 38 to 92. Motor neurons from three additional cases of Guamanian ALS of clinical duration from 5 to 7 years did not show fragmentation of the Golgi apparatus. In two cases of Guamanian ALS and in one non-Guamanian ALS, all neurons with ubiquitin-positive skein-like or granular inclusions believed to be pathognomonic for ALS had fragmented Golgi apparatus. To examine whether the fragmentation of the Golgi apparatus results from reactions to either neuronal deafferentation or to lesions of proximal axons, we conducted two experimental studies. In the first study, we examined in cats the Golgi apparatus of deafferented neurons of the dorsal lateral geniculate nucleus. In the second study, we examined the Golgi apparatus of motor neurons in the spinal cord of rats with proximal axonopathy induced by beta,beta' iminodipropionitrile. In these two experiments, the neuronal Golgi apparatus studied by immunoenzymatic techniques and morphometry, was not fragmented. Taken together, the results of these studies strongly suggest that the fragmentation of the Golgi apparatus of motor neurons in ALS represents an important and perhaps early change of the organelle that may be involved in the pathogenesis of ALS. The fragmentation of the Golgi apparatus of motor neurons is a fairly specific and easily recognizable marker of ALS and may be used together with other criteria for comparisons between the human disease and proposed animal models of the disorder. PMID- 8203468 TI - Mechanisms of transthyretin amyloidogenesis. Antigenic mapping of transthyretin purified from plasma and amyloid fibrils and within in situ tissue localizations. AB - Transthyretin (TTR) is the major amyloid fibril protein in senile systemic amyloidosis and in several forms of familial amyloidoses. However, the internal organization of the fibrils is virtually unknown. It is not known whether the structure of the TTR molecules is substantially altered within the fibrils. In this study we used various antigenic mapping procedures to determine whether major antigenic sites differ between normal TTR, ATTR (TTR from amyloid fibrils), and in situ amyloid fibrils. Antigenic mapping was achieved using standard immunological procedures (ie, ELISA, Western blot, and immunohistochemistry), synthetic peptides of the TTR molecule, antisera against these synthetic peptides and against normal TTR, ATTR, and alkali-degraded amyloid fibrils. Our results show that the antigenic sites on normal plasma TTR include the AB loop and the CD loop. The amino acid sequences associated with these loops are present on the outside of the TTR molecule. Antiserum against beta-strand H reacted only with TTR in amyloid fibrils and ATTR but not with normal plasma TTR or TTR in the islets of Langerhans. Our results suggest that there is an altered configuration of TTR within amyloid fibrils when compared with plasma TTR. PMID- 8203469 TI - Analysis of alterations of oncogenes and tumor suppressor genes in chronic lymphocytic leukemia. AB - B cell chronic lymphocytic leukemia (B-CLL) represents the most frequent adult leukemia in the Western world. The molecular pathogenesis of B-CLL is largely unknown. Although initial reports on small panels of cases had suggested a role for Bcl-1 and Bcl-2 oncogene activation in B-CLL, later investigations failed to confirm these data. Among tumor suppressor genes, p53 mutations have been reported in a fraction of cases. In this study, we have attempted a conclusive definition of the involvement of dominantly acting oncogenes (Bcl-1 and Bcl-2) and tumor suppressor loci (p53, 6q-) in 100 cases of B-CLL selected for their CD5 positivity and Rai's stage (0 to IV). Rearrangements of Bcl-1 and Bcl-2 and deletions of 6q and 17p were analyzed by Southern blot using multiple probes. Mutational analysis (single strand conformation polymorphism and polymerase chain reaction direct sequencing) was used to assay p53 inactivation. No alterations of Bcl-1 or Bcl-2 were detected in the 100 cases tested. Mutations of p53 were found in 10/100 cases without any significant association with clinical stage. Deletions of 6q were present in 4/100 cases. Overall, our data indicate that: 1) contrary to previous reports, Bcl-1 and Bcl-2 rearrangements are not involved in CD5+ B-CLL pathogenesis and 2) p53 mutations are present in 10% of cases at all stages of the disease. PMID- 8203470 TI - Interstitial nephritis in Aleutian mink disease. Possible role of cell-mediated immunity against virus-infected tubular epithelial cells. AB - Aleutian mink disease (AD) has been characterized by immune complex glomerulonephritis associated with persistent infection of Aleutian mink disease parvovirus (ADV). Histopathological examination of kidneys from ADV-infected mink in this study revealed that interstitial nephritis characterized by prominent damage of renal tubuli and lymphocyte infiltration was also common in AD along with glomerulonephritis. By using strand-specific in situ molecular hybridization technique, replication of ADV was observed in tubular epithelial cells, in addition to epithelial cells of Bowman's capsules and some glomerular cells of the infected mink. Analysis of tubular lesions by a combination of immunohistochemistry and in situ hybridization revealed that the renal tubuli positive for virion DNA or replicative form DNA/mRNA of ADV were also positive for an activation marker of immunocompetent cells, which is shared by B lymphocytes and thymic epithelial cells. Infiltration of a subpopulation of T lymphocytes around infected renal tubuli were observed but deposition of immune complexes in these tubular lesions was not demonstrable. ADV replication in epithelial cells of renal tubuli and cell-mediated immune responses to the infected epithelial cells may play a role in the pathogenesis of interstitial nephritis in Aleutian mink disease. PMID- 8203471 TI - Triple drug immunosuppression significantly reduces immune activation and allograft arteriosclerosis in cytomegalovirus-infected rat aortic allografts and induces early latency of viral infection. AB - The effect of triple drug immunosuppression (cyclosporine A 10 mg/kg/day+methylprednisolone 0.5 mg/kg/day+azathioprine 2 mg/kg/day) on rat cytomegalovirus (RCMV)-enhanced allograft arteriosclerosis was investigated applying WF (AG-B2, RT1v) recipients of DA (AG-B4, RT1a) aortic allografts. The recipients were inoculated intraperitoneally with 10(5) plaque-forming units of RCMV 1 day after transplantation or left noninfected. The grafts were removed on 7 and 14 days, and at 1, 3, and 6 months after transplantation. The presence of viral infection was demonstrated by plaque assays, cell proliferation by [3H]thymidine autoradiography, and vascular wall alterations by quantitative histology and immunohistochemistry. Triple drug immunosuppression reduced the presence of infectious virus in plaque assays and induced early latency of viral infection. It significantly reduced the peak adventitial inflammatory response (P < 0.05) and reduced and delayed intimal nuclear intensity and intimal thickening (P < 0.05) in RCMV-infected allografts. The proliferative response of smooth muscle cells was reduced by triple drug immunosuppression to 50% of that observed in nonimmunosuppressed RCMV-infected allografts, but still the proliferative peak response was seen at 1 month. Only low level immune activation, ie, the expression of interleukin-2 receptor (P < 0.05) and MHC class II, was observed under triple drug immunosuppression in the adventitia of RCMV-infected allografts, whereas there was no substantial change in the phenotypic distribution of inflammatory cells. In conclusion, although RCMV infection significantly enhances allograft arteriosclerosis also in immunosuppressed allografts, triple drug immunosuppression has no additional detrimental effect but rather a protective one on vascular wall histology. These results further suggest that RCMV-enhanced allograft arteriosclerosis may be an immunopathological condition linked to the host immune response toward the graft and/or the virus rather than a direct virus-induced phenomenon. PMID- 8203472 TI - Smooth muscle cell expression of extracellular matrix genes after arterial injury. AB - Accumulation of extracellular matrix (ECM) after arterial injury is an important event in the development of intimal thickening and is modulated by heparin. To investigate the regulation of matrix protein expression, we have analyzed messenger RNA levels by Northern blotting for various ECM proteins in the rat carotid artery balloon injury model. RNA was extracted from normal arteries and from intima-medial preparations at 2 days, 1 week, 2 weeks, and 4 weeks after balloon injury of arteries in animals receiving either saline or heparin infusion. Transcripts for the heparan sulfate proteoglycans perlecan, syndecan, and ryudocan; the chondroitin sulfate proteoglycan versican; the dermatan sulfate proteoglycan biglycan; type I procollagen; and tropoelastin all were increased on Northern blots beginning at 1 week after injury. By in situ hybridization, the transcripts for elastin nd biglycan were primarily localized to smooth muscle cells in the intima and were diminished by heparin in proportion to the decrease in intimal mass. Other matrix genes (perlecan, ryudocan) were expressed in the intima and media and were not affected by heparin. The results support the conclusion that ECM gene expression is a relatively late event in the response of the carotid artery, and that some of the genes are expressed only in the intima whereas others are expressed in both the intima and media. PMID- 8203473 TI - Granulophysin is located in the membrane of azurophilic granules in human neutrophils and mobilizes to the plasma membrane following cell stimulation. AB - Granulophysin, a protein described in platelet dense granule membranes, has been shown to be similar or identical to CD63, a lysosomal membrane protein. We have previously shown granulophysin to be present in neutrophils using immunofluorescence. We now localize granulophysin to the neutrophil azurophilic granules by fine structural immunocytochemistry. Granulophysin expression on the surface membrane of the neutrophil is increased following stimulation of the cells, demonstrated by flow cytometry and fine structural immunocytochemistry. A similar pattern is shown for an anti-CD63 antibody. Incubation of activated neutrophils with D545, a monoclonal antibody to granulophysin, blocks subsequent binding of anti-CD63 antibodies to the cell surface, and anti-CD63 antibodies prevent subsequent binding of D545 as assessed by flow cytometry and immunoblotting. Our results support the homology of CD63 and granulophysin previously demonstrated in platelets and confirm CD63 as an activation marker in neutrophils and the first azurophilic granule membrane marker of neutrophils. PMID- 8203474 TI - The role of macrophage colony-stimulating factor in hepatic glucan-induced granuloma formation in the osteopetrosis mutant mouse defective in the production of macrophage colony-stimulating factor. AB - To elucidate the effects of macrophage colony-stimulating factor (M-CSF) on Kupffer cells and monocyte/macrophages in hepatic granuloma formation, we examined granulomas produced by glucan injection in the liver of osteopetrotic mice and littermates with or without M-CSF administration. In the osteopetrotic mice, monocytes were deficient in peripheral blood, and their number did not increase after glucan injection. Hepatic granulomas were formed in the osteopetrotic mice by glucan injection without a supply of blood monocytes. During this process, M-CSF-independent Kupffer cells proliferated, particularly before the granuloma formation, clustered in the hepatic sinusoid, and transformed into epithelioid cells and multinuclear giant cells. In the M-CSF treated osteopetrotic mice, glucan injection induced an increase in the number of blood monocytes and formed hepatic granulomas at a nearly similar degree to that of littermate mice. Thus, it is concluded that neither monocytes nor M-CSF are necessary for granuloma formation. In contrast, Kupffer cells play a crucial role as granulomas develop in M-CSF-uninjected osteopetrotic mice. PMID- 8203475 TI - Lung lymphatics increase after hyperoxic injury. An ultrastructural study of casts. AB - The microscopic lymphatics of the lung can be cast and studied with scanning electron microscopy. This technique shows several different forms of lymphatics and the interstitial space that leads into lymphatics as no other method can. To study changes in lymphatic forms, rats were placed in 85% oxygen for 7 days to produce pulmonary edema. Methyl methacrylate resin was injected into the lung vasculature at various times after the animals were removed from hyperoxia. In the animals not exposed to hyperoxia, no artery, vein, or airway was surrounded by a lymphatic cast. However, in rats that were in the hyperoxic chamber, 22% of arteries, 30% of veins, and 51% of indeterminate blood vessels (which could be arteries or veins) were encompassed by saccular lymphatic casts. These lymphatics were still observed 7 days after recovery from hyperoxia. Fourteen days after hyperoxia, the lymphatics returned to control values. Only 9% of the pleural surface of the animals not exposed to hyperoxia had initial lymphatics. Fifty-two percent of the hyperoxia-exposed animals had initial lymphatics, measured 3 days after exposure. This decreased to 14% 14 days after exposure to hyperoxia (P < 0.01). Conduit lymphatics were found on the pleural surfaces of 33% of animals exposed to ambient air and 100% of animals exposed to the high-oxygen environment (P < 0.05). The median percentage of the pleural surface covered with lymphatics was 0 in the animals exposed to ambient air. It was 65% in animals exposed to hyperoxia, 3 days after returning to room air. It was again 0 in animals exposed to hyperoxia, 14 days after returning to room air (P < 0.001). The lymphatics around veins expanded more than around arteries (P < 0.0001). These results indicate that in the rat all compartments of the lung lymphatics expand after the injury and edema caused by oxygen and return to normal with the resolution of the edema. PMID- 8203476 TI - Myocardial changes in acute Trypanosoma cruzi infection. Ultrastructural evidence of immune damage and the role of microangiopathy. AB - Histological and ultrastructural studies of the hearts of dogs sacrificed 18 to 26 days after intraperitoneal inoculation with 4 x 10(5) blood forms of the 12 SF strain of Trypanosoma cruzi/kg of body weight disclosed myocarditis characterized by parasitic invasion of some myocytes, damage and necrosis of nonparasitized myocytes, and interstitial infiltration by mononuclear cells. Nonparasitized myocytes showed alterations ranging from mild edema to severe myocytolysis. These changes often were accompanied by contacts of myocytes with lymphocytes (both granular and agranular) and macrophages. These contacts were characterized by focal loss of the myocyte basement membrane and close approximation of the plasma membranes of the two cells. Contacts between lymphocytes and capillary endothelial cells were also frequent. Platelet aggregates and fibrin microthrombi were observed in some capillaries. Our findings suggest that immune effector cells play a major role in the pathogenesis of the myocyte damage and the microangiopathy in acute Chagas' disease. PMID- 8203478 TI - What is TUF? PMID- 8203477 TI - Feline Niemann-Pick disease type C. PMID- 8203479 TI - Viral gene products and replication of the human immunodeficiency type 1 virus. AB - The acquired immunodeficiency syndrome (AIDS) epidemic represents a modern-day plague that has not only resulted in a tragic loss of people from a wide spectrum of society but has reshaped our viewpoints regarding health care, the treatment of infectious diseases, and social issues regarding sexual behavior. There is little doubt now that the cause of the disease AIDS is a virus known as the human immunodeficiency virus (HIV). The HIV virus is a member of a large family of viruses termed retroviruses, which have as a hallmark the capacity to convert their RNA genome into a DNA form that then undergoes a process of integration into the host cell chromosome, followed by the expression of the viral genome and translation of viral proteins in the infected cell. This review describes the organization of the HIV-1 viral genome, the expression of viral proteins, as well as the functions of the accessory viral proteins in HIV replication. The replication of the viral genome is divided into two phases, the early phase and the late phase. The early phase consists of the interaction of the virus with the cell surface receptor (CD4 molecule in most cases), the uncoating and conversion of the viral RNA genome into a DNA form, and the integration into the host cell chromosome. The late phase consists of the expression of the viral proteins from the integrated viral genome, the translation of viral proteins, and the assembly and release of the virus. Points in the HIV-1 life cycle that are targets for therapeutic intervention are also discussed. PMID- 8203481 TI - Differential Ca2+ sensitivities of BK(Ca) isochannels in bovine mesenteric vascular smooth muscle. AB - The planar bilayer method was used to characterize the properties of large Ca(2+) activated K+ [BK(Ca)] channels of smooth muscle from bovine mesenteric arteries. We found two isochannels of BK(Ca), differing in sensitivity to Ca2+ on the intracellular side of the channel. The first isochannel, Kc1, had a single channel conductance of 287 +/- 8 pS and required a potential of -33 mV to activate to an open probability (Po) of 0.5 with 1 microM Ca2+. The single channel conductance of the second isochannel, Kc2 (282 +/- 8 pS), was not statistically different from that of Kc1 but required a potential of 41 mV to activate to a Po of 0.5 with 1.0 microM Ca2+. At a channel voltage of 0 mV, the Ca2+ concentrations for activating Po to 0.5 were 0.2 and 10 microM for Kc1 and Kc2, respectively. The equivalent gating charges, estimated from the Boltzmann equation, were 2.4 and 2.2 for Kc1 and Kc2, respectively. The K/Cl selectivity of Kc1 was > 40 and not significantly different from Kc2. The Po of either isochannel did not change when protein kinase A or alkaline phosphatase was added to the intracellular side. We conclude that bovine mesenteric arteries contain two distinct isochannels of BK(Ca) that differ in Ca2+ sensitivity but are identical with respect to single-channel conductance, equivalent gating charge, and K+/Cl- selectivities. PMID- 8203480 TI - Decline in number of Na-K pumps on low-K+ sheep reticulocytes during maturation is modulated by Lp antigen. AB - The number of the Na-K pumps on sheep red blood cells declines markedly during cell maturation. In addition, in red blood cells of the low-K+ (LK) phenotype, there is an increase during maturation in the affinity of the pumps for intracellular K+. This increase does not occur in cells of the high-K+ (HK) phenotype. This HK/LK polymorphism is associated with the M/L blood group antigen system. The Lp antigen, which is on only LK cells, promotes the increase in affinity for K+ [Am. J. Physiol. 265 (Cell Physiol. 34): C99-C105, 1993]. Mature LK cells have fewer pumps than mature HK cells. The present study shows that the Lp antigen also promotes the loss of pumps in LK cells. The evidence was that modification of the Lp antigen of immature LK red blood cells either with anti-Lp antibody or by trypsinization diminished the loss of pumps during culture in vitro (numbers determined from [3H]ouabain binding). Confirmation came from demonstration of the decline during maturation of the amount of the alpha-subunit of the Na-K pump (measured by immunoblotting), which was also retarded by pretreatment with anti-Lp or trypsin. Comparisons of the relative amounts of Lp antigen on immature and mature LK cells showed that there is little decline in number of antigens during maturation. Therefore there is an increase in the antigen-to-pump ratio during maturation even though an association between pumps and antigens is necessary for the loss of pumps. PMID- 8203482 TI - Skeletal muscle overload upregulates the sarcoplasmic reticulum slow calcium pump gene. AB - Functional data suggest that the kinetics of force production and relaxation are slowed in hypertrophied skeletal muscle because of chronic overload. The purpose of this study was to determine whether gene expression of the slow/cardiac isoform of the sarcoplasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (ATPase) pump is upregulated in overloaded fast-twitch plantaris muscles. Increased active muscle loading was induced in rat plantaris muscles bilaterally by surgical removal of gastrocnemius and soleus muscles. Mass of the plantaris muscle was 80% greater 5 wk after surgery than in age-matched unoperated control rats (P < 0.05). Expression of the slow pump mRNA was 135% greater in hypertrophied muscles, as determined from autoradiograms of Northern blots with use of a cDNA probe specific for the slow/cardiac isoform. A monoclonal antibody (7E6) was used to quantify slow Ca2+ pump in SR vesicles with use of Western blot analysis. Densitometry of blots showed that the relative expression of the slow pump protein was 130% greater in hypertrophied plantaris muscles. Expression of the fast SR Ca2+ pump protein isoform, assessed using monoclonal antibody A52, was 25% less in hypertrophied than in control muscles. The Ca2+ uptake rate and ATPase activity of SR vesicles was approximately 15% lower in hypertrophied plantaris muscles (P < 0.05). Differential phospholamban expression could not account for changes in SR Ca2+ handling, because it could not be detected in rat slow- or fast-twitch skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203483 TI - Identification and characterization of the rat intestinal epithelial cell (IEC 18) interleukin-1 receptor. AB - Interleukin-1 (IL-1), an important mediator of inflammation, may act in chronic inflammatory disorders of the intestine such as idiopathic inflammatory bowel diseases. Although the IL-1 receptor (IL-1R) has been studied extensively in many cell lines, including T cells, B cells, and fibroblasts, it has not been demonstrated on intestinal epithelial cells. IL-1 affects intestinal epithelial cell proliferation in vitro, suggesting the presence of IL-1Rs on intestinal epithelium. This paper demonstrates and further characterizes an IL-1R in a rat intestinal epithelial cell. Cells from rat intestinal epithelial cell line IEC-18 were grown to confluence in six-well plates, and association studies with 125I labeled IL-1 beta to determine specific binding and equilibrium conditions were performed. A competitive-inhibition curve verified the IL-1 concentration required to saturate the IL-1R, and a Scatchard plot revealed a dissociation constant (Kd) of 1.2 x 10(-10) M, with 1,000 receptors per epithelial cell. Binding studies using increasing concentrations of 125I IL-1 beta alone confirmed the receptor density. Cross-linking 125I-IL-1 beta to the IEC-18 IL-1R demonstrated an IL-1R of approximately 80.5 kDa. cDNA transcribed from IEC-18 mRNA was used as a template for amplification of a segment of the IL-1R using complementary oligonucleotides. The resulting sequence of the IL-1R demonstrated a high degree of homology with both the human and mouse type I IL-1R.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203484 TI - Beta-adrenoceptor activation shows high-frequency fatigue in skeletal muscle fibers of the rat. AB - The effect of terbutaline (a beta 2-adrenergic agonist) on high-frequency fatigue (HFF) was studied in small bundles of rat soleus muscle fibers. HFF, the decline in force during continuous stimulation (50 Hz for 20 s), was reduced by 10-20% with 10 microM terbutaline. A similar reduction in HFF with 2 mM dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) implicated adenosine 3',5'-cyclic monophosphate (cAMP) as the second messenger in the terbutaline effect. Sodium (Na-K)-pump inhibition with 1 mM ouabain depressed peak tetanic force but did not significantly alter either the subsequent fatigue or the effect of terbutaline on fatigue. This suggested that the pump was neither rate limiting in HFF nor involved in the terbutaline effect. Nevertheless, a significant hyperpolarization recorded with terbutaline implied that beta 2-adrenoceptor activation stimulated the Na-K pump at rest. Caffeine (1 mM) slowed HFF and prevented additional effects with terbutaline. Caffeine is known to potentiate Ca2+ release from the sarcoplasmic reticulum (SR), and we suggest that terbutaline, acting via cAMP, facilitates Ca2+ release from the SR to better maintain myoplasmic Ca2+ concentration during continuous tetanic stimulation. PMID- 8203485 TI - Ion transport asymmetry and functional coupling in bovine pigmented and nonpigmented ciliary epithelial cells. AB - The solute and water transport properties of the bovine ciliary epithelium were studied using isolated pigmented (PE) and nonpigmented (NPE) cells. It was shown that these cells were functionally coupled by demonstrating dye diffusion between paired PE and NPE cells after microinjection of lucifer yellow. Electronic cell sizing was used to measure cell volume changes of isolated PE and NPE cells in suspension after anisosmotic perturbations and after transport inhibition under isosmotic conditions. The PE cells showed the presence of a regulatory volume increase when subjected to osmotic shrinkage with NaCl, whereas the NPE cells did not demonstrate a regulatory volume increase under these conditions. In contrast, the NPE cells exhibited a regulatory volume decrease when subjected to osmotic swelling, whereas the PE cells did not recover from swelling. The regulatory volume decrease in NPE cells was inhibited by increased bath K or pretreatment with quinine (1 mM). The presence of a bumetanide-sensitive mechanism capable of moving measurable amounts of solute and water, probably Na-K-2Cl cotransport, was demonstrated in the PE cells but absent in the NPE cells. Bumetanide produced a dose-dependent shrinkage of PE cells at concentrations as low as 1 microM. Isosmotically reducing bath Cl, Na, or K concentration caused a rapid shrinkage of PE cells that was bumetanide inhibitable. The asymmetry of transport properties in PE and NPE cells supports a functional syncytium model of aqueous humor formation (39) across the two layers of the ciliary epithelium wherein ion uptake from the blood is carried out by the PE cells and ion extrusion by the NPE cells. Gap-junction coupling between the cells allows the ions taken up by the PE cells to move into the NPE cells. Extrusion of Na by the Na-K pump across the aqueous facing (basolateral) membranes of the NPE cells, most likely accompanied by Cl, determines the formation of the aqueous humor. PMID- 8203486 TI - Loss of glucose transporters is an early event in differentiation of HD3 cells. AB - The HD3 cell, a chicken erythroblast cell line infected with a temperature sensitive avian erythroblastosis virus, becomes committed to differentiate to an erythrocyte upon temperature shift in presence of inducers. Before induction, the HD3 cell transports glucose and 2-deoxyglucose (2-DG). 3-O-methylglucose is poorly taken up. Upon induction of differentiation, glucose and 2-DG transport activity fall. Twenty-four hours postinduction, up to 75% of the glucose transport activity may disappear. By use of cDNA probes for chicken glucose transporters, two species of mRNA of 3.1 and 1.7 kb (equivalent to mammalian GLUT1 and GLUT3 mRNA, respectively) are detected. Both messages virtually disappear within 48 h after induction. Run-on assays show the cessation of synthesis of the corresponding RNAs parallel to the loss of glucose transport. In contrast to the glucose transporters, the nucleoside transporter level increases after induction of hematopoiesis. This developmental pattern is consistent with earlier studies showing that mature chicken erythrocytes have little glucose transport activity but retain appreciable levels of the nucleoside transporter and that nucleosides and glutamine provide major sources of oxidizable carbon compounds to sustain metabolism in circulating chicken erythrocytes. PMID- 8203487 TI - Gene expression during phorbol ester-induced differentiation of cultured human megakaryoblastic cells. AB - Platelet protein makeup is determined during transformation of megakaryoblasts to mature megakaryocytes, the immediate precursor of circulating platelets. To better understand the molecular mechanisms of megakaryocyte formation, gene expression was characterized by Northern analysis and RNA fingerprinting of cultured human CHRF-288 megakaryoblastic cells undergoing phorbol ester stimulated megakaryocytic differentiation or serum-stimulated megakaryoblast proliferation. Protooncogenes c-fos and c-jun were coordinately upregulated in both proliferating and differentiating cells, whereas c-myc transcripts were upregulated during proliferation only. In contrast, mRNAs for transforming growth factor-beta 1 (TGF-beta 1) and thromboxane receptors were coordinately upregulated during differentiation but differentially regulated during proliferation. RNA fingerprinting revealed multiple transcripts specific to either proliferating or differentiated cells. Three of these were identified by homology to known DNA sequence: CDw44 adhesion molecule (upregulated during differentiation), glutathione sulfhydryl peroxidase (downregulated during differentiation), and plectin cytoskeletal protein (upregulated during differentiation). Thus, although megakaryoblast proliferation and megakaryocyte differentiation both involve DNA and protein synthesis, each growth response is characterized by a distinct pattern of gene expression. PMID- 8203488 TI - Shifts in type I fiber proportion in rat hindlimb muscle are accompanied by changes in HSP72 content. AB - Heat-shock protein 72 (HSP72), the inducible isoform of the HSP70 family, is constitutively expressed in rat hindlimb muscles in proportion to the content of type I muscle fibers. To determine whether this relationship was maintained after fiber transformation, male Sprague-Dawley rats were treated with 3,5,3'-triiodo DL-thyronine (T3) for 40 days or underwent surgical removal of the left gastrocnemius muscle, after which the left plantaris muscle was allowed to hypertrophy for 30 days. Hypertrophied plantaris muscles exhibited an increased number of type I fibers, type I myosin heavy-chain (MHC) protein, and HSP72 content compared with contralateral muscles. Soleus muscles from rats administered T3 exhibited an increased number of type II fibers, citrate synthase activity, and decreased HSP72 content compared with soleus muscles from controls. These results indicate that the relationship between HSP72 content and type I muscle fiber-MHC composition is maintained when muscles undergo fiber transformation and substantiate that HSP72 content in rat skeletal muscle is not directly linked to a muscle's oxidative capacity. PMID- 8203489 TI - Interactions between retinoic acid and 1,25(OH)2D in mouse immortalized osteoblastic C1 cells. AB - The interactions between 1,25-dihydroxyvitamin D3 [1,25(OH)2D] and retinoic acid (RA) on alkaline phosphatase (ALP) activity and vitamin D receptors (VDR) were determined in the SV40 immortalized osteoblastic cell line C1. Biochemical and cytochemical analysis showed that ALP activity increased with C1 cell density and that 1,25(OH)2D inhibited ALP activity at high density, whereas RA increased ALP activity at low density. The interactions of the two hormones were also cell density dependent, with a predominant stimulatory effect of RA at low density and a predominant inhibitory effect of 1,25(OH)2D at high density. In contrast, the two hormones inhibited C1 cell proliferation independently of cell density. Scatchard analysis and immunocytochemical staining showed that nuclear VDR levels increased with cell density and that RA, 1,25(OH)2D, and their combination upregulated VDR levels mainly at high cell density. Although RA increased VDR levels, RA did not potentiate the effect of 1,25(OH)2D on ALP activity. The results indicate that the effects and interactions of 1,25(OH)2D and RA on ALP activity in osteoblastic C1 cells depend on the state of phenotypic maturation. PMID- 8203490 TI - Responses of beta-adrenoceptor in rat soleus to phosphorus compound levels and/or unloading. AB - Responses of beta-adrenoceptor (beta-AR) in rat soleus to gravitational unloading and/or changes in the levels of phosphorus compounds by feeding either creatine or its analogue beta-guanidinopropionic acid (beta-GPA) were studied. A decrease in the density of beta-AR (about -35%) was induced by 10 days of hindlimb suspension, but the affinity of the receptor was unaffected. Suspension unloading tended to increase the levels of adenosine triphosphate and phosphocreatine and decrease inorganic phosphate. Even without unloading, the beta-AR density decreased after an oral creatine supplementation (about -20%), which also tended to elevate the high-energy phosphate levels in muscle. However, an elevation of beta-AR density was induced (about +36%) after chronic depletion of high-energy phosphates by feeding beta-GPA (about +125%). Data suggest that the density of beta-AR in muscle is elevated if the high-energy phosphate contents are chronically decreased and vice versa. However, it may not be directly related to the degree of muscle contractile activity. PMID- 8203492 TI - Neuropeptide Y stimulates hypertrophy of adult ventricular cardiomyocytes. AB - It was investigated whether neuropeptide Y (NPY) could exert a trophic effect on ventricular myocytes isolated from the adult rat heart. Two different culture models were used: day 1 and 7 cultures of cardiomyocytes. In day 1 and 7 cultures, NPY caused an increase in cellular protein mass. In day 1 cultures, NPY (10 nM) increased the protein-to-DNA ratio within 24 h by 10.1 +/- 2.8% (P < 0.01), but did not stimulate the incorporation of [14C]phenylalanine into cell proteins. The degradation of proteins was retarded in presence of NPY, revealed by pulse-chase experiments. In day 7 cultures, NPY (10 nM) increased the protein to-DNA ratio within 24 h by 33.9 +/- 5.0% (P < 0.01), increased the RNA-to-DNA ratio by 19.2 +/- 6.4%, and stimulated the incorporation of [14C]phenylalanine by 45.5 +/- 4.5% (P < 0.01). As in day 1 cultures, protein degradation was retarded. The specific activities of cytosolic creatine kinase and lactate dehydrogenase were increased in presence of NPY. This study demonstrates for the first time that NPY is a trophic factor for cardiomyocytes. NPY can cause an increase in cellular mass of protein, i.e., hypertrophy, by two mechanisms: 1) reduction of degradation of protein, found in day 1 and 7 cultures, and 2) stimulation of protein synthesis, observed only in day 7 cultures. The responsiveness of protein synthesis to NPY stimulation is induced during prolonged incubation in culture. PMID- 8203491 TI - Development of a H(+)-selective conductance during granulocytic differentiation of HL-60 cells. AB - The NADPH oxidase is one of the main microbicidal systems of granulocytes. Stimulation of the oxidase during infection leads to a burst of metabolic acid generation. Potentially deleterious cytosolic acidification is prevented by the simultaneous activation of homeostatic H+ extrusion mechanisms, including a recently described H+ conductance. Studies in granulocytes from chronic granulomatous disease patients have suggested a relationship between the oxidase and the H+ conductive pathway. In this report we compared the expression of the H+ conductance and the NADPH oxidase during granulocytic differentiation of dimethyl sulfoxide-induced HL-60 cells. Patch-clamp determinations demonstrated that the H(+)-selective current detectable in differentiated HL-60 cells is virtually absent in uninduced cells. The H+ conductance was also estimated fluorimetrically, measuring changes in the cytosolic pH of suspended cells. Imposition of an inward protonmotive force failed to induce significant cytosolic acidification. In contrast, a sizable conductive H+ extrusion was detected in acid-loaded differentiated cells, consistent with the rectifying properties of the current measured electrophysiologically. By the spectroscopic method, the H+ conductance was not detectable in uninduced cells, developing gradually during granulocytic differentiation. Development of the conductive pathway was found to parallel the biochemical and functional appearance of the NADPH oxidase. These findings suggest that the H+ extrusion mechanisms required for the maintenance of the intracellular pH during granulocyte activation develop pari passu with the acid generating systems and suggest a functional and possibly structural association between the H+ conductance and the NADPH oxidase. PMID- 8203493 TI - Aldosterone induces early activation and late accumulation of Na-K-ATPase at surface of A6 cells. AB - In A6 cells cultured on filters, aldosterone (10(-6) M) induces an early increase in the initial rate of ouabain binding to intact monolayers (in K-free buffer) that parallels an early increase in Na transport. This effect is independent of apical Na influx and precedes an increase in the synthesis of Na-K adenosinetriphosphatase (ATPase) subunits. In the present study we observed in addition a late aldosterone-induced increase in the rate of ouabain binding (2.5 times from 3 to 120 h aldosterone). The role of Na-K-ATPase accumulation and/or translocation to the cell surface was tested by Western blotting, saturation ouabain binding, and cell-surface labeling using sulfosuccinimidobiotin or enzyme mediated radioiodination. Only cell-surface beta 1-subunit was detected by blotting with streptavidin or autoradiography, because the alpha 1-subunit was not efficiently labeled. Three hours after hormone addition, none of the three parameters had increased significantly, whereas after 20 and 120 h similar increases (approximately 1.6 and 2.3 times, respectively) were detected by all three methods. In addition, it was shown that increasing intracellular Na with amphotericin B or a K-free preincubation also stimulated the rate of ouabain binding without increasing the surface labeling of beta 1-subunits. Taken together, these results suggest that a short aldosterone treatment or an increase in intracellular Na leads to an increase in the rate of ouabain binding that is due to an in situ activation of cell-surface Na-K-ATPase molecules. In contrast, the late increase in the rate of ouabain binding parallels an increase in the number of pumps. PMID- 8203494 TI - Modulation of Ca2+ transients by photorelease of caged nucleotides in frog skeletal muscle fibers. AB - Action potentials and intracellular Ca2+ transients were monitored in current clamped segments of frog skeletal muscle fibers using the triple vaseline-gap technique. Calcium signals were measured with the fluorescent indicator rhod 2. Action potentials produced a transient increase in intracellular Ca2+ that was estimated, by deconvolution of the fluorescence signals, to range between 3 and 12 microM. The comparative effects of flash photolysis of caged adenosine 3',5' cyclic monophosphate (cAMP) and caged ATP on action potentials and Ca signals in muscle were investigated. The photorelease of both nucleotides produced a reduction in the amplitude of the afterpotential that follows the spike. Photorelease of cAMP and ATP prolonged the rate of decay of the Ca signals. No changes in either the rate of rise or in the latent period between stimulation and onset of the Ca signal were observed. Release of cAMP reduced the amplitude of Ca signals, whereas release of ATP had the opposite effect. Our results show that cAMP and ATP, released above their endogenous levels, modulate intracellular Ca2+ release. The cAMP modulation is more significant and may be of physiological importance. PMID- 8203495 TI - Developmental cell-specific regulation of Na(+)-K(+)-ATPase alpha 1-, alpha 2-, and alpha 3-isoform gene expression. AB - Na(+)-K(+)-activated adenosine triphosphatase (Na(+)-K(+)-ATPase) is the integral membrane protein that maintains the Na(+)-K(+) electrochemical gradient across the plasma membrane. Because of the importance of the Na(+)-K(+) electrochemical gradient to fundamental and specialized cell functions, we investigated the cell specific modulation of Na(+)-K(+)-ATPase alpha-subunit isoform (alpha 1, alpha 2, and alpha 3) gene expression in different stages of postimplantation mouse embryos and neonatal rat tissues by in situ hybridization with use of isoform specific rat-derived antisense RNA probes. At early organogenesis (9.5-10.5 days postcoitus), we demonstrated generalized coexpression of alpha 1- and alpha 2 isoforms throughout the mouse embryo with greater levels in the developing but already functional heart, in contrast to the distinct spatially restricted alpha 3-isoform gene expression in the early developing neural tube. At midorganogenesis (15.5-16.5 days postcoitus), differential spatial variation in alpha 1-, alpha 2-, and alpha 3-isoform gene expression was already evident in all organs. Interestingly, region-specific expression patterns within single cell types were noted throughout development and were exemplified by 1) alpha 3 isoform gene expression in marginal cells of the 10.5-day-postcoitus developing neural tube; 2) alpha 1-, alpha 2-, and alpha 3-isoform gene expression in cerebellar granular cells of the 4-day-old rat brain; and 3) alpha 1- and alpha 3 isoform gene expression in 4-day-old rat ventricular cardiomyocytes. These isoform-specific changes in cellular and regional Na(+)-K(+)-ATPase alpha-isoform gene expression may play an active role in development and specialized cell functions. PMID- 8203496 TI - NMR-sensitive fluorinated and fluorescent intracellular calcium ion indicators with high dissociation constants. AB - A new series of high-dissociation constant (KD) Ca2+ indicators has been developed to reduce perturbations due to buffering of transients, to carry out measurements in cells and organelles with high basal Ca2+ concentrations, and to measure cytosolic Ca2+ levels in the presence of perturbations that may significantly increase these levels. A tetrafluorinated derivative of the chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, 1,2-bis(2 amino-5,6-difluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (TF-BAPTA), has a KD of 65 microM and exhibits two fluorine nuclear magnetic resonances, one of which is insensitive to Ca2+ chelation and the second of which shifts by approximately 10 ppm upon Ca2+ binding. TF-BAPTA has pK values of approximately 5.0 and Mg2+ dissociation constants > 50 mM. At a field of 8.5 T, the Ca(2+)-sensitive resonance is in fast-intermediate exchange. Correction factors for the effects of intermediate exchange and for the effect of protonation (pK approximately 5.0) and Mg2+ complexation are discussed. An analogous approach has been used to synthesize 2-[2-(5-carboxyoxazole)]-5-[2-(2-bis(carboxymethyl) amino-5,6 difluorophenoxy)]ethoxy-6-bis(carboxymethyl)aminobenz ofuran (fura F), a structural analogue of fura 2, which exhibits fluorescence characteristics similar to those of fura 2, but has a KD of 20 microM. PMID- 8203497 TI - Measurement of cytosolic free calcium in perfused rat heart using TF-BAPTA. AB - The feasibility and usefulness of loading 1,2-bis(2-amino-5,6 difluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (TF-BAPTA), a new high dissociation constant (KD) (65 microM) Ca2+ indicator, into perfused rat heart is demonstrated. TF-BAPTA-loaded perfused rat heart showed less than a 10% reduction in left ventricular developed pressure. In addition, loading perfused rat heart with TF-BAPTA had no effect on cell high-energy phosphates measured by 31P nuclear magnetic resonance (NMR). Cytosolic free Ca2+ (Ca2+i) can be monitored in TF-BAPTA-loaded perfused rat heart using 19F-NMR. TF-BAPTA has a Ca(2+) insensitive resonance (6F) and a Ca(2+)-sensitive fluorine (5F) that responds to changes in Ca2+ binding with fast exchange kinetics at magnetic fields < or = 8.5 T. Thus the shift difference between the 5F and 6F resonances is a measure of Ca2+i. Given the high KD and the slight differences in intra- vs. extracellular fluorine shifts, TF-BAPTA is not well suited for measuring basal Ca2+i, but it is useful for measuring increases in Ca2+i above this level. For studies in which intracellular pH changes are significant, e.g., during ischemia, pH-dependent corrections must be made to obtain an accurate Ca2+i value. Given its fast exchange kinetics, TF-BAPTA is also useful for measurement of free Ca2+ in different compartments or cells with different Ca2+i. We show that the rise in Ca2+i is not uniform during prolonged global ischemia (60 min); several different Ca2+i values are present. Thus TF-BAPTA is a useful new indicator for measuring elevations in Ca2+i or compartmentation of Ca2+i.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203498 TI - Role of cell volume variations in Na(+)-K(+)-ATPase recruitment and/or activation in cortical collecting duct. AB - The aim of this study was to examine whether cell volume variations could play a role in the previously reported Na(+)-K(+)-ATPase pump recruitment and/or activation induced by an increase in intracellular Na concentration (Nai) in cortical collecting ducts (CCD). Isolated CCD from kidneys of aldosterone repleted mice were incubated in hyper-, hypo-, or isosmotic solutions with and without Na to modify Nai and cell volume independently. Nai, cell volume, and the number of basolateral pumps were measured using 22Na, image analysis, and specific [3H]ouabain binding, respectively. Ouabain-sensitive 86Rb uptake was also measured. In CCD with high Nai, pump recruitment and/or activation was observed only when an increase in tubular volume was associated with Na load. Pump recruitment and/or activation was also induced by cell swelling in the absence of Na load. Recruited and/or activated pumps display an affinity for ouabain and a specific activity (ouabain-sensitive Rb uptake per pump unit) similar to basal pumps. We conclude that 1) cell swelling is implied in the process of Nai-dependent pump recruitment and/or activation, 2) cell swelling can promote pump recruitment and/or activation independently of Na load, 3) basal and recruited and/or activated pumps probably correspond to the same Na(+)-K(+) ATPase isoform. PMID- 8203499 TI - Interaction of cardiac Na-Ca exchanger and exchange inhibitory peptide with membrane phospholipids. AB - We tested the hypothesis that the exchange inhibitory peptide (XIP) domain in the cardiac Na-Ca exchanger is a regulatory site under the control of the membrane lipid environment. We found that 125I-XIP bound to liposomes composed of phosphatidylcholine (PC) and phosphatidylserine (PS) with peak binding at 1:1 PC/PS. No binding was observed in PC liposomes. XIP and pentalysine-inhibitable bovine sarcolemmal (SL) Na-Ca exchange activity was observed in reconstituted proteoliposomes composed of 1:1 PC/PS. Proteolysis of SL membranes resulted in a twofold stimulation of Na-Ca exchange activity, but the half-maximal inhibitory concentration (IC50) for XIP (3 microM) was not significantly changed, suggesting that the XIP binding site remained intact. In contrast, the IC50 for pentalysine was decreased from 500 to 150 microM in proteolyzed membranes. These data are consistent with a model of Na-Ca exchange regulation in which the endogenous XIP domain interacts either with another region of the exchange protein to induce an inactive conformational state or with membrane lipid to produce an active conformation. PMID- 8203500 TI - pH-dependent inhibitory effects of Ca2+, Mg2+, and K+ on Ca2+ efflux mediated by sarcoplasmic reticulum ATPase. AB - The effect of pH on the rate of Ca2+ efflux mediated by the Ca2+ adenosinetriphosphatase (ATPase) was measured. The cations Ca2+, Mg2+, and K+ decrease the rate of Ca2+ efflux at pH 7.5 but not at pH 6.0. The effect of pH on the affinity to Ca2+ during Ca2+ efflux was found to be similar to the pH dependence of the high-affinity Ca2+ binding sites of the ATPase. The inhibitory activity of cations was significantly increased by a rise in pH, whereas acidification amplified the magnitude of an efflux component insensitive to cations. Acidification of the assay medium allows efflux of Ca2+ through the Ca2+ pump, even in the presence of high concentrations of monovalent and divalent cations. The efflux rate was severalfold increased by addition of the hydrophobic drugs trifluoperazine, dibucaine, and imipramine. At neutral pH, the Ca2+ efflux induced by trifluoperazine was antagonized by the cations Ca2+, Mg2+, and K+ and by thapsigargin, a highly specific inhibitor of the Ca2+ pump. In contrast to that observed at neutral pH, the cations did not antagonize the effect of trifluoperazine on Ca2+ efflux at acid pH. It is concluded that H+ produces functional alterations in ATPase domains involved in Ca2+ efflux. PMID- 8203501 TI - Effects of vanadate on MgATP stimulation of Na-Ca exchange support kinase phosphatase modulation in squid axons. AB - We have proposed that in squid axons MgATP stimulation of Na-Ca exchange involves a phosphorylation-dephosphorylation process catalyzed by a kinase-phosphatase system. In the present work, we used vanadate as a tool to gather further evidence about the mechanism of metabolic control of the Na-Ca exchanger in internally dialyzed and voltage-clamped squid axons. Vanadate, at concentrations up to 100 microM, stimulated extracellular Na (Nao)-dependent Ca efflux only in the presence of MgATP but failed to do so when the axons were dialyzed with the nonhydrolyzable ATP analogue beta, gamma-methyleneadenosine 5'-triphosphate or with CrATP, a MgATP analogue that completely abolishes MgATP stimulation of the Na-Ca exchange. In axons fully activated by Mg-adenosine 5'-O-(3 thiotriphosphate), vanadate had no effect on Na-Ca exchange. The dose-response curve for vanadate stimulation followed Michaelian kinetics with a Km of 5.6 +/- 0.4 microM and a maximum velocity of 216 +/- 10 fmol.cm-2.s-1 (intracellular Ca concentration = 0.8 microM). This coincides with the high affinity of vanadate in inhibiting the in vitro phosphatase activity of an alkaline phosphatase extracted from rat liver. In addition, vanadate increased fivefold the apparent affinity for MgATP (Km from 220 +/- 14 to 40 +/- 4 microM). Concentrations of vanadate in the millimolar range inhibited the MgATP-stimulated Na-Ca exchange (apparent Ki of 5.7 +/- 0.3 mM) and the in vitro phosphorylation by the catalytic subunit of a adenosine 3',5'-cyclic monophosphate protein kinase (apparent Ki 2.64 +/- 0.04 mM). We conclude that MgATP stimulation of Na-Ca exchange is proportional to the levels of phosphorylation that result from the balance of the activity of a kinase and a phosphatase activity. PMID- 8203502 TI - Prostaglandin E2 synthesis after oxidant stress is dependent on cell glutathione content. AB - The role of glutathione in protecting prostaglandin (PG) generation after exposure of fibroblasts to oxidant stress was investigated. Exposure of 3T3 fibroblasts to H2O2, followed by washing and then 20 microM arachidonic acid, caused a dose-dependent decrease in PG synthesis as assessed by radioimmunoassay. PGE2 production decreased from 3.7 +/- 1.1 to 0.15 +/- 0.04 pmol/microgram protein, and prostacyclin (PGI2) formation decreased from 0.56 +/- 0.03 to 0.06 +/- 0.03 pmol/microgram protein after exposure to 200 microM H2O2. Decreasing intracellular glutathione with 50 micrograms/ml 1,3-bis(chloroethyl)-1 nitrosourea (BCNU) enhanced the H2O2-induced decrease in PGE2 synthesis. Another glutathione-depleting agent, 1-chloro-2,4-dinitrobenzene (CDNB), also potentiated the H2O2-induced decrease in PGE2 formation. However, although PGI2 production was decreased by H2O2, neither BCNU nor CDNB potentiated this decrease. Without oxidant stress, extreme glutathione depletion decreased PGE2 synthesis and caused PGI2 synthesis to exceed PGE2. In summary, oxidant stress decreases both PGE2 and PGI2 formation. However, the primary effect of decreasing cell glutathione during oxidant stress is a reduction in PGE2 formation, not PGI2. This implies that the predominant effect of glutathione depletion during oxidant stress is on the PGE2 isomerase(s) and not PGH synthase or PGI2 synthase. PMID- 8203503 TI - ESR spectral transition by arteriovenous cycle in nitric oxide hemoglobin of cytokine-treated rats. AB - Nitric oxide (NO) generation was induced in rats by Escherichia coli lipopolysaccharide (LPS) as detected by electron spin resonance (ESR) signals of NO hemoglobin (HbNO). However, there were inconsistencies in ESR spectral shape among them. We have therefore carried out a systematic study to clarify the in vivo spectral changes. First, the spectra of the alpha-NO heme species had the distinct three-line hyperfine structure in venous blood but not in arterial blood in all rats treated with tumor necrosis factor, interleukin-1, and/or LPS, and methemoglobin was not detected at the g = 6 (high-spin methemoglobin) region. Second, when the treated rats died, the three-line hyperfine structure was very distinct even in arterial blood. Third, even if HbNO was formed by injection of nitrite to rats, the three-line hyperfine structure of HbNO in venous blood was more marked than that in arterial blood, independent of the appearance of the methemoglobin signal. Fourth, an ex vivo study using whole blood demonstrated that the three-line hyperfine structure intensified lineally when O2 saturation of hemoglobin decreased but disappeared on reoxygenation of hemoglobin. These results directly demonstrate in vivo quaternary structural transition of the hemoglobin tetramer from the high-affinity state in the arterial cycle to the low affinity state in the venous cycle. The transition makes the diverse ESR spectra of HbNO in vivo. PMID- 8203504 TI - Bradykinin and angiotensin II: activation of protein kinase C in arterial smooth muscle. AB - The effects of bradykinin (BK) and angiotensin II (ANG II) were compared in cultured rat mesenteric arterial smooth muscle cells. BK and ANG II activated a phosphoinositide-specific phospholipase C, leading to the rapid release of [3H]inositol phosphates, an increase in intracellular calcium, and formation of sn-1,2-diacylglycerol (DAG). DAG formation was biphasic with a transient peak at 5 s followed by a sustained increase from 60 to 600 s. The BK-mediated increases in inositol triphosphate and DAG were dose dependent with half-maximal increases at concentrations of 5 and 2 nM, respectively. Both hormones were found to activate protein kinase C (PKC) as assessed by phosphorylation of the 68- to 72 kDa intracellular PKC substrate myristoylated alanine-rich C kinase substrate. However, despite similar phosphorylation of this substrate, only ANG II produced a significant increase in membrane-bound PKC activity. The mechanism accounting for the inability of BK to increase membrane-bound PKC activity is unclear. Our studies excluded differential translocation of PKC to the nuclear membrane, production of an inhibitor of membrane-bound PKC activity, and expression of BK and ANG II receptors on different cells as the mechanism. Vascular smooth muscle cells were found to express at least four different PKC isozymes: alpha, delta, zeta, and a faint band for epsilon. All of the isozymes except zeta-PKC were translocated by treatment with the phorbol ester 4 beta-phorbol 12-myristate 13 acetate. However, neither ANG II nor BK produced significant translocation of any measured isozyme; therefore, we could not exclude the possibility that ANG II and BK activate different isozymes of PKC. Both hormones were found to have a similar small and inconsistent effect in stimulating [3H]thymidine incorporation. These observations demonstrate that BK and ANG II have similar biochemical effects on vascular smooth muscle cells and imply that, in selected vessels, the vasodilatory effects of BK mediated by the endothelium may be partially counterbalanced by a vasoconstrictor effect on the underlying vascular smooth muscle cells. PMID- 8203505 TI - Modulation by L-type Ca2+ channels and apamin-sensitive K+ channels of muscarinic responses in cat chromaffin cells. AB - In the perfused cat adrenal gland stimulated with the muscarinic agonist methacholine chloride (100 microM for 3 min), two components were detected in the catecholamine secretory response: 1) an early phasic component that peaked at 300 ng/5 s catecholamine release and 2) a tonic component whose peak was transient and declined to a plateau of about 140 ng/5 s. Apamin (0.1 microM) increased the phasic component to 1,200 ng/5 s and the tonic component to approximately 350 ng/5 s. In single fura 2-loaded cat adrenal chromaffin cells, the cytosolic Ca2+ concentration ([Ca2+]i) also followed a biphasic pattern after stimulation with methacholine. Depletion of extracellular Ca2+ reduced the phasic [Ca2+]i peak by > 50% and the phasic secretory peak by approximately 90%; both the tonic components of [Ca2+]i and secretion were abolished. Depletion of intracellular Ca2+ pools decreased the phasic and tonic components of [Ca2+]i and secretion with respect to control values; however, the phasic components diminished more than the tonic components of [Ca2+]i and secretion. Although 3 microM furnidipine (a dihydropyridine L-type Ca2+ channel blocker) inhibited the phasic component of [Ca2+]i and secretion, its effects were more pronounced on the tonic component. omega-Conotoxin GVIA (1 microM, an N-type Ca2+ channel blocker) did not affect the [Ca2+]i or the methacholine secretory responses. The secretion peak seems to depend on both extracellular free Ca2+ (Cao2+) entry through L-type Ca2+ channels as well as on the mobilization of Ca2+ from intracellular stores; the plateau depends only on Cao2+ entry through L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203506 TI - Na-K-Cl cotransport in nystatin-treated tracheal cells: regulation by isoproterenol, apical UTP, and [Cl]i. AB - Chloride secretion in mammalian airway epithelia is stimulated by beta-adrenergic agonists via an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent mechanism and by apical triphosphate nucleotides (ATP, UTP) via a cAMP-independent mechanism. Both types of secretagogues are known to stimulate apical Cl channels in airway cells; however, to maintain a stimulated rate of secretion, basolateral Cl influx via Na-K-Cl cotransport must be upregulated in parallel with apical Cl efflux. To examine the regulation of basolateral cotransport activity and its relationship to apical Cl efflux, we examined Cl transport in confluent primary cultures of dog tracheal epithelial cells treated with nystatin, an antibiotic that increases the permeability of plasma membranes to small monovalent ions, including Cl. By applying nystatin to the apical membrane of these cultures, apical Cl permeability could be increased to the point where transepithelial Cl transport is limited by transport across the basolateral membrane, which reflects primarily the activity of the cotransporter. In cultures of tracheal cells not treated with nystatin, transepithelial (basolateral-to-apical) 36Cl flux was increased two- to threefold by exposure to isoproterenol (5 microM, basolateral) or apical UTP (10 microM). Apical application of nystatin (400 units/ml) increased the basal level of transepithelial 36Cl flux approximately 1.5-fold and eliminated UTP stimulation of this flux, although an approximately twofold stimulation by isoproterenol persisted. Nystatin treatment also abolished UTP stimulation of saturable, basolateral [3H]bumetanide binding, a measure of functioning Na-K-Cl cotransporters in these cells; isoproterenol stimulation of binding was only mildly inhibited by nystatin treatment. Lowering intracellular Cl concentration ([Cl]i) by incubating cultures with apical media containing nystatin and reduced [Cl] (NO3 replacement) increased both basolateral-to-apical 36Cl flux and [3H]bumetanide binding in the absence of secretagogues or cell shrinkage. The results support our previous suggestion, based entirely on [3H]bumetanide binding [M. Haas, D. G. McBrayer, and J. R. Yankaskas. Am. J. Physiol. 264 (Cell. Physiol. 32): C189-C200, 1993], that UTP stimulation of basolateral Na-K-Cl cotransport in airway epithelial cells is entirely secondary to, and requires, an increase in apical Cl efflux, and further suggest that a decrease in [Cl]i may be a signal for cotransport activation in response to UTP. In addition, a cAMP-dependent cascade initiated by isoproterenol appears to directly stimulate the cotransporter. PMID- 8203507 TI - Anabolic effect of IGF-I coinfused with total parenteral nutrition in dexamethasone-treated rats. AB - We determined the anabolic effects of recombinant human insulin-like growth factor I (rhIGF-I, 800 micrograms/day) coinfused with total parenteral nutrition (TPN) in male Sprague-Dawley rats (230-250 g), with and without dexamethasone (Dex, 70 micrograms/day)-induced catabolism for 6 days. Dex without IGF-I increased serum insulin concentrations 300% and glucose concentrations 20%; IGF-I plus Dex significantly reduced serum insulin and glucose concentrations to TPN control levels. Animals given Dex without IGF-I lost 30 +/- 3 g; IGF-I plus Dex reduced the weight loss to 9 +/- 3 g, P < 0.001. IGF-I without Dex resulted in a weight gain of 14 +/- 2 g compared with a gain of 4 +/- 1 g in TPN controls, P < 0.01. Determination of nitrogen balance and body composition confirmed that changes in body weight were due to corresponding changes in nitrogen excretion and total body protein content. IGF-I significantly reduced TPN-induced intestinal atrophy, resulting in a 30% increase in weight of the small intestine plus colon compared with TPN without IGF-I. These results indicate that coinfusion of rhIGF-I with TPN counteracts Dex-induced insulin resistance and has a significant net anabolic effect when given with or without Dex in rats. PMID- 8203508 TI - In vivo measurement of fatty acids and cholesterol synthesis using D2O and mass isotopomer analysis. AB - The synthesis of palmitate, stearate, and cholesterol in liver and nervous tissues (brain, cord, and nerve) of Sprague-Dawley rats was determined using deuterated water (D2O) and mass isotopomer analysis. Rats were given 4% deuterium in their drinking water after each receiving an intraperitoneal priming dose. Animals were killed at 1, 2, 4, and 8 wk for deuterium enrichment in body water and determination of mass isotopomer distribution in lipids from various tissues. In 1 wk, the enrichment in the body water reached a plateau of 2.6%, which is 65% of that in the drinking water. We observed the maximum incorporation number (N) in all lipids to be higher than those previously observed, being 22, 24, and 30 for liver palmitate, stearate, and cholesterol, respectively, and N may vary among tissues. Using a single exponential model, we found the half-time (t1/2) and the plateau levels of the newly synthesized lipids of the nervous tissues (t1/2 values ranging from 5 to 28 days) to be different from those of the liver (t1/2 values < or = 4 days) in this relatively long-term study. Mass isotopomer distribution analysis and D2O can be used not only to quantitate the replacement rate of many lipids in various compartments but may also be used to elucidate the tissue-specific synthetic pathways from N. PMID- 8203509 TI - IGF-I mediates the stimulatory effect of high calcium concentration on osteoblastic cell proliferation. AB - Since our recent study revealed that an increase in extracellular calcium ([Ca2+]e) but not magnesium enormously stimulated DNA synthesis in osteoblastic MC3T3-E1 cells at the minimal and maximal effective concentration of 3 and 5 mM, respectively, the present study was performed to clarify how an increase in [Ca2+]e caused a stimulation of DNA synthesis of these cells. Neither calcium channel blockers (verapamil, diltiazem, and nifedipine) and dantrolene, an inhibitor of Ca release from intracellular Ca pool, nor indomethacin, an inhibitor of prostaglandin synthesis, affected the high [Ca2+]e-induced increase in DNA synthesis. DNA synthesis first increased after a 12-h exposure to 5 mM [Ca2+]e, and cycloheximide eliminated the stimulatory effect of high [Ca2+]e on DNA synthesis, suggesting that this stimulatory effect of high [Ca2+]e was dependent on new protein synthesis. There is recent evidence that MC3T3-E1 cells constitutively produce and secrete insulin-like growth factor I (IGF-I) and possess IGF-I receptors. IGF-I antiserum (1:10,000 to 1:100) blocked the high [Ca2+]e-induced increase in DNA synthesis in a concentration-dependent manner. A neutralizing abolished DNA synthesis stimulated by high [Ca2+]e, indicating that IGF-I mediated the high [Ca2+]e-induced effect. Furthermore, high [Ca2+]e significantly increased the secretion of immunoreactive IGF-I into the medium as well as the expression of IGF-I mRNA. Present findings indicate that an increase in [Ca2+]e stimulated DNA synthesis of osteoblasts through the mechanism of an increase in the production and secretion of IGF-I. PMID- 8203510 TI - Arterial alpha-adrenergic responsiveness is decreased and SNS activity is increased in older humans. AB - We tested the hypotheses that 1) there is an age-associated decrease in arterial alpha-adrenergic responsiveness and 2) there is upregulation of this response during suppression of sympathetic nervous system (SNS) activity. We measured forearm blood flow (FABF) by plethysmography during brachial artery infusions of the alpha-adrenergic agonist norepinephrine (NE) and the nonadrenergic agonist angiotensin II (ANG II) in 15 young and 14 older healthy human subjects. Among the old (O) relative to the young (Y) we identified greater plasma NE levels (Y: 1.29 +/- 0.07 nM vs. O: 2.14 +/- 0.17 nM; P = 0.0001); a decrease in NE-mediated reduction in FABF [analysis of variance (ANOVA) P = 0.04]; and, in contrast, no difference in ANG II-mediated reduction in FABF (ANOVA P = 0.43). In the nine older subjects studied during guanadrel (G) to suppress SNS activity, we identified decreased plasma NE levels [placebo (P): 2.11 +/- 0.24 nM vs. G: 1.09 +/- 0.09 nM; P = 0.002], increased NE-mediated FABF response (ANOVA P = 0.01), and no difference in FABF response to ANG II (ANOVA: P = 0.69) compared with P. We conclude that there is appropriate desensitization of arterial alpha adrenergic responsiveness among the older relative to the young subjects that is specific for the alpha-adrenergic system. Among the older subjects there is homologous upregulation of this response when SNS activity is suppressed. PMID- 8203511 TI - Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. AB - Biopsy samples were obtained from the vastus lateralis muscle of eight subjects after 0, 20, 60, and 120 s of recovery from intense electrically evoked isometric contraction. Later (10 days), the same procedures were performed using the other leg, but subjects ingested 20 g creatine (Cr)/day for the preceding 5 days. Muscle ATP, phosphocreatine (PCr), free Cr, and lactate concentrations were measured, and total Cr was calculated as the sum of PCr and free Cr concentrations. In five of the eight subjects, Cr ingestion substantially increased muscle total Cr concentration (mean 29 +/- 3 mmol/kg dry matter, 25 +/- 3%; range 19-35 mmol/kg dry matter, 15-32%) and PCr resynthesis during recovery (mean 19 +/- 4 mmol/kg dry matter, 35 +/- 6%; range 11-28 mmol/kg dry matter, 23 53%). In the remaining three subjects, Cr ingestion had little effect on muscle total Cr concentration, producing increases of 8-9 mmol/kg dry matter (5-7%), and did not increase PCr resynthesis. The data suggest that a dietary-induced increase in muscle total Cr concentration can increase PCr resynthesis during the 2nd min of recovery from intense contraction. PMID- 8203512 TI - Effects of sialoadenectomy and exogenous EGF on molar drift and orthodontic tooth movement in rats. AB - Effects on bone remodeling have been attributed to epidermal growth factor (EGF). Sialoadenectomy (SX) removes the major source of EGF in rodents and decreases both salivary and serum EGF levels. EGF effects on rat alveolar bone remodeling manifested by molar drift (MD) and orthodontic tooth movement (OTM) were examined using the following two approaches: 1) EGF depletion by SX and replacement by orally administered EGF (50 micrograms.animal-1.day-1); 2) sham rats supplemented with matching amounts of EGF. MD and OTM were measured using cephalometric radiographs; bone formation was measured histomorphometrically using tetracycline labeling. Normal MD was not detected after SX, and alveolar bone formation was significantly reduced both around the tooth and in nondental sites. Replacement EGF given to SX rats and supplemental EGF administered to sham rats changed the direction and enhanced the rate of MD. A mesially directed orthodontic force applied to the molars of SX animals increased bone formation on the distal aspect of the tooth roots. Supplemental EGF did not significantly affect OTM. EGF affects alveolar bone remodeling, as manifested clinically by alterations in normal maxillary MD. PMID- 8203513 TI - Continuous on-line hydrogen ion monitoring to study flow dynamics of perifusion systems and cellular metabolism. AB - Time-dependent concentration profiles of input signals and feedback of metabolic products can strongly influence cellular responsiveness. To study these parameters, we developed a perifusion system that can deliver biological signals to cells with minimal dispersion, monitor real time responses, and remove waste products continuously. By monitoring pH with miniature hydrogen ion-selective electrodes at intervals of 1 s, effects of dispersion, flow rate, pumping system, and changes in cellular metabolism were demonstrated. Dynamic responses of a human cell line to a series of 10-min pulses of the metabolic uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) were monitored. A rapid 1-min increase in acid release occurred on exposure to CCCP, followed by a decrease in acidification and then a gradual return to a baseline slightly more acidic than before administration of CCCP. These observations demonstrate that this perifusion system can reveal small changes in pH (+/- 0.0005 units) induced by metabolic perturbations and has the potential to reveal the dynamics of cellular responsiveness to a wide range of hormonal, metabolic, and other chemical signals. PMID- 8203514 TI - Regulation of metallothionein concentrations in rat brain: effect of glucocorticoids, zinc, copper, and endotoxin. AB - The effects of known inducers of liver metallothionein (MT) synthesis on MT concentrations in the rat brain have been determined using antibodies that are specific for MT I and II and do not cross-react with MT III. There were substantial differences in the MT concentrations in different areas of the brain. Dexamethasone increased MT levels after 24 h in the frontal cortex, cortex, medulla oblongata plus pons, midbrain, striatum, hippocampus, and cerebellum but not in the hypothalamus. Corticosterone produced similar results except in the hippocampus. Long-lasting adrenocorticotropic hormone increased MT concentrations after 12 h in midbrain and striatum but not in the liver. Adrenalectomy decreased MT concentrations after 6 days in the medulla oblongata plus pons, striatum, hippocampus, and hypothalamus but increased concentrations in the liver and kidneys; these effects were reversed by corticosterone. The role of glucocorticoids in the regulation of MT levels therefore differs between tissues and within specific areas of the brain. Injection of zinc or copper intracerebroventricularly and the use of a zinc-deficient diet increased and decreased MT levels, respectively, in some but not all brain areas. Endotoxin increased liver MT but not brain MT I levels after 8 h. PMID- 8203515 TI - T4 uptake into the perfused rat liver and liver T4 uptake in humans are inhibited by fructose. AB - Recently, we described a two-pool model for 3,5,3'-triiodothyronine uptake and metabolism in the isolated perfused rat liver. Here, we applied this model to investigate transmembrane thyroxine (T4) transport and its possible ATP dependence in vivo. These studies are performed in perfused rat livers during perfusion with or without fructose in the medium, as it has been shown that intracellular ATP is decreased after fructose loading. Furthermore, we studied serum T4 tracer disappearance curves in four human subjects before and after intravenous fructose loading. In the perfused rat liver, we found a decrease in liver ATP concentration and a decrease in medium T4 disappearance and T4 uptake in the liver pool after fructose. Furthermore, it was shown that, when corrected for differences in the medium free hormone concentration, only transport to the metabolizing liver pool was decreased after fructose perfusion, whereas uptake in the nonmetabolizing pool was unaffected. Disposal, corrected for differences in transport into the metabolizing pool, was also not affected after fructose. In the human studies, intravenous fructose administration induced a rise in serum lactic acid and uric acid, indicating a decrease in liver ATP. This was observed concomitant with a decrease in serum tracer T4 disappearance during the first 3 h after fructose administration. These results suggest ATP dependence of transport of iodothyronines into the liver in vivo and show that, in the rat liver and in humans, uptake of T4 may be regulated by intracellular energy stores; in this way the tissue uptake process may affect intracellular metabolism and bioavailability of thyroid hormone. PMID- 8203516 TI - Changes in serum triiodothyronine kinetics and hepatic type I 5'-deiodinase activity of cold-exposed swine. AB - Swine exposed to cold air have elevated serum values of total triiodothyronine (TT3) and free T3 (FT3). To characterize the mechanism of these increases, we measured in vivo kinetic parameters after a bolus intravenous injection of 125I labeled T3 by use of both multicompartmental (MC) and noncompartmental (NC) methods and in vitro hepatic type I iodothyronine 5'-deiodinase (5'D-I) activity. Ten ad libitum-fed 5-mo-old boars were divided into two groups, living for 25 days in either control (22 degrees C) or cold (4 degrees C) conditions. Cold exposed animals consumed 50% more calories than control animals but showed no difference in total body weight, percent body fat, or plasma volume. Thyroid gland weight was increased 86% (P < 0.004), as was serum total thyroxine (TT4) (48%), free T4 (FT4) (61%), TT3 (103%), and FT3 (107%), whereas serum thyrotropin (TSH) was not different in cold-exposed compared with control animals. The T3 plasma clearance rate was similar between groups when both MC and NC techniques were used. However, T3 plasma appearance rate (PAR) was elevated in cold-treated animals 110% over controls by MC (P < 0.001) and 83% by NC methods (P < 0.001). The animal total hormone pool of T3 was increased 76% (MC) and 53% (NC) compared with control (P < 0.01). The Michaelis constant of hepatic 5'D-I was not different between groups, but the maximum enzyme velocity increased (106%; P < 0.02). Therefore cold exposure for 25 days is associated with increased energy intake, thyroid size, T3 PAR, and hepatic 5'D-I activity with little change in serum TSH. PMID- 8203517 TI - Liver glycogen turnover in fed and fasted humans. AB - Whether liver glycogen synthesis and breakdown occur simultaneously during net glycogen synthesis was assessed in fed and fasted healthy humans. The peak intensity of the carbon-1 (C1) resonance of the glycosyl units of glycogen was monitored with 13C nuclear magnetic resonance spectroscopy during [1-13C]glucose infusion followed by unlabeled glucose infusion. The C1 peak intensity increased almost linearly during the [1-13C]glucose infusion, reflecting a near linear rate of glycogen synthesis. When switched to unlabeled glucose, the C1 peak intensity reached a plateau in the fasted subjects and declined in the fed subjects, reflecting active glycogenolysis during a time of net glycogen synthesis. We conclude that liver glycogen synthesis and degradation occur simultaneously in humans under conditions of net glycogen synthesis. The relative turnover rate was significantly higher in the fed (57 +/- 3%) than in the fasted state (31 +/- 8%; P < 0.01). The results indicate that glycogen may regulate its rate of breakdown and that liver glycogen turnover may be an important factor in limiting the accumulation of liver glycogen in humans. PMID- 8203518 TI - Canine liver releases neuropeptide Y during sympathetic nerve stimulation. AB - To determine whether the liver or gut releases neuropeptide Y (NPY) from their sympathetic nerves, we performed bilateral thoracic sympathetic nerve stimulation (BTSNS) in halothane-anesthetized dogs and calculated gut and liver NPY spillover. BTSNS markedly increased hepatic NPY spillover (delta = +32 +/- 8 ng/min) and arterial NPY concentration (delta = +220 +/- 56 pg/ml), despite no effect on gut NPY spillover (delta = +8 +/- 7 ng/min). To determine the liver's contribution to this increase of circulating NPY, hepatic nerves were selectively stimulated (HNS). Liver NPY spillover increased markedly (delta = +114 +/- 42 ng/min, P < 0.025) during HNS, causing a large increase of arterial NPY (delta = +586 +/- 237 pg/ml, P < 0.025). Using this ratio of liver spillover to arterial increments of NPY, we calculated that the liver makes a major contribution (70%) to circulating NPY levels during BTSNS. The predominant form of canine NPY coeluted with synthetic [Met17]NPY and the minor form of canine NPY coeluted with the oxidized form of [Met17]NPY on high-performance liquid chromatography. We therefore conclude that dog NPY is likely [Met17]NPY and that the liver, rather than the gut, is a major source of circulating NPY during sympathetic nerve stimulation and perhaps stress. PMID- 8203519 TI - Expression of the insulin-regulatable transporter GLUT-4 in muscle is influenced by neurogenic factors. AB - To investigate whether the expression of GLUT-4 is influenced by neurogenic factor(s) released from the nerve to the muscle, we measured GLUT-4 at different time points after sectioning the sciatic nerve at different locations in two groups of rats. Specifically, GLUT-4 was measured at 12, 24, and 48 h after severing the sciatic nerve. In one group of animals the muscles were left either with a short nerve stump attached to the muscle, or, in another group of animals, a long nerve stump remained attached to the muscle. In both groups of animals the contralateral limb served as a control. We examined GLUT-4 in the red (RG) and white gastrocnemius (WG), since the RG is highly responsive to denervation and the WG is quite resistant to denervation [L. A. Megeney, P.D. Neufer, G. L. Dohm, M. H. Tan, C. A. Blewtt, G. C. B. Elder, and A. Bonen. Am. J. Physiol. 264 (Endocrinol. Metab. 27): E583-E593, 1993]. In the long nerve stump WG no change in GLUT-4 was observed at 12, 24, or 48 h after denervation (P > 0.05). In the short nerve stump WG, changes were not evident at 12 and 24 h (P > 0.05), but by 48 h a significant decrement (-12.7 +/- 6.7%) was observed (P < 0.05). GLUT-4 changes were only evident 48 h after denervation (-19.8 +/- 4.5%; P < 0.05) in the long nerve stump RG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203520 TI - Plasma membrane clustering of system y+ (CAT-1) amino acid transporter as detected by immunohistochemistry. AB - Transport of cationic amino acids in fully differentiated mammalian cells is mediated primarily by system y1+ [cationic amino acid transporter (CAT)-1 gene product]. Antibodies, prepared against synthetic peptide sequences predicted to be extracellular loops of the CAT-1 transporter protein, detected the transporter on the surface of cultured cells. In human fibroblasts, porcine pulmonary artery endothelial cells, and cultured rat hepatoma cells, the CAT-1 transporter protein was clustered in an apparent random pattern throughout the plasma membrane. In contrast, labeling of the fibroblasts with antibodies against the epidermal growth factor receptor or the GLUT-1 glucose transporter demonstrated a uniform staining pattern covering the entire cell surface. The CAT-1 antibody labeling was specific, as demonstrated by peptide inhibition and the lack of staining by preimmune serum. Furthermore, hepatocytes did not exhibit specific antibody binding consistent with the lack of system y1+ activity. Disruption of the microtubule assembly resulted in a reversible loss of the CAT-1 transporter clusters and a more generalized labeling of the cell body. The data demonstrate the existence of microdomains within the plasma membrane that contain the CAT-1 transporter protein. PMID- 8203521 TI - On the calculation of glucose rate of disappearance in nonsteady state. PMID- 8203522 TI - pHi and HCO3- dependence of proton extrusion and Cl(-)-base exchange rates in isolated rabbit parietal cells. AB - In many cell types, the regulation of intracellular pH (pHi) is different in the presence vs. absence of HCO3-. We investigated the pHi and HCO3- dependence of proton extrusion and anion exchange rates in isolated rabbit parietal cells loaded with the pH-sensitive dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). In Cl(-)-depleted parietal cells, the dependence of maximal proton efflux rate on pHi showed a strong inverse correlation but was identical in the presence and absence of HCO3-. Amiloride and Na+ removal inhibited proton extrusion rates to a similar degree with or without HCO3-, whereas 4,4' diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) had no effect. This suggests that a Na(+)-H+ exchanger is the major acid extrusion ion transporter under these experimental conditions. In Cl(-)-containing cells, there was also some Na(+) independent, extracellular HCO(3-)- and intracellular Cl(-)-dependent, DIDS inhibitable pHi recovery from an acid load, most likely due to intracellular Cl( )-extracellular HCO3- exchange. Recovery from an alkaline load was primarily mediated by anion exchange, and the dependence of maximal anion exchange rates on pHi was very different in the absence and presence of HCO3-. In its absence, maximal anion exchange (Cl(-)-OH-) rates increased slowly over the tested pHi range from 6.4 to 7.8. In the presence of HCO3-, however, there was an S-shaped dependence of maximal flux rates on pHi, with a steep increase in flux rates between 6.8 and 7.5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203523 TI - Differential signal transduction pathways in cat lower esophageal sphincter tone and response to ACh. AB - Lower esophageal sphincter (LES) basal tone and contraction in response to maximally effective doses (Emax) of acetylcholine (ACh) may be mediated by different intracellular transduction pathways. In the basal state resting tone, inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] formation and levels of diacylglycerol (DAG) (C. Hillemeier, K. N. Bitar, and P. Biancani, unpublished data) are higher in LES circular muscle than in esophageal muscle, which does not maintain tone. In vitro resting tone and spontaneously elevated formation of Ins(1,4,5)P3 in LES circular muscle strips decrease in a dose-dependent manner in response to the phospholipase C antagonist 1-[6-([(17-beta)-3-methoxyestra-1,3, 5(10)-trien-17-yl]amino)hexyl]-1H-pyrrole-2,5-dione (U-73122). Basal Ins(1,4,5)P3 formation, however, is submaximal, since it can be increased by cholinergic stimulation. These data suggest that LES tone is associated with partial activation of phospholipase C. We therefore tested submaximal doses of Ins(1,4,5)P3 and DAG in permeabilized LES muscle cells and found that they act synergistically; their interaction depends on calcium release and is mediated through a protein kinase C (PKC)-dependent pathway. In contrast, we have previously shown that contraction induced by Emax of ACh is mediated through calmodulin-dependent mechanisms (14). To investigate these differences, we tested high and low doses of ACh. Contraction induced by high doses of ACh was inhibited by calmodulin but not by PKC antagonists, as previously reported, but low ACh doses were preferentially inhibited by PKC antagonists. Similarly, low Ins(1,4,5)P3 concentrations activated a PKC-dependent pathway, whereas contraction induced by Emax of Ins(1,4,5)P3 was calmodulin dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203525 TI - Inhibition of nitric oxide formation in vivo enhances superoxide release by the perfused liver. AB - Nitric oxide, a known scavenger of toxic oxygen-derived radicals, has been shown to have a protective effect against tissue injury in endotoxemia. Based on the hypothesis that under normal physiological conditions, a balance between superoxide and nitric oxide exists in vivo, this work examines hepatic superoxide release after nitric oxide formation is inhibited in vivo. Male Sprague-Dawley rats were treated intravenously with N omega-nitro-L-arginine methyl ester (L NAME; 50 mg/kg body wt), an inhibitor of nitric oxide synthase. One hour later, superoxide anion release by the perfused liver was determined. Results show that a significant amount of superoxide was released after L-NAME treatment. Likely sources of this radical are the Kupffer cells. Inhibition of nitric oxide formation in vivo did not enhance superoxide release by hepatocytes or sinusoidal endothelial cells. The effect of L-NAME treatment on superoxide release in endotoxemic rats was also examined 12 h after lipopolysaccharide treatment, when toxic oxygen-derived radical formation could not be detected. Inhibition of nitric oxide release in vivo in these rats enhanced the formation of superoxide anion. The interaction between nitric oxide and superoxide anion under normal conditions may represent an important protective mechanism of the host against free radical damage. PMID- 8203524 TI - Stimulation of rat parietal cell function by histamine and GLP-1-(7-36) amide is mediated by Gs alpha. AB - It was the aim of the present study to determine in rat parietal cells whether Gs alpha, the stimulatory subunit of adenylate cyclase, mediates adenosine 3',5' cyclic monophosphate (cAMP)-dependent parietal cell function in response to histamine and glucagon-like peptide 1 (GLP-1)-(7-36) amide. Cytoplasmic membrane from enriched (83 +/- 5%) rat parietal cells were incubated for 30 min with 30 microCi/ml [32P]NAD+ and 40 micrograms/ml preactivated cholera toxin (CT), a pharmacological tool for activation of Gs alpha. Subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography revealed [32P]ADP ribosylation of Gs alpha represented by three proteins with molecular masses ranging from 42 to 45 kDa. In intact parietal cells, CT (10(-12) 10(-8) M) caused marked stimulation of [14C]aminopyrine accumulation and cAMP production confirming the functional importance of Gs alpha in regulation of H+ production. Identical membrane preparations were preincubated (2 h, 4 degrees C) in parallel with and without RM/1, a rabbit polyclonal anti-Gs alpha-antibody. Subsequently, adenylate cyclase was stimulated by histamine, GLP-1-(7-36) amide, CT, or forskolin. At a 1:10 dilution, the antiserum completely abolished adenylate cyclase activity in response to maximal concentrations of histamine, GLP-1-(7-36) amide, and CT while reducing forskolin stimulation by only 22.0 +/- 4.9%. At 1:50, RM/1 reduced responses to histamine, GLP-1-(7-36) amide and CT by 20-30% but failed to inhibit forskolin-stimulated enzyme activity. At 1:100, the antiserum was ineffective versus all stimuli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203526 TI - Reoxygenation injury in isolated rat hepatocytes: relation to oxygen free radicals and lipid peroxidation. AB - Oxygen free radical (OFR) formation and lipid peroxidation (LP) were measured in freshly isolated perfused rat hepatocytes during 2-h reoxygenation after 2.5 h of anoxia. Superoxide anions and hydrogen peroxide (H2O2) were detected by enhanced chemiluminescence. LP and cell damage were assessed by measuring malondialdehyde (MDA) and lactic dehydrogenase (LDH) release, respectively. During anoxia, the chemiluminescence decreased to background levels and MDA remained constant, whereas LDH release increased progressively to 168 +/- 22 mU/min in 2.5 h. During reoxygenation after a 2.5-h period of anoxia, superoxide formation increased rapidly to 125 +/- 16 nA and then it declined progressively toward the control level. At the same time, H2O2 production exhibited a biphasic pattern with an initial peak reaching 78 +/- 16 nA at 15.5 +/- 1 min, followed by a slower increase to 92 +/- 14 nA during the 2nd h. LDH release increased from 168 +/- 22 to 286 +/- 32 mU/min in the first 30 min of reoxygenation and then declined toward the control rate during the 2nd h. MDA release increased continuously from 1.16 +/- 0.18 to 7.75 +/- 0.74 pmol/min. OFR generation occurred 15-30 min before the peak rise in LDH. Moreover, after shorter periods of anoxia (1-2 h), hepatocytes produced measurable amount of OFR but without a significant increase in LDH release. These results demonstrate that 1) isolated liver parenchymal cells generate measurable amounts of superoxide anions and of H2O2 during reoxygenation after 1-2.5 h of anoxia, 2) lipid peroxidation follows the formation of OFR, and 3) reoxygenation injury is correlated to OFR generation but not to lipid peroxidation. PMID- 8203527 TI - Visualization of gene expression of short and long forms of prolactin receptor in rat digestive tissues. AB - Several effects of prolactin have been characterized in various tissues of the gastrointestinal tract. In the present study, the expression of short and long forms of prolactin receptor was explored and quantified in the digestive tract and correlated to the prolactin specific functions. Sections of all digestive tissues were analyzed by in situ hybridization, using 35S-labeled oligoprobes unique to each form of receptor. Macroautoradiogram signals were quantified and expressed in arbitrary units. In rat liver, prolactin receptor mRNAs are expressed to a much greater degree in females than in males. The short-form transcript is significantly expressed to a greater degree in liver, whereas the long form predominates in the pancreas and esophagus. In the remainder of the gastrointestinal tract, there is an equivalent distribution of short- and long form transcripts. Relatively high signal intensities are seen in the stomach, duodenum, jejunum, ileum, and colon, whereas the rectum is essentially negative. The identification of prolactin receptor gene expression to limited regions should help establish specific functions associated with this hormone in the digestive tissues. PMID- 8203528 TI - Cloning and characterization of a growth factor-inducible cyclooxygenase gene from rat intestinal epithelial cells. AB - Growth factors have been shown to play a role in intestinal epithelial growth regulation and transformation. Utilizing standard differential cloning techniques, we have isolated a growth factor-inducible gene (RS-2) from rat intestinal epithelial cells that has approximately 95% homology to the mouse mitogen-inducible cyclooxygenase (COX-2) at the amino acid level. This cDNA hybridizes to a approximately 4.5-kb mRNA from transforming growth factor (TGF) alpha-stimulated rat intestinal epithelial (RIE-1) cells and is constitutively expressed in vivo in adult rat kidney and brain. Nuclear run-on experiments demonstrate that the increase of RS-2 mRNA after TGF-alpha stimulation is in part due to an increased transcription rate of the gene. The coding region for RS-2 was subcloned into a pCMV-2 expression vector, and the RS-2 protein was expressed in COS-1 cells. Microsomal fractions isolated from the COS-1 cells transfected with the RS-2 expression vector contained cyclooxygenase activity. In addition to the production of prostaglandins, the recombinant RS-2 protein also catalyzed the formation of three other eicosanoid products. In summary, we have cloned a mitogen-inducible cyclooxygenase gene from rat intestinal cells that is induced following growth factor stimulation. PMID- 8203529 TI - L-glutamine and L-asparagine stimulate Na+ -H+ exchange in porcine jejunal enterocytes. AB - L-Glutamine (Gln) is a major respiratory fuel and substrate for nucleic acid synthesis in mammalian intestinal cells. The structurally related amino acid, L asparagine (Asn), stimulates the proliferative enzyme ornithine decarboxylase in colonocytes, an effect that is blocked by the Na+-H+ exchange inhibitor amiloride. In an epithelial cell line derived from newborn piglet jejunum (IPEC J2 cells), we determined intracellular pH (pHi) by computer-assisted microfluorimetry in single cells loaded with pH-sensitive dye 2',7'-bis(2 carboxyethyl)5-(6)- carboxyfluorescein. Resting pHi in N-2-hydroxyethylpiperazine N'-2- ethanesulfonic acid-buffered NaCl Ringer was 7.06 +/- 0.02. Removal of external Na+ caused reversible acidification; recovery of pHi from NH+4-induced acid load was Na+ dependent, amiloride inhibitable, and Cl-independent. Asn and Gln had no measurable effect on resting pHi, but pretreatment with Asn or Gln induced a consistent twofold increase in pHi recovery from an acid challenge that was not seen with L-proline, D-glutamine, or L-phenylalanine. Inhibition of Gln metabolism by aminooxyacetate abolished the stimulatory effect of Gln on the exchanger. The tumor promotor phorbol 12-myristate 13-acetate (PMA) stimulated recovery rate from acid load and also increased resting pHi. The effects of PMA and Gln on Na+-H+ exchange from acid load were additive. Stimulation of Na+-H+ exchange by PMA, but not by Gln, was inhibited by protein kinase C (PKC) inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpeperazine. We conclude that Gln metabolism stimulates Na+-H+ exchange of acid-loaded porcine enterocytes by a mechanism not requiring activation of PKC. PMID- 8203530 TI - Cyclic AMP- and phorbol ester-regulated Cl- permeabilities in primary cultures of human and rabbit colonocytes. AB - Chloride transport in 24-h primary cultures of human and rabbit distal colonic crypt cells (90 +/- 5% viable) were characterized using the Cl(-)-sensitive fluorescent probe 6-methoxyquinolyl acetoethyl ester. To calculate the Cl- influx in millimolar per second, the Stern-Volmer quenching constant was determined to be 24.3 M-1 for human and 24.6 M-1 for rabbit colonocytes. Cl- influx was dependent on extracellular Cl- concentration ([Cl-]0), with maximal influx at [Cl ]0 > or = 20 mM. The adenosine 3',5'-cyclic monophosphate (cAMP)-dependent secretagogues forskolin (1 microM), prostaglandin E1 (1 microM), and 8 bromoadenosine 3',5'-cyclic monophosphate (100 microM) increased Cl- influx in human colonocytes from 0.35 +/- 0.08 to 2.14 +/- 0.65, 1.85 +/- 0.51, and 0.84 +/ 0.04 mM/s (n = 4), respectively, and in rabbit colonocytes from 0.22 +/- 0.03 to 1.04 +/- 0.11, 1.24 +/- 0.12, and 1.08 +/- 0.07 mM/s (n = 5), respectively. Depending on the secretagogue, this influx was inhibited 50-90% by the Cl- channel blocker diphenylamine-2-carboxylate (DPC; 50 microM) and > or = 65% by the Na-K-2Cl cotransport inhibitor furosemide (10 microM). Phorbol 12,13 dibutyrate, an activator of protein kinase C, increased Cl- permeability 3.8-fold in human and 2.4-fold in rabbit colonocytes. The phorbol 12,13-dibutyrate stimulated Cl- permeabilities were sensitive to DPC and furosemide but not to indomethacin. These studies demonstrate DPC and furosemide-sensitive Cl- permeabilities in isolated cultured human and rabbit colonocytes, which can be activated by cAMP and protein kinase C stimulators. PMID- 8203531 TI - Mast cell activation augments gastric mucosal injury through a leukotriene dependent mechanism. AB - Several lines of evidence suggest a role for mast cells as modulators of gastric mucosal integrity, but the effect of antigenic mast cell activation on mucosal resistance to injury has not previously been examined. In this study, rats were sensitized to the nematode Nippostrongylus brasiliensis and were studied 35-42 days later. With use of an ex vivo gastric chamber preparation, the stomach was exposed for 10 min to 20% ethanol. In some rats, antigen was administered intra arterially 10 min before application of ethanol. Sensitized rats exhibited similar levels of ethanol-induced gastric injury as control rats, despite having significantly greater numbers of mucosal mast cells. However, antigen administration, which did not in itself produce mucosal injury, significantly augmented (approximately 3-fold) the extent of injury in sensitized but not control rats. Prior treatment with dexamethasone depleted mucosal mast cells in control and sensitized rats. Moreover, this treatment abolished the increase in mucosal injury observed in sensitized rats treated with antigen and topical ethanol. Pretreatment with a leukotriene D4-receptor antagonist, but not a platelet-activating factor-receptor antagonist or a cyclooxygenase inhibitor, abolished the increased susceptibility of sensitized rats to gastric damage induced by antigen and topical ethanol. These results suggest that mucosal mast cell number per se does not influence mucosal susceptibility to injury; however, activation of mast cells markedly increases the susceptibility to injury through a peptidoleukotriene-dependent mechanism. PMID- 8203532 TI - Expression of protooncogenes c-fos and c-myc in healing of gastric mucosal stress ulcers. AB - The current study determines the hypothesis that expression of protooncogenes c fos and c-myc is involved in the mechanism of polyamine-stimulated healing in gastric mucosal stress ulcers. Rats were fasted 22 h, placed in restraint cages, and immersed in water to the xiphoid process for 2-6 h. Animals were killed either immediately after stress or at 2-h intervals up to 24 h after 6 h of stress. Stress caused both visible lesions and induction of ornithine decarboxylase (ODC) activity in the oxyntic gland mucosa after 2 h. Increased ODC activity was paralleled by increases in the mucosal polyamines putrescine, spermidine, and spermine. Exposure to stress led to appearance of c-fos mRNA and oncoprotein in the gastric oxyntic gland mucosa at 2 h and its disappearance by 4 h. Baseline expression of c-myc was enhanced significantly after 6 h of stress and remained elevated for 4 h. This change in the expression of c-fos and c-myc mRNA and oncoprotein preceded an increased rate of [3H]thymidine incorporation into mucosal DNA. Administration of alpha-difluoromethylornithine (DFMO, 500 mg/kg ip) totally prevented the marked increases in ODC activity and polyamine levels. DFMO also completely inhibited the expression of c-fos and significantly decreased c-myc mRNA and oncoprotein in the gastric mucosa of stressed rats. The healing process, which was significant by 12 h, was markedly inhibited by DFMO. These results show that 1) mucosa exposed to stress exhibits increased expression of c-fos and c-myc following increased polyamine synthesis and 2) inhibition of polyamine biosynthesis by DFMO decreases both protooncogene expression and mucosal healing. PMID- 8203533 TI - Regulation of glucose-dependent insulinotropic peptide gene expression by a glucose meal. AB - Glucose-dependent insulinotropic peptide (GIP) enhances insulin secretion by pancreatic beta-islet cells. Its release has been demonstrated predominantly after the ingestion of carbohydrate and fat. We have recently cloned a rat intestinal GIP cDNA and in the present studies have used this cDNA as a probe for measuring rat duodenal GIP mRNA after nutrient administration. Rats were fasted overnight, after which they were permitted to drink water or 10% glucose. The duodenum was then removed, GIP mRNA was measured by Northern hybridization analysis, and duodenal mucosa and serum GIP levels were determined by radioimmunoassay. In response to oral 10% glucose, duodenal mucosal GIP mRNA concentrations increased from 2 to 4 h, and at the end of 4 h a threefold increase was detected. Serum and mucosal GIP concentrations increased earlier, starting at 60 min, and levels remained elevated at 4 h. In separate studies, nuclear run-on assays were performed to compare the effects of glucose and water ingestion on transcription of the GIP gene. Whereas no increase in GIP gene transcription was detected in rats ingesting water, the rate of transcription doubled in glucose-fed rats. Actin gene transcription was nearly identical in both groups, indicating genomic specificity. The results of these studies indicate that duodenal GIP gene expression is stimulated at both the pre- and posttranslational levels by glucose-containing meals. These studies further suggest that the release of GIP from cellular storage granules might account for the initial increase in serum GIP levels after oral glucose ingestion. PMID- 8203534 TI - Maintenance of cellular acidification in cyanide-treated hepatocytes results from inhibition of Na+/H+ exchange. AB - Inhibition of respiration by metabolic inhibitors or hypoxia is accompanied by intracellular acidification. Although this acidification is known to promote cell survival during hypoxia, little is known about its mechanism. Given that the Na+/H+ exchanger is known to be a major component of pH regulation in normal hepatocytes, the aim of this study was to determine the effects of inhibition of mitochondrial respiration on intracellular pH (pHi) regulation and Na+/H+ exchange. Cyanide (CN-; 5 mM) plus fructose (20 mM) were used as a model of hypoxic acidosis. pHi was measured with quantitative fluorescence microscopy of cells loaded with the pH indicator, 2',7'-bis-(2-carboxyethyl)-5,6 carboxyfluorescein. In control cells, pHi was 7.09 +/- 0.01 SE (n = 106). After 60 min in CN(-)-fructose, pHi fell to 6.74 +/- 0.01 (n = 129, P < 0.001). The pHi recovery rate (expressed as mmol H+.l-1.min-1) was determined under both conditions after acid loading by transient exposure and removal of 20 mM NH4Cl. Control and CN(-)-treated cells recovered at 3.59 +/- 0.25 (n = 42) and 0.69 +/- 0.09 (n = 38, P < 0.001), respectively. Amiloride treatment (1 mM) in the absence of CN- reduced pHi recovery similarly to that caused by CN- (0.34 +/- 0.07, n = 14). CN(-)-treated cells exposed to amiloride demonstrated no additional inhibition (efflux rate 0.65 +/- 0.11, n = 27), suggesting that the inhibition is directed at Na+/H+ exchange. Twenty minutes after CN- removal, CN(-)-treated cells regained their ability to recover from an acid load, thus demonstrating the reversibility of this effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203535 TI - Pleiotropic effect of LEC mutation: a rodent model of Wilson's disease. AB - Metabolic studies with 67Cu were undertaken to identify the site of the cellular defect in copper metabolism in the Long-Evans Cinnamon (LEC) rat. The apparent rate of copper uptake by LEC primary hepatocytes was increased [maximal velocity (Vmax) = 259 pmol.min-1.mg protein-1] compared with controls (Vmax = 161 pmol.min 1.mg protein-1); however, Michaelis-Menten constant (Km) values were comparable (11.8 and 12.7 microM, LEC and control, respectively). Efflux of copper from LEC and control hepatocytes was similar from 0 to 15 min, but was reduced from 15 to 60 min in the former. Although hepatic copper contents were markedly elevated in LEC rats compared with controls (658 +/- 199 vs. 21.5 +/- 6.6 micrograms/g dry wt), biliary copper concentration was reduced in LEC rats compared with controls (0.187 vs. 1.39 +/- 0.66 microgram/ml). Subcellular fractionation of LEC liver homogenates revealed approximately 75% of copper to be present in cytosol, with gradients of copper concentration from cytosol to either lysosome or microsomal subcellular fractions. LEC rat bile and hepatic microsome and lysosome fractions contained smaller fractions of 67Cu administered intravenously as cupric acetate compared with control rats. However, recovery of 67Cu in bile and in lysosomal subcellular fractions were similar for LEC and controls following administration of 67Cu-labeled asialoceruloplasmin, which is targeted to lysosomes. This discordance suggests a possible defect in the entry of copper into lysosomes but normal delivery of lysosomal copper to bile. Based on these findings, we conclude that the mutation in LEC rats alters copper transport at more than one cellular site. PMID- 8203536 TI - Rat pancreatic lipase and two related proteins: enzymatic properties and mRNA expression during development. AB - We report the cDNA sequences of rat colipase, rat pancreatic lipase (rPL), and a rat pancreatic lipase-related protein (rPLRP). Comparison to the human PLRP cDNA suggests that the isolated clone encodes rPLRP-2. Both cDNA and a third cDNA encoding rPLRP-1 are secreted from Sf9 cells infected with recombinant baculovirus. rPL and rPLRP-2 hydrolyze triolein, 8.0 and 4.4 mumol.min 1.microgram-1, respectively. They are inhibited by bile salts, and activity is restored by (pro)colipase. PLRP-1 has barely detectable activity against triolein, even with (pro)colipase present. The pattern of mRNA expression during development in the rat reveals that all mRNA are low in the fetal rat pancreas. Both PLRP mRNA rise just before birth to a maximum 12 h after birth. They fall to low levels in the adult. In contrast, the PL mRNA is low at birth and rises rapidly during the suckling-weanling transition. In conclusion, the rat has at least three genes encoding different lipases, and these related genes have separate regulatory controls. PMID- 8203537 TI - Modulation of secretagogue-induced chloride secretion by intracellular bicarbonate. AB - We have previously demonstrated inhibition of basal Cl- secretion by intracellular bicarbonate concentration ([HCO3-]i) in rat distal colon. We now examined whether secretagogue-induced Cl- secretion is inhibited by [HCO3-]i as well. Stripped segments of distal colon from male Sprague-Dawley rats and the colon tumor cell line T84 were studied. Flux measurements were performed in the Ussing chamber under short-circuit conditions. [HCO3-]i was calculated from intracellular pH (pHi) values that were estimated with the pH-sensitive dye 2',7' bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) and carbachol were used as secretagogues. In both distal colon and T84 cells, [HCO3-]i did not affect cAMP-induced Cl- secretion. However, carbachol-induced secretion was inhibited by [HCO3-]i; in rat colon, Cl- secretion decreased from 2.3 to 1.5 mueq.cm-2.h-1 when [HCO3-]i was increased from 15.0 to 28.4 mM (P < 0.05). In T84 cells, the change in short-circuit current decreased from 8.1 to 1.1 microA/cm2 over a range of [HCO3-]i from 0 to 15.6 mM (P < 0.001). We conclude that [HCO3-]i is an important modulator of carbachol-stimulated Cl- secretion in both rat distal colon and the T84 cell line. cAMP-mediated secretion is not affected by [HCO3-]i. PMID- 8203538 TI - Absorption of platelet-activating factor acetylhydrolase by rat intestine. AB - Platelet-activating factor acetylhydrolase (PAF-AH) is a 43-kDa protein that catalyzes the degradation and inactivation of this potent phospholipid mediator. PAF plays an important role in the pathogenesis of necrotizing enterocolitis (NEC), and the elevation of the plasma PAF-AH activity may be beneficial in the prevention of this disease. The activity of PAF-AH was transferred from the mucosal to the serosal fluid in intestinal sacs from neonatal rats. Translocation was highest on day 15, decreased by day 21, and disappeared by day 24. Greater transport of the enzyme was noted in the neonatal jejunum compared with duodenum or ileum. PAF-AH absorption in 15-day-old rats was decreased by the addition of inhibitors of energy production and by low temperature. We have, therefore, concluded that the enzyme transport is an energy-dependent process. It is suggested that PAF-AH found in milk may prove to be beneficial in the prevention of NEC by its translocation across the intestinal mucosa. The absorption of macromolecules in the neonate, in addition to providing a passive immunity, may also serve a protective role by inactivating certain proinflammatory agents, such as PAF. PMID- 8203539 TI - Stimulation of duodenal motility by hyperosmolar mannitol depends on local osmoreceptor control. AB - Duodenal motility is stimulated by hyperosmolar solution. Since intestinal distension also stimulates intestinal motility, this increase in the motility response may be due to either stimulation of duodenal local osmoreceptor control or intestinal distension resulting from osmotic equilibration. To test which mechanism is primarily responsible for this osmotically sensitive effect, we compared the number of duodenal spike bursts in five dogs equipped with duodenal fistulas that allowed for the preservation or removal of intestinal distension. The response to 300 vs. 1,200 mosM mannitol was compared under three experimental perfusion methods: 1) distension was preserved both proximal and distal to the fistula (DD); 2) distension proximal to the fistula was removed (rD); and 3) distension both proximal and distal to the fistula was removed (rr). The test solutions had access to either the whole gut (DD and rD) or only the first 10 cm of the duodenum (rr). We found that 1) there were more spike bursts after the hyperosmolar solution (dose effect, P < 0.05, analysis of variance); 2) there was no significant difference between the three experimental methods; and 3) the stimulating effect of hyperosmolar solution depended on the first 10 cm of the duodenum. Thus, since hyperosmolar solution increased duodenal motility regardless of whether intestinal distension was preserved or removed, the stimulating effect of hyperosmolar solution on duodenal motility was primarily the result of a local osmoreceptor control mechanism located in the first 10 cm of the duodenum. PMID- 8203540 TI - Secretion and distribution of rat intestinal surfactant-like particles after fat feeding. AB - Triacylglycerol feeding increases serum intestinal alkaline phosphatase (IAP) activity and leads to the appearance of an alkaline phosphatase-containing particle in the luminal washings over the apical surface of the rat enterocyte and in the blood (J. Clin. Invest. 84: 1355-1361, 1989). To examine the coordinate appearance of these particles and the enzyme and to follow their distribution in vivo after feeding, an enzyme-linked immunoabsorbent assay (ELISA) was developed, using antisera raised against the purified intact surfactant-like particle. Tissue compartments that were examined for phosphatase activity and particle content included isolated enterocytes, lamina propria, intestinal luminal washings, and serum. Alkaline phosphatase activity peaked earliest in the lamina propria (3 h), followed by the enterocyte and the luminal washings (5 h) and serum (7 h). Surfactant-like particle content peaked in the enterocyte and lamina propria at 3 h, followed by the serum (3-5 h) and the luminal washings (5 h). The buoyant density of the particle in the enterocyte (d = 1.08-1.09) and serum (d = 1.07-1.08) after fat feeding was similar to that of the isolated particle (d = 1.07-1.08). The density of particle proteins detected by ELISA in fasted serum was more diffuse and > 1.10, consistent with partial degradation of the particle and/or its proteins. These data confirm that the particle and its bound IAP are secreted from the enterocyte after triacylglycerol feeding and that they appear in compartments adjacent to both the basolateral (serum) and apical (luminal wash) surfaces of the enterocyte.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203541 TI - Increase in oxygen uptake due to arachidonic acid is oxygen dependent in the perfused liver. AB - The purpose of this study was to determine whether the effect of arachidonic acid on hepatic O2 uptake is O2 dependent and which region of the liver lobule it affects. In livers perfused at normal flow rates, infusion of arachidonate increased O2 uptake significantly by about 20-25 mumol.g-1.h-1. When the flow rate was doubled to make the hepatic O2 gradient shallower, the increase in O2 uptake due to arachidonate was two to three times larger (i.e., approximately 50 mumol.g-1.h-1). In livers perfused in the retrograde direction, maximal rates of O2 uptake were about twofold higher in upstream pericentral than in downstream periportal regions, and arachidonic acid nearly doubled O2 uptake in downstream areas without affecting rates in upstream regions. Thus it is concluded that arachidonate stimulates O2 uptake in an O2-dependent manner. This effect was sensitive to an inhibitor of the lipoxygenase, nordihydroguaiaretic acid, in perfused liver but not in isolated hepatocytes. In addition, conditioned medium from Kupffer cells incubated at high O2 tension stimulated parenchymal cell O2 uptake. Furthermore, arachidonate increased intracellular Ca2+ in isolated Kupffer cells in a dose-dependent manner. These findings suggest that eicosanoids produced by nonparenchymal cells participate in a hepatic O2 sensor mechanism involving Ca2+ that regulates O2 uptake by parenchymal cells in the liver. PMID- 8203542 TI - Does laser-Doppler flowmetry provide a quantitative measure of hepatic perfusion? PMID- 8203543 TI - Immune sensitization augments epithelium-dependent spontaneous tone in guinea pig trachealis. AB - We examined epithelial modulation of tracheal smooth muscle (TSM) responsiveness in vitro from guinea pigs receiving active immune sensitization in vivo. Initially, guinea pigs were either ovalbumin sensitized (by aerosol) or sham sensitized with normal saline; TSM responsiveness was assessed isometrically as active tension (AT) after equilibration by electrical field stimulation in vitro. For epithelium-intact (Epi+) tissues, sensitization caused an increase in baseline active spontaneous tone (1.89 +/- 0.20 g AT) vs. sham-sensitized tissues (1.18 +/- 0.28 g AT; P = 0.02). Spontaneous tone in sensitized TSM in which the epithelium was removed (Epi-) (1.01 +/- 0.14 g AT) was substantially less than from Epi+ tissues (P = 0.01) and did not differ from sham-sensitized epithelium denuded tissues (0.82 +/- 0.24 g AT; P > 0.05). Indomethacin caused a reduction in spontaneous tone to comparable magnitude for all treatment paradigms. Immune sensitization caused physiological reduction in the ability to relax in response to isoproterenol; the concentration of isoproterenol eliciting 50% relaxation of spontaneous tone was 7.10 +/- 0.13 (-log M) for TSM from sensitized guinea pigs compared with 8.20 +/- 0.27 (-log M) for sham-sensitized tissues (P = 0.006). However, after precontraction with exogenous acetylcholine, relaxation caused by isoproterenol was not affected by either indomethacin or epithelial removal. Muscarinic responsiveness to acetylcholine was augmented by immune sensitization; however, the increase in response to acetylcholine was attenuated by epithelium removal or cyclooxygenase blockade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203544 TI - Neuropeptide Y and norepinephrine cooperatively inhibit human tracheal gland cell secretion. AB - The effects of neuropeptide Y (NPY) and norepinephrine (NE) on the secretion of human tracheal gland (HTG) cells in culture were examined using the bronchial inhibitor (BrI) as a secretory marker. NPY by itself provoked no change in secretion, neither in intracellular Ca2+ nor in adenosine 3',5'-cyclic monophosphate (cAMP) levels. NE induced transient intracellular Ca2+ mobilization and an increase of intracellular cAMP and also, as previously described, a short time concentration-dependent decrease of BrI secreted by HTG cells. When applied together on HTG cells, NPY and NE induced an increase of intracellular cAMP, a discrete sustained increase of basal intracellular Ca2+, and a long-lasting inhibition of secretion. Our data suggest that NPY acts for human tracheal gland cells as a NE neuromodulator rather than as a neurotransmitter. Thus culture of HTG cells appears to be an interesting pharmacological support for studying inhibition of bronchial secretion and could be applied in the study of pathologies where hypersecretion is observed, such as cystic fibrosis. PMID- 8203545 TI - Human SP-A: genotype and single-strand conformation polymorphism analysis. AB - We have previously characterized two surfactant protein A (SP-A) cDNAs termed 1A and 6A, as well as a 6A allelic variant termed 6A1. These sequences are quite heterogeneous at the 3' untranslated region (3'UT). Differences between 6A and 6A1 alleles include an 11-bp insertion/deletion 407 bases downstream from the start of the translation termination codon and a base pair polymorphism (C or G) in exon 1 (position 1,193; White, Damm, Miller, Spratt, Schilling, Hawgood, Benson, and Cordell. Nature Lond. 317: 361-363, 1985). The 11-bp (GCCCACTGCCT) segment is present in 6A1 and absent in 6A. The 6A/6A genotype, in a small number of specimens, showed a trend toward a higher frequency in the black Nigerian population compared with Caucasians. In this report, we examine the frequency of the 6A genotype in a larger number of samples from Caucasians and black Nigerians as well as the meiotic stability of the 3'UT heterogeneity. Slot-blot analysis and allele-specific oligonucleotide probes have confirmed that the 6A/6A genotype is more frequent in the Nigerian population. Single-strand conformation polymorphisms in the 3'UT appear to be stably inherited by members of a three generation family, suggesting that these nucleotide variants represent natural polymorphisms in the population. PMID- 8203546 TI - Contraction and depolarization induced by fetal bovine serum in airway smooth muscle. AB - We investigated the effects of fetal bovine serum (FBS) on the resting membrane potential and muscle tone of canine airway smooth muscles using tension recording and microelectrode methods. At concentrations > 0.1%, FBS induced a sustained increase in muscle tone. At concentrations > 1%, FBS depolarized the resting membrane potential of dog trachea in a dose-dependent manner. When FBS was dialyzed, it failed to induce a sustained increase in muscle tone or to depolarize the membrane, indicating that FBS contained factor(s) that induced contraction of dog airway smooth muscles. When FBS was dialyzed against distilled water, the outer solution which was freeze dried and then reconstituted (> 1% in original vol) induced a sustained increase in muscle tone, indicating that FBS contained dialyzable factor(s) that increased muscle tone and depolarized the resting membrane potential of dog airway smooth muscles. Methysergide (10(-6) M) or cyproheptadine (10(-6) M), nonspecific antagonists to serotonin receptors, 5 hydroxytryptamines (5-HT1 and 5-HT2), markedly reduced the FBS-induced increase in the muscle tone to approximately 20% of the original value but did not abolish the response. On the other hand, methysergide (10(-6) M) completely suppressed the increase in the muscle tone evoked by peak fractions obtained by application of the dialysate of FBS or 5-HT to a C18 reverse-phase column, indicating the peak fractions contained only 5-HT. These observations indicate that FBS contained 5-HT and an unknown factor(s) responsible for increase in the muscle tone of the airway smooth muscle induced by FBS. PMID- 8203547 TI - Effect of endocytosis inhibitors on alveolar clearance of albumin, immunoglobulin G, and SP-A in rabbits. AB - Protein in the alveolar space may be cleared by endocytosis and degradation inside alveolar epithelial cells, by transcytosis across the alveolar epithelium, or by restricted diffusion through the epithelium. The relative contributions of these three pathways to clearance of large quantities of protein from the air spaces is not known. This study investigated the effects of monensin and nocodazole, agents which inhibit endocytosis in cell culture, on alveolar epithelial protein transport in anesthetized rabbits. There was evidence that monensin and nocodazole inhibited endocytosis by the alveolar epithelium in vivo. Nocodazole increased the number of vesicles in the alveolar epithelium and capillary endothelium. Monensin increased vesicle density in the endothelium. These results suggested that the inhibitors disrupted microtubules or interrupted cellular membrane traffic in the lung. Both inhibitors decreased lung parenchymal uptake of immunoreactive human albumin from the air spaces. Monensin and nocodazole inhibited albumin uptake in cultured alveolar type II cells. Monensin increased the amount of 125I-labeled surfactant protein A associated with the lungs, compared with the quantity remaining in the air space 2 h after instillation. Although the drugs decreased alveolar epithelial protein uptake, they did not decrease alveolar clearance of 125I-labeled immunoglobulin G or 131I labeled albumin in anesthetized rabbits. Thus monensin- and nocodazole-sensitive protein-uptake pathways do not account for most alveolar protein clearance when the distal air spaces are filled with a protein solution. PMID- 8203548 TI - Increased endothelin receptor gene expression in hypoxic rat lung. AB - Our previous studies demonstrated that exposure to hypoxia increases pulmonary artery pressure and plasma endothelin-1 (ET-1) levels and selectively enhances ET 1 gene expression in rat lung. The current study examined the effects of hypoxia (48 h, 10% O2, 1 atm) on ET-1 and endothelin A (ETA) and ETB receptor steady state mRNA levels in lung, heart, pulmonary artery, thoracic aorta, superior vena cava, kidney, spleen, and liver of the rat. In lung, hypoxic exposure was associated with significant increases in ET-1 mRNA (4.1-fold), ET-1 peptide (1.5 fold) and ETA mRNA (2.3-fold) levels; ETB mRNA levels were unchanged. ET-1 mRNA was increased in response to hypoxia in pulmonary artery but not in aorta; both ETA and ETB receptor steady-state mRNA levels were increased in thoracic aorta, left atrium, and right ventricle, and tended to be increased in right atrium of hypoxia-exposed rats, compared with air controls. ETB but not ETA receptor steady state mRNA levels were increased in pulmonary artery of hypoxia-exposed rats. No change in expression of either ET receptor steady-state mRNA levels was seen in organs perfused by the systemic vascular bed. In no case were ET receptor mRNA levels in hypoxic rats reduced below air control levels, despite elevations in local and/or circulating ET-1. These findings are consistent with a role for ET 1, acting through ETA receptors, in the pathogenesis of hypoxia-induced pulmonary hypertension. PMID- 8203549 TI - Recombinant GM-CSF reduces lung injury and mortality during neutropenic Candida sepsis. AB - Cyclophosphamide (CY)-induced neutropenia exacerbates septic shock and acute lung injury during Candida albicans (CA) fungemia in conscious rats. We hypothesized that treatment of such animals with recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) improves host defense during disseminated candidiasis by increasing peripheral neutrophils (PMNs) and enhancing endogenous production of antifungal cytokines including tumor necrosis factor-alpha (TNF). Naive (neutrophil-replete) or neutropenic rats were infected with 10(7) yeast phase CA; subgroups received GM-CSF (25 micrograms/kg sc) or sterile 0.9% NaCl (NS) twice a day beginning 3 days before CA infection. Arterial hemodynamics, formed blood elements, bioactive TNF in serum and bronchoalveolar lavage fluid (BALF), and lung histopathology were monitored for up to 72 h after infection. All naive animals receiving GM-CSF (n = 5) and 78% of naive rats given NS (n = 9) remained normotensive through 72 h with no lung injury, differing principally in baseline PMNs before CA infection (8.8 +/- 1.8 x 10(3)/microliters, mean +/- SE, vs. 3.7 +/- 0.4 x 10(3)/microliters, respectively, P < 0.01). Neutropenic rats given NS (baseline PMN = 41 +/- 10/microliters, n = 7) were sensitized to CA, and 100% died of hypothermic shock with severe respiratory distress within 56 h of infection. Pulmonary periarterial and alveolar hemorrhage were prominent. Although GM-CSF did not increase baseline PMNs in CY animals by the outset of infection (162 +/- 58/microliters, n = 8), 62% of these rats remained normotensive and eupneic through 72 h (P < 0.01), and their lungs showed no perivascular hemorrhage, alveolar disruption, or fungi.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203550 TI - Calpain-induced downregulation of activated protein kinase C-alpha affects lung epithelial cell morphology. AB - A few minutes after mouse lung epithelial cell lines were treated with 12-O tetradecanoylphorbol-13-acetate (TPA), the cells rounded up and pulled away from their neighbors. Several hours later, the cells flattened out to resume their original morphology. To begin to characterize the enzymology underlying these changes, the subcellular distribution and intracellular content of the TPA receptor, protein kinase C (PKC), and its putative endogenous regulator, the Ca(2+)-dependent protease, calpain, were investigated. Of eight PKC isozymes examined in several tumorigenic and nontumorigenic cell lines, all cells contained PKC-alpha, PKC-delta, and PKC-zeta. TPA rapidly (5 min) translocated PKC-alpha from the cytosol to the particulate fraction; PKC-alpha concentrations then decreased with continued TPA exposure. PKC-zeta levels and intracellular location were not affected. An inhibitor of PKC activity, GF 109203X, prevented the initial morphological change. The calpain II isozyme was also found in all cell lines, and its cellular content increased as a result of TPA treatment. Calpain inhibitor I did not affect the initial shape change but prevented subsequent flattening of the cells. We therefore conclude that PKC activation is required for the TPA-induced alterations in lung cell morphology and that calpain mediates the return to a flattened epithelial appearance. PMID- 8203551 TI - Active sodium transport and alveolar epithelial Na-K-ATPase increase during subacute hyperoxia in rats. AB - Active Na+ transport and lung edema clearance were studied in a model of lung injury caused by sublethal oxygen exposure. Rats exposed to 85% O2 for 7 days were studied at 0, 7, 14, and 30 days after removal from the hyperoxic chamber and compared with room air controls. In the isolated-perfused, fluid-filled rat lung, albumin flux from the perfusate into the air spaces increased after oxygen exposure and returned to control values after 7 days of recovery. However, permeability to small solutes (Na+ and mannitol) normalized only after 30 days of recovery from hyperoxia. Active Na+ transport increased immediately after oxygen exposure and returned to control values 7 days after removal from hyperoxic chamber. Na-K-adenosinetriphosphatase (ATPase) activity, and protein expression in alveolar epithelial type II cells obtained at the end of the isolated lung experiments increased significantly after the oxygen exposure compared with controls in association with the increased active Na+ transport. We conclude that active Na+ transport and lung liquid clearance are increased in the subacute hyperoxic phase of lung injury in rats, due in part to the upregulation of alveolar epithelial Na-K-ATPases. Conceivably, this behavior protects against the effects of lung injury by allowing the injured lung to clear edema more effectively. Accordingly, this upregulation may be targeted as a strategy to diminish edema in patients with lung injury. PMID- 8203552 TI - Sodium excess aggravates hypertension and renal parenchymal injury in rats with chronic NO inhibition. AB - Chronic nitric oxide (NO) inhibition promotes hypertension and ischemic glomerular injury with only minor glomerulosclerosis (GS). We evaluated the effect of superimposed salt overload, which has been shown to aggravate GS in other models. Fifteen days of treatment with the NO inhibitor N omega-nitro-L arginine methyl ester (L-NAME) promoted marked arterial and glomerular hypertension, hyporeninemia, and slight renal interstitial expansion, but no glomerular injury. Salt overload slightly exacerbated systemic and glomerular hypertension, promoted albuminuria, interstitial expansion, and glomerular ischemia, and paradoxically reversed hyporeninemia. The angiotensin II inhibitor losartan attenuated glomerular and systemic hypertension and prevented renal injury in these rats. Thirty days of treatment with L-NAME resulted in marked hypertension, hyperreninemia, interstitial expansion, and glomerular ischemia. Concomitant salt overload exacerbated hypertension, interstitial expansion, and ischemia and promoted massive albuminuria, GS, and creatinine retention. Losartan attenuated these effects. Sodium overload aggravates the renal and systemic consequences of chronic NO inhibition by mechanisms that may include paradoxical activation of renin secretion. Interstitial expansion and glomerular ischemia, rather than GS, constitute the chief modalities of renal injury in this model. PMID- 8203553 TI - Impaired homologous upregulation of vitamin D receptor in rats with chronic renal failure. AB - We studied the homologous regulation of the vitamin D receptor (VDR) in the duodenum of rats with chronic renal failure. Mean basal nuclear 3H-labeled 1 alpha,25-dihydroxyvitamin D3 ([3H]1,25(OH)2D3) binding capacity was 48 and 43 fmol/mg protein for sham-operated and uremic rats with similar dissociation constants (Kd), respectively. These results coincided with those of immunoblot analysis, which found that VDR protein level of uremic rats was 87.6% that of sham-operated rats. In uremic rats, 1,25(OH)2D3, 2.0 micrograms/kg, failed to upregulate VDR protein levels until 24 h, in contrast to the significant increases produced in sham-operated rats at both 12 (1.55-fold) and 24 h (1.75 fold). Baseline level of VDR mRNA in uremic rats, determined by Northern blot analysis, was comparable to that in sham-operated rats. Treatment with 1,25(OH)2D3 slightly decreased VDR mRNA at 6-24 h in the sham-operated rats, in contrast to the increase seen at 6 h in uremic rats. These results suggest that the homologous upregulation of VDR was attenuated in rats with chronic renal failure because of an impairment at a translational and/or posttranslational step. PMID- 8203555 TI - Long-term regulation of collecting duct water permeability: freeze-fracture analysis of isolated perfused tubules. AB - Terminal inner medullary collecting duct (IMCD) segments from water-restricted rats have high osmotic permeabilities despite the absence of vasopressin (AVP). We performed freeze-fracture analysis of individual IMCD segments from such animals following measurement of their water permeability (Pf). IMCD segments from control rats did not have a high Pf in the absence of AVP (88 +/- 15 microns/s) and had a low incidence of E-face intramembrane particle (IMP) clusters (9.6 +/- 2.7 clusters/100 microns 2). Segments exposed to 0.1 nM AVP in vitro had enhanced Pf (1,060 +/- 210 microns/s) and cluster incidence (122 +/- 33 clusters/100 microns 2). IMCD segments isolated from rats dehydrated for 48 h and perfused without AVP exposure had an elevated Pf (605 +/- 71 microns/s) and a high incidence of clusters (166 +/- 36 clusters/100 microns 2). There also was an increase in the number of single particles between clusters in tubules from dehydrated rats (2.5-fold) and in AVP-treated tubules (3.6-fold). These findings indicate that IMP clusters are associated with high water permeability in tubules from dehydrated animals independent of continued AVP exposure. The increased incidence of particles between clusters suggests that water channels may also occur outside of cluster domains. PMID- 8203554 TI - Interleukin-1 alpha stimulates KC synthesis in rat mesangial cells: glucocorticoids inhibit KC induction by IL-1. AB - To assess the possible role of the production of chemokines by intrinsic glomerular cells in the generation of inflammation in glomerulonephritis, the chemokine, KC, was cloned from a rat macrophage cDNA library. Transfection of rat KC into COS-7 cells resulted in increased neutrophil chemotactic activity. The KC cDNA was expressed as a fusion protein in Escherichia coli for generation of an antibody. By using a riboprobe derived from the cDNA and the antibody, interleukin-1 (IL-1) was found to induce the expression of KC in rat mesangial cells. The induction of KC by IL-1 could be inhibited by dexamethasone (DEX). The protein synthesis inhibitor cycloheximide reversed the DEX-mediated inhibition, which suggested that new protein synthesis was necessary for the inhibitory effect. A nuclear runoff analysis indicated that DEX inhibited the transcription of KC induced by IL-1. The stability of KC mRNA was not decreased in the presence of DEX. Furthermore, immunoblots showed that DEX also inhibited KC expression at the level of translation. Together the inhibition of transcription and translation of the KC gene by DEX contribute to decreased KC expression in mesangial cells. The finding that mesangial cells express KC in response to proinflammatory cytokines, such as IL-1, points to a central role for the mesangial cell as a chemotactic source in glomerular inflammation. PMID- 8203556 TI - Renal function in hypertensive rats transgenic for mouse renin gene. AB - The recent development of a transgenic rat strain carrying the mouse ren-2 renin gene [TGR(mRen2)27] has provided a new model of hypertension characterized by suppressed plasma renin levels and marked hyperproreninemia. In this long-term study, we examined the kidney function of these animals. Transgenic rats had significantly (P < 0.01) higher blood pressures than control animals at 2, 4, and 8 mo of age. However, the severity of their hypertension diminished over time (225 +/- 8 mmHg at age 2 mo vs. 169 +/- 5 mmHg at age 8 mo, P < 0.001), indicating age-dependent transgene regulation. Whole kidney and single-nephron blood flows and glomerular filtration rates did not differ between control and TGR(mRen2)27 animals studied with micropuncture techniques at 4 and 8 mo of age. Preglomerular vasoconstriction was responsible for this normal autoregulatory response. Elevated preglomerular vascular resistance of transgenic rats prevented transmission of systemic hypertension to glomeruli at 4 but not 8 mo of age leading to increased glomerular capillary pressures in these older animals (53 +/ 1 vs. 48 +/- 1 mmHg, P < 0.05). Pathological albuminuria appeared as early as 2 mo of age but did not increase over the subsequent 6 mo of follow-up. The incidence of glomerulosclerosis, assessed at 4 and 8 mo of age, was greater in TGR(mRen2)27 than control animals (6.6 +/- 1.4% vs. 0.9 +/- 0.3%, P = 0.01) but did not differ between 4- and 8-mo-old transgenic rats. Glomerular ultrafiltration coefficients were significantly elevated (P < 0.05) in transgenic rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203557 TI - Role of renal nerves for the expression of renin in adult rat kidney. AB - Utilizing a combination of mechanical and chemical unilateral denervation, we have examined the relevance of renal innervation for the expression of renin in kidneys of adult rats. Renal denervation led to a reduction by 57 +/- 4% of renin containing areas in denervated kidneys as quantitated by morphometry of kidney sections immunoreactive against a polyclonal antirenin antibody. Preprorenin mRNA content in the denervated kidneys fell to 46 +/- 7% of the contralateral innervated kidneys. Treatment of rats with the beta 1-adrenoreceptor antagonist metoprolol (100 mg.kg-1.day-1) for 2 days decreased renal renin mRNA levels to 71% of control levels. Unilateral renal denervation led to a further decrease of renin mRNA levels also in metoprolol-treated animals to 60% of the values found in the contralateral kidneys. Hypotensive hemorrhage led to a 1.4-fold increase of renin mRNA in the kidneys of sham-treated animals. In unilaterally denervated rats renin mRNA increased to levels similar to those in sham-operated animals in both denervated and in contralateral innervated kidneys in response to bleeding. As a consequence, the ratio of abundance of renin mRNA in the denervated to the innervated kidneys rose to 86 +/- 7%. Pretreatment of the animals with metoprolol, on the other hand, prevented the rise of renin mRNA in response to hypotensive hemorrhage. Our findings suggest that in the adult organism renal neural input significantly contributes to the expression of renin under basal conditions, while it appears to be of less importance for stimulation of renin gene expression by severe blood loss. PMID- 8203558 TI - Glomerular response to acute protein load is not blunted by high-protein diet or nephron reduction. AB - Inulin clearance (CIn) was measured in the presence of varying degrees of renal excision (NX, 0-85% of renal mass by weight), in anesthetized rats fed on high protein (HP, 30%), median-protein (MP, 10%), or low-protein (LP, 7%) diets, before and during amino acid (AA) infusion or before and after an intragastric protein load. CIn was higher in rats fed HP than in rats fed LP in controls (3.4 vs. 2.1 ml/min) and in rats with NX up to 70% after feeding for 3 wk (1.4 vs. 0.7 ml/min) or 4 days (1.5 vs. 1.1 ml/min). The difference decreased from 0% to 70% NX, and disappeared when NX exceeded 70%. Acute AA infusion and intragastric loads always increased CIn with wide individual variations. The increase was greater in rats fed HP than in rats fed MP and LP (+1.4 vs. 0.8 and 1.1 ml/min for 0% NX), diminished with greater NX (0.7 vs. 0.2 and 0.4 ml/min for 70% NX), and was very small for NX above 70%. However, when expressed as the percent of baseline values, the mean CIn increment after acute stimulation remained constant (30-45%), regardless of renal ablation and of diet. Thus preexisting hyperfiltration resulting from diet or from renal ablation does not suppress the glomerular response to an acute protein load, and acute loads afford no advantages over baseline glomerular filtration rate (GFR) measurements. By contrast, chronic protein feeding increases GFR only when nephron loss is not too severe. PMID- 8203559 TI - Protein restriction sequentially induces new urea transport processes in rat initial IMCD. AB - We reported that feeding rats 8% protein for 4 wk induces two new urea transport processes in initial inner medullary collecting ducts (IMCD); neither is present in rats fed 18% protein. In this study, we measured the time course of induction of these transporters in perfused initial IMCD segments from rats fed 8% protein. Net urea flux was induced after 3 wk, whereas vasopressin-stimulated passive urea permeability (P(urea)) was induced after 2 wk. 8-Bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) significantly increased P(urea)); adding vasopressin did not increase P(urea) further. In fact, there was no difference in vasopressin stimulated cAMP production in initial or terminal IMCD segments from rats fed 18% or 8% protein, suggesting that the adaptive response was not due to increased cAMP production. Glucagon did not change cAMP production or P(urea). Specificity of the response was suggested because neither aldose reductase nor sorbitol dehydrogenase activity changed with feeding 8% protein. Thus 1) in initial IMCD segments, vasopressin-stimulated P(urea) is induced after 2 wk, but net urea flux requires 3 wk of feeding 8% protein; 2) this adaptation is not solely due to a higher rate of cAMP production; and 3) specificity of the adaptive response is suggested because activities of enzymes responding to decreases in concentrating ability are unchanged. These results suggest that two distinct urea transporters may be involved in the adaptation to a low-protein diet. PMID- 8203560 TI - Inhibition of nitric oxide causes exaggerated natriuresis in spontaneously hypertensive rats. AB - Competitive inhibition of the conversion of L-arginine to nitric oxide by a high dose of NG-monomethyl-L-arginine (L-NMMA) leads to significant increases in arterial pressure, natriuresis, and diuresis in Sprague-Dawley rats. The purpose of this study was to determine the extent of the natriuretic and diuretic responses and the possible role of arterial pressure and renal interstitial hydrostatic pressure (RIHP) elevations with the infusion of L-NMMA in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Intravenous infusion of L-NMMA (15 mg/kg bolus followed by 500 micrograms.kg 1.min-1 continuous infusion) in WKY rats (n = 8) resulted in a significant increase in mean arterial pressure (MAP, 122 +/- 3 to 152 +/- 2 mmHg), RIHP (4.7 +/- 0.4 to 6.7 +/- 0.5 mmHg), fractional excretion of sodium (FENa, 0.76 +/- 0.21 to 4.74 +/- 0.70%), and urine flow rate (V, 27.7 +/- 5.0 to 161.3 +/- 19.6 microliters/min). Increases in RIHP and sodium and water excretions are abolished when renal perfusion pressure is prevented from increasing with L-NMMA infusion in a group of WKY rats (n = 6). In SHR (n = 6) administration of the same dose of L-NMMA resulted in no significant changes in MAP (172 +/- 3 to 178 +/- 2 mmHg) or RIHP (3.3 +/- 0.4 to 3.5 +/- 0.6 mmHg), but significantly higher increases in FENa (1.19 +/- 0.26 to 7.52 +/- 0.68%) and V (47.1 +/- 10.0 to 248.3 +/- 25.7 microliters/min) compared with WKY rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203561 TI - Role of intracellular Ca2+ in modulation of tight junction resistance in A6 cells. AB - The role of intracellular Ca2+ in the development and maintenance of epithelial tight junctional integrity is poorly understood. We assessed tight junctional resistance (Rj) in confluent monolayers of A6 cells that were treated with mucosal amiloride such that the transepithelial resistance (Rt) reflects Rj. Solution Ca2+ concentration [Ca2+] was reduced by ethylene glycol-bis(beta aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) addition to the bathing solutions. Reduction of mucosal [Ca2+] to 1 microM or reduction of serosal Ca2+ to 100 microM did not significantly alter Rt. However, a further decrease of serosal Ca2+ to 40 microM caused the resistance to fall to < 12% of the control value. Following restoration of serosal [Ca2+], Rt increased to a new steady state value within approximately 15 min. The magnitude of recovery of Rt was inversely correlated with the length of time the epithelium was exposed to low serosal [Ca2+]. To further test the effects of asymmetric Ca2+ removal, the serosal [Ca2+] was chelated using EGTA to reduce Rt. When the Ca2+ ionophore A 23187 was subsequently added to the mucosal solution, Rt increased from 20% to 60% of the control level. In addition, cells were loaded with the fluorescent Ca2+ indicator, Calcium Green, and the temporal relationship between changes in Rt and intracellular Ca2+ was determined. Following removal of serosal Ca2+, cell Ca2+ decreased, followed by a decrease in Rt. In contrast, returning Ca2+ to the serosal bathing solution resulted in a parallel increase of both Rt and cell [Ca2+]. These data strongly suggest that changes in intracellular [Ca2+] play an important role in the regulation of Rj. PMID- 8203562 TI - Inhibition of Na+/Ca2+ exchange in renal BLMV by IP3 depends on site of action and direction of Ca2+ flux. AB - It has previously been shown in synaptosomes that inositol 1,4,5-trisphosphate (1,4,5-IP3) inhibits Ca2+ transport by the plasma membrane-bound Na+/Ca2+ exchanger. The present study was therefore designed to determine if the effect of 1,4,5-IP3 was dependent on its site of action at the plasma membrane or on the direction of Ca2+ flux. To investigate this possibility, studies were performed in basolateral membrane vesicles (BLMV) isolated from rat renal cortex. As with synaptosomes, Ca2+ transport was inhibited by 1,4,5-IP3 in a concentration dependent manner. At a concentration of 10(-6) M, 1,4,5-IP3 significantly (P < 0.005) inhibited Ca2+ transport by 36%. When Ca2+ transport was carried out in inside-out vesicles, 10(-6) M 1,4,5-IP3 significantly (P < 0.002) increased the degree of inhibition by an additional 75% (63 vs. 36%). However, 1,4,5-IP3 had no significant effect on Ca2+ transport in inside-out vesicles when Ca2+ flux was reversed (i.e., Ca2+ efflux). These data in renal BLMV confirm the novel action of 1,4,5-IP3 on the Na+/Ca2+ exchanger previously described in brain synaptosomes. These results also suggest that the action of 1,4,5-IP3 depends on both its site of action at the plasma membrane and on the direction of Ca2+ flux. PMID- 8203563 TI - Adenosine A1 receptor-mediated inhibition of vasopressin action in inner medullary collecting duct. AB - We examined the effects of adenosine and adenosine analogues on arginine vasopressin (AVP)-induced increases in osmotic water permeability (Pf; micron/s) and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in rat inner medullary collecting ducts (IMCDs). When added to the bath, the A1 receptor agonist N6-cyclohexyladenosine (CHA) produced a rapid and reversible inhibition of AVP-stimulated (10 pM) Pf (1,781 +/- 195 to 314 +/- 85 microns/s at 0.3 microM CHA; n = 9). The inhibitory effect of CHA was concentration dependent, with a 50% inhibitory concentration of 10 nM. The effect of CHA was inhibited by prior exposure of IMCDs to the A1 receptor antagonist 1,3-dipropylxanthine-8 cyclopentylxanthine (DP-CPX; 1 microM) or by preincubation with pertussis toxin. CHA had no effect on cAMP-induced increases in Pf. In addition to CHA, adenosine and the nonselective agonist 5'-(N-ethylcarboxamido)-adenosine (NECA) inhibited AVP-dependent Pf by > or = 70%, whereas the A2 receptor agonist CGS-21680 had no effect. Luminal adenosine (0.1 mM) had no effect on basal or AVP-stimulated Pf. CHA, NECA, and adenosine but not CGS-21680 inhibited AVP-stimulated cAMP accumulation in a concentration-dependent manner (50% inhibitory concentrations 0.1-300 nM). The inhibitory effect of CHA on AVP-stimulated cAMP accumulation was attenuated by DPCPX. We conclude that adenosine, acting at the basolateral membrane, inhibits AVP action in the IMCD via interaction with A1 receptors. The inhibition occurs proximal to cAMP generation and likely involves an inhibitory G protein. PMID- 8203564 TI - Urate transport in brush-border membrane of human kidney. AB - Mechanisms of urate transport were investigated in human renal brush-border membrane vesicles. The imposition of an outwardly directed Cl- gradient, in voltage-clamp and pH-clamp conditions, stimulated [14C]urate uptake. Organic anions, including pyrazinoate (PZA), probenecid, lactate, ketone bodies, succinate, and alpha-ketoglutarate in their monovalent forms, cis-inhibited [14C]urate uptake. The affinity order was PZA > urate > probenecid > other anions. Vesicle preloading with these anions trans-stimulated urate uptake. These observations demonstrate the presence of a urate/anion exchanger. p Aminohippurate and OH- were not substrates for this exchanger. In the presence of an inwardly directed K+ gradient and valinomycin (intravesicular positive potential) [14C]urate uptake was stimulated. Voltage-sensitive [14C]urate uptake was cis-inhibited by organic anions in the following affinity order: urate > probenecid > PZA. The differences in affinity orders for the urate exchanger and the urate voltage-sensitive transport suggest different pathways for apical transport. The anion exchanger might be the main mechanism involved in urate tubular reabsorption in humans. PMID- 8203565 TI - Lithium reabsorption in perfused loops of Henle: effects of perfusion rate and bumetanide. AB - The contribution of the loop segments to lithium reabsorption in sodium-replete, anesthetized Sprague-Dawley rats was examined by perfusing superficial loops of Henle between late proximal convolutions and early distal tubules. Preliminary experiments in which lithium was initially present only inside or outside the perfused loop confirmed substantial permeability of one or more of the loop segments to lithium. In subsequent experiments, in which lithium was infused intravenously and included in the perfusate so that the perfusate-to-plasma lithium concentration ratio was close to that found in late proximal tubules during lithium clearance studies, lithium reabsorption was inversely related to the perfusion rate: values for fractional lithium reabsorption (FRLi) at perfusion rates of 10, 20, and 30 nl/min were 58 +/- 3, 17 +/- 2, and 2 +/- 2%, respectively. Bumetanide (10(-6) M) markedly inhibited FRLi but also reduced water reabsorption, suggesting an effect on the pars recta at this dose; 10(-7) M bumetanide, which was without effect on water reabsorption, had only a small effect on FRLi at a perfusion rate of 10 nl/min but reduced FRLi by approximately 70% at 20 nl/min. We argue that the remarkable flow dependency of lithium reabsorption, together with its bumetanide sensitivity, provides evidence for significant voltage-driven lithium reabsorption in the thick ascending limb of Henle. PMID- 8203566 TI - A novel approach allows identification of K channels in the lateral membrane of rat CCD. AB - We have developed a novel approach to study K channels in the lateral membrane of principal cells (PC) in rat cortical collecting ducts (CCD). The technique consists of 1) exposing the CCD apical membrane, 2) removing the intercalated cells adjoining a PC by gentle suction through a pipette, and 3) applying patch clamp technique to the lateral membrane of PC. Functional viability of the PC was confirmed by three indexes: 1) maintenance of physiological cell membrane potentials (-85 +/- 3 mV); 2) depolarization of the cell membrane potential with 1 mM Ba2+; and 3) hyperpolarization of the cell potential with 0.1 mM amiloride. Two types of K channels were identified: a low-conductance K channel and an intermediate-conductance K channel. In cell-attached patches the slope conductance of the low-conductance K channel was 27 pS and that of the intermediate-conductance K channel was 45 pS. The open probability (Po) of the 27 pS K channel was 0.81 +/- 0.02 and was not voltage dependent. In contrast, the Po of the 45-pS K channel was 0.23 +/- 0.01 at the spontaneous cell membrane potential and was increased by hyperpolarization. In addition, decrease of the bath pH from 7.4 to 6.7 reduced the 27-pS K channel current amplitude in a voltage-dependent manner, but the Po was not affected. Finally, two time constants were required to fit open- and closed-time histograms of both populations of K channels. Application of 1 mM Ba2+ completely blocked these K channels. We conclude that two types of K channel are present in the basolateral membrane of PC. PMID- 8203567 TI - Distinct cellular localization of mRNAs for three subtypes of prostaglandin E receptor in kidney. AB - Distribution of the mRNAs for three subtypes of prostaglandin E (PGE) receptors in the mouse kidney was investigated by in situ hybridization. The mRNA for EP1 subtype, which is coupled to Ca2+ mobilization, was specifically localized to the collecting ducts from the cortex to the papilla. The mRNA for EP2 subtype, which is linked to stimulation of adenylate cyclase, was localized to the glomeruli. The mRNA for EP3 subtype, which is coupled to inhibition of adenylate cyclase, was located densely in the tubules in the outer medulla and in the distal tubules in the cortex. These results exhibit distinct cellular localization of three subtypes of PGE receptor in the kidney and suggest that PGE2 exerts multiple functions via these subtypes expressed in different segments of the nephron. PMID- 8203568 TI - Regulation of ATP-sensitive K+ channels by ATP and nucleotide diphosphate in rabbit portal vein. AB - The modulation of ATP-sensitive K+ (KATP)-channel activity was investigated by recording single-channel currents in isolated smooth muscle cells from rabbit portal vein. K(+)-channel openers (KCOs; pinacidil, lemakalim, and nicorandil) induced burstlike openings of single KATP channels in the cell-attached configuration. After patch excision, KATP channels showed "run-down" phenomenon in the presence of KCOs, but subsequent application of Mg-ATP (1 mM) restored KATP-channel activity. Removal of Mg-ATP resulted in transient augmentation of KATP currents, which eventually decayed out. Nucleotide diphosphates (NDPs; GDP, ADP, UDP, IDP, and CDP) also induced channel reopening in the presence of KCOs, which was markedly enhanced by addition of Mg2+ in millimolar concentrations at the internal side of the membrane. The dose-response relation between ATP and the UDP-induced KATP-channel activity was shifted to the right in the presence of Mg2+ (2 mM). These results suggest that intracellular ATP, NDPs, and Mg2+ regulate the channel state of KATP channels (operative and inoperative states) and that KCOs open KATP channels only in the operative state. PMID- 8203569 TI - Myocardial relaxant effect of exogenous nitric oxide in isolated ejecting hearts. AB - In isolated myocytes and papillary muscles, both nitric oxide, acting through guanosine 3',5'-cyclic monophosphate (cGMP), and cGMP analogues exert a novel effect on myocardial contraction, influencing mainly the onset of relaxation. We studied the effect of the exogenous nitric oxide donor, sodium nitroprusside (0.1 10 microM), in isolated ejecting guinea pig hearts at constant filling pressure, afterload, and heart rate to identify its direct myocardial effects in the whole heart. Sodium nitroprusside induced concentration-dependent increases in coronary flow as well as premature and faster early left ventricular (LV) pressure decline, but did not change end-diastolic or peak LV pressure or peak rate of rise of LV pressure. There was no correlation between changes in coronary flow and LV pressure decline. Sodium nitroprusside effects were inhibited by hemoglobin, which inactivates nitric oxide. The cGMP-independent vasodilator nicardipine also increased coronary flow but did not influence early LV pressure fall. Thus exogenous nitric oxide exerts novel direct myocardial relaxant effects in the isolated ejecting heart, independent of its known vasodilator activity, and without compromising systolic function. PMID- 8203570 TI - Interaction of human platelets and leukocytes in modulation of vascular tone. AB - We tested the hypothesis that the vasodilator response to human platelets is modulated by polymorphonuclear leukocytes (PMNs). Responses to platelets activated with thrombin, as well as PMNs activated with N-formylmethionyl-leucyl phenylalanine (FMLP), were examined in perfused rabbit carotid arteries in vitro. Activation of platelets produced marked dilatation, and activation of PMNs produced modest constriction in arteries preconstricted with phenylephrine. Vasodilator responses to platelets were greatly impaired during infusion of activated PMNs. Pretreatment of PMNs with superoxide dismutase (SOD) partially restored dilator responses to platelets. Because SOD only partially restored vasodilator responses to platelets, we tested the possibility that adenosine diphosphatase (ADPase) activity of PMNs may degrade ADP released by platelets and thus reduce vasodilator responses. After incubation with PMNs, dilator responses to ADP, but not acetylcholine, were significantly impaired. These findings indicate that vasodilatation produced by activated human platelets is profoundly impaired by activated leukocytes. We conclude that two mechanisms may account for this effect: 1) endothelium-derived relaxing factor, released in response to platelet-derived ADP, is inactivated by superoxide anion generated by activated PMNs and 2) ADP is degraded by ADPase activity of PMNs. We speculate that platelet-leukocyte interaction may have important effects on vasomotor tone. PMID- 8203571 TI - Glibenclamide decelerates the responses of coronary regulation in the goat. AB - The role of blocking ATP-sensitive potassium (KATP) channels by glibenclamide on the dynamic responses of coronary resistance to abrupt changes in perfusion pressure and heart rate was investigated. The left main coronary artery of the open-chest anesthetized goat was perfused with constant pressure (Pp). Pp and arterial flow were averaged per beat, and their ratio was calculated as index of coronary resistance. Responses of resistance index after heart rate (HR) and Pp changes before and after administration of glibenclamide were compared. Their rate of change was quantified by t50, the required time to obtain half of the complete response. During control, t50 for the dilating response induced by a decrease in Pp or increase in HR was 3.8 +/- 0.2 and 6.2 +/- 0.5 (SE) s, respectively. With glibenclamide these values were 24.4 +/- 1.6 and 14.9 +/- 2.1 s. For the constricting response, the numbers for control were 5.8 +/- 0.3 (increase Pp) and 7.2 +/- 0.8 (decrease HR) s. With glibenclamide these values were 22.1 +/- 1.5 and 16.0 +/- 2.9 s. The steady-state adjustment of coronary flow was not altered by glibenclamide. It was concluded that glibenclamide has a minor effect on coronary flow control but reduces the rate of change of coronary resistance index up to a factor of four. Because glibenclamide is supposed to act on KATP channels, it may be concluded that these channels play a major role in the dynamics of coronary blood flow regulation. PMID- 8203572 TI - GABAB receptor-mediated mechanisms in the RVLM studied by microinjections of two GABAB receptor antagonists. AB - The cardiovascular effects of microinjections of two gamma-aminobutyric acid (GABA) antagonists specifically acting on GABAB receptors, 2-hydroxy-saclofen (2 OH-S) and CGP-35348, into vasopressor sites of rostral ventrolateral medulla (RVLM) were studied in rats anesthetized with urethan. Bilateral microinjection of 2-OH-S induced significant increases in mean arterial pressure (MAP) and heart rate (HR) in 21 of 26 RVLM vasopressor sites (81%); average increases obtained in the 26 sites studied were +25.2 +/- 3.0 mmHg and +12.7 +/- 2.1 beats/min. Bilateral microinjection of CGP-35348 induced significant increases in MAP and HR in 10 of 12 RVLM sites (83%). Average increases in the 12 sites studied were +27.6 +/- 3.9 mmHg and +14.6 +/- 2.5 beats/min. Sixteen rats received unilateral electrolytic lesions of one RVLM. Microinjections of either 2-OH-S or CGP-35348 into vasopressor sites within the intact RVLM significantly antagonized the depressor responses observed after injections of baclofen (20 pmol) into the same sites, whereas both GABAB antagonists did not affect the depressor response induced by microinjection of muscimol (5 pmol). These results suggest a tonic inhibitory mechanism within the RVLM mediated by GABAB receptors involved in central cardiovascular regulation. PMID- 8203573 TI - Inhibition of the calcium paradox in isolated rat hearts by high perfusate sucrose concentrations. AB - If a colloid osmotic (oncotic) pressure gradient develops across the myocyte membrane during the calcium paradox, adding an oncotic agent to the perfusate should be inhibitory. After 10-min perfusion with Ca(2+)-free Krebs-Henseleit (KH) buffer under constant flow at 34 degrees C, myoglobin release was measured from Langendorff hearts reperfused with Ca(2+)-containing KH buffer. When the Ca(2+)-free medium contained 200 mM sucrose, myoglobin release was reduced to 5% of that observed in the absence of sucrose, a change that was not seen when 200 mosM NaCl, choline chloride, LiCl, or glycerol was added. Replacement of 75 mM NaCl in the perfusate with 150 mM sucrose resulted in myoglobin release values that were 4% of the control. Plots of myoglobin release against sucrose concentration under these hypertonic and isotonic conditions yielded similar though separate curves. Sucrose also inhibited increases in wet weight-to-dry weight ratio and decreases in ATP and phosphocreatine contents. These results support the hypothesis that an oncotic pressure gradient arises during the calcium paradox at the moment of increased membrane permeability and plays a major role in its development. PMID- 8203574 TI - Effects of myocardial hypertrophy on transient outward current. AB - In the one-clip, two-kidney model of hypertensive rat, a gradual chronic pressure overload is imposed on the heart. Myocardial hypertrophy resulting from such pressure overload is associated with an increased but slower inactivating L-type calcium current and prolongation of action potential duration. Voltage clamp experiments in a variety of excitable tissues indicate that a 4-aminopyridine sensitive transient outward current (Ito) plays an important role in regulating the action potential duration. Accordingly, we studied Ito in single adult cardiac myocytes enzymatically isolated from hypertrophied left ventricles of the renovascular hypertensive (HBP) rat hearts using the whole cell patch-clamp method. The current densities (normalized to cell capacitative surface area) measured at the early transient peak Ito, at the steady state, and as the difference between the transient peak and the steady state were larger in HBP cells (n = 23) than in control (Ctrl) cells (n = 20) (P < 0.05). There was no difference in the Ito reversal potential between Ctrl (-60.9 +/- 1.9 mV, mean +/- SE; n = 16) and HBP (-63.7 +/- 2.6 mV; n = 19) cells. The observed increase in Ito amplitude was not due to an increase in the number of channels available for activation or in the fraction of channels activated because there were no statistical differences in the membrane potential at which one-half of the Ito channels are activated (V0.5) for the steady-state activation and inactivation curves between Ctrl and HBP cells. The time course of inactivation of Ito was described by a double-exponential function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203575 TI - Protective effects of N-acetyl-L-cysteine in endotoxemia. AB - Because oxygen free radicals have been implicated in the endothelial cell damage and in the myocardial depression occurring during severe sepsis, we investigated whether N-acetyl-L-cysteine (NAC) could influence the oxygen extraction capabilities during an acute reduction in blood flow induced by cardiac tamponade after endotoxin challenge. Sixteen anesthetized, saline-infused, and ventilated dogs received Escherichia coli endotoxin (2 mg/kg) 30 min before tamponade was induced by repeated bolus injections of warm saline into the pericardial space. Thirty minutes before endotoxin administration, nine dogs received NAC (150 mg/kg, followed by a 20 mg.kg-1.h-1 infusion); the other seven dogs served as a control group. The NAC group maintained higher cardiac index, oxygen delivery (DO2), and left ventricular stroke work index, but lower systemic and pulmonary vascular resistance, than the control group. The oxygen uptake (VO2) levels at critical DO2 (DO2crit) were identical in the two groups. However, DO2crit was significantly lower in the NAC than in the control group (8.1 +/- 1.7 vs. 10.8 +/ 1.8 ml.kg-1.min-1, P < 0.01). Critical oxygen extraction ratio and the slope of the VO2-to-DO2-dependent line were higher in the NAC than in the control group (72 +/- 14 vs. 53 +/- 15% and 0.80 vs. 0.56, respectively; both P < 0.05). The peak lactate and the maximal tumor necrosis factor (TNF) levels were lower in the NAC than in the control group (5.2 +/- 0.4 vs. 7.6 +/- 0.4 mM, and 0.14 +/- 0.03 vs. 1.21 +/- 0.58 ng/ml, respectively; both P < 0.01). NAC significantly increased glutathione peroxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203576 TI - Cerebrovascular responsiveness to CO2 in Haemophilus influenzae type b meningitis in rabbits. AB - The effect of experimental meningitis on regional cerebral blood flow (rCBF), cerebral metabolic rate for oxygen (CMRO2), and cerebrovascular responsiveness to CO2 was determined in pentobarbital-anesthetized rabbits. The animals were inoculated intracisternally with saline (control) or log-phase Haemophilus influenzae type b (Hib). Eighteen hours later rCBF was determined with radiolabeled microspheres at normocapnia, hypocapnia, and hypercapnia. Cerebrovascular responses to hypocapnia and hypercapnia were assessed by calculating the change in cerebrovascular resistance per millimeter mercury change in PaCO2. At all CO2 levels, meningitis (M) was associated with elevated CBF compared with control (C: 47.5 +/- 3.0, M: 60.9 +/- 4.5 ml.100 g-1.min-1 at normocapnia, P < 0.01). Regional differences were present. In forebrain, the hyperemia in meningitis was confined to the superficial cortical grey matter. When compared with control, meningitis was not associated with altered vasoreactivity during hypocapnia (C: -0.026 +/- 0.006, M: -0.026 +/- 0.008 mmHg.ml-1 x 100 g-1.min-1.mmHg PaCO2(-1)) or hypercapnia (C: -0.037 +/- 0.004, M: -0.026 +/- 0.008 mmHg.ml-1 x 100 g.min.mmHg PaCO2(-1)). CMRO2 in meningitis was not significantly different from control (C: 3.53 +/- 0.29, M: 3.51 +/- 0.22 ml O2.100 g-1.min-1). These findings indicate that cerebrovascular responsiveness to CO2 is preserved in experimental Hib meningitis. Furthermore, enhanced CBF together with unchanged CMRO2 indicates that "luxury" cerebral perfusion is present in this model of bacterial meningitis. PMID- 8203577 TI - Pressure sensitivity of flow oscillations in postocclusive reactive skin hyperemia. AB - Skin blood flow was monitored using a laser-Doppler (LD) flowmeter in 21 healthy volunteers after an occlusion of the digital arteries. The peripheral vascular bed was exposed to occlusion ischemia of varying duration (1, 4, or 8 min) and to a change in digital arterial pressure produced by different positions of the arm above heart level to characterize the pattern of LD flow oscillations in postocclusive reactive hyperemia (PRH) and to elucidate the relevance of metabolic and myogenic mechanisms in governing its fundamental frequency. The descending part of the hyperemic flow was characterized by the appearance of conspicuous periodic oscillations with a mean fundamental frequency of 7.2 +/- 1.5 cycles/min (SD, n = 9), as assessed by a Fourier transform frequency analysis of 50-s sections of flow. The mean respiratory frequency during the periods of flow frequency analysis was 17.0 +/- 2.2 (SD, n = 9), and the PRH oscillations remained during apnea in all tested subjects. The area under the maximum flow curve increased significantly with prolongation of the occlusion (paired t test, P < 0.001; n = 9), but showed no dependence on the estimated blood pressure in the digital arteries, which suggests the predominant role of a metabolic component in this part of the PRH response. In contrast, the fundamental frequency of PRH oscillations exhibited a significant decrease with a reduction in the estimated digital arterial pressure (linear regression, b = 0.08, P < 0.001; n = 12), but did not change with the prolongation of arterial occlusion despite a significant increase in mean LD flow (paired t test, P < 0.001; n = 9).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203578 TI - beta-Adrenergic mechanisms attenuated hypoxic pulmonary vasoconstriction during systemic hypoxia in cats. AB - In this study, we examined how locally mediated hypoxic pulmonary vasoconstriction is modulated by autonomic nervous system activation during global alveolar hypoxia (GAH) accompanied by systemic hypoxemia. Using an X-ray television system on the in vivo cat lung, we measured changes in the internal diameter (ID) during GAH and regional alveolar hypoxia (RAH) without systemic hypoxemia in identical small pulmonary arteries and veins (100-600 microns ID). We also analyzed the effects of the autonomic nervous system blockade on the hypoxic ID changes. During GAH the ID of the arteries reduced by 5 +/- 1 and 3 +/ 1% with 10 and 5% O2 inhalations, respectively, whereas during RAH the arterial ID reduced by 12 +/- 1 and 18 +/- 1% with 10 and 5% O2 inhalations, respectively. The magnitude of the ID reduction was significantly smaller during GAH than during RAH. After pretreatment with propranolol, however, GAH induced large ID reductions (16 +/- 1 and 23 +/- 1% with 10 and 5% O2 inhalations) with patterns very similar to those seen during RAH. Phentolamine and atropine had no effect on the response during GAH. The ID reductions during RAH, on the other hand, were unaffected by all the blockers. The results indicate that, in the cat, alveolar hypoxia per se acts locally to constrict the small pulmonary vessels and that the hypoxic vasoconstriction is attenuated by a beta-receptor-mediated vasodilator effect during GAH with systemic hypoxemia. In addition, we found that, after adrenalectomy plus ganglion blockade with hexamethonium bromide, the GAH-induced ID reduction with 5% O2 inhalation was enhanced from 3 to 19%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203579 TI - EDRF suppresses chaotic pressure oscillations in isolated resistance artery without influencing intrinsic complexity. AB - It is now widely recognized that nonlinear oscillatory systems can exhibit simple periodicity, characteristic repetitive patterns of odd and even integral periodicity and specific pathways for the transition to irregular, so-called "chaotic," dynamics. In the present study we have identified such behavior in the highly irregular rhythmic vasomotor activity induced by histamine in isolated rabbit ear resistance arteries, thus suggesting a deterministic rather than random etiology. In this experimental model nonlinearity arises at the level of the vascular smooth muscle cell, since oscillatory behavior was not abolished by endothelial denudation. To quantify the complexity of the responses induced by histamine, we applied the analysis of Grassberger and Proccacia (Physica D 9: 189 208, 1983) to calculate a scaling parameter known as fractal dimension, which estimates the minimum number of control variables participating in the genesis of an irregular time-varying signal. The findings suggest the involvement of at least three such variables, because its average numerical value was generally found to be between 2 and 3. Neither the absolute concentration of histamine employed nor pharmacological manipulation (i.e., stimulation/inhibition) of endothelium-derived relaxing factor (EDRF) activity significantly affected the fractal dimension of the pressure fluctuations, although both influenced their superficial form. Histamine and EDRF consequently do not determine the fundamental interactions responsible for generating the chaotic nature of the responses and may be regarded as permissive and modulatory influences, respectively. The well-known unpredictability of nonlinear systems to perturbation may explain why EDRF can either suppress or enhance rhythmic vasomotor activity in different artery types. PMID- 8203580 TI - Acetylcholine-sensitive muscarinic K+ channels in mammalian ventricular myocytes. AB - Acetylcholine (ACh) is known to increase K+ conductance in the atrium and in pacemaker tissues in the heart. This effect has not been well defined in mammalian ventricular tissues. We have identified and characterized the ACh sensitive muscarinic K+ channel [IK(ACh)] activity in isolated human, cat, and guinea pig ventricular myocytes using the patch-clamp technique. Application of ACh increased whole cell membrane current in human ventricular myocytes. Current voltage relationship of the ACh-induced current in ventricle exhibited inward rectification whose slope conductance was smaller than that in atrium. In single channel recording from cell-attached patches, IK(ACh) activity was observed when ACh was included in the solution. The channel exhibited a slope conductance of 43 +/- 2 pS. Open times were distributed according to a single exponential function with mean open lifetime of 1.8 +/- 0.3 ms. The channel had conductance and kinetic characteristics similar to human atrial IK(ACh), which had a slope conductance of 43 +/- 3 pS and mean open lifetime of 1.6 +/- 0.3 ms. However, concentration of ACh at half-maximal stimulation (KD) of the channel in ventricle was greater (KD = 0.13 microM) than that in atrium (KD = 0.03 microM). Adenosine caused activation of the same K+ channel. After formation of an excised inside out patch, channel activity disappeared. Application of GTP (100 microM) or GTP gamma S (100 microM) to the solution caused reactivation of the channel. When myocytes were preincubated with pertussis toxin (PTX), ACh failed to activate these channels, indicating that the PTX-sensitive G protein, Gi, is essential for activation of IK(ACh). IK(ACh) channel activity was also found in cat and guinea pig ventricular myocytes. We conclude that ACh directly activates the IK(ACh) in mammalian ventricular myocytes via Gi in a fashion almost identical to atrial myocytes. PMID- 8203581 TI - Fluctuations in microvascular blood flow parameters caused by hemodynamic mechanisms. AB - We have developed a mathematical model of microvascular network blood flow in which the nonlinear flow properties of blood and the nonuniform axial distribution of red blood cells in each vessel, as well as disproportionate cell partitioning at bifurcations, are all accounted for. The movements of red blood cells in the network are tracked; hence, the model is able to simulate temporal variations in local flow parameters in the network due to hemodynamic mechanisms. The model was applied to four rat mesenteric networks for which the topology, boundary conditions, blood velocity, and discharge hematocrit (Hctd) had been measured for each branch. Temporal variations in Hctd and blood velocity after simulation convergence were predicted. In some cases of the three vessels connected to a node, Hctd of one vessel fluctuates in a simple periodic form, Hctd of the second one oscillates in a more complex periodic form, whereas the Hctd of the third one does not oscillate at all. These variations were obtained with constant flow boundary conditions and, therefore, are due to hemodynamic factors alone. The temporal variations in flow parameters predicted by the model simulations are caused by hemorheological mechanisms and would be superimposed on variations caused by other mechanisms (e.g., vasomotion). The frequencies of the predicted fluctuations in blood velocity are in qualitative agreement with observed in vivo variations in dual-slit velocity in the arterioles of the cremaster muscle of anesthetized Golden hamster. PMID- 8203582 TI - Effects of thapsigargin in normal and pretreated with ryanodine guinea pig cardiomyocytes. AB - We compared the effects of thapsigargin (TG), a selective blocker of Ca(2+) adenosinetriphosphatase of sarcoplasmic reticulum (SR), and ryanodine (Ry) in the single isolated myocytes of guinea pig ventricular myocardium loaded with indo 1 acetoxymethyl ester (AM). TG (2 x 10(-7) M) inhibited the rapid phase of Ca2+ transient, increased time to peak intracellular Ca2+ concentration ([Ca2+]i) from 158 +/- 12 to 391 +/- 60 ms and decreased the total amplitude of the transient to 89 +/- 4% of the pre-TG control. Time to peak of contractions increased from 350 +/- 47 to 410 +/- 37 ms and total duration from 666 +/- 62 to 850 +/- 198 ms. Total amplitude of contractions was hardly affected. In the cells not loaded with indo 1-AM TG decreased the amplitude of contractions to 71 +/- 3% of control. When the effects of TG were fully developed, the cells ceased to respond to 1 s of superfusion with 15.0 mM caffeine with transient elevation of [Ca2+]i and/or transient contracture. TG did not affect the amplitude or time course of Ca2+ current (ICa) or the current-voltage relation. We propose that Ca2+ transients and contractions in the cells treated with TG were initiated by sarcolemmal Ca2+ influx. Ry (1.0 microM) initiated similar changes in the time course of Ca2+ transients and contractions as TG; however, total amplitude of the transients and contractions was reduced to 78 +/- 5 and 55 +/- 7% of the control, respectively. The SR Ca2+ was also depleted by Ry. TG superfused over the cells pretreated with Ry increased the amplitude of Ca2+ transients and respective contractions to the pre-Ry level. TG did not affect the ICa in the cells pretreated with Ry nor did it change configuration of action potentials to increase the Ca2+ influx. We propose that the effect of Ry on amplitude of Ca2+ transients and contractions results from the trapping of a fraction of sarcolemmal Ca2+ influx by the SR and its rapid release into subsarcolemmal space. From there it is extruded out of the cell by Na(+)-Ca2+ exchange before ever reaching the contractile system. PMID- 8203583 TI - Pressurization of isolated renal arteries increases inositol trisphosphate and diacylglycerol. AB - Inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DAG) concentrations were measured in isolated, cannulated dog renal arteries under control conditions (0 mmHg) and in response to step elevations in transmural pressure. There was a pressure-dependent increase in IP3 at 60 and 120 mmHg, reaching significance at 120 mmHg (P < 0.05) and a significant increase in DAG at both 60 and 120 mmHg measured after maintaining pressure for 15 min. Similarly, IP3 measurements made 90 s after a step increase in transmural pressure also exhibited a pressure dependent profile, again reaching significance at 120 mmHg. Calculation of active tension demonstrated these renal arteries developed pressure-dependent myogenic tone. To assess the role of the endothelium in this regard, IP3 was measured before and after endothelial removal at 0 and 60 mmHg. Pressure-dependent myogenic tone was still present upon endothelial removal. In the absence of the endothelium, we observed a significant increase in total IP3 at 60 compared with 0 mmHg; furthermore, the increase in IP3 in the absence of the endothelium was significantly greater than that observed when the endothelium was intact. Given that the primary source of IP3 is via the actions of phospholipase C (PLC) on phosphatidylinositol 4,5-bisphosphate, these biochemical data directly demonstrate that elevation of transmural pressure in dog renal arteries activates PLC. PMID- 8203584 TI - Calcium is involved in both positive and negative modulation of the secretory system for ANP. AB - The calcium dependence of the atrial natriuretic peptide (ANP) secretory system is controversial. Some studies clearly support a stimulatory role, whereas others favor an inhibitory role for calcium in this endocrine system. We demonstrate that calcium is involved in both a positive modulatory role and a negative modulatory role, thereby providing some explanation for the seemingly irreconcilable findings previously published. The negative modulatory role performed by calcium is evident during basal secretion, whereas the positive modulatory role is especially evident in the sustained phase of the secretory response to stimulation. Furthermore, we demonstrate the calcium dependence of processing of the prohormone to the mature circulating form in a cell culture system. This supports the concept that processing is a function of the atrial myocyte rather than of the mesenchymal cells of the atrium. We have demonstrated previously that calcium is important for packaging of the prohormone into secretory granules. Together these findings support a multifaceted role for calcium in the regulation of the secretory apparatus for ANP. PMID- 8203585 TI - Angiotensin II enhances norepinephrine spillover during sympathetic activation in conscious rabbits. AB - To investigate the potential modulating influence of angiotensin II (ANG II) on sympathetic activity in response to changes in baroreflex activity, renal and total norepinephrine (NE) spillover rates were examined during sodium nitroprusside (SNP) and phenylephrine (PE) infusions in four groups of conscious rabbits: 1) saline (control); 2) subpressor ANG II (ANG II, 2 ng.kg-1.min-1); 3) enalaprilat (MK-422, 200 micrograms/kg and 3.3 micrograms.kg-1.min-1); and 4) MK plus ANG II (MK+ANG II). Upper plateaus of baroreflex-NE spillover curves for renal and total NE spillover were reduced in the MK group (25 and 81 ng/min) compared with control (38 and 125 ng/min) and MK+ANG II (37 and 155 ng/min). To investigate the interaction of ANG II and sympathetic activity during treadmill exercise, hindlimb NE spillover rate was examined in three groups of rabbits: 1) control, 2) MK, and 3) MK+ANG II. Exercise at 6 and 12 m/min produced similar effort-related hemodynamic responses in the three groups. At maximal exercise, hindlimb NE spillover was reduced in the MK group (29 +/- 3 ng/min) compared with control (62 +/- 17 ng/min, P < 0.05) and MK+ANG II group (51 +/- 10 ng/min). It is concluded that endogenous ANG II enhances sympathetic activity during pharmacological (baroreflex) and physiological stimulation. PMID- 8203586 TI - Heart rate variability in two models of cardiac hypertrophy in rats in relation to the new molecular phenotype. AB - The analysis of heart rate variability (HRV) provides information on neural control of the heart. We investigated HRV in normal rats and in models of experimental cardiac hypertrophy using the Holter monitoring and peak/trough method. In normal rats, two heart rate oscillations with different wavelengths, high frequency (HF) and low frequency (LF) oscillations, were detected. The HF oscillations were insensitive to propranolol and suppressed by atropine. The LF oscillations were sensitive to both antagonists. Thyrotoxicosis resulted in cardiac hypertrophy (+20%) and tachycardia. The HF oscillations were unchanged, whereas LF oscillations were hampered at low heart rate in this group. Aortic stenosis resulted in cardiac hypertrophy (+53%), but heart rate oscillations were unchanged. The (number x amplitude) product for both types of oscillations correlated with heart rate in controls but not in the thyrotoxicosis or aortic stenosis models. Alterations of HRV in cardiac hypertrophy occur in rats as in humans. They may reflect the changes in the molecular components of the adrenergic/muscarinic system, which defines the new myocardial phenotype. PMID- 8203587 TI - Cytochrome P-450 inhibitors alter afferent arteriolar responses to elevations in pressure. AB - The present study evaluated the effects of cytochrome P-450 inhibitors on the response of the renal microvasculature to changes in renal perfusion pressure and on autoregulation of glomerular capillary pressure using the rat juxtamedullary nephron microvascular preparation perfused in vitro with a cell-free perfusate containing 5% albumin. The basal diameters of the proximal and distal afferent arterioles averaged 28 +/- 1 (n = 32) and 18 +/- 1 micron (n = 23), respectively, at a control perfusion pressure of 80 mmHg. The diameters of these vessels decreased by 8% when perfusion pressure was elevated from 80 to 160 mmHg. After addition of cytochrome P-450 inhibitors (either 17-octadecynoic acid, 20 microM; 7-ethoxyresorufin, 10 microM; or miconazole, 20 microM) to the perfusate, the diameters of the proximal and distal afferent arterioles increased by 6% in response to the same elevation in perfusion pressure. Control glomerular capillary pressure averaged 43 +/- 1 mmHg (n = 32) at a renal perfusion pressure of 80 mmHg and increased by only 9 +/- 1 mmHg when perfusion pressure was elevated to 160 mmHg. Autoregulation of glomerular capillary pressure was impaired after addition of the cytochrome P-450 inhibitors, and it increased by 18 +/- 2 mmHg when perfusion pressure was varied over the same range. These results indicate that cytochrome P-450 inhibitors attenuate the vasoconstrictor response of afferent arterioles to elevations in renal perfusion pressure and impair autoregulation of glomerular capillary pressure, suggesting a possible role for cytochrome P-450 metabolites of arachidonic acid in these responses. PMID- 8203588 TI - Characteristics of myocytes isolated from hearts of renovascular hypertensive guinea pigs. AB - A model of renovascular hypertension has been developed in the guinea pig using the Goldblatt (2-kidney, 1-clip) operation. Systolic and diastolic blood pressures were significantly increased 3 and 7 wk after the operation, but levels fell to control values at 11 wk. The two-dimensional areas of myocytes isolated from the hearts of Goldblatt-operated (GB) animals were larger than those in control cells at 3 wk (cf. 3,397 +/- 87 and 2,208 +/- 125 microns 2, P < 0.01), and the difference was maintained at 7 and 11 wk. No change in cell contraction or relaxation characteristics were seen at either 3 or 7 wk after clipping. Myocytes from the 11-wk GB group showed a significantly reduced contraction amplitude and velocity at 32 degrees C in maximally activating Ca2+ or isoproterenol concentrations (%cell shortening in Ca2+, cf. 6.8 +/- 0.4 and 10.0 +/- 0.9, P < 0.01). Concentrations eliciting 50% of maximal response for Ca2+ or isoproterenol were unchanged, as was the ratio of isoproterenol to Ca2+ effect in the same cell. Increases in time to peak contraction (TTP) and time to 50% relaxation (R50) were observed in 11-wk GB myocytes, but only at room temperature. There was no lengthening of TTP or R50 of the Ca2+ transient, nor was there any change in Ca2+ current density or inactivation kinetics in these myocytes. PMID- 8203589 TI - Endothelial actin cytoskeleton in rat mesentery microvasculature. AB - The actin cytoskeleton plays a key role in maintaining and modulating cellular morphology and thus is important in various aspects of endothelial cell function, yet few studies to date have studied the endothelial actin cytoskeleton in the microvasculature, where many of the specialized endothelial functions take place. We developed a method to fix and stain the microvasculature of the rat mesentery under physiological conditions and used a confocal microscope to observe the pattern of actin filaments in individual endothelial cells throughout the intact vascular network. We observed several distinct patterns of actin filaments in the endothelial cells depending on the caliber and type of vessel. The endothelial cells of large arterioles and venules (> 50 microns in diameter) displayed a prominent circumferential rim of actin, with few central actin fibers. Endothelium of midsized (20-50 microns) arterioles (and some midsized venules) displayed prominent abluminal actin fibers across the central portion of the cell, aligned parallel to the longitudinal axis of the vessel, in addition to a peripheral rim of actin. The endothelium of capillaries contained few actin fibers but instead typically displayed diffuse staining throughout the cell. The endothelial cells in the postcapillary venules generally displayed a thin peripheral rim of actin and occasional short central fibers. These results indicate that the local environment dictates the actin pattern in endothelial cells and suggests that specialized endothelial function is correlated with specialized endothelial actin architecture. PMID- 8203590 TI - Effects of intra-atrial injection of colored microspheres on systemic hemodynamics and regional blood flow in rats. AB - The hemodynamic effects of various numbers of colored nonradioactive microspheres (CMS) and those of accumulation of CMS caused by multiple sequential injection were evaluated in 51 Sprague-Dawley male rats. CMS (15 microns) were injected into the left atrium. Regional blood flow and cardiac output were evaluated using the reference blood sample technique. Ficoll-70 was given after each blood sample withdrawal as a fluid replacement. A bolus injection of < or = 1,000,000 CMS caused no significant hemodynamic disturbances. Amounts of 500,000 CMS can be repeatedly injected up to four times (cumulative dose of 2,000,000 CMS) without producing any adverse hemodynamic effects. The values of cardiac output obtained with the CMS technique were correlated well (r = 0.971, P < 0.0001) with those obtained with electromagnetic flow probes. An excellent reproducibility of organ blood flow was observed after four sequential injections of 500,000 CMS. This study establishes the limits of CMS that can be injected into the rat without inducing hemodynamic changes and also suggests that the CMS technique can be employed to evaluate cardiac output and regional blood flow precisely and repeatedly. PMID- 8203591 TI - Effect of chronic renal medullary nitric oxide inhibition on blood pressure. AB - The effects of chronic nitric oxide inhibition in the renal medulla on renal cortical and medullary blood flow, sodium balance, and blood pressure were evaluated in conscious uninephrectomized Sprague-Dawley rats. During a 5-day renal medullary interstitial infusion of the nitric oxide inhibitor NG-nitro-L arginine methyl ester (L-NAME, 120 micrograms/h) in saline (0.5 ml/min), renal medullary blood flow was selectively decreased by 30% after 2 h and was maintained at that level for the entire infusion. The decrease in medullary blood flow was associated with sodium retention and increased blood pressure. After the cessation of L-NAME infusion, medullary blood flow returned to control, and the sodium balance became negative as blood pressure returned to baseline. These data indicate that renal medullary nitric oxide plays an important role in the regulation of renal blood flow, sodium excretion, and blood pressure. PMID- 8203592 TI - Accelerated myocardial relaxation in conscious dogs during acute cardiac tamponade. AB - Eight chronically instrumented conscious dogs were used to test the hypothesis that left ventricular (LV) relaxation is accelerated during cardiac tamponade. The time constant of LV transmural pressure fall was measured before and during intrapericardial (IP) saline infusion (baseline) with and without beta-adrenergic blockade (propranolol 1 mg/kg iv). Heart rate was controlled by atrial pacing. Increasing IP pressure caused a progressive linear decrease in stroke volume before and during beta-blockade in each animal. The time constant of LV transmural pressure fall also decreased continuously with an increase in IP pressure from 26 +/- 7 ms during baseline to 18 +/- 5 ms during severe cardiac tamponade (P < 0.01) before beta-blockade. However, after beta-blockade, the time constant of LV transmural pressure fall was constant over a wide range of IP pressures despite a continuous decrease in LV end-diastolic volume. The time constant of LV transmural pressure fall was not altered by vena caval occlusions that caused the same decrease in LV preload observed during cardiac tamponade. We concluded that despite decreased pump function, LV relaxation was accelerated progressively during graded cardiac tamponade, and this change was dependent not on changes in loading conditions but on an intact beta-adrenergic influence. PMID- 8203593 TI - Vasomotor tone affects diastolic coronary flow and flow impediment by cardiac contraction similarly. AB - We studied the effect of cardiac contraction on coronary arterial flow with vasomotor tone (control) and during maximal vasodilation with adenosine in the isolated blood-perfused rat heart at constant perfusion pressure (105 mmHg) with a left ventricular balloon (n = 6). Ventricular pressure was changed by volume changes and contractility via postextrasystolic potentiation. Contractility was expressed as the slope of the end-systolic pressure-volume ratio, elastance. Constant vasomotor tone was judged from stable diastolic flow. Coronary flow reduction (diastolic minus systolic flow, delta CBF, ml.min-1.g-1) due to contraction was related to developed ventricular pressure (devPLV) and developed elastance (devELV, systolic minus diastolic elastance) by multiple regression: delta CBF = SP.devPLV+SE.devELV+I, where SP and SE represent changes in coronary blood flow due to changes in devPLV and devELV, respectively, and I is intercept. In control, delta CBF = (0.016 +/- 0.008).devPLV + (0.0022 +/- 0.0009).devELV + (0.29 +/- 0.77); during vasodilation, delta CBF = (0.046 +/- 0.011).devPLV + (0.009 +/- 0.0053).devELV + (2.50 +/- 2.56). Diastolic flow increased by a factor of 4.06 +/- 1.57 (SD) during vasodilation. The increases in diastolic flow, SP, and SE were not different. We conclude that vasodilation has similar effects on diastolic flow and flow amplitude without affecting the relative contributions of ventricular pressure and contractility. PMID- 8203594 TI - Coupling of M-cholinoceptors and A1 adenosine receptors in human myocardium. AB - This study investigated the coupling of M-cholinoceptors and A1 adenosine receptors in human myocardium. Carbachol reduced force of contraction in atria and ventricles by 60 and 35% (in the presence of 0.03 microM isoprenaline), respectively. Addition of (-)-N6-(2-phenylisopropyl)adenosine (R-PIA) in the presence of carbachol did not further reduce force of contraction. R-PIA reduced force of contraction less than carbachol in atria (ventricles) by 35% (25%), but addition of carbachol after R-PIA reduced force of contraction further by 35% (15%). Carbachol increased 35S-labeled guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) binding maximally 14-fold only when GDP was present by an excess of > 100 times [35S]GTP gamma S, while R-PIA increased binding only 2-fold. Activation of [35S]GTP gamma S binding by A1 adenosine receptor and M-cholinoceptor stimulation was antagonized by theophylline and atropine, respectively. Addition of R-PIA to carbachol did not further increase [35S]GTP gamma S binding. Activation of high-affinity [35S]GTP gamma S binding by agonists showed that carbachol activated [35S]GTP gamma S binding to 20 pmol/mg protein [35S]GTP gamma S binding sites, i.e., 25% of the total number of binding sites (80 pmol/mg protein). With R-PIA, activation of high-affinity [35S]GTP gamma S binding could not reliably be detected with this technique. From the number of M-cholinoceptors (atria, 360 fmol/mg protein; ventricle, 270 fmol/mg protein), it is estimated that 1 M-cholinoceptor activates approximately 50-80 G protein alpha-subunits in atria and ventricles, respectively. It is concluded that stimulation of M cholinoceptors but not A1 adenosine receptors is able to maximally activate a pool of G protein alpha-subunits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203596 TI - Release of atrial natriuretic peptide in brief ischemia-reperfusion in isolated rat hearts. AB - We studied the effects of short-term global ischemia and reperfusion on ANP secretion from Langendorff-perfused rat hearts compared with isolated ventricles. Effects of regional ischemia, with or without increased atrial pressure, were examined in Langendorff-perfused and working heart models. Five minutes of global ischemia were associated with elevated levels of atrial natriuretic peptide (ANP) in the coronary effluent immediately and for approximately 10 min after resumption of reperfusion, resulting in a net hormone excess of 23 +/- 5 ng/g wet wt. The ventricles produced on the average 11% ANP compared with the whole heart, and their contribution of to postischemic ANP overflow was approximately proportional to their basal production. In Langendorff-perfused hearts, regional ischemia increased the concentration of ANP in the coronary effluent 51 +/- 11%, whereas the secretion rate (per minute) decreased 18 +/- 5%. In the presence of atrial distension in the working heart model, a trend for increase in ANP secretion was apparent. We conclude that global ischemia, even of brief duration, has an independent stimulatory effect on ANP release, the ischemic atrium being responsible for most of the excess. Regional ischemia, when not accompanied by atrial distention, reduces the ANP secretion rate during the ischemic period. Heart failure secondary to ischemia stimulates ANP secretion, but this response seems to be both delayed and attenuated compared with atrial stretch alone. PMID- 8203595 TI - High-energy phosphate responses to tachycardia and inotropic stimulation in left ventricular hypertrophy. AB - Spatially localized nuclear magnetic resonance (NMR) spectroscopy was used to examine the effect of tachycardia and inotropic stimulation on myocardial ATP, creatine phosphate (CrP), and inorganic phosphate (Pi) in animals with left ventricular hypertrophy (LVH). Studies were performed in eight normal dogs and seven dogs with moderate LVH produced by banding the ascending aorta. 31P-NMR spectra were obtained from five layers across the LV wall, while blood flow (BF) was measured with microspheres during control conditions, pacing at 200 and 240 beats/min, and during dobutamine infusion (Dob). Myocardial ATP and CrP levels were normal in the LVH hearts during control conditions. Pacing did not alter the transmural distribution of perfusion or the levels of CrP, ATP, and Pi in normal hearts. In contrast, in four of seven LVH hearts, pacing decreased the subendocardial/subepicardial (ENDO/EPI) BF ratio and caused depletion of CrP and appearance of Pi characteristic of ischemia in the subendocardium. Dob produced greater increases in the heart rate x LV systolic pressure product (RPP) and greater increases of Pi and decreases of CrP in LVH than in normal hearts; however, at comparable elevations of RPP the alterations of Pi and CrP were similar in both groups. Although Dob decreased the ENDO/EPI in LVH hearts, Dob induced alterations in CrP and Pi were uniform across the LV wall. Increasing myocardial BF with adenosine or carbochromen did not reverse the alterations in Pi or CrP produced by Dob. We conclude that 1) ENDO perfusion abnormalities during tachycardia in LVH do produce ENDO subendocardial ischemia; 2) when the degree of augmentation of mechanical performance is considered, the metabolic changes induced by Dob were similar in normal and LVH hearts; 3) Dob-induced alterations in Pi and CrP were not related to inadequate perfusion, since increasing coronary BF did not reverse these changes; and 4) alterations of Pi and CrP during Dob infusion were not more prominent in the ENDO, indicating that the decreased ENDO/EPI flow did not cause ENDO ischemia but may reflect relatively lower O2 demands in this region during inotropic stimulation. PMID- 8203597 TI - Reflex control of active cutaneous vasodilation by skin temperature in humans. AB - The purpose of this study was to examine whether reflex effects of changes in whole body skin temperature (Tsk) on cutaneous vasculature are mediated through the vasoconstrictor or the active vasodilator arm of the sympathetic nervous system. In six subjects, reflex responses in forearm skin blood flow (SkBF) to changes in Tsk were monitored by laser-Doppler flowmetry. SkBF was monitored at a control site and at a 0.6-cm2 site where bretylium (BT) had been iontophoretically applied to abolish sympathetic vasoconstrictor control. Reflex control of SkBF at BT-treated sites is solely through active vasodilator activity. An index of cutaneous vascular conductance (CVC) was calculated from the blood flow signal and mean arterial pressure, measured noninvasively. Data are expressed relative to maximum CVC (CVCmax) achieved by local warming of measurement sites to 42 degrees C at the end of each study. Tsk was controlled with a water-perfused suit covering the entire body except for the head and arms. Esophageal temperature (Tes) was measured as an index of internal temperature. In part A (rest), raising Tsk at rest from 31.9 +/- 0.3 to 36.7 +/- 0.2 degrees C increased CVC at control sites from 3 +/- 0.2 to 5 +/- 0.6% of CVCmax. CVC did not change at BT-treated sites, suggesting that at rest, with a normal internal temperature, reflex effects of raising Tsk on SkBF are mediated through vasoconstrictor withdrawal. In part B (exercise), exercise at a low Tsk increased Tes to 37.49 +/- 0.1 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203598 TI - Baroreflex modulation of blood pressure and heart rate variabilities in rats: assessment by spectral analysis. AB - The role of the baroreflex in the spectral characteristics of mean arterial pressure (MAP) and heart rate (HR) was investigated in 12 control rats and 9 rats with chronic sinoaortic baroreceptor denervation (SAD) during 1) basal conditions and 2) ganglionic blockade with chlorisondamine and restoration of the basal MAP level. In SAD rats, power spectral density of MAP, estimated by a fast Fourier transform, was reduced in the low-frequency (LF, 0.27- to 0.74-Hz) band. Ganglionic blockade highly decreased LF power spectral density of MAP in control rats. No relationship was found between the MAP response to chlorisondamine, taken as an index of the sympathetic vasomotor tone, and the basal LF power spectral density. Transfer function analysis between MAP and HR showed that, in control rats, coherence was high for frequencies surrounding the LF and high frequency peaks. In SAD rats, coherence was abolished in the LF band but maintained in the high-frequency band. In conclusion, approximately 80% of the LF power spectral density of MAP depends on the sympathetic nervous system activity, and the baroreflex accounts for one-half of this power and for the coherence between MAP and HR oscillations in the LF band. PMID- 8203599 TI - Open Na+ channel blockade: multiple rest states revealed by channel interactions with disopyramide and quinidine. AB - In voltage-clamp studies of atrial myocytes exposed to disopyramide or quinidine, pulse-train stimulation revealed use-dependent block that increased with increased pulse amplitude. Use-dependent block also became negligible at hyperpolarized holding potentials (< -150 mV), consistent with either rapid unbinding at the holding potential or trapping of the drug in a drug-complexed rest conformation followed by rapid unbinding during the next channel opening event. To explore the unbinding properties of hypothetically different rest blocked conformations, we exposed cells to a postdepolarization "conditioning" potential after channels had become fully inactivated so as to vary the transition to different hypothetical rest-blocked channels. Pulse-train stimulation from -130 to -30 mV generated only a small amount of use-dependent block. Inserting a 120-ms subthreshold (e.g., -100 mV) postdepolarization conditioning potential before return to -130 mV increased use-dependent block. The fraction of steady-state block exhibited a bell-shaped dependence on the conditioning potential. These results are consistent with the existence of a mixture of rest-blocked channel conformations, each having direct access to the blocked-inactivated state. These intermediate rest conformations display radically different drug unbinding rates. PMID- 8203600 TI - Adenosine receptor-mediated relaxation of porcine coronary artery in presence and absence of endothelium. AB - This study was designed to investigate the effects of a series of adenosine analogues on porcine coronary artery in vitro. In both endothelium-intact and denuded rings, 5'-(N-ethylcarboxamido) adenosine (NECA), 2-[p-(2 carboxyethyl)]phenylethylamino-5'-N-ethylcarboxamidoadenos ine (CGS-21680), 2 chloroadenosine (CAD), N6-R-phenylisopropyladenosine (R-PIA), 2 phenylaminoadenosine (PAA), N6-cyclohexyladenosine (CHA), N6-cyclopentyladenosine (CPA), and N6-S-phenylisopropyladenosine (S-PIA) produced concentration-dependent relaxations. The rank order of potency was consistent with A2-adenosine receptor identification. The xanthine adenosine antagonist, 8-(sulfophenyl) theophylline (8-SPT), attenuated the relaxant responses to all the agonists in the endothelium intact rings and to only CAD, R-PIA, PAA, CHA, CPA, and S-PIA in the denuded preparations. Except for NECA and CGS-21680, the slopes of the relaxation curves and the dissociation constant (Kb) values for 8-SPT were similar for all agonists. In addition, endothelium removal selectively reduced the responses to NECA and CGS-21680. The adenosine receptor agonist, CGS-22988, also relaxed the denuded rings in a manner insensitive to blockade by 8-SPT. The data suggest that multiple A2-adenosine receptors exist on the smooth muscle and endothelium of porcine coronary artery, mediating relaxation. Whereas the smooth muscle contains both xanthine-sensitive and -insensitive A2-receptors, which can be activated by a wide range of adenosine agonists, the endothelium possesses xanthine-sensitive receptors that can be stimulated selectively by certain adenosine agonists, including 5'-uronamide derivatives, such as NECA and CGS-21680. The smooth muscle also appears to contain xanthine-insensitive A4-receptors activated by CGS 22988.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203601 TI - Ventricular overdrive pacing-induced anti-ischemic effect: a conscious rabbit model of preconditioning. AB - To study whether ventricular overdrive pacing (VOP) induces preconditioning, rabbits were equipped with right ventricular electrode catheters for pacing and intracavital recording and polyethylene cannulas in the left ventricle and right carotid artery to measure intraventricular pressure and blood pressure. One week after surgery in conscious animals, VOP at 500 beats/min over 2, 5, or 10 min resulted in an intracavital S-T segment elevation, shortening of ventricular effective refractory period, decrease in maximum rate of pressure development and blood pressure, and increase in left ventricular end-diastolic pressure proportional to the duration of stimulation. A 5-min preconditioning VOP applied 5 or 30 min before a 10-min VOP markedly attenuated ischemic changes, whereas a 2 min VOP had no effect. In anesthetized rabbits, a 5-min VOP slightly increased guanosine 3',5'-cyclic monophosphate (cGMP) and profoundly elevated adenosine 3',5'-cyclic monophosphate (cAMP) content in left ventricular samples. When this VOP was preceded (5 or 30 min) by a preconditioning VOP, the cAMP increase was significantly attenuated, whereas the cGMP increase was amplified. We conclude that a single 5-min VOP induces preconditioning in association with alterations in cardiac cyclic nucleotide contents. PMID- 8203602 TI - Nucleoside-induced arteriolar constriction: a mast cell-dependent response. AB - Adenosine (Ado) is a potent vasodilator that has occasionally been shown to cause vasoconstriction. Constrictor responses are generally attributed to A1-receptor stimulation or interactions with the renin-angiotensin system. We describe a previously unreported vasoconstrictor action of Ado and inosine (Ino) in hamster cheek pouch arterioles and examine the mechanism by which these nucleosides induce constriction. Arterioles were dissected from male Golden hamster cheek pouches, transferred to a 37 degrees C tissue chamber, and cannulated at both ends. Changes of luminal diameter in response to Ado were measured to generate cumulative concentration-response curves. The concentration-response curves were biphasic: 10(-6) M Ado elicited an intense, transient constriction, and higher concentrations induced dilator responses. Pretreatment with 8(p sulfophenyl)theophylline, an Ado receptor antagonist, inhibited the dilator responses but did not alter the constriction. Inhibition of Ado uptake with S-(4 nitrobenzyl)-6-thio-inosine eliminated the constrictor response without altering dilator responses. Similar effects were found after pretreatment with an Ado deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride. Finally, Ino, a metabolite of Ado, induced constrictions of similar magnitude to those seen with Ado, but at higher concentrations. The constrictor response was focal in nature, suggesting discrete sites of action of Ado. Methylene blue staining after Ado application revealed degranulated mast cells closely associated with the vessel wall, indicating a possible role for mast cell degranulation in the constrictor response. Supporting this idea were the observations that inhibition of degranulation by 10 microM cromolyn blocked the constrictor response, and compound 48/80 (a mast cell secretagogue) caused constriction similar to that elicited by Ado.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203603 TI - Effects of acidosis and alkalosis on mechanical properties of hypertrophied rat heart fiber bundles. AB - Effects of alkalosis (pH 7.4) or acidosis (pH 6.8) on the intrinsic mechanical properties of control and pressure-overloaded rat hearts were studied in Triton X 100-treated left ventricular fiber bundles. In control bundles, Ca sensitivity [pCa required for one-half maximal response (pCa50)] was 5.520 +/- 0.012 at pH 7.1. Alkalosis increased it by 0.357 +/- 0.018 pCa unit, whereas acidosis decreased it by 0.365 +/- 0.014 pCa unit with no change in Hill coefficient. Maximal tension was decreased by acidic pH and increased by alkaline pH. Stiffness was measured by the response to quick length changes. Acidosis decreased maximal stiffness but increased the stiffness-to-force ratio, whereas alkalosis increased maximal stiffness but had no effect on stiffness-to-force ratio, suggesting that acidosis decreased the force generated per cross bridge. Alkalosis increased the time constant of tension recovery following a quick stretch from 10.6 +/- 0.66 to 17.45 +/- 1.83 ms, suggesting a decreased cross bridge cycling rate. Pressure overload induced by thoracic aortic stenosis for 4 6 wk led to a 200% cardiac hypertrophy associated with a shift from fast to slow ventricular myosin. pCa50 of hypertrophied bundles was not different from control (5.541 +/- 0.012). Ca sensitivity was increased by 0.383 +/- 0.008 in alkaline medium and decreased by 0.325 +/- 0.009 in acidic medium. Stiffness-to-force ratio was decreased in acidic pH, and the time constant of tension recovery was increased from 31.0 +/- 0.4 to 34.9 +/- 0.25 ms by alkalosis. In hypertrophied bundles, maximal tension was decreased by acidic pH but not changed by alkalosis. These results show that in the small pH range of our study 1) pH changes have symmetrical effects on Ca sensitivity in both control and hypertrophied bundles, 2) a decrease or an increase in H+ concentration does not have symmetrical effects on the mechanics of the cross bridges, and 3) changes in the phenotype of contractile proteins induced by aortic stenosis do not influence Ca sensitivity, only moderately influence the response to pH changes, and mainly affect the cross bridge cycling rate. PMID- 8203604 TI - Effects of LTD4 and its specific antagonist L-660,711 in isolated rat hearts with chronic myocardial infarction. AB - We investigated the effects of leukotriene (LT) D4 and its novel potent and selective antagonist L-660,711 on isolated rat hearts with chronic myocardial infarction. The left coronary artery was ligated permanently or for 30 or 60 min and followed by reperfusion. Hearts were isolated and perfused in the Langendorff mode 4 days, 4 wk, or 8 wk after the operation. Dose-response curves for LTD4 (12 240 ng/min) on coronary flow were shifted to the left in rats with permanent coronary occlusion for 8 wk or with coronary occlusion for 30 or 60 min and reperfusion for 4 wk. In contrast, dose-response curves were unchanged in rats 4 days after myocardial infarction. L-660,711 shifted dose-response curves for LTD4 on coronary flow to the right in all groups. The negative inotropic and chronotropic effects of LTD4 could be markedly attenuated by L-660,711 in all groups. Our findings suggest that the effect of LTD4 is enhanced in rat hearts with chronic myocardial infarction. L-660,711 effectively antagonized the vasoconstrictor effect of exogenous LTD4. PMID- 8203605 TI - Mechanism of redistribution of cerebral blood flow during hypercarbia and seizures. AB - After occlusion of an artery to the brain, hypercarbia and seizures may produce a paradoxical reduction in cerebral blood flow to the region supplied by collateral vessels. We measured pressure in an occluded branch of the middle cerebral artery and measured regional cerebral blood flow (rCBF) to collateral-dependent cerebrum in dogs (n = 25) to examine hemodynamic mechanisms that account for the reduction in flow. During hypercarbia (arterial PCO2 = 70 +/- 5 mmHg), rCBF to collateral dependent cerebrum, measured with microspheres and identified using the shadow flow technique, decreased from 95 +/- 6 (mean +/- SE) to 71 +/- 9 ml.100 g-1.min 1 (P < 0.05), while flow to normal brain increased from 105 +/- 9 to 281 +/- 15 ml.100 g-1.min-1 (P < 0.05). Pressure in a branch of the middle cerebral artery decreased during hypercarbia from 50 +/- 6 to 25 +/- 3 mmHg (P < 0.05), concurrent with a significant increase in resistance of collateral vessels. Small vessel resistance was the same in collateral-dependent and normal brain. During bicuculline-induced seizures, with blood pressure maintained at control levels by withdrawal of blood, rCBF decreased in collateral-dependent cerebrum from 128 +/- 16 to 67 +/- 11 ml.100 g-1.min-1 (P < 0.05), and flow to normal brain increased from 169 +/- 14 to 418 +/- 17 ml.100 g-1.min-1 (P < 0.05). Small vessel resistance decreased in both regions, but the decrease was much greater in normal cerebrum. Changes in cerebral artery pressure and resistance of collateral vessels during seizure were similar to those during hypercarbia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203606 TI - Cellular functions of diabetic cardiomyocytes: contractility, rapid-cooling contracture, and ryanodine binding. AB - To study the mechanisms of cardiac dysfunction in experimental diabetes, adult rat cardiomyocyte shortening (measured with a video edge-detector system), the sarcoplasmic reticulum (SR) Ca2+ content [assessed by rapid-cooling contracture (RCC) and caffeine contracture (CC)] was examined. Ryanodine binding to the SR Ca(2+)-release channel of myocardium homogenate was also studied. Myocytes from diabetic rats showed depressed shortening (44% decrease compared with controls), reduced maximum rates of shortening and relengthening (58 and 56% decrease, respectively), and prolonged time to peak shortening (47% increase). RCCs and CCs from diabetic cells were 68 and 75% of the control values, respectively. Most of these cardiomyocyte abnormalities were corrected by daily insulin treatment in the diabetic rats. Ryanodine binding parameters indicated that the number of high affinity binding sites was decreased in diabetic hearts. These data suggest that changes in contractile parameters as measured in diabetic myocytes are in good agreement with data obtained from intact heart or cardiac tissue preparations. Decreased SR Ca2+ content and reduced ryanodine binding sites indicate that the SR functions of storage and release of Ca2+ were depressed. This consequently may cause depressed contraction in diabetic hearts. PMID- 8203607 TI - Control of oxidative metabolism in volume-overloaded rat hearts: effects of different lipid substrates. AB - The relationship between intracellular energy parameters and myocardial O2 consumption (VO2) was studied in control and volume-overloaded hearts perfused with different lipid substrates and over a range of left ventricular work loads. In control hearts, a unique linear relationship between log of cytosolic [ATP]/[ADPf].[Pi] (where [ADPf] is concentration of free ADP) and myocardial VO2 was observed between low and high work loads for both fatty acids studied. In volume-overloaded hearts perfused in the presence of exogenous palmitate, the slope of the relationship between log [ATP]/[ADPf].[Pi] and myocardial VO2 was considerably depressed. It would seem that, under these conditions, much of the thermodynamic control of respiratory chain function has been lost. When myocardial VO2 was expressed as a function of cytosolic ADPf, the cytosolic ADPf was not regulatory. This may be related to a substrate limitation of the respiratory chain, as suggested by an excessive oxidation of pyridine nucleotides. When octanoate, instead of palmitate, was used, most of the above limitation of the respiration disappeared. With this substrate, the reduction of mitochondrial pyridine nucleotides in volume-overloaded hearts was similar to that in controls, and the linear relationship between log [ATP]/[ADPf].[Pi] and myocardial VO2 reappeared over the range of work loads studied. The above failure of cytosolic phosphate potential and ADPf to drive respiration when mitochondrial NADH is low fits well with the integrated model of kinetic regulation, as proposed by recent nuclear magnetic resonance studies. our results also indicate that, even at high respiratory rates, free-energy change of ATP synthesis of volume-overloaded hearts can be protected by use of an appropriate substrate. This, in turn, prevents contractile failure. PMID- 8203608 TI - Formation and action of a P-450 4A metabolite of arachidonic acid in cat cerebral microvessels. AB - The purpose of this study was to determine whether arachidonic acid can be converted to 20-hydroxyeicosatetraenoic acid (HETE) by P-450 enzymes in cat cerebral microvasculature, to identify the P-450 isoforms responsible for the formation of this metabolite, and to characterize the vasoactive effects of 20 HETE on these vessels. Cerebral microvessels were isolated by filling them with a suspension of magnetized iron oxide (particle size = 10 microns) and separated from minced cerebral cortical tissue using a magnet. Cat cerebral microvessels were homogenized and incubated with [14C]arachidonic acid (AA), and cytochrome P 450-dependent metabolites of AA were separated by reverse-phase high-pressure liquid chromatography. A major metabolite that coeluted with synthetic 20-HETE was identified. The formation of this metabolite was dependent on NADPH and was inhibited by 17-octadecynoic acid (ODYA), a specific suicide-substrate inhibitor of the omega-hydroxylation of AA by P-450 enzymes. Western blot analysis confirmed the presence of a P-450 enzyme of the 4A gene family in cat cerebral microvessels. Gas chromatography/mass spectrometry analysis revealed that this metabolite has an identical mass-to-charge ratio (391 m/z) as that of standard 20 HETE. Exogenous 20-HETE constricted pressurized cat pial arteries in a concentration-dependent manner with a threshold concentration of < 1.0 nM. 20 HETE (1 nM) inhibited the activity of a 217-pS K+ channel recorded in cell attached patches of isolated cat cerebral microvascular muscle cells. Blockade of endogenous P-450 activity with 17-ODYA markedly increased the activity of the 217 pS K+ channel in these cells, an action that was completely reversed by a nanomolar concentration of 20-HETE, suggesting that 20-HETE might be an endogenous modulator of the 217 pS K+ channel in cerebral arterial muscle cells. These results demonstrate the presence of P-450 4A enzyme activity in the cerebral microvasculature of the cat that converts AA to 20-HETE. The potent vasoconstrictor effects of 20-HETE on cerebral vessels suggests that metabolites of P-450 enzymes of the 4A gene family could play an important role in regulating cerebral microvascular tone. PMID- 8203609 TI - Involvement of nitric oxide and nitrosothiols in relaxation of pulmonary arteries to peroxynitrite. AB - Peroxynitrite (ONOO-) is an inflammatory cell-derived oxidant, formed by the reaction of superoxide anion (O2-) with nitric oxide (NO), which was recently reported to relax vascular tissues. In the present study, the potential role of NO in the mechanism of relaxation in isolated bovine endothelium-denuded pulmonary arterial smooth muscle rings to ONOO- was evaluated. Potassium preconstricted pulmonary arterial rings rapidly relaxed for a prolonged period of time on exposure to ONOO- (0.01-0.1 mM). The relaxation after 1 min of exposure to ONOO- (0.1 mM) was reduced 49 and 87%, respectively, by inhibitors of the stimulation of soluble guanylate cyclase, methylene blue, and LY-83583. In contrast, a scavenger of hydroxyl radicals, dimethyl sulfoxide, did not alter this response. Decomposed 0.1 mM ONOO- (which is primarily nitrite) and 0.1 mM nitrite caused a relaxation of pulmonary artery, which slowly developed over 15 min. Small quantities of NO were detected by chemiluminescence quantification methods when ONOO- was added to buffer. Exposure of pulmonary arterial tissue or buffer containing glutathione (GSH) to ONOO- caused a time-dependent increase in the observed generation of NO, whereas decomposed ONOO- produced 10% of the NO generated by ONOO- on incubation with pulmonary arterial tissue. Treatment with diethyl maleate, an agent that depletes tissue GSH, reduced both the relaxation and the formation of NO detected from pulmonary artery on exposure to ONOO-. GSH solutions treated with ONOO- appear to have generated a nitrosothiol-like vascular relaxant compound. Thus ONOO- appears to relax vascular tissue, in part, by nitrosylating tissue GSH (or other thiols), which subsequently releases NO over prolonged time periods. PMID- 8203610 TI - Attenuation of blood flow-induced dilation in arterioles after muscle contraction. AB - The response of third-order arterioles (n = 15) in rat cremaster muscle to increased luminal flow was studied after brief (20-30 s) occlusion of a neighboring arteriole in pentobarbital-anesthetized rats. Red cell velocity increased almost fivefold (485 +/- 54% of control) during occlusion, and vessel diameter increased 63 +/- 11%. Initially, the calculated wall shear rate increased to 430 +/- 40% of control during occlusion but then decreased to 308 +/ 35% of control as a consequence of arteriolar dilation. The muscle was subsequently stimulated to contract for 1 min, and the occlusion procedure was repeated after arteriolar diameter and red cell velocity had returned to control levels. In this instance the vessel dilation was 34 +/- 10% or about one-half of that seen during the previous occlusion, although velocity and shear rate rose to a similar degree (474 +/- 54 and 397 +/- 35%, respectively). Dilation during a third occlusion 2-7 min after the vessel recovered from the second occlusion was as great as during the first occlusion (77 +/- 20%). The results indicate that flow-induced dilation in arterioles of rat cremaster muscle is transiently attenuated after muscle contraction. PMID- 8203611 TI - Effects of heat stress on vascular capacitance. AB - In dogs and humans, heat stress is associated with an increase in cardiac output that sustains blood flow to heat-dissipating organs. Because cardiac output and venous return are equal in the steady state, the circulation must also adjust in heat stress to allow the venous return to increase. To analyze these adjustments, we measured blood volumes, unstressed volumes, blood flow distribution, venous compliance, venous resistance, and the time constant of venous drainage of the splanchnic and extrasplanchnic vascular beds in dogs anesthetized with alpha chloralose at normal and at high core temperatures. We repeated the measurements at high core temperatures with ganglionic blockade, alpha-adrenergic receptor blockade, or beta-adrenergic receptor blockade to determine the efferent neurohumoral pathway. When core temperature was increased from 37.8 +/- 0.2 to 41.9 +/- 0.1 degrees C, total splanchnic blood volume decreased 23% (4.6 +/- 1.4 ml/kg) and splanchnic unstressed volume decreased 38.5%. None of the other determinants of venous return changed. Ganglionic blockade shifted the total and unstressed splanchnic blood volume during heat stress back to normothermic values. However, beta- and alpha-blockade did not affect splanchnic volumes. We conclude that a decrease in splanchnic unstressed volume is an important factor for the increased venous return during heat stress. Although mediated through sympathetic ganglions, this decrease is not abolished by alpha- or beta-receptor blockade. PMID- 8203612 TI - Cytosolic [Ca2+] measurements in endothelium of rabbit cardiac valves using imaging fluorescence microscopy. AB - Cytosolic Ca2+ plays a critical role in the secretion of endothelium-derived factors. A new preparation that allows fluorescence imaging of intracellular free Ca2+ concentration ([Ca2+]i) in endothelial cells of rabbit cardiac valves is described. Electron micrographs of the valves revealed no underlying smooth muscle cells that might influence endothelial cell responses or contribute to [Ca2+]i signaling. The valve leaflets, which were < 100 microns in diameter, were visualized using a specially designed chamber and a long working distance fluorescence objective. The semilunar valves (pulmonary and aortic) responded to endothelium-dependent vasodilators, including acetylcholine, with an increase in [Ca2+]i. Synchronized [Ca2+]i transients were observed in the endothelial monolayer in response to agonist stimulation in K(+)-free solutions. The ability to monitor changes in [Ca2+]i in a native endothelial monolayer provides a more realistic assessment of stimulus-response coupling within individual cells and communication between cells of native endothelium. In addition, this preparation affords an opportunity for comparative studies of endothelium-related pathophysiologies, which can be induced experimentally in animal models. PMID- 8203613 TI - Measuring activation patterns of the heart at a microscopic size scale with thin film sensors. AB - To study the spread of excitation in ventricular heart preparations we have designed a fast, high-resolution recording and mapping system. Papillary muscles were dissected from the isolated guinea pig hearts. The preparation was fixed in a tissue bath and superfused with Tyrode solution. Linear and two-dimensional arrays of Ag/AgCl electrodes were made on glass with a thin-film technique. The transparent sensors with up to 24 electrodes (spaced 50, 90, or 180 microns apart) were positioned close to the surface of the preparation with a custom designed three-dimensional micromanipulator. Extracellular signals were simultaneously recorded by a 24-channel data acquisition system with a 200 kHz per channel sample rate, with 12-bit amplitude resolution and a maximum data length of up to 3 MB. Digitized video images of the electrode array and the underlaying preparation were used to identify the locations of the recording sites. A UNIX-based computer system with a custom-designed data acquisition and database program was used to control the instruments and to manage the experimental data. This technique gave signals with excellent signal-to-noise ratios (up to 65 dB) and permitted accurate evaluation of the time and the site of the local activation with high resolution (to within 5 microseconds, 50 microns). We describe the spread of excitation within the area of a few cells and found a substantial dispersion of conduction velocities. Beat-to-beat comparison of activation patterns showed relatively small variations in the spread of excitation (a few microseconds). PMID- 8203614 TI - Dissociation of heart rate variability from parasympathetic tone. AB - Time and frequency domain measurements of heart rate variability have been used as indexes of parasympathetic tone. This study evaluates the effects of parasympathetic stimulation on these indexes. Ten normal subjects (5 females, 5 males; age 27.4 +/- 5.1 yr) were evaluated in the Clinical Research Center. Five minute electrocardiographic recordings were obtained at baseline and during 1) combined alpha-adrenergic stimulation with baroreflex-increased cardiac parasympathetic activity produced by phenylephrine infusion; 2) parasympathetic blockade (atropine 0.04 mg/kg); and 3) isolated alpha-adrenergic stimulation produced by phenylephrine infusion after parasympathetic blockade. The infusion rate of phenylephrine was titrated to increase the systolic blood pressure by 20 30 mmHg. Heart rate variability analysis was performed using standard time and frequency domain parameters. Phenylephrine infusion resulted in a decrease in the time domain measures and in the high-frequency power. After parasympathetic blockade, alpha-adrenergic stimulation had no significant effect on the heart rate variability parameters. These findings suggest that the heart rate variability parameters traditionally associated with parasympathetic tone do not always reliably measure parasympathetic tone, since they decrease with baroreflex parasympathetic stimulation. PMID- 8203615 TI - Insulin sensitivity of adipocytes from inbred mouse strains resistant or sensitive to diet-induced obesity. AB - We evaluated insulin sensitivity in epididymal adipocytes from two mouse strains shown to be either sensitive (AKR/J, n = 14) or resistant (SWR/J, n = 12) to the development of obesity when fed a high-fat diet. Half of each strain was fed a chow (CH) diet (12% fat), and half received a sweetened condensed milk (CM) diet (33% fat). After 1 wk, epididymal adipose depots were removed and digested with collagenase, and glucose transport was measured with labeled 2-deoxyglucose. Plasma glucose and insulin were slightly higher in AKR/J than SWR/J mice (glucose: 139.7 vs. 118.8 mg/dl, P < 0.06; insulin: 3.45 vs. 2.99 ng/ml, P < 0.04). One week of high-fat feeding increased adipose depot mass and carcass lipid in both strains to approximately the same extent. Adipocytes from AKR/J mice had greater insulin-stimulated glucose transport compared with SWR/J mice at both submaximal and maximal insulin levels (P < 0.0001). Short-term feeding of the high-fat diet increased AKR/J adipocyte insulin sensitivity but decreased the sensitivity of SWR/J adipocytes to insulin. The differences in adipocyte insulin sensitivity between strains were not explained by differences in adipocyte cell size. Access to the high-fat CM diet for 12 wk increased total dissected adipose depot size by 209% in the AKR/J mice and 82% in the SWR/J mice. These data clearly demonstrate that the two strains differ in adipocyte insulin sensitivity as well as sensitivity to dietary obesity. Increased adipocyte insulin sensitivity could contribute to a predisposition to increase adipose tissue lipid stores with diets high in fat content. PMID- 8203616 TI - Extravascular protein in the renal medulla: analysis by two methods. AB - Two methods have been used to test for the presence of extravascular protein in the interstitium of the renal inner medulla. First, ascending vasa recta (AVR) segments were perfused with buffer containing 5 g/dl of albumin. The hydraulic pressure in the perfused vessel was varied to control transmembrane volume flux (Jv) to the interstitium. Interpolation to the point of zero Jv was employed to estimate interstitial Starling forces in the hydropenic rat papilla. Analysis of those experiments predicts that interstitial protein concentration (Ci) is high. When AVR segments are filled with oil, the oil column spontaneously breaks up as fluid is secreted into the lumen from the papillary interstitium. To obtain a lower limit on Ci, isolated AVR segments (IAS) filled with oil were sampled to measure protein concentration in the secreted fluid. In hydropenic rats, protein concentration was 3.4 +/- 0.5 and 5.2 +/- 0.2 g/dl in IAS and adjacent free flowing AVR, respectively (P < 0.01). In rats subjected to furosemide and saline diuresis, the values were nearly identical, 4.7 +/- 0.2 and 5.2 +/- 0.2 g/dl, respectively. These separate experimental approaches corroborate a high concentration of protein in the renal inner medullary interstitium. PMID- 8203617 TI - Effects of ANG-converting enzyme and alpha 1-adrenoceptor inhibition on intrarenal hemodynamics in SHR. AB - To investigate the prolonged effects of angiotensin-converting enzyme (ACE) inhibition and alpha 1-adrenoceptor blockade on intrarenal hemodynamics, whole kidney and renal micropuncture studies were performed in male 21-wk-old Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats treated for 3 wk with quinapril (3 mg/kg), terazosin (1 mg/kg), or in their combination (quinapril 1.5 mg/kg and terazosin 0.5 mg/kg). In WKY, only quinapril significantly reduced mean arterial pressure (MAP) associated with reduced afferent arteriolar resistance; there were no other significant changes. In contrast, all treatments similarly decreased MAP in SHR. Quinapril increased renal plasma flow and decreased filtration fraction. With respect to intrarenal hemodynamics, quinapril increased single-nephron plasma flow and reduced glomerular capillary pressure (from 53.1 to 47.8 mmHg; P < 0.01), associated with reduced afferent (from 4.80 to 3.17 10(10)dyn.s.cm-5; P < 0.01) and efferent (from 1.70 to 1.17 10(10)dyn.s.cm-5; P < 0.01) arteriolar resistances, and increased ultrafiltration coefficient (from 0.037 to 0.052 nl.s-1.mmHg-1; P < 0.05). Terazosin only reduced arteriolar resistance. The combined treatment attenuated either agent's independent effects on glomerular hemodynamics. These data demonstrate that prolonged ACE and adrenergic inhibition therapy alone or in combination produce different effects than when given by vein, suggesting that prolonged renopressor system inhibition may be more effective than adrenergic in SHR. PMID- 8203618 TI - Adaptation of muscle glucose transport with caloric restriction in adult, middle aged, and old rats. AB - The effects of prolonged caloric restriction (60% of ad libitum intake initiated at 14 wk of age) on glucose transport activity in isolated epitrochlearis muscles were studied in female Fischer 344 rats aged 8, 18, and 23 mo. Basal 3-O methylglucose transport (3-MG) rate (without insulin) was not significantly altered by caloric restriction. With a submaximally effective insulin concentration (75 microU/ml), 3-MG transport was enhanced in the caloric restricted groups by 59, 59, and 105% at 8, 18, and 23 mo of age, respectively. With a maximally effective insulin concentration (20,000 microU/ml), 3-MG transport was increased after caloric restriction, despite no change in muscle GLUT4 glucose transporter protein content. These results indicate that chronic caloric restriction enhances insulin stimulation of the glucose transport system independent of changes in basal glucose transport or muscle GLUT4 levels, and insulin-stimulated glucose transport is enhanced in rats with chronic caloric restriction at least until 23 mo of age. PMID- 8203619 TI - Role of endogenous vasopressin in development of gastric ulcer induced by restraint and water immersion. AB - To elucidate the role of arginine vasopressin (AVP) in the development of stress induced gastric ulcer, the mucosal lesions after restraint and water immersion were examined in Brattleboro strain rats with hereditary hypothalamic diabetes insipidus (DI) and in Long-Evans rats (LE) used as controls. Restrained animals were immersed in water for 2 h, and the size of lesion was expressed as percentage of the lesion area to the total glandular mucosal area, which were defined as ulcer index (UI). In DI rats, UI was significantly higher than in control LE rats, despite the attenuated responses of plasma adrenocorticotropic hormone (ACTH) to stress. Although subcutaneous injection of selective antidiuretic analogue 1-desamino-8-D-AVP did not affect UI, intracerebroventricular (icv) administration of AVP reduced UI in DI rats, and icv administration of V1 antagonist [d(CH2)5Tyr(Me)]AVP elevated UI in LE rats. These results indicate that endogenous AVP plays a role in preventing the formation of gastric ulcers induced by stress via a central V1 receptor. Furthermore, we suggest that elevation of ACTH in plasma is not essential in the development of stress-induced gastric ulcer in rats. PMID- 8203620 TI - Circadian rhythms and time course of adaptive sodium and potassium excretion in rats after uninephrectomy. AB - The relationship between renal circadian cyclic excretion and renal compensatory adaptation after uninephrectomy for K, Na, and water was studied. Rats in a 12:12 h light-dark environment were given a liquid diet, and urine was collected for 16 days with consecutive 90-min periods. Days 1-4 were control, 5-10 followed a sham operation, and 11-16 followed uninephrectomy. The major findings were 1) the circadian cycles in excretion were virtually unchanged after sham and uninephrectomy; 2) an adaptive increase in excretion of Na, K, and water by the remaining kidney occurred within 90 min after uninephrectomy; 3) after uninephrectomy the distribution of the 24-h increment in excretion for the remaining kidney closely followed the preexisting pattern of circadian excretion for Na but was evenly distributed between light and dark phases for K; and 4) after uninephrectomy the ratio of excretion to intake was unchanged. This is the first study to document the time course of adaptation to uninephrectomy using consecutive brief collections over several days in unanesthetized and undisturbed rats. Adaptation after uninephrectomy occurred essentially immediately; was maintained unchanged; and preserved Na, K, and water homeostasis. Uninephrectomy did not alter the circadian control of excretion. PMID- 8203621 TI - Effect of intrahypothalamic insulin on sympathetic nervous function in rats drinking a high-sucrose solution. AB - Hyperinsulinemia has been associated with increased sympathetic nervous activity. However, direct injection of insulin into the hypothalamus of anesthetized rats produces sympatho-inhibition. This discrepancy could be due to confounding effects of anesthesia or insulin resistance on central neural function. The effect of injecting saline or insulin (3.0 or 30 mU) into the ventromedial hypothalamus on mean arterial pressure, heart rate, and renal nerve activity (RNA) was investigated in conscious rats and in rats anesthetized with urethan or pentobarbital. Insulin decreased RNA in conscious rats but had no effect in pentobarbital-anesthetized rats. In urethan-anesthetized rats with hyperglycemia, the insulin increased RNA. Drinking a 10% sucrose solution enhanced the sympathoexcitatory effect of insulin in the urethan-anesthetized rats but had no effect in the other two groups. The sucrose solution did not affect insulin sensitivity in any group; however, urethan anesthesia did produce insulin resistance. These data show that central effects of insulin are sensitive to anesthesia and do not support a sympathoexcitatory role for insulin in the ventromedial hypothalamus of conscious rats, at least in relation to the renal sympathetic nerves. PMID- 8203623 TI - Effects of temperature and freezing on hepatocytes isolated from a freeze tolerant frog. AB - Metabolically active hepatocytes prepared from freeze-tolerant wood frogs, Rana sylvatica, were used to examine the direct effects of temperature and freezing on cryoprotectant synthesis and to assess the effectiveness of the natural cryoprotectant glucose in the freezing preservation of the isolated cells. Freshly isolated hepatocytes showed slow leakage of lactate dehydrogenase, readily synthesized urea, and oxidized a variety of 14C-labeled substrates. Effects of temperature on glucose production by isolated hepatocytes showed a normal Arrhenius relationship. However, compared with 0 degrees C control cells, either incubation at higher temperatures or freezing at -3 degrees C reduced the activity of glycogen phosphorylase alpha. These data suggest that the freezing induced cryoprotectant production that occurs in vivo is not due to direct action of either low temperature or freezing on liver cell metabolism. The natural cryoprotectant glucose was also an excellent cryoprotectant of hepatocytes in vitro. In the absence of glucose, freezing caused a substantial leakage of lactate dehydrogenase from isolated hepatocytes, the rate of leakage increasing as freezing temperature decreased. Addition of 200-600 mM glucose to the incubation medium (similar to natural levels) fully protected cells against damage during freezing at -4 or -8 degrees C, normal freezing temperatures experienced by these frogs. Glucose also greatly improved freezing survival of isolated frog hepatocytes at ultralow temperatures (-80 or -196 degrees C). PMID- 8203622 TI - Angiotensin II and alpha 1-adrenergic tone in chronic nitric oxide blockade induced hypertension. AB - Nitric oxide (NO) is a tonically produced vasodilator that maintains blood pressure (BP) in the normal animal. In these studies, we produced chronic NO blockade by oral administration of the NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME), which produced sustained hypertension and increased renal vascular resistance (RVR) in conscious rats. Acute blockade of the angiotensin II type 1 (AT1) receptor with losartan had little effect on BP and RVR in either chronically NO-blocked or normal conscious rats. Acute blockade of the alpha 1 adrenoceptor with prazosin produced moderate similar falls in BP in both chronically NO-blocked and normal rats. The combination of AT1 and alpha 1 adrenoceptor blockade was profoundly antihypertensive and was particularly effective in lowering BP in chronically NO-blocked rats where the hypertension was obliterated. In contrast, the increased RVR persisted in chronically NO blocked rats receiving combined acute AT1 and alpha 1-adrenoceptor blockade. These observations indicate that, in the sustained phase of chronic NO blockade, the hypertension is largely due to the combined activities of alpha 1 adrenoceptor and AT1 stimulation. PMID- 8203624 TI - Role of central chemoreceptors in behavioral thermoregulation of the toad, Bufo marinus. AB - We tested the hypothesis that hypercapnia will induce behavioral hypothermia in toads and that central chemoreceptors are involved in this response. Animals were tested in an enclosed temperature gradient supplied with different gas mixtures. Fractional inspired CO2 (FICO2) between 0 and 0.05 had no significant effect on selected body temperature, but FICO2 between 0.06 and 0.10 reduced the selected body temperature from U approximately 28 to 18 degrees C. To determine if the hypercapnia-induced hypothermia is mediated by acidification of central chemoreceptors, the pH of the fourth ventricle was kept constant by perfusion with mock cerebrospinal fluid of pH 7.7 or 7.1 (normal and acidic values, respectively). Ventricular perfusion at pH 7.7 under normocapnic conditions had no effect on body temperature. Hypercapnia (FICO2 0.08) failed to induce hypothermia when the fourth ventricle was kept at pH 7.7 and when hyperoxia was present. Acidic ventricular perfusion under normocapnic conditions decreased selected body temperature from 27 to 25 degrees C, a significant drop but much less than that due to hypercapnia producing the same brain pH, suggesting an important role of peripheral chemoreceptors. The physiological significance of behavioral hypothermia and nature of the peripheral stimulus were evaluated by measuring the effect of hypercapnia on arterial oxygen saturation, PO2, and pH at 15 and 25 degrees C. Arterial oxygen saturation was higher at the lower temperature. Increasing FICO2 decreased oxygen saturation at 25 degrees C but not at 15 degrees C. Arterial PO2 increased with increasing inspired CO2. This increase was greater at 15 degrees C than at 25 degrees C. Arterial pH decreased at both temperatures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203625 TI - Postnatal developmental changes in blood flow to choroid plexuses and cerebral cortex of the rat. AB - Postnatal developmental changes in blood flow to choroid plexuses of the lateral (LVCP) and fourth (4VCP) ventricles and cerebral cortex were studied in pentobarbital-anesthetized rats at 2, 3, 5, and 7-8 wk. Blood flow was measured by indicator fractionation with N-isopropyl-p-[125I]iodoamphetamine as the marker. Blood flow to the LVCP and 4VCP was 2.5 +/- 0.1 and 2.7 +/- 0.1 ml.g 1.min-1, respectively, and did not change between the 2nd and 3rd wk. However, it increased by 34% between the 3rd and 5th wk. From the age of 5 wk on, 4VCP was characterized by higher blood flow rates than LVCP. Cerebral cortical blood flow gradually increased between the 2nd and 5th wk. There was no difference in cortical blood flow between 5-wk-old and adult animals. The changes in choroidal blood flow likely represent a continuing adjustment of the choroidal vascular system to steadily increasing secretory capabilities of the maturing choroidal epithelium. PMID- 8203627 TI - Acute hypocapnia blunts natriuretic and diuretic effects of atrial natriuretic factor in rats. AB - Recent studies suggest that the autonomic nervous system, when activated by respiratory alkalosis, may attenuate the renal effects of atrial natriuretic factor (ANF). We evaluated the renal responses to infusion of ANF during acute exposure to hypocapnia in the presence or absence of the renal nerves in anesthetized rats. In this study, renal function during hypocapnia was assessed and was compared with renal function during normocapnia produced by normal ventilation as well as by hyperventilation. Rats were divided into three experimental groups (n = 8): 1) a normally ventilated normocapnic (NV-N) (control) group; 2) a hyperventilated normocapnic (HV-N) group; and 3) a hyperventilated hypocapnic (HV-H) group. The innervated (Inn) right kidney served as a control for the contralateral denervated (DNX) kidney. In Inn and DNX kidneys of HV-H rats, an infusion of ANF (12 micrograms.kg-1.h-1) produced a smaller increase in urine flow rate (delta V: 9.8 +/- 3.9 and 1.3 +/- 4.2 microliters/min) and in fractional Na excretion (delta FENa: 1.35 +/- 0.52 and 0.73 +/- 0.58%) compared with NV-N rats (delta V: 37.6 +/- 4.9 and 59.9 +/- 9.7 microliters/min; delta FENa: 3.24 +/- 0.37 and 3.88 +/- 0.65%). No differences were observed in delta V and delta FENa in Inn kidney between HV-H and HV-N groups; however, the attenuated natriuretic and diuretic responses to ANF in DNX kidney of HV-H rats were also observed in comparison with HV-N rats (delta V: 27.4 +/- 4.3 microliters/min; delta FENa: 2.94 +/- 0.48%). ANF induced natriuresis in DNX kidney to the same degree in NV-N and HV-N rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203626 TI - Sodium appetite, thirst, and body fluid regulation in humans during rehydration without sodium replacement. AB - After a 7-h H2O and Na+ depletion period (DP), produced by intermittent light exercise (8 bouts) at 35 degrees C, we examined thirst and taste palatability responses to 10 different NaCl solutions during 23 h of rehydration (RH) at 25 degrees C. During DP, net H2O and Na+ loss were 27.2 +/- 2.9 ml/kg and 3.29 +/- 0.45 meq/kg, respectively. Plasma osmolality (POsm) and plasma Na+ concentration ([Na+]p) increased significantly during DP by 3.4 +/- 1.2 mosmol/kgH2O and 3.0 +/ 1.0 meq/kgH2O, respectively. Plasma volume (PV) decreased by 6.5 +/- 1.9%. Thirst rating, renal fractional reabsorption of H2O, and plasma arginine vasopressin concentration (PAVP) increased as POsm increased. This increased thirst was accompanied by increased palatability ratings to H2O. During RH, subjects drank deionized H2O ad libitum and ate a Na(+)-free diet for 23 h. POsm and [Na+]p returned to control levels within 1 h RH and remained at or below the control thereafter. PV remained reduced by approximately 5% throughout RH. The increased thirst and PAVP returned to their respective control levels within 1 h of RH as POsm decreased, but thirst rating increased against between 17 and 23 h of RH without increase in POsm or PAVP. Palatability ratings to a 1 M NaCl solution at and after 3 h RH and palatability ratings to 0.3 M at 17 and 23 h RH were significantly higher than control. Plasma aldosterone concentration (PAldo) increased after DP, decreased with drinking, and increased again between 6 and 23 h of RH, accompanied by a marked decrease in fractional Na+ excretion to < 0.07%. Thus both Na+ preference and thirst in humans are influenced by body fluid and electrolyte status. The increased Na+ palatability (Na+ appetite) was preceded by osmotically induced thirst, and accompanied by nonosmotically driven thirst [extracellular fluid (ECF) thirst] and increased PAldo. The "Na+ appetite" and "ECF thirst" along with increased renal Na+ retention could contribute to ECF volume regulation after thermally induced H2O and Na+ depletion. PMID- 8203628 TI - Exogenous arginine vasopressin does not enhance carotid baroreflex control in the conscious dog. AB - Arginine vasopressin (AVP) has profound effects on the cardiovascular system, yet has minimal pressor activity at physiological levels in intact subjects. We designed an investigation to delineate the effects of AVP on open-loop carotid baroreflex control of mean arterial pressure (MAP), total peripheral resistance (TPR), and cardiac output (CO) in conscious, chronically instrumented dogs. During graded infusions of AVP (0.5-2.0 ng.kg-1.min-1), the open-loop hemodynamic responses to controlled changes in isolated carotid sinus pressure (CSP) were determined. Increasing levels of AVP infusion led to significant increases in plasma AVP levels (P < 0.01). Increasing doses of AVP led to significant increases in TPR at all levels of CSP (P < 0.01). The overall range and gain of the response were not significantly different at any level of AVP infusion. Despite this increase in systemic resistance, there was no significant change in the MAP-CSP relationship. Infusion of AVP led to a dose-dependent depression in CO (P < 0.01) and heart rate (HR; P < 0.05) at all levels of CSP with no significant effect on open-loop baroreflex control. We conclude that although exogenous AVP induces profound changes in cardiovascular function, it does not alter carotid baroreflex control of MAP, TPR, CO, and HR. PMID- 8203629 TI - Type II corticosteroid receptor stimulation increases NPY gene expression in basomedial hypothalamus of rats. AB - Evidence has suggested that glucocorticoids may increase neuropeptide Y (NPY) activity and gene expression. In the present study, we sought to determine the corticosteroid receptor subtype through which glucocorticoids increase NPY gene expression in the basomedial hypothalamus. This was accomplished by continuous administration of selective type I and II corticosteroid agonists in adrenalectomized Sprague-Dawley rats. Dot-blot analysis was performed, and the amount of NPY mRNA was determined. Additionally, serum insulin and glucose concentrations were determined. Type II receptor stimulation increased NPY mRNA levels in the basomedial hypothalamus above that of sham animals. This implies that type II receptor stimulation by high physiological concentrations of serum corticosterone may also increase NPY gene expression in the basomedial hypothalamus. The type II receptor agonist-induced increase in NPY gene expression did not appear to be mediated by a decrease in serum insulin concentrations. The present results may have relevance to the increased gene expression of NPY observed in the basomedial hypothalamus of obese Zucker rats and in food-deprived animals. PMID- 8203630 TI - Prostaglandin H2-thromboxane A2 and renal functions in the Lyon hypertensive rat. AB - The influence of renal perfusion pressure (RPP) on renal functions was studied in anesthetized 8-wk-old Lyon hypertensive (LH) and normotensive (LN) rats before and after a specific blockade of prostaglandin (PG) H2-thromboxane (Tx) A2 receptors using GR-32191B. The nervous and hormonal influences on the kidneys were controlled by renal denervation, adrenalectomy, and an infusion of norepinephrine, aldosterone, hydrocortisone, and vasopressin. With the use of inflatable cuffs, RPP was varied from 100 to 125 and then to 150 mmHg. In control conditions, the renal blood flow (RBF) and glomerular filtration rate (GFR) were independent of RPP in both strains. LH kidneys differed from LN controls by an increased preglomerular vasoconstriction as indicated by a similar decrease in RBF and GFR. Moreover, the pressure-natriuresis curve was blunted in LH compared with LN kidneys. GR-32191B did not affect the renal function of LN rats. In LH kidneys, it normalized RBF and renal vascular resistance and improved GFR, whereas it had no effect on the pressure-natriuretic relationship. It is concluded that the elevated preglomerular vascular resistance that characterizes LH rats is dependent on an overstimulation of PGH2-TxA2 receptors whereas these latter are not involved in the control of pressure-natriuresis. PMID- 8203631 TI - On determinants of glomerular filtration rate after inhibition of proximal tubular reabsorption. AB - The carbonic anhydrase inhibitor acetazolamide (ACZ) inhibits the absolute rate of proximal reabsorption (APR), causes a reduction in glomerular filtration rate (GFR), and activates the tubuloglomerular feedback mechanism (TGF) resulting in afferent vasoconstriction. The quantitative importance of the afferent vasoconstriction for the reduced GFR was tested by addition of a vasodilator during continuous infusion of ACZ. Dopamine caused an increase in renal blood flow (RBF) to pre-ACZ levels. Glomerular capillary pressure (Pgc) and proximal tubular pressure (Pprox) increased in parallel (by 3.1 and 3.0 mmHg, respectively) leaving pressure gradient (delta P) unchanged. APR, as estimated from the clearances of 51Cr-EDTA and lithium, remained unchanged. Urine flow almost doubled. GFR was only modestly reversed (pre-ACZ/ACZ/ACZ+dopamine: 100/77/83%). It is concluded that relieving the afferent vasoconstriction seen after carbonic anhydrase inhibition fails to restore GFR to its control value. This is due to the high flow resistance in the distal nephron segments during the increased tubular flow rates seen after ACZ. The high distal flow resistance causes a parallel change in Pgc and Pprox and thus leaves delta P nearly unchanged. The present study highlights the importance of the distal flow resistance in determining delta P and therefore GFR during conditions where tubular flow rate is increased. PMID- 8203632 TI - An X-ray microanalysis study of Locusta Malpighian tubule cell function using rubidium. AB - Intracellular distributions of Na, K, Mg, Ca, Cl, P, and S were determined in type 1 Malpighian tubule cells of Locusta using X-ray microanalysis. K showed a gradient of increasing concentration from basal to apical surfaces. No other element showed this distribution. Na was below the detection limit. Three types of dark body were present in cytoplasm; one rich in Ca and P and two rich in K and P. Incubation in Rb-Ringer solution resulted in a dramatic fall in cellular K that was not completely replaced by Rb. The distribution of Rb mimicked that of K. Na levels were significantly increased, but the total intracellular monovalent metal concentration was less than in controls. Other elements were little affected. Rb replaced K in dark bodies. Tubules continued to secrete K-rich urine in Rb-Ringer solution even though intracellular [K] was low. Little Rb+ was secreted and Na+ secretion was unchanged. The possible role of dark bodies as a source of secreted K+ is discussed. PMID- 8203633 TI - Intraventricular but not intraparaventricular nucleus metergoline elicits feeding in satiated rats. AB - Previous research has shown that systemic injections of the nonselective serotonin (5-HT) antagonist metergoline (MET) can stimulate feeding in both rats and humans. Five experiments were conducted to determine if this drug would elicit feeding in otherwise satiated rats after direct injections into the brain. In experiment 1, intraventricular infusions of 100 nmol MET produced reliable enhancements of feeding for 1 h compared with control infusions of a 5% tartaric acid (vehicle) solution. In experiment 2, a dose-response study of 0, 50, 100, and 150 nmol MET intraventricularly revealed that both 100 and 150 nmol doses reliably enhanced 1-h feeding, whereas 50 nmol did not. In experiment 3, tests of 90-min locomotor activity and water intake in the absence of food revealed that 100 nmol MET intraventricularly did not modify either behavior compared with vehicle infusions, suggesting a degree of feeding specificity to this effect. In an attempt to determine the site of intraventricular MET effects on feeding, experiment 4 tested 1-h feeding responses after 0, 5, 10, 20, 40, or 60 nmol MET were infused unilaterally into the paraventricular nucleus (PVN) of the hypothalamus. No reliable feeding was induced at any of these drug doses, although injections of 30 nmol norepinephrine (NE) were effective in doubling food intake. Experiment 5 further showed that bilateral infusions of 50 nmol MET in each PVN (total dose, 100 nmol) were ineffective in altering 1-h feeding. This contrasted markedly to the high potency of 15 nmol NE per site (total dose, 30 nmol), which elicited fivefold greater feeding than control infusions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203634 TI - Rat hypothalamic NPY mRNA and brown fat uncoupling protein mRNA after high carbohydrate or high-fat diets. AB - We measured the influence of diet composition on hypothalamic neuropeptide Y (NPY) message and brown fat uncoupling protein (UCP) mRNA using different diets. Sprague-Dawley rats ate ad libitum either chow, a high-carbohydrate (HC), an intermediate-carbohydrate (IHC), a high-fat (HF), or an intermediate-fat (IHF) diet, all with equal protein content (g/kcal). The HF and IHF groups ate less food mass and, except for HC, all groups consumed similar kilocalories during the study. After 1 wk, we killed the animals and extracted total RNA from arcuate nucleus, cortex, and brown adipose tissue (BAT). Arcuate NPY mRNA in the HF group was significantly (P < 0.001) lower than in the HC and chow group. There were no differences between groups in NPY message in cortex or NPY protein in the paraventricular nucleus. BAT UCP message levels were significantly higher (P = 0.001) in the HF group. Thus HF compared with HC and chow diet reduces expression of NPY mRNA in hypothalamic nuclei and increases expression of BAT UCP message. PMID- 8203635 TI - Ventilatory and metabolic effects of repeated hypoxia in conscious newborn rabbits. AB - To estimate posthypoxia depressing effects on newborns, ventilatory and metabolic effects of repeated hypoxia were studied in 1- to 3-day-old (group 1) and 2-wk old (group 2) conscious rabbits. In group 1 (n = 18), ventilation was measured by means of a flow plethysmograph. The barometric method was used in group 2 (n = 21). In an additional 19 pups of group 1 and 17 rabbits of group 2, oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured with an open flow method. In control animals minute ventilation (VE), respiratory rate, tidal volume, VO2, and VCO2 were recorded at 10-min intervals for approximately 100 min in room air. All variables did not change with time. Separate sets of newborns were exposed five times for 10 min to 10% O2 in N2. Each exposure was followed by 10 min of recovery in room air. VE measured during recoveries after hypoxia always returned to normal in group 1. In group 2, the normoxic VE during the last recovery was greater than the first value in hypoxia-treated rabbits (P < 0.05) and greater than the last value in control rabbits (P < 0.02). Although the VE response to hypoxia was not affected by repetitive exposures in group 2, at minute 5 of the fifth exposure the VE response was greater than that during the first trial in group 1 (P < 0.02). Repetitive exposures had no effects on metabolic response to hypoxia in all pups. Results of this study indicate that hypoxia-related central inhibition, if developed during the exposures, is reversed by 10 min of breathing room air in newborns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203636 TI - Effects of acute salt loading on vasopressin mRNA level in the rat brain. AB - To assess the mutual relationship between acute osmotic stimulation and arginine vasopressin (AVP) gene expression, 2 ml/100 g body weight of 0.9 M NaCl was intraperitoneally administered into conscious rats. They were decapitated to collect blood and brain samples before and 15 min and 1, 3, 6, and 9 h after the injection. The total RNA from the hypothalamus or whole brain tissue was used to determine AVP mRNA by Northern blot analyses with a complementary DNA probe. Plasma AVP and osmolality increased rapidly and transiently 15 min and 1 and 3 h after the injection. AVP mRNA was detected in the hypothalamus but not in the brain tissue without hypothalamus under basal and stimulated conditions. Brain AVP mRNA increased 2.2-fold at 3 h and 1.7-fold at 6 h (P < 0.05-0.01). These increases appeared to be due to the appearance of AVP mRNA with the shorter migration in the gel. These results suggest that an acute osmotic challenge increases AVP mRNA with size heterogeneity within the hypothalamo-hypophyseal tract. PMID- 8203637 TI - Increased lymphatic pressure without increased neck vein pressure during intravenous infusions. AB - Postnodal intestinal lymphatic pressure increases during rapid intravenous infusions with Ringer solution in sheep. Part of the lymphatic pressure increase is due to increased venous pressure at the lymphatic outflow (the neck veins). We tested the hypothesis that other factors besides increased neck vein pressure may cause increased lymphatic pressure during intravenous infusions. We placed cannulas into postnodal lymphatic vessels in eight sheep. After the sheep recovered from the surgery, we infused Ringer solution [46 +/- 21 (SD) ml/kg body wt in 30 min] intravenously into the sheep and inflated a balloon in the inferior vena cava. We adjusted the balloon inflation to prevent any increase in neck vein pressure during the infusions. At baseline, the intestinal lymphatic pressure was 15.5 +/- 2.5 cmH2O. During the infusions, lymphatic pressure increased significantly, and for the last 10 min of the infusion period, intestinal lymphatic pressure was 24.0 +/- 6.1 cmH2O. These results are consistent with the hypothesis that factors in addition to increased neck vein pressure may cause increased intestinal lymphatic pressure during rapid intravenous infusions. PMID- 8203638 TI - Effects of renal denervation on postprandial sodium excretion in experimental heart failure. AB - The hormonal, hemodynamic and renal excretory changes after an oral load of sodium were examined in renal-denervated dogs with an arteriovenous (AV) fistula and the syndrome of compensated high-output heart failure. After ingestion of a meal containing 125 meq of sodium, the total postprandial urinary sodium excretion and fractional sodium excretion were approximately twofold higher in the renal-denervated AV fistula dogs, compared with a control group with intact renal nerves (P < 0.05). The postprandial elevations in right atrial pressure, plasma atrial natriuretic factor, and filtered load of sodium were similar in the two groups (P > 0.05). Mean arterial pressure and plasma renin activity remained unchanged from baseline in the two subsets of animals (P > 0.05). In the renal denervated AV fistula dogs, ingestion of a low-salt meal containing 2-3 meq of sodium produced elevations in creatinine clearance and filtered load of sodium of similar magnitude to the high-salt meal. However, the increases in sodium excretion and plasma atrial natriuretic factor were modest and inconsistent. These results demonstrate that the renal nerves play an important modulatory role for postprandial sodium metabolism after a high-salt meal in experimental compensated high-output heart failure. It is suggested that the renal nerves attenuate the expression of postprandial natriuretic mechanisms via a direct tubular mechanism of action. PMID- 8203639 TI - Influence of pregnancy on ANF release from isolated atria. AB - Isolated perfused right atria were prepared from virgin cycling rats and from rats at 7, 14, and 21 days of pregnancy. Intraluminal pressure was raised from the basal control level (atmospheric) to 4, 6, and 10 cmH2O. Basal and stretch induced release of atrial natriuretic factor (ANF) into the perfusate was measured by radioimmunoassay. When atria derived from unmated and from 7-day pregnant rats were distended, mean ANF secretion into the perfusion medium increased by 64 +/- 16 and 89 +/- 31 pg/ml at the highest distending pressure of 10 mmHg. (Mean basal secretion for the two groups was 196 +/- 104 and 181 +/- 63 pg/ml, respectively.) However, at 14 and 21 days, distension failed to elicit any significant increase in ANF release. There was no significant difference between the groups with respect to basal secretion of ANF, nor did pregnancy influence atrial compliance or volume. The slopes of the pressure-volume curves for atria derived from virgin, 7-, 14-, and 21-day-pregnant rats were 0.76 +/- 0.17, 0.623 +/- 0.178, 0.811 +/- 0.177, and 1.050 +/- 0.173, respectively. These results are in agreement with our findings in vivo that plasma ANF levels are elevated at 7 days of pregnancy but that, despite the progressive increase in intravascular volume, they decrease to control levels at 14 and 21 days. Our latest data suggest that this fall is a result of changes in the secretory characteristics of the atrial tissue itself and not necessarily of pregnancy-induced changes in atrial filling. PMID- 8203640 TI - Role of peripheral capsaicin-sensitive neurons and CGRP in central vagally mediated gastroprotective effect of TRH. AB - We investigated in conscious rats the role of capsaicin-sensitive neurons and alpha-calcitonin gene-related peptide (CGRP), the form preferentially expressed in capsaicin sensory neurons, in mediating intracisternal thyrotropin-releasing hormone (TRH) analogue-induced vagal muscarinic gastroprotection against ethanol lesions. The TRH analogue RX-77368 (1.5 ng ic) reduced by 78 and 66% gastric hemorrhagic lesions induced by intragastric intubation of 60 and 80% ethanol, respectively. alpha-CGRP (1 nmol/kg iv) inhibited by 88% gastric lesions induced by 60% ethanol, and this peptide action was blocked by the CGRP antagonist, CGRP (8-37) (128 nmol/kg iv). The protective effect of RX-77368 against 60% ethanol was completely abolished by the CGRP monoclonal antibody 4901 (4.8 mg/kg iv), CGRP-(8-37) (128 nmol/kg iv), and capsaicin pretreatment (125 mg/kg). Gastric lesions induced by 60% ethanol were not altered by the CGRP antagonist or antibody alone but were enhanced by capsaicin pretreatment. These results suggest that the gastroprotection induced by intracisternal TRH analogue involves an interaction between central vagal efferent pathways and splanchnic sensory afferent terminals containing CGRP. PMID- 8203641 TI - Potential adaptations to acute hypoxia: Hct, stress proteins, and set point for temperature regulation. AB - Severe, intermittent hypoxia (hypoxic conditioning, HC) increases survival time during subsequent lethal hypoxia in mice. This protective effect was blocked by naloxone, suggesting an opioid-dependent mechanism. We proposed and evaluated three potential mechanisms of this acute adaptation: 1) increased hematocrit (Hct), 2) protein synthesis, and 3) decreased set point for temperature regulation (set point). Increased hematocrit is a well-studied adaptation to chronic hypoxia and could be acutely initiated by sympathetically mediated splenic contraction. Survival during stress can be prolonged by synthesis of stress proteins. We tested this hypothesis using two protein synthesis inhibitors, anisomycin and cycloheximide. Our third hypothesis is that set point is decreased after HC. A regulated decrease in body temperature would lower oxygen demand during hypoxia. Our studies indicate that hematocrit and protein synthesis are not dominant mechanisms of acute adaptation to hypoxia. However, we have observed a naloxone blockable decrease in set point after HC, supporting a mechanism in which acute adaptation involves an endogenous opioid-dependent decrease in set point. These studies also demonstrate that set point could be a more dominant contributor than body temperature to hypoxic tolerance. PMID- 8203642 TI - Relative contribution of type I and II corticosterone receptors in VMH lesion induced obesity and hyperinsulinemia. AB - Ventromedial hypothalamic (VMH) lesion-induced obesity is accompanied by hyperinsulinemia and hyperphagia, which are dependent upon corticosterone (Cort) for their expression. Whether Cort exerts these actions through its stimulation of type I or II Cort receptor populations is unknown. Therefore, food intake and weight gain were measured in obese adrenalectomized VMH-lesioned rats given continuous infusion of various doses of either a type I-receptor agonist (aldosterone), a type II-receptor agonist (RU-28362), or several combination doses. Similarly, the receptor population responsible for lesion-induced hyperinsulinemia was identified. Type II receptor stimulation restored the hyperphagia, weight gain, and hyperinsulinemia of adrenalectomized VMH-lesioned animals, while type I receptor stimulation blocked their weight loss. PMID- 8203643 TI - Effect of hepatic portal infusion of pyruvate on pancreatic hormone response during exercise. AB - The purpose of the present investigation was to evaluate the effects of a small infusion of pyruvate into the hepatic portal vein on the pancreatic hormone response during exercise (30-min treadmill run; 26 m/min, 0% grade) in adrenodemedullated rats. Resting and exercising rats were infused with either pyruvate (5% solution; 0.016 ml/min) into the portal vein, pyruvate into the jugular vein, or saline into the portal vein. Peripheral and portal blood glucose concentrations were decreased (P < 0.01) similarly in all groups after the exercise period. Peripheral insulin, glucagon, and norepinephrine levels, either at rest or after exercise, were not significantly affected by the infusions. The response of portal pancreatic hormone concentrations to exercise was, however, reduced by the pyruvate infused into the portal and jugular veins for insulin and into the portal vein only for glucagon. The normal increase in peripheral glucagon-insulin molar ratio during exercise was shut down by the infusion of pyruvate into the portal vein but not by the infusion of pyruvate into the jugular vein or by the infusion of saline. These results indicate that a small blood infusion of pyruvate, even in the presence of a decreasing blood glucose level, can attenuate substantially the pancreatic hormone response during exercise in adrenodemedullated rats. PMID- 8203644 TI - Involvement of liver and skeletal muscle in sucrose-induced insulin resistance: dose-response studies. AB - The ability of dietary sucrose to induce insulin resistance independent of changes in body weight is controversial. In the present study male rats were fed a high-starch (ST) diet (starch 68% of total kcal) ad libitum for 2 wk and then were fed equicalorically either the ST diet or a high-sucrose (SU) diet (sucrose 68% of total kcal) for 8 wk. Euglycemic, hyperinsulinemic (0, 1.2, 4.1, 8, 15 mU.kg-1.min-1, n = 6-8/group per dose) clamps were then used to establish dose response relationships for glucose kinetics and metabolism. Body weight (513 +/- 3 g) and composition were similar between groups after the 8-wk dietary period. Glucose infusion rates (GIR; mg.kg-1.min-1) were significantly less in SU (0.9 +/ 5.8 +/- 0.6, 14.8 +/- 1.3, and 18 +/- 1.1) than in ST rats (4.1 +/- 0.9, 12.3 +/ 1.2, 22.6 +/- 1.5, and 25.9 +/- 1.8) at 1.2, 4.1, 8, and 15 mU.kg-1.min-1, respectively. Impaired suppression of endogenous glucose production accounted for 46, 43, 23, and 0% of the reduction in GIR in SU rats at 1.2, 4.1, 8, and 15 mU.kg-1.min-1, respectively. Despite basal hyperinsulinemia (38 +/- 2 microU/ml in SU vs. 26 +/- 2 microU/ml in ST rats), liver phosphoenolpyruvate carboxykinase (PEPCK) activity was 50% higher in SU than in ST rats and remained elevated in SU rats (by 30-40%) at the two lower insulin doses. No skeletal muscle glycogen accumulation occurred in SU rats at any of the insulin doses, and glycogen synthase I activity was significantly lower in SU rats at the two highest insulin doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203645 TI - Administration of 8-OH-DPAT into the midbrain raphe nuclei: effects on medial hypothalamic NE-induced feeding. AB - The 5-hydroxytryptamine (5-HT)1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has been shown to elicit dose-dependent feeding in satiated rats when injected into the midbrain raphe nuclei. Because the feeding-stimulatory effects of this compound are associated with reduced 5-HT release in forebrain, and because recent evidence suggests that medial hypothalamic norepinephrine (NE) and 5-HT may function antagonistically in the control of feeding, the present study sought to determine whether 8-OH-DPAT would enhance feeding induced by infusing NE into the medial hypothalamus. All experiments were conducted using ad libitum fed adult male rats with two indwelling cannulas, one aimed at the paraventricular nucleus (PVN), the other at either the dorsal or median raphe. In the first series of experiments rats received a fixed dose of 8-OH-DPAT (0.8 nmol) microinjected into the dorsal or median raphe, as well as NE (0, 10, 20 nmol) administered into the PVN. In the second series, rats received varying doses of raphe 8-OH-DPAT (0, 0.4, 0.8 nmol) coinjected with a single dose of PVN NE (20 nmol). Results indicated that 8-OH-DPAT and NE both elicited reliable increases in 1-h food intake, although their effects did not interact. In the final series, rats were injected with subthreshold doses of both compounds. While combined injections of 8-OH-DPAT and NE modestly increased feeding compared with saline control, this increase was not significantly greater than intake found after injection of 8-OH-DPAT or NE alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203646 TI - Involvement of 5-HT3 receptors in the initiation of pharyngeal reflex. AB - Activation of peripheral serotonin (5-HT) receptors, classified as 5-HT3, was shown to elicit the pharyngeal reflex in anesthetized rats. Intravenous bolus injection of 5-HT (6.25-50 micrograms/kg) evoked rhythmic bursts in the efferent pharyngeal branch of the vagus nerve in a dose-related manner, whereas afferent superior laryngeal nerve activity was not altered by even a high dose of 5-HT. The pharyngeal branch response was blocked by pretreatment with a selective 5-HT3 receptor antagonist YM060 (1 and 10 micrograms/kg). A 5-HT3-receptor agonist, 2 methyl-5-HT, also produced a rhythmic burst in the pharyngeal branch, and this effect was blocked by YM060. Intrapharyngeal pressure was rhythmically increased by both 5-HT (12.5-50 micrograms/kg) and 2-methyl-5-HT (6.25-50 micrograms/kg) in a dose-related manner. Both of these effects were antagonized by YM060 (10 micrograms/kg). In addition, a neuromuscular blocking agent vecuronium (1 mg/kg iv) completely inhibited the 5-HT-induced increase in pharyngeal pressure. After a bilateral vagotomy was performed below the nodose ganglia, the 5-HT-induced increase in pharyngeal branch activity was abolished, whereas a bilateral sectioning of the superior laryngeal nerve did not alter the 5-HT-induced increase in pharyngeal branch activity. Retrograde tracing with fluorescent dye (fast blue) was used to identify the cell bodies of the pharyngeal branch. Pharyngeal motoneuron cell bodies were distributed along the entire length of the nucleus ambiguus. Our results suggest that exogenous 5-HT-induced increases in pharyngeal branch activity and intrapharyngeal pressure may be initiated by the peripheral 5-HT3-receptors of the vagal nervous system and that this may be a viscerosomatic reflex. PMID- 8203647 TI - Central interleukin-1 receptors contribute to suppression of feeding after acute colitis in the rat. AB - Experimental colitis, induced in rats by intrarectal administration of trinitrobenzenesulfonic acid (TNB), results in a suppression of eating for 3 days. Because interleukin-1 (IL-1) is elevated within 24 h after TNB treatment, and because chronic administration of IL-1 leads to a pattern of anorexia similar to that seen after TNB, we evaluated the role of endogenous IL-1 in the anorexia observed in the TNB model. Human recombinant IL-1 receptor antagonist (rhIL-1ra) was administered chronically via osmotic minipump either peripherally or centrally after TNB treatment. Peripheral delivery of 40 micrograms/h rhIL-1ra significantly attenuated TNB-induced anorexia. However, 24 micrograms/h rhIL-1ra attenuated TNB-induced anorexia only when delivered centrally, not peripherally. These findings implicate central IL-1 receptors in the suppression of eating during acute experimental colitis but leave open a possible involvement of peripheral IL-1 receptors. PMID- 8203648 TI - Angiotensin II overflow from canine skeletal muscle in vivo: importance of plasma angiotensin I. AB - The overflows (i.e., veno-arterial concentration differences multiplied by plasma flow) of angiotensin-(1-10) decapeptide (ANG I) and angiotensin-(1-8) octapeptide (ANG II) from blood-perfused canine gracilis muscle in situ were studied. Special precautions were taken to minimized ex vivo generation and/or degradation of angiotensins in the sampled blood. ANG I was found to be generated in the catheter system supplying the gracilis muscle with arterial blood, but plasma renin activity and ANG II levels were uninfluenced by the catheter system. A positive venoarterial concentration difference over the muscle itself was found for ANG II but not for ANG I under basal conditions. Isoprenaline elicited vasodilatation, reduced ANG I overflow, and tended to increase ANG II overflow, whereas beta-adrenoceptor blockade by propranolol had no effect on these variables. In conclusion, we found no evidence for a local de novo synthesis of ANG II from the gracilis muscle vasculature in vivo. The net overflow of ANG II was most likely caused by local conversion in the tissue of ANG I artifactually generated in the arterial catheter system. beta-Adrenoceptor stimulation enhanced the local conversion of ANG I to ANG II, probably by exposing a greater endothelial surface containing angiotensin-converting enzyme activity. PMID- 8203649 TI - Interleukin-8 induces fever by a prostaglandin-independent mechanism. AB - We have studied the mechanism by which interleukin-8 (IL-8) induces fever in rats. Intracerebroventricular injections of IL-8 (5.5-50 ng) evoked dose dependent increases in body temperature, which reached a plateau 5 h after injection, i.e., later than intracerebroventricular interleukin-1 beta (IL-1 beta; 2 h). The pyrogenic activity of IL-8 was not due to contamination with lipopolysaccharide (LPS) because preincubation of IL-8 with a specific antibody or boiling the IL-8 for 30 min abolished its activity but not that of LPS; also, IL-8 but not LPS induced fever in LPS-tolerant rats. Indomethacin significantly reduced the pyrogenic effects of intracerebroventricular injections of LPS and IL 1 beta but not responses to IL-8, suggesting that pyrogenic responses to IL-8 were mediated independently of prostaglandins. In contrast, dexamethasone markedly attenuated pyrogenic responses to IL-8 and IL-1 beta. These data suggest that inhibition of IL-8 by glucocorticoids contributes to the antipyretic effects of these drugs in fevers resistant to cyclooxygenase inhibitors. PMID- 8203650 TI - Dissociation between plasma and brain amino acid profiles and short-term food intake in the rat. AB - The relationship between plasma and brain amino acids and short-term food intake after administration of albumin, or its constituent amino acids, was examined. Rats given protein (0.85 g chicken egg albumin) or an amino acid mixture patterned after egg albumin reduced their food intake during 1 h of feeding beginning 30 min after gavage. Similarly, when given separately, the essential (EAA) and nonessential amino acid (NEAA) fractions of egg albumin caused comparable decreases in food intake. As the dose increased from 0.5 to 1.5 g the duration of anorexia prolonged to 12 h. Little change occurred in plasma amino acids at 30 and 60 min after albumin at 0.85 g, although many increased by 25-50% at 60 min after 1.5 g. Marked changes in plasma occurred after gavage with the total mixture of constituent free amino acids and after either EAA or NEAA fractions. Brain amino acid concentrations were little affected by albumin and did not show consistent changes after the amino acid treatments. Thus the reductions in food intake after ingestion of albumin or of its constituent amino acids were not predicted from the resulting changes in either plasma or brain concentrations of amino acids. PMID- 8203651 TI - Role of hypothalamic neuropeptide Y gene expression in body weight regulation. AB - Hypothalamic neuropeptide Y (NPY) may be involved in the hyperphagia that follows food deprivation associated with significant weight loss. However, it is unclear whether NPY is involved in body weight regulation under more physiological circumstances. Consequently, we measured body weight, food intake, arcuate nucleus (ARC) NPY mRNA, serum glucose, and insulin in male Wistar rats after 48 h of food deprivation and various refeeding protocols. Food deprivation produced a twofold increase in NPY mRNA, whereas 3 days of ad libitum refeeding returned body weight and NPY mRNA to control. If hyperphagia was prevented for 5 days during refeeding, then neither body weight nor NPY mRNA normalized. There were strong negative correlations between ARC NPY mRNA and both loss of body weight and serum insulin levels. These data suggest that hypothalamic NPY gene expression plays a role in control of body weight under physiological conditions. The data further suggest that NPY mRNA may be decreased by peripheral insulin levels. PMID- 8203652 TI - Brief mesenteric ischemia increases PGE2, but not PGI2, in intestinal lymph of cats. AB - Mesenteric ischemia of short duration (5-10 min) can stimulate A delta- and C fiber afferent nerve endings in the viscera to reflexly activate the cardiovascular system. The mechanism of activation of abdominal visceral afferents is probably multifactorial and may involve prostaglandins (PGs), which have been shown to directly stimulate and/or sensitive visceral afferents when administered exogenously. We hypothesized that brief visceral ischemia is accompanied by release of PGI2 and PGE2 into the interstitium, where these cyclooxygenase products could stimulate or sensitize visceral afferent nerve endings. Accordingly, we measured immunoreactive PGE2 (iPGE2) and 6-keto-PGF1 alpha (i6-keto-PGF1 alpha), the stable metabolite of PGI2, in lymph draining the ischemic viscera as well as in portal venous blood. An intestinal lymph duct distal to the lymph node was cannulated in pentobarbital sodium-anesthetized cats. Lymph and plasma iPGE2 and i6-keto-PGF1 alpha concentrations were measured by radioimmunoassay before, during, and immediately after a 5- to 10-min occlusion of the descending aorta. The i6-keto-PGF1 alpha concentration increased significantly (P < 0.001) in portal venous plasma (61 +/- 12 to 107 +/- 18 pg/0.1 ml; n = 14) but not in lymph (148 +/- 30 to 159 +/- 24 pg/0.1 ml; n = 16). In contrast, iPGE2 concentration was significantly (P < 0.01) elevated in both venous plasma (156 +/- 16 to 207 +/- 26 pg/0.1 ml; n = 19) and lymph (520 +/- 48 to 590 +/- 52 pg/0.1 ml; n = 20).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203653 TI - Quantitative modeling and biology: the multivariate approach. AB - Even though elegant examples of mathematical modeling of biological problems exist, such approaches still remain outside the domain of most biologists. It is proposed that, for a wider and more systematic use of mathematical models in biology, the soft modeling approaches, which are applicable to phenomena with a limited level of definition, should be investigated and preferred. In particular, multivariate data analysis (MDA) is indicated as an important tool toward fulfilling this goal. This paper reviews the general principles of MDA and examines in detail principal component analysis and cluster analysis, which are two of the most important MDA techniques. A number of applications to real biological problems are presented. These examples show how the construction of classifications corresponds to the generation of new knowledge and new concepts, which are hierarchically on a higher level than the initial information. This new form of knowledge is obtained without superimposing a priori theories on the data. It is demonstrated how the MDA can lead to the identification of biological systems; also shown is their ability to describe multiple scale phenomena, a typical feature of biological systems. Moreover, the multivariate analyses provide new descriptors for a given biological system; these descriptors are quantitative, thus allowing the system to be described in a "metric space," where it then becomes possible to use any other mathematical tool. PMID- 8203654 TI - Use of sinoaortic denervation to study the role of baroreceptors in cardiovascular regulation. AB - To assess the role of arterial baroreceptors in cardiovascular regulation, many studies have used rats in which baroreceptor afferents have been surgically destroyed. However, interpretation of studies using sinoaortic-denervated (SAD) rats is complicated by variability in the extent of baroreceptor denervation. We have compared cardiovascular regulation in rats with total sinoaortic cardiovascular regulation in rats with total sinoaortic denervation, as assessed by the abolition of reflex changes in heart rate (HR) to increases and decreases in arterial pressure (AP), with rats that underwent the same denervation procedure but still had residual (although markedly blunted) reflex changes in HR to changes in AP. In totally SAD rats, the lability of AP was greatly exaggerated compared with sham-denervated rats, although the average AP was equivalent. In contrast, partially SAD rats had elevated AP, and although AP was more labile than in sham-denervated rats, it was less labile than in totally SAD rats. In addition, cardiovascular responses elicited by elimination of neural activity in the nucleus tractus solitarius (NTS) were qualitatively different between the two groups of rats; destruction of the NTS increased AP similarly in partially SAD rats and sham-denervated rats, whereas this treatment did not alter AP in totally SAD rats. Thus there are marked differences in SAD rats with no residual arterial baroreceptor reflex function compared with SAD rats with even a small degree of residual baroreceptor reflex function. These studies highlight the importance of carefully characterizing SAD rats used in studying the role of the baroreceptor reflex in cardiovascular regulation. PMID- 8203655 TI - A novel role for the nitric oxide-cGMP signaling pathway: the control of epithelial function in Drosophila. AB - The nitric oxide (NO) signaling pathway plays major roles in the vertebrate vascular, nervous, and immune systems. Here we present evidence that all the elements in the NO pathway are present in, and act to control epithelial fluid secretion by, the Malpighian tubules of an insect, Drosophila melanogaster. This finding will allow both a physiological and a molecular genetic dissection of the NO pathway in the same tissue. PMID- 8203656 TI - Incest and the idealized self: adaptations to childhood sexual abuse. PMID- 8203657 TI - The consultant's role in resolving impasses in therapeutic relationships. PMID- 8203658 TI - Empathic character analysis. PMID- 8203659 TI - Radical self-psychology. PMID- 8203660 TI - Exploratory thoughts on wisdom, intimacy, and analytic relatedness. PMID- 8203661 TI - In search of ordinariness: the dissolution of false pride. PMID- 8203662 TI - American institute for psychoanalysis. The president and Prozac. PMID- 8203663 TI - The resurgence of tuberculosis in New York City: a mixed hierarchically and spatially diffused epidemic. AB - For New York City from 1978 to 1990, plotting the 3-year running averages of citywide new tuberculosis cases against the middle year yielded an S-shaped curve, with the inflection point at 1983 between early slow and late rapid rise. The inflection in the S curve appears to be associated with hierarchical establishment of secondary epicenters, and the phase of rapid rise in new cases seems to be associated with spatial diffusion from both the primary and secondary epicenters. PMID- 8203664 TI - Temporal trends in the socioeconomic gradient for breast cancer mortality among US women. AB - Temporal trends in breast cancer mortality among US women were examined for 1969 through 1989 by age, race, and county-level socioeconomic status (SES). The mortality ratio for high- relative to low-SES counties declined significantly among women 25 to 44, 45 to 64, and more than 65 years of age, respectively, from 1.13 to 0.96, 1.32 to 1.19, and 1.48 to 1.26. The narrowing of mortality occurred among Whites and, to a lesser extent, Blacks. A relative increase in either breast cancer incidence among women in lower SES counties or improved survival among women in higher SES counties (reflecting greater use of screening and treatment) could account for this relative worsening of breast cancer mortality among lower SES women in lower SES counties. PMID- 8203665 TI - Racial differences in cervical cancer mortality in Chicago. AB - Racial differences in cervical cancer mortality in Chicago were examined. Age adjusted mortality in Blacks (10.0/100,000) was over twice the rate found in Whites (4.6/100,000). Age-specific rates also showed significant excess mortality among Blacks. After stratification by a group-level defined poverty indicator, the race differential in age-adjusted rates remained significant. The race differential in age-specific rates diminished in the group with more than 30% living below the national poverty level, in contrast to the group with 30% or fewer living below the national poverty level, in whom race differences were more marked. Methodological issues concerning hysterectomy prevalence, Hispanic ethnicity, and social class must be considered with respect to interpretation of these findings. PMID- 8203666 TI - Access to family planning services and health insurance among low-income women in Arizona. AB - This paper uses 1984 and 1989 Arizona survey data to explore the importance of insurance coverage for access to family planning services. In Arizona, Medicaid was provided through the Arizona Health Care Cost Containment System, a managed care model. Family planning was not provided in 1984 but had been added by 1989. Low-income women were 2.3 times more likely to receive services in 1989 than in 1984. Women in the system were 60% more likely to have received services. To improve access, health reform proposals should explicitly include family planning in managed care benefits packages. PMID- 8203667 TI - Sex bias in the management of coronary artery disease in Quebec. AB - This study tests the hypothesis that, given the absence of financial barriers to major coronary procedures in Quebec, women are as likely as men to undergo such procedures. The use of coronary procedures in 33,940 patients with ischemic heart disease, admitted during 1 year to 78 Quebec hospitals, was analyzed. The male-to female age- and severity-adjusted odds ratios for the use of these procedures were 1.47 for diagnostic procedures, 1.38 for therapeutic procedures, and 1.26 for diagnostic and therapeutic procedures. These results suggest that differences in the use of coronary procedures by sex are influenced by factors other than financial accessibility. PMID- 8203668 TI - Health insurance coverage among persons with AIDS: results from a multistate surveillance project. AB - To determine factors associated with health insurance coverage among persons with acquired immunodeficiency syndrome (AIDS), we interviewed 1958 persons 18 years of age or older who were reported to have AIDS in 11 states and cities. Overall, 25% had no insurance, 55% had public insurance, and 20% had private insurance. Factors associated with lack of insurance varied by current employment status. Employed persons with an annual household income of less than $10,000 were 3.6 times more likely to lack insurance than employed persons with a higher income. Unemployed persons diagnosed with AIDS for less than 1 year were two times more likely to lack health insurance than unemployed persons diagnosed for a longer time. Making insurance available to persons identified as most likely to lack insurance should improve access to care for persons with AIDS. PMID- 8203669 TI - The reliability of racial classifications in hospital discharge abstract data. AB - Many studies demonstrating an association between race and the use of medical services have used hospital discharge abstract data. The quality of the measures of race in such data sources has heretofore been unexplored. Hospital discharge abstract data from New York State were used to identify 767 cardiac patients who had been admitted to a hospital twice. Racial classifications during the two admissions were concordant 93.7% of the time. Kappa was .89 for Blacks, .72 for Whites, and .43 for all other racial groups. Evidence suggests that the misclassification of race in hospital discharge abstract data is nondifferential; racial discrepancies in access to medical services are thus probably even greater than those previously reported. PMID- 8203670 TI - The trials of Hanna Porn: the campaign to abolish midwifery in Massachusetts. AB - The case of Hanna Porn affords an opportunity to examine how the laws that led to the abolition of midwifery in Massachusetts evolved and were applied to the midwife whose case set the state legal precedent. Mrs Porn served primarily a Finnish-Swedish clientele of wives of laborers. The outcomes of the births she attended appear to have been positive, and she maintained a neonatal mortality rate of less than half that of local physicians. She also repeatedly defied court orders to stop practicing. Her case exemplifies the efforts that occurred nationally to abolish midwifery in the United States. PMID- 8203671 TI - A homeless teen pregnancy project: an intensive team case management model. PMID- 8203672 TI - A population-based screening mammography program in Saskatchewan. PMID- 8203673 TI - Clarifying the legal definition of "undocumented aliens". PMID- 8203674 TI - The protective effect of nonoxynol-9 against HIV infection. PMID- 8203675 TI - Access to comprehensive health services is fundamental. PMID- 8203676 TI - Smoking and drug interactions. PMID- 8203677 TI - Vitamin supplement use and mortality. 1. Study that found no relationship is challenged. PMID- 8203678 TI - Formulating public health policy: the case of AIDS. PMID- 8203679 TI - The urgent need for a vaginal microbicide in the prevention of HIV transmission. PMID- 8203680 TI - Elucidating the relationships between race, socioeconomic status, and health. PMID- 8203681 TI - Why a rising tide doesn't lift all the boats: Medicaid and medical care for children. PMID- 8203682 TI - AIDS prevention and cultural sensitivity: are they compatible? PMID- 8203683 TI - Rationing or rationalizing children's medical care: comparison of a Medicaid HMO with fee-for-service care. AB - OBJECTIVES: This paper examines how medical care obtained by children enrolled in a Medicaid health maintenance organization (HMO) differs from that obtained by similar children who receive care from fee-for-service Medicaid providers. METHODS: In a randomized trial, some Medicaid households were assigned to remain in a traditional fee-for-service arrangement and others were randomly selected to join a Medicaid prepaid plan (an HMO). Participating households recorded data on children's health status and use of medical care. RESULTS: The prepaid plan members and the fee-for-service recipients received equivalent numbers of checkup visits, but the children in the prepaid plan made significantly fewer acute care visits. This plan appeared to target its services to children with the greatest health care needs. However, the content of health visits in the two systems did not differ, nor did prepaid and fee-for-service enrollees use the emergency room differently. CONCLUSIONS: It is possible to design a Medicaid HMO that achieves financial savings without reducing services to the most vulnerable patients. However, these findings alone do not provide a basis for widespread policy change in the direction of Medicaid HMOs. Further research is needed to establish whether the children treated in the HMO differed in health outcomes from those treated by fee-for-service care. PMID- 8203684 TI - The role of state health departments in formulating policy: a survey on the case of AIDS. AB - OBJECTIVES: Public health departments have been criticized for not being on the cutting edge of health policy formation in the United States and, in particular, for being ineffective in dealing with acquired immunodeficiency syndrome (AIDS). This study examines the attitudes and influence of public health officials on this problem. METHODS: A survey of state health department officials was supplemented by surveys of state legislature health committee chairs and hospital association directors, as well as by interviews with key AIDS policymakers and observers in six states. RESULTS: Both in their own eyes and in the eyes of legislative leaders and hospital association officials, public health officials were considered to be the principal initiators of public policy on AIDS. CONCLUSIONS: Contrary to the Institute of Medicine's 1988 report, state health departments are leaders in the fight against AIDS at the state level. Moreover, we argue that public health departments should be judged on how effectively they perform functions for which they have primary legal responsibilities, not for other roles for which they have been given neither responsibility nor resources. PMID- 8203685 TI - The use of nonoxynol-9 for protection against cervical gonorrhea. AB - OBJECTIVES: Although condoms are the best defense against sexually transmitted disease, little is known about the effectiveness of female-controlled methods containing nonoxynol-9 as backup protection when condoms are not being used. METHODS: To assess the extent to which nonoxynol-9 protects women against gonorrhea, a cohort of 303 female sex workers (prostitutes) in Yaounde, Cameroon, were asked to use condoms and suppositories containing nonoxynol-9 at every sexual encounter and to record daily sexual activity and use of condoms and suppositories on coital logs that were reviewed monthly. Evidence of gonorrheal infection was based on a positive gonorrhea culture. Stratified analysis and proportional hazards regression were used to estimate rate ratios. RESULTS: Forty one women enrolled in the study were excluded from the current analysis. The estimated incidence of gonorrhea was 6.2 infections per 100 person-months of observation. Incidence rate ratios estimated from proportional hazards regression models controlling for condom use showed that using nonoxynol-9 during acts not protected by condoms reduced the risk of infection. CONCLUSIONS: Although the protective effect of condoms against sexually transmitted disease is greater than that afforded by nonoxynol-9, using nonoxynol-9 when condoms are not used is a far better strategy in gonorrhea prevention than using no method at all. PMID- 8203686 TI - Are bisexually identified men in San Francisco a common vector for spreading HIV infection to women? AB - OBJECTIVES: This article examines sexual risk taking among self-identified bisexual men in San Francisco and whether risk reduction has occurred, with respect to both homosexual and heterosexual behaviors, among human immunodeficiency virus (HIV) antibody-positive and HIV antibody-negative men. It also examines psychosocial correlates of unprotected anal and vaginal intercourse. METHODS: The participants were members of a population-based longitudinal cohort of 1034 single men aged 25 through 54 years recruited from the 19 census tracts in San Francisco that had the greatest prevalence of the acquired immunodeficiency syndrome in 1984. Of the total sample, 140 subjects initially identified themselves as bisexual; 85% of these men remained in the study. RESULTS: The participants reported dramatic reductions in sexual risk taking. Prevalences of unprotected anal sex with men were similar among HIV positive bisexual men (89% in 1984-1985 and 18% in 1988-1989) and those who were HIV negative (65% and 20%). The prevalence of unprotected vaginal sex was much lower for HIV-positive men (16% in 1984-1985 and 2% in 1988-1989) than for HIV negative men (35% and 20%). Unprotected intercourse was associated primarily with situational and interpersonal factors. CONCLUSIONS: Striking reductions in risk behaviors were reported. This subgroup of single, bisexually identified men appears unlikely to be a common vector for spreading HIV infection to women. PMID- 8203687 TI - Correlates of needle sharing among injection drug users. AB - OBJECTIVES: The sharing of contaminated injection equipment is the primary mode of human immunodeficiency virus (HIV) transmission for injection drug users. This study examined demographic factors, life events, and drug use practices that are potential risk factors for sharing injection equipment. METHODS: Between February 1988 and March 1989, 2921 active injection drug users were interviewed and questioned about their backgrounds, life-styles, and patterns of injection drug use. RESULTS: Of 2524 participants who reported injecting drugs within the 6 months prior to study enrollment, 70.4% reported recent needle sharing. A multivariate analysis found needle sharing to be more frequent among those with a history of arrest and lower socioeconomic status, even after accounting for other demographic and drug use variables. In addition, recent needle sharing was higher in male homosexual or bisexual men than in their heterosexual counterparts. CONCLUSIONS: These data suggest that injection drug users have an economic motive to share needles and that the availability of free and legal needles may reduce levels of needle sharing. PMID- 8203688 TI - The effects of early education intervention on maternal employment, public assistance, and health insurance: the infant health and development program. AB - OBJECTIVES: The purpose of this study was to test whether early education intervention influences maternal employment, education, fertility, and receipt of public assistance and health insurance. METHODS: The Infant Health and Development Program is a randomized trial of the efficacy of early education on the outcomes of 985 low-birthweight, premature children. Families in eight sites received either pediatric follow-up and referral (follow-up only group) or pediatric services plus early intervention services (intervention group) for the first 3 years of the child's life. RESULTS: Mothers in the intervention group were employed more months and returned to the work force earlier than those in the follow-up only group. Fertility and education were not associated with treatment. Mothers who had some college education received more months of public assistance in the intervention group compared with the follow-up only group. Mothers who were employed received more public assistance and public health insurance in the intervention group compared with the follow-up only group, when maternal employment was controlled. CONCLUSIONS: Findings are discussed in terms of the recent emphasis on two-generational programs directed to providing health, welfare, and child care services to young children and their families. PMID- 8203689 TI - The size of mortality differences associated with educational level in nine industrialized countries. AB - OBJECTIVES: This study addresses the question of whether inequalities in premature mortality related to educational level differ among countries. METHODS: Data on mortality by educational level were obtained from longitudinal studies from nine industrialized countries. The data referred to men between 35 and 64 years of age. The follow-up periods occurred between 1970 and 1982. The size of mortality differences associated with educational level was measured by means of two inequality indices, both based on Poisson regression analysis. RESULTS: Inequalities in mortality are relatively small in the Netherlands, Sweden, Denmark, and Norway and about two times as large in the United States, France, and Italy. Finland and England and Wales occupy intermediate positions. The large inequalities in mortality in the United States and France can be attributed in part to large inequalities in education in these countries. CONCLUSIONS: The international pattern found in this study was also observed in a comparison that used occupation as the socioeconomic indicator. Differences between countries in levels of inequality in mortality may be partially explained by the countries' different levels of egalitarian social and economic policies. PMID- 8203690 TI - Why did black life expectancy decline from 1984 through 1989 in the United States? AB - OBJECTIVES: The objective of this study was to partition the change in US life expectancy into those major causes of death and age groups that contributed most to the decline in life expectancy for Black males and females and to the increase in life expectancy for White males and females in the period from 1984 through 1989. METHODS: By means of a life table partitioning technique, the positive and negative contributions of age and cause of death to changes in life expectancy were estimated. RESULTS: Causes contributing most to the decrease in life expectancy for Black males included human immunodeficiency virus (HIV) infection (< 5 and 20-69 years of age) and homicide (1-4 and 10-34 years of age); for Black females the causes included HIV infection (< 5 and 20-59 years of age) and cancer (65-79 and > or = 85 years of age). CONCLUSIONS: Mortality trends between the two major race groups in the United States diverged sharply, and without precedent, during the late 1980s. A description of these trends in terms of contributions to change in life expectancy may help us better analyze and interpret changes in the health of these groups and may contribute to a better allocation of resources for research, education, and public health programs. PMID- 8203691 TI - The effects of occupational class transitions on hypertension: racial disparities among working-age men. AB - OBJECTIVES: This study was undertaken to examine how the interaction between occupational class transitions and race affects the incidence of hypertension. METHODS: A cohort of 1982 men (183 Black), ages 25 to 55, received a baseline medical exam between 1971 and 1975 and a follow-up between 1982 and 1984. Logistic regressions were estimated for hypertension at follow-up controlling for hypertension at baseline, other risk factors associated with blood pressure, and interaction terms identifying specific occupational class transitions among Blacks and Whites. The occupational class matrix was based largely on scores of US Census Bureau occupations from the Dictionary of Occupational Titles. RESULTS: Relative to Whites who remained in professional and technical jobs between baseline and follow-up, Blacks and Whites who remained in lower occupational classes or made specific transitions--notably into the lowest class--had significantly higher incidence rates of hypertension. These differences were greater among Blacks, who are also more concentrated in and less likely to move upward from the lower end of the occupational class matrix. CONCLUSIONS: Widening racial disparities in high blood pressure over the period of study may be partly attributable to characteristics associated with occupational class position and dynamics. PMID- 8203692 TI - Diagnoses, symptoms, and attribution of symptoms among black and white inpatients admitted for coronary heart disease. AB - OBJECTIVES: This study examined health care-seeking behaviors to elucidate factors that contribute to differences in patterns of coronary heart disease between African Americans and Whites. The prevalence of diagnosed coronary heart disease, patients' perceptions of symptoms and attribution of symptoms, and predictors of painful symptoms and attribution of cardiac symptoms were examined. METHODS: The study involved 2416 patients admitted with diagnoses of coronary artery disease, ischemic heart disease, or myocardial infarction or to rule out myocardial infarction. Structured interview questions were used to obtain demographic information, symptoms precipitating admission, and patients' attribution of their symptoms. Discharge diagnoses were obtained from hospital records. RESULTS: Acute myocardial infarction, unstable angina, nonacute ischemic heart disease, and atherosclerosis were more frequent in White patients. For Blacks, the odds of reporting painful symptoms were only 64% of the odds found for Whites when other factors were controlled, and the odds of attributing symptoms to cardiac origins were almost 50% lower for Blacks than for Whites. CONCLUSIONS: The tendency of Blacks to report fewer painful symptoms and to attribute their symptoms to noncardiac origins may contribute to differences in care-seeking and in medical management of heart disease in Blacks. PMID- 8203693 TI - Do blacks and whites differ in their use of health care for symptoms of coronary heart disease? AB - OBJECTIVES: The purpose of this study was to identify the role of race in seeking and receipt of care for symptoms of coronary heart disease. METHODS: Data on medical care, sociodemographic characteristics, symptoms, risk factors, income, and insurance were collected in a telephone interview for a random sample of 2030 Black and White adults in inner-city Boston. Rates of care-seeking for symptoms, amounts of delay in seeking care, and rates of receipt of care were compared for Blacks and Whites after adjustment for other characteristics. RESULTS: Before and after adjustment for other factors, Blacks and Whites were equally likely to seek care. Average delay time was shorter for Blacks, particularly Black women. With the exception of a lower rate of referral to cardiologists among Blacks, receipt of care was similar for Blacks and Whites who sought medical attention for symptoms. CONCLUSIONS: In an urban population of Blacks and Whites who were similar in socioeconomic status and access to medical care, there were few racial differences in coronary heart disease-related care patterns. PMID- 8203694 TI - Acute chest pain in African Americans: factors in the delay in seeking emergency care. AB - OBJECTIVES: African Americans have been shown to have longer delay times than the majority population in seeking care for acute cardiac problems. The purpose of this study was to determine whether socioeconomic factors affect delay times. METHODS: Structured interviews were administered to 254 African Americans admitted to a public hospital and 194 African Americans admitted to a private hospital for suspected acute myocardial infarction. RESULTS: Patient characteristics found by multiple regression analysis to affect decision-making and travel time for care-seeking were structural access to care, persistence of symptoms, degree of incapacitation, consultation with a layperson, consultation with medical professionals, and mode of transportation. CONCLUSIONS: Within-group differences were found to be related to socioeconomic status. Strategies to increase knowledge about heart attack symptoms, improve access to care, and improve the socioeconomic status of at-risk African Americans are indicated. PMID- 8203695 TI - Behavioral risk factors: a comparison of Latinos and non-Latino whites in San Francisco. AB - OBJECTIVES: The purpose of the study was to evaluate differences between Latino and non-Latino White adults in health-related behavioral risk factors. METHODS: Telephone interviews were conducted with 652 Latinos and 584 non-Latino Whites in San Francisco selected by random-digit dialing. RESULTS: Latino men and women, compared with their non-Latino White counterparts, were less likely to have consumed any alcoholic beverage in the previous month (59% and 29% vs 77% and 75%, respectively), consumed fewer drinks per week (6.6 and 3.0 vs 8.9 and 5.1, respectively), and were more likely to be sedentary (40% and 46% vs 17% and 23%). Latina women were less likely than non-Latina Whites to smoke cigarettes (8% vs 29%), to have ever had a Pap smear (76% vs 93%), and to have ever had a clinical breast examination (81% vs 96%). Multivariate analyses adjusting for sex, age, education, and employment confirmed univariate findings. CONCLUSIONS: Behavioral risk factor profiles by ethnicity help emphasize priorities of health promotion programs for a community. Latino needs include maintenance of limited consumption of alcohol and cigarettes, promotion of regular physical activity, and increasing use of low-cost cervical and breast cancer screening tests. PMID- 8203696 TI - Social influences on the sexual behavior of youth at risk for HIV exposure. AB - OBJECTIVES: Adolescents are increasingly at risk for infection with human immunodeficiency virus (HIV) and other sexually transmitted diseases, especially in poor urban minority communities. To aid the design of interventions in these communities, this study investigated the role of knowledge, attitudes, perceived parental monitoring, and peer behavior in the onset and progression of sexual behavior in children at risk for exposure to HIV. METHODS: A computerized personal interview was administered to 300 African-American 9- to 15-year-old children living in six public housing developments in a large US city. RESULTS: Although children's knowledge about the hazards of sex increased with age, their sexual activity also increased (from 12% sexually experienced at 9 years of age to more than 80% experienced at 15 years of age). Parental monitoring appeared able to influence sexual activity. However, the perceived behavior of friends was associated with the rate at which sexual activity progressed with age and the degree to which condom use was maintained with age. CONCLUSIONS: The early onset and prevalence of sexual behavior and the importance of peer group influence call for early interventions that simultaneously influence the parents and peers in children's social networks. PMID- 8203697 TI - The adequacy of prenatal care and incidence of low birthweight among the poor in Washington State and British Columbia. AB - OBJECTIVES: The purpose of this study was to examine differences in adequacy of prenatal care and incidence of low birthweight between low-income women with Medicaid in Washington State and low-income women with Canadian provincial health insurance in British Columbia. METHODS: A population-based cross-sectional study was done by using linked birth certificates and claims data. RESULTS: Overall, the adjusted odds ratio for inadequate prenatal care in Washington (comparing women with Medicaid with those with private insurance) was 3.2. However, the risk varied by time of Medicaid enrollment relative to pregnancy (2.0, 1.0, 2.7, 6.3; for women who enrolled prior to pregnancy, during the first trimester, during the second trimester, or during the third trimester, respectively). In British Columbia, the adjusted odds ratio for inadequate care (comparing women receiving a health premium subsidy with those receiving no subsidy) was 1.5 for women receiving a 100% subsidy and 1.2 for women receiving a 95% subsidy. The risk for low birthweight followed a similar trend in both regions, but there was no association with enrollment period in Washington. CONCLUSIONS: Overall, the risk for inadequate prenatal care among poor women was much greater in Washington than in British Columbia. Most of the difference was due to Washington women's delayed enrollment in Medicaid. In both regions, the poor were at similar risk for low birthweight relative to their more affluent counterparts. PMID- 8203698 TI - Smoking and mortality among residents of a California retirement community. AB - Smoking cessation decreases mortality among the elderly. Participants in the Leisure World Cohort Study initiated in 1981 were followed until death or January 1, 1991. The 8869 women and 4999 men (median age = 73 years at initial survey) contributed 105,952 person-years of follow-up; 4002 had died. All-cause mortality rates were highest among current smokers; compared with never smokers the age adjusted relative risks (and 95% confidence intervals) were 1.67 (1.46, 1.92) for women and 1.95 (1.66, 2.30) for men. Current smokers had increased risks of coronary heart disease, other cardiovascular disease, and cancer. Risk of death from smoking-related cancers continued to be high among former smokers, although lower than the risk among current smokers. Relative risks of mortality from cancer and cardiovascular disease increased with the number of cigarettes smoked per day and with a decreasing number of years since cessation of smoking. PMID- 8203699 TI - The utility of HMO data for the surveillance of chronic diseases. AB - In an area served by a single medical center that operates as both health maintenance organization (HMO) and fee-for-service clinic, we reviewed existing computerized medical records to determine the prevalence of 11 diseases. Standardized medical care utilization prevalence ratios, comparing the annual prevalences in the two groups, varied from 1.38 for rheumatoid arthritis to 0.60 for liver cirrhosis. Unless supplemented by data from hospitals, physicians, and other sources, HMO data may result in invalid estimates of the prevalence of chronic disease. PMID- 8203700 TI - Popular films do not reflect current tobacco use. AB - This study examined trends in tobacco use in a random sample of 2 of the 20 top grossing US films each year from 1960 through 1990 (62 films). The overall rate of tobacco use did not change. Films continue to portray smokers as successful, attractive White males. Smoking groups became larger, smoking alone declined, hostility and stress reduction were increasingly associated with smoking, and smoking by minor characters increased. Although smoking among elite characters fell, it remained nearly three times as prevalent as in actual population data during the 3 decades. Events involving young people more than doubled. Films do not accurately represent smoking in the United States. PMID- 8203701 TI - Short report: imported mosquito: an uninvited guest. AB - Recently, the trend in the number of people traveling from the tropics to malaria free areas has tremendously increased and this is paralleled by the number of imported malaria cases. Imported infected mosquitoes transmitting the infection to persons living or working nearby international airports have been reported. The possibility that mosquitoes may also reach areas far away from the landing area in the baggage of international travelers is indicated by two cases that are reported here. Malaria should be investigated in any case of unexplained fever even if no apparent risk factor for imported malaria is present, regardless of the distance from international airports. PMID- 8203702 TI - Geographic information system in malaria surveillance: mosquito breeding and imported cases in Israel, 1992. AB - Although a significant resurgence of malaria in Israel is unlikely at present, the risk for a localized outbreak of malaria cases due to infection of local anopheline mosquitoes by imported cases does exist. A national computerized surveillance system of breeding sites of Anopheles mosquitoes and imported malaria cases was established in 1992 using a geographic information system (GIS). Distances between population centers and breeding sites were calculated, and maps associating epidemiologic and entomologic data were generated. Risk of malaria transmission was assessed with consideration of vectorial capacity and flight range of each Anopheles species. The GIS-based surveillance system ensures that if a localized outbreak does occur, it will be associated rapidly with a likely breeding site, a specific Anopheles vector, and a probable human source, so that prompt control measures can be most efficiently targeted. This cost effective GIS-based surveillance system can be expanded and adapted for countries with indigenous malaria transmission. PMID- 8203703 TI - Didelphis marsupialis, an important reservoir of Trypanosoma (Schizotrypanum) cruzi and Leishmania (Leishmania) chagasi in Colombia. AB - The role of Didelphis marsupialis as a reservoir of zoonotic hemoflagellates was examined in two ecologically distinct settings in Colombia. While 72% (12 of 18) of the opossums collected in the tropical rain forest harbored Trypanosoma cruzi, other mammals in the area had lower infection rates: 1.3% (Proechymis semispinosus [spiny rat]; 13% Tylomys mirae [climbing rat]; and 6% Rattus rattus). Trypanosoma cruzi isolates from D. marsupialis were similar to zymodeme 1 (Z1), and two of four phenotypes were shared with Tylomys mirae, which is also predominantly arboreal. Terrestrial (P. semispinosus) and peridomestic (R. rattus) animals were infected with Z3 or other Z1 phenotypes, respectively. Schizodeme analysis showed polymorphisms among isolates from mammals, reflecting diverse modes of transmission, and a complex epidemiologic situation. Despite the lower infection rate of the opossum (14%) found in our study in the tropical dry forest as compared with the tropical wet forest, Chagas' disease has been reported only in the former area. This suggests that the lack of alternative blood sources for triatomines of the tropical dry forest, where mammals are less abundant than in the wet forest, may increase the risk of human infection. Among several species of mammals captured in the tropical dry forest, Leishmania chagasi was isolated from 22.7% (5 of 22) D. marsupialis. This finding confirms the important role of opossums in Colombian foci of visceral leishmaniasis, including those where the phlebotomine species involved in transmission is Lutzomyia evansi, an alternative vector to the more common Lutzomyia longipalpis. PMID- 8203704 TI - Epidemic cholera in Trujillo, Peru 1992: utility of a clinical case definition and shift in Vibrio cholerae O1 serotype. AB - Epidemic cholera continues in Peru. Since 1991, cholera surveillance in Peru has been based mainly on clinical recognition. To determine the proportion of reported cholera patients who actually have cholera and to evaluate the clinical case definition used in surveillance, we cultured rectal swabs from patients presenting with acute diarrhea in March 1992 in Trujillo, Peru. Of 197 patients meeting the clinical case definition, 174 (88%) had confirmed Vibrio cholerae O1 infection. In this epidemic setting, watery diarrhea of sudden onset in a person of any age presenting for treatment is highly predictive of cholera. Of note, 90% of the current V. cholerae O1 El Tor isolates were of serotype Ogawa, while a year earlier, all were of serotype Inaba. PMID- 8203705 TI - First isolations of arboviruses from phlebotomine sand flies in West Africa. AB - For the first time in West Africa, arboviruses were isolated from phlebotomine sand fly pools. One strain of Chandipura virus (a Vesiculovirus), four strains of Saboya virus (a Flavivirus), and one strain of a not yet identified virus were isolated. Three hundred twenty-two pools were established from a population of 33,917 sand flies caught in CO2 light traps in the Ferlo Sahelian region of Senegal from November 1991 to December 1992. This is the first isolation of Chandipura virus from any arthropod in Africa. Saboya virus has already been isolated from small rodents in Senegal; thus, its transmission cycle probably involves rodentophilic sand flies. No strain of Rift Valley fever phlebovirus, which caused an epizootic in this region in 1987, was isolated. During the same time at the same site, 11 sand fly species were identified from 4,191 specimens caught on sticky traps, including Phlebotomus duboscqi, a leishmaniasis vector. PMID- 8203706 TI - Morbidity due to heavy Schistosoma mansoni infections in a recently established focus in northern Senegal. AB - A study of morbidity due to Schistosoma mansoni infection was carried out in Ndombo, a recently established but intense focus in northern Senegal. A random population sample (n = 422) was examined by repeated egg counts, standardized interviews, and clinical examinations. Egg counts were positive in 91%, with more than 1,000 eggs per gram of feces in 41% of the subjects. Abdominal discomfort was reported by 60% of the subjects, diarrhea by 33%; 17% of the stools were liquid upon inspection. Hepatomegaly was mostly mild and found in 7% of the subjects, mainly in males less than 20 years of age. Splenomegaly was detected in only 0.5% of the people examined. There was no significant correlation between the frequency of complaints or symptoms and egg counts. The remarkably mild morbidity in spite of the intense level of many infections may be explained by the recent nature of the focus; more severe chronic morbidity may develop in the future. PMID- 8203708 TI - Quantitative determination of circulating soluble egg antigen in urine and serum of Schistosoma mansoni-infected individuals using a combined two-site enzyme linked immunosorbent assay. AB - Two enzyme-linked immunosorbent assays (ELISA-5B1 using monoclonal antibody [MAb] 114-5B1-A [IgG1] and ELISA-4D12 using MAb 114-4D12-A [IgG3]) that detect circulating soluble egg antigen (CSEA) of Schistosoma mansoni were combined into one assay. This assay showed better performance than either of the two MAbs alone in detecting egg antigen, which was demonstrated with 80 urine samples from patients infected with Schistosoma mansoni from Zaire. The lower detection limit of the combined ELISA was 90 pg of the trichloroacetic acid-soluble fraction of soluble egg antigen (SEA-TCA) per milliliter. Thirty-two serum samples and 107 urine samples from uninfected Dutch individuals were negative when tested with the combined ELISA. This assay showed the same sensitivity (86.3%) with patients' urine samples as parallel testing with ELISA-5B1 and ELISA-4D12 (85%), while ELISA-5B1 and ELISA-4D12 showed sensitivities of 81.3% and 75%, respectively. The sensitivity of the combined ELISA with 51 serum samples was 84.3%, and three of five serum samples available from the seven patients with negative urine were positive for CSEA. The concentration of CSEA calculated from a four-parameters logistic curve for samples tested showed a correlation with egg output and serum circulating anodic antigen (P < 0.0001). Circulating soluble egg antigen in urine showed a significant decrease with an increase in age of the patients in relation to serum CSEA and egg output. PMID- 8203707 TI - Hematospermia: a new etiology of clinical interest. AB - Ten Spanish male tourists developed hematospermia and ultrasonographic evidence of involvement of the prostate and/or seminal vesicles after recreational exposure in bodies of fresh water in the Dogon country of Mali. Schistosoma eggs were detected in the ejaculate of five men, in the others, eggs were observed in the urine or feces. Three different species were observed: S. intercalatum, S. haematobium, and S. mansoni. Hemospermia and clinical prostatitis may be frequently unrecognized clinical manifestations of the early stages of infection in previously nonexposed persons. Travelers to endemic areas should be advised on the potential dangers of swimming and other exposure in bodies of freshwater. PMID- 8203709 TI - Myonecrosis due to Russell's viper bites in Sri Lanka. AB - Scattered or diffuse myonecrosis is the histopathologic basis for muscle pain and tenderness due to bites by Vipera russelli pulchella in Sri Lanka. These lesions may even occur without any clinical symptoms. Subclinical lesions may form one end of continuous spectrum, with the other being severe pain and muscle tenderness with rhabdomyolysis and myoglobinuria. Electromyographic abnormalities, when present, are suggestive of a myopathic pattern, rather than inflammatory muscle disease. A subclinical motor neuropathy may also occur. Hence, there is evidence for subclinical envenomation following bites by Russell's viper. Early antivenom therapy does not prevent the histologic, electromyographic, or nerve conduction abnormalities. PMID- 8203710 TI - Inappropriate secretion of antidiuretic hormone and hyponatremia in severe falciparum malaria. AB - Overhydration can contribute to fatal complications of falciparum malaria, even though renal function may be normal. In this context, the role of inappropriate secretion of antidiuretic hormone (ADH) has been controversial. Therefore, we have analyzed ADH serum concentrations together with serum osmolality and sodium levels in serum and urine of 17 consecutively studied patients with severe falciparum malaria. Serum sodium levels were low in 13 of 17 patients upon admission and returned to normal levels during antiparasitic therapy. Urine sodium levels were low in seven of 13 patients before treatment and increased during therapy. Urine sodium concentrations were high, however, in the remaining six patients. Serum osmolality was lower in these six patients than in the other seven hyponatremic patients (P < 0.002). In relation to serum osmolality, ADH levels were inappropriately high in these six patients, which confirms the presence of inappropriate secretion of ADH. Serum creatinine levels were not higher in these six patients than in those without inappropriate secretion of ADH. Inappropriate secretion of ADH seemed to be a major cause of hyponatremia, since other factors that could lead to this condition were not found in these six patients. In conclusion, we have shown, that human falciparum malaria can be associated with inappropriate secretion of ADH. PMID- 8203711 TI - Detection of the H1-j strain of Salmonella typhi among Korean isolates by the polymerase chain reaction. AB - Salmonella typhi, the etiologic agent of typhoid fever, typically has only a phase-1 flagellar antigen, H1-d (fliC). While most strains of S. typhi have H1-d antigen, 10-20% of Indonesian isolates have been reported to possess H1-j antigen instead. To investigate the presence H1-j strains of S. typhi isolates in Korea, where typhoid fever is still a common infectious problem, we used the polymerase chain reaction (PCR) with a pair of oligonucleotides primers that specifically amplified the flagellin gene of S. typhi. Of 375 isolates of S. typhi tested, only one was shown to possess the H1-j antigen, which was shown by the presence of a 1,269-basepair fragment on agarose gel electrophoresis after the PCR. The isolate with the H1-j antigen was cultured from a Korean-Indonesian man who was already symptomatic in Indonesia and was thought to be an Indonesian strain. Because 375 strains tested in this study were collected from cases with typhoid fever in different regions of Korea during the period from 1986 to 1991, it could be concluded that the mutation rate to j antigen is negligible among S. typhi endemic in Korea. PMID- 8203712 TI - Immunofluorescent visualization of the excretory and gut system of Schistosoma mansoni by confocal laser scanning microscopy. AB - Conventional epifluorescence microscopy (CEM) and confocal laser scanning microscopy (CLSM) were used to visualize the excretory system and the gut on whole organisms of different life-cycle stages of Schistosoma mansoni. To visualize the gut system, an anti-circulating anodic antigen (CAA) monoclonal antibody (MAb) (120-1B10-A) was used, whereas the excretory system was immunohistochemically stained with an anti-flame cell MAb (51-4H8-A) and with a recently described anti-egg MAb (114-5B1-A). The CEM procedure resulted in clear images at low magnification but the signal-to-noise ratio on the higher magnification images was very poor. Using CLSM on the adult worm, the 114-581-A MAb demonstrated a well-defined system of canals that could be morphologically identified as the excretory system. The flame cells terminating the branches of the excretory canals showed a clear immunoreactivity with the 114-5B1-A MAb as well as with the specific flame cell MAb. The gut system could be visualized, using an anti-CAA MAb, as two well-defined bands throughout the length of the parasite. Application of the 114-5B1-A MAb on cercariae revealed a strong fluorescence on the cercarial surface, whereas no immunoreactivity could be detected on internal structures. Whole eggs showed a bright fluorescence of the egg shell, whereas miracidia showed immunoreactivity of the germinal cells located in the center of the organism. The CLSM procedure, especially with the recently introduced fast photon-counting option, provides a superior tool to investigate the three-dimensional localization of different epitopes on immunofluorescently stained whole mounts of multicellular organisms in comparison with CEM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203713 TI - Evidence for guanosine triphosphate--binding proteins in Trypanosoma cruzi. AB - The transformation of the parasite Trypanosoma cruzi from the blood-borne trypomastigote to the intracellular amastigote constitutes a key clinical feature in the pathophysiology of Chagas' disease. That this transition occurs without change in the integrity of the plasma membrane of the parasite suggests the presence of biochemical structures, i.e., signal transduction systems, that convey information regarding the external milieu of the host so as to facilitate this transformation. In higher eukaryotes, it has been found that a heterotrimeric GTP-binding protein (G-protein), composed of alpha beta gamma subunits, constitutes a critical component of this complex. Two closely related groups of G-proteins are substrates for cholera toxin (CT)- (Gs) and pertussis toxin (PT)- (Gi1-3 and Go) dependent ADP ribosylation. In concert, they link plasma membrane receptors to adenylate cyclase, resulting in the stimulation or inhibition, respectively, of cAMP generation. In this report, we demonstrate the presence of both groups of G-proteins. Cholera toxin-dependent ADP ribosylation of 42- and 45-kD proteins was demonstrable in amastigotes (AMAST), in the cytosol of epimastigotes (EPI), and weakly in trypomastigotes (TRYP), suggesting the presence of the stimulatory GTP-binding protein, Gs, in T. cruzi. Antisera generated against the alpha s subunit of the Gs heterotrimeric protein (anti alpha s) bound to a 45-kD protein CT substrate in the rank order TRYP >> AMAST approximately EPI cytosol. Immunoprecipitation of CT-32P-ADP-ribosylated membranes with anti-alpha s resulted in 42- and 45-kD proteins. However, no Gs mediated activation of adenylate cyclase was demonstrable in reconstitution studies using cyc- lymphoma cells, which lack a functional Gs but possess a beta adrenergic receptor and adenylyl cyclase enzyme. Pertussis toxin-catalyzed ADP ribosylation was demonstrable in 39-40-kD particulate proteins of EPI, less strongly in AMAST, and least in TRYP, consistent with the presence of inhibitory (Gi) and Go GTP-binding proteins. In support of this observation, immunochemical analysis of the PT substrates identified the presence of alpha o and alpha i1-2-3 in EPI, AMAST and TRYP, although, with the exception of alpha i3, both toxin and associated immunochemical PT substrates are decreased in AMAST and TRYP relative to EPI. Although the functions of these putative G-proteins in T. cruzi are still unclear, their expression may be regulated by the state of parasite differentiation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8203714 TI - Use of recombinant DNA probes for species identification of Old World Leishmania isolates. AB - Recombinant DNA probes from a genomic Leishmania major library were screened for their potential to distinguish among Old World Leishmania taxa by Southern blot analysis. A probe, pDK10, was selected and tested on a panel of 58 Old World Leishmania strains that had already been typed isoenzymatically; these strains belong to the different species described so far and had been isolated from various hosts and vectors in 14 countries. In the present study, 45 zymodemes were represented. Using the pDK10 probe, we were able to differentiate between the different phenetic complexes. No variations in hybridization patterns were found within these complexes. In addition, there was a good concordance between identification based on DNA hybridization with the pDK10 probe and that based on isoenzyme typing. The probe has been applied in identifying Leishmania strains that were isolated in Tunisia from humans, animals, or insects. Our results show that the application of the pDK10 probe, in combination with a Pst I digestion of Leishmania DNA, could be a possible alternative to isoenzyme analysis for the identification of Leishmania strains. PMID- 8203715 TI - Proguanil plus sulfamethoxazole is not causally prophylactic in the Macaca mulatta--Plasmodium cynomolgi model. AB - New drugs for causal prophylaxis of malaria are needed. A proguanil/sulfamethoxazole combination was investigated using a rhesus monkey model (Macaca mulatta infected with Plasmodium cynomolgi) to determine whether causal prophylaxis could be achieved. When a five-day regimen of proguanil (40 mg/kg/day) combined with sulfamethoxazole (100 mg/kg/day) was used, infection of all animals (6 of 6) was observed, with an extended prepatent period (median 40 days). Two control animals became infected on days 9 and 23 following sporozoite inoculation. Plasma concentrations indicated that proguanil and sulfamethoxazole were adequately absorbed and metabolized to cycloguanil and N4 acetylsulfamethoxazole, respectively. Analysis of liver biopsy specimens demonstrated that the drugs were present two days following sporozoite inoculation but were not detectable one week later. Proguanil plus sulfamethoxazole does not eliminate exoerythrocytic-stage parasites in the rhesus monkey--P. cynomolgi model. PMID- 8203716 TI - Prevention of sporogony of Plasmodium falciparum and P. berghei in Anopheles stephensi mosquitoes by transmission-blocking antimalarials. AB - The sporontocidal activity of three 8-aminoquinolines, a 1,4-naphthoquinone, and three dihydroacridine-diones was determined against the ANKA clone of Plasmodium berghei and both chloroquine-sensitive (NF54) and chloroquine-resistant (7G8) P. falciparum. Anopheles stephensi mosquitoes previously fed on P. berghei--infected mice or P. falciparum--infected cultures were refed on uninfected mice treated previously with a given drug. Sporontocidal activity was determined by assessing both oocyst and sporozoite development. Neither primaquine nor menoctone exhibited sporontocidal activity against P. berghei or either strain of P. falciparum at a dose of 100 mg base drug/kg mouse body weight, whereas the other five compounds each effectively interrupted the sporogonic development of all three parasite strains at this dose. These data clearly demonstrate that experimental dihydroacridine-diones and 8-aminoquinolines are capable of interrupting the sporogonic development of P. berghei and chloroquine-sensitive and chloroquine-resistant P. falciparum. These data also suggest that the P. berghei model may be used to accurately predict sporontocidal activity against P. falciparum. PMID- 8203717 TI - Special symposium on mucosal immunity: protection against pathogens. Introduction. PMID- 8203718 TI - Mucosal immunization via M cells for production of protective secretory IgA antibodies. AB - Transepithelial transport of antigens by M cells in the epithelium associated with lymphoid follicles in the intestine delivers immunogens directly to organized mucosal lymphoid tissues, the inductive sites for mucosal immune responses. We have exploited M cell transport to generate and characterize specific monoclonal IgA antibodies that can prevent the interaction of pathogens with epithelial surfaces. The relative protective capacities of specific monoclonal IgA antibodies have been tested in vivo by generation of hybridoma tumors that result in the secretion of monoclonal IgA into the intestine. Using this method, we have established that the secretion of IgA antibodies recognizing a single surface epitope on enteric pathogens can provide protection against colonization or invasion of the intestinal mucosa. PMID- 8203719 TI - Lymphocyte compartments in antigen-sampling regions of rabbit mucosal lymphoid organs. AB - Uptake and delivery of antigens to immunocompetent cells in the gut are critical factors for the development of oral vaccines. Particulate antigens are transported within minutes by M cells to intraepithelial lymphocytes and into the follicle dome. The dome contains B cells, CD4+ T cells, and macrophages, indicating that the cells involved in antigen presentation are located below the dome's epithelium. The high number of M cells in rabbits and the development of monoclonal antibodies against rabbit lymphocytes have enabled the detailed study of lymphocytes associated with M cells. The follicle epithelium of rabbit Peyer's patches contains B cells and a population of CD4-/CD8-, major histocompatibility complex class II+ mononuclear cells of unknown function. These cells are phenotypically distinct from T cells in follicle domes, in T cell-dependent areas, in villus epithelium, or in villus lamina propria. In addition, lymphocytes in M-cell pockets express an activation antigen (3B6) not found on CD4+ or CD8+ cells in T cell-dependent areas. These results indicate that M-cell pocket lymphocytes in follicle epithelium form a phenotypically distinct compartment situated at the interface between M-cell-driven antigen uptake and the mucosal immune system. PMID- 8203720 TI - Human immunodeficiency virus infection and cryptosporidiosis: protective immune responses. AB - Cryptosporidium parvum is an ubiquitous protozoan parasite that infects the gastrointestinal track, leading to enteritis. The course of the disease is closely linked to the immunocompetence of the host. In patients with human immunodeficiency virus (HIV) infections, the CD4 cell count is the best marker of the ability of the immune system to clear Cryptosporidium infection at the mucosal surface. In HIV seropositive persons who have cleared Cryptosporidium infection, levels of specific anti-Cryptosporidium secretory IgA are elevated compared with persons with acquired immunodeficiency syndrome (AIDS) and chronic cryptosporidiosis. In contrast, anti-Cryptosporidium serum antibody responses are much greater in persons with AIDS and chronic Cryptosporidium infection. Secretory antibody is also effective in neutralizing Cryptosporidium infection in vitro. Secretory IgA may be responsible for recovery from infection or may only be a marker for an effective immune response at the mucosal surface. Specific defeats in secretory antibody responses in patients with AIDS and cryptosporidiosis may be overcome with the development of murine or human monoclonal antibodies for oral immunotherapy. PMID- 8203721 TI - Mucosal microenvironment and mucosal response. AB - Considerable investigative effort is currently being directed towards the use of oral immunization for the prevention of mucosal infections, including otitis media, in infancy and childhood. The development of immune response to mucosally introduced vaccines or environmental antigens is significantly influenced by the mucosal microflora, enzymatic activity, factors influencing epithelial permeability and the nature of vaccine antigens administered. Studies carried out during the past several years have suggested that antigen uptake, antigen processing, and immune response to environmental antigens in the respiratory and intestinal mucosa are greatly altered by coexisting mucosal infections. High levels of ovalbumin or ragweed antigens were often observed in the serum associated with increased IgE-specific antibody responses following concurrent infection with respiratory syncytial virus, or rotavirus, respectively. The influence of the mucosal enzymatic environment has been recently evaluated after oral immunization with replicating poliovaccine or parenteral immunization with inactivated poliovaccines. High levels of neutralizing and VP3-specific antibody response and antibody activity against antigenic determinants generated in the intestine were observed characteristically after oral immunization with replicating virus. Such responses were conspicuously absent after parenteral immunization. These observations suggest that diverse elements of the mucosal microenvironment play an important role in the outcome of infections and development of immune responses at mucosal surfaces. PMID- 8203723 TI - Strategies for the induction of immune responses at mucosal surfaces making use of cholera toxin B subunit as immunogen, carrier, and adjuvant. AB - The concept of a common mucosal immune system, through which specific antigen activated lymphocytes from the gut can disseminate immunity both along the intestinal tract and to various other mucosal and glandular tissues, has generated much current interest in the possibility of developing oral vaccines, not only for enteric infections but also for infections in the respiratory and urogenital tracts. However, to date it has proven difficult in practice to stimulate strong mucosal IgA immune responses by either parenteral or oral mucosal administration of most antigens, and experience with soluble protein antigens has, on the whole, been disappointing. A notable exception in this regard is cholera toxin (CT) and in humans more than in other species, its nontoxic B subunit pentamer moiety (CTB). Based on this, CTB has become an important component in recently developed oral vaccines against cholera as well as against diarrhea caused by enterotoxigenic Escherichia coli producing CT-like heat-labile enterotoxin(s). Since the strong immunogenicity of CT and CTB can, to a large extent, be explained by their ability to bind to receptors on the intestinal mucosal surface, there has recently been much interest in approaches using CTB as an oral delivery carrier system for other vaccine-relevant antigens, and much progress has been made in preparing immunogenic hybrid proteins by coupling various protein or peptide antigens chemically or genetically to CTB. Indeed, in several systems, oral administration of such hybrid antigens has been found to markedly potentiate both intestinal and extraintestinal IgA immune responses against the CTB-coupled antigens and also to elicit substantial circulating antibody responses. Besides the mucosal immunopotentiating effect of either CT or CTB owing to their similar capacity as oral antigen-delivery vehicles, CT, but in most systems tested not CTB, also has strong adjuvant properties for stimulating mucosal IgA immune responses to admixed (not coupled) unrelated antigens after oral immunization. This adjuvant activity appears to be closely linked to the ADP-ribosylating action of CT (and specifically of its A subunit) leading to enhanced cyclic AMP formation in the affected cell, and efforts to eliminate the enterotoxic activity without losing adjuvanticity have so far not met with success. PMID- 8203722 TI - Role of mucosal secretory immunity in the development of an amebiasis vaccine. AB - Invasive colonic infection by the enteric protozoan Entamoeba histolytica elicits a mucosal anti-amebic IgA antibody response. The E. histolytica galactose inhibitable adherence protein (GIAP) mediates parasite binding to colonic mucins and epithelial cells. Anti-GIAP secretory IgA antibodies are found during invasive amebiasis and can be elicited by immunization of rats with the native protein. Entamoeba histolytica contains potent IgA degradative activities due to its cysteine-specific proteases. Research is needed to further understand the role of secretory antibodies in natural or vaccine-induced immunity to E. histolytica. PMID- 8203724 TI - Universal method for the facile production of glycolipid/lipid matrices for the affinity purification of binding ligands. AB - Glycolipid recognition is a common motif in cellular physiology and bacterial pathogenesis. Such protein/lipid interactions are most conveniently demonstrated by the thin-layer chromatogram overlay. We have designed a simple affinity matrix for the purification of such glycolipid (or lipid) binding ligands based on the same principle, i.e., glycolipid (or lipid) adsorbed onto silica. The versatility of the procedure is demonstrated by the purification of several anti-glycolipid antibodies and anti-phosphatidyl ethanolamine (anti-PE) and the affinity purification of the Escherichia coli-derived verotoxin which binds to globotriaosyl ceramide. PMID- 8203725 TI - Stability of high-energy substrates in fast- and slow-twitch muscle: comparison of enzymatic assay of biopsy with in vivo 31P nuclear magnetic resonance spectroscopy. AB - The purpose of this study was to investigate the stability of ATP and PCr levels in stored muscle samples and extracts. ATP and PCr levels were measured by fluorimetric analysis in freeze-clamped biopsies of soleus, extensor digitorum longus, and gastrocnemius muscles of the rat after storage in a freezer at -70 degrees C as (i) intact wet muscle, (ii) freeze-dried muscle, and (iii) an extract of freeze-dried muscle. Assays were performed within 24 h of taking the biopsy and after variable periods of storage from 1 to 4 weeks. The data for the gastrocnemius muscles were compared with those obtained, in the same rat, by in vivo 31P NMR spectroscopy. In the biopsies, the ATP levels were stable irrespective of the duration or method of storage. The PCr levels fell by 13-16% compared with the values obtained from the assay done within 24 h of taking the biopsy, irrespective of the method of storage, but could be corrected in the freeze-dried stored muscle by expressing the data in relation to the total creatine levels. The fluorimetrically measured PCr, in whole muscle extracts of the gastrocnemius, assayed within 24 h, were comparable to those obtained from 31P NMR spectroscopy. We concluded that PCr levels in muscle are not stable during storage at -70 degrees C and should be assayed within 24 h of taking a muscle biopsy to ensure that the values are the same as those obtained by 31P NMR. PMID- 8203726 TI - A novel chemical procedure for the selective removal of nonreducing terminal N acetyl hexosamine residues from glycolipids. AB - A two-step oxidative hydrolysis procedure is described for the selective removal of nonreducing terminal N-acetylhexosamine residues from glycolipids. The procedure gives a 50-60% yield of the n-1 hexosyl ceramide, the remainder being peeling products (n-2, n-3, etc.). The reaction is dependent on the selective deacetylation of nonreducing terminal N-acetyl hexosamine residues by aqueous base hydrolysis. Deglycosylation then occurs in the presence of hydrogen peroxide. Glycolipids containing internal or no N-acetylhexosamine residues are unaltered in these reactions. This method is suitable for the large-scale deglycosylation of appropriate glycolipids and may also be used as an adjunct in structural determination of unknown amino sugar-containing glycolipids. PMID- 8203727 TI - Antibody-antigen binding constants determined in solution-phase with the threshold membrane-capture system: binding constants for anti-fluorescein, anti saxitoxin, and anti-ricin antibodies. AB - Affinities of various monoclonal and polyclonal antibodies for fluorescein containing antigens, saxitoxin and ricin, were determined by using a light addressable potentiometric sensor-based system (Threshold). The dissociation constants, determined from Scatchard plots, ranged from 2 x 10(-7) to approximately 3 x 10(-12) M. Dissociation constants for fluorescein and saxitoxin were compared with values determined by independent means. This technique was found to be quick, simple, reproducible, and accurate. PMID- 8203728 TI - Biotinylated and cysteine-modified peptides as useful reagents for studying the inhibition of cathepsin G. AB - An assay for studying the proteolytic activity of endopeptidases using a biotinylated and cysteine-modified peptide has been developed. This assay is rapid, sensitive, and reproducible. Although used here specifically for the enzyme which cleaves at the amino terminus (N-terminus) of beta-amyloid peptide (BAP); this type of radiolabeled substrate is readily applied to the analysis and detection of other endoprotease activities. This method relies on a peptide substrate which contains: (a) the amino acids flanking the enzymatic cleavage site, (b) an added cysteine at the carboxy-terminus to allow for incorporation of radiolabel via an addition reaction with tritiated N-[ethyl-1,2-3H]maleimide (3H NEM), and (c) a biotin at the N-terminus to allow for binding to avidin-coated scintillation proximity assay (SPA) beads. It has been suggested that the enzyme involved in the N-terminal cleavage of amyloid precursor peptide to generate BAP is a chymotrypsin-like serine protease such as cathepsin G. To study this enzymatic activity and to screen for its inhibitors, we have synthesized the peptide biotin-SEVKMDAEFdC which contains the amino acids flanking the N-terminal cleavage site of BAP. Tritiated NEM is covalently bound to the cysteine at the carboxy-terminal end and the labeled peptide is purified by reverse-phase high performance liquid chromatography. Following digestion of 3H-NEM-labeled peptide by cathepsin G, the biotinylated side of the cleaved peptide is bound to the SPA bead, while the tritiated end of the cleaved peptide remains in solution. Enzymatic hydrolysis is measured as the loss of 3H-induced scintillation signal. This method has allowed us to rapidly determine kinetic constants and develop a high throughput screen to study inhibition of cathepsin G cleavage in a native peptide context. PMID- 8203729 TI - A method for obtaining 13C isotopomer populations in 13C-enriched glucose. AB - 13C NMR analysis of 13C-enriched glucose containing multiple isotopomers is hampered by chemical shift similarities of several carbon resonances and by the presence of two anomeric forms. A convenient and quantitative method of enzymatically oxidizing glucose to gluconate in tissue and perfusate extracts is presented. The six carbon resonances of the resulting 13C-enriched gluconate are fully resolved at high pH, thereby allowing a determination of the fractional population of each 13C isotopomer by 13C NMR. The utility of this method is demonstrated using the effluent from an isolated perfused liver containing 13C enriched glucose produced by hepatic metabolism of sodium [1,2,3-13C3]propionate via the citric acid cycle and gluconeogenesis. An analysis of the gluconate C2 and C5 resonances in this sample showed that pentose phosphate activity was insignificant during this perfusion protocol. As demonstrated, this method provides a means of fully describing 13C isotopomer populations in enriched glucose samples where isotope may be derived from multiple metabolic pathways, thus expanding the scope of experimental design and enrichment strategies. PMID- 8203730 TI - Soaking nitrocellulose blots in acidic buffers improves the detection of bound antibodies without loss of biological activity. PMID- 8203731 TI - Frit-fast atom bombardment liquid chromatography/mass spectrometry, a useful method for sequencing dinucleotides. PMID- 8203732 TI - An assay for phosphatidylserine decarboxylase using BondElut columns. PMID- 8203733 TI - Relief of DNA polymerase stop(s) due to severity of secondary structure of single stranded DNA template during DNA sequencing. PMID- 8203734 TI - In situ hybridization with strand-specific DNA probes generated by a two-step polymerase chain reaction procedure. PMID- 8203735 TI - Proteolysis of a membrane-bound protein in polyacrylamide gel slices using freeze pulverization and gel electrophoresis techniques. PMID- 8203736 TI - 1-Hexadecyl-2-arachidonoylthio-2-deoxy-sn-glycero-3-phosphorylcholine as a substrate for the microtiterplate assay of human cytosolic phospholipase A2. AB - Human cytosolic phospholipase A2 (cPLA2) is an 85-kDa protein which displays a preference for arachidonoyl phospholipids as substrates. This substrate preference and the assay characteristics of the enzyme are quite different from those of the smaller, more well-studied extracellular PLA2s. We now report the development of a nonradioactive, spectrophotometric, microtiterplate assay for human cPLA2 using a novel synthetic thio-phospholipid analog as a substrate. This substrate is a phosphatidylcholine derivative with an arachidonoylthioester in the sn-2 position and an alkyl-ether in the sn-1 position. The use of an sn-1 alkyl-ether in the substrate ensures that the assay will only measure PLA2 activity and will not be complicated by the metabolism of the lysophospholipid product by the enzyme's lysophospholipase activity. cPLA2 is assayed at pH 7.4 and 37 degrees C with a mixed micellar substrate consisting of 2 mM thio phospholipid and 4 mM Triton X-100 in 30% glycerol. Under these conditions, the assay is fairly linear for over 1 h. PMID- 8203737 TI - Protein kinase C as a measure of transbilayer phosphatidylserine asymmetry. AB - The endogenous phosphatidylserine of normal erythrocytes is confined to the cytoplasmic leaflet of the membrane. However, under pathologic conditions transmembrane asymmetry can be altered and cytofacial phosphatidylserine may appear on the cell surface. A sensitive alternative method for the measurement of the exposed phosphatidylserine content of erythrocyte membrane was developed using the activation of exogenous protein kinase C. Erythrocytes containing exogenous phosphatidylcholine incorporated into the outer membrane monolayer do not stimulate protein kinase C activity more than untreated cells. In contrast, red cells that have exogenous phosphatidylserine incorporated into their membrane outer monolayer, by prior inhibition of the aminophospholipid transporter, stimulate protein kinase C significantly more than red cells in which exogenous phosphatidylserine is allowed to translocate to the inner membrane monolayer. Kinase activation is comparable for normal cells and cells not exposed to lipid in which the aminophospholipid transporter is inhibited with sulfhydryl reagents (diamide or N-ethylmaleimide). However, Ca(2+)-loading results in an increase in activation of protein kinase C over control cells, consistent with previous reports that Ca2+ induces the exposure of erythrocyte and platelet phosphatidylserine. By reference to protein kinase C activation by phosphatidylserine in model systems, the quantity of phosphatidylserine on the cell surface may be estimated. Thus, protein kinase C activation affords a sensitive and specific measure of phosphatidylserine in the outer monolayer of biological membranes. PMID- 8203738 TI - Micellar electrokinetic capillary chromatography for determination of indolyl glucosinolates and transformation products thereof. AB - Micellar electrokinetic capillary chromatography based on dodecyltrimethylammonium bromide as a surfactant has been developed for the qualitative and quantitative determination of indolylic compounds. Indolyl glucosinolates (indol-3-ylmethylglucosinolates), its degradation products, and further transformation products thereof have been included in the studies. The influence of various parameters on the separation has been investigated, resulting in efficient separation, even for structurally closely related compounds, with theoretical plate number per meter of capillary of up to 370,000 for some compounds. Repeatability and linearity of the method have been determined giving relative standard deviations for the migration times of the compounds between 0.5 and 0.9% and linear correlation coefficients between 0.9924 and 0.9996, respectively. The method can be successfully applied to follow the degradation of indolyl glucosinolates in detail. PMID- 8203739 TI - Chiral separation by capillary affinity zone electrophoresis using an albumin containing support electrolyte. AB - Chiral separations of some pharmaceutical compounds were studied by capillary affinity zone electrophoresis. Bovine serum albumin (BSA) was used as a chiral selector and added to electrolyte. For the chiral separation of new quinolone bactericidal reagents, phosphate buffer was more appropriate than borate buffer solution as the support electrolyte. The effects of BSA concentration, albumin type, pH, chiral additive, and voltage on separation were observed. As a result, chiral separations were performed in the pH range 7-8. The migration and stereoselectivities of enantiomers were changed by varying the protein concentration (more than 0.2% w/v) and voltage and by adding amino acids as chiral modifiers. This procedure is easily applicable to other compounds for chiral separation or for studies of protein binding interaction. PMID- 8203740 TI - Enzyme immunoassay to determine heavy metals using antibodies to specific metal EDTA complexes: optimization and validation of an immunoassay for soluble indium. AB - An immunoassay that measures soluble indium at concentrations from 0.005 ppb to 320 ppm is described. The assay utilized a monoclonal antibody that binds specifically to indium-EDTA complexes in an antigen-inhibition format. The sensitivity of the assay could be modulated by changing the nature of the soluble inhibiting antigen. The range of the assay was from 0.6 to 320 ppm, 0.1 to 120 ppm, or 0.005 to 2000 ppb when indium-EDTA, indium-(p-nitrobenzyl)-EDTA, or indium-EDTA-bovine serum albumin, respectively was used as the soluble inhibiting antigen. The assay reliably monitored indium concentration in the presence of a 100-fold excess of manganese, magnesium, or copper ions and the quantitation of indium by immunoassay correlated closely with the values obtained using atomic absorption spectroscopy. This technology could be employed in immunoassays for other metals that are priority pollutants. PMID- 8203741 TI - A kinetic approach to the selection of a sensitive spin trapping system for the detection of hydroxyl radical. AB - The spin trap 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) alone, as well as DMPO or N tert-butyl-alpha-phenylnitrone (PBN) in the presence of excess dimethyl sulfoxide (Me2SO), have been used as spin trapping systems for the detection of hydroxyl radical. However, the instability of DMPO and many of its corresponding spin trapped adducts has limited the usefulness of this spin trap, particularly in biological systems. Spin trapping of multiple free radicals by the PBN/Me2SO system may undermine the sensitivity of this method to detect small, yet biologically significant amounts of hydroxyl radical. The present study was undertaken to select a spin trapping system with greater sensitivity and selectivity toward.OH than DMPO, DMPO/Me2SO, or PBN/Me2SO. We report that alpha hydroxyethyl radical, resulting from the reaction of photolytically generated.OH with excess ethanol is spin trapped by 4-pyridyl-1-oxide-N-tert-butylnitrone (4 POBN) with a second-order rate constant nearly 10-fold greater than that for DMPO or PBN. In contrast to DMPO spin-trapped adducts, the alpha-hydroxyethyl radical adduct of 4-POBN, 4-POBN-CH(CH3)OH, is resistant to reduction by superoxide, even in the presence of cysteine. The efficiency of spin trapping and the marked stability of the resulting spin-trapped adduct confer a high degree of sensitivity and demonstrate the potential application of 4-POBN/ETOH toward the detection of hydroxyl radical in biological systems. PMID- 8203742 TI - Purification of antimicrobial peptides from an extract of the skin of Xenopus laevis using heparin-affinity HPLC: characterization by ion-spray mass spectrometry. AB - A simple scheme was developed for the rapid purification of antimicrobial peptides from the skin of Xenopus laevis. An extract of the frog skin was prepared using an acidic medium designed to maximize the solubilization of low molecular-weight peptides. This extract was subjected to an enrichment procedure using C18 Sep Pak cartridges to yield a salt-free fraction, devoid of high molecular-weight proteins. This fraction was in turn subjected to heparin affinity high-performance liquid chromatography on a Shodex AF-Pak column. All the antibacterial activity bound to the column and could be eluted using a linear gradient of increasing sodium chloride concentration. Antibacterial activity emerged from the column in fractions corresponding to a sodium chloride concentration of 0.45 M. Reversed-phase high-performance liquid chromatography resolved this material into a series of compounds which could be readily characterized using a combination of amino acid analysis and ion-spray mass spectrometry. Each peptide was found to be antimicrobial and each was positively identified as belonging to a family of amphipathic helix-forming peptides characterized by other investigators. Listed in their order of elution from the reversed-phase column the peptides were magainin 2, magainin 1, peptide-glycine leucine amide, xenopsin precursor fragment, levitide precursor fragment, and a mixture of fragments derived from the caerulein precursor. These peptides owe their antimicrobial properties to a predeliction to forming amphipathic alpha helical structures when associated with lipid membranes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203743 TI - Quantitative western blotting using [gamma-33P]ATP and the ultrasensitive bio imaging analyzer. AB - This report describes a method for simultaneous quantitative determination of antigens from protein blots based on the highly sensitive "contact-copy" procedure, applying the phosphorylation reaction as a general detection principle. Using ultrasensitive bio-imaging analyzer systems permits us to quickly and easily quantify single bands directly from the picture screen and to achieve a high-resolution printing of the image (pictography). By applying a new kanamycin loading procedure it is possible to use phosphocellulose paper P81 as a substrate matrix. Replacing 32P with 33P as a detection isotope leads to an improvement of the sensitivity, resolution, and safety. The method is applied to analyze the proteins dystrophin, myosin, vinculin, and desmin from human tissue lysates. The high sensitivity of the procedure (detection limit approximately 1 pg dystrophin) permits determination of the quantity of dystrophin in very small tissue biopsy samples, which is of special interest for Duchenne/Becker muscular dystrophy diagnosis. PMID- 8203744 TI - Method for efficient pelleting of small unilamellar model membrane vesicles. AB - Separation of model membrane vesicles from external solution is an important step in quantification of vesicle-associated materials. Ordinarily, such experiments cannot be done with small unilamellar vesicles because they are too small to be pelleted by centrifugation. A method is described that overcomes this difficulty by use of brominated phospholipids. It is shown that efficient pelleting of small unilamellar vesicles (greater than 98%) can be obtained by ultracentrifugation. PMID- 8203745 TI - Anti-galactosyl antibodies that react with unmodified agarose: a potential source of artifacts in immunoaffinity chromatography. AB - Rabbits were immunized with glycolipid and membrane glycoprotein extracts of the promastigotes of Leishmania major partially purified by two-phase extraction with Triton X-114. The resulting antibodies were affinity purified on agarose immunoadsorbents to which a recombinant DNA-produced L. major polypeptide had been coupled. In addition to the expected reaction with the polypeptide, it was found that the affinity-purified antibodies reacted strongly with lipophosphoglycan of L. major amastigotes and to a lesser extent with the lipophosphoglycan of promastigotes. Antibodies with this reactivity could be affinity purified on unmodified agarose and were probably directed against beta 1,3-galactosyl determinants shared between the agarose matrix and Leishmania. In this and other special situations the properties of the support matrix can be exploited to obtain antibodies of defined specificity which may be useful probes for the identification and characterization of carbohydrate structures. This work also points to a potential source of artifacts in affinity chromatography, in which the bead matrix is usually considered as inert. Carbohydrate antigens are ubiquitous, particularly in micro-organisms, and the presence of such antibodies may be more common than previously recognized. PMID- 8203746 TI - Gene transfer into mammalian cells by particle bombardment. AB - Using COS-7 and Chinese hamster ovary cells as model systems, I have examined the efficiency of gene transfer into mammalian cells by particle bombardment. The most important parameters affecting transformation efficiency are the size of the particles, the target distance, and the extent of chamber vacuum. The size of the cell culture plate also affects transformation efficiency. Factors which have little effect on transformation efficiency are the helium pressure, the gap distance, and the macrocarrier travel distance. Compared to several other gene transfer techniques, particle bombardment has the advantage of requiring a low amount of DNA and a low number of cells for successful expression, measured as either transient or stable. I also describe transformation of several murine cell lines which have not been successfully transformed, or have been transformed at only low levels using other methods. These cell lines include preadipocytes (BMS 2), macrophages (J774), and transformed pre-B cells (38B9 and 70Z/3). Compared to transformation by electroporation, lipofection, and diethylaminoethyl dextran, particle bombardment was found to give 50- to 240-fold higher levels of transient expression as measured by luciferase activity in cell extracts. PMID- 8203747 TI - Synthesis of squaraine-N-hydroxysuccinimide esters and their biological application as long-wavelength fluorescent labels. AB - We describe the synthesis and the fluorescence spectral characterization of two conjugatable long-wavelength fluorescence probes. These probes consist of a squaraine moiety, which is a cyanine-type chromophore with a central squarate bridge, and a reactive N-hydroxysuccinimide group for coupling with amino functions. One form is water soluble due to the presence of a sulfobutyl group; the other is water insoluble. The water-insoluble form was reacted with taurine to achieve water solubility and this squaraine-taurine conjugate displayed a very high affinity for bovine serum albumin. The squaraines exhibit short lifetimes and low quantum yields in water, with a significant increase in lifetime and quantum yield when bound to proteins. Their absorption maxima around 635 nm in water and 640 nm when bound to proteins allow excitation with the newly commercially available diode laser sources at 635, 645, and 650 nm. The spectral properties and photostabilities of the water-soluble squaraine probes are compared with those of the commercially available CY5-NHS ester. PMID- 8203748 TI - Application of bacterial artificial chromosomes to the generation of contiguous physical maps: a pilot study of human ryanodine receptor gene (RYR1) region. AB - In order to increase the rate of generation of a contiguous human chromosome 19 physical map, we have investigated the advantages of using a bacterial artificial chromosome (BAC) library in comparison with other systems. This cloning system, recently described, can faithfully propagate DNA fragments greater than 300 kb in size. We have screened a total human genomic BAC library with a complex cosmid probe, specific for the ryanodine receptor gene (RYR1) located at 19q13.1. One 150-kb BAC was positive for the ryanodine receptor probe. The ryanodine receptor BAC hybridized to a 150-kb overlapping set of nine chromosome 19-specific cosmids at the 3' terminus of the RYR1 gene as well as two established cosmid contigs which can be linked to the same physical region. The hybridization of the BAC to a 150-kb set of chromosome 19 cosmids suggests that this BAC is nonchimeric in structure. PMID- 8203749 TI - Characterization of rabbit myocardial phospholipase A2 activity using endogenous phospholipid substrates. AB - We have developed an assay for studying myocardial phospholipase A2 activity by measuring accumulation of lysophospholipids resulting from hydrolysis of the endogenous choline glycerophospholipid pool. This assay was used to characterize phospholipase A2 activity in rabbit myocardium. Lyophilized rabbit myocardium was incubated at 37 degrees C in Tris-HCl buffer containing either ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA)/EDTA or calcium, and palmitoyl-lysophosphatidylcholine (P-LPC), oleoyl-LPC, stearoyl-LPC, and 16:0 lysoplasmenylcholine were measured using a recently developed HPLC method. The identity of the individual species was confirmed by ion-spray LC-MS-MS. In the presence of EGTA/EDTA, incubation for up to 30 min caused a linear increase in all lysophospholipids. The main increases were found in P-LPC and 16:0 lysoplasmenylcholine, which increased by 37 +/- 3 (mean +/- SE, N = 8) and 48 +/- 3 nmol/g dry wt x min, respectively. The apparent phospholipase A2 activity was found to be calcium, temperature, and pH sensitive. The pH optimum was between 6.5 and 8.0, and incubation at room temperature and 45 degrees C decreased the activity by 80 and 40%, respectively. Studies of the metabolism of the formed lysophospholipids showed a substantial metabolism of the lysophospholipids that accounted for about 40% of the total phospholipase A2 activity. This method offers a novel approach to study phospholipase A2 activities by measuring accumulation of products resulting from hydrolysis of endogenous phospholipid pools. PMID- 8203750 TI - Analysis of molecular masses and oligomeric states of protein complexes by blue native electrophoresis and isolation of membrane protein complexes by two dimensional native electrophoresis. AB - Blue native Electrophoresis is a "charge shift" method developed for isolation of native membrane protein complexes from biological membranes that also separates both acidic and basic water-soluble proteins at a fixed pH of 7.5. In combination with a second dimension sodium dodecylsulfate electrophoresis it provides an analytical method for the determination of molecular mass and oligomeric state of nondissociated complexes, of subunit composition, and of degree of purity and for the detection of subcomplexes. The method was applied to analysis of cytochrome bc/bf complexes. By combination of a novel colorless native polyacrylamide gel electrophoresis (CN-PAGE) with blue native BN-PAGE, a two-dimensional native technique was developed that is suitable for preparation of highly pure membrane protein complexes. PMID- 8203751 TI - Isolation and identification of cecropin antibacterial peptides from the extracellular matrix of the insect integument. AB - A method for the screening and isolation of antibacterial peptides from the extracellular insect cuticle using ultrafiltration and reverse-phase high performance liquid chromatography is presented. Using this method we were able to conveniently isolate cuticular antibacterial peptides belonging to the cecropin family in 1 day. The procedure should facilitate the rapid screening of antibacterial peptides or other bioactive peptides from extracellular matrices. PMID- 8203752 TI - Determination of a monoclonal antibody binding activity using immunodetection. AB - A method for measuring the binding of chimeric IgG BR-96 to the Lewis Y antigen using the ImmunoDetection technology has been developed. The procedure is rapid (2 min), highly reproducible (< 5% CV), and has excellent correlation with the Lewis Y and anti-idiotypic enzyme immunoassays. Samples that were degraded by heat or by repeated freeze-thaw cycles showed reduced binding activity. There was minimal cross-reactivity with other proteins typically found in hybridoma media or with another chimeric IgG directed against a different antigen (L6). The fact that this assay can be performed using conventional HPLC equipment makes it especially attractive because it can be completely automated using equipment readily available. PMID- 8203753 TI - Detection of HIV1 DNA in biological samples by an homogeneous assay: fluorescence measurement of double-stranded RNA synthesized from amplified DNA. AB - A nonisotopic homogeneous detection of nucleic acid sequences after amplification is described. We show that a DNA fragment bearing T7 RNA polymerase promoters on each extremity is able to be transcribed in two complementary RNAs, leading to a high yield direct synthesis of double-stranded RNA (dsRNA). Thus, this dsRNA can be easily detected and quantified in solution by fluorescence in the presence of propidium iodide. This reaction, used as a postamplification step, has been associated with a nested polymerase chain reaction (PCR); the second PCR round allowing the incorporation of the T7 promoters. This leads to a very efficient homogeneous assay. The fluorescence signal is proportional to the concentration of PCR product and is highly specific. This method can be easily carried out with currently available reagents and with unsophisticated instrumentation. This homogeneous procedure has been evaluated for the detection of HIV1 in blood samples; the sensitivity and the specificity appear to be equivalent to that of the radioactive method. PMID- 8203754 TI - Synthesis of a N'-alkylamine anticoagulant active low-molecular-mass heparin for radioactive and fluorescent labeling. AB - Heparin plays an important role in anticoagulation and several other biological processes. Cleavage of heparin by nitrous acid results in a reactive 2,5 anhydromannose (Am) which can be used to selectively insert primary and secondary amines by reductive amination. Low-molecular-mass heparin (LMMH) was bound to 4 (2-aminoethylphenol) as shown by nuclear magnetic resonance spectroscopy (NMR), high-performance size-exclusion chromatography (HPSEC), polyacrylamide gel electrophoresis (PAGE), and ultraviolet/visible (uv/vis) spectroscopy. 1H NMR spectra revealed an average sequence of (IdoA2SO3-GlcNSO36SO3)9-IdoA2SO3-Am tyramine and a 50% binding rate of tyramine to LMMH. LMMH-Tyr had an anticoagulant activity of 108 antifactor Xa activity (aXa) U/mg and 42 antifactor IIa activity (aIIa) U/mg. The compound was neutralized by protamine. The N alkylamine derivative was adopted to label LMMH with iodine-125 by oxidation with chloramine T. Fluorescein-5-isothiocyanate (Fitc) was used to label LMMH-Tyr with fluorescence. NMR, HPSEC, PAGE, and uv/vis spectroscopy demonstrated the binding of Fitc to LMMH-Tyr. 1H NMR spectra indicated that about 80% of the LMMH-Tyr was labeled at the secondary amino group. The fluorescent compound exhibited 70 aXa and 5 aIIa U/mg and was neutralized by protamine. The selectively bound labeled heparin derivatives are "endpoint attached" and have intact anticoagulant activity. PMID- 8203755 TI - Quantitation of the diacyl, alkylacyl, and alk-1-enylacyl subclasses of choline glycerophospholipids by chemical dephosphorylation and benzoylation. AB - A method for the determination of the relative amounts of the diacyl, alkylacyl, and alk-1-enylacyl subclasses of choline glycerophospholipids by benzoolysis is described. The procedure consists of simply heating the phospholipid with benzoic anhydride in the presence of boric acid for 5 h at 100 degrees C, followed by reaction with 4-dimethylaminopyridine for 2 h at room temperature and HPLC analysis of the lipidic products formed. With model compounds of the three subclasses it is shown that diacyl- and alkylacylglycerophosphocholines are completely dephosphorylated by this procedure, yielding quantitatively the corresponding diacyl- and alkylacylglycerobenzoates. The same procedure applied to a model alk-1-enylacylglycerophosphocholine gives only 53.5% of dephosphorylation, while the dephosphorylated products in turn are quantitatively converted into the corresponding acylglycerodibenzoates. The latter figure is shown to be fairly reproducible. The reduced dephosphorylation rate of plasmalogens appears to be due to complete disruption of the vinyl ether bond. The liberated fatty aldehyde gives rise to an addition product with benzoic anhydride, which was identified by gas chromatography-mass spectrometry. It is demonstrated that acyl migration occurring during the benzoolysis does not interfere with the HPLC separation of the glycerobenzoates and dibenzoates derived from the three distinct subclasses. Results of subclass determinations by benzoolysis of several natural diradylglycerophosphocholines are in good accordance with literature values. The agreement between the plasmalogen contents, determined by benzoolysis and by phosphorus determination following exposure to HCl and separation by thin-layer chromatography, is satisfactory. The reliability of the benzoolysis method is generally discussed. PMID- 8203756 TI - A selective precipitation purification procedure for multiple phosphoseryl containing peptides and methods for their identification. AB - Multiple phosphoseryl-containing sequences of proteins stabilize amorphous calcium phosphate and have been implicated in the regulation of biomineralization, protein structure, and enzyme activity. To facilitate studies on the identification and characterization of multiple phosphoseryl-containing sequences of proteins we have developed a simple and efficient purification procedure involving precipitation of Ca2+/ethanol-induced aggregates of the multiple phosphoseryl-containing peptides from enzymic digests. The multiple phosphoseryl-containing peptides of a tryptic digest of casein were selectively precipitated using Ca2+ (20 mol/mol protein) and 50% (v/v) ethanol at pH 3.5, 4.6, and 8.0. The individual peptides of the precipitates were purified using anion-exchange fast-performance liquid chromatography and reversed-phase HPLC and then identified by solid-phase sequence analysis and amino acid composition analysis after vapor-phase hydrolysis. Prior to sequence analysis the phosphopeptides were covalently coupled to arylamine membranes and the phosphoseryl residues converted to S-ethylcysteinyl residues by calcium-ion catalyzed beta-elimination in the presence of ethanethiol. The modified peptides were sequenced using an Applied Biosystems Inc. automated protein sequencer fitted with a membrane cartridge. Only peptides containing the cluster sequence Ser(P)-Ser(P)-Ser(P)- were precipitated by Ca2+/ethanol at pH 3.5. The pH 4.6 precipitate contained all the cluster peptides plus two diphosphorylated peptides containing -Ser(P)-Glu-Ser(P)- and -Ser(P)-Thr-Ser(P)-. At pH 8.0, a monophosphorylated peptide containing -Ser(P)-Glu-Glu- was also present in the precipitate with the diphosphorylated and cluster peptides. The recoveries of the peptides in the pH 8.0 selective precipitate ranged from 83 to 95% of that present in the hydrolysate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203757 TI - A procedure for the determination of 5-fluorouracil in tissue using microbore HPLC and fluorescence detection. AB - For the determination of the cytotoxic drug 5-fluorouracil in tissue, a sensitive and selective assay has been developed based on microbore high-performance liquid chromatography and fluorescence detection after pre-column derivatization with 4 bromomethyl-7-methoxycoumarin. 5-Chlorouracil was found to be an appropriate internal standard. A column switching protocol has been devised to separate the analyte from late eluting matrix components and the natural uracil. The drug can be determined at concentrations in the low ng/g wet tissue range with a detection limit of 3 ng/g; furthermore, the same protocol can be applied to analyze serum and plasma samples. The procedure was employed to determine the drug in samples taken from human liver tumors and metastases after an intra-arterial bolus administration and from epithelial carcinomas after systemic continuous application. PMID- 8203758 TI - Quantitation of urinary 7-methyladenine by gas chromatography-mass spectrometry using isotopically labeled internal standards. AB - We have developed a procedure for isolating and quantifying 7-methyladenine from rat urine following the administration to the rat of methylating agents, such as dimethylnitrosamine. Urinary 7-methyladenine and its trideutero isomer, added as an internal standard, were precipitated with silver nitrate, the precipitate was extracted with HCl, and the extract was further purified by C18-Sep-Pak chromatography. The recovered 7-methyladenine was then derivatized with pentafluorobenzyl bromide at alkaline pH for analysis by gas chromatography-mass spectrometry, indicating a bis(pentafluorobenzyl) conjugate, m/z 509. The mass spectrum of this derivative shows a major fragmentation ion at m/z 328 (and 331 for the trideutero derivative) resulting from the loss of one pentafluorobenzyl group. Levels of urinary 7-methyladenine above 150 pg could be detected from the ratio of the gas chromatography peak areas for these ions, using selective-ion monitoring. The method was selective for the 7-methyl isomer. The procedures developed for the syntheses of deuterated and tritiated 7-methyladenine, which were required for these studies, are also described. PMID- 8203759 TI - Covalent protein crosslinks: general detection, quantitation, and characterization via modification with diphenylborinic acid. AB - Progressive crosslinking of proteins appears to be a general phenomenon in aging cells and tissues. Crosslinked proteins can form insoluble aggregates which become increasingly resistant to proteolysis as more crosslinks form. However, most evidence for progressive crosslinking with age is indirect, and little is known about the chemical mechanisms involved. We have therefore developed a method for detection and isolation of any type of stable covalent crosslink from protein hydrolysates which requires no prior knowledge of the molecular structure of whatever crosslink(s) may be present. It utilizes the specificity of the diphenylborinic acid reagent for alpha-amino acid groups and the chromatographic properties and uv absorbance of the crosslink derivatives. The method is demonstrated using eight different crosslinks from collagen and fibrin, and a general procedure is given for detection of any type of crosslink in a protein hydrolysate. PMID- 8203760 TI - Biopolymer synthesis on polypropylene supports. I. Oligonucleotides. AB - We have modified polypropylene to serve as a new solid-phase support for oligonucleotide synthesis. The plastic is first surface aminated by exposure to an ammonia plasma generated by radiofrequency plasma discharge. The aminated polypropylene has been found to be useful as a support for the in situ synthesis of oligonucleotides from monomers. Furthermore, oligonucleotides synthesized on the surface of the plastic remain attached following deprotection and can be used directly for hybridization. PMID- 8203761 TI - A dot-blot assay of metabolically radiolabeled hyaluronan. AB - Glycosaminoglycans labeled in tissue culture in the presence of [3H]glucosamine were proteolytically solubilized and then precipitated with cetylpyridinium chloride onto a sheet of nitrocellulose using a dot-blot apparatus. The proportion of hyaluronan (HA) was calculated from parallel aliquots digested with Streptomyces hyaluronidase, an enzyme specifically degrading HA. A linear response of radioactivity was obtained for samples in the range of 50-10,000 cpm (1-1000 ng total HA) when the dots cut from the membrane were counted with liquid scintillation. Negligible interference from an excess of unincorporated precursor, chondroitin sulfate, and proteolytic tissue digest was observed. The assay was particularly convenient in measuring large numbers of samples with relatively low activity, such as testing the effects of different drug concentrations and analyzing chromatographic fractions. PMID- 8203762 TI - Microscale analysis of glycosphingolipids by methanolysis, peracetylation, and gas chromatography. AB - A method for the analysis of pure samples of individual glycosphingolipids by microscale methanolysis, peracetylation, and gas chromatography is described. Solvolysis of glycosphingolipids in dry methanolic HCl and peracetylation were conducted in a single 4.5-cm sealed capillary tube (2 mm i.d.), after which the products were directly injected into a gas chromatograph. Total-component analysis (i.e., analysis of the sugar, fatty acid, and sphingosine moieties) was possible after a 45-min chromatographic run. Time-course studies of the acid catalyzed methanolysis of Gal beta 1-4GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta 1 4Glc beta 1-1Cer ganglioside at 80, 110, and 150 degrees C showed that methanolysis was complete after 2 h at 110 degrees C. Rates of methanolysis of individual components were compared and the release of the fatty acid moiety from the long-chain base was shown to be the slowest reaction. The methanolysis of all glycosidic bonds were complete in 0.5 h. Peracetylated methanolysis products were very stable over time and provided for good gas chromatographic detection of subnanomolar amounts of hexose, hexosamine, fatty acid, sialic acid, and long chain sphingoid base components. Recoveries of fucose and N-acetylglucosamine were determined with reference samples of Fuc alpha 1-2Lac and lacto-N fucosylpentaose II. Applications of the method are presented for the component analysis of a gift mixture of NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-1Cer ganglioside and NeuAc alpha 2 6Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4Glc-Cer ganglioside and analysis of NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1Cer isolated from human plasma. PMID- 8203763 TI - A high-performance liquid chromatography method for measurement of oxidized glutathione in biological samples. AB - A high-performance liquid chromatography method to determine oxidized glutathione (GSSG) in biological samples with ultraviolet-visible detection using N ethylmaleimide to prevent reduced glutathione (GSH) oxidation is described. Previous methods based on high-performance liquid chromatography to quantitative GSH and GSSG are unsuitable for determining GSSG in biological samples. This is due to GSH oxidation during sample processing. N-Ethylmaleimide, but not iodacetic acid, prevents this oxidation. Blood GSH oxidation measured by the widely used method of Reed et al. (Anal. Biochem. 106, 55-62, 1980) can be as high as 24 +/- 6% (n = 6). When blood samples were assayed by our procedure, GSH oxidation was only 0.13 +/- 0.28% (n = 5). GSH can be determined enzymatically, i.e., with glutathione-S-transferase, but perchloric acid should not be used to deproteinize samples. Trichloroacetic acid (15% final concentration) may be used. This method allows an accurate calculation of the GSH/GSSG ratio, which is important for determining oxidative stress in tissues in various pathophysiological situations. PMID- 8203764 TI - A colorimetric microtiter plate assay for lysostaphin using a hexaglycine substrate. PMID- 8203765 TI - Membrane targeting of firefly luciferase: a new bioluminescent reporter gene. PMID- 8203766 TI - Study of the antiischemic action of EGb 761 in the treatment of peripheral arterial occlusive disease by TcPo2 determination. AB - In a randomized, placebo-controlled, double-blind, parallel study of 20 patients, the antiischemic effect of EGb 761 (Ginkgo biloba Extract) was studied by measuring the transcutaneous partial pressure of oxygen (TcPo2) during exercise. Transcutaneous oximetry during exercise provides a good, noninvasive estimation of local arterial perfusion and constitutes a real index of local and regional capillary perfusion. Twenty patients between the ages of forty-four and seventy three years suffering from claudicating atherosclerotic arterial occlusive disease in stage II according to the Leriche and Fontaine classification, diagnosed for more than a year and stable for three months, were included. The eligible patients received placebo for fifteen days under single-blind conditions. At the end of this preinclusion period, the eligibility criteria were checked and the patients were randomized to two treatment groups. The first group received 320 mg per day of EGb 761 for four weeks and the second group received placebo. The treadmill walking test was performed under standardized conditions at the same time of day and by the same investigator. In a comparison of the differences before and after treatment, the areas of ischemia decreased by 38% in the EGb 761 group but remained essentially stable (+5%) in the placebo group. This difference between groups is significant (F [1.18] = 4.91; P = 0.04) and the 95% confidence interval for the difference ranges from 0.89 to 3.87. This study confirmed significantly the rapid antiischemic action of EGb 761 and its value in the management of peripheral arterial occlusive disease at the stage of intermittent claudication. PMID- 8203767 TI - Flavonoids. A review of the pharmacology and therapeutic efficacy of Daflon 500 mg in patients with chronic venous insufficiency and related disorders. AB - Daflon 500 mg consists of 450 mg diosmin and 50 mg flavonoid expressed as hesperidin. The authors describe its effects on the microcirculation in chronic venous insufficiency: improvement of venous tone, inhibition of prostaglandin synthesis, protection against free radicals, activation of the complement system, and increased lymphatic drainage. The authors summarize studies of its therapeutic efficacy in reducing venous capacitance, distensibility, and emptying time; reducing capillary permeability; and increasing capillary resistance. PMID- 8203768 TI - Effects of pentoxifylline on choroidal blood flow in nonproliferative diabetic retinopathy. AB - OBJECTIVE: Diminished blood flow plays an important role in the progression of diabetic retinopathy. Since increased blood viscosity is a contributing factor to hypoperfusion, it was of interest to determine whether therapy intended to decrease blood viscosity and induce vasodilation could increase blood flow in patients with diabetic retinopathy. METHODOLOGY: Ten patients, 4 with nonproliferative diabetic retinopathy and 6 age-matched, nondiabetic controls, were studied by a noninvasive system to index choroidal blood flow. Pentoxifylline was administered daily at an oral dose of 400 mg tid in the diabetic patients for nine months. RESULTS: The control group had pulse amplitude = 2.87 +/- 0.67 mm Hg with pulsatile choroidal blood flow = 714 +/- 196 microL/minute. Reproducibility studies in the control group (6 patients measured on three separate occasions) demonstrated an intraclass correlation coefficient of reliability, r = 0.83. In the diabetic patients, pulsatile flow = 276 +/- 68 microL/minute, 61% lower than the age-matched nondiabetic subjects (P = 0.003). After nine months of pentoxifylline therapy the diabetic patients had an increase in pulsatile choroidal blood flow to 469 +/- 152 microL/minute (P < 0.002). CONCLUSIONS: Pentoxifylline therapy brought blood flow levels in the diabetic patients closer to those of the nondiabetic age-matched control population so that following therapy there was no statistically significant difference between the two groups although the former were still lower. The potential efficacy of pentoxifylline in improving ocular blood flow in patients with diabetic retinopathy should be tested in a large controlled clinical trial. PMID- 8203769 TI - Circulatory and plasma catecholamine responses to mental stress in young subjects with two different types of hypertension. AB - To determine whether any differences exist between young male subjects with elevated diastolic and systolic blood pressure (BP) and those with only an elevated systolic BP, the responses of BP and plasma catecholamines to a mental arithmetic test were studied in 11 young men (mean age of nineteen years) with BP of > or = 140/90 mm Hg at a routine health check-up (group I-hypertension [HT]), 26 age-matched men with only elevated systolic BP (> or = 140 mm Hg) (group II HT), and 12 age-matched normotensive (NT) men (< 140/90 mm Hg). During an arithmetic test, group I-HT showed a significantly higher increment of systolic BP (+14.5-18.0%) than group II-HT (+9.3-10.2%) and NT controls (+6.4-8.2%). However, no significant difference in BP response was seen between group II-HT and NT controls. Plasma norepinephrine in group I-HT showed a significant increase after the test, (171 +/- 23-->202 +/- 27 pg/mL), whereas group II-HT and NT controls showed no change. No significant difference occurred in epinephrine response among the three groups. These results suggest that the young male subjects with screening BP above 140/90 mm Hg are hyperreactive to a mental stress as compared with subjects with only elevated systolic BP or NT controls. PMID- 8203770 TI - Changes in blood pressure reactivity and 24-hour blood pressure profile occurring at puberty. AB - To evaluate blood pressure reactivity in children and its changes in adolescents, the acute pressor response to a video-game stress test and the noninvasive ambulatory blood pressure monitoring were evaluated in 62 healthy children divided into three age groups. Basal blood pressure values were measured according to the NIH Task Force. With baseline measures and body mass index controlled for, analysis of covariance showed that the video game provoked significant and incremental cardiovascular reactivity across the games in adolescents when compared with the two other groups of children. The same group of children showed also a significantly higher systolic ambulatory pressure during the daytime, whereas no significant difference was observed by basal BP measurement. In conclusion an increased reactivity to external stimuli was observed in adolescents, and this pattern was strictly associated with a higher daily blood pressure. PMID- 8203771 TI - Thrombocythemic erythromelalgia, primary erythermalgia, and secondary erythermalgia: three distinct clinicopathologic entities. AB - On the basis of clinical, laboratory, and histopathologic studies, the authors discern three distinct types of red, congested, and burning extremities that need to be distinguished for effective treatment according to their etiology: erythromelalgia in thrombocythemia, primary erythermalgia, and secondary erythermalgia. Each entry is discussed in turn. PMID- 8203772 TI - Effect of prostaglandin E1 analogue administration on peripheral skin temperature at high altitude. AB - The effect of prostaglandin E1 analogue on peripheral skin temperature was examined at high altitude, where local cold injuries are common owing to severe environmental conditions. The peripheral skin temperature at rest was significantly lower at higher altitudes. Oral administration of the prostaglandin E1 analogue limaprost reversed this temperature decrease, probably by enhancement of peripheral circulation. The temperature recovery rate after a cold water challenge was also improved after the administration of limaprost. This oral type of prostaglandin E1 analogue is strongly recommended as an effective prophylactic and therapeutic vasodilator for local cold injuries at high altitudes. PMID- 8203773 TI - The applicability of color-labeled microspheres in a rabbit model of ischemia reperfusion. AB - This study was designed to examine the ability of color-labeled microspheres to depict different states of myocardial perfusion in a rabbit model of ischemia reperfusion. A thread was passed under the left anterior descending artery (LAD) and the first left marginal artery of anesthetized New Zealand White rabbits. Blue-labeled microspheres (500/g body wt) were injected into the left atrium. The thread was tightened in rabbits belonging to the experimental group (n = 8), and red-labeled microspheres (500/g body wt) were injected. The snare was loosened, and yellow-labeled microspheres (500/g body wt) were injected before (n = 5) or after (n = 3) methylene blue injection. In animals belonging to the "sham" group (n = 4 and n = 2, respectively), the sequence of injections was similar, but the snare was not tightened. The animals were euthanized, and 0.3-1 g sections were cut from ischemic and nonischemic regions, as determined by methylene blue in the experimental subgroups and from the corresponding regions in the "sham" subgroups. The tissue samples were digested with 4 M KOH, ethanol 70%, and ultrasonication, and the microspheres were recovered by vacuum filtration. The dye was chemically removed from the microspheres, and the photometric absorption of each sample was determined. There was no significant difference between the experimental and "sham" groups in baseline uptake of blue-labeled microspheres. Rabbits belonging to the experimental subgroups had significantly lower mean uptake of red microspheres during ischemia relative to "sham" (0.51 +/- 0.08 vs 1.06 +/- 0.24 and 0.36 +/- 0.19 vs 0.91 +/- 0.12, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203774 TI - Transcutaneous oxygen tension measurement in patients with chronic arterial obstructive disease: reliability and long-term variability of the method. AB - Although transcutaneous oxygen tension (TcpO2) measurement may be useful for assessing changes in regional perfusion induced over time by drug or surgical treatment in patients with chronic arterial obstructive disease (CAOD), the reliability of the method over a long-term period is not know. To approach this problem, the authors evaluated retrospectively the behavior of TcpO2 measurement over time in patients with CAOD. To eliminate confounding influences due to the concomitant vascular disease at the limb level, data analysis was performed on TcpO2 measured at the right infraclavicular position. The median length of follow up ranged from twenty days in 34 patients to 832 days in 3 patients (n = 2 and n = 10 individual sequential replications respectively). Initial and final TcpO2 values did not differ significantly even at the longest follow-up term, which indicates that the parameter is constant over time. The intrapatient variation coefficient of TcpO2 (calculated over at least three individual replications) ranged between an average of 11% to 16.2%. The corresponding interpatient variation fluctuated between 15.5% and 33.4%, a variability explained to some extent by sex-related influences, but, at least in the range of this sample, not by age, arterial oxygen levels, or disease status. Thus TcpO2 levels per se are stable, implying that TcpO2 measurement has the potential to record consistent changes caused by specific therapeutic interventions or the clinical evolution of patients with CAOD. However, the intrapatient and interpatient variability of the method has to be taken into account when TcpO2 is used for the follow-up and the physiopathologic study of patients with CAOD. PMID- 8203775 TI - Thrombus detection on central venous catheters in the neonatal intensive care unit. AB - Between September, 1989, and September, 1992, 193 infants were investigated prospectively for development of central-venous-catheter-induced thrombosis. In 25 infants intracardiac or central-venous-catheter-induced thrombosis was demonstrated (13%). A slightly higher incidence of thrombosis was found in infants with umbilical catheters in comparison with infants with subclavian catheters, although no significant difference was demonstrated. The results make clear that central venous catheters in neonatal intensive care have considerable risk in developing central venous or intracardiac thrombosis, and echocardiography is an excellent technique for diagnosing these thromboses. PMID- 8203776 TI - Recurrent embolization during intravenous administration of tissue plasminogen activator in acute cardioembolic stroke. A case report. AB - Treatment with recombinant tissue plasminogen activator (rt-PA) has been applied in acute cardioembolic stroke to reopen the occluded vessel and improve the patient's neurologic deficit. However, the effect of this therapy on intracardiac thrombus has not been documented previously. A forty-five-year-old man with dilated cardiomyopathy developed acute cardioembolic stroke with disturbance of consciousness, right hemianopia, right hemiplegia, and global aphasia. Cerebral angiography demonstrated occlusion of the left middle cerebral artery trunk. Intravenous administration of 30 megaunits (MU) of recombinant tissue plasminogen activator was commenced two hours after the ictus and completed within sixty minutes. Cerebral angiography was repeated just after this treatment and demonstrated a new occlusion of the left intracranial internal carotid artery along with occlusion of a branch of the left external artery. The authors subsequently performed two-dimensional echocardiography and found a mobile thrombus in the left ventricle. In patients with intracardiac mobile thrombi, recombinant tissue plasminogen activator seems to accelerate breakup or detachment of the thrombi and subsequent recurrent embolization. Therefore, it seems better to pay attention to the presence of mobile intracardiac thrombus before commencing intravenous infusion of rt-PA. PMID- 8203777 TI - Arterial thrombophilia in primary thrombocythemia. A case report. AB - The clinical course of a case of primary thrombocythemia is described, complicated by a variety of recurrent and sequential thrombotic manifestations, involving the peripheral as well as the cerebrovascular and coronary microvasculature, demonstrating that thrombocythemia should be considered as an important risk factor for thrombosis, already at platelet count states in excess of 400 x 10(9)/L. PMID- 8203778 TI - Concurrent balloon dilation in a patient with mitral stenosis and coronary artery disease. A case report. PMID- 8203779 TI - At the crossroads of venous insufficiency and hemorrhoidal disease: Daflon 500 mg -repercussions of venous insufficiency on everyday life. AB - A research program has been developed to define an evaluation tool capable of assessing the impact of venous insufficiency and its treatments on the patient's everyday life. The methodology is described in the first part of this paper, followed by the results of the first phase of the research program, based on two surveys: a "qualitative" survey in a population of severely affected patients and a "quantitative" survey in a population of 150 patients. PMID- 8203780 TI - Venous investigations: the current position. AB - Chronic venous insufficiency (CVI) is a challenge to the medical profession, for clinical examination provides useful information on CVI, but it is qualitative and does not suffice, especially in patients with isolated deep venous insufficiency but without conspicuous signs of CVI. Ambulatory venous pressure (AVP) measurement has diagnostic value and prognostic capabilities, but it is invasive, is not suitable for repeated use in the same patient, and is not suitable as a screening test. The author surveys noninvasive, volumetric methods that correlate to AVP and that have been developed as alternatives. These include foot volumetry, photoplethysmography, light reflection rheography, ambulatory strain gauge plethysmography, and air plethysmography. The author discusses each with respect to technique, site of measurement, type of exercise used, parameters, correlation to AVP, clinical application, and predictive value. He also describes the tests' ability to determine presence or absence of disease, type of disease, and quantification of disease. PMID- 8203781 TI - Elements of a consensus on the therapeutic approach to thromboembolic disease. AB - A committee of twenty-nine international experts met at Windsor, England, during November 1991. Their purpose was to make recommendations on the current practice of prophylaxis against venous thromboembolic disease. This article is intended to provide a synopsis of some of the problems addressed at the meeting and the solutions proposed. It does not in any way replace the final consensus statement recently published. PMID- 8203782 TI - Pharmacologic properties of Daflon 500 mg. AB - AIMS AND METHODS: Some pharmacologic activities of a micronized flavonoid complex consisting of 90% diosmin + 10% hesperidin (Daflon 500 mg*) have been investigated by use of various experimental models: (1) interference with mechanisms of edema (synthesis of arachidonic acid derivatives, microvascular hyperpermeability induced by bradykinin, ischemia, or streptozotocin), (2) interference with lymphatic drainage (thoracic duct fistula in the dog). RESULTS: Daflon 500 mg inhibited prostaglandin E2 (PGE2) and thromboxane A2 (TxA2) synthesis during a one-month oral daily treatment (100 mg.kg-1.day-1) in the rat, after induction of chronic inflammation by subcutaneous implantation of sponge fragments. Microvascular hyperpermeability induced by bradykinin or ischemia in the rat cremaster muscle was reduced after an oral treatment with Daflon 500 mg (100 mg.kg-1 twice daily). Microvascular hyperpermeability of the streptozotocin induced diabetic rat was antagonized when Daflon 500 mg (300 mg.kg-1 once daily) was given orally as a preventive treatment. In the anesthetized dog, an increase in lymphatic flow, correlated with administered doses, was observed after IV injection of Daflon 500 mg. Lymphatic flow was maximal twenty minutes after injection of the drug (12.5 mg.kg-1) and was three times higher than the basal flow. CONCLUSION: The protective effect of Daflon 500 mg against the formation of perivascular edema and its therapeutic value in the treatment of venous stasis could be explained by its inhibitory activity on the inflammatory process or ischemia-induced hyperpermeability and by its stimulatory effect on the pulsatile activity of lymphatic vessels. PMID- 8203783 TI - Advantage of a micronized flavonoidic fraction (Daflon 500 mg) in comparison with a nonmicronized diosmin. AB - A randomized, double-blind, multicenter trial was performed to study the pharmacodynamic and clinical activities of Daflon 500 mg,* in comparison with a nonmicronized diosmin. Daflon 500 mg is a micronized purified flavonoidic fraction consisting of 450 mg of diosmin and 50 mg of hesperidin per tablet, which has been micronized in order to ensure a better gastrointestinal absorption. Ninety patients with chronic venous insufficiency of the lower limbs, stabilized for one year, entered the study. They received either two tablets of Daflon 500 mg or an equivalent dose of nonmicronized diosmin in two divided doses each day during two months. The following parameters were studied: functional clinical symptoms in the lower extremities, ankle circumference measurement, strain gauge plethysmographic parameters with 20, 40, and 60 mmHg venous occlusion, and clinical and biochemical acceptability. Statistically significant changes were obtained in both groups of patients in comparison with baseline values. However, the improvements in all clinical symptoms and plethysmographic parameters (maximum increase of venous volume at 60 mmHg and total time for emptying) were significantly better with Daflon 500 mg than with nonmicronized diosmin. The clinical and laboratory acceptability was similar in both groups. However, the percentage of satisfied patients was 95% in the Daflon 500 mg group, versus 80% in the nonmicronized diosmin group (p < 0.01). In conclusion, the pharmacodynamic and clinical activities of Daflon 500 mg are superior to those of an equivalent dose of nonmicronized diosmin and demonstrate the therapeutic advantage of a micronized formulation in the treatment of chronic venous insufficiency. PMID- 8203784 TI - The microcirculation in venous disease. AB - The author discusses three factors involved in venous ulceration: skin hypoxia, white-cell trapping, abnormalities in regulation of the microcirculation, eg, neuropathy. Leukocytes remain the most likely initiating factor. PMID- 8203785 TI - Techniques used to evaluate the cutaneous microcirculation: application of photoplethysmography to the assessment of a phlebotropic agent in the treatment of leg ulcers. AB - Over recent years, a number of functional investigations have been developed that allow a better evaluation of the physiology of the cutaneous microcirculation than that provided by the morphologic method. These investigations are also useful in pharmacologic studies. Following a review of the anatomy and physiology of the cutaneous microcirculation, the author presents the principal techniques of investigation and the results obtained with Daflon 500 mg* on the cutaneous microcirculation evaluated by photoplethysmography of the skin in patients with venous insufficiency and leg ulcers. PMID- 8203786 TI - Controlled studies of Daflon 500 mg in chronic venous insufficiency. AB - Although great advances have been made in the operative treatment of vascular disorders, the management of most venous problems is still nonsurgical. Daflon 500 mg* is a micronized flavonoid mixture of 90% diosmin and 10% hesperidin that has phlebotonic properties. The efficacy of Daflon 500 mg has been investigated in three double-blind, randomized trials using strain gauge plethysmography to provide quantitative information on venous hemodynamics in patients with chronic venous insufficiency. In total, 183 patients were treated with Daflon 500 mg versus a control group of equal number of patients. Daflon 500 mg produced a significant decrease in venous capacitance, venous distensibility, and venous emptying time (P < 0.001). In addition, these changes were accompanied by improvement in clinical symptoms and a decrease in the supramalleolar circumference. Clinical side effects were rare and led to treatment withdrawal in only 3 patients. It is concluded that Daflon 500 mg is of benefit to patients with chronic venous insufficiency. PMID- 8203787 TI - Mediators involved in inflammation: effects of Daflon 500 mg on their release. AB - Each step of an inflammatory reaction is triggered by one or several chemical or biological mediators such as arachidonic acid derivatives (prostaglandins [PG], leukotrienes [LT], or thromboxanes [TX]), vasoactive amines (histamine or serotonin), and oxygen free radicals (superoxide ion, O2-, or hydrogen peroxide, H2O2). In perivenous inflammation, these mediators play a prominent role in favoring vasodilatation (histamine), increasing membrane permeability (PGE2, histamine, free radicals) and providing a chemotactic signal for specialized cells, ie, neutrophil polynuclears, macrophages, lymphocytes (LTB4, free radicals). The antiinflammatory effects of Daflon 500 mg,* a micronized purified flavonoid fraction (90% diosmin, 10% hesperidin), were studied in different in vivo and in vitro models. In a model of inflammatory granuloma in the rat, Daflon 500 mg (100 mg/kg, orally) reduced edema formation and inhibited the synthesis for PGE2 (78.5%), PGF2 alpha (45.2%) and TXB2 (59.5%) (Damon et al, Arzneim Forsch/Drug Res 37:1149-1153, 1987). Intravenous injection of Daflon 500 mg (25 and 50 mg/kg) reduced the hyperglycemia induced by injection of alloxan in rat. This effect of Daflon 500 mg was linked to its ability to scavenge active oxygen radicals, demonstrated in vitro using human neutrophils (Lonchampt et al, Arzneim forsch/Drug Res 39:882-885, 1989) or mouse peritoneal macrophages (Bodinier et al, manuscript in preparation) stimulated by zymosan. The free radical scavenger effect of Daflon 500 mg is observed at concentrations ranging from 10(-7) M to 10(-4) M, with half-maximal effect between 10(-6) M and 10(-5) M. Thus, Daflon 500 mg behaves as a potent protective agent against inflammatory disorders. These properties may explain, at least in part, the clinical activity of Daflon 500 mg and justify its therapeutic use. PMID- 8203788 TI - Diagnosis and current treatment of hemorrhoidal disease. AB - Many new surgical and nonsurgical approaches to the treatment of hemorrhoids have been described: sclerotherapy, rubber band ligation, cryosurgery, anal dilatation, infrared photocoagulation, bipolar diathermy, and electrocoagulation. Which one is most effective depends on the size and degree of hemorrhoids, but surely depends as well on the experience of each proctologist. In the modern treatment, fast and painless procedures that can be carried out in the office practice under local anesthesia will be more and more indicated. PMID- 8203789 TI - Double-blind, placebo-controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute hemorrhoids. AB - One hundred patients with a history of hemorrhoidal disease and suffering from an acute hemorrhoidal attack were randomized into two parallel groups and treated with Daflon 500 mg* (D500) or placebo (PL) under double-blind conditions. Daflon 500 mg was administered at the dosage of three tablets bid the first four days and two tablets bid the following three days. Overall improvement of symptoms was greater in the D500 group than in the PL group, from D2 up to D7. The clinical severity of proctorrhagia, anal discomfort, pain, and anal discharge diminished in both groups but to a greater extent in the D500 group (P < 0.001 for all parameters except protorrhagia, P = 0.006). Inflammation, congestion, edema, and prolapse were more markedly improved in the D500 group than in the PL group. Duration and severity of the current hemorrhoidal episode, as assessed by patient self-evaluation, were less important in the D500 group as compared with previous episodes. Use of analgesics and topical medications diminished in both groups, with a major reduction in the D500 group from D4 (P < 0.001). Acceptability was good in both groups: no patient experienced major side effects. In summary, treatment with D500 resulted in a quicker and more pronounced relief of signs and symptoms of acute hemorrhoids than with the placebo. PMID- 8203791 TI - Safety and security of Daflon 500 mg in venous insufficiency and in hemorrhoidal disease. AB - Daflon 500 mg is a new flavonoid vasoprotector venotonic agent whose active principle is micronized and contains 90% diosmin and 10% flavonoids expressed as hesperidin. In animal studies, the safety of Daflon 500 mg is shown by an LD50 (lethal dose 50) of more than 3 g/kg, ie, 180 times the daily therapeutic dose, as well as by the absence of any toxic effect after repeated oral dosing for thirteen and twenty-six weeks, using a dose representing 35 times the daily dosage, in the rate and primate. Daflon 500 mg has no mutagenic action nor any significant effect on reproductive function. Gastrointestinal tolerance is good when administered orally in the rat. Transplacental passage and passage into breast milk are minimal. In the rat, 0.003% of the administered dose has been found in each fetus and 1% in breast milk. Clinical trials fulfill international scientific requirements and have collected more than 2850 patients treated with Daflon 500 mg at the dosage of two tablets per day for six weeks to one year. The proportion of patients with side effects (10% of those treated), essentially of a gastrointestinal or autonomic nature and leading to a rate of only 1.1% trial dropouts, is less than described in 225 patients given a placebo (13.9%) in controlled trials. Satisfactory clinical acceptability already confirmed in the short term was equally found in long-term treatment. Hemodynamic parameters (systolic and diastolic blood pressure) as well as laboratory parameters (hematology, liver and renal function, metabolic) were uninfluenced even by prolonged treatment for one year at the dosage of two tablets per day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203790 TI - Daflon 500 mg in the treatment of hemorrhoidal disease: a demonstrated efficacy in comparison with placebo. AB - Hemorrhoidal disease (HD) is a trophic disorder of the anal canal characterized by recurrent, self-resolving acute episodes. The author reports the results of a double-blind, placebo-controlled trial of the efficacy of Daflon 500 mg in the treatment of acute and chronic symptoms of hemorrhoids. One hundred and twenty outpatients (54 men, 66 women) suffering from an acute episode of HD during the previous two months were included. They received Daflon 500 mg (group D, n = 60) or placebo (group P, n = 60) two tablets daily for two months. The patients were examined at entry (T0) and at two months (T2). At T0, the two groups did not differ in terms of age, sex, weight, height, history of symptoms of HD; 7 patients were excluded from analysis because of treatment failure (group D, n = 2; group P, n = 3), or lost to follow-up (group P, n = 2). In group D, 40% of patients had an attack during the trial with a mean duration of 2.6 days and a mean severity of 1.1 scored on a scale from 1 to 3. These values were significantly different (P < 0.01) from the corresponding values in the P group: 70%, 4.6 days and 1.6 respectively. Each symptom and sign was scored on a scale of severity. The overall symptom score, scored from 0 to 15, decreased from 6.6 (group D) and 6.1 (group P) (NS) to 1.1 and 4.0 respectively (P < 0.01) at the end of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203792 TI - Applications of complement determinations in human disease. PMID- 8203793 TI - Macronodular pulmonary infiltrates in a patient with chronic asthma and productive cough. PMID- 8203794 TI - Serum immunoglobulins and IgG subclass levels in adults with chronic sinusitis: evidence for decreased IgG3 levels. AB - Serum immunoglobulin class and IgG subclasses were measured in 30 adult patients with chronic sinusitis documented by CT scans of the paranasal sinuses. Results were compared to 30 age-and-sex matched patients with chronic rhinitis who had normal sinus CT scans, and a matched group of asymptomatic, healthy subjects. None of the patients was taking oral corticosteroids and none had ever received allergen immunotherapy. IgA deficiency was present in 3% (2/60) of the patients with chronic rhinitis or sinusitis and IgG deficiency was seen in another two (3%). None of the normals had low IgA or IgG. Low levels of IgG1 or IgG3 were found in some patients in all three groups, while none had low IgG2 levels. Serum levels of IgG, IgA, IgM, IgG1, IgG2, and IgG4 were not significantly different between the groups. Mean serum IgG3 levels, however, were significantly lower in the chronic sinusitis group than the chronic rhinitis group (P < .003) or the normals (P < .0005). The incidence of below normal levels of IgG3 was also more frequent in chronic sinusitis than in chronic rhinitis (P < .04) or normals (P < .002). Patients in the chronic sinusitis group had a high incidence of asthma (57%) and atopy (45%) but there was no difference in immunoglobulin class or IgG subclass levels in matched asthmatics compared with nonasthmatic patients with chronic sinusitis. Atopic patients with chronic sinusitis had a higher frequency of IgG3 subclass deficiency than nonatopics (P = .04). Normalization of low immunoglobulin class or IgG subclass levels that coincided with clinical improvement was documented in two patients with sinusitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203795 TI - Immunoglobulin studies in children with inflammatory bowel disease. AB - Serum immunoglobulin A, and G subclasses were measured in patients with ulcerative colitis, Crohn's disease, and in normal controls. Significant differences were noted in elevated total gamma globulin in both disease groups: in elevated IgG1 in ulcerative colitis and elevated IgG2 in patients with Crohn's disease. These differences were not significantly related to disease activity in either disease although higher levels were observed in those with moderate and severe disease. PMID- 8203797 TI - Airway responsiveness to methacholine and risk of asthma in patients with allergic rhinitis. AB - To find out whether airway hyperresponsiveness is associated with a greater risk of asthma in subjects with allergic rhinitis, 66 nonasthmatic patients with allergic rhinitis underwent inhalation challenge with methacholine. Each patient was reevaluated prospectively at least once each year and a diagnosis of asthma was accepted if the subject developed episodic wheezing and/or cough plus airway obstruction and at least a 15% increase in FEV1 after inhaled salbutamol. Those subjects who developed asthma and ten individuals who did not develop asthma were rechallenged after the first asthma symptoms or at the end of the followup period, respectively. Risk of developing asthma during the followup period (mean of 43.8 months, range 36 to 70) was similar (P > .05) in those individuals who previously had airway hyperresponsiveness (2 of the 19 patients), when compared with subjects who were previously nonresponders (4 of the 47 patients). Further, in those subjects who developed asthma, geometric mean (range) PC20 decreased from 11.75 (0.40 to 50) during the initial evaluation to 1.66 (0.15 to 11.07) mg/mL after the first asthma symptoms (P < .05). No significant modifications of PC20 were detected in subjects who did not develop asthma. We conclude that a single determination of methacholine PC20 is not a reliable marker of the subsequent development of asthma in patients with allergic rhinitis. PMID- 8203796 TI - Comparative trial of acceptability of beclomethasone dipropionate and a new formulation of flunisolide. AB - A randomized, double-blind, crossover study of a new formulation of flunisolide nasal spray was performed comparing its acceptability and safety to that of aqueous beclomethasone dipropionate nasal spray. The single center study enrolled 100 adults with allergic rhinitis; of these, 99 provided valid data for analysis. Each study participant received a single dose of each study drug and assessed nasal burning/stinging and other adverse effects. Analysis of patient evaluations revealed no significant differences in nasal or pharyngeal irritation (P > .05); however, mild aftertaste was present with use of flunisolide (P = .059) compared with beclomethasone dipropionate. There was similar acceptance of both study drugs. PMID- 8203798 TI - Effect of electric heating carpet on house dust mites. AB - An electric heating carpet (EHC) that had been especially modified to produce a steady surface temperature of 45 to 50 degrees C was set up in the bedroom of an asthmatic patient, and the density of floor dust mites in this room was compared monthly for 2 years with that in two non-EHC control rooms. When the EHC was used during the mite-growing summer season, the monthly variation in mite density in the EHC room was almost parallel to that in the non-EHC rooms, with a preponderance of floor mites in the non-EHC rooms. In contrast, when the EHC was used during the winter season, the density of floor mites in the EHC room increased as compared with that in the non-EHC rooms, and the ratio of mite density in the EHC room to that in the non-EHC rooms was transiently reversed during this period. PMID- 8203799 TI - Bronchiolitis obliterans. PMID- 8203800 TI - Pubic itching due to food allergy. PMID- 8203801 TI - Text comprehension, memory, and learning. AB - People are often able to reproduce a text quite well but are unable to use the information in the text for other purposes. Factors that help people to reproduce a text have been studied for some time. This article explores ways that enable people to learn from texts. Content overlap between a text and the reader's prior knowledge is identified as one factor, and methods are proposed to identify whether a text is suitable for readers with given background knowledge. For readers with low background knowledge, a text should be as coherent and explicit as possible to facilitate learning. However, data are presented to show that for readers with adequate background knowledge, texts with coherence gaps that stimulate constructive activities are in fact better for learning. PMID- 8203802 TI - The course of adult intellectual development. AB - A program of research is summarized that represents the author's lifelong efforts to understand the adult life course of intellectual abilities. The Seattle Longitudinal Study has assessed mental abilities in more than 5,000 adults and has followed some for as long as 35 years. Integrative findings are provided on patterns and magnitudes of age changes, cohort differences, factor structure of mental abilities, antecedents for individual differences in aging trajectories, and interventions designed to remediate cognitive aging effects. PMID- 8203803 TI - Working with key players for psychological and mental health public services. AB - Key players must be located and identified in order to perform public service. For doing this, a model for organizing a societal mental health program, which includes the three agency categories of voluntary, official, and professional, is presented. It shows that psychologists can function in any community from local to international in each category. The author portrays some of the forces that turned him to public service. Then he cites his public service experience in various communities, such as the mental health association, the official mental health program, the psychological association, and the university. He identifies key players and explains methods of working with them. Finally, he summarizes some requisite skills for successful service activities. Primary among the skills are locating and relating to key community decision makers and understanding how the helping community functions. PMID- 8203804 TI - Engendering psychology. AB - Engendering psychology refers to cultivating a psychology that is sensitive to issues of gender and diversity. The increase in the number of female psychologists does not guarantee that the discipline will be responsive to those issues. This article reviews the progress made in engendering psychology by examining undergraduate textbooks and classroom instruction and looking at gender bias in both research and practice. By engendering psychology, it becomes a stronger science and profession and better serves the public interest. PMID- 8203805 TI - Does psychiatric disorder predict violent crime among released jail detainees? A six-year longitudinal study. AB - The authors examined whether jail detainees with schizophrenia, major affective disorders, alcohol or drug use disorders, or psychotic symptoms (hallucinations and delusions) are arrested more often for violent crimes six years after release than detainees with no disorders. Trained interviewers assessed 728 randomly selected male jail detainees using the National Institute of Mental Health Diagnostic Interview Schedule and then obtained follow-up arrest data for six years. Neither severe mental disorder nor substance abuse or dependence predicted the probability of arrest or the number of arrests for violent crime. Persons with symptoms of both hallucinations and delusions had a slightly higher number of arrests for violent crime, but not significantly so. These findings held even after controlling for prior violence and age. The findings do not support the stereotype that mentally ill criminals invariably commit violent crimes after they are released. Future directions for research are suggested. PMID- 8203806 TI - Reproductive rights and reproductive behavior. Clash or convergence of private values and public policies? AB - Using a rational scientific approach upholding public health values, this article notes experience gained from 25 years of cooperative transnational research on reproductive behavior. An overview of world population trends is followed by discussions of reproductive rights as a human right, the utility of acceptability studies of modern methods of fertility regulation, and findings from research on psychological responses to abortion, long-term developmental effects of compulsory pregnancy, and the use of incentives and disincentives to influence family size. There is also consideration of the clash between private values and public policy on reproductive behavior in the United States and the convergence achieved in Denmark and the Netherlands, where rates of unintended pregnancy are among the world's lowest. PMID- 8203807 TI - Pathology of olfactory mucosa in patients with Alzheimer's disease. AB - Characteristic changes that appear in the biopsied olfactory mucosa of patients with Alzheimer's disease (AD) were examined with immunohistochemical staining. Specimens were obtained from patients with clinical diagnoses of AD. Patients with vascular dementia and age-matched patients without dementia were used for controls. In most AD cases, neurofibrillary tangle-like abnormal tau protein (Tau) immunoreactivity was seen in the dendrites and perikarya of the olfactory receptor cells and in the nerve bundles. A senile plaque-like extracellular mass was found in the olfactory epithelium, and it reacted strongly to an anti-Tau antiserum and weakly to an anti-amyloid-beta protein antiserum. Ubiquitin (Ubq) immunoreactivity was also observed in the dendrites. Tau immunoreactivity of the perikarya and extracellular mass, and Ubq immunoreactivity were especially characteristic of the olfactory mucosa of AD patients. From these results, it is clear that the same pathologic changes in the brain are also present in the olfactory mucosa of patients with AD. Not only disruption of the central olfactory pathway, but also an olfactory disturbance of AD patients is caused by peripheral changes. Furthermore, an olfactory mucosal biopsy could be a useful method for a definitive diagnosis of AD. PMID- 8203808 TI - Nonsyndromic hearing loss: an analysis of audiograms. AB - We examined features of the audiograms of 136 individuals, from 28 families, affected by nonsyndromic genetic hearing loss. There were 83 (12 families) with autosomal dominant (AD) loss, 50 (15 families) with autosomal recessive (AR) loss, and 3 (1 family) with X-linked recessive loss. The main audiogram shapes found were sloping (50.3%), residual (26.5%), and flat (21.0%). Specific shapes (ascending and U-shaped) only occurred in 3.7% of AD cases. Audiogram shapes were found to be significantly different between AD and AR families, and showed intrafamilial and interfamilial variability. In the AR group, the main shapes were residual and sharply sloping, and in the AD group, sharply sloping, flat, and gently sloping. There was a significant difference in the degree of hearing loss between AD and AR types, with AD being milder than AR. It has been shown that there is more marked intrafamilial variation in the degree of hearing loss in AD families than in AR ones. The results suggest that the audiograms of nonsyndromic hearing loss are usually nonspecific and that counseling of family members would be better based on the specific family's condition rather than on group information. PMID- 8203809 TI - Preliminary report on L-forms: possible role in the infectious origin of secretory otitis media. AB - Infection and inflammation of the middle ear cleft are important factors in the pathogenesis of secretory otitis media. Although high percentages of negative cultures are confronted in many studies, strong evidence pointing to the infectious nature of this disease could not be overlooked. Many authors agree about the failure of conventional culture methods in identifying the responsible pathogen or pathogens. Besides, some agents, such as some kinds of antibiotics, lysozyme, and perhaps some undetected materials, are capable of changing bacterial behavior and consequently the clinical course. Effusions taken from 40 ears with secretory otitis media were cultured by means of conventional brain heart infusion broth and special hypertonic thioglycollate broth. Strikingly, bacterial L-forms were detected in 6 specimens in thioglycollate broth, with no growth in the conventional broth. We concluded that these atypical forms of bacteria, the L-forms, may play an important role in the bacteriologic aspect of secretory otitis media. PMID- 8203810 TI - Transformation of mucosal secretory elements in chronic maxillary sinusitis after endoscopic sinus surgery. AB - To evaluate the secretory element transformation of maxillary sinus mucosa after endoscopic sinus surgery (ESS), I enrolled 20 patients. Five normal antral mucosae were used as controls, and 15 antral mucosae were investigated according to pathologic and secretory patterns. The post-ESS mucosa was evaluated at the 16th week, when gross recovery appeared. Specimens from the rear wall of the antrum were observed under a scanning electron microscope (x2,000). A significant decrease of goblet cells and increase of glands was illustrated in the sinusitis cases, especially the polypoid and purulent groups. In post-ESS cases, the number of goblet cells is about the same as in controls, but the number of gland openings is higher. My conclusions were that 1) the repair of the antral mucosa requires more time than gross recovery and 2) post-ESS follow-up should be longer than 16 weeks to prevent recurrence. PMID- 8203811 TI - Indium 111-labeled white blood cell scintigraphy as an unreliable indicator of malignant external otitis resolution. AB - The field of otolaryngology-head and neck surgery has seen many advances in the treatment and prognosis of malignant external otitis (MEO). However, establishing the resolution of the infection remains problematic. A recent report suggests that indium 111-labeled white blood cell scintigraphy may be a reliable and timely indicator of resolution of infection. We present a case of a false negative white blood cell scan in a patient with persistent MEO. A discussion of this case and a review of the literature illustrate that there continues to be no "gold standard" for establishing MEO resolution. PMID- 8203812 TI - Changes in immunostaining of cochleas with experimentally induced endolymphatic hydrops. AB - Cochleas with experimentally induced endolymphatic hydrops were immunostained for Na+,K(+)-ATPase, intracellular Ca(++)-ATPase, carbonic anhydrase, aldehyde dehydrogenase, calcium-binding proteins, vimentin, and the gap junction protein, connexin 26. No changes in immunostaining of hydropic ears were observed 1 week after blockage of the endolymphatic duct. Two weeks to 1 month after the operation, immunostaining of type I fibrocytes in the spiral ligament, which are positive for all but Na+,K(+)-ATPase, was slightly decreased on the operated side. These changes became more pronounced 3 months after the operation. However, staining for Na+,K(+)-ATPase of the stria vascularis and of type II fibrocytes of the spiral ligament was not reduced until 6 months postoperative. The reduction of enzymes and other cell constituents that may be involved in ion balance of cochlear fluids indicates that cells in the spiral ligament play an important role in cochlear homeostasis and that they merit further study in animal and human otopathology. PMID- 8203813 TI - Statistical model estimating the occurrence of otitis media from temporal bone pneumatization. AB - In order to investigate the relationship between the pneumatization of temporal bones and the occurrence of otitis media in Greenlandic Inuit, 36 Greenlandic Inuit were examined by radiography of the temporal bones. The pneumatized cell area was measured planimetrically. All subjects answered a questionnaire on infectious middle ear disease (IMED), and an objective otologic examination was performed. Nine persons of 34 (26%) reported IMED in childhood, and there was IMED reported in all pneumatized areas below 400 mm2. Based on bilateral area measures, a polychotomous logistic regression model was applied. The occurrence of IMED was shown to be associated with smaller areas, and unilateral IMED was associated with pronounced asymmetry. The model has enabled risk assessment, and 8 persons were designated by the model as having had IMED with a sensitivity of 67% (confidence interval 30% to 93%) and a specificity of 92% (confidence interval 74% to 99%). When the model was applied to a historical anthropological Inuit material from 1700 to 1800 AD, 6 of 56 crania were designated as having had IMED. This method has improved the accuracy of estimating the occurrence of IMED in ancient populations. PMID- 8203814 TI - Electrocochleography with postural changes in perilymphatic fistula. Animal studies. AB - The present study investigated the effect of altering body position on electrocochleographic findings in the presence and absence of perilymphatic fistula. Three groups of guinea pigs included 1) 10 normal control animals, 2) 10 experimental animals with induced perilymphatic fistula, and 3) 10 control animals with induced perilymphatic fistula. In the first two groups, animals were successively tested in three positions: first with the ventral aspect down, again after 30 minutes with the test ear up, and again after 15 minutes with the test ear down. In the third group, body position was not altered. Stimuli consisted of clicks and 6,000-Hz tone bursts. Data analysis included summating potential (SP) amplitude, action potential (AP) amplitude, and AP threshold for the click stimuli. Only the normal control group showed a significant effect of body position for the SP/AP amplitude ratio. Average change was greater in the experimental group, but high variability precluded statistical significance. Both fistulized animal groups exhibited high variability in the SP/AP amplitude ratio, with and without postural change. The SP/AP amplitude ratio and SP amplitude were significantly larger for the two fistulized groups than for the normal control group. No significant change in threshold occurred across positions for any group. PMID- 8203815 TI - William Wright, aurist: nineteenth century pneumatic practitioner and a discoverer of anesthesia. AB - William Wright (1773-1860) was Surgeon-Aurist in Ordinary to Her Majesty Queen Charlotte of England. One interesting feature of his otologic practice was his employment of gases and vapors in treating deafness and other disorders of the ear. Among aeroform substances that he advocated for such uses were nitrous oxide and ether--gases that were destined to become anesthetic agents in another quarter of a century. Wright made the observation that inhalation of ether vapor would suppress the cough elicited by instrumentation of an inflamed and sensitive ear canal. He used ether inhalation beginning about 1820 in his practice for this purpose, and in so doing appears to have administered some of the earliest anesthetics on record. PMID- 8203816 TI - Diagnosis of cavernous sinus thrombosis by magnetic resonance imaging using flow parameters. PMID- 8203817 TI - Osteomyelitis of the mandible simulating a Stafne mandibular cortical defect. PMID- 8203818 TI - Lichen planus and lichenoid lesions of the oral cavity. AB - Lichen planus is a mucocutaneous disease of unknown cause that has its principal clinical manifestations in the skin and mucosa of the oral cavity. The natural history of the cutaneous form is one of spontaneous resolution over time, while oral lichen planus pursues a much more chronic course with a low order of resolution. Oral lichen planus must be distinguished from lichenoid lesions, including lichenoid dysplasia. Malignant change in oral lichen planus is rare and is prompted by carcinogenic cofactors. There is no increased risk of development of carcinoma in cutaneous lichen planus. PMID- 8203819 TI - Serum analyte pattern characteristic of fulminant hepatic failure. AB - Fulminant hepatic failure (FHF) is a poorly understood condition in which total liver failure occurs and is thought to be caused by a variety of conditions including Reye's syndrome, hepatitis, drug overdoses, and vascular insufficiency. While this condition is an uncommon one, it carries with it a high fatality rate and must therefore be diagnosed as rapidly as possible. Six patients have been observed over a two-year period with biopsy and/or autopsy-confirmed FHF: one with acute hepatitis B-delta; three with histories of alcoholism, two of them with cirrhosis; one with acute tylenol overdose; and one with hepatic vascular insufficiency. All of these patients, except one, exhibited a rapid, fatal downhill course after onset of symptoms. In all of these patients, a consistent elevation was observed in serum levels of aspartate aminotransferase (AST) or serum glutamate oxaloacetate transaminase (SGOT) and alanine aminotransferase (ALT) or serum glutamate pyruvate transaminase (SGPT) such that the ratio of AST to ALT was significantly greater than 1 and in serum levels of ammonia. Other liver function tests were found to be abnormal but not in so consistent a pattern, although total protein and albumin were found to be significantly decreased in all of these patients. The stereotypical elevation of the transaminases with high AST-to-ALT ratios and the rise in ammonia appear to characterize this life-threatening illness most reliably. PMID- 8203820 TI - Analytical evaluation of methods for serum creatine kinase-MB. Electrophoresis, immunoinhibition and solid phase separation. AB - The purpose of this study was to evaluate immunoassay methods for the measurement of serum cardiac creatine kinase isoenzyme (CK-MB) with respect to sensitivity and specificity. The CK-MB electrophoretic assay (Helena Laboratories) was used as the reference. Two principles of immunoassay were included in the evaluation,- immunoinhibition and solid phase separation. The direct immunoinhibition techniques were from Beckman Instruments (CKMB reagent) and DuPont Medical Products (CKMB). Three solid phase separation techniques were from Abbott Laboratories (IMx CKMB), DuPont (acaPlus MCKMB), and Tosoh Medics Inc. (AIA-Pack CKMB). The electrophoretic method for separation of the CK isoenzymes has good specificity but lacks sensitivity for CK-MB in low concentrations. The immunoinhibition methods lack specificity and correlate poorly with the electrophoresis method and with the solid phase methods. The solid phase separation techniques are highly sensitive and show an excellent correlation with electrophoresis when based on specificity. The solid phase separation methods correlate well with each other. PMID- 8203821 TI - Prevention of cisplatin-induced toxicity by selected dithiocarbamates. AB - Cisplatin (CDDP) is a widely used antineoplastic agent, the administration of which is associated with dose-related toxicities. Currently, ototoxicity is the dose-limiting toxicity of cisplatin and difficult to prevent. The purpose of this study was to determine the ability of two substituted dithiocarbamates, diethyldithiocarbamate (DDTC) and N-methyl-D-glucaminedithiocarbamate (NMGDTC) to abrogate cisplatin-induced toxicity in young female Hartley albino guinea pigs. The animals were divided into saline controls, CDDP only, NMGDTC only, and CDDP DDTC or CDDP-NMGDTC combinations with DDTC or NMGDTC given 30 minutes before or 30 minutes after CDDP. Auditory brainstem responses (ABR) were recorded periodically in sound-attenuated rooms to assess hearing thresholds. Representative cochleas were harvested at autopsy, processed, and examined by scanning electron microscopy (SEM). The NMGDTC produced marked reduction of CDDP induced ototoxicity and weight loss. No significant ABR shift was found regardless of the order of CDDP and NMGDTC administration, but the derivative was more effective in preventing anorexia and weight loss when given prior to CDDP. Specifically, groups of guinea pigs given NMGDTC prior to CDDP showed the only weight gain among the treatment groups. Diethyldithiocarbamate, the other dithiocarbamate evaluated in this study, did not provide protection from cisplatin ototoxicity regardless of the order of administration. A CDDP-induced weight loss was reduced when DDTC was administered prior to CDDP. In summary, NMGDTC given prior to CDDP offers remarkable protection against cisplatin-induced ototoxicity and weight loss. It may help eliminate dose-limiting cisplatin induced toxicity and allow the use of cisplatin at higher doses in cancer chemotherapy. PMID- 8203822 TI - Chemical pathology of homocysteine. III. Cellular function and aging. AB - The homocysteine thiolactonyl derivative, thioretinaco ozonide, is believed to function as an electron acceptor in oxygen metabolism and as the binding site for adenosine triphosphate (ATP) synthesis by mitochondria, preventing damage by free radical oxidants in resting cells. During cell division, methionine is converted to homocysteine thiolactone, converting thioretinaco to thioco, increasing free radical oxidants, and oxidizing cellular glutathione and ascorbate. Homocysteic acid has growth hormone activity and releases insulin-like growth factor in hypophysectomized rats, promoting oxidation of homocysteine thiolactone to sulfated glycosaminoglycans of cartilage. The free base of homocysteine thiolactone produces keratinization, squamous metaplasia, dysplasia, and carcinogenesis in normal mouse tissues. The efficiency of homocysteine thiolactone metabolism declines with aging, explaining decreased formation of adenosyl methionine in aging and suggesting loss of thioretinaco ozonide from membranes of aging cells. The effects of aging on enzyme activity, connective tissues, lipid synthesis, auto-immune diseases, atherogenesis and carcinogenesis are related to these changes in homocysteine metabolism. PMID- 8203824 TI - Self-care myth reconsidered. PMID- 8203823 TI - Fluorescent in situ hybridization as an adjunct to conventional cytogenetics. AB - Fluorescent in situ hybridization (FISH) is a molecular cytogenetic technique that exploits the availability of recombinant deoxyribonucleic acid (DNA) technology. In metaphase FISH, a specific nucleic acid sequence (probe) is bound to the homologous segment on a metaphase chromosome in a fixed preparation on a glass slide. The presence of a region-specific DNA sequence in a nondividing cell can be detected using interphase FISH. Interphase cytogenetics via FISH can be performed on fixed cells harvested during a routine culture, on tissue sections and on many cytologic specimens. Specific examples of clinical and research applications are discussed to illustrate the utility of FISH in the detection of constitutional and acquired chromosomal abnormalities. PMID- 8203825 TI - Populations at risk: where do we stand? PMID- 8203826 TI - Economic impoverishment as a health risk: methodologic and conceptual issues. AB - Although economic impoverishment has long been recognized as a health risk, it has not generally been targeted as a modifiable risk factor. A number of methodologic and conceptual issues have impeded and obscured explanation of the nature and characteristics of the relationship between socioeconomic status and health. Further investigation is needed to address directional effects, confounding factors, and measurement difficulties. Conceptual representations of the links between economic impoverishment and health need to be clarified and expanded. Until this relationship is better understood, development of effective strategies to improve health for the economically disadvantaged will be problematic. PMID- 8203827 TI - The paradox of HIV/AIDS as expanding consciousness. AB - A heuristic approach employing Newman's method for pattern identification was used to examine the theory of health as expanding consciousness in persons with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Themes derived from the interview of nine gay men portrayed a pattern of alienation during childhood, followed by a breaking away from family, and progressing to cycles of aloneness and searching. Recognition of HIV/AIDS in their lives brought them to a turning point of more meaningful connectedness. This pattern is viewed as expanding consciousness and possibly a phenomenon of cultural evolution. PMID- 8203828 TI - Circles of care: home care and community support for rural older adults. AB - Rural dwelling, frail older adults are a vulnerable population owing to the complexity of health problems superimposed upon limited health care resources. Home care facilitates managing complex health needs and is congruent with rural valued independence. An ethnography was conducted to describe rural home care for frail older adults from the perspective of those delivering and receiving services. A major theme identified was "Circles of Care." Grounded in rural culture, the circles assisted the system of formal care to work in harmony with informal care, maintaining independence for vulnerable rural elderly and their families. PMID- 8203829 TI - How lesbians recognize and respond to alcohol problems: a theoretical model of problematization. AB - To determine how one specific at-risk population problematizes alcohol use and responds to alcohol-related difficulties, findings from an ethnographic interview study of lesbians recovering from alcohol problems were used to develop a theoretical model of problematization. Problematization consists of two phases: recognition and response. Recognition involves problem indicators varying by type (cumulative vs immediate) and source (personal vs environmental). Movement from recognition to response is hindered by perceptual and environmental constraints. Response consists of interrelated processes of construction, interaction, action, and validation. On the basis of validation, problems are reconstructed and new problems are recognized as the cycle continues. PMID- 8203830 TI - Cultural themes in family stress and violence among Cambodian refugee women in the inner city. AB - Cambodian refugee women frequently face the cumulative trauma of war experiences and cultural adaptation to the American inner-city environment. This qualitative study investigated cultural beliefs, coping strategies, and management of family stress among Cambodian refugee women living in the inner-city environment. Focused and open-ended interviews were conducted in the informants' homes using the Cambodian language. Stressful and violent events were managed by nonconfrontation and withdrawal. These two themes are hypothesized as the culturally identified means by which inner-city Cambodian refugee women control and harmonize situations of stress. Further study is needed to develop the theoretical base for developing culturally sensitive nursing intervention strategies with this high risk population. PMID- 8203831 TI - Health care dilemmas for women with serious mental illness. AB - Women with serious mental illness are a population at risk because of their invisibility. A comprehensive and critical literature review documents the issues and gaps in this aspect of the health care environment for women. A conceptual model outlines the current health-related risks for women with serious mental illness. Use of a feminist perspective challenges the underlying assumptions and opens new arenas for research and practice. The speculative, theoretical context thus created encourages and supports the questioning process that is the precursor to change. PMID- 8203832 TI - Colonization resistance. PMID- 8203833 TI - Cefepime compared with ceftazidime as initial therapy for serious bacterial infections and sepsis syndrome. AB - In an open randomized multicenter comparative study, we evaluated the safety and efficacy of cefepime (CP; 2.0 g given intravenously every 12 h) and ceftazidime (CZ; 2.0 g given intravenously every 8 h) as initial treatment for adult patients with suspected serious bacterial infections. A total of 133 patients entered the study, of whom 114 were evaluable for clinical and microbiological response assessment: 56 received CP and 58 received CZ. About 50% (30 who received CP and 25 who received CZ) fulfilled the criteria of the sepsis syndrome. The treatment groups were comparable with respect to sex distribution, mean age, underlying diseases, treatment duration, APACHE II score, and type of infection. The most commonly cultured microorganisms were members of the family Enterobacteriaceae, Streptococcus pneumoniae, and Staphylococcus aureus. The causative microorganisms were eradicated from 92% (37 of 40) of patients with a microbiologically documented infection who underwent treatment with CP; they were eradicated from 86% (42 to 49) of patients who received CZ. The responses of only clinically documented infections in the CP group were 90% (27 of 30 patients); in the CZ group they were 87% (26 of 30 patients). When patients fulfilled the criteria of the sepsis syndrome (septic shock excluded), the causative microorganisms were eradicated from 89% (16 of 18) of CP-treated patients and 86% (12 of 14) of CZ treated patients. None of these differences was statistically significant. Mortality was the same in both groups (four patients in each group) and was not attributable to the study medication. In conclusion, CP is at least as effective and as safe as CZ, as initial antimicrobial therapy for suspected serious bacterial infections in nonneutropenic patients with or without the sepsis syndrome. CP has the additional advantage in that it can be given twice daily, which may lead to a decrease in hospital costs. PMID- 8203834 TI - Activity of Bay y3118 against quinolone-susceptible and -resistant gram-negative and gram-positive bacteria. AB - The activity of Bay y3118 against laboratory strains of bacteria, including those with mutations in gyrA, with decreased expression of outer membrane proteins, and/or that are multiply resistant, and 121 selected clinical isolates, including highly fluoroquinolone-resistant bacteria from Spain and Argentina, was determined. Bay y3118 was extremely active (MICs, < or = 1 microgram/ml) against all bacteria, including quinolone-resistant laboratory strains. However, Bay y3118 was less active against 46 of 121 quinolone-resistant clinical isolates, such that > or = 16 micrograms of Bay y3118 per ml was required to inhibit 3 isolates. The concentration of Bay y3118 required to inhibit DNA synthesis by 50% correlated well with the MIC. Bay y3118 had accumulation kinetics similar to those of previously studied fluoroquinolones, e.g., ciprofloxacin, and there was a 50% decrease in the steady-state concentration in those members of the family Enterobacteriaceae that lacked porin proteins. Magnesium chloride at 20 mM apparently abolished the accumulation of Bay y3118 into Escherichia coli and reduced the level of accumulation into other gram-negative bacteria and Staphylococcus aureus. Carbonyl cyanide m-chlorophenylhydrazone at 100 microM enhanced the accumulation of Bay y3118 into E. coli, but it had a minimal effect on accumulation into S. aureus. PMID- 8203835 TI - In vivo activities and penetration of the two components of the streptogramin RP 59500 in cardiac vegetations of experimental endocarditis. AB - We evaluated the in vivo activity and the diffusion of radiolabelled RP 57669 (RPI) and RP 54476 (RPII), the two components of the injectable streptogramin RP 59500, alone or in combination, in aortic vegetations from experimental endocarditis in rabbits. RPI and RPII demonstrated in vitro bacteriostatic and bactericidal synergy against a clinical strain of Staphylococcus aureus resistant to methicillin and susceptible to erythromycin. In experimental staphylococcal endocarditis, RP 59500 was as effective as vancomycin and significantly more effective than RPI (P < 0.01) and RPII (P < 0.05). Autoradiography studies showed different patterns of distribution into cardiac vegetations infected with Streptococcus sanguis for [14C]RPI and [14C]RPII. [14C]RPI was homogeneously distributed throughout the vegetations whereas [14C]RPII showed a decreasing gradient of concentration between the periphery and the core of the vegetation, with an approximately 2:1 ratio. [14C]RPI diffused approximately 2 to 4 times more than [14C]RPII into the core of the vegetations. Since the injected ratio of RPI and RPII is 30:70 in RP 59500, the actual RPI:RPII ratio in the core of the vegetation may range from 0.8 to 1.7, a ratio which remains compatible with the in vivo synergism demonstrated between the two components. PMID- 8203836 TI - Inhibition of intracellular growth of Listeria monocytogenes by antibiotics. AB - We studied the activities of 15 antibiotics on the intracellular growth of Listeria monocytogenes in a HeLa cell line. After 24 h of contact with the infected cells, the antibiotics most effective against the intracellular growth of the 10 strains tested were amoxicillin, temafloxacin, and sparfloxacin, which nevertheless failed to totally eliminate the intracellular bacteria. Rifampin and co-trimoxazole had variable effects, depending on the isolates studied. The most active combinations were amoxicillin-sparfloxacin, co-trimoxazole-gentamicin, and sparfloxacin-co-trimoxazole. The results suggest the value of using a cell culture technique to study the activities of antibiotics against certain bacteria with intracellular sites of multiplication. PMID- 8203837 TI - Multiple-dose pharmacokinetics of sparfloxacin and its influence on fecal flora. AB - In a randomized, double-blind, placebo-controlled, multiple-dose pharmacokinetic study, the safety and effect on intestinal flora of sparfloxacin (SPX) were determined in 12 healthy male volunteers (8 received SPX and 4 received a placebo). Following fasting and oral administration of 400 mg on day 1 and 200 mg on days 2 to 8, concentrations of the free drug in serum, urine, and feces were measured by high-performance liquid chromatography; serum and urine were also evaluated by a microbiological assay. All results, except those for renal excretion, exclude the glucuroconjugate metabolite. A mean peak concentration in serum (400-mg dose) of 0.56 +/- 0.13 mg/liter was measured 3.52 +/- 0.98 h after administration. Pharmacokinetic parameters (measured by high-performance liquid chromatography) were based on an open, one-compartment model and resulted in the following day 1 (calculated for the 200-mg dose), day 4 (recalculated for a single dose), and day 8 values (mean +/- standard deviation): area under the curve, 16.4 +/- 2.3 (day 1) and 18.3 +/- 5.1 (day 4) mg.h/liter; elimination half life, 18.3 +/- 3.9 h; steady-state volume of distribution, 4.7 +/- 1.4 (day 1) and 4.3 +/- 1.2 (day 8) liters/kg; apparent total clearance, 201 +/- 31 (day 1) and 190 +/- 51 (day 4) ml/min; renal clearance, 19.1 +/- 5.8 (day 1) and 23.2 +/- 19.4 (day 4) ml/min. Recovery in urine on day 1 was 5.89% +/- 1.4% of the dose in 24 h for the parent compound and 18.4% +/- 6.8% for the SPX glucuronide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203839 TI - Alterations in peptidoglycan precursors and vancomycin susceptibility in Tn917 insertion mutants of Enterococcus faecalis 221. AB - Derivatives of the highly vancomycin-resistant Enterococcus faecalis strain 221 (MIC, 1,024 micrograms/ml) harboring Tn917 insertions in vanR, vanH, and vanA were compared with the parent strain and the susceptible plasmid-free strain JH2 2 (MIC, 2 micrograms/ml). Cytoplasmic pools of UDP-N-acetyl-muramyl-peptide precursors of strain 221 contained the depsipeptide-terminating precursor as well as elevated levels of both the tripeptide and tetrapeptide precursors. Insertional inactivation of vanR resulted in the loss of carboxypeptidase activity, full susceptibility to vancomycin, and precursor pools similar to those of JH2-2. For the vanA insertional mutant the MBC of vancomycin was fourfold higher than that for JH2-2, and the mutant had increased levels of tripeptide and tetrapeptide precursors compared with those for JH2-2. The vanH insertional mutant showed elevated levels of these precursors, as well as a small amount of depsipeptide, and both the MIC and the MBC of vancomycin were increased compared with those for JH2-2. These findings suggest that DD-carboxypeptidase activity, under the control of vanR, results in increased pools of both tripeptide and tetrapeptide precursors, which may contribute to survival in the presence of vancomycin. PMID- 8203838 TI - A randomized trial of roxithromycin in patients with acute leukemia and bone marrow transplant recipients receiving fluoroquinolone prophylaxis. AB - Fluoroquinolone prophylaxis in patients with profound neutropenia may be useful for preventing gram-negative bacterial infection, but it is ineffective against gram-positive bacterial infections in the bloodstream, particularly those caused by streptococci and coagulase-negative staphylococci, which appear to have emerged as significant causes of morbidity, decreased treatment efficacy, and the increased costs of empiric antimicrobial therapy. In a prospective, randomized, open trial, we evaluated the efficacy and safety of oral roxithromycin (150 mg twice daily) as additional antibacterial prophylaxis in 131 adult patients with acute leukemia and bone marrow transplant recipients receiving oral ofloxacin. In comparison with patients given ofloxacin alone, fewer patients receiving ofloxacin plus roxithromycin developed bacteremia caused by viridans group streptococci (incidence, 9 versus 0%; P = 0.03), while the incidence of bacteremia caused by other organisms, the incidence of febrile episodes from any cause, the risk of infection-associated complications (including prolonged or secondary fever, pneumonia, septic shock, need for mechanical ventilation, and/or infection-related death), and antimicrobial usage for therapy were comparable between both groups. Adverse events possibly related to the study drugs were slightly more common among the patients receiving the combination treatment (P = 0.05). Although effective for the prevention of streptococcal bacteremia, the addition of roxithromycin to a fluoroquinolone should not be used routinely as a prophylactic regimen in patients with profound neutropenia, but it might be considered and may be useful for cancer patients with a particularly high risk of streptococcal infection and related complications. PMID- 8203840 TI - Susceptibility of Plasmodium falciparum to a combination of thymidine and ICI D1694, a quinazoline antifolate directed at thymidylate synthase. AB - Unlike mammalian cells, malarial parasites lack the enzymes to salvage preformed pyrimidines. For this reason, a combination of a thymidylate synthase inhibitor and the nucleoside thymidine should provide selective antimalarial activity even in the absence of any known active site differences between malarial and mammalian thymidylate synthases. To test this hypothesis, we evaluated the in vitro antimalarial activity of ICI D1694, a quinazoline antifolate that inhibits thymidylate synthase in mammalian cells. ICI D1694 inhibited the in vitro proliferation of Plasmodium falciparum with a 50% inhibitory concentration of 20 microM. As predicted, this antimalarial activity was not affected by the presence of 10 microM thymidine in the culture medium. In contrast, five different mammalian cells, several of which were susceptible to nanomolar levels of ICI D1694 in the absence of thymidine, were rescued by thymidine. At doses of 100 microM ICI D1694 and 10 microM thymidine, the proliferation of parasites was completely inhibited, but the proliferation of all mammalian cells remained unaffected. A test of susceptibility patterns among five different isolates of P. falciparum revealed that strains resistant to pyrimethamine, cycloguanil, or chloroquine had susceptibilities to ICI D1694 essentially the same as those of wild-type parasites. These findings are consistent with the hypothesis that, intracellularly, ICI D1694 inhibits P. falciparum thymidylate synthase. Overall, it is clear that even with an inhibitor of malarial thymidylate synthase that is not particularly effective in itself, one can obtain selective inhibition of parasites if the antimalarial agent is used in combination with thymidine. More effective inhibitors of malarial thymidylate synthase will undoubtedly lead to selective chemotherapy in vivo. PMID- 8203841 TI - Assessment of a fluoroquinolone, three beta-lactams, two aminoglycosides, and a cycline in treatment of murine Yersinia pestis infection. AB - Amoxicillin, cefotaxime, ceftriaxone, gentamicin, doxycycline, and ofloxacin were active in vitro, like the reference drug streptomycin, against the virulent strain Yersinia pestis 6/69M. The comparative efficacies of these drugs in vivo were evaluated in a standardized and reproducible mouse model of systemic infection. Each antibiotic was injected intravenously once, at 24 h postinfection, and then repeatedly during 48 h. In vivo results were measured by counting the viable bacteria recovered from the whole spleens of mice sacrificed at selected times. All the drugs were manifestly successful; ceftriaxone, ofloxacine, and the reference drug were the most effective. Therefore, gentamicin and doxycycline could be used, depending on the clinical forms of the Y. pestis infection. Further investigations on beta-lactams, especially those used in the present study, could be carried out to confirm or not confirm their activities against Y. pestis. Ofloxacin appeared to be as active and to perform as rapidly as streptomycin in the treatment of murine Y. pestis infection, which is in agreement with the previous successes obtained with the use of fluoroquinolones in the treatment of murine infections caused by other pathogenic yersiniae. PMID- 8203843 TI - Effect of hyperproduction of TEM-1 beta-lactamase on in vitro susceptibility of Escherichia coli to beta-lactam antibiotics. AB - The susceptibility of 173 TEM-1-producing isolates of Escherichia coli was assessed by determination of MICs by the agar dilution method. MICs of amoxicillin, mezlocillin, cephaloridine, and, to a smaller extent, amoxicillin clavulanic acid (but not cephalexin, cefuroxime, cefotaxime, ceftazidime, or imipenem) were higher for isolates that produced large amounts of beta-lactamase than for isolates that produced smaller amounts. The effect of fixed concentrations of clavulanic acid on resistance to amoxicillin was assessed for 34 selected TEM-1-producing isolates. Low concentrations of the inhibitor (0.5 to 1 microgram/ml) reduced the amoxicillin MICs substantially for almost all the isolates, although the reductions were not sufficient to render any of the isolates amoxicillin susceptible. Higher concentrations of clavulanic acid had progressively greater effects on amoxicillin MICs, but even at 8 micrograms/ml some of the isolates with high beta-lactamase activities remained resistant or only moderately susceptible to amoxicillin. All the isolates were inhibited by clavulanic acid (in the absence of amoxicillin) at concentrations of 16 to 32 micrograms/ml. TEM-1 beta-lactamase activity was inhibited in vitro by clavulanic acid, but not totally, with approximately 2% of the initial activity remaining at 2 micrograms/ml and 0.4% remaining at 8 micrograms/ml. These findings suggest that the amount of beta-lactamase activity is a major determinant of the degree of resistance to several beta-lactam antibiotics and can make the difference between susceptibility and resistance to some compounds, notably the combination of amoxicillin with clavulanic acid. PMID- 8203842 TI - Role of tolerance in treatment and prophylaxis of experimental Staphylococcus aureus endocarditis with vancomycin, teicoplanin, and daptomycin. AB - The role of Staphylococcus aureus tolerance in the treatment and prophylaxis of endocarditis in rats was investigated. The efficacies of vancomycin, teicoplanin, and daptomycin, alone and in combination with rifampin, were compared in rats with endocarditis infected with a tolerant strain of S. aureus and in rats with endocarditis infected with its nontolerant variant. In vitro the cloxacillin tolerant strain was also tolerant to vancomycin and teicoplanin, but not to daptomycin. However, tolerance to these antibiotics did not influence the results of treatment of experimental S. aureus endocarditis. There was no difference in the bacterial densities in the vegetations of rats infected with either the tolerant or the nontolerant strain after 5 days of treatment with any of the antibiotic regimens. Of all antibiotics, daptomycin was the most effective in reducing bacterial numbers in vegetations. Combination of rifampin with vancomycin or teicoplanin improved the results of treatment for the tolerant as well as the nontolerant strains. Daptomycin was as effective alone as in combination with rifampin. In contrast, tolerance influenced the prophylactic effects of vancomycin and teicoplanin. The proportion of rats with sterile vegetations after prophylaxis with vancomycin or teicoplanin at a low dose was lower for those infected with the tolerant strain than for those infected with the nontolerant strain. A low dose of daptomycin was equally effective against the tolerant and the nontolerant strains. However, higher doses of all three antibiotics afforded almost full protection against both strains. PMID- 8203844 TI - Effect of a fat- and calcium-rich breakfast on pharmacokinetics of fleroxacin administered in single and multiple doses. AB - The effect of a fat- and liquid-calcium-rich meal on the pharmacokinetics of single and multiple doses of fleroxacin in 20 healthy men and women was investigated in a randomized crossover fashion. Fleroxacin was administered as 400 mg daily for 3 days and as a single 400 mg dose. Concurrent administration of fleroxacin with food resulted in a statistically significant (P < or = 0.05) decrease in the area under the curve (13.9% for multiple-dose administration, 10% for single-dose administration) and in the peak concentration (25.9% for multiple dose administration, 27% for single-dose administration) and a lengthening of the time to peak (more than doubled for single- and multiple-dose phases). In addition, by using an equivalence criteria of 80 to 125%, the two one-sided tests procedure indicated that the mean areas under the curves for fleroxacin administered in a fed and a fasted state were statistically bioequivalent (P < or = 0.05) for both the single- and multiple-dose regimens. Although a meal high in fat and containing liquid calcium reduces the peak concentration by approximately 25%, a minimal effect on bioavailability is seen with concomitant food administration. In addition, multiple-dose bioavailability studies appear to give similar information to single-dose studies while representing the clinical setting more closely. PMID- 8203845 TI - Pharmacokinetics of antiviral polyoxometalates in rats. AB - Polyoxometalates are soluble mineral compounds formed principally of oxide anions and early transition metal cations. The polyoxometalates K12H2[P2W12O48].24H2O (JM 1591), K10[P2W18Zn4(H2O)2O68].20H2O (JM 1596), and [(CH3)3NH]8[Si2W18Nb6O77] (JM 2820) demonstrate potent antiviral activity against human immunodeficiency virus types 1 and 2, herpes simplex virus, and cytomegalovirus in vitro. The preclinical pharmacokinetics of these three compounds were characterized after single-dose intravenous administration of 50 mg/kg to rats. Plasma, urine, and feces were collected for 168 h, and polyoxometalate concentrations were determined by atomic emission. Serum protein binding was measured by equilibrium dialysis. All three compounds were highly bound to serum proteins in a concentration-dependent manner. Total and unbound concentrations of the three compounds in plasma declined in a triexponential manner with terminal half-lives of 246.0 +/- 127.0, 438.4 +/- 129.4, and 32.2 +/- 5.37 h (mean +/- standard deviation) for JM 1591, JM 1596, and JM 2820, respectively. Systemic clearances based on total concentrations in plasma were low, averaging 0.016 +/- 0.002, 0.015 +/- 0.002, and 0.018 +/- 0.003 liter/h/kg for JM 1591, JM 1596, and JM 2820, respectively. The clearances of unbound compounds from plasma averaged 0.966 +/- 0.136, 0.050 +/- 0.005, and 0.901 +/- 0.165 liter/h/kg for JM 1591, JM 1596, and JM 2820, respectively. For JM 1596, the clearance of unbound compound from the kidneys was lower than the glomerular filtration rate (0.086 liter/h/kg), suggesting this polyoxometalate underwent renal tubular reabsorption. However, JM 1591 and JM 2820 appeared to undergo tubular secretion. The fraction of the dose recovered in urine was 11.5, 46.8, and 10.6% for JM 1591, JM 1596, and JM 2820, respectively. Approximately 5% of the dose of each polyoxometalate was recovered in feces. The steady-state volume of distribution based on total concentrations averaged 1.44 liters/kg for JM 1591, 2.39 liters/kg for JM 1596, and 0.59 liter/kg for JM 2820, indicating moderate to wide distribution throughout the body. All three compounds were detected in various tissues 1 week after single-dose administrations, with the highest levels found in the kidneys and liver. The results of this study indicate that the disposition of polyoxometalates is highly dependent on their molecular structure. PMID- 8203846 TI - Antimalarial effects of rifampin in Plasmodium vivax malaria. AB - The antimalarial effects of rifampin in 60 adults with Plasmodium vivax malaria were assessed. There were three treatment groups: rifampin (20 and 15 mg/kg of body weight per day for 1 and 4 days, respectively; n = 5); rifampin followed by primaquine (15 mg of base per day for 14 days; n = 25), and chloroquine (25 mg of base per kg over 3 days) followed by primaquine (n = 30). All patients were hospitalized till clearance of fever and parasites, and 45 patients stayed in the hospital for 1 month. Despite initial clearance of fever in all patients and a > or = 6-fold reduction in parasitemia per 48-h life cycle, rifampin alone was not effective: all five patients had subsequent R2-like parasitological responses. All patients treated with rifampin-primaquine cleared both fever and parasitemia, but the therapeutic responses were slower than those following treatment with chloroquine-primaquine. Final fever clearance times were significantly longer (mean [standard deviation] = 43 [35] versus 27 [19] h; P = 0.046), and the parasite clearance times (to 50 and 90% of admission parasite counts and to a level undetectable in a peripheral blood smear) were also significantly greater (P = 0.053 to < 0.001). However, reappearance of infection occurred in only one patient treated with rifampin-primaquine. The results of this study suggest that rifampin at the usual therapeutic doses has partial activity against blood stages of P. vivax in humans but that used alone it is insufficient for cure. Rifampin might therefore be of value in combination antimalarial therapy. PMID- 8203847 TI - Clinical trial of clarithromycin for lepromatous leprosy. AB - Clarithromycin was administered to nine previously untreated lepromatous leprosy patients. Patients received two 1,500-mg doses on the first day, followed by 7 days of no treatment, in order to evaluate the potential efficacy of intermittent therapy. Patients then received 1,000 mg daily for 2 weeks followed by 500 mg daily for 9 weeks. The efficacy of therapy was monitored clinically, by changes in morphological index, mouse footpad infectivity, and radiorespirometric activity of Mycobacterium leprae obtained from serial biopsies and by serum levels of phenolic glycolipid I. Clarithromycin was well tolerated, with only minor side effects noted in two patients. Most patients showed reductions in morphological index and radiorespirometry 1 week after the first two doses. Within 3 weeks of starting treatment (total of 17 g of clarithromycin), biopsy derived M. leprae specimens from all patients had a morphological index of zero, were noninfectious for mice, and had less than 1% of the radiorespirometric activity of pretreatment specimens. Reductions in serum phenolic glycolipid I levels were observed for most patients at 3 weeks. Significant clinical improvement was evident after 4 weeks of treatment. All analyses indicate that clarithromycin is rapidly bactericidal for M. leprae in humans. PMID- 8203848 TI - Dose-dependent antifungal activity and nephrotoxicity of amphotericin B colloidal dispersion in experimental pulmonary aspergillosis. AB - We investigated the safety and efficacy of amphotericin B colloidal dispersion (ABCD) for the treatment of invasive pulmonary aspergillosis in persistently granulocytopenic rabbits. Treatment groups included ABCD in dosages of 1, 5, and 10 mg/kg/day intravenously or conventional desoxycholate amphotericin B (DAmB) at 1 mg/kg/day intravenously. Antifungal activity was directly related to increasing dosage of ABCD as determined by the concentration of Aspergillus fumigatus organisms in lungs and the frequency of hemorrhagic pulmonary lesions. At 5 and 10 mg/kg/day, there was a significant reduction in the tissue burden of A. fumigatus as measured by percent culture-positive lobes and CFU per gram of tissue (P < or = 0.001), whereas at 1 mg/kg/day measured by percent culture positive lobes and CFU per gram of tissue (P < or = 0.001), whereas at 1 mg/kg/day the tissue burden of A. fumigatus was not significantly different from that in untreated controls. Microbiological clearance was significantly greater at 1 mg of DAmB per kg per day than at 1 mg of ABCD per kg per day (P < or = 0.001). There was no difference in microbiological clearance of bronchoalveolar lavage fluid among the treatment groups as measured by CFU per milliliter. As determined by survival, ABCD at 5.0 mg/kg/day was more effective than DAmB at 1.0 mg/kg/day and ABCD at 10 mg/kg/day. ABCD at 10 mg/kg/day was more nephrotoxic than the lower dosages of ABCD and resulted in higher mortality. Impairment of glomerular filtration developed as a direct function increasing the ABCD dosage (r = 0.77; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8203849 TI - Efficacies of liposome-encapsulated clarithromycin and ofloxacin against Mycobacterium avium-M. intracellulare complex in human macrophages. AB - The therapeutic efficacies of liposome-encapsulated ofloxacin and clarithromycin against Mycobacterium avium-M. intracellulare (MAI) were evaluated in a model of intramacrophage infection. Liposome encapsulation was found to markedly enhance the uptake of each of the drugs by human macrophages. The human blood-derived macrophages were infected at day 7 of culture with MAI. Treatment was initiated 24 h after the infection, and the number of intracellular bacteria was determined at days 2, 3, and 4. Liposome entrapment of either ofloxacin or clarithromycin significantly (P < 0.005) enhanced the activities of the drugs when compared with the antimycobacterial effects of equivalent concentrations of the free (unentrapped) drugs. The drugs were used at concentrations close to their clinically achievable peak levels. The efficacy of clarithromycin, either in the free or liposome-entrapped form, was markedly higher than that of ofloxacin. Liposome-encapsulated ofloxacin or clarithromycin plus ethambutol was, in each case, more effective in organism eradication (P < 0.005) than each agent used singly. These results suggest that liposome-encapsulated clarithromycin may be more effective than the free form of the drug against MAI infections in vivo, and the use of a combination therapy with ethambutol could further enhance the efficacy. PMID- 8203850 TI - Comparative in vitro exoenzyme-suppressing activities of azithromycin and other macrolide antibiotics against Pseudomonas aeruginosa. AB - The inhibitory effects of azithromycin (AZM), a new 15-membered macrolide antibiotic, on the production of exotoxin A, total protease, elastase, and phospholipase C by Pseudomonas aeruginosa were determined, and the virulence suppressing effects of AZM were compared with those of erythromycin (EM), roxithromycin (RXM), and rokitamycin (RKM). The effect of exposure of P. aeruginosa PA103 or B16 in cultures to sub-MICs of these macrolide antibiotics on the production of exoenzymes was determined. AZM suppressed the in vitro production of extracellular and intracellular exotoxin A by P. aeruginosa PA103 more than did EM, even at a concentration of only 2 micrograms/ml. At concentrations of between 4 and 32 micrograms/ml, AZM also inhibited total protease, elastase, and phospholipase C production by P. aeruginosa B16 more than did EM, RXM, and RKM. AZM was effective in suppressing exotoxin A and total protease production through 24 h of incubation in the presence of drug at sub MICs, but it had no significant effect on either the growth of P. aeruginosa or its total protein production. Moreover, at a concentration of 4 micrograms/ml, AZM suppressed exoenzyme production by other strains of P. aeruginosa more than did EM. These findings indicate that AZM, EM, RXM, and RKM each has an inhibitory effect on exoenzyme production separate from the antimicrobial effect and that, of these macrolides, AZM has the strongest virulence-suppressing effect. PMID- 8203851 TI - In vitro activities of two glycylcyclines against gram-positive bacteria. AB - The glycylcyclines designated CL 329,998 and CL 331,002 are N,N dimethylglycylamido derivatives of minocycline and 6-demethyl-6 deoxytetracycline, respectively. In vitro activities of these two antimicrobial agents were compared with those of tetracycline, minocycline, and seven other antimicrobial agents against 412 gram-positive organisms. Both new drugs were significantly more active than minocycline against methicillin-resistant Staphylococcus aureus (MICs for 90% of isolates tested, 0.25 and 0.5 microgram/ml versus 4 micrograms/ml). CL 329,998 inhibited all streptococci, lactobacilli, and Leuconostoc spp. at concentrations of < or = 0.5 microgram/ml, with CL 331,002 slightly less active against some species. All enterococci, including minocycline resistant and multidrug-resistant isolates, were inhibited at < or = 0.5- and < or = 1.0-microgram/ml concentrations of the new drugs, respectively. Only bacteriostatic activity was evident by time-kill curves. The two glycylcyclines demonstrated activities in vitro that were superior to those of minocycline against several gram-positive bacterial species, and at relatively low concentrations, they inhibited isolates resistant to both tetracycline and minocycline. PMID- 8203852 TI - Active efflux of chloramphenicol in susceptible Escherichia coli strains and in multiple-antibiotic-resistant (Mar) mutants. AB - The multiple-antibiotic resistance (mar) locus (min 34) regulates a resistance to chloramphenicol in Escherichia coli that does not involve acetyltransferase. Transport studies showed that wild-type cells had an apparent endogenous active efflux of chloramphenicol which depended on the proton motive force. This efflux was not altered by a 39-kb chromosomal deletion which included the mar locus. Nevertheless, mutations at the mar locus led to a stronger net chloramphenicol efflux. Therefore, a gene encoding the putative efflux system cannot be at the mar locus but may be positively influenced by that locus. PMID- 8203854 TI - Randomized comparison of aztreonam and chloramphenicol in treatment of typhoid fever. AB - Patients with clinical typhoid fever plus a blood, bone marrow, or bile positive for Salmonella typhi or Salmonella paratyphi were included in an open clinical trial to compare the efficacy of aztreonam (6 g/day [2 g intravenously every 8 h]) given for 10 days with that of chloramphenicol (50 mg/kg of body weight per day [intravenously or orally]) administered for 14 days. A total of 44 patients, 22 in each group, were included in the study, and both groups were comparable in terms of baseline parameters. All patients randomized to receive chloramphenicol completed the 14 days of treatment, while two patients randomized to receive aztreonam developed an intestinal hemorrhage, and a third patient elected to withdraw from the trial. Defervescence occurred more quickly in the subjects receiving chloramphenicol than in those receiving aztreonam (P < 0.05). All patients in the chloramphenicol group were clinically cured during therapy, while four patients (21%) in the group receiving aztreonam were declared clinical treatment failures. None of the 19 patients receiving aztreonam, compared with 7 of 22 (32%) patients receiving chloramphenicol, had a positive blood culture after 24 h of therapy (P < 0.05). Adverse experiences were unusual and mild. In the study, aztreonam was less effective than chloramphenicol with regard to clinical effectiveness and time of defervescence but was more effective in the elimination of the infecting Salmonella organisms from the bloodstream. PMID- 8203853 TI - Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem cilastatin. The Severe Pneumonia Study Group. AB - Intravenously administered ciprofloxacin was compared with imipenem for the treatment of severe pneumonia. In this prospective, randomized, double-blind, multicenter trial, which included an intent-to-treat analysis, a total of 405 patients with severe pneumonia were enrolled. The mean APACHE II score was 17.6, 79% of the patients required mechanical ventilation, and 78% had nosocomial pneumonia. A subgroup of 205 patients (98 ciprofloxacin-treated patients and 107 imipenem-treated patients) were evaluable for the major efficacy endpoints. Patients were randomized to receive intravenous treatment with either ciprofloxacin (400 mg every 8 h) or imipenem (1,000 mg every 8 h), and doses were adjusted for renal function. The primary and secondary efficacy endpoints were bacteriological and clinical responses at 3 to 7 days after completion of therapy. Ciprofloxacin-treated patients had a higher bacteriological eradication rate than did imipenem-treated patients (69 versus 59%; 95% confidence interval of -0.6%, 26.2%; P = 0.069) and also a significantly higher clinical response rate (69 versus 56%; 95% confidence interval of 3.5%, 28.5%; P = 0.021). The greatest difference between ciprofloxacin and imipenem was in eradication of members of the family Enterobacteriaceae (93 versus 65%; P = 0.009). Stepwise logistic regression analysis demonstrated the following factors to be associated with bacteriological eradication: absence of Pseudomonas aeruginosa (P < 0.01), higher weight (P < 0.01), a low APACHE II score (P = 0.03), and treatment with ciprofloxacin (P = 0.04). When P. aeruginosa was recovered from initial respiratory tract cultures, failure to achieve bacteriological eradication and development of resistance during therapy were common in both treatment groups (67 and 33% for ciprofloxacin and 59 and 53% for imipenem, respectively). Seizures were observed more frequently with imipenem than with ciprofloxacin (6 versus 1%; P = 0.028). These results demonstrate that in patients with severe pneumonia, monotherapy with ciprofloxacin is at least equivalent to monotherapy with imipenem in terms of bacteriological eradication and clinical response. For both treatment groups, the presence of P. aeruginosa had a negative impact on treatment success. Seizures were more common with imipenem than with ciprofloxacin. Monotherapy for severe pneumonia is a safe and effective initial strategy but may need to be modified if P. aeruginosa is suspected or recovered from patients. PMID- 8203855 TI - Combination chemotherapy of drug-resistant Trypanosoma brucei rhodesiense infections in mice using DL-alpha-difluoromethylornithine and standard trypanocides. AB - Combinations of DL-alpha-difluoromethylornithine (DFMO; eflornithine; Ornidyl) with either suramin or melarsen oxide were found to be effective against acute laboratory model infections with Trypanosoma brucei rhodesiense. We used clinical isolates known to be resistant to these drugs when used singly. An infection with a melarsen oxide-refractory isolate was cured by a combination of low-dose DFMO (0.5% in the drinking water) plus low-dose suramin (1 mg/kg of body weight given intraperitoneally). Another strain, moderately resistant to arsenical drugs, was cured with combinations of 4% DFMO with 5 mg of melarsen oxide per kg. Furthermore, a combination of DFMO (2% in the drinking water) and suramin (20 mg/kg) provided a 100% cure rate in a central nervous system model, although the same doses of these drugs used singly were completely ineffective. The synergism of DFMO and suramin against an acute infection was improved when suramin was given at the end of the DFMO administration. No adverse interactions were observed when high doses of DFMO combined with high doses of suramin were administered to uninfected mice. These results suggest that combinations of DFMO and suramin should be examined clinically for activity in arsenical-drug refractory cases of East African sleeping sickness. PMID- 8203856 TI - Rifabutin is active in murine models of toxoplasmosis. AB - Rifabutin, a semisynthetic derivative of rifamycin S, was examined alone and in combination with other drugs for activity in treatment of systemic toxoplasmosis and toxoplasmic encephalitis in murine models. One hundred percent of the mice infected with a lethal inoculum of tachyzoites or cysts of Toxoplasma gondii were protected against death by treatment with doses of 400 or 300 mg of rifabutin per kg administered alone for 10 days. Doses of 200 mg/kg protected at least 80% of the mice, and doses of 100 mg/kg protected 10 to 40% of the infected mice against death. Doses of 50 mg/kg were not protective but caused a delay in time to death. Combination of nonprotective (50-mg/kg) or slightly protective (100-mg/kg) doses of rifabutin with doses of sulfadiazine, pyrimethamine, clindamycin, or atovaquone that did not confer any protection against death from toxoplasmosis when administered alone resulted in remarkable enhancement of the in vivo activities of all of these drugs. Seventy-five percent of the infected mice survived when treated with 100 mg of rifabutin per kg per day combined with the ineffective dose of 10 mg of pyrimethamine per kg. A dose of 50 mg of rifabutin per kg in combination with the ineffective dosages of clindamycin (25 mg/kg/day), atovoquone (5 mg/kg/day), and sulfadiazine (80 mg per liter of drinking water) protected at least 80, 60, and 60% of the mice against death, respectively. The inflammatory responses in the brains of mice treated for 30 days with 200 mg of rifabutin per kg per day were significantly reduced compared with those in the brains of untreated controls. These observations suggest that clinical trials with rifabutin for treatment and prevention of human toxoplasmosis may be justified, particularly when the drug is used in combination with other drugs with activity against T. gondii. PMID- 8203857 TI - Randomized trial of the addition of gram-positive prophylaxis to standard antimicrobial prophylaxis for patients undergoing autologous bone marrow transplantation. AB - The purpose of the study reported here was to investigate the impact of prophylaxis against gram-positive infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplantation in a randomized trial. Forty-three patients undergoing high-dose chemotherapy with autologous bone marrow transplant were enrolled in a nonblinded randomized trial to receive or not to receive prophylaxis for gram-positive infections with 10(6) U of penicillin intravenously (i.v.) every 6 h (q6h) (if penicillin allergic, 750 mg of vancomycin i.v. q12h) in addition to standard antimicrobial prophylaxis with 400 mg of norfloxacin orally three times a day, 200 mg of fluconazole orally once a day, and 5 mg of acyclovir per kg of body weight i.v. q12h. The patients were being treated for germ cell cancer (n = 15), breast cancer (n = 16), Hodgkin's disease (n = 3), non-Hodgkin's lymphoma (n = 4), acute myeloid leukemia (n = 1), acute lymphoblastic leukemia (n = 1), and ovarian cancer (n = 3). The trial was stopped because of excess morbidity in the form of streptococcal septic shock in the group not receiving gram-positive prophylaxis. There were significantly fewer overall infections (10 versus 3; P = 0.016) and streptococcal infections (9 versus 1; P = 0.0078) in the group receiving gram-positive prophylaxis. There were no significant differences in the numbers of deaths, duration of broad spectrum antibiotics, or incidence of neutropenic fever between the two groups. Prophylaxis for gram-positive infections with penicillin or vancomycin is effective in reducing the incidence of streptococcal infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplant. However, this approach may carry a risk of fostering resistance among streptococci to penicillin or vancomycin. PMID- 8203858 TI - Therapeutic efficacy of monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan alone and in combination with amphotericin B. AB - The therapeutic efficacy of the immunoglobulin G1 (IgG1) monoclonal antibody (MAb) 2H1 to the Cryptococcus neoformans capsular polysaccharide was studied with and without amphotericin B (AmB) in a murine model of intravenous (i.v.) infection. MAb and AmB were administered by intraperitoneal (i.p.) injection after i.v. infection with a C. neoformans serotype D strain. Intraperitoneal administration of MAb 2H1 resulted in rapid distribution to the intravascular compartment, and the half-lives of i.p. and i.v. administered MAb were similar. Administration of MAb 2H1 alone resulted in increased survival, decreased lung fungal burden, and reduced serum glucuronoxylomannan antigen levels when given 2 to 6 h but not 24 h after infection. In vivo, the combination of MAb 2H1 and AmB was more effective at prolonging survival than either agent alone. MAbs of IgM, IgG1, IgG3, and IgA isotypes given 1 day after infection were effective in reducing serum GXM-D levels, with their relative efficacy being IgG1 > IgG3 > IgM > IgA. In vitro, MAb 2H1 was a potent opsonin of C. neoformans and the combination of MAb 2H1 and AmB was more effective than either agent alone in decreasing C. neoformans colony counts in the presence of the murine macrophage cell line J774.16. The results confirm that capsule-binding MAbs can enhance the effect of AmB against C. neoformans and provide support for considering combined therapy in humans. PMID- 8203859 TI - Tuftsin-bearing liposomes as rifampin vehicles in treatment of tuberculosis in mice. AB - The antitubercular activity of rifampin was considerably increased when it was encapsulated in egg phosphatidylcholine liposomes. A further increase in the activity was observed when the macrophage activator tetrapeptide tuftsin was grafted on the surface of the drug-loaded liposomes. Intermittent treatments (twice weekly) with these preparations were significantly more effective than the continuous treatments. Rifampin delivered twice weekly for 2 weeks in tuftsin bearing liposomes was at least 2,000 times more effective than the free drug in lowering the load of lung bacilli in infected animals. However, pretreatment with drug-free tuftsin-bearing liposomes did not render the pretreated animals resistant to the Mycobacterium tuberculosis infections, neither did it appreciably increase the chemotherapeutic efficacy of the liposomized rifampin. These results clearly demonstrate that liposome targeting to macrophages could considerably increase the antitubercular activity of liposomized drugs such as rifampin. Also, it shows that immunoprophylactic treatment with macrophage activators such as tuftsin does not afford any advantage in treatment of tuberculosis infections, presumably because of inactivation of the primed macrophages by the mycobacterial sulfatides. PMID- 8203860 TI - In vitro antibacterial activity of AM-1155, a novel 6-fluoro-8-methoxy quinolone. AB - The in vitro antibacterial activity of AM-1155 against a wide variety of clinical isolates was compared with those of other fluoroquinolones. The MICs of AM-1155 for 90% of Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis isolates tested were 0.10, 0.39, and 0.78 microgram/ml, respectively. The antibacterial activity of AM-1155 against gram-positive bacteria and anaerobes was comparable to those of sparfloxacin and tosufloxacin. AM-1155 inhibited 90% of most species of the family Enterobacteriaceae at a concentration of 0.39 microgram/ml. AM-1155 generally had activity comparable to that of sparfloxacin against gram-negative bacteria. AM-1155 showed moderate activity against methicillin- and quinolone-resistant S. aureus. AM-1155 demonstrated bactericidal activity at the MIC. The frequency of occurrence of spontaneous mutants resistant to four times the MIC of AM-1155 was < 1 x 10(9) for S. aureus, Escherichia coli, and Pseudomonas aeruginosa. AM-1155 strongly inhibited the supercoiling activities of DNA gyrases purified from E. coli and S. aureus. PMID- 8203861 TI - Effects of broad-spectrum antibiotics on colonization of gastrointestinal tracts of mice by Candida albicans. AB - Three-month-old, male, Crl:CD1 (ICR) BR mice were fed chow containing Candida albicans or regular chow. Subsequently, both groups were given either antibiotics or normal saline for 10 days. Stool cultures were performed immediately before administration, at the end of antibiotic administration, and 1 week after the discontinuation of antibiotics, to determine the effect on the concentration of C. albicans in the stools. The stools of mice fed C. albicans and given antibiotics had substantially higher Candida counts than those of control mice fed C. albicans and given saline. Significantly higher candidal concentrations were observed in the stools of mice given chloramphenicol compared with those of mice given ciprofloxacin, sulfamethoxazole-trimethoprim, and ampicillin. No mice developed histopathological evidence of local gastrointestinal invasion or disseminated candidiasis. In this mouse model, Candida colonization increases substantially after the administration of antimicrobial agents with broad spectra and anaerobic activities. PMID- 8203862 TI - Development of experimental respiratory infections in neutropenic rats with either penicillin-resistant Streptococcus pneumoniae or beta-lactamase-producing Haemophilus influenzae. AB - Acute respiratory infections with penicillin-resistant strains of Streptococcus pneumoniae and a beta-lactamase-producing strain of Haemophilus influenzae were established in neutropenic weanling rats. By use of nonsurgical intrabronchial instillation of the bacteria suspended in molten agar, reproducible, acute respiratory infections suitable for experimental antibiotic efficacy studies were established. PMID- 8203863 TI - Comparative in vitro activity of DU-6859a, a new fluoroquinolone agent, against gram-positive cocci. AB - The in vitro activity of DU-6859a (DU), a new fluoroquinolone agent, was evaluated against 233 gram-positive cocci and was compared with those of ciprofloxacin, vancomycin, nafcillin, and ampicillin. The MICs of DU for 90% of the staphylococci tested were < or = 0.06 microgram/ml. All of the groups A and B and viridans group streptococci were inhibited by < or = 0.125 microgram of DU per ml, which was 32-fold more active than ciprofloxacin. On the basis of MICs for 90% of the strains tested, DU was 32- and 16-fold more active than ciprofloxacin against Enterococcus faecalis and Enterococcus faecium, respectively. The bactericidal activity of DU was demonstrated by time-kill techniques against all ciprofloxacin-susceptible enterococci. DU shows promise for the treatment of infections with gram-positive cocci and warrants further evaluation by in vitro and in vivo studies. PMID- 8203864 TI - Fever and associated changes in glomerular filtration rate erase anticipated diurnal variations in aminoglycoside pharmacokinetics. AB - Netilmicin (4.5 mg/kg of lean body weight) was administered intravenously once every 24 h at 10 a.m. to 23 patients (group I) and at 10 p.m. to 20 patients (group II) with severe infection. No significant differences (P > 0.05) in peak and trough concentrations in serum were found between groups I and II (peak, 12.9 +/- 3.7 versus 12.8 +/- 4.4 mg/liter, respectively; trough, 0.7 +/- 0.6 versus 0.8 +/- 0.6 mg/liter, respectively [mean +/- standard deviation]). Pharmacokinetic parameters (half-life [5.0 +/- 2.2 versus 4.9 +/- 1.8 h], volume of distribution [0.32 +/- 0.04 versus 0.35 +/- 0.06 liter/kg], and total clearance [0.920 +/- 0.417 versus 1.015 +/- 0.546 ml/min/kg]) were similar in the two groups and not influenced by the time of administration. These data suggest that, in the once-daily schedule, 10 a.m. or 10 p.m. administration had no influence on netilmicin levels in serum and pharmacokinetic parameters in these ill febrile patients. PMID- 8203865 TI - A changing pattern of susceptibility of Xanthomonas maltophilia to antimicrobial agents: implications for therapy. AB - The in vitro susceptibilities of 130 Xanthomonas maltophilia isolates to 12 antibiotics--trimethoprim-sulfamethoxazole, minocycline, ticarcillin-clavulanate, ceftazidime, cefoperazone, cefoperazone-sulbactam, imipenem, ciprofloxacin, and the investigational quinolones PD 117558, PD 117596, PD 127391, and sparfloxacin- were determined by a microtiter broth dilution technique. Other than the investigational quinolones, the most active antibiotics were minocycline, trimethoprim-sulfamethoxazole, and ticarcillin-clavulanate, in order. However, the first two were not bactericidal, while about half of the isolates exhibited intermediate susceptibility to ticarcillin-clavulanate. Patterns of susceptibility to trimethoprim-sulfamethoxazole and ciprofloxacin relative to the years of isolation of these strains reflected the development of resistance to the antibiotic prophylaxis practices in the hospital. We recommend that a combination of antibiotics, such as trimethoprim-sulfamethoxazole, minocycline, and ticarcillin-clavulanate, at or close to the maximum tolerated doses be in the treatment of serious X. maltophilia infections. PMID- 8203866 TI - Impact of dosing schedule upon suppression of a retrovirus in a murine model of AIDS encephalopathy. AB - We studied the impact of zidovudine (AZT) in Cas-Br-M murine leukemia virus infected NFS-N mice after administration by once-daily bolus or continuous infusion. While higher peak concentrations of AZT were achieved by once-daily dosing, continuous AZT infusion at 25 micrograms/h maintained levels > 1 microM in plasma and > 0.2 microM in the brain. Continuous infusion provided significantly better viral inhibition, even though total doses were only one third that of the once-daily therapy group. PMID- 8203867 TI - Determination of pefloxacin concentration in mesenteric lymph nodes by high performance chromatography. AB - Ten patients who had undergone laparotomies for different abdominal pathological conditions were studied to determine the levels of pefloxacin in mesenteric lymph nodes. Each patient was given 400 mg of oral pefloxacin every 12 h for the 3 days prior to surgery. Drug levels in tissue were determined by high-pressure liquid chromatography (reverse phase); the mean +/- standard deviation was 17.1 +/- 11.9 micrograms/g, with a range of 2.12 to 36.6 micrograms/g. This indicates an adequate pefloxacin concentration in lymph nodes and makes the drug a good option for the treatment of conditions in which lymph nodes act as an infection promoting and/or relapse-favoring factor. PMID- 8203868 TI - Preparation and preliminary characterization of poly(ethylene glycol)-pepstatin conjugate. AB - The carboxyl function of pepstatin has been coupled, through an amide bond, to methoxypoly(ethylene glycol) (5 kDa), to which an amino function had been previously grafted. The mPEG-pepstatin conjugate inhibits hog pepsin (aspartic proteinase) in vitro as pepstatin itself, however, with a 400 times higher apparent Ki. The conjugate apparently does not inhibit proteinases belonging to other proteinase families such as serine (trypsin, carboxypeptidase Y), cysteine (Papaya proteinase III), or metallo (collagenase) proteinases. PMID- 8203869 TI - Oxidation of dibenzothiophene catalyzed by heme-containing enzymes encapsulated in sol-gel glass. A new form of biocatalysts. AB - We have encapsulated several hemoproteins in the sol-gel glass to catalyze the oxidation reaction of dibenzothiophene (model for organic sulfur compounds in coal) with hydrogen peroxide. In addition to cytochrome c and myoglobin, which have previously been encapsulated in sol-gel glasses, two other hemoproteins, horseradish peroxidase and bovine blood hemoglobin, have now been successfully immobilized in sol-gel media with the retention of their spectroscopic properties. All four hemoproteins studied also demonstrate similar catalytic activities toward the oxidation of dibenzothiophene as compared with the results obtained with the proteins in solution. In the case of encapsulated cytochrome c, the more water-soluble S-oxide was obtained with much higher selectivity over the less water-soluble sulfone (S-oxide/sulfone = 7.1) as compared to what was obtained in the aqueous/organic medium (S-oxide/sulfone = 2.3). Because of the advantage of easy separation of the encapsulated proteins from the liquid reaction mixture, it is clear from these studies that the immobilization of active hemoproteins in the solid glass media could serve as more practical biocatalysts. PMID- 8203870 TI - Mechanism of DNA-drug interactions. AB - Over the last two decades many strategies have been planned to design specific drugs for rare diseases to target their action at the DNA level. Advancements in our understanding of the interactions of small nonpeptide molecules with DNA have opened the doors for "rational" drug design. Special methods have now been developed to give accurate account of the precise location of ligand-DNA adducts on target DNA. We are now in a position to think of designing ligands that recognize particular sequences of base pairs. This work will allow us to enter into a new era of gene therapy for diseases like Cystic fibrosis, Alzheimer's disease and many related disorders at genetic level. These ligands can also be employed in the treatment of various types of cancers. They may also be useful as highly specific probes to locate particular sequences in the genomic DNA. PMID- 8203871 TI - Purification and properties of uricase from Candida sp. and its application in uric acid analysis in serum. AB - The purification of uricase from Candida sp. was carried out by precipitation with ammonium sulfate then further proceeded with Sephadex G200, and DEAE cellulose DE52 chromatographies. The specific activity of the enzyme was enhanced from 0.05-12 (U/mg protein). The purity of the enzyme was judged to be homogeneous by SDS-PAGE. Some of the general properties of enzyme were investigated. The optimum reaction pH and temperature were 8.5 and 30 degrees C, respectively. The enzyme was stable at a pH range from 8.5-9.5 and at temperatures lower than 35 degrees C. The apparent Km value of the enzyme was calculated to be about 5.26 x 10(-6) mol/L. The molecular weight was determined to be 70,000-76,000 by the gel filtration and SDS-PAGE techniques. The isoelectric point was determined to be pH 5.6. The effects of some metallic ions on enzyme activity and stability were discussed. The partial purified uricase was used in serum uric acid determination. The within-batch imprecision percentage ranged from 2.16-2.63 and the between-batch imprecision percentage ranged from 2.4-3.6. The recovery ratio were from 96-101%. The correlation among this method and Boehringer, Roche, or Biotrol enzymatic kits were Y = 1.086x-0.50 (r = 0.981), Ya = 0.959x-0.29 (r = 0.97), and Yb = 1.110x-0.45 (r = 0.956), respectively. A linear calibration curve was obtained at 2.5-15 mg/dL uric acid. The stability of reagents and the effects of some substances in serum were also surveyed. PMID- 8203872 TI - L-malic acid production by entrapped Saccharomyces cerevisiae into polyacrylamide gel beads. AB - The yeast Saccharomyces cerevisiae was entrapped within polyacrylamide gel beads by employing a procedure that uses sodium dodecylsulfate as a detergent to improve the spherical configuration of the beads. The resulting preparation showed a rate of fumarate bio-conversion to L-malic acid about 60 times higher than that found for the free cells. Almost all fumarate was converted in 30 min of incubation. The thermal stability of the immobilized cells did not significantly differ from the free cells. An optimal pH of 5.7 was found for the immobilized preparation and no succinic acid was detected as a byproduct in the incubation mixture. PMID- 8203873 TI - Kinetics of biomethanation of solid tannery waste and the concept of interactive metabolic control. AB - Anaerobic digestion of calf skin collagenous waste was optimized for a batch process based on accelerated maximal methane yield per gram of input volatile solid. A kinetic analysis with respect to changes in the levels of volatile solid, collagen, amino sugars, amino acids, hydroxyproline, ammonium ions, and volatile fatty acid were followed for a period of 80 d. Distinct metabolic phases included an initial high rate collagenolysis for 4d, with 50% degradation and was followed by an acidogenic phase between 4-12 d with volatile fatty acids levels increasing to 215 mmol/L. Subsequently methanogenesis ensued and was maximal between 12-24 d when volatile fatty acids attained steady state levels. During the period of 80 d, the overall decrease in volatile solid level was 65%, whereas the collagen level declined by 85% with 0.45 L of methane yield/g of volatile solid degraded. Based on the levels of various metabolites detected, the concept of interactive metabolic control earlier proposed has been validated. PMID- 8203874 TI - Postcardiac catheterization time-in-bed study: enhancing patient comfort through nursing research. AB - Cardiac catheterization has become a routine diagnostic procedure. Little has been written about standards for nursing care related to bed rest postcatheterization. The purpose of this experimental study was to determine whether there was a significant difference in incidence of bleeding from catheter insertion site between those patients who remained in bed for 12 hours and those who remained in bed for 6 hours post-procedure. There was no significant difference between the two groups. Postprocedure bed rest was reduced from 12 to 6 hours in this tertiary care medical center. Decreasing time in bed reduced cost and patient discomfort. PMID- 8203875 TI - Prodromal falls among older nursing home residents. AB - Although numerous studies have identified medical antecedents of falls among the elderly (premonitory), few have examined falls as a possible predictor of subsequent disease onset (prodromal falling). This study compared disease incidence (up to 12 months after the first fall) among fallers (n = 42) and nonfallers (n = 20) selected from 236 admissions to the health care center of a nursing home. Data collected on up to five new falls per resident (total of 102 falls) included (a) predictors of falls, (b) circumstance of falls, and (c) postfall events. Results showed that although faller and nonfaller groups were similar on admission in both numbers and types of medical diseases, fallers showed greater frequency of developing new medical problems in the 12-month postfall follow-up period. However, no particular medical diseases were found to singularly account for the greater number of medical problems evident among fallers. Additionally, fallers tended to be more impaired on admission in ambulation and daily living abilities than nonfallers. PMID- 8203876 TI - Measures of salivary secretory immunoglobulin A and state anxiety after a nursing back rub. AB - This study examined the effects of a 10-minute nursing back rub on salivary secretory immunoglobulin A (s-IgA) and state anxiety in well older adult subjects. A control group (n = 14) received no intervention, and an experimental group (n = 18) received a slow stroke effleurage back rub. All subjects initially completed the state portion of the Spielberger State/Trait Anxiety Inventory (STAI) and provided a timed, nonstimulated saliva sample. Control subjects lay positioned in bed for 10 minutes, and experimental subjects received the back rub. Both groups then provided a second saliva sample and completed the STAI again. Anxiety scores decreased for both groups, but not significantly, and s-IgA concentration increased in the experimental group. This study provides rationale for further research into the holistic benefits of the nursing back rub and should encourage nurses to continue to provide caring touch interventions to patients. PMID- 8203877 TI - Nutrition locus of control and dietary behaviors of pregnant women. PMID- 8203878 TI - Issues in intervention research: maintaining integrity. PMID- 8203879 TI - Research grant implementation: staff development as a tool to accomplish research activities. PMID- 8203880 TI - The utility of the research problem statement. PMID- 8203881 TI - Thioprenols as hydrazinolysis products of prenylated proteins: dependence upon methylation of the prenylcysteine. AB - When prenylated proteins are treated with hydrazine at elevated temperatures, a substantial fraction of the prenylcysteines are cleaved at the C-S bond of the beta-carbon of cysteine. Thioprenols, the initial products of this reaction, are then reduced, over time, to hydrocarbons. This elimination reaction is favored several fold if the prenylcysteine is present as a carboxylate derivative rather than as a carboxyl terminal free amino acid. Thus, the pattern of elimination has the potential for detecting substitution (methylation) of prenylcysteines. In addition, the formation of thioprenols leads to more sensitive ways for determination of the prenylcysteines. PMID- 8203882 TI - Cartilage chondrolysis by fibronectin fragments is associated with release of several proteinases: stromelysin plays a major role in chondrolysis. AB - We have reported that three different Fn fragments (Fn-f) added to bovine articular cartilage cultured in serum-free DMEM cause marked elevation of proteoglycan (PG) degradation and release into the culture media. We report here that the PG release required the continual presence of Fn-f, that PG release still occurred when serum-free cultures were switched to bovine synovial fluid media, and that addition of recombinant IGF-1, TGF-beta, and recombinant interferon gamma to cultures did not affect Fn-f-mediated PG release. The Fn-f caused a 25-fold enhanced release of stromelysin-1 protein from cartilage by Day 1 and up to 120-fold by Day 3. The stromelysin form released was 43 kDa, the activated form of pro-stromelysin-1. This stromelysin form apparently played a major role in Fn-f-mediated PG release, since addition of Sepharose-bound anti stromelysin-1 to cartilage cultures greatly slowed rates of PG release. Potential activators of pro-stromelysin-1, plasmin, and u-PA (urinary plasminogen activator), were also detected in conditioned media of Fn-f-treated cartilage. u PA levels were increased in the presence of the Fn-f but by only a few fold. Addition of alpha-1-antiproteinase inhibitor, which can block enzymatic activity of u-PA, was found to inhibit about half the PG-releasing activity of the Fn-f. Levels of TIMP-1, the 30-kDa tissue inhibitor of metalloproteinases, which can inhibit stromelysin, doubled within 24 h when a Fn-f was added to culture. These data suggest that stromelysin-1 may be a major mediator of Fn-f-mediated PG release from cartilage. PMID- 8203883 TI - High concentrations of fibronectin fragments cause short-term catabolic effects in cartilage tissue while lower concentrations cause continuous anabolic effects. AB - We reported earlier that Fn fragments (Fn-f) added to bovine articular cartilage cultured in serum-free DMEM cause marked elevated release of protease activity within a few days. This results in greatly elevated rates of release of proteoglycan (PG). We have now extended our studies to 4-week cultures of cartilage in the presence of 10% serum. We report here that cartilage cultured with 0.01, 0.1, and 1 microM of an amino terminal 29-kDa Fn-f in 10% serum accelerated the loss of PG from the tissue during the first few days in a concentration-dependent manner. However, beyond this period PG content decreased much more slowly. During this early period, the 29-kDa Fn-f decreased rates of protein and PG synthesis up to 50% in a concentration-dependent fashion. Beyond this period, the synthesis rates began to increase in a mode inversely related to 29-kDa Fn-f concentration, up to 135% of Fn-f free control values. However, during the entire culture period, cartilage cultured with 1 nM 29-kDa Fn-f had higher PG contents and had enhanced rates of protein and PG synthesis. Since 1 nM 29-kDa Fn-f stabilized cartilage against decreases in PG content, we tested its ability to block the activity of higher 29-kDa Fn-f concentrations. Cartilage was preincubated for 7 days with 1 nM 29-kDa Fn-f, and then the culture adjusted to 100 nM 29-kDa Fn-f to cause PG depletion. The preincubated cartilage showed markedly enhanced resistance to PG depletion. Since the protective effect was similar to known properties of IGF-1, the ability of 20 ng/ml IGF-1 to block against the effects of 100 nM Fn-f was tested and shown to be similar in magnitude to that of 1 nM 29-kDa Fn-f. We propose that the initial catabolic effects of higher concentrations of Fn-f, followed by the later anabolic effects, may aid in tissue repair. Also, the continuous anabolic effects of lower concentrations may be involved in tissue homeostasis. PMID- 8203884 TI - Magnesium ion modulates the sensitivity of the mitochondrial permeability transition pore to cyclosporin A and ADP. AB - Regulation of the mitochondrial permeability transition pore has been investigated following the release of matrix solutes which normally participate in pore regulation. Under these conditions, neither cyclosporin A nor ADP induces pore closure, as judged by restoration of delta psi, unless Mg2+ is also added. Mg2+ alone is ineffective. In liver mitochondria, the Mg2+ effect is expressed over a 0 to 0.5 mM concentration range with higher concentrations inhibiting repolarization. In heart mitochondria, the inhibitory action of high Mg2+ is not seen and it can be shown that the Mg2+ effect on repolarization increases progressively up to a concentration of 5 mM. In liver mitochondria, when the pore is closed by maximally effective concentrations of Mg2+ plus cyclosporin A or Mg2+ plus ADP, reopening occurs upon the addition of carboxyatractyloside. The latter compound, however, fails to reopen the pore when Mg2+, cyclosporin A, and ADP are present simultaneously. In heart mitochondria, where higher Mg2+ concentrations can be employed, Mg2+ plus cyclosporin A or Mg2+ plus ADP produces pore closure in a carboxyatractyloside insensitive manner. Titration experiments support the adenine nucleotide translocase as the site at which carboxyatractyloside acts to regulate the pore. However, the action of ADP appears to involve a translocase-independent site. In intact mitochondria the action of carboxyatractyloside on pore opening is counteracted by oligomycin, apparently through inhibition of the F1F0 ATP synthase, with a consequent increase in the matrix space ADP/ATP ratio. It is concluded that the permeability transition pore induced by Ca2+ plus P(i) is not formed from the adenine nucleotide translocase although the translocase conformation is one of several factors which regulate the pore. The matrix Mg2+ concentration is also one of these factors. Formation of the pore by a Ca2+ and ADP binding protein is one model which is consistent with the present data. PMID- 8203885 TI - Synthesis of trilaurin by developing pisa seeds (Actinodaphne hookeri). AB - The developing seeds of Actinodaphne hookeri were investigated to delineate their ability to synthesize large amounts of trilaurin. Until 88 days after flowering the embryos contained 71% neutral lipids (NL) and 29% phospholipids (PL) and both these components contained C16:0, C18:0, C18:2, and C18:3 as the major fatty acids (FA). At 102 days after flowering the seeds began to accumulate triacylglycerols (TAG) and to synthesize lauric acid (C12:0). By 165 days after flowering, when the seeds were mature, they contained about 99% NL and 1% PL. At this stage the TAG contained exclusively C12:0, while the PL consisted of long chain fatty acids (LCFA) only. Leaf lipids in contrast did not contain any C12:0. Experiments on [1-14C]acetate incorporation into developing seed slices showed that at 88 days after flowering only 4% of the label was in TAG, 1% in diacylglycerols (DAG), and 87% in PL. One hundred two days after flowering seeds incorporated only 2% of the label into TAG, 30% into DAG, and 64% into PL. In contrast at 114 days after flowering 71% of the label was incorporated into TAG, 25% into DAG, and only 2% into PL. Analysis of labeled FA revealed that up to 102 days after flowering it was incorporated only into LCFA, whereas at 114 days after flowering it was incorporated exclusively into C12:0. Furthermore, 67% of the label in PL at 114 days after flowering was found to be dilaurylglycerophosphate. Analysis of the label in DAG at this stage showed that it was essentially in dilaurin species. These observations indicate the induction of enzymes of Kennedy pathway for the specific synthesis of trilaurin at about 114 days after flowering. Homogenates of seeds (114 days after flowering) incubated with labeled FA in the presence of glycerol-3-phosphate and coenzymes A and ATP incorporated 84% of C12:0 and 61% of C14:0, but not C16:0, C18:2, and C18:3, into TAG. In contrast the LCFA were incorporated preferentially into PL. It is concluded that, between 102 and 114 days after flowering, a switch occurs in A. hookeri for the synthesis of C12:0 and trilaurin which is tissue specific. Since the seed synthesizes exclusively C12:0 at 114 days after flowering onwards and incorporates specifically into TAG, this system appears to be ideal for identifying the enzymes responsible for medium-chain fatty acid as well as trilaurin synthesis and for exploiting them for genetic engineering. PMID- 8203886 TI - Several closely related glutathione S-transferase isozymes catalyzing conjugation of 4-hydroxynonenal are differentially expressed in human tissues. AB - A human acidic glutathione S-transferase, hGST 5.8, was isolated from heart, pancreas, and brain by a procedure involving immunoadsorption chromatography on immobilized antibodies raised against mouse mGSTA4-4. The human hGST 5.8 enzymes isolated from these tissues had similar pI (5.8) and subunit M(r) (24.5 kDa) values, showed about 17- to 20-fold higher specific activities for 4-hydroxynon-2 enal than that for 1-chloro-2,4-dinitrobenzene, and expressed glutathione peroxidase activity toward phospholipid hydroperoxides. In this respect, the enzymes belong together with rat GST 8-8 and mouse mGSTA4-4 to a subgroup of GSTs involved in the detoxification of lipid peroxidation products. Partial sequencing of CNBr-peptide fragments of hGST 5.8 proteins isolated from various human tissues revealed significant similarity to mGSTA4-4 and the existence of several distinct isoforms differing in their primary structures. These isoforms had similar but nevertheless clearly distinguishable catalytic properties. These results indicate the existence of multiple hGST 5.8-related genes in the humans, which is consistent with our previous studies showing the presence of several closely related genes for the mouse ortholog mGSTA4-4 (Zimniak et al., J. Biol. Chem., 1994, 269, 992-1000). PMID- 8203887 TI - Effects of denaturant and pressure on the intrinsic fluorescence of titin. AB - The intrinsic fluorescence of titin was analyzed in this present study. The average fluorescence wavelength of titin was 17 nm shorter than that of tryptophan in water, indicating that tryptophans in titin are not completely exposed to solvent. Guanidine hydrochloride (GdmCl) induced a red spectral shift of 17 nm, a decrease of total intensity of 33%, an increase of spectral bandwidth, and a decrease of anisotropy of 59%. The GdmCl concentration dependence of these fluorescence parameters indicated a two-state transition phenomenon with a transition midpoint at 2.6 M. The free energy change associated with this transition is in the range of 3-3.5 kcal/mol/domain, assuming that titin domains are unfolded independently. The anisotropy value also decreased 69% upon application of hydrostatic pressure up to 2.4 kbar, similar to the situation of GdmCl denaturation. However, the spectral red shift was 3.7-nm at a pressure of 2.4 kbar, indicating that the pressure-altered conformation of titin at 2.4 kbar is distinct to the GdmCl-denatured conformation. Pressure above 2 kbar apparently generated a flexible hydrophobic pocket for tryptophan residues of titin. PMID- 8203888 TI - Binding of heme-CO to bovine and porcine beta-lactoglobulins. AB - Two molecules of heme-CO bind to bovine or porcine beta-lactoglobulin (BLG) with an average affinity of 0.5 microM. The affinity increases with pH, with a transition near pH 7.5, indicating a conformational change in the protein. Heme CO does not bind to the predominantly alpha-helix conformation of BLG, which occurs in solutions with more than 40% ethanol or methanol. Fluorescence energy transfer measurements have been made for the complex of BLG with retinol and/or heme-CO. Two species of BLG were used. While bovine BLG possesses two tryptophans (at positions 19 and 61) which are quenched by about a factor of 2 by either retinol or heme-CO, the porcine species has only one tryptophan (at position 19) whose fluorescence is decreased by a factor of 15 when both hemes are bound, indicating that at least one of the heme-binding sites is near (< 20 A) to this tryptophan. The fluorescence of retinol (complexed to BLG) is also quenched by the addition of heme-CO, indicating that BLG can bind both molecules simultaneously; a separation of 25 A between retinol and heme was calculated. The results suggest at least two hydrophobic pockets for this protein. PMID- 8203889 TI - Zinc and other divalent cations inhibit purified leukotriene A4 hydrolase and leukotriene B4 biosynthesis in human polymorphonuclear leukocytes. AB - Leukotriene A4 hydrolase is a bifunctional metalloenzyme that contains 1 mol of zinc per mole of protein. The primary function of the metal is catalytic and zinc is thus necessary for both its peptidase and its epoxide hydrolase activity. However, at concentrations of zinc exceeding a 1:1 molar ratio (metal:enzyme), we found that zinc acted as an inhibitor with IC50 values of 10 microM for the epoxide hydrolase activity, i.e., the conversion of leukotriene A4 to leukotriene B4, and 0.1 microM for the peptidase activity. The inhibition of both enzyme activities could be reversed by treating the enzyme with chelating agents such as EDTA or dipicolinic acid. Several divalent cations, other than zinc, were also found to inhibit leukotriene A4 hydrolase although with different specificity and potency for the two enzyme activities. Thus, CdSO4 and HgCl2 were effective inhibitors (IC50 approximately 10 microM) of the epoxide hydrolase activity, whereas CoCl2 or MnCl2 were not inhibitory even at concentrations of 1 mM. On the other hand, the peptidase activity was inhibited by CdSO4, NiSO4, HgCl2, MnCl2, CoCl2, and PbNO3, listed in decreasing order of potencies (IC50 0.5-10 microM). In addition, zinc in micromolar concentrations inhibited leukotriene B4 formation in intact human polymorphonuclear leukocytes stimulated by the calcium ionophore A23187 and cell homogenates incubated with arachidonic acid. However, this effect was not related to inhibition of leukotriene A4 hydrolase but rather to a direct or indirect inhibitory effect on the enzyme 5-lipoxygenase in isolated leukocytes. In these cells, 15-lipoxygenase activity was also inhibited by zinc (IC50 5 microM), whereas leukotriene C4 synthase activity in human platelets and rat basophilic leukemia cells was significantly affected only at concentrations > or = 1 mM. PMID- 8203890 TI - Cloning and sequence of a cDNA encoding Akazara scallop troponin C. AB - A cDNA clone encoding troponin C of Akazara scallop (Chlamys nipponensis akazara) striated adductor muscle was isolated and sequenced. The cDNA is composed of 1987 bp and has an open reading frame of 462 bp at nucleotide positions 12-473. The amino acid sequence deduced from the cDNA showed 89% homology with that of Ezo giant scallop (Patinopecten yessoensis) troponin C (K. Nishita, H. Tanaka, and T. Ojima, 1994, J. Biol. Chem. 269, 3464-3468). However, it showed lower homology with those of troponin Cs from the other invertebrates (35-40%) and vertebrates (30%). A single functional Ca(2+)-binding site was found in site IV of the four potential Ca(2+)-binding sites as in the case of Ezo-giant scallop troponin C. Three amino acid deletions in the central D/E helix were required to align the scallop sequences with those of other troponin Cs. PMID- 8203891 TI - Structure-activity relationship for potentiation of EGF-dependent mitogenesis by oxygenated metabolites of linoleic acid. AB - Epidermal growth factor induces the oxygenation of linoleic acid in Syrian hamster embryo fibroblasts, and the lipoxygenase-derived products potentiate the mitogenic signal. We have further characterized the linoleate metabolites of growth factor-activated cells by chiral phase HPLC analysis. The primary product was identified as the pure (S) enantiomer of 13-hydroxyoctadecadienoic acid (HODE). In comparison to 13(R)-HODE isomer, only the biologically derived 13(S) HODE was active in augmenting DNA synthesis as assessed by [3H]thymidine incorporation. To extend these investigations, we defined the structural requirements of analogous lipid compounds necessary for stimulation of mitogenesis in these cells. Carbon-chain length, degree of unsaturation, type of oxidized functionality, position of oxygenated moiety, double-bond geometry, and chirality were all identified as factors that modulate the mitogenic activity of related compounds. The results demonstrate a high degree of specificity for (S) isomer hydro(pero)xylinoleic acid metabolites in stimulating DNA synthesis and further define the relationship between linoleic acid metabolism and growth factor-dependent cell growth. PMID- 8203892 TI - Comparative roles of histidine 51 in human beta 1 beta 1 and threonine 51 in pi pi alcohol dehydrogenases. AB - Histidine at position 51 of the class I beta 1 alcohol dehydrogenase (ADH) functions as a general base by indirectly abstracting a proton from the alcohol substrate through a hydrogen-bonded proton relay system. The human class II pi ADH was reported to be polymorphic, having either Ser or Thr, but not His at position 51. It is unknown whether Ser or Thr51 have a catalytic role in ethanol oxidation with pi-ADH. Accordingly, we expressed and purified recombinant mutants of pi-ADH with Thr, Ser, and His at position 51. At pH 6.5, values for Vmax/Km for ethanol were 0.30, 0.10, and 0.09 min-1 mM-1 for pi 51Thr, pi 51Ser, and pi 51His ADH, respectively. Hence the effects of the substitutions were much less than the 11-fold decrease in Vmax/Km observed for beta 1-ADH when a neutral amino acid (Gln) was substituted for His51. Addition of a buffer base (400 mM glycylglycine) had little effect on Vmax/Km of recombinant pi 51Thr or pi 51Ser ADH, while it increased Vmax/Km for ethanol 7-fold for the beta (1)51 Gln ADH. We conclude that there is no evidence for Thr51 of pi-ADH participating in a proton relay similar to that seen in beta 1-ADH and that a base at position 51 may not be a universal requirement for a functional alcohol dehydrogenase with a moderate efficiency for ethanol oxidation at a physiological pH. PMID- 8203893 TI - Cloning and regulation of rat tissue inhibitor of metalloproteinases-2 in osteoblastic cells. AB - Rat tissue inhibitor of metalloproteinases-2 (TIMP-2) was cloned from a UMR 106 01 rat osteoblastic osteosarcoma cDNA library. The 969-bp full-length clone demonstrates 98 and 86% sequence identity to human TIMP-2 at the amino acid and nucleic acid levels, respectively. Parathyroid hormone (PTH), at 10(-8) M, stimulates an approximately twofold increase in both the 4.2- and 1.0-kb transcripts over basal levels in UMR cells after 24 h of exposure. The PTH stimulation of TIMP-2 transcripts was not affected by the inhibitor of protein synthesis, cycloheximide (10(-5) M), suggesting a primary effect of the hormone. This is in contradistinction to regulation of interstitial collagenase (matrix metalloproteinase-1) by PTH in these same cells. Nuclear run-on assays demonstrate that PTH causes an increase in TIMP-2 transcription that parallels the increase in message levels. Parathyroid hormone, in its stimulation of TIMP-2 mRNA, appears to act through a signal transduction pathway involving protein kinase A (PKA) since the increase in TIMP-2 mRNA is reproduced by treatment with the cAMP analogue, 8-bromo-cAMP (5 x 10(-3) M). The protein kinase C and calcium pathways do not appear to be involved due to the lack of effect of phorbol 12 myristate 13-acetate (2.6 x 10(-6) M) and the calcium ionophore, ionomycin (10( 7) M), on TIMP-2 transcript abundance. In this respect, regulation of TIMP-2 and collagenase in osteoblastic cells by PTH are similar. However, we conclude that since stimulation of TIMP-2 transcription is a primary event, the PKA pathway must be responsible for a direct increase in transcription of this gene. PMID- 8203894 TI - Calcium indicator dye Quin2 inhibits hydrogen peroxide-induced DNA strand break formation via chelation of iron. AB - Exposure of HeLa cells to H2O2 at 4 degrees C caused DNA strand breakage which was prevented by the metal chelator 1,10-phenanthroline, but not by neocuproine. This is believed to indicate the participation of iron, rather than copper, in the formation of reactive hydroxyl radicals (.OH) from H2O2. The calcium indicator dye Quin2 also prevented H2O2-induced DNA fragmentation. The inhibition of oxidant-induced DNA fragmentation at 37 degrees C by Quin2 is often presented as evidence for the involvement of Ca(2+)-dependent endonucleases in damage. However, our finding that Quin2 inhibits DNA fragmentation at 4 degrees C led us to investigate the possibility that Quin2 may also inhibit DNA damage via its effects on metal-dependent .OH formation. Using ESR spin trapping techniques and in vitro DNA oxidation measurements, we found that the binding of Fe by Quin2 does not prevent .OH formation, but inhibits DNA damage. This is believed to reflect the prevention of iron ion binding to DNA by Quin2, directing .OH generation to the bulk solution, thereby preventing damage. The Cu-Quin2 complex was found to be a poor catalyst of both .OH formation and in vitro DNA damage. These findings suggest that the frequently reported protective effect of Quin2 toward DNA in cells exposed to oxidants may be due to the chelation of metal ions rather than the prevention of Ca(2+)-dependent endonuclease activation. PMID- 8203895 TI - Exposure of hydrophobic moieties promotes the selective degradation of hydrogen peroxide-modified hemoglobin by the multicatalytic proteinase complex, proteasome. AB - The physiologically relevant stress of a flux of H2O2 increased hemoglobin (Hb) degradation in red blood cells (RBC) and increased the proteolytic susceptibility of Hb in vitro. After exposure to low H2O2 flux rates (6-32 microM/min) Hb exhibited increased exposure of hydrophobic (Trp, Met) and basic (Lys) amino acid R groups, increased hydrophobicity, and increased proteolytic susceptibility during subsequent incubation with RBC extracts, a partially purified preparation called Fraction II (which retains all of the proteolytic activities of RBC extracts), or the purified 670-kDa RBC multicatalytic proteinase complex proteasome. Hydrophobicity was measured by butyl-Sepharose hydrophobic interaction chromatography, by the free energy of transfer from water to ethanol, and by heat denaturation assays. Proteolytic susceptibility was measured by release of free alanine, by fluorescamine-reactive free amino groups, and by release of acid-soluble radioactivity from radiolabeled Hb. Low H2O2 flux rates also caused significant charge changes in Hb (isoelectric focusing gels) and extensive noncovalent aggregation (presumably due to increased hydrophobic interactions) but only limited covalent cross-linking (comparison of sodium dodecyl sulfate-polyacylamide gel electrophoresis (SDS-PAGE) and nondenaturing PAGE). Exposure to higher H2O2 flux rates (56-120 microM/min) caused progressive oxidative destruction of exposed hydrophobic amino acids, decreased hydrophobicity as judged by butyl-Sepharose chromatography and heat denaturation assays, increased hydrophilicity as judged by measurements of the free energy of transfer (delta G') from water to ethanol, and decreased proteolytic susceptibility during incubation with RBC extracts, Fraction II, or purified proteasome. High H2O2 flux rates also caused further charge changes and the extensive formation of covalently cross-linked Hb molecules. Linear regression analyses revealed correlations of 0.8-0.99 for the relationship between Hb hydrophobicity and proteolytic susceptibility for both Fraction II and proteasome. Inhibitor studies and SDS activation experiments indicate that proteasome is responsible for most of the Hb degradation during exposure of RBC to H2O2. Previous work yielded essentially identical conclusions for Hb exposed to hydroxyl radicals (R. E. Pacifici, Y. Kono, and K. J. A. Davies, J. Biol. Chem. 268, 15405-15411, 1993). Thus, nonspecific oxidation by .OH and site specific (metal-catalyzed) oxidation by H2O2 both yield a more hydrophobic Hb molecule with increased proteolytic susceptibility. We propose that increased exposure of hydrophobic, and perhaps basic, amino acids is the general common cause for degradation of oxidized proteins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8203896 TI - Human liver microsomes are efficient catalysts of 1,3-butadiene oxidation: evidence for major roles by cytochromes P450 2A6 and 2E1. AB - Previously, we provided evidence for the involvement of multiple cytochrome P450 enzymes in the metabolism of 1,3-butadiene, a rodent and possibly a human carcinogen, to butadiene monoxide in mouse and rat liver microsomes. In this study, 1,3-butadiene oxidation by seven cDNA-expressed human P450 enzymes and by human, mouse, and rat liver microsomes was characterized. Incubations with cDNA expressed human P450 1A2, 2A6, 2B6, 2D6, and 2E1 resulted in the formation of butadiene monoxide, whereas incubations with P450 1A1 and 3A4 did not lead to the detection of any metabolite. Of the active isozymes examined, P450 2A6 and 2E1 were the most active when butadiene monoxide formation rates were normalized for the P450 content of the microsomes. With six human liver microsomal samples, 1,3 butadiene oxidation exhibited nearly threefold individual variation in the amounts of butadiene monoxide detected, and butadiene monoxide formation was NADPH- and time-dependent and was inhibited by the addition of 1-benzyl-imidazole or 4-methylpyrazole, known cytochrome P450 inhibitors. Correlation studies provided evidence for major roles by P450 2A6 and 2E1 in 1,3-butadiene oxidation in human liver microsomes. Butadiene monoxide formation rates in human liver microsomes were similar, or higher, than the rate obtained in mouse liver microsomes, whereas 1,3-butadiene oxidation rates in human and mouse liver microsomes were higher than the rate obtained in rat liver microsomes. These results provide direct evidence that 1,3-butadiene is a substrate for multiple P450 enzymes and suggest that humans may be at higher risk of expressing 1,3 butadiene toxicity compared to mice or rats. In addition, these results suggest that the mouse may be the more appropriate animal model to assess human risk. PMID- 8203897 TI - Stimulation of acid ceramidase activity by saposin D. AB - Ceramide is ubiquitously present in plasma membranes and plays a pivotal role in metabolism of sphingolipids. In addition, ceramide and its hydrolytic product, sphingosine, may have important roles as second messengers for cell function and survival. Ceramide is hydrolyzed by both acid and alkaline ceramidase. In this investigation, saposin D was found to stimulate the acid, but not the alkaline, ceramidase. With a crude membrane enzyme preparation, the stimulation was about fourfold. Saposin D is one of four saposins (sphingolipid activator proteins) that are derived from a single precursor protein, prosaposin. Saposins, A, B, and C had no significant effect on ceramidase activity. A kinetic study showed that the stimulation by saposin D was caused by decreasing its Km value for ceramide without a significant change in its Vmax value. A binding study demonstrated that saposin D, as well as saposins A, B, and C, binds to ceramide at neutral pH but not at acidic pH. Preliminary evidence suggests that partially purified acid ceramidase contains bound saposin D. These findings suggest that saposin D facilitates acid ceramidase activity primarily by interaction with the enzyme. The function of saposin D as a modulator of ceramide concentration in vivo has been suggested by the accumulation of ceramide in tissues of patients with total saposin deficiency. PMID- 8203898 TI - Biochemical characterization of the interaction of lipid phosphoric acids with human platelets: comparison with platelet activating factor. AB - A series of lipid phosphoric acids, including 1-O-alkyl-2-lyso-glycerophosphoric acid, 1-O-acyl-2-lyso-glycerophosphoric acid, hexadecylpropanediolphosphoric acid, N-acyl-2-aminoethanolphosphoric acid, sphingosine phosphoric acid, and certain homologues and analogues, were synthesized and characterized by thin layer chromatography, fast-atom bombardment mass spectrometry, and their ability to aggregate human platelets. The presence of a receptor for these lipid phosphoric acids that is distinct from the PAF receptor is strongly suggested from experiments involving a desensitization procedure, platelet-activating factor (PAF) receptor antagonists, and inhibitors of the lipid phosphoric acids. The unique features of the interaction of these lipid phosphoric acids with platelets include: (a) evidence for a separate receptor(s) for this diverse group of synthetic compounds, (b) no requirement for stereospecificity (i.e., no glycerol backbone), and (c) a structural requirement for a long-chain hydrocarbon residue covalently bound to a phosphoric acid residue. In the interaction of these compounds with the platelet, it is mandatory that extracellular Ca2+ and ADP be present for maximum biological activity. The potential involvement of a lipid phosphoric acid receptor, which could form a component of the activation pathway associated with various lysophospholipids and analogues, such as PAF, via a phospholipase D activation, is discussed. PMID- 8203899 TI - Prochiral sulfoxidation as a probe for multiple forms of the microsomal flavin containing monooxygenase: studies with rabbit FMO1, FMO2, FMO3, and FMO5 expressed in Escherichia coli. AB - Multiple forms of the microsomal flavin-containing monooxygenase (FMO) exist in rabbit tissues. In order to better understand the catalytic properties of these isoforms, we have expressed rabbit FMO1, FMO2, FMO3, and FMO5 in Escherichia coli and examined their kinetic parameters and prochiral selectivities for the sulfoxidation of methyl-, ethyl-, n-propyl-, and n-butyl-substituted p-tolyl sulfides. FMO1 and FMO2 exhibited high affinities for these substrates (Km < 10 microM), in contrast to the low-affinity FMO3 form for which Km values ranged between 100 and 280 microM. FMO5 did not form quantifiable levels of sulfoxide metabolites at the concentrations used. The individual stereochemical metabolite profiles generated by FMO1, FMO2, and FMO3 were unique and served to distinguish among these three cDNA-expressed isoforms. To investigate the relationship between the kinetic parameters for the cDNA-expressed enzymes and the native microsomal enzymes, we examined the kinetics and stereoselectivity of metabolism of methyl p-tolyl sulfide by detergent-solubilized rabbit liver microsomes. We analyzed these data with respect to FMO1 and FMO3, the two predominant hepatic isoforms. Sulfoxidation of methyl p-tolyl sulfide by FMO1 and FMO3 solubilized from E. coli microsomes proceeded with apparent Kms of 18 and 270 microM, respectively. FMO1 was essentially stereospecific for formation of (R)-methyl p tolyl sulfoxide, whereas FMO3 generated this metabolite with little prochiral selectivity. Sulfoxidation of methyl p-tolyl sulfide by detergent-solubilized rabbit liver microsomes was best described by a two-enzyme model, with apparent Km values of 11 and 340 microM. The enantiomeric purity of the (R)-methyl p-tolyl sulfoxide metabolite, generated by detergent-solubilized rabbit liver microsomes, decreased progressively with increasing substrate concentration, from a high of 96% enantiomeric excess at a substrate concentration of 5 microM to a low of 63% enantiomeric excess at a substrate concentration of 2 mM. The kinetic and stereochemical properties of the high-affinity and low-affinity components of detergent-solubilized rabbit liver microsomes were similar to those exhibited by cDNA-expressed FMO1 and FMO3, respectively. Therefore, methyl p-tolyl sulfide, used at the appropriate substrate concentrations, is useful for discriminating between FMO1- and FMO3-mediated catalysis in rabbit liver microsomal preparations. PMID- 8203900 TI - Effect of superoxide and superoxide dismutase on lignin peroxidase-catalyzed veratryl alcohol oxidation. AB - We have shown that superoxide (O2.-) is produced during the oxidation of veratryl alcohol by lignin peroxidase (LiP) by the reaction of the veratryl alcohol cation radical with hydrogen peroxide (D. B. Barr, M. M. Shah, and S. D. Aust, 1993, J. Biol. Chem. 268, 241-244). Compound III, an inactive form of peroxidases can be formed by reaction of the ferric enzyme with O2.-. We therefore studied the effects of O2.- and superoxide dismutase (SOD) on the veratryl alcohol oxidase activity of LiP. SOD enhanced the rate of veratryl alcohol oxidation by LiP and veratryl alcohol oxidation was inhibited by the addition of KO2. Upon the addition of KO2, activity was also preceded by a lag period. Under steady-state turnover conditions (i.e., for veratryl alcohol oxidation), the addition of KO2 resulted in the formation of LiP compound III. Compound II of LiP was observed following a time period that correlated with the lag prior to veratryl aldehyde formation. The extent of the lag preceding veratryl aldehyde formation increased with increasing concentrations of KO2 and decreased with increasing concentrations of veratryl alcohol. It was postulated that during the lag period the veratryl alcohol cation radical reacted with compound III to regenerate the native enzyme. In this process the veratryl alcohol cation radical was reduced to veratryl alcohol, and thus, no veratryl aldehyde was detected during the lag period. PMID- 8203901 TI - 1H NMR determination of intracellular volume in cell suspensions. AB - A 1H NMR method has been developed for determining the intracellular and extracellular volumes in a cell suspension. The method is quick, simple, and inexpensive. A comparison of the ratios of the water and Tris buffer resonances in a cell suspension and in a buffer solution gives the intracellular volume. The most important precaution to take is to ensure that coil loading is identical in both solutions and that the NMR signal is not saturating. The method was validated with a 20% polyethylene glycol solution. A comparison with radiolabel methods for volume determination found that the radiolabel probe of extracellular volume did not penetrate the cell wall water of Enterococcus faecalis, resulting in an overestimation of the intracellular volume, and that tritiated water probably exchanged with macromolecules, causing an underestimation of intracellular volume. PMID- 8203902 TI - Use of photoreactive substrates for characterization of lysophosphatidate acyltransferases from developing soybean cotyledons. AB - Photoreactive lipid analogs, namely, 1-acyl-2-(12-azidooleoyl)glycero-3 phosphocholine (N3-PC) and 1-acyl-2-(12-azidooleoyl)glycero-3-phosphoethanolamine (N3-PE) have been synthesized as previously described [R. Rajasekharan and J. D. Kemp (1994) J. Lipid Res. 35, 45-51]. Azidophosphatidic acid was produced by hydrolyzing N3-PC with phospholipase D. All of the lysophospholipid analogs, 2 (12-azidooleoyl)glycero-3-phosphate (N3-LPA), 2-(12-azidooleoyl)glycero-3 phosphocholine (N3-LPC), and 2-(12-azidooleoyl)glycero-3-phosphoethanolamine (N3 LPE), were produced from appropriate azidophospholipids by lipase treatment. The photoactive lysophospholipid analogs were recognized as substrates by acyltransferases in the dark and as irreversible inhibitors after photolysis with uv light. The photoinactivation of acyltransferases by azidolysophospholipids was protected by the addition of natural lysophospholipids. Incubation of developing soybean microsomal membranes with N3-LPA followed by photolysis resulted in 69% inhibition of lysophosphatidic acid (LPA) acyltransferase and also had significant inhibitory effects on lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) acyltransferases, indicating that the LPA analog interacts with all the lysophospholipid acyltransferases. When the membranes were photolyzed with N3-LPC or N3-LPE and assayed, the membranes showed approximately 50% inactivation of LPC and LPE acyltransferase activities, whereas LPA acyltransferase was unaffected, suggesting that a single enzyme might acylate both LPC and LPE. The recognition of these photoreactive lipid analogs by acyltransferases will facilitate the identification and purification of these membrane-bound enzymes. PMID- 8203903 TI - Characterization of monkey cytochrome P450, P450 CMLd, responsible for S mephenytoin 4-hydroxylation in hepatic microsomes of cynomolgus monkeys. AB - We isolated a new form of cytochrome P450 (P450) which was able to catalyze S mephenytoin 4'-hydroxylation from hepatic microsomes of cynomolgus monkeys. The final preparation (referred to as P450 CMLd) was apparently homogenous judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and the estimated minimum molecular weight of this protein was 53 kDa. The N-terminal amino acid sequence of P450 CMLd (identified 16 residues) was identical with that of protein encoded by P450 2C9 cDNA. P450 CMLd was cross-reactive with both antibodies raised against P450 2C11 and P450 2C9 which were purified from hepatic microsomes of male rats and humans, respectively. In hepatic microsomes of cynomolgus monkeys, both antibodies recognized two proteins showing different mobilities on SDS-PAGE (50 and 53 kDa). P450 CMLd was a good catalyst for S mephenytoin 4'-hydroxylation in a reconstituted system. Anti-P450 2C9 antibody inhibited the activity of S-mephenytoin 4'-hydroxylase, but not the activities of R-mephenytoin 4'-hydroxylase and R- and S-mephenytoin N-demethylases in liver microsomes from cynomolgus monkeys. From these lines of evidence we conclude that P450 CMLd is classified into the P450 2C subfamily and acts as one of the S mephenytoin 4'-hydroxylases in hepatic microsomes of cynomolgus monkeys. PMID- 8203904 TI - Purification and enzymatic properties of a recombinant fusion protein expressed in Escherichia coli containing the domains of bovine P450 17A and rat NADPH-P450 reductase. AB - A fusion protein containing the heme domain of bovine cytochrome P450 17A and the flavin domains of rat NADPH-cytochrome P450 reductase has been genetically engineered by linking the modified cDNAs for each gene with the codons for serine and threonine. Transformation of Escherichia coli (DH5 alpha) and growth under defined conditions permits expression of 600-700 nmol of membrane-bound fusion protein per liter of growth medium (approximately 4% of cellular protein). A method has been developed for the solubilization, isolation, and purification to homogeneity of this protein. In the presence of NADPH the purified fusion protein catalyzes the 17 alpha-hydroxylation of progesterone and pregnenolone as well as the conversion of 17 alpha-hydroxypregnenolone to dehydroepiandrosterone. The 17,20-lyase activity is enhanced sixfold by the addition of purified rat liver cytochrome b5. Further, dehydroepiandrosterone is slowly metabolized to a number of additional more polar metabolites while 17 alpha-hydroxy-progesterone is slowly converted to dihydroxy-progesterone metabolites as well as a small amount of androstenedione in a reaction not influenced by cytochrome b5. Use of 5 alpha pregnan steroids as substrates show the importance of the 3 beta-hydroxyl group for cytochrome b5 stimulated 17,20-lyase activity. Studies investigating the factors affecting electron transport between the flavin and heme domains suggest that the protein exists as a tight complex functioning as a self-contained biocatalytic unit. PMID- 8203905 TI - Interaction of the catalytic and the membrane subunits of an oxyanion translocating ATPase. AB - Resistance to arsenical and antimonial compounds in Escherichia coli is due to active extrusion of these compounds from cells expressing the ars operon. The arsenical pump is an ion-translocating ATPase which consists of two polypeptide components, the ArsA and ArsB proteins. The ArsB protein, the inner membrane component of the pump, has been shown to function as the membrane anchor for the catalytic subunit, the ArsA protein. The properties and nature of interaction between these two components of the pump were investigated using an in vitro binding assay. Purified ArsA protein bound to the membrane in a saturable manner. In the absence of arsenite or antimonite an apparent positive cooperativity in the binding of the ArsA protein to membrane vesicles containing the ArsB protein was observed. In the presence of arsenite or antimonite binding became hyperbolic, with a 10-fold decrease in the concentration of ArsA protein required for half-maximal binding, without any change in the stoichiometry of the complex. Addition of ATP had little affect on membrane binding of the ArsA ATPase subunit. In the presence or absence of the anionic substrates binding was maximal in a pH range 7.5-8.5. PMID- 8203906 TI - Hydrogen peroxide regulates phospholipase D-mediated hydrolysis of phosphatidylethanolamine and phosphatidylcholine by different mechanisms in NIH 3T3 fibroblasts. AB - A major goal of this work was to determine in NIH 3T3 fibroblasts whether the recently described effects of H2O2 on phospholipase D-mediated hydrolysis of phosphatidylethanolamine (PtdEtn) and phosphatidylcholine (PtdCho) are mediated by similar or different mechanisms. While exposure of NIH 3T3 fibroblasts to H2O2 stimulated the hydrolysis of both PtdEtn and PtdCho, the following important differences were noted: (i) prolonged (24 h) treatment of fibroblasts with 400 nM phorbol 12-myristate 13-acetate (PMA) blocked the stimulatory effect of H2O2 on PtdEtn, but not on PtdCho, hydrolysis; (ii) PMA-induced hydrolysis of PtdEtn, but not PtdCho, was inhibited by H2O2; (iii) the stimulatory effect of H2O2 was additive with that of sphingosine or staurosporine, inhibitors of protein kinase C, on the hydrolysis of PtdCho, but not PtdEtn; (iv) with membranes isolated from H2O2-treated fibroblasts, the hydrolysis of PtdCho, but not PtdEtn, was increased compared to values obtained with control membranes. These results imply that H2O2 regulates PtdEtn and PtdCho hydrolysis by different mechanisms. Stimulation of PtdEtn hydrolysis by H2O2, sphingosine, and staurosporine may commonly involve, at least in part, neutralization of an inhibitory protein kinase C isozyme. PMID- 8203907 TI - Evaluation of triacetyloleandomycin, alpha-naphthoflavone and diethyldithiocarbamate as selective chemical probes for inhibition of human cytochromes P450. AB - A variety of chemicals, including triacetyloleandomycin (TAO), alpha naphthoflavone (ANF), and diethyldithiocarbamate (DDC), are widely used as inhibitory probes for select individual human cytochrome P450 (CYP) enzymes, despite the fact that the selectivity of these inhibitors has not been rigorously evaluated. In the present study we take advantage of recent advances in cDNA directed human P450 expression to evaluate directly the P450 form selectivity of TAO, ANF, and DDC, using a panel of 10 individual cDNA-expressed human P450s. Under experimental conditions known to yield maximal TAO complexation with P450 hemoproteins, TAO (20 microM) inhibited the catalytic activity of expressed CYPs 3A3, 3A4, and 3A5, whereas it did not affect CYPs 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, or 2E1 activity. ANF inhibited not only CYPs 1A1 and 1A2 (IC50 = 0.4-0.5 microM), but it was also similarly effective against CYPs 2C8 and 2C9. Increasing the concentration of ANF to 10 microM led to inhibition of CYP2A6 and CYP2B6. Although a previous study suggested that DDC is a selective inhibitor of CYP2E1, the present investigation shows that at concentrations required to inhibit CYP2E1 (IC50 approximately 125 microM when preincubated with NADPH), DDC also inhibited CYPs 1A1, 1A2, 2A6, 2B6, 2C8, 3A3, and 3A4. Decreasing the concentration of DDC to 10 microM, however, led to inhibition of CYP2A6 (65% inhibition) and CYP2B6 (50% inhibition), but none of the other P450s examined, including CYP2E1. Overall, these results establish that (a) TAO is a selective inhibitor of the human CYP3A subfamily; (b) ANF potently inhibits CYP2C8 and CYP2C9, in addition to CYPs 1A1 and 1A2; and (c) DDC cannot be employed as a diagnostic inhibitory probe for CYP2E1. PMID- 8203908 TI - Primary structure of human liver glycogen synthase deduced by cDNA cloning. AB - The cDNA for human liver glycogen synthase was isolated by screening a human liver cDNA library constructed in lambda gt11. The full cDNA was 2912 bp in length. It coded for a protein of 703 amino acid residues with a molecular mass of 80.9 kDa. The number of amino acids was identical to and the deduced amino acid sequence homology was 92% that of the rat liver enzyme. The human and rat liver glycogen synthases are truncated by 34 amino acids compared to the human muscle enzyme, and by 32 amino acids compared to the rabbit muscle enzyme. The amino acid similarity between human liver and human muscle glycogen synthase was only 69%. It was least similar in the N and C terminal regions of the molecule. Two highly conserved regions are present in all published amino acid sequences for glycogen synthase, including those of the two yeast enzymes. These regions include the amino acid sequences from 201 to 400 and 501 to 600. This high conservation suggests that the catalytic site and the glucose-6-P and nucleotide allosteric sites are included in these regions. PMID- 8203909 TI - The inactivation of sheep liver sorbitol dehydrogenase by pyrophosphate and some analogous metal chelators. AB - Pyrophosphate and several other metal chelators are shown to inactivate sheep liver sorbitol dehydrogenase. Pyrophosphate, tripolyphosphate, and some bisphosphonates inactivate the enzyme by saturation kinetics involving the formation of a reversible complex. A mechanism for the pyrophosphate-mediated inactivation of sorbitol dehydrogenase is proposed. Steady-state kinetics show that pyrophosphate does not compete with sorbitol for binding to the catalytic zinc atom or with NAD for binding to the anion binding site. The latter is supported by the formation of an E-NAD-pyrophosphate (PPi) complex and by the noncompetitive protection of NADH against inactivation. The rate of enzyme inactivation by pyrophosphate increases with decreasing pH. The pH dependence of the inactivation indicates that a group with a pKa of 6.9 in the free enzyme and in the enzyme-PPi complex is involved. As several zinc-binding reversible inhibitors do not afford protection against pyrophosphate inactivation, the pKa values obtained are considered not to refer to the ionization of the zinc-bound water molecule, but are tentatively suggested to be those of an active site histidine residue. Protection and reactivation by Zn2+ ions indicate that enzyme inactivation results from the loss of the catalytic zinc atom. PMID- 8203910 TI - The fate of the carboxyl oxygens during D-proline reduction by clostridial proline reductase. AB - D-Proline is converted to 5-amino valeric acid by D-proline reductase. This conversion involves the reductive cleavage of the alpha-carbon-nitrogen bond. We have examined the fate of the carboxyl oxygen atoms during conversion of D proline to delta-NH2-valeric acid. 18O atoms from the carboxyl group of D-proline are not lost during conversion to product. In contrast, in the conversion of glycine to acetyl phosphate by glycine reductase a carboxyl oxygen atom is lost to solvent. An intermediate acyl-enzyme is found during the reduction of glycine. We conclude that the reduction of proline proceeds without the formation of an acyl enzyme intermediate. PMID- 8203911 TI - Identification of a lipid transfer protein as the major protein in the surface wax of broccoli (Brassica oleracea) leaves. AB - Presence of proteins in the surface wax of plants has been noted but no protein has been identified heretofore. A 9-kDa protein was purified as the major protein from the surface wax of broccoli (Brassica oleracea var. italica) leaves and the N-terminal amino acid sequence was determined. A cDNA corresponding to the wax associated protein, designated WAX9, was sequenced revealing an open reading frame that codes for an 11.9-kDa polypeptide of 118 amino acids including a 25 amino acid leader peptide. The amino acid sequence showed 40 to 50% identity with nonspecific lipid transfer proteins isolated from various plants. Northern blots showed that a wax9 transcript of 650 nucleotides was highly expressed in leaves, stems, and flower buds and only at a reduced level in open flowers and not in roots. The transcript level decreased as the leaf fully expanded. The results suggest that the wax9 gene is expressed at the highest level at the time of maximal synthesis of the surface wax. Immunogold labeling studies showed that the WAX9 protein was present mainly in the cell wall of the epidermis and mesophyll tissues as well as in the phloem. However, immunological measurements showed that 50 and 4% of the total WAX9 was in the surface wax in the young and old leaves, respectively. Since immunogold labeling method would involve the loss of the surface wax, it would not detect the WAX9 protein in the wax. Thus, the present results reveal for the first time that a major portion of lipid transfer protein is in the surface wax. PMID- 8203912 TI - Developmentally regulated oligosaccharides in mouse spermatogenic cells. AB - Mouse spermatogenic cells were separated into four populations, pachytene spermatocytes, round spermatids, elongated spermatids, and residual bodies. Each cell population was metabolically labeled with [3H]galactose, [3H]glucosamine, or [3H]fucose. Glycopeptides were prepared from the radiolabeled glycoproteins by pronase digestion and fractionated by serial lectin affinity chromatography and gel filtration. The presence of O-linked oligosaccharides was assessed by pronase digestion of [3H]galactose-labeled glycoproteins, exclusion of the radiolabeled glycopeptides from a ConA-Sepharose column, gel filtration, and treatment with alkaline borohydride. This analysis reveals that a large proportion of [3H]galactose-labeled oligosaccharides (47-52%) are O-linked structures, while the majority (80-90%) of [3H]fucose-labeled oligosaccharides are N-linked. The proportions of triantennary, biantennary, oligomannose, and hybrid oligosaccharides linked to asparagine vary with the cell populations. Furthermore, in round spermatids, but not in the other cell populations, a relatively large proportion (15%) of [3H]glucosamine-labeled oligosaccharides consists of terminal O-linked N-acetylglucosamine. Taken together these data show that each spermatogenic cell population contains a unique complement of oligosaccharide structures that could play an important role as differentiation signals in the interactions among these cells and/or with Sertoli cells. PMID- 8203913 TI - A functional heterologous electron-transfer protein complex: Desulfovibrio vulgaris flavodoxin covalently linked to spinach ferredoxin-NADP+ reductase. AB - The water-soluble carbodiimide, N-ethyl-3-(3-dimethylaminopropyl)carbodiimide was found to readily promote formation of cross-links between spinach ferredoxin NADP+ reductase and bacterial flavodoxins. The covalent complex between ferredoxin-NADP+ reductase and the Desulfovibrio vulgaris flavodoxin had a stoichiometry of 1 mol of flavodoxin per mole of the reductase, as assessed by denaturing electrophoresis, gel filtration and spectral analysis. The reductase moiety of the cross-linked complex gained the capacity to catalyze at a high rate the electron transfer from NADPH to cytochrome c without addition of free flavodoxin in the assay. The pH optimum for this activity was shifted to the alkaline region with respect to that for the noncovalent complex. FMN, the prosthetic group of flavodoxin, is required for electron transfer from the reductase FAD to cytochrome c. Structural studies carried out on the cross-linked complex allowed the identification of the peptide regions of the proteins involved in the interaction. The CNBr peptide 61-155 of the reductase was found cross-linked to the uncleaved flavodoxin, while the cross-linked region in flavodoxin appeared to be within the tryptic peptide 37-86. Treatment of flavodoxin with the carbodiimide in the presence of glycine ethyl ester brought about the modification of a few carboxyl groups and prevented its interaction with the reductase. It can be concluded that the bacterial flavodoxin binds to the reductase in a way similar to that of the physiological substrate ferredoxin (G. Zanetti, D. Morelli, S. Ronchi, A. Negri, A. Aliverti, and B. Curti, 1988, Biochemistry 27, 3753-3759). The cross-linked complex here described represents an useful model for studying electron transfer between the two flavoproteins. PMID- 8203914 TI - A comparison of the enzymatic and physicochemical properties of human glutathione transferase M4-4 and three other human Mu class enzymes. AB - The multigene family of cytosolic glutathione S-transferases (GSTs) consists of four classes (Alpha, Mu, Pi, and Theta), all involved in the detoxication of reactive electrophiles. The human Mu class GSTs consist of at least four expressed isozyme subunits, GST M1, GST M2, GST M3, and GST M4, which have 70-90% amino acid sequence identity. The gene and cDNA sequences for GST M4 have been determined recently (K. E. Comstock, K. J. Johnson, D. Rifenbery, and W. D. Henner, J. Biol. Chem. (1993) 268, 16958-16965). Cloning of GST M4 cDNA into an Escherichia coli expression system permitted the production of the corresponding protein. The enzyme was purified and shown to have a relatively low specific activity with the standard GST substrate 1-chloro-2,4-dinitrobenzene (1.4 +/- 0.2 mumol min-1 mg-1 protein), but an activity equivalent to other Mu class enzymes with other tested substrates. The protein forms functional dimers composed of subunits with a M(r) of approximately 26,400. A detailed comparison of the activity with various substrates and inhibitors was performed between GST M4-4 and other human Mu class GSTs, GST M1a-1a, GST M2-2, and GST M3-3, produced in bacterial expression systems. Despite the high level of amino acid sequence identity, the enzymatic properties of these enzymes were quite different. Comparisons with the crystallographic structure of a homologous rat GST, GST 3-3, indicate that a number of the nonconserved amino acid residues can be assigned to the putative active site of GST M4-4. This suggests that diversification in the evolution of these genes has occurred primarily in the substrate binding regions to cope with an increasing variety of foreign compounds. PMID- 8203915 TI - Purification, characterization, and cloning of alpha-hydroxynitrile lyase from cassava (Manihot esculenta Crantz). AB - alpha-Hydroxynitrile lyase (HNL, acetone cyanohydrin lyase, EC 4.1.2.37) was purified to homogeneity from young leaves of the cyanogenic tropical crop plant cassava (Manihot esculenta Crantz). The purified protein is a homo-trimer with a subunit relative molecular mass of 28,500 on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The active protein is not glycosylated and does not contain a flavin group. HNL exhibits complex kinetics which vary according to substrate concentration and may be related to aggregation of the enzyme. HNL activity against two natural substrates, acetone cyanohydrin and 2 butanone cyanohydrin, and one nonphysiological substrate, 2-pentanone cyanohydrin, was demonstrated. N-terminal and internal peptide sequences, obtained from HNL digested with the endoproteinase Glu-C, were used to design degenerate oligonucleotide primers for polymerase chain reaction with single strand cDNA, using purified mRNA from cotyledons as template. The resulting DNA fragment was used to probe a cassava cotyledon cDNA library. Four cDNA clones were isolated, sequenced, and shown to contain derived amino acid sequences identical to those obtained from the purified protein. PMID- 8203916 TI - Substrate activity of Rh(III)ATP with phosphoglycerate kinase and the role of the metal ion in catalysis. AB - An exchange-inert Rh(H2O)4ATP complex showed a one-turnover substrate activity with yeast phosphoglycerate kinase. Transfer of the phosphoryl group between ATP and 3-phosphoglycerate occurs with both substrates in the coordination sphere of the metal ion. Because of the slow ligand exchange rates of Rh3+, the reaction product 1,3-diphosphoglycerate (1,3-dPGA) remained coordinated to the metal ion. During the course of the reaction, the enzyme was inactivated, suggesting that the metal ion is coordinated to a protein side chain. Thus the product Rh(H2O)nADP.1,3-dPGA remained bound to the enzyme even after removal of excess substrate. These results suggested that the metal ion may not only act as an electron sink to activate the electrophile, but it may also help to optimally align both substrates for phosphoryl transfer by coordination to both substrates. It is therefore likely that entry of 3-phospho-D-glycerate into the coordination sphere of metal of a metal-ATP complex may start the proposed hinge-bending motion of yeast phosphoglycerate kinase to form a "closed" active site between the two substrate binding domains of the enzyme. PMID- 8203917 TI - Initial kinetic and mechanistic characterization of Escherichia coli fumarase A. AB - The protein encoded by the fumA gene in Escherichia coli is shown herein to be a highly efficient and specific catalyst of the fumarase reaction. In an investigation of 21 substrate analogs, this protein only had substantial activity as a hydro-lyase on fumarate, malate, acetylene dicarboxylate, fluorofumarate, and 2(S),3(S)-tartrate. The kcat and kcat/Km for the hydration of fumarate by this protein are 3100 s-1 and 5 x 10(6) mol-1 s-1, respectively. It is likely that one physiological role of this protein is a catalyst of the fumarase reaction; therefore, it is appropriate to name it fumarase A. Fumarase A specifically removes the 3-pro-R in the dehydration of (2S)-malate. The product of the action of fumarase A on acetylene dicarboxylate, fluorofumarate and 2(S),3(S)-tartrate is oxalacetate. The nitronate form of 2-hydroxy-3-nitro propionate is a potent inhibitor of fumarase A, implying that the enzyme forms an intermediate with an anion at C-3. No kinetic isotope effect was found with (2S,3R)-3-[2H]malate. The effects of pH on the kcat and kcat/Km for fumarate as a substrate show that the pKas of the groups involved in catalysis differ markedly from porcine fumarase. The possible roles of the proteins encoded by the three fumarase genes in E. coli are briefly discussed. PMID- 8203918 TI - Overexpression of iron-responsive element-binding protein and its analytical characterization as the RNA-binding form, devoid of an iron-sulfur cluster. AB - The iron-responsive element-binding protein (IRE-BP) has been defined and identified as an RNA-binding protein found in iron-deprived eukaryotic cells. IRE BP binds to stem-loop structures, iron-responsive elements (IREs), which are located in the untranslated regions of the mRNAs for several genes including ferritin, and the transferrin receptor. When bound, IRE-BP prevents ferritin translation and stabilizes the transferrin receptor transcript. When cells are iron replete, an iron-sulfur cluster is ligated to the IRE-BP, the protein loses RNA binding properties, and it acquires aconitase activity. Cytosolic aconitase from liver can be converted into the IRE-BP by oxidative removal of its Fe-S cluster. We describe here overexpression of IRE-BP in baculovirus-infected insect cells which yields IRE-BP devoid of an iron-sulfur cluster. We describe a one step purification of the IRE-BP and a quantitative analysis of Fe, S2-, S0, protein, and enzyme activity on IRE-BP, as obtained in cell lysates, after purification, and after reconstitution to active aconitase. On the average not more than 3% of the over-expressed purified protein contained an intact Fe-S cluster, and it was demonstrated that that cluster was not lost during purification. Scatchard analysis of RNA-binding data was compatible with a single high-affinity RNA-binding form of the IRE-BP. Active aconitase could be reconstituted from the purified IRE-BP obtained from the expression system by addition of iron, thiol, and sulfide, and the characteristic epr spectrum of the 3Fe form of cytosolic aconitase was obtained after ferricyanide oxidation of the reconstituted material. PMID- 8203919 TI - 8-Hydroxyguanine is not produced by permanganate oxidation of DNA. AB - Single-stranded M13mp2 DNA was oxidized with 0.8 mM KMnO4 at pH 8.6 and 4 degrees C for 5 min. These are conditions used previously by Akman et al. (Arch. Biochem. Biophys., 1990, 282, 202) for the oxidation of a denatured DNA and the authors reported that 8-hydroxyguanine was formed in the DNA with this treatment. We decomposed the oxidized DNA with heating in formic acid and the resulting bases were analyzed by HPLC. No significant 8-hydroxyguanine formation was detected in this sample. We also investigated the consumption of KMnO4 by nucleosides. Under conditions in which thymidine consumed KMnO4 rapidly, very little consumption was found with deoxyguanosine (less than 1/100, in rate, compared to that by thymidine). These results show that the permanganate oxidation of DNA does not result in the formation of 8-hydroxyguanine. PMID- 8203920 TI - [DNA stemline heterogeneity as preoperative prognostic factor in esophageal cancer]. AB - Flow cytometric nuclear DNA analysis was performed on 36 preoperative endoscopic biopsy specimens and 89 surgically resected specimens of esophageal carcinomas without preoperative radiotherapy. Carcinomas with aneuploid or DNA stem-line heterogeneity had a higher frequency of lymph node metastasis (p < 0.01). The correspondence rate of nuclear DNA ploidy patterns was 97% between biopsy and resected specimens, and that of heterogeneity was 72%. Though only six cases showed heterogeneity in biopsy specimens out of 12 cases which showed heterogeneity in resected specimens, preoperative detection of heterogeneity was supposed to be more accurate by an increase of biopsy specimens. DNA analysis of biopsy specimens may be a possible indicator of the malignant potential of esophageal carcinoma. PMID- 8203921 TI - [MultiCycle software for cell cycle analyses]. AB - MultiCycle software (M-cycle), a computer cell cycle analysis program that has a background debris and aggregation compensating function, was utilized in this study to prove the usefulness of the M-cycle. The S phase fraction (SPF) calculated by the M-cycle was compared to that of bromodeoxyuridine labelling index (BLI) using colorectal carcinoma cell lines. The SPF value was slightly lower using the M-cycle than that of the BLI in Colo 201 and Colo 320 and lower significantly in Widr. This may indicate that the M-cycle effectively compensated for the background existing in the DNA histogram. The SPF value was computed both by the M-cycle and the sum of broadened rectangles model (SOBR). The SPF value of these cell lines showed a lower figure in the M-cycle than in the SOBR. The SPF value of paraffin-embedded material through the M-cycle and the SOBR was compared according to DNA ploidy patterns. The SPF value computed by the M-cycle was significantly lower in both ploidy patterns than that of the SOBR. In conclusion, the M-cycle is a useful tool for cell cycle analyses of simple DNA flow cytometric histograms obtained by paraffin-embedded material. PMID- 8203922 TI - [DNA content analysis and detection of c-myc and p53 products using flow cytometry in resected lung cancer cases]. AB - We quantitatively analyzed the c-myc and p53 products using flow cytometry in 28 cases of resected lung cancer and one case each of chorio-carcinoma, plasmacytoma, malignant mesothelioma and sclerosing hemangioma. In the lung cancer cases, c-myc and p53 products were detected in 10 cases (35%) and 7 cases (21%), respectively. These rates are higher than the DNA abnormal expression rates of the c-myc and p53 genes (15% and 12%, respectively) in our own data. In the adenocarcinoma of lung cancer cases, c-myc and p53 products were detected in 9 cases (53%) and 5 cases (29%), respectively. Among the squamous cell carcinoma cases, there were one case (11%) of c-myc expression and one case (11%) of p53 expression. DNA content analysis of the lung cancer patients revealed 7 cases of DNA diploidy and 21 cases of DNA aneuploidy. All 10 c-myc-positive cases showed DNA aneuploidy; thus the positive rate for c-myc products in the DNA aneuploidy cases was significantly different compared with the DNA diploidy cases (p < 0.05). In the sclerosing hemangioma case, we detected both c-myc and p53 products. Sclerosing hemangioma has been thought to be a benign tumor, but it may be a malignant tumor. PMID- 8203923 TI - [TS inhibition rate and flow cytometric analysis of DNA content in preoperative chemotherapy with biochemical modulator]. AB - Investigation of the TS (Thymidylate Synthetase) inhibition rate and flow cytometric studies of DNA content were conducted in 20 patients with human colorectal cancer who had undergone preoperative chemotherapy. Preoperative regimens of HCFU 240 mg/m2/day, given by 14-day oral dosage or HCFU 240 mg/m2/day and DP (Dipyridamole) 300 mg/body/day, both 14-day oral dosage were used. In 10 patients undergoing preoperative treatment with only HCFU and 10 patients with preoperative treatment of HCFU and DP, the free and total TS activities were measured with the tumor tissue and intact mucosa obtained from surgically resected tissues. With the TS activity, the TS inhibition rate (TSIR) was calculated from the free and total TS activities. Flow cytometric analysis of DNA content was measured before and after operation, and the difference was investigated. The changes of DNA histogram were found postoperatively in 2/10 (20%) patients with the HCFU dosage, and in 4/10 (40%) with the HCFU+DP dosage. TSIR exceeded 50% in all of these patients. The TSIR with DP (average, 64.5%) was higher than that of without DP (average, 57.5%) among them. Histological changes were found in 6/20 (30%) patients with preoperative chemotherapy. In all patients with preoperative chemotherapy, TSIR with DP (average, 63%) was higher than that without DP (average, 33%), but TSIR of normal tissue (average, 25%) was lower than that of these tumor tissues. These results showed that the benefit of this chemotherapy, including the change of DNA histogram, was especially higher when the TSIR of tumor tissue was high, and the TSIR with DP was also high. PMID- 8203924 TI - [Heterogeneity in gastric carcinoma with special reference to DNA content and mitotic activity: histopathologic differentiation]. AB - DNA ploidy was microspectrophotometrically investigated in 46 patients with gastric carcinoma. Measurements of DNA content and mitotic index (MI) were examined in the mucosal, submucosal, muscularis propria, and serosal layers of tumors, respectively. The frequency of cells with values exceeding hexaploid chromosome (6c) and mitotic counting analysis revealed a significantly higher value in the serosa than in the mucosa. This tendency was not evident in differentiated type adenocarcinoma but was noted in those with the undifferentiated type. There were 37 tumors (80.0%) with the same DNA distribution pattern in every layer of the stomach (homogeneous DNA ploidy). Heterogeneity of DNA ploidy was observed in nine tumors (20.0%). Carcinoma with heterogeneous DNA ploidy manifested a significantly higher incidence of metastasis to lymph nodes than did those with the homogeneous type. Characteristically, there was venous permeation preponderance in the differentiated type and peritoneal dissemination preponderance in the undifferentiated type. This evidence of DNA heterogeneity in gastric carcinoma tissue suggests a possible correlation with metastatic behavior. PMID- 8203925 TI - [A study of DNA heterogeneity on gastric cancer with serosal invasive exposure]. AB - In order to assess clinical significance, the DNA content in gastric cancer with serosal invasive exposure from 50 patients was determined by flow cytometry. The DNA histograms could be measured in two different vertical portions, on the mucosal and serosal sides. DNA heterogeneity was found in 15 patients (30.0%). These cases were divided into 4 groups according to the combination of DNA ploidy patterns. There were no significant differences in clinicopathological characteristics or survival rate between these 4 subgroups. Furthermore, the serosal invasion index (SII) defined as the ratio of serosal extent to mucosal extent was examined to determine the malignancy potential. All cases were divided into 2 groups, high SII and low SII, according to the value of SII. The survival rate was significantly lower in the high SII-aneuploid group compared with the low SII-diploid group. These results suggested that DNA analysis, subclassified by the serosal invasion index, is useful for assessment of the patient's prognosis. PMID- 8203926 TI - [Comparison of DNA index using flow cytometry between primary tumor and its metastatic regional lymph node in human gastric carcinoma]. AB - Flow cytometric determination of DNA ploidy was performed on paraffin-embedded specimens of primary tumor (Group A) and its metastatic lymph nodes (Group B) in 30 surgically resected cases, and the DNA index (DI) was compared between these two groups. In 25 of 30 cases (83.3%), all DI observed in Group B were also found in Group A; and in the remaining 5 cases, a series of DI not found in Group A were observed in group B. They were all poorly differentiated adenocarcinomas, 4 of which exhibited serosal invasion and prominent lymphatic permeation in their wall. In 28 cases (93.3%), the modal DI value in the primary tumor was also found in their corresponding metastatic lymph node, the frequency of which revealed a statistically significant difference from 18 cases (60%) in terms of median DI value, and from 10 cases (33.3%) in terms of maximum DI value (p < 0.01). It was suggested that the modal DI value in the primary tumor could signify an important clone relating to lymph node metastasis. No significant DI difference was observed in comparison of a series of DI seen in n1(+) and n2(+) group of metastatic regional lymph nodes. PMID- 8203927 TI - [Clinical significance of DNA ploidy heterogeneity in early gastric cancers]. AB - To evaluate the clinical significance of DNA ploidy heterogeneity (DH), four or more fresh tissue specimens were obtained from a tumor in 68 resected early gastric cancers. DNA content was measured by flow cytometry and the presence of DH was prospectively investigated. The incidence of DH correlated to invasion depth (m < sm), lymph vessel invasion (negative < positive) and tumor size (10 mm or less in diameter < more than 10). When the criteria of indication for minimum surgery were determined as the intramucosal cancer without n, ly and v factor, 85% of contraindication cases demonstrated DH. These results indicate that DH is a useful marker of tumor progression in early gastric cancer and will be an aid for determining indications for minimum resection. PMID- 8203928 TI - [DNA heterogeneity and its significance in colon carcinoma]. AB - We performed DNA flow cytometry analysis of colon carcinomas from the viewpoint of DNA heterogeneity. The materials were 25 colon carcinomas and 17 metastatic lymph nodes. Four different regions were examined in each primary tumor. The DNA index (DI) was classified into four groups. We classified the primary tumors into homogeneous and heterogeneous group according to the DI of the four regions of each case. Ten of 25 (40%) were classified as homogeneous and 15 (60%) as heterogeneous. The heterogeneous group tended to show more aggressive clinicopathologic characteristics. The corresponding rate between the maximum DI in the primary tumor and the DI in the metastatic lymph node was 65% (11/17). The maximum DI of the primary tumors was mostly seen in the metastatic lymph nodes, suggesting high metastatic potentiality of the higher DI clones. The examination of DNA heterogeneity may be useful for detecting the more precise character of the colon carcinomas. In heterogeneous cases, the higher corresponding rate of DI between primary and metastatic lesions suggested that metastasis occurred frequently in primary lesions containing gathering larger DI cells. PMID- 8203929 TI - [Clinical significance of flow cytometric DNA analysis in metastatic lymph node of colorectal cancer]. AB - Significance of flow cytometric DNA analysis in metastatic lymph nodes for assessing malignant potential of colorectal cancer was investigated using paraffin-embedded materials of primary lesions and metastatic lymph nodes from 65 patients who had been treated between 1975 and 1990. The DNA ploidy patterns of metastatic nodes were identical in 61.5% with those of primary lesions. Diploid cancers were significantly more frequent in metastatic nodes than in primary lesions. There were significantly more aneuploid cancers in proximal nodes than in distant nodes. There was no relation between ploidy patterns in primary lesions and survival. However, a significant relation was found between ploidy patterns in metastatic nodes and survival. Diploid cancer in metastatic nodes had a significantly better survival than aneuploid cancer, in all patients as well as those with curative resection. In patients with stage III and in those with the same depth of invasion, the survival rate of diploid cancer in metastatic nodes was significantly higher. There was no correlation between ploidy patterns in metastatic nodes and clinicopathological variables in primary lesions, such as histological type, depth of invasion, nodal involvement, peritoneal or hepatic involvement and stage. These results suggest that nuclear DNA content in metastatic lymph nodes may be a prognostic indicator in colorectal cancer with nodal involvement. PMID- 8203930 TI - [Study on relationship between intratumoral DNA heterogeneity and clinicopathological findings in colorectal cancer]. AB - We studied the relationship between intratumoral DNA heterogeneity and clinicopathological findings in 85 colorectal cancers. DNA ploidy was analyzed in 5 specimens from different sites of each tumor. When the difference in the DNA index (D.I) between several peaks in the same tumor was more than 0.1, the tumor was considered to consist of heterogeneous subpopulations with different DNA clones. DNA heterogeneity was found in 34 cases (40.0%). There was no relationship between DNA heterogeneity and depth of tumor invasion, lymph node metastasis or stage. The incidence of heterogeneity was significantly higher in the tumor with lower differentiation, liver metastasis or vessel invasion. PMID- 8203931 TI - [Research on the correlation between DNA recombinational mutation and cancer malignancy in human colon cancers]. AB - The mutagenicity of quercetin, a flavonoid, was examined by means of DNA fingerprint analysis using the Pc-1 and Pc-2 minisatellite probes that efficiently detect mutations due to recombination. Treatment of FM3A and BMT-11 tumor cells with 55 microM quercetin resulted in gain and loss of bands in the fingerprints in both cell lines. The frequencies of the clones having undergone mutation were 9/26 and 2/11, using Pc-1 probe, respectively, in the two lines. These results seem to provide a molecular basis for the phenotypic variations of BMT-11 tumor cells induced by quercetin, giving direct evidence of genetic instability of the tumor cells. Moreover, we examined for a possible correlation between frequencies of DNA recombinational mutations and cancer malignancy in human colon cancers. DNA of four human colon cancer tissues and corresponding peripheral blood cells were prepared, respectively, and examined by DNA fingerprint analysis using hPc-1 polymorphic minisatellite probe. These four specimens exhibited no extra-bands resulting from recombination and/or DNA slippage at present. We would explain how the prognosis of cancer patients is related to frequencies of DNA recombinational mutation. PMID- 8203933 TI - [Flow cytometric analysis of DNA ploidy in intramucosal gastric carcinoma]. AB - In order to investigate whether or not DNA ploidy was altered in intramucosal gastric carcinomas, nuclear DNA content of biopsy specimen was measured using flow cytometry in 38 intramucosal carcinomas. DNA aneuploidy was detected in 27 of 38 lesions (71.1%), and noted more frequently in differentiated carcinomas than in undifferentiated ones (83.0% vs. 20.0%, p < 0.01). There was no significant relationship between the frequency of DNA aneuploidy and macroscopical type or tumor size. DNA aneuploidy was even found in two of three minute carcinomas (5 mm or less in diameter). DNA indices showed 1.2 or lower values in 40% of the lesions with DNA aneuploidy. The average value of DNA index was significantly larger in depressed type than in elevated type (p < 0.01). In conclusion, DNA ploidy is altered in most differentiated intramucosal carcinomas. A high resolution method is essential for accurate determination of DNA ploidy in intramucosal carcinomas, especially elevated ones. PMID- 8203932 TI - [DNA heterogeneity in oral cavity and hypopharyngeal carcinoma]. AB - The study was carried out on 18 cases of oral cavity carcinoma and 12 cases of hypopharyngeal carcinoma to assess the degree of intratumoral heterogeneity and the relation to tumor size, lymph metastasis and histological type. In oral cavity carcinoma, 6 cases (33%) were aneuploid, while in hypopharyngeal carcinoma all were aneuploid. DNA heterogeneity was identified in 4 cases (22%) in oral cavity carcinoma, end in 6 cases (50%) of hypopharyngeal carcinoma. No correlation was found between DNA heterogeneity and tumor size, lymph metastasis and histological type. However, even early carcinomas have intratumoral DNA heterogeneity. It was supposed that the result which hypopharyngeal carcinoma had higher degree of aneuploid and DNA heterogeneity comparing with oral cavity carcinoma supported that hypopharyngeal carcinoma had higher clinical malignancy from the aspect of proliferative movement. The data indicate that it is impossible to analyze correct DNA content by only one specimen and it is important to investigate intratumoral DNA heterogeneity to research the mechanism of multiplicity and clinical malignancy of carcinoma. PMID- 8203934 TI - [Relation between nuclear DNA content and lymph node metastasis in submucosal early gastric cancer]. AB - To investigate a possible relation between the nuclear DNA content and lymph node metastasis of submucosal early gastric cancer, DNA content was analyzed for 46 patients with lymph node metastasis and 67 patients without nodal metastasis. DNA aneuploidy was found in 20 (43.5%) of 46 patients with lymph node metastasis and in 31 (46.3%) of 67 patients without it. There was no statistical difference in the incidence of aneuploidy between the 2 groups. Among the cases with DNA diploidy, the mean value of S phase fraction was 6.82% in patients with lymph node metastasis and 5.65% in those without metastasis. The mean value of S phase fraction was significantly higher in patients with nodal involvement (p < 0.05). Furthermore, among the cases with DNA aneuploidy, the mean value of G2/M phase fraction was 11.03% in patients with lymph node metastasis and 7.54% in patients without metastasis. The mean value of G2/M phase fraction was significantly higher in patients with nodal involvement (p < 0.05). These findings suggest the significant value of the S and G2/M phase fraction for the prediction of lymph node metastasis in patients with submucosal early gastric cancer. PMID- 8203935 TI - [Flow cytometric DNA analysis of colorectal carcinoma in adenoma]. AB - We evaluated the DNA ploidy in 23 lesions of colorectal carcinoma in adenoma (CIA) and 90 adenomas without carcinomas by flow cytometry using fresh samples. DNA ploidy of carcinoma and adenoma components were assessed, respectively, with 17 paraffin-embedded samples of CIAs. The incidence of DNA aneuploidy (AP) was significantly higher in CIAs than in adenomas (47.8% vs. 12.2%, p < 0.01). Even in adenoma components of CIAs, AP tended to be found more frequent than in adenomas (41.2% vs. 12.2%). The incidence of AP in adenoma components was similar to that in carcinoma components (35.3%) in CIAs. In conclusion, DNA aneuploidy in adenomas may be a marker of malignant potential. PMID- 8203936 TI - [Detection of chromosomal numerical aberration in early colorectal carcinomas using fluorescence in situ hybridization]. AB - The authors have performed fluorescence in situ hybridization (FISH) in tissue sections of archival paraffin-embedded blocks of seven cases in adenoma and ten cases in carcinoma in order to clarify which chromosomal aberration occurred in association with multi-step carcinogenesis in colorectal carcinomas, using alpha satellite DNA probes to chromosome 11 and 17, D11Z1 and D17Z1, respectively. Monosomy of chromosome 11 was most frequented (5/7, 71.4%) in adenoma, and trisomy of chromosome 17 was predominant (9/10, 90.0%) in carcinoma. The numerical chromosomal aberrations can be already detected at the stage of adenoma, and monosomy of chromosome 11 was mainly observed in adenoma. Furthermore, malignant transformation arising from adenoma accounted for most of the trisomic change in chromosome 17. Consequently, applying the FISH technique to tissue sections from archival paraffin embedded specimen, it would be possible to distinguish between the cancerous and non-cancerous regions in view of chromosomal numerical aberrations. The authors emphasized that intratumoral heterogeneity could be elucidated at the chromosomal level. PMID- 8203937 TI - [Feasibility of DNA analysis for prognostic evaluations of colorectal cancer using touch preparations and image cytometry]. AB - The purpose of this study is to demonstrate the applicability of DNA ploidy analysis by using touch preparations obtained from fresh and frozen tissues on the prognostic evaluations of colorectal cancer, especially the development of hepatic metastases. The specimens obtained from surgically resected colorectal carcinomas (32), and hepatic metastases (4), were lightly touched with the slide glasses. Among the 32 patients with colorectal cancers, 7 had synchronous liver metastases, and 5 metastases developed metachronously. After formalin-fixation and Feulgen staining, the DNA analysis was performed by image cytometer (ICM, CAS200R). The data were expressed as the ploidy patterns and DNA indices (p-DNAI: peak DNA index, m-DNAI: mean DNA index), and were correlated very well with those obtained from cytophotometry. The DNA ploidy pattern among the 32 colorectal cancer specimens were Aneuploid(A) in 16, Polyploid (P) in 7, Diploid (D) in 4 and D+P in 5. The cases with synchronous or metachronous liver metastases had a higher m-DNAI (1.74 +/- 0.28) and were Aneuploid in 8, P in 3, and D+P in 1 case. Aneuploidy or Polyploidy predominated among the cases with metachronous liver metastases (4 in 5 cases), with m-DNAI higher than 1.5. Thus, "m-DNA > 1.5" could be a useful prognostic indicator of the high risk group of liver metastases. The liver metastases specimens had Aneuploid and Polyploid patterns in 2 cases each, with m-DNAI ranging from 1.88 to 2.31. DNA ploidy pattern analysis using touch preparations with image cytometry may be useful in determining the prognosis for colorectal cancer. PMID- 8203938 TI - The mental status of health care reform. PMID- 8203939 TI - A nurse-managed inpatient program for patients with chronic mental disorders. AB - The deinstitutionalization movement has left a legacy of need for appropriate care for inpatients with chronic refractory mental illness. This article describes a nurse managed program for such patients based on the principles of a therapeutic milieu. The program was formally defined for a 6-month period with an effort to include outcome measures for program evaluation. Multidisciplinary treatment team planning with a psychiatric nursing clinical specialist as team leader provided a format for putting therapeutic concepts into practice. The nurse clinical specialist and two nurse practitioners served as case managers as well as primary care providers. Program evaluation showed that cost-effective quality care could be achieved with a reduction in polypharmacy and overall neuroleptic usage. The notion of a restraint appropriate environment, with the goal of minimizing restraint use, was introduced and put into practice. PMID- 8203940 TI - Movement therapy with depressed inpatients: a randomized multiple single case design. AB - The relative lack of research on movement therapy in inpatient versus outpatient settings stems from the difficulty of conducting an interpretable study in clinical situations where multiple treatments exist. To control for the multiple treatment confound, this study used a randomized single-case experimental design with 12 replications. Results indicated that the movement therapy, which was designed to target the syndrome of a major depressive episode had a positive effect on mood across experiments (p < .001). From a clinical perspective, these results support the use of a movement program as adjunctive treatment, and challenge the view that movement is recreation but not therapy. PMID- 8203941 TI - The private psychiatric hospital scandal: a critical social approach. AB - The recent events that transpired in the for-profit psychiatric hospital industry in which hospitals were alleged to engage in practices which ranged from unethical to illegal underscore the importance of examining the contexts of nursing practice. A wide range of environmental factors and unchallenged assumptions may influence the care of clients and may become obstacles to effective and ethical nursing practice. Critical social theory offers nursing a potentially valuable tool from which to illuminate and examine otherwise unexamined aspects of the environment. PMID- 8203942 TI - A nontraditional approach to family violence. AB - Family violence has often been conceptualized as a linear phenomenon in which perpetrators commit acts intended to hurt victims. Intervention in these circumstances involves treating the perpetrator and the victim individually. In contrast, this article presents a Systemic Belief Approach to the situation of mutual family violence. A case example illustrates the influence of beliefs on the occurrence of violent acts between family members (in this case, sole-parent mother and adolescent daughter). Family systems nursing interventions such as reflective questions and reflecting teams are used to challenge the family's constraining beliefs, which enables the coevolution of facilitative beliefs that invite healing. PMID- 8203943 TI - Critical incident stress debriefing: a family nursing intervention. AB - Critical Incident Stress Debriefing is an intervention that assists patients and families to master the stresses resulting from being a witness to or victim of violent acts. Intervening at the level of the family system, the clinical nurse specialist can facilitate communication, decrease anxiety, and provide education regarding the post-trauma response. PMID- 8203944 TI - Systematic clinical supervision in a child psychiatric ward: satisfaction with nursing care, tedium, burnout, and the nurses' own report on the effects of it. AB - The effects of systematic clinical supervision on all nurses (n = 11) at a ward for child psychiatric care was evaluated by means of open-ended questions, the tedium measure, Maslach's burnout inventory (MBI), and the satisfaction with nursing care at baseline, and after 6 and 12 months of supervision. Two main themes emerged: (1) being understood and understanding others led to improved cooperation and self-confidence and, (2) broadened and better knowledge base led to increased goal-oriented and active nursing actions in their clinical work. The nurses' satisfaction increased significantly regarding responsibility, organization, quality of care, cooperation, and comfort in the work group. The degree of tedium decreased significantly regarding mental exhaustion, whereas there were no significant changes in the degree of burnout as measured by MBI. The data point to the fact that systematic clinical supervision may be a way to show and use the knowledge embedded in practice and to improve the efficiency, the climate, and the cooperation of a work group. PMID- 8203945 TI - Psychological distress in family members living with human immunodeficiency virus/acquired immune deficiency syndrome. AB - This article describes the psychological distress experienced by family members living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). Survey data were collected from 133 individuals, (47 parents, 53 siblings, 33 adult family members who have HIV/AIDS) representing 80 families. In depth interview and observational data were collected from a subset of the sample. The physical and psychological health of individual family members was assessed by the 53-item Brief Symptom Inventory. Parents, siblings, and people living with AIDS (PWAs) reported higher levels of overall distress and scored higher on symptom dimensions and clinically discrete symptoms than normative comparison groups. Implications of these findings for research, clinical practice, and health and social service policy are identified and discussed. PMID- 8203946 TI - Private insurance coverage for the treatment of mental illness versus general medical care: a policy of inequity. AB - Private insurance coverage has historically been and continues to be discriminatory toward patients requiring treatment for mental illness and substance abuse disorders in comparison with those in need of general medical care. Factors contributing to this disparity include stigma, relatively low overt consumer demand for psychiatric care, lack of knowledge about psychiatric illness and treatment on the part of insurers, a historical reliance on public sector psychiatry, and the assumption that more liberal psychiatric benefits result in unnecessary and excessive use. Strategies aimed at eliminating discriminatory insurance practices against those in need of mental health care must be implemented. Recommended approaches include further research on the cost effectiveness of mental health care, public education regarding the nature of mental illness and its treatment, patient/family advocacy, and the marketing of services by mental health professionals. PMID- 8203947 TI - Specialist training in rheumatology--the need for a curriculum and assessment. PMID- 8203948 TI - Defining osteoarthritis of the hand for epidemiological studies: the Chingford Study. AB - OBJECTIVES: To explore the relative merits of clinical and radiological examination in defining hand osteoarthritis (OA) for epidemiological purposes. METHODS: A total of 976 women aged 45-64 years were selected from the general population and underwent a structured interview, clinical examination of the hand joints and radiography of the hands and knees. The inter-relationship of the clinical and radiological findings was examined, and also the association of each with hand symptoms and the presence of knee OA. RESULTS: Clinical and radiographic signs of hand OA generally correlated with each other, and each was associated with hand symptoms to a similar degree. When analysed in combination, they were only marginally better at predicting symptoms than when tested individually. However, when they were examined in relation to radiographic features of knee OA, there was a significantly stronger association with radiographic features of hand OA than with clinical features. CONCLUSIONS: Hand radiology provides a better overall assessment of osteoarthritis than physical examination of the interphalangeal joints or carpo-metacarpal joint; in situations where radiology is not available clinical examination is a viable substitute. PMID- 8203949 TI - Infection rate and use of antibiotics in patients with rheumatoid arthritis treated with methotrexate. AB - OBJECTIVE: To investigate prospectively the frequency and type of infections and the use of antibiotics among patients with rheumatoid arthritis (RA) on methotrexate (MTX) and patients with RA without MTX. METHODS: Every three months for one year 77 patients on MTX and 151 patients without MTX were asked about infections and the use of antibiotics by means of a standardised questionnaire. Medication was checked with the pharmacist. RESULTS: In the MTX group there were significantly more infections and more antibiotic therapy. The relative risks for patients on MTX of infection or antibiotics use were 1.52 (95% Confidence Interval (CI) 1.04-2.22) and 1.49 (95% CI 1.04-2.13), respectively. The relative risk of MTX for respiratory tract infections was 1.43 (95% CI 0.96-2.14) and for skin infections 2.19 (95% CI 1.45-3.31). The increased risks could only partly be explained by differences in disease severity and were not related to either duration of MTX therapy or use of prednisone. Three patients in the MTX group had herpes zoster versus one in the control group. CONCLUSIONS: Treatment with MTX increases the rate of infection and thus the use of antibiotics but does not lead to serious complications necessitating discontinuation of the drug. PMID- 8203950 TI - Humoral immune response against minor collagens type IX and XI in patients with cartilage graft resorption after reconstructive surgery. AB - OBJECTIVES: The humoral immune response against a broad spectrum of cartilage antigens (cellular and matrix antigens) was studied in a group of patients who showed resorption and/or rejection of transplanted cartilage in nasal surgery. METHODS: Sera were obtained from patients with successful and unsuccessful cartilage grafting in the nose, from age and sex-matched healthy donors and from patients with rheumatoid arthritis. Antibodies to cartilage components were analysed by the following methods: (1) indirect immunofluorescence on cartilage sections, (2) ELISA using cultured human chondrocytes, isolated chondrocyte membranes and purified collagens type I, II, III, VI, IX and XI, and (3) immunoblotting with purified collagens and chondrocyte cell membranes. RESULTS: In the cartilage grafting group showing resorption problems, levels of anti collagen antibodies were significantly higher against native collagen types IX (p < 0.002) and XI (p < 0.002) compared with the non-resorption group and the normal donors. Both transplantation groups revealed elevated reactivities against isolated chondrocytes in the ELISA. In contrast, no reactivity was detectable against collagens type II, III, and VI and chondrocyte cell membranes by both ELISA and immunoblotting. CONCLUSIONS: These data demonstrate for the first time the existence of a humoral immune response, primarily directed against the so called 'minor cartilage collagens', in patients showing cartilage resorption. Autoreactivities to collagen which are typical of inflammatory rheumatic diseases may also play an important role in the repeated failure of cartilage grafting. PMID- 8203952 TI - Effect of three animal models of inflammation on nerve fibres in the synovium. AB - OBJECTIVES: Both sensory and sympathetic nerve fibres are depleted in the synovium in rheumatoid arthritis (RA). The hypothesis that the induction of an inflammatory response in the synovium is capable of causing depletion of nerve fibres was tested. METHODS: To investigate this phenomenon experimental arthritis in the rat was induced by three different methods and the synovium was examined for evidence of nerve depletion by immunocytochemistry. RESULTS: In a synovitis induced by latex spheres, a mainly macrophage foreign body type reaction, no nerve depletion was seen. In contrast both in an antigen-induced and a hydrogen peroxide-induced model of arthritis nerve fibre depletion was observed. This appeared to affect sensory and sympathetic nerve fibres equally. Nerve fibre depletion was only seen in areas of inflammatory cell infiltration indicating that a mixed lymphocyte and macrophage population of cells may be necessary for this effect. CONCLUSIONS: An inflammatory response, containing lymphocytes and macrophages, in the synovium is capable of the depletion of the finely myelinated and unmyelinated neuropeptide-containing nerves. PMID- 8203951 TI - Changes in levels of soluble T-cell activation markers, sIL-2R, sCD4 and sCD8, in relation to disease exacerbations in patients with systemic lupus erythematosus: a prospective study. AB - OBJECTIVES: To assess serial activation of T-cell subsets in relation to auto antibody production and the occurrence of disease exacerbations in patients with systemic lupus erythematosus (SLE). METHODS: To study the possible role of T cells in the pathophysiology of the disease, 16 consecutive exacerbations were prospectively studied in a cohort of patients with SLE, and serial plasma levels of sIL-2R, sCD4, and sCD8 preceding and during these exacerbations were determined. Levels of these molecules were related to total IgM and IgG, and anti dsDNA. RESULTS: During major disease exacerbations (n = 6), levels of sIL-2R increased significantly (p < 0.001). Levels of sCD4 were predominantly in the normal range, whereas levels of sCD8 were frequently increased. No change in levels of both molecules could be detected in the period before the exacerbation. During minor exacerbations (n = 10), levels of sIL-2R remained stable. Levels of sCD4, however, tended to drop, whereas levels of sCD8 tended to rise. No correlations were found between sIL-2R, sCD4 or sCD8 on the one hand, and total IgM, IgG, or anti-dsDNA on the other. CONCLUSIONS: Levels of sIL-2R are increased, and rise before major exacerbations of SLE. Levels of sCD4 and sCD8, however, are not related to levels of sIL-2R, and do not reflect B-cell activation, nor disease activity during exacerbations of SLE. Thus for the clinical follow up of SLE measurement of levels of sCD4 or sCD8 is of limited value. PMID- 8203953 TI - Calcitonin inhibits production of immunoglobulins, rheumatoid factor and interleukin-1 by mononuclear cells from patients with rheumatoid arthritis. AB - OBJECTIVES: Elcatonin (eCT), an eel calcitonin derivative, is shown to considerably improve the clinical signs and symptoms, as well as laboratory data, in patients with rheumatoid arthritis (RA). The therapeutic efficacy of eCT, however, is reduced by preceding and/or concomitant use of corticosteroid. Thus the effects of eCT on the production of immunoglobulins, IgMRF and interleukin-1 (IL-1) by mononuclear cells (MNCs)/monocytes were studied, and compared among patients with RA that received three kinds of treatment and also normal volunteers (NV). METHODS: Ten patients with RA had been treated with a non steroidal anti-inflammatory drug only (NSAID group), 11 with oral prednisolone (PSL group), and eight with intramuscular eCT (eCT group). MNCs/monocytes from these patients, and also 10 from the NV group, were collected and cultured. IgG, IgA, IgM, IgMRF, IL-1 alpha and IL-1 beta in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). In the NSAID, PSL and NV groups, eCT was added to the culture medium, and the effects of eCT on production of these substances were studied. RESULTS: Baseline production of IgM, IL-1 alpha and IL-1 beta by MNCs/monocytes in the eCT and NV groups was significantly lower than that in the NSAID group. Furthermore, addition of eCT to the culture medium significantly inhibited the productions of IgG, IgMRF, IL-1 alpha and IL-1 beta by MNCs/monocytes in the NSAID group, whereas production of neither IgG, IgA, IgM, IgMRF nor IL-1 by MNCs/monocytes in the PSL and NV groups was affected by eCT. CONCLUSION: eCT may regulate immune responses through MNC/monocyte function in patients with RA. The present results support our proposal that eCT is an effective agent for the treatment of RA. PMID- 8203954 TI - The effects of Tenidap on cytokine induced proliferation of human synovial fibroblasts in vitro. AB - OBJECTIVES: Tenidap, a new anti-rheumatic agent, is a lipoxygenase and cyclooxygenase inhibitor, and is reported to inhibit the production and action of interleukin 1 (IL-1). Since eicosanoids, IL-1, and other cytokines may influence the growth of fibroblasts in the joint synovium the study was carried out to determine the effects of Tenidap on cytokine induced proliferation of these cells in vitro. METHODS: Cell cultures derived from patients with a variety of rheumatic diseases were cultured in different concentrations of Tenidap sodium, with or without IL-1, tumour necrosis factor alpha (TNF), IL-6, basic fibroblast growth factor (bFGF), or transforming growth factor beta (TGF beta). Cell proliferation was measured using a crystal violet colourimetric assay. Prostaglandin E2 levels in culture supernatants were measured by radioimmunoassay. RESULTS: Tenidap at concentrations above 10 micrograms/ml inhibited cell growth, while at 1.25-5 micrograms/ml there was a small but significant increase in proliferation compared with controls. A further increase in growth was obtained when cells were incubated with Tenidap+IL-1, TNF or bFGF, and this was significantly higher than in the presence of any cytokine alone. Stimulation of IL-1 induced growth by Tenidap was reduced by addition of high levels of exogenous PGE2 (100 ng/ml) although growth was still higher than in IL 1 alone. CONCLUSIONS: Depending on concentration, Tenidap may inhibit or stimulate synovial fibroblast growth. Our results suggest that augmentation of growth by low concentrations cannot be explained by inhibition of PGE2 production alone. Tenidap may directly stimulate cell growth or may block other fibroblast factors which are involved in control of cytokine induced proliferation. PMID- 8203955 TI - A western blot approach to detection of human plasma protein conjugates derived from D-penicillamine. AB - OBJECTIVES: To develop and apply an immunochemical approach to the study of drug plasma protein conjugates derived from the anti-arthritic drug D-penicillamine (DP). METHODS: An antiserum with specificity for protein-conjugated DP was raised in a rabbit. Plasma samples from patients receiving DP or from incubations of isolated normal plasma with DP were analysed for DP-derived conjugates by Western blotting using the anti-drug antibody. RESULTS: A single DP-positive protein band was detected in plasma samples from 15/16 patients with rheumatoid arthritis receiving DP but in none of 20 patients of similar disease status who had not taken DP. The positive band appeared in patients' plasma during the course of treatment with DP. It was seen under nonreducing but not reducing conditions indicating that the drug is disulphide linked to the protein. The drug-modified protein migrated to a position intermediate between the trailing edge of albumin and the leading edge of transferrin (both non-reduced) suggesting a molecular weight of between 66 and 77 kDa. Incubations of normal human plasma, but not purified albumin or transferrin, with low concentrations of DP generated the same distinct band plus several less intense DP-positive bands. CONCLUSIONS: Drug plasma protein conjugates derived from DP in vivo and in vitro can be detected immunochemically by the Western blot method. Theories of DP immunotoxicity have implicated antigenicity of the drug, but this is the first immunochemical demonstration of a potential DP-derived antigen in human plasma. The method we describe may have application to studies of the relationship between DP antigenicity and toxicity. PMID- 8203956 TI - Increased frequency of TAP2B in early onset pauciarticular juvenile chronic arthritis. AB - OBJECTIVES: To determine whether polymorphisms of the TAP genes, which lie within the major histocompatibility complex (MHC), are associated with juvenile chronic arthritis (JCA). METHODS: Eighty five JCA patients and 166 white controls were typed for the TAP gene alleles using ARMS-PCR. The same populations were analysed for DRB1 and DPB1 alleles using PCR-SSO typing. RESULTS: TAP2B was increased in early onset pauciarticular JCA (EOPA-JCA) compared with controls (62% v 44% Odds ratio (OR) 2.1, 95% CI 0.9-4.7). After allowing for the known linkage disequilibrium between TAP2B and DR1 the association of TAP2B and EOPA-JCA was maintained (OR 3.5, 95% CI 1.3-9.7). HLA-DRB1*04 and TAP2D were found to be in linkage disequilibrium in both the control (delta 0.018 p < 0.05) and JCA patient groups (delta 0.021 p < 0.05). No linkage disequilibrium was found between the TAP and DPB1 alleles. CONCLUSIONS: The association between TAP2B and EOPA-JCA is a further indication of the heterogeneity which exists in this clinically defined subgroup of patients. PMID- 8203957 TI - Antibodies to endothelial cells in Behcet's disease: cell-binding heterogeneity and association with clinical activity. AB - OBJECTIVES: To investigate the prevalence and characteristics of antibodies to endothelial cells (aEC) from large vessel and from microvasculature in a group of patients with Behcet's disease (BD) to determine the relationship of these antibodies with clinical and laboratory features of the disease. METHODS: Thirty patients with BD were prospectively and consecutively studied. The aEC were determined by enzyme-linked immunosorbent assay (ELISA) using endothelial cells derived from human umbilical vein (large vessel) as well as from retroperitoneal adipose tissue (microvasculature). RESULTS: Fifteen patients (50%) had aEC, either directed to large vessel [8(26%) patients] or microvascular [13(43%) patients] endothelial cells. The percentage of active patients was significantly higher in the aEC-positive group [12(80%) patients] compared with the aEC negative group [5(33%) patients] (p < 0.05). CONCLUSIONS: Patients with BD have a high prevalence of aEC when microvascular endothelial cells are used in the assay. These antibodies seem to be a marker of disease activity in this condition, previously considered as negative for autoantibodies. PMID- 8203958 TI - Quantitative radiography of osteoarthritis. PMID- 8203959 TI - Hajdu-Cheney syndrome. PMID- 8203961 TI - Eosinophilic fasciitis in a father and son. PMID- 8203960 TI - Recurrent infections, pericarditis and renal disease in a patient with total C2 deficiency and decreased NK cell function consistent with acute rheumatic fever and systemic lupus erythematosus. PMID- 8203962 TI - Massive eosinophilic synovitis and reactive arthritis associated with filarial infection. PMID- 8203963 TI - Antiperinuclear and anti-RA33 antibodies in juvenile chronic arthritis. PMID- 8203964 TI - Circulating T cell subtypes in polymyalgia rheumatica and giant cell arteritis: variation in the percentage of CD8+ cells with prednisolone treatment. PMID- 8203965 TI - Microcirculation in ankylosing spondylitis. PMID- 8203966 TI - Cervical neuropathology in rheumatoid arthritis. PMID- 8203967 TI - Fibromyalgia in the workplace. PMID- 8203968 TI - Recurrent thyroid cancer. Role of surgery versus radioactive iodine (I131) AB - OBJECTIVE: This retrospective study compared treatment and survival of patients with recurrent well-differentiated thyroid cancer that was diagnosed exclusively by I131 scanning, or by clinical examination. SUMMARY BACKGROUND DATA: Despite the usual excellent prognosis of differentiated thyroid cancer, approximately half of patients who developed a recurrence eventually succumb to the disease. It has been speculated, but not proven, that recurrent disease detected solely by I131 scanning may offer a better prognosis than recurrences detected clinically and be amendable to I131 ablative therapy without the addition of surgical resection. METHODS: Seventy-four cases of recurrent differentiated thyroid cancer were identified retrospectively and examined regarding the location of recurrence, mode of detection of recurrent disease, treatment of recurrence, and outcome of patients. Using Fischer exact testing, outcome results for recurrences detected exclusively by I131 scan was compared to that of clinically diagnosed recurrences; among clinically detected recurrent cases, treatment with surgery only was compared to surgery/I131 ablation. Kaplan-Meier actuarial survival curves were generated for clinically detected recurrent cancer treated by surgery only and compared to those treated by surgery and I131 ablation using Gehan Wilcoxon and log-rank analysis. RESULTS: Recurrences located most commonly were regional (53%), followed by local (28%), distant metastasis (13%), and combined locoregional (6%). Among patients whose recurrence was detected scintigraphically, only 9.5% had persistence of disease or were dead of disease compared to 54.0% of patients with clinically detected recurrences. Radioactive iodine ablation in scintigraphically detected recurrences salvaged 18 of 20 patients (90%). Among clinically detected recurrences, surgery alone salvaged 12 of 21 patients (57%), whereas the addition of I131 ablation to surgery salvaged only 3 of 15 patients (20% p = 0.05). CONCLUSION: The probability of dying or living with persistent disease after treatment of recurrent thyroid cancer is less for I131 detected recurrences compared to clinically diagnosed recurrences; I131 ablation without surgery constitutes adequate therapy for scintigraphically detected recurrences. In clinically recurrent disease, the addition of I131 ablation to curative resection does not appear to improve survival. PMID- 8203969 TI - Interferon-alpha-2a for the treatment of complex hemangiomas of infancy and childhood. AB - OBJECTIVE: The authors describe the use of interferon-alpha-2a (IFN-alpha-2a) in the treatment of complex hemangiomas and review the role of interferon (IFN) in this example of an angiogenic disease. SUMMARY BACKGROUND DATA: Hemangiomas are the most frequent tumors of infants and children. They grow rapidly for 6 to 8 months and then resolve over a period of years. Approximately 5% produce life-, sight-, or limb-threatening complications, with mortality rates between 20% and 50%. Aggressive therapy with steroids, arterial ligation or embolization, or surgery has been used in these situations with variable results and high morbidity. Recently, IFN-alpha was found to be effective treatment in these complex hemangiomas. METHODS: Four infants and one child were treated with IFN alpha-2a at an initial subcutaneous dose of 1 million units/m2/day and a sustained dose of 3 million units/m2/day for 5 to 11 months. Appropriate laboratory values were monitored and adverse reactions and ultimate response to therapy were recorded. RESULTS: Two patients experienced minor complications that were managed easily. Three patients had total or near-total regression of the hemangioma, one had partial (50%) regression, and one had stabilization but no regression after an average of 7.1 months of IFN therapy. CONCLUSION: Interferon alpha inhibits angiogenesis and endothelial cell migration and proliferation in vitro. The patients in this study add to the growing number who have benefited from IFN therapy. As such, IFN-alpha should be considered as a first-line agent in treating complex hemangiomas of infants and children. PMID- 8203970 TI - Long-term complications of laparotomy in Hodgkin's disease. AB - OBJECTIVE: The authors determined the incidence of complications in 133 patients who had undergone staging laparotomy with splenectomy before treatment for Hodgkin's disease (stages I-IV). METHODS AND MATERIALS: Medical records were reviewed, and the patients or their relatives were interviewed. Median follow-up after laparotomy was 15.7 years (range = 2.5-28 years). RESULTS: Ten episodes of overwhelming postsplenectomy infection (OPSI) were documented in nine patients (6.8%). None of 25 patients who received pneumococcal vaccine before splenectomy developed OPSI. Patients with advanced (stages III-IV) or recurrent Hodgkin's disease were at higher risk of OPSI than those with early disease, and those who received combined modality oncologic therapy were at greater risk than those receiving less intensive treatment. Surgical complications included small bowel obstruction in 13 patients (9.8%), necessitating repeat laparotomy in 9 patients (6.8%), atelectasis in 17 patients, abscess in 3 patients, and 1 wound dehiscence. No deaths occurred as a result of surgical complications. Causes of death in the 29 patients who died included Hodgkin's disease (12 patients), acute treatment-related morbidity (1 patient), leukemia (5 patients), bone marrow failure (3 patients), solid malignancy (2 patients), intercurrent disease (4 patients), unknown causes (1 patient), and OPSI (1 patient). CONCLUSION: With presplenectomy pneumococcal vaccination and modern surgical techniques, the long term risks of laparotomy with splenectomy are acceptable if knowledge of the pathologic extent of abdominal Hodgkin's disease would alter treatment regimens. PMID- 8203971 TI - Nonoperative management of solid organ injuries in children. Is it safe? AB - OBJECTIVE: The authors reviewed their experience with life-threatening blunt injuries in approximately 2900 children (0-14 years) admitted to the designated state pediatric shock trauma unit between 1990 and 1993. METHODS: During this time, the authors treated all severely injured children with a prospective, nonoperative protocol if they were hemodynamically stable after less than 40 mL/kg fluid replacement, had proven evidence of solid organ injuries and remained stable in the pediatric intensive care unit under surgical management. RESULTS: Twenty-eight children had computed tomography (CT) or operatively proven lacerations of the spleen, 25 had lacerations of the liver, 18 had lacerations of the kidney, 7 had lacerations of the pancreas, and 11 had two or more solid organ injuries. Three of the 28 children with injured spleens required laparotomy (two splenectomy, one splenorrhaphy). Two of the 25 children with liver injuries required laparotomy (one suturing, one partial resection). One of the 18 children with kidney injuries required laparotomy (nephrectomy), and 3 of the 7 children with pancreas injuries required laparotomy (two resection, one pseudocyst). There were three deaths after laparotomy (two head, one chest/abdominal). There were no deaths in the children managed nonoperatively, and there were no immediate or long-range complications. CONCLUSIONS: Comparison of the authors' data with the National Pediatric Trauma Registry shows similar results. The authors believe that nonoperative management of solid organ injuries under careful surgical observation in a pediatric intensive care unit is safe and appropriate. PMID- 8203972 TI - Pneumonia in the surgical intensive care unit. Immunologic keys to the silent epidemic. AB - OBJECTIVE: The authors undertook a prospective study of trauma victims in the intensive care unit (ICU) to investigate the clinical course of pneumonia and the local and systemic immune responses to the pneumonia. SUMMARY BACKGROUND DATA: The silent epidemic of pneumonia has been an "unappreciated killer" in terms of being overlooked in surgical ICUs for the past 5 years, and specifically, the most common major infection after severe trauma. Little is known about the immune response to an acute pulmonary infection. METHODS: The authors studied 50 consecutive, critically ill trauma patients, with a mean injury severity score of 28 +/- 2, who developed pneumonia while ventilated mechanically. Patients were observed clinically, and specific immunologic parameters, including major histocompatibility antigen HLA-DR, complement receptor (CR3), and Fc receptor (FcRIII), were measured in circulating and local alveolar leukocytes for up to 30 days. Eleven patients provided unique clinical data via bronchoscopy for unilateral pneumonia, with collection of bronchoalveolar lavage (BAL) fluid from both the infected and uninfected sides. RESULTS: Patients developed clinical pneumonia 5.3 +/- 0.4 days after admission to the ICU. At diagnosis, mean temperature was 101.4 F, white blood cell count was 16,000/mm3, arterial oxygen tension was 104 +/- 14, fraction of inspired oxygen was 0.47, and positive end expiratory pressure was 5. Thirty patients (Group A) recovered relatively promptly; 20 patients had prolonged illnesses (Group B), 15 of whom ultimately survived, and five of whom died. Patients with poor outcomes had greater leukocytosis (p < 0.05) and temperature elevation (p < 0.05) after 5 days of pneumonia. Immunologically, peripheral leukocyte expression of HLA-DR, FcRIII, and CR3 was equivalent in both groups. However, the expression of all three antigens on local alveolar leukocytes was decreased to a greater extent in the poor outcome group compared to the good outcome group, evident before any clinical differentiation between the two outcome groups. CONCLUSIONS: Pneumonia prolonged duration of mechanical ventilation, ICU and hospital stay, and overall infectious morbidity. Although immune suppression has been recognized as a result of initial injury, the development of pneumonia coincided with the nadir of immune function. Poor outcome patients were clinically identifiable 5 days after pneumonia and immunologically identifiable within 2 days. Moreover, there was localized suppression of pulmonary leukocytes at the site of the infiltrate compared to the uninfected lobes. This same alteration was noted in experimental Klebsiella pneumoniae pneumonia. This evidence suggests that there is active immune participation within the respiratory system. It also suggests that there are predispositions to pulmonary infections, and it may allow immune modulation targeted to pulmonary leukocytes to hasten clinical recovery and minimize pulmonary dysfunction. PMID- 8203973 TI - Planned ventral hernia. Staged management for acute abdominal wall defects. AB - OBJECTIVE: Analysis of a staged management scheme for initial and definitive management of acute abdominal wall defects is provided. METHODS: A four-staged scheme for managing acute abdominal wall defects consists of the following stages: stage I--prosthetic insertion; stage II--2 to 3 weeks after prosthetic insertion and wound granulation, the prosthesis is removed; stage III--2 to 3 days later, planned ventral hernia (split thickness skin graft [STSG] or full thickness skin and subcutaneous fat); stage IV--6 to 12 months later, definitive reconstruction. Cases were evaluated retrospectively for benefits and risks of the techniques employed. RESULTS: Eighty-eight cases (39 visceral edema, 27 abdominal sepsis, 22 abdominal wall resection) were managed during 8.5 years. Prostheses included polypropylene mesh in 45 cases, polyglactin 910 mesh in 27, polytetrafluorethylene in 10, and plastic in 6. Twenty-four patients died from their initial disease. The fistula rates associated with prosthetic management was 9%; no wound-related mortality occurred. Most wounds had split thickness skin graft applied after prosthetic removal. Definitive reconstruction was undertaken in 21 patients in the authors' institution (prosthetic mesh in 12 and modified components separation in 9). Recurrent hernias developed in 33% of mesh reconstructions and 11% of the components separation technique. CONCLUSIONS: The authors concluded that 1) this staged approach was associated with low morbidity and no technique-related mortality; 2) prostheses placed for edema were removed with fascial approximation accomplished in half of those cases; 3) absorbable mesh provided the advantages of reasonable durability, ease of removal, and relatively low cost--it has become the prosthesis of choice; and 4) the modified components separation technique of reconstruction provided good results in patients with moderate sized defects. PMID- 8203974 TI - Does routine stress-thallium cardiac scanning reduce postoperative cardiac complications? AB - OBJECTIVE: Prophylactic cardiac revascularization in patients with ischemic myocardium could reduce postoperative cardiac complications after aortic reconstruction. However, the effectiveness of this approach has not been documented. SUMMARY BACKGROUND DATA: Stress-thallium scanning can identify patients with ischemic myocardium. Morbidity and mortality after aortic reconstruction appears to be largely caused by co-existent coronary artery disease, and patients who have had recent cardiac revascularization have few postoperative cardiac complications. METHODS: Preoperative stress-thallium scanning was evaluated prospectively in 146 patients undergoing aortic reconstruction. Patients with positive studies underwent coronary arteriography and cardiac revascularization, when appropriate. Postoperative cardiac complications and long-term survival in these patients were compared with results from 172 similar patients undergoing aortic reconstruction without stress thallium scanning. Results also were analyzed to determine predictors of postoperative cardiac events. RESULTS: Forty-one per cent of patients undergoing stress-thallium testing underwent coronary arteriography, and 11.6% had cardiac revascularization. In contrast, 14.7% of patients treated without stress-thallium testing had coronary arteriography, and 4.1% had revascularization (p < 0.01). Despite this, cardiac mortality, serious cardiac complications, and long-term cardiac mortality were similar in both groups. Only advanced age and intraoperative complications (but not a positive stress-thallium test) predicted postoperative cardiac events. CONCLUSIONS: Preoperative stress-thallium testing confirmed a high incidence of significant coronary artery disease in patients undergoing aortic reconstruction, but prophylactic cardiac intervention does not reduce operative or long-term mortality. Thus, the risk and expense of routine stress-thallium testing and subsequent cardiac revascularization cannot be justified. PMID- 8203975 TI - Cryopreserved saphenous vein allografts for below-knee lower extremity revascularization. AB - OBJECTIVE: Cryopreserved saphenous vein allografts have been offered as an alternative conduit for bypass in ischemic limbs. The authors examined the efficacy of this conduit for arterial bypass to the distal popliteal and tibial arteries in patients in whom autogenous vein was not available. SUMMARY BACKGROUND DATA: Previous experience with arterial and venous allografts has been unsatisfactory because of aneurysmal degeneration and poor patency. Endothelial loss and host rejection have been suggested as mechanisms of graft failure. Cryopreservation by modern techniques with rate controlled freezing, dimethyl sulfoxide (DMSO), and other cryopreservants, has addressed these issues and rekindled interest in vein allografts. METHODS: Over a period of more than 5 years, 115 cryopreserved vein allografts were implanted in 87 limbs to the distal popliteal (14) or tibial (101) arteries. The indication for surgery was rest pain in 56 procedures (49%), gangrene in 36 (31%), claudication in 21 (18%), and replacement of aneurysmal allografts in 2. Follow-up was 1 to 61 months (mean 25 months). RESULTS: There was no significant difference in patency related to site of proximal or distal anastomosis, patency of runoff vessels, use of anticoagulation, age, sex, diabetes, hypertension, smoking, indication, source of graft, or use of multiple segments. Revision was required in six grafts for aneurysmal dilatation. Histologic examination of explanted sections of allografts showed no immune response, and immunosuppressive drugs were not used. CONCLUSIONS: Although limb salvage has been satisfactory, long-term patency rates for cryopreserved vein allografts are poor when compared with autogenous vein. The cost of cryopreserved allografts far exceeds that of prosthetic grafts, for which comparable and superior results have been reported. Use of cryopreserved vein allografts should be reserved for situations in which adequate lengths of autogenous vein do not exist and the risk of infection of prosthetic grafts is high. PMID- 8203976 TI - Subclavian revascularization. A quarter century experience. AB - OBJECTIVE: Twenty-five years of experience with subclavian revascularizations were reviewed to determine the long-term patency rates of different extrathoracic approaches. SUMMARY BACKGROUND DATA: Although it is generally agreed that proximal subclavian stenosis should be treated by an extrathoracic route whenever possible, the optimum procedure is debated. Alternatives include subclavian carotid bypass, subclavian-to-subclavian or axillo-axillary bypasses, and the authors' preferred technique of subclavian carotid transposition (SCT). METHODS: Records were researched for the past 25 years in a single specialty surgical clinic for extrathoracic subclavian revascularizations. One hundred ninety such procedures were identified, and hospital charts and office medical records were reviewed for procedure, preoperative symptoms, blood pressure differentials, and postoperative complications. Patency was determined by physical examination, differential blood pressures, Doppler spectral analysis, duplex examinations, and arteriography. RESULTS: Bypass procedures were used infrequently, and although the results are reported, they are excluded from any analysis. Subclavian carotid transposition was used in 178 procedures. All anastomoses were found to be patient at follow-up, except for one, which failed at 26 months. Mean follow-up was 46 months, with five patients lost to follow-up. Overall mortality rate was 2.2%, with the mortality falling to 1.1% if only subclavian carotid transposition patients are included. CONCLUSIONS: Subclavian carotid transposition should be the treatment of choice for routine subclavian carotid occlusive disease because of its exceptional long-term patency and low morbidity. PMID- 8203977 TI - Insulin regulation of hepatic glucose transporter protein is impaired in chronic pancreatitis. AB - OBJECTIVE: The effect of chronic pancreatitis and insulin on the expression of the hepatic facilitative glucose transporter protein (GLUT-2) was determined in rats. SUMMARY BACKGROUND DATA: Chronic pancreatitis is associated with diabetes mellitus or impaired glucose tolerance. Suppression of hepatic glucose production (HGP) by insulin is impaired, although the mechanism is unknown. METHODS: Normal rats, rats with chronic pancreatitis induced 12 to 16 weeks earlier by oleic acid injection into the pancreatic ducts, and sham-operated rats were studied. Isolated, single-pass liver perfusion was performed, during which glucagon (1.2 pM) was infused, with or without insulin (0.6 or 1.2 nM). The suppression of HGP production by insulin was compared with changes in GLUT-2 in the membrane fraction of liver biopsies obtained before and after hormone perfusion. RESULTS: Glycogen-rich (fed) livers of normal rats (n = 16) demonstrated a dose-dependent suppression of hepatic glucose production by insulin (50 +/- 5% HGP induced by glucagon alone during 1.2-nM insulin perfusion) and a dose-dependent decrease in GLUT-2 (30 +/- 13% of basal level during 1.2-nM insulin perfusion). Sham-operated rats (n = 6) also showed reductions in HGP (51 +/- 4%) and GLUT-2 (14 +/- 10%) during 1.2-nM insulin perfusion. In contrast, rats with chronic pancreatitis (n = 6) showed no suppression of HGP during 1.2-nM insulin perfusion, and an increase in GLUT-2 (+20 +/- 6%) after insulin perfusion (p < 0.02 vs. sham). CONCLUSIONS: Insulin suppresses glucagon-stimulated HGP in normal and sham-operated rats, and this reduction in HGP is associated with a decrease in the membrane-bound quantity of GLUT-2. In chronic pancreatitis, insulin suppression of HGP is absent, and this is accompanied by an increase in GLUT-2 in the hepatocyte membrane. The authors conclude that the insulin-mediated change in the level of hepatocyte GLUT-2 is impaired in chronic pancreatitis, and may contribute to the altered glucose metabolism observed commonly in this disease. PMID- 8203978 TI - Determination of endogenous cytokines in chronic wounds. AB - OBJECTIVE: This study objectively characterized the microenvironment of indolent, chronic wounds by developing a method by which minute quantities of cytokines could be extracted from chronic wounds and separately identified. SUMMARY BACKGROUND DATA: Recombinant DNA technology and the ability to clone compounds such as cytokines allow new management schemes for the treatment of acute and chronic wounds. Before treatment with an exogenous cytokine is started, it would be helpful to know the endogenous level of that cytokine in the wound. Although various methods of extracting cytokines from acute wounds have been reported, no techniques have existed to reliably measure endogenous levels of cytokines in chronic wounds. METHODS: Porous, inert hydrophilic dextranomer beads were tested for their ability to absorb or adsorb protein and cytokines in vitro with either albumin or albumin laced with various known amounts of cytokines, and then from chronic human pressure ulcers. The Bradford protein assay was used to determine protein levels. Enzyme-linked immunosorbent assay (ELISA) techniques were used to determine levels of platelet-derived growth factor (PDGF)-AB, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and transforming growth factor-Beta (TGF-beta) extracted by the beads. RESULTS: Between 88% and 98% of known amounts of albumin could be recovered. Similarly, more than 90% of the laced cytokines could be recovered. In 20 grade III/IV pressure ulcers, although protein concentrations were remarkably similar, endogenous levels of cytokine growth factors varied tremendously. Platelet-derived growth factor-AB ranged from 49 to 867 pg/mL; bFGF from 47 to 697 pg/mL; and EGF from nondetectable to 247.5 pg/mL. TGF-B was not detected in 17 of the 20 pressure ulcers. CONCLUSIONS: This new technique appears useful for measuring endogenous levels of cytokines. Levels of cytokines found in these chronic wounds are much lower than those reported from acute wounds. The marked variation found among the 20 wounds may help to explain the differences reported in recent wound healing trials with exogenous cytokines. PMID- 8203979 TI - Optimal timing of abdominal aortic aneurysm repair after coronary artery revascularization. AB - OBJECTIVE: The authors ascertained the optimal timing of repair of an abdominal aortic aneurysm (AAA) after coronary artery revascularization. SUMMARY BACKGROUND DATA: Cardiac events are the most common cause of death after elective repair of AAA. Preoperative coronary revascularization has significantly reduced postoperative cardiac complications after elective AAA repair. Currently, most patients undergo repair of asymptomatic AAA within 6 months after the coronary revascularization. METHODS: The authors performed a retrospective review of patients who underwent repair or scheduled repair of an asymptomatic AAA within 6 months after coronary artery bypass graft (CABG) between March 1988 and October 1993. RESULTS: There was no mortality in the group of patients (n = 14) who underwent repair of AAA simultaneously or within 14 days of coronary revascularization. In contrast, there was a significantly increased mortality rate of 3 of 9 (33%) in patients scheduled to undergo repair of the AAA more than 2 weeks after coronary revascularization (p < 0.05). All nonsurvivors died between 16 and 29 days after CABG, and died as a result of ruptured AAA. CONCLUSION: Elective AAA repair should be undertaken simultaneously or within 2 weeks of coronary artery revascularization because of an increased risk of postoperative AAA rupture seen after this time period. In addition, simultaneous or early postoperative AAA repair does not increase the overall operative risk. PMID- 8203980 TI - Hypothermic circulatory arrest for cerebral protection during combined carotid and cardiac surgery in patients with bilateral carotid artery disease. AB - OBJECTIVE: The authors evaluated the protective effect of hypothermic circulatory arrest for patients with bilateral carotid artery disease who underwent cardiac surgical procedures. SUMMARY BACKGROUND DATA: Severe bilateral carotid artery disease coexisting with cardiac disease that requires surgical treatment is associated with a substantial incidence of stroke after operations that require cardiopulmonary bypass. The optimal method of management of patients with these coexisting conditions is not established clearly. Because hypothermia has a protective effect on neural and myocardial tissue during cardiac operations, a protocol employing profound hypothermia and a period of circulatory arrest was evaluated in a group of patients who underwent combined carotid and cardiac surgery who were considered to be at increased risk for the development of stroke. METHODS: Fifty patients with bilateral carotid artery disease, including 24 patients with high-grade unilateral stenosis and contralateral occlusion and 6 patients with 80% to 99% bilateral stenosis, underwent combined carotid endarterectomy and cardiac surgery (coronary artery bypass grafting in all 50 patients and additional procedures in 8 patients). Profound systemic hypothermia (15 C) was instituted, and the carotid endarterectomy was performed during a period of circulatory arrest that averaged 30 minutes. The cardiac procedure was performed during the periods of cooling and rewarming. RESULTS: The 30-day mortality rate was 6% (3 patients). There were no early postoperative strokes or reversible ischemic neurologic deficits. There have been seven late deaths in the postoperative period, which extends to 54 months. None of these deaths were caused by stroke. There has been one late stroke, which occurred in the distribution of the unoperated carotid artery. CONCLUSIONS: This technique provides adequate protection of the brain and myocardium during combined carotid and cardiac surgical procedures and appears to reduce the frequency of stroke in the high-risk subgroup of patients with bilateral carotid artery disease. PMID- 8203981 TI - Ventricular aneurysmectomy. A 25-year experience. AB - OBJECTIVE: This study determined predictors of operative survival and improved long-term outcomes in patients undergoing ventricular aneurysmectomy. SUMMARY BACKGROUND DATA: Since the first successful repair of ventricular aneurysm in 1958, refined technique and improvement in perioperative care have been introduced to lower morbidity and mortality. METHODS: The authors reviewed their institutional experience from 1968 through 1993 in treating 523 patients who underwent ventricular aneurysmectomy. RESULTS: Overall operative mortality was 8% and overall median survival was 128 months. Contractility grade, age, and year of operation were predictors of operative mortality and of improved long-term survival. Type of aneurysm repair was not a strong predictor of operative mortality or improved long-term survival. CONCLUSIONS: Ventricular aneurysmectomy can be performed safely using one of a number of established techniques, although operative mortality and long-term survival may not depend on the techniques used. PMID- 8203982 TI - Growth hormone enhances amino acid uptake by the human small intestine. AB - OBJECTIVE: The effects of growth hormone (GH) on the luminal transport of amino acids and glucose by the human small intestine were investigated. SUMMARY BACKGROUND DATA: The anabolic effect of growth hormone administration is associated with nitrogen retention and an increase muscle strength, but the impact of growth hormone on nutrient uptake from the gut lumen has not been examined. METHODS: Twelve healthy patients received a daily subcutaneous dose of low-dose GH (0.1 mg/kg), high-dose GH (0.2 mg/kg), or no treatment (controls) for 3 days before surgery. At operation, ileum (8 patients) or jejunum (4 patients) was resected, and brush border membrane vesicles (BBMVs) were prepared by differential centrifugation. Vesicle purity was confirmed by a 16-fold enrichment of marker enzymes. The carrier-mediated transport of glutamine (System B), leucine (System L), alanine (System B), arginine (System y+), MeAIB (methyl alpha aminoisobutyric acid [System A]), and glucose (Na(+)-dependent glucose transporter) by BBMVs was measured by a rapid mixing/filtration technique. RESULTS: Treatment with low-dose GH resulted in a statistically insignificant increase in amino acid transport rates in jejunal and ileal BBMVs. High-dose GH resulted in a generalized 20%-to 70%-stimulation of amino acid transport, whereas glucose transport was not affected. The effects of GH were similar in ileum and jejunum. Kinetic analysis of the transport of glutamine (the most abundant amino acid in the body and the principal gut fuel) and the essential amino acid leucine revealed that the increase in transport was caused by a 50% increase in carrier Vmax, consistent with an increase in the number of functional carriers in the brush border membrane. Pooled analysis of transport velocities demonstrated that total rates of amino acid uptake from the gut lumen were increased significantly by 35% in GH-treated patients. CONCLUSIONS: The ability of GH to enhance amino acid uptake from the gut lumen provides energy and precursors for protein synthesis in the gut mucosa, as well as additional substrate for anabolism in other organs. PMID- 8203983 TI - A prospective randomized trial comparing open versus laparoscopic appendectomy. AB - OBJECTIVE: The authors determined whether there was an advantage to laparoscopic appendectomy when compared with open appendectomy. SUMMARY/BACKGROUND DATA: The advantages of laparoscopic appendectomy versus open appendectomy were questioned because the recovery from open appendectomy is brief. METHODS: From January 15, 1992 through January 15, 1993, 75 patients older than 9 years were entered into a study randomizing the choice of operation to either the open or the laparoscopic technique. Statistical comparisons were performed using the Wilcoxon test. RESULTS: Thirty-seven patients were assigned to the open appendectomy group and 38 patients were assigned to the laparoscopic appendectomy group. Two patients were converted intraoperatively from laparoscopic appendectomies to open procedures. Thirty-one patients (81%) in the open group had acute appendicitis, as did 32 patients (84%) in the laparoscopic group. Mean duration of surgery was 65 minutes for open appendectomy and 87 minutes for laparoscopic appendectomy (p < 0.001). There were no statistically significant differences in length of hospitalization, interval until resumption of a regular diet, or morbidity. Duration of both parenteral and oral analgesic use favored laparoscopic appendectomy (2.0 days versus 1.2 days, and 8.0 days versus 5.4 days, p < 0.05). All patients were instructed to return to full activities by 2 weeks postoperatively. This occurred at an average of 25 days for the open appendectomy group versus 14 days for the laparoscopic appendectomy group (p < 0.001). CONCLUSIONS: Patients who underwent laparoscopic appendectomies have a shorter duration of analgesic use and return to full activities sooner postoperatively when compared with patients who underwent open appendectomies. The authors consider laparoscopic appendectomy to be the procedure of choice in patients with acute appendicitis. PMID- 8203984 TI - Laparoscopic-assisted colectomy. Initial experience. AB - OBJECTIVE: The authors studied the results of laparoscopic colectomies performed by a surgical team on 80 consecutive patients and compared these results with standard open colectomies. METHODS: Eight consecutive laparoscopic-assisted colectomies were performed by Norfolk Surgical Group in a 14-month period and compared to 53 patients who had a conventional open colectomies. Analysis included indications for surgery, types of procedure, complications, incidence and causes for conversion, length of procedure, duration of postoperative ileus, hospital stay, operating room and total hospital charges, and examination of the pathologic specimens. RESULTS: Many different types of colectomies were performed successfully and safely for a variety of surgical indications. The conversion rate was 22.5%, which decreased to 15% in the second half of the series. Complications in patients who underwent laparoscopic operations were not severe in number of type. The length of the operative procedure, operating room charge, and the total hospital charge were greater for patients undergoing laparoscopic assisted colectomies. Patients who underwent laparoscopic operations had a shorter period of postoperative ileus and less pain, resumed a regular diet sooner, and were discharged from the hospital sooner than patients who underwent open colectomies. There was no significant difference in the pathology specimens obtained by laparoscopic-assisted colectomies compared with conventional open colectomies for length of specimen, surgical margins, and number of lymph nodes retrieved. CONCLUSIONS: This study indicated that laparoscopic techniques can be applied safely and effectively to a broad range of colonic operations. Laparoscopic-assisted colectomies take longer to perform and are more costly, but are associated with less paralytic ileus, less pain, and reduced hospital stay. Laparoscopic colectomies for the treatment of malignancy are achievable technically, but will require careful long-term study. PMID- 8203985 TI - Common bile duct evaluation in the era of laparoscopic cholecystectomy. 1050 cases later. AB - OBJECTIVE: The authors documented the evolution of common bile duct (CBD) evaluation after the development of laparoscopic cholecystectomy (LC) and CBD exploration. Emphasis was placed on stratification of CBD stone risk so that subgroups could be selected appropriately for no further studies, preoperative endoscopic retrograde cholangiogram (ERC), or intraoperative intervention. METHODS: Data were accumulated by the authors on presentation, findings, and outcomes of 1050 patients who underwent cholecystectomies. Risk stratification was based on the history, ultrasound findings, biochemical derangements, and operative findings. RESULTS: Fifty-seven per cent of patients met criteria to be "no/low" risk for CBD stones (CBD diameter < 5 mm, normal liver enzymes, and no history of acute cholecystitis, jaundice, or pancreatitis); in these patients, cholangiograms were not obtained, and there was no clinical evidence of CBD stones observed in follow-up at 45 months (sensitivity = 100%). As techniques developed for laparoscopic CBD exploration, there was a decreased incidence of open cholecystectomy (p < 0.05) and preoperative ERC (p < 0.05). The rate of operative cholangiogram increased from 13% to 23% during the series (p < 0.01). There were no CBD injuries or late strictures. The only bile leak occurred from a peripheral segmental duct in the gallbladder bed and was resolved with a laparotomy and suture. There were no transfusions. Three retained stones were documented in patients who had false-normal operative cholangiograms. CONCLUSIONS: Criteria were defined that delineate a "no/low" risk group of LC patients for whom operative cholangiograms were not indicated for excluding CBD stones. The routine use of operative cholangiography as a means of preventing CBD injury was not substantiated by this study. The indications for preoperative ERC should continue to decrease as laparoscopic techniques evolve. PMID- 8203986 TI - Lessons learned from clinical trials on monoclonal anti-endotoxin antibody. PMID- 8203987 TI - Effects of calcium antagonists on renal hemodynamics and progression of nondiabetic chronic renal disease. AB - In recent years, substantial investigative attention has focused on therapeutic regimens that could retard the progression of chronic renal insufficiency. Emphasis has been placed on the effects of antihypertensive treatment on renal hemodynamics and preservation of renal function. It has been suggested that some classes of antihypertensive agents may confer a greater renoprotective effect, especially agents that lower glomerular capillary pressure. Conversely, by virtue of their ability to preferentially dilate the afferent arteriole calcium antagonists theoretically could favor an increase in glomerular capillary pressure thereby accelerating the decline of renal function. In this review we survey the literature critically and conclude that in patients with essential hypertension and in patients with chronic renal insufficiency, calcium antagonists effectively reduce systemic blood pressure while maintaining glomerular filtration rate and effective renal plasma flow. Preliminary results from a few long-term studies suggest that calcium antagonists may even attenuate the decline in renal function of patients with chronic renal failure. The majority of studies in humans, however, have been nonrandomized, of too short duration, or confounded by investigative difficulties precluding definite conclusions whether calcium antagonists have renoprotective effects. Although the possibility that calcium antagonists may retard progression of renal disease remains to be ascertained, the available evidence indicates that calcium antagonists may be used in patients with renal functional impairment without further exacerbating renal function. PMID- 8203988 TI - Increasing incidence of cancer of the prostate. The experience of black and white men in the Detroit metropolitan area. AB - BACKGROUND: Prostate cancer mortality and incidence rates have been gradually increasing for decades in the United States, with an accelerated increase in incidence noted in the past several years. This study explores in detail the occurrence of prostate cancer in southeast Michigan from 1973 through 1991. METHODS: Data from the National Cancer Institute Surveillance, Epidemiology, and End Results program are analyzed with emphasis on time trends by race, age, stage, and treatment. RESULTS: Population-based rates for prostate cancer increased by 70% between 1988 and 1991. Increases are most pronounced for early stage disease and among whites compared with blacks. Corresponding increases in treatment with radical prostatectomy are also observed. CONCLUSION: Increased incidence of prostate cancer is likely a result of widespread use of prostate specific antigen. PMID- 8203989 TI - Is cost a barrier to screening mammography for low-income women receiving Medicare benefits? A randomized trial. AB - BACKGROUND: In 1991, Medicare began covering screening mammograms subject to copayment and deductible. This study evaluated the effectiveness of Medicare in removing financial barriers to screening mammography among low-income older women. METHODS: In an inner-city public hospital's General Medicine Clinic, 119 consecutive, eligible, and consenting Medicare-enrolled women without known risk factors for breast cancer other than age, and no mammogram in the previous 2 years, were entered into a randomized controlled trial with follow-up after 2 months. The mean age was 71 years; 77% were black, 92% had an annual income below $10,000, and 52% had had a previous mammogram. All patients were counseled concerning indications for screening mammograms and Medicare coverage, and all were referred to a low-cost mammography facility. Sixty-one subjects were randomly assigned a voucher for a free screening mammogram at the referral facility. Obtaining a mammogram within 60 days of study entry was the main outcome measure. RESULTS: Of the women given vouchers, 27 (44%) obtained screening mammograms, compared with six (10%) of those without vouchers (P < .001). Adjustment by multiple logistic regression confirmed this association, yielding an adjusted odds ratio of 7.4 (95% confidence interval, 2.5 to 21.4). Knowledge concerning mammography and breast cancer increased significantly overall (and within randomization groups) between initial interview and follow up; fear did not change. For women without the voucher, the main reason for not obtaining a mammogram was financial; the main reason for women with the voucher was transportation. CONCLUSION: In a low-income, inner-city population of older women, financial barriers to screening mammography persist despite Medicare coverage. PMID- 8203990 TI - Curative transcatheter radiofrequency current ablation for atrioventricular nodal reentry tachycardia. AB - BACKGROUND: To evaluate the efficacy of atrioventricular nodal modification by transcatheter ablation using radiofrequency energy in preventing electrically inducible and spontaneous symptomatic atrioventricular nodal reentry tachycardia, a prospective, nonrandomized, "before-after" trial was performed. Fifty consecutive patients with recurrent spontaneous symptomatic atrioventricular nodal reentry tachycardia referred to the Massachusetts General Hospital, Boston, were recruited. METHODS: A diagnostic intracardiac electrophysiologic study was performed to define the mechanism of each patient's supraventricular tachycardia. Thereafter, selective ablation of one or more slow atrioventricular nodal pathways was attempted in 47 patients, and in three patients selective ablation of a retrograde fast atrioventricular nodal pathway was carried out. Repeated programmed cardiac stimulation was performed 30 minutes after catheter ablation therapy and, where possible, before hospital discharge to evaluate the presence of electrically inducible supraventricular tachycardia. RESULTS: Electrically inducible atrioventricular nodal reentry tachycardia was eliminated in all 50 patients. No patient developed early heart block. During a mean (+/- SD) follow up period of 8.9 +/- 5.3 months, three patients experienced a recurrence of spontaneous atrioventricular nodal reentry tachycardia and underwent a successful second ablation procedure. Two patients required permanent pacemaker implantation, one for symptomatic first-degree atrioventricular block and one for late complete heart block. CONCLUSIONS: Catheter ablation of slow atrioventricular nodal pathways by means of radiofrequency current is a safe and effective technique for eliminating electrically inducible and spontaneous atrioventricular nodal reentry tachycardia. PMID- 8203991 TI - Projected impact of monoclonal anti-endotoxin antibody therapy. AB - BACKGROUND: The goals of this study were to evaluate the criteria for administration of HA-1A monoclonal antibody therapy from the HA-1A trial in patients with suspected gram-negative bacteremia and to evaluate the accuracy with which Bone's criteria for sepsis syndrome identify patients with gram negative bacteremia. METHODS: This prospective cohort study included 1509 episodes in which hospitalized patients had blood cultures performed in an urban tertiary-care hospital. The main outcome measures were gram-negative bacteremia and gram-negative sepsis. RESULTS: Of 1509 episodes, 115 (8%) represented bacteremia and 40 (3%) included gram-negative rods. Of these 40 patients, nine died in the hospital, including five patients who had gram-negative sepsis; all five had another rapidly fatal disease. Using criteria for treatment and exclusions from the HA-1A trial, three of the patients with gram-negative bacteremia would have been treated, while at least 52 patients without gram negative bacteremia might have received HA-1A therapy (positive predictive value of criteria, 5.5%). Of the 1509 episodes, sepsis syndrome as defined by Bone was present in 34 (2.3%). While 32 of the 34 patients had suspected gram-negative bacteremia, only five had blood cultures positive for gram-negative bacteria. CONCLUSIONS: In this population, current criteria for administration of monoclonal anti-endotoxin antibody therapy were not sensitive or specific for gram-negative bacteremia, and many patients with gram-negative sepsis were too ill from other conditions to benefit. Indiscriminate use of these therapies could thus be costly yet yield few benefits. To identify patients who should receive novel therapies, better risk-stratification methods and cost-effectiveness analysis are needed. PMID- 8203992 TI - The Rochester practice-based experience. An experiment in medical education. AB - BACKGROUND: Recent changes in the organization and financing of medical practice have resulted in a shift of patient care from the hospital to ambulatory locations and dramatically changed the mix and severity of the inpatient population. Medical educators are concerned that hospitalized patients are not truly representative of the practice of internal medicine and may be unsuitable for the education of third-year medical students. The University of Rochester (NY) Department of Medicine recently established a "practice-based" component to complement the inpatient segment of the third-year medicine clerkship. METHODS: Participating students work with a practicing internist for the second half of the 12-week clerkship. Students evaluate office and hospital patients in the internist's practice and attend didactic conferences. We used a multi-measurement curriculum evaluation system to assess the new program and compare it with the established hospital experience. Evaluation components included the following: logs in which students profiled their clinical activities; questionnaires that assessed opinions and satisfaction about the clerkship; group interviews with students; and visits to practice-based sites to interview both preceptor and student. RESULTS: Practice-based students saw many more patients with a broader range of illnesses and had more observation and supervision from faculty than hospital-based students. Practice-based students discussed all of their patients with their preceptors, who were perceived as being excellent teachers. Hospital based students, although generally positive, were also generally less enthusiastic about the amount and quality of teaching, observation, and supervision. Practice-based and hospital-based students achieved similar grades on the final examination and received a similar number of honors grades. Preceptors were enthusiastic in their endorsement of the practice-based experience and patient acceptance of students was high. CONCLUSION: The practice based experience is feasible and of equal academic rigor to the hospital experience. This realistic immersion into the daily activities of an internist provides an enriching balance to the traditional hospital-based clerkship. PMID- 8203994 TI - High prevalence of colonic polyps in patients with acromegaly. Influence of sex and age. AB - BACKGROUND: An association between acromegaly and colonic polyps has been reported, although risk factors are still uncertain. METHODS: Full colonoscopy was performed with a fiberoptic colonoscopy on 31 acromegalic patients, 11 men and 20 women aged 27 to 85 years (mean, 52.2 years), and on 236 subjects, 127 men and 109 women aged 23 to 84 years (mean, 50.1 years), referred for hemorrhoids, who were considered controls. The colonoscopic findings were evaluated in relation to demographic, clinical, and hormonal data pertaining to the two groups. RESULTS: The prevalence of either adenomatous or hyperplastic polyps was higher in acromegalic patients than in controls (38% vs 14% and 26% vs 10%, respectively; P < .001, respectively). Acromegalics with and without colonic adenomas did not differ significantly in growth hormone and insulinlike growth factor I levels or duration of acromegalic disease and its status (activity or remission); however, patients with adenoma were younger (median age, 50.5 vs 59 years; range, 27 to 85 years vs 39 to 66 years; P < .05). An opposite age pattern was observed in the control group. Indeed, the prevalence of adenoma in acromegalic patients was much higher than that in controls among those less than 50 years of age (46% vs 7%, P < .001); the difference was less remarkable at older ages. Adenomatous polyps were more frequently found in male subjects, in both patients and controls (45% vs 33% [not significant] and 19% vs 9% [P < .05], respectively). CONCLUSIONS: Acromegaly may carry an increased risk of colonic adenoma, especially in younger patients, who usually display more aggressive disease. A smaller increase in risk was observed in elderly patients, in whom disease is reportedly milder. We suggest that acromegalic patients should undergo screening colonoscopy. PMID- 8203993 TI - Effects of beef and chicken consumption on plasma lipid levels in hypercholesterolemic men. AB - BACKGROUND: The recommendation to lower saturated fat intake is often interpreted as requiring the elimination of beef to control or lower serum cholesterol levels. The study hypothesis was that the Step I Diet (8% to 10% of energy intake from saturated fatty acids) containing beef would have the same effect on plasma lipid levels of hypercholesterolemic men as a like diet containing chicken. METHODS: Thirty-eight free-living hypercholesterolemic (otherwise healthy) men completed a 13-week dietary intervention study. Subjects consumed their usual diets for 3 weeks, followed by a 5-week stabilization diet (18% of energy intake from saturated fatty acids), before randomization to one of two test diets for 5 weeks. The test diets contained either 85 g of cooked beef (8% fat) or 85 g of cooked chicken (7% fat) per 4184 kJ and had 7% to 8% of energy from saturated fatty acids. All food was supplied during the stabilization and test diets. RESULTS: The beef and chicken test diets both produced significant decreases in average plasma total cholesterol level (0.54 mmol/L [7.6%] for beef and 0.70 mmol/L [10.2%] for chicken) and low-density lipoprotein cholesterol level (0.46 mmol/L [9%] for beef and 0.55 mmol/L [11%] for chicken). Changes in average levels of plasma total cholesterol, high-density lipoprotein cholesterol, triglyceride, and low-density lipoprotein cholesterol were not statistically different (smallest P = .26) between the beef and chicken test diets. The average triglyceride level did not change for either test diet group. CONCLUSIONS: In this short-term study, comparably lean beef and chicken had similar effects on plasma levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride. We concluded that lean beef and chicken are interchangeable in the Step I Diet. PMID- 8203995 TI - Active and passive smoking are associated with increased carotid wall thickness. The Atherosclerosis Risk in Communities Study. AB - BACKGROUND: Active cigarette smoking has been established as a potent risk factor for carotid atherosclerosis in clinical populations; however, neither the role of active smoking in general populations nor the impact of environmental tobacco smoke has been well described. METHODS: The association between carotid artery wall thickness and cigarette smoking was studied in 12,953 black and white men and women, aged 45 to 65 years, examined in the Atherosclerosis Risk in Communities Study. Participants were classified as current smokers (n = 3525), past smokers (n = 4315), never smokers reporting weekly exposure to environmental tobacco smoke (ETS or "passive smoking") of at least 1 hour (n = 3339), or never smokers reporting no weekly exposure to ETS (n = 1774). Carotid artery intimal medial thickness (IMT) was measured by B-mode ultrasound. RESULTS: Increased IMT was observed in each category, in order from smallest to greatest increase: never smokers not exposed to ETS, never smokers exposed to ETS, past smokers, and current smokers. The larger IMT observed in the nonsmoking group exposed to ETS compared with the nonsmokers not exposed persisted after control for diet, physical activity, body mass index, alcohol intake, education, and major cardiovascular risk factors. Among past and current smokers, increased pack-years of exposure was associated with increased IMT. Among nonsmoking men exposed to ETS, there was a significant increase in IMT with increasing number of hours per week of ETS exposure. CONCLUSIONS: These data confirm the strong relationship between active smoking and carotid artery IMT and provide initial evidence that passive smoking exposure is related to greater IMT. Increasing exposure to cigarette smoke (either pack-years of active smoking or hours of ETS) was significantly related to increased IMT. PMID- 8203996 TI - Stiff-man syndrome. Report of a case. AB - Stiff-man syndrome is a well-described, but rare and often overlooked, neuromuscular syndrome of rigidity, spasm, and gait abnormality that is associated with several endocrinologic and autoimmune disorders. A patient exhibiting many typical features of stiff-man syndrome had intermittent symptoms for 22 years before the correct diagnosis was made. Similar to many described patients, she was diabetic, hyperthyroid, and had elevated islet cell, antithyroid, and glutamic acid decarboxylase antibody levels. The high frequency of diabetes mellitus among patients with stiff-man syndrome is emphasized, as is increasing evidence to suggest that elaboration of anti-glutamic acid decarboxylase and anti-islet cell antibodies may play a role in the pathophysiologic state of the disorder. PMID- 8203997 TI - Universal cardiopulmonary resuscitation--a flawed standard of practice. PMID- 8203998 TI - Wider meaning for lactate dehydrogenase in acquired immunodeficiency syndrome. PMID- 8203999 TI - Bedside monitoring of blood glucose: is better "bad"? PMID- 8204000 TI - Postmortem blood cultures. PMID- 8204001 TI - Diagnostic utility of postmortem blood cultures. PMID- 8204002 TI - Pulmonary resection for metastatic germ cell tumors. PMID- 8204003 TI - Idiopathic thrombocytopenic purpura and accessory spleens. PMID- 8204004 TI - Inpatient phlebotomy practices. A College of American Pathologists Q-Probes quality improvement study of 2,351,643 phlebotomy requests. AB - We report outcomes of requests for inpatient phlebotomy procedures from 683 institutions participating in the College of American Pathologists Q-Probes programs. Of the 2,351,643 phlebotomy requests analyzed, 93.2% of venipunctures were successful, 1.6% were unsuccessful, 0.4% were partially successful, and 4.9% were not attempted by the assigned phlebotomist. Administrative inefficiencies prevented the assigned phlebotomist from attempting these venipunctures of which the most frequent reasons were patient unavailability (1.4%), patient transferred or discharged (0.9%), followed by the specimen already collected by someone else (0.7%). These results suggest that performance improvement of phlebotomy services, in general, would achieve the greatest gains by focusing attention to specific processes associated with administrative inefficiencies identified, rather than phlebotomists' technical skills. PMID- 8204005 TI - Neuroepithelioma (primitive neuroectodermal tumor) and Ewing's sarcoma. At least a partial consensus. PMID- 8204006 TI - Comparison of Ewing's sarcoma of bone and peripheral neuroepithelioma. An immunocytochemical and ultrastructural analysis of two primitive neuroectodermal neoplasms. AB - Ewing's sarcoma of bone (ESB) and peripheral neuroepithelioma (PN) are frequently considered to be different tumors. Some researchers have suggested that PN is morphologically a neuroectodermal Ewing's sarcoma. We sought to determine the extent of neuroectodermal features in conventional ESB on direct patient material (25 cases) and to compare these tumors with a similar group of readily diagnosed PNs (10 cases). Light microscopic, ultrastructural, and immunophenotypic parameters were assessed and compared for both groups. The avidin-biotin complex method was used. All tumors were antigenically intact since all stained for vimentin or at least one marker. Neuroectodermal antigens (neuron-specific enolase, Leu-7 [HNK-1], neurofilament 200 kd, and S100) were found in nine of 10 cases of PN and in 17 of 25 cases of ESB. In ESB, an atypical light microscopic appearance correlated with the presence of neuroectodermal features in most cases, but neuroectodermal phenotype was more frequent (68%) than morphological evidence of neuroectodermal differentiation (36%). These data support the concept that ESB and PN are both peripheral primitive neuroectodermal neoplasms, differing only in extent of neuroectodermal phenotype and morphological differentiation. PMID- 8204007 TI - BCL-2 proto-oncogene expression in prostate cancer and its relationship to the prostatic neuroendocrine cell. AB - Prostatic adenocarcinoma has a divergent response to androgen ablation and a varied long-term prognosis. BCL-2 is a proto-oncogene that prevents programmed cell death. Since androgen withdrawal induces apoptosis, it has been postulated that BCL-2 may play a role in androgen resistance. Neuroendocrine cells have been demonstrated in prostate cancer and have an adverse influence on long-term prognosis. This study demonstrates a proportional relationship between the tissue levels of BCL-2 and the neuroendocrine marker, neuron-specific enolase in 11 of 13 cases of primary prostate cancer. This relationship does not appear to exist in metastatic prostate cancer or in most nonprostate cancers. Direct immunohistochemical staining confirmed BCL-2 in six of the primary tumors, and these BCL-2-containing cells appeared to be intimately associated with tumor neuroendocrine cells. PMID- 8204008 TI - Morphometric analysis of colorectal dysplasia with image processing. AB - Nuclear and structural abnormalities on the histological specimens of colorectal dysplasias were quantified by using 10 parameters. From the measured values, the following histological findings were obtained: progression from mild to severe dysplasia was associated with an increase in nuclear size, and nuclear arrangement became more irregular. There was, however, no difference between the nuclear size and arrangement in severe dysplasia and those in carcinoma. The nuclei were spindle shaped in mild and moderate dysplasia. On the other hand, they were relatively round in severe dysplasia and carcinoma. Structural abnormalities tended to increase with the histological abnormalities. These results correspond well with the histological abnormalities by which the pathologists grade dysplasia and diagnose carcinoma subjectively. Therefore, these 10 parameters might be useful for quantifying histological characteristics of colorectal dysplasias. PMID- 8204009 TI - Estrogen receptor detection in paraffin sections of adenocarcinoma of the colon, pancreas, and lung. AB - We performed a retrospective analysis for the presence of estrogen receptors (ERs) in known cases of adenocarcinoma of the colon, pancreas, and lung. Estrogen receptor status was determined by immunohistochemical methods using the ER-ICA (Abbott Laboratories, North Chicago, Ill) antibody on paraffin sections. None of 43 colon and 18 pancreatic adenocarcinomas demonstrated ERs by this method. Three of 42 lung adenocarcinomas exhibited some degree of nuclear staining for ERs. When evaluating an adenocarcinoma of unknown primary site, the ER-ICA antibody can be useful when included in a panel of antibodies. Positive results tend to exclude colonic or pancreatic, but not pulmonary, primary sites. PMID- 8204010 TI - Novel immunohistochemical localization of 28,000 molecular-weight (Mr) calcium binding protein (calbindin-D28k) in enterochromaffin cells of the human appendix and neuroendocrine tumors (carcinoids and small-cell carcinomas) of the midgut and foregut. AB - Calbindin-D28k is a highly conserved 28,000 (dalton) molecular-weight (Mr) calcium binding protein with broad tissue distribution, yet cell-type-specific expression predominantly in subpopulations of central and peripheral nervous system neurons, distal tubular cells of the kidney, and enteric neuroendocrine cells. A polyclonal antiserum against rat renal calbindin-D28k and a monoclonal antibody to calbindin-D28k purified from chicken intestine (clone CL-300) were used for immunohistochemical evaluation of formalin-fixed, paraffin-embedded tissues from multiple areas of the human small and large intestines and 93 primary neoplasms of the gastrointestinal tract (foregut, midgut, and hindgut derivatives) and the lung (foregut derivative). Calbindin-D28k immunostaining was obtained in a minority of enterochromaffin (neuroendocrine) cells, predominantly of the appendix and small intestine, as well as in autonomic neurons of the neural plexuses. Focal cytoplasmic Golgi-type staining was obtained with monoclonal antibody CL-300 in the appendiceal surface epithelium and dendritic macrophages confined to the appendiceal lymphoid follicles. Epithelial progenitor cells in enteric crypts and absorptive, goblet, and Paneth cells were calbindin D28k negative, while no immunoreactivity was demonstrated in the mucosae of the colon and rectum. Calbindin-D28k staining was consistently detected in subpopulations of neuroendocrine phenotypes in midgut (appendiceal/ileal) and foregut (bronchial) carcinoids and small-cell carcinomas, but was absent in adenocarcinomas, squamous cell carcinomas, leiomyomas/leiomyosarcomas, schwannomas, and lymphomas. Our observations suggest that calbindin-D28k is a novel adjuvant neuroendocrine marker that is potentially useful in diagnostic tumor immunohistochemistry. PMID- 8204011 TI - Gastrointestinal tattoos. AB - Tattooing of the gastrointestinal tract is used to facilitate the relocation of biopsy sites or other sites of interest at the time of subsequent biopsy or surgery. Submucosal injection of sterile india ink produces a zone of blue-black coloration that is grossly visible from both the mucosal and serosal surfaces. The pathology of gastrointestinal tattoos has only been briefly mentioned previously in the medical literature. We report two cases of gastrointestinal tattooing: one that was done to mark the margin of resection in a patient with gastric lymphoma, and the second that occurred unintentionally following the administration of activated charcoal for drug overdosage in a patient with undiagnosed active inflammatory bowel disease. Unintentional tattooing of the gastrointestinal tract has, therefore, not been reported. PMID- 8204012 TI - Epithelioid angiosarcoma of the thyroid gland. Report of two cases. AB - We present two cases of epithelioid angiosarcoma of the thyroid gland from two patients in Slovenia. In both cases, the tumor appeared as a dominant nodule in a multinodular goiter. Histological appearance of the tumor was similar in both cases and characterized by large epithelioid tumor cells with numerous intracytoplasmic lumina, large nuclei, and very prominent nucleoli. Such cells formed vascular structures as well. Neoplastic cells were positive for factor VIII-associated antigen in both cases. Reaction to Ulex europaeus lectin was positive in one case, and characteristic ultrastructural features were seen in another case. In both cases, some neoplastic cells also showed keratin positivity. Angiosarcoma is a rare but definite possibility in a differential diagnosis of anaplastic thyroid tumors in Slovenia. PMID- 8204013 TI - Ovarian lymphoma and serous carcinoma of low malignant potential arising in the same ovary. A case report with literature review of 14 primary ovarian lymphomas. AB - Ovarian lymphoma was incidentally identified in the ovary of a 31-year-old patient who underwent surgical exploration for an ovarian mass. The 6-cm mass was a serous carcinoma of low malignant potential and was located in the same ovary with the lymphoma. The lymphomatous nodule measured 1.5 cm and was diagnosed as diffuse, large-cell lymphoma of B-cell phenotype. Careful search during surgery, as well as extensive postoperative workup, showed no evidence of spread of either tumor type beyond the ovary. In a small pilot study, we examined 37 randomly selected oophorectomy specimens to determine the possible occurrence of lymphoid tissue in the ovary that could serve as substrate for development of ovarian lymphoma. Variable numbers of lymphocytes were identified in 34 of 37 ovaries, mainly in association with common ovarian lesions. This finding and the clinicopathologic data of 14 other reported cases of ovarian lymphoma provide evidence that lymphomas can arise primarily in the ovary. PMID- 8204014 TI - Bilateral beta 2-microglobulin amyloidomas of the buttocks in a long-term hemodialysis patient. AB - Only two cases of beta 2-microglobulin amyloid tumors involving the buttocks have been reported in the world literature. We report a case of bilateral buttock amyloid tumors with associated carpal tunnel syndrome and pathologic fracture involving the femoral head. This unusual local bilateral manifestation of the beta 2-microglobulin amyloidosis develops late in the course of hemodialysis and may be initiated by chronic trauma. PMID- 8204015 TI - Thymoma with foci of medullary differentiation in an 11-year-old-boy. AB - We report a benign encapsulated thymoma in an 11-year-old boy. Histologically, it showed foci of medullary differentiation mimicking the normal corticomedullary thymic architecture. We emphasize the rarity of thymomas in children and the possibility of mistaking this uncommon pattern of thymoma for other mediastinal tumors. PMID- 8204016 TI - A case with primary gastric lymphoma producing IgM and IgG immunoglobulins. AB - We describe a primary gastric lymphoma with IgM kappa and IgG kappa types of immunoglobulin in the neoplastic cells. The neoplastic cells containing IgM were morphologically different from those containing IgG. The IgG-bearing cells had globular cytoplasmic inclusions, but IgM-bearing cells did not. The neoplastic cells had two Ig heavy-chain gene rearrangements, with a germline band and a single kappa light-chain gene rearrangement. Immunoglobulin expression with light chain restriction of the neoplastic cells and single light-chain gene rearrangement indicated that the morphologically different neoplastic cells were derived from a common progenitor. The expression of IgM and IgG and two rearrangement bands of immunoglobulin heavy-chain gene suggested that class switching might have occurred in the lymphoma cells. PMID- 8204017 TI - Gastric carcinoid tumor and its precursor lesions. Ultrastructural study of a case before and after antrectomy. AB - Antrectomy has been proposed as the preferential treatment of hypergastrinemic patients with nonantral gastric carcinoids since it removes the main growth factor for the tumors and their precursor lesions, ie, hypergastrinemia. To investigate the cellular basis of the mechanism for postantrectomy regression in nonantral endocrine cells, a light and electron microscopic morphometric study was performed in a case of enterochromaffinlike-cell gastric carcinoid associated with hypergastrinemia before and 4 and 10 months after antrectomy. The withdrawal of sustained hypergastrinemia obtained by antrectomy was associated with a progressive reduction of the volume density, cross-sectional area, and number of profiles of endocrine cells in the remaining nonantral mucosa, in which gastrin dependent proliferations were regarded as the carcinoid precursor lesions. Ultrastructural morphometry demonstrated that the changes selectively involved the enterochromaffinlike cells, ie, the specific cell target for the trophic action of gastrin and the usual component of gastric carcinoids. The volume fractions of enterochromaffin and X cells (producing serotonin and endothelin, respectively) were increased 10 months after antrectomy. Persistence of a modest elevation of gastrin levels, likely due to the occurrence of gastrin cells in areas of pyloric metaplasia of the nonantral mucosa, did not prevent the hypotrophic effects of antrectomy. PMID- 8204018 TI - Pulmonary veno-occlusive disease. Another vascular disorder associated with human immunodeficiency virus infection? AB - A variety of arterial lesions in both pulmonary and systemic circulations have been described in association with human immunodeficiency virus infection. Such lesions include plexogenic arteriopathy in patients with primary pulmonary hypertension and fibrocalcific arterial lesions described in a variety of organs. Lesions involving the pulmonary veins, however, have not been previously described. We report a case of pulmonary veno-occlusive disease in a 2-year-old child with human immunodeficiency virus infection. In view of the rarity of these vascular disorders, including pulmonary veno-occlusive disease, it seems unlikely for their association with human immunodeficiency virus infection to occur by chance alone. Further work is needed to elucidate the role that human immunodeficiency virus may have in the pathogenesis of such vascular lesions. PMID- 8204019 TI - Primary carcinoid tumor of the bladder arising beneath an inverted papilloma. AB - We describe a 54-year-old woman with a primary carcinoid tumor of the bladder arising beneath an inverted papilloma diagnosed by light microscopy and immunohistochemical studies. After the patient complained of hematuria and voiding difficulties, a polypoid mass was detected during cystoscopy and removed for examination. The distinctive histologic features of an inverted papilloma were readily identified. The characteristic pattern of a carcinoid tumor was confirmed with immunohistochemical studies. PMID- 8204020 TI - Salicylamides containing amino acid or pyran moieties with molluscicidal activity. AB - Salicylamide amino acid conjugates were prepared utilizing 5-formyl-, 5 dicyanoethenyl-, and 5-nitroethenylsalicylic acid. 5-Substituted salicylanilides were treated with glycine and formaldehyde in a Mannich type reaction affording the corresponding 3-(N-glycino)salicylanilides. The reactions of anilines with pyrans containing the salicylyl moiety yielded the corresponding salicylanilides. The obtained compounds were tested for molluscicidal activity. PMID- 8204021 TI - Synthesis of new 7-substituted 4-methylcoumarin derivatives of antimicrobial activity. AB - New cyclic derivatives derived from 4-methyl-7-coumarinyloxyacetic acid hydrazide have been synthesized. Some representative examples were screened for antimicrobial activity. PMID- 8204022 TI - Synthesis and anticancer activity of 2-substituted 2,3-dihydro-1,3,2- benzoxazaphosphorin-4-one and its 2-oxide derivatives. AB - As a result of the reaction of salicylic amide with PCl3 and POCl3 2-chloro-2,3 dihydro-1,3,2-benzoxazaphosphorin-4-one (1) and its 2-oxide 2 are obtained. Compounds 1 and 2 form amides with amines in 2-position. Antineoplastic action of the derivatives containing the bis(2-chloroethyl)amide group in 2-position was found. PMID- 8204023 TI - Acute toxic and teratogenic effects of cyclic imides in rodents. AB - Four structurally different cyclic imides or related derivatives (o-(N phthalimido)acetophenone (1), 2,3-dihydrophthalazine-1,4-dione (2), N-(4 methylphenyl)diphenamide (3), and 4,6-dihydro-5H-dibenz[c,e]azepine (4) were examined for acute toxicity in mice at multiple doses, for long term toxicity at a single dose in rats, and for deleterious effects on fertility and pup development in rodents. No deleterious effects were observed when mice were administered agents at 20, 50, and 100 mg/kg/day for seven days. All other measured characteristics and values were normal for the four compounds. The principle effect of the compounds was to reduce the percent pregnancies in treated mice compared to the controls. Compound 2 afforded the greatest reduction of pregnancy (54%) at 100 mg/kg/day. Compounds 3 and 4 caused a minor reduction in pregnancy (12-20%). The compounds did not appear to cause measureable teratogenic effects; pups of treated rodents thrived and survived as well as controls. There were no effects on murine male fertility when compounds were administered at 20, 50, and 100 mg/kg/day for six weeks. PMID- 8204024 TI - [Application of the rough sets theory to the analysis of structure-activity relationships of pyridinium antifungal compounds]. AB - Relationships between chemical structure and antifungal activity of 72 quaternary pyridinium chlorides were analysed using the method of rough sets. In the information system the compounds are described by eight condition attributes and divided into three classes of activity. Using the rough sets approach a smallest set of four condition attributes significant for a high quality of classification and accuracy of classes has been found. The resulting decision algorithm describes relations between structure and antifungal activity in terms of significant condition attributes. It may be helpful in predicting structures of new antifungal compounds to be synthesized. PMID- 8204025 TI - A khellin-like 7,7'-glycerol-bridged bischromone with anti-anaphylactic activity. AB - The synthesis of the title compound 3 is described. Its performance in Passive Cutaneous Anaphylaxis (PCA) testing was evaluated. PMID- 8204026 TI - [The pharmacokinetics of hypolipemic agents. 10. The dehalogenation of the hypolipemic agent ciprofibrate]. AB - rac-2 described as a metabolite of rac-1 was synthesized in four steps starting with rac-3. Partial dehalogenation occurs with LiAlH4. A new structure assignment of the resulting stereoisomers resulted from NMR spectroscopy. After oral administration of rac-1 in multiple dose studies to volunteers, rac-2 could not be detected within the limitations of sensitivity of HPLC (UV-detector) in plasma or in urine. PMID- 8204027 TI - [7-fluoro-4-chromone-3-sulfur compounds]. AB - The novel 7-fluoro-4-chromone-3-sulfur compounds 5-12 were synthesized from the sulfinic acid 4, which can be obtained from the enaminone 3 and thionyl chloride. Especially the Flosequinane-like sulfoxide 12 was prepared and the vasodilating activity was evaluated in isolated ring segments of rat aorta. PMID- 8204028 TI - Synthesis and antifungal activity of some 2-aryl-3-substituted 4-thiazolidinones. PMID- 8204029 TI - Threats to the scientific integrity of clinical trials. PMID- 8204030 TI - Physical examination and arteriography in patients with penetrating zone II neck wounds. AB - OBJECTIVE: To review the management of patients with penetrating zone II neck wounds to discern the value of physical examination and proximity arteriography for predicting arterial injury. DESIGN: A retrospective chart review of 178 patients treated for penetrating wounds to the neck. SETTING: A level I trauma facility in Dallas, Tex. PATIENTS: All patients seen from 1987 to 1991 with platysma penetration in zone II of the neck. INTERVENTION: Physical examination, arteriography, and surgical exploration were used to identify patients with arterial injuries in the neck after penetrating trauma. MAIN OUTCOME MEASURES: To identify the presence or absence of an arterial injury. RESULTS: Negative findings on physical examination ruled out an arterial injury in 99% of all patients. Patients with any sign of arterial injury had a 26% incidence of arterial injury confirmed at operation. Of 71 arteriograms in patients without signs or symptoms of arterial injury, only one had an arterial injury requiring operative intervention. CONCLUSIONS: Findings on physical examination are good predictors of arterial injury in patients with penetrating neck wounds and can exclude injury in over 99% of patients. Arteriography is a sensitive test but has a very low yield (1.4%). These findings question whether the current practice of mandatory neck exploration or proximity arteriography is necessary for patients without signs or symptoms of injury who have penetrating wounds of the neck. PMID- 8204031 TI - Salvage surgery for locally advanced and locally recurrent breast cancer. AB - OBJECTIVE: To determine if local control of breast cancer can be regained in patients with locally advanced and recurrent tumors using aggressive surgical treatment and reconstruction. DESIGN: A retrospective review of 15 consecutive patients. Patients were followed up from 8 to 32 months. SETTING: A university tertiary care facility in a metropolitan area. PATIENTS: All patients with locally advanced or recurrent breast cancer without known metastatic disease who underwent radical surgical resection of locally advanced breast cancer with reconstruction. MAIN OUTCOME MEASURES: Primary outcome measures were pathological findings, type of surgery, length of hospital stay, complications, local recurrence, and survival. RESULTS: Pathological findings showed 12 adenocarcinomas (80%) and three sarcomas (20%). Thirteen patients (86.7%) had undergone previous surgery, 11 (73.3%) had undergone previous radiation therapy, and all adenocarcinomas were progressing while patients were receiving chemotherapy. Full-thickness chest wall resection that included bone was required in 46.7%. The average hospital stay was 11.5 days. While 10 patients (66.7%) eventually manifested metastatic disease, local recurrence developed in only one. Minor complications occurred in six patients (40%) and major complications occurred in three (20%). There were no perioperative deaths. CONCLUSIONS: Patients presenting to our service had locally aggressive tumors that were recalcitrant to maximal medical management. With radical surgical treatment and reconstruction, there were no deaths, significant morbidity was low, and all but one patient regained local control. We found that aggressive surgical treatment and reconstruction is not only feasible in patients with locally advanced breast cancer but may be the only hope for local control in these patients who are difficult to treat. PMID- 8204032 TI - Axillofemoral grafting with externally supported polytetrafluoroethylene. AB - OBJECTIVE: To evaluate the results of axillofemoral bypass grafting using externally supported polytetrafluoroethylene. DESIGN: Consecutive patients who were operated on by us from 1983 to the present were prospectively followed up in a vascular registry. The results of surgery with respect to morbidity and mortality, patency, limb salvage, and patient survival were determined by life table methods. PATIENTS: A standardized operative technique was used to perform 184 axillofemoral bypass procedures in 164 consecutive patients (age range, 14 to 90 years; mean age, 67 years; female, 33%). Follow-up ranged from 0 to 95 months (mean, 23 months). RESULTS: Ischemia was the indication for 83% of the procedures, and aortic sepsis was the indication for 16%. There were nine operative deaths (5%) and 17 major complications. Life-table primary patency, limb salvage, and survival rates at 5 years were 71%, 92%, and 52%, respectively. Indication for surgery, patency of the superficial femoral artery, and the performance of multilevel procedures did not significantly influence patency. CONCLUSIONS: The results of axillofemoral grafting using polytetrafluoroethylene are equivalent to those achieved with other accepted methods of treatment for lower extremity ischemia, including balloon angioplasty, aortofemoral bypass, and infrainguinal bypass. Axillofemoral bypass is an appropriate technique that is deserving of more widespread use. PMID- 8204033 TI - The popliteal artery as inflow for distal bypass grafting. AB - OBJECTIVE: To examine the patency and limb salvage characteristics of the popliteal-distal artery saphenous-vein bypass in patients with minimal superficial femoral artery disease. DESIGN: A retrospective review. SETTING: A tertiary care university hospital in the Chicago, Ill, metropolitan area. PATIENTS: Fifty-two popliteal-distal artery saphenous-vein bypasses for occlusive disease were performed in 51 patients between 1980 and 1993. The mean age at operation was 62 years (range, 37 to 85 years); 34 patients (67%) were male, 45 (88%) were smokers, 44 (86%) had diabetes, and 34 (67%) had coronary disease. The primary indications for operation were gangrene (21 patients [41%]), ulcer (15 patients [29%]), and rest pain (16 patients [31%]). INTERVENTION: Bypass of diseased arterial segments was performed using popliteal-distal artery saphenous vein bypass grafts. The proximal anastomoses were either to the above-knee popliteal artery (50%) or to the below-knee artery (50%), with outflow to tibial (79%) or pedal vessels (21%). MAIN OUTCOME MEASURES: Overall patient survival, limb salvage, and primary and secondary graft patency. RESULTS: Follow-up of graft patency ranged from 1 day to 11 years (mean follow-up, 2.7 years). The perioperative mortality was 2% and life-table survival was 94% at 1 year, 68% at 5 years, and 50% at 10 years. Primary patency was 90% at 1 month, 82% at 1 year, and 75% at 5 years. There were 14 primary graft failures, only two of which could be traced to progression of proximal disease; five failures occurred less than 30 days after operation. Six of these 14 patients contributed to secondary patency that was 96% at 1 month, 90% at 1 year, and 79% at 5 years. Limb salvage was 96% at 1 month, 90% at 1 year, and 87% at 5 years (seven major amputations were required). No significant differences in patency, limb salvage, or survival were observed on comparison of the level of the proximal or distal anastomosis, type of vein graft, or presence of comorbidities. CONCLUSIONS: We conclude that popliteal-distal artery bypass provides excellent patency and limb salvage for patients with severe ischemia. The use of a popliteal artery inflow source is preferable in patients with a paucity of venous segments since progression of proximal disease rarely leads to graft failure. PMID- 8204034 TI - Acute aortic occlusion. A 40-year experience. AB - OBJECTIVE: To review a large experience with acute aortic occlusion (AAO) to better define the cause, clinical presentation, treatment, prognostic variables, and outcome. DESIGN: Retrospective review of 46 consecutive patients with AAO during a 40-year period. SETTING: A large urban tertiary care referral center in Detroit, Mich. PATIENTS: Adult patients with arteriographic and/or operative confirmation of acute occlusion of the abdominal aorta plus signs and symptoms of acute ischemia. INTERVENTION: Operative and nonoperative treatment of AAO. MAIN OUTCOME MEASURES: Mortality, morbidity, and long-term survival. Other variables measured included cause, risk factors, and effects of duration and severity of ischemia and treatment methods on outcome. RESULTS: Two primary causes were identified--embolism (65%) and thrombosis (35%). Heart disease and female gender were risk factors for embolism, while smoking and diabetes were risk factors for thrombosis. Severity of ischemia on presentation correlated better with outcome than duration of ischemia. The hospital mortality rate was 35% and morbidity, 74%, with no difference between the two groups. Recurrent arterial embolism occurred in 43% of patients with embolic AAO. Seventy-two percent of AAO survivors were alive 5 years after therapy. CONCLUSIONS: Acute aortic occlusion remains a serious vascular surgical emergency with significant morbidity and mortality, even when recognized promptly and treated appropriately. Nevertheless, survivors have a reasonable long-term outcome. Permanent anticoagulation is suggested in patients with embolic AAO to minimize a high incidence of recurrent arterial embolism. PMID- 8204035 TI - Is Barrett's metaplasia the source of adenocarcinomas of the cardia? AB - OBJECTIVE: To investigate the prevalence of Barrett's esophagus in patients with adenocarcinomas located at the gastroesophageal junction. DESIGN: A case series of patients who underwent esophagogastrectomy for adenocarcinoma was retrospectively reviewed. Tumors were grouped by location as esophageal, cardiac, and subcardiac, and the prevalence of specialized intestinal metaplasia in the histological specimens was determined. SETTING: A university department of surgery that specializes in esophageal diseases. PATIENTS: One hundred patients with adenocarcinoma of the esophagus, cardia, or proximal stomach. MAIN OUTCOME: Cardiac adenocarcinomas were associated with Barrett's esophagus in 42% of the patients. RESULTS: Specialized intestinal metaplasia was identified in the histological sections from the resected specimen in 42% (13/31) of cardiac adenocarcinomas and in 79% (38/48) of esophageal adenocarcinomas but in only 5% (1/21) of subcardiac adenocarcinomas. The preoperative endoscopic biopsy results concurred with the final diagnosis of Barrett's esophagus in 33 of the 38 esophageal tumors, six of the 13 cardiac tumors, and the one subcardiac tumor but failed to detect specialized intestinal metaplasia in 54% (7/13) of cardiac tumors. Cardiac tumors were associated with shorter lengths of Barrett's mucosa than esophageal tumors (2.7 +/- 1.8 cm vs 7.4 +/- 3.4 cm, P < .01). The Barrett's metaplasia was dysplastic in 36 of the 38 esophageal tumors, 10 of the 13 cardiac tumors, but not in the subcardiac tumor. CONCLUSIONS: Adenocarcinomas located at the gastroesophageal junction were associated with Barrett's metaplasia in nearly one half of the patients. The length of the Barrett segment tends to be short and may be missed during endoscopy. The presence of high-grade dysplasia within Barrett's mucosa supports a barrett's origin for half of the adenocarcinomas arising at this location. PMID- 8204036 TI - Gastric remnant cancer has a better prognosis than primary gastric cancer. AB - OBJECTIVE: To study the prognosis of gastric remnant cancer following radical resection (group 1) compared with that of primary gastric cancer of the upper third of the stomach following radical resection (group 2). DESIGN: Cohort study with a 5-year follow-up. SETTING: A university hospital in Austria. PATIENTS: Group 1 consisted of 43 patients, and group 2, of 61. Postoperative deaths and deaths during the follow-up period that were not related to gastric cancer were excluded. Fifteen patients in group 1 (34.9%) presented with stage I cancer; 10 (23.3%), stage II; 13 (30.2%), stage III; and five (11.6%), stage IV. Twenty patients in group 2 (32.8%) presented with stage I cancer; 12 (19.7%), stage II; 15 (24.6%), stage III; and 14 (22.9%), stage IV (Union Internationale Contre le Cancer staging classification, 1987). MAIN OUTCOME MEASURES: Overall and stage related 5-year survival rates. RESULTS: The overall 5-year survival rate was 53.5% in group 1 and 32.8% in group 2 (P < .05). The stage-related 5-year survival rate in group 1 was 100% for stage I and 80% for stage II. In group 2, the stage-related 5-year survival rate was 65% for stage I and 25% for stage II (both, P < .01). No significant difference was noted for stages III and IV. CONCLUSIONS: The prognosis of cancer of the gastric remnant presenting as stage I or II is good and is significantly better than that of the equivalent stages of primary cancer of the upper third of the stomach. PMID- 8204037 TI - In situ and surface liver cooling with prolonged inflow occlusion during hepatectomy in patients with chronic liver disease. AB - OBJECTIVE: We examined in situ and surface liver hypothermia with continuous and prolonged inflow occlusion during hepatic resection (segmentectomy or subsegmentectomy). PARTICIPANTS: Eight patients with cirrhosis and three with chronic hepatitis. METHODS: In situ chilling was achieved by introducing cold Ringer's lactate solution through the portal vein, under conditions of portal triad occlusion. RESULTS: The liver tissue temperature fell to a mean of 28.4 degrees C 5 minutes later. The time of ischemia ranged from 32 to 52 minutes (mean +/- SD, 47.8 +/- 5.6 minutes). The mean blood loss was significantly lower than in our conventional hepatectomy series (680 vs 1520 mL, P < .02). MAIN OUTCOME: There were no serious complications, and hypoxia-induced liver injury was ameliorated, as shown by liver function tests. CONCLUSION: Hepatectomy with prolonged inflow occlusion is justified in low-risk patients with chronic liver disease if it is combined with liver hypothermia, such as simple in situ and surface cooling. PMID- 8204038 TI - Transthoracic endoscopic sympathectomy in the treatment of palmar hyperhidrosis. AB - OBJECTIVE: Transthoracic endoscopic electrocauterization of the sympathetic chain for palmar hyperhidrosis is presented. DESIGN: A retrospective study of 180 patients during a 2-year period was carried out. The duration of follow-up was from 2 to 12 months. SETTING: General community, referral center, and hospitalized care. PATIENTS: This study was carried out in 180 patients (116 female and 64 male). The age distribution was between 13 and 43 years (mean age, 21.6 years). They complained of palmar hyperhidrosis without other underlying diseases. INTERVENTIONS: One-stage bilateral surgery except for three patients with unilateral pleural adhesions. MAIN OUTCOME MEASURES: Patients were interviewed 1 week after surgery and then they were contacted by a questionnaire about improvement of hyperhidrosis and complications. RESULTS: This procedure shows a success rate in 98% of the patients. No pneumothorax requiring a chest tube drainage and no Horner's syndrome were recorded. The most common side effect was compensatory sweating in 70% of these patients. CONCLUSION: This procedure is effective, simple, and requires only an overnight study. It is recommended as the method of choice for surgical treatment of upper extremity hyperhidrosis. PMID- 8204039 TI - Pancreatic cancer. Cytologic study of peritoneal washings. AB - OBJECTIVE: To delineate the frequency and significance of free cancer cells in the peritoneal cavity of patients with pancreatic exocrine adenocarcinoma. DESIGN: Randomly selected patients with pancreatic cancer had peritoneal washings performed at the beginning and conclusion of laparotomy. Results of cytologic studies were correlated with the clinical findings, size, spread, and resectability of the tumor and with the survival time of the patient. All patients were followed up until the present or until their deaths. SETTING: Tertiary care, referral hospitals in Toledo, Ohio. PATIENTS: Only patients with biopsy-proven adenocarcinoma of the pancreas were included. Thirty-six patients, yielding 62 specimens for cytologic study, were included. INTERVENTION: Peritoneal washings were performed at the beginning and completion of laparotomy. Each washing was evaluated independently by two skilled cytologists. If present, ascites was quantitated and studied cytologically. Biopsy specimens were obtained in each patient at the time of the study. MAIN OUTCOME MEASUREMENTS: Presence or absence of malignant cells in peritoneal fluid; maximal diameter, grade, and spread of cancer; presence and volume of ascitic fluid; resectability of cancer; and length of survival of the patient. RESULT: Of the 36 patients studied, three had positive cytologic findings. All three had peritoneal carcinomatosis. Of 11 patients with ascites, only one had positive cytologic findings. CONCLUSIONS: Results of cytologic studies of peritoneal washings or of ascitic fluid are seldom positive with pancreatic exocrine carcinoma. When positive, they denote a very grave prognosis. PMID- 8204040 TI - Roentgenographic evaluation of the cervical spine. A selective approach. AB - BACKGROUND: To determine if routine radiographic evaluation of the cervical spine could be eliminated in the alert, sober trauma patient who has no neck pain, tenderness, or other major injuries without a significant increase in missed occult injury. DESIGN: Prospective cohort study. SETTING: Emergency department and general surgery service at a military tertiary medical center. MAIN OUTCOME MEASURE: Those patients with cervical spine injuries. RESULTS: Sixteen patients (2%) had cervical spine injuries, all had signs and/or symptoms of their injury on presentation. Ninety-six patients (14%) who were not intoxicated and had no neck pain, tenderness, or other major injuries were evaluated. None of these patients had abnormal cervical spine studies. Two hundred ninety patients (43%) were followed up between 30 to 150 days. No missed injuries were noted. CONCLUSIONS: These results indicate that blunt trauma patients may not require cervical spine roentgenography if they meet the following criteria: absence of mental status changes, intoxication, neck pain or tenderness, neurologic signs or symptoms, or simultaneous major distracting injury. Because of the small incidence of cervical spine injuries, further studies are necessary to evaluate the positive predictive value of history and physical examination of the cervical spine in a trauma patient. PMID- 8204041 TI - Carotid endarterectomy with primary closure does not adversely affect the rate of recurrent stenosis. AB - OBJECTIVES: To review our results with carotid endarterectomy using primary closure and to study the incidence of true recurrence in this group of patients. A secondary objective was to review the effect of risk factors on recurrence of stenosis following carotid endarterectomy. DESIGN: Cohort study. SETTING: University hospital. PATIENTS: Over 3 years, 232 patients underwent 268 endarterectomies. INDICATIONS: Transient ischemic attacks developed in 119 patients, asymptomatic stenosis in 108 patients, and stroke in 41 patients. One hundred fifty-seven patients (184 operations) qualified for late analysis by completing all aspects of follow-up. OUTCOME MEASURES: Serial duplex scans recorded stenosis (> 50% diameter reduction). Clinical evaluation identified transient ischemic attacks and stroke. RESULTS: Overall, 12 recurrent stenoses developed in the 184 patients available for study during a follow-up of 24 months (6.5% incidence of late stenosis). Of these 12 patients, only eight had either a normal completion angiogram or a normal carotid duplex scan within 3 months of surgery, thus qualifying for analysis as having developed true recurrent stenosis. True recurrent stenosis occurred in eight (4.3%) of 184 patients. Risk factor analysis did not reveal a statistically significant impact on recurrent stenosis, but several trends were identified. Gender and consumption of tobacco may predispose toward the development of recurrent stenosis. CONCLUSION: Recurrent stenosis is sufficiently uncommon following primary closure to justify continued use of this technique. Patch angioplasty may be considered in women and smokers. PMID- 8204043 TI - Ileal duplications in adults. Presentation and treatment. AB - Alimentary tract duplications are uncommon anomalies that usually present in childhood. They are most common in the ileum but can occur anywhere along the alimentary tract. In this report, we describe an adult with an ileal duplication and review 12 other reported cases of ileal duplication in adults. Abdominal pain, nausea and/or vomiting, weight loss, and hematochezia were the most common symptoms. No patient was correctly diagnosed before operation. Three patients had malignant neoplasm in the resected specimens. Resection of the duplication and adjacent bowel is recommended because of the common blood supply to both, the possibility of malignant degeneration, and the risk of gastrointestinal ulceration and hemorrhage from ectopic gastric mucosa. PMID- 8204042 TI - Pancreatic pseudocyst resolution after parathyroidectomy for hyperparathyroidism. AB - Hyperparathyroidism is a rare cause of pancreatic inflammatory disease. Appropriate treatment of coexistent hyperparathyroidism and pancreatitis, especially when complicated by pseudocyst formation, is unsettled. We describe two patients with primary hyperparathyroidism who developed pancreatitis associated with multiple pseudocysts. The largest cyst in each patient was 9 and 5 cm, respectively. After correction of hyperparathyroidism and normalization of serum calcium levels by removal of a parathyroid adenoma, the pseudocysts resolved in both patients, as documented with computed tomography. We conclude that uncomplicated pancreatic pseudocysts in patients with primary hyperparathyroidism can be treated expectantly. Surgical correction of hyperparathyroidism and normalization of serum calcium levels should precede pancreatic intervention when possible, since pseudocyst resolution is likely and the risks of postoperative hypercalcemia are avoided. PMID- 8204044 TI - William Tod Helmuth and Andrew Jackson Howe. Surgical sectarianism in 19th century America. AB - Nineteenth-Century American society was particularly prone to the establishment of numerous unorthodox medical practices and their alternative therapies. The most influential of the unorthodox medical groups were the homeopathic and eclectic sects. From within the ranks of homeopathy and eclecticism, William Tod Helmuth and Andrew Jackson Howe, respectively, emerged to become the best-known sectarian surgeons of their era. Through a review of their lives this forgotten chapter in the history of American surgery is recollected. PMID- 8204045 TI - The success of duplex ultrasonographic scanning in the diagnosis of extremity vascular proximity trauma. PMID- 8204046 TI - [Dissector, pathologist, clinical pathologist]. PMID- 8204047 TI - [Morphologic classification of glomerulonephritis revisited]. AB - The use of a wide spectrum of monoclonal antibodies allowed us to distinguish two groups of glomerulopathies: inflammatory (glomerulonephritis) and non inflammatory. Glomerulus infiltration with inflammatory cells, glomerulus cell proliferation, heterogeneous composition and localization of the immune complex depositions even within one morphological form are characteristic of inflammatory glomerulopathies. A proliferative reaction is practically absent in non inflammatory glomerulopathies, localization and deposits composition within one morphological form is homogeneous, the appearance of non-immune deposits containing only fibrin or low-density lipoproteins is typical. Specific podocyte marker, antigen of acute lymphoblastic leukemia, is practically absent at early stages of non-inflammatory glomerulopathies. PMID- 8204048 TI - [Teseus phenomenon: a new symptom]. AB - Morphological proof of a new phenomenon is presented: moderately activated phagocyte (alveolar macrophage, neutrophil leucocyte) remains connected with a site of its movement by a thin thread. The latter represents a thin tube consisting of sarcolemma substance and contains retractile elements. Thread-like structure gives the phagocyting cell the possibility to return and to reach the major routes of the host--this is a way by which the normal tissue is cleaned up under conditions close to the physiological norm. The phenomenon reminds method used by Teseus for searching exit from the labyrinth after his victory over Minotaurus. PMID- 8204049 TI - [Chronic course of influenza with extrapulmonary involvement]. AB - Results of the investigation of 265 placentas and 387 necropsies with the use of a wide spectrum of morphological, immunological and virological methods are presented. The existence of extrapulmonary damages, those of placenta (50 observations) and brain (17 observations), is shown. The variants of the influenza infection (persisting, chronic and manifesting) are discussed. The possibilities of a long-term survival of the infectious agent in the long-living brain and placental structures are considered. The proofs are presented showing the secretion by these organs of local factors of non-specific defense such as interferon. PMID- 8204050 TI - [Alcoholic disease]. AB - A new concept of alcoholic disease has been developed on the basis of the study of 355 corpses of persons abusing ethanol and 335 white male rats with experimental alcoholic intoxication. A new nosological entity "alcoholic disease" (AD) is suggested instead of "chronic alcoholism". Pathogenesis of AD consists of 3 stages: I--repeated acute alcoholic intoxication, II--drunkenness, III- alcoholism and its complications. The definition of AD is given. A leading role in it belongs to the damage of the liver, heart, lungs and brain. The stage 1 involves degenerative changes in the organs, stage II--spectrum of the damage is larger but the changes are still reversible. The patients are treated in hospitals where the role of ethanol in the heart and liver damage is not taken into consideration. Stage III--irreversible changes. Hence, the diagnosis and treatment of stage II is necessary as it is curable. PMID- 8204051 TI - [Neuroendocrine stomach carcinoma]. AB - Morphology of the neuroendocrine stomach tumours, including carcinoid tumours (CT) and so-called carcinoids of complex structure is studied (189 tumours of patients operated in the Institute), 164 tumours are studied using routine histological methods including Grimelius methods. Immunophenotyping with the use of antibodies to VIII type keratin, carcinoembryonic antigen, meconial intestinal antigen B1MA, Factor VIII, IV-type collagen and laminin were performed in 25 cases. Neuroendocrine carcinomas represented a group of 86 tumours (45.5%), 28 (14.4%) of them were carcinoid tumours and 58 (30.7%)--complex carcinoids. Among CT, moderately differentiated tumours predominated (18), 4 tumours were poorly differentiated and there was a combination of structures in 6 tumours. The conclusion is made that neuroendocrine stomach carcinomas are epithelial tumours with a complex functional differentiation manifesting in different types of secretion: neuroendocrine and non-endocrine characteristic of stomach epithelium. PMID- 8204052 TI - [Importance of autopsy in present-day conditions]. PMID- 8204054 TI - [Anatolii Vladimirovich Smol'iannikov]. PMID- 8204053 TI - [Glial fibrillar acidic protein in peripheral nerve tumors in rats]. AB - Twenty-seven peripheral nerve tumours of BD VI rats from the histological archives of the International Agency for Research on Cancer were immunohistochemically studied for GFAP reactivity. Twelve tumours were induced by nitrosoethylurea (NEU) and 13 tumours were spontaneous. Thirteen tumours (7 of them NEU-induced and 6 spontaneous) revealed GFAP-reactivity which was relatively high (large areas of GFAP-positive cells) in 4 neoplasms (3 induced and 1 spontaneous). GFAP-positive tumours were not histologically distinguishable from GFAP-negative tumours. GFAP-positive tumours were also positive for S-100 protein although the incidence and the intensity of GFAP-reactivity were much lower than that of S-100 reactivity. Early NEU-induced schwannomas were negative for GFAP and S-100; all GFAP-and S-100-positive tumours were large neoplasms with an invasive growth. GFAP-positivity was observed in both solid and cystic schwannomas. The results of the study represent the additional data on the observation of GFAP outside of the central nervous system. PMID- 8204055 TI - [Manifestations of blood vessel growth in embryogenesis and reparative regeneration]. AB - Four types of blood vessel growths are established: a) autochtonous linked with the formation of protocapillaries from vasoformative mesenchymal cells; 2) loop like, characterized by a vascular loop proliferation (loop from loop mechanism); c) formation of single vessels from separated growth cambial elements resulting in the link of two functioning vascular ferminals (microvessel from microvessel mechanism); d) formation of vessels-satellites associated with the anastomosis between growth germs with the microvessels from which they are being separated. All the above types of vasculogenesis are manifested in the prenatal ontogenesis, while in reparative regeneration two last types only. Sources of endothelial germ formation are described, the dynamics of transformation of newly formed capillaries into the arterioles and venules, arteries and veins are studied, materials on the reparative vasculogenesis pathology are presented. PMID- 8204056 TI - [Intrauterine mycoplasmosis in late miscarriage]. AB - 118 late abortions were investigated at week 18-28 of pregnancy with the use of light and immunofluorescent microscopy. Intrauterine infections were found in 86 cases including 44 observations of mycoplasmosis, 16-M. hominis, 18-M. pneumoniae, 10-U. urealyticum. Histologically similar changes were found in the form of vacuolar degeneration of the amnion, trophoblast of the basal lamina and foetal coats, inner foetal organs and neuroepithelial cells in the central nervous system. Apart from this, focal leucocytic-lymphocytic infiltration was observed. Marked myeloid hematopoiesis was found in the liver. Maximum changes were found in the placenta and foetal organs in chronic placental deficiency. PMID- 8204057 TI - [Macrophage ultrastructure in the focus of experimental inflammation in genetically diabetic mice]. AB - Mice of the strain C57BL/KsJ db+/db+ with a genetically predetermined diabetes mellitus type II were used. Experimental inflammation was produced by a subcutaneous administration of celloidin globules. Less developed synthetic and secretory apparatus and a decrease of cytoplasmic microprocesses formation are observed in the macrophages at both early (1 day) and late (14 days) periods in the diabetic animals. Besides that, less total size of the lysosomal apparatus at early periods and overloading of the cytoplasm with a non-degraded phagocytized material at late periods are observed in diabetic mice. This is considered as a morphological basis of the mononuclear phagocyte function decrease in diabetes mellitus. PMID- 8204058 TI - [Effect of constant electric current on energy metabolism and ultrastructure of the isolated rat heart in the course of its post-ischemic reperfusion]. AB - It is established, using Langendorff's perfusion method, that the constant current improves the energetic metabolism of the isolated heart during its reoxygenation. The constant current increases the intensity of the succinate oxidation, exerts a membrane stabilizing effect on the cardiomyocytes, stimulates intracellular reparative processes in the damaged myocardium. PMID- 8204059 TI - [Twenty-five clinical-anatomic conferences of pathology departments of the clinics and I. M. Sechenov chair in 1986-1989 (protocols of conferences No. 328 357)]. PMID- 8204060 TI - [Isolated amyloidosis of the islands of Langerhans and diabetic mellitus]. AB - One observation of isolated amyloidosis of the insular apparatus of the pancreas followed by the development of diabetes mellitus and diabetic microangiopathy in various organs is described. Total amyloid involvement of all insular apparatus is pointed out. PMID- 8204061 TI - [Pathologic diagnostic criteria of cardiomyopathy in children]. AB - Pathologic diagnostic criteria of the hypertrophic and dilated cardiomyopathy and comparative histologic characteristics of chronic non-specific myocarditis and restrictive cardiomyopathy are presented. The basis of the idiopathic cardiomyopathies is according to the authors, destructive and degenerative processes in cardiomyocytes, their combination with a zonal-segmentary muscle hypertrophy, dilatation and myocardium sclerosis. Dependence of the cardiomyopathy upon the mitochondrial dysfunction and the aggravation of morphological changes by viruses is emphasized. PMID- 8204062 TI - [A case of unusual sphingomyelinosis]. AB - Sphingomyelinosis in a 1.5-year-old girl with unusual clinicomorphological manifestations without hepato- and splenomegaly is described. The diagnosis was established on the basis of postmortem biochemical examination of the brain. PMID- 8204063 TI - [A case of a vascular form of pulmonary hypertension simulating Ayerza's disease]. AB - In observation of a rare disease that developed in a young man of 24 there was a thromboembolism of the pulmonary artery branches from the profound veins of the shank with their subsequent recalibration. Thus there was in this case a vascular form of pulmonary hypertension simulating Ayerza's disease. PMID- 8204064 TI - [Past and present-day aspects of biopsy examination]. PMID- 8204065 TI - [Usefulness of ambulatory monitoring of blood pressure in the evaluation of hypertensive subjects]. PMID- 8204066 TI - [Nonpharmacological therapy of tachycardiac syndromes--where are we?]. PMID- 8204067 TI - [Influence of cardiac perfusion on relations of pressure/volume of the left ventricle]. AB - PURPOSE: To analyze the influence of the myocardial engorgement due to coronary perfusion on the left ventricular diastolic pressure/volume (P/V) relations. METHODS: The study was undertaken in the isovolumic blood-perfused dog heart preparation (n = 7). The P/V relations were determined promoting ventricular volumes variations by steps of 2ml, in two conditions: during coronary perfusion pressure of 100mmHg and after occlusion of the perfusion line. RESULTS: It was verified that the P/V relations obtained without myocardial perfusion shifted to the down right in respect to the perfused heart. A exponential fitting of the P/V relations allows to conclude that there was no difference among the slopes of the curves obtained with and without perfusion. CONCLUSION: Our results indicated that coronary perfusion restrain the capacity of the left ventricle to receive blood, but there is no influence on the passive elastic stiffness of the chamber. This effect was taught to be consequence of the myocardial erectile property. PMID- 8204068 TI - [Early revascularization of the arteries not related to infarction improves regional and global function of the left ventricle after acute myocardial infarction]. AB - PURPOSE: To evaluate if early interventions which increase flow in the non infarct related arteries (NRA) could improve long-term ventricular function in the non-infarct (NI) area after an acute myocardial infarction (MI). METHODS: We studied regional wall motion analyzed by the center-line method in two groups of patients with significant stenoses (> or = 70%) in the NRA after successful coronary reperfusion (chemical or mechanical thrombolysis). Group I (GI) consisted of 21 patients that were submitted to early (mean 14 days) complete surgical revascularization of both NRA and infarct related artery (IRA); the 12 group II (GII) patients underwent successful revascularization of the IRA only, with percutaneous transluminal coronary angioplasty (mean 6 days). Paired ventriculograms were obtained within 48 hours of the infarction and a mean of 17 months later. RESULTS: NI area contractility in GI patients improved from -0.35 +/- 2.16 to +0.62 +/- 1.6sd/chord (p < 0.05), whereas in GII decreased from +0.54 +/- 1.78 to -0.66 +/- 1.72 sd/chord (p < 0.05), p < 0.05 between the groups at follow-up. Mean infarct area wall motion did not differ between the two groups: from -3.04 +/- 2.43 to 2.61 +/- 2.49 sd/chord in GI (p = NS), and from -2.68 +/- 2.54 to -2.93 +/- 2.35 sd/chord in GII (p = NS). Mean global left ventricular (LV) ejection fraction did not change in GII patients (0.72 +/- 0.09 and 0.67 +/- 0.12, p = NS), but significantly increased from 0.63 +/- 0.12 to 0.72 +/- 0.11 in GI patients (p < 0.01). CONCLUSION: These data suggest that early revascularization of NRA with significant stenoses can improve not only the NI area regional contractility, but also the global LV function in the long-term follow-up of post MI patients treated with thrombolytic therapy. PMID- 8204069 TI - [Daily and weekly circadian variations in sudden death in Chagas disease]. AB - PURPOSE: To determinate the circadian daily and weekly variations in the incidence of sudden death due to Chagas' disease. METHODS: In 50 chronic chagasic individuals with sudden death due to Chagas' disease and in 473 individuals with natural, not sudden death, we analyzed both the day of the week and the time of the death. Statistical tests were applied to determine the significance of the difference between proportions and averages. RESULTS: For the chagasic group the values indicated a highly significant excess of lethality for the period between 12 and 6pm. The occurrence of the sudden death was the same in the different days of the week for both groups. CONCLUSION: The observed results suggest that the sudden death associated with Chagas' disease has a circadian pattern with a vespertine peak. Weekly variations in the sudden death of chronic chagasic individuals were not detected. PMID- 8204070 TI - [Neurological events in infective endocarditis]. AB - PURPOSE: The study of frequency, modalities and course of neurological complications of infective endocarditis (IE), as well as the current indication and value of supplementary examinations. METHODS: Sixty-three patients with IE, 39 with native valve and 24 with valvar prosthesis, were prospectively studied; the mean age was 42 years and 45 (71.4%) were males. Two groups were formed: A) 41 patients without neurological events and B) 22 patients who presented 28 neurological events before or during hospitalization: ischemic cerebrovascular accident 20, hemorrhagic cerebrovascular accident 2, meningeal hemorrhage 2, meningitis 2, brain abscess 1 and seizure 1. All patients were submitted to neurological clinical examination; 57 computerized tomographies of the cranium, 28 arteriographies and 32 cerebrospinal fluid analysis were performed. RESULTS: The incidence of neurological events corresponded to 34.92% of IE patients, with a clear predominance (85.71%) of vascular as compared to infectious manifestations. Mortality was 2.32 times higher in group B patients (22.73% x 9.76%), albeit p = 0.256, and was not related to staphylococcal etiology. The neurological events were not related to sex, age and presence of valvar prosthesis. The presence of neurological complications was greater (p = 0.047) in patients with simultaneous infections in two valves (mitral and aortic) and also (p = 0.00884) in those with IE in prosthesis implanted for less than three months. All supplementary neurological examinations in group A were normal. CONCLUSION: 1) Occurrence of neurological events is a factor which influences the prognosis of IE; 2) supplementary neurological examinations did not reveal subclinical neurological complications; 3) neurological complications were significantly more frequent in patients with simultaneous mitral and aortic valve IE; 4) IE in prosthesis implanted for less than 3 months has a greater probability to develop a neurological picture as compared to IE in prosthesis implanted for more than 3 months. PMID- 8204071 TI - [Radiofrequency ablation of incessant supraventricular tachycardia due to anomalous pathway of retrograde decremental conduction]. AB - Woman, 46 years-old with incessant supraventricular tachycardia and tachycardiomyopathy. The diagnosis of a concealed retrograde long conduction time accessory pathway was obtained with the delay of the next atrial activation by delivering a ventricular premature beat during His bundle refratoriness. During electrophysiologic investigation the earliest atrial activation was found to be within the coronary sinus ostium. Two 25 watts applications of radiofrequency were followed by the interruption of the incessant supraventricular tachycardia. The patient has remained symptom free without recurrence for 60 days. Radiofrequency was effective for the treatment of this tachycardia. PMID- 8204072 TI - [Anticoagulation in heart diseases]. PMID- 8204073 TI - [Ambulatory monitoring of blood pressure]. PMID- 8204074 TI - [Multicenter comparative study of the effects of benazepril and captopril in mild and moderate systemic hypertension]. AB - PURPOSE: To evaluate the efficacy and safety of benazepril versus captopril in patients with mild or moderate systemic arterial hypertension (SAH). METHODS: A multicenter, double-blind, randomized trial analyzed 174 patients, mean age of 52 +/- 9 years, 68 (39%) men. After 2 weeks under placebo, 90 patients were treated, during 6 weeks, with 10 mg, once a day, of benazepril (BZ) and 50 mg, twice a day, of captopril (CPT). At week 3, 25 mg of hydrochlorothiazide (HCT) was added if diastolic blood pressure (DBP) was greater than 90 mmHg. Side effects were analyzed as a not related, unlikely, possible, probable and definitive regard to treatment. RESULTS: Systolic (p < 0.001) and DBP (p < 0.0001) reductions were observed in both groups. Additional reduction was observed in both groups when 25 mg of HCT was added in patients with DBP > 90 mmHg at week 3. Heart rate was unchanged. The response to treatment was better at BZ group (74% versus 59% of good and excellent response; p = 0.037). Side effects classified as probable or definitive in relation to the treatment occur in 3 (3%) and 10 (11%), respectively at BZ an CPT groups. Laboratorial changes were not observed during treatment. CONCLUSION: BZ (10 mg) was superior to CPT (50 mg) in patients with discrete and moderate SAH. PMID- 8204075 TI - [Submitral left ventricular aneurysm in a Brazilian Indian]. PMID- 8204076 TI - Post-training intrahippocampal infusion of protein kinase C inhibitors causes amnesia in rats. AB - This experiment investigated the effect on memory, in rats, of the bilateral intrahippocampal post-training infusion of two different inhibitors of protein kinase C activity, staurosporin and CGP41231. Male Wistar rats were implanted bilaterally with cannulae aimed at the CA1 region of the dorsal hippocampus. After recovery from surgery, they were trained in step-down inhibitory avoidance using a 0.5-mA footshock and tested for retention 24 h later. Immediately or 30, 120, or 180 min after training they received, through the cannulae, infusions of vehicle, staurosporin (1.0 microgram), or CGP41231 (2.5 micrograms). The two drugs caused full retrograde amnesia when given immediately or 30 min post training, partial amnesia when given 120 min after training, and had no effect when given 180 min after training. The results support the suggestion that memory involves long-term potentiation initiated at the time of training in the hippocampus. Inhibitors of protein kinase C block the development of long-term potentiation when administered in the first 2 h after induction. PMID- 8204077 TI - Multivariate analysis of behavioral aging highlights some unexpected features of complex systems organization. AB - Ten different behavioral tests were performed on a population of young (n = 20) and aged (n = 20) Fischer 344 rats. The relationship structure among these tests was studied by principal component analysis applied both to the entire data set and separately to the two age groups. This analysis proved very useful in highlighting a global index of the rat "behavioral" age based on the entire test set. The analysis effected separately on the two age groups evidenced qualitative differences between them that were linked to the different meaning the same test would assume in rats of different ages. From an overall methodological viewpoint, this work indicates that the correlations among behavioral parameters appear to depend on the observational scale and that the spin-glass model represents an appropriate metaphor to approach the study of the correlations in biological systems. PMID- 8204078 TI - Memory for spatial location as a function of temporal lag in rats: role of hippocampus and medial prefrontal cortex. AB - Rats with medial prefrontal cortex, hippocampus, or cortical control lesions were tested on an eight-arm radial maze task, in order to examine memory for the temporal order of spatial locations as a function of temporal lag. During the study phase of each trial, rats were allowed to visit each of eight arms once in an order that was randomly selected for that trial. The test phase required the rats to choose which of two arms occurred earlier in the sequence of arms visited during the study phase. The arms selected as test arms varied according to temporal lag (0-6) or the number of arms that occurred between the two test arms in the study phase. The control rats performed at chance at a temporal lag of zero, but their performance was above chance for the remaining lags, improving after the temporal lag exceeded zero. The hippocampal-lesioned rats showed a marked deficit, performing at chance for all lags, with some savings for those items occurring at the end of the list. The medial prefrontal cortex-lesioned rats showed a less severe deficit. The results of these data support the notion that both the hippocampus and the medial prefrontal cortex play significant roles in memory for the temporal order of spatial locations. PMID- 8204079 TI - Training in a novel environment improves the appetitive learning performance of the snail, Lymnaea stagnalis. AB - The effect of novelty, an environmental background variable affecting feeding and appetitive learning performance, was examined in a behavioral study of the pond snail Lymnaea stagnalis. Transfer of snails into a novel aquatic environment (clean water) evoked exploratory behavior which manifested itself in an increased number of spontaneous rasping movements of the mouth over the second to fifth minute after exposure to the novel environment. The intensity of this behavior was much weaker in a familiar environment (used water from the home tank). Similarly, sucrose-induced feeding rates were highest when the snails were given the sucrose stimulus in a novel environment. The effectiveness of appetitive conditioning using tactile stimulus paired with food (Kemenes & Benjamin, 1989a) improved when the snails were subjected to conditioning in a novel environment. Satiety, an internal variable, suppressed the stimulating effects of the novel environment on the spontaneous, unconditioned, and conditioned feeding alike. After training in the novel environment, the conditioned response was retained for up to 12 days and thus provided a robust behavioral paradigm for the extension of the analysis to the neurophysiological mechanisms of factors affecting appetitive learning in molluscs. PMID- 8204080 TI - Interaction of GABAergic and beta-noradrenergic drugs in the regulation of memory storage. AB - These experiments examined the interaction of drugs affecting noradrenergic and GABAergic systems, administered post-training, in influencing retention of an inhibitory avoidance response. Male CD1 mice (23-28 g) were trained in an inhibitory avoidance task, given immediate post-training ip injections of saline or GABAergic and adrenergic drugs administered either alone or concurrently. Retention was tested 48 h later. In agreement with extensive previous evidence, the GABAergic antagonist bicuculline (0.3, 1.0, or 3.0 mg/kg) produced dose dependent (inverted-U) enhancement of retention and the GABAergic agonist muscimol (1.0 mg/kg) impaired retention. The retention-enhancing effects of bicuculline were blocked by concurrent administration of the beta-nor adrenoceptor antagonist propranolol (2.0 mg/kg). Also in agreement with previous evidence, the beta-adrenoceptor agonist clenbuterol (0.030, 0.100, or 0.300 mg/kg, ip) produced dose-dependent (inverted-U) enhancement of retention. Clenbuterol also blocked the retention-impairing effects of muscimol (1.0 mg/kg). In addition, propranolol (2.0 mg/kg) potentiated the retention impairing effects of muscimol (1.0 or 3.0 mg/kg, ip). These findings support the view that GABAergic systems modulate memory through an interaction with beta-noradrenergic mechanisms. PMID- 8204081 TI - Comparable dose-response functions for the effects of glucose and fructose on memory. AB - A passive avoidance-to-active avoidance negative transfer paradigm was used to investigate in rats the effects of glucose and fructose on recently acquired memories. Immediate post-passive avoidance conditioning injections of glucose, fructose, or saline were followed 48 h later by active avoidance conditioning. Equimolar 10, 32, 100, and 2000 mg/kg sc doses of the two sugars significantly impaired acquisition of the reversal task, whereas 3.2 mg/kg doses of both sugars were without significant effect on subsequent performance and 320 mg/kg doses of both sugars significantly enhanced subsequent performance. The cubic trends for both dose-response functions were statistically significant and did not differ from each other. This is the first demonstration that glucose and fructose affect recently acquired memories in accord with comparable cubic dose-response functions, and that there are doses of both sugars that can enhance memory (as indicated by an increase in the number of trials required to reach criterion on the reversal task) and doses of both sugars that can impair memory (as indicated by a decrease in the number of trials required to reach criterion on the reversal task), compared to saline treatment. The similar cubic dose-response functions for glucose and fructose suggest that their mechanisms of action when they are injected peripherally are similar. In addition, because fructose does not readily pass the blood-brain barrier, the results suggest that these two monosaccharides may act through a common peripheral pathway. PMID- 8204082 TI - The effects of pregnenolone on acquisition and retention of a food search task. AB - Two experiments were undertaken in which the effects of semichronic administration of the precursor steroid, pregnenolone, were examined in a food search task. In both experiments male rats were required to find a food reward in a designated hole in an arena with 16 equally spaced holes. Hormone administration began 8 days before the onset of training. Training was given on an every-other-day schedule for five sessions. Animals were deprived of food for 18 h before training or testing. Retention testing occurred 10 days after acquisition and this was followed by 2 days of training using a different hole for the reward. The two experiments differed only in the method of hormone administration. In one experiment the rats received an implanted (sc) slow release pellet containing pregnenolone before training. In the second experiment the animals received ip injections of pregnenolone sulfate before and during initial training and then had the slow release pellet implanted between acquisition and retention. Significant enhancement of retention was found during the middle trials of the retention test when the treated and control groups from the two experiments were combined. No differences were found during acquisition training in either experiment. On the first day of training the animals to find the reward in a new location, the group injected with pregnenolone sulfate and later implanted with pregnenolone slow-release pellets exhibited performance superior to that of their matched control group. PMID- 8204083 TI - Pavlovian inhibitory conditioning and tolerance-reversal to scopolamine-induced adipsia in rats. AB - In the present experiment the effect of a conditioned inhibitory stimulus on tolerance to scopolamine-induced adipsia was evaluated. Long-Evans rats were injected with 0.6 mg/kg scopolamine bromidrate in the presence of a tone or a noise, and physiological saline with a compound tone-odor. A summation test with the compound stimulus noise-odor showed a tolerance reversal effect to scopolamine adipsic effects in tolerant subjects. This reduction of tolerance was similar to adipsia produced by the first scopolamine administration, only when the odor stimulus was present. However, the inhibitory stimulus alone has no effect upon water intake. Results confirmed that a Pavlovian conditioned inhibition procedure can reduce conditioned tolerance to a drug. PMID- 8204084 TI - Baclofen produces dose-related working memory impairments after intraseptal injection. AB - Altering the activity of the septohippocampal pathway can impair spatial memory in rats. Pharmacological manipulation of septal GABA-A receptors with the agonist, muscimol, or the benzodiazepine agonist, chlordiazepoxide, also impairs spatial memory and depresses hippocampal cholinergic activity. The present experiment examined the effects of intraseptal infusion of the GABA-B agonist baclofen on the performance of rats on a working memory radial arm maze (RAM) task. Post-training administration of baclofen (3 nmol, but not 1.5 or 0.75 nmol) produced a significant impairment of RAM performance. Baclofen significantly reduced the number of correct choices and increased the number of errors committed during testing without affecting latency per arm choice or the ability of the rats to navigate the maze and consume food pellets. The data suggest that baclofen impaired retention of the task without producing proactive performance deficits. Furthermore, the present data are consistent with the hypothesis that a GABAergic mechanism in the medial septum modulates the maintenance or retrieval of spatial working memory. PMID- 8204085 TI - Chronic corticosterone treatment impairs spontaneous alternation behavior in rats. AB - The present study used behavioral and morphological measures to assess hippocampal integrity in adult male rats after 8 weeks of daily corticosterone (10 mg/kg) injections. Behavioral testing during the final week of treatment revealed that spontaneous alternation behavior, a behavioral marker of hippocampal damage, was reduced in experimental animals without influencing exploration. Physiological assessment indicated that steroid exposure produced functional changes characteristic of prolonged exposure to stress or elevated plasma corticosterone, i.e., lower body weight and thymic involution. However, hippocampal cell loss was not observed in experimental rats. The data suggest that prolonged elevation of plasma corticosterone may significantly disrupt a hippocampal-sensitive behavior without producing gross morphological changes. PMID- 8204086 TI - Honeybee olfactory sensilla behave as integrated processing units. AB - Honeybee placode sensilla contain 18-35 olfactory receptor neurons. In insects, such neurons are thought to not interact with one another before reaching the central nervous system. Extracellular, multiunit recordings were made from the placodes and separated into spike shape classes, termed subplacode units. An analysis of the response spectra of subplacode units demonstrated that subplacode units with similar response spectra were more likely to be found in different placodes than in the same placode. An analysis was made of the mean interspike intervals and its variation for whole placodes and subplacode units. The coefficient of variation for whole placodes was less than that for subplacode units. Whole placode spike trains are therefore more uniform than subplacode spike trains, indicating that neurons might not be firing independently of each other. PMID- 8204087 TI - Differential recovery of inhibitory avoidance learning by striatal, cortical, and mesencephalic fetal grafts. AB - Four groups of male Wistar rats showing disrupted inhibitory avoidance conditioning due to striatal lesions were studied. Three groups received striatal, cortical, or ventral mesencephalic brain grafts and the fourth group remained as a lesioned control. Sixty days postgraft the animals were retrained in an inhibitory avoidance task. The striatal-grafted animals were the only group that significantly improved in the ability to acquire the inhibitory avoidance task. Acetylcholinesterase histochemistry revealed positive patches of cells in the striatal grafts. Cortical grafts showed less reactivity, without patches. Immunocytochemical analyses for tyrosine hydroxylase revealed positive cell reactivity in the mesencephalic grafts and few positive fibers were detected in the border between the striatal grafts and the host tissue. These results demonstrate that striatal but not cortical or mesencephalic brain grafts can promote the restoration of the ability to acquire an inhibitory avoidance task and suggest that the acetylcholine tissue content is involved in the behavioral recovery. PMID- 8204088 TI - The blood-brain barrier and multiple sclerosis. PMID- 8204089 TI - Alpha-lipoic acid reduction by mammalian cells to the dithiol form, and release into the culture medium. AB - Lipoic acid has been reported recently to be an effective antioxidant in biological systems. It may act in vivo through reduction to its dithiol form, dihydrolipoic acid. Using a dual Hg/Au electrode, and HPLC with electrochemical detection, a method was developed which allowed simultaneous measurement of lipoic acid and dihydrolipoic acid, at nanomolar levels. (RS)-alpha-Lipoic acid was added to human cells in tissue culture (Jurkat T-lymphocytes and primary neonatal diploid fibroblasts). Lipoic acid was converted rapidly by the cells to dihydrolipoic acid, which accumulated in the cell pellet. Monitored over a 2-hr interval, dihydrolipoic acid was released, and several-fold more dihydrolipoic acid could be found in the medium than in the pellet. PMID- 8204090 TI - Nitroblue tetrazolium inhibits oxidation of glyceryl trinitrate to nitric oxide in bovine aortic smooth muscle cells. AB - The effects of nitroblue tetrazolium (NBT), a well-known scavenger of superoxide anions and an inhibitor of nicotinamide adenine dinucleotide (NADPH)-dependent oxidations, were assessed on the metabolism of glyceryl trinitrate (GTN) to nitric oxide (NO) by bovine aortic smooth muscle cells (SMC). The extent of this metabolism was determined by measuring NO formed, using the inhibition of thrombin-induced platelet aggregation and relaxation of rabbit aortic strips as bioassay systems. In addition, NO produced from GTN by SMC was measured as nitrite (NO2-), one of its breakdown products. The antiplatelet effect of GTN (44 microM) was potentiated by SMC (0.12-0.46 x 10(5) cells) treated with indomethacin (10 microM) and this was inhibited in a concentration-dependent manner when the cells were pretreated with NBT (100 microM). NBT (3-100 microM) also reduced the formation of NO2- from GTN (600 microM) by SMC (3 x 10(5) cells). Furthermore, relaxations of endothelium-denuded strips of the rabbit aorta by GTN (10(-9)-10(-6) M) were attenuated when the strips were pretreated with NBT (100 or 500 microM). The formation of NO from L-arginine (L-Arg) by SMC was not affected by NBT. The hypotensive responses to GTN (0.25-1 mg/kg, i.v.) in anaesthetized rats were inhibited by pretreatment with NBT (1.25 mg/kg, i.v.) but NBT did not alter the hypotensive responses induced by SIN-1. Thus, NBT inhibited the bioconversion of GTN to NO both in vitro and in vivo. NBT may be a useful pharmacological tool to investigate the enzymic pathway(s) involved in the conversion of GTN to NO by smooth muscle cells or other cells. PMID- 8204091 TI - 2,6-Dichloro-4-nitrophenol (DCNP), an alternate-substrate inhibitor of phenolsulfotransferase. AB - 2,6-Dichloro-4-nitrophenol (DCNP)-35sulfate was identified and quantified by an HPLC-radiometric assay following its biosynthesis in vitro from 35S-labeled 3' phosphoadenosine-5'-phosphosulfate (PAP35S) by phenolsulfotransferase (PST) of rat liver cytosol. Acid hydrolysis of DCNP-35sulfate produced almost stoichiometric release of inorganic 35sulfate and DCNP. In two-substrate experiments of sulfation of p-nitrophenol (p-NP) or dopamine (prototype substrates for P and M human PST forms), 10 microM DCNP inhibited the reactions by about 15 and 78%, respectively. This contrasts with its action on PST of human origin where the P-PST was more sensitive to DCNP inhibition. In all mixed bi substrate experiments, a reciprocal relationship between the two sulfated products was observed. Kinetic data showed that p-NP inhibited the sulfation of DCNP competitively. Likewise the sulfation of p-NP and dopamine was competitively inhibited by DCNP. However, non-competitive inhibition was observed in the sulfation of p-NP by DCNP, measured at varying concentrations of PAP35S. The above kinetic data suggest that DCNP is an alternate-substrate inhibitor of rat liver PST. PMID- 8204092 TI - Ultrastructural and cytochemical changes in the heart of iron-deficient rats. AB - Male Sprague-Dawley rats aged 3 weeks that were maintained on an iron-deficient diet for 4-5 weeks developed severe anemia with markedly reduced hemoglobin levels (3.94 +/- 0.14 Hb g% versus controls 12.9 +/- 0.11 Hb g%). Iron-deficiency resulted in marked cardiac hypertrophy (cardiomegaly). On sacrifice, the hearts were processed for light and transmission electron microscopy. The major ultrastructural changes were found in the hypertrophied left ventricle and left papillary muscles. Iron-deficiency caused marked edema in myocytes, sarcomeres were out of register, and degeneration and discontinuities in myofilaments were common. Iron-deficiency resulted in the enlargement of the interfibrillar mitochondria, changes in the matrix and the formation of electron-dense amorphous bodies. The ultrastructural changes in myocytes in response to experimental iron deficiency were similar to those described by others in cases of experimental ischemia or hypoxia. Mitochondrial changes were also found in the atria of iron deficient rats. Quantitative cytochemical measurement of succinate dehydrogenase activity was determined and was shown to be substantially reduced in the iron deficient heart. In severely iron-deficient rats restored to a normal iron sufficient diet for two weeks, hemoglobin levels recovered, however the myocytes of the hypertrophied left ventricles and papillary muscles continued to show severe degenerative changes. PMID- 8204093 TI - Caffeine metabolism by human hepatic cytochromes P450: contributions of 1A2, 2E1 and 3A isoforms. AB - Caffeine (CA) N1-, N3- and N7-demethylase, CA 8-hydroxylase and phenacetin O deethylase activities were measured in microsomes from 18 separate human livers which had been characterized previously for a range of cytochrome P450 (CYP) isoform-specific activities and immunoreactive CYP protein contents. Correlations between the high affinity components of the three separate CA N-demethylations were highly significant (r = 0.77-0.91, P < 0.001) and each of the three high affinity CA N-demethylations correlated significantly (r = 0.64-0.93, P < 0.05 0.001) with the high affinity phenacetin O-deethylase, 2-acetylaminofluorene N hydroxylation and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2 amino-3-methylimidazo[4,5-f]quinoline (IQ) mutagenicity (all predominantly CYP1A2 mediated reactions). Consistent with these observations, cDNA-expressed human CYP1A2 catalyzed the N1-, N3- and N7-demethylation of CA and apparent Km values were similar (0.24-0.28 mM) for all three reactions and comparable to those observed previously with human liver microsomes. The low affinity components of CA N1- and N7-demethylation correlated significantly (r = 0.55-0.85, P < 0.05 0.001) with immunoreactive CYP2E1 content and the CYP2E1-specific activities 4 nitrophenol and chlorzoxazone hydroxylation. Diethyldithiocarbamate, a selective inhibitor of CYP2E1, inhibited the low affinity CA N1- and N7-demethylation, with IC50 values of 23 microM and 11 microM, respectively. The apparent Km values for CA N1- and N7-demethylation by cDNA-expressed CYP2E1 (namely 28 and 43 mM, respectively) were of a similar order to those calculated for the low affinity microsomal activities. Significant correlations (r = 0.87-0.97, P < 0.001) were observed between CA 8-hydroxylation and immunoreactive CYP3A content and the CYP3A-mediated reactions benzo(a)pyrene hydroxylation, omeprazole sulfoxidation and aflatoxin B1 mutagenesis. Effects of alpha-naphthoflavone, erythromycin, troleandomycin and nifedipine on microsomal CA 8-hydroxylation were generally consistent with CYP3A involvement. Taken together with previous data, the results indicate a major involvement of CYP1A2 in the high affinity component of all three human hepatic CA N-demethylations. In contrast, CYP2E1 appears to be the main enzyme involved in the low affinity components of CA N1- and N7 demethylation while CA 8-hydroxylation is catalysed predominantly by a CYP3A isoform(s). PMID- 8204094 TI - Similar toxic effect of 1,3-bis(2-chloroethyl)-1-nitrosourea on lymphocytes from human subjects differing in the expression of glutathione transferase M1-1. AB - Sixteen healthy donors were investigated for the presence or absence of glutathione transferase (GST) M1-1 in lymphocytes by immunodetection with polyclonal antibodies against human GST M1-1. Nine out of 16 individuals (56%) were categorized as GST M1-1 positive. Phytohaemagglutinin stimulated lymphocytes from GST M1-1 positive and negative donors were treated with 1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) and compared regarding inhibition of [3H]thymidine incorporation as a measure of cytotoxicity. No significant differences in the effect of BCNU were observed between the two groups, indicating that GST M1-1 is not an important resistance factor for BCNU. PMID- 8204095 TI - Rhein enhances the effect of adriamycin on mitochondrial respiration by increasing antibiotic-membrane interaction. AB - The effect of the combination of Adriamycin (ADM) with rhein (RH), an anti inflammatory drug, on the electron flow through site III and IV of the respiratory chain of rat liver mitochondria was investigated. RH, even at high concentrations, does not inhibit either duroquinol (DHQ) oxidation or cytochrome oxidase activity both of which are decreased by ADM in a dose-dependent manner. The analysis of interaction, performed with the isobolar method, shows a strong synergistic effect that cannot be ascribed to increased permeability of the mitochondrial membranes brought about by RH. The mechanism by which RH potentiates the effect of ADM on DHQ oxidation and cytochrome oxidase activity is most likely to be changes induced in the physical status of the inner mitochondrial membrane such as to permit low ADM concentrations to bind and segregate enough cardiolipin to inhibit electron transport through complex III and IV. PMID- 8204096 TI - Staurosporine up-regulates the expression of phorbol dibutyrate binding sites in human platelets. AB - Tumor-promoting phorbol esters bind to and activate protein kinase C (PKC). Staurosporine, a potent PKC inhibitor, interferes with PKC catalytic activity without altering phorbol ester binding sites in cell-free systems. We found that, unlike cell-free systems, treatment of intact platelets with staurosporine enhances the expression of phorbol 12, 13-dibutyrate (PDBu) binding sites. Incubation of platelets at 37 degrees with staurosporine (25 nM to 1 microM and 2 nM tritiated PDBu ([3H]PDBu) increased the amount of [3H]PDBu specifically bound to intact platelets by approximately 10 to 200% of control values. This effect was rapid and plateaued after 10 min of cell treatment. Scatchard analysis of the data showed that staurosporine (500 nM) significantly increased the total binding capacity Bmax from 42.9 +/- 15.4 x 10(3) to 78 +/- 7.3 x 10(3) sites per platelet and reduced the apparent dissociation constant value Kd from 30.8 +/- 8.6 nM to 9.4 +/- 3.4 nM. Enhanced PDBu binding capacity and affinity were also observed with human mononuclear and polymorphonuclear leukocytes. Fractionation of staurosporine-treated platelets showed an increased binding capacity of the particulate fraction (102%) and decreased binding capacity of the soluble fraction (60%) compared to controls, with no change in the affinity of PDBu binding to these fractions. Chelation of internal calcium with BAPTA did not significantly attenuate the staurosporine-mediated rise in PBDu binding but prevented the platelet-activating factor-induced response, indicating that cytosolic calcium does not play an important role in these staurosporine effects. These results show that, in addition to interfering with PKC protein phosphorylating activity, staurosporine enhances PDBu binding affinity and capacity in intact platelets. This latter effect appears to be due to translocation of soluble PDBu binding sites, presumably PKC units. PMID- 8204097 TI - 11 beta-hydroxysteroid dehydrogenase mediates reductive metabolism of xenobiotic carbonyl compounds. AB - The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) is considered to confer mineralocorticoid specificity on the non-selective Type I adrenocorticoid receptor by converting active 11-hydroxyglucocorticoids to receptor-inactive 11 oxo metabolites, in mineralocorticoid target tissues like the kidney. However, 11 beta-HSD is also present in the liver, where it may regulate steroid exposure to the glucocorticoid Type II receptor. Because of the much higher activities compared to that in kidney, liver 11 beta-HSD possibly has additional functions besides the metabolism of glucocorticoids. In the present investigation we have isolated 11 beta-HSD from mouse liver microsomes and demonstrate that the homogeneously purified enzyme is also capable of catalyzing the reductive metabolism of xenobiotic carbonyl compounds such as metyrapone, p nitroacetophenone and p-nitrobenzaldehyde. Enzyme kinetic studies revealed that, in addition to NADP+, mouse liver 11 beta-HSD also accepts NAD+ as cosubstrate for glucocorticoid 11 beta-dehydrogenation. NADH as cosubstrate for 11 oxoreduction plays only a minor role compared to that with NADPH, a fact which is also true for xenobiotic carbonyl reduction. Inhibition experiments revealed strong sensitivity of xenobiotic carbonyl reduction to glucocorticoids. The competitive nature of this inhibition suggests that both glucocorticoids and xenobiotic carbonyl substances bind to the same catalytically active site of 11 beta-HSD. High enzyme activities were also found in microsomal fractions of the ovary and adrenal gland but, although expressing considerable glucocorticoid 11 dehydrogenation activity (one third that of liver), almost no carbonyl reduction was detectable in kidney microsomes. Immunoblot analysis with polyclonal antibodies directed against the liver 11 beta-HSD did not yield an immunological crossreaction in the same tissues. In conclusion, corresponding to the cytosolic aldo-keto reductases, microsomal 11 beta-HSD of liver may be considered to play a role in the phase I biotransformation of pharmacologically relevant carbonyl substances as well as protecting organisms against toxic carbonyl compounds by converting them to less lipophilic and more soluble and conjugatable metabolites. Discrepancies in bioactivity together with the lack of response to anti-liver 11 beta-HSD antibodies strongly indicate the existence of distinct forms of 11 beta HSD to be present in kidney, adrenal gland and ovary. The ability of xenobiotic carbonyl reduction might be another distinguishing feature among the various 11 beta-HSD isozymes. PMID- 8204099 TI - Mitochondrial respiratory activity and superoxide radical generation in the liver, brain and heart after chronic ethanol intake. AB - Functional characteristics of mitochondria isolated from liver, brain and heart were studied in ethanol-fed rats using ethanol administration in drinking water as a model of moderate alcohol intoxication. Our results show a slight decrease in liver cytochrome aa3 content, the mitochondrial alteration which is most consistently observed during chronic ethanol feeding. In liver and heart mitochondria, ethanol consumption led to an increase in state 3 respiration with NAD(+)-linked substrates, whereas no changes were apparent in respiration rates with succinate as substrate. However a decrease was found in state 3 respiration with succinate in brain mitochondria isolated from ethanol-fed rats. Submitochondrial particles (SMP) were used to study the superoxide radical (O2-.) production at the level of antimycin-inhibited regions of the respiratory chain. It appears that there is no clear correlation between ethanol effects on respiration and O2-. production. Whereas O2-. generation remained unchanged in heart mitochondria, an elevation of O2-. generation was observed in brain mitochondria, and in contrast, the rate of O2-. production was decreased in liver mitochondria of the ethanol-group in comparison to the control-group. Our findings support a tissue specificity for the toxic effects of ethanol towards the mitochondria and indicate that mitochondrial free radical mechanisms are involved in ethanol-induced toxicity in the brain. PMID- 8204098 TI - Inhibition of the in vitro integration of Moloney murine leukemia virus DNA by the DNA minor groove binder netropsin. AB - In search of potential inhibitors of integration of retroviral DNA into host cells genome, we have investigated the effect of the external DNA binder netropsin on the in vitro insertion of long terminal repeat (LTR) ends of Moloney murine leukemia virus (M.MuLV) as catalysed by integrase purified from baculovirus strain expression vector. In agreement with the preferential binding of netropsin to A+T rich sequences, footprinting experiments have shown that this drug selectively binds to the 5'-TTTCAT LTR end sequence which is included in the DNA binding site of integrase. This feature results in the potent inhibition of both reactions involved in the insertion process, namely, nucleolytic cleavage and strand transfer. The relation between netropsin binding to A+T rich region of M.MuLV LTR end and inhibition of insertion is strongly suggested from the inability of the drug to inhibit the insertion of HIV U3 LTR end which displays a G+C rich sequence. Selective inhibition of integration of viral DNA appears to be feasible using drugs recognizing LTR end sequences. PMID- 8204100 TI - Effects of acute ethanol administration on the uptake of 59Fe-labeled transferrin by rat liver and cerebellum. AB - The uptake of iron by the liver and cerebellum was measured in rats using [59Fe]transferrin. An acute ethanol load (50 mmol/kg body wt., i.p.) elicited a significant increase in the hepatic and cerebellar non-heme iron concentration. The uptake of 59Fe by the liver and the cerebellum was significantly greater in the ethanol-treated rats than in control animals. The administration of allopurinol prior to the ethanol load prevented the changes in liver and cerebellar non-heme iron content. Moreover pretreatment with allopurinol reduced the ethanol-induced enhancement of 59Fe uptake by the liver and completely prevented the changes in 59Fe uptake by the cerebellum. These effects of allopurinol lead us to suggest that oxygen-derived free radicals are involved in the ethanol-induced disturbances of iron uptake both at the hepatic and cerebellar level. PMID- 8204101 TI - Iron uptake from ferrioxamine and from ferrirhizoferrin by germinating spores of Rhizopus microsporus. AB - Mucormycosis caused by the fungus Rhizopus has been documented in iron overloaded patients and more particularly in dialysis patients, both when treated with desferrioxamine B (DFO). This iron and aluminium chelator is thought to play a role in the pathogenesis of this infection. We therefore investigated in vitro the cellular pharmacology of iron chelated by DFO in the fungus Rhizopus. In a medium, designed for fungal cultivation, Rhizopus microsporus var. rhizopodiformis takes up iron from ferric-DFO complex (55Fe.DFO) and from 55Fe.rhizoferrin, the siderophore synthesized and secreted by Rhizopus [Drechsel et al., Biol. Metals 4: 238-243, 1991]. In both cases, iron accumulation is partially saturable with the duration of exposure and the chelator concentration. Fe.DFO binds to Rhizopus; iron becomes trapped and remains associated with the fungus, whereas the iron-depleted siderophore is released in the extracellular medium. In a medium designed for mammalian cell cultivation and in the absence of human serum, the fungal iron accumulation both from 55Fe.DFO and from 55Fe.rhizoferrin is proportional to the chelator concentration. Human serum at 40% does not influence the iron accumulation from Fe.DFO but it significantly affects that from Fe.rhizoferrin which, in the presence of serum, only occurs at concentration > 5 microM. This difference finds its explanation in the iron transfer observed between Fe.rhizoferrin and seric apotransferrin, the latter making the metal unavailable to Rhizopus. By contrast, no iron transfer takes place between Fe.DFO and apotransferrin, allowing fungal iron utilization from this complex, even at very low concentrations. The iron uptake, being inhibited by NaN3 and KCN, is energy-dependent; being inhibited by bipyridyl, it requires prior reduction of ferric iron; being unaffected by the covalent linkage of Fe.DFO to albumin, it does not require the entry of Fe.DFO within the fungus. These in vitro results strongly suggest that, upon administration of DFO to iron overloaded or dialysis patients, the formed Fe.DFO is efficiently used as an iron source by Rhizopus, even in the presence of serum apotransferrin or rhizoferrin. The consequent promotion of the growth of Rhizopus helps explain the increased risk of mucormycosis in DFO-treated patients. PMID- 8204103 TI - Putrescine uptake inhibition by aromatic diamidines in Leishmania infantum promastigotes. AB - The effect of a series of aromatic diamidines has been tested on Leishmania infantum promastigotes in both culture growth and putrescine uptake. The EC50 values calculated by means of dose-response curves were 45, 80, 165, 259 and 600 microM for 4', 6-diamidino-2-phenylindole (DAPI), dibromo propamidine, pentamidine 2-hydroxy stilbamidine and stilbamidine, respectively, although no inhibitory effects on cell growth were found at 1 mM propamidine, phenamidine and amicarbalide. When these compounds were kinetically analysed for putrescine uptake using Lineweaver-Burk plots, the Ki values reached were: DAPI, 15 microM; pentamidine, 3 microM; dibromo propamidine, 7 microM; 2-hydroxy stilbamidine, 21 microM; stilbamidine, 20 microM; propamidine, 25 microM; and phenamidine, 95 microM. Amicarbalide, however, was not able to reduce putrescine uptake to a significant extent, even at the highest concentration studied of 1 mM. PMID- 8204102 TI - Correlation between the short-term measurements of drug accumulation in living cells and the long-term growth inhibition. AB - The basic distinguishing feature of all cells expressing functional P glycoprotein-multidrug resistance (P-gp-MDR) is a decrease of steady state drug levels as compared to drug-sensitive controls. Recently it has been pointed out that there appears to be a discrepancy between the amount of drug accumulated at steady state by drug-sensitive and highly resistant cells and their degree of resistance. These observations could suggest two things: (1) that factors other than drug accumulation may be important in MDR, (2) that they reflect a discrepancy between the short-term measurements of drug accumulation at 60 min versus long-term (72 hr) growth inhibition. Due to the different experimental conditions and the different type of cells used it is very difficult to compare the literature data. For this reason we have investigated the effect of 12 compounds in overcoming resistance in relation to drug accumulation. We have used a spectrofluorometric method which allows the determination of the nuclear drug accumulation directly on living cells. Our data clearly establish that, at least for the compounds used in that study, there is a very good correlation between their ability to increase drug accumulation, measured at short-term, and their ability to reverse MDR accumulation, measured at short-term, and their ability to reverse MDR, but no correlation with their ability to inhibit protein kinase C activity. In addition, their efficiency to reverse MDR correlates with their pKa values, the efficiency being the highest when the pKa is the lowest. PMID- 8204104 TI - Inducibility of various cytochrome P450 isozymes by phenobarbital and some other xenobiotics in Drosophila melanogaster. AB - The inducibility of cytochrome P450 isozymes has been investigated in the Drosophila melanogaster insecticide susceptible (Oregon R) and insecticide resistant (91R) strains. Both the level and induction kinetics of 7 ethoxycoumarin O-deethylase activity were stimulated by phenobarbital (PB) to a lower extent than that of aryl hydrocarbon hydroxylase in the Oregon R strain. The basal level of the cytochrome P450-linked activities in insecticide resistant flies was higher than that noted in susceptible ones. However, treatment with PB has increased levels of 7-ethoxycoumarin O-deethylase and aryl hydrocarbon hydroxylase activities more in susceptible flies than in resistant ones. In contrast to PB, the polycyclic aromatic hydrocarbon benzo[a]pyrene induced both activities in 91R flies to a greater extent than in Oregon R ones. The potent PB like inducer in mice but not in rats 1.4-bis[2-(dichloropyridyloxy)]-benzene failed to induce the cytochrome P450 system in D. melanogaster, when triphenyldioxane (PB-like inducer in rats but not in mice) markedly affected this system in a PB-like manner. The SDS-PAGE followed by immunoblotting analysis using monoclonal antibodies 13-2e and 8-1d have shown that the level of the 56,000 and 54,000 Da insecticide resistance-related forms has increased in the susceptible strain by PB and some other PB like inducers. The relationship between these isozymes appearance and 7-ethoxycoumarin O-deethylase activity has been discussed. PMID- 8204105 TI - Cytochalasin B may shorten actin filaments by a mechanism independent of barbed end capping. AB - It is generally accepted that cytochalasin B (CB), as well as other cytochalasins, shorten actin filaments by blocking monomer addition at the fast growing ("barbed") end of these polymers. Despite the predominance of this mechanism, recent evidence suggests that other interactions may also occur between CB and F-actin. To investigate this possibility further we have employed an actin derivative, prepared by substitution at Cys374 by a glutathionyl residue. We demonstrate here that CB did not significantly bind to glutathionyl F actin under several ionic conditions. We further show that in the presence of CB the glutathionyl-F-actin exhibits a significantly higher ATPase activity than the non-modified F-actin. These data argue that the incorporation of glutathionyl groups prevents the high-affinity binding of CB to the barbed end of actin filaments, probably due to a decreased hydrophobicity of the CB binding site by the introduction of the hydrophilic glutathionyl residue. Despite the lack of substantial binding at equilibrium, we have found that the addition of CB to glutathionyl-F-actin results in extensive fragmentation of the filaments, as demonstrated by electron microscopy and by a significant reduction of the relative viscosity of actin solutions. These results are consistent with the idea that CB shortens glutathionyl-actin filaments by a mechanism distinct from barbed end capping. Glutathionyl F-actin offers an interesting model to study the complex mechanism of interaction of actin filaments with cytochalasins and with the physiologically important actin capping/severing proteins. PMID- 8204106 TI - Involvement of cytochrome P450 3A enzyme family in the major metabolic pathways of toremifene in human liver microsomes. AB - The anti-estrogen toremifen-Fc-1157a or 4-chloro-1,2-diphenyl-1-[4-[2(N,N dimethylamino)ethoxy]-phenyl]-1- butene is now used for the treatment of breast cancer. This drug is extensively metabolized by cytochrome P450 dependent hepatic mixed function oxidase in man, yielding mainly the N-demethyl-(DMTOR), 4-hydroxy (4OH-TOR) and deamino-hydroxy-(TOR III) toremifene metabolites. The specific forms of cytochrome P450 involved in these oxidation reactions were examined in 32 human liver microsomal preparations previously characterized with respect to their contents of several known P450 enzymes. Toremifene was demethylated with an apparent Km of 124 microM while it was hydroxylated with an apparent Km of 139 microM. The metabolic rates were 71 +/- 56, 13 +/- 9 and 15 +/- 4 pmol/min/mg microsomal protein, respectively, for DMTOR, 4-OH-TOR and TOR III. The N demethylation activity was strongly correlated with estradiol 2-hydroxylation (r = 0.75), nifedipine oxidation (r = 0.86), tamoxifen N-demethylation (r = 0.73), testosterone 6 beta-hydroxylation (r = 0.78) and erythromycin N-demethylation (r = 0.84), all these monooxygenase activities known to be supported by CYP3A4 isoform. Furthermore, the CYP3A content of liver microsomal samples, measured by western blot analysis using a monoclonal anti-human CYP3A4 antibody, was strongly correlated with DMTOR formation (r = 0.80). Compounds such as cyclosporin, triacetyl-oleandomycin and testosterone inhibited the N-demethylation of toremifene metabolism at 80, 89 and 56% vs control, respectively, while the formation of TOR III was inhibited at 78, 82 and 73% vs control and the 4 hydroxylation pathway was inhibited no more than about 50% vs control. Prior incubation of microsomes with 100 microM gestodene, known to be a selective mechanism-based inhibitor of CYP3A4 in the presence of NADPH, led to 76 +/- 6 and 76 +/- 5% (N = 5 samples) reductions in the N-demethylation and formation of TOR III, respectively. Polyclonal antibody directed against human CYP3A enzymes inhibited formation of DMTOR and TOR III by 60 and 46%, respectively. The metabolism of toremifene was not activated by alpha-naphthoflavone. Finally, the use of yeasts genetically engineered for expression of human P4501A1, 1A2, 2C9 and 3A4 allowed us to demonstrate that DMTOR and TOR III formations are mediated by P4501A and 3A4 enzymes and by contrast these enzymes are not involved in the 4 hydroxylation pathway.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8204107 TI - Effects of aminosalicylates and immunosuppressive agents on nitric oxide dependent N-nitrosation reactions. AB - Recent studies have demonstrated that nitric oxide (NO) rapidly and spontaneously decomposes in oxygenated solutions to generate potent N-nitrosating agents. These electrophilic substances have been shown to mediate mutagenesis and carcinogenesis via the formation of aliphatic and aromatic nitrosamines. We have also demonstrated that extravasated neutrophils and macrophages produce significant amounts of N-nitrosating agents derived exclusively from NO. During the course of these studies, we found that certain antioxidants, including 5 aminosalicylic acid (5-ASA), inhibited the leukocyte-mediated N-nitrosation reaction. Because 5-ASA and other anti-inflammatory and immunosuppressive drugs are used to treat inflammatory bowel disease, we wondered if any of these other compounds might also modulate N-nitrosation reactions in vitro. Therefore, the objectives of this study were to assess the ability of aminosalicylates and certain immunosuppressive agents to inhibit NO-dependent N-nitrosation of a model aromatic amine (2,3-diaminonaphthalene) and to determine whether this inhibitory activity correlated with their oxidation potential. We found that the concentrations necessary to inhibit the N-nitrosation reaction by 50% (IC50) were 25, 50 and 100 microM for 5-ASA, olsalazine (dimeric 5-ASA) and sulfasalazine, respectively. In contrast, sulfapyridine, 4-ASA, N-acetyl-5-ASA, 6 mercaptopurine, azathioprine, and methotrexate were either much less effective or inactive at inhibiting the N-nitrosation reaction. Although 5-ASA was able to fully scavenge the stable free radical 1,1-diphenyl-2-picrylhydrazyl, neither olsalazine nor sulfasalazine was found to be effective at scavenging this weak oxidant. We did find that olsalazine possessed an oxidation potential substantially less than that of sulfasalazine, suggesting that it may, in fact, scavenge more potent oxidizing agents such as the N-nitrosating agent. We conclude that 5-ASA and olsalazine inhibit NO-dependent N-nitrosation reactions by scavenging or decomposing the nitrosating agent(s). We propose that the secondary nitrogen unique to sulfasalazine interacts with the nitrosating agent to yield a secondary nitrosamine, thereby competing for N-nitrosation of our detector. PMID- 8204108 TI - Differential induction of glutathione S-transferase in rat aorta versus liver. AB - Polycyclic aromatic hydrocarbons, cigarette smoke components that induce atherosclerosis in animals, require metabolic biotransformation to electrophilic intermediates to exhibit atherogenic effects. The formation of reactive metabolites depends on both rates of cytochrome P450-catalyzed oxidation and rates of detoxification through conjugation with glutathione. Thus, changes in the activity of glutathione S-transferase in vascular tissue could affect the risk of polycyclic aromatic hydrocarbon-induced atherogenesis. We compared the effects of several exogenous chemicals on levels of glutathione S-transferase in aorta and liver. Male Wistar rats were treated with 3-methylcholanthrene, a polycyclic aromatic hydrocarbon, phenobarbital and butylated hydroxytoluene, an antioxidant known to have anti-atherogenic properties. In control animals, glutathione S-transferase activity was about 20-fold greater in liver than in aorta. Subunit expression was tissue specific. GST-Yp, for example, was the most abundant subunit in aorta but was undetectable in liver. In contrast, GST-Ya was barely detectable in aorta but was abundant in liver. Each of the xenobiotics caused induction of glutathione S-transferase but the extent of induction was greater in liver than in aorta. Phenobarbital, for example, caused 300% induction in liver but only 70% induction in aorta. By western blot analysis, differences in amounts of enzyme subunits corresponded to changes in enzyme activity. Thus, exogenous chemicals differentially regulate levels of glutathione S-transferase in the aorta and liver. PMID- 8204109 TI - Effects of long-chain fatty amines on the growth of ras-transformed NIH 3T3 cells. AB - A number of aliphatic primary amines were tested for their effects on the growth of ras-transformed NIH 3T3 cells (PAP2 cells), as measured by incorporation of tritiated thymidine into DNA. Long-chain, saturated amines (C12 to C18) were growth inhibitory, whereas short-chain amines (C6, C8) were not. Farnesylamine, a branched-chain, unsaturated amine (C15), had an IC50 of 6.9 microM compared to IC50 values of 13.1 to 45.8 microM for straight-chain, saturated amines. Oleylamine, with an IC50 of 0.1 microM, was the most potent inhibitor. The long chain amines, but not the short-chain amines, were also effective inhibitors of protein kinase C, assayed in vitro in a cell-free system. In addition, studies with indo-1-loaded PAP2 cells showed that long-chain amines induced a reversible rise in intracellular free Ca2+ concentration. Growth inhibition by the amines was positively correlated with this effect, suggesting that factors other than protein kinase C may be involved in the inhibition of growth of PAP2 cells by long-chain amines. PMID- 8204110 TI - Site-specific DNA cleavage by Cu(II) complexes of podophyllotoxin derivatives. AB - Site-specific DNA cleavage in the presence of Cu(II) complexes of podophyllotoxin derivatives was investigated with a modified Sanger sequencing method. Cu(II) complexes of 4'-demethylepipodophyllotoxin (DEPD) and syringic acid (SA) cleaved M13mp18 single-strand DNA site-specifically at both cytosine (C) and guanine (G) positions in the GC rich regions and C position, respectively, at pH 7.8. The apparent binding constants of calf thymus DNA-Cu(II) complexes estimated by the differential UV-absorption spectra revealed that both Cu(II)-VP-16 and -DEPD complexes bind to DNA more strongly than does the Cu(II)-SA complex. PMID- 8204111 TI - Benign parotid cysts associated with human immunodeficiency virus infection. PMID- 8204112 TI - Recruiting for primary care. PMID- 8204113 TI - Paresis in young ostriches. PMID- 8204114 TI - Drugs from Third World plants: creative approaches. PMID- 8204115 TI - Histopathology of human immunodeficiency virus-associated esophageal disease. AB - We evaluated the histopathologic features of the esophageal mucosa in 88 patients seropositive for human immunodeficiency virus (HIV). All patients had an upper endoscopy because of esophageal symptoms. Forceps biopsies and brushings of the esophagus were examined histologically and cytologically for evidence of viral, fungal, and mycobacterial infections: in addition, biopsies and brushings were cultured for cytomegalovirus and herpes simplex. Esophageal inflammation (acute or chronic) was graded 0 through 3. Twenty-one patients (24%) had a normal endoscopy; none displayed high grade (grade 2 and 3) acute inflammation and only two (9.5%) had high grade chronic inflammation in the esophagus. Moreover, no fungi or viral inclusions were seen in samples from these patients. Eleven patients (12%) had an abnormal esophageal mucosa but no pathogen detected and were categorized as "idiopathic esophagitis." The percent with high-grade inflammation (27%) was not significantly different from the normal group. Fifty six patients (64%) had an infectious diagnosis. Forty-six percent had Candida, 16% had viral esophagitis alone, and one patient had Kaposi's sarcoma. Infections were associated with high-grade acute and chronic inflammation in 53% and 47% of patients, respectively. The location of the infiltrate did not predict the type of infection. In conclusion, if esophagoscopy is normal in patients with HIV infection and esophageal symptoms, a biopsy is not necessary. PMID- 8204116 TI - AIDS. The unanswered questions. PMID- 8204117 TI - Cannabis in the external ear. AB - ENT surgeons may well be asked to remove cannabis from the external ear where it has been lodged for various reasons. We report two cases and review four other cases we found in the literature to illustrate some of the difficulties. It is important that anyone working with people who abuse drugs are aware that cannabis can be concealed in the external ear. PMID- 8204118 TI - [Clinical experiences with passive immunotherapy in habitual abortion]. AB - In a pilot study, 25 patients with histories of repeated abortion were treated by passive immunotherapy with high-dosage immunoglobulin administration (Sandoglobulin). Plasma viscosity, RBC aggregation, hematocrit, PAI, D-dimer and Factor VIIIR:AG were studied in order to detect risks. By September 1, 1992, 16 women had given birth; abortion had recurred in 2 women and 7 were pregnant between the 10th and 37th GW. Five pregnancies terminated in premature/small-for date births and one neonate had a congenital malformation syndrome. Under immunoglobulin therapy no hyperviscosity or excessive fibronolysis defects with a tendency to thrombosis or restriction of intervillous perfusion were observed. Besides safety for mother and fetus, intravenous immunoglobulin administration has the added advantage that it can be used in cases of primary and secondary abortion and for women with deficient immune response. PMID- 8204119 TI - More on sucrose and the effect of lyophilization on determination of lipoprotein(a) in serum. PMID- 8204120 TI - French appeal court sends Allain to jail. PMID- 8204121 TI - Financial conflicts of interest in biomedical research. PMID- 8204122 TI - The missing AIDS science. PMID- 8204123 TI - An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. AB - BACKGROUND: The relative efficacy of streptokinase and tissue plasminogen activator and the roles of intravenous as compared with subcutaneous heparin as adjunctive therapy in acute myocardial infarction are unresolved questions. The current trial was designed to compare new, aggressive thrombolytic strategies with standard thrombolytic regimens in the treatment of acute myocardial infarction. Our hypothesis was that newer thrombolytic strategies that produce earlier and sustained reperfusion would improve survival. METHODS: In 15 countries and 1081 hospitals, 41,021 patients with evolving myocardial infarction were randomly assigned to four different thrombolytic strategies, consisting of the use of streptokinase and subcutaneous heparin, streptokinase and intravenous heparin, accelerated tissue plasminogen activator (t-PA) and intravenous heparin, or a combination of streptokinase plus t-PA with intravenous heparin. ("Accelerated" refers to the administration of t-PA over a period of 1 1/2 hours- with two thirds of the dose given in the first 30 minutes--rather than the conventional period of 3 hours.) The primary end point was 30-day mortality. RESULTS: The mortality rates in the four treatment groups were as follows: streptokinase and subcutaneous heparin, 7.2 percent; streptokinase and intravenous heparin, 7.4 percent; accelerated t-PA and intravenous heparin, 6.3 percent, and the combination of both thrombolytic agents with intravenous heparin, 7.0 percent. This represented a 14 percent reduction (95 percent confidence interval, 5.9 to 21.3 percent) in mortality for accelerated t-PA as compared with the two streptokinase-only strategies (P = 0.001). The rates of hemorrhagic stroke were 0.49 percent, 0.54 percent, 0.72 percent, and 0.94 percent in the four groups, respectively, which represented a significant excess of hemorrhagic strokes for accelerated t-PA (P = 0.03) and for the combination strategy (P < 0.001), as compared with streptokinase only. A combined end point of death or disabling stroke was significantly lower in the accelerated-tPA group than in the streptokinase-only groups (6.9 percent vs. 7.8 percent, P = 0.006). CONCLUSIONS: The findings of this large-scale trial indicate that accelerated t PA given with intravenous heparin provides a survival benefit over previous standard thrombolytic regimens. PMID- 8204124 TI - Problems in primary care. PMID- 8204125 TI - Postremission therapy for the younger adult patient with acute myelogenous leukemia: defining a role for transplantation. PMID- 8204126 TI - Poison center data misleading. PMID- 8204127 TI - Simplifying the diagnosis of obstructive sleep apnea. PMID- 8204128 TI - Attention deficit-hyperactivity disorder. PMID- 8204129 TI - Guidelines for the treatment of gallstones. American College of Physicians. PMID- 8204130 TI - Citizens' advice in general practice. A burden GPs could do without. PMID- 8204131 TI - Distinct criteria for termination of resuscitation in the out-of-hospital setting. AB - OBJECTIVE: To identify distinct criteria for appropriate on-scene termination of resuscitation efforts for out-of-hospital cardiac arrest when on-scene interventions fail to restore spontaneous circulation. DESIGN: For 18 months, all out-of-hospital cardiac arrests were evaluated prospectively for survival to hospital discharge and for all established survival predictors including age, gender, presenting cardiac rhythm, whether it was a witnessed event, performance of basic cardiopulmonary resuscitation by bystanders, and interval to paramedic arrival and return of spontaneous circulation (ROSC). SETTING: A large municipality with a single, centralized emergency medical services program. PATIENTS: All normothermic adults treated for out-of-hospital, unmonitored, primary cardiac arrest. INTERVENTIONS: Standard advanced cardiac life support provided at the scene by paramedics. MAIN OUTCOME MEASURES: The number and circumstances of patients achieving survival to hospital discharge following failure to achieve on-scene ROSC. RESULTS: Of 1461 consecutive primary cardiac arrests, 139 were monitored (paramedic witnessed), including 59 that occurred en route to the hospital. Of the 1322 unmonitored patients, 370 achieved ROSC at the scene. Only six (0.6%) of the 952 who did not achieve ROSC at the scene survived, and all six were readily identifiable as having persistent ventricular fibrillation. Excluding those patients with persistent ventricular fibrillation, all survivors achieved ROSC within 25 minutes after paramedic arrival. CONCLUSIONS: Excluding patients with persistent ventricular fibrillation, resuscitative efforts can be terminated at the scene when normothermic adults with unmonitored, out-of-hospital, primary cardiac arrest do not regain spontaneous circulation within 25 minutes following standard advanced cardiac life support. These criteria should now be validated in several large centers with high survival rates. PMID- 8204132 TI - Diagnosis of osteomyelitis: utility of fat-suppressed contrast-enhanced MR imaging. AB - PURPOSE: To assess the value of fat-suppressed contrast material-enhanced magnetic resonance (MR) imaging in the diagnosis of osteomyelitis. MATERIALS AND METHODS: T1- and T2-weighted MR imaging was performed in 51 cases of suspected osteomyelitis. Nonenhanced and contrast-enhanced T1-weighted fat-suppressed MR images were also obtained. Three-phase bone scan results were available for 30 cases. Complicating clinical factors, including chronic osteomyelitis (n = 26), postoperative state (n = 17), and neuropathic disease of the foot (n = 5), were identified in 73% of cases. RESULTS: In the diagnosis of osteomyelitis, scintigraphy demonstrated a sensitivity of 61% and specificity of 33%. For nonenhanced MR imaging, sensitivity was 79% and specificity was 53%. For fat suppressed contrast-enhanced imaging, sensitivity was 88% and specificity was 93%. CONCLUSION: In diagnosing osteomyelitis in patients with complicating clinical factors, fat-suppressed contrast-enhanced MR imaging was significantly more sensitive than scintigraphy (P = .04) and significantly more specific than nonenhanced MR imaging (P = .02) or scintigraphy (P = .008). PMID- 8204133 TI - Internal standards in gas-chromatographic analyses for ethylene glycol in serum. PMID- 8204134 TI - Assessment of dioxin-related health risks for the Melbourne metropolitan area. AB - A community health risk assessment was conducted during 1990 in Melbourne for polychlorinated dibenzo-para-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) released in Laverton North by Nufarm Limited, an agricultural chemicals manufacturer. This risk assessment incorporated current scientific knowledge into hazard identification, dose-response assessment, exposure assessment and risk characterisation sections, according to the four-step framework used by the United States Environmental Protection Agency. The hazard identification showed that health effects are unlikely to result from general population exposures to PCDDs and PCDFs. The dose-response assessment supported a safety-factor approach for PCDD and PCDF risk assessment. The exposure assessment incorporated exaggerated assumptions to estimate both total daily exposure (203 pg total toxic equivalents of PCDDs and PCDFs, or 2.9 pg/kg body weight) and daily exposure attributable to Nufarm (56.4 pg, or 0.80 pg/kg body weight) under a worst-case scenario. The risk characterisation section found that exposures under 20 pg/kg body weight per day should not induce the aryl hydrocarbon hydroxylase system, which appears to be the starting point for PCDD and PCDF toxicity. We concluded that the general population exposure to PCDDs and PCDFs in Melbourne was within the range of acceptable daily intakes used by European and Canadian governments and the World Health Organization, as well as within the range of acceptable daily intakes derived using current scientific knowledge. PMID- 8204135 TI - Transmission of HIV in prison. Evidence of risk. PMID- 8204136 TI - Patient financial arrangements: make them profitable. PMID- 8204137 TI - Geriatric medicine: a true subspecialty. PMID- 8204138 TI - Medical treatment preferences of nursing home residents: relationship to function and concordance with surrogate decision-makers. AB - OBJECTIVE: To describe treatment preferences of nursing home residents, concordance with decisions by self-selected proxies and to establish the relationship of sociodemographic and functional measures to decisions. SETTING AND SUBJECTS: 52 patient-proxy pairs at a Veterans Affairs nursing home. METHODS: Treatment preferences were elicited from residents and proxies regarding cardiopulmonary resuscitation, mechanical ventilation, and intensive care unit care. Hospitalization, intravenous antibiotics, intravenous fluid administration, and tube feeding were presented in three separate health scenarios. Concordance was determined for the entire interview and separately for each scenario. Treatment-seeking intensity and decision-making consistency were scored and used to explore associations with sociodemographic variables and function. RESULTS: Subjects were predominantly male (97%) and non-Hispanic white (74%); average age was 70 +/- 12 years, with 4 +/- 2.9 diagnoses. Residents accepted 70% of all treatments. The proportion of subjects accepting interventions declined parallel to health status in each scenario. Only 7/52 (13%) subjects made inconsistent decisions. Resident treatment acceptance was inversely associated with GDS scores but not associated with any other sociodemographic or functional measure. Concordance with proxies was no greater than chance. Proxies' decisions were not systematically biased against resident preferences or influenced by patient characteristics. CONCLUSIONS: Veterans desired most treatments, but adjusted preferences according to health status and were not inconsistent. Depressive symptoms should be addressed prior to advance directive selection. The patient remains the best source of information, but proxies' decisions exhibit no bias and are not affected by patient status. PMID- 8204139 TI - Medical practice under the Clinton reforms--avoiding domination by business. PMID- 8204140 TI - Borna disease in ostriches. PMID- 8204141 TI - Babies' rectal temperature. Is a rectal temperature always necessary. PMID- 8204142 TI - Therapeutic potential of aspirin in cancer of the colon. PMID- 8204143 TI - Occupational overuse syndrome. PMID- 8204144 TI - Bupivacaine toxicity secondary to continuous caudal epidural infusion in children. PMID- 8204145 TI - Rheumatoid arthritis, impairment and mobility. PMID- 8204146 TI - Undergraduate critical care education. PMID- 8204147 TI - Continuous subdural block. PMID- 8204148 TI - The management of acute poisoning. PMID- 8204149 TI - A discussion of "The detection and documentation of trace wound pattern by use of an alternative light source". PMID- 8204150 TI - Diagnosis of placental infarction. PMID- 8204151 TI - What role for nurse practitioners in primary care? PMID- 8204152 TI - "Vaginal delivery of the nonvertex second twin": does this study have a type II error? PMID- 8204153 TI - Prophylactic amnioinfusion and meconium aspiration syndrome. PMID- 8204154 TI - Why not the elimination of tuberculosis? PMID- 8204155 TI - More therapeutic conservatism. PMID- 8204156 TI - Thrombolytic therapy for acute myocardial infarction: GUSTO criticized. PMID- 8204157 TI - Mortality from rabies in India. PMID- 8204158 TI - Lorenzo's oil and lymphocytopenia. PMID- 8204159 TI - Drapery cord injury and strangulation in babies. PMID- 8204160 TI - Frequency of EBV-DNA detection in Sjogren's syndrome. PMID- 8204161 TI - Nocturnal home oximetry in detecting the sleep apnea-hypopnea syndrome and in working up hypersomnolence. PMID- 8204162 TI - Management of breast cancer in southeast England. AB - OBJECTIVE: To examine the extent to which management of invasive breast cancer reflected consensus guidelines in the Thames regions in 1990. DESIGN: Population based study of case notes. SETTING: Thames Cancer Registry. SUBJECTS: All women with breast cancer diagnosed in early 1990 (417 cases) resident in the four Thames regions. Hospital records were traced for 346 cases, of which 12 were ineligible because of misclassification in initial registration and were excluded from the analysis. 334 cases were analysed. MAIN OUTCOME MEASURES: Investigations and treatment in the six months after diagnosis, stage of disease. RESULTS: Of the 334 women identified, 86 were aged under 50. Three years after diagnosis, 74 were dead, seven (8%) aged under 50 and 67 (27%) aged 50 or over. Axillary surgery was used to stage cancer in only 155 cases (46%), although this is recommended in the guidelines. Only 79 (24%) case notes had any information recorded on stage. Stage could be determined reliably for only half of the sample. Treatment varied widely within the same age group and stage of disease. In particular, chemotherapy was not routinely given to patients under 50 with stage II disease. Only 17 records showed evidence that the patient was participating in a clinical trial. CONCLUSIONS: There was a lack of consensus on the management of breast cancer among clinicians in 1990. More patients should be included in clinical trials. PMID- 8204163 TI - Foreign body reaction to suture material mimicking malignant microcalcifications in the breast. PMID- 8204164 TI - Outpatient management of fever in selected infants. PMID- 8204165 TI - Mercury exposure. PMID- 8204166 TI - Construction of a neoclitoris in male transsexuals. PMID- 8204167 TI - Competing modalities. PMID- 8204168 TI - A place for electronic fetal monitoring during labor. PMID- 8204169 TI - Another case of accidental pneumocephalus. PMID- 8204170 TI - Lung cancer and multiple exposures. PMID- 8204171 TI - Doctors and the Clinton plan. PMID- 8204172 TI - Doctors and the Clinton plan. PMID- 8204173 TI - The need for tort reform. PMID- 8204174 TI - Histological changes in venous grafts. PMID- 8204175 TI - Ceftriaxone for pediatric patients with Lyme disease. PMID- 8204176 TI - George Huntington: the man behind the eponym. PMID- 8204177 TI - Triggering of acute myocardial infarction by exercise. PMID- 8204178 TI - Gallium-67 imaging for thymic hyperplasia in adults following chemotherapy. PMID- 8204179 TI - Women's reproductive health. Family planning and AIDS prevention can be combined. PMID- 8204180 TI - Alcohol intake and mortality. PMID- 8204181 TI - Tubal ligation, hysterectomy, and risk of ovarian cancer. PMID- 8204182 TI - Money matters. PMID- 8204183 TI - Assessing tremor severity with long-term tremor recordings. PMID- 8204184 TI - Psoriatic arthritis with physical trauma. PMID- 8204185 TI - Nurse practitioners in primary care. PMID- 8204186 TI - Nurse practitioners in primary care. PMID- 8204187 TI - Sexual activity and contraceptive use amongst teenagers under the age of 15 years. AB - AIMS: The aims of this study were to document patterns of sexual activity and contraceptive use in a sample of 952 Christchurch born children studied to the age of 15 years. METHOD: Data on sexual activity and contraceptive use was collected on the basis of self report at ages 14 and 15 years. RESULTS: By the age of 15 years, 8.5% of this sample had engaged in sexual intercourse. Early sexual activity was more common amongst girls, amongst children of Maori or Pacific Island ethnicity and among children from families of unskilled or semi skilled socioeconomic status. Of those who were sexually active just under half (49.4%) reported having intercourse with only one partner while 17.3% (1.5% of the total sample) reported sexual experience with more than three partners by the age of 15 years. There was a high rate of contraceptive usage in the sample with 88.9% of those who were sexually active having used a recognised form of contraception and it was estimated that approximately 87% of sexual acts reported by this sample involved the use of contraception. The high rate of contraceptive usage for the sample was accounted for largely by the use of the condom and over 80% of those who were sexually active reported using this method. Despite the high rate of contraceptive usage evident for the sample just under one third of those who were sexually active reported having unprotected intercourse on at least one occasion. CONCLUSIONS: Bearing in mind the possibility of under reporting of sexual activity, the results suggest that by the age of 15 years in the region of 1 in 10 teenagers were sexually active. The major finding to emerge from the study was a high rate of utilisation of contraceptive methods, particularly the condom. It seems likely that this high rate of condom usage is a reflection of the effects of publicity and public education campaigns about the risks of HIV infection, AIDS and the need for safe sex. Despite the high rate of contraceptive usage for this sample it is suggested that those engaging in early sexual behaviour are a high risk population in need of support, assistance and counselling. PMID- 8204188 TI - The earliest signs of Alzheimer's disease. AB - Insufficient clarity of definition of the clinical features in the earliest stages of developing Alzheimer's disease (AD) has impeded the execution of clinical and biologic studies into this major public health problem. Defining the earliest signs of a disease with such an insidious onset can prove to be a most elusive task, particularly in a disease whose very nature renders the patients' self-report unreliable. We therefore administered a structured interview to the close family caregivers of 83 patients with probable AD, in order to investigate the earliest perceived signs of illness in the patients. In 44 (53%) of patients, the earliest objective sign of change was not memory impairment. The initial sign of change was of a psychiatric type in 27 (32.5%); of a neurologic type in nine (10.9%); and of a noncoping type in eight (9.6%). Such nonmemory signs, as perceived by caregivers, preceded objective memory impairment by a mean of 1.8 years. In 39 patients (47%), memory impairment was the initial perceived sign of illness. These findings suggest that the earliest clinical manifestations of AD may, in many cases, significantly predate objective signs of memory impairment. PMID- 8204189 TI - Depression in disabling illness: severity and patterns of self-reported symptoms in three groups. AB - The nature of association between depression and disabling illness, whether as an organic symptom or emotional consequence, has been the source of interest and controversy. Depression in three groups of medically ill, disabled patients (Parkinson's disease, right hemisphere stroke, and amputation) was studied. Mean depression severity and frequency of depression were equal for all groups. Severity of neurologic symptomatology was not consistently related to depression. Type of prosthesis, but not amputation type, was related to depression for amputees. Patterns of depression on discriminant analysis did differentiate the groups. A depression symptom conglomerate suggesting guilt and body image change with fatigue characterized the Parkinson patients most and the amputees least. A second depression conglomerate suggesting indecisiveness and thoughts of death or self-harm characterized amputees most and stroke patients least. Depression as an emotional response may not be a singular, specific feature of disabling illness in general, given uniformity of prevalence and severity, but differential etiology in specific instances should be considered. PMID- 8204190 TI - Clozapine in the elderly. AB - The authors reviewed the use of clozapine in eight patients over age 65 years with treatment-resistant psychoses. Six patients improved. Two patients became more confused. The authors suggest that clozapine be considered in treating elderly psychotic patients, and that its use need not be restricted to schizophrenic patients. PMID- 8204191 TI - Sleep in bereavement-related depression during and after pharmacotherapy with nortriptyline. AB - Our objective was to assess the effects of nortriptyline on electroencephalographic sleep and subjective sleep quality in spousally bereaved, depressed elders. Ten elderly volunteers with bereavement-related major depression had electroencephalographic sleep studies while depressed, after remission of depressive symptoms while still taking nortriptyline, and after nortriptyline discontinuation. Changes in sleep measures over time were compared both within bereaved subjects and with age- and sex-matched healthy controls. Remission of depressive symptoms while still on nortriptyline was associated with improvements in sleep quality (P < .002), rapid eye movement (REM) percent (P < .02), REM latency (P < .05), REM density (P < .05), and delta sleep ratio (P < .05). After discontinuation of nortriptyline, REM percent, REM latency, and delta ratio reverted to pretreatment levels, while sleep efficiency and sleep quality continued to show improvement coincident with sustained clinical remission. These data suggest that nortriptyline may be clinically useful in treating the sleep disturbance of elders with bereavement-related depression and that a double blind, placebo-controlled, randomized clinical trial is warranted. PMID- 8204192 TI - Factor structure and reliability of the Alzheimer's Disease Assessment Scale in a multicenter trial with linopirdine. AB - The Alzheimer's Disease Assessment Scale (ADAS) has assumed a primary role in assessment of treatment responses in large-scale multicenter trials of drugs being evaluated for treatment of dementia in elderly patients. Data from 280 patients with Alzheimer's disease were analyzed to evaluate factor structure and reliability. Results confirm the presence of three primary factors interpreted as mental status, verbal fluency, and praxis. The presence of a large general factor underlying those more specific dimensions also supports the utility of the composite ADAS cognitive score that has been used as a primary outcome measure in previous drug trials. Test-retest reliability of the factor scores were calculated to be 0.83, 0.78, and 0.87. Test-retest reliability of the composite ADAS cognitive score was 0.90. Statistics useful for estimation of sample sizes for future multicenter trials are provided. PMID- 8204193 TI - Late-life-onset panic disorder: clinical and demographic characteristics of a patient sample. AB - Although panic disorder is generally believed to begin in young adulthood, 13 cases of panic disorder with an initial onset after age 60 years have recently been seen at our clinics. Other than the time of life in which the first panic attack occurred, clinical and demographic profiles of these 13 patients were similar to those that have been reported for panic disorder patients whose panic began earlier in life. These findings indicate that panic disorder can affect older adults with no previous history of panic attacks, but further research is needed to determine the clinical and theoretical significance of late-life-onset panic disorder. PMID- 8204194 TI - Neurologic diseases presenting with gait impairment in the elderly. AB - We conducted a prospective study to evaluate the underlying diseases and their frequencies in 50 consecutive patients older than 50 years of age admitted to our neurologic service because of walking difficulty. The diseases identified in our study were as follows: multiple cerebral infarcts, 24%; myelopathy, 22%; parkinsonism, 12%; cerebellar degeneration, 8%; other diseases, 24%; and unknown etiology, 10%. Potentially treatable causes of gait impairment were found in nearly one third of patients. PMID- 8204195 TI - The evaluation of behavioral disturbances in Alzheimer's disease: the utility of three rating scales. AB - Behavioral disturbances, eg, wandering, irritability, depression, and delusions, are observed in Alzheimer's disease (AD). Determining the importance of such symptoms requires that they be evaluated objectively. The Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD), Cornell Scale for Depression in Dementia (Cornell), and Brief Psychiatric Rating Scale (BPRS) were administered to 61 AD and 20 elderly control subjects. Only one AD subject showed no behavioral symptoms. All scales were reliably rated for presence or absence of symptoms. However, assessment of reliability of severity ratings was limited, because symptom frequency and severity were low. Although the Cornell and Behave AD appeared more appropriate for AD subjects than did the BPRS, neither scale provided a complete description of behavioral symptoms, and each showed problems that interfere with its use. We recommend the development of a comprehensive scale with a well-anchored system of scaling and detailed rater instructions. PMID- 8204196 TI - Ethanol acutely reduces LH and prolactin secretion: possible involvement by dopamine. AB - Ethanol (ETOH) administered acutely to castrate male rats caused a decline in pituitary luteinizing hormone (LH) and prolactin (PRL) secretion. This was associated with an elevation in hypothalamic and median eminence stores of dopamine (DA) that was related to the dose of alcohol given. Pituitary stalk transection (PST) resulted in a significant rise in plasma PRL levels compared to sham control animals, which suggests that DA in the hypophysial portal blood exerted an inhibitory influence on pituitary PRL secretion. The DA agonist bromocriptine failed to alter mean plasma LH levels in stalk-transected rats. The ETOH-treated castrated rats showed a significant rise in circulating PRL after injection of the DA receptor antagonist haloperidol metabolite II (HAL), but the administration of the DA receptor agonist R(-)-apomorphine HCL (APO) caused plasma PRL to decline to near undetectable levels. Plasma LH levels remained unchanged in the HAL- and APO-treated rats and were similar to those of sham controls. These results suggest that lactotroph DA receptors were still functional. Thus our previous finding of ETOH-induced reduction on LH secretion may be attributable to an inhibitory effect by DA on the luteinizing hormone releasing hormone (LHRH) peptidergic neurons rather than a direct inhibition by DA on the pituitary gonadotroph. PMID- 8204197 TI - Does a relationship exist between the quality of stress and the motivation to ingest alcohol? AB - Previous experimental findings on the relationship between emotional stress and motivation to ingest alcohol are contradictory. To obtain information about this relationship we tested the effects on alcohol consumption in rats subjected to two types of chronic unavoidable stressors, intermittent immobilization and social isolation, which differ in their influence on the functional state of the endogenous opioid system. To characterize the nature and magnitude of the stress induced by these stressors, we measured their effects on functional parameters which have a close relationship to the regulatory influence of endogenous opioid peptides (endogenous opioid dependence, pain sensitivity, blood pressure). Our investigations have shown that chronic intermittent immobilization, which induced development of endogenous opioid dependence, presumably due to activation of endogenous opioid systems, did not produce increased alcohol consumption. On the contrary, chronic social isolation, which did not induce development of endogenous opioid dependence, was followed by a significant increase in alcohol consumption. It is concluded that not all types of stress produce increased alcohol consumption, but that the effect on the endogenous opioid system may be a decisive factor in determining whether a stressor produces increased alcohol consumption. PMID- 8204198 TI - Desmethionine-bombesin receptor antagonist blocks bombesin-induced inhibition of alcohol intake. AB - [D-Phe6,Des-Met14]bombesin(6-14), ethyl amide (D-BN) is a specific, competitive receptor antagonist of bombesin, a neuropeptide that inhibits alcohol and food intake. We tested the effects of IP injected D-BN (4-400 micrograms/kg) on bombesin-induced (4 micrograms/kg) reduction of caloric intake. In the first experiment, ad lib-fed female and male rats (Ns = 18) were deprived of water for 23 h, injected with peptides or saline in randomized sequences of doses, and immediately given access to 5% w/v ethanol for 30 min, followed by 30 min of water. In a second experiment, male rats (N = 10) were injected with the antagonist at 10 or 20 min prior to bombesin injection and alcohol access, and behaviors were observed and quantified once a minute with an instantaneous time sampling technique. D-BN injection blocked the bombesin-induced reduction in alcohol intake (> or = 40 micrograms/kg) and food intake (> or = 200 micrograms/kg). When injected 20 min prior to access, D-BN alone (200 micrograms/kg) initially elevated alcohol drinking and later increased feeding behaviors and decreased resting, relative to saline injection. Results indicate bombesin-induced reduction of alcohol intake depends on a specific peptidergic receptor process, and endogenous bombesin-like peptide could act physiologically to elicit satiation with ethanol and food. PMID- 8204199 TI - Differential activating effects of ethanol in C57BL/6Abg and DBA/2Abg mice. AB - A characteristic pattern of ETOH-induced locomotor activation in the DBA/2Abg strain (D2), small activation or sedation in the C57BL/6Abg (B6), and an intermediate position of the F1s was found using a between-group design and 1.5 g/kg ETOH. This pattern was consistent for a variety of behavioral indices not previously examined, including distance, rest time, movement speed and length, as well as the traditional horizontal counts. Using a within-subject, multiple day, repeated-testing procedure, the same three genotypes were also assessed after manipulating drug administration order, where ETOH exposure (1.5 g/kg) was on either the first or second test day. Another experiment examined the effect of lighting level on the response to 1.5 g/kg ETOH using a within-subjects approach. Neither the testing order nor lighting condition had any major influence on the magnitude of activation as measured by locomotor activity (distance). The pattern of additive genotypic influences exhibited by the B6, D2, and F1 mice is remarkably resistant to these contextual and procedural manipulations. PMID- 8204200 TI - Ethanol reinforcement and its relationship to saccharin preference in Wistar rats. AB - Forty rats were given a choice between 0.1% sodium saccharin and water. Based on their intakes, three groups of six rats representing high, intermediate, and low saccharin preferences were selected. These rats were reduced to 80% of their free feeding weights. Ethanol was established as a reinforcer by use of a food-induced drinking procedure. Between-group differences were assessed based on response rates across acquisition sessions (0, 1, 2, 4, 5.7, 8%, w/v), a fixed-ratio series (1, 2, 4, 8, 1), and a concentration series (8, 5.7, 4, 2, 2, 4, 5.7, 8, 11.3, 16, 22.6, 32, 8%, w/v). In 29 of 32 conditions which were analyzed, the mean number of responses for ethanol was higher for the high saccharin preference group than for the low, and in 25 of 32 conditions, the intermediate group fell between the high and the low. However, there was considerable variability within groups across all conditions, such that mean between-group differences were not significant. This variability may be reduced by considering diet preferences in addition to saccharin preference. Nonetheless, these results offer limited support for the increasing body of evidence indicating a relationship between the factors mediating ethanol self-administration and those involving ingestion of palatable foods and fluids. PMID- 8204201 TI - Developing rat Purkinje cells are more vulnerable to alcohol-induced depletion during differentiation than during neurogenesis. AB - This study compared the extent of cerebellar Purkinje cell depletion induced by administering alcohol to rats during two temporally distinct periods of Purkinje cell development--neurogenesis and early differentiation. One group received alcohol (5 g/kg/day) during and shortly after Purkinje cell neurogenesis (gestational days 13-18) via oral intubation of pregnant dams. A second group received alcohol (2.5 g/kg/day) during early Purkinje cell differentiation (postnatal days 4-9) via artificial rearing of pups. The two alcohol treatment protocols were designed to match the cyclic daily blood alcohol profiles of the two groups as closely as possible. Pair-fed intubated controls, artificially reared gastrostomy controls, and normally reared ad lib/suckle controls were also evaluated. Mean peak blood alcohol concentrations (BACs) were 266 mg/dl for the intubated pregnant dams and 205 mg/dl for the pups exposed postnatally. Purkinje cell profiles were counted from single, 2-microns-thick midsaggital sections on postnatal day 10. Alcohol exposure during neurogenesis resulted in no significant change in Purkinje cell profile densities. Exposure during differentiation produced significant reductions in Purkinje cell profile densities, predominantly in the early maturing regions of the vermis (lobules I-IV and IX-X). These results indicate that Purkinje cells are more vulnerable to alcohol-induced population depletion during differentiation than during neurogenesis. PMID- 8204202 TI - 5-HT1A receptor agonists reduce ethanol-induced locomotor activity in mice. AB - Animal studies as well as clinical studies have suggested that the brain 5-HT system is important for the regulation of voluntary ethanol intake and preference. Previous studies have suggested that 5-HT1A receptor agonists may reduce ethanol preference in rats. In the present study on mice, the 5-HT1A receptor agonists (8-OH-DPAT), ipsapirone, and buspirone all antagonized the locomotor activity (LMA) stimulatory effect of ethanol (2.5 g/kg). The present results provide further support for the notion that the LMA-increasing effect of ethanol may be homologous to its reinforcing properties and that 5-HT1A receptor agonists may counteract these properties as well. PMID- 8204203 TI - Sham intake of ethanol in "P" rats. AB - Alcohol-preferring (P) rats were surgically fitted with gastric fistulas, and intakes of 10% ethanol solution were measured in 1-h sessions either with the fistula closed (normal drinking) or open (sham drinking). In water-replete P rats in which ethanol access was limited to 1 h/day, no increase in intake was noted in the sham compared with normal drinking tests in the day. A small increase was seen when the sham drinking test was conducted at night. In water-deprived P rats, sham intake of ethanol was elevated over intakes in closed fistula trials. However, in comparison with water intake on separate test days, sham intake of ethanol by P rats was lower and satiated after 15-30 min. The absence of robust sham alcohol drinking in P rats is similar to what we have previously reported in normal Sprague-Dawley rats, suggesting that preabsorptive factors alone do not account for the strain differences in ethanol preference. PMID- 8204204 TI - Genotype regulates the development of tolerance to ethanol and cross-tolerance to nicotine. AB - The long-sleep (LS) and short-sleep (SS) mouse lines were selectively bred for differential sensitivity to the anesthetic actions of ethanol, but they also differ in sensitivity to nicotine. A recent study suggested that the LS mice develop more tolerance to ethanol and cross-tolerance to nicotine than do the SS following chronic ethanol treatment. The studies reported here expand on these previous studies by assessing potential tolerance to ethanol and cross-tolerance to nicotine using additional behavioral and physiological measures. In addition, the effects of chronic ethanol treatment on ethanol and nicotine metabolism were measured. The LS mice developed tolerance to ethanol as measured by effects on open-field activity, body temperature, and sleep time, whereas the SS mice did not develop consistent tolerance to ethanol's effects on any of these measures. Cross-tolerance to nicotine's effects on open-field activity and body temperature developed, but only in the LS mice. The ethanol tolerance is likely due to changes in CNS sensitivity to ethanol, but altered elimination of nicotine may explain much of the cross-tolerance to nicotine seen in chronic ethanol-treated LS mice. PMID- 8204205 TI - Effect of ethanol on the interaction between the macrophage and Mycobacterium avium. AB - Chronic ethanol ingestion predisposes to tuberculosis and bacterial pneumonia. Mycobacterium avium complex organisms cause bacteremia in patients with AIDS. Human macrophages and murine Kupffer cells exposed to ethanol are more permissive towards intracellular growth of M. avium than control mononuclear phagocytes. Ethanol also has been shown to impair the ability of human macrophages and murine Kupffer cells to respond to stimulation with tumor necrosis factor (TNF) and granulocyte macrophage colony stimulating factor (GM-CSF), and to produce cytokines such as interleukin-1, interleukin-6, and TNF when properly stimulated. The impairment is dependent in part on a downregulation in the number of TNF receptors on the macrophage's membrane. Recent evidence suggests that ethanol in nonlethal concentrations induces stress-related proteins in M. avium, leading to the inhibition of intracellular pathways in the macrophage and, consequently, impairing some of its functions. In summary, ethanol acts both on the host and on the mycobacterium in a complex sequence of events that influence the outcome of the infection. PMID- 8204206 TI - Ethanol, immune responses, and murine AIDS: the role of vitamin E as an immunostimulant and antioxidant. AB - Excessive alcohol consumption is a major health problem in the United States. Prolonged consumption of alcohol results in alterations of immune responses, ultimately manifested by increasing susceptibility to infectious agents. Such changes can be due to the direct effects of alcohol or its metabolites on immune cells, as well as to nutritional deficiency, oxidative stress, and neutrophil dysfunctions. This ETOH-induced immunosuppression could be a potential cofactor in the progression to AIDS. As vitamin E supplementation has been associated with enhancement of immune response and improvement of host defense, it may provide a useful therapeutic approach for treatment of alcoholics to improve host defense. This article is a review of alcohol-related immunosuppression as a possible cofactor in the development of AIDS, and vitamin E-related immunoenhancing roles in animals and humans, showing why vitamin E supplementation could be used as a useful adjunct agent in alcoholics' treatment. Since there is little information available regarding nutritional therapy with alcohol users, our purpose is to provide evidence from animal models of the potential therapeutic role of vitamin E supplementation in the treatment of alcoholics. PMID- 8204207 TI - Selective effect of alcohol on cellular immune responses of lymphocytes from AIDS patients. AB - In this study we examined the in vitro effects of alcohol on the proliferative responses of lymphocytes from healthy donors and AIDS patients to a recombinant fusion peptide, env-gag, corresponding to portions of the gp41 envelope (env) and internal core (gag) proteins of HIV. The effects of alcohol (ETOH) on the natural killer (NK) cell activities of lymphocytes from healthy donors and patients with AIDS were also investigated. Peripheral blood mononuclear cells from both normal donors and AIDS patients produced significant levels of lymphocyte proliferative responses to the HIV env-gag peptide; however, these responses were significantly higher in patients with AIDS, showing the specificity of the response. The env gag-induced proliferative responses of lymphocytes from normal subjects were significantly suppressed when cultures contained only higher levels of ETOH (0.2% and 0.3%), whereas ETOH even at a lower level (0.1%) produced significant suppression of the env-gag-induced proliferation of lymphocytes only from AIDS patients. Direct addition of ETOH at concentrations of 0.1%, 0.2%, and 0.3% to cultures of lymphocytes from normal donors and NK target cells did not produce significant suppression of NK cell activities. However, ETOH at concentrations of 0.2% and 0.3% significantly suppressed the NK activities of lymphocytes from AIDS patients, and the suppressive effect was observed at all E:T cell ratios examined. Control peptide from the Escherichia coli expression vector did not produce any significant effect on lymphocyte proliferative responses or NK activity of both normal donors and AIDS patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204208 TI - Human studies on alcohol and susceptibility to HIV infection. AB - Here we review existing evidence that alcohol intake may influence the susceptibility to human immunodeficiency virus type 1 (HIV-1) infection and the effect that alcohol may have on accelerating the onset of AIDS after the initial infection. Possible immunological and psychosocial mechanisms to explain the increased incidence of HIV-1 infection in alcoholism are discussed. PMID- 8204209 TI - Effect of 5-methylcytosine on the structure and stability of DNA. Formation of triple-stranded concatenamers by overlapping oligonucleotides. AB - A triple helix can be formed upon binding of a pyrimidine oligonucleotide to the major groove of a homopurine-homopyrimidine (R.Y) double-stranded DNA target site. Here, we report that this reaction can be influenced by base methylation. The pyrimidine strand 5'-TmCTmCTmCTmCTTmCT (mY12), whose cytosine residues are methylated at C5, does not bind the duplex 5'-AGAGAGAGAAGA.3'-TCTCTCTCTTCT (R12.Y12) to yield a 12-triad triplex, as would be expected from these DNA sequences. Rather, a complex of overlapping oligonucleotides, which we define concatenamer, is formed. The concatenamer is clearly evidenced by polyacrylamide gel electrophoresis (PAGE) since it migrates with a smeared band of very low mobility. The stoichiometry of the concatenamer, determined by both UV mixing curves and electrophoresis, is surprisingly found to be (R12.2mY12)n, thus showing that the unmethylated Y12 strand is excluded from the complex. Denaturation experiments performed by ultraviolet absorbance (UV) and differential scanning calorimetry (DSC) show that the concatenamers melt with a single and highly cooperative transition whose Tm strongly depends on pH. Overall, the data point to the conclusion that the concatenamers are in triple helix, where the methylated mY12 strand is engaged in both Watson-Crick and Hoogsteen base pairings, thus displacing the Y12 strand from the R12.Y12 duplex. A possible mechanism of concatenamer formation is proposed. The results presented in this paper show that 5-methylcytosine brings about a strong stabilizing effect on both double and triple DNA helices, and that pyrimidine oligonucleotides containing 5-methylcytosine can displace from R.Y duplexes the analogous non methylated strand. The advantage of using methylated oligonucleotides in antisense technology is discussed. PMID- 8204210 TI - Reversible crystal transition of guanosine between the dihydrate and anhydrous states coupled with adsorption-desorption process. AB - Relative humidity induces the reversible crystal transition of guanosine between the dihydrate and the anhydrous state. The characteristics of the transition was investigated by means of X-ray powder diffraction analysis and high-resolution solid-state 13C NMR spectroscopy. Adsorption-desorption hysteresis was observed. Guanosine dihydrate (the H-state) which is crystallized from an aqueous solution rapidly loses crystal water below 10% relative humidity (rh), and is anhydrous at 0% rh (the A-state). The crystals gradually recover the H-state at approximate 20% rh. In the adsorption process between 10-20% rh, there exists one intermediate state, M, with 1.2-1.3 moles water per mole guanosine. The lattice of the M-state was determined to be orthorhombic with the cell parameters of a = 16.248(1), b = 11.603(1), and c = 13.643(2) A. The base-stacking structure is retained throughout the transition. On the other hand, conformational changes of the riboses and break of the hydrogen-bonding network between the bases would be induced in the A-state in conformity with lack of crystal water. PMID- 8204211 TI - Probing conformational isomerizations of double-stranded poly(dA-dT) by a substitution of minor amounts of the thymine methyls with bulky hydrophobic isopropyl groups. AB - We probed conformational polymorphism of a synthetic DNA poly(dA-dT) by introducing various small amounts of bulky spherical hydrophobic isopropyl groups into the polynucleotide primary structure. For this purpose, three mixed copolymers of poly(dA-dT,ip5dU) were synthesized in which 2.6%, 8.6% or 14.2% of the polynucleotide pyrimidine bases had the isopropyl group in position 5. The isopropyls made the formation of both A-form and X-form incomplete, and this effect increased with the increasing isopropyl amount in the polynucleotide. However, the polynucleotide isomerization into the A-form was hindered by the isopropyls while the isomerization into the X-form was rather promoted. This observation indicates that, unlike the A-form, the X-form has the base pairs shifted towards the double helix major groove. Z-form was also promoted by the lowest concentration of the isopropyl groups while the most isopropylated poly(dA dT) aggregated under the Z-form inducing conditions. PMID- 8204212 TI - Sequence-dependent conformational variations in the B-DNA double-helix of poly d(AATT).poly d(AATT). AB - X-ray diffraction data from well oriented and polycrystalline fibers of the lithium salt of poly d(AATT).poly d(AATT) are isomorphous with those from B-DNA. The double-helix consists of conformationally identical antiparallel strands and the molecular symmetry is 2 5(2); the asymmetric unit is a tetranucleotide, AATT, and 5 tetranucleotides span two turns per strand. Two double helices pass through a monoclinic unit cell of dimensions a = 31.05, b = 22.62, c = 33.85 A (fiber axis) and gamma = 90 degrees. In each repeating motif, the four nucleotides have distinct conformations, TpA displays an axial P-O bond and there is shortening of minor groove in the central region. PMID- 8204213 TI - Z curves, an intutive tool for visualizing and analyzing the DNA sequences. AB - A novel method mapping the DNA or RNA sequence into a folding curve in three dimensional space, the Z curve, has been proposed based on the symmetry of the regular tetrahedrons. There exists a unique Z curve for a given DNA sequence, on the contrary, the DNA sequence can be uniquely determined by the given Z curve. The properties of the Z curves have been studied in great details. The symmetry, the periodicity, the local motif, and the global feather of the distribution of bases of the DNA sequences are reflected by the rich folding structures of the Z curves. The Z curves may be smoothed by the B-spline functions of different orders. Therefore, the Z curves may have any resolution by choosing the suitable spline functions. The higher the order of the B-spline function chosen, the lower the resolution of the Z curve. So, the Z curves are suitable for visualizing and analyzing the DNA sequences with any length. The study of the Z curves develops further a new area to visualizing and analyzing the DNA sequences by a geometrical approach. The method of the Z curves may be strengthened by using the ripe mathematical tools of geometry on the one hand; and by using the powerful technique of the computer graphics on the other hand. PMID- 8204214 TI - Dissociation of duplexes formed by hybridization of DNA with gel-immobilized oligonucleotides. AB - The method of DNA sequencing by hybridization with oligonucleotides matrix (SHOM) developed in this laboratory (1.2) uses the matrix of oligonucleotides immobilized within polyacrylamide gel. The particular feature of this matrix is that the apparent thermostability of the duplexes depends on the concentration of gel-immobilized oligonucleotides. This dependence is specific for oligonucleotides immobilized in the gel volume (3-D-immobilization) rather than on a flat surface of a filter or glass (2-D-immobilization). The theory has been developed that provides a quantitative description of temperature-dependent duplex dissociation within gel. The theory takes into account that the diffusion of dissociated DNA out of the gel is retarded by multiple acts of association dissociation of DNA with immobilized oligonucleotides. It allows to calculate the apparent dissociation temperature of duplexes and describes quantitatively its growth upon increase in the enthalpy of duplex dissociation, concentration of immobilized oligonucleotides, gel thickness and decrease of dissociation entropy and washing time. Concentration of gel-immobilized oligonucleotides can be calculated for a normalized matrix in which GC-rich and AT-rich duplexes exhibit the same apparent thermostabilities and are washed off at the same temperature. This simplifies identification of perfect duplexes formed on the matrix which can be carried out for all duplexes at the same temperature. The gel-immobilized oligonucleotide matrix provides also a higher capacity for immobilization and therefore a higher sensitivity of measurements, resulting in a higher discrimination power for identification of perfect duplexes as compared with matrixes of oligonucleotides immobilized on a surface. PMID- 8204215 TI - DNA sequencing by hybridization to oligonucleotide matrix. Calculation of continuous stacking hybridization efficiency. AB - In this paper we consider the efficiency of additional rounds of "continuous stacking" hybridization in DNA sequence reconstruction by hybridization with oligonucleotide matrix (SHOM). After the initial hybridization of target DNA with the matrix of oligonucleotides of fixed length L some additional hybridizations should be carried out in the presence of fluorescently labeled oligonucleotides of another length l. These additional oligonucleotides can hybridize in tandem with matrix tuples (continuous stacking hybridization) thus forming an extended duplex with the target DNA strand. The additional data obtained allows resolutions of branching points arising in the reconstruction procedure. Multiple rounds of continuous stacking hybridization considerably increase the efficiency of the sequencing method, eventually approaching the power of (L+l)-matrix. We develop here an algorithm that allows us to minimize the number of additional hybridization steps, by assembling sets of l-tuples to be added together in each round of continuous stacking hybridization. For SHOM using a matrix of octanucleotides, continuous stacking hybridization with pentanucleotides increases the length of unambiguously sequenced DNA from 200 to several thousands of base pairs. PMID- 8204216 TI - The 30 nm chromatin fiber as a flexible polymer. AB - Our analysis of the data of van den Engh, Sachs, and Trask (Science 257, 1410 (1992)), for the dependence of the mean square distance between pairs of hybridization sites (< L2n >, micron 2) on the known genomic distance (n, bp) separating these sites on chromosome number 4 in G1 human fibroblast nuclei, shows that < L2n > is proportional to n2v with v = 3/5 for n < 1 Mbp. The v-value of 3/5 is characteristic of flexible polymer chains with excluded volume effects in dilute good solutions. Since the DNA concentration in nuclei is very high (ca. 1-10 mg/ml), and theory (Flory, J. Chem. Phys. 17, 303, 1949) predicts v = 1/2 for overlapping polymers, the finding of v = 3/5 means that the chromatin fibers do not overlap in interphase nuclei. The dependence of < L2n > on n for n < 4 Mbp is consistent with the model of large (approximately 6 Mbp, 3 microns diameter) loops of interphase chromatin attached to nuclear membrane sites. Using the constant (e.g., Widom, Ann. Rev. Biophys. Biophys. Chem. 18, 365 (1989)) and variable (Williams & Langmore, Biophys. J. 59, 606 (1991)) diameter fiber models, the Kuhn statistical segment of the 30 nm chromatin fiber was estimated to have a length of 196-272 nm with a corresponding DNA content of 21-37 kbp.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204217 TI - Structure and self assembly of a retrovirus (FeLV) proline rich neutralization domain. AB - The 60 amino acid proline-rich neutralization domain of the external surface unit glycoprotein of feline leukemia virus was chemically synthesized in total and in fragments. We examined the ability of these retroviral peptides to form ordered conformations using 1H-NMR, circular dichroism spectroscopy, and intrinsic viscosity measurements. One dimensional nuclear magnetic resonance spectroscopy revealed that the 60 amino acid peptide could form a stable, folded structure that was long-lived, as shown by the ability to protect amide-protons in D20. Peptides corresponding to the N-terminal 42, N-terminal 20 amino acids, and middle 20 amino acid sections could also form stable structures. The C-terminal segment did not protect any protons in D20. Interestingly, self assembly of the N terminal 42 and C-terminal 16 amino acid peptides into a structure very close to that of the 60 amino acid domain was observed. The circular dichroism results reveals a large negative cotton effect at 198 nm that is characteristic of the proline-rich beta-turn helixes which consist predominantly of trans-proline. The intrinsic viscosity results suggest a non-random coil structure that is rod shaped. Our conclusion is that PRN60 forms a beta-turn helix and that this region of FeLV-gp70 is a separate folding domain of the retroviral surface unit glycoprotein. The unique conformational properties of PRN60 and its critical role as the predominant target for neutralizing antibody responses suggest that this peptide is a reasonable candidate for producing a synthetic peptide vaccine for FeLV. PMID- 8204218 TI - Computer-assisted predictions of the secondary structure in the plant virus single-stranded DNA genome. AB - Coconut foliar decay virus (CFDV) contains the single-stranded circular DNA molecules of 1291 nucleotides which were found to replicate autonomously in the cells of the diseased palms. The special features of the CFDV DNA sequence, including putative secondary structure and the distribution of the inverted repeat motifs, are investigated with computer-assisted prediction methods. It is evident that the structural principle of the branched series of long and short double helixes interspersed by short non-helical regions is existed for CFDV virion DNA. The total degree of base pairing is near 62%. We have also predicted the presence of several sequence elements formed by inverted repeat motifs which are potentially capable of binding the eukaryotic transcriptional regulatory factors. PMID- 8204219 TI - A study of the interaction of DAPI with DNA containing AT and non-AT sequences- molecular specificity of minor groove binding drugs. AB - The binding specificity of DAPI to DNA has been probed by analysing its interactions with DNA octamers consisting of different base sequences, which include adenine, guanine, 2-amino adenine and inosine, using molecular mechanics methods. Presence of AT and non-AT base pairs in the immediate vicinity of the binding site, containing AT and non-AT base pairs is also investigated. Results show that DAPI most prefers to bind to homopolymer of AT, and least to the duplex containing alternating GC bases. DAPI interacts with homopolymeric duplexes in two possible orientations related by 180 degrees with nearly same affinity. Affinity of DAPI towards DNA comprising the modified bases, inosine and 2-amino adenine, is in between these extremities. The binding affinity is reduced to some extent by the occurrence of non AT bases flanking the four base paired binding region. An interesting revelation is that one can visualise DAPI to form a hydrogen bond with O2 of cytosine indicating that the 2-amino group of purines does not per se sterically preclude DAPI from residing in the minor groove of B DNA helix. On the other hand, repulsive nature of electrostatic interactions that prevail at the minor groove consequent to the presence of these sequences contribute decisively in preventing further diffusion of the drug. Thus, electrostatics, rather than hydrogen bonding to bases, seemingly play an important role in determining the specificity of interaction. The retention of drug binders in the minor groove and therefore recognition, is governed by the combined effect of these various forces. PMID- 8204220 TI - An empirical potential study of the interaction of L-lysine-L-alanine-L-alanine tripeptide with four models of B-DNA with different compositions. AB - The empirical potential including the intra- and intermolecular energy terms was used to study the interaction of L-Lysine-L-Alanine-L-Alanine Tripeptide with four models of B-DNA with different compositions. On the basis of a detailed search of the respective potential energy surface, it was found that the peptide is preferentially bounded to the AT-rich sequences. Analysis of the different energy contributions indicated that the electrostatic term is responsible for this preference. The results agree with the experimental data on the selectivity of some DNA--binding proteins and polypeptides to AT-rich DNA. PMID- 8204221 TI - Interaction of two peptide-acridine conjugates containing the SPKK peptide motif with DNA and chromatin. AB - The interaction between DNA and two peptide-acridine conjugates containing one (1) or two (2) moieties of the Ser-Pro-Lys-Lys (SPKK) minor groove-binding peptide motif has been studied by a combination of hydrodynamic, biochemical and spectroscopic methods including diffusion-enhanced luminescence energy transfer (DELET) measurements with a Tb(III) lanthanide chelate as donor. Viscometric titrations do not reveal any significant difference between the two hybrid molecules which both unwind (by about 15 degrees) and extend the DNA similarly. DELET measurements show that the acridinyl chromophore of compounds 1 and 2 is much more accessible than that of a simple monointercalating drug such as acridine orange or ethidium. The accessibility factor increases proportionally with the peptide length, reflecting the extent of perturbation imposed upon the intercalating chromophore by the binding to DNA of the peptide moiety of the hybrids. Experiments with the osmium tetroxide-bispyridine reagent indicate that the two hybrid compounds both affect the local conformation of DNA rendering certain thymine residues conspicuously accessible to the probe. The drug-induced sites of hyperreactivity towards OsO4 in DNA are very similar with the exception of a short run of three T residues which is attacked more strongly in the presence of tetrapeptide-acridine conjugate 1 than with the octapeptide-acridine conjugate 2. These results are fully in agreement with previous footprinting studies and support the view that a minimum of two SPKK motifs is required to mimic the AT-specific minor groove binding antibiotic netropsin. On the basis of the DNA-binding properties of these two peptide-acridine hybrids, we present DNA binding models in which the acridinyl moiety of compound 1 protrudes slightly outside the double helix but remains more or less parallel to the plane of the base-pairs. In contrast, with compound 2, where the octapeptide SPKKSPKK is bound to the minor groove, we postulate that the chromophore lies only partially overlapped with the base pairs in the intercalation site and, in addition, the heterocyclic chromophore is significantly tilted with respect to the double helix axis. Electric linear dichroism and DELET measurements with chromatin reveal that the presence of histone proteins affects the intercalative binding of compound 2 while it has practically no effect on the binding of compound 1. PMID- 8204222 TI - [Voluntary rehabilitation during the license suspension period--a model trial in Hessen]. AB - Based on an analysis of the specific psychological situation of drink drive offenders, a concept of integrated counselling and retraining that is currently being tested in Hesse/Germany will be presented. According to experiences from medico-psychological tests as well as counselling and retraining, the period of suspension after revoking a driver's license is but a security measure in the legal sense that does not necessarily result in an change in the offender's attitude. The course-model FRS (Freiwillige Rehabilitation in der Sperrfrist- Voluntary Rehabilitation during Suspension) will be presented describing its conditions of development, its content, and its procedure along with the results and experiences so far obtained. PMID- 8204223 TI - [Effect of low dose alcohol concentration on saccadic eye movements. Infrared reflection technique for recording oculomotor reactions with reference to dangerous traffic situations]. AB - Saccadic eye movements were registered under different ethanol concentrations (0 g/kg, 0.5 g/kg, 1.0 g/kg) using an infrared reflexion method. On the basis of photographic pictures conflict situations of a car driver were simulated. 12 young car drivers were exposed for 10 sec to four pictures, all under different ethanol concentrations. The eye movements were registered and analyzed by a computer. The amplitude of saccades, their number, duration and velocity as well as the points of fixation and the scanning of the pictures were qualitatively and quantitatively analyzed. All persons demonstrated deficits in all parameters under 1 g/kg blood ethanol concentration. Nearly all results were reduced under 0.5 g/kg in comparison to 0 g/kg situation. In conclusion, low dose ethanol influence the saccadic eye movements. On the other hand the study could demonstrate a new technique (infrared reflexion technique), which allows the qualitative and quantitative recording of the influence of ethanol as well as peripheral as cortical structures of the brain. The exposition to photographic pictures demonstrating dangerous traffic situations simulate real traffic situations and allows to transfer the laboratory results to real situations. PMID- 8204224 TI - [Ethanol content of Kefir water]. AB - The question of the influence of kefir on blood-alcohol-level has been asked in a legal proceeding. The questioned recipe consisted of 21 water, 6 soup-spoons of kefir granules (about 120 g), 150 g sugar, 2 figs and one lemon. The consumption took place after two days of fermentation. Experimentally we found, that one liter of this kefir product may contain up to 38 g/l ethanol after 7 to 10 days. On the second day we measured up to 16 g/l ethanol. Our results may be import for expert appraisements concerning unability of driving. PMID- 8204225 TI - [Appropriate procedure with suspected intoxicated drivers--a discussion of recent theories on diagnosis and rehabilitation]. AB - Within the last couple of years a dramatic change of judging the drinking driver has taken place having serious consequences for the individuals involved. Many DWI offenders are forced to abstain from any alcoholic beverage though characteristics of personality as well as of offence indicate that rehabilitation by participation in an intervention program may result in the same reduction of relapse probability as for a comparable group of drivers in the years before. The changed reflection is mainly caused by a superficial overestimation of blood alcohol concentration (BAC) figures found at the time of event. There is a tendency to regard BAC values as unquestionable indications of addiction. In particular the numerous publications by Stephan, who decisively has influenced the rigorous judgement of drinking drivers, are typical of using a static view of drinking habits that does not describe the actual drinking patterns of the problem drinker. Therefore, a dynamic view is discussed. Furthermore, a critical acknowledgement of findings is carried out for those drinking experiments that have been a contribution to the change of opinions. The authors finally refer to the necessity of therapeutic interventions which in comparison to imposed abstinence proved to reduce relapse probability. PMID- 8204226 TI - [Doubt about alcohol "enjoyment"? Some critical comments on the contribution by Goetze et a. in this issue]. PMID- 8204227 TI - Intravenous ketorolac as an adjuvant to pediatric patient-controlled analgesia with morphine. AB - STUDY OBJECTIVE: To assess the effects of a single intraoperative dose of intravenous (i.v.) ketorolac on postoperative opioid dose requirements, quality of analgesia as assessed by the patient, and frequency of opioid-related side effects during pediatric patient-controlled analgesia (PCA) with morphine. DESIGN: Prospective, randomized, double-blind study. SETTING: Operating rooms, postanesthesia care unit (PACU), and inpatient care units of a freestanding children's hospital. PATIENTS: 50 ASA physical status I-II orthopedic surgical patients ages 8 to 16 years. INTERVENTIONS: Either 0.8 mg/kg of i.v. ketorolac or no additional analgesic was administered at the time of wound closure. After surgery, all patients were placed on PCA with morphine. MEASUREMENTS AND MAIN RESULTS: Individual morphine use during the first 12 hours of PCA therapy was recorded. A visual analog scale (VAS) pain score was obtained from the patient at the time of discharge from the PACU and at 4, 8, and 12 hours postoperatively. Any vomiting, pruritus, or urinary retention occurring during the first 12 postoperative hours was noted. The morphine plus ketorolac group administered significantly less PCA with morphine during the first 12 postoperative hours than did the morphine only group (p = 0.002). The morphine plus ketorolac group also reported significantly lower overall VAS pain scores (p < 0.01). Although similar frequencies of vomiting and pruritus were observed, the morphine plus ketorolac group experienced significantly less urinary retention than did the morphine group (p = 0.02). CONCLUSION: A single intraoperative dose of i.v. ketorolac appears to be opioid dose sharing, to provide superior analgesia, and to decrease the frequency of urinary retention during the first 12 hours of postoperative pediatric PCA with morphine. PMID- 8204228 TI - Calcium channel blockers do not enhance increases in plasma potassium after succinylcholine in humans. AB - STUDY OBJECTIVE: To determine whether chronic calcium channel blocker therapy exaggerates the rise in plasma potassium concentration ([K+]) after succinylcholine administration. DESIGN: Prospective clinical study. SETTING: University and Veterans Affairs hospitals. PATIENTS: 36 ASA physical status III and IV male patients: 21 patients taking chronic calcium channel blockers and 15 patients not receiving calcium channel blockers, all of whom were scheduled for inpatient surgical procedures with general anesthesia. INTERVENTIONS: In all patients, anesthesia was induced with high-dose opioids plus a sedative-hypnotic, and intubation was facilitated with 1 to 1.5 mg/kg succinylcholine without nondepolarizing neuromuscular blocker pretreatment. MEASUREMENTS AND MAIN RESULTS: Plasma [K+] was measured prior to induction and 1, 3, 5, 8, 11, and 15 minutes after succinylcholine was administered. A modest average peak rise of 0.5 mEq/L in plasma [K+] was observed, but there were no differences between patients who were or were not receiving calcium channel blockers. CONCLUSIONS: Patients receiving chronic calcium channel blocker therapy are at no greater risk of hyperkalemia after succinylcholine than those not taking such medications. PMID- 8204229 TI - Acute effects of sucralfate aspiration: clinical and laboratory observations. AB - STUDY OBJECTIVE: To assess the complications associated with the aspiration of sucralfate. DESIGN: Clinical (case report) and bench observations. SETTING: Inpatient intensive care unit and experimental animal laboratory. SUBJECTS: The case of a critically ill patient who aspirated sucralfate is presented. Fifteen Sprague-Dawley rats served as experimental animals to investigate the acute histologic effects of large-volume aspiration of sucralfate. INTERVENTIONS: The patient underwent emergent intubation to relieve acute upper airway obstruction. All the animals were anesthetized and had tracheostomies performed. The experimental groups had acidic intratracheal injections of 2 ml/kg of a nonparticulate liquid (pH, 2.3; n = 6) or a sucralfate aspirate (1 ml/kg of a 5% sucralfate suspension of pH 3.6, followed by 1 ml/kg 0.1 of normal hydrochloric acid of pH 1.0; n = 4). Four hours after simulated aspiration, the rats were sacrificed and their lungs removed for histologic examination by light microscopy. MEASUREMENTS AND MAIN RESULTS: Differences were noted in histopathologic injury in the experimental groups compared to the control group using a numeric scoring scale. Nonparticulate acidic liquid aspiration caused a significant increase (p < 0.05) in inflammation. Sucralfate caused a significant increase (p < 0.05) in lung hemorrhage. A nonsignificant trend was seen with simulated sucralfate aspiration for edema and inflammation. No long-term sequelae were attributed to the clinical aspiration episode. CONCLUSIONS: Acute complications associated with aspiration of sucralfate have been identified. In the laboratory setting, simulated aspiration of sucralfate led to acute lung injury. PMID- 8204230 TI - Anesthetic-postoperative morphine regimens for cesarean section and postoperative oxygen saturation monitored by a telemetric pulse oximetry network for 24 continuous hours. AB - STUDY OBJECTIVE: To document the effects of compromised respiratory function on oxygen saturation (SpO2) after cesarean section via the telemetric pulse oximetry network (TPON) for 24 continuous hours. DESIGN: Prospective study. SETTING: Postpartum ward of a university hospital. PATIENTS: ASA physical status I or II parturients undergoing cesarean section. INTERVENTIONS: Healthy parturients were assigned to 1 of 3 anesthetic-postoperative morphine regimens as follows: general anesthesia-parenteral morphine as needed (GA/PM; n = 11); epidural anesthesia parenteral morphine as needed (EA/PM; n = 15); epidural anesthesia-epidural morphine 4 to 5 mg (EA/EM; n = 10). MEASUREMENTS AND MAIN RESULTS: For 24 continuous hours after cesarean section, SpO2, heart rate, and plethysmogram every 10 seconds were recorded by the TPON computer. In addition, pain, somnolence, respiratory rate (RR), and side effects were recorded every 30 minutes to 2 hours. SpO2 less than 94% and less than 92% occurred least with GA/PM. The highest mean cumulative time of SpO2 between 95% and 90% occurred with EA/EM. The longest episode of SpO2 less than 92% and the lowest SpO2 for more than 1 minute also occurred with EA/EM. With all 3 regimens, SpO2 decreased to less than 80% for 20 to 30 seconds at a time, but the lowest SpO2 (less than 85%) for more than 1 minute occurred with EA/EM in 1 patient and was associated with somnolence that required treatment. With all 3 regimens, average RR was within normal limits, but mean RR was significantly lower with EA/EM than with GA/PM or EA/PM from the 8th to the 14th postoperative hours. Somnolence did not differ significantly among the 3 regimens. Pain score was significantly lower with EA/EM than with GA/PM or EA/PM for the first 20 hours. CONCLUSIONS: All 3 regimens risked low SpO2, with the EA/EM regimen having the highest risk but the best analgesia. Neither general nor epidural anesthesia combined with postoperative parenteral morphine influenced SpO2 postoperatively. In this study, the TPON provided a feasible method of detecting hypoxemia early on in the general ward setting. PMID- 8204231 TI - Market costs of short-term physician and nurse anesthesia services. AB - STUDY OBJECTIVE: To estimate the market costs of short-term physician and certified registered nurse-anesthesia (CRNA) services. DESIGN: Survey of large locum tenens agencies. SETTING: University hospital. MEASUREMENTS AND MAIN RESULTS: Negotiations were carried out with agencies for best prices for four weeks of routine anesthesia work. The average cost for an anesthesiologist was $133 per hour and a CRNA, $86 per hour. The agencies received approximately 18% of these costs. CONCLUSIONS: Despite competitive pressures, the locum tenens market charges 55% more for physician than CRNA services. The implications for the different charges are discussed. PMID- 8204232 TI - Impaired ventilatory capacity after recovery from Guillain-Barre syndrome. AB - A 48-year-old woman who failed to disclose significant past medical history presented for laparoscopic-assisted vaginal hysterectomy with general anesthesia. After the uneventful induction of anesthesia, her trachea could not be intubated due to an extremely anterior larynx, and she was allowed to awaken. However, she developed upper airway obstruction and displayed marked muscle weakness with inadequate tidal volumes and marginal oxygen saturation. A history of prior Guillain-Barre syndrome was disclosed by the attending gynecologist. The patient's recovery was complicated by the development of postobstructive pulmonary edema and by respiratory insufficiency requiring the use of mask continuous positive airway pressure (CPAP). Despite vigorous diuresis, her respiratory status and muscle weakness did not significantly improve until she received a trial of aminophylline by infusion, after which she was able to be weaned from mask CPAP support. The patient was discharged home and returned 8 weeks later for surgery. She underwent awake fiberoptic intubation, after which general anesthesia was induced and maintained without complication. An aminophylline infusion was used in the perioperative period until the patient was successfully awakened and her trachea extubated. The frequency of residual muscle weakness after apparent full recovery from Guillain-Barre syndrome is discussed, along with the rationale for the use of aminophylline in this patient's clinical management. PMID- 8204233 TI - Uvular necrosis following endotracheal intubation. AB - Uvular necrosis as a potential source of infection is a poorly detected complication that should be considered as part of the differential diagnosis of postoperative sore throat. We report a unique case of uvular necrosis following endotracheal intubation. The patient complained of a severe sore throat and foreign body sensation 48 hours following surgery. PMID- 8204235 TI - Spontaneous orbital hemorrhage during general anesthesia and arthroplasty. AB - A 72-year-old woman who had a history of arthritis and cerebral vascular accident 4 years earlier underwent hand surgery. Because regional anesthesia was not successful, general anesthesia was administered. Shortly before extubation, proptosis developed in her left eye, and she was unable to open it. The condition was due to spontaneous orbital hemorrhage and resolved with conservative treatment. PMID- 8204234 TI - Anesthetic implications of the child with homocystinuria. AB - We present a 7 1/2-year-old girl with type I homocystinuria who required anesthetic care during repair of bilateral ectopia lentis. Homocystinuria is an autosomal recessive disorder and represents the second most common error of amino acid metabolism. Defective function of the enzyme cystathionine synthetase results in elevated serum levels of methionine and homocysteine. Physiologic disturbances include an increased risk of thromboembolic events and hypoglycemia. Perioperative measures to prevent thromboembolic events include diet therapy to lower serum methionine and homocysteine levels, adequate preoperative hydration, maintenance of intraoperative cardiac output, and the use of pneumatic stockings to prevent peripheral stagnation of blood. Hypoglycemia is thought to be due to alterations in insulin release associated with high levels of circulating sulfur containing amino acids such as methionine. Perioperative measures include normalization of serum methionine and administration of exogenous glucose during periods of fasting. PMID- 8204236 TI - False negative transesophageal echocardiography in a patient with severe mitral regurgitation. AB - We present a patient with severe mitral regurgitation, diagnosed by cardiac catheterization and physical examination but not seen on transesophageal echocardiography (TEE) after general anesthesia. Subsequently, transthoracic echocardiography was performed with the regurgitant jet visualized. This case illustrates one of the limitations of TEE secondary to the use of a biplane probe. The availability and routine use of an omniplane probe may prevent this limitation. A complement of physical examination, imaging, and diagnostic tools, as well as thorough understanding of the limitations of each technique, is essential. PMID- 8204237 TI - Pyriform sinus perforation secondary to traumatic intubation in a difficult airway patient. AB - Pyriform sinus perforation is a relatively rare complication of endotracheal intubation in anesthesia. It can occur after traumatic intubation and is potentially lethal. We recently encountered a patient who developed perforation of the left pyriform sinus when intubation was performed emergently by an inexperienced person in a difficult situation outside the operating room. Clinical manifestations and implications of this complication are discussed. PMID- 8204238 TI - Pneumonitis of unclear etiology in the surgical intensive care unit leading to the demise of an elderly, immunocompromised woman. AB - Multiple system organ failure, likely an expression of a dysregulated immune system, is a common cause of death in the surgical intensive care unit (ICU). While investigational modalities of therapy are on the horizon, current treatment primarily consists of supportive care. The case of an elderly woman who was admitted to the surgical ICU after a celiac axis-superior mesenteric artery bypass, is presented. Her course was complicated by Influenza-B pneumonitis, multiple system organ failure, and, ultimately, death. The course, pathophysiology, and therapeutic modalities involved in this syndrome are discussed. Additionally, the natural history of influenza infection is reviewed. PMID- 8204239 TI - Propofol and alfentanil mixture for outpatient surgery. PMID- 8204240 TI - Facilitation of tracheal intubation by cephalad displacement of the larynx- rediscovered. PMID- 8204241 TI - Gastric bleeding complicating esophageal intubation with a Carden's tube. PMID- 8204243 TI - Remember the gum-elastic bougie at extubation: perhaps not so memorable? PMID- 8204242 TI - Remember the gum-elastic bougie at extubation: perhaps not so memorable? PMID- 8204244 TI - Epidural morphine with butorphanol in pediatric patients. AB - STUDY OBJECTIVE: To determine whether the addition of butorphanol to epidural morphine is effective in reducing the frequency of side effects caused by neuraxial opioids. DESIGN: Randomized, double-blind study. SETTING: Large tertiary care pediatric hospital. PATIENTS: 20 children between the ages of 2 and 17 years undergoing spinal, abdominal, or thoracic procedures. INTERVENTIONS: Patients were divided randomly into one of two groups to receive either 80 micrograms/kg of preservative-free epidural morphine (Group 1) or 80 micrograms/kg of preservative-free epidural morphine with 40 micrograms/kg of butorphanol (Group 2). MEASUREMENTS AND MAIN RESULTS: Blood pressure, heart rate, respiratory rate, and the first need for additional opioids were monitored in the two groups. In addition, pruritus, nausea and vomiting, and supplemental oxygen (O2) required to maintain oxygen saturation (SpO2) above 90% were monitored. Children who received butorphanol in addition to epidural morphine were much less likely to develop pruritus or nausea and vomiting or to require supplemental O2 to maintain SpO2 above 90%. CONCLUSION: Butorphanol 40 micrograms/kg added to epidural morphine 80 micrograms/kg is effective in decreasing the occurrence of side effects caused by neuraxial opioids in pediatric patients. PMID- 8204246 TI - [Primary antiphospholipid syndrome and cerebrovascular disease]. AB - Primary antiphospholipid syndrome (PAS) is characterized by the isolated presence of antiphospholipid antibodies in the absence of other immunological changes. Its association with ischemic cerebrovascular disease is rarely reported. This study analyzes this association in 10 patients (8 women) first presenting with ischemic cerebrovascular accident (ICVA) that met the criteria for PAS. The average age of the patients was 50.4 years. Two patients had Sneddon's syndrome. Prolonged thromboplastin partial activation time was found in only three patients. Eight started aspirin therapy. The average time of follow-up was 17.2 months, during which there was one relapse. PAS should be included as a possible cause when examining individuals with ICVA, particularly when patients are young, when abortion has occurred or when no other cause is evident. Acetylsalicylic acid is effective for preventing relapse when other vascular risk factors are carefully controlled. PMID- 8204245 TI - Effect of nicardipine and diltiazem on internal carotid artery blood flow velocity and local cerebral blood flow during cerebral aneurysm surgery for subarachnoid hemorrhage. AB - STUDY OBJECTIVE: To determine the hemodynamic effects of a bolus injection of nicardipine 1 mg or diltiazem 5 mg on local cerebral blood flow (LCBF) and internal carotid blood flow velocity (ICBFV) with isoflurane anesthesia. DESIGN: Randomized study. SETTING: Inpatient neurosurgery and anesthesia clinic at a city hospital. PATIENTS: 26 patients with subarachnoid hemorrhage who were scheduled for cerebral aneurysm clipping. INTERVENTIONS: A bolus injection of either nicardipine or diltiazem was administered to patients whose systolic blood pressure increased to over 150 mmHg after opening of the dura. MEASUREMENTS AND MAIN RESULTS: After the bolus injection, both drugs rapidly decreased arterial blood pressure. Nicardipine increased LCBF [before injection, 42.1 +/- 12.3 ml/100 g/min; after injection, 47 +/- 10.7 ml/100g/min; (p < 0.05 vs control); after recovery, 42.4 +/- 11.1 cm/sec], but diltiazem did not change LCBF. Nicardipine 1 mg moderately increased ICBFV [before injection, 34.2 +/- 9.3 cm/sec; after injection, 40.6 +/- 8.7 cm/sec (p < 0.01 vs. control); after recovery, 34.1 +/- 8.9 cm/sec], but diltiazem did not change ICBFV. In addition, venous partial oxygen pressure and saturation of the internal jugular did not change throughout the study. There was a close correlation between presurgical neurologic status and LCBF (rs = -0.743; p < 0.01) and ICBFV (rs = -0.721; p < 0.01). CONCLUSIONS: Nicardipine increased LCBF and ICBFV, but diltiazem did not change either. These results suggest that both drugs are useful and safe for the treatment of intraoperative hypertension during cerebral aneurysm surgery. PMID- 8204247 TI - [Changes in neuroexcitatory amino acids during and between migraine attacks]. AB - We studied changes in plasma levels of neuroexcitatory amino acids during and between migraine attacks in 16 patients with migraine without aura, 11 with aura and 21 controls. Glutamic acid levels between attacks were 1.027 +/- 0.60 and 0.890 +/- 0.41 mg/dl in migraine patients without and with aura, respectively; during attacks the levels were 0.535 +/- 0.23 and 0.601 +/- 0.20 for the same patients. The concentration of glutamic acid in the control group was 0.980 +/- 0.64 mg/dl. Aspartic acid levels between attacks in patients without and with aura were 0.179 +/- 0.04 and 0.167 +/- 0.03 mg/dl. Concentrations during attacks were 0.129 +/- 0.02 and 0.119 +/- 0.02 mg/dl for the same patients. Plasma levels of aspartic acid for controls were 0.146 +/- 0.03 mg/dl. We found no significant variations in neuroexcitatory amino acids between migraine attacks in patients with an without aura; changes took place only during attacks, possibly related to the mechanisms of the spreading depression process. PMID- 8204248 TI - [Neurophthalmological alterations in multiple sclerosis]. AB - With the aim of defining the neuro-ophthalmological alterations in multiple sclerosis, both with respect to visual and oculomotor aspects, we have studied a sample of 100 clinically definite multiple sclerosis patients, all in the remittent phase of the disease. We compared them with a sample of 100 unrelated healthy controls, matched for age and sex. Visuomotor alterations were found in 99%, purely visual alterations in 38%, purely oculomotor alterations in 3%, and mixed alterations in 58% of the MS patients. Comparisons with controls showed significant statistical differences in all the tests used in the study. The neuro ophthalmological examination in multiple sclerosis permits us to detect subclinical lesions and arrive at a better comprehension of central nervous system involvement in this disease, thereby contributing collaborating to better patient care. PMID- 8204249 TI - [Cerebroretinal microangiopathy]. PMID- 8204250 TI - [Gelastic seizures, precocious puberty and hypothalamic hamartomas. A case report and the contributions of Single Photon Emission Computed Tomography (SPECT)]. AB - We present a patient with gelastic seizures, precocious puberty and a hypothalamic hamartoma. The diagnostic method of choice for hypothalamic hamartoma is new generation MRI. The characteristic MRI images along with lack of growth during the course of disease indicates a diagnosis of hamartoma firmly with no need for pathological studies. Although the physical nature of gelastic seizures in this syndrome is a subject of dispute, SPECT findings point to activity at a distance from nerve routes connecting the hypothalamus to the cortical regions (the temporal region in this case). Prognosis improves if the various components of the syndrome are treated early and when dysgenesis is less extensive. PMID- 8204251 TI - [Subdural hemorrhage of aneurysmal origin]. AB - Although most subdural hematomas are considered to be venous in origin, they may also be of arterial origin. When subdural bleeding is due to the rupture of an intracranial aneurysm, most commonly at the middle cerebral or internal carotid arteries, the amount of subdural blood is usually small and of no clinical importance. We describe two patients with subdural hematomas secondary to rupture of an intracranial aneurysm, who needed prompt surgical treatment. The first patient had a left internal carotid artery aneurysm at the origin of the ophthalmic artery. In the second patient the aneurysm was at the anterior communicating artery and rebled into the subdural space directly through a right intraparenchymatous frontobasal hematoma. The most probable mechanism of subdural bleeding in our two patients was the existence of adhesions between the aneurysm and the arachnoid due to previous minor hemorrhages. The indication of cerebral angiography in a patient with subdural hematoma is based mainly upon the existence of meningeal signs, the presence of blood in more than one intracranial compartment or the rapid progression of bleeding. PMID- 8204252 TI - [Optic atrophy, sensorineural deafness and sensory neuropathy]. AB - We present a patient with slowly progressing optic atrophy, sensorineural deafness and sensory neuropathy. Clinical examination and testing revealed the exclusively sensorineural nature of this syndrome. Nerve biopsy pointed to primary degeneration. Our review of the literature indicates that this syndrome is categorized as heredo-degenerative. PMID- 8204253 TI - [Meningoencephalitis due to Rickettsia conorii. Etiopathological, clinical and diagnostic aspects]. AB - Boutonneuse fever (BF) is usually considered to be a benign rickettsiosis. However, severe presentations, resembling Rocky Mountain spotted fever, have been reported. There are few neurological complications, except in serious forms of the disease. We present a case of meningoencephalitis in a male adult suffering from BF, and we review the clinical, etiopathogenic and diagnostic aspects among the cases previously reported. We conclude that BF encephalitis would have the following characteristics: a) they mostly affect elderly males; b) they cause altered consciousness level, headaches and low rate of meningeal signs; c) absence of "tache noir"; d) cerebrospinal fluid with slight pleocytosis and/or increased level of proteins, and normal glucose values; e) computerized tomography without significative changes, and f) high rate of morbidity and mortality. We emphasize that we should consider BF in the differential diagnosis of our environmental encephalitis. PMID- 8204254 TI - [Response to combined therapy with plasmapheresis and high doses of immunoglobulin in Lambert-Eaton syndrome]. PMID- 8204255 TI - [Choriocarcinoma presenting as cerebral infarction due to tumor embolism]. PMID- 8204256 TI - Cell transplantation: a future therapy for Parkinson's disease? PMID- 8204257 TI - [Spontaneous conversion of an infarct in a hematoma]. PMID- 8204258 TI - [Treatment of status epilepticus with midazolam: report of four cases]. AB - Midazolam is a water-soluble benzodiazepine imide that has been used in recent years to manage status epilepticus (SE). We describe four patients with SE refractory to conventional treatment, whose seizures were controlled with midazolam administered intramuscularly in two cases and intravenously in the remaining two. Given the pharmacokinetic traits of this drug, the intramuscular route offers great advantages. Midazolam also produces fewer side effects than do other benzodiazepines, suggesting the possibility of its use as a first line treatment for SE and frequent epileptic seizures. PMID- 8204259 TI - [Brain stem encephalitis due to herpes simplex]. AB - Brainstem encephalitis is an unusual infection caused by a variety of agents, among them the herpes simplex (HS) virus. The difficulty of establishing a diagnosis by neurophysiological and radiological examination is greater in this type of encephalitis than in the usual form produced by HS. We describe a fatal case of brainstem encephalitis. Inflammatory and necrotic lesions in the pous and medulla confirmed the clinical diagnosis, while the etiology was determined by immuno-histo-chemical techniques and viral culture of the cerebral parenchyma. Early diagnosis of this form of encephalitis, based on new virological techniques, allows more effective antiviral treatment. PMID- 8204260 TI - [Corticobasal ganglionic degeneration: a report of 7 clinically diagnosed cases]. AB - We report the clinical characteristics of 7 patients (5 women) from 61 through 84 years of age who were diagnosed within the last 3 years as having corticobasal ganglionic degeneration. The disease begin clinically in all patients with on asymmetric motor syndrome. Four experienced tremulousness and myoclonus in one hand, with apraxia and cortical sensory symptoms, astereognosia and sensory extinction. In 3 others, the progressive motor symptoms was mainly a pyramidal syndrome. Hand apraxia caused severe disability in the affected member and was disproportionate to the degree of motor symptoms suffered by the patient. In 3 patients with right side involvement, language-related difficulties were present; in 2 patients with aphasia, difficulties of articulation were partly caused by bucorespiratory apraxia. We believe that this disease, which is more common than believed, has a highly characteristic clinical profile that often allows its clinical diagnosis. PMID- 8204261 TI - [Benign amaurosis fugax]. PMID- 8204262 TI - [Meningioma of the fourth ventricle. Migraine without aura as the first sign]. PMID- 8204263 TI - [Electroencephalographic alterations in patients with migraine with and without aura]. AB - We studied 14 patients with migraine with aura (group 1) and 16 patients with migraine without aura (group 2), 92.8% had EEG alterations in ictal and 57% in the interictal phase in group 1. 37.5% had EEG alterations in ictal and 18.7% in the interictal phase in group 2. There was a statistical difference between the two groups and between both phases. We think that patients with EEG alterations during both phase, may have a lower ischemic threshold. PMID- 8204264 TI - [Peripheral neuropathy and mixed cryoglobulinemia: clinical, neuro- physiological and pathological signs in a group of 12 patients]. AB - This retrospective study involved a series of 12 patients with peripheral neuropathy and mixed type III cryoglobulinemia. The predominating symptoms were sensory. In patients with essential cryoglobulinemia, neuropathy most often presented as multiple mononeuropathy, while polyneuropathic forms were most common among those with secondary cryoglobulinemia. The absence of cryosensitivity was evident in secondary forms. Both neurophysiological and morphological examination revealed a predominance of axonal neuropathy. Two cases of demyelinating neuropathy were found among those with secondary cryoglobulinemia associated with monoclonal gammopathy. Although the vascular lesion was clearly demonstrable in muscle and skin tissue, this was not so in the nervous system. PMID- 8204265 TI - [Electroneurographic parameters in cubital neuropathy of the elbow]. AB - Using conventional techniques with cutaneous electrodes, 14 parameters of antidromic, motor and mixed segmentary sensory conduction of the cubital nerve were assessed in the first 45 patients presenting to us with some form of electroneurographic abnormality. Changes suggestive of axonal degeneration due to a decrease in amplitude or conduction velocity of the distal segment were found in 17. The remaining 28 patients showed only signs of change in conduction velocity at the elbow and could be classified according to electroneurographic degrees of progressive abnormality. Changes in antidromic sensory conduction are early and constant, constituting the parameter of choice for detection of slight compressive neuropathy. PMID- 8204266 TI - [Proposal of a new scale for assessing fatigue in patients with multiple sclerosis]. AB - Fatigue is a complaint often made by multiple sclerosis patients. Description of the symptom varies from patient to patient. This paper proposes a descriptive and quantitative scale for assessing fatigue in these patients. Eighty patients classified as having Poser's type I multiple sclerosis were asked to respond to a questionnaire on the characteristics and variations in fatigue (character, intensity, frequency, periodicity, consequences, mitigating and aggravating factors). Based on the questionnaire, a scale was designed to assess the symptom's spontaneity, nature, severity, frequency of occurrence and existence of Uhthoff's phenomenon. A formula is given for arriving at a global score in the range of 0-17. The scale was then validated by asking two different examiners to apply it prospectively to 32 patients and then calculating the correlation with another quantitative scale of fatigue (Krupp's FSS). The proposed scale had a significant reproducibility (kappa > 0.53) as well as evident correlation with the other scale applied (p < 0.01). The proposed scale is a clear improvement toward a standardized description of fatigue. It is easy to apply, validated and offers advantages over exclusively quantitative scales. PMID- 8204267 TI - Behavioral intervention for cancer treatment side effects. AB - This discussion reviews the current status of behavioral intervention with adult and pediatric cancer patients. It begins by describing the recent entry of behavioral research and practice into comprehensive cancer treatment. The discussion then examines the use of behavioral procedures to control aversive side effects of treatment. Although the control of chemotherapy side effects is the primary focus (most of the behavioral research on symptom control has dealt with reduction of nausea and vomiting with chemotherapy), the application of behavioral principles to other side effects (i.e., anxiety and pain) associated with the aggressive treatment of cancer is assessed. The third topic is behavioral intervention to control child distress during invasive procedures. The discussion ends with a consideration of new directions of research and practice. PMID- 8204268 TI - Anxiety and cancer-related worry of cancer patients at routine follow-up visits. AB - Anxiety and cancer-related worry were assessed in 197 consecutive cancer patients attending follow-up visits. Participants completed questionnaires on three occasions: at the visit, some days later, and three weeks later. Results show that while a majority of patients feel no or only mild anxiety in conjunction to the follow-up visit, about one-fifth report moderate or strong anxiety. Many patients (46%) worry about suffering a recurrence and about overlooking symptoms of new cancer (33%). Patients who were not in complete remission reported higher levels of cancer-related worry concerning the follow-up visit than did patients in remission. Among patients in remission, those who recently terminated treatment reported more overall distress than patients two or more years since treatment termination. PMID- 8204269 TI - On radiation damage to normal tissues and its treatment. II. Anti-inflammatory drugs. AB - In addition to transiently inhibiting cell cycle progression and sterilizing those cells capable of proliferation, irradiation disturbs the homeostasis effected by endogenous mediators of intercellular communication (humoral component of tissue response to radiation). Changes in the mediator levels may modulate radiation effects either by assisting a return to normality (e.g., through a rise in H-type cell lineage-specific growth factors) or by aggravating the damage. The latter mode is illustrated with reports on changes in eicosanoid levels after irradiation and on results of empirical treatment of radiation injuries with anti-inflammatory drugs. Prodromal, acute and chronic effects of radiation are accompanied by excessive production of eicosanoids (prostaglandins, prostacyclin, thromboxanes and leukotrienes). These endogenous mediators of inflammatory reactions may be responsible for the vasodilatation, vasoconstriction, increased microvascular permeability, thrombosis and chemotaxis observed after radiation exposure. Glucocorticoids inhibit eicosanoid synthesis primarily by interfering with phospholipase A2 whilst non-steroidal anti inflammatory drugs prevent prostaglandin/thromboxane synthesis by inhibiting cyclooxygenase. When administered after irradiation on empirical grounds, drugs belonging to both groups tend to attenuate a range of prodromal, acute and chronic effects of radiation in man and animals. Taken together, these two sets of observations are highly suggestive of a contribution of humoral factors to the adverse responses of normal tissues and organs to radiation. A full account of radiation damage should therefore consist of complementary descriptions of cellular and humoral events. Further studies on anti-inflammatory drug treatment of radiation damage to normal organs are justified and desirable. PMID- 8204270 TI - Late sequelae in children treated for brain tumors and leukemia. AB - Forty-two survivors treated at an age of 2-16 years for brain tumors or leukemia were, 4-21 years after treatment, subjected to an extensive follow-up investigation, including physical examination and interview; 35 of them also had endocrinological and 33 psychological evaluation. Hormonal deficiencies were found in about two-thirds of patients and were most common in those treated for brain tumors. The great majority had verbal intelligence quotient (VIQ) within normal range. Also, the performance intelligence quotients (PIQ) were normal in most patients. However, the results suggested that the primary intellectual capacity in children treated for cancer was not being fully utilized, their PIQ being on the average higher than their VIQ; this tendency was especially pronounced in the leukemia patients. PMID- 8204271 TI - Does early physical maturity influence breast cancer risk? AB - Earlier onset of menarche and tallness in adult women are mainly confirmed as risk markers for breast cancer. Recent disparate case-control studies have reported abdominal-type obesity and higher circulating levels of insulin, testosterone and insulin-like growth factor 1, to be further risk markers for breast cancer. There is evidence that abdominal-type obesity is recognisable in girls even before puberty, and disparate studies have shown it to be correlated with earlier onset of menarche, insulin resistance leading to hyperinsulinaemia, and an abnormal sex steroid profile. The implications are that earlier onset of puberty in a subset of girls can lead to more prolonged exposure of developing breast tissue to an abnormal sex steroid profile and also to a higher circulating level of insulin. It is postulated that these metabolic/endocrine concomitants of abdominal-type obesity could play a role in promoting mammary carcinogenesis at a young age, particularly if genetic predisposition is present. PMID- 8204272 TI - Pituitary-gonadal dysfunction in male patients with lung cancer. Association with serum inhibin levels. AB - Male lung cancer patients with poor performance status have an endocrinological dysfunction shown by decreased serum levels of total and free testosterone (AFTC). The intention was to investigate whether or not inhibin plays a role in gonadal dysfunction observed in male patients with malignant pulmonary disease. Twenty-seven patients with locally advanced non-small cell lung cancer were included. Sixteen patients were within ECOG index 1-2 (group A) and 11 patients within ECOG index 3-4 (group B). Gonadal function was monitored by serum LH, FSH, testosterone, SHBG and inhibin levels. Patients with poor performance status displayed significantly lower inhibin (1.6 +/- 0.8 U/I) and AFTC (0.23 +/- 0.07 nmol/l) levels when compared to patients within ECOG index 1-2 (inhibin 2.4 +/- 1.1 U/I; AFTC 0.66 +/- 0.36 nmol/l). Serum inhibin tended to correlate inversely to FSH with a 4.4-fold higher FSH/inhibin ratio in group B compared to A. PMID- 8204273 TI - Serum tumor markers for detection of bone metastasis in breast cancer patients. AB - For the diagnosis of bone metastasis in breast cancer patients during systemic treatment serum tumor markers, including carbohydrate antigens 15-3 (CA 15-3) and 19-9 (CA 19-9), cancer antigen 125 (CA 125), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), beta-2 microglobulin (BMG), ferritin, and tissue polypeptide antigen (determined by the M3 monoclonal antibody, TPS) were measured in 22 patients with known bone metastases and in 30 patients without documented metastases. The most useful single marker was CA 15-3. By stepwise discriminant analysis, it was found that 90% of the patients could be diagnosed truly by using the markers CA 15-3, BMG and ferritin. It is concluded that monitoring with combinations of tumor markers at regular intervals increases the diagnostic efficiency. PMID- 8204274 TI - Expression of HLA-class II antigen in gastric carcinomas. Its relationship to histopathological grade, lymphocyte infiltration and five-year survival rate. AB - To investigate whether the expression of HLA-DR antigen in gastric carcinomas is associated with the survival rate, we studied 70 cases of gastric carcinoma using a monoclonal antibody. Forty-seven cases (67%) stained positively, including 31 differentiated carcinomas, and 16 undifferentiated carcinomas. A close correlation was found between expression of HLA-DR antigen and differentiation of the tumor cells. Marked lymphocyte infiltration was seen in the HLA-DR antigen positive cancers. In advanced gastric cancers, the 5-year survival rate of patients with HLA-DR antigen positive cancers was significantly higher (67.5%) than that of patients with HLA-DR antigen negative cancers (40%). The data suggest that the expression of HLA-DR antigen in gastric carcinomas may reflect the degree of tumor cell differentiation, and influence the host immune response and prognosis. PMID- 8204275 TI - Treatment of primary or metastatic pleural effusion with intracavitary cytosine arabinoside and cisplatin. A phase II study. AB - Thirty-three patients with microscopically verified primary or metastatic malignant pleural effusion were studied: 7 had malignant mesothelioma and 26 metastatic pleural disease. The treatment was based on biochemical and clinical studies which show a synergy between cytosine-arabinoside (Ara-C) and cisplatin. These drugs were instilled in the pleural cavity at the dose of 100 mg for Ara-C and 100 mg/m2 for cisplatin. The cavity was drained after 4 h. If it was possible, the treatment was repeated weekly for 3 times and, after a 6-week rest, it could be started again with the same schedule. The overall response rate (complete plus partial remissions) was 74%. Toxicity was mild or moderate. We conclude that the combination of Ara-C and cisplatin is well tolerated and produces a high response rate in the treatment of malignant pleural effusions. PMID- 8204276 TI - Combined systemic chemotherapy and irradiation of muscle-invasive transitional cell carcinoma of the urinary bladder. AB - A phase II study is presented, which encompasses the period June 1987 until July 1993, and includes 53 patients with muscle-invasive bladder cancer T2-4b who, due to age and/or poor health (37 cases) or primarily extensive lesions (18 cases), were considered inoperable and for whom treatment with neoadjuvant chemotherapy (cisplatin/methotrexate/leucovorin rescue) and radical irradiation was planned. The total number of intended chemotherapy courses could be delivered without undue toxicity to 46 patients (83%) and 44 subsequently underwent radiotherapy: this modality was, by and large, well tolerated. The primary transurethral resection and chemotherapy produced an objective response in 62% of the 53 patients and in 75% of the 44 evaluable patients. The combined programme produced an objective response in 83% of the 37 evaluable patients, 71% in the 44 patients who completed the combined programme and in 59% of the total group of 53 patients. The follow-up ranged from 3 to 62 months. Radiotherapy increased the total objective response rate, proving effective in approximately 50% of patients who did not respond to chemotherapy. The results of this study are regarded as promising and pave the way for a phase III trial. PMID- 8204277 TI - Skin protection by sucralfate cream during electron beam therapy. AB - Acute skin reactions, such as erythema and moist desquamation, constitute major problems during radiotherapy of superficially located tumours. There are no drugs available for the skin care. Sucralfate, a widely used anti-ulcer drug, has anti inflammatory properties, and it activates cell proliferation. Based on these data and our previous experience of sucralfate cream on the aging skin we performed a double-blind randomized study to compare the efficacy of sucralfate cream to a base cream in 50 breast cancer patients receiving postoperative electron beam therapy to their chest wall. The acute radiation reaction of the skin was statistically significantly prevented by the sucralfate cream. The recovery of the skin was also significantly faster in the sucralfate cream group. Side effects due to the cream were rare. PMID- 8204278 TI - Translocation (3;21) in Philadelphia-positive CML blast crisis in a boy with severe skeletal changes. PMID- 8204279 TI - The prevention and treatment of left ventricular thrombosis. PMID- 8204280 TI - [Permanent pacing in childhood: a review of 11 years of experience]. AB - STUDY OBJECTIVE: To review our eleven year experience in the implantation and follow-up of permanent Pacemakers in the paediatric age group. DESIGN: Retrospective study. SETTING: Children submitted to permanent cardiac Pacing implantation and accompanied in the Pacing Center of the Hospital de Santa Maria. PATIENTS: Children from both sexes, aged from neonate to 14 years old, with brady dysrhythmia and indication for permanent cardiac Pacing implantation. MATERIAL AND METHODS: From November 1980 to September 1991, 16 children had permanent Pacemaker implantation. We describe the clinical and electrocardiographic characteristics of the population, mode of Pacing used, technical data from the implantation and evolution. RESULTS: One children died due to associated cardiac defect not related to the Pacemaker. The other 15 children remain in follow-up with normofunctioning Pacemakers and free of symptoms. We had to perform 11 reinterventions in 8 children due to generator or electrode problems (28,2 months reintervention interval). CONCLUSIONS: Improvements in Pacemaker technology and a careful technique of implantation can significantly reduce the morbidity associated to permanent pacemaker implantation in this age group. PMID- 8204281 TI - [Homocysteinemia as a risk factor for early myocardial infarct--a case-control study]. AB - PURPOSE: To investigate if hyper-homocysteinemia represents an independent risk factor of early coronary disease. METHODS: We studied a group of patients under 45 years old, that suffered a myocardial infarction from 3 months and 1 year before the study. The patients were matched with a group of normal controls of a check-up program, in terms of age, sex, smoking habits, presence of hypertension, obesity, (Quetelet Index), presence of diabetes, basal glycemia, total cholesterol, LDL and HDL cholesterol. Later we measured to patients (Pts) and controls (Cts) the plasmatic basal homocysteinemia (B HC) and 6 hours after a methionine overload of 0.1 g/kg body weight (L HC). RESULTS: [table: see text] CONCLUSIONS: In this study hyper-homocysteinemia appears as an independent risk factor of early coronary disease. The measurement of homocysteinemia after the methionine loading test was more discriminative than the basal measurement. PMID- 8204282 TI - [The evaluation of the hemodynamic effects of captopril one year after a myocardial infarct]. AB - In the present study, the authors evaluate the haemodynamic effects of continuous captopril therapy during one-year after a first anterior myocardial infarction (MI). Haemodynamic measurements are made during the first 48 hours after de MI and repeated one year later. Patients are divided in two groups: The first group had therapy with acetylsalicylic acid (ASA) and isosorbide dinitrate (ISDNI) and the second group had therapy with ASA, ISDNI and captopril. From their results the authors conclude that captopril helps peripheral resistances elevations, and that this is one of the mechanisms by which it can have a favourable effect after an anterior MI. PMID- 8204283 TI - [Syncope: how to deal with it?]. AB - Syncope is a frequent symptom, with an expensive protocol of difficult evaluation in face of its diverse causes. The authors describe the proper use of the tests available, particularly the tilt test, and conclude that nowadays only few syncopal episodes would remain unexplained. PMID- 8204284 TI - [A left intraventricular thrombus in an adolescent. Its relationship to the anticardiolipin antibody syndrome]. AB - The authors are going to present the clinical case of a 14-years-old female patient who has got an anticardiolipin antibodies syndrome, a theme to which they add some ideas concerning physiopathology and diagnosis criteria. They'd like to emphasise the echocardiographic observation, which allowed them to find out and follow the evolution of a left sided intraventricular thrombus, the real cause for the systemic thrombosis. PMID- 8204285 TI - [The role of coronary angioplasty in the treatment of ischemic cardiopathy. 1 of 2 parts]. AB - Since its introduction in 1977, coronary angioplasty has gained wide acceptance and is now the primary treatment of coronary artery disease in properly selected patients. In this article the authors review the technique, current indications, contraindications, results and complications of coronary angioplasty. PMID- 8204286 TI - [Dr. Thomaz de Carvalho. The re-evocation of past glories]. PMID- 8204287 TI - [Classification and data collection of the results of paranasal sinus surgery]. AB - In recent years, many techniques for endonasal microsurgery and endoscopic sinus surgery have been developed. This has led to problems in using pathologic findings and reporting results obtained with these procedures. In this article we propose a classification system to eliminate the problems of correlation, standardization and interpretation of the results of paranasal procedures. PMID- 8204288 TI - [The study of evoked otoacoustic emissions in children]. AB - We evaluated the auditory system of 41 children by means of evoked otoacoustic emission. The children were selected from a school population and range in age from 3 to 16 years. No hearing problems were detected prior to this study. The stimulus was a nonlinear click with a frequency of 21/s. All the children but one had echo sizes over 9.72 dB SPL. The mean echo size was 13.23 dB SPL with a reproducibility of 74.81%. Average echo sizes for each frequency are presented. There were no significant differences in the series with respect to the adult comparative pattern used except for the child with an unknown perceptive disorder. We conclude that the test is reliable and highly sensitive, and that it detects small conductive and sensory hearing losses. It is fast, easy, painless and does not require sedation, making it particularly interesting for hearing assessments in childhood. PMID- 8204289 TI - [The histological study of the cochlea of the human temporal bone with the diagnosis of fetal distress]. AB - Hypoacusia is a common audiologic sequela of hypoxia associated with fetal suffering. Nonetheless, the structural features of the cochlear lesions associated with the disorder have not been studied much. We analyzed histopathologically the cochleas of 21 newborns diagnosed as fetal suffering. Each cochlea was dissected from the temporal bone, decalcified in EDTA, included in methacrylate, sliced into serial 10 microns-thick sections, and stained with hematoxylin and eosin. The cochleas of eight newborns were eliminated because of intense autolysis. Of the 13 newborns whose cochlea were considered suitable for histopathologic study, seven had hemorrhage of the vestibular ramp and one had a ruptured Reissner's membrane. The other cochlea was were within the limits of normality. The histologic technique is discussed and the critical factor judged to be the post mortem period prior to sample fixation. PMID- 8204290 TI - [Amoxycillin-clavulanic acid and cefuroxime axetil in the treatment of acute sinusitis. A clinical, radiological and bacteriological evaluation]. AB - Cefuroxime axetil (CAE), an orally absorbed product of cefuroxime, and amoxycillin/clavulanate (AAC), were evaluated for their efficacy and safety in the treatment of acute sinusitis. A total of 47 patients were enrolled in a randomized study to compare cefuroxime axetil 500 mg. b.d. for 8 days (25 patients) with amoxycillin/clavulanate 500 mg. t.d.s for 8 days (22 patients). All patients were evaluable for clinical, radiological and bacteriological response. Of 25 clinically assessable patients treated with CAE, 24 were cured, 1 improved and 1 relapsed (96% success rate). Of 22 assessable patients given AAC, 14 were cured and 8 improved (100% success rate). Two out of 25 (8%) patients treated with CAE experienced drug-related adverse events, including 4% with diarrhoea. In the AAC group, 3 out of 22 (13%) patients had a drug-related adverse event, including 13% with diarrhoea. In conclusion, CAE appears to be as safe and effective as AAC in the treatment of acute sinusitis. PMID- 8204291 TI - [Phonetograms in laryngeal lesions due to vocal abuse]. AB - Using this test, we measure maximum and minimum vocal capacity (sound pressure in dB) from the lowest to the highest frequency that a person can emit and sustain. These measurements are represented on an easily interpreted graph that allows the magnitude of the vocal area to be evaluated. We made phonetograms of persons with nodules (3), polyps (16) and Reinke edema (10) and compared their results to those of a group of 25 healthy subjects. The vocal fields of patients with laryngeal polyp and Reinke's edema were severely reduced. PMID- 8204292 TI - [Laryngeal cancer in Murcia]. AB - A retrospective study was made of a sample of 428 patients with laryngectomy for cancer of the larynx. We analyzed host-dependent factors, personal and familial antecedents, duration of evolution, symptoms, neoplasm site and TNM. Mean age was 60 years. Ninety-eight per cent of the patients were smokers and 60% were moderate or heavy drinkers. The most common location was the supraglottic region (67%) and 8.5% of patients were stage I, 35% stage II, 42% stage III and 15% stage IV. PMID- 8204294 TI - [A implant-supported auricular prosthesis]. AB - A case lf auricular reconstruction of a traumatically missing right ear in a 31 years-old woman is reported. Surgical and prosthetic procedures are described. This experience indicates that it is possible to retain an auricular prosthesis with osseointegrated implants and maintain a reaction-free skin penetration. PMID- 8204293 TI - [ENT emergencies in local hospitals]. AB - We present a descriptive study of ENT emergencies seen at our hospital in 1991 and 1992. The nature of the emergency and its gravity are examined, as well as parameters such as age, sex, diagnosis and referral by a general practitioner. PMID- 8204295 TI - [Adenocarcinoma of the ceruminous glands: report of three cases]. AB - We report three cases of ceruminoma seen in our department over a 1-year period and review the neoplasms of the ceruminous glands. According to the Welti classification, our three cases were ceruminous adenocarcinomas. Based on existing literature, ceruminous adenocarcinoma is the least frequent neoplasm of the ceruminous glands. PMID- 8204296 TI - [Morphological and functional modifications of the acoustic system in golden hamsters with acoustic generalized epilepsy]. AB - We studied the role of the neuronal circuit consisting of the superior olive cochlear hair cells-auditory nerve complex in the pathophysiology of reflex audiogenic generalized epilepsy in the epileptic golden hamster. A direct role of the auditory function can be assumed from the genetic lesions found in these animals' acoustic system. These animals are a model of the anatomopathologic substrate of a type of hereditary neurosensorial hypoacusia. PMID- 8204297 TI - [Benign nasal melanosis transformed into malignant mucosal melanoma: a documented case]. AB - We report a case of nasal mucosal melanosis transformed into malignant mucosal melanoma. We review the feature of these disorders, their association, and preventive treatment. PMID- 8204298 TI - [Diagnostic and therapeutic problems in mucocele]. AB - As mucoceles are manifested usually during the exteriorization phase by compression of surrouding structures, the patient often consults other specialists before seeing an ear nose and throat specialist. We report the case of a female patient first seen in the neurology and ophthalmology departments. The diagnostic procedures and treatment protocols are analyzed. Endoscopic surgery is a good option that requires adequate patient selection. PMID- 8204299 TI - [Laryngeal cancer in females in Camaguey (Cuba)]. AB - We studied cancer of the larynx in women seen at our hospital from 1985 to 1992. The incidence was 15.4%, a figure exceeding that usually reported in the bibliography. It was predominant between 51 and 70 years. The tumors had diverse clinical stages, stage I being predominant with the exception of glottic supraglottic tumors. The most frequent treatment was radiotherapy, followed by total laryngectomy. PMID- 8204300 TI - [Foreign bodies in laryngopharyngeal-esophageal areas]. AB - A case of laryngopharyngoesophageal foreing body is presented. The management, general diagnosis and therapy of these disorders are commented. PMID- 8204301 TI - [Endonasal dermoplasty]. PMID- 8204302 TI - Generation of high-density DNA markers from yeast artificial chromosome DNA by single unique primer-polymerase chain reaction. AB - We have developed a method for the whole sequence amplification of yeast artificial chromosome (YAC) DNA excised from preparative pulsed-field gel electrophoresis using single unique primer-polymerase chain reaction procedures. We used seven contiguous YAC clones, which span 2 Mbp of the Huntington disease gene region on 4p16.3, to amplify the YAC DNAs. The average size of the amplified DNA was approximately 300 bp long, and 12 DNA markers located on the YAC clones positively hybridized with these amplified products, implying that the sequences of the YAC clones were comprehensively amplified by our procedures. These amplified YAC DNAs greatly facilitate the characterization of YAC clones, leading to the detailed analysis of the defined chromosomal region. PMID- 8204303 TI - Yeast artificial chromosome fragmentation vectors that utilize URA3 selection. AB - Two fragmentation vectors, pSE1 and pSE2, were developed for targeting yeast artificial chromosomes (YACs) containing human genomic DNA. Ura- yeast cells containing YACs were selected with 5-fluoro-orotic acid. Fragmented YACs were subsequently generated by transformation to a Ura+ phenotype. Over 80% of the transformants contained YACs of reduced molecular size. These fragmented YACs will prove to be useful in mapping the region of human chromosomes covered by the parental YAC. Fragmentation utilizing URA3 transformation provides a method for producing YAC deletion sets from YACs contained in AB1380 and other ura3- yeast stains. Linkage of a neomycin resistance gene to the URA3 gene facilitates functional analysis of these YACs in eukaryotic cells. PMID- 8204304 TI - A simple and fast method for cloning and analyzing polymerase chain reaction products. AB - A method describing a fast and efficient way for cloning polymerase chain reaction (PCR) products is presented that involves end repair and purification of the PCR product, followed by kinasing and ligation to the vector with the use of a temperature gradient. Efficiency of ligation was estimated to be 50%-70%. Following transformation, cells are plated on MacConkey agar. Bacteria from selected colonies are used directly from the plates for screening without any subsequent purification. Using this protocol, PCR products can be efficiently cloned quickly and economically. PMID- 8204305 TI - A sensitive and quantitative method for the determination of number of HPV 16 DNA copies by using the competitive polymerase chain reaction. AB - The infectivity of human papillomavirus (HPV) is closely linked to the characteristics of the epithelial lesions that it induces in the uterine cervix. In a previous study of ours, we reported that the incidence of positivity for HPV DNA increases as lesions progress toward cervical carcinoma. However, the incidence of positivity did not increase during the process of tumorigenesis from severe dysplasia to invasive carcinoma. These findings suggest that patients with invasive carcinoma had much fewer DNA copies of HPV in host cells. Based on these findings, we have prepared a HPV16 DNA standard (DNA standard) with an EcoRI restriction site by using a polymerase chain reaction (PCR) technique and site directed mutagenesis. We have also developed a sensitive quantitative method based on PCR that uses primers and competition between the patient's HPV16 DNA and an internal DNA standard for the determination of numbers of copies of HPV16 DNA. In this study, uterine cervical tissues obtained from 12 patients with invasive carcinoma were studied using competitive PCR (CPCR) to determine the number of HPV16 DNA copies. We found that the number of copies in the tissues of patients with invasive varied between 5 x 10(6) to 4 x 10(9)/micrograms DNA. PMID- 8204306 TI - A critical review of the optimum duration of chronic rodent testing for the determination of non-tumourigenic toxic potential: a report by the BTS Working Party on Duration of Toxicity Testing. AB - This review indicates that for the detection of non-neoplastic toxic effects: 1. Four decades of accumulated literature provide no lead as to the optimum duration of repeat dose toxicity testing required for all classes of chemicals, although 6 months repeated administration appears adequate for pharmaceuticals. 2. Three month studies predicted the 2 year outcome for 70% of the compounds evaluated in this pilot study using data published by the US National Toxicology Program. 3. In spite of the limitations of this pilot study, this finding is considered encouraging as it is close to that generated previously on more detailed confidential pharmaceutical data. This suggests that the exercise should now be expanded using confidential surveys of industrial data to determine the concordance resulting from the evaluation of a larger group of chemicals. PMID- 8204307 TI - Dextran sulphates protect porcine arterial endothelial cells from free radical injury. AB - 1. The ability of dextran sulphate to protect cultured porcine arterial endothelial cells injured by addition of xanthine and xanthine oxidase (X/XO) or hydrogen peroxide to cell medium was examined using a variety of drug preparations. Cell damage was assessed by determining cell viability (by trypan blue exclusion) and release of lactate dehydrogenase into the medium. 2. Dextran sulphates of average molecular weight (M(r)) 5000, 8000 (hydrogenated or unhydrogenated) at 0.05, 0.5, 5 and 50 micrograms ml-1 medium, added 24 h prior to X/XO, protected cells, whereas dextran sulphate M(r) 500,000 was protective only at 0.5 microgram ml-1. 3. None of the dextran sulphates used showed any toxic effect on cells in concentrations up to 500 micrograms ml-1 medium. 4. When the duration of pretreatment with dextran sulphate M(r) 8000 was varied, 6 h was required for a protective effect on cells damaged by X/XO, which was enhanced with durations of 16 and 24 h. 5. Dextran sulphates had a similar protective effect on cells damaged by hydrogen peroxide. 6. This study suggest that dextran sulphates may prevent conditions resulting from free radical injury. PMID- 8204308 TI - Effects of lead poisoning of rats during pregnancy on the reproductive system and fertility of their offspring. AB - 1. The effects of lead poisoning during pregnancy were tested on female Sprague Dawley rats that inhaled 5 mg m-3 lead oxide for 13 days during gestation. At the end of gestation, the respective blood lead levels of dams and fetuses were 71.1 and 83.2 micrograms 100 ml-1, indicating lead poisoning. 2. In the 90 day-old male offspring of the exposed dams, testis weight and histology, and epididymal weight and sperm reserve, were all similar to those of control males. Spermatozoa mobility and morphology were normal. 3. Also similar to control values were the pituitary weight in these male offspring, their plasma FSH, LH and testosterone levels, and the weight of their ventral prostate and seminal vesicles, the targets of the sexual hormones. 4. When male and female offspring of exposed dams were mated, their fertility was normal, with no increase in prenatal death or malformations, and no changes in the size or sex ratio of litters. 5. These results indicate that, under our experimental conditions, lead oxide inhalation by rats during pregnancy did not perturb reproductive function in their male offspring. PMID- 8204309 TI - Dose dependent effects on lymphoid organs following a single dermal application of sulphur mustard in mice. AB - The effects of a single dermal application of sublethal doses [15.5, 7.75 and 3.88 mg kg-1] of bis(2-chloroethyl)sulphide [sulphur mustard, SM] on body weight, organ/body weight ratio, haematology, histology and cellularity of spleen and thymus were studied after 7 days, in Balb/c mice. A progressive fall in body weight was noticed from the fifth day onwards after SM treatment. A dose dependent decrease in the relative weights of spleen, liver and peripheral lymph nodes, and an increase in adrenal weight were also seen. An increase in red blood cell count, packed cell volume and haemoglobin concentration following SM intoxication were also dose dependent. These changes, together with a significant reduction in the cellularity of the spleen and thymus and degenerative histological changes, show that a single sublethal dermal dose of SM can cause considerable dose dependent systemic effects in Balb/c mice. PMID- 8204310 TI - In vivo inhibition of serum dopamine-beta-hydroxylase by CaNa2 EDTA injection. AB - 1. In humans CaNa2EDTA increases urinary excretion of lead as well as that of essential metals such as zinc, ferrum and manganese but not that of copper. 2. We studied the effect of CaNa2EDTA injection on serum dopamine-beta-hydroxylase, a copper-dependent enzyme, in three male lead welders hospitalized for suspected lead poisoning. 3. Injection of CaNa2EDTA (1000 mg i.v.) resulted in rapid reduction of serum dopamine-beta-hydroxylase activity which returned to normal level within 24 hours. 4. Copper sulphate (8 microns) but not ethylmaleimide (10 mM) restored in vitro serum dopamine-beta-hydroxylase activity to pre-dosing values which indicates that CaNa2EDTA inhibits dopamine-beta-hydroxylase by removing copper from the enzyme. 5. An inverse dose effect relationship between injected CaNa2EDTA and residual serum dopamine-beta-hydroxylase activity was observed. 6. In spite of the reported lack of changes in copper serum concentration, CaNa2EDTA significantly affects the activity of a copper-dependent enzyme in the serum. 7. As CaNa2EDTA is currently the drug of choice for the treatment of asymptomatic lead poisoning in children, the effect of CaNa2EDTA on copper-enzymes requires further investigation. PMID- 8204311 TI - Biochemical renal changes in workers exposed to soluble nickel compounds. AB - 1. Biochemical markers of kidney damage were examined in 14 male and 12 female workers highly exposed to soluble nickel compounds in a chemical plant. The results were compared to those obtained in 12 male and 12 female matched controls. 2. The concentration of nickel in urine of male and female workers averaged 5.0 and 10.3 micrograms g-1 creatinine, respectively. The mean duration of exposure in male and female workers was 25 and 15 years. 3. No difference was found in the mean urinary excretion of lactate dehydrogenase, albumin and transferrin in both sexes, total proteins, beta 2-microglobulin (beta 2-m) and retinol-binding protein (RBP) in males and lysozyme in females. Lysozyme and N acetyl-beta-D-glucosaminidase (NAG) were increased in male and total proteins, beta 2-m, NAG and RBP in female exposed workers. Significant correlations between urinary concentrations of nickel on one side and that of beta 2-m in women (r = 0.462, P = 0.022) and men (r = 0.41, P = 0.018) and of NAG in men (r = 0.405, P = 0.019) on the other side were found in exposed subjects. 4. Results indicate adverse effects of soluble nickel compounds on the kidney tubular function. In agreement with literature data it seems that those effects occur only at high exposure levels. PMID- 8204312 TI - Bronchospasm induced by intravenous adenosine. AB - 1. Adenosine is well known to cause bronchoconstriction when inhaled, but to date, there has been only one report following the intravenous route. 2. Adenosine caused bronchoconstriction in two patients (the only two with asthma) out of 26 treated with the drug. In one subject the duration of response was much longer than previously reported following inhalation. 3. We suggest that adenosine may aggravate bronchospasm in some asthmatics and alternative treatments for supraventricular tachycardia should be considered in this group. PMID- 8204313 TI - Fulminant hepatitis following exposure to dichlorohydrin--report of two cases. AB - A 34-year-old man suffered from fulminant hepatitis after cleaning a tank in which there were traces of dichlorohydrin. In spite of daily plasma exchanges, he died 10 days after exposure. A 27-year-old man with much lighter exposure showed only slight liver dysfunction. This is the first report of lethal injury following exposure to dichlorohydrin. PMID- 8204314 TI - Unusual manifestations after malathion poisoning. AB - We report a case of organophosphate poisoning with a commercial preparation of malathion (deliberate ingestion of Malathane Garden Spray: malathion 15% in isopropyl alcohol) in which the initial cholinergic crisis was followed by cardiac, pulmonary, neurological and renal manifestations. They occurred when erythrocyte and plasma cholinesterases were reactivating. A chemical analysis of the pesticide preparation revealed, apart from malathion itself, the presence of isopropylmalathion and O,O,S-trimethylphosphorothioate. Although pure malathion is regarded as one of the safest organophosphate insecticides, this observation underlines the possibility of severe complications after exposure to a preparation which has been stored for a long period of time. PMID- 8204315 TI - Stress and toxicity. PMID- 8204316 TI - Holiday travel and morbidity reported to general practitioners. AB - AIM: This study set out to explore the influence that holiday travel might have on the rate at which new episodes of illness are reported to general practitioners. METHOD: The study was carried out in a semi-rural practice of five doctors in Wiltshire in 1989. Details of patients' holiday travel were determined by postal questionnaire. Sociodemographic and clinical data were obtained from the patients' medical records. RESULTS: The response rate to the questionnaire was 85%. The study subjects were divided into those who had taken their holiday abroad (n = 643), those who had taken their holiday in the United Kingdom (n = 973), and those who had taken no holiday (n = 668) during the study year. Interim assessment of clinical results revealed no changes in morbidity indices in relation to holiday intervals in any of the groups except for an apparent rise in the number of new episodes of illness presented in the month before departure by those about to go abroad. Further analysis showed that this was due to a significant 112% increase in the number of episodes of illness presented by this study group in the week before they left home. CONCLUSION: This study suggests that the present focus on the supposed excess morbidity of patients returning from foreign holidays is misplaced. PMID- 8204317 TI - Consultation competence in general practice: establishing the face validity of prioritized criteria in the Leicester assessment package. AB - AIM: This study set out to test the face validity of prioritized criteria of consultation competence in general practice as contained in the Leicester assessment package. METHOD: A questionnaire was sent to a geographically stratified random sample of 100 members of the United Kingdom Association of Course Organisers to seek their views on the categories, components and weightings contained in the Leicester assessment package and to determine the proportion of respondents who rejected or suggested a new category, component or weighting or reallocated components to other categories or amended weightings. Their views were sought on a six-point scale (strongly approve, approve, tend to approve, tend to disapprove, disapprove and strongly disapprove). RESULTS: There was a 73% response rate. Of the respondents 99% either strongly approved or approved of the overall set of categories of consultation competence. Only two respondents (3%) expressed any disapproval of individual categories. Thirty five of the 39 suggested components of consultation competence were supported by more than 80% of respondents. There was minimal support for excluding any categories or components of consultation competence, for moving any components to different categories or for the inclusion of new categories or components. Eighty eight per cent of respondents were in favour of the need to identify priorities between any agreed categories of consultation competence and 79% expressed approval of the suggested weightings. Although 42% of respondents indicated a wish for some alteration in weightings, the mean values for all consultation categories suggested by all respondents were almost identical to the original weightings in the Leicester package. CONCLUSION: The face validity of the categories and components of consultation competence contained in the Leicester assessment package has been established, and the suggested weightings of consultation categories have been validated. Consequently, the criteria contained in the Leicester package can be adopted with confidence as measures against which performance can be judged in formative or summative assessment of consultation performance in general practice. PMID- 8204318 TI - Detection of Chlamydia trachomatis in general practice urine samples. AB - BACKGROUND: Chlamydia trachomatis is frequently overlooked as a cause of dysuria and urinary frequency in general practice patients. AIM: This study set out to determine the impact of performing chlamydial antigen detection on sterile pyuria samples from patients aged 16-65 years and which were submitted to a hospital microbiology laboratory by general practitioners in the Winchester health district for routine microbiological investigations. METHOD: Chlamydial antigen detection was performed by enzyme immunoassay and direct immunofluorescence. The cost of performing the test was estimated. In the first year of the study (1991) questionnaires were sent to general practitioners whose patients had a positive test result. RESULTS: A total of 1025 samples of sterile pyuria were received at the laboratory between January 1991 and March 1993. Chlamydial antigen was detected in 54 samples (5%); 22 men and 32 women aged between 16 and 57 years (mean 25 years). The detection rate was highest in the 16-20 years age group (22% of men had a positive sample and 7% of women). Completed questionnaires from 27 general practitioners revealed that 59% of their patients were referred to the genitourinary clinic for treatment and contact tracing. The others were treated by the general practitioner. The cost of the screening programme per cure in this population was estimated to be 246 pounds. CONCLUSION: C trachomatis is a significant pathogen which may go unrecognized and untreated. The cost, medically and financially, of screening for this pathogen and treating infected patients and contacts is likely to be less than ignoring it, particularly if screening is confined to the 16-30 years age group. General practitioners should consider the diagnosis of chlamydial infection in young adult patients with sterile pyuria, and microbiology laboratories should screen sterile pyuria samples for chlamydial antigen. PMID- 8204319 TI - Evaluation of the use of general practice age-sex registers in epidemiological research. AB - AIM: This study set out to show how well samples from general practice registers compare with census data, to describe those characteristics of the population and of the register that influence the response to postal surveys, and to demonstrate how general practice records can be used to assess non-response bias. METHOD: The data for this study were obtained from a large postal survey about low back pain among the general adult population aged 20-59 years in eight areas of the United Kingdom, using general practice age-sex registers as the sampling frame. RESULTS: The overall response rate was 59%. In the areas chosen, general practice registers yielded samples of size and age-sex composition close to that predicted from national census data. Responses were more likely to be obtained from women, from older age groups and from practices where the sample lists had been inspected for errors. The use of computerized registers and a letter of recommendation from the general practitioner had no effect on the response rate. Inspection of the general practice records of subsamples of respondents and non respondents to determine consultation rates suggested that there was little response bias in respect of the subject of the survey. CONCLUSION: General practice registers can provide a suitable sampling frame for epidemiological purposes. Inaccuracies in the register can be reduced to some extent by careful inspection, but an irreducible minimum remain. Information held in general practice records can be useful in assessing response bias in health surveys. PMID- 8204320 TI - Knowledge of and reported asthma management among South Australian general practitioners. AB - AIM: This study, carried out in 1989, set out to assess general practitioners' knowledge of asthma management and their reported management practices. METHOD: Of 153 randomly selected South Australian general practitioners 127 (83%) completed a questionnaire designed to explore issues relating to the management of asthma. RESULTS: The survey revealed substantial differences between general practitioners in their knowledge and management practices including the assessment of the severity of asthma, the need for objective monitoring, that is by the use of spirometry and peak flow meters, and the use of medication. Overall, the sampled general practitioners believed that patient-related factors were the main barriers to effective treatment of asthma. CONCLUSION: The findings of this study suggest that ideal asthma management was not being attained. More research is required to ascertain why such variability among practitioners exists and how best to remedy these differences. PMID- 8204321 TI - Screening for childhood asthma using an exercise test. AB - BACKGROUND: Screening for asthma in children in the community could have advantages at a time when prevalence rates of the condition and associated hospital admission rates are rising. AIM: The aim of this study was to assess the usefulness of a standard exercise test as a marker of asthma or potential asthma in children, and to examine the relationship between asthma and other respiratory tract illnesses. METHOD: In 1985 a cross-sectional research study was undertaken in 10 primary schools in West Glamorgan; the children were followed up over six years until 1991. The exercise test involved measuring peak expiratory flow rate before and after the children ran as fast as they could for six minutes. A control group of children with a negative exercise test result were compared with those not known to have asthma who had a positive result (fall in peak expiratory flow rate of 15% or greater), using clinical data. Similar clinical comparisons were undertaken between the children known to have asthma and a control group. RESULTS: Of 864 children not known to have asthma, 60 had a positive exercise result. Of 92 children known to have asthma, 33 had a positive test result and seven were unable to finish the test because of bronchospasm, a sensitivity of 43% and a specificity of 93%. Follow up of 55 of the 60 children not known to have asthma but who had an abnormal response to the test showed that 32 had developed clinically recognizable asthma six years later. There was a significantly higher prevalence of atopic and respiratory illnesses (otitis media, hay fever and eczema) in the group of children with bronchial hyperreactivity demonstrated on exercise than in those without bronchial hyperreactivity. CONCLUSION: This research shows that bronchial hyperreactivity demonstrated by an exercise test can be a marker for childhood asthma. The study has also identified other respiratory tract illnesses which appear to belong to the same spectrum as asthma. PMID- 8204322 TI - Should general practitioners be testing for depression? AB - While most patients with recognized depressive illness are treated by general practitioners without referral, there is evidence that many patients classifiable as depressed after psychiatric interview are not diagnosed as such. Missing depression is of great importance since it is now eminently treatable. This paper explores the use in primary care of questionnaire tests for depression and also their role in case finding in vulnerable groups of patients. The potential of existing validated questionnaires in clinical work and audit is largely unexploited. As yet, however, there is no gold standard for the diagnosis of depression seen in primary care. Clusters of symptoms do not yet accurately predict the course of the illness or response to treatment. More research is needed on the natural history of depression seen in the community, as well as on treatment and outcome. PMID- 8204324 TI - Counselling. PMID- 8204323 TI - Active euthanasia--time for a decision. AB - There has been renewed interest in the moral arguments surrounding euthanasia. Some patients are now apprehensive of advanced medical technology which they fear may result in a prolonged and undignified death. In the current situation of scarce resources for health care, both patients and doctors could be coerced into considering active euthanasia if it was legally available. In this paper it is argued that doctors now need to make a clear statement rejecting active euthanasia but affirming that in certain cases passive euthanasia, or letting die, may be morally justifiable. PMID- 8204325 TI - Prescribing generic drugs. PMID- 8204326 TI - Antenatal care project. PMID- 8204327 TI - 'Mobile' patients. PMID- 8204328 TI - Diabetes care. PMID- 8204329 TI - Counselling in general practice. PMID- 8204330 TI - Practice policies for responding to patients with chest pain. PMID- 8204331 TI - Randomized controlled trial of the effect of the Royal College of Radiologists' guidelines on general practitioners' referrals for radiographic examination. AB - BACKGROUND: The Royal College of Radiologists' guidelines aim to encourage more appropriate use of diagnostic radiology and so reduce the use of clinically unhelpful x-ray examinations. AIM: The object of this study was to conduct a randomized controlled trial of the introduction of the guidelines into general practice. METHOD: A total of 62 practices (170 general practitioners) referring patients to St George's Hospital, London for diagnostic radiology were randomly allocated into two groups. Guidelines were sent to the 30 practices in the intervention group. Radiological referral patterns were compared in both groups before and after the introduction of guidelines. RESULTS: Practices which had received guidelines requested significantly fewer examinations of the spine, and made a significantly higher proportion of requests which conformed to the guidelines compared with practices which had not received the guidelines. There were no significant differences in the proportion of forms giving physical findings or in the proportion of positive findings at radiology. CONCLUSION: Introduction of guidelines can influence general practitioners' radiological referrals in the short term. Wider use of guidelines might help to reduce unnecessary irradiation of patients. PMID- 8204332 TI - Registration health checks: inverse care in the inner city? AB - BACKGROUND: Attendance at health checks of patients already registered with a general practitioner is known to be poor, with those in need least likely to attend. Little is known of the efficacy of such checks for newly registered patients. AIM: This study set out to determine the characteristics of attenders and non-attenders at health checks for patients registering with a general practitioner in east London, and the effect of health checks on motivation to change unhealthy lifestyles. METHOD: A questionnaire analysis was carried out of patients aged 16 years and over at registration and after a health check in seven east London training practices. Questionnaires asked about personal background and lifestyle including smoking status, alcohol intake, diet, weight, exercise, cervical smear uptake, and motivation to change unhealthy aspects of lifestyle. RESULTS: Questionnaires were offered to 356 patients registering with the practices, of whom 101 declined or returned inadequate data. Of the remaining 255 patients, 118 (46%) attended a health check with 113 completing a second questionnaire after the check. Non-attenders were significantly more likely than attenders to be of lower social class, unemployed, of African origin and to be heavy smokers. Women who did not attend were significantly less likely than attenders to have had a cervical smear within the last three years. Non-attending mothers were significantly more likely than attending mothers to be single parents. Motivation among attenders to stop smoking and drink less alcohol was increased significantly after the health check. CONCLUSION: Attendance at registration health checks at these practices was poor and non-attenders tended to be more socially deprived than attenders and had relatively unhealthy lifestyles. Although the health checks increased the attenders' motivation to alter smoking and drinking habits, inviting all new patients to a health check would appear to result in poor targeting of health promotion resources and may widen inequalities in health. PMID- 8204333 TI - Consultations for women's health problems: factors influencing women's choice of sex of general practitioner. AB - AIM: This study set out to examine the degree to which women choose to visit a woman doctor for women's health problems and the determinants of this choice. The differences between women and men doctors with regard to treating women's health problems were also studied. METHOD: Data from the Dutch national survey of general practice were used. All group practices with both women and men general practitioners were selected. Analyses were restricted to consultations among women aged 15-65 years about menstruation, the menopause, vaginal discharge, breast examination and cervical smear tests. RESULts. Given the size of their female practice population, women doctors saw considerably more women with women's health problems than did their male colleagues. Women were more likely to consult a woman general practitioner if she was more available (that is, working longer hours), and younger women were more likely than older women to choose women general practitioners. Sex differences in the treatment of women's health problems were small and mainly related to the verbal part of the consultation: counselling and providing information. The doctors' availability and their certainty about the working diagnosis explained differences in the verbal aspects of consultations. Women general practitioners had longer consultations than their male colleagues mainly because more health problems were presented per consultation. CONCLUSION: In order to increase the possibility of patients choosing women general practitioners, policy should be directed towards the education of more women general practitioners and women general practitioners should be encouraged to work more days a week. PMID- 8204334 TI - Evaluation of a rule base for decision making in general practice. AB - BACKGROUND: Decision making in general practice relies heavily on judgmental expertise. It should be possible to codify this expertise into rules and principles. AIM: A study was undertaken to evaluate the effectiveness, of rules from a rule base designed to improve students' and trainees' management decisions relating to patients seen in general practice. METHOD: The rule base was developed after studying decisions about and management of thousands of patients seen in one general practice over an eight year period. Vignettes were presented to 93 fourth year medical students and 179 general practitioner trainees. They recorded their perception and management of each case before and after being presented with a selection of relevant rules. Participants also commented on their level of agreement with each of the rules provided with the vignettes. A panel of five independent assessors then rated as good, acceptable or poor, the participants' perception and management of each case before and after seeing the rules. RESULTS: Exposure to a few selected rules of thumb improved the problem perception and management decisions of both undergraduates and trainees. The degree of improvement was not related to previous experience or to the stated level of agreement with the proposed rules. The assessors identified difficulties students and trainees experienced in changing their perceptions and management decisions when the rules suggested options they had not considered. CONCLUSION: The rules developed to improve decision making skills in general practice are effective when used with vignettes. The next phase is to transform the rule base into an expert system to train students and doctors to acquire decision making skills. It could also be used to provide decision support when confronted with difficult management decisions in general practice. PMID- 8204335 TI - Patient satisfaction surveys as a market research tool for general practices. AB - BACKGROUND: Recent policy developments, embracing the notions of consumer choice, quality of care, and increased general practitioner control over practice budgets have resulted in a new competitive environment in primary care. General practitioners must now be more aware of how their patients feel about the services they receive, and patient satisfaction surveys can be an effective tool for general practices. AIM: A survey was undertaken to investigate the use of a patient satisfaction survey and whether aspects of patient satisfaction varied according to sociodemographic characteristics such as age, sex, social class, housing tenure and length of time in education. METHOD: A sample of 2173 adults living in Medway District Health Authority were surveyed by postal questionnaire in September 1991 in order to elicit their views on general practice services. RESULTS: Levels of satisfaction varied with age, with younger people being consistently less satisfied with general practice services than older people. Women, those in social classes 1-3N, home owners and those who left school aged 17 years or older were more critical of primary care services than men, those in social classes 3M-5, tenants and those who left school before the age of 17 years. CONCLUSION: Surveys and analyses of this kind, if conducted for a single practice, can form the basis of a marketing strategy aimed at optimizing list size, list composition, and service quality. Satisfaction surveys can be readily incorporated into medical audit and financial management. PMID- 8204336 TI - Attitudes of general practitioners in New Zealand to pharmaceutical representatives. AB - BACKGROUND: Pharmaceutical representatives are a vital component of the marketing of pharmaceutical products and an important source of prescribing information for general practitioners. AIM: A study was undertaken to explore the attitudes of New Zealand general practitioners to pharmaceutical representatives. METHOD: A questionnaire survey of 100 general practitioners was undertaken to which 67 general practitioners responded. RESULTS: The provision of practical prescribing advice by representatives and gifts relevant to medicine were seen as desirable activities by many respondents. However, gifts of value considerably greater than suggested acceptable in recent guidelines for general practitioners were also highly favoured by some practitioners. CONCLUSION: Current ethical guidelines setting out the relationship between pharmaceutical representatives and medical practitioners are inadequate and should be based on the need for the general practitioner to become an unbiased promoter of patient health. PMID- 8204337 TI - Involvement of the primary health care team in coronary heart disease prevention. AB - BACKGROUND: Recent years have seen a vast increase in the amount of health promotion activity undertaken in general practice. AIM: This study set out to identify the level of general practitioner and nurse involvement in activities aimed at coronary heart disease prevention and to examine variations in involvement. METHOD: A questionnaire survey was undertaken of a sample of general practitioners across England and the nurses who worked in their practices. RESULTS: Of 1696 randomly selected general practitioners 64% completed a questionnaire, of 928 practice nurses 71% responded and of 682 health visitors and 679 district nurses 52% and 40% responded, respectively. Of the general practitioners 94% reported that they were involved in assessing lifestyle risk factors in the routine consultation and regular assessments most commonly involved blood pressure testing and inquiry about smoking status. Eighty six per cent of practices were reported by the practice nurse as having well person clinics; these clinics were usually run by the practice nurse. Clinics for the management of specific lifestyle risk factors were also usually run by practice nurses, although many doctors were involved in hypertension clinics and cholesterol clinics. Health visitors and district nurses had a low level of involvement in this practice based clinic activity. Involvement of general practitioners and practice nurses in coronary heart disease prevention was associated with training in health promotion and positive attitudes towards prevention and health promotion. The level of involvement of practice nurses in health promotion was associated with the support received from primary health care facilitators, family health services authorities and district health authorities. CONCLUSION: Members of the primary health care team appeared to have their own distinct area of preventive activity. However, this division did not appear to be a result of organized teamwork and deployment of skills and expertise according to a clearly defined management protocol. Instead it seemed to be a product of general practitioner contract and management arrangements which tended to encourage an approach to general practice health promotion which revolved around the practice nurse and which hindered the development of a broader team based approach to planning and delivery of health promotion in relation to the needs of the practice population. PMID- 8204338 TI - Controlled trials in the evaluation of counselling in general practice. AB - In this paper the difficulties of conducting a controlled evaluation of counselling (brief psychotherapy) in general practice are discussed. Results of a pilot study indicate that patients referred by family doctors to counsellors are often seriously emotionally distressed and recovery is slow. Counsellors come from different backgrounds and use a variety of therapies. Although the results show that controlled research is feasible, in a definitive trial patients should be randomized in a stratified manner, according to severity, by the researcher after initial assessments have been made. Counsellors should have a recognized accreditation and preferably be employed for the trial to ensure uniformity of approach and avoid long waiting lists. Blind assessments of outcome are desirable but are not always feasible and reliance on patient self-report is important. Within the limitations of current knowledge, only controlled evaluations will provide a greater understanding of the efficacy of counselling in general practice. PMID- 8204339 TI - Effecting change in frequent non-attenders. PMID- 8204340 TI - Depression among cancer patients. PMID- 8204341 TI - Abnormal menstrual bleeding in perimenopausal women. PMID- 8204342 TI - Non-attenders for cervical screening. PMID- 8204343 TI - Continuity of care. PMID- 8204344 TI - Sleep loss in elderly people. PMID- 8204345 TI - Oncogenes and radiosensitivity. PMID- 8204346 TI - Phase I and pharmacological study of intra-arterial hepatic administration of pirarubicin in patients with advanced hepatic metastases. AB - Intra-arterial hepatic (i.a.h.) administration of the doxorubicin analogue pirarubicin was evaluated in a phase I trial, based on preclinical studies that showed an advantage of pirarubicin over doxorubicin after locoregional hepatic administration. Pirarubicin was given to 9 patients with metastatic liver disease with intrapatient dose escalation. Of the 58 cycles evaluable for tolerance, no hepatobiliary or vascular toxicity was observed. The dose-limiting toxicity was granulocytopenia: the maximum administered doses ranged from 50 to 120 mg/m2, suggesting variable rates of pirarubicin hepatic extraction between patients. Pharmacokinetic data obtained in 7 patients, in which a direct comparison of intravenous (i.v.) and i.a.h. administration was possible, indicated a median i.v./i.a.h. ratio of 7.4 for the maximal plasma concentration, and a median ratio of 4 for the area under the plasma concentrations versus time curves, suggesting a high pirarubicin hepatic extraction. An unexpectedly high response rate was observed: two complete (colorectal carcinoma) and two partial responses. These data demonstrate that i.a.h. pirarubicin not only produced high locoregional concentrations and reduced systemic exposure, but can also achieve responses in metastatic liver disease of colorectal origin. PMID- 8204347 TI - Inconsistent expression of HLA-B antigens on peripheral blood lymphocytes of stage I melanoma patients: an indicator of poor prognosis. AB - The survival of stage I melanoma patients was evaluated and compared with the detectable expression of HLA antigens. Of 904 patients who were surgically treated, 219 were HLA typed on peripheral blood lymphocytes. Four consecutive HLA typings were considered necessary. Median follow-up was 8 years. Two main groups of patients were considered: (a) patients with consistent detectable expression of antigens; and (b) patients with inconsistent detectable expression of antigens. Patients with consistent HLA antigens detection had an 8-year survival rate of 87.7% compared with 49.2% of patients with an inconsistent rate (P10(-7). Multivariate analysis of survival of the 182 HLA-typed patients who survived at least 24 months from surgery showed that two of the criteria had an independent impact on survival: tumour thickness (P 0.02) and HLA typing (P 2 x 10(-5). Inconsistent detection of HLA antigens on peripheral blood lymphocytes during the first 24 months after surgery is an indicator of poor prognosis in stage I melanoma patients. PMID- 8204348 TI - VP-16, ifosfamide and cisplatin (VIP) for extensive small cell lung cancer. AB - Thirty-seven extensive disease SCLC patients were treated with ifosfamide 1.0 g/m2 (maximum 1.75 g), VP-16 (etoposide) 75 mg/m2 and cisplatin 20 mg/m2 (VIP) daily for 5 days in hospital. Mesna was given as a continuous infusion until 12 h after the last ifosfamide dose. Treatment was reduced to 4 days after the first 8 patients experienced serious myelotoxicity. 30 patients were evaluable for response. 8 (27%) achieved a complete response and 60% had a partial response. The median duration of response was 23 weeks. The median survival of all 37 patients was 41 weeks, and 47 weeks for the 30 evaluable patients. Fifty per cent and 26% of the evaluable treatment courses were associated with grade 4 and 3 granulocytopenia, respectively. There were eight febrile events including four treatment-related deaths from sepsis on the 5-day regimen. Although the response to VIP was generally rapid, the proportion achieving complete response (27% of evaluable patients) and the median survival is similar to standard chemotherapy regimens which are less toxic and less complex to administer. PMID- 8204349 TI - Subsequent primary cancers following bladder cancer. AB - The incidence of a subsequent primary cancer was investigated among 10,014 patients with cancer of the urinary bladder diagnosed in 1953-1989 in Finland. During the follow-up period of 1953-1989, 652 new metachronous cancers were diagnosed. The number equals the expected number based on the national incidence figures. There were 195 second cancers of the lung. The standardised incidence ratio (SIR) for lung cancer was 1.3 among males [95% confidence interval (CI) 1.1 1.4] and 2.6 among females (95% CI 1.4-4.5). An increased SIR for larynx cancer in males (SIR = 1.7, 95% CI 0.91-2.8) and for kidney cancer in females (SIR = 3.6, 95% CI 1.8-6.2) was observed. The risk of a second cancer was greater among patients less than 60 years of age at the time of first diagnosis than among older patients. No consistent differences were observed in the risk of new cancer between bladder cancer patients treated with or without radiotherapy. PMID- 8204350 TI - The prognostic value of insulin-like growth factor-I in breast cancer patients. Results of a follow-up study on 126 patients. AB - The insulin-like growth factor-I is an important mitogen and has a growth promoting property, especially in breast cancer. This work analyses the prognostic value of the insulin-like growth factor receptor-I (IGFR-I), which belongs to the group of membrane receptors for growth factors. The study included 126 patients. 49 patients (39%) were IGFR positive (> or = 4.0%). There was a significant correlation between IGFR and oestrogen receptor (ER) status (P = 0.001), but not between IGFR and progesterone receptor status (PR; P = 0.07). There was no correlation between node status and IGFR. The expression of IGFR had a strong significance in the disease-free analysis (P = 0.0108). The IGFR status was not of predictive value in the node-negative subgroup (64 patients). Within the ER-negative group, the disease-free analysis further stratified with IGFR revealed that patients with IGFR-positive and ER-negative cancers are in a worse situation than IGFR-negative ER-negative cancer patients (P = 0.01). PMID- 8204351 TI - A comparison of early effects with two dose rates in brachytherapy of cervix carcinoma in a prospective randomised trial. AB - This phase III randomised trial examined the early effects of two low dose rates (0.38 and 0.73 Gy/h) in brachytherapy of stage I and IIp cervical cancer patients. A total of 204 patients were included between January 1985 and September 1988. Since the main analysis of this paper concerned surgical difficulties, only the 155 patients (76%) on whom surgery was performed at the Institut Gustave-Roussy were retained in this analysis. Treatment consisted of uterovaginal 137Cs irradiation followed by immediate or deferred surgery. The two groups were similar for pretreatment characteristics except for endocervix involvement. Their brachytherapy parameters were also similar (60 Gy pear dimensions, doses to critical organs, total kerma, etc.). The factors with a poor prognosis were, for surgical difficulties, older age, stage II and a small irradiated pear volume; for difficulties with haemostasis, immediate surgery, stage II and previous surgery; and for difficulties in dissection, lymph node involvement. The dose rate significantly influenced surgical difficulties for the stage IIp patients operated on by deferred surgery. Those treated with the higher dose rate showed a 2-fold increase in surgical difficulties compared to those irradiated at the lower dose rate (P = 0.03). The independent prognostic factors for sterilisation of the surgical specimen were small tumour size and absence of lymph node involvement. An inverse dose rate effect was observed for medium size tumours, with significantly more sterilisations observed in stage IIp patients in the lower dose rate group (P < 0.01). PMID- 8204352 TI - Serum concentrations of cytokines in patients with Hodgkin's disease. AB - Serum concentrations of interleukin (IL)-1 alpha, IL-2, IL-4, IL-6 and tumour necrosis factor (TNF) were measured in 24 untreated patients with Hodgkin's disease and in 24 healthy volunteers matched for age and sex. Serum levels of IL 1 alpha were significantly higher in patients with Hodgkin's disease. The number of patients with detectable serum IL-2 or IL-6 levels was significantly higher in patients with Hodgkin's disease as compared to the control group. No difference was observed for TNF. IL-4 was undetectable in all patients. Serum cytokine levels were not significantly different in patients with and without systemic "B" symptoms (weight loss or fever and night sweats) in the different histological subtypes and clinical stages. Serum concentrations of IL-1 alpha, IL-2, IL-6 and TNF were not correlated to the erythrocyte sedimentation rate, fibrinogenaemia or thrombocyte number. These results indicate that subsets of patients with Hodgkin's disease have detectable serum IL-1 alpha, IL-2 and IL-6 levels, but that other mediators are likely to be involved in the associated clinical and biological inflammatory syndrome. PMID- 8204353 TI - 5-Fluorouracil, folinic acid, etoposide and cisplatin chemotherapy for locally advanced or metastatic carcinoma of the oesophagus. AB - 38 patients with advanced oesophageal carcinoma were treated with intravenous (i.v.) folinic acid (300 mg/m2), 5-fluorouracil (500 mg/m2), etoposide (100 mg/m2), and cisplatin (30 mg/m2) (FLEP), on days 1, 2 and 3, every 22-28 days. 26 patients had locally advanced disease (LAD) and 12 had metastatic disease (M1). Oesophagectomy was planned for patients with LAD in case of tumour regression after chemotherapy, while patients with M1 disease received chemotherapy only. The overall remission rate was 45% (17/38) including four clinical and two pathologically confirmed complete remissions. 16 patients underwent oesophagectomy, 12 after response to FLEP, and 4 after FLEP and subsequent irradiation +/- 5-fluorouracil/mitomycin. Toxicity was mainly haematological, with WHO grade 3 and 4 leukocytopenia in 50% and thrombocytopenia in 31% of the patients. Two treatment-related deaths were observed; one due to chemotherapy and one postoperatively. Median survival time of LAD patients was 13 months, and actuarial 2-year survival was 31%. Patients with complete tumour resection after FLEP had a median survival time of 18 months and a 2-year survival rate of 42%. Median survival of M1 patients was 6 months. FLEP is an active combination for oesophageal cancer, especially when used preoperatively in LAD. PMID- 8204354 TI - The treatment of metastatic renal cell carcinoma by continuous intravenous infusion of recombinant interleukin-2. AB - Between March 1989 and June 1990, 133 patients were treated with interleukin 2 (rIL-2) for metastatic renal cell carcinoma (RCC) in a multicentre open non randomised study. The results show an objective response rate of 14% (95% confidence interval 8-21) with 4 patients achieving a complete remission. This is in keeping with the data from previous studies using rIL-2 by continuous infusion. It is of interest that 87% of objective responses occurred in hospitals that entered 5 or more patients. PMID- 8204355 TI - Survival and prognostic factors in patients with localised cutaneous melanoma observed between 1980 and 1991 at the Istituto Dermopatico dell'Immacolata in Rome, Italy. AB - 530 patients with localised cutaneous melanoma consecutively observed between 1980 and 1991 at a hospital for skin diseases in Rome, Italy, were studied. Crude survival proportions were calculated with the method of Kaplan and Meier. Cox proportional hazards regression analysis was used to estimate the effect of prognostic factors on death rates. Females and younger patients had better 5- and 10-year survival rates, while increasing tumour thickness was associated with a decrease in survival time. In the multivariate analysis, an independent association with survival was found for tumour thickness, presence of ulceration, age, sex and cross-sectional profile of neoplasia. Our study confirms that females and young patients with thin melanomas have a better prognosis, while the importance of cross-sectional profile needs further study. PMID- 8204357 TI - Obesity and cancer risk: a Danish record-linkage study. AB - A cohort of 43,965 obese persons was accrued on the basis of discharge registrations from Danish hospitals, and incidence of cancer in the cohort was compared to that in the Danish population as a whole using indirect standardisation for age and period. Increased incidence was observed for cancer of the uterine corpus independently of age [114 cases, relative risk (RR) = 2.0, confidence interval 1.6-2.4], and for breast cancer in women above the age of 70 (133 cases, RR = 1.2). These findings are consistent with previous studies. In younger women, breast cancer occurred less frequently and ovarian cancer occurred more frequently than expected. Increased incidence was observed for cancers of the oesophagus (26 cases, RR = 1.9) and the liver (58 cases, RR = 1.9), probably reflecting an increased prevalence of excessive alcohol consumption in the cohort. Increased incidence was furthermore observed for cancers of the pancreas (101 cases, RR = 1.7), the prostate (96 cases, RR = 1.3) and the colon (195 cases, RR = 1.2), which may indicate the existence of risk factors which are common to obesity and to these cancers, for example, dietary habits. Kidney cancer was increased in women only. Overall, the incidence of cancer was increased by 16% in the cohort. The results were essentially unchanged by restriction to the subcohort of 8207 persons in whom obesity was the primary discharge diagnosis, and were also similar in the first year of follow-up after hospital discharge. Selection bias is, therefore, not likely to have influenced the results. PMID- 8204356 TI - Phase II trial of 5-fluorouracil and the natural l isomer of folinic acid in the treatment of advanced colorectal carcinoma. AB - Between February 1991 and July 1992, 79 previously untreated patients with metastatic colorectal carcinoma were enrolled in a phase II study of combined 5 fluorouracil (5-FU) and l-folinic acid (FA). 5-FU 370 mg/m2/day was administered for 5 consecutive days as an intravenous (i.v.) bolus injection preceded by l-FA 100 mg/m2/day with the same administration modality. Treatment was given every 4 weeks until progression. 79 patients were evaluable for toxicity and 64 for response. 2 patients (3%) achieved a complete remission and 8 (12.5%) a partial remission, 33 (52%) had stable disease and 21 patients (33%) had progressive disease. Median duration of remission was 32.5 weeks and median survival for all evaluable patients was 64.5 weeks. Substantial to severe side-effects occurred in 39% of patients. Dose-limiting toxicity (grade 3-4) was mainly diarrhoea (18%) and mucositis (15%). Nausea/vomiting, cutaneous toxicity, leucopenia, alopecia and conjunctivitis of grade 3-4 occurred respectively in 6, 4, 2.5, 1 and 1% of cases. Toxicity appeared to be substantially similar to that characteristic of combined 5-FU and the chiral mixture of d,l-FA. Efficacy was within the range of that observed with the 5-FU/d,l-FA combination, although at the lower level. PMID- 8204358 TI - Oral contraceptives and prognosis in breast cancer: effects of duration, latency, recency, age at first use and relation to parity and body mass index in young women with breast cancer. AB - The aim of this study was to examine associations between oral contraceptive (OC) use, body mass index (BMI = weight/height2) and prognosis in invasive breast cancer diagnosed before the age of 45. Survival analyses of a consecutive sample of breast cancer patients were undertaken. The cases were initially registered in a nationwide case-control study of OC use and risk of premenopausal breast cancer in Sweden and Norway. All 422 cases were under 45 years of age at diagnosis, and recruited from the reports to cancer registries (Sweden) or from surgical departments (Norway) during May 1984 through May 1985. Detailed information about OC exposure was obtained in the initial face-to-face interview. With Cox's proportional hazards analyses, a significantly lower hazard rate [relative hazard (RH) = 0.54; 0.31-0.94] was seen in short-term users (< 4 years)--but not in long term (> or = 4 years) users--than in never-users of OC. Non-significant estimates for RHs lower than 1.0, i.e. better prognosis, with long recency (> 5 years) and latency (> or = 10 years) of OC use were noted. Prognosis was not influenced by age at first OC use or of its timing in relation to the first pregnancy. A higher BMI was associated with a poorer prognosis, RH 5.9 (2.0-17.8) for BMI > or = 29 versus BMI < 19, but BMI was not a confounder or an effect modifier of the association between OC use and prognosis. This study does not indicate that OC use prior to the diagnosis of breast cancer has any adverse effect on the prognosis, at least not in women under 45 years of age at diagnosis. PMID- 8204359 TI - Production of monoclonal antibodies recognising the peptide core of MUC2 intestinal mucin. AB - A peptide based on the tandem repeat sequence of MUC2 mucin was used to produce a series of monoclonal antibodies (MAb). The fine specificity of these antibodies and their implications for MUC2 expression are presented. Three of the MAbs, 996/1, 996/7 and 995/25, were specific to the MUC2p and failed to bind to peptides based on the MUC1,3,4 tandem repeat sequences whereas three others, 994/152, 994/91 and 996/36, cross reacted with the MUC2p and the MUC3 tandem repeat peptide but not the MUC1 and MUC4 peptides. An antigen, affinity purified from a colorectal tumour on one of the MUC2p-specific MAbs, 996/1, was shown to be a high molecular weight polydisperse, mucin-like antigen. Two of the MAbs, 996/1 and 994/152, recognised MUC2 in tissue sections, although the fine specificity varied between the two MAbs, with 994/152 strongly staining gastric, ileum and kidney epithelia, and MAb 996/1 intensely staining colon, liver and prostate tissues. These antibodies also stained a colorectal cell line, and MAb 994/152 also stained a gastric and an ovarian cell line. Six of the MAbs were used to stain colorectal tumour and adjacent 'normal' colonic mucosa sections. All six stained normal mucosa, but only two of the MAbs, 996/1 and 994/91, stained tumour tissue. The staining probably reflects exposure of cryptic epitopes due to varying levels of glycosylation in different tissues. These anti MUC2p MAbs may help in determining the normal role of MUC2 mucin and how it is subverted in malignancy. PMID- 8204360 TI - Folate binding protein distribution in normal tissues and biological fluids from ovarian carcinoma patients as detected by the monoclonal antibodies MOv18 and MOv19. AB - Folate-binding proteins (FBP), which are molecules relevant in folate metabolism, are overexpressed in ovarian carcinomas, as detected by the monoclonal antibodies (MAb) MOv18 and MOv19, which recognise two different epitopes of the gp38/FBP. In this paper, features of the FBP such as the distribution on normal tissues and the release in biological fluids of normal and tumour origin have been investigated. Immunohistochemical analyses on frozen sections of normal tissues showed the presence of the gp38/FBP on some epithelia. The reactivity of both the MAb on Fallopian tubes was intense and comparable to that observed on ovary carcinoma sections. The kidney, bronchial glands, alveolar epithelium of the lung, oesophagus, stomach, pancreas, breast and thyroid showed different levels of staining. By MOv18/MOv19 double-determinant immunoradiometric assay (DDIRMA), the gp38/FBP was found in soluble form in ascitic fluid, serum and urine of nude mice in which the human ovary carcinoma cell line IGROV1 grew as ascitic carcinomatosis. In human biological fluids, the gp38/FBP was detected in ascites of 60% of ovarian carcinoma patients, and in 29% of those with other carcinomas, but not in patients with non-epithelial tumours or with other non-tumoral pathologies. The mean serum arbitrary units (a.u.)/ml values of ovary carcinoma patients were significantly different to those of healthy donors or patients with endometriosis (P < 0.005 and P < 0.01, respectively), but not when compared to the sera of lung carcinoma patients. In addition, the sensitivity of DDIRMA was poor, since only 24% of the ovary carcinoma patients were positive with this assay. When a restricted number of cases selected for the presence of tumour cells in the ascites was examined, the percentage of DDIRMA-positive sera and ascites rose to 41 and 94%, respectively. In the urine, a strong reactivity was observed in the samples of both normal and tumour origin. PMID- 8204361 TI - C-raf-1 proto-oncogene expression relates to radiosensitivity rather than radioresistance. AB - The transfection of several oncogenes, particularly c-raf-1, into mammalian in vitro cell lines has been reported to be associated with increased radioresistance. We have thus investigated (by scanning photodensitometry of western blots) the phenotypic expression of the c-raf-1, c-myc and c-ras protein products in 19 human in vitro cell lines, whose intrinsic cellular sensitivity to 4 MeV photon irradiation has also been determined. High levels of c-raf-1 proto oncogene product expression did not correlate with increased cellular radioresistance, but rather showed a significant correlation with intrinsic cellular radiosensitivity to photon irradiation for alpha (r = 0.664, P = 0.002), and SF2 (r = -0.655, P = 0.002). There was no significant correlation for the ras family, c-myc or actin. These results conflict with those of previous studies in which transfection of the activated forms of the c-raf-1 oncogene were associated with increased radioresistance, and suggest the possibility that the full length proto-oncogene may influence cellular radiosensitivity in a different manner from that of the activated oncogene. PMID- 8204362 TI - Expression of major histocompatibility class I and class II antigens and intercellular adhesion molecule-1 on operable non-small cell lung carcinomas: frequency and prognostic significance. AB - Major histocompatibility complex (MHC) antigens and adhesion molecules, such as the intercellular adhesion molecule-1 (ICAM-1), appear to play an important role in the immunological recognition and destruction of tumour cells. We, therefore, examined the expression patterns of these proteins on primary tumours of 91 patients with operable non-small cell lung cancer (NSCLC). Applying immunohistochemistry with monoclonal antibody (MAb) W6/32 against a common framework determinant of HLA class I antigens revealed a deficient expression in 33.0% of the cases analysed, while neo-expression of either HLA class II antigens (MAb TAL.1B5) or ICAM-1 (MAb PA3.58-14) was observed in 26.4 or 29.7% of tumours, respectively. Analysis of consecutive tumour specimens indicated that HLA antigens and ICAM-1 were frequently coexpressed. With regard to clinicopathological risk factors, we could demonstrate a preferential expression of those markers in patients with locally restricted and well-differentiated tumours or no lymph node metastases, which was more pronounced in adenocarcinomas than in squamous cell carcinomas. In contrast, the presence versus the absence of HLA antigens and ICAM-1 was not correlated with the rate of tumour recurrence or overall survival in patients with NSCLC. In conclusion, the co-ordinated expression of immunologically relevant cell surface molecules on primary NSCLC is a frequent event that correlates with distinct parameters of favourable prognosis. However, we have no evidence that the immune response facilitated by these molecules can effectively influence the clinical course of the disease. PMID- 8204364 TI - Missense polymorphism (C/T224) in the human cathepsin D pro-fragment determined by polymerase chain reaction--single strand conformational polymorphism analysis and possible consequences in cancer cells. AB - Overexpression of cathepsin D in human breast cancers is associated with a higher risk of relapse and metastasis. Also, pro-enzyme routing is altered in several tumoral mammary cell lines, leading to its hypersecretion. MCF7 cells compared to normal kidney carry a C-->T transition at position 224 in the cathepsin D gene which converts Ala to valine in its pro-fragment. Using polymerase chain reaction single strand conformational polymorphism analysis (PCR-SSCP), the variant T allele frequency was found to be 23-30%, and equally distributed in cancer and normal cells. Six to nine per cent of genotypes were homozygous T/T, 34-41% were heterozygous T/C and 50-59% were homozygous C/C. Moreover, genotypes were identical in 19 out of 20 matched sets of tumoral mammary cells and normal white blood cells from the same patients. Loss of heterozygosity was noted in 1 case. C/T224 transition is thus not due to a somatic event. However, this missense polymorphism might modify procathepsin D secretion and/or maturation in breast cancer cells. PMID- 8204363 TI - N-myc gene copy number in neuroblastoma cell lines and resistance to experimental treatment. AB - The N-myc oncogene is amplified in approximately 30% of neuroblastomas. It is well established that cases of neuroblastoma with amplified N-myc have markedly poorer prognosis than those in which N-myc copy number is not elevated. The mechanism for this association is not known but may be related to cellular resistance to radiation or cytotoxic drugs. Seven human neuroblastoma cell lines were used to investigate the relationship between N-myc copy number or expression and sensitivity to ionising radiation and to cisplatin. N-myc copy number was assessed by Southern blotting and hybridisation using the p-Nb1 probe. The signal produced by DNA from the cell lines was compared with that of single copy N-myc from normal human placental DNA. A range of N-myc copy numbers from 1 to 800 was found. Expression levels of N-myc mRNA were compared by "dot blotting" and subsequent hybridisation to the p-Nb1 probe. Radiosensitivity was assessed by surviving fraction at 2 Gy (SF2) following 60Co gamma irradiation. Values ranged from 0.13 to 0.52. Sensitivity to cisplatin was indicated by comparison of isoeffective concentrations (concentration required to produce 1 log cell kill). These ranged from 7.5 to 13 microM. Cisplatin studies showed a correlation between N-myc copy number (though not expression) and resistance to this drug. If this relationship is causal it may explain why treatment fails in those patients with an elevated N-myc copy number. However, no correlation was found between N myc copy number or expression and sensitivity to radiation. It is possible that N myc amplification confers resistance to some but not all treatments used in the therapy of neuroblastoma. Further investigations along these lines may lead to the identification of agents which are most appropriate for the treatment of neuroblastoma with amplified N-myc gene. PMID- 8204366 TI - Symptoms and signs in metastatic spinal cord compression: a study of progression from first symptom until diagnosis in 153 patients. AB - The symptoms in metastatic compression of the spinal cord or cauda equine are described after a systematic recording of the sequence of symptoms in 153 patients. Radicular pain was predominant in patients with metastases located in the lumbar area, while the severity of motor symptoms was positively correlated with thoracic metastases. The most common initial symptom was radicular pain, followed, with decreasing frequency, by motor weakness, sensory complaints and bladder dysfunction. The progression of motor weakness influenced the probability of establishing the diagnosis of spinal cord compression by stepwise marked increased probability when patients lost gait function or progressed into total paralysis. PMID- 8204365 TI - Phase II trial of anaxirone (TGU) in advanced colorectal cancer: an EORTC Early Clinical Trials Group (ECTG) study. AB - Anaxirone, a rationally synthesised triepoxide derivative, was given to 46 patients with metastatic colorectal cancer. Good risk patients received 800 mg/m2 as a rapid intravenous injection every 4 weeks, whereas poor risk patients received 650 mg/m2. Of 46 patients, 45 were evaluable for toxicity and 42 for efficacy analysis. There were 37/45 patients with poor risk, showing no difference in toxicity as compared to good risk patients. The major toxic effect was myelosuppression with 34% of all patients experiencing grade 3 or 4 leucopenia; thrombocytopenia was less frequent. Locoregional phlebitis occurred in 66% of the patients. There was no objective tumour response to anaxirone in 42 evaluable patients. Only 4 patients achieved stabilisation of the disease lasting maximally up to 248 days. Anaxirone is inactive in metastatic colorectal cancer. PMID- 8204367 TI - Amonafide as first-line chemotherapy for metastatic breast cancer. AB - In a phase II study, 32 patients with advanced breast cancer previously unexposed to palliative cytotoxic chemotherapy were treated with amonafide, 800-900 mg intravenously over 3 h repeated every 4 weeks. Objective response was seen in 8 patients including 1 complete response, 10 patients had stable disease and 14 patients progressed so the overall response was 25% (95% confidence interval, 11 43%). The most frequently encountered side-effects were haematological (granulocytopenia > or = WHO grade 3 was encountered in 7/24 patients at 800 mg/m2 and in 3/8 patients at 900 mg/m2 amonafide) and nausea/vomiting (62%), despite prophylactic use of ondansetron. Non-haematological severe adverse reactions included neurotoxicity WHO grade 3 in 1 patient and orthostatic hypotension WHO grade 4 in another. In summary, the results of this trial suggest a limited therapeutic index of amonafide if used at this dose with this administration schedule. PMID- 8204368 TI - Immunomodulatory agents: the cytokines. PMID- 8204369 TI - Systemic treatment of colorectal cancer. PMID- 8204370 TI - Dose optimisation and intensification of cytotoxics in solid tumours supported by haematopoietic growth factors. PMID- 8204371 TI - Cytokines in clinical cancer treatment trials: methodological aspects. PMID- 8204372 TI - Angiosarcoma of the breast following conserving treatment for breast cancer. PMID- 8204373 TI - Let's stop worrying about pigmented skin lesions in children. PMID- 8204374 TI - Phase I clinical trial of gemcitabine given as an intravenous bolus on 5 consecutive days. PMID- 8204375 TI - Human tumour bank in Croatia: a possible model for a small bank as part of the future European tumour bank network. PMID- 8204376 TI - Bioavailability of oral etoposide in gastric cancer. PMID- 8204377 TI - Why don't we use a "Cavalieri"? PMID- 8204378 TI - [Results of surgical treatment of esophageal cancer (209 cases)]. AB - We present a series of 209 patients with cancer of the esophagus over a 13-year period. Average age was 61.99 years and 87.56% of the patients were male. As for histological type, 59.8% of cases were epidermoid carcinomas and the remaining adenocarcinomas. In 76.55% of cases tumor stage was III or IV. Operability rate was 81.8% and resectability 57.89%. The most frequent resective procedure was oesophagogastrectomy through a right thoracotomy and laparotomy. Reconstruction of digestive continuity was achieved in 86.77% with the stomach; 53.72 of resections were judged to be "radical". Overall postoperative morbidity was 45.61%. Respiratory failure and anastomotic leakage accounted for most of morbidity. Anastomotic leakage was more frequent in patients undergoing bypass, with cervical anastomosis, and when the reconstruction was performed with the colon. Mortality rate was 14.04%, but fell to 7.69% in patients undergoing "radical" resection. Overall 5-year survival was 7.83% and 11.81% in patients undergoing resection. The more relevant prognostic factor was tumour stage; 5 years survival of patients with tumor stage I-II was 27.53%, and 0% for patients with tumour stage II or IV. PMID- 8204379 TI - [Early gastric carcinoma in Uruguay]. AB - This report comprises all early gastric carcinomas (EGCs) submitted to surgery in Uruguay from 1972 to 1989. The EGC definition and type classification have been carried out according to the guidelines of the Japanese Research Society for Gastric Cancer. We have included 25 personal cases and also several other cases on the basis of the information provided by other pathologists. We have had frequent access to the microscopic slides for revision as well. 15 cases were discarded due to inadequacy of sampling of the surgical specimen. 69 EGCs were detected in the surgical specimens of 64 patients. Three patients showed a second independent EGC while one showed three lesions. The most frequent endoscopic types were: type IIc (slightly depressed) 36.2%, type IIc + III (combined type, depressed + ulcerated) 29% and type I (protruding type) 18.8%. Three were classified as minute EGCs (5mm or less in diameter). 39 lesions showed neoplastic cells only in the mucosa (m type) whereas 30 invaded the submucosal layer (sm type). EGC's with a diameter of 10 mm (or less) showed at the microscopical level only two histological types: tubular well-differentiated adenocarcinoma (intestinal type) or signet ring cell carcinoma. When the ratio of EGC's versus advanced carcinomas was studies reviewing the pathological files of the Hospital de Clinicas, we found the EGC percentage increased continuously from 1981 to 1989. The median value was 16.6%. This evidence indicates an improvement in the early detection of gastric cancer concomitant with the better training of endoscopists. However, the medial value decreased to 4.9% when specimens from the whole country were considered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204380 TI - [Endoscopic percutaneous gastrostomy. Experience at a general hospital]. AB - Percutaneous endoscopic gastrostomy is a technique scantly used in Spanish hospitals. Its finality is the nutrition of patients with dysphagia, by avoiding the inconveniences and complications of transnasal feeding tubes. Our group has begun a protocol of endoscopically placed gastrostomies and in this work we present its first series; it includes 23 cases of patients with dysphagia secondary to neurological disorders. We have employed the original "pull technique" from Gauderer and Ponsky and we have used homemade gastrostomy tubes. Only two mild complications were observed (stoma infection). In our experience, this technique is easy and has few complications. Furthermore, if homemade tubes are used, the economic cost is very low. In this paper, beside of communicating our results, we summarize the percutaneous endoscopic gastrostomy technique and the way for constructing the tubes. PMID- 8204381 TI - [Benign tumors of the small intestine]. AB - We reviewed 50 patients with benign tumors of small intestine treated over a period of 15 years. Mean age was 58 years, and 54% of the patients were female. The most frequent location of the tumors was the jejunum (54%). The commonest histological variety was leiomyoma (56%), followed by fibroma (14%). Average size of tumor was 4.8 cm. With regard to clinical data, 20% of the patients were asymptomatic; in the remaining 80% of the patients, abdominal pain, gastrointestinal hemorrhage and abdominal distension were the most frequent symptoms. The mean symptom-diagnosis interval was 2 months. Barium studies, duodenal endoscopy and selective angiography were the most useful diagnostic tools. However, only in 30% of cases the correct diagnosis was reached preoperatively. All patients underwent surgical treatment. The more frequent surgical technique was segmental resection of small bowel (84%). Operative mortality was 4% and morbidity was 10%. Actuarial 5-year survival for all patients was 96%. PMID- 8204382 TI - [Colorectal polyps. Treatment and clinical course]. AB - We report the results of the treatment and follow up of 61 patients with polyps of the colon and rectum, who underwent surgical intervention between 1983 through 1991. The mean age was 56 years (range from 41 to 56 y.) and 53% of the patients were males. The majority of the polyps were located in the anorectal region, n = 32 (52.4%) and sigmoid colon n = 17 (27.8%). Tubular adenomas in n = 38 patients and villous adenoma in n = 19, were the most frequent histological types. We have found polyps with invasive carcinoma in 15 (24.6%) cases. The polyps were resected by transanal resection in 15 patients, by colectomies in 11, and 10 patients underwent colectomy for removal of their polyps. Surgery was indicated when the polyp had a base too wide to be removed by colonoscopy or when malignancy was demonstrated by biopsy. There were 10 (19.6%) recurrences during the first three years of follow up. The histological examination showed malignant changes in 4 polyps. Villous adenomas, n = 7 constituted the histological type with more recurrences. Recurrences were treated by local resection in half of the cases. The morbidity was 9.8% and mortality was 3.3%. Surgery when indicated, allows to obtain free margins from tumor, to determine lymph node involvement and to establish the stage. PMID- 8204383 TI - [Influence of hepatitis C virus infection and human immunodeficiency on the natural history of chronic delta hepatitis]. AB - OBJECTIVES: To analyze the prevalence and clinical significance of HCV an HIV infections among a group of patients with chronic delta hepatitis. METHODS: We have studied the clinical and the histological activity and the serological profile the HBV DNA was analyzed by dot blot and PCR and the HDV RNA by dot blot) in 46 patients with chronic delta hepatitis. These results were correlated with HCV infection (assessed by ELISA-2, RIBA-2 and RT-PCR) and HIV infection (ELISA and immunoblot). RESULTS: HBV DNA and HDV RNA was detected by dot in 28.2% and 71.4% of patients respectively, and by PCR, 89.1% of patients had HBV DNA in their serum. Twenty two of 46 patients with chronic delta hepatitis were anti-HCV positives (with HCV RNA detectable in sera by RT-PCR in 19 cases). Anti-HIV positivity was detected in 19 of 46 patients. The mean aminotransferase level, histological activity and serological profile was similar in the anti-HCV positive and negative patients. Likewise, clinical and histological activity and serological profile was similar in the anti-HIV positive and negative patients. CONCLUSIONS: Concomitant infection with HCV or HIV does not seem to significantly modify the clinical course of chronic delta hepatitis. In addition, no significant serological difference has been noted in patients with chronic delta hepatitis with anti-HIV or anti-HCV antibodies. PMID- 8204384 TI - [Granular cell tumor of the esophagus]. AB - We report a new case of granular cell tumor (GCT) is a benign neoplasm in the esophagus (a rare location of which there are only described 80 cases. The tumor was diagnosed in a man aged 55 by endoscopy (asymptomatic from the esophagus point of view) during a chronic liver disease survey. The biopsies of the 3 cm polyp suggested a GCT. The patient died and the necropsy confirmed the presence of a submucous tumor with polygonal cells, wide cytoplasm, eosinophil, granular and ovoid nucleus. The cytoplasm granules were positive PAS and a resistant diastase, without signs of malignancy. In our case, the endoscopy resection was not possible because the state of the patient, although it is the most reasonable therapeutic choice in the most cases. PMID- 8204385 TI - [Carcinoma in a long-standing Zenker's diverticulum]. AB - The authors report a case of carcinoma arising in a longstanding Zenker's diverticulum, in a 66 years old man that refused surgical treatment for 25 years. Three months prior to his admission to our hospital, an exacerbation of his dysphagia, which became severe, was observed; and so was regurgitation, with passage to the airway during swallowing or when asleep. The esophagram showed the diverticulum without images suggestive of neoplasm, and with spilling of barium into the tracheobronchial tree. Esophagoscopy was refused by the patient. After surgical diverticulectomy, a thickened area in the inferior portion of the diverticular body was observed, which was histologically reported as a squamous cell carcinoma with pearl formation, involving only the diverticular wall. Complementary radiotherapy with TCT was administered over the esophagus, mediastinum and supraclavicular lymphatic areas, with a total dose of 5000 Cgy. Concomitant chemotherapy with Mitomycin and 5-Fluorouracil was administered. After a 2 year follow-up, the patient is completely asymptomatic. We discuss etiopathogenic factors, clinical manifestations, diagnostic procedures, and therapeutic possibilities. PMID- 8204386 TI - [Digestive hemorrhage caused by duodenal varices]. AB - Duodenal varices are uncommon and are frequently diagnosed late. However, they are a potential cause of massive bleeding, with tendency to relapse. We would like to offer as an example a case diagnosed by means of an endoscopy. A patient without oesophageal varices and with obstruction of the splenic-portal axis and venous calcifications is reported. A diminution in the volume of the duodenal varices with inspiratory movements may help in the differential diagnosis during endoscopy. We emphasize the need of avoiding incorrect maneuvers during endoscopy and the value of ultrasonography and CAT scan to confirm the diagnosis. Sclerotherapy appears to be the best therapeutic approach. Percutaneous embolization and surgery are therapeutic alternatives if sclerosis is not effective. However, in some cases with self-limited bleeding and a low tendency to relapse, as with the patient described herein, a conservative attitude should be selected. PMID- 8204387 TI - [Intraabdominal desmoid tumor associated with Gardner's syndrome]. AB - An intra-abdominal desmoid tumour included in Gardner's syndrome is described. Some aspects of this unusual tumour are reviewed, emphasizing the value of CT to evaluate shape, location, size and relation with adjacent structures and therefore to decide the therapeutic plan, to avoid the need for exploratory laparotomies which are, moreover, so inadvisable in these patients. Although the, treatment of choice is surgery, it must be performed in accordance with CT findings. When surgery is not possible is incomplete or after recurrences, alternative methods are recommended. PMID- 8204388 TI - [Granular cell tumor of the bile duct: an infrequent location]. AB - We report a case of granular cell tumor of the cystic duct. We have found only 47 such tumors of the biliary tract reported in the literature. Main symptoms at presentation are abdominal pain or obstructive jaundice. The clinical diagnosis is often difficult and the differential diagnosis is established with other more frequent conditions, including malignant neoplasms. Surgical excision is curative. PMID- 8204389 TI - [Neuroendocrine tumor associated with acute pancreatitis]. AB - Neuroendocrine pancreatic tumors are uncommon neoplasms. They may remain symptomless for years, and are usually of late diagnosis. A women presenting with severe acute pancreatitis diagnosed as a neuroendocrine tumor after study by the pathologist of the tissue excised at laparotomy is presented. PMID- 8204390 TI - [Giant single cyst of the liver]. PMID- 8204391 TI - [Acute pancreatitis caused by cisplatin and vindesine]. PMID- 8204392 TI - Noninvasive identification of left main and three-vessel coronary artery disease by thallium-201 single photon emission computed tomography during adenosine infusion. AB - Advanced coronary artery disease, defined as left main or three-vessel coronary disease, was identifiable noninvasively by means of adenosine Tl-201 single photon emission tomography. Among 75 consecutive patients with angiographically documented coronary artery disease, there were 11 patients with the presence (group 1) and 64 patients with the absence (group 2) of advanced coronary artery disease. The lung-to-heart ratio (L/H ratio) of Tl-201 uptake was calculated as the fraction of average Tl-201 counts per pixel in the lung divided by those in the myocardium. The left ventricular dilation ratio (LVDR) was determined as a ratio of left ventricular cavity size in the early image to that in the delayed image. The patients in group 1 had more defects (2.3 +/- 0.6 seg. vs. 0.9 +/- 0.7 seg., p < 0.001), a higher L/H ratio (35 +/- 4% vs. 28 +/- 5%, p < 0.001) and a higher LVDR (1.13 +/- 0.04 vs. 1.06 +/- 0.04, p < 0.001) than those in group 2. The diagnostic accuracy of the identification of advanced coronary artery disease was 89% by perfusion defects, 68% by L/H ratio and 81% by LVDR. Stepwise discriminant analysis revealed that LVDR (F = 36.2, p < 0.0001) and perfusion defects (F = 8.9, p < 0.004) were the significant and independent discriminators of advanced coronary disease. Identification of patients with left main or three vessel coronary disease was enhanced by additional analysis of cavity dilation of the left ventricle and increased Tl-201 activity in the lung. PMID- 8204393 TI - 11C-labeled 2'-iododiazepam for PET studies of benzodiazepine receptors: synthesis and comparison of biodistribution with its radioiodinated compound. AB - For PET studies of benzodiazepine receptors, N-11C-methyl-2'-iododiazepam (2' IDZ) was synthesized by N-methylation of its desmethyl derivative with 11C-methyl iodide, and was subsequently purified by HPLC. The labeling and purification procedures were completed within 45 min after 11C-methyl iodide trapping, and the radiochemical yield (corrected for decay) was approximately 40% based on the initial trapped radioactivity of 11C-methyl iodide. Biodistribution studies in mice demonstrated that 11C-2'-IDZ was rapidly and noticeably accumulated in the brain, and subsequently decreased with time. Accumulation was greater in the cortex than in other brain regions. When compared with 125I-2'-IDZ, the distribution was almost the same until 5 min after injection, but levels were low after 20 min. Metabolic studies indicated that the difference between these two compounds in the time course of brain radioactivity distribution may be due to N demethylation in vivo. PMID- 8204394 TI - Radioimmunoscintigraphy of colorectal cancer with technetium-99m-labeled murine anti-carcinoembryonic antigen monoclonal antibody in athymic nude mice. AB - Technetium-99m(Tc-99m) is an ideal radionuclide for clinical use. A murine monoclonal antibody (Mab) designated F33-104 binds to specific parts of carcinoembyronic antigen (CEA). In the present study, intact Mab F33-104 was labeled with Tc-99m, and the immunoreactivity and biodistribution of Tc-99m labeled F33-104 were studied in athymic nude mice bearing human colorectal cancer xenografts. Mab F33-104, reduced under optimal conditions, was quickly and stably tagged with Tc-99m without loss of immunoreactivity. Higher tumor uptake of Tc 99m-labeled F33-104 was noted in the biodistribution, resulting in a higher localization index and specific-to-non-specific tumor ratio than those of radioiodinated F33-104. These results suggest the potential of Tc-99m-labeled Mab F33-104 for the radioimmunoimaging of colorectal cancer. PMID- 8204395 TI - Value of thallium-201 early reinjection for assessment of myocardial viability. AB - To assess the efficacy of early reinjection for predicting post intervention improvement in thallium-201 (T1) uptake and regional wall motion, we reinjected a small dose of T1 following post-stress imaging and obtained reinjection early images (10 min after early reinjection) and reinjection delayed images (3 hr afterwards) in 40 patients who were referred to us for revascularization (group I). Twenty-nine patients in group I also underwent conventional stress redistribution T1 scintigraphy (group II). Conventional stress-redistribution T1 scintigraphy was repeated after intervention. Contrast left ventriculography was performed before and after intervention and changes in regional wall motion were assessed in 22 of 40 patients. In group I, the predictive value for improvement and no improvement (the accuracy) of reinjection early images in perfusion was 83%, while that of reinjection delayed images was 91%. Furthermore, the accuracy of reinjection early images in regional wall motion was 80%, while it was 91% for reinjection delayed images. In group II, the accuracy in perfusion was 78% and the value in regional wall motion was 70%. Both accuracy in perfusion and in regional wall motion obtained from reinjection delayed images were significantly higher than the values in group II (p < 0.05). These data suggest that early reinjection is useful for predicting postintervention thallium uptake and regional wall motion. PMID- 8204396 TI - Total body and regional bone mineral content in hemodialysis patients. AB - Bone mineral content (BMC) in the total body and lumbar spine was evaluated in 126 hemodialysis patients (60 males, 66 females) by dual photon absorptiometry with the Norland DBD 2600. Measurements of: 1) total body BMC divided by lean body mass (BMCTB/LBM), 2) bone mineral density (BMD) of total body, 3) BMD of four regional sections (head, trunk, pelvis, and legs), and 4) BMD of lumbar spine, generally showed a significant decrease in the hemodialysis patients compared to the reference population. However, arm BMD did not show a significant difference between patients and control populations. The z-score of BMCTB/LBM declined significantly throughout the duration of hemodialysis, although that of the lumbar spine BMD did not. It should be noted that the degree of decrease in BMC was more prominent in the total body measurement than in the lumbar spine measurement. There was preferential osteopenia of the total body in the hemodialysis patients. Although the lumbar spine BMD showed a lower value than the control population, the lumbar spine is not the recommended region to monitor the BMD change in hemodialysis patients. PMID- 8204397 TI - Combined study with I-123 fatty acid and thallium-201 to assess ischemic myocardium: comparison with thallium redistribution and glucose metabolism. AB - To assess the clinical value of combined SPECT imaging with I-123-15-(p iodophenyl)-3-methyl pentadecanoic acid (BMIPP) and thallium-201 (Tl), the findings were compared with those obtained in a stress Tl study and positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG) in 22 patients with myocardial infarction. In 20 patients who underwent a stress Tl study, among 75 hypoperfused segments, 27 segments exhibited less BMIPP uptake than Tl (discordant segments), and the remaining 48 segments showed a similar decrease in BMIPP uptake (concordant segments). Twenty-two of 27 discordant segments (81%) exhibited redistribution on stress Tl study. On the other hand, only one of the 48 concordant segments had redistribution (p < 0.001). In 10 patients who underwent a FDG PET study, among 33 hypoperfused segments, seven segments were discordant segments, and the remaining 25 segments were concordant segments. Seven of the eight discordant segments (88%) demonstrated an increase in FDG uptake. In contrast, only five of 25 concordant segments (20%) showed increase in FDG uptake (p < 0.01). Thus, the segments showing discordant BMIPP uptake are considered to be ischemic but viable myocardium. We conclude that combined imaging with BMIPP and Tl is a useful mean for evaluating tissue viability in patients with coronary artery disease, but it may underestimate the extent of tissue viability, compared with FDG PET imaging. PMID- 8204398 TI - On clinical usefulness of Tl-201 scintigraphy for the management of malignant soft tissue tumors. AB - The purpose of this study was to investigate Tl-201 as a tumor scanning agent in patients with malignant soft tissue sarcomas and to establish the sensitivity of this type of scintigraphy concerning local recurrences or metastases that may remain clinically suspected. Seventy-eight patients with malignant soft tissue sarcomas and 22 with benign soft tissue tumors were studied. Of these 78 malignant soft tissue sarcomas patients, the sensitivity of Tl-201 (81.2%) was higher than that of Ga-67 (68.8%). Thirty-three out of 78 patients received a total of 95 consecutive scintigraphic follow-up examinations. Therapeutic effects was assessed by comparing the results of Tl-201 examinations with the clinical findings. Of these 33 patients, the therapeutic effects observed were as follows: complete remission 1, partial remission 8, progress of disease 1, and no remarkable change 23. Tl-201 scintigraphy has proved itself very useful not only in clinically detecting the malignant soft tissue sarcomas and in assessing therapeutic effects on these diseases, but also in assessing the follow-up patients with malignant soft tissue sarcomas. PMID- 8204400 TI - Cardiac involvement of progressive muscular dystrophy (Becker type, Limb-girdle type and Fukuyama type) evaluated by radionuclide method. AB - Tl-201 SPECT and Tc-99m-Human serum albumin (HSA) multigated radionuclide ventriculography were performed on 11 patients with progressive muscular dystrophy (Becker type 2, Fukuyama type 2, Limb-girdle type 7) to evaluate myocardial involvement. Hypoperfusion was detected in 8 patients on Tl-201 SPECT. Decreases in both systolic function (left ventricular ejection fraction; LVEF) and diastolic function (peak filling rate; PFR) were also seen in these patients. A high incidence of myocardial involvement of these kinds of progressive muscular dystrophy was suggested. PMID- 8204399 TI - I-123 IMP scintigraphy in two patients with primary pulmonary malignant lymphoma. AB - 123I-IMP lung scintigraphy was performed in two patients with primary malignant lymphoma, whose radiographic features were difficult to differentiate from inflammatory or atelectatic lesions. 123I-IMP scans revealed a defect in the lesions on the delayed (24 hr) image, suggesting a tumorous lesion. 123I-IMP scan may contribute to differential diagnosis of this rare tumorous entity from benign disorders having a different appearance. PMID- 8204401 TI - Autoradiographic analysis of [14C]deoxy-D-glucose in thyroid cancer xenografts: a comparative study with pathologic correlation. AB - An experimental model of thyroid cancer was prepared for evaluating the accumulation of [14C]deoxy-D-glucose ([14C]DG) in thyroid cancer xenografts (AC2). A continuous cell line established from a biopsy specimen of a metastatic thyroid carcinoma possessed the ability to synthesize the cellular protein without increase in cell division after adding bovine TSH in vitro. The histological sections of the xenografts resected from the 131I treated nude mice mainly consisted of structures showing follicular and trabecular growth. Immunohistochemically the cytoplasm of the tumor cells was positive for human thyroglobulin(hTg). These observations provide strong evidence that the AC2 cell originates in the thyroid follicular epithelium. By comparing autoradiographic accumulation patterns of [14C]DG and histopathological examinations, it was found that the uptake of [14C]DG was higher in the granulation tissues surrounding necrosis than in viable tumor cells of trabeculary growing and follicle forming tissues. It is suggested that the degree of [14C]DG content reflects not only tumor cell viability and proliferation but also the inflammatory and degenerative reaction accompanying tumor cell growth. PMID- 8204403 TI - Radioimmunoscintigraphy of CEA/CA 19-9 producing tumors with I-131 labeled monoclonal antibodies. AB - A total of 7 (4 males and 3 females) patients were included in this retrospective study to determine the sensitivity of radioimmunoscintigraphy with I-131 labeled anti CEA/CA 19-9 monoclonal antibodies. Out of 7 patients 2 had ascending colon cancer, one had sigmoid colon cancer, one had rectal cancer and one had adenocarcinoma in the CBD and the remaining two had metastatic tumor (one in the lungs and the other in the liver). Whole body as well as spot images showed a 72% (5/7) positive scan. But post operative specimen counts and imaging showed a high tumor to non-tumor ratio and a good tumor to non-tumor contrast of activity of I 131 labeled monoclonal antibody. We did not find any relation between CEA/CA 19-9 levels and scan findings. A case of liver metastasis was also detected by this radioimmunoscintigraphy. PMID- 8204402 TI - 99mTc labeling white blood cells with a simple technique: clinical application. AB - Several radionuclides and different methods have been employed as cellular labels to study inflammatory sites in man. Here we present the results obtained with white blood cells (WBC) labeled with 99mTc using a simple and low cost new technique (SnTec). WBC were incubated with 12 micrograms/ml of stannous chloride for 10 min at room temperature. Then 99mTc was added. After 10 min, the 99mTc labeled WBC were washed and injected into the patient. Comparison studies with 99mTc-labeled WBC using the HMPAO technique were carried out in patients with suspected osteomyelitis. Since the results are similar with both methods, we suggest the use of SnTec to label WBC, in cases of inflammatory diseases. PMID- 8204405 TI - Head surface digitization and registration: a method for mapping positions on the head onto magnetic resonance images. AB - We have developed a method for mapping positions on the head, such as anatomical landmarks, electrode locations, and stimulation sites, onto magnetic resonance (MR) images of the head. This method is based on the registration of two representations of the head surface: a series of contours obtained from MR images and a set of points measured from the head. The three-dimensional coordinates of each head point were acquired with the use of a magnetic digitizer, whose source was removed from the equipment and mounted on top of the subject's head. This arrangement seemed less uncomfortable for the subject than head immobilization and allowed the acquisition of many points without compromising the precision of the measurements. The digitized head surface was registered to MR image head contours using a surface registration algorithm. The registration provided the rotation and translation parameters needed for mapping head positions onto MR images. The precision of this mapping method has been estimated to be in the range of 3 to 8 mm. This method has been used to map dipole sources in electroencephalography and magneto-encephalography and to impose maps of scalp sites used in transcranial magnetic stimulation onto MR and PET images of the brain. PMID- 8204404 TI - Cortical magnetic and electric fields associated with voluntary finger movements. AB - Multichannel recordings of both movement-related magnetic fields (MRMFs) and movement-related cortical potentials (MRCPs) were simultaneously recorded in association with voluntary unilateral self-paced index finger abduction movement in two normal volunteers. 1) Slow magnetic field (readiness field; RF) can be detected several hundred msec before the movement onset, and its field distribution indicates the existence of the largest generator source over the contralateral primary motor area. Taken together with the vertex-maximal Bereitschaftspotential which corresponds to the earlier part of the RF, the complexity of this magnetic field suggested by relatively low correlation value in single dipole model indicates the co-activation of other underlying generators besides this largest dipole. 2) The utilization of MRMF with MRCP facilitates the separation of two distinct electrophysiological events in proximity to the movement onset, which are difficult to be determined by the technique of MRCP only. Those are the motor field (MF) and the movement evoked field I (MEFI) in MRMF, and the parietal peak motor potential (ppMP) and the frontal peak motor potential (fpMP) in MRCP, which occur approximately 20 and 100 msec after EMG onset, respectively. These two subcomponents may imply the culmination of motor cortex and sensory feedback activation, respectively. Combined study of MRMF and MRCP will provide better definition of cortical events related to voluntary movement than the study of either modality alone. PMID- 8204406 TI - Surface energy, its density and distance: new measures with application to human cerebral potentials. AB - In this paper, we propose three new measures for topographic studies of event related potentials (ERP) called the surface energy (SE), its density (SED) and the distance of surface energy density fields (DSED) based on the entire scalp current density (SCD) field. These measures have a specific physical meaning, are free of the reference electrode and any physical conductive model of the head. They capture not only spatial properties, but also continuous time elements present and smeared in the original scalp potential records. They provide a common base for comparisons of recorded potentials among different time points, subjects, regions on the scalp, or experimental conditions. We also construct a statistical inference based on these new measures, and provide an application to human event-related potentials in a visual short-term memory experiment. PMID- 8204407 TI - An exact statistical method for comparing topographic maps, with any number of subjects and electrodes. AB - Statistical methods for testing differences between neural images (e.g., PET, MRI or EEG maps) are problematic because they require (1) an untenable assumption of data sphericity and (2) a high subject to electrode ratio. We propose and demonstrate an exact and distribution-free method of significance testing which avoids the sphericity assumption and may be computed for any combination of electrode and subject numbers. While this procedure is rigorously rooted in permutation test theory, it is intuitively comprehensible. The sensitivity of the permutation test to graded changes in dipole location for systematically varying levels of signal/noise ratio, intersubject variability and number of subjects was demonstrated through a simulation of 70 different conditions, generating 5,000 different data sets for each condition. Data sets were simulated from a homogeneous single-shell dipole model. For noise levels commonly encountered in evoked potential studies and for situations where the number of subjects was less than the number of electrodes, the permutation test was very sensitive to a change in dipole location of less than 0.75 cm. This method is especially sensitive to localized changes that would be "washed-out" by more traditional methods of analysis. It is superior to all previous methods of statistical analysis for comparing topographical maps, because the test is exact, there is no assumption of a multivariate normal distribution or of the correlation structure of the data requiring correction, the test can be tailored to the specific experimental hypotheses rather than allowing the statistical tests to limit the experimental design, and there is no limitation on the number of electrodes that can be simultaneously analyzed. PMID- 8204409 TI - The surface Laplacian, high resolution EEG and controversies. AB - The surface Laplacian estimate (i.e., current source density) as obtained with spline functions is evaluated in the context of some recent controversies concerning high resolution EEG and source localization. In simulation studies, the spline-Laplacian provides much better estimates of cortical surface potential than is obtained from raw scalp potential, provided dense electrode arrays (e.g., 64 or more electrodes) are used. Spline-Laplacians (which are relatively independent of volume conductor model) provide estimates of cortical potential distribution which are quite similar to those obtained with a cortical imaging algorithm based on a four sphere model. PMID- 8204408 TI - High resolution quantitative EEG analysis. AB - High resolution spectral methods are explored as an alternative to broad band spectral parameters (BBSP) in quantitative EEG analysis. In a previous paper (Valdes et al. 1990b) regression equations ("Developmental surfaces") were introduced to characterize the age-frequency distribution of the mean and standard deviation of the log spectral EEG power in a normative sample. These normative surfaces allow the calculation of z transformed spectra for all derivations of the 10/20 system and z maps for each frequency. Clinical material is presented that illustrates how these procedures may pinpoint frequencies of abnormal brain activity and their topographic distribution, avoiding the frequency and spatial "smearing" that may occur using BBSP. The increased diagnostic accuracy of high resolution spectral methods is demonstrated by means of receiver operator characteristic (ROC) curve analysis. Procedures are introduced to avoid type I error inflation due to the use of more variables in this type of procedure. PMID- 8204410 TI - Optimal electrode placements for adequate spatial sampling of auditory evoked potentials. AB - When evoked responses are used in clinical practice and research the measures that are most commonly considered are the latencies and amplitudes of EP components as measured at a single electrode site. Our recent studies have shown that multichannel recordings yield measures such as potential field asymmetry that may be as important as component latency and amplitude. The purpose of this short technical note is to suggest that electrode placement is critical for demonstrating interesting features of the potential field topography, specifically, bilateral, homologous generator sites. The cortical imaging technique (CIT) was used to analyze the averaged responses for a group of thirty normal young adults to a repeated tone and a random oddball tone. Recordings were obtained at 28 scalp recording sites which included 20 placements from the 10-20 system and eight additional sites. Simulated cortical maps were derived for four components, the N1 frequent response and the N2a, P3, and N3, rare minus frequent responses for three different electrode arrays. These arrangements included the full 28-channel array, a 20-channel array that excluded eight additional central sites, and a 20-channel array that included the eight additional sites and excluded peripheral sites. This study demonstrates that for these auditory paradigms, the placement of the electrodes is critically important for discriminating important features of the potential fields. PMID- 8204411 TI - The international 10-20 system revisited: cartesian and spherical co-ordinates. AB - Methods like dipole source localization require an exact specification of the co ordinates of electrode positions. Different values for the co-ordinates of F3, F4, P3 and P4 are encountered in literature. This is due to the unexpected complexity of the calculations involved and aggravated by an inaccurate but widely used control procedure for the placement of these electrodes. We present a table of co-ordinates for the 10-20 system together with a method for determining the co-ordinates of mid-way positions within the 10-20 system. The consequence of using erroneous co-ordinates on the accuracy of dipole source localization is discussed. PMID- 8204412 TI - Spatiotemporal study of Bereitschaftspotential and event-related desynchronization during voluntary movement in Parkinson's disease. AB - Bereitschaftspotential (BP) and Event-Related Desynchronization (ERD) were simultaneously recorded during a voluntary wrist flexion in 10 patients with Parkinson's disease (PD) treated with L-Dopa therapy and 10 control subjects. BP and ERD were analyzed 2 s before and 0.5 s after the movement, during two successive left and right experimental conditions. ERD (9-11 Hz) was computed from 11 source derivations (frontocentral, central, parietocentral). The BP was averaged from these 11 electrodes. For the BP, no spatiotemporal difference was found between the two groups. BP began bilaterally over the 3 groups of electrodes, 1250 ms before movement onset for the right flexion and 1500 ms for the left flexion. A contralateral predominance appeared 500 ms before movement onset over the central area. ERD began in the control group 1750 ms before movement over the contralateral central area, and then appeared bilaterally after its execution. In the PD group, the ERD appeared with a shorter latency than in the control group, 1250 ms (left flexion) and 1000 ms (right flexion) before movement onset; diffusion over the ipsilateral side was found 500 ms before movement onset. ERD also involved the frontocentral area and could be interpreted as a compensatory activity of the supplementary motor area. These findings suggest that with Parkinsonian and control subjects, ERD gives additional and maybe more information than the BP about changes of cortical activity during the motor preparation period. In the PD group the delay of ERD appearance seems to confirm that the programming of movement would be affected, thus explaining partially akinesia. PMID- 8204413 TI - 2nd German EEG/EP Mapping Meeting. Giessen, September 10-11, 1993. Abstracts. PMID- 8204414 TI - Chiral assay methods for lifibrol and metabolites in plasma and the observation of unidirectional chiral inversion following administration of the enantiomers to dogs. AB - Lifibrol, a new drug for the treatment of hypercholesterolemia, contains a stereogenic center bearing a secondary alcohol group. A normal-phase achiral chiral HPLC separation of the enantiomers of lifibrol and two of its metabolites was developed and validated for quantitation in dog plasma. A silica and a Chiralcel OD-H column were operated in series and all six enantiomeric components and internal standard were directly separated. An initial solid-phase extraction (phenyl) clean-up step and a column-switching step to eliminate late-eluting compounds were also utilized. The solid-phase extraction step was automated using a robotic system. Assay development, validation, and application of the method to a bioavailability study of the racemate and enantiomers of lifibrol in dogs are described. The lower limit of quantitation was 0.0125 microgram/ml for each enantiomer of lifibrol using 200 microliters of dog plasma with UV detection (255 nm). In dog plasma following oral or intravenous administration of the racemate, the (R)/(S) ratio of the enantiomers of lifibrol was greater than one and increased with time. Following administration of the individual enantiomers, chiral inversion of the (S)-enantiomer but not the (R)-enantiomer was observed. PMID- 8204415 TI - Diagnosis and monitoring of disseminated candidiasis based on serum/urine D/L arabinitol ratios. AB - Disseminated candidiasis, a devastating disease with high morbidity and mortality in immunosuppressed patients, is difficult to diagnose because of the protean nature of symptoms and the lack of rapid and reliable laboratory diagnostic procedures. The subject of this review is the status of gas chromatographic-mass spectrometric techniques for the determination of D-arabinitol, a unique metabolite of pathogenic Candida species, in serum and urine. The enantiomers are separated by chiral chromatography followed by specific and sensitive detection using chemical ionization and selected ion monitoring. Using D/L-arabinitol ratios, instead of individual concentrations, eliminates the need for knowing the volume of samples and for calibration curves. A new filter paper technique requires only an unmeasured drop of whole blood (venous or finger/heel puncture) or urine; paper spots are mailable. Parallel determinations of D/L-arabinitol ratios in serum and urine in normal subjects and cancer patients with both normal and increased D/L-arabinitol ratios revealed constant (1.2-1.3 range) ratios of serum D/L-arabinitol/urine D/L-arabinitol for all populations studied. Analyzing two body fluids taken at the same time increases reliability by reducing false positives. PMID- 8204416 TI - Current regulatory (draft) guidance on chiral medicinal products: Canada, EEC, Japan, United States. AB - The rapid development of stereospecific analytical, synthetic, and preparative methods has profoundly changed the prospects for development and application of chiral medicinal products. This has induced regulatory agencies, e.g., in Canada, the EEC, Japan, and the United States, to prepare guidance on this subject. The present draft documents are discussed, with emphasis on the two most important cases: (1) New racemates: How many extra requirements are justified? (2) Development of a single enantiomer from an approved racemate: how few are acceptable? At the moment the opportunities for early harmonisation are favourable and the formulation of one international guidance document seems feasible. PMID- 8204417 TI - The effects of desipramine and iprindole on levels of enantiomers of fluoxetine in rat brain and urine. AB - The antidepressant fluoxetine (FLU) and its N-demethylated metabolite, norfluoxetine (NFLU), each contains a chiral center. The combination of FLU and desipramine (DMI), another antidepressant, has been reported to be useful in treatment of depression, to dramatically increase plasma levels of DMI and also to produce more rapid beta-adrenergic receptor down-regulation in brain than caused by DMI alone. We have now begun studies on the effects of this drug combination on the levels of FLU and NFLU enantiomers in the rat. In addition, the combination of FLU and iprindole (IPR) was also investigated. Male Sprague Dawley rats were treated intraperitoneally with either normal saline vehicle, DMI (5 mg/kg/day), (R,S)-FLU (10 mg/kg/day) or DMI (5 mg/kg/day) + (R,S)-FLU (10 mg/kg/day) for 4 days. Following the last treatment, 24 h urine samples were collected. Rats were sacrificed and brains were removed. For the IPR study, rats were pretreated with either saline or IPR-HCl (11.2 mg/kg) and then treated 1 h later with (R,S)-FLU. After 5 h, the rats were sacrificed and brains were removed. Brain and urine samples were analyzed by gas chromatography with electron-capture detection for free (R)-and (S)-FLU and (R)- and (S)-NFLU after extraction and reaction with (-)-(S)-N-(trifluoroacetyl)prolyl chloride. The results from the brains of the rats treated with DMI/FLU indicate that levels of enantiomers of both FLU and NFLU were significantly increased over those seen in the animals receiving (R,S)-FLU alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204418 TI - Species variability in the stereoselective N-oxidation of pargyline. AB - The monoamine oxidase inhibitor pargyline (N-benzyl-N-methyl-2-propynylamine) is known to undergo extensive in vitro microsomal N-oxidation, thought to be mediated predominantly by the flavin-containing monooxygenase (FMO) enzyme system. Formation of the pargyline N-oxide (PNO) metabolite creates a chiral nitrogen centre and thus asymmetric oxidation is possible. This study describes a reverse-phase high-performance liquid chromatographic (HPLC) method for the quantitation of PNO and a chiral-phase HPLC method for the determination of the enantiomeric ratio of PNO. In vitro microsomal N-oxidation of pargyline was found to be highly stereoselective in a number of species, with the (+)-enantiomer being formed preferentially. This metabolic transformation was stereospecific when purified porcine hepatic FMO was used as the enzyme source. PMID- 8204419 TI - Asymmetric metabolic N-oxidation of N-ethyl-N-methylaniline by purified flavin containing monooxygenase. AB - The prochiral tertiary amine N-ethyl-N-methylaniline (EMA) is known to be metabolically N-oxygenated in vitro with microsomal preparations. This biotransformation is thought to be mediated predominantly by the flavin containing monooxygenase (FMO) enzyme system. Microsomal N-oxygenation of EMA is known to be stereoselective and varies between species. In order to further characterise this metabolic transformation, we have examined the in vitro metabolism of EMA using purified porcine hepatic FMO. Following incubation of EMA with purified FMO, EMA N-oxide, the only metabolic detected, was found to be produced stereoselectively [ratio (-)-(S):(+)-(R), ca. 4:1]. The enantiomeric ratio of the N-oxide product did not change markedly with respect to time, enzyme or substrate concentration. Determination of the kinetics of formation of the N oxide indicated a single affinity for the prochiral substrate with differential rates of formation of the enantiomers. The extent of EMA N-oxide formation was shown to be affected by activators and inhibitors of FMO and pH, but its stereoselectively was unaltered. PMID- 8204420 TI - [Yes... but]. PMID- 8204421 TI - [Intestinal anastomosis by biodegradable rings]. AB - During an 9-month period (March to November 1992), six children underwent an intestinal anastomosis by means of a biofragmentable ring (BAR). Patients ages ranged from 5 to 16 years old. There were no mayor complications at surgery. The main technical problems was the difference of size between BAR and intestinal lumen. No patients in which BAR was used have presented fistulae, dehiscence or anastomotical stenosis. PMID- 8204422 TI - [Boix Ochoa's antireflux procedure returns patients to normalcy: 24 hour esophageal pH monitoring of 21 cases]. AB - A great controversy exist concerning the surgical management of gastroesophageal reflux (GER). It is well known that Nissen procedure produces a hypercorrection of the gastroesophageal competency and often a "gas bloat syndrome". On the other hand, the Boix Ochoa's technique is more physiological but corrects GER allowing the persistence of a "radiological" reflux. The aim of the study was to demonstrate the accuracy of this procedure. 287 pediatric patients were studied because of GER and abnormal barium upper gastrointestinal series. 24 hours esophageal pH monitoring was performed in all this patients and in 21 the results were clearly pathological. They were operated on and six months later were new evaluated with upper GI series and continuous 24 hours esophageal pH monitoring. The results were compared with those previous to operation and also with a control group. Statistical great significance was found between presurgical and postsurgical data, what determine the efficacy of the procedure. No statistical significance was found between postsurgical data and the control group, what means that Boix Ochoa's procedure resolve GER without hipercorrection. PMID- 8204423 TI - [Meckel's diverticulum in childhood. Personal experience and actualization]. AB - The authors present 40 cases of Meckel's diverticulum in pediatric patients (average age 6.8 years old). 31 of these (77.5%) were discovered casually in surgery and the other nine (22.5%) presented specific symptoms (three intestinal intussusceptions, three perforations, one hemorrhage, a wet umbilicus and an intestinal obstruction). In this group, seven abdominal radionuclide scan were practiced with 99mTc, resulting in two positive diagnosis (28.5%). All patients were treated with short ileal resection. The histopathological study revealed in nine cases (22.5%) the presence of gastric ectopic mucosa and, in one of them, pancreatic tissue was also found. The only morbidity was a postoperative intestinal obstruction that occurred several months later and that required surgery. The mortality was zero and the average hospital stay was 8.6 days. PMID- 8204424 TI - [Adherence formation following different forms of treatment of peritoneal lesions]. AB - The authors analyse the adhesion forming capacity of various forms of treating a peritoneal lesion. There were four groups each of 10 rats, all receiving the same peritoneal lesion. The control group did not receive any treatment for this injury; in the remaining three, the peritoneal lesion was treated with electrocoagulation, mechanical suture or manual suture. The animals were killed after 30 days, and adhesions quantified using an original method of the authors, which evaluates number, thickness, tenacity, vascularisation and site. Electrocoagulation significantly generated the smallest number of adhesions. The application of suture stimulated the formation of adhesions to a larger extent, manual suture more so than the mechanical method. PMID- 8204425 TI - [Does Bolande's malignant tumor exist?]. AB - Congenital mesoblastic nephroma (CMN) is a rare renal neoplasm which Bolande differentiated from Wilms tumour given its benign nature. We describe 7 cases of CMN which have been treated over the last ten years, in order to highlight to what extent a tumour which is generally considered to be benign can have an aggressive behaviour. 5 patients were diagnosed during their neonatal period (3 of them prenatally) and 2 after the third month of life. Clinical presentation, simple abdominal radiology, echography and abdominal CT scan, which showed characteristic images, led us to a final diagnosis. Tumoral resection was carried out in the 6 typical CMN. The atypical or aggressive CMN was urgently operated under critical circumstances due to spontaneous tumoral rupture. The pathological study showed a CMN of cellular variety with a sarcomatous component. Despite adjuvant chemotherapy, there was a tumoral recurrence which required a surgical second-look and subsequent chemotherapeutical treatment. Bolande's tumour is generally benign, but there is an aggressive cellular variant that fits into the intermediate zone of a pathological spectrum. This aggressive variant have different clinical, radiological and anatomo-pathological features and therefore it involves radical surgical treatment and additional chemotherapy with a rigorous follow-up in the short and the long term. PMID- 8204426 TI - [Simultaneous, bilateral and permanent ventilation with a diaphragm pacing in childhood: the implantation technique and indications]. AB - The acute effects of external stimulation were well demonstrated by the turn of the century, but the chronic application had to wait until the advent of the modern pacemaker technology. Since 1983 we have implanted bilateral diaphragm pacing in ten infants and adolescents with quadriplegia and central hypoventilation syndrome. The preferred site of implantation was the thoracic phrenic nerve. The electrophysiological status of the phrenic nerve function has before been determined in all patients. We have got bilateral and continuous ventilation, in all patients, but, in quadriplegics is necessary a conditioning period. Long term stimulation of the phrenic nerves to pace the diaphragm is an effective method of ventilatory support in selected cases. PMID- 8204427 TI - [The usage of thermo-vac facial masks for the treatment of hypertrophic scars in children]. AB - We present the results obtained in the treatment of facial hypertrophic scars in children admitted in the Pediatric Burn Unit of the Hospital Infantil La Paz (Madrid). During the last 30 months 13 patients, with ages ranging from 3 months to 5 years, have been treated. Compared to the elastic pressure masks, rigid masks have yielded better results both on the short and the long term. Rigid masks of Thermo-Vac material turn out to be more comfortable and easier to wear and tolerate than the classical elastic appliances. PMID- 8204428 TI - [Pubertal idiopathic gynecomastia]. AB - 14 boys with pubertal gynecomastia, aged 9 to 16 years, were presented. Physical assessment, including pubertal maturation, height, weight, bone age, pubic hair stage, testicular and penis calibre and degree of gynecomastia was determined. Sexual steroids, LH-FSH, prolactin, were studied. All patients had psychological stress. 11 patients had been treated surgically by mastectomy with success. PMID- 8204429 TI - [Acute renal failure after major surgery: effectiveness of continuous arterio venous hemofiltration (CAVH)]. AB - Thirteen patients with acute renal failure after mayor surgery were treated with CAVH, 6 children after liver transplantation (OLT) and 7 after extracorporeal cardiac surgery (ECS). The ages ranged from 4 months to 19 years, with filters from 0.16 m2 to 0.5 m2, according to the weights. CAVH was initiated 19 hours (mean) after OLT and 10.5 hours (mean) after ECS. Mean creatinine clearance was 6.3 ml/min/1.73 m2 (ECS) and 10.1 ml/min/1.73 m2 (OLT). Serum creatinine remained under acceptable values (mean 2.1 mg.%) in both groups. Mean fluid removal was 5.7 L/day (242 ml/kg/day), which allowed plasma administration despite oligoanuria in the OLT group. Fluid removal decreased central venous pressure (p < 0.001) and increased mean arterial pressure (p < 0.01) in the ECS group, and inotropic support could be diminished. CAVH was well tolerated and it was maintained for 79 hours (ECS) and 105 hours (OLT). PMID- 8204431 TI - [Surgical management of congenital tracheal stenosis]. AB - A six month old infant with dextrocardia, butterfly vertebrae and oesophageal atresia type I is reported. After surgical repair, she developed respiratory distress, needing ventilatory support. The bronchoscopy and bronchography demonstrated segmental tracheal stenosis. A resection of the stenotic segment was performed, and tracheal reconstruction with terminoterminal anastomosis. After a period of clinical improvement, respiratory distress came back and reestenosis was ascertained locating its level on the anastomosis. Three sessions of balloon dilation were ineffective and because that it's decided the introduction of a metallic self-expandable stent. After a transient relief, the patient had a bilateral pneumonia ending with the dead of the patient. In spite of the treatment used, it was not possible to accomplish solution in a middle or a large place. This constitutes a clear exponent of the complexity in the management of the congenital tracheal stenosis. PMID- 8204430 TI - [Analytic preoperative control and serum alaninaminotransferase (ALT) activity]. AB - A standard model of analytical preoperative profile does not exist, so we decided to perform a wide profile. In this revision, we studied the utility of determining serum ALT activity in analytical preoperative controls, searching for the causes of its elevation in pediatric patients who would undergo minor surgery. Of the 3,750 patients analysed, 1.57% showed elevated serum ALT activity. Searching for the main cause, we found the following groups: I) patients with diseases unrelated to the surgical procedures that cause elevated serum activity; II) patients on pharmacological treatments which may produce transitory elevations of serum ALT activity, and III) patients with elevated serum ALT activity that has no evident clinical or pharmacological cause. The high incidence of patients with this abnormality justified the inclusion of serum ALT activity in the profile. We conclude that: a) the reasons for this elevation should be investigated, b) pediatricians should consider postponing surgery, and c) resumption of normal serum ALT activity should be monitored. PMID- 8204432 TI - [Buccal mucosa free graft for severe hypospadias repair]. AB - We present a boy 6 years old, with a penoscrotal hypospadias and perineal urethrostomy, with several unsuccessful attempts at hypospadias repair in other hospital. Autologous buccal mucosa was used as a free graft for urethral reconstruction. The clinical result was excellent, with a functioning urethra of good caliber throughout the entire length of the penis, without voiding difficulties. A proximal fistula that closed spontaneously 20 days postoperatively was the only complication. We present this technique as an elective option for severe hypospadias repair. PMID- 8204433 TI - [Post-traumatic cholelithiasis]. AB - A 5 year old patient, without any lithogenic antecedent, suffered a trauma, resulting in a shrunken fracture of the left parietal bone, and a splenic parenchymal hematoma. A hemoperitoneum developed at the 3rd postoperation day, with an overall blood loss of 15% of the total blood volume. At the 6th day a well formed biliary calculi was detected in the gallbladder. As the patient remain asymptomatic related to his cholelithiasis, an ultrasound follow-up was instituted. At 3 month postinjury all biliary stones dissolved completely. In this report, the etiopathogenic factors responsible of stone formation in the biliary tree, and current therapeutic recommendations are reviewed. PMID- 8204434 TI - [Acute gastric volvulus associated with diaphragmatic hernia]. PMID- 8204435 TI - [Considerations regarding the treatment of non-aganglionic congenital intestinal neuropathies]. AB - Hyperganglionosis or neuronal intestinal dysplasias (NID) and hypoganglionosis (HO) are intestinal diseases of difficult diagnosis and treatment and diverse evolution, despite identical histologic findings. The aim of this study was to discuss the therapeutic problems derived from the patients differing clinical course. Retrospective review of 14 patients with regard to diagnosis, manometry and histology (hematoxylin-eosin, acetylcholinesterase activity, immunohistochemistry and Smith's silver stain) was done. Six patients presented intestinal occlusion or sub-occlusion from the first months of life with impeded oral feeding. Ileostomy was performed in 5 and total colectomy with anastomosis in 1. All patients required parenteral nutrition; cisapride was added in 2. Three died from sepsis (3 NID). Of the 3 survivors, 2 have ileostomies (2 NID) and the other ileo-rectal anastomosis (NID). Of the remaining patients, two presented aganglionism and the finding of proximal hyperganglionism occurred post-surgery. Surgery was repeated in one patient. The remaining 6 (1 HO, 5 NID) were diagnosed between 3 and 10 years of age because of constipation. Four are under treatment with cisapride and 2 required partial colic resection. No relationship can be established between histologic findings and clinical manifestations. In chronic clinical courses, treatment with cisapride and cleaning enemas should be tried first. Acute clinical pictures (occlusion-sub occlusion) should be treated by decompressive ileostomy. Partial colic resection may lead to new intestinal failure. PMID- 8204436 TI - Pediatric hemato-oncology in India. PMID- 8204437 TI - High-dose methotrexate: is it warranted? PMID- 8204438 TI - Parental anxiety and neuroblastoma screening of infants. PMID- 8204439 TI - Developments in pediatric hematology and oncology in The Netherlands. PMID- 8204440 TI - Screening infants for neuroblastoma: the parents' perspective in false-positive cases. AB - The objective of this study was to ascertain the reactions and experiences of parents whose children were defined as false-positive cases in a research program of screening 6-month-old babies for neuroblastoma. Parents of seven of the eight infants falling into this category participated in the study. Parents of five children described themselves as worried/very worried at the positive result, some contemplating the treatment involved and the possibility that their child could die. Parents waited a maximum of 3 days before the clinical investigations took place. The mother of one child was dissatisfied with the handling of the investigations, reporting a lack of information and little opportunity to discuss questions; she was subsequently more anxious about her child. Parents of two children reported lasting "concerns" that they attributed to neuroblastoma screening. PMID- 8204441 TI - Evaluation of serious adverse events in patients treated with protocols including methotrexate infusions. AB - During the period 1979 to 1992 we treated 141 children for various malignant diseases with protocols including methotrexate (MTX) infusions in doses ranging from 0.5 to 33.6 g/m2. During a total of 922 courses, there were no fatal complications associated with MTX treatment. Serum MTX concentration and pharmacokinetic data were monitored continuously during the infusions. In this study, we evaluated the occurrence of serious untoward reactions to MTX infusions. Impaired renal function with delayed drug elimination was seen in seven patients, all boys, especially after short infusion times. All recovered completely without any serious clinical symptoms. In three leukemia patients who later died from resistant disease, we observed late neurological disturbances and computer tomography (CT) brain scan abnormalities. Pharmacokinetic data from the patients with complications are described and confirm that serial MTX concentration monitoring is the most important early indicator of renal toxicity. PMID- 8204442 TI - Effects of 1,25-dihydroxyvitamin D3 and retinoic acid on the proliferation and cell cycle phase distribution of neuroblastoma SK-N-SH cells. AB - The hormone 1,25-(OH)2D3 has been shown to modulate cell proliferation and induce differentiation in several normal and malignant cell lines. In this work, we examined the effect of the hormone on the neuroblastoma SK-N-SH cell line. The steroid did not influence cell growth and cell cycle distribution, while retinoic acid inhibited proliferation and induced an accumulation of the cells in the G0/G1 phase of the cell cycle. 1,25-(OH)2D3 did not alter cell morphology. The activities of the 1-alpha- and 24-hydroxylases were low and not regulated by the hormone. The level of the total 1,25-(OH)2D3 receptor was low. We conclude that the lack of effect of 1,25-(OH)2D3 on the SK-N-SH cell line is related to the low level of the 1,25-(OH)2D3 receptor. PMID- 8204443 TI - The efficacy of ticarcillin-clavulanate and gentamicin as empiric treatment for febrile neutropenic pediatric patients with cancer. AB - The therapeutic efficacy of ticarcillin-clavulanate and gentamicin was assessed in 56 pediatric cancer patients with 95 febrile neutropenic episodes. The mean temperature of these children on admission was 102 degrees F (range 101 degrees to 106 degrees F), with a median absolute neutrophil count of 60. The median hospital stay was 7 days. All of the patients had one of two types of permanent central lines (Port-A-Cath, N = 75; Hickman, N = 20). Of 20 episodes of bacteremia, 17 had microbial isolates that were gram-positive bacteria and 8 of these episodes required the addition of vancomycin. Clinical cure was achieved in 84 of the 95 febrile episodes (88%) with the use of ticarcillin-clavulanate and gentamicin. There were no fatalities, nor were there any major toxicities. We conclude that the combination of ticarcillin-clavulanate and gentamicin is an effective initial empirical therapy for febrile neutropenic children with cancer. Gram-positive pathogens are the usual cause of breakthrough bacteremia in this clinical setting of central line usage, and associated morbidity and mortality from these organisms are low. PMID- 8204444 TI - Heterogeneity of the erythropoietic defect in two cases of Aase-Smith syndrome. AB - Here we report two children with Aase-Smith syndrome (triphalangeal thumbs and congenital red cell plasia). In vitro growth of erythroid colonies was normal in the first patient and totally absent in the other. In both patients, treatment with glucocorticoids induced remission of anemia. Our results suggest that the different growth patterns of erythroid colonies observed in the two patients could reflect the defect of erythroid differentiation occurring at discrete maturational levels. PMID- 8204445 TI - Non-Hodgkin's lymphoma and Klinefelter syndrome. AB - Patients with a 47, XXY karyotype (Klinefelter syndrome) appear to have an increased risk of developing a malignancy in adulthood, usually cancer of the breast, extragonadal germ cell tumor, and acute nonlymphoblastic leukemia. There is growing evidence to show that these patients also have an increased risk of developing a malignancy in childhood. There are reports describing the development of acute lymphoblastic leukemia, retinoblastoma, and rhabdomyosarcoma in children with a 47, XXY or mosaic 47, XXY/46, XY karyotype. We report a child with a bone metastasizing, B-cell lineage, non-Hodgkin's lymphoma (NHL) who was found to have a 47, XXY karyotype in both the tumor and constitutional cells. PMID- 8204446 TI - Human recombinant granulocyte-macrophage colony-stimulating factor in pediatric oncology practice. AB - This paper reports preliminary experiences with human recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) in children with malignant diseases administered for three indications: (1) chemotherapy-induced neutropenia and sepsis, (2) prolonged neutropenia decreasing dose intensity, and (3) prevention of neutropenia after sublethal doses of chemotherapy. It was concluded that in the daily dose of 5 micrograms/kg subcutaneously, GM-CSF is capable of reducing the duration of chemotherapy-induced neutropenia and may be an effective tool in maintaining dose intensity and achieving dose escalation. PMID- 8204447 TI - Selection of Candida glabrata in pediatric bone marrow transplant recipients receiving fluconazole. AB - We observed an alarmingly high rate (5/16 patients; 31.3%) of orointestinal colonization with Candida glabrata--often in high numbers--in pediatric bone marrow transplant recipients receiving fluconazole as antifungal prophylaxis. This selection is probably due to the intrinsically low susceptibility of C. glabrata to fluconazole. PMID- 8204448 TI - Occurrence of seminoma and dysgerminoma in father and daughter. AB - We report the occurrence of seminoma and dysgerminoma in father and daughter. Both tumors exhibited similar histological appearances. This case supports the concept of a common genetic basis for these germ cell tumors. PMID- 8204449 TI - Imerslund-Grasbeck syndrome coexisting with beta-thalassemia trait. AB - A 9-year-old female patient with Imerslund-Grasbeck syndrome and heterozygosity for beta-thalassemia is presented. At admission the hemoglobin (Hb) was 7.2 g/dL; reticulocytes, 0.2%; red blood cell count (RBC), 2.3 x 10(12)/L; mean corpuscular volume (MCV), 80 fL; hemoglobin A2 (HbA2), 4.3%; fetal hemoglobin intervening sequence (IVS) (HbF), 1.9%. In the bone marrow aspiration smear, megaloblastic changes were observed; the Schilling test was compatible with malabsorption. DNA analysis revealed the presence of heterozygosity for the IVS-I-110 type of beta thalassemia mutation. Five months after treatment with vitamin B12, Hb was found to be 12.8 g/dL; RBC, 5 x 10(12)/L; MCV, 63 fL. PMID- 8204450 TI - Acute lymphoblastic leukemia associated with Klinefelter syndrome. PMID- 8204451 TI - Future manpower needs in caring for an older cancer-patient population. AB - The Minnesota Cancer Surveillance System provides data for almost all cancers newly diagnosed in residents of Minnesota. A statistical method, Population Cancer Risk (PCR), estimates the total number of cancers that will occur in the lifetimes of 1,000 people, based on the Minnesota cancer incidence and life expectancy rates from 1988-1990. The overall PCR is 459 cancers per 1,000 lifetimes of persons born today. By year 2020 the Minnesota population will have increased 12% since 1990, but the total cancer incidence will have increased 60%. As a result, there will be an increased demand for medical oncologists, radiotherapists, and surgical subspecialists. Primary care physicians will play an increasing role in cancer prevention, early detection, therapies, and long term follow-up. Physician's assistants and skilled nurses will add further to patient cancer management. Cancer patients will be older, on average. The future will include changes in the methods of care of the older cancer patients and in economic, social, and bioethical issues involving older persons. PMID- 8204452 TI - Cancer education curriculum at the Louisiana State University School of Dentistry. AB - The cancer education curriculum at Louisiana State University School of Dentistry provides students didactic and experiential learning throughout their dental training. Freshman are presented concepts of early detection of cancer in an oral diagnosis course. Later courses in oral diagnosis, medicine, and pathology include diagnostic and treatment decision making and rehabilitative information. Junior students attend a head-and-neck-tumor board composed of dentists and physicians that decides cancer treatment and rehabilitation. Juniors also participate in a biopsy service that includes observing or performing the biopsy, examining the tissue microscopically, and reporting their findings. Additionally, a required, medical and dental, multidisciplinary course in oral oncology provides instruction in diagnosis, treatment, and rehabilitation of cancer patients. Seniors participate in an oral cancer screening service as part of their community dentistry rotation. The postgraduate dental programs and the dental hygiene programs also participate in this curriculum. PMID- 8204453 TI - Sensitive patient-doctor communications relating to the breasts and prostate. AB - This study was carried out at two primary health care centers in separate counties in central Sweden. Data derive from recordings of consultations of 42 patients and their general practitioners. The patients and the doctors were interviewed separately after each consultation. The analysis is based on the audio-recordings as well as on verbatim transcripts of the consultations. It focuses on communications about the topics relating to the breasts and the prostate and how these topics are dealt with during the consultations. These topics were brought up in seven (29.2%) of the 24 consultations with female patients and four (22.2%) of the 18 consultations with male patients. A common pattern of the outcome as regards information was that the patient was given neither the tool, i.e., knowledge about bodily functions, nor methods for detecting an abnormality. The patients indirectly evinced ignorance with regard to the body, examinations, and diseases, and did not ask any direct questions that required answers. PMID- 8204454 TI - Reading versus comprehension: implications for patient education and consent in an outpatient oncology clinic. AB - Written educational materials and consent forms are often given to patients with little regard for their ability to read them. Nationwide sampling and data from the 1990 census suggest that 10% of U.S. adults are functionally illiterate. In this study, 100 adult patients (64 female, 36 male) seen consecutively in an oncology clinic were tested for reading vocabulary (RD-VOCAB) and reading comprehension (RD-COMP) using the Woodcock-Johnson Psychoeducational Battery. The mean grade levels of education (last grade completed), reading vocabulary, and reading comprehension of all participants were 12.5, 11.3, and 10.5, respectively. The discrepancy between the grade level of education and RD-COMP varied by age, the largest discrepancies being found in the 30-39 (three grades) and 60-69 (2 1/2 grades) age groups. After controlling for educational level, it was found that the mean grade level of RD-COMP was statistically lower than educational level. Statistically assuming all subjects to have completed high school, the mean levels of RD-COMP ranged from ninth grade in the 30-39 age group to twelfth grade in the 40-49 age group. This study underscores the fact that the health professional cannot assume that a patient who has completed a certain grade level in school can read at the corresponding level. Consent forms and other health education materials should be written at least three grade levels lower than the average educational level of the target population. PMID- 8204455 TI - Children who have a parent with cancer: a pilot study. AB - This British pilot study was undertaken to determine whether the children of cancer patients experience problems and anxieties related to the parent's diagnosis and treatment. The data were collected by means of semistructured interviews with 24 adolescent children (16 sons, eight daughters) whose parents' cancers had been diagnosed between two and six years previously (mean four years). Self-report questionnaires to assess adolescent anxiety were also completed at the interviews. The results show that some of the children experienced problems and anxieties related to their parents' cancers that affected their school lives, sports and leisure activities, family lives, and relationships. Factors that were significantly associated with high anxiety scores were: inability to discuss the parent's illness with parents; having to spend less time with friends; having to spend less time on sport and leisure activities; deterioration in schoolwork; and continuing anxiety over the parent's illness. PMID- 8204456 TI - Anxiety in medical situations and chemotherapy-related problems among cancer patients. AB - Relationships between anxiety in medical situations and age, gender, duration of illness, and communication problems with friends or relatives were examined in a heterogeneous sample of 117 adult cancer patients. The relationships between the same demographic, medical, and psychosocial variables and chemotherapy-related problems in a subsample of 79 patients receiving chemotherapy also were examined. Results indicated that females and patients who reported more communication problems with friends or relatives reported more anxiety in medical situations. Female patients and patients who reported more communication problems with friends or relatives also reported more chemotherapy-related problems. Duration of illness was not related significantly to either dependent measure. Clinical implications of these results are discussed. PMID- 8204457 TI - Factors influencing the communication of the diagnosis to patients who have cancer. AB - Medical attitudes and behaviors in communicating diagnoses to patients found to have cancer were investigated in a sample of 126 practitioners in Italy. The research aimed at analyzing the medical approach to oncology patients and how they were provided information about their cancers and relevant treatments. In particular, psychosocial factors influencing the physician's decision whether or not to inform the patient of the diagnosis were examined. The results showed a significant interaction between the working environment and the practitioner's perception of cancer, which can impinge on the decision whether to provide the patient with information. PMID- 8204458 TI - Stimulating cancer screening among Latinas and African-American women. A community case study. AB - Recent studies have attributed underutilization of early cancer detection programs among the disadvantaged to knowledge deficits and myths, lack of belief in cancer susceptibility (denial), and such attitudinal barriers as fear and embarrassment. Video modalities have been demonstrated to be effective in increasing knowledge and promoting health-protective behavior in low-income people of color. Waiting rooms of public health clinic facilities in large urban areas provide a captive audience of predominantly African Americans and Latinos with a preference for obtaining health information from audiovisual media. The development of a culturally sensitive, cost-effective documentary format is described. An experience of rapid acceleration in demand for Pap smears in an underserved Latino community of East Los Angeles following the showing of one of these videos is chronicled as a spontaneous and informal evaluation of this approach to health education/promotion video production. PMID- 8204459 TI - Impact of President Clinton's Health Security Act on residency programs. AB - The Clinton Health Security Act calls for a major shift in the emphasis of medical training. While family practice, general pediatrics, general internal medicine, and obstetrics and gynecology stand to benefit, other specialties will see decreases in their programs and their residency slots. In light of the present sparsity of programs in family practice and the prevalent student disinterest in the specialty, only heroic efforts will make possible achievement of the 55/50 ratio of primary care physicians to other specialists outlined by the Clinton plan. Problems inevitable in the transition are described and incentives for change suggested. PMID- 8204460 TI - Their favorite service. AB - In the face of widespread housestaff disenchantment with serving on oncology wards, the author's oncology consultation service is one of the most popular rotations among housestaff at the hospital. She discusses the factors contributing to the service's success in this regard: 1) focus of teaching efforts on residents; 2) interdisciplinary patient care model; 3) integration of ambulatory care into the rotation; 4) the consultative nature of the service. PMID- 8204461 TI - Adapting undergraduate preclinical courses to changes in clinical applications. AB - The availability of new technologic tools has greatly changed differential diagnosis. To assess the importance of these tools in current clinical practice, the authors determined the frequencies of use of new imaging methods in diagnosis, staging, and follow-up in 71 oncology cases. The new methods were found to have replaced traditional diagnostic procedures to a substantial extent. To familiarize medical students with the new techniques, lectures on sectional anatomy given by radiologists were integrated into traditional anatomy courses for a group of 50 students. Two years later, after their initial exposure to clinical practice, the 42 students remaining in the group answered a questionnaire regarding the usefulness of the sectional anatomy segment of their anatomy training. Of these 42 students, 14 rated the sectional anatomy exposure "very helpful" to comprehension in the clinical internship and 21 rated it "helpful." The students suggested that the program be reinforced by an integrated textbook. This preliminary study suggests that basic preclinical courses should be modulated to reflect new methods that come into routine use in clinical practice. PMID- 8204462 TI - Over 400 years of cancer control efforts in Poland. AB - The history of the struggle against cancer in Poland is presented from its beginning, marked by the first hospital for cancer patients established four centuries ago in Warsaw, to the implementation of the main goal of National Cancer Programmes, i.e., the recent construction of a large, modern Cancer Centre in Warsaw. Among the 100,000 new cancer cases each year in Poland, there are more than 70,000 deaths. In males, cancers most often involve the lung (30.5%), stomach (9.8%), larynx (5.5%), prostate (5.1%), and urinary bladder (5.0%). In females, cancers most often involve the breast (17.5%), cervix uteri (9.8%), lung (6.6%), stomach (6.2%), and ovary (6.2%). The estimated probabilities of five year survival are 26.4% for males and 39.8% for females. Over 100 years of epidemiologic investigation have resulted in a clear epidemiologic picture of cancer in Poland. PMID- 8204463 TI - Electron irradiation slows down wound repair in rat skin: a morphological investigation. AB - To date, there have been few morphological investigations of the effect of electron radiation on the healing of skin wounds in rats. The present morphological study examines the wound repair process in electron-irradiated rat skin by electron microscopy. Standardized, full-thickness, incisional wounds were made in the lower dorsal skin of animals which had been locally irradiated with 9.6 Gy electron radiation 7 days previously. The irradiation dose was maximal at 3 mm depth. Twenty-four rats were used in the investigation; 12 were irradiated and 12 sham-irradiated. Three rats from each experimental group were killed at 1, 3, 7 and 14-day time intervals after wounding. The morphological effect of electron irradiation on the repair of each wound was investigated by light microscopy (LM) and scanning electron microscopy (SEM). New granulation tissue visualized by SEM was quantified using computerized image analysis. The results suggest that a single, partial-body, controlled depth dose of electron irradiation delays wound repair. LM showed that there is a depression of the inflammatory cell and tissue exudate response, slowing of epithelial migration, and a decrease in fibroblast representation, together with a delay in the formation of collagen bundles. Granulation tissue formation was impaired up to 7 days post-wounding, but was restored to around control values by day 14, indicating that healing was delayed. However, as the healing of normal tissue was not prevented, this study supports a preoperative role for the use of low-dose electron irradiation therapy for the treatment of electron-sensitive superficial pathologies in surgical practice. PMID- 8204464 TI - The use of cytology in the diagnosis of basal cell carcinoma. AB - Two hundred and forty patients with basal cell carcinomas (BCCs) on the head or neck were studied. Scrapings of the lesions were taken for cytological examination, and a 3-mm punch biopsy was performed for histopathological study. The accuracy of diagnosis by each method was compared. Both methods confirmed the clinical diagnosis in 226 cases, and both were negative in 10 cases. Cytopathology gave one false negative result (0.42%), and histopathology gave two false negative results (0.83%). Cytopathology gave one false positive result (0.42%), and histopathology did not produce any false positive results. We conclude that cytological examination of skin scrapings from suspected BCCs is a rapid and reliable method of diagnosis. PMID- 8204465 TI - Anti-inflammatory actions of benzoyl peroxide: effects on the generation of reactive oxygen species by leucocytes and the activity of protein kinase C and calmodulin. AB - For many years, benzoyl peroxide has been used as a topical treatment for acne. Although the drug has been shown to interfere with a variety of pathways, believed to be of importance in the aetiopathogenesis of acne, its mechanism of action is thought to be principally antibacterial. Recent circumstantial evidence suggests that protein kinase C might serve as an additional pharmacological target of benzoyl peroxide. In the present study, we investigated the effects of benzoyl peroxide on the release of reactive oxygen species, regulated by protein kinase C and calmodulin, from human neutrophils, a potentially important step in acne inflammation. Micromolar drug concentrations were found to inhibit the release of reactive oxygen species, but there was marked drug-induced cytotoxicity in neutrophils. However, when tested in cell-free assays, benzoyl peroxide displayed marginal inhibition of protein kinase C, but failed to antagonize calmodulin. Further investigations on its mechanism of action revealed non-specific interference with nucleotide binding sites. Therefore, the data presented here indicate that, in contrast with our previous findings with tetracycline derivatives, the clinical anti-inflammatory activity of benzoyl peroxide is unlikely to be mediated by protein kinase C or calmodulin. The differential interaction of drugs with protein kinase C and calmodulin might help to explain their different clinical usefulness in various degrees of acne severity. PMID- 8204466 TI - Assessment of an anti-T-cell receptor variable region antibody panel in cutaneous T-cell lymphoma. AB - Using a panel of seven commercially available monoclonal antibodies directed against specific sites of the T-cell receptor variable region, we have studied the staining patterns in 15 biopsies from 11 patients with cutaneous T-cell lymphoma (CTCL), and in five patients with benign lymphocytic infiltrates. Eight of the 11 patients with CTCL showed staining of the majority of lymphocytes with either V beta 8 alone (n = 3), V beta 12 alone (n = 2) or with both V beta 8 and V beta 12 (n = 3). None of the biopsies from patients with benign dermatoses showed staining of the majority of lymphocytes with any of the antibodies. PMID- 8204467 TI - Naevi in schoolchildren in Scotland and Australia. AB - To test the hypothesis that children living in subtropical and tropical environments have more naevi than those of similar ethnicity living in temperature countries, a comparative study of melanocytic naevi in 111 schoolchildren from Brisbane, Australia, and 222 from Glasgow, Scotland, was carried out. All children were aged 13-15 years, of European ancestry, and had spent most of their lives at latitudes of less than 30 degrees S (Australia) or greater than 30 degrees N (Scotland). Using an identical protocol, all naevi of 2 mm or more in diameter occurring on the right arm were counted by either a highly experienced research nurse in Brisbane, or a dermatologist in Glasgow. Hair and eye colour, and facial freckling, were assessed by the examiner, and axillary skin colour of children in both cities was measured using the same reflectance spectrophotometer. Children in Brisbane had significantly more naevi than those in Glasgow (P < 0.05), after adjusting for complexion variables. The difference in the geometric mean number of naevi on the arm was much greater among boys (7.7 vs. 4.4, in Brisbane and Glasgow, respectively) than among girls (7.3 vs. 6.7). This has parallels with the sex differences in melanoma at later ages in the two countries. Besides country of residence, freckles and innate skin colour were the most significant predictors of large numbers of naevi, whereas red hair had a significant protective effect. Overall, these data on prevalence of naevi in children from contrasting environments provide some evidence in support of the theory that naevus development is related to the level of sun exposure in childhood and adolescence. PMID- 8204468 TI - Improved prediction of the minimal phototoxic dose in PUVA therapy. AB - In an attempt to improve the prediction of PUVA erythemal sensitivity, we have examined, in 251 patients, the relationship between the minimal phototoxic dose (MPD) and a number of variables, including skin type, ingested dose of 8 methoxypsoralen (8-MOP) and history of previous PUVA treatment. The MPD was determined by phototesting 2 h after ingestion of crystalline 8-MOP, given at a standard dose of 0.6 mg/kg (calculated to the nearest 10 mg). No reaction to the highest dose of UVA used for phototesting occurred in 16% of cases; the dose of 8 MOP was significantly associated with non-response. In the patients in whom an erythemal response was obtained, a significant association was found between the MPD and the variables of skin type, ingested dose of 8-MOP, and history of previous PUVA treatment. Thus, by taking these factors into account, a more accurate prediction can be made of an individual patient's erythemal sensitivity to PUVA than relying on skin type alone. That erythemal sensitivity is affected by the ingested dose of 8-MOP (even when all patients received 0.6 mg/kg) suggests that conventional psoralen dosing according to body weight is not ideal. PMID- 8204469 TI - Acquired bullous diseases of childhood: re-evaluation of diagnosis by indirect immunofluorescence examination on 1 M NaCl split skin and immunoblotting. AB - Acquired autoimmune bullous diseases of childhood are rare, and can be difficult to distinguish clinically. We have studied 12 children, with an initial diagnosis of bullous pemphigoid (BP) in eight patients, cicatricial pemphigoid (CP) in one, chronic bullous disease of childhood (CBDC) in one, and epidermolysis bullosa acquisita (EBA) in two. All patients had positive indirect immunofluorescence (IIF) of the BMZ with IgG. Using 1 M NaCl split skin, six patients showed epidermal binding of IgG, with additional IgA in three cases, and in five patients IgG antibodies bound a dermal protein. Immunoblotting studies revealed an antibody to type VII collagen (EBA antigen) in three patients who had a dermal pattern on IIF. Six sera reacted with an epidermal protein of 180 and/or 220 kDa, characteristic of BP and CP. One of the three IgA-positive sera detected 220- and 180-kDa epidermal proteins using anti-IgA antibody. Following these studies the diagnosis was changed in three of the children. The diagnosis of CBDC was changed to either BP or EBA because of the presence of circulating IgG autoantibodies. In two children with an initial diagnosis of BP the diagnosis was changed to EBA. We conclude that the clinical picture in bullous disorders of childhood shows considerable overlap, and is often misleading. Additional circulating IgA autoantibodies seem to be more common in BP than has been recognized previously. Indirect immunofluorescence investigation on 1 M NaCl split skin may be helpful in differentiating between BP and EBA, but does not replace immunoblotting studies. EBA is apparently more common in children than in adults. No difference was found between the children with BP and EBA with regard to the duration of disease. The long-term outlook is good, although the course may be protracted. PMID- 8204470 TI - Epidermolysis bullosa pruriginosa: dystrophic epidermolysis bullosa with distinctive clinicopathological features. AB - We report a study of eight unrelated adult patients with a highly distinctive phenotype of dystrophic epidermolysis bullosa. It is characterized clinically by pruritus, lichenified or nodular prurigo-like lesions, violaceous linear scarring, occasional trauma-induced blistering, excoriations, milia, nail dystrophy and, in some cases, albopapuloid lesions on the trunk. The scarring is most evident on the limbs, particularly on the shins, with relative sparing elsewhere. Intact blisters are rarely seen. Physical signs were present at birth in three patients, but in the others skin manifestations were first noticed between 6 months and 10 years of age. Five cases are sporadic, but three of the eight patients have a history of familial involvement, with autosomal dominant inheritance in two cases and recessive transmission in the other case. Studies of the dermal-epidermal junction showed alterations in the number and ultrastructure of anchoring fibrils in lesional, perilesional and non-lesional skin, consistent with a diagnosis of dominant or localized recessive dystrophic epidermolysis bullosa. These patients represent an unusual, poorly recognized form or expression of dystrophic epidermolysis bullosa which has features in common with a variety of acquired inflammatory dermatoses. PMID- 8204471 TI - Clinical, light and electron microscopic features of recessive congenital ichthyosis type I. AB - Based on electron microscopic features, recessive congenital ichthyoses have recently been divided into four subgroups designated ichthyosis congenita (IC) types I, II, III and IV. Type II is characterized by cholesterol clefts in the horny cells, type III by perinuclear elongated membranes in the granular and horny cells, and type IV by masses of lipid membranes in granular and horny cells. Clear electron microscopic criteria for type I are lacking, although the presence of lipid droplets in the horny cells has been suggested as a criterion. In the present study we included ichthyosis patients with (i) recessive inheritance, (ii) erythrodermic fine scaling, (iii) lack of fine structural markers of IC types II-IV. Patients with ichthyotic syndromes were excluded. The case material consisted of 21 patients from 14 families. Eight were collodion babies at birth, but three were normal. Nine had ectropion, the flexures were affected in 12, and the palms and soles were thickened in all but one patient. On electron microscopy lipid vacuoles in the horny cells were common, but were absent in four patients. Changes in other lipid-related structures, including keratinosomes, were common. We conclude that currently type I can be diagnosed only by excluding the other types of ichthyosis. Clinically, IC type I corresponds to classical non-bullous congenital ichthyosiform erythroderma, but there is marked heterogeneity among affected individuals. PMID- 8204472 TI - Cyclosporin in atopic dermatitis: a multicentre placebo-controlled study. AB - The efficacy of cyclosporin (Sandimmun) given in a daily dose of 5 mg/kg for 6 weeks in severe atopic dermatitis was confirmed in this double-blind, placebo controlled, short-term study. Of the 46 patients included in the study, 23 were randomized to receive cyclosporin and 23 to receive placebo. Four of the 23 patients (17%) on cyclosporin, and 14 of the 23 patients (61%) who received placebo, discontinued the trial because of inefficacy. All patients who discontinued the trial were assessed following the principle of 'intention to treat'. Compared with the baseline, the mean scores for disease severity [6-area, total body severity assessment (TBSA)] improved by 55%, and the mean scores for extent of disease [rule-of-nines area assessment (RoNAA)] improved by 40%, in patients treated with cyclosporin. Nine of the patients who received cyclosporin and completed the study (n = 14) had an individual reduction of disease severity (TBSA) of 75% or more, and in three patients this reduction was nearly 100%. In the placebo group, a mean worsening of disease severity (4%) and of extent of the disease (25%), compared with the baseline, was observed at week 6. Patients' and investigators' mean scores for the overall efficacy were similar, and showed a statistically significant difference in favour of cyclosporin. Two patients on cyclosporin developed hypertension during therapy, and one of these withdrew from the study. At the end of the trial, no statistically significant differences in the systolic or diastolic blood pressures were observed between the two groups. In the cyclosporin group, the increases in the values of serum creatinine and bilirubin at week 6, compared with the respective values at the baseline, were statistically significantly different from those in the placebo group, but all values normalized in the post-treatment period. Cyclosporin can be a safe and very effective treatment in episodes of severe atopic dermatitis, provided that the recommended guidelines for its administration are strictly observed. PMID- 8204473 TI - Increased plasma activity of plasminogen activator inhibitor 1 (PAI-1) in two patients with Klinefelter's syndrome complicated by leg ulcers. AB - Klinefelter's syndrome is the most frequent major abnormality of sexual differentiation in men with two or more X-chromosomes, and affects one in 500 males. The syndrome is characterized by eunuchoid body proportions, scanty facial and body hair, gynaecomastia, and small firm testes. Leg ulcers, especially in combination with hyperpigmentation, have been reported in association with Klinefelter's syndrome. Thromboembolic processes are also frequently observed. The leg ulcers in patients with Klinefelter's syndrome are usually attributed to venous insufficiency. We describe two patients with Klinefelter's syndrome associated with recurrent ulcers and hyperpigmentation on both legs, in whom no venous or other underlying cause could be found. The patients were not taking any drugs, in particular no supplemental androgen therapy. Both had normal plasma testosterone values. We detected increased activity of plasminogen activator inhibitor 1 (PAI-1), with only a partial decrease upon venous occlusion. A possible role for this inhibitor of fibrinolysis in the pathogenesis of ulceration is discussed. PMID- 8204474 TI - Evidence for genetic homogeneity of Setleis' syndrome and focal facial dermal dysplasia. AB - A healthy 14-month-old boy had multiple, circular, scar-like depressions on both temples, which had been present since birth. Delivery had been normal, and had not required the use of forceps or other instruments. His mother and one sister had similar, but less obvious, lesions on the temples. The three affected family members had similar facial features, with laterally deficient eyebrows, and a prominent upper lip with down-turned mouth. Additional features in the baby were sparse lower eyelashes, medial epicanthal folds, and skin dimpling on one side of the chin. Focal facial dermal dysplasia (FFDD) denotes a condition in which there are bitemporal, round, scar-like lesions. It is inherited as an autosomal dominant trait with variable penetrance and expressivity, and there are no associated features. Setleis' syndrome is recessively inherited, and is characterized by similar bitemporal defects associated with other dysmorphic features, including deficient eyelashes and a prominent upper lip. This report of dominantly inherited bitemporal dermal defects with characteristic facies supports the idea that FFDD and Setleis' syndrome are a single disorder. PMID- 8204475 TI - Management and follow-up of harlequin siblings. AB - Harlequin fetus is a rare clinical entity, and survival of affected infants beyond the first year of life is uncommon. Management involves intensive care of the skin and eyes, close monitoring of fluid and electrolyte status, constant support and counselling of parents, and surveillance against infection and side effects of medication. A well-coordinated multidisciplinary approach can prolong survival beyond the neonatal period. We report our experiences in the management and follow-up of two successive harlequin siblings. PMID- 8204476 TI - Invaginated fibrokeratoma with matrix differentiation: a new histological variant of acquired fibrokeratoma. AB - We report two cases of acquired fibrokeratoma which present new clinical and histological features specific to the nail apparatus. There are three histological characteristics. (i) A deep epithelial invagination which develops from the proximal nail fold and is orientated in the same direction as, but is more proximal than, the normal matrix. (ii) The postero-inferior aspect of the cul-de-sac produced by the invagination acts as an accessory matrix, giving rise to a pseudo-nail plate. The granular layer is reduced or absent. (iii) This accessory nail apparatus lies on a conical dermal tumour, sharply demarcated from the surrounding dermis, with a wide base narrowing towards the tip. The finger shaped structure is reminiscent of Kint's type I acquired fibrokeratoma. PMID- 8204477 TI - Pulmonary sarcoidosis presenting as a granulomatous tattoo reaction. AB - A 29-year-old man presented with nodular skin lesions localized to areas of navy blue pigmentation within a tattoo. Light microscopy demonstrated well-defined epithelioid granulomata in close relation to blue and black pigment. Although the patient was asymptomatic, a chest X-ray showed bilateral pulmonary shadowing, and histology of a transbronchial biopsy specimen showed features compatible with a diagnosis of sarcoidosis. X-ray energy dispersive spectroscopy identified copper and titanium in the tattoo pigment. These elements were not found in tissue from the lung biopsy. The cutaneous eruption resolved with oral steroid therapy. Our observations suggest that the granulomatous reaction in the tattoo was a manifestation of sarcoidosis, rather than a specific reaction to pigment. PMID- 8204478 TI - Penile melanosis successfully treated with the Q-switched ruby laser. AB - Penile melanosis is an uncommon benign primary pigmentary disorder affecting the penile shaft and/or glans. We report the successful treatment of penile melanosis using the Q-switched ruby laser. PMID- 8204479 TI - Bacillary angiomatosis in a patient with lymphocytic leukaemia. AB - A 78-year-old man, who suffered from chronic lymphocytic leukaemia and diabetes mellitus, but was human immunodeficiency virus (HIV)-negative, developed disseminated angiomatous papules following a cat scratch. Bacillary angiomatosis was diagnosed by light and electron microscopic demonstration of the causative bacteria in the vascular lesions. The lesions resolved completely when he was treated with erythromycin. This case demonstrates that bacillary angiomatosis can be an important cutaneous manifestation of immunodeficiency in individuals who are not infected with the human immunodeficiency virus. PMID- 8204480 TI - A fatal case of scleredema of Buschke. AB - Scleredema of Buschke is a rare disorder characterized by the development of areas of skin induration which usually resolve spontaneously. It is occasionally associated with a benign gammopathy, and rarely with myelomatosis. We describe a 60-year-old woman with extensive skin changes, who developed IgA myeloma. Unusually, her skin disease did not respond to conventional myeloma therapy. Death occurred as a consequence of the progressive skin disease. PMID- 8204482 TI - Safety and efficacy of longer-term lower-dose cyclosporin A therapy. PMID- 8204481 TI - An association between psoriasis and hereditary multiple exostoses. A clue for the mapping of a psoriasis susceptibility gene? AB - Chronic plaque psoriasis affects approximately 1.6% of the U.K. population. Population, family and twin studies all strongly suggest an important genetic component in the pathogenesis of the disease, although genetic linkage studies have, so far, failed to identify susceptibility genes. We describe a family in which psoriasis cosegregates through three generations with a known autosomal dominant disorder, hereditary multiple exostoses (HME). A major locus for HME has recently been mapped to chromosome 8q. Observations in this family may provide a mapping clue for a psoriasis susceptibility gene. PMID- 8204483 TI - Severe oropharyngeal deglutition abnormalities in a patient with systemic sclerosis, managed with a gastrostomy. PMID- 8204484 TI - Trichophyton tonsurans kerion in an elderly woman. PMID- 8204485 TI - Intralesional interferon alpha-2b has no effect in the treatment of keloids. PMID- 8204486 TI - Neonatal retention of type VII collagen, transient bullous dermolysis of the newborn and recessive epidermolysis bullosa dystrophica inversa. PMID- 8204487 TI - Elevated levels of epidermal growth factor in a patient with tripe palms. PMID- 8204488 TI - Hydroxyurea-induced lupus erythematosus. PMID- 8204489 TI - Toxic epidermal necrolysis. Treatment with pentoxifylline. PMID- 8204490 TI - Colloid cysts in children. AB - Three patients with colloid cysts were identified among approximately 1,400 patients with brain tumors seen at the Hospital for Sick Children in Toronto between 1952 and 1992. These and 34 previously published cases of colloid cysts in children were reviewed. Colloid cysts are rare causes of headaches and papilloedema in children. They usually present with chronic headaches and increased intracranial pressure. Although acute deterioration can occur at any time, it is uncommon. A CT scan or MRI with intravenous contrast is necessary to identify them, particularly those which are isodense. The growth, and subsequent postoperative recurrence of a colloid cyst in 1 youth argues for treatment by complete surgical excision in children. PMID- 8204491 TI - A search for gli expression in tumors of the central nervous system. AB - The gli gene was originally isolated from DNA amplified in double minutes in a glioblastoma (D259MG). Using a sensitive RNA-RNA hybridization, we tested a series of central nervous system tumors for expression of the gli gene. These included 8 glioblastoma cell lines, plus cell cultures of 5 glioblastomas, 4 anaplastic astrocytomas, 3 different ependymal tumors, a malignant meningioma, and a medulloblastoma. Two normal glial cell cultures were also examined. There was no gli expression in any of these specimens. In glioblastoma D259MG, approximately 130 molecules of gli mRNA per cell were present and the half-life of the mRNA was approximately 5 h. By reverse transcription and PCR, gli mRNA was observed in 4 cell lines and in normal human glial cells, but the level was estimated to be less than one five hundredth of that in the D259MG cell line. The results suggest that gli expression in central nervous system tumors is a rare event and mostly likely associated with amplification of the gene. PMID- 8204492 TI - Pediatric head injury: a further experience. AB - This report consists of 201 patients seen at the Medical College of Virginia from May 1976 to October 1991. They are divided into two groups. The first group is from May 1976 to June 1984 and the second group is from July 1984 to October 1991. The two groups are compared as regards age, Glasgow coma score (GCS), presence of surgical mass lesion, mechanism of injury, intracranial pressure (ICP) course, and outcome. There was a significant difference in the initial GCS between the first and second group with the second group having a lower GCS. In addition, an analysis of the ICP course in group II showed a much lower incidence (5%) of a normal ICP course. There was no difference in outcome between the two groups. The results in the 201 patients are compared to other series. PMID- 8204493 TI - Spinal cord compression in homozygous beta-thalassemia intermedia. AB - Symptomatic spinal cord compression caused by an epidural mass of extramedullary hematopoietic tissue in patients with beta-thalassemia is a rare occurrence, that becomes exceptional in childhood and adolescence. The literature is not uniform about the optimal treatment of these patients and different modes of therapy have been proposed so far, including surgical excision or decompressing laminectomy followed by local irradiation and/or hypertransfusional regimens. We report the successful treatment of such a complication in an adolescent with homozygous beta thalassemia by surgery followed by repeated blood transfusions aimed at maintaining hematocrit at normal levels. PMID- 8204494 TI - Treatment of intraventricular hemorrhage in the premature infant with urokinase. A preliminary report. AB - Hydrocephalus secondary to intraventricular hemorrhage in the premature infant is common and is secondary to the presence of blood in the subarachnoid space. Rapid clearance of the blood may reduce the incidence of permanent hydrocephalus and mitigate the need for shunt placement. We have treated 4 premature infants with posthemorrhagic hydrocephalus with urokinase, a thrombolytic agent, instilled into the ventricles via a surgically paced ventricular access device. The infants were treated with 10,000 IU of urokinase twice a day for 1 week. No adverse reactions have occurred and none of the infants has required shunt placement. In a group of historical controls, the shunt rate was 87%. PMID- 8204495 TI - Epidural pain management in the postrhizotomy patient. AB - The authors report a randomized double-blind prospective study comparing epidural morphine 80 micrograms/kg to epidural morphine 80 micrograms/kg plus butorphanol 40 micrograms/kg in children undergoing rhizotomy. Up to 50% of children receiving epidural morphine alone will experience side effects of nausea, vomiting, pruritus, urinary retention or respiratory depression. The addition of the narcotic agonist-antagonist butorphanol virtually eliminated these side effects without compromising analgesia or causing undue sedation. Parent satisfaction was greater than 90%. PMID- 8204496 TI - The use of motor evoked potentials in the diagnosis of psychogenic quadriparesis. A case study. AB - We present a case illustrating the usefulness of motor evoked potentials (MEPs) in differentiating psychogenic from organic postoperative paralysis. Discussed is a 12-year-old girl who underwent surgery for the repair of a recurrent syringomyelia. On the 6 day after a proximal revision of her syringoperitoneal shunt she returned to the hospital with deep quadriparesis, bowel and bladder incontinence, and complaining of severe headache. An MRI scan showed the syrinx to be collapsed, and removal of the shunt had no impact on her clinical symptoms. Repeat somatosensory evoked potentials (SEPs) showed no change in comparison to those obtained at the end of her preceding surgery. MEPs were normal for the lower extremities, a finding which is inconsistent with a severe upper motor neuron lesion. She was diagnosed with psychogenic paralysis, and fully recovered within 1 month. We propose that a neurophysiological evaluation including MEPs is useful in the differential diagnosis of psychogenic and organic motor weakness. PMID- 8204497 TI - Meningeal tumors in children. 1983. PMID- 8204498 TI - Cerebral syrinx with Chiari I malformation. AB - A 13-year-old female presented with acute left gaze paralysis. MRI revealed hydrosyringomyelia (HSM) with syringobulbia in the left pons extending cephalad into the centrum semiovale. A suboccipital craniotomy was performed and the foramen of Magendie was imperforate. Ocular movements normalized in 2 months and postoperative MRI confirmed resolution of the cerebral syrinx and syringobulbia and diminished HSM. This case represents an extreme example of the altered spinal fluid dynamics with Chiari I malformation. Theories on HSM are reviewed. PMID- 8204499 TI - Sacral agenesis associated with spinal cord syrinx. AB - The antemortem diagnosis of syringomyelia in the setting of sacral agenesis has not been reported before. We describe the clinical and neuroimaging features in 3 patients. None has required surgical intervention to date. PMID- 8204500 TI - Pharmacology of interleukin-1 actions in the brain. PMID- 8204501 TI - Immune modulating therapies for idiopathic inflammatory bowel diseases. PMID- 8204502 TI - Interleukin-1. PMID- 8204503 TI - Endogenous cardiac glycosides. PMID- 8204504 TI - Antisense catalytic RNAs as therapeutic agents. PMID- 8204505 TI - Gene-mimetic substances: drugs designed to intervene in gene expression. PMID- 8204506 TI - Progress toward understanding the cannabinoid receptor and its second messenger systems. PMID- 8204507 TI - HIV protease as an inhibitor target for the treatment of AIDS. PMID- 8204508 TI - Modulation of cytokine function: therapeutic applications. PMID- 8204509 TI - Management of lymphoma in the 1990s: introduction to the proceedings of the Fifth International Conference on Malignant Lymphoma. PMID- 8204510 TI - Hodgkin's disease in children: combined modality treatment for stages IA, IB, and IIA. Results in 356 patients of the German/Austrian Pediatric Study Group. AB - 356 children below 16 yrs of age with CS/PS IA, IB, and IIA were treated in the studies HD-78, HD-82, HD-85, HD-87, and OEPA-pilot 87 between June 1978 and Sept 1990. All patients received combined modality treatment (CMT) with 2 courses of chemotherapy (CT). In HD-78 and HD-82, the MOPP-derived drug combination OPPA (ADR instead of mechlorethamine) was applied. Extended-field radiotherapy (RT) was given in HD-78 using 36-40 Gy to involved-fields (IF) and 36-40 Gy vs. 18-20 Gy to adjacent fields. In HD-82 only IF-RT was applied using 35 Gy. When gonadotoxic effects of procarbazine (PC) in boys was detected in follow-up examinations, this drug was eliminated in studies HD-85 and HD-87 (OPA). Dosages of IF-RT were 35 Gy in HD-85 and 30 Gy in HD-87. With HD-87 a simultaneous pilot study was initiated to test the new combination OEPA (E = etoposide) together with 25 Gy IF-RT. RESULTS: (May 1993): Rates for event-free survival and survival are HD-78 (73 patients): 0.90 and 0.97 at 10 yrs; HD-82 (100 patients): 0.98 and 1.0 at 10 yrs; HD-85 (53 patients): 0.85 and 0.98 at 8 yrs; HD-87 (104 patients): 0.85 and 0.99 at 6 yrs; OEPA-pilot (26 patients): 0.96 and 0.96 at 5 yrs. No secondary leukemias, MDS, or solid tumors were observed in 14-yr observation time. After 2 OPPA, elevated FSH levels indicating impaired spermatogenesis were found in 29% of male patients. In contrast, after 2 OPA (without PC) only normal FSH levels were observed. In female patients, no gonadal dysfunction was found. Subclinical hypothyroidism was seen only after RT doses of > 30 Gy to the neck. Cardiomyopathies were not observed. CONCLUSION: 2 OPPA plus IF-RT using < 30 Gy can presently be considered optimal therapy for girls with localized HD. 2 OEPA plus 25 Gy IF-RT are being evaluated for boys in a phase III study (HD-90). In summary, there are good reasons to use CMT in early stages of HD in children, provided a highly effective CT of short duration and low long-term toxicity with low-dose IFI is applied. PMID- 8204511 TI - Hybrid LOPP/EVA is not better than LOPP alternating with EVAP: a prematurely terminated British National Lymphoma Investigation randomized trial. AB - In a British National Lymphoma Investigation (BNLI) trial, patients with advanced Hodgkin's disease (stages IB, IIB, III, and IV) were randomized between initial treatment with a LOPP alternating with EVAP regimen and a LOPP/EVA hybrid regimen. The two regimens contained identical drug dosages and varied only in their scheduling. The complete remission (CR) rate in the hybrid regimen was significantly less than that in the alternating regimen, and the trial was terminated after approximately 18 months since there appeared to be no chance of the hybrid regimen ever proving superior to the alternating regimen. A total of 160 patients were entered into the trial before recruitment was terminated, 86 being randomized to the alternating regimen and 83 to the hybrid regimen. The CR rates for the alternating and hybrid arms were 65% and 40%, respectively (p < 0.002). The CR relapse-free survivals at 2 years in these two arms were 85% and 79%, respectively (p = 0.7); the overall disease-free survivals at 2 years were 57% and 32%; and the overall survivals at 2 years were 88% and 78% (p = 0.5). This trial emphasizes the impact of drug scheduling, which should be taken into account in the design of future hybrid regimens. PMID- 8204512 TI - Critical review of the role of hemopoietic growth factors in dose intensification and outcome in the treatment of non-Hodgkin's lymphoma. PMID- 8204513 TI - Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for follicular lymphoma. AB - Since June 1985, 121 patients with follicular lymphoma aged 24-61 years (median 43) have received myeloablative therapy (cyclophosphamide: 60 mg/kg x 2, + total body irradiation: 200 cGy x 6) with autologous bone marrow transplantation (CY+TBI+ABMT) as consolidation of 2nd or subsequent remission. The marrow mononuclear cell fraction was treated in vitro with anti-CD20 alone and baby rabbit complement at St. Bartholomew's Hospital (SBH) and with the addition of anti-B5 and anti-CD10 at the Dana Farber Cancer Institute (DFCI) prior to reinfusion. There were 4 treatment related deaths, (nonengraftment 1, haemorrhage 1, systemic fungal infection 1, veno-occlusive disease 1). The median time for neutrophil recovery (> 0.5 x 10(9)/1) was 26 days (range 10 to 59 days), and for platelets (> 20 x 10(9)/1), 30 days (range 12 to 73 days). One patient did not engraft and 7 have had delayed recovery of red cells and platelets (> 3 months). Two other patients have subsequently developed acute myelogenous leukaemia and 5, evidence of myelodyplasia. Seventy-one patients continue in unmaintained remission between 3 months and 7 years, with a median follow up of 2.5 years. Forty-three have developed recurrent lymphoma; 98 remain alive. Freedom from progression was the same, irrespective of whether patients received CY + TBI + ABMT whilst in a complete or partial remission and did not depend on the specific remission in which treatment was given (2nd: 90 patients vs. > 2nd: 31 patients).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204514 TI - Autologous bone marrow transplantation for low-grade non-Hodgkin's lymphoma: the European Bone Marrow Transplant Group experience. EBMT Working Party for Lymphoma. AB - BACKGROUND: Influenced by successful results treating intermediate- and high grade non-Hodgkin's lymphoma (NHL), high-dose therapy followed by autologous bone marrow transplantation (ABMT) is increasingly applied in low-grade NHL. However, the published data are limited. PATIENTS AND METHODS: In the European Bone Marrow Transplant Group (EBMT) Registry 92 patients with low-grade NHL treated with ABMT could be identified. RESULTS: The overall progression-free survival was 52% at 5 years with a median follow-up of 19 months. Patients with a complete remission or responsive disease at ABMT had a better outcome. There was no benefit for patients transplanted with either total body irradiation in the conditioning regimen or a purged autograft. CONCLUSIONS: Although the median follow-up is short, the data are very promising and warrant a randomized trial analyzing the value of high-dose therapy and purging in low-grade NHL. PMID- 8204515 TI - Early bone marrow transplantation in Hodgkin's disease. AB - Bone marrow transplantation can be curative for patients with advanced Hodgkin's disease. Results are better when patients are transplanted after only one chemotherapy regimen at a time of minimal disease. Clinical trials are beginning testing bone marrow transplantation as part of the initial treatment for patients with widely disseminated, poor prognosis Hodgkin's disease. PMID- 8204516 TI - The treatment of Hodgkin's disease. PMID- 8204517 TI - Lymphoma complicating immunodeficiency disorders. AB - BACKGROUND: An increased incidence of lymphoma is seen in various types of immune deficiency or dysregulation, including congenital immune deficiency diseases, organ transplantation with iatrogenic immunosuppression, autoimmune disorders, endemic Burkitt's lymphoma, and AIDS-associated lymphoma. RESULTS: The lymphomas seen in various immunodeficiency disorders share certain features. Thus, all consist of high-grade, B-cell tumors, with predilection for extranodal involvement, and short survival. However, certain biologic and clinical differences are also apparent. Thus, while the transplantation-associated lymphomas are uniformly associated with the Epstein-Barr Virus (EBV), this association is not seen in all systemic AIDS-related lymphomas, nor in all congenital immune deficiency disorders. Likewise, while c-myc activation has been described in certain types of HIV-related lymphomas, c-myc dysregulation has not been reported in association with organ transplantation. CONCLUSIONS: The study of lymphomatous disease in various states of immune dysregulation may allow an understanding of the diverse pathogenic mechanisms operative in the development of malignant lymphoma in man. PMID- 8204518 TI - Hodgkin's disease in patients with HIV infection and in the general population: comparison of clinicopathological features and survival. AB - BACKGROUND: Hodgkin's disease (HD) has been described in patients with HIV infection in association with unfavourable prognostic factors. Similarly, HD in the older general population has a poorer prognosis than in younger patients. PATIENTS AND METHODS: With the aim of comparing the clinicopathological features and survival of HD in HIV-infected patients and in the general population, we analysed 176 patients with HD from 1986 to 1992. We divided the 84 HIV-negative patients into two groups: group A included patients less than 55 years old, group B patients of 55 years or older. This division was made in order to compare HD in HIV-infected patients with the less favourable group of patients with HD in the general population, i.e., older patients. RESULTS: Patients of the older group and HIV-infected patients had a significantly lower frequency (31% and 21%, respectively) of nodular sclerosis subtype compared to the younger group (85%). Mixed cellularity (MC) is significantly more frequent both in the older group and in HIV-infected patients. Lymphocyte predominance is more frequent (16%) in older patients than in the other two groups. HIV-infected patients are more likely to show advanced stages, B symptoms, and extranodal involvement. Chemotherapy (CT) alone has been the most widely used (83%) treatment in HIV-infected patients, while CT plus radiotherapy (RT) has been mostly employed in the general population. Twelve (14%) HIV-infected patients did not receive any treatment. Complete remission was achieved in 51% of the cases in the HIV-infected patients, and around 90% of the cases in the general population. The estimated 4-year survival rate in the HIV-infected patients is much lower (33%) than in the other two groups (100% in group A, and 88% in group B). CONCLUSION: While MC is the most common histological subtype both in HIV-infected patients and in the older general population, HD in HIV-infected patients has a worse prognosis than in the older general population, not only because of underlying HIV infection, but also because of the more unfavourable clinicopathological features at presentation. PMID- 8204519 TI - Stage, serum LDH, and performance status predict disease progression and survival in HIV-associated lymphomas. AB - PURPOSE: This is a review of treatment of 44 patients with positive HIV serology (positive HIV) and lymphoma. MATERIALS AND METHODS: Twenty patients had diffuse large-cell lymphoma (DLCL), and 18 had small noncleaved-cell lymphoma (SNCCL). Three had Hodgkin's disease (HD) and 3 had diffuse small- or mixed-cell lymphoma. These patients received intensive chemotherapy regimens for management of their disease; most were regimens in use at our institution for patients with lymphoma who did not have positive HIV. RESULTS: The complete response to treatment (CR) was 77% for all patient, 80% for those with DLCL, and 72% for those with SNCCL. Stage, serum LDH, and performance status were predictors of complete remission and freedom from progression. Though there was a tendency for patients with a T4 cell count of < or = 200 to have a higher risk of opportunistic infections while receiving therapy, most infections were controllable with appropriate antibiotic management. More than one-half of the deaths in this study occurred after completion of therapy in complete remission, with a median survival of only 11 months, and were attributable to AIDS-related complications. CONCLUSIONS: Our data suggest that (1) patients with lymphoma who have positive HIV have responses to chemotherapy similar to those expected for patients who are HIV-negative; (2) most infectious complications are manageable with appropriate therapy during treatment; and (3) after completion of chemotherapy, treatment should focus on control of progression of AIDS-related complications. PMID- 8204520 TI - Modern treatment of malignant lymphomas: a multidisciplinary approach? The Kaplan Memorial Lecture. AB - The aim of this review is to examine critically, in Hodgkin's disease and in non Hodgkin's lymphomas, (a) whether combined modality treatment is superior to optimal radiotherapy or chemotherapy alone in most stages of the disease; (b) whether its indications could be further expanded by the use of new drug regimens and newer radiation techniques that can now substantially reduce the risk of long term iatrogenic morbidity; and (c) whether it may become a necessary approach in the future because staging laparotomy and even lymphangiography are progressively falling into disuse. In conclusion, for the next decade or so, I do not foresee a departure from complex treatment programs. Although fewer patients are being referred to major research centers, the treatment of malignant lymphomas is not ready as yet to be relegated to the care of the single physician in a private office or local hospital. PMID- 8204521 TI - The gallium scan predicts relapse in patients with Hodgkin's disease treated with combined modality therapy. AB - The gallium scan (GS) is an important indicator of disease activity in untreated Hodgkin's disease, especially in the upper torso, and may be an important predictor of results for patients who have completed chemotherapy and radiotherapy (XRT). To better define the importance of the GS in predicting treatment results in a group of patients treated with uniform therapy, we performed GS prior to treatment in 46 patients with pathologically or clinically staged I-III Hodgkin's disease who received three cycles of NOVP (Novantrone, vincristine, vinblastine, prednisone) followed by XRT. Staging methods included computerized tomography (CT) of the chest, abdomen, and pelvis, lymphangiogram, and the GS, using 8 to 10 millicuries with single photon emission computed tomography (SPECT) of the upper and lower torso. Only 3 patients had negative GS before chemotherapy. After three cycles of NOVP and prior to XRT, the other 43 had repeat GS performed. Complete remission (CR) was judged by disappearance of disease after all therapy without considering GS results. The CR for those with initial positive GS was 93%. The three-year freedom from progression result for stage I-II was 94%, and the three-year overall survival was 96%; corresponding results for stage III were 86% and 100%, respectively. None of the prognostic factors for analysis, including bulky adenopathy, hilar involvement, or B symptoms, was an important predictor of results. However, only 1 of the 33 with a negative GS after these NOVP has had progressive disease compared to 3 of the 10 with a GS that remained positive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204522 TI - Late mortality in young BNLI patients cured of Hodgkin's disease. AB - A retrospective analysis was made of 1057 young patients (aged 15-29) with Hodgkin's disease (HD) who were entered into British National Lymphoma Investigation (BNLI) trials and studies between 1970 and 1992, and who had attained complete remission and remained disease-free thereafter from either their first-line (n = 774) or second-line (n = 283) treatment. Overall survivals at 20 years for those remaining disease-free from first-line and second-line treatment were 93% and 84%, respectively, compared to a survival of approximately 98.5% in the general population. In young patients cured by modern first-line therapeutic techniques, long-term survival should in future be only a little below that expected in the general population, and the emphasis of future trials should be directed towards the improvement of the efficacy of first-line treatment. PMID- 8204523 TI - Fludarabine--present status and future developments in chronic lymphocytic leukemia and lymphoma. AB - BACKGROUND: Fludarabine monophosphate (fludarabine) is an adenine nucleoside analogue active in indolent lymphoproliferative diseases which has an increasing role in studies incorporating combinations of agents which exploit biochemical modulation, inhibition of DNA repair, and radiosensitizing effects. PATIENTS AND METHODS: Patients with lymphoma and chronic lymphocytic leukemia (CLL) treated at the M. D. Anderson Cancer Center (MDACC) and reports in the literature form the basis of this report. RESULTS: CLL has traditionally been treated with alkylating agents and corticosteroids. In this study, fludarabine has shown marked cytoreductive ability in both previously treated patients and untreated patients. In the former group, there has been a 55% response rate in 374 patients, and 79% in the untreated CLL group. Fludarabine has also been very active in the management of low-grade lymphomas, with two-thirds of patients with follicular lymphoma and half of those with other indolent lymphomas responding. Waldenstrom's macroglobulinemia is also sensitive to the effects of fludarabine. Combination regimens were developed incorporating the substantial effectiveness of fludarabine and mitoxantrone where in the previously treated low-grade lymphoma group 25 of 28 patients (89%) responded. Fludarabine has the effect of increasing the triphosphate form of cytosine arabinoside in acute and chronic leukemic cells. This modulation has now been translated into therapy for acute leukemia and combined with cisplatinum in refractory CLL. Fludarabine inhibits DNA repair and enhances cross-linking of DNA by cisplatinum. The combination of fludarabine, ara-C, and cis-platinum is now being used in refractory CLL. Fludarabine is a radiation sensitizer, inhibiting repair of DNA damage. Studies are ongoing with this combination. CONCLUSIONS: Fludarabine is a potent molecule with a wide range of biochemical effects. Optimal use of this drug alone and in combination is continuing to be explored. PMID- 8204524 TI - Surgery of squamous cell carcinoma of the esophagus. AB - Identification of prognostic factors which may influence survival in patients with squamous cell carcinoma of the esophagus is critical for the selection of those patients who benefit from a surgical resection and the choice of the radicality of the procedure. We evaluated the tumor characteristics which independently influenced survival in 249 consecutive patients with squamous cell carcinoma of the esophagus who had undergone en bloc resection and 2-field lymphadenectomy. Multivariate analysis in the entire patient population identified (1) the pT category, (2) the pN category, (3) more than 7 positive mediastinal lymph nodes, and (4) the presence of residual tumor after resection, i.e. a R1 or R2 resection, as the only independent factors influencing survival time. In a second multivariate analysis of 94 patients who survived the procedure for at least 30 days, who had a R0 resection, and who did not have preoperative neoadjuvant therapy, only the pN-category, the presence of more than 7 positive mediastinal lymph nodes, and the ratio between positive and removed mediastinal lymph nodes independently influenced survival. These data suggest that only a R0 resection, i.e. complete macroscopic and microscopic tumor removal, can increase survival in patients with squamous cell carcinoma of the esophagus. In patients with a limited number of positive mediastinal lymph nodes the prognosis may be improved by a 2-field lymphadenectomy, if the number of removed mediastinal lymph nodes exceeds the number of positive nodes by a factor of at least 5. PMID- 8204525 TI - Perioperative radiotherapy +/- chemotherapy in rectal cancer. AB - Locoregional failure which occurs in 25%-50% of patients with rectal cancer undergoing potentially curative surgery, can be significantly reduced by either postoperative adjuvant irradiation and also by preoperative radiotherapy. In view of the possible local side effects/complications, optimal irradiation techniques including accelerator and 3-4 field techniques are mandatory. Combined treatment consisting of radiotherapy plus chemotherapy appears to be more efficient than pelvic irradiation alone. It seems that reductions in the rate of pelvic and extrapelvic tumor recurrences which are not dramatic but of clinical significance are followed by an improved survival. The 1990 Consensus conference of the National Institute of Health recommended combined postoperative radiotherapy and chemotherapy for patients with T3N0, T4N0 and any TN1-3 rectal cancer. For future trials, the main goal has to be optimization of radiotherapy plus chemotherapy in the perioperative treatment of rectal cancer. The most important unanswered question is whether the highest therapeutic ratio is obtained by pre- or postoperative treatment. PMID- 8204526 TI - Colorectal carcinoma: current problems and future perspectives. AB - Colorectal carcinoma represents a highly interesting model for the biological development of a solid tumor, the efficacy or primary and secondary prevention and the development of chemotherapeutic and immunologic strategies for adjuvant and/or neoadjuvant treatment is resectable stages. Adjuvant systemic 5 FU/levamisole is currently the standard adjuvant treatment for stage III colon cancer. 5-FU/folinic acid for 6 months seems to achieve equivalent results. Continuous infusion of 5-FU for 7 days postoperatively via the portal vein achieves also a comparable improvement in disease-free and overall survival. Beyond the long term systemic as well as short time intraportal chemotherapy, adjuvant immunotherapy with either 17-1A murine monoclonal antibody or autologous tumor vaccine achieves quite comparable results like adjuvant chemotherapy. Therefore the combination of these modalities might be of high interest for further investigation. The current EORTC study for colorectal cancer investigates the role of the combination of short time regional and long term systemic chemotherapy. For rectal cancer stage II and III adjuvant 5-FU plus radiation is currently the standard. However, further improvement seems possible with 5-FU given as continuous infusion during radiation; this approach is currently investigated in an ongoing Intergroup study. A further attractive approach, particularly for locally advanced, borderline resectable rectal cancer is the neoadjuvant combined modality treatment with 5-FU/folinic acid plus radiation followed by surgery and further adjuvant chemotherapy; this neoadjuvant treatment is currently being investigated in comparison to postoperative 5-FU/folinic acid plus radiation in an ongoing Intergroup study. Future protocols should also include immunotherapy with 17-1A antibody which significantly prolongs disease free and overall survival also in rectal cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204527 TI - Neoadjuvant therapy for squamous cell esophageal carcinoma. AB - A number of studies have demonstrated that preoperative chemotherapy (CTx) and combination radiochemotherapy (RTx/CTx) in patients with potentially resectable and locally advanced squamous cell esophageal carcinoma is feasible. In patients with potentially resectable tumors, neoadjuvant therapy followed by surgical resection has, however, so far not shown an increase in the resection rate, rate of complete macroscopic and microscopic tumor resections, i.e. R0-resections according to the UICC, or survival time as compared to patients who had surgical resection alone. In this situation a survival benefit, if at all, can be expected only in those who respond to preoperative therapy. At the present time preoperative CTx or RTx/CTx in patients with potentially resectable esophageal carcinoma must therefore be considered investigational and should not be performed outside the context of clinical trials. In patients with locally advanced esophageal carcinoma, neoadjuvant therapy markedly increases the rate of R0-resections and appears to prolong survival. Combined modality therapy in this context is, however, associated with a substantial perioperative mortality and morbidity. Open questions that have to be addressed by randomized studies include the role, extent and timing of surgical resection in the combined modality approach to patients with locally advanced squamous cell esophageal carcinoma. Research has to focus on preoperative staging modalities and the development of more effective and less toxic preoperative therapy regimen to improve identification of patients that might benefit from combined modality therapy and to more effectively combat systemic recurrences. PMID- 8204528 TI - Current status and future directions in the treatment of localized esophageal cancer. AB - Due to insufficient local tumor control in the majority of esophageal carcinoma (EC) patients and due to distant recurrences, the dismal prognosis of patients with EC has not essentially changed during the past two decades. This holds true despite extended surgical procedures and improved radiation techniques. The 2 year survival rates in stage IIB/III which represent two-thirds of the patients with localized EC is still less than 20%. Therefore, clinical efforts in the management of EC focus on combined modality treatment (CTM), usually preoperative chemotherapy (CTx)/chemoradiotherapy (CTx/RTx) or CTx/RTx alone. Up to now, results of CTM in potentially resectable EC have not shown that preoperative CTx or CTx/RTx is superior to surgery alone with respect to resectability, local tumor control and overall survival. However, CTx responders who subsequently underwent a complete tumor resection had a markedly improved long term survival indicating that the inclusion of CTx in the treatment of EC may improve the prognosis. The benefit of CTx could also be demonstrated in a randomized trial comparing RTx alone versus CTx/RTx with a reduction of local and distant failures and significantly improved survival in the CTM arm. Similar observations were made with CTM in locally advanced disease. To date, there is sufficient evidence that preoperative treatment of EC may improve prognosis at least of subgroups of patients with this tumor. However, this has to be confirmed in well designed (proper staging including endoscopic ultrasound, etc.) randomized trials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204529 TI - Strategies in the surgical treatment of gastric carcinoma. AB - Surgical therapy still represents the treatment of choice for patients with primary gastric adenocarcinoma, but surgery may have reached its limits concerning the rate of resectability, postoperative mortality and survival rates. Resectability is as high as 80%, mortality after resection ranges between 3% and 5% and the best survival data can be achieved if potentially curative tumor-free (R0-) resection including systematic lymphadenectomy can be performed. Significant prognostic benefits are to be expected in tumor stages II and IIIA. Most gastric carcinomas, however, are diagnosed in far advanced tumor stages (i.e., stage IIIB and IV) and the survival rates in these patients remain disappointing. Multimodality treatment, consisting of preoperative chemotherapy and surgery, may be an encouraging alternative strategy. By endoscopic ultrasonography and staging laparoscopy it may be possible to identify patients with locally advanced tumors, so that these patients should be subjected to multimodal therapy to improve their prognosis. Primary surgical treatment should be exclusively performed in patients with tumor stages up to IIIA and those who are not eligable for aggressive chemotherapeutic regimens, while the concept of multimodality therapy needs to be investigated in the other cases within controlled prospective clinical trials. PMID- 8204530 TI - Adjuvant therapy of gastric cancer: have we made any progress? AB - Up to now, the majority of adjuvant chemotherapy trials in gastric cancer have failed to show a clear survival benefit as compared to surgical controls, and this is especially true for trials conducted in western countries. But this does not necessarily mean, that adjuvant chemotherapy of gastric cancer is in general ineffective. There are several common threads that appear repeatedly in adjuvant therapy trials which might help to explain the current situation. In most trials stratification was done according to stage and not to the TNM category leading to important stratification bias. A homogeneous surgical approach and a surgical and pathological quality control was not mandatory. There are sufficient data, that in comparison to 'limited' surgery, extended surgery with systematic lymphadenectomy of the N2 compartment markedly improves the prognosis of patients with stage II and IIIa tumors. The kind of chemotherapy, its timing and scheduling, and route of administration might also have been inappropriate to demonstrate a possible benefit of adjuvant therapy. All these things have to be considered seriously in future well designed trials, if an assumed therapeutic gain is to be demonstrated by adjuvant treatment of gastric cancer. PMID- 8204531 TI - Preoperative chemotherapy of locally advanced gastric cancer. AB - Gastric adenocarcinomas, even in the absence of distant metastases, have a poor prognosis which is particularly dismal when tumors are located in the cardia, in the event of locoregional lymph node involvement and/or bulky tumors. Postoperative adjuvant chemotherapy has never clearly demonstrated its efficacy on survival. Besides ongoing trials using new and more active regimens, preoperative chemotherapy has been used for unresectable cancer due to loco regional extension and when locally advanced cancer is potentially resectable but with poor prognosis such as bulkiness, when tumors are located in the cardia and when there is tumor in the coeliac area at CAT-scan with suspected metastatic lymph nodes. In case of unresectable tumor at initial surgery five publications have reported the ability of chemotherapy to reduce the tumor volume and to allow subsequent resection of the gastric tumor in 40% to 60% of the cases. In these cases there is a clear survival advantage as the median survival reported in 2 of these studies was 12 and 18 months compared to the 4 to 6 months median survival reported in historical studies in case of unresectable cancer [17, 18]. In case of locally advanced gastric tumors some Japanese case reports have demonstrated the ability of preoperative chemotherapy to concentrate in the tumor tissue and to downstage the tumors. Four North American and European studies have demonstrated that preoperative chemotherapy is feasible, and will probably increase the resection rate. J. Ajani has reported 2 studies in which tolerance was acceptable: a major response (R) observed in 24% and 31%, the resectability rates were 72% and 77% and the median survival 15 and 16 months, respectively. Our experience is based on 30 patients treated with a combination of continuous i.v. 5-FU and CDDP. Fifteen had a tumor of the cardia, 15/30 had enlarged lymph nodes and 7/30 a linitis plastica (diffuse type). After a mean number of 3 cycles, 27/30 patients were evaluable for response. One patient achieved a CR and 14 a PR (OR rate 56%, 95% CI: 38% to 74%) but only one of those with linitis plastica responded. Twenty-eight patients underwent surgery and 23 had a macroscopically complete resection (82%). Resectability rate was higher after OR (13/15) than in nonresponding patients (4/12). Toxicity was acceptable, however grade 4 leucopenia in 5 patients and one toxicity-related death were observed. There was no increase in postoperative complications. Nine patients received postoperative chemotherapy and 3 patients with positive margins received postoperative external radiotherapy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8204532 TI - Current status and future directions in the treatment of localized gastric cancer. AB - Although extended surgery plus systematic lymphadenectomy may improve the prognosis of patients with stage II/IIIa (UICC classification) tumors, there is no doubt, that the results of surgery of gastric cancer have reached a plateau. An improvement of the current situation can be expected at best by additional treatment modalities in order to reduce local recurrences and distant metastases. For locally advanced gastric cancer (LAGC), which includes approximately two thirds of patients with locoregionally confined tumors, preoperative chemotherapy represents a promising approach. In surgically or clinically staged inoperable LAGC, approximately half of the patients underwent complete (R0) resection after downstaging induced by active modern chemotherapy. The long-term survival of these patients appears to be about 20%. Well designed randomized studies, however, comparing surgery alone versus preoperative chemotherapy, should be undertaken in LAGC. In view of the high local recurrence rate being observed in published preoperative chemotherapy trials, the inclusion of radiotherapy (intraoperative radiotherapy, simultaneous chemoradiotherapy) or intraperitoneal chemotherapy should be considered for future investigations. In more early stages, curatively resected, adjuvant chemotherapy has no proven impact so far. Whether this will change with the use of more active chemotherapy or better timing of adjuvant treatment remains to be seen. Neoadjuvant chemotherapy has proven to be feasible and active also in potentially resectable tumors. Therefore, preoperative chemotherapy appears to be an attractive tool for clinical investigations also in earlier stages of gastric cancer. PMID- 8204533 TI - Adjuvant radiotherapy and chemotherapy for biliary and pancreatic cancer. AB - Due to the limited efficacy of surgery in pancreatico-biliary cancer, perioperative treatment modalities are of high clinical interest. Adjuvant chemoradiation with protracted infusion 5-FU for these tumors is an attractive direction for continued clinical research and may increase local control. Improved local control may influence survival as has been demonstrated by the results of adjuvant chemoradiation for operable rectal cancer. Newer combinations of chemotherapy and external beam radiotherapy (ExBRT) will need to be tested. The results of combined modality therapy indicate that increased normal tissue reactions occur and caution must be exercised during treatment especially in the areas of nutrition and fluid balance. New treatment strategies with electron beam IORT are also investigating higher doses of radiotherapy than those achieved with ExBRT alone in order to achieve better permanent tumor eradication. Data from our institution have demonstrated the safety of aggressive preoperative chemoradiation, surgical resection and IORT. Prophylactic hepatic and whole abdominal chemoradiation for occult liver disease needs further testing in clinical trials, since the liver is the single most frequent site of failure outside the primary site. PMID- 8204534 TI - Multimodality treatment of locally advanced pancreatic cancer. AB - BACKGROUND: The prognosis of locally advanced pancreatic cancer is poor (median survival 3-5 months). In view of the localized character of this disease several groups have explored the value of combined modality treatment. The conditions are that a good local treatment and an effective systemic treatment are available. PATIENTS AND METHODS: The results of irradiation and of chemotherapy in advanced disease are reviewed. RESULTS: An overview of combined modality treatment has been given. CONCLUSIONS: Results of combined modality treatment are superior to irradiation alone or to symptomatic treatment. PMID- 8204535 TI - Current status and future directions in the perioperative treatment of pancreatic cancer. AB - Pancreatic cancer is associated with an extremely poor prognosis. Even after resection with curative intent, the 5-year survival rates usually do not exceed 5%, and neither radiotherapy (RT) nor chemotherapy (CT) improve long term survival. Because of the poor outcome of patients with localized disease, studies should be directed to selected patients who benefit from surgery and from combined treatment of surgery with chemo-irradiation. Future developments in the treatment of locoregionally confined pancreatic cancer will have to focus on treatment modalities which improve the local tumor control as well as the control of occult distant disease. Combined CT/RT seems to be the most promising approach for these patients. However, to date there are more questions than clearcut answers about what such a multimodality treatment should look like. This concerns the selection of patients, the dosages, time schedules, and routes of administration of CT and RT. Last but not least, there is a need for more effective CT in pancreatic cancer. New drugs and multiple drug combinations should be studied in patients who are not candidates for multimodality treatment because of distant metastases. Well designed trials that address these issues are urgently needed in the forthcoming years. PMID- 8204536 TI - High dose external beam radiation therapy with or without concomitant chemotherapy for esophageal carcinoma. AB - Esophageal cancer patients treated with radiotherapy (RTx) are most often those with malignancies too extensive for surgery or those who deemed medically unsuitable for an aggressive surgical approach. Summarizing RTx series, the 2 year survival rate is in the range of 10% and at 5 years about 5%. Although not randomly compared, these results are not significantly worse than those achieved with surgery in more advanced tumors. In stage I/II tumors, more recent trials reported of 5-year survival rates varying between 12% and 20%. These data indicate that irradiation may be administered with curative intention but usually only for patients who are also candidates for primary surgery. On the other hand, modern RTx (doses > 60 Gy) +/- endoluminal after-loading may provide good palliation (relief of dysphagia) for patients with good prognostic factors such as weight loss of less than 10% body weight, good performance status, younger age, and location of the tumor. In the perioperative setting, RTx reduced the frequency of the local recurrences but did not increase the overall resection and R0 resection rates and did not improve survival due to more patients relapsing at distant sites. Combined chemoradiotherapy has shown to be superior to RTx alone with respect to local control, disease free survival and overall survival and in a marked reduction of distant failures. These data support the use of chemoradiotherapy as standard treatment of locally advanced and nonresectable esophageal cancer. They also provide a basis for randomized trials comparing chemoradiotherapy alone versus preoperative treatment modalities. PMID- 8204537 TI - Surgery for cancer of the colon and rectum. AB - Surgery is the cornerstone of treatment of primary colorectal cancer, independent of the patients age and extent of disease. In the case of locoregionally confined tumors, an en-bloc resection of the primary tumor and adequate lymph node dissection should be performed. However, this is still not generally done. A subtle surgical technique is the most important prophylaxis against local recurrences. Standardized operative techniques, extended resections and perioperative measures led to a reduction of the rate of palliative resections and to a reduction of perioperative mortality (approximately 3%). However, despite modern surgical approaches, the long term prognosis of patients with stage II/III was not essentially improved. Therefore, especially in these stages, a further improvement of the current situation can at best expected by perioperative chemotherapy +/-irradiation. PMID- 8204538 TI - Adjuvant therapy for colon adenocarcinoma: current status of clinical investigation. AB - Colorectal cancer is one of the leading causes of death in western countries. The prognosis is strongly correlated to the TNM-staging system and patients with stage T3-4 and/or N positive disease have a high risk for local or distant relapse. It is now widely accepted that patients with stage III disease should be offered postoperative adjuvant chemotherapy with 5-fluorouracil (5-FU) and levamisole by which cancer related death is reduced by 32%. The use of 5-FU plus folinic acid is based on the experience gathered in metastatic disease where its superiority over 5-FU alone has been proven in randomized trials. In the adjuvant setting, however, this regimen has only been studied in comparison to untreated controls of combined stage II and stage III patients. Due to different patient selection criteria, data are currently not directly comparable to standard 5 FU/levamisole and the results of the intergroup trial 0089 have to mature. Regional short term adjuvant treatment (7 days) seems to be as effective as long term systemic therapy (12 months). Knowledge has been accumulated within at least 8 randomized trials and the NSABP-CO2 trial, with more than 1000 patients, is now demonstrating improved survival with regional therapy applied shortly after curative resection. The EORTC has just started to randomize patients to receive systemic vs. regional therapy or both modalities and will hopefully clarify the role of either strategy. Immunotherapy with autologous tumor cell-BCG or monoclonal antibody treatment also improves patients survival and is currently investigated in randomized comparison to standard 5-FU/levamisole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204539 TI - The psychopathology of authority and its loss: the effect on a ward of losing a consultant psychiatrist. AB - A consultant psychiatrist on an in-patient psychiatric unit left temporarily for a four-week visit to Australia. Eight of 11 patients under his care developed disturbed behaviour, although all had been stable for many months before. Of the other 11 patients on the same ward, under the care of another consultant psychiatrist, only one developed similar problems over this time. It has already been well established in previous research that loss events, particularly of attachment figures, contribute to psychopathology. However, what loss events the psychiatric unit itself presents to patients, and furthermore how the loss of perhaps more distant but important figures, like consultants or senior psychiatrists, also affect patients has not been previously explored. The neglected issue of the role of authority in the therapeutic relationship as well as in psychiatric illness is discussed. It is suggested that this has important implications for psychiatric practice. PMID- 8204540 TI - Women who stab: a personal construct analysis of sexual victimization and offending behaviour. AB - The personalities and perceptions of two women with a history of very significant sexual abuse who had committed serious violent offences against 'boy friends' are investigated using role construct repertory grid (Kelly) and hypotheses developed for treatment, in particular to prevent any reoffending. The most significant dimension that emerged was in general terms that of 'abuser-victim'. It was clear that there was significant confusion about their self-perceptions with regard to these roles. They perceived themselves as abusers despite their histories of victimization. There was a high level of guilt associated with the victim role in each woman and in previous therapy simply dealing with their victim role gave rise to very disturbed self-destructive behaviour and even more guilt. The grid results enabled the abuser self-perception to be identified and treatment programmes to be developed using Ryle's cognitive-analytic therapy. Following treatment further grids and clinical evidence suggested that there were significant changes in self-perception and in behaviour. The findings were discussed and the need for further investigations suggested. PMID- 8204541 TI - The phenomenology of shame and guilt: an empirical investigation. AB - This paper explores the various literatures concerned with shame and guilt. Lewis' (1987) model of shame is outlined. The phenomena she suggested to be part of shame (feelings of helplessness, anger at others, anger at self, self consciousness and feelings of inferiority) were investigated as to their relationship with shame. Strong support for these phenomena being related to shame, but not guilt, was found. Although located in separate literatures, shame and fear of negative evaluation have considerable overlap and this study set out to explore this relationship. The study further considered the role of submissive behaviour in shame and depression. Evidence was found to support the view that submissive behaviour is involved in both shame and depression. PMID- 8204542 TI - Attentional bias, persecutory delusions and the self-concept. AB - Recent studies of cognitive processes associated with persecutory delusions suggest that such delusions are associated with abnormalities in the processing of information relevant to the self. Attention to positive and negative trait words was studied in subjects suffering from persecutory delusions, matched subjects with depressed mood and normal controls using an emotional Stroop task. Subjects were required to name the ink colours of: (i) meaningless strings of Os, (ii) low self-esteem personal adjectives, (iii) high self-esteem adjectives and (iv) neutral adjectives. subjects were also asked to rate the degree to which they endorsed as self-descriptive these and other personally descriptive adjectives. The subjects with persecutory delusions demonstrated a significantly higher rate of endorsement for positive adjectives than negative adjectives, but showed a marked degree of interference when colour-naming both positive and negative words. The relevance of these findings to a model of persecutory delusions involving the self-concept is discussed. PMID- 8204543 TI - The effects of varying auditory input on schizophrenic hallucinations: a replication. AB - The aim of this study was to investigate the effects of different types of auditory stimulation on reports of auditory hallucinations at the time of the experiment. The results showed that self-reports by seven schizophrenic patients of auditory hallucinations were reduced by different types of auditory stimulation, particularly by listening to pop music. Requiring the subject to read a passage aloud also reduced the levels reported. This study was a replication of one by Margo, Hemsley & Slade (1981) who reported similar findings. PMID- 8204544 TI - Diabetes: its differential impact on child and family. AB - We argue that there are two groups of diabetic children who cope differently with the treatment regimen, (a) those who maximize their metabolic control and whose difficulties are associated with better control, and (b) those who maintain control less tightly and whose difficulties are associated with poorer control. This hypothesis was investigated with a sample of 47 diabetic children and their mothers. Analyses confirmed the hypothesis, indicating two distinct groups based on the type of symptom (emotional versus conduct) the child exhibited. Symptom type was associated with mother's knowledge of diabetes, diabetic control, scores received on a standardized measure of psychological disturbance and diabetes specific concerns. The comparison of these two diabetic groups proved more sensitive to differences in diabetic adjustment than did comparisons made on the basis of psychiatric disturbance. PMID- 8204545 TI - Outpatient laparoscopic cholecystectomy. AB - Outpatient Laparoscopic Cholecystectomy was attempted in 98 patients selected from 266 patients presenting for elective cholecystectomy (37%). Two patients required admission following conversion to "open" Cholecystectomy, one patient was admitted for observation because of a technically difficult Laparoscopic Cholecystectomy and 16 patients were admitted because of refractory nausea and vomiting in the early post-operative period. Seventy-nine patients (81%) were able to be discharged home within 4 to 6 hours of surgery, with only one patient requiring readmission to hospital because of the onset of nausea and vomiting. There were no post-operative complications attributable to the outpatient experience. We believe this approach to elective gallbladder pathology can be safely accomplished in selected patients and will be increasingly utilized in the future. PMID- 8204546 TI - The effects of long-term graft preservation on intraoperative hemostatic changes in liver transplantation. A comparison between orthotopic and heterotopic transplantation in the pig. AB - We compared hemostatic changes during OLT and HLT after various periods of graft storage, to investigate whether the host liver in HLT protects the recipient from hemostatic deterioration induced by severe graft storage damage. In particular, the mechanism of fibrinolytic deterioration was investigated. The effect of prostaglandin E1 (PGE1) on these parameters was also studied. MATERIAL AND METHODS: 69 pigs underwent either OLT (N = 32) or HLT (N = 37) with a graft stored for 2 hr (N = 31), 24 hr (N = 16), 48 hr (N = 7), or 72 hr (N = 15). PGE1 was given intravenously to both donor and recipient animals and was added to the preservation and flushing solutions. Fibrinolysis (euglobulin clot lysis time, t PA activity and alpha 2-antiplasmin) and coagulation parameters (activated partial thromboplasmin time, prothrombin time, fibrinogen and platelet count) were measured at several intervals during transplantation. STATISTICS: Univariate non-parametric tests were used for analysis of coagulation and fibrinolysis parameters. For the three main variables- i.e., the type of transplantation, the use of PGE1, and the preservation time, multiple regression analysis was performed. RESULTS: Fibrinolytic activity increased during the anhepatic period of OLT. Graft reperfusion was followed by a rise in t-PA in both OLT and HLT. In HLT, t-PA quickly returned to normal, whereas a continuous increase was found in OLT. The coagulation parameters, in turn, remained unchanged during the anhepatic period and deteriorated in OLT compared to HLT. The duration of graft storage was directly related to the severity of the hemostatic changes, although this effect was more apparent in OLT than in HLT. CONCLUSIONS: Changes in hemostasis are more pronounced in OLT than in HLT. This suggests that the host liver protects the recipient from the effects of graft storage damage, even after long preservation times. Early postreperfusion fibrinolytic activity was presumably due to t-PA release from the graft both in OLT and HLT. The further rise t-PA in OLT might be caused by the release of cytokines from the graft, that subsequently evoke endothelial t-PA release. In HLT, t-PA and cytokines may be cleared by the native liver. No positive or negative effect of PGE1 on coagulation or fibrinolysis parameters was noticed. PMID- 8204547 TI - Neutrophil priming by cytokines in patients with obstructive jaundice. AB - Patients with obstructive jaundice frequently suffer postoperative complications. We have investigated the relationship of obstructive jaundice to the neutrophil oxidase response and the "priming" of the response by the cytokines TNF alpha, interleukin-1 (IL-1), IL-6, and IL-8. On stimulation with f-met-leu-phe (fmlp), the respiratory burst in neutrophils from jaundiced patients was greatly increased compared with controls (p < 0.01), jaundiced patients having the highest respiratory burst levels were those with the poorest prognosis. Neutrophils from controls were primed by all the cytokines tested, whereas "jaundiced" cells were primed only by IL-1, and not by TNF alpha, IL-6, or IL-8, which in fact produced slight inhibition. We conclude that neutrophils from obstructive jaundiced patients have raised oxidative responses which may be due to "pre-priming" in vivo by cytokines, such as IL-6, IL-8, or TNF alpha. This exaggeration of the oxidative response in circulating neutrophils may contribute to the peri-operate complications of patients with obstructive jaundice. PMID- 8204548 TI - Abdominal wall haematoma complicating laparoscopic cholecystectomy. AB - Of 61 consecutive patients undergoing laparoscopic cholecystectomy, 4 (6.25%) developed abdominal wall haematomas. This complication of laparoscopic cholecystectomy may occur more commonly than existing literature suggests, and manifests in the post-operative period (days 2 to 6) by visible bruising, excessive pain or an asymptomatic drop in haematocrit. It is readily confirmed by ultrasonography. While no specific treatment is necessary apart from replacement of significant blood loss, the patient requires reassurance that this apparently alarming complication will rapidly resolve. PMID- 8204549 TI - The effect of propofol on the canine sphincter of Oddi. AB - To assess the effect of propofol on the canine sphincter of Oddi(SO), sphincter of Oddi manometry (SOM) was performed in fasting dogs which had undergone cholecystectomy and placement of modified Thomas duodenal cannulae. Using two water-perfused, single-lumen manometric catheters, SO and duodenal pressures were measured simultaneously. Baseline SO activity was recorded for at least one complete interdigestive cycle followed by bolus injections of propofol (Diprivan) (N = 31) from 0.1 to 4.0 mg/kg during Phase I of the Migrating Motor Complex (MMC). When propofol was administered in bolus doses < or = 0.4 mg/kg, no change in SO or duodenal motor function was seen. In doses > or = 0.5 mg/kg, SO basal pressure, amplitude, and frequency of contractions increased significantly. Increases in duodenal activity paralleled SO activity. Our results suggest that propofol in low doses may be useful for sedation during Sphincter of Oddi manometry in humans. Further studies of the effect of propofol on the human sphincter of Oddi are warranted. PMID- 8204550 TI - Amebic liver abscess with intra-biliary rupture. AB - The case of a large amebic liver abscess with an atypical presentation is reported. High output bile drainage persisted after ultrasound guided percutaneous catheter drainage because of a preexisting communication of the abscess with the right hepatic ductal system. The abscess was managed successfully by surgical evacuation and internal drainage into a defunctioned jejunal loop. PMID- 8204551 TI - Intraperitoneal rupture of ectopic varices--a rare complication of portal hypertension. AB - A 50 year old man presented with sudden abdominal pain, abdominal distension and shock. At emergency laparotomy a large amount of blood was found in the peritoneal cavity. There was micronodular cirrhosis of the liver and the spleen was enlarged. The bleeding was traced to distended veins in the right paracolic gutter which were oversewn and the abdomen closed. A coagulopathy was diagnosed and treatment including high dose aprotinin commenced. However, he continued to bleed and at a second laparotomy the area of previous haemorrhage was packed. Further deterioration continued until death 12 hours later. Intraperitoneal haemorrhage from ectopic varices is a rare occurrence. There is a high mortality rate usually due to an advanced coagulopathy. This is the first report of aprotinin being used in an attempt to treat this. On the basis of this report aprotinin would not seem to be of benefit for this condition. PMID- 8204552 TI - Cholecystobronchocolic fistula: a late complication of biliary sepsis. Case report of diagnosis and management. AB - A case of a 48 year old woman presenting with bilioptysis due to a cholecystobronchocolic fistula is reported. Bilioptysis is a rare complication of biliary fistulae, with a high mortality due to chemical pneumonitis. Bronchospasm and rapid respiratory failure may ensue if aggressive management is not adopted. The site of fistulation is established by cholangiography, preferably by the percutaneous transhepatic route. Continued biliary drainage can lead to closure of these fistulae, or allow sufficient improvement in clinical condition to allow definitive surgery to be performed electively. PMID- 8204553 TI - Sclerotherapy versus transection for acute variceal bleeding. PMID- 8204554 TI - Two varieties of intrahepatic cholangiocarcinoma. PMID- 8204555 TI - Technique of vascular isolation for liver resection. PMID- 8204556 TI - Liver resection under inflow occlusion: a bloodless operation? PMID- 8204557 TI - Tense ascites in cirrhosis: paracentesis with albumin infusion versus spontaneous ascites filtration. PMID- 8204558 TI - 1994 Annual meeting of the American Society of Regional Anesthesia. Chicago, Illinois, April 6-10, 1994. Abstracts. PMID- 8204559 TI - [Importance of AgNOR analysis in malignant tumors]. AB - For the assessment of proliferative activity of malignant tumors several methods can be used. The method having been used at first has been the determination of mitotic index, playing an important role as a part of various grading systems until now. Besides of DNA cytometry, flow cytometry, determination of bromodeoxyuridine labeling index (BrdUr-LI) and immunohistochemical analysis of proliferation-associated antigens (e.g. Ki-67, PCNA), for several years AgNOR analysis has been used as a new technique, giving reproducible, exact results of proliferative activity of malignant tumors. Valuable information about proliferative activity of cells can be gained already by counting the AgNOR number per nucleus. Moreover the use of digital image analysis provides information about size and distribution of AgNORs. Evidently these data are more important than AgNOR number. In the hands of experienced pathologists and under standardized conditions AgNOR staining and AgNOR quantification are a valuable completion of established methods. PMID- 8204560 TI - Structure and molecular organization of the nucleolus. AB - The aim of this paper is to give a short review on the nucleolus. In particular, we focused on the relationship of nucleolar ultrastructure with rRNA synthesis and processing. We also gave rapid data on organization of rRNA genes. Finally, we also focused on AgNOR proteins and the organization of "AgNOR granules". PMID- 8204561 TI - A clinical evaluation of the Neurobehavioral Cognitive Status Examination in a general psychiatric inpatient population. AB - The Neurobehavioral Cognitive Status Examination (NCSE) is a structured test of cognitive functioning. The NCSE assesses a broader range of cognitive functioning than the Mini-Mental State Examination (MMSE), but remains brief enough to be administered at the bedside in clinical settings. The purpose of this study was to assess the sensitivity, specificity, predictive value and reliability of the NCSE as a clinical case-finding instrument for DSM-III-R defined organic mental disorders in psychiatric inpatients. Validity was assessed by comparing the results of the test (interpreted as "pass" or "fail") to a blind clinical assessment by an experienced psychiatrist. The NCSE was found to have superior sensitivity to the MMSE (83% versus 43%), but inferior specificity (47% versus 97%). The low specificity resulted in a positive predictive value of only 24%. The NCSE had good test-retest reliability (Kappa = .69), but the inter-rater reliability was not as good (Kappa = 0.57). The NCSE was too non-specific to be used as a case-finding instrument for organic mental disorders. In conclusion, although clinicians may find the NCSE to be a valuable instrument for the assessment of cognitive function, it cannot be used as a screening or case finding instrument for organic disorders among psychiatric inpatients. PMID- 8204562 TI - Comparative study of platelet 3H-paroxetine and 3H-imipramine binding in panic disorder patients and healthy controls. AB - High affinity 3H-paroxetine and 3H-imipramine binding sites were simultaneously studied in platelets of 29 untreated patients with panic disorder and 12 healthy controls. The maximum number of binding sites (Bmax) was found to be significantly lower in the panic patients compared to the controls using either ligand. No difference in the Kd values between the groups of subjects was found. The disturbance of serotonin neurotransmission in panic disorder--decrease in Bmax values--may be either a consequence or a reason of serotonergic dysfunction. PMID- 8204563 TI - Tryptophan in the treatment of late luteal phase dysphoric disorder: a pilot study. AB - Thirteen patients diagnosed during two menstrual cycles as suffering from late luteal phase dysphoric disorder were then followed in an open pilot study for a further three cycles. During one complete cycle, baseline levels of symptoms were obtained. During the next three cycles, the patients were treated with L tryptophan, six grams per day. L-tryptophan treatment was associated with a significant amelioration of symptoms with only mild side effects. These data suggest that L-tryptophan should be tested at a dose of six grams of L-tryptophan per day in a placebo-controlled study in patients with late luteal phase dysphoric disorder who suffer from symptoms such as depression, irritability, insomnia and carbohydrate craving, which may respond to potentiation of serotonin function. PMID- 8204564 TI - The responsiveness of cerebral cortical adrenergic receptors after chronic administration of atypical antidepressant mianserin. AB - The aim of this study was to evaluate the effect of mianserin, a second generation tetracyclic antidepressant agent, on the receptors' and second messenger systems related to noradrenergic transmission in the cerebral cortex of the rat. In in vitro experiments we confirmed that mianserin binds with equal potency to alpha 1- and alpha 2-adrenoceptors and does not affect beta 1 adrenoceptors. It inhibited the noradrenaline-stimulated inositol phosphate accumulation and did not change the cyclic AMP responses to noradrenaline and isoproterenol. The drug attenuated the inhibitory action of PKC activator, TPA, on the noradrenergic response from alpha 1-adrenoceptor and the potentiating action of TPA on the cyclic AMP stimulated with noradrenaline and isoproterenol. In chronic experiments we have found that, in contrast to most antidepressants, chronic treatment with mianserin does not produce strong beta-downregulation, but increases the maximal inositol phosphate response from alpha 1-adrenoceptor. The results indicate that alpha 1-upregulation might be a characteristic of those efficient antidepressant drugs which do not produce a strong beta-downregulatory effect. PMID- 8204565 TI - Age-related changes in peripheral benzodiazepine receptors of human platelets. AB - Using 3H-PK 11195 as radioligand, the number and affinity of peripheral benzodiazepine receptors in platelets of 15 elderly healthy subjects were compared to those of 15 young subjects. The results showed that the dissociation constant (Kd) was significantly higher in the elderly than in the young subjects, while the density of binding sites did not differ. These findings suggest that the age-related changes in peripheral benzodiazepine receptors may be coupled with secondary changes in their hypothesized functions. PMID- 8204566 TI - Malformations of the septum pellucidum: two distinctive cases in association with schizophrenia. AB - Two patients with schizophrenia had markedly abnormal neuroimaging studies; one was found to have a large, cystic cavum vergae, while the other demonstrated complete agenesis of the septum pellucidum with a monoventricular system. The increased prevalence of developmental abnormalities of midline forebrain structure in patients with schizophrenia suggests that dysgenesis of these structures may be contributory to the neurobiology of schizophrenia and other psychotic disorders. PMID- 8204567 TI - Famotidine as an adjunct treatment of resistant schizophrenia. AB - Some patients suffering from schizophrenia fail to respond to or tolerate adequate doses of available antipsychotic medications. Thus, innovative pharmacotherapeutic approaches, such as augmentation strategies, play an important role in the management of these treatment-resistant patients. A recent case report suggested that the administration of famotidine to a patient suffering from schizophrenia with peptic ulcer disease was associated with improvement in the deficit symptoms of schizophrenia. Famotidine is a potent highly selective H2 receptor antagonist which crosses the blood-brain barrier. Impressed by this finding, famotidine was prescribed to some of our treatment resistant patients suffering from schizophrenia who demonstrated significant deficit symptoms of schizophrenia. The subjects were 12 (eight male, four female) treatment-resistant psychotic patients whose antipsychotic medications were augmented with famotidine in an open trial. They ranged in age from 21 to 48 years with a mean age of 32.75 years. Seven of the 12 subjects made significant improvement resulting in discharge from hospital. Paranoid disturbances as well as absence of comorbid substance use were predictors of good response to famotidine augmentation of the antipsychotic medications. The results implied that H2 receptor activity in the brain might play a role in the pathogenesis of deficit syndromes in schizophrenia. Further studies of this strategy are recommended, since it may open a window of understanding of the negative (deficit) syndrome and its treatment. PMID- 8204568 TI - Platelet serotonergic markers in psychiatric disorders: use, abuse and limitations. PMID- 8204569 TI - [The approach of cognitive neuropsychology toward the studies on autism]. PMID- 8204570 TI - The chloroperoxidase-catalyzed oxidation of phenols. Mechanism, selectivity, and characterization of enzyme-substrate complexes. AB - The reactivity of a series of para-substituted phenolic compounds in the peroxidation catalyzed by chloroperoxidase was investigated, and the results were interpreted on the basis of the binding characteristics of the substrates to the active site of the enzyme. Marked selectivity effects are observed. These operate through charge, preventing phenolic compounds carrying amino groups on the substituent chain to act as substrates for the enzyme, and through size, excluding potential substrates containing bulky substituents to the phenol nucleus. Also, chiral recognition is exhibited by chloroperoxidase in the oxidation of N-acetyltyrosine, where only the L isomer is oxidized. Kinetic measurements show that, in general, the efficiency of chloroperoxidase in the oxidation of phenols is lower than that of horseradish peroxidase. Paramagnetic NMR spectra and relaxation rate measurements of chloroperoxidase-phenol complexes are consistent with binding of the substrates close to the heme, in the distal pocket, with the phenol group pointing toward the iron atom. On the other hand, phenolic compounds which are not substrates for chloroperoxidase bind to the enzyme with a much different disposition, with the phenol group very distant from the iron and probably actually outside the active-site cavity. PMID- 8204571 TI - Blue halorhodopsin from Natronobacterium pharaonis: wavelength regulation by anions. AB - Halorhodopsin, the chloride pump from Natronobacterium pharaonis (pharaonis hR), was isolated under conditions of low ionic strength. The quotient between the optical densities of pharaonis hR in 4 M NaCl at 280 and 577 nm amounts to 1.1, indicating a high purity of the protein and integrity of the chromophore. Gel filtration chromatography of the purified pharaonos hR at neutral pH and in the absence of inorganic salts leads to a shift to the absorption maximum to 600 nm (pharaonis hRblue). The purple color can be regained by the addition of anions such as chloride, iodide, azide, nitrate, and also fluoride. The absorption maxima are dependent on the nature of the anion and the pH. At pH 7, sulfate does not influence the 600-nm absorption, while at pH 4.5 the absorption maximum is shifted to 581 nm. The blue form of halorhodopsin (pharaonis hRblue) was titrated with different sodium salts, such as chloride, azide, and nitrate. The half maximal binding is in the millimolar range, with Br < Cl < NO3 < N3 < BrO3. Deprotonation of the Schiff base can be accomplished by treatment of pharaonis hR or pharaonis hRblue with base. The apparent pK of the Schiff base in pharaonis hRblue was determined to be 8.5. The pK shifted to 8.0 in the presence of 150 mM Na2SO4, whereas the pK of pharaonis hR in 150 mM NaCl is 9.6. In the photocycle of the chloride- and nitrate-containing pharaonis hR, a species similar to hR520 could be detected. Pharaonis hR reconstituted with azide shows photochemical reactions similar to the photocycle of bacteriorhodopsin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204572 TI - Evidence for a ternary complex formed between flavodoxin and cytochrome c3: 1H NMR and molecular modeling studies. AB - Small electron-transfer proteins such as flavodoxin (16 kDa) and the tetraheme cytochrome c3 (13 kDa) have been used to mimic, in vitro, part of the complex electron-transfer chain operating between substrate electron donors and respiratory electron acceptors, in sulfate-reducing bacteria (Desulfovibrio species). The nature and properties of the complex formed between these proteins are revealed by 1H-NMR and molecular modeling approaches. Our previous study with the Desulfovibrio vulgaris proteins [Moura, I., Moura, J.J. G., Santos, M.H., & Xavier, A. V. (1980) Cienc. Biol. (Portugal) 5, 195-197; Stewart, D.E. LeGall, J., Moura, I., Moura, J. J. G., Peck, H.D. Jr., Xavier, A. V., Weiner, P. K., & Wampler, J.E. (1988) Biochemistry 27, 2444-2450] indicated that the complex between cytochrome c3 and flavodoxin could be monitored by changes in the NMR signals of the heme methyl groups of the cytochrome and that the electrostatic surface charge (Coulomb's law) on the two proteins favored interaction between one unique heme of the cytochrome with flavodoxin. If the interaction is indeed driven by the electrostatic complementarity between the acidic flavodoxin and a unique positive region of the cytochrome c3, other homologous proteins from these two families of proteins might be expected to interact similarly. In this study, three homologous Desulfovibrio cytochromes c3 were used, which show a remarkable variation in their individual isoelectric points (ranging from 5.5 to 9.5). On the basis of data obtained from protein-protein titrations followed at specific proton NMR signals (i.e., heme methyl resonances), a binding model for this complex has been developed with evaluation of stoichiometry and binding constants. This binding model involves one site on the cytochromes c3 and two sites on the flavodoxin, with formation of a ternary complex at saturation. In order to understand the potential chemical form of the binding model, a structural model for the hypothetical ternary complex, formed between one molecule of Desulfovibrio salexigens flavodoxin and two molecules of cytochrome c3, is proposed. These molecular models of the complexes were constructed on the basis of complementarity of Coulombic electrostatic surface potentials, using the available X-ray structures of the isolated proteins and, when required, model structures (D. salexigens flavodoxin and Desulfovibrio desulfuricans ATCC 27774 cytochrome c3) predicted by homology modeling. PMID- 8204573 TI - Solution structure of horse heart ferrocytochrome c determined by high-resolution NMR and restrained simulated annealing. AB - A model for the solution structure of horse heart ferrocytochrome c has been determined by nuclear magnetic resonance spectroscopy combined with hybrid distance geometry-simulated annealing calculations. Forty-four highly refined structures were obtained using a total of 1940 distance constraints based on the observed magnitude of nuclear Overhauser effects and 85 torsional angle restraints based on the magnitude of determined J-coupling constants. The all residue root mean square deviation about the average structure is 0.47 +/- 0.09 A for the backbone N, C alpha, and C' atoms and 0.91 +/- 0.07 A for all heavy atoms. The overall topology of the model for solution structure is very similar to that seen in previously reported models for crystal structures of homologous c type cytochromes. However, a detailed comparison between the model for the solution structure and the available model for the crystal structure of tuna ferrocytochrome c indicates significant differences in a number of secondary and tertiary structural features. For example, two of the three main helices display 3(10) to alpha-helical transitions resulting in bifurcation of main-chain hydrogen bond acceptor carbonyls. The N- and C-terminal helices are tightly packed and display several interhelical interactions not seen in previously reported models. The geometry of heme ligation is well-defined and completely consistent with the crystal structures of homologous cytochromes c as are the locations of four of six structural water molecules. Though the total solvent accessible surface area of the protoporphyrin ring is similar to that seen in crystal studies of tuna ferrocytochrome c, the distribution is somewhat different. This is mainly due to a difference in packing of residues Phe-82 and Ile-81 such that Ile-81 crosses the edge of the heme in the solution structure. These and other observations help to explain a range of physical and biological data spanning the redox properties, folding, molecular recognition, and stability of the protein. PMID- 8204574 TI - Chromophore topography and exciton splitting in phycocyanin 645. AB - The biliprotein phycocyanin 645 has been purified from a photosynthetic cryptomonad Chroomonas species. It is composed of two copies each of two polypeptides (alpha and beta); each alpha polypeptide has one chromophore, and each beta polypeptide has three. There are one cryptoviolin and two phycocyanobilins on each beta polypeptide and one 697-nm bilin on each alpha polypeptide for a total of eight chromophores on the protein. Circular dichroism (CD) spectroscopy has been used to investigate the arrangement of these chromophores. Comparisons among the intact protein (alpha 2 beta 2) and various urea-treated products have yielded a tentative model for chromophore topography. The six chromophores on the two beta polypeptides are segregated into three pairs. The chromophores of each pair are close enough to experience electronic interactions. One pair, consisting of the two cryptoviolins, produces exciton splitting on the blue edge of the visible CD spectrum, and the two pairs of phycocyanobilins cause exciton splitting on the red edge of this spectrum. Deconvolution shows that the CD spectrum of each pair has a positive and a negative band, which are nearly conservative as expected for exciton coupling. The two chromophores on the alpha polypeptides are more isolated. The pairing of cryptoviolin chromophores occurs across two beta polypeptides, but the more likely position of each of the two pairs of phycocyanobilins is probably not across a beta-beta interface but within a single beta polypeptide. The exciton splitting events both increase the range of visible light absorption for the protein and establish the routes of exciton migration through the protein. PMID- 8204575 TI - An NMR-derived model for the solution structure of oxidized putidaredoxin, a 2 Fe, 2-S ferredoxin from Pseudomonas. AB - A model for the solution structure of oxidized putidaredoxin (Pdx), a 106-residue globular protein containing a Fe2S2 cluster, has been determined using homonuclear NMR methods. Pdx is the first of the class of Fe2S2Cys4 ferredoxins which act as electron-transfer partners for P-450 monooxygenases to be structurally characterized, and no crystal structure has been determined for Pdx or for any closely homologous protein. Pdx is the physiological redox partner of cytochrome P-450cam. A total of 878 NOE distance constraints, 66 phi angular constraints derived from NH-C alpha H coupling constants, and five paramagnetic broadening constraints were used in simulated annealing structural refinements to obtain a family of structures with pairwise rms deviations of 1.14 A for backbone atoms and 1.80 A for all non-hydrogen atoms. Paramagnetic broadening of resonances within a ca. 8-A radius of the metal cluster prevents the use of NMR derived constraints in this region of the protein; structural constraints used to model the environment of the metal cluster were obtained from site-directed mutagenesis and model compounds and by comparison with known ferredoxin structures. Pdx retains a similar folding topology to other structurally characterized Fe2S2Cys4 ferredoxins but differs from the other ferredoxins in containing a significantly more compact structure in the C-terminal half of the protein. PMID- 8204576 TI - Redox-dependent 1H NMR spectral features and tertiary structural constraints on the C-terminal region of putidaredoxin. AB - Putidaredoxin (Pdx) is a 106-residue Fe2S2 ferredoxin which acts as the physiological reductant and effector of cytochrome P-450cam. Pdx has two accessible oxidation states, Fe+3-Fe+3 (oxidized) and Fe+3-Fe+2 (reduced), and exhibits redox-dependent binding affinities for cytochrome P-450cam, with reduced Pdx binding over 100-fold more tightly than oxidized Pdx to the oxidized cytochrome P-450cam [Hintz, M. J., Mock, D. M., Peterson, L. L., Tuttle, K., & Peterson, J. A. (1982) J. Biol. Chem. 257, 14324-14332]. The analysis of two dimensional 1H NMR experiments has yielded sequential 1H resonance assignments for the diamagnetic regions of the reduced form of Pdx, which are compared to those of oxidized Pdx, described previously [Ye, X. M., Pochapsky, T. C., & Pochapsky, S. S. (1992) Biochemistry 31, 1961-1968]. Increased unpaired electron spin density on the metal cluster in reduced relative to oxidized Pdx increases the number of 1H resonances which are broadened by the metal cluster, and the pattern of paramagnetic broadening provides information concerning the placement of the metal cluster within the protein. Two-dimensional exchange experiments on half-reduced samples of Pdx indicate that electron self-exchange is slow on the chemical shift time scale, with a second-order rate constant < or = 66 M-1 s-1 at 290 K. Spectral changes unrelated to increases in unpaired electron-spin density are also observed. The largest changes of this type are observed for features structurally contiguous with the C-terminal region Pro 102-Trp 106. The C terminal residue Trp 106 has been implicated in binding to cytochrome P 450cam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204577 TI - Activation of CYP3A4: evidence for the simultaneous binding of two substrates in a cytochrome P450 active site. AB - A unique characteristic of the CYP3A subfamily of cytochrome P450 enzymes is their ability to be activated by certain compounds. It is reported that CYP3A4 catalyzed phenanthrene metabolism is activated by 7,8-benzoflavone and that 7,8 benzoflavone serves as a substrate for CYP3A4. Kinetic analyses of these two substrates show that 7,8-benzoflavone increases the Vmax of phenanthrene metabolism without changing the Km and that phenanthrene decreases the Vmax of 7,8-benzoflavone metabolism without increasing the Km. These results suggest that both substrates (or substrate and activator) are simultaneously present in the active site. Both compounds must have access to the active oxygen, since neither phenanthrene nor 7,8-benzoflavone can competitively inhibit the other substrate. These data provide the first evidence that two different molecules can be simultaneously bound to the same P450 active site. Additionally, structure activity relationship studies were performed with derivatives of 7,8-benzoflavone structure. The effects of 13 different compounds on the regioselectivity of phenanthrene, chrysene, and benzo[a]pyrene metabolism were determined. Of the 13 compounds studied, 6 were activators, 2 were partial activators, and 5 were inhibitors. Analyses of the data suggest that (1) naphthalene substituted with a ketone in the 2-position can activate 3A4 and (2) the presence of an activator results in a narrower effective substrate binding site. Since the CYP3A enzymes are very important in drug metabolism, the possibility of activation, and autoactivation, must be considered when in vitro-in vivo correlations are made and when possible drug interactions are considered. PMID- 8204578 TI - Identification of the site of [alpha-32P]ATP adduct formation in the ArsA protein. AB - The ArsA protein, the catalytic subunit of the oxyanion-translocating ATPase encoded by the bacterial plasmid-encoded ars operon, and truncated derivatives were labeled with alpha-[32P]ATP. The labeled polypeptides were cleaved with cyanogen bromide. From gas-phase microsequencing the site of labeling was deduced to lie within residues 283-323 of the ArsA protein, a region postulated to be in a flexible linker connecting the two homologous halves of the ArsA protein. PMID- 8204579 TI - Identification of serine-143 as the most likely precursor of dehydroalanine in the active site of histidine ammonia-lyase. A study of the overexpressed enzyme by site-directed mutagenesis. AB - The gene coding for histidase (histidine ammonia-lyase, HAL, EC 4.3.1.3) was isolated from a lambda-EMBL3 genomic library from Pseudomonas putida nicII and subcloned into the expression vector pT7-7. Transformation of Escherichia coli BL21 (DE3) cells with the recombinant vector led to the expression of catalytically active histidase amounting to 20-30% of the total soluble protein in the crude cell extract. A new rapid and highly efficient isolation procedure is described leading to electrophoretically homogeneous histidase within 1.5 days. Six grams of E. coli BL21 (DE3) cells (wet weight) gives approximately 100 mg of homogeneous histidase with a specific activity of 27 IU/mg. To investigate the possible role of serine as a precursor of dehydroalanine in the active site of histidase, each of the four serines, conserved in all known histidases and phenylalanine ammonia-lyases, was consecutively changed to alanine by site directed mutagenesis. The resulting mutant genes were subcloned into the expression vector pT7-7 and were assayed for histidase activity. The catalytic activities of the four mutants and of wild-type histidase were compared. The Km and Vmax values of the overexpressed mutants S112A, S393A, and S418A and wild type histidase did not show any significant differences. Mutant S143A, however, was devoid of catalytic activity (< 0.01%), pointing to the outstanding importance of this serine for the formation of an active enzyme. We conclude that serine-143 is the most probable precursor of the active-site dehydroalanine. The role of serine-143 in the biosynthesis of active histidase is discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204580 TI - Mutations affecting transition-state stabilization by residues coordinating zinc at the active site of cytidine deaminase. AB - Cytidine deaminase from Escherichia coli contains 1 mol of tightly bound zinc per enzyme subunit (Yang, C., Carlow, D., Wolfenden, R., & Short, S.A. (1992) Biochemistry 31, 4168-4174). When the metal liganding residues Cys-129 and Cys 132 were replaced by Ala, and His-102 was replaced by Ala, Asn, or Gln, deaminase activities of cell extracts containing these mutant enzymes were decreased by several orders of magnitude relative to that of the wild-type enzyme. After purification, each mutant protein was found to contain less than 0.2 mol of zinc per enzyme subunit, except mutant H102Q, which contained 1 mol of zinc per subunit. The activity of each mutant enzyme increased in the presence of added zinc but never attained wild-type activity. Mutant H102N was unique in that this protein could be purified as a stable apoenzyme, activated by added zinc, and then inhibited by EDTA. This mutant enzyme bound zinc with an apparent Kd value of 6.0 x 10(-10) M and regained maximal activity in the presence of 1 mol of zinc per subunit. Affinities of the mutant cytidine deaminases for the transition state analogue, 5-fluoropyrimidin-2-one ribonucleoside (3,4) hydrate, were found to decrease in rough proportion to kcat/Km over a range spanning several orders of magnitude. This variation in catalytic efficiency arose mainly from effects on kcat, indicating the involvement of zinc coordination in the catalytic process rather than in substrate binding. PMID- 8204581 TI - Intimate relation between cyclooxygenase and peroxidase activities of prostaglandin H synthase. Peroxidase reaction of ferulic acid and its influence on the reaction of arachidonic acid. AB - The oxidation of ferulic acid by hydrogen peroxide catalyzed by prostaglandin H synthase follows a modified ping-pong irreversible mechanism, as is the case for classical peroxidases. The rate constant for the reaction of prostaglandin H synthase with hydrogen peroxide, determined from steady-state results, is (1.31 +/- 0.1) x 10(6) M-1 s-1, and for the reaction of prostaglandin H synthase compound II with ferulic acid it is (5.5 +/- 0.3) x 10(6) M-1 s-1. Cyclooxygenase and peroxidase functions of prostaglandin H synthase were studied by comparing the initial rates of reaction of the cyclooxygenase substrate, arachidonic acid, and a peroxidase reducing substrate, ferulic acid, in mixtures of the two substrates. For both an equimolar ratio of arachidonic and ferulic acids and ferulic acid in excess of arachidonic acid a stimulation of the cyclooxygenase reaction is observed. The concentration of ferulic acid necessary to produce 50% stimulation of 0.2 mM arachidonic acid oxidation is 0.14 +/- 0.02 mM. A striking feature of our results is that prostaglandin H synthase catalyzes oxidation of the two substrates in a constant and fixed molar ratio of ferulic acid to arachidonic acid of 2:1, despite widely different starting concentrations. If arachidonic acid is in excess of ferulic acid, enzyme inactivation occurs. The results can be explained by an interconnected cyclooxygenase-peroxidase unbranched free radical mechanism in which arachidonic acid reacts with either the ferryl oxygen or the porphyrin pi-cation radical part of a conventional peroxidase compound I (a FeIV = O porphyrin pi-cation radical) and ferulic acid reacts with compound II (FeIV = O).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204583 TI - Identification and structural determination of the KDN-containing N-linked glycan chains consisting of bi- and triantennary complex-type units of KDN-glycoprotein previously isolated from rainbow trout vitelline envelopes. AB - KDN-gp, which is the unique glycoprotein of the rainbow trout egg envelope, was shown to have a small amount of N-linked oligosaccharide units in addition to a large number of O-linked glycan units. Structural analysis based on chemical analysis in combination with 400 MHz 1H NMR spectroscopy revealed the presence of fully KDNosylated bi- and triantennary complex-type oligosaccharide chains, mostly fucosylated at the innermost GlcNAc residue and bisected by the GlcNAc residue linked beta 1-->4 to the beta-Man residue. The structures thus determined represent the first demonstration of N-linked glycan unit containing the KDN residues in the KDN-containing glycoproteins (see Chart 1). The KDN-gp of the rainbow trout egg envelope is a molecule that is present in the second layer of the vitelline envelope but is exposed to the outer surface around the micropyle through which sperm can get in at fertilization. Like human hematopoietic cell surface glycoproteins such as glycophorin A and leukosialin, KDN-gp, which is now characterized to contain N-linked complex-type glycan chains as minor components, is heavily O-glycosylated with alpha 2-->8-linked oligo/polyKDN-containing glycan units attached O-glycosidically to Ser/Thr residues. Although little is known about the functional roles of these glycan chains, KDN-gp appears to form a model for further study on the function of cell surface receptor for sperm in fertilization. PMID- 8204582 TI - Evidence that the nature of amino acid residues in the P3 position directs substrates to distinct catalytic sites of the pituitary multicatalytic proteinase complex (proteasome). AB - Cleavage of bonds after neutral amino acids by the multicatalytic proteinase complex (MPC) has been recently shown to be catalyzed by at least three distinct components [Orlowski, M., Cardozo, C., & Michaud, C. (1993) Biochemistry 32, 1563 1572]. One component, designated as chymotrypsin-like (ChT-L), cleaves peptide bonds on the carboxyl side of hydrophobic residues and is also active toward peptidyl-arylamide bonds. A second component, designated as branched-chain amino acid preferring (BrAAP), and a third component, designated as small neutral amino acid preferring (SNAAP), cleave preferentially bonds on the carboxyl side of branched-chain amino acids and between small neutral amino acids, respectively. Evidence indicates that the BrAAP component is a major factor responsible for degradation of protein by the MPC. The purpose of the present study was to identify the structural requirements that determine the involvement of these components in cleavage of peptides after different neutral amino acids. A series of substrates was synthesized with the aim of probing the role of residues beyond those flanking the scissile bond in directing substrates to defined catalytic sites. The data indicate that a proline or glycine residue in the P3 position directs the substrate to the catalytic site of the BrAAP component provided that a branched-chain amino acid is present in the P1 position. A proline residue in P3 is also important for involvement of the SNAAP component in substrate degradation. The presence of this residue interferes with substrate binding to the catalytic site of the ChT-L activity, even in the presence of a phenylalanine residue in the P1 position.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204584 TI - Characterization of hydrolysis and transglycosylation by testicular hyaluronidase using ion-spray mass spectrometry. AB - Various oligosaccharides from hyaluronic acid, which were fluorescence-labeled and blocked by pyridylamination at the reducing terminal, were incubated as substrates or acceptors with bovine testicular hyaluronidase. Fluorescence labeled reaction products in the reaction mixture were monitored selectively and directly by ion-spray mass spectrometry without chemical derivatization. As a result, several features of the relationship between oligosaccharides, substrates, and testicular hyaluronidase were clarified. When hexasaccharides or larger oligosaccharides having D-glucuronic acid at the nonreducing terminal were used as substrates, they were hydrolyzed sequentially to disaccharides from the nonreducing terminal, and these disaccharides were then transferred to other hexasaccharides. On the other hand, when heptasaccharides or larger oligosaccharides having N-acetyl-D-glucosamine at the nonreducing terminal were used as substrates, trisaccharides were released from the nonreducing terminal, and then also transferred to other hexasaccharides, thus forming nonasaccharides. Thus, the relationship between hydrolysis and transglycosylation reactions with testicular hyaluronidase was characterized using ion-spray mass spectrometry. PMID- 8204585 TI - Kinetics of hydrolysis of dansyl peptide substrates by thermolysin: analysis of fluorescence changes and determination of steady-state kinetic parameters. AB - The stopped-flow fluorescence technique has been used to study the hydrolysis of 10 dansyl peptides by thermolysin. The origin of the fluorescence changes observed during the reactions has been investigated in detail. Depending on the substrate and the excitation wavelength, the dansyl fluorescence changes observed arise either from energy transfer (maximal at lambda ex = 230 and 280 nm) between Trp residues of thermolysin and the dansyl group of the substrate in enzyme substrate (ES) complexes or from both sources. These excitation (maximal at lambda ex = 245 and 340 nm) of the free substrate and product, or from both sources. These two types of fluorescence signals reflect the concentrations of ESi and free substrate, respectively. Both types of fluorescence changes have been used to monitor the reaction progress, and different mathematical formalisms have been used to determine the kinetic parameters for the reactions with results that are in good agreement. The efficiency of Trp quenching by a series of five dansyl tripeptides is shown to be related to the fractional saturation of enzyme and follows the KM-1 values for the substrates. The quenching efficiency for a dansyl tetrapeptide is weaker due to the greater distance between the dansyl group and the Trp-115 donor in thermolysin. On the basis of these studies, substrates capable of supporting more detailed kinetic studies of thermolysin have been identified. PMID- 8204586 TI - Differential effect of halide anions on the hydrolysis of different dansyl substrates by thermolysin. AB - The effect of sodium halide salts on the hydrolysis of three of the dansyl (Dns) peptide substrates described in the previous paper (Yang & Van Wart, 1994) by thermolysin have been studied. Increasing concentrations of sodium chloride decrease the KM value for the hydrolysis of the tripeptides Dns-Gly-Phe-Ala and Dns-Ala-Phe-Ala but leave kcat unaltered. This kinetic behavior is described by a nonessential activation mechanism in which chloride binds preferentially to the enzyme-substrate complex. Similar trends are found for the sodium bromide and fluoride salts. In contrast, sodium chloride decreases both KM and kcat almost equally for the hydrolysis of Dns-Ala-Ala-Phe-Ala, leaving kcat/KM unchanged. Thus, chloride is an uncompetitive inhibitor of this substrate. Molecular modeling studies have been carried out in order to explain the effect of chloride on the binding of these dansyl peptides. The decrease in KM for the hydrolysis of all three substrates is attributed to an interaction of chloride with Arg-203 located in the active site to stabilize the enzyme-substrate complexes. The differential effect of chloride on the kcat values for the hydrolysis of the dansyl tripeptides vs dansyl tetrapeptide is related to differences in binding on the Pn side of the substrates. The tripeptides are predicted to bind to the active site of thermolysin in a single low-energy conformation. However, there are two populations of low-energy binding modes for the tetrapeptide, one of which is believed to be a more productive binding mode.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204587 TI - Inhibition of glyceraldehyde-3-phosphate dehydrogenase by pentalenolactone. 2. Identification of the site of alkylation by tetrahydropentalenolactone. AB - Incubation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with the antibiotic pentalenolactone (3) results in time-dependent, irreversible inhibition of GAPDH by modification of a single Cys residue in each subunit of the homotetrameric enzyme. Reduction of pentalenolactone with tritium gas gave [2,3,7,8-3H4]tetrahydropentalenolactone (7), which also exhibited time-dependent, irreversible inactivation of GAPDH. The site of covalent attachment of 7 was determined. Tryptic digestion of inactivated GAPDH and purification of the resultant products by reverse-phase HPLC gave a single labeled peptide. Amino acid sequence analysis of the radioactive peptide gave Ile-Val-Ser-Asn-Ala-Ser-X Thr-Thr-Asn-(...). This sequence is identical to the highly conserved region from Ile-143 to Asn-152 in pig muscle GAPDH, except for the active site Cys-149 to which the tetrahydropentalenolactone was covalently bound. Molecular modeling was used to compare both pentalenolactone (3) and heptelidic acid (4), a mechanistically related inactivator of GAPDH, with the normal substrate, glyceraldehyde 3-phosphate (1). Finally, pentalenolactone was shown by reaction with model thiols to undergo epoxide ring opening exclusively by nucleophilic attack at the primary carbon, C-10. PMID- 8204588 TI - Identification of possible inhibitory reactive centers in thrombospondin 1 that may bind cathepsin G and neutrophil elastase. AB - Thrombospondin 1 is a multidomain trimeric glycoprotein from platelets and a variety of normal and transformed cells of both mesenchymal and epithelial origin, which functions in cell adhesion and cell-cell interactions. We have recently shown that human thrombospondin 1 binds and inhibits the neutrophil enzymes, neutrophil elastase [Hogg, P.J., Owensby, D.A., Mosher, D.F., Misenheimer, T.M., & Chesterman, C.N. (1993a) J. Biol. Chem. 268, 7139-7146] and cathepsin G [Hogg, P.J., Owensby, D.A., & Chesterman, C.N. (1993b) J. Biol. Chem. 268, 21811-21818]. One mole of thrombospondin 1 trimer binds 3 mol of neutrophil elastase or up to 6 mol of cathepsin G, with site-binding dissociation constants around the nanomolar range, and the enzymes have been shown to interact with thrombospondin 1 in the vicinity of the calcium-binding type 3 repeats. None of the protein modules in this region, or within the whole thrombospondin 1 molecule, have previously been implicated in the inhibition of proteinases. We noted that there are two stretches of eight amino acids each in the human thrombospondin 1 type 3 repeats, residues 735-742 and 794-801, that have striking similarity to a reactive-site consensus sequence derived from selected members of the Kazal and Streptomyces subtilisin inhibitor families. Synthetic peptides corresponding to the putative P5 through P4' residues of both proposed reactive centers interacted efficiently with the active site of cathepsin G and were competitive inhibitors of the fibronectin-degrading and platelet-activating activities of this enzyme, while only the peptide corresponding to residues 793 801 efficiently interacted with the active site of neutrophil elastase and competitively inhibited its fibronectin-degrading activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204589 TI - Contribution of the heavy and light chains of factor Va to the interaction with factor Xa. AB - The interactions of the isolated heavy and light chains of factor Va with factor Xa were evaluated using active-site-modified factor Xa [(carboxytetramethyl)rhodamine-Glu-Gly- Arg-factor Xa (ctr-EGR-Xa)]. The Kd for the factor Va heavy-chain interaction with ctr-EGR-Xa was 60 microM. A series of monoclonal antibodies directed against bovine factor Va were tested for their ability to inhibit thrombin formation in an assay using the fluorescent thrombin inhibitor dansylarginine N,N-(3-ethyl-1,5-pentanediyl)amide (DAPA). Monoclonal antibody alpha BFV-4, which recognizes the light chain of the cofactor, was found to inhibit the formation of thrombin. Similarly, monoclonal antibody alpha BFV-5, which is directed against the heavy chain of the cofactor, was found to inhibit thrombin formation. In contrast, monoclonal antibody alpha BFV-1, also directed against the heavy chain of the cofactor, did not inhibit thrombin generation by the prothrombinase complex. Monoclonal antibodies alpha BFV-4 and alpha BFV-5 inhibited the interaction of active-site-modified radiolabeled factor Xa (125I-Xa EGR) with factor Va bound to PC/PS-coated microtiter wells, whereas nonimmune mouse IgG did not have any effect on the 125I-Xa-EGR.membrane-bound factor Va interaction. The antibodies effect upon the phospholipid-independent interaction between the cofactor and ctr-EGR-Xa was evaluated by analytical ultracentrifugation. Both alpha BFV-4 and alpha BFV-5 inhibited the phospholipid independent interaction between factor Va and ctr-EGR-Xa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204590 TI - Replacement of the proximal ligand of sperm whale myoglobin with free imidazole in the mutant His-93-->Gly. AB - The proximal bond between the iron atom of the heme group and the N epsilon of histidine F8 in myoglobin (Mb) and hemoglobin (Hb) is presumed to be an important determinant of heme binding, protein structure, and oxygen binding. Here a system is described in which the proximal ligand is provided intermolecularly by the histidine side chain mimic imidazole. The proximal ligand of sperm whale Mb is replaced with glycine (H93G) using site-directed mutagenesis. The addition of imidazole to Escherichia coli expressing this gene reconstitutes myoglobin function. H93G Mb purified in the presence of imidazole is spectroscopically similar to wild-type Mb in combination with a wide variety of distal ligands. The crystal structure of H93G Mb, determined in the presence of imidazole, reveals that an imidazole molecule is bonded to the heme iron on the proximal side, substituting in trans for the side-chain function of the proximal histidine of wild-type Mb. Although H93G Mb is similar in spectroscopic and gross structural detail to wild-type Mb, subtle differences exist in the orientation of imidazole with respect to the heme group. trans-Complementation of proximal ligand function will allow the proximal bond in hemoproteins to be chemically substituted beyond the limits of the genetic code. PMID- 8204591 TI - The fibrin(ogen)olytic properties of cathepsin D. AB - Fibrin(ogen) is important for hemostasis and is cleared from sites of vascular injury primarily by the plasminogen activator system. However, there is emerging evidence in plasminogen activator-deficient transgenic mice that non-plasmin pathways may also be important for endogenous fibrinolysis. We have recently described an alternative, plasmin-independent fibrinolytic pathway in activated human monocytes that utilizes the integrin Mac-1 (CD11b/CD18), which directly binds and internalizes fibrin, resulting in its lysosomal degradation. The identity of the lysosomal fibrinolytic enzyme(s) responsible for monocyte/macrophage-mediated fibrinolytic is unknown. Protease inhibitor studies now suggest that an aspartyl protease is responsible for this fibrinolytic activity. We, therefore, examined the fibrinolytic properties of cathepsin D, a lysosomal aspartyl protease, and report that cathepsin D possesses both fibrinogenolytic and fibrinolytic activity. Cathepsin D cleavage of fibrinogen follows Michaelis-Menten kinetics with a Michaelis constant, Km, of 1.5 microM; catalytic rate constant, kcat, of 1.4 x 10(-3) s-1; and catalytic efficiency, kcat/Km, of 9.3 x 10(-4) microM-1 s-1. A pH-activity profile of fibrinogen digestion by cathepsin D demonstrates a pH optimum of 3.5 with 50% residual activity at pH 5.0. Fibrinolysis was assessed by fibrin plate and fibrin clot lysis assays. Cathepsin D possesses significant fibrinolytic activity over a dose range of 100 nM to 10 microM and is able to lyse fibrin, as well as albumin enriched and albumin/red cell-enriched fibrin clots. Cathepsin D cleaves the alpha-, beta-, and gamma-chains of FGN, generating multiple low-molecular-weight fragments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204592 TI - The serine receptor of bacterial chemotaxis exhibits half-site saturation for serine binding. AB - Ligand binding to the serine receptor of Escherichia coli has been studied using isothermal titration calorimetry. Bacterial inner membranes enriched in the serine receptor (Tsr) were titrated as sonicated membrane samples and after solubilization in octyl beta-D-glucopyranoside (OG) to determine the number of moles of ligand bound per mole of receptor (n), the binding constant (Ka), and the enthalpy of binding (delta H) of serine to the receptor. The n value for serine binding to OG-solubilized Tsr protein (n = 0.5) was consistent with one molecule of serine binding to a receptor dimer, but in sonicated inner membrane samples, the n value was smaller (n approximately equal to 0.25), indicating that not all of the binding sites were accessible to added serine. At 7 and 27 degrees C, the values for Ka and delta H were equivalent for the membrane and OG solubilized samples and were found to be 4.7 x 10(4) M-1 and -15 kcal/mol, and 3.6 x 10(4) M-1 and -18 kcal/mol, respectively. The influence of covalent modification at the sites of methylation on the affinity of the receptor for serine was also investigated, and found to have only a modest effect. The property of half-site saturation is suggestive of models for transmembrane signaling where the receptor subunit interactions are modulated by ligand binding. PMID- 8204593 TI - Mutagenic analysis of a receptor contact site on interleukin-2: preparation of an IL-2 analog with increased potency. AB - Interleukin-2 (IL-2) is a 133 amino acid alpha-helical protein secreted by activated T-cells. Combinatorial cassette mutagenesis was used to investigate the functional role of a continuous five amino acid region of IL-2 suspected to interact with the intermediate-affinity IL-2 receptor. A limited random library of IL-2 mutants was constructed in which residues 17-21 (Leu-Leu-Leu-Asp-Leu) were simultaneously mutated. The proteins were produced in an Escherichia coli expression system and screened in a biological assay for their ability to mediate the proliferation of a murine IL-2-dependent cell line. From the over 2600 clones examined, only 42 exhibited significant activity, confirming the functional importance of this region. Selected clones were purified and further characterized by biological and receptor binding assays. Viewed in the context of the recently revised 2.5-A crystal structure for IL-2, these results suggest the following conclusions: both Asp20 and Leu21, as shown by their sensitivity to mutation, are the functionally more important residues in this region, but for different reasons. Asp20 is solvent-accessible and likely plays a direct receptor contact role as previous studies have indicated. Leu21, in contrast, is completely buried in the hydrophobic core of the protein. Substitutions at this position, even a conservative Leu-->Val substitution, were found to perturb the precise hydrophobic packing arrangements that are critical for activity, resulting in a significant loss of function. In addition, one of the analogs identified in the screen was found to be 2-3 times more potent than the wild-type protein. PMID- 8204594 TI - Ethidium bromide intercalation and chromatin structure: a spectropolarimetric analysis. AB - Native chromatin has been characterized at different ionic strengths, according to different methods of preparation, by means of circular dichroism and ethidium bromide intercalation. For a more precise interpretation of these results, a series of analogous experiments on phagic DNA, as a function of its circularization, and on mononucleosomes have been performed. Results are discussed here in terms of high order chromatin structure, DNA supercoiling, and topological constraints. PMID- 8204595 TI - Antibody-induced conformational changes in the Torpedo nicotinic acetylcholine receptor: a fluorescence study. AB - Quantitative fluorescence spectroscopy was used to develop a structural picture of the effects of two monoclonal antibodies (mAbs) on the conformation of the Torpedo nicotinic acetylcholine receptor (nAChR). The two mAbs (A6 and B1) examined selectively blocked ligand binding to either the high-affinity (A) or the low-affinity (B) binding sites for agonists/competitive antagonists. The distances between dansyl-C6-choline bound to the unblocked agonist/competitive antagonist binding site and one of two lipophilic probes (C12-eosin or C18 rhodamine) partitioned into the lipid membrane were estimated by using fluorescence resonance energy transfer. Control experiments demonstrated that both mAbs decreased the affinity and fluorescence lifetime of receptor-bound dansyl-C6-choline. The binding of the B1 mAb to the B site did not significantly change the calculated distance between the unblocked A binding site and the membrane surface. However, the binding of the A6 mAb to the A site induced the B site to move into close proximity to the lipid membrane. This conformational change was confirmed by a 45-fold increase in the paramagnetic quenching of the B site-bound dansyl-C6-choline fluorescence by lipid-intercalated 5-doxylstearate. The results indicate that these mAbs not only selectively block ligand binding to either the A or the B acetylcholine sites but also, in the case of the A6 mAb, induce global conformational changes of the receptor, which appear to involve a movement of the B binding site into close proximity of the lipid membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204596 TI - Structure by NMR of antitumor drugs aclacinomycin A and B complexed to d(CGTACG). AB - Aclacinomycins A and B are anthracycline antibiotics with potent antitumor activity. Each consists of an alkavinone aglycon chromophore and a trisaccharide (rhodosamine-deoxyfucose-cinerulose A or B) tail attached at the C7 of ring A of the alkavinone. The structures of the 2:1 aclacinomycin-d(CGTACG) complexes have been studied in solution by 2D NMR spectroscopy using nuclear Overhauser effect data. SPEDREF refinement procedure (incorporating simulated annealing within the program X-PLOR) was used to obtain an ensemble of refined structures which reveal that the elongated alkavinone is intercalated between the CpG steps and the trisaccharide lies in the minor groove. In the complex, the two GC Watson-Crick base pairs (C1:G12 and G2:C11) that wrap around the aglycon have large buckles, consistent with those seen in the crystal structures of other anthracycline-DNA complexes. The intercalation geometry of aclcainomycin is a hybrid between those of daunorubicin and nogalamycin. Ring D of alkavinone is sandwiched by the C1 and C11 bases. The deoxyfucose ring of the trisaccharide is close to the DNA backbone at the A4 nucleotide, forcing the DNA helix to kink toward the major groove (with the opening in the minor groove). The kink between two adjacent A-T base pairs (T3-A10 and A4-T9) causes the adenine A4N6 to form two hydrogen bonds to T9O4 (interstrand) and T3O4 (intrastrand) simultaneously. There is a small unwinding of the helix resulting from the intercalated aclacinomycin. Several potential hydrogen bonds exist between the drug and the guanine bases in the minor groove of the helix.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204597 TI - Growth factor modulated calmodulin-binding protein stimulates nuclear DNA synthesis in hemopoietic progenitor cells. AB - A specific calmodulin-binding protein of 68 kDa (CaM-BP68) is modulated in response to growth factors that induce proliferative stimulation in a variety of hemopoietic progenitor cells. The nuclear localization of the CaM-BP68 coincided temporally with interleukin 3 (IL-3)-dependent progression of synchronized FDC-P1 cells from G1 to S phase [Reddy et al. (1992) Blood 79, 1946-1956]. To delineate the role of the CaM-BP68 in the onset of DNA synthesis (S phase), this protein was purified to an apparent homogeneity from FDC-P1 cells and its effects on DNA replication in permeabilized FDC-P1 cells were examined. Purified CaM-BP exhibited a single silver-stained protein band of 68 kDa on SDS-polyacrylamide gels. This purified protein, when incubated with permeabilized log-growing FDC-P1 cells, caused a 3-4-fold increase in the rate of [3H]dTTP incorporation into DNA as compared to the controls. There was a direct correlation between the increase in the rate of [3H]dTTP incorporation into DNA and the concentration of the added CaM-BP68 in the incubation mixture. These observations suggest that the CaM-BP68, whose nuclear localization is associated with growth factor dependent proliferative stimulation of myeloid progenitor cells, is involved in the regulation of nuclear DNA synthesis. PMID- 8204598 TI - High-resolution solution structure of reduced parsley plastocyanin. AB - A high-resolution three-dimensional solution structure of parsley plastocyanin has been determined using 1H-NMR-derived data. An ensemble of 30 conformers has been calculated, exhibiting an atomic root mean square distribution about the mean coordinate positions of 0.37 +/- 0.03 A for backbone atoms and 0.75 +/- 0.04 A for all heavy atoms. (These values exclude residues 8-10 which are disordered.) The global fold of parsley plastocyanin is closely similar to those of other plastocyanins which have been structurally characterized by X-ray diffraction and NMR methods. However, deletion of residues at positions 57 and 58 of the consensus plastocyanin sequence causes elimination of a turn found in most higher plant plastocyanins. This turn is located in an acidic patch binding site, which consists of two clusters of acidic residues at positions 42-45 and 59-61. These residues surround the side chain of Tyr 83, which has been shown to be involved in binding of and electron transfer from cytochrome f, one of plastocyanin's physiological partners. The acidic recognition site is further disrupted in parsley plastocyanin by nonconservative substitution of two charged residues at positions 59 and 60. The NMR-derived structures show that E53, E85, and E95 compensate for these substitutions and give parsley plastocyanin an acidic recognition site of similar extent to that of other higher plant plastocyanins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204599 TI - 1H NMR studies of interleukin 8 analogs: characterization of the domains essential for function. AB - 1H NMR studies were carried out on interleukin 8 (IL-8) analogs in order to probe the structural features that are essential for receptor binding and function. The analogs studied were the chemically synthesized IL-8 (1-72), a series of N terminally truncated derivatives (4-72, 5-72, and 6-72), and derivatives with single amino acid substitutions (I10A, R6K, and H33A). Previous functional studies have shown that the N-terminal residues, especially the residues at positions 4-6, and the beta turn containing Cys-34, which is disulfide linked to Cys-7, are important for receptor affinity and functional activity [Clark-Lewis, I., Schumacher, C., Baggiolini, M., & Moser, B. (1991) J. Biol. Chem. 266, 23128 23134; Clark-Lewis, I., Dewald, B., Loetscher, M., Moser, B., & Baggiolini, M. (1994) J. Biol. Chem. (in press)]. The 6-72 and R6K analogs also showed properties of an antagonist. Analysis of the 1H NMR parameters such as chemical shifts, amide proton chemical shift temperature coefficients, and NOESY data indicates that the core structure is the same for all these proteins. Small differences were observed in some of the NMR properties for some of the residues in the N-terminal region and the turn containing Cys-34. Detailed analysis suggests that there is no correlation between these differences and observed function. Thus functional differences between the N-terminal analogs are a direct consequence of changes in receptor binding due to substitutions/deletions in the N-terminal sequence and not due to structural changes elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204600 TI - Proton NMR investigation of substrate-bound heme oxygenase: evidence for electronic and steric contributions to stereoselective heme cleavage. AB - The substrate-bound form of the enzyme heme oxygenase (HO), which catalyzed the stereospecific alpha-meso bridge cleavage of hemin to yield biliverdin IX alpha, has been investigated by 1H NMR in both its primarily high-spin and its cyanide inhibited low-spin forms. Both derivatives yield 1H NMR spectra indicative of extensive heterogeneity that is largely resolved when a 2-fold-symmetric hemin substrate is bound. The structural origin of the heterogeneity is shown to result from approximately 1:1 isomeric binding of the native hemin substrate in the binding pocket. The substrate orientational disorder is about the alpha,gamma meso axis, as established on the basis of 2D NMR experiments that identify characteristic aromatic van der Waals contact in the substrate binding pocket. The isomeric substrate-HO complexes exhibit differential cyanide affinity, and the ratio of isomers is sensitive to the hemin 2,4-substituents. The assignment of hemin signals by isotopic labeling and 2D NMR methods reveals a contact shift pattern that reflects an unusual hemin electronic structure that is characterized by large differences in delocalized spin density for the two positions within a given pyrrole, rather than the more conventional large differences between adjacent pyrroles. This pattern of spin density delocalized primarily to the pyrrole positions adjacent to the alpha,gamma-meso axis can be rationalized by postulating a direct electronic perturbation of the hemin by the protein matrix in the form of an anionic side chain close to the alpha-meso carbon. Similar influences on hemin electronic structure, in the form of chemical substitution of the meso positions, have been observed in iron porphyrin compounds and successfully modeled by simple molecular orbital theory (Tan et al., 1994). This is interpreted as evidence for a direct electronic effect by HO to activate the alpha-meso position for electrophilic rather than nucleophilic attack. The unique contact shift pattern is present to different degrees for the two hemin orientations, is strongly pH dependent, and is largely abolished at acidic pH. Portions of several heme pocket residues are located and it is shown that the pattern of the dipolar shifts for these residues, which likely reflects the distal steric influence on the tilt of the coordinated cyanide, differs significantly for the two substrate orientations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8204601 TI - Structure, synthesis, and activity of dermaseptin b, a novel vertebrate defensive peptide from frog skin: relationship with adenoregulin. AB - A novel antimicrobial peptide, designated dermaseptin b, was isolated from the skin of the arboreal frog Phyllomedusa bicolor. This 27-residue peptide amide is basic, containing 3 lysine residues that punctuate an alternating hydrophobic and hydrophilic sequence. In helix-inducing solvent, dermaseptin b adopts an amphipathic alpha-helical conformation that most closely resembles class L amphipathic helixes, with all lysine residues on the polar face of the helix. The peptide exhibits growth inhibition activity in vitro against a broad spectrum of pathogenic microorganisms including yeast and bacteria as well as various filamentous fungi that are responsible for severe opportunistic infections accompanying acquired immunodeficiency syndrome and the use of immunosuppressive agents. Maximized pairwise sequence alignment of dermaseptin b and dermaseptin s, a 34-residue antimicrobial peptide previously isolated from Phyllomedusa sauvagii, reveals 81% amino acid identity. No other significant similarity was found between dermaseptin b and any prokaryotic or eukaryotic protein, but similarity was found with adenoregulin (38% amino acid postional identity), a 33 residue peptide that enhances binding of agonists to the A1 adenosine receptor. The synthetic replicates of dermaseptin b and adenoregulin displayed similar but nonidentical spectra of antimicrobial activity, and both peptides were devoid of lytic effect on mammalian cells. Accordingly, the observation that adenoregulin enhances binding of agonists to the adenosine receptor may in fact be a consequence of its ability to alter the structure of biological membranes and to produce signal transduction via interactions with the lipid bilayer, bypassing cell surface receptor interactions. PMID- 8204602 TI - Phosphatidyl-L-serine is necessary for protein kinase C's high-affinity interaction with diacylglycerol-containing membranes. AB - The contributions of phospholipid headgroup structure, diacylglycerol, and Ca2+ in regulating the interaction of protein kinase C beta II with membranes or detergent/lipid mixed micelles were examined. Binding measurements revealed that, in the absence of diacylglycerol, protein kinase C displays no significant selectivity for headgroup structure other than change: the enzyme binds with equal affinity to phosphatidyl-L-serine, phosphatidyl-D-serine, and other monoanionic lipids such as phosphatidylglycerol. In contrast, selectivity for headgroup occurs in the presence of diacylglycerol. This second messenger increases the affinity of protein kinase C for phosphatidyl-L-serine-containing membranes or micelles by 2 orders of magnitude, but has only moderate effects on the affinity of protein kinase C for surfaces containing other anionic lipids. Ca2+ does not affect the diacylglycerol-mediated increase in protein kinase C's affinity for phosphatidylserine, but does increase the enzyme's affinity for acidic phospholipids. Lastly, ionic strength studies reveal that electrostatic interactions are the primary driving force in the interaction of protein kinase C with membranes. In the absence of either diacylglycerol or phosphatidylserine, these interactions are sufficiently weak that little binding occurs at physiological ionic strength; thus, protein kinase C is unlikely to translocate to the plasma membranes in the absence of diacylglycerol, even if intracellular Ca2+ levels are high. Our data reveal that, although there is no specificity for binding acidic lipids in the absence of diacylglycerol, specific structural elements of the L-serine headgroup are required for the high-affinity binding of protein kinase C to diacylglycerol-containing membranes. PMID- 8204603 TI - Interaction of bombolitin III with phospholipid monolayers and liposomes and effect on the activity of phospholipase A2. AB - This study is focused on the characterization of the interaction of the amphiphilic peptide bombolitin III (from the bumblebee Megabombus pennsylvanicus) with phospholipid monolayers and vesicles. It is shown that due to the amphiphilic character of its alpha-helical conformation this water-soluble peptide is able to interact in an ordered fashion with phospholipid organized structures. Depending on the temperature, the subphase, and the particular phosphatidylcholine used, the mixed peptide-phospholipid monolayers can be homogeneous or display phase separation. This behavior was observed by means of the Langmuir film balance technique, coupled with an epifluorescence microscope. In well-defined conditions it is possible to visualize the formation of phase separated peptide domains at the air-water interface and to study the effect of their presence on the organization of the lipid. The action of phospholipase A2 at the lipid-peptide interface was also followed by means of fluorescence microscopy: some evidence that the enzyme preferentially hydrolyzes the phospholipid that is in contact with the peptide is presented. Furthermore, the presence of bombolitin III in L-alpha-DLPC monolayers causes an increase in the initial speed of degradation with phospholipase A2. These results are in agreement with previous findings that show that the bombolitins are activators in vitro of phospholipase A2. Experiments were also performed with peptide fragments corresponding to the alpha-helical sequences of the protein uteroglobin: despite some amphiphilic character, these peptides do not interact strongly with phospholipid monolayers. Only one of these peptides (corresponding to the helix 4 14 in uteroglobin) is adsorbed in the monolayer in a similar fashion to bombolitin III but does not cause an increase in the activity of phospholipase A2. PMID- 8204604 TI - Binding and state of aggregation of spin-labeled cecropin AD in phospholipid bilayers: effects of surface charge and fatty acyl chain length. AB - The binding and state of aggregation of cecropin in large unilamellar vesicles of different surface potential and varying acyl chain length were examined using a Cys-33 spin-labeled derivative of cecropin AD (CAD). Association isotherms of the peptide were measured for vesicles of 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphatidylcholine (POPC) containing 5, 15, and 30 mol % 1-palmitoyl-2-oleoyl-sn glycero-3-phosphatidylglycerol (POPG). The isotherms display a concentration dependent positive cooperativity indicating the possible formation of cecropin aggregates in the lipid phase. The critical aqueous concentration for aggregation was dependent on the fraction of POPG, suggesting the involvement of acidic lipids in the formation and stabilization of the putative aggregate. Our data also indicate that cooperativity depends on the state of side-chain ionization of an acidic residue that titrates between pH 7 and 4.4. The binding of spin-labeled Cys-33 CAD was found to be influenced by the acyl chain length of the host lipid. The association isotherm of the peptide for dilaureoyl-sn-glycero-3 phosphatidylcholine vesicles containing 30 mol % dilauroyl-sn-glycero-3 phosphatidylglycerol (DLPG) differed significantly from that in POPC/POPG and could be interpreted in terms of a monomer-monomer partitioning between the aqueous and lipid phases. ESR line-shape analysis was consistent with peptide aggregation in dioleoyl-sn-glycero-3-phosphatidylglycerol vesicles but not in DLPG vesicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204605 TI - A model membrane approach to the epidermal permeability barrier. AB - The permeability barrier of mammalian skin is found in unusual intercellular domains in the upper layers of the epidermis, and is composed mainly of three lipid classes: ceramide, cholesterol, and free fatty acid. These are organized as lamellae, but the details of lipid organization are not precisely known. To examine the relationship between lipid composition and phase behavior, aqueous dispersions of bovine brain ceramide, cholesterol, and perdeuterated palmitic acid were examined by 2H NMR and compared to analogous systems in which sphingomyelin replaced ceramide. The sphingomyelin systems give rise as expected to a stable fluid lamellar signal over the temperature range 20-75 degrees C and pH 5.2-7.4, whereas the ceramide dispersions show complex polymorphism as a function of both temperature and pH. Prominent features of the ceramide dispersions containing cholesterol are phase coexistence and the presence of a "solid" phase in which molecular motion is more inhibited than in a classical phospholipid gel phase: T1z measurements indicate that lateral diffusion of the palmitic acid probe effectively does not occur. In the absence of cholesterol, a fluid lamellar signal is not observed, but the appearance of a "solid" signal is also influenced by the pH. In the presence of cholesterol, a fluid lamellar signal is present at 50 degrees C, and the 2H NMR order parameter profile is very similar to that derived from the analogous sphingomyelin dispersions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204606 TI - Myosin S1 changes the orientation of caldesmon on actin. AB - Changes in the orientation of caldesmon bound to actin in skeletal ghost myofibrils caused by the binding of myosin subfragment 1 (S1) were measured by fluorescence-detected linear dichroism using fluorescence microscopy. Gizzard caldesmon, labeled with acrylodan at its two Cys residues (CaD*), bound to actin with a probe angle that was unaffected by actin-bound tropomyosin. Irrigation of fibrils with myosin S1 dissociated most of the bound CaD*, but reintroduction of CaD* resulted in its rebinding to actin, without dissociation of S1, with a 7 degrees difference in probe angle. A similar change in probe angle was also observed when a 27-kDa actin-binding C-terminal fragment of caldesmon, labeled with acrylodan at its single Cys 580 (CaD-27*), was used. Introducing MgADP, which bound to S1 in the CaD*-actin-S1 ternary complex in the fibril, reversed the bound CaD* dichroism. These results indicate that (i) myosin heads and caldesmon compete for a common actin binding site; (ii) a ternary complex of CaD* actin-S1 can be formed with an orientation of CaD* different from that in the CaD*-actin binary complex, and (iii) MgADP, which binds to and reorients myosin S1, affects the orientation of CaD* in the ternary complex. These results are consistent with a two-state binding model of caldesmon for actin in which state 1 involves a site that is competitive with S1 binding and state 2 involves a site that is formed in the presence of bound S1. PMID- 8204607 TI - Pore-forming peptides induce rapid phospholipid flip-flop in membranes. AB - A kinetic model for pore-mediated and perturbation-mediated flip-flop is presented and used to characterize the mechanism of peptide-induced phospholipid flip-flop in bilayers. The model assumes that certain peptides can bind to and aggregate within the membrane. When the aggregate attains a critical size (M peptides), a channel is created that results in a fast flip-flop of phospholipids. In addition, certain peptides induce flip-flop through perturbation of the membrane without forming a pore. Donor phospholipid vesicles with an asymmetrical distribution of the fluorescent phospholipid 1-oleoyl-2-[12 [(7-nitro-1,2,3-benzoxadiazol-4- yl)amino]dodecanoyl]phosphatidylcholine (NBD-PC) were used to measure the extent of flip-flop by quantitating the decrease in fluorescence as the NBD-PC exchanged from the donor vesicles to acceptor vesicles that contained a quencher of the NBD fluorescence. Flip-flop curves generated at lipid/peptide ratios ranging from 30/1 to 300000/1 could be well-simulated by the model. Pore-forming peptides, such as melittin or the synthetic peptide GALA (WEAALAEALAEALAEHLAEALAEALEALAA), induce rapid phospholipid flip-flop with half times for flip-flop of seconds at low peptide/vesicle ratios. The deduced pore sizes are M = 10 +/- 2 for GALA and M = 2 - 4 for melittin. The synthetic peptide LAGA (WEAALAEAEALALAEHEALALAEAELALAA) can catalyze flip-flop via bilayer perturbation. In contrast, hydrophobic peptides such as gramicidin A and valinomycin intercalate into the membrane, but induce little flip-flop. Modeling of the kinetics of phospholipid translocation supports pore formation as the key factor in accelerating phospholipid flip-flop. Thus, amphipathic segments from membrane proteins may account for non-energy-dependent phospholipid flip-flop in biological membranes. PMID- 8204608 TI - Purification and characterization of the recombinant human calcium-binding S100 proteins CAPL and CACY. AB - The S100 proteins CAPL and CACY are expressed in a tissue- and cell-specific manner and have been reported to be associated with the metastatic phenotype of tumor cells. In order to study the biochemical, cation-binding, and conformational properties, we produced and purified large amounts of the recombinant human proteins in Escherichia coli. Several characteristics of native proteins are shown to correspond to those of the bacterially expressed proteins. Both are able to form homodimers in vitro, probably the biologically active species, but not heterodimers. The Ca(2+)-binding parameters were studied by flow offlysis at physiological ionic strength. Both isotherms show a maximum of two Ca2+ per protein and are insensitive to Mg2+, indicating that the sites are of the Ca(2+)-specific type. The isotherms show slight (CAPL, nH = 1.15) or pronounced (CACY, nH = 1.33) positive cooperativity with K0.5 values of 0.32 mM (CACY) and 0.15 mM (CAPL), indicating that the sites are of the low-affinity type. Conformational changes in the Tyr microenvironment of CACY indicate that Ca2+ binding induces a shift of Tyr to a less polar environment. Mg2+ does not affect the fluorescence properties nor does it induce a difference spectrum, thus suggesting that at physiological ionic conditions it does not interact with the protein. The Ca(2+)-induced difference spectra of CAPL are about 3 times smaller than those of CACY, suggesting that the additional Tyr84 in CACY is much more sensitive to Ca2+ than the two Tyr residues conserved in both proteins. PMID- 8204609 TI - Structural mechanisms for domain movements in proteins. AB - We survey all the known instances of domain movements in proteins for which there is crystallographic evidence for the movement. We explain these domain movements in terms of the repertoire of low-energy conformation changes that are known to occur in proteins. We first describe the basic elements of this repertoire, hinge and shear motions, and then show how the elements of the repertoire can be combined to produce domain movements. We emphasize that the elements used in particular proteins are determined mainly by the structure of the interfaces between the domains. PMID- 8204610 TI - Coherent dynamics during the primary electron-transfer reaction in membrane-bound reaction centers of Rhodobacter sphaeroides. AB - The temporal evolution of the near-infrared stimulated emission band of the special pair excited state (P*) in the reaction center of Rhodobacter sphaeroides has been studied in intracytoplasmic membranes of the antenna-deficient RCO1 mutant at 10 K with a resolution of 30 fs. On the 100-fs time scale the emission band gradually shifts to longer wavelengths. After 150 fs the band shifts back to shorter wavelengths and continues to develop on the picosecond time scale in a damped oscillatory manner (most prominent fundamental frequencies around 15 cm-1 and at 92, 122, and 153 cm-1). These phenomena are shown to be due to low frequency vibrational motions in the P* excited state that conserve their phase on the time scale of electron transfer. These results imply that the vibrational manifold of P* is not thermalized during the electron-transfer reaction in functional reaction centers. The initial Stokes shift dynamics are largely determined by the modes in the 90-160-cm-1 frequency range, which probably involve motions of several chromophores, including the bacteriopheophytin electron acceptor HL. PMID- 8204611 TI - Crystallographic structure of a phosphonate derivative of the Enterobacter cloacae P99 cephalosporinase: mechanistic interpretation of a beta-lactamase transition-state analog. AB - The crystal structure of a complex formed on reaction of the Enterobacter cloacae P99 cephalosporinase (beta-lactamase) with a phosphonate monoester inhibitor, m carboxyphenyl [[N-[(p-iodophenyl)acetyl]amino]methyl]phosphonate, has been obtained at 2.3-A resolution. The structure shows that the inhibitor has phosphonylated the active site serine (Ser64) with loss of the m-carboxyphenol leaving group. The inhibitor is positioned in the active site in a way that can be interpreted in terms of a transition-state analog. The arylacetamido side chain is placed as anticipated from analogous beta-lactamoyl complexes of penicillin-recognizing enzymes, with the amino group hydrogen-bonded to the backbone carbonyl of Ser318 (of the B3 beta-strand) and to the amides of Gln120 and Asn152. There is support in the asymmetry of the hydrogen bonding of this side chain to the protein and in the 2-fold disorder of the benzyl group for the considerable breadth in substrate specificity exhibited by class C beta lactamases. One phosphonyl oxygen atom is in the oxyanion hole, hydrogen-bonded to main-chain NH groups of Ser318 and Ser64, while the other oxygen is solvated, not within hydrogen-bonding distance of any amino acid side chain. The closest active site functional group to the solvated oxygen atom is the Tyr150 hydroxyl group (3.4A); Lys67 and Lys315 are quite distant (4.3 and 5.7 A, respectively). Rather, Tyr150 and Lys67 are more closely associated with Ser64O gamma (2.9 and 3.3 A). This arrangement is interpreted in terms of the transition state for breakdown of the tetrahedral intermediate in the deacylation step of catalysis, where the Tyr150 phenol seems the most likely general acid. Thus, Tyr150, as the phenoxide anion, would be the general base catalyst in acylation, as proposed by Oefner et al. [Nature (1990) 343, 284-288]. The structure is compared with that of a similar phosphonate derivative of a class A beta-lactamase [Chen et al. (1993) J. Mol. Biol. 234, 165-178], and mechanistic comparisons are made. The sensitivity of serine beta-lactamases, as opposed to serine proteinases, toward inhibition by phosphonate monoanions is supported by electrostatic calculations showing a net positive potential only in the catalytic sites of the beta lactamases. PMID- 8204612 TI - Two-dimensional transferred nuclear Overhauser effect spectroscopy study of the confirmation of MgATP bound at the active and ancillary sites of rabbit muscle pyruvate kinase. AB - Pyruvate kinase binds one adenosine 5'-triphosphate (ATP) molecule at its active site and another at an ancillary site on each subunit. In order to determine the conformation of ATP bound at these sites, proton transferred two-dimensional nuclear Overhauser effect spectroscopy (TRNOESY) measurements were made at 500 MHz and 10 degrees C for several mixing times in the range 40-200 ms. The NOE values for the proton pair H1'-H2' of ribose (which are 2.9 +/- 0.2 A apart, irrespective of nucleotide conformation) as a function of ligand concentration (1 10 mM ATP), with the ratio of ligand to enzyme being kept constant, indicate that at higher ligand concentrations adventitious binding of ATP at nonspecific site(s) makes a major contribution to the observed NOEs. When the ligand concentration is < 2 mM, site-specific NOEs can be measured. Furthermore, addition of phosphoenolpyruvate (PEP) to the enzyme-MgATP sample results in competitive displacement of MgATP from the active site and reduces the observed NOE to that arising exclusively at the ancillary site, thus allowing the measurement of site-specific NOEs. The interproton distances determined from such site-specific NOE buildup curves were used as constraints in CHARMm to obtain the structure of MgATP. At the active site, MgATP has a glycosidic torsion chi = 44 +/- 5 degrees and the phase angle of pseudorotation for ribose P = 42.4 degrees. At the ancillary site chi = 46 +/- 5 degrees and P = 127.6 degrees. Thus the orientation of the adenine with respect to the sugar moiety is the same at both sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204613 TI - C-terminal secretion signal of an Erwinia chrysanthemi protease secreted by a signal peptide-independent pathway: proton NMR and CD conformational studies in membrane-mimetic environments. AB - The detailed structure of a 68-residue chimeric peptide encompassing the 56 last C-terminal residues of Erwinia chrysanthemi protease G has been investigated by using circular dichroism and NMR spectroscopies. The peptide which contains the secretion signal of PrtG was solubilized either in aqueous solvent, in trifluoroethanol (TFE)/H2O mixtures, or in dodecyl beta-D-maltoside detergent. The peptide helical content increases upon TFE and detergent additions. A stable conformation is reached at 40% TFE (v:v) and at a micelle to peptide ratio higher than 1. The 1H NMR spectrum has been assigned in TFE/H2O, 2:1 (v:v), and it is shown that residues 26-29 and 50-62 form a relatively stable helix although a conformational equilibrium between a helix and probably a more random structure is observed throughout fragment 13-63. Comparison of the CterG conformation with results obtained by deletion approach could lead to the hypothesis that the C terminal secretion signal is composed of an alpha-helix located close to the essential C-terminal tetrapeptide D65VIV. PMID- 8204614 TI - A determination of the solution conformation of the nonmammalian tachykinin eledoisin by NMR and CD spectroscopy. AB - The nonmammalian tachykinin eledoisin was investigated by use of CD and two dimensional NMR techniques. In aqueous solution the peptide is conformationally averaged, but on addition of 50% trifluoroethanol (TFE) or sodium dodecyl sulfate (SDS) it adopts an alpha-helical structure. In TFE/H2O and SDS, residues 6-10 of eledoisin show more conformational order than the terminal regions, which undergo dynamic fraying. A possible turn in the N-terminal "address" region, the putative receptor recognition site of the peptide, is detected by NMR spectroscopy but appears to undergo substantial conformational averaging. The NMR data indicate that the helical central core of eledoisin is better defined in the micellar environment than in TFE; however, partial unfolding via 3(10) intermediates occurs in both cases. The conformational preference for SDS-bound eledoisin was examined by three-dimensional structure calculations using NMR-derived distance information in simulated annealing calculations. PMID- 8204615 TI - Time-resolved solid-state NMR spectroscopy of 5-enolpyruvylshikimate-3-phosphate synthase. AB - The novel technique of time-resolved solid-state NMR spectroscopy has been used to characterize the enzyme, 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase, in both the forward and reverse directions over time periods ranging from 5 to 300 ms. The wealth of data currently available for EPSP synthase, in particular the pre-steady-state kinetics performed using chemical quench-flow experiments [Anderson, K. S., Sikorski, J. A., & Johnson, K. A. (1988) Biochemistry 27, 7395 7406], has made the enzyme an obvious choice as a proving ground for this new technique. Pre-steady-state 13C TOSS CP-MAS spectra have been obtained with a much improved signal-to-noise ratio, and corrections have been made to some previously reported assignments [Evans, J.N.S., Appleyard, R.J., & Shuttleworth, W.A. (1993) J. Am. Chem. Soc. 115, 1588-1590]. Peak fitting has allowed the extrapolation of NMR integral intensities of species involved in the reaction. These show a good correlation with concentrations calculated by simulations using the kinetic parameters obtained from the chemical quench-flow experiments. It is proposed that careful optimization of the contact time used will be necessary to obtain accurate, relative concentrations that will enable an independent kinetic simulation by time-resolved solid-state NMR. The technique shows much promise due to its nondestructive quenching procedure, which allows the direct observation of enzyme intermediates on a reaction pathway. However, its requirement of significantly larger amounts of enzyme does limit the technique to those proteins which naturally occur in high abundance or have been hyperexpressed. PMID- 8204616 TI - Intermediate channeling between ATP sulfurylase and adenosine 5'-phosphosulfate kinase from rat chondrosarcoma. AB - Biosynthesis of the activated sulfate donor PAPS (3'-phosphoadenosine 5' phosphosulfate) involves the sequential action of two enzyme activities. ATP sulfurylase catalyzes the formation of APS (adenosine 5'-phosphosulfate) from ATP and free sulfate, and APS is then phosphorylated by APS kinase to produce PAPS. Using rat chondrosarcoma ATP sulfurylase and APS kinase, a newly developed assay system, which permits measuring the accumulation of both APS and PAPS in the presence of both enzyme activities, produces a PAPS/APS ratio corresponding to a "channeling efficiency" of 96%. The velocity of the APS kinase reaction measured in the overall system with endogenously synthesized APS is 8-fold greater than that of the isolated kinase reaction using exogenous APS. Most conclusively, isotope dilution and enrichment experiments show that the APS intermediate does not equilibrate with APS in the bulk medium but remains largely bound in the rat enzyme system. In contrast, control experiments with a nonchanneled system containing a mixture of the sulfurylase and kinase isolated from Penicillium chrysogenum give the results expected for a nonchanneled pathway. These data indicate that APS is channeled between the active sites of ATP sulfurylase and APS kinase during the production of PAPS in rat chondrosarcoma. PMID- 8204617 TI - The thermodynamics of formation of a three-strand, DNA three-way junction complex. AB - Isothermal titration calorimetry (ITC) is used to study the thermodynamics of assembly of the three DNA oligonucleotides S1 (5'-GCCTGCCACCGC), S2 (5' GCGGTGCGTCCG), and S3AA (5'-CGGACGAAGCAGGC) to form a three-way junction (TWJ) complex consisting of three double-helical arms radiating from a junction region having two unpaired adenosines in one strand (S3AA). The thermodynamics of assembly were measured for three different orders of addition of the component oligonucleotides at four temperatures between 10 and 25 degrees C. At each temperature studied, the overall values of delta H, delta S degrees, and delta G degrees for assembly of the complex from the component single strands were found to be independent of the order of addition. The enthalpy of binding, delta H, was found to be linearly dependent on temperature. From the temperature dependence of delta H, the change in heat capacity delta Cp, for the overall assembly of three strands to form the junction complex was calculated and found to be -1.6 kcal mol 1K-1. This work represents the first attempt to evaluate the thermodynamics of DNA TWJ formation by ITC. PMID- 8204618 TI - Purification and characterization of three inhibitors of voltage-dependent K+ channels from Leiurus quinquestriatus var. hebraeus venom. AB - Three new toxins from the venom of the scorpion Leiurus quinquestriatus var. hebraeus have been identified on the basis of their ability to block the Shaker K+ channel. These toxins have been purified using HPLC techniques and characterized as 38 amino acid peptides by mass spectroscopy, amino acid analysis, and sequence determination. Their chemical identity was confirmed by producing fully functional synthetic toxins using recombinant methods. These peptides are potent inhibitors of the Shaker K+ channel (Kd < 1 nM) as well as the mammalian homologues of Shaker. They are related to other previously described K+ channel toxins, but form a new subclass within the larger family of K+ channel inhibitors derived from scorpion venom. We have named these toxins agitoxin 1, 2, and 3, respectively. PMID- 8204619 TI - Electrostatic potential of the acetylcholine binding sites in the nicotinic receptor probed by reactions of binding-site cysteines with charged methanethiosulfonates. AB - All of the potent agonists and competitive antagonists of the acetylcholine receptors are positively charged, onium compounds. Among the interactions involved in the binding of these compounds, electrostatic forces undoubtedly make an important contribution. There is evidence that the acetylcholine binding site contains both acidic and aromatic amino acids. The acidic side chains could provide long-range charge-charge interactions with acetylcholine, while the aromatic side chains could provide short-range cation-pi-electron and hydrophobic interactions. To probe the long-range electrostatic interactions in the binding site, the rate constants for the reactions of sulfhydryl-specific reagents with cysteines in the binding site have been determined as a function of ionic strength. The reagents are the positively charged methanethiosulfonate ethylammonium and methanethiosulfonate ethyltrimethylammonium, the negatively charged methanethiosulfonate ethylsulfonate, and the neutral methyl methanethiosulfonate. In addition, the rate constants of the reactions of these methanethiosulfonates with positively charged, negatively charged, and uncharged simple thiol compounds have been similarly determined. An analysis of these rate constants in terms of absolute rate theory and Debye-Huckel theory is consistent with the acetylcholine binding site containing two to three negative charges and an electrostatic potential at zero ionic strength of about -80 mV relative to bulk solution. PMID- 8204620 TI - Dual calcium ion regulation of calcineurin by calmodulin and calcineurin B. AB - The dependence of calcineurin on Ca2+ for activity is the result of the concerted action of calmodulin, which increases the turnover rate of the enzyme and modulates its response to Ca2+ transients, and of calcineurin B, which decreases the Km of the enzyme for its substrate. The calmodulin-stimulated protein phosphatase calcineurin is under the control of two functionally distinct, but structurally similar, Ca(2+)-regulated proteins, calmodulin and calcineurin B. The Ca(2+)-dependent activation of calcineurin by calmodulin is highly cooperative (Hill coefficient of 2.8-3), and the concentration of Ca2+ needed for half-maximum activation decreases from 1.3 to 0.6 microM when the concentration of calmodulin is increased from 0.03 to 20 microM. Conversely, the affinity of calmodulin for Ca2+ is increased by more than 2 orders of magnitude in the presence of a peptide corresponding to the calmodulin-binding domain of calcineurin A. Calmodulin increases the Vmax without changing the Km value of the enzyme. Unlike calmodulin, calcineurin B interacts with calcineurin A in the presence of EGTA, and Ca2+ binding to calcineurin B stimulates native calcineurin up to only 10% of the maximum activity achieved with calmodulin. The Ca(2+) dependent activation of a proteolyzed derivative of calcineurin, calcineurin-45, which lacks the regulatory domain, was used to study the role of calcineurin B. Removal of the regulatory domain increases the Vmax of calcineurin, as does binding of calmodulin, but it also increases the affinity of calcineurin for Ca2+. Ca2+ binding to calcineurin B decreases the Km value of calcineurin without changing its Vmax.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204621 TI - Effect of nucleotides and actin on the intramolecular cross-linking of myosin subfragment-1. AB - The heavy chain of myosin subfragment-1 (S1) is cleaved by limited trypsinolysis into three fragments, 27, 50, and 20 kDa--aligned in this order from the N terminus. The tertiary structure of the molecule is essentially not affected by trypsinolysis. The spatial relations between the various regions of the molecule and the nucleotide- and actin-induced intramolecular movements were studied by cross-linking tryptic S1 with N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline (EEDQ), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC), phenylenediglyoxal (PDG), and glutaraldehyde. The formation of cross-linked products was monitored by SDS-PAGE, using the fluorescent probes 9-anthronitrile and N-(iodoacetyl)-N' (5-sulfo-1-naphthyl)ethylenediamine (IAEDANS), which specifically label the 27- and 20-kDa fragments, respectively. The reaction with the cross-linkers leads to the formation of 50-kDa/20-kDa, 27-kDa/20-kDa, 27-kDa/50-kDa, and 20-kDa/light chain cross-linked products. Of these, the most intensive was the formation of the 50-kDa/20-kDa products, which appeared as a doublet on the SDS-PAGE with all the cross-linkers. This indicates that the interface between the two fragments is rather extended. The presence of MgATP or MgADP promoted the formation of the 20 kDa/50-kDa cross-linked products, especially with the lower electrophoretic mobility band, when EEDQ was used as a cross-linker. With PDG as a cross-linker, MgATP also affected the cross-link formation between the 20-kDa fragment and the light chains whereas it had no influence on the formation of other products. On the other hand, the effect of actin on the cross-linking with the various cross linkers was quite extensive, and it was manifested in the reduction of cross-link formation between the various S1 domains. It is concluded that both nucleotides and actin induce intramolecular movements in S1 and that the nucleotide-induced movements are more restricted than those induced by actin, which extend to larger regions of the molecule. PMID- 8204622 TI - Subtype-specific binding of azidoanilido-GTP by purified G protein alpha subunits. AB - Azidoanilido-GTP (AA-GTP), a hydrolysis-resistant, photoreactive GTP analog, is becoming an increasingly popular tool for identifying activation of specific G proteins by receptors within native plasma membranes. Despite the use of AA-GTP as an affinity probe, surprisingly little is known regarding the ability of various G protein alpha subunits to bind this analog. To directly address this issue, we compared the ability of four purified G protein alpha subunits (Go, Gi2, Gs, and Gz) to bind AA-GTP with their ability to bind GTP gamma S, a GTP analog commonly used to characterize the GTP-binding properties of G proteins. All four G alpha subunits tested bound AA-GTP in a manner distinct from their binding of GTP gamma S. One of these proteins, Gs alpha, required millimolar levels of free Mg2+ for significant binding of AA-GTP, while Go alpha and Gi alpha 2 displayed peak AA-GTP binding at approximately 100 microM free Mg2+. The fourth G alpha subunit, Gz, bound AA-GTP very poorly relative to GTP gamma S regardless of the magnesium concentration. These results indicate that individual G protein alpha subunits differ markedly in their ability to bind AA-GTP. Use of AA-GTP to identify specific G protein-receptor interactions must therefore take into account the varied abilities of G alpha subunits to bind this analog. PMID- 8204623 TI - Roles of aspartic acid 15 and 21 in glucagon action: receptor anchor and surrogates for aspartic acid 9. AB - The discovery of aspartic acid at position 9 in glucagon to be a critical residue for transduction has spurred renewed efforts to identify other strategic residues in the peptide sequence that dictate either receptor binding or biological activity. It also became apparent from further studies that Asp9 operates in conjunction with His1 in the activation mechanism that follows binding to the glucagon receptor. Indeed, it was later demonstrated that the protonatable histidine imidazole is important for transduction. It is likely that the interaction of a positively charged histidine 1 with a negatively charged aspartic acid 9 might be part of the triggering step at the molecular level. Two other aspartic acid residues in glucagon are capable of assuming a similar role, namely that of contributing to an electrostatic attraction with histidine via a negative carboxylate. These studies were conducted to investigate the role of aspartic acid 15 and 21 in glucagon action. Evidence reported here, gathered from 31 replacement analogs, supports the idea that in the absence of the requisite carboxyl group at position 9, histidine utilizes Asp21 or Asp15 as a compensatory site. Asp15 was also found to be indispensable for binding and may serve to tether the hormone to the receptor protein at the binding site. It is also demonstrated that these new findings promote the design of better glucagon antagonists. PMID- 8204624 TI - Sequence and structure of the membrane-associated peptide of glycophorin A. AB - Glycophorin A (GPA) has been reconstituted into dimyristoylphosphatidylcholine vesicles and digested with proteinase K to identify the membrane domain and to characterize its structure and orientation. After digestion of the inner and outer domain of GPA by protease action restricted to the aqueous phase, a protected peptide migrates on an electrophoresis gel as a 7.5-kDa dimer (His66 Ile95). The secondary structure and orientation in a lipid bilayer of the 7.5-kDa dimer have been studied by Fourier transform infrared spectroscopy. Our proteolytic and spectroscopic data are in agreement with a topological model in which the His66-Glu72 peptide adopts a beta-sheet conformation and is oriented parallel to the lipid-water interface and the Ile73-Ile95 domain is helical and oriented parallel to the lipid acyl chains, in a transmembrane configuration. Digestion of the domain protruding to the outside of the liposome generates "head head" and "head-tail" dimers of 16 and 38 kDa, respectively. This observation is discussed in terms of the specificity of the dimer formation process. PMID- 8204625 TI - Purification and characterization of colicin V from Escherichia coli culture supernatants. AB - The peptide antibiotic, colicin V (ColV), has been purified and characterized from Escherichia coli culture supernatants by precipitation with trichloroacetic acid (TCA) and high-performance liquid chromatography (HPLC). Polyacrylamide gel electrophoresis (PAGE) and Western analysis identifies ColV as a polypeptide with an apparent molecular mass of 5.8 kDa. The protein identified remains biologically active after purification and SDS-PAGE. A mutant form of ColV, ColV 1, removes the carboxy-terminal 21 amino acids and replaces them with eight heterologous residues. The ColV-1 mutant is also secreted into the extracellular medium, demonstrating that the carboxy-terminal 21 amino acids are not required for secretion by the dedicated ColV export system, CvaAB/TolC. N-Terminal amino acid sequencing shows that the primary translation product of cvaC, the ColV structural gene, is processed to remove the N-terminal 15 amino acids. The cleavage site is preceded by the sequence Ser-Gly-Gly, making it a potential substrate for leader peptidase. The ColV leader sequence has many characteristics in common with the amino-terminal leader sequences of the lactococcins, lactacins, and pediocins from Gram-positive bacteria. Mass spectroscopy of purified ColV shows that it has a mass of 8741.0 amu, consistent with the mass of the unmodified 88 amino acid polypeptide. The purification scheme provides a rapid and simple way to obtain ColV for further biochemical analysis. PMID- 8204626 TI - Kinetic mechanism of cytochrome c folding: involvement of the heme and its ligands. AB - The covalently attached heme and its axial ligands not only are essential for the structure and function of cytochrome c but they also play an important role in the folding process. Under typical denaturing conditions (concentrated guanidine hydrochloride or urea near pH 7), one of the axial ligands, His 18, remains bound to the oxidized heme iron, but the second ligand, Met 80, is replaced by a non native histidine ligand (His 26 or His 33 in horse cytochrome c). Using quenched flow and NMR methods, hydrogen exchange rates were measured for several individual amide protons in guanidine-denatured horse cytochrome c. The observation of a single highly protected (140-fold) backbone amide, that of His 18, suggests the presence of a persistent H-bond consistent with heme ligation of the His 18 side chain in the unfolded state. Heme absorbance changes induced by rapid acidification of oxidized cytochrome c in 4.5 M guanidine hydrochloride from pH 7.8 to 4.6 or below exhibit two kinetic phases with rates of 110 and 25 s 1, attributed to the dissociation of non-native histidine ligands from the heme in the unfolded state. The kinetics of folding from guanidine-denatured cytochrome c under a variety of initial and final conditions was investigated by stopped-flow methods, using tryptophan fluorescence as a conformational probe and Soret absorbance as a probe for the ligation state of the heme. A fast kinetic phase (80 s-1) accompanied by a major decrease in fluorescence and a minor absorbance change coincides with the formation of a partially folded intermediate with interacting chain termini detected in earlier pulsed NH exchange measurements [Roder, H., Elove, G. A., & Englander, S. W. (1988) Nature 335, 700]. At neutral pH, an intermediate kinetic phase (1.8 s-1) accounts for 78% of the absorbance change and 47% of the fluorescence change. In contrast, the folding kinetics at pH 5 is dominated by the fast phase, and the amplitude of the intermediate phase is reduced to approximately 10%. The pH-dependent amplitude changes show titration behavior with an apparent pK of approximately 5.7, consistent with the protonation of a single histidine residue. The intermediate phase can also be suppressed by the addition of 20 mM imidazole. Since both of these conditions interfere with histidine ligation, the intermediate kinetic phase is attributed to the presence of a non-native histidine ligand (His 26 or His 33) that can become trapped in a partially folded intermediate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8204627 TI - Broad spectrum aminoglycoside phosphotransferase type III from Enterococcus: overexpression, purification, and substrate specificity. AB - The aminoglycoside phosphotransferases (APHs) are responsible for the bacterial inactivation of many clinically useful aminoglycoside antibiotics. We report the characterization of an enterococcal enzyme, APH(3')-IIIa, which inactivates a broad spectrum of aminoglycosides by ATP-dependent O-phosphorylation. Overproduction of APH(3')-IIIa has permitted the isolation of 30-40 mg of pure protein/(L of cell culture). Purified APH(3')-IIIa is a mixture of monomer and dimer which is slowly converted to dimer only over time. Dimer could be dissociated into monomer by incubation with 2-mercaptoethanol, suggesting that dimerization is mediated by formation of disulfide bond(s). Both monomer and dimer show Km values in the low micromolar range for good substrates such as kanamycin and neomycin, and kcat values of 1-4 s-1. All aminoglycosides show substrate inhibition except amikacin and kanamycin B. Determination of minimum inhibitory concentrations indicates a positive correlation between antibiotic activity and kcat/Km, but not with Km or kcat. NMR analysis of phosphorylated kanamycin A has directly demonstrated regiospecific phosphoryl transfer to the 3' hydroxyl of the 6-aminohexose ring of the antibiotic. Analysis of structure activity relationships with a variety of aminoglycosides has revealed that the deoxystreptamine aminocyclitol ring plays a critical role in substrate binding. This information will form the basis for future design of inhibitors of APH(3') IIIa. PMID- 8204628 TI - Membrane topology of liver microsomal cytochrome P450 2B4 determined via monoclonal antibodies directed to the halt-transfer signal. AB - The membrane topology of cytochrome P450 2B4 from the endoplasmic reticulum has been studied with highly-purified liver microsomes in a site-directed immunochemical approach. Microsomes were prepared from phenobarbital-induced rabbits, and the resulting microsomal fraction was washed 6 additional times with 0.1 M pyrophosphate buffer to effect removal of significant quantities of adventitiously-bound protein. Monoclonal antibodies were prepared against residues 18-29 of P450 2B4 (Leu18-Leu-Phe-Arg-Gly-His-Pro-Lys-Ala-His-Gly-Arg29), essentially corresponding to the halt-transfer signal. This region was chosen due to its mutually-exclusive location in the two alternative membrane topology models currently tenable [Black, S.D. (1992) FASEB J.6, 680-685]. Model "A" contains a single transmembrane anchor peptide with the amino terminus projecting into the lumen of the endoplasmic reticulum, while model "B" exhibits a hairpin loop of the first approximately 46 residues inserted into the membrane with the amino terminus located on the cytosolic side of the lipid bilayer; the halt transfer signal peptide would be located at the cytosolic surface of the membrane in model "A" or as a loop on the lumenal side of the membrane in model "B". Nine antibodies, denoted as MmAbA, MmAbC, MmAbD, MmAbF, MmAbH, MmAbI, MmAbK, MmAbL, and MmAbP, were produced, and all were identified as IgM/kappa subtypes. Western blotting demonstrated that the antibodies could readily recognize P450 2B4 in microsomes. ELISA assays showed that all of the antibodies exhibited strong binding to intact microsomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204629 TI - Posttranslational sulfation of factor V is required for efficient thrombin cleavage and activation and for full procoagulant activity. AB - Factor VIII and factor V function as cofactors in the blood coagulation cascade to accelerate the rate of activation of factor X and prothrombin, respectively. Both cofactors require proteolytic activation by either activated factor X or thrombin for functional activity. Human factor VIII and factor V expressed in mammalian cells are both modified by posttranslational sulfation of tyrosine residues. In the present study, the posttranslational addition of sulfate in factor V expressed in transfected Chinese hamster ovary (CHO) cells was demonstrated by [35S]sulfate incorporation into the thrombin-cleaved 94-kDa heavy chain and the 150-kDa activation peptide. The presence of tyrosine sulfate in recombinant factor V was confirmed by barium hydroxide hydrolysis and two dimensional thin-layer electrophoresis. The importance of sulfation for factor V secretion and activity was evaluated by characterizing factor V expressed in Chinese hamster ovary cells grown in the presence of sodium chlorate, a potent inhibitor of posttranslational sulfation in intact cells. Increasing concentrations of sodium chlorate inhibited the incorporation of [35S]sulfate into factor V but did not inhibit the synthesis or secretion of factor V. However, the specific activity of factor V secreted in the presence of sodium chlorate was reduced 5-fold. The reduced activity was attributed to (1) slower cleavage and activation by thrombin and (2) a reduced intrinsic activity of factor Va. In contrast, sulfation of factor V did not affect the rate of activation mediated by factor Xa. These results show that sulfation of factor V is required for efficient thrombin activation but not for activation by factor Xa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204630 TI - Deamidation of triosephosphate isomerase in reverse micelles: effects of water on catalysis and molecular wear and tear. AB - The specific deamidation of asparagine-71 of triosephosphate isomerase increases upon substrate binding and catalysis. This deamidation at the dimer interface initiates subunit dissociation, unfolding, and protein degradation. The apparent connection between catalysis and terminal marking supports the concept of "molecular wear and tear", and raises questions related to the molecular events that lead to deamidation. In order to explore this interaction, triosephosphate isomerase was entrapped in reverse micelles with different water contents that support different catalytic rates. Deamidation was quantified for the free enzyme, the enzyme in the presence of substrates, and the enzyme which had been covalently modified at the catalytic center with the substrate analogue 3 chloroacetol phosphate (CAP). Both in water and in reverse micelles of cetyltrimethylammonium with 3% and 6% water, substrate binding enhanced deamidation. Studies of the extent of deamidation at various water concentrations showed that deamidation per catalytic turnover was about 6 and 17 times higher in 6% and 3% water than in 100% water, respectively. The enzyme was also entrapped in micelles formed with toluene, phospholipids, and Triton X-100 to explore the process at much lower water concentrations (e.g., 0.3%). Under these conditions, catalysis was very low, and hardly any deamidation took place. Deamidation of the CAP-labeled enzyme was also markedly diminished. At these low-water conditions, the enzyme exhibited markedly increased thermostability and resistance to hydrolysis of the amide bonds. The data suggest that the rate of deamidation not only is dependent on the number of catalytic events but also is related to the time that asparagine-71 exists in a conformation or solvent environment more favorable for deamidation. PMID- 8204631 TI - Secondary structure and membrane localization of synthetic segments and a truncated form of the IsK (minK) protein. AB - IsK, also referred to as minK, is a membrane protein consisting of 130 amino acids and localized mainly in epithelial cells but also in human T lymphocytes. Depending on the cRNA concentration that was injected into Xenopus oocytes, IsK and its truncated forms can induce either a K+ current alone or both K+ and Cl- currents [Attali et al. (1993) Nature 365, 850-852]. To obtain information on the secondary structure and the topology of IsK in a membrane-bound state, the synthesis, fluorescent-labeling, and structural and functional characterization of five polypeptides of 20-63 amino acids within the rat IsK protein were examined. The alpha-helical content of the segments, assessed in methanol using circular dichroism, suggests that both the N-terminal and transmembrane segments of IsK adopt alpha-helical structures. Binding experiments and the blue shift of 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-labeled peptides suggest that while both the alpha-helical transmembrane segment and the N-terminal of IsK are located within the lipid bilayer, the linking segment between the two segments lies on the surface of the membrane. The fluorescence energy transfer, between donor and acceptor-labeled truncated IsK, suggests that it aggregates within phospholipid membranes. Although a protein whose sequence is similar to that of truncated IsK can induce K+ channel activity when expressed in Xenopus oocytes, the inability of a truncated IsK to form functional K+ channels in planar lipid membranes supports increasing evidence that the protein alone cannot form a K+ channel. PMID- 8204632 TI - Role of the alpha C domains of fibrin in clot formation. AB - The role of the carboxyl-terminal portion of the alpha chains of fibrin (alpha C domains) in clot formation was investigated by transmission and scanning electron microscopy and turbidity studies of clots made from preparations of molecules missing one or both of these domains. Highly purified and entirely clottable preparations of bovine fragment X monomer, one containing primarily molecules missing a single alpha C domain (fragment X1) and the other consisting of molecules missing both alpha C domains (fragment X2), were used for these experiments. These preparations were characterized by various methods, including the complete determination of the amino- and carboxyl-termini of all peptides and fragments. These preparations formed clots on dilution to neutral pH. In all cases, clots observed by either scanning or transmission electron microscopy were made up of a branched network of fibers, similar to those formed by thrombin treatment of intact fibrinogen, suggesting that the alpha C domains are not necessary for protofibril and fiber formation or branching. However, both the fiber and clot structure varied with the different fractions, indicating that the alpha C domains do participate in polymerization. The rate of assembly, as indicated by the lag period and maximum rate of turbidity increase, as well as the final turbidity, was decreased with removal of the alpha C domains, suggesting that they accelerate polymerization. preparations of isolated alpha C fragment added to fibrin monomer have striking effects on the turbidity curves, showing a decrease in the rate of polymerization in a dose-dependent manner but not complete inhibition. Electron microscopy of fibrin monomer desA molecules at neutral pH showed that most of the alpha C domains, like those in fibrinogen, remain associated with the central region. Thus, it appears that normally with thrombin cleavage of fibrinogen the effects of the interactions of alpha C domains observed here will be most significant for lateral aggregation. PMID- 8204633 TI - Effects of autophosphorylation on casein kinase II activity: evidence from mutations in the beta subunit. AB - Casein kinase II is a heterotetramer composed of two catalytic (alpha) and two regulatory (beta) subunits. To examine the effects of autophosphorylation of the beta subunit on enzyme activity, two mutants of the beta subunit from Drosophila were constructed in which either Ser4 or Ser2-4 was changed to alanine residues by oligonucleotide-directed mutagenesis and the proteins were expressed in Escherichia coli. The wild-type alpha and individual beta subunits present in inclusion bodies were renatured, and the biochemical properties of the reconstituted holoenzymes were examined. Analysis of autophosphorylation revealed that phosphate incorporation was about 0.8 mol/mol of beta subunit for the wild type and Ala4 mutant; Ser2 and Ser3 were the major sites of autophosphorylation with some phosphate in Ser4 as shown by Edman degradation. No autophosphorylation was observed with the Ala2-4 mutant. Substitution of alanine for serine residues at positions 4 or 2-4 of the beta subunits did not influence the reassociation of the alpha and beta subunits to form holoenzyme, or the function of the beta subunit in stimulating catalytic activity or in responding to basic compounds. To measure the effects of autophosphorylation on casein kinase II activity, the wild type and mutant holoenzymes were preincubated in the presence and absence of ATP, and the rate of phosphorylation was measured with various substrates. In the absence of autophosphorylation, the wild-type, Ala4, and Ala2-4 forms of the holoenzyme displayed similar rates of phosphorylation of glycogen synthase. After preincubation with ATP, the rate of phosphorylation of glycogen synthase by the wild-type and Ala4 enzymes was inhibited by 30%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204635 TI - Checklist for the evaluation of research articles. PMID- 8204634 TI - Direct enthalpy measurements of factor X and prothrombin association with small and large unilamellar vesicles. AB - Isothermal titration calorimetry was used to determine the enthalpy for the calcium-dependent protein conformation change and subsequent interaction of blood clotting factor X and prothrombin with phospholipid vesicles. The effect of vesicle size was also determined. The protein conformation change was accompanied by -12 +/- 1 and -7 to -15 kcal/mol for factor X and prothrombin, respectively. The range of values for prothrombin arose from use of different protein preparations and may be due to non-ideal behavior of this protein when calcium was added. The apparent enthalpy of association (delta H(assoc)) of both factor X and prothrombin with phosphatidylserine (PS)/phosphatidylcholine (PC) large unilamellar vesicles (LUVs, 120 nm diameter) was shown to be near 0 kcal/mol. In comparison, delta H(assoc) for interaction with PS/PC small unilamellar vesicles (SUVs, 40 nm diameter) was -9 +/- 3 and -7 +/- 2 kcal/mol for factor X and prothrombin, respectively. This difference appeared complementary to delta H(assoc) for calcium binding to these vesicles. That is, the interaction of calcium was athermic with SUVs and exothermic with LUVs. While such properties might suggest a considerable difference in the manner of calcium binding to LUVs versus SUVs, little difference in the quantity of calcium bound to SUVs and LUVs was detected by equilibrium dialysis. In any event, the results indicate that protein binding to LUVs was primarily entropy driven whereas binding to SUVs was primarily enthalpy driven. The exothermic process for calcium-dependent factor X or prothrombin binding to SUVs may result from protein-induced changes in the phospholipid packing/calcium interaction, possibly related to changes in how calcium is bound to the phospholipid. PMID- 8204636 TI - Bibliography of recent journal articles (July to December 1992). PMID- 8204637 TI - The role of vitamin D in chorioallantoic membrane calcium transport. AB - 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) is essential for the transport of eggshell calcium to the embryo across the chorioallantoic membrane (CAM). CAM contains the vitamin D receptor that increases following 1,25-(OH)2D3 injection into embryos at day 10 of incubation. Further, a single injection of 100 ng of 1,25-(OH)2D3 into vitamin D-deficient quail eggs at day 10 of incubation resulted in a significant increase in both body and yolk calcium. This is accompanied by an increase in carbonic anhydrase from low levels in deficiency to normal levels. Acetazolamide (AZ), a specific carbonic anhydrase inhibitor injected into the quail embryos, caused hypocalcemia and hyperphosphatemia. This is similar to the hypocalcemia and hyperphosphatemia found in vitamin D-deficient embryos. These results suggest that one mechanism of action of vitamin D in the mobilization of eggshell calcium is the activation of carbonic anhydrase that acidifies the calcium carbonate shell. PMID- 8204638 TI - A biochemical-morphological study on microvillus plasma membrane development. AB - The microvillus plasma membrane of the human placental syncytiotrophoblast at term has been extensively studied, while little is known about the characteristics of its development. The aim of the present work was to compare functional and structural properties of this membrane at early and term gestational age. Ten normal term placentas (40 weeks) and ten placentas at 10 weeks of gestational age were studied. The Na+/K+-ATPase activity is significantly decreased in the syncytiotrophoblast plasma membrane obtained from term placentas as compared to the early ones, with significant variation of maximum velocity (Vmax). The microviscosity, evaluated by the P parameter of DPH and Sn parameters of 5- and 16-NS, is increased in the term placentas compared to the early placentas. This alteration is accompanied by an increased cholesterol to phospholipids ratio in term placentas, while there is a decreased unsaturated to saturated fatty acid ratio. As follows from morphological studies, an increased mean diameter in the E face was observed in the term placenta with respect to the early placenta. The distribution factor DF, which indicates the particle aggregation state, decreased in the E face in the term placenta as compared to the early one. The present biochemical morphological study shows that a deep modification of the membrane is at the basis of the syncytiotrophoblast plasma membrane development. PMID- 8204639 TI - Intracellular pH, cytosolic calcium concentration and electrical activity in RINm5F insulinoma cells. AB - The addition of L-lactate or acetate to RINm5F cells caused a transient intracellular acidification, an increase in [Ca2+]i and induced electrical activity. The subsequent withdrawal of lactate or acetate resulted in an intracellular alkalinization with no apparent changes in [Ca2+]i nor electrical activity. Intracellular alkalinization and acidification by application by application and withdrawal of NH4Cl were both accompanied by transient increases in [Ca2+]i in the absence of electrical activity. The induction of electrical activity by lactate was associated with the appearance of inward whole cell currents. Changes in intracellular pH may affect [Ca2+]i though not necessarily by altering plasma membrane potential. The inward currents associated with lactate application may represent an organic anion conductance contributing towards the stimulation of electrical activity by organic acids. PMID- 8204640 TI - Electrodiffusion of ethidium cation into Micrococcus luteus cells. AB - Ethidium bromide fluorescence increased in the presence of Micrococcus luteus cells; this was shown to be due to the interaction of the ethidium cation (Eth) with intracellular nucleic acids. Eth permeation across the cytoplasmic membrane was the rate-limiting step and obeyed first-order kinetics. Both the rate of influx and the amount of Eth in cells depended on respiration and on ATPase activity under aerobic and anaerobic conditions, respectively. The initial rate of uptake positively correlated with the membrane potential and was a linear function of Eth concentration in the range from 2 microM to 1 mM. The data indicate electrodiffusion of Eth into M. luteus. PMID- 8204641 TI - Affinity identification of organic anion transporters in brush-border membrane vesicles from rat kidney. AB - The inhibitory properties of bromoacetyl-p-aminohippuric acid as the affinity probe of the organic anion transport system were studied. Bromoacetylated p aminohippurate was shown to be able to inhibit irreversibly the p-aminohippurate (PAH) uptake in brush-border membrane vesicles. The inhibition depends on both the time of treatment and the affinity probe concentration. The treatment of brush-border membrane with 1 mM bromoacetyl-p-aminohippurate for 1.5 h results in 100% irreversible inhibition of PAH transport but no changes were observed in the activity of alkaline phosphatase, gamma-glutamyltranspeptidase or maltase. The affinity labelling of the organic anion transporters was performed with bromoacetyl-p-amino[3H]hippuric acid. It was shown, by means of SDS polyacrylamide gel electrophoresis, that the probe bound covalently to the brush border membrane proteins with molecular masses of 28 kDa, 63 kDa, 98 kDa, and > 150 kDa. The data obtained with SITS and probenecid as the organic anion transport inhibitors indicate that brush-border membrane proteins of 28 kDa, 63 kDa, 98 kDa may correspond to the organic anion transport system. PMID- 8204642 TI - Different sensitivities of native and oxidized forms of Na+/K(+)-ATPase to intracellular proteinases. AB - Inactivation of Na+/K(+)-ATPase by partially reduced oxygen metabolites has been implicated in ischemia-reperfusion injury to heart and other organs. Because oxidation of many proteins makes them more susceptible to degradation by intracellular proteinases, we studied the effects of several such proteinases on native and H2O2-oxidized preparations of Na+/K(+)-ATPase from canine kidney (containing alpha 1 isoform of the catalytic subunit) and rat axolemma (containing alpha 2 and alpha 3 isoforms). Lysosomal cathepsin D degraded the native and the oxidized preparations at acid pH, but it was significantly more effective against the oxidized forms. m-Calpain had little or no effect on the native Na+/K(+)-ATPase preparations, but it digested the oxidized alpha-subunits of the axolemma and the kidney enzymes. mu-Calpain's effects were similar to those of m-calpain. Multi-catalytic proteinase which is known to degrade a large number of oxidized proteins, did not affect the native or the oxidized forms of Na+/K(+)-ATPase. The findings suggest that (a) during oxidative stress there may be accelerated degradation of the oxidatively damaged Na+/K(+)-ATPase, either through internalization and transport to lysosomes, or by the action of calpains at the membrane; and (b) those isoforms of the enzyme that are more sensitive to oxidants are more susceptible to degradation by the above processes. PMID- 8204643 TI - Activity of phospholipase A2 on a fluorescent substrate incorporated into non hydrolyzable phospholipid liposomes. AB - The activity of phospholipase A2 (PLA2) on phospholipid liposomes depends on the physicochemical properties of the aggregated substrate, which are subject to continuous modification by the products released during hydrolysis. We propose here an experimental design that, by means of the incorporation of a fluorescent substrate at very low molar ratio (< or = 1:500) into a nonhydrolizable liposomal matrix of 1,2-dihexadecyl-sn-glycero-3-phosphocholine (DHPC), allows the study of hydrolysis by porcine pancreatic phospholipase A2, in virtual absence of physical perturbations of the lamellar phase, by the released products. We have been able to measure immediate hydrolysis of the fluorescent substrate 1,2-di-[omega(1' pyreno)-decanoyl]-sn- glycero-3-phosphocholine when the sonicated liposomal matrix is in the gel phase. In the liquid crystalline state, in contrast, hydrolysis is very poor even after 80 min of adding the enzyme. Both in the gel and liquid-crystalline phases, incorporation of unlabeled PLA2 products activates the hydrolysis rate to comparable levels. It appears that the conformation adopted by the substrate immersed in the gel or liquid crystalline matrix is especially important in determining its susceptibility to hydrolysis in the absence of products. PMID- 8204644 TI - Electron microscopic investigations on free-standing mixed lipid Langmuir Blodgett-Kuhn monolayers: phase separation and aging process. AB - Lipid monolayers were prepared by the Langmuir-Blodgett-Kuhn technique (LBK) as free-standing films spanning a diameter of up to 1 micron. These films were investigated by electron spectroscopic imaging (ESI) and electron energy loss spectroscopy (EELS). The free-standing monolayer is shown to be in a transient state in which an aging process is proceeding: after storage for two weeks in air at room temperature the films tear off the edges of the perforated supporting film. Ca2+ ions induced lateral phase separation in these films prepared from a 50:50 mixture of lecithin/glycerol could be visualized by means of ESI, i.e., by comparing micrographs below and above the Ca absorption edge in the EEL spectrum. The domain sizes of the demixed phases were determined to vary between 30 and 60 nm. In addition it was shown that the counter ion of the negatively charged glycerol in these films is Ca2+ and not Na+. PMID- 8204645 TI - cAMP-dependent protein kinase is not involved in catabolite inactivation of the transport of sugars in Saccharomyces cerevisiae. AB - It has been reported that catabolite inactivation of sugar transport systems in Saccharomyces cerevisiae requires cAMP-dependent protein kinase activity (cAPK) and that the levels of these transport systems are decreased in the absence of a functional cAPK regulatory subunit. We have re-examined these possibilities and have found that catabolite inactivation does not require cAPK activity and that normal levels of the transports occur independently from the presence of the regulatory subunit. With the available information, it is difficult to ascertain the reasons for the discrepancy between our results and the ones previously reported. The inadequacy of the method used to measure the sugar transport activities might contribute to this discrepancy. PMID- 8204646 TI - Phospholipid transverse asymmetry in trout spermatozoa plasma membrane. AB - The phospholipid transmembrane distribution and movement in the plasma membrane of rainbow trout spermatozoa was determined with spin-labelled phospholipid analogues. After initial incorporation in the outer membrane leaflet, only the aminophospholipids, phosphatidylserine (PS) and phosphatidylethanolamine (PE) redistributed towards the inner leaflet. At equilibrium, more than 90% PS and approximately 80-85% PE were located in the cytoplasmic leaflet. The inward motion was significantly faster for PS (t1/2 approximately 5 min) than for PE (t1/2 approximately 60 min). Both the velocity and the extent of this redistribution were dependent on the cellular ATP level, arguing for the involvement of the aminophospholipid translocase. Comparison of the electron paramagnetic resonance spectra recorded from analogues located in either one of the leaflet showed an important difference of microviscosity between the cytoplasmic and the extracellular bilayer leaflets. Assuming that the analogue distribution reflects the asymmetry of the endogenous phospholipids, the higher probe mobility in the inner leaflet could be correlated to a higher degree of unsaturation of the fatty acids present in this hemi-leaflet. PMID- 8204647 TI - Dynamics of merocyanine 540 in model biomembranes: photoisomerization studies in small unilamellar vesicles. AB - The fluorescence lifetime, tau f, of merocyanine 540 (MC540) in small unilamellar vesicles was measured as a function of temperature and cholesterol content by using phase modulation fluorometry. These vesicles were formed by probe sonication of aqueous suspensions of egg phosphatidylcholine (PC) and cholesterol. The fluorescence lifetime of MC540 in these vesicles decreased with increasing temperature, but was independent of cholesterol. The decrease in tau f with temperature is attributed to trans-cis photoisomerization. At low temperatures, the inverse of tau f, or the fluorescence rate constant, kf, approaches a constant value of 0.45 +/- 0.02 ns-1, which corresponds to the value of the radiative rate constant, kr, of the dye. The photoisomerization rate constant, kiso, was obtained by subtracting kr from kf. The temperature dependence of kiso is well described by an Arrhenius equation, with an activation energy of 31.5 +/- 0.9 kJ mol-1. This Arrhenius behavior is rationalized in terms of the Smoluchowski limit for the Kramers theory for activated barrier crossing. The electronic spectra and kiso for MC540 in these vesicles are consistent with the dye being located in the polar headgroup region of the lipid bilayer. PMID- 8204648 TI - Liposome-induced activation of the classical complement pathway does not require immunoglobulin. AB - We have investigated the contribution of immunoglobulin to the liposome-induced activation of complement in human serum. Liposomes containing the negatively charged phospholipids cardiolipin, phosphatidylglycerol or phosphatidylinositol, in addition to phosphatidylcholine and cholesterol, were used to activate complement in a whole serum system. The contribution of immunoglobulin was studied by comparing normal human serum (NHS) to serum depleted of IgG and IgM (DDS). Using hemolytic assays of complement function, greater concentrations of phospholipids were required to activate complement in the absence of immunoglobulins. Activation of the classical pathway was confirmed using a C1q ELISA which showed that activation was dependent on the presence of C1q and confirmed that greater concentrations of phospholipids were required to activate complement in the absence of immunoglobulins. Complement activation was also assessed using crossed immunoelectrophoresis of C3 activation fragments. Using immunoblot analysis, iC3b was detected on the surface of liposomes exposed to NHS or DDS. These studies demonstrate that when liposomes, containing anionic phospholipids at an equivalent charge to cardiolipin 20 mol%, are exposed to immunoglobulin depleted serum they become opsonized by complement proteins. PMID- 8204649 TI - Reconstitution of hepatitis B surface antigen proteins into phospholipid vesicles. AB - Hepatitis B surface antigen (HBsAg), devoid of 75% of its total lipids has been reconstituted with several phospholipids by the detergent dialysis method, using the non-ionic detergent beta-D-octyl glucoside. Upon reconstitution with both neutral and acidic phospholipids, HBsAg particles had the same morphology and, as indicated by trypsin hydrolysis, the topology of the surface proteins was maintained. However, only negatively charged phospholipids were able to completely revert the conformational changes which had been induced by removal of the lipids. The helical content, as indicated by CD techniques, and the antigenic activity, as measured by binding to polyclonal antibodies, of HBsAg reconstituted with acidic phospholipids were practically identical to those of the native antigen. Cholesterol had no effect on the antigenic activity recovered by reconstitution with any of the phospholipids. PMID- 8204650 TI - Localization of the hinge region of the Ca(2+)-ATPase of sarcoplasmic reticulum using resonance energy transfer. AB - The Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum can be labelled at Cys-670 and Cys-674 with 5-[[2-[(iodoacetyl) amino]ethyl]amino]naphthalene-1 sulphonic acid (IAEDANS). Resonance energy transfer has been used to measure the distance between Cys-670/Cys-674 and Glu-439 labelled with 5 (bromomethyl)fluorescein as 40 A. The height of Cys-670/Cys-674 above the phospholipid/water interface has been measured by resonance energy transfer between IAEDANS-labelled ATPase and fluorescein-labelled phosphatidylethanolamine as 54 A. This locates the hinge region of the ATPase close to the mouth of the pore observed in the cytoplasmic region of the ATPase in electron micrographs. No significant changes in these distances can be detected by resonance energy transfer on binding Ca2+ or vanadate. The height of the IAEDANS label above the phospholipid/water interface is the same for bilayers of dimyristoleoylphosphatidylcholine and dioleoylphosphatidylcholine. Conformation changes on the Ca(2+)-ATPase appear to be localised to small regions of the ATPase. PMID- 8204651 TI - Permeability and stability in buffer and in human serum of fluorinated phospholipid-based liposomes. AB - The stability (with respect to encapsulated carboxyfluorescein release) of fluorinated liposomes and their membrane permeability have been investigated in buffer and in human serum as compared to conventional hydrogenated analogues. These fluorinated liposomes are made from highly fluorinated phosphatidylcholines and contain a fluorinated core within their membrane. In buffer and in their fluid state, the fluorinated liposomes retain much more efficiently their entrapped content and display lower membrane permeability coefficients than any of their hydrogenated counterparts. This indicates that the fluorinated core acts as a very efficient barrier to permeation. In terms of molecular structure/permeability relationships, the thicker the fluorinated lipophobic core, the more efficient the barrier to permeation. In their gel state, the fluorinated core has, however, almost no effect on permeation. Interestingly, some of the 'fluid' fluorinated liposomes were even less permeable than 'gel' or 'gel-like' ones, including egg phosphatidylcholines/cholesterol liposomes. Human serum destabilizes the 'fluid' fluorinated liposomes but to a lesser extent than the 'fluid' hydrogenated ones, indicating that the fluorinated lipophobic core inside the liposomal membrane protects the vesicles, possibly by reducing their interactions with serum components. 'Gel' or 'gel-like' fluorinated liposomes are significantly more stable in serum than in buffer. They are also more stable than conventional 'gel' or 'gel-like' liposomes. PMID- 8204652 TI - Trehalose lowers membrane phase transitions in dry yeast cells. AB - Recent work has clearly demonstrated a direct correlation between the amount of trehalose present in the yeast Saccharomyces cerevisiae and its ability to tolerate dehydration, but has failed to elucidate the specific role played by trehalose. By using Fourier transform infrared spectroscopy we measured the transition temperature of phospholipids in both intact S. cerevisiae and isolated plasma membranes dried in the presence and absence of trehalose. Our results show that trehalose lowers the temperature of the dry gel to liquid crystal phase transition in yeast from around 60 degrees C to about 40 degrees C, thus allowing yeast rehydrated above 40 degrees C to avoid the damaging effects of passing through a phase transition. These results explain both the need for trehalose and the observation that yeast must be rehydrated with warm water if they are to remain viable. Only when trehalose is present is the dry transition within a physiologically tolerable range and only when the cells are rehydrated above 40 degrees C will they avoid passing through a phase transition. PMID- 8204653 TI - Significant stabilization of the phosphatidylcholine bilayer structure by incorporation of small amounts of cardiolipin. AB - The effects of the negatively charged phospholipid cardiolipin on the structural properties of egg-yolk phosphatidylcholine (EyPC) liposomal membranes were studied by monitoring the water permeability of the liposomes caused by osmotic shrinkage in hypertonic glucose solution. Incorporation of small amounts of bovine heart cardiolipin (BhCL) into the EyPC membranes caused a significant decrease in their water permeability associated with stabilization of the membrane structure. Much evidence obtained by attenuated total reflection IR spectroscopy suggested that incorporation of BhCL into the EyPC membranes causes a cooperative conformational change in the EyPC polar head groups, but does not alter the fluidity of the bilayer structure in the fluid liquid crystalline state. Incorporation of small amounts of BhCL stabilized the intermolecular hydrogen-bonded network including water molecules of the hydration layers at the bilayer surface that are important for the stable bilayer configuration of the EyPC molecules. The antisymmetric PO2- frequencies of the EyPC membrane with incorporated BhCL suggested that the BhCL content of 50 mol% induced a change in the phase behaviors of mixed BhCL/EyPC membranes. PMID- 8204654 TI - Voltage- and Ca(2+)-dependence of the K+ channel in the vacuolar membrane of Chenopodium rubrum L. suspension cells. AB - Voltage- and Ca(2+)-dependence of the slow-activating SV-K+ channel in the vacuolar membrane of Chenopodium rubrum suspension cells has been analyzed using the patch clamp technique in the vacuole-attached, outside-out and whole-vacuolar configuration. Patch-pipette perfusion was applied to measure Ca2+ dependence of single channels in the attached-configuration. Using the PCLAMP-software (Axon Instruments), an algorithm was developed to extract reliable individual channel data from multi-channel activity records, including open probability, mean open and closed times, as well as time constants for open and closed distributions. The channel conductance of the major open state was about 83 pS (seal resistance > 8 G omega) at 30 mV (transmembrane voltage Vm, vacuole negative), and symmetrical 100 mM KCl. the channel exhibited a strong voltage- and a weak Ca(2+) activation: increasing Vm from 40 to 100 mV is equivalent to a Ca2+ concentration change from 10(-7) to 10(-4) M. Mean open probabilities at Vm = 30 mV were 0.03 with 1 microM and 0.09 with 100 microM Ca2+. Mean open times were approx. 7 ms, and almost independent of both, voltage and Ca2+. Mean closed times, however, varied in a strongly voltage- and Ca(2+)-dependent manner, e.g., at Vm = 30 mV dropped from 205 to 67 ms, if Ca2+ was raised from 10(-6) to 10(-4) M. Open and closed distributions of events within bursts could be fitted by the sum of two exponentials with time constants between 0.3 and 11 ms. PMID- 8204655 TI - Phospholipid asymmetry in plasma membrane vesicles derived from BHK cells. AB - The transbilayer distribution of phospholipids in plasma membrane vesicles derived from BHK cells by treatment with iodoacetamide or fluoride and merocyanine 540 has been examined by exposing the vesicles to bee venom phospholipase A2 (PLA2) or to Bacillus cereus sphingomyelinase. The results show that almost all of the phosphatidylserine (PS) is on the inner lipid leaflet and most of the sphingomyelin is on the outer lipid leaflet. In contrast, about 50% of the phosphatidylcholine (PC) and 30-40% of the phosphatidylethanolamine (PE) is rapidly degraded by PLA2 and thus appears to be present on the surface of the vesicles. The pools of PC and PE which are accessible only slowly to PLA2 are degraded with halftimes of about 5 h and 2 h, respectively, and it is suggested that this rate reflects the rate of transbilayer migration of these lipids. We conclude that the profound energy depletion caused by treatment with iodoacetamide or fluoride does not alter the asymmetric distribution of PS across the plasma membrane but does have a marked effect on the transbilayer distribution of PE. Residual cells after treatment with fluoride and MC540 were also exposed to PLA2. The results were broadly in agreement with those obtained with vesicles, suggesting that the vesicles were representative of the BHK cell plasma membrane in terms of phospholipid asymmetry. Fluoride or MC540 added separately caused little vesicle release but did lead to significant loss of phospholipid asymmetry. When centrifuged on a sucrose density gradient, vesicles were separated into two major fractions accounting for about two thirds and about 20%, respectively, of total phospholipid but no significant differences were seen in the transbilayer phospholipid asymmetry of the two fractions. PMID- 8204656 TI - Expression of Na+-independent isoleucine transport activity from rat brain in Xenopus laevis oocytes. AB - Poly(A)+ RNA from C6-BU-1 rat glioma cells and rat astroglial cells induced isoleucine transport activity when injected into Xenopus laevis oocytes. The Na+ independent component of isoleucine transport was inhibited by leucine, phenylalanine and 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH) but neither by methylaminoisobutyric acid (MeAIB) nor lysine. A Km value of approx. 100 microM was determined for the Na+-independent transport of isoleucine. These data are in accordance with expression of a system L like transporter. By injection of size fractionated poly(A)+ RNA a length of approx. 1.9 kb was determined for the pertinent mRNA. PMID- 8204657 TI - Latency of cathepsin B secreted by human colon carcinoma cells is not linked to secretion of cystatin C and is relieved by neutrophil elastase. AB - The lysosomal cysteine proteinase cathepsin B is shown to be secreted by ten human colon carcinoma cell lines and to accumulate in culture media as a latent enzyme. The cell lines also secrete a physiological inhibitor of cathepsin B, cystatin C. A significant correlation was found between secretion of the latent enzyme and the inhibitor (r = 0.755, P < 0.01). The aim of the present study was to modulate the respective secretion of the two antagonists to test whether or not latency of cathepsin B was due to the concomitant secretion of the inhibitor. SW480 colon carcinoma cells were treated with the acidotropic agent ammonium chloride, phorbol 12-myristate 13-acetate, and the inflammatory cytokines TGF beta, TNF-alpha, and IL-1 beta. Ammonium chloride significantly increased latent cathepsin B levels without affecting the constitutive secretion of cystatin C. Phorbol 12-myristate 13-acetate induced a 4- to 5-fold increase in secreted latent cathepsin B, but did not alter significantly the accumulation of cystatin C in media. The cytokines, TGF-beta, TNF-alpha, and IL-1 beta, had no major effect on the expression of these two antagonists. Latent cathepsin B released from human carcinoma cells could be efficiently activated by neutrophil elastase at neutral pH. It is concluded that latent cathepsin B is a true proenzyme rather than an enzyme-inhibitor complex. In addition, our data from neutrophil elastase activation experiments indicate that a proteolytic system for activation of the tumor cell-secreted latent enzyme may exist in vivo. PMID- 8204658 TI - Studies of in vitro gamma-interferon production in coeliac disease as a response to gliadin peptides. AB - The effects of certain fractions of a peptic-tryptic-pancreatinic (PTP) digest of wheat gliadin and of synthetic peptides on the production of gamma interferon (gamma-IFN) in cultures of whole blood from adult patients with coeliac disease (CD) have been studied using a sandwich enzyme immunoassay. The most active peptides were fraction 9, its two principal sub-fractions (sub-fractions 1 and 2) and a synthetic peptide of sequence RPQQPYPQPQPQ (peptide V) corresponding to the principal peptide obtained from reversed-phase HPLC of fraction 9. Results with blood from the control group of subjects also indicated some response to these antigens, in most cases at similar levels to those observed with the coeliacs. Fraction 1 of the PTP digest and the other nine synthetic peptides tested were inactive with both coeliacs and controls. These results are in agreement with the results of in vivo and in vitro toxicity tests. They provide evidence of a link between toxicity and cell-mediated immune response in CD, and suggest that peptide V represents one of the active parts of the gliadin molecule. PMID- 8204659 TI - The displacement of calcium from osteocalcin at submicromolar concentrations of free lead. AB - Lead, an environmental toxin, is known to impair some of the functional properties of osteocalcin, a small protein (MW, 5700) active in bone mineralization and resorption. To investigate a possible mechanism of lead toxicity at the molecular level, we have studied the interaction of lead with osteocalcin using 43Ca and 1H NMR. The measured 43Ca NMR linewidth as well as longitudinal relaxation rate (1/T1) of 43CaCl2 progressively increased with increasing amounts of added osteocalcin. A titration measuring 43Ca linewidth as a function of [Ca2+]/[Osteocalcin] ratio could be fitted to a single metal binding site with a dissociation constant of 7 microM. The 43Ca 1/T1 of Ca osteocalcin decreased in the presence of Pb2+ due to competitive displacement of Ca2+ by Pb2+. The magnitude of decrease in the effect of osteocalcin on 43Ca 1/T1 in the presence of Pb2+ was consistent with the existence of only one tight divalent cation binding site. An analysis of the NMR T1 data in osteocalcin solutions containing both Pb2+ and Ca2+ yielded a Pb-osteocalcin dissociation constant of about 2 nM. The 1H NMR spectra showed Pb-induced changes in the same aliphatic and aromatic resonances of osteocalcin that are also affected by Ca(2+) binding, supporting interaction of Pb2+ at the Ca2+ site. However, the existence of significant differences between the Pb-osteocalcin and Ca-osteocalcin NMR spectra indicates some differences in the structures of the two complexes. Since Pb2+ inhibits the binding of osteocalcin to hydroxyapatite, the high affinity of Pb2+ for osteocalcin would indicate significant inactivation of osteocalcin even at submicromolar free lead levels. Pb(2+)-induced inactivation of osteocalcin could affect bone mineral dynamics and may be related to the observed inverse correlation between blood Pb(2+)-levels and stature and chest circumference observed in growing children. PMID- 8204660 TI - Free sphingoid bases in tissues from patients with type C Niemann-Pick disease and other lysosomal storage disorders. AB - The 20-fold increase of free sphingoid bases found in liver from a murine model of Niemann-Pick type C (NPC) combined to the NPC-like phenotype induced by addition of sphinganine to normal fibroblast cultures prompted us to investigate the potential involvement of these compounds in the human disease. The contents of sphingosine and sphinganine were measured in liver, spleen, brain and skin fibroblast cultures by a sensitive HPLC method. In liver and spleen from NPC patients, a 6- to 24-fold elevation of sphingosine and sphinganine already prominent at the fetal stage of the disease was observed, while no clear increase could be evidenced in brain tissue. A significant increase, not modulated by the intralysosomal content of free cholesterol, also occurred in skin fibroblast cultures. To investigate the specificity of these findings, other lysosomal storage disorders were studied. A striking accumulation was found in liver and spleen (24- to 36-fold) from patients with Niemann-Pick disease type A and B (sphingomyelinase-deficient forms), and in cerebral cortex of type A Niemann-Pick disease. A significant storage also occurred in Sandhoff disease, while several other sphingolipidoses showed a moderate elevation. In all cases but Sandhoff disease brain, the sphingosine/sphinganine ratio remained unchanged, suggesting that the accumulated free sphingoid bases derived from sphingolipid catabolism. Formation of complexes between sphingosine and the lipid material accumulated in lysosomes might be a general mechanism in lysosomal lipidoses. In NPC, however, an increase of free sphingoid bases disproportionate to the degree of lysosomal storage and a specific involvement of cultured fibroblasts suggested a more complex or combined mechanism. PMID- 8204661 TI - Inhibition of glycolytic enzymes by endogenous aldehydes: a possible relation to diabetic neuropathies. AB - Endogenous saturated and unsaturated aldehydes were found in significant elevations in serum of diabetic humans and rats. These compounds, originating from the lipid peroxidation processes, are shown here to be potent inhibitors of the glycolytic enzymes, phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. The inhibition process is non-competitive and progressive. The aldehyde mixture, when supplemented to the standard rat diet at 1/100 ratio, caused nerve damage that is reminiscent of diabetic polyneuropathies. PMID- 8204662 TI - Cell-substrate adhesion and metastatic potential of cultured mesothelioma cells induced by asbestos. AB - Cell-substrate adhesion was quantified for two cultured mesothelioma cell lines (epitheliomatous and sarcomatous) on glass, fibronectin and laminin substrates. Interference reflection microscopy (IRM) was used to image the adhesion patterns of cells and a grey level analysis was employed to quantify adhesion. Sarcomatous cells demonstrated marked adhesion to glass and fibronectin-coated substrates but not to laminin-coated substrate, with the greatest adhesion occurring on the fibronectin-coated surface. This adhesion was accompanied by cytoplasmic spreading. By contrast, epitheliomatous cells showed little tendency to adhere to any of the substrates and only showed significant spreading when in contact with the laminin substrate (P < 0.01). A bioassay was used to determine the metastatic potential of each of the cell lines. Via the intravenous route, the sarcomatous cells killed the host rats in 24.7 +/- 1.5 (S.D.) days compared to 27.3 +/- 0.9 (S.D.) days for the epitheliomatous cells (P < 0.01). After subcutaneous inoculation of tumour cells, the sarcomatous cells killed the host rats in 54.7 +/- 0.7 (S.D.) days compared to 48.5 +/- 0.5 (S.D.) days for the epitheliomatous cells (P < 0.01). We conclude that the results of the metastasis bioassays were consistent with the predicted behavior of these cell lines based on their ability to adhere to substrates in the in vitro adhesion assays. PMID- 8204663 TI - Identification of the site of glycation of gamma-II-crystallin by (14C)-fructose. AB - Cataract formation in diabetes may be via non-enzymic glycosylation (glycation) of lens proteins due to increased concentrations of sugars present in the lenses of diabetic patients. The objective of this project was to identify the site(s) of glycation of bovine gamma-II-crystallin by [14C]fructose. gamma-II-crystallin was isolated from soluble lens nucleus proteins by gel chromatography, followed by ion-exchange chromatography and was then glycated by incubation with [14C]fructose. Radioactively labelled gamma-II-crystallin was cleaved with trypsin. Affinity chromatography of the tryptic peptides gave a single main peak containing the majority of the radioactivity. This indicated that fructose had reacted at a single site on the protein. Amino acid analysis of this peptide showed it to contain only lysine and a trace amount of glycine. By relating the results of the amino acid analysis to the amino acid sequence of gamma-II crystallin, it was concluded that the labelled peptide corresponded to the N terminal dipeptide. The site of glycation of bovine gamma-II-crystallin by fructose was thereby identified as the alpha-NH2 group of the N-terminal glycine. PMID- 8204664 TI - Structural organization and analysis of the human fumarylacetoacetate hydrolase gene in tyrosinemia type I. AB - Fumarylacetoacetate hydrolase (FAH) is a metabolic enzyme functioning at the last step of tyrosine catabolism. Deficiency in this enzyme activity is associated with tyrosinemia type I, characterized by hypertyrosinemia, liver dysfunction, renal tubular dysfunction, liver cirrhosis, and hepatic tumors. We isolated from a human gene library a chromosomal gene related to FAH. The human FAH gene is 30 kilobases long and is split into 14 exons. All of the splice donor and acceptor sites conform to the GT/AG rule. We also analyzed findings in a patient with tyrosinemia type I with respect to the mutation responsible for defects in the enzyme. A nucleotide change from T to G was found in the exon 2 of the gene and this change was accompanied by an amino acid substitution (Phe62Cys). Transfection and expression analysis of the cDNA in cultured BMT-10 cells with the nucleotide substitution demonstrated that the substitution was indeed responsible for the decreased activity of the enzyme in the patient. These results confirmed that the T to G mutation was one of the causes of tyrosinemia type I. Structure of the FAH gene and tests for expression of the mutant FAH will facilitate further understanding of various aspects of FAH. PMID- 8204665 TI - Regulation of intracellular cholesterol metabolism is defective in lymphoblasts from Niemann-Pick type C and type D patients. AB - Regulation of intracellular cholesterol metabolism has been studied in Epstein Barr virus-transformed lymphoblasts from patients with Niemann-Pick type C (NPC) and the Nova Scotia type D (NPD) disease. Addition of LDL to normal lymphoblasts cultured in lipoprotein-deficient medium increased cholesterol esterification 10 fold (to a maximum of 1.0 nmol/h/mg protein at 15 h), while little stimulation was seen in NPC cells. The response by NPD lymphoblasts was intermediate, reaching approximately half of normal values by 14-24 h. Lymphoblasts from both NPC and NPD obligate heterozygotes exhibited 50% of normal LDL-stimulated cholesterol esterification at 6 h, when activity was < 10% of normal values in patient cells. Fluorescence staining with filipin indicated excessive intracellular accumulation of LDL-derived cholesterol in both NPC and NPD lymphoblasts. Downregulation of LDL receptor mRNA levels by LDL, measured by S1 nuclease protection assay, was also impaired in NP lymphoblasts and fibroblasts (NPC > NPD), although a similar rate of receptor protein down-regulation by LDL (t1/2 = 10-15 h) was observed in normal and NP lymphoblasts. In contrast, LDL down-regulation of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA did not appear to be affected in NP cells: LDL produced a 3-fold (lymphoblasts) or > 10-fold (fibroblasts) decrease by 12 h in both normal and affected cells. Thus, NPC and NPD lymphoblasts exhibit distinct defects in cholesterol esterification and storage, similar to those observed in mutant fibroblasts. Other regulatory responses are also impaired in NPC lymphoblasts but appear to be less affected in NPD cells. Lymphoblasts should provide a valuable immortalized cell line model for study of defective regulation of cholesterol esterification and transport in Niemann-Pick type II disease, and may also be suitable for diagnosis and carrier detection. PMID- 8204666 TI - Defective tetrahydrobiopterin and catecholamine biosynthesis in the depigmentation disorder vitiligo. AB - Patients with the depigmentation disorder vitiligo lack the capacity to synthesize the melanins from L-tyrosine via the essential activity of tyrosinase. The aim of this study has been to examine both the supply of the substrate (L tyrosine) and the regulation of tyrosinase in the epidermis of subjects with vitiligo. Patients with this depigmentation disorder have a 3- to 5-fold increase in GTP-cyclohydrolase I activity leading to an excessive de novo synthesis of (6R)5,6,7,8 tetrahydrobiopterin (6-BH4). Continuous production of 6-BH-4 leads to: (1) an accumulation of the non-enzymatic byproduct 7-tetrahydropterin (7-BH4) in the epidermis, and (2) increased synthesis of the catecholamines in keratinocytes, leading to an excess of norepinephrine in both the plasma and urine of these patients. In vitiligo, the time-dependent production of 7-BH4 is caused by decreased 4a-hydroxytetrahydrobiopterin dehydratase activity; the essential enzyme for recycling and maintaining normal levels of 6-BH-4. In the epidermis and in cultured melanocytes, 7-BH4 is a potent competitive inhibitor of phenylalanine hydroxylase (Ki = 10(-6) M) and its accumulation in the epidermis of patients with vitiligo blocks the supply of L-tyrosine from L-phenylalanine. 4a-hydroxytetrahydrobiopterin dehydratase has a dual function as the activator/dimerization catalyst for the transcription factor hepatocyte nuclear factor I (HNF-I). HNF-I binds to a 16-base inverted palindrome which seems to be present on the promoters of both the tyrosinase and phenylethanolamine-N-methyl transferase (PNMT) genes. Therefore, defective 4a-hydroxytetrahydrobiopterin dehydratase in vitiligo influences not only the supply of L-tyrosine but also the transcription of the tyrosinase gene in melanocytes. Furthermore, a similar transcriptional regulation of the PNMT gene in keratinocytes offers a possible explanation for the accumulation of norepinephrine in these patients. PMID- 8204667 TI - Effects of transforming growth factor beta and interleukin-1 beta on [3H]thymidine incorporation by human articular chondrocytes in vitro. AB - This is a study of the regulation of human articular chondrocyte proliferation by transforming growth factor beta (TGF beta) and interleukin-1 beta (IL-1 beta) in vitro. Human articular chondrocytes were cultured at different cell densities on plastic and on a collagen substratum, in the presence and absence of serum. The effects of TGF beta and IL-1 beta on proliferation of chondrocytes, as determined by [3H]thymidine incorporation, under these conditions of culture were examined. TGF beta was found to have both stimulatory and inhibitory effects on chondrocytes in vitro. Interactions between TGF beta and growth factors present in serum influence the modulation of chondrocyte proliferation by TGF beta. IL-1 beta caused a significant reduction of the TGF beta-stimulated increase in chondrocyte proliferation. The complex inter-relationships between TGF beta and IL-1 beta on chondrocytes have implications for cartilage repair. PMID- 8204668 TI - Enhanced expression of group II phospholipase A2 in human hepatocellular carcinoma. AB - Enzyme activity, protein contents, and mRNA contents of group II phospholipase A2 (PLA2) in hepatocellular carcinoma (HCC) surgically obtained from 8 patients were compared with those in either its neighboring liver tissues or control liver tissues. The PLA2 specific activity towards the mixed micelles of 1-palmitoyl-2 oleoyl-phosphatidylglycerol and cholate was significantly greater in the tumor tissues (6.62 +/- 1.46 nmol/min/mg) than those in the surrounding liver tissues (1.33 +/- 0.22 nmol/min/mg) and controls (0.43 +/- 0.04 nmol/min/mg). The results of immunoblot analysis using a specific anti-human group II PLA2 antibody and of Northern blot analysis using a human group II PLA2 cDNA as a probe demonstrated that group II PLA2 was responsible for the increased enzyme activity. The contents of immunoreactive group II PLA2 in the tumor tissues (8.81 +/- 1.24 ng/mg) were significantly higher than those in the surrounding liver tissues (1.74 +/- 0.27 ng/mg); those in the control tissues were below the analytical range of the method used. The group II PLA2 mRNA was also significantly increased in the tumor tissues, compared with that in the surrounding liver tissues, whereas it was not detectable in the controls. This indicates that group II PLA2 in HCC is induced at the pretranslational level. PMID- 8204669 TI - Is sorbitol dehydrogenase gene expression affected by streptozotocin-diabetes in the rat? AB - The polyol pathway, which comprises the enzymes aldose reductase and sorbitol dehydrogenase, is recognised to play a major role in the pathogenesis of diabetic complications. Although there has been extensive research on aldose reductase, the role of sorbitol dehydrogenase has been overlooked. This study examined the response of sorbitol dehydrogenase gene expression to streptozotocin-diabetes (STZ-diabetes) in the rat and whether these changes were reversed by insulin. STZ diabetes increased testicular sorbitol dehydrogenase gene expression in a manner that was not reversible by insulin but had no effect on gene expression in kidney and brain. A secondary question was the relationship between sorbitol dehydrogenase and aldose reductase gene expression in STZ-diabetes. STZ-diabetes increased renal aldose reductase gene expression in a manner that was not reversible by insulin but had no effect on gene expression in the brain, testes and muscle. Thus, STZ-diabetes causes changes in sorbitol dehydrogenase gene expression which do not parallel those in aldose reductase, implying that expression of the two genes is not regulated via a common mechanism. Furthermore, changes in sorbitol dehydrogenase and aldose reductase gene expression cannot be fully explained on the basis of the osmoregulatory hypothesis, suggesting that regulation is mediated via mechanisms that are multifactorial and tissue specific. PMID- 8204670 TI - Purification and characterization of glutathione peroxidase from human blood platelets. Age-related changes in the enzyme. AB - Platelet glutathione peroxidase (GPx) is known to play a pivotal role in controlling the level of lipid hydroperoxides, especially those resulting from the 12-lipoxygenase activity. GPx was purified from the cell cytosol by more than 700-fold using an exchange chromatography, FPLP, gel filtration and covalent fixation. Isoelectric focusing revealed a peak activity at pH 5.1. The molecular mass of the enzyme was found between 90 and 100 kDa by gel filtration, and was approximating at 23 kDa by SDS-PAGE. A polyclonal antibody raised against commercial bovine erythrocyte GPx recognized the human platelet enzyme. It is concluded that human platelet GPx is likely a homotetramer of 92 kDa as described for most other sources. We have also found that the decreased platelet GPx activity observed in platelets from elderly people is associated with a lower content of the immunoreactive enzyme. PMID- 8204671 TI - Drugs of abuse and dysfunction of neuroendocrine and immune systems: the importance of animal research. PMID- 8204672 TI - Substance use and abuse: research studies. PMID- 8204673 TI - The effect of intimate exposure to alcohol abuse on the acquisition of knowledge about drinking. AB - This study explored how an alcohol education program might be structured to effectively educate college students about the consequences of alcohol use. The primary hypothesis tested stated that individuals would vary significantly in the amount of knowledge learned from a structured alcohol education workshop, based on the degree of familial or social exposure s/he has had to alcohol abuse. Social learning variables of locus of control, dogmatism, and expectancy for risk were tested for interaction with degree of exposure, to determine their influence on learning. A pretest-posttest control group was employed with a sample of 66 undergraduate college students. A four hour alcohol education program was administered to teach cognitive information and fact about alcohol, with a goal of facilitating responsible use/nonuse of alcohol. The Student Drinking Questionnaire measured acquisition of knowledge. The Adult Nowicki-Strickland Internal/External Scale measured locus of control, and Schultze's Short Dogmatism Scale measured dogmatism. The researcher developed an instrument for expectancy for risk. Multiple regression analyses yielded prediction equations for the variables under study. For the sample group, results demonstrated that a significant portion of the variance in the residualized posttest scores was accounted for by level of exposure and dogmatism. When the sample was blocked according to intimate or social exposure, dogmatism was the only construct entering the regression equation at a significant level for the intimate exposure group. None of the constructs were able to predict any of the residualized posttest scores for the social exposure group. It was concluded that: (1) Students in the sample learned differentially based on the degree of intimate exposure of alcohol; (2) Dogmatism is a moderating variable with acquisition of knowledge for those intimately exposed to alcohol abuse, but locus of control and expectancy for risk are not; and (3) Further research is needed to study the effects of differential learning goals set for different populations. PMID- 8204674 TI - Some problems with the anti-prohibitionist position on legalization of drugs. AB - The pro-legal position has mounted cogent arguments to support conclusions that the existing prohibition policy has failed and that legalization, while not a solution to the drug use problem, will effectively eliminate drug related crime. The premise of this article is that a legalization policy is wrong in that the basic assumptions underlying the anti-prohibitionist position are flawed. Prohibition has operated in a social vacuum. It has been an isolated effort substituting for an integrated and well coordinated approach which includes prevention, treatment as well as enforcement and supported by an educated public resolve against illicit drugs. PMID- 8204675 TI - Homeland, gender and Chinese drinking. AB - Taiwan and Hong Kong represent areas of rapid industrial development and the attention of traditional Chinese attitudes toward drinking. To measure the influence of the different homelands on alcohol consumption, a survey of 150 foreign Chinese students (94 males and 56 females) was conducted. In terms of homeland, 95 participants (63.3%) were from mainland China, 29 (19.3%) were from Taiwan, and 26 (17.3%) were from Hong Kong. Both homeland and gender were found to be important predictors of alcohol consumption. Those from mainland China drank less than those from either Taiwan or Hong Kong. it is concluded that cultural values play an important role in explaining drinking among the Chinese. PMID- 8204676 TI - Predictors of intoxicated sex in injecting drug users. AB - Transmission of HIV by sexual contact as well as through sharing of contaminated injection equipment is a source of viral spread from injecting drug users (IDUs). We report on an analysis of data from 1,245 IDUs interviewed in Sydney, Australia in which half of the respondents reported being intoxicated during sex for more than half of their sexual encounters. The most common drugs on which people were intoxicated during sex were heroin, cannabis and alcohol. Predictors of having sex when intoxicated were a lower likelihood of having been in treatment, higher number of sexual partners, sharing injection equipment with more people and more recently, being intoxicated when injecting, and not being a sex worker. The data indicate that having sex while intoxicated is common in these IDUs and that sex under the influence of drugs is part of a more general lifestyle of spending a greater time intoxicated. Targeting of those IDUs who spend a significant amount of time intoxicated and their recruitment into treatment may thus reduce both risky sexual behaviour and risky injecting behaviour. PMID- 8204677 TI - The adequacy of screening, documenting, and treating the diseases of substance abuse. AB - In a large inner-city teaching hospital, only 28 percent of over 1000 consecutive hospital admissions received proper screening for diseases of substance abuse. Although the CAGE questions are currently considered the best screening test for quickly assessing an alcohol abuse history, not a single CAGE question was documented during our 23 day study. Of the 1010 patients in the study, 160 or 16% were found to be substance abusers. Of these, 57 (37%) were properly screened by the physician team and 8 (5%) received adequate follow-up treatment for their substance abuse by way of social service or psychiatric consultation, or documented counselling by their physician. Physicians are not adequately screening for the diseases of substance abuse, and are not appropriately evaluating and referring patients who are known to be substance abusers. Meaningful training of medical students and physicians is necessary to increase awareness and produce positive behavior change. PMID- 8204678 TI - Reduction of psychopathology among individuals participating in non-treatment drug abuse residential studies. AB - The psychological repercussions in drug abusing individuals of their participation in non-treatment residential drug abuse research protocols have been uncertain. To study this, the average raw scores of the Symptom-Check List 90 Revised (SCL-90R) at the time of recruiting and discharge (40.2 +/- 15.6 days later) was studied at the Addiction Research Center of the National Institute on Drug Abuse (NIDA-ARC), in Baltimore, Maryland, in a sample of 233 drug abusers seeking no treatment. There was significant reduction in symptomatology (p < .01) between recruiting and discharge for Obsessive-Compulsive, Interpersonal Sensitivity, Depression, Phobic Anxiety, Paranoid Ideation, Psychoticism, and Total Scores. These findings suggest that participation of drug abusers in non treatment residential studies is safe and may improve their psychological status, which may be a therapeutic outcome of disengaging individuals from their drug environment and offering a safe and structured milieu. PMID- 8204679 TI - Operant rate depressant effects of ethanol in mice selectively bred for differential neurosensitivity to ethanol. AB - Few studies have investigated genetic differences in the effects of ethanol on operant schedule-controlled behaviors. The use of genetically defined populations in sensitive measures of complex behavior can help determine genetically covarying responses to ethanol as well as environmental contexts important for demonstrating genetic differences. The purpose of the present study was to investigate the rate depressant effects of ethanol on two lines of mice selectively bred for increased, LS/Ibg (LS), and decreased, SS/Ibg (SS), sensitivity to the acute narcotic effects of ethanol. Ethanol dose-dependently decreased high rates of behavior maintained by fixed ratio responding for water in both the LS and SS mice. Interestingly, the LS and SS mice did not differ in the rate depressant effects of ethanol under these conditions despite the sensitivity of this measure to the CNS effects of drugs and the very large differences between these lines in sensitivity to numerous other ethanol-related effects. While the SS mice were slightly less sensitive, and LS mice tended to show a low dose rate increasing effect, none of the differences were significant as ED50 values for rate depression differed by only 2.5 percent. The results of this experiment demonstrate that sensitivity to the effects of ethanol on fixed ratio responding for water is not genetically related to the acute narcotic effects of ethanol. In addition, the findings show that previously reported differences in operant ethanol self-administration between these two lines of mice are not due to differential sensitivity to the direct effects of ethanol on reinforced behavior. PMID- 8204680 TI - Clonazepam prescribing patterns and abuse by methadone patients in a medical center setting. AB - Methadone patients who require inhospital detoxification from self-administered clonazepam (CZM) were interviewed. Patients enrolled in drug dependency (DDTP), combined addiction psychiatry (CAPP) and methadone maintenance (MM) were surveyed. Twenty out of 20 DDTP and 15 out of 30 CAPP patients responded indicating no knowledge of CZM as a drug of abuse. MM patients were reluctant to respond, but the 18 out of 72 who did, indicated knowledge of CZM abuse. Ten identified CZM as a "downer," 11 indicated its use to "get high," 10 knew other people who abused, and 6 believed abuse to be common. Six identified a street value as $1-5 per mg and 5 identified the amount to get high as 2 mg or more. A 90 day monitoring of prescription writing by all physicians at the same institution used a threshold of benzodiazepine potency equivalent to 40 mg diazepam daily with unmonitored refills. Using this arbitrary descriptor of potentially hazardous prescribing, CZM was the most commonly "excessively" prescribed benzodiazepine. (Fifty cases out of 194 prescriptions as compared to 14 cases of all other benzodiazepines combined.) Psychiatrists wrote 68%, neurologists 15% and internists 14%. As a result of this information, physicians are cautioned and prescription monitoring mechanisms are recommended. PMID- 8204681 TI - Identification of proteins in polyacrylamide gels by mass spectrometric peptide mapping combined with database search. AB - Mass spectrometric peptide mapping of proteins separated by one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis has been investigated. The best results are obtained after blotting of the proteins onto polyvinylidene difluoride membranes followed by enzymatic digestion of the protein on the membrane. The peptide maps were investigated in terms of completeness and applicability for protein identification using a previously developed database search program as well as for the possibility for full characterization of covalent modifications in the proteins. The most complete peptide maps were obtained when the proteins were reduced and alkylated on the membrane prior to enzymatic digestion followed by separation of the resulting mixture by high performance liquid chromatography prior to mass spectrometric analysis. Such peptide maps cover up to 98% of the sequence and consequently may allow complete characterization of post-translational modifications in proteins for which the amino acid sequence is known. The fastest and most sensitive procedure to obtain peptide maps sufficient for protein identification was direct analysis of the extracted peptide mixture by matrix-assisted laser desorption ionization (MALDI) mass spectrometry. The use of external and internal calibration of MALDI spectra for database searches is evaluated as well as the possibility of including a post calibration routine within the search program. PMID- 8204682 TI - Analysis of a bioactive synthetic analogue of tuftsin by tandem mass spectrometry: anomalous fast atom bombardment activated processes. AB - Fast atom bombardment (FAB) tandem mass spectrometry has been used to analyse the biologically potent, partially modified retro-inverso (PMRI) synthetic isomer of tuftsin: this compound represents the active peptide of the fraction of gamma globulin (leukokinin) which binds specifically to blood neutrophilic leukocytes and monocytes. Protonated molecules and fragment ions were collisionally dissociated at low energies in a triple-quadrupole mass spectrometer to yield a complete picture of the reactions that occur in the condensed and in the gas phase. The study shows that, when retro-inversion is within the N-terminal amino acid, charge localization at the basic sites (possibly at the N-terminus) induces a marked decomposition of the molecule, the loss of ammonia being the most favourable fragmentation process. Also, artifacts are formed in the liquid phase via bimolecular reactions promoted by the high-energy beam. The findings indicate that despite the fact that PMRI isomers of this type are stable against exo peptidases and also stable under acidic conditions, they appear to be labile under conditions where the energy deposition, due to FAB is necessarily high. PMID- 8204683 TI - Electrospray mass spectrometric characterization of the components of protein mixtures and its application to members of the chemokine family of interleukins. AB - Electrospray mass spectrometry has been employed to detect and characterize the members of a closely related family of immunologically active proteins (chemokines) produced in cell culture by stimulated fibroblasts. The reliability of the method to produce precise data concerning the relative proportions of proteins present in mixtures was investigated in a model system and found to be satisfactory in a range of 10:1 in concentration. PMID- 8204684 TI - Studies of non-covalent interactions of actinomycin D with single-stranded oligodeoxynucleotides by ion spray mass spectrometry and tandem mass spectrometry. AB - Non-covalent binding of actinomycin D (AMD) to single-stranded DNA (ssDNA) was observed by ion spray mass spectrometry. Interactions between AMD and different sequences of non-self-complementary oligodeoxynucleotides were investigated as a function of pH. Non-covalent AMD/ssDNA complexes disappeared at low pH, and no ssDNA complexes were detected with rifampicin (RP). Moreover, the different binding affinities between AMD and ssDNA with and without 5'G-C3' or 5'C-G3' base sequences were also demonstrated using ion spray mass spectrometry. Additional support for the non-covalent nature of binding in AMD/ssDNA complexes was obtained from tandem mass spectrometry. PMID- 8204685 TI - Application of electrospray and fast atom bombardment mass spectrometry to the identification of post-translational and other chemical modifications of proteins and peptides. AB - Mass spectrometry is a very powerful tool in the identification of chemical modifications of proteins and peptides. Often these modifications cannot be determined by conventional techniques. This report describes the combined use of electrospray ionization mass spectrometry and fast atom bombardment mass spectrometry to complete the primary structure of proteins and peptides. Examples illustrate how mass spectrometry is used to locate sites of phosphorylation, methylation and acetylation, and identify blocking groups and unexpected side reactions such as deamidation or alkylation. PMID- 8204686 TI - Enrichment of selected serum fatty acids after a small oral dosage of (1-13C)- and (8-13C)triolein in human volunteers analysed by gas chromatography/combustion isotope ratio mass spectrometry. AB - In this study the fate of 100 mg orally administered (1-13C)- and (8-13C)triolein was traced in the serum lipids of four healthy human subjects. After an overnight fast the subjects consumed hourly meals of a liquid formula diet over 12 h. Ninety minutes after the first meal in the first study (1-13C)triolein was given and in the repeat study the same subject received (8-13C)triolein. Triacylglycerol (TG), phospholipid (PL) and cholesterol ester (CE) were isolated from serum sampled prior to and in intervals after isotope administration. Fatty acid composition of serum lipids was measured using gas chromatography/mass spectrometry. 13C enrichment in palmitic, stearic, oleic and linoleic acids of these fractions was determined by gas chromatography/isotope ratio mass spectrometry. With (8-13C)triolein a significantly higher enrichment (peak +17.1 +/- 14.3/1000 delta 13C) was found in the oleic acid of TG fraction than with (1 13C)triolein (peak -7.1 +/- 4.2/1000), which may be due to a faster elimination of (1-13C)oleic acid from serum TG. 13C enrichments in the other fatty acids of the TG fraction as well as of PL and CE fractions were in the range of natural 13C abundance (-25 to -32/1000). PMID- 8204687 TI - Leukemia. PMID- 8204688 TI - Immunotherapy for acute leukemias. AB - Successful immunotherapy for cancer and, in particular, monoclonal antibody-based therapy are most likely to succeed first for the hematopoietic neoplasms because of their biology and because of the pharmacology of monoclonal antibodies. Ten years of steady development in the field, including identification of better antigen-antibody systems, genetic engineering of humanized monoclonal antibodies, construction of new toxin and radionuclide conjugates, and better understanding of the interactions of monoclonal antibodies with cytokines, eg, interleukin-2, has led to a series of recent trials showing significant activity of monoclonal antibodies in leukemias. This activity encompasses the ablation of large masses of cells prior to bone marrow transplantation, as well as the elimination of minimal disease in vivo and ex vivo. PMID- 8204689 TI - Cytogenetics and oncogenes in leukemia. AB - Analysis of chromosomal abnormalities present in the malignant cells of patients with leukemia has provided much information of diagnostic and prognostic importance. The cloning of genes rearranged by translocation breakpoints has provided insights into both the regulation of normal cell growth and differentiation and the pathogenesis of human malignancies. This article reviews recent analyses of the association of specific karyotypic changes with other disease characteristics, including treatment outcome. Also covered is the substantial progress that has been made in the molecular analysis of genetic abnormalities in leukemia, with emphasis on those changes produced by chromosomal rearrangements. The use of information derived from these latter studies to develop polymerase chain reaction and fluorescent in situ hybridization assays for clinical use is also summarized. PMID- 8204690 TI - Myelodysplasia. AB - Myelodysplasia or myelodysplastic syndromes represent a heterogeneous group of bone marrow disorders characterized by dysmaturation, cytopenias, and a propensity for leukemic transformation. Although universally adopted, the French American-British classification still has several limitations and an inability to categorize all patients. Refinements in morphologic and histologic interpretation in addition to the use of scoring systems may improve diagnostic and prognostic capability. Cytogenetics and molecular genetic abnormalities are providing clues to the fundamental pathogenesis of myelodysplastic syndromes. However, the lesions responsible for initiation or disease progression are as yet unresolved. Although chemotherapy and allogeneic transplantation may be used in selected patients, the mainstay of therapy remains supportive care, with differentiating therapy being largely disappointing so far and the role of hematopoietic growth factors remaining unresolved. PMID- 8204691 TI - Endocrine tumors: molecular biology at the bedside? PMID- 8204692 TI - Pituitary adenomas. AB - Recent advances in the management of pituitary tumors have included diagnostic tests that approach 100% sensitivity and specificity. Although pharmacologic agents with greater specificity and, therefore, greater therapeutic efficacy have been developed, transsphenoidal surgery with microneurosurgical technique remains the primary means of treating these tumors. Stereotactic radiosurgery, which serves to either augment or supersede surgical management, has shown great promise as possibly a curative treatment for these tumors. This technology has been enhanced by the advent of magnetic resonance imaging stereotactic localization, which can accurately visualize small microadenomas as well as the optic apparatus. Further follow-up is necessary to assess the long-term tumor control rate, endocrinologic effects, and postradiosurgery morbidity, which may include hypopituitarism and delayed-onset optic neuropathy. PMID- 8204693 TI - Diagnosis and management of thyroid malignancies. AB - Although thyroid nodules occur quite frequently, thyroid carcinoma is a relatively infrequent malignancy. Fine needle aspiration has proven to be the most efficient, most accurate diagnostic procedure in the management of nodular thyroid disease, and it has significantly improved the selection of patients for surgery. Although there is still some controversy, most authors advocate total thyroidectomy for differentiated thyroid carcinoma. This treatment strategy facilitates detection of recurrence with 131I and allows for more effective treatment of recurrent disease. Several novel prognostic markers are being investigated to help identify the most aggressive thyroid malignancies and thus aid in the overall treatment of patients with these tumors. PMID- 8204694 TI - Endocrine tumors of the gastrointestinal tract. AB - Endocrine tumors of the gastrointestinal tract are among the most interesting and heterogeneous of human malignancies. Presenting in highly variable fashions, carcinoid tumors and pancreatic endocrine tumors share natural histories that may range from the serendipitously found, easily cured appendiceal carcinoid to the highly malignant pancreatic islet cell tumors associated with unique endocrine syndromes. The heterogeneity and the relative rarity of these tumors hinder both basic and clinical research. However, new concepts of tumor biology, diagnosis, and treatment are emerging, which will lead to better understanding of the behavior of these tumors and, ultimately, to better treatment of the individual patient. PMID- 8204695 TI - Growth factor balance and tumor progression. AB - The role of balance of negative and positive autocrine growth factors in malignant progression is reviewed with an emphasis on transforming growth factor alpha (TGF-alpha) as a stimulating factor and transforming growth factor beta (TGF-beta) as an inhibiting factor. Evidence suggests that in normal cells TGF alpha is down regulated in non-dividing or quiescent states in vitro. Tumor cells which have early stage characteristics as represented by poor clonal growth and poor tumorigenicity in athymic mice also show repression of TGF-alpha in non dividing states. Progression of this phenotype is induced by uncontrolled low level expression of TGF-alpha by transfection with a constitutive expression vector for the polypeptide. Transfection of the unprogressed phenotype with a constitutive anti-sense vector for TGF-beta, also leads to tumor progression by repressing the autocrine negative TGF-beta activity normally expressed by these cells. Both the upregulation of TGF-alpha and the repression of TGF-beta generated in vivo progression without changing growth rates in vitro. Instead, clonality and ability to reenter the cell cycle from quiescence were increased. Thus, it is concluded that an autocrine balance of positive and negative factors is important for maintaining controlled re-entry into dividing states from non dividing states and that disruption of this balance leads to malignant progression characterized by greater independence of the malignant cells from the control of exogenous growth factors. PMID- 8204696 TI - Advances and controversies in the study of programmed cell death/apoptosis in the development of and therapy for cancer. AB - Whether normal or malignant, cells possess within their repertoire of epigenetic programs the ability to undergo a process of cellular suicide, termed programmed cell death. This programmed cell death process involves an epigenetic reprogramming of the cell that results in an energy-dependent cascade of biochemical and morphologic changes within the cell (also termed apoptosis), resulting in its death and elimination. Activation of programmed cell death is controlled by a series of endogenous cell-type-specific signals. In addition, various exogenous cell-damaging treatments (eg, radiation, chemicals, and viruses) can activate this pathway if sufficient injury to the cell occurs. PMID- 8204697 TI - Biologic functions of the genes responsible for familial cancer. AB - Clinical and molecular genetic studies on human familial cancers have provided important information toward further understanding of the etiology of hereditary and sporadic cancer. Our next challenge is to determine how mutations involving this group of genes leads to functional changes in the cell causing malignant growth. This article summarizes some of the significant findings recently reported concerning the biologic function of the genes that are involved in hereditary cancer syndromes. PMID- 8204698 TI - Gene therapeutics and gene therapy for cancer. AB - Recent advances in molecular biology have opened new avenues of basic genetic engineering technology and have made possible the application of this technology in clinical human gene therapy. Replication-defective viral vectors and biocompatible materials, eg, liposomes, have been developed as vehicles to introduce potentially therapeutic genes into mammalian cells. Over the past 2 years, this technology has increased the possibilities for therapy in numerous genetic diseases. Approaches at the molecular level have also demonstrated that one of the mechanisms of human cancer development is overexpression of dominant oncogenes, expression of mutant oncogenes, or specific chromosomal deletions or mutations that induce inactivation of tumor-suppressor activity. This concept suggests that the introduction of antisense oncogenes and wild-type tumor suppressor genes, eg, p53, could halt or reverse these mechanisms, thus having a therapeutic effect in cancer. Moreover, evidence that the immune system is capable of eliminating tumor cells in numerous animal models has suggested gene therapy approaches for the delivery of cytokines, which promote the activation of cytotoxic immune responses against the malignant tissue. The efficacy of these gene therapy protocols is now being evaluated in both animal model systems and clinical trials. This article reviews recent highlights in this rapidly evolving field. PMID- 8204699 TI - [Specific IgE in the gastric and duodenal mucosa. An epiphenomenon or pathogenetic mechanism of some forms of "peptic" ulcer?]. AB - Allergic mechanisms have been shown to induce gastric and intestinal damage in animal models. It has been demonstrated that people allergic to food may complain of gastrointestinal disorders. Furthermore food allergens can induce gastric mucosal damage in sensitized people. Little is known as regards allergic mechanisms underlying "peptic" ulcers although there are reports suggesting that some forms of gastric and duodenal ulcer may be caused by allergy. AIM. Of the study was to evidence if IgE specific to food and inhalants are localized in gastric and duodenal mucosa and if the in vitro incubation of gastric and duodenal biopsies with specific allergens, stimulate mast-cell mediators. MATERIALS AND METHODS. Twenty-one patients affected by gastric/duodenal ulcers (14 with high total IgE serum levels) and 16 controls were studied. All patients were submitted to upper digestive endoscopy and biopsies were taken from gastric fundus, body and antrum and duodenal bulb. Specific IgE to food and inhalant allergens were tested after homogenization of biopsies, using commercial kits. In 3 selected patients, 3 biopsies from gastric fundus and 3 from duodenal bulb were taken. After incubation of mucosal of mucosal biopsies with allergens (wheat, lactoalbumin, Parietaria J. pollen), the release of histamine and tryptase was measured. The release of Pepsinogen A was measured in the same conditions, as control. RESULTS. Specific IgE to food and inhalants allergens have been found in 164/586 tests (27.9%) of "peptic" ulcer patients and in 17/430 tests (4%) of controls. The duodenal bulb resulted the site in which most frequently IgE have been found. The release of histamine and tryptase has been stimulated only in 1/6 tests by incubation of biopsies with specific allergens in patients with specific IgE. PG-A release has been always stimulated by incubation of gastric biopsies, but not duodenal biopsies, with all tested allergens. DISCUSSION AND CONCLUSION. Specific IgE may be localized in gastric and duodenal mucosa of patients with "peptic" ulcer and/or food allergy. This event is linked to high total IgE serum levels and in a lesser extent, intestinal parasitosis, it is not strictly correlated with specific IgE in the serum and it regards both food and inhalant allergens. No relevant effects were observed after incubation of specific allergens with gastric or duodenal mucosa biopsies containing specific IgE. The possibility that higher allergens concentration stimulate mediator release from mast cells should be investigated. A defect of the gastric or duodenal epithelial barrier which permit a passage way for proteins with subsequent IgE production in the submucosa, appears to be the cause of localization of specific IgE in stomach and duodenum. PMID- 8204700 TI - [Ulcerative rectocolitis diagnosed in the elderly. Case studies]. AB - Fourteen patients with idiopathic ulcerative colitis (UC) diagnosis made over 60 years of age have been extrapolated from 255 (5.49%) consecutive. Some clinical parameters (sex; symptoms of onset; delay in diagnosis; extension of disease; density of relapses; therapy with cortisone) have been compared between the 14 patients with ultra sixtieth year of age diagnosis (A group) and the 241 patients with a diagnosis made previously (B group). There were no significant differences concerning the symptoms at onset and the delay in diagnosis. In group A a larger prevalence of the male (M/F 3.66 against 1.46) and distal localization (64% against 53%) have been reported. The density of relapse and therapy with cortisone (p < 0.025) prevailed in B group. In conclusion, limited to our experience, the UC in A group is less severe than in B group. PMID- 8204701 TI - [Total parenteral nutrition in critical patients. The metabolic-nutritional aspects and effects on immune function of 2 different isocaloric-isonitrogenous regimens]. AB - The aim of this investigation was to compare, in a randomized short-term study the effects on some parameters evaluating lipid metabolism, nutritional status and immune function of two different patients. Particularly, the influence of the intravenous (i.v.) infusion of a fat emulsion on above-mentioned parameters was evaluated. The two regimens (G and GL) were isocaloric (about 30 kcal.kg-1.d-1 non protein energy) and isonitrogenous (about 0.27 g.kg-1.d-1 nitrogen); the only difference was the source of non-protein calories administered. Regimen G consisted of glucose-based TPN (100% of non-protein energy as glucose) whereas, in regimen GL (glucose-lipid-based TPN), the 55% of non-protein caloric supply was given as glucose and 45% as lipids. 9 of the patients were randomly assigned to receive regimen GL (group GL) and 8 to receive regimen G (group G). TPN was delivered through a central vein catheter for 8 days; during this period no hepatic or metabolic complications have been observed. Clinical and laboratory tests were performed at day 0 (enrollment), at day 4 (after 4 days of TPN) and at day 8 (at the end of TPN). Both regimens of TPN were able to induce an improvement of the nutritional status and serum prealbumin (TBPA) significantly increased in all patients (p < 0.05). The results of the immune measurements showed that no significant change in immune function during the administration of either regimen occurred. However, in group GL, we observed a slight, non significant change in the percentage numbers of T-cells subpopulations that resulted in a decrease in the ratio of helper to suppressor T-cells (H:S). Serum lipids and lipoprotein profile didn't change significantly in group GL. On the contrary, in group G, we observed a significant decrease in serum concentrations of HDL cholesterol (p < 0.05), LDL cholesterol and apo A1 (p < 0.01) while total cholesterol remained unchanged; a non significant rise in serum triglyceride also occurred, These results show that the two regimens had a similar impact on nutritional status in both groups. The i.v. infusion of the fat emulsion didn't alter lipid profile and was not associated with an impairment of some aspects of the immune function. In conclusion, our results confirm that fat emulsions represent an important component of i.v. nutritional support regimens and should continue to be used when and where indicated in short-term TPN. However, long term effects of i.v. infusion of fat emulsions on the immune systems should be further investigated, in a more substantial number of patients. PMID- 8204702 TI - [The psychological characteristics of dyspepsia. A controlled study with gastroscopic follow-up]. AB - It's known that some psychologic factors could be implicated in dyspepsia. Therefore, the psychologic aspects of 38 dyspeptic patients (17 males, 21 females, aged 18-65 years), who underwent digestive endoscopy, were evaluated by means of Rorschach and MMPI test. Patients with previous peptic ulcer history, with chronic ethanol or NSAID intake, operated on digestive tract and patients with behavioural problems were excluded. The results of psychological tests enhanced two main groups: anxiety patterns (17 patients--49%) and normal patterns (21 patients--55%). Endoscopic and histological findings moreover showed: "anxious" group--12 patients with chronic gastritis (HP+ 50%), 5 patients with normal endoscopy; "normal" group--16 patients with chronic gastritis (HP+ 87.5%), 5 patients with normal endoscopy. This study suggests that in about 50% of dyspeptic patients anxious pattern is present. Moreover chronic gastritis is more frequently associated to Helicobacter pylori in non-anxious patients. PMID- 8204703 TI - [The effect of ursodeoxycholic acid in patients with liver cirrhosis and chronic hypertransaminasemia]. AB - The aim of the study was to evaluate the effect of ursodeoxycholic acid (UDCA) oral administration on alanine aminotransferases (ALT) levels in cirrhotic patients with chronic hypertransaminasemia. Ninety consecutive patients with histologically proven liver cirrhosis and ALT levels higher than twice the upper limit of normal for at least six months, were admitted to the study. All the patients were treated with UDCA 10 mg/kg/day for one year. At the end of this period they were randomized to placebo or to continue UDCA therapy for three further months. ALT levels were evaluated before the beginning of UDCA therapy, at twelve and fifteen months by standard methods. After 12 months of UDCA, ALT decreased significantly (-39 UI, 95% confidence intervals -27 to -52 UI). At the 15 th month ALT did not vary with respect to its values at the 12th month in 36 patients randomized to continue UDCA, while it increased significantly in patients taking the placebo (+11 UI 95% confidence intervals +2 to +19). The results of this study suggest that UDCA is effective in controlling the biochemical activity of the liver disease in cirrhotic patients. PMID- 8204704 TI - [Chronic idiopathic intestinal pseudo-obstruction associated with volvulus of the transverse colon. The identical mode of clinical presentation and of the intestinal manometric pattern in monozygotic twins]. AB - Two monozygotic female twins with chronic idiopathic intestinal pseudo obstruction associated with transverse colon volvulus are described. Quite similar clinical events and temporal coincidences characterized the symptoms which has preceded and followed right colectomy undergone by both of them due to intestinal volvulus. The esophageal, gastroduodenal, colonic and anorectal manometric investigation revealed very similar alterations in both girls. Increased amplitude of distal contractions of the esophagus, a depressed fasting antro-duodenal motility, with absence into antrum and oro-aboral non-propagation in the duodenum of the phase III activity of the interdigestive motor complex were the main findings along with a state of pronounced colonic hypomotility and an hypoesthesia of the rectal ampulla to the volumetric stimulus. This report indicates the association between chronic intestinal pseudo-obstruction and transverse colon volvulus in monozygotic female twins, and it points out the rarity both of the specific symptomatic coincidences and the similar clinical events and of the almost absolute identity of the intestinal motor patterns. PMID- 8204706 TI - Public health in Australia: a personal reflection. PMID- 8204705 TI - [Azithromycin-omeprazole. Treatment for the eradication of Helicobacter pylori]. AB - AIM: To evaluate the benefit of 4-week regimen including azithromycin+omeprazole (vs omeprazole alone) for eradication of Helicobacter pylori. METHODS: Twenty HP positive patients with an ulcer dyspepsia (NUD) were included in this study. They were given either omeprazole 40 mg for 4 weeks alone or in combination with azithromycin 1 g/die for 1 week. Endoscopy was performed before 4 weeks after and 4 months after treatment. The presence of HP was assessed in antral and corporeal biopsies by urease test and histology. RESULTS: HP eradication was observed in 9/10 (90%) patients in the omeprazole+azithromycin group and 0/10 patients in the omeprazole alone group. CONCLUSION: Omeprazole 40 mg for 4 weeks in combination with azithromycin 1 g die for 1 week eradicates HP in 90% of these patients. The good eradication percentage and absence of collateral effect make us extend patients' number to test. PMID- 8204707 TI - Is there life after Foucault? Poststructuralism and the health social sciences. PMID- 8204708 TI - A cluster of cases: coincidence or cause for concern? PMID- 8204709 TI - A cluster of brain tumours in a New South Wales colliery: a problem in interpretation. AB - Following the reporting of a cluster of cases of brain tumour in the workforce of an underground coal mine (Mine A) in the Newcastle coalfield, a study was carried out to determine whether this phenomenon was due to chance alone or whether an environmental cause could be postulated. The study design was a historical cohort study over 15 years comparing the incidence of brain tumour (ICD9 191 and 192) in the index mine with that in two control mines (Mines B and C) in the same area and with that in the general Australian population. We compared environmental exposures (ionising and nonionizing radiation and chemical exposure) in the three mines. With Australian brain tumour incidence rates as reference, the standardised incidence ratio for brain tumour in Mine A was 5.3 (95 per cent confidence interval (CI) 1.08 to 14.04) and in Mines B and C combined was 1.23 (CI 0.02 to 3.80). On most environmental assessments the three mines were similar but Mine A used larger volumes of solvents than the other mines. This study poses two questions: was the increase in cases of brain tumour in Mine A 'real' and if so, was it related to the use of solvents? Data, from an investigation of a cluster such as this, are unlikely to be conclusive. Nevertheless, such answers are demanded not only by those at risk but also by the mine management, which is responsible for a safe working environment. Some of the difficulties involved with this judgment are discussed. PMID- 8204710 TI - Cardiovascular risk in adult Melbourne Chinese. AB - Chinese migrants have low cardiovascular mortality, particularly in their first 10 years of residence in Australia. The apparent increase in cardiovascular deaths among Asian migrants who have lived in Australia for more than 10 years suggests that cardiovascular risk transition may occur soon after migration. In this descriptive study, we found that Melbourne Chinese were not low in cardiovascular risk factors as usually defined. The prevalence of hyperlipidaemia (7.7 per cent for men and 5.2 per cent for women) was similar to the prevalence for other Australians (6.8 per cent for men and 4.4 per cent for women). In spite of low mean blood pressure (systolic blood pressure 114 +/- 23 mmHg (mean +/- standard deviation) and diastolic blood pressure 67.3 +/- 10.6 mmHg), Melbourne Chinese women were hypertensive as often as their Australian counterparts. The prevalence of cigarette smoking in men (26.9 per cent) was also comparable to prevalence for Australian males (24.1 per cent). Being slim is the only recognised cardiovascular protection that Melbourne Chinese may have. A high waist-to-hip ratio (0.91 +/- 0.054 for men and 0.88 +/- 0.077 for women), however, may outweigh the potential benefit of lower prevalence of overweight (17.7 per cent for men and 14.1 per cent for women). Melbourne Chinese men had a multiple risk-factor profile similar to their Australian counterparts. Differences in multiple risk factors in women were attributable to fewer Chinese women having a single risk factor (15.4 per cent versus 30.1 per cent).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204711 TI - Community worry about heart disease: a needs survey in the Coalfields and Newcastle areas of the Hunter region. AB - A needs survey was administered by mail in the Coalfields area of the Hunter region (a lower socioeconomic area around Cessnock) and in a higher socioeconomic area of Newcastle. The purpose was to assist planning for Coalfields Healthy Heartbeat--a community-action heart disease prevention program. Response rates from random samples of residents were 435/897 (49 per cent) for the Coalfields and 565/875 (65 per cent) for Newcastle. In both study areas heart attack was ranked eleventh from a list of 17 potential community worries, well below drugs, crime, road safety, the environment, cancer and 'loss of health'. Coalfields respondents were more worried about all issues on the list than were the residents in Newcastle and were less likely to have heard about recent health promotion campaigns. Coalfields respondents felt that heart disease prevention was the responsibility of the individual, the family, and the medical profession, in that order, and much less the responsibility of local community groups. Results suggest that health promotion strategies incorporating values, language and symbols that are meaningful to distinct subgroups may be more successful than disease-specific programs aimed at the general population. PMID- 8204712 TI - Food habits in Aborigines and persons of European descent of southeastern Australia. AB - As part of a study of risk factors for glucose intolerance and heart disease in Australian Aborigines and persons of European descent, we elicited the prevalence of food habits that may be associated with high fat and high salt intakes. Interview data were gathered from population-based samples in country towns and visitors to an Aboriginal health service in a state capital city, all in southeastern Australia. Among persons aged 13 years and over, the frequency of eating takeaway food as a meal was categorised as monthly or less, weekly, more than once per week, and daily or more often. The prevalence of eating such meals was higher among city Aborigines than those living in the country town; the prevalence was lowest among the country-town Europeans (chi 2 = 184, 6 df, P < 0.001). The prevalence of adding salt during cooking and food consumption was higher among Aborigines compared with Europeans. Among country-town Aboriginal males aged 35 or under, 25 of 40 (63 per cent) added salt to cooked food 'most of the time', compared with 66 of 185 (36 per cent) Europeans (chi 2 = 9.8, P = 0.002). Among Aboriginal females, 47 of 64 (64 per cent) were in the highest category of salt use, compared with 35 of 190 (18 per cent) of Europeans (chi 2 = 66.3, P < 0.001). About one-third of country-town Aboriginal males used dripping to fry food, but in the other ethnicity, gender and location groups, vegetable oil was the most frequent choice. The main differences in food habits were associated with ethnicity, rather than location.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204713 TI - Public hospital activity, expenditure and staffing levels for indigenous and nonindigenous settlements in remote Queensland. AB - Aborigines and Torres Strait Islanders who live in discrete communities have poor health. Their life expectancy is relatively low and the underlying rates of morbidity, mortality and hospitalisation are much higher than the Australian average. For Aborigines and Torres Strait Islanders in the remote communities, the mortality rate is some three times higher than that of the total population. By comparing remote Aboriginal and Torres Strait Islander communities with similarly remote nonindigenous settlements, the paper shows that there was greater hospital activity per person in remote Aboriginal and Torres Strait Islander communities. Paradoxically, whereas there was greater hospital activity in discrete indigenous communities, there was lower expenditure per person on hospital services. The paper finds also that there were fewer medical and nursing staff per person in remote Aboriginal and Torres Strait communities. PMID- 8204714 TI - Acute hepatitis B infection in aboriginal Australians. AB - The apparent incidence of acute hepatitis B infection in the Top End of the Northern Territory was estimated from notification data and hospital data to be 12 per 100,000 per year, with a marked difference between Aborigines (42 per 100,000) and non-Aborigines (4 per 100,000), and an odds ratio of 9.7 (95 per cent confidence intervals 3 to 33). Sixty percent of Aboriginal cases of acute hepatitis B occurred in children under 10 years of age, whereas non-Aboriginal cases occurred in adults aged 20 to 29, most with behavioural risk factors. These findings confirm the importance of immunising Aboriginal children to reduce the future incidence of hepatitis B infection and hepatoma. PMID- 8204715 TI - Falling incidence of HIV infection in a cohort of clinic attenders. AB - It is widely accepted that changes in sexual behaviour in the mid-1980s drastically reduced the spread of human immunodeficiency virus (HIV) through male homosexual contact in Western countries, but documentation of changes in infection rates has been based on observation of subjects enrolled in cohort studies, who may be highly selected and motivated. In this study, the incidence of HIV seroconversion was investigated among people attending a major site of HIV testing, counselling and patient care in Sydney. Over the period March 1985 to June 1990, 2,301 people were tested for HIV antibody on more than one occasion, following a negative result at the first test. On the basis of subsequent tests, 107 were found to have seroconverted during the study period, including 91 men who reported homosexual or bisexual contact as their only exposure to HIV. Overall, the incidence rate of HIV infection among men reporting homosexual or bisexual contact was 404 per 100 person-years of follow-up. Under various methods of calculation, the incidence was estimated to have declined between 1985 and 1989-1990. However, there was continuing HIV seroconversion in 1989-1990 and no indication of declining incidence in younger men. The fall in HIV incidence documented in this study supports the role of HIV prevention programs aimed at homosexual and bisexual men. PMID- 8204716 TI - Blood alcohol levels of patrons leaving licensed premises in Perth, Western Australia. AB - We aimed to determine the alcohol consumption, blood alcohol levels (BALs) and subsequent driving of patrons leaving 15 hotels and taverns in Perth, Western Australia. Of the 414 patrons approached by interviewers on Friday and Saturday evenings, 307 (74 per cent) consented to take part. Self-reported alcohol consumption, driving intentions, perceived levels of fitness to drive and demographic information were collected using an interviewer-administered questionnaire. Observations of subsequent driving were recorded and BALs were measured by breath-alcohol meter. The patrons surveyed were predominantly male (76 per cent) and aged between 18 and 35 (87 per cent). Average reported alcohol consumption was 7.6 standard drinks for males and 4.9 drinks for females, around double the daily amount recommended by the National Health and Medical Research Council. Further, 23 per cent of the sample had consumed more than 10 drinks (male) and 6 drinks (female). With respect to BALs, 37 per cent of patrons exceeded the drink-drive limit then in force of 0.087 and 56 per cent exceeded 0.05. Of greater concern, 23 per cent who were over the 0.08 legal limit were subsequently observed to drive even though they had been informed of their BAL and legal status with respect to driving. The results suggest that most young patrons drinking in Perth metropolitan hotels and taverns consume alcohol on such occasions in excess of limits currently recommended by health authorities and attain blood alcohol levels dangerous for driving. This is likely to remain unchanged without public debate as to the responsibility of licensees in serving a potentially harmful psychotropic drug and effective enforcement of liquor licensing laws. PMID- 8204717 TI - Tobacco in Western Australia: patterns of smoking among adults from 1974 to 1991. AB - Patterns of smoking in Western Australia since 1974 were examined using four data sets. Consistency between sets of data was high for adults in the various categories of smoker status. Having established consistency, the patterns revealed by the surveys conducted by the Health Department of Western Australia were examined in more detail. According to these data, prevalence fell from 31.2 per cent in 1984 to 23.9 per cent in 1991 but was still higher among males, at 27.3 per cent, than among females, at 23.4 per cent. Although the sex-specific prevalence levels were converging, the difference was still significant (P = 0.01). While patterns of smoking in Western Australia generally reflected those in Australia as a whole, some differences were detected. The variation in prevalence according to level of education among women became less pronounced: in 1991, prevalence was 25.5 per cent among women who had completed an apprenticeship or trade certificate compared with 21.7 per cent among women who had undertaken some university studies, the corresponding figures for 1984 being 31.1 per cent and 24.8 per cent. Differences in prevalence among young women between state and national data were also noted. Between 1987 and 1991 the prevalence of smoking among women in the 20- to 24-year age group decreased from 41.2 per cent to 29.0 per cent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204718 TI - Risks of premature death from smoking in 15-year-old Australians. AB - This cross-sectional actuarial analysis of 1990 mortality data aimed to estimate absolute risk of premature death from all causes, and from lung cancer, ischaemic heart disease and chronic bronchitis/emphysema due to tobacco smoking in the Australian population, and to estimate the number of current 15-year-old smokers in the 1990 Australian population who will die prematurely due to smoking. Competing risks were allowed for in the calculations. In males, conditional life expectancy for 15-year-olds was 78.0 years in nonsmokers, 73.3 years in ever smokers, and 71.5 years in smokers of more than one packet a day. For 15-year-old females, life expectancy was 82.0 years in nonsmokers, 78.4 years in ever smokers, and 76.9 years in smokers of more than one packet a day. The risk of premature death due to smoking in ever-smokers was estimated as 14.6 per cent in males (before 75 years) and 11.9 per cent in females (before 80 years), with lung cancer (male: 4.2 per cent; female: 3.4 per cent), ischaemic heart disease (male: 3.7 per cent; female: 1.7 per cent) and chronic bronchitis/emphysema (male: 2.4 per cent; female: 2.5 per cent) as the major contributors. From one year of 15 year-old male smokers (26,713), 3,916 premature deaths due to tobacco can be expected; this includes 1,106 lung cancer deaths, 991 ischaemic heart disease deaths and 641 chronic bronchitis/emphysema deaths. From one year of 15-year-old female smokers (32,355), 3,861 premature deaths can be expected; this includes 1,086 lung cancer deaths, 559 ischaemic heart disease deaths and 798 chronic bronchitis/emphysema deaths. PMID- 8204719 TI - Local injury information, community participation and injury reduction. AB - Better injury prevention is now a national health priority in Australia. Applying the health promotion strategies of the Ottawa Charter to injury prevention forms the basis of the World Health Organization's worldwide Safe Communities program. Taking such a community-focused approach has led to quantifiable reductions in injuries in several overseas countries, particularly in Scandinavia where falls of up to 30 per cent in particular injuries have been reported over a three-year period. In the Illawarra area of New South Wales, data from local hospital emergency departments have been used as the basis for a 'community information' strategy, in an attempt to replicate this overseas experience in an Australian setting. Reductions of 17 per cent in attendances by children for injuries (P < 0.001) and a 14 per cent fall in accident-related hospital admissions of children (not statistically significant) have been observed over the course of the four year intervention. Problems of community definition and external confounding influences outside the control of the project make it difficult to confirm a causal relationship. However, community information forms one important component in a comprehensive local injury-reduction strategy. PMID- 8204721 TI - Blood lead levels in children in Perth, Western Australia. AB - This study reports on an analysis of the lead concentrations in 123 venous blood samples collected from Perth children aged between two months and 17 years attending Princess Margaret Hospital. The overall geometric mean was 6.9 micrograms lead per 100 ml whole blood, with 95 per cent of results lying between 3.2 and 14.8 micrograms/100 ml. Among children under five years of age, those aged between 18 months and two years had the highest geometric mean blood lead (11.1 micrograms/100 ml). There were no consistent associations between geometric mean blood lead and area of residence, age group or sex. In this sample of Perth children, the mean blood lead concentration was lower than those reported in other studies. Less than 0.1 per cent of children of the age ranged studied would have been expected to have lead levels exceeding the NHMRC 'level of concern' (25 micrograms/100 ml) current at the time of the study. However, the recent adoption of goal of less than 10 micrograms/100 ml could mean that lead levels in up to 21 per cent of Perth children would now be regarded as excessive. PMID- 8204720 TI - Living near a lead smelter: an environmental health risk assessment in Boolaroo and Argenton, New South Wales. AB - This paper outlines a risk assessment of a lead-contaminated residential site in Lake Macquarie, New South Wales, near the Pasminco Metals-Sulphide lead and zinc smelter. The assessment includes a hazard identification and a dose-response assessment based on recent research findings; an exposure assessment based on two interrelated indicators, soil/dust lead and blood lead; a risk characterisation; and finally, a discussion of environmental and behavioural options for the management of risk. The exposure assessment showed lead concentrations of 20 to 21,460 parts per million in soil survey samples, 23 to 35,870 parts per million in household dust, and a range of mean values for blood lead concentration of 11 micrograms/dl to 17 micrograms/dl, in four study groups. The proportions of children within these groups having blood lead concentrations of 10 micrograms/dl or greater, the current level of known health effect, ranged from 57 per cent to 85 per cent. The decision by the National Health and Medical Research Council in June 1993 to set a goal for blood lead of below 10 micrograms/dl has important implications for the definition and the management of the environmental health risk from 'living with lead' in the area assessed. PMID- 8204722 TI - Is there a rural suicide problem? AB - Suggestions that youth suicide rates are disproportionately higher in rural areas were explored using Queensland cause-of-death data supplied by Queensland Health for the years 1986 to 1990. Standardised mortality ratios (SMRs) were compared across three zones: urban, provincial and rural, for three age bands: all ages, 15 to 19 years and 20 to 29 years, for each sex. This Queensland study did not find a statistically significant excess of rural youth suicides. Further study of this phenomenon involving other states is called for. PMID- 8204723 TI - Diffusion of new technologies to treat renal stones in Australia. AB - Several new therapies for treating renal stones developed since the 1980s have considerably reduced the use of open surgery and endoscopy for this condition. Extracorporeal shock wave lithotripsy (ESWL) has made the biggest impact. Assessment of ESWL in the early stages of its development assisted in rational introduction of the technology in Australia. However, this effect was short-lived and Australia would now appear to have a significant overcapacity in this technology. Use of ESWL in recent years indicates that distance is a major factor in reducing access to this technology. These observations raise several issues that need addressing, including the limited ability to avoid inappropriate proliferation of a technology, uneven distribution of ESWL units, difficulties of access and the effects of overcapacity upon indications and upon the cost effectiveness of a technology. PMID- 8204724 TI - Report from Lyon: nutrition and cancer. PMID- 8204725 TI - Report from Berlin: ninth AIDS conference--prevention. PMID- 8204726 TI - Child care for mildly sick children. PMID- 8204727 TI - Food consumption based on Australian dietary guidelines can cost less than traditional Australian diets. PMID- 8204728 TI - QALYs: a personal experience. PMID- 8204729 TI - Hepatitis B vaccination in New Zealand. PMID- 8204731 TI - International epidemiology. PMID- 8204730 TI - Footwear and falls in the elderly. PMID- 8204732 TI - Comparison of methods of cardiac output measurements determined by dye dilution, pulsed Doppler echocardiography and thermodilution in horses. AB - Cardiac output (CO) measurements by the three methods of dye dilution, pulsed Doppler echocardiography and thermodilution in horses under anesthetized conditions were compared. Although CO determined by the thermodilution method was slightly higher than those obtained by the other two methods, the measurements by all methods showed almost similar results. The coefficients of correlation between the dye dilution and thermodilution methods, the dye dilution and pulsed Doppler echocardiography methods, and the thermodilution and pulsed Doppler echocardiography methods were 0.87, 0.89, and 0.88, respectively (P < 0.01). These results indicate that pulsed Doppler echocardiography and thermodilution methods could be no less useful than the traditional dye dilution method for evaluating of CO in horses. The pulsed Doppler echocardiography method may offer some advantage over other two methods; it is non-invasive and enables continuous measurement of CO. PMID- 8204734 TI - Species-specific expression of the hepatic renin gene. AB - The catalytic reaction of renin, an aspartyl proteinase, with angiotensinogen is the rate-limiting step fo the renin-angiotensin system involved in the maintenance of blood pressure and electrolyte balance in mammals. We have characterized species-specific expression of the hepatic renin gene by RNase protection experiment, primer extension analysis, and promoter assay using an in vitro DNA transfection. RNase protection experiments revealed that the renin gene is expressed in rat liver, but neither in mouse nor in human. Primer extension analysis identified the putative promoter region of the rat renin gene, which contains TATAAAA sequence, a canonical regulatory DNA element. In order to test whether the upstream region of the renin gene with respect to the putative transcription initiation site is a functional promoter, we have examined the ability of the 5'-flanking sequences of the rat renin gene as well as the human and mouse genes to activate expression of a reporter gene containing the bacterial chloramphenicol acetyltransferase (CAT)-coding sequences, by transient transfection assays. In transfected HepG2 cells, a hepatoma cell line, only the rat renin promoter was capable of driving the CAT gene expression. These results suggested that the rat-specific renin gene expression in the liver could be primarily determined by its promoter specificity. PMID- 8204733 TI - Bioassay for interleukin-1, interleukin-6, and tumor necrosis factor-like activities in canine sera. AB - To measure interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-like activities in canine serum, bioassays were conducted using human melanoma A375S1, IL-6 dependent murine hybridoma MH60.BSF2, and WEHI 164 murine sarcoma subclone 28-4. Clinically normal adult beagles were experimentally induced endotoxic shock by an intravenous injection of lipopolysaccharide or local inflammation by an intramuscular injection of turpentine oil. IL-1-like activity was detected in sera from dogs with endotoxic shock. IL-6 and TNF-like activities were detected in sera from both dogs with endotoxic shock and local inflammation. IL-1-like activity in sera from the dogs with endotoxic shock declined after dilution with either medium or serum obtained before treatment (pre-serum), but the IL-1-like activity was maintained to a greater extent in samples diluted with pre-serum compared to those diluted with medium. TNF-like activity declined equally after dilution with either medium or pre-serum. On the other hand, IL-6-like activity was inhibited at low dilution. It was, therefore, necessary to dilute the serum samples to 1:180 from dogs with endotoxic shock or 1:60 from dogs with local inflammation, in order to minimize the effect of inhibitory factors on IL-6-like activity. IL-6-like activity was neutralized by monoclonal antibody against murine IL-6 receptors. TNF-like activity was neutralized by anti-mouse TNF alpha rabbit serum. However IL-1-like activity was not neutralized by either anti-mouse or anti-human IL-1 rabbit serum. PMID- 8204735 TI - Bioceramic implantation in the intermandibular space in bilateral rostral mandibulectomy of the dog. AB - Effect of bioceramic implantation on the intermandibular space along with plating in rostral mandibulectomy was investigated in the dog. In this group, bioceramic beads consisting of a complex of hydroxyapatite and tricalcium phosphate were implanted in the intermandibular space between the lingual surfaces of the fracture ends. In two other groups, the dogs received only plating on the ostectomized end, or they received only rostal mandibulectomy without plating. No difficulty in mastication was observed in the implanted group after surgery. In the dogs which received plating, however, difficulty was noted only in the 4th week when wet food was replaced by dry food, and in the control group in the 6th week after the surgery. From the radiological and microscopical findings, in dogs with only plating or without the fixation there was no bony union in the intermandibular space at 16 weeks, though the increase in fibrous tissue and bony callus in the area was much greater in the plated dogs than in the control group. In the implanted group, on the other hand, the increase in callus formation was considerable compared to the other groups. Moreover, the lingual surfaces of the fracture ends were well ossified at 12 postoperative weeks. This suggests that in canine bilateral rostral mandibulectomy the stabilization of the fracture ends with plates and bioceramic implants filling a gap in the intermandibular space may enhance the ossification between the fracture ends and prevent postoperative difficulty in mastication. PMID- 8204736 TI - Isolation and primary culture of bovine hepatocytes: albumin synthesis and adrenergic activation of glycogenolysis. AB - We describe a technique for isolation and primary culture of bovine hepatocytes, and their metabolic characterization. Hepatocytes were isolated from the caudate lobe of bovine liver by perfusion with 0.25 mM ethylene-glycol tetraacetic acid and 0.05% collagenase. The viability and yield of the cells were 70-92% and 0.1 3.6 x 10(7) cells/g liver, respectively. When the isolated hepatocytes were cultured in Williams' medium E, they began to spread in 3 hr and formed monolayers in 24 hr. These monolayers were retained for at least 6 days. To monitor the metabolic activities specific to liver, synthesis and secretion of albumin were measured by labeling with [35S]-methionine and immunoprecipitation. This activity was low in isolated hepatocytes, but increased after culturing 1-3 days, and decreased again after 6 days. Glycogenolytic activity was also assessed by measuring glucose release to the medium by stimulation with epinephrine. The glycogenolytic response to epinephrine was also enhanced by culturing the hepatocytes 1-3 days, but was decreased after 6 days. Since the isolated bovine hepatocytes retained the liver-specific activities of albumin synthesis and glycogenolysis for several days in culture, these cells are useful for cellular and molecular studies on the functions of bovine liver. PMID- 8204737 TI - Effect of change in body position on cardiopulmonary function and plasma cortisol in cattle. AB - The aim of these studies was to investigate the effect of body posture on circulatory and respiratory system function in unmediated cattle. The plasma cortisol concentration was also measured and served as an indication of the level of stress imposed by animal handling and positional manipulation. Six mature, healthy Holstein cows were physically restrained and studied in standing, supine and right lateral postures. The plasma cortisol concentration increased with the change in body position. In a supine position, the value was increased to more than three times the control value (p < 0.001). The arterial oxygen tension and oxygen saturation were significantly decreased (p < 0.001) with changes in body position. The decrease was most pronounced when cattle were restrained in a supine position. Arterial carbon dioxide tension, heart rate, mean arterial pressure and central venous pressure did not change significantly with changes in body posture. Restraining of cattle in a lateral recumbent or supine position without introducing anesthesia was found to exert a strong stress which affected the respiratory function and increased the plasma cortisol level. PMID- 8204738 TI - Pneumocystis carinii pneumonia in a thoroughbred foal. AB - Typical Pneumocystis carinii pneumonia was found in a male thoroughbred foal (46 days old) suffering from diarrhea and hypogammaglobulinemia after birth. The characteristics of the organisms were demonstrated by Grocott methenamine silver staining, and scanning and transmission electron microscopy. The present focal had no histological lesions suggesting immunodeficiency. However, he could not get adequate colostrum from his dam, because she died of hemorrhagic shock due to immuno-mediated thrombocytopenia at delivery. This condition was considered to have predisposed the foal to the pneumonia. PMID- 8204739 TI - Parasitism of Toxocara canis larvae in chickens inoculated with the ascarid eggs. AB - The distribution of T. canis larvae and pathological changes of the liver caused by them were studied in chickens inoculated orally with 1,500 embryonated eggs during 1 and 50 days after inoculation. The number of larvae recovered varied from 40 to 192 in the liver, 8 to 166 in the muscles, 0 to 4 in the heart, 0 to 2 in the spleen, 0 to 1 in the brain, respectively. Small white foci were observed on the surface of the liver since 6 days after inoculation. Histopathological examination of the liver revealed infiltrations of leukocytes and acidophilic cells, thickening of blood vessel and bile duct wall, and granulomatous nodules. The pathological changes become more remarkable in the later stage of inoculation. PMID- 8204740 TI - Identification of a Ca(2+)-dependent agarose-binding protein in chicken serum. AB - A Ca(2+)-dependent agarose-binding protein was purified from chicken serum by affinity chromatography on SeaKem agarose gels followed by gel filtration on Sephacryl S-300. Purified protein was eluted in a symmetrical peak at the position of molecular weight of 146,000. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, it was resolved into a single protein band with a molecular weight of 39,000 under nonreducing and of 41,000 under reducing conditions. Thus, the agarose-binding protein is suggested to be composed of noncovalently associated identical subunits which contain intrachain disulfide bonds. PMID- 8204741 TI - Immunohistochemical microquantitation method for type I collagen in kidney histological section of the rats. AB - An immunohistochemical micromethod for quantitation of type I collagen in frozen histological section of rat kidney was developed. A principle of this method is enzyme-linked immunosorbent assay (ELISA). The intensity of immunoreactivity of the section to an anti-type I collagen antibody was quantitated, and then the total protein content in the same section was measured colorimetrically. Type I collagen content was expressed as mg of type I collagen per g of total protein. In this micromethod, the minimum area and optimum thickness of the section were 5 mm2 and 10 microns, respectively. Type I collagen content in the rat kidney section was 3.02 +/- 0.12 mg/g. This method should be useful for diagnosis of renal failure. PMID- 8204742 TI - Role of lymphocytes in spontaneous regression of experimentally transplanted canine transmissible venereal sarcoma. AB - Sensitized peripheral blood lymphocytes (PBL) obtained from canine transmissible venereal sarcoma (CTVS)-regressed dogs were more cytotoxic against CTVS cells than non-sensitized PBL from untreated dogs. Cytotoxicity shown by sensitized PBL was inhibited significantly by the addition of anti-major histocompatibility complex (MHC) class II mouse monoclonal antibody as well as that of anti-dog thymocyte rabbit serum. The degree of cytotoxic activity shown by lymphokine activated killer (LAK) cells induced from non-sensitized or sensitized PBL was similar to that of the activity shown by sensitized PBL. These LAK activities were also prohibited by the addition of anti-dog thymocyte rabbit serum. Immunohistochemical examination demonstrated that MHC class II antigens were expressed on the surface membrane of CTVS cells and thymocyte antigens were detected on the surface of the tumor infiltrating lymphocytes. From the results mentioned above, lymphocytes which play a central role in tumor regression are considered to be T cells. These cells might recognize MHC class II antigens on the surface membrane of CTVS cells in tumor regression. PMID- 8204743 TI - Natural infection with attaching and effacing Escherichia coli (O15) in an adult cow. AB - A 19-month-old Holstein female manifested muco-hemorrhagic diarrhea. At necropsy, the colon contained a large amount of bloody material mixed with mucus and there was diffuse petechial hemorrhage on the mucosal surface. Histologic and electron microscopic examination of the colon revealed the characteristic lesion of attaching and effacing Escherichia coli (AEEC) infection. The organisms were associated with mucosal lesions and stained positively by an immunoperoxidase technique using antiserum to E. coli O group 15. Diarrhea caused by AEEC was recognized in this adult cow. PMID- 8204744 TI - Unilateral anophthalmia in a Holstein calf. AB - Unilateral anophthalmia in a Holstein calf was examined morphologically. On the left side, a small cystic remnant of the eye ball (CRE) was present in the orbit. The CRE was adhered to the dura mater through an abnormal foramen formed in the orbital region of the cranial base. At this region of the left cerebral hemisphere, a porencephalic change was detected. Histologically, the pigment epithelium was continued from the lining of the inner surface of CRE to the residual cerebrocortical tissue attached to the dura mater. These characteristic changes seem to suggest the partial fusion of the outer layer of the optic cup to the telencephalon during optic organogenesis. PMID- 8204745 TI - Ameloblastic fibro-odontoma in the mandibular incisor of a cow. AB - Odontogenic neoplasm was found in the mandibular incisor area of a 3-year-old Japanese black ox. Macroscopically, the cut surface was white and firm with streaks of hard tissue. Histologically, the tumor was composed of enamel organ structures with odontogenic hard tissue in fibromatous areas. It was diagnosed as ameloblastic fibro-odontoma. The absence of the 4th permanent incisor confirmed by radiography and microscopic examination strongly suggests that this tumor has been originated from the tooth germ tissues of the permanent left 4th incisor. PMID- 8204746 TI - Circadian oscillation of 64-kDa polypeptide in the rat suprachiasmatic nucleus. AB - In cell suspensions of suprachiasmatic nucleus harvested every 3 hr from rats kept under 12 hr: 12 hr light-dark cycle and constant darkness, we have detected a M(r) 64-kDa protein whose synthesis exhibits two distinct daily peaks in SDS PAGE. Analysis of densitometer tracings revealed that the synthesis of other proteins was independent of the time of day or not reproducible. Maximum synthesis of the 64-kDa polypeptide occurred at around CT6 and CT21, which are almost coincident with the phase advance regions of circadian activity rhythm induced by anisomycin and light pulses [15], respectively. These results suggest that the 64-kDa protein in SDS-PAGE may be a part of the circadian clock mechanism. PMID- 8204747 TI - Maceration of fetus in the Japanese serow (Capricornis crispus). AB - Out of 2,138 pregnant Japanese serows (Capricornis crispus), one case of the maceration of fetus was found in the winter of 1991, and examined pathologically. Because the fetus was covered with the hairs in the head and the neck regions, the fetus seemed to be implanted in the last breeding season and retained. The endometrium lacked the placentomes completely and showed metaplasia to the keratinized or non-keratinized squamous epithelium. In the non-keratinized region, the accumulation of neutrophils, eosinophils, lymphocytes, plasma cells and foreign giant cells was prominent in the subepithelial connective tissue. PMID- 8204748 TI - The nerve cell bodies found in the ovine omasal laminae. AB - A histological study was made on the omasum of sheep, cows, sika deer, and Japanese serows in order to confirm the existence of the submucosal nerve cell bodies in the omasal laminae. In the present study, seventeen submucosal nerve cell bodies were found in seven sections from four out of twenty-two sheep. PMID- 8204749 TI - Scintigraphic and ultrasonographic diagnosis of soft tissue injury in a thoroughbred horse. AB - A 2.5-year-old female Thoroughbred horse was referred to the veterinary teaching hospital for right front limb lameness of 1 year duration. Physical examination and diagnostic nerve blocks failed to localize the origin of the lameness. Scintigraphy with 99mTc-MDP suggested increased radionuclide uptake in the palmar metacarpal soft tissues of the right front limb. Ultrasonographic examination revealed hypoechoic lesions in the superficial digital flexor tendon and the suspensory ligament, suggesting tendinitis and desmitis. Combined imaging modalities improved detection and characterization of the cause of a long standing obscure lameness. PMID- 8204750 TI - Nuclear and cytoplasmic maturation of pig oocytes cultured in the amniotic fluid of developing chick embryos. AB - Studies were conducted to determine if the amniotic fluid of a developing chick embryo (CEAm) could be used as a co-culture system for the maturation of pig oocytes. In Exp. 1, the pig oocytes were cultured in mTCM-199 (control) or day 3, 4 and 5 CEAm. The maturation rate of pig oocytes in the control vs CEAm was significantly higher (P < 0.001). The maturation rate of pig oocytes cultured in day 3 vs day 4 and 5 CEAm was significantly higher (P < 0.001). In Exp. 2, the pig oocytes were cultured in day 3 CEAm maintained either in a conventional incubator with 40-70% relative humidity or incubator with 5% CO2 in air atmosphere at 37 degrees C or 39 degrees C. A significantly lower maturation rate (P < 0.001) was obtained when CEAm were maintained in an incubator with 5% CO2 gas atmosphere regardless of the temperature. In Exp. 3, pig oocytes cultured in day 3 CEAm and mTCM-199 (control) were fertilized in vitro (IVF). The penetration and male pronucleus (MPN) formation of pig oocytes cultured in day 3 CEAm was significantly lower (P < 0.01) than those cultured in mTCM-199 medium. The results presented here demonstrate that CEAm could be used to induce maturation of pigs oocytes, however its efficacy is influenced by factors such as developmental stages of chick embryos, temperature and gas atmosphere. PMID- 8204751 TI - Human c-yes-1-related proto-oncogene in clinically normal dogs. AB - Human c-yes-1-related canine proto-oncogene in genomic DNAs from 21 clinically normal dogs was analyzed by Southern blot hybridization. The present study indicated that this proto-oncogene was well conserved in clinically normal dogs, however, there were structural changes in some dogs. These changes were different in each individuals and detected in low frequency. PMID- 8204752 TI - Water consumption in suckling pigs. AB - Water consumption was measured in 199 suckling pigs aged 1 to 28 days. The suckling pigs began to drink water 3 to 5 hr after birth. Water consumption per pig increased from 36 ml/day at the age of 1 day to 403 ml/day at the age of 28 days. Water consumption per kg body weight, on the other hand, remained constant at 51 to 62 ml, regardless of age. This results indicates that it may be possible to add drugs to drinking water for the purpose of medication in suckling pigs. PMID- 8204753 TI - Local pathological reactions induced in pigs and cats by adjuvant ISA-70 containing inactivated Newcastle disease virus antigen. AB - Gross and microscopic changes at the injection site in pigs and cats were investigated for 8 weeks after an intramuscular injection of oil adjuvant ISA-70 emulsion, containing inactivated Newcastle disease virus antigen. In pigs, an egg sized and discolored lesion with pinpoint to miliary-sized nodules was observed at 2 to 8 weeks post injection (PI). In cats, there was partial thickening of the subcutaneous tissue at 2 to 8 weeks PI. Histopathologic changes in pigs were fundamentally similar to those in cats, however, the local tissue reactions in pigs were severer and more protracted than those in cats. The lesions in pigs were characterized by formation of large-sized cysts and well-developed encapsulation of the cysts with epithelioid cells. PMID- 8204754 TI - Detection of the antibodies against porcine cytomegalovirus from whole blood collected on the blood sampling paper. AB - The usefulness of blood sampling paper for the detection of antibodies against porcine cytomegalovirus (PCMV) by enzyme-linked immunosorbent assay (ELISA) was examined. The PCMV antibody titer of whole blood collected on the paper agreed with that of serum and the absorbances of the corresponding samples were well correlated (r = 0.88). Blood was collected from 26 piglets in the field on the blood sampling paper and ELISA was performed. The maternal PCMV antibody of these piglets decreased during the 8 weeks after birth and IgM antibody against PCMV was detected in four piglets. PMID- 8204755 TI - The first case of equine motor neuron disease in Japan. AB - A 9-year-old male horse showed emaciation, weakness and trembling and was euthanatized. Histopathological examinations revealed loss, swelling and chromatolysis of motor neurons throughout the spinal ventral horns, axonal degeneration of the ventral spinal roots. Eosinophilic cytoplasmic inclusions were distributed in degenerated spinal ventral neurons. Ultrastructurally, the inclusions consisted of aggregations of granular dense material and a few vesicles. They reacted positively with polyclonal antibody against ubiquitin. The present case was diagnosed as equine motor neuron disease, which has recently been reported in North America and the United Kingdom. PMID- 8204756 TI - Comparison of the Rev transactivation of feline immunodeficiency virus in feline and non-feline cell lines. AB - The Rev protein of feline immunodeficiency virus (FIV) differentially transactivates the expression of viral structural proteins by allowing the accumulation of unspliced and singly spliced viral mRNA in cytoplasm via the Rev response element (RRE) at the end of env. To investigate the role of rev gene of FIV for the virus life cycle and cell tropism, we constructed the Rev expression plasmids, and functional activity of the Rev was assayed by using chloramphenicol acetyltransferase (CAT) assay system in feline and non-feline cell lines. Although the FIV Rev protein showed high transactivity to result in enhanced CAT production in a feline cell line, the productions of the CAT in non-feline cell lines were significantly lower than that in the feline cell line. These results indicate that specific cellular factor(s) present in feline cell line is required for the FIV Rev full-action and also suggest that the Rev action plays one of the important roles in determining the FIV cell tropism. PMID- 8204757 TI - Two cases of parafilariasis in dairy cattle and treatment of hemorrhage with levamisole topical application. AB - On June and August in 1989, cutaneous hemorrhagic parafilariasis was found in two cattle among 30 pregnant dairy cattle transported from Hokkaido to Chiba Prefecture. One adult female worm each was recovered from the blood spot in both cattle. Ivermectin oral administration, dosage rate of 200 micrograms/kg body weight, had no effect on the occurrence of the blood spots. Topical application of levamisole on a blood spot at a 2.5% concentration showed to stop the bleeding within a few minutes after treatment. This method was very easy to use at the farm situation where cutaneous hemorrhagic parafilariasis sporadically occurred. The disease has not been found in Chiba Prefecture on a whole since those cases in 1989. PMID- 8204758 TI - Development of Babesia ovata in the salivary glands of the nymphal tick, Haemaphysalis longicornis. AB - The development of Babesia ovata in the salivary glands of nymphal Haemaphysalis longicornis ticks was morphologically studied for 4 days of feeding of tick on rabbits. Babesia ovata showed two forms (sporont and sporozoite) in the budding process. Sporozoites were formed in the acinar cells of salivary glands and released from the hollow cytoplasmic area of these cells by day 4 of feeding. PMID- 8204759 TI - An ultrastructural study of the Sertoli cell in the Shiba goat. AB - The ultrastructure of the Shiba goat Sertoli cell was observed using light and transmission electron microscopy. In the basal portion of the Sertoli cell, the nucleus was located near the basement membrane and was irregular in outline. A number of filaments with intermediate width were observed around the nucleus. A multivesicular nuclear body, composed of numerous vesicles of different sizes and ribosome-like structures, was detected within the nucleus. The majority of cell organelles was situated in this basal portion of the cytoplasm. Oval mitochondria were randomly distributed. A well-developed laminated smooth endoplasmic reticulum (sER) was frequently found within the cytoplasm of Sertoli cell. Lysosomes and large lipid droplets were also recognized. While, the outline of the basal lamina was almost straight. No nodular processes were observed in the lamina. The Golgi complex appeared only in the supranuclear region. In the middle and apical portions of the Sertoli cell, elongated mitochondria and microtubules were oriented parallel to the long axis of the cell. The laminated sER was also detected in these portions. The apical head of slightly-elongated spermatids was occasionally surrounded by the laminated sER. The head of maturing spermatids without laminated sER revealed a bleb-like shape. The microfilament bundles at the ectoplasmic specialization site were regularly arranged. Judging from the present observations, we have suggested that only the multivesicular nuclear body and the laminated sER may be the peculiar structures which are commonly found in the Sertoli cell of ruminants. PMID- 8204760 TI - Cardiovascular effects of intermittent positive pressure ventilation in the anesthetized horse. AB - Intermittent positive pressure ventilation (IPPV) is useful method for compensate of respiratory function in anesthetized horses. However, IPPV may decrease cardiac output. Alterations in cardiac output of three groups (N = 5) healthy, halothane-anesthetized mares were determined and compared during a 120 min period of anesthesia. The groups were as follows: spontaneous ventilation (SV), controlled ventilation using an end-inspiratory pressure of 20 cmH2O (CV20) and a third group using 25 cmH2O (CV25) inspiratory pressure. In the CV groups, respiratory function was adequately maintained. Although, cardiac output tended to decrease over time in each group. After 105 min of anesthesia in the CV groups, the cardiac outputs decreased below 50 percent of pre-anesthetic values. In the CV25 group, cardiac outputs were significant difference (p < 0.05) from the SV group after 45, 90 and 120 min of anesthesia. There was no significant difference in cardiac output between SV and CV20 group over time. These values suggest that when long durations of anesthesia was used with the IPPV, decrease of cardiac output should be improved. In clinical use of halothane anesthesia, an end-respiratory pressure of 20 cmH2O seems to be appropriate because the mild decrease in cardiac output was observed even though a little high PaCO2. PMID- 8204761 TI - Delayed-type hypersensitivity in mice experimentally infected with Fusobacterium necrophorum. AB - The foot-pad test was performed to reveal the induction of delayed-type hypersensitivity (DTH) to Fusobacterium necrophorum in mice experimentally infected with F. necrophorum. For the foot-pad test, heat-killed cells of F. necrophorum were found to be better than viable bacteria as eliciting antigens. The thickness of foot-pad could be measured properly at 48 hr after administration to the foot-pad of heat-killed bacteria. An intraperitoneal dose of the order of 10(5) or 10(6) of viable bacteria evoked a similar foot-pad response. Peak responses were found on days 4 and 14 after the sensitization. The response was found to be specific. This response could be transferred by spleen cells to genetically homogeneous mice, but not to genetically heterogeneous mice. Serum could not transfer the response to either heterogeneous or homogeneous mice. Thus, these results indicate that DTH could be induced by F. necrophorum. PMID- 8204762 TI - Permeability of mammary gland capillaries to ferritin in mice. AB - The permeability of mammary gland capillaries to ferritin was investigated by transmission electron microscopy. In virgin mice, the concentration of tracers in perivascular spaces increased with the advance of time after injection. The ferritin never passed through the intercellular junction of the endothelial cells. In the early to middle stages of lactation, numerous ferritin particles were observed in the basal cytoplasm of alveolar epithelial cells after only 1 min of circulation. These findings indicate that a large amount of materials quickly pass through the capillary walls during these periods for milk production. The number of vesicles labelled with ferritin per micron2 of endothelial cytoplasm decreased remarkably in the late stage of lactation. This result suggests that the permeability of vesicles declines along with the degeneration of alveolar cells. PMID- 8204763 TI - A new immunohistochemical method for quantification of fast-myosin in frozen histologic sections of the rat skeletal muscles. AB - An immunohistochemical micromethod for quantification of fast-myosin in frozen histologic sections of rat skeletal muscles was developed. The principle of this method was enzyme-linked immunosorbent assay (ELISA). We used frozen tissue sections as models of the antigen-coated wells of ELISA plate. The intensity of immunoreactivity of the frozen section to an anti-fast-myosin monoclonal antibody was quantified directly from the color developed with the second antibody coupled with peroxidase using phenol-4-aminoantipyrine as a substrate. Then, the same section was incubated in 0.01 M acetic acid solution to cleave antigen-antibody complexes, followed by colorimetric measurement to obtain the absolute value of total protein per section. Fast-myosin content in the frozen tissue section was expressed as mg of fast-myosin per g of total protein. In this micromethod, the minimum area and the optimum thickness of the section were 5 mm2 and 10 microns, respectively. Fast-myosin contents in the extensor digitorum longus and soleus muscles were 185.0 +/- 6.1 and 17.5 +/- 2.4 mg/g, respectively. The results obtained by this micromethod were in good agreement with those obtained by two conventional methods, immunohistochemical morphometry and biochemical determination. This micromethod is useful for a quantitative evaluation of the contractile function of the mammalian skeletal muscles. PMID- 8204764 TI - Analysis of longitudinal distribution of pulmonary vascular resistance by use of a five element lumped model. AB - To analyze longitudinal distribution of pulmonary vascular resistance, we proposed a five element lumped model which partitioned pulmonary circulation into pulmonary arterial, middle and pulmonary venous segment. The validity and anatomical correlation of the model were tested in an isolated, perfused, canine lung lobe preparation with inflow/outflow occlusion techniques. With arterial occlusion, pulmonary arterial pressure fell rapidly and then exponentially. With venous occlusion, pulmonary venous pressure rose suddenly and then exponentially. Theoretical pressure profiles produced by computer simulation of the model well approximated the general characteristics of the experimental traces. Serotonin increased the pressure gradient across the pulmonary arterial segment (delta Pa), whereas histamine increased the gradient across the pulmonary venous segment (delta Pv). Neither drug altered the gradient across the middle segment (delta Pm). The results suggest that the lumped model is a useful concept to understand the longitudinal distribution of pulmonary vascular resistance, and that delta Pa, delta Pm and delta Pv reflect the resistance distribution of anatomical pulmonary arteries, alveolar vessels and pulmonary veins, respectively. PMID- 8204765 TI - Pathogenicity of Mycobacterium avium Serovar 1 isolated from swine in Japan for the first time. AB - A total of 116 strains of Mycobacterium avium-intracellulare complex were isolated from swine with tuberculous lesions at meat inspection, during 1982 1983. Of them, one strain isolated from the lesion in the mesenteric lymph nodes was identified as M. avium serovar 1 (swine strain). The pathogenicity of the swine strain in chickens was compared with that of a reference strain (M. avium serovar 1). Chickens were inoculated intravenously with each strain (2 x 10(6) colony forming units: CFU) and they were autopsied at 30 days after inoculation. Enlargement of the liver, spleen and kidney was observed in the inoculated chickens. In histopathological examination, many granulomatous lesions were observed in the lung, liver and spleen. Infiltration of lymphocytes was found in the kidney and pancreas. Both inoculated organisms were recovered from the liver (10(3)-10(6) CFU/g) and spleen (10(3)-10(5) CFU/g) of each inoculated chicken. The reference strain (< 3.0 x 10(2) CFU/g, ml) was also recovered from the lung, kidney, pancreas and the bile of the inoculated chickens. All the isolates were identified as serovar 1. It was shown that the swine strain had pathogenicity in chickens comparable to that of the reference strain. PMID- 8204766 TI - Comparison of atherogenicity of soybean oil and peanut oil, and effect of clentiazem on diet-induced atherosclerosis in rabbits. AB - Rabbits were fed with two kinds of atherogenic diet, one containing 0.5% cholesterol and 3% soybean oil and the other 0.5% cholesterol and 6% peanut oil, for three months to compare the atherogenic property of the diets. The soybean oil diet seemed to be superior to the peanut oil diet for evaluation of the anti atherogenic effect of drugs, because the former caused milder vascular lesions than the latter. Using this rabbit model for atherosclerosis, the anti atherogenic effect of clentiazem, a new calcium antagonist, was examined. Clentiazem at an oral dose of 30 mg/kg/day significantly reduced the size of atheromatous lesion in the aortic arch and thoracic aorta, and lowered the collagen content of the aortic intima and media, although it did not decrease serum lipid levels. On the other hand, clentiazem showed no clear effect on reducing the coronary atherosclerotic lesions. These results suggest that clentiazem may inhibit the progression of diet-induced aortic atherosclerosis without normalizing the serum lipid levels. PMID- 8204767 TI - Effects of ionic and nonionic contrast media on cardiohemodynamics and quality of radiographic image during canine angiography. AB - Cardiovascular responses and radiographic image quality during cerebral angiography, aortofemoral angiography and left ventriculography with nonionic ioxilan, iohexol or iopamidol were compared with those of ionic sodium meglumine diatrizoate in pentobarbital anesthetized dogs. Injection of all contrast media caused cardiovascular changes to a greater or lesser degree, e.g., hypotension, bradycardia, tachycardia, a decrease in left ventricular pressure (LVP) and its first derivative (dP/dt), and prolongation of the P-Q and Q-T intervals. Ionic diatrizoate had a greater effect on cardiovascular parameters than nonionic contrast media during angiography in all areas. Moreover, diatrizoate produced cardiac arrhythmias and prominent changes in blood rheology concerned with blood viscosity and deformability of the erythrocyte. The cause of various effects of contrast media seemed to lie mainly in osmolality, viscosity and partially ionic additives. The radiographic image quality of all of the contrast media used was similar, but nonionic ioxilan and iohexol with lower iodine content and low osmolality gave better radio opacity than ionic diatrizoate in cerebral angiography. These results suggested that nonionic contrast media should be recommended as a diagnostic tool for both animals and human patients in poor health. PMID- 8204768 TI - Effect of passive immunization with serotype-specific monoclonal antibodies on Actinobacillus pleuropneumoniae infection of mice. AB - Specific monoclonal antibodies (MoAbs) to Actinobacillus pleuropneumoniae (APP) serotypes 1 and 2 which recognized serotype-specific antigens were produced. It was revealed that the two serotype-specific MoAbs H1-18 and H22-7 recognized O polysaccharides of the lipopolysaccharide (LPS) from APP serotypes 1 and 2, respectively, in the results of antigen analysis by means of SDS-PAGE and Western blotting. Furthermore, ddY mice immunized passively with the above type-specific MoAbs were protected against challenge infection by the homologous serotype of APP at 24 or 48 hr later. However, H1-9 and H3-2 MoAbs recognizing serotype common protein antigens of APP did not show signs of any protective effect. These results showed that LPS from APP bacterial cells was one of the structural substances in the serotype-specific antigens, and an important component as one of the antigens protecting against the homologous serotype strain. PMID- 8204769 TI - Histological methods for assessing myelin sheaths and axons in human nerve trunks. AB - Although there are many histological techniques for assessing myelin sheaths and axons in paraffin embedded or frozen sections of the peripheral nervous system, modern approaches usually use plastic embedded material. Although plastic embedding is superior for small cutaneous branches, this method has limited value for histological assessment of nerve trunks. We report three methods which together yield a comprehensive approach for thorough and detailed investigation of human nerve trunks. The rapid osmication method permitted assessment of myelinated nerve fibers from frozen sections at operation, thus providing the surgeon with guidance on the extent of nerve resection. The modification presented here resulted in permanent slides, allowing comparison of results with those of the other two procedures. The new osmium-hematoxylin technique could be performed on paraffin embedded nerves. Paraffin, unlike plastic, permitted the study of the whole cross sectional area of the nerve in single sections. Moreover, the sharp image of the myelin permitted computerized morphometry. The significantly modified axonal silver impregnation technique was performed on frozen sections mounted on glass slides, as opposed to the time-consuming impregnation of free-floating sections. The latter technique had a high success rate and permitted semiquantitative assessment of axons in nerve trunks. These methods can be performed in any routine histology laboratory and resulted in greater accuracy compared to conventional methods. PMID- 8204770 TI - Device to prepare extruded nuclei and chromosome squashes. AB - A horizontal toggle clamp mounted on a rigid base plate makes nuclear extrusion and polytene chromosome squashing simple and reproducible. The base plate has a stage with shallow flat grooves to align the tissue sample directly below the clamp's swivel foot and hold the microscope slide in place during squashing. Appropriate pressure to obtain either extruded nuclei or squash preparations of polytene chromosomes is established empirically by adjusting the clamp's spindle assembly up or down. PMID- 8204771 TI - Cryofixation combined with physical dehydration for quantitative immunoelectron cytochemistry. AB - Common methods for preparing samples for immunoelectron microscopy involve glutaraldehyde fixation (GA) followed by chemical dehydration (CD) or cryofixation (CF) succeeded by physical dehydration, i.e., freeze drying (FD) or freeze substitution (FS). The effects of these techniques have been evaluated with regard to the sizes of epoxy resin embedded rat somatotrophic secretory granules as well as the immunolabeling densities over these granules. The measurements were performed by computerized image analysis using electron microscopy in transmission (TEM) and scanning transmission (STEM) modes, which allowed us to define the immunolabeling in detail. The embedded secretory granules showed the same diameters after GA (2 hr) with CD and GA (15 min) with CF and FS, but were smaller after CF-FS, and smallest after GA (15 min) with CF and FD. The highest labeling density appeared after GA (15 min) and physical dehydration, in particular after freeze substitution. Based on our STEM pictures a new factor for evaluating and interpreting immunolabeling of granules is introduced; the "accessible immunogold labeling surface." It defines the fraction of the epoxy resin surface that is labeled and varies with the preparation methods. By using this factor, an order of labeling densities/micron 2 over the accessible areas could be established for the different techniques: GA-CF-FS > CF FS > GA-CF-FD > GA-CD. The high labeling after GA-CF-FS may be due to the combination of a large accessible area and accurate preservation of the antigenicity of the hormones in the granules. PMID- 8204772 TI - An improved method for rapid fixation and embedding of pteridophyte plant materials. AB - A rapid method for fixation and embedding of plant materials, especially pteridophytes, is suggested. Addition of tannic acid following osmication improved the visualization of membranes. Staining en bloc with uranyl acetate between osmication and tannic acid is suggested for tissues infected with fungi and bacteria. PMID- 8204773 TI - Disease due to the Mycobacterium avium complex in patients with AIDS: epidemiology and clinical syndrome. AB - Infection due to the Mycobacterium avium complex (MAC) is the most common opportunistic disease of bacterial origin among patients with AIDS in the United States. The incidence of disseminated disease due to MAC (DMAC) has risen dramatically in recent years. The risk of developing DMAC increases as the CD4+ lymphocyte count declines to < 100/mm3. Preliminary analyses of several studies suggest that gender, racial or ethnic group, and individual risk factors for human immunodeficiency virus infection do not influence the incidence of DMAC but that prior Pneumocystis carinii pneumonia, the development of severe anemia, or the interruption of antiretroviral therapy may increase risk. Both the respiratory and the gastrointestinal tracts probably serve as portals of entry for MAC. Colonization may potentiate the risk of DMAC but does not always precede dissemination. Patients with AIDS and DMAC have a shorter duration of survival than do those with AIDS but without DMAC. While treatment for DMAC may extend survival, no well-controlled, prospective, randomized clinical trial has documented this point. Most patients with AIDS and DMAC have disseminated multiorgan disease; the most frequently described symptoms include fever, night sweats, weight loss or wasting, diarrhea, and abdominal pain. The most commonly identified laboratory abnormalities are anemia and elevated serum levels of alkaline phosphatase. Localized disease syndromes related to MAC infection occur less often. PMID- 8204774 TI - Prophylaxis of Mycobacterium avium complex bacteremia in patients with AIDS. AB - Prevention of opportunistic infections is an integral part of caring for patients infected with human immunodeficiency virus. Mycobacterium avium complex (MAC) bacteremia can cause severe morbidity and excess mortality among these patients. Controlled trials of rifabutin for the prophylaxis of MAC bacteremia have been completed. Rifabutin reduced the incidence of MAC bacteremia by approximately one half and, when disseminated disease due to MAC (DMAC) did develop, reduced the frequency of associated clinical symptoms. Moreover, prophylaxis with rifabutin was well tolerated. Prophylaxis of MAC bacteremia with macrolide antibiotics is currently being investigated, but no data from large-scale prospective trials are yet available. On the basis of trials completed thus far, the U.S. Public Health Service has recently recommended the use of rifabutin (300 mg/d) as prophylaxis for MAC bacteremia in patients with fewer than 100 CD4+ lymphocytes/mm3. The widespread use of this prophylactic regimen could reduce the rates of morbidity and mortality caused by DMAC. However, rifabutin must be administered only after careful consideration of the circumstances of individual patients. Potential drug interactions, cost, and compliance are important factors in the decision about which patients should receive prophylaxis. PMID- 8204775 TI - Assessment of new therapies for infection due to the Mycobacterium avium complex: appropriate use of in vitro and in vivo testing. AB - Laboratory testing is a prerequisite to predictions about the potential value of human clinical trials--the gold standard for the assessment of new therapies for infection with the Mycobacterium avium complex (MAC). These laboratory assessments must be made in the proper sequence, with appropriate models and methodology used to obtain data valid in determining whether clinical trials are warranted. In vitro testing permits measurements of minimal inhibitory and minimal bactericidal concentrations, identification of the synergism or antagonism of various agents, definition of an agent's pharmacokinetic properties (e.g., hydrophilicity or lipophilicity), and evaluation of a drug's intracellular penetration and activity against intracellular organisms. The most appropriate animal model for in vivo testing of activity against MAC is the beige mouse. Experiments in this model provide important data on an agent's minimal effective dose and on its optimal dose, dosing frequency, and route(s) of administration. Evaluations in the beige mouse also document whether the agent is bactericidal or bacteriostatic, whether it selects drug-resistant mutants, and whether its use in combination with other agents is beneficial. PMID- 8204776 TI - Treatment of disseminated disease due to the Mycobacterium avium complex in patients with AIDS. AB - Perhaps the most important recent advance in the field of infections due to the Mycobacterium avium complex (MAC) is the identification and development of more effective agents for the treatment and prevention of disseminated disease. These agents include clarithromycin, azithromycin, rifabutin and other rifamycins, ethambutol, clofazimine, fluoroquinolones, amikacin, and liposome-encapsulated gentamicin. Most clinicians currently use multidrug therapy to maximize efficacy and to minimize the emergence of resistance. Prospective clinical trials of multidrug regimens suggest that MAC colony counts in blood decline during therapy, usually with alleviation of clinical symptoms. The small size and short duration of these trials have not permitted an evaluation of survival or quality of life. Because the contribution of any single agent to multidrug trials is difficult to assess, short-term trials of monotherapy have been conducted recently; clarithromycin, azithromycin, ethambutol, and liposome-encapsulated gentamicin have been most active. Rifabutin and rifampin, clofazimine, amikacin, and ciprofloxacin may contribute to the efficacy of multidrug regimens. Current recommendations include the following: (1) disseminated MAC disease should be treated in patients with AIDS; (2) initial treatment should consist of at least two agents; (3) oral clarithromycin or azithromycin is the preferred first agent; (4) ethambutol is the most rational choice for the second agent; and (5) in appropriate cases, additional agents (rifampin or rifabutin, clofazimine, ciprofloxacin, or parenteral amikacin) may be added. Therapy should continue for life. PMID- 8204777 TI - [The reform of primary care in Spain. Perspectives of a decade of family medicine]. PMID- 8204778 TI - [Private management of primary care services]. PMID- 8204779 TI - [Morbidity among African immigrant population attended at a health center]. AB - OBJECTIVE: To deepen the demographic study of the immigrant population from West Africa who regularly sought health-care at our Health Centre and to analyse their morbidity. DESIGN: A retrospective observation study of a crossover type. SETTING: Salt Basic Health Area, in the Girona Health Region. PATIENTS: The black population originating in West Africa and resident in Salt, whose clinical notes were in the Centre's records. RESULTS: The 57 people registered attended 436 times, of which 289 were for the Paediatric Clinics. Of these 289, 40% were handled by the paediatric nurses. The average frequency of visit by age ranged from 2 attendances a year (20-29 years old) to 14 per year (under 14 years old). In 25.95% of the consultations involving paediatric teams and in 19.05% of those involving adults, no medical diagnosis was made. The most common paediatric diagnoses were, following the CIPSAP-2-WONCA classification: Supplementary Classification (25.95%) and Pathology of the Respiratory System (20.07%). Among adults, Pathologies of the Digestive System (21.77%) and Infectious and Parasite Diseases (12.93%) were the two most common illnesses. Additional tests to assist diagnosis or a simple preventive screening were rarely requested. CONCLUSIONS: Tackling the problems of the black-african population at the Primary Care level is limited by lack of knowledge of tropical diseases, the scant specific bibliography available, linguistic and cultural barriers and the lack of institutional delivery of health-care to the clandestine population. Alternatives are proposed, such as: an operating procedure, and interdisciplinary socio sanitary programme. PMID- 8204780 TI - [Domiciliary care of the terminal cancer patient: evaluation and proposals by physicians and nurses]. AB - OBJECTIVE: To detect problems that terminal cancer patients pose to primary health care (PHC) professionals. DESIGN: Cross-sectional study. SETTING: PHC professionals of the Manresa (province of Barcelona) health Sector of the National Health System. PARTICIPANTS: 151 professionals (87 physicians and 64 nurses). MEASUREMENTS AND RESULTS: Self-responded anonymous questionnaire. Dates: 10-20 December, 1990; response rate: 89%. Most participants said in the previous year they were responsible for 3 or more home terminal cancer patients. 35.6% said emergencies were handled in a hospital; professionals working in non-urban areas and in the non-reformed Primary Care system less often used hospitals. Access to consultants was deemed difficult by most interviewees, but most said consultants' reports were good or excellent; physicians valued reports higher than nurses (odds ratio [OR] = 5.43, P < 0.001). Most participants reported continuous education to be scarce or nonexistent. Also, most said care given to terminal cancer patients was inadequate; younger professionals (p = 0.001) y and those working in the reformed Primary Care system (P = 0.003) were more critical. CONCLUSIONS: Interest of primary care professionals in terminal cancer patients was higher in less populated areas, among those having a permanent contract and in the reformed system. PMID- 8204781 TI - [Use of serological markers of hepatitis B and C viruses in a health center]. AB - OBJECTIVE: To find the use of serological markers for the Hepatitis B (HBV) and Hepatitis C (HCV) viruses by doctors at an urban Health Centre, assessing the number of requests and their diagnostic effectiveness. DESIGN: Prospective and retrospective study of observation. SETTING: Primary Care. Urban Health Centre. PATIENTS: All those for whom requests for HBV and HCV serological markers were made between 1.1.92 and 30.3.93. MEASUREMENTS AND MAIN RESULTS: A total of 131 requests for HBV markers and 82 for HVC ones were made during the study period (1% of the total analyses performed). 30.5% of the HBV markers and 12.2% of the HCV ones were positive. 36% of the requests for HBV markers were for preventive as against 64% for diagnostic reasons. The diagnostic effectiveness (percentage of positives among the requests made for diagnostic reasons) was 35.7% for HBV and 13% for HCV serology. The manner of contagion could not be determined from the information collected in the clinical notes for 56% of the patients with positive serology. The performance of a Hepatic Biopsy was recorded for 10% of the patients with positive HBV or HCV serology, with diagnoses of 4 cases of active chronic Hepatitis and one of late cutaneous Porphyria. CONCLUSIONS: The availability of an accessible and correct request form for HBV and HCV markers could assist greater diagnostic accuracy and referral to specialists if required. PMID- 8204782 TI - [Adverse reactions to drugs reported by the primary care physicians of Andalusia. Analysis of underreporting]. AB - OBJECTIVE: To discover the sort of adverse reactions to medication (ARM) notified by Primary Care doctors and identify the under-notification of those cases having special clinical-epidemiological interest. DESIGN: Retrospective study in which 2,597 ARM corresponding to 1,467 Yellow Cards (YC) were analysed. These were notified by Primary Care doctors to the Centro Andaluz de Farmacovigilancia (Andalusian Drug-watch centre) during the period from 1/6/90 to 31/12/92. To assess the seriousness of the ARM, their terminological classification and imputability, the criteria used in the WHO's international "Yellow Card" programme of spontaneous notification were followed. MEASUREMENTS AND MAIN RESULTS: 77.2% of all notifications were from Primary Care, of which 7.4% were of special interest due to their serious or novel character. However an undernotification of serious and well-known ARM was detected, such as digestive haemorrhages (1.07/10(6) inhibitants per year), anaphylactic shock (0.34/10(6) inhab/year), agranulocytosis (0.23/10(6) inhab/year) and aplastic anaemia (0.05/10(6) inhab/year), among others. CONCLUSIONS: Most of the main under notified ARM are generated in the community but treated in hospital Casualty departments. Therefore it would be useful to develop specific Drug-watch programmes in the hospitals themselves. PMID- 8204783 TI - [Self medication in general pediatrics]. AB - OBJECTIVE: Description and quantification of self medication in a general paediatric office. DESIGN: Descriptive and prospective study. SITE. Cervantes Health Centre (Guadalajara). PATIENTS: 387 cases of both sexes until 8 that attended to on demand consultation during the period of two months. MEASUREMENTS AND MAIN RESULTS: 36% of the patients were given drugs before attending to consultation and in 18.7% of these cases, the actuation was incorrect. Parents were, mainly the responsible of incorrect treatment. The most often registered pathology was common cold. We did not found relation between self medication and the next variables: child's age or sex, parents' age or studies, number of children in the family, number of consultation for the same pathologic event and mother working outside home. CONCLUSIONS: Self medication is a common practice. Parents should be instructed about management of the commonest pathologies and when they should ask the doctor. PMID- 8204784 TI - [Epidemiological study of primary brain tumors in the Autonomous Community of Aragon]. AB - OBJECTIVES: a) To analyse diverse clinical features related to the symptomatology, location and anatomopathological diagnosis of primary tumours of the C.N.S. and b) to improve knowledge of the frequency of cerebral tumours in our field of study. DESIGN: A protocolized and retrospective study of those patients diagnosed as having a primary cerebral Neoplasia. SETTING: The Autonomous Community of Aragon during the decade from 1980 to 1990. PATIENTS AND OTHER PARTICIPANTS: Our total sample consisted of 759 tumours, 412 (54.28%) in men and 347 (45.72%) in women. Our criterion for inclusion was a diagnosis of primary cerebral Neoplasia, excluding Metastasis and vascular tumours. MEASUREMENTS AND MAIN RESULTS: The majority of the cerebral tumours were located in the cerebral hemispheres (56%): migraine was the most common symptom. We confirmed that the occurrence of cerebral tumours was higher in urban than in rural zones. However the age at which these neoplastic intracranial processes present is greater in rural zones. For 67% of patients 4.5 months had to pass before it was possible to establish the diagnosis of expansive intracranial process. CONCLUSIONS: a) Migraine is the most common clinical manifestation (20%), followed by a disturbance of the higher functions (15%). b) There is considerable delay in the time needed to establish the diagnosis of expansive intracranial process, due to the present health-care framework. c) The occurrence of cerebral tumours is higher in urban than in rural zones. PMID- 8204785 TI - [Implementation of a hypertension protocol in a basic health area as a basis for a medical audit]. AB - OBJECTIVE: To analyse compliance in the application of the Arterial Hypertension procedure and the level of monitoring of our hypertensive patients. To introduce quality control methodology into the Primary Care team's work systems. DESIGN: Observation study of a crossover type. SETTING: Primary Care. Plaza Cataluna PCC, Manresa (Barcelona). PATIENTS: Audit of 100 medical records of hypertensive patients selected by systematic random sampling from a total of 533 hypertensive patients under 70 years old. MEASUREMENTS AND MAIN RESULTS: 43% of the hypertensive patients had their pressure figures adequately monitored (CI 95%: 33.3-52.7) with 4.86 average number of checks per year. Analytic blood controls were performed on 66% and urine controls on 56%. Only 34% of patients had a minimal cardiovascular investigation, while back-of-eye investigation and ECGs were performed on 44% and 49%, respectively. CONCLUSIONS: The arterial pressure monitoring level is acceptable. Compliance with the procedure is deficient in most complementary investigations. The periodicity of ECGs should be agreed. It is clear that patients for whom compliance with the procedure is most deficient are those who have fewer arterial pressure recordings as well as those receiving no drugs treatment. New objectives are proposed. Lastly, corrective measures are suggested, with a reassessment after two years. PMID- 8204786 TI - [Colorectal cancer. A current perspective from the primary care viewpoint]. PMID- 8204787 TI - [Sexual dysfunction due to captopril and amlodipine]. PMID- 8204788 TI - [Aceclofenac and mental confusion]. PMID- 8204789 TI - ["R" syndrome]. PMID- 8204790 TI - [Outbreak of acute cholestatic hepatitis A in a family. An occurrence to be prevented]. PMID- 8204791 TI - [Measles vaccine: importance of the 2d dose]. PMID- 8204792 TI - Effect of thyroid status on basal phosphorylation of cardiac myofibrillar phosphoproteins in rats. AB - The effect of thyroid status on myocardial function and accompanying alterations in the expression of specific genes has been well defined in animals. However, the effects of thyroid hormones on the basal phosphorylation of key cardiac regulatory proteins, which may also contribute to alterations in myocardial function, have not been defined. The present study concerns the phosphorylation status of myofibrillar proteins in hearts from hyperthyroid, euthyroid and hypothyroid rats. Hyperthyroidism was produced by daily subcutaneous injections of L-triiodothyronine, while hypothyroidism was induced with an iodine-deficient diet and KClO4. Two different approaches were used to study changes in the basal phosphorylation levels of troponin I and C protein: 1) direct measurement of the 32P-label associated with these proteins, using intact, beating hearts perfused with [32P]orthophosphate-labeled Krebs buffer; 2) indirect measurement by the back-phosphorylation technique with [gamma-32P]ATP and the catalytic subunit of cAMP-dependent protein kinase in vitro. Measurements of left ventricular contraction (+dP/dt and -dP/dt) were significantly higher in hyperthyroid than in euthyroid animals and this was associated with increases in basal phosphorylation levels of both troponin I and C protein in the myofibrils. In hypothyroid animals, both +dP/dt and -dP/dt were significantly lower than in euthyroid animals and this was associated with decreases in basal phosphorylation levels of troponin I and C protein. The changes in the phosphorylation status of troponin I or C protein correlated with the changes in the speed of myocardial relaxation ( dP/dt) in response to the altered thyroid states.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204793 TI - Role of the heart and peripheral resistance in the reflex effect of group I afferent fibers on blood pressure. AB - Experiments were done on anesthetized and curarized cats to see whether the increase in blood pressure caused by electrical stimulation of group I afferent fibers is related to a direct reflex effect on the heart. The reflex effect of electrical stimulation of group I afferent fibers from the gastrocnemius-soleus muscles on the arterial pressure, the left ventricular pressure, the inotropic state of the left ventricle (dP50/dt) and the heart rate were compared before and after beta-blockade with propranolol (0.1 mg/kg intravenously) to reduce a possible direct effect on the heart. The same comparison was made before and after alpha-blockade with phentolamine (2.5 mg/kg intravenously) to keep the peripheral resistance constant. Electrical stimulation of group I afferent fibers caused an increase in the blood pressure, the left ventricular pressure and, to some extent, the inotropic state of the left ventricle and the heart rate. The beta-blockade had no significant effect on these increases, while the alpha blockade abolished the increase in blood pressure. It is concluded that the effect of stimulation of group I afferent fibers on the blood pressure is not dependent on a direct reflex effect on the heart, but can be better explained by a reflex increase in the peripheral resistance. PMID- 8204794 TI - On the trail of the carotid body. PMID- 8204795 TI - Transverse shape characteristics of cardiac myocytes from rats and humans. AB - The shape of the cardiac myocyte is complex; but, in general, it resembles that of an elliptical cylinder. Quantitative data, however, are lacking and adaptive changes in cross-sectional shape are unknown. The major and minor transverse diameters of myocytes from adult rats were measured using three independent methods: profile tracings of intact isolated myocytes, sectioned isolated myocytes, and whole-sectioned tissue. Values for major and minor diameters were virtually identical with all three methods. Using profile tracings of intact isolated myocytes, major and minor diameters were examined in isolated myocytes from freshly explanted human hearts. Five were non-failing donor hearts regarded as unsuitable for transplantation, of which 2 were normal hearts and 3 had concentric hypertrophy. Six were dilated, failing human hearts with ischemic cardiomyopathy. Major and minor diameters from the normal hearts were similar to those from normal rats. Although the number of patients was limited, the minor diameter was largest in myocytes from patients with concentric hypertrophy while the major diameter was greatest in cells from patients with ischemic cardiomyopathy. We conclude that the cross-sectional shape of structurally-intact myocytes is not altered by cell isolation. The data suggest that the transverse shape of normal human cardiac myocytes is similar to that found in rats, and that it may be altered in hypertrophy and failure. PMID- 8204796 TI - The carotid bodies enlarge in some cases of cirrhosis of the liver. AB - The weights of the individual carotid bodies and cardiac ventricles were obtained at necropsy in five series of subjects. The first comprised 10 cases free of cardiopulmonary disease to act as controls. The second consisted of 10 cases of pulmonary emphysema. The third was composed of 8 cases characterized by sustained alveolar hypoxia due to causes other than pulmonary emphysema. The fourth comprised 10 cases of systemic hypertension or severe left ventricular failure. The fifth was made up of 10 cases of diseases of the liver or alimentary canal. The study confirmed that enlargement of the carotid bodies is common in cases of pulmonary emphysema or sustained alveolar hypoxia with right ventricular hypertrophy. It is also common in cases of systemic hypertension with left ventricular hypertrophy. It was also revealed that enlargement of the carotid bodies may occur in cirrhosis of the liver. We believe this to be the first report of that association. PMID- 8204797 TI - Scanning electron microscopy study of endocardial regeneration in bovine pericardial patch-grafts implanted in the canine heart. AB - The pattern of endocardial regeneration was studied in bovine parietal pericardial patch-grafts implanted in canine hearts. The grafts consisted of fibrous tissue without a cellular lining. They were implanted with either the thoracic or the cardiac surface facing the lumen of the canine ventricle to evaluate the effect on endocardial regeneration. The grafts were retrieved 7, 21, 45 and 60 days after implantation and were examined using scanning electron microscopy. At 7 days, both the thoracic and the cardiac aspect exhibited connective tissue fibers, focally covered by fibrin, platelets and blood cells. The cardiac aspect showed finer and more highly intermingled filamentous fibers than the thoracic aspect. At 21-60 days, the thoracic surface displayed a continuous network of connective fibers with a few blood cells and isolated groups of spindle-shaped cells resembling fibroblasts. At 21-60 days, the cardiac surface showed a diffuse growth of cells on the connective fiber substratum. Regenerating cells first lined the periphery of the grafts (21 days) and then proliferated towards the centrum (45-60 days). These cells varied in size and shape, were mostly closely packed, exhibited numerous microvilli or longer cytoplasmic projections, and resembled regenerating endothelial cells and mature endocardial cells. The topographic arrangement of the new lining cells suggests that they were the result of a per continuitatem regeneration (endothelial re endothelialization) and that they they originated from the healthy endocardium of the host surrounding the implantation site. The arrangement of the connective fibers, finer on the cardiac than on the thoracic aspect, probably facilitated the development of a cellular lining.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204798 TI - Prostacyclin analog (cicaprost) protects against damage by hydrogen peroxide to rabbit cardiac sarcoplasmic reticulum. AB - The membrane fluidity of the cardiac sarcoplasmic reticulum in rabbit was monitored by measuring changes in steady-state fluorescence anisotropy (rs) using diphenylhexatriene as a probe. The Ca(2+)-ATPase activity of the sarcoplasmic reticulum was measured by assaying the amount of inorganic phosphate released from ATP. Hydrogen peroxide caused damage to the sarcoplasmic reticulum, as reflected by decreases in membrane fluidity and Ca(2+)-ATPase activity. The damage caused by hydrogen peroxide was completely prevented by 20 micrograms/ml catalase. Cicaprost (240 nM) provided an effective protection against injury to the sarcoplasmic reticulum caused by exposure to hydrogen peroxide. The rs value was significantly decreased from 0.154 +/- 0.014 to 0.122 +/- 0.005 (p < 0.01). Ca(2+)-ATPase activity was increased from 3.1 +/- 1.31 to 18.87 +/- 2.11 microM phosphate/mg protein/hour (p < 0.01). The protection given by cicaprost was dose dependent. We conclude that cicaprost protects against damage produced by hydrogen peroxide in cardiac sarcoplasmic reticulum in the rabbit. The mechanism of the effect of cicaprost remains to be elucidated. PMID- 8204799 TI - Effects of magnesium orotate on rat heart function. AB - Female Sprague-Dawley rats were given magnesium orotate (100 mg/kg/day) by gavage for 7 days. The effects on left ventricular, right ventricular, and circulatory function were measured using Millar ultraminiature catheter pressure transducers and thermodilution. In another series, rats were pretreated for 4 days with magnesium orotate. Then they received an intravenous infusion of norepinephrine (0.2 mg/kg/h) for 3 days while magnesium orotate treatment was continued. Thereafter, left ventricular function was examined. Magnesium orotate given for 7 days in control rats induced an increase in heart rate from 380 +/- 18 (n = 7) to 415 +/- 9 beats/min (n = 8); in left ventricular systolic pressure from 165 +/- 8 to 183 +/- 10 mmHg; in left ventricular dP/dtmax from 11486 +/- 1082 to 13300 +/- 909 mmHg/s; and in cardiac output from 386 +/- 38 to 429 +/- 16 ml/kg/min. The pressure-rate product was significantly elevated by magnesium orotate from 54956 +/- 4260 to 66094 +/- 3703 mmHg/min (p < 0.05). Right ventricular systolic pressure was also significantly increased from 34 +/- 1 to 41 +/- 3 mmHg (p < 0.05), and right ventricular dP/dtmax was increased from 2233 +/- 167 to 2857 +/- 489 mmHg/s. Infusion of norepinephrine for 3 days induced an increase in heart rate by 34%, in left ventricular systolic pressure by 10%, in left ventricular dP/dtmax by 88%, in right ventricular systolic pressure by 147%, and in right ventricular dP/dtmax by 100%. Magnesium orotate treatment did not significantly affect the changes induced by norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204800 TI - Pronounced antiarrhythmic effects of ischemic preconditioning. AB - Brief periods of ischemia, induced either by complete coronary artery occlusion or by rapid ventricular pacing, greatly reduce the severity of those live threatening ventricular arrhythmias that occur during a subsequent more prolonged occlusion of a major branch of the left coronary artery. The increased tolerance achieved by brief ischemia, either regional or global, has been termed ischemic preconditioning. This was originally defined as the reduction in ultrastructural changes and infarct size resulting from coronary artery occlusion and reperfusion by prior, brief, usually multiple ischemic periods. The reduction in the severity of arrhythmias by preconditioning, which has been described in several different species using both in vivo and in vitro models, depends on the duration and number of the short preconditioning occlusions and also on the time between the preconditioning period and the subsequent prolonged coronary artery occlusion. Under optimal conditions the antiarrhythmic effect of ischemic preconditioning is as pronounced as that with standard antiarrhythmic drugs. Unfortunately, the protection if also short-lived (usually less than 1 hour). If, however, we understood the precise mechanisms involved, we might be able to exploit them to ultimate therapeutic advantage. At least in the dog, the evidence suggests that the protection involves the release (from coronary vascular endothelial cells?) of endogenous myocardial protective substances such as bradykinin, nitric oxide and prostacyclin. PMID- 8204801 TI - Characterization of protein kinase C in rat and human prostates. AB - The properties of protein kinase C (PKC) activity have been studied in cytosolic and membrane fractions from rat and human prostate. Ion exchange chromatography indicated the existence of different PKC isoforms, PKC from rat ventral prostate behaved as a classical Ca(2+)- and phospholipid-dependent enzyme and was activated by 1,2-diacylglycerol as well as by high concentrations of arachidonic acid. PKC activity in the cytosolic fraction was higher and presented different cofactor requirements than that in the membrane fraction. PKC from human benign hyperplastic prostate was also phospholipid dependent, activated by tumor promotong phorbol esters, and appeared to belong to the group of PKC isozymes which lack Ca2+ sensitivity. Human prostatic PKC activity appeared to be of similar nature in both membrane and cytosolic fractions but the specific activity was higher in the particulate preparation which could be related to the stage of endogenous activation of the enzyme. These results extend previous observations in rat ventral prostate and present evidences on the human counterpart. Forthcoming experiments are needed to establish the exact nature of PKC isozymes and their physiological and pathophysiological role in this gland. PMID- 8204802 TI - The effect of clenbuterol on body composition in spontaneously eating tumour bearing mice. AB - The aim of this study was to investigate the effect of a selective beta 2 adrenoceptor agonist, clenbuterol, on body composition in tumour-bearing adult and growing mice. Therefore, adult female C57/BL6 mice (n = 20) were inoculated subcutaneously with a 3-methylcholanthrene-induced sarcoma and divided into two identical groups. One group received injections twice a day of clenbuterol corresponding to 1 mg/kg body weight, the other group received sham injections. Growing mice (n = 20) were similarly divided after tumour inoculation into one study group with clenbuterol injections and one control group. The growing animals were sacrificed on day 11 after commencement of treatment, the adult mice on day 16. Clenbuterol treatment had no statistically significant effect on accumulated food intake or body composition in the adult mice. However, food intake in these animals increased numerically compared to control animals after day 11 of the study. Tumour growth was also unaffected. The growing animals displayed an increased carcass dry weight with borderline significance (p = 0.06) and an increased quadriceps muscle fat free dry weight after clenbuterol treatment. Tumour growth was not affected. Food intake measured on a daily basis was significantly increased in the growing clenbuterol treated animals and accumulated food intake was increased with a trend towards statistical significance (p = 0.06). The results support the suggestion that treatment with a selective beta 2-adrenoceptor agonist does not improve body composition in tumour bearing adult mice relying on spontaneous food intake while growing animals may benefit from such treatment. PMID- 8204803 TI - Semliki Forest virus core protein fragmentation: its possible role in nucleocapsid disassembly. AB - Semliki Forest virus (SFV) envelope proteins function as proton pores under mildly acidic conditions and translocate protons across the viral membrane [Schlegel, A., Omar, A., Jentsch, P., Morell, A. and Kemp, F. C. (1991) Biosci. Rep. 11, 243-255]. As a consequence, during uptake of SFV by cells via receptor mediated endocytosis the nucleocapsid is supposed to be exposed to protons. In this paper the effects of mildly acidic pH on SFV nucleocapsids were examined. A partial proteolytic fragmentation of core proteins was observed when nucleocapsids were exposed to mildly acidic pH. A similar proteolytic event was detected when intact SFV virions were exposed to identical conditions. Protease protection assays with exogenous bromelain provided evidence that the capsid protein degradation was due to an endogenous proteolytic activity and not to a proteolytic contamination. Detergent solubilization of virus particles containing degraded nucleocapsids followed by sucrose gradient centrifugation led to a separation of capsid protein fragments and remaining nucleocapsids. These data are discussed in terms of a putative biological significance, namely that the core protein fragmentation may play a role in nucleocapsid disassembly. PMID- 8204804 TI - Characterization of serine/threonine protein phosphatases in RINm5F insulinoma cells. AB - This study investigates the occurrence and regulation of serine/threonine protein phosphatases (PPases) in insulin-secreting RINm5F insulinoma cells. PPases types 1 and 2A were identified in crude RINm5F cell homogenates by both enzymatic assay and Western blot analysis. We then characterized and compared the inhibitory actions of several compounds isolated from cyanobacteria, marine dinoflagellates and marine sponges, (viz. okadaic acid, microcystin-LR, calyculin-A and nodularin) cation-independent PPase activities in RINm5F cell homogenates. It was found that okadaic acid was the least potent inhibitor (IC50 approximately 10(-9) M, IC100 approximately 10(-6) M), while the other compounds exhibited IC50 values of approximately 5 x 10(-10) M and IC100 approximately 5 x 10(-9) M. The findings indicate that the inhibitory substances employed in this study may be used pharmacologically to investigate the role of serine/threonine PPases in RINm5F cell insulin secretion, a process that is likely to be regulated to a major extent by protein phosphorylation. PMID- 8204805 TI - Arachidonate activation of protein kinase C may be involved in the stimulation of protein synthesis by insulin in L6 myoblasts. AB - Insulin stimulated protein synthesis in L6 myoblasts but did not increase the labelling of DAG or the release of phosphocholine from phosphatidylcholine. The DAG lipase inhibitor, RHC 80267, more than doubled the amount of label appearing in DAG but did not stimulate protein synthesis. Even in the presence of the DAG lipase inhibitor insulin failed to have any effect on DAG labelling, and conversely RHC 80267 did not modify the insulin-induced increase in protein synthesis. These results suggest that endogenous DAG production is not involved in the stimulation of protein synthesis by insulin. However, exogenous diacylglycerols (1-oleoyl-2-acetyl glycerol and 1-stearoyl-2-arachidonoyl glycerol) both stimulated protein synthesis in L6 myoblasts. The efficacy of the former (arachidonate-free) DAG suggested that their action was by activation of protein kinase C rather than by arachidonate release and prostaglandin formation. Ibuprofen, an inhibitor of cyclo-oxygenase failed to block the effects of insulin whereas a second cyclo-oxygenase inhibitor, indomethacin had only a partial inhibitory effect. The protein kinase C (PKC) inhibitor, RO-31-8220, totally blocked the effect of insulin. Since indomethacin is also recognised to inhibit phospholipase A2, the data suggests that insulin acts on protein synthesis in myoblasts by arachidonate activation of PKC. PMID- 8204806 TI - Evaluation of coagulation during cardiopulmonary bypass with a heparinase modified thromboelastographic assay. AB - Thromboelastography (TEG) is a useful method of assessing perioperative coagulation function in patients undergoing cardiac surgery. The presence of significant amounts of heparin in blood samples, however, prevents determination of changes in coagulation function by TEG or introduces artifactual error if samples contain heparin that is not present in vivo. For these reasons, whole blood coagulation function monitoring with TEG has not been feasible during cardiopulmonary bypass (CPB) with heparin anticoagulation. In this study, data obtained from 42 volunteers are presented to describe the effects of heparinase on TEG variables in the presence and absence of heparin. These data indicate that heparinase does not affect TEG parameters of whole blood not containing heparin and reverses the TEG effects of low levels of heparin contamination. Subsequently, 51 patients undergoing coronary artery surgery were studied using a modified TEG assay that incorporates in vitro application of heparinase to allow measurement of TEG parameters before, during, and after CPB. Heparinase-modified TEG assays facilitated diagnosis of heparin contamination in preoperative blood samples and permitted baseline TEG evaluation in patients receiving preoperative heparin infusions. Heparinase-modified TEG assays revealed declines in alpha and MA values during CPB, which persisted and significantly correlated with values after protamine infusion (alpha: r = 0.77, P = 0.001; MA: r = 0.78, P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204807 TI - Systemic heparinization during peripheral vascular surgery: thromboelastographic, activated coagulation time, and heparin titration monitoring. AB - Fifteen patients (9 male, 6 female) undergoing peripheral vascular surgery were monitored during surgery for evidence of subclinical anticoagulation using the activated coagulation time (ACT), thromboelastography (TEG), and heparin titration monitoring. Assessments were made at 30-minute intervals before and after the occlusion clamp. Mean (+/- SD) ACT values preoperatively were 111 (17) seconds, and 10 minutes after 5,000 IU of heparin, the ACT was 264 (57) seconds (P < 0.001). Intraoperatively, there was a significant decline in ACT values at 30 minutes (ACT 228 [50] sec, P < 0.005) and 60 minutes (200 [46] sec, P < 0.001) postheparin. No significant difference in ACT was observed between samples drawn distally and proximally to the clamp. TEG profiles were abolished in all patients immediately following heparinization. However, in 2 patients nearly complete return of the TEG coagulation profile was observed prior to the termination of the procedure and was associated with ACT values less than 160 seconds. The heparin device was unable to accurately monitor heparin elimination at these low doses. Variability of patient response to heparinization necessitates the use of intraoperative monitoring of anticoagulation during peripheral vascular surgery. PMID- 8204809 TI - Assisted circulation without systemic heparinization. AB - The need for improvements in materials and equipment for extracorporeal circulation has been obvious for years. Among the surfaces with biologically active compounds, those with heparin binding have been found sufficiently thromboresistant and particularly suitable for different types of artificial perfusion. Partial left heart bypass (LHBP) was performed in 10 anesthetized, acutely instrumented, and open-chested mongrel dogs (weight 23 to 50 kg) with a servo-controlled roller pump. The pump flow was maintained at 50 mL/kg/min for 6 hours. Heparin surface-coated equipment was used without additional heparin. For LHBP with a standard circuit, the total amount of heparin during the study period was (mean +/- SD) 487 +/- 124 IU/kg. The right atrial, pulmonary artery, and left ventricular end-diastolic pressures, cardiac output, left ventricular output, right and left ventricular stroke work, pulmonary gas exchange, and acid-base balance changed similarly with both systems. Blood loss (204 +/- 78 v 1,240 +/- 586 mL, P < 0.0005), volume substitution requirements (647 +/- 48 v 1,860 +/- 764 mL, P < 0.0025), and oxygen extraction ratio (mean 25.4 to 32.0 v 25.4 to 56.4%, P < 0.025) were significantly lower, and mean aortic pressure (mean 65 to 69 v 62 to 38 mmHg, P < 0.025) and hemoglobin concentration (mean 9.1 to 8.1 v 9.4 to 3.9 g/dL, P < 0.05) were significantly higher during 6 hours of LHBP without systemic heparinization. Low but stable oxygen delivery was provided with heparin-coated LHBP, whereas it showed a descending trend (mean 14.0 to 10.8 v 13.4 to 5.5 mL/kg/min, P < 0.1) with the standard circuit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204808 TI - Assessment of coagulation factor activation during cardiopulmonary bypass with a new monoclonal antibody. AB - Antithrombin-III (AT) is a key inhibitor of blood coagulation that neutralizes activated serine esterases by forming covalent modified complexes (ATm). A new monoclonal antibody directed against short-lived AT-activated serine protease complexes provides a means of measuring subclinical coagulation activity during cardiopulmonary bypass (CPB). Twelve patients undergoing CPB for coronary artery bypass grafting were studied and AT, ATm, D-dimers (DD), and several other coagulation and fibrinolytic markers were measured during the surgical procedure. There were decreases in AT, factors V, II, X, IX, protein S (total and free), C4b binding protein, thrombomodulin, and platelets counts, whereas heparin, ACT, thrombospondin, plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) increased. ATm and the percentage of ATm available (ATm/AT) showed a peak during CPB. These results demonstrate that during CPB, the use of heparin produces an equilibrium involving increased coagulation activation and consumption in association with increased fibrinolysis. The equilibrated consumption of both coagulation and fibrinolytic factors leads to low levels of all factors after cardiac surgery. The ATm assay allows assessment of the differential effects of CPB and surgical trauma on coagulation activation. It is speculated that ATm levels may be useful in monitoring the consumption of coagulation factors. PMID- 8204810 TI - Platelet-induced vasomotion of isolated canine coronary artery in the presence of halothane or isoflurane. AB - To determine the effect of 1.5 MAC of two volatile anesthetics (halothane and isoflurane) on platelet-induced contraction of canine coronary artery, isolated, denuded coronary rings were suspended between two stirrups, placed into organ chambers filled with an oxygenated Krebs-Ringer solution, and connected to an isometric force transducer. Human platelets were obtained from healthy donors and introduced into the organ chambers in increasing amounts to reach 20,50 and, 70 x 10(9) platelets/L. The tension generated in both the control and anesthetic treated rings was recorded; only halothane reduced the tension induced by platelet activation in the organ chambers. In some experiments, aliquots of Krebs Ringer solution were taken to determine the amount of 5-HT and TB2 released by 70 x 10(9) human platelets in the presence and absence of the anesthetics. Only halothane reduced TA2 production by the activated platelets. Finally, the contractile response of isolated denuded canine coronary artery rings to U46619, a thromboxane analog, was measured in the presence and absence of the anesthetics. Neither halothane nor isoflurane attenuated the response. In another series of experiments, in vitro platelet aggregation was induced by epinephrine, collagen, ADP, or arachidonic acid in the presence or absence of 1.5 MAC isoflurane or halothane. Both anesthetics significantly reduced the aggregation. PMID- 8204811 TI - Nitric oxide gives maximal response after coronary artery bypass surgery. AB - The dose-response to inhalation of nitric oxide (NO) after coronary artery bypass surgery was studied in seven patients with normal preoperative lung function and chest radiograms. During postoperative controlled ventilation with PEEP 5 and 10 cmH2O, the patients inhaled NO in concentrations of 2 to 25 ppm, in random order, for 6 to 10 minutes. Hemodynamic and oximetric data were analyzed before, 5 minutes after start of the NO inhalation, and 5 minutes after the cessation. The response was the same at all concentrations; mean pulmonary artery pressure decreased by 11 +/- 1% (P < 0.05) and pulmonary vascular resistance decreased by 22 +/- 2% (P < 0.05). Systemic hemodynamics did not change, but oximetric parameters tended to improve. Changes in PEEP did not affect the response. It is concluded that, in patients who have undergone coronary artery bypass grafting, inhalation of 2 to 25 ppm NO causes a dose-independent decrease in pulmonary artery pressure and pulmonary vascular resistance. In order to investigate the dose-response curve, concentrations lower than 2 ppm of NO must be used. PMID- 8204812 TI - Dichloroacetate enhances myocardial functional and metabolic recovery following global ischemia. AB - This study was undertaken to determine the effect of dichloroacetate (DCA) on myocardial functional and metabolic recovery following global ischemia. Sixteen isolated rabbit hearts were subjected to 120 minutes of mildly hypothermic (34 degrees C) cardioplegic arrest with multi-dose, modified St. Thomas' cardioplegia. Following ischemia, hearts were reperfused with either a physiologic salt solution (PSS) as controls, (CON, N = 10), or PSS containing DCA (DCA, N = 6) at a concentration of 1 mmol/L. Functional and metabolic indices were determined at baseline and at 15, 30, and 45 minutes of reperfusion. Results were analyzed using analysis of variance (ANOVA, Sheffe F test) and significance was defined as P < 0.05. Functional recovery was significantly better in hearts reperfused with DCA. Developed pressure (DP) recovered to 62 +/- 4% of baseline in DCA hearts, compared to 37 +/- 8% in CON hearts. Recovery of dP/dt was also improved in DCA versus CON hearts (67 +/- 5 v 43 +/- 10%). Coronary blood flow was not different between groups either at baseline or during reperfusion, but myocardial oxygen consumption (MVO2) was increased in the DCA versus CON hearts (71 +/- 10% of baseline, v 51 +/- 19%). Diastolic compliance during reperfusion was improved in those hearts receiving DCA, as was myocardial mechanical use efficiency (DP/MVO2). Correction of myocardial tissue pH to baseline values was similar in both groups, indicating that the beneficial effect on functional recovery seen with DCA was not solely related to amelioration of acidosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204813 TI - Intraoperative detection of coronary artery graft occlusion by myocardial contrast echocardiography. PMID- 8204814 TI - Heparin-coated cardiopulmonary bypass circuits. AB - The indications for heparin-coated extracorporeal circuits cannot be defined or limited at present. Clinical investigation remains at an early stage of development. In situations where the risk of systemic anticoagulation is high, this technology would seem to hold great promise. Examples include extracorporeal lung assist and resuscitation from accidental hypothermia. Some have also suggested the use of heparin-coated circuits for percutaneous bypass in cardiopulmonary resuscitation. A significant advantage might also accrue in noncardiac surgical procedures requiring cardiopulmonary bypass, such as complex cerebral aneurysm or arteriovenous malformation resections, resections of the tracheal carina, or bilateral lung transplantations. Its role in routine cardiac surgical procedures remains uncertain, but the work of von Segesser et al suggests a need for continued investigation in that setting using reduced levels of systemic anticoagulation. That endeavor will be greatly assisted by the recent development of heparin-coated cardiotomy reservoirs. Although heparin-coated circuits have been safely used for extracorporeal lung assist with little or no systemic anticoagulation, prospective studies are clearly needed to determine if this approach is advantageous, and it would seem appropriate to develop heparin coating for silicone-based membrane oxygenators. PMID- 8204815 TI - Case 2--1994. Management of a cardiac pheochromocytoma in two patients. PMID- 8204816 TI - Pro: autologous blood should be available for elective cardiac surgery. PMID- 8204817 TI - Con: autologous blood collection is not useful for elective coronary artery bypass graft surgery. PMID- 8204818 TI - An unusual capnograph tracing. PMID- 8204819 TI - Serum platelet-activating factor acetylhydrolase during coronary artery bypass surgery. PMID- 8204820 TI - Looping of a subclavian catheter: an unusual presentation. PMID- 8204821 TI - Continuous axillary block for ischemia following failed radial artery cannulation. PMID- 8204822 TI - Molecular analysis of the aspartate kinase-homoserine dehydrogenase gene from Arabidopsis thaliana. AB - The gene encoding Arabidopsis thaliana aspartate kinase (ATP:L-aspartate 4 phosphotransferase, EC 2.7.2.4) was isolated from genomic DNA libraries using the carrot ak-hsdh gene as the hybridizing probe. Two genomic libraries from different A. thaliana races were screened independently with the ak probe and the hsdh probe. Nucleotide sequences of the A. thaliana overlapping clones were determined and encompassed 2 kb upstream of the coding region and 300 bp downstream. The corresponding cDNA was isolated from a cDNA library made from poly(A)(+)-mRNA extracted from cell suspension cultures. Sequence comparison between the Arabidopsis gene product and an AK-HSDH bifunctional enzyme from carrot and from the Escherichia coli thrA and metL genes shows 80%, 37.5% and 31.4% amino acid sequence identity, respectively. The A. thaliana ak-hsdh gene is proposed to be the plant thrA homologue coding for the AK isozyme feedback inhibited by threonine. The gene is present in A. thaliana in single copy and functional as evidenced by hybridization analyses. The apoprotein-coding region is interrupted by 15 introns ranging from 78 to 134 bp. An upstream chloroplast targeting sequence with low sequence similarity with the carrot transit peptide was identified. A signal sequence is proposed starting from a functional ATG initiation codon to the first exon of the apoprotein. Two additional introns were identified: one in the 5' non-coding leader sequence and the other in the putative chloroplast targeting sequence. 5' sequence analysis revealed the presence of several possible promoter elements as well as conserved regulatory motifs. Among these, an Opaque2 and a yeast GCN4-like recognition element might be relevant for such a gene coding for an enzyme limiting the carbon-flux entry to the biosynthesis of several essential amino acids. 3' sequence analysis showed the occurrence of two polyadenylation signals upstream of the polyadenylation site. This work is the first report of the molecular cloning of a plant ak-hsdh genomic sequence. It describes a promoter element that may bring new insights to the regulation of the biosynthesis of the aspartate family of amino acids. PMID- 8204823 TI - A cereal haemoglobin gene is expressed in seed and root tissues under anaerobic conditions. AB - Legumes, and a very few non-legume plant species, are known to possess functioning haemoglobin genes. We describe here the characterization of a haemoglobin cDNA isolated from barley. The deduced amino acid sequence shows 71% amino acid identity with a non-legume haemoglobin gene, a further 16% of the residues being conservative replacements. The barley cDNA also hybridizes to genomic sequences in rye, maize and wheat. The demonstration of a gene from a monocotyledon with close sequence homology to the known non-legume plant haemoglobins fills a major gap in the known distribution of haemoglobin genes in the plant kingdom. The expression of the gene is induced in isolated barley aleurone layers exposed to anaerobic conditions, and the roots of flooding stressed barley plants. The expression of the RNA under anoxic conditions is similar to that of a known anaerobic response gene, alcohol dehydrogenase. Our results suggest that the increased expression of haemoglobin RNA is an integral part of the normal anaerobic response in barley. The findings are discussed in the light of current theories of haemoglobin function and evolution. PMID- 8204824 TI - Meristem-specific gene expression directed by the promoter of the S-phase specific gene, cyc07, in transgenic Arabidopsis. AB - A genomic clone for the cyc07 gene, which is expressed specifically at the S phase during the cell cycle in synchronous cultures of periwinkle (Catharanthus roseus) cells, was isolated. Determination of the nucleotide sequence of the clone revealed that the cyc07 gene consists of seven exons separated by six introns. Genomic Southern analysis indicated that the cyc07 gene is present as a single copy per haploid genome in periwinkle. Expression of related genes was detected in a wide range of other plants. Transgenic Arabidopsis plants were generated that expressed the gene for beta-glucuronidase (GUS) under the control of the promoter of the cyc07 gene. The tissue-specific pattern of expression directed by the promoter was investigated by analysis of GUS activity. Histochemical tests demonstrated that 589 bp of the 5'-upstream sequence of the cyc07 gene could direct specifical expression of the GUS reporter gene in meristematic tissues in transgenic plants. The spatial pattern of expression directed by the promoter was closely correlated with meristematic activity and cell proliferation, suggesting an association between the function of the cyc07 gene and cell proliferation. PMID- 8204825 TI - Low-temperature-responsive barley genes have different control mechanisms. AB - Several low-temperature-responsive (LTR) genes from barley have been shown to have high steady-state transcript levels. Run-on transcription was used to determine the control of expression of these LTR genes. Six of these are shown to be transcriptionally regulated (blt 4/9, blt 101, blt 1015, blt 63, blt 49, blt 410) whilst three are post-transcriptionally regulated (blt 14, blt 411, blt 801). Two transcriptionally regulated genes (blt 4/9 and blt 101) and one post transcriptionally regulated gene (blt 14) have been used in expression studies. The time course for the appearance and decay of these transcripts is given. Initial appearance and steady-state levels of individual transcripts have different temperature characteristics but no single gene correlates with the cold acclimation response. We suggest that these different response profiles may represent a means of fine-tuning the low-temperature response. One gene, blt 4/9, also accumulated high steady-state levels of transcript in response to drought and a nutrient stress. However, only drought has an acclimating effect on barley plants. PMID- 8204827 TI - Cloning and characterization of Tag 1, a tobacco anther beta-1,3-glucanase expressed during tetrad dissolution. AB - A critical stage in pollen development is the dissolution of the four products of meiosis, the tetrads, into free microspores. The tetrads are surrounded by a thick callose wall composed of beta-1,3-glucan. At the completion of meiosis, the tetrads are released into the anther locule after hydrolysis of the callose by a beta-1,3-glucanase. Using the polymerase chain reaction, we have amplified and subsequently cloned a cDNA corresponding to a beta-1,3-glucanase, tobacco (Nicotiana tabacum cv. Samsun) anther glucanase (Tag 1), which is expressed exclusively in anthers from meiosis to the free microspore stage of pollen development. The identity of the clone was determined by DNA and deduced protein sequence similarity to other known beta-1,3-glucanases. Several regions strictly conserved among four classes of glucanases are also conserved in the Tag 1 protein. Tag 1 represents a novel class of beta-1,3-glucanase based on phylogenetic analysis and RNA expression pattern. Tag 1 RNA was detected in situ only in the tapetum, with maximal expression just prior to tetrad dissolution. Due to its expression pattern and sequence similarity to other beta-1,3 glucanases, we believe Tag 1 may be involved in tetrad dissolution. PMID- 8204826 TI - The tRNA(Ser)-isoacceptors and their genes in Nicotiana rustica: genome organization, expression in vitro and sequence analyses. AB - The existence of six serine codons results in a complex pattern of tRNA(Ser) isoacceptors in organisms and organelles. According to the original wobble hypothesis, a minimum of three isoacceptors should be sufficient to read the six serine codons. We have isolated five cytoplasmic tRNAs(Ser) from leaves of Nicotiana rustica. Their nucleotide sequences identify them as four different isoacceptors with the anticodons cm5UGA, CGA, IGA and GCU. For tRNA(Ser) with IGA anticodon, two species have been detected which vary only by one nucleotide in the long extra arm. The first three isoacceptors recognize codons of the type UCN whereas the fourth isoacceptor reads the two serine codons AGC and AGU. The tRNA(Ser) sequences were used to design appropriate primers for the amplification of Nicotiana nuclear tRNA(Ser) genes by the polymerase chain reaction (PCR). A total number of eight tRNA(Ser) genes differing in the coding region were thus identified. Selected PCR DNA fragments were then employed as probes for the isolation of the corresponding genes from a nuclear DNA library of N. rustica. Sequence analyses revealed that five of the isolated seven clones contained tRNA(Ser) genes which are identical in sequence with the five cytoplasmic tRNAs(Ser) mentioned above. None of them contains an intervening sequence. This is the first time that all putative cellular tRNA(Ser) isoacceptors and their corresponding genes have been characterized in an eukaryotic organism. Most of the tRNA(Ser) genes are functional as deduced from in vitro transcription and processing studies. Two of the genes yield pre-tRNAs(Ser) which are not or poorly converted to mature tRNA in a plant extract. The approximate tRNA(Ser) gene number was estimated by hybridization of specific DNA probes to Eco RI-cleaved Nicotiana nuclear DNA. The overall hybridization pattern indicates that members of each particular tRNA(Ser) gene family do not appear to be clustered but distributed randomly throughout the Nicotiana genome. PMID- 8204828 TI - Structural analysis of two length variants of the rDNA intergenic spacer from Eruca sativa. AB - Restriction enzyme analysis of the rRNA genes of Eruca sativa indicated the presence of many length variants within a single plant and also between different cultivars which is unusual for most crucifers studied so far. Two length variants of the rDNA intergenic spacer (IGS) from a single individual E. sativa (cv. Itsa) plant were cloned and characterized. The complete nucleotide sequences of both the variants (3 kb and 4 kb) were determined. The intergenic spacer contains three families of tandemly repeated DNA sequences denoted as A, B and C. However, the long (4 kb) variant shows the presence of an additional repeat, denoted as D, which is a duplication of a 224 bp sequence just upstream of the putative transcription initiation site. Repeat units belonging to the three different families (A, B and C) were in the size range of 22 to 30 bp. Such short repeat elements are present in the IGS of most of the crucifers analysed so far. Sequence analysis of the variants (3 kb and 4 kb) revealed that the length heterogeneity of the spacer is located at three different regions and is due to the varying copy numbers of repeat units belonging to families A and B. Length variation of the spacer is also due to the presence of a large duplication (D repeats) in the 4 kb variant which is absent in the 3 kb variant. The putative transcription initiation site was identified by comparisons with the rDNA sequences from other plant species. PMID- 8204829 TI - Analysis of transgenic tobacco plants expressing a truncated form of a potyvirus coat protein nucleotide sequence. AB - Transgenic Nicotiana tabacum cv. Burley 49 plants were generated which expressed a tobacco etch virus (TEV) coat protein (CP) gene construct containing a stop codon positioned at codon 147. This gene construct was expected to produce a TEV CP lacking the carboxy-terminal 118 amino acids of the full-length 264 amino acid CP. TEV CP gene transcripts of the expected size could be detected in transgenic plants but the expected truncated CP could not be detected. Ten independent transgenic lines expressing this form of the TEV CP gene were examined in detail. Two transgenic plant lines were resistant to aphid- or mechanically transmitted TEV and one line was highly resistant. Protoplasts derived from the highly resistant plant line did not support virus replication. The data suggested that the expression of this mutated form of the TEV CP gene could interfere with TEV replication and displayed features associated with RNA-mediated virus resistance. PMID- 8204830 TI - Structure and expression of a cDNA encoding a histone H2A from Euglena gracilis. AB - Screening of a lambda gt11 cDNA expression library of Euglena gracilis with antibodies directed against histones H2 from maize resulted in the isolation of a full-length cDNA for a histone H2A. The open-reading frame of 408 bp corresponded to a protein of 136 amino acid residues (14 kDa). Despite the presence of a poly(A) tail, which is typical of plant histone mRNA but not of animal histone mRNA, the size of the deduced protein and its percentage of homology were closer to animal histone H2As than to plant or lower eukaryotic histone H2A. Sequence alignment revealed that the Euglena H2A protein was characterized by a shorter C terminus and a N-terminus which extended 10 residues past the animal H2A. In contrast to other organisms studied, the expression of the Euglena H2A gene appeared to be almost constant during an entire life-cycle and presented no cell stage-specific expression during development. Similar results are obtained for another histone gene, H3, and for beta-tubulin. Regulation of gene expression at a post-transcriptional level seems to be a general feature of Euglena. PMID- 8204831 TI - Molecular analysis of wild-type and mutant alleles at the Opaque-2 regulatory locus of maize reveals different mutations and types of O2 products. AB - The expression of the various members of the zein multigene family in maize endosperm is controlled by different regulatory loci. One of these loci, Opaque 2, coding for a bZIP transcriptional factor, controls the expression of a subset of zein genes. Analysis of genomic DNA from plants carrying wild-type (O2) or mutant o2 alleles shows specific DNA restriction patterns that correlate with transcript types and their various gene products. Northern and western analyses show the presence in different wild types of a 1.7 kb transcript coding for different sizes of normal O2 proteins that migrate as doublets in the 68-72 kDa range. Among the various o2 mutants analysed we showed the occurrence of various null-transcript alleles, the presence of alleles with a normal size transcript which, however, produce a different-sized o2 protein, and a mutant producing both a normal size transcript and a longer transcript, but generating only a single o2 product migrating around 40 kDa. Analysis of other mutations (o7, fl2) known to affect zein polypeptide synthesis shows no interference of these mutations in the expression of the O2 gene products. The overall results indicate the occurrence of micro heterogeneity in the O2 wild-type genes and a broad spectrum of o2 mutations, both producing different sizes of O2 or o2 proteins. A nomenclature of the O2 and o2 genes based on the RFLP, transcripts and products of the various alleles is presented. PMID- 8204832 TI - Characterization and accumulation pattern of an mRNA encoding an abscission related beta-1,4-glucanase from leaflets of Sambucus nigra. AB - A cDNA library was produced using mRNA extracted from ethylene-treated leaflet abscission zones of common elder (Sambucus nigra). Screening of the library with the insert from pBAC10, which encodes an abscission beta-1,4-glucanase (cellulase) from bean (Phaseolus vulgaris), resulted in the isolation of a near full-length cDNA which was designated JET 1. Northern analysis, using JET 1 as a probe, detected a transcript of 1.9 kb that accumulated prior to the first visible signs of cell separation. Accumulation of the JET 1 transcript is promoted by ethylene and primarily restricted to the tissue comprising the abscission zone. Sequence analysis of JET 1 indicates it is 1768 bp in length and shares significant homology at the amino acid level with beta-1,4-glucanases from the leaf abscission zone of P. vulgaris (67%) and ripening avocado fruit (48%). The predicted peptide sequence of the S. nigra enzyme contains two potential glycosylation sites. Genomic Southern analysis of S. nigra DNA reveals that JET 1 may belong to a multi-gene family. PMID- 8204833 TI - Nucleotide sequence of a rice cDNA similar to a maize NADP-dependent malic enzyme. AB - We have isolated a rice cDNA clone that is homologous to the gene for the maize NADP-dependent malic enzyme (EC 1.1.1.40; NADP-ME). The deduced amino acid sequence coded for by the cDNA indicates a high level of homology to chloroplast type NADP-ME, including a transit peptide with pronounced hydrophobic properties at the amino terminus. Northern blot analysis indicates that the expression of this gene is regulated by external stress such as submergence. PMID- 8204834 TI - Sequence of a plant cDNA from Vicia faba encoding a novel Ran-related GTP-binding protein. AB - A clone obtained from a broad bean (Vicia faba) developing cotyledon cDNA library contained the complete coding sequence of a polypeptide with very high homology to the small GTP-binding proteins Ran from human cells and Spi1 from yeast. These proteins belong to the ras superfamily of proteins involved in different basic cellular processes. The Ran/Spi1 proteins interact with a protein bound to DNA (RCC1) and are thought to function in the regulation of the cell cycle. The amino acid sequence of the obtained plant Ran-homologue, designated Vfa-ran, is 74% and 76% identical to Ran and Spi1, respectively. The five functional, conserved domains of ras-related proteins are present in the Vfa-ran sequence. However, as in Ran/Spi1 the C-terminus of Vfa-ran is very acidic and lacks the Cys motif for isoprenylation. Northern blotting revealed a corresponding mRNA expression in broad bean roots, leaves, and cotyledons with the highest level in roots. PMID- 8204835 TI - [Character of kinesthetic and somatosensory evoked potentials in patients with Parkinsonism syndrome]. PMID- 8204836 TI - [Decrease in motor activity in C57Bl/6 mice as affected by lymphocytes taken from animals with Parkinsonian syndrome induced by 1,2,3,6-tetrahydropyridine (MPTP)]. PMID- 8204837 TI - [Effect of ischemia on development of deafferentation pain syndrome and microcirculation disorders in rats]. PMID- 8204838 TI - [Involvement of the gastric mucosa in rats of various lines in acute emotional stress: protective effect of interleukin-1beta]. PMID- 8204839 TI - [Dynamics of platelet serotonin levels in affective disorders]. PMID- 8204840 TI - [Changes in the rate of cholesterol synthesis in lymphocytes, and blood lipid and lipoprotein levels in patients with ischemic heart disease and hypercholesterolemia during treatment with lovastatin and obsidan]. PMID- 8204841 TI - [Connective tissue generated mechanical stress during contraction of the vessel wall]. PMID- 8204842 TI - [A model of dosed acute sublethal microwave thermal stress]. PMID- 8204843 TI - [Neutrophilokines as inducers of stress]. PMID- 8204844 TI - [Changes in cytochrome P-450 and NADPH-cytochrome P-450 reductase in hereditary retinal degeneration in rats]. PMID- 8204845 TI - [Hypolipidemic action of 6-oxa-D-homo-8-izoestrone and its methyl ester]. PMID- 8204846 TI - [Effect of tafcin on the functional activity and intracellular pH of mouse peritoneal macrophages]. PMID- 8204847 TI - [Characterization of binding sites for high-density lipoproteins in cultures of parenchymal, endothelial and Kupffer cells of rat liver]. PMID- 8204848 TI - [Effect of prolonged intake of lovastatin on the number of glucocorticoid receptors in peripheral blood lymphocytes]. PMID- 8204849 TI - [Relationship between reactions of the systemic arterial pressure, constriction of skeletal muscle arterioles and changes in the linear blood velocity in them during administration of noradrenaline in rats after general gamma-irradiation with a dose of 1 Gy]. PMID- 8204850 TI - [Regulation of the adenylate cyclase system of the rat lungs in Yersinia pestis intoxication]. PMID- 8204852 TI - [Evoked cutaneous sympathetic potential in bronchial asthma patients with hyperventilation syndrome]. PMID- 8204851 TI - [Dissociation of effector:target conjugates in the mechanism of activation of human natural killers by factors acting at the stage of the "lethal impact"]. PMID- 8204853 TI - [Regularities of age-related variability in autoantibody levels in mice (NZB X NZW)F1]. PMID- 8204854 TI - [Effect of thymosin fractions on the development of toxic edema-swelling of the brain]. PMID- 8204855 TI - [Preparing bifunctional antibodies to human IGG and horseradish peroxidase and their utilization for testing of antibodies to HIV]. PMID- 8204856 TI - [Pharmacokinetics of (125I)3-deoxy-3-iodo-glucose in experimental tumor models in vivo]. PMID- 8204857 TI - [Dynamics of binding of various prostanoids in mouse serum with spontaneous metastatic Lewis lung carcinoma; effect of exogenous prostaglandins on dissemination of the tumor]. PMID- 8204858 TI - [Mechanism of specific suppression of stimulated chemiluminescence of polymorphonuclear leukocytes in allergic processes]. PMID- 8204859 TI - [Interrelationship between membrane potential of adrenocorticocytes and functional activity of adrenals in adult and aged rats]. PMID- 8204860 TI - [Age-related features of the effect of insulin on secretion of somatotropic hormone]. PMID- 8204861 TI - [Liver cell ultrastructure of various herbivorous animals]. PMID- 8204862 TI - [Effect of laser irradiation on proliferative activity of cells in culture]. PMID- 8204863 TI - [Effect of the drug no-spa on the status of the arterioles in rat skeletal muscles after total gamma-irradiation with a dose of 1 Gy]. PMID- 8204864 TI - [Ultrastructural changes in the microcirculatory bed and nerve cells of the midbrain reticular formation of rats with hypertensive response during immobilization emotional stress]. PMID- 8204865 TI - [Automyoneoventricles (AMNV)--new possibilities in the surgical treatment of terminal cardiac insufficiency(experimental study)]. PMID- 8204866 TI - [Engineering methods for quality control of localization of muscle and cardial electrodes in the process of performance of the cardiomyoplasty operation]. PMID- 8204867 TI - [A method for analysis for the "dose-effect" in multifactorial medico-biological experiments]. PMID- 8204868 TI - [Mechanism of development of bacteria in the log-phase]. PMID- 8204869 TI - Cellular receptors for the plasminogen activators. PMID- 8204870 TI - Myelodysplastic syndrome after autologous transplantation for lymphoma: the price of progress. PMID- 8204871 TI - No evidence for genomic imprinting of the human BCR gene. AB - Chronic myeloid leukemias and 5% to 20% of acute lymphoid leukemias are characterized by the Philadelphia chromosome, a reciprocal chromosomal translocation, t(9;22)(q34;q11), generating BCR-ABL and ABL-BCR fusion genes. Cytogenetic studies have recently shown a preferential involvement of the paternally derived chromosome 9 and the maternally derived chromosome 22 in this translocation, indicating that imprinting might be involved in the formation or selection of the translocation. In this study, we have identified a BamHI polymorphism in the coding region of BCR exon 1, allowing us to investigate whether both BCR alleles are transcribed. By using a reverse transcriptase polymerase chain reaction assay, we show that both BCR alleles are expressed in the peripheral blood cells of normal individuals. PMID- 8204872 TI - Paternal origin of the rearranged major breakpoint cluster region in chronic myeloid leukemia. AB - The Philadelphia chromosome, t(9;22), is present in virtually all cases of chronic myeloid leukemia (CML). It has previously been shown by cytogenetic studies that the rearranged chromosome 22 in patients with CML is exclusively maternal in origin. To address this issue at a molecular level, the major breakpoint cluster region (M-bcr) on chromosome 22 was examined using Southern blot assays and M-bcr Pvu II and Mae II restriction site polymorphisms in three CML patients. In all three cases, the rearranged allele was paternal in origin. These results indicate that the paternally derived M-bcr allele may also be involved in the M-bcr rearrangement. PMID- 8204873 TI - Genomic instability of microsatellite repeats and its association with the evolution of chronic myelogenous leukemia. AB - Tumorigenesis has been shown to proceed through a series of genetic alterations involving protooncogenes and tumor-suppressor genes. Investigation of genomic instability of microsatellites has indicated a new mechanism for human carcinogenesis in hereditary nonpolyposis colorectal cancer and sporadic cancer and this instability has been shown to be related to inherited predisposition to cancer. This study was conducted to determine whether such microsatellite instability is associated with the evolution of chronic myelogenous leukemia (CML) to the blast crisis. Nineteen CML patients clinically progressing from the chronic phase to accelerated phase or blast crisis and 20 other patients in the CML chronic phase were studied. By polymerase chain reaction assay, DNAs for genomic instability in five separate microsatellites in chromosome arms 5q (Mfd27), 17p (Mfd41), 18q (DCC), 3p (CI3-9), and 8p (LPL) were examined. Differences in unrelated microsatellites of chronic and blastic phase DNAs in 14 of 19 patients (73.7%) were demonstrated. Somatic instability in five microsatellites, Mfd27, Mfd41, DCC, CI3-9, and LPL, was detected in 2 of 19 (10.5%), 8 of 19 (42.1%), 11 of 19 (57.9%), 4 of 17 (23.5%), and 4 of 17 (23.5%) cases. In 10 of 19 cases (52.6%), genetic instability in at least two of five microsatellites was observed and was categorized as replication error (RER+) phenotype. CML evolution cases with myeloid, lymphoid, and mixed phenotypes and the blast crisis and accelerated phase showed somatic instability in a number of microsatellites. No alterations in leukemic cells at the chronic phase could be detected in any microsatellites. These data indicate instability of microsatellites (RER+) but not familial predisposition to possibly be a late genetic event in the evolution of CML to blast crisis. In the microsatellite of the DCC gene, complicated alterations in band patterns caused by instability as well as loss of heterozygosity (LOH) were observed in 13 of 19 cases (68.4%): instability in 9 cases, instability plus LOH in 2 cases, and only LOH in 2 cases. These highly frequent alterations in microsatellites, including instability and LOH, suggesting that secondary events due possibly to loss of fidelity in replication and repair machinery may be significantly associated with CML evolution. PMID- 8204874 TI - The gamma subunit of the interleukin-2 receptor is expressed in human monocytes and modulated by interleukin-2, interferon gamma, and transforming growth factor beta 1. AB - The interleukin-2 receptor gamma (IL-2R gamma) chain is a newly recognized component of the IL-2R of lymphoid cells that is required for their response to IL-2. We investigated the expression of IL-2R gamma protein in human monocytes by Western blot analysis using an antiserum specific for IL-2R gamma. We found that IL-2R gamma subunit is constitutively expressed in human monocytes and upregulated by the monocyte-activating factors IL-2 and interferon gamma (IFN gamma). Furthermore, we show that transforming growth factor beta 1 (TGF beta 1) downmodulates, in a dose-dependent manner, basal and IL-2-induced, but not IFN gamma-induced, IL-2R gamma chain expression, and this effect may be responsible for TGF beta 1 suppressive activity on IL-2-activated monocytes. Overall, these results show that the expression of the IL-2R gamma subunit in human monocytes is tightly regulated by the cytokine network, suggesting a critical role played by this protein on monocyte activation. PMID- 8204875 TI - Importance of effective central nervous system therapy in isolated bone marrow relapse of childhood acute lymphoblastic leukemia. BFM (Berlin-Frankfurt-Munster) Relapse Study Group. AB - Presymptomatic central nervous system (CNS) treatment in children with a late isolated first bone marrow (BM) relapse of acute lymphoblastic leukemia (ALL) was based on intermediate-dose systemic and intrathecal (IT) methotrexate (MTX) in the multicenter trial, ALL-REZ BFM 85. Because this was associated with an excess of overt second CNS relapses, cranial radiotherapy (cRT) plus prolonged triple IT therapy with MTX, cytarabine, and prednisone was instituted during the course of the subsequent trial, ALL-REZ BFM 87. Results of children with or without cRT, but otherwise identical chemotherapy, are presented here. Between April 1985 and March 1990, 93 children with their first late isolated BM relapse of ALL were entered on protocols ALL-REZ BFM 85M and ALL-REZ BFM 87. An intensive 6-month phase of multiagent chemotherapy that included 8 courses of systemic MTX (1 g/m2) plus IT MTX was followed by 2 years of conventional maintenance therapy with daily 6-thioguanine and biweekly MTX. Children with bone marrow transplantation excluded, 73 were in complete remission at the end of intensive polychemotherapy, 40 of whom received fractionated cRT plus triple IT therapy during the following 6 months; 11 did not receive cRT but prolonged triple IT; 22 received neither cRT nor prolonged triple IT. Except for a higher percentage of children who had received cRT in front-line protocols (29 of 33 v 20 of 40), the patient groups without or with salvage cRT were comparable. Of 33 children without salvage cRT, 26 relapsed, compared with 21 of 40 who had received cRT (P < .05). The difference was solely attributable to second relapses with CNS involvement (10 of 33 v 1 of 40; P < .01). Estimated 6-year event-free survival rates were .18 for children without cRT and .46 for children with cRT (P < .01). In patients without cRT, no impact of prolonged IT therapy could be shown. The data suggest that second CNS prophylaxis with cRT and prolonged triple IT therapy in children with late isolated BM relapse of ALL is effective in preventing CNS relapses, in reducing the overall relapse rate, and in increasing the overall survival rate. PMID- 8204876 TI - Phase I study of recombinant interleukin-1 beta in patients undergoing autologous bone marrow transplant for acute myelogenous leukemia. AB - A phase I trial was conducted with recombinant human interleukin-1 beta (rhIL-1 beta) in patients undergoing autologous bone marrow (BM) transplantation for acute myelogenous leukemia. rhIL-1 beta was administered at 3 dose levels (0.01, 0.02, 0.05 microgram/kg) by 30 minute intravenous infusion once a day beginning on the day of BM infusion and continuing for a total of 5 doses. A total of 17 patients were entered on the trial, and their results were compared with those of 74 consecutive historical control patients that did not receive colony stimulating factors. Moderate toxicity was observed in all patients. All 17 patients developed fever and chills within 30 minutes after initiation of rhIL-1 beta, and hypotension was observed in 14 of 17 patients 5 to 8 hours after the infusion. A total of 30% of patients required therapy (normal saline or dopamine) for treatment of hypotension. Therefore, dose escalation was discontinued at the 0.05 microgram/kg dose level. The number of days required to achieve an absolute neutrophil count greater than 500 mL in patients who received rhIL-1 beta was less than in historical patients (25 v 34; P = .02). This appeared to correlate with a reduced incidence of infection between days 0 and 28 after BM infusion (12% v 23%; P = .049). Median bilirubin, median creatinine, platelet recovery, and days in the hospital were not different between study patients and historical controls. Survival of patients who received rhIL-1 beta compared with that of historical patients was improved (30% v 20%; P = .04). These possible benefits were achieved at the cost of moderate toxicity during rhIL-1 beta administration. PMID- 8204877 TI - Identification of residues in the first and fourth helices of human granulocyte macrophage colony-stimulating factor involved in biologic activity and in binding to the alpha- and beta-chains of its receptor. AB - Residues within the first and fourth helices of human granulocyte-macrophage colony-stimulating factor (hGM-CSF) were analyzed for their role in biologic activity and interaction with the alpha- and beta-chains of the hGM-CSF receptor. Within the first helix substitution of the surface residues Glu14, Asn17, Gln20, Arg23, Arg24, and Asn27 or the buried residues Ala18, Leu25, and Leu28 did not significantly impair bioactivity or receptor binding. Substitutions at the buried residues Ala22 and Leu26 had intermediate bioactivity. However, substitutions of the surface residue Glu21 or the buried residue Ile19 reduced the relative bioactivity of the analogues to as little as 0.45% and 0.3%, respectively. Substitution of the charged surface residues of the fourth helix showed that substitution at Glu104, Lys107, and Lys111 had no significant effect on bioactivity, but substitution at Glu108 and Asp112 reduced the potency of the analogues to 34% and 7%, respectively. Receptor binding studies showed that, whereas Glu21 is the critical residue for binding to the hGM-CSF-receptor beta chain, Asp112 is likely to be involved in binding to the GM-CSF-receptor alpha chain. These results establish the relative contribution of residues in the first and fourth helices for GM-CSF bioactivity and receptor binding, and support a model where the fourth helix of GM-CSF interacts with the alpha-chain, and the first helix with the beta-chain of the GM-CSF receptor. PMID- 8204878 TI - Identifying and characterizing casein kinase II in human platelets. AB - We have recently shown that inhibition of protein phosphatases in platelets causes increases in protein phosphorylations with a concomitant inhibition of platelet responses. The burst in protein phosphorylation appears to be catalyzed by messenger-independent protein kinases. The aim of the present study was to characterize the presence of broad families of protein kinases found in platelets. Lysates of control and thrombin-stimulated platelets were prepared, and proteins were separated on MONO Q fast protein liquid chromatography. In addition to the presence of histone protein kinase and tyrosine kinase activities, human platelets contain casein kinase II (CKII) activity as assessed by phosphorylation of a specific substrate peptide. Western blot analysis and immunogold electron microscopy studies further showed the presence of alpha-, alpha'-, and beta-subunits of CKII. The enzyme appears to be distributed throughout the cytosol and not secreted after thrombin treatment. Immunoprecipitation studies suggest that at least some of the holoenzymes exist as an alpha alpha' beta 2 complex. Although no activation of the enzyme was detected after thrombin treatment, our results show that CKII is a major messenger-independent protein kinase in platelets. PMID- 8204879 TI - Severe factor VII deficiency caused by mutations abolishing the cleavage site for activation and altering binding to tissue factor. AB - Factor VII (F.VII) is a vitamin-K-dependent serine protease required in the early stages of blood coagulation. We describe here a patient with severe F.VII deficiency, with a normal plasma F.VII antigen level (452 ng/mL) and F.VII activity less than 1%, who is homozygous for two defects: a G-->A transition at nucleotide 6055 in exon 4, which results in an Arg-->Gln change at amino acid 79 (R79Q); and a G-->A transition at nucleotide 8961 in exon 6, which results in an Arg-->Gln substitution at amino acid 152 (R152Q). The R79Q mutation occurs in the first epidermal growth factor (EGF)-like domain, which has previously been implicated in binding to tissue factor. The R152Q mutation occurs at a site (Arg 152-Ile 153) that is normally cleaved to generate activated F.VII (F.VIIa). Analysis of purified F.VII from patient plasma shows that the material cannot be activated by F.Xa and cofactors. In addition, in an in vitro binding assay using relipidated recombinant tissue factor, patient plasma showed markedly reduced binding to tissue factor at all concentrations tested. In an effort to separate the contributions of the two mutations, three recombinant variants, wild-type, R79Q, and R152Q, were prepared and analyzed. The R152Q variant had markedly reduced activity in a clotting assay, whereas R79Q showed a milder, concentration dependent reduction. The R152Q variant exhibited nearly normal binding in the tissue factor binding assay, whereas the R79Q variant had markedly reduced binding. The time course of activation of the R79Q variant was slowed compared with wild-type. Our results suggest that the first EGF-like domain is required for binding to tissue factor and that the F.VII zymogen lacks activity and requires activation for expression of biologic activity. PMID- 8204880 TI - von Willebrand factor proteolytic processing and multimerization precede the formation of Weibel-Palade bodies. AB - We investigated the intracellular site of pro-von Willebrand factor (pro-vWF) cleavage and multimerization, as well as the fate of the propolypeptide (von Willebrand antigen II) after cleavage. Analysis of subcellular fractions of endothelial cells metabolically labeled with sulfate showed that both cleavage and covalent multimerization occur after sulfation and precede the formation of Weibel-Palade bodies. Because sulfation is a processing step localized to the trans-Golgi network (TGN), our results indicate that multimerization and prosequence cleavage also occur in this organelle. After cleavage, the propolypeptide remains noncovalently associated with the mature vWF subunit. This association is promoted by a high calcium concentration and an acidic pH (conditions thought to prevail in the TGN) and explains the 1:1 stoichiometry of the propolypeptide and mature vWF found in Weibel-Palade bodies. The propolypeptide remains an integral part of the large multimeric vWF aggregates in the Weibel-Palade body until secretion. When secretion occurs under slightly acidic conditions, such as may be found in poorly perfused wounds, the propolypeptide remains associated with the endothelial surface-bound vWF, and may thus participate in the wound healing process. PMID- 8204881 TI - Influence of mutations and size of multimers in type II von Willebrand disease upon the function of von Willebrand factor. AB - We compared the properties of plasma von Willebrand factor (vWF) from normal individuals and from two patients with type IIA (Glu875Lys) and type IIB (duplication of Met 540) von Willebrand disease (vWD) with the corresponding fully multimerized recombinant proteins. We included cryosupernatant from normal human plasma and type IIA plasma (Cys509Arg). Functions of vWF were analyzed by binding assays to platelets in the presence of ristocetin or botrocetin. Parameters of binding (number of binding sites per vWF subunit, and dissociation constant Kd) were quantitatively estimated from the binding isotherms of 125I botrocetin or glycocalicin to vWF, independently of the size of the multimers. We found that ristocetin- or botrocetin-induced binding to platelets was correlated in all cases with the size of vWF multimers. In the absence of inducer, only type IIB rvWF Met-Met540 spontaneously bound to platelets. No significant difference of binding of purified botrocetin to vWF was found between normal and patients' plasma, or between wild-type rvWF (rvWF-WT) and rvWF-Lys875. In contrast, affinity of botrocetin for type IIB rvWF Met-Met540 was decreased. Botrocetin induced binding of glycocalicin to vWF from all plasma and cryosupernatant was similar. Compared with rvWF-WT, binding of glycocalicin to rvWF-Lys875 was normal. In contrast, the affinity for type IIB rvWF Met-Met540 was 10-fold greater. Thus, our data suggest that, in the patients tested, the abnormal IIA phenotype results from the lack of large-sized multimers and is independent of the point mutations. In contrast, the type IIB mutation is directly involved by providing a conformation to the vWF subunits that allows the high molecular weight multimers to spontaneously interact with platelet glycoprotein Ib. PMID- 8204882 TI - The activation-induced decrease in the platelet surface expression of the glycoprotein Ib-IX complex is reversible. AB - Thrombin decreases the platelet surface expression of the glycoprotein (GP) Ib-IX complex. To determine whether this effect is reversible, flow cytometric studies were performed with GPIb-IX-specific monoclonal antibodies. In both whole blood and washed platelet systems, incubation of platelets with thrombin or a combination of adenosine diphosphate and epinephrine resulted in a maximal decrease of the platelet surface expression of GPIb-IX within 5 minutes, after which there was a time-dependent return of the platelet surface GPIb-IX complex, which was maximal by 60 minutes. Exposure of the same platelets to additional exogenous thrombin resulted in a second decrease in platelet surface GPIb-IX, followed by a second reconstitution of platelet surface GPIb-IX. Throughout these experiments there was no measurable release from the platelets of glycocalicin (a proteolytic fragment of GPIb). Experiments in which platelets were preincubated with a biotinylated GPIb-specific MoAb showed that the GPIb molecules that returned to the platelet surface were the same molecules that had been translocated to the intraplatelet pool. The GPIb molecules that returned to the platelet surface were functionally competent to bind von Willebrand factor, as determined by ristocetin-induced platelet agglutination and ristocetin-induced binding of exogenous von Willebrand factor. Inhibitors of protein kinase C and myosin light-chain kinase enhanced the reexpression of platelet surface GPIb. In summary, the activation-induced decrease in the platelet surface expression of the GPIb-IX complex is reversible. Inactivation of protein kinase C and myosin light-chain kinase are important mechanisms in the reexpression of the platelet surface GPIb-IX complex. PMID- 8204883 TI - The loss of Fc gamma RIIIb in paroxysmal nocturnal hemoglobinuria is functionally replaced by Fc gamma RII. AB - Neutrophils from patients with paroxysmal nocturnal hemoglobinuria (PNH) show a deficiency for the glycosylphosphatidylinositol- (GPI) linked Fc gamma receptor IIIb (Fc gamma RIIIb, CD16). The functional consequences of this defect are not clear. Here, we examined Fc gamma RIIIb-deficient neutrophils for their activation via Fc gamma receptors. Hydrogen peroxide (H2O2) production and change of intracellular free calcium [Ca2+]i were used as parameters for cell activation. Fc gamma RII and Fc gamma RIIIb stimulation was reached by cross linking using fragments of monoclonal antibodies or incubation with monoclonal IgG cryoglobulin complexes. In parallel to the deficiency of Fc gamma RIIIb expression, H2O2 production and [Ca2+]i influx were decreased after cross-linking of Fc gamma RIIIb in PNH neutrophils compared with that for normal neutrophils. Stimulation via Fc gamma RII was not affected. Cryoglobulin complexes previously shown to activate normal neutrophils predominantly via Fc gamma RIIIb stimulated PNH neutrophils at a level not significantly weaker than controls. But this activation was mediated only via Fc gamma RII as shown by blocking studies. The results suggest that the loss of GPI-anchored Fc gamma RIIIb is functionally replaced by Fc gamma RII during the immune complex stimulation of PNH neutrophils. Therefore, the equipment of neutrophils with pleomorphic Fc gamma receptors prevents an immunodeficiency in PNH. PMID- 8204885 TI - Growth inhibitory and agonistic signals of interleukin-7 (IL-7) can be mediated through the CDw127 IL-7 receptor. AB - The present study was aimed at identifying surface-membrane molecules involved in the regulation of human B-cell ontogeny. For this purpose, murine monoclonal antibodies (MoAbs) were generated against Pre-Alp, a pre-B acute lymphoblastic leukemia (ALL) cell line, and MoAb R34.34 was selected for further characterization. R34.34 recognized a molecule expressed on normal B-cell precursors (BCP) but not on mature B cells. The antibody also reacted with T lymphocytes, a subpopulation of monocytes from peripheral blood, and a subset of CD34+ cells. Immunoprecipitation analysis indicated that R34.34 recognizes an 80 kD molecular weight antigen. Antibody R34.34 was further found to be directed against an epitope interfering with binding of interleukin-7 (IL-7) to Pre-Alp cells. Expression cloning from a Pre-Alp cDNA library showed that R34.34 antigen is CDw127, the 75- to 80-kD IL-7 receptor. Proliferation of the B-lineage ALL cell lines Reh and Mieliki was inhibited by IL-7, and this effect was specifically reverted by MoAb R34.34. In addition, antibody R34.34 specifically inhibited IL-7-dependent proliferation of normal BCP, Pre-Alp cells, and peripheral T cells. These results imply that both inhibitory and proliferative effects of IL-7 can be mediated through the same receptor on various lineages. R34.34 antibody should be important for the analysis of signal transduction through CDw127. PMID- 8204884 TI - Molecular characterization of CD30+ anaplastic large-cell lymphoma: high frequency of c-myc proto-oncogene activation. AB - Anaplastic large-cell lymphoma (ALCL) represents a morphologically distinct type of non-Hodgkin's lymphoma (NHL) characterized phenotypically by the expression of the CD30 antigen, a new member of the nerve growth factor gene family. The lymphoid origin of ALCL has been documented using immunohistochemical and molecular genetic analyses. However, very little is known so far regarding the precise pathogenetic mechanisms involved in its development and progression. Therefore, we investigated bcl-2, p53, and retinoblastoma gene (Rb) expression immunohistochemically; the occurrence of bcl-2, c-myc, and Rb gene rearrangements using Southern blotting; and the presence of ras and p53 gene somatic mutations by single-strand conformation polymorphism assay in a panel of 18 well characterized ALCLs. In addition, the presence of Epstein-Barr (EBV) and human T cell lymphotropic virus type I (HTLV-I) genomes were investigated using polymerase chain reaction. We identified abnormal c-myc gene products in 6 of 18 cases (33%) of ALCL. On the other hand, the bcl-2 and Rb genes were not rearranged and K-, N-, and H-ras gene somatic mutations were not found. Significant levels of p53 protein expression were found in more than 60% of ALCLs, but only a single ALCL carried a p53 gene mutation (exon 5). Only 3 ALCL cases, all occurring in human immunodeficiency virus-infected patients, were positive for EBV genomes. On the other hand, contrary to previous findings, no HTLV-I products could be identified. Despite the fact that the c-myc proto oncogene appears to be frequently altered in ALCL, no pathognomonic abnormality could be identified and therefore additional studies and new strategies should be designed to identify the pathogenetic mechanisms involved in the development of ALCL. PMID- 8204886 TI - Mechanisms regulating the mRNA levels of interleukin-5 and two other coordinately expressed lymphokines in the murine T lymphoma EL4.23. AB - The mechanisms that regulate the mRNA levels of interleukin-5 (IL-5) were compared with those regulating the mRNA levels of two other coordinately expressed lymphokines in the murine T lymphoma EL4.23. Our results indicate that IL-5 mRNA levels are independently regulated from those of IL-2 and granulocyte macrophage colony-stimulating factor (GM-CSF) mRNAs. The induction of IL-5 mRNA by phorbol 12-myristate 13-acetate (PMA) stimulation was found to be cyclosporin A-resistant, in contrast to the induction of IL-2 and GM-CSF mRNAs. Although the three lymphokine mRNAs were not detected in unstimulated cells by Northern blot analysis, the GM-CSF gene was found by nuclear run-off analysis to be constitutively transcribed. However, the IL-2 and IL-5 genes were transcriptionally inactive in the absence of PMA stimulation. The induction of IL 5 mRNA by PMA stimulation primarily involved increased transcriptional activity. In contrast, GM-CSF mRNA induction predominantly involved enhanced mRNA stability. Both transcriptional and mRNA stabilization mechanisms appeared to regulate IL-2 mRNA induction. The activation of IL-2 and IL-5 gene transcription was dependent on de novo protein synthesis. Cellular treatment with cycloheximide enhanced IL-2 gene transcription once activation was initiated, implicating the involvement of a labile repressor(s). Furthermore, IL-5 mRNA was more stable than IL-2 and GM-CSF mRNAs. These latter two species were stabilized by cycloheximide, suggesting that a labile mechanism may regulate their degradation. PMID- 8204887 TI - BCR-ABL protein expression in peripheral blood cells of chronic myelogenous leukemia patients undergoing therapy. AB - Chronic myelogenous leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome (Ph1) in more than 95% of these patients. The Ph1 and the resulting BCR-ABL fused genes are markers for this type of leukemia. In CML, the product of the fused BCR-ABL gene is typically a protein of approximately 2,000 amino acids termed P210 BCR-ABL. We have developed an assay for the BCR-ABL protein involving Western blotting of circulating white blood cells (WBC) with an anti-ABL monoclonal antibody that can detect P210 BCR-ABL and P145 ABL in peripheral blood cells from chronic phase Ph1-positive leukemia patients. This assay was used to analyze the BCR-ABL protein content of circulating WBC from CML patients before and after various treatments. In parallel to changes in percentages of Ph1-positive blood cells as determined by cytogenetic analyses of bone marrow samples, BCR-ABL protein expression in blood cells decreased or increased as patients entered remission or underwent relapse. Of interest, six Ph1-negative CML patients were BCR-ABL protein-positive. All except one had a rearrangement in the major breakpoint cluster region and that patient expressed P185 BCR-ABL and not P210. Our results indicate that the BCR ABL Western blotting assay has clinical applications for both diagnosis and prospective evaluation of Ph1-positive and Ph1-negative CML patients. PMID- 8204888 TI - Regulation of 92-kD gelatinase release in HL-60 leukemia cells: tumor necrosis factor-alpha as an autocrine stimulus for basal- and phorbol ester-induced secretion. AB - Matrix metalloproteinase 9 (MMP-9), also known as 92-kD type IV collagenase/gelatinase, is believed to play a critical role in tumor invasion and metastasis. Here, we report that MMP-9 was constitutively released from the human promyelocytic cell line HL-60 as determined by zymographic analysis. Tumor necrosis factor-alpha (TNF-alpha) enhanced the enzyme release threefold to fourfold and the protein kinase C (PKC) activator and differentiation inducer 12 O-tetradecanoylphorbol-13-acetate (TPA) eightfold to ninefold. Gelatinase induction by TNF-alpha and TPA was inhibited by actinomycin D or cycloheximide, indicating that de novo protein synthesis was required. Neutralizing monoclonal antibodies to TNF-alpha (anti-TNF-alpha) decreased the basal MMP-9 release of these cells. In addition, these antibodies also significantly interfered with the TPA-induced enzyme release. Agents that inhibit TNF-alpha expression in HL-60 cells, such as pentoxifylline and dexamethasone, completely abrogated both the constitutive and TPA-evoked MMP-9 release. Diethyldithiocarbamate, which is known to stimulate TNF-alpha production in HL-60 cells, exerted a positive effect on MMP-9 release in untreated cells but was inhibitory in TPA-treated HL-60 cells. The PKC inhibitor staurosporine at low concentrations (100 ng/mL) caused a significant augmentation of MMP-9 release in untreated cultures that was blocked by the addition of anti-TNF-alpha. High concentrations (2 mumol/L) of staurosporine completely abolished the extracellular enzyme activity both in untreated and TPA-stimulated cells. These results suggest, that TNF-alpha is required for basal and PKC-mediated MMP-9 release in HL-60 leukemia cells. Thus, MMP-9 secretion may be regulated by TNF-alpha not only in a paracrine but also in an autocrine fashion. This may potentiate the matrix degradative capacity of immature leukemic cells in the processes of bone marrow egress and the evasion of these cells into peripheral tissue. PMID- 8204889 TI - Similar patterns of V kappa gene usage but different degrees of somatic mutation in hairy cell leukemia, prolymphocytic leukemia, Waldenstrom's macroglobulinemia, and myeloma. AB - To compare V kappa gene usage and the amount of somatic mutation in rearranged Ig genes from patients with lymphoproliferative disorders, we have polymerase chain reaction-amplified and sequenced a total of 26 V kappa genes from a total of 55 cases. Six sequences were obtained both from six cases of prolymphocytic leukemia (PLL) and from nine cases of hairy cell leukemia (HCL). Seven sequences were obtained both from 11 cases of Waldenstrom's macroglobulinemia (WM) and 29 cases of multiple myeloma (MM). Eleven different germline genes have been used in this series, indicating a wide but nonrandom usage of germline Ig gene rearrangements in these disorders. Comparison of the nucleotide sequences of V kappa genes obtained from B-cell malignancies with germline V kappa genes shows that somatic mutation is rare in PLL and HCL and common in WM and MM. Analysis of the pattern of mutations suggests that WM and MM are derived from B cells that have been selected by antigen at a relatively late stage of differentiation. PMID- 8204890 TI - Reproducible obtaining of human myeloma cell lines as a model for tumor stem cell study in human multiple myeloma. AB - We report a novel, reproducible methodology which enabled 10 human myeloma cell lines (HMCL) to be obtained from each of 10 tumor samples harvested from 9 patients with extramedullary proliferation. Fresh samples were cultured with interleukin 6 (IL-6) and granulocyte macrophage-colony stimulating factor (GM CSF) at a high cell density and resulting HMCL growth became progressively dependent on IL-6 alone, no longer requiring GM-CSF. These HMCL, which had the same immunoglobulin gene rearrangements as the patients' original myeloma cells, were designated XG-1 to XG-9. XG HMCL had a plasma cell morphology, expressed plasma cell antigen (Ag), namely cytoplasmic immunoglobulins, CD38, B-B4 Ag, and CD77, and lacked the usual B-cell Ag. They also expressed activation antigens such as CD28 with coexpression of CD28 and its ligand, B7 Ag, in four HMCL. Six HMCL expressed CD40, 4 CD23, and 5 its ligand, CD21. The XG HMCL bore adhesion molecules VLA-4 and CD44 (all 10 HMCL), VLA-5 (7 HMCL), and CD56 (4 HMCL). Finally, cytogenetic study of 8 HMCL indicated a 14q+ chromosome, and t(11,14) translocation was found in 6 of 8 and 5 of 8 HMCL, respectively. The possibility of obtaining malignant plasma cell lines reproducibly from each patient with extramedullary proliferation offers a unique tool for studying the phenotype and abnormalities of the still unidentified tumor stem cell in this disease. PMID- 8204891 TI - Splenic lymphoma with villous lymphocytes: analysis of BCL-1 rearrangements and expression of the cyclin D1 gene. AB - The translocation t(11;14)(q13;q32) occurs in about 15% of patients with splenic lymphoma with villous lymphocytes (SLVL) or the closely related disorder lymphoplasmacytic lymphoma (LPL). To characterize the nature and frequency of rearrangements of the BCL-1 locus in SLVL/LPL and to document the effect of these genetic alterations on the expression of the cyclin D1 gene, we analyzed 22 cases of SLVL/LPL with defined cytogenetic abnormalities by both conventional electrophoresis (CE) and pulse-field gel electrophoresis (PFGE) and by Northern blotting. Four SLVL/LPL cases showed rearrangement of the BCL-1 locus. In two cases with t(11;14)(q13;q32), different breakpoints were identified; one mapped adjacent to the major translocation cluster (MTC) and the other within a 28-kb region telomeric of it. In a third case of SLVL with no cytogenetic abnormality of 11q13, a novel breakpoint approximately 100 kb centromeric of MTC was detected by PFGE. The fourth case, which had a normal karyotype, demonstrated rearrangement with a BCL-1 probe immediately telomeric of MTC. This case may have had a small deletion of 0.5 kb from within the BCL-1 locus. No rearrangement of the BCL-1 locus or within the cyclin D1 gene was detected by CE or PFGE in any of the remaining 18 SLVL/LPL samples. Northern blot analysis showed expression of a normal-sized cyclin D1 transcript in the two SLVL/LPL cases with t(11;14)(q13;q32). In cases that lacked a cytogenetically demonstrable t(11;14) translocation, no cyclin D1 transcript was detected. Analysis of the BCL-1 locus was also performed in three other cases of B-cell disorders with t(11;14)(q13;q32) detected cytogenetically. Two cases were analyzed by Southern blot and showed rearrangement of the BCL-1 locus. Expression of high-level normal sized and/or truncated cyclin D1 transcript was also detected in these cases. These data show the importance of PFGE in the detection of rearrangements in the BCL-1 locus and show further the complexity of rearrangements in this locus. PMID- 8204892 TI - BCL2 translocations in leukemias of mature B cells. AB - Although translocations of the BCL2 gene are frequent in B-cell non-Hodgkin's lymphomas (B-NHL) the incidence, nature, and prognostic significance of similar translocations in the phenotypically related chronic leukemias of mature B cells are unknown. Therefore, we examined 170 cases of B-cell chronic lymphocytic leukemia (B-CLL), 7 cases of B-cell prolymphocytic leukemia (B-PLL), 25 cases of hairy cell leukemia (HCL) and 22 cases of splenic lymphoma with villous lymphocytes (SLVL) with defined cytogenetic abnormalities by DNA blot using both 5' and 3' BCL2 probes to search for rearrangement of the BCL2 locus. Translocation t(14;18) (q32.3;q21.3) was detected cytogenetically in 3 cases of B CLL. All had breakpoints in the 3' region of BCL2, mapping between the major breakpoint region (MBR) and the minor cluster region (mcr), the breakpoint clusters commonly detected in B-NHL. In 2 of the 3 cases, the breakpoint within BCL2 was mapped to a 1.0-kb EcoRI-HindIII fragment indicating a clustering of breakpoints. Two cases of B-CLL had cytogenetically detectable t(2;18)(p11;q21.3) or t(18;22)(q21.3;q11). Both had rearranged the 5' region of the BCL2 gene to the corresponding lg light-chain gene. Molecular cloning of the t(18;22)(q21.3;q11) showed that the translocation disrupted the BCL2 promoter region and the first untranslated BCL2 exon. Nevertheless, high levels of BCL2 protein were seen in this case. Only 2 other cases in whom cytogenetic analysis was not successful showed rearrangement of the 5' region of BCL2, an overall incidence of 2.3%. No cases of B-PLL, HCL, or SLVL showed either 5' or 3' BCL2 rearrangement. These data confirm the cytogenetic observations that translocations involving the BCL2 locus in all forms of leukemia of mature B cells are rare, and limited to a minor subset of B-CLL. BCL2 translocations in B-CLL involve hot spots of recombination of both the 5' and 3' regions of the BCL2 gene, which are distinct from those commonly seen in B-NHL, suggesting distinct pathogenic mechanisms. PMID- 8204893 TI - Rearrangement of CCND1 (BCL1/PRAD1) 3' untranslated region in mantle-cell lymphomas and t(11q13)-associated leukemias. AB - Rearrangement and overexpression of CCND1 (BCL1/PRAD1), a member of the cyclin G1 gene family, are consistent features of t(11q13)-bearing B-lymphoid tumors (particularly mantle-cell lymphoma [MCL]). Its deregulation is thought to perturb the G1-S transition of the cell cycle and thereby to contribute to tumor development. As suggested by previously published studies, rearrangement of the 3' untranslated region (3' UTR) of CCND1 may contribute to its activation in some lymphoid tumors. To define further the prevalence of such rearrangements, we report here the result of the molecular study of 34 MCL and six t(11q13) associated leukemias using a set of probes specific to the different parts of the CCND1 transcript. We also sequenced the entire cDNA of the overexpressed CCND1 transcripts in a t(11q13)-associated leukemia. DNA from four of these 40 patients showed rearrangement of the 3' UTR of CCND1 coexisting with major translocation cluster (MTC) rearrangement. Southern blot and sequence analyses showed that, as a result of these rearrangements, the 3' AU-rich region containing sequences involved in mRNA stability and in translational control is eliminated. Moreover, the finding that the CCND1 mRNA half-life was greater than 3 hours (normal tissues, 0.5 hours) in three t(11q13)-associated cell lines stresses the importance of posttranscriptional derangement in the activation of CCND1. Finally, we did not observe any mutation in the coding frame of the CCND1 cDNA analyzed. PMID- 8204894 TI - Giant actin inclusions in hematopoietic cells associated with transfusion dependent anemia and grey skin discoloration. AB - We evaluated a 13-month-old boy with cytoplasmic inclusions in hematopoietic cells, transfusion-dependent anemia, splenomegaly, and striking grey skin discoloration. Bright blue inclusions, 1 to 5 microns in diameter, were observed, primarily in the cytoplasm, of 30% to 40% of myeloid cells and in occasional monocytes, megakaryocytes, and lymphocytes on Wright Giemsa-stained bone marrow and blood smears. They occasionally involved the nucleus. The inclusions lacked lysosomes, polysaccharides, or lipids. Ultrastructurally, they lacked limiting membranes and consisted of tightly packed microfilaments averaging 7 nm in diameter, consistent with the size of actin monofilaments. On light microscopy, the inclusions stained with a monoclonal antibody to muscle-specific actin. Inclusion-positive cells contained increased F-actin content and were defective in chemotactic factor-activated actin polymerization; inclusion-negative cells polymerized actin normally. Neutrophil and platelet numbers and functional studies were mildly abnormal. Anemia and skin discoloration resolved spontaneously after 18 months, but the giant inclusions have persisted to the present. We conclude that this child has a previously unreported constellation of clinical and laboratory findings comprising severe anemia, intermittent neutropenia and thrombocytopenia, abnormal neutrophil migration and platelet aggregation, giant inclusions of actin in hematopoietic cells, and grey skin discoloration. PMID- 8204895 TI - Oxygen transport properties in malaria-infected rodents--a comparison between infected and noninfected erythrocytes. AB - This study was performed to investigate oxygen transport properties in whole blood (WB) of malaria-infected rats as well as in infected erythrocytes (IE) and noninfected erythrocytes (NIE) separated by density centrifugation. One week after inoculation with Plasmodium berghei, mean parasitemia was 26.5% and high correlations were found between parasitemia and hemoglobin concentration ([Hb]; r = -.902), mean cellular Hb concentration (MCHC; r = -.712), MetHb (r = .923), and base excess (r = -.922). Compared with control animals (C), the oxygen affinity was lower in WB under standard (pH 7.40) and simulated "in vivo" (pH 7.00) conditions (difference in P50, 5.7 and 5.1 mm Hg, respectively; 2P < .01, 2P < .05). In IE Hb and 2,3-biphosphoglycerate (2,3-BPG) concentrations were decreased (MCHC: IE 14.6 +/- 1.0, NIE 33.1 +/- 1.7 g/100 mL; [2,3-BPG]: IE 2.0 +/- 0.6, NIE 7.6 +/- 1.8 mmol/L), whereas [MetHb] and [ATP] were increased ([MetHb]: IE 19.0 +/- 3.7, NIE 0.7% +/- 0.8%; [ATP]: IE 33.5 +/- 2.4, NIE 6.2 +/- 1.0 mumol/g Hb). At pH 7.40, half-saturation oxygen tension (P50) was reduced in IE (29.6 +/- 2.6, NIE 39.2 +/- 5.4 mm Hg, 2P < .001), which correlates with lower [2,3-BPG], increased MetHb content, and higher intrinsic Hb-O2 affinity. However, at pH 7.00, the oxygen affinity was lower in IE when compared with NIE, which was most likely due to high [ATP] in IE. The resulting Bohr coefficients (BC) calculated for CO2 and lactic acid were extremely high in IE and low in NIE (at 50% O2 saturation BCCO2: IE -1.04 +/- 0.06, NIE -0.26 +/- 0.10, 2P < .001; BCLac: IE 0.82 +/- 0.16, NIE -0.47 +/- 0.07, 2P < .001), which was caused by different [2,3 BPG] and [ATP] as well as probably by structural changes of the Hb molecule. The O2 capacity was 14.1 mL per 100 mL erythrocytes in IE compared with 44.4 mL/100 mL in NIE. On the basis of the calculated arterio-venous O2 difference under "in vivo" conditions, the infected red blood cell fraction transports 30% of the O2 amount delivered to the tissues by the noninfected cells (IE 8.0, NIE 26.9 mL/100 mL red blood cells). We conclude that the O2 transport in malaria infected blood is not only affected by the degree of anemia but also by the percentage of infected erythrocytes. PMID- 8204896 TI - Chromosomal assignment of genes involved in glycosylphosphatidylinositol anchor biosynthesis: implications for the pathogenesis of paroxysmal nocturnal hemoglobinuria. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder that affects both sexes equally. The biochemical defect in PNH resides in the incomplete enzymatic assembly of glycosylphosphatidylinositol (GPI) anchors used for surface protein attachment. In all PNH patients tested to date, the biosynthetic defect occurs at the addition of N-acetyl-glucosamine to the phosphatidylinositol molecule (class A defect). A human cDNA, Piga, that repairs cell lines with the class A GPI-anchor biosynthetic defect has been recently cloned. Mapping of Piga to the X chromosome suggests that a single acquired mutation within Piga could alter GPI-anchor synthesis and result in PNH. However, this finding does not explain why all PNH patients have the class A defect. In the current study, the chromosomal assignment of Piga, as well as of Pigf and Pigh, two additional genes involved in GPI-anchor biosynthesis, has been established using a mouse interspecific backcross mapping technique. In contrast to Piga, both human and mouse Pigf and Pigh genes map to autosomes. The location of Pigf and Pigh suggests that mutations on both alleles of these autosomal genes would be necessary to produce PNH. This helps to explain the predominant class A defect in PNH. PMID- 8204897 TI - Myelodysplastic syndrome after autologous bone marrow transplantation: an additional late complication of curative cancer therapy. AB - Myelodysplastic syndrome (MDS) is a complication of conventional antineoplastic therapy but has rarely been reported after autologous bone marrow transplantation (ABMT). We reviewed records of 206 patients who underwent ABMT for lymphoma at the University of Minnesota (Minneapolis, MN) between 1974 and 1993. Of 206 patients who underwent ABMT for non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD), 9 patients developed an MDS or secondary acute leukemia between 5 and 60 months (median 34 months) post-BMT. Two patients had relapsed after transplant and received additional therapy before the diagnosis of MDS. They were censored from the statistical analysis, resulting in a cumulative incidence of 14.5% +/- 11.6% (95% confidence interval) at 5 years. Three patients (15.2% +/- 18.0%) had HD, and four (14.0% +/- 14.7%) had NHL. In vitro BM purging had no affect on the incidence of MDS, although patients receiving peripheral blood stem cells had a projected MDS incidence of 31% +/- 33% versus 10.5% +/- 12% if BM cells were used (p = .0035). The patients had received a median of 14 cycles (range, 6 to 40) of chemotherapy before autologous transplantation; Five of nine patients received radiation therapy before BMT conditioning, and all patients received radiation before the diagnosis of MDS. No BM cytogenetic abnormalities were evident pretransplant in three of three patients studied, and all nine had normal pretransplant BM morphology. All patients had morphologic BM findings typical of MDS, and six of six studied had clonal cytogenetic abnormalities. At the diagnosis of MDS, all nine patients were without clinical, radiographic, or autopsy evidence of recurrent lymphoma; Three of the nine patients have died from complications of cytopenias at 23, 36, and 45 months after transplant (3 to 10 months after the diagnosis of MDS), whereas 6 survive 8 to 63 months after transplantation (1 to 34 months post-MDS). These data emphasize the cumulative leukemogenic potential of standard and salvage radiation and chemotherapy regimens and highlight treatment-induced MDS as an important and frequent late complication of potentially curative BM transplant therapy. PMID- 8204898 TI - Detection of residual lymphoma cells by polymerase chain reaction in peripheral blood is significantly less predictive for relapse than detection in bone marrow. AB - Polymerase chain reaction (PCR) amplification of the t(14;18) has been shown to be a highly sensitive method to detect minimal residual disease in patients with non-Hodgkin's lymphoma (NHL) whose tumors bear this translocation. The ideal tissue source to detect residual lymphoma would be from a previously involved lymph node. However, lymphoid tissue is rarely available once patients achieve complete remission. Although PCR amplification has been used to detect residual lymphoma cells in both bone marrow (BM) and peripheral blood (PB) of patients in complete remission, it is presently unknown whether BM and PB are equivalent tissue sources to detect residual disease. In the present study, we compared the clinical utility of the detection of residual lymphoma in both the BM and the PB of patients with advanced-stage non-Hodgkin's lymphoma before, at the time of, and after high-dose therapy and autologous BM transplantation (ABMT). The detection of residual lymphoma in either the BM or PB was associated with decreased disease-free survival. However, in the present study, 44% of patients who relapsed had no evidence of circulating lymphoma cells in their PB. At the time of BM harvest, PCR-detectable residual lymphoma cells were detected in 211 of 212 patients; although, in a subset of these patients analyzed, lymphoma cells were detected in the peripheral blood of only 49% of patients. When residual lymphoma cells within the autologous BM are infused into the patient these cells are rapidly detectable circulating in the PB in the patient. These cells continue to circulate during the immediate posttransplant period and be detectable in the PB in the majority of patients who are infused with marrow containing residual lymphoma. We conclude that BM is a more informative tissue source than PB in detecting minimal residual disease at the time of and after ABMT, and that contamination of PB early after ABMT appears to be the consequence of reinfusion of lymphoma cells within autologous marrow. PMID- 8204899 TI - Inversions in the factor VIII gene in Spanish hemophilia A patients. PMID- 8204900 TI - CD39 as a novel marker of in vivo immune activation. PMID- 8204901 TI - Activation of factor X by factor VIIa on monocyte cell surfaces. PMID- 8204902 TI - Why are recently published platelet counts in normal mice so low? PMID- 8204903 TI - Frequent HLA class I and DP sequence mismatches in serologically (HLA-A, HLA-B, HLA-DR) and molecularly (HLA-DRB1, HLA-DQA1, HLA-DQB1) HLA-identical unrelated bone marrow transplant pairs. PMID- 8204904 TI - Structure and activity of Bombyx PBAN. AB - Two structurally related molecular species of pheromone biosynthesis activating neuropeptides (PBANs), PBAN-I and -II, were isolated from adult heads of the silkworm, Bombyx mori, and characterized. PBAN-I is a carboxyl-terminally amidated 33-residue peptide. Structure-activity relationship studies revealed that 1) its carboxyl-terminal pentapeptide is the smallest size showing activity, 2) the carboxyl-terminal amide is indispensable for activity, and 3) oxidation of three Met residues in PBAN-I to Met(O) (methionine sulfoxide) caused marked enhancement of activity, and the three Met(O) residues contribute equally to the enhancement of activity. Molecular design of PBAN analogs using a carboxyl terminal hexapeptide showed that modification of the amino-terminal amino group brought about a dramatic increase in activity. This increase was presumed to be mainly due to the increased stability in hemolymph. PBANs share the common carboxyl-terminal sequence, -Phe-Xaa-Pro-Arg-Leu-NH2, with myotropic peptides isolated from locust and cockroach. Examination of cross-activity of these two groups of peptides revealed that PBAN and its analogs exhibited myotropic activity comparable to myotropic peptides, while myotropic peptides showed extremely high pheromonotropic activity. In B. mori, PBAN activates sex pheromone (bombykol) production presumably by promoting the reduction reaction from acyl to alcohol, which is the last step in the biosynthesis of bombykol. PMID- 8204905 TI - Pheromonotropic and pheromonostatic activity in moths. AB - Pheromone biosynthesis in many species of moths requires a pheromonotropic neurosecretion, the pheromone biosynthesis activating neuropeptide (PBAN), from the brain-subesophageal ganglion-corpora cardiaca complex. Some investigations suggest that PBAN is released into the hemolymph and acts directly on sex pheromone glands (SPG) via a Ca++/calmodulin-dependent adenylate cyclase. Others suggest, however, that PBAN acts via octopamine that is released by nerves from the terminal abdominal ganglion innervating the SPG. These findings suggest that there are controversies on the mode of action of PBAN and other pheromonotropic factors, sometimes even within the same species. Mating in many insects results in temporary or permanent suppression of pheromone production and/or receptivity. Such a suppression may result from physical blockage of the gonopore or deposition of pheromonostatic factor(s) by the male during copulation that result in suppressed pheromone production and/or receptivity in females either directly or by a primer effect. In several species of insects, including moths, a pheromonostatic factor is transferred in the seminal fluid of males. Similar to the controversies associated with the pheromonotropic activity of PBAN, sometimes even within the same species, there appear to be controversies in pheromonostasis in heliothines as well. This paper reviews these conflicting findings and presents some data on pheromonostatic and pheromonotropic activity in Heliothis virescens that support and conflict with current information, raising further questions. Answers to some of the questions are partly available; however, they remain to be answered unequivocally. PMID- 8204906 TI - Patterns of biosynthesis and accumulation of hydrocarbons and contact sex pheromone in the female German cockroach, Blattella germanica. AB - De novo synthesis of contact female sex pheromone and hydrocarbons in Blattella germanica was examined using short in vivo incubations. Accumulation of pheromone on the epicuticular surface and the internal pheromone titer were related to age specific changes in hydrocarbon synthesis and accumulation in normal and allatectomized females. The incorporation of radiolabel from [1-14C]propionate into the cuticular methyl ketone pheromone fraction was positively related to corpora allata activity during two gonotrophic cycles. During peak pheromone production the total internal lipid fraction contained greater titers of pheromone than the cuticular surface, and it too exhibited a cycle internally, preceding the rise in external pheromone. This suggests that synthesis and accumulation of pheromone internally are followed by transport of pheromone to the epicuticular surface where it accumulates. Radiolabel was incorporated efficiently into both cuticular and internal hydrocarbons after the imaginal molt and until the peak of pheromone synthesis, but it declined to lower levels before ovulation and throughout pregnancy. The internal hydrocarbon titer decreased 58% after oviposition, suggesting deposition in the egg case. It remained relatively unchanged during pregnancy and increased again during the second gonotrophic cycle. In allatectomized females, hydrocarbon synthesis was reduced relative to control females until oviposition in the latter. However, subsequent rates of hydrocarbon synthesis in allatectomized females (without oothecae) exceeded the rates in sham-operated females (with oothecae). In the absence of ovarian uptake of hydrocarbons, the internal titer increased without the decline found in control females at oviposition. As internal hydrocarbons increased, so did cuticular hydrocarbons and both internal and cuticular methyl ketone pheromones. These patterns corresponded well with feeding patterns in sham-operated and allatectomized females, suggesting that pheromone production is normally regulated by stage-specific feeding-induced hydrocarbon synthesis (precursor accumulation internally) and juvenile hormone-induced conversion of hydrocarbon to pheromone. They also suggest that both the cuticle and the ovaries might be target sites for hydrocarbon and possibly methyl ketone deposition. PMID- 8204907 TI - Alternative splice form of type II procollagen mRNA (IIA) is predominant in skeletal precursors and non-cartilaginous tissues during early mouse development. AB - Type II collagen, generally considered to be characteristic of cartilage, has been localized in specific non-cartilaginous structures during embryogenesis and development of the skeleton. Type II procollagen is synthesized in two different forms generated by alternative splicing of exon 2 in the precursor mRNA transcript. One form (type IIA procollagen) contains a large cysteine-rich domain in the NH2-terminal propeptide, while the second form (type IIB procollagen) does not. These two forms are spatially expressed during development and chondrogenesis with the type IIB procollagen mRNA primarily expressed by chondrocytes while the IIA form is expressed in chondroprogenitor cells (Sandell et al. [1991] J. Cell Biol. 114:1307-1319). The present study demonstrates that the early non-cartilage expression, by somites, mesenchymal and epithelial cells, is predominantly the alternate splice form, type IIA procollagen mRNA. Later in development, the type IIB mRNA splice form is expressed by chondrocytes. During the development of intramembranous bones, such as the mandible, type IIA procollagen mRNA is also expressed. In this tissue, the splice form does not switch to type IIB mRNA and no cartilage is formed. These results show that expression of type IIA mRNA, whether by epithelial or mesenchymal cells, precedes formation of overt skeletal structures. PMID- 8204908 TI - Expression patterns of mRNAs for the gap junction proteins connexin43 and connexin42 suggest their involvement in chick limb morphogenesis and specification of the arterial vasculature. AB - Gap junctions which comprise a family of proteins called connexins have been implicated in the morphogenesis of the chick limb bud. We have examined the expression patterns of two members of the connexin family, connexin43 (Cx43) and connexin42 (Cx42), during the early development of the chick limb bud and embryo by in situ hybridization. Cx43 mRNA is expressed in high amounts in the apical ectodermal ridge (AER), which promotes the outgrowth of the mesodermal cells of the limb bud, and in the ectopic AER of the limb buds of polydactylous diplopodia 5 mutant embryos. In contrast, little Cx43 expression is detectable in nonridge limb ectoderm at early stages of limb development. These results suggest that Cx43 gap junctions may integrate the activity of the cells comprising the AER and compartmentalize them into a functionally distinct entity capable of directing limb outgrowth. In addition, Cx43 exhibits high expression in the posterior subridge mesoderm of the early limb bud that is growing out in response to the AER, but little expression in the anterior mesoderm. This graded distribution of Cx43 transcripts correlates with a functional gradient of gap junctional communication along the anteroposterior (AP) axis, and suggests that Cx43 gap junctions may be involved in pattern formation across the AP axis. At later stages of development, Cx43 is transiently expressed in high amounts in the precartilage condensations of the carpals and metacarpals, at a time when critical cell-cell interactions are occurring that trigger cartilage differentiation. In contrast, in the developing limb, Cx42 is expressed exclusively by the central artery. In the remainder of the chick embryo, Cx42 is expressed in high amounts by the vessels comprising the arterial vasculature, but is not expressed by the venous vasculature. Thus, Cx42 gap junctions may be involved in specification of the arterial vasculature of the limb and embryo. Cx42, but not Cx43, is expressed in the ventricle of the heart, and by cells along the intrasclerotomal fissure that separates the rostral and caudal halves of the sclerotome of somites into distinct communication compartments. PMID- 8204909 TI - Immunolocalization of S-crystallins in the developing squid (Loligo opalescens) lens. AB - S-crystallins are the predominant soluble proteins of the squid lens. Of these, S III crystallin is the major component and S-I and S-II crystallin are the minor lens components. The lens has a posterior and anterior segment, each derived from separate groups of ectodermal cells referred to as lentigenic cells. In the present study, the appearance of S-crystallins during the development of the lens of Loligo opalescens was followed by immuno-cytochemistry. S-crystallins of the lens and lentigenic cells were first observed at day 17 (Arnold stage 27) of embryogenesis. S-crystallins were not confined to a single region, but were present in the middle group (group 2) of lentigenic cells, the posterior lens primordium, and the processes connecting the lentigenic cells and the posterior lens primordium. Two days later (Arnold stage 28), the S-crystallins were also observed in the anterior group (group 1) of lentigenic cells, the anterior lens primordium, and the processes connecting the cells with the anterior lens primordium. Thus, during development, S-crystallins accumulate first in the posterior lens primordium and subsequently in the anterior lens primordium and their respective lentigenic cells and connecting lentigenic processes. Incubated sections of the adult lens and lentigenic cells also show specific immuno peroxidase staining when compared with controls. This evidence in combination with a recent investigation (West [1993] Ph.D. dissertation), which indicates that the cephalopod lens continues to grow throughout adulthood, suggests that squid lens crystallins are synthesized during adulthood. PMID- 8204910 TI - Prevention of spinal neural tube defects in the curly tail mouse mutant by a specific effect of retinoic acid. AB - Curly tail mouse mutant embryos (ct/ct) develop spinal neural tube defects (NTD) in 54% of cases, comprising isolated tail flexion defects and spinal bifida with tail flexion defects. Both types of spinal NTD result from delayed closure of the posterior neuropore (PNP). Previous studies (Seller et al. [1979] Proc. R. Soc. Lond. Biol. 206:95-107; Seller and Perkins [1982] Prenat. Diagn. 2:297-300) described a paradoxical effect of retinoic acid (RA) on the phenotypic expression of the ct mutation: Treatment with low doses of RA on day 8 of gestation increased the incidence of total NTD, whereas low doses of RA administered on day 9 resulted in reduced incidence of total NTD. In order to investigate further the reported preventive effect of RA, we have carried out detailed analyses of the effects of maternal treatment with 5 mg/kg RA on the incidence of NTD at different developmental stages, and on the development and growth of ct/ct embryos. We found that 5 mg/kg RA reduces the incidence of spinal NTD in a stage specific manner, without increasing the incidence of cranial NTD. The effect of RA is specific: There were no other alterations in morphogenesis, growth, development, resorption rate, or litter size. RA was more effective in the prevention of isolated tail flexion defects than of spina bifida. Prevention of isolated tail flexion defects was maximal (50% reduction) when RA was administered between 10 days 4 hours and 10 days 8 hours post coitum (p.c.) inclusive (24 to 34 somite stage).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8204911 TI - Dynamics of mitochondria in living cells: shape changes, dislocations, fusion, and fission of mitochondria. AB - Mitochondria are semi-autonomous organelles which are endowed with the ability to change their shape (e.g., by elongation, shortening, branching, buckling, swelling) and their location inside a living cell. In addition they may fuse or divide. These dynamics are discussed. Dislocation of mitochondria may result from their interaction with elements of the cytoskeleton, with microtubules in particular, and from processes intrinsic to the mitochondria themselves. Morphological criteria and differences in the fate of some mitochondria argue for the presence of more than one mitochondrial population in some animal cells. Whether these reflect genetic differences remains obscure. Emphasis is laid on the methods for visualizing mitochondria in cells and following their behaviour. Fluorescence methods provide unique possibilities because of their high resolving power and because some of the mitochondria-specific fluorochromes can be used to reveal the membrane potential. Fusion and fission often occur in short time intervals within the same group of mitochondria. At sites of fusion of two mitochondria material of the inner membrane, the matrix compartment seems to accumulate. The original arrangement of the fusion partners is maintained for some minutes. Fission is a dynamic event which, like fusion, in most cases observed in vertebrate cell cultures is not a straight forward process but rather requires several "trials" until the division finally occurs. Regarding fusion and fission hitherto unpublished phase contrast micrographs, and electron micrographs have been included. PMID- 8204912 TI - Molecular and cellular mechanisms of mitochondrial nuclear division and mitochondriokinesis. AB - Our present understanding of mitochondrial division can be summarized as follows: Mitochondria contain a specific genome, synthesize their own DNA, and multiply semi-autonomously. Strands of mitochondrial DNA (mt-DNA) in the in vivo organelles of all eukaryotes are organized to form mitochondrial nuclei (nucleoids) (mt-nuclei) with specific proteins including a histone-like protein and transcription factors at the central region of the mitochondrion. We can easily observe the mt-nucleus in vivo mitochondria in various organisms such as fungi, algae, plants, and animals by using high-resolution epifluorescence microscopy. Therefore, the process of mitochondrial division can be clearly separated into two main events: division of the mt-nuclei and mitochondriokinesis analogous to cytokinesis. Mitochondria undergo binary division which is accompanied by the division of the mt-nucleus. A remarkable characteristic of mitochondrial multiplication during the mitochondrial life cycle is that mitochondria can multiply the mt-chromosome by endoduplication until 50-100 copies are present. Mitochondria can then divide without mitochondrial DNA synthesis to eventually contain 1-5 copies of the mt-chromosome. This characteristic phenomenon can be observed during cell differentiation, such as during the formation of plasmodia and sclerotia of Physarum polycephalum and during embryogenesis and the formation of meristematic tissues in plants. The mitochondrial chromosome has a mitochondrial "kinetochore (centromere)" which is A-T rich and contains specific sequences such as topoisomerase binding sites, tandem repeats, and inverted repeats. A bridge of proteins may exist between the kinetochore DNA and membrane systems. Mitochondrial chromosomes can divide according to the growth of a membrane system between the kinetochores. Mitochondriokinesis progresses steadily along with mitochondrial nuclear division. As the membrane at the equatorial region of a mitochondrion contracts, the neck of the cleavage furrow narrows, and eventually the daughter mitochondria are separated. An actin-like protein may power mitochondriokinesis by separating the daughter mitochondria. In general, mitochondriokinesis occurs by contraction rather than by partition of the inner membrane. PMID- 8204913 TI - Interactions between brain mitochondria and cytoskeleton: evidence for specialized outer membrane domains involved in the association of cytoskeleton associated proteins to mitochondria in situ and in vitro. AB - The surface distribution of several proteins (porin, hexokinase, and two proteins associated with microtubules or actin filaments) on the outer membrane of brain mitochondria was analyzed by immunogold labelling of purified mitochondria in vitro. The results suggest the existence of specialized domains for the distribution of porin in the outer mitochondrial membrane. Similarities between the distribution of porin and the distribution of microtubule-associated proteins bound in vitro to mitochondria suggested that mitochondria and microtubules interact by binding microtubule-associated proteins to porin-containing domains of the outer membrane. This hypothesis was supported by biochemical studies on outer mitochondrial proteins involved in in vitro binding of cytoskeleton elements. In vitro interactions between mitochondria and microtubules or neurofilaments were analyzed by electron microscopy. These studies revealed cross bridging between the outer membrane of mitochondria and the two cytoskeleton elements. Cross-bridging was influenced by ATP hydrolysis and by several proteins associated with the surface of mitochondria or with microtubules. In addition, unidentified proteins which were recognized by antibodies to all intermediate filaments subunits were associated either with the mitochondrial surface or with microtubules. This data suggest the participation of additional cytoplasmic proteins in the interactions between cytoskeleton elements and mitochondria. PMID- 8204914 TI - Specimen preparation of free-standing, thick-metal, multilayered films in cross section. AB - A new preparation method permits the production of large-area, electron transparent, transmission electron microscopy (TEM) specimens in cross section of free-standing, thick, multilayered structures. Such production often has been difficult in the past because of large chemical differences between the component layers in the multilayer. This difference usually results in a large difference in thinning rates between the layers. A unique combination of electroplating, lapping, dimpling, and low-angle ion milling is a successful and reproducible technique for producing high-quality TEM specimens of these complex materials. Procedures and results presented here are for a 304 stainless-steel/copper multilayer having a repeat period of 20 nm and a total thickness of 20 microns. PMID- 8204915 TI - [Oncogenes and transcription factors. Recent advances]. PMID- 8204916 TI - [Study of the pelvic lymph nodes in urology]. AB - The lymph nodes of genito-urinary cancers are discussed and the topography of the pelvic lymph nodes is described. The various staging methods are described including imaging modality, examination by operative biopsy, showing the specificity, sensitivity and accuracy of these methods. According to the author, these two methods complement each other. PMID- 8204917 TI - [CSF-1 (colony stimulating factors 1) and CSF-1 receptor. General review and expression in invasive breast tumors]. AB - CSF-1 (colony stimulating factor-1), initially considered to be a monocyte specific growth and differentiation factor [4], has recently been shown to be produced in human endometrium [16], placenta [7], as well as in numerous solid tumors [19-23, 26, 27]. The CSF-1 receptor (a protein product of c-fms) [24] is a member of the tyrosine kinase receptor family and an autocrine or paracrine mechanism of activation has been suggested. Overactivation of this receptor can lead to a malignant phenotype in various cell systems [20, 21]. We review the biology of CSF-1 and fms expression in normal as well as in malignant tissues with particular reference to a potential role for CSF-1 in breast tumour invasion. PMID- 8204918 TI - [Hodgkin disease, clinical stages IA-IIB: evaluation of the value of cisplatin. Preliminary results]. AB - Cisplatinum is highly effective in numerous solid tumors and was evaluated in Hodgkin's disease clinical stages (CS) I/II. Sixty-five patients (43 male, 22 female; median age 25, with 12 patients under 16: CS IA-IIA 41, IB 5, IIB 19) were randomly assigned to one of the following arms (PAF87 protocol): 3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine with methylprednisolone) cycles (ABVD arm) or 3 ABVD plus cisplatinum cycles (ABVD-Plt arm) followed by radiotherapy (RT); extended field (40 Gy) RT with a short paraaortic field including the spleen (30 Gy) was then administered in the ABVD arm; extended field (30 Gy) without lombosplenic port prophylaxis. RT was administered in ABVD Plt arm when patients were in complete remission (CR) after chemotherapy (CT). Median follow-up was 35 months (6-62 months). During CT, 1 patient (ABVD-Plt) died from viral meningo-encephalitis; five patients (1 ABVD, 4 ABVD-Plt) stopped treatment because of emesis, of whom three receiving only 1.5-2.5 (ABVD-Plt) cycles, are still in CR after 13-60 months. Fifty-five patients (27 ABVD-Plt) were in CR after CT. Among the 27 ABVD-Plt patients, all in CR after RT, two died (one from myocardial infarction and one from immunoblastic lymphoma); one patient from the ABVD arm died from gastro-intestinal hemorrhage in 1st CR. No ABVD-Plt patient relapsed; 1 ABVD patient relapsed in non-irradiated area. At five years, actuarial survival/relapse-free survival was 96.1/90% and 88.2/100% for ABVD and ABVD-Plt patients, respectively. PMID- 8204919 TI - [Quantitative binding of cysteine-proteinases to a basement membrane: role in their digestion during tumor invasion]. AB - Binding of cysteine-proteinases of the papain-superfamily (papain and cathepsins B, B-like and L) to basement membranes was studied by using the enzymatic activity of these proteinases against their specific fluorogenic substrates. The basement membrane used for these experiments is the bovine lens capsule (weight approximately 50 mg). Papain inactivated by E64 was used in competition experiments, that made it possible to obtain the equilibrium constant, Kd and the number of substrate sites per capsule, n. Values were found around 10(-7) M for Kd, and in the 10(12) range for n. Such results would be of significant interest for the understanding of the biological role of cysteine-proteinases in tumour invasion and other types of tissue remodeling. PMID- 8204920 TI - Putative role of antioxidant enzymes and glyoxalases in carcinogenesis. AB - The effects various drugs exert on antioxidant enzyme and glyoxalase activity in rat livers were studied. All drugs tested provoked a marked reduction in glutathione peroxidase and a small drop in both glyoxalase I and II activity. It is hypothesized that the substances tested support tumour development by neutralizing organic peroxides, thereby favouring the oxidation of carcinogens and, as a consequence, the formation of metabolites that trigger neoplastic transformation. The reduction in glyoxalase activity is probably attributable to the enhanced cell proliferation induced by the treatment. PMID- 8204921 TI - [Thrombosis and cancer]. AB - Thrombotic episodes represent the second cause of mortality in cancer patients. These complications are more frequent with some adenocarcinomas and hematologic malignancies. The mechanisms of pathogenesis are complex inducing an unbalanced function of the antithrombotic system. According to the type of tumor and the underlying mechanism, clinical manifestations are generally severe. The diagnosis of these thromboses are essentially clinical or radiological. The treatment is based on heparinotherapy, thrombolytic agents or eventually on surgery, which is not discussed here. PMID- 8204922 TI - Circulating immune profile in patients with pre-cancer and cancer of the cervix: a cross sectional study among Indian women. AB - To fully understand immune competence in subjects with precancerous and cancerous lesions of the uterine cervix, various markers of T and B cells in peripheral blood were evaluated. The cellular measures were the absolute numbers of CD2, CD3, CD22, CD25, CD4, CD8 and CD4/CD8 T cell ratio and serologic measures were the levels of cellular products ie interleukin-2 (IL-2) and soluble interleukin-2 receptors (SIL2-R). Eighty-five subjects were analysed, and diagnosed histologically as CIN (n = 33) and invasive cancer (n = 22). Thirty women with normal Pap test results served as controls. Results on cellular markers showed a significant decrease in peripheral blood lymphocyte counts in patients with higher grades of cervical lesions as compared to controls (CIN III P < 0.05 and invasive cancer P < 0.001). Similar trends were observed for CD22 cell counts (P < 0.001). A consistent decrease was observed for CD2 positive T lymphocytes in patients with higher grade cervical lesions only. In addition, a decrease in CD4 T cells with a relative increase in CD8 and CD25 cell count was observed in these groups of patients, leading to a considerable reduction in CD4/CD8 T-cell ratio. Results obtained on soluble cellular products revealed that serum levels of IL-2 and SIL2-R in patient groups were significantly higher than controls (P < 0.001). Preliminary findings indicated a host-vested cellular impairment, evidenced by immune deficit and immune-stimulation, in women with pre-cancer and cancerous lesions of the cervix. PMID- 8204923 TI - [Hereditary predisposition for cancer of the breast and the ovary]. AB - Familial breast cancers represent about 10% of all cases of breast cancers. A predisposition locus has been located in the 17q21 chromosomal region. Nineteen French breast and breast-ovarian cancer families were tested for linkage with five highly polymorphic 17q markers. The five breast-ovarian cancer families as a group give positive evidence for linkage, whereas the 14 breast cancer families do not. Heterogeneity of linkage of familial breast cancer is significant in France and supports the existence of more than one susceptibility gene. PMID- 8204924 TI - [Huriet's law in cancerology. 10th Meeting of the Association of Psychology and Cancer. Nancy, France, 3-4 December 1992]. PMID- 8204925 TI - [Huriet's law in cancerology. Informed consent in current French legislation]. PMID- 8204926 TI - [Huriet's law in cancerology. Public opinion on informed consent]. PMID- 8204927 TI - [Huriet's law in pediatric cancerology]. PMID- 8204928 TI - [Huriet's law in cancerology. Ethical commissions and medical research in Switzerland]. PMID- 8204929 TI - [Huriet's law in cancerology. Ethical debate about informed consent of the patient]. PMID- 8204930 TI - [Huriet's law in cancerology. Psychological and relationship problems from the oncologist's point of view]. PMID- 8204931 TI - [Huriet's law in cancerology. Psychological consequences of Huriet's law in oncologic units]. PMID- 8204932 TI - [Huriet's law in cancerology. Reflexions on physician-patient relations and informed consent in thoracic oncology]. PMID- 8204934 TI - [Apropos of A. Lortholary's review: "Paraneoplastic syndromes (I)"]. PMID- 8204933 TI - [Evaluation of consequences of written informed consent on physician-patient relations. Apropos of Huriet's law]. PMID- 8204935 TI - [Molecular definition of carcinogenetic risk]. PMID- 8204936 TI - [Reality and hope: a critical approach to an antiemetic drug]. PMID- 8204937 TI - [Role of ondansetron in oncology]. AB - The aim of this paper is to compare ondansetron to other antiemetic products used in cancerology. Twenty randomised trials studying ondansetron, and published in international reviews, were analyzed and synthesized. The conclusion is that ondansetron is of demonstrated short term efficiency. It seems to be slightly more efficient than metoclopramide, and its association with dexamethasone increases its efficiency. Doses of 8 mg or 24 mg do not differ from doses of 32 mg, and bolus administration from infusion administration. There are no data on the duration of the protection after the first course of chemotherapy. PMID- 8204938 TI - [Malignant melanoma of the uvea]. AB - Intraocular melanoma is the most common primary ocular malignancy in Whites. Epidemiologic studies demonstrated the role of sun exposure as a risk for uveal melanoma. Conservative treatment techniques are indicated for localised tumors when feasible. External radiation therapy and radioactive eye plaque brachytherapy seem as effective as surgery in term of survival. High tumor doses can be safely administered with either helium or proton beams. A partial preservation of the vision is possible in most of patients. However, even for locally controlled patients, distant metastases can occur. Liver is the most frequent metastatic site, and also the first involved. Liver metastases are associated with a low response rate, to dacarbazine and nitrosourea. Recent studies using a new nitrosourea, fotemustine, administered locally through an intra-arterial catheter, show that it produces encouraging results with a good hepatic and hematologic tolerance. PMID- 8204939 TI - [Cancer immunotherapy: immunologic bases, reality and hopes]. AB - The use of the immune system for the treatment of cancer is still debated. Recent advances in antigen presentation and recognition mechanisms, and the characterization of tumor-specific antigens generating a T cell response are crucial steps for the stimulation of research in this direction. These advances should allow the development of selective immunotherapy, either passive (infusion of lymphocytes with specific recognition of autologous tumor) or active (vaccination), and the evaluation of this new approach in cancer treatment strategies. PMID- 8204940 TI - [Treatment with cytokines of metastatic kidney cancer: the Lyon experience]. AB - Between October 1987 and June 1992, 244 patients with metastatic renal carcinoma were referred to our Institute. One hundred and sixty-nine were included in immunotherapy protocols. The 40 most recent patients were included in the ongoing multicentric randomised Crecy study. The previous patients were treated with IL2 as a continuous infusion or high doses intravenous IL2 combined with alpha interferon (IFN) or a combination of IL2 and IFN as subcutaneous low doses. Some patients received as rescue treatment a combination of IL2 with Tumor Necrosis Factor (TNF). First line immunotherapy with cytokines gave 14-25% response rates in these patients with 5-10% of complete persistent remissions. The most intensive regimen was responsible for the most severe toxicity as well as the highest response rate. TNF does not appear to be of great concern since its systemic administration induced important limiting toxicities. This work emphasizes the need for prospective studies in order to evaluate the optimal mode and schedule of treatment as well as to investigate the impact of immunotherapy on survival. PMID- 8204941 TI - [A prospective study of alveolar bone resorption after radiotherapy and chemotherapy]. AB - A prospective comparative study of the alveolar bone resorption after teeth extraction was achieved in a series of 79 patients in order to analyze macroscopically the possible consequences of radiotherapy and chemotherapy on the toothless edges. After quarterly coronal and sagittal X-rays for two years, this study enhances quite a similar vertical resorption for the radiation and chemotherapy-treated patients as well as for the witness patients. The alveolar bone resorption progression also appears unaltered by anti cancerous treatments. In both cases, a resorption stabilisation can be clearly seen after 6 months according to dental extractions. The vertical alveolar bone resorption is more important in incisor and canine regions. The anti cancerous treatments may not have significant disastrous consequences as far as available bone amount is concerned, on a post prosthetic restoration. PMID- 8204942 TI - [Antiemetic effect of ondansetron in recurrent chemotherapy with cisplatin]. AB - Six hundred and twenty-eight courses of cisplatin containing chemotherapy were recorded in patients receiving up to three courses of cytotoxic drugs with ondansetron (OND) given as an antiemetic agent (32 mg as a single iv dose or as a continuous infusion). The sample size of patients decreases from one course to another due to phenomena which may or may not be related to the chemotherapy and the anti-emetic treatment or to the evolution of the cancer disease. For patients with incomplete response to ondansetron, withdrawals could be related to an insufficient antiemetic effect as is known with other antiemetic drugs. Conversely, it is not the case for patients who had a complete response. Therefore, to avoid any bias due to patient selection, the analysis is based on the probability of changes from complete to incomplete response or from complete to complete response between two subsequent courses (i and i + 1). The response to OND treatment for the course i + 1 depends not only on the efficacy during this course (i + 1) but also on the response during the prior course (i). A discrete time-dependent statistical model (Markov chain) was used to test the evolution of the probability of remaining in complete response. This probability was equal to 66% between the first and the second course, and to 88% between the second and the third one. The probability of remaining in complete response significantly increased during repeated courses (P = 0.001). These results show that in patients for whom OND treatment allows a complete antiemetic control during the first course of chemotherapy, the probability of remaining with no emetic episodes at all increases during the two subsequent courses. PMID- 8204943 TI - [Treatment of advanced breast cancer in postmenopausal women with droloxifene: results of a double-blind phase II trial for dose determination]. AB - To determine the optimal daily dose of a new antiestrogen, droloxifene, for the treatment of advanced breast cancer, we have conducted a multicenter, randomized, double blind trial. Postmenopausal women with advanced breast cancer, who could not benefit from loco regional therapy, with positive or unknown estrogen or progesterone receptors were entered in this study. Droloxifene was administered in a double blind randomized design, with daily dose of either 20 (group I), 40 (group II) or 100 mg (group III). None of the patients had received previous systemic antitumor therapy, with the exception of adjuvant chemotherapy terminated at least one year before the patient's recruitment. Patients with at least one measurable tumoral lesion were entered into the trial. Three hundred and sixty nine patients have been enrolled, 234 are fully evaluable for efficacy. Objective response rate (CR + PR) is 31.1, 44.6 and 41.9% for the groups I, II and III respectively (P = NS). Time to response has been short: in the three groups, 50% of the responses have been observed within the 2 first months of treatment. Time to disease progression is 6, 8.3 and 6 months respectively for the 20, 40 and 100 mg/day treatment group. Side effects have been moderate and not dose related. Hot flushes and gastro intestinal disorders have been observed most often. This promising new drug deserves further study and randomized comparison versus tamoxifen. PMID- 8204944 TI - [Is there a place for 2nd look laparotomy in the treatment of ovarian cancers?]. AB - The charts of 147 patients with advanced ovarian cancers responding completely (CR) or partially (PR > 50%) to a primary cisplatin-based chemotherapy are reviewed. All fulfilled our criterias to undergo second-look laparotomy. One hundred patients (group A) underwent second-look laparotomy and 47 patients (group B) other features of control: laparoscopy 37 patients, clinical control ten patients. Apart metastatic spread more frequent in group B (A vs B = 10 vs 32%) and tumor grade 1 more frequent in group B (A vs B = 33 vs 49%), the two groups were well balanced concerning tumor characteristics and treatment features. All patients had received a complementary treatment after the second look procedures. With a median follow-up of 86 months in group A and 104 months in group B, no difference was found in overall nor in recurrence-free survival. Within group A, 34 patients had achieved pathologic proved complete remission. Their 5-year survival was 73% with an incidence of recurrence of 32%. Second-look laparotomy was found an invasive technique with a 15% operative morbidity. Its therapeutic apport seems absent and the diagnostic role limited to indication of radiotherapy in CR patients. Second-look laparotomies should be reserved to trials evaluating its proper place but should not be used systematically to assess tumor response to chemotherapy. The good 5-year survival of the CR mi group suggest the beneficial impact of complementary treatment, but prospective trials are needed to evaluate the place of this treatment. PMID- 8204945 TI - [Prognostic value of a continuous variable and an optimal cutoff point]. AB - To study the prognostic value of a continuous variable, cathepsin D in breast cancer, for example, it has been suggested to consider all the divisions of the population in two groups obtained by changing the cutoff level for cathepsin D, and to select the division leading to the largest difference in survival between the two groups. This method, called optimized cutoff point is statistically incorrect as currently used, and requires corrections. Moreover, the optimised cutoff point will be different in different groups of patients, and has no interpretation either biologically or statistically. Continuous prognostic factors should be studied by dividing the population in more than two groups, in order to examine the shape of the relation between the factor and survival. The limits used to define the groups should not depend on the observed survival in the groups. PMID- 8204946 TI - [Effects of LAK cells activated by IL-2 on MCF-7 human breast cancer cell line maintained in organotypic culture]. AB - Lymphokine Activated Killer (LAK) cells, stimulated by interleukin 2 (IL-2) have a pronounced antitumor effect in the therapy of melanoma and renal cancers. LAK cells were cultivated in presence of the nodules of the human breast adenocarcinoma cell line MCF-7 maintained in organotypic culture to study the interactions between lymphocytes and breast tumor cells. After two days of co culture, the proliferation of MCF-7 nodules and that of LAK cells was diminished about five folds. The cytotoxic effect of the latter, appreciated by Chrome 51 release was unchanged after the coculture. In histological sections, the penetration of the LAK cells into the MCF-7 nodules was accompanied by an increase of tumor necrosis but also by a glandular differentiation of cancerous tissue. Polarized epithelial cell formations bording neoplasic lumens with intracytoplasmic vacuoles filled with mucus, appeared in the nodules. The immunohistochemistry underlines the presence of T lymphocytes marked by UCHL1 and CD3 antibodies and of Natural Killer (NK) cells marked by IOT10, located between the MCF-7 cancer cells. In electron microscopy, the membrane contacts were tight and were accompanied by the appearance of secondary lysosomes and nuclear alterations. The relatively low infiltration level of the nodules may lead to the supposition that an indirect mechanism will intervene in this dual action of a LAK cells: increase of necrosis, although partially, and development of glandular and functional differentiation. PMID- 8204947 TI - Failure of monoclonal antibodies against tumor associated antigens to improve tumor targeting of LAK cells in a model of rat colon carcinoma. AB - The possibility of targeting LAK cells to the tumor by arming them with monoclonal antibodies directed against tumor associated antigens was tested in a rat model of colon carcinoma. Peritoneal carcinomatosis was generated by injection of cloned tumor cells and 111In-labeled LAK cells were injected in the tail vein after preincubation with the monoclonal antibodies themselves. It appeared that the antibodies did not significantly improve tumor targeting of LAK cells, most of the radioactivity being recovered in the spleen, the liver, the kidney or the lung, and only a small fraction in the tumor. PMID- 8204948 TI - [Deep venous thrombosis on implantable infusion devices. A prospective study of 72 patients with Doppler ultrasonography of veins of the neck (jugular, subclavian and brachiocephalic trunk)]. AB - Seventy-two consecutive patients with totally implanted catheters for administration of chemotherapy for solid tumours or lymphomas were studied prospectively to assess the prevalence of venous thrombosis. During the follow-up period of 343 (6-1,177) days, 11 cases of venous thrombosis (15.2%), of which 45% were partial and only 36% symptomatic were observed. Venous thrombosis was an early complication, 6/11 cases being observed within 1 month of implantation. No clinical or biological predisposing factor, apart from the presence of malignant disease, could be identified. Doppler ultrasonography is a good method of following-up these patients. This method should become an essential diagnostic tool in this field. PMID- 8204949 TI - [RB and P53 tumor suppressor genes]. PMID- 8204950 TI - [P53 genes and solid tumors]. AB - The p53 gene is known to play a central role in cancer. In fact, no human tumor type is devoid of p53 mutations, although differences can be seen in the relative frequencies and patterns of nucleotide substitutions. Our work illustrates these differences, since frequencies of mutations ranged from 15 to 80% and the patterns of mutations were distinctly different in skin cancers compared to breast tumors. Furthermore, it is well established that whenever p53 mutations occur during tumor progression, their appearance greatly affects the natural evolution of cancer. This is confirmed by the correlations found between p53 mutations and the negative outcome of the disease in a number of tumor types. PMID- 8204951 TI - [P53 genes and malignant hematologic diseases]. AB - Mutations of the P53 tumor suppressor gene represent the most common genetic lesion in human solid tumors. In hematological malignancies, P53 alterations are detected in the evolution of the chronic myelogenous leukemia to myeloid blast crisis. P53 mutations were also found to be associated with Burkitt's lymphoma and HTLV-1 related adult T-cell leukemia. These results support the notion that alterations of the P53 gene may be involved in the progression of these hematological diseases. PMID- 8204952 TI - [The retinoblastoma gene: will therapeutic use of its tumor suppressive properties be possible?]. AB - The retinoblastoma is a rare childhood tumor which occurs in children, 40% of them being diagnosed in an hereditary context. The gene involved in the hereditary predisposition and in the tumoral development was isolated (RB-1) and is of the antioncogene-type. RB-1 mutations were found in many other tumors. The absence of the antioncogene protein expression is responsible for the tumor development and a contrario its presence in normal cells has tumor suppressive properties. This property was demonstrated by phenotype reversion of retinoblastoma or other cell lines (with no RB-1 protein), induced by reintroduction of the gene coding for the normal RB-1 protein. The normal RB-1 protein undergoes multiple phosphorylations during the cell cycle, regulating its activity, the active form being hypophosphorylated. RB-1 is involved in the transcription regulation of many cell cycle genes, and in cell differentiation. Experimental animal models are under investigation, in order to established whether RB-1 overexpression in normal cells will protect them from tumor development, and to plan tumor gene therapy by injection of recombinant viruses allowing RB-1 expression in tumor cells. PMID- 8204953 TI - [Search for tumor suppressor genes: chromosome deletions and loss of heterozygote property in human tumors]. AB - The tumor suppressor genes presently individualized are still few. A step in their identification is the search for chromosomal deletions and loss of heterozygosity. These studies are summarized. PMID- 8204954 TI - [Nucleoside diphosphate kinase/Nm23 and metastatic potency]. AB - The nm23-H1 gene encoding the nucleoside diphosphate (NDP) kinase A has been proposed as a tumor metastasis suppressor. Two important features emerge from published data: 1) an inverse correlation between the metastatic invasion and the level of NDP kinase/Nm23 was observed in melanomas, hepatocellular carcinomas and, in some studies, on breast carcinomas; 2) an overexpression of NDP kinase/Nm23 was observed in several solid tumors as compared to normal surrounding tissues, positively correlated with aggressiveness in the case of neuroblastomas. The level of NDP kinase/Nm23 in tumors appears to be altered in different ways, related or not to the metastatic potential, depending on the tissue of origin. Its evaluation as a prognostic or diagnostic marker of tumor invasion and aggressiveness deserves further study. PMID- 8204955 TI - [Are rap genes anti-oncogenes?]. AB - The products of the ras-related rap genes (rap1 and rap2) are small G-proteins that share a high degree of structural (around 50% of identical amino acids) and functional homology with the products of ras oncogenes. In particular, the sequence of the effector domain of ras and rap proteins is identical, which has prompted speculations that they might compete for interaction with a common effector. In effect, by attempting to identify genes whose expression would be capable of reverting the phenotype of ras-transformed cells, the laboratory of Makoto Noda isolated the Krev-1 gene that was found to encode the same protein as the rap1A gene. Biochemical studies have since shown that the rap1 protein effectively competes with ras proteins for their interaction with the p120-GAP protein, a potential effector of the biological activity of ras proteins that strongly stimulates their GTPase activity; however, p120-GAP does not stimulate the GTPase activity of the rap1 protein. In contrast, the rap2 protein has no effect on the interaction between ras proteins and p120-GAP. Similarly, whereas overexpression of the rap1 protein is able to antagonize the transforming potential of oncogenic ras proteins, a considerable overexpression of normal or mutated rap2 proteins has no effect on cellular proliferation or transformation induced by ras oncogenes. It is therefore concluded that rap genes cannot be considered as anti-oncogenes; whether the physiological function of the rap1 protein is to modulate the activity of ras proteins, or its antagonistic effect is merely attributable to its experimental overexpression remains to be established. PMID- 8204956 TI - [The C-Jun oncoprotein]. AB - Jun and Fos are major components of the transcriptional complex AP-1 (Activator Protein-1), a collection of dimeric transcriptional activators composed of members of the Jun and Fos family of bZIP proteins, that bind to a common site known as TRE (TPA Responsive Element) or the AP-1 site. Transcription of c-jun is rapidly induced by exposure to different extra-cellular signals like growth factors, cytokines, tumor promoters (TPA), UV and other DNA-damaging agents. Transcriptional activation of c-jun is a two step mechanism. First, the pre existing c-Jun protein is activated by posttranscriptional modifications, and second, modified c-Jun activates its own transcription, and the expression of AP 1-dependent genes. Modifications of c-Jun include dephosphorylations, phosphorylations and oxydo-reduction. The transcriptional activation by c-Jun is modulated by heterodimerization with other members of the bZIP family of proteins, and by transcriptional interference with other transcription factors like some members of the hormone nuclear receptors, or MyoD. AP-1 is tightly associated to both the control of cell proliferation and the oncogenic process. Constitutive activation of AP-1 leads to cell transformation in vitro, probably due to the accumulation of homodimeric c-Jun:c-Jun complexes. This hypothesis has been directly confirmed by constructing c-Jun hybrid proteins capable to form only homodimers. Deregulated expression of such proteins efficiently transforms primary cells in culture. These hybrid proteins constitute a powerful tool in order to identify new cellular functions AP-1-dependent, involved in the control of cell proliferation. PMID- 8204957 TI - [Demonstration of transcriptional regulation of protein kinase C by class II anti HLA antibodies in human CA cells of the lymphoblastoid line]. AB - HLA class II antigens are involved in signal transduction in B lymphocytes. We have previously reported that the ligation of HLA class II antigens in B cells results in an increase of cytosolic and membrane PKC activity [3]. Unlike TPA, no translocation of the cytosolic PKC was observed following anti HLA class II antibody treatment. However, an increase of both PKC activity (cytosolic and membrane) and quantity was observed. These effects are completely abolished by actinomycin D treatment. Northern blot analysis and PCR reaction revealed that anti HLA class II antibodies induce an increase of the PKC beta level which is significant after 20 minutes of stimulation and rose to a maximum after 60 minutes. Taken together, our results show that anti HLA class II antibodies exert a transcriptional regulation of PKC in human B lymphocytes. PMID- 8204958 TI - [Radiation-induced cutaneo-muscular fibrosis (III): major therapeutic efficacy of liposomal Cu/Zn superoxide dismutase]. AB - Sub-cutaneous and muscular fibrosis are common and irreversible late effect of radiation on normal tissues. An experiment was designed to test the effectiveness of superoxide dismutase in reducing late radiation injury. This study was performed in an experimental porcine model of acute localized gamma irradiation simulating human accidental overexposure: 12 Large White pigs were irradiated on the thigh with a collimated gamma 192Ir source, so that the dose was 160 Gy/skin (100%) and 40 Gy/2 cm depth (25%). In this model, fibrosis appears in 4 to 5 months. The heterogeneous sclerotic tissue is composed of stable fibrotic areas poorly cellularized and active areas with a high density of myofibroblasts and inflammatory perifibrotic part. Lipsod administration modalities were six intramuscular injections during 3 weeks (twice weekly) either 10 mg/inj (five pigs) or of 100 mg/inj (five pigs). A methodic evaluation by two examiners consisted of measurements being taken before and after treatment: sum of the two largest perpendicular measurable dimensions, cutaneous projected surface of palpated fibrotic block, ultrasound fibrosis deepness and extrapolated volume. We conclude that Lipsod is the first drug ever described that reduces radiation induced fibrosis. Its efficacy in this model was highly significant, with a regression higher than 40% in size and 70% in surface and volume, 12 weeks after the end of treatment. This response was rapid, reproducible without dose-effect or toxicity in the limits studied. This work confirms previously published results in humans. PMID- 8204959 TI - [Maffucci syndrome and ovarian tumor]. AB - Maffucci's syndrome was first described in 1881 and results of a mesodermic dysembryoplasia, congenital but not hereditary. Pathogenic hypothesis are multiple. This syndrome is characterized by the occurrence of multiple haemangiomas in the soft tissue, and multiple enchondromas of the bones. The association of ovary tumor is however exceptional. Four cases are reported in the literature; we report the fifth case. PMID- 8204960 TI - Acute eosinophilic pneumonia evaluated with high-resolution computed tomography. AB - We describe two cases of acute eosinophilic pneumonia (AEP) presenting with high fever and hypoxia of acute onset with bilateral interstitial infiltrates on chest roentgenograms. Diagnosis was confirmed in each case by bronchoalveolar lavage and transbronchial lung biopsy in which the pathologic process was limited to the lung interstitium. High-resolution computed tomography (HRCT) of the thorax at the height of the disease process revealed peripheral ground-glass opacities along the bronchovascular bundles. Symptoms and radiologic abnormalities resolved spontaneously within two weeks. The HRCT-findings may reflect the pathologic process in AEP and the ground-glass opacities likely indicate spontaneous resolution without corticosteroid therapy. PMID- 8204961 TI - Fibromyxoma of the trachea. AB - A 53-year-old male with a small cell carcinoma of the lung was admitted to the Department of Respiratory Diseases, Nikko Memorial Hospital. During bronchofiberoptic examination of the cancer, a small nodule was discovered on the anterior wall of the trachea, about 8 cm below the vocal cord. Histopathologically, it was diagnosed as fibromyxoma of the trachea. Primary tumors of the trachea are very rare and fibromyxoma of the trachea is extremely rare. This is only the second report of a fibromyxoma on the tracheal wall. In this report its clinical manifestations were compared with those reported in the first case. PMID- 8204962 TI - IGF-II producing hepatic fibrosarcoma associated with hypoglycemia. AB - A 67-year-old male was admitted with the complaint of weakness at hunger early in the morning, when blood glucose was less than 40 mg/dl. The abdominal ultrasonogram and computerized tomogram demonstrated a huge tumor in the right liver lobe. Hypoglycemia disappeared after transcatheter arterial embolization. Then hepatic lobectomy was performed. The tumor was histologically shown to be a fibrosarcoma. Insulin-like growth factor-II was intensely stained in the Golgi area of the tumor cells, suggesting its role in the mechanism of hypoglycemia. PMID- 8204963 TI - Still's disease relapse with severe pneumonitis after prolonged remission. AB - A 20-year-old woman who had suffered from Still's disease was admitted for fever and progressive pneumonitis after long-term remission. High spiking fever, leukocytosis, splenomegaly and an extremely high serum ferritin concentration strongly suggested a relapse of Still's disease. Intensive therapy with high-dose methylprednisolone, cyclophosphamide and gamma globulin was required for the severe pneumonitis, which was thought to be a rare manifestation in Still's disease. PMID- 8204964 TI - Immune mechanism of digestive organ. PMID- 8204965 TI - The immunological aspects of chronic gastritis. PMID- 8204966 TI - Inflammatory bowel disease and immunology. PMID- 8204967 TI - Autoimmune hepatitis. PMID- 8204968 TI - Classification of amyloid and amyloidosis. PMID- 8204969 TI - AA amyloidosis and AL amyloidosis. PMID- 8204970 TI - Transthyretin and familial amyloidotic polyneuropathy. PMID- 8204971 TI - Amyloid beta/A4 peptide associated with Alzheimer's disease and cerebral amyloid angiopathy. PMID- 8204972 TI - New type of amyloidosis. a). beta 2-Microglobulin and hemodialysis. PMID- 8204973 TI - New type of amyloidosis. b). Islet amyloid polypeptide (IAPP/amylin) in non insulin-dependent diabetes mellitus. PMID- 8204974 TI - Infection in severe hematologic disorders with special reference to its changing patterns. PMID- 8204975 TI - Pulmonary mycosis. PMID- 8204976 TI - Current topics of chlamydial respiratory tract infections--special reference to the epidemiology and clinical findings of Chlamydia pneumoniae infections in Japan. PMID- 8204977 TI - Transfiguration of rickettsial diseases: tsutsugamushi disease and spotted fever group rickettsiosis in Japan. PMID- 8204978 TI - Mutations of hepatitis B virus correlate with liver disease. PMID- 8204979 TI - Replicative level of hepatitis C virus (HCV) in chronic hepatitis C. PMID- 8204980 TI - Chronic EB virus infection and cytokine: IL-2, interferon gamma, and BCRF1 gene product (viral IL-10). PMID- 8204981 TI - Linear algebraic transformations of the bidomain equations: implications for numerical methods. AB - A mathematical framework is presented for the treatment of the bidomain equations used to model propagation in cardiac tissue. This framework is independent of the model used to represent membrane ionic currents and incorporates boundary conditions and other constraints. By representing the bidomain equations in the operator notation L phi = F, various algebraic transformations can be expressed as PLQ-1 psi = PF, where P and Q are linear operators. The authors show how previous work fits into this framework and discuss the implications of various transformation for numerical methods of solution. Although such transformations allow many choices of independent variable, these results emphasize the fundamental importance of the transmembrane potential. PMID- 8204982 TI - Fitting epidemiologic follow-up studies with cumulative damage models. AB - The use of an extended version of the cumulative damage model to identify and quantify cancer risk arising from a specified exposure is outlined. For this, a strategy to fit the model to individual data coming from epidemiologic follow-up studies is described. Two statistical problems are addressed: first, the regularity of the model has to be ascertained to allow the application of maximum likelihood and likelihood-ratio methods for parameter estimation and testing. Second, a statistical test has to be found that permits testing goodness of fit in the setting of parameter estimation with individual data. As an example, these methods are applied to the data of a cohort study on mortality among stainless steel welders in the Federal Republic of Germany. The results show that the model fits the data well and confirms a carcinogenic effect of stainless steel welding among welders. Some distinguishing characteristics of the model, especially its prediction of a potentially decreasing relative risk despite ongoing carcinogenic exposure, are discussed. PMID- 8204983 TI - Inverse electrocardiographic transformations: dependence on the number of epicardial regions and body surface data points. AB - The inverse problem of electrocardiography, the computation of epicardial potentials from body surface potentials, is influenced by the desired resolution on the epicardium, the number of recording points on the body surface, and the method of limiting the inversion process. To examine the role of these variables in the computation of the inverse transform, Tikhonov's zero-order regularization and singular value decomposition (SVD) have been used to invert the forward transfer matrix. The inverses have been compared in a data-independent manner using the resolution and the noise amplification as endpoints. Sets of 32, 50, 192, and 384 leads were chosen as sets of body surface data, and 26, 50, 74, and 98 regions were chosen to represent the epicardium. The resolution and noise were both improved by using a greater number of electrodes on the body surface. When 60% of the singular values are retained, the results show a trade-off between noise and resolution, with typical maximal epicardial noise levels of less than 0.5% of maximum epicardial potentials for 26 epicardial regions, 2.5% for 50 epicardial regions, 7.5% for 74 epicardial regions, and 50% for 98 epicardial regions. As the number of epicardial regions is increased, the regularization technique effectively fixes the noise amplification but markedly decreases the resolution, whereas SVD results in an increase in noise and a moderate decrease in resolution. Overall the regularization technique performs slightly better than SVD in the noise-resolution relationship. There is a region at the posterior of the heart that was poorly resolved regardless of the number of regions chosen. The variance of the resolution was such as to suggest the use of variable-size epicardial regions based on the resolution. PMID- 8204984 TI - An approximate solution to the periodic bidomain equations in one dimension. AB - An approximate, computationally tractable solution is proposed for the potentials in the bidomain model with periodic intracellular junctions (the periodic bidomain model). This new approach is based on the one-dimensional rigorous spectral method described previously by Trayanova and Pilkington (IEEE Trans. Biomed. Eng., May 1993). The total solution to the one-dimensional periodic bidomain problem is decomposed in the spectral domain into solutions to (1) the single-fiber classical bidomain problem in which the intracellular conductivity value incorporates the average contribution from cytoplasm and junction and (2) the "junctional" potential problem due to the presence of junctions at discrete locations alone. Solving for the junctional term rigorously requires most of the numerical effort in the solution for the periodic bidomain potentials. Here the junctional potential is found approximately with little numerical effort. A comparison between the rigorous and the approximate solutions serves as a justification for the proposed approximate solution procedure. The procedure outlined in this paper is applicable to higher spatial dimensions where both tissue anisotropy and junctional inhomogeneities play a role in establishing the transmembrane potential distribution. PMID- 8204985 TI - A stem cell model for carcinogenesis. AB - A modification to the well-known two-stage model of carcinogenesis with clonal expansion is proposed. A true stem cell is applied to the production of intermediate cells by incorporating a birth-death process with a reflecting barrier into the model. The distribution of the number of detectable intermediate cell clones is derived, and systems of differential equations are formulated for the cumulative distribution function for the appearance of malignant tumors. The model is applied to data on papilloma formation in a mouse skin painting experiment. Tests for the importance of intermediate cells in tumor incidence can be derived. PMID- 8204987 TI - Nonlinear diffusion of a growth inhibitory factor in multicell spheroids. AB - A mathematical model is presented for the production of a growth inhibitory factor (GIF) within a multicell spheroid. The model is based on the assumption that the GIF diffuses within the spheroid in a nonlinear spatially dependent manner. This is in contrast with previous models, in which the nonlinearity was assumed in the production term. The results of the new model are compared with those of previous models and with experimental data. PMID- 8204986 TI - Piecewise exponential survival curves with smooth transitions. AB - Several models of a population survival curve composed of two piecewise exponential distributions are developed. In one formulation the hazard rate changes at a point that is an unobservable random variable that varies between individuals. The population hazard function may decrease with age even when all individuals' hazards are increasing. In a second formulation, the population hazard function is modeled directly. Several models are fit to the survival history of a cohort of 5751 highly inbred male Drosophila melanogaster and the British coal mining disaster data. PMID- 8204988 TI - Compartmental models and competing risk. AB - General compartmental models are derived using competing risk arguments. When the risk variables are exponential, the results specialize to the standard stationary Markov compartmental model. Iterative methods of solving the fundamental integral equation are given, and the uniqueness of the solution is incidentally established. The analysis is extended to include fixed inputs, orderly and nonorderly stream infusions, and time dependency. The study is motivated by a biological system that evolves through various stages over time. PMID- 8204989 TI - A simplified model for age-dependent population dynamics. AB - The Gurtin-MacCamy model for age-dependent population dynamics is reduced to a single ordinary differential equation by assuming a certain form of the mortality function, which is justified by several biological examples. Some results about harvesting are obtained. PMID- 8204990 TI - A differential-delay model of pasture accumulation and loss in controlled grazing systems. AB - A grazing population dynamics model is proposed where organisms in a grazed population have a fixed life span. The motivating context is that of ruminants grazing grass-dominant pasture. The model takes the form of a differential-delay equation in which the rate of loss of pasture due to senescence at some time depends on the rate at which leaves are reaching maturity at that time. Comparisons are made with data from a continuous grazing experiment due to Bircham and Hodgson (Grass and Forage Science, 38:323-331, 1985), leading to a prediction of 21.9 days for herbage life span. Predictions of herbage utilization are consistent with measured data. The model predicts lower senescence in swards in regrowth than in grazed swards at the same herbage mass. Solutions and equilibria are obtained for the linear form of the model with continuous grazing pressure. Solutions and bounds are obtained for the linear model with intermittent grazing pressure, and its usefulness in modeling grazed pastures is discussed. A delay model is a simple but powerful means of including the concept of fixed herbage life span in grazing modeling. Questions of herbage life span and percentage utilization are naturally contained in the mechanism of a differential-delay model. There are not so well handled by models that treat senescence of herbage empirically. PMID- 8204991 TI - Periodic, quasi-periodic, and chaotic coexistence of two competing microbial populations in a periodically operated chemostat. AB - It is well known that when two microbial populations competing for a single rate limiting nutrient are grown in a chemostat with time-invariant inputs, with competition being the only interaction between them, they cannot coexist, but eventually one of the two populations prevails and the other becomes extinct. It has been suggested that periodic variation of one of the chemostat's operating parameters can stabilize the coexistence state of the two microbial populations. A systematic numerical study of the model equations describing microbial competition in a chemostat with periodically varying dilution rate is performed, and it is shown that coexistence of the competing microbial populations is obtained for a wide range of operating conditions. The coexistence state is usually in the form of limit cycle oscillations. However, cases of chaotic behavior resulting from successive period doublings and quasi-periodicity are also observed. PMID- 8204992 TI - Increased trimipramine plasma levels during fluvoxamine comedication. AB - A depressive patient, a non-responder to trimipramine (TRI), was comedicated first with citalopram (CIT) and then with fluvoxamine (FLUV). Both the TRI-CIT and TRI-FLUV combination treatments led to a worsening of the depressive state and to the appearance of panic attacks. The addition of FLUV to TRI resulted in a twofold increase of the plasma levels of TRI and to a slight increase of its N demethylated and 2-hydroxylated metabolites. These results suggest that the interaction between FLUV and TRI occurred at the level of cytochrome P-450IID6 and cytochrome P-450meph in this patient, phenotyped as an extensive metabolizer of both dextromethorphan and mephenytoin. The adverse effects were possibly due to (a) a pharmacokinetic interaction between CIT and FLUV with TRI and/or (b) alterations in serotonergic and/or dopaminergic neurotransmission. PMID- 8204993 TI - Functional properties of the brain during sleep under subchronic zopiclone administration in man. AB - Zopiclone, a non-benzodiazepine, has been shown to be efficient in the treatment of transient, short-term or chronic sleep disorders. Apart from its hypnotic effects zopiclone has anxiolytic, anticonvulsant and myorelaxant properties and is therefore hardly distinguishable from benzodiazepines. Dependence liability and discontinuation effects have been reported to be less pronounced. Therefore zopiclone seems to be a hypnotic drug which may cause fewer side effects than conventional benzodiazepines. From the electrophysiological point of view one requires from a hypnotic drug the induction of a physiological sleep pattern as well as no alterations of information processing by the brain. The aim of the present study was to investigate the subchronic effect of zopiclone medication on some functional properties of the sleep EEG in healthy subjects. In order to get better insight into the principles of information processing by the brain during sleep and its alterations under the influence of zopiclone we applied some tools from linear system theory to sleep EEG data. For this purpose we investigated late components of auditory and visual evoked potentials during different sleep stages and calculated from these the so-called amplitude-frequency characteristic of the brain. This function describes the relationship between an input and the output of the investigated system. The main advantage of this kind of analysis is that it enables one to detect functional differences during sleep stages. This information can hardly be obtained from conventional spectral analysis. As a result we could demonstrate that under subchronic zopiclone medication no quantitative or qualitative alterations of the functional sleep EEG properties concerning the transfer properties of the brain under auditory and visual stimulation were detectable. PMID- 8204994 TI - Genotypic differences in locomotor stimulation and dopaminergic activity following acute ethanol administration. AB - The effects of increasing doses of ethanol on locomotor activity and on the metabolism of dopamine (DA) in the limbic forebrain and in the striatum of CBA, C57, and NMRI mice were studied. In NMRI mice, low doses of ethanol produced locomotor stimulation which was followed by inhibition of locomotor activity at higher doses. In C57 and CBA animals, ethanol caused only reduction of locomotor activity. A low dose of ethanol (2.25 g/kg, i.p.) produced a significant enhancement of the release of dopamine (measured as the ratio DOPAC/DA) in limbic brain structures of all animals with no corresponding effect in the striatum. A high dose of ethanol (4.5 g/kg, i.p.) significantly increased the DOPAC/DA ratio both in the limbic forebrain and in the striatum of all animals. The significance of these behavioral and biochemical observations with regard to genetic aspects of the role of DA in the stimulatory/reinforcing properties of ethanol and to previously observed genetic differences in other neurotransmitter systems, especially GABA and glutamate, is discussed. PMID- 8204995 TI - The effect of haloperidol and naloxone on excessive grooming behavior of cats. AB - In a double-blind cross-over study the effect of a single injection of naloxone (1 mg/kg s.c.) was investigated in 12 cats which suffered from excessive grooming with subsequent coat damage. Based on clinical observations and reports of the owners, naloxone had a beneficial effect on grooming which lasted between 2.5 weeks and 6 months (median 3 months). In another double-blind placebo-controlled study the effect of a single injection of haloperidol (2 mg/kg i.v.) was investigated in 20 cats with excessive grooming. Within 24 h haloperidol significantly reduced the time spent grooming. Four months after the injection no effect remained in nine of 10 cats injected with a placebo solution, whereas six of 10 cats injected with haloperidol the improved condition of the coat was maintained. It is hypothesized that naloxone is only effective in counteracting recently developed stereotypic behaviors and that haloperidol rather reduces stereotyped behaviors over a longer period. PMID- 8204996 TI - Adverse effects associated with the short-term treatment of panic disorder with imipramine, alprazolam or placebo. AB - Side effects play a significant role in the selection of drugs to be used in panic disorder/agoraphobia whose polyphobic symptomatology often includes a suspiciousness about taking drugs and a fear of undesired side effects which may lead to the refusal of treatment. The safety, side effects and patients' acceptance of alprazolam and imipramine versus placebo were evaluated in 1168 subjects with panic disorder/agoraphobia who had been enrolled in the second phase of the Upjohn World Wide Panic Study. Side effects that worsened over baseline to a greater extent with alprazolam than with imipramine and placebo were sedation, fatigue/weakness, memory problems, ataxia and slurred speech. In the imipramine group blurred vision, tachycardia/palpitations, insomnia, sleep disturbance, excitement/nervousness, malaise, dizziness/faintness, headache, nausea/vomiting and decrease in appetite were worse than in the other groups. In the placebo group the anxious symptoms were most prominent. The highest level of compliance was shown in the alprazolam-treated group and the lowest in the placebo-treated group. Strong predictors of side effects were not observed. If a side effect profile is known, it will be easier for a clinician to choose the right drug and the appropriate management by taking into account compliance, safety and efficacy in each patient under treatment. Further information about side effects in long-term maintenance treatment would be of great clinical pertinence in ensuring safety and enhancing patients' quality of life. PMID- 8204997 TI - Are serotonergic reuptake inhibitors more potent in reducing suicidality? An empirical study on paroxetine. AB - There is some empirical evidence that selective serotonin reuptake inhibitors reduce suicidal ideas faster than other antidepressants. These findings are well in line with the theory of a serotonergic hypofunction in suicidal patients. To test this hypothesis the data of a 6-week double-blind control-group study comparing paroxetine versus amitriptyline were analyzed with respect to suicidality. The global antidepressive efficacy was comparable under dosages of 30 mg paroxetine or 150 mg amitriptyline per day. A differentiated analysis failed to confirm the hypothesis of a faster reduction of suicidal cognitions by paroxetine. PMID- 8204998 TI - Guidelines on psychotropic drugs for the EC. Committee for Proprietary Medicinal Products. European Economic Community. PMID- 8204999 TI - Lack of association between platelet tritiated imipramine binding and clinical status of depressed patients on chronic antidepressant treatment. AB - Platelet tritiated imipramine binding (Bmax) was studied in 33 depressed patients, before and after 1 and 4 weeks of antidepressant treatment, and in 34 healthy volunteers. The Bmax was significantly lower (-21%) in drug-free depressed patients than in controls and increased significantly as early as the first week of treatment to reach the control value, in parallel with a 38% decrease in the Hamilton depression rating scale (HDRS) score. After 4 weeks of treatment, the Bmax was still normal and remained significantly higher than the baseline value, while the clinical state of the patients had greatly improved (a 63% decrease in the HDRS score). However, an increase in the Bmax also occurred in non-responders to treatment. In addition, we observed that the ability of the treatment to increase the Bmax depended on the pharmacological profile of the drug used. The present results show that, in patients on antidepressant medication, platelet tritiated imipramine binding normalization cannot be considered as a marker of clinical remission. PMID- 8205000 TI - Developmental and hormonal regulation of sunflower helianthinin genes: proximal promoter sequences confer regionalized seed expression. AB - DNA elements involved in the regulation of two sunflower helianthinin genes were identified by analysis of beta-glucuronidase (GUS) expression in transgenic tobacco driven by sequences derived from the 5' upstream regions of these genes. A 2.4-kb upstream region of the helianthinin gene HaG3-A conferred rigorous developmental GUS expression in transgenic tobacco seeds with no significant GUS activity in nonembryonic tissues. Regions of the helianthinin upstream regulatory ensemble (URE) conferred ectopic expression in nonembryonic tissues when analyzed outside of the context of the complete helianthinin regulatory complex. A proximal promoter region was identified that conferred significant GUS expression in seeds but not in leaves of transgenic tobacco. Three sequence motifs that bind to seed nuclear proteins were identified in the proximal promoter region; mutations in these motifs significantly reduced the level of nuclear protein binding. Another important class of cis-regulatory elements was identified in the helianthinin URE that conferred abscisic acid-responsive GUS expression. In the full-length helianthinin URE, these elements only responded to abscisic acid in the developing seed, suggesting that the helianthinin gene contains additional regulatory elements, possibly in the proximal promoter region, that ensure hierarchical control in the developing seed. PMID- 8205001 TI - Genetic and molecular analysis of an allelic series of cop1 mutants suggests functional roles for the multiple protein domains. AB - The Arabidopsis protein COP1, encoded by the constitutive photomorphogenic locus 1, is an essential regulatory molecule that plays a role in the repression of photomorphogenic development in darkness and in the ability of light-grown plants to respond to photoperiod, end-of-day far-red treatment, and ratio of red/far-red light. The COP1 protein contains three recognizable structural domains: starting from the N terminus, they are the zinc binding motif, the putative coiled-coil region, and the domain with multiple WD-40 repeats homologous to the beta subunit of trimeric G-proteins (G beta). To understand the functional implications of these structural motifs, 17 recessive mutations of the COP1 gene have been isolated based on their constitutive photomorphogenic seedling development in darkness. These mutations define three phenotypic classes: weak, strong, and lethal. The mutations that fall into the lethal class are possible null mutations of COP1. Molecular analysis of the nine mutant alleles that accumulated mutated forms of COP1 protein revealed that disruption of the G beta-protein homology domain or removal of the very C-terminal 56 amino acids are both deleterious to COP1 function. In-frame deletions or insertions of short amino acid stretches between the putative coiled-coil and G beta-protein homology domains strongly compromised COP1 function. However, a mutation resulting in a COP1 protein with only the N-terminal 282 amino acids, including both the zinc binding and the coiled-coil domains, produced a weak phenotypic defect. These results indicated that the N-terminal half of COP1 alone retains some activity and a disrupted C terminal domain masks this remaining activity. PMID- 8205002 TI - Phosphorylation and calcium binding properties of an Arabidopsis GF14 brain protein homolog. AB - Arabidopsis GF14 omega was originally described because of its apparent association with a DNA-protein complex; it is a member of the 14-3-3 kinase regulatory protein family that is conserved throughout eukaryotes. Here, we demonstrated that recombinant GF14 omega is expressed in Escherichia coli as a dimer. Blot binding and electrophoretic mobility shift analyses indicated that GF14 omega binds calcium. Equilibrium dialysis further demonstrated that GF14 omega binds an equimolar amount of calcium with an apparent binding constant of 5.5 x 10(4) M-1 under physiological conditions. The C-terminal domain, which contains a potential EF hand motif, is responsible for the calcium binding. The C terminal domain also cross-reacted with the anti-GF14 omega monoclonal antibody. In addition, GF14 omega is phosphorylated by Arabidopsis protein kinase activity at a serine residue(s) in vitro. Therefore, GF14 omega protein has biochemical properties consistent with potential signaling roles in plants. The presence of a potential EF hand-like motif in the highly conserved C terminus of 14-3-3 proteins together with the calcium-dependent multiple functions attributed to the 14-3-3 proteins indicate that the C terminus EF hand is a common functional element of this family of proteins. PMID- 8205003 TI - The never ripe mutation blocks ethylene perception in tomato. AB - Seedlings of tomato fruit ripening mutants were screened for their ability to respond to ethylene. Ethylene induced the triple response in etiolated hypocotyls of all tomato ripening mutants tested except for one, Never ripe (Nr). Our results indicated that the lack of ripening in this mutant is caused by ethylene insensitivity. Segregation analysis indicated that Nr-associated ethylene insensitivity is a single codominant trait and is pleiotropic, blocking senescence and abscission of flowers and the epinastic response of petioles. In normal tomato flowers, petal abscission and senescence occur 4 to 5 days after the flower opens and precede fruit expansion. If fertilization does not occur, pedicel abscission occurs 5 to 8 days after petal senescence. If unfertilized, Nr flowers remained attached to the plant indefinitely, and petals remained viable and turgid more than four times longer than their normal counterparts. Fruit development in Nr plants was not preceded by petal senescence; petals and anthers remained attached until they were physically displaced by the expanding ovary. Analysis of engineered 1-aminocyclopropane-1-carboxylate (ACC) synthase overexpressing plants indicated that they are phenotypic opposites of Nr plants. Constitutive expression of ACC synthase in tomato plants resulted in high rates of ethylene production by many tissues of the plant and induced petiole epinasty and premature senescence and abscission of flowers, usually before anthesis. There were no obvious effects on senescence in leaves of ACC synthase overexpressers, suggesting that although ethylene may be important, it is not sufficient to cause tomato leaf senescence; other signals are clearly involved. PMID- 8205004 TI - Light-regulated modification and nuclear translocation of cytosolic G-box binding factors in parsley. AB - Functional cell-free systems may be excellent tools with which to investigate light-dependent signal transduction mechanisms in plants. By evacuolation of parsley protoplasts and subsequent silicon oil gradient centrifugation of lysed evacuolated protoplasts, we obtained a highly pure and concentrated plasma membrane-containing cytosol. Using GT- and G-box DNA elements, we were able to demonstrate a specific localization of a pool of G-box binding activity and factors (GBFs) but not one of GT-box binding activity in this cytosolic fraction. The DNA binding activity of the cytosolic GBFs is modulated in vivo as well as in vitro by light and phosphorylation/dephosphorylation activities. The regulation of cytosolic G-box binding activity by irradiation with continuous white light and phosphorylation correlates with a light-modulated transport of GBFs to the nucleus. This was shown by a GBF-antibody cotranslocation assay in permeabilized, cell-free evacuolated parsley protoplasts. We propose that a light-regulated subcellular displacement of cytosolic GBFs to the nucleus may be an important step in the signal transduction pathway coupling photoreception to light dependent gene expression. PMID- 8205005 TI - Genotype-phenotype correlations in beta-thalassemias. AB - In this paper we review the molecular basis of the marked heterogeneity of the thalassemia syndromes as well as the relative implications for carrier screening and prenatal diagnosis. The classical phenotype of heterozygous beta-thalassemia may be modified by a number of environmental and genetic interacting factors- among which the most relevant are: (1) coinheritance of alpha-thalassemia, which may normalize the red blood cell indices; (2) the presence of a mild beta thalassemia mutation; (3) cotransmission of delta-thalassemia which may reduce the increase of HbA2 typical of heterozygous beta-thalassemia to normal values and (4) the presence of a silent mutation which can be defined only by imbalanced beta-globin chain synthesis. A number of molecular mechanisms are able to produce the non transfusion dependent attenuated forms of thalassemia syndromes referred to as thalassemia intermedia. The most common are homozygosity for mild beta thalassemia mutations, coinheritance with homozygous beta-thalassemia of alpha thalassemia or genetic determinants able to sustain a continuous production of HbF in adult life or the presence of heterozygosity for hyperunstable globin variants. PMID- 8205006 TI - Mechanisms of the escape phase of myeloma. AB - In multiple myeloma the duration of plateau is an important clinical and biological determinant of quality of life and survival. During plateau phase, the tumour is in an indolent state, as manifested by a low labelling index of plasma cells and other proliferative markers, e.g. the thymidine kinase level. The mechanism by which plasma cells escape from this indolent phase to a more aggressive phase of this disease is unknown, but a number of possible mechanisms have been postulated. These include loss of immunoregulation, clonal evolution, cytokine dysfunction and oncogene activation or tumour suppressor gene dysfunction. As current chemotherapy protocols do not appear to be able to eradicate the malignant clone, understanding the nature of the indolent phase of the malignant clone and the reasons for its escape from this phase are very important and may provide new options for disease control. PMID- 8205007 TI - Management of chronic myeloid leukaemia. PMID- 8205008 TI - Cytogenetics in acute myeloid leukaemia. AB - A wealth of literature spanning 20 years describing cytogenetic abnormalities in acute myeloid leukaemia (AML) already exists. It ranges from single case reports of unusual abnormalities to large multicentre studies of hundreds of cases. A landmark publication was the Fourth International Workshop on Chromosomes in Acute Leukaemia which established a base line for diagnosis, prognosis and frequency of chromosome abnormalities in AML. Two large sources of information are a book, 'The Chromosomes in Human Cancer and Leukemia' and a catalogue of chromosome abnormalities, which aims to list all chromosome abnormalities described in the scientific and medical literature from 1973, when the widespread use of banding techniques, enabled the precise definition of the chromosome breakpoints. In this review the common cytogenetic abnormalities seen in AML with reference to associations with the French-American-British (FAB) classification, their possible prognostic significance and their associated molecular biology are summarized. PMID- 8205009 TI - Antithrombin and its inherited deficiencies. AB - Human antithrombin is the major inhibitor of the coagulation serine proteases accounting for approximately 80% of the thrombin inhibitory activity of plasma. It is a member of the serpin family of serine protease inhibitors and in common with some other members of this family it undergoes a dramatic increase in its inhibitory activity in the presence of heparin and other sulphated glycosaminoglycans. Two functional domains in antithrombin are recognised, the reactive site domain which interacts with the active site serine residue of the protease and the heparin binding domain. The gene for antithrombin has been cloned and its entire nucleotide sequence determined. A deficiency or functional abnormality of antithrombin may result in an increased risk of thromboembolic disease. Such deficiencies are estimated to affect as many as 1:300 of the general population and 3 to 5% of patients with thrombotic disease. On the basis of functional and immunological antithrombin assays, antithrombin deficiency may be subdivided into Types I and II. Type I disease is due to a wide variety of heterogeneous DNA mutations whilst in Type II disease missense mutations leading to single amino acid substitutions have been identified in all cases. Clinically, Type I antithrombin deficiency is associated with recurrent thromboembolic disease whereas in Type II deficiency the risk of thrombosis is closely related to the position of the mutation within the protein. Thus, heterozygotes with mutations within the heparin binding domain of antithrombin have a relatively low risk of thrombosis compared to those with mutations at or close to the reactive site of the molecule. PMID- 8205010 TI - Biochemistry of factor X. AB - Factor X circulates as a serine protease which is converted to the active form at the point of convergence of the intrinsic and extrinsic coagulation pathways. Subsequently, the enzymatic species, factor Xa, is involved in macromolecular complex formation with its cofactor factor Va, a phospholipid surface and calcium to convert prothrombin into thrombin. The gene encoding factor X shares a number of structural and organisational features in common with the other vitamin K dependent coagulation proteins, suggesting that they have evolved from a common ancestral gene. Each of the exons encoding these proteins can be considered as a module coding for a homologous domain in each protein. These structural domains in factor X are responsible for specific functional properties including gamma carboxylase recognition, calcium binding, phospholipid surface interaction, as well as cofactor and substrate binding. Studies of recombinant proteins and proteolytic fragments continue to provide significant insight into structure function relationships of the protein modules within factor X. PMID- 8205011 TI - New approaches to treating oesophageal cancer. PMID- 8205012 TI - Aspirin and pre-eclampsia. PMID- 8205013 TI - Syncope. PMID- 8205014 TI - Treating dizziness with vestibular rehabilitation. PMID- 8205015 TI - Antenatal screening for syphilis. PMID- 8205016 TI - Alcohol, accidents, and aggression. PMID- 8205017 TI - Juvenile onset inflammatory bowel disease: height and body mass index in adult life. AB - OBJECTIVE: To establish the frequency of permanent growth failure in juvenile onset inflammatory bowel disease. DESIGN: Measurement of height and weight in a geographically based cohort at a mean of 14 (range 5.2-29.5) years after diagnosis. Comparison with data from surveys of British adults in 1980 and 1987. SETTING: NHS hospitals throughout Scotland. SUBJECTS: 105 Children admitted to hospital during 1968-83 who fulfilled diagnostic criteria for Crohn's disease or ulcerative colitis and lived in specified regions. 87 were aged over 18 and living in Britain at follow up. MAIN OUTCOME MEASURES: Height, weight, body mass index, and sexual maturity. RESULTS: All patients were sexually mature. 67 of the 70 patients examined were of normal height, and three women with Crohn's disease were abnormally short. Weight and body mass index were normal in all patients with ulcerative colitis. Patients with Crohn's disease had significantly lower weight than those with ulcerative colitis (men 66.8 (9.5) kg v 78.4 (13.8) kg, P = 0.04; women 51.5 (8.2) kg v 63.0 (12.1) kg, P < 0.02) irrespective of disease activity. Body mass index was also significantly lower than the normal distribution (P < 0.01). Growth retardation was not mentioned as a problem for any of the 17 patients interviewed only by telephone. CONCLUSIONS: Despite growth retardation in the teenage years most young people with inflammatory bowel disease will eventually achieve normal height. Reasons for lower weight in patients with Crohn's disease remain to be established. PMID- 8205019 TI - National trends in birth weight: implications for future adult disease. PMID- 8205018 TI - Cardioprotective effect of hormone replacement therapy in postmenopausal women: is the evidence biased? AB - OBJECTIVE: To quantify the effect of selection of relatively healthy women in studies reporting reduced relative risk for cardiovascular disease in postmenopausal women taking hormone replacement therapy. DESIGN: Review of the follow up studies reported in three recent meta-analyses to determine the effect of oestrogen therapy on both total cancer and cardiovascular disease. The same standard statistical methods as in the original analyses were used. MAIN OUTCOME MEASURES: Relative risks of total cancer and cardiovascular disease. RESULTS: In most of the follow up studies the relative risk for total cancer was below 1. The studies that showed the largest reduction in cardiovascular disease also showed the largest reduction in cancer, indicating a healthy cohort effect. Although heterogeneity within the studies prevented pooling, the best estimate for the protective effect on total cancer was a relative risk of 0.83 among women taking oestrogen (95% confidence interval 0.71 to 0.96), while in the same studies the relative risk for cardiovascular disease was 0.57 (0.50 to 0.64). CONCLUSIONS: Unintended selection of relatively healthy women for oestrogen therapy may have influenced the reported beneficial effect of oestrogen therapy on cardiovascular disease. It is unclear how much of the cardioprotection is due to this selection. Universal preventive hormonal replacement therapy for postmenopausal women is unwarranted at present. PMID- 8205020 TI - Axillary sweating in clinical assessment of dehydration in ill elderly patients. PMID- 8205021 TI - Using patient and general practice characteristics to explain variations in cervical smear uptake rates. AB - OBJECTIVES: To produce practice and patient variables for general practices from census and family health services authority data, and to determine the importance of these variables in explaining variation in cervical smear uptake rates between practices. DESIGN: Population based study examining variations in cervical smear uptake rates among 126 general practices using routine data. SETTING: Merton, Sutton, and Wandsworth Family Health Services Authority, which covers parts of inner and outer London. MAIN OUTCOME MEASURE: Percentage of women aged 25-64 years registered with a general practitioner who had undergone a cervical smear test during the five and a half years preceding 31 March 1992. RESULTS: Cervical smear uptake rates varied from 16.5% to 94.1%. The estimated percentage of practice population from ethnic minority groups correlated negatively with uptake rates (r = -0.42), as did variables associated with social deprivation such as overcrowding (r = -0.42), not owning a car (r = -0.41), and unemployment (r = 0.40). Percentage of practice population under 5 years of age correlated positively with uptake rate (r = 0.42). Rates were higher in practices with a female partner than in those without (66.6% v 49.1%; difference 17.5% (95% confidence interval 10.5% to 24.5%)), and in computerised than in non computerised practices (64.5% v 50.5%; 14.0% (6.4% to 21.6%)). Rates were higher in larger practices. In a stepwise multiple regression model that explained 52% of variation, five factors were significant predictors of uptake rates: presence of a female partner; children under 5; overcrowding; number of women aged 35-44 as percentage of all women aged 25-64; change of address in past year. CONCLUSIONS: Over half of variation in cervical smear uptake rates can be explained by patient and practice variables derived from census and family health services authority data; these variables may have a role in explaining variations in performance of general practices and in producing adjusted measures of practice performance. Practices with a female partner had substantially higher uptake rates. PMID- 8205022 TI - Doctors with problems in an NHS workforce. AB - OBJECTIVES: To describe the incidence, nature, and implications of serious disciplinary problems among the medical staff of a large NHS hospital workforce. DESIGN: Descriptive study with analysis of case records. SETTING: Northern Health Region, an administrative area within the NHS covering a population of three million. SUBJECTS: Forty nine hospital doctors: 46 consultants and three associate specialists. MAIN OUTCOME MEASURES: The nature of the problems encountered within the doctors' practice, and the types of action taken by the employing authority. RESULTS: Over a five year period concerns serious enough to warrant the consideration of disciplinary action were raised about 6% of all senior medical staff (49/850). Ninety six types of problem were encountered, and were categorised as poor attitude and disruptive or irresponsible behaviour (32), lack of commitment to duties (21), poor skills and inadequate knowledge (19), dishonesty (11), sexual matters (seven), disorganised practice and poor communication with colleagues (five), and other problems (one). Twenty five of the 49 doctors retired or left the employer's service, whereas 21 remained in employment after counselling or under supervision. CONCLUSIONS: Existing procedures for hospital doctors within the NHS are inadequate to deal with serious problems. Dealing with such problems requires experience, objectivity, and a willingness to tolerate unpleasantness and criticism. Because most consultants' contracts are now held by NHS trust hospitals, however, those who had developed skill over the years in handling these complex issues are now no longer involved. PMID- 8205023 TI - Treating childhood asthma in Singapore: when West meets East. AB - Though Western medicines and ideas about asthma have become popular in many Asian nations, local beliefs about treatment prevail. The multiracial society of Singapore shows a variety of beliefs about causes of asthma attacks (for example, the balance of yin and yang) and types of treatment--herbal remedies, inhaled versus eaten medicines, the influence of Ramadan. Many of the cultural practices mentioned are probably preserved among south east Asian minorities residing in the United Kingdom. Eastern treatments typically take a holistic approach to asthma and do not ignore the psychosomatic component of the disorder. PMID- 8205024 TI - Who cares about equity in the NHS? AB - The concept of equity in relation to the National Health Service in Britain encompasses not one but at least eight distinct principles. Until the 1980s the NHS had a good record of incorporating these principles into practice. Throughout the 1980s, however, there has been a pronounced change, with the gradual introduction of business values into the service, culminating in the market based reforms of the 1990s. Several recent policies seem to be taking the NHS away from the goal of an equitable system--for example, the new arrangements for community care and the incentives within contracting to select patients on financial grounds. To restore equity as a value demands priority for ethical values, monitoring of policies for their effects on equity, some national planning, and a new debate about the entitlement to services such as continuing care. PMID- 8205025 TI - Cancer chemotherapy: identifying novel anticancer drugs. AB - There are now around 60 cytotoxic drugs licensed for use in cancer therapy in the United Kingdom. For certain malignancies such as childhood cancers, haematological malignancies, and germ cell tumours chemotherapy has been pivotal to the substantial improvement in therapeutic outcome achieved over the past 10 years. In contrast, improvements in the systemic management of adult solid tumours have been less dramatic. There is a clear and urgent need for new, more effective drugs for lung, breast, and colorectal malignancies. This paper examines the processes in identifying, developing, and evaluating new drugs with anticancer activity. PMID- 8205026 TI - ABC of sports medicine. Benefits of exercise in health and disease. PMID- 8205027 TI - Chronic fatigue syndrome. Distinguish between syndromes... PMID- 8205028 TI - Chronic fatigue syndrome. ...and study them separately. PMID- 8205029 TI - Chronic fatigue syndrome. Preliminary report misrepresented. PMID- 8205030 TI - Chronic fatigue syndrome. Self help groups give valuable support. PMID- 8205031 TI - Chronic fatigue syndrome. Immunological findings vary between populations. PMID- 8205032 TI - Chronic fatigue syndrome. Prevalence study overlooked. PMID- 8205033 TI - Chronic fatigue syndrome. ME Association is honest about prognosis. PMID- 8205034 TI - Blood pressure and myocardial infarction. Low blood pressure can be hazardous. PMID- 8205035 TI - Reactive arthritis. May develop in patients with HIV infection. PMID- 8205036 TI - Reactive arthritis. Consider combination treatment. PMID- 8205037 TI - Cutaneous T cell lymphomas. PMID- 8205038 TI - Original description of Kaposi's sarcoma. PMID- 8205039 TI - [The effect of serotonin on pain sensitivity and the nociceptive reactions of the blood pressure]. AB - When injected intravenously (1 mg/kg) and intrathecally (100 micrograms) to rats, serotonin produced an analgesic effect in thermal pain and failed to affect nociceptive responses under electric irritation. When given in the analgesic dose, it unchanged the baseline level of blood pressure, but enhanced its nociceptive pressor responses. Naloxone (0.1 mg/kg) reduced the sedative action of serotonin and prevented the increase of pressor responses of blood pressure induced by its intrathecal administration. PMID- 8205040 TI - [The effect of fenibut on the ultrastructure of the brain mitochondria in traumatic edema and swelling]. AB - Rat experiments using electron microscopy have established that profound destructive changes occur in the mitochondria in the intra- and perifocal traumatic area in dynamics of traumatic edema-swelling. With phenibut, 50 mg/kg, there is an increase in the number of mitochondria in the brain tissue of the perifocal area, their destructive changes are less pronounced. It is assumed that the positive effect of phenibut on brain bioenergetic processes in the posttraumatic period is associated with the changes. PMID- 8205041 TI - [The effect of dimephosphon, sermion and piracetam on the reactivity of the cerebral vessels, on local cerebral blood flow and on oxygen tension in brain tissue]. AB - The paper gives the results of experimental and clinical studies of the nootropic agents dimephosphone, sermion, and piracetam on local cerebral circulation, cerebrovascular responsiveness and O2 tension. The vasoactivity of the parameters studied has been shown to be displayed by their ability to normalize cerebrovascular responsiveness and it is associated with decreased brain tissue oxygen consumption when dimephosphone is applied and with its increased one when sermion and piracetam are used. PMID- 8205042 TI - [The effect of cytochrome c preparations on the cerebral circulation in cerebral ischemia]. AB - Biotechnological cytochrome c, heme-tetradecapeptide (HTDP) and animal cytochrome c were studied for their effects on intact and brain ischemic rats. In the latter case, the compounds were administered before ischemia induction and 15 min after artery ligation. It was found that the cytochrome c preparations did not virtually affect the cerebral circulation in intact rats. In cerebral ischemia, the cytochrome C preparations increased circulation, showing their more profound effects in case of preadministration of the drugs. The dose-independent effects of HTDP may be associated with the higher transmembranous permeability and the saturation phenomenon of this compound. PMID- 8205043 TI - [The effect of dalargin on the course of experimental cardiac arrhythmias]. AB - Five models of arrhythmias (aconitine-, calcium chloride- and low-sodium-induced models on rats, coronary artery ligation and reperfusion in dogs) were used to study the antiarrhythmic and antifibrillatory effects. The latters were not inferior to those shown by the well-known antiarrhythmics. The mechanisms of the action of dalargin are discussed in the paper. PMID- 8205044 TI - [The effect of different concentrations of strophanthin K on the chrono- and inotropic parameters of the isolated myocardial preparation and its oxygen consumption]. AB - The contraction rate and force of the myocardium and its oxygen consumption under the action of various strophanthin-K concentrations for 10 min after its administration into the cuvette were studied in the experiments on the isolated frog atria contracting in the isometric mode. There was a two-phase response of cardiac glycoside, which depended on the time of its action and concentration. PMID- 8205045 TI - [The effect of calcium antagonists on the biochemical and immune status of hypertension patients]. AB - The immunological and biochemical parameters were studied in patients with Stage II hypertensive disease (HD) before and 2 months after course treatment with calcium antagonists of the dihydropyridine series (siscor and nitrepine). The metabolic mechanisms of the therapeutical action of these drugs were found to affect all specific features of the immune and biochemical status typical of hypertensives. One should identify the priority links which are unambiguously positive and the next links which rank to them, i. e. those manifested themselves in impaired adaptive processes whereby the sick body ensures protection from the disease. The priority links include reduction of hypercortisole- and insulinemia, increase in incretion of testosterone to the reference values, stabilization and sensitization of cellular membranes, decrease of beta 2-microglobulinemia, as well as moderate activation of the immune system and mechanisms of protein synthesis in the cells. The latter links comprise a drop of alpha-cholesterol (HDL) in persistent hypertriglyceridemia, additional tension of hepato- and cardiomyocytic functions, a tendency to cell aging and, partially, reversion of the established sexual hormone ratio. PMID- 8205046 TI - [The pharmacological properties of a modified estrogen 11-nitrate-3-acetate-9 alpha, 11 beta-dioxyestrone]. AB - The experiments on 715 adult non-inbred female rats and 111 Wistar male rats have established that the estrogen 11-nitrate of 3-acetoxy-9 alpha,11 beta-dioxyestra 1,3,5(10)-trien-17-one (11-nitrate of dioxyestron (NDE-As) has an oral contraceptive activity which is equal to ethynylestradiol (EE). A combined 14-day administration of NDE-As with various gestagens produces a higher contraceptive effect that does EE used in combination with the same gestagens. A 30-day use of NDE-As with combined acetomepregenol (AMP) results in a more significant and prolonged secretion of luteinizing hormone than does the EE-AMP combination. Unlike ethynylestradiol, NDE-As has no hypertriglyceridemic effect when given in oral doses of 0.25 and 1.25 mg/kg body weight. PMID- 8205047 TI - [The effect of fluorinated prostaglandins on platelet aggregation]. AB - The effects of fluorodeoxy prostanoids on platelet aggregability were studied. It was shown that introduction of fluorine into positions 9, 11 or 15 of prostaglandin F2 alpha led to enhanced proaggregation activity. The most active compound among fluorodeoxy analogs was 15-fluoro derivative; bisfluoro analog was moderately active, and 11-fluoro compound had the least activity. In the group of fluorodeoxy prostaglandins E2, a contrary effect was registered. Thus, the most active compound was 1-fluoride and the least, 15-fluoride. The incorporation of fluorine into position 15 of prostacyclin led to insignificantly lower antiaggregatory activity just as this modification of 6-keto-prostaglandin F1 alpha was accompanied by a dramatic increase in its ability to inhibit platelet aggregation. PMID- 8205048 TI - [The antithrombotic action of a protein C activator from the venom of Agkistrodon blomhoffi ussuriensis in thrombus formation in an extracorporeal shunt in rats]. AB - An antithrombotic action of the protein C (PC) activator from the venom of Agkistrodon blomhoffi ussuriensis on the model of platelet-dependent thrombosis in the arteriovenous shunt in rats was under investigation. Administration of the PC activator to rats resulted in a dose-dependent prolongation of the thrombus formation time, in a decrease in PC and factor V levels in blood and in APTT prolongation. There were no changes in the tissue-type plasminogen activator level and in the ADP- or epinephrine-induced platelet aggregation, but platelet adhesion to glass decreased. The possible mechanism of the antithrombotic action of the PC activator appeared to be the factor V inactivation mediated by protein C activation and the decrease in platelet adhesion. PMID- 8205049 TI - [The mechanism of the immunostimulating action of trimezon]. AB - The influence of various concentrations (10(-9) - 10(-6) M) of the new immunostimulator trimezon of 8-aza-D-homogonan range upon in vitro proliferation of human lymphocytes, stimulated by PHA 0.5-10.0 micrograms/ml), was investigated by 3H-thymidine incorporation analysis. The maximal stimulating effect of trimezon (by 2.5 times) was found at trimezon concentration of 10(-8) M and at blast transformation optimal PHA concentration of 1 microgram/ml. In the models of the induction of lymphocyte suppressor activity by ConA high concentrations in vitro and by syngeneic mouse hyperimmunized cell transfer in vivo was demonstrated the ability of trimezon to increase the activity of both helper and suppressor sets of regulation mechanisms of immune response. This characterises trimezon as a true immunomodulator. PMID- 8205051 TI - [The effect of iodine-containing x-ray contrast media on water status in the blood plasma]. AB - The impact of radio-opaque agents on human blood plasma water pool was studied by using relaxation proton magnetic resonance methods with a pulse gradient of magnetic field. The findings suggest that blood plasma water imbalance was induced by human serum albumin dehydration processes after RCN-HSA interaction. PMID- 8205050 TI - [The effect of calcium antagonists on the development of inflammatory edema in rats]. AB - The calcium antagonists verapamil and nifedipine were shown to attenuate the development of carrageenin-induced rat paw inflammatory edema. Oral nifedipine exerted more pronounced antiedematous dose-dependent effects. PMID- 8205052 TI - [The effect of x-ray contrast media on the blast transformation of human peripheral blood T-lymphocytes in vitro]. AB - The effects of radiopaque agents on peripheral blood T-lymphocyte blast transformation were in vitro studied in healthy donors. It was shown that depending on the dose and type, radiopaque agents activated spontaneous proliferation of these cells and inhibited or activated PGA-induced proliferation. An individual sensitivity of peripheral blood lymphocytes to the radiopaque agents was revealed. There was a positive correlation between the functional response of peripheral blood lymphocytes to PGA and the degree of bilignost-induced inhibition of this reaction. There was also antagonism of some radiopaques in response to peripheral blood T-lymphocyte blast transformation. PMID- 8205053 TI - [The use of a complex cobalt compound as a cyanide antidote]. AB - The medical effect of the cobalt (III) complex compound [Co(DH)2(H2O)2]Cl poisoning by potassium cyanide has been experimentally found. The poisoning has been caused by intravenous potassium cyanide, 1 mg/kg. The aqueous solution of the complex was added the same to cyanide in doses of 40 and 80 mg/kg. The poison and antidote effects were controlled by bioelectrical tests of the brain and heart. The advantage of the preparation is its direct interaction with cyanide and significantly lower doses as compared with the well-known anticyanide antidotes. PMID- 8205054 TI - [The selectivity of the action of muscarinic agonists in vivo]. AB - The experiments to inhibit a tremor reaction induced by various cholinomimetics have established that DED50 of atropine and amedine is significantly indifferent when tremor is caused by pilocarpine, oxotremorine, and aceclidine while the activity of amedine is lower than that of atropine when ezerine, arecoline and galantamine are applied. The comparison of the findings with the data on the selectivity of the above M-cholinolytics leads to the conclusion that in in vivo experiments, the muscarinic agonists are able to show their selectivity against various subtypes of M-cholinoreceptors. The results of in vivo experiments are found to differ from the data on the in vitro selectivity of M-cholinomimetics in some cases. PMID- 8205055 TI - [A method for the quantitative assessment of the withdrawal syndrome in morphine dependent rats]. AB - The evaluation of strength of morphine withdrawal syndrome in rats after the 17th day i. p. morphine administration is proposed as calculation of individual indexes in "open field" test. It is found, that injection 1, 5 or 10 mg/kg of morphine 30 min before testing, decreases the withdrawal syndrome in dose dependent manner. Disappearance of particular withdrawal signs took place in different doses of morphine pretreatment. According to this effect all the signs were divided into four groups and signs of each group were given by the specificity coefficient (from 0 to 3). The total individual index of the withdrawal syndrome was calculated as a sum of particular signs, multiplied by the particular coefficient. Specificity of significant signs decrease according to the order: "wet dog" shakes, diarrhea, writhings, dyspnea, paw shakes, ptosis, piloerection and teeth chattering. PMID- 8205056 TI - [The clinical and experimental pharmacology of vasopressin agonists and antagonists]. PMID- 8205057 TI - [The action of sodium valproate in central pain syndromes]. AB - A model of acute spinal and phantom pain syndromes caused by the formation of an abnormally increased excitation generator (AIEG) in the system of dorsal horns of the spine was used to study the effects of sodium valproate when used chronically in the phantom pain syndrome, when given in a single dose in the acute pain syndrome and when applied to the spine with disinhibitors inducing the pain syndrome. It was shown that during chronic administration sodium valproate produced a stress-preventive action, but failed to affect pain sensation and to prevent the development of the pain syndrome. When used in the acute pain syndrome, sodium valproate had a marked analgesic effect, and when applied to the spine it substantially reduced the manifestations of the pain syndrome. The action of sodium valproate on the AIEG can be accounted for by the higher GABA level that results in the hyperpolarization of neurons which are a part of AIEG. When the latter is formed and operates in acute and chronic pain syndromes there are differences in the functional activity of the neurochemical structures responsible for the realization of pain reaction components. This is suggested by varying effects of sodium valproate on pain sensation during acute and chronic experiments. PMID- 8205058 TI - Visual readaptation after flash exposure under scotopic conditions. A study using optokinetic nystagmus as an indicator of visual perception. AB - The purpose of the present study was to establish a method for objective measurements of visual readaptation after flash exposures and to define a model for measurements. Influences of target direction, luminance and velocity on optokinetic nystagmus (OKN) were investigated under scotopic conditions. Visual readaptation was measured using OKN as an indicator of visual perception after exposure to a flash. The interval between the triggering of the flash and the reoccurrence of OKN was defined as the visual readaptation time (RAT). A Goldmann perimeter hemisphere was used for flash stimulation. A horizontally moving vertical grating projected inside the hemisphere was used as the OKN stimulus. Eye movements were recorded by DC electrooculography (EOG). The dependence of RAT on the dose of the flash, the wavelength of the flash and the luminance of the OKN target were investigated. The precision of the measurement method was studied. This includes the analysis of the variance due to the experimental occasions, the repeated exposures, the sexes of the subjects, the methods for recognition of OKN and the ways of visual adaptation before measurements. The contributions of retinal receptor and the neural activity to RAT were investigated by electroretinography (ERG). The influences of target direction and luminance on binocular motion perception and OKN as well as monocular OKN were examined at various target velocities. The dependence of the frequency and amplitude of eye jerks during monocular OKN on target luminance and velocity were also examined. It was found that RAT increases with increasing doses of the flash or decreasing luminance of the grating. RAT is most extended after flashes near 520 nm. RAT does not differ between experimental occasions, between a manual and a semi-automatic method for recognition of OKN, between the sexes and between goggle adaptation and ordinary dark adaptation. There is a reduction of RAT due to repeated flash exposures. The data collected indicate that a well-defined model is crucial for measurements of RAT. The measurement of ERG showed that RAT is mediated by both retinal receptor and the neural activities. The receptor component depends on the wavelength of the flash while the neural component is wavelength-independent. Moreover, it was found that motion perception and OKN gain does not differ between right and left target directions. For a given target velocity, motion perception and OKN gain under both binocular and monocular viewing conditions increase with increasing luminance of the target with an exponential decay. The maximum OKN gain decreases as target velocity increases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8205059 TI - Hybrid concept on the mechanical test method of small caliber blood vessel. AB - A mechanical test on small caliber blood vessel is difficult because the strength is very low and the dimension is very small. In the present paper a multifunctional axial test apparatus design is proposed. This has the characteristics such that the load cell and the environmental container for the specimen are built up in terms of cassette, respectively, and thus both are easy to equip and take off, that is, easy to replace. Also, the test methodology by internal pressure for small caliber blood vessels has been proposed. By using both of these methodologies, the characteristics of the mechanical behavior of small caliber blood vessels, such as compliance, stress relaxation, and viscoelastic property have been clarified. An attempt has been made on the application of this method to a clinical case. PMID- 8205060 TI - Titanium-porcelain system. Part I: Oxidation kinetics of nitrided pure titanium, simulated to porcelain firing process. AB - The bonding strength of porcelains to metals depends on the oxide layer between the porcelain and the metal. Oxidation of a metal surface increases the bonding strength, whereas excessive oxidation decreases it. Titanium and its alloys are gaining acceptance for dental use since they exhibit excellent biocompatibility, corrosion resistance, low specific gravity, good mechanical properties, and low cost. However, titanium suffers from its violent reactivity with oxygen at high temperatures that yields an excessive thick layer of TiO2, and this presents difficulties with porcelain bonding. The present study deals with the oxidation kinetics of titanium simulated to porcelain firing and evaluating surface nitridation of titanium as a process of controlling the oxidation behavior of titanium. Nitrided samples with the Arc Ion Plating PVD process and un-nitrided control commercially pure titanium (CPT, Grade 1) were subjected to oxidation simulating firing of Procera porcelain with 550 degrees, 700 degrees, and 800 degrees C firing temperatures for 10 min in both 1 and 0.1 atmospheric air. Weight difference before and after oxidation was calculated and the parabolic rate constant, Kp (mg2/cm4/s), was plotted against inverse absolute temperature. Surface layers of the samples were subjected to x-ray and electron diffraction techniques for phase identifications. Results revealed that both nitrided and un nitrided samples obey a parabolic rate law with activation energy of 50 kcal/mol. In addition this study shows that nitrided CPT had a Kp about 5 times lower than the un-nitrided CPT and hence the former needs about 2.24 times longer oxidation time to show the same degree of oxidation. Phase identification resulted in confirming the presence of TiO2 as the oxide film in both groups but with 1-2 microns thickness for the un-nitrided CPT and 0.3-0.5 micron thickness for the nitrided samples. Therefore it can be concluded that nitridation of titanium surface can be effective in controlling the surface oxide thickness that might ensure satisfactory bonding with porcelain. PMID- 8205061 TI - A new determination method of network chain-length distribution of rubber vulcanizates by chemorheology. AB - The structural changes of material caused by chemical reaction are reflected in the viscoelastic properties of these substances. Such a viscoelastic property induced by chemical reaction was termed chemorheology. Therefore, chemorheology is a relatively new discipline encompassing the physical and chemical aspects involved in the elucidation of the mechanisms, at a molecular level, of structural changes of polymers during their degradation. The studies presented here are the results stimulated further research in areas where this new determination will be more developed. PMID- 8205062 TI - The irradiation effect on the initial mechanical properties of meniscal grafts. AB - In this study, the effect of sterilization was investigated on the mechanical properties of rabbit's meniscal grafts. The processes of freezing and irradiation were carried out and their effects upon the elastic and viscoelastic properties measured using a tensile testing machine and an indentation test. It was found that gamma irradiation, at dosages commonly used for sterilizing grafts, had a significant adverse influence on the elastic and viscous response of the grafts. Freezing led also to a small significant decrease in elastic stiffness but no change in failure strength. It is concluded that irradiation sterilization is unsuitable for clinical use and other techniques should be used whenever possible. PMID- 8205063 TI - Diamond-like carbon as biological compatible material for cell culture and medical application. AB - Ion beam assisted diamond-like carbon (DLC) films have been used for growing the human hematopoietic myeloblastic ML-1 cells and human embryo kidney 293 cells in the control environment. DLC films were directly deposited onto the P-35 plastic dishes by impacting the high kinetic energy (1000 eV) of methane ions at room temperature. The present results showed that both ML-1 and HEK 293 cells continuously grow with and without DLC films. It has demonstrated that human cells proliferated on DLC film with very high viability and DLC material had no toxicity to cultured human ML-1 and HEK 293 cells. We conclude that DLC film is a biological compatible material for potential cell culture matrix and bio-medical applications. PMID- 8205064 TI - A novel skeletal drug delivery system using self-setting bioactive glass bone cement. IV: Cephalexin release from cement containing polymer-coated bulk powder. AB - A novel device consisting of Eudragit-coated cephalexin as a model drug and a self-setting bioactive cement based upon CaO-SiO2-P2O5 glass was investigated. The glass cement hardened within 5 min of mixing with a phosphate buffer. After setting, in vitro drug release from homogeneous or heterogeneous drug-loaded cement pellets in a simulated body fluid (SBF) at pH 7.25 and 37 degrees C continued for over 2 weeks. The hardened cement gradually formed low crystallinity hydroxyapatite and decreased in volume by about 5% during drug release in SBF. Consequently, 30% of the loaded drug was initially released from the homogeneous cement system, and thereafter it was released more slowly. Since the heterogeneous system consisting of the cement and a 50% polymer coated, drug loaded pellet avoided this drug's burst, the drug was released over a longer period than that in the homogeneous system. The heterogeneous system released the polymer-coated drug very slowly, because it completely avoided the initial burst, and sustained the release over a long period. PMID- 8205065 TI - Transcriptional and post-transcriptional regulation of protein synthesis. PMID- 8205066 TI - Insulin-like growth factor receptors: recent developments and new methodologies. PMID- 8205067 TI - DNA transfer. PMID- 8205068 TI - [Ap1-elements in the 5'-terminal region of the human apolipoprotein A-I gene, responsible for tissue-specific repression of this gene]. PMID- 8205069 TI - [Expression of human apolipoprotein A-I in mammalian cells, after recombinant retroviral transfer]. PMID- 8205070 TI - [Assessment of the energy status of rat brain upon frontal lobectomy; the protective effect of ganglioside GMI (NMR 31P in vivo)]. PMID- 8205071 TI - [Analysis of the character of large-scale fragmentation of Drosophila melanogaster DNA by topoisomerase II in vivo]. PMID- 8205072 TI - [Retrotransposon MDG4 (gypsy) integration hot spot and its precise excision from the D. melanogaster forked locus]. PMID- 8205073 TI - [New systems of locus-specific instability in Drosophila melanogaster, not dependent on P-M hybrid dysgenesis]. PMID- 8205074 TI - [Use of short retroposons as phylogenetic markers]. PMID- 8205075 TI - A behavioural approach to individually designed hearing tactics training. AB - In an experimental study involving 20 subjects functional consequences of hearing disability were assessed and counselled in accordance with behavioural principles. The aims were to develop psychological methods for analysing and relieving hearing problems. The results indicated that treated subjects improved significantly in three functional areas as compared to controls. Subjects also developed more knowledge and ability to handle hearing problems than controls. Although these findings suggest that behavioural methods can be beneficial in the understanding and rehabilitation of handicaps related to hearing disability, they must be interpreted with caution given the small sample size. PMID- 8205076 TI - Candidature for hearing aids: justification for the concept and a two-part audiometric criterion. AB - A definition of hearing aid candidature is required for planning and other purposes. The number of candidates in the population actually receiving an adequate fitting would provide the major index of whether audiology services achieve their major public health goal. Many diverse factors determine the benefit that an individual receives from a hearing aid, and hence could in principle be included in some composite criterion for appropriate candidature reflecting the cost-effectiveness of patterns of provision. However, the complexity of universal capture, on those fitted with hearing aids, of data giving full auditory and demographic characteristics is beyond current routine NHS information systems. The most powerful known determinant established to date both of auditory disability and benefit is average hearing threshold level (HTL). Hearing threshold levels are hence both a necessary part of the fitting process and, given the data from the National Study of Hearing, a sufficient basis for computing population prevalences of hearing characteristics and service uptake in the major demographic strata. We report epidemiological data on consultation about problems with ears or hearing and uptake of hearing aids, which lead us to recommend a two-part candidature criterion on hearing threshold levels (0.5-4.0 kHz average): EITHER (a) better ear HTL > or = 35 dB OR (b) (15 dB < or = better ear HTL < 35 dB) WHEN worse ear HTL > or = 45 dB. The asymmetric component (b) may appear contentious, but is directly supported both by the epidemiological data and by further clinical data on benefit measured as performance on speech-in noise tests. The proposed criterion is not over-liberal in clinical or related technological terms, but against the high prevalence of impairments in the population, the current provision and uptake of hearing aids in the UK still appear modest (about 3.3% in the population, and just under one-third of those qualifying by our criterion). Whatever the means of providing hearing aids, authorities charged with meeting the needs of their populations require such statistical indicators to know whether service delivery is appropriately geared. They should not use such an indicator as a basis of entitlement, as there are certainly individuals outside the criterion who receive benefit from their hearing aids. Equally, technological progress could expand the boundaries of candidature. PMID- 8205077 TI - External- and middle-ear factors affecting evoked otoacoustic emissions in neonates. AB - Babies without any of the known risk factors for hearing impairment were taken from normal maternity wards and tested daily for 3 days post-partum. Tympanometric and evoked otoacoustic emission data were obtained from 121 babies. Middle-ear pressure and middle-ear compliance values were obtained with a Grason Stadler Middle-Ear Analyser (GSI-33) using a 1000-Hz probe tone. All babies had their evoked emissions measured on the Programmable Otoacoustic Emissions Measurement System (POEMS) equipment. The middle-ear compliance, the proportion of normally shaped tympanograms, the middle-ear pressure and the proportion passing EOAE testing all improved over the 3 days. However, the statistically significant factors affecting the pass rate appeared to be only the middle-ear pressure (for a small number of babies) and the degree of obstruction of the external ear canal. Whilst both these factors play a part in determining emission pass/fail rates they do not fully account for the observed changes in pass rate. There are developmental and other mechanisms which must contribute to the increase in pass rate as the baby matures. PMID- 8205078 TI - Graft-versus-leukemia effect in allogeneic bone marrow transplantation in mice against several radiation-induced leukemias. AB - The intensity of graft-versus-leukemia (GVL) effect was studied using several radiation-induced leukemia cell lines (designated 8027, 8313, 9107, 7929) in MHC compatible and -incompatible allogeneic bone marrow transplantation (BMT) of leukemia-bearing C3H mice. The results indicated that BMT from MHC-incompatible allogeneic (B10, B10.D2) donors consistently improved the survival of the treated mice compared with that in syngeneic (C3H) donors. However, BMT from MHC compatible allogeneic (B10.BR, CBA, AKR) donors failed to improve the survival of 8027-bearing recipients. On the other hand, a remarkable improvement in survival of 8313, 9107 or 7929-bearing recipients was observed in MHC-compatible allogeneic (B10.BR, AKR) BMT but there was only a marginal GVL effect in MHC compatible BMT from CBA donors. There was no clear correlation between the intensity of GVL effect and the amount of class I MHC molecules expressed on leukemic cell lines. The activity of donor lymph node cells for the induction of lethal graft-versus-host disease (GVHD) correlated with the intensity of GVL effect induced by intact donor bone marrow. The results indicate that GVL effect against radiation-induced leukemias could be consistently induced in MHC incompatible allogeneic BMT whereas the intensity of GVL effect induced in MHC compatible allogeneic BMT varied among different leukemias and the donor-host strain combinations used. PMID- 8205079 TI - Interleukin-2 activation of human bone marrow in long-term cultures: an effective strategy for purging and generation of anti-tumor cytotoxic effectors. AB - Our previous studies have shown that IL-2 activated bone marrow cells develop potent tumoricidal activity in vitro and in vivo. With the dual aim of in vitro purging and generation of effectors which could mediate graft-versus-leukemia effects in vivo, IL-2 activation of human bone marrow in long-term cultures (LTC) was tested. Marked cytotoxicity was seen against A375 (melanoma), K562 (CML) and Daudi (lymphoma) cell lines in IL-2 (1000 U/ml) stimulated cultures. Hematopoietic progenitor cell number in these cultures was assessed by day 14 clonogenic assays. In 1-week-old IL-2 stimulated cultures a higher number of clonogenic cells was seen than control LTCs without IL-2. However, thereafter accelerated decrease in the number of clonogenic cells was seen in IL-2 cultures. In vitro purging efficacy was tested by elimination of A375 and K562 cells mixed with normal marrow at 1:10 and 1:100 ratios and co-cultured for 10 days. In IL-2 stimulated cultures, A375 cells capable of proliferation were not detectable at both mixing ratios. K562 elimination was complete only at 1:100 ratio. After 10 days in culture, no Ph1-positive metaphases were seen in IL-2 stimulated BM cultures of 4 patients with CML. These results indicate that IL-2 activation of BM in 1-2 week cultures can lead to generation of marked anti-tumor cytotoxicity and effective in vitro purging in a variety of tumor types. PMID- 8205080 TI - Effects of macrophage colony-stimulating factor (M-CSF) on the mobilization of peripheral blood stem cells. AB - We studied the effects of human urinary macrophage colony-stimulating factor (huM CSF) on the mobilization of peripheral blood stem cells (PBSC) following cytotoxic chemotherapy in 6 patients with acute leukemia. After complete remission (CR) was achieved, two courses of consolidation chemotherapy consisting of an intermediate dose of cytosine arabinoside were administered to the patients. During a recovery phase after each course of consolidation chemotherapy, two successive cycles of leukapheresis were performed every other day. M-CSF was administered intravenously at a dose of 8 x 10(6) U/day during a recovery phase after the second course of consolidation chemotherapy (cytotoxic plus M-CSF mobilization). There was no significant difference in white blood cell (WBC) or platelet recovery between the first and second cycles, regardless of the administration of M-CSF. Furthermore, between cytotoxic and cytotoxic/M-CSF mobilization, significant differences were not observed in the harvest of mononuclear cells (average 1.43 x 10(8)/kg vs 1.62 x 10(8)/kg), granulocyte/macrophage progenitor cells (CFU-GM) (1.82 x 10(4)/kg vs 3.07 x 10(4)/kg) or erythroid progenitor cells (BFU-E) (2.86 x 10(4)/kg vs 2.66 x 10(4)/kg). Thus M-CSF is not effective for expanding a pool of circulating hematopoietic stem cells when administered at a conventional dose during hematologic recovery following chemotherapy. PMID- 8205081 TI - Peripheral blood stem cell collection using the small volume collection chamber in the Fenwal CS-3000 Plus blood cell separator. AB - Optimal methods for peripheral blood stem cell (PBSC) collection should yield a small volume product containing minimal platelets and a large number of mononuclear cells (MNC). The Fenwal CS-3000 Plus blood cell separator was modified in an attempt to meet these objectives. Modifications of the CS-3000 Plus included use of the small volume collection chamber (SVCC), increasing the interface/offset detector setting to 150 and decreasing the centrifuge speed to 1400 rpm. Thirty-eight patients undergoing 224 PBSC collections were studied. Mobilization methods included 4 g/m2 cyclophosphamide (CY), CY + 250 micrograms/m2 subcutaneous granulocyte-macrophage colony-stimulating factor (GM CSF) or GM-CSF alone. The median collection volume was 58 ml containing a median of 21 ml of red blood cells. Platelet collection efficiency was < 4.4% and the median number of extracted platelets was 0.6 x 10(11)/apheresis. Median reduction in the platelet count post-apheresis was 15%. MNC purity was 95.5% and MNC collection efficiency was 61%. Yield of MNC was 1 x 10(8)/kg/apheresis. Collected progenitor cells correlated with both the WBC and MNC content of the apheresis product. The modified CS-3000 Plus with the SVCC is effective for PBSC collection following three different mobilization regimens and is, therefore, recommended for routine collection of PBSC. PMID- 8205082 TI - Collection, separation and cryopreservation of umbilical cord blood for use in transplantation. AB - Bone marrow transplantation (BMT) is limited by the paucity of HLA-matched donors and the frequent occurrence of graft-versus-host disease (GVHD). Recent clinical reports have implied that the use of umbilical cord blood (UCB) may alleviate some of the problems associated with BMT. Banks of frozen UCB could make the problem of finding suitable stem cell donors easier and stem cell grafts would be more readily available. However, definitive experiments are needed to develop optimal methods for collection, separation and storage of cryopreserved UCB for extended periods of time. We have found that several simple techniques may be utilized to collect large volumes of UCB (up to 220 ml). Also, modification of a common density gradient separation method permits recovery of large quantities of UCB mononuclear cells. Finally, we have examined the effects of prolonged frozen storage on the ability to recover viable and functional UCB, particularly stem/progenitor cells. It was observed that storage of UCB in liquid nitrogen for as long as 7 years had minimal effects on cell viability, cellular composition of UCB and progenitor/stem cell capacity. Thus, the establishment of UCB banks for use in transplantation appears to be a feasible approach. PMID- 8205083 TI - Effects of bone marrow transplantation on myocardial function in children. AB - Of 41 pediatric patients currently alive after total body irradiation (TBI) and bone marrow transplantation (BMT), 30 (allogeneic 20, autologous 10) participated in the study. Pre-transplant therapy included high-dose cyclophosphamide (CY) and TBI (n = 12), high-dose CY alone (n = 4), high-dose Ara C and TBI (n = 5), cisplatinum, high-dose melphalan, VP-16 and TBI (n = 9). Acute cardiotoxicity was suggested by a > 15% decrease in the QRS voltage sum of the limb leads in all patients. Late cardiotoxicity was evaluated 0.5-10 years (median 5 years) post transplant by ECG, chest radiograph, radionuclide cineangiography (RNCA) and echocardiography (ECHO). Six patients had a persistent decrease in the QRS amplitudes. They were all asymptomatic but had abnormal systolic function at the time of the study. BMT patients differed from their controls in the mean values of both the systolic and diastolic indices of myocardial function shown by RNCA and ECHO. Treatment was associated with decreased myocardial contractility. Isovolumic relaxation time and deceleration time were longer in BMT patients than in controls. Myocardial damage seemed to be worst after CY while high-dose Ara C was tolerated best. We conclude that both acute and late cardiotoxicity may occur after BMT, calling for long-term cardiac follow-up. PMID- 8205084 TI - Value of autologous bone marrow transplantation in follicular lymphoma: a France Autogreffe retrospective study of 42 patients. AB - The value of high-dose chemotherapy with hematologic stem cell rescue has not been established in the treatment of low-grade non-Hodgkin's lymphoma. We report the results of a retrospective 'France Autogreffe' study of 42 patients grafted in first partial remission (n = 13) or chemosensitive relapse (n = 29) for follicular lymphoma before January 1990. The median age was 38 years (range 26-61 years). Preparative therapy was chemotherapy alone in 22 patients and total body irradiation (TBI)-containing regimens in 20 patients. Thirty-seven patients received hematopoietic marrow stem cells. Bone marrow purging was performed in 15 patients. Five patients received peripheral blood stem cells. Three patients died of bone marrow transplantation toxicity and two others died in complete remission 10 months after autologous bone marrow transplantation. With a median follow-up of 43 months, relapse-free survival is 60%, event-free survival 58% and overall survival 83%. To date no prognostic factors have been shown. PMID- 8205085 TI - Efficacy of hyperimmune anti-cytomegalovirus immunoglobulins for the prevention of cytomegalovirus infection in recipients of allogeneic bone marrow transplantation: a meta-analysis. AB - We carried out an analysis of the randomized clinical trials published on the effectiveness of hyperimmune immunoglobulins for prevention of cytomegalovirus (CMV) infection or disease in CMV-seronegative recipients of allogeneic bone marrow transplantation (BMT). The clinical trials were identified by searching a number of computerized literature databases, by reviewing bibliographies of the paper examined and by consulting experts. All studies we selected were randomized and were aimed at evaluating the efficacy of hyperimmune immunoglobulins in comparison with a control group receiving no immunoglobulins. The results of this analysis indicate that hyperimmune immunoglobulins reduce the frequency of CMV infection (overall odds ratio = 0.444; 95% confidence interval 0.237-0.832, p = 0.011) and CMV related disease (overall odds ratio = 0.445; 95% confidence interval 0.223-0.887, p = 0.021) in CMV-seronegative recipients of allogeneic BMT. PMID- 8205086 TI - Ondansetron for efficient emesis control during total body irradiation. AB - Ondansetron is a 5-hydroxytryptamine receptor antagonist which has shown activity in the prevention of emesis following cytotoxic and radiation therapy for cancer. We describe our experience using ondansetron in 25 patients undergoing fractionated total body irradiation (TBI) 12 Gy/3 days as conditioning for bone marrow transplantation. Antiemetic efficiency was investigated during the 3 days of TBI prior to high-dose cytotoxic chemotherapy. Twenty-two of the 25 patients (88%) achieved sufficient emesis control with less than three emetic episodes whereas the remaining 12% experienced three to five emetic events during their worst 24-h period. Eleven patients (44%) had complete control with no vomiting at all. Of 75 'patient days', 52 (69%) were without any emesis, 20 (27%) were associated with one to two and only three (4%) with three to five emetic episodes. Headache occurred in four patients (16%). No other significant adverse effects were seen, in particular no extrapyramidal reactions due to ondansetron. Our data confirm that ondansetron plays a major role in the antiemetic management of patients undergoing TBI. PMID- 8205087 TI - Detection and significance of pulmonary Hodgkin's disease at autologous bone marrow transplantation. AB - Pulmonary Hodgkin's disease (HD) is considered to carry a poor prognosis both at presentation and at relapse. We have therefore studied the incidence and significance of pulmonary involvement in 190 poor risk HD patients undergoing BEAM therapy and ABMT for relapsed or resistant disease. Forty-one of 190 patients (22%) had clinically diagnosed pulmonary HD at some stage of their disease prior to ABMT. In 29 patients, in whom a full set of CT scans was available, the patterns of pulmonary HD were characterised. Four of 29 patients had pulmonary disease at presentation only, 8 of 29 at presentation and ABMT and 17 of 29 developed pulmonary involvement at relapse and proceeded to ABMT with persistent pulmonary disease. The commonest pulmonary abnormalities at presentation and relapse were discrete nodules (72%), masses extending from hilar or mediastinal nodes (34%) and pleural effusion/thickening (28%); 52% had two or more patterns of involvement and 66% had coexistent mediastinal lymphadenopathy. There was no relationship between pattern or bulk of pulmonary involvement and outcome. Consideration of the outcome following ABMT in all 190 patients revealed no significant difference in progression-free survival at 5 years between the pulmonary HD group (43%) and those without lung involvement (48%). Furthermore, there was no significant difference in complete remission or transplant-related death rates between the two groups. This would suggest that pulmonary involvement is not in itself a contraindication to ABMT and some patients with bulky pulmonary disease are capable of long-term survival. PMID- 8205088 TI - Constitutive and mitogen-stimulated cytokine mRNA expression by peripheral blood mononuclear cells from most autologous and allogeneic bone marrow transplant recipients is intact. AB - The immunodeficiency that occurs after human bone marrow transplantation (BMT) leaves BMT recipients susceptible to fatal infections. Although cytokines are critical for coordinating immune responses and immune reconstitution after BMT, there are still gaps in our knowledge about the expression of mRNA for cytokines in peripheral blood mononuclear cells (PBMC) after BMT. Therefore, we systematically studied cytokine gene expression by PBMC from 11 allogeneic and four autologous BMT recipients from 111 to 837 days after BMT and compared the results with PBMC from seven normal controls tested in parallel. PBMC were examined for mRNA expression for IL-2r alpha, IL-2, IL-3, IL-4, IL-6, and IL-7 using reverse transcription polymerase chain reaction (RT/PCR). PBMC from 11 allogeneic recipients constitutively expressed mRNA for IL-2r alpha in 2 of 11 and IL-2 in 1 of 9 samples tested whereas the same PBMC constitutively expressed mRNA for IL-3 in 8 of 11, IL-4 in 3 of 7, IL-6 in 6 of 7 and IL-7 in 3 of 6 samples tested. After PHA/PMA stimulation, PBMC from the same recipients frequently expressed mRNA for IL-2r alpha in 9 of 11, IL-2 in 8 of 9, IL-4 in 3 of 7 and IL-6 in 7 of 7. PBMC from four autologous recipients (two short-term and two long-term) frequently constitutively expressed mRNA for IL-2r alpha (3 of 4) IL-2 (3 of 4), and IL-3 (4 of 4). Stimulation of PBMC from the autologous recipients did not alter cytokine expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205089 TI - Allogeneic marrow transplantation in patients with chronic myeloid leukemia in chronic phase following preparation with busulfan and cyclophosphamide. AB - Thirty-four patients with chronic myelogenous leukemia in chronic phase were treated with busulfan 16 mg/kg and cyclophosphamide 120 or 200 mg/kg before allogeneic bone marrow transplantation from an HLA-identical sibling. Cyclosporine, methotrexate and prednisone were used for graft-versus-host disease (GVHD) prophylaxis. The actuarial probabilities of survival and relapse-free survival at 82 months were 71%. With a maximum follow-up of 2471 days, none of the patient experienced hematologic or clinical relapse. In one patient reappearance of host cells was documented 180 days post-transplant which disappeared 277 days post-transplant and the patient is in complete hematological and cytogenetic remission 5 years after the transplant. The probability of transplant-related mortality was 29% while the probability of moderate to severe acute graft-versus-host disease was 38%. This study indicates that busulfan and cyclophosphamide are a good conditioning regimen for marrow transplantation in patients with chronic myeloid leukemia in chronic phase. PMID- 8205090 TI - Effect of pentoxifylline on regimen related toxicity in patients undergoing allogeneic or autologous bone marrow transplantation. AB - An unblinded, historical controlled study of 49 bone marrow transplant (BMT) patients was carried out in our institution to assess the effect of oral pentoxifylline (PTX) on BMT regimen related toxicity (RRT). Twenty-eight consecutively treated BMT patients (17 allogeneic, 11 autologous) were entered into the PTX treatment group and treated with oral PTX 400 mg at intervals of 4 h from day -10 until day +35 or discharge, whichever came sooner. These were compared with a control group of 21 BMT patients (14 allogeneic, 7 autologous). Patient groups were very similar with respect to age, sex, conditioning regimen, graft-versus-host disease (GVHD) prophylaxis and baseline liver and renal function. Compliance with the drug was 85%. Despite this, no significant difference in days of mucositis or hyperalimentation, incidence or severity of renal or hepatic dysfunction, hypertension, GVHD, weight gain > 5%, day 100 mortality or length of hospitalization was observed. Median follow-up is > 2 years in both groups and no difference in relapse or survival was observed. We were unable to confirm an effect of oral PTX on BMT related morbidity or mortality. PMID- 8205091 TI - Cytomegalovirus interstitial pneumonia in autologous bone marrow transplant recipients. Infectious Disease Working Party of the European Group for Bone Marrow Transplantation. AB - CMV pneumonia is rare following ABMT. No information has been presented concerning risk factors or outcome of antiviral therapy. Information concerning CMV pneumonia after ABMT was collected from bone marrow transplant centers in Europe. Twenty-one patients who fulfilled the diagnostic criteria of CMV pneumonia were reported. Eighteen of these patients were reported from centers who also reported the total number of ABMT performed. The CMV pneumonia frequency among 2252 reported ABMT patients was 0.8%, and this varied from 0% to 8.6% between different centers. Survival for > 30 days from diagnosis of pneumonia was 43%. Three patients suffered relapses, which were fatal, giving a total survival of 28%. Patients treated with or without TBI had a survival of 18% and 50%, respectively. Among patients given ganciclovir or foscarnet with or without intravenous immune globulin, survival at 30 days was 50% and total survival 28%. There was no difference in survival with or without the addition of intravenous immune globulin. CMV pneumonia is an infrequent but serious complication of ABMT. PMID- 8205092 TI - Amebiasis after bone marrow transplantation. AB - A patient undergoing BMT for acute non-lymphocytic leukemia (ANLL) developed bloody diarrhea due to amebiasis. The infection was successfully treated with intensive and prolonged antiparasitic therapy. PMID- 8205093 TI - Seizure in a normal marrow donor: Addison's disease unmasked. AB - Adrenal insufficiency may be clinically occult yet cause life-threatening complications following even minor surgery. We report the case of a patient who became acutely hyponatremic after undergoing a marrow harvesting procedure using spinal anesthesia. The initial presentation mimicked the syndrome of inappropriate ADH (SIADH) secretion; however, further investigation revealed Addison's disease as the underlying cause. PMID- 8205094 TI - Molecular remission after allogeneic bone marrow transplantation for chronic lymphocytic leukemia. AB - A 51-year-old man with previously treated CLL received an allogeneic sex mismatched BMT after total body irradiation and high dose chemotherapy. Residual disease was studied at phenotypic and molecular levels including Y chromosome DNA amplification by PCR assay. The patient was clinically disease-free 20 months after BMT with disappearance of the leukemic clone assessed by the most sensitive methods of detection. Long-term follow-up is necessary to ascertain the relevance of Y DNA amplification in predicting outcome in this patient. PMID- 8205096 TI - Vogt-Koyanagi-Harada syndrome complicating allogeneic bone marrow transplantation. AB - Vogt-Koyanagi-Harada (VKH) syndrome is an uncommon acute ophthalmological disorder, characterised by bilateral serous retinal detachment with diffuse choroiditis, in association with specific extra-ocular manifestations. We describe a patient with unequivocal VKH syndrome arising 49 days after matched unrelated donor bone marrow transplantation (BMT) performed as treatment for severe aplastic anaemia. The visual symptoms and retinal changes responded well to corticosteroids. The haematological relevance of VKH syndrome is to distinguish it from retinitis due to cytomegalovirus, which requires different therapy and has a far worse visual prognosis. PMID- 8205095 TI - Bronchiolitis obliterans organizing pneumonia (BOOP) in children after allogeneic bone marrow transplantation. AB - Three pediatric patients of a cohort of 24 who underwent allogeneic bone marrow transplantation (BMT) from matched unrelated or mismatched family member donors developed low grade fever and cough between 2 and 3 months after BMT in the absence of clinical GVHD. Imaging studies revealed bilateral patchy opacities and open lung biopsies revealed the characteristic histological appearance of bronchiolitis obliterans organizing pneumonia. All three patients were treated with steroids and in two patients the syndrome resolved over 1-2 months; the third patient developed progressive pulmonary failure and died 2 weeks after diagnosis. BOOP may be an under-recognized respiratory complication following BMT from a matched unrelated donor or mismatched family member. PMID- 8205097 TI - High grade pyrexia following bone marrow transplantation as a neurotoxic complication of high-dose chemotherapy and radiotherapy in the UKALL XII Trial. PMID- 8205098 TI - Ganciclovir and the prevention of CMV disease after allogeneic BMT: policy at the Hammersmith Hospital. PMID- 8205111 TI - Identification of a previously unknown compound as 2'-deoxycytidine found in the plasma of breast cancer patients under combined chemotherapy. AB - In an attempt to find an end-point for cancer chemotherapy, this study was designed to measure the adenine compounds in the plasma of breast cancer patients using HPLC with a selective reagent for adenine bases. The patients were treated by chemotherapy using cyclophosphamide, methotrexate and 5-fluorouracil. Blood was collected in tubes containing EDTA, the plasma separated by centrifugation and analysed by HPLC. An early peak due to the fluorescent derivative of an unknown compound reacted with bromoacetoaldehyde and its concentration appeared proportional to the chemotherapeutic courses of treatment. The compound in its native state without fluorescent derivatization was efficiently purified by using columns of DEAE- and CM-Sephadex. Its UV spectrum revealed maxima at 271, 280 and 272 nm in solutions of pH 7, pH 3 and pH 12, respectively. The electrophoretograms showed that it was neutral, positively and negatively charged at pH 7, pH 3 and pH 12, respectively. Thin-layer chromatograms showed that it had the same Rf as 2'-deoxycytidine (dCyd) which was confirmed by a positive reaction for deoxyribose. It was concluded that bromoacetoaldehyde formed a weakly fluorescent product with dCyd which gave rise to the early peak in the anion exchange chromatograms. From the calculation of the recovery obtained by the purification process, the cancer patients undertaking more than 12 courses had a dCyd level of approximately 20 mM while the corresponding figure in normal volunteers was less than 1 mM. These results may be useful in assessing the status of the cancer patients. PMID- 8205112 TI - An improved method for the purification of human erythropoietin with high in vivo activity from the urine of anemic patients. AB - An improved method for the purification of human erythropoietin with high in vivo activity from urine was developed. This method involved ion-exchange, gel permeation, affinity chromatography, and reverse-phase chromatography but did not involve any stabilizing procedures. The purified human urinary erythropoietin showed a single broad band with a molecular weight between 37000 and 39000 Da on sodium dodecyl sulfate polyacrylamide gel electrophoresis, and had an in vivo specific activity of 160000 IU/mg comparable to that of human erythropoietin produced in recombinant Chinese hamster ovary cells. We found that omission of the phenol treatment and ethanol precipitation which are usually used in the purification of human urinary erythropoietin greatly improved the biological activity of the final product. Phenol treatment followed by ethanol precipitation did not affect the amino acid composition but decreased the apparent molecular weight and N-acetylglucosamine content of human urinary erythropoietin. These findings suggest that phenol treatment followed by ethanol precipitation does not restore erythropoietin with high branched sugar chains which would have high in vivo specific activity as reported previously (M. Takeuchi, et al. (1989) Proc. Natl. Acad. Sci. U.S.A., 86, 7819-7822). PMID- 8205113 TI - Properties of three proteinases functioning at G1, S and G2 phases in HeLa cells and their inhibition by guanidino- and amidino-acid esters. AB - HeLa cells were synchronized by double thymidine-block and allowed to grow after removal of thymidine. Three proteinases, tryptase 17:17, proteinase In and late G2 proteinase, were prepared from the HeLa cells harvested at the time when each proteinase appeared in the cell cycle of the cells. All of them were suggested to be trypsin-like serine proteinases, because they hydrolyzed trypsin-specific fluorogenic substrates and their activities were inhibited by benzamidine, soybean trypsin inhibitor, leupeptin, tosyl-L-lysine chloromethan (TLCK) and diisopropylfluorophosphate (DEP). However, the actions of these proteinases on the substrates and inhibitors suggested that they were three different proteinases. They were strongly inhibited by 4-tert-butylphenyl and biphenyl esters of trans-4-guanidinomethylcyclohexanecarboxylic acid, amidinopiperidine-4 acetic and 4-propionic acids, which retard the second DNA synthetic (S) and mitotic (M) phases for 3h, 4-tert-butylphenyl ester of amidinopiperidin-4 carboxylic acid, which blocks initiation of S phase, the ester of amidinopiperidine-4-butyric acid, which suppresses the second S and M phases, and the esters of trans-4-amidinocyclohexanecarboxylic and 4-propionic acids which inhibit M phase. PMID- 8205114 TI - Stabilization and enhanced enzymatic activities of a mutant human lysozyme C77/95A with a cavity space by amino acid substitution. AB - Amino acid substitutions were examined to increase the stability of the mutant human lysozyme C77/95A by filling the cavity created by this mutation. To modulate the cavity with hydrophobic amino acids or by the formation of a hydrogen bond, five amino acid-substituted mutants, C77AC95L, C77AC95I, C77LC95A, C77IC95A and C77/95S, were designed and constructed based on computer graphics investigations for stabilizing the mutant protein. The values of the melting temperatures, Tm, at pH 3.0 of the two mutant proteins C77LC95A and C77/95S were increased by 2.9 degrees C and 2.3 degrees C, respectively, as compared to that of C77/95A. The C77IC95A and C77AC95L proteins showed almost the same stability as C77/95A. The increase in the stability of the proteins might be explained by the filling of the cavity space around positions 77 and 95 with the side residue of Leu77 in C77LC95A, and by the formation of a hydrogen bond between Ser77 and Ser95 in C77/95S. On the other hand, the substitution with isoleucine at 95 (C77AC95I) decreased the stability. The activities of the five mutant proteins against the synthetic substrate, p-nitrophenyl tetra-N-acetyl-beta chitopentaoside, were higher than that of the wild-type human lysozyme, while the lytic activities against M. lysodeikticus were decreased in C77LC95A and C77IC95A, and increased in C77AC95L. PMID- 8205115 TI - Pharmacological activity of chemically modified subfragment from human serum IgG. XI. Increment of tumor necrosis factor (TNF) activity in mouse sera by carboxamide-methylated light chain. AB - Intravenous administration of the carboxamide-methylated light chain (G1L) from human serum IgG induced tumor necrosis factor (TNF), one of the inflammatory cytokines, in the serum of mice. Human serum IgG, however, showed no induction of TNF in the serum. G1L showed a potent anti-inflammatory effect in carrageenin induced paw edema, and the anti-inflammatory effect of G1L was significantly blocked by the concomitant administration of anti-TNF antiserum, but TNF alone had no anti-inflammatory effect. PMID- 8205116 TI - Nephrotoxicity induced by a single dose of adenine: effects of 4 aminopyrazolo[3,4-d]pyrimidine and allopurinol. AB - The effects of allopurinol and 4-aminopyrazolo[3,4-d]pyrimidine (4APP) on adenine induced renal injury in mice were examined. Plasma urea nitrogen (UN) and creatinine levels increased after the oral administration of adenine to mice. However, plasma UN and creatinine levels decreased inversely with the dose of 4APP when a different dosage of 4APP was administered together with adenine. Yet 4APP did not have any effect on the UN or creatinine levels when 4APP was administered after adenine administration. Plasma UN and creatinine levels increased in the allopurinol-administered group as in the adenine-administered group. Moreover, from light microscopic observation by hematoxylin-eosin staining, microvacuolic changes in the proximal tubuli were detected in the mouse kidney in the adenine-administered group, and epithelial cell loss, degeneration and microvacuolic changes in the proximal tubuli were observed in the mouse kidney in the adenine-and-allopurinol-administered group. However, there were no changes in the proximal tubuli in the mouse kidney in the adenine-and-4APP administered group. These findings suggested that 4APP inhibits the action of adenine in the mouse kidney. PMID- 8205117 TI - Inhibitory activities of metal chelators on endothelin-converting enzyme. I. In vitro studies. AB - The effects of various metal chelators on endothelin (ET)-converting enzyme (ECE) activity were examined in vitro. Three chelators, 2,3-dimercapto-1-propanol (DMP), toluene-3,4-dithiol (TDT) and 8-mercaptoquinoline (8-MQ), were found to dose-dependently inhibit ECE activity, but this inhibition was much weaker compared with EDTA. In the presence of Zn2+, the inhibitory activity of all these compounds, including EDTA, was abolished. The addition of Ca2+ and Mg2+ markedly attenuated the inhibitory activity of EDTA, but the other three chelators were still able to inhibit ECE. ECE, once inactivated by EDTA or 8-MQ, was reactivated by the addition of divalent cations such as Zn2+ and Mn2+. These compounds also inhibited angiotensin-converting enzyme activity in a manner similar to the inhibition exhibited towards ECE. Chelate-titration indicated that DMP, TDT and 8 MQ chelate Zn2+ but not Ca2+ and Mg2+. These results suggest that the ECE inhibition exhibited by these compounds is mainly attributable to their chelating activities. The metal-selective chelating activity by DMP, TDT and 8-MQ may contribute to the retention of ECE inhibition in the presence of Ca2+ and Mg2+. PMID- 8205118 TI - Inhibitory activities of metal chelators on endothelin-converting enzyme. II. In vivo studies. AB - The effects of metal chelators on endothelin (ET)-converting enzyme (ECE) activity in vivo were examined. Three compounds, (2,3-dimercapto-1-propanol (DMP), toluene-3,4-dithiol (TDT) and 8-mercaptoquinoline (8-MQ)), which inhibited ECE in in vitro studies, exhibited inhibitory activity towards big ET-1-induced sudden death in mice, while EDTA did not. Similar results were obtained in big ET 1-induced hypertension. Big ET-1-induced hemoconcentration was inhibited by pretreatment with 8-MQ or EDTA but not with DMP or TDT. The elevation of immunoreactive ET-1 (IR-ET-1) in plasma after administration of big ET-1 was inhibited by pretreatment with the three compounds but not by EDTA. On the other hand, no chelator inhibited the elevation of IR-ET-1 in lung tissue after injection of big ET-1. Taking into consideration the in vitro results, more selective chelating activity of the compounds towards Zn2+ rather than Ca2+ and Mg2+ may contribute to the inhibition of big ET-1-induced responses in vivo. The ET-1 formation involved in big ET-1-induced hemoconcentration may have different physiological characteristics from that involved in big ET-1-induced sudden death or hypertension. PMID- 8205119 TI - Effects of Crocus sativus L. on the ethanol-induced impairment of passive avoidance performances in mice. AB - The acute effects of an alcohol extract of Crocus sativus L. (CS-extract) were studied on learning and memory in step through (ST) and step down (SD) tests in normal as well as in learning- and memory-impaired mice. A single oral administration of CS-extract had no effects on memory registration, consolidation or retrieval in normal mice. CS-Extract reduced the ethanol-induced impairment of memory registration both in ST and SD tests and the ethanol-induced impairment of memory retrieval in SD test. CS-Extract decreased the motor activity (MA) and prolonged the sleeping time induced by hexobarbital. These results suggested that CS-extract ameliorates the impairment effects of ethanol on learning and memory processes, and possesses a sedative effect. PMID- 8205120 TI - Differential induction of chromosomal aberrations by topoisomerase inhibitors in cultured Chinese hamster cells. AB - The inducibility of chromosomal aberration was studied using five mammalian topoisomerase inhibitors in Chinese hamster lung fibroblastic cells (CHL) in two protocols involving 6 and 24 h treatment, with respect to the mechanism of chromosomal aberration. In the 6 h treatment plus 18 h recovery culture (6 h treatment), a high incidence of chromosome-type aberration was observed with three mammalian topoisomerase II (topo-II) inhibitors: etoposide, adriamycin and mitoxantrone, which stabilize the cleavable complex of topo-II and DNA. In the 24 h continuous treatment (24 h treatment), these chemicals induced mainly chromatid type aberrations. The chromosome-type aberrations which appeared as a result of the 6 h treatment were primarily induced, because the majority of aberrant cells induced by the inhibitors remained in the first metaphase, as determined by the 5 bromodeoxyuridine labelling method. This also indicates that the cells were sensitive to these topo-II inhibitors at the G1-S boundary phase. Aclarubicin, however, which does not form the cleavable complex but is an antagonist against topo-II, and camptothecin, an inhibitor of topoisomerase I, mainly induced chromatid-type aberrations, irrespective of the duration of treatment. These results suggest that the differential induction of chromosomal aberrations by topoisomerase inhibitors reflects different mechanisms of inhibition by the topoisomerases, and that DNA double strand breakages promoted by the stabilization of the cleavable complex formed by topo-II are closely associated with the induction of chromosome-type aberration. PMID- 8205121 TI - A role of iron in lambda DNA strand breaks in the reaction system of alloxan with reduced glutathione: iron(III) binding to the DNA. AB - lambda DNA strand breaks were easily induced in a reaction system involving alloxan with reduced glutathione (GSH) in the presence of FeCl3 in a HEPES-NaOH buffer, pH 7.4. Increasing concentrations of FeCl3 in the reaction system caused DNA strand breaks in a concentration-dependent fashion, suggesting that iron is required to induce the DNA strand breaks. Catalase, scavengers of hydroxyl radicals (HO.) and iron-chelators almost completely inhibited the DNA strand breaks, but superoxide dismutase (SOD) did not do so, suggesting that the HO., formed by a Fenton-type reaction, was the species responsible for the DNA strand breaks. The addition of FeCl3 to the solution containing DNA caused the formation of a DNA-Fe(III) complex, in which Fe(III) was reduced by an alloxan radical (HA.) but not by a superoxide radical. Only when apotransferrin was added to the reaction mixtures before the addition of FeCl3, were both the DNA strand breaks and the reduction of Fe(III) strongly inhibited. These results suggest that the Fe(III) bound to DNA catalyzes the DNA strand breaks which may be caused by the generation of site-specific HO. via an HA.-dependent Fenton-type reaction. PMID- 8205122 TI - Defense effects of a traditional Chinese medicine (sho-saiko-to) against metabolic disorders during endotoxemia; approached from the behavior of the calcium ion. AB - The present study was carried out as an approach from intracellular Ca2+ to clarify the preventive effects of a traditional Chinese medicine, Sho-saiko-to (Kampo prescription, TJ-9), against various metabolic disorders during endotoxemia. In this experiment, we estimated the cytosolic-free Ca2+ concentration ([Ca2+]i) in liver single cells using a photonic microscope system. The [Ca2+]i in a single liver cell of endotoxin (6 mg/kg, i.p.)-injected mice was greater at 18 h post-intoxication than that in the control, whereas the administration of endotoxinin to TJ-9 (500 mg/kg/d, p.o.)-pretreated mice resulted in a markedly lower level of [Ca2+]i than that in endotoxin-treated mice. In the mice pretreated with TJ-9, the CA(2+)-ATPase activity in liver plasma membrane 18 h after endotoxin injection was markedly increased as compared to that in the endotoxin-treated mice. By contrast, the Ca(2+)-ATPase activity in liver mitochondria was lower in endotoxemic mice pretreated with TJ-9 than in mice given endotoxin alone. State 3 respiration and the respiratory control index (RCI), which are the parameters of mitochondrial function, were 41% and 35% lower, respectively, in the liver of mice given endotoxin than those levels in the control. However, the levels of state 3 and RCI in endotoxin-TJ-9-treated mice were markedly increased as compared to those of the endotoxin-treated mice. These findings suggest the protective effect of TJ-9 in the damage of liver mitochondrial function in endotoxin-poisoned mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205124 TI - Comparison of the effects of ioversol and other contrast media on the blood-brain barrier. AB - Little information is available concerning the neurotoxicity of ioversol injected in animals. The effects of ioversol and other contrast media as well as vehicle control on the blood-brain barrier (BBB) were examined by injection into the left carotid artery of Mongolian gerbils 1 min prior to the i.v. injection of [8 14C]dopamine. The animals were sacrificed 1 min after the i.v. injection to prepare the frontal brain sections following the stereotaxic atlas. No uptake of the labeled substance was observed when the vehicle control and ioversol were used, suggesting that exposure to ioversol does not damage the BBB. Both meglumine sodium amidotrizoate and iohexol caused damage to the BBB, as shown in the cerebral cortex, brain stem, and hippocampus sections in the left semisphere. Iopaidol induced a much less but significant effect. Our results suggest that ioversol is an useful contrast medium. PMID- 8205123 TI - Protective effects of hydroxychalcones on free radical-induced cell damage. AB - A number of hydroxychalcones were synthesized to evaluate their protective effects against oxidative cell damage and the production of superoxide anion. The hydroxychalcones which have a 3,4-dihydroxycinnamoyl structure were potent inhibitors of lipid peroxidation in rat liver microsomes. In particular, we found that 2',4',3,4-tetrahydroxychalcone (3) exhibited a potent inhibitory effect on H2O2-induced hemolysis due to an antioxidant effect. In addition, this compound strongly inhibited CCl4-induced cytotoxicity in primary cultured hepatocytes and substantially decreased the production of superoxide anion by rat peritoneal exudate macrophages. PMID- 8205125 TI - Tyrosinase inhibitors from crude drugs. AB - Various crude drugs were examined for their tyrosinase inhibitory activity. Marked activity was observed in Chouji and Yakuchi extracts and the active substances in these extracts were identified as eugenol and yakuchinone A, respectively. Other vanillyl compounds such as ferulic acid, curcumin and yakuchinone B also had higher activities than eugenol or yakuchinone A and inhibited the enzyme competitively. The presence of the hydroxyl group at the 4 position of the aromatic ring of the cinnamoyl moiety and the alpha,beta unsaturated carbonyl conjugated with an aromatic ring in these substances may play important roles in the competitive inhibition of tyrosinase. PMID- 8205126 TI - Protective effect of ginseng saponins against impaired brain growth in neonatal rats exposed to ethanol. AB - This study was performed to determine the active constituents of the root of Panax ginseng C. A. Mayer in the amelioration of ethanol-induced impediment of brain growth in the neonatal stage. To establish an animal model of the brain growth impediment caused by ethanol, ethanol (6 g/kg s.c.) was administered to rat pups on postnatal day 6, which corresponded to the third trimester of pregnancy for humans. Brain weight, especially cerebellar weight, was significantly reduced in the ethanol-exposed pups. In contrast, neither separation from dams nor pentobarbital treatment affected brain weight. A saponin fraction of ginseng extract prevented this ethanol-induced reduction of brain weight. Some ginseng saponins including ginsenosides Rg1, Rb2, Rd, Rf and Re effected stimulated a potent recovery of cerebellum growth in this animal model. PMID- 8205127 TI - Tissue-targeting ability of saccharide-poly(L-lysine) conjugates. AB - To evaluate the effect of introducing a saccharide moiety to poly(amino acids) on tissue distribution, several glycoconjugates of epsilon-(2-methoxyethoxyacetyl) poly(L-lysine) of three molecular weights were synthesized using an octylene spacer between the sugar and polymer chain. Methoxyethoxyacetylation of the epsilon-amino group of the lysine unit in poly(L-lysine) was useful for avoiding nonspecific distribution to many tissues as the result of cationic charges. The tissue-targeting ability of each saccharide moiety was considered as the actual amount changed in each tissue caused by saccharide modification. Galactose terminated saccharides such as galactose, lactose and N-acetylgalactosamine accumulated exclusively in the liver, probably by the hepatic receptor. These conjugates could therefore be good carriers for a drug delivery system to the liver. On the other hand, the mannosyl and fucosyl conjugates were preferentially delivered to the reticuloendothelial systems such as those in the liver, spleen and bone marrow. In particular, fucosyl conjugates accumulated more in the bone marrow than in the spleen. Xylosyl conjugates accumulated mostly in the liver and lung. Generally, the accumulated amount in the target tissue increased with increasing molecular weight and an increased number of saccharides on one molecule of polymer. PMID- 8205128 TI - In vivo/in vitro correlation of intravitreal delivery of drugs with the help of computer simulation. AB - The elimination of dexamethasone sodium m-sulfobenzoate, DMSB, following intravitreal injection, was measured in rabbit vitreous body under in vivo and in vitro conditions. The rate of elimination in vivo was appreciably greater than that in vitro, indicating that the in vivo data include not only the elimination due to metabolism/degradation in the vitreous humor, but also the elimination through the surrounding tissues such as the posterior aqueous humor, the retina/choroid/sclera membrane, and the lens. A general mathematical model based on Fick's second law of diffusion was developed for describing the pharmacokinetics of the intravitreal injection of DMSB. The model parameters were independently determined from a set of in vitro experiments. The in vivo data of elimination of DMSB following intravitreal injection agreed with the profiles calculated from the mathematical model, together with the model parameters determined from the in vitro experiments. The present in vivo/in vitro correlation, with the help of computer simulation, can be used for optimizing the therapeutic systems of intravitreal drug delivery. PMID- 8205129 TI - Evaluation of the correlation between in vivo and in vitro release. Effect of the force of contraction and food on drug release. AB - The effects of the force of contraction in the gastrointestinal (GI) tract and of food on drug release were investigated. Two dosage forms were administered orally to beagle dogs. Dosage form A was a matrix in which drug release was affected by the force of contraction in the GI tract, and dosage form B was not affected by the contraction force. The in vitro dissolution curves from dosage forms A and b using the paddle-beads method were similar to in vivo drug release, with the respective release of up to at least 50%. The in vitro release by means of the paddle-beads method was characterized by the in vivo drug release. The in vivo drug release profile from dosage form A was affected by food. A 1:1 relationship between in vivo and in vitro release was observed up to 6 h in those dogs under the fed condition, but only up to 2.5 h in those under the fasted condition. In the earlier stage of oral administration there was no difference in drug release profile between dogs of the fed and fasted conditions; however, the drug release rate in the fed condition was faster than that in the fasted condition 2-4 h after administration. It was thus assumed that in the fed condition, drug release from dosage form A was affected by gastro-duodenal transit time or by the different environment in the distal parts of the GI tract rather than by the force of contraction. PMID- 8205130 TI - Rectal absorption of ozagrel from suppositories in rabbits. AB - Rectal absorption of ozagrel (a selective thromboxane synthetase inhibitor) from suppositories was studied in rabbits. Two kinds of suppositories were prepared, one was from ozagrel powder (OPS, ozagrel powder suppository), and the other from ozagrel tablet (OTS, ozagrel tablet suppository). Ozagrel from OPS was absorbed quickly with a Tmax value of 26.3 +/- 7.5 min, and the peak plasma level was significantly higher than that involving intravenous infusion or oral dose (50.3 +/- 6.7 vs. 32.8 +/- 5.4 or 9.9 +/- 1.2 micrograms/ml), indicating that OPS may be a useful dosage form rather than injection. OTS was absorbed less rapidly than OPS, but the AUCs of both suppositories were similar. Because OTS was prepared using an ozagrel tablet, it is fairly easy to get an equal content in each suppository. Therefore, OTS is not only an experimentally interesting dosage form, like OPS, but is also a practical preparation for clinical use. PMID- 8205131 TI - Non-congeneric structure-pharmacokinetic property correlation studies using fuzzy adaptive least-squares: oral bioavailability. AB - Quantitative relationship between chemical structure and oral bioavailability of 188 non-congeneric organic medicinals were studied to construct an expert system for predicting pharmacokinetic properties of organic chemicals. The compounds studied were classified into three groups: non-aromatics, aromatics, and heteroaromatics. Their oral bioavailability data observed in human adults were allotted into three ratings, and the relationships with chemical structure were analyzed using fuzzy adaptive least-squares. Quantitative relationship models formulated for the three structure groups gave significant information about factors influencing bioavailability, and were statistically reliable in both recognition and leave-one-out prediction despite the diversity and complexity of the structures of the compounds investigated. PMID- 8205132 TI - Population analysis of the dose-dependent pharmacokinetics of zonisamide in epileptic patients. AB - The pharmacokinetics of zonisamide was studied using routine therapeutic drug monitoring data from 68 epileptic patients. The 266 serum concentration data at steady-state after repetitive oral administration were analyzed using the nonlinear mixed effects model (NONMEM) program designed for estimation of population pharmacokinetic parameters. A one-compartment model with dose dependent clearance was used for the pharmacokinetic analysis of zonisamide. The volume of distribution (V) was estimated to be 1.27 l/kg in a typical 33-kg patient, assuming that the bioavailability of orally administered zonisamide is 100%. The maximal daily dose to be cleared (Vmax) and the concentration giving half maximal clearance (a Michaelis-Menten constant) was 27.6 mg/d/kg and 45.9 micrograms/ml, respectively. The parameter of a power function of weight to adjust V and Vmax was estimated to be 0.741. In addition, Vmax for zonisamide appears to be 13% increased in patients receiving carbamazepine concurrently. The population pharmacokinetic parameters of zonisamide will be useful for designing dosage regimens in epileptic patients. PMID- 8205133 TI - Drug absorption from large intestine: physicochemical factors governing drug absorption. AB - Profiles of absorption versus drug molecular weight and absorption versus drug lipophilicity were investigated in both the small and large intestines of rats by an in situ loop method. The absorption-molecular weight profiles examined using different-sized polyethylene glycols (PEGs) were different between the small and large intestines; the large-intestinal absorption of PEGs with molecular weights larger than 300 was poor, while PEGs with molecular weights up to 600 were relatively well absorbed in the small intestine. It is suggested that the paracellular route for drug penetration in the large intestine is restricted more than in the small intestine. The absorption-lipophilicity profiles were also examined in various regions (loops of 6 cm) of rat intestine using three acylsalicylic acids, acetyl-, propionyl- and butyrylsalicylic acids. The absorption rates of the acylsalicylic acids were different in the intestinal regions: the jejunum > the ileum > the colon > the rectum. In each region, the absorption rate increased with the drug lipophilicity. However, it was shown that the absorption rates in the small intestine tended to reach a ceiling at the high lipophilicity. To confirm this tendency, the absorption rates of acetaminophen and indomethacin were compared in the four intestinal regions. The absorption rates of highly lipophilic indomethacin were similar in the large and small intestines, while intermediately lipophilic acetaminophen was more rapidly absorbed in the small intestine than in the large intestine. A thicker unstirred water layer adjacent to the small-intestinal mucosa would be one of the factors which cause such varying absorption-lipophilicity profiles. PMID- 8205134 TI - Development of radioimmunoassay for the novel platelet activating factor receptor antagonist, E6123, and its application to pharmacokinetics in laboratory animals. AB - A direct radioimmunoassay for the determination of E6123, a novel antagonist of platelet activating factor (PAF) receptor, was developed in order to study the pharmacokinetics at low dose. This procedure used [3H]E6123 as the radioligand and an antiserum obtained from rabbits immunized with the hapten covalently bound to bovine serum albumin. M1B, one of the main metabolites of E6123, exhibited cross-reactivity with antisera. But this metabolite had no effect on measurements of E6123, because the amount of M1B in plasma radioactivity after administration of [14C]E6123 to dogs and monkeys was low. The sensitivity limit of this assay was 25 pg/ml of plasma when 0.1 ml of plasma was used and the assay showed good accuracy and high precision. The validity of the radioimmunoassay was demonstrated by comparative analysis of a number of samples after oral and intravenous administration (1.0 mg/kg) by HPLC-UV method (r = 0.972-0.984, slope = 1.0314-1.2143). The pharmacokinetics of E6123 was studied at a dose of 30 micrograms/kg. After intravenous administration, the plasma concentration-time curves in all species fitted a two-compartment model and the terminal half-lives in guinea pigs, dogs and monkeys (both poor and extensive metabolizers) were 4.77, 1.71, 5.34 and 1.07 h, respectively. After oral administration, the maximum plasma concentrations were obtained within 0.83-3.00 h and the half-life for each animal was almost the same as that after intravenous administration. The mean bioavailabilities of E6123 in guinea pigs, dogs and monkeys (poor and extensive metabolizers) were 106.9, 45.7, 59.1 and 22.8%, respectively. PMID- 8205135 TI - Analysis of the transport of valproic acid into saliva from serum. AB - A study was conducted to explore whether a positive correlation between serum and salivary concentrations of the well-known antiepileptic drug, valproic acid (VPA), in epileptic patients could be explained by facilitated diffusion. The total concentration in saliva (Cs) would be related to the apparent ratio (R(app)++ = 100.Cs/Ct) of Cs to the total concentration in serum (Ct) as follows: Cs = A.R(app)B. This equation can be illustrated with microcomputer-simulated figures by assuming a process of facilitated diffusion for the transport of VPA into saliva from blood by the mechanism of monocarboxylic acid absorption through the intestinal brush-border membrane vesicles. The above equation has been proved to be valid when applied to the data reported separately by Gugler and coworkers and by Nitsche and Mascher, who evaluated the pharmacokinetics of VPA. Moreover, we can estimate the serum concentration with the salivary concentration using the above equation. PMID- 8205136 TI - Stimulatory effect of beta-alanyl-L-histidinato zinc on alkaline phosphatase activity in bone tissues from elderly rats: comparison with zinc sulfate action. AB - The capability of beta-alanyl-L-histidinato zinc (AHZ) to increase alkaline phosphatase activity in the femoral diaphysis from elderly rats was investigated. The femoral-diaphyseal tissues were removed from weanling (3-week-old) and elderly (10-month-old) female rats. Bone tissues were cultured in Dulbecco's modified Eagle medium (high glucose, 4.5%) supplemented with antibiotics and bovine serum albumin. Among various other bone-stimulating factors (AHZ; 10(-5) M, zinc sulfate; 10(-4) M, sodium fluoride; 10(-3) M, insulin; 10(-8) M, and beta estradiol; 10(-9) M), AHZ had a potent effect on increasing alkaline phosphatase activity in the diaphyseal tissues from both rat groups. In the bone tissues from elderly rats, the effect was concentration dependent (10(-7) - 10(-5) M). At 10( 5) M the effect of AHZ was seen for a longer time during 72-h culture, although the zinc sulfate (10(-5) M) effect was no longer. The effect of AHZ to increase bone alkaline phosphatase activity was completely abolished by the presence of cycloheximide (10(-6) M). AHZ thus appears able to directly stimulate alkaline phosphatase activity dependent on protein synthesis in the bone tissues from elderly rats. PMID- 8205137 TI - Age-dependent decreases in fibrinolytic enzyme activities in serum of healthy subjects. AB - We investigated the age-dependency of serum levels of 9 kinds of proteases. The results showed that the enzymatic activities corresponding to urokinase, plasmin, and thrombin, all involved in blood clotting and fibrinolysis, were inversely correlated with age. This suggests that there is some similarity between the normal process of aging and the pathologic process of Alzheimer's disease. Compared with our previous data on Alzheimer patients, the present results indicate that some derangement in the aging process is involved in the pathogenetic mechanisms of Alzheimer's disease. PMID- 8205138 TI - Expression in Escherichia coli of a TetK determinant from Staphylococcus aureus. AB - The expression in Escherichia coli of a tet(K) gene, which originated in Staphylococcus aureus, was studied. The minimum inhibitory concentration (MIC) of tetracycline (TC) for E. coli cells that carried the tet(K) gene was only slightly higher than that for the recipient cells. This result indicated that the level of expression of the tet(K) gene in E. coli was very low. Insertion of a lac promoter into the upstream region of the tet(K) gene resulted in a slight increase in the MIC, from 12.5 to 50 micrograms/ml in the presence of isopropyl beta-D-thiogalactopyronoside. An altered tet(K) gene, in which the initiation codon and the ribosome-binding site (RBS) were changed from TTG to ATG and from GAGG to GGAGG, respectively, and in which the distance between the RBS and the initiation codon was increased from 4 to 11 bases, was associated with high-level resistance to TC, with a MIC of 200 micrograms/ml. The MIC resembles that associated with expression of the tetA(B) gene of E. coli. These results indicate that the barrier to expression of the tet(K) gene in E. coli is located at the initiation of translation. PMID- 8205139 TI - Inter-organ relation between salivary gland and kidney in lithium excretion. IV. Saturation of inhibitory effect of NaCl on ductal reabsorption of Li+ in beagle dogs. AB - The inhibitory effect of NaCl coadministration on the reabsorption of Li+ in the salivary ducts and the renal tubules was investigated in beagle dogs. Following the bolus intravenous administration of LiCl (0.145 meq/kg), 50 ml of NaCl solution (100, 200 meq/l) was administered orally each hour, and parotid saliva (Pr) and mandibular-sublingual saliva (MS) were collected under the continuous stimulation of salivation with citric acid. The renal clearance of Li+ increased with the increased concentration of administered NaCl solution. This could be a result of the competitive inhibition of the tubular reabsorption of Li+ by Na+. The salivary clearance of Li+ also tended to increase by the administration of NaCl. These results suggest the existence of a reabsorption process of Li+ in the salivary glands similar to that in the renal tubule. However, when the administered NaCl was increased from 100 to 200 meq/l, the renal clearance was further increased, but the salivary clearance was not. This suggests that the transport capacity of Li+ reabsorption is relatively small in the salivary glands, compared with that in the renal tubule, and that the inhibitory effect of NaCl on Li+ reabsorption had already reached a maximum level when 100 meq/l NaCl was administered. PMID- 8205140 TI - Anticonvulsive effects of inhaling lavender oil vapour. PMID- 8205141 TI - De novo biosynthesis of juvenile hormone III and I by the accessory glands of the male mosquito. AB - The role of the male accessory glands (MAG) in reproduction was investigated in the mosquito Aedes aegypti. MAG incubated with [14C]acetate synthesized radioactively labeled JH III, JH III bisepoxide and methyl farnesoate. MAG incubated with L-[methyl-3H]methionine synthesized [3H]JH III and a molecule that chromatographed on HPLC with JH I. Analysis of MAG and whole males extract by glass capillary combined gas-chromatography-selected ion monitoring mass spectrometry identified JH III and I as the main analogs that were synthesized by male mosquitoes. MAG of Culex nigripalpus, Anopheles rangeli and Anopheles trinkae also synthesized JH III from L-[methyl-3H]methionine, which indicates that the male mosquito has a complete JH III biosynthetic pathway. Unfed and unmated Culex quinquefasciatus do not develop their ovaries to the resting stage. Females injected with one MAG extract equivalent or implanted with A. aegypti MAG developed their ovaries to the resting previtellogenic stage, whereas females that were injected with saline did not. These results indicate that MAG synthesize and secrete JH III. The corpora allata (CA) of the male Aedes aegypti also synthesize JH III from L-[methyl-3H]methionine. This observation may suggest that JH synthesized by the male's CA is used for internal regulation, whereas JH synthesized by the MAG is transferred with the sperm into the female. PMID- 8205142 TI - Sequence of three cDNAs encoding an alkaline midgut trypsin from Manduca sexta. AB - We have purified trypsin from the midgut of Manduca sexta and shown it has an alkaline pH optimum of 10.5. In order to clone the midgut trypsin, a DNA probe was generated using the polymerase chain reaction (PCR) with template isolated from a midgut cDNA library phage stock, a mixture of degenerate primers synthesized to code for the highly conserved region around the active site serine found in trypsins, and the T7 sequencing primer. Three different trypsin cDNAs were isolated each of which encodes a preproenzyme of 256 amino acids with a putative signal sequence of 17 amino acids, an activation peptide of seven amino acids and a mature trypsin of 232 amino acids. The encoded midgut trypsins contain the highly conserved residues, Asp, His, Ser, involved in catalysis in serine proteases, along with the residues which define the trypsin specificity pocket. Sequence comparisons show that all sequences are similar to other invertebrate and vertebrate serine proteases, but they differ in that two of the three encoded trypsins have an odd number of cysteines. Northern analysis localizes the trypsin mRNA to the middle third of the midgut. A large number of arginines (19, 20 and 21) are encoded by the three cDNAs which may stabilize the trypsin, by remaining protonated, in the alkaline midgut of M. sexta. PMID- 8205143 TI - Intracellular transduction of trehalose synthesis by hypertrehalosemic hormone in the fat body of the tropical cockroach, Blaberus discoidalis. AB - Fat body of adult male Blaberus discoidalis cockroaches exposed to B. discoidalis hypertrehalosemic hormone (HTH) in vitro showed a decline in tissue glycogen as carbohydrate increased in the medium. In vivo HTH injections increased hemolymph carbohydrate and fat body glycogen phosphorylase activity > 2-fold compared to controls. In vivo trehalose synthesis was unaffected by agents that enhance intracellular levels of cyclic nucleotides including: dibutyrl cAMP, dibutyryl cGMP, forskolin (adenylyl cyclase activator) and isobutyl methylxanthine (IBMX) or theophylline (cAMP phosphodiesterase inhibitors). DbcAMP+IBMX stimulated trehalose biosynthesis of fat body in vitro and had additive effects with a minimally stimulatory HTH concentration. However, adenylyl cyclase activity was unaffected by HTH either with isolated fat body or fat body membrane preparations. We conclude that cAMP is not a second messenger for HTH, but cAMP can stimulate trehalose production independent of HTH through actions on common regulatory events related to trehalose biosynthesis. Dibutyryl cGMP and phorbol esters and diacylglycerol (activators of protein kinase C) also failed to stimulate trehalose biosynthesis in vitro. Extracellular Ca2+ enhanced HTH dependent phosphorylase activity, glycogenolysis and hypertrehalosemia and maintained basal levels of phosphorylase a at twice those observed in the absence of Ca2+. However, Ca2+ entry by Ca2+ ionophore (A23187) did not mimic HTH effects. Results of these studies demonstrated that extracellular Ca2+ is important for HTH-dependent trehalose biosynthesis but cAMP and cGMP are not involved. PMID- 8205144 TI - Prostaglandin biosynthesis by fat body from the tobacco hornworm, Manduca sexta. AB - We describe prostaglandin (PG) biosynthesis by microsomal-enriched preparations of fat body from larvae of the tobacco hornworm Manduca sexta. Four major PGs were synthesized under most experimental conditions, PGA2, PGE2, PGD2 and PGF2 alpha. PGA2, was the predominant product under most conditions. Unlike mammals, in which PGA2, is generally thought to arise from non-enzymatic rearrangements of PGE2, the fat body preparations did not convert exogenous PGE2 into PGA2. These findings suggest that PGA2 is an important fat body product that is synthesized by a route that does not involve PGE2. The PG synthase activity and the overall profile of PG synthesis were sensitive to experimental conditions, including incubation time, temperature, and protein concentration. Optimal PG biosynthesis was observed with 1 mg of microsomal-rich protein, incubated at 30 degrees C for 1-2 min. The fat body preparations is sensitive to two non-steroidal anti inflammatory drugs, indomethacin and naproxen, both of which inhibited PG synthesis at low dosages. PMID- 8205145 TI - The basic benefits package. How important is it to providers? PMID- 8205146 TI - Heart of the community. Interview by Jim Montague. PMID- 8205147 TI - The fading stand-alone hospital. AB - A new joint survey by Hospitals & Health Networks and Deloitte & Touche is confirming the shift toward integrated delivery: a majority of survey respondents say they either belong to or are developing an integrated delivery system. But are many integration initiatives all talk and little action? Data analysis reveals that many hospital executives believe they're far more integrated than they really are. Exactly how far has the reality progressed? PMID- 8205148 TI - For-profits. The right medicine for some markets? AB - The aggressive systems-building strategies the nation's large for-profit systems are pursuing are shaking up markets across the country. But while some have accused the for-profits of focusing on empire-building, the reality of their strategic implementations is surprisingly complex. PMID- 8205149 TI - Finding our roots through the arts. PMID- 8205150 TI - Data detente. Community health information networks: leaders seek cooperation amid competition. PMID- 8205151 TI - HCFA: changing with the times. Interview by Renee Blankenau. PMID- 8205152 TI - CME: a school for survival? PMID- 8205153 TI - Are there lessons to be learned from other industries? Strategy by analogy. PMID- 8205154 TI - Investing in the future. PMID- 8205155 TI - Washington, DC. The capital's a company town--but the company's not quite there yet. PMID- 8205156 TI - Data watch. AHA data: hospital expenses slowed in 1993. PMID- 8205157 TI - Interest rate swap keeps system's integration plans on track. PMID- 8205158 TI - Pharmacists join the clinical team, enhancing outcomes, reducing costs. PMID- 8205159 TI - 10 attributes of the financially capable hospital. PMID- 8205160 TI - Melatonin receptors in peripheral tissues: a new area of melatonin research. AB - Melatonin is synthesized and secreted by pineal gland, retina, harderian gland, lacrimal gland, and gut. It is a lipid-soluble molecule with ubiquitous distribution and multifarious functions. Thus, along with the better established sites of melatonin action, such as brain, retina, and pituitary, direct melatonin actions on other peripheral tissues should also be considered. The presence of melatonin receptors in peripheral tissues was rightfully hypothesized. Earlier studies on melatonin receptors had limited success. The advent of 2 [125I]iodomelatonin, a labelled melatonin agonist with a specific activity as high as 2,200 Ci/mmol, has allowed the studies of melatonin receptors with picomolar affinity and femtomolar density. Putative melatonin receptors demonstrated by autoradiography and/or radioreceptor assay in gut, kidney, lung, heart, vas deferens, and blood vessels are discussed. PMID- 8205161 TI - Melatonin and its receptors in the gastrointestinal tract. AB - Melatonin and its synthesizing enzymes have been demonstrated in the gastrointestinal tract, suggesting the in situ biosynthesis of melatonin by the gut tissues. There appears to be a diurnal rhythm of melatonin in the gastrointestinal tissues of birds and rodents, with high levels in the dark period. Release of gut melatonin into the general circulation, however, was recorded following tryptophan treatment. Melatonin has direct gastrointestinal functions: it decreased serotonin-induced gut concentration, alleviated serotonin induced reduction in gastric glandular mucosal blood flow, diminished epithelial sodium absorption, and inhibited the proliferation of jejunal epithelium. The use of a radiolabeled melatonin agonist, 2-[125I]iodomelatonin, has allowed the study of putative melatonin receptors in the gut of duck, mouse, chicken and human. The gastrointestinal 2-[125I]iodomelatonin binding to the duck, chicken and human was rapid, stable, saturable, reversible, specific and with a high affinity. The 2 [125I]iodomelatonin binding sites in the mouse gut were of a much lower affinity. In the duck gut, there was a significant variation in the densities of 2 [125I]iodomelatonin binding sites in different regions of the gut, with the following descending order of density: ileum, jejunum > duodenum, colon > cecum > esophagus. Autoradiographical studies have showed that the highest concentration of 2-[125I]iodomelatonin binding sites was in the villi of the small intestine and also in the mucosal layers of the cecum and colon. In contrast to the diurnal rhythms of 2-[125I]iodomelatonin binding sites reported in other tissues, 2 [125I]iodomelatonin binding in the duck gut showed no daily rhythm. The subcellular distribution of binding sites was in the following descending order: nuclear > microsomal > mitochondrial >> cytosolic fraction. These findings are consistent with a paracrine and/or hormonal action of melatonin in the gastrointestinal tract. PMID- 8205163 TI - Presynaptic modulation by melatonin of the nicotine-induced calcium-dependent release of norepinephrine from rat vas deferens. AB - This study demonstrates that melatonin potentiates the nicotine-induced calcium dependent release of [3H]-norepinephrine from the rat vas deferens. Slices of the prostatic portion of the rat vas deferens were labelled in vitro with [3H] norepinephrine and superfused with physiological solution. Nicotine (1 mM, 4 min) induced a calcium-dependent release of norepinephrine during the first (N1 = 1.43 +/- 0.16%) and the second (N2 = 1.11 +/- 0.2%, n = 22) nicotine stimulations. The ratio N2/N1 between two consecutive periods of nicotine stimulations was: 0.84 +/ 0.09 (n = 22). Melatonin (10-300 nM) did not modify the spontaneous release of [3H]-norepinephrine but potentiated in a concentration-dependent manner the calcium-dependent release. The competitive melatonin receptor antagonist luzindole did not modify the calcium-dependent release of [3H]-norepinephrine when added alone but completely antagonized the potentiation of release elicited by melatonin, suggesting interaction at the level of a melatonin receptor. We conclude that melatonin potentiates the nicotine-evoked release of [3H] norepinephrine in the rat vas deferens through activation of melatonin presynaptic heteroreceptors on noradrenergic nerves involved in a positive feedback mechanism. This mechanism may mediate the increase in sympathetic neurotransmission observed with melatonin in the vas deferens. We cannot exclude, however, an effect of melatonin on cellular proteins and enzymes associated with the exocytotic process, which directly or indirectly may lead to the facilitation of release. PMID- 8205162 TI - 2-[125I]iodomelatonin binding sites in the rat vas deferens. AB - To further understand the mechanism by which melatonin potentiates noradrenergic transmission in the rat vas deferens, we localized and partially characterized 2 [125I]-iodomelatonin-binding sites in tissue sections of the rat vas deferens using quantitative autoradiography. High-affinity 2-[125I]-iodomelatonin-binding sites were localized around the lumen of the prostatic portion, but not in the epididymal portion of the rat vas deferens. The binding of 2-[125I]-iodomelatonin to sections of the prostatic portion was stable, reversible and saturable. Saturation studies revealed a single class of high-affinity binding sites with a dissociation constant (Kd) of 104.2 +/- 23.7 pM (n = 4) and a binding capacity (Bmax) of 2.07 +/- 0.19 fmol/mg of protein (n = 4). These results suggest that melatonin may regulate sympathetic neurotransmission through activation of specific melatonin receptors in the prostatic portion of the rat vas deferens. PMID- 8205164 TI - [125I]iodomelatonin binding sites in mammalian and avian kidneys. AB - [125I]Iodomelatonin binding sites have been identified and characterized in kidneys of birds and mammals. These binding sites in the kidneys of guinea pig, duck and chicken were found to be stable, reversible, saturable, specific and of high affinity. The binding densities (Bmax) of [125I]iodomelatonin binding sites in the kidneys of guinea pig, duck and chicken ranged from 1.07 to 6.43 fmol/mg protein and the equilibrium dissociation constants (Kd) from 19.2 to 44.6 pmol/l at the middle of the light period (mid-light). It appears that [125I]iodomelatonin binding in the kidneys of mammalian species may have lower densities compared with birds. In the mammals studied, the guinea pig kidney showed the highest [125I]iodomelatonin binding. Pharmacological data indicated that the [125I]iodomelatonin binding to kidneys of guinea pig, duck and chicken was highly specific to melatonin, 2-iodomelatonin and 6-chloromelatonin. Diurnal variations in the Bmax of [125I]iodomelatonin binding sites were detected in the kidneys of duck and chicken with no difference in affinity. However, there was no diurnal variation in the Kd or Bmax in the guinea pig kidneys. The density of [125I]iodomelatonin binding sites in the cortex of guinea pig kidney was more than 8-fold higher than the binding in the medulla. Guanosine 5'-O-(3 thiotriphosphate) (GTP gamma S; 10 mumol/l) reduced the Bmax and increased the Kd of [125I]iodomelatonin binding sites in the chicken kidney. However, in the membrane preparations of the guinea pig kidney, co-incubation with GTP gamma S (15 mumol/l) increased the Kd with no effect on the Bmax of the [125I]iodomelatonin binding. The effects of GTP gamma S on the kidney [125I]iodomelatonin binding suggest that these binding sites may couple to a G protein. The identification of [125I]iodomelatonin binding sites in the kidneys of mammals and birds supports the possibility of melatonin acting directly on the renal system. PMID- 8205165 TI - Vascular melatonin receptors. AB - High-affinity melatonin receptors are expressed in the tail artery of the rat and arteries forming the circle of Willis of the rat and certain primates. The characteristics of the vascular melatonin receptors seem to be similar to the ones described in the central nervous system. The expression of vascular melatonin receptors in the rat is differentially regulated by factors such as strain and age, and in the female by reproductive hormones. Functional studies using the caudal artery of the rat suggest that melatonin regulates vascular tone. The highly restricted distribution of melatonin receptors in arteries involved in regulating blood flow to areas involved in heat dissipation suggests that vascular melatonin receptors may have a specific function in thermoregulatory homeostasis. PMID- 8205166 TI - 2-[125I]iodomelatonin binding sites in the lung and heart: a link between the photoperiodic signal, melatonin, and the cardiopulmonary system. AB - The pineal gland plays an important role in seasonal adaptation including variation in energy requirement. Animals exhibiting seasonal changes in their energy expenditure would be benefited if their cardiac and pulmonary systems respond to the pineal photoperiodic signal, melatonin, appropriately. Thus, we would like to hypothesize that melatonin receptors are present in the heart and lung. Using a specific labeled melatonin agonist, 2-[125I]iodomelatonin, binding sites were demonstrated in the lung and heart of birds and other animals. In the chicken lung, there were high affinity (equilibrium dissociation constant, Kd = 9.11 +/- 0.73 pmol/l) and low density (maximum number of binding sites, Bmax = 1.29 +/- 0.16 fmol/mg protein) 2-[125I]iodomelatonin binding sites that were highly specific to melatonin. Similar binding with lower density was demonstrated in the quail and frog lungs. In the duck heart, specific 2-[125I]iodomelatonin binding sites with a Kd of 30.5 +/- 3.5 pmol/l and a Bmax of 0.46 +/- 0.1 fmol/mg protein (n = 4) were demonstrated. Competitive studies suggested that these binding sites were specific to melatonin. Thus, saturable and reversible 2 [125I]iodomelatonin binding was present in the lung and heart membrane preparations of birds and possibly other animals. The picomolar affinity, femtomolar density and highly specific pharmacological profile of these binding sites suggest that they can be classified as ML-1 melatonin receptors. The 2 [125I]iodomelatonin binding sites described in the lung and heart as well as those binding sites demonstrated in other peripheral tissues suggest the ubiquitous direct action of melatonin on peripheral tissues. PMID- 8205167 TI - Fever without apparent source on clinical examination, lower respiratory infections in children, bacterial infections, and acute gastroenteritis and diarrhea of infancy and early childhood. PMID- 8205168 TI - Respiratory syncytial virus infection in children. AB - Molecular epidemiologic studies have shown that during respiratory syncytial virus (RSV) epidemics several subgroups of viruses cocirculate. On the other hand, very similar strains can be found from widely separated countries at the same time. Nosocomial outbreaks make no exception because multiple sources of virus have also been found within one outbreak. Management of RSV infections has thus far varied largely but based on the recent reports some conclusions can be drawn. Beta-Sympathomimetics have been shown to be of benefit in the treatment of bronchiolitis whereas there is no data to support the use of systemic corticosteroids. Use of ribavirin cannot be recommended in common practice but it seems to have some beneficial effect in the high-risk patients. Mortality risk in the high-risk patients seems to have decreased in latest analyses compared with earlier reports. This has been attributed to improved supportive intensive care management and advances in cardiac surgery. Gammaglobulin has potential both in short-term prophylaxis and treatment of RSV infections. Development of a safe and effective vaccine is one of the main topics in RSV research. Despite some encouraging reports of active prophylaxis, such as use of recombinant fusion protein or temperature-sensitive mutants, we will probably not see a vaccine in clinical practice in the near future. PMID- 8205169 TI - Epidemiology, management, and prevention of meningococcal infections. AB - Neisseria meningitidis is the cause of significant morbidity and mortality worldwide, both in epidemic and endemic disease form. The use of serotyping, subtyping, and multilocus electrophoresis has had a significant impact on determination of the epidemiology of meningococcal disease. Recent advances in understanding the pathogenesis of meningococcal disease, include information on the role of cytokines and other inflammatory mediators, which may contribute to establishment of additional diagnostic and treatment options. Early treatment is required to improve outcome along with the use of prophylaxis to prevent secondary disease. Vaccines against groups A, C, Y, and W135, are available but have limitations, with regard to efficacy and duration of protection. Over the past decade there has been rapid progress in the development of a vaccine against group B disease, with protective trials underway in several countries. However, varying results have been found and these vaccines have not reached a stage of providing universal protection against group B meningococcal disease. PMID- 8205170 TI - Bacterial meningitis in children. AB - Bacterial meningitis is an important problem in childhood. Vaccines can prevent Haemophilus influenzae type b disease and are being developed for infections caused by meningococci and pneumococci. Lumbar puncture is an important part of the diagnostic workup although care is required with its use. Once meningitis is diagnosed, antibiotic treatment should be started forthwith, even before hospital admission. Third-generation cephalosporins are the treatment of choice in children over 3 months of age. Increases in antibiotic resistance, especially among pneumococci, are of concern. The next few years should see major advances in the immunoprophylaxis of these serious infections. PMID- 8205171 TI - The management of otitis media with effusion: goodbye to grommets? Commentary. PMID- 8205172 TI - A 5-year-old girl with varicella and acute onset of fever, stridor, and respiratory distress. PMID- 8205173 TI - Hematology and oncology. PMID- 8205174 TI - Screening for cancer susceptibility in children. AB - Epidemiologic studies have demonstrated that virtually every form of human cancer may aggregate in families. Genetic susceptibility plays an important role in the development of many of these cancers, yet until very recently genes associated with this susceptibility had not been identified. Over the last several years, the class of genes known as tumor suppressor genes has been most consistently implicated in hereditary cancers. Recently, genes associated with childhood tumors including retinoblastoma, Wilms' tumor, as well as with adult-onset tumors such as breast cancer and colon cancer have been either cloned or localized to specific chromosomal sites. Their isolation has encouraged the development of techniques with which to analyze cancer-prone individuals and families for the presence of germline, or constitutional, alterations of genes that may place them at high cancer risk. In the past year, the benefits and pitfalls of some of these screening assays have been studied. Also, the literature has indicated the importance of considering both ethical and psychosocial implications of our growing ability to perform predictive testing for cancer. PMID- 8205175 TI - Supportive care of immunocompromised pediatric patients. AB - The current literature in supportive care of the immunocompromised patient has shown a trend toward change in, perhaps reflecting, at least in the American literature, the national emphasis on health delivery, access, and quality of life issues. This review reflects that shift. Considerable attention is given to psychosocial issues, accessibility to care at special pediatric cancer centers, and the special problems of the adolescent. In keeping with this shift in national interest, several reports deal with the prophylaxis of infection as opposed to the treatment of established disease and the strategy of avoiding chemotherapy-related late effects in children with curable disease. PMID- 8205176 TI - The use of cytokines in children. AB - Cytokines play key roles in the control of hemopoiesis and immunity. As they become available in increasing quantities and purity through improved recombinant technology, cytokines hold great clinical promise. This article focuses on recent clinical experience with a wide variety of cytokines. For example, newer uses of recombinant human erythropoietin include treatment of anemia of prematurity, AIDS, and some hemoglobinopathies. The myeloid-stimulating factors have established a niche in the treatment of chemotherapy-induced neutropenias and as an adjunct to bone marrow transplantation. Combinations of cytokines that act at different levels of hemopoietic proliferation are being evaluated for the treatment of other causes of neutropenia and thrombocytopenia and also as biologic response modifiers. PMID- 8205177 TI - Evaluation of lymphadenopathy in children. AB - This chapter provides an approach to the evaluation of lymphadenopathy in children. Malignant etiologies, including HIV-associated malignancies are reviewed. In discussing infectious agents or causes of lymphadenopathy, particular emphasis is placed on chronic regional lymphadenopathy with a focus on new advances in cat-scratch disease and tuberculous and non-tuberculous mycobacterial lymphadenitis. After a suggested preliminary set of laboratory tests, biopsy is often necessary both for histologic and cultural investigation. Therapy must be specific and must follow an accurate diagnosis. PMID- 8205178 TI - Molecular biology, pathogenesis, and prevention of hepatitis B virus infection in children. AB - Hepatitis B virus provides a model for studying the genetic variability and diversity of viruses. New molecular techniques such as the polymerase chain reaction and sequencing of amplified product enable the accurate pinpointing of genetic alteration. The immune response or lack of response to wild-type and mutant virus ultimately determines the extent of disease. Elimination of infection and disease may be achieved by natural, immunologic, and pharmacologic means, but definitive treatment may have to await the advent of gene therapy. Meanwhile, epidemiologic studies, vaccination programs, and cost-benefit analyses are important in the prevention and control of hepatitis B. Once the clinical and epidemiologic significance of mutant hepatitis B viruses is established, new strategies and vaccines will be required before elimination of the disease is achieved. PMID- 8205179 TI - Sports injuries in children. AB - More children are participating in organized sports than ever before. Although improved coaching, equipment, officiating, and rules have been implemented to reduce injuries, a significant number of young athletes continue to be injured. Fortunately, most injuries sustained by young athletes are minor requiring only symptomatic treatment. However, because of the unique features of the immature skeleton, particularly the presence of open physes, these injuries can nonetheless result in permanent alteration of bone growth with long-term morbidity and disability. Furthermore, the prognosis and natural history of sports injuries in children may be different than that for similar injuries in adults. It is important that the practitioner dealing with young athletes be aware of the unique features of children's sports injuries so that proper treatment may be initiated and prognosis and expected outcome may be intelligently discussed with the patient and parents. This review provides current information regarding sports injuries in children by summarizing the most recent pertinent articles. PMID- 8205180 TI - Fractures in children. AB - The literature published in the past year on fractures in children has helped us to increase our understanding of the natural history of fracture healing in children and introduced new techniques for fracture treatment. There is an impetus for operative fixation of femur fractures in children. The possibility is raised of growth derangement as a result of intramedullary nailing. Supracondylar fractures of the elbow continue to be a frequent topic for discussion. The benefits of adequate reduction and internal fixation have been reinforced. The incidence of nerve palsy, especially that of the anterior interosseous nerve, has been emphasized. New radiographic parameters for determining intraoperative reduction have been described. The management of radial neck fracture has been improved with percutaneous reduction proposed as an alternative to complication fraught open reduction. New information has been brought to the forefront regarding knee injuries, in particular the implications of hemarthrosis and tibial eminence fractures. Biodegradable implants have become important as they prove to be useful in children's fracture management. Such implants have been shown to be useful in fractures that do not require rigid fixation. However, biodegradable devices may be associated with foreign body reactions. PMID- 8205181 TI - Skeletal infections in children. AB - Bacteremia is an almost daily occurrence in childhood. Fortunately, infections in children are usually easily controlled and seldom produce serious sequelae. The prompt diagnosis and treatment of osteomyelitis is especially important to prevent catastrophic complications. Recent articles have pointed out that fine needle aspiration may be diagnostic in only about 60% of children with acute hematogenous osteomyelitis and have suggested that other diagnostic modalities, such as white-cell scintigraphy, ultrasound, and computed tomography, may be more sensitive. Recent recommendations about treatment of osteomyelitis included a comparison of antibiotic agents, a discussion of follow-up evaluation modalities, and a warning that the clinical effects of osteomyelitis may not be apparent until years after the infection has been successfully treated. Two articles noted the increase in the incidence of septic arthritis in children who are HIV positive and another described a chlamydial-associated syndrome of arthritis and eye involvement. The increased incidence of HIV infections also was cited by three studies as a factor in the increased incidence of tuberculosis infections in children and in the increased risk of extrapulmonary involvement. PMID- 8205182 TI - Orthopedic aspects of cerebral palsy. AB - Cerebral palsy is and will remain a significant issue for our medical and educational establishments and for society as a whole. Treatment for individuals with cerebral palsy continues to be refined and to come under increasing scrutiny for functional impact. Gait analysis and selective dorsal rhizotomy are advancements whose applicability to the majority of patients is yet to be defined. PMID- 8205183 TI - Back pain in children. AB - This article describes a quick, straightforward examination for back pain in children. The differential diagnosis is given, along with warning signs of serious causes of back pain. Guidelines are given for handling the more common problem of nonspecific back pain and minimizing unnecessary radiographs and other tests. PMID- 8205184 TI - Computer analysis of sequence data. PMID- 8205185 TI - GCG: database searching. PMID- 8205186 TI - GCG: pattern recognition. PMID- 8205187 TI - GCG: translation of DNA sequence. PMID- 8205188 TI - GCG: analysis of protein sequences. PMID- 8205189 TI - GCG: preparing sequence data for publication. PMID- 8205190 TI - MicroGenie: introduction and restriction enzyme analysis. PMID- 8205191 TI - MicroGenie: shotgun DNA sequencing. PMID- 8205192 TI - MicroGenie: translation. PMID- 8205193 TI - MicroGenie: protein analysis. PMID- 8205194 TI - MicroGenie: homology searches. PMID- 8205195 TI - GCG: drawing linear restriction maps. PMID- 8205196 TI - PC/GENE: sequence entry and assembly. PMID- 8205197 TI - PC/GENE: restriction enzyme analysis. PMID- 8205198 TI - PC/GENE: translation and searches for protein coding regions. PMID- 8205199 TI - PC/GENE: sequence comparisons and homologies. PMID- 8205200 TI - PC/GENE: database searches. PMID- 8205201 TI - PC/GENE: searches for functional sites in nucleic acids and proteins. PMID- 8205202 TI - Using the FASTA program to search protein and DNA sequence databases. PMID- 8205203 TI - Converting between sequence formats. PMID- 8205204 TI - Obtaining software via INTERNET. PMID- 8205205 TI - GCG: drawing circular restriction maps. PMID- 8205206 TI - Submission of nucleotide sequence data to EMBL/GenBank/DDBJ. PMID- 8205207 TI - GCG: displaying restriction sites and possible translations in a DNA sequence. PMID- 8205208 TI - GCG: assembly of sequences into new sequence constructs. PMID- 8205209 TI - GCG: production of multiple sequence alignment. PMID- 8205210 TI - GCG: fragment assembly programs. PMID- 8205211 TI - Calling from the rim: suicidal behavior among American Indian and Alaska Native adolescents. PMID- 8205212 TI - PRIDE: substance abuse education/intervention program. PMID- 8205213 TI - The Blue Bay Healing Center: community development and healing as prevention. PMID- 8205214 TI - Suicide ideation and suicide attempt among American Indian and Alaska Native boarding school adolescents. PMID- 8205215 TI - American Indian adolescent suicidal behavior in detention environments: cause for continued basic and applied research. PMID- 8205216 TI - Indian adolescent suicide: the epidemiologic picture in New Mexico. PMID- 8205217 TI - When communities are in crisis: planning for response to suicides and suicide attempts among American Indian tribes. PMID- 8205218 TI - The state's role in suicide prevention programs for Alaska Native youth. PMID- 8205219 TI - A study of suicide attempts comparing adolescents to adults on a northern plains American Indian reservation. PMID- 8205220 TI - Indian adolescent suicide: clinical and developmental considerations. PMID- 8205221 TI - Depressive and suicidal symptoms in Indian school children: findings from the Flower of Two Soils. PMID- 8205222 TI - The Zuni Life Skills Development curriculum: a collaborative approach to curriculum development. PMID- 8205223 TI - Copper-ligand interactions and physiological free radical processes. Part 2. Influence of Cu2+ ions on Cu(+)-driven .OH generation and comparison with their effects on Fe(2+)-driven .OH production. AB - In our search to establish a reference .OH production system with respect to which the reactivity of copper(II) complexes could then be tested, the influence of free Cu2+ ions on the Cu+/H2O2 reaction has been investigated. This influence depends on the CCu2+/CCu+ ratio. At low Cu2+ concentrations, .OH damage to various detector molecules decreases with increasing Cu2+ concentrations until CCu2+/CCu+ reaches unity. Above this value, .OH damage increases sharply until CCu2+/CCu+ becomes equal to 5 with salicylate and 2 with deoxyribose, ratios for which the protective effect of Cu2+ cancels. Finally, at higher concentrations, Cu2+ ions logically add their own .OH production to that normally expected from Cu+ ions. The possible origin of this unprecedented alternate effect has been discussed. The possible influence of Cu+ ions on the generation of .OH radicals by water gamma radiolysis has also been tested and, as already established for Cu2+ in a previous work, shown to be nonexistent. This definitely confirms that either form of ionised copper cannot scavenge .OH radicals in the absence of a ligand. PMID- 8205224 TI - A hydrogen-donating monohydroxamate scavenges ferryl myoglobin radicals. AB - The addition of 25 microM hydrogen peroxide to 20 microM metmyoglobin produces ferryl (FeIV = O) myoglobin. Optical spectroscopy shows that the ferryl species reaches a maximum concentration (60-70% of total haem) after 10 minutes and decays slowly (hours). Low temperature EPR spectroscopy of the high spin metmyoglobin (g = 6) signal is consistent with these findings. At this low peroxide concentration there is no evidence for iron release from the haem. At least two free radicals are detectable by EPR immediately after H2O2 addition, but decay completely after ten minutes. However, a longer-lived radical is observed at lower concentrations that is still present after 90 minutes. The monohydroxamate N-methylbutyro-hydroxamic acid (NMBH) increases the rate of decay of the fenyl species. In the presence of NMBH, none of the protein-bound free radicals are detectable; instead nitroxide radicals produced by oxidation of the hydroxamate group are observed. Similar results are observed with the trihydroxamate, desferrioxamine. "Ferryl myoglobin" is still able to initiate lipid peroxidation even after the short-lived protein free radicals are no longer detectable (E.S.R. Newman, C.A. Rice-Evans and M.J. Davies (1991) Biochemical and Biophysical Research Communications 179, 1414-1419). It is suggested that the longer-lived protein radicals described here may be partly responsible for this effect. The mechanism of inhibition of initiation of lipid peroxidation by hydroxyamate drugs, such as NMBH, may therefore be due to reduction of the protein-derived radicals, rather than reduction of ferryl haem. PMID- 8205225 TI - Bimodal pattern of killing of Chinese hamster V79 variant cells by hydrogen peroxide. AB - To elucidate the mechanism of cytotoxicity of H2O2, we selected H2O2-resistant Chinese hamster V79 cells by single-step selection from a pool of spontaneous variants. The resistant cells showed bimodal sensitivity to H2O2 without exhibiting a significantly higher level of the detoxicating enzymes, catalase, glutathione peroxidase and superoxide dismutase. Mode-one and mode-two killing were observed at lower (< 300 microM) and higher (> 2 mM) H2O2 concentrations, respectively. Mode-one but not mode-two killing was prevented by iron chelators. Pretreatment with low concentrations of ascorbic acid preferentially enhanced the killing at higher H2O2 concentrations. These resistant cells were cross-resistant to t-butyl hydroperoxide and cumene hydroperoxide. PMID- 8205226 TI - Formation of hydroxyl radicals on reaction of hypochlorous acid with ferrocyanide, a model iron(II) complex. AB - Hypochlorous acid reacts with the model iron(II) complex, ferrocyanide (Fe(CN)6(4 )) in aqueous solution with the rate constant 220 +/- 15 dm3 mol-1 s-1. Free hydroxyl radicals are formed in this reaction in 27% yield as shown by the hydroxylation of benzoate to give a product distribution identical to that of free (radiolytically generated) hydroxyl radicals. This reaction is three orders of magnitude faster than the analogous reaction involving hydrogen peroxide (the Fenton reaction), suggesting that the hypochlorous acid generated by activated neutrophils may be a source of hydroxyl radicals. PMID- 8205227 TI - Inhibition of microsomal lipid peroxidation and monooxygenase activities by eugenol. AB - Previously we reported that eugenol (4-allyl-2-methoxyphenol) inhibits non enzymatic peroxidation in liver mitochondria (E. Nagababu and N. Lakshmaiah, 1992, Biochemical Pharmacology. 43, 2393-2400). In the present study, we examined the effect of eugenol on microsomal mixed function oxidase mediated peroxidation using Fe+3-ADP-NADPH, carbon tetrachloride (CCL4)-NADPH and cumene hydroperoxide (CumOOH) systems. In the presence of eugenol the formation of thiobarbituric acid reactive substances (TBARS) was decreased in all the systems (IC50 values: 14 microM for Fe+3-ADP-NADPH, 4.0 microM for CCl4-NADPH and 15 microM for CumOOH). Oxygen uptake was also inhibited to a similar extent with Fe+3-ADP-NADPH and CumOOH systems. A comparative evaluation with other antioxidants showed that in Fe+3-ADP-NADPH and CumOOH systems, the antioxidant efficacy was in the order: butylated hydroxytoluene (BHT) > eugenol > alpha-tocopherol, while in CCl4-NADPH system the order was alpha-tocopherol > BHT > eugenol. Time course of inhibition by eugenol indicated interference in initiation as well as propagation of peroxidation. Eugenol did not inhibit cytochrome P-450 reductase activity but it inhibited P-450 - linked monooxygenase activities such as aminopyrine-N demethylase, N-nitrosodimethylamine demethylase, benzo(a)pyrene hydroxylase and ethoxyresorufin-O-deethylase to different extents. However, CumOOH supported monooxygenases (aminopyrine-N-demethylase and benzo(a)pyrene hydroxylase) required much higher concentrations of eugenol for inhibition. The concentration of eugenol required to inhibit monooxygenase activities was more than that required to inhibit peroxidation in all the systems. Eugenol elicited type 1 changes in the spectrum of microsomal cytochrome P-450. These results suggest that the inhibitory effect of eugenol on lipid peroxidation is predominantly due to its free radical quenching ability. Eugenol significantly protected against the degradation of cytochrome P-450 during lipid peroxidation with all the systems tested. These findings suggest that eugenol has the potential to be used as a therapeutic antioxidant. Further evaluation may throw more light on this aspect. PMID- 8205228 TI - Malondialdehyde formation in liver mitochondrial and microsomal fractions of vitamin E- and selenium-deficient rats as a function of alpha-tocopherol level: the effect of treatment in vitro with iron. AB - Weanling rats were given diets with adequate vitamin E and selenium or deprived of one or the other or both, nutrients. After 28 days, liver mitochondrial and microsomal fractions were prepared and alpha-tocopherol (alpha-T) and selenium measured. alpha-Tocopherol fell by eight-fold in the doubly deficient rats and selenium fell three-fold. Malondialdehyde (MDA) was found to be undetectable by a sensitive HPLC method. The fractions were subjected to peroxidative stress in in vitro using 0.5 mM Fe2+/10 mM ADP, and MDA and alpha-T were measured at intervals during 30 min. The results showed that in the mitochondrial fractions there was a lag time of at least 2 min before peroxidation became significant, during which time most of the alpha-T was consumed. In the microsomal fraction the lag phase was very short prior to the establishment of a linear rate of peroxidation, although little alpha-T was used up. It was concluded that the mitochondrial fraction withstood the peroxidative challenge better than the microsomal fraction even though the initial level of alpha-T in the microsomal fraction was about double that in the mitochondrial fraction. Selenium deficiency had no effect on the length of the lag phase of the fractions which therefore appears to be a characteristic of mitochondrial or microsomal fractions. PMID- 8205229 TI - Automatic solid-phase extraction and high-performance liquid chromatographic determination of quinidine in plasma. AB - High-performance liquid chromatography (HPLC) was used for the therapeutic drug monitoring of quinidine in clinical samples. Solid-phase extraction (SPE) was studied in both off-line and on-line modes. SPE was performed in an automatic on line mode using a fully automated Prospekt system. Extraction recoveries were in the range 97.1-99.4% for 1-2 micrograms/ml quinidine concentrations. For HPLC separation an Ultrasep RP-8 reversed-phase column was applied with acetonitrile water (9:1) containing 0.3% triethylamine (pH 2.5) as the mobile phase. The Prospekt system is recommended for the routine monitoring of quinidine in plasma samples. Concentrations were in therapeutic range (1.2-3.6 micrograms/ml). PMID- 8205230 TI - Chromatographic studies of the enantiomeric composition of some therapeutic compositions applied in the treatment of liver and kidney diseases. AB - A gas-liquid chromatographic system with alpha-cyclodextrin in formamide medium (coated on Chromosorb) was used for the separation of enantiomers of alpha pinene, beta-pinene, limonene and camphene in medicines applied in the therapy of liver and kidney diseases. The drugs under investigation were produced in Poland (Terpichol and Terpinex), in Germany (Rowachol and Rowatinex) and in Slovenia (Uroterp). It was found that, depending on the manufacturer, medicines possessing similar chemical compositions differ considerably from one another regarding the content of enantiomers, mainly those of alpha-pinene. PMID- 8205231 TI - On-line sample treatment for or via column liquid chromatography. AB - It is generally recognized that sample treatment often is the bottleneck in trace level organic analysis. As far as column liquid chromatography (LC) is concerned, the design, and commercialization, of on-line and fully automated precolumn/analytical column LC systems with diode-array UV or mass spectrometric detection is a distinct step towards solving the existing problems. Small precolumns that can be packed with sorbents of divergent selectivity, and also on line (electro)dialysis modules, have been shown to perform well in many environmental and biomedical applications. In addition, it is noteworthy that LC or rather, LC-type, trace enrichment and clean-up on such precolumns are increasingly being used as an on-line treatment step for aqueous samples prior to capillary gas chromatographic analysis. PMID- 8205232 TI - Potential of receptor-ligand interactions for sample handling in liquid and gas chromatography. AB - The use of receptor proteins for biospecific sample handling in liquid and gas chromatography is described. As a model system the uterine estrogen receptor was chosen for the isolation of 17 beta-estradiol and its synthetic agonist diethylstilbestrol. Biochemical characteristics relevant for the use of receptors in sample handling such as the kinetics of receptor-ligand binding, reproducibility and capacity are examined by means of an estrogen radioreceptor assay. Different techniques for the non-covalent immobilization of the estrogen receptor were investigated. Both protamine-coated glass fibre filters and silica particles which bind the receptor via electrostatic interactions have been used for this purpose. The use of the estrogen receptor in the isolation of 17 beta estradiol and diethylstilbestrol prior to GC-MS analysis is demonstrated and discussed. PMID- 8205233 TI - Screening method for the determination of volatiles in biomedical samples by means of an off-line closed-loop trapping system and high-resolution gas chromatography-ion trap detection. AB - A method is described for the analysis of volatile organic compounds in biological matrices (faeces and urine). The technique is based on off-line preconcentration by means of a closed-loop trapping system followed by high resolution gas chromatography-ion trap detection (HRGC-ITD) for separation and identification of the compounds. The technique has been validated for pattern recognition in faecal and urine samples from healthy volunteers. It is considered a very promising tool in metabolic research. PMID- 8205234 TI - Enantioselective assay for the determination of nisoldipine in dog, rat and mouse plasma by chiral microbore high-performance liquid chromatography combined with gas chromatography-mass spectrometry. AB - A sensitive, selective and validated method for the enantioselective determination of (+)- and (-)-nisoldipine in rat, mouse and dog plasma following administration of nisoldipine racemate is described. The alkalized plasma samples containing [13C4]nisoldipine racemate as internal standard (ISTD) were extracted once with toluene. The enantiomers of nisoldipine were quantitatively separated by high-performance liquid chromatography on a 250 x 2 mm I.D. column containing tris(4-methylbenzoate)-modified cellulose on silica. The fractions containing either the (+) or (-)-enantiomer of the analyte and [13C4]ISTD were analysed by gas chromatography with mass-selective detection in the single-ion monitoring mode. The limits of determination and detection were 0.5 and 0.2 ng/ml, respectively, the total precision was better than 7% (R.S.D. at 5 and 50 ng/ml, n = 35) and the accuracy was better than 10% (0.5-100 ng/ml, n = 23). The sum of the concentrations of the enantiomers determined with this assay corresponds to the concentration of the racemate determined independently by capillary gas chromatography with electron-capture detection (accuracy better than 15%, 1-80 ng/ml). The method was used for the analysis of more than 500 plasma samples obtained from toxicokinetic studies. PMID- 8205235 TI - Stereoselective high-performance liquid chromatographic assay of (+/-)-delmopinol in plasma using solid-phase extraction, a chiral derivatizing agent and electrochemical detection. AB - An enantioselective HPLC bioanalytical method for (+/-)-delmopinol was established in order to elucidate the pharmacokinetic behaviour of this chiral drug. (+/-)-Delmopinol and (+/-)-M1652, a structurally related compound used as internal standard, were extracted from plasma by a solid-phase extraction procedure using CN cartridges. The enantiomers were derivatized with a chiral derivatizing agent (R,R)-O,O'-di-p-toluoyl tartaric acid anhydride yielding diastereomeric derivatives which were separated on a reversed-phase column with acetonitrile-0.1 M ammonium acetate buffer (65:35, v/v) pH 5.7 as mobile phase. The resolution values of the diastereomeric derivatives of (-)- and (+)-M1652 and of the derivatives of (-)- and (+)-delmopinol were 1.03 and 1.46, respectively. The limit of quantitation was approximately 3 pmol (1 ng)/enantiomer per 0.5 ml plasma using electrochemical detection (+0.75 V versus Pd/PdO reference electrode). The effectiveness of the derivatization was > 98% and the total recovery of (+/-)-delmopinol and of (+/-)-M1652 from plasma or serum was found to be approximately 50%. The assay was applied to enantioselective pharmacokinetic investigations in humans, rats and dogs but showing here only one concentration time curve of the (+)- and (-)-delmopinol in a human subject after administering (+/-)-delmopinol in form of an aqueous mouth wash solution for 60 s. PMID- 8205236 TI - Enantioselective high-performance liquid chromatographic method for the determination of methadone in serum using an AGP and a CN column as chiral and analytical column, respectively. AB - A simple and sensitive HPLC method with ultraviolet absorption detection at 200 nm is described for the determination of methadone enantiomers in human serum, using dextropropoxyphene as an internal standard and organic solvent extraction. Separation was performed on two serially coupled columns, CN and Chiral AGP, with a mobile phase consisting of acetonitrile, dimethylocytlamine and phosphate buffer. Using 1.0 ml of serum, 5 nmol/1 of each enantiomer could be determined with an acceptable precision. No interactions from several drugs were observed. The method has been successfully used in a pharmacokinetic study. More than 2500 serum samples have been separated on the same AGP column with acceptable selectivity and resolution. PMID- 8205237 TI - CHIRBASE, a molecular database for the separation of enantiomers by chromatography. AB - A selected review on the separation of the stereoisomers of menthol by gas chromatography serves to demonstrate a new approach to tackle the increasing number of publications on enantiomer separation. The graphical molecular database CHIRBASE covers information (structural, bibliographic and chromatographic data) on liquid chromatography, supercritical fluid chromatography and gas chromatography. CHIRBASE is based on standard database software, thus meeting the requirements of "state of the art" information management in the chemical and pharmaceutical industries and academia. The scrutiny required to create and maintain a factual database revealed that the information content of the contemporary literature with respect to chromatographic data requires improvement. PMID- 8205238 TI - Simplified assay for the quantification of 2,3-dinor-6-keto-prostaglandin F1 alpha by gas chromatography-mass spectrometry. AB - Endogenous prostacyclin production is best assessed by the measurement of its excreted metabolites, of which a major one is 2,3-dinor-6-ketoprostaglandin F1 alpha (2,3-dinor-6-keto-PGF1 alpha). Gas chromatographic-mass spectrometric (GC MS) assays have been developed for this compound but are cumbersome and time consuming. We now report a modified assay for the measurement of 2,3-dinor-6-keto PGF1 alpha employing GC-MS in which sample preparation time is markedly shortened by replacing a number of extraction steps with reversed-phase column extraction and by modifying derivatization procedures. Precision of the assay is +/- 5% and the accuracy is 98%. The lower limit of detection in urine is approximately 15 pg/mg creatinine. Normal urinary levels of this metabolite were found to be 141 +/- 54 pg/mg creatinine (mean +/- S.D.). Urinary excretion of 2,3-dinor-6-keto PGF1 alpha is markedly altered in situations associated with abnormalities of prostacyclin generation when quantified using this assay. Thus, this assay provides a sensitive and accurate method to assess endogenous prostacyclin production and to further explore the role of this compound in human health and disease. PMID- 8205239 TI - Quinoxalinone derivatization of biological carboxylic acids for detection by peroxyoxalate chemiluminescence with high-performance liquid chromatography. AB - A quinoxalinone fluorescent tag is evaluated as a carboxylic acid derivatizing reagent for detection by peroxyoxalate chemiluminescence. The synthetic procedure for the quinoxalinone was modified to give a yield that is significantly increased over that reported previously. The new conditions use less hazardous reagents, and produce a final product greater than 97% pure, without the need for intermediate clean-up steps. The derivatization reaction is also modified to give increased yields of greater than 85% compared to 74% obtained previously. The post-column chemiluminescence reaction conditions are optimized to give detection limits of 500 attomole/injection-10 times lower than the fluorescence previously obtained. The reagent is used for the first time on a plasma sample extract. Typical method precision is 4%. PMID- 8205240 TI - Improved assay for plasma dihydroxyphenylacetic acid and other catechols using high-performance liquid chromatography with electrochemical detection. AB - Several modifications of an HPLC-electrochemical assay method for plasma levels of norepinephrine (NE), epinephrine (EPI), dopamine (DA), dihydroxyphenylglycol (DHPG), dihydroxyphenylalanine (DOPA) and dihydroxyphenylacetic acid (DOPAC) that improve the accuracy and reliability of DHPG, DOPA, and DOPAC measurements are described. In batch alumina extractions, increasing the amount of alumina decreased analytical recoveries of DHPG, DOPA, and especially DOPAC, and increasing the strength of the eluting acid increased recoveries of these catechols, without affecting recoveries of the amines NE, EPI and DA. Refrigeration (4 degrees C) until injection stabilized DOPAC in aqueous solution and therefore improved the reproducibility of plasma DOPAC measurements. Circulation of chilled water (15 degrees C) around the column using a water jacket decreased variability in retention times of the catechols and thereby facilitated identification of peaks, while enhancing separation of DHPG from the solvent front. Use of 6-fluoro-DOPA and 6-fluoro-DOPAC as internal standards did not improve inter-assay reliability. We recommend that in assays of plasma catechols including DOPAC, small (5 mg), precisely measured amounts of alumina be used, with a relatively strong eluting solution (e.g. 0.04 M phosphoric acid-0.2 M acetic acid, 20:80, v/v), and that the samples be refrigerated until injection, with column temperature held constant at less than 20 degrees C. PMID- 8205241 TI - Determination of oxytocin in biological samples by isocratic high-performance liquid chromatography with coulometric detection using C18 solid-phase extraction and polyclonal antibody-based immunoaffinity column purification. AB - A specific high-performance liquid chromatographic (HPLC) method is described for the reliable quantitation of oxytocin using culture media supernatants. The procedure employs solid-phase extraction, antibody-based immunoaffinity purification and isocratic HPLC with dual channel coulometric detection (ED). The lower limit of detection for this cyclic nonapeptide was 40 pg (40 fmol). Due to its relative simplicity, specificity and precision, the HPLC-ED of oxytocin is an accurate and attractive alternative to many existing quantitative methods. PMID- 8205242 TI - Improved clean-up method for the enkephalins in plasma using immunoaffinity chromatography. AB - A rapid and selective method of sample clean-up using immunoaffinity chromatography (IAC) was developed to isolate enkephalins from plasma. The enkephalin antibodies were produced utilizing novel protein carriers. Two antibodies, LE4H8 and 33FC6, were selected because of their moderate binding affinity and different epitopes. Enkephalin-spiked plasma was loaded onto the immunoaffinity column and eluted with acidic pH buffer. The eluate was derivatized with naphthalene-2,3-dicarboxaldehyde in the presence of cyanide (NDA CN), and the enkephalins were separated using reversed-phase liquid chromatography (RPLC). IAC sample clean-up of enkephalin-spiked plasma was compared to the existing solid-phase extraction method. The limit of detection for IAC was 30 pmol. The recovery of the enkephalins from plasma was 90% with a variance ranging from 2 to 9%. The immunoaffinity column was used for approximately 70 samples without any deterioration in performance. PMID- 8205244 TI - Novel high-performance liquid chromatographic method using solid-phase on-line elution for determination of metolazone in plasma and whole blood. AB - A novel solid-phase on-line elution HPLC method employing fluorescence detection to measure metolazone in plasma and whole blood has been developed. The method is sensitive and selective for metolazone and linear over a dynamic range of 1-50 ng/ml with a sample requirement of 250 microliters. The limit of quantitation for the method is 1 ng/ml and combined intra- and inter-day accuracy and precision had an error and coefficient of variation of 2.9 and 5.5%, respectively. PMID- 8205243 TI - Resolution of the enantiomers of ibuprofen; comparison study of diastereomeric method and chiral stationary phase method. AB - In this study, an indirect diastereomeric method and a direct method utilizing a chiral stationary phase (CSP) were investigated for the resolution of ibuprofen enantiomers. In the indirect method, ethylchloroformate (ECF) and 2-ethoxy-1-1 ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) were utilized as first-step derivatizing reagents in acetonitrile or toluene. In the direct CSP method, ibuprofen enantiomers were derivatized to p-nitrobenzyl ureides and then resolved on an (R)-(-)-(1-naphthyl)ethylurea CSP column. The derivatization procedure took place in 10 min with an overall inversion efficiency of 90.3%. Racemization was not observed under the derivatization conditions used. The HPLC-CSP method was utilized to study the pharmacokinetics of ibuprofen enantiomers in dog plasma after a single oral administration of 200 mg of ibuprofen racemate. PMID- 8205245 TI - High-performance liquid chromatographic determination of 3'-hydroxy-5'-(4 isobutyl-1-piperazinyl)benzoxazinorifamycin (KRM-1648) and its deacetyl metabolite in plasma, whole blood, urine and tissue samples in rats. AB - A reversed-phase high-performance liquid chromatographic method was developed for the determination of 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin (KRM-1648, I), a new rifamycin derivative, and its 25-deacetyl metabolite (KRM 1671, II) in plasma, whole blood, tissues and urine from rats. I and II were coextracted with an internal standard from each sample matrix by solid-phase extraction (Bond Elut). Plasma and urine were directly loaded onto Bond Elut, while whole blood and tissues were homogenized and extracted with methanol or dichloromethane-chloroform prior to Bond Elut extraction. The extracts were chromatographed on Shim-pack CLC-ODS(M) using acetonitrile-0.02 M citrate buffer containing 0.1 M sodium perchlorate (2:1, v/v), and peaks were detected at 643 nm. The validation data showed that the assays for I and II in plasma, whole blood, tissues and urine were selective, accurate and reproducible. PMID- 8205246 TI - Simultaneous determination of ofloxacin, norfloxacin and ciprofloxacin in human hair by high-performance liquid chromatography and fluorescence detection. AB - A high-performance liquid chromatographic method for the simultaneous determination of ofloxacin, norfloxacin and ciprofloxacin in human hair is described. A reversed-phase C18 column and a fluorescence detector with switching fluorescence wavelengths were used together with solid-phase extraction of the drugs from hair dissolved in 1 M sodium hydroxide. Reproducibility and linearity studies yielded coefficients of variation of 0.2-2.2, 1.4-3.1 and 1.5-3.4%, and correlation coefficients of 1.000, 0.999 and 0.999 within the concentration range 0.3-100 ng/ml for ofloxacin, norfloxacin and ciprofloxacin, respectively. For validation, hair samples were obtained from six subjects who had been taking one or two of the three fluoroquinolones. Assuming a hair growth-rate of 1 cm per month fluoroquinolones could be detected in the hair section(s) that had grown approximately between the dates of drug administration and hair sampling. PMID- 8205247 TI - Determination of 2,2-dimethyl-N-(2,4,6-trimethoxyphenyl) dodecanamide, CI-976, in rat plasma by reversed-phase high-performance liquid chromatography. AB - A quantitative reversed-phase high-performance liquid chromatographic procedure was developed to facilitate the preclinical development of a new Acyl CoA:cholesterol acyltransferase inhibitor, CI-976 (I). This procedure has a lower quantitation limit of 0.06 micrograms/ml and a quantitation range of 0.06 to 8.0 micrograms/ml of I in rat plasma. The method was applied to pharmacokinetic and toxicokinetic studies of I in rat. With minor modifications, it has also been employed for analysis of I in human, monkey, and rabbit plasma. PMID- 8205248 TI - High-performance liquid chromatographic analysis of methylation changes of CCGG sequence in brain and liver DNA of mice during pre- and postnatal development. AB - The change of the methylation of CpG in the CCGG sequence of brain and liver DNAs of mice during late fetal and suckling periods was determined by high-performance liquid chromatography using a reversed-phase column and 0.1 M phosphate buffer (pH 6.0) as the mobile phase. The tissue DNA was digested with the restriction enzyme, MspI, and was labeled at the 5'-end with [gamma-32P]ATP. The cpm% of deoxycytidine 5'-monophosphate (5mdCMP) in total CpG dinucleotides was calculated from the equation 5mdCMP/total CCGG (cpm%) = (5mdCMP)MspI,cpm/[(5mdCMP)MspI,cpm + (dCMP)MspI,cpm] x 100. The brain DNA exhibited a significant decrease in CpG methylation at prenatal day 18 but little change after birth. This marked decline of 5mdCMP in the CCGG sequence may be associated with the increase of enzymes before birth. The liver DNA showed considerable change during the late prenatal period. The observed changes of CpG methylation in liver DNA are indicative of the corresponding alterations of enzymes, multinucleate cells and hepatocytes. The results obtained indicate that both brain and liver cells have the development-associated changes in the conformation and transition of DNA around the time of birth. PMID- 8205249 TI - Determination of thiamine and its phosphate esters in human erythrocytes by high performance liquid chromatography with isocratic elution. AB - A high-performance liquid chromatographic method for the simultaneous determination of thiamine and its phosphate esters in human erythrocytes, using postcolumn derivatization, is presented. The sample preparation and the choice of the analytical column avoid the use of an elution gradient. The four thiamine compounds (thiamine and thiamine monophosphate, diphosphate and triphosphate) are eluted within less than 15 min with a detection limit of ca. 20 fmol. The reproducibility and accuracy of the assay are satisfactory. Normal physiological red blood cell concentrations of the four thiamine compounds are included. PMID- 8205250 TI - Determination of cefpodoxime levels in chinchilla middle ear fluid and plasma by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method has been developed to determine cefpodoxime levels in chinchilla plasma and middle ear fluid (MEF) to be used in studying otitis media. Cefpodoxime and the internal standard, cefuroxime, were separated on an ODS column (250 x 2.1 mm I.D., 5 microns Hypersil), using a mobile phase of 25 mM acetate buffer (pH 4.3)/15 mM triethylamine-acetonitrile (92.5:7.5, v/v). Following elution of cefpodoxime and the internal standard, at 3.5 and 5.9 min respectively, the acetonitrile concentration was increased to 1:1 (v/v) in a step function to elute endogenous compounds retained on the column. Sample preparation involved protein precipitation with acetonitrile. This fast, efficient protein precipitation procedure together with UV detection allows a quantitation limit of 50 ng/ml with a 50-microliters sample size. Recoveries (mean +/- S.D., n = 3) at 0.1 microgram/ml in MEF were 90.3 +/- 2.9% and 88.6 +/- 1.2% for cefpodoxime and cefuroxime respectively. Recoveries (mean +/- S.D., n = 3) at 0.1 microgram/ml in plasma were 72.1 +/- 7.3% and 81.1 +/- 1.1% for cefpodoxime and cefuroxime respectively. The method was evaluated with biological samples taken from chinchillas with middle ear infections after administering cefpodoxime proxetil. PMID- 8205251 TI - Prevention of iodine deficiency disorders by oral iodized oil. PMID- 8205252 TI - Prevention of iodine deficiency disorders by oral administration of lipiodol during pregnancy. AB - The prevalence of iodine deficiency disorders and the thyroid status of the population were studied in an endemic goitre area in Algeria. After oral administration of lipiodol (0.5 ml), three treated groups of mother-newborn couples were compared to an untreated group: group A, mothers treated 1-3 months before conception; group B, mothers treated during the first month of pregnancy; group C, mothers treated during the third month of pregnancy. Untreated mothers were used as a control (group D). After lipiodol treatment, all newborn babies and mothers were clinically euthyroid. All tested newborn babies were full term and no goitre was observed in the four groups. In the mothers, goitre prevalence and thyrotrophin levels decreased significantly, whereas maternal milk and urinary iodine and serum-free thyroxine levels were significantly higher after treatment. The rate of prematurity, stillbirths and abortions in the treated groups was reduced when compared to the untreated group, whereas placental and birth weights were significantly higher. In group D two cases of neonatal hypothyroidism were detected. Their re-evaluation confirmed that hypothyroidism was transient. Groups A, B and C were statistically different from group D with regard to neonatal thyrotrophin and thyroxine. Positive correlations were found between neonatal thyroxine and birth weights and placental weights on the one hand, and maternal urinary iodine and free thyroxine on the other. Consequently, these data indicate that oral administration of lipiodol before or during the first trimester of pregnancy normalizes thyroid function in newborn babies and mothers, increases placental and birth weight and reduces the frequency of iodine deficiency disorders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205253 TI - False negative results observed in anti-thyroid peroxidase autoantibody determination by competitive radioimmunoassays using monoclonal antibodies. AB - OBJECTIVE: Anti-thyroid peroxidase autoantibody (anti-TPO) and anti-thyroid microsomal antibody (anti-M) are strictly related, but discrepancies are sometimes observed. The aim of this study was to assess the incidence and to identify the causes of these discrepancies. DESIGN AND ANTIBODY MEASUREMENTS: Anti-M by passive hemagglutination and anti-TPO by two competitive monoclonal antibody-assisted radioimmunoassays (RIA-1 and RIA-2) were measured in 10,103 sera from 4232 subjects (663 male, 3569 female) screened for thyroid disease. RESULTS: Anti-TPO and anti-M correlated quite well (r = 0.7 and p < 0.0001 by RIA 1: r = 0.74 and p < 0.0001 by RIA-2), with discrepancies mostly limited to sera with low antibody titers. After exclusion of the latter samples, anti-TPO were detected in only 79 (1.4%) out of 5317 anti-M negative sera, but were undetectable in a more consistent proportion (130/2880 = 4.5%) of sera from patients with autoimmune thyroid disease and positive anti-M. In 61 sera of the latter group, anti-TPO was measured by a non-competitive RIA (RIA-3). Forty-one (67.7%) were positive by RIA-3, suggesting the presence of anti-TPO not competing with the monoclonal antibodies of RIA-1 and RIA-2. The remaining 20 sera had undetectable anti-TPO also by RIA-3. Nineteen (95%) of these sera had positive anti-thyroglobulin (anti-Tg) autoantibody and preincubation with thyroglobulin inhibited the agglutination reaction of anti-M tests. CONCLUSION: Anti-TPO by competitive monoclonal antibody-assisted RIA is negative in a minority of sera of patients with autoimmune thyroid disease and positive anti-M. This could be accounted for by anti-Tg producing false positives in the anti-M assay and by a subset of anti-TPO not competing with the monoclonal antibodies in the RIA. When autoimmune thyroid disease is suspected on clinical grounds, a negative anti-TPO test with a competitive RIA should be confirmed always by a non-competitive assay. PMID- 8205254 TI - Thyrotropin-releasing hormone (TRH) binding sites and thyrotropin response to TRH are regulated by thyroid hormones in human thyrotropic adenomas. AB - In order to see whether, in thyrotropic adenomas with thyrotoxicosis, plasma thyroid hormones regulate the thyrotropin-releasing hormone (TRH) binding sites and the thyrotropin (TSH) response to TRH, we investigated: the presence of TRH binding sites in two cases of thyrotropic adenomas associated with hyperthyroidism and in one case of thyrotropic adenoma secondary to thyroid failure: and the in vitro effect, in a perifusion system, of triiodothyronine (T3) on the response of TSH to TRH in three cases of TSH-secreting adenomas associated with hyperthyroidism. The TRH binding sites were absent in the adenomas associated with high levels of circulating thyroid hormones, whereas they were present in the adenoma secondary to primary thyroid failure (Kd = 47 nmol/l, Bmax = 40 nmol/kg membrane proteins). In vitro, the three adenomas spontaneously released TSH in the perifusion medium (1.49 +/- 0.06 (mean +/- SEM), 7.25 +/- 0.12 and 16.73 +/- 0.36 mIU.l-1 x 10(6) cells-1 x 2 min-1) and exhibited an ample TSH response to 10(-7) mol/l TRH pulses. In two cases, tumoral secretion of fragments was compared with those of fragments maintained since the time of surgical removal in the presence of 10(-8) mol/lT3. The TSH responses to TRH were abolished in the presence of T3 in these two cases. We conclude that thyrotropic adenomas associated with hyperthyroidism are still controlled in vivo by T3. In particular, T3 regulates the TSH response to TRH, probably via a down regulation of the TRH binding sites. PMID- 8205255 TI - Incidence of juvenile thyrotoxicosis in Denmark, 1982-1988. A nationwide study. AB - The objective of this study was to ascertain the annual incidence density of thyrotoxicosis in children under the age of 15 years in Denmark in 1982-1988. The design was based on computerized hospital registration of patient admittances in all departments of paediatrics and internal medicine of Denmark (Faroe Islands and Greenland excluded). Fifty-six children (48 girls and 8 boys) had a confirmed diagnosis of thyrotoxicosis, giving a national incidence density of 0.79/100,000 person-years. In children aged 0-4 years the incidence was very low (0.1/100,000), with no sex difference. In boys aged 5-9 years a similar low incidence was found, while in boys aged 10-14 years the incidence increased to 0.48/100,000. In girls aged 5-9 years the incidence increased to 0.96/100,000, reaching a maximum of 3.01 in the 10-14-year-old girls. In children of > 4 years of age a female preponderance of 6.7:1 was significant. It is concluded that thyrotoxicosis is a rare disorder in Danish children under the age of 15 years, and the incidence increases with age. Female preponderance is significant from early childhood. PMID- 8205256 TI - Single amino acid substitution (840Arg-->His) in the hormone-binding domain of the androgen receptor leads to incomplete androgen insensitivity syndrome associated with a thermolabile androgen receptor. AB - We have characterized the androgen receptor in a Japanese girl and her maternal cousin in a family with incomplete androgen insensitivity syndrome, and have investigated the molecular basis. Whole-cell androgen binding assay in cultured genital skin fibroblasts from both patients showed a normal maximum binding capacity and a normal apparent dissociation constant. However, androgen binding in fibroblasts from both patients decreased to 30% when the assay temperature was raised from 30 degrees C to 41 degrees C, indicating the presence of the thermolability of ligand binding to the androgen receptor. Sequence analysis of the coding exons of the androgen receptor gene from the patients revealed a single nucleotide substitution at position 2881 in exon G, resulting in the conversion of arginine (CGT) to histidine (CAT) at amino acid position 840 in the hormone-binding domain of the androgen receptor. The family study showed that the mothers and the maternal grandmother of the patients are heterozygous carriers for this mutation, whereas the father does not carry it, supporting the view that androgen insensitivity syndrome is an X chromosome-linked disorder. The single amino acid substitution may explain the qualitative abnormality of the androgen receptor displaying thermolability, which is thought to be the pathogenesis of incomplete androgen insensitivity syndrome in the patients. PMID- 8205257 TI - Detection of autoantibodies to the 65-kD isoform of glutamate decarboxylase by radioimmunoassay. AB - Autoantibodies (AAb) to glutamate decarboxylase (GAD) occur with a high prevalence in sera of newly diagnosed type I (insulin-dependent) diabetic patients. The aim of this study was to establish a GAD-AAb radioimmunoassay using 125I-labelled GAD65 and to evaluate this assay in a cross-sectional study with newly diagnosed type I diabetic patients (diabetes duration < 6 weeks). Furthermore, subjects at high risk of developing type I diabetes and individuals suffering from other autoimmune diseases were examined in this assay. For GAD-AAb detection, 125I-labelled GAD65 was incubated with 10 microliters of human serum overnight on ice. Thirty of 51 (59%) type I diabetic patients but none of the 54 healthy blood donors tested were found to be positive. A displacement step using 100,000 g supernatant from rat brain containing or not containing GAD showed the specificity of the binding of 125I-GAD65. Concerning the individuals at high risk of developing diabetes. 9/12 (75%) islet cell antibody (ICA)-positive non diabetic and 4/34 (12%) ICA-negative subjects with metabolic abnormalities were GAD-AAb positive. These results show the association between type I (insulin dependent) diabetes mellitus and the occurrence of GAD65-AAb, which possibly predicts a risk of developing the disease. PMID- 8205258 TI - Effect of octreotide on glucose tolerance in acromegaly. AB - To determine the effect of the somatostatin analog octreotide on glucose tolerance in acromegaly, we examined glucose profiles, oral glucose tolerance and the insulinogenic index in patients treated with this analog. Ninety patients participated in a long-term, prospective, open-label study. There was no significant change between mean daily blood glucose profiles at baseline or during octreotide treatment. Using glucose tolerance test criteria, 61% of 90 patients had normal baseline glucose tolerance. While on octreotide, 20% and 29% of these patients, respectively, developed impaired glucose tolerance or became frankly diabetic. Conversely, three of the patients who were diabetic at baseline (N = 11) became normal (18%) or developed impaired glucose tolerance (9%) during octreotide therapy. There was no relationship between the dose of octreotide and change in glycemic state. The insulinogenic index (insulin/glucose) response to a glucose challenge decreased uniformly in octreotide-treated patients. Female patients and those with elevated baseline insulin levels were more likely to develop diabetes mellitus during octreotide therapy. In conclusion, octreotide significantly alters glucose tolerance in patients with acromegaly, mandating glucose monitoring during this form of therapy. PMID- 8205259 TI - Serum carboxy-terminal propeptide of human type I procollagen in patients with primary hyperparathyroidism: studies in basal conditions and after parathyroid surgery. AB - This study was carried out in order to evaluate serum carboxy-terminal propeptide of human type I procollagen (PICP) in patients with primary hyperparathyroidism and to examine its changes following parathyroidectomy. Seventeen patients (four males and 13 famels, aged 53.8 +/- 3.1 SEM years) were studied in basal conditions; six patients also were investigated after successful parathyroid surgery. Mean serum PICP values of patients with primary hyperparathyroidism (194.5 +/- 27 SEM micrograms/l) were significantly higher (p < 0.001) with respect to those found in normal subjects. However, deviations from the norm (Z score values) were significantly less with respect to deviations of serum osteocalcin, alkaline phosphatase and urinary hydroxyproline/creatinine ratio. Following parathyroidectomy, it was possible to observe a discrepancy between markers of bone resorption and those of bone formation. The former tend to decrease, while the latter either do not show any significant change (serum alkaline phosphatase and serum osteocalcin) or increase (serum procollagen). The results of our investigation indicate that in basal conditions the assay of serum procollagen may be of clinical value but it would be better to use it in combination with other biomarkers of skeletal remodelling. The results obtained after parathyroidectomy are the opposite of those obtained following parathyroid hormone infusion and should be ascribed to the effect of acute hormone deficiency on collagen synthesis. The positive biochemical uncoupling following surgery might lend support to the rise of bone mineral density consistently reported in the first few months following parathyroidectomy. PMID- 8205260 TI - Cortical bone osteocalcin content and matrix composition in autosomal dominant osteopetrosis type I. AB - Several bone matrix protein constituents, including the major component collagen type I and the hydroxyapatite binding protein, osteocalcin, have been implicated in the regulation of bone turnover. Cortical bone osteocalcin, collagen and mineral content were studied in autosomal dominant osteopetrosis type I (ADO), a disorder characterized by diffuse symmetrical osteosclerosis. Iliac crest bone biopsies were obtained from eight patients (mean age 43.0 years, range 17-63 years) and compared with 16 age- and sex-matched normal controls (mean age 44.1 years, range 20-61 years). The osteocalcin level in cortical bone was increased (p < 0.03) in ADO (51.4 +/- 3.9 mg/kg bone) compared with controls (38.0 +/- 3.6 mg/kg bone). Total collagen, protein and calcium expressed per kilogram bone dry weight were without significant difference between patients and controls. The pathogenesis of ADO is most likely not related to cortical bone osteocalcin content, a protein implicated in osteoclast ontogeny and activation. These observations are in contrast to recent observations of reduced bone osteocalcin levels in osteopetrotic mutations in the rat and underscore the interspecies heterogeneity of this disorder. PMID- 8205261 TI - The degree of inhibition of thyroid follicular cell proliferation by iodide is a highly individual characteristic of each cell and differs profoundly in vitro and in vivo. AB - Pharmacological concentrations of iodide (> 1 x 10(-6) mol/l) are known to inhibit thyroid follicular cell growth in vitro. However, the inhibitory effect varies widely, depending on experimental conditions, and usually does not exceed 50%. We demonstrate that iodide (10(-4) mol/l) inhibits the growth of FRTL-5 cells in different passages by 11-67%. When five subclones of FRTL-5 cells were compared to the wild type, iodide-induced growth inhibition varied between 25% and 46%. The individual degree of inhibition of each clone was reproducible in two subsequent passages, suggesting that it is a stable constitutive trait. When FRTL-5 cells were grown first in three-dimensional clusters and then transplanted onto nude mice with high endogenous thyrotropin secretion, iodide at a serum concentration of less than 5.7 x 10(-7) mol/l nearly completely blocked cell replication in the transplants but not in the mice's own thyroid. Five cell lines, prepared from autonomously growing hyperthyroid feline multinodular goiters, were nearly completely resistant to the growth-inhibitory effect of iodide. These observations suggest that the sensitivity towards the growth inhibiting effect of iodide is a highly variable, stable trait of each thyrocyte, even in cloned cell populations. Some FRTL-5 cells and, even more so, cells prepared from autonomously growing nodular feline goiters are resistant constitutively to the growth-inhibiting effect of iodide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205262 TI - Exogenous free iodotyrosine inhibits iodide transport through the sequential intracellular events. AB - We describe a new function of exogenous iodotyrosine as a regulator of iodide transport. Porcine thyroid follicles in culture were preincubated with 0-20 mumol/l monoiodotyrosine or diiodotyrosine (DIT) in the presence of bovine thyrotropin (TSH) for 24 h; these iodotyrosines inhibited iodide uptake in a dose response manner. Extracellular [125I]DIT was actively transported to the thyroid follicle in the presence of TSH or (Bu)2cAMP. Inhibition of iodide uptake by iodotyrosine required preincubation with iodotyrosine in the presence of TSH; without TSH, iodotyrosine was ineffective. Follicles preincubated with DIT for 24 h inhibited TSH-mediated cAMP production, which is an important signal for iodide transport. Inhibition of iodide uptake and cAMP generation by iodotyrosine was negated characteristically by 3-nitro-L-tyrosine, an inhibitor of iodotyrosine deiodinase, or by methimazole, an inhibitor of thyroid peroxidase. Our findings suggest that iodotyrosine regulates iodide transport through the following sequential intracellular events: TSH-dependent iodotyrosine transport into the thyroid cell; deiodination of iodotyrosine and release in iodide; iodine organification by the peroxidase system; inhibition of cAMP generation by organified iodine; and inhibition of iodide transport. Thus, exogenous iodotyrosine can serve as an inhibitor of thyroid hormone formation only when TSH is present. PMID- 8205263 TI - Short-term starvation increases calcidiol-24-hydroxylase activity and mRNA level in rat kidney. AB - The renal mitochondrial calcidiol-24-hydroxylase activity and the corresponding cytochrome P-450 mRNA level were measured in rats subjected to short-term starvation alone or in combination with calcitriol treatment. Short-term starvation of 24 and 48 h increased the mRNA level by five- and six-fold, respectively. The 24-hydroxylase activity increased by five- and threefold, respectively. Treatment with calcitriol markedly increased the enzyme activity about 20-fold and the mRNA level about six-fold. In rats subjected to calcitriol treatment combined with 24 h of starvation, a significant further increase in enzyme activity was observed. The mRNA levels increased but the difference was not significant statistically. The results indicate that the mechanism by which starvation stimulates the enzymes is different, at least in part, from that behind the stimulatory effect of calcitriol. PMID- 8205264 TI - Pancreatic and islet blood flow in F1-hybrids of the non-insulin-dependent diabetic GK-Wistar rat. AB - Previous studies have indicated that various conditions under which an increased functional load is posed on the pancreatic islets, e.g. partial pancreatectomy and continuous glucose infusions, may influence the microcirculation of the pancreas. To investigate further the effects of elevated functional demand on the islets, the blood perfusion of the whole pancreas and the pancreatic islets was measured with a microsphere technique in an animal model presenting impaired glucose tolerance and mild hyperglycemia, namely F1-hybrids of the spontaneously non-insulin-dependent diabetic GK-Wistar rat. Normal Wistar rats served as controls. All hybrids had a pathological intraperitoneal glucose tolerance test 1 week before the blood flow measurements, which were performed in 10-12-week-old rats. Both the whole pancreatic and the islet blood flows were increased in the hybrids compared to controls. The fractional islet blood flow, i.e. the fraction of whole pancreatic blood flow diverted through the islets, also was increased in the hybrid rats (12.6 +/- 0.6% vs 9.8 +/- 0.5% in controls, p < 0.01). A bilateral abdominal vagotomy performed 30 min before the blood flow measurement markedly decreased the blood flow values of the islets and the whole pancreas in both groups of rats. After vagotomy, the islet blood flow in the hybrid rats was similar to that of the vagotomized control animals (8.2 +/- 0.8 and 7.5 +/- 1.4%, respectively). It is concluded that the increased pancreatic and islet blood perfusion observed in F1-hybrids of the GK-Wistar rat depends on a mechanism mediated by the vagus nerve. PMID- 8205265 TI - Role of the serotonergic system in the control of gonadotropin secretion in prepubertal male rats. AB - To analyze the role of brain serotonin in the control of gonadotropin secretion in prepubertal males, serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations were studied at different ages after administration of 5-hydroxytryptophan (5-HTP), a precursor of serotonin synthesis, alone or in combination with fluoxetine, a specific inhibitor of serotonin uptake; 8-hydroxy 2-(di-n-propylamino) tetralin (8-OH-DPAT), a serotonin 1A agonist; or D,L-p chlorophenylalanine methyl ester hydrochloride (PCPA), an inhibitor of serotonin synthesis. Also, serum gonadotropin concentrations were measured in castrated males implanted with silastic capsules containing testosterone or 5 alpha androstane-3 alpha, 17 beta-diol (alpha-diol). We found that: (i) the blockade of the serotoninergic system after PCPA administration did not modify basal gonadotropin secretion but did strongly reduce the response to orchidectomy; (ii) a stimulatory effect of 5-HTP on FSH secretion was only observed in intact males at the age of 8 days; (iii) the serotonin 1A agonist 8-OH-DPAT did not change serum gonadotropin concentrations; (iv) 5-HTP increased serum FSH and LH concentrations in 16-day-old castrated males; (v) FSH and LH serum concentrations decreased after 5-HTP in castrated animals implanted with testosterone, whereas castrated animals implanted with alpha-diol showed, like the intact males, a lack of response to 5-HTP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205266 TI - Purification of high-molecular-weight follicle-stimulating hormone binding inhibitor in porcine follicular fluids. AB - We performed the purification of high-molecular-weight follicle-stimulating hormone binding inhibitor (FSHBI) from porcine follicular fluids. The FSHBI activities of high-molecular-weight fractions acquired by ultrafiltration of follicular fluids from small, medium and large follicles with Centriflo CF25 membrane cone were 277.2 +/- 24.6, 176.7 +/- 3.0 and 141.3 +/- 3.6 U, respectively. By affinity chromatography of CF25 retentate with a column of Blue Sepharose CL6B, 94.1 +/- 5.3% of FSHBI activity was recovered in the unretained fraction. The FSHBI in the unretained fraction was purified by anion-exchange chromatography with a column of Mono Q and gel filtration on Sephacryl S300HR. As a result of sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of the final purified fraction, a single silver-stained band was observed at 310 kD under the non-reducing conditions. On the other hand, under the reducing conditions, SDS-PAGE revealed three bands at 178, 101 and 55 kD. A double reciprocal plot analysis of this substance showed competitive inhibition in FSH binding. The results of the present study suggest the existence of a 310 kD FSHBI composed of three subunits of 178, 101 and 55 kD in porcine follicular fluids. PMID- 8205267 TI - Suicide inactivation of aromatase in human placenta and uterine leiomyoma by 5 alpha-dihydronorethindrone, a metabolite of norethindrone, and its effect on steroid-producing enzymes. AB - Norethindrone (NET; 17 alpha-ethynyl-19-nortestosterone), a progestogen component of the contraceptive pill, irreversibly inhibits aromatase activity in human placental microsomes. However, it is known also to be aromatized in vitro and in vivo to produce a biologically very active estrogen called ethynylestradiol (EE2). It is therefore inappropriate to administer a high dose of NET to estrogen dependent cancer patients for a prolonged time period. In this study, we focused on 5 alpha-dihydronorethindrone (5 alpha-DHNET), a metabolite of NET that is not aromatizable, and the inhibitory effects of 5 alpha-DHNET on human placental and uterine leiomyoma microsomal aromatase and other steroid synthetases. 5 alpha Dihydronorethindrone showed weak affinity for both estrogen and progestogen receptors. It inhibited significantly human placental aromatase activity in a dose-dependent manner (Ki = 9.0 mumol/l; Kinact = 0.024/min), as well as that of uterine leiomyoma, but did not influence cholesterol side-chain cleavage or 17 alpha-hydroxylase, 21-hydroxylase or 11 beta-hydroxylase activities. These results suggest that 5 alpha-DHNET may be useful as an aromatase inhibitor, whose use in large doses is expected to reduce the size of estrogen-dependent tumors. PMID- 8205268 TI - The alpha-tocopherol, beta-carotene lung cancer prevention study: design, methods, participant characteristics, and compliance. The ATBC Cancer Prevention Study Group. AB - The Alpha-Tocopherol, Beta-Carotene (ATBC) Lung Cancer Prevention Study was a randomized, double-blind, placebo-controlled, 2 x 2 factorial design, primary prevention trial testing the hypothesis that alpha-tocopherol (50 mg/day) and beta-carotene (20 mg/day) supplements reduce the incidence of lung cancer and possibly other cancers. Total and disease-specific mortality and incidence of various diseases and symptoms were monitored for safety. Between 1985 and 1993, 29,133 eligible male smokers aged 50 to 69 years at entry were randomized to receive daily active supplements or placebo capsules for 5 to 8 years (median 6.1 years), accumulating 169,751 follow-up years. This report describes the study design, methods, and protocol as well as the baseline characteristics and capsule compliance of the participants. The ATBC Study is the largest lung cancer chemoprevention trial conducted to date. PMID- 8205269 TI - Risk of testicular cancer associated with surrogate measures of Agent Orange exposure among Vietnam veterans on the Agent Orange Registry. AB - A case-control analysis was undertaken to examine the association between various surrogate measures of Agent Orange exposure and testicular cancer among Vietnam veterans. Study subjects were selected from the Department of Veterans Affairs Agent Orange Registry. The case patients consisted of 97 veterans with a diagnosis of testicular cancer, and 311 veterans without any clinical diagnosis served as a comparison group. The surrogate measures were branch of service, type of duty, corps area, and location of the individual's unit in relation to recorded Agent Orange spray tracts. Only Navy veterans had a statistically significant increased risk of testicular cancer (odds ratio (OR) = 2.60; 95% confidence interval (CI), 1.08 to 6.24). Risk of testicular cancer was not significantly increased for ground troops (OR = 0.46; 95% CI, 0.25 to 0.86), for combat duty (OR = 0.91; 95% CI, 0.52 to 1.58), for service in the III Corps area (OR = 1.10; 95% CI, 0.66 to 1.84), and for being close to spray tracts within 90 days/8 km (OR = 0.99; 95% CI, 0.54 to 1.84) or 3 days/2 km (OR = 1.39; 95% CI, 0.50 to 3.80). The study results are not consistent with the hypothesis that Agent Orange may be a risk factor for testicular cancer among Vietnam veterans. PMID- 8205270 TI - Insulin as a predictor of coronary heart disease: interaction with apolipoprotein E phenotype. A report from the Multiple Risk Factor Intervention Trial. AB - The objective of this study was to examine whether fasting serum insulin is a predictor of coronary heart disease in high-risk US men, and whether any such predictive role explains the enhanced cardiovascular risk seen in subjects with the apolipoprotein (Apo) E 3/2 phenotype. This was a nested case-control study of participants in the Multiple Risk Factor Intervention Trial. Ninety-four subjects who died from coronary heart disease (post-trial follow-up) and 114 case patients with myocardial infarction (during trial) were compared to control subjects (n = 414) matched (1:2) by age, center, randomization date, and intervention group. Overall, fasting serum insulin at baseline was not associated with case-control status. (Means for cases versus controls: 16.8 and 16.6 microU/mL), although serum insulin showed significant correlations with low-density-lipoprotein cholesterol, triglycerides, and uric acid. When stratified by the three Apo E phenotypes, 3/2, 3/3, 3/4, a significant association of fasting insulin with case control status was seen for Apo E 3/2 individuals (19.9 versus 14.5 microU/mL; P = 0.02) but not for those with the other two phenotypes. Though fasting insulin is not a risk factor overall in this high-risk male population, it appears to contribute to cardiovascular risk in those with the Apo E 3/2 phenotype but does not explain the increased risk seen in these subjects. This new finding, if confirmed, may throw further light on the role of insulin in atherosclerosis. PMID- 8205271 TI - Risk factors for acute myocardial infarction in a southern Chinese population. AB - Although the mortality rate from coronary artery disease in Hong Kong is only one fourth of that of northern Europe and the United States, the disease has been and remains the second major cause of death (after all cancers combined). Beginning in 1987, we have conducted a case-control study of acute myocardial infarction in four Hong Kong hospitals. This study, one of the biggest case-control studies conducted in the Chinese population of both men and women, confirms the importance of several risk factors--cigarette smoking, history of hypertension, history of diabetes, body fatness, and lack of physical activity--previously described in data collected in western populations. In addition, more adverse childhood experience was also found to be an important risk factor of acute myocardial infarction. Further research in appropriate intervention measures in education in the prevention and cessation of smoking, the control of blood pressure, diabetes, and overweight, and adequate exercise could significantly help reduce the risk of acute myocardial infarction in the Hong Kong Chinese population. PMID- 8205272 TI - The Western Sydney Stroke Risk in the Elderly Study. A 5-year prospective study. AB - Aging of the Australian population, as in other developed nations, will ensure that stroke remains one of the most important causes of death and disability. The Stroke Risk in the Elderly (SITE) study aims to measure prospectively the independent contribution of dietary, sociodemographic, blood lipid, blood pressure, and hemostatic factors to risk of stroke and other cardiovascular outcomes. The target population included all independently living men and women aged 65 years and over, residents in several retirement villages in western metropolitan Sydney, New South Wales, Australia. The study cohort consists of 225 men and 787 women, selected as a convenience sample from all eligible residents in the local government areas (LGAs) adjacent to Westmead Hospital. Participants attended a baseline session to complete dietary, life-style, medical, and sociodemographic questionnaires. Anthropomorphic variables and blood pressure were measured. Blood was taken for measurement of serum lipid, glucose, and hemostatic factors. Questionnaire results were compared with an age/sex stratified, randomly selected sample drawn from the community (in the same LGAs), in order to quantify potential sampling and selection biases. The study cohort will be followed for a minimum of 5 years. The attendance rate of eligible residents for a baseline medical, dietary, life-style, and sociodemographic assessment was 72% for males and 69% for females. The study cohort was older, better educated, less ethnically diverse, and among women, less likely to have ever been married compared to people aged over 65 years in the comparison group. The baseline results suggest that hemostatic factors may be of importance in assessing risk of cardiovascular disease, (CVD), particularly in older men.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205273 TI - Diabetes mellitus and risk of idiopathic dilated cardiomyopathy. The Washington, DC Dilated Cardiomyopathy Study. AB - An epidemiologic study was carried out to examine the possible role of diabetes mellitus and other factors in the development of idiopathic dilated cardiomyopathy. Possible associations with diabetes and other factors were examined by comparing newly diagnosed case patients (n = 129) ascertained from five Washington, DC area hospitals with neighborhood control subjects (n = 258) identified using a random-digit dialing technique. The case patients and control subjects were matched by sex and 5-year age intervals and were compared in the analysis using conditional logistic regression methods. A statistically significant association was observed between idiopathic dilated cardiomyopathy and history of diabetes (relative odds = 2.2; 95% confidence interval: 1.5 to 3.3). The association with diabetes was not explained by race, income, cigarette usage, or hypertension. A total of 28.7% (37/129) of the case patients had a reported history of diabetes, as compared with 13.6% (35/258) of the control subjects (P < 0.05). A possible interactive effect was also observed between diabetes and history of hypertension (P > 0.05). These findings support the view that diabetics, particularly those with a history of hypertension, may be at increased risk of idiopathic dilated cardiomyopathy. PMID- 8205274 TI - The alpha-tocopherol, beta-carotene lung cancer prevention trial of vitamin E and beta-carotene: the beginning of the answers. PMID- 8205275 TI - The epidemiology of lung cancer in women. AB - Female lung cancer mortality rates have increased dramatically since 1950, and in 1987 lung cancer surpassed breast cancer as the leading cause of cancer death among US women. The epidemic in women, as in men, is attributable to cigarette smoking. Smoking prevalence in women peaked in the 1960s and 1970s and has since been declining, although fully 23.5% of adult women were current smokers in 1991. As a reflection of declines in smoking prevalence, lung cancer incidence and mortality rates are declining slightly in women under 45 years old, and it is predicted that overall age-adjusted rates may begin to turn around early in the next century. Survival for the disease is poor; the relative 5-year survival rate for women diagnosed between 1981 and 1987 was only 16% for whites and 13% for African-Americans. This article describes trends in female lung cancer rates by race and age, provides staging and survival statistics, and briefly reviews the evidence on smoking and other risk factors (environmental tobacco smoke, radon, pollution, family history, previous lung disease, and diet) for lung cancer in women. PMID- 8205276 TI - Randomized trials of primary prevention of cardiovascular disease in women. An investigator's view. AB - In recent years, increasing attention has focused on the need for more research to be conducted in women on health issues directly relevant to women. No one would disagree that the need for such studies is both crucial and timely. However, while the need for more research in women is urgent, the planning and conduct of such studies must always be driven by good science. Specifically, investigations in women may have unique and important scientific and logistic problems which must be recognized and addressed. However, if the trials are well designed and conducted, they will provide a sound and reliable body of data upon which to base rational clinical decision making and public health recommendations for women from women. These general issues are discussed in the context of a particular trial, the Women's Health Study, a randomized trial of the risks and benefits of low-dose aspirin, beta-carotene and vitamin E in the primary prevention of cardiovascular disease and cancer among healthy women. PMID- 8205277 TI - Coronary heart disease and estrogen replacement therapy. Can compliance bias explain the results of observational studies? AB - The overall risk/benefit of estrogen replacement therapy (ERT) is strongly dependent on assumptions about the effect of ERT on coronary heart disease (CHD). The belief that ERT causes a substantial reduction in the risk of CHD is widespread. The studies that provide support for this belief are all nonexperimental ones. Three analyses of data from two randomized clinical trials of drug treatments for CHD have examined the association of compliance with total mortality in persons who complied with the taking of placebo. In these analyses, compliance with the taking of a placebo was associated with a reduction in overall mortality of the same magnitude as the reduction in the risk of CHD in users of ERT. The benefit of compliance with placebo was not reduced by adjustment for a large number of variables, both medical and sociodemographic, that might affect mortality. Users of ERT are compliers, and the possibility that compliance bias may account for some of the apparent benefit of ERT for CHD must be taken seriously. PMID- 8205278 TI - Eating fat or being fat and risk of cardiovascular disease and cancer among women. AB - This article first reviews the relationship between intake of saturated fat and cholesterol and atherosclerosis; then the relationship between fat intake, obesity, and disease; and finally, some of the determinants of obesity and weight gain. The percentage of saturated fat and cholesterol in the diet is the major determinant of atherosclerosis and coronary heart disease among populations. In addition, fat intake is directly related to obesity. The degree of obesity is a major determinant of blood glucose and insulin, high-density-lipoprotein cholesterol, and triglycerides. Weight gain, especially after adolescence, and high fat intake may contribute, to a greater extent, to metabolically active intra-abdominal fat and risk of disease. Fat in diet, weight gain, or obesity may play an important role in sex-steroid hormone metabolism. Hormonal changes may contribute to an increased risk of breast cancer. The risks associated with eating fat may be related to the time of development of obesity (i.e., weight gain) and the balance between effects on sex-steroid hormone metabolism and insulin-glucose metabolism. PMID- 8205279 TI - Pelvic inflammatory disease. A brief overview. AB - Most pelvic inflammatory disease (PID) is caused by the ascent of sexually transmitted disease pathogens from the endocervix. In fact, PID remains the most common serious complication of infection from sexually transmitted bacterial pathogens. PID also may be caused by normal vaginal micro-organisms (such as those associated with bacterial vaginosis) that have overgrown in the vagina. PID has been linked to the occurrence of long-term sequelae, most commonly and most importantly infertility and ectopic pregnancy. In many patients PID may remain undiagnosed and asymptomatic, and may not become evident until such long-term consequences become manifest. We briefly review the epidemiology of PID including case definitions, the prevalence of the problem, and causal pathways and associated risk factors. Risk factors for both PID and its sequelae are discussed in relation to the mechanism of ascent of associated etiologic agents from the lower to the upper genital tract. PMID- 8205280 TI - Intentional and unintentional injuries in women. An overview. AB - Injuries are the leading cause of death for females 1 to 34 years old, and a major source of preventable morbidity and mortality in middle-aged and elderly women. In the United States, 43,000 women die from injuries and approximately 1 million women are hospitalized for injuries annually. The leading causes of injury death in women are motor vehicle-related injuries (34%), suicide (14%), falls (14%), and homicide (12%). Injuries of particular concern include fatal and nonfatal falls in elderly women, homicides among young black women, suicides among young white women, work-related homicides among female convenience store workers, and fatal and nonfatal injuries in pregnant and nonpregnant women associated with domestic violence. Strategies to prevent most types of injuries are either known or being investigated. Increased efforts to develop, implement, and evaluate such interventions would help to reduce the toll of injuries on women's health. PMID- 8205281 TI - Violence and women's health. The role of epidemiology. AB - Survival, a basic indicator of health, indicates that violence is a threat to the health of women. Furthermore, the quality of women's lives is compromised by the threat of violence, which creates a sense of chronic endangerment. "Stranger danger" is a misplaced emphasis; community-based investigations in the past decade have underscored that women are at highest risk of homicide, physical assault, and sexual assault at the hands of a man they know, often their husband or male intimate. Potential contributions of the science of epidemiology are identified and the relative absence of epidemiologists working in the field is noted. Violence against women may be an important, although often ignored, confounding variable or effect modifier in studies of women's health. PMID- 8205282 TI - Occupational injury deaths among females. The US experience for the decade 1980 to 1989. AB - From 1980 through 1989, females accounted for 44% of the total employed population. Thus, occupational safety and health issues specific to the experience of women merit consideration. Research has demonstrated that the occupational fatality experience of females is not adequately described by the group of all workers. The leading cause of death for all workers is motor vehicle incidents, while the leading cause of occupational injury death of females is homicide. The National Institute for Occupational Safety and Health (NIOSH) has compiled a decade of data on the fatal occupational injury experience of US workers, providing a sufficient number of female cases to allow separate analyses. Over the decade, 3821 females died as a result of injuries sustained at work, with an average annual fatality rate of 0.82/100,000 female workers. Among industries, retail trade and services accounted for nearly half of all occupational injury deaths to females. The detailed occupations with the highest rates of work-related injury death were airplane pilots and navigators, drivers of heavy trucks, construction laborers, and police and detectives. Information on the causes of work-related injury death by occupation is fundamental to the prevention of these deaths. The causes of death in the highest-risk occupations included aircraft crashes, motor vehicle collisions, pedestrians struck by motor vehicles, and homicides by firearms. These data provide a foundation for the prevention of occupational injury deaths among females in the United States. PMID- 8205283 TI - Gender differences in completed and attempted suicides. AB - Attempted suicides occur primarily among women, while completed suicides occur primarily among men. Risk factors for both attempted and completed suicides include mental and addictive disorders, disrupted family environments, and precipitating events. This article presents an overview of findings on gender differences from epidemiologic studies of completed and attempted suicides, with a focus on suicide attempts among women, and discusses possible reasons for gender differences in suicidal behaviors. PMID- 8205284 TI - Ethics, epidemiology, and women's health. AB - Ethical issues arise throughout the conduct of epidemiologic studies, in the processes of determining the study question, designing the protocol, and implementing the study. There also is an ethical dimension when studies are not done, for example, in studies of the effect of drugs and chemicals on male reproductive capacity. Harm as well as risk must be considered in the conduct of epidemiologic studies. The ethical principles that govern research, while independently justifiable, may come into conflict. Principles that govern research also may conflict with those that predominate in clinical practice. An example is the current controversy over unblinding anonymous, newborn human immunodeficiency virus seroprevalence studies to identify potentially infected infants. As women's health becomes more prominent on the research agenda, the resolution of these conflicts will become a complex challenge to epidemiologists, ethicists, clinicians, and the communities they serve. PMID- 8205285 TI - Science, ethics guidelines, and advocacy in epidemiology. AB - This article examines current ethics guidelines for recommendations on advocacy as an acceptable activity for epidemiologists. Three sets of guidelines, those produced by the Industrial Epidemiology Forum (IEF), the International Epidemiological Association (IEA), and the Council of International Organizations of Medical Sciences (CIOMS), appear to endorse the role of advocate, although there are differences in their recommendations. The IEF guidelines hint that advocacy is appropriate, the IEA guidelines recommend separating the roles of scientist and advocate, and the CIOMS guidelines recommend advocacy dependent on the quality of epidemiologic research and on causal interpretations of the data. Advocacy in the form of public health recommendations can be justified in terms of the principle of beneficence found in the guidelines, but is a central obligation only if the aims of the profession are enlarged to include not only the study of disease but also a commitment to disease prevention. An important issue in women's health--alcohol and breast cancer--provides an illustrative example. PMID- 8205286 TI - Priorities for research to meet women's health needs. PMID- 8205287 TI - Summing up. Epidemiology's effect on women's health--and vice versa. PMID- 8205288 TI - Women's health: science and politics. AB - The scientific community, in particular the NIH, as well as the political communities of governments and advocates, have formidable goals to achieve in integrating women's health research firmly within the context of biomedical science, securing rights for women to be included in clinical studies and fostering the development and advancement of women in biomedical sciences. No one group or organization can accomplish such a task alone, nor should they. This effort requires the cooperation and collaboration of many individuals and organizations if we are to meet our ultimate goal--health for all our citizens. PMID- 8205289 TI - Epidemiology and primary prevention of cancers of the breast, endometrium, and ovary. A brief overview. AB - Cancers of the breast, endometrium, and ovary account for 41% of incident cancers among women. Many risk factors for breast cancer have been identified, but most are associated with only modest elevations in risk. Also, of all the risk factors identified, few are likely to be affected by intervention programs. The pathogenesis of breast cancer is not well understood, but estrogen and possibly estrogen plus progesterone are likely to be etiologically involved. For endometrial cancer, a major etiologic pathway is exposure to estrogen without cyclic exposure to progesterone. Most of the established risk factors for endometrial cancer appear to affect risk at least in part through this pathway. Only a few risk factors for ovarian cancer have been identified. The two most commonly suggested etiologic mechanisms for ovarian cancer are (a) that suppression of ovulation reduces risk and (b) that suppression of pituitary gonadotropins reduces risk. Each hypothesis is consistent with some, but not all, of the data. Prospects for the primary prevention of these cancers are discouraging at present because few of the risk factors identified to date are readily subject to modification, especially for breast cancer, and the underlying etiologies of these cancers are not well understood, particularly for breast and ovarian cancers. PMID- 8205290 TI - Mammography screening guidelines for women 40 to 49 and over 65 years old. AB - Many organizations in the United States recommend mammography screening at 1- to 2-year intervals for those 40 to 49 years old. In most areas of Canada and Europe, screening mammography is not recommended for women 40 to 49 years old. These differences have arisen over interpretation of data from the Health Insurance Plan (HIP) study and the Breast Cancer Detection Demonstration Project (BCDDP). The apparent benefit in the HIP study is probably attributable to poor survival of control subjects with stage 1 cancers. In the BCDDP, although high cancer detection rates by mammography and improved survival of patients with screen-detected cancer were seen, the latter was probably largely due to lead time bias. The screening studies in Canada and Europe show no evidence of effectiveness of mammography screening in women 40 to 49 years old, at least in the first 10 years after screening is initiated. For women over 65 there are few data, but screening to age 74 is probably appropriate. PMID- 8205291 TI - Cardiovascular consequences of hypertension: therapeutic effects on organ damage and on cardiovascular events. AB - All major randomized trials that have tested the effectiveness of antihypertensive therapy have exclusively or almost exclusively been based on mortality and morbidity data (fatal and non-fatal strokes, fatal and non-fatal myocardial infarctions, sudden cardiac deaths, cardiovascular mortality, mortality by any cause). Thus, trials based on the monitoring of events have succeeded in ascertaining the achievement of the most important goals of treatment of any morbid condition--the prolongation of life and prevention of incapacitating morbid events. However, a clear distinction has to be made between cardiovascular events, as measured in any randomized trial of antihypertensive therapy, and the underlying vascular lesions, which have never been measured in large randomized therapeutic trials. Therefore, the results of therapeutic trials based on events cannot be applied towards the conclusion that antihypertensive therapy has similar effects on the underlying disease. Indeed, the mechanisms responsible for the precipitation of events are often different from the mechanisms leading to disease. Both the prevention of cardiovascular events and prevention of organ damage or disease are essential goals of antihypertensive therapy. As the mechanisms leading to vascular injury and to events are, to a significant extent, different, the achievement of the two goals has to be evaluated through trials that use, separately or conjointly, different criteria- either cardiovascular events, or one or more measures of cardiovascular injury. Trials based on cardiovascular injury are now possible due to the relatively large number of quantitatively precise and reproducible techniques for evaluating organ damage accompanying hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205292 TI - Mechanical and other factors involved in vascular injury related to hypertension. AB - In essential hypertension, the structure of the resistance vessels is altered such that the internal diameter (lumen) is reduced and the ratio of the tunica media thickness to the lumen is increased. This abnormality appears to be associated more with remodelling than with growth. Thus, normalization of resistance vessel structure must be aimed both at reversing the remodelling as well as inhibiting growth. Present evidence concerning the effect of antihypertensive therapy on vascular structure suggests that the effect of such therapy on vascular structure is due more to remodelling than to growth inhibition. However, the effect on vascular structure appears to be insufficient as antihypertensive therapy is better able to reduce blood pressure than to normalize vascular structure. It is suggested that the possible role of vascular remodelling in essential hypertension requires further work, and that this may have consequences for future strategies in the development of antihypertensive drugs. PMID- 8205293 TI - Endothelium in the control of vascular tone and growth: role of local mediators and mechanical forces. AB - Three major factors are involved in the development of atherosclerotic disease: 1) increased vasoconstrictor responses of the blood vessel wall; 2) increased platelet-vessel wall interaction and activation of coagulation factors; and 3) proliferative responses of vascular smooth muscle. Vascular smooth muscle cells proliferate in the media, migrate to the intima, and again proliferate on reaching the subendothelial space. In healthy blood vessels, these events do not occur due to the absence of growth promoters and/or the presence of growth inhibitors. Endothelial cells release growth inhibitors such as heparin sulphates and transforming growth factor beta 1 (TGF beta 1) as well as nitric oxide (NO) and prostacyclin. In rat vascular smooth muscle, NO inhibits proliferation and migration, particularly that induced by angiotensin II. Under certain conditions, the endothelium also releases growth promoters, such as basic fibroblast growth factor, platelet-derived growth factor (PDGF) and endothelin 1, which also can facilitate proliferative responses. Another important source of growth factors are adhering platelets which release PDGF and TGF beta 1 (albeit in its inactive form), and monocytes which are capable of releasing various growth factors. Furthermore, mechanical forces are important in the development of atherosclerosis, including transmural pressure and, in particular, pulsatile stretch. Indeed, heart rate is an independent risk factor for coronary artery disease and pulsatile stretch in vitro causes proliferation of human coronary as well as saphenous vein smooth muscle cells. The intracellular mediators involved in these proliferative responses are tyrosine kinase and S6 kinase. Calcium antagonists reduce only PDGF-induced proliferation whereas that due to mechanical forces is unaffected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205294 TI - Hypertension as a risk factor for progression of chronic renal disease. AB - The declining mortality due to coronary artery disease and stroke has been attributed in part to improved effectiveness and application of antihypertensive therapy, and successful identification and treatment of the population at risk. In striking contrast, end-stage renal disease (ESRD) attributed to hypertension has increased annually for the last decade and will probably worsen through the year 2000. Taken together, patients with diabetic nephropathy and those with hypertensive renal disease account for the majority of new cases annually. The reasons for the striking dissociation between the success with coronary artery disease and stroke on the one hand and the inability to lessen the incidence of ESRD remain to be clarified. Evidence reveals that all levels of untreated hypertension are associated with potentially declining renal function. Data from the Hypertension Detection and Follow-up Program and other studies suggest that antihypertensive treatment can prevent or retard development of progressive renal failure. No data are readily available on repeated measurement of glomerular filtration rate during prolonged treatment of mild hypertension in patients with normal or near-normal renal function. Although the importance of blood pressure control is implicit, a theoretical framework based on data derived from experimental animals suggests that angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists may exert specific renoprotective effects beyond those achieved by blood pressure reduction per se. The results of two recent long-term prospective studies support such a formulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205295 TI - MIDAS: rationale, design and descriptive data of trial patients. The MIDAS Research Group. AB - Certain classes of antihypertensive drugs, such as calcium antagonists, appear to have antiatherogenic properties, as shown in animal models. In these experimental models, only isradipine, a potent new dihydropyridine calcium antagonist, has shown an antiatherogenic effect in doses compatible with that recommended for antihypertensive treatment in humans. The Multicenter Isradipine/Diuretic Atherosclerosis Study (MIDAS) was designed to assess the efficacy of isradipine (2.5 or 5.0 mg twice daily) compared with hydrochlorothiazide (HCTZ) in reducing the rate of progression of atherosclerotic plaque in carotid arteries, as measured by B-mode ultrasonography. MIDAS is the first clinical trial of hypertension designed to test the hypothesis that antihypertensive drug treatment may have a favourable effect on the progression of atherosclerosis in humans. MIDAS is a double-blind, randomized, controlled clinical trial involving 883 patients. The primary endpoint is the observed change in the rate of progression of the intimal-medial wall thickness of the carotid arteries, as measured quantitatively by B-mode ultrasonography over time. Changes in the mean maximum intimal-medial thickness (IMT) at 12 points in the carotid arteries (near and far walls of the common carotid, the carotid bifurcation, and internal carotid segments on both right and left sides of the neck) were measured over a 3-year period. At baseline, the mean age of the participants was 58.5 years. The mean systolic and diastolic blood pressures were, respectively, 149.8 and 96.5 mmHg. The mean duration of hypertension was 10 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205296 TI - Indication for antihypertensive treatment: superiority of ambulatory vs casual blood pressure measurement. AB - The antihypertensive effect of isradipine was studied in 45 patients with mild-to moderate hypertension (mean age 59 years) using casual and ambulatory 24-h blood pressure measurement. Patients were included into the study according to their casual blood pressure. Isradipine was started at a dose of 1.25 mg twice daily for 4 weeks, and increased to 2.5 mg twice daily if casual blood pressure was not normalized. If necessary, 3 mg of spirapril, a new angiotensin-converting enzyme (ACE) inhibitor, (n = 1) or 5 mg of pindolol (n = 1) was added. The active treatment period lasted 24 weeks. At the end of the therapy, casual blood pressure was significantly decreased (p < 0.001) from 173/103 to 150/86 mmHg, and mean ambulatory blood pressure, from 146/87 to 140/83 mmHg (p < 0.05). When patients were divided into three groups according to initial whole-day ambulatory blood pressure values (group I: < 140/90 mmHg; group II: > or = 140/90 mmHg; group III: > or = 140/<90 mmHg), no effect of treatment was detected in group I. However, whole-day blood pressure fell significantly (p < 0.001) in group II (155/96 vs 143/88 mmHg) as did systolic blood pressure (p < 0.01) in group III (150/83 vs 142/81 mmHg), whereas diastolic blood pressure remained unchanged. Thus, ambulatory blood pressure measurement may be superior to casual measurement in the decision-making process to treat hypertension, avoiding not only the phenomenon of 'white-coat hypertension', but also ineffective treatment. This conclusion, however, should be confirmed by prospective studies. PMID- 8205297 TI - Does the combination of ACE inhibitor and calcium antagonist control hypertension and improve quality of life? The LOMIR-MCT-IL study experience. AB - The LOMIR-MCT-IL study was designed to investigate the effects of different antihypertensive drugs on the quality of life (QoL) of men with mild-to-moderate hypertension. This report focuses on the subgroup of patients treated with the combination of the angiotensin converting enzyme (ACE) inhibitor captopril and the calcium antagonist isradipine. The LOMIR-MCT-IL was a double-blind multicenter, placebo-controlled, one-year follow-up study in which 368 hypertensive men, aged 40-65 years, were randomly allocated to receive either isradipine, methyldopa or placebo at three titration levels. If diastolic blood pressure (DBP) remained > 90 mmHg, captopril was added openly. The QoL evaluation introduced a qualitative self-structured subjective measure in addition to prestructured quantitative measures. The quality of life was assessed at baseline, after 6 months and at the end of the study. Methyldopa normalized DBP in 50% of patients when given as monotherapy and an additional 34% with the addition of captopril (84% total). With placebo, 36% normalized DBP and another 39% on addition of captopril (75% total) and, with isradipine, 64% normalized DBP and an additional 26% with added captopril (90% total). Assessment of QoL showed that both the placebo and the isradipine+captopril groups showed significant improvement in semantic memory after antihypertensive treatment. The isradipine+captopril group showed a clear tendency towards lower depression scores, better quality of sleep, better subjective evaluation of QoL and a more positive evaluation of personal life events in comparison to the other groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205298 TI - Evaluation of the electrocardiogram in hypertensive patients: the LOMIR-MCT-IL study experience. AB - Electrocardiograms (ECGs) of hypertensive men enrolled into the LOMIR-MCT-IL study were evaluated at entry and after 1 year of follow-up. The sensitivity of a modified version of the Minnesota Code (MC) to detect ECG abnormalities was compared with the diagnosis of the treating physician. Changes in the ECG were related to blood pressure and heart rate. A total of 368 patients with mild-to moderate hypertension were included in a double-blind multicentre study to evaluate the quality of life with different treatments (isradipine, methyldopa or placebo). ECGs of 335 patients at entry and 232 patients who completed the study were available for evaluation by the treating physician, and a central cardiology unit using the modified MC. The most frequent abnormality recognized by the MC was an abnormal P wave (n = 77, 23%). Abnormal repolarization (10%), increased voltage of the QRS (5.4%) and abnormal intraventricular conduction (10%) were the other most frequent abnormalities. No correlation was detected between the abnormal P wave and other ECG abnormalities. Patients with an abnormal P wave showed significantly higher systolic blood pressure (SBP) (p < 0.001) and heart rate (p < 0.05). At the end of follow-up, abnormal P waves were still present in 58 (25%) of the patients. In 21 patients, the abnormal P wave did not change from entry and, in 37, the abnormality developed in spite of a normalized blood pressure. In 56 patients, the abnormal P wave was no longer present. Correlation between diagnosis by the MC and the physician was poor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205299 TI - Concomitant administration of isradipine and spirapril prevents reduction of renal function induced by acute administration of spirapril in patients with reduced renal function. AB - Angiotensin-converting enzyme (ACE) inhibitors may cause a further decrease in renal function in patients who already have renal failure. The acute effects of the ACE inhibitor spirapril on renal function were investigated in 10 patients with mild-to-moderate renal failure (serum creatinine of 1.5-2.5 mg/dl). Acute oral administration of spirapril at 6 mg resulted in decreases in inulin clearance (from 53.7 +/- 12.8 to 44.6 +/- 8.8 ml/min; p < 0.02; n = 5) and in PAH clearances (from 215 +/- 141.9 to 184 +/- 37.8 ml/min; p < 0.006; n = 5). However, when the acute administration of 6 mg of spirapril was given concomitantly with isradipine at 5 mg, there were no changes in these renal function parameters. PMID- 8205300 TI - Mechanical and other factors relating to left ventricular hypertrophy. AB - Although the development of left ventricular hypertrophy in hypertension is explained as a response to increases in pressure load and wall tension, the relationship between left ventricular mass and conventional blood pressure is usually weak. This may be due to the lack of standardization and the small number of blood pressure measurements in some studies. However, even 24-h blood pressure monitoring can explain only around 25% of the variation in left ventricular mass, and repeated blood pressure measurements over 30 years have not proved better in this respect. Therefore, other factors have been considered, including anthropometric and demographic characteristics; genetic influences; differences in salt intake, physical activity and alcohol consumption; neurohumoral factors; duration of hypertension; and previous antihypertensive treatment. Antihypertensive treatment may reduce left ventricular mass and a number of prospective, randomized, comparative studies have assessed whether some (classes of) drugs are more effective than others. A meta-analysis of such studies, comparing diuretics, beta-blockers, calcium antagonists and/or angiotensin converting enzyme (ACE) inhibitors, suggests that the reduction of left ventricular mass with each of these classes is similar to the reduction obtained with the other three classes statistically combined. Of particular interest is the observation that the four studies which specifically compared an ACE inhibitor and a calcium antagonist concluded that their effects on left ventricular mass did not significantly differ. Furthermore, that agents such as minoxidil and hydralazine do not reduce left ventricular mass. PMID- 8205301 TI - Effect of isradipine on cyclosporin A-related hypertension. AB - There is evidence that calcium antagonists may have a beneficial effect on cyclosporin A (CyA)-induced hypertension after organ transplantation. In a double blind controlled trial, 50 consecutive non-diabetic first kidney-transplant recipients were randomized to receive either isradipine, a dihydropyridine calcium antagonist, or placebo. There were no significant differences in age, weight, gender, warm and cold ischaemic periods, and original renal disease between treatment groups. Treatment was started intravenously 2 h before the transplantation procedure and was subsequently continued orally for 3 months. The immunosuppressive treatment included oral CyA from day 5 after a short course of anti-T-lymphocyte immunoglobulins. Hypertension was treated with oral labetolol in combination with guanfacine if necessary. Antihypertensive medication was prescribed significantly more often (16 vs 7 patients; p < 0.05) in the placebo group. Standing systolic blood pressure was significantly lower in the isradipine group. The standing diastolic and both systolic and diastolic sitting blood pressures were similar in both groups. After 3 months, patients' mean serum creatinine was significantly lower with isradipine than with placebo (142.0 +/- 11.9 vs 164.0 +/- 10.8 mumol/l; p < 0.05). With isradipine, a significantly higher dose of CyA was needed to achieve adequate plasma levels (8.0 +/- 0.5 vs 6.2 +/- 0.5 mg/kg/day; p < 0.01). It can be concluded that isradipine is an effective antihypertensive agent after kidney transplantation and may have an influence on CyA metabolism. Furthermore, isradipine appears to ameliorate CyA induced nephropathy. PMID- 8205302 TI - Intravenous isradipine in the management of severe hypertension of pregnancy in black patients: a pilot study. AB - The ideal antihypertensive agent for lowering very high blood pressure levels rapidly in severe hypertension of pregnancy still eludes researchers. This pilot study was conducted to determine the appropriate dosage regimen for isradipine in black patients with severe hypertensive disorders of pregnancy. Ten black patients with gestational age > or = 30 (range 30-38) weeks and diastolic blood pressure (DBP) > or = 110 (range 110-148) mmHg following 2 h of bed rest were recruited following informed consent. None of the patients had symptoms or signs of hypertensive crisis. After correction of hypovolaemia (using central venous pressure monitoring) with Ringer's lactate, high blood pressure was lowered by an isradipine infusion. Fetal heart rate was continuously recorded using a cardiotocograph. All blood pressure measurements were made using the same mercury sphygmomanometer by a single observer. The infusion rate of isradipine was adjusted at regular intervals until blood pressure control (DBP < 95 mmHg) was achieved. The optimal dosage regimen in black patients was found to be an initial dose of 0.15 microgram kg-1 min-1 with increments of 0.0025 micrograms kg-1 min-1 every 15 min until blood pressure control is achieved. Thereafter, a maintenance infusion of 0.15 microgram kg-1 min-1 can be initiated. This dosage regimen is associated with neither maternal hypotension nor fetal heart rate deceleration. PMID- 8205303 TI - Treatment of hypertension with dihydropyridine calcium antagonists and aspirin. AB - The effects of dihydropyridine calcium antagonists on blood pressure and platelets, and the effects of aspirin on the circadian antihypertensive efficacy of dihydropyridines and on the 24-h platelet-activity profile, were the focus of a double-blind study. Patients with essential hypertension were treated for 8 weeks with either isradipine focus of double-blind study. Patients with essential hypertension were treated for 8 weeks with either isradipine (2.5 mg/day) or nitrendipine (10 mg/day). Aspirin (100 mg/day) was added to both treatment groups for a further 8 weeks. Measurements were taken after 4 weeks of placebo, after 8 weeks of dihydropyridine treatment, and after 8 weeks of treatment combined with aspirin. Plasma levels of beta-thromboglobulin (beta-TG) and platelet aggregation induced by serotonin were measured six times during 24 h. Both dihydropyridines significantly lowered systolic and diastolic blood pressure. The addition of aspirin to dihydropyridine treatment had no significant effects on systolic or diastolic blood pressure. Dihydropyridine treatment lowered the increased 24-h plasma beta-TG profile and inhibited platelet aggregability. Aspirin added to nitrendipine led to a further significant decrease in beta-TG levels whereas its addition to isradipine was accompanied by a partial increase in plasma beta-TG. It is concluded that increases in platelet activity in hypertensive patients can be prevented with either isradipine alone or nitrendipine plus aspirin. Aspirin in a daily dose of 100 mg does not affect the antihypertensive efficacy of calcium antagonists. PMID- 8205304 TI - Factors influencing isradipine and amlodipine binding to human plasma lipoproteins. AB - The objectives of this study were to determine the distribution of isradipine among individual plasma lipoproteins ex vivo in healthy volunteers (n = 8) and in hypercholesterolaemic patients (n = 12), and to investigate the mechanisms involved in the interaction of isradipine and amlodipine with isolated lipoprotein fractions in vitro. The distribution study ex vivo demonstrated the different relative affinity of isradipine for the plasma lipoproteins: high density lipoprotein (HDL) > low-density lipoprotein (LDL) > very low-density lipoprotein (VLDL). Isradipine binding correlated linearly with the cholesterol levels in LDL and VLDL; however, binding to HDL did not correlate with the cholesterol level in this fraction. The total binding affinity of isradipine to isolated LDL was markedly higher compared with amlodipine; total binding affinity (nKa) of isradipine vs amlodipine was (1.60 +/- 0.08) x 10(7) l/mol vs (4.14 +/- 0.33) x 10(6) l/mol, respectively. Binding to HDL was also higher with isradipine --nKa = (1.04 +/- 0.04) x 10(5) l/mol--compared with that of amlodipine: nKa = (3.82 +/- 0.18) x 10(4) l/mol. There was no significant competitive binding effect of cyclosporin A (CyA) on isradipine binding to individual lipoprotein fractions. It is likely that, in addition to the structure of surface apoproteins, the factors determining the interaction of calcium antagonists with plasma lipoproteins also include the plasma level of each lipoprotein fraction as well as the lipophilicity of the drug. PMID- 8205305 TI - Isradipine increases platelet--low-density lipoprotein binding: evidence from ex vivo studies in humans. AB - The effects of isradipine (2.5 mg twice daily) on platelet--radioiodine-labeled [123I] low-density lipoprotein (LDL) binding were measured in 16 hypertensive patients (mean age 46.2 +/- 10.7 years) with (cholesterol > 250 mg/dl; n = 8) and without (cholesterol < 200 mg/dl; n = 8) hypercholesterolaemia during 4 weeks of isradipine treatment after 4 weeks of pretreatment placebo followed by 2 weeks of post-treatment placebo periods. Radioligand LDL-binding studies revealed that isradipine induced a significant (p < 0.001) rise in maximum binding capacity (Bmax) from a mean of 1148.6 +/- 244.3 ng protein/10(9) platelets to a mean of 1262.3 +/- 204.1 ng protein/10(9) platelets [dissociation constant (Kd): 9.7 +/- 4.9 micrograms protein/ml before treatment vs 7.8 +/- 3.7 g protein/ml after treatment]. After the post-treatment placebo phase, both Bmax and Kd returned to baseline levels. When the hypercholesterolaemic patients were compared with the normocholesterolaemics, the former revealed a more pronounced increase in platelet [125I]-LDL-binding capacity. Correspondingly, the dissociation constant showed a significantly (p < 0.05) greater decrease. In accordance with these results, both total and LDL cholesterol were reduced after 4 weeks of therapy with significant (p < 0.03) rises through to the end of the post-treatment placebo period. It is suggested that the observed increase in high-affinity platelet--LDL binding with isradipine treatment reflects a state of decreased in vivo platelet activation, an effect which may be of particular clinical value in hyperlipidaemic patients. PMID- 8205306 TI - Isradipine decreases the entry of radioiodine-labelled low-density lipoproteins into the arterial wall. AB - Experimental studies have demonstrated that isradipine significantly decreases the entry of radioiodine-labelled (125I) low-density lipoproteins (LDL) into the aorta. This study aimed to investigate whether similar effects could be detected in humans as well. Twelve patients (nine men and three women, aged from 35 to 53 years), all of whom had both hyperlipoproteinaemia (either type IIa or type IIb; mean total cholesterol: 296 +/- 25 mg/dl; mean LDL cholesterol: 208 +/- 22 mg/dl) and mild-to-moderate hypertension [mean systolic blood pressure (SBP): 149 +/- 12 mmHg; mean diastolic blood pressure (DBP): 104 +/- 4 mmHg] received isradipine (2 x 2.5 mg). Autologous radiolabelled (123I) LDL was reinjected and a gamma camera used to study the LDL kinetics before (at 20 min, 2 h and 20 h) and after (at the same time intervals) treatment with isradipine. Of interest were those arterial regions that are typically sites of atherosclerotic lesions (carotid artery, femoral artery). Results revealed three different types of LDL kinetics which were not altered by isradipine treatment. The quantitative LDL entry, however, was reduced by at least 4.7% with a maximum of 23.5% (p < 0.01). Only five vascular sites with type III kinetics were detected. These data suggest that isradipine may induce functional regression of atherosclerotic lesions. PMID- 8205307 TI - Influence of calcium antagonists on platelet function and vascular prostacyclin production. AB - It is suggested that calcium antagonists can counteract the process of atherogenesis by influencing different cellular mechanisms, for example, inhibiting cellular migration and proliferation, as well as by having beneficial effects on lipid metabolism and platelet function. In an assessment of the activity of different calcium antagonists in various platelet function tests and prostacyclin (PGI2) synthesis, amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nitrendipine and verapamil were tested in vitro for their effects on adenosine diphosphate (ADP)- or collagen-induced platelet aggregation, malondialdehyde (MDA) formation and vascular PGI2 production. Nitrendipine, isradipine and nicardipine were shown to inhibit both ADP- and collagen-induced platelet aggregation at the lowest concentration (0.5 microgram/ml). The half-maximum inhibiting concentration (IC50) of isradipine (4.78 +/- 0.36 micrograms/ml for ADP-induced platelet aggregation) was significantly (p < 0.01) lower than the IC50 of all the other drugs. Nitrendipine, with an IC50 of 44.2 +/- 5.32 micrograms/ml, and nicardipine, with an IC50 of 46.74 +/- 3.83 micrograms/ml, were respectively the second and third most effective compounds. Formation of MDA was also inhibited the most by isradipine, which exerted its inhibitory properties at one-fifth the concentration needed with the other agents: the IC50 of isradipine was 0.98 +/- 0.16 microgram/ml, which was significantly different (p < 0.05) compared with the second most effective agent, verapamil, which had an IC50 of 14.92 +/- 3.78 micrograms/ml. In-vitro PGI2 production was stimulated the most by isradipine as well, producing a significant (p < 0.01) increase to 417.8 +/- 47.6 pg/mg tissue/h (control: 296.4 +/- 17.6 pg/mg tissue/h) at a concentration of 0.5 microgram/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205308 TI - Obstructive sleep apnea and hypertension--double trouble? PMID- 8205309 TI - Lipomedullipinoma and Muirhead's syndrome. PMID- 8205310 TI - Obstructive sleep apnea and blood pressure elevation: what is the relationship? Working Group on OSA and Hypertension. AB - Sleep disordered breathing has increasingly been recognised as a frequent cause of ill-health in the community. Moderate or severe forms of the most common condition, obstructive sleep apnea (OSA), occur in up to 12% of the adult male population. A substantial body of literature has been published on the potential relationship between OSA and cardiovascular disease. In particular, OSA has been associated with cardiac failure, stroke, myocardial infarction and hypertension. Part of this association may be explained by other confounders, mainly obesity, which is common in OSA patients. The present review was prepared following a workshop aimed to critically review available scientific evidence suggesting that hypertension is a direct consequence of OSA. In addition, pathophysiologic mechanisms that may be involved in the relationship between OSA and cardiovascular disease, particularly brief intermittent elevation of blood pressure and sustained systemic hypertension, are discussed. PMID- 8205311 TI - Lipomedullipinoma: a source of hypermedullipinemia. AB - Previously we reported a case of persistent hypotension associated with hypermedullipinemia (Blood Pressure 1992; 1:138-148). The hypermedullipinemia appeared to result from the autonomous secretion of medullipin I (Med I) by renomedullary interstitial cells (RIC's) in the patient's remaining endstage kidney. The patient subsequently died. At autopsy, the remaining kidney contained a yellow mass (1 x 1 x 0.5 cm) consisting of adipocytes and RIC's, termed a lipomedullipinoma. This mass was extracted and chromatographed by procedures known to yield Med I. Med I was identified following these procedures. Renal tissue outside the yellow mass failed to yield Med I. It appears that the hypermedullipinemia of this case resulted from autonomous, hypersecretion of Med I by the lipomedullipinoma. PMID- 8205312 TI - Twenty-four-hour power spectral analysis by maximum entropy method of blood pressure in primary hyperaldosteronism. AB - In the present study we estimated the periodic profiles and variance structure of systolic blood pressure, diastolic blood pressure, heart rate and mean arterial pressure by using an autoregressive model of power spectrum, Maximum Entropy Method (MEM) in 8 patients with primary aldosteronism, during long-term therapy with nicardipine slow release. The four blood pressure variables were measured at 30-min intervals, using a noninvasive device (Spacelabs 90202) in 8 hypertensive patients of whom 6 with idiopathic aldosteronism (IHA) and 2 with dexamethasone suppressible aldosteronism (DSH), before and after 24 weeks of 80 mg nicardipine daily. Blood pressure data were processed by MEM and spectral profiles were obtained. During nicardipine therapy all patients showed a significant decrease of 24-h ambulatory blood pressure values (p < 0.01). Before therapy, spectrum analysis by MEM indicated the presence of high frequency distribution of peaks for SBP, DBP, MAP and HR. The MEM power spectrum showed an increase in amplitude of sharp peaks of systolic, diastolic, MAP and heart rate in all patients after therapy at 24 h corresponding to the circadian rhythm blood pressure. Furthermore, the trend of these variables synchronized themselves in the same period after 24 weeks of nicardipine therapy, with spectral patterns of blood pressure similar to those of normotensive subjects. This chronobiologic approach, by Maximum Entropy Method, may be used as an alternative statistical analysis to search for possible rhythmic behavior of ambulatory blood pressure data before and after pharmacological treatment in secondary hypertensive patients. PMID- 8205313 TI - The Bergen Blood Pressure Study: ambulatory blood pressure in subjects with an accurately defined family history of hypertension or normotension. AB - 24-hour ambulatory blood pressure (BP) was monitored by non-invasive methods in 42 offspring of hypertensive families (age [mean (SD1)] 40(7) years) and 38 offspring of normotensive families (age 33(6) years). The family history was defined according to parental BP data from two surveys conducted 27 years apart. Casual BP was 137(17)/84(12) mmHg in offspring of hypertensive families and 117(9)/69(6) mmHg in offspring of normotensive families (difference: p < 0.001). Average 24-h BP was 123(10)/74(6) mmHg and 113(8)/65(5) mmHg, respectively (difference: p < 0.001). The systolic and diastolic BP difference of approximately 10 mmHg was observed between the groups throughout the monitoring period. Hypertension--defined according to a recent meta-analysis as an average 24-h BP > or = 139/87 mmHg--was found in 6 offspring of hypertensive families and in no offspring of normotensive families (p < 0.05). The 24-h systolic and diastolic BP load--the percentage of readings above 140/90 mmHg (day-time) and 120/80 mmHg (night-time)--was higher in offspring of hypertensive than normotensive families (27%/17% vs. 7%4%; p < 0.001). After adjustment for intrafamilial covariation, age, and other possibly confounding variables, the differences between the groups remained. The present findings suggest that BP in subjects with a family history of hypertension is elevated on a permanent basis, and not only when it is measured in the doctor's office. PMID- 8205314 TI - A comparison of isradipine and felodipine in Australian patients with hypertension: focus on ankle oedema. The Physician's Study Group. AB - The aim of this study was to compare the tolerability and efficacy of isradipine and felodipine in the treatment of mild-moderate hypertension. After a 4 week placebo period, 143 patients entered a randomized, double-blind, multicentre study of 12 weeks duration. Patients received either isradipine (n = 72) or felodipine (n = 71) 2.5 mg twice daily. Doubling of this dose and the addition of enalapril (2.5 mg once daily) was permitted if DBP was > 90 mmHg at weeks 4 and 8, respectively. Isradipine monotherapy reduced BP from 165/104 +/- 13/6 mmHg at baseline to 149/91 +/- 14/10 mmHg at week 8 (p < 0.001), while felodipine alone reduced BP from 171/104 +/- 17/6 at baseline to 151/92 +/- 19/9 (p < 0.001). Following the addition of enalapril to 35% of patients in the isradipine group BP was further reduced to 144/88 +/- 13/8 mmHg at week 12 (p < 0.001). The addition of enalapril to 24% of the felodipine group further reduced BP to 150/92 +/- 19/9 mmHg at week 12 (p < 0.001). No differences in BP were found between the 2 groups while on monotherapy. However, the isradipine group had a significantly lower DBP than the felodipine group at the conclusion of the study (p = 0.008; 95% CI 0.7 to 6.9 mmHg). Similar incidences of headache, flushing, dizziness and tachycardia were reported in both groups. However, the incidence of ankle oedema was significantly lower in the isradipine group (p = 0.028). Overall, ankle oedema was reported more often by female patients and was not associated with an increase in weight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205315 TI - Pathologic remodeling of the myocardium in a weightlifter taking anabolic steroids. PMID- 8205316 TI - Response to the endothelium-dependent vasodilator acetylcholine in perfused kidneys of normotensive and spontaneously hypertensive rats. AB - The possible role of endothelium-derived relaxing factor (EDRF) was investigated in resistance vessels of the kidney obtained from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Kidneys were studied in parallel and perfused with Tyrode's solution at constant optimal flow rates. In the presence of indomethacin, during vasoconstriction (increase in perfusion pressure) produced by prostaglandin F2 alpha, acetylcholine caused a graded dilatation (pressure fall) that was greater in kidneys of WKY than of SHR. Methylene blue and hydroquinone, but not oxyhemoglobin, inhibited the decreases in perfusion pressure induced by acetylcholine, but not those by papaverine. The results suggest that part of the renal vasodilatation induced by acetylcholine is mediated by endothelium-derived relaxing factor, and that the response is impaired in the resistance vessels of the hypertensive rat kidney. PMID- 8205317 TI - Comparison of endothelin-1 and noradrenaline stimulated inositol phosphate formation in cultured aortic smooth muscle cells from spontaneously hypertensive and Wistar Kyoto rats. AB - Total [3H]-inositol phosphate formation was measured in cultured aortic smooth muscle cells from 6 and 14 week spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) normotensive rats. Basal inositol phosphate formation was significantly increased in cells cultured from SHR compared to WKY at both 6 and 14 weeks as was basal phosphatidylinositol formation. This difference in basal values was apparent after 9 h or more incubation with [3H]-myoinositol. Both endothelin-1 and noradrenaline stimulated inositol phosphate formation was unchanged in cultured smooth muscle cells from 6-week SHR compared to WKY. In cultured smooth muscle cells from 14-week SHR a decrease was observed in endothelin-1 stimulated inositol phosphate formation compared to controls. Noradrenaline stimulated inositol phosphate formation was increased in cultured cells from 14 week SHR. Endothelin-1 and noradrenaline stimulated inositol phosphate formation does not appear to be involved in the development (at 6 weeks) of hypertension in this model. However, in established hypertension (14 weeks) cells from SHR have altered total [3H] inositol phosphate formation in response to stimulation with noradrenaline and endothelin-1 although these changes are in opposite directions. Therefore, in cultured smooth muscle cells from 14-week rats noradrenaline and endothelin-1 appear to be regulated independently with regard to their effects on the phosphatidylinositol cycle. PMID- 8205318 TI - Regional haemodynamics in Brattleboro rats during chronic ingestion of NG-nitro-L arginine methyl ester. AB - The aim of this study was to assess regional haemodynamic changes in conscious Brattleboro rats during chronic ingestion of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Animals were instrumented with renal, mesenteric and hindquarters pulsed Doppler flow probes and an intra arterial catheter, and haemodynamic measurements were made before, during and after 14 days' exposure to L-NAME (0.01 mg ml-1 in the drinking water). Within 6 h after addition of L-NAME to the drinking water, mean arterial blood pressure was increased (maximum, 33 +/- 6 mm Hg), and remained so until L-NAME was withdrawn, whereupon blood pressure returned to normal levels within 24 h. The hypertension was accompanied by a transient reduction in mesenteric blood flow, and a more persistent reduction in hindquarters blood flow. Mesenteric and, particularly, hindquarters vascular conductance showed a sustained reduction. However, during ingestion of L-NAME, renal blood flow was not diminished and, over the final 4 days of exposure to L-NAME there was no significant renal vasoconstriction. All regional haemodynamic effects of L-NAME were lost within 24 h of its withdrawal. Hence, as with shorter periods of exposure to the less potent NO synthase inhibitor, NG-monomethyl-L-arginine, the hypertension caused by L-NAME is dependent on its continued administration, and is associated with a particularly marked hindquarters vasoconstriction. PMID- 8205319 TI - The role of nitric oxide and potassium channels in endothelium-dependent vasodilation in SHR. AB - We have investigated the effects of L-NG-nitro arginine (L-NOARG), glibenclamide, ouabain, tetraethylammonium and 4-aminopyridine on the methacholine-induced endothelium-dependent vasodilation in perfused resistance arteries from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Since the concentration-response curves of MCh were similar in both types of preparations there does not seem to exist an endothelial dysfunction in mesenteric arteries of SHR. L-NOARG only partially inhibited the maximal methacholine-induced response in preparations taken from SHR and WKY rats. Ouabain decreased the maximal effect of methacholine without altering the potency (pD2). Preparations from SHR were more susceptible to ouabain. 4-aminopyridine and tetraethylammonium decreased the pD2 for methacholine without reducing the maximal effect (Emax). The WKY rat preparations were more affected by these compounds. An important role of ATP sensitive potassium channels may be ruled out since glibenclamide was without effect on the methacholine-induced vasodilation. It is concluded that endothelium derived relaxing factor is only partially responsible for the endothelium dependent vasodilation. Indirect arguments point toward a role of endothelium derived hyperpolarizing factor, since ouabain, tetraethylammonium and 4 aminopyridine inhibited the methacholine-induced response. Although hypertension related differences for these compounds were observed high blood pressure does not seem to alter the functional response to muscarinic stimulation. PMID- 8205320 TI - Syndromes associated with trichothiodystrophy. AB - Sparse, brittle, sulphur-deficient hair is an excellent marker for several autosomal recessive neurocutaneous syndromes. The term 'trichothiodystrophy' is commonly used in publications on such syndromes and the best characterized trichothiodystrophy syndrome is associated with skin photosensitivity and intellectual impairment. Patients with these three cardinal signs usually have an underlying DNA repair defect. Here we describe clinical and laboratory findings in two patients with trichothiodystrophy and defective DNA repair alongside findings in three other cases who have different trichothiodystrophy syndromes without defective DNA repair. These patients' features are discussed in the light of a practical classification scheme which is based upon a check-list of clinical abnormalities associated with trichothiodystrophy syndromes (Van Neste, 1991). PMID- 8205321 TI - DOOR syndrome: additional case and literature review. AB - We report on a patient with sensorineural deafness, onycho- and osteodystrophy and mental retardation (DOOR syndrome) and review the literature. It appears that abnormal dermatoglyphics are a frequent feature of the DOOR syndrome, as all patients with DOOR syndrome in whom dermatoglyphic investigations were done, had multiple arches on their fingertips. PMID- 8205322 TI - Greig cephalopolysyndactyly syndrome in a large family: a comparison of the clinical signs with those described in the literature. AB - We report on a four generation family with Greig cephalopolysyndactyly syndrome. The clinical variability of the malformations of hands and feet is described. A review of the literature is given, with emphasis on the frequency of clinical signs of the Greig cephalopolysyndactyly syndrome. Polydactyly of the hands and feet are possibly an underestimated feature in Greig syndrome. We suggest that radiographs of the hands and feet should be performed in every patient, especially those with broad thumbs. The resemblance of preaxial polydactyly type 4 and crossed polydactyly with Greig syndrome is discussed. These disorders may be allelic. PMID- 8205323 TI - The acrocallosal syndrome: expansion of the phenotypic spectrum. AB - A family demonstrating the acrocallosal syndrome in a female proband whose sister had anencephaly is described. Two similar cases were found in the literature (Gelman-Kohan et al., 1991; Cataltepe and Tuncbilek, 1992). Analysis of the multiplex family data suggests that anencephaly may be an extreme manifestation of the spectrum of brain anomalies associated with the acrocallosal syndrome. PMID- 8205324 TI - A fetus with an abnormal chromosome 7 and possible hydrolethalus syndrome. AB - A fetus with multiple abnormalities phenotypically similar to hydrolethalus syndrome, but also with broad thumbs, was found to have a de novo interstitial deletion of the terminal segment of the long arm of chromosome 7 and a small rearrangement within the proximal half of the p arm of the same chromosome. Terminal deletions of chromosome 7q fall into two broad phenotypic groups, neither of which resembles this fetus, but the digital anomalies are attributed to the 7p rearrangement disrupting the Greig syndrome gene. PMID- 8205325 TI - Femoral hypoplasia unusual facies syndrome with preaxial polydactyly. AB - Preaxial polydactyly of the foot is an unusual feature in femoral hypoplasia unusual facies syndrome, having been recorded with certainty in only two previous reports. We now add a further two instances of this rare association and emphasize that this finding should not preclude the underlying syndromic diagnosis. PMID- 8205326 TI - Otospondylomegaepiphyseal dysplasia: report of three sibs and review of the literature. AB - We report three sibs with clinical and radiological features of otospondylomegaepiphyseal (OSMED) syndrome. The literature is reviewed. PMID- 8205327 TI - Frontofacionasal dysplasia: a new case and review of the phenotype. AB - A boy is presented with frontofacionasal dysplasia. The severity of his malformations exceeds that encountered in the cases described previously. The range of clinical abnormality seen in this disorder is reviewed and the delineation of the condition as a separate entity is explored. PMID- 8205328 TI - Total situs inversus associated with the oculo-auriculo-vertebral spectrum. AB - A patient is reported with the association of the oculo-auriculo-vertebral spectrum and situs inversus. Conditions with overlapping features and previously reported conditions associated with the oculo-auriculo-vertebral spectrum are reviewed. These conditions, as well as the reported association of the oculo auriculo-vertebral spectrum and situs inversus can probably be seen as a part of the mesodermal malformation spectrum, due to an early abnormality in the development of the primitive streak or embryonic mesoderm. PMID- 8205329 TI - Scalp lipomas and cerebral malformations: overlap between encephalocraniocutaneous lipomatosis and oculocerebrocutaneous syndrome. PMID- 8205330 TI - [Recurrent corneal erosion]. AB - Anterior stromal puncture has been proposed as a new treatment for recurrent corneal erosion. A soft technique with a curved needle minimize scarring and prevent corneal perforation. An insertion depth of 0.1 mm was sufficient to cause the production of new basement membrane attached to the anterior stroma. GEGGEL and coll. use a new technique with multiple applications of the Nd Yag Laser on the basement membrane. The laser punctures would be more reproducible and work as well as stromal punctures. PMID- 8205331 TI - [Epidemic keratoconjunctivitis]. AB - 73 patients were diagnosed as having epidemic keratoconjunctivitis using 2 inclusions criteria: 1) Negative conjunctival smear culture and 2) Eosinophilic inclusions and chromatic nucleus in conjunctival cells. A new therapeutical approach is proposed. PMID- 8205332 TI - [A new kind of keratoprosthesis]. PMID- 8205333 TI - [HLA typing and corneal grafts]. AB - The author proposes an evaluation of studies concerning H.L.A.-typing in corneal graft. The importance of class-II antigens in corneal graft rejection is pointed out. A retrospective and prospective multicentric study should be started. PMID- 8205334 TI - Myopia: radial keratotomy versus excimer laser. AB - Myopia can be treated by radial keratomy or by excimer laser. RK is an already old procedure, excimer laser photoablation being relatively new. It is not clear which modality will best help the patient. To make up our minds, we took a sample of 8 patients, in whom we treated the first eye by RK, the second by laser. This experiment started in January 1992. Those patients were checked on anamnesis, refraction, electronic keratoscopy and follow-up. Anamnestically, every patient preferred the speed of recovery and the brightness of the sight in the RK eye and wondered why we treated the second eye with the laser. Our current attitude is to perform RK in every patient except where a bad RK-result is to be expected (high myopes, low eyepressure, very young patient, etc.), where we advise our excimer (Preference 20 to 1). PMID- 8205335 TI - [Capsulorhexis and manual extracapsular extraction]. AB - Capsulorhexis is the best method of anterior capsulectomy. It is easier to perform a small capsulorhexis, suitable for phacoemulsification than a large capsulorhexis, suitable for a manual extracapsular extraction. We describe manoeuvres enabling the control of tearing the anterior capsule in such a way that the capsulorhexis will be adapted to the passage of the nucleus during the manual extracapsular extraction. PMID- 8205336 TI - [Phacoemulsification and flexible implants]. AB - We report a study of astigmatism and postoperative complications in 170 eyes following phacoemulsification and implantation of a flexible silicone intraocular lens (SI-18NB) in the capsular bag. No significant difference existed between the preoperative mean astigmatism and the postoperative mean astigmatism after 7 days and after 1 month. Complications were infrequent and compared with those associated with PMMA intraocular lenses. PMID- 8205337 TI - [Risks of cataract extraction following retino-vitreous surgery]. AB - Extracapsular cataract extraction (ECCE) was done in 35 eyes of 30 patients after previous retinal attachment surgery with scleral buckling. A posterior chamber intraocular lens (PC-IOL) was implanted in 35 eyes. No significant modification in the cataract surgical technique was necessary. PMID- 8205338 TI - [Laser treatment of diabetic macular edema]. AB - Diabetic macular oedema may be treated by focal or by grid photocoagulations. Indications are discussed. PMID- 8205339 TI - [Graft of pigment epithelium: past, present and future]. PMID- 8205340 TI - [Retinopathy of prematurity (ROP)]. AB - In the two last years new techniques were applied for treatment of advanced R.O.P.: argon and diode indirect laser ophthalmoscope, oxygen supplementation in combination with the former or alone. We briefly present these techniques. PMID- 8205341 TI - [Cyclosporin in ophthalmology]. AB - Cyclosporine A is a selective T-cell immunosuppressant, and doesn't inhibit the phagocytic system to the same degree as do steroids. Significant nephrotoxicity has been associated with its systemic use for solid organ transplantation or chronic idiopathic uveitis. Topical administration of CsA 2% in olive oil reduces the risk of systemic side-effects and appears to be well tolerated without local toxicity. Ocular penetration currently limits its indications for corneo-scleral immune diseases or high-risk corneal grafts. PMID- 8205342 TI - [Fibrinolysis: indications in ophthalmology]. AB - The ability to realize a microcatheter urokinase infusion in central retinal artery occlusion open new ways in therapy. It provides opportunity to realize in situ thrombolysis without well-known systemic side-effects. If started during the first hours after the occlusion, that therapy could be successful and give good visual prognosis. PMID- 8205343 TI - [Surgery of the senile macular hole]. AB - According to GASS, idiopathic macular hole would be the result of a vitreo foveolar traction. Early stage would be detected and vitreo-foveolar surgery at this stage could stop the evolution to complete macular hole. First results of this surgery are hopeful. Complete macular hole surgery involves reapplication of the lifted crown of the retina around the macular hole. These results are mitigating. PMID- 8205344 TI - [Mitomycin C in glaucoma surgery]. AB - Glaucoma filtering surgery fails because of scarring of the filtering bleb. Fibroblasts proliferation from the episclera and Tenon capsule play an important role in the scarring process. The use of antimetabolites in glaucoma filtering surgery have a beneficial effect on the lowering of intraocular pressure especially in eye at poor surgery prognosis. They inhibit the fibroblasts proliferation and subsequent scarring of filtering bleb. 5 fluorouracil improves chance of success with filtering surgery but the necessity of multiple subconjunctival injections has many disadvantages including discomfort for the patient and ocular surface problems such as corneal defect and conjunctival wound leak. Mitomycin C with its focal applications limits the toxic effects to tissue directly exposed to the drug. A single intra-operative application leads to a more hypotensive effect with less corneal complications which are two major advantages of this treatment (Kitazawa and al.): Success rate at one year without medical treatment: 88% with MMC-40% with 5 FU. Different tissue culture studies as well as clinical studies demonstrate that the antiproliferative effect of MMC is 100 times more powerful than 5 fluorouracil. Mitomycin C might probably interfere with other steps in the wound healing process. Mitomycin C seems to be a better treatment than 5 fluorouracil. Nevertheless long term randomized prospective human studies are necessary to confirm it. PMID- 8205345 TI - [Care of contact lenses]. AB - Though there is a large variety of lens care systems, the following steps are always required: clearing, disinfection and rinsing. The goal to reach is removing of deposits and microorganisms to prevent infections. PMID- 8205346 TI - [Surgery of the superior rectus muscle in children less than 2 years old]. AB - DVD appears after DHD but is present in most of the cases before the age of 2. This article presents the results of a precocious surgery associating a bilateral recession of the medial recti with a uni or bilateral recession of one or both superior recti. The cause of bad results is analysed. Only 4% of the failures are unexplained. PMID- 8205347 TI - [Mini prisms in decompensated exophoria in children]. AB - This paper gives an original method to treat "intermittent exotropia" with normal binocular vision. 25 consecutive cases of exotropia have been followed, 17 cases near horizontal prism and 3 oblique prism (in association with a congenital fourth nerve paralysis). 4 patients near glasses without prism and only one was treated surgically. The results are promising and this method completes well orthoptic reeducation. PMID- 8205348 TI - [Ischemic neuropathies: current expectations in their treatment]. AB - We performed 5 decompressions of optic nerve sheaths in eyes presenting non arteritic ischemic neuropathies. We used a medial approach. We had little surgical complications and we obtained an improvement of visual functions in 3 eyes and no change in the 2 other. PMID- 8205349 TI - The relationship between aneuploidy and p53 overexpression during genesis of colorectal adenocarcinoma. AB - This paper describes the investigation of nuclear DNA content and p53 immunoreactivity in normal mucosa (n = 25), mildly (n = 15), moderately (n = 28) and severely atypical (n = 22) colorectal adenomas and in colorectal adenocarcinomas (n = 116). Twenty-seven per cent of the mildly atypical, 43% of the moderately, 77% of the severely atypical adenomas and 91% of the colorectal carcinomas were distinctly aneuploid. In the aneuploid lesions p53 immunoreactivity was not observed in mildly atypical adenomas, whereas 17% of the moderately atypical, 24% of the severely atypical adenomas and 66% of the adenocarcinomas were p53 positive. None of the diploid lesions were p53 immunoreactive. These data are interpreted to indicate that genomic instability as reflected by crude aneuploidy occurs early during genesis of colorectal carcinoma and represents a high risk factor for p53-gene mutation. PMID- 8205350 TI - Functional and morphological effects of tumour necrosis factor alpha in an interleukin 6-producing pulmonary large cell carcinoma with sarcomatoid features. AB - We established a clonal cell line, HAT.MC8, derived from a human pulmonary large cell carcinoma with sarcomatoid features. This cell line was successfully maintained in a protein-free medium and exhibited sarcomatoid fibroblastic features in vitro. The cells constitutively produced a large amount of interleukin 6 (IL-6) in vitro. Tumour necrosis factor alpha (TNF-alpha) not only stimulated HAT.MC8 cells to produce IL-6, but also induced a morphological change from sarcomatoid fibroblastic to epithelial features. Although this change was related to actin and zonula adherens, there was no evidence that E-cadherin participated in the change. Interleukin 1 beta (IL-1 beta) had a stimulatory effect on IL-6 production by HAT.MC8 cells, but no influence on the morphology of the cells. PMID- 8205351 TI - K-ras gene mutations: an unfavorable prognostic marker in stage I lung adenocarcinoma. AB - Activation of K-ras gene by point mutations, a common finding in lung adenocarcinomas, has been suggested to decrease patient survival. We investigated 109 lung adenocarcinomas, mostly small, peripheral, stage I tumours (81/109) for presence of K-ras gene mutations at codons 12 and 13. Mutations were detected by denaturing gradient gel electrophoresis analysis of specific sequences amplified by polymerase chain reaction from DNA extracted from archival pathological material. Thirty-three of 109 (30.3%) tumours showed mutations at codon 12 (28/33, 84.8%) or 13 (5/33, 15.2%) of the gene. Mutations and type of nucleotide substitutions were differently distributed among cytological subtypes, being more prevalent among less differentiated (G2 and G3) tumours and among bronchial than bronchiolo-alveolar type adenocarcinomas. Survival analysis showed an adverse effect of K-ras mutation on survival, restricted to stage I tumours. Median survival for 81 stage I patients was 30 months for non-mutated tumours versus 20 months for mutated tumours (p = 0.016). Multivariate analysis showed that age of patient (p = 0.001) and K-ras mutation status (p = 0.04) were the only independent factors influencing survival significantly. These data strengthen the hypothesis that K-ras gene mutations may be useful in identifying a subgroup of patients with poor outcome. PMID- 8205352 TI - Immunohistochemical evaluation of alpha-catenin expression in human gastric cancer. AB - E-cadherin (E-cad) plays a major role in the maintenance of cell-cell adhesion in epithelial tissues, and impaired E-cad expression correlates with tumour invasion and metastasis. Alpha-catenin (alpha-cat), an undercoat protein of adherens junctions, binds to the cytoplasmic domain of E-cad and is essential for linking E-cad to actin-based cytoskeleton. We investigated E-cad and alpha-cat expression in 60 human gastric cancers immunohistochemically. The 60 gastric cancers were classified into 18 (30%) in which alpha-cat expression was preserved, and 42 (70%) reduced cases. The reduction of alpha-cat expression was significantly related to dedifferentiation, depth of invasion, infiltrative growth and lymph node metastasis. We also examined the co-expression of alpha-cat and E-cad. Seventeen (28%) tumours preserved both molecules [alpha-cat(+)/E-cad(+)] and 33 (55%) tumours reduced both [alpha-cat(-)/E-cad(-)], whereas 9 (15%) tumours exhibited alpha-cat(-)/E-cad(+). The frequency of lymph node metastasis in alpha cat(-)/E-cad(+) tumour (67%) was significantly higher than that in alpha-cat(+)/E cad(+) tumours (24%) and was close to that in alpha-cat(-)/E-cad(-) tumours (82%). The frequency of haematogenous liver metastasis in alpha-cat(-)/E-cad(+) tumours (44%) was significantly higher than that in alpha-cat(+)/E-cad(+) tumours (6%) or alpha-cat(-)/E-cad(-) tumours (9%). Thus, in all E-cad(+) tumours, the frequency of lymph node and liver metastasis was higher in alpha-cat(-) tumours than in alpha-cat(+) tumours. alpha-Cat expression is apparently better at predicting tumour invasion and metastasis than E-cad expression. PMID- 8205354 TI - Expression of type-2 histo-blood group carbohydrate antigens (Le(x), Le(y), and H) in normal and malignant human endometrium. AB - Changes in expression of histo-blood group ABH and Lewis antigens are common alterations in carcinomas. Using immunohistochemistry, we have evaluated the expression of type-2 histo-blood group antigens in normal and malignant endometrial tissues in relation to genetic and hormonal factors. The Le(x), sialosyl-Le(x), and Le(y) antigens were inconstantly expressed in the normal endometrium. The expression was uninfluenced by the secretor status but was related to the ABO blood group status in Oestradiol (E2) stimulated endometria. Le(y) was expressed most frequently in proliferating endometria from blood group 0 individuals. Le(x) and Le(y) were maximally expressed in atrophic endometria, and Le(x) and Le(y) staining scores correlated inversely with serum levels of E2 in normal, non-secretory endometria. No correlation was found in adenomatous hyperplasias and endometrial carcinomas, which when compared with atrophic endometria, showed a loss of Le(x) and Le(y) and an increased H-carbohydrate expression at apical membranes. Carcinomas from non-secretors showed lower expression of Le(y) and H-antigens than carcinomas from secretors. Our findings suggest that the genetic and hormonal influence on glycosylation based on type-2 chain carbohydrates differ between normal and malignant endometrium. This difference is probably related to specific tumour-associated qualitative and quantitative changes in the fucosyltransferases. PMID- 8205353 TI - Cytokine release by human bone marrow cells: analysis at the single cell level. AB - Regulation of haemopoiesis is closely mediated by a number of growth factors in the marrow microenvironment. The identification of the cell type secreting these regulatory polypeptides is difficult due to the heterogeneity of bone marrow cells. To analyse the release of haemopoietic growth factors by normal human bone marrow cells at the single cell level, we employed the reverse haemolytic plaque assay (RHPA). Freshly isolated human marrow cells were examined for the release of interleukin-1 alpha (IL-1 alpha), IL-3, IL-6 and granulocyte-monocyte colony stimulating factor (GM-CSF). In order to identify various cytokine-secreting cell types, the RHPA was combined with immunocytochemical or enzymatic staining. The total of secreting marrow cells as well as the amount of several secretory haemopoietic subpopulations could be determined with this technique under various conditions. Following incubation with pure serum-free medium without addition of any mediator, only few cells secreting either IL-1 alpha, IL-3, IL-6 or GM-CSF could be observed. After 2 h incubation with recombinant human-IL-1 alpha (rhIL-1 alpha) (10.0 ng/ml) or rhGM-CSF (10.0 pg/ml) the number of cytokine-secreting cells significantly increased for all secretory products tested. Using cytochemical staining reactions, we were able to identify 55% of all cells secreting a specific cytokine. Glycophorin C-positive erythropoietic cells turned out to be the largest fraction (up to 89%) of cytokine-releasing haemopoietic cells, followed by neutrophil granulocytes (between 6 and 48%), and monocytes/macrophages (between 4 and 23%). Only few CD 61-positive cytokine secreting megakaryocytes could be detected. Dose- and time-dependent kinetics after stimulation with rhGM-CSF revealed that the bulk of secretory activity originates from haemopoietic or rather from erythropoietic cells following low level stimulation and after short stimulation time. Thus, our data are in keeping with the assumption, that especially erythropoietic cells are producing a repertoire of cytokines that is thought to exhibit regulatory functions within marrow microenvironment. In the present study the RHPA is presented as an appropriate tool for measuring cytokine release not only of cells of the haematopoietic system but also of other tissues, for example solid tumours or malignant lymphomas. PMID- 8205355 TI - Polyploidy in cardiac myocytes of normal and hypertrophic human hearts; range of values. AB - Two-wavelength scanning DNA cytophotometry was used for DNA and protein estimation in human ventricular myocytes. In many hypertrophic hearts weighing more than 500 g the DNA content assessed by ploidy of myocytes, was within the range of normal adult variation (4-10c, where c is the haploid DNA content). A correlation was found between the protein content of myocytes and the weight of the hypertrophic ventricle. In congenital heart disease, the excessive polyploidy (up to 15-20c) developed through the normal route of myocyte polyploidization in childhood. Excessive polyploidization was revealed only in overloaded hypertrophied ventricles. A correlation was identified between the ploidy level, the ventricular weight and age of the child. Excessive polyploidy was also detected in adults with congenital or acquired in childhood diseases. There was no correlation between the myocyte ploidy and age. We propose that childhood polyploidy excess persists in these adults. The ranges of polyploidy are compared with the recent data on genome: protein ratio in cardiac myocytes and the interrelationships allow us to discuss the significance of childhood heart polyploidy as a reserve utilised under pathological conditions in adults. PMID- 8205356 TI - Analysis of herpesvirus genomes in Kikuchi's disease. AB - We examined the cervical lymph nodes of 30 patients with Kikuchi's disease and 15 patients with non-specific lymphadenitis, using Southern blot analysis and polymerase chain reaction (PCR) to identify human herpesviruses such as Epstein Barr virus (EBV), cytomegalovirus, herpes simplex virus, and varicella-zoster virus. By Southern blot analysis, no virus DNA was recognized, but 16 of the 30 nodes from patients with Kikuchi's disease and 8 of the 15 nodes from patients with non-specific lymphadenitis showed amplified EBV DNA by PCR. PMID- 8205357 TI - Coexistence of papillary and medullary carcinoma of the thyroid gland-mixed or collision tumour? Clinicopathological analysis of three cases. AB - We present three thyroid carcinomas displaying medullary and papillary components. In two cases the papillary component was characterized by typical papillae with a fibrovascular core; in one a follicular variant of papillary carcinoma was found. The papillary component was dominant in two and the medullary in one case. One tumour showed clear-cut borders between the two components, the others displayed an intermingled pattern. Both tumour components were seen in lymph node metastases with immunostaining with antibodies to calcitonin, chromogranin A, carcinoembryonic antigen, other neuroendocrine markers and thyroglobulin. At least two of our cases are true mixed carcinomas probably arising from a common stem cell. PMID- 8205358 TI - Expression of insulin-like growth factor II by a gastric carcinoma associated with hypoglycaemia. AB - A gastric cancer with liver metastases was associated with low morning levels of plasma glucose (24 mg/dl), insulin (< 2.5 microU/ml) and growth hormone (0.23 ng/ml). Primary and metastatic tumour tissue stained positively with anti-insulin like growth factor II (IGF-II) monoclonal antibody. Western immunoblot analysis revealed a high molecular weight IGF-II in the serum: 15 kDa (normal: 7.5 kDa). Postmortem reverse transcription polymerase chain reaction on mRNA from both sites revealed 471 base pairs size cDNA encoding prepro-IGF-II. These results suggest that the gastric carcinoma encoded, expressed, and secreted IGF-II, probably causing the extrapancreatic tumour hypoglycaemia. PMID- 8205359 TI - Measuring the steady-state value and the dynamics of the skin blood flow using the non-contact laser speckle method. AB - The non-contact laser speckle method provides a measure of skin blood flow with a time resolution of 1 s. Information about different characteristics of the blood flow can be obtained from measurements of the steady state and from the time course during ischaemia and reactive hyperaemia. Special signal processing, a microprocessor and a computer program facilitate the analysis of the data. They consider disturbances which come from a common tissue movement and from convulsions of the limbs. Measurements prove a decreased steady-state value and prolonged half-times during ischaemia and reactive hyperaemia when patients with peripheral arterial occlusive disease are compared with healthy subjects. PMID- 8205360 TI - Identification of lower arm motions using the EMG signals of shoulder muscles. AB - This investigation explored pattern recognition of EMG signals produced by shoulder area muscles to identify the performance of a select number of lower arm motions. The signals were modelled as fourth-order autoregressive processes with the parameters of the models used to classify the different motions. The recorded EMG signal was bandpass filtered for each individual to improve discrimination between signals. The method was shown to detect and identify EMG signatures produced by at least two, and sometimes three, different arm motions. Discrimination between the signal models for the motions was not affected by load variation or muscle fatigue. PMID- 8205361 TI - Determination of wrist kinematics using a magnetic tracking device. AB - The objective of this work is to present a method to determine the three dimensional kinematics of the human wrist joint under physiological loading conditions using a magnetic tracking device. Euler angles were used to determine wrist extension-flexion, radial-ulnar deviation and supination-pronation. The screw displacement axis (SDA) method was used to describe the relative motion between carpal bones. Computer graphics were also used to obtain a better visualization of the three-dimensional motions of the carpal bones. This was accomplished by combining motion data and digitization data describing the geometry of the articular surfaces of the carpal bones. Geometric data included the locations of several points located on the articular surfaces forming the radio-scaphoid and radio-lunate joints. The SDA axes describing the motions of the capitate or the lunate or the scaphoid with respect to the radius during flexion-extension were found almost parallel to the medial-lateral direction. Translations along any SDA did not exceed 2 mm. One can thus consider the motion of each carpal bone as a pure rotation about a screw axis. Also, the SDA axis describing the motion of the capitate with respect to the radius was found to pass through the proximal end of the capitate. The graphical display of carpal motions shows that, as the wrist is flexed, the surface of the lunate within the radio-lunate articulation moves from palmar to dorsal. On the other hand, the palmar-dorsal location of the proximal surface of the scaphoid within the radio scaphoid articulation remains almost unchanged. PMID- 8205362 TI - CO2 control of breathing: parameter estimation and stability evaluation. AB - A method is developed to evaluate system stability for the CO2 control of breathing in individuals by using data from the dynamics of CO2 rebreathing and elimination. The theoretical basis of the method is a physiological model of the CO2 respiratory control system and an explicit stability index (SI). The SI is algebraically related to the model parameters: system volume (Vs), cardiac output (Q), circulatory transit time (ts), and controller gain (G). A sequential optimization scheme is shown to yield estimates of the model parameters by comparing the alveolar ventilation and PCO2 of the model output with corresponding experimental data. Model simulation of CO2 rebreathing and elimination with different parameter values demonstrate that all parameters except ts have significant effect on the outputs. Least-squares estimation of the parameters using model-generated data with added noise showed good precision for all parameters (except ts). This analysis is performed with parameter values chosen to produce overdamped and underdamped responses that would occur in normal and abnormal respiratory control systems, respectively. It is anticipated that SI values of the (overdamped) normal and (underdamped) abnormal systems differ by much more than the variation produced by imprecision of the parameter estimates. For this circumstance, the method is expected to be sensitive enough to distinguish normal from abnormal CO2 respiratory control of individual subjects. PMID- 8205363 TI - Automatic fracture reduction with a computer-controlled external fixator. AB - The reduction of fractures by means of an Ilizarov's fixator is obtained by successively shortening or lengthening the rods. This entails that all reduction operations of the fracture stumps be performed with a series of empirical attempts, requiring great experience and manual dexterity in the surgeon. Moreover this process involves a long exposure of both physician and patient to potentially harmful radiation due to the continuous checking of the intermediate positions on the X-ray image intensifier. In order to overcome these limits a new device has been conceived, based on the application of three stepper-motors on three-rods. Its basic principle is functionally very similar to Ilizarov's prototype. The relative motions between the two frames are carried out by controlling the three actuators with a computer, which processes the number of required steps on the basis of an algorithm, starting from a few inputs supplied by the surgeon. This article illustrates the functional kinematic study necessary for the complete automation of the reduction process. Also considered is the complex problem of the reduction trajectory definition, intended as a sequence of configurations of partial correction, obtained by formalizing in geometrical terms the empirical criteria followed by the orthopaedic surgeon in reducing fractures. Such a sequence is intended to be a suggestion for the surgeon who can visualize and possibly interact with the system to determine a trajectory harmless for the soft tissues surrounding the bone. PMID- 8205364 TI - The effects of vertical and horizontal vibrations on the human body. AB - Vertical and horizontal vibrations of a 100 kg human have been investigated. A new mechanical model has been developed, and an analogous electric simulation has been carried out, which in turn has been analysed by using computer software (MICRO-CAP II). The vibration force comes from (a) hand, (b) seat and (c) combination of the two. The theoretical results obtained have been tabulated and are presented in a graphical manner. It has been found that the body segments (lower arm, head, torso, cervical spine and lumbar spine) are affected by horizontal vibrations when the input force (F(i)) comes from both hand and seat more than when (F(i)) comes from the seat alone. Similar results have been found also for the case of the lower arms and torso when the body is subjected to vertical vibrations. The head is affected by vertical vibrations when (F(i)) comes from the seat more than when (F(i)) comes from both hand and seat. An experimental set-up has been designed and measurements of vibrational signals from the human lower arm, head and torso have been carried out. Similar trends are shown for both theoretical results and experimental findings. PMID- 8205365 TI - Sensitivity functions of a human head movement model. AB - With time as the criterion to be optimized, the divergences from optimal head movements show systematic differences of their control signal variables with respect to single behaviours. To clarify these relationships, this study uses manipulation and mathematical analysis of the 6th order nonlinear head movement model, i.e. the threefold approach of sensitivity analysis. In addition to sensitivity coefficients, graphs and trajectories sensitivity functions have been analysed. This is the sensitivity of a nominal head movement to changes of the model parameters during the time course of the movement. This demonstrated both the specific change of the visco-inertial properties of the head movement model during the movement and also the potential pathological deficits that may occur. PMID- 8205366 TI - Manual or automatic nulling DC offset for physiological DC amplifier. AB - An inexpensive circuit to compensate for DC offset is presented. The circuit may be connected in a straightforward manner to any currently existing DC isolation amplifier and causes no deterioration in the performance of the system. The offset voltage is measured at discrete time intervals and then subtracted from the input signal. A switch is provided to bypass the offset compensation when the latter is not required. PMID- 8205367 TI - A scientist's view of bioengineering. AB - So, to summarize: my themes in this lecture have been: 1. Bioengineering is a many-splendoured thing. 2. There are few differences in principle between scientists and engineers, and they need to work together and respect one another's special contribution. 3. The Department of Health has done much to enhance your career structure and prospects recently; now you have to help us to polish your image even further. 4. There is urgent need for collaboration amongst all parties if we are to counter some potentially deleterious effects of the recent NHS reforms on the work of clinical scientists and engineers. Finally, I wanted to thank you for admitting me, just a little way, into the magical world of biological engineering. Life has become infinitely more exciting since you did so, and I owe you all a considerable debt of gratitude. PMID- 8205368 TI - A desk-top computer model of the circulatory system for heart assistance simulation: effect of an LVAD on energetic relationships inside the left ventricle. AB - The study of the interaction between a pneumatic left ventricle assist device (LVAD), driven with different control strategies, and the cardiovascular system is the subject of this paper. It is performed by a modular numerical model of the cardiovascular system connected to a numerical model of the LVAD. The circulatory system is simulated by a lumped parameter numerical model. The ventricle is represented by a time-varying elastance model to reproduce the Starling law of the heart. The effect of the LVAD on the cardiovascular system is evaluated, on the left ventricle alone, by an open-loop circuit consisting of the models of the ventricle, the LVAD and the arterial tree. The analysis is performed in terms of energy variables (such as external work and oxygen consumption and cardiac mechanical efficiency versus control strategy. The LVAD is driven by different control strategies: a fixed heart rate (with different delays from the onset of the natural ventricle contraction) and a variable heart rate. PMID- 8205369 TI - Early effects of cardiovascular drugs--do they predict clinical outcomes? AB - Indicators such as lowering of blood pressure in hypertension, alleviation of chest pain in angina pectoris, improvement in rest or exertional dyspnea from congestive heart failure (CHF) and suppression of ventricular arrhythmia are widely used in the management of cardiovascular diseases. There are often strong associations between the physiological indicators and the long-term clinical outcomes of cardiovascular disease such as stroke, myocardial infarction, sudden death and all-cause mortality. Physicians have assumed reasonably that early improvements in physiological markers will lead invariably to better long-term clinical outcomes. In recent years, a number of large clinical trials have demonstrated that short-term physiological improvements are not necessarily linked to better long-term clinical outcomes, but may be associated with less benefit than expected or even with detrimental outcomes. Management of cardiovascular diseases is complicated by the possibility that beneficial effects of a particular drug may be offset by its negative actions on the cardiovascular system. Effective antihypertensives may depress cardiac contractility; inotropes enhance left ventricular contractility in CHF, but may increase the risk of serious ventricular dysrhythmia; drugs which suppress ventricular arrhythmia may precipitate CHF or even excite pro-arrhythmic effects. Physicians must be conscious of this interplay of potentially beneficial and deleterious effects when cardiovascular drugs are prescribed. It is important in the analysis of large clinical trials of cardiovascular drugs to identify those situations in which the drug exhibits more benefit than harm and to determine, if possible, those aspects of drug action, drug dosage and population characteristics which contribute to the beneficial and detrimental actions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205370 TI - Methotrexate serum binding in rheumatoid arthritis. AB - The serum binding of methotrexate was determined by equilibrium dialysis using radiolabelled methotrexate. Methotrexate was only albumin-bound in serum. The binding was 46% in controls versus 42% in rheumatoid arthritis and 44% in cancer. Serum binding was significantly decreased by salicylate and high concentration of naproxen. Hypoalbuminemia and concomitant administration of salicylate or naproxen may influence methotrexate toxicity. PMID- 8205371 TI - Effect of 2,3-diphosphoglycerate on O2-dissociation kinetics of hemoglobin and glycosylated hemoglobin using the stopped flow technique and an improved in vitro method for hemoglobin glycosylation. AB - Studies under equilibrium conditions have shown that the oxygen affinity of hemoglobin (Hb) is lowered by 2,3-diphosphoglycerate (2,3-DPG), the physiological allosteric effector in erythrocytes, and enhanced by glycosylation of Hb. The kinetics of oxygen release, as a function of 2,3-DPG and the degree of glycosylation have been determined using the stopped flow method and a new in vitro glycosylation procedure allowing adequate amounts of functionally intact hemoglobin to be obtained. The rate constant k of O2-dissociation in glycosylated Hb (8% HbA1c) was approximately 10% lower than in native Hb (4% HbA1c). The addition of 2,3-DPG in concentrations up to 20 mmol/l resulted in a progressive increase of k from 61.5 +/- 3.3 s-1 to 65.3 ae 4.1 s-1 for native Hb and from 56.8 +/- 5.2 s-1 to 59.4 +/- 4.1 s-1 for glycosylated Hb. We conclude that (a) the degree of glycosylation similar to that found in diabetic patients is responsible for a significant decrease of the oxygen dissociation velocity and (b) 2,3-DPG concentration similar to those occurring in vivo have only a weak effect on the oxygen dissociation velocity. PMID- 8205372 TI - A graphical nomogram method for predicting toxic concentrations of unbound phenytoin. AB - The graphical nomogram method to estimate the phenytoin free concentration at any selected total serum phenytoin and/or albumin concentrations was applied using Scatchard binding equation. The binding parameters were calculated by the non linear least-squares regression analysis of the binding data collected from 96 outpatients on common anticonvulsant therapy. Free phenytoin concentration was measured by the Amicon multi-micro ultrafiltration system. The mean values of N and Kapp were found to be: N = 1.03, and Kapp = 18,500 (M-1). Correlation coefficient for relationship between measured and predicted free phenytoin concentrations was very good (r = 0.94), but the results of prediction-error analysis (MPE = 0.153, and RMSE = 0.296) show that the nomogram method overpredicts the measured free phenytoin (PHT) concentration approximately about 10% higher (15-30 mg/l) than serum phenytoin levels. PMID- 8205373 TI - Pharmacogenetics of desipramine metabolism. AB - There is wide interindividual variation in steady-state plasma concentration of desipramine and other tricyclic antidepressants primarily due to differences in rates of hydroxylation. Several studies have shown that the rate of hydroxylation of desipramine is correlated with the rate of hydroxylation of the genetic probe drug, debrisoquine, which is controlled by monogenic inheritance. However, no population studies of the polymorphic metabolism of antidepressants have been reported. In this study, 59 patients with endogenous depression received a fixed dose of desipramine and the steady-state plasma concentration of desipramine and 2-hydroxydesipramine were determined by high-pressure chromatography. A new statistical approach based on optimizing the fit to a specific stochastic model was utilized to separate the mixture of the three genotypes: homozygous extensive (AA), heterozygous extensive (Aa) and poor (aa) metabolizers. The proportions of the genotypes are 0.43, 0.45 and 0.12, respectively. The gene frequency of the low-activity allele is 0.34 and that of the high-activity allele is 0.66. The means (SD) of the desipramine/2-hydroxydesipramine metabolic ratios of the three genotypes are 1.71 (0.44), 3.32 (1.68) and 23.32 (10.03). These data suggest that the heterozygous genotype has half the metabolic activity of the homozygous extensive metabolizer and that the poor metabolizer genotype has negligible metabolic activity. PMID- 8205374 TI - Comparative bioavailability of two suspension formulations of potassium diclofenac in healthy male volunteers. AB - The bioavailability of two suspension formulations of potassium diclofenac (Flogan, Merck and Cataflam, Ciba-Geigy) were compared in eighteen healthy male volunteers who received a single dose of 7 ml of each suspension (equivalent to 105 mg of potassium diclofenac) in an open randomized two period crossover design, with a fourteen-day washout period between doses. Serum samples were obtained over a 24 hour interval and diclofenac concentrations were determined by HPLC with ultraviolet detection. From the serum diclofenac concentration vs time curves, AUC[0-24] (area under the concentration vs time curves from 0-24 h), Cmax (maximum achieved concentration), Tmax (time to achieve Cmax) and Ke (terminal first order elimination constant) were obtained. Overlapping of Tmax intervals for both formulations was observed, but the important inter-subject variation observed in Cmax ratios did not allow equivalence conclusion for the rate of absorption. Equivalence in the extent of bioavailability between both potassium diclofenac suspension brands was concluded from the analysis of AUC[0-24] ratios. PMID- 8205375 TI - Gastrointestinal manifestations of cocaine addiction. AB - Cocaine is one of the illicit hallucinogenic drugs which can be conveniently taken without resorting to parenteral administration. Almost all organs systems in the body are affected by its abuse. Complications involving the nervous, cardiovascular and reproduction systems have recently been published. In this report, complications relating to gastrointestinal system are reviewed. Acute ischemic syndromes are the most prominent gastrointestinal complication of cocaine use. Severe ischemia results from intense activation of alpha-adrenergic receptors in the mesentery. This ischemia results in gastropyloric ulcerations, gangrene and perforation of small as well as large intestine and colitis. Sudden collapse and deaths have been reported in "body packers" who swallow cocaine filled condoms in an effort to smuggle the drug through the customs. Several cases of acute hepatotoxicity and hepatocellular necrosis from cocaine use have also been reported. PMID- 8205376 TI - Enalapril pharmacokinetics and ACE inhibition, following single and chronic oral dosing. AB - Twelve normal volunteers were given 10 mg enalapril maleate by single and 2 weeks multiple dose administration, and blood samples were collected for the determination of enalaprilat concentration and angiotensin converting enzyme (ACE) activity. The mean terminal elimination half-life following a single administration of 10 mg enalapril, was 27 hours. The inhibition of ACE activity paralleled enalaprilat concentrations following both single and multiple dosing and the time of maximum inhibition of ACE activity was associated on both occasions with maximum concentration of enalaprilat. Emax modelling of enalaprilat concentration and ACE activity gave comparable values of Emax for both methods of administration. An accumulation factor of 1.7 was calculated from the area under the concentration time curve (AUC) of enalaprilat within a dosing interval at steady-state and the total AUC following single administration of enalapril. There were no significant differences between males and females in the accumulation factor, half-life and AUCinf. PMID- 8205377 TI - Pharmacovigilance in Germany. PMID- 8205378 TI - Concurrent identification of calpains I and II from chicken skeletal muscle. AB - A single anion-exchange column resolved two peaks of calcium-activated neutral protease activity, corresponding to the two calpain forms chicken skeletal muscle. Multiple columns have previously been needed to resolve the two isoforms from avian tissue. Calcium requirement assays confirmed one form to require approximately 100 microM Ca2+ for half-maximal activity, while the other required approximately 500 microM Ca2+. Electrophoresis revealed that the enzymes were not purified to homogeneity. PMID- 8205379 TI - Lipid biosynthesis by axenic strains of Blastocystis hominis. AB - Axenic strains of Blastocystis hominis incorporated 32P, added to the medium as orthophosphate, into a number of phospholipids, including sphingomyelin, cardiolipin, phosphatidic acid, the phosphoglycerides of choline, ethanolamine, serine, and inositol and some other minor phospholipids. Radioactive palmitate and glycerol provided in the growth medium introduced radiolabel into diacylglycerols, triacylglycerols, and all major phosphoglycerides found in the organism. Palmitate is a major fatty acid of cholesterol esters in B. hominis, but radioactive palmitate did not enter the cholesterol ester pool. Radioactive acetate was not incorporated into any lipids. Cholesterol and cholesterol esters of the organism were not labeled when cells were grown in the presence of radioactive glucose, mevalonic acid, or mevalonolactone. Radioactive cholesterol added to the medium became stably associated with B. hominis cells, but none of the radioactive cholesterol entered the cholesterol ester pool. Cholesterol-[3H] palmitate added to the medium became stably associated with the organism, and most of the radioactivity associated with the cells remained in the cholesterol ester fraction on extended incubation. These results show that this parasitic protozoan has the capacity to synthesize most cellular lipids de novo, but suggest that it acquires free cholesterol and intact cholesterol esters directly from growth medium. PMID- 8205380 TI - Inactivation of chemotactic peptides by aminopeptidase Ey from hen's (Gallus gallus domesticus) egg yolk. AB - Aminopeptidase Ey, purified from hen's (Gallus gallus domesticus) egg yolk, was studied for its specificity against N-blocked peptides. Only N-formylmethionyl peptides were hydrolyzed by the enzyme in the tested peptides. N-Formyl-methionyl leucyl-phenylalanine (fMet-Leu-Phe) lost its chemotactic activity toward human neutrophil after incubation with aminopeptidase Ey. PMID- 8205381 TI - Purification, characterization and partial sequencing of the heart fatty acid binding protein from Bufo arenarum. AB - A 15.7 kDa fatty acid-binding protein from toad heart was purified by gel filtration chromatography on Sephadex G-75 followed by anion-exchange chromatography on a Mono-Q column. Purity was confirmed by gel electrophoresis and isoelectric focusing. Molecular mass, isoelectric point, amino acid composition and partial internal sequence showed that the protein is related to mammalian heart fatty acid-binding proteins. PMID- 8205382 TI - Electrophoretic and morphometric evidence for two species of the genus Rana (Amphibia, Ranidae) and some aspects of their variabilities. AB - Frogs of two species, genus Rana, R. mascareniensis and R. levantina from northern Egypt, were examined using electrophoresis for 15 presumptive loci and measuring of 11 morphological characters, employing discriminate and principle component analysis. Electrophoretic and morphometric data showed clear interspecific differences. Using serum and tissue electrophoresis all individuals of R. mascareniensis had no intraspecific variabilities but R. levantina showed some intraspecific variabilities. PMID- 8205384 TI - Comparative Biochemistry & Physiology B bibliography. PMID- 8205383 TI - Casein and tyrosine kinase activities of developing chick embryo liver. Effect of triiodothyronine. AB - Cytosol cAMP-independent quercetin-inhibited protein kinase of developing chick embryo liver was measured at three embryonic ages (days 12, 14 and 18) in the presence of casein and poly (Glu-Na, Tyr) 4:1 as substrates. In the early embryonic stages the tyrosine kinase was almost as active as casein kinase, but on day 18 the tyrosine phosphorylation was only 25% of the casein phosphorylation. Both kinase activities strongly increased by the end of embryonic development: 7-fold with casein and 2.6-fold with poly (Glu-Na, Tyr) 4:1. Triiodothyronine caused twice the stimulation of casein and tyrosine phosphorylation on day 12, but had no effect on day 18. PMID- 8205385 TI - Progress in understanding the Drosophila dnc locus. AB - The genetic dissection of learning and memory in Drosophila is two decades old. Recently, a great deal of progress has been made towards isolating new mutants as well as towards a better understanding of the originally isolated ones. This paper reviews the recent developments in the understanding of the structure and function of the gene identified by the first and best-characterized of these mutants, the Drosophila dunce mutant. PMID- 8205386 TI - Glycerol phosphorylcholine (GPC) and serine ethanolamine phosphodiester (SEP): evolutionary mirrored metabolites and their potential metabolic roles. AB - Water-soluble phosphodiesters (WSPDE) are a prominent feature of many 31P-NMR spectra; however, their role has remained somewhat of a mystery. What has been missed in almost all previous studies is the fact that two classes of WSPDE exist in vertebrates: those in mammals and those in the other (reptile-avian) line. The first is represented by glycerol phosphorylcholine and the second by serine ethanolamine phosphodiester. A further examination of the literature suggests a common role for all WSPDE as lysophospholipase inhibitors and therefore net sparers of phospholipids by decreasing phospholipid metabolic throughput. PMID- 8205387 TI - The effect of troponin C substitution on the Ca(2+)-sensitive ATPase activity of vertebrate and invertebrate myofibrils by troponin Cs with various numbers of Ca(2+)-binding sites. AB - The effect of four different classes of troponin C with different numbers of Ca(2+)-binding sites was investigated on the Ca(2+)-activation profiles of the ATPase of troponin C-depleted myofibrils prepared from vertebrate fast skeletal (rabbit), vertebrate cardiac (bovine) and invertebrate crustacean tail striated (crayfish, lobster) muscles. Troponin C from vertebrate sources [fast skeletal (rabbit, chicken) with four Ca(2+)-binding sites, and cardiac (bovine, chicken) with three Ca(2+)-binding sites] activated the Ca(2+)-ATPase of troponin C depleted myofibrils from the vertebrate skeletal or cardiac muscles, but did not activate the invertebrate troponin C-depleted crustacean myofibrils. On the other hand, two kinds of crustacean (crayfish, lobster) troponin C with two Ca(2+) binding sites activated only crustacean troponin C-depleted myofibrils. One invertebrate molluscan (Akazara scallop) troponin C with one Ca(2+)-binding site did not activate the Ca(2+)-ATPase of the troponin C-depleted myofibrils from either vertebrate or crustacean striated muscles. The results obtained from the four kinds of combinations of troponin C and troponin C-depleted myofibrils from vertebrate skeletal and cardiac muscles demonstrated that the characteristic cooperativity of the Ca(2+)-activation profiles of both vertebrate skeletal and cardiac myofibrils was determined by the skeletal or cardiac origin of troponin C molecules, irrespective of the animal species, and the Ca(2+)-affinity of the myofibrillar ATPase was related to the skeletal or cardiac origin of both the troponin C and myofibrils. These findings indicated that each of the four classes of troponin C has its own characteristic Ca(2+)-activation profile for each kind of myofibril examined in the present study. PMID- 8205388 TI - Purification and characterization of vitellin-2 from the ovary of the American cockroach, Periplaneta americana. AB - Two vitellins (Vn-1 and Vn-2) were identified in cockroach ovary. Vn-2 was purified by ion-exchange chromatography using DEAE cellulose and Sepharose CL-6B, and gel filtration using Sephadex G-200 and Sepharose 4B. Vn-2 comprises three subunits with molecular weights of 102, 72 and 40 kDa. Vn-2 contains diacylglycerol and triacylglycerol; their fatty acids are mostly lauric acid and palmitoleic acid. Vn-2 also has phosphatidylcholine and phosphatidylethanolamine but no sphingomyelin. Vn-2 contains large amounts of glutamic acid and aspartic acid but small amounts of tyrosine, phenylalanine, and methionine. Vn-2 gradually decreases during embryonic development; none remains in first instar larvae. It was found that Vn-2 partially reacted immunologically with ovarian extracts of Periplaneta fulginosa but not with those of Blattella germanica. Vn-2 also showed no immunological reaction with extracts from other orders; including Cletus schmidti (Hemiptera), Lucilia illustris (Diptera), Anechura japonica (Dermaptera), Bombyx mori (Lepidoptera), and Ducetia japonica (Orthoptera). PMID- 8205389 TI - The 9-kDa calbindin gene of Rousettus aegyptiacus: its identification and isolation from a genomic library. AB - A genomic library of the fruit bat (Rousettus aegyptiacus) was constructed in lambda phage gt11. The titre of the library was determined to be 2 x 10(5) pfu/ml. The genomic library was amplified and the titre of the amplified library increased 300-fold to 7 x 10(7) pfu/ml. The library was screened by in situ hybridization techniques using a fragment of the mouse 9-kDa calbindin cDNA as a probe. Screening of 10(5) plaques yielded a positive clone. Three additional rounds of screening were performed to purify the positive. Lambda phage DNA was isolated from the positive clone and restriction digest analysis, followed by hybridization studies, was performed on these digests in order to determine the location of the bat 9-kDa calbindin gene in the insert of the lambda phage vector. Restriction maps so derived were interpreted from the published sequence for the rat 9-kDa calbindin gene and indicate the successful isolation of the 9 kDa calbindin gene of Rousettus aegyptiacus. PMID- 8205390 TI - Oxygenation of unsaturated fatty acids by hepatic microsomes of musk shrew (Suncus murinus). AB - The cytochrome P-450-dependent monooxygenase in musk shrew (suncus; Suncus murinus) liver microsomes metabolized unsaturated fatty acids (oleic, linoleic, alpha-linolenic and arachidonic acids) to a variety of oxygenated products. alpha Linolenic acid was the most active substrate. The oxygenation activity increased with an increase in the number of cis double-bonds in the C18 fatty acids. This suggests that the introduction of cis double-bonds in C18 fatty acids is important for the binding of cytochrome P-450 in suncus liver microsomes. Regioselectivity of arachidonic acid oxygenation was observed in suncus liver microsomes; rat liver microsomal cytochrome P-450 generated epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acid as major products while the cytochrome P 450-dependent monooxygenase in suncus liver microsomes yielded omega- and (omega 1)-hydroxyarachidonic acids as major reaction products. PMID- 8205391 TI - Immunochemical characterization and cellular distribution of protein kinase C isozymes in the bovine corpus luteum. AB - Research was conducted to determine the nature of the isoforms of protein kinase C (PKC) present in the bovine (Bos taurus) corpus luteum (CL) and their subcellular distribution. Western blot analysis was performed using isozyme specific polyclonal antibodies and revealed that the bovine corpus luteum contains the alpha and epsilon isozymes of PKC, but not the beta, gamma, delta or zeta isozymes. Subcellular fractionation demonstrated that the alpha and epsilon isozymes of PKC were present in both the cytosolic and plasma membrane fractions. Densitometric measurements of Western blots of the subcellular luteal PKC fractions indicated that PKC alpha was found predominantly in the cytosolic fraction, whereas the majority of PKC epsilon was associated with the plasma membrane. PMID- 8205392 TI - Purification and properties of caldesmon-like protein from molluscan smooth muscle. AB - In this comparative study, the heat-stable protein content of scallop muscles was reinvestigated. The hCaD-like protein was prepared and its properties carefully examined. The heat-stable high-molecular-mass caldesmon-like (hCaD-like) protein is only present in the catch (smooth) muscle and it is completely absent in the striated muscle of scallop. The isolated scallop hCaD-like protein cosediments with F-actin, binds to myosin significantly and inhibits the ATPase activity of acto-myosin. A partial cDNA clone from a Mytilus anterior byssus retractor muscle (ABRM)-related protein showed strong homology with the hCaD gizzard sequence. This allowed identification of the heat-stable 100-110 kDa protein doublet band isolated in this study as a caldesmon-like molecule. PMID- 8205393 TI - Hybridization of matrix-bound MM-creatine kinase with BB-creatine kinase and arginine kinase. AB - Dimeric rabbit muscle creatine kinase (MM-CK) was bound to CNBr-activated Sepharose 4B by one of its subunits (MM-CKA). Treatment of MM-CKA with guanidine hydrochloride released the unbound subunit to yield the matrix-bound monomer (M CKB). M-CKB recombined with dissociated MM-CK soluble subunits to reconstitute a matrix-bound dimer (MM-CKC). M-CKB also associated with dissociated subunits of BB-CK from crude extracts of rabbit brain and of arginine kinase from sea cucumber muscle (MM-AK) to form the matrix-bound heterohybrids MB-CKC and M-CK/M AKC, respectively. Guanidine hydrochloride gradient elution studies showed that MM-CKA, MM-CKC and MB-CKC were all dissociated at the same concentration of the denaturant (0.96 M), while the M-CK/M-AKC heterohybrid was less stable, dissociating at 0.5 M. The specific interaction between subunits of echinoderm and mammalian phosphagen kinases to form a hybrid enzyme of dual substrate specificity supports the view that these enzymes had a common evolutionary origin. PMID- 8205394 TI - Isolation and characterization of tropomyosin from fish muscle. AB - A comprehensive survey of tropomyosin from various fish myotomal muscles is reported. The fish tropomyosins were blocked at the N-terminus and, as expected, were found to be of similar amino acid composition, alpha-helical content (> 90% at 10 degrees C) and molecular weight to other vertebrate striated muscle forms. The tropomyosins of salmonids and herring muscle were noticeably heterogeneous when assessed by 2D-PAGE. The distribution of isoforms was tissue-specific: slow muscle contained alpha-type tropomyosin while fast muscle contained beta-type tropomyosin. In other species (cod, haddock, wolf-fish and sharks) alpha-type tropomyosins were present in both kinds of muscle but beta-tropomyosin was absent. PMID- 8205395 TI - Auto-antigens in rheumatoid arthritis--a new candidate? PMID- 8205396 TI - Contracting in rheumatology. PMID- 8205398 TI - Interleukin-8 secretion and 15-lipoxygenase activity in rheumatoid arthritis: in vitro anti-inflammatory effects by interleukin-4 and interleukin-10, but not by interleukin-1 receptor antagonist protein. AB - We have examined the ability of interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-1 receptor antagonist protein (IL-1ra) to regulate spontaneous interleukin-8 (IL-8) production in cultured SF mononuclear cells (SFMC) from RA. Furthermore, we examined whether IL-4, IL-10, or IL-1ra could influence the production of the arachidonic acid products leukotriene B4 (LTB4), 12-hydroxy eicosatetraenoic acid (12-HETE) and 15-hydroxy-eicosatetraenoic acid (15-HETE). IL-4 induced a maximal suppression of 75% in the IL-8 secretion in SFMC from 10.0 ng/ml down to 2.5 ng/ml after 24 h and from 17.2 ng/ml to 4.2 ng/ml after 72 h of culture. IL-10 induced a 55% inhibition of the IL-8 secretion at 24 h and a 40% inhibition at 72 h. IL-1ra did not change the spontaneous IL-8 secretion from rheumatoid SFMC. We also examined, whether addition of IL-4, IL-10 or IL-1ra was able to modulate formation of the arachidonic acid products LTB4, 12-HETE and 15 HETE in cultured SF cells, stimulated with the calcium ionophore A23187. 15-HETE was not detected in untreated cultures, nor in IL-10 or IL-1ra treated cultures. IL-4, however, stimulated the formation of the anti-inflammatory mediator; 15 HETE (23 ng/10(6) cells). These results suggest that IL-4 or IL-10, could have beneficial anti-inflammatory effects in RA. PMID- 8205397 TI - Lamellar bodies in synoviocytes, mesothelium and specific epithelia as possible site of auto-antigen in rheumatoid disease. AB - Intracytoplasmic lamellar organelles identical in ultrastructure to surfactant containing lamellar bodies found in type II pneumocytes, have been demonstrated in other tissues, in synoviocytes and mesothelial cells, in a distribution pattern which reflects the systemic expression of rheumatoid disease. Antibodies raised against surfactant protein A (SP-A), exhibit a ranking of tissue reactivity in area, intensity and density of cells which also parallels the frequency and degree of pathological involvement characteristic of rheumatoid disease, showing in ascending order of immunopositivity, lacrymal and salivary epithelia, pulmonary parenchyma, mesothelium and synoviocytes. Maximal tissue reactivity to anti-SP-A antibodies was found in the synovium of 55 rheumatoid patients exhibiting classical histopathological appearances of RA, in a pattern of immunostaining identical to that obtained with ML30, an antibody to mycobacterial heat shock protein 65kDa which, in turn, cross-reacted with SP-A in dot blot testing. PMID- 8205399 TI - Effect of exogenous erythropoietin on haem synthesis in anaemic patients with rheumatoid arthritis. AB - The effect of recombinant human erythropoietin (rHuEPO) on haem biosynthesis in peripheral red blood cells was evaluated in 12 patients with RA and anaemia (mean haemoglobin concentration 102 g/l, range 90-109 g/l). Before treatment, the serum concentrations of erythropoietin (EPO) were low (mean 13 pmol/l, range 5-32 pmol/l), the activities of haem-synthesizing enzymes within the reference intervals and the erythrocyte protoporphyrin (E-PROTO) concentrations clearly higher than normal. Nine patients responded with an increase in the haemoglobin level of 15 g/l or more. rHuEPO induced a rise in the mean haem synthase (HAEM-S) activity from a baseline of 12.1 to a maximum of 26.8 pmol/h per 10(6) reticulocytes after 20 weeks of treatment (P < 0.002). The mean E-PROTO concentration also rose and reached its maximum at 8 weeks of treatment. We conclude that correction of anaemia in patients with RA using rHuEPO is associated with an activation of HAEM-S, commonly regarded as the rate-limiting enzyme of haem synthesis in erythroid cells. Functional iron deficiency probably explains the simultaneous rise in E-PROTO concentration. PMID- 8205401 TI - Longitudinal bone mineral density changes in early rheumatoid arthritis. AB - A prospective longitudinal study of patients with early RA was performed to examine the influence of disease duration, disease activity and physical activity on bone loss. Sixty-seven patients with non-steroid treated RA of less than 5 yr duration, including 16 patients with disease duration less than 6 months, had BMD measurements of the femoral neck and the lumbar spine over a 12-month period using dual energy X-ray absorptiometry. The BMD changes were compared with values from 72 control patients and were also correlated with serial measurements of disease activity (measured by the Stoke Index) and disability [measured by the Health Assessment Questionnaire (HAQ) score], at 3-monthly intervals over the 12 month period. No significant differences in BMD changes were found between RA patients and controls overall. Patients with disease duration of less than 6 months had significantly greater loss of BMD at the femoral neck (-3.9%, S.E.M. 1.5) than the remainder of the cohort (-0.2%, S.E.M. 0.7) (P = 0.02) and controls (-0.8%, S.E.M. 0.6). Lumbar spine BMD changes correlated with the initial Stoke Index (Rs-0.373, P = 0.01) but not mean Stoke Indices. There was no correlation of BMD changes with age or HAQ scores. These findings suggest that significant bone loss occurs within the first few months of disease in patients with RA. PMID- 8205400 TI - Suppression of adjuvant-induced arthritis by liposomally conjugated methotrexate in the rat. AB - A phospholipid conjugate of methotrexate was synthesized and liposomally formulated in order to determine whether such a formulation could modulate the severity of experimentally induced arthritis in the rat. Lewis rats were immunized with Mycobacterium butyricum and after the onset of joint inflammation were treated intravenously with methotrexate liposomes (MTX-LIPO). This preparation was significantly better in reducing established joint inflammation than comparable doses of the free drug or empty liposomes of identical lipid composition. Haematopoietic toxicity associated with MTX-LIPO was significantly less than seen with comparable doses of the free drug. PMID- 8205402 TI - Post-menopausal vertebral osteoporosis: can dual energy X-ray absorptiometry forearm bone density substitute for axial measurements? AB - This study compared measurements of BMD using dual energy X-ray absorptiometry (DXA) at three sites in the nondominant forearm (ultradistal, distal one-third and a mid-region between these two), the lumbar spine (L1-L4) and the proximal femur (femoral neck, trochanter and Ward's triangle) for the evaluation of vertebral osteoporosis. Studies were performed on 100 normal women aged 29-69 yr (average 52 yr) and 63 osteoporotic women age 48-75 yr (average 66 yr) using the Hologic QDR-1000. Precision values of < 1% were obtained in both normal and osteoporotic women at both forearm and axial sites. Z-scores for the osteoporotics [Z = (mean BMD normal--mean abnormal)/S.D.] were--2.02 lumbar spine, -1.96 femoral neck, -1.79 ultradistal forearm, -1.73 mid region and -1.66 distal one-third forearm. Receiver operating characteristic curves showed that the lumbar spine and femoral neck equally discriminated between normals and osteoporotics with a 95% area under each curve, significantly greater values than those for the forearm which were 87% ultradistal, 89% mid forearm and 86% distal one-third forearm. Fracture thresholds, defined as the 90th centile of BMD for osteoporotic patients, were 1 S.D. below the normal mean for lumbar spine and femoral neck but equal to the mean for ultradistal, 0.6 S.D. below mean for mid region and 0.3 S.D. below mean for distal one-third region. We conclude that for the discrimination of normals and osteoporotic women the three forearm sites are comparable. However, both lumbar spine and proximal femur BMD are superior to all forearm sites. PMID- 8205403 TI - Alpha 1-antichymotrypsin, C-reactive protein and erythrocyte sedimentation rate in polymyalgia rheumatica and giant cell arteritis. AB - Forty-four patients with polymyalgia rheumatica and/or giant cell arteritis (PMR/GCA) were followed from presentation, through remissions and relapses for a median duration of 36 months. Clinical disease activity, ESR, CRP and alpha 1 antichymotrypsin (alpha 1-ACT) were measured. Before treatment ESR, CRP and alpha 1-ACT were all significantly raised, compared with age- and sex-matched controls. On clinical remission with prednisolone treatment, ESR and CRP fell to control levels but alpha 1-ACT behaved quite differently, remaining raised for 18 months or until prednisolone treatment could be withdrawn. At 18 month follow-up of PMR/GCA, and alpha 1-ACT level of < or = 0.7 g/l was associated with a reduced risk of subsequent relapse (P = 0.006). At clinical relapse during treatment, ESR was not raised compared with controls, and CRP, although significantly higher than controls (P = 0.015), remained less than 6 mg/l in the majority of patients. The three laboratory investigations were, therefore, of limited value in confirming relapses of PMR/GCA during prednisolone treatment, but alpha 1-ACT may be useful as an indicator of underlying disease activity and hence as a guide to the speed that the prednisolone dosage should be reduced. PMID- 8205404 TI - Changes in stiffness following short- and long-term application of standard physiotherapeutic techniques. AB - A computer-controlled MCP joint arthrograph was developed to measure the stiffness of finger joints objectively. This was used to study the short-term (one application) and long-term (multiple applications over 6 weeks) effects of several physiotherapeutic methods on the reduction in joint stiffness. The techniques used were hot wax baths, pulsed ultrasound alone, wax baths plus pulsed ultrasound and exercise. In the short-term (i.e. after each application) wax plus ultrasound produced a statistically significant reduction in elastic torque range (P < 0.01) and dissipated energy (P < 0.05). However, the reductions in these stiffness parameters were temporary. Long-term no significant reductions in stiffness were measured. In other words, stiffness was reduced by each therapy session, but it then increased again before the next session. Wax, ultrasound alone or exercise produced no short- or long-term effects. PMID- 8205405 TI - Consistency of morning stiffness: an analysis of diary data. AB - This study aimed to determine the within-individual daily variation in morning stiffness (MS) of RA patients, and to validate the routine clinically derived duration of MS against that recorded prospectively by patients. Forty-nine RA patients, who during a detailed clinical interview reported experiencing MS that week were studied. They were asked to prospectively record, using a diary, daily information on the duration of their MS. The times both of waking and of getting up were noted, as well as the times to first improvement, maximum improvement and complete disappearance of MS, providing six possible estimates of MS duration, three of which, using waking as starting points, could be compared with the interview. The daily variation of MS was assessed by the within-patient range. The median duration of the diary scores was then compared with the MS estimates recorded at the interview. There was a large intra-individual variation in duration of MS, whichever of the six definitions were used. Half of the patients recorded ranges of MS scores of 3 h or more within the same week. There was also marked variation between the median diary derived duration and that ascertained by interview. This variation was at its smallest when the duration of MS was calculated as time until maximum improvement. The routine recording of the 'typical' duration of MS seems to have little clinical value in the face of the large within-patient variation. Of the possible choices for estimating duration, the time from waking to maximum improvement appeared to be the best indicator of the average duration of MS in RA patients. PMID- 8205406 TI - Physician perceptions of the value of physical modalities in the treatment of musculoskeletal disease. AB - We randomly surveyed 100 specialists in rehabilitation medicine and 100 rheumatologists concerning their perceptions of the value of 11 different physical modalities--cold, active and passive exercise, interferential current, laser, magnetotherapy, microwave, shortwave diathermy, traction, ultrasound and transcutaneous nerve stimulation in the treatment of seven different musculoskeletal conditions--acute arthritis, joint contracture, neck pain, back pain, tendinitis, reflex sympathetic dystrophy and frozen shoulder. There were significant differences in the perceived benefits of modalities which varied by modality and condition. Overall, rehabilitation medicine specialists regarded modalities to be helpful more often than rheumatologists (P < 0.001). PMID- 8205407 TI - Vegetarian diet for patients with rheumatoid arthritis: can the clinical effects be explained by the psychological characteristics of the patients? AB - In a controlled, single blind clinical trial we have demonstrated recently a beneficial effect of fasting and vegetarian diet in RA. In the present study we compared 53 patients who participated in this clinical trial with 71 other RA patients with regard to some psychological parameters. The patients who participated in the clinical trial differed significantly from other RA patients. Firstly, they had a higher internal score and a lower chance score on the Multi dimensional Health Locus of Control Scale (MHLCS). Secondly, their belief in the effect of ordinary medical treatment, evaluated by a 10-cm visual analogue scale, was lower, and their belief in the effect of 'alternative', unconventional forms of treatment was higher. Of the patients who were randomized to a vegetarian diet, there was no significant difference between diet responders and diet non responders with regard to the MHLCS scores. But, diet responders had a significantly lower belief in the effect of ordinary medical treatment compared with diet non-responders. The psychological distress imposed on the patients by changing from an omnivorous diet to a vegetarian diet was monitored during the clinical trial by means of the General Health Questionnaire. Throughout the clinical trial, this variable favoured the vegetarians compared with the omnivorous and the diet responders vs the diet non-responders. We conclude, firstly, that patients with certain psychological characteristics were selected to the clinical trial; secondly, that the MHLCS scores could not explain the clinical improvement, but it may have been influenced by the patients' beliefs in ordinary and 'alternative' forms of treatment; and thirdly, that dietary treatment decreased psychological distress. PMID- 8205408 TI - Fluid retention syndrome and fibromyalgia. AB - Fluid retention syndrome (FRS) or idiopathic oedema is an unusual clinical entity almost exclusively seen in women, which remains under-diagnosed and poorly understood. It can produce a variety of symptoms ranging from headaches and blurring of vision to abdominal pains and diarrhoea [1]. More commonly it presents with symptoms of bloating, fatigue and generalized weakness. We describe four cases of FRS who presented to the rheumatology clinic with signs and symptoms of fibromyalgia. We also discuss the common features of these two conditions and argue that rheumatologists need to be aware of this condition. PMID- 8205409 TI - Acute inflammatory polyarthritis in association with tamoxifen. AB - The antioestrogen drug tamoxifen is widely used to treat breast carcinoma. We report three cases in which its use was temporally related to the development of an acute inflammatory polyarthritis resembling RA; a side-effect not previously reported. Possible mechanisms for such an effect are discussed. PMID- 8205410 TI - Henoch-Schonlein purpura remitting in pregnancy and during sex steroid therapy. AB - This paper reports on a 22-yr old female patient with recurrent bouts of Henoch Schonlein purpura since puberty occurring monthly at the time of menstruation. Remissions occurred during pregnancy, and on several occasions and in a dose responsive manner when the patient was prescribed birth control pills containing progesterone and oestradiol. Flares recurred when this therapy was discontinued. We hypothesize that this patient has an inflammatory disease involving neutrophil activation by excessive IgA, which is modulated by exogenous and endogenous sex steroids. It is unlikely that these hormonal influences are a common occurrence, but rather represent, in this case, a singular example of potential endocrine modulation of inflammatory disease. PMID- 8205411 TI - Hepatitis C virus associated with mixed cryoglobulinaemia. PMID- 8205412 TI - Mononeuritis in two patients with limited cutaneous systemic sclerosis. PMID- 8205413 TI - Gout in patients with systemic lupus erythematosus. PMID- 8205414 TI - Recurrent pericarditis and cardiac tamponade in rheumatoid arthritis: effectiveness of colchicine. PMID- 8205415 TI - Aneurysmal bone cyst--an unusual presentation of neck pain in a young adult. PMID- 8205416 TI - Birth order effect in rheumatoid arthritis. PMID- 8205417 TI - Magnetic resonance imaging of osteitis condensans ilii. PMID- 8205418 TI - Borderline lesions detected by breast screening. PMID- 8205419 TI - Short bowel syndrome: metabolic and surgical management. AB - The management of short bowel syndrome requires long-term nutritional support and monitoring, medication, and occasionally additional surgical procedures. Constant attention is required to ensure adequate adaptation of the gut. This article reviews the normal function of the small bowel, adaptation following resection, total parenteral and enteral nutrition, and the role of adjunctive surgical procedures in the management of short bowel syndrome. PMID- 8205420 TI - Malignant anal tumours. AB - Anal tumours represent 5 per cent of anorectal cancers and exist as two clinical entities: tumours of the anal canal and those of the anal margin. Smoking and sexual behaviour, particularly homosexual anal intercourse, are important aetiological factors. This association is related to anal warts and human papillomavirus infection, notably type 16, which is found in around 70 per cent of warts. Symptoms are non-specific and are frequently attributed to benign conditions. Rectal examination reveals a characteristically infiltrating lesion and any suspicious anal area should be biopsied. There are two histological types. Squamous carcinoma comprises approximately 95 per cent of anal tumours and includes the 35 per cent of tumours derived from the anal transition zone (cloacogenic tumours), containing a mixture of squamous and mucinous elements. The remaining 5 per cent of anal tumours are adenocarcinoma. Squamous cell tumours of the anal canal are probably best treated using radiotherapy (with chemotherapy) as complete response rates, 5-year survival rates, and incidences of normal sphincter function and significant toxicity are around 80, 70, 75 and 20 per cent respectively. Treatment failures may be salvaged by surgery. The 5 year survival and local recurrence rates for radical surgery are around 60 and 25 per cent respectively; there are few indications for local excision. In contrast, 60 per cent of anal margin tumours are suitable for local excision, the 5-year survival rate being in excess of 80 per cent. Combining radiotherapy with surgery may give additional benefit. Current randomized controlled trials should further clarify the relative merits and demerits of the treatment options. PMID- 8205421 TI - Ruptured aortic aneurysm: early postoperative prediction of mortality using an organ system failure score. AB - Ruptured abdominal aortic aneurysm (AAA) is a personal and public health catastrophe because of the high and unimproving mortality rate, increasingly long intensive care unit (ICU) stay and rising hospital costs. Criteria are needed to identify patients with a poor prognosis so that treatment and resources may be directed to those with a better outlook. This retrospective study reviews perioperative variables, outcome and length of ICU stay for 99 consecutive patients with operated ruptured infrarenal AAA between 1985 and 1992 who reached the ICU alive. Early death (within 48 h) occurred in 20 per cent using 24 ICU days and late death (after 48 h) occurred in 29 per cent using 420 ICU days; neither type of death could be predicted before operation. Multiple organ failure, the cause of 93 per cent of late deaths, was assessed for each patient 48 h after operation using an organ system failure score. There was a strong positive correlation between organ system failure score and mortality rate (P < 0.00001); all 20 patients with more than two failing organ systems died. If used in decision making the score would have saved 43 per cent of the ICU days associated with late mortality. Withdrawing postoperative treatment at an early stage in accordance with an organ system failure score may be a defensible and cost-effective option. PMID- 8205422 TI - Below-knee amputation using a medially based flap. PMID- 8205423 TI - Vein bypass surgery to the foot in patients with diabetes and critical ischaemia. AB - The feasibility of vein bypass surgery to the arteries of the foot was studied in a diabetic population with critical ischaemia; whether or not such reconstruction leads to an independent lifestyle was assessed 1 year later. Thirty-three reconstructions were performed on 32 limbs in 31 patients. The mortality and reoperation rates within 1 month were both 6 per cent. Primary and secondary patency, limb salvage and survival rates at 1 year were 76, 89, 89 and 82 per cent respectively. Good results in the form of combined survival, patency, limb salvage, walking ability, relief of pain and residence at home were achieved in 64 per cent of patients after 1 year. Reconstructive vascular surgery to the foot in diabetics is feasible and affords two-thirds of patients an independent lifestyle 1 year after surgery. PMID- 8205424 TI - Treatment and outcome of severe lower-limb ischaemia. AB - The overall outcome of severe lower-limb ischaemia in terms of limb salvage and mortality is poorly documented. A consecutive series of 232 severely ischaemic legs in 209 patients was therefore studied. An aggressive policy of revascularization has been pursued; this was attempted in 89 per cent of legs, with a primary amputation rate of 8 per cent. The perioperative 30-day limb salvage rate was 79 per cent with a patient mortality rate of 20 per cent. At 12 and 24 months the limb salvage rates were 74 and 71 per cent and patient survival rates 75 and 73 per cent respectively. To identify high-risk groups the effects on limb salvage and mortality of age, sex, presentation, diabetes and ankle systolic pressure of 50 mmHg or less were studied. Using life-table analysis, none of the preoperative risk factors had an effect on limb salvage and mortality. An aggressive policy of revascularization provides excellent results in the treatment of patients with severe leg ischaemia. PMID- 8205425 TI - Penetrating injuries of the subclavian vessels. AB - A study was made of 76 patients with subclavian vessel injury. The mechanism of trauma was stabbing in 40 patients (53 per cent) and gunshot in 36 (47 per cent). There were marked differences between the two groups in clinical presentation, operative management and outcome. The group with gunshot injury was characterized by a more immediate threat to life, and a greater need for a median sternotomy and use of interposition grafts. The mortality rate in patients with gunshot wounds was more than twice that in the group with stab injury. PMID- 8205426 TI - Effect of mode of application of papaverine on the contractile response of the internal mammary artery. AB - A study was performed to investigate the duration of action of papaverine applied either intraluminally or in a combined intraluminal and extraluminal fashion in vitro, and how the reactivity of the internal mammary artery (IMA) to a range of vasoconstrictors is affected. Segments of IMA exposed to only intraluminal papaverine (10(-4) mol/l) for 15 min recovered their contractile response to 90 mmol/l potassium chloride to pretreatment levels within 2 h. In contrast, combined intraluminal and extraluminal administration of papaverine resulted in a significant depression of the contractile response to 90 mmol/l potassium chloride (P < 0.001), which persisted for at least 5 h. Responses to 5 hydroxytryptamine, noradrenaline, the thromboxane mimetic U46619, histamine and dopamine were not significantly different between control tissues and those that had received intraluminal papaverine. The duration of action of papaverine is affected by its route of delivery and there are no significant short-term effects on the contractile mechanisms in the arterial wall after intraluminal administration. PMID- 8205427 TI - Extracranial carotid artery flow measurement during carotid endarterectomy using a Doppler ultrasonographic flowmeter. AB - A study was performed to evaluate immediate changes in carotid artery blood flow after carotid endarterectomy using a Doppler ultrasonographic flowmeter. Forty seven consecutive patients aged 49-78 (median 64) years with symptomatic internal carotid artery (ICA) stenosis underwent carotid endarterectomy. Volume flow, resistance and pulsatility index were measured in the common carotid artery (CCA) and ICA both before and after operation. ICA flow increased by 54 per cent (P < 0.01) and resistance decreased by 58 per cent (P = 0.01). CCA flow rose by 17 per cent (P = 0.1) and resistance fell by 21 per cent (P = 0.02). The pulsatility index did not change significantly. The Doppler ultrasonographic flowmeter offers a simple, non-invasive and convenient means of improving understanding of the immediate haemodynamic effects of carotid endarterectomy. It is useful in everyday practice to confirm the adequacy of endarterectomy, particularly in the absence of other methods of quality control. Duplex ultrasonography might still be necessary after surgery if the flowmeter does not demonstrate an increase in flow compared with the preoperative value. PMID- 8205428 TI - Postoperative changes in resting energy expenditure and interleukin 6 level in infants. AB - The relationship was determined between resting energy expenditure (REE) and interleukin (IL)6 level following surgery in infants. Sixteen infants of mean(s.e.m.) weight 3.2(0.2) kg undergoing uncomplicated surgery were studied. The operative stress score was recorded and plasma IL-6 levels were measured before and 4, 8, 12 and 24 h after surgery. Respiratory gas exchange was measured by indirect calorimetry before and at 2, 4, 6, 8, 10, 12, 24 and 48 h. Urinary nitrogen excretion was measured and calculated. IL-6 levels increased significantly after surgery (P = 0.006) and were maximal at 12 h. There was a linear correlation between the increase in IL-6 level and operative severity score (r = 0.61, P = 0.012). REE increased significantly after operation (P < 0.001), peaking at 2-4 h, and returned to baseline levels by 12 h. The changes in REE preceded those in IL-6. IL-6 is a marker of the stress response in infants and may play a role in the subsequent modulation of this response. PMID- 8205429 TI - Management of non-palpable breast lesions detected mammographically. AB - A total of 212 consecutive fine-wire localization breast biopsies in 202 patients were performed on impalpable mammographically suspicious lesions. Preoperative fine-needle aspiration cytology was performed on 159 lesions and was valuable in planning the extent of the fine-wire localization biopsy. All 212 target lesions were accurately biopsied during the initial surgery. Overall, 134 lesions were malignant and 78 benign (benign:malignant ratio 1:1.72), with fewer biopsies for benign lesions performed in screened patients (benign:malignant ratio 1:2.43) than in those with symptoms (ratio 1:1). Breast conservation was achieved in 72 patients (80 per cent) with screen-detected in situ or invasive carcinoma and in 19 of 37 presenting via a symptomatic clinic. In 160 of 202 patients (79 per cent) the initial fine-wire localization biopsy was diagnostic and therapeutic. PMID- 8205430 TI - Treatment of pleural effusion of cirrhotic origin by videothoracoscopy. PMID- 8205431 TI - Suction versus siphon drainage after axillary surgery for breast cancer: a prospective randomized trial. PMID- 8205432 TI - Value of Nissen fundoplication in patients with gastro-oesophageal reflux judged by long-term symptom control. AB - A total of 160 patients treated by Nissen fundoplication for uncomplicated gastro oesophageal reflux disease were studied over a 20-year period. Recurrent reflux and side-effects were assessed yearly after surgery. No objective tests for reflux were performed during follow-up if patients were asymptomatic. Perioperative mortality and technique-related morbidity rates were both 2 per cent. At the latest evaluation, 79 per cent of patients were completely relieved of reflux symptoms, 85 per cent had symptoms of Visick grade 1 or 2 and 89 per cent would be willing to undergo surgery again under the same conditions. Actuarial analysis showed that the success rate of fundoplication was 92 per cent at 20 years. Fourteen patients (9 per cent) developed side-effects after fundoplication and had continuing disability. Nissen fundoplication achieves permanent control of reflux symptoms in most patients with few complications and has a high degree of patient satisfaction. PMID- 8205433 TI - Non-radical therapy for early gastric cancer. AB - To assess the potential benefit of R2 gastrectomy for patients with early gastric cancer, complications and long-term survival of patients who underwent conventional resection with limited lymphadenectomy (R1 gastrectomy) were analysed retrospectively. Resection margins of all 46 consecutive patients were free from tumour. Tumours were limited to the mucosa in 35 patients and infiltrated the submucosa in 11. Positive lymph nodes were found in two patients. The 30-day mortality was two patients, and cardiac and pulmonary complications occurred in five and six respectively. Anastomotic leakage developed in two patients. During 5 years of follow-up two patients died from tumour recurrence; one of these had lymph node metastases at the initial resection. Resection with limited lymphadenectomy for early gastric cancer results in a 91 per cent 5-year survival rate without the need for R2 gastrectomy with its probably higher morbidity and mortality. PMID- 8205434 TI - Laparoscopic highly selective vagotomy. AB - Between February 1991 and August 1992, 35 patients underwent laparoscopic highly selective vagotomy (HSV) for recurrent duodenal ulcer disease. An antireflux procedure was also performed in 25 of these patients. There was no 30-day mortality and morbidity. The mean operating time was 110 (range 85-205) min for HSV and 155 (range 100-300) min for vagotomy and antireflux repair. Follow-up is short but initial postoperative gastric acid secretion studies have demonstrated results similar to those obtained after conventional open HSV. The main advantage of laparoscopic HSV is the reduction of 70 per cent in hospital stay and 50 per cent in the overall recovery period compared with open surgery. PMID- 8205435 TI - Effects of minimally invasive surgery on hypochlorous acid production by neutrophils. AB - The production of chlorinated oxidants such as hypochlorous acid is a central antimicrobial and immunoregulatory function of neutrophils. Neutrophil hypochlorous acid production was compared in patients undergoing uncomplicated laparoscopic surgery (group 1) and those submitted to conventional open surgery (group 2). Preoperative peak hypochlorous acid production was similar in the two groups (mean(s.e.m.) 0.60(0.05) versus 0.69(0.06) nmol/min respectively). In group 2, mean(s.e.m.) neutrophil hypochlorous acid production fell significantly on day 1 after surgery (0.36(0.05) nmol/min; P < 0.01) but this did not occur in group 1 (0.63(0.07) nmol/min). By day 6 hypochlorous acid kinetics had returned to preoperative levels in both groups. Minimally invasive surgery is less disruptive of neutrophil function than conventional open procedures. PMID- 8205436 TI - Strictureplasty without concomitant resection for small bowel obstruction in Crohn's disease. AB - The efficacy of strictureplasty in the treatment of Crohn's disease is often attributed in part to concomitant resection of strictured small bowel segments. Fifty-four patients with obstructive Crohn's disease who underwent 215 strictureplasty procedures (Heineke-Mikulicz, 179; Finney, 36) without concomitant resection of small bowel were reviewed. The median age was 38 (range 18-66) years and the median follow-up 3 (range 1-7) years. The mean number of strictureplasties per patient was 4 (range 1-13). Twenty-four patients had undergone at least one previous small bowel resection. There was no operative death. Intra-abdominal abscess and enterocutaneous fistula occurred in two patients each and reoperation for sepsis was needed in one. At 1 year after surgery the median weight gain was 4 kg; all but two patients had relief of obstructive symptoms and 26 of 37 were weaned off steroids. Symptomatic recurrence occurred in 14 patients and seven required reoperation. Rates of recurrent stricture and of new stricture or perforative disease were 2.3 per cent of strictureplasty sites and 26 per cent of patients respectively. PMID- 8205437 TI - Atrial natriuretic peptide and glucagon release in experimental intestinal ischaemia and reperfusion. AB - Intestinal ischaemia and reperfusion cause changes in cardiovascular and pulmonary function. In a rat model, the plasma concentrations of atrial natriuretic peptide (ANP) and pancreatic glucagon rose on reperfusion after 20 min of intestinal ischaemia, coinciding with significant arterial hypotension: mean(s.e.m.) ANP 79(13) versus control 36(4) fmol ml-1 (P < 0.01); and mean(s.e.m.) glucagon 22(2) versus control 10(1) fmol ml-1 (P < 0.001). Glucagon was also released on reperfusion after 5 min of ischaemia: mean(s.e.m.) 18(2) fmol ml-1 (P < 0.001 versus control). In a second experiment, pretreatment of rats with allopurinol did not prevent arterial hypotension but abolished ANP release (mean(s.e.m.) 36(2)fmol ml-1 versus no pretreatment 70(7) fmol ml-1, P < 0.05), while glucagon release was unaffected. The release of ANP, but not that of glucagon, is therefore mediated by oxygen free radicals and may signify cardiac and/or pulmonary injury or dysfunction. The actions of these peptides may be relevant in the pathophysiological perturbation of intestinal ischaemia reperfusion. PMID- 8205438 TI - Evaluation of direct and indirect inguinal hernia by computed tomography. AB - The importance of venous distension of the pampiniform plexus in the prevention of inguinal hernia was evaluated. Functional closure of the inguinal canal was investigated by computed tomography during a Valsalva manoeuvre in a normal individual and 12 men with unilateral inguinal herniation, one of whom had previously undergone herniorrhaphy. Thus, 13 normal canals were evaluated along with five with direct and seven with indirect hernia. In all normal canals a rise in intra-abdominal pressure increased the cross-sectional area of the part of the pampiniform plexus located in the medial end of the canal, thereby filling the empty space and preventing herniation. In the lateral part the plexus was compressed against the external aponeurosis by the fascia transversalis in a valve-like fashion. In cases of direct inguinal herniation the distended pampiniform plexus was displaced by the hernia sac during the Valsalva manoeuvre, but in indirect hernia impaired swelling of the pampiniform plexus was seen. It is suggested that this observation could help to explain the normal mechanism of closure of the inguinal canal. PMID- 8205439 TI - Anterior approach for mesh repair of inguinofemoral hernia after obliteration of the inguinal ligament. PMID- 8205440 TI - Effect of human leucocyte antigen matching on the incidence of acute rejection in renal transplantation. AB - The influence of human leucocyte antigen (HLA) matching on the incidence of acute rejection and graft survival was examined in 181 consecutive patients receiving cadaveric renal transplants. Allografts with better HLA-DR and HLA-B matching showed significantly lower rejection rates than less well matched grafts on both univariate (rejection rates 25, 62 and 82 per cent for zero, one and two DR mismatches; P < 0.001) and multivariate analysis. Rejection episodes occurred earlier in mismatched grafts (P < 0.001). Superior matching was associated with improved graft function at 1 year after transplantation (mean serum creatinine level 137, 180 and 225 mumol l-1 for zero, one and two DR mismatches; P < 0.05). No association was, however, demonstrated between the degree of matching and overall graft survival. Good HLA matching reduces the number of acute rejection episodes, producing significant savings in drug costs and hospital stay. Long term graft function is improved and minimizing early graft damage helps to avoid later development of chronic rejection. PMID- 8205441 TI - Hepatic resection with a long sheathed needle: a simple technique. PMID- 8205442 TI - Bacterial translocation, intestinal ultrastructure and cell membrane permeability early after major liver resection in the rat. AB - The process and route of bacterial translocation from the gut after major liver resection remain unclear. In the present study enteric bacterial translocation, enterocyte ultrastructure in the ileum and colon, the process and route of bacterial invasion and the permeability of the cell membrane system and blood tissue barrier were evaluated in rats receiving sham operation, and 70 or 90 per cent hepatectomy. The incidence of bacterial translocation to mesenteric lymph nodes was 80-100 per cent in rats 6 h after 70 per cent and 2-4 h after 90 per cent hepatectomy, and 80-100 per cent to the systemic circulation 2-4 h after 90 per cent hepatectomy but only 20 per cent to the portal vein. An increase in bacterial adherence to the intestinal surface, damage to the permeability of the cell membrane system and blood-tissue barrier, and pathological alterations in the ileum and colon developed, correlating with the extent of liver removed and the time that had passed after hepatectomy. Most translocating bacteria appeared in morphologically intact enterocytes with increased membrane permeability, in antigen-presenting cells and in submucosal lymphatics, but some bacteria were also seen within damaged enterocytes 4h after 90 per cent hepatectomy. These results indicate that altered permeability of the cell membrane system may be one of the earliest characteristics of challenged enterocytes, and that enteric bacteria translocate through both morphologically normal and abnormal enterocytes. Translocation occurred mainly into the lymphatics, bacteria either being 'carried' by antigen-presenting cells or entering by active invasion. PMID- 8205443 TI - Intraluminal implantation of gallbladder cancer into the bile ducts. PMID- 8205444 TI - Angiographic changes in the hepatic artery after skeletonization resection for biliary tract cancer. AB - Using preoperative and postoperative arteriography, angiographic changes in the hepatic artery were studied after skeletonization of the hepatoduodenal ligament and hepatic resection for biliary tract carcinoma. Of 52 patients evaluated (32 with carcinoma of the bile duct, 20 with gallbladder cancer), no angiographic changes were apparent after operation in 30 (58 per cent) and there were pathological findings in 22 (42 per cent; smooth stenosis in five patients, irregular stenosis in seven, a beaded appearance in four, dilatation in two, obstruction in four). Based on angiographic findings, patients were classified into three subgroups (no change, 30 patients; irregular form, 18; obstructed, four). Postoperative liver function was also evaluated. No definite correlation was evident between angiographic findings and the incidence of hepatic failure or liver dysfunction in the first month after operation. Given that connective tissue and lymph node dissection in the hepatoduodenal ligament is essential for curative resection of biliary tract carcinoma, these findings suggest that skeletonization is an acceptable operative procedure. PMID- 8205445 TI - Combined laparoscopic and endoscopic treatment of gallstones and bile duct stones: a prospective study. AB - In patients with symptomatic gallstones the management of choledocholithiasis has been controversial since the introduction of laparoscopic cholecystectomy. A prospective study was made of 300 consecutive patients with symptomatic gallstones managed by laparoscopic cholecystectomy and preoperative endoscopic retrograde cholangiography (ERC) over 2 years. Fourteen patients were excluded either because urgent surgery was required or because they were unfit for laparoscopic cholecystectomy. ERC was performed on 96 patients (34 per cent) who were at risk of choledocholithiasis. The presence of bile duct calculi was confirmed in 59 patients (21 per cent of the total, 61 per cent of those undergoing ERC); stones were removed endoscopically in 53 cases (90 per cent of attempts). The remaining six patients underwent open cholecystectomy and bile duct exploration. Laparoscopic cholecystectomy was attempted in 280 patients (98 per cent); it was necessary to convert to open operation in only three (1 per cent). There were no deaths, no retained stones and no bile duct injuries, and only three patients (1 per cent) developed a significant postoperative complication. Symptomatic gallstones can be managed by preoperative ERC and laparoscopic cholecystectomy with minimal morbidity and mortality. PMID- 8205446 TI - Prospective randomized study of preoperative bowel cleansing for patients undergoing colorectal surgery. AB - Three different methods of preoperative bowel preparation were tested in a prospective randomized trial examining efficacy and morbidity. In all, 163 patients were treated by gut irrigation with Ringer's lactate, Prepacol or polyethylene glycol (PEG). Fluid retention, cleansing effect, postoperative complications and subjective acceptance were documented. Relevant weight gain and decrease in haematocrit indicating fluid retention were seen only after the use of Ringer's lactate. There were no significant differences in bowel cleansing. In the Prepacol group the postoperative complication rate was significantly increased. Prepacol was tolerated best, with few side-effects. PEG was better tolerated than Ringer's lactate, but vomiting occurred in 2 and 21 per cent of patients respectively. PEG is most suitable for bowel preparation in patients undergoing colorectal surgery. PMID- 8205447 TI - Posterior sagittal anorectoplasty in adults. PMID- 8205448 TI - Abnormal transient internal sphincter relaxation in idiopathic pruritus ani: physiological evidence from ambulatory monitoring. AB - Patients with idiopathic pruritus ani have an abnormal rectoanal inhibitory reflex and a lower threshold for internal sphincter relaxation during the saline continence test. This led to the hypothesis that these patients may exhibit abnormalities of the transient internal anal sphincter relaxation reflex. To study this, 23 men of median age 41 (range 27-64) years with idiopathic pruritus ani and 16 male controls of median age 39 (range 26-68) years were assessed using computerized ambulatory anorectal electromyography and manometry. Resting anal pressure, maximum anal squeeze pressure, internal sphincter electromyogram frequency, the number of internal sphincter relaxations and pudendal nerve terminal motor latency were similar for the two groups. The rise in rectal pressure during internal sphincter relaxation was higher in patients with pruritus than in controls (median (range) 29 (18-60) versus 18 (11-37) cmH2O, P < 0.01). Furthermore, the fall in anal pressure was greater in patients with pruritus than in controls (median (range) 39 (15-52) versus 29 (21-43) cmH2O, P < 0.01). The duration of internal sphincter relaxation was prolonged in patients compared with controls (median (range) 29 (18-55) versus 8 (5-12) s, P < 0.001). Fourteen patients reported staining of underclothes and 17 complained of perianal itch within 1 h of these episodes of abnormal internal sphincter relaxation. Pruritus ani may result from occult faecal leakage as a result of abnormal transient internal sphincter relaxation. PMID- 8205449 TI - The Vascular Surgical Society of Great Britain and Ireland, 27th annual meeting. Manchester, United Kingdom, 18-19 November 1993. Abstracts. PMID- 8205450 TI - Continuous single-layer serosubmucosal anastomosis in the upper gastrointestinal tract and one-layer continuously sutured colonic anastomosis. PMID- 8205451 TI - Subumbilical hernia following laparoscopic cholecystectomy. PMID- 8205452 TI - Raised serum CA125 level in leiomyoma and leiomyosarcoma of gastrointestinal origin. PMID- 8205453 TI - Prognostic significance of histological type in gastric carcinoma with invasion confined to the stomach wall. PMID- 8205454 TI - 'Damage control' in trauma surgery. PMID- 8205455 TI - Laparoscopic treatment of a liver hydatid cyst. PMID- 8205456 TI - Growth areas in hypertension. AB - Essential hypertension is an arbitrarily defined disorder to which both environmental and genetic factors contribute. Identifying these factors is a difficult task because individually their contribution is relatively small and apparent causality may be the result of secondary changes or genetic drift. Associations between elevated blood pressure and genetic or phenotypic characteristics are insufficient therefore to demonstrate a cause and effect relationship. This conclusion requires that stringent criteria are met including the presence of the abnormality at or before the first manifestation of hypertension, co-segregation of the relevant gene, reversibility of hypertension when the abnormality is removed (at least during the early phases of hypertension) and failure of the abnormality to resolve with the correction of hypertension. It is proposed that these conditions constitute 'Koch's postulates' for defining the causes of elevated blood pressure. PMID- 8205457 TI - Environmental factors in the development of essential hypertension. AB - Hypertension is predominantly a disorder of populations in which the fundamental problem is the tendency for blood pressure to rise with age. This phenomenon, which varies markedly across populations, is determined largely by environmental factors. We argue that the most important factors in the development of hypertension at the population level are calorie excess (as manifest by obesity), high salt intake, low potassium intake, physical inactivity, heavy alcohol consumption and psychosocial stress. Potential interactions between these factors (and the genetic endowment) are emphasized. We consider data from studies of blood pressure in children and adolescents and from intervention studies. The hypothesis that essential hypertension is initiated in fetal life is reviewed briefly. It is clear that the current high risk approach to prevention should be supplemented by a population based approach. There is controversy however regarding the value of certain interventions, such as salt restriction, at the population level. Ultimately community intervention trials will be required to resolve these issues. PMID- 8205458 TI - Molecular genetics of susceptibility to the development of hypertension. AB - Blood pressure is a quantitative multifactorial trait with both environmental and genetic determinants, with essential hypertension simply representing one extreme of the blood pressure distribution. While much is known about environmental factors that predispose to the development of hypertension, the nature of the genetic factors that increase such susceptibility remain virtually unknown. However, with advances in molecular techniques, several loci that influence blood pressure in rodents have been identified and recently in two selected sets of human hypertensives, a molecular variant at the angiotensinogen locus has been linked to the tendency to hypertension. It is likely that in the next few years several genetic determinants of blood pressure variability in humans will be identified. Such information will not only increase our understanding of the pathophysiology of hypertension and identify novel treatments but may permit preventative and therapeutic measures to be targetted more specifically than at present. PMID- 8205459 TI - Blood pressure, antihypertensive drug treatment and the risks of stroke and of coronary heart disease. AB - Most evidence about the effects of blood pressure on the risks of cardiovascular disease derives from two principal sources: prospective non-randomised observational studies of the associations between blood pressure and the incidence of stroke and of coronary heart disease, and randomised trials of antihypertensive drug therapy. The focus of the first part of this chapter concerns the evidence from observational studies, which--despite the possibility of confounding by other risk factors--may be more relevant to the eventual effects of prolonged blood pressure differences on stroke and coronary heart disease risk. The focus of the second part concerns the evidence from randomised trials of antihypertensive drug treatment, which are more relevant to assessing how rapidly, and to what extent, the epidemiologically expected reductions in stroke or in coronary heart disease are produced by suddenly lowering blood pressure in middle and old age. PMID- 8205460 TI - Hypertension and the heart. AB - The heart is of great importance in systemic hypertension; it has a role in its pathogenesis but also suffers its consequences. Heart disease is, therefore, often found in hypertensive patients. Patients with hypertension may develop left ventricular hypertrophy, cardiac failure and atherosclerotic vascular problems, such as coronary artery disease, as well as strokes and peripheral vascular disease. There have been a great many advances in our understanding of the pathogenesis of hypertensive heart disease as well as its epidemiology over the last decade and these are reviewed briefly here. PMID- 8205461 TI - Hypertension and the kidney. AB - Hypertension and the kidney are closely linked in several ways. The kidney normally responds rapidly to changes in blood pressure by alteration of renal haemodynamics and sodium excretion. These functions of the kidney are reset in established hypertension. However, several subtle abnormalities of renal function are demonstrable in normotensive offspring of hypertensive parents, suggesting that the kidney may play a central role in the pathogenesis of essential hypertension--a possibility supported by a number of cross-transplantation studies in different animal models of hypertension. Hypertension itself commonly causes severe renal failure when the malignant phase develops, but the question of whether benign hypertension causes renal impairment remains controversial. Firm data that this is so are in general lacking, although in black subjects hypertensive nephropathy appears to be up to 18-fold more frequent than in whites, and is reported as a common cause of end-stage renal failure. The reasons for this racial difference in susceptibility to hypertensive renal injury remain unknown. Secondary hypertension also commonly develops in patients with underlying renal disease, and the co-existence of hypertension with renal impairment greatly worsens the rate of the deterioration of renal function. Effective treatment of hypertension in renal disease, particularly with converting enzyme inhibitors, is capable of slowing the rate of loss of function, both in animal models and in human disease, though in the latter case this benefit has so far been demonstrated unequivocally only in patients with diabetic nephropathy. PMID- 8205462 TI - New mechanisms for corticosteroid-induced hypertension. AB - A substantial proportion of patients with secondary hypertension have disorders of the adrenal cortex. Not surprisingly, corticosteroids were amongst the first putative pathogenic mediators to be investigated in essential hypertension. Despite this long history, there remains controversy about the mechanisms which promote abnormal adrenocortical secretion, the tissues and receptors which mediate corticosteroids' effects on blood pressure, and the relevance of corticosteroids in essential hypertension. Several recent advances relate to adrenocortical secretion in hypertension, but arguably the most significant progress has been in understanding factors which control tissue sensitivity to corticosteroids. It is from this latter perspective that it now seems most likely that the role, if any, of the adrenal cortex in essential hypertension will become apparent. PMID- 8205463 TI - Hypertension and blood vessels. AB - The arterial wall undergoes many changes in hypertension. These changes affect the endothelium, vascular smooth muscle cells and the extracellular matrix of the blood vessel. Current evidence regarding both functional and structural aspects of these changes in the blood vessel wall is reviewed in this article. PMID- 8205464 TI - Hypertension and the brain. AB - The brain plays an important role in the short-term regulation of blood pressure via sympathetic and parasympathetic mechanisms as well as other neurohumoral pathways including the hypothalamo-pituitary axis. The role of the central nervous system in long-term blood pressure control is less well defined but centrally mediated increased sympathetic activity has been identified in the spontaneously hypertensive rat. In addition to the role of the brain in the control of blood pressure and mechanisms of hypertension, there are important effects of blood pressure on brain function. Hypertension is a major risk factor for cerebrovascular disease and stroke. Effective antihypertensive treatment can reduce the relative risk of stroke by up to 40% and control of blood pressure appears to prevent both atherothrombotic and haemorrhagic stroke. PMID- 8205465 TI - Diabetes and hypertension. AB - Hypertension is about twice as common in diabetics as in non-diabetics. The increased prevalence may relate to insulin resistance and its sequelae. Hypertension is a major risk factor for both large and small vessel disease, contributing to accelerated atherogenesis and progression of diabetic nephropathy and retinopathy. Treating raised blood pressure in diabetics is beneficial in the context of large vessel disease and in slowing progression of overt nephropathy. There is controversy as to whether antihypertensives, and particularly ACE inhibitor drugs, will prevent progression from incipient to overt nephropathy. All the major classes of antihypertensives can be used in diabetics, but the thiazide diuretics and beta-blockers have metabolic side-effects which make them less appropriate as first line agents. The calcium antagonists and ACE inhibitors have better metabolic profiles and the latter reduce insulin resistance. ACE inhibitors may also have a renal protective effect in incipient nephropathy although the studies have been fairly short-term and with small patient numbers. Although ACE inhibitors and calcium antagonists are suitable as first line antihypertensives in diabetics, evidence is still lacking that these drugs reduce morbidity and mortality over and above that seen with other antihypertensives. PMID- 8205466 TI - Hypertension and the elderly. AB - Cardiovascular disease remains the major cause of death in elderly people, with hypertension the main treatable risk factor. Despite this there has been little consensus with regard to assessment or treatment of the elderly hypertensive patient. Several recent large intervention trials have shown blood pressure (BP) reduction in elderly patients with combined and isolated systolic hypertension using thiazide diuretics or beta-blockers significantly reduces cardiovascular morbidity and mortality. However, only the STOP-Hypertension Trial has shown a reduction in total mortality with active treatment. Patients under 80 years with an SBP > or = 160 mmHg and DBP > or = 90 mmHg or SBP > or = 160 mmHg and DBP < 90 mmHg should be considered for anti-hypertensive therapy, initially using non pharmacological methods. Thiazide diuretics and beta-blockers remain first-line pharmacological therapy, the long-term benefits of other types of anti hypertensive agent have yet to be assessed. In general the negative attitudes to treating hypertension in the elderly can no longer be upheld, although in certain sub-groups the benefits of treatment are as yet unproven. PMID- 8205467 TI - Measurement of blood pressure in the technological age. AB - Problems with conventional blood pressure measurement using the mercury sphygmomanometer, related to both equipment and technique, are discussed. The effect of observer bias on the measuring procedure is also considered. Blood pressure variability and the phenomenon of 'white coat' hypertension are then described and their impact on the interpretation of hypertensive cardiovascular risk is emphasized. The potential role of electronic sphygmomanometers, and the use of ambulatory BP monitoring equipment, to overcome some of these problems is analysed. Technical factors both in use and interpretation of ambulatory BP data are considered, emphasizing the lack of prospective data and the difficulties in defining a 'normal' range. The current role of such equipment in both research and clinical practice is defined. PMID- 8205468 TI - Hypertension: investigation, assessment and diagnosis. AB - Patients with mild to moderate hypertension require only a simple schedule of investigations, especially if there is a history of stroke or hypertension in first degree relatives. Tests are necessary to profile other cardiovascular risk factors and to detect target organ damage with only limited screening for secondary hypertension. Careful history, physical examination, repeated blood pressure measurements over months and measurements of body mass index, random cholesterol, routine blood chemistry and urinalysis using impregnated paper strips are all that are required. More detailed investigations can be reserved for special groups such as those with peripheral vascular disease or abnormal renal function before or after treatment with angiotensin converting enzyme inhibitors or significant proteinuria or hypokalaemia. Patients with essential hypertension who are smokers with lipid abnormalities may go on to develop superimposed renovascular disease. Severe hypertension at any age and especially if there is a reliable negative family history also merits special consideration. Resistance to antihypertensive treatment is more often due to non-compliance or non-steroidal anti-inflammatory drug use or alcohol abuse than to underlying secondary causes. PMID- 8205469 TI - Management targets and thresholds for treatment. AB - The objectives in managing the hypertensive patient are to reduce or reverse the risks of cardiovascular morbidity and mortality, that are known to be associated with higher levels of arterial pressure. Given the overwhelming evidence from the intervention trials (discussed previously) that the lowering of blood pressure by drugs is associated with a reduction in the incidence of stroke and coronary heart disease events, such objectives are realistic. PMID- 8205470 TI - Non-pharmacological therapy of hypertension. AB - Weight reduction, moderate sodium restriction and alcohol reduction all lower blood pressure significantly in the short-term, and appear feasible in the long term. Dynamic exercise may have a useful role in selected patients. Cessation of cigarette smoking has no important effect on blood pressure itself but is likely to improve the prognosis. No other non-pharmacological intervention warrants a place in routine management on present evidence. Regimens involving combined reduction in weight, salt and alcohol have proved less effective than drug therapy in terms of blood pressure reduction. Hypertensive patients may be shifted from just above some arbitrary intervention level to just below it by non pharmacological treatment, and the perceived benefits of non-pharmacological management may be offset by an increased risk of vascular complications related to suboptimal blood pressure control. Moreover even simple measures such as moderate sodium restriction may affect some aspects of quality of life adversely. Non-pharmacological measures should generally be regarded as useful adjuncts to antihypertensive drug therapy rather than alternatives to it. PMID- 8205471 TI - Cytochemical polarity in lateral geniculate interneurons. AB - To determine the cytochemical composition of presynaptic dendrites, we have examined the distribution of synapsin 1, calcium and calmodulin-dependent protein kinase II (CaM-II), microtubule-associated protein 2 (MAP-2) and spectrin in cat lateral geniculate (LGN) class III cells by immune-EM. Special attention was paid to the dendrites of these interneurons because they are both pre- and postsynaptic. The dendritic proteins MAP-2 and RBC spectrin were not observed in interneuron dendrites but these proteins were localized in relay cell dendrites. The synaptic vesicle-associated protein synapsin 1 was present in all synaptic vesicle containing profiles, including dendritic terminals. CaM-II, the major postsynaptic density protein, was found in all dendrites. Thus, the LGN interneuron dendritic compartment displays both axonal and dendritic cytochemical properties. The results suggest the possibility of unique molecular interactions in interneuron dendritic terminals. PMID- 8205472 TI - Distribution of GABAA and GABAB binding sites in the cochlear nucleus of the guinea pig. AB - We compared the distribution of GABAA and GABAB binding sites in the cochlear nucleus using quantitative receptor autoradiography with [3H]GABA. To visualize GABAA binding sites, GABAB binding sites were blocked with +/- baclofen. To visualize GABAB binding sites, isoguvacine was used to block GABAA binding sites. GABAA binding sites predominated over GABAB, although there were marked regional differences in the distribution of binding. In the ventral cochlear nucleus, GABAA and GABAB binding sites were concentrated in the peripheral granule cell cap, with low binding levels in the central region. In the dorsal cochlear nucleus, binding was concentrated in the superficial (fusiform and molecular) layers, with a distinct laminar pattern. GABAA binding sites predominated in the fusiform cell layer. The molecular layer contained the highest level of GABAB binding sites in the entire cochlear nucleus. These results suggest that GABAergic inhibition in the cochlear nucleus is mediated both by GABAA and GABAB receptors, particularly in the dorsal cochlear nucleus. However, low levels of binding in areas such as the magnocellular regions of the ventral cochlear nucleus, known to contain abundant GABAergic synapses, suggest heterogeneity of GABA receptors in this auditory nucleus. PMID- 8205473 TI - Progesterone 5-alpha-reduction in neuronal and in different types of glial cell cultures: type 1 and 2 astrocytes and oligodendrocytes. AB - Progesterone, like testosterone, can be converted in the brain into 5-alpha reduced metabolites (5-alpha-pregnan-3,20-dione, DHP; 5-alpha-pregnan-3-alpha-ol 20-one, THP). Recently we have shown that testosterone is 5-alpha-reduced to DHT mainly in neurons, while glial cells possess this enzymatic activity only in limited amounts. On the other hand, a glial cell type (type 1 astrocytes) is almost exclusively responsible for the further metabolism of DHT into 3-alpha diol. The aim of the present studies was that of evaluating the formation of the 5-alpha-reduced metabolites of progesterone in cultures of neurons, type 1 and 2 astrocytes and oligodendrocytes. The data here presented indicate that, similarly to what happens when testosterone is used as the substrate, the 5-alpha-reductase which metabolizes progesterone shows a significantly higher activity in neurons than in glial cells; however, also type-1 and type-2 astrocytes as well as oligodendrocytes possess some ability to 5-alpha-reduce progesterone. On the contrary, the 3-alpha-hydroxysteroid dehydrogenase (3-alpha-HSD), the enzyme which converts DHP into THP, appears to be mainly present in type-1 astrocytes; much lower levels of this enzyme are present in neurons and in type-2 astrocytes. At variance with the previous results obtained utilizing androgens as precursors, oligodendrocytes show a considerable 3-alpha-HSD activity, even if this is statistically lower than that present in type-1 astrocytes. The existence of isoforms of the enzymes involved in androgen and progesterone metabolism may explain these data. PMID- 8205474 TI - AMPA-selective glutamate receptor subtype immunoreactivity in the entorhinal cortex of non-demented elderly and patients with Alzheimer's disease. AB - The present work employed immunocytochemical techniques and examined the distribution and cytological features of the AMPA receptor subunits, GluR2/3 and GluR1 within the entorhinal cortex of non-demented elderly (NC), patients with neuropathological and clinical verification of Alzheimer's disease (AD) and patients without a clinical history of dementia yet exhibiting sufficient quantities of senile plaques to meet neuropathological criteria of Alzheimer's disease (HPND). In NC cases, GluR2/3-immunolabeled neurons were abundantly distributed throughout layers II, III, V and VI of the entorhinal cortex. In contrast, GluR1-positive cells were comparatively sparse in number and largely restricted to layers V and VI. In AD, GluR2/3- and GluR1-labeled neurons were markedly reduced. Similarly, adjacent Nissl-stained tissue sections revealed substantial cell loss in the entorhinal cortex thus providing a reasonable explanation for the loss of these receptor subunits. Importantly, a dramatic loss of GluR2/3- and GluR1-immunolabeled neurons is also observed in the HPND cases, although examination of Nissl-stained tissue sections reveals little if any evidence of cell loss. The latter data suggest that a 'down-regulation' of these receptor subunits occurs prior to the actual loss of these cells. Furthermore, we hypothesize that the decrease of specific AMPA receptor subunits may influence neuronal vulnerability via a mechanism involving increased intracellular calcium and the destabilization of intracellular calcium homeostasis. PMID- 8205475 TI - The control of circadian rhythms and the levels of vasoactive intestinal peptide mRNA in the suprachiasmatic nucleus are altered in spontaneously hypertensive rats. AB - Vasoactive intestinal peptide (VIP) has been localized within the suprachiasmatic nucleus of the hypothalamus (SCN) and appears to play an important role in the entrainment of circadian rhythms with the light-dark (LD) cycle. The spontaneously hypertensive rat (SHR), an inbred strain used extensively in research on primary hypertension, has significantly more VIP mRNA in its brain than normotensive Wistar-Kyoto control (WKY) rats. Because VIP levels are abnormally high in SHR rats the present study examined whether the mechanisms controlling circadian rhythms are also altered in SHR rats. When entrained to a 24 h LD cycle, SHR rats began their wheel-running rhythm approximately 1.5 h earlier than WKY controls. SHR rats re-entrained to a phase delay in the LD cycle more slowly than did WKY rats, but tended to re-entrain to a phase advance more rapidly. The free-running period of SHR rats in both constant light and constant dark was significantly shorter than that of WKY rats. In SHR rats, phase delays produced by 1-h pulses of light were less than one-half the magnitude of the delays seen in WKY rats; however, the phase advances were nearly twice that of WKY rats. Using in situ hybridization, the SCN levels of mRNA encoding VIP were found to be significantly greater in SHR rats, but the mRNA levels of another peptide important for entrainment, gastrin releasing peptide, did not differ between SHR and WKY rats. These data indicate that the mechanisms controlling circadian rhythms in SHR rats differ significantly from those controlling rhythms in WKY rats and that VIP mRNA is significantly elevated within the SCN of SHR rats. The role of VIP in the entrainment of circadian rhythms is discussed. PMID- 8205476 TI - Increased occupation of D1 and D2 dopamine receptors accompanies cocaine-induced behavioral sensitization. AB - In rats exhibiting behavioural sensitization after daily cocaine (10 mg/kg, i.p.) injections, the occupation of D1 and D2 dopamine receptors by dopamine, measured as protection from N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) receptor denaturation, was increased by about 100% compared to animals receiving cocaine in a treatment regimen that produced behavioural tolerance. Co-administration with nimodipine, an agent that blocks the impulse-dependent increase in synaptic concentrations of dopamine caused by cocaine, not only blocked sensitization but also blocked the increase in occupation of receptors. These findings strongly support the hypothesis that enhanced dopamine release and subsequent interaction with dopamine receptors is a substrate for behavioural sensitization to cocaine and have implications for the pharmacotherapy of cocaine abuse. PMID- 8205477 TI - Immunocytochemical detection of oxytocin in the supraependymal neuronal complex of the golden hamster. AB - A system of intraventricular neuronal perikarya and processes known as the supraependymal neuronal complex (SENC) is located on the floor of the third ventricle and innervates the neurohypophysis of the golden hamster (Mesocricetus auratus). Immunocytochemical techniques were used to determine if oxytocin and/or vasopressin are present in the neuronal elements of the SENC. Oxytocinergic fibers were observed to breach the ependyma of the median eminence and enter the neuropil of the SENC. Some of these fibers traverse the SENC to reach the adjacent ependymal surface and terminate on the floor of the third ventricle while others terminate within the neuropil of the SENC. These oxytocinergic fibers may be involved in the secretion of oxytocin into the cerebrospinal fluid (CSF). Vasopressinergic fibers were detected in the neuropil of the SENC in only one of four specimens examined and are assumed to be aberrant processes from the hypothalamo-neurohypophysial tract. Neither oxytocin nor vasopressin were detected in the neurons intrinsic to the SENC. The function of the SENC is unknown, but it may be involved in regulatory processes in which CSF oxytocin has been implicated, such as osmotic homeostasis and/or cardiovascular reflexes. PMID- 8205478 TI - Solubilization and purification of a high affinity neurotensin receptor from newborn human brain. AB - High affinity neurotensin receptors were solubilized in an active form from newborn human brain using the non-denaturing detergent 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS). The solubilized receptor was purified in a single step by affinity chromatography. The binding properties of the purified receptor towards [125I-Tyr3]neurotensin are very similar to those of the membrane bound and of the crude CHAPS-solubilized receptor in terms of affinity and specificity. The purified receptor is a single protein chain of molecular weight 100 kDa as shown by gel filtration and by affinity labelling with [125I-Tyr3]neurotensin in the presence of the cross linking agent disuccinimidyl suberate. PMID- 8205479 TI - The role of multiple opioid receptors in the potentiation of reward by food restriction. AB - Chronic food restriction and weight loss were previously shown to produce a naltrexone-reversible facilitation of perifornical lateral hypothalamic self stimulation. In the present study, high affinity receptor-selective antagonists were used to determine the particular opioid receptor type(s) that mediates the facilitation of reward by food restriction. Separate groups of food-restricted and ad libitum fed rats were used to conduct i.c.v. dose-response studies with TCTAP (mu), norbinaltorphimine (kappa), and naltrindole (delta). The highest dose of naltrindole (50.0 nmol) raised self-stimulation threshold independently of feeding condition. This suggests that delta opioid activity is involved in self stimulation under basal conditions and may explain previous findings that high systemic doses of naloxone or naltrexone reduce self-stimulation. The highest doses of TCTAP and norbinaltorphimine (5.0 and 50.0 nmol, respectively) reversed the lowering of self-stimulation threshold produced by food restriction while having no effect on thresholds of ad libitum fed rats. These results suggest that state-dependent mu and kappa opioid activity facilitate reward. Since food restriction is known to increase the rewarding effect of food and drugs of abuse, the opioid mechanism identified in the present study may mediate adaptive behavior and, under some circumstances, pathological behavior. The possible relation of state-dependent opioid activity to Anorexia Nervosa, binge eating, and the high comorbidity of eating disorders and substance abuse is discussed. PMID- 8205480 TI - The nigrostriatal dopamine system: role in the development of hypertension in spontaneously hypertensive rats. AB - The effects of lesions in the pars compacta of the substantia nigra of 4-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were studied on (a) changes in blood pressure during a period of 6 weeks following lesioning, and (b) dopamine and metabolite concentrations in the caudate nucleus and (c) the in vitro release of [3H]dopamine from caudate nucleus slices 6 weeks after the lesioning. We report here that substantia nigra lesions caused a profound attenuation of the development of hypertension in SHR. No effect on heart rate was observed. Whereas the concentrations of dopamine and 3,4 dihydroxyphenylacetic acid (DOPAC) in the caudate nucleus were not different, the amount of homovanillic acid (HVA) and the ratios DOPAC/dopamine and HVA/dopamine were lower in sham-treated SHR than in sham-treated WKY, indicating a lower turnover of dopamine in SHR. Six weeks after lesioning, the concentrations of dopamine, DOPAC and HVA were decreased in the caudate nucleus (46-66%) of both strains, whereas DOPAC/dopamine and HVA/dopamine ratios tended to be increased in both SHR and WKY. Using an in vitro superfusion method, it was found, that the electrically stimulated release of [3H]dopamine from caudate nucleus slices of sham-treated SHR was lower than from slices of sham-treated WKY at the age of 10 weeks. Six weeks after lesioning, the stimulus-evoked release of [3H]dopamine from the remaining terminals was significantly increased in caudate nucleus slices of SHR, whereas the difference did not reach statistical significance in WKY.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205481 TI - Age-related phospholipid hydroperoxide levels in gerbil brain measured by HPLC chemiluminescence and their relation to hydroxyl radical stress. AB - Phosphatidylcholine hydroperoxide (PCOOH) was directly quantified in the hippocampus, cortex and striatum from young (3 months), middle-aged (15 months) and old (20 to 24 months) gerbils by an HPLC-chemiluminescence assay. PCOOH levels in hippocampus and cortex were found between 8.05 to 8.58 pmol/mg tissue and no statistically significant difference was found across the age groups. In striatum, however, PCOOH levels were significantly higher in middle-aged and old gerbils compared to those in young animals. The regional comparison showed that PCOOH levels were significantly higher in striatum than in cortex or hippocampus for all the age groups. Moreover, this regional difference increased with aging, from approximately 20% in young animals to 30% and 40% in middle-aged and old gerbil striatum. PCOOH to phospholipid ratio is approximately the same for all age groups at the level of 1.5/10,000, although it is slightly lower in the cortex. The hydroxyl radical levels in the brain were also measured by the formation of its salicylate trapped product 2,3-DHBA and used as a measure of oxidative stress. The PCOOH levels was used as a measure of oxygen radical induced lipid peroxidative damage. PCOOH as a function of hydroxyl radical stress was calculated and expressed as PCOOH/2,3-DHBA, representing the oxidative damage as a function of the level of oxidative stress. It also implies the tissue susceptibility to oxidative stress and the efficiency of the antioxidant systems. In hippocampus and cortex, the ratios are high in young gerbils, decrease at middle-age and significantly increase in the old.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205482 TI - Neurocircuitry of illness-induced hyperalgesia. AB - We have previously demonstrated that illness-inducing agents such as lithium chloride (LiCl) and the bacterial cell wall endotoxin lipopolysaccharide (LPS) produce hyperalgesia on diverse pain measures. The present series of studies attempted to identify the neurocircuitry mediating these effects. These studies have demonstrated that illness-inducing agents produce hyperalgesia by activating: (a) peripheral nerves rather than by generating a blood-borne mediator (Expt. 1); (b) vagal afferents, specifically afferents within the hepatic branch of the vagus (Expt. 2); (c) as yet unidentified brain site(s) rostral to the mid-mesencephalon (Expt. 6); (d) a centrifugal pathway that arises from the nucleus raphe magnus, and not from the adjacent nucleus reticularis paragigantocellularis pars alpha (Expts. 4 and 5); (e) a centrifugal pathway in the dorsolateral funiculus of the spinal cord (Expt. 3); and (f) the same centrifugal pathways for diverse illness inducing agents (Expts. 3, 7 and 8). These data call for the re-evaluation of a number of assumptions inherent in previous studies of hyperalgesia. PMID- 8205483 TI - Sympathetic denervation and the cerebrovascular response to hypertension induced by NG-nitro-L-arginine methyl ester. AB - Cerebral blood flow and glucose utilization were measured in rat neocortex, using [14C]iodoantipyrine and 2-deoxy-D-[14C]glucose quantitative autoradiography, respectively, following nitric oxide synthesis inhibition with L-NAME. In intact animals cortical blood flow was decreased, despite increased arterial blood pressure above autoregulatory limits, whilst glucose use remained unaffected. Unilateral sympathectomy at the superior cervical ganglion had no effect, suggesting that the autoregulatory response to L-NAME-induced hypertension is independent of sympathetic activity. PMID- 8205484 TI - Population synaptic potentials evoked in lumbar motoneurons following stimulation of the nucleus reticularis gigantocellularis during carbachol-induced atonia. AB - The effect of electrical stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) on lumbar spinal cord motoneurons was studied in the decerebrate cat using sucrose-gap recordings from ventral roots. The NRGc was stimulated ipsi- and contralaterally before and during atonia elicited by the microinjection of carbachol into the pontine reticular formation. Prior to carbachol administration, the NRGc-induced response recorded from the sucrose-gap consisted of two consecutive excitatory population synaptic potentials followed by a long-lasting, small amplitude inhibitory population synaptic potential. Following carbachol injection, the same NRGc stimulus evoked a distinct, large amplitude inhibitory population synaptic potential, whereas the excitatory population synaptic potentials decreased in amplitude. In addition, after carbachol administration, the amplitude of the monosynaptic excitatory population synaptic potential, which was evoked by stimulation of group Ia afferents in hindlimb nerves, was reduced by 18 to 43%. When evoked at the peak of the NRGc induced inhibitory response, this potential was further decreased in amplitude. Systemic strychnine administration (0.07-0.1 mg/kg, i.v.) blocked the NRGc induced inhibitory population synaptic potential and promoted an increase in the amplitude of the excitatory population synaptic potentials induced by stimulation of the NRGc and group Ia afferents. These data indicate that during the state of carbachol-induced atonia, the NRGc effects on ipsi- and contralateral spinal cord motoneurons are predominantly inhibitory and that glycine is likely to be involved in this inhibitory process. These results support the hypothesis that the nucleus reticularis gigantocellularis is part of the system responsible for state-dependent somatomotor inhibition that occurs during active sleep. PMID- 8205485 TI - QX-314 blocks the potassium but not the sodium-dependent component of the opiate response in locus coeruleus neurons. AB - Opiates hyperpolarize locus coeruleus neurons by simultaneously opening K+ channels and turning off a resting Na(+)-dependent inward current. Intracellularly applied QX-314 reduced the opiate current to approximately 40% of the control and the residual current did not reverse near EK, suggesting lack of a significant K+ component. Replacement of Na+ virtually abolished the residual opiate response. Thus, QX-314 blocks the K+ but not the Na(+)-dependent component of the opiate-induced outward current in LC neurons. PMID- 8205486 TI - Responses of neurons in the ventrolateral orbital cortex to noxious cutaneous stimulation in a rat model of peripheral mononeuropathy. AB - The responses of ventrolateral orbital cortex neurons to noxious cold pressor were compared in rats with loose ligatures tied around their sciatic nerve with those in rats in which the sciatic nerve was exposed but not ligated. In ligated rats more cells responded to cold pressor and their average afterdischarges were longer. There were no differences in the background firing rate or the magnitude of response to the cold pressor between the two groups. PMID- 8205487 TI - Specific expression of type II protein kinase c after axotomy in the dorsal motor nucleus of the vagus nerve and the hypoglossal nucleus. AB - Protein kinase C (PKC) and growth-associated protein-43 (GAP-43) were investigated immunohistochemically in the dorsal motor nucleus of the vagus nerve and the hypoglossal nucleus after axotomy using monoclonal antibodies against type I, II and III PKC and GAP-43. In the control side of both nuclei, anti-type I and II PKC weakly stained neuronal cell bodies, while anti-type III PKC did not show any reaction with neurons. In the axotomized side of both nuclei, anti-type II PKC antibody intensely stained affected nerve cell bodies as well as plasma membrane. Some of the severed neurons showed intensified reactions for both anti type II PKC and anti-GAP-43 antibodies in the serial sections. These findings suggest that axotomy increases the type II PKC of the severed neurons, and type II PKC seems to phosphorylate some protein, such as GAP-43, and plays some role in the retrograde neuronal reaction. PMID- 8205488 TI - Post-hatching inhibition of aromatase activity does not alter sexual differentiation of the zebra finch song system. AB - Hatchling zebra finches were treated with fadrozole, an aromatase (estrogen synthesis) inhibitor, to test whether estrogen is required for normal masculine development of the song system. Injections on posthatching days 1-30 had no effect on the volumes of the robust nucleus of the archistriatum (RA) and area X or on neuron soma size in RA and high vocal center (HVC) measured on day 31. These results argue against the importance of estrogen in masculinization of the song system in males after hatching. PMID- 8205489 TI - Motor learning in lurcher mutant mice. AB - Lurcher mutant mice, characterized by degeneration of the olivo-cerebellar system, were evaluated in two tests of motor coordination: the inclined screen test and the tilted platform test. Lurcher mutants were not impaired, in comparison to normal littermate controls, in the inclined screen test. In the tilted platform test, lurcher mutants fell more quickly than normal mice. However, with repeated testing, the amount of time spent on the platform by lurcher mutants and controls increased at the same rate within a 3 day period. These results demonstrate that lurcher mutants, although ataxic, have spared motor capabilities. In a test where motor deficits occurred, rapid improvement was seen. Thus, in spite of massive cerebellar degeneration, there was no evidence of a decreased rate in motor learning. PMID- 8205490 TI - Cortical regulation of acetylcholine release in rat striatum. AB - The effect of electrical stimulation of the prefrontal cortex (PFC) on acetylcholine (ACh) release in the dorsal striatum was investigated using on line in vivo microdialysis. ACh output was sampled before, during and after 20-min periods of 50 and 100 microA stimulation in awake, unrestrained rats. Both currents increased extracellular ACh by approximately 30% above baseline. ACh concentrations reached their maximum values during the last 10 min of the stimulation period and returned to baseline within 20 min. These results provide direct functional evidence for cortical modulation of cholinergic interneurons in the striatum. PMID- 8205491 TI - Reconstruction of pressure and flow waves in the artery. AB - Cardiac arrests were induced in 22 rabbits by applying electrical stimulations to the vagus nerve while electrocardiogram (ECG), and blood pressure (BP) and blood flow (BF) either from the carotid artery or from the femoral artery were monitored continuously. Under the assumption that the arterial system is a linear and time-in-variant (LTI) system, the "single-pulse-response" (SPR), i.e. the response to a single ventricular contraction of BP (Pm0) and BF (Qm0) were calculated by subtracting the wave from itself after being shifted backward by one R-R interval. Pm0 and Qm0 were then used to construct the original waves by summing successive SPR's at a repetitive period of one R-R interval. The result showed that both pressure and flow waves in the carotid artery and in the femoral artery could be successfully reconstructed from the corresponding SPR's. The result was compared to the voltage across the capacitor in the two-element windkessel model when a train of impulses were given, beginning from the zero state. We concluded (1) the arterial system, being a physical system, can be treated as an engineering system, and (2) the observed BP and BF in the artery can be regarded as the summation of arterial responses to repetitive pulses generated by the left ventricle and be analyzed accordingly. PMID- 8205492 TI - Magnetic resonance imaging of the kidneys in paroxysmal nocturnal hemoglobinuria. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is a blood cell disorder characterized by repeated intravascular hemolysis. Histologically, there is hemosiderin deposition in the proximal tubular cells of the renal cortex. We report a case of PNH with characteristic magnetic resonance findings. The signal intensity of the renal cortex was markedly decreased in various pulse sequences because of the T2 shortening paramagnetic effect of hemosiderin. The significance of signal intensity ratios between renal cortex and medulla, renal cortex and skeletal muscle are discussed. These ratios of the PNH patient are significantly different from those of normal controls (p = 0.0000). PMID- 8205493 TI - Characteristics of carotid pressure and flow waveforms as indicators of arterial properties and ventricular/arterial coupling. AB - The purpose of this experiment is to investigate the effect of arterial mechanics on carotid blood pressure and blood flow waveforms using an animal model. Blood pressure and blood flow waves were recorded from the carotid artery of the rabbit under different physiological and pharmacological conditions. The basic mechanism of the formation of pressure and flow waveforms was studied based on the anatomical structure and the mechanical properties of the arterial system. The interaction between the left ventricle and the arterial system was also discussed based on the carotid pressure and flow waveforms. PMID- 8205494 TI - Preference for the Diskhaler rather than the metered dose inhaler in patients with airway obstruction. AB - A powder system, the Diskhaler inhaler (DI) has been developed to overcome the limitations of the metered dose inhaler (MDI) in the treatment of obstructive airway diseases. Seventy-three patients were enrolled in this prospective study to compare these 2 modes of treatment. The first 2 weeks involved using the DI and the second 2 weeks the MDI. We found that the Diskhaler was easy to learn to use with a success rate of 68.0% on the first attempt, and 100% by the third. Only 4.8% patients could not perform the whole procedure perfectly two weeks later, compared with a 9.5% failure rate with the MDI. The use of the DI did not result in hand-breathing coordination problems as found in 25% of MDI users. After two weeks of use, 65.6% preferred the Diskhaler (P < 0.001), 89.1% felt it was more convenient to use (P < 0.001), and 85.1% felt it was easier to carry around (P < 0.01) compared with previous devices used. Among the 52 patients who completed the study using both inhalers, more patients (92.3%) using the DI were able to use the device correctly than those using the MDI (65.4%). After 2 weeks of use, 100% of the Diskhalers were still working, and 85.0% were kept clean. The only problem encountered was that 0.2% of the blisters had not been punctured appropriately. This should be emphasized when teaching the patients. In conclusion, the Diskhaler is easier to learn, simpler to manipulate and more convenient to use resulting in an increased patient compliance. It is also environmentally a better choice for inhalation therapy. PMID- 8205496 TI - Traumatic patellar tendon ruptures--a follow-up study of primary repair and neutralization wire. AB - Thirty-five patients with traumatic patellar tendon ruptures treated with primary repair and neutralization wire were retrospectively reviewed. The length of follow up ranged from 1.5 years to 5 years with an average follow up period of 20 months. All the ruptures occurred due to acute trauma, twelve of them (34%) involved in a multiple injuries, and nineteen had an open wounds around the knee joints. The diagnostic clues included a high riding patella by palpation or by X ray, hemoarthrosis, a palpable gap over the tendon; and being unable to extend the knee actively. Using the criteria of Siwek and Rao, at follow up 57% were rated as excellent, 28.6% good; and 14.2% unsatisfactory. None of the 35 patients had a rerupture of tendon. It is recommended that primary repair with a neutralization wire can be a treatment of choice for traumatic patellar tendon ruptures. PMID- 8205495 TI - Insulinoma--clinical experience in ten cases. AB - During the period between January 1981 and December 1992, a total of ten patients with pathologically confirmed insulinoma were studied. All patients presented with variable degrees of neuroglycopenic symptoms and Whipple's triad. The ratio of insulin to glucose after an overnight fast was greater than 0.3 in 90% (9/10) of patients. Eight patients who received supervised fasting developed neuroglycopenia with relative hyperinsulinemia within 48 hours of fasting. Four of 8 patients developed hypoglycemia during a 5-hour oral glucose tolerance test (OGTT). Calcium infusion test was more sensitive in patients with an initially higher plasma glucose. The detection rates of various localization studies were 12.5% (1/8) by abdominal ultrasonography, 37.5% (3/8) by abdominal CT scan, 50% (5/10) by selective superior mesenteric and celiac arteriography. Transhepatic portal venous sampling (THPVS) detected insulinomas in 4 of 4 cases. Endoscopic ultrasonography and intraoperative ultrasonography were performed on 1 and 2 cases respectively, and were able to localize the lesions successfully. All patients received surgical treatment including enucleation (n = 2), subtotal pancreatectomy (n = 3) and distal pancreatectomy (n = 5). All patients had single tumors which were all benign islet cell adenomas. The mean size of the tumors was 15.5 +/- 2.0 mm in diameter (range: 8 to 30 mm) and mainly located in the body (50%) and tail (40%), only 1 in the pancreatic head. All symptoms of hypoglycemia subsided after operation. Hyperglycemia was observed in all patients immediately after operation, and most of them resumed normoglycemia within 8 days. However, the 2 patients who had impaired OGTT preoperatively had persistent hyperglycemia after operation and therefore were diagnosed as having diabetes (NIDDM). PMID- 8205497 TI - [Measurements of the lumbar spinal canal of Chinese by computed tomography]. AB - The study of the lumbar canal sizes in Chinese has not been reported before. Thirty adult patients, aged 20 to 40 years, who sustained thoracolumbar or lumbar fracture-dislocation and needed further computed tomographic (CT) scanning were included in this study. There was no significant back pain or sciatica on these patients before. Measurements of the med-sagittal anteroposterior (A-P) and interpedicular (I-P) diameters of the spinal canals L1 to L5 were requested at the same time during CT scanning. The results show that the lowest normal limits of the A-P and I-P diameters of the lumbar canals in Chinese are 11 mm and 19 mm respectively. The I-P diameters increase progressively from the first to the fifth vertebrae. The A-P diameters, however, are more variable and shortest at L2, L3 and L4 vertebrae. PMID- 8205498 TI - [Evaluation of factors affecting nutritional assessment based on anthropometric data of Chinese undergoing health screening in Taiwan]. AB - This study is aimed at the establishment of anthropometric data in normal Chinese undergoing health screening in Taiwan, in order to provide reference values for nutritional assessment and to compare them with those standard values of the Western population. Seven hundred and thirty-two Chinese who underwent health screening in Chang Gung Memorial Hospital at Linkou (1981-1984) and at Kaohsiung (1986-1988) were enrolled in the study. These included 394 male Chinese and 338 female Chinese whom were considered normal in nutritional status and who did not have diabetes mellitus, tuberculosis, malignancy, liver and renal disorders, as well as those with hypoalbuminemia of unknown etiology. The following parameters were examined: body height (BH), body weight (BW), triceps skin fold (TSF), midarm circumference (MAC), midarm muscle circumference (MAMC), serum albumin and total lymphocyte count (TLC). The results revealed that: (1.) Besides a lower BH and BW, the 50th percentile for TSF in female Chinese fell between 50th-25th percentile of the Western women. As for the males, the Chinese fell below 50th percentile for TSF of the Western population of the same age and sex groups; (2.) The 50th percentile for MAMC in Chinese of both sexes fell below the 25th percentile of the Western population of the same age and sex groups; (3.) Aside from normal ranges, the serum albumin level decreased significantly with increasing age. Such a change was not found in TLC. This study stressed the difference in anthropometric data in terms of race and age and the importance of assessing patients' nutritional status by making reference to the standard value of their pertinent population and age group. PMID- 8205499 TI - [The clinical history of midtrimester low placentation]. AB - The finding of low implantation of placenta during midtrimester is not uncommon. It does not constitute an immediate obstetric emergency, but rather demanding serial and thorough follow-up. Previous uterine trauma and scarring caused by Caesarean section is a significant predisposing factor, while the roles of maternal age, gravidity, parity, sex of newborn are controversial. Placenta previa patients have a tendency to develop antepartum hemorrhage and preterm labor. Neither IUGR nor congenital malformations are associated abnormalities in our study. The rate of cesarean section in patients with placenta previa has increased, but the risk of perinatal morbidity has not increased. "Migration" means the dynamic relationship between the placenta and internal O.S., which occurred in 79.6% cases overall, especially in the subgroup of low-lying and marginal placenta previa. The "migration" does not protect patients from operation, nonetheless, the defined "placenta previas" are not all destined to cesarean section. Ultrasonography is a helpful diagnostic tool, via abdominal or vaginal route, and is a practical guide of expectant management. PMID- 8205500 TI - Congenital cutaneous candidiasis--report of two cases. AB - Candida infection contracted in utero and manifested at birth is a rare event. Two newborn infants are presented with generalized maculopapular rashes at birth. The eruption soon became vesicles or pustules; no other manifestations were found. Candida albicans was isolated from the skin lesion. After topical antifungal application, the lesions became fine and desquamated in the recuperative period. No complication was noted during the course. The diagnosis of congenital cutaneous candidiasis relies on its clinical course and positive culture result of the skin lesion. No systemic antifungal therapy is recommended except for the high risk infants. PMID- 8205501 TI - Long term survival of a patient with a regressed giant hepatocellular carcinoma after transcatheter hepatic artery embolization (TAE) complicated with liver abscess. AB - A 62-year-old male patient with histologically proven hepatocellular carcinoma, received transcatheter hepatic artery embolization (TAE) therapy. Development of right pyothorax and liver abscess at the tumor region occurred 4 months later after TAE. Aeromonas hydrophila was isolated from the liver abscess. After repeated percutaneous drainage, the abscess cavity disappeared and the tumor became undetectable by ultrasonography. Nineteen months after the initial presentation, a second tumor at the dome of the right lobe liver was found. TAE was repeated. Bile stasis with stricture of left intrahepatic ducts were found by Tc-99m HIDA cholangiography and endoscopic retrograde cholangiography. The patient had a normal lifestyle until the third tumor appeared at the right lower liver 18 months after the second TAE. TAE was conducted a third time. A shunting between the hepatic artery and vein developed at the new tumor area 3 months later. The patient is surviving today which is five and a half years after the initial diagnosis. We believe that the liver abscess after TAE contributed to the complete regression of the giant tumor, in addition to the anti-tumor effect of the successful TAE. PMID- 8205502 TI - Photodisruption of deposits on intraocular lens by Nd: YAG laser a case report. AB - After cataract surgery with intraocular lens (IOL) implantation, there is usually inflammation with deposits on IOL. In rare cases, the deposit may be severe even after medical treatment and require removal by laser or surgery. The case is a 71 year-old woman who received cataract surgery 8 years ago. She had numerous inflammatory deposits on the anterior surface of IOL in the left eye. After photodisruption by Nd:YAG laser with Q-switched/fundamental mode/0.5 mJ/1 pulse per burst/0 defocus/65 bursts and focus on deposits with contact lens, the deposits were cleaned without any complication and the patient's vision improved. PMID- 8205503 TI - Successful treatment of male infertility due to hypogonadotropic hypogonadism- report of three cases. AB - Exogenous gonadotropins or pulsatile gonadotropin-releasing hormone is now most commonly used to treat male infertility due to hypogonadotropic hypogonadism. We report three cases of hypogonadotropic hypogonadism with variable etiologies and presentations who were successfully treated with exogenous gonadotropins and/or testosterone for their infertility. The diagnosis and clinical presentations of these three patients are summarized as follows. The first patient was a case of Kallmann's syndrome presented with short stature, infantile genitalia and anosmia. The second patient was a case of idiopathic hypogonadotropic hypogonadism presented with small genitalia and impotence. The third patient was a case of acquired hypogonadotropic hypogonadism due to pituitary adenoma presented with impotence, cold intolerance and visual field defect. After adequate therapy with human chorionic gonadotropin, human menopausal gonadotropin and/or testosterone, the secondary male characteristics of these three patients improved and the fertility were all restored. PMID- 8205504 TI - Benign osteoblastoma of the spine--report of two cases. AB - Benign osteoblastoma is a rare spinal tumor, with the posterior element mainly involved. Symptoms do vary and there is a long diagnostic delay, especially in young people. We present two cases of benign osteoblastoma. One occurred in the atlas and presented with a painless neck mass. The other occurred in the lumbar spine with symptoms of long-term spinal pain and radicular pain. Preoperative Technetium bone scan and computed tomography (CT) resulted in exact localization and better operative planning. En bloc excision of tumor is indicated for complete pain relief and full return of spinal mobility. PMID- 8205505 TI - Buttock augmentation with silicone prosthesis--a case report. AB - A 18-year-old male patient presented with small, flat buttock due to gluteus maximus contracture which caused psychological problem. Bilateral gluteal augmentation was achieved with tissue expanders followed by permanent silicone prosthesis replacement. A two year postoperative follow up revealed no capsular contracture of the prosthesis and no limitation of the patient's activities. The improved contour has improved the patient's outlook on his body image or confidence in his body image. PMID- 8205506 TI - Gallbladder adenocarcinoma with gallstone and calcified ova of clonorchis sinensis--a case report. AB - A case of gallbladder adenocarcinoma with gallstone and calcified parasitic ova of Clonorchis sinensis was described. The patient, a 58-year-old Chinese woman, presented with general malaise and jaundice. The gallbladder contained 3 stones in addition to the cancerous lesion. Microscopically, we saw calcified parasitic ova of Clonorchis sinensis associated with the stones. The relationships between Clonorchis sinensis, stones and adenocarcinoma were discussed. PMID- 8205507 TI - Development of the functional orthosis. AB - In conclusion, a functional orthosis may be used to effectively treat most, but not all, abnormalities of the lower extremity that cause abnormal function of the foot. Abnormalities that are resistant to treatment with functional orthoses are compensated talipes equinus, excessive verticality of the oblique axis of the midtarsal joint, forefoot adductus that exceeds 15 degrees of adductus, Charcot's disease, congenital shortage of the iliopsoas muscle, and certain neurologic diseases that exhibit transient muscle spasm or paralysis, resulting in abnormal forces acting upon the foot that vary with time. Unfortunately, laboratories that claim to fabricate functional orthoses may turn out products that vary from nondescript arch supports to orthoses that only partially control function of the foot. The author hopes the practitioner who reads this article will be better able to evaluate whether his or her laboratory is providing his or her patient with a functional orthosis when one is ordered. PMID- 8205508 TI - The use of gait plates for in-toed and out-toed deformities. AB - One of the most common pediatric abnormalities treated by podiatrists is an angle of-gait disturbance. Prior to the initiation of treatment, it is imperative that the practitioner determines both the cause and extent of the problem. At this point, the practitioner will be able to determine what the most appropriate treatment should be. In-toe and out-toe gait plates provide an effective manner of altering a developing youngster's angle-of-gait problems and are capable of allowing the child to function and develop in a more normal fashion. PMID- 8205509 TI - Various types of orthoses used in podiatry. AB - Deciding which orthosis would be best suited for a given patient is a complex process involving many different factors. The fancy names used by laboratories to describe their products only add to the confusion when the practitioner is attempting to determine the best device. The ability to successfully manage biomechanical abnormalities may be enhanced by understanding the properties of different orthotic materials and the associated patient factors involved. The podiatric practitioner also should be aware that the grade and quality of materials are not the same from different manufacturers, and that the way laboratories handle the materials also affects the final properties of the orthosis. For this reason, it is beneficial to sample orthoses from various laboratories, and to feel comfortable in asking for technical assistance when ordering. PMID- 8205510 TI - Historical review and current use of the Whitman/Robert's orthoses in biomechanical therapy. AB - Current literature disputes Whitman's belief that muscle action plays the primary role in foot stability. Because of this faulty premise, Whitman included an excessively high medial flange in his orthosis. The high medial flange caused many patients a great deal of discomfort. To avoid this pain, the patients would not wear the brace, and as a result, it had little clinical value. For this reason, podiatrists seldom use the Whitman/Robert's orthosis unless it has been modified. Although Whitman constructed his brace under a false premise, it provided current researchers with a great deal of valuable information. Many aspects of the current foot orthosis were derived from Whitman's original work. The medial heel skive, for example, is very similar in function to the extrinsic varus wedging used by Roberts and the Thomas heel wedge used by Whitman. The Blake inverted orthotic also displays some conceptual similarities to the seldom used Whitman/Robert's brace. Consequently, although Whitman did not fully appreciate the mechanisms that stabilize the foot, there is no question that his efforts had a profound effect upon the development of modern functional foot orthoses. PMID- 8205511 TI - A review of the biomechanics of shoes. AB - This article reviews the basic mechanics of rotations and motions and applies them to various characteristics of shoe design. What is known about the biomechanical consequences of midsole cushioning, midsole geometry, and flexibility is reviewed and some advice for clinicians in helping their patients choose shoes is given. PMID- 8205512 TI - Custom shoe therapy. Current concepts, designs, and special considerations. AB - Custom orthopedic shoes represent the ultimate combination of function and aesthetics. Incorporating biomechanics and craftsmanship, shoes can redistribute weight, restrict joint motion, facilitate ambulation, and decrease the probability of neuropathic ulceration. Despite these advantages, many podiatrists know little about shoe therapy and consequently underuse it. This article describes the various types of therapeutic shoe modalities available and presents a systematic method of their application. Some of the latest developments in technology and health care reform also are revealed. PMID- 8205513 TI - Applications and use of in-shoe orthoses in the conservative management of Charcot foot deformity. AB - Charcot joint arthropathy is one of the more challenging entities encountered by the podiatric physician. The primary goal of treatment is to preserve skin integrity. A secondary goal is to provide a stable extremity for ambulation. The ultimate goal is to improve the quality of life for these individuals. The ability to accomplish these goals by conservative means requires a knowledge of biomechanics as well as orthoses and shoe gear. Perseverance, compassion, and a little creativity often are helpful as well. PMID- 8205514 TI - Clinical methods for predicting the effectiveness of functional foot orthoses. AB - The author has proposed a method of evaluation for predicting the effectiveness of functional foot orthoses to significantly alter foot motion of the excessively pronating or pronated foot during gait. This is not a method to determine when symptomatic relief will occur because pain secondary to poor foot mechanics usually is relieved prior to obvious gait alterations. An accurate prognosis based on structural geometry and intrinsic stability is important when deciding between surgery and purely mechanical therapy to alter foot mechanics. PMID- 8205515 TI - A conceptual look at rearfoot motion. AB - A conceptual look at rearfoot motion and the interaction of the axes of the rearfoot is presented. The importance of midtarsal joint stability is discussed, and a question is raised as to what creates stability in the midtarsal joint. Finally, the nature of orthosis function and the effect these devices have on the midtarsal joint for stability and function are discussed. PMID- 8205516 TI - New techniques to establish the subtalar joint's functional axis. AB - A new technique to establish the functional subtalar joint axis in live models is presented. Previous studies had a poor reference to the body planes because they relied on cadaver bone models and were not referenced to actual live function. The lower value for the function axis is due to the response of the midtarsal joint and forefoot to loading and ground reactive forces. The techniques were applied to the clinical setting by establishing a reference line on lateral RCSP radiographs and calculating the actual axis to this reference line. The axis deviated from the reference line by a small range (4 degrees) and can be corrected by reference to the calcaneal inclination angle for high or low angular differences. This simple technique can be used clinically to determine axial changes that may be required for surgical procedures and for evaluating the effect of orthosis control. PMID- 8205517 TI - Update and rationale for the inverted functional foot orthosis. AB - The inverted orthotic technique, also known as the Blake functional foot orthosis, is a prescription variable that allows for greater control of abnormal foot function. This article describes the indications for this prescription and the specific stability changes this technique produces. The authors conclude that it is crucial for laboratories to be brought into the process of orthosis development so that new techniques can be incorporated easily into therapy. PMID- 8205518 TI - Pressure-removing strategies in neuropathic ulcer therapy. An alternative to total contact casting. AB - Technical considerations, advantages, and disadvantages of felt and foam contact pads have been presented. Anecdotally, it appears the technique provides a more dynamic, safe, and practical method of ulcer decompression compared with total contact casting. In light of the apparent advantages of felt and foam contact padding, a randomized prospective study would be worthwhile to determine the effectiveness of this modality as compared with total contact casting. PMID- 8205519 TI - The center of pressure index in the evaluation of foot orthoses in shoes. AB - The objective and quantitative measurement of the effect of orthoses on the foot is important in evaluating orthosis design, negative casting techniques, orthosis materials, and relative clinical outcomes. The center of pressure pattern is the centroid of the pressure distribution at a series of moments in time as ground reaction is applied over the plantar surface of the foot. This article describes methods to obtain this index and how to apply this information to the evaluation of foot orthoses. PMID- 8205520 TI - Suppression of tumorigenicity of human prostate cancer cells by introduction of human chromosome del(12)(q13). AB - The introduction of normal chromosomes into tumor cells by microcell fusion mediated transfer is a powerful technique to identify putative tumor suppressor genes. We have used this approach to independently transfer human chromosomes 3 and 12 into a human prostate cancer cell line, DU 145. We showed that while the extra copy of chromosome 3 had no effect on the in vivo tumorigenicity of these cells, microcell hybrids containing an introduced portion of chromosome 12 (12pter-12q13) exhibited complete suppression of tumorigenicity in athymic nude mice. The presence of a dual selectable marker facilitated the selection for cells having segregated del(12)(q13). Loss of this fragment in three different clones led to reexpression of the malignant phenotype. These results demonstrate that one or more genes on human chromosome 12 function as tumor suppressors of prostate carcinogenesis. PMID- 8205521 TI - Effects of hypoxia on detoxicating enzyme activity and expression in HT29 colon adenocarcinoma cells. AB - Resistance of hypoxic tumor cells to ionizing radiation and cytotoxic drugs has been attributed to changes in the reactivity and/or the half-times of reactive species in the altered redox environment. Exposure of eukaryotic cells to such hypoxic conditions results in the induction of the synthesis of several unrelated proteins. To investigate further the phenomenon of hypoxic cell resistance to cytotoxic drugs, we examined the effects of hypoxia on the expression of a group of enzymes involved in drug metabolism. Exposure of HT29 colon carcinoma cells to hypoxia resulted in a marked increase in the activity of DT-diaphorase and in glutathione content. The activity of glutathione transferase was not increased by this treatment. The response was proportional to the duration of hypoxia. After the cells were exposed to hypoxic conditions for 8 h, followed by restoration of an oxic environment, the elevation in enzyme activity and glutathione content reached a peak at 48 h (40 h after the restoration of an oxic environment) and returned to baseline at 72 h. Elevation of steady-state levels of DT-diaphorase and gamma-glutamylcysteine synthetase mRNA followed a similar time course, with > 10-fold increases over oxic cells at 24 h. The elevation of DT-diaphorase mRNA content was found to result both from transcriptional induction and from increased message stability. The magnitude and persistence of elevated detoxicating enzyme activity following a relatively short hypoxic exposure followed by reoxygenation suggest a novel potential mechanism of resistance to cytotoxic drugs in hypoxic tumors. PMID- 8205522 TI - A negative regulatory factor is missing in a human metastatic breast cancer cell line. AB - The intermediate filament protein, vimentin, is differentially expressed in various tissues and stages of development and in metastatic versus nonmetastatic breast cancer cell lines. Previously, we have shown vimentin expression to be regulated at least in part by a silencer element which binds a M(r) 95,000 protein and an overriding, antisilencer element which binds a M(r) 140,000 protein. Southwestern blot (DNA-protein) analyses indicate that silencer protein binding activity is missing in the metastatic breast cancer cell line (MDA-MB 231), where vimentin is highly expressed, but is present in the nonmetastatic breast cancer cell line, MCF-7, where vimentin is not expressed. This suggests that the absence of a functional silencer protein may lead to expression of vimentin as well as other genes which contribute to the metastatic state. PMID- 8205523 TI - Pharmacokinetics of the in vivo and in vitro conversion of 9-nitro-20(S) camptothecin to 9-amino-20(S)-camptothecin in humans, dogs, and mice. AB - We have determined that 9-nitro-20(S)-camptothecin (9NC) converts to 9-amino 20(S)-camptothecin (9AC) in humans, dogs, and mice. Following a single oral dose of 0.1 mg/kg of 9NC, the human plasma concentration reached a maximum concentration of 483 ng/ml at 3.4 h with an area under the curve (AUC) of 2.6 micrograms.h/ml and a half-life of 2.5 h. As conversion of 9NC to 9AC occurred, the maximum calculated concentration of 9AC was 14.0 ng/ml at 10.3 h with an AUC of 311 ng.h/ml and a half-life of 7.1 h. Following a single oral dose of 1.0 mg/kg of 9NC, the maximum concentration of 9NC in the human volunteer was 1247 ng/ml at 5.3 h with an AUC of 17194 ng.h/ml and a half-life of 4.9 h. In this human, the Cmax of 9AC was 208 ng/ml at 17.2 h; the AUC was determined to be 9121 ng.h/ml, and the half-life was 13.1 h. In a dog after a single oral dose of 1.0 mg/kg 9NC, the maximum concentration for 9NC was 19.1 ng/ml at 0.7 h with a half life of 6.4 h and an AUC of 186 ng.h/ml. The maximum concentration of 9AC in this dog was 9.2 ng/ml at 2.9 h with an AUC of 310 ng.h/ml and a half-life of 21.1 h. The maximum concentration of 9NC in the mouse after a single oral dose of 4.1 mg/kg of 9NC was 732 ng/ml at time 0.1 h with an AUC of 441 ng.h/ml and a half life of 10.0 h. The maximum concentration of 9AC in the mouse was 26 ng/ml at 0.6 h. The AUC was 63 ng.h/ml, and the half-life was 1.2 h. Incubation of mouse liver, spleen, kidney, brain, and muscle tissue with 9NC all indicated conversion to 9AC, yet no conversion was observable in cell-free plasma from human or mouse blood. Structural identification of 9AC was confirmed by mass spectrometry. PMID- 8205524 TI - Wilms' tumor suppressor gene expression in rat and human mesothelioma. AB - Induction of mesothelioma in the rat is an important animal model for assessing the carcinogenic potential of fibers and for understanding the molecular basis underlying the development of these tumors. Mesotheliomas and nephroblastoma (Wilms' tumor) have many developmental, biochemical, and histological similarities; however, the expression of the Wilms' tumor suppressor gene, WT-1, has not been well characterized in the rat, and its expression pattern in rat or human mesothelioma has not been described. We report that WT-1 transcripts (3.2 kilobases) could be detected by Northern analysis in adult rat testis, spleen, kidney, lung, heart, and glomerular mesangial cells. Normal adult mesothelial cells also expressed this gene. Rat mesothelioma cell lines expressed WT-1 transcripts of 3.2 kilobases and an additional 2.8-kilobase transcript, previously only reported to be expressed in the testis. Normal and transformed rat mesothelial cells expressed all four of the WT-1 splice variants, except testis, which only expressed WT-1 splice variants containing exon 5. Seven of seven human mesothelioma cell lines examined also expressed WT-1 transcripts, suggesting that expression of this gene may be useful in the diagnosis of these tumors. PMID- 8205525 TI - Amplification and overexpression of the cyclin D1 gene in aggressive human hepatocellular carcinoma. AB - We analyzed the genetic alterations of the cyclin D1 and INT-2 genes in hepatocellular carcinomas (HCCs) from 45 patients. Among these, expression of the cyclin D1 mRNA was also analyzed in 18 of them by Northern blotting. The cyclin D1 gene was amplified 3-16 fold in five HCCs (11%); among these, the INT-2 gene was also amplified 2-10 fold in four HCCs. We analyzed the mRNA of cyclin D1 in four HCCs with gene amplifications, and 6-10 fold overexpressions were detected in all of them. Because the cyclin D1 gene was amplified in patients at an advanced stage of HCC with rapid tumor growth, it appeared to be associated with the aggressive behavior of tumors. Studies on loss of heterozygosity on chromosome 13q, where the retinoblastoma (RB) gene is located, indicated that all HCCs with an amplified cyclin D1 gene retained heterozygosity on chromosome 13q. These results suggest that amplification and overexpression of the cyclin D1 gene result in the rapid growth of a subset of HCC, even though the function of the RB gene is retained. PMID- 8205526 TI - Loss of heterozygosity for 10q22-10qter in malignant melanoma progression. AB - Karyotypic and molecular data indicate that genetic events involving the chromosome region 10q22-10qter may be related to tumorigenesis in malignant melanoma. To test this we analyzed 10 polymorphic microsatellite repeats in the region 10q22-qter, using a polymerase chain reaction-based assay for loss of heterozygosity and DNA isolated from normal and tumor tissue from 26 individuals with malignant melanoma. The samples included 19 paired normal and malignant tissues representing various stages of melanoma as well as 7 cases in which samples from at least 2 different points in time during tumor progression were available. Our findings indicate that loss of heterozygosity of 10q22-10qter is a frequent event, that the observed loss of heterozygosity does not result from whole chromosome loss, and that it is associated with tumor progression. Finally, the appearance of new alleles in two of the tumors may indicate the involvement of DNA replication errors in melanoma analogous to such events in other tumor types. PMID- 8205527 TI - Inverse relation of E-cadherin and autocrine motility factor receptor expression as a prognostic factor in patients with bladder carcinomas. AB - Down-regulation of E-cadherin, an intercellular adhesion molecule, and up regulation of autocrine motility factor receptor (gp78) expressions have been shown to play a role in tumor cell invasion and metastasis. Monoclonal antibodies against E-cadherin and gp78 were used to stain serial snap-frozen sections of 12 normal bladder and 83 bladder carcinoma specimens (27 noninvasive, 53 invasive, and 3 metastases). In normal urothelium, E-cadherin is expressed while gp78 is not. Positive expression of E-cadherin and negative expression of gp78 were found to be associated with a low risk of clinical progression in the superficial bladder carcinoma patient group. While reduction in E-cadherin concomitantly with an increase in gp78 expression was associated with poor prognosis, 71% of the patients (n = 30) underwent rapid cancer progression, and 32% of the patients died of cancer-related disease at a median of 2 years after initial diagnosis. Thus, it is suggested that reduction of E-cadherin expression associated with an increase in the level of gp78 in bladder cancers may define a high risk group of patients. The dual use of these two antigens may improve early diagnosis of high risk bladder cancer patients and influence treatment decisions. PMID- 8205528 TI - Recognition of tyrosinase by tumor-infiltrating lymphocytes from a patient responding to immunotherapy. AB - The observation that allogeneic melanoma cells matched for particular HLA class I alleles stimulate T-cells isolated from patients suggests that widely shared antigens exist on these tumors. A transient expression system was developed for screening a melanoma complementary DNA library using the highly transfectable human kidney cell line 293. Using this system, large numbers of complementary DNA clones can be rapidly screened for the expression of antigens which stimulate T cells. Tumor-infiltrating lymphocytes from patient 888, which recognized melanoma in the context of HLA-A24, were used to screen a complementary DNA library made from the autologous melanoma. Our results demonstrate that these tumor infiltrating lymphocytes recognize tyrosinase, a gene previously shown to be recognized by T-cells only in the context of HLA-A2. These data demonstrate that a single antigen can be recognized in the context of two different class I HLA alleles. In addition, this study suggests that recognition of tyrosinase by antigen-specific T-cells may be involved in tumor rejection. PMID- 8205529 TI - A common region of homozygous deletion in malignant human gliomas lies between the IFN alpha/omega gene cluster and the D9S171 locus. AB - Deletions of the 9p-localized type-I interferon (IFN) genes and adjacent loci often occur during the development of malignant glioma. We have applied restriction fragment length polymorphism and microsatellite analysis to 12 loci covering this region of 9p and 3 loci on 9q in 74 human glial tumor tissues to define and further localize the smallest region of hemizygous or homozygous deletion common to the tumors. Three regions of homozygous deletion were evident among the panel of tumors; only one of these, however, residing between D9S171 and the IFN alpha/omega gene cluster, was involved in multiple cases (13 glioblastomas). Hemizygous deletion of this same region was observed in an additional 27 tumors. In total these data indicate the frequent inactivation of a novel tumor suppressor gene residing adjacent to and centromeric of the type-I IFN genes in malignant gliomas. PMID- 8205530 TI - Identification of a p53-dependent negative response element in the bcl-2 gene. AB - Recently, we have shown that the p53 tumor suppressor gene product can inhibit expression of the bcl-2 gene. In this report, we explored the molecular basis for p53-mediated down-regulation of bcl-2 gene expression using a cotransfection approach involving p53 expression plasmids and chloramphenicol acetyltransferase (CAT) reporter gene constructs containing regions from the bcl-2 gene. When transfected into a p53-deficient human lung cancer cell line H358, reporter gene constructs containing only the promoter region of bcl-2 and upstream sequences were not suppressed by p53. Inclusion of bcl-2 gene sequences corresponding to the 5' untranslated region in bcl-2/CAT constructs, however, resulted in p53 dependent down-regulation. A 195-base pair segment from the bcl-2 gene 5' untranslated region was found to be capable of conferring p53-dependent repression on a heterologous expression plasmid containing CAT under the control of an SV40 immediate early-region promoter. This p53-negative response element functioned in an orientation-independent manner when placed either upstream or downstream of the SV40-CAT transcription unit. The results demonstrate the existence of a negative response element in the bcl-2 gene through which p53 may either directly or indirectly transcriptionally down-regulate expression of this gene involved in the regulation of programmed cell death. PMID- 8205531 TI - Staurosporine blocks cell progression through G1 between the cyclin D and cyclin E restriction points. AB - The protein kinase inhibitor staurosporine (SSP) stops progression of normal nontransformed cells in the G1 phase of the cell cycle. This implies that at least one of the cell cycle associated kinases, essential for cell transit through G1, is sensitive to SSP. Using multivariate flow cytometry to correlate the expression of cyclin E or cyclin D with cellular DNA content (i.e., cell cycle position), we have presently characterized the point of action of SSP in relation to the expression of these cyclins. During stimulation of normal human lymphocytes by phytohemagglutinin, cyclin D was expressed early, peaking at 8-14 h, while cyclin E appeared later, reaching a maximum at the time of cell entrance to S phase (24 h). Addition of SSP at the time of cell stimulation, while markedly suppressing the expression of cyclin E, had a rather modest effect on the expression of cyclin D. The data indicate that the SSP sensitive kinase(s) involved in cell progression through G1 operate beyond the restriction point of cyclin D but prior to that of cyclin E. Thus, the target(s) of SSP is (are) either the p33cdk/cyclin E complex itself or other protein kinase(s), activated subsequent to the cyclin D but prior to the cyclin E restriction point, the activity of which is essential for cell transit through G1. PMID- 8205532 TI - Induction of tamoxifen-4-hydroxylation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), beta-naphthoflavone (beta NF), and phenobarbital (PB) in avian liver: identification of P450 TCDDAA as catalyst of 4-hydroxylation induced by TCDD and beta NF. AB - Tamoxifen has been found to be metabolized by liver primarily into three metabolites, tamoxifen-N-oxide, formed by the flavin-containing monooxygenase, and N-desmethyl- and 4-hydroxytamoxifen, formed by cytochrome P450. The N demethylation was demonstrated to be catalyzed by P4503A in rat and human liver; however, the P450s catalyzing the 4-hydroxylation have not been identified. Although 4-hydroxytamoxifen exhibits more potent estrogen agonist/antagonist activity than tamoxifen, the relative contributions of the parent drug and its 4 hydroxy metabolite(s) to the activity of tamoxifen in vivo have not been established. We report here that the rate of tamoxifen 4-hydroxylation is higher in livers of adult chicken and chick embryos than in livers of mammalian species. Tamoxifen 4-hydroxylation was increased by treatment of chick embryos with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), beta-naphthoflavone (beta NF), and to a lesser extent by phenobarbital (PB). The major effect of PB treatment was an increase in tamoxifen N-demethylation. Tamoxifen 4-hydroxylase activity of reconstituted purified chicken P450s was highest for TCDDAA, a P450 active in arachidonate epoxygenation and estradiol 2-hydroxylation, and one of the two major P450s induced by TCDD and beta NF in chick embryo liver. The second P450, TCDDAHH, which is active in aryl hydrocarbon hydroxylase and 7-ethoxyresorufin deethylase was inactive in tamoxifen 4-hydroxylation. Anti-TCDDAA IgG immunoinhibited tamoxifen 4-hydroxylation in microsomes from beta NF-treated embryos by over 80%, but was ineffective against this reaction in the controls. The immunochemical findings together with the reconstitution data identify TCDDAA as the P450 responsible for TCDD/beta NF-induced tamoxifen 4-hydroxylation in chick liver. In PB-treated livers, a P450 fraction containing CYP2H1/H2, the major PB-induced P450s, had the highest tamoxifen 4-hydroxylase and N-demethylase activities, a finding compatible with one or both of those P450s being responsible for the PB-induced tamoxifen 4-hydroxylation and N-demethylation. The findings reported here raise the possibility that exposure of women undergoing tamoxifen therapy to agents that induce human CYP1A2 or CYPB1/2 analogues may produce increased levels of 4-hydroxytamoxifen and that this may affect the therapeutic potency of tamoxifen. PMID- 8205534 TI - Dysregulation of epidermal growth factor receptor expression in premalignant lesions during head and neck tumorigenesis. AB - The development of head and neck cancer, believed to result from field cancerization and a multistep process of tumorigenesis, is often associated with an accumulation of genotypic and phenotypic alterations. The phenotypic changes could be the result of dysregulation of growth control genes such as epidermal growth factor receptor (EGFR). With the goal of identifying a potential biomarker of the multistep process of tumorigensis, we studied specimens of 36 head and neck squamous cell carcinomas from 5 different sites that contained normal epithelia and/or premalignant lesions adjacent to the tumors. Almost all of the individuals from whom these specimens were obtained had been exposed to first hand smoking and/or alcohol consumption. Using a monoclonal anti-EGFR antibody for immunohistochemical analysis on paraffin-embedded sections with attached 886 cells for internal control, the levels of EGFR expression were assessed by image analysis. The relative staining intensity of EGFR in normal epithelia adjacent to tumors was 2-fold higher than that in normal control epithelium (P = 0.021), suggesting that, even in histologically normal epithelium, EGFR was already up regulated in tissues surrounding tumors. These findings supported the theory of field cancerization in head and neck tumorigenesis. As tissue progressed from normal tissue adjacent to tumor to hyperplasia and to dysplasia, EGFR expression remained elevated. However, in the step from dysplasia to squamous cell carcinoma, EGFR expression was further and dramatically up-regulated (P = 0.01). Therefore, these results indicate that EGFR dysregulation happens in two steps, the moderate up-regulation of EGFR expression in normal epithelium adjacent to tumor and the further up-regulation of EGFR expression in the change from dysplasia to squamous cell carcinoma. In summary, the studies presented here indicate that EGFR dysregulation might be a useful marker for identifying individuals at risk of tumor development and an intermediate end point in chemoprevention trials. PMID- 8205533 TI - Colocalized alterations in connexin32 and cytochrome P450IIB1/2 by phenobarbital and related liver tumor promoters. AB - Direct intercellular signal transduction is achieved by the passage of small molecules through gap junctions (GJ). Previous studies in our laboratory showed that the liver tumor promoter phenobarbital (PB) reversibly decreases the abundance of the GJ protein connexin32 (Cx32) in both preneoplastic-altered hepatic foci and centrolobular hepatocytes (M. J. Neveu et al., Cancer Commun., 2: 21-31, 1990). Because the inhibitory effects of PB on GJ intercellular communication are prevented by the nonspecific cytochrome P-450 inhibitor SKF 525A (J. E. Klauning, et al., Toxicol. Appl. Pharmacol., 102: 533-563, 1990), we investigated whether alterations in Cx32 are coincident with changes in the major PB-inducible cytochrome P-450, termed b/e or IIB1/2. Immunostaining of liver cryosections from rats fed dietary PB demonstrated that centrolobular hepatocytes that exhibit reduced Cx32 express enhanced cytochrome P450IIB1/2 protein. In contrast, no change in the periportal distribution of connexin26 immunoreactivity was found in PB-treated rats. In addition, rats were treated with the structurally related barbiturates pentobarbital, amobarbital, barbital, and barbituric acid. We found that the extent of the hepatic lobule occupied by coincident centrolobular alterations in Cx32 and P-450 staining correlates with the ability of the compounds to promote liver oncogenesis. To determine the molecular mechanisms responsible for the modification in Cx32 staining, we examined the mRNA and protein levels of Cx32 and P450IIB1/2 in total-tissue homogenates from PB-treated rats. Northern blotting demonstrated thatdietary PB dramatically induced P-450IIB1 mRNA, but the same RNA samples failed to show alterations in Cx32 steady-state transcripts. Consistent with these findings, the level of Cx32 protein in total liver homogenates did not change in rats chronically fed PB. Examination of Cx32 solubility in 20 mM NaOH demonstrated that PB treatment results in the generation of a NaOH-soluble form of Cx32 (i.e., 47 kDa). In addition, trypsinized paraffin-embedded liver sections from PB treated rats exhibited diffuse cytoplasmic Cx32 staining that was restricted to centrolobular cells. Our results show that PB and related barbiturate tumor promoters reversibly down-regulate punctate Cx32 staining in centrolobular hepatocytes posttranslationally, possibly through modification(s) in the transport, assembly, and/or turnover of GJs. PMID- 8205535 TI - Increased formation of oxidative DNA damage, 8-hydroxydeoxyguanosine, in human livers with chronic hepatitis. AB - 8-Hydroxydeoxyguanosine (oh8dG) is a promutagenic DNA lesion produced by oxygen radicals. We examined alterations in the oh8dG level in human livers which have chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The oh8dG content in livers with chronic hepatitis was significantly higher than the oh8dG content in normal livers (P < 0.05). There was also a significant correlation between the oh8dG content in noncancerous liver tissues with individual serum alanine aminotransferase concentration (r = 0.515; P < 0.001). Thus, chronic inflammation in the liver produces oxidative DNA damage, which may increase the risk for genomic alterations causing hepatocarcinogenesis. PMID- 8205536 TI - In vivo enhancement of genomic instability in minisatellite sequences of mouse C3H/10T1/2 cells transformed in vitro by X-rays. AB - The level of genomic instability was determined during tumor development in vivo. Genomic rearrangements, a marker of genomic instability, was measured in mouse C3H/10T1/2 cells transformed in vitro by X-rays with a DNA fingerprinting assay. Three transformed clones isolated from type III foci were divided into two groups. Cells from the first group were injected s.c. into syngeneic and nonimmunosuppressed C3H mice. After 3 to 5 months, the tumors were excised, and the neoplastic cells were isolated and subcloned. Cells from the second group were incubated in vitro for 25 passages (about 6 months) to approximate the number of cell divisions occurring in the tumor, and then they were subcloned. DNA was extracted from subclones grown in vitro and in vivo and analyzed with the DNA fingerprinting assay. A high frequency of genomic rearrangements (50-100%) was found in subclones derived from tumors that arose in vivo, whereas the frequency was very low (< 10%) among subclones passaged in vitro, suggesting that genetic instability may be enhanced by factors present in the C3H mouse. In one clone (F-17) genomic instability appeared to be activated and down regulated. The high frequency of instability found in tumor cell subclones did not appear to result from an in vivo selection of a more tumorigenic subpopulation of cells present in the original clone prior to injection in the animal. This enhancement of genomic instability occurring in vivo could be required to complete the process of transformation to tumorigenicity and allow the neoplastic cells to adapt to a new environment. PMID- 8205537 TI - Functional insulin and insulin-like growth factor-1 receptors are preferentially expressed in multiple myeloma cell lines as compared to B-lymphoblastoid cell lines. AB - While IGF-1 plays a role in early B-cell development, little is known of insulin and insulin-like growth factor-1 (IGF-1) action in post-marrow B-cells. Recently, our laboratory demonstrated that mouse and human multiple myeloma (MM) cell lines possess functional insulin receptors (IRs) and IGF-1 receptors (IGF-1Rs). In this study, we show that responsiveness to insulin and IGF-1 is more developed in human MM cell lines than in human B-lymphoblastoid cell lines. Two human MM cell lines (U266 and RPMI 8226) were compared to three B-lymphoblastoid cell lines [Epstein-Barr virus immortalized B-cells (EBV), a Burkitt lymphoma cell line (Ramos), and a non-EBV lymphoblastoid cell line (HS Sultan)]. Surface IR and IGF 1R expression, measured by flow cytometry, demonstrated that the MM cell lines expressed more IRs and IGF-1Rs than did the EBV, Ramos, or HS Sultan cell lines. In vitro receptor kinase activity of affinity-purified receptors showed that the MM cells had more phosphorylated receptors than did the EBV, Ramos, or HS Sultan cells. Intracellular receptor signaling was also markedly different between the two cell groups. Whole cell phosphorylation studies showed that MM cells possessed not only hormone-dependent receptor autophosphorylation (M(r) 97,000) but also substrate phosphorylation (M(r) 185,000; 60,000). The lymphoblastoid cells, while demonstrating receptor autophosphorylation (IR autophosphorylation in the EBV cell line at 200 nM hormone was similar to MM receptor phosphorylation at 2 nM), lacked hormone-responsive substrates. The MM cell lines contained significantly more hormone-stimulated phosphatidylinositol 3-kinase (PI 3-kinase) activity than the B-lymphoblastoid cell lines. In the MM cells, PI 3-kinase was activated by at least 10-fold, but, in the B-lymphoblastoid cell lines, it was activated by no more than 2-fold. Hormone-responsive glucose metabolism was also greater in the MM cell lines. In the U266 cells, insulin increased lactate production 62 +/- 9 and 101 +/- 12% (mean +/- SE) at concentrations of 2 nM and 200 nM, respectively. IGF-1 produced 72 +/- 9 and 99 +/- 13% increases at similar concentrations. In the 8226 cells, insulin increased lactate production 4 +/- 4 and 36 +/- 15% at 2 and 200 nM, respectively. IGF-1 produced a 13 +/- 6 and 70 +/ 18% increase. In the EBV and Ramos cells, neither hormone increased lactate production by more than 10 +/- 3%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8205538 TI - Fermented dairy products, calcium, and colorectal cancer in The Netherlands Cohort Study. AB - Experimental studies suggest that an increased consumption of fermented dairy products and calcium might decrease the risk of colorectal cancer. The associations between fermented dairy products, dietary calcium, and colorectal cancer risk were investigated in a population with a wide variation in intake of dairy products. The Netherlands Cohort Study of diet and cancer started in 1986 when 120,852 Dutch men and women, ages 55-69, filled out a questionnaire concerning dietary patterns and lifestyle. The present analysis is based on 3.3 years of follow-up and includes 215 incident cases of colon cancer and 111 incident cases of rectal cancer, excluding cases diagnosed in the first year of follow-up. After adjustment for potential confounding variables, colorectal cancer risk was weakly inversely associated with the consumption of fermented milk [relative rate (RR) in the highest category of intake compared to nonusers, 0.89; 95% confidence interval (CI), 0.60, 1.33], unfermented milk (RR, 0.86; 95% CI, 0.57, 1.29), and cheese (RR, 0.88; 95% CI, 0.59, 1.33). However, category specific relative rates and tests for trends were not statistically significant. For fermented milk, the inverse association was limited to colon cancer (RR, 0.70; 95% CI, 0.43, 1.15; trend, P = 0.33). In crude and multivariate models, total dietary calcium intake (highest versus lowest quintile, RR, 0.92; 95% CI, 0.64, 1.34) and calcium from fermented dairy products (RR, 1.14; 95% CI, 0.77, 1.68) were not significantly associated with colorectal cancer risk. Calcium from unfermented dairy products was inversely associated with rectal cancer risk (RR, 0.55; 95% CI, 0.30, 1.04; trend, P = 0.03). After 3.3 years of follow-up, these data are not consistent with a substantially decreased risk of colorectal cancer with increased intake of fermented dairy products and dietary calcium. PMID- 8205539 TI - Mechanism of action of the antileukemic xanthone psorospermin: DNA strand breaks, abasic sites, and protein-DNA cross-links. AB - Psorospermin, a cytotoxic dihydrofuranoxanthone isolated from Psorospermum febrifugum, produced aberrant simian virus 40 DNA replication intermediates when added to lytically infected CV-1 monkey kidney cells. The aberrant viral intermediates showed dose-dependent DNA strand breaks and protein-DNA cross links, as well as decreased electrophoretic mobility. Simian virus 40 DNA from psorospermin-treated cells was shown to contain numerous abasic (apyrimidinic/apurinic) sites. The density of abasic sites was a function of the psorospermin dose. We conclude that psorospermin causes extensive loss of DNA bases in vivo. Primary amine groups of cellular proteins are known to react with abasic sites to form covalent protein-DNA cross-links and DNA strand breaks. Cytochrome c cross-linked spontaneously to viral DNA prepared from psorospermin treated cells but not to DNA from untreated cells. This suggests that the protein DNA cross-links and many of the DNA strand breaks observed in vivo result from reactions between abasic sites and chromosomal proteins. It is likely that the protein-DNA cross-links and DNA strand breaks contribute to the cytotoxicity and antineoplastic activity of psorospermin. PMID- 8205540 TI - Metabolism of bioreductive antitumor compounds by purified rat and human DT diaphorases. AB - The metabolisms of two standard electron acceptors and a series of bioreductive antitumor compounds by purified rat and human DT-diaphorases (DTD) were compared. DTD was purified from rat liver cytosol and from Escherichia coli in which rat liver or human lung tumor DTD complementary DNA was expressed. Km and kcat values for menadione and 2,6-dichlorophenolindophenol reduction were similar for the three enzyme preparations except that rat E. coli DTD had 2-3-fold higher kcat values for both menadione and 2,6-dichlorophenolindophenol and a 2-3-fold higher Km for menadione than either rat liver or human E. coli DTD. Reduction of the antitumor compounds was 1.9-4.9 times faster with rat E. coli DTD than with human E. coli DTD. The antitumor compounds were reduced in the following order by rat E. coli DTD: 2,5-dimethyl-3,6-diaziridinyl-1,4-benzoquinone > streptonigrin > mitomycin A > diaziquone > mitomycin C (MC) > 5-(aziridin-1-yl)-2,4 dinitrobenzamide. The order was the same for human E. coli DTD with one exception; diaziquone was reduced slightly faster than mitomycin A. Metabolism of doxorubicin could not be detected using rat or human E. coli DTD. MC-induced DNA cross-linking was also more efficient using rat E. coli DTD relative to human E. coli DTD. Metabolism of MC by rat and human E. coli DTD was also compared under aerobic and hypoxic conditions. Rates of reduction of MC and metabolite formation were similar under aerobic and hypoxic conditions, and the toxicity of MC to DTD rich HT-29 cells was also similar in aerobic and hypoxic conditions. In contrast, the toxicity of MC to DTD-deficient BE cells was potentiated markedly under hypoxia. These data show that although small catalytic differences between rat and human E. coli DTD can be observed, compounds such as 2,5-dimethyl-3,6 diaziridinyl-1,4-benzoquinone and streptonigrin are still excellent substrates for the human enzyme and may be useful in the therapy of tumors high in DTD activity. In addition, metabolism of MC by rat and human E. coli DTD was similar in aerobic and hypoxic conditions; in agreement with these data, cytotoxicity of MC to a DTD-rich cell line was oxygen independent. Increased MC cytotoxicity under hypoxia appears to be mediated by enzymes other than DTD. PMID- 8205541 TI - CGP 48664, a new S-adenosylmethionine decarboxylase inhibitor with broad spectrum antiproliferative and antitumor activity. AB - Inhibitors of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (SAMDC), derived from methylglyoxal-bis(guanylhydrazone) (MGBG), have been shown to have significant antitumor activity in several human solid tumor systems (U. Regenass et al., Cancer Res., 52:4712-4718, 1992). From an ongoing effort to synthesize derivatives with increased enzyme specificity and potency and improved antitumor efficacy, we have now identified CGP 48664, a 4 amidinoindan-1-one 2'-amidinohydrazone (J. Stanek et al., J. Med. Chem., 36:2168 2171, 1993). The compound displays potent inhibition of SAMDC (50% inhibitory concentration, 5 nM), modest inhibition of diamine oxidase (50% inhibitory concentration, 4 microM), and no detectable inhibition of ornithine decarboxylase. CGP 48664 inhibits the growth of a panel of human and mouse tumor cell lines, including one which expresses the multidrug resistance phenotype, with 50% inhibitory concentrations ranging between 0.3 and 3 microM. CGP 48664 does not seem to utilize the polyamine transport carrier system since it competes poorly with spermidine for uptake into L1210 cells (Ki 161 microM) and inhibits the growth of polyamine transport-deficient Chinese hamster ovary cells. Relative to MGBG or previously described MGBG analogues, CGP 48664 accumulates to much lower intracellular concentrations. Treatment of the L1210 cell for 48 h with 3 microM CGP 48664 decreases SAMDC activity to < 10% of control and initiates a compensatory 3-fold rise in ornithine decarboxylase. Consistent with SAMDC inhibition, putrescine pools increase 10-fold, whereas spermidine and spermine pools fall to < 10% of control. In contrast to MGBG, CGP 48664 displays attenuated antimitochondrial activity as indicated by a lack of effect on pyruvate oxidation and mitochondrial DNA levels under treatment conditions which inhibit cell proliferation. Specificity of drug action was indicated further by prevention of L1210 cell growth inhibition by exogenous spermidine or spermine. More convincingly, Chinese hamster ovary cells made approximately 1000-fold resistant by chronic exposure to the analogue were found to selectively overexpress SAMDC mRNA due to gene amplification. The new SAMDC inhibitor showed potent antitumor activity against syngeneic tumors (B16 melanoma and Lewis lung carcinoma) and nude mouse human tumor xenografts (T-24 bladder carcinoma, SK MEL 24 melanoma, and MALME-3M melanoma). On the basis of its novel structure, its apparent specificity of action, and its potent antitumor activity, CGP 48664 is the candidate drug for further preclinical development. PMID- 8205542 TI - Metabolism of 2',2'-difluoro-2'-deoxycytidine and radiation sensitization of human colon carcinoma cells. AB - Difluorodeoxycytidine (dFdCyd) is a new antimetabolite with clinical activity in patients with solid tumors but not leukemias. We have studied the metabolism, cytotoxicity, and radiosensitizing properties of dFdCyd in HT-29 human colon carcinoma cells. The results demonstrated that dFdCyd rapidly accumulated as the 5'-triphosphate dFdCTP in HT-29 cells, which was eliminated slowly in the absence of dFdCyd with a half-life of > 12 h. Accumulation of dFdCTP was associated with rapid depletion of cellular dATP pools. Exposure to the concentration that reduces cell survival by 50% of 30 nM dFdCyd decreased dATP levels by > 80% within 4 h. dGTP pools were depleted at higher concentrations of dFdCyd, whereas smaller decreases were effected in dTTP and dCTP pools. These results contrast with previous reports in leukemic cells which demonstrated that dFdCyd exposure depleted the endogenous dCTP pool to a greater extent than the dTTP, dATP, or dGTP pools. Based on these data, we suggest that the profound depletion by dFdCyd of dATP and dGTP pools in HT-29 compared to leukemic cells accounts for the superiority of this agent in solid tumors versus leukemias. Additional studies demonstrated that dFdCyd was a potent radiosensitizer in HT-29 cells. Maximal radiosensitization was observed when cells were irradiated immediately following dFdCyd exposure instead of prior to or in the middle of drug treatment. Radiation sensitization was dose and time dependent, with a noncytotoxic exposure to 10 nM dFdCyd for 24 h or 30 nM dFdCyd for 16 h producing a radiation enhancement ratio of approximately 2. Under these conditions, only the cellular dATP pool was depleted. When cells were exposed to higher concentrations of dFdCyd for 4 h, equivalent radiosensitization with a radiation enhancement ratio of 1.4 was obtained using 0.1, 1.0, or 10 microM dFdCyd. Despite a 15-fold increase in dFdCTP and depletion of dGTP and dCTP pools to < 25% of the control value with 10 microM compared to 0.1 microM dFdCyd, no increase in radiosensitization was observed. These results suggest that dATP depletion is an important factor in the radiosensitizing property of this promising new antitumor compound. PMID- 8205543 TI - Synergistic inhibition of T-lymphoblastic leukemic CCRF-CEM cell growth by gallium and recombinant human alpha-interferon through action on cellular iron uptake. AB - Gallium, a metal with clinical antineoplastic activity, is known to inhibit cellular iron uptake and iron-dependent DNA synthesis. Little information exists regarding the efficacy of gallium in combination with other agents. Since alpha interferon (IFN-alpha) can modulate the action of certain chemotherapeutic drugs, we examined its influence on the growth inhibitory effects of gallium in CCRF-CEM cells. IFN-alpha and gallium as single agents had only minimal to moderate antiproliferative effects. In combination, however, both drugs synergistically inhibited cell growth, causing cell death accompanied by DNA fragmentation. At lower concentrations (120 microM), gallium inhibited cellular iron uptake but did not increase transferrin receptor expression, nor did it block cellular proliferation. The addition of IFN-alpha to this concentration of gallium significantly increased the gallium-induced block of iron uptake, resulting in an increase in transferrin receptors and an inhibition of cell growth. In contrast, IFN-alpha did not enhance the effects of the iron chelator deferoxamine on iron uptake or cell growth. Our studies suggest that gallium and IFN-alpha synergistically inhibit DNA synthesis through a mechanism that includes inhibition of cellular iron uptake and depletion of intracellular iron below the critical level needed to maintain DNA synthesis. PMID- 8205544 TI - An antibody which specifically recognizes prelamin A but not mature lamin A: application to detection of blocks in farnesylation-dependent protein processing. AB - A polyclonal antibody [anti-prelamin A antibody (alpha-PA)] has been obtained against the peptide LLGNSSPRTQSPQN which is proteolytically removed during the farnesylation-dependent processing of prelamin A to mature lamin A. We tested the ability of this antibody to detect inhibition of farnesylation-dependent protein processing of prelamin A. The alpha-PA antibody was shown to immunoprecipitate prelamin A from lovastatin-treated HeLa cells but not mature lamin A from untreated cells. Further studies were performed after antigen-affinity chromatographic purification of the antibody. Western blotting of lovastatin treated HeLa cell extract demonstrated that the purified alpha-PA antibody recognizes prelamin A. Furthermore, this signal could be competed away by incubation with the peptide. Indirect immunofluorescence helped detect nuclear accumulation of the antigen in response to treatment of HeLa cells with lovastatin or in Chinese hamster ovary K1 cells transiently transfected with a prelamin A mutant blocked in farnesylation. This antibody should be useful for screening compounds that may block any of the three common steps in the farnesylation-dependent processing of proteins (farnesylation, endoproteolysis, and carboxymethylation) since it appears that prelamin A undergoes all of these reactions prior to removal of the antigenic peptide. Inhibitors of these reactions have been proposed as potential anticancer drugs, since they would be expected to block the biological activity of oncogenic p21ras proteins. Since such screening would be performed most efficiently by enzyme-linked immunosorbent assays, we can detect the accumulation of prelamin A after treatment with lovastatin by performing this procedure as well. Application of alpha-PA in an enzyme-linked immunosorbent assay, which demonstrates the activity of a peptidomimetic farnesyltransferase inhibitor, supports the use of this antibody in large scale screening for inhibitors of farnesylation-dependent protein processing. PMID- 8205545 TI - Preferential alternative splicing in cancer generates a K-sam messenger RNA with higher transforming activity. AB - K-sam, also designated fibroblast growth factor receptor 2/BEK, was originally cloned from a stomach cancer cell line KATO-III. The gene is amplified and overexpressed preferentially in poorly differentiated types of stomach cancers. The major K-sam transcript in KATO-III cells encodes a receptor protein with a truncated carboxyl terminus and with a high-affinity binding site for keratinocyte growth factor. This truncated type is produced by an alternative splicing mechanism, and in normal tissues, the truncated type is far less prevalent than the untruncated form. The variant K-sam complementary DNA lacks tyrosine 769, which is a putative phospholipase C gamma 1 association site, and showed a higher transforming activity to NIH3T3 cells than the untruncated form, which is identical with the keratinocyte growth factor receptor. PMID- 8205546 TI - Expression of interleukin 8 correlates with the metastatic potential of human melanoma cells in nude mice. AB - We correlated the steady state transcription and protein secretion of interleukin 8 (IL-8) in 13 different human melanoma cell lines with their ability to grow and produce metastasis in nude mice. Highly metastatic cells expressed higher steady state levels of IL-8 mRNA transcripts than did low metastatic cells. In situ mRNA hybridization analyses confirmed the pattern of mRNA expression on a cellular level. Increased mRNA expression directly correlated with secretion of IL-8 protein as determined by enzyme-linked immunosorbent assay. Recombinant IL-8 stimulated the proliferation of low metastatic A375P cells in a dose-dependent manner, a stimulation that was abrogated by the use of a polyclonal antibody against IL-8. The data suggest that IL-8 can be an autocrine growth factor for human melanoma cells and that IL-8 is involved in melanoma metastasis. PMID- 8205547 TI - Increased expression of DNA topoisomerase I gene and collateral sensitivity to camptothecin in human cisplatin-resistant bladder cancer cells. AB - We established three cis-diamminedichloroplatinum(II) (cisplatin)-resistant cell lines, T24/DDP5, T24/DDP7, and T24/DDP10, by the stepwise exposure of T24 human bladder cancer cells to increasing concentrations of cisplatin. The resistance to cisplatin of T24/DDP5, T24/DDP7, and T24/DDP10 cells was 2.2-, 5.2-, and 8.4-fold that of the parental T24 cells, respectively. The cisplatin-resistant cell lines also showed an increased resistance to vincristine, although their sensitivities to Adriamycin and etoposide resembled that of T24. In contrast, the cisplatin resistant cells developed a collateral sensitivity to (4s)-4,11-diethyl-4-hydroxy 9-[(4-piperidinopiperidino)carbonyl oxy]dione hydrochloride trithydrate, a camptothecin derivative, and its active metabolite, 7-ethyl-10-hydroxy camptothecin, that targets DNA topoisomerase I. Both a Northern blot analysis and an immunoblot analysis demonstrated increased cellular levels of DNA topoisomerase I mRNA in the resistant cell lines. However, the expression of DNA topoisomerase II in the three resistant cell lines did not differ significantly from that in the T24 cells. No significant differences in the glutathione S transferase pi levels were observed, although the intracellular content of glutathione in the T24/DDP7 cells was slightly but significantly increased. In addition, the intracellular platinum concentration correlated negatively with the degree of cisplatin resistance and was found to be significantly decreased in T24/DDP10 at an external cisplatin concentration of 20 micrograms/ml. These results suggest that the increased levels of DNA topoisomerase I mRNA thus play an important role in cisplatin resistance and produce a collateral sensitivity to (4s)-4,11-diethyl-4-hydroxy-9[(4-piperidinopiperidino)carbonylo xy]dione hydrochloride trithydrate and 7-ethyl-10-hydroxycamptothecin in these cisplatin resistant bladder cancer cell lines. In addition, the presence of decreased intracellular cisplatin accumulation may also contribute to the acquisition of resistance to cisplatin in these cell lines. PMID- 8205548 TI - Bcl-2 inhibits chemotherapy-induced apoptosis in neuroblastoma. AB - bcl-2 is the first member of a new class of protooncogenes the products of which inhibit programmed cell death (PCD) or apoptosis. We have previously determined that Bcl-2 is expressed in a significant percentage of untreated primary neuroblastoma (NBL) tumors. In these specimens Bcl-2 expression correlated with other markers of poor prognosis suggesting a role for Bcl-2 in the malignant behavior of NBL tumor cells. To investigate this possibility, a Bcl-2-negative human NBL cell line (Shep-1) was transfected with a bcl-2 expression vector (pSFFVneo-bcl-2). Multiple unique clones were isolated which showed variable levels of Bcl-2 protein by quantitative immunoprecipitation. Vector-transfected controls were generated simultaneously. Clones expressing high levels of Bcl-2 were resistant to cisplatin- and etoposide-induced cytotoxicity in a dose dependent manner. Analysis of propidium iodide-stained nuclei by flow cytometry after cisplatin or etoposide treatment revealed marked DNA degradation in vector transfected controls whereas bcl-2 transfectants showed a dose-dependent inhibition of DNA degradation. Analysis by pulsed-field gel electrophoresis revealed relatively large fragment DNA degradation (approximately 50 kilobases) in the absence of internucleosomal degradation in vector-transfected control cells treated with either cisplatin or etoposide. In contrast, Bcl-2-expressing cells showed significantly less DNA degradation at all time points. These single gene transfection experiments have revealed that expression of Bcl-2 renders specific NBL cells resistant to chemotherapy-induced PCD and support the hypothesis that Bcl-2 enhances the malignant phenotype of NBL by promoting tumor resistance to chemotherapy agents. PMID- 8205549 TI - Effects of antisense glial fibrillary acidic protein complementary DNA on the growth, invasion, and adhesion of human astrocytoma cells. AB - Glial fibrillary acidic protein (GFAP)-positive astrocytoma cells were stably transfected with an expression vector carrying a murine complementary DNA for GFAP in the antisense orientation. Three stably transfected GFAP-negative transformants were identified by indirect immunofluorescence and expanded in vitro. The stably transfected and control cell clones were analyzed for morphological alterations, growth in monolayer and soft agar, adhesiveness, and in vitro invasive potential. In contrast to control astrocytoma cells which retained an astrocytic phenotype with polygonal or triangular cells extending multiple long and thin processes, the antisense GFAP-transfected cells demonstrated marked morphological alterations in the form of flat, epithelioid cells devoid of long, astrocytic glial processes. The antisense GFAP-transfected clones demonstrated a greater degree of cell crowding and piling at confluence than did controls. By tritiated thymidine analysis, the antisense GFAP transfected cell clones demonstrated a 2-3-fold increase in incorporation of the radiolabel, suggesting an enhanced proliferative potential over controls. Antisense GFAP-transfected astrocytoma clones formed larger and more numerous colonies than did controls when tested for anchorage-independent growth in soft agar. Following a time-course adhesion assay, antisense GFAP-transfected astrocytoma clones were found to be less adherent to their substratum than controls. When assessed in an in vitro invasion assay system, antisense GFAP transfected astrocytoma cells more readily penetrated Matrigel-coated filters than did controls. These data have shown that eliminating GFAP expression from astrocytoma cells has affected astrocytoma cell morphology and adhesion. The data also suggest that the growth and invasive potential of the antisense GFAP transfected astrocytoma cells have been significantly enhanced by altering the expression of this glial-specific cytoskeletal protein in this experimental cell system. PMID- 8205550 TI - Characterization of five new cell lines derived from human primitive neuroectodermal tumors of the central nervous system. AB - Medulloblastoma (MB) represents the most frequent malignant brain tumor of childhood but only a few cell lines and animal models of this primitive neuroectodermal tumor (PNET) have thus far been established. Using specific cell culture conditions, we were able to derive four human MB cell lines (MHH-MED-1-4) as well as a cell line from a spinal PNET (MHH-PNET-5). The four MB cell lines grew in suspension as floating cell aggregates or as slightly adherent cells. They consisted of undifferentiated cells that did not express markers of late neuronal or glial lineages such as neurofilaments or glial fibrillary acidic protein. They also lacked expression of major histocompatibility complex class I or II antigens on the cell surface. All four MB lines were positive for vimentin and neuron-specific enolase, whereas synaptophysin, neural cell adhesion molecule, galactocerebroside, GD2, GD3, and the A2B5 antigen were expressed inconsistently. In contrast, MHH-PNET-5 grew as adherent monolayer and expressed major histocompatibility complex class I antigen. By cytogenetic analysis, the lines were near diploid with clonal aberrations. The MB lines showed no losses of chromosome arm 17p by either cytogenetic or microsatellite analyses. The cell line MHH-MED-2 exhibited double minute chromosomes, amplification of the c-myc gene, and overexpression of c-myc mRNA and protein. N-myc, p53, and Rb protein expression were unaltered. All four continuously passaged MB cell lines and the MHH-PNET-5 line were xenotransplanted s.c. into athymic mice; three of four MB lines and the spinal PNET line gave rise to tumors. These cell lines will be useful tools for biological and preclinical studies on PNETs. PMID- 8205551 TI - Potentiation by specific short-chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines. AB - The architecture of normal colonic mucosa suggest that terminally differentiated epithelial cells near the top of the crypt are extruded into the colonic lumen. Morphological studies have identified apoptotic cells among the differentiated phenotypes near the crypt-lumen interface, suggesting a link between pathways of differentiation, apoptosis, and cellular shedding. We studied these processes in HT29 and SW620 cells and found that compared to adherent cells, those cells which were shed during standard, uninduced culture conditions exhibited nonrandom DNA fragmentation characteristic of apoptosis. Moreover, these apoptotic cells, which accumulate in the media, exhibited a more differentiated phenotype. Because short chain fatty acids (SCFAs) are natural effectors of colonic cell differentiation in vivo, we investigated the specificity of three 4-carbon atom SCFAs on potentiating differentiation and apoptosis, and thus accumulation of shed cells in the conditioned media, in these colonic carcinoma cell lines. Whereas the unbranched SCFA butyrate induced a more differentiated phenotype and enhanced apoptosis, two derivatives of butyrate, branched isobutyric acid and a nonmetabolizable fluorine-substituted analogue, heptafluorobutyric acid, were ineffective in inducing either differentiation or apoptosis. Thus, potentiated differentiation and apoptosis in colonic carcinoma cells were linked to SCFA structure and, most likely, utilization. PMID- 8205552 TI - A dominated and resistant subpopulation causes regrowth after response to 1,3 bis(2-chloroethyl)-1-nitrosourea treatment of a heterogeneous small cell lung cancer xenograft in nude mice. AB - In order to address the question of the influence of a primarily chemoresistant tumor cell subpopulation on the progression of a heterogeneous tumor after cytotoxic therapy, in vitro established human small cell lung cancer cell lines of a 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-sensitive (592) and a resistant (NYH) tumor were used to produce mixed solid tumors in nude mice. Mixtures of 592/NYH (9:1 and 1:1) were inoculated s.c. After 3-4 weeks of tumor growth, the mice were stratified according to tumor size and randomized to treatment with BCNU 40 mg/kg i.p. (10% of lethal dose) or no treatment. Tumor growth curves were used to calculate the effect of the treatment, and changes in the relative proportions of 592 and NYH in the mixed tumors were monitored by flow cytometric DNA analysis by which the two cell lines were distinguishable due to differences in DNA content. A significant response was demonstrated in the 9:1 mixed tumors in which only 592 cells were detectable at the start of the treatment. The response was short and less pronounced compared with tumors containing only 592. In the regrowing tumors after treatment, only NYH was detected. In untreated 9:1 mixed control tumors, only 592 cells were detectable throughout the entire observation period. It is substantiated that the 592 cells were able to inhibit the growth of the NYH cells completely when grown together in 9:1 mixed tumors. This was not the case in the 1:1 mixed tumors. The 1:1 mixed tumors did not respond to BCNU, although 592 was eradicated. These results indicate that resistant and undetectable (dominated) subpopulations in heterogeneous tumors may be responsible for relapse and that the fractional size and the growth characteristics of the resistant subpopulation may determine the magnitude of the clinical response to cytotoxic treatment. PMID- 8205553 TI - Enhancement of the expression of urokinase-type plasminogen activator from PC-3 human prostate cancer cells by thrombin. AB - The presence of procoagulants and fibrin deposition have been demonstrated in malignant tumors. Although thrombin, a key enzyme in coagulation, has other various biological functions, the significance of its presence in tumors is not known. We studied the effects of thrombin on the expression of urokinase-type plasminogen activator (uPA) which is known to play a role in tumor invasion, using a human prostate cancer cell line PC-3. Human alpha-thrombin added to cultures of PC-3 produced a dose-dependent and time-dependent increased secretion of uPA that was greatest at 3-6 h after exposure to thrombin. Increase in uPA antigen paralleled the increase in mRNA level, which reached a maximum at 4 h. Thrombin showed the maximum effect on uPA expression at a concentration 1-2 units/ml. Zymography showed that transient exposure to thrombin induced an increase in fibrinolytic activity which could be quenched by anti-uPA antibody. The thrombin receptor-activating peptide also caused an increase in uPA protein and mRNA level, indicating the presence of the same thrombin specific receptor on PC-3 cells as on platelets and endothelial cells. Thrombin did not affect the expression of other components of the plasminogen activation system, tissue-type plasminogen activator and type-1 plasminogen activator inhibitor, and uPA receptor. These results indicate that thrombin increases uPA expression selectively by the stimulation of a functional thrombin receptor on PC-3 cells. Since uPA is known to play a role in pericellular proteolysis of extracellular matrix, thrombin may be involved in the regulation of tumor invasion and metastasis. PMID- 8205554 TI - Expression of carcinoembryonic antigen and nonspecific cross-reacting 50-kDa antigen in human normal and cancerous colon mucosa: comparative ultrastructural study with monoclonal antibodies. AB - The precise localization of carcinoembryonic antigen (CEA) and non-specific cross reacting 50-kDa antigen (NCA 50) in normal colon mucosa and colon adenocarcinoma was investigated by using an indirect immunoperoxidase electron microscopic technique with specific monoclonal antibodies. In normal adult colon both antigens were localized to microvesicles and filaments of the "fuzzy coat" on the apical surface of the epithelial cells. In addition, NCA 50 was found in the narrow spaces between adjoining microvilli. Mature columnar cells at the free luminal surface contained most of the antigen positive material. CEA and NCA 50 were also detected as intracellular components of goblet cells. In multilayered tumor glands, the cell surface expression of the antigens was dependent on the position of the tumor cell in the gland. The neoplastic cells showed either a predominant apical labeling or a positive staining of almost the entire cell surface. Some of the neoplastic cells contained CEA in so-called "intracellular lumina." In contrast to normal colon epithelial cells most tumor cells synthesized NCA 50 actively. In normal colonic mucosa, unlike in cancerous tissue, CEA and NCA 50 appear to be released via vesicles formed from the microvillous membrane of mature columnar cells. These results are consistent with the hypothesis that CEA and NCA play a role in the nonspecific defense against microorganisms in the large intestine. PMID- 8205555 TI - Correspondence re: S.E. Dew et al., Effects of pharmacological retinoids on several vitamin A-metabolizing enzymes. Cancer Res., 53: 2965-2969, 1993. PMID- 8205556 TI - The role of major histocompatibility complex expression on head and neck cancer cells in the induction of autologous cytotoxic T lymphocytes. AB - Using head and neck tumors, we studied the role of HLA class I and DR antigens on tumor cells in cytotoxic T lymphocyte (CTL) induction. Expression of major histocompatibility complex (MHC) antigens was investigated by two-color flow cytometry analysis and for this study we used the tumor cells, over 50% of which expressed both HLA class I and DR antigens on their surface. In seven cases, tumor cells were divided into three groups according to the specificity of monoclonal antibodies (mAb) to MHC to study the role of MHC antigens on tumor cells in CTL induction: one was not blocked (MHC double-positive tumor), a second was blocked by anti-class I mAb (class-I-negative DR-positive tumor) and third was blocked by anti-DR mAb (class-I-positive DR-negative tumor). Subsequently, these tumors were used to stimulate an autologous mixed lymphocyte/tumor cell culture for 5 days (MLTC) followed by further cultivation with interleukin-2 for 12 days. The induced autologous tumor killer cells were most cytotoxic when non treated tumors, which consist mainly of cells that are both HLA-class I and DR positive, were used as stimulator cells. When the tumor cells blocked by anti-DR mAb were used as stimulators, autologous tumor killer activity was lower than that induced by tumor cells blocked by anti-class-I mAb. Moreover, cytolysis by autologous tumor killer cells induced by stimulation of non-treated tumor cells was blocked during the effector phase, 26.6%-42.3% and 32.7%-53.8% by anti-class I and anti-DR mAb respectively, suggesting that majority of the autologous tumor killer cells are MHC-restricted CD8+ or CD4+ CTL. These results suggest that both MHC class I and class II antigens on head and neck tumor cells play a critical role in inducing CTL. PMID- 8205557 TI - Bacillus Calmette-Guerin potentiates monocyte responses to lipopolysaccharide induced tumor necrosis factor and interleukin-1, but not interleukin-6 in bladder cancer patients. AB - During the past decade, particular attention has been focused on treatment of bladder cancer patients with the bacterial agent bacillus Calmette-Guerin (BCG). In these studies, bladder cancer patients were instilled with BCG (75 mg/50 ml) once per week for 6 weeks, 1-2 weeks following trans-urethral resection of the bladder. Cystoscopy was performed after 6 weeks and, unless tumor progression was present, monthly treatments were given for 1 year. Blood was drawn 2 h after the last instillation, and monocytes were isolated (5 x 10(6) cells/ml) and treated, or not, with lipopolysaccharide (LPS) (20 microgram/ml) for tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha) and interleukin-6 (IL-6) release. The levels of monokines were determined by a monokine-specific enzyme linked immunosorbent assay. Our results clearly show that, after 18 h incubation, macrophages from BCG-treated bladder cancer patients produced from 2.8- to 1.9 fold and from 2.0- to 1.3-fold greater amounts of TNF alpha and IL-1 alpha respectively, compared to macrophages from healthy controls, 5-fold higher than bladder cancer patients not treated with BCG. IL-6 was not affected. In another set of experiments macrophages (5 x 10(6) cells/ml) from healthy subjects were pretreated, or not, with BCG (100 micrograms/ml) overnight and treated, or not, with LPS 20 microgram/ml alone and in combination with interleukin-1 receptor antagonist (IL-1ra) 250 ng/ml. Macrophages treated with BCG had a strong stimulatory effect on IL-1 alpha release (9.45 ng/ml) while LPS was less effective (3.59 ng/ml). The combination of BCG plus LPS produced an additive effect on IL-1 alpha release (13.71 ng/ml) compared to the effect of the compound alone. The addition of IL-1ra (250 ng/ml) to BCG was not effective, while when IL 1ra was added to BCG plus LPS only a partial inhibition of IL-1 alpha release was found (9.83 ng/ml), compared to BCG plus LPS without IL-1ra (13.71 ng/ml). These effects seem to be related to the inhibition of IL-1 alpha stimulated with LPS, but not BCG. The priming effect of BCG exerted on LPS-stimulated monocyte production of TNF alpha and IL-1 alpha from bladder cancer patients led us to study the possible modulation of fibrinogen and C-reactive protein in the serum of BCG-treated cancer patients. The plasma levels of fibrinogen and C-reactive protein were higher (approximately twice) in BCG-treated patients compared to values obtained in untreated patients or healthy controls. We conclude that the beneficial immunotherapeutic effects of BCG in bladder cancer patients are related to its capacity to prime macrophages to enhance the release of TNF alpha and IL-1 alpha, but not IL-6 in response to physiological secondary stimuli, or through the direct stimulation of BCG on IL-1 alpha or TNF alpha, which are directly involved in the killing of cancer cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8205558 TI - Immunological characterization of tumor-rejection antigens on ultraviolet-light induced tumors originating in the CB6F1 mouse. AB - Six ultraviolet-light(UV)-induced tumors of (BALB/c x C57BL/6)F1 (H-2d/b) mouse origin were analyzed for the effector T cell subsets involved in tumor rejection, the MHC class I to which cytolytic T lymphocytes (CTL) are restricted, and the effect of UV radiation on tumor rejection, to characterize their tumor-rejection antigens (TRA) recognized by CTL. All tumors were rejected in syngeneic normal mice but grew progressively in nude mice. CD8+ T cells mediated the antitumor responses for all tumors and CD4+ T cells could also do so for one tumor 6.1B. Each tumor induced potent CTL that recognized the specific TRA in preferential association with MHC class I haplotypes not from H-2b but from H-2d; that is, Kd, Dd or Ld. Profiles of TRA expression on two tumors were obtained by the analyses of their antigen-loss variants. Female 1A codominantly expressed at least four distinct TRA associated with Kd, all of which induced CTL. On the other hand, UV male 1 had at least two distinct TRA, one of which, associated with Kd, exclusively induced CTL. However, in the absence of the dominant TRA, another TRA associated with Ld on R95C, a variant of UV male, 1, induced CTL. Unlike other tumors, R95C grew progressively in short-term-UV-irradiated syngeneic mice. Nude mice reconstituted with a combination of CD4+ T cells from short-term-UV irradiated mice and CD8+ T cells from normal mice did not reject R95C. An increase in the former T cell population led the reconstituted mice to reject the tumor. These findings suggest some functional defects of CD4+ T cells rather than the generation of suppressor cells in short-term-UV-irradiated mice. The UV induced tumors used in the present study provide a unique system for analyzing the preferential sorting of TRA as well as for elucidation of the TRA itself. PMID- 8205559 TI - A phase II study of combined administration of dacarbazine and carboplatin with home therapy of recombinant interleukin-2 and interferon-alpha 2a in patients with advanced malignant melanoma. AB - Chemotherapy and interleukin-2 (IL-2) and/or interferon alpha (IFN alpha) produce objective responses in a proportion of patients with advanced malignant melanoma. The duration of response to chemotherapy is usually less than 4 months, and immunotherapy has resulted in long-lasting remissions in a small number of patients with metastatic melanoma. The current study was conducted to improve the antitumor efficacy and the interactions between recombinant (r) IL-2, rIFN alpha 2a and chemotherapy. A total of 16 evaluable patients with metastatic malignant melanoma were entered into a phase-II study designed to assess the response rate and therapeutic efficacy of dacarbazine and carboplatin followed by rIL-2 and rIFN alpha 2a. Patients received 750 mg/m2 dacarbazine with 400 mg/m2 carboplatin each by intravenous bolus on days 1 and 22. Recombinant IL-2 and IFN alpha 2a were administered on an outpatient basis (home therapy) subcutaneously for 6 consecutive weeks: 4.8 x 10(6) IU/m2 rIL-2 daily, 5 days a week; 6.0 x 10(6) IU/m2 rIFN alpha 2a thrice weekly. There were responses in 6 of the 16 enrolled patients with an overall response rate of 37.5% (95% confidence interval: 14% 61%). All responding patients had partial responses. The median survival time of the responding patients was significantly better than that of patients with progressive and stable disease (P = 0.03). The median duration of response was 11 months (range 2-24 months). Responses in lung, liver, soft tissue and lymph-node sites were noted. PMID- 8205560 TI - T cell recognition of melanoma antigens in association with HLA-A1 on allogeneic melanoma cells. AB - Previous studies have shown that recognition of melanoma by cytotoxic T lymphocytes may be restricted by HLA-A1, A2 and other HLA antigens. The present study examined the cytotoxic specificity and major histocompatibility complex restriction of cloned cytotoxic T lymphocytes (CTL) isolated from a patient with the HLA phenotype A3,31 who had been immunized with a vaccine prepared from HLA A1,3 melanoma cells. Cytotoxic assays against HLA-typed allogeneic melanoma cells indicated that cloned CTL from the patient were able to kill allogeneic melanoma cells expressing HLA-A1 but not other HLA-A1-positive cells. Studies on a representative clone indicated that proliferation and cytokine (tumour necrosis factor alpha) production in response to melanoma cells was also associated with HLA-A1 on melanoma cells. Response to the melanoma cells was associated with interleukin-4 (IL-4) rather than IL-2 production. The antigen recognized in the context of HLA-A1 on allogeneic melanoma cells was detected in cytotoxic assays on cells from 9 of 12 HLA-A1+ melanoma cell lines and did not appear to be the product of the MAGE-1 or -3 genes. These findings suggest that T cells can recognize melanoma antigens in the context of alloantigens and that allogeneic vaccines containing "immunodominant" alloantigens may generate CTL that are ineffective against autologous melanoma. The study does not, however, exclude the possibility that CTL with specificity to the latter may be activated by allogeneic vaccines, and further studies are needed to answer this question. PMID- 8205561 TI - Non-fastidious, melanoma-specific CD8+ cytotoxic T lymphocytes from choroidal melanoma patients. AB - To characterize the anti-melanoma reactivity of CD8+ cytotoxic T lymphocytes (CTL) from choroidal melanoma patients, CTL clones were isolated from the peripheral blood of three patients after mixed lymphocyte/tumor cell culture (MLTC). Clones were derived from lymphocytes stimulated by allogeneic (OCM-1, A24, A28) or autologous (OCM-3, A1, A30) melanoma cells. Their reactivity against a panel of HLA-typed melanoma and nonmelanoma cells was assessed, to determine whether a single CTL clone could recognize and lyse a variety of allogeneic melanoma cell lines. While proportionately more clones derived from autologous MLTC were melanoma-specific than allogeneic MLTC (42% versus 14%), melanoma specific CTL were recovered from both. Notably, a novel melanoma specificity was identified. These CTL clones were termed non-fastidious because they were capable of lysing melanoma cells with which they had no HLA class I alleles in common. Nonetheless, lysis was mediated by the HLA class I molecule. Since lysis was specific for melanoma cells, these CTL appeared to recognize a shared melanoma peptide(s). Because of their prevalence, we propose that non-fastidious CTL are integral to human anti-melanoma T cell immunity. This reinforces clinical findings that allogeneic melanomas can substitute for autologous tumors in active specific immunotherapy. By circumventing the need for autologous melanoma, it is possible to treat patients after removal of the primary choroidal melanoma in an attempt to prevent metastasis. PMID- 8205562 TI - Interferon beta enhances the natural killer activity of patients with bladder carcinoma. AB - We have investigated the effect of interferon beta (INF beta) on the natural killer (NK) cytotoxic activity of peripheral blood mononuclear cells (PBMC) from patients with superficial and infiltrative transitional-cell carcinoma of the bladder (TCC) against both NK-sensitive and NK-resistant target cells. The normal NK activity found in PBMC from these patients can be significantly enhanced by short-term incubation (18 h) with INF beta (P < 0.05). The depressed NK cytotoxic activity found in PBMC from patients with infiltrative TCC can also be significantly enhanced, but not normalized, by short-term incubation with INF beta (P < 0.05). In kinetic studies we found that the maximal levels of the INF beta-promoted cytotoxic activity against NK-sensitive and against NK-resistant target cells in PBMC from TCC patients were reached after 18 h of culture. Short term-INF beta-incubated PBMC from patients with TCC of the bladder also showed marked cytotoxic activity against NK-resistant target cells. The effector cells of the INF beta-induced cytotoxic activity in PBMC from patients with TCC were CD16+ CD3- NK cells. This cytotoxic inducer effect of INF beta synergized with that of interleukin-2. In conclusion, INF beta can enhance the NK activity of PMBC from patients with TCC of the bladder. PMID- 8205563 TI - Vitiligo- and melanoma-associated hypopigmentation: a similar appearance but a different mechanism. AB - The significance of the association between the appearance of hypopigmentation in patients with melanoma and the prognosis is still not clear. It was postulated that, in melanoma, an immune response is responsible for the destruction of the malignant as well as the normal pigmented cells, and that the eventual development of vitiligo-like patches in melanoma patients improves their prognosis. We studied the level of anti-melanoma antibodies in the sera of patients with melanoma with hypopigmentation and compared it to the titer in patients with melanoma only, to the titer of patients with vitiligo, and to that of healthy subjects. Only IgG-type antibodies were found in the sera of patients with vitiligo, with melanoma, or with melanoma with hypopigmentation. No significant differences in the titer of anti-melanoma antibodies could be found between the patients with melanoma when subgrouped according to the initial stage and the status of the disease at the time when the test was carried out. Statistically significantly (P < 0.001) higher titers of antibodies were detected in the sera of patients with vitiligo in comparison to the lower titers in the other groups. Our results point to a similar immunobiological status, which probably does not give any advantage to patients with melanoma with hypopigmentation compared to patients without it. The appearance of hypopigmentary plaques in melanoma patients should be regarded, in our opinion, as a concomitant immunological phenomenon of the disease. PMID- 8205564 TI - Circulatory support devices in clinical cardiology. Current concepts. AB - Percutaneous transluminal coronary angioplasty (PTCA) has extended its indications to multivessel disease and impaired left-ventricular function. In these patients, failed PTCA may induce cardiogenic shock or arrest. Coronary and circulatory support devices such as antegrade perfusion catheters, coronary sinus retrograde perfusion, intraaortic balloon pumping, left-ventricular pumping (Hemopump) and percutaneously applicable cardiopulmonary support are the tools necessary for high-risk PTCAs. The devices are a prerequisite for developing a minimally invasive cardiac surgery. PMID- 8205565 TI - Counterpulsation: historical background, technical improvements, hemodynamic and metabolic effects. AB - The intraaortic balloon counterpulsation is performed today on the same principles that were described in its first experimental use in 1962. Experimental studies have shown significant increase of the mean aortic diastolic pressure, the diastolic pressure-time index, endocardial viability ratio, cardiac output, ejection fraction, coronary cerebral and renal blood flow, lactate utilization and myocardial oxygen supply and significant decrease of the systolic aortic pressure, left-ventricular end-diastolic pressure, left-ventricular work, tension time index, myocardial oxygen consumption and lactate production. In similar studies, intraaortic balloon pump (IABP) decreases the size of myocardial infarction. New IABP driving systems, small size sheaths and balloon catheters for percutaneous insertion made the use of the IABP easier and safer. The paraaortic counterpulsation device is suitable for chronic mechanical assistance. It is more effective than the IABP and shows excellent biocompatibility in chronic experiments. Its clinical application in 3 patients showed excellent biocompatibility and promising hemodynamic effects. In conclusion, the salutary hemodynamic effects of the IABP have been shown in several experimental studies. The technical improvements and the development and use of new devices suggest that we still need to learn more about the usefulness of the counterpulsation technique. PMID- 8205566 TI - Role of intra-aortic counterpulsation in cardiogenic shock and acute myocardial infarction. AB - IACP has played an important role in the evolution of the therapy of cardiogenic shock. Although IACP has not developed to an independent treatment modality, it is an essential adjunct to facilitate early catheterization and reperfusion strategies. With this combined approach, hospital and long-term survival rates have reached encouraging results. In acute myocardial infarction, IACP may evolve into an intriguing adjunct to thrombolysis and/or PTCA. Preliminary data suggest that IACP might decrease the rate of reocclusion and reinfarction after thrombolysis and/or PTCA and, thus, interrupt the vicious cycle of infarct extension, development of left-ventricular failure and cardiogenic shock. Further research is in progress. PMID- 8205568 TI - Technical requirements and limitations of miniaturized axial flow pumps for circulatory support. AB - The engineering principles of rotary blood pumps are elucidated by means of a basic introduction into turbomachinery. Additionally, some important dimensionless quantities which relate to pumping characteristics and pump type are introduced. These theoretical fundamentals are applied to the design of high speed microaxial pumps, especially the two Hemopump versions. The theoretical estimates clearly show that each pump version has its physical limits, especially at small impeller sizes. It is also demonstrated that not any clinically desirable working point of an axial pump can be achieved with an arbitrarily small pump size. PMID- 8205567 TI - Intraaortic balloon pump support during high-risk coronary angioplasty. AB - Intraaortic balloon pump support has been demonstrated to be of clinical benefit when used therapeutically and prophylactically in high-risk patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Afterload reduction and post-PTCA-enhanced coronary blood flow afforded by diastolic augmentation during intraaortic balloon pumping provides hemodynamic stabilization, attenuates clinical perturbations of myocardial ischemia, and may provide an important 'bridge' to emergent coronary bypass surgery following abrupt vessel closure complicating PTCA. Recent studies demonstrate a reduction in cardiac morbidity and improved coronary artery patency among patients receiving prophylactic intraaortic balloon pumping after establishing infarct artery reperfusion during acute cardiac catheterization for acute myocardial infarction. A modest increase in cardiac output (20-30%), the requirement of a stable, regular cardiac rhythm, peripheral vascular disease and aortic insufficiency limits the use of intraaortic balloon pump support in relatively few patients. These studies demonstrate that intraaortic balloon counterpulsation provides an effective and safe form of mechanical support in many high-risk patients undergoing PTCA. PMID- 8205569 TI - Circulatory support of cardiac interventional procedures with the Hemopump cardiac assist system. AB - The Hemopump is a catheter-mounted mechanical circulatory assist device which can support the majority of the circulation and significantly reduce left-ventricular work. It can be introduced via a peripheral artery or the ascending aorta. The following is an overview of the operation of the Hemopump and the results of a clinical trial in which the Hemopump was used to treat cardiogenic shock. In addition, the results of pilot experiences using the Hemopump for circulatory support during aorto-coronary artery surgery and high-risk angioplasty will be discussed. PMID- 8205570 TI - Left-ventricular unloading by transvalvular axial flow pumping in experimental cardiogenic shock and during regional myocardial ischemia. AB - The efficacy of the transfemoral left-ventricular assist device Hemopump (HP; 21 Fr outer diameter) was examined in experiments with adult sheep in two different models of cardiogenic shock (tachycardia shock; ischemia shock), and during ventricular fibrillation. During tachycardia (high frequency pacing-induced; n = 14), HP assist led to a significant increase in cardiac output (from 2.2 to 2.8 liters/min), mean aortic pressure (from 47.6 to 65.6 mmHg), and myocardial perfusion pressure (from 25.5 to 59.0 mmHg). Simultaneously, a normalization of body oxygen-uptake (from 1.4 to 2.5 ml/min.kg), a decrease in myocardial oxygen consumption (from 6.1 to 4.8 ml/min.100 g), and a normalization of myocardial lactate metabolism were observed during HP assist. During regional myocardial ischemia (PTCA balloon occlusion of the proximal LAD (3.5 min; n = 12), HP assist led to significant decrease in LV end-diastolic pressure (from 21.1 to 12.1 mmHg), and increase in diastolic aortic pressure (from 58 to 67 mmHg) resulting in significant increase in coronary perfusion pressure. In the early reperfusion period, myocardial release of both lactate and potassium was significantly lowered with HP assist. During ventricular fibrillation (induced by electrical stimulation; n = 9), HP flow rates decreased from 2.5 (after 10 min) to 2.1 liters/min (after 30 min). Mean aortic pressures simultaneously decreased from 64.0 to 54.6 mmHg. Perfusion conditions were sufficient for maintenance of aerobic myocardial metabolism, but were borderline for peripheral circulation. Our hemodynamic and metabolic data demonstrate beneficial effects of cardiac assist with the Hemopump 21 Fr in both tachycardia-induced severe cardiogenic shock and during acute regional myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205571 TI - Use of left-ventricular assist with the Hemopump in cardiac surgery. AB - From July 1989 to May 1992 16 patients received circulatory support with a Hemopump assist device in the Department of Cardiac Surgery of the Katholieke Universiteit Leuven. The mean age of those patients was 56 +/- 13 years (ranging from 23 to 72 years). The mean time of assisted circulation was 60 +/- 46 h (ranging from 2 to 168 h). Group I consists of 13 patients who received the device after postcardiotomy cardiac failure (survival 38%). Group II includes 1 patient who received the pump prior to repair of a large postinfarction ventricular septal defect (survival 10%). Group III consists of 2 patients for whom the Hemopump was used as a bridge to cardiac retransplantation. Both are still alive (survival 100%). If the 21-F Hemopump is implanted following a critical indication it can be used rather successfully for mechanical circulatory support. PMID- 8205572 TI - Percutaneous cardiopulmonary support (PCPS). AB - The cardiopulmonary support system allows to maintain the patient's cardiac and pulmonary functions when the patient's cardiac or pulmonary status is failing. This system consists of a centrifugal pump with its control system, membrane oxygenator, measure devices for blood flow and pressure and a heating system for temperature conditioning of blood. The percutaneous application is easy and fast. Rapid priming, rapid insertion and high flow rates are characteristic for this method. The material costs for cardiac support of one patient are high, the price for one patient amounts to approximately DM 3,500. For the application the presence of an operating cardiologist, an anesthetist and a perfusionist is necessary. PMID- 8205573 TI - Need for active left-ventricular decompression during percutaneous cardiopulmonary support in cardiac arrest. AB - During ventricular fibrillation, myocardial hemodynamic and metabolic effects of percutaneous cardiopulmonary support (PCPS) were analyzed in 11 adult sheep (body weight 77-112 kg). During supported fibrillation, an abrupt increase in left ventricular pressures with alignment to aortic pressures was observed in 2 animals, which was probably due to spontaneous aortic regurgitation, and resulted in deterioration of coronary perfusion. In 9 animals, left-ventricular pressures rose from 22.9 +/- 4.9 to 31.2 +/- 7.9 mm Hg elevating left ventricular wall stress from 16,750 +/- 8,745 to 28,835 +/- 8,892 dyn/cm2 after 10 min of PCPS supported fibrillation (mean flow rate 4.5 +/- 0.7 liters/min). Simultaneously, myocardial perfusion pressures decreased from an average of 32.4 +/- 11.7 to 22.3 +/- 9.4 mm Hg and myocardial lactate release was observed. Additional transapical LV venting using a 9-Fr catheter led to a decrease in both LV pressure (to 25.7 +/- 5.3 mm Hg) and wall stress (to 20,612 +/- 7,499 dyn/cm2). Left-ventricular decompression decreased myocardial oxygen consumption (from 5.3 +/- 1.4 to 4.8 +/ 0.9 ml/min.100 g), and reduced myocardial lactate release, which indicates myocardial protection. Protective effects were most pronounced using 12-Fr-, and 21-Fr-venting cannulas (with 21 Fr: decrease in myocardial oxygen consumption to 2.7 +/- 0.6 ml/min.100 g, and reversal of myocardial lactate release to lactate uptake during fibrillation). Conclusions. Hemodynamic and metabolic data clearly demonstrate the deleterious effects of PCPS to the unvented left ventricle during cardiac arrest. The results emphasize the need for active left-ventricular decompression during PCPS in ventricular fibrillation. PMID- 8205574 TI - Emergency cardiopulmonary support with circulatory support devices. AB - Emergency cardiopulmonary support has been used in the United States since 1986, mainly by physicians at participating centers for the National Registry of Elective Supported Angioplasty. Data from the National Registry as well as the experience in three institutions from a number of operators were analyzed to assess the benefits of the emergency cardiopulmonary support application in patients with hemodynamic collapse. Patients who had experienced either cardiac arrest or hemodynamic collapse with cardiogenic shock unresponsive to pressors were placed emergently on cardiopulmonary support. They were either then treated with angioplasty or with revascularization surgery. Patients placed on cardiopulmonary support in less than 15 min experienced a 48% survival rate across the whole registry of the participating centers of the National Cardiopulmonary Bypass Registry. A two-center experience has demonstrated a 69% survival rate. Patients treated with emergency cardiopulmonary support who have experienced hemodynamic collapse have improved survivorship over any other hemodynamic support system. With increasing experience by the operators, the results have improved for survivorship, particularly in the early application group. PMID- 8205575 TI - National Registry for Supported Angioplasty: results and follow-up of three years of supported and standby supported angioplasty in high-risk patients. AB - The National Registry of Supported Angioplasty was formed in 1988 to collect data on patients undergoing supported angioplasty. The Registry was expanded to include patients also undergoing standby supported angioplasty. In 3 years the Registry collected data on 801 patients undergoing supported or standby supported angioplasty. The data indicate that in patients with low ejection fractions and/or > or = 50% of jeopardized myocardium at risk can have an interventional procedure performed with a 6.9% risk of mortality with prophylactic or standby support, but patients with < or = 20% ejection fraction do better with prophylactic support. In addition, patients with LMCA stenosis and age > or = 70 years are at higher risk. The Registry also demonstrates good long-term results for patients who have undergone the procedure. PMID- 8205576 TI - Considerations and variations of dentist-prescribed, home-applied vital tooth bleaching techniques. AB - Tooth-bleaching procedures became widely available with the 1989 introduction of a dentist-home technique. Over-the-counter home systems were put on the market shortly thereafter, but safety concerns led to a sales ban by the Food and Drug Administration (FDA) in 1991. That ban has been lifted while companies continue to supply information to the FDA. Information on bleaching safety has often been skewed because the high 35% hydrogen peroxide concentration used in the dentist office procedures has sometimes been compared out of context with dentist-home formulas with 10% to 15% carbamide peroxide or 1% to 10% hydrogen peroxide. Earlier studies have also failed to put the risk level of tooth bleaching into perspective with other routine dental procedures. More recent studies show that 10% carbamide peroxide is safe when appropriately administered. Haywood does state that there is a risk level in any type of bleaching, and that the dentist home system provides the best way to minimize the risk because the dentist can: (1) diagnose any problems or special needs; (2) plan appropriate treatment; and (3) fabricate, fit, and adjust the prosthesis used to apply the formula. A success rate of 96% (excluding tetracycline stain) has been achieved. Currently, most marketed systems use a carbamide peroxide in a thickened glycerin base. A new product is being introduced with 10% carbamide peroxide, a peroxide stabilizer, a thickener, and tooth-cleansing technology ingredients. PMID- 8205577 TI - Safety profile of Colgate Platinum Professional Toothwhitening System. AB - Colgate Platinum, a professional tooth-whitening paste containing 10% urea peroxide as the active ingredient, was evaluated for potential acute oral toxicity, genotoxicity, and irritation to oral mucosa. Oral administration to rats of a single dose of 5 g/kg of Colgate Platinum did not induce any adverse effects. Colgate Platinum was not mutagenic in Ames/Salmonella Plate Incorporation assay and did not induce primary DNA damage in the bone marrow hematopoietic cells of rats that were given oral doses of up to 1 g/kg for 5 consecutive days. Results of the oral mucosa irritation study in rats indicated that Colgate Platinum did not induce damage to soft and hard tissues of oral cavity after repeated applications for 28 days. Collectively, the data from these studies document the safety of the product for the intended use. PMID- 8205578 TI - Effects of Colgate Platinum Professional Toothwhitening System on microhardness of enamel, dentin, and composite resins. AB - The purpose of this study was to evaluate the effect of Colgate Platinum Professional Toothwhitening System on the microhardness of enamel, dentin, and two composite resins. This in vitro study replicated conditions in the oral cavity and followed the prescribed procedure for whitening teeth. The results of this study showed no significant differences in the microhardness of the control and treated teeth or the composite restorations tested. This indicates that the use of Colgate Platinum will not soften teeth or the composite restoratives studied. PMID- 8205579 TI - Development of a quantitative measurement to assess the whitening effects of two different oxygenating agents on teeth in vivo. AB - A new approach to assess color change in teeth involves application of the Minolta CR-221 Chroma Meter. The process has been assessed in vitro by Dr. Stephen Rosenstiel of Ohio University and by Dr. Robert Seghi of the University of California School of Dentistry. The purpose of this study was to develop a technique to assess the tooth-whitening effects of peroxides on teeth in vivo, using a small-area colorimeter. Twenty male and female subjects participated. Study casts were made from alginate impressions. Two maxillary, white, polyvinyl siloxane, custom-postioning splints were fabricated for each subject. Each splint was modified to accept exactly the head of the colorimeter to a window exposing the middle one third of the facial surface of one central incisor. The coloimeter converts all colors within the range of human perception into a common numerical code. The use of the positioning splint allowed the researchers to reposition the colorimeter precisely for multiple reading each time measuremehts were taken. The color parameters were recorded in the L*a*b* color space. This method shows that multiple measurements on the same subject are consistent and statistically accurate. The standard deviation for L* (lightness) values was 0.22. This technique showed quantitatively the whitening effect on teeth to be increase in L* and a decrease in a* (red) and b* (yellow). The mean color difference (deltaE) for the 3-week study was 5.07. PMID- 8205580 TI - Comparative clinical evaluation of two professional tooth-whitening products. AB - A 2-week study was conducted to compare the tooth-whitening efficacy of two 10% carbamide peroxide products: Colgate Platinum Professional Toothwhitening System and Rembrandt Lighten Bleaching Gel. Fifty subjects were divided into two groups and assigned a product to use for 2 weeks. Change in tooth color was measured by reflectance spectroscopy at the initiation of study, at 1 week, and at 2 weeks into the study. Color change was calculated using the color-difference equation established by the Commission International de L'Eclairage. Results showed that Colgate Platinum was 62% more effective at tooth whitening after 1 week and 83% more effective after 2 weeks of treatment vs Rembrandt. At the termination of the study, the mean color difference (deltaE) for Colgate Platinum was 4.29 and 2.34 for Rembrandt. Statistical analysis demonstrated that the Colgate product is significantly superior at increasing tooth whiteness, increasing tooth lightness, reducing redness, and reducing yellowness. In this study, no adverse reactions were noted on clinical examination and none were reported by panelists with normal healthy dentition. PMID- 8205581 TI - Clinical evaluation of Colgate Platinum Professional Toothwhitening System and Rembrandt Lighten Bleaching Gel. AB - A 2-week study was conducted to evaluate the tooth-whitening efficacy of Colgate Platinum Professional Toothwhitening System vs Rembrandt Lighten Bleaching Gel. Thirty-eight subjects completed this single-blind, randomized, parallel clinical study. The subjects were balanced into two groups based on a minimal shade of A3 on the Vita shade guide. The duration of product use was 30 minutes, twice daily for 2 weeks. Change in toodth color was measured by reflectance spectroscopy using a colorimeter. The readings were taken in the L*, a*, and b* color space at the initiation of the study, at 1 week, and at 2 weeks. Calculation of color change (deltaE) was performed using the color difference equation established by the Commission International de L'Eclairage. Results demonstated that Colgate Platinum was 46% more effective at tooth whitening after 1 week, and 96% more effective after 2 weeks of treatment. The results demonstrated that the Colgate product was significantly superior vs Rembrandt at increasing tooth whiteness (increase in deltaE), and tooth lightness (increase in deltaL*). No adverse reations were noted on clinical examination. PMID- 8205582 TI - Clinical comparison of Colgate Platinum Toothwhitening System and Rembrandt Gel Plus. AB - A 2-week, three-cell study was conducted to evaluate the tooth-whitening efficacy of the Colgate Platinum Professional Toothwhitening System vs Rembrandt Gel Plus (a regimen of products consisting of a 10% carbamide peroxide gel, a whitening toothpaste, and a mouthrinse), and a placebo paste. Seventy subjects completed this parallel, single-blind, three-compartment, randomized clinical study. The subjects were balanced into two groups based on a minimal shade of A3 on the Vita shade guide and assigned a product. The duration of product usage was 1 hour twice daily for 2 weeks. Change in tooth color was measured by reflectance spectroscopy using a colorimeter. The readings were taken in the L*, a*, b* color space at the initiation, at 1 week, and at 2 weeks of the study. Calculation of color change (delta E) was performed using the color difference equation established by the Commission Internationale de L'Eclairage. Visual evaluation of shade changes was performed using the Vita shade guide. Results from this clinical study showed that Colgate Platinum was 77.7% more effective at tooth whitening after 1 week and 41.8% more effective after 2 weeks of treatment vs the Rembrandt regimen. Results showed that the Colgate product is significantly superior vs Rembrandt at increasing tooth whiteness (increase in delta E). Shade guide changes showed an overall improvement of 7.08 Vita tabs for the Colgate product and 5.12 Vita tabs for the Rembrandt regimen. PMID- 8205583 TI - Restoration of esthetic areas using nonsubmerged dental implants. PMID- 8205584 TI - Full veneers: the functional and esthetic application of bonded ceramics. AB - Esthetic restorative practices have used bonded ceramic facial veneers to replace or augment defective, discolored, or missing enamel. These restorations have proved to be highly esthetic and extremely durable. Sometimes it is necessary to extend the veneers onto occlusal, lingual, or proximal surfaces to cover defective tooth structure. This article will define "full veneers," present indications, show preparation designs, and present clinical cases where full veneers have been used. PMID- 8205585 TI - Computers in dentistry--clinical applications. PMID- 8205586 TI - Toothbrush abrasion: prevention and the Alert toothbrush. PMID- 8205587 TI - Impression considerations in the maxillary anterior region. AB - This article discusses the precautions necessary to obtain a predictable gingival condition for achieving optimum esthetic results. The timing of the final impression is also discussed in this context. PMID- 8205588 TI - Esthetic implant restorations. AB - The success achieved with osseointegrated implants in the treatment of edentulous patients created a demand for their use in partially edentulous patients as well. New challenges confronted restorative clinicians with this group of patients, particularly esthetic challenges. New components and techniques had to be developed to improve the esthetic results. The "UCLA" abutment allows the restoration to connect directly to the implant fixture, emerging through the mucosa with a natural appearance. Esthetic titanium abutments can now also be used for a subgingival restorative design that creates a natural and gradual emergence profile similar to the UCLA abutment while maintaining more of the time tested biomechanical principles of the older cylindrical titanium abutments. PMID- 8205589 TI - Design of an automatic impression testing machine. PMID- 8205590 TI - Autogenous veneer grafting for improved esthetics with dental implants. PMID- 8205591 TI - An orthodontic view of dentofacial esthetics. AB - Although beauty may be in the eye of the beholder, there appears to be an achievable balance of facial proportions that creates a pleasing appearance. This article will present the methods used by orthodontists to measure facial features and the relationship of the soft tissue to the underlying hard tissue in relation to the procedures used in changing facial growth and appearance. PMID- 8205592 TI - Treatment of patients with Zollinger-Ellison syndrome. AB - In the treatment of Zollinger-Ellison syndrome patients with severe disease and acid hypersecretion, proton pump inhibitors are the drugs of choice. Data have now been accumulated on lansoprazole treatment of 41 patients (21 treated at the National Institutes of Health [NIH], Bethesda, Maryland, USA, and 20 treated at the Bichat-Claude Bernard Hospital, Paris, France). Short-term studies of the inhibitory action of lansoprazole on acid secretion have been carried out in both institutions. Our group first performed a dose-response analysis of the efficacy of lansoprazole in reducing basal acid output (BAO) in four patients with severe Zollinger-Ellison syndrome (mean BAO 52 +/- 9 [SD] mmol H+/h) who had previously been treated with a mean omeprazole dosage of 75 mg/day. The maximum acid inhibitory effect was obtained with lansoprazole 60-90 mg/day. The 40-hour duration of action of lansoprazole appears equivalent to that of omeprazole. In a second study at the Bichat-Claude Bernard Hospital, nine Zollinger-Ellison syndrome patients underwent 24-hour intragastric pH monitoring while receiving lansoprazole (mean dosage 80 mg/day, range 30-165 mg/day) or omeprazole (mean dosage 75 mg/day, range 20-180 mg/day). The acid inhibitory activity of the two drugs was comparable. Those patients are currently receiving long-term maintenance treatment with lansoprazole, and satisfactory clinical and biological secretory control has been achieved. The long-term safety and efficacy of lansoprazole administration were studied in the 21 patients followed at the NIH. In those patients the initial maintenance dose was determined using acid inhibition studies; in all patients lansoprazole controlled gastric acid hypersecretion and peptic symptoms in both the short and long term. The mean initial maintenance dose was 60 mg QID, except for two patients who required 60 mg BID. During long-term treatment (mean duration 31 months, range 1-43 months), six patients required a dosage increase within the first year, while the lansoprazole dose could be reduced in six others. The safety profile of lansoprazole has been excellent. Comparable results have been noted in nine Zollinger-Ellison syndrome patients during an ongoing evaluation in our institution. These studies indicate that lansoprazole is an efficacious, well tolerated antisecretory agent in patients with Zollinger-Ellison syndrome. PMID- 8205594 TI - Rationale for eradication of Helicobacter pylori infection in duodenal ulcer disease. AB - Helicobacter pylori is presently considered a major factor predisposing to the development of duodenal ulceration. The risk of duodenal disease is increased up to 15-fold in patients with H pylori-associated gastritis compared with individuals without H pylori infection. This magnitude of risk with H pylori infection is higher than that of any other known or postulated factor contributing to duodenal ulcer formation. To reclassify duodenal ulcer disease from simply being an acid-related disease to being an infectious disease may appear radical, but no questions remain concerning the essential role of H pylori in this disease. The sequence of events in the development of duodenal ulceration is based on strong circumstantial evidence. The steps by which H pylori interacts with the duodenal mucosa in forming duodenal ulcers may be as follows: 1) H pylori infection of the antral mucosa alters gastric physiology, with an increase in gastrin release and a consequent increase in gastric acid secretion. 2) The increased acid load of the bulbar-duodenal mucosa is responsible for the induction of gastric metaplasia. 3) Gastric metaplasia in the duodenal mucosa can be colonized by H pylori resulting in chronic duodenitis. 4) The interaction of H pylori with the metaplastic gastric epithelium leads to weakening of the normal mucosal integrity. At this point, a variety of factors related to H pylori itself, the host response, or the superimposition of factors such as smoking or stress may ultimately lead to ulcer formation. 5) From clinical observations, it is well established that treatment of H pylori infection without concomitant effects on acid secretion is effective in healing duodenal ulcers. More importantly, eradication of H pylori significantly reduces duodenal ulcer relapse rates. Data from clinical trials strongly suggest that H pylori eradication may cure duodenal ulcer disease. PMID- 8205593 TI - Effect of lansoprazole on Helicobacter pylori. AB - Helicobacter pylori has been identified as a major factor in duodenal ulcerogenesis. After H pylori eradication, the recurrence rate of duodenal ulcers falls dramatically and cure of this chronic relapsing disease has been claimed by several authors. H pylori eradication was first attempted with bismuth salts alone or with antibiotics. H2-receptor antagonists are not effective against H pylori, although proton pump inhibitors such as omeprazole and lansoprazole are active in vitro against H pylori. Their minimum inhibitory concentration is close to that of the imidazoles (metronidazole, tinidazole): proton pump inhibitors and imidazoles have common structural features. Consequently, lansoprazole has been tested in monotherapy and triple therapy. In monotherapy, the H pylori clearance rate with lansoprazole 30 mg during 4 weeks was 40% in our study and 19% in a study by Jhala et al. No eradication was achieved. These results were in agreement with those of another proton pump inhibitor. In triple therapy, two studies used the same regimen in nonulcer dyspepsia patients: lansoprazole 30 mg/day for 2 weeks, amoxicillin 2 g/day for 2 weeks, and tinidazole 1 g/day for 2 weeks. Pooled data from these two French trials show that H pylori eradication was achieved in 14/17 patients (82.4%). Lansoprazole administered concomitantly with two antibiotics is effective in the eradication of H pylori and is as effective as other triple therapy regimens with bismuth salts, or with other proton pump inhibitors. One of the most important problems is metronidazole resistance of H pylori strains. Antibiotics such as new macrolides (clarithromycin or roxithromycin) should be tested in a triple therapy regimen against H pylori strains with lower primary resistance. PMID- 8205595 TI - Lansoprazole and Helicobacter pylori infection. AB - Helicobacter pylori-associated gastritis is present in virtually all patients with duodenal ulcer (DU). Eradication of H pylori is associated with a highly significant decline in the recurrence rates of DU, indicating that treatments aimed at eradicating H pylori are mandatory in these patients. The novel proton pump inhibitor lansoprazole exhibits a potent antiulcer effect and, in vitro, a direct antibacterial effect against H pylori. Conflicting data have been reported on the question of whether lansoprazole is bactericidal against H pylori in vivo when administered alone. The aim of this double-blind trial was to address this issue further by comparing the effects of two different 4-week regimens (lansoprazole alone or in combination with amoxicillin) on H pylori infection in patients with DU. Patients were assessed before and after the 4-week treatment and 3 months after stopping the study medication. The ulcer healing rates at 4 weeks were similar for the two treatments while there was a trend for higher recurrence rates at 4 months in patients receiving lansoprazole alone. The frequency of high-grade H pylori infection was significantly lower in the lansoprazole and amoxicillin group both at 4 weeks (84% clearing) and 4 months. After 4 weeks of treatment there were no patients with residual H pylori-positive active antral gastritis in the lansoprazole and amoxicillin group compared with 25% in the lansoprazole alone group. Neither treatment significantly affected the IgG antibody response to H pylori either at the circulatory or the mucosal level. In contrast, the mucosal H pylori-specific IgA response was significantly enhanced after 4 weeks and more markedly after treatment with lansoprazole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205596 TI - Use of non-antacid antiulcer agents in the treatment of heartburn and dyspepsia. AB - This study examined secondary-claims data to measure the cost of using non antacid antiulcer agents to treat patients with heartburn or dyspepsia. Health care utilization data were obtained from the Pennsylvania Medicaid program. The study population comprised all enrollees with dyspepsia or heartburn, excluding those with a history of ulcers. The rate and cost of gastrointestinal-related outpatient services were examined for patients receiving antiulcer drug monotherapy. The mean age of the study population (n = 1830) was 39.1 years. Ranitidine patients (n = 856) received monotherapy for an average of 71.1 days. Cimetidine (n = 395) and famotidine (n = 255) patients received monotherapy for an average of 65.0 and 71.7 days, respectively. (Mean duration of monotherapy for the other four groups ranged from 58.0 to 112.6 days). On average, there were 0.83 prescriptions issued, 0.21 physician visits, and 0.23 outpatient hospital visits per patient-month across all treatment groups. The average cost to the Pennsylvania Medicaid program was approximately $68 monthly per patient. Drugs accounted for the majority of these costs ($51.04), followed by surgical/diagnostic procedures ($5.13), outpatient hospital visits ($4.89), and physician visits ($4.15). PMID- 8205597 TI - Predictors of medication noncompliance in a sample of older adults. AB - The subjects were 1028 respondents from a randomly selected sample of independently living adults aged 55 years and older in the southeastern United States. Data on background characteristics, physical health, life satisfaction, psychological distress, and medication compliance were gathered from structured interviews. Among the 785 subjects in the analysis who were taking prescribed medications, 75% were women, 83% were white, their median income was $12,500 annually, 66% lived alone, their mean age was 73.9 years, and their mean number of years of education was 11.4. Twenty-one percent of all respondents taking medications had been noncompliant during the month preceding the study interview. Noncompliance with prescribed medications was significantly associated with higher socioeconomic status (P < 0.01), greater number of prescribed medications (P < 0.01), and higher psychological stress (P < 0.05). There was no relationship between compliance and living arrangements, health, life satisfaction, number of illnesses, age, or sex. PMID- 8205598 TI - Therapeutic use of lovastatin in the treatment of hypercholesterolemia. AB - The present review discusses the mechanism of action, efficacy, safety profile, and potential uses of lovastatin in patients with hypercholesterolemia. Data on the efficacy of lovastatin are evaluated in different patient populations; also, the efficacy of this agent in the long-term treatment of patients followed by the author is presented. No new safety concerns have emerged during long-term treatment of selected patients with lovastatin, and, in compliant patients, hypolipidemic effects are maintained during continuous treatment with therapy that exceeds 5 years. On the basis of available data, lovastatin should be regarded as one of the drugs of first choice in the treatment of adult patients with hypercholesterolemia and increased plasma concentrations of low-density lipoproteins. PMID- 8205599 TI - Amphotericin B use in a major acute care hospital. AB - A retrospective study was undertaken to assess the use of the antifungal agent amphotericin B in a major acute care hospital. Data were reviewed from 82 patients who were prescribed amphotericin B at Vancouver General Hospital between March 1 and September 1, 1990. Sixty-one percent of the patients treated with amphotericin B were from the hematology service, 22% were from the intensive care unit (ICU) service, and the remainder were from other hospital services. Fever of unknown origin was the most common reason for amphotericin B use in the hematology patients, while candidemia was most prevalent in the ICU patients. Renal dysfunction during treatment was common and related to the dose received. Test doses were used in the majority of courses, and premedications were also common. Cumulative doses administered were typically lower than intended. Amphotericin B treatment was considered successful in 46% of the cases reviewed. This review provides insight into how amphotericin B is used at one hospital and how this use may be improved. Potential applications for fluconazole are also discussed. PMID- 8205600 TI - Use of a premixed insulin regimen (Novolin 70/30) to replace self-mixed insulin regimens. AB - The efficacy and safety of transferring 76 patients with poorly controlled type II diabetes mellitus from various self-mixed human insulin regimens to a premixed insulin regimen (Novolin 70/30, 70% NPH and 30% Regular insulin, semisynthetic) were evaluated in a 24-week, multicenter, open-label study. During the initial 12 week run-in period, the patients received twice-daily doses of NPH and Regular human insulin mixed in ratios of 60/40, 80/20, 90/10, or NPH alone, as recommended by their physicians. Subsequently, these patients were transferred to a regimen of Novolin 70/30 twice daily for an additional 12 weeks. In most cases, the transfer was made on a dose-for-dose basis. Following the transfer from self mixed to premixed insulin, the mean glycated hemoglobin fell from 9.3% to 8.7% at 6 weeks (P < 0.001) and to 8.5% at 12 weeks (P < 0.001). This improved glycemic control was not accompanied by an increase in the frequency or severity of hypoglycemic episodes. It is concluded that patients with type II diabetes mellitus who are poorly controlled on a wide range of self-mixed insulin ratios can be safely transferred, often in a dose-for-dose fashion, to a more convenient 70/30 premixed regimen. PMID- 8205601 TI - Synergized pyrethrin mousse, a new approach to head lice eradication: efficacy in field and laboratory studies. AB - The purpose of this study was to evaluate the pediculicidal and ovicidal efficacy of a new, single-application formulation of synergized natural pyrethrins (presented in an aerosol mousse form) compared with an established, effective formulation based on permethrin (in a creme rinse form). The trial was a single blind, comparative, randomized, parallel-group study. Children between the ages 7 and 15 years and adults with active head lice infections, identified by the presence of live lice, were enrolled from a school and a children's home in Dhaka, Bangladesh. Prevalence of infection ranged from 75% to 100% in the two study centers. The field study confirmed laboratory findings showing pyrethrin mousse to be effective at killing both lice and their eggs with a single 10 minute application. Of 52 patients identified with lice, 42 were treated with pyrethrin mousse and 10 with permethrin creme rinse. In each case, a sample of viable louse eggs was taken from the patients' hair before and after treatment. The eggs were then incubated to assess ovicidal activity. After treatment, the patients were examined for lice on alternate days until day 8 and then again on day 14. None of the patients in either group was found to have lice up to 2 days after treatment. One patient was found to have two moribund hatchlings on day 4. By day 6, when any eggs still present on the scalp would be expected to hatch, 19 pyrethrin mousse-treated patients were available for assessment. Two patients had been reinfected from contacts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205602 TI - Effect of propentofylline and pentoxifylline on cerebral blood flow using 123I IMP SPECT in patients with cerebral arteriosclerosis. AB - Propentofylline and pentoxifylline were administered to patients age 65 years or older who were suffering from chronic cerebrocirculatory insufficiency. Changes in clinical symptoms and the level of cerebral blood flow before and after drug administration were compared. 123I-IMP single photon emission computed tomography was used to compare cerebral blood flow before treatment with that 3 months after initiation of therapy. Focal regions of interest were established in the cerebellum, the frontal, temporal, parietal, and occipital lobes, and the thalamus. Comparisons were made between patients age 75 years or older (very old age group) (n = 5) and those age 65 to 74 years (old age group) (n = 7). Complaints of dizziness and slight headache disappeared by the eighth week after the start of therapy in both age groups. Two of the five patients in the very old age group showed elimination of memory disturbance symptoms at the 12th week of treatment. Six of the seven patients in the old age group had no memory disturbance symptoms by the eighth week of treatment, which indicates a high therapeutic effect in this group. In the cerebral blood flow studies, no increases in blood flow after drug administration were observed in the very old age group. This finding is probably related to the poor level of recovery achieved in disturbances in memory in this group. In contrast, improvements in blood flow were observed for all regions of the brain monitored in the old age group, which is consistent with the amelioration of clinical symptoms observed in these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205603 TI - Effects of the angiotensin II receptor antagonist, TCV-116, on blood pressure and the renin-angiotensin system in healthy subjects. AB - TCV-116 is a new, nonpeptide, angiotensin II type-1 receptor antagonist that acts as a specific inhibitor of the renin-angiotensin system. In this study, 36 healthy male volunteers were administered single and repeated oral doses of TCV 116 to investigate its effects on blood pressure and heart rate, and to evaluate the safety and pharmacokinetics of the drug. At single doses of 2.5 mg and greater, TCV-116 significantly lowered blood pressure even in normotensive subjects. This hypotensive effect was maintained during repeated administration on a once-daily regimen over an 8-day period. Serum concentration of M-1, an active metabolite of TCV-116, increased in a dose-dependent manner, reaching a peak 3 to 4 hours after administration. An amount of M-1 equivalent to approximately 10% of the administered dose of TCV-116 was excreted in the urine during the first 24 hours following administration. No accumulation of M-1 was observed in subjects receiving repeated administration of TCV-116. No adverse effects were observed except for mild headache in three subjects. These results suggest that the renin-angiotensin system plays a role in the regulation of blood pressure, even in normotensive subjects, and that TCV-116 may prove to be useful in the treatment of hypertension. PMID- 8205604 TI - The efficacy of chemotherapy and splenic irradiation in the management of chronic myelogenous leukaemia at Ibadan, Nigeria. AB - Chronic myelogenous leukaemia (CML) in Nigerians shows a male predominance over females as has been observed in other centres. Out of 25 patients treated between 1987 and 1990, 18 were male. The mean survival of CML patients on chemotherapy was 48.7 months with a median of 38 months, while the mean survival of patients who had chemotherapy plus splenic irradiation was 53.3 months with a median survival of 53 months. The difference between the two mean survival rates was non significant. Splenic irradiation resulted in significant reduction in splenic size with total disappearance of gastrointestinal symptoms. The need for red cell and blood products transfusion diminished. Patients had a feeling of well being though short-lived. In a developing country, the added cost of irradiation must be weighted against the relatively brief improvement in well-being when deciding mode of management of the disease. Cause of death in all cases was septicaemia, complications of thrombocytopaenia and marrow failure. PMID- 8205605 TI - In vitro responses of P. falciparum parasites to chloroquine, amodiaquine and quinine in two ecological zones in Ghana. AB - Blood specimens were taken from 318 school children with at least 1,000 and not more than 80,000 P. falciparum asexual parasites per microliter of blood for a 30 hour in vitro microtest of P. falciparum asexual parasites responses to chloroquine, amodiaquine and quinine. The study was conducted in primary schools in four urban and three rural communities in the costal and forest zones in Ghana between June 1988 and December 1990. Chloroquine resistance was present in 58.7 pc (54/92) and 3.9 pc (4/103) of the successful in vitro tests in the coastal and forest zones respectively. Resistance to amodiaquine was recorded in 28.6 pc (12/42) of the successful tests in coastal zone. There was no resistance to quinine in any of the ecological zones. Concentrations of the three drugs in pmol required for 90 pc inhibition of schizont maturation were generally higher in communities in the coastal zone than those in the forest zone. The results suggest an increase in sensitivity or a reduction in resistance of P. falciparum to the drugs from the coast to the forest zone. PMID- 8205606 TI - Antifungal activity of essential oil from Artemisia afra Jacq. AB - Artemisia afra is indigenous to the eastern highlands of Zimbabwe where it is used in folk medicine. Hydro-distilled volatile oil from the aerial parts of the plant was tested for antifungal activity against 10 fungal species using the dry weight method. The results obtained showed that the essential oil exhibited significant activity against Aspergillus ochraceus, Candida albicans, Alternaria alternata, Geotrichum candidum, Aspergillus niger, Penicillium citrium and Aspergillus parasiticus. PMID- 8205607 TI - In vivo evaluation of iron bioavailability in some Nigerian peasant meals by haemoglobin regeneration technique. AB - The bioavailability of iron in three different rural Nigerian peasant meals was studied. The meals were: pounded yam (Discorea spp) with 'afia efere'--(plain soup); 'ekpang nkukwo'--grated cocoyam (Xanthosoma maffafa Schott) and cocoyam leaves with pepper and plantain porridge (Musa paradisiaca) with water leaf (Talinum triangulare). Analyses of the meals showed the protein content to range from 8.58 +/- 0.01 mg/100 g DM to 11.38 +/- 0.08/100g DM. Iron content ranged from 17.50 +/- 2.50 mg/100 DM to 23.94 +/- 3.56 mg/100g DM. The rehabilitation of mildly anaemic rats with test meals showed the percentage of the ingested iron utilised for haemoglobin synthesis as: 48.08 +/- 0.51 pc; 18.09 +/- 0.41 pc; 19.09 +/- 0.36 pc for the test diets respectively and 60.80 +/- 0.22 pc for the control group. A comparison of the utilization of iron between the test and the control groups showed that there was a significant difference (p < 0.01) between the test and the control groups. The low level of iron enhancers in the meals has been suggested as the possible cause of the marginal level of iron availability from the meals to the test animals. PMID- 8205608 TI - Epididymal metastasis as the first presenting feature of an asymptomatic caecal cancer. PMID- 8205609 TI - Beckwith-Wiedemann syndrome in Bulawayo, Zimbabwe. AB - Beckwith-Wiedemann syndrome is an easily recognised syndrome in its complete form with macroglossia and exomphalos. The three cases reported here are an attempt to increase awareness of the existence of this syndrome which has serious consequences. All our patients had the combination of macroglossia and exomphalos, but none developed symptomatic hypoglycaemia. Growth patterns were distinctly different in all cases. One patient was the first of a pair of twins. The syndrome is inherited in an autosomal dominant fashion with incomplete penetrance and variable expressivity. Early diagnosis should alert the clinician to the risk of eventual neonatal hypoglycaemia and long term follow up is warranted because of a possible development of malignancies in childhood. The reason for the very low incidence of the syndrome in Bulawayo remains unexplained. PMID- 8205610 TI - Dystrophin-associated proteins and synapse formation: is alpha-dystroglycan the agrin receptor? PMID- 8205611 TI - Telomeres: no end in sight. PMID- 8205612 TI - A putative novel class of animal lectins in the secretory pathway homologous to leguminous lectins. PMID- 8205613 TI - Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. PMID- 8205614 TI - Imprinting and X chromosome counting mechanisms determine Xist expression in early mouse development. AB - In mice, X inactivation is preceded by in cis Xist expression. Initially, normal female embryos express the paternal Xist allele exclusively, preceding imprinted X inactivation in the trophectoderm. Later expression of Xist alleles is random, preceding random X inactivation in the epiblast lineage. In this study using uniparental embryos, we demonstrate that Xist expression is initially dictated solely by parental imprinting, causing expression of all paternal alleles. Maternal alleles remain repressed, irrespective of X chromosome number. At the compacting morula stage, this parental imprint is erased, and the mechanism counting the X chromosomes imposes appropriate Xist expression with respect to chromosome number. Our results also suggest that Xist expression may itself be regulated by a novel imprinted maternally expressed gene. PMID- 8205615 TI - Nuclear receptor steroidogenic factor 1 regulates the mullerian inhibiting substance gene: a link to the sex determination cascade. AB - Normal male sex differentiation requires that Sertoli cells in the embryonic testes produce mullerian inhibiting substance (MIS), a TGF beta-like hormone that causes mullerian duct regression. In primary Sertoli cells, the orphan nuclear receptor, steroidogenic factor 1 (SF-1), regulates the MIS gene by binding to a conserved upstream regulatory element. In heterologous (HeLa) cells, MIS gene activation by SF-1 requires removal of the SF-1 ligand-binding domain, implicating a Sertoli cell-specific ligand or cofactor. Finally, the sexually dimorphic expression of SF-1 during development coincides with MIS expression and mullerian duct regression. We propose that SF-1 regulates MIS in vivo and participates directly in the process of mammalian sex determination. PMID- 8205616 TI - A role for dystrophin-associated glycoproteins and utrophin in agrin-induced AChR clustering. AB - Synapse formation is characterized by the accumulation of molecules at the site of contact between pre- and postsynaptic cells. Agrin, a protein implicated in the regulation of this process, causes the clustering of acetylcholine receptors (AChRs). Here we characterize an agrin-binding site on the surface of muscle cells, show that this site corresponds to alpha-dystroglycan, and present evidence that alpha-dystroglycan is functionally related to agrin activity. Furthermore, we demonstrate that alpha-dystroglycan and adhalin, components of the dystrophin-associated glycoprotein complex, as well as utrophin, colocalize with agrin-induced AChR clusters. Thus, agrin may function by initiating or stabilizing a synapse-specific membrane cytoskeleton that in turn serves as a scaffold upon which synaptic molecules are concentrated. PMID- 8205617 TI - Dystroglycan-alpha, a dystrophin-associated glycoprotein, is a functional agrin receptor. AB - Aggregation of acetylcholine receptors (AChRs) on skeletal muscle fibers is thought to be mediated by the basal lamina protein agrin. Structural similarities shared by agrin and laminin suggested that the laminin receptor dystroglycan alpha, part of a dystrophin-receptor complex, might also bind agrin. We show here that dystroglycan-alpha and dystrophin-related protein (DRP/utrophin) are concentrated within AChR aggregates in cultures of C2 myotubes and that agrin binds specifically to dystroglycan-alpha in in vitro assays. This binding is calcium dependent and is inhibited by monoclonal antibody (MAb) IIH6 against dystroglycan-alpha, heparin, and laminin, but not by fibronectin. In S27 cells, which do not aggregate AChRs spontaneously, agrin and laminin binding to dystroglycan-alpha are dramatically decreased. Moreover, MAb IIH6 significantly inhibits agrin-induced AChR aggregation on C2 cells. We conclude that dystroglycan-alpha is an agrin-binding protein and part of a dystrophin-receptor complex involved in AChR aggregation. PMID- 8205618 TI - Patterns of cell movement within the Dictyostelium slug revealed by cell type specific, surface labeling of living cells. AB - There are cells scattered in the rear, prespore region of the Dictyostelium slug that share many of the properties of the prestalk cells and that are therefore called anterior-like cells (ALCs). By placing the gene encoding a cell surface protein under the control of an ALC-specific promoter and immunologically labeling the living cells, we analyze the movement of ALCs within the slug. There is a posterior to anterior cellular flow, and the ALCs change their movement pattern as they enter the prestalk zone. Prestalk cells are periodically shed from the migrating slug. They must be replaced if the correct ratio of prestalk to prespore cells is to be maintained, and we present evidence for the transdifferentiation of prespore into prestalk cells, with ALCs functioning as intermediates in the transition. The slug has, therefore, a surprisingly dynamic structure, both with respect to cellular differentiation and cell movement. PMID- 8205619 TI - Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. AB - We demonstrate that missense mutations (Asp175Asn; Glu180Gly) in the alpha tropomyosin gene cause familial hypertrophic cardiomyopathy (FHC) linked to chromosome 15q2. These findings implicated components of the troponin complex as candidate genes at other FHC loci, particularly cardiac troponin T, which was mapped in this study to chromosome 1q. Missense mutations (Ile79Asn; Arg92Gln) and a mutation in the splice donor sequence of intron 15 of the cardiac troponin T gene are also shown to cause FHC. Because alpha-tropomyosin and cardiac troponin T as well as beta myosin heavy chain mutations cause the same phenotype, we conclude that FHC is a disease of the sarcomere. Further, because the splice site mutation is predicted to function as a null allele, we suggest that abnormal stoichiometry of sarcomeric proteins can cause cardiac hypertrophy. PMID- 8205620 TI - Nerve growth factor activates a Ras-dependent protein kinase that stimulates c fos transcription via phosphorylation of CREB. AB - A mechanism by which the nerve growth factor (NGF) signal is transduced to the nucleus to induce gene expression has been characterized. An NGF-inducible, Ras dependent protein kinase has been identified that catalyzes the phosphorylation of the cyclic AMP response element-binding protein (CREB) at Ser-133. Phosphorylation of Ser-133 stimulates the ability of CREB to activate transcription in NGF-treated cells. These findings suggest that CREB has a more widespread function than previously believed and functions in the nucleus as a general mediator of growth factor responses. PMID- 8205621 TI - JNK is involved in signal integration during costimulation of T lymphocytes. AB - T lymphocyte activation and interleukin-2 (IL-2) production require at least two signals, generated by phorbol ester (TPA) and Ca2+ ionophore or costimulation of the T cell receptor (TCR) and the CD28 auxiliary receptor. We investigated how these stimuli affect mitogen activated protein (MAP) kinases. Full activation of the MAP kinases that phosphorylate the Jun activation domain, JNK1 and JNK2, required costimulation of T cells with either TPA and Ca2+ ionophore or antibodies to TCR and CD28. Alone, each stimulus resulted in little or no activation. Similar to its effect on IL-2 induction, cyclosporin A (CsA) inhibited the synergistic activation of JNK, and a competitive inhibitor of Jun phosphorylation by JNK inhibited IL-2 promoter activation. By contrast, the MAP kinases ERK1 and ERK2 were fully activated by TPA or TCR stimulation and were not affected by Ca2+, CD28, or CsA. Hence, integration of signals that lead to T cell activation occurs at the level of JNK activation. PMID- 8205622 TI - A class switch control region at the 3' end of the immunoglobulin heavy chain locus. AB - We replaced the IgH 3' enhancer (3'EH) region with a neomycin resistance gene in ES cells and generated chimeric mice in which all mature lymphocytes were either heterozygous (3'EH+/-) or homozygous (3'EH-/-) for the mutation. In vitro activated 3'EH-/- B cells responded similarly to 3'EH+/- B cells with respect to proliferation and secretion of IgM and IgG1 but were specifically deficient in IgG2a, IgG2b, IgG3, and IgE secretion. These isotype deficiencies correlated with a deficiency in accumulation of transcripts from and class switching to affected CH genes. In vivo, chimeric mice containing only 3'EH-/- B cells were deficient in serum IgG2a and IgG3. We propose that the 3'EH-/- mutation disrupts the activity of a regulatory region that influences heavy chain class switching to several different CH genes that lie as far as 100 kb upstream of the mutation. PMID- 8205623 TI - Transcriptional elongation by RNA polymerase II is stimulated by transactivators. AB - We report that a variety of transactivators stimulate elongation by RNA polymerase II. Activated transcription complexes have high processivity and are able to read through pausing and termination sites efficiently. In contrast, nonactivated and "squelched" transcription mostly arrests prematurely. Activators differ in the extent to which they stimulate processivity; for example, GAL4-VP16 and GAL4-E1a are more effective than GAL4-AH. The stimulation of elongation can be as important as the stimulation of initiation in activating expression of a reporter gene. We suggest that setting the competence of polymerase II to elongate is an integral part of the initiation step that is controlled by activators cooperating with the general transcription factors. PMID- 8205624 TI - Force and velocity measured for single kinesin molecules. AB - We measured the force-velocity curves of single kinesin molecules attached to silica beads moving in an in vitro motility assay. Optical trapping interferometry was used to track movement with subnanometer precision and to apply calibrated, pN-sized forces to the beads. Velocity decreased linearly with increasing force, and kinesin molecules moved against applied loads of up to 5-6 pN. Comparison of force-velocity curves at limiting and saturating ATP concentrations suggests that the load-dependent diminution in kinesin velocity may be due to a decrease in the net displacement per molecule of ATP hydrolyzed, not simply to a slowing of the ATP turnover rate; kinesin would therefore appear to be a loosely coupled motor. PMID- 8205625 TI - AIDS-related fear: beliefs, attitudes, behaviors. PMID- 8205626 TI - Successful removable prosthodontics. PMID- 8205627 TI - Investment for the new professional. PMID- 8205628 TI - Continuing education requirements: what's it all about? PMID- 8205629 TI - Preparing for retirement. PMID- 8205630 TI - Dentistry changing the face of sports. PMID- 8205632 TI - Why pay dues? PMID- 8205631 TI - Safe and effective vital tooth bleaching. PMID- 8205633 TI - Last call at the MSI. PMID- 8205634 TI - Centric relation or centric occlusion? Choosing the best restorative procedure. PMID- 8205635 TI - The thoughtfully constructed portfolio. PMID- 8205636 TI - CDS keeps an ear to the ground. PMID- 8205637 TI - Immunization in urban areas: issues and strategies. AB - In the past, immunization programmes have focused primarily on rural areas. However, with the recognition of the increasing numbers of urban poor, it is timely to review urban immunization activities. This update addresses two questions: Is there any need to be concerned about urban immunization and, if so, is more of the same kind of rural EPI activity needed or are there specific urban issues that need specific urban strategies? Vaccine-preventable diseases have specific urban patterns that require efficacious vaccines for younger children, higher target coverage levels, and particular focus to ensure national and global eradication of poliomyelitis. Although aggregate coverage levels are higher in urban than rural areas, gaps are masked since capital cities are better covered than other urban areas and the coverage in the poorest slum and periurban areas within cities is as bad as or worse than that in rural areas. Difficult access to immunization services in terms of distance, costs, and time can still be the main barrier in some parts of the city. Mobilization and motivation strategies in urban areas should make use of the mass media and workplace networks as well as the traditional word-of-mouth strategies. Use of community health workers has been successful in some urban settings. Management issues concern integration of the needs of the poor into a coherent city health plan, coordination of different health providers, and clear lines of responsibility for addressing the needs of new, urbanizing areas. PMID- 8205638 TI - The pathogenetic aspects of measles virus infection: memorandum from a WHO meeting. AB - Over the last three years considerable progress has been made in various areas related to measles virus and infection. A meeting to discuss the currently available data on the molecular biology of measles virus, measles immunology, immunopathology, as well as animal models for measles infection, and to identify studies that need to be carried out towards developing new vaccines was organized jointly by WHO and the U.S. National Institutes of Health and held in Montreux, Switzerland, on 20-21 April 1993. This Memorandum summarizes the discussions and recommendations made by the participants. PMID- 8205639 TI - Laboratory diagnosis of measles infection and monitoring of measles immunization: memorandum from a WHO meeting. AB - Measles infection continues to be a major global health problem, and in many countries the disease is frequently diagnosed on clinical grounds alone, although it is easily confused with other conditions. In order to discuss approaches to improving this situation, a WHO Consultation on Laboratory Diagnosis of Measles Infection and Monitoring of Measles Immunization was held in Glasgow on 7-8 August 1993. The discussions and recommendations made by the participants are summarized in this Memorandum. PMID- 8205640 TI - Global tuberculosis incidence and mortality during 1990-2000. AB - Forecasts of tuberculosis morbidity and mortality are presented for the decade 1990-99. An estimated 88 million new cases of tuberculosis, of which 8 million will be attributable to HIV infection, will occur in the world during the decade; 30 million people are predicted to die of tuberculosis in the same period, including 2.9 million attributable to HIV infection. The number of new tuberculosis cases occurring each year is predicted to increase from 7.5 million (143 cases per 100,000) in 1990 to 8.8 million (152 per 100,000) in 1995 and 10.2 million (163 per 100,000) in the year 2000. In 1990, 2.5 million persons were estimated to have died of tuberculosis; at the same level of availability of treatment, it is predicted that 3.0 million tuberculosis deaths will occur in 1995 and 3.5 million in 2000. Demographic factors, such as population growth and changes in the age structure of populations, will account for 79.5% of the predicted increases in new cases. Age-specific incidence rates in sub-Saharan Africa are increasing due to the HIV epidemic and will account for the remaining 20.5% of the forecast increase in new cases. In WHO's South-East Asian Region and in Central and South America the age-specific incidence rates are expected to fall during 1990-2000, but at a slower rate than in previous years because of the expected increase in HIV seroprevalence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205641 TI - Lessons from Cuba: mass campaign administration of trivalent oral poliovirus vaccine and seroprevalence of poliovirus neutralizing antibodies. AB - The immunogenicity of trivalent oral poliovirus vaccine (TOPV), which is less effective in tropical than in temperate areas, may potentially be improved in several ways, including increasing the number of doses. Little information is available on TOPV when more than 6 doses are given. The situation in Cuba provides a unique opportunity to relate the seroprevalence of neutralizing antibodies to the dose of TOPV because Cuba has not reported culture-confirmed poliomyelitis since 1973 and TOPV is only administered in twice yearly 1-week mass immunization campaigns. Sera from 2000 children nationwide were studied for neutralizing antibody among children who received 0, 2, 4, 6 and 8 doses of TOPV. These doses were administered in the period 1989-91, when TOPV (from the USSR) was being used with 500,000, 200,000, and 300,000 median tissue-culture-infecting doses (TCID50) for types 1, 2 and 3, respectively--the 5:2:3 formulation. Seroprevalence of neutralizing antibody after two TOPV doses was 91.5% for type 1, 90.8% for type 2, and 45.9% for type 3. Seroprevalence of type-3 neutralizing antibody after 6 doses remained low (73.4%), but increased to 83.5% after 8 doses (P < 0.05). Although 16.5% of the children remained unprotected for type-3 infection even after 8 doses, mass campaign immunization strategies were sufficient to eradicate the transmission of wild poliovirus in Cuba. Because the seroprevalence of type-1 neutralizing antibody was high (91.5%) after two campaign doses, additional studies using different formulations are needed to determine whether simultaneous improvement in the type-3 response to two campaign doses can be achieved. PMID- 8205642 TI - Measles control in Maputo, Mozambique, using a single dose of Schwarz vaccine at age 9 months. AB - In Maputo city, immunization is available at government health facilities, all contacts being used to vaccinate children. Door-to-door mobilization is conducted to identify eligible children and refer them for immunization. Card-documented measles vaccine coverage, estimated by community surveys, rose from 48% in 1982 to 86% in 1986 and 92% in 1992. The median age at measles vaccination was 10.2 months in 1986 and 9.2 months in 1992. The reported measles incidence rates per 100,000 population fell by 92% from 569 in 1977-78 (pre-vaccination) to 44 in 1990-92, and the reported inpatient measles mortality fell from 19.8 to 0.7 per 100,000. Among children whose age at measles onset was known, the proportion of reported measles cases in children under 9 months of age fell from 2162 (20.3% of 10,636 cases) in 1982-85 to 1695 (17.8% of 9501 cases) in 1986-92. The proportion of cases in children aged > or = 5 years increased from 15.2% to 32.8% in the corresponding periods. The global goals for measles control can be achieved by a single dose of Schwarz vaccine at 9 months of age. PMID- 8205644 TI - Quality of sexually transmitted disease services in Jamaica: evaluation of a clinic-based approach. Collaborative Working Group on Indicators of STD Case Management. AB - As part of a larger strategy to develop global indicators of HIV (human immunodeficiency virus) infection prevention programmes, a clinic-based method for the assessment of sexually transmitted disease (STD) service quality was developed and field tested by trained observers who visited a random sample of public-sector clinics in Jamaica in October 1991. The assessment included an inventory of equipment and drugs, interviews with clinic staff, and observations of 27 health workers in 15 clinics as they provided services to 115 patients presenting for STD care. This observation-based method provided Jamaican programme managers with descriptive data on STD case management in public clinics within a one-month study period at an approximate local cost of US+ 5000. Based on weighted estimates, 91% of public-sector STD patients in Jamaica were seen in clinics whose staff had received some training in STD case management during the preceding 12 months. The correct treatment rate was estimated to be 82% for those diagnosed with gonorrhoea, and 70% for those diagnosed with syphilis. Based on 98 observed encounters for first-time-for-episode patients, counselling included sex partner referral (57%), partner reduction (48%), and condom use (59%). Although 61% of STD patients were seen in clinics with condoms in stock on the day of the assessment, only 23% were offered condoms during their visit. The clinic-based assessment method can be adapted to the programme management and reporting needs of countries at all stages of STD service development, and can provide data needed to improve programme operations and meet international reporting standards. PMID- 8205643 TI - Comparison of oral artesunate and quinine plus tetracycline in acute uncomplicated falciparum malaria. AB - In Thailand Plasmodium falciparum malaria is highly resistant to available antimalarials. Investigations on the efficacy of existing antimalarials and of alternative drugs are urgently needed. Artesunate has been shown to be effective against falciparum malaria, but is associated with a high recrudescence rate. We have carried out a comparative clinical trial of the standard regimen of quinine + tetracycline versus oral artesunate at a 700-mg total dose given over 5 days to patients with acute uncomplicated falciparum malaria. The 64 male patients who took part in the study were randomized to receive either quinine-tetracycline (33 patients) or oral artesunate (31 patients). All the patients were admitted to the Bangkok Hospital for Tropical Diseases for 28 days. Oral artesunate had faster parasite and fever clearance times than the combination quinine-tetracycline, but the cure rate was not significantly different for the two regimens. However, the occurrence of adverse effects, such as tinnitus, was significantly higher in the quinine-tetracycline group. Surprisingly nausea and dizziness were rather common with artesunate. The possibility of neurological adverse effects for artesunate should also be borne in mind. Oral artesunate (700 mg given over 5 days) is effective and better tolerated than the combination quinine-tetracycline. The cure rate we obtained is higher than that reported in previous studies with 600 mg of oral artesunate given over 5 days. Oral artesunate can be considered as an alternative drug for multiple-drug-resistant falciparum malaria; however, adverse effects, particularly neurotoxicity, should be closely monitored before its widespread use can be recommended.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205645 TI - [Multicenter study of toxoplasma serology using various commercial ELISA reagents. Work Group Toxoplasmosis of the National Agency for Quality Control in Parasitology]. AB - A collaborative study conducted by the French National Agency for Quality Control in Parasitology (CNQP) and various manufacturers of ELISA kits, represented by the Association of Laboratory Reagent Manufacturers (SFRL) compared the toxoplasmosis IgG antibody titres obtained with different ELISA-IgG kits and determined the relationships between the titres obtained by these techniques and the titre defined in international units (IU). Fifty-one serum samples with toxoplasmosis antibody titres ranging from 0 to 900 IU were tested in two successive studies with 16 ELISA-IgG kits. For the negative sera, false-positive reactions were observed with one kit. For the positive sera, the titres observed in ELISA were generally higher than those expressed in IU. Above 250 IU, the very wide variability of the titres found with the different ELISA kits renders any comparative analysis impossible. For titres below 250 IU, the results are sufficiently homogeneous to permit the use of regression analysis to study how the results for each ELISA kit compare with the mean results for the other kits. The slope of the line of regression shows a tendency to over-titration or under titration compared with the results of the other manufacturers; the ordinate at the origin reflects the positivity threshold of the reaction and can be used to assess the risk of a lack of sensitivity (high threshold) or of specificity (threshold too low). On the whole, the trends revealed for a given manufacturer are constant from one study to the other. Within this range of titres, regression analysis also reveals the general tendency of ELISA kits to overestimate the titres by comparison with immunofluorescence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205646 TI - Priorities for pharmaceutical policies in developing countries: results of a Delphi survey. AB - The use of the Delphi method as a systematic and logical approach to establishing consensus among international experts on the priorities for interventions in national drug policies in developing countries is described. The Delphi survey showed a high degree of reliability, as evidenced by the high response rate, the quality of respondents, and the high standard for consensus. In addition to creating consensus on key issues and key components for priority intervention, the study identified six components that could constitute a basic framework for designing drug policy in developing countries. The study's conclusions have important implications for decision-makers within international development agencies and national governments. PMID- 8205647 TI - A baseline survey on use of drugs at the primary health care level in Bangladesh. AB - The drug use pattern and the quality of care were assessed in 80 public sector facilities throughout rural Bangladesh. A total of 40 thana health complexes and 40 union subcentres, the lowest level in primary health care facilities, were selected at random. A total of 2880 prescriptions, consultations, and drug dispensing practices were studied, and the availability and use of essential drugs and of the essential drugs list were recorded. The average consulting time (54 seconds), the proportion of adequate examinations (37%), and prescription of drugs according to standard treatment guidelines (41%) were unsatisfactory. The mean number of drugs prescribed per patient was 1.44; 25% were treated with antibiotics, and 17% with metronidazole, irrespective of the diagnoses. The availability of drugs (54%) and the presence of an essential drugs list (16%) in the health facilities were low. However, 78% of the drugs were prescribed by their generic names, 85% complied with the essential drugs list, and 81% were dispensed according to prescription. The average dispensing time (23 seconds) and the proportion of patients who correctly understood the dosage (55%) were poor. PMID- 8205648 TI - Issues in the assessment of nutritional status using anthropometry. AB - Four issues in the use and interpretation of anthropometry are discussed at the level of the population and of the individual. The first issue is the index or indices of choice: weight-for-height versus height-for-age versus weight-for-age. The selection of an index or indices depends upon many factors, and no one index is completely adequate in all situations. Proposed criteria are provided to assess the severity of low anthropometry within populations. The second issue is the scale of the index: z-scores (or standard deviations) versus percentiles versus percent-of-median. z-Scores have several properties that make them superior to the other two scales. A third issue deals with limitations in the current growth reference; one of these is the disjunction between the growth curves at 2 years of age, resulting from the use of two different populations in the reference. It is important that this disjunction be recognized by researchers so that the anthropometric findings are interpreted correctly for this age range. Lastly, some issues to do with the collection of single versus multiple anthropometric measurements on children are discussed. PMID- 8205650 TI - Tuberculosis preventive therapy in HIV-infected individuals. PMID- 8205649 TI - Public health surveillance: historical origins, methods and evaluation. AB - In the last three decades, disease surveillance has grown into a complete discipline, quite distinct from epidemiology. This expansion into a separate scientific area within public health has not been accompanied by parallel growth in the literature about its principles and methods. The development of the fundamental concepts of surveillance systems provides a basis on which to build a better understanding of the subject. In addition, the concepts have practical value as they can be used in designing new systems as well as understanding or evaluating currently operating systems. This article reviews the principles of surveillance, beginning with a historical survey of the roots and evolution of surveillance, and discusses the goals of public health surveillance. Methods for data collection, data analysis, interpretation, and dissemination are presented, together with proposed procedures for evaluating and improving a surveillance system. Finally, some points to be considered in establishing a new surveillance system are presented. PMID- 8205651 TI - Risk from radon gas indoors. PMID- 8205653 TI - AHA adds public education as top priority. PMID- 8205652 TI - Malaria chemoprophylactic regimens for travellers. PMID- 8205654 TI - Novel cardiac myofilament desensitizing factor released by endocardial and vascular endothelial cells. AB - BACKGROUND: Recent studies suggest that both endocardial endothelium and coronary vascular endothelium influence myocardial contraction, but the mediators responsible and their mechanisms of action are not well defined. METHODS AND RESULTS: We investigated the effects of cultured endocardial endothelial and vascular endothelial cell superfusate on contraction and intracellular calcium transients of isolated rat cardiac myocytes. Endothelial cell superfusate induced a potent negative inotropic effect, with a rapid reversible decrease in myocyte twitch amplitude, earlier twitch relaxation, and a significant increase in diastolic length. This effect was not associated with significant changes in intracellular calcium or pH; was not attributable to nitric oxide, prostanoids, cGMP, or protein kinase C activation; and did not involve pertussis toxin sensitive G proteins. The activity was stable at 37 degrees C for several hours, was not destroyed by protease treatment, and was found in low-molecular-weight (<< 1 kD) superfusate fractions. CONCLUSIONS: These data suggest the tonic release by endothelial cells of a novel, stable factor that acts predominantly by reducing the response of cardiac myofilaments to calcium (ie, "desensitizes" them). This "desensitizing factor" could rapidly modulate cardiac contraction relaxation coupling and diastolic tonus and exert distant effects because of its stability. PMID- 8205655 TI - Exhaled nitric oxide as a marker for organic nitrate tolerance. AB - BACKGROUND: This study was designed to demonstrate the development of biochemical tolerance to organic nitrates by measuring levels of exhaled gaseous nitric oxide (NO) in lambs given intravenous (IV) nitroglycerin or sodium nitroprusside. METHODS AND RESULTS: IV injections of nitroglycerin or sodium nitroprusside produced dose-dependent and sustained increases in the exhaled levels of nitric oxide measured by chemiluminescence in awake lambs with tracheostomies. After a 6 hour IV infusion of 25 micrograms.kg-1.min-1 nitroglycerin, peak exhaled NO levels were significantly reduced (-53.6 +/- 4.9%, mean +/- SEM, P < .001) and systemic hypotensive responses were attenuated (-52.6 +/- 5.9%, P < .001) after an IV challenge of nitroglycerin but not sodium nitroprusside. After a subsequent 12-hour nitroglycerin-free period, there was complete recovery of NO excretion in exhaled breath and a return to baseline of systemic hypotensive changes on administration of IV nitroglycerin boluses. For IV sodium nitroprusside challenges, pulmonary NO excretion and systemic hypotensive responses remained constant throughout the study. Challenges with IV nitroglycerin but not sodium nitroprusside during a 12-hour nitroglycerin-free period resulted in delayed biochemical recovery with various exhaled NO levels and systemic hypotensive responses to challenges with IV nitroglycerin. CONCLUSIONS: Measurements of exhaled NO provide in vivo, noninvasive evidence for the development of biochemical tolerance to nitroglycerin. There was reduced NO release into exhaled gas from the pulmonary vasculature concomitant with evidence of tolerance to nitroglycerin vasodilation in the systemic circulation. PMID- 8205656 TI - Electrophysiological laboratory, electrophysiologist-implanted, nonthoracotomy implantable cardioverter/defibrillators. AB - BACKGROUND: Implantable cardioverter/defibrillators (ICDs) have conventionally been implanted in the operating room by surgeons. However, technological developments have reduced size and increased simplicity, bringing the procedure into the realm of the electrophysiologist. The purpose of this study was to evaluate the safety and efficacy of implantation of the entire ICD system by electrophysiologists in an electrophysiology laboratory. METHODS AND RESULTS: Between July 1993 and February 1994, 23 patients (21 men; age, 64 +/- 11 years) underwent transvenous ICD implantation by electrophysiologists working alone, entirely in the electrophysiology laboratory. Indications for ICD were sudden death in 10 patients, uncontrolled life-threatening ventricular tachycardia in 12, and syncope with cardiomyopathy and familial sudden death in 1. Seventeen patients had coronary artery disease and a past history of acute myocardial infarction. Four patients had idiopathic dilated cardiomyopathy, 1 had coronary ectasia and poor left ventricular function, and another had poor left ventricular function related to valvular dysfunction. The mean left ventricular ejection fraction was 34 +/- 10% (range, 20% to 50%). General anesthesia was administered in 22 cases, and deep sedation was used in 1 elderly patient. After positioning of transvenous leads and subcutaneous patch/array lead positioning, defibrillation testing was performed. After transvenous and subcutaneous lead tunneling, all generators were placed subcutaneously in an abdominal pocket. The mean total time in the electrophysiology laboratory was 254 +/- 68 minutes (range, 150 to 375 minutes), with 104 +/- 42 minutes for anesthetic and other preparation, 159 +/- 45 minutes for implantation, and 8.7 +/- 5 minutes (range, 3 to 25 minutes) of fluoroscopy required for positioning of transvenous and subcutaneous lead systems. Implant times showed a significant improvement when the first 10 cases (188 +/- 44 minutes) were compared with the last 10 in the series (124 +/- 44 minutes, P < .01). The mean defibrillation threshold was 17 +/ 5 J (range, 5 to 25 J). There were 5 complications (22%): 1 patch-site hematoma, 1 pneumothorax related to subclavian venous puncture, 1 pulmonary embolism, and 2 patients requiring overnight ventilation after hemodynamic deterioration following defibrillation testing. There were no deaths, and there were no infections. The mean time to hospital discharge after the implant was 5.1 +/- 3.5 days. After 11.6 +/- 9 weeks of follow-up, all devices were functioning satisfactorily, all patients had successfully defibrillated at postimplant predischarge checkup with 29 +/- 5 J, and there had been no late complications. CONCLUSIONS: This is the first report to show that nonthoracotomy ICD implantation may be successfully carried out by electrophysiologists working alone in the electrophysiology laboratory, with a high rate of success and few complications, even in high-risk patients. This high rate of success and safety probably relates to the availability of high-quality fluoroscopy and familiarity with electrophysiology laboratory equipment and personnel. PMID- 8205657 TI - Exclusion of atrial thrombus by transesophageal echocardiography does not preclude embolism after cardioversion of atrial fibrillation. A multicenter study. AB - BACKGROUND: Transesophageal echocardiography (TEE) has been used recently to detect atrial thrombi before cardioversion of atrial arrhythmias. It has been assumed that embolic events after cardioversion result from embolism of preexisting atrial thrombi that are accurately detected by TEE. This study examined the clinical and echocardiographic findings in patients with embolism after cardioversion of atrial fibrillation despite exclusion of atrial thrombi by TEE. METHODS AND RESULTS: Clinical and echocardiographic data in 17 patients with embolic events after TEE-guided electrical (n = 16) or pharmacological (n = 1) cardioversion were analyzed. All 17 patients had nonvalvular atrial fibrillation, including four patients with lone atrial fibrillation. TEE before cardioversion showed left atrial spontaneous echo contrast in five patients and did not show atrial thrombus in any patient. Cardioversion resulted in return to sinus rhythm without immediate complication in all patients. Thirteen patients had cerebral embolic events and four patients had peripheral embolism occurring 2 hours to 7 days after cardioversion. None of the patients were therapeutically anticoagulated at the time of embolism. New or increased left atrial spontaneous echo contrast was detected in four of the five patients undergoing repeat TEE after cardioversion including one patient with a new left atrial appendage thrombus. CONCLUSIONS: Embolism may occur after cardioversion of atrial fibrillation in inadequately anticoagulated patients despite apparent exclusion of preexisting atrial thrombus by TEE. These findings suggest de novo atrial thrombosis after cardioversion or imperfect sensitivity of TEE for atrial thrombi and suggest that screening by TEE does not obviate the requirement for anticoagulant therapy at the time of and after cardioversion. A randomized clinical trial is needed to compare conventional anticoagulant management with a TEE-guided strategy including anticoagulation after cardioversion. PMID- 8205658 TI - Incidence and treatment of 'no-reflow' after percutaneous coronary intervention. AB - BACKGROUND: Profound reduction in antegrade epicardial coronary flow with concomitant ischemia is seen occasionally during percutaneous coronary intervention despite the absence of evident vessel dissection, obstruction, or distal vessel embolic cutoff. In a prior small series of cases, this "no-reflow" phenomenon appeared to be promptly reversed by the intra-coronary administration of verapamil. METHODS AND RESULTS: To further understand the prevalence of this syndrome and its responsiveness to the proposed therapy, we reviewed 1919 percutaneous interventions performed between January 1991 and April 1993. During the study period, 39 patients (2.0%) met our criteria for no reflow, 37 of whom were treated with intracoronary nitroglycerin followed by intracoronary verapamil and 2 of whom received intracoronary nitroglycerin alone. An additional 16 patients (0.8%) were given verapamil as part of the management of a flow-limiting dissection or distal embolus (mechanical obstruction). Intracoronary verapamil (50 to 900 micrograms, total dose) improved TIMI flow grade in 89% of no-reflow patients and markedly reduced the number of cineframes between contrast injection and opacification of a selected distal landmark (from 91 +/- 56 to 38 +/- 21 frames, P < .001). By contrast, only 19% of patients with epicardial mechanical obstruction showed improvement in TIMI flow grade after verapamil, with minimal reduction in frames to opacification (from 107 +/- 42 to 101 +/- 69, P = .73). CONCLUSIONS: The no-reflow phenomenon--reduction in distal flow without apparent dissection or distal embolization--occurs in 2% of coronary interventions. It generally responds promptly to intracoronary verapamil administration, suggesting that distal microvascular spasm may be its etiology. PMID- 8205659 TI - Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. AB - BACKGROUND: This study aimed to determine if cholesterol-lowering therapy improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. METHODS AND RESULTS: Nine patients with hypercholesterolemia were studied before and after cholesterol-lowering therapy with pravastatin (an inhibitor of HMG-CoA reductase) for 6 +/- 3 months, which lowered serum cholesterol from 272 +/- 8 to 187 +/- 16 mg/dL (P < .01). Control patients with serum cholesterol of 218 +/- 23 mg/dL also were studied twice in a similar interval (8 +/- 2 months) with no cholesterol-lowering drugs. Acetylcholine (the endothelium-dependent vasodilator) and papaverine and nitrate (endothelium-independent vasodilators) were infused into the study coronary artery. Changes in the diameter of the epicardial coronary artery and coronary blood flow were assessed by quantitative coronary arteriography and an intracoronary Doppler catheter. In patients with hypercholesterolemia, acetylcholine-induced vasoconstriction of the epicardial artery was less (P < .05) and the acetylcholine-induced increases in coronary blood flow were greater (P < .001) after than before pravastatin. In control patients, responses of the epicardial coronary artery and coronary blood flow to acetylcholine did not change over the follow-up period. The vasomotor responses to papaverine or nitrate were similar between the two groups, and no interval changes in their responses were noted in either group. CONCLUSIONS: These results suggest that cholesterol-lowering therapy with pravastatin may improve endothelium-dependent coronary vasomotion, which may possibly contribute to the improvement of myocardial perfusion as well as the regression of coronary atherosclerosis. PMID- 8205660 TI - Coronary atherosclerotic wall thickening and vascular reactivity in humans. Elevated high-density lipoprotein levels ameliorate abnormal vasoconstriction in early atherosclerosis. AB - BACKGROUND: Abnormal vascular reactivity represents a fundamental disturbance in vascular biology with the development of atherosclerosis. Because endothelial vasodilator function plays a pivotal role in controlling vasomotor tone, we hypothesized that atherosclerotic wall thickening might directly interfere with deficient endothelium-mediated dilation and thereby contribute to the abnormal reactivity of atherosclerotic arteries in vivo. METHODS AND RESULTS: In 26 patients without focal stenoses in the left anterior descending coronary artery, acetylcholine (0.036 to 3.6 micrograms/mL) was infused into the artery to evaluate endothelium-mediated vasodilation. Segmental vasomotor responses to acetylcholine were correlated with the local extent of atherosclerotic wall thickening quantitated by intracoronary ultrasound examination. Seventeen of the patients also underwent cold pressor testing to assess the vasoreactivity to sympathetic activation. The response of coronary artery segments to acetylcholine varied from 35% dilation to 52% constriction and demonstrated a segmental pattern, with dilation and constriction observed in different segments of the same artery. The vasomotor response to acetylcholine was closely correlated with the extent of local atherosclerotic wall thickening (r = -.82, P < .0001). Over the entire range of atherosclerotic wall thickening, segments from patients with elevated high-density lipoprotein (HDL) cholesterol serum levels (> 75th percentile) demonstrated a significantly blunted constrictor response to acetylcholine (P < .01 at the maximal acetylcholine concentration) compared with segments from patients with HDL cholesterol < 75th percentile. The degree of constriction or dilation in response to the acetylcholine infusion correlated with the response to cold pressor testing (r = .75, P < .0001). Again, the cold pressor test-induced constrictor response was significantly (P < .05) blunted in segments from patients with elevated HDL cholesterol serum levels compared with those from patients with HDL cholesterol < 75th percentile despite equal degrees of atherosclerotic wall thickening. CONCLUSIONS: Coronary vasomotor responses to the endothelium-dependent dilator acetylcholine and to sympathetic stimulation by cold pressor test correlate with local atherosclerotic wall thickening. Thus, the degree of abnormal local vascular reactivity is closely related to the extent of atherosclerotic "plaque load" in human epicardial arteries in vivo. Elevated HDL cholesterol serum levels ameliorate abnormal vasoconstriction at any given extent of atherosclerotic wall thickening, suggesting that HDL cholesterol exerts a beneficial effect on abnormal vascular reactivity, a fundamental functional disturbance associated with coronary atherosclerosis. PMID- 8205661 TI - High-density lipoprotein cholesterol and premature coronary heart disease in urban Japanese men. AB - BACKGROUND: The objective of this study was to examine the relation of high density lipoprotein cholesterol (HDL-C) to coronary heart disease in Japanese men whose serum total cholesterol is low by Western standards. METHODS AND RESULTS: A prospective, observational study based on 7.7 years of follow-up for incidence of coronary heart disease and stroke was conducted. The subjects were 6408 middle aged male workers aged 40 to 59 years at baseline in urban companies in Osaka, Japan, whose mean serum total cholesterol was 5.10 mmol/L. Mean HDL-C adjusted for age, total cholesterol, systolic blood pressure, alcohol intake, cigarette smoking, and body mass index was 1.27 to 1.28 mmol/L for men who developed coronary heart disease (n = 46) or definite myocardial infarction (n = 21) compared with 1.46 mmol/L for those free of cardiovascular disease (n = 6256; difference, P < .01). There was no significant difference in mean HDL-C between stroke cases (n = 33) and those free of cardiovascular disease. The incidence rates of coronary heart disease and definite myocardial infarction, adjusted for the other risk factors, were three to four times higher in the lowest HDL-C quartile (< 1.24 mmol/L) than the highest quartile (> or = 1.66 mmol/L), and there was a significant dose response for definite myocardial infarction. Serum total cholesterol was positively and significantly associated with coronary heart disease incidence. Furthermore, the inverse association for HDL-C was apparent among men with total cholesterol < 5.69 mmol/L (mean total cholesterol, 4.76 mmol/L) and men with total cholesterol > or = 5.69 mmol/L (mean total cholesterol, 6.26 mmol/L). CONCLUSIONS: Coronary heart disease incidence is inversely related to HDL-C in urban Japanese middle-aged men, whose mean total cholesterol (5.10 mmol/L) is relatively low. PMID- 8205662 TI - Physical activity and 23-year incidence of coronary heart disease morbidity and mortality among middle-aged men. The Honolulu Heart Program. AB - BACKGROUND: The purpose of the study was to examine the association between physical activity and 23-year incidence of coronary heart disease morbidity and mortality. This cohort study continues to follow 8006 Japanese-American men who were 45 to 68 years of age and living on Oahu, Hawaii, in 1965, for the development of coronary heart disease morbidity and mortality. METHODS AND RESULTS: The Framingham physical activity index was calculated by summing the product of average hours spent at each activity level and a weighting factor based on oxygen consumption. Study subjects were divided into tertiles of physical activity index at baseline. Relative risks and 95% confidence intervals (CI) for incidence of coronary heart disease morbidity and mortality were obtained using the Cox model. After age adjustment and using the lowest physical activity index tertile as a reference group, the relative risk for coronary heart disease incidence for the highest tertile of physical activity was 0.83 (CI, 0.70 to 0.99). After adjusting for age, hypertension, smoking, alcohol intake, diabetes, cholesterol, and body mass index, the relative risk was 0.95 and CI included 1 (CI, 0.80 to 1.14). For coronary heart disease mortality, the age adjusted relative risk was 0.74 (CI, 0.56 to 0.97) and 0.85 (CI, 0.65 to 1.13) after risk factor adjustment. CONCLUSIONS: The results suggest that the impact of physical activity index on coronary heart disease is mediated through its effects on hypertension, diabetes, cholesterol, and body mass index. These findings support the hypothesis that physical activity is inversely associated with coronary heart disease morbidity and mortality and suggest that physical activity interventions in middle-aged men, by improving cardiovascular risk factor levels, may have significant public health implications in the prevention of coronary heart disease. PMID- 8205663 TI - Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. AB - BACKGROUND: Estrogen replacement therapy has been associated with a reduction in cardiovascular events in postmenopausal women. One of the mechanisms responsible may be a beneficial effect of estrogen on coronary vascular function. We therefore studied the short-term effects of estrogen on coronary artery dimensions and microvascular resistance in postmenopausal women. METHODS AND RESULTS: Twenty postmenopausal women 61 +/- 7 years old participated in this study. Seven had angiographic evidence of atherosclerosis of the left coronary artery. Coronary artery diameters were measured by quantitative coronary angiography. Blood flow velocity was measured with a Doppler wire placed in a proximal left coronary artery segment. Left coronary artery infusions of acetylcholine (range, 10(-8) to 10(-5) mol/L estimated delivered concentrations) and of adenosine (n = 18) and sodium nitroprusside (n = 10) were performed before and during concomitant continuous intracoronary infusion of 17 beta-estradiol to test endothelium-dependent and independent vasodilation, respectively. Intracoronary infusion of estradiol increased coronary sinus estradiol levels from postmenopausal (16 +/- 11 pg/mL) to premenopausal (282 +/- 121 pg/mL) levels. Estradiol did not affect basal coronary artery diameter, blood flow, or resistance. Epicardial coronary artery constriction induced by acetylcholine infusion in the control study (maximum, 10 +/- 15% from baseline) was prevented during repeat acetylcholine infusion with concomitant estradiol administration (P < .001). Estradiol potentiated the vasodilator coronary microvascular response to acetylcholine as manifest by significantly greater coronary flow (P < .001) and lower coronary resistance (P < .02). The reduction in coronary resistance from baseline in response to acetylcholine was significantly potentiated by estradiol (P = .01), with a mean decrease in coronary vascular resistance during acetylcholine infusion of 20 +/- 38% before and 35 +/- 33% during concomitant estradiol administration. The effect of estradiol on coronary dynamics was similar in women with and women without angiographically apparent left coronary artery atherosclerosis and was most prominent in women with the most impaired responses to acetylcholine at both the epicardial (r = -.72, P < .001) and microvascular (r = -.59, P = .006) coronary artery levels. In contrast, estradiol did not affect the coronary epicardial or microvascular vasodilator responses to adenosine or sodium nitroprusside. CONCLUSIONS: Physiological levels of 17 beta estradiol acutely and selectively potentiate endothelium-dependent vasodilation in both large coronary conductance arteries and coronary microvasuclar resistance arteries of postmenopausal women. This effect may contribute to the reduction in cardiovascular events observed with estrogen replacement therapy. PMID- 8205664 TI - Predicting recovery of severe regional ventricular dysfunction. Comparison of resting scintigraphy with 201Tl and 99mTc-sestamibi. AB - BACKGROUND: Regional 201Tl activity after resting injection, imaged early and after redistribution, reflects viable myocardium and can predict improved isotope uptake as well as regional and global ventricular function after revascularization. 99mTc-sestamibi, a perfusion tracer with favorable imaging characteristics, has distinct kinetics compared with 201Tl, demonstrating minimal redistribution; this property may give 201Tl an advantage for detecting viable myocardium, particularly in segments with resting hypoperfusion. The purpose of this study was to compare regional activities of 201Tl and 99mTc-sestamibi after resting injections in patients with coronary artery disease and regional or global left ventricular dysfunction and to assess their comparative abilities for predicting recovery of severe regional ventricular dysfunction after revascularization. METHODS AND RESULTS: Qualitative and quantitative comparisons of rest and redistribution 201Tl activity and sestamibi activity 1 hour after rest injection were performed in 31 patients with coronary artery disease and left ventricular dysfunction. Quantitative analysis of three short-axis tomograms per patient was performed by use of circumferential profiles that allowed analysis of 12 segments per patient. Two-dimensional echocardiography was used to assess wall motion and thickening in segments corresponding to the single photon emission computed tomography data. Concordance between regional 201Tl activity at redistribution imaging and regional sestamibi activity by semiquantitative visual analysis demonstrated concordant regional activity in 87% of segments; among discordant segments, no significant skew was seen, indicating enhanced uptake of one agent over the other. Quantitative analysis for all segments showed significant correlation (r = .86, P < .001) between quantitative regional 201Tl redistribution activity and 1-hour post-rest injection sestamibi activity in individual segments. Eighteen of these patients were revascularized, and echocardiography was repeated 20 +/- 16 days later; segments exhibiting significant regional ventricular dysfunction before revascularization were classified as having reversible or irreversible dysfunction on the basis of the change in wall motion and thickening. 201Tl and sestamibi regional activities were similar in those segments with reversible (72 +/- 11% [percent of peak activity] versus 75 +/- 9%, respectively, P = NS) as well as irreversible ventricular dysfunction (51 +/- 11% versus 50 +/- 8%, P = NS). Positive (75% versus 80% for 201Tl and sestamibi, respectively) and negative (92% versus 96%, respectively) predictive values for recovery of regional ventricular dysfunction after revascularization were similar for the two agents. CONCLUSIONS: In patients with coronary artery disease and left ventricular dysfunction, quantified sestamibi activity 1 hour after rest injection parallels redistribution 201Tl activity after a resting injection, suggesting that uptake and subsequent handling of sestamibi are more complex than can be explained by a pure flow tracer with no redistribution. Quantitative analysis of regional activities of both 201Tl and sestamibi after resting injections can differentiate viable from nonviable myocardium, and the two agents comparably predict reversibility of significant regional wall motion abnormalities after revascularization in such patients to a similar degree. PMID- 8205665 TI - Microvascular integrity indicates myocellular viability in patients with recent myocardial infarction. New insights using myocardial contrast echocardiography. AB - BACKGROUND: Patency of the infarct-related artery (IRA) after acute myocardial infarction (AMI) may not reflect the magnitude of tissue perfusion. In animal models of AMI, myocardial cellular necrosis has been associated with extensive capillary damage. Because myocardial contrast echocardiography (MCE) can define the spatial distribution of microvascular perfusion, we hypothesized that it could be used in patients after recent AMI to distinguish myocardial regions that have an intact microvasculature and thus are viable from those without an intact microvasculature and thus are not viable. METHODS AND RESULTS: One hundred five patients with a recent AMI (range, 1 day to 4 weeks; median, 8 days) who were undergoing cardiac catheterization were included in the study. Two-dimensional echocardiography was performed at baseline and repeated 1 month later to assess regional function within the infarct zone (scores of 1 to 5 indicating normal to dyskinetic segments, respectively). MCE was performed in the cardiac catheterization laboratory to assess microvascular perfusion within the infarct bed. A contrast score index was derived by assigning scores to individual segments within the infarct zone (0, 0.5, and 1 denoting no, intermediate, and homogeneous contrast effect, respectively) and deriving the average score within the infarct bed. Revascularization was performed as clinically indicated. Although the baseline wall motion score and the contrast score index were similar in the 90 patients with a patent IRA and the 15 patients with an occluded IRA (median +/- 1 interquartile range, 3 +/- 1 versus 3.5 +/- 1; P = .41), wall motion score 1 month later was significantly better in those with open IRAs compared with those with closed IRAs (2 +/- 2 versus 3 +/- 2, P = .05). In the 90 patients with an open IRA, a strong correlation was noted between wall motion score 1 month later and the contrast score index (rho = -.64, P < .001). On multivariate analysis, the best correlate of the 1-month wall motion score was the contrast score index. CONCLUSIONS: In patients studied in the cardiac catheterization laboratory between 1 day and 4 weeks after AMI, an intact microvasculature as identified by MCE indicates myocardial regions that improve function 1 month later. This study demonstrates that microvascular patency is closely associated with myocardial cellular viability after AMI in humans. PMID- 8205667 TI - Compensatory carotid artery dilatation in early atherosclerosis. AB - BACKGROUND: From pathological studies of coronary arteries, it has been recognized that progressive plaque development may be compensated for by an increase of the arterial diameter. However, the dynamics of this process have not been investigated, and it is not known whether compensatory dilatation is a general pathomechanism in human arteries. METHODS AND RESULTS: Using a high resolution duplex scanner and subsequent three-dimensional plaque reconstruction, we prospectively studied the effect of carotid plaque development on the vascular geometry in 32 patients at 6- to 12-month intervals. Plaque progression in 41% (n = 26) of studies was associated with an increase of the vessel diameter between 0.4 and 1.2 mm in 76% (n = 20). Among 36 unchanged plaque developments, enlargement of the arterial diameter was assessed in only 28% (n = 10) (P < .001). CONCLUSIONS: Our data suggest that increasing plaque volume is significantly associated with enlargement of carotid artery segments, which compensates for arterial narrowing in early stages of the disease. PMID- 8205666 TI - Focal compensatory enlargement of human arteries in response to progressive atherosclerosis. In vivo documentation using intravascular ultrasound. AB - BACKGROUND: Previous postmortem studies have demonstrated compensatory enlargement of atherosclerotic arteries in animal models and patients. Conclusions regarding these changes were drawn based on a comparison of the dimensions of diseased arteries in one group of subjects with the dimensions of normal arteries in another group. This method admits potential confounding variables, such as demographics and other disease states, which might also have an impact on arterial size. METHODS AND RESULTS: Using intravascular ultrasound, we studied a total of 62 paired, adjacent normal and diseased sites in the superficial femoral arteries of 20 patients undergoing peripheral vascular interventions. Morphological assessment was performed using a computer-based image analysis system. Measurements were made of the cross-sectional area of the arterial lumen, the atherosclerotic plaque, and the outer border of the artery. These dimensions were then compared to determine the effects of progressive atherosclerosis on arterial morphology. Luminal cross-sectional area decreased from 21.1 +/- 2.2 mm2 in normal segments to 16.7 +/- 0.8 mm2 (P = .0001) in adjacent atherosclerotic segments. Similarly, minimal luminal diameter decreased from 5.7 +/- 0.2 to 5.0 +/- 0.1 mm2, and maximal luminal diameter decreased from 6.2 +/- 0.2 to 5.7 +/- 0.2 mm2. At these same sites, total arterial area was 32.9 +/- 1.6 and 37.9 +/- 1.9 mm2 (P = .0001) in normal and diseased segments, respectively. Minimal and maximal arterial diameters demonstrated similar increases (7.3 +/- 0.2 to 7.7 +/- 0.2 mm2 [P = .0015] and 7.6 +/- 0.2 to 8.3 +/- 0.2 mm2 [P = .0001], respectively). Regression analysis disclosed correlation of the cross-sectional area of plaque to the total arterial area (R = .70, P = .0001). CONCLUSIONS: Human arteries enlarge in response to progressive atherosclerosis. This compensatory mechanism results in an increase in arterial size that is proportionate to the cross-sectional area of plaque that has accumulated in the vessel. Intravascular ultrasound demonstrates that this process is focal compensatory enlargement at discrete sites of atherosclerotic narrowing immediately adjacent to more normal areas in which arterial size is smaller. PMID- 8205668 TI - Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy. AB - BACKGROUND: Enteroviral RNA sequences have been demonstrated in the myocardium of patients with myocarditis or dilated cardiomyopathy from presentation to end stage disease. The prognosis of heart muscle disease has not previously been evaluated in relation to the detection of enterovirus in myocardial biopsy tissue. METHODS AND RESULTS: We studied 123 consecutive patients with heart muscle disease prospectively. Multiple endomyocardial biopsy samples taken from all patients during diagnostic cardiac catheterization were classified histologically and were examined for enteroviral RNA by use of an enterovirus group-specific hybridization probe. Three enterovirus-negative patients with cardiac amyloidosis were excluded from subsequent analysis. Enteroviral RNA sequences were detectable in 41 (34%) of the remaining 120 patients (group A), while 79 (66%) had no virus detected (group B). The groups did not differ significantly in age, sex, symptomatic presentation, or hemodynamic characteristics; duration of symptoms was significantly shorter in group A (7.8 +/- 9.6 versus 14.9 +/- 19.0 months, P < .05). At follow-up (mean, 25 months; range, 11 to 50 months), patients from group A had an increased mortality compared with those in group B (25% versus 4%, respectively; P = .02). Mortality was also statistically greater in patients with symptomatic cardiac failure (P = .02), those with elevated left ventricular end-diastolic pressures (P = .03), and those in New York Heart Association functional classes III and IV (P = .05). Multivariate regression analysis, however, showed that only the presence of enterovirus RNA and symptomatic heart failure were of independent prognostic value. CONCLUSIONS: These data demonstrate that the detection of enterovirus RNA in the myocardium of patients with heart muscle disease at the time of initial investigation is associated with an adverse prognosis and that the presence of enterovirus RNA is an independent predictor of clinical outcome. PMID- 8205669 TI - Platelet aggregation and HDL cholesterol are predictive of acute coronary events in heart transplant recipients. AB - BACKGROUND: Sudden death (SD) and acute myocardial infarction (AMI) are the main complications limiting long-term survival after heart transplantation (HT). They are unpredictable and, at present, unpreventable. Platelet aggregation (PA) has recently emerged as a significant prognostic indicator in nontransplanted coronary disease patients. The main purpose of the present study was to evaluate to what extent PA could predict SD and AMI in long-term survivors of HT independently of serum lipid levels. METHODS AND RESULTS: We studied 207 patients. All received triple immunosuppressive therapy. During follow-up, the incidence of SD and AMI was determined, and the independent role of PA as predictor was evaluated with other usual risk factors by a Cox multivariate regression model. There were 11 SDs and 14 AMIs after an average follow-up of 642 days, giving an average incidence rate of 7.3 events per year per hundred patients. By univariate analysis, the most potent predictors were ADP-induced platelet aggregation (positive association) and total cholesterol (negative association). Age and length of time since transplant were not predictors. By multivariate analysis, only the secondary wave of ADP-induced platelet aggregation (P = .001) and high-density lipoprotein cholesterol (P = .03) were independent predictors. The relative risk of SD or AMI based on a comparison between patients with high (> 36%) or low (< 36%) ADP-induced platelet aggregation was 4.3 (95% confidence interval, 1.9 to 9.5, P = .0001). CONCLUSIONS: This study provides the first demonstration of an association between increased platelet aggregation and subsequent SD or AMI in HT recipients. It suggests that platelets and thrombosis also are implicated in the pathogenesis of AMI and SD in HT recipients. Identification of a safe and effective antiplatelet therapy should be actively pursued. PMID- 8205670 TI - Potentiation of isosorbide dinitrate effects with N-acetylcysteine in patients with chronic heart failure. AB - BACKGROUND: Supply of sulfhydryl groups with the administration of N acetylcysteine (NAC) has been reported to reverse tolerance to nitroglycerin but not to isosorbide dinitrate (ISDN). Lack of interaction between NAC and ISDN was suggested as an explanation for these findings. The present study was therefore designed to further evaluate this hypothesis. For this purpose, we compared the hemodynamic and hormonal effects of ISDN when given alone and in combination with NAC. METHODS AND RESULTS: We performed a randomized, cross-over design evaluation of the hemodynamic and hormonal effects of ISDN and ISDN + NAC in 14 patients with chronic congestive heart failure due to left ventricular systolic dysfunction. The findings of this study demonstrated a substantial NAC-mediated potentiation of ISDN effect on mean right atrial pressure (-11 +/- 21% versus -38 +/- 27%, -17 +/- 20% versus -34 +/- 27%, and -7 +/- 20% versus -25 +/- 26% at 2, 3, and 4 hours, respectively; all P < .05), mean pulmonary artery wedge pressure (-18 +/- 16% versus -33 +/- 14%, -15 +/- 25% versus -33 +/- 19%, -14 +/- 22% versus -25 +/- 22%, and -16 +/- 16% versus -26 +/- 16% at 2, 3, 4, and 5 hours, respectively; all P < .05), mean pulmonary artery pressure (-8 +/- 11% versus -20 +/- 15% at 3 hours, P < .05), and cardiac output (an increase of 2 +/- 16% versus 25 +/- 20% at 4 hours, P < .05). Although there were no significant changes in serum catecholamine levels and plasma renin concentration with both regimens, ISDN + NAC resulted in a greater fall in plasma levels of atrial natriuretic peptide (296 +/- 251 pg/mL after ISDN versus 202 +/- 118 pg/mL after ISDN + NAC, P < .05). CONCLUSIONS: The results of this study provide strong evidence for the existence of an interaction between thiols and ISDN and further support the role of sulfhydryl groups in the activation and therapeutic action of organic nitrates. The discrepancy between the results of this study demonstrating NAC induced potentiation of ISDN effects and a previous study showing failure to reverse ISDN tolerance with NAC may suggest that ISDN-NAC interaction requires normal intracellular levels of sulfhydryl groups and does not occur after intracellular sulfhydryl group depletion. PMID- 8205671 TI - Diurnal variation in blood pressure in patients with biventricular assist devices and retained, nonpumping native hearts. AB - BACKGROUND: Studies indicate that centrally mediated rhythms in sympathetic tone play a prominent role in diurnal cardiovascular variability. Recent evidence from heart transplant recipients, in whom blood pressure does not decline during sleep despite normal variability in plasma norepinephrine, however, suggests that afferent cardiac nervous traffic is necessary for the generation of diurnal variability. This implies that in the presence of an innervated heart excluded from the systemic circulation, blood pressure would still decrease during sleep. To assess this hypothesis, we studied 24-hour blood pressure, heart rate, and neuroendocrine variability in patients with biventricular assist devices in whom the retained native hearts had ceased to pump. METHODS AND RESULTS: Eight patients were free of medication and were studied every 3 hours. Pump rates and output were kept constant throughout the study. Blood pressure showed a significant decline during sleep, as did norepinephrine and epinephrine (all P < .05). Atrial natriuretic factor showed a significant increase around midnight (P < .01). Significantly elevated levels were found for all hormones studied except for aldosterone and endothelin. CONCLUSIONS: Our results suggest that diurnal variations in cardiac function or in catecholamine levels (indicative of sympathetic activity) as found in cardiac transplant recipients alone are not responsible or sufficient for producing a nocturnal drop in blood pressure. The presence of an innervated heart appears crucial in this respect. This could be of importance for the understanding of circadian cardiovascular pathophysiology. PMID- 8205672 TI - Central and peripheral limitations to upright exercise in untrained cardiac transplant recipients. AB - BACKGROUND: Functional capacity and quality of life are subjectively improved after cardiac transplantation. However, the objective improvement in exercise tolerance after transplantation has been disappointing. The extent to which allograft diastolic dysfunction contributes to this exercise intolerance has not been defined. METHODS AND RESULTS: Thirty cardiac transplant recipients between 3 and 16 months after transplantation and 30 age-matched normal control subjects underwent maximal symptom-limited graded upright bicycle exercise testing with simultaneous radionuclide angiography, invasive hemodynamic monitoring, and breath-by-breath gas analysis. Mean blood pressure was higher in the transplant group at supine rest (112.1 versus 97.7 mm Hg), normalized with upright posture, and became lower than normal at peak exercise (121.1 versus 133.2 mm Hg). Systolic function as measured by ejection fraction was normal in both groups. However, the cardiac transplant recipients had significantly lower exercise tolerance, achieving a mean maximal work rate of 390 kilopond-meters per minute (kpm/min), compared with 825 kpm/min in the normal subjects. Peak oxygen consumption was 12.3 mL.min-1.kg-1 in the transplant group, 46% lower than the normal group's value of 22.9 mL.min-1.kg-1. The transplant patients had a resting tachycardia (94 beats per minute) and a 79% reduction in exercise heart rate reserve compared with normal. Despite this chronotropic incompetence, stroke index response to exercise was consistently lower after transplantation, accounting for a 41% reduction in cardiac index at maximal exercise. The lower stroke index was accompanied by a 32% lower end-diastolic volume index at rest and a 14% lower end-diastolic volume index at peak exercise. Despite the smaller ventricular volumes after transplantation, pulmonary capillary wedge pressure was 35% higher than normal at supine rest and 50% higher at maximal exercise. Right atrial and mean pulmonary arterial pressures were similarly elevated. The ratio of pulmonary capillary wedge pressure to end-diastolic volume index was significantly higher during the postural change and exercise, suggesting allograft diastolic dysfunction. Arteriovenous oxygen difference was similar between groups at rest and with submaximal exercise but was 24% lower at maximal exercise in the transplant group, suggesting an abnormality in peripheral oxygen uptake or utilization. CONCLUSIONS: Exercise tolerance is severely limited during the first 16 months after cardiac transplantation despite preservation of allograft left ventricular systolic function. This intolerance is due to an inadequate cardiac index response from a combination of chronotropic incompetence and diastolic dysfunction limiting the appropriate compensatory use of the Starling mechanism. In addition, there is a peripheral abnormality in oxygen transport or utilization that may partially reflect the effects of deconditioning. PMID- 8205673 TI - Intracoronary angiotensin-converting enzyme inhibition improves diastolic function in patients with hypertensive left ventricular hypertrophy. AB - BACKGROUND: There is increasing recognition of myocardial angiotensin-converting enzyme, which is induced with the development of left ventricular hypertrophy (LVH). The potential physiological significance of subsequent increased angiotensin I to II conversion in the presence of LVH is unclear but has been postulated to cause abnormal Ca2+ handling and secondary diastolic dysfunction. Accordingly, we hypothesized that acute angiotensin-converting enzyme inhibition would result in decreased production of angiotensin II and improved active (Ca(2+)-dependent) relaxation in patients with hypertensive LVH. METHODS AND RESULTS: Intracoronary (IC) enalaprilat was administered to 25 patients with and without LVH secondary to essential hypertension. Indexes of diastolic and systolic LV function were determined from pressure (micromanometer)-volume (conductance) analysis at steady state and with occlusion of the inferior vena cava. Patients were divided into those receiving high- (5.0 mg, n = 15) and low dose (1.5 mg, n = 10) IC enalaprilat during a 30-minute infusion at 1 mL/min. The high-dose patients were further divided along the median normalized LV wall thickness of 0.671 cm/m2. The time constant of isovolumic relaxation (TauL) was prolonged at baseline in patients receiving high-dose enalaprilat with wall thickness > 0.671 cm/m2 (TauL, 56 +/- 2 versus 44 +/- 2 and 45 +/- 2 milliseconds, respectively, P < .01 by ANOVA) and shortened only in this patient group (TauL, 49 +/- 3 versus 46 +/- 2 and 43 +/- 2 milliseconds, respectively, P < .01 versus baseline and other groups by ANOVA). The improvement in TauL was directly proportional to the degree of LVH (r = .92, P < .001). Although there was a decrease in LV end-diastolic pressure (23 +/- 2 to 15 +/- 1 mm Hg, P < .01) and volume (86 +/- 8 to 67 +/- 9 mL/m2, P < .05) in those patients with a reduction in TauL, this is due to movement down a similar diastolic pressure volume relation with no change in chamber elastic stiffness (0.023 +/- 0.002 to 0.025 +/- 0.004 mL-1, P = NS). CONCLUSIONS: Intracoronary enalaprilat resulted in an improvement in active (Ca(2+)-dependent) relaxation in those patients with more severe hypertensive LVH. The improvement in active relaxation was directly proportional to the severity of LVH. These results support the hypothesis that the cardiac renin-angiotensin system is an important determinant of active diastolic function in hypertensive LVH. PMID- 8205674 TI - Biphasic effects of repeated alcohol intake on 24-hour blood pressure in hypertensive patients. AB - BACKGROUND: The association between alcohol and blood pressure (BP) may be related to the temporal sequencing of alcohol use and BP measurement. We investigated the effects of single and repeated intakes of alcohol on 24-hour BP. METHODS AND RESULTS: Fourteen male habitual drinkers with essential hypertension were placed sequentially on a 4-day control phase: a nonalcoholic drink with the same calories as alcohol was given at dinner (5 PM to 6 PM) and a 7-day drinking phase: alcohol (ethanol, 1 mL/kg) was given at dinner under standardized conditions. Ambulatory BP measurements were performed on day 3 of the control phase and on days 1 and 7 of the alcohol phase. The average 24-hour systolic and diastolic BPs on day 1 were significantly lower than those in the control phase and on day 7. Between 6 PM and midnight, both systolic and diastolic BPs on days 1 and 7 (121 +/- 2/73 +/- 1 and 126 +/- 4/75 +/- 2 mm Hg, respectively) were significantly lower than those in the control phase (139 +/- 4/83 +/- 2 mm Hg). Between midnight and 8 AM (6 to 14 hours after the last drink), both systolic and diastolic BPs on day 7 (138 +/- 4/83 +/- 2 mm Hg) were significantly higher than those in the control phase (131 +/- 4/79 +/- 2 mm Hg) and day 1 (129 +/- 3/77 +/- 1 mm Hg). Between 8 AM and 3 PM, BPs showed no difference among the three phases. CONCLUSIONS: A single intake of alcohol has a depressor effect on BP that lasts for several hours after drinking, while repeated intakes for 7 days have both depressor and pressor effects according to the differences in time intervals after the last drink. This study suggests that the chronic effects of alcohol on BP might be overestimated when based on casual BP measurements alone. PMID- 8205675 TI - Body fat and sympathetic nerve activity in healthy subjects. AB - BACKGROUND: Obesity is associated with an increased incidence of cardiovascular complications, but the underlying mechanism is unknown. In experimental animals, overfeeding is associated with sympathetic activation, and there is evidence that adrenergic mechanisms contribute to cardiovascular complications. METHODS AND RESULTS: We recorded resting postganglionic sympathetic nerve discharge (using intraneural microelectrodes) to skeletal muscle blood vessels in 37 healthy subjects covering a broad spectrum of percent body fat. To assess potential functional consequences of sympathetic nerve discharge, we simultaneously measured calf vascular resistance and energy expenditure. The resting rate of sympathetic nerve discharge to skeletal muscle was directly correlated with body mass index (r = .67, P < .0001) and percent body fat (r = .64, P < .0001). In addition to body fat, muscle sympathetic nerve activity was correlated with age (r = .40, P < .02), plasma insulin concentration (r = .34, P < .04), and plasma lactate concentration (r = .35, P < .04). Together, these four covariates accounted for 58% of the variance of muscle sympathetic nerve activity (P < .0001). The rate of sympathetic nerve discharge to calf blood vessels was directly correlated with calf vascular resistance (r = .40, P < .02) but did not predict energy expenditure (r = .22, P = .19). CONCLUSIONS: In healthy humans, body fat is a major determinant of the resting rate of muscle sympathetic nerve discharge. Overweight-associated sympathetic activation could represent one potential mechanism contributing to the increased incidence of cardiovascular complications in overweight subjects. PMID- 8205676 TI - Efficacy of a single-lead unipolar transvenous defibrillator compared with a system employing an additional coronary sinus electrode. A prospective, randomized study. AB - BACKGROUND: Recent development of a prototype single-lead unipolar transvenous defibrillator offers the possibility of device implantation with the ease of a permanent pacemaker. Lowering defibrillation energy requirements would allow for a further reduction in defibrillator generator size and enhance the feasibility of pacemaker-like placement. However, if achieving a lower defibrillation energy requires placing additional intracardiac leads, the potential advantage of a smaller generator may be offset by the disadvantages of a more complex lead system. The purpose of this study was to compare defibrillation energy requirements of a single-lead unipolar defibrillator with a three-electrode system employing an additional lead in the coronary sinus. METHODS AND RESULTS: Testing of a single-lead unipolar biphasic pulse defibrillation system versus a three-electrode system with an additional coronary sinus lead was performed in prospective, randomized fashion in 15 patients with a history of ventricular tachycardia or fibrillation. Ventricular fibrillation was induced with alternating current, and defibrillation threshold was measured by a pulse given 10 seconds after arrhythmia induction. The mean defibrillation threshold stored energy and mean leading edge voltage did not significantly differ between the two systems (11.3 +/- 5.9 J versus 9.9 +/- 5.2 J and 418 +/- 118 V versus 390 +/- 112 V, respectively; P > .4). Using either defibrillation system, all patients were successfully defibrillated by < 24 J and over half of patients by < 10 J. CONCLUSIONS: A unipolar transvenous biphasic defibrillation system is an effective means of treating ventricular fibrillation. The added complexity of additional leads is not offset by any significant improvement in defibrillation efficacy or energy requirements. Given the simplicity and effectiveness of a single-lead system coupled with a small generator, placement of defibrillation systems may now approach the ease of pacemaker implantation. PMID- 8205677 TI - Mechanism-specific effects of adenosine on atrial tachycardia. AB - BACKGROUND: Recent reports suggest that adenosine, in addition to terminating supraventricular tachycardia involving the atrioventricular (AV) node, may have antiarrhythmic effects on atrial tachycardia. The electrophysiological effects of adenosine on supraventricular tissue include shortening of action potential duration in atrial myocytes mediated by the potassium current, IKACh,Ado; shortening of action potential duration and hyperpolarization in sinus node cells; and anti-adrenergic electrophysiological effects resulting from inhibition of adenylyl cyclase. We therefore hypothesized that the response of atrial tachycardia to adenosine would be mechanism specific, with termination of atrial tachycardia due to sinus node reentry or cAMP-mediated triggered activity, transient suppression of automatic atrial tachycardia, and an absence of antiarrhythmic effect on tachycardia due to intraatrial reentry. METHODS AND RESULTS: Adenosine (mean +/- SD, 143 +/- 54 micrograms/kg IV) was administered to 27 patients (55 +/- 19 years) in atrial tachycardia whose mechanism was confirmed by electrophysiological study. Adenosine terminated sinus node reentrant tachycardia in 6 of 6 patients and terminated atrial tachycardia due to triggered activity in the 1 patient in whom it was identified. Adenosine transiently suppressed automatic atrial tachycardia in 7 of 7 patients and had no effect in 13 patients with intra-atrial reentrant tachycardia, including 8 patients with atrial flutter. CONCLUSIONS: These findings demonstrate that adenosine's effects on atrial tachycardia are mechanism specific and can be used to differentiate between reentrant tachycardia confined to the region of the sinus node or atria and between nonreentrant atrial tachycardia due to either triggered activity or automaticity. PMID- 8205678 TI - Radiofrequency catheter ablation of right atriofascicular (Mahaim) accessory pathways guided by accessory pathway activation potentials. AB - BACKGROUND: Accessory pathways (APs) exhibiting "Mahaim fiber" physiology (antegrade conduction only, long conduction time, and decremental properties) often connect the lateral right atrium to the right bundle branch (right atriofascicular pathways). Potentials from these pathways have not been recorded previously. The purpose of this study was to determine whether AP activation potentials could be recorded from right atriofascicular APs and to determine whether these potentials could be used to localize a site for catheter ablation. METHODS AND RESULTS: Of 26 consecutive patients referred for catheter ablation of an AP producing a preexcited (antidromic) atrioventricular (AV) reentrant tachycardia having a left bundle branch block pattern with short ventriculoatrial and long AV intervals, 23 (88.5%) were found to have a right atriofascicular AP. During antidromic AV reentrant tachycardia, (1) right atrial extrastimuli (that did not penetrant tachycardia, (1) right atrial extrastimuli (that did not penetrate the AV node) advanced the timing of the next QRS complex, indicating that the AP was connected to the right atrium; (2) earliest antegrade ventricular activation was recorded at the apical right ventricular free wall, and (3) ventricular activation was preceded by activation of the distal right bundle branch, indicating a fascicular insertion or a ventricular insertion close to the terminus of the right bundle branch. A single, discrete, high-frequency AP potential was recorded at the lateral, anterolateral, or posterolateral tricuspid annulus in 22 of the 23 patients 63 +/- 12 milliseconds after the local atrial potential and 83 +/- 23 milliseconds before the local ventricular potential during sinus rhythm. The AP potential was also recorded at sites along the right ventricular free wall between the tricuspid annulus and the site of earliest ventricular activation at the apical region. Programmed atrial stimulation and adenosine each produced prolongation of AP conduction time because of an increase in the A-AP interval and Wenckebach block proximal to the AP potential. Radiofrequency current applied at a site recording the AP potential (tricuspid annulus in 19 patients and right ventricular free wall in 3 patients) eliminated AP conduction in all 22 patients. Tachycardia has not recurred in any patient during 18 +/- 13 months of follow-up. AP conduction was absent in all 9 patients who had a follow-up electrophysiological study 3.8 +/- 1.7 months after ablation. CONCLUSIONS: Right atriofascicular APs consist of two components. The proximal component is located at the lateral, anterolateral, or posterolateral tricuspid annulus, does not generate an AP potential recordable by catheter electrodes, and is responsible for the decremental conduction properties. The "distal" component extends from the tricuspid annulus to the distal right bundle branch at the apical right ventricular free wall and generates a large, high-frequency AP potential that accurately identifies a site for ablation. PMID- 8205679 TI - Effects of radiofrequency catheter ablation on regional myocardial blood flow. Possible mechanism for late electrophysiological outcome. AB - BACKGROUND: We postulated that the late electrophysiological effects of radiofrequency (RF) ablation may be related to microvascular injury extending beyond the region of acute coagulation necrosis. METHODS AND RESULTS: Eighteen RF lesions created in the left anterior descending coronary artery (LAD) perfusion bed of seven open chest anesthetized dogs were studied. The ablation electrode and surrounding myocardium were imaged using high-resolution two-dimensional echocardiography at x 4 magnification. After 60 seconds of RF delivery, sonicated albumin microbubbles (mean size, 4.3 microns) were injected into the LAD to measure regional myocardial perfusion, and time-intensity plots were generated from simultaneously acquired two-dimensional echocardiography images. The regions with persistent contrast effect on two-dimensional echocardiography were larger than the pathological lesions (mean cross-sectional area, 48.3 +/- 6.3 versus 19.3 +/- 4.7 mm2, respectively; P < .0001). The mean contrast transit rate in the area corresponding to the pathological lesion was 25 +/- 12% of that in the normal myocardium, but it was also reduced beyond the lesion, being 48 +/- 27% and 82 +/- 28% of normal, respectively, in the 3-mm and 3- to 6-mm circumferential rims surrounding the pathological lesion (P < .05). Electron microscopy performed in two additional dogs with similar lesions demonstrated the presence of ultrastructural damage to the microvascular endothelium well beyond the pathological lesion edge. CONCLUSIONS: RF catheter ablation not only results in a marked reduction in blood flow within the acute pathological lesion but also causes reduced flow beyond the borders of the acute lesion because of microvascular endothelial cell injury. The progression or resolution of tissue injury within the region beyond the border of the pathological lesion may explain the late electrophysiological effects of RF ablation. PMID- 8205680 TI - Pregnancy in cyanotic congenital heart disease. Outcome of mother and fetus. AB - In a series of 416 women with congenital heart disease seen in the Royal Brompton National Heart and Lung Hospital, London, and the Hospital Giovanni Bosco, Torino, Italy, there were 822 pregnancies. The outcomes of 96 pregnancies in 44 patients with cyanotic congenital heart disease were studied. Patients with the Eisenmenger reaction were excluded. Patients were divided arbitrarily into groups according to the type of maternal congenital cardiac anomaly, and factors influencing maternal and fetal outcome were evaluated. The incidence of maternal cardiovascular complications was high (32%), with one death from endocarditis 2 months after delivery. Forty-one (43%) of 96 pregnancies resulted in a live birth; 15 (37%) were premature. Mean weight of full-term infants was 2575 g. Univariate analysis suggested that maternal disease, Ability Index, hemoglobin, and arterial oxygen saturation before the pregnancy were factors that discriminated between successful and unsuccessful fetal outcome, with hemoglobin and arterial oxygen saturation being the most important predictors. Women with cyanotic congenital heart disease can go through pregnancy with a low risk to themselves, with frequent treatable complications, but there is a high incidence of miscarriage, premature births, and low birth weights. An incidence of congenital heart disease in the fetus of 4.9% (2 of 41 live births) is higher than that found in the normal population. PMID- 8205681 TI - Balloon angioplasty with stent implantation in experimental coarctation of the aorta. AB - BACKGROUND: Balloon angioplasty of coarctation of the aorta is an effective method of treatment but is complicated by tearing of the aortic intima, formation of aneurysms, and restenosis. Stent placement at the time of balloon dilation could prevent restenosis and could also prevent progression of intimal tears to aneurysms. The purpose of this study was to evaluate the feasibility of balloon dilation and implantation of balloon-expandable stents in an experimental model of coarctation and to examine the effect of stent placement at the site of surgically created stenosis. METHODS AND RESULTS: Coarctation of the aorta was surgically produced in 11 juvenile swine. Simultaneous coarctation angioplasty and stent implantation was performed in 10 animals 34 +/- 7.8 days after surgery. Repeat catheterization was performed 59 +/- 6 days after stent implantation. Five animals underwent reexpansion of stents with subsequent follow-up catheterization. Aortic specimens were examined by light microscopy and scanning electron microscopy. Coarctation angioplasty with stent implantation was successful in all, with an increase in coarctation diameter from 46 +/- 8.5% to 90 +/- 12.2% of proximal aortic diameter (P = .0001). Systolic pressure gradient decreased from 32 +/- 19.8 to 0.5 +/- 2.8 mm Hg (P < .001). All stents were patent at follow-up catheterization, with no evidence of intraluminal thrombosis. Reexpansion in five animals increased the stent diameter from a mean of 77.4 +/- 12.1% to 93 +/- 11.0% of proximal aortic diameter (P = .02). Gross examination of aortic specimens demonstrated formation of neointima over the stent wherever the stent struts were in contact with the aortic wall. The stent occupied a subintimal position and produced minimal compression of the underlying media. Medial compression was noted immediately beneath stent struts, but there was no evidence of intimal or medial dissection. CONCLUSIONS: Balloon angioplasty with simultaneous implantation of balloon-expandable stents is effective in relieving aortic obstruction in experimental coarctation. Reexpansion of the rigid stent can be performed in an area of surgical aortotomy and coarctation without significant intimal or medial injury. Stent implantation may be useful in preventing restenosis and aneurysm formation after angioplasty of coarctation. PMID- 8205682 TI - Usefulness of transesophageal echocardiography for diagnosis of infected transvenous permanent pacemakers. AB - BACKGROUND: Transesophageal echocardiography is superior to transthoracic echocardiography in detecting left-sided valvular vegetations. There are no data on the value of transesophageal echocardiography in the diagnosis of infected transvenous permanent pacemakers. METHODS AND RESULTS: Transthoracic and transesophageal echocardiography was performed in 10 patients for whom there was clinical suspicion of infected permanent transvenous pacemakers. Transthoracic echocardiography detected pacemaker lead vegetations in 2 patients, whereas transesophageal echocardiography visualized pacemaker lead vegetations in 7 patients. Surgical confirmation was obtained in 6 of these 7 patients. Most patients had more than one pacemaker electrode in place. Local complications at the generator pocket were present in 6 patients. Staphylococcus was the predominant causative organism. CONCLUSIONS: Transesophageal echocardiography is superior to transthoracic echocardiography in the detection of pacemaker lead vegetations. PMID- 8205683 TI - Noninvasive method for determination of arterial compliance using Doppler echocardiography and subclavian pulse tracings. Validation and clinical application of a physiological model of the circulation. AB - BACKGROUND: The Poiseuillian model of the arterial system currently applied in clinical physiology does not explain how arterial pressure is maintained during diastole after cessation of pulsatile aortic inflow. Arterial pressure-flow relations can be more accurately described by models that incorporate arterial viscoelastic properties such as arterial compliance. Continuous pressure and flow measurements are needed to evaluate these properties. Since the techniques used to date to acquire such data have been invasive, physiological models of the circulation that incorporate these properties have not been widely applied in the clinical setting. The purpose of this study was (1) to validate noninvasive methods for continuous measurement of central arterial pressure and flow and (2) to determine normal reference values for arterial compliance using physiological models of the circulation applied to the noninvasively acquired pressure and flow data. METHODS AND RESULTS: Simultaneously acquired invasive and noninvasive aortic pressures (30 patients), flows (8 patients), and arterial mechanical properties (8 patients) were compared. Pressure was measured by high-fidelity catheter aortic micromanometer (invasive) and calibrated subclavian pulse tracing (noninvasive). Aortic inflow was determined from thermodilution-calibrated electromagnetic flow velocity data (invasive) and echo-Doppler data (noninvasive). Arterial compliance was determined for two- and three-element windkessel models of the circulation using the area method and an iterative procedure, respectively. Once validated, the noninvasive methodology was used to determine normal compliance values for a reference population of 70 subjects (age range, 20 to 81 years) with normal 24-hour ambulatory blood pressures and without Doppler-echocardiographic evidence for structural heart disease. The limits of agreement between invasive and noninvasive pressure data, compared at 10% intervals during ejection and nonejection, were narrow over a wide range of pressures, with no significant differences between methods. Invasive and noninvasive instantaneous aortic inflow values differed slightly but significantly at the start of ejection (P < .05), but during the latter 90% of ejection, values for the two methods were similar, with narrow limits of agreement. Total vascular resistance and arterial compliance values derived from invasive and noninvasive data were similar. Arterial compliance values for the normal population using the two-element model (C2E) ranged from 0.74 to 2.44 cm3/mm Hg (mean, 1.57 +/- 0.38 cm3/mm Hg), with a beat-to-beat variability of 5.2 +/- 3.9%. C2E decreased with increasing age (r = -.73, P < .001) and tended to be higher in men (1.67 +/- 0.41 cm3/mm Hg) than in women (1.51 +/- 0.35 cm3/mm Hg, P = .07). Compliance values for the three-element model (C3E) were predictably smaller than for the two-element model (mean, 1.23 +/- 0.30; range, 0.59 to 2.16 cm3/mm Hg, P < .001 versus C2E) but correlated with C2E values (r = .81, P < .001) and were also inversely related to age (r = -.56, P < .001). Ridge regression and principal component analyses both showed the compliance value to be a composite function whose variation could be best predicted by consideration of simultaneous values for five major hemodynamic determinants: heart rate, mean flow, mean aortic pressure, minimal diastolic pressure, and end-systolic pressure. Multivariate analysis revealed age and sex to be independent predictors of compliance (P < .01 for both). There were no differences in compliance between black and white subjects. CONCLUSIONS: Noninvasive methods can be used to acquire the hemodynamic data necessary for clinical application of physiological models of the circulation that incorporate arterial viscoelastic properties such as arterial compliance. The strong inverse linear relation between model-based compliance estimates and age mandates incorporation of this demographic parameter in PMID- 8205684 TI - Improving detection of coronary morphological features from digital angiograms. Effect of stenosis-stabilized display. AB - BACKGROUND: We have developed a digital display method that stabilizes the motion of a stenosis in sequential frames of a coronary angiogram, allowing it to be scrutinized at high display frame rates. The purpose of this study was to determine whether this technique improves visual detection of low-contrast luminal morphological features. METHODS AND RESULTS: An observer detection study was conducted using computer-simulated arterial segments containing known target features, inserted into clinical digital coronary angiograms. Four observers performed a forced-choice detection of a simulated filling defect in each of 320 angiograms using the conventional and stenosis-stabilized dynamic displays (at 7.5, 15, and 32 frames per second) and a single-frame static display (total of 8960 detections). In a second simulated clinical task, three observers detected a bridging stenotic lumen in 600 angiograms using the two displays (3600 detections). In a third experiment, two angiographers rated the likelihood of intraluminal thrombus in 89 right coronary digital angiograms by consensus reading with both dynamic displays. Detectability of the simulated filling defect was similar for both dynamic display methods at 7.5 frames per second (averaging twice that for static images). As display rate was increased to 32 frames per second, detectability for the conventional display declined, whereas the stabilized display detectability increased for all observers (P < .05). On average, stabilization allowed detection of filling defects equivalent to a 71% increase in feature contrast. Response time for the conventional display averaged 12.9 +/- 4.7 seconds. For the stenosis-stabilized display, response time fell with increased frame rate (P < .05) to 4.9 +/- 1.2 seconds at 32 Hz, similar to the time for static images (4.6 +/- 0.8 seconds). The detectability of the bridging stenotic lumen was increased by 62% with the stabilization compared with conventional dynamic display (P < .00001). Consensus reading of coronary angiograms showed differences between the two dynamic display methods (kappa = 0.11) that may be explained by an improvement in observer uncertainty. A rating of definite for thrombus present or absent was more frequent with the stabilized display (39% versus 15%, P < .0001). CONCLUSIONS: These data suggest that stabilized display of coronary angiograms significantly increases detectability, reduces the time required for detection, and improves observer uncertainty for the presence of small luminal morphological features. The method of angiographic display may thus have an impact on clinical coronary angiographic interpretation. PMID- 8205685 TI - Reduction of radiation exposure while maintaining high-quality fluoroscopic images during interventional cardiology using novel x-ray tube technology with extra beam filtering. AB - BACKGROUND: Radiographic technology plays an integral role in interventional cardiology. The number of interventions continues to increase, and the associated radiation exposure to patients and personnel is of major concern. This study was undertaken to determine whether a newly developed x-ray tube deploying grid switched pulsed fluoroscopy and extra beam filtering can achieve a reduction in radiation exposure while maintaining fluoroscopic images of high quality. METHODS AND RESULTS: Three fluoroscopic techniques were compared: continuous fluoroscopy, pulsed fluoroscopy, and a newly developed high-output pulsed fluoroscopy with extra filtering. To ascertain differences in the quality of images and to determine differences in patient entrance and investigator radiation exposure, the radiated volume curve was measured to determine the required high voltage levels (kVpeak) for different object sizes for each fluoroscopic mode. The fluoroscopic data of 124 patient procedures were combined. The data were analyzed for radiographic projections, image intensifier field size, and x-ray tube kilovoltage levels (kVpeak). On the basis of this analysis, a reference procedure was constructed. The reference procedure was tested on a phantom or dummy patient by all three fluoroscopic modes. The phantom was so designed that the kilovoltage requirements for each projection were comparable to those needed for the average patient. Radiation exposure of the operator and patient was measured during each mode. The patient entrance dose was measured in air, and the operator dose was measured by 18 dosimeters on a dummy operator. Pulsed compared with continuous fluoroscopy could be performed with improved image quality at lower kilovoltages. The patient entrance dose was reduced by 21% and the operator dose by 54%. High output pulsed fluoroscopy with extra beam filtering compared with continuous fluoroscopy improved the image quality, lowered the kilovoltage requirements, and reduced the patient entrance dose by 55% and the operator dose by 69%. CONCLUSIONS: High-output pulsed fluoroscopy with a grid-switched tube and extra filtering improves the image quality and significantly reduces both the operator dose and patient dose. PMID- 8205686 TI - Expression of type 1 plasminogen activator inhibitor in chronic pulmonary thromboemboli. AB - BACKGROUND: Chronic thromboembolic pulmonary hypertension is the result of nonresolving pulmonary emboli that lead to chronic obstruction of the central pulmonary arteries. METHODS AND RESULTS: To determine if the failure to lyse pulmonary thromboemboli is caused by the local expression of the primary inhibitor of tissue-type plasminogen activator (type 1 plasminogen activator inhibitor, PAI-1), levels of PAI-1 antigen and mRNA were analyzed by immunohistochemistry and in situ hybridization in specimens harvested from a series of patients during pulmonary thromboendarterectomies. Red, fibrin-rich thrombi within the thromboendarterectomy specimens were lined with a single layer of endothelial cells exhibiting high levels of PAI-1 antigen. Quantitation of the in situ hybridization signal revealed that a significant increase in PAI-1 mRNA was present in the endothelial cells lining the fresh thrombi in comparison to the signal present in the endothelial cells from noninvolved areas of patients' pulmonary arteries (n = 16, P < .001). In contrast, tissue-type plasminogen activator antigen levels were low in all samples. Yellowish-white thrombi were composed of smooth muscle cells and endothelial cells in numerous vessels that stained prominently for PAI-1 antigen. Both types of cells within the highly organized tissues also exhibited elevated PAI-1 mRNA levels in comparison to patient pulmonary artery specimens that were free of thrombus (n = 16, P < .02). CONCLUSIONS: The prevalence of PAI-1 expression within pulmonary thromboemboli suggests that this inhibitory may play a role in the stabilization of vascular thrombi. PMID- 8205687 TI - Pulmonary hypertension in patients with human immunodeficiency virus infection. Comparison with primary pulmonary hypertension. AB - BACKGROUND: Previously reported cases of patients with pulmonary hypertension (PH) and human immunodeficiency virus (HIV) infection are poorly documented regarding baseline hemodynamics and potential for pulmonary vasodilatation. The purpose of this report was to compare HIV-infected patients who had PH with non HIV-infected patients who had primary pulmonary hypertension (PPH) in terms of (1) clinical characteristics, (2) hemodynamics in baseline conditions and during a short-term vasodilator trial with epoprostenol, and (3) survival. METHODS AND RESULTS: Between April 1987 and August 1992, 20 HIV-infected patients with PH and 93 non-HIV-infected patients with PPH were referred to our department. At the time of referral, baseline right-side heart hemodynamics were obtained in addition to demographic variables and medical history. A short-term vasodilator trial with epoprostenol was performed in 19 of 20 HIV-infected and 86 of 93 non HIV-infected patients. Outcome and survival were analyzed and compared for both groups (22 transplant recipients were excluded from the group of patients with PPH). At the time of diagnosis of PH, HIV-infected patients significantly differed from non-HIV-infected patients in age (32 +/- 5 versus 42 +/- 13 years; P < .05) and degree of disability (New York Heart Association functional class III or IV, 50% versus 75%; P < .01). The proportion of disease states known to be associated with PPH (Raynaud's phenomenon, migraine, collagen disease without overt symptoms and signs, or a positive family history of PPH) was similar in the two groups. HIV-infected patients had a severe but significantly lower level of PH than patients with PPH. The percentage of responders to epoprostenol and the level achieved in pulmonary vasodilatation were similar in the two groups. PH was the cause of death in 8 of the 10 HIV-infected patients who died within 1 year after the diagnosis of PH. Overall survival was poor and not significantly different between the two groups. Pathological findings in lung tissue obtained from 3 HIV-infected patients were close to those seen in most of the lung specimens available from 27 patients with PPH and resembled plexogenic pulmonary arteriopathy. CONCLUSIONS: These results support the view that HIV infection may now be regarded as another common disease state that can be associated with PPH development. The lower initial severity in HIV-infected patients may be due to the close medical attention usually devoted to such patients, who may account for an earlier diagnosis. However, the overall survival rate of HIV-infected patients with PH appeared to be as poor as in non-HIV-infected patients with PPH. PMID- 8205688 TI - Adenosine deaminase and carcinoembryonic antigen in pericardial effusion diagnosis, especially in suspected tuberculous pericarditis. AB - BACKGROUND: Adenosine deaminase (ADA) and carcinoembryonic antigen (CEA) have been measured in pleural fluid to help distinguish malignant from benign effusions, especially in tuberculous pleurisy. We investigated ADA and CEA levels in patients with moderate to large pericardial effusions of different etiologies. METHODS AND RESULTS: We performed diagnostic and therapeutic pericardiostomy with drainage and biopsy. We measured ADA and CEA levels in the pericardial fluid in 26 patients with moderate to large pericardial effusion and 19 control patients. Patients were included in a prospective protocol from August 1991 to August 1993. Patients were grouped as follows: group 1, 9 patients with tuberculous pericarditis (TP) confirmed by bacteriologic culture or histology of pericardial biopsy; group 2, 5 patients with clinically strongly suspected TP; group 3, 12 patients with malignancy (8) and acute pericarditis (4); group 4, 19 control patients without pericardial disease. We treated patients with TP with isoniazid, rifampin, and either streptomycin or ethambutol for 12 months and pyrazinamide for 2 months. We observed for symptoms and signs of recurrent pericarditis or constrictive pericarditis on follow-up. In group 1 the ADA activity was significantly higher (101 +/- 14 U/L) than that in group 3 (22 +/- 5 U/L) or that in group 4 (17 +/- 2 U/L) (P < .05). There was no significant difference between ADA activity in group 1 (101 +/- 14 U/L) and that in group 2 (100 +/- 26 U/L). With a cutoff value for ADA activity of 40 U/L, sensitivity was 93% and specificity 97% in the diagnosis of TP. In benign diseases, the CEA level was significantly lower (1.0 +/- 0.3 ng/mL) than that in malignant diseases (135.1 +/ 79.7 ng/mL) (P < .05). With a cutoff value for CEA level of 5 ng/mL, sensitivity was 75% and specificity 100% in the diagnosis of malignant pericarditis. Follow up study (mean, 12.9, 19.8, and 11.8 months in groups 1, 2, and 3, respectively, showed no symptoms or signs of constrictive pericarditis, except for 1 patient. CONCLUSIONS: Pericardial fluid ADA and CEA are useful for the differential diagnosis of pericardial effusion of various causes. They also have great value in early diagnosis of TP, particularly when the results of other clinical and laboratory tests are negative. PMID- 8205689 TI - Reduced calcium currents in subendocardial Purkinje myocytes that survive in the 24- and 48-hour infarcted heart. AB - BACKGROUND: The abnormal transmembrane action potentials of subendocardial Purkinje fibers that survive 24 to 48 hours after coronary artery occlusion can be a source of the multiform ventricular tachycardias that occur during this time. A change in the density or function of either or both the T-type and L-type cardiac Ca2+ channels may contribute to the altered electrical activity of these Purkinje myocytes. METHODS AND RESULTS: The purpose of this study was to determine the function of the T- and L-type Ca2+ currents (iCat and iCaL, respectively) in Purkinje myocytes dispersed from the subendocardium of the left ventricle 24 and 48 hours after coronary artery occlusion (IZPC24 and IZPC48, respectively). To do this we compared whole-cell Ca2+ currents from Purkinje myocytes enzymatically dispersed from free-running fiber bundles (SPCs), from the subendocardium of the noninfarcted canine heart (NZPCs), and from IZPC24 and IZPC48. ICaL and iCat were recorded with Cs(+)- and EGTA-rich pipettes and in Na(+)-K(+)-free external solutions to eliminate overlapping currents. ICaL density was significantly reduced in IZPC48 compared with NZPC or IZPC24. This was not accompanied by a shift in the current-voltage relation or by a change in the time course of decay of iCaL. Replacement of Ca2+ with equimolar Ba2+ increased iCaL density in all cell types, but peak iBaL of IZPC48 remained reduced compared with control iBaL values. T-type Ca2+ currents were recorded in all SPCs and NZPCs. In IZPC24 and IZPC48 there was a reduction in peak iCat amplitudes and densities. This was not accompanied by a shift in the current voltage relation or by a change in the time course of decay of peak iCat. However, there was a hyperpolarizing shift in the steady-state availability relations in both IZPC24 and IZPC48. In addition, the maximally available iCat in IZPC24 was not different from control, whereas it was significantly reduced in IZPC48. CONCLUSIONS: The L-type ICa density in subendocardial Purkinje myocytes that survive in the infarcted heart is significantly decreased by 48 hours after the time of coronary artery occlusion. The peak T-type ICa density is decreased in subendocardial Purkinje myocytes that survive in the infarcted heart at 24 hours, but further reduction occurs in these myocytes by 48 hours. This loss in Ca2+ channel function could contribute to the abnormal transmembrane potentials of these myocytes surviving in the infarcted heart. PMID- 8205690 TI - Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the beta 1-adrenoceptor with positive chronotropic effect. AB - BACKGROUND: Autoantibodies against the beta 1-adrenoceptor have been detected in the sera of patients with idiopathic dilated cardiomyopathy (DCM). The mechanisms by which these autoantibodies can alter normal receptor function are investigated, and the results are interpreted in the light of the beneficial effects of beta 1-blockade in some of these patients. METHODS AND RESULTS: Autoantibodies against the beta 1-adrenoceptor, affinity purified from sera of patients with idiopathic DCM, were analyzed in a functional test system of spontaneously beating neonatal rat heart myocytes. Antibodies from rabbits immunized with peptides derived from the amino acid sequence of this receptor were also analyzed. Autoantibodies, against the second extracellular loop increased the beating frequency of isolated myocytes in a concentration-dependent manner, to approximately 80% of maximal isoproterenol stimulation. Rabbit anti peptide antibodies against the second extracellular loop increased the beating frequency correspondingly. Autoantibodies and rabbit anti-peptide antibodies against the second extracellular loop were able to immunoprecipitate the unliganded receptor but not the antagonist-occupied receptor. In contrast, rabbit antibodies against the extracellular N-terminal sequence 34-57 of the beta 1 adrenoceptor were able to immunoprecipitate both the unliganded and the antagonist-occupied receptor although with no effect on the beating frequency of myocytes. The positive chronotropic effect of the antibodies was completely neutralized both by the addition of increasing concentrations of the beta 1 selective antagonist bisoprolol and by preincubation with the peptide corresponding to the second extracellular loop. The antibody-induced increase in beating frequency remained unchanged for more than 6 hours. This should be compared with the isoproterenol-stimulated beating frequency, which undergoes desensitization within 60 minutes. Addition of isoproterenol to autoantibody stimulated myocytes resulted in only a small increase in beating frequency and did not cause desensitization. Antibodies had only a marginal effect on cyclic AMP production of stimulated cardiomyocytes compared with the 10-fold increase obtained after stimulation with isoproterenol. CONCLUSIONS: The second extracellular loop of the beta 1-adrenoceptor is a specific target for antibodies with stimulatory activity detected in patients with idiopathic DCM. The antibodies have a positive chronotropic effect on isolated rat heart myocytes. Autoantibody stimulation does not cause the normal agonist-induced desensitization phenomena of the effector system. These findings could contribute to our understanding of the pathophysiological mechanisms of the autoantibodies and of the beneficial effect of beta 1-blocking agents in the treatment of patients with idiopathic DCM. PMID- 8205691 TI - In vivo blockade of tumor necrosis factor-alpha in cholesterol-fed rabbits after cardiac transplant inhibits acute coronary artery neointimal formation. AB - BACKGROUND: We previously identified in piglet cardiac allografts an immunoinflammatory response in coronary arteries in which increased fibronectin regulated by interleukin-1 beta was associated with early evidence of intimal thickening. In the present study, we used rabbits to assess whether acute neointimal formation after cardiac transplantation was reduced by blockade of tumor necrosis factor (TNF)-alpha, which modulates interleukin-1 beta, or by cyclosporine A. METHODS AND RESULTS: Sixteen rabbits underwent heterotopic cardiac transplantation and were given saline, TNF-soluble receptor (sr), or cyclosporine A. In host hearts from saline- or TNFsr-treated groups, few coronary arteries (approximately 13% to 16%) had intimal thickening, whereas values were higher in the cyclosporine A-treated group (approximately 30%). In donor hearts from the saline-treated group, however, approximately 68% of vessels had intimal thickening versus approximately 32% in TNFsr- and approximately 30% in cyclosporine A-treated groups (P < .01 for both). Severity of intimal thickening assessed quantitatively as percent vessel area was approximately 38% in the saline-treated group but reduced in TNFsr- and cyclosporine A-treated groups to approximately 22% and 18%, respectively (P < .01 for each). Immunohistochemistry revealed increased staining for major histocompatibility complex II, T cells, interleukin-1 beta, TNF-alpha, and fibronectin in donor coronary arteries from saline-treated animals when compared with TNFsr- and cyclosporine A-treated animals. Grade 3 myocardial rejection was observed in both saline- and TNFsr treated groups, but only grade 1 was apparent in the cyclosporine A-treated group. CONCLUSIONS: In vivo blockade of TNF-alpha suppresses the acute development of neointimal formation by selectively reducing the vascular immunoinflammatory reaction and accumulation of fibronectin, whereas cyclosporine A suppresses both the myocardial and the vascular immune reaction. PMID- 8205692 TI - Alterations in coronary artery vascular reactivity of hypertensive Ren-2 transgenic rats. AB - BACKGROUND: The renin-angiotensin system and endothelium-derived nitric oxide (EDNO) are important regulators of vascular tone. This study was designed to investigate endothelial and vascular smooth muscle function in coronary arteries of Ren-2 transgenic rats. METHODS AND RESULTS: Left anterior descending coronary arteries and aortas were isolated from transgenic rats and Sprague-Dawley control rats at 6 (young) and 12 (adult) weeks of age and examined in myographs or organ chambers for isometric tension recording. Systolic blood pressure was significantly higher in transgenic rats (young, 229 +/- 6 mm Hg; adult, 239 +/- 8 mm Hg) than in control rats (young, 126 +/- 2 mm Hg; adult, 118 +/- 3 mm Hg; P < .005). N omega-Nitro-L-arginine methyl ester (L-NAME, 10(-7) to 10(-4) mol/L) evoked marked endothelium-dependent contractions in coronary arteries (young, 52 +/- 8% of the contraction to 100 mmol/L KCl; adult, 40 +/- 8%) but not aortas (young, 3 +/- 1%; adult, 2 +/- 1%). In coronary arteries, this response was significantly smaller in adult (n = 9) than in young (n = 8, P < .05) control rats. Young transgenic rats (56 +/- 9%, n = 8) showed slightly stronger contractions in response to L-NAME than young control rats (NS), which almost totally disappeared in adult transgenic rats (6 +/- 3%, n = 7; P < .05 versus adult control rats; P < .01 versus young transgenic rats). Endothelium-dependent relaxations in response to acetylcholine (10(-9) to 10(-4) mol/L) were totally blocked by L-NAME (10(-4) mol/L) but were unaffected by the thromboxane receptor antagonist SQ30741 (10(-7) mol/L). This stimulated release of EDNO, endothelium independent relaxations in response to the nitrovasodilator linsidomine (10(-9) to 10(-5) mol/L), and contractions in response to KCl (100 mmol/L) were comparable in all groups of rats. CONCLUSIONS: Ren-2 transgenic rats develop fulminant hypertension that is associated with a selective decrease in endothelium-dependent contractions in response to L-NAME, whereas endothelium dependent relaxations in response to acetylcholine as well as smooth muscle function remain unaffected. PMID- 8205693 TI - New Na(+)-H+ exchange inhibitor HOE 694 improves postischemic function and high energy phosphate resynthesis and reduces Ca2+ overload in isolated perfused rabbit heart. AB - BACKGROUND: Experiments were carried out using the new Na(+)-H+ exchange inhibitor (3-methylsulfonyl-4-piperidinobenzoyl)guanidine methanesulfonate (HOE 694) to assess the role of Na(+)-H+ exchange in myocardial ischemic and reperfusion injury. METHODS AND RESULTS: Three groups of rabbit hearts (n = 5 in each) were perfused with blood and were subjected to 45 minutes of global normothermic (37 degrees C) ischemia, followed by 1 hour of reperfusion. Group 1 was the control group (vehicle only); in group 2, HOE 694 (1 mumol/L) was administered before ischemia (pretreatment group); and in group 3, HOE 694 was given only during reperfusion to separate actions exerted during ischemia from those specifically obtained during reperfusion. End-diastolic pressure rise at 1 hour of reperfusion was reduced by administration of HOE 694 starting before ischemia (from 52.2 +/- 8.5 mm Hg in group 1 to 17.6 +/- 4.5 mm Hg in group 2, P < .01) or starting on reperfusion (28.8 +/- 5.4 mm Hg in group 3, P < .05 versus group 1). Left ventricular developed pressure (LVDP) and its derivative (dP/dt) recovered better in HOE 694-pretreated hearts (LVDP, 79 +/- 9.9 mm Hg in group 2 versus 24.8 +/- 10 mm Hg in group 1; dP/dt, 1580 +/- 198 mm Hg/s versus 340 +/- 221 mm Hg/s, P < .01). In hearts treated only on reperfusion, some improvement was observed, which, however, did not reach statistical significance. Coronary flow on reperfusion was higher in groups 2 and 3 compared with controls, and no "no-reflow" was observed. Two additional groups of hearts were perfused with phosphate-free Krebs-Henseleit solution to enable studies with 31P nuclear magnetic resonance (NMR). ATP was better preserved in HOE 694-pretreated (62 +/- 4.9% of preischemic value) than in control hearts (44 +/- 3.3%) at the end of 30 minutes of reperfusion, and phosphocreatine resynthesis was higher (109 +/- 3.7% versus 86 +/- 5.4%). HOE 694 did not affect the time course of intracellular acidosis during ischemia but suppressed a small alkaline overshoot occurring early in reperfusion (pH 6.96 +/- 0.02 in HOE 694-pretreated hearts versus 7.14 +/- 0.05 in control hearts). Electron microscopy with Ca2+ staining of the blood perfused hearts showed that clumping of Ca2+ aggregates in mitochondria was prevented by HOE 694. CONCLUSIONS: Postischemic dysfunction was associated with a rise in end-diastolic pressure. This rise was effectively blocked by HOE 694. The drug was most effective when hearts were treated before ischemia, although partial protection was observed when administration was started on reperfusion. The action of HOE 694 strengthens the idea that Na(+)-H+ exchange during both ischemia and reperfusion contributes to contractile dysfunction. PMID- 8205694 TI - Role of vascular endothelium in exercise-induced dilation of large epicardial coronary arteries in conscious dogs. AB - BACKGROUND: The role of vascular endothelium in the control of epicardial coronary artery vasomotion during treadmill exercise remains unclear. Therefore, we examined the consequences of in vivo balloon endothelial denudation on external coronary diameter of the left circumflex artery during exercise in conscious dogs. METHODS AND RESULTS: Seven dogs instrumented for the measurement of arterial blood pressure, external coronary artery diameter, and coronary blood flow were studied during exercise before and up to 21 days after balloon endothelial denudation of the proximal left circumflex artery. Endothelial denudation was confirmed by abolition of the epicardial coronary artery dilation induced by acetylcholine (0.3 microgram/kg IV) and reactive hyperemia. Epicardial coronary vasodilation was observed in the control state during treadmill exercise (+5.2 +/- 1.0%). In contrast, a marked vasoconstriction was observed 3 (-4.6 +/- 0.6%) and up to 6 days after endothelial denudation. Complete epicardial coronary artery dilation in response to acetylcholine and exercise was restored 9 days after endothelial denudation. In addition, epicardial coronary artery vasomotor responses to acetylcholine and treadmill exercise were closely correlated (r = .82, P < .001). Reactive dilation was not completely restored 21 days after endothelial denudation, but reactive hyperemia and exercise vasomotor responses during the 21 days follow-up were correlated (r = .70, P < .001). Vasodilation induced by nitroglycerin (1 microgram/kg IV) was reduced by 25% (P < .01) 3 days after endothelial denudation and returned to its corresponding control level 3 days later. Prazosin (50 micrograms/kg IV) significantly attenuated the exercise induced coronary artery constriction after endothelial denudation (+1.5 +/- 1.4% versus -4.6 +/- 1.0%). CONCLUSIONS: These data demonstrate that endothelium is essential for the mediation of epicardial coronary dilation during exercise and may protect these vessels against the vasoconstrictor effect of endogenous catecholamines. PMID- 8205695 TI - Differences in compensatory vessel enlargement, not intimal formation, account for restenosis after angioplasty in the hypercholesterolemic rabbit model. AB - BACKGROUND: In de novo human atherosclerosis, compensatory vessel enlargement limits the effect of intimal plaque formation on lumen narrowing. We hypothesized that arterial remodeling may also play an important role in determining the chronic lumen size after angioplasty and tested this hypothesis using the hypercholesterolemic rabbit iliac artery angioplasty model. METHODS AND RESULTS: Morphometric analysis of histological cross-sectional areas of vessels from animals killed immediately after angioplasty (acute group, n = 11) were compared with the same areas from animals killed 4 weeks after the procedure (chronic group, n = 37), when restenosis occurs in this model. The area circumscribed by the internal elastic lamina (IEL) increased by 20% from acute to 4 week follow-up after angioplasty (acute group, 2.36 +/- 0.45 mm2, chronic group, 2.84 +/- 0.89 mm2). Over the same time period, intimal area increased by 0.82 mm2. Despite this increase in intimal area, lumen area decreased by only 0.34 mm2 because of the compensatory enlargement of the IEL area. In the chronic group, polynomial regression analysis revealed a quadratic relation between intimal area and lumen area (R2 = .35, P < .001). A lumen area of 0.45 mm2 (the nadir of the quadratic relation) was used to divide the chronic group into two subgroups: restenotic (n = 21; lumen area, < 0.45 mm2) and nonrestenotic (n = 16; lumen area, > 0.45 mm2). By definition, there was a significant difference in lumen area between the two subgroups (0.15 +/- 0.15 mm2 for restenotic; 0.73 +/- 0.18 mm2 for nonrestenotic). Surprisingly, the intimal areas in the two subgroups were virtually identical (2.41 +/- 0.92 mm2 for restenotic, 2.49 +/- 0.69 mm2 for nonrestenotic, P = NS). The difference in the lumen area between restenotic and nonrestenotic vessels was a result of the significantly greater IEL area in the nonrestenotic subgroup (3.22 +/- 0.83 mm2 for nonrestenotic, 2.56 +/- 0.84 mm2 for restenotic, P < .05). In both restenotic and nonrestenotic vessels, the IEL area increased with increases in intimal area. In the restenotic arteries, the slope of this correlation was < 1, showing inadequate compensatory enlargement for the intimal plaque. In the nonrestenotic vessels, the slope was > 1, limiting the effect of intimal plaque on luminal narrowing. CONCLUSIONS: These data indicate that the iliac artery in an atherosclerotic rabbit model compensates for intimal formation after angioplasty by vessel enlargement. Furthermore, the degree of vessel enlargement is more important than intimal area in determining the chronic lumen size. PMID- 8205696 TI - The relative importance of arterial remodeling compared with intimal hyperplasia in lumen renarrowing after balloon angioplasty. A study in the normal rabbit and the hypercholesterolemic Yucatan micropig. AB - BACKGROUND: Although arterial renarrowing after angioplasty has been attributed largely to intimal hyperplasia, there has been no systematic effort to correlate the actual hyperplastic tissue mass with angiographic lumen reduction. Using balloon angioplasty in various animal restenosis models, we quantitatively assessed the separate contributions of intimal hyperplasia and arterial remodeling to angiographic late lumen loss. METHODS AND RESULTS: Data used for this study were obtained from experiments of conventional and thermal (37 degrees C or 55 degrees to 90 degrees C) balloon angioplasty-treated femoral and iliac arteries in normal rabbits and conventional balloon angioplasty-treated iliac arteries in Yucatan micropigs fed either a normal or an atherogenic diet. Quantitative angiography was performed immediately before and after intervention and at 3 or 8 weeks thereafter, and late loss in lumen diameter was taken as the difference between arterial diameter immediately after treatment and at 3 or 8 weeks of follow-up. Intimal hyperplasia was quantified histologically as the area of tissue mass within the internal elastic lamina. We observed a consistent discrepancy between the actual late loss seen with angiography and the diameter reduction that could be explained by histological intimal thickness alone in both animal models. This discrepancy ranged from 86 +/- 3% of the late loss in the 8 weeks/37 degrees C group to 77 +/- 22% in the conventional group for rabbits and 52 +/- 23% in an atherogenic diet group (n = 10) to 89 +/- 11% in a normal diet group (n = 6) for pigs. This discrepancy appeared to be due predominantly to reduction of the area circumscribed by the internal elastic membrane, a process that is tentatively designated as arterial remodeling. In both the rabbit femoral artery and in the Yucatan iliac artery, remodeling, not intimal hyperplasia, correlated with angiographic late loss. CONCLUSIONS: In both the normal rabbit and the normal and atherosclerotic pig, restenosis after angioplasty results from both intimal hyperplasia and arterial remodeling. The exact etiology of arterial renarrowing after angioplasty has important implications on the design of antirestenosis drugs and new coronary devices. PMID- 8205697 TI - Blockade of platelet membrane glycoprotein Ib receptors delays intracoronary thrombogenesis, enhances thrombolysis, and delays coronary artery reocclusion in dogs. AB - Von Willebrand factor and platelet membrane glycoprotein Ib receptors interact to mediate platelet adhesion and thrombogenesis in stenosed and endothelium-injured arteries. We wished to determine whether blocking glycoprotein Ib receptors with a recombinant von Willibrand factor binding domain (VCL) increases the time required for thrombus formation after injury to the coronary arteries. We also wished to determine whether, after thrombolysis with tissue plasminogen activator (TPA), VCL delays or protects against coronary artery reocclusion. Twenty-seven dogs were treated with either saline, VCL, or aspirin before thrombosis was induced in their coronary arteries by electrical injury. The time from injury to the formation of occlusive thrombi was significantly greater with VCL (70 +/- 10 minutes) and aspirin (69 +/- 20 minutes) than with saline (18 +/- 3 minutes, P < .001 and P < .05). Thrombosis was induced in 30 other dogs that then received thrombolytic treatment in four groups. Our major finding was that coronary artery reocclusion occurred in 72 +/- 11 minutes after treatment with TPA (80 micrograms/kg + 8 micrograms.kg-1.min-1) and heparin (200 U/kg) (n = 7); in 142 +/- 24 minutes after TPA, heparin, and VCL (4 mg/kg + 2 mg.kg-1.h-1) (n = 7) (compared with TPA and heparin, P < .05); in 74 +/- 13 minutes after TPA, heparin, and aspirin (5 mg/kg) (n = 8); and in 173 +/- 8 minutes after TPA, heparin, VCL, and aspirin (n = 8) (compared with TPA and heparin, P < .001). Thus, VCL increases the length of time required for thrombus formation in coronary arteries, and, when given with TPA and heparin, delays coronary artery reocclusion more effectively than aspirin. PMID- 8205698 TI - Probucol promotes endogenous antioxidants and provides protection against adriamycin-induced cardiomyopathy in rats. AB - BACKGROUND: The potential usefulness of adriamycin (ADR) is restricted because of its cardiotoxic side effects. Since free radicals and lipid peroxidation are suggested to be involved in ADR cardiomyopathy, we examined the beneficial effects of probucol, a lipid-lowering drug with strong antioxidant properties. METHODS AND RESULTS: ADR was administered to rats in six equal intraperitoneal injections over a period of 2 weeks (cumulative dose of 15 mg/kg). After a 3-week posttreatment period, cardiomyopathy and congestive heart failure were characterized by ascites, congested liver, depressed cardiac function, elevated left ventricular end-diastolic pressure, and myocardial cell damage. Myocardial glutathione peroxidase (GSHPx) activity was decreased, and lipid peroxidation was increased. Probucol (cumulative dose, 60 mg/kg IP) was administered in six equal injections over a 2-week period on days alternating with ADR treatment. Probucol significantly attenuated the myocardial effects of ADR, improved left ventricular function, and lowered mortality as well as the amount of ascites. Treatment with probucol was also accompanied by an increase in myocardial GSHPx and superoxide dismutase activities, with a concomitant decrease in lipid peroxidation. CONCLUSIONS: These data provide evidence that ADR cardiomyopathy is associated with an antioxidant deficit. Improved cardiac function resulting from treatment with probucol may be related to the maintenance of the antioxidant status of the heart. The study suggests potential usefulness of antioxidant (probucol) therapy in ADR cardiomyopathy. PMID- 8205699 TI - Cytokine and murine coxsackievirus B3 myocarditis. Interleukin-2 suppressed myocarditis in the acute stage but enhanced the condition in the subsequent stage. AB - BACKGROUND: It has been shown that the development of coxsackievirus B3 (CB3) myocarditis is regulated by T cells and not by B cells. Interleukin-2 (IL-2) is a T-cell-derived cytokine that stimulates the growth of T cells. This study was carried out to determine the effects of IL-2 on CB3-infected BALB/c mice. METHODS AND RESULTS: In two separate experiments, recombinant human IL-2 (5 x 10(4) U) was administered subcutaneously to 30 mice early (days 0 to 7) and 30 mice late (days 7 to 14) after infection with CB3. Each experiment had a control group of infected animals that did not receive IL-2. On days 7 and 10, splenic natural killer (NK) cell activity determined by 51Cr release assay and the distribution of myocardial lymphocyte subsets were compared in the treated and untreated groups. In the early treatment experiment, survival at 7 days was higher in treated compared with control animals, myocardial virus titers were lower, inflammatory cell infiltration was less (as was the severity of necrosis at the time the mice were killed), and NK cell activity was higher. However, in the late treatment experiment, survival at 14 days was lower in treated compared with control animals, and there was more infiltration, more severe necrosis, and more T-cell infiltration, but the NK cell activity did not differ significantly. In a third experiment similar to the late experiment described above but involving infected athymic nude mice, we confirmed the lack of effect of late in vivo administration of IL-2 on outcome. CONCLUSIONS: IL-2 has the capacity to limit CB3 myocarditis by enhancing NK cell activity in the acute viremic stage, resulting in a reduction of cardiac pathology. However, in the subacute aviremic stage, in contrast, IL-2 exacerbates the course and severity of the disease by increasing the number of T cells infiltrating the myocardium. That is, IL-2 has differential effects on acute CB3 myocarditis. IL-2 is beneficial if treatment is given early but later in murine CB3 myocarditis. PMID- 8205700 TI - Abnormalities of cardiac sympathetic function in pacing-induced heart failure as assessed by [123I]metaiodobenzylguanidine scintigraphy. AB - BACKGROUND: Increased activity of the sympathetic nervous system contributes significantly to the pathophysiology of heart failure. However, cardiac efferent sympathetic function has not been well characterized in this disorder. In this study, we evaluated cardiac sympathetic innervation using [123I]metaiodobenzylguanidine (MIBG) and compared this with left ventricular (LV) tissue norepinephrine concentration and myocardial perfusion, assessed by 201Tl, in a canine model of heart failure. METHODS AND RESULTS: Planar and tomographic cardiac imaging was performed for MIBG and 201Tl in 23 dogs: 8 normal dogs (group 1) and 15 dogs with heart failure induced by right ventricular pacing at 250 beats per minute either continuously for 3 weeks (group 2) or intermittently for 7 weeks (group 3). Plasma and LV tissue norepinephrine concentrations were also measured. Scintigraphic studies in group 2 demonstrated reduced cardiac MIBG activity at heart failure (0.17 +/- 0.04 versus 0.29 +/- 0.05 counts per megabecquerel per pixel at baseline, mean +/- SD; P = .0001), whereas thallium activity was unchanged from baseline. This reduction in cardiac MIBG activity with heart failure was associated with increased intraimage variability in the distribution of MIBG activity (21 +/- 8% versus 13 +/- 7% at baseline, mean +/- SD; P = .0001). The MIBG heart-to-lung ratio was calculated for all groups to control for the inhibitory effect that plasma norepinephrine has on the neuronal uptake of MIBG. There was a positive correlation between LV tissue norepinephrine and the MIBG heart-to-lung ratio (r = .67; P < .001; n = 22), for which the group 2 heart failure animals had the lowest values. No relation existed between plasma norepinephrine concentration and the MIBG heart-to-lung ratio. In addition, regional LV tissue norepinephrine concentration and MIBG activity were both lowest at the apex in normal (group 1) and heart failure (group 2) dogs. The MIBG heart-to-lung ratio also correlated inversely with cardiac filling pressure (r = .59; P < .05) and heart rate (r = -.65; P < .01) and positively with cardiac output (r = .53; P < .05). CONCLUSIONS: Heart failure is associated with severe cardiac adrenergic dysfunction manifested by reduced MIBG activity and increased heterogeneity in the LV distribution of MIBG. Furthermore, MIBG scintigraphy is a simple noninvasive method for assessing global and regional LV tissue norepinephrine levels. PMID- 8205701 TI - Effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction. AB - BACKGROUND: Recent clinical trials have suggested that therapy with angiotensin converting enzyme inhibitors in asymptomatic patients with reduced left ventricular (LV) function can significantly reduce the incidence of congestive heart failure compared with patients receiving placebo. In the present study, we examined the effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of LV systolic dysfunction and LV chamber enlargement in dogs with reduced LV ejection fraction (EF). METHODS AND RESULTS: LV dysfunction was produced in 28 dogs by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LVEF was 30% to 40%. Three weeks after the last embolization, dogs were randomized to 3 months of oral therapy with enalapril (10 mg twice daily, n = 7), metoprolol (25 mg twice daily, n = 7), digoxin (0.25 mg once daily, n = 7), or no treatment (control, n = 7). As expected, in untreated dogs, LVEF decreased (36 +/- 1% versus 26 +/- 1%, P < .001) and LV end-systolic volume (ESV) and end-diastolic volume (EDV) increased during the 3-month follow-up period (39 +/- 4 versus 57 +/- 6 mL, P < .001, and 61 +/- 6 versus 78 +/- 8 mL, P < .002, respectively). In dogs treated with enalapril or metoprolol, LVEF remained unchanged or increased after therapy compared with before therapy (35 +/- 1% versus 38 +/- 3% and 35 +/- 1% versus 40 +/- 3%, respectively, P < .05), whereas ESV and EDV remained essentially unchanged. In dogs treated with digoxin, EF remained unchanged but ESV and EDV increased significantly. CONCLUSIONS: In dogs with reduced LVEF, long-term therapy with enalapril or metoprolol prevents the progression of LV systolic dysfunction and LV chamber dilation. Therapy with digoxin maintains LV systolic function but does not prevent progressive LV enlargement. PMID- 8205702 TI - Mechanism of interruption of atrial flutter by moricizine. Electrophysiological and multiplexing studies in the canine sterile pericarditis model of atrial flutter. AB - BACKGROUND: Moricizine is said to have potent effects on cardiac conduction but little or no effect on cardiac refractoriness. METHODS AND RESULTS: The effects of moricizine (2 mg/kg IV) on induced atrial flutter were studied 2 to 4 days after the creation of sterile pericarditis in 11 dogs. Ten episodes of stable atrial flutter before and after the administration of moricizine were studied in 9 dogs in the conscious, nonsedated state, and 7 episodes were studied in 6 dogs in the anesthetized, open chest state. In the conscious state, the effects of moricizine on atrial excitability, atrial effective refractory period, and intra atrial conduction times were studied by recording during overdrive pacing of sinus rhythm from epicardial electrodes placed at selected atrial sites. Moricizine prolonged the atrial flutter cycle length in all the episodes, from a mean of 133 +/- 9 to 172 +/- 27 milliseconds (P < .001), and then terminated 7 of the 10 episodes. Moricizine increased the atrial threshold of excitability from a mean of 2.3 +/- 1.4 to 3.3 +/- 2.2 mA (P < .01) and prolonged intra-atrial conduction times (measured from the sulcus terminalis to the posteroinferior left atrium) from a mean of 58 +/- 6 to 64 +/- 5 milliseconds (P < .005). Prolongation of the atrial effective refractory period from 166 +/- 20 to 174 +/- 24 milliseconds (P < .05) was observed only at the sulcus terminalis site. In the open chest studies, administration of moricizine prolonged the atrial flutter cycle length from a mean of 150 +/- 15 to 216 +/- 30 milliseconds (P < .001) and then terminated the atrial flutter in all 7 episodes. As demonstrated by simultaneous multisite mapping from 95 bipolar sites on the right atrial free wall, the atrial flutter cycle length prolongation was either due to further slowing of conduction in an area of slow conduction in the reentrant circuit of the atrial flutter (5 episodes) or further slowing of conduction in an area of slow conduction plus the development of a second area of slow conduction (2 episodes). The change in conduction times in the rest of the reentrant circuit was negligible (10.9 +/- 8.7% of the total change). In all 7 episodes, the last circulating reentrant wave front blocked in an area of slow conduction. CONCLUSIONS: Moricizine (1) prolongs the atrial flutter cycle length, primarily by slowing conduction in an area of slow conduction in the reentrant circuit, (2) terminates atrial flutter by causing block of the circulating reentrant wave front in an area of slow conduction of the reentrant circuit, and (3) effectively interrupts otherwise stable atrial flutter in this canine model. The reason for these effects of moricizine are not readily explained by its effects on global atrial conduction times and refractoriness studied during sinus rhythm. Local changes in conduction in an area(s) of slow conduction are responsible for both cycle length prolongation and atrial flutter termination rather than the traditional wavelength concept of head-tail interaction. PMID- 8205703 TI - Modulation of procainamide's effect on cardiac conduction in dogs by extracellular potassium concentration. A quantitative analysis. AB - BACKGROUND: Antiarrhythmic drugs are known to have state-dependent interactions with cardiac sodium channels, and these have potentially important implications for drug effects on cardiac conduction, particularly in situations of changed resting potential and heart rate. Recent advances in theoretical approaches permit beat-to-beat changes in sodium channel block to be inferred from conduction changes in vivo and allow for an analysis of state-dependent drug action from conduction changes occurring on the onset of pacing at different rates. The purpose of the present study was to use this method to analyze the interaction between hyperkalemia and procainamide's sodium channel-blocking action in terms of resulting changes in left ventricular conduction. METHODS AND RESULTS: Epicardial mapping with a 56-electrode array was used to assess ventricular conduction in open chest, anesthetized mongrel dogs with Formalin induced atrioventricular block. Procainamide was infused as a series of loading and maintenance infusions until at least 20% conduction slowing was obtained at the shortest basic cycle length (300 milliseconds). Results in a control set of normokalemic dogs were compared with results in dogs with moderate hyperkalemia produced by a loading and maintenance infusion of potassium chloride. Plasma procainamide concentration was measured by high-performance liquid chromatography, and the constancy of serum potassium concentration was verified with ion-sensitive electrode measurement. Although hyperkalemia itself (mean +/- SEM potassium concentration, 6.64 +/- 0.66 mmol/L) did not alter conduction, it resulted in substantially increased conduction slowing by procainamide despite substantially lower plasma drug concentrations (102 +/- 10 mumol/L) compared with normokalemic dogs (potassium concentration, 3.87 +/- 0.24 mmol/L; procainamide concentration, 277 +/- 16 mumol/L). The onset of conduction slowing and block followed basic molecular theory, with an exponential time constant that was faster at longer cycle lengths and total block that increased as cycle length decreased. Piecewise exponential analysis of block during the rested and depolarized phases of the action potential showed that the enhancement of procainamide's action by hyperkalemia was due almost exclusively to increased rested-phase block. Hyperkalemia produced a bradycardia-dependent and slight reduction in action potential duration and antagonized the action potential prolonging effect of procainamide, particularly at shorter cycle lengths. CONCLUSIONS: Hyperkalemia strongly enhances procainamide-induced conduction slowing by increasing the interaction between the drug and sodium channels during the rested phase of the cardiac cycle. These results indicate the applicability of basic molecular theories of antiarrhythmic drug action to understanding drug induced changes in conduction velocity in vivo and highlight the potential importance of heterogeneous magnification of sodium channel-blocking drug action by the spatially variable hyperkalemia that occurs with acute myocardial ischemia. The latter could play an important role in the known proarrhythmic potential of sodium channel-blocking drugs in patients with coronary artery disease. PMID- 8205704 TI - Evaluation of mitral regurgitation using a digitally determined color Doppler flow convergence 'centerline' acceleration method. Studies in an animal model with quantified mitral regurgitation. AB - BACKGROUND: The imaging and measurement of the proximal flow convergence region in the left ventricle have been reported to be useful for identifying the site of mitral regurgitation (MR) and for evaluating its severity. However, the application of this method has not gained general acceptance. There have been few in vivo studies with quantified reference standards for determining regurgitant volume, and those that have been reported used spectral Doppler standards and/or nonsimultaneously performed contrast ventriculography. The purpose of the present study was to evaluate the proximal flow convergence centerline velocity-distance profile method applied to chronic MR resulting from flail mitral leaflets in an animal model in which regurgitant flow rates and regurgitant volumes were determined simultaneously with electromagnetic flow probes and flowmeters. METHODS AND RESULTS: In six sheep, a total of 18 hemodynamically different states were obtained when the animals were restudied 6 months after surgical induction of MR produced by severing chordae tendineae to the anterior (three sheep) or posterior (three sheep) mitral leaflet. Echocardiographic studies with a Vingmed 750 were performed to obtain complete proximal axial flow acceleration velocity distance profiles for each hemodynamic state. The color Doppler velocity data were directly transferred in digital format from the ultrasound instrumentation to a microcomputer. The severity of MR was assessed by the magnitude of the mitral regurgitant fraction determined using both mitral and aortic electromagnetic flow probes balanced against each other to yield regurgitant volume. MR was classified as grade I when the regurgitant fraction was < 20%, as grade II when it was 20% to 35%, and as grade III to IV when it was > 35%. Thus, of the 18 hemodynamic states, 4 (from two sheep) were grade I, 7 (from five sheep) were grade II, and 7 (from three sheep) were grade III to IV. All of the velocity-distance acceleration curves showed organized acceleration fields with highly significant correlations using multiplicative regression fits (y = a.x-b, r = .90 to .99, all P < .01). Grade III to IV MR resulted in rightward and upward shifts of the velocity-distance profile curves compared with those produced by grade II and grade I MR. All of the centerline velocity-distance profiles for grade III or IV regurgitation resided in a domain encompassed by velocities > 0.5 m/s at distances from the orifice > 0.6 cm; the profiles for grade I regurgitation resided in a domain encompassed by velocities < 0.3 m/s at distances from the orifice of < 0.45 cm. The profiles for grade II regurgitations resided in a domain between them. Regression analysis for the distance at which a velocity of 0.5 m/s was first reached bore a close relation to regurgitant fraction (r = .92, P < .0001) and peak regurgitant flow rate (r = .89, P < .0001). In addition, an equation for quantitatively correlating both a and b (coefficients from the multiplicative regression fits) with the peak regurgitant flow rate (Qpeak in L/min) was derived from stepwise regression analysis: Qpeak = 12a + 2.7b-2.4 (r = .96, P < .0001, SEE = .45 L/min). CONCLUSIONS: In this study, using quantified MR volume, we demonstrate that the proximal flow convergence axial centerline velocity-distance profile method can be used for evaluating the severity of MR without any assumption about isovelocity surface shape geometry. PMID- 8205705 TI - Intimal hyperplasia, vascular modeling, and the restenosis problem. PMID- 8205706 TI - The early termination of clinical trials: causes, consequences, and control. With special reference to trials in the field of arrhythmias and sudden death. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. AB - The early termination of clinical trials, for either benefit or harm, often generates undue enthusiasm or alarm. The enhanced publicity attending early termination of a trial promotes inappropriate interpretations that are favored by the inherent difficulty of prompt and comprehensive data review. Furthermore, the process of monitoring the accumulating outcome data for early evidence of treatment benefit or harm is fraught with many statistical and methodological difficulties. This report from a task force convened by the Working Group on Arrhythmias of the European Society of Cardiology incorporates first, a series of trials terminated appropriately or inappropriately for benefit or harm and used as examples to illustrate the importance of suitable trial design and of proper stopping rules; second, a description of the committee structure of a clinical trial; third, an analysis of the general design issues; fourth, a review of the main issues in interim analysis with special reference to main strategies for reducing the rate of false-positive claims that could result from early trial termination; and finally, a series of specific recommendations concerning the design, structure, analysis, interpretation, and presentation of a clinical trial. PMID- 8205707 TI - First use of an untethered, vented electric left ventricular assist device for long-term support. AB - This report describes the first long-term (505-day) application of the vented electric (VE) HeartMate left ventricular assist device (LVAD) (Thermo Cardiosystems, Inc). The device consists of an abdominally placed, battery powered titanium blood pump that, in contrast to earlier pneumatically powered systems, allows patients untethered freedom of movement. The batteries last 5 to 8 hours and can be changed on a rotating basis indefinitely. The patient, a 33 year-old man (90 kg, blood type O) with idiopathic cardiomyopathy, experienced end-organ heart failure (New York Heart Association [NYHA] class IV) while he was awaiting heart transplantation. When his hemodynamic criteria met those outlined in the protocol, we implanted the VE-LVAD as a bridge to transplantation. The patient was supported by the device for more than 16 months. His cardiac status returned to NYHA class I, and he was eventually allowed to take day trips outside the hospital as he awaited transplantation. The VE-LVAD enabled the patient to participate in activities such as eating in restaurants, going to movies, and practicing basketball shots. Unfortunately, the patient died suddenly due to a neurological thromboembolic event that occurred on day 503 of VE-LVAD support. The VE-LVAD improved native left ventricular function by chronic unloading, and ventricular remodeling resulted in a more normal configuration anatomically, physiologically, and ultimately, histologically and pathologically. PMID- 8205708 TI - Iron stores are not associated with acute myocardial infarction. AB - BACKGROUND: This study evaluated the relation between body iron stores and coronary artery disease. It has been suggested that total body iron stores are an independent risk factor for acute myocardial infarction (AMI). METHODS AND RESULTS: Our study population consisted of 46,932 members of a prepaid health plan who were > or = 30 years old and who received a standard health check between 1969 and 1971. Blood collected during this examination was analyzed for serum iron and total iron-binding capacity. Transferrin saturation (TS), calculated as (serum iron/total iron-binding capacity) x 100, was categorized as low (< or = 10%), normal (11% to 61%), or elevated (> or = 62%). Hospital stays for AMI were identified from the health plan's computerized discharge records for its Northern California Region through December 31, 1991. Mean follow-up time was 14.1 years. During the follow-up period, 969 men and 871 women had an AMI-related hospital stay. Analysis of AMI-related hospital stays was performed overall and by sex. Age-adjusted incidence rates were obtained for each TS level, and proportional hazards regression models were used to assess the significance of TS as a risk factor for AMI, controlling for other known coronary disease risk factors. Our results did not show iron deficiency as defined by low TS to be protective against AMI. Subjects with increased iron stores indicated by TS > or = 62% had a relative risk for AMI of 1.3, which was not statistically significant. CONCLUSIONS: Our observations do not support the hypothesis that coronary artery disease risk is related to iron stores. PMID- 8205709 TI - Images in cardiovascular medicine. Profiles of sinus venosus atrial septal defect. PMID- 8205710 TI - A 56-year-old man with acute-onset pulmonary edema and shock. PMID- 8205711 TI - Reversal of coronary heart disease by lipid-lowering therapy. Observations and pathological mechanisms. PMID- 8205712 TI - Implantable cardioverter-defibrillator. Lifesaver or a device looking for a disease? PMID- 8205713 TI - Cardiovascular disease in women. PMID- 8205714 TI - VF in patients with primary electrical disease. PMID- 8205715 TI - Sidestream cigarette smoke. PMID- 8205716 TI - Aberrant ventricular conduction and ventricular ectopy. PMID- 8205717 TI - Increased aortic impedance. PMID- 8205718 TI - Menopause and blood pressure. PMID- 8205719 TI - Low iron-binding capacity: an independent heart disease risk factor? PMID- 8205720 TI - Time-dependent SCD risk during mountain hiking. PMID- 8205721 TI - Guidelines for the management of transient ischemic attacks. From the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks of the Stroke Council of the American Heart Association. PMID- 8205722 TI - Zfy is transcribed in the normal mouse epididymis and in the XXSxr ("sex reversed") testis. AB - The presence of the mutation Sex reversed (Sxr), a copy of a Y-chromosomal segment that gets transferred to an X chromosome, causes the resulting XXSxr mice to develop as apparent males. However, several features of male sexual development are abnormal in these animals. The testes are small and aspermatogenic, and the epididymides lack the initial segment. Testes and epididymides show abnormalities of extracellular matrix. In this study we examined transcription of the conserved Y chromosomal gene Zfy, which has an X chromosomal homologue (Zfx). Northern blotting showed Zfy to be expressed in the testes of XXSxr animals, except for those that carry the coat-marker gene Tabby (Ta), despite the lack of germ cells in XXSxr mice. Reverse transcription polymerase chain reaction (RT-PCR) studies detected Zfy in mRNA in testes even when Ta was present. RT-PCR also demonstrated Zfy transcription in epididymides of normal males, though not in XXSxr mice. Previous authors reported an absence of Zfy transcription in XXSxr testes; Zfy transcription in normal testes has been ascribed to germ cells. Our observation indicates that this idea requires re evaluation. The occurrence of Zfy transcription in the normal epididymis is similarly a novel finding that may help explain those aspects of epididymal development that occur in the absence of androgen. PMID- 8205723 TI - IME1 gene encodes a transcription factor which is required to induce meiosis in Saccharomyces cerevisiae. AB - Previous studies have shown that the IME1 gene is required for sporulation and the expression of meiosis specific genes in Saccharomyces cerevisiae. However, sequence analysis has not revealed the precise functional role of the Ime1 protein. By engineering constructs which express various portions of the Ime1p fused to either the DNA binding or transcriptional activation domains of GAL4, we have conclusively demonstrated that IME1 is a transcription factor, apparently required for sporulation to activate the transcription of meiosis specific genes. The full Ime1p, when fused to the GAL4 DNA binding domain, can both activate GAL1 lacZ expression, and complement ime1-0 (a null allele) for the ability to sporulate, and transcriptionally activate IME2, a meiosis specific gene. As successively larger portions of the encoded Ime1p N-terminus are deleted from the GAL4(bd)-IME1 construct, the encoded fusion proteins retain the ability to complement an ime1 null allele, despite a decreasing ability to activate GAL1 lacZ transcription. However, a fusion construct which retains only the last 45 C terminal amino acids of IME1 provides neither transcriptional activation of GAL1 lacZ nor complementation of ime1-0. Fusion of a GAL4 activation domain to this portion of IME1, results in a construct with a restored ability to complement an ime1-0 allele. This restored ability is dependent upon galactose induction. We conclude, therefore, that IME1 functions in meiosis as a transcriptional activator. PMID- 8205724 TI - Developmentally regulated expression of fibroblast growth factor receptor genes and splice variants by murine embryonic stem and embryonal carcinoma cells. AB - The expression of the four fibroblast growth factor receptor (FGF-R) genes was examined in murine embryonic stem (ES) cells, embryonal carcinoma (EC) cells, and their differentiated derivatives. FGF-R1 and FGF-R4 were found to be expressed constitutively in all samples examined. The expression of FGF-R2 and FGF-R3 was, however found to increase significantly upon differentiation of both ES and EC cells. Examination of splice variants of the third immunoglobulin domain (IgIII) of the extracellular region of the FGF-R2 revealed that whilst IgIIIc transcripts were expressed upon ES cell differentiation, IgIIIb transcripts (which confer specificity for the ligand FGF-7) were expressed in both ES cells and their differentiated progeny. FGF-R3 transcripts were also expressed in ES cells, but variant FGF-R3 transcripts containing the IgIIIb region were expressed upon differentiation. The findings suggest that the repertoire of FGF-R expression in embryonic cell types is developmentally regulated at the level of both gene expression, and alternative splicing and different members of the FGF-R family can exhibit distinct patterns of both gene and splice variant expression. PMID- 8205725 TI - Isolation of silencer-containing sequences causing a tissue-specific position effect on alcohol dehydrogenase expression in Drosophila melanogaster. AB - A transient expression assay has been used to investigate the cause of a tissue specific position effect on Adh expression from a transgene insertion in Drosophila. A 15.4-kb genomic clone containing the 3.2-kb Adh insert along with flanking regions of genomic DNA is expressed in this assay in a tissue-specific pattern resembling the abnormal expression pattern of the position effect. The 3.2-kb Adh insert is expressed normally without the flanking sequences. A silencer element is located upstream of the Adh gene within a 2-kb fragment that acts in both orientations and at a distance of at least 6.5 kb from the larval Adh promoter to suppress ADH expression in a nontissue specific fashion. The DNA sequence of the 2-kb fragment indicates that it is a noncoding region. A 17-bp sequence is repeated within this region and may be associated with the silencer activity, since subclones from the 2-kb fragment, each containing one of the repeated regions, both retain full silencer activity. This silencer fails to suppress expression from an alpha 1-tubulin promoter-LacZ fusion construct or an hsp70 promoter-Adh fusion construct. In addition to the silencer, another element is located downstream of the Adh gene that produces a higher level of anterior than posterior midgut expression. These results suggest that the 5' silencer and the 3' element act together to create the tissue specific position effect characteristic of the GC-1 line. PMID- 8205727 TI - Polyglucosan bodies in brain tissue: a systematic study. AB - The relation between age, sex and presence of polyglucosan bodies in the brain has been systematically studied in 64 patients who did not suffer from neurological brain disorders and in 2 cases with Lafora's disease. In the normal brain the number of polyglucosan bodies is related to increasing age. Under the age of 40, polyglucosan bodies can be found sporadically in cases without a neurological disorder, but in the cases of Lafora's disease their number is uncomparatively higher. A sex relation has not been found. PMID- 8205726 TI - Neocortical changes in Parkinson's disease, revisited. AB - In a series of 37 Parkinson's disease (PD) brains, cortical changes were reexamined by means of Bielschowsky silver impregnation and anti-ubiquitin immunocytochemistry. Compared to routine HE staining, anti-ubiquitin immunostaining revealed neocortical Lewy bodies (LBs) in a significantly higher percentage (76% vs. 32%). Neocortical senile plaques (SPs) occurred more frequently in brains with neocortical LBs than in cases without LBs (50% vs. 11%; p < 0.05). Semiquantitative assessment of neocortical LB density correlated with the frequency of occurrence and density of neocortical SPs. Dementia was confined to patients with abundant neocortical LBs, thus fulfilling histological criteria of diffuse Lewy body disease. We conclude that neocortical LBs are a very frequent feature of PD, although abundance of cortical LBs is confined only to a small subgroup with prominent dementia: diffuse Lewy body disease. PMID- 8205728 TI - Subacute sensory neuronopathy in small cell cancer of the lung. Immunocytochemical study of 2 cases. AB - Two cases of subacute sensory neuronopathy (SSN) associated with small cell lung cancer are reported. In both cases motor disability, attributed to motor neuropathy and neuronopathy, respectively, accompanied SSN. Immunohistochemical studies performed provide further data suggesting the involvement of humoral antibodies and the participation of protease inhibitors in the pathogenesis of SSN. PMID- 8205729 TI - Cerebral amyloid angiopathy and intracerebral hemorrhage with special reference to the pons. AB - Cerebral amyloid angiopathy accounts for approximately 10% of spontaneous intracerebral hemorrhage, typically in the cortex and subcortical white matter. Its contribution to primary pontine hemorrhage is not known. The present study was designed to determine if amyloid angiopathy occurs in the pons and whether primary pontine hemorrhages are associated with amyloid infiltration of nearby vessels. Two groups of patients were identified. Group A included 30 patients with proven CAA in whom special blocks of the pons were taken, group B consisted of 10 primary pontine hemorrhages in whom transverse blocks were available. A congo red stain and an A4 immunohistochemical technique were used. Only 1 patient from group A and none from group B had amyloid angiopathy in the pons. It is concluded that pontine angiopathy is rare and an exceptional cause of primary pontine hemorrhage. PMID- 8205730 TI - Pure thalamic dementia with a single focus of spongiform change in cerebral cortex. AB - An absence of spongiform change differentiates the pure thalamic degeneration (PTD) from the thalamic form of Creutzfeldt Jakob Disease (CJD). This report describes a case which in addition to the neuropathological changes typical of primary thalamic degeneration showed a single small focus of spongiform change in the cerebral cortex. The exceptional instances of thalamic degeneration associated with limited spongiform change among which this case is unique by virtue of the size of the single focus of vacuolation probably represent a variant of the thalamic form of CJD. In the context of potential infectious etiology the fact that the patient had a blood transfusion five months before the onset of neurological illness is of interest. PMID- 8205731 TI - Meningeal meningiomatosis in a child: case report. AB - We report a child with multifocal meningeal lesions demonstrating mixed meningiomatous histologic features. This lesion appears to have evolved over seven years, starting with a brief episode of garbled speech, nausea, and headache at 4.5 years of age. The child was then asymptomatic until 9 when she presented with bilateral leg weakness, in addition to her prior presenting symptoms and communicating hydrocephalus. Meningeal biopsies of two lesions were performed 18 months later. Immunohistochemistry and electron microscopy were needed to substantiate the histologic diagnosis. Radiation therapy to the craniospinal axis and corticosteroids were of some benefit, but more aggressive therapeutic modalities became necessary. The nosology of this lesion is discussed. PMID- 8205732 TI - Ramsay Hunt syndrome: progressive mental deterioration in association with unusual cerebral white matter change. AB - An autopsied case of Ramsay Hunt syndrome with progressive dementia was reported. The clinical symptoms included progressive intellectual decline, myoclonus, generalized convulsive seizure, cerebellar ataxia and positive pyramidal signs. Neuropathological examination disclosed cerebral white matter demyelination marked in the frontal lobe and fibrillary gliosis predominantly in the subcortical U-fibers, grumose degeneration in the dentate nucleus and inferior olivary nucleus lesion. The skeletal muscle showed no ragged-red fiber. The present case can be included in Ramsay Hunt syndrome because of the absence of pathological hallmark of mitochondrial encephalomyopathy and of the presence of the degenerative lesions in the olivary and dentate nucleus without cerebellar Purkinje cell loss. The intellectual decline is a result of extensive frontal white matter change, and myoclonus and ataxia are closely associated with dentate grumose degeneration. The cerebral white matter change is an unusual finding and the present case might be a variant in Ramsay Hunt syndrome. PMID- 8205734 TI - Leeds Dental School: conception to birth. PMID- 8205733 TI - Joint meeting of the British and Spanish Societies of Neuropathology. Barcelona, Spain, 10-11 December 1992. Abstracts. PMID- 8205737 TI - Assessment of the antidiabetic activity of Myrcia uniflora extracts in streptozotocin diabetic rats. AB - Several metabolic parameters were used to determine the evolution of the diabetic state of streptozotocin diabetic rats treated with aqueous leaf extracts from Myricia uniflora, a plant widely used in northern Brazil for treatment of diabetes. The effect of the extracts on the intestinal absorption of glucose and on the evolution of diabetes of diabetic rats adapted to a high protein, carbohydrate-free diet were also investigated. Treated rats received twice a day, by gavage, during three weeks, 7.5 mg of lyophilized powder, corresponding to about 60 mg of dried leaves, prepared from percolations with boiled water, Treatment of diabetic rats fed a stock, balanced diet did not affect body weight gain but reduced the hyperglycemia, polyphagia, polydipsia, urine volume and the urinary excretion of glucose and urea. Myrcia administration for 3 weeks had no effect on the weight of epididymal and retroperitoneal adipose tissue, or on the concentrations of pancreatic and serum insulin. The intestinal absorption of glucose, measured with a perfusion technique in situ, was markedly inhibited by Myrcia (7.5 mg of lyophilized powder per ml of perfusion solution). The effects of Myrcia treatment on diabetic rats adapted to a carbohydrate-free diet were similar to those obtained in rats fed the stock diet. The data show that aqueous extracts of Myrcia has a beneficial effect on the diabetic state, mainly by improving metabolic parameters of glucose homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205738 TI - Comparison of cartridge insulin Penmix 50:50/Isophane with soluble/Isophane in type I diabetic adolescents using a multiple injection regimen. AB - This study investigated the effect on blood sugar control and weight gain of a multiple injection therapy (MIT) regimen in 22 established adolescent diabetics using a pre-prandial 50:50 mixture of Isophane/soluble insulin with night-time Isophane. This regimen was compared in a cross-over study with MIT using pre prandial soluble insulin and night-time Isophane. After 4 wk for stabilization, there were 2 periods of 16 wk on each regimen. Throughout the study, blood sugar control was monitored by regular HbA1 and fructosamine measurements. The total daily dose of insulin was unchanged throughout the study, 1.0 +/- 0.3 iu/kg/day for Penmix/Isophane and 1.1 +/- 0.3 iu/kg/day for soluble/Isophane. The mean HbA1 and fructosamine did not alter significantly on either regimen. There was no significant weight gain during the Penmix therapy, despite the increased proportion of longer-acting despite the increased proportion of longer-acting insulin. Lean body mass (LBM) measured by skinfold thickness and electrical impedance only changed marginally on either regimen; the correlation between the 2 measuring techniques for LBM was good. Patient acceptance of the 50:50 Penmix insulin was high, 13 of 19 children preferring it to the conventional regimen. PMID- 8205739 TI - Effect of diabetic state and related disorders on the urinary excretion of magnesium and zinc in patients. AB - We examined the urinary excretion of magnesium and zinc in 175 diabetics [19 insulin-dependent (type I) and 156 insulin-independent (type II)] and in 160 control subjects of the same origin by determining the ratio of the concentration of each of these metals to that of creatinine (creat). Electrothermal atomic absorption spectrophotometry was used for analyzing Mg and Zn in urine. There was no significant difference in the urinary excretion of Mg between the control group [mean (SEM) = 362.6 (15.1) mmole of Mg/mole of creat] and the overall [350.2 (15.7) mmole Mg/mole creat], type I [368.4 (45.0) mmole Mg/mole creat], or type II [347.9 (16.7) mmole Mg/mole creat] diabetics regardless of the disorders associated with diabetes (cardiovascular diseases, neuropathy, retinopathy, infections, and hepatic disease). In contrast, diabetics of both types [2.67 (0.14) mmole Zn/mole creat] with or without a diabetes associated disorder excreted significantly (p = 0.031 to 0.0000) more Zn than did the control subjects [1.76 (0.09) mmole Zn/mole creat]. There was positive correlation between hemoglobin A1c and urinary loss of Mg (p = 0.013) or Zn (p = 0.0241) in patients with type II diabetes. From these data, it appears that of the two elements examined only Zn is associated with higher urinary loss in diabetic state. The discrepancy between our results and those of previous studies for Mg may be ascribed to dissimilarities in the diet habits and metabolism of Mg among diabetics of different geographical origins. PMID- 8205740 TI - The pharmacokinetics of five pre-mixed combinations of 'short-' and 'intermediate acting' (NPH) insulins in healthy subjects following subcutaneous administration. AB - The pharmacokinetics of five pre-mixed insulin preparations in the ratio of soluble to NPH insulin of 10:90, 20:80, 30:70, 40:60 and 50:50, were examined in a two part study in fasting healthy subjects. Each received by bolus subcutaneous injection into the anterior abdominal wall, on separate occasions one to two weeks apart, 20U of each of three pre-mixed insulin preparations in random order. In Part 1, nine subjects received Penmix 10:90, Penmix 20:80 and Penmix 30:70 and were observed over a period of 24 hours. In Part 2, eight subjects received Penmix 30:70, Penmix 40:60 and Penmix 50:50 and were observed over an 8 hr post injection period. Three subjects were common to both parts of the study. Plasma glucose, C-peptide and insulin levels were measured frequently throughout both study periods. Increasing soluble insulin content in the pre-mixtures was reflected in increasing peak plasma insulin concentrations and a greater hypoglycaemic response. There were highly significant differences between the five premixtures and preparations in the 0-4 and 0-8 hours area under the curve (AUC) values for plasma glucose, C-peptide and immunoreactive insulin concentration (p < 0.01). Whereas a gradual difference between the premixtures was seen no two adjacent ones were significantly different, however an overall highly significant difference between the five preparations tested was observed. PMID- 8205741 TI - Hemodynamic effects of lipo-PGE1 on peripheral artery in patients with diabetic neuropathy: evaluated by two-dimensional color Doppler echography. AB - Twenty non-insulin-dependent diabetic patients were studied to evaluate the hemodynamic effects of lipo-PGE1 (prostaglandin E1 incorporated in lipid microspheres). Improvement of diabetic neuropathy was assessed on the basis of subjective symptoms such as pain, coldness, numbness and dysethesia (subjective) after intravenous administration of lipo-PGE1. After lipo-PGE1 treatment, the subjective symptoms were markedly improved. Hemodynamic effects of this drug on the dorsalis pedis artery were examined using new real-time two-dimensional color Doppler echography. After administration of lipo-PGE1, the cross-sectional area of the dorsalis pedis artery significantly increased from 2.6 +/- 0.2 mm2 to 3.5 +/- 0.2 mm2 (P < 0.01). Moreover, the blood flow index significantly increased from 40 +/- 7 to 61 +/- 11 (P < 0.05). The results of this study suggest that lipo-PGE1 may serve as a useful drug in improving diabetic neuropathy. PMID- 8205742 TI - Two organizations develop new HIV early intervention guidelines. PMID- 8205743 TI - Response of plasma neuropeptide Y and noradrenaline to dynamic exercise and ramipril treatment in patients with congestive heart failure. AB - Forty-two patients with congestive heart failure were studied in order to clarify whether the plasma level of neuropeptide Y-like immunoreactivity (NPY-LI) rises in parallel with plasma noradrenaline (NA) during physical exercise in congestive heart failure (CHF). All patients were studied in a randomized placebo-controlled trial with the ACE-inhibitor ramipril during 12 weeks to determine whether ACE inhibition alters the response of plasma NPY-LI to exercise. The patients were treated with diuretics and had stable congestive heart failure (NYHA classes II III). Plasma NPY-LI was 50 +/- 5 pmol l-1 (mean +/- standard error of the mean) at rest and 60 +/- 6 pmol l-1 at the end of exercise at baseline (P < 0.01). The corresponding values for plasma NA were 2.8 +/- 0.2 nmol l-1 and 15.3 +/- 1.2 nmol l-1 (P < 0.001). Before ACE-inhibition, there was a correlation between high NPY-LI and NA values after exercise. After treatment with ramipril or placebo for 12 weeks, there was no difference in plasma NPY-LI and NA at rest or after exercise between the two treatment groups. The maximal exercise time was unchanged. It is concluded that plasma NPY-LI and NA were elevated at rest in CHF. The additional rise of plasma NPY-LI and NA after exercise was attenuated in CHF compared to healthy individuals. ACE-inhibition with ramipril did not alter plasma NPY-LI or NA at rest or after exercise compared to placebo. PMID- 8205744 TI - Stretch-induced myogenic responses of airways after histamine and carbachol. AB - The purpose of the study described here was to determine the possible role of a myogenic response of bronchial smooth muscle in deep inspiration (DI)-induced bronchoconstriction. Model experiments were performed on sheep tracheal strips. The effect of sudden stepwise elongation on isometric tension of tracheal muscle was studied in the absence and presence of the bronchoconstrictors carbachol (10( 8) M) and histamine (10(-4) M). In control strips tension increased rapidly with stretch and was followed by stress relaxation which corresponds to creep or bronchial dilatation. In histamine- and carbachol-treated strips a reactive contraction with a rhythmic pattern interrupted the process of stress relaxation. These responses appeared after only 20% elongation and were characteristic of a myogenic contraction which in the in vivo situation would correspond to a bronchoconstriction. These findings are interpreted as a functional transformation of multiple- to single-unit smooth muscle due to the influence of carbachol and histamine. This suggests that stretching (DI) of bronchial smooth muscle in the presence of carbachol and histamine induces a protracted myogenic contraction, which may explain bronchoconstriction after DI in severe asthma. PMID- 8205745 TI - Biochemical features in patients with their first acute inferior myocardial infarction. AB - Sixty eight patients with their first acute inferior myocardial infarction were studied within 24 h of the onset of chest pain by vectorcardiography and biochemical indicators. Patients were divided into three groups according to the vectorcardiographic findings: Group 1 (31 patients with inferior myocardial infarction); Group 2 (26 patients with inferior myocardial infarction and right ventricular involvement); and Group 3 (11 patients with inferior-posterior infarction). Biochemical studies showed that the tendency for the magnitude of enzyme release varied with the site inferior-posterior > inferior+right ventricular > inferior groups. However, the differences between inferior and inferior plus right-ventricular groups were not significant. This suggests that the left ventricle dominates enzyme release regardless, with or without right ventricular involvement in patients with acute inferior myocardial infarction. When the enzyme levels in inferior and inferior-posterior myocardial infarction are compared, the HBDH and CK-MB were significantly higher (2P < 0.02 and 2P < 0.05 respectively). This confirms that when the vectorcardiographic QRS loop changes are large, more enzyme is released during acute myocardial infarction. PMID- 8205746 TI - Does digital chest radiography assess regional ventilation? AB - Digital radiography of the chest was evaluated for estimation of regional ventilation disturbances. Thirty-three patients with suspected bronchial carcinomas were examined. Objective measurements of regional density changes during breathing correlated significantly with standardized regional lung function tests (133Xe ventilation scintigraphy), but did not permit reliable individual estimations of regional ventilation. About 35% of the density variations could be explained by regional ventilation. Thus, factors other than ventilation, e.g. changes in the geometry of the thorax, have a major impact on the density variation at digital radiography. PMID- 8205747 TI - Biochemical changes in relation to a maximal exercise test in patients with fibromyalgia. AB - Patients with fibromyalgia often complain of fatigue and pain during exercise and of worsening of pain days after exercise. The aim of the study described here was to determine if abnormal changes in potassium or lactate could be observed during an exercise test in fibromyalgia. Whether an abnormal incline in plasma creatine kinase or myoglobin could be observed days after the test was studied also. Fifteen female fibromyalgia patients and 15 age- and sex-matched controls performed a stepwise incremental maximal bicycle-ergometer test. Blood samples were collected from a catheter in a cubital vein. The changes in heart rate, potassium levels, and haematocrit during the exercise test were similar in the two groups. The maximal obtained lactate concentration was 4.2 mmol l-1 (3.5-5.6) in the patients as compared to 4.9 mmol l-1 (3.9-5.9) in the controls (NS). The estimated anaerobic threshold of 2 mmol l-1 was reached at a heart rate of 124 min-1 in the patients with fibromyalgia as compared to 140 min-1 in the controls (P = 0.02). In relation to workload, the patients scored higher on a Borg scale for perceived exertion during exercise, but if the Borg score was related to lactate no significant difference was found. The patients reported 86% and 79% of maximal pain in the thighs on the visual analogue scale 1 and 2 days after the test, but the creatine kinase and myoglobin concentrations were not increased. PMID- 8205748 TI - Demonstration of dilatation of peripheral airways. AB - To investigate the ability of various lung-function tests to demonstrate dilatation of peripheral airways, ten asthmatics inhaled increasing doses of a beta 2-agonist by two different and controlled techniques. Low inspiratory flow with a long post-inspiratory pause favoured peripheral deposition, and a high inspiratory flow with a short post-inspiratory pause favoured central deposition of drug in the airways. Ordinary spirometry, maximum expiratory flow rates after breathing air as well as a helium-oxygen mixture, a single breath N2-test and resistance of the respiratory system were obtained before and after each of five terbutaline doses with both inhalation techniques. By using a double-dummy technique, the study could be performed double blinded. Effects were compared at doses giving equal effects on PEF, assumed to represent equal deposition of bronchodilator and effects on central airways. At such 'iso delta PEF doses', particularly FVC and the slope of phase III of the N2-test improved more following the slow inhalation technique. It is concluded that changes in those tests reflect dilatation in peripheral airways in asthmatics. PMID- 8205749 TI - Effect of supine exercise on platelet aggregation and fibrinolytic activity. AB - In 12 healthy young men, strenuous cycling exercise in the supine position, caused platelet aggregability to decrease and the ADP threshold to rise from 7.0 microM resting, to 9.5 exercising (P < 0.01). At the same time, fibrinolytic activity increased markedly: euglobulin clot lysis time shortened from 178 to 68 min, PAI-1 fell from 8.91 to 5.16 IU ml-1, and t-PA rose from 0.56 to 3.95 IU ml 1, all three values were significant to P < 0.01. When the erect posture was assumed after lying at ease for 1 h after exercise, it did not increase platelet activity as expected, but caused a modest increase of fibrinolytic activity. These results suggest that supine exercise will not affect the haemostatic system adversely. PMID- 8205750 TI - Inhibitory effects of neuropeptide Y on splanchnic glycogenolysis and renin release in humans. AB - Neuropeptide Y (NPY) is stored in sympathetic nerves and NPY levels increase several times during exercise. NPY administration during prolonged exercise causes reduced splanchnic glucose production. To elucidate the effects of NPY on adrenaline (Adr)-stimulated splanchnic glycogenolysis these substances were infused to seven healthy subjects in the post-absorptive state. Blood samples were drawn from an arterial and a central hepatic vein catheter for determination of splanchnic blood flow, exchanges of metabolites and arterial levels of NPY, catecholamines, insulin, glucagon and renin in the basal state and during 20 min Adr infusion (0.1-0.3 nmol kg-1 min-1). After basal values were reached a 60 min NPY infusion was initiated. At 40 min of NPY infusion the Adr infusion was repeated. Adr alone increased splanchnic blood flow (41%, P < 0.01), arterial glucose concentration (29%, P < 0.001) and splanchnic glucose production (102%, P < 0.01). During the NPY infusion both splanchnic blood flow and arterial glucose fell (P < 0.05). Although the combined NPY and Adr infusion caused the same proportional increases in splanchnic blood flow, arterial glucose and splanchnic glucose production as with Adr alone the absolute values were lower (all P < 0.05). Arterial insulin as well as Adr and noradrenaline increased with the combined NPY-and Adr infusion as with Adr alone. Arterial plasma renin activity was 12% lower with the combined NPY and Adr-infusion compared to Adr infusion alone. These results indicate further an inhibitory effect of NPY on splanchnic glycogenolysis and suggest that NPY inhibits Adr-stimulated renin release. PMID- 8205751 TI - Pronounced bronchial hyper-responsiveness and asthma severity. AB - Fifty-six asthmatics from an asthma ward or from an asthma out-patient clinic were challenged with two low concentrations (0.03 and 0.012 mg) of metacholine chloride in order to assess the relationship between pronounced hyper responsiveness and asthma severity in a clinical setting. Only inhaled bronchodilators were stopped before challenge. Asthma severity was assessed retrospectively and prospectively on the basis of treatment, number of days in hospital, intensive care, number of emergency visits and days on sick-leave. The results show that pronounced hyper-responsiveness (n = 28) is not associated with asthma severity. It is concluded that a single simplified test of pronounced bronchial hyper-responsiveness, performed without taking into consideration the actual state of the disease and without stopping all medication, is of no help in identifying the patients with the clinically most severe asthma and worst prognosis. PMID- 8205752 TI - Effects of angiotensin-converting enzyme inhibition on renal dysfunction induced by moderate potassium depletion in healthy women. AB - The role of the renin-angiotensin system in renal hypokalaemic dysfunction has been investigated by evaluating the effects of the angiotensin (AT)-converting enzyme inhibition by enalapril. Healthy women were studied either in normal potassium balance (N3, n = 6) or moderate potassium depletion (KD3, n = 6). Potassium depletion (KD) was induced by low potassium dietary intake (greater than or equal to 10 mmol per day) and natriuretic treatment associated with replacement of net NaCl and water losses; the cumulative potassium deficit achieved was 214 +/- 54 mmol. The renal function and the urinary excretions of some prostanoids (PGE2, 6-keto-PGF1 alpha, TxB2) were evaluated during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis (lysine-8 vasopressin (LVP) low-dose infusion). Paired studies were performed in absence (control) and presence of enalapril. Basal plasma renin activity (PRA) and urinary aldosterone excretion were determined before the water load of control studies. Renal dysfunction typical of chronic KD occurred in the KD3 group, i.e. increase in PRA, decrease in creatinine clearance, depression of the diuretic response to water load, inhibition of distal fractional chloride reabsorption, and blunted efficacy of LVP in increasing the urinary solute concentration. The urinary prostanoid excretions were reduced. Basal urinary aldosterone excretion was not changed significantly. In KD3 group enalapril decreased mean arterial pressure (MAP), increased the plasma potassium concentration, improved the diuretic response to water load and corrected the impairment of the distal fractional chloride reabsorption. Despite the decrease in MAP enalapril did not affect significantly the creatinine clearance. Neither urinary prostanoid excretions nor the renal response to LVP were affected by the drug. The data suggest that in KD the increased activity of the renin-angiotensin system affected the renal function both through direct effects and through effects dependent on the angiotensin-supported secretions of aldosterone and probably of vasopressin. Finally, by comparing the effects of enalapril and indomethacin in experimental groups with an equivalent degree of KD, evidence is provided in favour of the interaction between renin-angiotensin and prostanoid systems in controlling the glomerular filtration rate and the salt and water handling by renal tubules. PMID- 8205753 TI - Electrocardiographic changes in stroke patients without primary heart disease. AB - Consecutive electrocardiograms were recorded in 28 stroke patients without signs of primary heart disease. Individuals with subarachnoidal haemorrhage, or electrolyte disturbances were excluded. A computerized tomography of the brain was performed in each case and showed a cerebral haemorrhage (n = 4), cortical infarction (n = 6), subcortical infarction (n = 14) and normal finding (n = 4). One patient developed atrial fibrillation but no other case of serious disturbances in rate of rhythm occurred. None developed AV block, bundle branch blocks or significant changes in QRS complexes. The most common abnormalities in ECG were transient STT changes in lateral leads, which were seen in 13 cases. The typical findings were flat or slightly negative T waves, horizontal or down sloping ST segments and sometimes a small ST depression. In no case did ECG show typical signs of acute myocardial infarction. A transient prolonged QT interval was seen in three patients and transient U waves in four. ECG did not correlate to the location of the vascular lesion seen on CT or the clinical outcome. It is concluded that STT changes of a small magnitude are seen in about half of the cases of stroke patients without primary heart disease and that they do not resemble the typical pattern of acute myocardial ischaemia. PMID- 8205754 TI - [The use of intravenous 7S immunoglobulins at high doses in HIV-related immunological pathology]. AB - 24 AIDS patients, both males and females, aged from 3 to 52 years, received high dose i.v. 7S immunoglobulin (220-400 mg/kg, range 7.5-20 g/die). These patients were affected by HIV-related thrombocytopenia and antibiotic-resistant severe hyperpyrexia; three HIV-positive asymptomatic children with severe immunodeficiency were treated to prevent opportunistic infections. I.V. 7S immunoglobulins were well tolerated, and were found to be very effective in the therapy of thrombocytopenia and in the prevention of opportunistic infections in the asymptomatic children. PMID- 8205755 TI - [The efficacy of creatine phosphate in the treatment of patients with heart failure. Its echographic evaluation after acute and protracted treatment]. AB - The hemodynamic effects of acute and long-term administration of creatine phosphate were studied in 23 patients with heart failure (NYHA classes II and III) under stabilized treatment. Acute creatine phosphate (5 g i.v.) induced a significant increase of the ejection fraction (FE) and of other parameters of cardiac contractility. Once these improvements of cardiac contractility were obtained by acute treatment, further significant increases in cardiac function were observed if treatment was continued for six days, i.e. telesystolic diameter and volume, as well as parietal stress were significantly reduced, and ejection fraction and shortening fraction were significantly increased. Creatine phosphate treatment has a favourable influence on the hemodynamics of patients with an obvious contractility deficit and chronic ischemia of the myocardium. PMID- 8205756 TI - [The use of verapamil in the treatment of hemicrania without aura]. AB - The efficacy of verapamil CR in migraine prophylaxis has been tested in an open study with 64 patients. The group of patients showed a significant decrease of the frequency, duration and severity score of their headache. All patients were treated for 3 months; thirty patients extended the treatment for 6 months without further improvement. In conclusion, verapamil CR is a useful drug with few side effects for migraine prophylaxis. PMID- 8205757 TI - [The therapeutic prospects of ischemic cardiopathy]. AB - Having thoroughly reviewed the risk factors and pathophysiologic features of ischemic heart disease, the authors describe therapeutic protocols at present in use and take stock of the perspectives opened by new drugs with different kinetic and dynamic and more advanced properties compared to those at present in use. PMID- 8205758 TI - [Osteoporosis. The recent findings on its etiopathogenesis, diagnosis and therapy. II. Therapy]. AB - Management of osteoporosis has as yet a number of aspects that are not well understood and at times even contradictory, also in view of the fact that some physicians have their "personal therapeutic approach". While on the one hand, the US FDA recognizes calcium, estrogens and calcitonin as the sole remedies for osteoporosis, on the other a variety of drugs have been studied and are at present in use. Among the drugs considered are those apt to reduce bone resorption (calcium, vitamin D metabolites, estrogens, calcitonin, diphosphonates, and ipriflavone) and those favouring bone formation (fluorides, anabolic androgens, PTH and ipriflavone). In addition, future approaches to osteoporosis therapy are considered which may make use of anti-interleukin 1 and 6, as well as of growth factors with specific osteotropism. At present, the physician must know what types of treatment are available for the individual patient with osteoporosis and be able to evaluate the cost/benefit ratio of each drug together with its side effects. PMID- 8205760 TI - [The chronic fatigue syndrome]. PMID- 8205759 TI - [Intraperitoneal chemotherapy]. PMID- 8205761 TI - The role of individual psychotherapy in the treatment of major depression. PMID- 8205762 TI - Clinical patterns of ADHD: a treatment model based on brain functioning. PMID- 8205763 TI - Internal carotid artery sacrifice. AB - Sacrifice of the ICA can be used to treat a variety of conditions. Whenever possible, temporary occlusion of the carotid artery should be performed before the actual sacrifice to evaluate for tolerance to the occlusion. In many cases, endovascular occlusion of the carotid artery is preferable to surgical occlusion. PMID- 8205764 TI - Diagnosis and management of bipolar II disorder. PMID- 8205765 TI - Psychologic principles of substance abuse: a brief overview. AB - In this paper, a brief overview of the psychology of addictions was presented. It was emphasized that physicians should initiate treatment by first diagnosing their addicted patients with "substance dependence." This paper also emphasized the significance of relapse and relapse prevention, and a model of motivation and behavior change was presented. CT was described as a useful approach for understanding the psychology of addictions. And finally, the treatment of addictions was briefly discussed. PMID- 8205766 TI - The genetic epidemiology of schizophrenia. PMID- 8205767 TI - Seizure disorders: syndromes, diagnosis, and management. PMID- 8205768 TI - Sleep apnea. PMID- 8205769 TI - Divorce sequelae in clinical practice. PMID- 8205770 TI - Common errors in the pharmacologic treatment of drug dependence and withdrawal. PMID- 8205771 TI - Time-accuracy functions for determining process and person differences: an application to cognitive aging. AB - A paradigm for the determination of time-accuracy functions (TAFs) for individual participants is introduced for two pairs of tasks differing in cognitive complexity, that is, word scanning vs cued recognition and figural scanning vs figural reasoning. TAFs can be used to test dissociations of cognitive processes beyond scale-related ambiguities of ordinal interactions. The approach is applied to examine the cognitive-aging hypothesis that a single slowing factor can account for interactions between adult age and cognitive task complexity. Twenty young and 20 old adults participated in 17 sessions. Presentation times required for 75, 87.5, and 100% accuracies were determined for each task with a variant of the psychophysical method of limits. Accuracy was fit by negatively accelerated functions of presentation time. State-trace analyses showed that different slowing factors are required for high- and low-complexity tasks. Relations to speed-accuracy and performance-resource functions are discussed. PMID- 8205772 TI - The illusory transparency of intention: linguistic perspective taking in text. AB - Subjects read scenarios where a speaker made a comment that, depending on information that was privileged to the subjects, could have been interpreted as sarcastic or not sarcastic. Their task was to take the perspective of an uninformed addressee and determine whether he or she would perceive sarcasm. Overall, when subjects believed that the speaker was actually being sarcastic they were more likely to attribute the perception of sarcasm to the addressee- even when the message was conveyed in writing and could not have involved disambiguating cues such as intonation. Data from four different experiments suggest that readers do use information that is perspective-irrelevant and thus pose a problem for theories of language use that assume readers only use "relevant" information. PMID- 8205773 TI - Allocation of dental caries prevention in Swedish teenagers. AB - In this study, the hypothesis that teenagers with high caries activity on proximal surfaces receive more preventive care in the Swedish Public Dental Health Service than those with lower caries activity on these surfaces, was tested in an audit study. Dental records and bitewing radiographs from 1987 and 1991 were used to assess caries progression in 406 teenagers from the age of 13 to the age of 17. The time allocated to prevention during the period was also registered. Caries progression as a measure of disease activity was tested. The results showed that the hypothesis could not be verified. The Odds ratio was 1.35, indicating that the chance to get more than 15 min preventive time during 4 yr was only 1.35 times higher if you were highly caries active than if you were less caries active. Although the reproducibility of the method to use caries progression as a measure of disease activity was not high, it was considered a better indicator of active disease than the number of DMF surfaces. PMID- 8205774 TI - Periodontal status in an urban adult population in Sweden. AB - The purpose was to describe the current periodontal status in a Swedish urban population aged 31-40 yr. 1681 individuals, 840 men and 841 women, participated in the study. 68.5% of the subjects had low amount of plaque, 82.8% low level of calculus and 28.9% healthy gingiva or mild gingivitis. 82.8% of the subjects had no pockets with probing depth (PD) > or = 5 mm. 4.9% of the subjects had one tooth with PD > or = 5 mm, 6.7% 2-5 teeth, 2.4% 6-9 teeth and 3.2% > or = 10 teeth with pockets. 55.8% of the subjects had no missing teeth, third molars excluded. 16.5% had one tooth missing, 23.8% 2-5 teeth, 2.7% 6-9 teeth and 1.2% > or = 10 teeth. 8.6% of the subjects had at least one front tooth missing, 28.7% one premolar and 24.1% one molar missing. Men had significantly higher scores than women for plaque (DI-S), calculus (CI-S), gingivitis (GI-M), and number and percent of remaining teeth with PD > or = 5 mm. Smokers had significantly higher scores than non-smokers for DI-S, CI-S, GI-M, number and percent of remaining teeth with PD > or = 5 mm, and number of missing teeth. The individuals who visited the dentist every year had better oral hygiene and gingival status than those who attended for > 3 yr. The multiple regression analysis showed that calculus (P = 0.0001) smoking (P = 0.001), and dental visits (P = 0.0284) were significantly correlated to the number of teeth with PD > or = 5 mm. PMID- 8205775 TI - Views of dental patients about the education and practice of dentists. AB - The opinions of 253 adult U.K. dental patients were sought as to the scope of dental education. Most appreciated this was a university education and that it exceeded 3 yr. Nearly one half believed that apprenticeship was involved and one quarter believed that postgraduate experience in hospital was mandatory. Few acknowledged the wide breadth of training and a majority would consult a physician rather than a dentist regarding problems such as oral ulceration. PMID- 8205776 TI - Prevalence of dental fear in Brazilian high school students in Sao Paulo state. PMID- 8205777 TI - Early-onset periodontitis in Hispanic-American adolescents associated with A. actinomycetemcomitans. AB - This study examines the frequency of oral disease in an adolescent population, and assesses the relationship to Actinobacillus actinomycetemcomitans. A total of 470 eighth grade students from San Antonio, Texas, were examined clinically for number of teeth, frequency of gingival inflammation, frequency of sites with BOP, and frequency of sites with 3-5 mm pockets, and pockets > 5 mm. The population ranged in age from 12 to 17 yr and was 93% Hispanic. Heavy accumulations of plaque and calculus were frequently observed and were associated with gingival inflammation, as 95.6% of the students exhibited bleeding on probing, and 99.6% of the students presented with at least on quadrant of inflammation upon visual examination. Significantly, 25.7% of the students exhibited early-onset periodontitis (EOP) with 1.7% diagnosed as LJP. Many students exhibited substantial levels of plaque and calculus, but no clinical evidence of loss of attachment. Subjects with periodontitis (EOP or LJP) presented with elevated systemic IgG antibody to A. actinomycetemcomitans serotype b and subgingival plaque samples positive for the microorganism. These results describe the prevalence of EOP/LJP in an adolescent Hispanic population from South Texas. The findings support that A. actinomycetemcomitans may represent a pathogen in periodontitis and while oral health care may be poor, contact with the microorganism appears to be required to initiate disease in this population. PMID- 8205779 TI - Multifactorial modeling for root caries prediction: 3-year follow-up results. AB - The study was part of a series aiming at the development of caries tests. The initial material (n = 104, age range 47-79 yr, mean 62 yr) was reduced to 96, who were observed for 3 yr. During the follow-up four subjects died, all due to myocardial infarction, and four refused to participate. Thorough oral examinations were conducted at the baseline, 1- and 3-yr registrations; coronal and root surface caries were registered separately according to WHO classification. The tests included salivary mutans streptococci, lactobacilli, candida/yeasts, secretion rate, buffer effect and sucrase activity, and quantitation of visible plaque. The association between prospective root caries increment and several tests was significant. Multifactorial modeling resulted in the combination of Past Root Caries Experience (OR 12.8), Lactobacilli (OR 8.6) and Candida (OR 2.8). At screening, the criterion "two or three positive tests" of these yielded acceptable accuracy (77.1) and a relative risk of 3.3. PMID- 8205778 TI - Effect of fluoride in amalgam on secondary caries incidence. AB - Caries incidence is falling in many developed countries but is believed to be increasing in developing countries. Insofar as treatment for caries is provided, ordinary amalgam restorations are usually the standard choice. These carry a risk of failing due to secondary caries. The aim of this study was to compare the occurrence of secondary caries adjacent to fluoride-containing amalgam with that adjacent to a conventional amalgam under field conditions in Bahrain. Children (n = 415) aged 6-14 yr who required occlusal restorations in two homologous contralateral permanent molar teeth were identified. Using the split-mouth design, one tooth received a fluoride-containing amalgam filling and the other a conventional amalgam restoration. A random method was used to determine which type of filling was placed on each side. After 4 yr, 357 children were still available for examination; of these 5 had to be eliminated from analysis for various reasons. Of the 704 teeth in the analysis, secondary caries had occurred in 135 (86 conventional amalgam, 49 fluoridated amalgam). By comparison with the conventional amalgam, the effectiveness of the fluoride amalgam was 43% (95% C.I. 24.4%, 57.1%) and the net gain 10.3% (95% C.I. 4.75%, 16.3%). The relative risk was 0.570 (95% C.I. 0.444%, 0.731%). Since fluoride amalgam has identical handling properties to conventional amalgam, performs similarly under clinical conditions and costs about the same, it should be the amalgam of choice for restorations in communities where the incidence of secondary caries is high. PMID- 8205780 TI - Assessment of states of dentures and interest in implant-retained prosthetic treatment in 55-year-old edentulous Finns. AB - One hundred and fifty 55-year-old edentulous subjects (104 women and 46 men) were interviewed. Materials, conditions, functional stabilities, and occlusions of complete dentures, and resorption of alveolar crests were recorded and assessed. The dentures were in good condition in 52% of subjects. Occlusion was correct in 45% of cases. Every fifth mandibular denture exhibited good functional stability. The mean age of dentures in good condition and functionally stable was statistically significantly lower than the mean age of dentures poor in these respects. Severe alveolar resorption contributed to poor functional stability of dentures (P = 0.0068 (maxilla), P = 0.0023 (mandible)) and to incorrect occlusion (P = 0.0177). Good agreement was noted between objective and subjective opinions of denture function (P = 0.01 (maxillary denture), P = 0.01 (mandibular denture)). Although oral rehabilitation with endosseous implants is common and, objectively, needs for such treatment existed, only 22 subjects (15%) who had recently had their dentures renewed and were experiencing problems with functional stability were interested in implant-retained overdentures. PMID- 8205781 TI - A comparative study of costs for dental services and dentists' income in the United States and Norway. AB - The United States and Norway have approximately the same per capita Gross Domestic Product (GDP) and average personal income, but their per capita health spending patterns are quite different. In 1982, the US spent 6.5% of its total health expenditures on dental services while Norway spent 5.4%. A higher percentage of Norwegian adults see a dentist annually as compared to US adults. In 1984, the mean net income of dentists in private practice was $66,940 in the US and $27,125 in Norway; this is respectively 5 and 1 3/4 times the average per capita income in those countries. The American publicly-employed dentist earned approximately two-thirds of what the American private practitioner made, while still earning approximately 50% more than his Norwegian counterpart. Some basic information concerning the ratios of dentists, specialists, and dental hygienists to the population is given. The relative proportion of women dentists in the two countries is contrasted. Finally, data on graduates from the dental schools, enrollment cuts, and estimated dentist to population ratios by the year 2000 are described to compare future manpower that will be available to the two countries. Several dissimilarities in the political and social systems are described and discussed. It is emphasized that caution should be used when interpreting and comparing data about countries with different dental delivery, political, and social systems. PMID- 8205782 TI - Relationship between dentists' treatment attitudes and restorative decisions made on the basis of simulated bitewing radiographs. AB - The implicit valuations which dentists place on the outcomes of their treatment decisions may be a major contributory factor in dentists' decisions about when to restore teeth. This study sought to examine the relationship between dentists' treatment attitudes and restorative dental treatment decision making. A group of 20 dentists were asked to indicate teeth in need of filling from 15 simulated bitewing radiographs. The dentists graded their level of certainty about their treatment decision as "definite", "probable" or "possible". Afterwards, the teeth were sectioned and examined using a microscope in order to determine how far through the tooth the caries had penetrated. The gold standard treatment criterion was that caries extending into the dentine of the tooth would require restoration. Receiver Operator Characteristic (ROC) analysis was used to examine the apparent weighting the dentists were giving to decision errors when planning treatment on the basis of bitewing radiographs. The dentists also completed a treatment attitudes questionnaire to determine their views about the relative importance of false negative and false positive treatment decisions. The results suggest that the most appropriate operating point for most of these dentists to achieve an outcome which matched their views about the relative importance of the two types of treatment error would be the point at which a filling would "definitely" be required. PMID- 8205783 TI - Restorative caries treatment patterns in Danish 20-year-old males in 1986 and 1991. AB - This study examines the restorative caries treatment pattern in Danish 20-year old military conscripts in 1986 and 1991. The study groups comprised 85 and 164 males born in 1966 and 1971, respectively. The examination was performed as a part of the routine for each conscript according to directions from Dental Service, Danish Defense Forces and included surface recording of fillings on all teeth except third molars. Two bitewing radiographs were taken of all conscripts in the 1986-group and of those who gave permission (59) in the 1991-group. The mean number of filled surfaces was 10.2 and 8.8 in 1986 and in 1991, respectively. 80% of the occlusal surfaces on permanent first molars were filled in the 1986-group and filled or sealed in the 1991-group in contrast to 45% of permanent second molars. Data from maxillary molars indicated a tendency to placement of fillings related to tooth specific morphology whereas extended fillings involving the entire occlusal surface dominated on mandibular molars. The X-ray examination disclosed that the majority of approximal molar surfaces were classified as sound in both study groups. Less than 1% of the approximal molar surfaces were recorded as having lesions penetrating deep into the dentin. In 1981 and in 1986 the participants in the study groups were 15 yr old. In these years the mean number of filled surfaces in Danish children amounted to 11.0 and 6.9 respectively, which indicates that very few lesions in need of operative treatment developed from age 15 to age 20 in both study groups. PMID- 8205784 TI - Evaluation of an area-based measure as an indicator of inequalities in oral health. AB - The literature on inequalities in health provides convincing evidence that lower socioeconomic groups have poor oral health when compared to higher socioeconomic groups. Since conventional measures of socioeconomic status such as occupation, income and education have a number of weaknesses which may limit their ability to describe and explain health inequalities, alternatives in the form of area-based measures are increasingly being used. In this paper, a conventional measure, household income, and an area-based measure of socioeconomic status are compared in terms of their ability to identify inequalities in oral health. The data used in the analysis were taken from a telephone interview survey of the oral health of older adults in the province of Ontario, Canada. While household income proved to be a marginally better predictor of these inequalities than the area-based measure, the latter had a number of distinct advantages from an epidemiological and planning perspective. Moreover, it identified variations in measures of oral health that were independent of household income, and the region of the province in which subjects lived. PMID- 8205785 TI - Clinician's ability to identify caries risk subjects. AB - The clinician's ability to identify caries risk children without saliva tests was studied in five health care centers. 77 examiners predicted, after the annual check-up and treatment, whether, during the following 12 months, the child would develop new dentinal caries lesions to be filled. 7917 children aged 5-16 yr were included. Only information routinely available at clinical examinations was used. In general, the overall sensitivity was 44% and specificity 90%. Some clinicians were able to identify the caries risk children with high sensitivity and specificity figures. PMID- 8205786 TI - Oral health status among schoolchildren in Romania, 1992. AB - In Romania, systematic information on the occurrence of oral diseases in children is scarce. The purpose of the present study was to describe the prevalence and the pattern of dental caries in schoolchildren, and to use the data to provide a baseline for planning and evaluation of oral health care. A national sample of children at grade 1 (n = 729) and grade 6 (n = 660) was chosen consistent with the WHO pathfinder principle. Clinical examinations were carried out according to the recording system for the Danish Municipal Dental Service and the following results were obtained. In children of grade 1 (7-yr-olds) the prevalence proportion of caries in primary teeth was 86% and in permanent teeth 39%. The mean caries indices were 11.4 defs and 1.3 DMFS. At grade 6 (12-yr-olds) the prevalence proportion of caries in primary teeth was 17% and in permanent teeth 90%. The mean caries experience was 0.8 defs and 6.5 DMFS, and a mean of 4.1 DMFT was observed. In both groups, the D-component of the caries index was dominant. The children were also classified by caries severity zone. At grade 1, 61% had a very severe pattern of caries in the primary teeth, i.e. caries in pits/fissures, proximal surfaces, smooth surfaces, and incisors. Forty-three percent of the children at grade 6 showed this pattern in permanent teeth. In Romanian schoolchildren the present level and pattern of dental caries are most severe and the implementation of oral health promotion and prevention at the community level is urgently needed. PMID- 8205787 TI - Dental caries in preschool Beijing and Connecticut children as described by a new caries analysis system. AB - A total of 625 children, 3-4 yr old, 426 from Connecticut Head Start programs and 199 from Beijing area nursery schools, were clinically examined for dental caries. Results were analyzed using the traditional dmfs index as well as a new "Caries Analysis System". This new system differentiated between caries patterns and examined the percentage of affected children (Prevalence), the degree to which these children were affected (Severity) and the proportion of total caries each disease pattern represented (Distribution). The Caries Analysis System revealed differences in caries experience and patterns among the racial/ethnic groups that the dmfs index did not. The Beijing children experienced the greatest Prevalence of all caries patterns; however, the Severity and Distribution of the caries patterns were similar to those of the Connecticut children. Within the group of Connecticut children, White children had the lowest Prevalence but the greatest Severity when compared with the Black and Hispanic children. PMID- 8205788 TI - The computational restoration of autoradiographic images. AB - A double integral formula is derived for the distortion in an autoradiographic image due to electron "cross-fire", and a deconvolution procedure for image restoration using a fast Fourier transform algorithm is developed. The technique is applied to a simulated autoradiograph of a uniform disc source and is found to give excellent results. Further image enhancement is obtained from the use of a spatially moving average smoothing process. PMID- 8205789 TI - Pattern recognition and interpretation of electromyogram data from cat jaw muscle. AB - This study investigates the effect of emotional behavior on the masseteric muscle EMG response patterns. Two experimental protocols are utilized: (1) does not elicit emotional behavior (stick chewing) and (2) elicits emotional behavior (hypothalamic stimulation). The Karhunen-Loeve transform is used to compute features which exactly represent the correlated patterns of mean-zero observations, with data compression and noise immunity. Using nonparametric tests, it is found that the populations of biting and hissing features are significantly different (p < 0.05), with increased statistical significance as the size of the training set is increased. No statistically significant difference is seen in a test of the two biting populations. PMID- 8205790 TI - A model for analyzing the formation of thrombin in vessels. AB - A pseudo steady-state model is proposed to analyze the effects of a vessel length, blood-flow velocities, and the concentration levels of Va/Xa/phospholipid complex on the formation of thrombin in an arterial vessel. The outlet concentrations of thrombin are calculated in either physiological or pathological coagulation process. Among those factors, blood-flow velocity is the most important factor which affects the amount of thrombin formation. The model and its results might be used as a reference for those who clinically manage coagulation problems of patients with severe sepsis. PMID- 8205791 TI - PCDOSE: an interactive software system to calculate internal radiation dose on a personal computer. AB - An interactive, menu directed, software system to calculate committed dose equivalents for individuals with different physiques after inhalation, ingestion or injection of radionuclides has been developed. The calculations are based on ICRP 26/30 methods. The programs are written in PASCAL and can be implemented on a personal computer with a MS-DOS operating system and a hard disk with a storage capacity of at least 20 Mb. This paper describes the development and features of the system. PMID- 8205792 TI - A computerized acquisition technique for the Wingate anaerobic test. AB - This paper describes a computerized system for the administration of the Wingate anaerobic test. The rate of pedal revolutions on a cycle ergometer is measured automatically to determine the maximal anaerobic capacity, total energy output and decline of power output over time. The system is cost effective, provides high accuracy and is incorporated into a fitness-analysis system that allows the user to recall and print present and past test results for the monitoring of anaerobic performance. PMID- 8205793 TI - Comparison of AR-based algorithms for respiratory sounds classification. AB - Respiratory sounds of pathological and healthy subjects were analyzed via autoregressive (AR) models with a view to construct a diagnostic aid based on auscultation. Using the AR vectors, two reference libraries, pathological and healthy, were built. Two classifiers, k-nearest neighbour (k-NN) classifier and a quadratic classifier, were designed and compared. Performances of the classifiers were tested for different model orders. The best classification results were obtained for model order 6. PMID- 8205794 TI - Parasitology tutoring system: a hypermedia computer-based application. AB - The teaching of parasitology is a basic course in all life sciences curricula, and up to now no computer-assisted tutoring system has been developed for this purpose. By using Knowledge Pro, an object-oriented software development tool, a hypermedia tutoring system for teaching parasitology to college students was developed. Generally, a tutoring system contains a domain expert, a student model, a pedagogical expert and the user interface. In this project, particular emphasis was given to the user interface design and the expert knowledge representation. The system allows access to the educational material through hypermedia and indexing at the pace of the student. The hypermedia access is facilitated through key words defined as hypertext and objects in pictures defined as hyper-areas. The indexing access is based on a list of parameters that refers to various characteristics of the parasites, e.g. taxonomy, host, organ, etc. In addition, this indexing access can be used for testing the student's level of understanding. The advantages of this system are its user-friendliness, graphical interface and ability to incorporate new educational material in the area of parasitology. PMID- 8205795 TI - An algorithm for estimating the terminal half-life in pharmacokinetic studies. AB - An algorithm is developed for automating the process of identifying the terminal phase in plasma concentration-time curves for non-compartmental estimation of the terminal elimination rate and half-life. The manual process of plotting each curve, selecting the observations in the terminal phase, performing the regressions and plotting the fitted regression lines can be very time-consuming in cases where many curves are to be processed. The algorithm makes use of single row regression diagnostics to determine the first observed time point in the terminal phase. An example is used to illustrate the calculations, and a simulation study was conducted to evaluate the performance of the algorithm. The algorithm has been implemented in a computer program. PMID- 8205796 TI - An algorithm for assessment of fracture displacement and pin positions in femoral neck fractures. AB - A method for determination of both the displacement of the femoral head and the position of the fixation device in fixed femoral neck fractures is described. In routine AP and lateral radiographs of the hip, measurements are made of femoral neck-shaft angle, the diameter of the femoral head and neck, the distances from the center of the femoral head to the femoral neck axis and the distances from the femoral neck axis to the fixating screws. From these values the position of the femoral head and the fixating screws are determined by geometric calculations. A computer program in Q-BASIC was devised to perform the calculations and to produce graphic displays of cross-sections of the femoral head and neck, with the displacement of the head and the screw positions indicated. The accuracy of the method was evaluated by a new method using axial radiographs of hip specimens, which were compared with the computer-plotted graphs of the femoral head and neck. The mean error of the method was found to be +/- 5% of the femoral head diameter, approximately 2.5 mm. PMID- 8205797 TI - A program for measuring timing and accuracy in a complex motor reaction task. AB - A program was developed to explore a subject's accuracy and response timing in a reaction-time paradigm, which involves a multiple choice along with a complex response. The program can be run on an IBM-PC or compatible computers. The subject's task is: (1) to react to a stimulus (task) pattern by releasing a go key (release time); the pattern is displayed on a keyboard as a combination of up to five light-emitting diodes associated with five answer keys; (2) then to press correctly the key combination indicated (response completion time). The keys are located at positions corresponding to finger tips. The response is complete at the moment all keys of the required combination are held down simultaneously, the order in response completion is not important. Responses are classified according to possible errors: whenever a key is pressed that does not belong to the required combination or the full key combination is not held until a (preset) waiting time period, the response is classified as incorrect. Various task patterns representing the required response combination of any subset of the five keys can be designed. Both the left and the right hand can be tested separately. In this way, possible distortions in performance caused, for instance, by apraxia can be analyzed. Basic statistical characteristics of the release times and completion times for correct responses are computed from the data and stored. The program is written in MODULA-2, the output files are in the ASCII format, which enables further processing of the data by standard statistical packages. PMID- 8205798 TI - Analyzing the performance of diagnostic tests. AB - When a single diagnostic test is used to assess the disease state of a patient, the classic univariate measures of sensitivity and specificity are used. When combining two or more diagnostic tests, other methods provide alternative methods for assessing the utility of combining these tests. We have written and tested a program in FORTRAN that computes the univariate statistics and bivariate concordant/discordant statistics analyses of all possible combinations of diagnostic tests as compared with the 'gold standard'. PMID- 8205799 TI - The design and construction of a medical simulation model. AB - This paper describes the design, construction and validation of a probabilistic simulation model of patients who present with abdominal pain. The model incorporates text-book medical knowledge, clinical judgment, and statistics collected from real cases. The knowledge representation combines techniques of Bayesian network modelling with ideas of logistic discrimination. The model is shown to generate convincing, realistic cases; large numbers of artificial cases with no missing observations can be generated quickly. This should make the model a useful tool for investigating factors which limit achievable computer accuracy in the diagnosis of abdominal pain. PMID- 8205800 TI - A veterinary anatomy tutoring system. AB - A veterinary anatomy tutoring system was developed by using Knowledge Pro, an object-oriented software development tool with hypermedia capabilities, and MS Access, a relational database. Communication between them is facilitated by using the Structured Query Language (SQL). The architecture of the system is based on knowledge sets, each of which covers four different descriptions of an organ, namely gross anatomy (general description), gross anatomy (comparative features), histology, and embryology, which constitute the knowledge units. These knowledge units are linked with three global variables that define the animals, the topographies, and the system to which this organ belongs, creating three data bases. These three data-bases are interrelated through the organ field in order to establish a relational model. This system allows versatility in the student's navigation through the information space by offering different modes for information location and presentation. These include course mode, review mode, reference mode, dissection mode, and comparison mode. In addition, the system provides a self-evaluation mode. PMID- 8205801 TI - PANSYM: a symbolic equation generator for mathematical modelling, analysis and control of metabolic and pharmacokinetic systems. AB - Software is presented for automatic generation of first-order ordinary differential equations (ODE) that arise from lumped parameter representations of metabolic and pharmacokinetic systems. The definition of system structures is accomplished by fractional transfer rates between state variables, together with input/output equations and initial conditions of state variables. General non linear mathematical expressions can be assigned to all structure definition items. The software parses and interprets the system definitions and generates symbolically the mathematical expression of the model's set of ODE. In addition, symbolic derivatives of state equations are determined with respect to model parameters, state variables and external inputs. These derivatives represent the constituents of systems of sensitivity-differential and adjoint-differential equations that arise in identification and optimal control problems. Finally, output routines generate source code that, once compiled and linked to simulation programs, allows efficient numerical integration of the system of ODE. This software has been developed in PROLOG on Macintosh computers and has been extensively used with the programming environment MATLAB. Possible applications of this software include model building, sensitivity analysis, identification, optimal experiment design and numerical solution of optimal control problems. PMID- 8205802 TI - Estimating sample sizes for repeated measurement designs. AB - Formulas for estimating sample sizes that are required to provide specified power for analysis of variance (ANOVA) tests of significance in a two-group repeated measurements design are presented and evaluated. Power and sample size requirements depend on the pattern of treatment effects and the pattern of correlations among the repeated measurements, as well as on parameters common to sample size estimation for cross-sectional comparisons of treatment effects in simple randomized designs. Simplifying assumptions permit generation of these numerous parameter estimates from predictions of the magnitude of the standardized "effect size" at end of trial and the single correlation between the baseline and endpoint measurements. Monte Carlo methods are used to verify the actual power of different tests of significance for treatment effects in repeated measurement designs using sample sizes estimated by the formulas. The sample size implications of different patterns of treatment effects, levels of correlation, and numbers of repeated measurements are evaluated. PMID- 8205803 TI - Extension of one-sided test to multiple treatment trials. AB - In a two-treatment clinical trial, a one-sided test is sometimes used in reaching a decision. Usually we are interested in doing a one-sided test because of the existence of an unequal preference between the two treatments. When a standard control is just as good or better than the new experimental treatment (which has more toxicity or cost), we will stay with the standard control. In this paper, we extend the concept of a one-sided test to the multiple treatment trial where three or more treatments are involved. We assume that there is an order of strictly decreasing preference among the treatments. We propose two multiple-step decision procedures that are similar to the bubble sorting algorithm and will guarantee a high probability of finally selecting the correct treatment. We also provide methods to calculate the sample size required to detect a specific difference. The derivation is based on normal data, and the extension to binomial or exponential data with random censoring is through large sample approximation. PMID- 8205804 TI - A comparison of two methods of estimating a common risk difference in a stratified analysis of a multicenter clinical trial. AB - In this paper, we compare two methods of estimating the difference between the proportion of adverse events in a test treatment group and the proportion of adverse events in a control treatment group in a multicenter clinical trial. We used simulated data to compare the bias and mean squared error of the weighted least squares estimator to the bias and mean squared error of the Cochran-Mantel Haenszel estimator. We also computed the coverage probabilities for confidence intervals derived from these estimators. We found that the weighted least squares method was often seriously biased. The coverage probabilities for the Cochran Mantel-Haenszel estimators were often closer to their nominal values than were the coverage probabilities for the weighted least squares estimators. It also was found that these methods require a larger sample size to maintain coverage probabilities near their nominal values when unequal numbers of persons are assigned to the test and control treatments. PMID- 8205805 TI - Recruiting hard-to-reach subjects: is it worth the effort? AB - Little information is available on the utility of spending resources to recruit hard-to-reach subjects. In particular, the compliance of such subjects with study protocols and visit schedules has not been documented. We present recruitment data from a two-phase survey of asthma prevalence in which a subset of respondents to a brief screening survey was recruited to attend a 90-min clinic visit. Although 39% of phase I subjects responding to initial contact attempts participated in the second phase of the study, this dropped to 12% among those responding to the sixth contact attempt (a phone follow-up). In studies in which the representatives of the sample is not of paramount importance, we see little benefit in aggressively seeking to recruit hard-to-reach subjects. PMID- 8205806 TI - Issues in the mortality analysis of randomized controlled trials of cancer screening. AB - This paper is concerned with the analysis and interpretation of randomized controlled trials (RCTs) of periodic screening programs for the early detection of cancer in which there is a lengthy follow-up period without screening being offered. That is, screening is offered for a limited time with a subsequent follow-up period during which the cancer mortality is observed. The paper focuses on tests for a mortality reduction due to screening. Two approaches are presented, one based on the experience of all those randomized to the test and control groups, and the other based on the experience of selected groups of cancer cases found during the trial. In the latter approach it is necessary that the two groups selected for analysis be comparable groups of cancers. The concept of comparability is discussed with emphasis on factors that determine comparability and on ways to assess it. Examples from completed cancer screening RCTs are used to illustrate the ideas and methods presented. PMID- 8205807 TI - Comparison of inspiratory work of breathing between flow-triggered and pressure triggered demand flow systems in rabbits. AB - OBJECTIVES: Flow-triggered continuous positive airway pressure decreases the inspiratory work of breathing in adults when compared with pressure-triggered continuous positive airway pressure. However, the effect of flow-triggered continuous positive airway pressure on work of breathing in neonates is not known. Our objective was to determine if flow-triggering was superior to pressure triggering in the presence of narrow endotracheal tubes, such as those tubes used in neonates. DESIGN: Prospective evaluation using within-animal comparison of flow-triggering and pressure-triggering demand flow systems. SETTING: The animal laboratory in a university hospital. SUBJECTS: Six spontaneously breathing white rabbits, tracheostomized and intubated with 3- and 4-mm inner diameter endotracheal tubes. INTERVENTIONS: The animals were connected to a ventilator through a standard respiratory circuit. The ventilator was randomly operated in the following modes: flow-triggered continuous positive airway pressure, pressure triggered continuous positive airway pressure, flow-triggered with 5 cm H2O pressure support ventilation, and pressure-triggered with 5 cm H2O pressure support ventilation. MEASUREMENTS AND MAIN RESULTS: Esophageal pressure, airway pressure, and flow signals were monitored. Control data were obtained while the rabbits were breathing room air through the endotracheal tube. With 3-mm inner diameter endotracheal tubes, the negative deflection of esophageal pressure during flow-triggered continuous positive airway pressure was significantly less than control; however, negative deflection of esophageal pressure during pressure triggered continuous positive airway pressure did not significantly differ from control. The application of 5 cm H2O pressure support ventilation with flow triggering decreased negative deflection of esophageal pressure significantly compared with flow-triggered continuous positive airway pressure, pressure triggered continuous positive airway pressure, and control. With endotracheal tube inner diameter of 4 mm, flow-triggered continuous positive airway pressure and pressure-triggered continuous positive airway pressure did not show any differences compared to control. Negative deflection of esophageal pressure differed under all conditions except control when results with the 3-mm inner diameter endotracheal tube were compared with the 4-mm inner diameter endotracheal tube. CONCLUSIONS: Flow-triggering is superior to pressure triggering in the presence of a 3-mm inner diameter endotracheal tube. This difference was not clear with a 4-mm inner diameter endotracheal tube. The size of the endotracheal tube may be the most important variable in evaluating the approach used to ventilate small neonates. PMID- 8205808 TI - Comparison of pH and carbon dioxide tension values of central venous and intraosseous blood during changes in cardiac output. AB - OBJECTIVE: To compare the pH and PCO2 values determined from of simultaneously corrected samples of central venous and intraosseous blood during sequential changes in cardiac output. DESIGN: Prospective, descriptive study. SETTING: An animal laboratory in a university medical center. SUBJECTS: Fourteen mixed breed 4-wk-old piglets. INTERVENTIONS: Animals were anesthetized with ketamine hydrochloride and neuromuscular blockade was induced by the administration of pancuronium bromide. After endotracheal intubation and the institution of mechanical ventilation, a 4-Fr pulmonary artery catheter and a carotid artery cannula were inserted via a cutdown into the right neck of each piglet. A 16 gauge intraosseous needle was inserted into the anteromedial surface of the right tibia. MEASUREMENTS AND MAIN RESULTS: Central venous and intraosseous blood gas samples were obtained simultaneously with thermodilution cardiac output measurements. Cardiac output measurements were as follows: during steady state (0.80 +/- 0.14 L/min), after volume loading of 15 mL/kg (1.00 +/- 0.25 L/min), after three successive bleeds of 15 mL/kg each at 30-min intervals (0.70 +/- 0.28, 0.54 +/- 0.22, and 0.43 +/- 0.16 L/min, respectively) and at exsanguination (unrecordable). Paired t-tests demonstrated no significant differences in pH and PCO2 values between intraosseous and central venous samples under all study conditions. Limits of agreement for difference in PCO2 between sites, within the range of cardiac outputs studied, were -12.86 to 11.38 torr (-1.71 to 1.46 kPa) and for pH were -0.09 to 0.15. CONCLUSIONS: Intraosseous blood samples can be obtained without difficulty even during extreme hypovolemia. The pH and PCO2 values of intraosseous and central venous blood samples were similar under all study conditions. Intraosseous blood may be a useful alternative to central venous blood to assess tissue acid-base status during hemorrhagic shock and other low-flow states. PMID- 8205809 TI - Age-related amrinone pharmacokinetics in a pediatric population. AB - OBJECTIVES: To measure the plasma concentrations of amrinone and N-acetyl amrinone achieved using current pediatric dosing recommendations. To examine the pharmacokinetics of amrinone in an extended age range of pediatric patients. To examine any age-related differences in the relative contribution of hepatic metabolism vs. renal elimination of amrinone. DESIGN: Prospective study. SETTING: A pediatric intensive care unit in a tertiary care teaching hospital. PATIENTS: Thirty-one patients aged 4 days to 15 yrs who required a constant infusion of amrinone. INTERVENTIONS: Blood samples were obtained 15 mins after each 0.75 mg/kg loading dose, and every 6 hrs during a constant infusion of amrinone to measure plasma amrinone, N-acetyl-amrinone and N-glycolyl-amrinone concentrations by high-performance liquid chromatography. Blood samples to measure amrinone, N acetyl-amrinone, and N-glycolyl-amrinone concentrations during elimination were also obtained at regular intervals after discontinuation of the infusion. Six hour urine collections were obtained to measure amrinone renal clearance. MEASUREMENTS AND MAIN RESULTS: Plasma amrinone concentrations > or = 2 micrograms/mL were obtained in 13 of 14 patients after a 3-mg/kg loading dose. There was a six-fold variability in steady-state plasma amrinone concentrations in patients receiving the same ordered infusion rate. There was a significant (p = .001) difference between the ordered and measured amrinone infusion rates. Six (19.4%) of 31 patients had steady-state plasma amrinone concentrations of < or = 2 micrograms/mL. There was a large variability in the volume of distribution, clearance, and elimination half-life which did not appear to be age-related. Renal clearance of amrinone ranged between 0.4 and 2.18 mL/kg/min, and did not increase with age. There was no increase in the proportion of children with a high plasma steady-state N-acetyl-amrinone/amrinone ratio over time from 1 to 24 months of life. CONCLUSIONS: Administering a 3-mg/kg amrinone loading dose in four divided doses over 1 hr resulted in relatively rapid therapeutic plasma concentrations without excessively high concentrations and good clinical tolerance. The wide interindividual variation in clearance and volume of distribution resulted in a variable dose-concentration relationship; children receiving lower amrinone infusion rates may-have subtherapeutic plasma steady state concentrations. There did not appear to be any age-related change in renal clearance or hepatic metabolism of amrinone in children aged 1 to 24 months. PMID- 8205810 TI - Timing and predictors of death in pediatric patients with multiple organ system failure. AB - OBJECTIVES: To describe the timing of onset of organ system failure, multiple organ system failure diagnosis, and the subsequent death in children admitted to a pediatric intensive care unit (ICU). Second, to identify independent risk markers of death in pediatric patients with multiple organ system failure. DESIGN: Review of a database. SETTING: Pediatric ICU within a tertiary care center. PATIENTS: We analyzed the pediatric ICU course of 777 consecutive patients aged < 18 yrs. MEASUREMENTS AND MAIN RESULTS: Eighty-five (10.9%) of 777 children had multiple organ system failure, defined as the simultaneous occurrence of at least two organ system failures. Of 85 children, 37 (43.5%) were postoperative cardiac surgery patients and 48 (56.5%) patients were in the ICU for other reasons. The diagnostic criteria for multiple organ system failure were met on the day of admission by 73 (86%) of 85 patients. The maximum number of organ system failures occurred within 72 hrs in 74 (87%) children. The mortality rate for all patients with multiple organ system failure was 50.6%. Thirty-eight (88.4%) of deaths occurred within 7 days after the diagnosis of multiple organ system failure. Survival analysis was comparable for both postoperative cardiac surgery patients and patients with other diagnoses. Multivariate analysis identified three factors as independent risk markers of death in pediatric patients with multiple organ system failure: maximum number of simultaneous organ system failures during the pediatric ICU stay: odds ratio, 55.9 (95% confidence interval, 7.9 to 396.1); age < or = 12 months: odds ratio, 17.1 (95% confidence interval, 1.8 to 158.7); and the Pediatric Risk of Mortality (PRISM) score on the day of admission: odds ratio, 1.25 (95% confidence interval, 1.1 to 1.5). CONCLUSIONS: The mortality rate associated with multiple organ system failure in pediatric patients is high. The maximum number of simultaneous organ system failures during pediatric ICU stay, age < or = 12 months, and the PRISM score on the day of admission are independent risk markers of death. Diagnosis of multiple organ system failures, development of maximum number of organ system failures, and deaths occur remarkably early after pediatric ICU admission; the rationale for using prophylactic therapy under such circumstances is unclear. PMID- 8205811 TI - Reversible neurologic dysfunction following isoflurane sedation in pediatric intensive care. AB - OBJECTIVE: To examine the relationship between prolonged isoflurane sedation and reversible neurologic dysfunction in children requiring intensive care. DESIGN: Retrospective, case note review from January 1987 to August 1993. SETTING: Pediatric intensive care unit. PATIENTS: Twenty-nine children, aged 6 months to 10 yrs, requiring endotracheal intubation and mechanical ventilation for upper airway infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fourteen patients with laryngotracheobronchitis (croup) and 15 patients with epiglottitis required endotracheal intubation and ventilation. These children were treated with different sedative and muscle relaxant drugs, including opiates, benzodiazepines and chloral hydrate. Twelve (41%) of 29 children were sedated with isoflurane (0.25% to 1.5%) for > 24 hrs. All patients subsequently developed reversible ataxia, agitation, hallucinations, and confusion lasting < or = 72 hrs postextubation. Neurologic dysfunction was not observed in 12 patients who did not receive isoflurane nor in five patients who received isoflurane for between 1 and 15 hrs. Neurologic signs resolved in all patients before hospital discharge, and all children had normal neurologic examinations 4 to 6 wks later as outpatients. CONCLUSIONS: A high occurrence rate of reversible neurologic dysfunction occurs when isoflurane is used as a sedative for > 24 hrs in pediatric patients. PMID- 8205812 TI - Critical care--beyond the ivory tower: the presidential address from the 23rd Educational and Scientific Symposium of the Society of Critical Care Medicine. PMID- 8205813 TI - Critical care research in the 1990s: how our perceptions affect creativity. PMID- 8205814 TI - Impact of a clinical pharmacist in a multidisciplinary intensive care unit. AB - OBJECTIVES: To describe the activities of a clinical intensive care unit (ICU) pharmacist and to determine whether pharmacist-initiated consultations lead to changes in drug costs. DESIGN: Prospective, 3-month study. SETTING: A 15-bed, university-affiliated, tertiary care medical-surgical ICU. INTERVENTIONS: The following ICU pharmacist activities were recorded: providing drug information for physician inquiries; providing drug information for nurse inquiries; clarification of drug orders; drug accessibility information; pharmacokinetic consultation; detection and reporting of adverse drug reactions; and pharmacist initiated therapeutic consultation leading to changes in drug therapy. When changes in drug therapy occurred, drug costs before and after the change were determined. MEASUREMENTS AND MAIN RESULTS: During 54 weekdays, 575 pharmacist interventions occurred (10.7 +/- 5.0 interventions/day). The most common interventions were pharmacist-initiated therapeutic consultations (44.7%, 257/575 of the total), and response to physician requests for drug information (39.0%, 224/575). The most resource-intensive activities were provision of physician drug information and therapeutic consultations (49.6 mins and 35.9 mins per day, respectively). On average, 1.70 hrs (102 mins) per day were spent on all interventions. Therapeutic consultations decreased (47.1%), did not change (42.0%), or increased (10.9%) drug costs for a net savings of $10,010.60 (Canadian) over 3 months, or a projected annual savings of $67,664.24, if clinical pharmacy services were extended to 7 days/wk. CONCLUSIONS: Dedicated ICU pharmacists are crucial healthcare team members in a multidisciplinary ICU. In addition to substantially reducing drug costs, they provide continuity in individualized pharmacotherapeutic care, and serve an important educational function. PMID- 8205815 TI - Practical guide for drug administration by intravenous infusion in intensive care units. PMID- 8205816 TI - Arterial-mixed venous carbon dioxide tension difference in hemorrhage and resuscitation. PMID- 8205817 TI - Outcome after intensive care. PMID- 8205818 TI - Prognostic significance of evoked potentials in acute basilar occlusion. PMID- 8205820 TI - Multiple organ system failure in children. PMID- 8205819 TI - Manipulation of stress gene expression: a novel therapy for the treatment of sepsis? PMID- 8205821 TI - Sedation for mechanically ventilated patients: back to basics please! PMID- 8205822 TI - The critical care pharmacist: what you get is more than what you see. PMID- 8205823 TI - Drug prescribing issues in the intensive care unit: finding answers to common questions. PMID- 8205824 TI - Induction of the heat shock response reduces mortality rate and organ damage in a sepsis-induced acute lung injury model. AB - OBJECTIVE: To test the hypothesis that induction of heat shock proteins before the onset of sepsis could prevent or reduce organ injury and death in a rat model of intra-abdominal sepsis and sepsis-induced acute lung injury produced by cecal ligation and perforation. DESIGN: Prospective, blind, randomized, controlled trial. SETTING: University research laboratory. SUBJECTS: One-hundred forty-two adult Sprague-Dawley rats (weight range 200 to 300 g). INTERVENTIONS: Production of intra-abdominal sepsis and exposure to heat stress. Animals were randomly divided into four groups: heated and septic, heated and sham-septic, unheated and septic, and unheated and sham-septic. MEASUREMENTS AND MAIN RESULTS: We evaluated the mortality rate and pathologic changes in lung, heart, and liver at 18 hrs after cecal perforation, at 24 hrs after removal of the cecum, and at 7 days after perforation. Heated animals exhibited a maximum increase in heat shock protein of 72 kilodalton molecular weight protein concentrations in the lungs and heart 6 to 24 hrs after the hyperthermic stress. By 18 hrs after perforation, 25% of the septic, unheated animals had died whereas none of the septic heated animals had died (p < .005). Septic, heated animals showed a marked decrease in 7 day mortality rate (21%) compared with septic unheated animals (69%) (p < .01). Furthermore, septic heated animals showed less histologic evidence of lung and liver damage than septic unheated animals. CONCLUSIONS: These data suggest that thermal pretreatment, associated with the synthesis of heat shock proteins, reduces organ damage and enhances animal survival in experimental sepsis-induced acute lung injury. Although the mechanisms by which heat shock proteins exert a protective effect are not well understood, these data raise interesting questions regarding the importance of fever in the protection of the whole organism during bacterial infection. PMID- 8205825 TI - Delivery and monitoring of inhaled nitric oxide in patients with pulmonary hypertension. AB - OBJECTIVE: The development of a safe, portable, accurate, and adaptable system to deliver nitric oxide to patients with pulmonary hypertension. DESIGN: A prospective, clinical study. SETTING: Tertiary care pediatric intensive care unit and cardiac catheterization laboratory. PATIENTS: One hundred twenty-three patients (median age 11 months, range 1 day to 72 yrs) with pulmonary hypertension who were administered nitric oxide between November 1991 and July 1993. Ninety-one patients were mechanically ventilated (volume-controlled ventilator, n = 53; pressure-controlled ventilator, n = 5; and a pressure limited, time-cycled infant ventilator, n = 25). The system was adapted to allow high-frequency oscillator (n = 2) or hand ventilation, and for intraoperative use with an anesthesia machine (n = 6). Thirty-two patients were breathing spontaneously through a mask without assistance. INTERVENTIONS: Nitric oxide was delivered at 10 to 80 parts per million (ppm); the dose was adjusted independently of the FIO2 without altering minute ventilation or tidal volume. MEASUREMENTS AND MAIN RESULTS: Nitrogen dioxide was continuously monitored and exceeded 3 ppm in only four patients. Methemoglobin concentrations were < 5% in all but four patients. Nitric oxide doses remained stable, independent of minute ventilation and could be changed easily and quickly. CONCLUSIONS: Inhaled nitric oxide can be administered precisely and reliably through a variety of delivery systems which can be used in patients of any size. Potential toxicity requires careful monitoring and continued improvement on apparatus design. PMID- 8205827 TI - Plasma endotoxin and cytokine concentrations in patients with hemorrhagic shock. AB - OBJECTIVES: The roles of cytokines and endotoxin in hemorrhagic shock, particularly the translocation of endotoxin and bacteria during hemorrhagic shock, were investigated. DESIGN: Prospective study. SETTING: Critical care and emergency center of a university hospital. PATIENTS: Twenty-nine patients with hemorrhagic shock and 20 healthy controls. INTERVENTIONS: Serial blood samples were collected from both study and control patients. Standard resuscitation techniques were used. MEASUREMENTS AND MAIN RESULTS: Plasma levels of endotoxin and various cytokines were determined repeatedly during hemorrhagic shock. Endotoxin was measured using an endotoxin-specific assay in addition to a new perchloric acid method for pretreatment of plasma. Cytokines were measured by commercial enzyme-linked immunosorbent assays. Plasma endotoxin concentrations remained within the normal range for 7 days after admission. Although levels of tumor necrosis factor-alpha and several interleukins increased slightly in some patients, these cytokines did not reach the levels seen in septic shock. CONCLUSIONS: Translocation of bacteria or endotoxin from the gastrointestinal tract into the bloodstream has been noted in animal experiments; however, translocation was not detected in our patients with hemorrhagic shock. PMID- 8205826 TI - Continuous enteral feeding counteracts preventive measures for gastric colonization in intensive care unit patients. AB - OBJECTIVE: To test the influence of continuously administered enteral feeding on gastric pH and gastric colonization in patients receiving or not receiving topical antimicrobial prophylaxis of the oropharynx and stomach, including sucralfate as stress ulcer prophylaxis. DESIGN: Prospective, open trial. SETTING: Two university hospital general intensive care units (ICUs). PATIENTS: Patients (n = 95) with an ICU stay for at least 5 days. INTERVENTIONS: Thirty-one patients received antimicrobial agents into the stomach and oropharynx in combination with sucralfate (1 g/6 hrs) as stress ulcer prophylaxis. Sixty-four other patients did not receive antimicrobial prophylaxis or sucralfate, but instead received gastric pH-increasing stress ulcer prophylactic agents, if indicated. Gastric colonization and gastric pH were measured on admission and subsequently at least two times a week. Forty-eight patients (14 receiving and 34 not receiving antimicrobial prophylaxis) received enteral feeding. MEASUREMENTS AND MAIN RESULTS: Both enteral feeding and gastric pH-increasing stress ulcer prophylaxis independently increased gastric pH: the risks for a gastric pH of > 3.5 were, respectively, 4.54 and 2.04 (odds ratios). Enteral feeding also increased the risk for gastric colonization by potentially pathogenic microorganisms (odds ratio = 4.52). Patients receiving both topical antimicrobial prophylaxis and sucralfate remained free of gastric colonization for a longer period than those patients receiving gastric pH-increasing stress ulcer prophylaxis. In these two groups, patients without enteral feeding remained free of gastric colonization for a longer period than those patients receiving enteral feeding. CONCLUSIONS: Topical antimicrobial prophylaxis, including sucralfate, successfully prevented gastric colonization with potentially pathogenic microorganisms and was correlated with lower gastric pH values. However, the efficacy was markedly decreased when continuous enteral feeding was administered simultaneously. PMID- 8205828 TI - Cardiopulmonary actions of intravenously administered enalaprilat in trauma patients. AB - OBJECTIVE: To determine the cardiopulmonary actions of the intravenous administration of the angiotensin-converting enzyme inhibitor enalaprilat in hypertensive trauma patients. DESIGN: Prospective, before/after trial. SETTING: Intensive care unit (ICU) of a university hospital. PATIENTS: Twenty critically injured and hypertensive ICU patients. All patients were receiving continuous sedation (fentanyl and midazolam) for at least 2 days before the injection of enalaprilat and had a mean arterial pressure (MAP) of > 95 mm Hg. "Responders" were defined as having a decrease in MAP of > 15% within 30 mins after enalaprilat injection. INTERVENTIONS: Intravenous administration of 0.06 mg/kg of the angiotensin-converting enzyme inhibitor enalaprilat. Repeated doses were given when no sufficient response (decrease of MAP of > 15% within 30 mins after injection) was seen ("nonresponders"). MEASUREMENTS: In addition to standard hemodynamic monitoring, right ventricular hemodynamics and oximetric variables were also documented. Measurements were carried out before enalaprilat injection (during hemodynamic steady state [baseline values]) and at 1, 5, 10, 20, 30, 60, and 120 mins after enalaprilat administration. MAIN RESULTS: MAP was successfully controlled in 17 of 20 patients (maximum decrease -27 mm Hg [-26%]). In the three other patients, even reinjection of enalaprilat (0.06 mg/kg) did not sufficiently reduce MAP. In the 17 responders, heart rate did not increase, whereas central venous pressure, pulmonary arterial pressure, and pulmonary artery occlusion pressure decreased significantly after intravenous administration of enalaprilat. Cardiac index changed only slightly (mean maximum +0.70 L/min/m2 [+18%]). Right ventricular ejection fraction increased from 36% to 45% (p < .05); right ventricular end-diastolic and end-systolic volume index decreased significantly. Both systemic and pulmonary vascular resistance indices decreased within the investigation period (-31% and -16%, respectively). Pao2/FIO2, intrapulmonary right-to-left shunting, and oxygen extraction ratio were not altered. Oxygen delivery index (+17%) and oxygen consumption index (+20%) increased during the investigation period (p < .04). CONCLUSIONS: The intravenous administration of enalaprilat successfully decreased blood pressure in most of our patients. Mechanisms other than the renin-angiotensin system also appear to be involved in hypertensive, critically ill patients. Pulmonary function was not altered; right ventricular function, and both oxygen consumption and oxygen delivery improved in the enalaprilat responder group. Thus, the availability of intravenous enalaprilat seems to enlarge our armamentarium for treating hypertension in the critically ill patient. PMID- 8205829 TI - Enalaprilat in acute intractable heart failure after myocardial infarction: a prospective, consecutive sample, before-after trial. AB - OBJECTIVE: To evaluate the acute effects of intravenous enalaprilat infusion in critically ill patients with intractable heart failure after acute myocardial infarction. DESIGN: Prospective, consecutive sample, before-after trial. SETTING: Medical intensive care unit in a university hospital. PATIENTS: Eight consecutive patients with intractable acute heart failure after acute myocardial infarction. All study patients continued receiving inotropic, vasodilating, and diuretic medication at a constant rate. Six patients received steady intermittent mandatory ventilation and two patients were on a continuous positive airway pressure mask during the investigation, all with constant positive end-expiratory pressure. Heart failure was defined as intractable if the pulmonary artery occlusion pressure remained > 20 mm Hg despite this conventional therapy. INTERVENTIONS: Enalaprilat was infused at a rate of 1 mg/hr until the pulmonary artery occlusion pressure decreased by > or = 20%. MEASUREMENTS AND MAIN RESULTS: Central hemodynamics, oxygenation, and hormonal regulation (plasma renin activity, plasma norepinephrine, epinephrine, endothelin, atrial natriuretic peptide, and vasopressin concentrations, serum angiotensin-converting enzyme activity, and serum concentrations of aldosterone) were assessed at baseline before enalaprilat infusion, and repeatedly during 2 hrs after the infusion. The statistical analysis was performed with analysis of variance for repeated measurements. Enalaprilat infusion (median dose 0.3 mg and infusion time 21 mins) caused significant but short-lasting decreases in pulmonary artery occlusion pressure (p = .007), mean arterial pressure (p = .003), mean pulmonary arterial pressure, and rate pressure product. These findings coincided with inhibition of serum angiotensin-converting enzyme activity, an increase in plasma renin activity, and a decrease in plasma endothelin concentrations (p = .041). Enalaprilat had no significant effects on the other hormones studied. Cardiac output and stroke volume index, venous admixture, oxygen extraction ratio, and mixed venous and arterial oxygen saturations remained unchanged. CONCLUSIONS: Adding enalaprilat to conventional therapy makes it possible to transiently relieve pulmonary congestion while maintaining cardiac function and systemic oxygenation. The decrease in plasma endothelin concentrations may have further clinical implications, because endothelin is known to have potent vasoconstricting effects on the coronary circulation and it may also contribute to the extension of myocardial infarction. Whether these observed benefits can be maintained with repeated bolus injections or with continuous infusion of enalaprilat, remains to be settled. PMID- 8205830 TI - Patterns of prescribing and administering drugs for agitation and pain in patients in a surgical intensive care unit. AB - OBJECTIVES: To describe the variety of medications prescribed along with the doses administered and routes of administration, and to delineate the clarity of orders written and the accuracy of transcription of drugs used for sedation, anxiety, pain, and neuromuscular blockade in a surgical intensive care unit (ICU). DESIGN: A prospective, observational study of drug-related information collected from forms used by physicians and nurses. SETTING: Three adult surgical ICUs at an academic medical center. Patients were admitted to a surgical service and co-managed by the surgical ICU team and primary surgical service. PATIENTS: Consecutive patients admitted to all of these units from September 1992 to January 1993. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Information on prescribing and administering sedatives, analgesics, and neuromuscular blocking drugs was obtained from data collected on 221 patients. A total of 202 (91%) patients received, on average, 1.9 +/- 1.4 study drugs (range 0 to 9) in a wide variety of combinations. There were 2,103 total doses administered from 448 drug orders. Ninety percent of study drug orders were written for administration on an "as-needed" basis; in 42% of these orders, the indication for use was not specified. On average, only 27% of the maximal allowable daily dose was administered; this number ranged from 15% for hydromorphone to 77% for chlordiazepoxide. Morphine sulfate, the most commonly prescribed drug, was ordered primarily for intravenous administration in 84% of patients. Morphine sulfate was prescribed using 19 different doses (written as a range of doses) and 13 different dosing intervals. Transcription discrepancies were observed in 17% of orders. In 2.7% of doses, the actual dose that was administered could not be determined. CONCLUSIONS: A wide variety of sedatives and analgesics are frequently used in surgical ICU patients. These agents are often ordered on an "as-needed" basis using a range of doses, sometimes without adequate directions about the indication for their use. Daily doses received are significantly less than their maximum allowable daily doses. Orders for these medications are sometimes transcribed and charted incorrectly. In contrast, neuromuscular blocking agents are not commonly prescribed. Future studies are needed to improve order writing of these agents, and to determine the criteria used by physicians and nurses in the selection and administration of these agents, the outcomes of therapy, and the most cost-effective regimen. PMID- 8205831 TI - Crying wolf: false alarms in a pediatric intensive care unit. AB - OBJECTIVE: To determine the predictive value of patient monitoring alarms as a warning system in a pediatric intensive care unit (ICU). DESIGN: Prospective, observational study. SETTING: Pediatric ICU of a university affiliated children's hospital. INTERVENTIONS: During a 7-day period, ICU staff were asked to record the type and number of alarm soundings. Alarms were recorded as false, significant (resulted in change in therapy), or induced (by staff manipulations; not significant). MEASUREMENTS AND MAIN RESULTS: Sixty-six percent of nursing shifts (928 patient hours of care) responded. There were 2,176 alarms soundings: 1,481 (68%) false, 119 (5.5%) significant, and 576 (26.5%) induced. Alarm origins were: 44% pulse oximeter, 1% end-tidal PCO2, 31% ventilator, and 24% electrocardiograph (EKG). The positive predictive value of alarms were: 7% pulse oximeter, 16% end-tidal PCO2, 3% ventilator, and 5% EKG. The negative predictive value of all alarms were > 97%. More alarms sounded during the 7:00 am to 3:00 pm shift than during the 3:00 pm to 11:00 pm or 11:00 pm to 7:00 am shifts (167 +/- 19 vs. 64 +/- 39 vs. 75 +/- 43, p < .05, respectively). When corrected for number of patients/shift, the occurrence of soundings differed only between day and night (11.4 +/- 1.5/patient/shift vs. 6.1 +/- 1.0, p < .05). CONCLUSIONS: Over 94% of alarm soundings in a pediatric ICU may not be clinically important. Present monitoring systems are poor predictors of untoward events. PMID- 8205832 TI - Derivation of pulmonary capillary pressure from arterial occlusion in intact conditions. AB - OBJECTIVE: To investigate the reliability of the pulmonary capillary pressure measurement with the arterial occlusion technique. DESIGN: Prospective, randomized, controlled study on anesthetized animals. SETTING: A cardiopulmonary research laboratory. SUBJECTS: Seven healthy, mongrel dogs. INTERVENTIONS: The animals were anesthetized, and left thoracotomy was performed. A 7-Fr pulmonary artery flotation catheter was inserted to monitor the pulmonary arterial pressure. Arterial flow to the left lower lobe was monitored with a cuff-type flow probe. A laser Doppler flow probe was placed on the surface of the left lower lobe to monitor flow in the microcirculation. MEASUREMENTS AND MAIN RESULTS: Arterial occlusions were performed by inflating the flotation balloon located in the left pulmonary artery. A monoexponential curve was fitted to a stretch of data between 0.2 to 2 secs post-occlusion and extrapolated back toward time zero. Time zero was defined as the instant when a change in the arterial pressure was first observed. When the balloon was inflated, pulmonary arterial flow and pressure decreased simultaneously; flow reached zero after 72 +/- 5 msecs, while pressure decreased rapidly and thereafter continued to decline more slowly. A change of flow in the main artery was followed by a change in microvascular flow with an 80 +/- 20 msec lag. Thus, if flow in the large arteries was at a peak or a nadir, a peak or a nadir flow in the microcirculation would occur 80 msecs later. Therefore, as a first approximation, we estimated that flow in the arterioles stopped 80 msecs after it had reached zero in the main artery. At this instant of time when flow in the arterioles stopped, the pressure across the arterial tree would have equilibrated. We calculated the arterial occlusion pressure at time zero (when pressure or flow began to change), at the time when pressure and flow had fully equilibrated across the arterial tree, and two other selected instants in between. The extrapolated pressure at these four instants were all < 1.1 mm Hg apart. CONCLUSIONS: Back extrapolation of the postarterial occlusion data to 80 msecs after flow in the main artery reached zero, provided a physiologically correct estimate of capillary pressure. This approach would be equivalent to extrapolating to 152 msecs after the initial change in pressure was noted. Thus, precapillary pressure can be accurately estimated by identifying time zero as described above, fitting the data between 0.2 to approximately 2.0 secs to a -single exponential, and calculating the pressure on the curve at 152 msecs. However, under clinical conditions, only time zero is identifiable from the pressure tracings. Our results show that back extrapolation to any point between zero and 152 msecs is acceptable. The breakpoint on the arterial pressure tracing (if discernible) is perhaps most practical because it falls between zero and 152 msecs. In humans, wave transmission time generally would be in the same range, and thus, the same criteria may be applied. PMID- 8205833 TI - Epinephrine infusion in sheep: systemic and renal hemodynamic effects. AB - OBJECTIVE: To evaluate the dose-response effects of graded epinephrine infusions on systemic and renal hemodynamics. DESIGN: Prospective, dose-response study. SETTING: Laboratory at a university hospital. SUBJECTS: Thirteen conscious, chronically catheterized, adult merino sheep. INTERVENTIONS: Ten sheep received five infusions of epinephrine (5, 10, 20, and 40 micrograms/min; the 40 micrograms/min dose was repeated) and a placebo (saline) on separate days (at least 1 day apart). Each drug infusion was administered for 4 hrs on separate days after a 90-min baseline was established. Plasma catecholamine values and renin activity were measured in an additional three sheep infused with 40 micrograms/min epinephrine. MEASUREMENTS AND MAIN RESULTS: Renal blood flow was measured, using an electromagnetic flow transducer; these data, along with aortic and pulmonary arterial pressure, were continuously recorded after analog-to digital conversion. Cardiac output was intermittently measured by thermodilution. Epinephrine resulted in a dose-dependent increase in mean arterial pressure (p < .001), and in cardiac output at 30, 60, and 120 mins after the start of the infusion. Concurrently, systemic vascular resistance was initially depressed below baseline, but then gradually increased during the 4-hr infusion period. Although a dose-dependent increase in renal vascular resistance was found, 5- and 10-micrograms/min of epinephrine failed to alter renal vascular resistance. However, 20- and 40-micrograms/min of epinephrine increased renal vascular resistance by 77% and 94% respectively, at 10 mins, but these values decreased to 17% and 16% of baseline by 120 mins. Consequently, an early dose-dependent decrease in renal blood flow was also time dependent, with renal blood flow increasing back to or above baseline at all studied infusion rates of epinephrine. CONCLUSIONS: Using a clinically relevant dose regimen, epinephrine increased mean arterial pressure and cardiac output. Renal blood flow decreased transiently, but returned to baseline within 30 to 60 mins. PMID- 8205834 TI - Management of patients after myocardial infarction and thrombolytic therapy. AB - On the basis of the available data concerning the indications for and the timing of arteriography after thrombolysis, the inevitable conclusion is that conservative instead of aggressive management is indicated for the 40% to 50% of patients at low risk who do not have spontaneous myocardial ischemia or myocardial ischemia that was provoked. Factors to be considered in treatment decisions for individual patients after thrombolytic therapy include risk factors before and after thrombolytic therapy, the results of studies assessing conservative versus aggressive post-thrombolytic management, the accuracy of risk stratification by noninvasive testing, and the relevance of the "open artery" hypothesis. The low-risk patient with a left ventricular ejection fraction above 40% and no ischemia during adequate stress testing has a low 3-year mortality rate. Although benefits of routine coronary arteriography exist relative to determining the severity of coronary artery disease and whether the infarct related artery is patent, selective coronary arteriography is a more feasible and less expensive approach for appropriate patients. The low annual mortality rate with this approach is equal to that obtained when patients undergo routine coronary arteriography with myocardial revascularization based upon the result of the routine procedure. The modification of various coronary risk factors appears as valuable for patients who have undergone thrombolytic therapy as for those who did not. Specifically, the cessation of smoking, the control of hypertension, and the treatment of hypercholesterolemia are indicated for patients after thrombolysis when any of these modifiable risk factors are present. Secondary prevention with pharmacologic agents appears to be similar for those who have undergone standard or thrombolytic therapy. Long-term aspirin therapy is routine for secondary prevention; long-term beta-blocker therapy is useful for high-risk patients; and long-term treatment with angiotensin-converting enzyme inhibitors is indicated for patients after thrombolysis who have a low left ventricular ejection fraction. PMID- 8205835 TI - Human pathogenic papillomavirus types: an update. PMID- 8205836 TI - Immortalization and transformation of human cells by human papillomavirus. PMID- 8205837 TI - Protein phosphatase 2A and the regulation of human papillomavirus gene activity. PMID- 8205838 TI - Primer-directed sequencing of human papillomavirus types. PMID- 8205840 TI - Epidermodysplasia verruciformis: immunological and clinical aspects. PMID- 8205839 TI - Molecular pathogenesis of cancer of the cervix and its causation by specific human papillomavirus types. PMID- 8205841 TI - Papillomaviruses and cancer of the upper digestive and respiratory tracts. PMID- 8205842 TI - In vitro systems for the study and propagation of human papillomaviruses. PMID- 8205843 TI - Immune response to human papillomaviruses and the prospects for human papillomavirus-specific immunisation. PMID- 8205844 TI - Vaccination against papillomavirus in cattle. PMID- 8205845 TI - Evolution of papillomaviruses. PMID- 8205846 TI - Epidemiology of cervical human papillomavirus infections. PMID- 8205847 TI - Functions of human papillomavirus proteins. PMID- 8205848 TI - What is a primary care physician? PMID- 8205849 TI - Primum non nocere. Is the therapy worse than the disease? PMID- 8205850 TI - Pulmonary rehabilitation of early COPD. COPD as a systemic disease. PMID- 8205851 TI - Unattended studies of sleep-disordered breathing. PMID- 8205852 TI - Coagulation abnormalities in cancer patients. Clinical relevance. PMID- 8205853 TI - Glucocorticoid-induced bone loss: a neglected problem. PMID- 8205854 TI - Amiodarone and the development of ARDS after lung surgery. AB - An evaluation of amiodarone as prophylactic treatment for supraventricular tachyarrhythmias after pulmonary surgery was stopped because of a high incidence of the adult respiratory distress syndrome (ARDS) after a pneumonectomy. Retrospective analysis of all cases of resection for pulmonary neoplasm in our hospital between 1987 and 1991 indicates that amiodarone may be implicated in the development of ARDS after lung surgery. PMID- 8205855 TI - Pulmonary function before surgery for pectus excavatum and at long-term follow up. AB - Pulmonary function tests were performed before surgery on 152 patients who were operated on for pectus excavatum between 1970 and 1987 and at long-term follow-up to assess the degree of impairment and to investigate any changes caused by surgical correction. The mean age at surgery was 15.3 +/- 5.5 years. Pulmonary function was found to be restricted preoperatively. Multivariate analysis showed that preoperative pulmonary function was not related to age, the severity of the deformity at physical examination, or to pulmonary complaints. Only the patients with obstructive disease showed significantly more pulmonary complaints (p = 0.042). The total lung capacity (TLC) and inspiratory vital capacity (IVC) were significantly related to the age-corrected (delta) anteroposterior diameter of the chest (lower vertebral index [LVI]) (p = 0.0001). At follow-up (mean, 8.1 +/- 3.6 years), the restriction of pulmonary function was increased despite improvement in the symptoms of most patients and despite a significant increase in the anteroposterior diameter of the chest (p = 0.0001): the TLC was decreased from 83.7 percent predicted (pred) preoperatively to 73.8 percent pred (p = 0.0001) and the IVC from 78.3 percent pred to 70.7 percent pred (p = 0.0001). The surgical results were satisfactory in 83.6 percent. No relation was found between the changes in pulmonary function measured at follow-up and the surgical results. Only the age at surgery and the changes in the TLC and IVC at follow-up were significantly related (p = 0.0036, 0.0043, respectively), although the correlation coefficients were low (r = 27 percent and 28 percent, respectively). The reduction in lung function at follow-up was most pronounced in the patients who had the least functional impairment (TLC > 75 percent pred) preoperatively. No correlation was found between the changes in the pulmonary function test results at follow-up and follow-up interval, preoperative delta LVI, and the change in delta LVI at follow-up. PMID- 8205856 TI - External fixation of subglottic tracheal stents. AB - Bronchoscopically placed silicone stents are used increasingly for treating patients with tracheal stenosis due to benign or malignant airway disease. When stenosis occurs in the immediate subglottic region, however, complications of stent insertion, especially migration, are troublesome. The purpose of this report is to describe a technique of external fixation of subglottic stents that may be used when tracheotomy, Montgomery T-tubes, or other therapeutic measures are undesirable or have failed. This technique may also be considered in carefully selected patients with severe malacia and subglottic stenosis who have failed indwelling stent placement because of stent migration. PMID- 8205857 TI - Interbronchoscopist variability in the diagnosis of lung cancer by flexible bronchoscopy. AB - STUDY OBJECTIVE: We evaluated the interbronchoscopist variability in the diagnosis of lung cancer by flexible bronchoscopy. DESIGN AND SETTING: A retrospective review of the bronchoscopic records and clinical charts of patients at a university-affiliated hospital. PATIENTS AND MEASUREMENTS: All records of flexible bronchoscopic procedures performed for the diagnosis of lung cancer were retrospectively reviewed, and procedures that obtained histologic or cytologic evidence of malignancy were considered positive. Rates of positivity were compared according to the following factors: operator, operator experience, bronchoscopic findings, tumor location, and tumor laterality. Factors that affected the positivity rate were evaluated using logistic regression analysis. RESULTS: Of 384 bronchoscopic procedures performed in 353 patients, 275 (72 percent) were positive. The positivity rate differed significantly depending on the operator (p = 0.003) and the bronchoscopic findings (p < 0.001). A difference between operators was noted in technically difficult cases without epithelial or subepithelial findings and when tumors were located in the upper lobe or the superior segment of the lower lobe. The bronchoscopic findings and the operator also emerged as factors significantly affecting the positivity rate in the logistic analysis. CONCLUSIONS: The diagnostic yield of bronchoscopy for lung cancer is dependent on both the type of bronchial lesion present and the bronchoscopist. PMID- 8205858 TI - Use of fiberoptic bronchoscopy in the diagnosis of bronchogenic carcinoma. A study in patients with idiopathic pleural effusions. AB - We reviewed our experience with 115 patients with pleural effusion in whom bronchogenic carcinoma was suspected who underwent fiberoptic bronchoscopy (FOB) to identify those for whom the procedure was useful. In 6 of 12 patients with hemoptysis, 8 of 12 with a mass or infiltrate, and 8 of 18 with atelectasis with negative fluid cytology and 3 of 7 with cytology positive, FOB was useful in diagnosis. Sixty-six patients had an isolated cytology-negative effusion. Seven of 18 with massive effusion had FOB detecting cancer. Fiberoptic bronchoscopy usually was nondiagnostic in lesser-sized effusions (47 of 48). Using outcome for those with nondiagnostic FOB, we established operating characteristics for the procedure. We conclude that FOB is useful in diagnosing bronchogenic carcinoma in such patients when there is hemoptysis, accompanying lung mass or infiltrate, atelectasis, the effusion is massive, or in cytology-positive effusions without obvious primary tumor. Due to the low prevalence of bronchogenic carcinoma in patients with effusions of lesser size, we suggest that in this group FOB not be routinely performed. PMID- 8205859 TI - Peripheral blood lymphocyte subsets and survival in small-cell lung cancer. AB - Measurement of lymphocyte subsets in peripheral blood is likely to reflect immune response of patients and therefore may be linked to survival in small-cell lung cancer (SCLC). Forty patients with SCLC (14 with limited and 26 with extensive disease at study entry) were included and followed for up to 23 months. Peripheral blood lymphocytes were determined by flow cytometry and levels for total-, T-, B-, helper-, suppressor-, activated T-cells and natural killer cells established and the T-helper-suppressor ratio (H-S ratio) calculated. Quartiles of lymphocyte subset cell counts at the start of follow-up and for the change over follow-up were investigated. Cox regression models indicated that H-S ratio was a significant predictor (p = 0.02) of survival. The risk ratio, after adjustment for competing risk factors, sex, age and stage of disease, was found to be 0.66 (95 percent confidence intervals, 0.46 to 0.95) and predicted that for each quartile of greater H-S ratio, the risk of death decreased by 34 percent. For change in cell counts over follow-up, total lymphocytes (p = 0.02) demonstrated a significant association with survival. Although our observation is limited by the fact that 13 patients were unavailable for follow-up, we conclude that H-S ratio can serve as an easily accessible marker of immune function and possible prognostic value in SCLC. PMID- 8205860 TI - Application of electrical impedance analysis for diagnosis of a pulmonary mass. AB - The electrical impedance of a pulmonary mass was measured in 53 patients of whom 44 had primary lung cancer, 5 had metastatic lung tumor, and 4 had organizing pneumonia. Because biologic tissue can be regarded, electrically, to consist of extracellular resistance (Re), intracellular resistance (Ri), and the electrical capacitance of the cell membrane (Cm), these three parameters were calculated from the measured electrical impedance of tissue by a curve-fitting technique using a computer program. The Re of lung tissue was significantly greater (p < 0.01) and the Cm of lung tissue was significantly less (p < 0.01) than that of a pulmonary mass. The Re of malignant tumors (both lung cancer and metastatic tumors) was significantly greater (p < 0.01) and the Cm of malignant tumors was significantly less (p < 0.01) than that of organizing pneumonia. With this information, we used a biopsy needle to diagnose nine intrathoracic lesions. This technique additionally allowed us to confirm the proximity of the needle tip of the mass. The electrical impedance of the lung mass was measured through the biopsy needle using a modified impedance analysis system before the biopsy was performed. There were no false-negative results, and one false-positive result. The rapid measurement of the electrical impedance of a pulmonary mass, preoperatively, may be of value in the clinical evaluation of a pulmonary mass both by facilitating needle guidance and by permitting diagnosis based on electrical impedance. PMID- 8205861 TI - Association of thrombosis-inducing activity (TIA) with fatal hypercoagulable complications in patients with lung cancer. AB - We previously reported that thrombosis-inducing activity (TIA) is present in plasma from patients with advanced lung cancer. Of 73 patients with non-small cell lung cancer, stages IIIb and IV, 41 (56 percent) had such activity in plasma. The median survival time was significantly shorter in the TIA-positive vs the TIA-negative group. When 34 of those 73 patients who had died at Kyushu University Hospital were evaluated for the incidence of disseminated intravascular coagulation (DIC) and adult respiratory distress syndrome (ARDS), they were significantly higher in the TIA positive group (p < 0.05). The DIC occurred in 7 of 20 patients positive for TIA and 5 died of ARDS. In contrast, in the 14 TIA-negative subjects, only 1 patients experienced DIC and none died of ARDS. Peripheral platelet counts, which had been rather elevated on the day of hospital admission, were below normal within 1 week of death in 40 percent of the 20 patients who were positive for TIA. These observations suggest that TIA may be responsible at least in part for the increased activity of the coagulation system and the high incidence of DIC and ARDS in patients with advanced lung cancer. PMID- 8205862 TI - Dynamics of oxygen uptake for submaximal exercise and recovery in patients with chronic heart failure. AB - STUDY DESIGN AND OBJECTIVES: Attainment of a steady state for oxygen uptake (VO2) during constant work rate exercise has been reported to take longer for patients with chronic heart failure (CHF) compared with normal. The steady state is also delayed in normal subjects during high-intensity exercise compared with moderate exercise, however, and the delay correlates with the degree of associated lactic acidosis. To determine whether prolonged kinetics of VO2 are attributable solely to the reduction of exercise capacity in CHF, VO2 kinetics were compared for patients with CHF and normal subjects, both for exercise of matched absolute work rate and for matched relative work intensity. SUBJECTS: Eighteen men with CHF and 10 normal men. METHODS AND RESULTS: Subjects performed 6 min of constant work rate cycle ergometry with breath-by-breath measurement of VO2. Patients were studied using 25 W, and a work rate midway between the lactic acidosis threshold and maximal capacity (50 percent delta). Normal subjects were tested similarly, and also at a work rate matched to the patients' average 50 percent delta work rate. The VO2 kinetics were characterized by the mean response time (MRT) to attain the 6 min VO2 value. Rates of recovery of VO2 were analyzed for 2 min following exercise. For the same absolute work rate, VO2 MRTs were significantly longer for patients than controls (25 W, 67 +/- 26 vs 37 +/- 25 s; approximately 60 W, 87 +/- 20 vs 54 +/- 27 s), but there was no significant difference in VO2 MRT between the two groups at a matched intensity of 50 percent delta (87 +/- 20 vs 81 +/- 18 s). However, the decrease in VO2 during 2 min of recovery was slower for the patients on all comparisons, even for matched exercise intensity. CONCLUSION: The VO2 dynamics for submaximal exercise are slowed in CHF. The slower dynamics are not entirely accounted for by the relatively higher intensity of a given work rate, since delayed recovery is evident even at a matched relative work intensity. Exercise intolerance in CHF is characterized not only by decreased maximal exercise capacity, but also by slower adaptations to and from submaximal levels of exercise. PMID- 8205863 TI - Effects of aerosol ipratropium bromide on cardiac vagal tone. AB - Thirty-one adult asthmatic subjects, aged 18 to 40 years, were administered both ipratropium bromide and placebo, in two sessions, held at least 2 days apart, in balanced order. Pulmonary function, heart period (milliseconds between heart beats), and respiratory sinus arrhythmia (a measure of cardiac vagal tone) were assessed before drug administration and 45 min thereafter. Ipratropium bromide had no significant effect on cardiac vagal tone, while it did produce improvement in pulmonary function. PMID- 8205864 TI - Risk of pneumothorax not increased by obstructive lung disease in percutaneous needle biopsy. AB - All computed tomography directed lung biopsies from 1987 to 1991 were retrospectively reviewed. Pneumothorax occurred in 33 of 93 (35 percent) patients; 16 of these patients or 17 percent overall required a chest tube. No correlation was found between the presence of obstructive lung disease and the incidence of pneumothorax. Patients with smaller lesions were more likely to incur a pneumothorax. No relation was found with central or peripheral location, patient's age, or the operator and the incidence of pneumothorax. Patients with a pneumothorax were more likely to require a chest tube if they had obstructive lung disease. PMID- 8205865 TI - Pulmonary function among cotton textile workers. A study of variability in symptom reporting, across-shift drop in FEV1, and longitudinal change. AB - Longitudinal variability in respiratory responses, including symptom reporting and across-shift change in ventilatory function, were examined in relation to long-term loss of ventilatory function in a group of 447 cotton textile workers in Shanghai, China. The study used a standardized respiratory questionnaire and standardized spirometric testing before and after a work shift on the first day of the workweek. Prediction equations for FEV1 were generated from a group of silk textile workers from the same city. Environmental samples included both vertical elutriated cotton dust and endotoxin levels. There was considerable variability in symptom reporting between the baseline and 5-year follow-up survey for all symptoms. However, subjects who consistently reported symptoms had a significantly accelerated 5-year loss in FEV1 compared with those who never reported symptoms. Subjects with symptoms of chest tightness or dyspnea at one survey lost FEV1 at a rate intermediate between the never or both groups. Moreover, subjects with an across-shift change in FEV1 of more than 5 percent at both surveys had the greatest loss in FEV1 over 5 years (-267 ml) when compared with one-time responders (-224 ml), and nonresponders (-180 ml), though the differences were not significant. Workers with chest tightness and chronic bronchitis in both surveys were overrepresented in the high dust and endotoxin areas. Our results indicate that even with substantial survey-to-survey variability in responses, there is important information contained in both questionnaires and across-shift spirometry. Among cotton workers, consistent responders to either symptom questionnaire or across-shift FEV1 decrements of > or = 5 percent appear to be at increased risk for lung function impairment. PMID- 8205866 TI - Decreased bone mineral density in premenopausal asthma patients receiving long term inhaled steroids. AB - Inhaled corticosteroids have become a key element in the maintenance treatment of bronchial asthma. It is well-known that long-term systemic steroid use causes osteoporosis, whereas its inhaled counterpart has been believed to be devoid of such a side-effect. However, recent studies showed that administration of inhaled corticosteroids was associated with biochemical evidence of derangement in bone turnover. We therefore studied bone mineral density (BMD) by dual energy x-ray absorptiometry in 30 patients (18 females, 12 males) with bronchial asthma treated with steroids, essentially by the inhaled route only (both nasal and tracheobronchial), and compared them with healthy subjects individually matched for age, sex, menopausal status, and body mass index (BMI). There was a significant decrease in BMD in the patient group at the hip (neck of femur, p = 0.007; trochanter of femur, p = 0.034; Ward's triangle, p = 0.016) and the lumbar area of the spine (L2-4, p = 0.041). Further analysis showed that this difference from control subjects was mainly seen in the female patients and not in the male patients (neck of femur, p = 0.049; Ward's triangle, p = 0.025; lumbar spine, p = 0.039). In the female patients, there was significant negative correlation of BMD of the lumbar area of the spine and the trochanter of femur with daily inhaled steroid dose and positive correlation of BMD of the trochanter with BMI. PMID- 8205867 TI - Effect of whole-body exposure to cold and wind on lung function in asthmatic patients. AB - To assess the effect of subfreezing temperature and wind on lung function in asthmatic patients, an exposure to subfreezing temperature at rest, a moderate exercise challenge at subfreezing temperature, and a similar exercise challenge at room temperature were performed in 19 stable asthmatic subjects in an environmental chamber with an artificial wind. The mean maximal falls in FEV1 were 5.3, 11.7, and 4.8 percent, respectively. The two challenges at subfreezing temperature caused statistically significant changes in FEV1, but the exercise challenge at room temperature had no effect. A large variation in the sensitivity to cold was found. The time courses of the responses varied between the challenges, suggesting at least partially different mechanisms. The results indicate that even moderate exercise can cause severe bronchoconstriction in certain stable asthmatic subjects at climatic conditions similar to the Scandinavian winter. The importance of reflex mechanisms causing bronchoconstriction in physiologic conditions is discussed. PMID- 8205868 TI - Comparative safety and efficacy of single or twice daily administration of inhaled beclomethasone in moderate asthma. AB - OBJECTIVES: In the treatment of stable mild to moderate asthma, twice-daily administration of inhaled steroids may allow adequate control of the asthma; however, comparisons of the efficacy of once- or twice-daily administration brought contradictory results. This study is a randomized, double-blind crossover trial, set to determine if inhaled beclomethasone dipropionate given once daily in the late afternoon or at bedtime can be as effective as a twice-daily regimen in the treatment of moderate asthma. DESIGN: Subjects were randomly assigned to 3 different dosing regimens of inhaled beclomethasone: (1) regimen A, a twice-daily dose of 500 micrograms in the morning and at bedtime; (2) regimen B, a single dose of 1,000 micrograms in the late afternoon; and (3) regimen C, a single dose of 1,000 micrograms at bedtime. PATIENTS AND PARTICIPANTS: Enrolled in the study were 42 subjects who required 500 micrograms of inhaled beclomethasone dipropionate twice daily to control symptoms of asthma and to minimize use of beta 2-adrenergic agonists, according to criteria suggested in a recent international consensus on asthma therapy. Prior to receiving therapy with inhaled steroids, all of these patients either had chronic symptoms of asthma that required administration of a short-acting beta 2-agonist at least twice per day, or had nocturnal asthma symptoms at least once per week. THERAPY: After a 2 week baseline evaluation, each subject was given the 3 treatment regimens in randomized order, each for a period of 4 weeks. Subjects were asked to record daily symptoms of asthma and peak expiratory flows in the morning and evening. At the end of each treatment period, spirometric data and airway responsiveness to methacholine were measured. MEASUREMENTS AND RESULTS: Thirty-seven subjects completed the study. No significant difference was found among the 3 treatment regimens for asthma symptoms, FEV1, the provocative concentration of methacholine causing a 20 percent decrease in the FEV1 (PC20) (geometric means, 1.41, 1.09, and 1.09 mg/ml), and mean morning and evening peak expiratory flow rates (PEFR). The plasma cortisol level and the adrenocorticotropic hormone (ACTH) response were not significantly different among treatments, nor were side effects, which were minimal. CONCLUSION: In moderate asthma controlled with a twice-daily dose of inhaled beclomethasone, a single total daily dose administered in the late afternoon or in the evening provides as good control of asthma for 2 months. PMID- 8205869 TI - Dose-effect relationship of the beta-agonists fenoterol and salbutamol in patients with asthma. AB - QUESTION: What is the relative per microgram potency and side effect profile of the beta-agonists salbutamol and fenoterol? METHOD: The relative bronchodilator (delta FEV1, V25, V50) potency and side effect profile (delta tremor, heart rate, breathlessness, BP) of nebulized salbutamol and fenoterol were evaluated by means of a randomized, double-blind, crossover, cumulative (50 to 2,500 micrograms) dose-response study. Both beta-agonists were administered to 12 patients with stable asthma over age 18 years with baseline FEV1 between 35 to 70 percent predicted. RESULTS: (1) Salbutamol and fenoterol both provided significant bronchodilatation compared with baseline. (2) There was no dose-effect difference between the two beta-agonists with respect to bronchodilator response. (3) Overall there was no significant difference between the side effect profiles of the two beta-agonists, although at the highest dose of fenoterol, there was marginally greater tremor when measured by accelerometry. (4) There was no difference in the vital signs or subjective patient evaluations of tremor, palpitations, or breathlessness as estimated by a visual analogue scale. (5) No significant adverse reactions occurred. SUMMARY AND CONCLUSION: Equivalent bronchodilatation and similar side effect profiles were measured in a group of patients with stable asthma after treatment with nebulized salbutamol or fenoterol in the dose range 50 to 1,250 micrograms (cumulative, 2,500 micrograms). This indicates that both beta-agonists have similar per microgram potency and side effect profiles. Observed clinical differences in response or side effects associated with fenoterol metered-dose inhaler administration may be a result of its higher dose per puff metered-dose inhaler formulation. PMID- 8205870 TI - Clinical efficacy of doxycycline for pleurodesis. AB - To determine the efficacy of doxycycline as a pleural sclerosing agent, we examined the outcomes in 31 patients (aged 31 to 87 years) receiving doxycycline (500 to 1,000 mg) through a chest tube for malignant pleural effusions or persistent bronchopleural fistulae. Of the 27 patients with malignant pleural effusions, 21 patients had a complete short-term response (no fluid reaccumulation during the initial hospitalization); 5 of the 6 short-term nonresponders had partial control of effusions, with improvement in respiratory symptoms. Of the 23 patients who survived longer than 1 month, 15 patients did not have reaccumulation of fluid during follow-up. All four patients with persistent bronchopleural fistulae had resolution of their air leaks; one patient had recurrence with a partial pneumothorax. Pleural pain controllable with narcotic therapy was the only important complication. Thus, doxycycline is a suitable substitute for tetracycline as a pleural sclerosing agent. PMID- 8205871 TI - Relationship between pleural effusion and pericardial involvement after myocardial revascularization. AB - The explanation for the high incidence of pleural effusion after cardiac surgery is unclear. There is a high incidence of left pleural effusion with inflammatory pericardial disease. We hypothesized that after coronary artery bypass grafting (CABG) there would be a higher incidence of pleural effusions in patients with pericardial involvement. We prospectively studied 47 patients undergoing elective CABG; 17 had only saphenous vein grafts (SVG group) and 30 received at least one internal mammary artery graft (IMA group) in addition to SVG. Patients had a chest radiograph, chest ultrasound, and an echocardiogram on the 7th, 14th, and 30th postoperative days. Seven days after the surgery, 42 to 47 patients (89.4 percent) had a pleural effusion and 36 (76.6 76.6 percent) pericardial involvement. No relationship was found between the presence of a pleural effusion and a pericardial effusion (p > 0.05). On the 14th postoperative day, 36 patients (76.6 percent) had a pleural effusion while 33 patients (70.2 percent) had a pericardial effusion. There was a significant relationship between the presence of a pleural effusion and a pericardial effusion (p < 0.05). On the 30th postoperative day, 27 patients (57.4 percent) had a pleural effusion and 25 (53.2 percent) had a pericardial effusion. Again, there was a significant relationship between a pleural effusion and a pericardial effusion (p < 0.05). Finally, there was no relationship between the ejection fraction and the presence of pleural effusion at any time (p > 0.05). From this study, we conclude that there is a high prevalence of both pleural and pericardial effusion postoperatively in patients undergoing CABG. Both types of effusions tend to be asymptomatic, gradually disappear, and are more common in the IMA group. Patients who have a persistent pericardial effusion are more likely to have a persistent pleural effusion. PMID- 8205872 TI - Factors related to sleep apnea syndrome in sleep clinic patients. AB - We examined 129 patients recruited from two sleep clinics to study the sleep apnea syndrome (SAS), defined by the apnea-hypopnea index (AHI) > or = 10. Information was registered from a self-administered questionnaire, basal physical measurements, and polysomnography. In 68 subjects recorded for two consecutive nights, a high correlation was found between first- and second-night AHIs (r = 0.89). Habitual loud snoring and breathing arrests during sleep were associated with AHI > or = 10. A model including these two variables, sex, age, and body mass index was created in order to predict AHI > or = 10 and with which it was possible to successfully classify almost three of four patients. Among subjective sleep questionnaire items, only daytime sleepiness was related to drops of transcutaneous oxygen tension. These discrepancies in the observed relationship between sleep parameters and subjective sleep items reduce the questionnaire value in epidemiologic settings where it aimed to detect SAS, as defined solely by the AHI value. PMID- 8205873 TI - Snoring and nocturnal oxygen desaturations in an Italian middle-aged male population. Epidemiologic study with an ambulatory device. AB - Recent studies have suggested that portable monitoring may be a valid means of finding respiratory disturbances in epidemiologic research on a large scale. The aim of this cross-sectional study was to evaluate by means of an appropriately validated portable instrument (MESAM 4) the nocturnal oxygen desaturations in a representative sample of adult male population in North Italy. We randomly chose 750 subjects: 399 subjects (53.2 percent) agreed to participate and a complete evaluation of nocturnal recording was possible in 349 subjects (87.5 percent). Seventeen percent of subjects were every-night snorers; a number of oxygen desaturations per hour (ODI) > 10 was found in 13.7 percent, and an ODI > 20 resulted in 4.8 percent. Age, neck circumference corrected for height, snoring time (measured by MESAM), and self-reported snoring were the variables best explaining ODI in our multivariate approach. This study reports the highest prevalence, using nocturnal oxygen desaturation indices as marker, of sleep disordered breathing than any reported until now in a general population. PMID- 8205874 TI - Aerosol characteristics of 99mTc-pentetic acid (DTPA) and synthetic surfactant (Exosurf). AB - This study evaluated the feasibility of using 99mTc-pentetic acid (DTPA) as a radioactive tracer for aerosolized synthetic surfactant (DPPC, cetyl alcohol, tyloxapol). The 99mTc-DTPA was admixed with surfactant and aerosolized using a nebulizer system interfaced to a ventilator with a cascade impactor attached to the endotracheal tube. Particle size distribution for DPPC, cetyl alcohol, and 99mTc-DTPA were almost identical during the 0- to 15-, 15- to 30-, and 0- to 30 min collection periods. Tyloxapol exhibited a unique distribution pattern with increased deposition in large (> 10 microns) and small (0.65 to 1.1 microns) particles. The mass median aerodynamic diameter for all aerosolized components was in the respirable range of 2.1 to 2.5 microns. A mixture of 99mTc-DTPA with synthetic surfactant appears to be a reasonable method to evaluate surfactant deposition. PMID- 8205875 TI - Controlled utilization of induced sputum analysis in the diagnosis of Pneumocystis carinii pneumonia. AB - We investigated the outcome and potential cost savings of a system designed to limit physician access to induced sputum analysis (ISA) for the diagnosis of Pneumocystis carinii pneumonia (PCP). Four respiratory medicine physicians screened all requests for ISA to determine the pretest likelihood of PCP. Twenty two of 102 requests for ISA over a 1-year period were denied due to a low clinical suspicion for PCP. Seven individuals had a definitive alternative diagnosis confirmed and the remaining 15 were empirically treated for a presumptive diagnosis. All individuals were followed for at least 60 days or until death. None of the 22 individuals developed PCP during the follow-up period. We estimate that this approach saved $27,474, avoided exposure of health care workers to Mycobacterium tuberculosis, and was educational for the referring physicians. PMID- 8205876 TI - Recovery of viruses other than cytomegalovirus from bronchoalveolar lavage fluid. AB - STUDY DESIGN: To determine the yield and diagnostic significance of performing viral cultures on specimens obtained by bronchoalveolar lavage (BAL) in immunocompromised patients. DESIGN: Review of all BAL specimens submitted for viral culture over a six-year period. SETTING: Referral laboratory within a university hospital. The majority of specimens came from the university hospital, and for those cases, review of the patient's underlying disease, clinical presentation, and outcome was performed. PATIENTS: Over 95 percent of the patients had recognized underlying immunosuppression. INTERVENTION: None. MEASUREMENTS AND RESULTS: Cultures were done on 1,199 BAL specimens for viruses, and in 90 (8 percent), non-cytomegalovirus (CMV) viruses were recovered. These included herpes virus (53), influenza (11), parainfluenza (7), rhinovirus (12), adenovirus (5), enterovirus (1), and respiratory syncytial virus (1). Complete medical records were available for 1,020 (85 percent) of the BAL specimens, and the 77 patients with non-CMV viral pneumonia were studied in more detail. In 31 (40 percent) patients, virus was the only potential pathogen recovered. CONCLUSION: The recovery of respiratory viruses followed epidemic trends in the community and was often associated with self-limited illnesses without an increased mortality. The isolation of herpesvirus in patients without AIDS was associated with increased mortality in comparison with patients with AIDS (p < 0.01). This study demonstrates that viruses other than CMV may be recovered from BAL of patients with lower respiratory disease and may be the only pathogen recovered. PMID- 8205877 TI - Preoperative respiratory muscle training. Assessment in thoracic surgery patients with special reference to postoperative pulmonary complications. AB - STUDY OBJECTIVE: To assess the usefulness of preoperative respiratory muscle training to increase muscle strength and its effects on postoperative pulmonary complications. DESIGN: We measured maximum inspiratory (MIP) and maximum expiratory (MEP) mouth pressure before and after training in 50 patients undergoing thoracic surgery. For control purposes, MIP and MEP were measured in 50 age- and sex-matched healthy subjects at two different times without training. RESULTS: Preoperative respiratory muscle training increased both MIP and MEP significantly (p < 0.01), while the control subjects showed no increase in these parameters. Eight patients who had postoperative pulmonary complications had significantly lower values (p < 0.01) and did not show significant increases in either MIP or MEP even after the training, unlike the other patients, who were without postoperative pulmonary complications. On the other hand, there were also another six patients who had equally low MIP and MEPs before training, but who raised their values with training and avoided the postoperative pulmonary complications. CONCLUSION: Preoperative respiratory muscle training may prevent postoperative pulmonary complications by increasing both inspiratory and expiratory muscle strength in patients undergoing thoracic surgery. Patients with respiratory muscle weakness have a higher risk of postoperative pulmonary complications. PMID- 8205878 TI - Comparison of intrapulmonary percussive ventilation and chest physiotherapy. A pilot study in patients with cystic fibrosis. AB - STUDY OBJECTIVE: To compare the intrapulmonary percussive ventilator (IPV) to chest physiotherapy (P&PD) with respect to acute changes in (1) pulmonary function and (2) sputum physical properties in patients with cystic fibrosis (CF). DESIGN: Randomized crossover. SETTING: Community-based CF referral center. PARTICIPANTS: Nine nonhospitalized person (range, 7 to 40 years; median, 12.4 years) with moderate to excellent Shwachman scores. INTERVENTIONS: Three treatment regimens: (1) 2.5 mg albuterol delivered via IPV (internal percussive component activated); (2) 2.5 mg. albuterol delivered via IPV (internal percussive component inactivated), followed by P&PD; and (3) 2.5 mg albuterol delivered via updraft nebulizer, followed by P&PD. MEASUREMENTS AND RESULTS: Outcome measures included pulmonary function testing (PFTs) and quantitative and qualitative sputum analysis. Among the three treatment groups, there were no significant differences in the change in predicted PFTs 1 h or 4 h after treatment, nor in the volume of sputum expectorated in the first 4 or in the subsequent 20 h. Among patients receiving IPV, more serious disease was associated with greater improvement in FEF25-75 1 h after treatment, but these differences disappeared by 4 h. There were no meaningful differences in viscoelastic characteristics of sputum expectorated after each treatments. Participants reported general satisfaction with no adverse effects while using IPV. CONCLUSIONS: This initial pilot study suggests (1) stable patients with CF tolerated one treatment of IPV without adverse sequelae, and (2) IPV was as effective as standard aerosol and P&PD in improving short-term PFT results and enhancing sputum expectoration. PMID- 8205879 TI - Head position and oral vs nasal route as factors determining endotracheal tube resistance. AB - STUDY OBJECTIVE: We performed this in vitro study to determine the following: (1) if there is any significant difference in resistance between comparably sized endotracheal tubes (ETTs) in simulated anatomic oral and nasal conformations: (2) if neck flexion would increase the resistance of the ETT; and (3) if a wire reinforced tube in simulated oral conformation would minimize the resistance increase at bends in the tube. DESIGN: The pressure drops (the change in pressure the flow through the ETT) at the proximal end of three sizes of tubes (6-, 7-, and 8-mm inner diameter) were measured in anatomic conformations at flows ranging from 20 to 100 L/min with the tubes warmed to 37 degrees C. RESULTS: There were no significant differences in pressure drops between comparably sized ETTs in the nasal vs oral conformation at any flow tested. Maximal head flexion produced a small increase in pressure drop for the standard 6-mm ETT but not for the larger tubes. The wire-reinforced tubes, when compared with the standard 7- and 8-mm ETTS, actually had greater pressure drops across the tubes at high flows. CONCLUSIONS: (1) Pressure differences between ETTs in nasal and oral conformations with comparable size and length are insignificant, even at high flow rates. (2) Maximal neck flexion does not deform the tube enough to make a clinically significant difference in resistance in vitro, although the 6-mm ETT had a slightly higher resistance in flexion. (3) A size 7- or 8-mm reinforced ETT has a higher resistance compared with a standard ETT. PMID- 8205880 TI - Hemodynamic and oxygen transport characteristics of common ventilatory modes. AB - We studied hemodynamic and oxygen transport parameters in 12 stable critically ill patients on assist control (ACV), synchronized intermittent mandatory (SIMV), and pressure support (PSV) ventilatory modes. Patients were optimally ventilated on ACV, were awake, and capable of spontaneous breathing. After baseline measurements on ACV, patients were placed on SIMV and PSV for 30 min each and measurements were repeated at the end of each period. The SIMV rate (f) was 75 percent of the rate on ACV. The PSV was set at a level enough to maintain a tidal volume (VT) equal to that on ACV. The FIo2 was kept constant on all three modes. Patients on SIMV and PSV maintained similar minute ventilation as when on ACV but with significantly lower peak and mean inspiratory pressures than on ACV. However, f increased and VT decreased significantly on SIMV. Hemodynamic and oxygen transport parameters were not significantly different among the three groups, although there was a tendency toward higher cardiac index, oxygen transport, and oxygen consumption on SIMV and PSV. We conclude that in stable critically ill patients, SIMV and PSV used according to our study protocol for 30 min can provide adequate ventilation with lower airway pressure and possibly less adverse effects on hemodynamic and tissue oxygenation parameters compared with ACV. Because of a significant decrease in VT and an increase in f seen with SIMV, PSV may be a more desirable mode for ventilatory support. PMID- 8205881 TI - Unplanned extubations. AB - STUDY OBJECTIVE: A prospective study of all unplanned adult extubations was conducted for 4 months period in four intensive care units (ICUs) of a community hospital. Our objective was to document the incidence of unplanned extubations, discern possible variables predictive of occurrence and outcome, and formulate preventive measures and guidelines for reintubation. DESIGN: Prospective case series. SETTING: Hospital with 525 beds and four ICUs: medical-surgical-trauma, neurology-neurosurgery, cardiovascular, and coronary care. PATIENTS: All adult patients intubated in four ICUs for a 4-month period. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Of 460 adults intubated in the 4-month period, 13 (3 percent) unplanned extubations occurred. Six patients were reintubated because of apnea, tachypnea, hypoxia, or other factors. Seven were not reintubated. Variables examined included the ventilator settings before to self-extubation, duration of intubation, arterial blood gases after self-extubation, Glasgow Coma Scale and Acute Physiology and Chronic Health Enquiry (APACHE) scores, time and location (ICU), nasal or oral method of intubation, and the mechanism of self extubation. CONCLUSIONS: Our data suggested that self-extubation is relatively rare in our institution and that about half of self-extubated patients were reintubated. Staff vigilance, a proper weaning period, and the nasal method of intubation were some of the factors to which we attributed this low occurrence rate. However, a larger patient study population is required to show conclusively effective preventive measures and establish guidelines for reintubation. PMID- 8205882 TI - Effect of positive pressure ventilation on impedance plethysmography. AB - It has been stated that positive pressure ventilation (PPV) may cause false positive impedance plethysmography (IPG) results because PPV can decrease venous outflow. We studied 36 patients who were being weaned from mechanical ventilation to determine the effect of PPV on IPG. Patients had IPGs performed during spontaneous ventilation and while receiving mechanical ventilation in the assist/control (A/C) mode without positive end expiratory pressure (PEEP) and with 10 cm H2O PEEP. No patient developed a positive IPG with institution of PPV (mean airway pressure = 6.8 cm H2O), or with PEEP (mean airway pressure = 14.9 cm H2O). The IPG values for venous capacitance and venous outflow did not change during either mode of mechanical ventilation. There also was no tendency for positive pressure ventilation to move IPG results in the direction of a positive test. In summary, PPV does not cause IPG results to be false positive, nor does it move IPG results toward the discriminant line that separates normal from abnormal results. PMID- 8205883 TI - Legionnaires' disease. PMID- 8205884 TI - Left lung atelectasis in a smoker. PMID- 8205885 TI - Estimation of triggering work of breathing. The dependence on lung mechanics and bias flow during pressure support ventilation. AB - Work of breathing necessary to trigger a ventilator (WOBtr) was calculated during pressure support ventilation (PSV), and the effect of bias flow on WOBtr was evaluated. A spring-loaded bellows type lung model with two bellows placed in series was used to simulate spontaneous breathing. A Venturi mechanism of jet flow generated subatmospheric pressure inside the diaphragm bellows simulated inspiratory effort. The lung compliance (CL) was set at 0.3 L/cm H2O or 0.05 L/cm H2O. The airway resistance (Raw) was set at 5, 20, or 50 cm H2O/L/s. Pressure support levels were increased from 0 to 45 cm H2O. Sensitivity was set at 2 cm H2O. No bias flow was used at first. The WOBtr was calculated using a pressure volume (P-V) loop derived from the diaphragm bellows movement during the triggering period. We determined WOBtr and its dependence on the various pressure support (PS) levels, CL and Raw. To evaluate the effects of bias flow on WOBtr and triggering delay, a ventilator was put in the PSV mode, with various bias flow rates (from 0 to 20 L/min) at a sensitivity of 2 cm H2O. We found that when no bias flow was used, WOBtr increased with an increase in both Raw and end expiratory lung bellows pressure which was considered as auto-PEEP. With bias flow, both triggering delay and WOBtr increased. An increase in bias flow at a given PS level resulted in both decreased pressure support time and tidal volume (VT). It is concluded that the bias flow system is not desirable for use during PSV. PMID- 8205886 TI - Inhaled nitric oxide reverses hypoxic pulmonary vasoconstriction in dogs. A practical nitric oxide delivery and monitoring system. AB - Nitric oxide (NO) is a potent dilator of vascular smooth muscle that likely represents an important endothelium-dependent relaxing factor. Recent interest has focused on inhaled NO as a pulmonary vasodilator. The purpose of this study was to design a reliable NO delivery system with on-line monitoring of NO and nitrogen dioxide (NO2) concentrations, and to test the effects of inhaled NO in a dog model of acute hypoxic pulmonary vasoconstriction (HPV). Six canines were studied. Marked HPV was induced using a hypoxic gas mixture. Using a standard blender. NO was delivered through a volume-cycled ventilator. We were able to rapidly adjust the delivered NO concentration using this system. An on-line chemoluminescence analyzer was used to continuously measure NO and NO2 concentrations. Inhaled NO at 40 and 80 ppm for 30 min rapidly reversed HPV in all animals (PVR 502 +/- 154 dynes.s.cm-5 with hypoxia, 244 +/- 52 with 40 ppm NO, 227 +/- 47 with 80 ppm NO). No significant NO2 or methemoglobin production was noted during the study. We conclude that inhaled NO can be easily delivered through a ventilator and the dose rapidly adjusted, NO and NO2 concentrations can be monitored continuously on-line, inhaled NO rapidly reverses HPV in dogs, and with short-term NO inhalation, there is no significant NO2 or methemoglobin formation. Inhaled NO may, therefore, have a future clinical role as a new agent in the diagnosis and treatment of other forms of pulmonary hypertension. PMID- 8205887 TI - Persistence of respiratory syncytial virus genome and protein after acute bronchiolitis in guinea pigs. AB - Children with acute respiratory syncytial virus (RSV) bronchiolitis often develop sequelae of recurrent wheezing and asthma. To determine whether RSV persists within the lung after resolution of acute bronchiolitis, we examined the lungs of guinea pigs 60 days after intranasal inoculation with either human RSV (n = 10) or uninfected cell culture supernatant (n = 11). Evidence of viral persistence within the lung was determined by viral culture to test for replicating virus, immunohistochemistry to test for viral protein, and the reverse transcriptase polymerase chain reaction (RT-PCR) to test for viral genomic RNA. Lungs were also examined histologically for evidence of bronchiolar inflammation or increased numbers of mast cells in the airway walls. All viral cultures were negative; however, there was positive immunohistochemical staining of occasional alveolar macrophages in six of ten RSV-inoculated guinea pigs while RT-PCR was positive in seven of ten RSV-inoculated animals. The six guinea pigs with evidence of RSV by immunohistochemistry and RT-PCR showed excess bronchiolar polymorphonuclear cell infiltrates (p < 0.005) but no increase in the number of airway wall mast cells. These results show that RSV protein and genomic RNA can persist in the lungs of experimentally inoculated guinea pigs for at least 60 days after infection and that persistence of the virus within alveolar macrophages might contribute to the pathogenesis of chronic bronchiolar inflammation. PMID- 8205888 TI - Recurrent asthma despite corticosteroid therapy in a 35-year-old woman. PMID- 8205889 TI - Starting an academic career. A survey of junior academic pulmonary physicians. AB - OBJECTIVE: To learn about the status of junior faculty in the specialty of pulmonary diseases and about their attitudes concerning their future in academic medicine. DESIGN: Mailed survey. PARTICIPANTS: A total of 209 junior pulmonary faculty were reported by the directors of the 106 US pulmonary training institutions with at least 3 fellow training positions; 157 (75 percent) responded to our questionnaire. RESULTS: Most respondents described themselves as happy and productive, and almost all planned to stay in academic medicine. However, some problems were evident that could interfere with their plans to remain: a lack of protected time for research (only 15 percent of assistant professors and instructors spent 75 percent or more of their time in research), a lack of understanding about the rules and procedures of promotion (only 31 percent said they understood), failure of communication with the Chiefs of the Division and of Medicine (less than half had had a meeting about promotion with the Chief of the Division, 16 percent with the Chairman of Medicine), and a concern about their financial security (73 percent were concerned). Although women, who represented only 13 percent of the respondents, reported similar work hours and publication rates, they were less optimistic about promotion than the men (40 percent of women considered their chance for promotion good to excellent vs 64 percent of men). The junior faculty reported that the greatest obstacles to their academic success were insufficient protected time for their research, maintaining research productivity, and inadequate and uncertain funding. CONCLUSIONS: The success of junior faculty is important to the success of academic medicine. More attention should be paid to ensuring protected continuous time for research, educating about promotion, and improving funding opportunities. PMID- 8205890 TI - Left upper lobe mass and diffuse reticular-nodular infiltrate. AB - We encountered a clinical problem in a young man who presented with a left upper lobe mass and a diffuse reticular-nodular infiltrate. We thought we had appropriately applied Murphy's Law (the famed bank robber who "went where the money is"), and Ockham's Razor (the philosopher William of Ockham [1285 to 1349] "Entities are not to be multiplied beyond necessity") as we rapidly diagnosed the lung mass with computed tomography, scintigraphy, and fine-needle aspiration. However, when his invaluable previous chest radiographs arrived, bronchoscopy with transbronchial biopsy, bronchoalveolar lavage, brushings, and postbronchoscopy sputum revealed the more ominous diagnosis in this patient. This case illustrates the complementary nature of current imaging and bronchoscopy techniques; but, even more importantly, it demonstrates the value of the history coupled with the previous radiograph. Even an unusual case can provide lessons in cost containment. PMID- 8205891 TI - Agnogenic myeloid metaplasia with extramedullary hematopoiesis and fibrosis in the lung. Report of two cases. AB - Agnogenic myeloid metaplasia (AMM) is a chronic hematologic disorder with a long clinical course, characteristically accompanied by extramedullary hematopoiesis (EMH) in various organs, most commonly the spleen and liver. We describe two cases of AMM with clinically significant and ultimately fatal EMH and associated fibrosis in the lung and pleura. The literature on AMM and EMH involving the lung and pleura is reviewed. Three similar cases were found. PMID- 8205892 TI - Atrioventricular node re-entry of the common variety. Unusual location for the fast pathway. AB - Radiofrequency ablation was attempted in a 17-year-old man with atrioventricular node re-entry of the common variety. Energy was delivered to three sites around the ostium of the coronary sinus. The third attempt resulted in a sudden increase in AH interval with loss of retrograde conduction. The arrhythmia was no longer inducible. These observations may suggest the unusual location of the fast pathway. PMID- 8205893 TI - Cavernous destruction of an upper lung lobe in a healthy young man. An unusual roentgenographic presentation of allergic bronchopulmonary aspergillosis. AB - We describe a 32-year-old man with no history of pulmonary disease who presented with extensive cavernous destruction of the right upper lobe as an incidental finding on a chest x-ray film. All major criteria of allergic bronchopulmonary aspergillosis (ABPA) were present. Histologic examination of the resected lobe showed the typical features of ABPA. The differential diagnosis of multiple cavitating lesions should include ABPA. PMID- 8205894 TI - Typhoid fever associated with adult respiratory distress syndrome. AB - Adult respiratory distress syndrome (ARDS) is rarely reported in association with typhoid fever despite the fact that sepsis is a common manifestation and endotoxemia has been described in this multisystem condition. We describe the course of a patient with ARDS and typhoid fever. With conventional treatment of the lung injury and with specific antimicrobial therapy, the patient survived. Recent consensus definitions of sepsis and ARDS simplified reporting of this case. Clinicians caring for individuals from or recent visitors to developing countries should be aware of the association of typhoid fever, sepsis, and ARDS. PMID- 8205895 TI - Transcatheter intrapleural urokinase for loculated pleural effusion. AB - Two patients who had undergone coronary artery bypass graft surgery in the mid 1980s and who had repeat coronary artery bypass graft procedures in 1992 developed loculated, bloody pleural effusions. Percutaneous catheter drainage and installation of intrapleural urokinase led to resolution of these loculated effusions without morbidity. This procedure should reduce the length of hospitalization and treatment for patients with loculated pleural effusions. PMID- 8205896 TI - Torsades de pointes arrhythmia in a patient with left ventricular myxoma. AB - A 38-year-old woman suffered from syncopes due to torsades de pointes arrhythmias. Echocardiography showed a left ventricular mass that was resected. By immunohistochemical investigations, an organized thrombus was excluded and the diagnosis of a rare ventricular myxoma was confirmed. Postoperatively the arrhythmias resolved without recurrence. We conclude that left ventricular myxoma may cause life-threatening arrhythmias, possibly by irritation of cardiac mechanoreceptors. To our knowledge, this is the first case of a left ventricular myxoma associated with a torsades de pointes arrhythmia. PMID- 8205897 TI - Treatment of a bronchopleural fistula with a Fogarty catheter and oxidized regenerated cellulose (surgicel). AB - A patient with bronchopleural fistula was successfully treated by occluding the fistula with an inflated Fogarty catheter balloon packed with oxidized regenerated cellulose (Surgicel) using a fiberoptic bronchoscope. After 48 h, the balloon was deflated, the fistula had sealed, and the patient did well. This simple and relatively noninvasive therapy was effective in this patient who was not a surgical candidate. PMID- 8205898 TI - Left internal thoracic artery graft occlusion following mediastinal radiation therapy. AB - Premature coronary artery disease is a late consequence of mediastinal radiation therapy. Many of these patients have been successfully treated with coronary bypass surgery. A 51-year-old man underwent bypass surgery for severe multivessel coronary disease 18 years following radiation therapy for a posterior mediastinal tumor. Recurrent angina 1 year later occurred following closure of the left internal thoracic artery graft. We suspect that this occurred as a consequence of injury sustained during mediastinal irradiation. Patients who have undergone prior mediastinal radiation therapy may not be assured the excellent long-term patency of the internal thoracic artery graft which has been reported for the general population. Saphenous vein grafts probably should be considered instead. PMID- 8205899 TI - Intravascular bronchioloalveolar tumor with skin metastases. AB - Intravascular bronchioloalveolar tumor (IVBAT) is a rare pulmonary tumor that occurs in the younger age groups. In the present article, we describe a patient who manifested systemic growth after the resection of the primary tumor. Skin metastasis, which has never been reported, is histologically examined. PMID- 8205900 TI - Intrathoracic chemothermotherapy following panpleuropneumonectomy for pleural dissemination of invasive thymoma. AB - We report a case of pleural dissemination of invasive thymoma, which was successfully treated with intrathoracic chemothermotherapy following panpleuropneumonectomy. Intrathoracic chemothermotherapy in combination with surgery may be a hopeful adjuvant treatment to control pleural disseminated lesions of invasive thymoma. PMID- 8205901 TI - Aortic valve papillary fibroelastoma. A diagnosis by transthoracic echocardiography. AB - Cardiac papillary fibroelastomas are unusual, frond-like growths typically found on cardiac valves, diagnosed incidentally on autopsy or cardiac surgery, but rarely during life. We report a rare case of an aortic valve papillary fibroelastoma detected by transthoracic echocardiography and confirmed by histologic study. PMID- 8205902 TI - Bronchogenic squamous cell carcinoma complicating localized recurrent respiratory papillomatosis. AB - Bronchogenic squamous cell carcinoma has been reported in patients with recurrent respiratory papillomatosis (RRP) extending into the tracheobronchial tree even in the absence of a history of radiation therapy or smoking. We present a case of bronchogenic squamous cell carcinoma developing in a patient with RRP localized to the larynx for 45 years. PMID- 8205903 TI - Diffuse alveolar hemorrhage associated with Mycoplasma hominis respiratory tract infection in a bone marrow transplant recipient. AB - An 18-year-old woman developed respiratory distress and diffuse pulmonary infiltrates after allogeneic bone marrow transplantation. Bronchoalveolar lavage findings indicated diffuse alveolar hemorrhage. Cultures of the lavage fluid and the pharynx grew Mycoplasma species; the pharyngeal isolate was identified as Mycoplasma hominis. Mycoplasma hominis infection may have an etiologic role in diffuse alveolar hemorrhage. PMID- 8205904 TI - Persistent asthma after inhalation of a mixture of sodium hypochlorite and hydrochloric acid. AB - Chlorine gas inhalation can lead to temporary mucous membrane irritation, pulmonary edema, and transient bronchospasm. Existence of respiratory sequelae is debated. We report a case of asthma, persisting 2 years after the inhalation of a mixture of sodium hypochlorite and hydrochloric acid. Bronchial histologic findings and transmission electron microscopy examinations showed uncommon abnormalities supporting irritation for cause of this nonimmunologic asthma. PMID- 8205905 TI - Surgical repair of esophageal perforation in cirrhotic patients with varices. AB - A 51-year-old woman, a known alcohol abuser, had sclerotherapy for esophageal varices from portal hypertension. A perforation of the distal esophagus, diagnosed several days later, could not be closed primarily at thoracotomy due to extensive bleeding. The method of "exclusion and diversion in continuity" was modified by ligation of the esophagogastric junction with absorbable suture over a tube stent. The perforation healed and patency of the esophageal lumen was demonstrated 2 weeks later. This alternative life-saving procedure may be useful in chronic esophageal perforation, especially in cirrhotic or otherwise debilitated patients. PMID- 8205906 TI - Hereditary angioedema presenting with adult respiratory distress syndrome. AB - Adult respiratory distress syndrome (ARDS) could be related to upper airway obstruction. Mechanical obstruction and complement activation could lead to ARDS development. We describe a patient with hereditary angioedema, laryngeal edema, and ARDS. PMID- 8205907 TI - The pivotal role of transesophageal echocardiography in the management of traumatic thoracic aortic rupture with associated intra-abdominal hemorrhage. AB - Rupture of the thoracic aorta after blunt trauma, particularly when associated with multiple injuries, presents a major problem of resuscitation and management. Transesophageal color Doppler echocardiography (TEE) during laparotomy played a major role in confirming the diagnosis of thoracic aortic rupture in a patient. PMID- 8205908 TI - Validation of new pulsed Doppler echocardiographic techniques. PMID- 8205909 TI - Oral anticoagulants. PMID- 8205910 TI - Temperature in the stability of blood gases. PMID- 8205911 TI - Transcutaneous partial oxygen tension and lung mechanics during methacholine inhaled challenge. PMID- 8205912 TI - Alpha 1-antitrypsin phenotypes and bronchial asthma. PMID- 8205913 TI - Pain control after thoracotomy. PMID- 8205914 TI - Determining the size of pneumothorax. PMID- 8205915 TI - Fiberoptic bronchoscopy and intracranial pressure. PMID- 8205916 TI - The dialogue continues. Thoracoscopy forum. PMID- 8205917 TI - Endobronchial tuberculosis. Report of 102 cases. PMID- 8205918 TI - Migration medicine. The challenge of tuberculosis. PMID- 8205919 TI - Raised pleural adenosine deaminase. Does it mean tuberculosis? PMID- 8205920 TI - Alkaline phosphatase. Distinguishing between pleural exudates and transudates. PMID- 8205921 TI - Chlamydia pneumoniae. PMID- 8205922 TI - Continuous infusion oral lorazepam for patients in the ICU. PMID- 8205923 TI - Critical illness in pregnancy. PMID- 8205924 TI - Obstructive sleep apnea and pharyngeal wall collapsibility. PMID- 8205925 TI - Extralobar pulmonary sequestration. PMID- 8205926 TI - Different vasoactive mechanisms of various pulmonary vasodilators. PMID- 8205927 TI - Tracheal occlusion. PMID- 8205928 TI - Systemic sclerosis, small airways dysfunction, and bronchial hyperreactivity. PMID- 8205929 TI - Value of oral hygiene before expectoration of sputum for routine bacterial culture. PMID- 8205930 TI - Foreign body aspiration with mediastinal migration and superior vena cava penetration. PMID- 8205931 TI - Equip the units with oxygen sensors. PMID- 8205932 TI - Individualization of 5-fluorocytosine therapy. AB - Using a convenient and fast HPLC procedure we determined serum concentrations of the fungistatic agent 5-fluorocytosine (5-FC) in 375 samples from 60 patients treated with this drug. The mean trough concentration (n = 127) was 64.3 mg/l (range: 11.8-208.0 mg/l), the mean peak concentration (n = 122) was 99.9 mg/l (range: 25.6-263.8 mg/l), the mean nonpeak/nontrough concentration (n = 126) was 80.1 mg/l (range: 10.5-268.0 mg/l). Totally 134 (35.7%) samples were outside the therapeutic range (25-100 mg/l), 108 (28.8%) being too high, 26 (6.9%) being too low. Forty-four (73%) patients showed 5-FC serum concentrations outside the therapeutic range at least once during the treatment course. In a prospective study we performed 65 dosage predictions on 30 patients by use of a 3-point method previously developed for aminoglycoside dosage adaptation. The mean absolute prediction error of the dosage adaptation was +0.7 mg/l (range: -26.0 to +28.0 mg/l). The root mean square prediction error was 10.7 mg/l. The mean predicted concentration (65.3 mg/l) agreed very well with the mean measured concentration (64.6 mg/l). The frequency distribution of 5-FC serum concentrations indicates that 5-FC monitoring is important. The applied pharmacokinetic method allows individual adaptations of 5-FC dosage with a clinically acceptable prediction error. PMID- 8205933 TI - Serum levels of flurithromycin ethylsuccinate in healthy volunteers. AB - The serum levels of flurithromycin ethylsuccinate achieved 30 min after a single oral dose of 375 mg were found to be equal or above the minimal inhibitory concentrations for sensitive strains, when administered to 12 healthy volunteers. The serum half-life was found to be approximately 4 h. PMID- 8205934 TI - In vitro antibacterial activity of FK037, a new parenteral broad-spectrum cephalosporin, against recent clinical isolates in the fields of obstetrics and gynecology. AB - The antibacterial activity of a new parenteral cephalosporin, FK037 was assessed against recent aerobic and anaerobic strains isolated from patients in the fields of obstetrics and gynecology during the period between January 1992 and June 1993. The MICs of FK037 for 90% of the clinical isolates tested were 0.10 microgram/ml for Escherichia coli and Klebsiella pneumoniae, 0.20 microgram/ml for Streptococcus agalactiae, 0.39 microgram/ml for Gardnerella vaginalis, 0.78 microgram/ml for Staphylococcus epidermidis, Peptostreptococcus anaerobius and Mobiluncus spp., 1.56 micrograms/ml for Peptostreptococcus magnus, 3.13 micrograms/ml for methicillin-sensitive Staphylococcus aureus, 25 micrograms/ml for methicillin-resistant S. aureus (MRSA), Bacteroides fragilis and Prevotella disiens, 100 micrograms/ml for Bacteroides thetaiotaomicron and Prevotella bivia; and > 100 micrograms/ml for Enterococcus faecalis. FK037 was superior in potency to ceftazidime against all strains except E. faecalis, P. anaerobius and P. bivia. It was 4- to 16-fold more active than cefotaxime against aerobic gram positive bacteria and P. disiens, and its activity was similar to that of cefotaxime against the other strains. FK037 had 4- to 16-fold stronger activity than flomoxef against MRSA, S. agalactiae and E. coli and a similar activity to flomoxef against the other strains except G. vaginalis and B. fragilis that were 4-fold more sensitive to flomoxef than to FK037. PMID- 8205935 TI - In vitro and in vivo antibacterial activities of FK037, a new parenteral cephalosporin. AB - In vitro and in vivo antibacterial activities of FK037, a new parenteral cephalosporin, were compared with those of cefpirome, ceftazidime and flomoxef. The advantages of in vitro activity of FK037 were as follows: (1) a broad spectrum antibacterial activity, (2) the most potent activity (MIC90: 25 micrograms/ml) of the cephalosporins tested against highly methicillin-resistant Staphylococcus aureus (H-MRSA), (3) a strong activity against Enterobacter spp. and Citrobacter freundii resistant to the third-generation cephalosporins tested. The MICs of FK037 for 90% of the clinical isolates tested (MIC90s) were 0.012 microgram/ml for Streptococcus pyogenes, 0.05 microgram/ml for Escherichia coli, 0.1 microgram/ml for Streptococcus pneumoniae, 0.2 microgram/ml for Haemophilus influenzae and Proteus mirabilis, 0.39 microgram/ml for Klebsiella pneumoniae, 1.56 micrograms/ml for methicillin-sensitive S. aureus, Proteus vulgaris and Enterobacter aerogenes, 3.13 micrograms/ml for Staphylococcus epidermidis and Moraxella catarrhalis, 6.25 micrograms/ml for C. freundii, 12.5 micrograms/ml for low-level methicillin-resistant S. aureus (L-MRSA), Enterobacter cloacae and Pseudomonas aeruginosa, and 25 micrograms/ml for H-MRSA and Serratia marcescens. FK037 was similar in potency to cefpirome against strains except MRSA, and was superior to ceftazidime and flomoxef against strains except P. vulgaris and/or M. catarrhalis. The increase in MICs of FK037 against 2 L-MRSA strains (2- or 4 fold) was smaller than that of cefpirome and flomoxef (16- to 64-fold) after the third serial culture in the presence of each drug. FK037 was highly bactericidal against S. aureus, E. coli, K. pneumoniae and P. aeruginosa at the MIC or higher. FK037 had a potent protective activity against murine experimental systemic infections due to a wide variety of bacteria. Its protective activity was the strongest among the cephalosporins tested against H-MRSA and Acinetobacter calcoaceticus. Against the other strains, FK037 was as effective as cefpirome and similar or superior to flomoxef and ceftazidime though it was inferior to ceftazidime against P. aeruginosa. Transmission electron microscopic studies revealed that FK037 inhibited septum formation and induced thick cross walls and bacteriolysis at the division sites in MRSA after 4 h incubation. PMID- 8205936 TI - Comparative activity of beta-lactam antibiotics against 'intrinsically' ticarcillin-resistant strains of Pseudomonas aeruginosa. AB - The in vitro activity of piperacillin, cefoperazone, cefsulodin, ceftazidime, aztreonam and imipenem was studied against 44 isolates of Pseudomonas aeruginosa with 'intrinsic' resistance to ticarcillin in comparison with 20 ticarcillin susceptible strains, by MIC determination and the disk diffusion test. The activity of the antibiotics, imipenem excepted, against the resistant strains was reduced when compared to the susceptible strains. The most significant reduction was found for aztreonam and the least significant for ceftazidime. When considering the breakpoints, all strains were intermediate with aztreonam and cefoperazone, but most of them remained susceptible to ceftazidime, piperacillin and cefsulodin. PMID- 8205937 TI - Enhancement of doxorubicin-induced cytotoxicity by hyperthermia in Ehrlich ascites cells. AB - Hyperthermia (HPT) at 43 degrees C for 30 min increased the cytotoxic activity of doxorubicin against the growth of Ehrlich ascites carcinoma cells. There was more delay in tumor growth with 89% inhibition in the tumor volume and 90% increase in the survival of the tumor-bearing animals compared to control group. Combination of HPT with doxorubicin showed a more pronounced inhibitory effect on tumor content of DNA, RNA, protein, cholesterol, total lipid and acid phosphatase activity. HPT did not significantly affect the doxorubicin uptake into tumor cells, but it has some inhibitory effect on some vital components. Along with other results, our data suggest the benefit of using HPT to enhance the cytotoxic activity of doxorubicin with a consequent reduction of doxorubicin dose and hence a decrease of its serious side effects. PMID- 8205938 TI - Relationships between structure and antiretroviral activity of thiosemicarbazone derivatives. AB - In an attempt to develop anti-AIDS drugs, the compound isatin beta thiosemicarbazone has been subjected to systematic structural modifications. The resulting synthesized thiosemicarbazone derivatives (TSCDs) were examined for their ability to act as antiretrovirus agents in a model system--2M3/M cell system--consisting of B lymphocytes transformed by the v-abl oncogene and chronically infected with a retrovirus, the Moloney leukemia virus (M-MuLV). The efficacy of the synthesized TSCDs against retroviruses was determined by assaying the therapeutic index (TI) values of the compounds. The results enabled the classification of TSCD groups based on the relationship between chemical structure and antiretroviral activity. The compound N-allylisatin-beta':4' diallylthiosemicarbazone showed the highest TI value and efficiently suppressed the chronic infection of M-MuLV in continuous long-term treatment. PMID- 8205939 TI - Magnetic resonance imaging in children receiving quinolones: no evidence of quinolone-induced arthropathy. A multicenter survey. AB - Twenty-nine children with cystic fibrosis (CF) were investigated for quinolone induced arthropathy. Magnetic resonance imaging (MRI) was performed in 14/14 children treated with ofloxacin or ciprofloxacin and in 10/15 of those never treated with quinolones. The frequency of pathologic MRI findings, concerning cartilage thickness, careful analysis of the cartilage structure, presence of edema, cartilage-bone borderline and the presence of fluid in joints did not show any difference between both groups. Thus the presence of quinolone-induced arthrotoxicity cannot be confirmed in this study. PMID- 8205940 TI - [Routine intravenous urography before colorectal resections?]. AB - The value of preoperative intravenous urography (IVU) to prevent iatrogenic damage to the urogenital tract was investigated in a series of 236 females and 188 males (mean age 54 [5-87] years) who underwent an operation on the colon or rectum between April 1988 and March 1992. The operations were: 101 right and 49 left hemicolectomies, 125 sigmoid resections, 74 anterior rectum resections, 58 abdomino-perineal rectum amputations and 17 total colectomies. Preoperative IVU was performed in 279 patients (65.8%), while in 145 (34.2%) urgency of the operation or intolerance to contrast medium prevented the procedure being done. The results were abnormal in 75 of the 279 IVUs (26.9%). Of the latter, only 19 (6.8%) of the abnormalities were related to the colorectal disease (renal obstruction due to tumour: 9, malignant invasion of the bladder: 5, ureter displacement: 5). Other diagnostic procedures had given abnormal results in six patients, although the preoperative IVU had been unremarkable. Iatrogenic damage to a ureter occurred in only one patient: the IVU had been normal. No ureteral damage occurred in any of the patients who had not had an IVU. These data indicate that the decisive factor in preventing intraoperative damage to a ureter is not a preoperative IVU but careful intraoperative dissection and visualization of the ureter. There is, therefore, no need for routine preoperative IVU in these cases. PMID- 8205941 TI - [The effect of blood pressure-reducing therapy with captopril on tubular marker excretion in type-1 diabetics with nephropathy]. AB - A prospective open clinical trial was carried out with 23 hypertensive type I diabetics (13 men, ten women, mean age 49 +/- 9.1 years, duration of diabetes 18 +/- 9.1 years) with early nephropathy. Glomerular and tubular renal function and metabolic parameters were monitored during 8 months' treatment with the angiotensin converting enzyme (ACE) inhibitor, captopril, in addition to previous antihypertensive treatment with one or more drugs. Blood pressure control tended to improve on captopril (systolic pressures 152 +/- 13 vs 140 +/- 13 mm Hg, P < 0.05; diastolic pressures 89 +/- 10 vs 87 +/- 10 mm Hg, not significant). Proteinuria (> 0.5 g/24 hours) fell into the microalbuminuria range (albumin excretion 2-20 mg/mmol creatinine) in four out of 13 patients, and microalbuminuria disappeared in four out of ten patients. Urinary levels of the brush border enzyme N-acetyl-beta-D-glucosaminidase (NAG), a marker of tubular dysfunction, were initially raised and fell significantly after 8 months' treatment with captopril (20.3 +/- 14.4 vs 8.8 +/- 8.1 U/g creatinine; P < 0.01). Captopril did not affect metabolic control (HbA1, total, HDL and LDL cholesterol, triglycerides, apolipoproteins A1 and B) or the insulin dosage. These results show that long-term treatment with captopril may favourably influence both albumin excretion and NAG activity, a marker of tubular dysfunction, in type I diabetics with nephropathy. PMID- 8205942 TI - [Lupus erythematosus in old age]. AB - Over a period of 2 months an 88-year-old man developed progressively more severe breathing-related pain under the right shoulder blade, loss of appetite, general weakness, depressive mood, sub-febrile temperature and nocturnal sweating. Various inflammation parameters were raised (sedimentation rate 43 mm in the first hour; C-reactive protein 26 mg/dl; white cell count 12,500/microliters). There also were pleural effusion and signs of mild nonspecific hepatitis. Antibiotics were administered because bacterial pneumonia was suspected. But the patient's condition deteriorated and he developed nightly periods of disorientation. There was no evidence for any advanced malignancy. Immunological tests pointed towards older-onset systemic lupus erythematosus: titre for antinuclear antibodies markedly raised to 1:20 480; anti-DNA titre moderately raised to 1:125 IU/ml. The patient's general condition and the pleuritic pain improved within 2 days under treatment with prednisone (50 mg daily); the depression, disorientation and fever receded within a week. The anti-DNA titre fell to 47 IU/ml after 8 weeks. He was able to resume his usual social activities and was kept on a maintenance prednisone dose of 5.0 mg daily. PMID- 8205944 TI - [Fenoterol]. PMID- 8205943 TI - [The problems of long-term immunosuppression after organ transplantation]. PMID- 8205945 TI - [Acetylsalicylic acid in arterial circulatory disorders. Which dosage in which indication?]. PMID- 8205946 TI - [The opening of physician mail in the hospital. The judgement of the Higher Labor Court of Niedersachsen of 15 September 1993]. PMID- 8205947 TI - [Paradoxical cerebral embolism during fibrinolytic therapy in deep venous thrombosis of the leg and pulmonary embolism]. PMID- 8205948 TI - [Perinatal infection by hepatitis C viruses]. PMID- 8205949 TI - [Restraint devices for animals--historical and animal welfare aspects]. AB - A historical review is given on the reasons to use restraint measures in animals, their definitions and classifications as well as their mode of action. An attempt is made to give an assessment of these measures according to animal welfare aspects formerly and today. Special emphasis is put on considerations in conformity with the "reasonable reason", as required in the German Animal Welfare Act. PMID- 8205950 TI - [Piglet castration--pain sensation and pain elimination]. AB - Electroencephalographic (EEG) recordings performed in piglets during Trapanal anaesthesia showed distinct changes in bioelectrical brain activity in some piglets when castration was carried out. Only an additional extradural anaesthesia seemed to interrupt the transmission of peripheral pain stimuli to the central nervous system. Based on the protocol used EEG did not reveal a marked response to noxious stimulation. Castration of piglets up to two weeks of age were performed during general anaesthesia with Trapanal or Disoprivan or local anaesthesia with Hostacain or without any anaesthesia. The different modes of anaesthesia have had no effects to postoperative wound healing and weight gain between groups as well as between males and females within single groups. With regard to insufficient analgesia and/or partially extreme secondary effects the application of investigated anaesthetic methods on the occasion of castration of piglets is not justifiable at present. Castration in piglets up to an age of two month without anaesthesia is allowed by the animal protection law. However, due to improved wound healing and decreased response to surgical stimulus we suggest to perform castration during the first 10 days after delivery. PMID- 8205951 TI - [CO2/O2 anesthesia for the castration of male piglets (preliminary results)]. AB - Introduction of anaesthesia with CO2/O2 (60% to 40%) is possible within 90 and 120 seconds. There are moderate to excessive excitations occurring as part of state II of anaesthesia. Anaesthesia (during castration) in CO2/O2-atmosphere produces excellent analgesia and relaxation. The duration of castration surgery is much shorter under CO2-anaesthesia than without anaesthesia. Blood cortisol levels are significantly higher after castration without CO2-anaesthesia. About 5 minutes after CO2/O2-anaesthesia and castration surgery, piglets are already awake and standing. PMID- 8205952 TI - [Animal welfare aspects of broiler husbandry--studies of fattening cockerel husbandry in the administrative district of Weser-Ems]. AB - In January 1993 a working team "animal protection in poultry fattening" at the district council of Weser-Ems presented a report of important aspects of animal welfare in broiler fattening in the district of Weser-Ems. The following main points were discussed: lighting, stable-climate, litter, feed and water, diseases and stocking density. A list of claims for animal welfare in broiler production is given. PMID- 8205953 TI - [Animal welfare law requirements for calf, swine and laying hen husbandry- experiences from Thuringen]. AB - Results of an analysis are presented, concerning the situation of animal welfare in keeping and housing of calves, pigs and laying hens. It is observed, that stockholders are making great efforts to follow the animal welfare regulations. Remaining problems of animal welfare in farms are described. PMID- 8205954 TI - [Possibilities for the all-year free-range raising of horses]. AB - The ethological concept concerning supply of needs an avoidance of damage is mentioned as a possibility for the evaluation of welfare aspects related to animal management. The 250 Dulmen horses kept on 300 ha by the Duke of Croy show what must be provided for horse-keeping in a semi-natural environment: Sufficient food and water, efficient shelter as well as adequate structures for the needs of horses concerning social and comfort behaviour. A catalogue of factors, functions and facilities for this kind of horse-keeping is presented. PMID- 8205955 TI - [Animal welfare and safety aspects for coach driving]. AB - Driving a harnessed horse team requires conformity of horses, driver and vehicle, if one of the three components is in disorder, animal welfare as well as the safety of man and animals are at the - stake. This paper deals with a first testing of a graduated draft power device in order to obtain detached performance readings of the horses. PMID- 8205956 TI - [Ecological barrier effects of highways on mammals living in the wild--an animal welfare problem]. AB - In the course of may 1992 to April 1993, ecological barrier effects to the Hanover-Berlin Autobahn (Germany) on mammalian wildlife were investigated. In this period 1566 carcases of various species were found on the road. Traffic volume showed an increase of 600% from 1989 (15,000 cars/24 hr) to 1992 (90,000 cars/24 hr). Wildlife use of 13 highway underpasses was monitored by video camera and countline checkpoints. Though they had various dimensions nearly all underpasses investigated were used by mammalians at least by fox, rabbit or marten. Because of the knowledge of the locations both of the maxima points of road mortality of wildlife and their use of controlled underpasses on is able to give recommendations for optimal localisations and dimensions of buildings which makes the wildlife able to pass the traffic line. The investigation proofs that the amount of wildlife killed on roads in Germany has been underestimated about 2000%. The problem of "just" wounded but not instantly killed animals while having an accident is pointed out as a severe problem from the animal welfare's point of view. PMID- 8205957 TI - [Remaining developments and status of animal welfare legislation]. AB - The author reports that in Germany animal welfare gets increasing importance in public opinion. He informs on the status of animal welfare legislation in the EU as well as in the Federal Republic of Germany. PMID- 8205958 TI - [International animal transport]. AB - The statement above explains, which measures could be taken to practise animal transportation considering the present legal situation in relation to crossing the boundaries. It should be practised in that way, that the animals don't suffer from harm or pain. To find a saver and more effective way also in accordance to the administration law, a national centralized regulation concerning transportation should be required. Therefore it has to be especially determined, that a temporal limit of 8 hours for transportation of animals which should be slaughtered will be achieved. PMID- 8205959 TI - [Ostriches--an agricultural domestic animal?]. AB - Since more than 100 years ostriches have been used as farm animals in South Africa. At present there are ca. 200 000 ostriches in 350 farms. Well known have been ostrich feathers which had formerly been equally previous (around 1900) as gold. Today, however, ostrich meat and leather are much appreciated. Since more than 10 years experiments with ostriches have been also carried out in other countries of the world, mainly in hot areas e. G. Australia, USA, Israel and Italy. Maybe the African ostrich will soon also belong to the daily life of animals bred and marketed in Germany. Since 1993 ca. 30 ostrich farms (with about 500 animals) have been known in Germany and a further 100 ostrich breeders in neighbouring countries. An additional many interested persons are looking forward to earn money through sales of eggs, chicks and breeding pairs. However, not everybody is farmer, some are rather well-to-do part-time or hobby-farmers who are speculating with these exotic wild birds. Anyway, at present business with breeding stock is booming. South Africa has prohibited the export and there are only few offers over here. A mature breeding ostrich at the age of 2-3 years costs about 10 000 DM. Since the animals use to live in small family units (one cock, two hens) the start of the breeding business begins at ca. 30 000 DM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8205960 TI - [Ferret husbandry]. AB - In order to give an assistance in the critical examination of the husbandry of ferrets a survey is given on the methods of keeping these animals as helpers for hunting, as house pets or as laboratory animals. The special claims of ferrets considering their care and housing are described. PMID- 8205961 TI - [Transgenic mice--biological fundamentals, practices and applications]. AB - The transfer of genes into the germline of mice has become a standard technique of modern biomedical research. In addition to direct microinjection of DNA into the pronuclei of fertilized mouse eggs, genes can now also be inactivated via homologous recombination in embryonic stem cells (gene targeting). In the future it will be possible to inactivate any cloned gene via homologous recombination in ES-cells and establish corresponding mouse mutants. PMID- 8205962 TI - [Biotechnology in veterinary medicine and animal production]. AB - The rapid development of modern biotechnology has introduced a new dimension to veterinary medicine and animal breeding. Genome analysis of important breeding species will ultimately allow to detect and consequently to eliminate any possible genetic disorder. Moreover, infectious diseases may also be detected easier and more reliable. The production of transgenic livestock opens the possibility to generate animals with improved health and productivity without time consuming breeding programmes. In the following review I will focus on the description of recent developments in the application of molecular biological techniques in veterinary medicine and animal production. Special emphasis will be given to the physiological consequences of transgene expression rather than the techniques for the production of transgenic animals. PMID- 8205963 TI - [Transgenic animals in experimental medicine]. AB - In this article the possibilities and limitations of transgenic animals in experimental medicine are discussed, guided by the following three questions: Which techniques have to be applied to produce transgenic animals? What can gene transfer and transgenic animals be used for? What ethical consideration have to be made in working with transgenic animals? PMID- 8205964 TI - [The effect of treatment with vitamin E or selenium on the course of salinomycin poisoning in swine]. AB - Experimentally induced salinomycin toxicosis in weanling pigs showed typical clinical signs of an intoxication with a polyether antibiotic. Severe ataxia and recumbency were the most prominent symptoms, which could be attributed to acute skeletal muscle necrosis by estimation of muscle enzyme activities (creatine kinase, aspartate aminotransferase) and histopathological examination. Intoxication had neither influence on concentrations of vitamin E and selenium dependent glutathione peroxidase in plasma and different organs nor on contents of fatty acids in skeletal muscles. No signs of increased lipid peroxidation in muscle tissue could be found. Prophylactic application of vitamin E or selenium one day before administration of salinomycin as well as treatment on the following days produced no protective effects. The treated pigs showed equal clinical and pathomorphological alterations as the untreated animals, although applications caused a significant increase of alpha-tocopherol and glutathione peroxidase concentrations in blood and different organs. PMID- 8205965 TI - [Monofrequency oscilloresistometry--possibilities and limits of a non-invasive method for respiratory resistance measurement in calves]. AB - The monofrequency forced oscillation technique (MFOT) has been found to be a simple, reproducible, fast and accurate method to carry out lung function testing in calves even under field conditions. If some technical as well as methodological requirements are taken into account, pulmonary or respiratory resistance can be assessed by means of the parameter oscillatory resistance (Ros). Furthermore, several Ros derived parameters are available for describing the functional status of the central bronchial system. Due to the low variability caused by methodological or intraindividual reasons, the MFOT represents a very qualified method for intraindividual studies. Comparing measuring results of different subjects, a higher biologically caused variance has to be taken into account. PMID- 8205966 TI - [Aflatoxicosis in Antwerp bearded bantams (Gallus gallus)]. AB - Aflatoxicosis is a worldwide disease especially of poultry and swine. The toxin is found frequently in different kinds of nuts and cereals from tropical areas. In the present report the cause of disease in "Antwerpener Bartzwergen" after unsuccessful treatments could be correlated with Aflatoxine in the amounts of 1629, 759, 5 and 5 micrograms/kg resp. for Aflatoxin B1, Aflatoxin G1, Aflatoxin B2 and Aflatoxin G2 in the groundnuts. PMID- 8205967 TI - [Urea and acetone content in milk as indicators for nutritionally caused fertility disorders of dairy cows]. AB - In 915 records of cows of the breeds German Simmental and German Brown the relationships between fertility parameters and milk urea as well as acetone content were analysed with linear models regarding systematic effects of herd, month, lactation number and breed-Brown-Swiss blood proportion. Milk urea concentration showed significant curvilinear associations to following fertility parameters: days open, days between first and last breeding as well as number of inseminations per service period, conception rate at first insemination after calving and lactational incidence of endometritis. The reproductive traits showed an optimum at a milk urea concentration between 15 and 25 mg/dl. The regression of the fertility parameters on acetone content in milk was nearly linearly decreasing and with the exception of days to first breeding after calving significantly different from zero. An increase of milk acetone by 0.01 mmol/l lead to a prolongation of days from first to last breeding in the service period by more than one day, and to a decrease of conception rate at first insemination by nearly one percent. An approach was developed which is suitable to quantify the influence of milk constituents on fertility traits. The model developed can consider nonlinear relationships, more than one metabolic parameter and systematic effects. Thresholds for milk parameters are no longer needed as the negative effects of the metabolic influences caused by nutritional factors are quantified in terms of fertility parameters. PMID- 8205968 TI - Effect of garlic on lead contents in chicken tissues. AB - Lead has been indicted to be involved in the aetiology of human and animal diseases. In view of earlier literature indicating that garlic antagonized lead toxicity, we have investigated the possible use of garlic feeding to clean up lead contents from chickens which had been exposed to natural or experimental lead pollution and consequently eliminate one of the sources of lead pollution to human consumers. Groups of chickens (10 birds each) were given lead alone (lead acetate equivalent to 5 mg lead/kg B.W.) or both lead and garlic simultaneously or lead followed by garlic post-treatment or garlic alone or distilled water. Lead concentrations were reduced in muscle and liver tissues of chickens given both lead and garlic simultaneously or as a post-treatment. Reduction in tissue lead concentrations were greater in birds given garlic as a post-treatment than those given garlic simultaneously with lead. The results indicate that garlic contain chelating compounds capable of enhancing elimination of lead. Garlic feeding can be exploited to safeguard human consumers by minimizing lead concentrations in meat of food animals which had been grown in a lead polluted environment. PMID- 8205969 TI - [The problem of recurrence of enzootic bovine leukosis in previously cured herds]. AB - Within nine months, enzootic bovine leukosis (EBL) occurred in 23 well documented herds. Eight of them (= 35%) had previously conducted the eradication programme as laid down by law. This proportion is tenfold higher than anticipated from the average incidence rate since 1978. The conclusion is drawn that a higher risk for reinfection exists for herds previously infected and cleaned than for those that never had leukosis before. For such cases hypotheses are presented. In one case clear evidence for one of the hypotheses was obtained. In case of re-occurrence of EBL in a previously cleaned herd it is proposed to examine the white blood picture of the sero-positive animals. If hematologically positive cattle are detected, they should be removed from the herd including their offspring. PMID- 8205971 TI - Short incus with intact tympanic membrane. PMID- 8205970 TI - [Pilot study of the occurrence of Chlamydia psittaci infections in commercial turkey flocks in Niedersachsen]. AB - Turkeys from 8 commercial flocks, of which were 6 clinically healthy, were examined by use of enzyme-linked immunosorbent assay systems for genus-specific Chlamydia antigens and also for antibodies against Chlamydia psittaci in 4 flocks. Results of the tests indicate the presence of Chlamydia psittaci infections in all 8 flocks. The percentage of combined cloacal and conjunctival swabs positive for Chlamydia antigen ranged from 20-91% [20-70%] whereas the percentage of antibody-positive serum samples ranged from 81-100%. Our findings suggest, that the prevalence of Chlamydia psittaci infections in clinically healthy turkey flocks is higher than hitherto suspected. PMID- 8205972 TI - Adult onset laryngeal papillomas. PMID- 8205973 TI - Endoscopic view of acute maxillary sinusitis. PMID- 8205974 TI - Beginner's guide to primary inhalant allergens. Part 1: Introduction to pollens. PMID- 8205975 TI - The Mayo Clinic experience with the cochlear implant. AB - The implantation of a cochlear electronic prosthetic device is an acceptable means of improving the communication ability of pre- and postlingually deafened children and adults. A significant number of patients in this series are in the senior citizen age group. It has been beneficial in improving communication ability in selected profoundly deafened individuals. There has been a significant improvement in the cochlear electronic prosthetic device since the initial report of Djourno in 1957. PMID- 8205976 TI - Multichannel cochlear implantation with percutaneous pedestal. AB - In a prospective study by Cohen et al, the superiority of multichannel cochlear implant patient performance over single-channel cochlear implant performance was demonstrated. The Ineraid system described in this paper includes a percutaneous pedestal which has had a satisfactory patient experience. Only one pedestal removal has been necessary because of specific pedestal problems. Other less serious pedestal problems decrease in frequency with increasing time post implantation. The auditory performance indicates significant communication skills improvement in patients with multichannel cochlear implants. PMID- 8205977 TI - Multichannel cochlear implant: pediatric age group. PMID- 8205978 TI - Surgical treatment and rehabilitation of prelingually and perilingually deafened children and adults with the nucleus multichannel cochlear implant. AB - We began our program in September 1992, using the Nucleus 22 Channel Cochlear Implant. To date, we have operated on four patients, one child with congenital hearing loss, two prelinguistically deaf adults and one perilingually deaf adult. Our results have shown a significant increase in auditory and speech reception and perception skills in the child. The perilingually deaf adult is able to understand speech in open set speech discrimination testing and, although we do not expect open set speech discrimination in the prelinguistically deaf adults, to date their results have been satisfactory. The two prelingually deaf adults are in an audiological rehabilitation program. Their response in prosodic aspects of speech and lipreading ability with sound have improved significantly. The only surgical complication was an infection of the flap in the child, but it was treated satisfactorily with i.v. penicillin. PMID- 8205979 TI - Bilateral digital hearing aids for binaural hearing. AB - The rehabilitation of binaural hearing performance in hearing impaired listeners has received relatively little attention to date. Both localization ability and speech-understanding-in noise are affected in the impaired listener. When localization performance is tested in impaired ears with conventional hearing aid fittings it is found to be worse than the unaided condition. Advances in electronic design now permit speculation about the implementation of complex digital filters within the confines of an in-the-ear hearing aid. We have begun exploring strategies to enhance the localization performance of impaired listeners with bilateral digital signal processing. We are examining three strategies in bilateral hearing aid design to improve localization performance in hearing impaired listeners, namely 1) more accurate fitting of individual ear losses, 2) equalization of the effect of the hearing aid itself on the acoustics within the ear canal, and 3) binaural fitting strategies which in effect modify individual ear fittings to enhance localization performance. The results of early psychophysical testing suggests that localization performance can be improved with these strategies. PMID- 8205980 TI - Performance of prelingually or postlingually deafened adults who were using a single or multichannel cochlear implant. AB - Long-term (two-year post-implantation) speech recognition was evaluated of prelingually and postlingually deafened adult cochlear implant users who had received either a single or a multichannel device. The patient group comprised 8 pairs of patients matched according to the onset and duration of deafness; in each pair one patient had an extra-cochlear single-channel implant and one had an intra-cochlear multichannel implant. A CDT (Continuous Discourse Tracking) test and a closed-set speech recognition test were used for speech recognition. The results of the postlingually deafened pairs of patients showed that the multichannel implant was superior to the single-channel implant, which is in agreement with other studies. In the pairs of prelingually deafened adult patients, the multichannel system was not found to be superior. This warrants further study and further application of single-channel implants in prelingually deafened patients. PMID- 8205981 TI - Experience with the multichannel intracochlear nucleus mini device in 24 postlingually deaf patients. PMID- 8205982 TI - Ionomeric cement--a bone glue for device fixation. AB - Ionocap, an ionomeric cement, is a new bone replacement material. Its generic name is polymaleinate ionomer, and it is an inert standardized biomaterial which is offered in a two component system. Since 1988 the ionomeric cement has been evaluated clinically in different situations. Its unique properties of biocompatibility, biostability and permanent adherence to bone make this new material very useful in head and neck surgery. PMID- 8205983 TI - Listening strategies and benefits when using a programmable hearing instrument with eight programs. AB - The main argument for purchasing a programmable hearing instrument with multiple programs is the assumption that different program settings can be used in acoustically different listening environments. The presumed advantages of the 3M Model 8200 programmable hearing instrument have been investigated in three clinical trials. This paper is a summary of the results. The evaluations were based on protocols and diary booklets where the patients indicated the selected listening situation versus program number. The Datalogging feature of the instrument, measuring the total on-time and the on-time per program, provided a unique support of the evaluation. The results indicated that most patients use 2 5 different programs, and have 2-4 programs fitted for their specific listening environments ("spotlight-listening"). It will, however, be difficult to develop general prescriptive formulas, as the listening pattern and environments differ across subjects. PMID- 8205984 TI - The current role of ERCP in the management of benign pancreatic disease. PMID- 8205985 TI - Cholangioscopy. PMID- 8205986 TI - Diagnostic laparoscopy. PMID- 8205987 TI - Therapeutic laparoscopy. PMID- 8205988 TI - Endoscopic ultrasonography. PMID- 8205989 TI - Electronic endoscopy, blood flow measurement and autofluorescence tissue spectroscopy. PMID- 8205990 TI - AIDS and gastrointestinal endoscopy. PMID- 8205991 TI - Complications of endoscopy. PMID- 8205992 TI - Diagnosis of esophago-gastric tumors. PMID- 8205993 TI - Preparation, premedication and surveillance in gastrointestinal endoscopy. PMID- 8205994 TI - Ulcers and gastritis. PMID- 8205995 TI - Treatment of esophageal varices. PMID- 8205996 TI - Endoscopic hemostasis in nonvariceal bleeding. PMID- 8205997 TI - Percutaneous endoscopic gastrostomy. PMID- 8205998 TI - Endoscopy of the small bowel: push, sonde and intra-operative. PMID- 8205999 TI - Inflammatory bowel disease. PMID- 8206000 TI - Colonic tumors. PMID- 8206001 TI - Diagnostic ERCP. PMID- 8206002 TI - Reflux disease and Barrett's oesophagus. PMID- 8206003 TI - Therapeutic biliary endoscopy. PMID- 8206004 TI - Rotational and translational motions of human spermatozoa: angle dependence of dynamic laser light scattering. AB - We have studied how the dynamic components of laser light scattered from human spermatozoa depend on the scattering angle. This was done by investigating the halfwidth of the intensity autocorrelation function. A model of the spermatozoa as freely rotating and translating linear objects was adequate to describe the scattered light. Rotational motions determined the halfwidth of the intensity autocorrelation function at very small scattering angles and contribution from translational motions was dominant at scattering angles larger than 20 degrees. The contribution from translational motions increased with increasing scattering angle. We found a nearly linear relationship between the translation speed and the rotation frequency. However, the ratio between the two properties varied more than expected from the methodological error. Therefore we introduced a propelling efficacy as a concept to describe the swimming efficiency. This property might contain important information about the swim characteristics. PMID- 8206005 TI - Implication of segment S45 in the permeation pathway of voltage-dependent sodium channels. AB - A 34-mer peptide, encompassing the S4 and S45 segments of domain IV of the electric eel voltage-dependent sodium channel, was synthesized in order to test the potential implication of S45 in the gating or permeation pathway. The secondary structure of peptide S4-S45 assessed by circular dichroism was found mainly helical, both in organic solvents and in lipid vesicles, especially negatively-charged ones. The macroscopic conductance properties of neutral and negatively-charged Montal-Mueller planar lipid bilayers doped with S4-S45 were studied and compared with those of S4. With regard to voltage-dependence, the most efficient system was S4-S45 in neutral bilayers. Voltage thresholds for exponential conductance development were found to correlate with the background or "leak" conductance. Assuming that the latter reflects interfacial peptide concentration, the mean apparent number of monomers per conducting aggregate could be estimated to be 3-5. In single-channel experiments, the most probable events had amplitudes of 8 pS and 5 pS in neutral and negatively-charged bilayers respectively. Ionic selectivity under salt gradients conditions, both at macroscopic and single-channel levels, was in favour of sodium ions (PNa/PK = 3). These properties compare favourably to previous reports dealing with peptide modelling transmembrane segments of voltage-dependent ionic channels. Specifically, when compared to S4 alone, the reduced unit conductance and the increased selectivity for sodium support the implication of the S45 region in the inner lining of the open configuration of sodium channels. PMID- 8206008 TI - Neuroimaging and Epilepsy: The Role of New Techniques. American Epilepsy Society Annual Course. Miami, Florida, December 5, 1993. PMID- 8206007 TI - Sensitivity of high-conductance potassium channels in synaptosomal membranes from the rat brain to intracellular pH. AB - High-conductance potassium channels have been studied in inside-out patches excised from proteoliposomes reconstituted from giant liposomes and rat brain synaptosomes. Acid pH in the medium reduced single channel current amplitude and increased the mean open probability and the frequency of channel opening. This was accompanied by a shortening of the open time constant at positive potential and by shortening of the longer closed time constant. The decrease of channel amplitude, the increase of the open probability and the decrease in the longer closed time constant can be explained by neutralization of negative charges of the membrane and by a decrease in the surface membrane potential which mimics membrane depolarization. The shortening of the mean open time is apparently due to a channel blockade by protons. PMID- 8206006 TI - Inactivation of voltage-dependent calcium current in an insulinoma cell line. AB - We have studied the mechanism of Ca current inactivation in the beta-cell line HIT-T15 by conventional and perforated patch recording techniques, using two pulse voltage protocols and a combination of current and tail current measurements. In 5 mM Ca, from a holding potential of -80 mV, the maximum current showed a complex time course of inactivation: a relatively fast, double exponential inactivation (tau h1 approximately 12 ms and tau h2 approximately 60 ms) and a very slowly inactivating component (tau > 1 s). The faster component (tau h1) was due to the voltage-dependent inactivation of a low-threshold activated (LVA), T-type current, which deactivates more slowly (tau approximately 3-5 ms) than the other components (tau approximately 0.2-0.3 ms). The intermediate component (tau h2) was due to the Ca-dependent inactivation of a portion of the high-threshold-activated (HVA) current. A saturating dose of the dihydropyridine (DHP) nifedipine (10 microM) did not affect the LVA current, but inhibited by 68 +/- 5% the transient, Ca-sensitive portion of the HVA current and by 33 +/- 12% the long lasting component. We suggest that three components of the calcium current can be resolved in HIT cells and the main target of DHPs is a HVA current, which inactivates faster than the DHP-resistant HVA component and does so primarily through calcium influx. PMID- 8206009 TI - Commentary: how has neuroimaging improved patient care? AB - Neuroimaging has significantly altered the management of patients with partial epilepsy. Magnetic resonance imaging (MRI) has been demonstrated to be a reliable and accurate indicator of the common pathologic findings underlying a partial seizure disorder. Intracranial mass lesions have been shown to be highly coherent with the localization of the epileptogenic zone. An MRI-identified epileptogenic lesion affects the selection of patients for epilepsy surgery and alters the diagnostic evaluation and the operative strategy. The results of the MRI preoperatively have prognostic importance in patients undergoing surgical treatment for partial epilepsy. Patients with lesional epileptic syndromes are considered favorable candidates for surgical ablative treatment. Hippocampal volume studies may predict the neurocognitive outcome in patients undergoing temporal lobe surgery. The use of MRI has resulted in a reduction in chronic intracranial EEG monitoring at most epilepsy centers, especially in patients with lesional pathology. MRI may be a reasonable initial "screening" procedure in selected patients with intractable partial epilepsy before consideration of a presurgical evaluation. A classification of partial epilepsy is proposed, based on the results of MRI, that may be useful for patients being considered for surgical treatment. Importantly, preoperative MRI must be correlated with the electrophysiologic studies and ictal semiology before decision-making regarding surgical therapy. PMID- 8206010 TI - Nuclear magnetic resonance spectroscopy of seizure states. AB - Magnetic resonance spectroscopy (MRS) can be used for noninvasive measurement of more than two dozen small metabolites in the brains of living animals and humans. In the first decade of its use for study of seizure phenomena in animals, MRS successfully detected in vivo seizure-induced cerebral acidosis and reduction of phosphocreatine concentration, changes that had been described previously by techniques requiring destruction of tissue. Thus validated, MRS was used to reveal new aspects of epileptic pathophysiology in animals: (a) dissociation of brain lactate and pH during experimental status epilepticus of low and intermediate intensity, reflecting metabolic compartmentation; and (b) long persistence of metabolically active elevated brain lactate after brief cortical electroshock. The latter phenomenon may be an extreme form of a mechanism by which lactate production primes synaptic terminals for maximal sustained firing rates during normal brain activation. Diffusion-weighted imaging of rat brain has shown that status epilepticus apparently shortens the mean path length of water diffusion, a novel finding that provides new insight concerning the physical conditions under which the seizure-related chemical changes detected by MRS occur. MRS study of epileptic patients has been undertaken more recently as instruments large enough for observations on humans have become available. Acidosis, reduction of phosphocreatine, and elevation of lactate have all been demonstrated in the human brain during seizure discharge. Chronic reduction of N acetylaspartate in limbic regions probably reflects neuronal loss and may correlate with mesial temporal sclerosis. PMID- 8206011 TI - New techniques in magnetic resonance and epilepsy. AB - Developments in magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and single photon emission tomography (SPECT) have opened new opportunities for noninvasive brain investigation. Functional imaging methods involving noninvasive MRI and minimally invasive PET and SPECT are available that allow investigation of brain abnormality in intractable epilepsy patients. Noninvasive techniques enable the investigation of many aspects of the underlying neuropathologic basis of intractable seizures and of the relationship of functional abnormalities both to structural abnormalities and to the seizure focus. New MRI techniques demonstrate the structure of the brain in fine detail (especially the hippocampus), provide information about the underlying metabolism of brain regions, and demonstrate functional activity of the brain with high spatial and temporal resolution. The clinical impact of this noninvasive information cannot be overstated and these techniques provide indispensable information to neurologists specializing in epileptology. The proper use and interpretation of the findings provided by these new technologies will be a major challenge to epilepsy programs in the next few years. PMID- 8206013 TI - Vascular malformations and epilepsy: clinical considerations and basic mechanisms. AB - Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology. PMID- 8206012 TI - MRI-based hippocampal volume measurements in epilepsy. AB - In the study of brain morphometry, it is accepted that a relationship exists between brain structure and function, both normal and abnormal. One descriptor of morphometric structure is volume. Abnormalities in hippocampal morphology, including unilateral or bilateral volume loss, are known to occur in epilepsy, Alzheimer's disease, and in certain amnestic syndromes. Precise quantitation should improve understanding of the role of any biologic system in normal function and in disease. The objectives of magnetic resonance (MR)-based hippocampal volume measurements are precise quantitation, identification of a normal range, and identification of the association between biologic variables and aberrations in this volumetric parameter. Volumetric measures introduce a level of precision in the estimation of hippocampal size that is not available simply by visually inspecting a set of MR images, thus enabling statistically based hypothesis testing. To produce accurate hippocampal volume measurements with magnetic resonance imaging (MRI), attention must be directed to the two major components of the operation as a whole, MR image acquisition and image processing. PMID- 8206014 TI - Magnetic resonance imaging in developmental disorders of the cerebral cortex. AB - Developmental disorders of the neocortex are commonly associated with epilepsy. The development of magnetic resonance imaging (MRI) has advanced our understanding of these disorders by permitting accurate recognition and clinical correlation during life. These disorders have multiple etiologies and are dependent on the time of injury to the developing nervous system. MRI has permitted the classification of these malformations in three major groups: generalized disorders, unilateral hemispheric, and focal disorders. Generalized disorders include lissencephaly, pachygyria, band heterotopia, and subependymal heterotopias. Hemimegalencephaly comprised the unilateral disorder. Focal lesions include focal cortical dysplasia, polymicrogyria, schizencephaly, and focal subcortical heterotopias. The information provided by MRI, in conjunction with the clinicoelectrographic features, is extremely important in the recognition of these syndromes and for the appropriate medical and surgical management of those patients with epilepsy. PMID- 8206015 TI - Operative strategies for patients with cortical dysplastic lesions and intractable epilepsy. AB - Cortical dysplastic lesions (CDLs) are usually identified by magnetic resonance imaging (MRI). Clinical, electrographic and histologic findings suggest that focal CDLs (FCDLs) are highly epileptogenic, often involve the rolandic cortex, and can present variable degrees of histopathologic abnormalities. An ictal or "ictal-like" bursting pattern of electrographic activity was recorded over dysplastic cortex in 65% of our patients. Resective surgery can eliminate or significantly reduce seizure frequency in many medically intractable patients, depending on lesion location, degree, and extent of histopathologic abnormalities. Best results are achieved when complete or major excision of both the MRI-visible lesion and the cortical areas displaying ictal electrographic activity can be performed. This is more likely when the degree of histopathologic abnormality is mild to moderate or when the lesion is in a temporal lobe. More severe histopathologic abnormalities and central insular or multilobar lesions usually lead to less favorable results: either major excision of the visualized lesion is impractical or the lesion is microscopically more extensive than shown by MRI. Multilobar resection or hemispherectomy for patients with infantile spasms associated with CDLs and for patients with hemimegalencephaly are often associated with dramatic improvement in seizure control. Callosotomy can be performed in selected patients with diffuse CDLs who have intractable drop attacks. PMID- 8206016 TI - The relative contributions of MRI, SPECT, and PET imaging in epilepsy. AB - Functional and structural neuroimaging techniques are increasingly indispensable in the evaluation of epileptic patients for localization of the epileptic area as well as for understanding pathophysiology, propagation, and neurochemical correlates of chronic epilepsy. Although interictal single photon emission computed tomography (SPECT) imaging of cerebral blood flow is only moderately sensitive, ictal SPECT markedly improves yield. Positron emission tomography (PET) imaging of interictal cerebral metabolism is more sensitive than measurement of blood flow in temporal lobe epilepsy. Furthermore, PET has greater spatial resolution and versatility in that multiple tracers can image various aspects of cerebral function. Interpretation of all types of functional imaging studies is difficult and requires knowledge of time of most recent seizure activity and structural correlates. Only magnetic resonance imaging (MRI) can image the structural changes associated with the underlying epileptic process, and quantitative evidence of hippocampal volume loss has been highly correlated with seizure onset in medial temporal structures. Improved resolution and interpretation have made quantitative MRI more sensitive in temporal lobe epilepsy, as judged by pathology. When judged by electroencephalography (EEG), ictal SPECT and interictal PET have the highest sensitivity and specificity for temporal lobe epilepsy; these neuroimaging techniques have lower sensitivity and higher specificity for extratemporal EEG abnormalities. Regardless of the presence of structural abnormalities, functional imaging by PET or SPECT provides complementary information. Ideally these techniques should be used and interpreted together to improve the localization and understanding of epileptic brain. PMID- 8206017 TI - Future directions for functional mapping. AB - The intracarotid amobarbital procedure and direct cortical stimulation are commonly used techniques for functional mapping in candidates for epilepsy surgery. The role of these two procedures has been challenged recently. Emerging technologies recently applied to functional mapping include optical imaging, functional positron emission tomography studies, transcranial magnetic stimulation, magnetoencephalography, and fast magnetic resonance imaging. Studies have used these new technologies and the potential for these procedures to replace the established but more invasive techniques is being considered. PMID- 8206018 TI - Neurobehavioral effects of power-frequency electromagnetic fields. AB - Some laboratory experiments have suggested that power-frequency electric and magnetic fields (EMF) may be capable of influencing calcium efflux from cell membranes, pineal function, and circadian rhythms. As yet, however, no consistent, replicable laboratory model has been developed for any of these effects. Most assessments of human volunteers exposed to EMF have been negative, but occasional effects on vigilance or alertness and some modest effects on circadian rhythmicity have been reported. Several carefully performed studies of workers occupationally exposed to high electric-field strengths have failed to find effects on behavior or cognitive functioning. Although the bulk of human research on the effects of EMF on cognitive performance is negative, there has been less assessment of behavior and psychiatric symptomatology. Because some studies, in both humans and animals, have described effects of EMF on circadian rhythms, future research might concentrate profitably on the assessment of EMF in relation to depression and other cyclically mediated psychiatric disorders. PMID- 8206020 TI - Health Effects Institute Environmental Epidemiology Planning Project. Papers dedicated to the memory of Dr. Richard D. Remington. PMID- 8206019 TI - Human adverse reproductive outcomes and electromagnetic field exposures: review of epidemiologic studies. AB - Concerns have been raised regarding a relation between residential and occupational electromagnetic (EM) field exposures and adverse reproductive effects. This paper reviews the epidemiologic evidence for this possible relation, including some pertinent methodologic issues, notes relevant findings from the experimental literature, and discusses areas for future research. Evidence is lacking for a strong association between a woman's use of a video display terminal (VDT) during pregnancy and spontaneous abortion. The evidence for a strong association between a women's use of a VDT and other adverse reproductive endpoints is also lacking, with some suggestive findings for congenital malformations and too few data to reach a conclusion about other endpoints. With respect to low-level EM field exposures other than VDTs, the paucity of data prevents one from determining whether there are reproductive health risks associated with such exposures. Therefore, this is an area that needs further investigation. Given that altered growth may be an underlying biologic effect of EM field exposures, endpoints that might be pursued in future studies include congenital malformations not associated with chromosomal anomalies, intrauterine growth retardation, and chromosomally normal spontaneous abortions. PMID- 8206021 TI - Assessing human exposure to power-frequency electric and magnetic fields. AB - This paper reviews published literature and current problems relating to the assessment of occupational and residential human exposures to power-frequency electric and magnetic fields. Available occupational exposure data suggest that the class of job titles known as electrical workers may be an effective surrogate for time-weighted-average (TWA) magnetic-field (but not electric-field) exposure. Current research in occupational-exposure assessment is directed to the construction of job-exposure matrices based on electric- and magnetic-field measurements and estimates of worker exposures to chemicals and other factors of interest. Recent work has identified five principal sources of residential magnetic fields: electric power transmission lines, electric power distribution lines, ground currents, home wiring, and home appliances. Existing residential exposure assessments have used one or more of the following techniques: questionnaires, wiring configuration coding, theoretical field calculations, spot electric- and magnetic-field measurements, fixed-site magnetic-field recordings, personal- exposure measurements, and geomagnetic-field measurements. Available normal-power magnetic-field data for residences differ substantially between studies. It is not known if these differences are due to geographical differences, differences in measurement protocols, or instrumentation differences. Wiring codes and measured magnetic fields (but not electric fields) are associated weakly. Available data suggest, but are far from proving, that spot measurements may be more effective than wire codes as predictors of long term historical magnetic-field exposure. Two studies find that away-from-home TWA magnetic-field exposures are less variable than at-home exposures. The importance of home appliances as contributors to total residential magnetic-field exposure is not known at this time. It also is not known what characteristics (if any) of residential electric and magnetic fields are determinants of human health effects. PMID- 8206022 TI - Problems and priorities in epidemiologic research on human health effects related to wiring code and electric and magnetic fields. AB - Because of a reported excess of cancers among children living near power lines, there is some concern that electric and magnetic fields (EMFs) induced by electric power sources may affect human health, and this possibility has provoked considerable controversy. The scientific question of whether there are such health effects is far from resolved. Building upon a set of detailed reviews of the available evidence, this paper proposes research priorities and places particular emphasis on epidemiologic research. The most pressing need is to verify the validity of the claim that childhood cancer risk is affected by the type of wiring code in the vicinity of the household. More useful work can be done to verify this in the areas in which such studies have already been carried out, and additional studies should be done elsewhere. Methodological investigation of the interrelationships among different measures and proxies for EMF is needed, and this could feed back to influence the type of EMF measures used in epidemiologic studies. Studies of cancer among adults in relation to EMFs in the work place are needed. Of lower priority are studies of adverse reproductive outcomes in relation to parental EMF exposure and studies of the neurobehavioral impact of chronic EMF exposure. This article also discusses the structural impediments of conducting environmental epidemiology research and argues that bold, large-scale epidemiologic monitoring systems are needed. There is a discussion of the interface between epidemiology and public policy in a topic area as controversial as EMFs. PMID- 8206023 TI - Introduction and recommendations: working group on indoor air and other complex mixtures. AB - Air in indoor and outdoor environments typically contains many gaseous and particulate pollutants that may affect adversely any individual at sufficiently high concentrations and more sensitive individuals at lower concentrations. The public health relevance of addressing the effects of mixtures is becoming increasingly evident as we improve the concept of total personal exposure to pollution and obtain more data from personal monitoring. The papers within this volume represent the deliberations of a working group assembled with the goal of improving the epidemiologic approach to investigating the health effects of indoor air pollution and other complex mixtures. The group, composed of epidemiologists, human and animal toxicologists, and experts on biomarkers, comprehensively reviewed the methodologic issues involved in investigating complex mixtures. Members noted the deficiencies of current epidemiologic methodology for studying complex mixtures and called for broad-based advances in study design, exposure assessment, outcome assessment, and data analysis and interpretation. Understanding the health effects of complex mixtures will require multidisciplinary research using not only epidemiologic studies incorporating the new methods of exposure assessment but animal and clinical toxicology. PMID- 8206024 TI - Assessment of health effects in epidemiologic studies of air pollution. AB - As we increasingly recognize the complexity of the pollutants in indoor and outdoor microenvironments, a broad array of inhaled mixtures has assumed scientific, public health, and regulatory importance. Few adverse effects of environmental pollutants are specific, that is, uniquely associated with a single agent; the adverse effects that might be considered in an investigation of the consequences of exposure to an inhaled complex mixture are generally nonspecific. In the context of this paper, we will refer to binary mixtures as complex, though we realize that a more precise definition of complexity would restrict the term to mixtures of three or more constituents. Their causes potentially include not only pollutant exposures through the medium of inhaled air but other environmental agents, such as infectious organisms and radiation, and inherent characteristics of the exposed persons, such as atopy. We review the outcome measures that have been used in epidemiologic studies of the health effects of single pollutants and complex mixtures. Some of these outcome measures have been carefully standardized, whereas others need similar standardization and modification to improve sensitivity and specificity for investigating the health effects of air pollution. PMID- 8206025 TI - Assessing exposures to inhaled complex mixtures. AB - In the course of daily activities, individuals spend varying amounts of time in different spaces where they are exposed to a complex mixture of gas, vapor, and particulate contaminants. The term complex is used in this paper to refer to binary mixtures as well as truly complex mixtures of three or more constituents. The diversity of the environments where pollution may occur, the number of pollutants that may be present, and the nature of the activity in the environment combine to pose a challenge to investigators of the health effects of air pollutants. This article discusses several methods of measuring or assessing exposure to complex mixture air contaminants that include time-activity assessments, personal monitoring, biomarkers of exposure, and microenvironmental models that can be employed singly or in combination in a protocol for exposure assessment. The use of nested designs, involving more intensive data collection from samples or subjects, is also considered. PMID- 8206026 TI - Complex mixtures and indoor air pollution: overview of epidemiologic methods. AB - The likelihood of an epidemiologic study correctly identifying an adverse health outcome associated with exposure to indoor air pollutants is increased if a) substantial variation exists in the frequency or level of exposure among study subjects otherwise at similar risk of the health outcome; b) the number of study subjects or study communities is large; c) the health outcome can be assessed with accuracy; d) relevant exposure levels can be measured with accuracy; e) an unbiased sample of exposed and nonexposed subjects is selected for study; and f) other determinants of the adverse health outcome can be measured. Nonetheless, given a strong enough impact of exposure to one pollutant or a mixture of pollutants on the risk of illness, it is possible for epidemiologic studies to discern a relation even if only some of the above circumstances are present. PMID- 8206027 TI - Epidemiological studies of neurotoxic, reproductive, and carcinogenic effects of complex mixtures. AB - Neurotoxic, reproductive, and carcinogenic effects are potentially important health end points in epidemiological studies of complex mixtures, particularly when such mixtures contain volatile organic compounds or trace metals. Epidemiological studies of neurotoxicity often will require direct clinical, behavioral, and/or physiological testing of study subjects, because these effects are likely to be subtle and not identifiable as clearly defined diseases. Peripheral nervous system toxicity can be assessed by clinical neurologic examinations, by electrophysiological tests of nerve conduction, and by physiological tests of thresholds for neurosensory perception, though these tests require considerable standardization for use outside the clinical setting, and most of the available tests have not been assessed for their utility in detecting effects of neurotoxic exposures. Neurobehavioral effects of exposures to solvents, as examples of complex mixtures, have been studied widely; but batteries of tests are often used, and these have not been well standardized and are generally unfamiliar to most research investigators in this area. Recently standardized neurobehavioral test systems developed by the World Health Organization and by a U.S. group for use in field studies, show promise in detecting neurobehavioral effects at relatively low environmental exposures. Similarly, new and sensitive measures of disturbed reproductive function, such as time-to-conception and biochemical indices of early pregnancy loss, are affected by some low-concentration environmental agents; but those measures have not yet been applied to studies of complex mixtures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206028 TI - Epidemiologic study design for investigating respiratory health effects of complex air pollution mixtures. AB - Epidemiologic studies of the respiratory health effects of air pollution are intrinsically difficult because exposure is common, expected effects at concentrations found in developed countries are weak, random misclassification of exposure is common, and the respiratory health indicators have multiple etiologies. Exposures to air pollutants also are multidimensional, generally consisting of a mixture of gases and particles. In this paper, epidemiologic study designs are described, and their potential for evaluating effects of complex pollutant mixtures are discussed. Power to detect the independent effects of individual pollutants in a complex pollutant mixture or to measure their interactions is in general very weak unless the study is specifically designed to test such hypotheses. However, with innovative and creative design, the independent and joint effects of multiple pollutants should be estimable in epidemiologic studies. PMID- 8206029 TI - Methodologic frontiers in environmental epidemiology. AB - Environmental epidemiology comprises the epidemiologic study of those environmental factors that are outside the immediate control of the individual. Exposures of interest to environmental epidemiologists include air pollution, water pollution, occupational exposure to physical and chemical agents, as well as psychosocial elements of environmental concern. The main methodologic problem in environmental epidemiology is exposure assessment, a problem that extends through all of epidemiologic research but looms as a towering obstacle in environmental epidemiology. One of the most promising developments in improving exposure assessment in environmental epidemiology is to find exposure biomarkers, which could serve as built-in dosimeters that reflect the biologic footprint left behind by environmental exposures. Beyond exposure assessment, epidemiologists studying environmental exposures face the difficulty of studying small effects that may be distorted by confounding that eludes easy control. This challenge may prompt reliance on new study designs, such as two-stage designs in which exposure and disease information are collected in the first stage, and covariate information is collected on a subset of subjects in state two. While the analytic methods already available for environmental epidemiology are powerful, analytic methods for ecologic studies need further development. This workshop outlines the range of methodologic issues that environmental epidemiologists must address so that their work meets the goals set by scientists and society at large. PMID- 8206030 TI - Biological markers of intermediate outcomes in studies of indoor air and other complex mixtures. AB - Biological markers of intermediate health outcomes sometimes provide a superior alternative to traditional measures of pollutant-related disease. Some opportunities and methodologic issues associated with using markers are discussed in the context of exposures to four complex mixtures: environmental tobacco smoke and nitrogen dioxide, acid aerosols and oxidant outdoor pollution, environmental tobacco smoke and radon, and volatile organic compounds. For markers of intermediate health outcomes, the most important property is the positive predictive value for clinical outcomes of interest. Unless the marker has a known relationship with disease, a marker response conveys no information about disease risk. Most markers are nonspecific in that various exposures cause the same marker response. Although nonspecificity can be an asset in studies of complex mixtures, it leads to problems with confounding and dilution of exposure-response associations in the presence of other exposures. The timing of a marker's measurement in relation to the occurrence of exposure influences the ability to detect a response; measurements made too early or too late may underestimate the response's magnitude. Noninvasive markers, such as those measured in urine, blood, or nasal lavage fluid, are generally more useful for field studies than are invasive markers. However, invasive markers, such as those measured in bronchoalveolar lavage fluid or lung specimens from autopsies, provide the most direct evidence of pulmonary damage from exposure to air pollutants. Unfortunately, the lack of basic information about marker properties (e.g., sensitivity, variability, statistical link with disease) currently precludes the effective use of most markers in studies of complex mixtures. PMID- 8206031 TI - Utility of controlled human exposure studies for assessing the health effects of complex mixtures and indoor air pollutants. AB - The study of health effects induced by exposure to mixtures of pollutants is a complex task. The purpose of this paper is to identify areas of research in which the conduct of human controlled exposure (clinical) studies may contribute to better understanding health effects of exposure to indoor air and other mixtures. The strengths and weaknesses of clinical studies in general are reviewed, as well as examples from the literature of approaches that have been used. Human chamber studies play an important role alongside epidemiologic and animal toxicologic studies in such research. Human chamber studies are limited with regard to assessing chronic effects, rare effects, or effects from long-duration exposures but are powerful in assessing acute, reversible effects from short-duration exposures in humans. The areas in which human chamber studies are most likely to contribute include identification of effects or markers of effects for exposure to a given pollutant or mix of pollutants; direct dose-response assessment of effects for individual compounds and mixtures of set composition; identification of individual compounds responsible for the effects of a mixture; study of the joint effects of a binary mixture; development of markers of acute exposure for particular compounds; development of outcome measurements to be used in the field; and identification, characterization, and testing of sensitive subpopulations. PMID- 8206032 TI - Introduction to working group on tropospheric ozone, Health Effects Institute environmental epidemiology planning project. AB - The working group on tropospheric ozone of the Health Effects Institute has evaluated the need for epidemiologic studies on the health effects of ozone (O3) exposure. This paper summarizes current data and identifies possible research questions. The extent to which ozone exposure results in chronic health effects is largely undefined and is the central issue for epidemiologic studies. Most current data focus on transient endpoints; the link between acute changes in symptoms and/or lung function and possible chronic effects has not been established. Concepts of ozone-induced health effects have been extended to include processes of chronic disease (e.g., markers of ongoing inflammation and repair, markers of accelerated lung aging). Traditional epidemiologic studies performed have focused only on accelerated lung aging and are limited by a number of methodologic problems. Recent, very preliminary, studies suggest new opportunities for the use of human lung tissue and a variety biological response markers as part of epidemiologic studies. The identification of sensitive subpopulations with regard to ozone-induced health effects has been studied incompletely and is important both in terms of study efficiency and mechanistic insight. Methodologic advances in the reconstruction of past ozone exposure are seen as essential, as is the incorporation of emerging markers of biologic response to ozone into traditional epidemiologic study designs. Finally, more data on the joint and independent contribution of other ambient air pollutants to putative ozone-induced health effects is warranted. PMID- 8206033 TI - Use of human lung tissue for studies of structural changes associated with chronic ozone exposure: opportunities and critical issues. AB - Definitive information on the chronic effects of exposure to ozone (O3) in humans is not available. There is a strong concern that ozone could produce chronic lung damage in humans on the basis that exposures are ubiquitous at levels that produce transient symptoms, function deficits, and lung inflammation in humans and chronic lung damage in laboratory animals. Both prospective and national population surveys suggest an association between chronic O3 exposure and reduced lung function, and a pilot investigation of autopsied lungs of accident victims in Los Angeles reported an unexpectedly high incidence of disease in the centriacinar region, the lung region known to receive the highest dose of inhaled O3. This paper discusses the advantages and limitations of further studies of structural changes in human lung tissue in relation to chronic O3 exposure. The major advantages of such studies are that a) measurable effects may be related to realistic chronic exposures, b) the effects may be described quantitatively and compared directly to those obtained in chronic animal inhalation exposures, and c) evidence for chronic effects may be obtained much more rapidly than in prospective studies. The major limitations are the difficulties in obtaining sufficient reliable information on residential history, physical activity out-of doors, and smoking and other confounding exposures to lung irritants from next of kin, and limited availability of adequate air quality data for determining ambient concentrations at places of residence and/or outdoor exercise. The paper also discusses approaches to minimizing these limitations in the design of specific studies. PMID- 8206034 TI - Examining acute health outcomes due to ozone exposure and their subsequent relationship to chronic disease outcomes. AB - Current evidence indicates that individuals exposed to short term elevations in ambient ozone may experience both upper and lower respiratory effects. Some respiratory symptoms and spirometric changes are mild and reversible in nature, while others involve more severe outcomes, including hospital admissions and emergency room visits. However, many questions remain about the effects of acute ozone exposure and the implications of this exposure for chronic disease outcomes. For example, the identification of sensitive subgroups, the delineation of the entire spectrum of health effects due to exposure to ozone, the potential synergy between viral infections and ozone exposure, and the nature of adaptation to ozone are not well characterized. In addition, studies that examine the association between acute responses to ozone and potential biological indicators of a chronic disease process would be desirable. This paper serves to provide an overview of the types of epidemiologic studies that may be appropriate and factors to consider in addressing these questions. PMID- 8206035 TI - Detection of chronic respiratory bronchiolitis in oxidant-exposed populations: analogy to tobacco smoke exposure. AB - Studies in nonhuman primates indicate that one pathophysiologic consequence of ozone exposure is chronic bronchiolitis in terminal bronchioles. Modeling dosimetry suggests that a similar phenomenon is possible in humans. These findings may constitute an important analogy to the respiratory bronchiolitis that is associated with tobacco smoking in young adults. This analogy could form the basis for future research related to chronic respiratory health effects of ozone. The smoking data are reviewed and several research strategies are proposed that will be developed more fully in subsequent articles in this volume. PMID- 8206036 TI - The role of ozone exposure in the epidemiology of asthma. AB - Asthma is a clinical condition characterized by intermittent respiratory symptoms, nonspecific airway hyperresponsiveness, and reversible airway obstruction. Although the pathogenesis of asthma is incompletely understood, it is clear that airway inflammation is a paramount feature of the condition. Because inhalation of ozone by normal, healthy subjects causes increased airway responsiveness and inflammation, it is somewhat surprising that most controlled human exposure studies that have involved asthmatic subjects have not shown them to be especially sensitive to ozone. The acute decrement in lung function that is the end point traditionally used to define sensitivity to ozone in these studies may be due more to neuromuscular mechanisms limiting deep inspiration than to bronchoconstriction. The frequency of asthma attacks following ozone exposures may be a more relevant end point. Epidemiologic studies, rather than controlled human exposure studies, are required to determine whether ozone pollution increases the risk of asthma exacerbations. Asthma affects approximately 10 million people in the United States and, thus, the answer to this question is of considerable public health importance. Both the prevalence and severity of asthma appear to be increasing in many countries. Although increased asthma morbidity and mortality are probably of multifactorial etiology, a contributory role of urban air pollution is plausible. The epidemiologic database to support an association between asthma and ozone exposure is limited, but the results of several studies suggest such an association. Some potential approaches to further investigation of the relationship between asthma and ozone, including those that would link controlled human exposures to population-based studies, are considered. PMID- 8206039 TI - Design and analysis of studies of the health effects of ozone. AB - The design and analysis of studies that investigate the effect of exposure to ozone on health outcomes need to define carefully the methods for the assessment of the exposure and to determine precisely which is the outcome of biological relevance. The estimation of sample size for longitudinal studies requires the expected rates of change among the exposed and unexposed, the variance of the outcome, and the correlation of measurements taken within an individual. Methods of analysis whose primary interest is in the combination of cross-sectional studies for the determination of the marginal distribution of the outcome are particularly appropriate for biological processes where the effect of exposure is acute. Conditional models are particularly useful for investigating the effect of changes in exposure on changes in outcome at the individual level. In addition, conditional models incorporate a dampening effect of exposure that may provide a reasonable agreement with several biological mechanisms. The identification of susceptible individuals and the description of the behavior of their outcomes over time may be better accomplished by using the within-individual variance as the outcome of interest. Discrepancies of the within- and between-individual regressions may be suggestive of chronic effects, and methodological research in this area is needed. Studies of the health effects of ozone exposure need to address the incorporation of missing data, measurement error, and the combination of complementary studies. PMID- 8206037 TI - Identification of subpopulations that are sensitive to ozone exposure: use of end points currently available and potential use of laboratory-based end points under development. AB - A number of epidemiological studies have attempted to assess the effect of recurrent ozone exposure in humans. For the most part, they have failed to document convincingly an association between chronic ozone exposure and differences in lung function performance or respiratory symptoms. This is not surprising given the small respiratory effects observed in animals chronically exposed to ozone and assuming that people with abnormal respiratory function resulting from other occupational or environmental exposures, such as tobacco smoke, would make up a much larger percentage of the population than people with respiratory effects attributable to ozone. Therefore, either more sensitive end points must be developed to detect subtle changes due to chronic ozone exposure, or ways of selecting subpopulations that are especially sensitive to ozone must be devised. It has been well documented that there are large and reproducible differences in the acute response of individuals to ozone as measured by pulmonary function tests. Recently, it has also been shown that there are large differences in the acute response of individuals to ozone as measured by inflammatory and other biochemical parameters. This paper discusses the problems of selecting individuals who are sensitive to ozone depending on the end point chosen. It also describes potential new sensitive end points that might be available for ozone epidemiology studies in the near future. PMID- 8206038 TI - Principles of study design in environmental epidemiology. AB - This paper discusses the principles of study design and related methodologic issues in environmental epidemiology. Emphasis is given to studies aimed at evaluating causal hypotheses regarding exposures to suspected health hazards. Following background sections on the quantitative objectives and methods of population-based research, we present the major types of observational designs used in environmental epidemiology: first, the three basic designs involving the individual as the unit of analysis (i.e., cohort, cross-sectional, and case control studies) and a brief discussion of genetic studies for assessing gene environment interactions; second, various ecologic designs involving the group or region as the unit of analysis. Ecologic designs are given special emphasis in this paper because of our lack of resources or inability to accurately measure environmental exposures in large numbers of individuals. The paper concludes with a section highlighting current design issues in environmental epidemiology and several recommendations for future work. PMID- 8206040 TI - Summary of papers and research recommendations of Working Group on Tropospheric Ozone, Health Effects Institute environmental epidemiology planning project. AB - This paper summarizes the themes and recommendations that emerge from the papers presented by the Working Group on Tropospheric Ozone. In terms of current knowledge, the following are considered of particular importance: a) lack of clear evidence for a human analogue of the terminal bronchiolar and proximal acinar changes observed in the lungs of ozone-exposed animals; b) lack of evidence for a connection between the acute respiratory effects of O3 and possible chronic respiratory effects; c) need to better define the characteristics of O3-susceptible individuals; d) the lack of adequate exposure assessment tools for reconstruction of lifetime O3 exposure; and e) incomplete information on the role of other ambient environmental pollutants in the facilitation of O3 effects or as a cause of effects attributed to O3 in human populations. Based on the above, several recommendations for epidemiologic research on health effects of O3 are offered. a) Studies to investigate the existence of chronic health effects of O3 are essential, particularly those that include autopsied human lung tissue and biologic and physiologic response markers. b) Studies are needed to link acute responses with chronic effects and should include joint epidemiologic and controlled-exposure assessments. c) Studies are needed to identify susceptible subgroups. Such studies should include newly emerging biologic markers of O3 exposure. d) Accurate and precise tools for chronic O3 exposure assessment need to be developed for use in retrospective and prospective studies. e) Collaborative studies between epidemiologists and laboratory investigators are needed to develop and evaluate markers of O3 exposure and to test O3 exposure models. PMID- 8206041 TI - Methodologic research needs in environmental epidemiology: data analysis. AB - A brief review is given of data analysis methods for the identification and quantification of associations between environmental exposures and health events of interest. Data analysis methods are outlined for each of the study designs mentioned, with an emphasis on topics in need of further research. Particularly noted are the need for improved methods for accommodating exposure assessment measurement errors in analytic epidemiologic studies and for improved methods for the conduct and analysis of aggregate data (ecologic) studies. PMID- 8206042 TI - Measurement issues in environmental epidemiology. AB - This paper deals with the area of environmental epidemiology involving measurement of exposure and dose, health outcomes, and important confounding and modifying variables (including genotype and psychosocial factors). Using examples, we illustrate strategies for increasing the accuracy of exposure and dose measurement that include dosimetry algorithms, pharmacokinetic models, biologic markers, and use of multiple measures. Some limitations of these methods are described and suggestions are made about where formal evaluation might be helpful. We go on to discuss methods for assessing the inaccuracies in exposure or dose measurements, including sensitivity analysis and validation studies. In relation to measurement of health outcomes, we discuss some definitional issues and cover, among other topics, biologic effect markers and other early indicators of disease. Because measurement error in covariates is also important, we consider the problems in measurement of common confounders and effect modifiers. Finally, we cite some general methodologic research needs. PMID- 8206044 TI - The place of epidemiology in environmental decisions: needed support for the development of risk assessment policy. AB - Some of the most challenging problems in the use of epidemiology for regulatory policy concern summarizing epidemiological and other kinds of information to create a weight of evidence. Another frequent issue is whether to embark on epidemiological study. There are also concerns that negative results never see the light of day. These and other meta-issues are worthy of funded evaluation by expert work groups. PMID- 8206043 TI - Basic problems in interaction assessment. AB - This paper reviews problems with the definition and estimation of interactions in epidemiologic studies. Methods for modeling interactions and dose-response also are reviewed, and references to more detailed literature are provided. Concepts are illustrated in the context of evaluating the joint effects of household radon exposure and environmental tobacco smoke. PMID- 8206045 TI - Introduction to power-frequency electric and magnetic fields. AB - This paper introduces the reader to electric and magnetic fields, particularly those fields produced by electric power systems and other sources using frequencies in the power-frequency range. Electric fields are produced by electric charges; a magnetic field also is produced if these charges are in motion. Electric fields exert forces on other charges; if in motion, these charges will experience magnetic forces. Power-frequency electric and magnetic fields induce electric currents in conducting bodies such as living organisms. The current density vector is used to describe the distribution of current within a body. The surface of the human body is an excellent shield for power-frequency electric fields, but power-frequency magnetic fields penetrate without significant attenuation; the electric fields induced inside the body by either exposure are comparable in magnitude. Electric fields induced inside a human by most environmental electric and magnetic fields appear to be small in magnitude compared to levels naturally occurring in living tissues. Detection of such fields thus would seem to require the existence of unknown biological mechanisms. Complete characterization of a power-frequency field requires measurement of the magnitudes and electrical phases of the fundamental and harmonic amplitudes of its three vector components. Most available instrumentation measures only a small subset, or some weighted average, of these quantities. Hand-held survey meters have been used widely to measure power-frequency electric and magnetic fields. Automated data-acquisition systems have come into use more recently to make electric- and magnetic-field recordings, covering periods of hours to days, in residences and other environments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206046 TI - Epidemiologic studies of electric and magnetic fields and cancer: strategies for extending knowledge. AB - Epidemiologic research concerning electric and magnetic fields in relation to cancer has focused on the potential etiologic roles of residential exposure on childhood cancer and occupational exposure on adult leukemia and brain cancer. Future residential studies must concentrate on exposure assessment that is enhanced by developing models of historical exposure, assessment of the relation between magnetic fields and wire codes, and consideration of alternate exposure indices. Study design issues deserving attention include possible biases in random digit dialing control selection, consideration of the temporal course of exposure and disease, and acquisition of the necessary information to assess the potential value of ecologic studies. Highest priorities are comprehensive evaluation of exposure patterns and sources and examination of the sociology and geography of residential wire codes. Future occupational studies should also concentrate on improved exposure assessment with increased attention to nonutility worker populations and development of historical exposure indicators that are superior to job titles alone. Potential carcinogens in the workplace that could act as confounders need to be more carefully examined. The temporal relation between exposure and disease and possible effect modification by other workplace agents should be incorporated into future studies. The most pressing need is for measurement of exposure patterns in a variety of worker populations and performance of traditional epidemiologic evaluations of cancer occurrence. The principal source of bias toward the null is nondifferential misclassification of exposure with improvements expected to enhance any true etiologic association that is present. Biases away from the null might include biased control selection in residential studies and chemical carcinogens acting as confounders in occupational studies. PMID- 8206048 TI - Fabric softeners and softness perception. AB - In order to evaluate the efficiency of various commercial chemical fabric softeners, a technique of obtaining subjective assessment known as 'magnitude estimation' was used to estimate the fabric softness. Particular emphasis was given to subjective scaling and limits of human perception. Comparison between softness and compression (a physical measure) was demonstrated. PMID- 8206047 TI - Biologically based epidemiological studies of electric power and cancer. AB - As societies industrialize, the health profile of the population changes; in general, acute infectious disease declines and chronic disease increases. Use of electricity is a hallmark of the industrialization process, but there has been no suspicion that electricity could increase the risk of cancer. Recently, however, a number of epidemiologic studies have suggested that electromagnetic fields (EMF) may do just that. Although few cancer experiments have been done yet, there are a number of biological effects of EMF reported in the literature that might provide bases for designing cancer experiments and epidemiologic studies. These include effects of EMF on: a) DNA transcription and translation, b) calcium balance in cells, and c) pineal production of melatonin. Alterations in DNA transcription and translation could have pleiotropic effects. Disruption of calcium homeostasis has many implications including oncogene activation, promotional activity via protein kinases and ornithine decarboxylase (ODC), and increasing oxidative stress. Reduction of melatonin suggests a possible increased risk of cancers of hormone-dependent tissues such as breast and prostate. The idea that a cancer-causing agent must either be an initiator or a promoter should be discarded; indeed, the phenomenologic meaning of these two terms has become confused with imputed mechanistic necessity in recent years. Agents that affect division of normal cells or of fully transformed cells can play an important role in clinical cancer development quite apart from initiation or promotion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206049 TI - Ergonomic guidelines for the prevention of discomfort of static postures based on endurance data. AB - This communication aims to show why guidelines to prevent discomfort of static postures can be based on endurance data, and to give insight in the aim and scope of a recent 'work-rest model for static postures' (WR model). The paper is a response to a recent paper of Mathiassen and Winkel (1992) who questioned the usefulness of discomfort and endurance data, and of the WR model for developing guidelines for static postures. It is concluded that discomfort can be considered as an independent evaluation variable for working postures, anchored in European legislation. Discomfort can be predicted from the 'remaining endurance capacity' (REC) because of a known relationship between the REC and discomfort as measured with the Borg rating scale. The WR model estimates at group level the mean REC of a static posture with or without an external force during and immediately after a work-rest schedule. The WR model is meant to assist practitioners in the assessment and optimization of static postures (and external forces) and work rest schedules in order to avoid high levels of discomfort. PMID- 8206050 TI - The analysis of thermal comfort requirements through the simulation of an occupied building. AB - Building simulation usually focuses on the study of physical indoor parameters, but we must not forget the main aim of a house: to provide comfort to the occupants. This study was undertaken in order to build a complete tool to model thermal behaviour that will enable the prediction of thermal sensations of humans in a real environment. A human thermoregulation model was added to TRNSYS, a building simulation program. For our purposes, improvements had to be made to the original physiological model, by refining the calculation of all heat exchanges with the environment and adding a representation of clothes. This paper briefly describes the program, its modifications, and compares its results with experimental ones. An example of potential use is given, which points out the usefulness of such models in seeking the best solutions to reach optimal environmental conditions for global, and specially local comfort, of building occupants. PMID- 8206051 TI - Sleep patterns, shiftwork, and individual differences: a comparison of onshore and offshore control-room operators. AB - The sleep patterns of offshore control-room operators were compared with those of personnel carrying out similar work onshore, taking into account individual differences in age, number of years of shiftwork, and neuroticism. The dependent variables were self-reported sleep quality and duration for day-shift (D-S) and night-shift (N-S) work, and during leave periods (L-P). Offshore workers reported longer N-S sleep duration, and lower D-S sleep quality than those onshore, but the two groups did not differ in L-P measures. The effects of environmental differences (onshore versus offshore) on sleep patterns were more marked than those of the two different shift systems (weekly rotation and fast rotation) in operation onshore. Age was negatively related to both duration and quality of sleep; over and above age, number of years of shiftwork was negatively related to sleep duration. Neuroticism was also negatively related to sleep duration and, more strongly, to sleep quality. These findings are discussed in relation to the literature on shiftwork and sleep in general, and the characteristics of the offshore environment in particular. PMID- 8206053 TI - The effects of two different kinds of quilt on human core temperature during night sleep. AB - Effects of two kinds of quilt with different thermal insulation properties between the upper and lower halves on human core temperature during night sleep were compared at an ambient temperature of 16 degrees C and a relative humidity of 50% in five healthy adult women. One quilt has a thick part (110 mm) in the upper half and a thin part (63 mm) in the lowest half (Quilt A), and the other has a thin part (63 mm) in the upper half and a thick part (110 mm) in the lower half (Quilt B). Subjects, wearing shirts with half-sleeves and breeches, slept on a bed with sleeping mat, being fully covered by either Quilt A or Quilt B from 22:00 to 06:00. The major finding was that rectal temperature fell more quickly in Quilt B after retiring at 22:00, being kept at a lower level during one third of the whole night. We suggest that the reduced level of rectal temperature in Quilt B might be ascribed to lower thermal insulation in the upper half side of the Quilt B and partly to different core-peripheral blood redistribution in the lower extremities between the two kinds of quilt. Rapid fall and lowered level rectal temperature in Quilt B might be of significance for ease in sleep onset and sleep depth. PMID- 8206052 TI - Heart rate strain indices in Greek steelworkers. AB - The heart rate strain of 14 Greek steelworkers was assessed during the winter and summer months of 1989 and 1990. Activity sampling was used to establish the pattern of work performed and heart rates were measured throughout work shifts. In addition, maximum aerobic capacity was estimated. The mean heart rate during work was 97 bt.min-1 (+/- 13), while the mean relative heart rate increase was 21% (+/- 15%). The results indicated that the work performed could be classified as light to moderate. PMID- 8206054 TI - The effect of aerodynamic handlebars on oxygen consumption while cycling at a constant speed. AB - In this study, the oxygen consumption (VO2) of bicycling was measured at a fixed speed (40 km.h-1), on level terrain, with normal and aerodynamic handlebars using a Douglas bag collection system. Eleven elite (USCF category 1 or 2) men cyclists age 24 to 40 years (mean = 28.5, SD +/- 4.6) performed four consecutive (two with each bar in alternating order) steady state rides at 40 km.h-1 over a 4 km flat course (same direction each trial). Expired gases were collected in a 1501 Douglas bag attached to a following vehicle during the last 45 s (approx. 0.5 km) of each trial. A repeated measures analysis of variance revealed a significant (p < 0.02) handlebar effect. Specifically, VO2 was 2% lower under the aerodynamic handlebar treatment (mean = 4.26, SD +/- 0.36 l.min-1) when compared with that of the normal handlebar treatment (mean = 4.34, SD +/- 0.35 l.min-1). The results of this study demonstrate that the reported aerodynamic advantage of the aerodynamic handlebars produces a small but significant reduction in the VO2 of bicycling at 40 km.h-1. PMID- 8206055 TI - The effect of scale-side, indicator type, and control plane on direction-of-turn stereotypes for Hong Kong Chinese subjects. AB - This study investigates the influence of scale-side, pointer type, direction-of increase, and control plane on direction-of-turn stereotypes for Chinese subjects using a variety of configurations of a linear display with a rotary control. Pointer type and direction of increase did not have a significant effect on direction-of-turn expectation. Strong stereotypes are found when Warrick's principle and the scale-side principle do not clash. In such a configuration, the scale is on the opposite side of the display to the control, and the display indicator moves in the same plane as the control. However, when the two principles clash, stereotypes are weakened or eliminated and no single principle dominates. For a rotary control placed to the right of a horizontal linear scale in the frontal plane there are strong clockwise-for-right and counterclockwise for-left stereotypes which dominate the scale-side principle when there is a clash. The most marked stereotypes and fastest response times are obtained for the horizontal display with the control in the same frontal plane. PMID- 8206056 TI - Absorption of vibration energy in the human hand and arm. AB - A possible basis for the risk assessment for hand-transmitted vibration may be to determine the amount of energy absorbed in the human hand and arm. In the present study, the mechanical energy absorption in the hand-arm system was measured within the frequency range of 4 to 1000 Hz. The study was carried out on ten healthy subjects during exposure to sinusoidal vibration. The influence of various experimental conditions, such as vibration direction (Xh, Yh, Zh), grip force (25-75 N), vibration level (8-45 mm/srms), and hand-arm posture were studied. The outcome shows that the energy absorption in the human hand and arm depended mainly on the frequency and direction of the vibration stimulus. Higher vibration levels, as well as firmer handgrips, resulted in higher absorption of energy. Varying hand-arm postures had only a small influence on the amount of absorbed energy, while the constitution of the hand and arm affected the energy absorption to a larger extent. PMID- 8206057 TI - An assessment of neck and upper extremity disorders by questionnaire and clinical examination. AB - To study the usefulness of a screening questionnaire for neck/upper extremity complaints, 165 women in either repetitive industrial, or mobile and varied work, were studied by the questionnaire and by a detailed clinical physical examination. A total of 94 subjects recorded complaints in the questionnaire. In 140 subjects findings were recorded at the examination. Most subjects with findings at the clinical examination of shoulders reported complaints in the questionnaire (sensitivity 80%). For the other anatomical regions, the sensitivity was rather low (42-65%). For all regions, most subjects without findings reported no complaints (specificity 77-97%). A total of 75 subjects were given clinical diagnoses according to a set of predetermined diagnostic criteria. The capacity of the questionnaire to identify diagnoses of shoulders was higher (sensitivity 92%) than for the other regions (66-79%). Of subjects who did not qualify for diagnosis, a majority (specificity 71-81%) did not report complaints in the questionnaire. We conclude that the questionnaire approach gives a fairly good picture of the neck/upper extremity status of a working female population. However, a clear view of the size of a problem is obtained only by a detailed clinical examination, particularly as regards the neck, elbows and hands, for which the questionnaire gave an underestimate. PMID- 8206058 TI - The effect of night-time naps on recovery from fatigue following night work. AB - A questionnaire was performed in order to investigate the effect of naps during duty on recovery from fatigue. Studies were performed on 12 male computer operators in each of two chemical plants working a four-team three-shift system. In one of the plants, the shift workers were able to take a 2 h nap during the night shift (nap group). In the other plant, no nap was taken (no-nap group). Before and after the two consecutive night shifts, both the nap and no-nap groups greatly extended their night sleeps, but the daytime sleep taken by the no-nap group during this period was significantly longer than that of the nap group on both the first and second days. No significant difference was found when comparing the length of the day sleep of the no-nap group with the total sleeping time (night-time nap plus subsequent day sleep) of the nap group. Therefore a night-time nap enables part of the essential sleep to be taken in advance of the day sleep following night work. During night work, both the nap and no-nap groups exhibited an increase in the sleepiness scores and also in the subjective feelings of fatigue concerning the complaints related to drowsiness, dullness and difficulty in concentration. However, it was found that for the no-nap group these effects continued for a large part of the recovery period following night work. It can therefore be surmised that naps taken during night-time work can be to a certain extent aid recovery from the fatigue caused by that work. PMID- 8206059 TI - An OWAS-based analysis of nurses' working postures. AB - The working postures of Dutch nurses (n = 18) in an orthopaedic ward and a urology ward were observed using the Ovako Working posture Analysis System (OWAS). During observation, both working postures and activities were recorded. A specially developed computer program was used for data analysis. By means of this program, it was possible to calculate the working posture load for each activity and the contribution of a specific activity to the total working posture load. This study shows that some activities of the nurses in both wards were performed with poor working postures. In the orthopaedic (resp. urology) ward two (resp. one) out of 19 observed postures of parts of the body were classified as Action Category 2. Moreover, 20% (resp. 16%) of the so-called typical working postures was classified in Action Category 2. This suggests, that in both wards working postures that are slightly harmful to the musculoskeletal system, occur during a substantial part of the working day. Differences between both wards with respect to working posture load and time expenditure were determined. Activities causing the workload to fall into OWAS higher Action Categories were identified. The data show that poor working postures in the nursing profession not only occur during patient handling activities but also during tasks like 'administration'. Focusing on patient-handling (i.e., lifting patients) in order to determine the load on the musculoskeletal system would therefore lead to an underestimation of the total working posture load of nurses. PMID- 8206060 TI - An evaluation of patient lifting techniques. AB - In the present laboratory study five two-person manual lifting techniques were evaluated as to the amount of physical exertion required of the nurses. Ten female volunteers served as nurses; two healthy volunteers (weight: 55 kg and 75 kg) served as passive patients. The working postures and motions were recorded on videotape. The data thus obtained were used in a anatomical-biomechanical analysis. The perceived exertion by the nurses was measured as well. In almost all situations the compressive forces on the nurse's spine exceeded their acceptable limit of 3425 N. Differences between the lifting techniques were most obvious when the 55 kg patient was lifted. Ratings of the perceived exertion (RPE scores) were higher in symmetrical handling than in asymmetrical handling. The three techniques using asymmetrical hand positions produced less subjective stress. RPE scores and rotation of the back were negatively correlated. Rotating the back when moving a patient from one side to the other seems to ease the task. On the whole, the results of the biomechanical evaluation are in line with the subjective perception of the nurses. In both instances the barrow lift appeared to be the most strenuous one; the Australian lift resulted in low compressive forces and a moderate level of perceived exertion. PMID- 8206061 TI - Initial training as a stimulus for optimal physical fitness in firemen. AB - In this investigation the physical fitness of 34 recruits to the UK Fire Service was assessed before and after their initial training (tests 1-2) and on three occasions (tests 3-5) during the first 18 months of their service (n = 34 + 6 = 40). The initial training (test 2-test 1) resulted in an increase in maximum aerobic power (11% p < 0.05), body mass (2 kg, p < 0.001), lean body mass (2.02 kg, p < 0.001), grip and lifting strengths (p < 0.001), and in calf girth (p < 0.05). But no change in waist girth, maximum anaerobic power or measures of lung function was noted. There was evidence therefore that the men became physically fitter. In the first eighteen months of their service, subjects' maximum oxygen consumption declined to pre-training levels, while body mass continued to increase with a decrease in lean body mass (p < 0.001). Strength remained unaltered or tended to fall with a decrease in calf girth (p < 0.05). These changes reflected a return towards pre-training physical fitness levels. It is suggested that the initial training, while ill-matched to the firemen's habitual activity, produced levels of physical fitness which may approximate more closely to the infrequent peak requirements experienced by the men during actual fire fighting. Consequently it is concluded that the physical training during service was insufficiently intense and that a more effective programme could be designed to maintain an appropriate level of physical fitness. PMID- 8206062 TI - The perception of physical fitness as a guide to its evaluation in firemen. AB - There is increasing interest in the acquisition and measurement of physical fitness in general populations (Bassey and Fentem 1981). Measuring fitness can be uncomfortable and exhausting for subjects and expensive and time-consuming for experimenters (Andersen et al. 1971). Various authors have described and/or evaluated methods for the prediction of VO2 max (Astrand and Rhyming 1954, Davies 1968, Fitchett 1985, Harrison et al. 1980, Jette 1979, Jette et al. 1982, Shephard 1975, Shephard et al. 1979). A valid, safe, socially-acceptable alternative for such measurements applicable to a population would be of benefit. Asking subjects how they perceive their own physical fitness might be such an alternative. The validity and reliability of the data contained from such a questionnaire could be tested against conventional measures of physical fitness. A study which incorporated questionnaire surveys as one method of determining physical fitness in a large population was undertaken on Fire Service personnel in England, Scotland, and Wales (Ellam et al. 1985); a subsample of the population were questioned in the same way but in addition their fitness was assessed by physiological measurements. This paper describes the characteristics of the physical fitness of an average fireman as revealed by responses to questionnaires and how firemen felt their fitness was related to their working duties; it further examines these in relation to objective measurements. PMID- 8206063 TI - Ergonomics in Northern Ireland: a survey of knowledge, attitudes, and implementation in industry and the public services. AB - In spite of the palpable benefits to organizations of applying the principles of ergonomics, it appears that a majority of employers, whether through ignorance or neglect, fail to do so (Simpson 1990). The present study sought to assess the impact of ergonomics on a broad cross-section of organizations in Northern Ireland from three perspectives: (1) knowledge and awareness of ergonomics; (2) attitudes towards ergonomics; and (3) the extent to which the principles of ergonomics were put into practice in the work-place. In all, 700 organizations were surveyed, representing manufacturing, service, and public sectors and ranging in size from 10 to more than 1000 employees. A total of 417 questionnaires (59.7%) were returned and, of these, 152 (36.5%) claimed no knowledge whatever of ergonomics. The extent to which knowledge was claimed tended to depend on the nature of the organizations. Analysis of the remaining 263 questionnaires revealed that, while only 36 organizations employed ergonomic specialists or engaged outside ergonomic consultants, 163 respondents reported specific instances of addressing ergonomic issues during the previous 12 months. Respondents exhibited generally positive attitudes towards ergonomics, although some cynicism was evident. Principal components analysis of the questionnaire items revealed several factors, most notably a general concern for ergonomic issues, cynicism towards ergonomics and, arguably, an attitude of helplessness concerning the state of the organization. Implications of these findings for promoting implementation of ergonomics within organizations are discussed. PMID- 8206064 TI - Antibiotic prophylaxis in Wertheim-Meigs surgery. A single dose vs three doses. AB - A prospective, randomized study to compare the prophylactic efficacy of a single dose of piperacillin with that of a three doses, was carried out with patients undergoing Wertheim-Meigs surgery. The results demonstrate that in this case three doses of piperacillin have a higher efficacy than one dose in the prevention of febrile complications and post-operative infections. PMID- 8206065 TI - Immunohistochemical expression of EGF-R in malignant surface epithelial ovarian neoplasms (SEON). AB - EGF-R expression was found to be increased in 40% of malignant epithelial ovarian neoplasms by an immunohistochemical method. No correlation was found between EGF R expression and clinical stage. There was a suggestion of reduced survival among tumours with positive EGF-R expression. PMID- 8206066 TI - Adenocarcinoma in a sigmoid neovagina 22 years after Wertheim-Meigs operation. Case report. AB - The development of carcinoma in the neovagina has rarely been reported. Depending on the type of tissue that has been used for the transplant, the tumor appears either as a squamous cell carcinoma or adenocarcinoma. It is important to draw a distinction not only between the patients with squamous cell carcinoma and adenocarcinoma, but also between those with neovagina performed due to congenital absence of the vagina and others in whom the procedure was performed because of an advanced cancer in the true pelvis. In the latter group of patients, it is generally difficult to distinguish a residual disease from a second primary of the same histology. There is no dilemma, however, when the histology differs as in the case presented. The patient reported here underwent surgery for squamous cell carcinoma of the cervix, stage Ib, in 1967. The intervention comprised a Wertheim-Meigs resection and sigmoid vaginoplasty. Considering the favourable histological findings, postoperative irradiation was not indicated. Following the procedure, the patient had been well and free of any major complaint for 22 years after surgery when she presented with a moderately differentiated adenocarcinoma of the neovagina. She was successfully operated upon and had no evidence of disease at the last follow-up examination, two and a half year after surgery. PMID- 8206067 TI - The value of estimating CA 125 in fluids from benign or malignant cysts, in the exudate and blood serum in women with ovarian cancer. AB - CA 125 levels were estimated by immunoenzymatic technique: in fluids obtained by puncturing benign ovarian cysts under guidance of USG and in the patients' sera (23 cases); in serum and in ascites of 39 ovarian cancer patients at the IIIrd or IV th stage of clinical advance; in the content of malignant tumors in the course of surgery (in 16 of the above listed patients). Ca 125 level was significantly lower in the content of benign Cysts as compared to malignant ones. CA 125 level higher than 1000/ml pointed to a malignant process. Both in serum and in ascites, more advanced tumors and tumors showing progression manifested higher levels of the marker than less advanced tumors and tumors characterized as stable disease. In the group of patients analysis of CA 125 levels provided less information on the disease course than in individual cases. PMID- 8206068 TI - Diagnostic value of the tumor markers in breast cancer. AB - The use of the most common tumor markers in breast cancer was reassessed in terms of cost effectiveness and the validity of their predictive information during the evaluation of the patients. Sera from 159 patients were studied. Acceptable diagnostic specificity was found only for CA 15-3. In predicting the presence of metastases the combination of CA 15-3 and CEA was observed to correlate with lymph node metastases. Introduction of MCA did not result in diagnostic improvement. Our results suggest that in practice a diagnostic panel for breast cancer can be confined to CA 15-3 and CEA. PMID- 8206069 TI - Primary squamous cell carcinoma of the endometrium. Case report and review of the literature. PMID- 8206070 TI - The absence of human papilloma virus (HPV) related parameters in sexually non active women. AB - In to order to investigate the prevalence of HPV related parameters in sexually non-active women, smears of 75 virgins were microscopically reviewed for alterations caused by HPV i.e. koilocytosis, parakeratosis and multinucleinization. In none of these smears were the mentioned parameters seen together, so the diagnosis of HPV infection could not be assessed. In an age matched control population consisting of 75 sexually active women smears were reviewed. In this group 10 smears (13%) were found positive for HPV infection, well in accordance with literature. PMID- 8206071 TI - Lymphocyte subpopulations in patients with cervical cancer. AB - The evaluation of the immunological aspects in cervical cancer has been a point of major interest in the past few years. Data found in literature are, however, often confusing. In order to identify changes in cell mediated immunoresponse in these malignancies, we have studied the lymphocyte subpopulations from peripheral blood samples in women with FIGO intraepithelial + IB stages vs a control group. The analysis of our results show evidence of an increase in the number of natural killer cells even in intraepithelial tumors. The activation of the immunological system from the very early stage is probably in response to viral antigens in the neoplastic cells and/or soluble factors produced by the tumor. PMID- 8206072 TI - Human papillomavirus infections of the genital region in human immunodeficiency virus seropositive women: integration of type 16 correlates with rapid progression. AB - The efficacy of treatment of HPV infections was evaluated in 14 HIV-1 seropositive women. Disease evolution was evaluated at follow-up examinations, and findings were compared to those in 14 historic HIV-negative women who had received similar treatment. HPV sequences were demonstrated by Southern blot in 13/14 HIV-positive women and by in situ hybridization in 5/13 HIV-negative women. Types 6/11, 16, and 31/33/35 were equally distributed in both groups; type 18 was never detected. In all but one case, the same viral type was present in different lesions, and in recurrences. Among the HIV-positive women, integration of viral sequences had occurred in the dysplastic lesions in 2 of the 3 HPV-16-positive cases; both cases showed progression to carcinoma in situ within 1 to 2 years. Despite comparable treatment, the HIV-positive women showed lesion persistence or progression, while all HIV-negative women experienced regression. PMID- 8206073 TI - Treatment of FIGO stage Ib cervical carcinoma with nodal involvement. AB - One hundred and eighty one patients with stage Ib cervical cancer underwent hysterectomy with pelvic lymphadenectomy. The overall incidence of lymph node metastases was 20%. Twenty seven (71%) patients with nodal involvement were treated by external radiotherapy (TCT) and 11 (29%) by both chemotherapy and radiotherapy (Lin. Acc.). The overall survival at 5 years was 80%; it was 43% for patients with positive nodes and 89% for patients without metastatic nodal disease. The 3 year survival of patients with positive nodes who underwent radiation therapy by TCT was 58%, while it was 72% for those treated by chemotherapy plus radiotherapy. We observed a recurrence in 23% of the cases, 52% in patients with positive nodes and 15% in those with negative nodes. The association chemo-radiotherapy in patients with metastatic lymph nodes seems to improve the survival and reduce the recurrence rate. PMID- 8206074 TI - Results of topical treatment of HPV infection in the uterine cervix using interferon beta, 13-cis-retinoic acid and TFX. AB - Local treatment was administrated to 130 women, in whom colposcopy, cytology and (if the latter was abnormal) histology pointed to HPV infection in uterine cervix. The best results were obtained with 13-cis-retinoic acid (provitamin A) in conjunction with interferon beta (94.2% cured patients), followed by interferon beta in combination with TFX (90% cured patients) and interferon beta administered alone (88% cured patients). PMID- 8206075 TI - Consolidation therapy in patients with advanced ovarian cancer. AB - Consolidation chemotherapy, to avoid relapses in Stage III or IV ovarian carcinoma is a major challenge in the management of ovarian carcinoma. The Author discusses, through a critical view of the more recent literature, the different approach to the problem. In particular he tries to answer the two principal questions regarding ovarian tumors: how to increase the number of patients with optimal response; how to consolidate the patients who achieve such a response. PMID- 8206076 TI - Vulvar intraepithelial neoplasia of low grade: a challenging diagnosis. AB - The authors reviewed 21 cases of "mild vulvar atypia" diagnosed from 1981 to 1990. The first 16 cases were diagnosed as hyperplastic dystrophy with mild atypia according to the 1976 ISSVD Classification of Vulvar Disease, while the last five cases were diagnosed as vulvar intraepithelial neoplasia grade I (VIN I). The review of the specimens was made by the same pathologist who gave the initial diagnosis and by a dermatopathologist unaware of the initial diagnosis. Both reviewers used the 1986 and 1989 ISSVD terminologies. The presence of "mild atypia" was confirmed in only four of the 21 specimens, that is in 19% of the cases, and two of them were found in the context of patients suffering from a lichen planus. These findings show that the diagnosis of mild atypia in vulvar tissues is a challenge and that mild vulvar atypia cannot be automatically considered a VIN I. PMID- 8206077 TI - Mitoxantrone in the treatment of recurrent ascites of pretreated ovarian carcinoma. AB - In this study we treated 19 patients with relapsed ovarian cancer with malignant peritoneal effusion. All patients were previously treated with cisplatin containing regimens. Intraperitoneal mitoxantrone was administered at a dosage of 20-30 mg/mq repeated every 28 days if ascites was still present. No patient was treated with systemic chemotherapy during the study. In 15 of 19 patients progressive ascites reduction was obtained. Moreover, in 4 of 15 responsive patients, a progressive reduction of the quantity of ascites was observed even though the abdominal masses demonstrated an increase in volume. Serum concentrations of Mitoxantrone (MXN) were determined, in ten patients, by high performance liquid chromatography with spectrophotometric detection, and low serum levels (1-30 ng/ml) with a maximum at the first or second hour were revealed. In conclusion, in patients with ovarian carcinoma and recurrent neoplastic ascites, palliative treatment with mitoxantrone was effective and well tolerated. The reduction of ascites and frequency of paracentesis represents a marked advantage for these patients and improves their quality of life. PMID- 8206078 TI - Role and evaluation of megakaryocytes and platelets in cardiovascular disease. A meeting perspective. PMID- 8206079 TI - Decreased clearance of uraemic and mildly carbamylated low-density lipoprotein. AB - Low-density lipoprotein (LDL) was in vitro carbamylated with potassium cyanate and the clearance was studied in man. A minor carbamylation of LDL decreased the clearance of LDL by 41% (94% of amino groups free) and by 18% (90% of amino groups free). When LDL was extensively carbamylated its clearance was substantially accelerated. Moreover, the clearance of LDL isolated from 14 haemodialysis patients (uremic-LDL) was studied in rabbits. Uraemic-LDL, injected into rabbits simultaneously with the LDL of a healthy control subject, was cleared more slowly than the control-LDL (difference in fractional catabolic rate -6.5%, P = 0.02). We also examined the lipid peroxidation of the carbamylated LDL by measuring the amount of thiobarbituric-acid reactive substances (TBARS) and formation of conjugated dienes during exposure of carbamylated LDL to 5 microM Cu2+. The carbamylated and native LDL had similar lipid peroxidation and propensity for oxidation. In summary, both the uraemic-LDL and minimally carbamylated LDL had a decreased clearance in vivo, which may contribute to the accelerated atherosclerosis in uraemic patients. PMID- 8206080 TI - The diagnosis of pulmonary tuberculosis by gaschromatographic detection of tuberculostearic acid using flame ionisation detectors. AB - It has been shown that the detection of tuberculostearic acid (TBSA) with gas chromatography-mass-spectrometry provides a highly specific, sensitive and rapid method for the diagnosis of various forms of tuberculosis. However, the need for complex and expensive equipment prevented the more widespread use of this method. We report on the application of conventional gas chromatography with flame ionization detectors in the detection of TBSA in sputum samples. TBSA was detected in all patients with proven pulmonary tuberculosis before treatment or under treatment for less than 4 weeks (n = 18). Six of these patients (33%) had a negative microscopy result at the time of the study. Sputum samples from patients under therapy for longer than 4 weeks (n = 20) were TBSA-positive in 15 cases (75%). Only in two cases was the diagnosis by microscopy and/or culture not met by TBSA-detection. All sputa of 20 control patients with lung diseases other than tuberculosis were TBSA negative. Additional analysis of patients' data showed a significant relationship (P < 0.005) between the relative amounts of TBSA detectable in the sputum samples and the duration of therapy. It is concluded that conventional capillary gaschromatography may be sensitive and specific enough to be used for the detection of TBSA in sputum of patients with pulmonary tuberculosis. PMID- 8206081 TI - T-cell receptor gene rearrangements in lymphoid and non-lymphoid leukaemias. AB - Rearrangements of delta-, tau-, and beta- T-cell receptor (TcR) chain genes were analysed in 64 haematologic malignancies comprising T- and B-lineage acute lymphoblastic leukaemias (ALL), B-chronic lymphocytic leukaemias (CLL), acute myeloid leukaemias (AML) and acute undifferentiated leukaemias AUL). The TcR genes were rearranged in 5/6 T-ALL. In non-T-leukaemias the frequency of TcR gene rearrangements was higher in B-lineage ALL (8/11), although they were all detected in B-CLL (5/29), AML (1/16) and AUL (2/4). Immunoglobulin (Ig) gene rearrangements were observed in 1/6 T-ALL and 2/14 AML. The analysis of these gene configurations has a diagnostic application since it allows the definition of the clonality of malignant proliferation and although they are not lineage specific such configurations represent a further parameter to evaluate, together with the immunophenotype and morphology, in the assignment or exclusion of the differentiation lineage of the haematologic malignancies. PMID- 8206082 TI - Plasma fibrinogen in relation to serum insulin, smoking habits and adipose tissue fatty acids in healthy men. AB - Recent prospective studies have reported an independent association between fibrinogen plasma levels and risk of cardiovascular events. Aim of this study was to investigate the relationships between fibrinogen level and conventional cardiovascular risk factors in a random sample of 38 year-old apparently healthy men (n = 94), and to verify whether the fatty acid composition of the diet might influence those relations. Anthropometric measurements, serum lipids, blood pressure, and smoking habits were evaluated. In addition, fasting and after glucose-load serum glucose and insulin concentrations were measured. The most significant difference in fibrinogen level was found among the tertiles of fasting serum insulin (F-ANOVA = 4.5; P < 0.01) with the highest plasma fibrinogen values in the third insulin tertile, whereas body mass index (BMI), waist/hip circumference ratio (WHR) and serum triglycerides were more weakly related. The current smokers had substantially higher levels of fibrinogen than subjects who never smoked (P < 0.001). A multivariate regression analysis showed that, among the above reported variables, only serum insulin and smoking were independently associated with plasma fibrinogen. Furthermore, as the possible association between fatty acid composition of the diet and fibrinogen level regards, we have examined the fatty acid composition of adipose tissue, as a good and objective index of quality of the dietary fat intake. It was found that, fibrinogen level was not associated with any adipose tissue fatty acid. In conclusion, this study performed in a random sample of healthy men indicates an independent relationship of fasting insulin and smoking to fibrinogen plasma level. PMID- 8206083 TI - Regulation of VLDL secretion in primary culture of rat hepatocytes: involvement of cAMP and cAMP-dependent protein kinases. AB - When hepatocytes were cultured for 24 h in the presence of forskolin (10(-4) mol l-1) or isobutylmethylxanthine (IBMX, 10(-3) mol l-1), the intracellular cAMP concentration peaked (320-380 pmol mg-1 protein) after 10-20 min of culture. This increase was accompanied by a decrease in the secretion of triacylglycerol, cholesterol and apoprotein B associated with VLDL. After 4 h cAMP levels had returned almost to basal values but the inhibition of VLDL secretion persisted. There was a small intracellular accumulation of triacylglycerol but not of apoprotein B. Addition of forskolin and IBMX together led to a further increase in intracellular cAMP and a further suppression of VLDL output. Similar effects on the secretion of VLDL were also observed after addition of Bt2cAMP. Exposure of cell cultures to glucagon (10(-7) mol l-1) for only 10 min raised cellular cAMP levels to > 200 pmol mg-1 protein, and suppressed VLDL secretion during the next 24 h to < 40% of control. All of the substances tested inhibited de novo synthesis of fatty acids but had little or no effect on cholesterol synthesis and did not inhibit oleate esterification to triacylglycerol. The cAMP-dependent protein kinase antagonist Rp-cAMPS prevented suppression of VLDL triacylglycerol secretion induced by glucagon (10(-7) mol l-1) and abolished glucagon-induced ketogenesis. Rp-cAMPS also inhibited Bt2cAMP (7.5 x 10(-6) mol l-1)-induced suppression of VLDL secretion and enhancement of ketogenesis. It is concluded that rat hepatic VLDL metabolism can be regulated by cAMP and cAMP-dependent protein kinases, and that the initial transient rise in cellular cAMP levels induced by glucagon is sufficient to maintain a long-term inhibitory effect on assembly and secretion of VLDL. PMID- 8206084 TI - Neurobiological aspects of the chronic fatigue syndrome. PMID- 8206085 TI - 28th Annual meeting of the European Society for Clinical Investigation. Toledo, Spain, April 20-23, 1994. PMID- 8206086 TI - Effect of CTLA-4 chimeric protein on rat autoimmune anti-glomerular basement membrane glomerulonephritis. AB - The interaction of the T cell receptor with the antigen/major histocompatibility class II complex is insufficient to induce optimal T cell activation. Co stimulatory signals, including those provided by CD28/CTLA-4 on T cells and B7 molecules (B7-1, -2, and -3) on antigen-presenting cells, are also required. CD28 B7 interactions can be blocked by a soluble human CTLA-4 chimeric protein (CTLA4Ig). We tested the effect of administration of CTLA4Ig on experimental anti glomerular basement membrane (GBM) autoimmune glomerulonephritis in Wistar-Kyoto rats induced by immunization with bovine GBM. The disease is characterized by development of antibody to the alpha 3 chain of type IV collagen (Goodpasture's antigen), deposition of rat IgG in GBM, infiltration of the kidney by T cells and macrophages, severe crescent formation and renal failure leading to death in 5-6 weeks. Animals injected with human CTLA4Ig from day 0 to day 14 or to day 35 had reduced disease severity. Beneficial effects were observed even when injections were begun after the onset of glomerulonephritis on day 14. However, the rats developed antibody to the human CTLA4Ig, associated with reduction in levels of circulating CTLA4Ig. The results provide evidence for CD28/CTLA-4 signaling in rat autoimmune glomerulonephritis, and suggest that more effective inhibition of B7-dependent T cell activation, such as might be achieved with homologous CTLA4Ig, could be useful in the treatment of autoimmune diseases. PMID- 8206087 TI - Comparing macrophages and dendritic leukocytes as antigen-presenting cells for humoral responses in vivo by antigen targeting. AB - Immunotargeting is a novel technique whereby antigen is directed against antigen presenting cells (APC) by conjugation to specific monoclonal antibodies (mAb). In this study we have employed the technique to investigate the efficiency of macrophages as APC compared with constitutively major histocompatibility complex (MHC) class II-positive cells, i.e. dendritic leukocytes and B cells, in vivo. We first studied the organ retention of the radiolabeled conjugates by gamma counting, and their distribution within the draining lymph nodes by autoradiography. We could confirm that the conjugates reached the cells at which they were aimed. We then measured primary and secondary humoral responses. The results confirmed previous findings that targeting with mAb against MHC class II, i.e. to dendritic leukocytes, strongly enhanced the primary humoral response. In contrast, anti-IgD conjugates, directed against B cells gave only weak primary responses. Although conjugates directed against macrophages were retained for a longer time than the other conjugates, the primary humoral response was virtually abolished. The secondary responses, however, were at least as strong as those obtained in animals primed with control conjugates, whereas animals primed with anti-MHC class II conjugates showed little if any amplification of the secondary response. The discrepancies between the various conjugates could not be ascribed to TH1 versus TH2 responses as IgG1, IgG2a, IgG2b and IgE titers all co-varied in single animals. A possible explanation for the observed results is that macrophages fail to induce cytokine production for terminal differentiation of B cells to plasma cells, whereas conversely, upon presentation by dendritic leukocytes most stimulated B cells mature to plasma cells, leaving less progeny for immunological memory. PMID- 8206088 TI - Exogenous peptide ligand influences the expression and half-life of free HLA class I heavy chains ubiquitously detected at the cell surface. AB - A pool of free HLA class I chains has been detected at the plasma membrane of all cells concomitantly expressing folded and assembled class I molecules. To determine the origin of these free HLA heavy chains, we have examined the biosynthesis of a single HLA class I molecule, HLA-B27, expressed by a murine cell line (L-B27). In L-B27 cells, as previously shown in Epstein-Barr virus transformed lymphoblastoid cell lines, a precursor/product relationship exists, early in biosynthesis, between free (HC10-reactive) and beta-2-microglobulin (beta 2m)-associated (W6/32-reactive) class I heavy chains as demonstrated by pulse/chase experiments. At later stages in class I biosynthesis, both HC10- and W6/32-reactive heavy chains display complex oligosaccharides and accumulate at the cell surface. HC10- and W6/32-reactive molecules are both very stable at the cell surface, with half-lifes (t1/2) of > 7 h and approximately 4 h, respectively. Interestingly, cell surface expression and turnover of HC10- and W6/32-reactive molecules were affected by the addition of peptide ligands to the culture media. Culturing cells in the presence of HLA-B27 ligands resulted in the increased expression of W6/32-reactive molecules and the decreased expression of HC10-reactive molecules. Moreover, addition of exogenous peptide extended the t1/2 of W6/32-reactive molecules to > 7 h and reduced that of HC10-reactive molecules to 4 h. These results indicate that surface HC10-reactive molecules result largely from W6/32-reactive molecules following peptide and beta 2m dissociation. Therefore, HC10-reactive species are not only the precursors but also the end products in class I biosynthesis. PMID- 8206089 TI - Transforming growth factor-beta 2 induces apoptosis of murine T cell clones without down-regulating bcl-2 mRNA expression. AB - Transforming growth factor-beta (TGF beta) is a potent immunosuppressive cytokine which inhibits the antigen (Ag)-dependent expansion of T cells both in vitro and in vivo by mechanisms not well defined yet. Here we report that exposure of interleukin (IL)-2-dependent T cell lines to TGF beta 2 results in apoptosis defined by morphology, nucleosomal size DNA fragmentation and in situ DNA end labeling. TGF beta 2-induced T cell apoptosis showed the following characteristics: (1) in contrast to the rapid evolution of apoptosis following IL 2 deprivation, apoptosis of T cells triggered by TGF beta 2 was delayed; (2) cycloheximide prevented TGF beta 2-induced apoptosis of CTLL-2 but not of OVA-7 T helper cells; (3) in contrast to apoptosis following IL-2 deprivation, TGF beta 2 mediated T cell apoptosis was not associated with decreased expression of the proto-oncogenes, bcl-2 or c-myc; (4) TGF beta 2-induced apoptosis was not restricted to IL-2-dependent T cell lines since the IL-4-dependent T cell line, CT.4S, as well as EL4 lymphoma cells, which grow independently of exogenous IL-2, were also susceptible to TGF beta 2-mediated apoptosis. Taken together, these data may present a novel mechanism of TGF beta 2-mediated suppression of T cell expansion in response to Ag and IL-2, the activation of the endogenous death program of apoptosis, which appears to operate independently of direct interactions of TGF beta 2 with the IL-2/IL-2 receptor system. PMID- 8206090 TI - Cytokine synthesis and apoptosis by intestinal intraepithelial lymphocytes: signaling of high density alpha beta T cell receptor+ and gamma delta T cell receptor+ T cells via T cell receptor-CD3 complex results in interferon-gamma and interleukin-5 production, while low density T cells undergo DNA fragmentation. AB - To study the biological consequences of cytokine production and apoptosis by intraepithelial lymphocytes (IEL), we have studied these characteristics in both the high and low density CD3+ IEL populations. Stimulation of low- or high density CD3+ IEL via the T cell receptor (TCR)-CD3 complex using monoclonal anti CD3, anti-alpha beta TCR or anti-gamma delta TCR antibodies resulted in opposing effects. In one case, a significant number of the high-density CD3+ T cells entered cell cycle from the resting stage (DNA replication was observed) and anti TCR-CD3 treatment enhanced the numbers of interferon-gamma and interleukin-5 spot forming cells in this cell fraction. In contrast, when the low-density alpha beta TCR+ or gamma delta TCR+ T cells were activated via the TCR-CD3 complex, DNA fragmentation was observed. These results demonstrated that the activation signals transduced via the TCR-CD3 complex resulted in their entry into the cell cycle and subsequent interferon-gamma and interleukin-5 production in the high density IEL T cell subset. However, identical signals induced apoptosis in the majority of the low-density fraction of CD3+ IEL. PMID- 8206091 TI - In vivo and in vitro IgE isotype switching in human B lymphocytes: evidence for a predominantly direct IgM to IgE class switch program. AB - Molecular analysis of circular excision products and composite genomic switch regions has demonstrated that in mice, immunoglobulin (Ig) isotype switching from IgM to IgE often proceeds sequentially via IgG1. Based on analysis of Ig production in cell cultures, it has been suggested that human B cells may switch to IgE via IgG4, whereas limited molecular data from in vitro switched B cells suggest a direct IgM to IgE switch program. To obtain a quantitative assessment of direct versus sequential IgE switching in humans, we have analyzed the nucleotide sequences of 29 composite S mu/S epsilon switch regions from freshly isolated human B lymphocytes from patients with atopic dermatitis and from B lymphocytes induced to switch to IgE synthesis in vitro. The data show that in these B cells IgE isotype switching progressed directly from IgM to IgE. We conclude that, in contrast to the murine IgM/IgE switch program, the IgM to IgE switch in B lymphocytes from patients with atopic dermatitis as well as in vitro stimulated B cells from healthy donors preferentially proceeds via direct S mu to S epsilon switch recombination. PMID- 8206092 TI - Multiple natural killer cell-activating signals are inhibited by major histocompatibility complex class I expression in target cells. AB - Several lines of evidence indicate that major histocompatibility complex class I molecules expressed by target cells can prevent natural killer cell (NK) lysis, possibly by engaging inhibitory receptors expressed by NK cells. On the other hand it is likely that NK cells must be activated to lysis by the recognition of unidentified NK target structures on target cells. To investigate the relationship between positive activation of NK cells by NK target structures versus inhibition by target cell class I molecules, we have examined various NK/target cell interactions for which the expression of inhibitory class I molecules by the target cells is known. The results suggests that specific properties of the target cell other than the absence of class I expression are necessary to activate NK-mediated lysis. Furthermore, different effector cell populations, i.e. freshly isolated versus interleukin-2 activated NK cells, differ in their capacity to kill class I-deficient lymphoblast target cells. In general, class I-deficient target cells that are resistant to direct lysis by a given NK population can be lysed by the NK cells when the reaction is mediated by antibody-dependent cellular cytotoxicity (ADCC). Most significantly, all types of NK-mediated lysis of lymphoblasts, of tumor cells and of almost any target by ADCC can be inhibited by appropriate class I gene expression in the target cell. These results suggest a model in which lysis by NK cells must be triggered by any one of a set of distinct target cell ligands, but that all of these signals can be overruled by class I-mediated inhibition. PMID- 8206093 TI - The anti-La response of a single MRL/Mp-lpr/lpr mouse: specificity for DNA and VH gene usage. AB - Autoantibodies to ribonucleoproteins (RNP) occur prominently in human systemic lupus erythematosus and murine lupus models. In previous studies we demonstrated a relationship in MRL/Mp-lpr/lpr (MRL/lpr) mice between antibodies to Sm, an RNP autoantigen, and antibodies to DNA. Thus, many anti-Sm monoclonals bound DNA and expressed the same V region genes as anti-DNA. In addition, many had multiple VHCDR3 Arg residues suggestive of selection by DNA, and some had somatic mutations suggesting selection for mutant B cells by DNA. To determine whether autoantibodies to other RNP antigens are also associated with the anti-DNA response, we have analyzed the response to the La RNP. Six anti-La B cell hybridomas were generated from a single MRL/lpr mouse. Southern blot analysis of Ig V gene rearrangements and V gene sequences indicated two clonally related pairs, suggesting an oligoclonal response. Antibodies from all six hybridomas bound single-stranded DNA, while antibodies from five hybridomas bound double stranded DNA. Two hybridomas expressed a VH7183 gene which is used by members of two previously reported anti-DNA clones and two anti-Sm/DNA clones of MRL/lpr origin. These data demonstrate an association between the anti-La and anti-DNA responses in MRL/lpr mice, suggesting that cross-reactive anti-RNP and anti-DNA responses are a general feature of autoimmunity in this lupus model. PMID- 8206094 TI - Negative selection of multireactive B cell clones in normal adult mice. AB - In the absence of intentional immunizations, normal mice produce natural antibodies that react with a variety of self and foreign antigens. We have now addressed the putative physiological selection of such reactivities and some of their clonal characteristics, by analyzing antibodies produced by B cells at different stages of differentiation. Using an antigen-specific spot-enzyme-linked immunosorbent assay (ELISA) with a panel of self and foreign antigens, we found that newly formed B cells, either from adult bone marrow or from newborn spleen, contain the highest frequencies of IgM antibodies with reactivities towards the panel. Resting peripheral B cells show lower frequencies of such antibodies, that are lowest among naturally activated splenic plasma cells. Analyses of monoclonal IgM antibodies derived from lipopolysaccharide-stimulated bone marrow and spleen cell hybridomas in normal mice show that the majority of reactivities scored in spot-ELISA originate from multireactive IgM clones. In Western blots against a large number of self antigens, each multireactive IgM antibody studied shows a unique and specific pattern of reactivity. We conclude that multireactive B cell clones are very frequent in the emergent repertoires of newborns and adults, but are subsequently negatively selected from bone marrow to periphery, and from the available repertoire to that of natural plasma cells. It, thus, seems that multireactivity of natural antibodies is not a positively selected property, but represents the sum of unique multireactive clones that have escaped inactivation or deletion. PMID- 8206095 TI - Regulation of VH-gene expression is a lineage-specific developmental marker. AB - We have previously shown that in IgH congenic mice VH-gene family usage in neonatal spleen B cells and adult Ig-secreting cells is entirely determined by the IgH locus, while in adult resting B cells it is regulated by genetic element(s) located outside the IgH locus. Two observations reported here demonstrate that the differential expression of VH genes is an intrinsic property of the respective cell populations, determined by both the IgH locus and by a cis element(s) operating independently in the same animal. First, the study of F1 hybrids between the IgH congenic B6a and CB.20 strains demonstrates that cis elements control VH-gene family expression. Second, studies in irradiation chimeras showed that the environment in which cell differentiation proceeds is unable to overcome those controls. In chimeras of IgH congenic donors, VH-gene expression in fetal liver-derived splenic B cells and Ig-secreting cells is dictated by the IgH haplotype, while in bone marrow-derived B cells is entirely determined by the cis element(s). These results show a developmental and cell lineage-related restriction in VH-gene expression, and suggest that most adult splenic Ig-secreting cells may originate from precursors originally present in fetal liver, but which are rare among adult bone marrow precursors and CD5+ B cells. PMID- 8206096 TI - Intracellular Ca2+ stores of T lymphocytes: changes induced by in vitro and in vivo activation. AB - Intracellular Ca2+ stores were investigated in resting and activated splenic T lymphocytes from Lewis rats. Activation was obtained either in vitro (spleen cells isolated from "naive" rats exposed to concanavalin A for 24 h) or in vivo (spleen cells from rats with fully developed symptoms of experimental allergic encephalomyelitis). In both experimental conditions several changes of Ca2+ homeostasis were observed with respect to resting lymphocytes: (1) a threefold increase of the total intracellular calcium (from 1.15 to 3.5 mmol/l); (2) a moderate increase of the pool sensitive to inositol 1,4,5-trisphosphate (IP3), investigated both in intact T lymphocytes (fura-2 and 45Ca(2+)-release techniques in cells challenged with phytohemagglutinin) and in T lymphocytes permeabilized with beta-escin (45Ca2+ release induced by saturating concentrations of IP3); and (3) the appearance of a pool released by the endoplasmic reticulum (ER) Ca2+ ATPase inhibitor thapsigargin (Tg), but insensitive to IP3, which, therefore, appears to be localized in areas of the ER devoid of the cognate receptor. The latter two findings were paralleled in activated lymphocytes by an increase of expression of ER markers, involved (calreticulin; Ca2+ ATPase) or not (protein disulfide isomerase) in the regulation of Ca2+ homeostasis. In contrast, calnexin (another ER marker) and the receptor for IP3 were increased to only a moderate extent. Finally, an enlargement of non-ER Ca2+ pools was observed in the cells pretreated with Tg in which 45Ca2+ release was induced by the Ca2+ ionophore ionomycin. Our results document structural and functional changes of intracellular Ca2+ stores which might play an important regulatory role in activated T lymphocytes. PMID- 8206097 TI - Soluble transferrin mediates targeting of hepatitis B envelope antigen to transferrin receptor and its presentation by activated T cells. AB - In a previous study, we identified that transferrin receptor (TfR) is the receptor utilized by hepatitis B virus (HBV) to enter T cells. We demonstrated that hepatitis B envelope antigen (HBenvAg) is taken up by activated T cells via TfR, processed in endosomal compartments, and presented on class II molecules to specific CD4+ T cell clones. Herein, we report that binding to soluble ferric Tf by HBenvAg is needed in TfR-mediated endocytosis. Accordingly, presentation of HBenvAg by activated T cells is not observed in serum-free medium and is restored by addition of soluble Tf. Moreover, we provide evidence that pre-S2 and S regions of HBenvAg contain the critical residues for the interaction with soluble Tf. Our data not only explain HBV entry into a variety of host activated cells, but may also help in developing strategies to alter the course of chronic HBV infection. PMID- 8206098 TI - B lymphocyte and macrophage expression of carcinoembryonic antigen-related adhesion molecules that serve as receptors for murine coronavirus. AB - The expression of carcinoembryonic antigen (CEA)-related glycoproteins that have been associated with intercellular adhesion and that serve as receptors for mouse hepatitis virus (MHV) was analyzed in cells from the immune system of BALB/c mice using immunolabeling and RNA polymerase chain reaction amplification of receptor transcripts. These glycoproteins, which are called biliary glycoproteins, were highly expressed in B lymphocytes, including cells of the B-1a (CD5+) lineage, and in macrophages, but were not detectable in resting T lymphocytes. Similarly, murine cell lines of B cell and macrophage origin expressed messenger RNA encoding CEA-related molecules, while the corresponding mRNA was only slightly detectable in a T cell line. These CEA-related cell adhesion glycoproteins were also expressed in endothelial cells. Therefore, their specific interaction with their so far unknown ligand may be of functional importance in cellular interactions in the immune response. Monoclonal antibody directed against these glycoproteins blocked MHV-A59 infection of the B cell-derived SP20 cell line. Thus, the functional receptors for MHV on B lymphocytes, like those on murine fibroblasts, are isoforms of CEA-related glycoproteins. Treatment of B cells with anti-receptor antibody also blocked B cell-mediated cytotoxicity against MHV-A59 infected fibroblasts, indicating that this phenomenon is mediated by interaction of viral attachment protein on the infected target cells with specific CEA related receptor glycoproteins on the effector B cells. PMID- 8206099 TI - Human CD45RA+ and CD45R0+ T cells exhibit similar CD3/T cell receptor-mediated transmembrane signaling capacities but differ in response to co-stimulatory signals. AB - CD45RA+ cells have been described to be less responsive to CD3/T cell receptor (TcR)-mediated activation than CD45R0+ T cells. To analyze the underlying mechanism of the differential responses we compared CD3/TcR-triggered tyrosine phosphorylation in the two subsets and studied the role of co-stimulatory signals provided either by accessory cells or pharmacologic activation of protein kinase C by phorbol ester. Stimulation of purified CD45RA+ and CD45R0+ T cells with CD3/TcR antibodies induced similar patterns and intensities of tyrosine phosphorylation in the two subsets, but no proliferation. If accessory cells were used as the source of co-stimulatory signals, strong expression of the 55-kDa chain of the interleukin-2 (IL-2) receptor (CD25), significant IL-2 production and vigorous proliferation were observed in CD45R0+ cells, whereas CD45RA+ cells responded weakly. However, when CD3/TcR-mediated triggering was combined with activation of protein kinase C by phorbol ester, CD45RA+ cells responded strongly. These data indicate that the transmembrane signaling capacity of the T cell receptor expressed by CD45RA+ and CD45R0+ cells is similar and, therefore, is presumably not responsible for the differential reactivities of the two subsets. It is more likely that co-stimulatory signals determine whether CD3/TcR initiated activation results in strong or weak responses. PMID- 8206100 TI - Suppression of polyclonal and antigen-specific murine IgG1 but not IgE responses by neutralizing interleukin-6 in vivo. AB - The crucial role of interleukin (IL)-4 in the induction of murine IgG1 and IgE responses, which are coupled through the process of sequential isotype switching, has been well documented. Whereas IL-4 is obligatory for the induction of IgE responses, it enhances IgG1 responses. In this study, using neutralizing antibodies, we provide evidence that, besides IL-4, also IL-6 is required for obtaining peak IgG1 responses. The mRNA levels of these two cytokines are coordinately expressed in the spleen of mice immunized with trinitrophenol keyhole limpet hemocyanin (TNP-KLH). No IL-6 requirement was observed for peak IgE responses. The IL-6 dependence of IgG1 responses was found for both antigen specific and polyclonal responses. Moreover, it was noted using TNP-KLH and goat anti-mouse (GAM) IgD as antigen that polyclonal IgG1 responses are more dependent on IL-6 than antigen-specific responses. In vitro experiments revealed that exogenous IL-6 neither enhanced nor inhibited the IgG1 and IgE production by naive B cells, suggesting that IL-6 did not interfere with the IL-4-induced isotype switch potential. Primary and memory IgG1 responses were both similarly dependent on IL-6. These observations point to a role of IL-6 in the terminal differentiation of B cells switched to IgG1. Neutralization of IL-6 did not inhibit either antigen-specific or polyclonal IgE responses. Therefore, it was concluded that IL-6 is not involved in the terminal differentiation of B cells switched to IgE. These findings thus provide a distinct role for IL-6, besides IL 4, in regulating murine IgG1 responses. The formation of IgE, however, is completely dependent on IL-4 alone. PMID- 8206101 TI - Preformed purified peptide/major histocompatibility class I complexes are potent stimulators of class I-restricted T cell hybridomas. AB - A panel of antigen-specific, major histocompatibility complex class I-restricted T cell hybridomas has been generated to examine the capacity of peptide/class I complexes to stimulate T cells at the molecular level. Peptide/class I complexes were generated in detergent solution, purified and quantitated. Latex particles were subsequently coated with known amounts of preformed complexes and used to stimulate the T cell hybridomas. Stimulation was specific, i.e. only the appropriate peptide/class I combination were stimulatory, and quite sensitive, i.e. as little as 300 complexes per bead could be detected by the T cells. Preformed complexes were about 500,000 times more potent than free peptide in terms of T cell stimulation, demonstrating the physiological relevancy of the biochemically generated complexes. Surprisingly, the majority (including the most sensitive of the hybridomas) had lost CD8 expression, suggesting that antigen specific stimulation of class I-restricted T cell hybridomas, as assessed by IL-2 release, does not depend on CD8. PMID- 8206102 TI - Induction of anergy in resting human T lymphocytes by immobilized anti-CD3 antibodies. AB - How the T cell receptor (TcR)/CD3 complex mediates not only the induction of T cell activation but also suppressive effects like T cell anergy or apoptosis is not well understood. Here we describe a series of preincubation and restimulation experiments which demonstrate that primary stimulation of resting, unseparated human T cells with mitogenic doses of immobilized anti-CD3 antibodies induces hyporesponsiveness upon restimulation of the cells. Various costimuli can prevent this type of anergy to a variable degree if present during the preincubation period, phorbol 12-myristate 13-acetate (PMA) being the most and anti-CD4 antibody the least effective. If employed together with anti-CD3 antibody during the restimulation phase of the assay, interleukin (IL)-2, IL-4 and anti-CD28 antibody break anergy almost completely. Proliferation induced by a submitogenic dose of anti-CD3 antibody supplemented by costimulatory signals (anti-CD2, anti CD4, anti-CD28, IL-2, IL-4 or PMA) does not result in hyporesponsiveness. Taken together, these results support a modified view of the two-signal model for T cell activation according to which anergy induction in resting T cells occurs if primary proliferation is induced by high density triggering of the TcR/CD3 complex in the absence of accessory signals. We discuss possible implications of these findings for the induction of peripheral tolerance. PMID- 8206103 TI - Use of a skin test assay to determine tumor-specific CD8+ T cell reactivity. AB - We have observed delayed-type hypersensitivity (DTH) reactions in immunized mice challenged subcutaneously with class I-binding peptides related to rejection antigens recognized by cytotoxic T lymphocytes on mutagenized (tum-) variants of mastocytoma P815. As observed by skin test in virally infected mice challenged with viral peptides, the intrafootpad injection of tum- peptides resulted in a dose-dependent DTH that peaked at approximately 24 h. The response was mediated by CD8+ cells and could be induced by previous vaccination of mice with live tumor cells, intrasplenic deposition of the eliciting peptide, or adoptive transfer with peptide-pulsed syngeneic dendritic cells. These sensitization procedures resulted in an immunologically specific footpad reaction detectable for up to 2-6 months after priming. The evaluation by DTH in cancer patients of long-lived CD8+ anti-tumor T cell responses following local challenge with tumor specific peptides may be of great interest in human immunotherapy trials involving immunization against identified tumor antigens. PMID- 8206104 TI - The 5' boundary of somatic hypermutation in a V kappa gene is in the leader intron. AB - The maturation of the immune response involves the hypermutation of antibody genes and the selection of B cells expressing receptors with improved antigen binding properties. Somatic hypermutation of antibody genes is targeted to a small region approximately 1 kb surrounding the rearranged V gene. The precise definition of the 5' limit is not yet clear since the data base of somatic mutations upstream of the V region is very restricted. The available data suggest that it lies close to the promoter region and this has been used to implicate transcription in the mechanism leading to hypermutation. Here we present an extensive analysis of mutations in the 5' region of a single kappa light chain gene. A large data base from highly mutated sequences was obtained from anti oxazolone hybridomas expressing the V kappa Ox1-J kappa 5 light chain and from polymerase chain reaction-derived clones from splenic and Peyer's patches of transgenic mice expressing the same V kappa Ox1-J kappa 5 gene combination. Although mutations were found in the 5'-flanking segment, the rate of mutation in the V-J segment was about 20-fold higher. A sharp decline between those two mutation rates is evident but the boundary was found in the leader intron of the V kappa Ox1 gene, about 150 bases downstream of the initiation of transcription site. PMID- 8206105 TI - Epstein-Barr virus (EBV) latent membrane protein 1 increases HLA class II expression in an EBV-negative B cell line. AB - Transformation of normal resting B cells by the Epstein-Barr virus (EBV) leads to the establishment of permanent lymphoblastoid cell lines (LCL) which express high levels of HLA antigens and which are highly efficient in antigen presentation. Certain features of the LCL phenotype can be reproduced by transfecting EBV negative B lymphoma (BL) cell lines with individual EBV latent genes under heterologous promoters. In this work we have analyzed a series of subclones derived from the EBV-negative cell line Louckes, stably transfected with constructs encoding EBV latent genes for their expression of HLA class II molecules. Louckes parental cells and control transfectants expressed detectable levels of HLA-DR, DQ and DP antigens on the cellular surface by cytofluorometry, but these levels were significantly increased in transfectants expressing the virus-coded latent membrane protein 1 (LMP-1). Northern blotting for the individual alpha and beta chain mRNA at each of the three HLA class II loci indicated correspondingly increased levels of HLA class II transcripts in the LMP 1 transfectants. Transfectants expressing the virus-coded nuclear antigens EBNA 1, EBNA-2 or EBNA-LP showed no significant changes in these parameters. These observations indicate that up-regulation of HLA-class II molecules can be a part of the changes induced by LMP-1 in B cells. PMID- 8206106 TI - Cyclosporine effect on ornithine decarboxylase activity in rat submaxillary lymph nodes. Modulation by parasympathetic nerves. AB - This study was performed: (1) to assess whether cyclosporine affected the increase in submaxillary lymph node ornithine decarboxylase activity induced by complete Freund's adjuvant injection to rats bearing a regional parasympathetic decentralization; (2) to examine the effect of cyclosporine on cholinergic markers in submaxillary lymph nodes of rats injected with complete Freund's adjuvant or its vehicle. The unilateral parasympathetic decentralization of the submaxillary lymph nodes was achieved by unilateral chorda tympani section; each rat was also contralaterally sham-operated. A 73% decrease of choline acetyltransferase activity and a 78% decrease of neuronal [3H]choline uptake, were found in the ipsilateral side 2 weeks after surgery. Cyclosporine (5 or 20 mg/kg) or its vehicle was s.c. injected once daily for 5 days. Freund's complete adjuvant or its vehicle was injected s.c. 1 h before the 3rd injection of cyclosporine. The animals were killed 2 h after the last cyclosporine injection. Parasympathetic decentralization of the submaxillary lymph nodes was followed, 2 weeks later, by a significant inhibition of cyclosporine activity on Freund's adjuvant-induced ornithine decarboxylase. In rats injected with complete Freund's adjuvant or its vehicle, sympathetic denervation of submaxillary lymph nodes achieved by unilateral superior cervical ganglionectomy, augmented the stimulatory activity of cyclosporine on choline acetyltransferase and neuronal choline uptake. Cyclosporine treatment did not modify the total [3H]choline uptake, regardless of Freund's adjuvant injection or of intactness of the sympathetic innervation. Choline acetyltransferase and choline uptake were significantly augmented by the injection of Freund's adjuvant alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206107 TI - Antinociceptive effect of L-arginine in diabetic mice. AB - The antinociceptive effect of L-arginine in streptozotocin-induced diabetic mice was examined. Although s.c. administration of L-arginine produced a dose dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice, the antinociceptive response was greater in diabetic mice than in non diabetic mice. The antinociceptive effects of L-arginine in both diabetic and non diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective delta-opioid receptor antagonist. However, neither beta funaltrexamine, a selective mu-opioid receptor antagonist, nor nor-binaltorphimin ++, a selective kappa-opioid receptor antagonist, significantly affected the antinociceptive effect of L-arginine in diabetic and non-diabetic mice. These results suggest that L-arginine produces a marked antinociceptive effect in diabetic mice through the activation of delta-opioid receptors. PMID- 8206108 TI - Selective reduction in dopamine turnover in the rat frontal cortex and hypothalamus during withdrawal from repeated cocaine exposure. AB - The effects of 7 days repeated cocaine administration on the dynamics of dopamine release and metabolism in four rat brain regions (frontal cortex, hypothalamus, nucleus accumbens and striatum) were evaluated 1 week (long-term effects) after the final cocaine injection. 3-Methoxytyramine and 3,4-dihydroxyphenylacetic acid (DOPAC) rates of formation were respectively used to assess the dynamics of dopamine release and metabolism. Consistent with a previous report, cocaine withdrawal was associated with marked reductions in DOPAC rate of formation in the frontal cortex and hypothalamus but not in the nucleus accumbens or the striatum. Dopamine release as indicated by 3-methoxytyramine steady-state concentration and its rate of formation was normal in all four brain regions 1 week after repeated cocaine exposure. The ratios of 3-methoxytyramine rate of formation to that of DOPAC were calculated and found to be increased in the frontal cortex and hypothalamus suggesting dopamine reuptake inhibition, at least 1 week after cocaine withdrawal, continued to be depressed in these regions. It is concluded that repeated cocaine has no long-term effect on dopamine release but produces selective long-term reductions in dopamine turnover in frontal cortex and hypothalamus. Cocaine withdrawal is therefore better associated with changes in dopamine turnover than with its release. PMID- 8206109 TI - Effects of the selective 5-HT1A receptor antagonist WAY100135 and its enantiomers on 8-OH-DPAT-induced hyperglycaemia in conscious rats. AB - 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) increases plasma glucose levels in conscious rats probably by stimulation of central 5-HT1A receptors. We have examined the effects of WAY100135 (N-tert-butyl-3-[4-(2 methoxyphenyl)piperazin-1-yl]-2-phenylpropan amide), a selective 5-HT1A receptor antagonist and its enantiomers on plasma glucose levels and on the hyperglycaemia induced by 8-OH-DPAT. (R,S)-WAY100135 (minimum effective dose (MED) 3 mg/kg i.v.) and (S)-WAY100135 (MED 1 mg/kg i.v.) dose-dependently attenuated 8-OH-DPAT induced hyperglycaemia. In contrast, (R)-WAY100135 at doses up to 3 mg/kg i.v. was unable to block hyperglycaemia induced by 8-OH-DPAT. When the antagonists were examined for intrinsic effects on plasma glucose levels only (S)-WAY100135 (3 mg/kg i.v.) caused a significant but transient hyperglycaemia (20% increase). These results are consistent with previous suggestions that (R,S)-WAY100135 and (S)-WAY100135 are selective 5-HT1A receptor antagonists and that 8-OH-DPAT induced hyperglycaemia is mediated by 5-HT1A receptors. The antagonist action of WAY100135 is stereoselective, and more potent activity being observed with the (S) enantiomer. PMID- 8206110 TI - Ryanodine-induced contraction in femoral artery from spontaneously hypertensive rats. AB - The mechanisms of ryanodine-induced contractions were studied in strips of femoral arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Ryanodine (30 nM to 30 microM) alone contracted arterial strips in a dose-dependent manner. The maximum contraction in SHR was about 5 times greater than that in WKY. SHR strips had about a 30 times lower threshold than WKY strips. Pretreatment with ryanodine caused a more potent dose-dependent inhibition of 10 mM caffeine-induced contractions in SHR than in WKY. Ryanodine (10 microM) failed to contract SHR strips in a CaCl2-free solution, whereas caffeine induced a transient contraction in the solution. Under the conditions that the sarcoplasmic reticulum was depleted of Ca2+ by exposure of the strips to the CaCl2-free solution, ryanodine caused a contraction in the presence of extracellular Ca2+. Verapamil (1 nM) to 1 microM) relaxed the strips precontracted with ryanodine in a dose-dependent manner. In WKY strips exposed to a 15 mM K+ solution, ryanodine-induced contractions were potentiated and were not different from those of SHR strips in a normal K+ (5.9 mM) solution. These results suggest that ryanodine contracts rat femoral arteries by promoting Ca2+ influx through voltage-dependent Ca2+ channels, and that the ability of ryanodine to contract the arteries may depend on the state of the Ca2+ channels. PMID- 8206111 TI - Effects of direct and indirect acetylcholine receptor agonists on growth hormone secretion in humans. AB - Cholinergic pathways in the central nervous system positively influence growth hormone (GH) secretion. In fact pyridostigmine, a cholinesterase inhibitor, enhances both basal and GH-releasing hormone (GHRH)-induced GH secretion while, conversely, pirenzepine, an antagonist of muscarinic M1 receptors, inhibits the GH response to GHRH and to other physiological and pharmacological stimuli. The effect of the cholinergic system on GH secretion probably takes place via inhibition of the release of endogenous somatostatin. In this study in 36 normal adults (26 males and 10 females, age 22-35 years) we compared the effects of three cholinesterase inhibitors (pyridostigmine, 120 mg p.o., n = 19; neostigmine, 10 micrograms/kg i.v., n = 6; physostigmine, 12.5 micrograms/kg i.v., n = 6) and bethanechol, a direct muscarinic receptor agonist that is mainly active on muscarinic M3 receptors (25 micrograms/kg i.v., n = 5), on both basal and GHRH (1 microgram/kg i.v.)-stimulated GH secretion. Pyridostigmine, neostigmine and physostigmine induced a significant GH increase (peak vs. basal levels, mean +/- S.E.: 10.4 +/- 1.6 vs. 0.6 +/- 0.2 micrograms/l, P = 0.0001; 13.3 +/- 1.2 vs. 0.5 +/- 1.1 micrograms/l, P = 0.004; and 14.9 +/- 3.1 vs. 2.7 +/ 1.1 micrograms/l, P = 0.025;, respectively). These drugs also induced a similar potentiation of the GH response to GHRH (peak: 48.3 +/- 5.6 vs. 16.2 +/- 2.2 micrograms/l, P = 0.0001; 49.2 +/- 2.2 vs. 19.9 +/- 5.1 micrograms/l, P = 0.006; and 76.9 +/- 12.4 vs. 18.1 +/- 5.3 micrograms/l, P = 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206112 TI - Ethanol affects sympathetic cotransmission and endothelium-dependent relaxation in the rat. AB - The influence of ethanol on sympathetic nerve-mediated contractions of rat tail arteries and on endothelium-dependent relaxation of rat mesenteric arteries by acetylcholine was examined using the method of in vitro pharmacology. Ethanol potentiated sympathetic nerve-mediated contractions. Ethanol had no effect on the neurogenic contractions that remained after alpha-adrenoceptor blockade by prazosin. However, after P2x-purinoceptor desensitisation, the residual nerve mediated contractions were significantly enhanced by ethanol. Contractions to exogenous noradrenaline and alpha,beta-methylene ATP were unaffected by ethanol. It is concluded that ethanol selectively potentiates the noradrenergic component of sympathetic neurotransmission. Ethanol depressed the relaxation by acetylcholine but not that induced by sodium nitroprusside. These results indicate that ethanol can affect both the neural and endothelial control of vascular tone. The potentiated noradrenergic vasoconstrictor response to sympathetic nerve stimulation and the compromised capacity of the endothelium to cause relaxation after ethanol treatment may contribute to the development of vascular diseases associated with alcohol consumption. PMID- 8206113 TI - Influence of aortic baroreceptor denervation on adenosine receptor-mediated relaxation of isolated rat aorta. AB - The effect of aortic baroreceptor denervation on the vasorelaxant activity of the adenosine analogue, 5'-N-ethylcarboxamidoadenosine (NECA) was evaluated in the isolated thoracic aortic rings from rats. The responses were evaluated at 3 h after baroreceptor denervation when the blood pressure was significantly higher than that of control (149 +/- 3 vs. 112 +/- 2 mmHg) and at 48 h after aortic baroreceptor denervation when blood pressure returned to control level. Sham operation had no effect on blood pressure at either time interval. A concentration-dependent relaxation of rat aorta elicited by NECA was observed in all groups. However, the responsiveness to NECA was reduced in aortic baroreceptor-denervated rats. The nitric oxide (NO) synthase inhibitor, L monomethyl-L-arginine (30 microM) shifted the dose-response curve for NECA to the right in all groups suggesting that the vascular response to NECA is partially mediated through the release of NO. Removal of the endothelium abolished the differences in the response to NECA in sham and aortic baroreceptor-denervated rats suggesting that the decrease in the responsiveness of aortic smooth muscle to NECA is dependent on the release of NO. Vasorelaxant responses to acetylcholine were not altered by aortic baroreceptor denervation. The ability of aortic baroreceptor denervation to attenuate vasorelaxant responses to NECA but not to acetylcholine indicated the possibility of functional changes involving adenosine receptor-mediated relaxation in endothelium rather than structural changes due to aortic baroreceptor denervation. These findings suggest that short term elevation of blood pressure following aortic baroreceptor denervation modulates the endothelium-dependent release of NO mediated by adenosine receptor activation. PMID- 8206114 TI - CCK receptor activation may prevent tolerance to morphine in mice. AB - Different groups of mice were treated with morphine (50 mg/kg s.c.) once daily for 1, 2, 3, 4 or 5 days, in order to develop tolerance to the drug. The antinociceptive effect of morphine (9 mg/kg s.c.) was tested 24 h after each dose of the drug administration. Tolerance to morphine reached its peak on the 4th day. Daily pretreatment of animals for a period of 4 days with different doses of cholecystokinin octapeptide (CCK-8; 0.001, 0.01, 0.05 and 0.1 mg/kg s.c.), caerulein (0.0001, 0.001, 0.005 and 0.01 mg/kg s.c.) but not unsulfated cholecystokinin octapeptide (0.001, 0.01 or 0.1 mg/kg s.c.) 30 min before daily administration of morphine (50 mg/kg s.c.) prevented the development of tolerance. A group of animals received a single dose of caerulein (0.005 mg/kg), CCK-8 (0.01 mg/kg) or unsulfated CCK-8 (0.01 mg/kg) 30 min before morphine injection (50 mg/kg s.c.) on the 3rd or 4th day. In these animals, which were tested for antinociception on the 5th day, tolerance to the drug (3, 6 and 9 mg/kg s.c.) was also decreased by caerulein, CCK-8 but not unsulfated CCK-8. In a group of mice in which peptides were administered 30 min prior to the doses of morphine (3, 6 or 9 mg/kg s.c.) on the 5th day, similar results were obtained. The results of the present study indicate that activation of both CCKB and CCKA receptors may prevent the development of tolerance to morphine, and the sulfate group in the CCK-8 molecule may be essential for the tolerance inhibition. PMID- 8206115 TI - BW A4C and other hydroxamic acids are potent inhibitors of linoleic acid 8R dioxygenase of the fungus Gaeumannomyces graminis. AB - Linoleic acid is converted to 8R-hydroperoxylinoleic acid by the soluble 8R dioxygenase of the fungus Gaeumannomyces graminis. Effects of different lipoxygenase inhibitors on the 8R-dioxygenase were evaluated. Three hydroxamic acid derivatives were investigated. BW A4C (N-(3-phenoxycinnamyl)acetohydroxamic acid) was the most potent with an IC50 of 0.2 microM, followed by zileuton (3-10 microM) and linoleate-hydroxamic acid (0.02 mM). Two other lipoxygenase inhibitors, nordihydroguaiaretic acid and eicosatetraynoic acid, were less potent (IC50 0.09 and 0.15 mM, respectively). The 8R-dioxygenase was also strongly inhibited by commonly used buffer additives, dithiothreitol, beta-mercaptoethanol and phenylmethanesulfonyl fluoride. G. graminis also contains a hydroperoxide isomerase, which converts 8R-hydroperoxylinoleic acid to 7S,8S-dihydroxylinoleic acid. Ammonium sulphate precipitation and gel filtration indicated that the dioxygenase and the hydroperoxide isomerase activities could be separated. PMID- 8206116 TI - Role of histamine in allergen-induced asthmatic reactions, bronchial hyperreactivity and inflammation in unrestrained guinea pigs. AB - In a new model using conscious, unrestrained and ovalbumin-sensitized guinea pigs, we investigated the effects of the selective histamine H1 receptor antagonist, mepyramine, on the development of allergen-induced early and late asthmatic reactions, bronchial hyperreactivity and airway inflammation, having each animal as its own control. In guinea pigs responding to a first allergen exposure with an early as well as a late asthmatic reaction (82% of the animals) a second, identical, allergen provocation was performed, in the absence (control) or presence of 1 mg/ml mepyramine aerosol, inhaled for 10 min, 1 h before provocation. The mepyramine treatment significantly reduced both early and late asthmatic reactions and prevented the development of bronchial hyperreactivity to histamine and methacholine after both reactions. Examination of the bronchoalveolar lavage fluid 24 h after the second allergen provocation revealed a general reduction of inflammatory cells after mepyramine treatment. The results indicate that histamine, released during the early asthmatic reaction, contributes to the development of the late asthmatic reaction as well as of early and late bronchial hyperreactivity, possibly via an effect on airway inflammation. PMID- 8206117 TI - Clonidine attenuates conditioned aversion produced by naloxone-precipitated opiate withdrawal. AB - Clonidine, an alpha 2-adrenoreceptor agonist, is used to alleviate withdrawal severity during detoxification from chronic opiate use. The effectiveness of clonidine has been challenged because it attenuates some, but not all, withdrawal signs in humans and animals. Because somatic assessments may not reflect opiate withdrawal aversion, this study used a one-trial place conditioning procedure. Naloxone was paired with the most preferred side and the amount of time spent on this side and on the vehicle-paired side was measured after training. This procedure led to a dose-related decrease in the time spent on the naloxone-paired side in morphine-exposed rats, but not in non-morphine-exposed rats. This conditioned place aversion shown by morphine-exposed rats was significantly attenuated by clonidine. These results suggest that in addition to clonidine's ability to lessen some somatic signs of opiate withdrawal, it also attenuates the aversive aspects of this state. PMID- 8206118 TI - Oedema reduction by levemopamil in focal cerebral ischaemia of spontaneously hypertensive rats studied by magnetic resonance imaging. AB - The effect of treatment with the Ca2+ channel blocker and 5-HT2 receptor antagonist levemopamil (recommended INN for (S)-emopamil) on the extent of ischaemic brain oedema was studied by magnetic resonance imaging in vivo. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent middle cerebral artery occlusion. The treatment consisted of slow intravenous injections of an aqueous solution of levemopamil given immediately after middle cerebral artery occlusion and again 2 h and 4 h later. One group of animals (n = 17) received 3 x 2 mg/kg of levemopamil (total dose: 6 mg/kg) and another group (n = 13) received 3 x 4 mg/kg (total dose: 12 mg/kg). Saline was administered to the controls (n = 16) at corresponding times. High-resolution T2-weighted spin echo images were obtained 24 h after middle cerebral artery occlusion from two transversal brain planes (4.5 mm and 6.5 mm dorsal to the interaural line). Dose dependent reductions of brain oedema were achieved in both brain planes. The lower dose of levemopamil reduced the extent of oedema significantly (P < 0.05) by 20 +/- 3.7% in the upper and by 21 +/- 3.8% in the lower brain plane as compared to the controls (means +/- S.E.M.). The higher dose diminished the extent of oedema in the same planes by 30 +/- 3.5% and 31 +/- 4.0%, respectively. Dose-dependent reductions of infarct size, as determined by vital tissue staining using 2,3,5-triphenyltetrazolium chloride (TTC), were observed in the levemopamil treated groups. Body temperature was not affected by levemopamil, suggesting direct cerebroprotection by this drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206119 TI - Inhibition by topiramate of seizures in spontaneously epileptic rats and DBA/2 mice. AB - The effects of topiramate, a novel antiepileptic drug, on tonic and absence-like seizures in spontaneously epileptic rats (SER; zi/zi, tm/tm) and on sound-induced seizures in DBA/2 mice were investigated. Topiramate (20 and 40 mg/kg i.p.) inhibited both tonic and absence-like seizures in a dose-dependent manner, whereas phenytoin (20 mg/kg i.p.) and zonisamide (40 mg/kg i.p.) inhibited only the tonic seizures. The inhibitory effects of topiramate on absence-like seizures were antagonized by pretreatment with haloperidol (0.5 mg/kg i.p.), but those on the tonic seizures remained unaffected. Topiramate inhibited sound-induced seizures in DBA/2 mice (ED50 = 8.6 mg/kg p.o.). These findings suggest that topiramate may be effective for treatment of both convulsive and absence seizures of human epilepsy. The inhibitory effect of topiramate on absence-like seizures in SER may be mediated through the central dopaminergic system. PMID- 8206120 TI - Modification of effects of chronic electroconvulsive shock by voltage-dependent Ca2+ channel blockade with nifedipine. AB - A single electroconvulsive shock produced analgesia (expressed as prolongation of hot-plate latency) in Wistar rats 45 min after the shock. The analgesic action was prevented by administration of nifedipine, 5 mg/kg i.p., 15 min before the electroconvulsive shock, while nifedipine injection after electroconvulsive shock did not affect the analgesia significantly. At the same time single electroconvulsive shock counteracted the reduction of [3H]nitrendipine binding to cortical and hippocampal membranes from rats pretreated with nifedipine. Chronic administration of electroconvulsive shock (once daily for 8 days) produced hyperalgesia, augmented locomotor responses to low doses of apomorphine and upregulation of cortical (but not hippocampal) voltage-dependent Ca2+ channels (assessed from [3H]nitrendipine binding). In rats receiving electroconvulsive shock chronically, always 15 min after nifedipine injection, neither behavioral hyperresponsiveness nor Ca2+ channel upregulation was observed. The results suggest that the primary event in post-electroconvulsive shock analgesia depends on Ca2+ influx into neurons through voltage-dependent Ca2+ channels, and that given under conditions of Ca2+ channel blockade electroconvulsive shock is unable to trigger changes leading to Ca2+ channel upregulation, and this is possibly the reason for prevention of development of hyperalgesia and increased responsiveness to dopaminergic stimulation. PMID- 8206121 TI - Effects of apomorphine, physostigmine and vasoactive intestinal peptide on penile erection and yawning in diabetic rats. AB - The present report describes for the first time the effects of systemic administration of apomorphine and of physostigmine, as well as the effects of central and systemic administration of vasoactive intestinal peptide (VIP), on penile erection and yawning in rats with streptozotocin-induced diabetes. Systemic administration of apomorphine induced both penile erection and yawning in non-diabetic rats but not in diabetic rats, while that of physostigmine induced only yawning in non-diabetic rats, and neither yawning nor penile erection in diabetic rats. Intracerebroventricular administration of VIP induced both penile erection and yawning in non-diabetic rats, but neither was induced in diabetic rats. Application of VIP as an ointment to the surface of the glans penis induced penile erection but not yawning in both non-diabetic and diabetic rats. Thus, penile erection and yawning are less easily induced in diabetic rats than in non-diabetic rats. Grooming occurred whenever penile erection was induced, but was not associated with yawning. PMID- 8206122 TI - Age-induced alteration of neuromuscular transmission: effect of halothane. AB - Age-induced alteration in neuromuscular transmission and the effect of halothane were examined in 3- and 30-month-old rats with the voltage clamp technique. Significant pre- and post-junctional changes of synaptic transmission occur with advancing age as the frequency of spontaneous release, quantal content and mobilization rate increase and decay time (tau) of miniature end plate current (MEPC) and end-plate current (EPC) is prolonged and altered (bi-exponential). Effects of halothane (0.3-0.88 mM) appeared to be pre-junctional, as the anesthetic decreased the frequency of spontaneous release, end plate current amplitude, quantal content and mobilization rate, had little or no effect on decay time of miniature end plate current and end plate current, and produced no run-down of ionophoretically evoked trains of end plate current. Some of these effects of halothane are more prominent in 30-month-old rats. PMID- 8206123 TI - The kappa-opioid receptor expressed on the mouse lymphoma cell line R1.1 contains a sulfhydryl group at the binding site. AB - Studies were directed at determining whether the kappa-opioid receptor expressed on the mouse R1.1 thymoma cell line contained either a disulfide bond or a sulfhydryl group at the opioid binding site. The binding of the kappa-opioid receptor agonist [3H](-)-bremazocine to R1.1 cell membranes was unchanged following treatment with the disulfide bond-reducing reagent dithiothreitol at concentrations up to 130 mM. However, treatment of membranes with the sulfhydryl alkylating reagent N-ethylmaleimide, followed by extensive washing, reduced [3H]( )-bremazocine binding by as much as 90%. Inhibition of [3H](-)-bremazocine binding by N-ethylmaleimide was concentration- and time-dependent. When R1.1 cell membranes were treated with 1 mM N-ethylmaleimide for 10 min at 24 degrees C, the Bmax value for [3H](-)-bremazocine binding decreased by 50%, with no change in receptor affinity. N-Ethylmaleimide-induced reduction of [3H](-)-bremazocine binding was attenuated by pretreatment of membranes with the kappa-selective opioids U50,488 and U69,593. The results indicate that a sulfhydryl group is present at or near the binding site on the kappa-opioid receptor expressed by the R1.1 thymoma cell line. PMID- 8206124 TI - Modulation of glyceraldehyde-3-phosphate dehydrogenase in Salmonella abortus equi lipopolysaccharide-treated mice. AB - Nitric oxide (NO) is known to inhibit glyceraldehyde-3-phosphate dehydrogenase enzyme activity caused by an NAD(+)-dependent posttranslational protein modification mechanism. In order to study a possible similar protein modification under in vivo conditions, mice were injected with bacterial endotoxin known to endogenously generate NO. In endotoxin-treated mice glyceraldehyde-3-phosphate dehydrogenase enzyme activity was significantly reduced in cytosolic fractions of heart and spleen, compared to 100,000 x g supernatants of untreated control animals. Enzyme activity was unaffected in lung and kidney cytosol of the endotoxin-treated group. Employing the differential NAD(+)-dependent labelling method, glyceraldehyde-3-phosphate dehydrogenase in heart and spleen cytosol of the endotoxin-treated group, versus the control group, had been endogenously modified. These changes were not observed in lung and kidney cytosol of endotoxin challenged animals. Using Western blot analysis no significant changes in the amount of protein (glyceraldehyde-3-phosphate dehydrogenase) in control versus endotoxin-treated animals was detectable. Since an endogenously NAD(+)-modified glyceraldehyde-3-phosphate dehydrogenase occurred in endotoxin-treated mice, at least in some organs, this NO-stimulated posttranslational protein modification mechanism seems to function under in vivo conditions. A covalent protein modification mechanism, rather than differences in the amount of the protein is likely to cause changes in enzyme activity. PMID- 8206125 TI - Differential effects of non-peptidic tachykinin receptor antagonists on Ca2+ channels. AB - The effects of a range of non-peptidic neurokinin receptor antagonists on dihydropyridine binding at voltage-dependent Ca2+ channels from rat skeletal muscle were studied. As previously reported, the binding studies on dihydropyridine binding sites revealed a temperature-dependency effect of the tachykinin NK1 receptor antagonist (+/-)-CP 96345 ((2S,3S)-cis-2-(diphenylmethyl) N-((2-methoxyphenyl) methyl)-1-azabicyclo-[2.2.2.]-octan-3-amine) similar to d cis-diltiazem. Its related homologue CP 99994 ((+)-2S,3S)-3-(2 methoxybenzylamino)-2-phenylpiperid ine) was devoid of such activity. However, RP 67580 (perhydroisoindol-4-one-(3aR,7aR)-7,7-diphenyl- 2[1-imino-2-(2 methoxyphenyl)ethyl]) and SR 48968 ((S)-N-methyl-N-[4-(4-acetylamino-4 phenylpiperidino)-2-(3,4-dichloro phenyl) butyl]benzamide) (tachykinin NK1 and NK2 receptor antagonists) were also potent inhibitors of [3H]PN 200-110 (Isradipine) binding without temperature dependency, indicating that actions on ion channels may contribute to their pharmacological effects. Furthermore, all the compounds had affinity for the D888 ((-)-devapamil) phenylalkylamine site, indicating that many neurokinin antagonists may have affinity for Ca2+ channels. PMID- 8206126 TI - Molecular heterogeneity of the type I GABAA/benzodiazepine receptor complex. AB - We have investigated the presence of alpha 1, gamma 2 and beta 2-3 subunits as part of the type I (high affinity for [3H]zolpidem) GABAA/benzodiazepine receptor from rat cerebral cortex. Three subunit specific antibodies have been used (anti alpha 1, to the C-terminal of rat alpha 1 subunit; anti-gamma 2, to the large intracellular loop of the gamma 2 subunit short form and the monoclonal 62-3G1, specific to beta 2-3 subunits) in immunoprecipitation experiments of the [3H]zolpidem binding activity or the 51,000 Da [3H]Ro 15-4513 photoaffinity labeled peptide (P51). The results indicated that alpha 1 subunit was present in the whole population (90%) of the GABAA/benzodiazepine receptors with high affinity for [3H]zolpidem. We cannot exclude the presence of other alpha subunits co-localized with alpha 1. On the one hand, 70-75% of type I GABAA/benzodiazepine receptor from rat cortex have co-existing alpha 1, beta 2-3 and gamma 2 subunits. We call this type Ia. On the other hand, 20-25% of the type I GABAA/benzodiazepine receptor complex should be constructed by the association of alpha 1 with subunits other than beta 2-3 and gamma 2. We call this type Ib. The identity of these subunits is currently unknown. PMID- 8206127 TI - Discrete activation of transduction pathways associated with acetylcholine m1 receptor by several muscarinic ligands. AB - Activation of transfected muscarinic m1 acetylcholine receptors (m1AChR) has been linked to several signal transduction pathways which include phosphoinositide hydrolysis, arachidonic acid release and cAMP accumulation. In Chinese hamster ovary cells stably transfected with the rat m1AChR gene, carbachol elicited all three responses with EC50 values of 2.6, 3.8 and 76 microM, respectively. However, pilocarpine and the selective muscarinic agonist AF102B activated phosphoinositide hydrolysis (by 94 and 27% vs. carbachol, respectively), while antagonizing carbachol-mediated cAMP accumulation. Carbachol also activated (by 4 fold) adenylyl cyclase in membranes prepared from these cells, indicating independence of this signal from intracellular mediators. Moreover, carbachol and AF102B similarly elevated cytosolic Ca2+ in intact m1AChR-transfected cells. The ligand-selective cAMP accumulation, its independence from Ca2+ and the carbachol activated adenylyl cyclase in membranes suggest that it represents an independent m1AChR-mediated signal, unrelated to phosphoinositide hydrolysis. Selective muscarinic ligands such as AF102B may independently activate distinct signalling pathways, which may be important for designing cholinergic replacement therapy for treating Alzheimer's disease. PMID- 8206128 TI - Activation of human platelet phospholipases C and A2 by various oxygenated triterpenes. AB - Eight structural analogues of oxygenated triterpenes exerted striking differences in activation of human platelets. They are four pairs of stereoisomers and two pairs of positional isomers with varying: 1) acetoxyl/hydroxyl substituents; 2) the position of the substituents at C-3 and C-15; and 3) the stereochemistry of a substituent at C-3. It required a threshold concentration for each agent to cause the concentration-dependent activation. These triterpenes were hydrophobic with < 20% difference in the partition coefficients between 1-octanol and water. They caused differential effects on: inositol triphosphate production; the increase in [Ca2+]i; diacylglycerol formation; phosphatidic acid accumulation, protein phosphorylations and arachidonate release. These agents activated both phospholipases C and A2. The trend of activating phospholipase C was triterpenes with two acetoxyl substituents > one acetoxyl/one hydroxyl substituents > two hydroxyl substituents. In activating phospholipase A2, triterpenes with two acetoxyl substituents were most effective, whereas the paired isomers with a hydroxyl group at C-15 alpha and an acetoxyl substituent at C-3 failed the activation. The results enable one to discuss the possible structure-activity relationship of various oxygenated triterpenes in the activation of both phospholipases C and A2. PMID- 8206129 TI - [3H]A-81988, a potent, selective, competitive antagonist radioligand for angiotensin AT1 receptors. AB - Abbott-81988 (A-81988), 2-(N-n-Propyl-N-[(2'-[1H-tetrazol-5-yl]biphenyl-4- yl)methyl]amino)pyridine-3-carboxylic acid is a potent, competitive, non-peptidic antagonist of angiotensin AT1 receptors. A-81988 was labeled with tritium to high specific activity (16 Ci/mmol) and radioligand binding assays performed in rat liver membranes. [3H]A-81988 bound with high affinity (KD = 0.57 nM) and the KD determined from kinetics assays was similar. Non-specific binding (defined with 10(-6) M angiotensin-II) was very low (< 6% at the KD). The binding of [3H]A 81988 was competitive and exhibited appropriate pharmacological specificity for compounds acting at angiotensin AT1 receptors. These properties demonstrate that [3H]A-81988 will be a useful radioligand for studies of angiotensin AT1 receptors in various tissues. PMID- 8206130 TI - Full and partial agonistic behaviour and thermodynamic binding parameters of adenosine A1 receptor ligands. AB - The inhibitory effect of forskolin-stimulated 3',5'-cyclic monophosphate (c-AMP) synthesis in isolated rat adipocytes has been measured for eight typical adenosine receptor agonists. The percent inhibition was evaluated using concentrations of each compound corresponding to 100 times their Ki, inhibitory binding constants, determined in parallel by [3H]N6-cyclohexyladenosine binding to adenosine A1 receptors on adipocyte rat membranes which guaranteed full receptor occupancy. Some drugs were able to inhibit the forskolin-induced c-AMP accumulation by 100% (full agonists, intrinsic activity = 1) but others only to a lesser extent, ranging from 80% to 50% (partial agonists, intrinsic activities in the 0.8-0.5 interval). These efficacy data were correlated with the thermodynamic binding parameters (free energy, enthalpy and entropy) obtained in rat brain membranes by equilibrium constant measurements and van 't Hoff plots in the 0 degrees-30 degrees C range. The positive correlation between intrinsic activity and entropy changes (r = 0.88, n = 8, P < 0.01) points to the possibility of obtaining information about the full spectrum of activities of adenosine analogues from in vitro binding assays and suggests some considerations on the possible drug-receptor interaction mechanism. PMID- 8206131 TI - Thermodynamic analysis of isoproterenol binding to beta-adrenoceptors in rat lung membranes. AB - The thermodynamic properties of the binding of the beta-adrenoceptor agonist isoproterenol and of the antagonist propranolol to beta-adrenoceptors of rat lung were investigated. We found that in our experimental conditions, the high- and low-affinity binding sites for the agonist displayed different properties: the binding to the high-affinity binding site was entropy-driven with a small increase in enthalpy, while agonist binding to the low-affinity binding site was enthalpy-driven. Binding of isoproterenol in the presence of GTP or its non hydrolyzable analogue GppNHp, and the binding of propranolol were enthalpy-driven with a small increase in entropy. PMID- 8206132 TI - Distribution and developmental change of vasopressin V1A and V2 receptor mRNA in rats. AB - With the reverse transcription-polymerase chain reaction (RT-PCR) method, we examined the tissue distribution of vasopressin V1A and V2 receptor transcripts in newborn and adult rats. In adult rats, vasopressin V1A receptor mRNA was detected in the brain, lung, liver and kidney, whereas vasopressin V2 receptor mRNA was found only in the kidney. In newborn rats, vasopressin V1A receptor mRNA was detected in the brain, liver, heart and kidney, whereas vasopressin V2 receptor mRNA in the kidney and brain. In the newborn rat brain the level of vasopressin V2 receptor mRNA decreased with age, and could not be detected in rats older than 2 weeks. Our results first demonstrated the extrarenal expression of vasopressin V2 receptor in the newborn rat brain. Also, the study showed that expressions of vasopressin V1A and V2 receptor mRNA transcripts are dynamically altered in the process of development. PMID- 8206133 TI - Characteristics of stably expressed human dopamine D1a and D1b receptors: atypical behavior of the dopamine D1b receptor. AB - Human dopamine D1a and D1b receptors were stably expressed in Baby Hamster Kidney (BHK) or Chinese Hamster Ovary (CHO) cells. [3H]SCH23390 saturation experiments indicated the presence of only a single binding site in the D1a expressing cell line with a Kd of 0.5 nM. In D1b expressing cell lines, two binding sites were observed with Kd values of 0.5 and 5 nM in CHO cells and 0.05 and 1.6 nM in BHK cells, respectively. Neither of the receptors affected Ca2+ metabolism whereas they both were coupled in a stimulatory fashion to adenylyl cyclase. The pharmacological profile of both the D1a and D1b receptors as assessed from inhibition of specific [3H]SCH 23390 binding was classical D1-like. Thus, benzazepine derivatives as well as the atypical neuroleptics, clozapine and fluperlapine, exhibited high affinity whereas D2 selective compounds like sulpiride and spiperone had low affinity for these receptors. Besides SCH 23390, only NNC 112, fluphenazine and bulbocapnine were able to discriminate between the two states of the D1b receptor. In case of the D1a receptor, the Ki values obtained in binding experiments were very similar to Ki values obtained from inhibition of dopamine stimulated adenylyl cyclase. In the D1b expressing cell line, the Ki values obtained from inhibition of the dopamine stimulated adenylyl cyclase indicated a significantly better correlation with the state of the D1b receptor showing high affinity for antagonists. In agreement with observations from binding experiments, dopamine was around 20 fold more potent in stimulating adenylyl cyclase via the D1b receptor as compared to the D1a receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206134 TI - Toxoplasma gondii: activity of the polyether ionophorous antibiotic nigericin on tachyzoites in cell culture. AB - Polyether ionophorous antibiotics are widely used prophylactically to prevent coccidiosis in livestock production. The study of the effects of the nigericin on tachyzoites of Toxoplasma gondii clearly demonstrated that very low concentrations of this ionophore (0.05 microgram/ml) were sufficient to inhibit strongly the penetration and totally inhibit the intracellular development of parasites. Both nigericin and epinigericin showed a similar activity against tachyzoite development. However, the activity of abierixicin was 50-fold lower. Such antibiotic concentrations did not seem to affect host cells. Immunofluorescence and electron microscopy showed important changes in the cytology of the antibiotic-treated parasites: they were vacuolated or swollen and were sometimes found burst open, having lost their original shape. The magnitude and the frequency of alterations rose as concentrations in ionophore increased. PMID- 8206135 TI - Experimental induction of bradyzoite-specific antigen expression and cyst formation by the RH strain of Toxoplasma gondii in vitro. AB - The differentiation of Toxoplasma gondii tachyzoites into bradyzoites has been studied experimentally in vitro using the virulent RH strain. The differentiation was monitored by immunofluorescence detection of stage-specific proteins by monoclonal antibodies and by electron microscopy. The expression of bradyzoite specific proteins has been induced by modifying the culture conditions in any of the following three ways: increasing the pH of the culture medium (pH 8), shifting temperature from 37 to 43 degrees C, or performing a sodium arsenite treatment. Interferon-gamma, described as involved in the control of toxoplasmosis in vivo, was inefficient to trigger bradyzoite proteins expression in HFF host cells in vitro. The pH increase and heat treatment, but not the sodium arsenite, induced the formation of cysts whose fine structure was similar to that of cysts found in the brain of mice infected by avirulent strains. Our results therefore show that the tachyzoite-bradyzoite switch is not directly dependent on an immunomodulator, but is likely to arise from an alteration of the environment of the host cell-parasite complex. PMID- 8206137 TI - The effects of experimental fasciolosis on bilirubin metabolism in the rat. AB - The effects of subclinical fasciolosis at various stages of its development on bilirubin metabolism were investigated in rats. Studies were carried out at 3 (initial lesions), 6 (parenchymal degeneration), and 11 weeks (biliary localization of the parasite) after infection with an oral dose of 20 metacercariae of Fasciola hepatica. Both bile flow and bile acid secretion were significantly reduced by Weeks 3 and 6 postinfection, while a significantly increased bile flow was found in the 11-week group. Serum concentration of unconjugated bilirubin was elevated at 3-6 weeks postinfection and that of conjugated bilirubin and the esterified/total bilirubin ratio increased in all infected rats. Biliary excretion of bilirubin mono- and diconjugates was maximally increased by 3-6 weeks, remaining elevated at 11 weeks. No significant change in the biliary diconjugate/monoconjugate ratio was found in any of the groups. UDP-glucuronosyltransferase activity was reduced by Weeks 3 and 6. This was accompanied by a significantly lowered liver cytochrome P450 concentration and an elevation in hepatic heme oxygenase activity. Blood hemoglobin concentration was significantly reduced and reticulocyte count increased by 6 and 11 weeks. Our results indicate that enhanced bilirubin production, cholestasis, and a reduced conjugating activity could be responsible for the changes in plasma and bile pigment composition during the acute stage of fasciolosis. Hemolysis and a high bilirubin excretion are maintained when the parasite migrates into the biliary ducts. PMID- 8206136 TI - Partial characterization of the proteolytic secretions of Acanthamoeba polyphaga. AB - The ocular pathology associated with acanthamoebiasis may result, at least in part, from the excretory and secretory (E&S) products of the active Acanthamoeba trophozoites. To test this hypothesis, the ability of A. polyphaga (ATCC Strain 30461) trophozoite E&S products to digest collagen, the major constituent of the corneal stroma, was evaluated. The secreted proteinases of A. polyphaga were identified using in vitro azocoll degradation, activity-PAGE, radiolabeled extracellular matrix (ECM) degradation, and collagen degradation assays. Inhibitors of serine (phenylmethylsulfonyl fluoride, diisopropyl fluorophosphate), cysteine [benzyloxyphenylalanyl-analyl fluoromethyl ketone, N ethylmaleamide, ethylenediamine tetraacetic acid (EDTA), L-trans-3-carboxyiran-2 carbonyl-L-leucylagmatine], metallo- (1,10-phenanthroline, EDTA, phosphoramidon), and aspartyl (pepstatin A) proteinases were incorporated into the assays. Proteinase activity was detected in trophozoites and the E&S products of trophozoites but not in cysts. The azocoll and activity-PAGE assays indicated the presence of serine and cysteine proteinases, while degradation of the radiolabeled ECM by live trophozoites confirmed not only the presence of serine and cysteine proteinases but also metalloproteinase(s). Most proteinase activity occurred at neutral pH. Incubation of E&S with type I collagen did not yield the typical 3/4:1/4 products characteristic of vertebrate collagenases. These data suggest that E&S products of A. polyphaga contain multiple serine and cysteine proteinases with nonspecific collagenolytic activity and that metallproteinases form an additional minor constituent. PMID- 8206138 TI - Plasmodium ovale: observations on the parasite development in Saimiri monkey hepatocytes in vivo and in vitro in contrast with its inability to induce parasitemia. AB - Exoerythrocytic stage parasites of the human malaria parasite Plasmodium ovale were cultured in vitro by inoculating primary cultures of hepatocytes from Saimiri sciureus boliviensis monkeys with sporozoites. Morphology and size of the liver stages were similar to previous in vivo descriptions in humans and chimpanzees. Saimiri monkeys did not develop parasitemia after repeated inoculations with P. ovale sporozoites. However, liver-stage parasites were observed in liver biopsies performed 7 days after sporozoite inoculation. Together with observations on other parasite development, these results demonstrate that host specificity for many malaria parasites occurs at the blood stage level. Lack of host specificity of primary malaria parasite species for the liver forms the basis for the close relationship existing between human and nonhuman primate malaria species. PMID- 8206139 TI - Echinococcus granulosus: characterization of the electrical potential of the syncytial tegument of protoscoleces incubated in vitro--effect of inhibitors. AB - Upon microelectrode impalements of the tegument of Echinococcus granulosus protoscoleces incubated in Ringer Krebs solution, electrical potential differences of -49 +/- 1 mV, using procedure I, and -53 +/- 1 mV, using procedure II, were recorded. The changes in the electrical potential difference as well as the structural alterations produced by sodium deoxicholate indicate that the observed potentials are established across the apical membrane of the syncytial tegument. The electrical potential difference is primarily dependent on the K+ gradient across the tegumental membrane: a 10-fold increase in the external K+ causes a 30-mV change in the electrical potential. External Na+ concentration changes also affected the electrical potential difference, but altering the external Cl- has no detectable effect. Amiloride, a very well-known blocker of Na+ epithelia channels, produced a reversible hyperpolarization that reached the maximum response at 10(-3) M. Ouabain, 10(-4) M, caused a depolarization in both fresh and Na-rich protoscoleces, although this depolarization was greater and showed a faster onset under the latter condition. It is concluded that the electrical potential difference of E. granulosus protoscolex is generated at the apical tegumental membrane and that it can be experimentally divided into two main components: One of them depends on ionic gradients and membrane permeabilities in accordance with the electrodiffusion predicted by the Goldman, Hodgkin, and Katz equation, while the other depends on the electrogenicity of an active Na+/K+ transport system. PMID- 8206140 TI - Toxoplasma gondii: kinetics of lymphocyte subsets in blood and spleen of perorally infected mice. AB - The blood and spleen lymphocyte subsets and parasite burdens in blood, lungs, and brain were determined serially in C57B1/6 mice infected with an avirulent strain of Toxoplasma gondii. Five mice were sacrificed at various time points after infection; Thy1-2+, Ly5+, CD4+, CD8+, and Ly6c+ lymphocyte subsets and macrophages were determined in blood and spleen by cytofluorometry and parasite burdens were quantified in blood, lungs, and brain by means of a tissue culture method. In infected mice, a large increase in the percentage of CD8+ lymphocytes in blood was observed from Day 14, peaking at Day 21; the percentage of CD4+ lymphocytes was not significantly modified compared with uninfected controls. Analysis of Ly6 antigen expression on T lymphocytes showed that CD8+Ly6c+ cells were largely predominant at the different stages of infection. Similar results were obtained for spleen cells. The marked increase in CD8+Ly6c+ cells in the early phase of infection was associated with the clearance of parasites from the lungs. Furthermore, the proportion of CD8+Ly-6c+ remained high until Day 162, when the infection was at the chronic stage. These results suggest that CD8+Ly6c+ lymphocytes may be involved in the control of toxoplasmosis in the acute phase and in the containment of the infection in the chronic stage. PMID- 8206142 TI - Trypanosoma brucei: mammalian epidermal growth factor promotes the growth of the African trypanosome bloodstream form. PMID- 8206141 TI - Plasmodium falciparum: a region of polymorphism in the 3' end of the gene for the ring-infected erythrocyte surface antigen. AB - A clone expressing the 3' end of the RESA gene of the Palo Alto isolate of Plasmodium falciparum was isolated by screening a lambda expression library of Mung bean nuclease-digested genomic DNA fragments with antibodies from malaria patients. The DNA sequence of the RESA gene of this isolate has seven single-base changes compared to that seen in the Papua New Guinean isolate FC27. Six of the seven mutations cause amino acid substitutions. The same amino acid sequence as the Palo Alto sequence is found in the Ghanaian isolate NF7. To determine whether these are the only changes in this region of the molecule, we performed PCR analyses on 12 blood samples from malaria patients from Indonesia. The Palo Alto form of the RESA gene was detected in 10 of the samples and the FC27 form of the gene was detected in the other 2 samples. No other forms of the RESA gene were found, suggesting that RESA exists in two alleles for the examined region of the gene. These results indicate that there are two major allelic forms of RESA present in this part of Indonesia. PMID- 8206143 TI - On the introduction of genetically modified Leishmania outside the laboratory. PMID- 8206144 TI - Trypanosoma cruzi: murine virus contaminant of the experimental infection. PMID- 8206145 TI - Major surface glycoproteins of procyclic stage African trypanosomes. AB - The procyclic stage in the life cycle of African trypanosomes is adapted for life in the harsh environment of the midgut of the tsetse fly vector. Procyclic forms derived by transformation from antigenically distinct bloodstream variants are antigenically similar and have lost the variant surface glycoprotein coat of the bloodstream forms. In contrast to bloodstream forms, where the variant surface glycoprotein coat is essentially the only molecule exposed, many different proteins can be labeled by surface iodination or biotinylation of procyclic trypanosomes. Despite this multiplicity of procyclic surface proteins, only a few have been characterized in any detail. This minireview focuses on one set of them, the predominant procyclins. PMID- 8206146 TI - Plasmodium: the developmentally regulated ribosome. PMID- 8206147 TI - Intracellular trafficking of glycosphingolipids: role of sphingolipid activator proteins in the topology of endocytosis and lysosomal digestion. AB - Glycosphingolipids (GSL) are components of the outer leaflet of the plasma membrane (PM) of vertebrate tissues. Our current knowledge of GSL metabolism and their intracellular traffic has been derived from metabolic studies but the exact mechanisms by which GSLs are transported from sites of synthesis (endoplasmic reticulum and Golgi) to the sites of residence (PM) and degradation (lysosomes) have not been clearly defined. It is now established that components of the PM reach the lysosomal compartment mainly by endocytic membrane flow. According to a new model, GSLs derived from the PM are thought to end up in intra-endosomal vesicles which could be delivered, by successive processes of membrane fission and fusion, along the endocytic pathway directly into the lumen of the lysosomes. Here the GSLs are degraded in a step-wise manner by exohydrolases. However, the catabolism of membrane-bound GSLs with short hydrophilic head groups needs the assistance of sphingolipid activator proteins (SAPs), which lift the GSLs from the plane of the membrane and present them for degradation to the lysosomal exohydrolases, which are usually water-soluble. The inherited deficiency of one of these enzymes or SAPs causes the lysosomal storage of their respective GSL substrates. In the case of the simultaneous deficiency of all 4 different SAPs the storage of all GSLs with short hydrophilic head groups occurs within multivesicular bodies and/or intra-lysosomal vesicles. PMID- 8206148 TI - Biogenesis of lysosomal membranes. AB - Lysosomal membrane glycoproteins are highly glycosylated proteins decorating the luminal surface of lysosomal membranes. Their biosynthetic route from the rough endoplasmic reticulum to the lysosomal compartment has been elucidated during recent years. Signals for intracellular sorting have been identified and characterized. The function of these proteins remains to be determined. Besides resident proteins the lysosomal membrane harbours at least one transient passenger, lysosomal acid phosphatase, which is sorted as a membrane-bound precursor like resident lysosomal membrane proteins and liberated from the membrane by limited proteolysis upon arrival in dense lysosomes. PMID- 8206149 TI - Water transport across biological membranes. AB - The rate of the lateral diffusion of straight-chain phospholipids predicts the rate of water diffusion through bilayers. A new model of lipid dynamics integrates these processes. Substances such as cholesterol that reduce water diffusion proportionally reduce lateral diffusion. The model yields a number of predictions about the dynamics of the lipids at the Tm and suggests different mechanisms for how water diffuses across bilayers of other-than-straight-chain lipids, and how proteins bind to membranes. A second recent development in water transport across biological membranes is the discovery of a ubiquitous family of water transport proteins that facilitate large-volume water translocation. Like water diffusion through lipid bilayers, water transport by these proteins is directed by osmosis and is therefore under the control of ATP and ion pumps. The presence of water transport proteins in membranes is often regulated by hormones. PMID- 8206150 TI - Biosynthetic lipid-tagging of antibodies. AB - Chemical conjugation of fatty acids to antibodies generates lipid-modified molecules which have found use in the targeting of liposome-mediated drug delivery and in liposome-based immunoassays. Alternatively, bacterial expression of antibodies as single-chain FV fragments fused to lipoprotein signal peptide and N-terminal sequence leads to in vivo enzymatic addition of a single glycerolipid group at the N-terminus of the molecule. This lipid-modification converts the antibody from a soluble protein into a functional membrane-bound molecule. These biosynthetically lipid-tagged antibodies may prove useful for immobilization of antibodies to membranes in various biotechnological applications. PMID- 8206151 TI - Specificity and promiscuity in membrane helix interactions. AB - Transmembrane alpha-helices can associate with one another in lipid bilayers. This association is important in the folding and oligomerization of many integral membrane proteins, and may also play a role in their function. The interactions between helices may be highly specific or relatively non-specific, and their roles may differ accordingly. These two cases are discussed. PMID- 8206152 TI - Prostaglandin H synthase: implications for membrane structure. AB - The crystal structure of the membrane protein prostaglandin H synthase (PGHS) provides strong evidence for the existence of monotopic membrane proteins: PGHS seems to interact with the membrane via a motif of amphipathic helices positioned parallel to the plane of the membrane. The orientation of this unique membrane binding motif is fixed in space by an epidermal growth factor(EGF)-like module on its amino-terminal end and by the catalytic domain at its carboxy-terminal end. The catalytic domain of PGHS has a high structural homology to other mammalian heme peroxidases. PMID- 8206153 TI - Band 3 protein: structure, flexibility and function. AB - The electroneutral exchange of chloride and bicarbonate across the human erythrocyte membrane is facilitated by Band 3, a 911 amino acid glycoprotein. The 43 kDa amino-terminal cytosolic domain binds the cytoskeleton, haemoglobin and glycolytic enzymes. The 52 kDa carboxyl-terminal membrane domain mediates anion transport. The protein is a functional dimer, in which the two subunits probably interact with one another by an allosteric mechanism. It is proposed that the link between the mobile cytoplasmic and the membrane-spanning domains of the protein is flexible, based on recent biochemical, biophysical and structural data. This explains the long-standing puzzle that attachment to the cytoskeletal spectrin and actin does not appear to restrict the rotational movement of the Band 3 protein in the erythrocyte membrane. In the Band 3 isoform from the Southeast Asian Ovalocytes (SAO) this link is altered, resulting a tighter attachment of the cytoskeleton to the plasma membrane and a more rigid red blood cell. PMID- 8206154 TI - The seventh Datta Lecture. Membrane bending energy concept of vesicle- and cell shapes and shape-transitions. AB - The main objective of this lecture is to discuss the role of lipid-bilayer elasticity (1) for the self-organization of lipid/protein-bilayers (2) for the stabilization of domain structures and shapes of cell membranes and (3) for the control of shape transitions (e.g. bud- and pit-formation) and shape instabilities (vesicle fission). It is demonstrated that many complex shape transitions of cell membranes can be mimicked by single lipid bilayer vesicles by simply varying the area-to-volume ratio or by chemically induced bending moments suggesting that these processes are governed by the universal minimum bending energy concept of closed shells composed of stratified membranes. The essential role of the coupling between curvature and phase separation in mixed membranes for the formation and stabilization of local pits and buds or the fission of budded vesicles is demonstrated. Finally, we discuss the consequences of the pronounced thermally excited bending undulations of the hyperelastic membranes for the membrane tension, the material exchange at membrane surfaces and the control of the adhesion of vesicles (or cells) on solid substrates. PMID- 8206155 TI - Structure, transmembrane topology and helix packing of P-type ion pumps. AB - Electron microscopy has recently provided improved structures for P-type ion pumps. In the case of Ca(2+)-ATPase, the use of unstained specimens revealed the structure of the transmembrane domain. The composition of this domain has been controversial due to the variety of methods used to study the number and exact locations of transmembrane crossings within the sequence. After reviewing the results from several members of the family, we found a consensus for 10 transmembrane segments, and also that 10 helices fitted well into the structure of Ca(2+)-ATPase. Thus, we present the most detailed model for transmembrane structure so far, in the hope of stimulating more precise experimental strategies. PMID- 8206156 TI - The role of the stalk in the coupling mechanism of F1F0-ATPases. AB - The extrinsic and intrinsic membrane sectors of F1F0-ATPases are linked by a slender stalk 40-50 A in length. The stalk transmits the energy produced by oxidative or photosynthetic phosphorylation from the intrinsic sector, F0, to the catalytic sites in the extrinsic F1 sector. How this is achieved is unknown, but long-range conformational changes linked to transmembrane proton transport may be involved. In bacterial and chloroplast F1F0-ATPases, the stalk is probably a composite of subunits delta and epsilon, part of the gamma-subunit, and the extrinsic membrane domains of 2 subunits (identical or non-identical according to the species) that are bound to the membrane by their N-terminal regions. The stalk in the bovine mitochondrial enzyme appears to be more complex, and the gamma, delta, epsilon, OSCP, F6, b and d subunits all contribute to it. A bovine stalk complex has been assembled in vitro from bacterially expressed OSCP, F6, b and d, both in the presence and in the absence of F1-ATPase. One molecule of each of these subunits is present in the assembled complex, as there is also in each native F1F0-ATPase assembly. Providing that suitable crystals can be obtained, the stalk complex and the F1.stalk complex may permit the high resolution structure of bovine F1-ATPase to be extended into the stalk domain. PMID- 8206157 TI - Copper pumping ATPases: common concepts in bacteria and man. AB - Recently, four genes encoding putative copper pumping ATPases have been cloned from widely different sources: two genes from Enterococcus hirae that are involved in copper metabolism and two human genes that are defective in the copper-related Wilson and Menkes disease. The predicted gene products are P-type ATPases. They exhibit extensive sequence similarity and appear to be members of a new class of ATP driven copper pumps involved in the regulation of cellular copper. PMID- 8206158 TI - Mitochondrial carrier proteins. AB - Ten mitochondrial carriers have been purified from animal mitochondria. They are small proteins with a molecular mass ranging from 28 to 34 kDa on SDS-PAGE. So far, five of these proteins have been sequenced. Their polypeptide chain consists of three tandemly related sequences of about 100 amino acids. The repeats of the different proteins are related and probably fold into two transmembrane alpha helices linked by an extra-membrane loop. The features of this family are also present in several proteins of unknown function characterized by DNA sequencing. Isoforms of some carriers have been found. All mitochondrial carriers investigated in proteoliposomes function according to a simultaneous (sequential) mechanism of transport. The only exception is the carnitine carrier that proceeds via a ping-pong mechanism. Three mitochondrial carriers have been expressed in yeast and two overexpressed in E. coli and refolded in active form. PMID- 8206159 TI - Maltose transport system of Escherichia coli: an ABC-type transporter. AB - The maltose transport system of E. coli is composed of a periplasmic maltose binding protein (MBP), the presumed transmembrane channel made up of MalF and MalG proteins, and two copies of the ATPase subunit, MalK. The membrane associated transporter complex was purified in a functional form both from the wild-type strain and from mutants that do not require MBP for transport, and was reconstituted into proteoliposomes. A major function of MBP is to send a transmembrane signal, in the presence of ligands, to the ATPase subunits on the inner side of the membrane. In addition, MBP performs a special function in the translocation of the larger ligands, maltodextrins, perhaps by aligning them for entry into the channel. PMID- 8206160 TI - Biochemical characterization of the presecretory protein translocation machinery of Escherichia coli. AB - The protein translocation apparatus in Escherichia coli has been studied both genetically and biochemically. In vitro protein translocation systems involving everted membrane vesicles or reconstituted proteoliposomes have significantly contributed to biochemical clarification of the structure, mechanism and energetics of the apparatus. It is established that SecA, SecY and SecE are essential components, and play fundamental roles in the translocation reaction, and that both ATP and a proton motive force are required for the translocation. A new membrane factor, SecG, was found to participate in the formation of the apparatus, causing significant enhancement of the activity. SecD was found to play a role in the release of translocated proteins from the outer surface of the cytoplasmic membrane. PMID- 8206161 TI - Sec-independent protein insertion into the inner E. coli membrane. A phenomenon in search of an explanation. AB - Translocation of proteins through the inner membrane of E. coli is normally catalyzed by the so-called sec-machinery. Yet, many integral inner membrane proteins appear not to require a fully functional sec-machinery for proper insertion, in spite of the fact that sometimes quite sizable domains have to be translocated to the periplasmic side. This review will focus on recent studies of sec-independent translocation events in an attempt to pin-point the main differences between sec-dependent and sec-independent translocation. PMID- 8206162 TI - Protein translocation: common themes from bacteria to man. AB - Protein transport across the endoplasmic reticulum membrane in eukaryotes and across the cytoplasmic membrane in bacteria have turned out to be highly related. The core component of the translocation apparatus is the Sec61/SecYp complex; at least two of its subunits are conserved in evolution. The Sec61/SecYp complex is involved in both co- and post-translational transport pathways. The two modes require probably distinct additional components. PMID- 8206163 TI - Anionic phospholipids and protein translocation. AB - Anionic phospholipids determine, in diverse ways, the membrane interaction of proteins involved in or undergoing membrane insertion or translocation. How these lipids modulate protein localization, organization, folding and membrane insertion is herein summarized and generalized, leading to a proposal for the function of anionic lipids in cellular transport of newly synthesized proteins. PMID- 8206164 TI - Bifunctional role of the bc1 complex in plants. Mitochondrial bc1 complex catalyses both electron transport and protein processing. AB - Nuclear encoded mitochondrial precursor proteins are cleaved to mature size products by the general mitochondrial processing peptidase (MPP). In contrast to non-plant sources where MPP is a matrix enzyme, the plant mitochondrial MPP is localised in the inner membrane and constitutes an integral part of the bc1 complex of the respiratory chain. Core proteins of the complex are immunologically related and show high sequence similarity to the MPP subunits from non-plant sources. The bc1 complex in plants is thus bifunctional, being involved both in respiration and in protein processing. PMID- 8206166 TI - Bacterial protein toxins penetrate cells via a four-step mechanism. AB - Bacteria produce several protein toxins that act inside cells. These toxins bind with high affinity to glycolipid or glycoprotein receptors present on the cell surface. Binding is followed by endocytosis and intracellular trafficking inside vesicles. Different toxins enter different intracellular routes, but have the common remarkable property of being able to translocate their catalytic subunit across a membrane into the cytosol. Here, a toxin modifies a specific target with ensuing cell alterations, necessary for the survival and diffusion strategies of the toxin producing bacterium. PMID- 8206165 TI - VIP21-Caveolin, a protein of the trans-Golgi network and caveolae. AB - VIP21-Caveolin is a component of the filamentous coat surrounding the invaginations of the plasma membrane called caveolae. Unlike the vesicular coat proteins identified so far, VIP21-Caveolin can be classified as an integral membrane protein. Furthermore, it is found in high molecular mass oligomers. Based on its localisation in specialised membrane subdomains, a role for VIP21 Caveolin in membrane protein sorting has been proposed. PMID- 8206167 TI - Endocytosis and intracellular sorting of ricin and Shiga toxin. AB - Ricin and Shiga toxin belong to a group of protein toxins with targets in the cytosol. These toxins consist of one moiety that binds the toxin molecule to cell surface receptors, and another enzymatically active moiety that enters the cytosol after endocytic uptake of the toxin. The toxins are of current interest in relation to disease and the construction of immunotoxins. Moreover, they have proven useful to investigate mechanisms of endocytosis and to follow intracellular pathways of transport. Some of the recent results obtained with ricin and Shiga toxin are discussed. PMID- 8206168 TI - The major histocompatibility complex in man. AB - The HLA system is a complex of polymorphic genes divided into a class I group and a class II group. The disclosed tertiary structure of HLA antigens indicates that they are principally involved in binding a variety of self and foreign immunogenic peptides and in their presentation to T cells. Class III HLA region is located between class I and class II regions. It comprises many genes, some of them participate in events of the immune response, too. PMID- 8206170 TI - Microwave-induced lipid peroxidation in liposomes. AB - Measuring absorption spectra of conjugated dienes it has been shown that microwave radiation with a frequency of 2.54 GHz induces lipid peroxidation of phosphatidylcholine liposomes. The relationship with the previously observed microwave-enhanced liposome permeability is discussed. PMID- 8206169 TI - Induction of inflammatory cytokines by Nocardia fractions. AB - NDCM and NLD fractions of Nocardia opaca cell walls were used for in vitro stimulation of human and porcine peripheral blood mononuclear cells. Inflammatory cytokines IL-1, IL-6, tumour necrosis factor (TNF) alpha and interferon (IFN) gamma were detected at the single-cell level using paraformaldehyde-fixed and saponin-permeabilized mononuclears stained with cytokine-specific antibodies and indirect immunofluorescence method. IL-1, IL-6 and TNF were produced by human monocytes stimulated for 2 h, IFN gamma-positive lymphocytes were detected later. IFN gamma was produced also by activated porcine lymphocytes. Cells expressing apoptotic features were found among blood mononuclears treated with Nocardia fractions. PMID- 8206171 TI - The role of HLA-DQ antigens in the induction of cytotoxic T lymphocytes. AB - Investigating three pairs of HLA-DR (DRB1) identical unrelated persons on the induction of cytotoxic T lymphocytes (CTL) it was found that HLA-DQ antigens provided slight proliferative stimulus which was, however, sufficient for the generation of CTL. The results indicate that the HLA-DQ antigens do play a similar role in clinical bone marrow transplantation as the HLA-DR specificities. PMID- 8206172 TI - Inhibition of hepatitis B virus surface gene expression by antisense oligodeoxynucleotides in a human hepatoma cell line. AB - We have studied the inhibitory effect of antisense oligodeoxynucleotides on the expression of hepatitis B virus surface antigens. Human hepatoma cell line PLC/PRF/5 harbors several integrated copies of the HBV genome and produces and secretes hepatitis B virus surface antigen (HBsAg) to the medium. Synthetic antisense oligodeoxynucleotides complementary to various regions of the surface antigen gene were synthesized and their ability to block its expression was tested. Oligodeoxynucleotides (17- and 21-mers) complementary to regions covering ATG codons of both preS2 and S genes significantly inhibited preS2 and S protein production. Less efficient inhibition was achieved when the oligonucleotide complementary to the inside S gene region was assayed. PMID- 8206173 TI - Comparison of methods used for detection of mycoplasma contamination in cell cultures, sera, and live-virus vaccines. AB - Two methods for detection of mycoplasma contamination in cell cultures, sera, and live-virus vaccines were compared: the direct culture test and the DNA staining method employing bisBenzimide (Hoechst No. 33258). Contamination by different species of mycoplasma was found in 39% samples tested. It is recommended to use both techniques for a reliable detection of mycoplasma contamination. PMID- 8206174 TI - Minor preprosthetic surgical procedures. AB - Minor preprosthetic surgical procedures used in correcting an existing problem or in preparing the mouth for prostheses must be based on an exact diagnosis and carefully planned and executed to satisfy clearly definable goals. This article emphasizes that philosophy and includes surgical techniques for managing commonly encountered problems as well as those problems associated with placement of immediate dentures. Predictable results with minimal complications can be expected when one adheres to these guidelines. PMID- 8206175 TI - Surgical extractions. AB - The principles of exodontia as they pertain to surgical extractions are presented in this article. A system of presurgical analysis that will alert the dentist to potential problems is outlined. Also, classic techniques of surgical extractions and root retrieval are presented. PMID- 8206176 TI - Pharmacologic considerations in the management of oral surgery patients in general dental practice. AB - Minor oral surgery is an integral part of dentistry, whether performed by the generalist or the specialist. Procedures include those within the broad discipline of general oral surgery (such as routine and surgical extractions, impactions, preprosthetics, biopsy, and implants), periodontics (such as periodontal surgery, mucogingival plastic surgery, and implants), and endodontics (periapical surgery). There is considerable overlap among generalists and surgical specialists in terms of the treatment provider. Perhaps the most important consideration with regard to appropriateness and quality of care is not who does the surgery but how it is done. The ability to perform surgery according to sound surgical principles and to properly prescribe medications in association with that surgery is a necessary requisite for quality treatment. This article reviewed how various pharmacologic agents can be administered and how they influence surgical procedures. Whether or not they are used and the manner in which they are used are predicated on the discretion and clinical judgment of the clinician on a case-by-case basis. If used appropriately, these medications can be instrumental in mitigating morbidity and increasing tolerance and overall patient satisfaction with the surgical experience. PMID- 8206177 TI - The removal of impacted third molars. Principles and procedures. AB - This article reviews factors relating to the removal of impacted third molars. It covers indications for surgery and how indications and surgical difficulty correspond with the age of the patient. The difficulty of the procedure depends not only on age, but on how the tooth is categorized radiographically (classification, position, angulation) and on the patient's facial characteristics (tapering versus compact facial form). The operator's familiarity with the anatomy of the surgical site is indispensable for uneventful third molar surgery. A signed consent form is necessary to meet medico-legal standards. With a diagnosis, treatment plan, and consent to proceed, these teeth are extricated from their sockets with a modicum of instruments, each one fulfilling a specific purpose. The surgical procedure, whether maxillary or mandibular, can be broken into separate segments for technique elaboration and refinement. These segments are flap development, bone removal, luxation, sectioning, tooth removal, and closure. Specific methods may vary among dental surgeons based on training and experience, but they all should correspond to basic and established principles of surgical technique. Some of these principles and techniques have been outlined in describing the removal of typical mandibular and maxillary third molar impactions. PMID- 8206178 TI - Oral mucosal biopsy procedures. Excisional and incisional. AB - Incisional and excisional biopsies of oral mucosal lesions are procedures the dental practitioner should employ for total patient care. Indications and contraindications for obtaining biopsy specimens are outlined in this article. Also, basic and adjunctive surgical techniques are described with an emphasis on a continuum of care until resolution. PMID- 8206179 TI - Apicoectomy and retroseal procedures for anterior teeth. AB - Thirty-five years ago, the terms apicoectomy, semilunar flap, and failure characterized the scope of endodontic surgery. During the intervening years, basic research and clinical experience have catapaulted this area of dentistry to a level of refinement at which consistent long-term success is virtually assured. In summary, it is important to recall the principles of endodontic surgery that dictate treatment. The most important include the following: (1) The semilunar flap must be disregarded; (2) an "apicoectomy" is virtually never definitive treatment and referring to endodontic surgery as an "apicoectomy" should be discouraged; (3) careful considerations must be paid to all factors governing flap design. Finally, it must be realized that although periapical surgery has become a far more predictable treatment, it still is not a substitute for conventional endodontics, except in very rare situations. PMID- 8206180 TI - Intentional replantation. A viable alternative for selected cases. AB - When conventional endodontic treatment or retreatment is not possible, the operator may choose to intentionally extract and replant the involved tooth. Intentional replantation consists of extracting the tooth, finding and correcting the defect, and replanting the tooth in its socket. This article discusses the indications, contraindications, and recommended techniques for intentional replantation. Several successful case reports are described in which intentional replantation was used as a last resort. PMID- 8206181 TI - [Economic analysis and public health. Why does one need economic evaluation applied to diabetes? What methods does one choose: cost effectiveness, cost utility, cost benefit? Are such studies useful in terms of public health?]. AB - The application of economic methods to public health is relatively recent and linked to the context of economic crisis: cooperation between medical doctors is to day in process. The main objective of health economics is the optimization of health care by improving resources allocation to take care of the patients. So, in France, the health system budget, 573 billions, represents 8.3% of the GNP; this percentage is one of the highest of Europe. Can such a growing rate decrease or are we going towards rationing of health system resources? In this context, economic analysis applied to diabetes uses mainly evaluation methods: cost effectiveness, cost-utility, cost-benefit. Evaluation always supposes a comparison between medical alternative actions in terms of costs and results. Economic crisis made easier the acceptance of evaluation studies but their development supposes great scientific caution. PMID- 8206182 TI - [Interest in amd methodology of medical-economic studies in perspective]. AB - Clinicians and economists must collaborate for conception and achievement of clinical-economic studies. If economists are more involved in some decisions such as costs or perspectives selection, other aspects such as general design, data collection methods, endpoints, comparator or procedures must be chosen both by clinicians, epidemiologists and economists. This is the condition for a good data validity, a wide diffusion and exploitation of clinical-economic studies in the future. The introduction of this type of studies should bring interesting data on the care of diabetic patients. PMID- 8206183 TI - [The French diabetic population. Results of a study using a representative sample]. AB - The aim of this study was to assess the prevalence of diabetes mellitus in France, the existing treatment used and the effect of this chronic disease on everyday life patterns of the diabetic population. A survey was undertaken by Lilly laboratories and SOFRES medical institute from November to December 1992, which involved randomly screening 20,000 french families. After the screening questionnaire was sent at to the 20,000 families, the following feedback was obtained: 996 patients have been identified. More than 80% of the patients (that is, 122 were insulin treated and a further 674 were identified as NIDDM) replied to the second self assessment questionnaire. It was possible to make an estimation of the prevalence of diabetes mellitus in France that is to say: 1.9% of the general population. The general practitioner makes the primary diagnosis in more than 80% of the cases, and treats 97% of the NIDDM patients and 74% of the insulin treated diabetic patients. The diabetic patients have an average of 8 consultations per year with their general practitioners and 3-4 consultations per year with the endocrinologist. Therapeutic management of the NIDDM patients is based mainly on diet (82%) alone or in association with drugs. 32% of patients primary treated by drugs and secondary by insulin are not satisfied with their glycemic control (vs 22% of IDDM patients and 15% of NIDDM patients). Less than 35% of diabetic women are current users of contraception. More than one third of children who were born from a diabetic mother had a birth weight above 4 kgs. PMID- 8206184 TI - [Cost of training a diabetes mellitus patient. Effects on the prevention of amputation]. AB - Cost of disease is a complex notion: financial cost, psychological cost for those who have cope with a chronic disease. But there is also another cost which has not yet sufficiently been taken into account: the cost of resistance to change. It has largely been shown that patient education could result in major cost saving as well as improvement of quality of life. Why is there such a resistance from health care providers, health policy planners for implementation of patients education programs? These resistances may well be part of the real cost of efficient control of a disease and like in the case of diabetes, prevention of acute and chronic complications. Education and training of patients has enabled us to decrease markedly lower extremities amputations: 12 times less above knee amputations, reduction by half of below knee amputations and a four fold decrease of toe amputations at the University Hospital of Geneva, Switzerland. PMID- 8206185 TI - [Investment of the associations: Aide aux Jeunes Diabetiques as a model]. AB - This paper describes the action of an association known as l'Aide aux Jeunes Diabetiques, in terms of education, by the organization of summer camps and of regional and national meetings, of information, through these meetings and the diffusion of a quarterly journal, and or research. PMID- 8206186 TI - [Public financial support of research on diabetes in France]. AB - The financial support of any kind of research reveals the interest of a country in a disease. Does the diabetes represent a priority in France? The answer is difficult because the lack of analytical approach of the resources devoted to medical research. For example, many basic works (physiology of metabolism, lipids, different hormones etc.) are not officially referred to diabetes. Moreover when diabetes is a key word of an unit it general only a part of this unit is concerned. The results were provided mainly by CNRS and INSERM and they must be compared to the financial weight of this disease for the collectivity. This evaluation remains imprecise. PMID- 8206187 TI - [Cost of treatment using portable infusion pumps for subcutaneous insulin. State of the experiment in Lyon]. AB - Since the treatment of insulin-dependent diabetics by subcutaneous insulin infusion device is not chargeable to French Health Insurance, charitable associations have been created whose activities are now controlled by the hospitals. A study of the capital and revenue budget of one such association, ADENOTECH, in Lyon, shows that the direct cost of outpatient treatment by portable devices has gone down from 40 F to 22 F per day, of which half represents the capital cost and half running costs. This cost is 15 F more per day than an intensive course by three daily insulin injections. PMID- 8206188 TI - [Cost benefits of intensive insulin therapy using injections, external pumps and implantable pumps]. AB - Since feasibility is now proven, cost-efficacy of external sub-cutaneous (EXT) and implantable programmable (IMP) insulin pumps needs to be compared to those of intensified conventional insulin therapy (CONV). Only metabolic efficacy and short-term direct costs are easily evaluable. We (WHO-CSII Study) and others have shown that glycemic control and severe hypoglycemia risk are slightly improved, while ketoacidosis risk and costs are aggravated with EXT vs CONV. We (CEDIT Study) and others have shown that glycemic control, mild and severe hypoglycemic risks are improved, with no increase in ketoacidosis rates although a doubling in costs with IMP vs CONV. Rigid interpretation of the above data would limit indications of insulin pumps to patients experiencing frequent hypoglycemias while on intensified conventional insulin therapy. PMID- 8206189 TI - [Cost-benefit analysis of education programs and of treatment in type 2 diabetes]. AB - Structured teaching and treatment programmes for Type-II non insulin dependent diabetic patients have been proved in several studies to be cost effective. K. Davidson in Atlanta described the considerable decrease of health care costs after the introduction of his programme. Recently a similar programme was introduced into the German health care system and physicians in private practice are remunerated for providing the programme. Until now more than 10,000 physicians have participated in postgraduate courses, which are the prerequisite to be remunerated. The evaluation of the programme including a cost benefit analysis demonstrated the financial benefits of the programme even in a short time. The methods of nation-wide multiplication of the programme and its contents are summarised in this article. The principles of the treatment strategy follows the objectives which have been published already in 1875 by A. Bouchardat: Urine testing, hypocaloric diet and exercise. PMID- 8206190 TI - [Standardized ambulatory insulin therapy of initial moderate ketoacidosis in type 1 diabetes. A pilot project]. AB - Most textbooks advise that newly diagnosed insulin dependent mellitus be admitted to the hospital for starting carefully insulin treatment. We report a pilot study for starting an outpatient insulin using continuous subcutaneous insulin infusion. In 40 newly IDDM (glycaemia over 16.5 mM/l, CO2 over 15 mM/l), intensive therapy was done by CSII = basal rate 1 unit/hour, bolus 5 units per meal. After a long explanatory talk (4 hours) with the physician and the nurse on hypo, hyperglycaemia, on blood glucose sensor and pump, 21 patients agreed to start insulin at home and 19 remained in hospital for 2 or 7 days. At days 3, 30 and 365, clinical and biological evaluation was done and at D30 patient education program for 5 days was undergone. Never emergency even was reported in any patient, and no difference appeared between the in and out patient in D1, D3 and D365 normalisation of blood glucose (3 days) or level cetone body (2 days) and total insulin dose. Our results suggest that outpatient is a safe and cost effective IDDM onset therapy. PMID- 8206191 TI - [Cost of the diabetic foot]. AB - Among the long term complications of diabetes, leg and foot problems frequently associated with chronic nonhealing wounds constitute a heavy economic cost previously evaluated in some countries. This specific cost has not yet been calculated in France. This study represents the first "estimation" of the frequency and cost of these complications in our country. Methodological obstacles must be considered related to a large variety of clinical situations all covered by the word "diabetic foot", neurotrophic or ischemic origin, and the heterogeneity of the therapeutical approach more or less expensive. We have estimated the incidence of leg and foot problems about 50,000 to 60,000 per years, 20,000 to 25,000 requiring an inpatient treatment for a neurotrophic complication and 10,000 to 15,000 for an ischemic problem (frequently followed by a limited or a large amputation). The annual total cost, direct plus indirect, calculated on this basis should be: 3,750 millions of francs/year (about 700 millions of US $). This value must be compared to the total cost of diabetes in France 12,000 to 18,000 millions of francs/year when considering 1 to 1.5 million diabetic patients. Thus leg and foot problems appear to constitute a prominent part of the economical cost of diabetes in our country as in others developed countries. Multidisciplinary and specialized structures for the care and prevention of such complications of diabetes must be developed as new therapeutical approaches to reduce this incidence, the duration of healing and the risk of relapse. PMID- 8206192 TI - [Cost of the treatments of arterial hypertension associated with diabetes]. AB - In insulin-dependent and non insulin-dependent diabetic patients, the treatment of a modest increase in blood pressure values has been proved effective in reducing the incidence and in improving the evolution of various locations of diabetic angiopathy. This beneficial effect is associated with a cost which can be evaluated by the analysis of IMS and DOREMA data. In France, the evolution of the sales of antihypertensive agents in diabetic patients increased from 117 MF in 1980 to 784 MF in 1991. This dramatic increase is mainly related to the prescription of new antihypertensive agents: calcium antagonists and ACE inhibitors. From 1980 to 1991, the evolution of antihypertensive agent's sales was more important in diabetic patients than in the general population. In 1991, the total cost of antidiabetic treatment: insulin, antidiabetic oral agents and strips for capillary blood glucose monitoring was about 1,100 MF, quite similar to the cost of antihypertensive and hypolipidemic agents used in the same patients. PMID- 8206193 TI - [Balance sheet of CETRADIM after 10 years of functioning as an alternative to hospitalization]. AB - CETRADIM (Educational Centre for the Treatment of Diabetes and Nutritional Diseases) is a hospital department of the Roubaix (France) general hospital functioning uniquely as an alternative to conventional hospital care (outpatient clinics, day hospital, weekday hospital). Its catchment area is essentially local, covering a population of about 200,000. Its vocation is triple: care (including education), training and the supply of information to the treating team and general public. The aim of this study was to evaluate the effect of the existence of a unit of this kind on the frequency of admission of patients for conventional hospital care to the various medical departments of the Roubaix hospital. The indicator used was the percentage of conventional hospitalisation (PCH) in the Endocrinology/Diabetology/Nutrition department, calculated by dividing the number of conventional hospital stay in this specialty by the total number of hospital stay days. Data were obtained for the Roubaix hospital and for 3 hospitals in the Northern region serving comparable types of population but lacking any institution functioning totally as an alternative to hospital care. The PCH was 4.3% for the Roubaix Hospital Centre and 8.2, 8.46 and 10.6% respectively for the other three hospitals. These findings suggest that the existence of an institution such as CETRADIM reduces the number of conventional hospital stay days of patients with Endocrine/Diabetes/Nutrition diseases. Its effects on the constitution of new local care units is discussed, and arguments in favour of its role in the improvement of health care and education costs developed. PMID- 8206194 TI - [DiabCare tools for the control of permanent improvement of the quality of care in diabetes]. AB - The St-Vincent declaration supported by WHO/IDF Europe is a vast european program for the improvement of health care and a new strategic approach to the treatment of diabetes. The DiabCare project is to serve as a tool for verification and assessment. Continuous improvement in diabetic patient care could be facilitated by: making comparison between centres, like "looking into a mirror where one can see oneself and the others at the same time"; setting up health care networks (local, regional and national) for all the professionals involved in treating diabetes; promoting and using advanced computer techniques ("smart" health care card). DiabCare-France, created by the "Conseil Superieur du Diabete", has completed its first task, an "inventory questionnaire", sent to 150 diabetes centres located throughout France. PMID- 8206195 TI - [Cost benefit of screening for type 1 diabetes. A futuristic scenario]. AB - The current knowledge on prediction of Type 1 diabetes derives from family studies, as for example the BOX Study in England. Data indicate that first degree relatives with islet cells antibodies > or = 20 JDFu have a 35% risk to develop the disease within 5 years. But sensitivity and specificity of this risk marker are not high enough to allow for population screening. The tools for Type 1 diabetes screening in the background population are not known yet. Cohort studies have been initiated in different countries but the conclusions on the predictive value of risk markers are not ready. It is already established that both genetic and immunological markers will be necessary to identify individuals with an increased risk in the general population. Evaluation of cost/benefit ratio varies with the strategy for Type 1 diabetes screening. The ENDIT project can be taken as an example. It is an international trial using Nicotinamide for the prevention of the overt phase of Type 1 diabetes in high immunological risk individuals. To implement this model in first degree relatives is feasible and realistic and does not generate additional costs. Conversely the extension of this model to the background population raises many questions such as health structures, additional costs, budget and feasibility... This approach emphasizes the value and the need for epidemiological projects on risk factors of Type 1 diabetes, mainly in the background population, so that new strategies can be rapidly developed when the right preventive treatment is available. PMID- 8206196 TI - Regulation of pancreatic B-cell glucokinase and GLUT2 glucose transporter gene expression. PMID- 8206197 TI - Investigating lipopolysaccharide-binding proteins in serum using biotin-labelled lipopolysaccharide. PMID- 8206199 TI - Surfactant proteins A and D. PMID- 8206198 TI - Inhibition of two gluconeogenic enzymes by glycosylphosphatidylinositol: a model for insulin action. PMID- 8206200 TI - Interactions of carbohydrates and lectins with complement. PMID- 8206201 TI - Mannosamine is an unspecific inhibitor of glycosyl-phosphatidylinositol biosynthesis in T-lymphocytes. PMID- 8206203 TI - Ca2+ and pancreatic B-cell function. PMID- 8206202 TI - The study of neurohypophyseal hormone receptors by ligand binding. PMID- 8206204 TI - Evaluation of creatine kinase isoenzyme isoforms in acute myocardial infarction patients. PMID- 8206205 TI - Neuropeptidases: candidate enzymes and techniques for study. PMID- 8206206 TI - Capillary electrophoresis for peptides, including neuropeptides. PMID- 8206207 TI - Pentosidine content in skin collagen from type II diabetic patients. PMID- 8206208 TI - Some neurochemical applications of electrospray ionization-mass spectrometry. PMID- 8206209 TI - Strategies in studies on neuropeptide processing using mass spectrometry. PMID- 8206210 TI - An investigation into the proteolytic cleavage of Alzheimer amyloid precursor protein in PC-12 cells. PMID- 8206211 TI - Nuclear magnetic resonance studies of peptides and their interactions with receptors. PMID- 8206212 TI - High-affinity analogues of neuropeptide Y containing conformationally restricted non-proteinogenic amino acids. PMID- 8206213 TI - Is there a common intracellular bioreactor in which amyloid formation is initiated in neurodegenerative diseases? PMID- 8206214 TI - Multiple dopamine receptors: relevance for neurodegenerative disorders. PMID- 8206215 TI - Aggregation of Alzheimer's peptides. PMID- 8206216 TI - G-protein coupled signal transduction systems in the Alzheimer's disease brain. PMID- 8206217 TI - Systemic ascorbate protects against kainate neurotoxicity. PMID- 8206218 TI - Amyloidosis in Alzheimer's disease. PMID- 8206219 TI - Amyloid precursor protein gene mutation at codon 670/671 in familial Alzheimer's disease in Sweden. PMID- 8206220 TI - Mechanisms of pancreatic B-cell dysfunction and glucose toxicity in non-insulin dependent diabetes. PMID- 8206221 TI - Similarities between mitochondrial and bacterial electron transport with particular reference to the action of inhibitors. PMID- 8206222 TI - The glycine decarboxylase system in higher plant mitochondria: structure, function and biogenesis. PMID- 8206223 TI - Protease maturation of the Rieske iron-sulphur protein after its insertion into the mitochondrial cytochrome bc1 complex of Saccharomyces cerevisiae. PMID- 8206224 TI - A novel trypsin-like enzyme in breast cancer. PMID- 8206225 TI - Topographical distribution of redox centres and the Qo site in ubiquinol cytochrome-c oxidoreductase (complex III) and ligand structure of the Rieske iron sulphur cluster. PMID- 8206226 TI - Modelling the three-dimensional structure of cytochrome b. PMID- 8206227 TI - Binding sites involved in the formation of the C3 (H2O)-factor B complex of the alternative pathway of complement. PMID- 8206228 TI - The detection of serine elastase in human breast cancer. PMID- 8206229 TI - Inhibitor binding to the Qp-site of bc1 complex: comparative studies of yeast mutants and natural inhibitor resistant fungi. PMID- 8206230 TI - Natural variation in the potency and binding sites of mitochondrial quinone-like inhibitors. PMID- 8206231 TI - B-loop analogues of human epidermal growth factor; design, expression and properties. PMID- 8206232 TI - Acridones and quinolones as inhibitors of ubiquinone functions in the mitochondrial respiratory chain. PMID- 8206233 TI - Effects of analogues of MOA-stilbene on the chloroplast cytochrome bf complex. PMID- 8206234 TI - Effect of different carbon sources on heterologous expression levels in the yeast S. cerevisiae BJ2168. PMID- 8206235 TI - We have the key, can we build a lock? A strategy for the elucidation and molecular modelling of the methoxyacrylate (Qo) binding site of cytochrome b. PMID- 8206236 TI - Two binding sites for naturally occurring inhibitors in mitochondrial and bacterial NADH:ubiquinone oxidoreductase (complex I). PMID- 8206237 TI - Are bioavailable glutamine and sensitivity to hydrochloric acid DNA denaturation important colorectal tumour characteristics? PMID- 8206238 TI - New inhibitors of complex I of the mitochondrial electron transport chain with activity as pesticides. PMID- 8206239 TI - A mutant form of the succinate dehydrogenase iron-sulphur protein subunit confers resistance to carboxin in the maize smut pathogen Ustilago maydis. PMID- 8206240 TI - Synthetic studies on electron transport inhibitors related to natural products. PMID- 8206241 TI - Measuring Kupffer cell clearance capacity (KCCC) using an isolated hepatic perfusion technique. PMID- 8206242 TI - The thiourea insecticide diafenthiuron inhibits mitochondrial ATPase in vitro and in vivo by its carbodiimide product. PMID- 8206243 TI - Uncoupling activity and pesticidal properties of pyrroles. PMID- 8206244 TI - Insecticides and acaricides which act at the rotenone-binding site of mitochondrial NADH:ubiquinone oxidoreductase; competitive displacement studies using a 3H-labelled rotenone analogue. PMID- 8206245 TI - The role of IL-6 in the pathophysiology of jaundice. PMID- 8206246 TI - Role of cytokines in regulation of pancreatic B-cell function. PMID- 8206247 TI - Identification of human plasma proteins using the Laemmli method of gel electrophoresis. PMID- 8206248 TI - Effect of urea cycle intermediates on urea formation from ammonium chloride in rats fed protein-free diet. PMID- 8206249 TI - Biochemical parameters in endurance training. PMID- 8206250 TI - Comparison of two fluorescent probes for the study of erythrocyte membrane fluidity. PMID- 8206251 TI - Binding of C-reactive protein to Leishmania. PMID- 8206252 TI - The use of 13C n.m.r. and saturation transfer to detect tetrahedral intermediates in reactions catalysed by chymotrypsin and also in an amide inhibitor complex. PMID- 8206253 TI - A 13C-n.m.r. study of cyanylated beta-lactoglobulins. PMID- 8206254 TI - D-cycloserine as an affinity ligand for L-alanine aminotransferase in aqueous two phase systems. PMID- 8206256 TI - Lipid peroxidation, LDL glycosylation and dietary fish oil supplementation in type II diabetes mellitus. PMID- 8206255 TI - The effects of continuous ambulatory peritoneal dialysis and haemodialysis on erythrocyte membrane fluidity. PMID- 8206257 TI - Measurement of changes in human apolipoprotein B levels in triglyceride-rich lipoproteins following a fatty meal. PMID- 8206258 TI - Effects of low density lipoprotein of varying composition on cholesterol levels in human monocyte-derived macrophages. PMID- 8206259 TI - Islet cell defence and repair mechanisms in insulin-dependent diabetes: a role for the pancreatic regenerating (Reg) gene? PMID- 8206260 TI - Gastric inhibitory polypeptide--its metabolic effects in sheep. PMID- 8206261 TI - Identification of a novel cell wall-associated endopeptidase in Lactococcus lactis subspecies cremoris SK11. PMID- 8206262 TI - Glucose-6-phosphatase from liver nuclear envelopes. PMID- 8206263 TI - N-(4-azido benzoyl)FnLRFamide, a putative photoaffinity label for the FMRFamide receptor. PMID- 8206264 TI - Nuclear envelope glucose-6-phosphatase from control and thioacetamide treated liver. PMID- 8206265 TI - Pseudomonas citrate synthase: purification and characterisation. PMID- 8206266 TI - Analysis of microgram quantities of glycosaminoglycan in milligram samples of microdissected synovial intima. PMID- 8206268 TI - A study of the tryptophan synthase catalysed H/D exchange of the alpha-protons of amino acids. PMID- 8206267 TI - Secretion of cathepsin B and tumour invasion. PMID- 8206269 TI - Creatine kinase isoenzyme isolation from cardiac muscle. PMID- 8206270 TI - The effects of several aminopeptidases towards thionopeptides. PMID- 8206271 TI - Talin decreases the bending elasticity of actin filaments. PMID- 8206272 TI - Acid hydrolysis of Dewar isomers of bipyrimidine (6-4) photoproducts in deoxydinucleoside monophosphates. PMID- 8206273 TI - Purulent sputum as a source of neutrophil proteins. PMID- 8206274 TI - A novel matrix-degrading protease in hormone-dependent breast cancer. PMID- 8206275 TI - Collagen production in human lung fibroblasts in response to cytokines. PMID- 8206276 TI - Structure-activity relationships of para-substituted Phe analogues of [Nle10]NKA(4-10). PMID- 8206277 TI - Effect of lipopolysaccharide (LPS) on neutrophil adherence to endothelial cells. PMID- 8206278 TI - Type I and type III collagen mRNA expression in human lung fibroblasts. PMID- 8206279 TI - Interaction of HPV E6 with p53 and associated proteins. PMID- 8206280 TI - The effect of fibroblast conditioned medium on neutrophil survival and activation. PMID- 8206281 TI - Effect of the addition of protease inhibitors to sputa from cystic fibrosis patients. PMID- 8206282 TI - Resonance Raman spectroscopic studies on intact cytochrome P450 BM3. PMID- 8206283 TI - Metalloproteinase domain structure, cellular invasion and metastasis. PMID- 8206284 TI - Crystallization and biochemical characterisation of simian immunodeficiency virus proteinase mutant. PMID- 8206285 TI - Modulation of the redox properties of FMN in Desulfovibrio vulgaris flavodoxin: an investigation using site-directed mutagenesis. PMID- 8206286 TI - Preparation of the apoenzyme of the FMN-dependent Clostridium kluyveri diaphorase by extraction with apoflavodoxin. PMID- 8206287 TI - Expression and regulation of stromelysin and matrilysin by growth factors and oncogenes. PMID- 8206288 TI - Purification of glutathione S-transferase from the fungus Alternaria alternata. PMID- 8206289 TI - Torpedo marmorata gut PLY and the NPY/PP family: phylogenetic and structural considerations. PMID- 8206290 TI - Interaction analysis of various inhibitors with center n mutants of the mitochondrial cytochrome b. PMID- 8206291 TI - Investigation of the structural interactions between the myxothiazol binding and the ubiquinol oxidation sites in the bc1 complex of S. cerevisiae. PMID- 8206293 TI - Cell-adhesion molecules and metalloproteinases: a linked role in tumour cell invasiveness. PMID- 8206292 TI - Synthesis of quinolones and acridones and their inhibitory activity in NADH dehydrogenases and cytochrome b/c1-complexes. PMID- 8206294 TI - Species dependence of mitochondrial respiration inhibition by strobilurin analogues. PMID- 8206295 TI - Binding of BAS 490 F to bc1-complex from yeast. PMID- 8206296 TI - Biokinetic properties of BAS 490 F and some related compounds. PMID- 8206297 TI - Achieving biological control of phytopathogenic fungi using beta methoxyacrylates. PMID- 8206298 TI - Methoxyacrylates having oxinimo side chains. PMID- 8206299 TI - Mode of action of the new methoxyacrylate antifungal agent ICIA5504. PMID- 8206300 TI - Effect of a methoxyacrylate inhibitor on photosynthesis. PMID- 8206301 TI - Biophysical and biochemical studies of bacterial NADH:quinone oxidoreductase (NDH 1). PMID- 8206302 TI - N-alkyl pyridiniums as inhibitors of complex 1. PMID- 8206303 TI - Organotin-flavone complexes; a new class of potential biocidal compounds. PMID- 8206304 TI - Complex V of plant mitochondria--another target for agrochemicals? PMID- 8206305 TI - Glycobiology of the pentraxins. PMID- 8206306 TI - Pulsed magnetic fields affect oscillations of the adenylate cyclase enzyme system in Dictyostelium discoideum, athermally. PMID- 8206307 TI - Characterisation of the human brain serotonin 5-HT1A receptor expressed in Chinese hamster ovary cells. PMID- 8206308 TI - Expression and secretion of human protein disulphide isomerase in Saccharomyces cerevisiae. PMID- 8206309 TI - Escherichia coli and Vibrio cholerae strains deficient in an enzyme involved in disulphide bond formation (DsbA) show an increase in sensitivity to dithiothreitol. PMID- 8206310 TI - Redox-related activation and deactivation of E. coli nitrate reductase: kinetic and spectroscopic studies. PMID- 8206311 TI - A molecular dynamics study of Helix aspersa NPF. PMID- 8206312 TI - Lysine biosynthesis in plants. PMID- 8206313 TI - Sodium-dependent nucleobase transport in brush-border membrane vesicles from guinea pig kidney. PMID- 8206314 TI - Characterisation of a putative scavenger receptor for advanced glycosylation end products. PMID- 8206315 TI - Homology modelling of yeast aspartate aminotransferase. PMID- 8206316 TI - Conglutinin and CL-43, two collagenous C-type lectins (collectins) in bovine serum. PMID- 8206317 TI - Towards defining receptors for L-tyrosine and L-dopa. AB - We postulate that in mammalian systems neurotransmitter and hormone-like functions of L-tyrosine (LT) and L-DOPA (LD) are mediated via specific membrane bound and/or nuclear receptors. The structure and function of these receptors may represent an evolutionary continuum of regulatory proteins binding LT or LD in unicellular and lower multicellular organisms. PMID- 8206318 TI - Effect of cell density on androgen regulation of the mRNA level of human prostatic acid phosphatase. AB - The expression of human prostatic acid phosphatase (PAcP), a differentiation antigen of prostate epithelial cells, has been proposed to be regulated by androgen. We investigated this regulatory mechanism at the post-transcriptional level in LNCaP human prostate carcinoma cells, the only cultured cells that express PAcP. Our results demonstrated that the level of PAcP mRNA decreased when the cell density increased. Further, 5 alpha-dihydrotestosterone, an active form of the endogenous androgen, stimulated the PAcP mRNA level in low-density cells; while, caused a decrease in high-density cells. Thus, in LNCaP human prostate carcinoma cells, cell density could modulate PAcP expression at the mRNA level including androgen regulation. PMID- 8206319 TI - Effects of insulin-like growth factor II on the generation of inositol trisphosphate, diacylglycerol and cAMP in human fibroblasts. AB - In human fibroblasts, exogenous insulin-like growth factor-II (IGF-II) induce a rapid redistribution of mannose 6-phosphate/IGF-II receptors. To analyze the mechanism transducing the IGF-II signal the phosphoinositide hydrolysis, 1,2 diacyglycerol and cAMP formation were studied after incubation with IGFs. While IGF-I (10 nM, 30 s) increased the inositol trisphosphate formation IGF-II (10 nM, up to 10 min) failed to affect phosphoinositide hydrolysis and had neither an effect on basal concentrations of diacylglycerol containing arachidonic acid or myristic acid nor on intracellular cAMP. On the contrary, pretreatment with IGF II for 10 min enhanced the cAMP production stimulated by bradykinin (10 nM, 3 min) by 2.5-fold whereas no additive effects of IGF-II on the increased ligand binding to the mannose 6-phosphate/IGF-II receptor in response to bradykinin were observed. These results indicate that in fibroblasts the rapid IGF-II-induced redistribution of mannose 6-phosphate/IGF-II receptors is not mediated by inositol trisphosphate, diacylglycerol or cAMP, but that IGF-II may modulate permissively other agonist-generated signals. PMID- 8206320 TI - Non-classical receptors for aldosterone in plasma membranes from pig kidneys. AB - Rapid, nongenomic in vitro effects of aldosterone on intracellular electrolytes, cell volume and the sodium-proton antiporter have been found in human mononuclear leukocytes (HML), as have related membrane receptors. In the present study, binding of 125I-labeled aldosterone to plasma membrane preparations from pig kidneys was studied, since nongenomic in vitro effects of aldosterone have also been described in cultured kidney cells. In this preparation, binding of aldosterone shares important features with both functional and binding data in HML. These include a very low apparent Ki of approximately 0.1 nM for aldosterone, a high turnover rate and binding selectivity for aldosterone and fludrocortisone. Desoxycorticosterone acetate and corticosterone show intermediate affinity, with apparent Ki values of approximately 1 and 100 nM, with hydrocortisone even less active. Thus binding of aldosterone to kidney plasma membranes is compatible with the major features of its nongenomic renal effects. PMID- 8206321 TI - Effects of transforming growth factor-beta on human fetal adrenal steroid production. AB - Transforming growth factor-beta (TGF-beta) was found to inhibit basal and ACTH stimulated steroid production by cultured human fetal adrenal cells. The inhibitory effects of TGF-beta were both time and dose-dependent. Inhibition of basal dehydroepiandrosterone sulfate (DS) production usually was noted only after 3 or more days of treatment with > or = 0.1 ng TGF-beta/ml. The inhibitory effects of 1 ng/ml TGF-beta on ACTH-stimulated DS production were more striking than those on cortisol production by both fetal zone and neocortical cells. TGF beta also was found to interfere with DS and cortisol production by fetal zone cells in response to forskolin and dibutyryl cAMP. TGF-beta interfered with ACTH stimulation of cytochrome P450(17) alpha mRNA in fetal zone and neocortex cells. These results are suggestive that TGF-beta differentially inhibits DS and cortisol production by human fetal adrenal cells and that the site of TGF-beta action on steroidogenesis may be distal to the generation of cAMP. Such results, along with those of others, are suggestive that TGF-beta may play an autocrine/paracrine role in the human adrenal. PMID- 8206322 TI - Growth hormone induction of rat granulosa cell tissue-plasminogen activator expression and progesterone synthesis. AB - The plasminogen activator (PA) system is present in the ovary and appears to be involved both in follicular growth and ovulation. Similarly, the growth hormone (GH) has been demonstrated to positively affect some ovarian activities. Interestingly, GH appears not only as a mediator of gonadotropin effects, but also as having an independent action of its own on the ovary. In the present study we wanted to investigate if GH could affect ovarian plasminogen activator (PA) activity and steroidogenesis. Granulosa cells from immature rats, injected with pregnant mare serum gonadotropin (PMSG) for inducing follicular growth, were cultured for 24 h with increasing concentrations of GH. A significant dose dependent increase in tPA activity was observed in the GH-treated cells. This effect was exerted at the mRNA level and the use of cycloheximide, a protein synthesis inhibitor, suggested that GH did not require any other intermediary protein for inducing tPA-mRNA. Furthermore, cAMP levels were not affected by GH treatment. Finally, GH was found to increase progesterone (P) synthesis by granulosa cells. The correlation between the PA system and ovulation and the importance of a normal steroidogenesis for the ovarian physiology claim for a key role of GH in the ovarian activities. PMID- 8206323 TI - Compartmentalization of type I 17 beta-hydroxysteroid oxidoreductase in the human ovary. AB - The steroid-metabolizing enzyme, type I 17 beta-hydroxysteroid oxidoreductase (17 beta-HSOR) also called 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) plays a key role in ovarian synthesis of 17 beta-estradiol. This is the only enzyme in the steroid-metabolizing pathway which has not been localized in the human ovary by immunohistochemistry. In this study, using antibody directed against human placental cytosolic 17 beta-HSOR (type I), a single protein band with a relative molecular mass of approximately 34 kDa was demonstrated by Western analysis in both human luteinized granulosa cells and placental tissue. In placental tissue, immunoreactive type I 17 beta-HSOR was demonstrated within the syncytiotrophoblast using immunohistochemistry. In human ovary, immunoreactive type I 17 beta-HSOR was localized exclusively in granulosa cells of developing follicles, ranging from primary follicles with a single layer of cuboidal-shaped granulosa cells, preantral follicles with multiple layers of granulosa cells, and large antral follicles. No immunoreactivity was detected in spindle-shaped granulosa cells of primordial follicles, theca interna, theca externa or surrounding stroma. In the corpus luteum, type I 17 beta-HSOR immunoreactivity was localized solely in granulosa-lutein cells. For comparison, immunoreactive 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) was examined in the same tissues. Both theca interna and granulosa cells of preantral and antral follicles exhibited 3 beta-HSD staining. Primary follicles did not exhibit detectable 3 beta-HSD in either granulosa or theca cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206324 TI - Expression of guanine-nucleotide-binding proteins in lean and obese insulin resistant mice. AB - To examine whether G protein were affected in the obese insulin-resistant state, the level of various G proteins (alpha i1, alpha i2, alpha i3, alpha o and alpha s) was assessed by immunodetection in lean and experimentally induced obese mice. Crude membranes were prepared from adipose tissues, muscle, liver, kidney and brain. G alpha-subunits were similar in lean and obese animals in brain, kidney, skeletal or heart muscle. Hepatic G alpha s, G alpha i2 and G alpha i3 subunits were markedly elevated in obese mice. When total tissue contents were considered, interscapular brown adipose tissue and epididymal fat pads from obese animals contained more alpha i2 than the lean tissues, while alpha i1, alpha i3 and alpha s were similar in both groups. However, when expressed per mg of membrane protein, alpha i1, alpha i3 and alpha s were decreased and alpha i2 was normal in white adipose tissue of obese animals. Thus the expression of the G protein alpha subunits seems to be regulated by tissue-specific factors rather than by circulating factors. PMID- 8206325 TI - Evidence for transcriptional inhibition of GnRH gene expression by phorbol ester at a proximal promoter region. AB - We previously showed that activation of protein kinase C (PKC) with the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) in GT1-7 hypothalamic cells decreases GnRH mRNA levels in a dose and time dependent fashion. In the present studies, we examined the mechanism of this effect. Analysis of the half-life of GnRH mRNA levels after transcriptional arrest with actinomycin-D (5 micrograms/ml) estimated the half-life of GnRH mRNA to be 22 h. TPA treatment did not alter the GnRH mRNA half-life directly, suggesting that the effects of TPA occur predominantly at the level of gene transcription. Exposure of cells transiently transfected with various deletion constructs of the rat (r)GnRH promoter to TPA resulted in a decrease of 60% in luciferase reporter activity. This repression was maintained in constructs deleted to position -126 and was lost with further deletion to position -73. In conclusion, these experiments suggest that phorbol esters repress GnRH expression at the level of transcription through DNA sequences in the proximal rGnRH promoter. PMID- 8206326 TI - DNA topology regulates rat prolactin gene transcription. AB - A cell-free transcription system was used to examine the effects of DNA negative supercoiling on transcription from rat prolactin promoters. The mRNA was faithfully transcribed from prolactin promoters that contained the DNA fragment spanning from -1960 to -10 base pairs upstream of the prolactin transcription start site. Prolactin promoters in supercoiled form, prepared from Escherichia coli, have a higher transcriptional efficiency than the promoter in the relaxed form. Deletion of DNA sequences containing the estrogen response element and putative non-B form DNA elements from the upstream region of the prolactin gene did not alter this effect of DNA topology on prolactin transcription. We further separated transcription into preinitiation and elongation steps by using sarkosyl and found that more preinitiation complexes were assembled on the supercoiled prolactin promoters than on the relaxed promoters. DNA supercoiling therefore plays an important role in controlling prolactin gene expression by facilitating the formation of preinitiation complexes on the promoters. PMID- 8206327 TI - Activity of growth hormone peptides bGH 96-133 and hGH 95-133 in 3T3-F442A cells. AB - Chemically synthesized bovine growth hormone (bGH) bGH 96-133 and its human homologue, hGH 95-133, have similar in vitro biological activities. Unlike native GH, bGH 96-133 and hGH 95-133 were completely without adipogenic or anti-insulin activity at doses up to 10 microM. bGH 96-133 had insulin-like activity, with a 100% increase in glucose uptake at 10 microM. bGH was anti-mitogenic and bGH 96 133 and hGH 95-133 were mitogenic (EC50 approximately 180 nM and maximal response at 1-2 microM). Only bGH 96-133 and hGH 95-133 displaced [125I]hGH 95-133 binding from 3T3-F442A fibroblasts with a Kd between 60-120 nM. bGH, hGH, insulin and IGF I were without effect on [125I]hGH 95-133 binding. bGH 96-133 and hGH 95-133 did not significantly inhibit [125I]hGH or [125I]IGF-I binding. These experiments indicate that GH containing peptides bGH 96-133 and hGH 95-133 have mitogenic and insulin-like activity without the adipogenic, anti-insulin or anti-mitogenic activity of bGH. These peptides have a specific binding site which appears to be distinct from the GH, insulin and IGF-I receptors. PMID- 8206328 TI - Topographical differences in human choriogonadotropin antagonist as revealed by monoclonal antibodies. AB - Human choriogonadotropin (hCG), a highly glycosylated hormone loses its biological activity following deglycosylation. The deglycosylated hormone (DG hCG) binds to gonadal cell receptors without causing complete signal transduction. In order to analyze the molecular features of DG-hCG, we have prepared and studied five monoclonal antibodies (Mab). Two DG-hCG Mabs were highly specific while three others showed some but low cross-reactivity with hCG. Only those that recognized hCG albeit weakly, could inhibit binding of 125I-hCG to receptors or hCG action in MA-10 (mouse Leydig tumor cells). All five Mabs were highly reactive with the free alpha subunit. As these alpha subunit favoring antibodies easily recognized DG-hCG but not the intact hCG configuration, we suggest that loss of sugars in alpha and beta subunits of DG-hCG was responsible for these alterations. Thus, in the molecular topography of DG-hCG, the orientation of the alpha subunit would be different from that in the native hormone and this may be further perturbed following binding to the specific receptor, leading to inefficient coupling to the signal transducing machinery. PMID- 8206329 TI - Processing of insulin-like growth factor-II (IGF-II) by human breast cancer cells. AB - MCF-7 cells transfected with human prepro-IGF-II cDNA secreted two large precursor forms of 22 and 15 kDa, with trace amounts of the mature 7 kDa IGF-II, suggesting that overexpression leads to saturation of processing and the secretion of precursors. The 15 kDa form was separated from 22 and 7 kDa IGF-II by cation-exchange chromatography. Intracellular IGF-II, detectable only in detergent buffers, existed in two forms of 24 and 22 kDa. Conditioned media from four other breast cancer cell lines (MDA-231, HBL-100, T47D and MCF-7 McG), all contained mature 7 kDa IGF-II with trace amounts (< 10%) of the 15 kDa IGF-II. Oestradiol induced IGF-II secretion in oestrogen-sensitive MCF-7 and T47D cells, but secretion was constitutively higher in oestrogen-unresponsive MDA-231 and HBL 100 cells. This indicates, for the first time, that oestrogen regulation of IGF II peptide in breast cancer cells, and expression throughout all cell lines tested, would support the hypothesis that IGF-II has an autocrine regulatory function in breast cancer. PMID- 8206330 TI - Endocytosis and degradation of prolactin and its receptor in Chinese hamster ovary cells stably transfected with prolactin receptor cDNA. AB - Molecular cloning of the prolactin (PRL) receptor cDNA has revealed different forms of the receptor: among them, the longest form encodes a transmembrane protein of 592-598 amino acids and was originally found in rabbit mammary gland as well as in human and rat tissues. It contains a cytoplasmic domain of 358 amino acids. In CHO cells transfected with the PRL receptor cDNA, PRL is able to induce the specific expression of a reporter gene provided with the promoter of the milk protein gene beta-lactoglobulin. The cDNA encoding this long receptor form has been expressed permanently after stable transfection of Chinese hamster ovary (CHO) cells. In these cells, we have determined the fate of the bound hormone and of the receptor. At 37 degrees C, transfected cells were able to endocytose 125I-labeled human growth hormone (hGH) or ovine prolactin (oPRL) at an initial rate of about 1 fmol/h at 100 pM labeled hormone and 10(6) cells/well. Lowering the temperature to 15 degrees C slowed the endocytosis of [125I]hGH by a factor of 5. These results were confirmed by electron microscopy with oPRL labeled with colloidal gold. At 37 degrees C, the receptor underwent rapid insertion to the cell surface and constitutive endocytosis (half-life 80 min). This rate of endocytosis was enhanced in the presence of 10 nM oPRL (half-life 8 min), leading to down-regulation of the receptor by exhaustion of the intracellular receptor pool. After down-regulation, the cell surface was replenished with newly synthesized PRL receptor with a half-time of 8-10 min. If cycloheximide was added, almost no receptors could be found on the cell surface. These results indicate that in transfected cells the PRL receptor behaved largely as in classical target cells. A "conveyor belt" endocytosis behavior was found, with degradation of the endocytosed receptors, and occupation by the hormone enhancing this process. Moreover, since the PRL receptor belongs to a family of receptors in which companion protein(s) seem to play important roles, transfected CHO cells appear to provide the expressed receptors with the necessary element(s) to function as in normal PRL target cells. PMID- 8206331 TI - 12-O-tetradecanoyl-phorbol-13-acetate (TPA) counteracts the cAMP up-regulation of the expression of the stimulatory guanine nucleotide binding protein (Gs alpha) and Gs alpha messenger RNA in cultured pig thyroid cells. AB - In this study, we examined whether the protein kinase C (PKC) pathway could interfere with the regulation of Gs protein in porcine thyroid cells. The two days culture of cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) (0.1 microM) alone neither affected adenylyl cyclase activity, nor the level of Gs alpha protein in membranes when compared with control cells. The co-addition of TPA with thyrotropin (TSH) (1 mU/ml) or forskolin (fk) (10 microM) in the culture medium, abolished the stimulatory effects of either agonists on the activation of adenylyl cyclase by fk or [AlF4]- and on the increase of Gs alpha protein. By contrast, TPA had effects neither on the Gi-dependent inhibition of adenylyl cyclase nor on Gi alpha proteins levels. The level of Gs alpha mRNA measured by Northern blot analysis was increased (200%) in TSH- or fk-treated cells and this increase was counteracted by TPA. The effects of TPA observed after 6-9 h of contact with cells were mimicked by mezerezin, a non-phorbol protein kinase C activator and blocked by bisindolylmaleimide a specific protein kinase C inhibitor (GF 109203X). These results suggest that the activation of the PKC pathway prevents the cAMP-dependent up-regulation of Gs alpha protein and Gs alpha mRNA expression. PMID- 8206332 TI - The human myometrial CRH receptor: G proteins and second messengers. AB - The initiation of human parturition remains an enigma but is thought to involve a number of hormonal signals such as oxytocin and prostaglandins. One other possible signal is placentally derived corticotropin-releasing hormone (CRH). We have recently reported that the human myometrium expresses a specific receptor for CRH which changes to a high affinity state prior to term. In view of this we sought to determine whether this receptor is functionally linked to some of the known modulators of myometrial function. Myometrial membranes were prepared by differential centrifugation from either pregnant (caesarian section) or non pregnant (hysterectomy) myometrium. For binding studies the membranes were incubated with radiolabelled oCRH at 22 degrees C for 2 h. For second messenger studies they were incubated at 37 degrees C for 10 or 30 min with either 0.5 mM ATP and 10 mM theophylline (cAMP) or 0.05 mM arachidonic acid or 0.5 mM linoleic acid (PGE2). When increasing concentrations of membranes were incubated with radiolabelled oCRH an interesting phenomenon was observed. In non-pregnant membranes the binding reached a plateau, whereas in membranes prepared from pregnant myometrium, the binding decreased at concentrations above 130 micrograms/ml. Possible explanations for this phenomenon include an inhibitor which prevents ligand-receptor binding or an enzyme which destroys the receptor binding region of the ligand. Incubation of both types of membranes with GTP or its analogue, GppNHp, resulted in a dose-dependent inhibition of specific binding suggesting that the myometrial CRH receptor is linked to a G regulatory protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206333 TI - Agonist-antagonist activity of anti-estrogens in the human breast cancer cell line MCF-7: an hypothesis for the interaction with a site distinct from the estrogen binding site. AB - Non-steroidal anti-estrogens exhibit an extremely complex pharmacology because of their estrogenic and anti-estrogenic effects in different species. Recently, we have reported evidence for an immunochemical difference in the estrogen receptor (ER) when it is occupied with anti-estrogens as compared to estrogens (Martin et al., 1988). In this study, we have compared immunoreactivity of MCF-7 cell estrogen receptor when bound to anti-estrogen versus estrogen. We show that the occupation of ER with antiproliferative concentrations of various anti-estrogens leads to the appearance of additional antigenic determinants for the H222 monoclonal anti-estrogen receptor antibody. When performing ER immunoassay after sedimentation of estrogen receptors on sucrose gradients, we show that exposure of new epitopes induced by anti-estrogens can occur on a 4 s molecular form related to the 66 kDa monomeric estrogen receptor. Also, when ER are previously occupied by estradiol, the addition of low anti-estrogen concentrations, which are unable to displace estradiol from the estrogen receptor, leads to a significant increase of H222 epitopes. Our results led us to propose a molecular model for anti-estrogen-receptor interaction in which their dual agonist/antagonist activity may be due to the occupation of distinct binding sites on the estrogen receptor. PMID- 8206334 TI - Follicle-stimulating hormone regulation of AP-1: inhibition of c-jun and stimulation of jun-B gene transcription in the rat Sertoli cell. AB - The proto-oncogenes c-fos and c-jun and the related jun-B encode the components of transcription factor, AP-1, a heterodimeric DNA-binding protein that mediates hormone and growth factor-regulated gene expression. In the rat Sertoli cell, FSH rapidly inhibited c-jun gene expression while it stimulated c-fos and jun-B as well as the expression of the more slowly responding, tissue plasminogen activator (tPA) and inhibin alpha-subunit. These early effects of FSH were not inhibited by cycloheximide. Nuclear run-off analyses demonstrated that the FSH dependent decline in c-jun and increases in c-fos, jun-B, tPA and inhibin alpha subunit mRNAs were regulated at the transcriptional level. The rates of degradation of c-fos, c-jun and jun-B mRNAs were unaffected by FSH while tPA and inhibin alpha-subunit mRNAs were stabilized. After 8 h of FSH treatment, the transcription of all five genes returned to basal rates. These data demonstrate immediate-early regulation by FSH of the expression of genes encoding components of the transcription factor, AP-1. PMID- 8206336 TI - Negative and positive regulation of IGF-II mRNA expression in cultured rat cells by chicken serum. AB - We have investigated the possibility that some serum factors might negatively regulate the expression of the insulin-like growth factor-II (IGF-II) gene in 18 54, SF cells. Northern blot analyses indicated that there were three major transcripts (3.8 kb, 1.8 kb, and 1.2 kb) of the IGF-II gene in these cells. We found that incubation of 18-54, SF cells in medium containing very high concentrations (50-100%) of chicken serum greatly inhibited the steady-state level of all three IGF-II mRNA species. In addition, we also found that incubation of 18-54, SF cells in medium containing lower concentrations (10-50%) of chicken serum induced a 3.5 kb IGF-II mRNA. The inhibitory effect of high concentrations of chicken serum on IGF-II mRNA expression was not due to a cytotoxic effect of the serum, because these cells were maintained in 100% chicken serum for up to two weeks without loss of cell viability. The inhibitory effect of chicken serum on IGF-II mRNA was reversible after withdrawal of the serum. Nuclear run-on assays suggested that this negative regulation of IGF-II mRNA in 18-54, SF cells by chicken serum was not the result of transcriptional inhibition. Treatment of 18-54, SF cells that had been previously incubated in 100% chicken serum for 24 h with actinomycin D resulted in a partial restoration of the expression of the 3.8 kb and 1.2 kb IGF-II mRNA in these cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206335 TI - Calcitonin receptor in human placental syncytiotrophoblast brush border and basal plasma membranes. AB - The physiology of calcium transport through the placenta has not been studied thoroughly. In particular, the effect of calcaemic hormones on this process has never been reported. In this paper we questioned if calcitonin, a hypocalcaemic hormone, is also implicated in the regulation of calcium transport by one of the placental syncytiotrophoblast bipolar membranes. In order to investigate the implication of calcitonin on calcium transport, we first studied whether this hormone binds to any of these bipolar membranes, i.e. purified syncytiotrophoblast brush border (facing the mother) and basal plasma membranes (facing the fetus). The initiation of binding of human [125I]calcitonin to the two types of membranes was rapid and reached a steady state after 10 min of incubation at 37 degrees C. The number of binding sites and the affinity of these receptors for the hormone were studied for each type of membrane, with concentrations of [125I]calcitonin varying from 0.01 to 1.8 nM. Scatchard analysis revealed a single affinity binding site for human calcitonin with Kds of 0.83 +/- 0.09 nM and 0.67 +/- 0.26 nM for brush border and basal plasma membranes respectively. The maximal number of receptors was significantly different (p < 0.001) in the two membranes: Bmax of 66.64 +/- 9.15 fmol/mg protein for brush border membranes and 19.66 +/- 2.80 fmol/mg protein for basal plasma membranes. Competitive displacement of [125I]calcitonin with other ligands showed the following potencies between human calcitonin > salmon calcitonin > calcitonin gene-related peptides and segments analogues but no competition with some human calcitonin gene-related peptides fragments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206337 TI - Preparative purification of phosphorylated and nonphosphorylated bovine prolactins. AB - Extracts from 12 pituitaries were applied to preparative immunoaffinity chromatography columns containing between 500 mg and 800 mg of clonal antiprolactin IgG1. Extracts were cycled through the column and subsequently washed from the affinity matrix. Total prolactin was eluted from the affinity matrix by a 0.1 M glycine, pH 2.8. The total prolactin was neutralized and dialyzed into 20 mM Bis-Tris (pH 7.0) and applied to a weak anion exchange column. Nonphosphorylated prolactin was eluted with 0.5 M NaCl in Bis-Tris buffer. Phosphorylated prolactin was eluted with 20% acetic acid. Yields averaged 19.6 mg and 11.7 mg for native and phosphorylated prolactin (n = 14 runs), respectively. The molecular weights of the prolactins were similar to prolactin standards. The amino acid compositions of the two prolactin variants were similar. Phosphate was associated predominantly with the phosphorylated prolactin. Native prolactin was biologically active in the Nb2 rat lymphoma bioassay, while the phosphorylated prolactin was without activity in this bioassay. PMID- 8206338 TI - Expression of PC2 and PC1/PC3 in human pheochromocytomas. AB - Expressions of two Kex2-related proteases, Pc2 and PC1/PC3, and of one of their possible substrates, proenkephalin, were examined in normal (n = 7) and various pathological (n = 48) human adrenal tissues. Northern blot analysis detected the expression of these genes in pheochromocytomas only. In the 20 pheochromocytomas studied with this technique, PC2, PC1/PC3 and proenkephalin were expressed in 85%, 50% and 90%, respectively. The presence of PC2 and PC1/PC3 was further confirmed using the sensitive RT/PCR techniques. Other evidence of human tumoral adrenal medullary PC2 expression was provided by in situ hybridization and immunohistochemistry. In addition, proenkephalin was expressed only in the pheochromocytomas expressing PC2 and/or PC1/PC3. These results demonstrate that functional Kex2-related endoproteases are expressed in human pheochromocytomas and may be involved in the processing of proenkephalin. PMID- 8206339 TI - Calcium regulates stanniocalcin mRNA levels in primary cultured rainbow trout corpuscles of stannius. AB - Stanniocalcin (STC) is an inhibitor of gill calcium transport produced by the corpuscles of Stannius (CS), endocrine glands in bony fishes. In previous studies we have described how STC secretion is regulated by calcium both in vitro and in vivo, using rainbow trout as a model system. In this report we have examined the effects of calcium on STC mRNA levels in primary cultured trout CS cells. The results show that message levels are positively regulated by extracellular calcium concentrations within the physiological range. The calcium response was also temporally-related as more prolonged exposures tended to have greater effects. Similar concentrations of magnesium had no effect on message levels. This represents another level at which calcium regulates the CS cell, in addition to its established effects on STC synthesis and secretion. The results are discussed in relation to the other known calciotropic hormones, calcitonin and parathyroid hormone. PMID- 8206340 TI - [The immunobiochemical composition of the cerebrospinal fluid in patients with optochiasmic arachnoiditis under the action of therapeutic electrostimulation of the optic nerves]. PMID- 8206341 TI - [Immunological disorders in the population of Kursk Province 6 years after the Chernobyl catastrophe and the means for their correction]. PMID- 8206342 TI - [The autonomic and psychoemotional status of young schoolchildren from regions with radionuclide contamination of the area]. PMID- 8206343 TI - [The characteristics of lipid metabolism in permanent residents of the North]. PMID- 8206344 TI - [The development of the immune response in healthy persons adapting to unusual climatic and geographic conditions]. PMID- 8206345 TI - [The status of the lipid peroxidation-antioxidant system in young men on moving to a region in the Far East]. PMID- 8206346 TI - [The mechanical properties of human skin. I]. PMID- 8206347 TI - [Respiratory indices and their relation to individual tolerance for the passive orthostatic test]. PMID- 8206348 TI - [Changes in the wave structure of the cardiac rhythm during information loading]. PMID- 8206349 TI - [Monthly fluctuations of the individual minute in women]. PMID- 8206350 TI - [Hemispheric specialization in the recognition of visual information]. PMID- 8206351 TI - [A structural analysis of the factors in adaptation to an occupational environment in semiautomated production]. PMID- 8206352 TI - [An evaluation of the attitude of the human operator to the extreme situations of his work]. PMID- 8206353 TI - [The quality of the activity of a human operator and the physiological shifts in acute alcoholic intoxication]. PMID- 8206354 TI - [The characteristics of the manifestation of the basic psychophysiological law during human work in a biofeedback regimen]. PMID- 8206355 TI - [The use of cerebral and systemic blood flow parameters and the respiratory pattern for characterizing the physiological costs of activity]. PMID- 8206356 TI - [A psychophysiological analysis of the subjective intensity of physical loading]. PMID- 8206357 TI - [The structure of the hemodynamic reactions to isometric loading in relation to the initial arterial pressure level]. PMID- 8206358 TI - [The development of work power during strength training]. PMID- 8206359 TI - [Functional asymmetry of the surface muscles of the spine in persons of different ages during physical education exercises and in pains in the area of the backbone]. PMID- 8206360 TI - [The quantitative analysis of time-patterned finger tapping]. PMID- 8206361 TI - [The relative role of the monosynaptic and polysynaptic pathways in alpha-motor neuron recruitment in the tonic vibration reflex]. PMID- 8206362 TI - Population dynamics of DNA fingerprint patterns within and between populations. AB - DNA fingerprint is a pattern of a variable number of bands (DNA fragments) with different sizes on a Southern gel for each individual, generated by one or many VNTR loci. Genetic divergence between individuals within and between populations can be studied in terms of number of shared bands between individuals. Using a population genetic model we show that the expectations of measures of genetic distance between populations based on band sharing data from DNA fingerprint patterns are functions of composite parameters M = 4Nv, and time of divergence (t) between populations, where N is the effective size of the populations, and v, the mutation rate. The expected genetic distance remains linear with time of divergence at least up to N generations as long as the average heterozygosity at the DNA fingerprint loci remains at or below 90%. Neither incomplete knowledge of the allele frequencies at each locus, nor the unknown number of loci underlying DNA fingerprint pattern, compromise these evolutionary dynamics of DNA fingerprint patterns. Applications of this theory to data on three human populations, and review of literature indicate that co-migration of alleles, and the presence of syntenic loci underlying the fingerprint pattern have little impact of the reliability of evolutionary conclusions from DNA fingerprint studies. PMID- 8206363 TI - Genetic basis and evolution of species-specific courtship song in the Drosophila auraria complex. AB - The interpulse interval (IPI) of courtship song in the Drosophila auraria complex is the only parameter that is consistently species-specific among the several courtship elements examined within the complex. The genetic basis of the species specific courtship song was examined by analysing the song of interspecific hybrids and of backcross progeny. IPI of all interspecific hybrids except two showed intermediate values, suggesting autosomal control of species-specific IPI. However, significant deviation for shorter IPI from midparent was found in thirteen out of 20 crosses. The chromosomal analysis between D. auraria and D. biauraria revealed that the two major autosomes had significantly large effects on IPI, but the sex chromosome and cytoplasm had no effect. Since no interaction was detected, it is concluded that each autosome acts additively in the determination of species-specific IPI. The common ancestors of the D. auraria complex may also have had autosomal control of IPI, which has been conserved during speciation in the complex. PMID- 8206364 TI - The molecular basis of instability of the singed(very weak) mutation in Drosophila melanogaster. AB - The singed(very weak) mutation was created by the sequential addition of two P transposable elements to the singed gene. The mutation can be somatically unstable through the action of a dominant maternal effect mutation on the second chromosome. It is also unstable in the germ line in these conditions. Sequencing of the region of the P insertions in the mutation reveals that the two inserted elements have single internal deletions, and the larger of the two is a copy of the KP element. The mutation will generate, at high frequencies, strongly singed and pseudo-wild type products by reversions occurred in the germline. These are the result of the precise excision of the smaller and the larger elements respectively. By PCR amplification of dissected thoraces we show that the somatic instability of the mutation, from a weak to a strong singed phenotype, is also caused by the excision of the smaller of the two elements. PMID- 8206365 TI - Differences in P element population dynamics between the sibling species Drosophila melanogaster and Drosophila simulans. AB - Patterns of P element establishment and evolution were compared in populations of D. melanogaster and D. simulans. For each species, mixed populations were initiated with M strain flies lacking P elements together with P strain flies having similar P element copy numbers and phenotypes. The mixed populations were subsequently maintained under similar environmental conditions. On the basis of gonadal sterility assays, P elements tended to be significantly more active in D. melanogaster than in D. simulans populations. This activity difference between the two species was positively associated with P element copy number, determined by restriction enzyme analysis, and transposition frequency, as determined by a transposition assay. Host factors are the most likely explanation for the observed species variation. Difficulty of establishment may be a factor determining the absence of P elements in natural populations of D. simulans. PMID- 8206366 TI - Simulation of marker assisted selection in hybrid populations. AB - A computer model is developed that simulates Marker Assisted Selection (MAS) in a population produced by a cross between two inbred lines. Selection is based on an index that incorporates both phenotypic and molecular information. Molecular markers contributing to the index and their relative weights are determined by multiple regression of individual phenotype on the markers. The model is applied to investigate the efficiency of MAS as affected by several factors including total number of markers in the genome, number of markers contributing to the index, population size and heritability of the character. It is demonstrated that selection based on genetic markers can effectively utilize the linkage disequilibrium between genetic markers and QTLs created by crossing inbred lines. Selection is more efficient if markers contributing to the index are re-evaluated each generation than if they are evaluated only once. Increasing the total number of markers in the genome as well as the number of markers contributing to the index does not necessarily result in a higher efficiency of selection. Moreover, too many markers may result in a weaker response to selection. Population size is shown to be the most important factor affecting the efficiency of MAS. PMID- 8206367 TI - Effects of autosomal inversions on meiotic exchange in distal and proximal regions of the X chromosome in a natural population of Drosophila melanogaster. AB - We have investigated the interchromosomal effect of the naturally-occurring paracentric inversions In(2L)t and In(3R)P on meiotic recombination in two regions of the X chromosome in Drosophila melanogaster. Previous authors have suggested that the rate of recombination at the tip of the X chromosome may be substantially higher in some natural populations than values measured in the laboratory, due to the interchromosomal effect of heterozygous autosomal inversions. This suggestion was motivated by observations that transposable elements are not as common at the tip of the X chromosome as predicted by recent research relating reduced meiotic exchange to increased element abundance in D. melanogaster. We examined the effects of heterozygous In(2L)t and In(3R)P on recombination at both the tip and base of the X chromosome on a background of isogenic major chromosomes from a natural population. Both inversions substantially increased the rate of recombination at the base; neither one affected recombination at the tip. The results suggest that the presence of inversions in the study population does not elevate rates of crossing over at the tip of the X chromosome. The relevance of these results to ideas relating transposable element abundance to recombination rates is discussed. PMID- 8206368 TI - Regional specificity of HTLV-I proviral integration in the human genome. AB - The location of HTLV-I (human T-cell leukemia virus type 1) proviral sequences in the genome of infected human cells was explored by hybridization of a viral probe with compositional fractions of host-cell DNAs. In the twelve cases examined, HTLV-I sequences were absent from the GC-poorest 40% of the host genome (namely, from isochores that are below 39% GC). Transcriptionally inactive proviral sequences were localized in GC-poor isochores (comprised between 39% and 42-44% GC) of the human genome, which are characterized by a constant and low gene concentration. In contrast, transcriptionally active proviral sequences were found in the GC-rich and very GC-rich isochores, which are gene rich, transcriptionally and recombinationally active, and endowed with an open chromatin structure. Since GC-rich isochores are present in R'-bands and very GC rich isochores form T-bands, these results also provide information on the location of HTLV-I proviral sequences in human chromosomes. The results obtained with HTLV-I are in agreement with the non-random, compartmentalized integration of animal retroviral sequences that had been previously observed in other viral host systems. They provide, however, much more detailed information on the regional location of proviral sequences in the host genome and on the correlation between their transcription and their location. PMID- 8206369 TI - Cloning and growth-regulated expression of the gene encoding the hepatitis B virus middle surface antigen in Yarrowia lipolytica. AB - Expression of the gene encoding the hepatitis B virus middle surface antigen (pre HBsAg) in the yeast Yarrowia lipolytica has been studied. The preS2-HBsAg gene was expressed from the alkaline extracellular protease-encoding gene (XPR2) promoter. In the fusion construct, the membrane-spanning 'a' domain of preS2 HBsAg has been replaced by the leader peptide and the proI region of the alkaline protease, thus eliminating the epitope responsible for the immune escape mechanism. Expression has been found to be growth-stage dependent with the highest protein accumulation during the stationary phase, accounting for around 2.35% of the total soluble intracellular proteins. The produced protein was assembled into Dane particles and was immunogenic in mice. The expression vector was found to be stable for at least 100 generations under non-selective conditions. PMID- 8206370 TI - RNA- and single-stranded DNA-binding (SSB) proteins expressed during Drosophila melanogaster oogenesis: a homolog of bacterial and eukaryotic mitochondrial SSBs. AB - Little is known about the identity and involvement of single-stranded (ss) DNA binding (SSB) and RNA-binding proteins in developmental processes that occur during oogenesis in Drosophila melanogaster (Dm). Here, we describe a molecular approach designed to identify such proteins by virtue of their ssDNA-binding activity. We have constructed a directional ovarian cDNA library and conducted expression cloning screens which identified five unique cDNAs that encode proteins capable of binding ssDNA. All five represent previously unreported sequences. The remainder of this paper focuses on one of these cDNAs which encodes a Dm protein displaying significant sequence homology to Escherichia coli ssDNA-binding protein (SSB, involved in DNA replication, repair and recombination), as well as eukaryotic SSBs isolated from the mitochondria (mt) of rats, frogs, humans and yeast. The deduced amino acid (aa) sequence of this 15.6 kDa protein, which we will refer to as Dm mtSSB, displays average identities of 38.3% with eukaryotic mtSSBs and 23.4% with bacterial SSBs. Gel retardation analysis with an affinity-purified GST fusion protein confirms that Dm mtSSB specifically binds ss, but not double stranded DNA. Dm mtSSB is encoded by a nuclear gene whose expression appears to be developmentally regulated. It is expressed as a single 600-nucleotide (nt) transcript during oogenesis and embryogenesis. A larger transcript of 1500 nt is prevalent in some later stages of Dm development. PMID- 8206371 TI - Structural and functional divergences of the columbid annexin I-encoding cp37 and cp35 genes. AB - Annexin-I proteins in the pigeon are encoded by two genes. One encodes a constitutively expressed cp37 protein, and the other encodes a major prolactin (PRL)-regulated protein (cp35). As one goal in understanding the differential regulation of these genes, we have determined a 10.8-kb genomic sequence of the cp37 gene containing 1.3 kb of 5'-flanking region and the first six exons. The promoters of cp37 and cp35 are 84% identical over the first 210 bp upstream from the transcription start point (tsp). Cell-free transcription demonstrated that this -210 region of cp37 contained an active promoter. Two nuclear protein binding sites, which may be involved in the constitutive expression of cp37, were localized between -205 and -106 bp. PRL-dependent transcription factors bind to the -73 to -8 region of cp35, but not cp37. The sequences of these regions contain six single-base differences, which may be responsible for the genes' divergent transcriptional regulation. The 5'-flanking regions of cp37 and cp35 were cloned into a reporter plasmid and transfected into T-47D cells. Transient transfection analysis revealed that the constructs containing cp35 5'-flanking regions were inactive, whereas the cp37 promoter was constitutively active and contained both positive and negative cis-acting sequences. PMID- 8206372 TI - A single point mutation results in A allele-specific exon skipping in the bovine alpha s1-casein mRNA. AB - Bovine alpha s1-casein (alpha s1-CN) allele A is found in low allelic frequencies among different cattle breeds and is known to be characterized by the deletion of amino-acid residues 14 to 26 of the mature protein (as defined via the most common allele B), and a corresponding deletion of 39 bp from its cDNA. Based upon the genomic sequence of bovine alpha s1-CN [Koczan et al., Nucleic Acids Res. 19 (1991) 5591-5596], this allelic deviation can be interpreted as an absence of exon 4 from the A allele mRNA and protein product. We demonstrate that this allelic aberration is not caused by a genomic deletion across the exon-4 DNA, but is correlated with a single point mutation at position +6 in the splice donor sequence distal of exon 4, which results in upstream exon skipping during the serial splice reactions of the A allele alpha s1-CN pre-mRNA. The A-allele specific mutation at position +6 is able to interrupt the perfect complementarity of the intron-4 splice donor signal (positions one to eight) with U1-snRNA, which may then no longer be able to compensate for a rather weak exon-4 upstream splice acceptor sequence in facilitating the initial binding of U2 auxiliary factor/65 kDa (U2AF65) to that polypyrimidine tract. This interpretation of the exon skipping mechanism in alpha s1-CN allele A is in agreement with similar results obtained [Hoffmann and Grabowski, Genes Dev. 6 (1992) 2554-2568] in an analysis of the rat preprotachykinin-encoding gene and in vitro experiments. PMID- 8206373 TI - A highly conserved region in the hormone-binding domain of the human estrogen receptor functions as an efficient transactivation domain in yeast. AB - Human estrogen receptor (hER) mutants which activate transcription in the absence of hormone were isolated by random mutagenesis and genetic selection in the yeast Saccharomyces cerevisiae. Twenty constitutive hER mutants defining ten different alleles were selected. All sequence changes resulted in truncations of the receptor within a 123-amino-acid (aa) segment (aa 270 to 393) spanning the D region and the N-terminal part of region E which contains the hormone-binding domain (HBD). Transactivation assays using both the constitutive hER mutants and a series of deleted receptor derivatives generated in vitro revealed that the N terminal part of region E, between aa 302 and 339, contains an efficient transcriptional activation function which is constitutively active in yeast. The location of this transactivation function in hER is similar to that of the tau 2 activation function of the glucocorticoid receptor and corresponds to a sequence which is highly conserved among the steroid hormone receptors. Thus, a conserved region exists in the HBD of the hER which can function as an autonomous transactivation domain. PMID- 8206374 TI - Translational regulation of a recombinant operon containing human platelet derived growth factor (PDGF)-encoding genes in Escherichia coli: genetic titration of the peptide chains of the heterodimer AB. AB - A new strategy is described for the production of recombinant heteromultimeric proteins using Escherichia coli as host. A recombinant operon was constructed containing modified cDNA sequences encoding the mature A and B chains of human platelet-derived growth factor (PDGF). The relative expression rates of the PDGF genes were varied over a range equivalent to A:B ratios from 0.8 to 3.7 by means of translational regulation. This was achieved using two different translational initiation sequences (TIS) upstream from the respective coding regions, one derived from the E. coli atpE translational initiation region, and the other containing a sequence with extended complementarity to the 3' end of the 16S rRNA. The generation of mature PDGF A and B chains in different relative amounts in E. coli provided the basis for developing a novel procedure for the production of the biologically active PDGF heterodimer AB in large quantities. The general strategy is applicable to the preparation of a wide range of heteromultimeric complexes. Moreover, the described PDGF operon constitutes a compact and versatile model system for studies of the posttranscriptional regulation of gene expression. PMID- 8206375 TI - The adenine phosphoribosyltransferase-encoding gene of Arabidopsis thaliana. AB - The apt gene, coding for adenine phosphoribosyltransferase (APRT), has been isolated from the plant Arabidopsis thaliana. Data from both Southern analysis and characterization of apt clones isolated from a genomic library is consistent with the occurrence of one apt within the A. thaliana genome. Comparison of the nucleotide sequence of the apt gene with its corresponding cDNA indicates that the gene contains five introns, whereas all other apt isolated to date have fewer introns (four in mammals, two in Drosophila). The locations of the introns within the plant apt coding region are not consistent with the placement of introns in the previously isolated apt of murines, human and Drosophila species. In agreement with its expression pattern in vivo, the upstream region of this plant apt is able to express the beta-glucuronidase-encoding gene (gus) in an apparently constitutive manner in transgenic A. thaliana plants. The apt promoter region is notable for its lack of conventional promoter elements such as TATA, CCAAT or G+C-rich sequence elements. PMID- 8206376 TI - Sequences of the ribonucleotide reductase-encoding genes of equine herpesvirus 4. AB - The equine herpesvirus 4 (EHV-4) genes encoding the two subunits of the enzyme ribonucleotide reductase (RR) were cloned and their nucleotide (nt) sequences determined. The large subunit (RR1) is predicted to comprise 789 amino acids (aa), which compares with lengths of 790, 775 and 1137 aa for the RR1 proteins encoded by equine herpesvirus 1 (EHV-1) gene 21, varicella zoster virus (VZV) gene 19 and herpes simplex virus type 1 (HSV-1) UL39, respectively. In common with VZV RR1, the EHV-4 RR1 protein lacks the N-terminal domain of HSV-1 RR1 which possesses protein kinase activity. EHV-4 RR1 demonstrates identities of 88, 52 and 29% with the RR1 proteins of EHV-1, VZV and HSV-1, respectively. The small subunit (RR2) is predicted to be 320 aa in length, which compares with lengths of 321, 306 and 340 aa for the RR2 proteins encoded by EHV-1 gene 20, VZV gene 18 and HSV-1 UL40, respectively. The EHV-4 RR2 protein exhibits identities of 90, 60 and 55% with the RR2 proteins of EHV-1, VZV and HSV-1, respectively. PMID- 8206377 TI - A manganese superoxide dismutase-encoding cDNA from Drosophila melanogaster. AB - A cDNA encoding manganese superoxide dismutase (MnSOD) has been cloned and sequenced from Drosophila melanogaster. This 805-bp complete cDNA carries a single open reading frame which specifies a deduced 217-amino-acid (aa) protein with an average identity of 60.8% with deduced MnSOD aa sequences from Caenorabditis elegans and humans. PMID- 8206378 TI - The primary structure of mantid opsin. AB - The sequence encoding opsin from the mantid Sphodromantis sp. has been determined by dideoxynucleotide sequencing of PCR products from a cDNA derived from eye cup tissue. The 376-amino-acid (aa) residues show approx. 56% identity and 85% similarity to known insect opsins (Drosophila melanogaster and Calliphora erythrocephala). The predicted protein structure, based on the hydropathy profile and placement of key aa residues, reveals a seven-transmembrane structure typical of a rhodopsin. Unlike the previously characterised insect visual pigments which have 3-hydroxy retinal in their binding sites, mantid rhodopsin contains 11-cis retinal. Comparison of transmembrane sequences from the opsin family was performed in order to identify any specific aa substitutions which are able to account for the selection of retinal or its 3-hydroxy derivative by insect opsins. PMID- 8206379 TI - Xenopus laevis B4, an intron-containing oocyte-specific linker histone-encoding gene. AB - We have isolated genomic clones of the Xenopus laevis B4 gene, which encodes a linker histone, and characterized the B4 promoter. B4 mRNA is synthesized in X. laevis oocytes and disappears from the embryo by gastrulation. We find that B4 is present in only one or two copies per haploid genome and that it contains introns. Tissue-specific expression, a low copy number and presence of introns are all unusual features for vertebrate genes encoding linker histones. PMID- 8206380 TI - Secretory production of chicken ovomucoid domain 3 by Escherichia coli and alteration of inhibitory specificity toward proteases by substitution of the P1 site residue. AB - Ovomucoids are commonly present in bird egg white and exhibit inhibitory activity toward various serine proteases. To investigate the structure-function relationship of ovomucoid domain 3, we established a secretory expression system for the chicken ovomucoid domain 3 (OMCHI3)-encoding gene in Escherichia coli by ligating it downstream from the tac promoter and signal peptide of E. coli alkaline phosphatase. E. coli JM105 was transformed with the resulting plasmid and induced with 1 mM isopropyl-beta-D-thiogalactopyranoside (IPTG). The mature OMCHI3 was detected in the culture supernatant, and was purified to homogeneity by three-step chromatography. Amino-acid sequence analysis showed that processing by the signal peptidase was carried out exactly at the expected site. Measurements of circular dichroism spectra and inhibitory activity indicated that OMCHI3 was produced in the properly folded form. Furthermore, site-specific replacement of the Ala residue at the P1 site with Met or Lys resulted in acquisition of inhibitory activity toward chymotrypsin or trypsin, respectively, indicating that the P1 site is the predominant determinant for inhibitory specificity. PMID- 8206381 TI - Self-amplifying expression from the T7 promoter in 3T3 mouse fibroblasts. AB - To increase the levels of exogenous or foreign gene expression in mammalian cells, this study sought to develop an 'autogene' that will self-amplify. An autogene plasmid, pT7-G1, containing the T7 phage RNA polymerase-encoding modified gene (G1) under control of its cognate T7 promoter, was only obtained when the plasmid contained the encephalomyocarditis (EMC) untranslated sequence. In vitro transcription and translation studies confirmed that both the T7 promoter and the G1 gene were completely functional in the pT7-G1 plasmid. Expression from pT7-G1 was initiated in vivo either by co-transfection with its in vitro transcript or by transfection into NIH3T3 cell lines that stably expressed T7 RNA polymerase enzyme. Use of the pT7-G1 autogene enabled an approx. 50-fold increase in foreign protein production. Northern analysis suggested that this increased expression resulted from the self-amplification of the autogene. By allowing greater expression in cell lines with low T7 RNA polymerase expression, the pT7-G1 plasmid increases the usefulness of the T7 gene system for expression within mammalian cells. PMID- 8206382 TI - Identification of novel alternatively spliced isoforms of the tropomyosin encoding gene, TMnm, in the rat cochlea. AB - Analysis of a rat cochlear cDNA library for the expression of the non-muscle (nm) tropomyosin (TM)-encoding gene (TMnm), demonstrated that four nm isoforms were present. These four TMnm variants are NM-1, NM-2, NM-3 and NM-4. Nucleotide (nt) sequencing revealed that all these isoforms expressed the nm exon 1b sequence, but varied in their usage of the alternatively spliced exons 6a and b and 9a/b and d, representing skeletal muscle (sk) (exons 6b and 9a/b) and nm (6a and 9d) sequences. A novel exon 9 (designated as exon 9c) was associated with the NM-4 isoform and was also found to be expressed in the cochlea. Comparisons of the nt and amino acid (aa) sequences demonstrated a high homology between rat, mouse and human sequences encoding the 'classical' nm isoform, TM30nm, which is designated herein as NM-1. The rat NM-1 nt homology with mouse and human sequences also included the 3' untranslated region. Homologies were found between aa sequences of the C termini of NM-1 and the TM alpha smooth muscle and TM beta nm isoforms, between the sk sequence of NM-3 and the TM alpha and beta sk isoforms, and between the novel 9c sequence of NM-4 and the TM alpha brain-1 isoform. These data predict that the nm isoforms share biochemical properties described for the other TM isoforms. PMID- 8206383 TI - Protein tyrosine kinases transcribed in a murine thymic medullary epithelial cell line. AB - Medullary epithelial cells of the thymus can be activated by contact with thymocytes. We identified a number of protein tyrosine kinases (PTKs) that could be responsible for the tyrosine phosphorylation observed in a murine thymic medullary epithelial cell line (E-5) following complex formation with thymocytes. Degenerate oligodeoxyribonucleotides (oligos) derived from the amino acid (aa) sequence motifs of PTK catalytic domains were used as oligo primers for PCR amplification to determine the PTK genes which are normally transcribed in the E 5 cell line. Amplicons were cloned, sequenced and the deduced aa sequences were compared to known PTK sequences. Among the 13 distinct PTK catalytic domains identified in E-5 cells, two were novel: they were encoded by eteck, a member of the eph sub-family of PTKs, and thy, a member of the src sub-family of PTKs. PMID- 8206384 TI - Sequence of the 5'-flanking region of the rat c-fos proto-oncogene. AB - The proto-oncogene c-fos is an immediate-early gene that becomes activated by a wide variety of extracellular stimuli. Since many studies regarding regulation of c-fos are conducted in vivo using rats, or with rat cell lines, we have cloned the rat c-fos gene in order to verify that the same regulatory elements that have been characterized in the human and mouse c-fos promoter are also present and functional in the rat. The nucleotide (nt) sequence of the 5'-flanking region of the rat c-fos gene displays remarkable similarity with the mouse and human c-fos genes (93 and 77% identity, respectively). cis-Acting regulatory elements, such as the sis-inducible element (SIE), serum-response element (SRE), AP-1 recognition site, calcium/cAMP-response element (Ca/CRE) and TATA box are present in the rat c-fos 5'-flanking region. A putative glucocorticoid-response element (GRE) is present 13 bp downstream from the AP-1-recognition site. PMID- 8206385 TI - Structure of the bovine lactoferrin-encoding gene and its promoter. AB - Lactoferrin (Lf), a ferric ion (Fe3+)-binding glycoprotein, is found most notably in milk, probably to mediate protection against microbial infection of the mammary gland. Based on an initial isolation and sequencing of a complete cDNA of the bovine Lf gene (bLf), the complete gene was obtained from genomic libraries on five overlapping phage lambda EMBL3 clones. A detailed restriction map and the complete exon/intron structure of the gene are presented, together with 1 kb of sequence data of the promoter upstream from the proximal exon. The coding sequence is dispersed over 17 exons spanning 34.5 kb of genomic DNA. While the exons are of similar size, as in other members of the transferrin gene family (Tf), some of the intron sizes are very different. Evolutionary conservation of both exon sizes and their contribution to the various domains of the protein molecule add to the evidence that Lf originated via an internal sequence duplication. The promoter sequence lacks some of the sequence motifs for transcriptional enhancers found in the promoters of human and mouse Lf, suggesting a potential reason for the relatively weak expression of bLf. PMID- 8206386 TI - Lysozyme-encoding bovine cDNAs from neutrophile granulocytes and mammary gland are derived from a different gene than stomach lysozymes. AB - cDNA copies of a bovine lysozyme (bLys)-encoding gene (Lys) were isolated from libraries specific for granulocytes, as well as the lactating mammary gland. Analysis of each of the longest Lys-specific cDNA inserts revealed nucleotide sequence identity over the entire overlap of 1418 bp. Incomplete at the 5' end, the combined sequence codes for 11 of the 18-amino-acid (aa) Lys leader peptide and 130 aa residues of the mature Lys. Similar to mouse and human Lys from blood cells, the encoded protein contains one aa residue more (Pro103) than any of the bLys derived from stomach. Furthermore, unlike any of the known bLys genes, our sequence reveals the copy of a bovine retroposon element in the 3' untranslated region (UTR) of the mRNA approximately at the same position where an Alu retroposon element resides within the human copy of the gene. As a further distinction from bLys expressed in stomach, we identified a segment within the 3'UTR of the mRNA which is conserved between the bovine and human blood cell variants of the Lys, but does not have significant sequence homology to any of the bovine lysozyme genes known so far. By sequence comparisons, we present evidence that this segment has been deleted during evolutionary divergence of the stomach Lys. Hence, we describe the sequence of a heretofore unknown bLys, being expressed in granulocytes. Bearings of our observations on the understanding of Lys evolution are discussed, as well as the possibility that the product of this gene may be responsible for the functional Lys activity in bovine milk. PMID- 8206387 TI - A dog growth hormone cDNA codes for a mature protein identical to pig growth hormone. AB - Although methods for purification of dog (Canis familiaris) growth hormone (cfGH) were described in the late Sixties, the cloning of its cDNA has not been achieved until now. In order to clone the cfGH cDNA, we capitalized on the high degree of nucleotide sequence conservation among mammalian GH genes to design a pair of consensus oligodeoxyribonucleotide primers. With these, and starting with dog pituitary gland total RNA, we specifically amplified the cfGH cDNA using the reverse transcription-polymerase chain reaction. Its coding sequence (651 bp), as well as its 3' untranslated region (101 bp), resemble those of a typical mammalian GH cDNA. Interestingly, its encoded mature protein is identical to pig growth hormone (pGH). PMID- 8206388 TI - Nucleotide sequence of the canine rod-opsin-encoding gene. AB - The major parts of two canine rod-specific opsin (Ops) transcripts have been cloned by polymerase chain reaction from retinal mRNA. Both transcripts are derived from the same gene. The 5' leader sequence of the transcripts was cloned from canine peripheral blood DNA. The transcripts code for a protein of 348 amino acids (aa), M(r) 38,962 (prior to any protein modification). The aa sequence suggests that in common with other sequenced Ops, canine rod Ops contains seven transmembrane domains, and residues believed essential for retinal pigment binding and for palmitate binding are conserved in the canine protein. Northern blotting using the central part of the ops gene as probe suggested that mature transcripts of three different sizes (about 1900, 2600 and 5500 bases) were found in retina. Of these, the 2600-base transcript was the most abundant. RACE cloning of the 3' end of ops showed that at least two of these size classes originate from differential transcript termination. PMID- 8206389 TI - A HeLa-cell-encoded p21 is homologous to transcription elongation factor SII. AB - A 1.2-kb cDNA clone isolated from a HeLa cell library contains an open reading frame encoding a new protein (p21) of 21 kDa that is approx. 48% similar to members of the eukaryotic transcription elongation factor SII (TFIIS) family. The deduced amino-acid sequence of p21 indicates that it is hydrophilic, basic and contains nuclear localization signals, as well as multiple consensus phosphorylation sites. PMID- 8206390 TI - Interactions of nuclear proteins from uninduced, induced and superinduced HeLa cells with metal regulatory elements MRE3 and 4 of the human metallothionein IIa encoding gene. AB - Transcriptional activation of metallothionein (MT)-encoding genes(MT) is regulated during heavy metal induction by short non-identical repeats, termed 'metal regulatory elements' (MRE), present in multiple imperfect copies in MT promoter regions of eukaryotes. Using mobility shift assays, we have studied the interaction between the human MRE 3 and 4 regions (hMRE3/4) of the MTIIa promoter and nuclear proteins from uninduced and Cd(2+)-induced HeLa cells, and from Cd(2+)-superinduced H454 cells, a HeLa-derived Cd(2+)-resistant cell isolate which overexpresses hMTIIa after exposure to metal. A specific complex with a similar electrophoretic mobility was formed in all three extracts. Dialysis of the extracts using EDTA inhibited the formation of the complexes, which could be reconstituted only after the addition of Zn2+. UV cross-linking analyses of the specific complexes formed by the three nuclear extracts interacting with the hMRE3/4 region revealed that in all of them polypeptides were present having similar electrophoretic mobilities and different molecular masses. Mobility shift assays showed no major differences in the binding of nuclear proteins from induced or uninduced cells. Proposed models of activation of metal-induced MT transcription are discussed. PMID- 8206391 TI - Sequence of the human dopachrome tautomerase-encoding TRP-2 cDNA. AB - We have isolated cDNAs for the human TRP-2 gene which represents a third member of the tyrosinase-related gene family and encodes the dopachrome tautomerase activity that functions in the synthesis of melanin pigment. The human TRP-2 protein has 83% identity/90% similarity to the mouse sequence and has all the structural characteristics of the tyrosinase protein family, including a signal peptide, 15 conserved cysteine residues, two copper-binding domains and a C terminal membrane-spanning region. Northern blot analysis reveals that TRP-2 is expressed at high levels in human melanoma cells. PMID- 8206392 TI - Sequence of a cDNA encoding horse growth hormone. AB - A cDNA encoding horse growth hormone (ecGH) was isolated and sequenced. The coding sequence resembles a typical mammalian GH pre-protein and contains a 3' untranslated region of 101 nucleotides carrying two contiguous polyadenylation signals. PMID- 8206393 TI - Biologically active recombinant human complement factor H: synthesis and secretion by the baculovirus system. AB - A complete cDNA clone (4.3 kb) encoding human complement factor H (hCFH; 155 kDa) has been cloned into the pVL1393 baculovirus expression vector and transfected into Spodoptera frugiperda Sf9 insect cells. A biologically active (92 +/- 15%) 140-kDa protein was secreted into the medium with a yield of more than 5 mg/liter. This is the first report of synthesis of biologically active recombinant hCFH in a heterologous system. PMID- 8206394 TI - Isolation and sequence analysis of the human syntaxin-encoding gene. AB - STX-related genes (encoding syntaxin) have been identified in rat and yeast; however, no human STX gene has been isolated thus far. Here, we describe the nucleotide sequence of the first human STX gene isolated from a placental library. It encodes a 297-amino-acid (aa) protein and is 89% identical to the aa sequence of rat STX 4a. PMID- 8206395 TI - Octreotide in gastrointestinal motility disorders. AB - The effects of octreotide on six normal subjects and five patients with scleroderma were investigated. Changes in intestinal motility and in plasma motilin were examined after a single injection of octreotide. Octreotide stimulated intense intestinal motor activity in normal subjects. Motility patterns in the scleroderma patients were chaotic and non-propagative, but, after octreotide was given, became well coordinated, aborally directed, and nearly as intense as in normal volunteers. Clinical responses and changes in breath hydrogen were also evaluated in the five scleroderma patients who had further treatment with octreotide at a dose of 50 micrograms/day subcutaneously for three weeks. A reduction in symptoms of abdominal pain, nausea, vomiting, and bloating was seen. Additionally, there was an improvement in bacterial overgrowth as objectively measured by breath hydrogen testing. The effects of octreotide (100 micrograms/day subcutaneously) on the perception of rectal distension were investigated in a double blind, placebo controlled study in healthy volunteers. Octreotide was shown to reduce the perception of rectal distension without affecting motor pathways or local rectal reflexes. This enhanced tolerance to volume distension seems to result from inhibition of sensory afferent pathways as shown by electroencephalographic studies showing diminished evoked spinal and cortical potentials after octreotide. In irritable bowel syndrome patients with rectal urgency, octreotide reduces rectal pressures and perception after rectal distension to near normal values. PMID- 8206396 TI - Octreotide in variceal bleeding. AB - Bleeding from oesophageal varices has a high death rate. Injection sclerotherapy is the most appropriate treatment but facilities for this are not always available. Balloon tamponade and vasoactive therapy may be used as stop gap measures. Somatostatin and octreotide are therapeutic candidates for the treatment of variceal bleeding and there are several trials that have compared somatostatin and octreotide with other treatments for this condition. The results of these trials are summarised and discussed. A meta analysis of the group of trials of placebo or H2 antagonists v somatostatin or octreotide showed a significant advantage of somatostatin or octreotide in terms of efficacy, but no difference in mortality. The trials discussed seem to show that somatostatin and octreotide are at least as effective as other treatments, with the benefit of fewer adverse effects, and thus represent the best vasoactive agents. Additionally, they may have a role as adjuvant treatment to emergency sclerotherapy for active bleeders and this must be further investigated. PMID- 8206397 TI - Octreotide in the treatment of refractory diarrhoea and intestinal fistulae. AB - Persistent, refractory diarrhoea continues to be an important clinical problem. The mechanisms involved are associated with reduced intestinal absorption and increased intestinal secretion. Reduced intestinal absorption can result from small intestinal resection or from disorders in which there is damage to the small intestine. Motility disorders may also impair absorptive function. The rationale for using octreotide in refractory diarrhoea, intestinal motility disorders, and fistulae relates to its ability to promote intestinal absorption and inhibit gastric, pancreatic, and intestinal secretion. Several clinical studies in patients with short bowel syndrome have reported a reduction of intestinal output in patients taking octreotide compared with controls. Additionally, a number of studies have shown that octreotide improves secretory diarrhoea resulting from neuroendocrine tumours, intestinal infections in AIDS patients, and intestinal graft v host disease. Octreotide may be of use in patients suffering from intestinal motility disorders such as those associated with systemic sclerosis. Octreotide may also be of value in promoting closure of gastrointestinal and pancreatic fistulae. PMID- 8206398 TI - Resetting the CA-125 range for a complete response to chemotherapy: why? PMID- 8206399 TI - An assessment of the value of serum CA 125 measurements in the management of epithelial ovarian carcinoma. AB - The records of 223 patients with epithelial ovarian carcinoma treated at Westmead Hospital and King George V Hospital between 1985 and 1991 were studied retrospectively to compare CA 125 levels with the clinical course of their disease. CA 125 parameters and established predictors of disease were compared using a Cox multivariate analysis to determine their relative prognostic value. The CA 125 trend was the most significant variable followed by the FIGO stage. The initial CA 125 level and nadir CA 125 level, although significant when considered alone, were not significant independent variables. The threshold for a raised CA 125 level was also considered and we propose that a lower level of 15 u/ml may be more useful as a cutoff when following patients with a known history of ovarian carcinoma. The rationale for this is that patients in our study with a nadir level in the intermediate range (15-35 u/ml) invariably developed recurrent disease. PMID- 8206400 TI - A pilot study of intra-arterial carboplatin in patients with recurrent carcinoma of the cervix, postradiation. AB - Twelve patients with recurrent squamous cell carcinoma of the cervix restricted to the pelvis were treated with intra-arterial infusion of carboplatin. The initial carboplatin dose was 300 mg/m2, every 4 weeks, and the dose was escalated to 450 mg/m2. Myelosuppression was the dose-limiting toxicity at the 450 mg/m2 dose. One patient died of treatment-related febrile neutropenia at that dose level. Two patients having received one cycle at 300 mg/m2 suffered grade 3 peripheral paresthesia. There were no objective responses but five patients had a subjective improvement of pain and performance status. PMID- 8206401 TI - Technically accurate intracavitary insertions improve pelvic control and survival among patients with locally advanced carcinoma of the uterine cervix. AB - The purpose of this study was to document whether the technical qualities of a brachytherapy application impacts on the outcome of patients with locally advanced cervix cancer treated by definitive irradiation. A previous report from the patterns of care study demonstrated the importance of brachytherapy in the treatment of locally advanced cervix cancer. Locally advanced disease was defined as FIGO stages Ib (if tumor diameter was < or = 4 cm), IIb (if disease was bilateral or involved the lateral aspect of either parametrium), and III. Localization films from 128 patients with locally advanced squamous cell carcinoma of the cervix were reviewed by a radiation physicist and a radiation oncologist with expertise in gynecologic radiotherapy. All patients received external beam irradiation followed by one brachytherapy application (median point A dose = 8040 cGy; range, 4083-10,020 cGy). Brachytherapy parameters assessed were (a) the distance between the right colpostat source and the distal tandem source, (b) the distance between the left colpostat source and the distal tandem source, and (c) the symmetry of colpostat placement. Implants were scored as "ideal" (n = 8) when all three parameters were deemed satisfactory, "unacceptable" (n = 17) when none of the parameters was deemed satisfactory, and "adequate" (n = 41) in all other cases. Significantly improved 5-year local control was seen when comparing ideal and adequate placements to unacceptable placements (68% vs 34%, P = 0.02). A strong trend toward improved 5-year survival was also noted among the group with ideal and adequate implants as opposed to unacceptable implants (60% vs 40%). Multivariate analysis showed that the technical adequacy of the brachytherapy implant was the most important prognostic discriminant of local control. In conclusion, these analyses demonstrate the direct influence of competent technical implant performance on tumor control and even survival. While only a small fraction of implants for cervical cancer are performed poorly in the United States, there is a need for continued emphasis of the principles for proper implant technique. PMID- 8206402 TI - p53 expression in epithelial ovarian neoplasms: relationship to clinical and pathological parameters, Ki-67 expression and flow cytometry. AB - Epithelial ovarian tumors of varying malignancy as well as normal ovaries were examined for their expression of p53 with the monoclonal antibody PAb1801. Immunohistochemical detection of p53 protein is possible when the gene has been mutated, but not when the normal gene product alone is present. Our results indicate that this tumor suppressor gene may be involved in tumorigenesis, as its expression was detected in both borderline and malignant tumors while normal ovaries and benign ovarian tumors were unstained with the p53 antibody. The presence of p53 was also related to dissemination of disease, residual tumor bulk, and poor differentiation as well as the presence of the proliferation variable Ki-67, another negative prognostic variable. No significant relation could be detected to S-phase fraction or DNA ploidy. Furthermore, the presence of p53 in malignant epithelial ovarian tumors was related to significantly decreased patient survival, with only 36% alive compared to 70% in the p53-negative group (P = 0.002). In the subgroup of patients with residual tumor burden after surgery, those with p53-positive tumors had a significantly (P = 0.05) decreased survival compared to those with p53-negative neoplasms, which further supports an independent role in ovarian cancer malignancy. PMID- 8206403 TI - Prognostic factors in primary fallopian tube carcinoma. Austrian Cooperative Study Group for Fallopian Tube Carcinoma. AB - A retrospective nationwide evaluation of primary fallopian tube carcinomas for a period of 10 years (1980-1990) was performed to evaluate the prognostic impact of various factors. Sixty-six cases were investigated for the prognostic influence of estrogen (ER) and progesterone (PgR) status, mitotic activity, degree of nuclear anaplasia, and inflammatory reaction. ER and PgR receptors were detected by immunohistochemistry from paraffin sections. Forty-two percent were PgR positive and 26% were ER-positive. However, no correlation of steroid receptors with survival could be found. Ninety-two percent of all tumors showed a moderate and high degree of nuclear anaplasia and only 8% showed a low degree of nuclear anaplasia. Thirty-four (52%) samples from all patients revealed low mitotic activity compared to 32 (48%) with an intermediate and high mitotic rate. Twenty four (37%) tissue samples showed a positive inflammatory reaction which correlated with a significantly better outcome compared with tumors without this feature. This finding was also confirmed in multivariate analysis as an independent prognostic factor. PMID- 8206404 TI - Prognostic factors and relapse patterns in early-stage cervical carcinoma after brachytherapy and radical hysterectomy. AB - Patients with cervical carcinoma FIGO stage IB and IIA (n = 167) treated with brachytherapy, radical hysterectomy, and pelvic lymphadenectomy at the University Hospital of Uppsala were evaluated, and a multivariate analysis was performed to reveal clinical and histopathological variables of predictive value of recurrence. The 5-year survival rate was 90%. Nineteen patients developed recurrent disease (11%), 15 of whom died. Patient age, clinical stage, type, and histologic grade of tumor did not indicate an increased risk of recurrence. However, multiparity (3 children or more; relative risk, RR = 4.6), lymph node metastases (RR = 6.4), tumor size (RR = 5.1), and residual carcinoma in the hysterectomy specimen (RR = 3.4) were important predictive indicators of recurrence. The median interval from initial treatment to the diagnosis of recurrence was 15 months. The majority of recurrences occurred during the first 2 years after treatment (74%) and most of them had symptoms (84%). Only three patients with recurrence were diagnosed within our surveillance program. The data suggest that surveillance for recurrence can be made more cost efficient with a more individualized follow-up during the first 2 years after treatment, concentrating on the patients with high-risk factors such as large tumors, residual carcinoma after irradiation therapy, and/or lymph node metastases. PMID- 8206405 TI - Intraperitoneal therapy administered through a Groshong catheter. AB - This report describes a new device for delivery of intraperitoneal therapy. From October 1989 through March 1991, 27 externally accessed Groshong (Bard Access Systems, UT) catheters were placed transabdominally into 24 patients with presumed epithelial ovarian cancer at the conclusion of primary or second-look laparotomy. Total duration of catheter use was 81 months (range, 1-62 weeks). Fifty-seven cycles of intraperitoneal therapy were administered through 18 catheters (range, 1-11). Nine catheters were removed without being used after patients randomized off intraperitoneal treatment arms or were ineligible for intraperitoneal protocols. There were no complications associated with catheter placement or removal. None of the catheters became obstructed or dislodged while in place. There were no cases of infectious peritonitis, although one patient developed an exit-site skin infection. Surgery is not required to remove the Groshong catheter which fosters empiric placement of the device at the time of laparotomy in all patients potentially eligible for intraperitoneal therapy. The device-related infection rate of 4.2 per 100 patients is similar to that described using other implanted devices. Catheter maintenance is easy and patient acceptance is good. The Groshong catheter is a safe, reliable, and acceptable means of delivering intraperitoneal therapy. PMID- 8206406 TI - Extensive primary cytoreductive surgery for advanced epithelial ovarian cancer. AB - This retrospective descriptive study provides our experience with a subset of 30 patients with Stage III or Stage IV ovarian cancer who presented at initial laparotomy with advanced disease in whom large (greater than 10 cm) confluent nodules, plaques, or nodal metastatic deposits were found intraperitoneally. The nature of the extirpative procedures performed resulted in extensive primary cytoreductive surgery involving multiple organ resection. All the patients had removal of their primary tumor from the pelvis, an omentectomy, and appendectomy. In addition to resection of rectosigmoid colon in 27 patients, 11 had concomitant resection of the small bowel and 13 of the large bowel, 3 of which were hemicolectomy. In the remaining 3 patients who did not have rectosigmoid resection a hemicolectomy was performed, 2 of which also had resection of small bowel. Three patients required a primary colostomy, while 1 had a colostomy as a secondary procedure following the development of a rectovaginal fistula. Eight patients had a splenectomy, 2 had resection of portion of the tail of the pancreas, 10 had a partial urinary bladder cystectomy and 2 had a nephrectomy. The average operating time and blood loss was 5 hr 18 min and 2900 ml, respectively. Two patients died within 48 hr postoperatively, two required a second laparotomy for persistent intraabdominal bleeding, and six developed late thrombotic complications. In total 43% of the patients developed serious postoperative complications. We present our findings and allude to the morbidity and mortality that may ensue when such extensive cytoreductive surgery is undertaken. PMID- 8206407 TI - Experience with positron emission tomography (PET) scans in patients with ovarian cancer. AB - Our first year of experience in the use of PET scanning in the management of nine patients with ovarian cancer leads us to conclude that this promising new technique may be more sensitive than either serum CA-125 determinations or computed tomography for the detection and demonstration of residual or recurrent abdominal and pelvic tumor. Seven of these patients underwent second-look laparotomy which confirmed our impressions from preoperative PET scans in six patients, and the one other scan showed a focus of metabolic uptake coinciding with residual tumor in our retrospective review. The clinical courses of two other patients who did not undergo laparotomy confirmed the impressions gained from PET scans. PMID- 8206408 TI - Human papillomavirus detection in cervical carcinoma tissues and paraaortic lymph nodes by the polymerase chain reaction. AB - Tissues of 45 cervical cancers and paraaortic lymph nodes from the same patients were evaluated by polymerase chain reaction with L1 consensus primers and hybridization with type-specific oligomer probes of HPV-6, -11, -16, -18, -31, 33, -35, and -45 for the detection and classification of subtypes of human papillomavirus (HPV). The clinicohistologic findings of surgical specimens from radical hysterectomy were compared with the results of HPV detection to use as a possible prognostic marker for the early detection of paraaortic nodes involvement. Metastasis to paraaortic nodes in cervical cancer, suggesting extrapelvic involvement of tumor, is clinically important to predict prognosis. The HPV-16 DNA was most prevalent in cervical cancers (76%; 34/45). Five tumors were positive for HPV-18, two tumors each were positive for HPV-31 or -33, one tumor was hybridized to HPV-45, and one woman had an unidentified type of HPV. No HPV was detected in three cases of cervical cancer. The histologic types of the cervical cancers were correlated with the HPV types. Of the 39 tissue specimens of squamous carcinomas analyzed, only 2 (5%) showed HPV-18, in contrast to 30 (77%) of 39 squamous carcinomas having HPV-16. Of the 5 cases of adenocarcinomas, 3 (50%) showed HPV-18, and 3 (50%) showed HPV-16. HPV DNAs were detected in histologically negative paraaortic lymph nodes (31%; 14/45): the HPV-positive PCR products from paraaortic nodes were only hybridized to HPV-16. The nature of the relationship between the presence of HPV DNA and node tumor involvement is still not known. HPV-16 DNA in paraaortic nodes may suggest subclinical early metastasis or tumor cells destroyed by immune cells and may provide important information in decisions regarding postoperative adjuvant treatment. The prognostic significance of HPV DNA in histologically negative paraaortic lymph nodes remains to be established after several years of follow-up. PMID- 8206409 TI - Pretreatment plasma levels of fibrinopeptide-A (FPA), D-dimer (DD), and von Willebrand factor (vWF) in patients with ovarian carcinoma. AB - The preoperative plasma levels of fibrinopeptide-A (FPA), D-dimer (DD), and von Willebrand Factor (vWF) were measured in 125 patients with ovarian masses undergoing laparotomy and in 88 healthy nonpregnant women as controls. FPA, DD, and vWF levels were significantly higher in the 58 patients with ovarian carcinoma than in the 67 patients with benign ovarian disease or controls. FPA and DD values were significantly higher in advanced (FIGO stage III-IV) than in early ovarian carcinoma. Among patients with advanced disease, FPA and DD levels correlated with none of the common clinicopathological prognostic variables; conversely, vWF values were related to FIGO stage (IV versus III, P < 0.02) and size of residual disease after initial surgery (> 2 cm versus < or = 2 cm, P < 0.05). In conclusion, increased fibrin production and degradation occur in patients with ovarian carcinoma. PMID- 8206411 TI - Primary lung choriocarcinoma masquerading as a metastatic gestational neoplasm. AB - Primary lung choriocarcinoma has rarely been reported. In females, previous pregnancies and other sources of trophoblastic tissue such as a nongestational gonadal choriocarcinoma must be excluded before the diagnosis can be made. Here we present a young female patient initially diagnosed as having a metastatic gestational neoplasm who was unresponsive to standard single and multiagent chemotherapy. A total abdominal hysterectomy and bilateral salpingo-oopherectomy failed to reveal the source of production of beta HCG. At the time of her thoracotomy and lobectomy, performed for a lung nodule, she was found to have a primary lung choriocarcinoma. The patient received no further chemotherapy and has remained disease free for more than 3 years. This is the first recorded case of a lung choriocarcinoma that has been successfully treated where the patient has remained free of disease for more than 1 year. PMID- 8206410 TI - Endometrial cancer and abdominal wound recurrence. AB - A 65-year-old woman had a total abdominal hysterectomy and bilateral salpingo oophorectomy through a Pfannenstiel incision for a Stage Ib, Grade 2 endometrial adenocarcinoma with extension to the middle third of the myometrium. No adjuvant treatment was given. She presented 7 years later with a large suprapubic mass and the entire lower central abdominal wall was removed and closed with Marlex mesh. Pathology revealed a moderately well-differentiated adenocarcinoma, very similar to the previous cancer with follow-up at 15 months revealing no evidence of recurrence. This case represents growth of implanted tumor cells in the incision that occurred 7 years previously at the time of an uneventful hysterectomy without tumor transgression. It is felt that there was intraoperative tumor cell extrusion through the cervical os with subsequent growth of viable tumor cells. PMID- 8206412 TI - Basal cell carcinoma of the vulva with groin node metastasis. AB - There have been five previous well-documented cases of metastatic vulvar basal cell cancer in the literature. We now present the sixth case-an 86-year-old patient with vulvar basal cell cancer metastatic to an ipsilateral groin node. She was treated with radical vulvectomy and bilateral inguinofemoral lymphadenectomy and remains free of disease 1 year later. PMID- 8206413 TI - Pregnancy coexisting with serous papillary adenocarcinoma involving both uterus and ovary. AB - Less than 100 cases have been reported involving coexistent pregnancy and endometrial cancer of epithelial ovarian cancer. Only one case, histologically an endometrioid adenocarcinoma, demonstrated simultaneous involvement of endometrium and ovary. We report an additional case involving both uterus and ovary coexisting with pregnancy but of a serous papillary histology. A viable preterm infant was delivered. The mother is currently without evidence of disease on cisplatin-based chemotherapy. PMID- 8206414 TI - Extragenital adenosarcoma arising in the pouch of Douglas. AB - We describe a rare case of extrauterine adenosarcoma, the first arising in the Pouch of Douglas, in a 49-year-old premenopausal woman with an elevated CA 125. The tumor consisted of benign glandular and malignant stromal elements. There was no associated endometriosis. Previously reported cases of extragenital adenosarcomas are reviewed. PMID- 8206415 TI - Successful percutaneous drainage of gluteal pyomyositis occurring after intra arterial chemotherapy and pelvic irradiation. AB - Pyomyositis, an unusual infection of large skeletal muscles, developed in a woman with a history of bulky stage IIIB cervical cancer. Three years prior, the woman had undergone aggressive neoadjuvant intra-arterial chemotherapy followed by pelvic irradiation. The overwhelming majority of pyomyositis cases is caused by Staphylococcus aureus. Group B beta-hemolytic streptococcus, an organism that rarely causes this infection, was isolated in this case. Although surgical drainage is the most common approach, successful percutaneous drainage was accomplished. Pyomyositis has only recently been reported in non-tropical climates. The presentation, diagnosis, risk factors, and management of pyomyositis are discussed. PMID- 8206416 TI - Ovarian carcinoma presenting as intra-abdominal hemorrhage. AB - Ovarian carcinoma commonly has an insidious onset. By the time the diagnosis is made, advanced disease is usually present. Rarely does a patient have acute symptoms which require immediate medical attention and lead to the correct diagnosis. A 40-year-old white female presented with lower abdominal pain, nausea, and light-headedness. Physical examination revealed a markedly tender lower abdomen with the right lower quadrant slightly more tender than the left. Hemoglobin level was noted to have decreased 2.6 g/dl over 16 hr. At exploratory laparotomy, 1500 cc of blood and a ruptured right ovarian mass were found. Pathologic analysis revealed a malignant mixed mesodermal tumor of the right ovary and an endometrioma of the left ovary. In conclusion, ovarian carcinoma may present as an acute abdomen because of intra-abdominal hemorrhage. It should be part of the differential diagnosis in a woman with an acute surgical abdomen and a hemoperitoneum. PMID- 8206417 TI - Annual birth patterns of savanna baboons (Papio cynocephalus anubis) over a ten year period at Gilgil, Kenya. AB - Most cercopithecines reproduce on a seasonal basis, but the proximate mechanisms influencing birth periodicity are often unclear. We analyze 10 years of data from the Gilgil Baboon Project (Kenya) in order to examine the relationship between annual birth patterns and rainfall. Savanna baboons at Gilgil copulated in all months of the year, and births did not occur on a seasonal basis. Annual rainfall patterns showed no association with annual birth patterns, but the chances of conception were significantly greater following the end of the long rainy season than at other times of the year. Nonseasonal reproduction is a general characteristic of savanna baboons (Papio cynocephalus subsp.) throughout Africa. The extreme dietary diversity of baboons enables them to utilize a wide variety of resources and facultatively manipulate the timing of different stages in the reproductive cycle in accordance with resource availability. We predict that nonseasonality of reproduction will be more likely to occur among species with a large dietary diversity than among species with a more restricted diet. PMID- 8206418 TI - Social organization in a wild population of Callithrix jacchus. I. Group composition and dynamics. AB - Data are presented on group dynamics in a wild population of the common marmoset, Callithrix jacchus, in northeastern Brazil. Three marked and habituated groups were observed, and composition noted, for at least 5 days a month over 12-18 consecutive months. Group sizes ranged from 5 to 15 individuals, and changes in group composition were the result of births, immigrations, and disappearances. No immigrations into the main study groups were observed throughout the study period. None of the three known emigrants was known to join an established or incipient group for up to 10 weeks after their departure. One group contained only breeding individuals and their offspring. Observations of recruitment and loss in the other two groups suggest that they, too, were extended family groups. The group dynamics described in studies of other populations of Callithrix suggest that extended family groups, or at least groups consisting of breeding individuals and their close relatives, may be characteristic of those populations. PMID- 8206419 TI - Habitat, density and group size of primates in a Brazilian tropical forest. AB - Habitats, population densities and group sizes of 5 primate species (Callithrix flaviceps, Callicebus personatus personatus, Cebus apella nigritus, Alouatta fusca clamitans, and Brachyteles arachnoides) were estimated, using the method of repeated transect sampling, in an area of montane pluvial forest in eastern Brazil (Atlantic forest). A. fusca and C. apella had the highest densities in terms of groups and individuals per square kilometer, respectively, while B. arachnoides was least abundant. The highest primate densities were observed in areas of secondary vegetation. Both group sizes and population densities for the 5 species were generally lower at the Reserva Biologica Augusto Ruschi than those reported in other areas of Atlantic forest. Hunting pressure and the different carrying capacity of the habitat are suggested as possible causes for the low number of sightings registered for these species. PMID- 8206420 TI - Passages within a discontinuous canopy: bridging in the red howler monkey (Alouatta seniculus). PMID- 8206421 TI - Kinesiological characteristics of vertical climbing in Ateles geoffroyi and Macaca fuscata. PMID- 8206422 TI - Use of stones in a captive group of Guinea baboons (Papio papio). PMID- 8206423 TI - Mirror-image responses in capuchin monkeys (Cebus capucinus): social responses and use of reflected environmental information. PMID- 8206424 TI - Displacement activities as potential covert signals in primates. PMID- 8206425 TI - 3 beta-Chlorosteroids: artefacts and possible contaminants in food and feed- toxicological effects in mice. AB - 3 beta-Chlorosteroids, such as cholesteryl beta-chloride and sitosteryl beta chloride, are formed during the production of protein hydrolysates, which are useful flavour enhancers. These chlorinated steroids may also attract attention as environmental contaminants if they are released from liquid crystal display devices. The effects of orally administered 3 beta-chlorosteroids were tested in female NMRI mice. The animals were fed cholesteryl beta-chloride or sitosteryl beta-chloride at doses of 1 mg and 10 mg/animal/day, that is, 33 mg and 330 mg/body weight/day, over a period of 3 months. Feed intake, body weight and organ weights of the animals, as well as concentration of 3 beta-chlorosteroids in faeces and various organs and tissues showed that cholesteryl beta-chloride and sitosteryl beta-chloride are not acutely toxic compounds. However, chronic toxicity cannot be excluded because small amounts of 3 beta-chlorosteroids, in particular cholesteryl beta-chloride, were absorbed by the intestinal tract and accumulated in adipose tissue. Histopathological examination of sections of organs and tissues showed no indication of irreversible cell damage in the stomach, duodenum, liver, kidneys and spleen caused by the chlorinated steroids. PMID- 8206426 TI - Developmental effects of combined exposure to ethanol and vitamin A. AB - The potential for ethanol (EtOH) to influence the developmental toxicity of vitamin A was investigated. 11 groups of approximately 31 FDA-bred Osborne-Mendel rats received either a control or isocaloric 6.4% EtOH liquid diet (containing 4000 IU vitamin A/litre) ad lib. The vehicle control, EtOH and pair-fed (pair-fed against the EtOH group) groups received corn oil (the vehicle) by gavage. Vitamin A was administered by gavage without EtOH at 40,000, 80,000, 120,000 or 160,000 IU/kg daily. Vitamin A was administered by gavage at 10,000, 20,000, 40,000 or 80,000 IU/kg with EtOH ad lib., daily throughout the study. Combined EtOH and vitamin A resulted in significant reductions in maternal diet consumption and body weight when doses of vitamin A were as low as 10,000 IU/kg. The most severe effects on overall (days 0-20) maternal body weight gain were observed in the groups receiving 120,000 or 160,000 IU vitamin A/kg alone or EtOH in combination with 80,000 IU vitamin A/kg. The overall diet consumption (days 0-20) paralleled the overall weight gain. In general, pups exposed to ethanol and vitamin A had a tendency to weigh less than those exposed to vitamin A alone, but to weigh more than those exposed to EtOH alone. EtOH combined with vitamin A at 80,000 IU/kg resulted in an increased incidence of cleft palate relative to the vehicle control or either treatment alone. The incidence of exencephaly and protruding tongue was significantly greater in the group given vitamin A at 160,000 IU/kg, compared with the vehicle control group. The most consistent statistically significant skeletal finding in the groups receiving combined treatment was a treatment-related increased incidence of supernumerary ribs [14th rib (C7), 14th rib bud (L1) and 15 ribs]. In addition, the incidence of misshapen zygomatic arch was also significantly increased in the group exposed to EtOH and vitamin A at 80,000 IU/kg. The incidence of moderately enlarged renal pelvis and severely enlarged ureter proximal to the kidney was increased in the group exposed to EtOH and vitamin A at 80,000 IU/kg relative to the vehicle control, or either treatment alone. Therefore, for some of the endpoints examined in this investigation, it would appear that ethanol potentiates the developmental effects of vitamin A. PMID- 8206427 TI - Enhanced teratogenic activity of di-n-butyltin diacetate by carbon tetrachloride pretreatment in rats. AB - Di-n-butyltin diacetate (DBTA) has been shown previously to cause malformations such as cleft mandible, ankyloglossia and fused ribs in rat foetuses after oral treatment of dams on day 8 of gestation. In this study, effects of pretreatment with carbon tetrachloride (CCl4) on the teratogenic activity of DBTA were examined in Wistar rats. Pregnant rats were pretreated sc with CCl4 (0.5 ml/kg) on days 6 and 7 of gestation and were treated orally with DBTA on day 8 of gestation at doses of 0, 4.5, 10 or 22 mg/kg. Caesarean sections were performed on day 20 of gestation, and foetuses were examined for external and skeletal anomalies. Pretreatment with CCl4 enhanced the incidence of external and skeletal malformations caused by DBTA. Concentrations of di-n-butyltin in embryos, maternal liver and maternal blood on day 9 of gestation were increased by CCl4 pretreatment, which inhibited the activity of maternal hepatic microsomal drug metabolizing enzymes. These results suggest that there is little probability that metabolites of DBTA make a critical contribution to the teratogenicity of DBTA. PMID- 8206428 TI - Polyclonal autoreactive IgA increase and mesangial deposition during vomitoxin induced IgA nephropathy in the BALB/c mouse. AB - To establish the relationship between autoreactive antibodies and vomitoxin induced immunoglobulin A (IgA) nephropathy, the effects of dietary vomitoxin exposure on the antigen specificity of serum IgA, IgA-producing cells and accumulated mesangial IgA in BALB/c mice were assessed. Exposure to dietary vomitoxin for 8 wk caused a significant increase in total serum IgA. There was a concurrent significant increase in serum IgA specific for trinitrophenol (TNP), phosphorylcholine, cardiolipin and sphingomyelin compared with controls, suggesting an elevation of autoreactive IgA. Casein, a protein found in the AIN 76A diet, could inhibit binding of serum IgA to sphingomyelin and cardiolipin, indicating that these antibodies may be polyspecific. When enzyme-linked immunospot assay was used to monitor autoreactive IgA production, trends were observed towards increased IgA-secreting cells specific for TNP, cardiolipin and sphingomyelin in Peyer's patches from vomitoxin-fed mice compared with control mice. IgA-producing cells reactive with TNP were increased in the spleen of vomitoxin-fed mice whereas effects on IgA-secreting cells for the other antigens were marginal. Marked deposition of mesangial IgA was also observed in vomitoxin fed mice compared with controls. When IgA was eluted from the kidney sections of treated mice and tested by enzyme-linked immunosorbent assay, it exhibited a strong binding to the above antigen panel as well as inulin, DNA and casein. These data suggest that dietary vomitoxin induced the polyclonal activation of IgA-producing cells and that resultant autoreactive IgA was subsequently deposited in the kidney mesangium. PMID- 8206430 TI - Studies on the mechanism of intestinal passage of the food comutagen harman, in the rabbit. AB - The passage of harman (Ha) across rabbit jejunum and its effects on electrical parameters of the intestinal epithelium were studied in vitro using Ussing chambers. A linear relationship between mucosal to serosal flux (Jm-s) and the concentration of Ha (0.25-2 mM) was found. Ha elicited a dose-related decrease in short-circuit current, but did not affect transmural potential difference. At 2 mM, Ha decreased tissue conductance. Despite changes of electrical parameters, Jm s of Ha was not modified by metabolic effectors such as glucose, colchicine, 2,4 dinitrophenol and ouabain, indicating that passage was dependent neither on membrane movements nor on cell energy. The transport of Ha was not dependent on Na+, but Ha inhibited in a dose-related manner the cotransport of Na+ and glucose. Luminal sodium taurocholate or beta-lactoglobulin had no appreciable effect on transport of Ha, but ethanol elicited a 45% increase in Ha permeability. These results indicate (1) that substantial amounts of Ha can cross the intestinal epithelium by the transcellular pathway and (2) that the passage of Ha, which appears to be diffusional, is not affected by luminal solutes such as glucose, sodium taurocholate and beta-lactoglobulin, but is markedly enhanced by ethanol. PMID- 8206429 TI - Polyspecific and autoreactive IgA secreted by hybridomas derived from Peyer's patches of vomitoxin-fed mice: characterization and possible pathogenic role in IgA nephropathy. AB - A total of 122 immunoglobulin (Ig)A-producing hybridoma clones were isolated from the Peyer's patches of vomitoxin-fed BALB/c mice and the resultant antibodies were characterized for their antigenic specificity and pathogenic potential. When reactivity was tested against a panel consisting of DNA, sphingomyelin, thyroglobulin, collagen, casein, cardiolipin and bovine serum albumin conjugates of phosphorylcholine, inulin and trinitrophenol that were representative of self and non-self antigens, approximately 95% of the monoclonal IgAs bound to at least one of the panel antigens and 80% bound to more than one antigen. The polyspecificity of some of the monoclonal IgAs was further suggested by demonstrating the capacity of one antigen to inhibit binding of monoclonal IgA to another antigen. Protein staining and Western blotting of gradient native polyacrylamide gels, indicated that trimeric IgA predominated in the isolated monoclonal IgAs. Repeated injections of mice with representative monoclonal IgAs induced microhaematuria in three of four of the clones tested but not IgA deposition in the kidney glomerulus. In addition, three of the four monoclonal IgAs caused IgG and C3 deposition in the kidney mesangium. These and previous results suggest that dietary vomitoxin promotes the polyclonal activation and expansion of IgA-secreting B cells at the Peyer's patch level and that resultant polyspecific, autoreactive IgA may contribute to kidney pathogenesis. PMID- 8206431 TI - Studies on the acute effects of coumarin and some coumarin derivatives in the rat. AB - The mechanism of acute coumarin-induced hepatotoxicity in the rat has been investigated by comparing the effects of coumarin with those of a number of methyl-substituted coumarin derivatives. Male Sprague-Dawley rats were given single ip doses of corn oil (control), coumarin (0.86 and 1.71 mmol/kg body weight), 3,4-dimethylcoumarin (3,4-DMC, 1.71 and 2.57 mmol/kg), 3-, 4- and 6 methylcoumarins (3-MC, 4-MC and 6-MC, 1.71 mmol/kg) and 3- and 4 methyloctahydrocoumarins (3-MOHC and 4-MOHC, 2.57 mmol/kg) and hepatotoxicity assessed after 24 hr. Coumarin administration produced dose-related hepatic necrosis and a marked elevation of plasma alanine aminotransferase and aspartate aminotransferase activities. In contrast, none of the coumarin derivatives examined produced either hepatic necrosis or elevated plasma transaminase activities. Treatment with coumarin reduced hepatic microsomal ethylmorphine N demethylase and 7-ethoxycoumarin O-deethylase activities, whereas one or both mixed-function oxidases appeared to be induced by treatment with 3,4-DMC, 4-MC, 3 MOHC and 4-MOHC. These results provide further evidence that acute coumarin induced hepatotoxicity in the rat is due to the formation of a coumarin 3,4 epoxide intermediate. That 3- and/or 4-methyl substitution (i.e. 3-MC, 4-MC and 3,4-DMC) leads to a reduction in coumarin-induced hepatotoxicity, due to diminished formation of 3,4-epoxide intermediates, was confirmed by the results of molecular orbital calculations. PMID- 8206432 TI - Mechanism of trimethylamine-induced inhibition of macromolecular synthesis by mouse embryos in culture. AB - The effects of trimethylamine (TMA) on uptake mechanisms and lysosomal function were studied in mouse embryos, isolated yolk sacs and limb buds. TMA at 0.75 mM did not inhibit uptake of [14C]sucrose by yolk sacs of day 9 embryos or by day 15 isolated yolk sacs but did inhibit uptake of 125I-labelled bovine serum albumin ([125I]BSA) by day 15 isolated yolk sacs. Concentrations of TMA up to 2.5 mM did not inhibit lysosomal degradation of [125I]BSA by isolated yolk sacs, as judged by the release of trichloroacetic acid (TCA)-soluble radioactivity into the culture media. The inhibition of [125I]BSA uptake induced by TMA was reversible on removal of TMA. When day 8 embryos were cultured in serum containing [3H]leucine-labelled proteins, uptake and incorporation of radioactivity in 0.75 mM TMA-treated embryos was 47 and 44%, respectively, of that in untreated controls. TMA at 0.75 mM did not inhibit the uptake and incorporation of free [3H]leucine into embryonic protein nor the amount of free [3H]leucine taken up or incorporated into protein by day 12 isolated limb buds. It is concluded that the reduced macromolecular synthesis in embryos exposed to TMA is due to an inhibition of receptor-mediated uptake of nutrients by the yolk sac. PMID- 8206433 TI - Modulatory effect of piperine on benzo[a]pyrene cytotoxicity and DNA adduct formation in V-79 lung fibroblast cells. AB - Piperine, a major component of black pepper and long peppers, has been reported previously to have an effect on the activation and deactivation of some exogenous substances. In the present study, piperine was found to promote DNA damage and cytotoxicity induced by benzo[a]pyrene (B[a]P) in cultured V-79 lung fibroblast cells. The V-79 cells were treated with a non-toxic dose of piperine (1-20 microM) plus 10 microM B[a]P, or pretreated with piperine for 30 min or 2 hr prior to the administration of 10 microM B[a]P. B[a]P cytotoxicity was potentiated significantly by piperine under each experimental condition. The relative plating efficiency (RPE) was 71% when V-79 cells were exposed to 10 microM B[a]P alone. When the culture was exposed to B[a]P plus piperine or pretreated with piperine for 30 min prior to the administration of B[a]P, the RPE values were 63 and 44% (P < 0.001), respectively. Pretreatment with piperine for 2 hr had no significant effect (P > 0.05). Furthermore, the lowest activities (P < 0.05) of glutathione S-transferase (GST) and uridine diphosphate glucuronyl transferase (UDP-GTase) of piperine-treated V-79 cells occurred 30 min to 1 hr after the piperine pretreatment. Pretreatment of V-79 cells with piperine also caused an increase in the covalent binding of B[a]P-diol-epoxide to DNA, 2.3 times greater than that of the V-79 cells without piperine treatment. These results suggest that the promotion by piperine of B[a]P-induced cytotoxicity in V 79 lung fibroblast cells is due to mechanisms that decrease the activities of GST and UDP-GTase and increase the formation of a B[a]P-DNA adduct. PMID- 8206434 TI - Effect of ethanol on paraquat toxicity in F344 rats. AB - The potential modifying effects of ethanol and paraquat on lesion development in livers and lungs of male F344 rats were studied. Animals were divided into diethylnitrosamine (DEN)-initiated and non-initiated groups, subgroups of each being exposed to 10 ml 20% ethanol/kg body weight, 2.5 or 10 mg paraquat/kg body weight or a combination of 10 ml 20% ethanol/kg body weight and 2.5 or 10 mg paraquat/kg body weight, given by intragastric intubation three times a week. Controls received 10 ml saline/kg body weight. All animals were subjected to two thirds partial hepatectomy at the end of wk 3 and killed at the end of wk 8. All five rats receiving 10 mg paraquat/kg body weight without DEN-pretreatment died before termination of the experiment, but the additional ethanol treatment saved animals: only one of five rats died. Rats administered 2.5 or 10 mg paraquat/kg body weight demonstrated lung toxicity, as evidenced by fibrosis and hyperplasia, but not when simultaneously treated with ethanol in DEN-pretreated groups. In the liver, however, evaluation of glutathione S-transferase placental form (GST-P) positive foci did not reveal any influence of the treatments on lesion development in DEN-initiated animals. It is concluded that ethanol decreases paraquat toxicity, and that neither agent, alone or in combination, exerts any hepatocarcinogenic modification potential. PMID- 8206436 TI - Aluminium in food. PMID- 8206435 TI - Sex and strain differences in mouse hepatic microsomal coumarin 7-hydroxylase activity. AB - Hepatic microsomal coumarin 7-hydroxylase activity has been determined in male and female mice of strains A/J, AKR, BALB/c, CBA/Ca, C3H/He, C57BL/6J, DBA/2 and 129. In males, coumarin 7-hydroxylase activity was highest in liver microsomes from DBA/2 mice and lowest in BALB/c mice. With female mice enzyme activity was highest in DBA/2 and 129 strains, intermediate in the CBA/Ca strain and comparatively low in the other five strains. Marked sex differences were observed in coumarin 7-hydroxylase activity with enzyme activity in female animals from strains DBA/2, 129 and CBA/Ca being 4.8-, 6.2- and 4.8-fold higher, respectively, than in male mice. In contrast, only minor sex and strain differences in levels of total microsomal cytochrome P-450 were observed. These results demonstrate marked sex and strain differences in mouse hepatic microsomal coumarin 7 hydroxylase activity. Such differences may be due to variations in particular cytochrome P-450 isoenzymes such as CYP2A5, not all of which can be explained by the known allelic difference in the Cyp2a-5 locus. PMID- 8206437 TI - Migration from food-contact materials. PMID- 8206438 TI - Carcinogenicity studies of oxolinic acid in rats and mice. AB - A chronic feeding study was conducted to determine the carcinogenic potential of oxolinic acid, an antimicrobial agent, in rats and mice. Oxolinic acid was administered in the diet to Wistar rats (0, 30, 100, 300 or 1000 ppm; 50 rats/dose/sex) for 104 wk and to ICR mice (0, 50, 150 or 500 ppm; 50 mice/dose/sex) for 78 wk. Clinical signs, body weight, food consumption, autopsy findings and histopathological data were noted. Mortality was unaffected by oxolinic acid administration in neither species. In rats, body weight gain was suppressed in both sexes at 1000 ppm. Histopathological examinations conducted after autopsy at 104 wk revealed a slight increase in benign Leydig cell tumours of the testis at 1000 ppm, which did not appear until late in the lifetime of rats. No other treatment-related neoplastic lesions were observed in rats. Non neoplastic lesions in males at 1000 ppm included Leydig cell hyperplasia and tubular atrophy of the testes. In mice, decreased body weight gain was observed in both sexes at 500 ppm, but no non-neoplastic or neoplastic lesions attributable to the treatment with oxolinic acid occurred in either sex. In conclusion, oxolinic acid induced benign Leydig cell tumours of the testis in rats at the highest dose level tested (1000 ppm). The no-effect level for tumour induction was confirmed to be 300 ppm (10.9 mg/kg/day) in rats. None was induced in mice. PMID- 8206439 TI - An immunotoxicity assessment of food flavouring ingredients. AB - A rapid screening protocol incorporating key elements of the US National Toxicology Program's immunotoxicity tier testing strategy was used to evaluate the effects of 35 commonly used food flavouring ingredients on humoral and cell mediated immune responses. The test compounds were administered intragastrically on a daily basis for 5 days at three dose levels to female CD-1 or B6C3F1 mice, 6 8 wk old. A host resistance assay (Listeria monocytogenes bacterial challenge) was conducted to assess cell-mediated immunity. Humoral immunity was measured by the antibody plaque-forming cell (PFC) response to sheep erythrocytes. Body weights, lymphoid organ weights and spleen cellularity were also measured. Cyclophosphamide (80 mg/kg) served as an immunosuppressive positive control agent. The results indicated that the majority of the flavouring ingredients tested did not modulate the cell-mediated or humoral immune response. However, at very high dose levels, two of the materials tested, peppermint oil and citral dimethyl acetal, did increase mortality rate and reduce survival time in the host resistance assay. Neither of these materials significantly altered the PFC response. This rapid, economical screening battery for potential immunotoxicants proved to be a useful means of evaluating a large number of structurally diverse compounds and mixtures to prioritize them for more definitive testing. PMID- 8206440 TI - Mean daily intake of N-nitrosodimethylamine from foods and beverages in France in 1987-1992. AB - N-nitrosodimethylamine (NDMA) contamination was determined in 556 food samples and 75 beverages purchased in eastern France in 1987-1992. NDMA was found in 427 samples (68%). Data amassed enabled the first estimation to be made in France of the mean daily intake of NDMA from French foods and beverages in 1987-1992 (0.19 microgram/day). One-third of this daily exposure resulted from the consumption of alcoholic beverages. PMID- 8206441 TI - Genotoxicity testing of different types of beverages in the Drosophila wing Somatic Mutation And Recombination Test. AB - Five wines and one brandy of Spanish origin as well as three herbal teas and ordinary black tea were tested for genotoxicity in the wing Somatic Mutation And Recombination Test (SMART) which makes use of the two recessive wing cell markers multiple wing hairs (mwh) and flare (flr3) on the left arm of chromosome 3 of Drosophila melanogaster. 3-day-old larvae trans-heterozygous for these two markers were fed the beverages at different concentrations and for different feeding periods using Drosophila instant medium. Somatic mutations or mitotic recombinations induced in the cells of the wing imaginal discs give rise to mutant single or twin spots on the wing blade of the emerging adult flies showing either the mwh phenotype or/and the flr phenotype. One of the red wines showed a clear genotoxic activity that was not due to its ethanol content. Two herbal teas (Urtica dioica, Achillea millefolium) and black tea (Camellia sinensis) proved to be weakly genotoxic as well. Furthermore, it was shown that quercetin and rutin, two flavonols present in beverages of plant origin, also exhibited weak genotoxic activity in the somatic cells of Drosophila. These results demonstrate that Drosophila in vivo somatic assays can detect the genotoxicity of complex mixtures such as beverages. In particular, it is possible to administer these test materials in the same form as that in which they are normally consumed. PMID- 8206442 TI - Three-month oral repeated administration toxicity study of seed saponins of Thea sinensis L. (Ryokucha saponin) in rats. AB - Ryokucha saponin (RSP), which is one of the ingredients of green tea, was administered orally to rats for 3 months at dose levels of 50, 150 and 500 mg/kg/day to assess any toxic effects. As positive control, 1200 mg/kg/day of quillaia saponin (QSP), which contains saponins equivalent in amount to those in 500 mg RSP/kg/day, was administered. The no-effect level of RSP was 50 mg/kg/day and the lowest-observed-effect level of RSP was 150 mg/kg/day for both sexes, so that the true no-effect level of RSP was estimated to be between these dose levels. In addition, it was confirmed that the toxicity of RSP at 500 mg/kg/day was less than that of QSP at 1200 mg/kg/day and RSP was demonstrated to be safer than QSP, which is a permitted food additive. PMID- 8206443 TI - In vitro effect of vegetable and fruit juices on the mutagenicity of 2-amino-3 methylimidazo[4,5-f]quinoline, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline and 2 amino-3,8-dimethylimidazo[4,5-f]quinoxaline. AB - The antimutagenic potencies of the juices of 28 fruits and 34 vegetables commonly consumed in Germany were investigated with respect to the mutagenic activities induced by 2-amino-3-methyl[4,5-f]-quinoline (IQ), and in part by 2-amino-3,4 dimethylimidazo[4,5-f]quinoline (MeIQ) or 2-amino-3,8-dimethylimidazo[4,5 f]quinoxaline (MeIQx) in Salmonella typhimurium TA98 and TA100. With IQ, weak to strong antimutagenic activities were found in 68% of the fruits and 73% of the vegetables that were tested. In fruits, strong antimutagenic activities were detected in bananas, blackberries, blueberries, sweet and sour cherries, blackcurrants and redcurrants, pineapple and watermelon. Moderate antimutagenic activities were detected in greengage, kiwi, mangos, honeydew melons and plums. Weak antimutagenic activities were detected in apple, apricot, mirabelle, pears, peaches and strawberries, whereas white and red grapes and raspberries were inactive, and gooseberries and citrus fruits in general possessed marginal or no antimutagenic activities. In vegetables, strong to moderate antimutagenic activities were found for all cruciferous vegetables, except Chinese cabbage, which had only weak antimutagenic activity. Other vegetables with strong antimutagenic activities were beets, chives, horseradish, onions, rhubarb and spinach. Moderate antimutagenic activities were found with green beans and tomatoes, weak activities in eggplant, garden cress, many lettuces, leeks, mangold, cucumber, pumpkin, radish and summer squash. Asparagus, carrots, fennel leaves, parsley, green peppers and radishes were inactive. When fruit and vegetable juices were heated, a considerable reduction of antimutagenic potencies was seen with apple, apricot, kiwi, pineapple, beets, cabbage (Chinese, Savoy, red and white), cauliflower, leafy lettuce, cucumber, onions, radish and rhubarb. Antimutagenic factors in blackberries, blueberries, sweet and sour cherries, honeydew melons, mirabelle, plums, strawberries, Brussels sprouts, chicory greens, eggplant, garden cress, mangold, pumpkin, lamb's lettuce and spinach were, however, remarkably heat stable. Antimutagenic potencies in bananas, blackcurrants and redcurrants, greengages, gooseberries, mangos, watermelon, green beans, kohlrabi, horseradish, tomatoes and chives were partially reduced. Antimutagenic activities in the juices of eight apple cultivars were moderate in two, weak in four, and marginal or absent in two. No major differences, however, were detected in five batches of oranges and three batches each of grapefruits, asparagus, green beans, broccoli, cauliflower, spinach and tomatoes. No (or only minor) differences were seen between IQ, MeIQ and MeIQx and tester strains TA98 and TA100. Pineapple and celeriac juices inhibited the enzymatic system responsible for the activation of IQ, but had no desmutagenic activity. Peroxidase activity found to be present in broccoli, cauliflower, green beans and tomatoes may contribute to antimutagenic activities in these vegetables. PMID- 8206444 TI - Glufosinate ammonium--some aspects of its mode of action in mammals. AB - The broad-spectrum herbicide glufosinate ammonium is a structural analogue of glutamate and acts in plants by inhibition of glutamine synthetase leading to a complete breakdown of ammonia metabolism. Owing to the structural analogy of glufosinate ammonium to glutamate, its effect on various glutamate-utilizing systems needed to be investigated in mammals. Although in laboratory animals glufosinate ammonium causes an inhibition of glutamine synthetase activity in different tissues, this inhibition led to slight increases of glutamate and ammonia levels at high sublethal and lethal doses only. After oral administration for 28 days, glufosinate ammonium had no effect on glutathione and carbohydrate metabolism and no effect on biosynthesis of non-essential amino acids in rats and dogs. Glufosinate ammonium does not interfere with various neurotransmitter receptors in vitro and does not influence the catecholamine neurotransmitter tissue concentrations after iv application. The results of these studies show that--in contrast to the plant metabolism--in mammals the inhibition of glutamine synthetase activity in various tissues does not lead to a breakdown of ammonia metabolism. The mammalian metabolism obviously compensates for this inhibition of glutamine synthetase activity by various other metabolic pathways. It is concluded that under the conditions of recommended use of glufosinate ammonium as an active ingredient in herbicides, a detrimental effect on the health of both users and consumers is extremely unlikely. PMID- 8206445 TI - Effect of retinol on ochratoxin-produced genotoxicity in mice. AB - Ochratoxin (1 microgram/kg body weight/day), when administered orally daily to albino Swiss mice for 14 continuous days, increased the incidence of abnormalities in mitotic and meiotic metaphase chromosomes, and the gross morphology of the sperm head; the sperm count per unit volume of caput epididymal suspension also decreased. These genotoxic effects were substantially reduced by concurrent oral administration of retinol at double the clinically therapeutic dose. It is possible that the electrophilic metabolites of ochratoxin form adducts with DNA or produce replacement-type mutations. Retinol may achieve its antigenotoxic effect by means of blocks and shunts in the ochratoxin metabolic pathway. Vitamin A-mediated cellular repair and scavenging of the mutagenic radicals can also take place. The vitamin itself has some genotoxic potential. PMID- 8206446 TI - Evaluation of potential genotoxicity of stannous chloride: inactivation, filamentation and lysogenic induction of Escherichia coli. AB - Because of the importance of stannous chloride in various fields of human endeavour, the potential genotoxicity of this reducing agent was evaluated by measurement of either the inactivation or the induction of SOS responses in bacteria. Escherichia coli strains used in this work (wild type, uvrA, recA, lexA and uvrA recA) were treated with stannous chloride; the wild type was found to be the most resistant and the double mutant, the most sensitive strain. As these strains present mutations on specific genes for the repair of DNA, stannous chloride would appear to be capable of inducing and/or producing lesions in DNA and, thus, can be considered to be a potential genotoxic agent. This capability was confirmed by the lysogenic induction of E. coli K12 (lambda) (Inductest) and by microscopic observation of E. coli B filamentation. PMID- 8206447 TI - Established cell lines for safety assessment of food contaminants: differing furazolidone toxicity to V 79, HEp-2 and Caco-2 cells. AB - In vitro models, preferentially derived from human tissues, may be valuable tools to study the biotransformation and toxicity of compounds that may be present as residues in food products. Such residues may represent a risk to human health, and therefore call for increased testing. Three established cell lines were used to study the toxic effect of furazolidone (FZ), a widely used veterinary drug: HEp-2 cells, derived from a human larynx carcinoma, previously used in toxicity screening of several compounds; Caco-2 cells, derived from a human colon adenocarcinoma, able to differentiate partially in culture, and V 79, a fibroblast cell line derived from Chinese hamster lung, widely used to assess direct toxicants. Various toxicity parameters were used, primarily dealing with cell death and cell proliferation. In all cell lines FZ at a concentration of 5 micrograms/ml caused a marked decrease in cell viability and especially in cell proliferation. Inhibition of DNA synthesis has also been observed, even if at higher concentrations. However, only in V 79 cells was the decrease in cell number accompanied by a marked increase in lactate dehydrogenase leakage due to membrane damage. Moreover, the surviving V 79 cells, after removal of FZ, fully recovered from the effect of the drug, as shown by their full capacity to attach to dishes and to form colonies. Surviving cells of the other two cell lines showed much poorer colony-forming ability. Exposure of Caco-2 cells and, to a lesser extent, HEp-2 cells, caused a marked increase in oxygen consumption, that possibly was due to redox cycling of the initially formed radical nitro anion. Biotransformation of the drug by all three cell lines was accompanied by the formation of protein-bound metabolites, HEp-2 being the most active cells. The toxic effects recorded show that cell lines provide a sensitive system in toxicity assessment. Moreover, it may be suggested that a battery of cell lines, including some of human origin, as well as a battery of endpoints, may be of help in addressing further specific mechanistic investigations. PMID- 8206448 TI - Biliary excretion of the mycotoxin fumonisin B1 in rats. AB - The biliary excretion of the mycotoxin fumonisin B1 (FB1), produced by the fungus Fusarium moniliforme Sheldon, has been measured in male Wistar rats. After ip injection of a solution of FB1 (7.5 mg/kg body weight), 67% of the applied dose was recovered in bile over a 24-hr period, 88% of this recovery being excreted in the first 4 hr after dosing. In contrast to these results, a similar dose of FB1 given by gavage resulted in only 0.2% recovery of the toxin in bile over a 24-hr period. Hence, although these results show that biliary excretion is a major route of elimination of FB1 from the circulation, only small amounts of the toxin appeared to be absorbed from the gut in rats. PMID- 8206449 TI - The use of vitreous humor levels of glucose, lactic acid and blood levels of acetone to establish antemortem hyperglycemia in diabetics. AB - Glucose and lactic acid concentrations were measured in 328 autopsy cases. Glucose and lactic acid in vitreous humor and blood levels of acetone were found to be valuable indicators of antemortem hyperglycemia in diabetics. Resuscitation significantly increased glucose concentrations in vitreous humor whereas blood levels of acetone were not significant (< 1 mg/dl: detection limit). Values encountered in postmortem cases are presented and case results are discussed. PMID- 8206450 TI - Fatal overdose of 2,4-dichlorophenoxyacetic acid (2,4-D). AB - An ingestion of an unknown quantity of U 46 D-Fluid (500 g dichlorophenoxyacetic acid/l) in a suicide is described. Although 2,4-dichlorophenoxyacetic acid (2,4 D) is widely used as a herbicide, intoxications are relatively rare. Quantitation of 2,4-D was performed by diethyl ether extraction from acidified samples (viscera) or by deproteinization (blood, plasma) with methanol before HPLC analysis. Postmortem concentrations of 2,4-D in body fluids and tissues are given. The proposed method resulted in a rapid procedure most useful in cases of deliberate poisoning with phenoxyacetic herbicides. PMID- 8206452 TI - Turpentine poisoning: a case report. AB - The use of turpentine oil for suicidal and homicidal purposes has become quite infrequent with the increased availability of pesticides and toxic substances. Available literature exhibits few case reports of turpentine poisoning. Such a case is reported here which presented as status epilepticus, unresponsive to the usual line of treatment. Detailed clinical examination and inquiry into the case history revealed turpentine poisoning. PMID- 8206451 TI - Hypoxanthine in vitreous humor and cerebrospinal fluid--a marker of postmortem interval and prolonged (vital) hypoxia? Remarks also on hypoxanthine in SIDS. AB - Hypoxanthine (Hx) is a degradation product of adenosine. Increased concentrations were reported in cases of hypoxia as well as with prolonged postmortem interval (PMI). Hx is recommended as an indicator of prolonged (cerebral) hypoxia, for example in vitamins of sudden infant death as well as a new biochemical method for estimation of postmortem time. The correlation of vitreous Hx values with the time since death was reported to be even higher than the vitreous potassium (K+) values. The authors' investigations on 92 bodies with known time since death gave a completely opposite result: a much higher correlation between vitreous K+ and time since death than vitreous Hx. The possible discrepancies between these different results will be discussed (disturbing of intra-ocular fluid dynamics by repeated sample-taking in the study of Rognum et al. The results published so far on vitreous Hx values in sudden infant death syndrome (SIDS) cases as an indicator for a prolonged cerebral hypoxia are also not convincing. When vitreous concentrations of newborn infants or infants of age < 6 months are compared to those of older infants or adults the vitreous diameter must be taken into consideration (diffusion gradient; Fick's law of diffusion). The discrepant results on vitreous Hx as a measure of vital hypoxia and PMI will be discussed. The authors' results on Hx determinations on cerebrospinal fluid in comparison to cerebrospinal spinal (CSF) potassium will also be briefly addressed. PMID- 8206453 TI - Report of the European DNA profiling group (EDNAP)--towards standardisation of short tandem repeat (STR) loci. AB - This paper describes a collaborative exercise intended to demonstrate whether uniformity of DNA profiling results could be achieved between European laboratories using short tandem repeat (STR) loci. Two different STRs were chosen -HUMTH01 and the AT-rich HUMACTBP2 (SE33). The former locus has only five common alleles, whereas the latter is complex and has at least 30 alleles. Laboratories were asked to test seven blood stains and to report the results to the coordinating laboratory. The exercise demonstrated that the simple STR systems such as HUMTH01 are more amenable to adoption as standard loci than complex AT rich systems. PMID- 8206454 TI - An unusual morphine fatality. AB - A case is presented of a 90-year-old white female who apparently died of natural causes in a nursing home. Subsequent investigation indicated that the decedent had been administered an unauthorized bolus of morphine just prior to her death. The embalmed body was exhumed, an autopsy performed, and specimens were collected for toxicologic analysis. The liver contained 1.5 mg/kg of free morphine as measured by radioimmunoassay. The presence of morphine was confirmed by gas chromatography/mass spectrometry. A review of the literature as well as in-house data collected from narcotic deaths clearly suggest that the morphine measured in this case was consistent with a lethal concentration. The manner of death was homicide. PMID- 8206455 TI - Are hip fractures caused by falling and breaking or breaking and falling? Photoelastic stress analysis. AB - The distribution of stress in the heads of femurs has been assessed using an engineering technique known as photoelastic stress analysis. The aim of the investigation was to locate and evaluate the probable sites of structure failure in femurs with various axes of loading. The analysis shows that the maximum stress in the upper femur occurs in the cervical region during vertical loading. Lateral loading does not produce significant stress patterns at the sites of extracapsular hip fracture. It is concluded that cervical hip fractures in individuals suffering from osteoporosis result from a combination of fatigue damage and axial muscular compression, rather than forces generated by a fall. This has significance for the medico-legal interpretation of the cause of death following femoral neck fracture. PMID- 8206456 TI - Renal myoglobin in drug addicts: occurrence and significance in a postmortem study. AB - In a 3-year period (1989-1991) a non-selected, consecutive series of 62 deaths in drug addicts was autopsied at the Forensic Institute in Odense. The kidney sections from these addicts were examined for the presence of renal myoglobin using immunohistochemical methods. A reference group consisting of a non selected, non-consecutive series of 58 autopsied non-addicts was likewise investigated for the presence of renal myoglobin. No major differences were demonstrated between the two groups. The presence of renal myoglobin probably indicates a prolonged course of events prior to death (unconsciousness, immobilization, hypovolemia). In sufficient amounts, renal myoglobin may be of importance as a cause of death or a contributing factor to death in both drug addicts and non-addicts. PMID- 8206457 TI - Deaths due to forklift truck accidents. AB - Forklift truck accidents are a common cause of occupational injury and death. The authors review deaths resulting from forklift accidents cases in the years 1984 1992 in Cook County, Illinois (which contains the large city of Chicago). The fatal injuries, the characteristics of the victims, and the circumstances of the deaths are examined. A forklift striking a pedestrian or crushing the operator when tipping over or falling off a dock or truck were the most common causes of death in this study. The authors compare their findings with those found in the literature on the characteristics and prevention of forklift accidents. Also, they comment on the role of the medical examiner's or coroner's office in the investigation of these work-related deaths. PMID- 8206458 TI - Intercostal variation at the sternal end of the rib. AB - The human rib has proven to be an important site for the assessment of age at death in the adult skeleton. The rib phase method, featuring race and sex specific standards developed by two of the authors (Iscan and Loth), is proving successful in paleodemography and forensic anthropology. However, as the authors pointed out in earlier publications, it is not always possible to isolate the fourth rib upon which the standards are based. This can be a factor because although a certain degree of intercostal variation does exist, its extent has not been quantified in a modern forensic population. Therefore the purpose of this paper is to determine if standards from the fourth rib can be used for adjacent ribs 3 and 5. Ribs 3, 4, and 5 were collected at autopsy from recent medical examiner's cases of known age, sex and race. The sample consists of 135 white males and females of age range 3-99 years. Each rib was assigned to an age phase using the established standards. The results of this analysis indicated that > 79% of cases, all three ribs fell into the same phase, and intercostal differences were within one phase for 98% of the sample. It may thus be concluded that age can also be assessed from these adjacent ribs using the present standards. PMID- 8206459 TI - Vitreous alcohol is of limited value in predicting blood alcohol. AB - Vitreous humour alcohol concentration (VHAC) and blood alcohol concentration (BAC) measured by gas chromatography were available from 345 medico-legal autopsies. Simple linear regression with BAC as outcome variable and VHAC as predictor variable (range 1-705 mg%) gave the regression equation BAC = 3.03 + 0.852 VHAC with 95% prediction interval +/- 0.019 square root of [7157272 + (VHAC - 189.7)2] and 99% prediction interval +/- 0.025 square root of [7157272 + (VHAC 189.7)2]. The residual standard deviation of VHAC was 26 mg%, the standard error of the slope 0.0098 and the 95% confidence interval for the slope 0.833-0.871. In practice a BAC of 80 mg% is predicted with 95% certainty by a VHAC of 150 mg% and similarly a BAC of 150 mg% by a VHAC of 232 mg%. The prediction interval is too wide to be of real practical use. Previous authors have provided various formulae, including a simple conversion factor, to predict BAC from VHAC without taking into account the uncertainty of the prediction for an individual subject. A re-analysis of the raw data from previous publications gave in most instances regression equations significantly different from the authors' own. PMID- 8206460 TI - Renal osteodystrophy and dialysis artifacts as indicators of identification. AB - Evidence of rare disease may be useful in the identification of unknown remains. Osteodystrophy is a condition commonly associated with chronic renal failure. The presence of renal osteodystrophy and medical artifacts associated with the treatment of kidney failure in human remains may provide information about the individual's medical history. Currently, there are more than 100,000 patients with end stage renal disease in the United States receiving dialysis treatments to replace kidney function, and hundreds of thousands more who have significant chronic kidney failure and are not yet treated with dialysis. Chronic renal failure frequently leads to disorders in the metabolism of vitamin D, calcium, and parathyroid hormone which are extremely difficult to correct. At least three patterns of skeletal change may result: osteitis fibrosa, characterized by increased bone remodelling, increased osteoclastic activity, peritrabecular fibrosis, and a normal mineralization pattern; osteomalacia, with a markedly increased osteoid surface and volume, and impaired mineralization; and mixed osteodystrophy, with increased bone remodelling and moderately impaired mineralization. While these bone changes may not have any clinical manifestations in most patients, they can been seen radiographically and histologically. This evidence may be useful in identifying remains which have been skeletonized, burned, decomposed, or dismembered. Medical artifacts associated with dialysis treatment, such as catheters, polytetrafluoroethylene grafts, and evidence of surgical procedures, are also useful for identification. PMID- 8206461 TI - An autopsy case of osteogenesis imperfecta initially suspected as child abuse. AB - Osteogenesis imperfecta (OI) is an uncommon congenital disease of collagen synthesis. It has a wide range of phenotypic expressions, but it is classically characterized by varying degrees of bone fragility. Consequently, individuals with OI frequently suffer repeated severe bone injuries from otherwise innocuous traumatic events. In the evaluation of suspected child abuse cases with suspicious fractures, clinicians are taught to rule out the possibility of OI. However, because OI is quite rare, this possible diagnosis may be overlooked in situations where the child seems to have clearly suffered non-accidental trauma. OI may potentially be mistaken for child abuse by an inexperienced examiner. An autopsy case of osteogenesis imperfecta that was initially diagnosed as child abuse is presented. PMID- 8206462 TI - [Gottfried Benn and psychiatry]. AB - As a young physician the poet Gottfried Benn (1886-1956) gave up a promising career in psychiatry after short period in practice. A psychodynamic analysis of this failure stresses the importance of the relationship of father and son in adolescence for the maturing of ego identity and ego ideal. At the beginning of this century psychiatry was a medical field with strong materialistic and biologistic positions. Benn embraced this position and tried to distance himself from his father, who was a charismatic priest with psychotherapeutic ambition. Benn experienced difficulty in competing with his father and this can be attributed to disturbances in his relationship to his mother in early childhood. The consequence was e.g. a narcissistic vulnerability in adulthood. The contrast of the splendid success in brain research with its inapplicability in routine therapy was characteristic of the state of psychiatry at the time of Benn's failure. PMID- 8206463 TI - [Hemodynamics of intracranial arteriovenous angiomas]. AB - Intracranial arteriovenous malformations (AVM) show haemodynamically two characteristics: The shunt flow and the perfusion of brain tissue surrounding AVM's. In principle, only tissue perfusion can be measured with the stable-Xe-CT method. In 1954 Murphy defined the steal phenomenon in connection with AVM's. It could therefore be concluded that the AVM shunt perfusion works at the expense of tissue perfusion. This phenomenon has been shown to be responsible for serious episodes of neurological deficits in patients with AVM's. In the present report the haemodynamic influence of the AVM's on the surrounding tissue perfusion was measured with the stable-Xe-CT method which offered high resolution with a precise anatomical correlation. A total of 58 stable-Xe-CT studies were performed on 28 patients, 16 of them postoperatively. In 14 patients not only cerebral blood flow at rest but also regional cerebrovascular reserve capacity after intravenous administration of 1 g Diamox were evaluated. Of the 28 patients, 7 had small (nidus < 4 cm), 16 medium (nidus 4-6 cm), and 5 large (nidus > 6 cm) AVM's. In small and medium AVM's we could demonstrate that blood flow at rest did not differ between both hemispheres. After AVM resection the haemodynamics on both sides were not changed. The regional cerebrovascular reactivity following Diamox administration was 20 ml/100 g/min on the side of AVM compared with 40 ml/100 g/min on the contralateral side. Although this difference was statistically significant, it was within the 95% confidence interval of the normal Diamox reactivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206464 TI - [Functional significance of calcinosis of the basal ganglia via positron emission tomography]. AB - Four patients with symmetrical basal ganglia calcification of different etiologies detected by cranial computed tomography (CT) were clinically evaluated and underwent positron emission tomography (PET) with (18F)-2-fluoro-2-deoxy-D glucose (FDG). All patients were subjected to extensive laboratory investigation and neuropsychological testing. In two patients we found typical laboratory signs of hypoparathyroidism, the other two patients had no endocrinological alterations. Changes of glucose metabolism were mainly detected only in calcified tissues. Particularly in two patients with test psychologically confirmed psychomotoric retardation we did not find any cortical dysfunction. In conclusion, basal ganglia calcification in contrast to primary degenerative diseases has no influence on metabolic function in tissue that is not calcified. PMID- 8206465 TI - [Carbamazepine in treatment of alcohol withdrawal syndrome--an overview of current research]. AB - Originally only intended as an anti-epileptic carbamazepine has nowadays a multitude of applications in the treatment of neurological and psychiatric diseases. It is also being used for the treatment of alcohol withdrawal symptoms. Its pharmacological properties and side-effects are well known and very effective dosage schedules already exist. The exact physiological action of carbamazepine, however, as well as the pathophysiological basis of withdrawal itself have not been entirely discovered. Evidence exists that "anti-kindling-effects" are of particular importance. A number of controlled clinical studies were able to demonstrate the effectiveness of carbamazepine in the treatment of alcohol withdrawal symptoms and have also compared its properties to other substances such as clomethiazole and benzodiazepine. Due to its effectiveness and the lack of additive potential carbamazepine offers a useful alternative to conventional therapeutic approaches, especially in the treatment of mild and moderately severe alcohol withdrawal symptoms. PMID- 8206466 TI - Factors affecting urine EIA sensitivity in the detection of Chlamydia trachomatis in men. AB - OBJECTIVE: This study examined the effects of four variables on the detection of Chlamydia trachomatis in urine from men by enzyme immunoassay (EIA). These variables were: symptoms and signs of urethritis, urine polymorphonuclear leucocytes (PMN), inclusion counts from urethral chlamydia cell cultures and the time between testing and last voiding. METHODS: Included were patients with and without symptoms and/or signs of urethritis attending the Edmonton Sexually Transmitted Disease Clinic. Men were asked to submit a 20 ml volume urine sample. Urethral swabs were collected for gram stain, chlamydia and gonorrhea culture. RESULTS: A total of 318 men were evaluated of whom 47 had chlamydia. Excluding six men who were coinfected with gonorrhoea, sensitivities and specificities of the Microtrak, Chlamydiazyme and IDEIA systems were 78.1% and 99.6%, 75.6% and 100%, and 80.5% and 97.8% respectively. Last void time did not affect the sensitivity. However, sensitivity was best when applied to men with severe evidence of urethritis. CONCLUSION: There is evidence that urine EIA could be used to detect chlamydia in men with acute urethritis but not in those without signs of urethritis. PMID- 8206467 TI - Self-treatment using 0.25%-0.50% podophyllotoxin-ethanol solutions against penile condylomata acuminata: a placebo-controlled comparative study. AB - OBJECTIVE: To compare the efficacy of 0.50% and 0.25% podophyllotoxin preparations against previously untreated penile warts. DESIGN: The study was performed as a double-blind, placebo-controlled investigation on 57 males randomly allocated to one of three groups of 19 males in each, receiving either the placebo solution (70% ethanolic vehicle) or one of the two podophyllotoxin preparations for 1-2 self-treatment courses b.i.d. for three days, separated by a one-week drug-free interval. SETTING: The STD out-patient clinic of the Department of Dermatovenereology at Southern Hospital of Stockholm, Sweden. RESULT: The placebo solution merely exerted a marginal influence on the warts while a primary cure was documented in 72% (13/18) and 81% (13/16) of altogether 34 evaluable men who treated their warts with 0.25% and 0.50% podophyllotoxin, respectively. Follow-up investigation (range 5-23 weeks) was possible for 24 of 26 podophyllotoxin treated men who were primarily cured. Some degree of relapse occurred in nine of them (38%). Of these relapses, warts occurred on previously untreated sites only in three cases (33%), and in another four (44%) relapse was associated with regrowth on treated sites as well as on new sites. When analysing the debulking potential of podophyllotoxin, it appeared that 0.25% podophyllotoxin eradicated 184 of originally 217 warts (85%); the corresponding figure for 0.50% podophyllotoxin was as high as 130 of 135 lesions (96%). Side effects were generally mild-moderate and well tolerated. CONCLUSION: The results underscore the potential usefulness of low-dose podophyllotoxin preparations as first-line chemotherapy of condylomata acuminata for home-treatment. The efficacy from topical use of 0.25% podophyllotoxin detected in the study is certainly of a magnitude signifying that podophyllotoxin concentrations lower than 0.50% deserve further investigation if the drug may be incorporated into alternative vehicles such as creams or ointments. PMID- 8206468 TI - Contraceptive methods and the transmission of HIV: implications for family planning. AB - Heterosexual transmission is the predominant mode of spread of the Human Immunodeficiency Virus (HIV) in most of the world. Whether the use of hormonal contraceptives, IUDs and spermicides is associated with an increased or decreased risk for HIV acquisition remains controversial. Several mechanisms whereby contraceptive methods may influence the transmission of HIV have been proposed. As contraceptive use increases among women of reproductive age, the group most vulnerable to HIV infection, any associations between contraceptive method and HIV risk become even more important. The available studies of these associations are predominantly cross-sectional and give conflicting results. We review the published evidence for associations between HIV and individual contraceptive methods. At this time no definitive conclusions regarding these associations can be drawn. Further research, especially prospective epidemiological studies and basic biological research on mechanisms of heterosexual transmission and the effect of contraceptives on these mechanisms, is urgently needed. PMID- 8206469 TI - The role of microscopy in the diagnosis of sexually transmitted infections in women. AB - INTRODUCTION: Microscopy of genital secretions is routinely performed in female patients attending genitourinary medicine clinics. It diagnoses only 50-70% of gonorrhoea, 40-80% of trichomoniasis and has no value in the diagnosis of chlamydial infection. This study was therefore conducted to reassess the role of routine microscopy in female patients. SUBJECTS AND METHODS: One thousand consecutive women attending the genitourinary medicine clinic of the General Hospital, Birmingham, were studied prospectively. The first 500 women had routine microscopy performed. The second 500 women had microscopy performed only if they complained of symptoms, were known gonorrhoea contacts, or when an abnormal vaginal discharge was noted by the examining clinician. RESULTS: In the routine microscopy group, 46 (9.2%) women had gonorrhea; 30 of these were diagnosed by microscopy and subsequently confirmed on culture and 16 by culture alone; of these, two (4.3%) defaulted from follow-up and were not treated. In the selective microscopy group 139 women (28%) did not require microscopy. Thirty three women had positive culture for Neisseria gonorrhoeae. Of these, seven were diagnosed by microscopy, the rest by culture alone. All patients were successfully treated. No patients with trichomoniasis in the routine microscopy group and only two (4.3%) in the selective microscopy group were lost to follow-up. CONCLUSION: In this study, the selective policy in the second group led to a significant reduction in microscopy. Such a policy has the benefits of saving time for patients and staff, more efficient utilisation of manpower and resources. It did not lead to any significant delay in the diagnosis and treatment of patients with sexually transmitted infections. PMID- 8206470 TI - Treatment of bacterial vaginosis with a three day course of 2% clindamycin vaginal cream: a pilot study. AB - OBJECTIVE: To evaluate the efficacy and safety of a 3 day course of 2% clindamycin cream in the treatment of bacterial vaginosis. DESIGN: A prospective, randomised, double blind, placebo controlled study. SETTING: Department of Genitourinary Medicine, Royal Liverpool University Hospital. SUBJECTS: 55 female patients aged 18 years and over, and premenopausal, who spontaneously or after questioning complained of symptoms of bacterial vaginosis. RESULTS: 55 patients were enrolled. 44 patients were evaluable at Visit 1 when among the 23 who received clindamycin cream bacterial vaginosis was not present in 22 (95.6%) and only one failed treatment. Of the 21 patients in the placebo group only one (4.8%) patient was cured and 20 (95.2%) were failures. Of the 17 patients evaluable at Visit 2 in the clindamycin group, bacterial vaginosis was not present in 14 (82.4%) and had recurred in three. No serious adverse events were noted in either group. CONCLUSION: This pilot study provides encouraging evidence of the efficacy and safety of a 3 day course of 2% clindamycin cream in bacterial vaginosis. PMID- 8206471 TI - The value of prophylactic (monthly) clotrimazole versus empiric self-treatment in recurrent vaginal candidiasis. AB - OBJECTIVE: To determine the comparative efficacy and cost benefit of prophylactic monthly (perimenstrual) clotrimazole, versus empiric self-treatment with the same agent at the onset of symptoms in recurrent vulvovaginal candidiasis. DESIGN: Prospective, randomised, open cross-over study of women with proven recurrent vulvovaginal candidiasis. Clinical and microbiological assessments were done every two months for 12 months. SETTING: Women's Clinic of a University Teaching Hospital. SUBJECTS: Twenty-three otherwise healthy, non-pregnant women with greater than four proven episodes of candida vaginitis in the last year were enrolled into the study. INTERVENTION: Patients were randomised to receive: (1) a single dose of prophylactic clotrimazole 500 mg ovule just before or on the last day of the menses each month for 6 months; (2) or a single dose of clotrimazole 500 mg ovule empirically at the onset of symptoms for 6 months. After the first 6 months patients were crossed-over to the opposite regimen. MAIN OUTCOME MEASURES: Symptoms of recurrent vulvovaginitis during each period, and number of clotrimazole ovules used for each 6 month period. The personal preference of the patients for the two different regimens were assessed at the end of study. RESULTS: During the prophylactic 6 months period of the study, 23 patients had 50 episodes of symptomatic vaginitis (mean 2.2 episodes per patient), versus 86 episodes (mean 3.7 episodes/patient) during the empiric self-treatment 6 months period (P = 0.05). However, during the prophylactic period a total of 168 clotrimazole ovules were used (mean 7.3 per patient), versus 84 ovules (mean 3.6 per patient) during the empiric self-treatment period, p < 0.001. The personal preference of the patients for the type of regimen employed were 17 (73.9%) in favour of the empirical treatment, versus 4 (17.4%) in favour of the prophylactic treatment and 2 (8.7%) no personal preference, p < 0.01. CONCLUSION: Empiric self treatment is more cost-effective and preferable to patients than cyclical monthly prophylactic use of 500 mg clotrimazole vaginal ovules. PMID- 8206472 TI - Infectious osteitis pubis in an HIV seropositive female. AB - We report a case of infectious osteitis pubis following a first trimester abortion in a female seropositive for the human immunodeficiency virus (HIV). Joint aspiration yielded Pseudomonas aeruginosa and the patient was successfully treated with oral ciprofloxacin. PMID- 8206473 TI - Cutaneous vasculitis as the sole manifestation of disseminated gonococcal infection: case report. AB - One of the possible systemic complications of gonorrhoea is disseminated gonococcal infection (DGI), which is usually characterised by both skin and joint lesions. While joint involvement ranges from tenosynovitis to suppurative arthritis, cutaneous involvement features varied non-specific patterns often clinically and histologically consistent with vasculitis. We report a case of DGI in which an extensive, vesicobullous, haemorrhagic, and necrotic cutaneous vasculitis was the sole manifestation of the disease. PMID- 8206474 TI - Disseminated histoplasmosis in patients with acquired immunodeficiency syndrome. PMID- 8206476 TI - Health of the nation and gonorrhoea. PMID- 8206475 TI - Sexually transmitted diseases in the history of Uganda. AB - First noticed in Uganda in 1863 by a European explorer, sexually transmitted diseases (STDs) were cited as a major cause of morbidity and mortality throughout this century. In 1908 the venereal diseases campaign was launched marking the real introduction of western medicine. By the mid-1920s, the campaign was combined with the medical service but throughout the colonial period (1901-1962) venereal diseases were considered intractable. A 1991 survey revealed alarming incidence rates and in light of the importance of STDs as a co-factor in the transmission of HIV, it is of paramount importance to implement more effective control measures. PMID- 8206477 TI - Severe genital ulceration in two females following self-treatment with podophyllin solutions. PMID- 8206478 TI - Periareolar breast abscess due to Pseudomonas aeruginosa in an HIV antibody positive male. PMID- 8206479 TI - Lactic acidosis, non-Hodgkins lymphoma and the acquired immunodeficiency syndrome. PMID- 8206480 TI - The natural history of HIV infection in women attending a sexually transmitted disease clinic in Dublin. AB - OBJECTIVE: To determine the progression rates to AIDS in women in Dublin. SUBJECTS AND METHODS: 109 HIV-1 seropositive women who presented to the Department of Genitourinary Medicine, St. James's Hospital, Dublin, were included in a retrospective analysis. Of these 101 (93%) were intravenous drug users (IVDUs), 7 were heterosexual partners of IVDUs and one had a hetero-sexual partner of no known risk group. Forty-four women (40%) had had 57 children since the time of their first known HIV seropositive test. Progression rates from CDC Stage 11/111 to AIDS are computed. Progression curves are generated according to the Kaplan-Meier method using the Statistical Analysis Software (SAS). RESULTS: The estimated cumulative progression rate at 5 years was 24% (SE 6.6%). 17 out of 109 (15.6%) developed AIDS. The mean follow up time was 2.8 years (SE 0.2). The prevalence of oesophageal candidiasis taking development of AIDS as the point in time was 9 out of 17 (53%), of Mycobacterium hominis infection (TB) 5 (29%) and of Pneumocystis carcinii pneumonia (PCP) 2 (12%). There was no statistical difference in progression rates to AIDS between those women who had children after becoming infected versus those who had none. CONCLUSIONS: Progression rates to AIDS in Irish women is higher than reported in other studies of homosexual/bisexual men, but is similar to rates estimated for both male and female IVDUs. Oesophageal candidiasis is the commonest presenting AIDS diagnosis followed by TB, while PCP is rare, contrary to the findings of similar studies in the USA. PMID- 8206481 TI - Ceftriaxone in the treatment of chronic donovanosis in central Australia. AB - OBJECTIVES: To determine the effectiveness of intramuscular (IM) ceftriaxone sodium in the treatment of chronic donovanosis, and the acceptability to patients and staff of supervised outpatient treatment in rural clinics. METHODS: We collected demographic and sexual health data from participants using a standard questionnaire, and recorded their donovanosis lesions at baseline using genital diagrams. Treatment consisted of a single daily IM injection of 1 g ceftriaxone diluted in 2 ml of 1% lignocaine. Clinic staff followed patients for between three and 12 months, enabling the detection of late recurrences. SETTING: Rural Aboriginal communities in central Australia. PARTICIPANTS: The study describes eight women and four men with chronic donovanosis in detail, and summarises the outcome in 12 additional cases. All cases presented with advanced lesions which had failed to heal on the standard oral antibiotic regimens used in the region. RESULTS: The mean duration of infection was 3.0 years (SD 1.9 years), and between four and ten courses of antibiotics had been prescribed for six of the 12 patients. Patients received between 7-26g of ceftriaxone sodium. Clinical improvement was dramatic in most lesions, and four patients healed completely without recurrence after a total 7-10g of ceftriaxone. Mild recurrences responded to further ceftriaxone or short courses of oral antibiotics. Treatment was well tolerated, and both patient and staff compliance high. CONCLUSION: Donovanosis is an important cause of chronic genital ulceration in central Australia, and is potentially an important risk factor for HIV transmission in Aboriginal communities. The pharmacokinetics and safety profile of ceftriaxone make it a useful and cost-effective agent in the ambulatory management of donovanosis, especially in remote communities. Supervised multidrug regimens of two or more long-acting agents may provide the best answer in donovanosis, administered through the existing health care infrastructure. PMID- 8206482 TI - High prevalence of Neisseria gonorrhoeae strains with reduced susceptibility to fluoroquinolones in Japan. AB - OBJECTIVE: To study the antibiotic susceptibility of Neisseria gonorrhoeae strains isolated in Japan and, in particular, to examine the possibility of emerging fluoroquinolone resistance. MATERIALS AND METHODS: Sixty-nine strains of Neisseria gonorrhoeae isolated in 1992 were tested for susceptibility to 15 antibiotics including fluoroquinolones and were seroclassified. Twenty-seven strains isolated from 1981 to 1984 were also evaluated as controls. RESULTS: The MIC90 values of norfloxacin, ofloxacin, and ciprofloxacin against the isolates from 1992 were 2.0, 1.0, and 0.5 microgram/ml, respectively. The MIC90 values of norfloxacin, ofloxacin, and ciprofloxacin against the isolates from 1981-84 (controls) were 0.25, 0.125, and 0.063 microgram/ml, respectively. These results indicate that the MIC90 values of norfloxacin, ofloxacin, and ciprofloxacin against the strains from 1992 were 8-fold higher than those against the strains from 1981-84. However, there were no significant differences in susceptibility to beta-lactams, tetracyclines, macrolides, and spectinomycin between the isolates from 1992 and those from 1981-84. The majority of the isolates belonged to the WII/WIII serogroup. There was no relationship between fluoroquinolone resistance and serogroup. CONCLUSIONS: Fluoroquinolones have been used frequently as first line therapy and have provided excellent clinical efficacy for gonococcal infections for the last several years in Japan. However, our data indicate that a rapid decrease in the susceptibility of Neisseria gonorrhoeae to fluoroquinolones is occurring in our country. PMID- 8206483 TI - Sexually transmitted diseases in transient British forces in the tropics. AB - OBJECTIVE: To compare the incidence of sexually transmitted diseases (STD) in British troops in the tropics with that in a standard population. DESIGN: Retrospective analysis of STD clinic records over one calendar year. SETTING: A British Military Hospital in the Tropics serving 1441 resident personnel. SUBJECTS: All patients attending a STD clinic. MAIN FINDINGS: 815 cases of STD were recorded during the study period, giving incidence rate of 56,558 per 100,000 population per year. When compared with a matched population from England and Wales, the age standardised relative risk for STD amongst tropical troops was 25.0 (95% confidence interval 24.9 to 25.1). Thirty nine percent of cases reported prostitute contact as a source of their disease. Of patients questioned about condom usage, 70% reported that they did not normally use a condom. CONCLUSIONS: British troops spending short periods of time in a tropical environment are significantly more likely to acquire a STD than men in the same age groups in England and Wales. The proportions of cases who reported that they did not use condoms and the number who cited prostitute contact as a source of infection indicate that even greater sexual education of troops on deployment overseas may be required. PMID- 8206484 TI - Chlamydia trachomatis in women: the more you look, the more you find. AB - OBJECTIVE: To determine the extent to which testing of multiple sites and samples is required to define whether a woman is Chlamydia trachomatis-positive. DESIGN: One-hundred and fifty women attending the Genitourinary Medicine clinic at St Mary's Hospital were enrolled; they had not received antichlamydial antibiotics in the previous three months, were not in a high-risk group for HIV infection, or pregnant, or using an intrauterine contraceptive device. Thirty-two women were re examined three months after recruitment. METHODS: An urethral specimen was Gram stained (smear) and cultured for gonococci. Another urethral specimen was taken to detect C trachomatis elementary bodies (EBs) by the MicroTrak direct fluorescent antibody (DFA) test (Syva). An endocervical swab specimen was Gram stained (smear) and cultured for gonococci. One of two other endocervical swabs was used for the DFA test and was then placed in medium which was centrifuged in a MicroCentaur at 13,000 rpm for 10 min; the deposit was examined by using the DFA test. The first 15-20 ml of voided urine (first pass urine; FPU) was also centrifuged and the deposit tested similarly. RESULTS: Of 182 cervical smears and/or deposits tested for C trachomatis, 38 were positive; more cervical deposits (37) than smears (26) were positive and, of these, one-fifth of the deposits and one-third of the smears contained fewer than 10 elementary bodies. Of 162 paired urethral smears and FPU deposits available, one or other specimen of 36 pairs was chlamydia-positive, that is 31 smears and 32 deposits; of these, two-fifths of the smears and half of the deposits contained fewer than 10 EBs. Of 150 sets of cervical and urinary tract samples tested, 31 were chlamydia-positive at both sites, six in the cervix alone and four in the urinary tract alone. Of 139 women for whom there were valid first visit sample results, 36 (26%) were chlamydia-positive in the cervix, 34 (25%) in the urinary tract and 41 (29%) had at least one sample from either site positive. Overall, DFA tests of deposits from centrifuged cervical specimens achieved the highest sensitivity (88%) and those of cervical smears the lowest (70%). CONCLUSIONS: Deposits from centrifuged cervical specimens were C trachomatis-positive more often than were cervical smears. Testing deposits from centrifuged urines was as successful as testing urethral smears. One-fifth (cervical deposits) to one-half (urine deposits) of specimens contained fewer than 10 EBs. The urinary tract was chlamydia-positive almost as frequently as the cervix but both sites needed to be tested to define whether a woman was chlamydia-positive. PMID- 8206485 TI - Detection of minimal residual disease in patients with lymphomas using the polymerase chain reaction. PMID- 8206486 TI - Anti-IL-2 receptor monoclonal antibody (anti-Tac) treatment of T-cell lymphoma. AB - The abnormal and activated T cells in certain neoplasms of mononuclear cells, select autoimmune disorders, and organ allograft rejection express the IL-2R alpha subunit identified by the anti-Tac monoclonal antibody. In contrast, normal resting cells do not express this inducible receptor. Patients with ATL were treated with different forms of IL-2R-directed therapy to exploit the difference in IL-2R expression between normal and malignant cells. Using the unmodified anti Tac monoclonal antibody, 7 of 19 patients with ATL treated have undergone a remission (2 cases complete), with no toxicity observed. Unmodified murine monoclonal antibodies are limited by their immunogenicity and poor effector functions. Genetic engineering was used to produce humanized anti-Tac that contains the complementarity-determining regions from the mouse with the remainder of the molecule derived from human IgG1-kappa. This antibody is less immunogenic than the murine version, has improved pharmacokinetics, and, in contrast with the parent antibody, manifests ADCC with human mononuclear cells. To enhance its effector function, anti-Tac was armed with toxins or with alpha- and beta-emitting radionuclides. In a clinical trial with 90Y-anti-Tac at the doses used (5, 10, and 15 microCi), 11 of the 17 patients with ATL underwent a partial or sustained a complete remission. Thus, the clinical application of IL 2R-directed therapy represents a new perspective for the treatment of T-cell lymphomas, including HTLV-I-associated ATL. PMID- 8206487 TI - Monoclonal antibodies to detect breast cancer cells in bone marrow. PMID- 8206488 TI - Ondansetron: a specific serotonin antagonist for the prevention of chemotherapy induced vomiting. PMID- 8206489 TI - Isolated limb perfusion with high-dose tumor necrosis factor for extremity melanoma and sarcoma. PMID- 8206490 TI - The significance of the rising incidence of breast cancer in the United States. PMID- 8206491 TI - Treatment of early stage prostate cancer: radical prostatectomy. PMID- 8206492 TI - Treatment of early stage prostate cancer: conservative management--delayed therapy. PMID- 8206493 TI - Immunotoxins and recombinant toxins for cancer treatment. PMID- 8206494 TI - Apoptosis and cancer. PMID- 8206495 TI - Genes coding for tumor rejection antigens: perspectives for specific immunotherapy. PMID- 8206496 TI - Vitamins and cancer: a practical means of prevention? PMID- 8206497 TI - Paragangliomas--a diagnostic dilemma on fine needle aspirates. AB - Paragangliomas are uncommon tumours arising from the neural crest and are widely distributed throughout the body. Because of the morphologic diversity of these tumours fine needle aspirate (FNA) diagnosis is not very accurate in identifying these neoplasms. Review of FNA from seven paragangliomas (three extra-adrenal, three carotid body and one multicentric in location) was conducted to find any diagnostic criteria. On initial morphologic diagnosis five of the seven paragangliomas were considered malignant (four undifferentiated and one adenocarcinoma). Review of these cases in our series made us wiser. Pleomorphic nuclei, prominent nucleoli, clumped chromatin with finely granular cytoplasm and occasional intranuclear cytoplasmic inclusions were characteristically seen and these were probably the cause for misdiagnosis. This lesion must be entertained in an aspirate from the neck or retroperitoneum which contains cells showing marked nuclear pleomorphism with naked nuclei and have a tendency to spindle or from acini. To confirm these cases argyrophilic granules were demonstrated in two of the four cases studied. However, neuron specific enolase and calcitonin were found to be non-contributory. Ultrastructural examination was helpful and done in one case showed abundant neurosecretory granules. PMID- 8206498 TI - Papillary meningioma--a clinicopathological study of six cases. AB - Papillary meningioma is a rare but a well recognised histological variant of meningioma. Only 52 cases are reported in literature till 1991. This report highlights the clinical and histopathological features of papillary meningioma in six patients. Significance of making an accurate histopathological diagnosis and its relevance in the management of patients with papillary meningioma is emphasised. PMID- 8206499 TI - Myelodysplastic syndrome. A clinical and pathological analysis of 88 patients. AB - Eighty eight patients with myelodysplastic syndromes were studied to determine the clinical and pathological features and the prognosis. All the patients had anemia. Neutropenia was seen in 44% and thrombocytopenia in 78% patients. The subtypes included refractory anemia in six, refractory anemia with ringed sideroblasts in three, refractory anemia with excess blasts in 30, refractory anemia with excess blasts in transformation in 32 and chronic myelomonocytic anemia in 17 patients. Forty four patients who received chemotherapy were evaluable for response. Three of the 15 patients treated with hydroxyurea achieved partial remission. Eighteen patients were treated with low dose cytosine arabinoside and complete remission was achieved in five and partial response in six patients. Aggressive chemotherapy was given to 11 patients at the onset of the illness resulting in complete remission in six and partial response in two patients. Nineteen of the 88 patients transformed to acute myeloid leukemia. The crude survival of all the patients ranged from 15 days to 22.5 months. The mortality was due to hemorrhage in 15% and septicemia in 85%. Our data reveals ineffectiveness of the current therapy and emphasizes on the need to develop newer therapeutic approaches. PMID- 8206500 TI - Carcinoma of buccal mucosa: incidence of regional lymph node involvement. AB - Histopathological findings in 57 surgical specimens of T3 and T4 buccal mucosa cancers are reviewed. The incidence of the well-differentiated tumours (including verrucous carcinoma) was 61%. A moderate degree of lymphocytic infiltration of the tumour was present in 37% of patients. Histologically proven cervical lymph node deposits were present in only 16% of the patients. Amongst the group of patients with clinically enlarged lymph nodes, metastatic disease was histologically demonstrated in 17.5% at level I and 14% at level II of neck nodes. Amongst group of patients with no palpable nodes in the neck, metastatic disease was histologically demonstrated in 11.7% at level I and 9% at level II of neck nodes. These findings contra-indicate an elective neck dissection and indicate the need to confirm histologically the presence of lymph node deposits doing a radical neck dissection in patients with buccal mucosa cancer. This well differentiated tumour has a much lower tendency to metastasize than cancers in other sites of the oral cavity. PMID- 8206501 TI - Sero-prevalence of herpes simplex virus type-2 among cancer cervix patients. AB - Serum samples were collected from 140 cancer cervix patients aged between 25-60 years and also from 20 age matched, married, healthy women to serve as controls. These sera were tested for HSV-2 antibodies by ELISA test and HBsAg by RPHA test. HSV-2 antibodies were detected in 92 (65-71%) and HBsAg in 25 (17.8%) cancer cervix patients. Sera from control group were negative for HSV-2 antibodies and HBsAg. PMID- 8206502 TI - Ectopic hamartomatous thymoma--a case report and review of the literature. PMID- 8206503 TI - Lymphangiovenous malformation--a rare cause of giant retroperitoneal cyst. AB - A giant retroperitoneal cyst manifesting as congenital inguino-scrotal swelling to begin with, is reported. The abdominal swelling became clinically obvious at the age of five years because of rapid enlargement over a period of one month. A multiloculated cyst was revealed on preoperative ultrasonography. Intracystic hemorrhage necessitated emergency surgical exploration and excision. Histology of the cyst revealed lymph-angio-venous malformation. PMID- 8206504 TI - Myxoid lipoma of the tongue: a case report. AB - Myxoid lipoma is a rare variety of lipoma and its occurrence in the oral cavity is a clinically curiosity. One such case is reported. PMID- 8206505 TI - Multicentric gliomas: report of 2 cases. AB - Two cases of multicentric gliomas with long survival are reported. One patient underwent multiple surgical procedures while another had two separate surgical procedures at the same time. Presence of calcification of CT scan in one case raised suspicion for a preoperative diagnosis of oligodendroglioma. Lack of direct continuity or subarachnoid enhancement on CT scan and low histological grade of the tumours suggested their primary multicentric origin. The incidence of multicentric gliomas in our experience is 0.4% amongst 500 glial tumours over a period of eight years. PMID- 8206506 TI - The antigen self-presentation function of the cytotoxic T-cell clone 10BK.1 depends on reciprocal peptide presentation. AB - Cells of the cytotoxic T-cell clone 10BK.1 proliferate in response to ovalbumin (OVA) not only in the presence, but also in the absence, of antigen-presenting cells. This response is the consequence of reciprocal antigen presentation by two 10BK.1 cells. At the single-cell level, we found antigen-induced changes in the cytosolic Ca2+ concentration ([Ca2+]i) only in 10BK.1 cells that had contact with another 10BK.1 cell. This finding suggests that a single cell is unable to present the antigen to itself, and that two 10BK.1 cells are necessary and adequate to present the antigen to each other. Our data indicate that 10BK.1 cells are not capable of processing the OVA molecule. The naturally processed peptide OVA257-264 is a very potent antigen for these cells. A corresponding peptide seems to be present not only in preparations of native OVA, but also in preparations of the commonly used peptide OVA258-276. This 19mer peptide does not bind with high affinity to the relevant Kb class I molecule. PMID- 8206507 TI - Cholera toxin acts as a potent adjuvant for the induction of cytotoxic T lymphocyte responses with non-replicating antigens. AB - Cholera toxin (CT) is a strong systemic and mucosal adjuvant that greatly enhances IgG and IgA immune responses, but its adjuvant effects for cellular immunity, particularly class I-restricted cytotoxic T lymphocyte (CTL) responses, are less well understood. In the present report, CT and the purified non-toxic B component (CTB) were assessed for their ability to facilitate class I-restricted CTL induction to soluble proteins as well as to permit sensitization of target cells for CTL-mediated lysis. Priming for ovalbumin (OVA)-specific CTL occurred following oral exposure to a combination of OVA with CT plus CTB. In addition, CTB mixed with soluble proteins and administered intravenously primed mice for antigen-specific class I-restricted CTL. Target cells could also be sensitized for CTL-mediated killing following their exposure to soluble antigen and CTB in vitro. These results indicate that combinations of CT and CTB not only enhance antibody responses, but also have an immunomodulating effect to allow sensitization and priming for antigen-specific class I-restricted CTL. PMID- 8206508 TI - Interstitial lung macrophages interact with dendritic cells to present antigenic peptides derived from particulate antigens to T cells. AB - When the protective structural and functional barriers of the lung are breached, immune responses must be generated in order to contain invading micro-organisms. This requires the presence of accessory cells capable of phagocytosing and presenting immunogenic peptides to either naive or sensitized T cells. In contrast to dendritic cells (DC) present in the airway epithelium, those within the lung parenchyma do not readily engulf particulates and, therefore, other mechanisms must account for their apparent ability to present immunogenic peptides derived from micro-organisms. The purpose of the present study was to determine the extent to which interstitial macrophages (IM) interact with lung DC to process and present antigenic peptides, derived from particulate, heat-killed Listeria monocytogenes (HKL), to HKL-immune T cells. Results show that highly purified Ia- lung IM avidly phagocytose fluorescent-labelled HKL, but they do not present antigen to primed T cells. Their ability to present antigen is only modestly increased following interferon-gamma (IFN-gamma) stimulation. Conversely, mature DC isolated from the lung interstitium do not phagocytose fluorescent-labelled HKL. In antigen presentation assays, however, addition of 10% (2.5 x 10(3)/ml) Ia- IM to DC and HKL results in a two- to threefold increase in antigen presentation by DC to HKL-immune T cells. Conditioned medium (CM), generated by 2.5 x 10(4)/ml IM induced to phagocytose HKL, when administered to DC and HKL-sensitized T cells without added intact HKL, resulted in brisk mitogenesis, a response that did not occur in T cells sensitized to an irrelevant antigen. Conditioned medium derived from larger numbers of IM was inhibitory. When IM phagocytosed inert polystyrene beads, the resulting CM induced modest T cell mitogenesis, suggesting that small amounts of cytokines were released. The results indicate that in small numbers, IM augment DC function, in part, by the release of antigenic peptides which are then presented by DC to T cells. When present in numbers greater than 50% of DC, however, they inhibit DC function, probably due to the release of soluble inhibitors. PMID- 8206509 TI - Characterization of the immunogenetic basis of ultraviolet-B light effects on contact hypersensitivity induction. AB - Ultraviolet-B (UVB) light has proven to be deleterious to the skin immune system in mice, and one major consequence is impairment of the induction of contact hypersensitivity (CH) to haptens applied to UVB-exposed skin. It has been shown recently that the damaging effects of UVB on CH are mediated primarily by tumour necrosis factor-alpha (TNF-alpha). Moreover, not all strains of mice are equally susceptible to the deleterious effects of UVB. Mice that develop CH when hapten is applied to UVB-exposed skin are termed UVB-resistant (UVB-R), whereas mice that fail to acquire CH under these circumstances are termed UVB-susceptible (UVB S). In the present experiments, we have characterized the UVB-susceptibility of numerous, genetically disparate inbred strains of mice by applying dinitrofluorobenzene (DNFB) epicutaneously to normal and to UVB-exposed body wall skin. The results indicate that the intensities of CH responses of these different strains were distributed in a bimodal fashion, with means at 92% and 28.5% of positive control responses. Among the strains with CH values distributed around the higher mean (i.e. UVB-R mice), the intensity of CH responses after UVB irradiation was uniformly greater than 75% of the intensity found among their positive controls. By contrast, among the strains with CH values distributed around the lower mean (i.e. UVB-S mice), the intensity of CH responses after UVB exposure was uniformly less than 60% of the intensity displayed by their positive controls. The phenotypic traits of UVB-S and UVB-R appear, therefore, to be genetically determined. To that end, we provide in this report additional evidence that UVB-S is a polygenically determined trait that is dictated by polymorphisms at a locus within H-2, and at the Lps locus. Resistance to UVB radiation is a recessive trait, and requires homozygosity of resistance alleles at one or both of the two participating loci, whereas UVB-S acts as a dominant trait. Among H-2 congenic strains of mice that are lipopolysaccharide (LPS) sensitive (Lpsn), UVB radiation impaired the induction of CH to DNFB in all mice except those of the H-2d and H-2a haplotypes. Thus, UVB-susceptibility is dictated by alleles at two, independent genetic loci that can influence transcriptional and translational activity of the Tnf-alpha gene. The potential biological and medical meaning of regulatory polymorphisms governing TNF-alpha production in the skin may be revealed by the recent demonstration that UVB susceptibility and UVB-resistance are phenotypic traits in humans.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8206510 TI - Functional evidence that the HECA-452 antigen is involved in the adhesion of human neutrophils and lymphocytes to tumour necrosis factor-alpha-stimulated endothelial cells. AB - The migration of leucocytes into tissues is a process mediated by leucocyte endothelial interactions, in which adhesion receptors play a crucial role. Recently, it was found that 80-90% of T cells in inflammatory skin diseases were reactive to the monoclonal antibody (mAb) HECA-452+ in contrast to inflamed non cutaneous tissues. It was suggested that the HECA-452 antigen is a homing receptor for lymphocyte migration into skin. This receptor was designated cutaneous lymphocyte-associated antigen or CLA and subsequently identified as a group of related sugar moieties. E-selectin, formerly known as ELAM-1 expressed by the endothelium has been implicated to be a counter-receptor for CLA. In this study, we investigated the adhesion of HECA-452+ leucocytes, i.e. freshly isolated neutrophils and B-cell line BV173 to tumour necrosis factor-alpha (TNF alpha)-stimulated (E-selectin+) endothelial cells. We found that the adhesion of these cells could be inhibited significantly by mAb HECA-452, in a similar fashion to CSLEX1, a mAb specific for E-selectin ligand sialyl Lewisx. This inhibiting effect of both mAb on the adhesion of polymorphonuclear leucocytes (PMN) and BV173 could only be demonstrated when the assay was performed at 4 degrees, but not at 37 degrees. Furthermore, using immunohistochemical analysis we found that the mAb HECA-452-reactive epitope is different from that recognized by CSLEX1. The present results give direct evidence that the antigen recognized by HECA-452 is involved in the adhesion of leucocytes to endothelial cells, although this antigenic epitope is different from that reactive to CSLEX1. PMID- 8206512 TI - Inhibition of interleukin-8 expression by dexamethasone in human cultured airway epithelial cells. AB - Interleukin-8 (IL-8) is a neutrophil chemotactic factor expressed in many cell types, including human airway epithelial cells (HAEC). Inhaled corticosteroids are now used increasingly early in the treatment of airway inflammation such as in asthma, and directly interact with HAEC at relatively high concentrations. We have investigated the effect of dexamethasone on IL-8 expression in primary cultured HAEC obtained from transplantation donors. Northern blot analysis was used to measure IL-8 mRNA levels in HAEC, and radioimmunoassay was used to measure IL-8 protein in culture supernatant fluids. We demonstrated that IL-8 was expressed by primary cultured HAEC and that this was enhanced by IL-1 beta and tumour necrosis factor-alpha stimulation, but not by IL-6 or lipopolysaccharide. Dexamethasone suppressed IL-8 mRNA expression and protein synthesis dose dependently in both resting and stimulated HAEC. The half-life of IL-8 mRNA determined in the presence of actinomycin D was less than 1 hr, and dexamethasone preincubation had no effect on mRNA stability. These results support the view that HAEC may play an important role in the pathogenesis of airway inflammatory diseases, and that glucocorticosteroids may exert their anti-inflammatory effects by blocking IL-8 gene expression and generation in these cells. PMID- 8206511 TI - The acquisition of cytokine responsiveness by murine B cells: a role for antigen and IL-5 in the induction of IL-2 receptors. AB - The mechanism whereby small resting (high buoyant density) murine B cells are induced to express interleukin-2 receptors (IL-2R) and to respond to IL-2 was addressed by staining with anti-IL-2R alpha and -IL-2R beta monoclonal antibodies (mAb), and using receptor-specific cDNA probes. Resting B cells expressed undetectable levels of both IL-2R alpha and beta chains on their surface and did not respond to IL-2, even at supra-physiological concentrations. Sepharose coupled, but not streptavidin-cross-linked, plastic-adsorbed or soluble, anti-mu up-regulated the expression of IL-2R alpha and beta chains and mRNA to levels comparable to those seen in activated T cells. Anti-mu-stimulated B cells responded to IL-2 by incorporation of [3H]thymidine and high rate immunoglobulin (Ig) secretion. Both IL-5 (at optimal concentration) and suboptimal lipopolysaccharide (LPS; 20 ng/ml) induced surface expression of IL-2R alpha. The level of expression induced by IL-5 was equivalent to that on anti-Ig-activated B cells. Neither stimulus induced detectable expression of IL-2R beta, and neither induced B cells to respond to IL-2. IL-2R alpha expression was strongly enhanced, and low levels of IL-2R beta staining and mRNA were induced by the combination of LPS plus IL-5. LPS+IL-5-treated B cells responded to IL-2 by Ig secretion. This indicates that B cells regulate their responsiveness to IL-2 similarly to T cells, via the combined level of expression of IL-2R beta and IL-2R alpha. The synergy between IL-5 and LPS for B-cell responses shows a requirement for complementary stimuli such as would be provided by cytokines, and either cellular interaction or antigen recognition in regulation of B-cell responsiveness to IL 2. PMID- 8206513 TI - Induced hyporesponsiveness in rat Kupffer cells is not specific for lipopolysaccharide. AB - The phenomenon of lipopolysaccharide (LPS)-induced hyporesponsiveness has been reported to occur in macrophage cell lines and primary cells. Hyporesponsiveness was evidenced by a diminution or lack of production of tumour necrosis factor alpha (TNF-alpha) after sequential doses of LPS. In order to characterize the hyporesponsive state in Kupffer cells, the production of TNF-alpha was quantified after varying the concentration of a primary low dose of LPS prior to a challenge with a high, normally stimulatory dose of LPS. The kinetics of establishment of the hyporesponsive state and the effect of varying the bacterial serotype and genus of the challenge dose were determined. The specificity of the hyporesponsive state for LPS was examined. Our results demonstrate that complete hyporesponsiveness with no detectable production of TNF-alpha (< 30 pg/ml) was achieved after a primary dose > or = 10 ng/ml. Establishment of the hyporesponsive state took place within 6 hr. Induction of hyporesponsiveness was not dependent upon the serotype or genus of the challenge dose of LPS and was not specific for LPS. Complete hyporesponsiveness was induced after a primary dose (10 micrograms/ml) of the Gram-positive bacterium Corynebacterium parvum (Cp) and was evident upon challenge with 100 micrograms/ml Cp. The data indicate that the mechanisms by which LPS and Cp induce hyporesponsiveness are not identical in that a primary dose of LPS (10 ng/ml) induced only partial hyporesponsiveness upon challenge with Cp (100 micrograms/ml). These studies improve our understanding of Kupffer cell function. PMID- 8206514 TI - Abnormal TNF-alpha production in diabetes-prone BB rats: enhanced TNF-alpha expression and defective PGE2 feedback inhibition. AB - Upon stimulation with lipopolysaccharide (LPS), peritoneal macrophages from diabetes-prone Bio-Breeding (BB) rats secrete more tumour necrosis factor-alpha (TNF-alpha) than macrophages from diabetes-resistant BB or normal Wistar rats. Enhanced transcription was demonstrated by Northern blot analysis and at the single cell level by mRNA: RNA hybridization. Cytofluorometry analysis showed 2-4 times more plasma membrane and total cell-associated TNF-alpha in macrophages of diabetes-prone BB rats. The analysis of fluorescence intensity showed a single peak, and TNF-alpha mRNA was found in > 90% of macrophages. These findings exclude TNF hypersecretion as being due to an abnormal subfraction of cells. TNF alpha gene hyperexpression in diabetes-prone BB rats was not due to mutations in the regulatory regions of the promoter, which could be shown by cloning and sequencing of the TNF-alpha promoter in the three rat strains. When searching for other regulatory defects we found the production of prostaglandin E2 (PGE2) in response to LPS to be up to 10 times lower in macrophages from diabetes-prone BB rats than from Wistar rats. Furthermore, BB rats macrophages required significantly higher concentrations of PGE2 for suppression of TNF-alpha secretion. We conclude that abnormal TNF-alpha production in macrophages from diabetes-prone BB rats is due to enhanced gene transcription and translation and that this is associated with defective PGE2 feedback inhibition. PMID- 8206515 TI - Cell migration studies in the adoptive transfer of adjuvant arthritis in the Lewis rat. AB - Adjuvant arthritis (AA) can be induced in Lewis rats by a single injection of either heat-killed Mycobacterium tuberculosis or the lipoidal amine CP20961. Concanavalin A (Con A)-stimulated T cells isolated from AA rats are able to adoptively transfer the disease to naive syngeneic recipients. It is unclear, however, whether these transferred cells traffic directly to the joint and initiate arthritis, or whether secondary host cells are responsible for activation of the disease. In the current investigation, T cells labelled with the vital fluorescent dyes Hoechst H33342 and Zynaxis PKH26-G were used to adoptively transfer adjuvant disease to naive recipients. At various stages of disease development sections of ankle joints, together with a range of soft tissues, were examined by fluorescence microscopy to determine the distribution of labelled donor cells in the recipients. Intensely fluorescent lymphocytes were observed in the liver, spleen and lymph nodes within 24 hr of adoptive transfer. Foci of such cells were clearly visible in the primary lymphoid tissues as late as 14 days after transfer. However, close examination of both ankle joint sections and patellar fat pad cells throughout the time-course of the study failed to detect any labelled cells at the lesion site. To develop these observations further, we performed adoptive transfers to nude Lewis rats (rnu/rnu) and found that they were only moderately sensitive and developed, at best, a transient arthritis. This observed difference could not be explained by a generalized lack of an inflammatory response, since we were able to elicit a zymosan peritonitis in the nude rats. However, in nude Lewis rats a striking increase in adoptively transferred AA was obtained after reconstitution with 4 x 10(8) naive syngeneic spleen cells. These combined observations suggest that a host-derived immune cell population is crucial for arthritis induction in the adoptive transfer system. PMID- 8206516 TI - Identification of CD4- CD8- alpha beta T cells in the subarachnoid space of rats with experimental autoimmune encephalomyelitis. A possible route by which effector cells invade the lesions. AB - Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats to elucidate the origin of effector T cells and the route by which they invade lesions. Since mouse studies have suggested that some autoimmune diseases are induced by extrathymic T cells in the liver, we focused our attention on the properties of mononuclear cells (MNC) isolated from the liver and other organs in rats with EAE. A small but significant proportion of LFA-1+ alpha beta T cells was identified in the liver as early as day 7 after immunization with myelin basic protein (MBP). Such LFA-1+ alpha beta T cells were also abundant among MNC attached to the spinal cord (i.e. subarachnoid space), and MNC infiltrated the spinal cord in rats with EAE (day 12). In electron microscopy, MNC attached to the spinal cord were found to be quite unique in terms of their large cell size with well-developed microvilli. More importantly, they were comprised of a considerably large proportion of double-negative CD4- CD8- T cells as well as single-positive CD4+ T cells. However, the cells which infiltrated the spinal cord were mainly CD4+. The present results raise the possibility that the subarachnoid space might be a major site for the expansion of extrathymic T cells in rats with EAE, and that only a limited population of CD4+ T cells invade the spinal cord directly through the outer layer and elicit EAE. PMID- 8206517 TI - Inhibition of Trypanosoma cruzi-specific immune responses by a protein produced by T. cruzi in the course of Chagas' disease. AB - Immunosuppression is readily demonstrable in the acute phase of Trypanosoma cruzi infection but subsides during the chronic phase. In vitro, living T. cruzi induces important alterations in mitogen-activated human T and B lymphocytes and inhibits their capacity to proliferate. These effects are reproduced by a protein spontaneously released by this parasite, termed trypanosomal immunosuppressive factor (TIF). In this study we asked whether TIF would also inhibit a T. cruzi specific immune response and if it is produced in a mammalian host during infection. A significant reduction in the level of [3H]thymidine incorporation by spleen cells from chronically infected mice stimulated with a T. cruzi antigen preparation ensued when TIF was added to the cultures. Production of TIF in T. cruzi-infected individuals was denoted by the ability of serum IgG from either chronically infected patients or mice to abolish, in a concentration-dependent manner, the capacity of TIF to suppress interleukin-2 receptor expression by phytohaemagglutinin-stimulated human lymphocytes. This neutralizing activity was absent in the IgG fractions prepared from sera of healthy volunteers, noninfected mice or mice killed at different times during acute T. cruzi infection. Circulating anti-TIF antibodies represent indirect evidence of TIF production in vivo which, together with TIF-mediated inhibition of T. cruzi-specific lymphoproliferation, raise the possibility that TIF controls anti-parasite immune responses in vivo. The presence of TIF-neutralizing antibodies during chronic but not acute T. cruzi infection may be one of the reasons why immunosuppression is confined to the acute stage. PMID- 8206518 TI - Suppression by Trypanosoma brucei of anaphylaxis-mediated ion transport in the small intestine of rats. AB - The hypothesis that failure of hosts infected with Trypanosoma brucei to express type 1 hypersensitivity is related to this parasite's ability to down-regulate IgE production, and not to an innate lack of allergenicity of T. brucei antigens, was tested by studying anaphylaxis-induced changes in net epithelial ion transport in rats. Transport changes were quantified electrophysiologically in vitro, as a change in transmural short-circuit current when sensitized intestine was challenged with homologous antigen. Rats injected parenterally with trypanosome antigen elicited intestinal anaphylaxis in response to antigenic challenge, whereas the intestine of rats infected with T. brucei failed to respond. Infection with T. brucei also suppressed the anaphylactic response in rats sensitized to and challenged with ovalbumin and T. spiralis-derived antigens. In these cases suppression was related to the ability of T. brucei to block production of IgE, and not to the physiological failure of the epithelial response. However, in rats sensitized by infection with T. spiralis, neither the anaphylactic response nor IgE production were inhibited by T. brucei. Furthermore, intestinal mastocytosis normally associated with trichinosis was unaffected by the trypanosome infection. Results support the conclusion that the failure to express anaphylaxis in T. brucei-infected rats is due to the inhibition of IgE production and not to the lack of allergenicity of trypanosome antigens. PMID- 8206519 TI - Immune responses to Trichinella spiralis and T. pseudospiralis in mice. AB - A comparison was made of the immunological responses of inbred NIH mice to the intestinal stage of infection with two species of the genus Trichinella, T. spiralis and T. pseudospiralis, which are known to have distinct parasitological and pathological relationships with their hosts. The parameters studied, namely antigen-specific IgG1 and IgG2a antibody responses, mucosal mastocytosis, and levels of the cytokines interferon-gamma (IFN-gamma) and interleukin-5 (IL-5) produced by concanavalin A-pulsed mesenteric node lymphocytes in vitro, were chosen to provide information about the relative activities of the Th1 and Th2 T helper (Th) lymphocyte subsets. In this high-responder host the time-course of infections was similar, although initial levels of establishment were considerably higher for T. pseudospiralis. Both species elicited mucosal mastocytosis. Distinct differences were seen in the IgG isotype responses. Trichinella spiralis-infected mice produced a predominantly IgG2a response, whereas T. pseudospiralis elicited an IgG1 response. Cytokine release showed infection dose-related suppression of IFN-gamma and enhancement of IL-5. These effects were most marked in T. pseudospiralis-infected mice, i.e. there was an earlier shut-off of IFN-gamma and an earlier switch to IL-5. These data suggest that the two species of Trichinella show a time-related differential activity of Th subsets during the early stages of infection. The possibility that this may reflect antigenic differences between these closely related species or result from parasite-induced immunological-endocrinological changes is discussed. PMID- 8206520 TI - Goblet cell mucins as the selective barrier for the intestinal helminths: T-cell independent alteration of goblet cell mucins by immunologically 'damaged' Nippostrongylus brasiliensis worms and its significance on the challenge infection with homologous and heterologous parasites. AB - The aim of this study was to examine the role of T cells on the alteration of terminal sugars of goblet cell mucins in the small intestinal mucosa of parasitized rats and to clarify the biological significance of the altered mucins in the mucosal defence against intestinal helminths. For this purpose, Nippostrongylus brasiliensis adult worms obtained from donor rats at 7 ('normal' worms) or 13 days ('damaged' worms) post-infection were implanted intraduodenally into euthymic and hypothymic (rnu/rnu) rats. Expulsion of implanted normal worms and associated goblet cell changes were extremely delayed in hypothymic recipients compared with euthymic recipients. In contrast, intraduodenally implanted damaged worms were expelled by day 5 regardless of the strains. Around the time of expulsion of implanted damaged worms, euthymic recipients showed both goblet cell hyperplasia and alteration of mucins, whereas hypothymic rats showed only the latter. Dexamethasone treatment completely abolished goblet cell changes of both strains of recipients. To clarify the importance of the constitutional changes of goblet cell mucins in mucosal defence, euthymic rats were primed by implantation of damaged worms to induce goblet cell changes, and then 3 or 5 days later they were challenged by implantation with normal worms. The results show that when goblet cell changes were induced by priming with damaged worms, recipient rats could completely prevent the establishment of normal worms. When hypothymic rats were primed and challenged in the same manner, a similar but slightly less preventive effect was observed. Such a protective effect of altered mucins seems to be selective because priming of euthymic rats with damaged N. brasiliensis did not affect the establishment of Strongyloides venezuelensis. These results suggest that: (1) once N. brasiliensis adult worms are 'damaged' by the host's T-cell-dependent immune mechanisms, they can induce alteration of sugar residues of goblet cell mucins via host-mediated, T-cell-independent processes; (2) the expression of such altered mucins is highly effective not only in causing expulsion of established damaged worms but also in preventing establishment of normal worms; and (3) the preventive effect of altered mucins is selective against parasite species. PMID- 8206521 TI - Lymphocyte expression in transgenic trout by mouse immunoglobulin promoter/enhancer. AB - Two groups of transgenic rainbow trout (Oncorhynchus mykiss, Walbaum) have been produced and compared. One group harbored the reporter gene of chloramphenicol acetyltransferase (CAT) associated with mouse immunoglobulin (Ig) promoter/enhancer (pUCL-CAT-E). The other group carried the same reporter gene under the control of the cytomegalovirus promoter/enhancer (pCMV-CAT). Slot blot analysis of DNA from blood cells and other tissues from pUCL-CAT-E fish showed variation of copy number between the major tissues but not between red and white blood cells. Southern blot analysis indicated that multiple copies organized in concatemers were incorporated into the genome. The pCMV-CAT fish had a pronounced expression of CAT in both white and red blood cells. In contrast, activity of CAT was found in the white blood cells of all pUCL-CAT-E fish but not in their red blood cells. Expression in white blood cells was found preferentially in sIg+ cells, indicating that B cells are the major expressors. High expression was also found in spleen and kidney, but the activity found in thymocytes was equal to the background level. Analysis of some major tissues showed high white blood cell expression associated with low tissue expression, except that liver (known to contain lymphoid tissue in fish) was higher. Thus the regulatory elements of the Ig gene from mouse induce a tissue-specific expression in fish. PMID- 8206522 TI - Continued mapping of chromosome 2 genes. AB - This report describes our continued efforts to elucidate the genetic fine structure of the central portion of the mouse chromosome (Chr) 2. Mice from our panel of 28 Chr 2 congenic strains were tested: 1) for the presence of the antigens which stimulate Chr 2-reactive lymphocyte clones in mixed lymphocyte reaction (MLR); 2) for the antigens of histocompatibility (H) genes H-42a and H 45a as determined by allograft rejection; and 3) for their ability to respond to the H-Y antigen in a cell-mediated lysis assay. The results obtained in this study have allowed additional mapping of immunologically involved Chr 2 genes. The gene encoding the antigen which stimulates lymphocyte clone 1C11 can be considered wholly different from other Chr2 H genes on the basis of chromosomal recombination. We have assigned the symbol H-48 to this gene. The following gene order has been established: [H-3, B2m, pa], we, [H-42, H-48,] H-45, IR-H-Y, Hd-1, un, H-13, Aw. The order of the bracketed genes is not known. H-44 maps centromeric to IR-H-Y. The genes encoding the antigens that stimulate lymphocyte clones 2G7, 2C10, 1F6, 1B10, and 1H10 map centromeric to H-45. PMID- 8206523 TI - The extent of the human germline T-cell receptor V beta gene segment repertoire. AB - An assessment of the size of the human TCRBV gene segment repertoire based on the identification of TCRBV gene segments in genomic DNA was undertaken. PCR amplification from cloned and uncloned genomic DNA sources, nucleotide sequencing, Southern blot hybridization, and cosmid cloning were used to identify TCRBV gene segments in multiple unrelated individuals. The key advantages to this approach were: 1) TCRBV gene segments which are expressed only at very low levels in cDNA libraries were still detectable, and 2) it was possible to discriminate between alleles at the same locus vs products of different loci. A total of 63 unique TCRBV gene segments were identified and sequenced. Six of these TCRBV gene segments had not been previously described. Thirty-four cosmid clones containing 51 of the 63 identified TCRBV gene segments were isolated and screened for the presence of additional novel TCRBV subfamily members. These results, obtained by a variety of complementary approaches, indicate that the human TCRBV germline repertoire encodes at least 63 TCRBV gene segments of which 52 are functional. The availability of the majority of these TCRBV gene segments on cosmid clones should facilitate further investigation of germline TCRBV gene segment polymorphism and putative disease associations. PMID- 8206524 TI - A new frequent allele is the missing link in the structural polymorphism of the human mannan-binding protein. AB - Human mannan-binding protein (MBP) is a serum lectin participating in the innate immune defence. Low MBP concentrations are explained by the dominant action of a point mutation at codon 54 of the MBP gene in Eskimos, partially in Caucasians, but not in Africans. A previously described point mutation at codon 57 was very frequent (0.23) in East Africans, low in Caucasians (0.02), and absent in Eskimos. The African population only conformed to Hardy-Weinberg expectation when assuming the existence of an unknown allele, which was subsequently found as a point mutation at codon 52. This allele appeared with a relatively high frequency (0.05) in both Africans and Caucasians, but was absent in Eskimos. Hardy-Weinberg equilibrium is now seen in the investigated ethnic groups. All cases of MBP deficiency may be explained by these three variants. PMID- 8206525 TI - The distribution of Tap2 alleles among laboratory rat RT1 haplotypes. AB - We are reporting the cDNA sequences of Tap2 from two cima and two cimb rat strains. Comparison of the cDNA sequences shows that these alleles fall into two groups, which we refer to as Tap2-A and Tap2-B. We found that alleles from the Tap2-B group are more closely related to the mouse homologue than are Tap2-A alleles, and among the 48 nucleotides which differ between the Tap2-A and Tap2-B cDNAs, three affect restriction sites. We defined pairs of oligonucleotides which allow amplification of the regions bearing these restriction sites from genomic DNA or cDNA, and this technique has been successful for the genotyping of all of the 56 laboratory strains of Rattus norvegicus tested and for five cell lines tested so far. All 14 known RT1 standard haplotypes were tested, and 7 found to belong to the Tap2-B group, and 7 to Tap2-A. We also found that intron sizes among the alleles of the Tap2-B group fall into two subgroups, providing further insight into the phylogeny of these various haplotypes. PMID- 8206527 TI - MHC class I genes are not imprinted in the mouse placenta. PMID- 8206526 TI - Transcriptional suppression of HLA-B expression by c-Myc is mediated through the core promoter elements. AB - In melanoma, HLA class I expression is suppressed by overexpression of the c-myc oncogene. This suppression has severe consequences for the recognition of these tumor cells by the immune system of the organism. We show here that transcription of the HLA-B locus, which is mainly affected by c-Myc, is downmodulated at the level of initiation of transcription. The transcriptional activity of various HLA B reporter constructs was tested in a melanoma cell line with low endogenous c myc expression and in transfectants with high stable and transient c-myc expression. We demonstrated that the responsive region can be mapped to the core promoter region of HLA class I, ruling out any effects of c-myc overexpression on the enhancer A or enhancer B regions. The region subject to downregulation is confined to a 43 base pair fragment encompassing the CCAAT and TATA elements. By coupling this region to a heterologous viral enhancer, we showed that the downmodulation by c-Myc is independent of the presence and nature of an enhancer. These results suggest a mechanism in which c-Myc downregulates the expression of HLA class I genes by interfering with the basal level of transcription. PMID- 8206529 TI - Rearrangements of the human TCRD-deleting elements. PMID- 8206530 TI - Sequences of four new members of the VH7183 gene family in BALB/c mice. PMID- 8206528 TI - Restoration of CTL recognition of a mutant FMP peptide by a compensatory change in HLA-A2. PMID- 8206531 TI - Refined localization of H7 and Ctt1 on distal mouse chromosome 9. PMID- 8206533 TI - Hepatitis E: from hypothesis to reality. PMID- 8206532 TI - The minimal polymorphism of class II E alpha chains is not due to the functional neutrality of mutations. AB - Given the extensive allelic amino acid sequence polymorphism present in the first domain of A alpha, A beta, and E beta chains and its profound effects on class II function, the minimal polymorphism in the mouse E alpha chain (and in its human homologue DR alpha) is paradox. Two possible explanations for the lack of polymorphism in E alpha are: (1) the E alpha chain plays such a uniquely critical structural/functional role in antigen presentation, T-cell activation, repertoire selection, and/or pairing with E beta or other proteins for expression that it cannot vary, and mutations are selected against; (2) the E alpha chain plays a less significant role than the outer domains of other major histocompatibility complex (MHC) proteins in determining the interactions with processed peptides or with T-cell receptor (TCR), so there is no selective pressure to maintain new mutations. To explore this question we compared the ability of transfectants expressing wild type (wt) E alpha E beta d and mutant E alpha wt E beta d proteins to present peptides and bacterial superantigens to T-cell hybridomas. Mutations at the E alpha amino acid positions 31, 52, and 65&66, to residues that represent allelic alternatives in A alpha chains, significantly reduced activation of peptide-specific T hybridomas, and mutations at 71 sometimes enhanced T-cell stimulation. None of the E alpha mutations reduced, and some enhanced, superantigen stimulation of T-cell hybridomas. These results argue against the hypothesis that E alpha chains are minimally polymorphic because mutations in E alpha are functionally neutral. PMID- 8206534 TI - Hepatitis E virus: epidemiological, clinical and serological studies of north Indian epidemic. AB - BACKGROUND: A large waterborne epidemic of viral hepatitis occurred in the city of Karnal (Haryana) from February to April 1987. An attempt was made to study the epidemic clinically, serologically and etiologically. METHODS: A house-to-house search of the city was conducted for the detection of acute hepatitis cases. Patients willing to give blood samples for liver function tests were studied. RESULTS: A total of 1273 persons (0.79% of persons surveyed) were affected by viral hepatitis. Of the 477 clinically and biochemically documented cases, more than 75% were adults, while only 11% were less than 10 years old. Children below 15 years of age and females had a significantly higher incidence of anicteric hepatitis. Serological markers for acute hepatitis A and B viruses were absent in 85% of patients. Antibodies to hepatitis E virus (HEV) were detected in 84% of acute phase sera studied by indirect immunofluorescence assay. Liver biopsy showed characteristic features of cholangitic hepatitis. Three of 19 pregnant females who developed hepatitis died. No residual clinical or biochemical abnormality was detected in any of the patients followed up for 8 months. This epidemic correlated with the timing of unsupervised digging of lanes to provide new tap water connections to houses in the congested area of the city. This resulted in damage to the sewerage system and leakages which contaminated drinking water supply. CONCLUSION: HEV was transmitted by contaminated drinking water in this epidemic. Most affected individuals were adults, and recovered without sequelae. Affected pregnant women had a worse outcome. PMID- 8206535 TI - Current practice in biliary surgery: the Indian scenario. AB - OBJECTIVE: Documentation of current biliary surgical practices of surgeons in India. METHODS: A postal questionnaire survey of the consultants in surgery in all the medical colleges in India was done to establish their current practice regarding cholecystectomy and to assess the influence of recent studies on their practice. RESULTS: The response rate was 23% (264/1127). About half of the surgeons did both ultrasonography and oral cholecystography for the diagnosis of cholelithiasis. Acute cholecystitis was managed conservatively by 80% of surgeons. Antibiotics were used by all surgeons but 87% of them used antibiotics for more than one day. Peroperative cholangiography was done in all cases by 20% of those who had the facilities available. Incidental appendectomy was done by 26% of surgeons. Drain was used in all cases by 78% of surgeons. Patients were discharged after suture removal by 77% of surgeons. CONCLUSIONS: The practices of the Indian surgeon surveyed were against the recommendations in current literature which did not seem to have had much impact on them regarding their practice of biliary surgery. PMID- 8206536 TI - Laparoscopic cholecystectomy: analysis of 100 cases. AB - OBJECTIVE: To study the efficacy and safety of laparoscopic cholecystectomy. METHODS: One hundred patients with symptomatic cholelithiasis were subjected to laparoscopic cholecystectomy. Preoperative ERCP and sphincterotomy were performed to detect and treat patients suspected to have associated common bile duct (CBD) stones on clinical, biochemical and imaging methods. RESULTS: Ninety patients underwent successful laparoscopic cholecystectomy. The mean operating time was 90 minutes. There were no deaths and morbidity was minimal (6%). Eighty five patients were discharged within 48 hours of surgery. In ten patients the procedure was converted to open surgery. Previous upper abdominal surgery; associated CBD stones; empyema gall bladder; and shrunken, non distensible gall bladder could make the laparoscopic procedure difficult and forewarn the surgeon about a possible conversion to open surgery. CONCLUSION: Laparoscopic cholecystectomy is a safe and effective method of gall bladder removal. PMID- 8206537 TI - Platelet serotonin uptake in duodenal ulcer patients. AB - Platelet serotonin uptake was measured in 10 duodenal ulcer patients and 10 controls by determining the concentration of radioactivity in platelets after incubation with tritium-labelled serotonin binoxalate. Platelet 5-HT uptake in ulcer patients (312.0 +/- 125.0 CPM/10(7) platelets) was significantly higher than that in the control group (186.0 +/- 53.0 CPM/10(7) platelets; p < 0.01). Since the kinetics of 5-HT uptake by platelets may be a reflector of enhanced serotonergic activity, this finding may have implications in future therapeutic strategies for this disease. PMID- 8206538 TI - Value of clinico-psychiatric assessment in the diagnosis of chronic intractable pain in abdomen. AB - To evaluate the role of psychiatric illness in patients with chronic abdominal pain, 50 patients with this symptom were subjected to thorough clinical examination, detailed investigations and Goldberg's 60-item General Health Questionnaire. Those scoring 12 in this questionnaire were subjected to a detailed psychiatric evaluation. Sixteen (32%) patients had pure organic illnesses, 8 (16%) had organic illness with associated psychiatric factors and 26 (52%) had definite psychiatric illness. We conclude that chronic abdominal pain is often associated with psychiatric illness. PMID- 8206539 TI - Manometric analysis of the pharyngo-esophageal segment. AB - Manometry of the pharyngo-esophageal segment can be a valuable tool in the investigation of pharyngeal dysphagia. Advances in technology have overcome previous equipment shortcomings and now allow accurate measurements of such factors as the rapid response rate of the striated muscle and asymmetry of the upper esophageal sphincter. Close attention to technique can overcome difficulties with movement artifacts encountered during deglutition. There are an increasing number of reports in the literature of manometric studies of normal swallow function as well as of patients with oropharyngeal dysphagia. PMID- 8206540 TI - Genetic hemochromatosis presenting as asymptomatic hepatomegaly. AB - A case of genetic hemochromatosis presented with asymptomatic hepatomegaly. The diagnosis was based on elevated serum iron, serum ferritin and transferrin saturation, a characteristic picture on magnetic resonance imaging, and liver biopsy showing cirrhosis with excessive iron deposits in the liver parenchyma. The extreme rarity of this disease in our country is perhaps determined by hereditary factors. PMID- 8206541 TI - Bifid pancreas: an endoscopic retrograde pancreaticographic curiosity. AB - Bifid pancreas, representing a major bifurcation of the main pancreatic duct, has rarely been reported. We report four such cases where this condition was picked up incidentally. PMID- 8206542 TI - Primary malignant carcinoid of the esophagus. AB - Primary malignant esophageal carcinoid in a 55-year-old man with lung abscess is reported. The tumor was detected incidentally at autopsy and had metastasized to the posterior mediastinal lymph nodes. PMID- 8206543 TI - Clot cholecystitis. PMID- 8206544 TI - Hodgkin's lymphoma of colon: an unusual cause of isolated splenic vein obstruction. AB - A case of splenic vein obstruction due to infiltration by Hodgkin's lymphoma of the colon is reported. The patient presented with massive upper gastrointestinal hemorrhage and a lump in the abdomen. Laparotomy revealed a colonic tumor infiltrating the splenic vein, causing left sided portal hypertension. PMID- 8206545 TI - Peutz-Jegher's syndrome with polydactyly. PMID- 8206546 TI - More unbridled bureaucracy. PMID- 8206547 TI - Prevalence of altered sensations associated with mandibular implant surgery. PMID- 8206548 TI - Prevalence of altered sensations associated with implant surgery. PMID- 8206549 TI - Torque generated by handheld screwdrivers and mechanical torquing devices for osseointegrated implants. AB - This study evaluated the ability of practitioners experienced in the use of Branemark implant components to impart a desired torque using handheld screwdrivers. The torque output and variability of mechanical torque devices was also examined. For clinicians using handheld screwdrivers, values ranged from 0.7 to 18.1 Ncm, 1.4 to 33.7 Ncm, and 8.2 to 36.2 Ncm for the 10-Ncm, 20-Ncm, and 32 Ncm torques respectively. The manually operated mechanical torquing devices produced torque values within the tolerances specified by their respective manufacturers at all levels. Significant variation from the manufacturer's set values were noted as a function of tightening speed with the electronic torquing device. The data indicate that there is wide variation in the ability of clinicians to perceive adequate torquing forces applied to implant components. Calibrated torquing devices are mandatory if proper torquing procedures are to be accomplished. PMID- 8206550 TI - Effects of subgingival irrigation with chlorhexidine on the periodontal status of patients with HA-coated integral dental implants. AB - The purpose of this study was to examine the effect of chlorhexidine irrigation on the periodontal status of patients with HA-coated dental implants as measured by clinical, microbiological, and immunological measures. Thirty non-adjacent implants were randomly assigned to receive a one-time irrigation with either 0.12% chlorhexidine or sterile saline, or no irrigation. All parameters were measured at baseline, 2, 5, and 8 weeks. Results showed no significant differences between any treatment modalities at any time interval. A statistically significant decrease in probing depth (P < .05) occurred within the chlorhexidine and no-treatment groups at all time intervals compared to baseline. PMID- 8206551 TI - Histochemical and laser scanning microscopy characterization of the hydroxyapatite-bone interface: an experimental study in rabbits. AB - An experimental study was done in rabbits to characterize the bone-hydroxyapatite (HA) interface by the use of histochemical staining for mineralized tissue and laser scanning microscopy (LSM) on undemineralized sections. Twenty HA-coated Sustain implants were placed in rabbit femurs and retrieved after 6 months. The specimens were then processed to obtain thin ground sections. In all specimens, there was intimate contact between bone and HA. In some portions, mineralized bone was in tight, direct contact with the HA, while in other portions, a basophilic unmineralized material was present between bone and HA. This material was thicker in areas with active bone formation upon the HA surface and had staining characteristics similar to the material present around the osteocyte lacunae. LSM showed a fluorescence present in many areas of the interface, in osteocyte lacunae, and inside the coating. An organic bonding between bone and HA can probably be hypothesized. PMID- 8206552 TI - Loose gold screws frequently occur in full-arch fixed prostheses supported by osseointegrated implants after 5 years. AB - The possible occurrence of loose gold and abutment screws retaining full-arch osseointegrated prostheses has been investigated. The prostheses had been in use for at least 5 years. The findings were related to clinical parameters such as accuracy of the superstructure, operator dependence, and clinical and radiological diagnosis of implant status after 5 years. The principles of the California Dental Association's (CDA) quality evaluation criteria were modified and applied in the study. Gold screw loosening was found to be related to framework misfit and was considered to be operator dependent to some extent. It is recommended that full-arch fixed prostheses be retightened after 5 years. PMID- 8206553 TI - Clinical evaluation of single-tooth restorations supported by osseointegrated implants: a retrospective study. AB - This retrospective study of Branemark implants presents results from 93 implants for single-tooth replacements placed in 77 patients from 1987 to 1990. Only two implants were lost: one before the abutment operation and one during the first year in function. Patients' reactions to the rehabilitations were very positive regarding esthetic aspects and function. The most obvious problem was related to loose abutment screws. Forty-three percent of the abutment screws had to be retightened during the follow-up period, and for this reason, nine cemented crowns had to be remade. PMID- 8206554 TI - Implant-supported maxillary overdentures: outcome in planned and emergency cases. AB - At the Postgraduate Dental Education Center, Orebro, Sweden, maxillary implant supported overdentures have mainly been used in either planned cases (where implants sufficient for a fixed prosthesis could not be placed) or emergency cases (originally planned for a fixed restoration but where implants lost during the healing period made such treatment impossible). Twenty-five cases were studied retrospectively. In the planned group, only two of 19 patients had lost an implant during the follow-up period with overdentures; in the emergency group, four subjects of six lost implant(s) during the same period. The total loss of implants during healing and overdenture function was 7% in the planned group and 72% in the emergency group. The curves for survival of overdentures without loss of supporting implants were significantly different (P = .00) for the planned group and the emergency group. PMID- 8206555 TI - Complications and maintenance requirements for fixed prostheses and overdentures in the edentulous mandible: a 5-year report. AB - Overdentures and fixed prostheses were consecutively placed into 50 edentulous mandibles and were followed for 5 years. During this period of follow-up, 25 overdentures were supported by 68 implants with a success rate of 92.65%, and 25 fixed restorations were supported by 132 implants with a success rate of 90.15%. Postinsertion adjustment in the first year was more common for the overdentures. Thereafter, fixed prostheses had more complications and required more maintenance than overdentures, the average number of recalls per year being 2.27 and 1.57 respectively. The main complications were associated with the peri-implant mucosa, abutment and gold screws, acrylic-resin components, and retentive clips. Overdentures offer an attractive alternative to fixed prostheses in the treatment of the edentulous mandible. PMID- 8206556 TI - Evaluation of the peri-implant epithelial tissue of percutaneous implant abutments supporting maxillofacial prostheses. AB - The use of commercially pure titanium endosseous implants has become state-of-the art treatment for patients with craniofacial defects. This study defined criteria that can be used in assessing the peri-implant abutment epithelium. The criteria were then used to examine overall tissue reaction. In this investigation, seven patients with percutaneous craniofacial implants were evaluated. Two of these patients exhibited adverse skin reactions that were associated with heavy sebaceous crusting, skin cultures positive for Staphylococcus aureus, higher Periotest values, and thicker peri-abutment tissue with greater mobility. It was determined that these factors can predispose the patient to local infection, which, if ignored, can result in failure of the implant. This study indicates that adequate patient hygiene is crucial to maintaining healthy tissues in the peri-implant abutment site. PMID- 8206558 TI - Radiographic analysis of a two-piece apatite implant: Part II. Preliminary report of 2-year observation. AB - Marginal bone height and bone density were evaluated for 2 years after two-piece dense hydroxyapatite implant (Apaceram) placement using standardized radiography and digital image processing. The chronological changes in marginal bone height were divided into three groups: Group I-level was constant or became higher with time; Group II-bone decreased gradually after superstructure placement; and Group III-bone decreased in height rapidly after abutment placement. Bone density around the successful Apaceram implant, especially in the crestal region, increased clearly. The results suggest that bone resorption/formation around the implant is related to occlusal stress, and that adequate occlusal stress should be exerted on the implant at each phase after the implant placement. PMID- 8206557 TI - Changes in chewing patterns after implantation in the edentulous mandible. AB - Almost all edentulous patients with implant-supported prostheses in mandibles describe an improvement in their chewing function and quality of life. This was reason to believe that an implant prosthetic treatment actually influences mandibular border movements, as well as the chewing patterns. The present study compares border movements and chewing patterns in 15 patients recorded with the Sirognathograph. The first measurements were made with existing complete dentures. After implantation and rehabilitation with a Dolder-bar and clip-to-bar overdenture, the movements were recorded again. The measurements revealed an improved guidance of the mandibular movements and larger borderline patterns following stabilization of the complete denture with the bar. This leads to more harmonic shapes in the movements and better chewing efficiency. PMID- 8206559 TI - Explanation procedure with special emphasis on the ITI implant system. AB - Removal of implants is performed in cases of irreversible implant failure and in patients having psychological problems with implants. The explantation procedure can be complicated in some situations. In the present article, techniques of explantation and some related considerations are presented. PMID- 8206560 TI - The use of attachments in combination implant and natural-tooth fixed partial dentures: a technical report. AB - When implants and natural teeth are combined, forces on the abutments need to be controlled so that neither the teeth nor the implants sustain excessive amounts of force. The technique described addresses reduction of potentially harmful cantilever effects in a fixed prosthesis that is facultatively removable. A nonrigid attachment is used in the implant crown. Telescopic copings are definitively cemented on the natural teeth. Provisionally cemented overcastings incorporate this nonrigid connection between the pontics and the implant crowns. The means of connection employs a semiprecision attachment in which the female connector is placed within the relatively immobile implant crown. The male connector is placed on the pontic seating into the implant crown. This relationship limits cantilever forces exerted on the natural-tooth abutment. The nonrigid connection of the tooth-supported retainer limits cantilever forces and directs occlusal loads axially in a direction along the long axis of the implant. This arrangement is acceptable as compared to the complete tooth-supported arrangement described by Shillingburg; in this situation, the implant will not migrate. Since 1986, this arrangement has been used clinically without attachment migrations, implant failure, or endodontic therapy, with only minor screw loosening episodes. PMID- 8206561 TI - Alternative restorative techniques of the CeraOne single-tooth abutment: a technical note. AB - The screw-joint stability of single-tooth implant-supported restorations has been shown to be significantly improved with an abutment system (CeraOne) that uses a gold-alloy screw tightened at a prescribed amount of torque. The abutment system requires the cementation of the restoration to the abutment. This negates the possibility of accessing the abutment screw when the removal of the restoration is desired. This article described two alternative restorative techniques to maintain accessibility to the screw joint. PMID- 8206562 TI - Does the risk of complication make transpositioning the inferior alveolar nerve in conjunction with implant placement a "last resort" surgical procedure? PMID- 8206563 TI - Elevated serum insulin levels in patients with essential hypertension and microalbuminuria. AB - Hyperinsulinemia, insulin resistance, or both have been described in patients with essential hypertension. Previous work from our laboratory has shown that in hypertensive patients with microalbuminuria, dyslipidemia and abnormal patterns in the diurnal variations of blood pressure are frequently associated. Whether hyperinsulinemia and microalbuminuria are directly related has not been determined. To test this possibility, we measured the plasma insulin response to an oral glucose load in 25 patients with or without microalbuminuria and 20 normotensive control subjects. Serum lipid profile and 24-hour ambulatory blood pressure were obtained. In the hypertensive patients as a group, the plasma insulin response to glucose (evaluated as the insulin area under the curve) was significantly enhanced compared with a group of 20 normotensive healthy control subjects (46,311 +/- 3745 and 27,557 +/- 2563 pmol/L x 2 hours, P < .01). When the hypertensive patients were subdivided according to their albumin excretion rate, the microalbuminuric patients had significantly higher plasma glucose (969 +/- 45.2 versus 762 +/- 28.7 mmol/L x 2 hours, P < .01) and insulin (59,172 +/- 5964 versus 37,737 +/- 3422 pmol/L x 2 hours, P < .01) area under the curve values. In addition, a significant direct correlation was found to exist between insulin area under the curve and the urinary albumin excretion rate (r = .63, P < .001). Serum levels of lipoprotein(a) were significantly greater (P < .01) in patients with than in those without microalbuminuria and in control subjects. Furthermore, daytime diastolic blood pressure and nighttime systolic and diastolic blood pressure values were greater in patients with than in those without microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206564 TI - Glucose and insulin levels during diuretic therapy in hypertensive men. AB - We investigated serum glucose and insulin levels resulting from thiazide or thiazide-like diuretic administration and determined whether they were associated with serum or intracellular potassium or magnesium values. We also explored the role of obesity both alone and with thiazides on serum insulin and glucose. Hypertensive men were withdrawn from diuretics and repleted with oral potassium and magnesium and then randomized to 2 months of treatment with (1) hydrochlorothiazide, (2) hydrochlorothiazide with oral potassium, (3) hydrochlorothiazide with oral potassium and magnesium (4) hydrochlorothiazide and triamterene, (5) chlorthalidone, or (6) placebo. Serum was available from 202 participants for insulin and glucose determinations. Mean fasting serum glucose and insulin did not change significantly after 2 months of randomized therapy with the exception of participants randomized to chlorthalidone, who had significant increases in both serum insulin and glucose (P < .05 and P < .01, respectively). As body mass index increased, there was a corresponding increase in serum insulin and to a lesser degree in serum glucose. Also, as body mass index increased, participants taking hydrochlorothiazide had a corresponding increase of serum insulin (P < .05). After treatment, intracellular potassium and magnesium were both associated with higher serum insulin (P < .001 for each), and serum potassium was associated with higher and serum magnesium with lower serum glucose (P < .01 for each). In most hypertensive men, treatment with 50 mg chlorthalidone increases glucose and insulin levels, whereas administration of 50 mg hydrochlorothiazide, with or without potassium and/or magnesium conserving strategies, does not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206565 TI - Hypocalcemia and pregnancy-induced hypertension produced by low-calcium diet. AB - Recent studies from our laboratory in fasting pregnant ewes with twin gestation have implicated low serum calcium concentration in the etiology of hypertension in pregnancy. We hypothesized that the reduction in serum calcium concentration produced by feeding of a calcium-deficient diet in twin gestation would lead to a significant increase in maternal arterial blood pressure, vascular resistance, and protein in the urine and decreased uterine blood flow. Twenty-five instrumented ewes were used in the present study. After surgery a calcium deficient diet and deionized water (calcium ion free) were provided ad libitum to 19 animals. Blood pressure, cardiac output, heart rate, and uterine blood flow were monitored every other day. Six control animals were provided with standard Rumilab diet and tap water (group 1). Animals on a low-calcium diet (group 2) were subdivided according to the blood ionized calcium response to low dietary calcium intake. Non-hypocalcemic animals were assigned to group 2a (n = 10), and hypocalcemic animals (calcium concentration below two standard deviations from the control group) were assigned to group 2b (n = 9). In group 2b calcium concentration decreased from 1.03 +/- 0.04 mmol/L on day 110 of gestation to 0.77 +/- 0.03 mmol/L by day 125 of gestation. Arterial blood pressure increased significantly from 76 +/- 2 to 91 +/- 2 mm Hg, and uterine blood flow decreased from 950 +/- 53 to 579 +/- 48 mL/min. Urinary protein increased from 1.7 +/- 0.3 to 10.5 +/- 1.2 g/L.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206566 TI - Blood pressure inversely correlates with thrombin-evoked calcium rise in platelets. AB - Earlier investigations showed a positive correlation between basal cytosolic free calcium in human platelets and blood pressure; however, recent studies have failed to show this relation. We undertook the present work to examine which platelet cytosolic calcium parameters (namely, cytosolic calcium in resting or stimulated states in calcium-containing and calcium-free media) present the least variability and best correlation with blood pressure. We studied 17 healthy white men on three different occasions separated by 1- and 4-week intervals. Their manual and ambulatory automated 24-hour blood pressure measurements were correlated with cytosolic calcium in resting and stimulated (thrombin-treated) fura 2-loaded platelets. The following cytosolic calcium parameters were measured in 1 mmol/L calcium and calcium-free media: basal cytosolic calcium, peak thrombin-evoked cytosolic calcium, and post-transient cytosolic calcium 5 minutes after thrombin treatment. The highest and lowest coefficients of variation were respectively shown by the basal cytosolic calcium (22.8%) and peak thrombin evoked cytosolic calcium (10.1%) in calcium medium. Basal cytosolic calcium did not correlate with any of the blood pressure parameters. Of the cytosolic calcium parameters, peak thrombin-evoked cytosolic calcium in calcium medium demonstrated consistent (negative) correlations with blood pressure, with better correlations shown with diastolic than systolic blood pressure of both automated and manual blood pressure readings. Peak thrombin-evoked cytosolic calcium in calcium medium showed similar correlations with nighttime and daytime automated blood pressure measurements. There were no correlations between peak thrombin-evoked cytosolic calcium in calcium-free medium and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206567 TI - Calcium dependency of frequency-stimulated atrial natriuretic peptide secretion. AB - In this study we examined the mechanism whereby atrial natriuretic peptide secretion is increased when the frequency of contraction is raised from 2 to 5 Hz. We tested the hypothesis that calcium plays a significant role in the frequency-stimulated response. Using superfused rat left atria, we found that lowering the superfusate calcium concentration from 1.8 to 0.2 mmol/L abolished the frequency-stimulated atrial natriuretic peptide secretory response. Superfusion with ryanodine (1 mumol/L), an inhibitor of sarcoplasmic reticulum calcium release, resulted in a minimal inhibitory effect. Superfusion with 50 mumol/L nitrendipine or 10 mumol/L diltiazem inhibited the frequency-stimulated response by 46% to 48%. The lack of total inhibition suggested that an additional mechanism of calcium influx was involved, namely, inward calcium movement carried by Na(+)-Ca2+ exchange. As intracellular sodium has been reported to rise with an increase in beat frequency, a fall in the sodium gradient would favor inward calcium movement by Na(+)-Ca2+ exchange. Because we could not directly assess the role of Na(+)-Ca2+ exchange in this experimental paradigm, we examined the effect of lowering the transmembrane sodium gradient on atrial natriuretic peptide secretion by superfusion with the sodium channel activator veratridine or the sodium ionophore monensin. Superfusion with 1 mumol/L veratridine increased atrial natriuretic peptide secretion by 2.3-fold, and 1, 5, and 10 mumol/L monensin increased secretion by 1.1-, 2.1-, and 15.7-fold, respectively. In addition, we examined the possibility that the reported rise in intracellular sodium associated with increased beat frequency was due to enhanced Na(+)-H+ antiporter activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206568 TI - Glucose intolerance as a predictor of hypertension in pregnancy. AB - Insulin resistance is associated with and may be causal in essential hypertension, but the relation between insulin resistance and hypertension arising de novo in pregnancy is unclear. Transient hypertension of pregnancy (new onset nonproteinuric hypertension of late pregnancy) is associated with a high risk of later essential hypertension and thus may have similar pathophysiology. To assess the association between glucose intolerance and subsequent development of proteinuric and nonproteinuric hypertension in pregnancy in women without underlying essential hypertension or overt glucose intolerance, we performed a retrospective case-control study comparing glucose levels on routine screening for gestational diabetes mellitus among women subsequently developing hypertension. Women who developed hypertension in pregnancy (n = 97) had significantly higher glucose levels on 50-g oral glucose loading test (P < .01) and a significantly higher frequency of abnormal glucose loading tests (> or = 7.8 mmol/L) (P < .01) than women who remained normotensive (n = 77). Relative glucose intolerance was particularly common in women who developed nonproteinuric hypertension. Women who developed hypertension also had greater prepregnancy body mass index (P < or = .0001) and baseline systolic and diastolic blood pressures (P < or = .0001 for both), although all subjects were normotensive at baseline by study design. However, after adjustment for these and other potential confounders, an abnormal glucose loading test remained a significant predictor of development of hypertension (P < .05) and, specifically, nonproteinuric hypertension in pregnancy (P < .01). Among a subgroup of women in whom insulin levels were also measured (n = 80), there was a nonsignificant trend toward higher insulin levels in women developing hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206569 TI - Altered protein kinase C regulation of phosphoinositide-coupled receptors in deoxycorticosterone acetate-salt hypertensive rats. AB - This study examined the contribution of phosphatidylinositol metabolism and the efficacy of protein kinase C-mediated desensitization in the exaggerated alpha 1b adrenergic receptor-mediated inositol phosphate response in the aorta of the deoxycorticosterone acetate (DOCA)-salt rat model of hypertension. The basal accumulation of inositol phosphates and the basal incorporation of [3H]myo inositol in the phosphatidylinositol lipid pool were significantly higher in the aorta of these hypertensive rats. A positive correlation (r = .88, P < .01) was demonstrated between basal inositol phosphate levels and the [3H]myo-inositol labeled phosphatidylinositol lipid pool. In hypertensive rats, alpha 1b adrenergic receptor-mediated inositol phosphate production in response to phenylephrine was significantly higher compared with normotensive rats. Despite the normalization of phenylephrine-mediated inositol phosphate production to the [3H]myo-inositol-labeled phosphatidylinositol lipid pool, the alpha 1b-adrenergic response remained significantly higher in the hypertensive rats. Phorbol ester activation of protein kinase C attenuated to a lesser extent phenylephrine mediated inositol phosphate production (40%) in the aorta of hypertensive rats compared with the 80% attenuation observed in the aorta of normotensive rats. This desensitization was inhibited in both groups by the protein kinase C inhibitor staurosporine. The blunted desensitization of the alpha 1b-adrenergic receptor by protein kinase C activation was not associated with a decrease in protein kinase C activity in the hypertensive rats, because aortic strips from these animals were more responsive to phorbol ester activation than aortic strips from normotensive animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206570 TI - Body mass index and associations of sodium and potassium with blood pressure in INTERSALT. AB - This report further examines the relation of body mass index (BMI) to associations of 24-hour urinary sodium, potassium, and sodium-potassium ratio with blood pressure in INTERSALT, a 52-center international study of electrolytes and blood pressure. Analyses without adjustment for BMI indicated average systolic pressure greater by 6.00 mm Hg per 100 mmol higher sodium and diastolic by 2.52 mm Hg. With adjustment for BMI, these values were reduced to 3.14 and 0.14 mm Hg, respectively. For the sodium-potassium ratio, blood pressure associations were stronger when not adjusted for BMI, and for potassium, adjustment generally had little effect. To explore possible interactions of these variables with BMI in relation to blood pressure, the 52 centers were divided into two groups of 26 based on whether the center median for BMI was less than or greater than or equal to 24.5 kg/m2, and individuals within each of the 52 centers were classified into lower- or higher-BMI groups based on individual BMI less than or greater than or equal to 24.1 kg/m2. Sodium and the sodium-potassium ratio were positively and significantly and potassium inversely and significantly related to systolic pressure in all four of these subgroups, and the sodium potassium ratio and potassium were related to diastolic pressure in two and three subgroups, respectively. Electrolyte-blood pressure associations did not differ significantly between the two subgroups of centers or between the two subgroups based on individuals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206571 TI - Blood pressure-lowering effect of an orally active vasopressin V1 receptor antagonist in mineralocorticoid hypertension in the rat. AB - We studied the contribution of vasopressin to the maintenance of high blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertension in the rat using the nonpeptide orally effective vasopressin V1 receptor antagonist OPC-21268. Binding kinetic studies demonstrated that oral OPC-21268 (30 mg/kg) acted as a competitive antagonist at the vasopressin V1 receptor in DOCA-salt and salt control rats. Basal mean intra-arterial blood pressure was 140 +/- 4 mm Hg (n = 12) in DOCA-salt rats compared with 111 +/- 2 mm Hg in salt control rats (n = 18). Acute oral OPC-21268 (30 mg/kg) significantly (P < .01) reduced mean intra arterial pressure in DOCA-salt hypertension, with an average maximal decrease of 24 +/- 3 mm Hg occurring at 2.5 +/- 0.7 hours after dosing. Systolic blood pressure (tail-cuff) in DOCA-salt rats was 178 +/- 2 mm Hg. Chronic oral OPC 21268 (30 mg/kg) twice daily for 7 days significantly (P < .01) reduced systolic blood pressure in DOCA-salt hypertension, with an average maximal decrease of 27 +/- 5 mm Hg. The antihypertensive effect was reversed 5 days after treatment with OPC-21268 was stopped. In water control rats basal systolic pressure (120 +/- 1 mm Hg, n = 20) was unchanged by chronic oral OPC-21268 (30 mg/kg twice daily for 7 days), and this was confirmed by direct measurement of mean intra-arterial pressure. After chronic oral OPC-21268 (30 mg/kg twice daily for 7 days) hepatic V1 receptor binding was significantly reduced for up to 10 hours (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206572 TI - Vascular responsiveness to nitric oxide synthesis inhibition in hypertensive rats. AB - We contrasted in normotensive and hypertensive rats the effect of inhibition of nitric oxide synthesis on isometric tension development by aortic rings bathed in Krebs' bicarbonate buffer. NG-Nitro-L-arginine methyl ester (L-NAME) (3 x 10(-4) mol/L) increased tension (82 +/- 11% of the response to 120 mmol/L potassium chloride) in rings of thoracic aorta taken from hypertensive rats 7 to 14 days after aortic coarctation, whereas rings of abdominal aorta from below the coarctation were unresponsive, as were rings of thoracic aorta from rats with deoxycorticosterone-salt-induced hypertension and from the corresponding normotensive controls of either model of hypertension. The contractile response to L-NAME in aortic rings of rats with aortic coarctation was reversed by L arginine (1 mmol/L), attenuated by removal of the endothelium, and blunted by the protein kinase C inhibitor staurosporine but was unaffected by inhibition of cyclooxygenase, scavengers of superoxide anion, or blockade of receptors for angiotensin, norepinephrine, serotonin, or endothelin. In additional experiments we contrasted the effect of L-NAME (10 mg/kg IV) on the blood pressure of sham operated rats and rats with aortic coarctation after pretreatment of animals in both groups with DuP 753 (30 mg/kg IV) to achieve blood pressure equalization. The pressor response to L-NAME was twofold greater in rats with aortic coarctation than in sham-operated controls. That pressor and aortic constrictor responsiveness to L-NAME are increased after aortic coarctation suggests that a mechanism of vasodilation, mediated by nitric oxide, is preferentially manifested in rats with aortic coarctation-induced hypertension. PMID- 8206573 TI - Long-term administration of L-arginine improves nitric oxide release from kidney in deoxycorticosterone acetate-salt hypertensive rats. AB - To examine the effects of L-arginine (L-Arg) on endothelial function, we administered 0.5 g/L L-Arg in drinking water to deoxycorticosterone acetate (DOCA)-salt rats for 8 weeks and then measured nitric oxide (NO) release from isolated kidneys using a newly developed real-time chemiluminescence method. Renal pathology was also analyzed. Acetylcholine caused much smaller declines in renal perfusion pressure (10(-7) mol/L acetylcholine: -24 +/- 2% [SEM] versus -50 +/- 2%, P < .001) and NO release in DOCA-salt rats (+3 +/- 1 versus +33 +/- 3 fmol/min per gram kidney weight, P < .001) compared with control rats. L-Arg did not influence the time course of systolic blood pressure elevation in DOCA-salt rats (211 +/- 5 versus 208 +/- 6 mmHg, DOCA versus L-Arg/DOCA, P = NS). However, oral administration of L-Arg improved acetylcholine-induced declines in renal perfusion pressure (10(-7) mol/L acetylcholine: L-Arg/DOCA, -39 +/- 3%, P < .01 versus DOCA). This change was associated with an increase in NO release by acetylcholine (10(-7) mol/L acetylcholine: L-Arg/DOCA, +10 +/- 1 fmol/min per gram kidney weight, P < .05 versus DOCA). However, morphological changes in renal vessels and glomeruli were similar between DOCA and L-Arg/DOCA rats. These results suggest that L-Arg administration partially reverses renal endothelial function with respect to vasorelaxation and NO release independent of blood pressure changes, indicating that hypertensive vessels seem to be depleted of L Arg and/or have defects in the availability of L-Arg for NO synthesis. PMID- 8206574 TI - Active and passive arteriolar regulation in spontaneously hypertensive rats. AB - This study determined to what extent active and passive wall tensions increase in in vivo intestinal arterioles of 13- to 15-week-old and 25- to 27-week-old spontaneously hypertensive rats (SHR) to maintain normal or smaller arteriolar diameters during microvascular hypertension. Acetylcholine and nitroprusside were used to determine whether vascular muscle relaxation to endothelium-derived relaxing factor or cyclic GMP is impaired. Large arterioles of hypertensive rats have passive tension-circumference relations that are steeper and shifted to the left compared with those of age-matched controls; passive resistance to distension limits vasodilation in hypertensive rats except at their naturally elevated arteriolar pressure. Passive tension contributes approximately 30% of the total resting tension in arterioles of hypertensive and normotensive rats because a greater passive tension occurs at the 20% to 25% constricted resting diameter in hypertensive rats. Absolute and relative changes in the diameter of SHR arterioles during acetylcholine and nitroprusside application were equal to or greater than those in Wistar-Kyoto rats. However, reduction in active tension was suppressed in older SHR and remained approximately 50% higher than that found in older Wistar-Kyoto rats during drug application. Vasoconstriction and increased passive resistance to distension of the arteriolar wall diminish the active tension required to maintain normal or smaller resting diameters against microvascular hypertension. However, the elevated microvascular pressure in hypertensive rats is required to allow near-normal dilation to compensate for their increased passive resistance to stretch and decreased ability to relax active tension through cyclic GMP mechanisms. PMID- 8206575 TI - Hypertension induced by brain grafts from fetal spontaneously hypertensive rats. AB - Hypothalami from fetal rats were grafted into the third ventricle of four strains of adult rats. Grafts from spontaneously hypertensive rats (SHR), in contrast to grafts from Wistar-Kyoto (WKY) rats, induced an elevation of systolic blood pressure and a thickening of the media of resistance arteries, along with corresponding alterations in the contractile properties of these vessels. However, no cardiac hypertrophy was observed. The resistance arteries of rats grafted with hypothalamic from SHR also displayed functional alterations that were similar to what is typically found in the resistance arteries of young prehypertensive SHR, ie, an increase in the sensitivity to cocaine and an impairment in the ability to relax in the presence of acetylcholine. This suggests that the brain may play a causal role in these alterations. Histological examination of sections of brains grafted with previously labeled tissue revealed that (1) there was no brain area that was systematically infiltrated by grafts from SHR and not by grafts from WKY rats; (2) the volume of the transplants appeared larger 2 weeks after the graft than the volume of the tissue originally implanted; and (3) grafts from SHR were slightly larger, displayed more individual foci, and extended farther along the anteroposterior axis than grafts from WKY rats. In addition, glial cultures derived from the hypothalami of SHR had a higher in vitro growth rate than equivalent cultures from WKY rats. It is therefore possible that the ability of brain grafts from SHR to induce hypertension is related to a higher proliferative and/or migratory potential of nonneuronal cells within the hypothalamus. PMID- 8206576 TI - Effects of lateral parabrachial nucleus lesions in chronic renal hypertensive rats. AB - Neuroanatomic studies describing forebrain projections to the lateral parabrachial nucleus suggest a central integrative role in cardiovascular regulation. We performed this study to examine the role of this pontine nucleus in the maintenance of one-kidney, figure-8 renal-wrap hypertension. Bilateral ibotenic acid ablation of the lateral parabrachial nucleus was performed 4 weeks after induction of hypertension or sham operation. In hypertensive rats, ablation produced a significant reduction in mean arterial pressure from 160 +/- 4 to 118 +/- 2 mm Hg and a transient but significant increase in heart rate from 381 +/- 5 to 408 +/- 8 beats per minute on the first day after ablation; arterial pressure returned to preablation values by day 5 after ablation. In sham-operated, normotensive animals, arterial pressure was not altered by ablation, and a transient but significant increase in heart rate from 384 +/- 8 to 419 +/- 7 beats per minute was again observed. Before ablation, trimethaphan administration produced a significantly greater drop in arterial pressure in hypertensive (delta 72.8 +/- 4.6 mm Hg) versus normotensive (delta-55.7 +/- 4.1 mm Hg) animals. This effect was eliminated on day 1 after ablation yet returned on day 4 after ablation. In blood samples obtained before ablation and on days 1 and 4 after ablation, circulating plasma catecholamine concentrations in both groups remained unchanged. These observations suggest that, because of possible alternate neural compensatory mechanisms, lateral parabrachial nucleus ablation produces a significant yet transient reversal of renal-wrap hypertension. Thus, the lateral parabrachial nucleus may contribute to the increased sympathetic nervous system function associated with this model. PMID- 8206577 TI - Inhibition of angiotensin-converting enzyme modulates the autoregulation of regional cerebral blood flow in hypertensive rats. AB - The inhibition of angiotensin-converting enzyme activities is considered to favorably modulate the hemodynamics of the brain. We designed the present study to examine the effects of angiotensin-converting enzyme inhibitors on regional differences in the lower limits of cerebral blood flow autoregulation in spontaneously hypertensive rats. Angiotensin-converting enzyme inhibitors (either 10 mg/kg captopril or SQ 29,852 in saline) were intravenously injected 15 minutes before hemorrhagic hypotension was induced. Cerebral blood flows to the parietal cortex and thalamus were simultaneously measured by hydrogen clearance. Both captopril and SQ 29,852 significantly decreased mean arterial pressure by 14 to 18 mm Hg and also reduced calculated cerebral vascular resistance by 11% to 15% of resting values, which resulted in a well-maintained cerebral blood flow. The lower limits of autoregulation were 76 +/- 2% (mean +/- SEM) and 77 +/- 2% of resting values in the cortex and thalamus, respectively, in control rats. Administration of either captopril or SQ 29,852 significantly reduced the lower limits to 65 +/- 3% (P < .01 versus control) and 67 +/- 2% (P < .05), respectively, in the cortex, which were slightly but always larger than the 71 +/ 3% and 71 +/- 2% reduction, respectively, in the thalamus. The inhibition of angiotensin-converting enzyme activities thus may be more protective against acute hypotension for cerebral microcirculation in the cortex than in the thalamus. PMID- 8206578 TI - Genetic contamination of Dahl SS/Jr rats. Impact on studies of salt-sensitive hypertension. AB - The Dahl salt-sensitive rat (SS/Jr) is a widely used animal model of salt sensitive hypertension. SS/Jr rats are believed to be highly inbred and uniformly sensitive to the hypertensinogenic effects of sodium chloride, but we have recently observed that SS/Jr rats from Harlan Sprague Dawley, Inc, exhibit considerable variability in their blood pressure response to supplemental dietary salt. To test the possibility that commercially available SS/Jr rats are genetically contaminated and therefore no longer fully inbred, we performed molecular genetic studies and blood pressure measurements in several groups of SS/Jr rats purchased from Harlan Sprague Dawley. We found molecular evidence of heterozygosity and/or atypical allelic variants involving loci on at least five different chromosomes. Many of the rats also failed to exhibit a salt-sensitive blood pressure phenotype. We conclude that SS/Jr rats being sold by the only commercial vendor of Dahl rats in the United States are genetically contaminated and resistant to the hypertensinogenic effects of salt. These findings raise serious questions about the interpretation of research conducted with SS/Jr rats obtained from Harlan Sprague Dawley. PMID- 8206579 TI - Salt-induced hypertension in normotensive spontaneously hypertensive rats. AB - Lifetime treatment with oral captopril prevents the development of hypertension in spontaneously hypertensive rats (SHR). We tested the hypothesis that this treatment also prevents the hypertensive response that occurs when untreated NaCl sensitive SHR are placed on a high NaCl diet. Female SHR were continuously treated with oral captopril before conception and throughout lactation, and the offspring were similarly treated with oral captopril throughout life. At 6 weeks of age, treated male SHR were placed on an 8% (or remained on a 1%) NaCl diet, and systolic arterial pressure, heart rate, and body weight were monitored for 2 weeks. The 8% NaCl diet caused a rapid increase in arterial pressure in the lifetime captopril-treated rats, and 18 days after the initiation of the diet, the mean arterial pressure of this group was 136 +/- 7 mm Hg compared with 100 +/ 2 mm Hg in the 1% NaCl diet rats. The results of a second experiment confirmed the hypertensive effect of the high NaCl diet in lifetime captopril-treated SHR and demonstrated that after 18 days on the diet the dietary NaCl-induced hypertensive response was greater in magnitude in lifetime captopril-treated compared with untreated SHR. The results also demonstrated that lifetime captopril-treated Wistar-Kyoto rats, which are normotensive irrespective of captopril treatment, display no significant increase in arterial pressure when given a high NaCl diet. A third experiment demonstrated that rapidly progressing NaCl sensitivity is also present in female lifetime captopril-treated SHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206580 TI - Cardiac and arterial hypertrophy and atherosclerosis in hypertension. AB - Clinical evaluation of the hypertensive patient has traditionally relied on physician measurement of blood pressure and assessment of target-organ involvement by simple laboratory tests. However, this approach is limited in its ability to identify individual patients at high or low risk of complications. In recent years, noninvasive methods have been developed to identify pathological transformations of the heart and arteries that collectively comprise "preclinical hypertensive disease." Measurements by echocardiogram or other methods of left ventricular mass and relative wall thickness identify a spectrum of cardiac adaptations to hypertension, including concentric and eccentric hypertrophy, the recently described pattern of "concentric left ventricular remodeling" (normal mass but increased relative wall thickness), and normal ventricular geometry. In clinical studies, each anatomic pattern is associated with a distinct profile of resting hemodynamics, ambulatory blood pressure, myocardial contractility, and risk of adverse outcomes. Ultrasonic imaging of the carotid or other arteries makes it possible to detect increased arterial wall thickness and discrete atheromas noninvasively. Carotid wall thickness and lumen diameter parallel similar ventricular dimensions in normotensive and hypertensive humans, indicating the presence of integrated patterns of cardiac and vascular adaptation to hypertension. Furthermore, peripheral atherosclerosis is associated with higher ventricular mass and a more adverse 24-hour blood pressure profile. In summary, noninvasive visualization of the heart and blood vessels reveals a spectrum of patterns of anatomic and functional adaptations that are related to the pathophysiology and prognosis of hypertension. PMID- 8206581 TI - Stimulation of the kallikrein-kinin system by pregnancy may help restore renal vasodilator response to glycine in Dahl salt-sensitive rats. PMID- 8206582 TI - Role of glucose intolerance in cardiac diastolic function in essential hypertension. AB - Insulin resistance and glucose intolerance have been suggested to be involved in the pathogenesis of various cardiovascular diseases. We examined the role of glucose intolerance in cardiac performance and cardiac hypertrophy in 33 patients with essential hypertension (28 to 71 years of age, mean +/- SD: 53 +/- 13 years) who had never been treated. Patients with obesity (body mass index > 30 kg/m2) or overt diabetes were excluded. Plasma glucose and insulin were measured after oral administration of 75 g glucose. The incremental areas of glucose and insulin were used as indices of glucose intolerance and insulin resistance, respectively. Patients with impaired glucose tolerance according to World Health Organization criteria (n = 12) showed a significantly higher ratio of peak velocity during atrial contraction to early left ventricular filling phase (A/E ratio) than those with normal glucose tolerance (n = 21) despite similar age, blood pressure, and left ventricular mass index. By regression analysis, left ventricular mass index positively correlated with systolic blood pressure (r = .392, P < .05) but not with any parameters of glucose and insulin metabolism. A/E ratio determined by a Doppler system significantly correlated with age ( r = .776) and fasting and peak levels and incremental area of plasma glucose (r = .529, r = .468, and r = .634) but not with those parameters of insulin. In contrast, ejection fraction was not related to blood pressure, glucose tolerance, or insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206583 TI - Vasoconstriction with norepinephrine causes less forearm insulin resistance than a reflex sympathetic vasoconstriction. AB - We used the insulin-perfused human forearm model to assess the effects of vasoconstriction induced with norepinephrine on the extraction of glucose in the forearm in two groups of healthy young volunteers. The norepinephrine findings were compared with a previously studied group in which vasoconstriction has been caused by reflex activation of the sympathetic nervous system. The aim of the study was to determine the relative importance of hemodynamic and receptor mediated mechanisms of insulin resistance. Plasma insulin, arterial and venous glucose samples, and forearm blood flow were measured at 10-minute intervals during a 30-minute baseline, a 60-minute intra-arterial insulin infusion, and during 30 minutes of insulin infusion plus vasoconstriction. Group 1 (n = 14) had physiological vasoconstriction induced by inflation of bilateral thigh cuffs to 40 mm Hg to cause pooling of blood in the lower extremities and reflex vasoconstriction in the forearm; group 2 (n = 8) had intra-arterial infusion of norepinephrine to achieve the same degree of vasoconstriction as seen with inflation of thigh cuffs in group 1. Subjects in group 3 (n = 7) had infusion of intra-arterial norepinephrine to achieve a twofold increase in physiological vasoconstriction. With a physiological decrease in forearm blood flow (group 1), there was a 19% decrease in forearm blood flow resulting in a 23% reduction in glucose uptake in the forearm (P < .03). The same degree of reduction in forearm blood flow with a predominantly alpha-adrenergic agonist, norepinephrine (group 2), causes much less insulin resistance (a decrease in utilization of 13%) (P < .04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206584 TI - Chronic insulin administration elevates blood pressure in rats. AB - To examine the relative contribution of dietary glucose and infused insulin on blood pressure, we administered a 4% glucose supplement (in drinking water) with and without insulin infusion (15.8 nmol [2.2 U]/d via osmotic minipump) to male Sprague-Dawley rats (n = 6). We also tested the effect of the sympatholytic agent clonidine on rats receiving glucose and insulin. Blood pressure and heart rate were recorded via a novel radio telemetry system. Experiments were performed using a crossover design with three animals receiving treatment and three receiving vehicle for 10 days. After a 10-day washout period, the groups were reversed, and the experiment was repeated. Blood samples for insulin and glucose were drawn throughout the study. Systolic and diastolic blood pressures increased (by 6.0 +/- 1.2 and 2.2 +/- 1.3 mm Hg, respectively) in the animals given glucose alone in association with an increase in plasma insulin. However, blood pressure increased more rapidly and to a greater extent, systolic by 8.6 +/- 0.7 mm Hg and diastolic by 2.9 +/- 1.1 mm Hg, during the insulin treatment that raised plasma insulin above the levels observed during glucose feeding alone. Heart rate increased equally during both treatments. The average change in blood pressure and average plasma insulin during the infusion were correlated (r = .72, P = .009). Blood pressure dropped during the week following discontinuation of the insulin infusion. On rechallenge with insulin and glucose, blood pressure again rose and then decreased after termination of the insulin and glucose administration. Clonidine prevented the rise in blood pressure and heart rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206585 TI - Is microalbuminuria a marker of early intrarenal vascular dysfunction in essential hypertension? AB - The relation between basal intrarenal hemodynamics and the renal response to acute inhibition of angiotensin-converting enzyme by captopril and albuminuria was assessed in 106 lean patients with essential hypertension without detectable proteinuria. It was observed that the microalbuminuric group (24.5% of the total population) was characterized by a higher systemic arterial pressure, a lower level of high-density lipoprotein cholesterol, and similar mean values of age, duration of hypertension, glomerular filtration rate, renal plasma flow, filtration fraction, and plasma renin activity when compared with normoalbuminuric subjects. In response to captopril, a significant renal vasodilatation without a change in glomerular filtration rate or a fall in filtration fraction was observed in normoalbuminuric patients only. In contrast, the renal vasodilator response was abolished in microalbuminuric subjects, together with blunting of the rise in plasma renin activity associated with captopril. This occurred despite similar indexes of activity of the endogenous renin-angiotensin system. It is suggested that microalbuminuria may be a marker of early functional or fixed intrarenal vascular dysfunction in never-treated lean patients with essential hypertension. PMID- 8206586 TI - Cell growth and Na-K-Cl cotransport responses of vascular smooth muscle cells of Milan rats. AB - The present study examines the role of serum growth factors in the proliferative response and Na-K-Cl cotransport activity of vascular smooth muscle cells from Milan normotensive (MNS) and hypertensive (MHS) rats. Cells from thoracic aorta of both strains were cultured in 10% serum medium and made quiescent by 72 hours in 0.3% serum medium. MHS cells grown with 10% serum had a shorter population doubling time than MNS cells between passages 8 and 12 (13.8 +/- 1.7 versus 20.1 +/- 1.6 hours, P < .01, n = 4). MHS cells also exhibited a higher response of thymidine incorporation into nucleic acid to serum, epidermal, and platelet derived growth factor BB. In MHS cells epidermal (100 ng/mL) and platelet (50 ng/mL) growth factors increased thymidine incorporation 2- and 10-fold, respectively. In MNS cells epidermal factor did not induce a significant response, and that of platelet factor was twofold lower than in MHS cells. Binding curves revealed a higher number of receptors for platelet than epidermal growth factor in both strains and a similar number of both receptors in MHS and MNS cells. Quantitative immunoblots of these receptor proteins confirmed the observation that the greater proliferation of MHS cells could not be related to a higher number of growth factor receptors. Cotransport activity (bumetanide sensitive 86Rb influx in nanomoles per milligram protein per 5 minutes) was found to be significantly higher in MHS cells (16 +/- 3, n = 18) than MNS cells (8 +/- 3, n = 15) at confluence as well as in the log phase of serum-stimulated growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206587 TI - Role of brain ouabainlike compound in central nervous system-mediated natriuresis in rats. AB - Intracerebroventricular infusion of artificial sodium-rich cerebrospinal fluid induces increases in blood pressure and urinary sodium excretion. To examine the role of brain ouabainlike compound in these central nervous system-mediated responses, we evaluated the effects of prior intracerebroventricular injection of the Fab fragments of digoxin-specific antibody (Digibind, 10 mg/mL, 10 microL) on changes in blood pressure and urinary sodium excretion after intracerebroventricular infusion of high-sodium (323 mmol/L, 150 microL/kg per 15 minutes) cerebrospinal fluid in anesthetized rats. Antiouabain action of Digibind was revealed by the inhibition of a contractile response to ouabain in guinea pig aorta. Similar significant increases in blood pressure were found in rats that received preinjection of Digibind (n = 14) compared with control rats that received injection of saline (n = 5) or normal sheep IgG (n = 8). In rats pretreated with Digibind the natriuretic responses to central high sodium were significantly diminished by 68% (P < .05) or 82% (P < .05) compared with rats treated with saline or normal IgG, respectively. In contrast, Digibind did not affect either pressor or natriuretic responses to intracerebroventricular angiotensin II (600 ng/30 microL per 10 minutes). These data indicate that Digibind significantly inhibits increases in renal sodium excretion in response to high central sodium and suggest that brain ouabainlike compound may be involved in central nervous system-mediated natriuresis with nonpressor mechanisms. PMID- 8206588 TI - Epidermal growth factor-enhanced human angiotensin II type 1 receptor. AB - The human angiotensin II type 1 (AT1) receptor gene was isolated and its promoter function analyzed by deletion mutant promoter/luciferase constructs in transfected Cos 7 cells. We found that epidermal growth factor enhanced the human AT1 promoter activity twofold to threefold. The region between -227 and -366 bp from the 5' end of the cDNA was mapped for a base sequence responsive to the epidermal growth factor stimulation. By computer analysis, PEA3 transcription factor was located in this region and was shown to bind to the promoter by gel shift assay in Cos 7 and HepG2 cells. These results indicated that the human AT1 receptor enhanced by epidermal growth factor may be due to PEA3 binding to the human AT1 promoter. PMID- 8206589 TI - Dietary magnesium prevents fructose-induced insulin insensitivity in rats. AB - Increased dietary fructose may produce insulin insensitivity and elevate blood pressure in rats. It is possible that the reduced magnesium content of the high fructose commercial diet used in some studies may play a role in these abnormalities because it is known that magnesium deficiency can produce insulin insensitivity and increased angiotensin II action in humans. To study this, we maintained rats for 9 weeks on either a normal control diet, a standard high fructose diet, or the same high-fructose diet supplemented with magnesium. Glucose uptake was assessed using a perfused rat hindquarter preparation sequentially with 0, 900, and 120,000 pmol/L of added insulin. Basal serum glucose, plasma insulin, and basal glucose uptake in the absence of insulin were similar among all three groups. However, insulin sensitivity, defined as glucose uptake in the presence of 900 pmol/L insulin minus basal, was depressed in the high-fructose compared with the control group (1.02 +/- 0.38 to 1.77 +/- 0.57 mumol/g per hour, P < .05). In contrast, the high-fructose group supplemented with normal magnesium had similar insulin sensitivity as the control group (2.09 +/- 0.69 mumol/g per hour). Total serum magnesium was reduced in the high fructose group compared with control or high-fructose plus magnesium-supplemented groups. Blood pressure and fasting insulin levels were also lower in the magnesium-supplemented group. These results suggest that magnesium deficiency and not fructose ingestion per se leads to insulin insensitivity in skeletal muscle and changes in blood pressure. PMID- 8206590 TI - Blockade of distal nephron sodium transport attenuates pressure natriuresis in dogs. AB - The sodium excretory responses (UNaV) to acute changes in renal arterial pressure (RAP) during blockade of distal nephron sodium transport were evaluated in seven sodium-replete anesthetized dogs. The major distal sodium entry pathways were blocked by intrarenal infusion of amiloride (AM, 10(-5) mol/L) and bendroflumethiazide (BZ, 10(-6) mol/L). Infusion of AM plus BZ caused slight increases in renal blood flow (RBF, 4.1 +/- 0.5 to 4.6 +/- 0.4 mL.min-1.g-1; P < .001) but no changes in glomerular filtration rate (GFR, 0.96 +/- 0.05 to 1.01 +/ 0.07 mL.min-1.g-1; P = NS) or autoregulatory efficiency of RBF and GFR. There were significant increases in UNaV (2.7 +/- 0.7 to 5.2 +/- 0.6 mumol.min-1.g-1) and fractional excretion of sodium (FENa, 1.8 +/- 0.4% to 3.5 +/- 0.3%) and decreases in potassium excretion (0.59 +/- 0.10 to 0.35 +/- 0.06 mumol.min-1.g-1) during AM plus BZ infusion. During the control period and during repeat measurements in time control studies, decreases in RAP (150 to 100 mm Hg) elicited the usual decreases in UNaV (slope, 0.022 +/- 0.007 mumol.min-1.g-1.mm Hg-1; P < .01). After administration of AM plus BZ, there was a marked attenuation of the pressure-natriuretic responses, and the slopes of the RAP versus UNaV and RAP versus FENa relations at RAP levels above 100 mm Hg were not significantly different from zero. However, the pressure-natriuresis response was maintained at arterial pressure between 75 and 100 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206591 TI - Effect of administration of insulin on streptozotocin-induced diabetic hypertension in rat. AB - We have reported that streptozotocin-induced insulin-dependent diabetes mellitus in 25% reduced renal mass rats is associated with low-renin, volume-expanded hypertension and that the development of the hypertension can be prevented with insulin. In this study we examined the effect of insulin after the animals had developed sustained hypertension. Normotensive 25% reduced renal mass rats were treated with streptozotocin and, as expected, developed insulin-dependent diabetes mellitus and hypertension. After 4 weeks of sustained hypertension, neutral protamine Hagedorn insulin (6 to 8 IU/d) was administered subcutaneously for 4 weeks. As expected, insulin treatment decreased plasma glucose and increased body weight gain relative to untreated diabetic rats. On the other hand, insulin treatment did not reverse the hypertension and albuminuria. It also did not normalize extracellular fluid volume and plasma renin activity. Furthermore, insulin treatment did not reverse the increase in plasma Na+,K(+) ATPase inhibitory activity (determined by both radioimmunoassay and bioassay) and the inhibition of myocardial microsomal Na+,K(+)-ATPase activity observed in the untreated diabetic hypertensive rats. 5'-Nucleotidase, a membrane marker, was not different between insulin-treated and untreated diabetic rats. These results show that insulin, given as here described, does not reverse the insulin-dependent diabetes mellitus hypertension in 25% reduced renal mass rats once it is established, perhaps because it does not reverse the albuminuria, volume expansion, increase in endogenous digitalis-like substance, and inhibition of cardiovascular muscle cell Na+,K(+)-ATPase activity. PMID- 8206592 TI - Nitrendipine improves glucose tolerance and deoxyglucose uptake in hypertensive rats. AB - We assessed the effect of the vasodilating calcium channel blocker nitrendipine on glucose tolerance in young spontaneously hypertensive rats (SHR) (n = 15). The nitrendipine group received 1 g/kg chow for 3 weeks. Untreated SHR (n = 14) served as controls. At 3 weeks body weight was comparable, whereas systolic blood pressure was 157 +/- 9 mm Hg in nitrendipine-treated rats versus 191 +/- 10 mm Hg in controls (mean +/- SD, P < .00001). Fasting glucose was 6.8 +/- 2.7 mmol/L in nitrendipine-treated versus 8.9 +/- 1.5 mmol/L in control rats (P < .03). An intravenous glucose tolerance test (300 mg/kg) showed plasma glucose levels at 2, 5, 15, and 30 minutes to be significantly lower in the nitrendipine-treated group versus controls (two-way ANOVA, P < .03). Glucose utilization was estimated by the uptake of [3H]deoxyglucose after its intravenous administration (2 microCi/100 g body wt) to instrumented awake animals. Heart and striated muscle uptake was, respectively, 7983 +/- 5812 and 951 +/- 731 cpm.microL/g.min in the nitrendipine-treated group versus 3532 +/- 2316 and 424 +/- 201 cpm.microL/g.min in controls (P < .02 and P < .04, respectively). [3H]Deoxyglucose plasma half life and fasting and post-glucose load insulin levels were comparable in the two groups. The results show that nitrendipine improves glucose tolerance by increasing muscle glucose uptake. We suggest that glucose tolerance in SHR is influenced by muscle blood flow and can be improved by vasodilation. PMID- 8206593 TI - Insulin blunts the natriuretic action of atrial natriuretic peptide in hypertension. AB - Hyperinsulinemia and insulin resistance are implicated in the etiology of hypertension, but the mechanisms involved have not been established. The objectives of this study were to determine whether untreated essential hypertensive patients are more sensitive to the antinatriuretic action of insulin and more resistant to the counteracting natriuretic effect of atrial natriuretic peptide in contrast to age- and sex-matched normotensive control subjects. Urinary sodium excretion was measured at baseline, during hyperinsulinemic euglycemic clamp, and during coadministration of insulin and atrial natriuretic peptide. Baseline urinary sodium excretion was not significantly different in the normotensive subjects (415 +/- 47 mumol/min, n = 12) and hypertensive patients (381 +/- 18 mumol/min, n = 10); with the institution of insulin infusion, there was a similar and significant decline from baseline (P < .001) to 289 +/- 35 mumol/min in normotensive subjects and 235 +/- 17 mumol/min in hypertensive patients. Atrial natriuretic peptide was able to oppose the antinatriuretic action of insulin in normotensive subjects, increasing urinary sodium excretion significantly to a mean level of 352 +/- 31 mumol/min (P < .05), which did not differ significantly from baseline. In the hypertensive group, atrial natriuretic peptide infusion had no effect on urinary sodium excretion (238 +/- 18 mumol/min), and the difference from baseline remained highly significant (P < .001). The hypertensive patients were significantly less insulin sensitive than their normotensive counterparts, as reflected by a lower glucose utilization rate and higher mean baseline plasma insulin level (P < .05 for each).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206595 TI - Renal sensory receptor activation by calcitonin gene-related peptide. AB - In anesthetized rats we examined whether calcitonin gene-related peptide activated renal pelvic sensory receptors and, if so, whether activation of renal pelvic calcitonin gene-related peptide receptors contributes to the inhibitory renorenal reflex response to renal mechanoreceptor stimulation. Calcitonin gene related peptide (0.0026, 0.026, 0.26, and 2.6 mumol/L) administered into the renal pelvis increased ipsilateral afferent renal nerve activity in a concentration-dependent fashion (32 +/- 14%, 69 +/- 19%, 93 +/- 26%, and 253 +/- 48% [all P < .01], respectively). The increases in ipsilateral afferent renal nerve activity elicited by calcitonin gene-related peptide were associated with increases in contralateral urinary sodium excretion. The calcitonin gene-related peptide receptor antagonist human CGRP (h-CGRP) (8-37) (0.01, 0.1, 1.0, and 10 mumol/L) decreased the ipsilateral afferent renal nerve activity response to renal pelvic administration of calcitonin gene-related peptide (0.26 mumol/L) in a concentration-dependent fashion (29 +/- 4%, 33 +/- 12%, 76 +/- 9% [P < .01], and 86 +/- 13% [P < .01], respectively). In the presence of renal pelvic perfusion with vehicle, an increase in ureteral pressure of 5, 10, and 20 mm Hg increased ipsilateral afferent renal nerve activity by 13 +/- 7%, 41 +/- 7% (P < .01), and 95 +/- 15% (P < .01) and contralateral urinary sodium excretion by 8 +/ 1%, 24 +/- 4%, and 42 +/- 7% (all P < .05). The ipsilateral afferent renal nerve activity and contralateral natriuretic responses to graded increases in ureteral pressure (5 to 20 mm Hg) were unaltered by renal pelvic perfusion with h-CGRP (8 37) at 1.0 and 10 mumol/L.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206594 TI - Anteroventral third ventricle lesions abolish lumbar sympathetic responses to insulin. AB - Insulin has been shown to increase sympathetic nerve activity. Because evidence shows that insulin acts within the central nervous system, we hypothesized that lesions of the anteroventral third ventricle region, an area rich in insulin receptors, would abolish sympathetic responses to hyperinsulinemia. We measured mean arterial pressure and lumbar sympathetic nerve activity in fasted, anesthetized sham-lesioned (n = 8) and lesioned (n = 8) rats before and after intravenous insulin infusion at 0.13 U/h during euglycemic clamp. Additional sham lesioned (n = 10) and lesioned (n = 5) rats received vehicle infusion. Insulin infused sham-lesioned rats had substantially greater increases in lumbar sympathetic nerve activity (+83 +/- 18%) than vehicle-infused sham-lesioned rats (+27 +/- 4%). Most importantly, insulin-infused lesioned rats had increases in sympathetic activity (+32 +/- 11%) that were no greater than lesioned rats receiving vehicle (+23 +/- 16%). Blood pressure was not altered by insulin or vehicle. To test the possibility that lesions of the anteroventral third ventricle region nonspecifically suppress sympathetic excitatory responses, we evaluated reflex increases in lumbar sympathetic activity to nitroglycerin in sham-lesioned (n = 5) and lesioned (n = 8) rats. Rats with lesions and sham lesions showed comparable increases in lumbar nerve activity during nitroglycerin induced hypotension. In summary, increases in sympathetic nerve activity to intravenous insulin infusion are abolished by anteroventral third ventricle lesions. These data indicate that the integrity of this brain region is necessary for activation of lumbar sympathetic nerve activity by systemic administration of insulin. PMID- 8206596 TI - Rat renal interstitial bradykinin, prostaglandin E2, and cyclic guanosine 3',5' monophosphate. Effects of altered sodium intake. AB - Kinins generated intrarenally probably affect renal function by altering levels of various mediators and messengers, including prostaglandin E2 (PGE2) and cyclic guanosine 3',5'-monophosphate (cGMP). Using a microdialysis technique, we monitored levels of cortical and medullary renal interstitial fluid kinins, PGE2, and cGMP after 5 days of 0.15% (low), 0.28% (normal), or 4.0% (high) sodium intake. Samples were collected from anesthetized rats (n = 5 for each diet). During normal sodium intake, renal interstitial fluid kinin, PGE2, and cGMP levels in dialysate leaving the cortex were 113 +/- 8 pg/min, 1.23 +/- 0.11 pg/min, and 0.05 +/- 0.004 pmol/min, respectively. In the fluid leaving the medulla, the levels were 93.0 +/- 17 pg/min, 2.28 +/- 0.14 pg/min, and 0.08 +/- 0.005 pmol/min, respectively. In rats consuming a low sodium diet, renal cortical interstitial fluid kinin and cortical and medullary PGE2 and cGMP appearance rates were significantly increased (P < .01). Rats consuming a high sodium diet showed renal cortical and medullary kinin levels that were decreased 100-fold (P < .01), whereas PGE2 and cGMP were increased (P < .01) compared with levels in rats with normal sodium intake. Renal interstitial fluid kinin is extremely sensitive to dietary sodium, but changes in interstitial fluid PGE2 and cGMP are not always directionally similar, suggesting different regulations of these substances in response to sodium intake. PMID- 8206597 TI - Evidence against a role of insulin in hypertension in spontaneously hypertensive rats. CS-045 does not lower blood pressure despite improvement of insulin resistance. AB - Hyperinsulinemia resulting from peripheral insulin resistance has been demonstrated both in spontaneously hypertensive rats (SHR) and in humans with essential hypertension. A new class of antidiabetic drugs, thiazolidinediones, which can improve insulin resistance, may be able to lower not only blood glucose levels but also blood pressure. The present study was therefore designed to clarify the proportion of SHR that are glucose intolerant and to observe the effect on blood pressure of CS-045 (troglitazone) administered at 70 mg/kg per day for 2 weeks to male SHR (n = 13). Among 67 male 8-week-old SHR, 74.6% were glucose intolerant and hyperinsulinemic. Systolic blood pressure did not correlate with plasma glucose or insulin levels before or after glucose loading. Treatment with CS-045 improved insulin resistance, as evidenced by a smaller area under the curve of plasma glucose and insulin levels in response to glucose loading. However, systolic blood pressure was not altered. When the data were reanalyzed according to the presence or absence of glucose intolerance before the treatment, blood pressure in the treated group was the same as in controls despite significant improvement in steady-state plasma glucose levels. These results suggest that hyperinsulinemia and/or insulin resistance may not be involved in the development or maintenance of hypertension in SHR, which is in contrast to models of hypertension such as obese Zucker rats or fructose-fed rats. PMID- 8206598 TI - Decreased sensitivity to renal interstitial hydrostatic pressure in Dahl salt sensitive rats. AB - The ability of Dahl salt-sensitive (DS) rats to excrete a sodium load is significantly lower than Dahl salt-resistant (DR) rats. Because renal interstitial hydrostatic pressure (RIHP) is a major mediator of natriuresis in response to a sodium load, we proposed that the renal tubules of DS rats are less responsive to increases in RIHP than those of DR rats. To test this hypothesis, we determined the effect of direct increases in RIHP on renal excretory function in prehypertensive DS and DR rats. RIHP was directly increased by renal interstitial volume expansion via injection of 50 microL of a 2% albumin and saline solution into the renal interstitium through a chronically implanted renal interstitial catheter. RIHP, mean arterial pressure, glomerular filtration rate, urine flow rate, urinary sodium excretion, and fractional excretions of sodium, potassium, and lithium (an indicator of proximal tubule sodium handling) were measured before and after direct increases in RIHP in DS (n = 8) and DR (n = 8) rats. Baseline urine flow rate; urinary sodium excretion; fractional excretions of sodium, potassium, and lithium; RIHP; mean arterial pressure; and glomerular filtration rate were not different between DS and DR rats. Renal interstitial volume expansion in DS rats significantly increased RIHP (delta 4.7 +/- 0.8 mm Hg), urine flow rate (delta 14.5 +/- 3.4 microL/min), urinary sodium excretion (delta 2.62 +/- 0.62 mumol/min), and fractional excretions of sodium (delta 1.54 +/- 0.37%), potassium (delta 17.84 +/- 2.90%), and lithium (delta 19.68 +/- 3.52%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206599 TI - Increased barium influx and potassium current in stroke-prone spontaneously hypertensive rats. AB - Arterial potassium permeability is increased in hypertension. In this study we conducted voltage-clamp experiments to determine whether the whole-cell K+ current is increased in a Ca(2+)-dependent manner in aortic smooth muscle cells from stroke-prone spontaneously hypertensive rats (SHRSP). Aortic cells from Wistar-Kyoto (WKY) rats and SHRSP demonstrated an outward rectifying current elicited by depolarization. The current was carried primarily by K+, because intracellular Cs+ replacement eliminated more than 97% of the current. The current density was higher (P < .05) in SHRSP cells at positive potentials. In the presence of LaCl3 (200 mumol/L) or tetraethylammonium (10 mmol/L), the residual current was similar in WKY and SHRSP cells. Also, the current density did not differ between WKY and SHRSP cells in which the intracellular Ca2+ concentration was clamped at zero. Fura 2 ratio measurement showed similar resting myoplasmic Ca2+ concentration (Ca2+m) in WKY and SHRSP cells (100 +/- 10 versus 117 +/- 9 nmol/L, P = .2). Under low extracellular Na+ conditions, which had a minimal effect on Ca2+m, Ba2+ replacement of Ca2+ caused a continuous and approximately linear increase in the fura 2 ratio, which was twofold faster in SHRSP cells. Because Ca2+ pumps do not transport Ba2+ and Na(+)-Ca2+ exchange was inhibited by low extracellular Na+, this increase reflected unidirectional Ba2+ influx.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206600 TI - Transduction mechanisms involved in the regulation of myogenic activity. AB - Vascular smooth muscle has the ability to exist in a state of maintained partial constriction. This state of partial activation is initiated and/or maintained by the mechanical effects of distending pressure acting on the vascular wall. The intrinsic ability of vascular smooth muscle to respond to these mechanical forces is referred to as the myogenic mechanism. Within the past decade the signaling mechanisms responsible for mechanotransduction of myogenic phenomena have been the focus of extensive research. Two areas of active investigation include (1) the modulation of membrane ionic conductances by pressure/stretch and (2) the pressure/stretch-induced generation of second messengers known to be involved in vascular smooth muscle contraction. This review summarizes recent work aimed at understanding the mechanotransduction process in vascular smooth muscle. PMID- 8206601 TI - Energetics of crossbridge phosphorylation and contraction in vascular smooth muscle. AB - Ca(2+)-dependent crossbridge phosphorylation is the primary mechanism governing crossbridge cycling in smooth muscle. A four-state crossbridge model in which phosphorylation is the only proposed regulatory mechanism was successful in predicting the mechanical properties of the swine carotid media including latch (sustained force with reduced crossbridge cycling). This model also predicts that the ATP consumption of crossbridge phosphorylation is approximately equal to that of crossbridge cycling and that ATP consumption will rise hyperbolically with increases in steady-state force. This review shows these predictions to be consistent with the available energetics data for the carotid media. The absolute energetic cost of covalent regulation is modest and less than the energy savings associated with latch. However, covalent regulation should reduce the total mechanical efficiency of smooth muscle relative to striated muscle. PMID- 8206602 TI - Cell-to-cell communication coordinates blood flow control. AB - The control of tissue blood flow is a dynamic process exemplified by the interaction among physical, chemical, and electrical events occurring within the vessel wall and between the vasculature and tissue parenchyma. The range of blood flow control achieved in vivo is illustrated by functional hyperemia in exercising skeletal muscle: maximal flow can exceed resting values by more than 50-fold. Blood flow control is integrated among many vessel segments, beginning with resistance arteries external to the muscle and encompassing the arteriolar network within the muscle. As metabolic demand increases, the locus of blood flow control shifts from distal arterioles, which control capillary perfusion and blood flow distribution within the tissue, to the proximal arterioles and resistance arteries, which control the total volume of flow into the muscle. A fundamental question centers on how this vasomotor activity is actually coordinated throughout the resistance network. The interaction within and among vascular segments can be explained by chemical and electrical signals to smooth muscle cells (SMCs) and endothelial cells (ECs) in response to changes in transmural pressure as well as luminal shear stress. Increasing pressure results in SMC contraction via the myogenic response. Increasing flow stimulates ECs to release autacoids (eg, nitric oxide), which relax SMCs. Pressure and flow thereby provide opposing mechanical stimuli that interact in the maintenance of vasomotor tone throughout the resistance network. Vasomotor signals are also conducted along arterioles through cell-to-cell coupling between ECs and SMCs, thereby coordinating vasomotor activity of cells within a branch and among branches.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206603 TI - New perspectives in hypertension research. Potentials of vascular biology. AB - The vessel wall was once considered to be a passive conduit responding to the circulating endocrine system. However, the emergence of molecular and vascular biology in hypertension research has redefined our understanding of the role of the vasculature as a vital organ in the pathogenesis of hypertension. It is now recognized that the vasculature can regulate its own tone by a variety of previously unknown autocrine and/or paracrine vasoactive systems. Recent evidence indicates that the process of vascular remodeling in hypertension appears to be mediated by locally generated factors within the vessel wall. This review examines the implications of this new paradigm in hypertension, focusing on five topics that have developed through the emergence of molecular vascular biology: the discovery and characterization of novel biologically active molecules synthesized by the vessel wall, the molecular mechanisms and consequences of vascular remodeling, the developmental biology of the blood vessel and the relation to pathobiology, the use of in vivo gene transfer to test hypotheses in vivo, and novel treatment strategies based on gene therapy of the vessel wall. PMID- 8206605 TI - CIBA award for hypertension research. 1993. PMID- 8206604 TI - Pleiotropic regulation of vascular smooth muscle tone by cyclic GMP-dependent protein kinase. AB - Cyclic GMP (cGMP) mediates vascular smooth muscle relaxation in response to nitric oxide and atrial natriuretic peptides. One mechanism by which cGMP decreases vascular tone is by lowering cytosolic Ca2+ levels in smooth muscle cells. Although mechanisms by which cGMP regulates cytosolic Ca2+ are unclear, an important role for the cGMP-dependent dependent protein kinase in regulating Ca2+ has been proposed. Cyclic GMP-dependent protein kinase has been shown to regulate several pathways that control cytosolic Ca2+ levels: inositol 1,4,5-trisphosphate production and action, Ca(2+)-ATPase ATPase activation, and activation of Ca(2+) activated K+ channels. The pleiotropic action of cGMP-dependent protein kinase is proposed to occur through the phosphorylation of important proteins that control several signaling pathways in smooth muscle cells. One potential target for cGMP dependent protein kinase is the class of okadaic acid-sensitive protein phosphatases that appears to regulate K+ channels among other potentially important events to reduce cytosolic Ca2+ and tone. In addition, cytoskeletal proteins are targets for cGMP-dependent protein phosphorylation, and it is now appreciated that the cytoskeleton may play a key role in signal transduction. PMID- 8206606 TI - Fourth Bristol-Myers Squibb Lifetime Achievement Award in Hypertension. 1993. PMID- 8206607 TI - Tenth Annual Marion Merrell Dow Hypertension Research Clinical Fellowship Award. 1993. PMID- 8206608 TI - Harry Goldblatt Award in Cardiovascular Research. 1993. PMID- 8206609 TI - Corcoran Lecture. Angiotensin-converting enzyme inhibition and the heart. PMID- 8206610 TI - Changes in renal angiotensin II receptors in spontaneously hypertensive rats by early treatment with the angiotensin-converting enzyme inhibitor captopril. AB - We tested the hypothesis that in utero treatment with the angiotensin-converting enzyme inhibitor captopril could change the affinity, density, and/or subtypes of angiotensin II (Ang II) receptors in the kidneys of spontaneously hypertensive rats (SHR). Newborn, 7-day-old, and 4-month-old SHR and Wistar-Kyoto (WKY) rats were used. SHR and WKY rat breeders were treated with captopril (0.4 mg/mL, 100 mg/kg per day) in drinking water, and their pups were maintained on captopril treatment until experimentation. Control groups were untreated, age-matched SHR and WKY rats. The density, affinity, and subtypes of renal Ang II receptors were determined using radioligand binding techniques and receptor antagonists specific for Ang II receptor subtypes 1 and 2 (losartan, an AT1-specific antagonist, and CGP 42112B, an AT2-specific antagonist). AT1 receptor density in kidneys was higher than AT2 receptor density in both neonatal and adult rats. AT1 receptor density in kidneys increased approximately twofold from birth to 7 days of age in all groups. Newborn and 7-day-old SHR showed significantly greater Ang II receptor densities in kidneys than other rat groups because of significantly greater densities of both AT1 and AT2 receptors. At 4 months of age, there were no significant differences in Ang II receptor densities in kidneys between captopril-treated and control SHR. Our data indicate that the expression of AT1 and AT2 receptors in kidneys is differentially regulated during development. Enhanced activity of the renal renin-Ang II system in newborn and probably fetal SHR may be involved in the pathogenesis of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206611 TI - Angiotensin II alters aortic fibronectin independently of hypertension. AB - We performed these studies to assess the potential role of hemodynamic forces in mediating the changes in aortic fibronectin mRNA expression that occur in the rat in response to angiotensin II administration. With the use of an acute hypertensive model involving a 3-day infusion with a pressor dose of angiotensin II given by osmotic minipump, a selective increase in fibronectin mRNA expression but not of several other extracellular matrix genes was documented. This change was inhibited by losartan, indicating the importance of angiotensin receptors in the response. Prazosin, hydralazine, or L-arginine added to the drinking water all lowered the angiotensin II-induced increase in blood pressure but did not attenuate the increase in fibronectin mRNA expression. Angiotensin-converting enzyme inhibition using trandolapril did reduce fibronectin mRNA in the angiotensin II-infusion model, despite an inability to reduce blood pressure, whereas when angiotensin I was infused, quinapril lowered both blood pressure and fibronectin expression even at doses that did not completely normalize blood pressure. These studies suggest that angiotensin II induced an increase in aortic fibronectin mRNA that was not dependent solely on blood pressure. PMID- 8206612 TI - Losartan inhibits sympathetic and cardiovascular responses to carotid occlusion. AB - We have reported that inhibition of angiotensin-converting enzyme with captopril attenuates the cardiovascular responses to bilateral carotid occlusion in conscious rabbits and proposed that the attenuation results from removal of a facilitatory action of angiotensin II on the sympathetic nervous system. The aim of the present study was to assess the effect of carotid occlusion on renal sympathetic nerve activity in conscious rabbits and to investigate the effect of the angiotensin II subtype 1 (AT1) receptor antagonist losartan on the cardiovascular and renal sympathetic nerve activity responses to carotid occlusion. In seven conscious, aortic depressor nerve-sectioned rabbits, carotid occlusion elicited prompt and reproducible increases in mean arterial pressure from 75 +/- 2 to 124 +/- 5 mm Hg (P < .001), heart rate from 285 +/- 8 to 317 +/- 9 beats per minute (P < .01), and renal sympathetic nerve activity to 165 +/- 11% of control (P < .01). In the same rabbits, losartan (5 mg/kg i.v.) decreased mean arterial pressure by 9 +/- 2 mm Hg (P < .01), increased renal sympathetic nerve activity to 143 +/- 13% of control (P < .05), but did not alter heart rate. Losartan significantly attenuated (P < .01) the mean arterial pressure (66 +/- 2 to 81 +/- 2 mm Hg), heart rate (282 +/- 9 to 289 +/- 7 beats per minute), and renal sympathetic nerve activity (143 +/- 13% to 159 +/- 15% of control) responses to carotid occlusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206613 TI - Vasomotor responses in cyclosporin A-treated rats after chronic angiotensin blockade. AB - Chronic angiotensin-converting enzyme (ACE) inhibition prevents endothelial dysfunction in hypertension and hypercholesterolemia. Long-term treatment with cyclosporin A impairs endothelium-dependent relaxations and augments contractions to angiotensin II in the rat aorta. The present study compares vasomotor responses to several vasoconstrictor and dilator stimuli after 6 weeks of oral treatment with either the angiotensin-converting enzyme inhibitor lisinopril (10 mg/kg per day), the angiotensin subtype 1 receptor antagonist D 8731 (10 mg/kg per day), cyclosporin A (15 mg/kg per day), or a combination of cyclosporin A with lisinopril or D 8731 (n = 15 rats per group). Twenty-four hours after the last treatment, aortic rings were mounted in organ chambers for measurement of isometric force. Endothelium-dependent relaxations to acetylcholine and calcium ionophore were impaired by cyclosporin A but not affected by the vasodilators. Cyclosporin A-induced endothelial dysfunction was prevented by cotreatment with lisinopril or D 8731. Relaxations to nitroglycerin, SIN-1, and forskolin were not affected by any treatment. Contractions to phenylephrine and serotonin were reduced by lisinopril but not by D 8731. In contrast, contractions to angiotensin II were augmented by cyclosporin A, lisinopril, and the combination of both but not by D 8731 or D 8731 plus cyclosporin A. The data suggest a role for angiotensin II in cyclosporin A-induced endothelial dysfunction. Chronic ACE inhibition reduces overall smooth muscle contractility. The selective augmentation of angiotensin II effects by ACE inhibition and cyclosporin A suggests upregulation of angiotensin receptors in the aortic smooth muscle by these treatments. Chronic angiotensin subtype 1 receptor blockade does not appear to affect angiotensin receptor function. PMID- 8206614 TI - In vivo occupancy of angiotensin II subtype 1 receptors in rat renal medullary interstitial cells. AB - Angiotensin II receptor binding sites in type 1 interstitial cells in the inner stripe of the outer medulla are readily labeled in vitro by the radioligand but not in vivo after systemic radioligand administration. In anesthetized rats, we investigated if reduced vascular delivery due to angiotensin II-induced renal vasoconstriction or, alternatively, prior occupancy of these sites by endogenous angiotensins modulates angiotensin II subtype 1 receptor binding to renal medullary interstitial cells in vivo using electron microscopic autoradiography. Using 125I-angiotensin II, administered systemically, as a radioligand, binding in control rats occurred predominantly in the glomeruli and proximal tubules, while only low binding was observed in the inner stripe of the outer medulla. Pretreatment of rats with unlabeled [Sar1,Ile8]angiotensin II or with the angiotensin II subtype 1 receptor antagonist losartan before receiving the radioligand completely abolished binding to all sites. Renal vasodilatation induced by sodium nitroprusside or use of the radiolabeled antagonist analogue 125I-[Sar1,Ile8]angiotensin II did not alter binding to the inner stripe. In contrast, chronic salt loading or inhibition of angiotensin-converting enzyme by perindopril significantly increased binding not only to the cortical sites but also to the sites in the inner stripe of the outer medulla. Electron microscopic autoradiographs of the inner stripe detected binding in the interstitial cells only in rats treated with chronic salt loading or perindopril. These results suggest that endogenous angiotensins may modulate binding of circulating angiotensin II to the interstitial cells in vivo, and these angiotensin II receptor-bearing cells are more likely to be more responsive to interstitial angiotensin II than to the circulating hormone. PMID- 8206615 TI - Clonidine reverses the slowly developing hypertension produced by low doses of angiotensin II. AB - We used the centrally acting sympatholytic drug clonidine to evaluate neurogenic pressor activity in rats made hypertensive by chronic intravenous infusion of a low dose (4.0 ng.min-1) of angiotensin II (Ang II). Male Sprague-Dawley rats were instrumented with arterial and venous catheters and then housed in metabolic cages for the duration of the experiment. After 3 days of recovery from surgery, daily measurements were begun of mean arterial pressure, heart rate, water balance, and urinary electrolyte excretion. After 3 days of control measurements rats received either Ang II (4.0 ng.min-1 IV, n = 5) or saline vehicle (n = 4) continuously over a 15-day period. After the Ang II and vehicle infusions were ended, measurements were made during 3 days of recovery. On days 2, 7, and 12 of the experimental infusion period, clonidine hydrochloride was administered as a bolus (10.0 micrograms.kg-1 IA). The resulting changes in mean arterial pressure and heart rate were assessed over a 6-hour period. Fluid measurements were evaluated on a daily basis. In rats receiving only vehicle, clonidine produced no significant changes in any variable at any time. In rats given Ang II, mean arterial pressure increased from a control value (mean +/- SEM) of 106 +/- 1 mm Hg to 135 +/- 6, 139 +/- 6, and 148 +/- 4 mm Hg on days 2, 7, and 12, respectively. The antihypertensive response to clonidine after 6 hours on days 2, 7, and 12 of the Ang II infusion in these rats was -18 +/- 8, -16 +/- 5, and -23 +/- 9 mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206616 TI - Platelet-derived growth factor and angiotensin II induce different spatial distribution of protein kinase C-alpha and -beta in vascular smooth muscle cells. AB - Protein kinase C is an important second-messenger system that is translocated from the cytosol to the cell membrane on cell stimulation. We used confocal microscopy to study the spatial distribution of protein kinase C isoforms after stimulation of cultured vascular smooth muscle cells with platelet-derived growth factor and angiotensin II (Ang II). Monoclonal antibodies for the isoforms alpha and beta were used. Translocation was also assessed by Western blot. Isoform alpha was evenly distributed in the cytosol, whereas the beta isoform formed coarse granules in the perinuclear region. Both isoforms shifted from the cytosolic to the membrane fraction after exposure to Ang II (10(-7) mol/L) and platelet-derived growth factor (100 ng/mL at 6, 12, and 20 minutes). Confocal microscopy showed a rapid assembly of isoform alpha along cytosolic fibers at 6 minutes followed by a translocation toward the nucleus at 12 minutes with Ang II. Platelet-derived growth factor engendered a similar response; however, a cytoskeletal distribution was not observed. The beta isoform was rapidly translocated by both inducers to the perinuclear region and the nucleus. Our results show that inducers cause a translocation of protein kinase C isoforms not only into the cell membrane but also into the cell nucleus. We suggest that protein kinase C may also be important for nuclear signaling. PMID- 8206617 TI - Effects of angiotensin receptor subtype inhibitors on plasma angiotensin clearance. AB - The aim of this study was to determine whether angiotensin receptor subtypes play a role in angiotensin clearance from plasma. Angiotensin metabolic clearance rate was measured in rats by the constant infusion method. Increasing doses of angiotensin II were infused for 15 minutes, and blood was sampled for angiotensin II. The type 1 angiotensin II receptor antagonist losartan decreased the apparent metabolic clearance rate by > 50% at low-dose infusion, suggesting that type 1 angiotensin II receptors are involved in angiotensin II clearance from plasma. At higher angiotensin infusion rates, the-metabolic clearance rate of angiotensin was unaffected. To dissect the contribution of renin-generated angiotensin, additional experiments were performed in nephrectomized rats. In anephric rats, angiotensin clearance was unaffected by type 1 angiotensin II receptor inhibition. In contrast, the type 2 angiotensin II receptor ligand PD123319 in intact rats caused a > 50% increase in metabolic clearance rate of angiotensin at higher infusion rates (P < .05). In anephric rats, the type 2 angiotensin II receptor ligand alone or combined with type 1 receptor inhibition was without effect on the metabolic clearance rate or the T1/2 for angiotensin disappearance. These data argue against a role for type 1 or 2 angiotensin II receptors as clearance receptors. Increased clearance of angiotensin by type 2 receptor blockade in the presence but not the absence of kidneys suggests an alternative renal mechanism by which selective type 2 ligands may alter angiotensin effects. PMID- 8206618 TI - Vasoconstrictor action of angiotensin I-convertase and the synthetic substrate (Pro11,D-Ala12)-angiotensin I. AB - A chymase (also referred to as angiotensin I-convertase) specific for the conversion of angiotensin (Ang) I to Ang II has been identified in human heart. This serine protease is also present in dog and marmoset vasculature. We examined the vasoconstrictor effects of Ang II putatively generated from an angiotensin converting enzyme (ACE)-resistant convertase synthetic substrate (SUB) in vivo and in vitro. In marmosets, SUB (7 to 700 micrograms/kg i.v.) or Ang I (0.1 to 30 micrograms/kg) caused similar dose-dependent increases in mean arterial pressure (10 to 100 mm Hg) and decreases in heart rate. Pressor effects of SUB were slightly attenuated at low (but not high) doses by captopril (CAP, 1 mg/kg i.v.) and blocked by losartan (5 mg/kg i.v.); in contrast Ang I pressor effects were substantially blocked by both. In isolated canine superior mesenteric artery, Ang I-induced contraction was eliminated by losartan and reduced but not eliminated by 10 mumol/L CAP. When combined with the serine protease inhibitor chymostatin, CAP eliminated Ang I-induced contraction, but chymostatin alone had no effect. SUB-induced contraction was not blocked by CAP but was equally blocked by chymostatin (25 mumol/L) alone or by the combination of CAP (10 mumol/L) and chymostatin (25 mumol/L); losartan (10 mumol/L) eliminated SUB-induced responses. Previous studies have suggested that Ang I-convertase is important for production of Ang II in the heart. Our results are consistent with a potential role for Ang I-convertase in the production of Ang II in the vasculature, resulting in Ang II mediated vasoconstriction. PMID- 8206619 TI - Vascular renin in the guinea pig. Suppression by the renin inhibitor remikiren. AB - Angiotensin I and II are generated by the vascular wall. Whether this generation depends on renin or on other enzymes is debated. We tested the hypothesis that remikiren, a highly specific inhibitor of human and guinea pig renin, may inhibit the vascular renin-angiotensin system. Isolated hindquarters from guinea pigs were perfused with an artificial medium, and angiotensin I and II release was measured by high-performance liquid chromatography and radioimmunoassay. Guinea pig hindquarters released angiotensin I (23.8 +/- 5.6 fmol/30 min; n = 13) and angiotensin II (95.2 +/- 19 fmol/30 min; n = 13) spontaneously. Inhibition of the angiotensin I-converting enzyme by captopril (10 nmol/mL) suppressed angiotensin II by 85% and increased angiotensin I by 352% (n = 5, P < .05). Infusion of remikiren (1.6 nmol/mL) in addition to captopril decreased angiotensin I release by 68% (P < .05 versus captopril alone, n = 5 each). We conclude that renin generates angiotensin I in an isolated guinea pig resistance vessel bed. Our study demonstrates that renin rather than nonrenin enzymes is responsible for the major part of vascular angiotensin formation. PMID- 8206620 TI - Structural remodeling in hypertensive heart disease and the role of hormones. AB - In hypertension, the risk of adverse cardiovascular events, including heart failure, is increased in the presence of left ventricular hypertrophy. Morphological studies suggest that it is not the quantity but rather the quality, or structure, of myocardium that confers such risk. Iterations in tissue structure that appear in hypertensive heart disease include a remodeling of intramyocardial coronary arterioles, similar to that found in systemic organs, and a disproportionate accumulation of fibrillar collagen within their adventitia and neighboring interstitial space. Microscopic scars replacing necrotic cardiac myocytes are also evident. These expressions of fibrosis appear in the normotensive, nonhypertrophied right and hypertensive, hypertrophied left ventricles and are linked to the renin-angiotensin-aldosterone system. Cardiac myocyte growth, the major determinant of myocardial mass, is related to ventricular loading. Mechanisms responsible for the reactive and reparative fibrosis with renin-angiotensin-aldosterone system activation are under investigation. In vitro quantitative autoradiography has identified angiotensin II, aldosterone, endothelin, and bradykinin receptors in the myocardium. A nonendothelial tissue angiotensin-converting enzyme, whose binding density is marked in the matrix of heart valves, adventitia, and sites of fibrosis, irrespective of its pathogenic basis, has also been found. This angiotensin converting enzyme may be responsible for regulating local concentrations of angiotensin II and bradykinin that govern fibroblast collagen turnover. Based on a paradigm of discordant reciprocal regulation, in which a relative abundance of stimulators (eg, angiotensin II, aldosterone, and endothelins) of collagen synthesis exceeds inhibitors (eg, bradykinin, prostaglandins, and glucocorticoids), fibrous tissue appears.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206621 TI - Carotid artery distensibility and distending pressure in hypertensive humans. AB - Whether the decrease in large-artery distensibility observed in hypertensive patients is due primarily to an increase in distending pressure or to hypertension-induced changes in structural properties has been much debated. We determined noninvasively the diameter-pressure curve of the common carotid artery over the systolic-diastolic range by continuously recording both the pulsatile changes in internal diameter (high-resolution echo-tracking system) and, simultaneously on the contralateral artery, the pressure waveform (high-fidelity applanation tonometry). We then derived the distensibility/pressure curve and compared arterial distensibility in 14 normotensive subjects and 15 age- and sex matched hypertensive subjects at their respective mean arterial pressures (MAP) and at a common distending pressure: 100 mm Hg. Distensibility decreased as blood pressure increased, and distensibility at MAP was significantly lower in hypertensive than in normotensive subjects (7.8 +/- 0.7 versus 11.7 +/- 1.7 kPa 1.10(-3), mean +/- SEM; P < .05). In hypertensive subjects, the distensibility pressure curve was shifted toward higher levels of blood pressure, and a large part of the curve overlapped that of normotensive subjects. No significant downward shift of the distensibility-pressure curve was observed in hypertensive subjects, and distensibility at 100 mm Hg was not significantly different from that of normotensive subjects (10.0 +/- 1.0 versus 9.0 +/- 1.1 kPa-1.10(-3)). Distensibility at 100 mm Hg decreased with aging (P < .05) and was not reduced in hypertensive subjects compared with normotensive subjects after adjustment for age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206622 TI - Increased expression of growth hormone receptor mRNA and insulin-like growth factor-I mRNA in volume-overloaded hearts. AB - Recent results suggest that insulin-like growth factor-I (IGF-I) may be involved in the transition of a hemodynamic load into cardiac hypertrophy and that the expression of IGF-I seems to be coupled to increased wall stress. The present study investigated the role of growth hormone (GH) and IGF-I in myocardial hypertrophy induced by volume overload. An aortocaval fistula (ACF) was created in male Wistar rats, and experiments were performed 2, 4, and 7 days after the onset of volume overload. Right and left ventricular (RV and LV, respectively) myocardial expression of GH receptor mRNA and IGF-I mRNA were quantitated by a solution hybridization RNase protection assay. RV GH receptor mRNA content was elevated on the fourth and seventh days after the induction of the shunt, with peak levels (0.63 +/- 0.16 versus 0.14 +/- 0.03 amol/microgram DNA for the sham operated animals; P < .01) after 4 days. Similarly, IGF-I mRNA was significantly increased in the RV of shunted animals (1.26 +/- 0.13 versus 0.56 +/- 0.05 amol/micrograms DNA; P < .01) 7 days after surgery. In the left ventricle, where systolic pressure was reduced in ACF rats, no differences could be detected in GH receptor and IGF-I mRNA content between ACF and sham-operated rats on any of the experimental days. There was no difference in the ratio of RV to LV weight during the experimental period. We have shown that the thin-walled right ventricle responds to volume overload with an increase of GH receptor mRNA content followed by elevated expression of IGF-I mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206623 TI - Intraglomerular expression of alpha-smooth muscle actin in aging mice. AB - To determine whether chronic treatment with enalapril initiated early in life prevents glomerular injury secondary to normal aging, CF1 mice received enalapril (20 mg/L, n = 10) or nifedipine (40 mg/L, n = 10) in their drinking water from the time of weaning to 12 months of life. Control mice (n = 10) received tap water ad libitum. Immunocytochemical detection of renin confirmed that angiotensin-converting enzyme inhibition resulted in recruitment of renin containing cells along the preglomerular vessels. Morphometric analysis of glomeruli included assessment of glomerular diameter and the percentage of mesangial area per glomerulus. Glomerular diameter and mesangial area were higher in control mice (99.7 +/- 0.5 microns, 12.7 +/- 0.3%) than in enalapril-treated mice (88 +/- 0.8 microns, 8.6 +/- 0.6%) (P < .05). Glomerular diameter and mesangial area in the nifedipine-treated group (99.1 +/- 0.9 microns, 12.4 +/- 0.9%) were not different from control mice. These results demonstrate that angiotensin-converting enzyme inhibition prevents the glomerular enlargement and mesangial expansion observed during natural aging. In addition, control glomeruli expressed alpha-smooth muscle actin in a mesangial distribution. This effect was prevented by enalapril treatment but not by nifedipine. We conclude that long term treatment with enalapril from early life prevents the early changes associated with glomerular injury and expression of alpha-smooth muscle actin in the glomerulus. alpha-Smooth muscle actin may participate in and serve as an early marker of the glomerular injury during the normal aging process. PMID- 8206624 TI - A photoactivable source of relaxing factor in genetic hypertension. AB - Deendothelialized rings of rabbit aorta relax after exposure to UV light because of release of a relaxing factor that is similar if not identical to nitric oxide. We tested the hypothesis that production of the photo-induced relaxing factor is impaired in a rat model of genetic hypertension. Thoracic aortas were removed from adult Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats. The vessels were cut into rings, denuded of endothelium, and placed in a muscle bath for isometric force measurement. Rings were contracted with phenylephrine, and relaxation was measured after exposure to UV light. Aortic rings from stroke prone spontaneously hypertensive rats relaxed to a greater extent after exposure to UV light than did rings from Wistar-Kyoto rats. An inhibitor of nitric oxide synthase (N omega-nitro-L-arginine) greatly potentiated the relaxation responses to light in both strains, and these enhanced relaxations were attenuated by tetraethylammonium chloride, potassium chloride, ouabain, or inhibitors of guanylate cyclase. These results suggest that UV irradiation induces relaxation in aortic smooth muscle that is greater in hypertensive than normotensive rats and is greatly enhanced after addition of inhibitors of nitric oxide production. Thus, the unidentified photo-induced relaxing factor is not solely nitric oxide but may also represent either a hyperpolarizing factor, because depolarization blocks the responses entirely, or possibly smooth muscle guanylate cyclase that might itself be photoactivable. PMID- 8206625 TI - A kallikrein-like enzyme in the aorta of normotensive and hypertensive rats. AB - We evaluated whether vascular kallikrein is altered in rats with genetic or experimental hypertension. Group 1 was infused intraperitoneally with angiotensin II (Ang II) or vehicle for 4 weeks; group 2 was injected subcutaneously with deoxycorticosterone (75 mumol/kg once a week) or vehicle for 4 weeks; group 3 consisted of uninephrectomized rats on high sodium intake given deoxycorticosterone or vehicle; and group 4 consisted of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Active and total kallikrein activity was measured in abdominal aortic homogenates using an amidolytic assay. Ang II increased systolic blood pressure at a dose of 400 nmol/kg per day (146 +/ 6 versus 123 +/- 3 mm Hg in controls, P < .01) but not at 80 nmol/kg per day. Deoxycorticosterone did not increase blood pressure except in uninephrectomized rats on high salt (173 +/- 6 versus 135 +/- 4 mm Hg in controls, P < .01). Blood pressure averaged 194 +/- 2 mm Hg in SHR and 123 +/- 3 mm Hg in WKY rats. Vascular kallikrein was similar in rats given Ang II or vehicle. In deoxycorticosterone-treated rats total kallikrein was higher than in controls (9.2 +/- 0.8 versus 3.5 +/- 0.1 pkat/mg protein, P < .05), whereas active kallikrein did not differ (0.09 +/- 0.04 versus 0.09 +/- 0.03 pkat/mg protein, P = NS). A similar pattern was observed in uninephrectomized deoxycorticosterone treated rats (active, 0.09 +/- 0.03 versus 0.10 +/- 0.04, P = NS; total, 7.4 +/- 0.7 versus 4.1 +/- 0.2 pkat/mg protein, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206626 TI - Atrial natriuretic peptide and C-type natriuretic peptide in spontaneously hypertensive rats and their vasorelaxing actions in vitro. AB - The present study determined circulating concentrations of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) and also investigated the vasorelaxing action of ANP and CNP on isolated contracted aorta. We also defined the vasorelaxing action of a novel and newly synthesized 27-amino acid chimera of ANP and CNP termed vasonatrin peptide (VNP), which we compared with ANP and CNP in WKY rats and SHR. Plasma and urinary cyclic GMP and sodium excretion were also investigated. Plasma ANP was increased in SHR in contrast to no change in circulating CNP. Plasma and urinary cyclic GMP and sodium excretion were no different between WKY rats and SHR. In WKY rats maximal relaxations to VNP in aortic rings without endothelium were greater than those to ANP and CNP. In SHR aortic rings the potency of VNP relaxation was preserved, the actions of ANP were enhanced, and the actions of CNP were markedly impaired. In association with these vasorelaxing actions, these data suggest that (1) circulating CNP is not different in SHR and WKY rats, but the aortic relaxing action of CNP is markedly impaired in SHR; (2) endogenous plasma ANP is significantly increased in SHR without associated increases in plasma or urinary cyclic GMP; (3) there is an increase in aortic relaxation to exogenous ANP in SHR; and (4) VNP has a potent endothelium-independent aortic relaxing action in both WKY rats and SHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206627 TI - Guanine nucleotide-binding proteins in aortic smooth muscle from hypertensive rats. AB - To explore the hypothesis that altered vascular muscle signal transduction may underlie some of the vascular changes observed in hypertensive models, we measured expression of GTP-binding protein (G protein) alpha-subunits, Gs, G(i), and Gq, in aortic muscle of reduced renal mass and sham-operated rats and proximal and distal aortic segments from rats with interrenal aortic coarctation (IR-AC). G protein expression was measured by immunoblot analysis. When we probed aortic muscle membrane with G(i) and Gq alpha-subunit antibodies, we identified 41- and 42-kD immunoreactive proteins, respectively. Three immunoreactive bands specific to Gs alpha-subunit antibody were resolved. Immunoreactive blot densities were compared. In aortic muscle membrane of reduced renal mass rats (blood pressure, 148 +/- 7 mm Hg), we found significantly reduced Gs and G(i) blot densities compared with sham-operated controls (blood pressure, 99 +/- 12 mm Hg). There were no differences in Gq blot densities between reduced renal mass and control rats. Gs and G(i) blot densities were significantly lower in IR-AC proximal aortic segments (carotid pressure, 165 +/- 5 mm Hg) and distal aortic segments (femoral pressure, 121 +/- 4 mm Hg) than in aortas of sham-operated controls. In contrast, Gq expression was significantly increased in the high pressure proximal aortic segments compared with low-pressure distal aortic segments from IR-AC rats. Thus, altered G protein expression occurs in aortic muscle from nongenetic rat models of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206628 TI - A local kallikrein-kinin system is present in rat hearts. AB - It has been reported that kinins mediate part of the beneficial cardiac effects induced by treatment with angiotensin-converting enzyme inhibitors in situations such as ischemia-reperfusion injury, myocardial infarction, and cardiac hypertrophy. However, it is not known whether the heart contains an independent kallikrein-kinin system. We measured kallikrein in tissue and in the incubation medium of heart slices. Heart slices released active and total (trypsin activatable) kallikrein into the medium (46 +/- 5 and 380 +/- 18 pg bradykinin/mg, respectively, after 1 hour and 78 +/- 6 and 654 +/- 14 pg bradykinin/mg after 2 hours, n = 7). Release was not due to tissue damage because lactate dehydrogenase, a cytosolic marker, decreased from 8.9 +/- 2.9 to 2.9 +/- 1.0 U/mg per hour. Although kallikrein was released, total tissue kallikrein in the slices did not change (423 +/- 25 pg bradykinin/mg in nonincubated slices and 370 +/- 42 pg bradykinin/mg after 2 hours, P = NS), suggesting pool replenishment. Cardiac kallikrein activity was inhibited by incubation with anti glandular kallikrein antibodies. Pretreatment with the protein synthesis inhibitor puromycin (10 mg IP) lowered release of active kallikrein from 78 +/- 6 to 22 +/- 4 pg bradykinin/mg and total kallikrein from 654 +/- 14 to 113 +/- 9 pg bradykinin/mg (P < .001). By using reverse transcription polymerase chain reaction with kallikrein family oligonucleotide primers and a specific kallikrein probe, we found that mRNA for tissue kallikrein is present in both atrial and ventricular RNA. Kallikrein activity was also detected in primary cultures of neonatal rat atrial and ventricular cardiocytes and their incubation medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206629 TI - Furosemide elicits nonuniform reflex responses via cardiac sympathetic afferents. AB - To examine whether furosemide elicits a cardiorenal reflex response via stimulation of cardiac afferents, furosemide was administered intrapericardially in sinoaortic denervated rats. The role of vagal afferents was evaluated by intrapericardial (IPC) administration of furosemide before and after bilateral vagotomy. The role of cardiac sympathetic afferents was examined by IPC administration of furosemide before and after IPC lidocaine blockade in rats with bilateral vagotomy. Low-dose furosemide (10 micrograms) elicited renal sympathoinhibition, whereas high-dose furosemide (1000 micrograms) produced a rapid and transient change in efferent renal sympathetic nerve activity of either inhibitory (19/49, or 39%) or excitatory (30/49, or 61%) nature. The responses were not affected by vagotomy but were abolished by IPC lidocaine blockade. In rats with a renal sympathoinhibitory response to IPC administration of 1000 micrograms furosemide, both the hypotensive and sympathoinhibitory responses were inhibited by indomethacin, whereas indomethacin did not affect reflex responses in rats showing a renal sympathoexcitatory response to IPC injection of 1000 micrograms furosemide. We conclude that furosemide elicits a nonuniform reflex response mediated via cardiac sympathetic afferents of which the renal sympathoinhibitory response is dependent on intact cyclooxygenase function. PMID- 8206630 TI - Insulin-induced Ca2+ transport is altered in vascular smooth muscle cells of spontaneously hypertensive rats. AB - Intracellular calcium may be a mediator of insulin action in vascular smooth muscle cells. This study investigates effects of physiological concentrations of insulin on intracellular free calcium concentrations in primary unpassaged vascular smooth muscle cells derived from 3- and 17-week-old normotensive rats (Wistar and Wistar-Kyoto) and spontaneously, hypertensive rats (SHR). Underlying mechanisms responsible for insulin-evoked calcium responses were also studied. Basal calcium was significantly higher in 17-week SHR cells (134 +/- 8 nmol/L) compared with cells from Wistar-Kyoto (98 +/- 12 nmol/L) and Wistar (99 +/- 10 nmol/L) rats. Insulin (70 microU/mL) significantly increased calcium in all cells. Responses from 3-week rat cells were similar. The increase was amplified in 17-week SHR cells (177 +/- 7 nmol/L) compared with Wistar-Kyoto (130 +/- 14 nmol/L) and Wistar (132 +/- 16 nmol/L) cells. Genistein (0.1 mumol/L) and tyrphostin 23 (0.1 mumol/L) (tyrosine kinase inhibitors) completely abolished insulin-induced calcium effects. Stimulatory effects of insulin were significantly inhibited by 0.1 mumol/L diltiazem, staurosporine, calphostin C, and thapsigargin. The inhibitory effects of diltiazem (calcium channel antagonist) and the protein kinase C inhibitors staurosporine and calphostin C were significantly lower in cells from hypertensive compared with those from normotensive rats. Calcium recovery after insulin administration was delayed in SHR cells. In conclusion, insulin increases vascular smooth muscle cell calcium concentrations, possibly via calcium channel activation, protein kinase C mediated mechanisms, and intracellular calcium mobilization. Alterations of these pathways as well as impaired calcium recovery to baseline may be associated with increased insulin-sensitive calcium responses in cells from SHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206631 TI - C-type natriuretic peptide upregulates vascular endothelin type B receptors. AB - Cultured rat vascular smooth muscle cells (VSMCs) possess receptors for potent vasoconstrictor endothelin-1 (ET-1) as well as potent vasodilator natriuretic peptides (atrial, brain, and C-type natriuretic peptides [ANP, BNP, and CNP, respectively]). However, little is known about molecular interactions between endothelin receptors and natriuretic peptides in VSMCs. To elucidate whether natriuretic peptides regulate vascular endothelin receptors, we studied the effects of three natriuretic peptides on the capacity of 125I-ET-1 binding and expression of endothelin type A (ETA) and type B (ETB) receptor mRNAs in cultured rat VSMCs. CNP (10(-6) mol/L) increased 125I-ET-1 binding capacity in a time dependent manner (6 to 48 hours) and stimulated cyclic GMP (cGMP) generation in a dose-dependent manner (10(-8)) to 10(-6) mol/L). Pretreatment with CNP (10(-8) to 10(-6) mol/L) and 8-bromo-cGMP (10(-5) to 10(-3) mol/L) for 24 hours resulted in dose-dependent increases in 125I-ET-1 binding in VSMCs. The three natriuretic peptides at the highest concentration (10(-6) mol/L) increased 125I-ET-1 binding and stimulated cGMP generation with almost the same rank order of efficacy (CNP > BNP > ANP). Scatchard analysis of binding studies revealed that CNP (10(-6) mol/L) and 8-bromo-cGMP (10(-3) mol/L) increased vascular endothelin receptor number by 28% and 88%, respectively, without changing its affinity. Pretreatment with both CNP and 8-bromo-cGMP increased ET-1-stimulated inositol 1,4,5 trisphosphate formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206632 TI - Remission of high blood pressure reverses arterial potassium channel alterations. AB - Rat arterial muscle cells show an elevated Ca(2+)-dependent K+ efflux during the established phase of hypertension. This association of enhanced K+ efflux with high arterial pressure implies that changes of in vivo blood pressure can alter the level of K+ channel current in arterial membranes. We directly tested this hypothesis by comparing K+ current density between patch-clamped aortic muscle membranes of normotensive Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), and SHR treated with the angiotensin-converting enzyme inhibitor ramipril (3.5 mg/kg per day PO) to normalize blood pressure. Peak macroscopic K+ current was measured during progressive depolarizing steps (10 mV) from -60 and +60 mV in cells dialyzed with pipette solution containing 10(-6) mol/L calcium to amplify Ca(2+)-dependent K+ current. With the use of this approach, maximum K+ current density in aortic muscle membranes of untreated SHR was 2.6-fold higher than in untreated WKY rats (SHR, 31 +/- 3 pA/pF; WKY, 12 +/- 1 pA/pF) and was predominantly blocked by 2 mmol/L tetraethylammonium. K+ current density in SHR aortic membranes was unchanged after 1 week of ramipril therapy, but it was reduced 42% (to 18 +/- 1 pA/pF) after 2 weeks of treatment. Parallel tension recording studies showed that untreated SHR aortic segments but not aortic segments from WKY rats or ramipril-treated SHR constricted strongly after block of Ca(2+)-dependent K+ channels by tetraethylammonium. Our findings imply that Ca(2+)-dependent K+ current density in arterial muscle membranes shows a positive correlation with chronic arterial blood pressure levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206633 TI - Enhanced vascular reactivity to mastoparan, a G protein activator, in genetically hypertensive rats. AB - Vascular smooth muscle from stroke-prone spontaneously hypertensive rats has an increased responsiveness to the vasoconstrictors angiotensin II and serotonin. This abnormality is postulated to contribute to the hypertension characteristic of this strain of rats. We hypothesized that a portion of the increased responsiveness may be due to altered function of G proteins. This hypothesis was tested using mastoparan, a peptide that mimics ligand-bound receptors to stimulate G proteins directly. In addition, we investigated the mechanism of mastoparan-induced contraction of vascular smooth muscle. Changes in isometric tension were recorded in denuded carotid artery strips from hypertensive and normotensive (Wistar-Kyoto) rats. Vascular strips from the hypertensive rats had a significantly greater response to mastoparan at all concentrations between 10( 8) and 10(-5) mol/L. A G protein inhibitor, N-ethylmaleimide (10(-3) mol/L), attenuated the response to mastoparan (10(-7) mol/L) (67 +/- 4% of control response), whereas pertussis toxin treatment did not. Inhibition of phospholipase C also significantly decreased the mastoparan-induced response (23 +/- 12% of control), and nifedipine (10(-3) mol/L), a calcium channel blocker, completely blocked the mastoparan-induced contraction. Indomethacin treatment did not affect the mastoparan contraction even though mastoparan has been shown to stimulate phospholipase A2 in other cell types. In conclusion, we observed an increased response in carotid arteries from genetically hypertensive rats to a pharmacological intervention that appears to act via G protein-linked phospholipase C stimulation and L-type calcium channel activation, suggesting that the increased vascular reactivity in stroke-prone spontaneously hypertensive rats is due in part to altered function of G proteins. PMID- 8206634 TI - Mechanisms involved in the cardiovascular-renal actions of nitric oxide inhibition. AB - The roles of the sympathetic nervous system, angiotensin II, and arginine vasopressin in the cardiovascular-renal responses to nitric oxide synthesis inhibition were examined in eight conscious dogs equipped with arterial and venous catheters and a nonoccluding bladder catheter. Nitric oxide inhibition was achieved by intravenous infusion of NG-nitro-L-arginine methyl ester (L-NAME) at 37.1 nmol/kg per minute for 140 minutes in the control group. The same dogs, after a 1-week recovery, were pretreated for 2 days with either prazosin for alpha 1 blockade, prazosin plus propranolol for alpha 1 plus beta blockade, L 158,809 for angiotensin receptor blockade, or d(CH2)Tyr(Me)arginine vasopressin for vasopressin-V1 blockade, and the L-NAME infusion was repeated. After 140 minutes of L-NAME infusion into the control group, mean arterial pressure and renal vascular resistance had increased 16% and 71%, and renal blood flow, glomerular filtration rate, urine flow, and urinary sodium excretion had decreased 33%, 16%, 61%, and 64%, respectively. The decrement in renal blood flow and glomerular filtration during L-NAME administration was unaffected by any of the neurohumoral blockers. During V1 blockade L-NAME resulted in only a 3% increase in arterial pressure, attenuation of the renal vascular resistance response, and almost total elimination of the decrease in urine flow. During angiotensin blockade the L-NAME-induced increase in arterial pressure was markedly attenuated, and the decrease in urinary sodium excretion was attenuated in the alpha 1 plus beta blockade group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206635 TI - Cyclosporine produces endothelial dysfunction by increased production of superoxide. AB - Vasoconstriction and hypertension are major side effects of cyclosporine therapy. The mechanism or mechanisms responsible for the vascular effects of cyclosporine are unclear. The vascular effects of cyclosporine may arise as a consequence of endothelial dysfunction induced by the agent. To test this possibility, we compared in vessels prepared in myographs endothelium-mediated relaxations of mesenteric resistance arteries of Wistar-Kyoto rats treated for 21 to 28 days with subcutaneous injections of cyclosporine (25 mg/kg per day), or vehicle. Endothelium-dependent relaxations in response to acetylcholine were impaired in arteries from cyclosporine-treated rats; the concentrations of acetylcholine required to produce 50% relaxation of norepinephrine activation (pD2) were 31.6 +/- 0.1 versus 5 +/- 0.1 nmol/L in control arteries (P < .05). Nitro-L-arginine produced comparable 10-fold decreases in sensitivity to acetylcholine in arteries from both rat groups, indicating that the relaxations were mediated by endothelium-derived nitric oxide. Acetylcholine-induced relaxations in cyclosporine-treated arteries were normalized by pretreatment of the arteries with superoxide dismutase (150 IU/mL; pD2, 3.6 +/- 0.1; P < .05); superoxide dismutase had no effect on relaxations in control arteries. SQ 29,548, an inhibitor of prostaglandin H2/thromboxane A2 receptors; H-7, an inhibitor of protein kinase C; and indomethacin did not alter relaxations in response to acetylcholine in either group of arteries. Cyclosporine-treated arteries were more sensitive than control arteries to nitroprusside, an agent that induces relaxation via nitric oxide (pD2, 1.3 and 6.2 mumol/L, respectively; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206636 TI - Nitrosyl factors mediate active neurogenic hindquarter vasodilation in the conscious rat. AB - Exposure to noxious environmental stimuli such as air-jet stress (AJS) produces a pattern of hemodynamic changes referred to as the "defense reaction". In the rat these changes include a relatively modest increase in mean arterial blood pressure (MAP), tachycardia, renal and mesenteric vasoconstriction, and a marked hindquarter vasodilation. The aim of the present study was to determine whether the AJS-induced decrease in hindquarter resistance is mediated by a sympathetic neurogenic vasodilator system that uses nitric oxide (NO) and/or related nitrosyl factors. AJS produced a small, rapid increase in MAP, which quickly returned to baseline (within 5 seconds), and a substantial increase in hindquarter blood flow and decrease in hindquarter resistance, which occurred almost instantaneously (1 to 2 seconds) and were sustained for at least 30 seconds. The intravenous injection of either bretylium (5 mg/kg), which prevents impulse propagation mediated release of neurotransmitters/neuromodulators from sympathetic terminals, or NG-nitro-L-arginine methyl ester (L-NAME, 25 mumol/kg), which blocks NO synthesis, essentially abolished the AJS-induced increase in hindquarter blood flow and fall in hindquarter resistance. In contrast, the hindquarter vasodilation produced by the NO donor sodium nitroprusside (4 micrograms/kg i.v.) was markedly exaggerated in the bretylium- or L-NAME-treated rats. We also found that rat lumbar sympathetic fibers projecting to the hindquarter vasculature contain NADPH diaphorase, a marker for NO synthase in paraformaldehyde-perfused tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206637 TI - Hypertension induced by nitric oxide synthesis inhibition is renal nerve dependent. AB - Recent studies have indicated that chronic administration of N omega-nitro-L arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, produces marked hypertension. Although the mechanism of this form of hypertension is not well understood, several studies have demonstrated that sympathetic nerve activity is at least acutely elevated after L-NAME administration. To evaluate the potential role of the renal sympathetic nerves in L-NAME-induced hypertension, we compared the blood pressure response to L-NAME in four groups of Sprague-Dawley rats (n = 8 each): (1) sham-operated vehicle-treated, (2) sham operated L-NAME-treated, (3) denervated vehicle-treated, and (4) denervated L NAME-treated. After renal denervation or sham surgery, L-NAME was added to the drinking water (70 mg/100 mL) for 4 weeks, and arterial pressure was measured weekly by the tail-cuff method. L-NAME treatment caused a progressive increase in arterial pressure in sham-operated rats, rising to 154 +/- 6 mm Hg by week 4 of treatment compared with 115 +/- 2 mm Hg in the vehicle-treated sham-operated group (P < .005). In contrast, the development of hypertension was significantly delayed and attenuated in renal-denervated rats treated with L-NAME. The results of our study suggest that L-NAME-induced hypertension may be partly mediated by or is at least dependent on the integrity of the renal nerves. PMID- 8206638 TI - Relaxation of porcine coronary artery to bradykinin. Role of arachidonic acid. AB - Bradykinin-induced relaxation of precontracted, porcine coronary artery (PCA) rings is mediated by distinctly different endothelium-derived relaxing factors depending on the contractile agent used. Thus when contracted with KCl, bradykinin-induced relaxation of PCA rings is mediated solely by nitric oxide (NO), whereas when contracted with the thromboxane mimetic U46619, a small component of the relaxation is attributable to NO and a large component is attributable to a non-NO mechanism that is independent of cyclooxygenase activity. We hypothesized that the non-NO component was mediated by arachidonic acid (AA) or by a non-cyclooxygenase product of AA metabolism. Bradykinin-induced relaxations of PCA rings precontracted with U46619 in the presence of indomethacin (10 mumol/L) were moderately attenuated by the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 100 mumol/L), whereas when precontracted with KCl, L-NAME abolished the relaxations. AA produced endothelium dependent relaxations of rings precontracted with U46619 that were unaffected by L-NAME, whereas AA did not relax rings precontracted with KCl. In rings precontracted with U46619, in the presence of L-NAME and indomethacin the phospholipase inhibitors quinacrine (50 mumol/L) and 4-bromophenacyl bromide (10 mumol/L) attenuated bradykinin- but not AA-induced relaxations. Inhibitors of both lipoxygenase (BW 755c [100 mumol/L] and nafazatrom [20 mumol/L]) and cytochrome P-450 (proadifen [10 mumol/L] and clotrimazole [10 mumol/L]) pathways did not eliminate bradykinin- or AA-induced relaxations, although clotrimazole partially attenuated AA-induced relaxations. These findings suggest that bradykinin-induced relaxation of PCA rings is mediated by AA through a mechanism that is not dependent on cyclooxygenase, lipoxygenase, or cytochrome P-450 pathways. PMID- 8206639 TI - Sympathetic baroreceptor responses after chronic NG-nitro-L-arginine methyl ester treatment in conscious rats. AB - Blood pressure elevations after nitric oxide inhibition may result in part from increased sympathetic tone. In this study arterial baroreceptor reflex control of heart rate, renal sympathetic nerve activity (RSNA), and adrenal sympathetic nerve activity (ASNA) were compared in rats given normal tap water or a 3.7 nmol/L (10 mg%) solution of NG-nitro-L-arginine methyl ester (L-NAME) for 1 or 5 weeks. L-NAME raised blood pressure after 5 weeks of treatment (153 +/- 3 versus 130 +/- 3 and 124 +/- 2 mm Hg, 5 weeks versus 1 week and control). The sensitivity of arterial baroreceptor reflex control of RSNA was reduced after both 1 and 5 weeks of treatment (-5.05 +/- 0.63% and -4.46 +/- 0.2% versus -6.43 +/- 0.39% baseline activity per millimeters of mercury). Set point gain of ASNA was attenuated after 5 weeks of treatment compared with controls (-1.7 +/- 3% versus -3.3 +/- 3% baseline activity per millimeters of mercury). Maximal inhibition of ASNA was attenuated in groups treated 1 and 5 weeks (60 +/- 3% and 66 +/- 3% versus 34 +/- 4% baseline activity). The maximal increase in both RSNA and ASNA was elevated in rats treated 5 weeks (RSNA: control, 263 +/- 19%; 1 week, 224 +/- 17%; 5 weeks, 324 +/- 20%; ASNA: control, 272 +/- 29%; 1 week, 252 +/- 31%; 5 weeks, 361 +/- 28% baseline activity). The data indicate that chronic L-NAME treatment alters arterial baroreceptor reflexes in part before the onset of hypertension. PMID- 8206640 TI - Increased activity of the Mg2+/Na+ exchanger in red blood cells from essential hypertensive patients. AB - Epidemiological, clinical, and experimental evidence suggests a relation between Mg2+ metabolism and essential hypertension. The aim of the present study was the detection of abnormalities of the erythrocyte Mg2+/Na+ exchanger in essential hypertensive patients. We studied 66 untreated essential hypertensive patients and 36 normotensive control subjects. Maximal efflux rates of total Mg2+ efflux and the Na(+)-dependent and Na(+)-independent components of Mg2+ efflux were determined in Mg(2+)-loaded red blood cells. Mg2+/Na+ exchanger was calculated as the Na(+)-dependent component of the Mg2+ efflux. Mean values of Mg2+/Na+ exchanger were clearly elevated in hypertensive subjects with respect to normotensive control subjects [184.7 +/- 15.7 versus 84.4 +/- 6 mumol(L.cell.h) 1; P < .001]. This elevation was due primarily to the increased total Mg2+ efflux [324.2 +/- 21.9 versus 257.9 +/- 17.3 mumol(L.cell.h)-1; P < .05], whereas the Na(+)-independent component was not significantly different between the groups [154.5 +/- 11.8 versus 173.4 +/- 15.5 mumol(L.cell.h)-1; P = NS]. Moreover, total erythrocyte Mg2+ content was slightly reduced in hypertensive patients with respect to normotensive control subjects (1.84 +/- 0.04 versus 2.07 +/- 0.04 mmol/L.cell; P < .001). Using the 99% confidence limits of the normotensive population as the normal range, 30 (45.5%) hypertensive subjects showed values of Mg2+/Na+ exchanger higher than 160 mumol(L.cell.h)-1. The Mg2+/Na+ exchanger was inversely correlated with basal intraerythrocyte Mg2+ content (r = -.323; P = .001). From a clinical point of view, we found a positive correlation between diastolic blood pressure values and Mg2+/Na+ exchanger (r = .246; P < .05) in the sample of essential hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206641 TI - Blunted natriuretic response to a high-sodium meal in obese dogs. Role of renal nerves. AB - Although the relation between body weight and arterial pressure is well established, the mechanisms involved in the pathogenesis of obesity-related hypertension are unclear. However, recent studies suggest that abnormalities in renal function may be involved. The purpose of this study was to test the hypothesis that obese animals have a reduced ability to excrete a sodium load as a result of abnormal renal nerve function. To quantify the role of renal nerves, we examined changes in renal hemodynamics and sodium excretion in response to a high-sodium meal (200 mmol Na) in separate innervated and denervated kidneys simultaneously within the same conscious dog. Two surgically designed hemibladders with indwelling catheters were used to collect urine from innervated and denervated kidneys of the same dog. Body weight averaged 19.9 +/- 1.0 kg in the control lean dogs and 25.1 +/- 1.1 kg in the obese dogs. Arterial pressure averaged 101 +/- 4 mm Hg in the obese dogs and 90 +/- 4 mm Hg in the lean dogs. In response to the high-sodium meal in lean dogs, urinary sodium excretion increased from 20.8 +/- 4.2 to 189.7 +/- 21.2 mumol/min in the innervated kidneys and from 25.3 +/- 5.9 to 194.8 +/- 26.9 mumol/min in the denervated kidneys. In contrast, urinary sodium excretion in obese dogs increased from 9.6 +/- 1.4 to 129.9 +/- 34.3 mumol/min in the innervated kidneys and from 18.4 +/- 3.7 to 125.2 +/- 30.5 mumol/min in the denervated kidneys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206642 TI - Elevated expression of human nonpancreatic phospholipase A2 in psoriatic tissue. AB - In involved psoriatic tissue, which is characterized by chronic inflammation in both epidermis and dermis, elevated levels of arachidonic acid and eicosanoids have been measured. This implies that a phospholipase A2 (PLA2) may be involved in the pathogenesis of psoriasis. The PLA2's are a group of enzymes that release unsaturated fatty acids from the sn2-position of membrane phospholipids. Once released, the fatty acids are converted by various enzymes into biologically very important signaling molecules. Release of arachidonate initiates the arachidonate cascade, leading to the synthesis of eicosanoids such as prostaglandins, thromboxanes, leukotrienes, and lipoxines. Eicosanoids are important in a variety of physiological processes and play a central role in inflammatory mediators, such as lyso-PAF (a precursor for PAF) and other lysophospholipids, may also be formed through the action of a PLA2. We report for the first time the detection of transcripts of nonpancreatic phospholipase A2 (npPLA2, type II) and cytosolic (c) PLA2 in human skin, and overexpression of npPLA2 in involved skin from patients with psoriasis (plaque psoriasis and pustular psoriasis). Limited amounts of npPLA2 enzyme are detected immunologically in the uppermost layers of epidermis from healthy persons. Both involved and uninvolved psoriatic epidermis contain higher levels of npPLA2 than normal skin. Positive cells in dermis showed significantly higher levels of npPLA2 than epidermal cells. In dermis from healthy persons, only weak staining of a few cells could be detected. The two PLA2 enzymes detected in psoriatic skin (cytosolic and nonpancreatic) may both be involved in eicosanoid overproduction in psoriatic tissue, and the npPLA2 may also be involved in potentiating cell activation, especially T cells. PMID- 8206644 TI - Hyaluronan and myeloperoxidase in human peritoneal fluid during genital inflammation. AB - The changes in concentration of hyaluronan (HYA) and myeloperoxidase in the peritoneal fluid (PF) were studied during genital intraperitoneal inflammation. PF were collected from 111 women undergoing laparotomy for adhesiolysis and reconstructive surgery of the fallopian tubes or laparoscopy in search of causes of infertility or low abdominal pain. When the number of leukocytes in the PF had been counted, the fluid samples were centrifuged and the supernatants analyzed for the concentrations of HYA and myeloperoxidase. During genital inflammation, whether postoperative or postinfectious, leukocytosis and elevated levels of HYA and myeloperoxidase were found in the PF. Concentrations of these substances in the PF may be usable as clinical markers for genital inflammation. PMID- 8206643 TI - Doxycycline reduction of F-actin content of human neutrophils and fibroblasts. AB - We and others have shown that tetracyclines inhibit leukocyte adherence, migration, and phagocytosis, functions presumed to involve actin microfilament metabolism. In this study we investigated the influence of a tetracycline (doxycycline, Dc) on neutrophil and fibroblast actin metabolism. Human neutrophils and fibroblasts were pretreated with Dc or cytochalasin B (cB), stimulated with either the chemotactic peptide FMLP or phorbol myristate acetate (PMA), and the changes in phalloidin conjugate, associated F-actin were followed microscopically or quantified fluorometrically. Doxycycline suppressed, in a dose related manner, the rise in F-actin content of neutrophils that normally follows their activation with either FMLP or PMA. Cytochalasin B had a similar affect on actin microfilament synthesis. Incubation of fibroblasts in Dc led to a loss of actin microfilaments and caused flattened adherent cells to round up and detach. Both Dc and cB also inhibited Con A-induced acceptor capping on neutrophils, a phenomenon known to be dependent on the presence of intact actin microfilaments. The data show that both Dc and cB influence actin metabolism and suggest they do so by differing mechanisms. PMID- 8206645 TI - Expression and secretion of active mouse TIMP-1 using a baculovirus expression vector. AB - Mouse TIMP-1, one of the tissue inhibitors of metalloproteinases important in regulating turnover of extracellular matrix in both normal and pathological tissues, was previously expressed in E. coli in an inactive, nonglycosylated state that required refolding to become functional. Due to the difficulty of renaturation, an alternative to the prokaryotic expression system was sought. Since we are interested in studying the pharmacodynamics and pharmacokinetics of TIMP locally administered by controlled delivery to mice with experimentally induced arthritis, we also needed an efficient way of producing active TIMP in large quantities. Using the pBlueBacII transfer vector, we generated a recombinant baculovirus that in Sf9 cells could express glycosylated mouse TIMP-1 to about 3 mg of active protein/liter conditioned medium. PMID- 8206646 TI - Human recombinant platelet phospholipase A2 exacerbates poly-L-arginine induced rat paw edema. AB - In this study by using the human recombinant non-pancreatic-secreted platelet PLA2 (r-hnps-PLA2) and rabbit polyclonal antibodies directed against either the human (group II) or the porcine enzyme (group I), we have shown a possible involvement of platelet PLA2 in poly-L-arginine (25 kDa)-induced rat paw edema. Local treatment of rats with the anti-platelet-PLA2 antibody (anti-hnps-PLA2) but not with anti-porcine-PLA2 antibody (anti-porc-PLA2) significantly reduced the edema induced by a maximal dose of poly-L-arginine (1 mg/paw). Furthermore when r hnps-PLA2 (1-10 micrograms) was injected together with a subliminal dose of poly L-arginine (50 micrograms/paw), a dose-dependent increase in both edema and protein leakage was observed. This effect was selectively inhibited by the anti hnps-PLA2 (10-100 micrograms/paw) but not anti-porc-PLA2 (10-100 micrograms paw). Thus, platelets seem to be involved in both vascular and cellular components of the inflammatory response by contributing, most likely in the early phase, to the edema formation through secretion of PLA2. PMID- 8206647 TI - Growth factor modulation of rat pleural mesothelial cell mitogenesis and collagen synthesis. Effects of epidermal growth factor and platelet-derived factor. AB - This study examined the effects of an epithelial and a mesenchymal growth factor on pleural mesothelial cell proliferation and collagen synthesis, functions that may be important in the response of the pleura to injury. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) added singly caused significant increases relative to control in both the uptake of [3H]thymidine into the cellular DNA of subconfluent monolayers and of [3H]proline into collagenase sensitive protein. Combinations of EGF and PDGF resulted in more than additive increases in proliferation and additive increases in collagen production relative to each factor alone. Media from control and growth factor-stimulated PMC demonstrated no gelatinase or collagenase activity, suggesting that the increase in net collagen production was secondary to enhanced synthesis. These data demonstrate that both epithelial and mesenchymal growth factors can stimulate PMC proliferation and collagen synthesis and that these growth factors have even greater effects when combined, particularly in regard to cellular proliferation. Increases in PMC proliferation and collagen synthesis in response to these growth factors may be important in healing the pleura after injury by a variety of disease processes. PMID- 8206648 TI - Patients with renal cancer have a larger proportion of high-density blood monocytes with increased lucigenin-enhanced chemiluminescence. AB - The production of oxygen metabolites is probably important in cancer cell killing. The production of the superoxide anion, O2-, can be measured by lucigenin-enhanced chemiluminescence (Cl). Previous studies have shown that whole blood lucigenin-enhanced Cl is increased in cancer patients and that this increase is related to blood monocyte activity. The present investigation confirmed these findings and showed that whole-blood lucigenin-enhanced Cl was elevated in 17 patients with renal cell adenocarcinoma (P < 0.001). The activity of the monocytes was studied more in detail, whereby monocytes were separated into different populations based upon differences in densities, i.e., high density and low-density monocytes. The cancer patients had a significantly larger proportion of high-density monocytes (P < 0.05) than controls. The lucigenin enhanced Cl of purified high-density monocytes in controls was significantly higher than that of low-density monocytes (P < 0.01). The authors conclude that the increase in the lucigenin-enhanced Cl of whole blood observed in cancer patients may partly reflect the increased activity of a larger proportion of high density monocytes in these patients. PMID- 8206649 TI - War wounds of bones and external fixation. AB - Missile and explosive limb wounds associated with fractures are common in warfare. The retrieval of function is determined more by the nature of the wound and the wound management than by the method of fracture immobilization. The wound must be managed according to well-proven basic principles and then the advantages and disadvantages of the different methods of fracture immobilization considered for each individual patient. Before embracing external fixation as an indispensable tool for managing war wounds, one must recognize that its popularity in civilian practice is founded on its use for severe open tibial fractures from road trauma. Its principle advantage is to permit access to the soft tissue wound whilst the severity of possible disadvantages is not recognized; its effect on bone healing remains unclear. This review examines the role of external fixation in the management of war wounds and advises caution when considering its widespread or universal use. An approach to war wounds with fractures is described whereby external fixation can be combined with plaster splints or traction; this draws on the advantages of both operative and non operative methods of fracture immobilization and eliminates many of the disadvantages. PMID- 8206650 TI - Risk of occupational glass injury in bar staff. AB - One hundred and twenty-six bar staff (median length of service 2.7 years) working in 42 randomly selected public houses in South Glamorgan were interviewed and examined in the workplace to investigate the incidence, characteristics and treatment of lacerations from bar glassware. 41 per cent reported previous injury, 13 per cent on five or more separate occasions. All injuries but one were of the hand. After 13 per cent of incidents, treatment had been sought in an A & E department, but 58 per cent of incidents causing hand lacerations were not treated. Straight-sided (nonik) one pint (0.6 l) capacity glasses were responsible for two-thirds of injuries, usually during stacking and washing of used glasses. Of bar-workers familiar with toughened glassware, 86 per cent favoured its use on safety grounds. It was concluded that the incidence of sharps (glass) injury was unacceptably high and that this was also a potential cause of cross-infection in this group of workers. PMID- 8206651 TI - 'Doctor, have I got a fracture or a break'? AB - Many patients apparently believe there is a difference between a fracture and a break. In a survey of 100 patients, 81 thought there was a difference. Of these, 71 thought a fracture was better than a break, and 65 believed that bone was undisplaced in a fracture and displaced in a break. These results suggest that greater care, including visual means, should be used in informing patients of their injuries. PMID- 8206652 TI - Motorcycle petrol tanks and their role in severe pelvic injuries. AB - Between 1985 and 1992, nine patients who sustained severe pelvic lesions as a result of motorcycle accidents were admitted to and treated in the authors' department. In six of these nine cases the petrol tank of the motorcycle was one of the wounding agents, and all six patients had the same kind of motorcycle with an oversized petrol tank. All six patients had unstable pelvic lesions. In addition, four had subperitoneal haematomas which required multiple transfusions; five had perineal and/or genital lesions, and one had a ruptured membranous urethra. Severe pelvic injuries are rare, but can have after-effects which jeopardize the social and family life of the patients. A national epidemiological study would be useful to evaluate the frequency of such injuries and to draw conclusions leading to improved safety for motorcyclists. PMID- 8206653 TI - Traumatic duodenal haematoma in children. AB - Over a 15-year period, 967 children presenting to Red Cross War Memorial Children's Hospital with blunt abdominal trauma included nine cases in whom traumatic intramural duodenal haematomas were diagnosed on clinical and radiological grounds. Motor vehicle collisions were the commonest cause of injury. Review of these nine cases and their management confirms the efficacy of non-operative treatment and that laparotomy should be reserved for only those children with additional intra-abdominal injuries, or where the diagnosis remains in doubt. PMID- 8206655 TI - Are air inlets necessary with Haemaccel? AB - Haemaccel is often used for the resuscitation of shocked patients. It is common practice to introduce an air inlet into the plastic container to increase the flow rate. We investigated how much difference an air inlet made. We compared the flow rates with no air inlet, a single air inlet, a 2 x 2 cm hole (equivalent to multiple air inlets) and a pressure infusion cuff. Although the use of an air inlet compared with no air inlet reduced the time to infuse 500 ml by 27 s, the difference was only clinically significant over the final 100 ml. A pressure cuff produced the fastest flow, reducing the time by 68 s. Use of an air inlet, however, precludes subsequent use of a pressure cuff. We recommend that the practice of using air inlets for Haemaccel and other similarly packaged products is abandoned. PMID- 8206654 TI - Diagnostic accuracy in head-injured patients: an emergency department audit. AB - Records of 197 patients admitted to hospital with head injury were studied retrospectively to assess the influence of altered conscious state on injury misdiagnosis in the Emergency department (ED). Diagnostic errors were identified by discrepancies between an initial Injury Severity Score (ISS) calculated according to injuries diagnosed in the ED and a final ISS based on diagnoses confirmed on discharge from hospital, or death. The Glasgow Coma Scale (GCS) was used to assess neurological status. ISS discrepancies were present in 56 patients (29 per cent). These discrepancies arose because of: (i) failure of interpretation of radiographs; (ii) inadequate clinical examination; and (iii) inaccurate injury description in the ED notes. The risk of injury misdiagnosis was greatest for thoracic, abdominal and spinal injury, followed in descending order by extremity (limb), head, and external (skin and subcutaneous) injury. Although there was no linear correlation between GCS and ISS discrepancy rate, ISS discrepancies were significantly more frequent in comatose patients that in non-comatose patients (chi 2 = 3.69, 1 df; P < 0.05). Individual staff performance is at least as important as head injury severity in determining diagnostic accuracy on initial assessment in the ED. PMID- 8206656 TI - Pain and its control in patients with fractures of the femoral neck while awaiting surgery. AB - A survey, by two methods, of the pain felt preoperatively by 100 elderly patients with an acute fracture of the femoral neck showed that most felt a great deal of pain and that a painless fracture was exceptional. No relationship was found between pain appreciation and the patient's fracture type or their age. One of the methods suggested that elderly patients with preserved mental function felt more pain, and the other that less pain was felt by those taking regular prefracture analgesia. The amount of analgesic drugs given to the patients in this survey seemed inadequate for their levels of perceived pain; accordingly regular measurement by nurses of the degree of pain felt preoperatively by patients with this condition is recommended, together with a greater medical review of the medication being prescribed. PMID- 8206657 TI - Preliminary clinical experience with a new fluted humeral nail. AB - The early clinical results of humeral nailing using a fluted intramedullary nail with a locking screw are reported. The True-Flex nail has been designed with a proximal cancellous screw to prevent 'back-tracking' and with flutes to give rotational control. The design features have proved to be successful in the authors' brief clinical experience in 12 patients with complicated fractures, non unions or pathological lesions. Eight of the 10 fractures healed uneventfully, one by delayed union; one had to be revised because of loosening due to use of a nail which was too narrow. There were no serious complications. Return of function in the arm was good. This humeral nail may be suitable for fixation of some complicated and difficult fractures and lesions of the humeral shaft. PMID- 8206658 TI - Collagen organization in the crural interosseous membrane and its relationship to fibular osteotomy. AB - The organization of collagen fibres in the crural interosseous membrane was measured using X-ray diffraction. The fibres were found to be highly aligned and steeply angled in a distal direction from tibia to fibula with a mean angle of 13 degrees. This organization will lead to a very stiff, ligament-like structure which will transmit forces to the tibia generated by the muscles attached to the fibula. It also suggests an optimum site for a fibular osteotomy about 4 cm distal to the tibial fracture site. PMID- 8206659 TI - Complete bilateral amputation of both legs in a 2-year-old child with 10 year follow up. PMID- 8206660 TI - Volar dislocation of the ulna head: torn triangular fibrocartilage demonstrated on MRI scan. PMID- 8206661 TI - Pasteurella tenosynovitis following a dog bite. PMID- 8206662 TI - High-velocity gunshot wound through bone with low energy transfer. PMID- 8206663 TI - Acute acalculous cholecystitis in the critically injured patient--the early sonographic diagnosis. PMID- 8206664 TI - Just a minor neck laceration? PMID- 8206665 TI - Avulsion injury of the subscapularis tendon associated with fracture of the acromion. PMID- 8206666 TI - A case of fractured femoral neck at two levels. PMID- 8206667 TI - Delayed spinal cord damage and a unilateral macular hole following electrical trauma. PMID- 8206668 TI - Pseudorupture of the diaphragm. PMID- 8206669 TI - Previously unrecognized sequelae of anterior cruciate ligament injury. PMID- 8206670 TI - Mothers' active and passive smoking during pregnancy and risk of brain tumours in children. AB - As part of a collaborative study of risk factors for childhood brain tumours, the effects of the mother's smoking and her potential for passive smoking exposure during the pregnancy were assessed in a case-control study. Parents of 91 cases and 321 population controls from Northern Italy, matched for age, sex and residence, were interviewed about their lifetime smoking habits. Mother's smoking during pregnancy was associated with an odds ratio (OR) of 1.7 (95% CI 0.8, 3.8) of brain tumour in her child although this was not statistically significant. Among non-smoking mothers, the risk for light and heavy exposure to passive smoking was 1.7 (0.8, 3.6) and 2.2 (1.1, 4.5) respectively, and a statistically significant dose-response relationship was found (p trend = 0.02). These results must be interpreted within the constraints of the relatively small sample size and the likely misclassification produced by the difference between the potential for exposure to passive smoke and the true exposure. However, they add another piece of information to the growing body of evidence available about the health consequences both of active and of passive smoking and highlight the need for more information about this putative association. PMID- 8206671 TI - Esophageal balloon cytology and subsequent risk of esophageal and gastric-cardia cancer in a high-risk Chinese population. AB - Linxian, China has some of the highest rates of esophageal/gastric cardia cancer in the world. In 1983, esophageal balloon cytology screening was performed in 3 communes in northern Linxian. Of the participants, 10,066 with no evidence of cancer were followed prospectively for 7 1/2 years to evaluate the ability of the initial cytologic diagnoses to identify individuals at increased risk for developing cancer of the esophagus or gastric cardia. A total of 747 incident cases of esophageal or cardia cancer and 322 deaths due to these tumors were identified during the follow-up period and used in this analysis. The risks for esophageal or cardia cancer incidence and mortality increased in parallel with the presumed severity of the 1983 Chinese cytologic diagnoses. After adjusting for potential confounding factors, relative risks for esophageal or cardia cancer incidence, by initial cytologic diagnosis, were normal = 1.00 (reference), hyperplasia = 1.25, dysplasia 1 = 2.20, dysplasia 2 = 4.22 and near-cancer = 5.96. Our results suggest that esophageal balloon cytology, as performed and interpreted in Linxian in 1983, successfully identified individuals at increased risk for developing cancer of the esophagus or gastric cardia. PMID- 8206672 TI - Chromosome aberrations in adenomas of the colon. Proof of trisomy 7 in tumor cells by combined interphase cytogenetics and immunocytochemistry. AB - Thirty-five colon adenomas from 26 patients were analyzed with centromeric probes for chromosomes 1, 7, 17, X and Y in order to study numerical aberrations, chromosome imbalances, aneuploidy and tetraploidization. The fluorescent in situ hybridization (FISH) technique was applied to single-cell suspensions and a combination of FISH and immunocytochemistry (ICC) was employed to identify the cell type under study. Trisomy of chromosome 7 was detected in 37% of the cases. In 7 out of 13 cases this aberration was combined with abnormalities of one or 2 of the other investigated chromosomes. No correlation could be demonstrated between any of the detected chromosomal aberrations and size, localization or degree of epithelial dysplasia. With the combined FISH/ICC procedure, the abnormal cells were shown to be of epithelial rather than of stromal origin. Our data indicate that trisomy 7 is a common chromosome aberration in the epithelial component of colon adenomas. PMID- 8206673 TI - Trends in pancreatic cancer mortality in Europe, 1955-1989. AB - Trends in death certification rates from pancreatic cancer over the period 1955 1989 were analyzed for 25 European countries (excluding the former Soviet Union and a few smaller countries). In 1985-1989, rates for males ranged between 5.3/100,000 (age-standardized world population) in Spain and 10.3/100,000 in Hungary and Czechoslovakia. Other high-mortality areas were located in Northern Europe (Finland, Iceland, Ireland, Denmark) and Central Europe (Austria, Poland, Germany), whilst mortality was lower in Southern Europe (Portugal, Greece). Between 1955 and 1989, mortality rates increased in all the countries considered, the change ranging between 6% in Scotland and 279% in Spain; the rises were higher in the Mediterranean and Eastern European countries than in Northern Europe. Among females, Nordic countries such as Iceland, Sweden and Denmark had the highest mortality rates in 1985-1989 (over 6/100,000) and, as for males, Southern Europe (Spain, Portugal, Greece) appeared as a low-mortality area (around 3/100,000). During the 1955-1989 period, upward trends were observed in all the countries studied, with the highest increase in Greece, Italy, Bulgaria, Poland and Spain. A negative correlation was observed between the percent change in mortality rates between 1955-1959 and 1985-1989 and the rate in 1955-1959 among both males (r = -0.95, p < 0.001) and females (r = -0.81, p < 0.001). Thus, a systematic levelling of rates was observed in most countries, with the exception of the UK and some Nordic countries, whose rates were already high in the late 1950s. Tobacco smoking and dietary factors could account for some of the generalized upward trends. Improved diagnostic and death certification of the disease might also partially explain the observed figures. PMID- 8206674 TI - Gastric cancer in Iceland: a retrospective study of resected gastric specimens in a high-risk country during 30 years (1960-1989). AB - The world-wide incidence of gastric cancer is decreasing, especially in high-risk populations such as the Icelanders. We examined retrospectively 1,040 specimens of resected gastric cancers from a 30-year period, 1960-1989. The decrease in incidence in both sexes involved mainly the largest histological group, the intestinal-type tumours. In males there was also a decrease in diffuse tumours but in females these remained relatively unchanged. Tumours of the antrum and the corpus decreased in both sexes. In males there was a significant increase in tumours of the cardia and most of these were of the intestinal type. In females there was a minor increase in tumours of the cardia, all of which were of the intestinal type. An increase in incidence of tumours of the cardia concomitant with a decrease in incidence of tumours in other parts of the stomach suggests a difference in aetiological factors. The death risk for patients with tumours of the cardia was 59% higher than that for those with tumours in other parts. The death risk following gastric resection was not significantly different when patients with intestinal-type tumours and diffuse tumours were compared. PMID- 8206675 TI - Detection of immunoglobulin heavy-chain gene rearrangement at the single-cell level in malignant lymphomas: no rearrangement is found in Hodgkin and Reed Sternberg cells. AB - Hodgkin and Reed-Sternberg (HRS) cells, the neoplastic cells of Hodgkin's disease (HD), represent only a minority of the cellular infiltrate in affected tissue. Therefore, rearrangements of the immunoglobulin heavy-chain (IgH) gene detected in DNA extracted from an entire Hodgkin's lymph node cannot be attributed to the HRS cells and cannot be used as an argument for the B-cell origin of HRS cells. We developed a new method for the amplification of rearranged DNA of the IgH gene from single cells. Using 6 "forward primers" which were constructed corresponding to consensus sequences of the 6 known families of the IgH variable (V) region (framework region I) and a mix of 2 "reverse primers" corresponding to consensus sequences of the different joining (J) segments, rearrangements of all 6 V families were detected in human peripheral blood lymphocytes. Rearranged IgH DNA could be amplified from single cells of B-cell lymphoma-cell lines and from 13 patients with B-cell non-Hodgkin's lymphomas. However, analysis of HRS cells isolated from lymph nodes of 13 patients with Hodgkin's disease did not show any rearrangement of the IgH gene locus. These findings, obtained by polymerase chain reaction (PCR) on isolated single HRS cells, contrast with previous studies that used Southern-blot analysis of entire tissues affected by Hodgkin's disease. We conclude that the neoplastic HRS cells in Hodgkin's disease--with the possible exception of the nodular paragranuloma subtype--are probably not derived from B cells. PMID- 8206676 TI - Isolation and characterization of tumor-infiltrating lymphocytes from cervical carcinoma. AB - The evidence that virus-induced tumors generally elicit T-cell responses prompts the notion that HPV-related cervical carcinoma would be amenable to treatment by T-cell-mediated adoptive therapy. Therefore, we cultured and cloned tumor infiltrating lymphocytes (TIL) from a patient with cervical carcinoma and studied the in vitro characteristics of these TIL by using the established autologous tumor-cell line. After stimulation of bulk TIL cultures with 1,000 Units/ml recombinant interleukin 2 (rIL-2), followed by limiting dilution, T-cell clones were generated in the presence of 20 U/ml rIL-2 and irradiated autologous tumor cells, PBLs and EBV-transformed B-cell lines. Phenotypically, all clones were CD3/CD8-positive with a heterogeneous CD56 expression. All expressed preferential cytolytic activity against autologous tumor cells, did not lyse autologous lymphoblasts, and were cytotoxic against the NK-sensitive cell line K562. A minor lytic capacity was detectable on allogeneic cervical tumor-cell lines or tumor cell lines of other histologic types. Cytotoxicity against the autologous tumor could be inhibited by anti-CD3, anti-CD8 and anti-ICAM1 but not by anti-HLA class 1 (W6/32, B9.12.1), anti-allele-specific HLA determinants and anti-LFA-3 antibodies. We demonstrate a highly specific autologous lytic activity of cervical carcinoma TIL, in which a CD3-associated surface antigen recognition is involved. These results may prove useful in further studies on adoptive immunotherapy of cervical cancer patients. PMID- 8206677 TI - Metastatic renal-cell carcinoma patients treated with interleukin 2 or interleukin 2 plus interferon gamma: immunological monitoring. AB - We investigated the biological response of 73 patients with metastatic renal-cell carcinoma (MRCC) treated by repetitive weekly cycles of high-dose interleukin 2 (IL-2) (protocol 1, 40 patients) or IL-2 plus interferon-gamma (IFN-gamma) (protocol 2, 33 patients). The objectives of this study were (i) to evaluate the effects of this IL-2 administration schedule on biological response, (ii) to compare the effects of IL-2 alone with those of IL-2 plus IFN-gamma, (iii) to search for any correlation between certain biological marker values and the clinical response to treatment. Mean CD56+ lymphocyte counts (i.e., NK cells) were significantly higher than those of CD3+ cells in the 2 protocols and a subpopulation of CD56bright cells in protocol 1 was found to be preferentially expanded in vivo. Cytotoxic activity against K562 and Daudi cell lines as well as TNF-alpha and sTNF-alpha R (but not IL-6) significantly increased following treatment. Comparison of the data obtained from patients treated with IL-2 alone vs. IL-2 plus IFN-gamma did not show any significant changes except for eosinophilia (higher in protocol 1). Therefore, addition of IFN-gamma did not affect either lymphocyte distribution or non-MHC-restricted cytotoxicity in vivo. No difference in cell subpopulation or cytotoxicity was detected between responders and non-responders. Pre-treatment sTNF-alpha R concentration, in contrast to IL-6 and TNF-alpha, was significantly higher in progressive than in stable and responder groups, suggesting that this parameter may be predictive of the clinical response. PMID- 8206678 TI - Enhancement of radioimmunotherapy by drugs modifying tumour blood flow in a colonic xenograft model. AB - Radioimmunotherapy (RIT) is hampered clinically by poor tumour localization of antibody. In order to enhance localization we have investigated the concomitant use of RIT with 2 drugs, flavone-8-acetic acid (FAA) and its analogue 5,6 dimethylxanthenone-4-acetic acid (XAA), which both reduce tumour blood flow and induce immunomodulation. A single i.v. dose of 0.5 mCi (18.5 MBq) intact 131I anti-CEA antibody significantly delayed growth and prolonged survival over that of untreated controls, in an established LS174T colon xenograft model in nude mice. The adjuvant use of a single i.p. dose of either FAA or XAA, given 24 or 48 hr after 131I-A5B7 to allow maximum tumour levels of antibody to be attained before drug-induced blood-flow inhibition, significantly enhanced the RIT. FAA caused entrapment of antibody within the tumour in relation to the time allowed for localization before drug administration. Repeated doses of FAA prolonged tumour growth inhibition but did not enhance the therapy achieved after a single dose. Although both drugs alone induced massive tumour necrosis of all but a thin peripheral rim of viable cells, tumour regrowth was inhibited for a few days only, with no effect on survival. Drug-induced tumour necrosis, immunomodulation and retention of higher doses of 131I-A5B7 within the tumour may contribute to the enhanced RIT produced by this combined therapy. PMID- 8206680 TI - Analysis of proviral integration in human mammary epithelial cell lines immortalized by retroviral infection with a temperature-sensitive SV40 T-antigen construct. AB - A panel of eight conditionally immortal lines derived by infection of human breast epithelial cells with an amphotropic retrovirus transducing a ts mutant of SV40 large T-antigen was analyzed with respect to individual retroviral integration patterns. Each line contained multiple integration sites which were clonal and stable over extended passage. Similar integration patterns were observed between individual lines arising separately from the same stock of pre immortal cells, suggesting a common progenitor. Retroviral integration analysis of pre-immortal cells at different stages of pre-crisis growth showed changes indicative of a progressive transition from polyclonality to clonality as the cells approached crisis. Each of the immortal lines contained a sub-set of the integration sites of their pre-immortal progenitors, with individual combinations and copy numbers of sites. Since all the cell lines appeared to originate from single foci in separate flasks, it is likely that each set arose from a common clone of pre-immortal cells as the result of separate genetic events. There was no evidence from this analysis to suggest that specific integration sites played any part either in the selection of pre-crisis clones or in the subsequent establishment of immortal lines. PMID- 8206679 TI - Anti-Tac(Fab)-PE40, a recombinant double-chain immunotoxin which kills interleukin-2-receptor-bearing cells and induces complete remission in an in vivo tumor model. AB - We have produced a single plasmid encoding both the heavy chain Fd domain (VH + CH1) of the anti-interleukin-2 receptor (IL2R) monoclonal antibody anti-Tac, and the anti-Tac light chain fused to PE40, a truncated derivative of Pseudomonas exotoxin. The active immunotoxin anti-Tac(Fab)-PE40 could be recovered from E. coli from either periplasm or renatured inclusion bodies. The double-chain immunotoxin was very cytotoxic toward IL2R-bearing cell lines, human activated T cells and fresh adult-T-cell-leukemia cells. The cytotoxicity was similar to that of anti-Tac(Fv)-PE40, the single-chain recombinant toxin containing only the variable domains of anti-Tac. IL2R-binding affinity was also equivalent to that of anti-Tac(Fv)-PE40, which is one-third that of anti-Tac. The serum half-life in mice was significantly prolonged as compared with anti-Tac(Fv)-PE40, with a beta phase of 430 vs. 57 minutes, but the LD50s were equivalent when the immunotoxins were administered in 3 daily doses. Anti-Tac(Fab)-PE40 was very cytotoxic in vitro toward transfected ATAC-4 carcinoma cells which express IL2Rs. In mice bearing ATAC-4 tumors, anti-Tac(Fab)-PE40 showed significant anti-tumor activity, inducing complete remissions in 80 and 100% of treated animals at approximately 7 and 14% respectively of the LD50. Anti-Tac(Fab)-PE40 was much more effective in vitro and in vivo than chemical conjugates between anti-Tac and truncated PE molecules. The recombinant Fab toxin should be studied further as potential treatment for IL2R-related malignancies, particularly if smaller recombinant immunotoxins have insufficient half-life in humans. PMID- 8206681 TI - Evaluation of a new photosensitizer, meso-tetra-hydroxyphenyl-chlorin, for use in photodynamic therapy: a comparison of its photobiological properties with those of two other photosensitizers. AB - The properties of a new photosensitizer, meso-tetra-hydroxyphenyl-chlorin (mTHPC), were studied using V79 cells (Chinese-hamster lung fibroblasts). Comparisons were made with 2 other photosensitizers: photofrin II (PII) and meso tetra-hydroxyphenyl-porphyrin (mTHPP). A main advantage of mTHPC is that it has a strong absorption at 652 nm. Maximal cellular uptake of the dye was observed after 24 hr incubation of the cells with the drug. Using a confocal laser scanning fluorescence microscope, we observed a diffuse distribution of mTHPC in the cytoplasm. Furthermore, the lipophilicity of mTHPC was compared with that of the components of PII by means of high-pressure liquid chromatography (HPLC). Absorption and fluorescence spectroscopy indicated that aggregated as well as monomeric mTHPC was bound to the cells. The action spectrum for photo inactivation of the cells showed that aggregated mTHPC did not contribute significantly to its photosensitizing effects. In the present cellular system, the efficiency of photodynamic therapy (PDT) with mTHPC (cells were irradiated at a wavelength of 652 nm) was higher than with PII (irradiation at 630 nm) or with mTHPP (648 nm). The quantum yield for photo-inactivation of cells was smaller for mTHPC than for mTHPP and PII. The addition of 1,3-diphenylisobenzofuran (DPBF) reduced cell inactivation during PDT. Thus, PDT with mTHPC seems to act at least partly via a type-II process. PMID- 8206682 TI - Caffeine attenuates the action of amsacrine and etoposide in U-937 cells by mechanisms which involve inhibition of RNA synthesis. AB - Pulse treatments of U-937 human promonocytic leukemia cells with the DNA topoisomerase-II inhibitors 4'-(9-acridynilamino)methanesulfon-m-anisidide (amsacrine, mAMSA) or etoposide (VP-16) caused growth inhibition, G2-arrest, increase in cell size and expression of differentiation markers. All these effects were greatly reduced by the presence of 5-10 mM caffeine. In addition, caffeine partially prevented the increase in the number of topoisomerase-DNA cleavable complexes caused by the topoisomerase inhibitors, as determined by SDS/CIK precipitation assays; it caused chromatin condensation, as determined by flow cytometry assays, and interacted with mAMSA in solution, as suggested by spectrophotometric assays. Pulse treatment with caffeine greatly inhibited RNA synthesis but not DNA or protein synthesis, as indicated by labelled precursor incorporation assays. The transcription inhibitor 5,6-dichloro-I-beta-D ribofuranosylbenzymidazole reduced the mAMSA- and VP-16-produced growth inhibition in a similar manner. It is concluded that RNA synthesis inhibition is one of the possible mechanisms by which caffeine protects cells from the action of topoisomerase-II inhibitors. PMID- 8206683 TI - Meta-[211At]astatobenzylguanidine: further evaluation of a potential therapeutic agent. AB - Meta-[211At]astatobenzylguanidine ([211At]MABG) is an astatinated analogue of meta-iodobenzylguanidine (MIBG) that could be of value for therapeutic applications. The initial goal of this study was to determine whether [211At]MABG is taken up, like MIBG, by a specific uptake-I mechanism. Norepinephrine and desipramine (DMI) decreased [211At]MABG uptake in SK-N-SH human neuroblastoma cells. This uptake was found to be energy-dependent: In mice, pre-treatment with DMI reduced uptake of [211At]MABG at 1 hr post-injection in the adrenal and in the heart. Tetrabenazine at a dose of 40 mg/kg reduced uptake of [211At]MABG in the mouse heart in vivo (69% of control) whereas up to 100 microM of tetrabenazine did not affect the in vitro uptake of [211At]MABG in SK-N-SH cells. In SK-N-SH cells, 53% and 38%, respectively, of the initial uptake of [211At]MABG was retained at 4 hr and 6 hr. For no-carrier-added (n.c.a.) [131I]MIBG these values were similar, 60% and 48%. The ability of SK-N-SH cells to incorporate [3H]thymidine was reduced to less than 50% of control values when treated with as little as 3.2 nCi of [211At]MABG. In contrast, no significant reduction in the thymidine uptake was observed, even with 80 nCi of n.c.a. MIBG. PMID- 8206684 TI - Endogenous TGF-beta contributes to the induction of the EBV lytic cycle in two Burkitt lymphoma cell lines. AB - A low proportion of cells in the BL lines P3HR-I and Akata enter spontaneously into the EBV lytic cycle, detectable by the expression of early antigens (EA). We found that both lines produce the active and inactive forms of TGF beta. It was shown earlier that a larger number of cells can be induced to enter the lytic cycle by exposing P3HR-I to phorbol esters and n-butyrate and the surface IgG positive Akata cells to anti-IgG. We now show that the same treatments raise the level of active TGF beta release. Exposure to anti-TGF beta antibodies reduced EA induction by 75-85%. Our results indicate that induction of the viral productive cycle by the above-mentioned reagents is at least partly dependent on the activation of endogenous TGF beta production. PMID- 8206685 TI - Human immunodeficiency virus-1 recombinant gp120 induces changes in protein kinase C isozymes--a preliminary report. AB - Human immunodeficiency virus 1 (HIV-1) and its purified proteins activate target cell functions. Because protein kinase C (PKC) plays a crucial role in signal transduction and there is a molecular heterogeneity of PKC, we compared the effect of recombinant HIV-1 gp120 and phorbol ester (PMA) on PKC isozymes in monocytic U937 cells, with isozyme-specific antibodies using flow cytometry. All PKC isozymes except PKC-gamma were present in U937 cells. Both PMA and HIV-1 gp120 increased levels of calcium-dependent and -independent PKC isozymes. The most striking change was observed in PKC-zeta isozymes levels. This study for the first time demonstrates that HIV-1 gp120 affects calcium-independent PKC isozymes in U937 cells. PMID- 8206686 TI - The in vivo effects of opioid peptides on the murine immune response. AB - We have previously reported that met-enkephalin has dual immunomodulatory properties in vitro. We have continued this investigation using an in vivo system. In this study, Alzet miniosmotic pumps were loaded with either met enkephalin, DTLET or FK 33-824 and were surgically implanted into BAF1/J mice. Twenty-four hours after pump implantation, mice were challenged with sub-optimal, optimal or supraoptimal immunizing doses of antigen. The immune response was assessed 4 or 5 days after primary immunization. FK 33-824, a met-enkephalin analogue, had no effect on the response of mice challenged with a suboptimal antigen dose. However, FK 33-824, at a pump concentration of 10(-3) M, suppressed the response against optimal challenge doses of antigen. At a pump concentration of 10(-8) M, FK 33-824 suppressed, enhanced or had no effect on the supraoptimal antigen dose-induced immune response. The suppressive effect of FK 33-824 in mice immunized with either optimal or supraoptimal doses of antigen was blocked by naloxone. Met-enkephalin and its delta opioid receptor specific analogue, DTLET, had no effect on the immune response to optimal antigen immunization. These results indicate that FK 33-824 has in vivo immunomodulatory activity and provide evidence that opioid peptides may either upregulate or downregulate the in vivo immune response depending on the strength of the response. PMID- 8206687 TI - Efficacy of polyadenylic.polyuridylic acid in the treatment of chronic active hepatitis B. AB - In order to assess whether polyadenylic.polyuridylic acid [poly(A).poly(U)] can be used as a new therapeutic agent for the treatment of chronic hepatitis B, 19 patients with histologically proven chronic active hepatitis B were injected intravenously with 100-150 mg of poly(A).poly(U) weekly for six weeks. Changes in alanine aminotransferase (ALT) levels, 2',5'-oligoadenylate synthetase (2'.5'-AS) activities and HBV markers were sequentially checked during and after treatments. Serum ALT levels were decreased gradually and 2'.5'-AS activities were significantly increased after initiation of poly(A).poly(U) injections. At the end of this trial (24th week) we have observed the normalizations of elevated ALT levels in 14 (73.7%), negative conversion of HBeAg in 11 (57.9%) and loss of HBV DNA in 12 out of 19 patients (63.1%). Complete responses which had both normalization of ALT levels and negative conversion of HBeAg were noted in 11 patients (57.9%) and partial responses showing either normalization of ALT levels or negative conversion of HBeAg alone were in four out of 19 patients (21.1%). No notable adverse effects were observed during the treatments and follow-up period. It can be concluded that poly(A).poly(U) seems to be effective in the treatment of chronic active hepatitis B and has an advantage of being free of significant side effects. PMID- 8206688 TI - Immunopharmacology and toxicology of the plant flavonoid baohuoside-1 in mice. AB - The plant flavonoid baohuoside-1 (B-1), isolated from Epimedium davidii, was shown to suppress antibody and delayed-type hypersensitivity responses in mice in a dose-dependent fashion. By contrast, similar dosage schedules of B-1 did not significantly prolong survival of cardiac grafts. Furthermore, B-1 did not potentiate the effects of the standard anti-rejection drug cyclosporine. Assessment of the mice for appearance, behaviour, biochemistry, haematology and histology revealed no toxic effects at the dosages used in the experiments. These results indicate that the immunosuppressive properties of B-1 are confined to the antibody-mediated system, and suggest that B-1 may be of value in the treatment of chronic inflammatory and autoimmune diseases in which autoantibodies have a major role in pathogenesis. PMID- 8206689 TI - Protective effect of lithium on the stress-induced depression of cell-mediated immunity in mice. AB - The effect of lithium chloride (LiCl) administration on the stress-induced depression of cell-mediated immunity was studied in mice. Two models of stress induced depression of immunity were used: (1) keeping the animals at a temperature of 4 degrees C twice for 24 h at a 24-h interval, and (2) keeping them in the dark for 96 h. Both kinds of stress significantly decreased the reactivity of cell donors in the graft-versus-host (GVH) reaction and recipients in the host-versus-graft (HVG) reaction. Treatment with LiCl of the cell donors in GVH reaction or the recipients in HVG reaction daily for three weeks before stress application completely abolished the immunosuppressive effect of "cooling" stress, but not "darkness" stress. The LiCl is thus shown as a potential immunomodulator protecting mice from some forms of the stress-induced depression of cell-mediated immunity. PMID- 8206690 TI - Engulfment and killing capabilities of neutrophils and phagocytic splenic function in persons occupationally exposed to lead. AB - Phagocytosis and intracellular killing of Candida albicans and Candida pseudotropicalis by neutrophils as well as phagocytic splenic function from lead exposed workers were studied. Two species of Candida were used since in individuals with myeloperoxidase deficiency neutrophils are unable to kill C. albicans, whereas C. pseudotropicalis can be effectively lysed. Phagocytosis with both antigens and phagocytic splenic function were normal in all the workers studied. However, lytic activity towards C. albicans, but not C. pseudotropicalis was impaired. This defect was observed in lead-exposed workers with blood lead levels and urinary delta-aminolevulinic acid (ALA-U) concentrations in the "safe" (below 60 micrograms/dl and 6 mg/l, respectively) and toxic ranges. An impaired ability to kill C. albicans suggests that lead exposure may lead to a myeloperoxidase deficiency. With the exception of blood lead levels and ALA-U concentrations, there was no correlation between any of the other parameters examined. PMID- 8206691 TI - Effect of berbamine on blood and bone-marrow stem cells of cyclophosphamide treated mice. AB - The bisbenzylisoquinoline alkaloid berbamine has been used in China and Japan for the therapy of leukopaenic complications of cancer. Mice treated with non-toxic doses showed significant enhancement of neutrophil and lymphocyte counts in the circulation, but a decrease in the numbers of bone marrow stem cells in a dose dependent manner after two weeks. Similar findings were observed in cyclophosphamide-treated mice. These results indicate that berbamine acts by stimulating the maturation and release of leukocyte progenitors, and may have value in leukopaenic patients. PMID- 8206693 TI - Long-term treatment with 5,5-diphenylhydantoin reduces lymphadenopathy and anti ssDNA autoantibodies in C57BL/6-lpr/lpr mice. AB - To further the insight in the immunomodulating properties of the anticonvulsant 5,5-diphenylhydantoin (DPH), C57BL/6 (B6), C57BL/6-lpr/lpr (B6-lpr/lpr) and MRL/MpJ- +/+ (MRL) mice received DPH orally for six months to determine weekly urinary biopterin levels, a potential T-cell activation marker, by high performance liquid chromatography. At the end of the experiment serum antibody levels were measured by ELISA and relative lymphoid organ weights determined. DPH treatment resulted in reduced body weight in all strains, reduced spleen weights in B6 and MRL mice, profoundly reduced popliteal lymph node weights in B6-lpr/lpr mice and increased thymus weights in MRL mice. DPH treatment decreased serum IgM, IgG and IgA as well as IgM and IgG anti-ssDNA levels in B6-lpr/lpr mice, but did not affect these parameters in other strains. Effects of DPH on IgM rheumatoid factor levels in B6-lpr/lpr mice were inconsistent. Urinary biopterin levels of untreated B6 and B6-lpr/lpr mice were about equal and lower than those of MRL mice. During the first three months of DPH treatment, persistently elevated biopterin levels were observed in B6 and to a lesser degree in MRL mice, and alternately elevated and control levels in B6-lpr/lpr mice. Thereafter, the effects faded in all strains. Results show that long-term DPH treatment causes only minor lymphoid organ weight changes in B6 and MRL mice, but causes a clear reduction of the lymphadenopathy and (auto)antibody formation in B6-lpr/lpr mice. Observed changes could not be related to altered biopterin excretion indicating that the latter is an inappropriate marker of murine autoimmune disease. PMID- 8206692 TI - Suppression of prolactin and cytotoxic T-lymphocyte activity in PCB-treated mice. AB - Halogenated aromatic hydrocarbons (HAH) are ubiquitous environmental contaminants. Studies in rats have shown that HAH treatment can lead to dysregulation of circulating hormone levels, including prolactin. Reduction of prolactin levels in both rats and mice is inhibitory to immune function. Previous studies have reported suppression of alloantigen-specific cytotoxic T-lymphocyte (CTL) activity in mice treated with 3,3', 4,4', 5,5'-hexachlorobiphenyl (HxCB). Here we report that treatment of mice with HxCB (10 mg/kg body weight) leads to a significant reduction of serum prolactin levels (by 89% to 3.7 ng/ml) on day 10 post alloantigen injection (P815 mastocytoma), the day of peak alloantigen specific CTL activity. Prolactin levels were not altered on day 3 post alloantigen injection. Treatment with bromocriptine (5 mg/kg/day) reduced serum prolactin levels slightly on day 3 and significantly (94% to 2.1 ng/ml) on day 10 post alloantigen injection. Splenic CTL activity was not altered by treatment with bromocriptine. The data presented here suggest that reduction of prolactin levels alone, to the extent observed in HxCB-treated mice, is not causative for CTL suppression. PMID- 8206694 TI - Kitson's Therapeutic Nursing Function Indicator as a predictor of the quality of nursing care in hospital wards. AB - This study examines the value of Kitson's (1991) Therapeutic Nursing Function Indicator (TNFI) as a predictor of the quality of nursing care in hospital wards. The TNFI was updated and modified for use in medical and surgical as well as elderly care wards, and was administered to the sister and deputy of 11 wards. Kitson's Therapeutic Nursing Function Matrix (TNFM), which assesses the quality of self-care activities (more precisely, the level of therapeutic nursing), was administered to patients in the first nine wards and was tested for inter-rater reliability. Acceptable reliability was achieved for identification of activities. However, correlations between activity scores were low, although statistically significant. Scores from the modified TNFI were compared with mean TNFM ward scores to test Kitson's finding that the TNFI is a predictor of the quality of nursing; our results did not support this hypothesis. Differences in the design of our study with Kitson's might be responsible for this result. Our analysis, however, suggests that the TNFI has become out of date because of changes in the organisation of nursing work, and that it is no longer a sensitive predictor of the quality of nursing care. PMID- 8206695 TI - Cohabitation of alert residents with cognitively impaired peers in nursing homes: the nursing staff's point of view. AB - The nursing staff's point of view has rarely been examined in regard to the difficulties of cohabitation of alert residents with those who are cognitively impaired. The aims of this study were to assess the nursing staff's preference for mixed or segregated care settings and to identify the factors related to this preference. A systematic sample of 349 nursing staff members working in mixed care settings in 19 nursing homes in Montreal (Canada) completed a questionnaire. There were as many staff members who favored mixed care settings as there were those who preferred segregated settings. A stepwise regression analysis revealed that 46% of the variance is explained by the model, and factors related to staff concerns about residents accounted for 42% of that variance. Notably, staff members who gave a lower rating to the disadvantages for lucid residents living on mixed care units or those who reported more benefits for nonlucid residents living on mixed care units were more in favor of cohabitation. Factors related to staff members' personal concerns explain 3% of the variance. In-service educational strategies are discussed. PMID- 8206696 TI - The international mobility of nurses: a United Kingdom perspective. AB - This paper examines available information on the flows of qualified nurses to and from the United Kingdom, and reports on the results of a questionnaire survey of U.K.-based nurses who had worked abroad. The data examined reveals an upward trend in both "inflow" and "outflow" of nurses in the period 1984-91, with indications of a net outflow. The survey results indicated that Australia was the most common destination; most nurses working abroad had moved to the English speaking countries of North America and Australasia. Barriers and incentives to international mobility of nurses are discussed, and likely future trends in mobility are examined. PMID- 8206697 TI - Criteria formulation and application: an evaluative framework. AB - This paper critically examines how criteria are formulated and applied in quality assurance or quality improvement systems. It begins by drawing attention to the division that exists between criteria derived by so-called expert groups and those developed more locally by practitioners. In seeking to analyse the strengths and weaknesses of these two contrasting approaches, it explores the more fundamental questions of how criteria are formulated in general and how they can best be applied. An evaluative framework is offered as a working checklist for practitioners involved in criteria formulation. The framework identifies three main areas: actual construction of criteria; procedures for formulation and issues related to application. An example of each area is offered from results of the ODySSSy Project. The paper concludes by recommending more systematic studies in this highly complex area. PMID- 8206698 TI - Difficult work: health visitors' work with clients in the community. AB - The purpose of this paper is to discuss health visitors' construction of difficult work as uncovered in their descriptions of actual cases. The grounded theory approach was used to uncover the processes by which health visitors work with clients in the community. Forty-five experienced health visitors participated in the research. Data were collected using semi-structured, conversational interviews, field notes, and a short data collection form. Findings identified three types of situations in their work which created difficulty for health visitors: concerns about client safety, inappropriate use of health visitor services, and client denial and blocking. Several approaches to dealing with difficult situations were identified. These were labelled as: "more of the same", "wait for a bit", "withdrawal", "fall back on routine visiting", "try something else", and "open up the problem situation/confrontation". The use of approaches was related to factors in the context in the situation in which the health visitor found herself, and factors related to the health visitor and her particular style of practice. This paper assists in understanding how health visitors work with clients in the community to influence health. PMID- 8206699 TI - Quality of life in community mental health care--a review. AB - There has been growing interest in the concept and measurement of quality of life in recent years, originally in the field of general health care, and more recently in community mental health. Measures designed to assess quality of life have been used to assess individual clients' problems, to assess the needs of a particular population, or for research purposes. However there is no generally agreed definition of quality of life itself, or of its associated constructs. As a result of this many ways are used to assess quality of life, ranging from those measures which are generally 'objective', using checklists or rating scales, to those which assess quality of life with little or no predetermined structure for the results. The purpose of this selective review is to focus on some of the range of definitions and concepts of quality of life and approaches to its measurement, with a view to illuminating the most appropriate approaches (both for clinical and research purposes) in the field of community care of those with enduring psychiatric illness. PMID- 8206700 TI - Self-disclosure and nursing students: the replication of a Jourard study. AB - A person's willingness to disclose things about him or herself is an important facet of all social interaction. In professional helping relationships effective management of treatment and therapy may depend ultimately on a person's self disclosures. Sidney Jourard claimed in 1971 that "disclosure begets disclosure". It is important therefore to explore professional helpers' willingness to disclose things about themselves, as this may influence the dialogue which they have with their clients and patients. In this paper we describe a replication of a small study carried out by Sidney Jourard in 1961. An opportunistic sample of 25 undergraduate nursing students was asked to complete Jourard's self-disclosure questionnaire. Analysis of the findings suggested that, overall, the students in this study were more self-disclosing than was the case in the earlier study. Other findings are noted as are the limitations of this form of exploration of self-disclosure. PMID- 8206701 TI - A comparison of symptoms used by mothers and nurses to identify an infant with colic. AB - In this survey research a comparison was made between symptoms used by mothers and nurses which led them to think the baby might be "colicky." Two questionnaires, one for mothers and one for nurses, were used to collect the data. The mothers most frequently selected passes gas rectally, clenches fists, draws-up legs, cries late afternoon and evening, holds body straight, and wants to be held. The nurses selected mother states baby is inconsolable, cries more than 4 hours in 24, draws up legs and wants to feed but won't. Parents believed the colic to be related to a variety of factors; these included baby's eating behaviour, maternal anxiety, baby's and mother's diets, and baby's stress. Ten parents reported pain and screaming as symptoms of colic. PMID- 8206702 TI - Function and modulation of expression of auxin-regulated genes. PMID- 8206703 TI - Regulation of mitochondrial gene expression in Saccharomyces cerevisiae. PMID- 8206704 TI - Dynamics of the calcium signal that triggers mammalian egg activation. PMID- 8206706 TI - Cellular mechanisms for the activation of blood coagulation. PMID- 8206705 TI - Regeneration of mammalian retinal pigment epithelium. PMID- 8206707 TI - Analysis of carbohydrate structures in basal laminar deposit in aging human maculae. AB - PURPOSE: To analyze carbohydrate structures in basal laminar deposit (BLD), an extracellular material that accumulates between the retinal pigment epithelium (RPE) and Bruch's membrane. BLD has been shown to correlate positively with visual loss in age-related macular degeneration. METHODS: Thirteen postmortem human maculae with BLD were histochemically examined by light microscopy using the monoclonal antibody HNK-1 and seven lectins; canavalia ensiformis (ConA), soybean agglutinin (SBA), wheat germ agglutinin (WGA), dolichos bifloris (DBA), ulex europaeus (UEA-I), ricinius communis agglutinin I (RCA-I), and peanut agglutinin (PNA). Three maculae were stained with polyclonal antibodies against laminin and collagen type IV. RESULTS: BLD was exclusively stained by DBA and SBA, whereas Con A, WGA, UEA-I, RCA-I, and HNK-1 stained various other structures in the human macula as well. The main part of the BLD adjacent to Bruch's membrane stained with these lectins and the monoclonal antibody HNK-1, whereas only a small part of the BLD adjoining the RPE stained with antibodies against laminin and collagen type IV. Drusen stained neither with any lectin nor with any antibody. CONCLUSIONS: DBA and SBA, which bind specifically to an alpha-D-GalNAc moiety, are specific markers for the light-microscopic detection of BLD in human macular tissue. Furthermore, the authors conclude that BLD contains several carbohydrate structures other than the carbohydrate moieties on laminin and collagen type IV. If drusen contain carbohydrate structures, these must be different from those in BLD. PMID- 8206708 TI - Immunohistochemical localization of L-dopa and aromatic L-amino acid decarboxylase in the rat retina. AB - PURPOSE: The purpose of this study was threefold: to determine if some catecholaminergic amacrine cells of the rat retina use L-DOPA as their neurotransmitter, especially the small (2CA) cells that are immunoreactive to tyrosine hydroxylase but not to dopamine; to understand better the possible existence of serotoninergic cells in the rat retina; and to clarify the role of serotonin in the metabolism of melatonin. METHODS: Immunohistochemistry using antibodies against tyrosine hydroxylase (TH), L-DOPA, aromatic L-amino acid decarboxylase (AADC), dopamine (DA), and tyramine in rat retinal wholemounts, serial sections, and various combinations of double labeling. RESULTS: Paired wholemounts immunoreacted with anti-TH/AADC antibodies did not show a significant difference in densities of TH+ and AADC+ amacrine cells. All the TH+ cells exhibited AADC immunoreactivity. There were no AADC-immunoreactive cells lacking TH. A few TH+ cells exhibited L-DOPA immunoreactivity; they also contained AADC. The inner segments of photoreceptor cells were labeled by the anti-AADC antibody. The antibody to tyramine did not label any cells in the rat retina. CONCLUSIONS: L-DOPA can be excluded as a candidate active substance for the small TH+ amacrine cells that do not exhibit DA-immunoreactivity. The L-DOPA-immunoreactivity restricted to a small number of large TH+ amacrine cells probably does not represent an end product. Tyramine also does not appear to constitute a neurotransmitter in the rat retina. We confirm that there are no serotonin synthesizing amacrine cells in the rat retina. The localization of AADC immunoreactivity in the photoreceptor cell inner segments is possibly related to the biosynthetic pathway of melatonin from 5-hydroxytryptophan. PMID- 8206709 TI - Mitochondrial induction of adult T cell leukemia derived factor (ADF/hTx) after oxidative stresses in retinal pigment epithelial cells. AB - PURPOSE: Adult T cell leukemia derived factor (ADF) is a human homologue of thioredoxin (hTx), which exhibits scavenging activity with reactive oxygen intermediates. In their previous study, the authors found that after transient retinal ischemia, the expression of thioredoxin in rat retinal pigment epithelium (RPE) layer increased markedly. The present investigation is to determine intracellular ADF localization in RPE after transient ischemia and in cultured human RPE cells after oxidative insult by H2O2. METHODS: The authors employed immunoelectron microscopy to examine ADF localization in RPE. Labeling density analysis was performed to supplement the main observation in the experiment of transient retinal ischemia. 3-(4,5-dimethylthiazol-2yl)-2-5-diphenyltetrazolium bromide (MTT) assay was performed to verify the protective role of recombinant ADF (rADF) against H2O2. RESULTS: In immunogold electron microscopy, sparse ADF positive labeling was seen in the cytosol and mitochondria in normal rat RPE and in untreated cultured RPE cells. After oxidative stress, it was concentrated in mitochondria in both groups. MTT assay proved that rADF protected cultured RPE from the toxicity of H2O2. CONCLUSIONS: This study shows the induction of ADF/hTx in mitochondria of RPE after oxidative stresses and its protective effect on cultured RPE exposed to H2O2. The data indicate the possibly important role of ADF/hTx in the protection of retinal cells from the oxidative stresses associated with retinal ischemic disease and probably with regular visual activity. PMID- 8206710 TI - Activin expression by cultured human retinal pigment epithelial cells. AB - PURPOSE: To determine whether human retinal pigment epithelial (hRPE) cells produce activin, a growth factor in the transforming growth factor beta family, and to characterize growth regulatory effects of activin on retinal pigment epithelium. METHODS: mRNA expression was examined using polymerase chain reaction with primers specific for the beta A and beta B chains of activin and by slot blot analysis with a probe specific for the beta A chain. Protein localization was determined immunocytochemically using antibodies specific for the beta A chain of activin and intact activin A. The effect of activin A on DNA synthesis was studied by measuring (3H) thymidine incorporation after cells were exposed to recombinant human activin A (rhA). Growth regulatory effects of rhA on hRPE cells were examined with cell growth assays. RESULTS: beta A mRNA was expressed constitutively in 8/8 cells lines tested. beta B mRNA was not expressed in any of the six cell lines tested but was expressed in human ovarian granulosa cell controls. Positive immunostaining was observed for both the beta A chain and intact activin A. (3H) thymidine incorporation was inhibited 44% (P < 0.025), 45% (P < 0.025), and 44% (P < 0.015) when RPE cells were exposed to 100 ng/ml rhA and grown in serum-free medium, medium with 0.5% serum, and 1% serum, respectively. Cell growth was inhibited 33.2% (P = 0.0001) after RPE cells were exposed to 100 ng/ml rhA for 8 days. CONCLUSIONS: These results suggest that activin A can act as an autocrine-paracrine growth regulator in RPE cells and may help control cellular growth in ocular development and proliferative eye disease. PMID- 8206711 TI - Downregulation of cGMP phosphodiesterase induced by expression of GTPase deficient cone transducin in mouse rod photoreceptors. AB - PURPOSE: Photoexcitation of vertebrate retinal rod photoreceptors stimulates GTP binding to the transducin alpha subunit. Like other GTP-binding proteins, transducin restores itself to an inactive form by hydrolyzing its bound GTP. The role of GTP hydrolysis in phototransduction was investigated. METHODS: A mutant form of cone transducin alpha deficient in its ability to hydrolyze bound GTP was expressed in mouse rod photoreceptors. RESULTS: Expression of the mutant cone transducin alpha at levels threefold to sixfold higher than endogenous rod transducin alpha led to a specific depletion of the transducin target, cGMP phosphodiesterase, and a decrease in the cGMP level. Suction electrode recordings revealed abnormally prolonged flash responses, decreased maximal response amplitudes, and a shift in the stimulus-response relation to higher flash strengths. CONCLUSIONS: Rods expressing high levels of GTPase-deficient cone transduction alpha have reduced levels of phosphodiesterase catalytic subunits and cGMP. These changes are associated with prolonged flash responses, reduced dark current, and decreased sensitivity to light. PMID- 8206712 TI - Rod phototransduction in retinitis pigmentosa: estimation and interpretation of parameters derived from the rod a-wave. AB - PURPOSE: Relationships between the Lamb and Pugh model of transduction in single rod photoreceptors and the parameters derived from human rod a-waves are examined to evaluate transduction abnormalities in retinitis pigmentosa (RP) and cone-rod dystrophy (CRD). METHODS: ERGs were obtained from 15 patients, 11 with RP and 4 with CRD, and from 15 normal subjects. Rod-only responses were derived from responses to blue (W47B) flashes over a wide range of flash energies by computer subtracting estimates of the cone contribution. A model of the rod's response was fitted to the a-waves of the rod-only responses as well as to the responses to the blue flashes by estimating three parameters-sensitivity (S), delay (td), and maximum response (RmP3). To assess the limits of the cone contributions to the parameters of the model, ERGs were obtained from two of the patients, two normal subjects, and three additional patients with nondetectable rod responses using white flashes. RESULTS: All patients had significantly decreased values of RmP3, and eight had significantly decreased values of S compared to the control subjects. The values of the parameters estimated from the responses to the blue flashes were reasonably similar to those for the rod-only responses except in patients with nondetectable rod signals. For the white flashes, the estimate of S was considerably larger and the fit of the model noticeably poorer. CONCLUSIONS: The authors reached two conclusions. First, some forms of RP and CRD alter the activation stages of transduction. Transduction appears normal in other patients, despite extensive receptor damage as indicated by markedly reduced RmP3 values. Second, the cone contribution to a blue flash only affects the estimate of the key parameters in patients in whom the rod component is minimal. The cone contribution to a white flash contaminates the fit and the estimate of the parameters in all patients and normal subjects. PMID- 8206713 TI - Abnormalities of retinal metabolism in diabetes or galactosemia: ATPases and glutathione. AB - PURPOSE: Experimental galactosemia and diabetes are known to result in diabetic like retinopathy in animals, but the mechanism by which the retinopathy develops remains unclear. Defects of retinal metabolism that are common to galactosemia and diabetes are closely associated with the development of retinopathy and might play a role in the pathogenesis of the retinal disease. METHODS: Effects of experimental galactosemia on retinal calcium-activated ATPase [(Ca,Mg)-ATPase], sodium-potassium ATPase [(Na,K)-ATPase], glutathione, ATP, and pertinent ions have been compared with the effects of experimental diabetes in rat and dog models of diabetic retinopathy. RESULTS: Activities of (Ca,Mg)-ATPase and (Na,K) ATPase were decreased as a result of either experimental galactosemia or diabetes in both the dog and the rat, and the decreases were accompanied by a diminution of reduced glutathione (GSH) in the retina. Ouabain-insensitive ATPase activity in the retina was not significantly reduced by diabetes or galactosemia, suggesting that the observed defects in (Ca,Mg)-ATPase and (Na,K)-ATPase activities were specific. The decrease of retinal GSH levels was associated with an elevated concentration of oxidized glutathione in diabetes but not in galactosemia. Retinal ATP and ion concentrations remained unaffected by experimental galactosemia or diabetes. CONCLUSIONS: Comparison of two etiologically dissimilar models of diabetic retinopathy (diabetes and galactosemia) has revealed abnormalities of retinal metabolism that are shared by the two models. Further comparisons of retinal metabolism between these two models should reveal additional sequelae of hyperglycemia that are associated with, and that might play a role in, the development of diabetic retinopathy. PMID- 8206714 TI - Retinal circulatory abnormalities in type 1 diabetes. AB - PURPOSE: To quantify retinal circulatory abnormalities in patients with type 1 diabetes; to 1 diabetes; to compare blood speed and blood flow in major temporal retinal arteries as well as total retinal arterial cross-section measured in patients to that measured in controls without diabetes; to determine which factors are related to the measured abnormalities within the patient group. METHODS: The laser Doppler technique and monochromatic fundus photography were used to measure retinal circulatory parameters in 39 patients with type 1 diabetes with duration of diabetes between 7 and 20 years and 13 age-matched controls without diabetes. Blood pressure, intraocular pressure, and heart rate were measured in all subjects. Glycosylated hemoglobin was measured in the patients. Retinopathy was assessed using standardized color fundus photography and fluorescein angiography. RESULTS: Total retinal arterial cross-section was, on average, 17% higher (P = 0.007) in the patients than in the controls, and it increased with increasing duration of diabetes (P = 0.006). Arterial blood speed was, on average, 33% lower (P = 0.0001) in the patients than in the controls, and it decreased with increasing duration of diabetes (P = 0.03). CONCLUSIONS: The retinal circulation of patients with type 1 diabetes with no retinopathy or background retinopathy is characterized by dilated major arteries with reduced blood speeds. Dilation of the larger retinal arteries, with the accompanying decrease in vascular resistance to flow in those vessels, appears to counteract an increase in resistance to flow at the level of the smaller retinal vessels. PMID- 8206715 TI - Raman spectroscopy of human vitreous in proliferative diabetic retinopathy. AB - PURPOSE: Recent studies have demonstrated increased nonenzymatic glycation in vitreous from patients with diabetic retinopathy. The present study reports the use of Raman spectroscopy as a novel approach for investigating these molecular changes in human vitreous and experimental tissues. METHODS: Near-infrared laser excited Fourier-transform (FT) Raman spectroscopy (RS) was performed on vitreous specimens obtained at surgery from seven patients with proliferative diabetic retinopathy and from 10 controls. Measurements were also obtained from samples of control and glycated (in vitro) rat tail tendon collagen and demineralized chick bone collagen. RESULTS: Spectroscopy of vitreous samples from patients with diabetic retinopathy revealed two prominent peaks at 1604 cm-1 and 3057 cm-1, corresponding to aromatic C = C and C-H stretching vibrations in pi-conjugated and aromatic molecules. The peak at 1604 cm-1 was threefold higher in vitreous from patients with diabetes than from controls. Spectra obtained from experimental tissues provided evidence suggesting that the results obtained in human vitreous may be due to nonenzymatic glycation and not to the lysyl oxidase pathway. CONCLUSIONS: These findings suggest that human vitreous obtained from subjects with diabetes may be distinguished from control vitreous by FT-RS and that the peaks characterizing the diabetic samples are possibly due to nonenzymatic glycation. Raman spectroscopy may provide a useful method to elucidate the molecular events underlying these abnormalities. PMID- 8206716 TI - Similarities in regulation of the HSV-1 LAT promoter in corneal and neuronal cells. AB - PURPOSE: To address the possibility of neuronal-like herpes simplex virus type 1 (HSV-1) latency in the cornea by determining if regulation of the HSV-1 LAT promoter in stromal keratocytes is similar to LAT promoter regulation in neurons. METHODS: Transient chloramphenicol acetyltransferase (CAT) assays were used to measure the relative promoter activity of various HSV-1 LAT promoter fragments in primary human corneal cells versus neuronal and nonneuronal cells. RESULTS: The authors found that the LAT promoter, whose location they previously mapped in neurons using transient CAT assays, functioned in stromal keratocytes using the same assay system and that two regions between -283 and -1932 nucleotides relative (upstream) to the start of LAT transcription slightly increased the LAT promoter activity in stromal keratocytes. They previously showed a similar increase in neuronal cells, and a large decrease in nonneuronal cells. In addition, they found that a neuronal specific enhancer region they previously defined between -162 and -283 nucleotides upstream of the start of LAT transcription also enhanced promoter activity in stromal keratocytes. Using gel shift assays, they detected a nuclear factor specific to neurons and stromal keratocytes that binds to the LAT promoter and that may be a LAT regulatory factor. CONCLUSIONS: Recently, it has been suggested that the cornea might serve as an alternative site of latent herpes simplex virus type 1 (HSV-1) infection. However, this remains controversial. The authors' findings suggest that corneal and neuronal cells regulate the LAT promoter similarly and that this regulation differs from that seen in nonneuronal cells. Thus, the possibility of neuronal like latency in the cornea remains plausible. PMID- 8206717 TI - Temporal tuning and the development of lateral interactions in the human visual system. AB - PURPOSE: The authors examined the development of lateral interactions between neurons in the human visual system through the use of visual evoked potentials (VEPs) elicited by windmill-dartboard stimuli. Previously, these VEPs have revealed two distinct types of lateral interactions (short-range and long-range) in adults. This study aims to track the development of these interactions in the first 6 months of life. METHOD: Windmill-dartboard stimuli were generated by a computer-controlled visual stimulator and presented on an oscilloscope display. VEPs to these stimuli were obtained from a group of human infants between 14 days and 6 months of age and from a group of adults who served as a basis for comparison. Fourier analysis was used to retrieve amplitude and phase measures of the relevant frequency components of the response. RESULTS: Amplitude measures of the VEP components elicited by the windmill-dartboard stimulus showed that the attenuation of the second harmonic frequency component (reflecting long-range lateral interactions) was essentially adultlike at all temporal frequencies for the majority of infants. In contrast, the amplitude of the fundamental frequency component (thought to reflect short-range lateral interactions) exhibited a low pass temporal tuning function in infants that differed dramatically from adults. Additional immaturities were observable in the phase of the fundamental component of the infant VEPs. CONCLUSIONS: Evidence for the presence of some degree of lateral interaction was seen in even the youngest infant. Long-range lateral interactions appear to mature rapidly in infancy, whereas short-range lateral interactions show a much longer developmental time-course, and their properties are dependent on temporal frequency. PMID- 8206718 TI - HIV-related ocular microangiopathic syndrome and color contrast sensitivity. AB - PURPOSE: Color vision deficits in patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) disease were reported, and a retinal pathogenic mechanism was proposed. The purpose of this study was to evaluate the association of color vision deficits with HIV-related retinal microangiopathy. METHODS: A computer graphics system was used to measure protan, deutan, and tritan color contrast sensitivity (CCS) thresholds in 60 HIV-infected patients. Retinal microangiopathy was measured by counting the number of cotton wool spots, and conjunctival blood-flow sludging was determined. Additional predictors were CD4+ count, age, time on aerosolized pentamidine, time on zidovudine, and Walter Reed staging. The relative influence of each predictor was calculated by stepwise multiple regression analysis (inclusion criterion; incremental P value = < 0.05) using data for the right eyes (RE). The results were validated by using data for the left eyes (LE) and both eyes (BE). RESULTS: The only included predictors in multiple regression analyses for the RE were number of cotton-wool spots (tritan: R = .70; deutan: R = .46; and protan: R = .58; P < .0001 for all axes) and age (tritan: increment of R [Ri] = .05, P = .002; deutan: Ri = .10, P = .004; and protan: Ri = .05, P = .002). The predictors time on zidovudine (Ri = .05, P = .002) and Walter Reed staging (Ri = .03, P = .01) were additionally included in multiple regression analysis for tritan LE. The results for deutan LE were comparable to those for the RE. In the analysis for protan LE, the only included predictor was number of cotton-wool spots. In the analyses for BE, no further predictors were included. The predictors Walter Reed staging and CD4+ count showed a significant association with all three criteria in univariate analysis. Additionally, tritan CCS was significantly associated with conjunctival blood-flow sludging. CONCLUSION: CCS deficits in patients with HIV disease are primarily associated with the number of cotton-wool spots. Results of this study are in accordance with the hypothesis that CCS deficits are in a relevant part caused by neuroretinal damage secondary to HIV related microangiopathy. PMID- 8206719 TI - Corneal tensile strength in fully healed radial keratotomy wounds. AB - PURPOSE: To investigate the susceptibility to rupture of a human donor cornea with fully healed radial keratotomy (RK) incisions using biomechanical measurement methods and finite element analysis. METHODS: A human cornea 8 years after RK was cut into four strips and subjected to tensile testing until rupture occurred. The fellow cornea was pressurized on an artificial anterior chamber beyond the initiation of wound gape. The tensile strengths of nine strips from unincised corneas were measured as controls. To investigate the effect of epithelial plugs on the RK strip test results, a finite element model of a strip containing an epithelial plug was analyzed. RESULTS: Rupture occurred along the wound site with wide variability in the measured tensile strengths. There was no significant difference in tensile strength between the RK corneal strips (16.6 +/ 4.43 N/mm2) and the control strips (19.1 +/- 3.50 N/mm2). Four of the eight incisions of the fellow RK cornea gaped, but the cornea did not rupture up to a pressure of 2740 mm Hg. An epithelial plug of 10% of the corneal thickness was found in one of the incisions. The finite element results demonstrated higher stresses at the wound site that increased with the size of the epithelial plug. CONCLUSIONS: The presence of an epithelial plug in a fully healed radial keratotomy incision will create a stress concentration at the incision site that may predispose the cornea to rupture. The variability in the strength measurements indicates that the increase in rupture susceptibility due to RK may be hard to predict and may depend on factors such as the size of the plug and the strength of the wound collagen. PMID- 8206720 TI - Intraocular photodisruption with picosecond and nanosecond laser pulses: tissue effects in cornea, lens, and retina. AB - PURPOSE: Nd:YAG laser photodisruption with nanosecond (ns) pulses in the millijoule range is an established tool for intraocular surgery. This study investigates tissue effects in cornea, lens, and retina to assess whether picosecond (ps) pulses with energies in the microjoule range can increase the surgical precision, reduce collateral damage, and allow applications requiring more localized tissue effects than can be achieved with ns pulses. METHODS: Both ps and ns Nd:YAG laser effects on Descemet's membrane, in the corneal stroma, in the lens, and at the retina were investigated in vitro in bovine and sheep eyes and in cataractous human lens nuclei. For each tissue, the optical breakdown threshold was determined. The morphology of the tissue effects and the damage range of the laser pulses were examined by light and scanning electron microscopy. The cavitation bubble dynamics during the formation of corneal intrastromal laser effects were documented by time-resolved photography. RESULTS: The optical breakdown threshold for ps pulses in clear cornea, lens, and vitreous is, on average, 12 times lower than that for ns pulses. In cataractous lens nuclei, it is lower by a factor of 7. Using ps pulses, Descemet's membrane could be dissected with fewer disruptive side effects than with ns pulses, whereby the damage range decreased by a factor of 3. The range for retinal damage was only 0.5 mm when 200 microJ ps pulses were focused into the vitreous. Picosecond pulses could be used for corneal intrastromal tissue evaporation without damaging the corneal epithelium or endothelium, when the pulses were applied in the anterior part of the stroma. The range for endothelial damage was 150 microns at 80 microJ pulse energy. Intrastromal corneal refractive surgery is compromised by the laser-induced cavitation effects. Tissue displacement during bubble expansion is more pronounced than tissue evaporation, and irregular bubble formation creates difficulties in producing predictable refractive changes. CONCLUSIONS: The use of ps pulses improves the precision of intraocular Nd:YAG laser surgery and diminishes unwanted disruptive side effects, thereby widening the field of potential applications. Promising fields for further studies are intrastromal corneal refractive surgery, cataract fragmentation, membrane cutting, and vitreolysis close to the retina. PMID- 8206721 TI - Tear fluid plasmin activity after excimer laser photorefractive keratectomy. AB - PURPOSE: Elevated tear fluid plasmin activity may correlate with delayed healing of corneal wounds. The present study was performed to establish the tear fluid plasmin activity after photorefractive keratoablation (PRK). METHODS: Tear fluid aspirated with microcapillaries was subjected to a fluorometric plasmin assay using the 7-amido-4-trifluoromethylcoumarin derivate of the tripeptide H-D-Val Leu-Lys as substrate. RESULTS: Tear fluid flow, plasmin activity, and flow corrected plasmin excretion rate in tears (plasmin flux) were determined preoperatively and 1, 2, and 7 days after PRK. The preoperative tear fluid flow was 6.55 microliters/min (median; range, 1.8 to 21.8 microliters/min), plasmin activity was 1.29 IU/l (median; range, 0.6 to 6.9 IU/l), and the excretion of plasmin in tears was 11.7 microIU/min (median; range, 1.6 to 41.5 microIU). A statistically significant decrease in tear fluid plasmin activity was found during the follow-up period on the first (0.6 IU/l; range, 0.6 to 1.7 IU/l, P < 0.01) and second (0.65 IU/l; range, 0.6 to 1.49 IU/l, P < 0.01) postoperative days. On the other hand, significant elevation of both tear fluid flow and plasmin flux values occurred during the first two postoperative days. The median plasmin flux values on days 1, 2, and 7 were 57.35 microIU/min (range, 16 to 540 microIU/min, P < 0.01), 40.0 microIU/min (range, 13.3 to 222.8 microIU/min, P < 0.01), and 10.2 microIU/min (range, 2.2 to 90.7 microIU/min, P > 0.05), respectively. CONCLUSION: The marked elevation of tear fluid flow coincided with the persistence of an epithelial defect. However, because of the acceleration of tear fluid flow, proteolytic activity due to plasmin (IU/l) actually decreases. Consequently, the increased excretion of plasmin in tears (plasmin flux) does not lead to highly elevated plasmin activity, which could inhibit wound healing. It seems to be a natural healing response because all corneas were epithelialized normally by or on day 3. PMID- 8206722 TI - Eosinophil granule major basic protein inhibition of corneal epithelial wound healing. AB - PURPOSE: Human eosinophil major basic protein (MBP) was studied in an established organ culture model for rat corneal epithelial wound healing to elucidate further the role of the protein in vernal keratopathy. METHODS: Epithelial migration rates were tested for five MBP concentrations (10, 25, 50, 100, and 200 micrograms/ml MBP). RESULTS: Significantly less epithelial migration than control (P < 0.05) was observed in all tested groups. Histologic examination revealed abnormally heaped-up leading epithelial edges in all test groups compared to the normal tapered edges in all controls. Immunofluorescence disclosed MBP deposition on deepithelialized cornea. CONCLUSIONS: These results suggest that MBP may contribute to vernal corneal ulcerations by inhibiting corneal epithelial migration. PMID- 8206724 TI - Transcriptional control of human Tenon's capsule fibroblast collagen synthesis in vitro by gamma-interferon. AB - PURPOSE: Gamma-interferon (gamma-IFN) has been shown to be a potent inhibitor of collagenous protein production independent of its effects on noncollagenous protein production and cell proliferation in vitro. To understand further the processes controlling tissue fibrosis and the potential use of gamma-IFN as an antifibrotic treatment after glaucoma filtering surgery, the in vitro effects of recombinant gamma-IFN on procollagen mRNA production were studied. METHODS: Subconfluent human Tenon's capsule fibroblast cultures were exposed to 10, 50, 500, and 1000 U/ml of human recombinant gamma-IFN for 48 hours and to 500 U/ml for 12, 24, and 72 hours. After the incubation period, polyA+ mRNAs were isolated by oligo (dT) cellulose columns, separated according to size by electrophoresis through a denaturing agarose gel, and transferred to an activated nylon membrane for Northern blot analysis. The levels of type III (alpha 1) procollagen, type I (alpha 1) procollagen, and fibronectin (noncollagenous protein) mRNA were determined by hybridization with radiolabeled cDNA probes specific for these components followed by autoradiography. RESULTS: Densitometric analysis showed gamma-IFN selectively inhibited type III and type I procollagen mRNA synthesis from 24% (10 U/ml) to 99% (1000 U/ml) while leaving fibronectin mRNA synthesis unaffected. The degree of inhibition was also time dependent; more inhibition occurred with increasing incubation time. CONCLUSIONS: These results indicate that gamma-IFN is able to regulate collagen synthesis at the transcriptional level and that its inhibition is relatively specific. Gamma-interferon's specific inhibitory effects may offer advantages over current therapies in modulating the fibrotic response after glaucoma filtering surgery. PMID- 8206723 TI - Immunoprecipitation of A1 adenosine receptor-GTP-binding protein complexes in ciliary epithelial cells. AB - PURPOSE: To examine the interaction of alpha subunits of guanine nucleotide binding proteins with A1 adenosine receptors from the SV40-transformed bovine derived pigmented (PE) and human-derived nonpigmented (NPE) ciliary epithelial cell lines using an immunoprecipitation approach and [3H]DPCPX, a selective radioligand to adenosine receptor. METHODS: Solubilized preparations of adenosine receptors from PE and NPE cell lines were immunoprecipitated with G protein specific antisera 8730 (anti-Gi alpha), 3646 (anti-Gi alpha 1), 1521 (anti-Gi alpha 2), and 1518 (anti-Gi alpha 3), and of adenosine receptor-G protein complexes were detected by the binding of radioactive [3H]DPCPX. RESULTS: Data indicate that [3H]DPCPX forms high-affinity complex with membrane-bound and solubilized forms of adenosine receptors from PE and NPE cells. Peptide-directed antisera against various G protein alpha subunits indicate that the A1 adenosine receptors from these cells are specifically coupled to Gi alpha complexes. The results further indicate that the A1 adenosine receptors are predominantly associated to Gi alpha-3. CONCLUSION: The findings document a selective interaction between the alpha subunits of the inhibitory guanine nucleotide binding protein (Gi) and A1 adenosine receptors in ocular ciliary epithelial cells in culture. The results suggest that adenosine receptors coupled to Gi alpha-3 may provide a site at which modulation of aqueous humor production in the ciliary epithelium occurs via the G protein-adenylyl cyclase pathway. PMID- 8206725 TI - Morphology and function of the corneal endothelium after long-term contact lens wear. AB - PURPOSE: To examine whether corneal hydration control is impaired in corneas with endothelial morphologic changes (increased variation in cell size and cell angularity) due to long-term low gas-permeable contact lens wear. METHODS: Twenty one long-term wearers of low gas-permeable contact lenses (mean age, 41 years +/- 8 SD) and 18 age-matched controls (mean age, 42 years +/- 8 SD) were studied. To assess endothelial morphology, endothelial photographs were taken, enlarged 400X, scanned into a computer, and evaluated. Hydration control was assessed by a corneal stress test. Corneal swelling was induced by applying low gas-permeable soft contact lenses for 2 hours during eye closure. After the lenses were removed, the rate of deswelling was determined using optic pachometry. RESULTS: Morphologic analysis of the endothelial photographs showed a significant increase of polymegethism (P < 0.01) and pleomorphism (P < 0.01) in the group wearing contact lenses compared with the control group. The percentage of recovery of corneal thickness per hour (PRPH) from induced swelling proved to be significantly lower (P = 0.03) and the induced swelling proved to be significantly lower (P < 0.01) in the group wearing contact lenses than in the control group. Multiple regression analysis showed that the PRPH decreased as the morphologic alterations increased. However, this trend appeared not to be significant at the 5% level. A significant relationship was found between morphologic parameters and induced swelling, indicating that induced swelling decreased as the morphologic alterations increased. CONCLUSION: The results of this study indicate that increased endothelial polymegethism and pleomorphism may be accompanied by a decreased corneal hydration control in people who wear contact lenses. PMID- 8206726 TI - Reproducibility of the NEI Scheimpflug Cataract Imaging System. AB - PURPOSE: The NEI Scheimpflug Cataract Imaging System was developed to allow for easy, accurate and reproducible image analysis of nuclear cataracts. This study was undertaken to determine the reproducibility of densitometric measurements of the lens nucleus using this modified system. METHODS: Replicate Zeiss Scheimpflug images of the lenses in 143 eyes were obtained by one photographer. Normal and cataractous lenses (without central cortical or anterior subcapsular opacities) were sampled. Images were stored after testing for adequacy using immediate exposure checking. Densitometry of the nuclear region was then performed for each image. The interval within which 99% of the differences between repeat measurements may be expected to lie was used as a measure of reproducibility (99% range). RESULTS: A 99% range of +/- 0.023 optical density units (odu) was obtained for nuclear densities < 0.30 odu (125 eyes). For lenses with nuclear densities > or = 0.30 odu (18 eyes), the 99% range was +/- 0.14 times the first measurement. CONCLUSION: This study shows the excellent reproducibility of this Scheimpflug imaging system in the nuclear region and demonstrates its usefulness in studies on nuclear cataracts, particularly for natural history studies and clinical trials of anti-cataract drugs. PMID- 8206727 TI - The immune response and the eye: the ACAID inducing signal is dependent on the nature of the antigen. AB - PURPOSE: To examine conditions that determine the nature of the blood-borne, ACAID-inducing signal produced after intracameral injection of antigen. METHODS: Balb/c mice were splenectomized, rested, and injected in the anterior chamber with various antigens. Two days later the animals were bled, the plasma and white cells were isolated, and these fractions were transferred to naive mice (with spleens). Recipients were immunized subcutaneously within 2 to 7 days and delayed type hypersensitivity was assessed 10 to 14 days after immunization by challenge with the appropriate antigen. RESULTS: The antigens HSV-1, TNP-coupled cells, and P815 tumors cells induced a soluble ACAID-inducing signal found in the plasma portion of blood. The soluble protein antigens bovine serum albumin (BSA) and conalbumin induced a cell-associated signal. When T-cells were included with protein antigens, a soluble (not cellular) ACAID-inducing signal was induced. CONCLUSIONS: Particulate antigens, such as HSV-1 and P815, that elicit intraocular T-cell responses or antigens that contain T-cells (e.g., TNP cells) induce a soluble, ACAID-inducing signal. Soluble antigens (e.g., BSA and conalbumin) induce a cell-associated ACAID signal. Additionally, T-cells are capable of modulating the type of ACAID signal produced. These results show that two methods of delivering the ACAID signal exist that are dependent on the nature of the antigen and the presence of T-cells. The authors conclude that the eye shows great versatility in regulating potentially damaging immune responses. PMID- 8206728 TI - Propagation and immortalization of human lens epithelial cells in culture. AB - PURPOSE: To establish primary and immortalized cell cultures of human lens epithelial cells for a model system investigating human lens epithelial physiology and cataract. METHODS: Human lens epithelial cells in culture were grown by isolating epithelium fragments from infant human lenses from patients who underwent treatment for retinopathy of prematurity and by allowing epithelial cells to grow from explants. To immortalize cells, the cultures were infected with an adenovirus 12-SV40 virus (Ad12-SV40). RESULTS: The primary cells from infant eyes proliferated for three passages before senescence was observed. However, the immortalized cells remained proliferative and retained the morphology of the primary cells. Immunohistochemical analysis demonstrated that these immortalized cells were SV40 large T antigen-positive and ceased to produce infectious virus after a few passages. Immortalized cells passaged to population doubling levels of 76 continued to form confluent cultures within 7 days of subculture. Analysis of proteins by SDS-PAGE and immunoblotting showed that immortalized cells produce a protein with molecular weight of about 25 kD, which reacted with an antibody to beta H-crystallin. CONCLUSIONS: This report constitutes the first successful immortalization of human lens epithelial cells. Currently, two cell lines have been created (B-3 and B-4) and passaged to population doubling levels of 76 and 52, respectively. These cells may provide an important human cell line specific to in vivo human lens epithelial cell physiology and would be of interest in establishing a human model to study lens cell differentiation and the etiology of cataract. These cells may also provide a constant and reproducible source of lens epithelial cells for eye-related toxicology studies and to assay inhibitory drugs for the prevention of cataracts and posterior capsular opacification observed after cataract extraction. PMID- 8206729 TI - Fibrillin and elastin networks in extrafusal tissue and muscle spindles of bovine extraocular muscles. AB - PURPOSE: Bovine extraocular rectus muscles were examined to map the distribution of elastin and fibrillin in extrafusal tissue and muscle spindles. METHODS: Immunohistochemical techniques and immunolocalization were employed to pin-point the placement of molecules relative to muscle fibers. RESULTS: Strands containing elastin and fibrillin surrounded all extrafusal fibers. They also covered the external surface of intrafusal fibers, more extensively at the equator than at the pole. Within strands elastin was placed in the center, whereas fibrillin was located in microfibrils on the periphery. CONCLUSIONS: The wide distribution in extrafusal tissue of elastin and fibrillin suggests that they are factors in determining the mechanical properties of extraocular muscles. Their placement in proximity to individual intrafusal fibers should affect the viscoelastic properties of these fibers and, thus, influence the dimensions of the afferent discharge. PMID- 8206730 TI - Detection efficiency of circular gratings and bandpass filtered points with randomized phase spectra. AB - PURPOSE: In the studies of spatial integration an increase in the spatial extent of the stimulus usually results in a decrease in the spatial frequency bandwidth of the stimulus. The authors investigated separately the effects of these two factors on contrast detectability. METHODS: Efficiencies were measured for a circular grating at 4 c/deg and for bandpass-filtered point stimuli having a constant center frequency at 4 c/deg and bandwidths of 0.25, 0.5, 1, and 2 octaves. The phase range of these two-dimensional stimuli was increased from zero to 90, 180, 270, and 360 degrees by replacing the original zero phase at each spatial frequency component by a random number with zero mean. This procedure left the spatial frequency bandwidth unaffected. RESULTS: The increase in phase range and decrease in spatial frequency bandwidth caused a progressively larger proportion of the contrast energy of the point stimuli to spread into their surroundings. As a result, detection efficiency decreased with increasing bandwidth and phase range for all point stimuli. However, a change in the stimulus bandwidth affected efficiency only when it altered stimulus area. The area of the circular grating and its detection efficiency remained almost constant irrespective of the phase range. When efficiency was plotted in semi logarithmic coordinates as a function of stimulus area expressed in terms of the spatial spread of contrast energy, the line of least squares explained 85% of the total variance. CONCLUSION: The primary determinant of detection efficiency for stimuli with constant center spatial frequency is not stimulus bandwidth but stimulus area expressed in terms of the spatial spread of contrast energy. PMID- 8206731 TI - Electroretinographic study of the C57BL/6-mivit/mivit mouse model of retinal degeneration. AB - PURPOSE: The C57BL/6-mivit/mivit mouse model of retinal degeneration is characterized by slow progressive loss of photoreceptor cells, concomitant loss of rhodopsin, and uneven pigmentation of the retinal pigment epithelium. The purpose of this study was to determine how these alterations affected the electroretinogram (ERG). METHODS: Scotopic ERGs were measured in two litters of mivit/mivit mice beginning at 4 weeks and continued in the same animals at 2-week intervals through 18 weeks. RESULTS: The mean of the maximum b-wave amplitude (Vmax) at 4 weeks was 234 +/- 14 microV in mivit/mivit mice, which did not differ significantly from controls (266 +/- 26 microV). With increasing age, all components of the ERG decreased and by 12 weeks, the mean of the Vmax had decreased to 170 microV. At 18 weeks, the mean Vmax was 75 microV, and the b- to a-wave ratio was still > 1.0. Comparison of these physiologic data to previously reported morphologic and biochemical data showed a high correlation between the b wave amplitude and the number of photoreceptor cell nuclei (r = 0.9772) as well as the b-wave amplitude and rhodopsin levels (r = 0.9019). CONCLUSIONS: The loss of all components of the ERG and the lack of a negative-type ERG suggested that the primary cells altered in the mivit/mivit mouse were the photoreceptors. The high correlations between the ERG amplitude and the number of photoreceptor nuclei indicate that the Vmax of the ERG is a good measure of the degree of photoreceptor loss. PMID- 8206732 TI - Israeli adolescents' norms of the Brief Symptom Inventory (BSI). AB - The internal consistency and concurrent validity of a Hebrew version of Derogatis' Brief Symptom Index (BSI) were assessed in a sample of 840 high school students from three different towns in Israel. The results show high levels of internal consistency and good concurrent validity of the Hebrew version. The type of high school and the country of origin of the subjects' parents had no significant effect on BSI scores. Differences between Israeli and US subjects are reported. BSI norms presented in this study might be used in further studies in Israel. PMID- 8206733 TI - Boundaries during adolescence. AB - This essay looks at the period of adolescence through the dimension of boundaries and examines how adolescence and boundaries affect one another. During adolescence external physical and internal psychological boundaries are blurred. The climate and milieu are well defined and having the environment provide clear boundaries facilitates the passage of this developmental stage. PMID- 8206734 TI - Child and adolescent psychiatry and aggression. PMID- 8206735 TI - Countertransference to parents in child psychotherapy. AB - The author refers in this paper to countertransference to parents of children in treatment, within the conceptual framework of Racker's (1) terms concordant and complementary countertransference. In the second part of the paper the author demonstrates that the use of the concept counter-transference to somebody who is not the actual patient has theoretical basis. It is then hypothesized that the simultaneous analysis of the types of countertransference to the parent and to the child might reveal important information regarding the developmental place of the child, and thus, help the therapist in the child's treatment. PMID- 8206736 TI - Brief strategic therapy in a child community clinic. A follow-up report. AB - This paper reports the outcome of brief strategic therapy, practiced according to the model described by S. de Shazer, in an out-patient child psychiatry clinic during 4 years. Forty-two clients were interviewed in a span of 6 to 18 months after termination of therapy and asked about symptomatic improvement and satisfaction with the treatment. The results showed that brief strategic therapy achieved lasting complaint resolution in a high percentage of cases, high satisfaction rates with little relapse or need for additional interventions. PMID- 8206737 TI - Aggression expression in grandchildren of Holocaust survivors--a comparative study. AB - Ninety-seven Israeli children (59 girls and 38 boys), with a mean age 10.1 +/- 1.9, participated in this study. Fifty-four of them were grandchildren of Holocaust survivors, and 43 were controls. All subjects were administered the EAS, a projective test designed to assess the extent of externalization of aggression in reaction to frustrating events. Grandchildren of Holocaust survivors did not differ in their expression of aggression from controls. As difficulties in externalizing aggression are considered in the literature to be a central factor in the maladaptation of survivors and subsequently in their sons and daughters, the results of the present study were interpreted to be one possible indication that transgenerational transmission of trauma has ceased in the third generation. PMID- 8206738 TI - Post-traumatic stress disorder in myocardial infarction patients: prevalence study. AB - This study examined the prevalence of post-traumatic stress disorder (PTSD) in a sample of 100 Israeli myocardial infarction (MI) patients. Chronic PTSD was diagnosed in 16% of these patients and acute (PTSD) in 9%. The appearance of PTSD following MI was found to be related to the following variables: ethnic background; prior traumatic experiences, including prior MI; and anticipation of disability following MI. Objective measures of MI severity were not related to propensity to develop PTSD. The presence of PTSD correlated with self reports of dysfunction in these MI patients and may account for the majority of failures in rehabilitation. PMID- 8206739 TI - Israeli norms for the Achenbach Child Behavior Checklist: comparison of clinically-referred and non-referred children. AB - This paper presents the Israeli norms for the Achenbach Child Behavior Checklist. Questionnaire data were collected on a clinically-referred sample (N = 2227) and a non-referred sample (N = 1275) of children between the ages of 4-16. Basic descriptive data for total behavior scores and scores for broad-band and narrow band syndromes by sex, age group, and clinical status are presented. The mean total behavior score in the non-referred sample is similar to that reported for American and Dutch samples. For the Israeli referred sample, the mean total behavior score was considerably lower than that reported for the American and Dutch samples. Issues involved in selecting an optimal cutoff point to discriminate between clinically-referred and non-referred populations are discussed. PMID- 8206741 TI - On the use of 2,4,5-trihydroxyphenethylamine as a rapid method for laccase quantification. AB - The sensitivity of the autoxidation of 2,4,5-trihydroxyphenethylamine (6 hydroxydopamine) to increase by laccase was studied. The autoxidation of 6 hydroxydopamine proceeds by a free radical chain reaction involving O2- and produces the corresponding chromogen 6-hydroxydopaminequinone and hydrogen peroxide. The ability of laccase to increase the autoxidation of 6 hydroxydopamine at pH 5.5 has been used as sensitive assay for this enzyme. The results are tabulated and discussed. PMID- 8206742 TI - Regulation of dihydrodipicolinate synthase and diaminopimelate decarboxylase activity in Bacillus stearothermophilus. AB - The feedback inhibition of the enzymes dihydrodipicolinate (DHDPS) and diaminopimelate decarboxylase (DAPD) in the wild strain Zu 183 of Bacillus stearothermophilus and in its S-(2-aminoethyl)-cysteine resistant L-lysine overproducing strain AEC 12 was studied. The optimum temperature and pH of both enzymes were also evaluated. No inhibition of DHDPS by L-lysine, L-threonine, L methionine and L-isoleucine was observed either in the wild strain or in the AEC 12 mutant. DAPD was completely inhibited by L-lysine and only partially by L threonine and L-methionine in Zu 183 and AEC 12 strains, but the concentration required was found to be much higher in the AEC 12 strain. The regulation mechanism of L-lysine biosynthesis in Bacillus stearothermophilus Zu 183 was also discussed. PMID- 8206740 TI - Collagenase-extractable proteoglycans from lesion-free areas of human aorta. AB - Different proteoglycan (PG) populations were isolated from normal human aorta by extraction of minced tissue with 4M GuHCl and by further digestion of the residue with collagenase. Dissociative extraction induced a complete disappearance of Alcian Blue positive material, which was demonstrable by transmission electron microscopy before the treatment around collagen fibrils and in pericellular areas. However, 4M GuHCl extraction solubilized only an average of 60% of aorta total hexuronate content. Collagenase treatment of the residue resulted in a complete loss of collagen fibril organization, which was coupled with a further hexuronate recovery, accounting for about one third of total tissue content. The bulk of PGs obtained in collagenase digest was retained by Sepharose CL-4B column. Their sulphated glycosaminoglycan (GAG) composition differed from PGs extracted with 4M GuHCl, containing only chondroitin sulphate (CS) and heparan sulphate (HS), without detectable traces of dermatan sulphate (DS). Moreover, they contained hyaluronic acid. The results obtained by agarose polyacrylamide gel electrophoresis (APGE) and Octyl-Sepharose chromatography, followed by further APGE and Sepharose CL-4B gel-filtration, carried out before and after treatment with Chondroitinase ABC and AC and Heparinase I and III, suggested that collagenase digest contained different PG populations, carrying mainly either CS or HS chains. Moreover, HS containing PGs showed higher hydrodynamic size and stronger properties of hydrophobic interactions than CS containing PGs. PMID- 8206743 TI - Double cortex syndrome: electroclinical study of three cases. AB - We describe three female patients (aged 10, 11 and 21 years) with a Magnetic Resonance appearance of band heterotopia, a diffuse neuronal migration disorder, also known as double cortex syndrome. The clinical picture was characterized by the association of epilepsy and mental retardation in all three cases, as has been previously described in patients with double cortex syndrome. The epileptic syndrome (Lennox-Gastaut syndrome in one case, and symptomatic partial epilepsy in the other two), the response to medical treatment, and the severity of mental retardation were markedly different in the three patients. No clear-cut relationship was found between the clinical picture and the severity of the neuronal migration disorder, as revealed by magnetic resonance imaging. In the three cases, EEG shares some common features: multifocal epileptic activity with frequent bilateral diffusion, and high-amplitude anterior fast activity, intermingled in two patients with bursts of repetitive spikes. PMID- 8206744 TI - Evoked potentials in inherited ataxias: a multimodal electrophysiological study. AB - A multimodal electrophysiological study, including median nerve somatosensory evoked potentials (SSEPs), motor cortical stimulation (CS) and brainstem evoked potentials (BAEPs), was performed on 34 patients with hereditary ataxias (HAs): 15 with Friedreich's disease (FD), 10 with early onset cerebellar ataxia (EOCA), and 9 with autosomal dominant cerebellar ataxia (ADCA). A higher incidence of abnormal central motor conduction was observed in FD than in EOCA patients, but was never observed in ADCA. A relationship between central motor conduction abnormalities and disease duration and clinical impairment was found only in FD patients. All FD patients showed severe impairment of the SSEPs that was not related to disease duration. In EOCA patients, less frequent and more variable SSEP abnormalities were observed. The lowest incidence of central SSEP abnormalities was observed in ADCA. The BAEP findings in all 3 groups of patients (but particularly those with EOCA) suggest prevalent brainstem damage. PMID- 8206745 TI - Cerebral ischemia: magnetic resonance angiography and transcranial Doppler evaluation. AB - We examined 21 patients with ischemic cerebrovascular disease using magnetic resonance angiography and transcranial Doppler. In 17 patients (81%), the results obtained by the two methods were concordant. In our opinion, the associated use of transcranial Doppler and magnetic resonance angiography provides an accurate diagnostic evaluation of ischemic stroke patients, not only allowing the site of possible steno-occlusive disease of large and medium cerebral vessels to be identified, but also offering the possibility of obtaining dynamic information concerning the direction of blood flow in the presence of compensatory circulations at the level of Willis' circle. PMID- 8206746 TI - Homozygous hypertrophic hereditary motor and sensory neuropathies. AB - We compared 25 autosomal dominant hereditary motor and sensory neuropathy (HMSN) type I patients with 7 subjects affected by hypertrophic HMSN with non-dominant inheritance. All the autosomal dominant HMSN I cases carried the chromosome 17p11.2 duplication, providing evidence that it is widely represented in HMSN I families. The second group included: two siblings born to unrelated, unaffected parents and suffering from hypertrophic HMSN of strikingly different severity; two sisters with HMSN I phenotype, born to first-cousin unaffected parents; two brothers with HMSN III phenotype born to unrelated parents both showing HMSN II phenotype; a child with classic HMSN III phenotype, born to unrelated, unaffected parents. The 17p11.2 duplication was not found in any of the patients of the second series or in their parents. Our data provide further evidence that: HMSN III is heterogeneous and encompasses the homozygous expressions of different neuropathic genes; it is advisable to separate autosomal recessive hypertrophic HMSN from dominant HMSN Ia, because they appear to be due to different DNA mutations. PMID- 8206748 TI - Monosymptomatic presentation of type I Arnold-Chiari malformation: report of two cases. AB - Two cases of type I ACM are described, one of which presented with dizziness in late childhood (case 1), the other with mild intention tremor in adulthood (case 2). Cerebellar ectopia should be considered in monosymptomatic patients even in the absence of other symptoms and signs of C.N.S. dysfunction. Magnetic resonance imaging of the craniocervical junction should be performed because it may be diagnostic for type I ACM. PMID- 8206747 TI - Intravenous immunoglobulin, plasmalymphocytapheresis and azathioprine in chronic progressive multiple sclerosis. AB - Five patients with a severe form of chronic progressive multiple sclerosis no longer responsive to steroid therapy were treated for six months with high-dose intravenous immunoglobulin associated with plasmalymphocytapheresis and azathioprine. In spite of an apparent initial stabilization of the course of the disease, EDSS assessment after six and twelve months of therapy revealed progressive disability in all patients. PMID- 8206749 TI - Stroke as initial manifestation of relapsing polychondritis. AB - Relapsing polychondritis (RP) is a rare vasculitide characterized by recurrent inflammation of cartilagenous structures (auricular, nasal, laryngotracheal, articular) and specific sense organs (eyes and ear). Neurological complications are exceptional. We report the case of an elderly and previously well woman who presented with inflammatory syndrome and stroke as the first manifestations of this disease. PMID- 8206750 TI - Ceftriaxone is ineffective in ALS. PMID- 8206751 TI - Seed extract of Aeginetia indica L induces cytokine production and lymphocyte proliferation in vitro. AB - We previously reported that the extract of seeds from Aeginetia Indica L (AIL), a parasitic plant, induces potent antitumor immunity in tumor-bearing mice and that CD4+ T cells appear to be the main contributors in the induction of antitumor resistance. The present study was set up to investigate the in vitro effects of AIL on various lymphoid cells. Spleen cells from mice pretreated with AIL every 2 days for 1 week produced interleukin 2 (IL-2), interferon gamma (IFN gamma), tumor necrosis factor (TNF) and interleukin 6 (IL-6) when these cells were stimulated in vitro by AIL. Further, we found that CD4+ T cells were main producers of IL-2 and TNF upon the stimulation with ALL in vitro, while both CD4+ and CD8+ T cells secreted IFN. On the other hand, ALL was mitogenic in vitro to T enriched splenic lymphocytes as well as B enriched splenic lymphocytes. Moreover, AIL also proliferated thymocytes and this activity was potently synergistic with a suboptimal dose of concanavalin A (Con A). Lipopolysaccharide (LPS) contamination in AIL preparation was negligible since proliferative activity of AIL to B enriched splenic lymphocytes was not influenced in the presence of an endotoxin antagonist, polymyxin B sulfate (PMB). Further, B cell mitogenic activity of AIL seems to be mediated by different mechanism(s) from that of LPS since ALL could proliferate B enriched lymphocytes of C3H/HeJ mice which do not respond to the stimulation with LPS. A well known biological response modifier (BRM), Krestin (PSK), had no ability in inducing either T or B lymphocyte activation in vitro as shown by AIL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206752 TI - Augmented local immunity in the liver by a streptococcal preparation, OK432, related to antitumor activity of hepatic macrophages. AB - The aim of this study was to investigate the augmentative effect of a streptococcal preparation, OK432, on the immunological competence of hepatic macrophages. We found that OK432 was distributed predominantly to hepatic macrophages after intravenous injection, and Northern blot analysis revealed that OK432 induced the gene expression of IL-1 alpha, beta, and TNF alpha in the liver. The induction of mRNAs was evident 1 h after the intravenous injection of OK432 and their accumulation reached a maximal level at 3 h. TNF production of hepatic macrophages was also increased by the intravenous injection of OK432. Furthermore, OK432 significantly increased the proportion of IL-2 receptor positive hepatic macrophages. As for antitumor activity in the liver being augmented by OK432, the cytotoxic and cytostatic activity of hepatic macrophages from OK432-treated rats against tumor cells was significantly increased and OK432 markedly reduced the number of tumor nodules in the liver after the inoculation of tumor cells via the portal vein. These findings, which indicate that OK432 has various immuno-stimulating actions on hepatic macrophages, leading to the augmentation of antitumor activity in the liver, suggest that OK432 may be of some benefit in helping to prevent hepatic metastasis, at least in part, via its activation of hepatic macrophages. PMID- 8206754 TI - Effects of aflatoxin B1 and T-2 toxin on the granulocyte-macrophage progenitor cells in mouse bone marrow cultures. AB - Myelotoxic effects of aflatoxin B1 (AFB1) and T-2 toxin on the proliferation of the granulocyte-macrophage progenitor cells to granulocyte, macrophage and granulocyte-macrophage (GM) colonies were investigated in male CD-1 mice by a semisolid in vitro culture technique. Mice received 0, 0.03, 0.145 and 0.7 mg/kg or 0, 0.1, 0.5, and 2.5 mg/kg body weight of AFB1 and T-2 toxin, respectively, for 2 weeks on alternate days. Granulocyte, macrophage, and GM-colonies were suppressed in the group that received the highest dose of AFB1 (0.7 mg/kg body weight). Treatment with T-2 toxin activated granulocyte colonies at 0.5 mg/kg and macrophage colonies at 0.1 and 2.5 mg/kg but suppressed GM-colonies at 0.5 and 2.5 mg/kg body weight. Bone marrow cells from normal CD-1 mice were cultured with different concentrations of AFB1 (1-50 microM) or T-2 toxin (1-10 nM) in vitro. Significant activation of granulocyte colonies with 1 microM AFB1 and suppression of all three types of colonies with the highest concentration of AFB1 (50 microM) were observed. The suppression of granulocyte and GM-colonies associated with T-2 toxin was concentration-dependent. The greatest suppression occurred in macrophage colonies with three highest concentrations of T-2 toxin (3, 6, and 10 nM). Results suggest that AFB1 is myelotoxic both in vivo and in vitro, whereas T 2 toxin is more toxic in vitro. PMID- 8206753 TI - Glucocorticoid-mediated inhibition of interleukin-2 receptor alpha and -beta subunit expression by human T cells. AB - To determine the mechanism of glucocorticoid (GC)-mediated inhibition of T cell functions, the effect of dexamethasone (DM) on T cell proliferation and interleukin-2 receptor (IL-2R) generation were studied. Dexamethasone inhibited IL-2-induced T cell proliferation by 30%-88%, relative to its concentration within the cultures. The effect of DM on expression of IL-2R alpha (Tac, p55, CD25) and beta (p75) genes in activated T cells was examined next. In T cells stimulated with purified phytohemagglutinin (PHA-p) and 4 beta-phorbol 12 myristate 13-acetate (PMA) addition of DM to the cultures resulted in a 60% reduction in IL-2R alpha and a 30% reduction in IL-2R beta membrane expression compared to T cells cultured in the absence of DM (p < 0.01). Inhibition of membrane IL-2R alpha and IL-2R beta expression by 10(-6) M DM was partially reversible by recombinant human IL-2 (rhIL-2). By Northern blot analysis, DM caused a comparable decrease in IL-2R alpha and in IL-2R beta mRNA levels to membrane receptor expression in mitogen-stimulated T cells. By in vitro transcription assays, DM regulated IL-2R alpha gene expression at a transcriptional level while transcription of IL-2R beta gene was unaffected by DM. The mechanism of action of DM on IL-2R alpha transcription was examined by determining the mRNA levels of the p50 subunit of nuclear factor kappa B (NF kappa B), a transcription factor that stimulates IL-2R alpha gene expression. The data indicate that 10(-6) M DM increased T cell p50 NF-kappa B mRNA levels by four-fold compared to the levels obtained in the absence of DM. Further, the level of nuclear proteins capable of binding to the NF-kappa B sites in activated T cells increased in response to DM. In sum, DM regulates T cell membrane expression of IL-2R by more than one molecular mechanism. PMID- 8206755 TI - Inhibition of IFN-gamma induction of class II MHC genes by cAMP and prostaglandins. AB - Triggering of the cyclic AMP (cAMP) signal transduction pathway inhibits the the interferon gamma (IFN-gamma)-mediated induction of class II major histocompatibility (MHC) genes. We have investigated the mechanism of the inhibition of IFN-gamma induction of the murine A alpha class II MHC gene by cAMP and E series prostaglandins (PGEs). 151 base pairs of the A alpha promoter were sufficient to confer positive regulation by IFN-gamma and negative regulation by cAMP which accurately mirrored the regulation of the endogenous A alpha gene. cAMP also inhibited the IFN-gamma activation of the Fc gamma receptor I (Fc gamma RI) gene promoter, an "early" promoter which is activated immediately after treatment of cells with IFN-gamma. PGEs, which cause an elevation in intracellular cAMP, inhibited the induction of the A alpha promoter, and inhibition was greater in the presence of tumor necrosis factor alpha (TNF alpha). A mutational analysis of the A alpha promoter showed that all four conserved class II promoter elements, the S, X1, X2, and Y boxes, play a role in mediating A alpha promoter activation by IFN-gamma. Mutations in these elements did not diminish the cAMP inhibition of promoter activation by IFN-gamma. Thus, conserved class II promoter sequences which mediate most known examples of positive and negative regulation, including cAMP inhibition of constitutive class II expression, do not mediate cAMP inhibition of IFN-gamma activation of the A alpha promoter. We suggest that this inhibition may be mediated by a novel class II promoter element or by disruption of an early step in the IFN-gamma signal transduction pathway. PMID- 8206756 TI - A potential vaccine for cocaine abuse prophylaxis? AB - O. Bagasra, L.J. Forman, A. Howeedy, and P.A. Whittle recently conveyed the preparation of a cocaine immunogen that is a potential vaccine for cocaine abuse prophylaxis (Immunopharmacology: 1992, 23, 173-179). These investigators claim to have prepared a cocaine immunogen via reaction of cocaine with sodium metaperiodate followed by carrier protein, and to have generated anti-cocaine antibodies by using this immunogen. Periodate is used to conjugate haptens that contain a vicinal diol (or similar) group to carrier proteins and would not be expected to couple cocaine to protein. The authors of the above publication reported titres for antibodies generated by using their immunogen, but did not describe competitive inhibition of antibody binding by cocaine and did not report the specificity characteristics of their antibodies. The present author is not convinced by the claims made by Bagasra et al. PMID- 8206757 TI - Financial and clinical performance: bridging the gap. AB - The article explores the relationship between the cost and the quality of hospital care by elaborating a conceptual model of hospital performance. The model relates the financial health status of an organization (financial integrity) to the quality of care provided by that organization (clinical integrity) within an environment that is characterized by various forms of risk. The model suggests that both concepts determine the corporate destiny (success, bankruptcy, or merger) of the organization. If this model proves valid empirically, the results could be used as an early warning system to identify hospitals that might experience financial or clinical distress. PMID- 8206758 TI - Union election activity in the health care industry. AB - The health care industry in the United States has undergone many changes in recent years. One problem facing employers in this industry is the threat of unionization. The article examines union election activity since 1980 in hospitals, nursing homes, and other types of health care employers. Variance in the union victory rate was found over time and across the different sectors of the industry, types of employees involved, union involved, and sizes of the bargaining unit. The effects of geographic location and type of ownership are investigated. Decertification elections are also examined. PMID- 8206759 TI - Measuring gain-sharing dividends in acute care hospitals. AB - Hospitals have responded to industry consolidation by increasing productivity with nonmanagement, group-incentive compensation, known as gain sharing. A nationwide study conducted to obtain quantitative performance data for gain sharing programs revealed that they are most successful during the initial stages of the program. Many variables affect the size of employee bonuses and the duration of employee support. Employers must identify how to appropriately install their gain-sharing program so that employee motivation, participation, and trust in management are maximized. PMID- 8206760 TI - Hospital markets and competition: implications for antitrust policy. AB - Antitrust and competitive issues are intertwined with efforts to control health care costs. Whether hospital competition holds down costs is an issue of much controversy and is the topic of this article. The findings are consistent with the hypothesis that hospitals compete primarily on a nonprice basis. This suggests that a more flexible application of antitrust policy to hospital mergers will reduce cost increases and will improve efficiency. A step in this direction may be necessary if the managed care plans discussed by the Clinton administration create highly concentrated provider networks. PMID- 8206761 TI - An examination of winners and losers under Medicare's prospective payment system. AB - Through case studies of 10 matched pairs of winner and loser hospitals under the Medicare prospective payment system (PPS), specific characteristics and management actions were identified that are related to strong financial performance. Because other payers are increasingly adopting PPS-like cost control incentives and because managed care is fundamental to the national health care reform debate, the successful strategies identified in this article may be of increasing importance to hospital managers. PMID- 8206762 TI - Hospital cost incentives in a fragmented health care system. AB - During the mid-1980s, hospital prospective payment regulation was associated with major changes in medical practice, resulting in initially significant reductions in the rate of growth of inpatient costs. More recently, the rate of growth of hospital costs has returned to historic levels, yet most hospitals have been reluctant to intensify their economic monitoring of physicians. Using data from a large teaching hospital in the Midwest, this article presents a model of marginal profitability by payor and by relative physician costliness. The results illustrate the mixed incentives for hospitals to reduce costly medical practice variations. PMID- 8206763 TI - Bond ratings, debt insurance, and hospital operating performance. AB - In this study, the operating performances of not-for-profit community hospitals are compared among groups partitioned by bond ratings, level of debt insurance coverage, and number of bond rating services. The analysis indicates that the performances of hospitals with full debt insurance coverage resulting in AAA ratings are significantly lower than those of hospitals with partial debt insurance and with AA ratings or better. Indeed, the hospitals with full debt insurance resemble those with partial insurance that are rated BBB to A. These findings have implications for managerial action choices. Hospitals seeking external funding to improve their operating performance may consider the costs and benefits of full insurance coverage. PMID- 8206764 TI - Reassessing the codependency movement: a response to Sorrentino. AB - The literature on codependency has had a profound effect upon drug abuse counselors and the clients they serve. Originally derived from the alcoholism treatment field, the codependency concept is increasingly noted in the health care administration literature. Interventions such as employee assessment and counseling programs have been suggested by Sorrentino and others as ways to prevent the negative outcomes of codependent behavior among employees in health care organizations. A reassessment of the literature over the last decade, however, does not support the codependency concept or the treatment formats. Recommendations for health services administrators are subsequently offered. PMID- 8206765 TI - HCMR perspective: collaboration, competition, and communication--a field experience on the road to reform. PMID- 8206766 TI - Coping in spouses of patients with acute myocardial infarction in Taiwan. AB - OBJECTIVE: The purpose of this study was to determine the usage and perceived effectiveness of coping strategies of spouses of patients with acute myocardial infarction in Taiwan, the Republic of China, during the acute phase of the illness. DESIGN: Survey. SETTING: Visitors room for a coronary care unit in Taiwan, the Republic of China. SUBJECTS: Twenty-one female and 10 male spouses of patients with acute myocardial infarction. OUTCOME MEASURES: The Revised Ways of Coping Scale was modified to assess both frequency of use and perceived effectiveness of coping strategies. It was also translated into Chinese. RESULTS: Seeking Social Support was the most frequently used coping strategy, whereas Confrontive Coping was used the least. There were significant positive relationships between the extent of usage of coping strategies and their perceived effectiveness. Men used Planful Problem-Solving more often and found it be more effective than did women; they also found the Self-Controlling and Accepting Responsibility strategies to be more effective than did women. Older spouses reported the Planful Problem-Solving strategy to be more effective than did younger subjects. The more family members living with a spouse, the less Accepting Responsibility was used as a coping strategy. CONCLUSIONS: Spouses of patients with acute myocardial infarction in Taiwan, the Republic of China, report using a variety of coping strategies. Those used most often are perceived to be the most effective. PMID- 8206767 TI - The effect of early ambulation on patient comfort and delayed bleeding after cardiac angiogram: a pilot study. AB - OBJECTIVE: To examine the effects of ambulation at 3 versus 6 hours on delayed bleeding, pain, and anxiety in patients after cardiac angiogram. DESIGN: Experimental, pretest posttest, random assignment. SETTING: Western Canadian University-affiliated tertiary care hospital. PATIENTS: Thirty-nine patients who underwent cardiac angiograms. OUTCOME MEASURES: Delayed bleeding, pain, and anxiety. INTERVENTION: The experimental group ambulated at 3 hours after cardiac angiogram; the control group ambulated at 6 hours. Delayed bleeding was evaluated by sanguinous drainage through a standard gauze pressure dressing and/or the presence of a palpable hematoma greater than 5 cm in width. Melzack's Present Pain Intensity Scale and Spielberger's State Anxiety Inventory were used to evaluate patient comfort at 2, 4, and 7 hours after angiogram and the next day. RESULTS: None of the patients experienced any delayed bleeding. Student's t test was used to compare pain levels and anxiety scores. In addition, repeated measures analysis of variance was applied to pain scores taken at 4 hours, 7 hours, and the next day. The 2-hour observation data were used as a covariate and a basis for comparison of pain at the next three observations. Patients ambulating early had significantly less pain overall (p < 0.005) and less back pain at 4 and 7 hours after angiogram (p < 0.05). There was no significant difference in the mean anxiety scores. CONCLUSION: The significant decrease in back pain of patients who ambulated earlier demonstrates the need to consider patient comfort as well as the potential risks and sequelae of delayed bleeding. PMID- 8206768 TI - Hyperinsulinemia and cardiovascular risk. AB - Tissue insulin resistance and compensatory hyperinsulinemia cause early atherosclerosis and an increased cardiovascular risk for the non-insulin dependent diabetic individual. Evidence now indicates that a large and likely unrecognized number of individuals are insulin resistant and hyperinsulinemic and therefore share this risk. Ongoing investigation of this phenomenon may produce changes in the methods for earlier identification of these individuals and in the treatment of obesity, diabetes, and cardiovascular disease and may expand the areas in which nursing intervention can alter outcome. PMID- 8206769 TI - Hemothorax and an abdominal hematoma after treatment of ischemic cardiomyopathy with warfarin. PMID- 8206770 TI - A trial of lidocaine. PMID- 8206771 TI - Preparing adult patients for cardiac catheterization: informational treatment and coping style interactions. AB - OBJECTIVE: To examine the interacting effects of coping style and type of preparatory informational treatment on cardiac catheterization patient anxiety. DESIGN: Pretest-posttest randomized control group design. SETTING: Canadian, university-affiliated, large urban hospital. SUBJECTS: 145 adult patients (107 men and 38 women) scheduled for their first cardiac catheterization. Age range was from 34 to 78 years. Mean educational level was 10.72 years. OUTCOME MEASURES: Subject's coping style (monitoring [information seeking] or blunting [information avoiding]) was assessed by means of Miller's Behavioral Style Scale. Subject's anxiety was assessed by means of Speilberger's A-Trait and A-State Inventory. INTERVENTION: After coping style assessment, monitors and blunters were randomly assigned to receive one of three preparatory informational treatments: (1) videotaped procedural modeling information; (2) videotaped procedural-sensory modeling information; and (3) procedural-sensory information booklet. RESULTS: Subjects' anxiety was assessed before and after intervention (Time 1 and Time 2) and before and after catheterization (Time 3 and Time 4). Analysis of variance techniques applied to the anxiety data largely confirmed the hypothesized interaction between subjects' coping style and type of preparatory informational treatment. Monitors who received the procedural-sensory modeling video treatment and blunters who received the procedural modeling video treatment reported significant reductions in A-state anxiety at Time 2 and maintained that decrease at Time 3. In contrast, monitors and blunters who received the other preparatory informational treatments reported a significant increase in A-state anxiety or a nonsignificant change in A-state anxiety at Time 2 and Time 3. At Time 4 monitors and blunters in each of the treatment groups reported a significant decrease in A-state anxiety. CONCLUSIONS: Two unexpected findings emerged from the study: (1) female monitors and blunters reported significantly higher A-state anxiety levels than their male counter-parts at preintervention, and (2) significant differences were observed among the preintervention A-state anxiety means of male monitors in the three preparatory treatment groups. These findings limit the conclusions that can be drawn from the study but provide direction for future research in the preparatory area. PMID- 8206773 TI - A nurse-delivered smoking cessation intervention among hospitalized postoperative patients--influence of a smoking-related diagnosis: a pilot study. AB - OBJECTIVE: To examine the effect of a nurse-delivered smoking cessation intervention on short-term smoking abstinence among hospitalized postoperative patients. DESIGN: Prospective, experimental, random assignment. SETTING: Midwestern university-affiliated tertiary medical center. PATIENTS: Postoperative smokers (n = 80) from cardiovascular, oncology, and general surgical units. OUTCOME MEASURE: Self-reported smoking status and saliva cotinine level at 5 to 6 weeks after hospitalization. INTERVENTION: Three structured smoking cessation sessions during hospitalization, followed by phone calls once a week for 5 weeks after discharge. RESULTS: Of the experimental group patients, 37.8% were abstinent as compared to 25.6% in the usual care group. Abstinence rates of experimental group patients from cardiovascular (40%) and oncology (64.3%) units were higher than that of GS (13.3%) unit patients. Regardless of group assignment, 100% of cardiovascular and oncology patients abstained during hospitalization, compared to only 10.7% of GS patients. CONCLUSIONS: Preliminary results indicate that a nurse-delivered cessation intervention may be effective postoperatively among smokers with an identified smoking-related diagnosis. PMID- 8206772 TI - Undergoing cardiac catheterization: the effects of informational preparation and coping style on patient anxiety during the procedure. AB - OBJECTIVE: To examine the effects of coping styles and preparatory informational treatments on patient anxiety during cardiac catheterization. DESIGN: Prospective, experimental, random assignment, repeated measures design. SETTING: Canadian, university-affiliated, large urban hospital. SUBJECTS: 145 adult patients (107 men and 38 women) scheduled for their first cardiac catheterization. Age range was from 34 to 78 years. Mean educational level was 10.72 years. OUTCOME MEASURES: Subject's coping style, "monitoring" (information seeking) or "blunting" (information avoiding) was assessed by means of Miller's Behavioral Style Scale. Subjects' anxiety was assessed using three measures: (1) a self-report measure, the Subjective Units of Distress (SUDS) Scale; (2) a behavioral measure, the Cardiac Catheterization Adjustment (CA) Scale; and (3) physiologic measures, heart rate and systolic and diastolic blood pressure. INTERVENTION: After coping style assessment, monitors and blunters were randomly assigned to receive one of three preparatory informational treatments: (1) videotaped procedural modeling information, (2) videotaped procedural-sensory modeling information, and (3) procedural-sensory information booklet. RESULTS: Analysis of variance techniques applied to the anxiety data revealed the following: (1) significant changes in self-reported patient anxiety occurred as a function of occasion rather than preparatory informational treatment or coping style, (2) subjects receiving the three preparatory informational treatments demonstrated significantly different behavioral adjustments during cardiac catheterization, and (3) most subjects demonstrated heart rate and blood pressure readings in the normal range; however, significant changes in cardiovascular reactivity were found to be associated with contrast dye insertion. CONCLUSIONS: Subjects who received the videotaped modeling treatments demonstrated greater behavioral adjustment than patients who received the information booklet. Questions remain as to whether the procedural modeling treatment is more efficacious than the procedural-sensory modeling treatment. Increases in subjects' SUDS levels were found to be associated with changes in ideational content. Changes in blood pressure and heart rate were attributed to physiologic and psychologic factors. Coping style did not appear to significantly influence any of the measures of patient anxiety. PMID- 8206774 TI - Caregiver learning needs and reactions to managing home mechanical ventilation. AB - OBJECTIVE: To identify caregivers' learning needs and reactions to providing care for adult patients receiving mechanical ventilation in the home. This report originated from a study that was undertaken to describe family function and reactions of family members. DESIGN: Prospective, descriptive. SETTING: Data collected at clients' homes in a midwestern city. SUBJECTS: Twenty caregivers and adult patients who are dependent on mechanical ventilation at home. INSTRUMENTS: Patients and their caregivers completed family coping and family function instruments. Caregivers also completed a Learning Needs Checklist and a caregiving inventory. RESULTS: The results indicate that caregivers, all relatives, provided an average of 7.3 hours per day direct care with little assistance from extended family or professionals. More disrupted schedules, financial strain, increased burden, and negative reaction to caregiving was associated with increasing ventilator hours per day. Family function was perceived as satisfactory by both patients and caregivers. Survival knowledge and skills were being taught, but additional information was needed by caregivers. There were no differences by gender in perceived learning needs, family function, or tasks of daily caregiving. CONCLUSIONS: Preferences for types of information suggest the use of a three-phase teaching program that should be sensitive to individual learning needs. A variety of coping strategies were used by families to manage home mechanical ventilation including problem-solving and mobilizing help from friends, extended family, community, or church. PMID- 8206775 TI - Infant botulism. AB - Constipation in children is rarely thought of as a serious health condition. It is, however, one of the leading symptoms of the pathologic sequence in infantile botulism. The pathogenesis, common clinical manifestations, and common grounds in treatment and prognosis in infant botulism are summarized. The nursing role is presented, focusing on airway management, nutritional needs, environmental support, and parental role in an intensive care unit. An exemplar case study is presented. PMID- 8206776 TI - The use of analgesics and sedatives in critically ill patients: physicians' orders versus medications administered. AB - OBJECTIVE: To examine the difference between the prescribed and actually administered dose of analgesic and sedative drugs in critically ill patients. DESIGN: Prospective survey. SETTING: University hospital surgical intensive care unit. SUBJECTS: One hundred fifty consecutive adult patients admitted to a surgical intensive care unit over a 3-month period. METHODS: Data were gathered on a daily basis. The sedation and analgesia given were compared with the daily physician orders. RESULTS: Narcotics and benzodiazepines were most commonly used. On average only 22% to 52% of the mean ordered dose of intravenous and intramuscular morphine was actually administered. Larger doses of morphine were administered to intubated patients than to nonintubated ones. Patients receiving intravenous fentanyl infusions generally were administered more than the ordered dose. The actual and prescribed doses of epidural fentanyl were well matched. Midazolam was the most frequently prescribed benzodiazepine. Like morphine, the amount administered was below the maximum ordered by the physicians. CONCLUSIONS: Physicians tended to write fairly nonspecific orders that were used by the nursing staff as very broad guidelines. A need exists to educate physicians as to what patients actually receive for sedation and analgesia and at the same time improve the dialogue between nurses and physicians as to what patients actually require. PMID- 8206777 TI - Listeria monocytogenes meningoencephalitis: the diagnostic importance of the CSF lactic acid. PMID- 8206778 TI - Cardiac retransplantation: determining limits. PMID- 8206779 TI - Comparison of two methods of measuring gastric pH. PMID- 8206780 TI - Preserving the self: women having cardiac surgery. AB - OBJECTIVE: To explore the process that women undergo when having cardiac surgery. DESIGN: A grounded theory approach was used to gain an understanding of the core process. SETTING: A large community hospital with an active cardiovascular surgery practice and research center. PARTICIPANTS: Ten women, between 21 and 79 years of age, who had undergone cardiac surgery in the last 3 months. RESULTS: Behaviors in which the women were engaged when having cardiac surgery were directed toward "preserving the self" while getting through the surgical experience. This process had five phases: waiting, getting there, surviving, being there, and moving on. Strategies used by these women in preserving the self throughout the phases were: relating, making sense of, managing, and normalizing what was happening to them. CONCLUSION: By having a clearer understanding of the process women undergo when having cardiac surgery, health care providers will be able to participate more effectively with women through their experience. PMID- 8206781 TI - The C-, G-, and R-banded karyotype of the scimitar-horned oryx (Oryx dammah). AB - Karyotypes of five males and one female scimitar-horned oryx (Oryx dammah) were prepared using lymphocyte and skin cells. CBG-, GTG-, and RBG-banded chromosomes were analysed and the banding patterns were compared with those of cattle, revealing a high level of homoeology except for chromosomes 9, 14, 21, Y, and X. Standard karyotypes are proposed for the scimitar-horned oryx karyotype, which contains 58 chromosomes with one pair of large submetacentric autosomes and 27 acrocentric autosomal pairs. The X and Y chromosomes are the largest and smallest acrocentrics. The scimitar-horned oryx chromosome 1 is submetacentric and appears to result from the fusion between ancestral forms of bovid chromosomes numbered 1 and 29 according to the READING CONFERENCE (1980) nomenclature and to ISCNDA 89 if GTG-banding is used. PMID- 8206782 TI - Mapping of the interferon gamma (IFNG) gene in river and swamp buffaloes by in situ hybridization. AB - In situ hybridization technique was applied using a tritiated (3H) bovine IFNG cDNA probe to regionally localize the gene on river and swamp buffalo chromosomes. The hybridization signals peaked on the 4q23-->q26 bands in river buffaloes and on the 1p24-->p26 bands in swamp buffaloes. The results are compared to the localization of the same gene in cattle. Possible evolutionary conservation in the Bovidae is discussed. PMID- 8206783 TI - Spontaneous chromosome aberrations in Fanconi's anemia patients are located at fragile sites and acute myeloid leukemia breakpoints. AB - Spontaneous chromosome aberrations (CA) were analyzed in 3 Fanconi's anemia (FA) patients, 8 family members, and 9 healthy individuals. Peripheral blood lymphocytes obtained from each individual were cultured and cytogenetic analysis was performed on standard and sequential G-banded metaphases. The numbers of abnormal cells and breaks were found to be higher in AF patients compared to the other groups (p < 0.0001). Breakpoint distribution was statistically analyzed considering the formula proposed by Brogger (1977), showing a non-random pattern among FA patients but not among controls or relatives (p < 0.001). Five chromosomal bands located at 1p36, 1p22, 1q21, 3p14, and 3q21 were non-randomly involved in spontaneous CA in FA patients. These bands were correlated with the chromosomal location of fragile sites, oncogenes, and breakpoints involved in cancer-rearrangements. A significant correlation with the location of fragile sites (p < 0.03) and breakpoints involved in cancer-rearrangements (p < 0.001), particularly with AML chromosome anomalies (p < 0.03) was found, suggesting a possible relationship with the high predisposition to cancer observed in this disease. PMID- 8206784 TI - The influence of vinblastine treatment on the formation of radiation-induced micronuclei in mouse bone marrow. AB - The combined effects of vinblastine sulphate (VBL) and gamma radiation treatments on the induction of micronuclei in polychromatic erythrocytes (MPCE) and normochromatic erythrocytes (MNCE) and changes in polychromatic/normochromatic erythrocyte ratio (P/N ratio) in mouse bone marrow, were studied. Compared to double distilled water (DDW) injected controls, 0.05 mg/kg b.wt. of vinblastine alone significantly increased the frequency of MPCE and MNCE. When VBL was administered before exposure to various doses of gamma radiation the frequency of micronuclei (MPCE and MNCE) increased with the increasing radiation dose up to a dose of 4 Gy, but this increase levelled off at 3 to 4 Gy irradiation. The frequency of MPCE was found to be significantly lower at 3 and 4 Gy radiation when compared to the DDW+irradiated group. A significant dose dependent decline in the P/N ratio was observed in the DDW+irradiated group. VBL treatment before irradiation resulted in a more significant decline in the P/N ratio than that of DDW+irradiated group. The formation of micronuclei (MPCE and MNCE) increased from 8 h post-exposure and continued to increase up to 28 h. There was a sharp decline in the frequency of micronuclei (MPCE and MNCE) at 32 h post-irradiation, in both DDW + 1 Gy irradiated and VBL + 1 Gy irradiated groups; then it declined gradually up to 72 h post-exposure without restoration to normal level. The P/N ratio declined with time in all three groups (VBL alone, DDW+irradiation, and VBL+irradiation) without restoration to normal level up to 72 h post-treatment, except in the DDW+irradiated group, where it was normal. PMID- 8206785 TI - The human language faculty: genetically determined? An approach to testable hypotheses. AB - A kind of generation gap seems to divide researchers interested in the evolutionary status of the human language capacity. There is still opposition to the theory of a genetically determined universal or primal grammar. But although not well acquainted with the transformational-generative linguistic methodology that led to the hypothesis, an increasing number of linguists base their work with a "new grammar" on the acceptance of innateness of the human language faculty. It is proposed that dyslexia offers a hypothesis testable with the new advanced gene mapping, and that Creole Languages and Sign Languages of the Deaf may come to offer possibilities of similarly testable hypotheses. PMID- 8206786 TI - Sperm chromosome study of two bulls heterozygous for different Robertsonian translocations. AB - Haploid chromosomes of a total of 354 spermatozoa from two bulls heterozygous for different Robertsonian translocations, a Holstein-Friesian bull carrying a t(1;21) and a Japanese Black bull carrying a t(7;21), were analyzed using an interspecific in vitro fertilization system with zona-free hamster oocytes. The proportion of chromosomally normal and balanced spermatozoa was approximately equal in both carriers (51.8% and 47.0% in the 1/21 carrier, and 47.3% and 50.0% in the 7/21 carrier). The combined incidences of normal and balanced spermatozoa, i.e., incidences of spermatozoa resulting from alternate meiotic segregation were very high (98.8% and 97.3%) in both carrier. On the contrary, the incidences of chromosomally unbalanced spermatozoa resulting from adjacent meiotic segregation were only 0.6% and 2.7%. These results indicate that the alternate segregation of a trivalent chromosome is predominant in these Robertsonian translocation carriers. PMID- 8206787 TI - The male pseudohermaphrodite XX polled goat is Zfy and Sry negative. AB - The Polled mutation of the goat is inherited as an autosomal dominant trait. Homozygotes with a 60,XX karyotype develop into intersexes. We looked for the presence of Y-chromosomal sequences (Zfy and Sry) in a male pseudohermaphrodite polled goat by Southern blotting and PCR analysis. Molecular analysis revealed that this XX goat had no Sry sequence. It showed identical hybridization patterns, using the human SRY and ZFY probes at low stringency, with the normal XX female goat, whereas an XY male revealed prominent Sry and Zfy signals. Identical results were obtained from PCR analysis with the caprine Sry primers. The possible role of an autosomal recessive gene in the induction of testes and maleness is discussed. PMID- 8206788 TI - NADPH-dependent lipid peroxidation capacity in unfixed tissue sections: characterization of the pro-oxidizing conditions and optimization of the histochemical detection. AB - Factors which influence the iron-stimulated lipid peroxidation in rat liver have been studied by incubating unfixed cryostat sections with a pro-oxidant system and using an optimized histochemical detection method for lipid peroxidation products with 3-hydroxy-2-naphthoic acid hydrazide and Fast Blue B. We used a method that was slightly different from the one described previously. The final reaction product was exclusively localized in the cytoplasm of liver parenchymal cells with a homogeneous distribution within the liver lobule. The absorbance maximum, as measured cytophotometrically, was found to be 550 nm. Maximum lipid peroxidation was observed when the pro-oxidant system contained 0.2 mM NADPH, 1 mM ADP and 15 microM FeCl2. Some reaction product was found when NADPH was omitted. Iron concentrations higher than 180 microM prevented the formation of lipid peroxidation products in certain areas of the sections, whereas ADP concentrations higher than 1 mM inhibited the reaction in the whole section. A pH dependency was also observed, with the highest lipid peroxidation at pH 7.2. Optimum lipid peroxidation was induced by incubating for 30 min at 37 degrees C with the pro-oxidant system. A linear relationship was found between the thickness of the sections (up to 20 microns) and the amount of lipid peroxidation products. The addition of scavengers of O2-. (superoxide dismutase), hydrogen peroxide (catalase) and OH. (mannitol) to the first step medium did not affect the amount of final reaction product. These findings appear to confirm the hypothesis proposed for events occurring in isolated microsomes, leading to the formation of hydroperoxides and ultimately lipid peroxidation-derived carbonyls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206789 TI - Lectins as markers of rumen epithelial cell differentiation. AB - Lectins of different carbohydrate specificities (GNA (Galanthus nivalis), con A (Canavalia ensiformis), VFL (Vicia faba), PSL (Pisum sativum), LCA (Lens culinaris), PNA (Arachis hypogaea; with or without prior neuraminidase treatment), WGA (Triticum vulgare), SBA (Glycine max), UEA-I (Ulex europaeus), LPA (Limulus polyphemus), BS-I B4 (Bandeiraea simplicifolia, isolectin B4)) were explored for use as differentiation markers of rumen epithelial cells in vivo and in vitro. Lectins specific for mannose (GNA), mannose/glucose (con A, VFL, PSL and LCA), N-acetylglucosamine (WGA) or for N-acetylneuraminic acid (LPA) reacted generally with all types of rumen epithelial cell from both rumen tissue and cell culture. They were, therefore, not suitable markers of epithelial differentiation. SBA was unsuitable because, although it reacted with both tissue and cultured rumen epithelial cells, it was also bound to non-stratified areas of primary rumen epithelial cell cultures. Both BS-I B4 and PNA (after neuraminidase treatment) had to be ruled out because they did not react with differentiated rumen tissue epithelial cells, although they did bind to both stratified and non stratified cultured cells. In contrast, UEA-I reacted strongly with differentiated rumen epithelial cells both from rumen tissue and cell cultures and therefore appears to be a good general marker for rumen epithelial cell differentiation. PMID- 8206790 TI - Regional differences in glucose transport in the mouse hippocampus. AB - In order to observe glucose transport into the brain, 6-[N-(7-nitrobenz-2-oxa-1,3 diazol-4-yl)amino]-6-deoxyglucose (NBDG), a non-metabolizable and fluorescent glucose analogue, was injected intravenously into mice. After ascertaining that this glucose analogue is non-metabolizable in the brain, the NBDG contents in the blood and brain were measured quantitatively by spectrofluorimetry at 0, 0.5, 2, 5, 10 and 30 min after intravenous injection. The NBDG content in the blood decreased markedly with time, whereas in the brain it rapidly decreased, then gradually increased after 2 min. Glucose transport into the hippocampus was observed with a confocal laser scanning microscope. At 0.5 min, NBGD was seen to be highly concentrated on the vascular wall. Using the confocal mode, it was found that the fluorescence was unevenly distributed on the microvessel wall, suggesting local differences of glucose transport in the vascular wall. At 5 min, the fluoresent intensity of the vascular wall was markedly decreased, whereas relatively intense fluorescence was observed in the cerebral parenchyma of the stratum lacunosum-moleculare and stratum pyramidale of Ca3. At 10 min, a weak fluoresence was diffusely distributed in the hippocampus. As to the localization of NBDG in the brain, capillary endothelium (luminal and abluminal membrane), basement membrane, and the feet of the astrocytes are discussed. PMID- 8206792 TI - Reflections on a psychoanalytic theory of gender difference. PMID- 8206791 TI - Comparative enzyme histochemistry of the early and term rat decidua with special attention to decidual regression. AB - As the early rat decidua is believed to fulfil functions other than the late or basal decidua, the question as to whether this difference is reflected in decidual cell metabolism was investigated. Using cryosections of pregnant rat uteri of the 10th, 15th and 21st gestational day, activities of oxyradical forming enzymes and hydrolases were analysed histochemically. The enzyme activities of decidual stromal cells and fibroblasts of the metrial gland exhibited three main fluctuations. One group of enzyme activities did not change during gestation, a second group decreased or disappeared, and a third group increased or was expressed in the late decidua only. Enzymes of the purine and polyamine pathway, including oxyradical-forming oxidases, were absent from early mesometrial decidual cells, but were highly active in the late regressing decidua and metrial gland. Some acid hydrolases and neutral proteases became active in the mature decidua. The possibility that purine-degrading and oxyradical-forming enzymes support decidual as well as metrial gland regression, and thus placental separation, by direct tissue damage and/or by indirect rupture of lysosomal membranes, inducing the release of acid hydrolases, is considered. PMID- 8206793 TI - Malignant transference: a neurobiologic model. PMID- 8206794 TI - Fear of success: psychodynamic implications. PMID- 8206795 TI - Freud's analysis of Horace Frink, M.D.: a previously unexplained therapeutic disaster. PMID- 8206796 TI - Little girls who become angels: the prohibition of feminine narcissism in the children's stories of Hans Christian Andersen. PMID- 8206797 TI - Mind, brain, and machine: action and creation. PMID- 8206798 TI - On rereading the case of Anna O.: more about questions that are unanswerable. PMID- 8206799 TI - Edvard Munch: a life in art. PMID- 8206800 TI - Bilateral electrodermal activity and cerebral mechanisms in syndromes of schizophrenia and the schizotypal personality. AB - Bilateral electrodermal measurement was among the first to investigate abnormalities of lateralization in schizophrenia, and recent classification of non-institutionalized patients by lateral asymmetry has delineated positive and negative syndromes associated with opposite states of hemispheric balance. The neuropsychology of the symptoms is consistent with higher left- than right hemispheric activity in the positive syndrome, and higher right- than left hemispheric activity in the negative syndrome, evidence which in turn is consistent with current theory about hemispheric influences on electrodermal responses. As all patients had Schneiderian symptoms in common this provided a three-syndrome model, a model having affinities with contemporary reports of three-factor solutions in factor analyses of clinical ratings. All approaches describe two positive syndromes and one negative syndrome. The same model applied to the schizotypal personality has produced a three-factor solution having a strong bearing on the three schizophrenia syndromes, together with evidence of imbalances in functional lateralization that are consistent with the schizophrenia model. It is proposed that the controversy surrounding the orienting and habituation anomalies in schizotypal personality, which include reduced activity, augmented activity, and irregular habituation, may be elucidated by examining relationships with the three-syndrome model and through bilateral measurement. However, provision must be made for distinctions between processes of fixed structure and dynamic function, a critical requirement in view of the relations between electrodermal reactivity and orienting to the dynamic processes of arousal, attention and anxiety. The central nervous system underpinnings of electrodermal responsiveness in schizophrenia, notably the responder-non-responder distinction, is beginning to be elucidated through neuropsychological testing and brain imaging techniques. Research is warranted to explore an integration between the syndromes which evolved from bilateral measurement, and the responder-non-responder classification which arose from considerations of limbic dysfunction. PMID- 8206801 TI - Event-related desynchronization (ERD) patterns during verbal memory tasks: effect of age. AB - Event-related desynchronization (ERD) was studied in 10 young (mean age = 19.1) and 10 older (mean age = 62.8) subjects during a verbal recognition task. The attention load of the task varied according to the difficulty of discriminating between targets and distractors. EEG recorded from 29 electrodes was used to compute ERD from 14 source derivations in 125 ms intervals. Thereafter, it was displayed as spatiotemporal maps. The results show that attention influences the characteristics of EEG desynchronization. In young subjects, ERD is more pronounced and more widespread when the attentional load is high. In the elderly, differences between the two attention conditions are less marked. ANOVA reveals main effects of attention and time. The significant 'attention x time x age group' interaction confirms the presence of different brain activation patterns in the two age groups in relation to attention load. PMID- 8206802 TI - Absolute pitch--electrophysiological evidence. AB - People who have the ability to label or to produce notes without any reference are considered to possess Absolute Pitch (AP). Others, who need a reference in order to identify the notes, possess Relative Pitch (RP). The AP ability is assumed to reflect a unique, language-like representation of non-lexical musical notes in memory. The purpose of this study was to examine this assumption by comparing Event Related Potentials (ERP) of musicians with and without AP, to lexical and non-lexical representation of musical material. Subjects were eighteen young adult musicians. Seven were AP and eleven RP. Auditory stimuli, presented through earphones, were piano notes (non-lexical) or a voice saying the note's name (lexical). Visual stimuli, presented on a computer display were note symbols (non-lexical) or letters (lexical). Subjects performed a number of tasks, combining the two modalities (visual and auditory) and stimulus types (lexical and non-lexical), and reaction times (RT), performance accuracy and evoked potentials were recorded. The tasks forced the subjects to transfer mental representations of musical material from one mode to another. Our most important findings were the differences, between groups, in the scalp distribution of P300 amplitudes. We conclude that absolute pitch possessors use the same internal language as relative pitch possessors, when possible, but the distribution of the underlying brain activity is different between AP and RP subjects. PMID- 8206803 TI - The grasp reflex from the right and left hand in human neonates indicates that the development of both cerebral hemispheres in males, but only the right hemisphere in females, is favoured by testosterone. AB - The grasp reflex was studied in relation to serum free testosterone levels in human neonates. In the total and -FS (no familial sinistrality) males, the grasp reflex (especially that from the right hand) significantly increased as testosterone increased. In the total and -FS females, there was a significant positive linear correlation between testosterone and the grasp-reflex strength from the left hand, but not from the right hand. In +FS males, there was a significant negative correlation between the grasp-reflex strength from the left hand and testosterone, but not from the right hand; there were no significant correlations in the +FS females. The right minus left (R - L) grasp-reflex strength linearly increased with testosterone in females with normal testosterone levels, but linearly decreased in females with high testosterone levels. The log R - L grasp reflex increased with testosterone in males. It was concluded that testosterone may be beneficial for the development of the left brain in -FS males and the left brain in -FS females, but may have detrimental effects on the right brain in +FS males. The growth-promoting asymmetric effects of testosterone on the brain may depend upon genetic organization of the brain. PMID- 8206804 TI - Multiband topographic EEG analysis of a simulated visuomotor aviation task. AB - Topographic EEG spectral magnitudes from 19 cortical sites were compared in 15 adult male subjects during performance of a simulated flight task and during control conditions which attempted to separately evaluate functional components of this task. Four conditions were studied, including eyes closed, a visual control, a motor control and a simulated landing task requiring integration of both visual and motor components. Each condition was repeated twice in a counterbalanced replicated measures design. A linked-ear EEG reference was used and spectral magnitudes calculated for 6 frequency bands. Decisions concerning band width and spectral transform were empirically determined. Findings indicated no significant differences between replications. A broad posterior cortical suppression of all frequencies was observed in the visual control condition. Anterior sites were affected only in the 7-12 Hz range. Additional suppression was seen during the motor control condition but limited to frontocentral sites in the 11-13 Hz band. The flight task, however, produced a further suppression at centroparietal cortex in the 9-13 Hz range. The extraction of both attentional and motor components from this task suggests that the parietal EEG activation was specific to cognitive processing. PMID- 8206805 TI - Metabolic and cardiorespiratory measures of mental effort: the effects of level of difficulty in a working memory task. AB - 24 participants (12 female) performed a continuous memory task during which metabolic, cardiorespiratory, performance, and subjective mental workload measures were taken. Task difficulty was varied using two manipulations in a within-subjects factorial design: memory load (one or three items) and temporal demand (interstimulus intervals of 2, 3, or 4 s). Males and females differed in initial metabolic rate, but did not differ in their response to the task. Memory load affected all measures, while temporal demand affected only respiration rate, performance, and subjective mental workload. Metabolic, Respiratory, Cardiovascular, and Subjective/Performance components were identified in a principal components analysis (PCA), and the Respiratory and Subjective/Performance components were affected by the task manipulations. When performance quality was examined, the Metabolic component revealed that poor performers had greater energy expenditure during the task than good performers, and the Cardiovascular component revealed that good and poor performers differed in their response to memory load and temporal demand. Cardiac and metabolic changes during mental work were not a function of overall mental effort, but were specific to the effort due to memory load and to the individual differences among participants in their ability to perform the task. However, respiration was sensitive to the mental effort associated with both memory load and temporal demand, but was not sensitive to individual differences. PMID- 8206806 TI - The self-regulation of slow potential shifts and evoked potentials: interrelationships in response to somatosensory stimulation. AB - Research on the effects of the self-regulation of event-related potentials (ERP) has failed to investigate the possible interactions and contributions of slower cortical events such as contingent negative variations (CNV) and slower DC level changes. The present study attempted to investigate such interactions by independently conditioning the ERP 200 ms poststimulus (P200) and the CNV while recording both potentials simultaneously; DC level measures were also recorded. 30 subjects attempted to increase (uptraining) or decrease (downtraining) either P200 or CNV in response to sub-painful somatosensory stimulation in a biofeedback paradigm. Following the training sessions, P200 downtrainees reported a significant decrease in their detection thresholds for the somatosensory stimuli (i.e., increased sensitivity). These results agree with some prior findings that decreased ERP amplitude in individuals is indicative of greater sensitivity in subjective pain reports. Although uptraining resulted in larger P200 amplitudes than downtraining, the difference in amplitudes between groups was not significant. CNV uptrainees achieved a higher level of pain tolerance following training. The increased CNV negativity may be associated with increased specific attentional processes that facilitate the subjects' control of, or response to, pain. CNV trainers showed a significant interaction of training over blocks of trials. Generally, there was a significant inverse correlation of P200 and CNV; as CNV amplitude became more negative, the P200 amplitude increased. DC negativity level increased over blocks for all conditions. Results indicate a complex relationship between P200, CNV and pain sensitivity. Both P200 and CNV processes are involved in pain perception, but in apparently different ways, i.e., P200 with sensitivity and CNV with tolerance. PMID- 8206807 TI - Electrical source localization of human movement-related cortical potentials. AB - Movement-related cortical potentials (MRCP) of healthy humans were analyzed with a brain electrical source analysis program for modelling equivalent electrical dipoles in order to suggest the generators of the MRCP. Both right and left voluntary self-paced index finger movements were performed by 14 subjects and MRCP were recorded on the scalp with 29 electrodes. A spatiotemporal three-dipole model was developed and it explained 94.1% of the right-hand data and 96.4% of the left-hand data. The models for right- and left-hand data were almost similar except for the different hemispheres. A midline dipole was most active during the preparatory period before the onset of voluntary movement and two contralaterally locating dipoles were most active during and immediately after the motor act. The present model did not support recently suggested bilateral activation of primary motor cortices preceding the voluntary movement. The locations, orientations and the time course of activation of the dipoles suggest the involvement of the supplementary motor area in preparation of the movement and the contralateral primary motor cortex during the execution of the movement and the contralateral primary sensory cortex following the movement. PMID- 8206808 TI - Deviate P200 and P300 in non-patient college students with high scores on the schizophrenia scale of the Minnesota Multiphasic Personality Inventory (MMPI). AB - Event-related potentials (ERPs) were examined in 16 college students who had high scores on the Schizophrenia Scale of the MMPI (HSS) but were without a hereditary disposition for major psychiatric disorders. 32 sex- and age-matched college students were used as controls. Subjects whose T scores were higher than 70 were designated the HSS subjects. ERPs were recorded during an auditory oddball task. Although neither the P300 latencies nor the P200 latencies differed between the two subject groups, the amplitudes of P300 to rare stimuli and P200 to frequent stimuli were lower in the HSS subjects than in the controls. These results suggest that deficits, both in the P300-related cognitive function to rare relevant stimuli, as well as matching and/or the comparison process for irrelevant frequent stimuli, may be present in HSS subjects. The HSS subjects, especially those with a combination of P300 and P200 deficits, even though without a hereditary diathesis for schizophrenia, may constitute one type of high risk group. PMID- 8206809 TI - Effect of the dopamine D2 antagonist sulpiride on event-related potentials and its relation to the law of initial value. AB - Effects of the dopamine antagonist sulpiride on event-related potentials (ERPs) were investigated during an auditory odd ball task in 18 healthy volunteers. Sulpiride (150 or 300 mg) or an inactive placebo was administered according to a completely randomized double-blind cross-over design. ERPs were recorded 1 h after medication was given. Sulpiride shortened the P200 latency for frequent stimuli, but tended to increase the N200 and P300 latencies for rare stimuli. Although on the whole sulpiride had no effect on the amplitudes of the ERP components in the subjects, it increased the P300 amplitudes in the low P300 amplitude subjects and decreased them in the high P300 amplitude subjects. This tendency for a bidirectional response was also found for the N100 and N200 amplitudes. A single administration of 150 or 300 mg sulpiride is considered to affect the ERP latencies and amplitudes in healthy subjects, the bidirectional response that takes place being dependent on the difference in the initial values. The results of this study are discussed in relation to the 'Law of initial value'. PMID- 8206810 TI - In memoriam Frank N. McMillan and the circle of friends of analytical psychology at Texas A & M University. PMID- 8206811 TI - To be born was the death of him: a clinical study of a self that might have been but never got born. AB - In this paper, using a pluralistic perspective on the psyche, I consider theoretical formulations concerned with the development of the self in relation to the environment. This includes discussion about how the infant interacts with its maternal environment before birth and how observation of the foetus in the womb and infant research have important implications affecting our understanding of adult psychopathology. I briefly look at the object-related nature of religious experience and the concept of the development of a representation of God. Furthermore, I explore the object-related nature of the Laius myth as the deeper realm and the homo-erotic component in the Oedipal conflict, with emphasis on the link between oracular literalism and literalizing obsessionality. Finally, I show how all of these elements manifested in the course of my work with a very disturbed male patient in whom the transferential relationship uncovered a psychopathic pocket; and how my life was put in danger when his defences took the form of an impulse to kill: he became murderous. PMID- 8206812 TI - C. G. Jung and the psychology of adult development. AB - Jung can be regarded as a founder of the psychology of adult development and ageing: against the widely held belief that events of decisive import for the formation of an individual's personality occur only within the first two decades of life, he recognized that momentous psychological changes can take place during the second half of life as well. Current appraisals of Jung's contributions in this field tend however to be reductive and simplistic. Accordingly, an attempt is made here to restore some of the complexity of Jung's thought, and to assess its potential towards the attainment of a comprehensive account of the adult condition in contemporary society. This analysis shows that aspects of his views on the developmental course of adulthood enjoy a measure of empirical support. On the other hand, the consideration of some dramatic changes that today's society is increasingly imposing upon the structure of adult life suggests that a revision of some Jungian assumptions about the latter may be in order. PMID- 8206813 TI - Cross-level analysis of the influence of local union structure on women's and men's union commitment. AB - The authors tested the influence of structural features of local unions (N = 43) on members' union commitment (N = 539) as moderated by members' gender. By using a cross-level analysis, they identified local structure with officers' ratings of innovation, formalization, and centralization. An anticipated interaction between gender and innovation was not found. However, as predicted, women's commitment was positively related to formalization and negatively related to centralization. In contrast, men's commitment was only slightly influenced by local formalization but was positively related to centralization. The need for structural redesign to enhance member's commitment, particularly among women, was discussed. PMID- 8206814 TI - Effect of newcomer involvement in work-related activities: a longitudinal study of socialization. AB - One hundred ninety-three new PhD students provided data on entry to their doctoral programs and again 9 months later. This longitudinal design was used to extend the socialization literature by testing the influence of newcomer involvement on socialization, controlling for newcomer perceptions on entry, and allowing for a dynamic view of socialization stages. Individuals who had collected information that they perceived as realistic, who had attended the same institution for their undergraduate degree, and who had past research experience were more involved in their doctoral programs, were more engaged in doctoral research, had less role conflict, felt more accepted, and were more productive as measured by objective outcomes. In addition, those individuals who were actively involved in their doctoral program were better accommodated and had greater productivity. Accommodation variables predicted commitment, and activity measures predicted submissions. PMID- 8206815 TI - Mental and physical countermeasures reduce the accuracy of polygraph tests. AB - Effects of countermeasures on the control-question polygraph test were examined in an experiment with 120 Ss recruited from the general community. Ss were given polygraph tests by an examiner who used field techniques. Twenty Ss were innocent, and of the 100 guilty Ss, 80 were trained in the use of either a physical countermeasure (biting the tongue or pressing the toes to the floor) or a mental countermeasure (counting backward by 7) to be applied while control questions were being presented during their examinations. The mental and physical countermeasures were equally effective: Each enabled approximately 50% of the Ss to defeat the polygraph test. The strongest countermeasure effects were observed in the cardiovascular measures. Moreover, the countermeasures were difficult to detect either instrumentally or through observation. PMID- 8206816 TI - Lost but not forgotten details: repeated eyewitness recall leads to reminiscence but not hypermnesia. AB - In 2 experiments, the effects on participants' memory and confidence of repeatedly describing a videotaped crime and of the opportunity to review a previous description were investigated. E. Scrivner and M. A. Safer (1988) demonstrated that witnesses' successive attempts to describe such events can lead to the recall of more new information in comparison with the amount forgotten (i.e., increased net recall, or hypermnesia). In Experiment 1, a more forensically relevant procedure was used, and no support for hypermnesia was found. Witnesses did recall significantly more new information across attempts, but the amount did not exceed how much was forgotten (i.e., increased gross recall, or reminiscence). The opportunity to review a previous statement had no effect on the number of items recalled. In Experiment 2, the more traditional, repeated-recall procedure used by Scrivner and Safer was applied, and their finding of hypermnesia was replicated with the present study's materials. PMID- 8206817 TI - Peer influence on smoking initiation during early adolescence: a comparison of group members and group outsiders. AB - In this study, the authors compared group members' and group outsiders' susceptibility to the influence of their friends' smoking. Ss were nonsmokers in Grade 7 who were observed for 1 year. Consistent with their hypothesis, the authors found that group outsiders (Ss who did not have reciprocal friends) were affected more by the smoking of their best friend and by the overall level of smoking among their friends than group members were. Furthermore, this peer influence was strongest for teens who were very concerned about their friends' reactions to their substance use. In addition, consistency in smoking status was related to the formation, but not the breakdown, of reciprocal friendships. Results indicated that teenagers may view smoking as a vehicle for entering a desired friendship group. The authors suggest ways that prevention programs might address this mechanism for adolescent smoking initiation. PMID- 8206818 TI - Using socially fair treatment to promote acceptance of a work site smoking ban. AB - Announcements of a work site smoking ban were made to 732 clerical workers. The presentations differed in the amount of information given about the need for the ban and the degree of interpersonal sensitivity shown over the personal impact of the ban. Immediately after the announcement, questionnaires were completed to assess participants' acceptance of the ban. High amounts of information thoroughness and of social sensitivity, given separately, enhanced acceptance of the ban, but their combined effects were even greater. Although heavy smokers were least accepting of the ban, they showed the greatest incremental gain in acceptance after exposure to thorough information presented in a highly sensitive manner. By contrast, nonsmokers' acceptance of the ban was uniformly unaffected by the way it was presented to them. Regardless of how much they smoked, all participants recognized the procedural fairness associated with giving thorough information in a socially sensitive manner. PMID- 8206819 TI - Influence of sex role stereotypes on personnel decisions of black managers. AB - The influence of sex role stereotypes on the hiring decisions of Black managers was investigated. A 2 x 2 x 2 factorial design and multivariate analysis of variance were used to analyze the relationship between sex of respondent, sex of applicant, and job sex type. Respondents were 131 managers who rated either a Black man or a Black woman for a stereotypically female- or male-sex-typed job on a Likert-type scale. There were significant findings on 3 of the 7 dependent variables--potential to work, potential to complete tasks, and technical potential--on which men were rated more favorably for the male-sex-typed job and women were rated more favorably for the female-sex-typed job. However, sex stereotyping was more pronounced for the female-sex-stereotyped job than for the male-sex-stereotyped job on some dependent variables. Results are discussed in regard to the unique experiences of Black men and women in American society. PMID- 8206820 TI - Transcriptional regulation by TrsN of conjugative transfer genes on staphylococcal plasmid pGO1. AB - The major conjugative transfer gene cluster of staphylococcal plasmid pGO1 (trs) consists of 13 open reading frames (trsA to trsM) transcribed from one DNA strand and a single 189-bp open reading frame (trsN) within the first 348 bp of trs that is transcribed divergently. Promoter regions for trsN and trsA partially overlap. TrsN, a 7,181-Da protein, was purified as a fusion to glutathione S-transferase and found to have DNA-binding activity. Increasing concentrations of the fusion protein progressively retarded the gel migration of PCR-generated DNA fragments containing predicted promoters 5' to trsL, trsA, and trsN. The target sequences contained areas of identity, including regions of dyad symmetry, that were protected in DNase I footprinting studies. The binding of TrsN to its trsL target was required for this target DNA to be stably introduced into Staphylococcus aureus on a high-copy-number vector. Provision of excess TrsN from this high-copy number vector in S. aureus decreased beta-galactosidase activity from a trsL-lacZ transcriptional fusion and decreased pGO1 conjugation frequency. Conversely, both transcription and conjugation increased in the presence of excess trsL target. We propose that TrsN negatively regulates the transcription of genes essential for conjugative transfer by binding to regions 5' to their translational start sites. PMID- 8206821 TI - Siderophore activity of myo-inositol hexakisphosphate in Pseudomonas aeruginosa. AB - myo-Inositol hexakisphosphate (InsP6), which is found in soil and most, if not all, plant and animal cells, has been estimated to have an affinity for Fe3+ in the range of 10(25) to 10(30) M-1. In this report, we demonstrate that the Fe InsP6 complex has siderophore activity and is able to reverse the iron-restricted growth inhibition of Pseudomonas aeruginosa by ethylene diamine di(o hydroxyphenyl)acetic acid. With 55Fe-InsP6 in transport studies, iron uptake is strongly iron regulated, being repressed after growth in iron-replete conditions and inhibited by treatment with potassium cyanide and carbonyl cyanide m chlorophenylhydrazone. The kinetics of iron transport revealed a Km of 100 nM. Self-displacement of binding of [3H]InsP6 to isolated membranes by InsP6 revealed a single class of binding sites (Kd = 143 +/- 6 nM; Hill coefficient, 1.1 +/- 0.1). The binding of [3H]InsP6 to membranes was not dependent on whether cells had been grown under conditions of high or low iron concentrations. We believe that this is the first report of inositol polyphosphate activity in prokaryotic cells. PMID- 8206822 TI - Purification and in vitro activities of the native nitrogen fixation control proteins NifA and NifL. AB - The prokaryotic enhancer-binding protein NifA stimulates transcription at a distance by binding to sequences upstream of nitrogen fixation (nif) promoters and catalyzing the formation of open promoter complexes by RNA polymerase containing the alternative sigma factor, sigma 54. The activity of NifA in vivo is modulated by the negative regulatory protein NifL in response to environmental oxygen and fixed nitrogen. To date, a detailed biochemical analysis of these proteins from the model diazotroph Klebsiella pneumoniae has been hindered by their insolubility. We have now purified NifA and NifL from Azotobacter vinelandii in their native form. NifA is competent in specific DNA binding, transcriptional activation, and response to negative regulation by NifL in vitro. In contrast to the conserved mechanism of phosphotransfer demonstrated by other two-component regulatory systems, our results support a model in which NifL regulates the activity of NifA via a protein-protein steric block interaction rather than a catalytic modification of NifA. PMID- 8206823 TI - Isolation and characterization of the Methylophilus sp. strain DM11 gene encoding dichloromethane dehalogenase/glutathione S-transferase. AB - The restricted facultative methylotroph Methylophilus sp. strain DM11 utilizes dichloromethane as the sole carbon and energy source. It differs from other dichloromethane-utilizing methylotrophs by faster growth on this substrate and by possession of a group B dichloromethane dehalogenase catalyzing dechlorination at a fivefold-higher rate than the group A enzymes of slow-growing strains. We isolated dcmA, the structural gene of the strain DM11 dichloromethane dehalogenase, to elucidate its relationship to the previously characterized dcmA gene of Methylobacterium sp. strain DM4, which encodes a group A enzyme. Nucleotide sequence determination of dcmA from strain DM11 predicts a protein of 267 amino acids, corresponding to a molecular mass of 31,197 Da. The 5' terminus of in vivo dcmA transcripts was determined by primer extension to be 70 bp upstream of the translation initiation codon. It was preceded by a putative promoter sequence with high resemblance to the Escherichia coli sigma 70 consensus promoter sequence. dcmA and 130 bp of its upstream sequence were brought under control of the tac promoter and expressed in E. coli to approximately 20% of the total cellular protein by induction with isopropylthiogalactopyranoside (IPTG) and growth at 25 degrees C. Expression at 37 degrees C led to massive formation of inclusion bodies. Comparison of the strain DM11 and strain DM4 dichloromethane dehalogenase sequences revealed 59% identity at the DNA level and 56% identity at the protein level, thus indicating an ancient divergence of the two enzymes. Both dehalogenases are more closely related to eukaryotic class theta glutathione S-transferases than to a number of bacterial glutathione S-transferases. PMID- 8206824 TI - Characterization of the isocitrate lyase gene from Corynebacterium glutamicum and biochemical analysis of the enzyme. AB - Isocitrate lyase is a key enzyme in the glyoxylate cycle and is essential as an anaplerotic enzyme for growth on acetate as a carbon source. It is assumed to be of major importance in carbon flux control in the amino acid-producing organism Corynebacterium glutamicum. In crude extracts of C. glutamicum, the specific activities of isocitrate lyase were found to be 0.01 U/mg of protein after growth on glucose and 2.8 U/mg of protein after growth on acetate, indicating tight regulation. The isocitrate lyase gene, aceA, was isolated, subcloned, and characterized. The predicted gene product of aceA consists of 432 amino acids (M(r), 47,228) and shows up to 57% identity to the respective enzymes from other organisms. Downstream of aceA, a gene essential for thiamine biosynthesis was identified. Overexpression of aceA in C. glutamicum resulted in specific activities of 0.1 and 7.4 U/mg of protein in minimal medium containing glucose and acetate, respectively. Inactivation of the chromosomal aceA gene led to an inability to grow on acetate and to the absence of any detectable isocitrate lyase activity. Isocitrate lyase was purified to apparent homogeneity and subjected to biochemical analysis. The native enzyme was shown to be a tetramer of identical subunits, to exhibit an ordered Uni-Bi mechanism of catalysis, and to be effectively inhibited by 3-phosphoglycerate, 6-phosphogluconate, phosphoenolpyruvate, fructose-1,6-bisphosphate, and succinate. PMID- 8206825 TI - Regulation of the glucose:H+ symporter by metabolite-activated ATP-dependent phosphorylation of HPr in Lactobacillus brevis. AB - Lactobacillus brevis takes up glucose and the nonmetabolizable glucose analog 2 deoxyglucose (2DG), as well as lactose and the nonmetabolizable lactose analoge thiomethyl beta-galactoside (TMG), via proton symport. Our earlier studies showed that TMG, previously accumulated in L. brevis cells via the lactose:H+ symporter, rapidly effluxes from L. brevis cells or vesicles upon addition of glucose and that glucose inhibits further accumulation of TMG. This regulation was shown to be mediated by a metabolite-activated protein kinase that phosphorylase serine 46 in the HPr protein. We have now analyzed the regulation of 2DG uptake and efflux and compared it with that of TMG. Uptake of 2DG was dependent on an energy source, effectively provided by intravesicular ATP or by extravesicular arginine which provides ATP via an ATP-generating system involving the arginine deiminase pathway. 2DG uptake into these vesicles was not inhibited, and preaccumulated 2DG did not efflux from them upon electroporation of fructose 1,6-diphosphate or gluconate 6-phosphate into the vesicles. Intravesicular but not extravesicular wild-type or H15A mutant HPr of Bacillus subtilis promoted inhibition (53 and 46%, respectively) of the permease in the presence of these metabolites. Counterflow experiments indicated that inhibition of 2DG uptake is due to the partial uncoupling of proton symport from sugar transport. Intravesicular S46A mutant HPr could not promote regulation of glucose permease activity when electroporated into the vesicles with or without the phosphorylated metabolites, but the S46D mutant protein promoted regulation, even in the absence of a metabolite. The Vmax but not the Km values for both TMG and 2DG uptake were affected. Uptake of the natural, metabolizable substrates of the lactose, glucose, mannose, and ribose permeases was inhibited by wild-type HPr in the presence of fructose 1,6-diphosphate or by S46D mutant HPr. These results establish that HPr serine phosphorylation by the ATP-dependent, metabolite activated HPr kinase regulates glucose and lactose permease activities in L. brevis and suggest that other permeases may also be subject to this mode of regulation. PMID- 8206826 TI - RpoN (sigma 54) is required for conversion of phenol to catechol in Acinetobacter calcoaceticus. AB - Members of the sigma 54 protein family, encoded by rpoN, are required for the transcription of genes associated with specialized metabolic functions. The ability to grow with phenol appears to be a specialized trait because it is expressed by few of the microorganisms that grow with catechol, the metabolic product of phenol monooxygenase. A mutation preventing the expression of phenol monooxygenase in the bacterial strain Acinetobacter calcoaceticus NCIB8250 was complemented by wild-type DNA segments containing an open reading frame encoding a member of the sigma 54 protein family. DNA sequencing revealed a second open reading frame, designated ORF2, directly downstream of A. calcoaceticus rpoN. The locations of both ORF2 and the 113-residue amino acid sequence of its product are highly conserved in other bacteria. The mutation preventing the expression of rpoN results in an opal codon that terminates the translation of RpoN at a position corresponding to Trp-91 in the 483-residue amino acid sequence of the wild-type protein. Negative autoregulation of rpoN was suggested by the fact that the mutation inactivating RpoN enhanced the transcription of rpoN. Primer extension revealed independent transcription start sites for rpoN and ORF2. PMID- 8206827 TI - In vivo damage and recA-dependent repair of plasmid and chromosomal DNA in the radiation-resistant bacterium Deinococcus radiodurans. AB - Deinococcus radiodurans R1 and other members of this genus share extraordinary resistance to the lethal and mutagenic effects of ionizing radiation. We have recently identified a RecA homolog in strain R1 and have shown that mutation of the corresponding gene causes marked radiosensitivity. We show here that following high-level exposure to gamma irradiation (1.75 megarads, the dose required to yield 37% of CFU for plateau-phase wild-type R1), the wild-type strain repairs > 150 double-strand breaks per chromosome, whereas a recA defective mutant (rec30) repairs very few or none. A heterologous Escherichia coli-D. radiodurans shuttle plasmid (pMD68) was constructed and found to be retained in surviving D. radiodurans R1 and rec30 following any radiation exposure up to the highest dose tested, 3 megarads. Plasmid repair was monitored in vivo following irradiation with 1.75 megarads in both R1/pMD68 and rec30/pMD68. Immediately after irradiation, plasmids from both strains contained numerous breaks and failed to transform E. coli. While irradiation with 1.75 megarads was lethal to rec30 cultures, a small amount of supercoiled plasmid was regenerated, but it lacked the ability to transform E. coli. In contrast, wild type cultures showed a cell division arrest of about 10 h, followed by exponential growth. Supercoiled plasmid was regenerated at normal levels, and it readily transformed E. coli. These studies show that D. radiodurans retains a heterologous plasmid following irradiation and repairs it with the same high efficiency as its chromosomal DNA, while the repair defect in rec30 prevents repair of the plasmid. Taken together, the results of this study suggest that plasmid DNA damaged in vivo in D. radiodurans is repaired by recA-dependent mechanisms similar to those employed in the repair of chromosomal DNA. PMID- 8206828 TI - Quantification of the regulation of glycerol and maltose metabolism by IIAGlc of the phosphoenolpyruvate-dependent glucose phosphotransferase system in Salmonella typhimurium. AB - The amount of IIAGlc, one of the proteins of the phosphoenolpyruvate:glucose phosphotransferase system (PTS), was modulated over a broad range with the help of inducible expression plasmids in Salmonella typhimurium. The in vivo effects of different levels of IIAGlc on glycerol and maltose metabolism were studied. The inhibition of glycerol uptake, by the addition of a PTS sugar, was sigmoidally related to the amount of IIAGlc. For complete inhibition of glycerol uptake, a minimal ratio of about 3.6 mol of IIAGlc to 1 mol of glycerol kinase (tetramer) was required. Varying the level of IIAGlc (from 0 to 1,000% of the wild-type level) did not affect the growth rate on glycerol, the rate of glycerol uptake, or the synthesis of glycerol kinase. In contrast, the growth rate on maltose, the rate of maltose uptake, and the synthesis of the maltose-binding protein increased two- to fivefold with increasing levels of IIAGlc. In the presence of cyclic AMP, the maximal levels were obtained at all IIAGlc concentrations. The synthesis of the MalK protein, the target of IIAGlc, was not affected by varying the levels of IIAGlc. The inhibition of maltose uptake was sigmoidally related to the amount of IIAGlc. For complete inhibition of maltose uptake by a PTS sugar, a ratio of about 18 mol of IIAGlc to 1 mol of MalK protein (taken as a dimer) was required. PMID- 8206829 TI - Acetoin catabolic system of Klebsiella pneumoniae CG43: sequence, expression, and organization of the aco operon. AB - A cosmid clone which was capable of depleting acetoin in vivo was isolated from a library of Klebsiella pneumoniae CG43 cosmids. The smallest functional subclone contained a 3.9-kb DNA fragment of the cosmid clone. Sequencing of the DNA fragment revealed three open reading frames (ORFs A, B, and C) encoding polypeptides of 34, 36, and 52 kDa, respectively. The presence of these proteins was demonstrated by expression of the recombinant DNA clone in Escherichia coli. Considerable similarities between the deduced amino acid sequences of the ORFs and those of the following enzymes were found: acetoin dissimilation enzymes, pyruvate dehydrogenase complex, 2-oxoglutarate dehydrogenase complex, and branched-chain 2-oxo acid dehydrogenase complex of various origins. Activities of these enzymes, including acetoin-dependent dichlorophenolin-dohenol oxidoreductase and dihydrolipoamide acetyltransferase, were detected in the extracts of E. coli harboring the genes encoding products of the three ORFs. Although not required for acetoin depletion in vivo, a possible fourth ORF (ORF D), located 39 nucleotides downstream of ORF C, was also identified. The deduced N-terminal sequence of the ORF D product was highly homologous to the dihydrolipoamide dehydrogenases of several organisms. Primer extension analysis identified the transcriptional start of the operon as an A residue 72 nucleotides upstream of ORF A. PMID- 8206831 TI - Identification of the genes encoding NAD(P)H-flavin oxidoreductases that are similar in sequence to Escherichia coli Fre in four species of luminous bacteria: Photorhabdus luminescens, Vibrio fischeri, Vibrio harveyi, and Vibrio orientalis. AB - Genes encoding NAD(P)H-flavin oxidoreductases (flavin reductases) similar in both size and sequence to Fre, the most abundant flavin reductase in Escherichia coli, were identified in four species of luminous bacteria, Photorhabdus luminescens (ATCC 29999), Vibrio fischeri (ATCC 7744), Vibrio harveyi (ATCC 33843), and Vibrio orientalis (ATCC 33934). Nucleotide sequence analysis showed Fre-like flavin reductases in P. luminescens and V. fischeri to consist of 233 and 236 amino acids, respectively. As in E. coli Fre, Fre-like enzymes in luminous bacteria preferably used riboflavin as an electron acceptor when NADPH was used as an electron donor. These enzymes also were good suppliers of reduced flavin mononucleotide (FMNH2) to the bioluminescence reaction. In V. fischeri, the Fre like enzyme is a minor flavin reductase representing < 10% of the total FMN reductase. That the V. fischeri Fre-like enzyme has no appreciable homology in amino acid sequence to the major flavin reductase in V. fischeri, FRase I, indicates that at least two different types of flavin reductases supply FMNH2 to the luminescence system in V. fischeri. Although Fre-like flavin reductases are highly similar in sequence to luxG gene products (LuxGs), Fre-like flavin reductases and LuxGs appear to constitute two separate groups of flavin associated proteins. PMID- 8206830 TI - Identification of the gene encoding the major NAD(P)H-flavin oxidoreductase of the bioluminescent bacterium Vibrio fischeri ATCC 7744. AB - The gene encoding the major NAD(P)H-flavin oxidoreductase (flavin reductase) of the luminous bacterium Vibrio fischeri ATCC 7744 was isolated by using synthetic oligonucleotide probes corresponding to the N-terminal amino acid sequence of the enzyme. Nucleotide sequence analysis suggested that the major flavin reductase of V. fischeri consisted of 218 amino acids and had a calculated molecular weight of 24,562. Cloned flavin reductase expressed in Escherichia coli was purified virtually to homogeneity, and its basic biochemical properties were examined. As in the major flavin reductase in crude extracts of V. fischeri, cloned flavin reductase showed broad substrate specificity and served well as a catalyst to supply reduced flavin mononucleotide (FMNH2) to the bioluminescence reaction. The major flavin reductase of V. fischeri not only showed significant similarity in amino acid sequence to oxygen-insensitive NAD(P)H nitroreductases of Salmonella typhimurium, Enterobacter cloacae, and E. coli but also was associated with a low level of nitroreductase activity. The major flavin reductase of V. fischeri and the nitroreductases of members of the family Enterobacteriaceae would thus appear closely related in evolution and form a novel protein family. PMID- 8206832 TI - Vibrio harveyi NADPH-flavin oxidoreductase: cloning, sequencing and overexpression of the gene and purification and characterization of the cloned enzyme. AB - NAD(P)H-flavin oxidoreductases (flavin reductases) from luminous bacteria catalyze the reduction of flavin by NAD(P)H and are believed to provide the reduced form of flavin mononucleotide (FMN) for luciferase in the bioluminescence reaction. By using an oligonucleotide probe based on the partial N-terminal amino acid sequence of the Vibrio harveyi NADPH-FMN oxidoreductase (flavin reductase P), a recombinant plasmid, pFRP1, was obtained which contained the frp gene encoding this enzyme. The DNA sequence of the frp gene was determined; the deduced amino acid sequence for flavin reductase P consists of 240 amino acid residues with a molecular weight of 26,312. The frp gene was overexpressed, apparently through induction, in Escherichia coli JM109 cells harboring pFRP1. The cloned flavin reductase P was purified to homogeneity by following a new and simple procedure involving FMN-agarose chromatography as a key step. The same chromatography material was also highly effective in concentrating diluted flavin reductase P. The purified enzyme is a monomer and is unusual in having a tightly bound FMN cofactor. Distinct from the free FMN, the bound FMN cofactor showed a diminished A375 peak and a slightly increased 8-nm red-shifted A453 peak and was completely or nearly nonfluorescent. The Kms for FMN and NADPH and the turnover number of this flavin reductase were determined. In comparison with other flavin reductases and homologous proteins, this flavin reductase P shows a number of distinct features with respect to primary sequence, redox center, and/or kinetic mechanism. PMID- 8206833 TI - Characterization of genetic determinants for R body synthesis and assembly in Caedibacter taeniospiralis 47 and 116. AB - Caedibacter taeniospiralis, an obligate bacterial endosymbiont of Paramecium tetraurelia, confers a killing trait upon its host paramecium. Type 51 R bodies (refractile inclusion bodies) are synthesized by these endosymbionts and are required for expression of the killing trait. The nucleotide sequence of the genetic determinants for type 51 R body synthesis and assembly was determined for C. taeniospiralis 47 and 116. Three independently transcribed genes (rebA, rebB, and rebC) were characterized. To date these are the only genes from C. taeniospiralis to be sequenced and characterized. DNA regulatory regions are recognized by Escherichia coli, and codon usage appears similar to that in E. coli. A fourth open reading frame with appropriate regulatory sequences was found within the reb locus, but no evidence was obtained to suggest that this putative gene is expressed in E. coli. The R body-encoding sequences from both strains are identical. Two-dimensional gel electrophoresis of deletion derivatives shows that two polymerization events are involved in R body assembly. One polymerization event requires only RebB and RebC; the other requires all three proteins. Expression of RebC is necessary for the posttranslational modification of RebA and RebB into species with three and two different molecular weights, respectively. In the presence of RebC, each species of RebB with a different molecular weight has six different isoelectric points. PMID- 8206835 TI - Functional role of the Ti plasmid-encoded catabolic mannopine cyclase in mannityl opine catabolism by Agrobacterium spp. AB - Catabolic mannopine (MOP) cyclase encoded by Ti or Ri plasmids lactonizes MOP to agropine (AGR). The gene of the octopine-type Ti plasmid pTi15955 encoding the catabolic MOP cyclase enzyme previously was localized to a 1.6-kb segment within a cosmid clone, pYDH208. A subclone containing only this region complemented the AGR catabolism-negative phenotype conferred by a derivative of the octopine-type plasmid pTiB6S3 containing a Tn7 insertion in the region encoding the MOP cyclase enzyme. Uptake assays of strains harboring pRiA4 or pArA4a, along with complementation analyses, indicate that MOP cyclase is not sufficient for catabolism of AGR but that the strains must also express an AGR transport system. To determine the requirement for MOP cyclase in opine catabolism unequivocally, a site-specific, nonpolar deletion mutation abolishing only MOP cyclase activity was introduced into pYDH208, a cosmid clone that confers utilization of MOP, AGR, and mannopinic acid (MOA). Strains harboring this MOP cyclase-negative mutant clone, pYDPH208, did not utilize AGR but continued to utilize MOP. Growth on AGR was restored in this strain upon introduction of clones encoding the pTi15955 derived catabolic or anabolic MOP cyclase genes. The induction pattern of MOA catabolism shown by strain NT1 harboring the MOP cyclase-deficient pYDPH208 suggests that AGR is converted into MOP by MOP cyclase and that MOP, but not AGR, induces catabolism of MOA. Genetic and biochemical analyses of MOP and AGR metabolism suggest that only the conversion of AGR to MOP is directly involved in catabolism of AGR, even though the reaction catalyzed by MOP cyclase predominantly lies in the lactonization of MOP to AGR. PMID- 8206834 TI - The cobT gene of Salmonella typhimurium encodes the NaMN: 5,6 dimethylbenzimidazole phosphoribosyltransferase responsible for the synthesis of N1-(5-phospho-alpha-D-ribosyl)-5,6-dimethylbenzimidazole, an intermediate in the synthesis of the nucleotide loop of cobalamin. AB - We present in vitro evidence which demonstrates that CobT is the nicotinate nucleotide:5,6-dimethylbenzimidazole (DMB) phosphoribosyltransferase (EC 2.4.2.21) that catalyzes the synthesis of N1-(5-phospho-alpha-D-ribosyl)-5,6 dimethylbenzimidazole, a biosynthetic intermediate of the pathway that assembles the nucleotide loop of cobalamin in Salmonella typhimurium. Mutants previously isolated as DMB auxotrophs are shown by physical and genetic mapping studies and complementation studies to carry lesions in cobT. Explanations for this unexpected phenotype of cobT mutants are discussed. The expected nucleotide loop assembly phenotype of cobT mutants can be observed only in a specific genetic background, i.e., cobB deficient, an observation that is consistent with the existence of an alternative CobT function (G. A. O'Toole, M. R. Rondon, and J. C. Escalante-Semerena, J. Bacteriol. 175:3317-3326, 1993). Computer analysis of CobT homologs showed that at the amino acid level, enteric CobT proteins were 80% identical whereas Pseudomonas denitrificans and Rhizobium meliloti CobT proteins were 95% identical. Interestingly, the degree of identity between enteric and nonenteric CobT homologs was only 30%. The same pattern of homologies was reported for the S. typhimurium CobA, Escherichia coli BtuR, and P. denitrificans CobO proteins (S.-J. Suh and J.C. Escalante-Semerena, Gene 129:93-97, 1993), suggesting evolutionary divergence between the cob genes found in the enteric bacteria E. coli and S. typhimurium and those found in P. denitrificans and R. meliloti. PMID- 8206836 TI - Purification and characterization of periplasmic alpha-amylase from Xanthomonas campestris K-11151. AB - Xanthomonas campestris K-11151, isolated from soil, produced a periplasmic alpha amylase of a new type. The enzyme was purified to homogeneity, as shown by several criteria. The purified enzyme showed almost the same activities on alpha , beta-, and gamma-cyclodextrins, soluble starch, and amylose. Moreover, it was active on branched cyclodextrins, pullulan, and maltose but not on glycogen. Kinetic analysis showed that alpha-cyclodextrin was the best substrate among the cyclodextrins. The substrate specificity suggested that this enzyme had the combined activities of alpha-amylase, cyclodextrinase, and neopullulanase. PMID- 8206837 TI - Isolation and characterization of a gene, pmrD, from Salmonella typhimurium that confers resistance to polymyxin when expressed in multiple copies. AB - We have isolated from Salmonella typhimurium a gene, designated pmrD, that confers resistance to the membrane-damaging drug, polymyxin B when expressed from the medium-copy-number plasmid pHSG576. The gene maps to 46 min on the standard genetic map, near the menB gene, and is therefore distinct from the previously described pmrA locus. We have mapped the polymyxin resistance activity to a 1.3 kb ClaI-PvuII fragment which contains a small open reading frame that could encode an 85-amino-acid peptide. When an omega-Tet insertion was made into the putative pmrD open reading frame (pmrD2::omega-Tet), the resulting plasmid no longer conferred polymyxin resistance, whereas an omega-Tet insertion into vector sequences had no effect. Maxicell analysis confirmed that a protein of the expected size is made in vivo. The PmrD protein shows no significant homology to any known protein, but it does show limited homology across the active site of the p15 acid protease from Rous sarcoma virus, indicating that the protein may have proteolytic activity. However, changing the aspartic acid residue at the putative active site to alanine reduced but did not eliminate polymyxin resistance. When pmrD2::omega-Tet replaced the chromosomal copy of pmrD, the resulting strain showed wild-type sensitivity to polymyxin and could be complemented to resistance by a plasmid that carried pmrD. The pmrA505 allele confers resistance to polymyxin when present in single copy on the chromosome or when present on a plasmid in pmrA+ pmrD+ cells. In combination with the pmrD(2):: Tet mutation, the effect o the pmrA505 allele on polymyxin resistance was reduced, whether pmrA505 was present in the chromosome or on a plasmid. Conversely, a strain carrying an insertion in pmrA could be complemented to polymyxin resistance by a plasmid carrying the pmrA505 allele but not by a plasmid carrying pmrD. On the basis of these results, we suggest that polymyxin resistance is mediated by an interaction between PmrA or a PmrA-regulated gene product and PmrD. PMID- 8206838 TI - Role of the FliA-FlgM regulatory system on the transcriptional control of the flagellar regulon and flagellar formation in Salmonella typhimurium. AB - In the flagellar regulon of Salmonella typhimurium, the flagellar operons are divided into three classes, 1, 2, and 3, with respect to transcriptional hierarchy. The class 2 operons are controlled positively by the class 1 genes, flhD and flhC. The class 3 operons are controlled positively by fliA and negatively by flgM. It has been shown that FliA is a sigma factor specific for class 3, whereas FlgM is an anti-sigma factor which binds FliA to prevent its association with RNA polymerase core enzyme. Therefore, the FliA-FlgM regulatory system has been believed to control specifically the class 3 operons. In the present study, we showed that the flgM mutation enhanced the expression of class 2 by more than fivefold. When a fliA mutation was present simultaneously, this enhancement was not observed. These results indicate that the FliA-FlgM regulatory system is involved not only in the expression of class 3 but also in that of class 2. However, though neither flhD nor flhC mutants could express the class 2 operons, the fliA mutants permitted the basal-level expression of those operons. Therefore, FlhD and FlhC are indispensable for the expression of class 2, whereas FliA is required only for its enhancement in the FlgM-depletion condition. Furthermore, we showed that the flgM mutation resulted in a two- to threefold increase in flagellar number. On the basis of these results, we propose that the relative concentration of FliA and FlgM may play an important role in the determination of flagellar numbers produced by a single cell. PMID- 8206839 TI - Comparative analysis of functional and structural features in the primase dependent priming signals, G sites, from phages and plasmids. AB - The primase-dependent priming signals, G sites, are directly recognized by the Escherichia coli primase (dnaG gene product) and conduct the synthesis of primer RNAs. In nucleotide sequence and secondary structure, there is no striking resemblance between the phage- and plasmid-derived G sites, except for the limited sequence homology near the start position of primer RNA synthesis. In this study, we analyzed the structure and function of a G site of plasmid R100, G site (R100), and discovered the necessity of the coexistence of two domains (domains I and III), which contains blocks A, B, and C, which are nucleotide sequences highly conserved among the plasmid-derived G sites. However, neither the internal region, domain II, between domains I and III nor the potential secondary structure proposed by Bahk et al. (J. D. Bahk, N. Kioka, H. Sakai, and T. Komano, Plasmid 20:266-270, 1988) is essential for single-stranded DNA initiation activity. Furthermore, chimeric G sites constructed between a G site of phage G4, G site(G4), and G site(R100) maintained significant single-stranded DNA initiation activities. These results strongly suggest that phage- and plasmid derived G sites have functionally equivalent domains. The primase-dependent priming mechanisms of phage- and plasmid-derived G sites are discussed. PMID- 8206840 TI - Biochemical and molecular characterization of the Clostridium magnum acetoin dehydrogenase enzyme system. AB - E2 (dihydrolipoamide acetyltransferase) and E3 (dihydrolipoamide dehydrogenase) of the Clostridium magnum acetoin dehydrogenase enzyme system were copurified in a three-step procedure from acetoin-grown cells. The denatured E2-E3 preparation comprised two polypeptides with M(r)s of 49,000 and 67,000, respectively. Microsequencing of both proteins revealed identical amino acid sequences. By use of oligonucleotide probes based on the N-terminal sequences of the alpha and beta subunits of E1 (acetoin dehydrogenase, thymine PPi dependent), which were purified recently (H. Lorenzl, F.B. Oppermann, B. Schmidt, and A. Steinbuchel, Antonie van Leeuwenhoek 63:219-225, 1993), and of E2-E3, structural genes acoA (encoding E1 alpha), acoB (encoding E1 beta), acoC (encoding E2), and acoL (encoding E3) were identified on a single ClaI restriction fragment and expressed in Escherichia coli. The nucleotide sequences of acoA (978 bp), acoB (999 bp), acoC (1,332 bp), and acoL (1,734 bp), as well as those of acoX (996 bp) and acoR (1,956 bp), were determined. The amino acid sequences deduced from acoA, acoB, acoC, and acoL for E1 alpha (M(r), 35,532), E1 beta (M(r), 35,541), E2 (M(r), 48,149), and E3 (M(r), 61,255) exhibited striking similarities to the amino acid sequences of the corresponding components of the Pelobacter carbinolicus acetoin dehydrogenase enzyme system and the Alcaligenes eutrophus acetoin-cleaving system, respectively. Significant homologies to the enzyme components of various 2-oxo acid dehydrogenase complexes were also found, indicating a close relationship between the two enzyme systems. As a result of the partial repetition of the 5' coding region of acoC into the corresponding part of acoL, the E3 component of the C. magnum acetoin dehydrogenase enzyme system contains an N-terminal lipoyl domain, which is unique among dihydrolipoamide dehydrogenases. We found strong similarities between the AcoR and AcoX sequences and the A. eutrophus acoR gene product, which is a regulatory protein required for expression of the A. eutrophus aco genes, and the A. eutrophus acoX gene product, which has an unknown function, respectively. The aco genes of C. magnum are probably organized in one single operon (acoABXCL); acoR maps upstream of this operon. PMID- 8206841 TI - Genetic and biochemical analysis of the flagellar hook of Treponema phagedenis. AB - The periplasmic flagellum of Treponema phagedenis consists of the flagellar filament and hook-basal body. We report here a characterization of the hook gene and flagellar hook of T. phagedenis, and in the process of this analysis we found evidence that the hook polypeptide is likely cross-linked in situ. A T. phagedenis genomic library was screened with a Treponema pallidum antiserum, and the DNA segments from several positive plaques were subcloned and sequenced. DNA sequencing of two overlapping segments revealed a 1,389-nucleotide (nt) open reading frame (ORF) with a deduced amino acid sequence that was 36% identical to that of FlgE, the hook polypeptide of Salmonella typhimurium. This gene was designated T. phagedenis flgE. Beginning at 312 nt downstream from flgE was a partial ORF of 486 nt with a deduced amino acid sequence that was 33% identical to that of MotA of Bacillus subtilis, a polypeptide that enables flagellar rotation. Upstream of flgE, separated by 39 nt, was a partial (291-nt) ORF with a deduced amino acid sequence that was homologous to that of ORF8, a polypeptide of unknown function located in an operon encoding polypeptides involved in motility of B. subtilis. The T. phagedenis flgE gene was cloned into an Escherichia coli protein expression plasmid, and the purified recombinant protein was used to prepare a FlgE antiserum. Western blots (immunoblots) of whole-cell lysates probed with this antiserum revealed a 55-kDa polypeptide and a ladder of polypeptide bands with increasing molecular masses. T. phagedenis hooks were then isolated and purified, and electron microscopic analysis revealed that the morphology of the hooks resembled that in other bacteria. The hooks were slightly curved and had an average length of 69 +/- 8 nm and a diameter of 23 +/- 1 nm. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blots of purified hook preparations using the FlgE antiserum also revealed a polypeptide ladder, suggesting that the hooks are composed of a covalently cross-linked polypeptide. PMID- 8206842 TI - The Escherichia coli proU promoter element and its contribution to osmotically signaled transcription activation. AB - The proU operon of Escherichia coli encodes a high-affinity glycine betaine transport system which is osmotically inducible and enables the organism to recover from the deleterious effects of hyperosmotic shock. Regulation occurs at the transcriptional level. KMnO4 footprinting showed that the preponderance of transcription initiated at a single primary promoter region and that proU transcription activation did not occur differentially at alternate promoters in response to various levels of salt shock. Mutational analysis confirmed the location of the primary promoter and identified an extended -10 region required for promoter activity. Specific nucleotides within the spacer, between position 10 and position -35, were important for maximal expression, but every mutant which retained transcriptional activity remained responsive to osmotic signals. A chromosomal 90-bp minimal promoter fragment fused to lacZ was not significantly osmotically inducible. However, transcription from this fragment was resistant to inhibition by salt shock. A mutation in osmZ, which encodes the DNA-binding protein H-NS, derepressed wild-type proU expression by sevenfold but did not alter expression from the minimal promoter. The current data support a model in which the role of the proU promoter is to function efficiently at high ionic strength while other cis-acting elements receive and respond to the osmotic signal. PMID- 8206843 TI - Genetic complementation analysis of the Agrobacterium tumefaciens virB operon: virB2 through virB11 are essential virulence genes. AB - The Agrobacterium tumefaciens virB gene products are proposed to assemble into a transport system capable of exporting complexes of DNA and protein across the bacterial envelope en route to plant cells. Nonpolar null mutations were constructed in each of the 11 virB genes of the A. tumefaciens pTiA6NC plasmid. In tumorigenicity assays, delta virB1 mutants exhibited severely attenuated virulence and delta virB2 through delta virB11 mutants exhibited avirulence. NdeI restriction sites introduced at the predicted translational start sites of the virB genes were used to subclone each of the virB genes downstream of the lacZ or virB promoter on broad-host-range plasmids. virB gene expression plasmids were used to define promoter and general sequence requirements for genetic complementation of the deletion mutations. Whereas virB1 and virB2 complemented delta virB1 and delta virB2, respectively, only when expressed in trans from the virB promoter, virB3 through virB11 complemented the corresponding deletion mutations when expressed in trans from either the lacZ or virB promoter. Several virB genes required additional upstream or downstream sequences for complementation: (i) virB2 complemented the delta virB2 mutation only when the complementing plasmid coexpressed virB1 and virB2, (ii) virB6 and virB9 complemented the delta virB6 and delta virB9 mutations only when the complementing plasmids carried at most 55 and 230 bp of sequences residing 5' of these genes, respectively, and (iii) virB7 and virB8 complemented the delta virB7 and delta virB8 mutations only when the complementing plasmid coexpressed virB7 and virB8. These studies established that virB1 is an accessory virulence determinant and virB2 through virB11 are absolutely essential for the A. tumefaciens infection process. PMID- 8206844 TI - RecOR suppression of recF mutant phenotypes in Escherichia coli K-12. AB - The recF, recO, and recR genes form the recFOR epistasis group for DNA repair. recF mutants are sensitive to UV irradiation and fail to properly induce the SOS response. Using plasmid derivatives that overexpress combinations of the recO+ and recR+ genes, we tested the hypothesis that high-level expression of recO+ and recR+ (recOR) in vivo will indirectly suppress the recF mutant phenotypes mentioned above. We found that overexpression of just recR+ from the plasmid will partially suppress both phenotypes. Expression of the chromosomal recO+ gene is essential for the recR+ suppression. Hence we call this RecOR suppression of recF mutant phenotypes. RecOR suppression of SOS induction is more efficient with recO+ expression from a plasmid than with recO+ expression from the chromosome. This is not true for RecOR suppression of UV sensitivity (the two are equal). Comparison of RecOR suppression with the suppression caused by recA801 and recA803 shows that RecOR suppression of UV sensitivity is more effective than recA803 suppression and that RecOR suppression of UV sensitivity, like recA801 suppression, requires recJ+. We present a model that explains the data and proposes a function for the recFOR epistasis group in the induction of the SOS response and recombinational DNA repair. PMID- 8206845 TI - Stoichiometry of binding of CysB to the cysJIH, cysK, and cysP promoter regions of Salmonella typhimurium. AB - CysB is a member of the LysR family of transcriptional activators and regulates genes of the cysteine regulon in Salmonella typhimurium and Escherichia coli. CysB binds to specific sites just upstream of the -35 regions of the cysJIH, cysK, and cysP promoters, where, in the presence of N-acetyl-L-serine, it stimulates transcription initiation. The cysK and cysP promoters contain additional binding sites, and we have proposed that CysB bends these promoters by binding to adjacent sites. N-Acetyl-L-serine is thought to decrease the magnitude of such bending. Since stoichiometric data bearing on this model have been lacking, we analyzed complexes in gel mobility shift experiments with 35S-labeled CysB and 32P-labeled promoter fragments. CysB was found to bind as a tetramer, and N-acetyl-L-serine increased the electrophoretic mobilities of one-protein complexes of the multibinding site cysK and cysP promoters without changing their stoichiometry, indicating that a single CysB tetramer can bend these promoters and that N-acetyl-L-serine diminishes such bending. Bend angles for both promoters were calculated to be 100 and 50 degrees in the absence and presence of N-acetyl-L-serine. N-Acetyl-L-serine affected neither the stoichiometry nor the electrophoretic mobility of cysJIH promoter complexes, which are not known to contain bent DNA. DNA bending may be a mechanism for sequestering CysB at certain promoter sites by increasing their affinity for this protein in the absence of N acetyl-L-serine. PMID- 8206846 TI - Overproduction of the bacterial flagellar switch proteins and their interactions with the MS ring complex in vitro. AB - The flagellar switch proteins (FliG, FliM, and FliN) of Salmonella typhimurium were overproduced in Escherichia coli and partially purified in soluble form. They were mixed with purified MS ring complexes (which consist of subunits of FliF protein) to examine their interactions in vitro. The degree of interaction was estimated by ultracentrifugation, followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. From the band density on the gel, we estimated that FliG bound to the MS ring complex at an approximately 1:1 molar ratio (FliG:FliF), whereas FliM did so only at a 1:5 molar ratio (FliM:FliF). FliN did not bind to the MS ring complex by itself or in the presence of the other switch proteins. A possible configuration of the switch proteins is discussed. PMID- 8206847 TI - Introduction of new carotenoids into the bacterial photosynthetic apparatus by combining the carotenoid biosynthetic pathways of Erwinia herbicola and Rhodobacter sphaeroides. AB - Carotenoids have two major functions in bacterial photosynthesis, photoprotection and accessory light harvesting. The genes encoding many carotenoid biosynthetic pathways have now been mapped and cloned in several different species, and the availability of cloned genes which encode the biosynthesis of carotenoids not found in the photosynthetic genus Rhodobacter opens up the possibility of introducing a wider range of foreign carotenoids into the bacterial photosynthetic apparatus than would normally be available by producing mutants of the native biosynthetic pathway. For example, the crt genes from Erwinia herbicola, a gram-negative nonphotosynthetic bacterium which produces carotenoids in the sequence of phytoene, lycopene, beta-carotene, beta-cryptoxanthin, zeaxanthin, and zeaxanthin glucosides, are clustered within a 12.8-kb region and have been mapped and partially sequenced. In this paper, part of the E. herbicola crt cluster has been excised and expressed in various crt strains of Rhodobacter sphaeroides. This has produced light-harvesting complexes with a novel carotenoid composition, in which the foreign carotenoids such as beta-carotene function successfully in light harvesting. The outcome of the combination of the crt genes in R. sphaeroides with those from E. herbicola has, in some cases, resulted in an interesting rerouting of the expected biosynthetic sequence, which has also provided insights into how the various enzymes of the carotenoid biosynthetic pathway might interact. Clearly this approach has considerable potential for studies on the control and organization of carotenoid biosynthesis, as well as providing novel pigment-protein complexes for functional studies. PMID- 8206848 TI - The pyrimidine biosynthesis operon of the thermophile Bacillus caldolyticus includes genes for uracil phosphoribosyltransferase and uracil permease. AB - A 3-kb DNA segment of the Bacillus caldolyticus genome including the 5' end end of the pyr cluster has been cloned and sequenced. The sequence revealed the presence of two open reading frames, pyrR and pyrP, located immediately upstream of the previously sequenced pyrB gene encoding the pyrimidine biosynthesis enzyme aspartate transcarbamoylase. The pyrR and pyrP genes encoded polypeptides with calculated molecular masses of 19.9 and 45.2 kDa, respectively. Expression of these ORFs was confirmed by analysis of plasmid-encoded polypeptides in minicells. Sequence alignment and complementation analyses identified the pyrR gene product as a uracil phosphoribosyltransferase and the pyrP gene product as a membrane-bound uracil permease. By using promoter expression vectors, a 650-bp EcoRI-HincII fragment, including the 5' end of pyrR and its upstream region, was found to contain the pyr operon promoter. The transcriptional start point was located by primer extension at a position 153 bp upstream of the pyrR translation initiation codon, 7 bp 3' of a sequence resembling a sigma A-dependent Bacillus subtilis promoter. This established the following organization of the ten cistrons within the pyr operon: promoter-pyrR-pyrP-pyrB-pyrC-pyrAa-pyrA b-orf2 pyrD-pyrF-pyrE. The nucleotide sequences of the region upstream of pyrR and of the pyrR-pyrP and pyrP-pyrB intercistronic regions indicated that the transcript may form two mutually exclusive secondary structures within each of these regions. One of these structures resembled a rho-independent transcriptional terminator. The possible implication of these structures for pyrimidine regulation of the operon is discussed. PMID- 8206849 TI - Regulation of the Bacillus subtilis pyrimidine biosynthetic (pyr) gene cluster by an autogenous transcriptional attenuation mechanism. AB - A complete transcript of the Bacillus subtilis pyr operon contains the following elements in 5' to 3' order: a 151-nucleotide (nt) untranslated leader; pyrR, encoding a 20-kDa protein; a 173-nt intercistronic region; pyrP, encoding a 46 kDa protein; a 145-nt intercistronic region; and eight overlapping cistrons encoding all of the six enzymes for de novo pyrimidine biosynthesis. Transcription is controlled by the availability of pyrimidines via an attenuation mechanism. There are three transcription terminators within the operon, each of which is preceded by another stem-loop structure, the antiterminator, whose formation would prevent formation of the terminator stem-loop. These are located in the leader, the pyrR-pyrP intercistronic region, and the pyrP-pyrB intercistronic region. Northern (RNA) blot analysis has identified transcripts of lengths which coincide with termination at these proposed attenuation sites and whose relative abundances vary in the expected pyrimidine-dependent manner. Each antiterminator contains a 50-base conserved sequence in its promoter-proximal half. Various transcriptional fusions of the pyr promoter and surrounding sequences to promoterless reporter genes support an attenuation mechanism whereby when pyrimidines are abundant, the PyrR protein binds to the conserved sequence in the pyr mRNA and disrupts the antiterminator, permitting terminator hairpin formation and promoting transcription termination. Deletion of pyrR from the chromosome resulted in the constitutive, elevated expression of aspartate transcarbamylase, which is encoded by pyrB, the third gene in the operon. Complementation of an E. coli upp mutant, as well as direct enzymatic assay, has demonstrated that pyrR also confers uracil phosphoribosyltransferase activity. Analysis of pyrR and upp deletion mutants demonstrated that upp, not pyrR, encodes the quantitatively important uracil phosphoribosyltransferase activity. The pyrP gene probably encodes an integral membrane uracil permease. PMID- 8206850 TI - Characterization of the gene encoding the autotrophic ATP sulfurylase from the bacterial endosymbiont of the hydrothermal vent tubeworm Riftia pachyptila. AB - ATP sulfurylase is a key enzyme in the energy-generating sulfur oxidation pathways of many chemoautotrophic bacteria. The utilization of reduced sulfur compounds to fuel CO2 fixation by the still-uncultured bacterial endosymbionts provides the basis of nutrition in invertebrates, such as the tubeworm Riftia pachyptila, found at deep-sea hydrothermal vents. The symbiont-containing trophosome tissue contains high levels of ATP sulfurylase activity, facilitating the recent purification of the enzyme. The gene encoding the ATP sulfurylase from the Riftia symbiont (sopT) has now been cloned and sequenced by using the partial amino acid sequence of the purified protein. Characterization of the sopT gene has unequivocally shown its bacterial origin. This is the first ATP sulfurylase gene to be cloned and sequenced from a sulfur-oxidizing bacterium. The deduced amino acid sequence was compared to those of ATP sulfurylases reported from organisms which assimilate sulfate, resulting in the discovery that there is substantial homology with the Saccharomyces cerevisiae MET3 gene product but none with the products of the cysDN genes from Escherichia coli nor with the nodP and nodQ genes from Rhizobium meliloti. This and emerging evidence from other sources suggests that E. coli may be atypical, even among prokaryotic sulfate assimilators, in the enzyme it employs for adenosine 5'-phosphosulfate formation. The sopT gene probe also was shown to specifically identify chemoautotrophic bacteria which utilize ATP sulfurylase to oxidize sulfur compounds. PMID- 8206851 TI - Expression of high-affinity glucose transport protein Hxt2p of Saccharomyces cerevisiae is both repressed and induced by glucose and appears to be regulated posttranslationally. AB - Expression of putative high-affinity glucose transport protein Hxt2p of Saccharomyces cerevisiae was repressed 15- to 20-fold in high concentrations of glucose or fructose. S. cerevisiae with either the ssn6-delta 9 or the hxk2-delta 1::URA3 mutation, each of which relieves glucose repression, exhibited high Hxt2p expression in both 2.0% glucose (normally repressing) and 0.05% glucose (normally derepressing) while S. cerevisiae with the snf1-delta 10 mutation, which causes constitutive repression, did not detectably express Hxt2p in either glucose concentration. In addition to repressing at high concentrations, glucose or fructose is required for induction of Hxt2p expression. Hxt2p was not expressed by wild-type S. cerevisiae in media containing only ethanol or galactose as carbon and energy source but was expressed if glucose was added. An hxk2-delta 1::URA3 mutant did not detectably express Hxt2p in ethanol or galactose, but an ssn6-delta9 mutant did highly express Hxt2p in both carbon sources. Thus, simple relief of glucose repression as occurs with hxk2 null mutants is insufficient for high-level Hxt2p expression. Mutation of ssn6, a general transcriptional repressor, does lead to Hxt2p expression in the absence of glucose induction, suggesting relief of an additional negative regulatory system. High expression of Hxt2p does not always result in HXT2-dependent high-affinity transport, implying that Hxt2p activity is regulated posttranslationally. In the high glucose condition for the ssn6 mutant, high-affinity glucose transport is derepressed. Deletion of the HXT2 locus does not diminish this level of transport. However, high-affinity glucose transport is diminished in the ssn6-delta9 hxt2 delta1 double mutant compared with ssn6-delta9 alone in low glucose. Thus, while constitutively expressed in ssn6 mutants, Hxt2p only appears to be active as a transporter under low-glucose conditions. Similarly, Hxt2p was found to be expressed under low-glucose conditions in an snf3 mutant which does not display high-affinity uptake. This finding suggests that SNF3 may be involved in the posttranslational regulation of Hxt2p. PMID- 8206852 TI - Growth phase variation of integration host factor level in Escherichia coli. AB - We have measured the intracellular abundance of integration host factor (IHF), a site-specific, heterodimeric DNA-binding protein, in exponential- and stationary phase cultures of Escherichia coli K-12. Western immunoblot analysis showed that cultures that had been growing exponentially for several generations contained 0.5 to 1.0 ng of IHF subunits per microgram of total protein and that this increased to 5 to 6 ng/microgram in late-stationary-phase cultures. IHF is about one-third to one-half as abundant in exponentially growing cells as HU, a structurally related protein that binds DNA with little or no site specificity. Wild-type IHF is metabolically stable, but deletion mutations that eliminated one subunit reduced the abundance of the other when cells enter stationary phase. We attribute this reduction to the loss of stabilizing interactions between subunits. A mutation that inactivates IHF function but not subunit interaction increased IHF abundance, consistent with results of previous work showing that IHF synthesis is negatively autoregulated. We estimate that steady-state exponential-phase cultures contain about 8,500 to 17,000 IHF dimers per cell, a surprisingly large number for a site-specific DNA-binding protein with a limited number of specific sites. Nevertheless, small reductions in IHF abundance had significant effects on several IHF-dependent functions, suggesting that the wild type exponential phase level is not in large excess of the minimum required for occupancy of physiologically important IHF-binding sites. PMID- 8206853 TI - A novel toluene-3-monooxygenase pathway cloned from Pseudomonas pickettii PKO1. AB - Plasmid pRO1957, which contains a 26.5-kb fragment from the chromosome of Pseudomonas pickettii PKO1, allows P. aeruginosa PAO1 to grow on toluene or benzene as a sole carbon and energy source. A subclone of pRO1957, designated pRO1966, when present in P. aeruginosa PAO1 grown in lactate-toluene medium, accumulates m-cresol in the medium, indicating that m-cresol is an intermediate of toluene catabolism. Moreover, incubation of such cells in the presence of 18O2 followed by gas chromatography-mass spectrometry analysis of m-cresol extracts showed that the oxygen in m-cresol was derived from molecular oxygen. Accordingly, this suggests that toluene-3-monooxygenation is the first step in the degradative pathway. Toluene-3-monooxygenase activity is positively regulated from a locus designated tbuT. Induction of the toluene-3-monooxygenase is mediated by either toluene, benzene, ethylbenzene, or m-cresol. Moreover, toluene 3-monooxygenase activity induced by these effectors also metabolizes benzene and ethylbenzene to phenol and 3-ethylphenol, respectively, and also after induction, o-xylene, m-xylene, and p-xylene are metabolized to 3,4-dimethylphenol, 2,4 dimethylphenol, and 2,5-dimethylphenol, respectively, although the xylene substrates are not effectors. Styrene and phenylacetylene are transformed into more polar products. PMID- 8206854 TI - Topological promoter coupling in Escherichia coli: delta topA-dependent activation of the leu-500 promoter on a plasmid. AB - The leu-500 promoter of Salmonella typhimurium is activated in topA mutants. We have previously shown that this promoter can be activated on circular plasmids in a manner that depends on transcription and translation of the tetracycline resistance gene tetA and insertion of its product into the cell membrane. We have suggested that in the absence of enzymatic relaxation by topoisomerase I, the local domain of transcription-induced DNA supercoiling reaches a steady-state level that leads to the activation of the leu-500 promoter. In the present paper, we have shown that the leu-500 promoter may also be activated in Escherichia coli. Comparison of the closely related pair of E. coli strains DM800 (delta topA) and SD108 (topA+) shows that the activation is dependent on the presence of a null mutation in topA. We have also shown that activation of the plasmid-borne leu-500 promoter depends, as in S. typhimurium, on the function of an adjacent tetA gene, suggesting that membrane anchorage of the TetA peptide prevents dissipation of transcription-induced supercoiling by superhelical diffusion. The activity of the leu-500 promoter is boosted by placing a divergent tac promoter on the side opposite to tetA. The topoisomer distributions of these plasmids extracted from the cell have been analyzed. We find that when the parent plasmid pLEU500Tc, containing the leu-500 promoter upstream of the complete tetA gene, is extracted from E. coli DM800 (delta topA), the distribution of linking numbers is bimodal. There is a fraction with a lower level of supercoiling (mean linking difference approximately -0.05) that is constant for all plasmids extracted from either delta topA or topA+ cells. In addition, we observe a second fraction with highly negatively supercoiled DNA (mean linking difference approximately -0.09) only in DNA extracted from delta topA cells. The proportion of the oversupercoiled fraction correlates with the activity of the leu-500 promoter: it is strongly reduced when the tetA promoter is deleted or when translation of TetA is prematurely terminated, while it is increased when the strong tac promoter is present in cis. We suggest that this oversupercoiled fraction represents the proportion of plasmid molecules active in tetA transcription and that it is this supercoiling that activates the leu-500 promoter. PMID- 8206855 TI - Regulation of Caulobacter crescentus ilvBN gene expression. AB - As part of an effort to determine the mechanisms employed by Caulobacter crescentus to regulate gene expression, the ilvBN genes encoding the two subunits of an acetohydroxy acid synthase (AHAS) have been characterized. Analysis of the DNA sequences indicated that the C. crescentus AHAS was highly homologous to AHAS isozymes from other organisms. S1 nuclease and primer extension studies demonstrated that transcription initiation occurred 172 bp upstream of the AHAS coding region. The region between the AHAS coding region and the transcription initiation site was shown to have the properties of a transcription attenuator. Deletion analysis of the region containing the stem-loop structure of the proposed attenuator resulted in the derepression of ilvBN expression. Thus, it appears that C. crescentus uses attenuation to regulate the expression of the ilvBN operon. PMID- 8206856 TI - The gene coding for polynucleotide phosphorylase in Photorhabdus sp. strain K122 is induced at low temperatures. AB - Photorhabdus sp. strain K122 was found to produce higher levels of the protein CAP87K when cultured at 9 degrees C than when cultured at 28 degrees C. NH2 terminal sequencing of this protein revealed homology with the NH2 terminus of Escherichia coli polynucleotide phosphorylase. A 4.5-kb DNA fragment from strain K122 was cloned and sequenced and found to have 75% identity to the E. coli rpsO pnp operon coding for ribosomal protein S15 and polynucleotide phosphorylase, respectively. Predicted proteins encoded by this sequence were found to have 86% identity with ribosomal protein S15 and polynucleotide phosphorylase from E. coli, and the genes were called rpsO and pnp, respectively. Quantitation of rpsO and pnp mRNA transcripts from K122 revealed that there was a 2.4-fold increase in the level of pnp mRNA and a 1.9-fold decrease in the level of rpsO mRNA at 9 degrees C relative to 28 degrees C. Primer extension analysis revealed the positions of possible promoters controlling the expression of rpsO and pnp in K122, suggesting that the genes are expressed independently. The increase in the level of pnp mRNA at 9 degrees C was not due to any relative increase in its stability compared with that of the rpsO transcript. However, there was evidence to suggest that it may be a result of a cold-inducible promoter, P2, in the intergenic region between rpsO and pnp. Several features of P2 support the suggestion that it may be cold inducible. PMID- 8206857 TI - The RNA polymerase of Chlamydia trachomatis has a flexible sequence requirement at the -10 and -35 boxes of its promoters. AB - Mutated variants of the predicted promoter of the countertranscript of the Chlamydia trachomatis plasmid were tested by in vitro transcription with chlamydial extract. A 3-bp deletion within the -10 region of the putative promoter caused the RNA polymerase to initiate transcription 3 bases downstream. Many single mutations in the -10 and -35 regions did not alter promoter function. However, some multiple mutations in both hexamers rendered the promoter inefficient or ineffective. Taken together, these results indicate that (i) the sequence requirement for chlamydial promoters differs from that for Escherichia coli and (ii) chlamydial RNA polymerase can tolerate considerably more variation at the -10 and -35 regions. These results are paradoxical considering the homology between C. trachomatis sigma 66 and E. coli sigma 70. PMID- 8206858 TI - The iron superoxide dismutase of Legionella pneumophila is essential for viability. AB - Legionella pneumophila, the causative agent of Legionnaires' disease, contains two superoxide dismutases (SODs), a cytoplasmic iron enzyme (FeSOD) and a periplasmic copper-zinc SOD. To study the role of the FeSOD in L. pneumophila, the cloned FeSOD gene (sodB) was inactivated with Tn903dIIlacZ, forming a sodB::lacZ gene fusion. By using this fusion, expression of sodB was shown to be unaffected by a variety of conditions, including several that influence sod expression in Escherichia coli: aeration, oxidants, the redox cycling compound paraquat, manipulation of iron levels in the medium, and the stage of growth. A reproducible twofold decrease in sodB expression was found during growth on agar medium containing charcoal, a potential scavenger of oxyradicals, in comparison with growth on the same medium without charcoal. No induction was seen during growth in human macrophages. Additional copies of sodB+ in trans increased resistance to paraquat. Construction of a sodB mutant was attempted by allelic exchange of the sodB::lacZ fusion with the chromosomal copy of sodB. The mutant could not be isolated, and the allelic exchange was possible only if wild-type sodB was present in trans. These results indicate that the periplasmic copper zinc SOD cannot replace the FeSOD. The data strongly suggest that sodB is an essential gene and that FeSOD is required for the viability of L. pneumophila. In contrast, Sod- mutants of E. coli and Streptococcus mutans grow aerobically and SOD is not required for viability in these species. PMID- 8206859 TI - Cloning and analysis of a gene cluster from Streptomyces coelicolor that causes accelerated aerial mycelium formation in Streptomyces lividans. AB - We describe the cloning and analysis of two overlapping DNA fragments from Streptomyces coelicolor that cause aerial mycelium to appear more rapidly than usual when introduced into Streptomyces lividans on a low-copy-number plasmid vector. Colonies of S. lividans TK64 harboring either clone produce visible aerial mycelia after only 48 h of growth, rather than the usual 72 to 96 h. From deletion and sequence analysis, this rapid aerial mycelium (Ram) phenotype appears to be due to a cluster of three genes that we have designated ramA, ramB, and ramR. Both ramA and ramB potentially encode 65-kDa proteins with homology to ATP-dependent membrane-translocating proteins. A chromosomal ramB disruption mutant of S. lividans was found to be severely defective in aerial mycelium formation. ramR could encode a 21-kDa protein with significant homology to the UhpA subset of bacterial two-component response regulator proteins. The overall organization and potential proteins encoded by the cloned DNA suggest that this is the S. coelicolor homolog of the amf gene cluster that has been shown to be important for aerial mycelium formation in Streptomyces griseus. However, despite the fact that the two regions probably have identical functions, there is relatively poor homology between the two gene clusters at the DNA sequence level. PMID- 8206860 TI - Activation of spo0A transcription by sigma H is necessary for sporulation but not for competence in Bacillus subtilis. AB - spo0A and spo0H are needed for the initiation of sporulation and for the development of genetic competence in Bacillus subtilis. Transcription of spo0A initiates from two promoters, Pv and Ps. Pv is active during vegetative growth and is recognized by RNA polymerase containing sigma A. Expression from Ps increases during sporulation and depends on sigma H, the spo0H gene product. A deletion mutation, spo0A delta Ps, that removes the promoter controlled by sigma H blocked sporulation but had no detectable effect on competence. These results indicate that expression of spo0A from Ps is necessary for sporulation and that the requirement for spo0H in competence development is not due to its role in expression of spo0A. PMID- 8206861 TI - Rhicadhesin-mediated attachment and virulence of an Agrobacterium tumefaciens chvB mutant can be restored by growth in a highly osmotic medium. AB - Cyclic beta-1,2-glucan is considered to play a role in osmoadaptation of members of the family Rhizobiaceae in hypotonic media. Agrobacterium tumefaciens chvB mutants, lacking beta-1,2-glucan, exhibit a pleiotropic phenotype, including nonmotility, attachment deficiency, and avirulence. Here we report that by growth of chvB mutant cells in tryptone-yeast extract medium supplemented with 7 mM CaCl2 and 100 mM NaCl, the mutant cells become motile, attach to pea root hair tips, and are virulent on Kalanchoe leaves. Moreover, whereas chvB mutants grown in tryptone-yeast extract medium containing 7 mM CaCl2 do not produce active rhicadhesin, addition of 100 mM NaCl to this medium resulted in restoration of rhicadhesin activity. The presence of CaCl2 appeared to be required for attachment, virulence, and activity of rhicadhesin. The results support a role for cyclic beta-1,2-glucan in osmoadaptation and strengthen the notion that rhicadhesin is required for attachment and virulence of A. tumefaciens. PMID- 8206862 TI - Expression of a yeast intron-containing tRNA in the archaeon Haloferax volcanii. AB - Expression of the yeast tRNAPro(UGG) gene in Haloferax volcanii resulted in the production of a single stable transcript that had not undergone intron processing or processing of 5' and 3' flanking sequences. Mutation of the exon-intron boundary region of this RNA to produce a precursor RNA with the preferred halobacterial consensus exon-intron boundary structure did not restore intron processing. Processing of 5' and 3' flanking sequences was restored when the acceptor stem U6-U67 pair was changed to A6-U67. The significance of these results in defining the recognition requirements of tRNA maturation enzymes in the halophilic domain Archaea is discussed. PMID- 8206863 TI - Protozyme: emerging evidence in nature. AB - The VMA1 locus in Saccharomyces cerevisiae contains a nested genetic element, the VDE gene, and expresses two functional proteins. A single VMA1 translational product seems to catalyze a self protein splicing in which an internal domain is excised out to produce a site-specific DNA endonuclease and the N- and C-domains are ligated by a transpeptidation reaction to yield a catalytic subunit of the vacuolar ATPase. Accumulating evidence in the past few years suggests that the VMA1 locus encodes a protozyme (for protos en zyme) which has dual roles in life as a protean catalyst for self protein splicing and for self gene homing. Four protozymes that share a common mechanism in protein splicing have been found in four organisms covering three major phylogenic trees. PMID- 8206864 TI - Crystallization and preliminary X-ray diffraction studies of the alpha-amylase inhibitor coded 0.19 from wheat kernel. AB - The alpha-amylase inhibitor coded 0.19 (0.19AI) from wheat kernel is a dimeric protein which inactivates exogenous alpha-amylases. Crystals of 0.19AI were grown at room temperature and pH 7.0 from a protein solution with a low salt concentration. They were trigonal, belonged to space group P3(1) or P3(2), and had unit cell dimensions of a = b = 79.3 A and c = 60.8 A. The crystals diffract X-rays to at least 2.0 A resolution and are stable to X-ray beams. The asymmetric unit appears to contain two 0.19AI dimers. A potential heavy-atom derivative was prepared by soaking the crystal in a HgCl2 solution. PMID- 8206865 TI - Cell-adhesive activity and receptor-binding specificity of the laminin-derived YIGSR sequence grafted onto Staphylococcal protein A. AB - Laminin contains multiple oligopeptide motifs to promote cell adhesion and migration. One of these motifs is YIGSR within the B1 chain. We reconstituted the cell-adhesive activity of YIGSR motif by grafting it onto a truncated form of the Staphylococcal protein A (designated tSPA) via cassette mutagenesis. When coated on a polystyrene surface, the YIGSR-grafted tSPA (YIGSR-tSPA) promoted attachment and spreading of mouse melanoma and human rhabdomyosarcoma cells, but not of hamster fibroblasts. The cell-adhesive activity of YIGSR-tSPA was abolished by amino acid substitution or scrambling of the inserted YIGSR sequence. Divalent cations Mn2+ and Mg2+, but not Ca2+, promoted the cell adhesion to YIGSR-tSPA. Interestingly, the YIGSR-tSPA-mediated cell adhesion was barely inhibited by the linear peptide CDPGYIGSR-NH2, but was strongly inhibited by the cyclic peptide CDPGYIGSRC and another peptide PEILDVPST, which is a specific inhibitor for integrin alpha 4 beta 1. Among various anti-integrin antibodies, anti-alpha 4 and anti-beta 1 antibodies specifically inhibited the cell adhesion to YIGSR-tSPA. In support of these observations, adhesion of rhabdomyosarcoma cells to intact laminin was also partially inhibited by synthetic PEILDVPST peptide and anti alpha 4 antibody. These results, taken together, indicate that the YIGSR motif exerts its cell-adhesive activity through interaction with integrin alpha 4 beta 1. PMID- 8206866 TI - Effect of starving and refeeding on lipid metabolism in suncus. AB - We have previously reported that fatty liver is easily induced in a novel experimental animal, Suncus murinus (suncus) by withholding food, and that apolipoprotein B (apo B) is not actively synthesized in the liver. In the present paper we describe the effect of starving and refeeding on lipid and lipoprotein metabolism in suncus, in order to explore the mechanisms of induction of fatty liver by starving and of its improvement by refeeding. Starvation induced increase in triglyceride content and decrease in glycogen content of the liver. Although the glycogen content returned to the level before starvation at 12 h after refeeding, the triglyceride content decreased gradually but did not reach the prestarvation level even at 24 h after refeeding in suncus. Plasma lipids, glucose, and insulin levels were decreased by starvation and returned to the levels before starvation between 8 and 24 h after refeeding. On the other hand, the plasma levels of free fatty acid and ketone bodies were elevated significantly by starvation and decreased rapidly by refeeding. These responses to starvation and refeeding, except for the change in hepatic triglyceride, are in common with other experimental animals, suggesting that there are no abnormalities in glucose metabolism or in fatty acid metabolism in suncus. In conclusion, the fatty liver induced by starvation in suncus may be caused by impaired triglyceride transport out of the liver, for which apolipoprotein B is mostly responsible, as reported previously. PMID- 8206868 TI - Specificity of sialyl-sugar chain mediated recognition by the hemagglutinin of human influenza B virus isolates. AB - Recognition specificity for sialylsugar chains by the hemagglutinin of influenza B viruses isolated in different years from 1940 through 1990 (B/Lee/40, B/Setagaya/3/56, B/Tokyo/7/66, B/Kagoshima/1/68, B/Gifu/2/73, B/Kanagawa/3/76, B/Ibaraki/2/85, B/Yamagata/16/88, and B/Bangkok/163/90) was studied using 13 gangliosides. Reactivity of the viruses' hemagglutinin binding to gangliosides was determined by using thin-layer chromatography/virus-binding assay, and also by measuring virus binding to erythrocytes modified by incubation with gangliosides in terms of the absorbance of hemoglobin released from the infected cells. Eight strains preferentially recognized a novel ganglioside, carrying lacto-series type I and II sugar chains with the Neu5Ac alpha 2-6Gal linkage. It was found that B/Gifu/2/73 strain binds to lacto-series gangliosides containing Neu5Ac alpha 2-6Gal and Neu5Ac alpha 2-3Gal linkages. Other gangliosides studied, including GM4, GM3(alpha 2-3), GM3(alpha 2-6), GM2, GM1a, GD3, GD1a, GD1b, and GT1b, were poor receptors. PMID- 8206867 TI - Molecular cloning and characterization of the rat cytochrome c oxidase subunit Vb gene. AB - We have isolated two non-overlapping clones containing the genes for subunit Vb of cytochrome c oxidase (COXVb) from a rat genomic library in Charon 4A using a newly isolated full-length cDNA as a probe. One of the two genomic clones, designated as lambda COXVb741, contained a functional gene (COXVb-1), while the other one, designated as lambda COXVb211, contained an intronless processed pseudogene (COXVb-2). The COXVb-1 gene spans approximately 1.8 kb and consists of four exons interrupted by three introns. The nucleotide sequences of all exons are completely identical to the corresponding sequences of the rat liver and brain COXVb cDNAs, indicating that this gene is actually expressed. The 5' flanking region of the gene lacks conventional TATA and CAAT boxes, but exhibits strong promoter activity in the chloramphenicol acetyltransferase (CAT) assay. Deletional analysis and gel shift assay of the 5'-flanking region suggested that the binding of nuclear factor Sp-1 could be essential for transcription of the gene. Southern blotting analysis implied the occurrence of multiple COXVb genes in the rat genome. However, the results of the present experiments suggest that only the COXVb-1 gene is expressed in rat tissues. PMID- 8206869 TI - Specific chemical cleavage of asparaginyl and glycyl-glycine bonds in peptides and proteins by anhydrous hydrazine vapor. AB - Hydrazinolysis of peptide or protein has been used for C-terminal amino acid determination by Akabori et al. (1952). In this study, proteins were reacted with anhydrous hydrazine vapor at 20 degrees C for 16 h. Asparaginyl linkages were cleaved. Asparagine and glutamine were converted to their hydrazides, beta hydrazidyl aspartic acid and gamma-hydrazidyl glutamic acid, respectively, even under milder conditions. The former hydrazide cyclizes to a 6-membered ring, asparaginyl bond at the carboxyl side. Other cleavages, including the glycyl glycine bond, were also observed. PMID- 8206870 TI - ATP-dependent uptake of anti-neoplastic agents by acidic organelles. AB - Daunomycin, an anti-neoplastic agent, is known to be sequestered by acidic organelles in normal and multidrug-resistant cells [Willingham, M.C., Cornwell, M.M., Cardarelli, C.O., Gottesman, M.M., & Pastan, I. (1986) Cancer Res. 46, 5941 5946]. We studied the mechanism of accumulation of daunomycin into acidic organelles using chromaffin granule vesicles and proteoliposomes reconstituted with purified F-type H(+)-ATPase as model systems. Radiolabeled daunomycin was taken up by chromaffin vesicles upon addition of ATP. Its ATP-dependent uptake was stimulated about 1.4- to 1.8-fold by valinomycin plus K+, but was inhibited by ammonium chloride (10 mM) and nigericin plus K+. Quinidine (5 microM), verapamil (5 microM), or vanadate (0.5 mM), inhibitors of P-glycoprotein, had no effect on its uptake. Daunomycin was also taken up by liposomes reconstituted with F-type H(+)-ATPase. Furthermore, doxorubicin and vinblastine were taken up by these vesicles, whereas colchicine and rhodamine 123 were not. The accumulations of daunomycin and doxorubicin in acidic organelles of cultured cells were decreased by inhibiting vacuolar ATPase by addition of bafilomycin A1 or concanamycin A, or by increasing the internal pH by addition of nigericin. Melittin and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide dissipated the delta pH and inhibited accumulation of daunomycin in the membrane vesicles and acidic organelles in cultured cells. These results indicate that the delta pH established by vacuolar-type ATPase drives the uptake of daunomycin, doxorubicin or vinblastine into acidic organelles, and that no specific transporters are involved in their uptakes. PMID- 8206871 TI - Changes in SH reactivity of the protein in porcine intestinal brush-border membranes associated with lipid peroxidation. AB - The effects of lipid peroxidation on the SH reactivity of the proteins in porcine intestinal brush-border membranes were examined using a fluorogenic thiol reagent, N-[7-dimethyl-amino-4-methylcoumarinyl]maleimide (DACM) in relation to lipid organization. Changes in the lipid organization were assessed by measurement of the rate of incorporation of 1,6-diphenyl-1,3,5-hexatriene (DPH) into the membrane lipids and the fluorescence anisotropy of DPH-labeled membranes. Treatment of the membranes with an oxygen-radical-generating system, i.e., ascorbic acid/Fe2+/tert-butyl hydroperoxide (t-BuOOH), resulted in decrease in the rate of DACM incorporation into the SH groups of the membrane proteins (DACM-labeling) and the amount of DACM labeled to the SH groups with a decrease in the lipid fluidity, depending on the formation of thiobarbituric acid-reactive substances and conjugated diene. Pretreatment of the membranes with diphenylamine effectively prevented the ascorbic acid/Fe2+/t-BuOOH-induced decreases in the DACM-labeling and DPH incorporation rates, whereas neither superoxide dismutase, catalase, sodium benzoate, nor mannitol showed a protective effect. The contribution of the lipid fluidity to the SH reactivity to DACM of the proteins in the membranes with different levels of lipid peroxidation was further examined using a lipid fluidizer, benzyl alcohol. The results showed that the DPH incorporation rate increased in proportion to increasing concentrations of the alcohol regardless of the peroxidation level of the membranes, whereas the susceptibility of the SH reactivity of the membrane proteins as to benzyl alcohol transitionally changed as the membranes were peroxidized to levels greater than 400 nmol conjugated diene/mg protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206872 TI - Phosphatidic acid induces the release of beta-glucuronidase but not lactoferrin from electropermeabilized human neutrophils. AB - We studied the degranulation reaction of electropermeabilized human neutrophils induced by 1,2-didecanoyl-3-sn-phosphatidic acid (PA10). PA10 dose-dependently induced the release of beta-glucuronidase, an enzyme of azurophil granules, but did not induce the release of lactoferrin, a protein of specific granules. The enzyme release by PA10 absolutely required Ca2+, ATP, and Mg2+ and the concentrations for the half-maximal response were 2.5 microM, 60 microM, and 0.25 mM, respectively. Although Ca2+ alone at concentrations higher than 10 microM induced the release of both beta-glucuronidase and lactoferrin, the extents of the release were far less than that of the beta-glucuronidase release by PA10. Phorbol myristate acetate (PMA) and 1-oleoyl-2-acetyl-sn-glycerol induced the release of lactoferrin alone at concentrations of Ca2+ below 0.5 microM while they induced the release of both beta-glucuronidase and lactoferrin at higher Ca2+ concentrations, indicating that the degranulation induced by PA10 is not mediated by diacylglycerol which might be formed from PA. The degranulation reactions induced by PA10 and PMA were dose-dependently inhibited by staurosporine and calphostin C, protein kinase C inhibitors, although no direct activation of protein kinase C by PA10 was observed. The extent of the beta glucuronidase release by PA10 was not enhanced by the addition of PMA. Propranolol, which inhibits protein kinase C as well as phosphatidic acid phosphohydrolase, strongly inhibited the degranulation reactions induced by PA10 and PMA. Ethanol, a metabolic modulator of phospholipase D, and cyclic AMP did not affect the degranulation reactions by PMA and PA10.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206873 TI - Programmed cell death in response to alkyllysophospholipids in endothelial cells. AB - Addition of the alkyllysophospholipid ET16-OMe, a putative antitumor drug, to the culture medium of human vascular endothelial cells resulted in apoptotic cell death. The death was characterized as programmed cell death since the process was inhibited by the addition of an inhibitor of protein synthesis. The mechanism responsible for apoptosis induced by alkyllysophospholipid has unique characteristics, as compared to those of apoptosis induced by other antitumor drugs, since the drug caused fragmentation of dying cells and its effect could be overcome by the presence of a survival factor, namely, fibroblast growth factor. PMID- 8206874 TI - Different distributions of glycosphingolipids in mouse and rabbit skeletal muscle demonstrated by biochemical and immunohistological analyses. AB - The expression of neutral glycosphingolipids and gangliosides was investigated in mouse and rabbit skeletal muscle by means of biochemical and immunochemical techniques. Neutral glycosphingolipids from muscle of the inbred rabbit strain used in this study showed a simple TLC pattern, comprising mainly monohexosylceramide. In addition to this compound, lactosylceramide, lacto-N neotetraosylceramide, globoside and Forssman GSL were detected in mouse muscle. The major ganglioside in both species was GM3; GM3 (Neu5Ac) and GM3(Neu5Gc) were found in a 3:1 ratio in mouse muscle, whereas the absence of GM3(Neu5Gc) is characteristic of rabbit muscle. As a general structural feature of all muscle GM3 gangliosides investigated, a C18 fatty acid and C18 sphingosine were the major components besides minor C22 and C24:1 fatty acids of the respective ceramide portions, as revealed by positive and negative ion FAB-MS. alpha 2-3 sialylated lacto-N-neotetraosyl-ceramide (sialylparagloboside) was expressed in both species, whereas the alpha 2-6 sialylated isomeric compound was found only in mouse muscle. Minute quantities of ganglio-series GM1, GD1a, GD1b, and GT1b were detected in muscles from both species. Glycosphingolipid expression could be confirmed immunohistochemically by examining transverse and longitudinal cryosections of skeletal muscle samples. The results provide the basis for the investigation of muscle specific glycosphingolipids that might modulate membrane protein functions in muscle. PMID- 8206875 TI - Interferon-gamma induces different subunit organizations and functional diversity of proteasomes. AB - To obtain information on the role of proteasomes in the immune system, we examined the effect of a major immunomodulatory cytokine, gamma interferon (IFN gamma), on the expressions, structures, and functions of proteasomes. IFN-gamma greatly increased the levels of the mRNAs encoding LMP2 and LMP7, putative immuno proteasome subunits encoded by genes within the class II MHC region, and these two subunits synthesized were assembled completely into the proteasomal multi subunit complex in various types of human cells. The subunit organization of proteasome changed in response to IFN-gamma stimulation, due to assembly of newly synthesized subunits through up- and down-expressions of at least 6 proteasome genes including LMP2/LMP7 without change in the structure of pre-existing proteasomes. Interestingly, IFN-gamma dramatically stimulated the trypsin-like and chymotrypsin-like activities of the multifunctional proteasome and depressed the peptidylglutamyl-peptide-hydrolyzing activity, without affecting the activity for ATP-, ubiquitin-dependent proteolysis. These results indicate that IFN-gamma modifies not only the structural organization of the proteasome, but also its functions. Based on these findings, we discuss the role in the antigen processing/presentation pathway of proteasomes with functional diversity acquired through alteration of their subunit assembly in response to IFN-gamma stimulation. PMID- 8206876 TI - Dynamic properties of nucleic acids in biosupramolecular systems, as studied by 31P NMR. AB - The dynamic properties of nucleic acids in five different types of intact supramolecular systems, namely, chicken erythrocyte chromatin, the wild type and a deletion mutant of the lambda phage, lipid-containing phage PM2, and Alteromonas espejiana ribosomes, were investigated by means of 31P solid-state NMR. The nucleic acids in the different supramolecular systems showed unique dynamic properties, which are closely connected with their functions. The total anisotropy of the phosphorus chemical shift (delta sigma = sigma 33-sigma 11) of the ribosomes was 210 ppm at 5 degrees C. This anisotropy was much larger than those of any DNA complexes, suggesting the highly rigid structure of ribosomal RNA. In contrast, 160 ppm was the largest chemical shift anisotropy at 5 degrees C for B-form DNA in the supramolecular systems. This flexibility would be essential for DNAs to exert their functions. The involvement of a condensation protein in the PM2 phage was supported by the chemical shift anisotropy. The spin lattice relaxation time in the proton rotating frame [T1 rho(H)] of the nucleic acids became shorter with the increase in the effective field in the rotating frame for all systems examined, showing that the motions of the nucleic acids effective for the relaxation are in the slow motional regime or in the range of omega 1 tau c = 1 at 5 degrees C. The motional state of DNA of the lambda phage was found to change at about 20 degrees C on the basis of the temperature dependence of the spin-lattice relaxation time of phosphorus (T1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206877 TI - Expression and characterization of human bone morphogenetic protein-2 in silkworm larvae infected with recombinant Bombyx mori nuclear polyhedrosis virus. AB - Recombinant human bone morphogenetic protein-2 (rhBMP-2) was expressed in silkworm larvae, and a milligram quantity of the protein was purified and characterized. The expressed rhBMP-2 was biologically active in terms of induction of alkaline phosphatase activity in MC3T3-E1 cells and ectopic bone formation in mice. On SDS-polyacrylamide gel electrophoretic analysis, the purified protein showed a 16 kDa band under reducing conditions and a 30 kDa band under non-reducing conditions. The silkworm-expressed rhBMP-2 was glycosylated and susceptible to endo-beta-N-acetylglucosaminidase F (endo F) and endo H, but resistant to endo D. Deglycosylated rhBMP-2 treated with endo F retained its biological activity. These results suggest that rhBMP-2 exists as a dimer and disulfide bond(s) are responsible for the dimerization. Moreover, sugar chains have no direct effect on the biological activity of the protein. The availability of a quite large amount of rhBMP-2 has allowed us to study the biological function of this interesting factor in detail. PMID- 8206878 TI - Transcription of the faoAB operon which encodes the HDT multienzyme complex involved in fatty acid beta-oxidation in Pseudomonas fragi B-0771. AB - Transcription of the two clustered genes, faoA and faoB, for the multienzyme complex for fatty acid beta-oxidation (HDT) from the Gram-negative bacterium, Pseudomonas fragi, was investigated. Northern blot hybridization and primer extension analysis indicated that these genes comprised an operon, giving a 3.6 kb mRNA. Transcription of the 3.6 kb faoAB mRNA was induced by palmitic acid. Using the lacZ gene as a reporter gene for a promoter activity search, the essential region for induction of the faoAB gene transcription by palmitic acid was mapped at the 331 bp region just upstream of the transcription initiation site. Deletion of the 136 bp SalI-NheI fragment just downstream of the transcription initiation site caused the constitutive expression of the faoA-lacZ fusion protein in P. fragi, suggesting that there is a regulatory element interacting with the transcription repressor. PMID- 8206879 TI - Novel isoforms of human cyclic AMP-responsive element modulator (hCREM) mRNA. AB - The cyclic AMP-response element (CRE), a transcriptional enhancer, is regulated by CREB (CRE-binding protein) which is the leucine zipper protein phosphorylated by protein kinase A in response to cAMP signal. The highly homologous protein CREM (CRE-modulator) is thought to modulate CREB-stimulated transcription, and is also involved in transcriptional control during spermatogenesis. In this paper, we report two types of cDNAs of human CREM (hCREM), type 1 and type 2; type 1 is a group of human counterparts of the mouse CREM alpha and type 2 is a novel form having a distinct 5' exon which is unrelated to any species of the CREB and CREM isoforms so far described. This unique 5' region of type 2 hCREM may suggest its independent expression from type 1 CREM. The specific 5' region of type 2 hCREM consisted of 88 bp, containing an initiation codon for translation, but no possible phosphorylation site, suggesting different roles from type 1 CREM. Both type 1 and 2 hCREMs are expressed in lymphoid and non-lymphoid cell lines. Their excess expression by transfection induced suppression of cAMP-mediated activation of transcription, suggesting their negative regulation of CRE-mediated transcription. PMID- 8206880 TI - Vasoactive intestinal peptide induces differentiation and MAP kinase activation in PC12h cells. AB - Vasoactive intestinal peptide (VIP), a neuropeptide coupled with adenylate cyclase, was found to induce neurite extension of PC12h cells. Neurites appeared within 1 h after addition of VIP and extended for at least 24 h. The half-maximal concentration for the effect of VIP was 50 nM. In addition to the morphological change, VIP induced expression of VGF protein, a neuron-specific protein associated with neuronal differentiation. Western blotting with anti phosphotyrosine antibody showed that VIP stimulated tyrosine phosphorylation of two proteins of 42 and 44 kDa, which may be two isoforms of MAP kinase, erk1 and erk2. Activation of MAP kinases was confirmed by ion-exchange chromatography on a Mono Q column, from which VIP-induced kinase activity was co-eluted with MAP kinase-immunoreactivity. Tyrosine-phosphorylation of MAP kinases was also stimulated by forskolin or dibutyryl cAMP, indicating that activation of MAP kinases by VIP might be mediated by cAMP. These results suggest that VIP-induced differentiation of PC12 cells is associated with cAMP-dependent activation of MAP kinases. PMID- 8206881 TI - Aspartate aminotransferase from a thermophilic formate-utilizing methanogen, Methanobacterium thermoformicicum strain SF-4: relation to serine and phosphoserine aminotransferases, but not to the aspartate aminotransferase family. AB - The primary structure of the aspartate aminotransferase (AspAT) of an archaebacterium, Methanobacterium thermoformicicum strain SF-4, has been determined by cloning and sequencing of the gene for the enzyme. The gene had a consensus promoter and a ribosome binding sequence of methanogens in the 5' untranslated region, followed by an open reading frame starting with ATG and terminating with TGA. The deduced amino acid sequence was identical with the partial amino acid sequences of the enzyme including the N-terminal sequence, and the deduced molecular weight of 41,684 was virtually identical to that reported earlier for this enzyme [Tanaka, T., Yamamoto, S., Taniguchi, M., Hayashi, H., Kuramitsu, S., Kagamiyama, H., & Oi, S. (1992) J. Biochem. 112, 811-815]. The gene was expressed in Escherichia coli by inserting it into an expression vector just downstream of the lacZ promoter, and this verified that the cloned gene really encodes the Methanobacterium AspAT. The primary structure of the Methanobacterium AspAT showed extremely low homology, 5%, with AspATs of eubacteria, eukaryotes, and a thermoacidophilic arachaebacterium, Sulfolobus solfataricus. On the other hand, the Methanobacterium AspAT showed remarkable amino acid sequence homology, 31.5%, with rat serine:pyruvate aminotransferase and, 13.5%, with E. coli phosphoserine aminotransferase. Thus, the Methanobacterium AspAT apparently belongs to subgroup IV of the aminotransferases [Mehta, P.K., Hale, T.I., & Christen, P. (1993) Eur. J. Biochem. 214, 549-561], but not to subgroup I, in which all the AspATs known so far are included. PMID- 8206882 TI - A new method for testing the functional dependence of unfolding free energy changes on denaturant concentration. AB - Denaturations of ribonuclease A, lysozyme, and cytochrome c by guanidine hydrochloride (GdnHCl), urea, and GdnHCl-urea mixture were studied at constant temperature and pH to assess the functional dependence of denaturational free energy change (delta GD) on denaturant concentration over an extended GdnHCl concentration range. Conventional analysis of GdnHCl-induced transition curve exhibits a linear plot of delta GD versus [GdnHCl] in the transition zone. To extend delta GD measurements beyond this narrow concentration range, GdnHCl induced unfolding was measured in the presence of different concentrations of urea. delta GD values from these measurements were corrected for the effect of urea on the free energy change using the appropriate relation. The corrected delta GD data were mapped onto the delta GD versus [GdnHCl] plot. For each protein, the dependence of free energy change on denaturation was found to be linear over the full GdnHCl concentration. PMID- 8206883 TI - Different mechanisms of regioselection of fatty acid hydroxylation by laurate (omega-1)-hydroxylating P450s, P450 2C2 and P450 2E1. AB - P450 2C2 as well as P450 2E1 [Fukuda, T. et al. (1993) J. Biochem. 113, 7-12] catalyzed the hydroxylation of medium chain fatty acids, although the regioselectivity of substrates of the former contrasted with that of the latter. Whereas P450 2E1 hydroxylated C9-C18 fatty acids at the omega-1 position and to a much lesser extent at the omega and omega-2 positions, P450 2C2 hydroxylated C9 C13 fatty acids at different positions dependent on the chain length of fatty acids. Among the fatty acids used as the substrate, undecanoate was hydroxylated at the omega-1 position almost exclusively by P450 2C2. The proportion of omega hydroxylated products produced by P450 2C2 was markedly increased with decreasing chain length of fatty acids, while the hydroxylation positions were enlarged to the omega-3 position with tridecanoate. When the conserved Thr at the putative distal helix was replaced with Ser, the substrate regioselectivity of the two P450s was affected in different manners. The mutation of P450 2C2 did not change the hydroxylation positions of C9-C12 fatty acids, but caused a significant decrease in the proportion of the omega-1 hydroxy analog in the total products. In sharp contrast to P450 2C2, the mutated P450 2E1 gave additional products to those with the wild-type P450, and the number of different products increased with increasing chain length of the fatty acids. Thus, the products of palmitate hydroxylation were identified as omega-1, omega-2, omega-3, omega-4, omega-5, omega-6, and omega-7 monohydroxy isomers using gas chromatography-electron impact mass spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8206884 TI - Polypeptide and carbohydrate structure of recombinant human interleukin-6 produced in Chinese hamster ovary cells. AB - A glycosylated form of human interleukin 6 (hIL-6) has been produced in Chinese hamster ovary (CHO) cells transfected with a cDNA clone for human IL-6. Recombinant hIL-6 was purified from a culture supernatant of the transfected CHO cells, and used for structural characterization. The complete amino acid sequence, composed of 185 amino acid residues, was determined and is identical to that predicted from the cDNA sequence. However, a recombinant hIL-6 species lacking two amino acid residues (Ala-Pro) from the N-terminus was also found. Two disulfide bonds are formed, between Cys45 and Cys51 and between Cys74 and Cys84. Recombinant hIL-6 carries one O-linked carbohydrate chain, and Thr139 is fully O glycosylated. A portion of recombinant hIL-6 protein carries one N-linked sialooligosaccharide chain, and the N-glycosylation occurs at Asn46. The structure of the N-linked sugar chains was estimated by a combination of sugar mapping and glycosidase digestion. The major structure of the N-linked sugar chain predicted was of a fucosylated biantennary or triantennary complex type. Fucosylated triantennary sugar chains with one or two N-acetyllactosaminyl repeats were also found. The structure of the O-linked sugar chain was determined by 500 mHz 1H-NMR to be NeuAc alpha 2-3Gal beta 1-3(NeuAc alpha 2-6) Gal-NAcol. PMID- 8206885 TI - Purification and characterization of the 1,200-kDa subfragment of connectin filaments produced by 0.1 mM calcium ions. AB - When myofibrils prepared from chicken leg muscle were treated with a solution containing 0.1 mM CaCl2 and 30 micrograms/ml of leupeptin, alpha-connectin, which exists as a longitudinal thin filament in a sarcomere, was split into beta connectin and a 1,200-kDa subfragment. The native subfragment was successfully purified without using any denaturant: It was extracted with 1 M KI solution from the Ca-treated myofibrils and purified by TSKgel G6000PW column chromatography. About 10 mg of the subfragment was yielded from 100 g of starting muscle. Using immunofluorescence microscopy and immunoelectron microscopy, we show here that polyclonal antibodies against the 1,200-kDa subfragment bind to the Z-disk and the epitope, which is about 0.34 micron apart from the Z-disk at a sarcomere length of 2.6 microns; the 1,200-kDa subfragment constitutes the proximal region of connectin filaments. Purified alpha-actinin decorated alpha-connectin and the 1,200-kDa subfragment on nitrocellulose blots of myofibrillar proteins separated by SDS-PAGE. Therefore, we conclude that connectin filaments are anchored to the Z-disk by the binding of the 1,200-kDa subfragment to alpha-actinin. PMID- 8206886 TI - A study on the metabolism of spermidine in mammals: purification and identification of a newly identified metabolite, 2-oxo-1-pyrrolidinepropionic acid, in rat urine. AB - In order to study the metabolism of spermidine in mammals, radioactive spermidine was injected intraperitoneally into a rat and urine was collected for analysis. Incorporation of radioactivity into putreanine, isoputreanine, spermidic acid, and N-aminopropylpyrrolidin-2-one was confirmed by ion-exchange chromatography, thin layer chromatography, and paper electrophoresis, the highest radioactivity being observed in the non-polar and acidic fraction of the collected urine. A radioactive compound was purified from the non-polar and acidic fraction, and identified as 2-oxo-1-pyrrolidinepropionic acid by comparison of its behavior on ion-exchange chromatography and thin layer chromatography with that of authentic 2-oxo-1-pyrrolidinepropionic acid, and recrystallization with the authentic compound. Acid hydrolysis of the radioactive compound produced radioactive spermidic acid, confirming the identification. To examine the interconversion between isoputreanine and N-aminopropylpyrrolidin-2-one, these compounds were deuterated and then intraperitoneally injected into a rat. Analysis of 24-h urine by gas-chromatography-mass-spectrometry indicated no interconversion between the two metabolites of spermidine under these conditions. An intracerebroventricular injection of radioactive spermidine into a rat showed that radioactivity was also incorporated into the metabolites of spermidine in the brain, and oxidative deamination of the aminopropyl moiety of spermidine was thought to be dominant in the central nervous system and vice versa in peripheral organs. PMID- 8206887 TI - A hydrophilic tetrahydro-beta-carboline in human urine. AB - A substance that exhibited a tryptophan-like fluorescence peak at 354 nm on excitation at 295 nm at neutral pH was isolated from human urine. This compound was determined by visible-light absorption spectroscopy, fluorescence spectroscopy, 1H and 13C NMR spectroscopies, and FAB-MS to be 1-(1',2',3',4',5' pentahydroxypentyl)-1,2,3,4-tetrahydro-2-carboli ne-3- carboxylic acid. This compound, named tetrahydropentoxyline, is a new type of hydrophilic tetrahydro beta-carboline, and its elution position was between those of 4-pyridoxic acid and kynurenic acid on C18 reversed-phase HPLC. The amount of tetrahydropentoxyline excreted in the urine of normal subjects [n = 21; age, 45 (SD 20) years] was about 5.2 (SD 1.0) mg per day. PMID- 8206888 TI - Amino acid sequence of calmodulin from wheat germ. PMID- 8206889 TI - The serpin superfamily of proteinase inhibitors: structure, function, and regulation. PMID- 8206890 TI - Isolation of active recombinant XPG protein, a human DNA repair endonuclease. AB - Complementation group G of xeroderma pigmentosum (XP-G) is one of the most rare and phenotypically heterogeneous forms of this inherited disorder. XP-G patients vary from having a very mild defect in DNA repair to being severely affected, and a few cases are also associated with the neurological complications of Cockayne's syndrome. The XPG gene encodes an acidic protein with a predicted molecular mass of 133 kDa that confers normal UV resistance when expressed in XP-G cells. Here we report the isolation of full-length XPG as a soluble protein expressed from a recombinant baculovirus. The purified polypeptide corrects the DNA nucleotide excision repair defect of XP-G cell extracts in vitro, and it acts as a magnesium dependent single-stranded DNA endonuclease. This is the first direct evidence for a human protein with properties that implicate it in the incision step of nucleotide excision repair. PMID- 8206891 TI - Activation of human factor V by meizothrombin. AB - A recombinant human prothrombin was prepared in which Arg155 was replaced by Ala. The recombinant prothrombin was converted into a meizothrombin derivative (R155A meizothrombin) that was resistant to autocatalytic removal of the fragment 1 domain. R155A meizothrombin appeared to be a potent factor V activator in reaction mixtures that contained negatively charged phospholipid vesicles. Factor V activation by R155A meizothrombin was characterized by second-order rate constants of 0.06 x 10(6) M-1 S-1 in the absence of phospholipid and 18 x 10(6) M 1 S-1 in the presence of 60 microM phospholipid vesicles composed of a 10:90 mol/mol mixture of phosphatidylserine (PS) and phosphatidylcholine (PC). The rate constant for thrombin-catalyzed activation of factor V was hardly affected by the presence of phospholipid vesicles and was 4.0 x 10(6) M-1 S-1. The initial rate of activation of 3 nM factor V by R155A meizothrombin was a function of the concentration of PS/PC vesicles present in the reaction mixture, and the calculated rate constant reached a plateau value at > or = 50 microM PS/PC. Gel electrophoretic analysis of factor V activation showed that R155A meizothrombin and thrombin cleaved the susceptible peptide bonds in factor V at different rates. However, both activators finally generated a factor Va molecule composed of a heavy chain with an M(r) of 104,000 and a light chain doublet with M(r) values of 74,000 and 71,000. Since meizothrombin is one of the major reaction products formed during the initial phase of prothrombin activation, these findings are indicative of a significant contribution of meizothrombin to in vivo factor V activation. PMID- 8206892 TI - Absence of a Ku-like DNA end binding activity in the xrs double-strand DNA repair deficient mutant. AB - Double-strand DNA break repair is important in maintaining the genetic integrity of the genome. Using a mobility shift assay, we find that a protein, or complex of proteins, that is present in mammalian and yeast cells binds to the ends of double-strand DNA and renders the ends resistant to exonuclease digestion. Additionally, a mammalian DNA double-strand repair-deficient mutant, xrs, has no observable DNA end binding activity, while a revertant cell has wild-type activity. In addition, mobility supershift assays using monoclonal antibodies to the human Ku antigen (M(r) 70,000 subunit) reveal that one of the proteins of this end binding activity may be the Ku antigen or a protein with similar antigenic determinants. These observations suggest that this DNA end-binding protein may function in DNA repair. PMID- 8206893 TI - Delineation of discrete domains for substrate, cocaine, and tricyclic antidepressant interactions using chimeric dopamine-norepinephrine transporters. AB - Neurotransmitter transporters determine the intensity and duration of signal transduction by controlling the rapid removal of transmitter molecules from the synaptic cleft. The importance of their function is further reflected by the medical and social implications of compounds that inhibit their activity such as the antidepressants and cocaine. Molecular characterization of these transporters has revealed that they are members of a large family of membrane proteins with 12 putative transmembrane domains. However, little information exists as to whether discrete domains of these proteins mediate the various defined functions of these transporters. In this study, we constructed a series of chimeras between two structurally related but pharmacologically distinct transporters, the dopamine and norepinephrine transporters. The properties of these chimeric transporters suggest that distinct regions of these molecules determine these individual functions. Regions from the amino-terminal through the first five transmembrane domains are likely to be involved in the uptake mechanisms and ionic dependence. Regions within transmembrane domains 6-8 determine tricyclic antidepressant binding and cocaine interactions, whereas the carboxyl-terminal region encompassing transmembrane domain 9 through the COOH-terminal tail appears to be responsible for the stereoselectivity and high affinity for substrates. The dissociation of the substrate uptake and cocaine binding properties of these transporters further raises the possibility that antagonists of cocaine action devoid of uptake blockade activity might be developed for the clinical management of cocaine addiction. PMID- 8206894 TI - Plasminogen mutants activated by thrombin. Potential thrombus-selective thrombolytic agents. AB - Plasmin, the enzyme responsible for degradation of fibrin in blood clots and thus thrombolysis, is normally formed when its zymogen plasminogen is activated by cleavage of the Arg561-Val562 bond by specific plasminogen activators. We have altered the activation characteristics of plasminogen by substituting the P3, P2, and P1' cleavage site residues with sequences from thrombin-cleavable proteins to produce a novel thrombolytic agent which instead is activated by the blood clotting system. Plasminogen variants with thrombin cleavage sites from fibrinogen, the thrombin receptor, factor XIII, and factor XI were cleaved by thrombin with times to 50% cleavage of 28 h, 2.5 h, 5.7 min, and 3 min, respectively. In vitro clot lysis studies have shown that a variant in which the P3-P1' residues of plasminogen were substituted by the P7-P1' residues (Thr363 Ile370) from factor XI (T51) was sufficiently rapidly cleaved by thrombin to be activated by the endogenous thrombin produced by the coagulation cascade, resulting in rapid clot dissolution. Thrombin-activatable plasminogen therefore has the capacity to short circuit the physiological hemostatic mechanisms and produce fibrinolytic activity localized to the site of thrombin formation, that is, at the thrombus itself. The novel activation mechanism combined with the natural long circulating half-life of plasminogen gives this type of thrombolytic agent the potential for thrombus-selective plasmin generation and an extended duration of action. PMID- 8206895 TI - Nuclear hyperfine coupling of nitrogen in the coordination sphere of the diiron center of methane monooxygenase hydroxylase. AB - Electron spin echo envelope modulation spectroscopy identified two ligand 14N interactions with the mixed-valence, Fe(II/III) diiron center of methane monooxygenase hydroxylase from Methylococcus capsulatus (Bath). Characteristic features of the spectra obtained at 9 and 10 GHz were analyzed and fit by simulation. One of the nitrogens possessed superhyperfine parameters (Aiso = 0.8 MHz, reff = 3.2 A, e2Qq = 1.8 MHz, eta = 0.35) consistent with a non-coordinating amino nitrogen of a histidine imidazole ligand to a Fe(III). The second, more strongly interacting nitrogen (Aiso = 5.0 MHz, reff = 2.2 A, e2Qq = 3.0 MHz, eta = 0.3) corresponds to the N delta directly bound to the effective Fe(II). These findings extend the previous electron nuclear double resonance results on the Methylosinus trichosporium hydroxylase (Hendrich, M.P., Fox, B.G., Andersson, K.K., Debrunner, P.G., and Lipscomb, J.D. (1992) J. Biol. Chem. 267, 261-269), which identified the N delta-Fe(II) interaction but failed to quantify its magnitude. Measurement of the linear electric field g shift of this mixed-valence species indicated that the site is charge-polarized on to one of the iron atoms, and its symmetry suggests that either charge is shifted away from the Fe-Fe axis (if gmax is defined by the Fe-Fe axis) or that gmid and gmax are perpendicular to the Fe-Fe axis (charge strongly localized at Fe(III) and axis taken as gmin). PMID- 8206896 TI - Reduction of 3'-azido-3'-deoxythymidine (AZT) and AZT nucleotides by thiols. Kinetics and product identification. AB - 3'-Azido-3'-deoxythymidine (AZT), AZT 5'-monophosphate, and AZT 5'-triphosphate (AZTTP) were reduced by dithiothreitol with second-order rate constants of 2.30 x 10(-3), 1.50 x 10(-3), and 7.46 x 10(-4) M-1 s-1, respectively. Handlon and Oppenheimer reported that AZT is quantitatively reduced by thiols to 3'-amino-3' deoxythymidine (Handlon, A. L., and Oppenheimer, N. J. (1988) Pharm. Res. (N.Y.) 5, 297-299). In the present report, multiple products of this reaction were identified by the techniques of UV spectroscopy, phosphate analysis, coelution with authentic standards from reversed-phase high pressure liquid chromatography, two-dimensional NMR spectroscopy, and mass spectrometry. The product mixture from reduction of AZT 5'-monophosphate at pH 7.1 and 25 degrees C was composed of 2,3' anhydro-beta-D-threo-thymidine 5'-monophosphate (6.4%), 3'-amino-3' deoxythymidine 5'-monophosphate (19.6%), beta-D-threo-thymidine 5'-monophosphate (6.8%), thymine and 3-amino-2,3-dideoxyribal 5-monophosphate (8.9%), beta-D-threo thymidine 3',5'-cyclic monophosphate (9.1%), 3'-deoxy-2',3'-didehydrothymidine 5' monophosphate (31.5%), and 3',5'-anhydro-beta-D-threo-thymidine (17.8%). Thymine and 3',5'-anhydro-beta-D-threo-thymidine were also products of reduction of AZT and AZTTP. Furthermore, the nucleosides of the above monophosphates were products of reduction of AZT, and the corresponding triphosphates were products of reduction of AZTTP. The product ratios were dependent on the level of phosphorylation of AZT and on the pH of the reaction. Mechanisms for formation of these products are proposed. PMID- 8206897 TI - Dynamin binds to SH3 domains of phospholipase C gamma and GRB-2. AB - Src homology 3 (SH3) domains are found in a variety of proteins that are involved in signal transduction or represent components of the cytoskeleton. These domains are thought to serve as modules that mediate specific protein-protein interactions that include proline-rich sequences on the target protein. We have identified proteins of 110, 80, 65, and 43 kDa in human embryonic fibroblasts that bind specifically to the SH3 domain of phospholipase C gamma, a primary substrate of receptor tyrosine kinases, and characterized the 110-kDa band as the microtubule-activated GTPase dynamin. In addition, dynamin binds the son of sevenless adaptor protein GRB-2 with even higher affinity. This interaction does not require the dynamin GTPase function and involves a proline-rich target sequence between residues 812 and 820 of dynamin. PMID- 8206898 TI - The ATP-induced change of tryptophan fluorescence reflects a conformational change upon formation of ADP-sensitive phosphoenzyme in the sarcoplasmic reticulum Ca(2+)-ATPase. Stopped-flow spectrofluorometry and continuous flow rapid quenching method. AB - The ATP-induced change in the tryptophan fluorescence of the Ca(2+)-ATPase was determined with sarcoplasmic reticulum vesicles at pH 7.0 in the presence of Ca2+ under various conditions by steady-state measurements and stopped-flow spectrofluorometry. Formation of the phosphoenzyme intermediate was also determined by the continuous flow-rapid quenching method. The steady-state fluorescence at 0 degrees C decreased by 1.1% on addition of ATP, whereas no fluorescence change was induced by adenosine 5'-(beta,gamma methylene)triphosphate (a nonhydrolyzable ATP analog incapable of phosphorylating the enzyme). The time course of the ATP-induced fluorescence drop agreed well with that of the phosphoenzyme formation under all of the conditions tested, and the phosphoenzyme formed was largely sensitive to ADP. When phosphoenzyme isomerization from the ADP-sensitive form to the ADP-insensitive form was almost completely prevented by N-ethylmaleimide treatment, the time course of the ATP induced fluorescence drop again agreed with that of the phosphoenzyme formation. These results show that the ATP-induced fluorescence drop occurs upon formation of the ADP-sensitive phosphoenzyme. The results further indicate that the tryptophan fluorescence of this enzyme is insensitive to the conformational change which was previously shown (Suzuki, H., Obara, M., Kuwayama, H., and Kanazawa, T. (1987) J. Biol. Chem. 262, 15448-15456) to occur upon formation of the calcium-enzyme-substrate complex. Thus, we conclude that the ATP-induced drop in the tryptophan fluorescence reflects a conformational change occurring upon formation of the ADP-sensitive phosphoenzyme. PMID- 8206899 TI - Model of subunit composition of gamma-aminobutyric acid A receptor subtypes expressed in rat cerebellum with respect to their alpha and gamma/delta subunits. AB - Antibodies specific for subunits of the gamma-aminobutyric acid A (GABAA) receptor have been used to immunoprecipitate [3H]muscimol, [3H]Ro 15-4513, and [3H]Ro 15-1788 binding sites from deoxycholate-solubilized preparations of rat cerebellum. Of the antisera raised against alpha subunits, those specific for alpha 6 immunoprecipitated the largest proportion of receptors. Two populations of alpha 6-containing GABAA receptors were identified. The first was labeled with [3H]Ro 15-4513 and exhibited a pharmacological profile consistent with that observed for alpha 6 beta 2 gamma 2 in transfected cells (Luddens, H., Pritchett, D. B., Kohler, M., Killisch, I., Keinanen, K., Monyer, H., Sprengel, R., and Seeberg, P. H. (1990) Nature 346, 648-651). The second population was labeled only with [3H]muscimol and was deduced, from quantitative immunoprecipitation studies using combinations of antibodies, to contain both alpha 6 and delta subunits. The alpha 6 subunit was not observed to be present in combination with other alpha subunits or the gamma 1 subunit. Each of the other alpha subunits was found to be present in only one population of receptors in the cerebellum. Some subunits (alpha 4, alpha 5, and gamma 3) were not detectable. By combining information from quantitative immunoprecipitation experiments and Western blot analysis, a model describing the composition of all GABAA receptors in the cerebellum was constructed that defined the following alpha and gamma/delta combinations (percentage of cerebellar GABAA receptors): alpha 6 gamma 2 (36%), alpha 6 delta (23%), alpha 1 gamma 2 (28%), alpha 2 gamma 1 (8%), and alpha 3 gamma 2 (5%). PMID- 8206900 TI - Requirement for conformational flexibility in the signal sequence of precursor protein. AB - According to the "unlooping" model (de Vrije, T., Batenburg, A. M., Killian, J. A., and de Kruijff, B. (1990) Mol. Microbiol. 4, 143-150), proposed to explain how signal sequences serve to target proteins into the secretory pathway, the initial interaction of the signal sequence with the membrane in a helix-turn helix conformation (spanning half of the bilayer) plays an important role in the initiation of the translocation reaction. To test this model we have introduced 2 cysteines (at positions -5 and -19) in the signal sequence of the Escherichia coli outer membrane protein PhoE. The mutations did not influence the translocation of precursor PhoE in vivo or in vitro. The 2 cysteines were oxidized to form a disulfide bridge. In vitro translocation of the looped precursor into inner membrane vesicles was disturbed. The looped precursor competed with translocation of wild type precursor PhoE, and looped precursor that was first bound to inner membrane vesicles could be translocated after the addition of dithiothreitol. Apparently, the mutant precursor with a disulfide bridge in the signal sequence is arrested as a very early intermediate in the translocation process. All of these results are consistent with the proposed unlooping model and show that, besides the primary structure characteristics of a signal sequence, conformational flexibility is needed to initiate the translocation reaction. PMID- 8206901 TI - Expression of a dominant-negative mutant human insulin receptor in the muscle of transgenic mice. AB - To examine the in vivo effects of a kinase-deficient mutant human insulin receptor, we used the muscle creatine kinase promoter to express a putative dominant-negative receptor: Ala1134-->Thr (Moller, D. E., Yokota, A., White, M. F., Pazianos, A. G., and Flier, J. S. (1990) J. Biol. Chem. 265, 14979-14985) in transgenic mice. Two lines were generated, where receptor expression was restricted to striated muscle and was increased by 5-12-fold in skeletal muscle. Transgenic gluteal muscle insulin receptor kinase activity was reduced by approximately 80% after maximal in vitro insulin stimulation. Glycogen content in this muscle was reduced by 45% in transgenic mice. Insulin levels were approximately 2-fold higher, and glucose concentrations were 12% higher in transgenics fed ad libitum. Transgenic mice exhibited reduced in vivo sensitivity to low dose (0.1 milliunits/g) intravenous insulin. In isolated soleus muscles from transgenics, where mutant receptors were expressed at lower levels, insulin stimulated receptor kinase activity was reduced by 42%, but insulin-stimulated 2 deoxyglucose uptake was unaffected. These results indicate that (i) overexpression of a kinase-deficient human insulin receptor in muscle causes dominant-negative effects at the level of receptor kinase activation, (ii) impairment of insulin-stimulated muscle receptor tyrosine kinase activity can cause decreased insulin sensitivity in vivo, (iii) kinase-defective receptor mutants may be used to create novel animal models of tissue-specific insulin resistance. PMID- 8206902 TI - Thrombin receptor activation. Confirmation of the intramolecular tethered liganding hypothesis and discovery of an alternative intermolecular liganding mode. AB - Cleavage of the thrombin receptor's amino-terminal exodomain at the Arg41/Ser42 peptide bond within the sequence ... LDPR41/S42FLLRN ... is necessary and sufficient for receptor activation by proteases. The synthetic peptide SFLLRN activates the receptor independent of proteolysis. We proposed that the SFLLRN sequence is a tethered peptide ligand; receptor cleavage unmasks this agonist which then binds intramolecularly to effect receptor activation. The alternative hypothesis that receptor cleavage or exogenous SFLLRN effect receptor activation by disrupting tonic inhibitory interactions exerted by the receptor's amino terminal exodomain has not been excluded. We report that delta AMINO, a mutant thrombin receptor lacking the amino-terminal exodomain, was not constitutively active and responded to SFLLRN but not thrombin when expressed in Xenopus oocytes or mammalian cells. Thrombin signaling was restored when delta AMINO was co expressed with ATE-CD8 which encoded the receptor's amino-terminal exodomain fused to the transmembrane domain of CD8. Co-expression of a thrombin receptor lacking a functional tethered ligand domain ("F43A") with a non-signaling receptor mutant bearing an intact tethered ligand domain ("YYY") also reconstituted thrombin signaling. However, the EC50 for thrombin activation of cells co-expressing F43A and YYY was > 1000-fold that for cells expressing comparable levels of wild type receptor, while EC50s for activation by SFLLRN were similar. These and other data refute the release from inhibition hypothesis and suggest that while intermolecular liganding between two thrombin receptor molecules can occur, the intramolecular tethered liganding mechanism is the predominant mode of thrombin receptor activation. PMID- 8206903 TI - Uptake of non-transferrin-bound iron by both reductive and nonreductive processes is modulated by intracellular iron. AB - Non-transferrin-bound iron (NTBI) uptake occurs in a variety of cells by a saturable, specific and temperature-sensitive process. Our previous studies indicated that NTBI uptake by cardiac myocytes and Hep G2 cells was reversibly up regulated by iron deposition. In the present work we have characterized this up regulation and examined its mechanism by comparing the uptake of oxidized (Fe3+) and ascorbate-reduced (Fe2+) forms of iron. Iron loading markedly enhanced the uptake of iron both in the presence and absence of ascorbate, but the increment was greater when ascorbate was absent. This up-regulation is partially inhibited by actinomycin D and cycloheximide, indicating a requirement for protein synthesis. Uptake by the iron-loaded cells was less sensitive to thiol-alkylating agents and competing metal ions, but was more sensitive to proteolysis. Iron loading causes an increase in both Km and Vmax for uptake of both Fe2+ and Fe3+, although the values differ, suggesting distinct rate-limiting steps for uptake of Fe2+ and Fe3+. Consistent with this idea, uptake of the two ions showed differential sensitivity to thiol reagents, competing metal ions and monensin. The Fe(2+)-specific chelators bathophenanthroline disulfonate and ferrozine markedly inhibited iron uptake whether ascorbate was present or not, indicating that Fe3+ uptake is dependent on reduction to the ferrous state. This requirement for reduction was independent of the iron status of the cells, demonstrating that the process of up-regulation is not due to the appearance of a new mechanism for translocation of Fe3+ without reduction. Taken together, the evidence favors a model of NTBI transport where an obligate and rate-determining reduction of Fe3+ occurs prior to or during uptake, followed by translocation through an Fe2+ carrier. The distinct translocation mechanisms of uptake in the presence and absence of ascorbate suggest that exogenous Fe2+ does not access the carrier available to the nascent ferrous ion derived from the reductase and is consistent with close coupling between the reduction and the translocation processes. In iron-loaded cells with increased rates of NTBI transport, a similar mechanism prevails. PMID- 8206904 TI - Developmental and hormonal regulation of UDP-GlcNAc:dolichol phosphate GlcNAc-1-P transferase in mouse mammary gland. AB - The developmental and hormonal regulation of UDP-GlcNA:dolichol phosphate N acetylglucosamine-1-phosphate transferase (GPT), the enzyme which initiates the biosynthesis of asparagine-linked glycoproteins, was investigated in mouse mammary glands. An anti-peptide antibody raised against the carboxyl-terminal 11 amino acids of mouse GPT, immunoadsorbed GPT activity and recognized a protein of expected size (approximately 48 kDa) on Western blots. Mouse mammary glands at different stages of development were examined for GPT activity, immunoreactive protein, and GPT mRNA. All three parameters showed a similar trend, i.e. they were low in tissues from virgin and pregnant animals, increased steadily during lactation, reaching a peak around mid to late lactation, and declined thereafter in glands from post-lactating animals. At mid-lactation, the increase in GPT activity, immunoreactive protein, and GPT mRNA relative to the virgin stage was 9.5-, 3.3- and 5.4-fold respectively, on a per cell basis. These data suggest possible transcriptional and post-transcriptional modulation of GPT gene expression during development of mouse mammary gland. The results on hormonal regulation of GPT in mouse mammary explants and primary mouse mammary epithelial cells showed that all three parameters cited above were stimulated maximally by the combined presence of insulin, hydrocortisone, and prolactin, indicating that the hormonal regulation of GPT expression is also mediated at the level of RNA. PMID- 8206905 TI - Mutations at the stromal processing peptidase cleavage site of a thylakoid lumen protein precursor affect the rate of processing but not the fidelity. AB - Nuclear-encoded stromal proteins are imported into the chloroplast by means of presequences, or transit peptides, which are removed after import by a stromal processing peptidase (SPP); the presequences of thylakoid lumen proteins are processed by SPP at intermediate sites prior to transport of these proteins across the thylakoid membrane. SPP has been previously shown to be a highly specific enzyme, but the basis for the reaction specificity is unclear, because the cleavage sites of different substrates display virtually no primary structure similarity. We have examined the influence of the cleavage site residues on the SPP reaction mechanism by introducing mutations at these positions (denoted -1 and +1, relative to the SPP cleavage site) within the presequence of the lumenal 33-kDa photosystem II protein. Substitution of the -1 Arg by Ala or Met leads to a 5-7-fold reduction in the rate of processing, whereas substitution by Glu almost completely blocks cleavage. The replacement of the +1 Ala by Lys likewise almost completely blocks cleavage. None of the introduced -1 mutations affect cleavage fidelity; we show that all three mutants are cleaved only at the correct site. All of the mutant precursors are efficiently imported into the thylakoid lumen of intact chloroplasts, indicating that this cleavage event is not an important element of the overall import pathway. The results indicate that the identity of the -1 residue, within the context of a given presequence, is important in terms of influencing processing efficiency, but that the site of cleavage is specified by other determinants. At least a proportion of the other determinants are likely to be in close proximity to the cleavage site, since the deletion of a 7-residue section spanning this site completely blocks processing. PMID- 8206906 TI - Cytochrome P450IA1 is rapidly induced in normal human keratinocytes in the absence of xenobiotics. AB - Cytochrome P450IA1 is a polycyclic aromatic hydrocarbon (PAH)-responsive monooxygenase enzyme with no known endogenous inducer or substrate. We investigated the effect of suspension on P450IA1 gene (CYP1A1) expression in cultured human keratinocytes without the addition of xenobiotics. To prohibit adhesion and trigger differentiation, human keratinocytes or dermal fibroblasts were suspended in medium made semisolid with methylcellulose. Following suspension, we observed dramatic increases (> 100-fold) in steady state P450IA1 mRNA in keratinocytes within 1 h; however, dermal fibroblasts were nonresponsive. This effect was not dependent on methylcellulose itself and could be achieved by suspension in medium alone or in Percoll solution. The induction of P450IA1 mRNA was independent of exogenous calcium or serum concentrations, agents commonly used to signal differentiation. Adherent keratinocytes overlaid with methylcellulose exhibited slight morphological changes accompanied by increased P450IA1 mRNA. The activity of the P450IA1 enzyme was found to parallel Northern analysis data. Changes in keratinocyte adhesion or shape also affect other PAH responsive genes suggesting Ah receptor involvement. We report a novel mechanism for cell type-specific induction of CYP1A1 expression without the addition of xenobiotic inducers. These findings suggest a possible endogenous role for P450IA1 in stratified squamous epithelia. PMID- 8206907 TI - Structural requirements for interleukin-8 function identified by design of analogs and CXC chemokine hybrids. AB - Structure-activity relationships of human interleukin-8 (IL-8) were probed using chemically synthesized analogs with single or double amino acid substitutions, as well as hybrids derived by substituting IL-8 regions into IP10, a related protein that lacks IL-8 activity. The analogs were tested for functional activity by measuring induction of elastase release from human neutrophils and competition for binding of radiolabeled IL-8. The hybrid studies indicated that Gly31 and Pro32, as well as the NH2-terminal region from IL-8 are required to convert IP10 into a fully functional protein, suggesting that these elements are critical for IL-8 activity. Both disulfide bridges, linking residue 7 to 34 and residue 9 to 50, were critical for function, as shown by substituting the cysteine pairs with alpha-aminobutyric acid. Single conservative substitutions were generally accepted into the 10-22 region of IL-8, which contrasts with the ELR motif (residues 4-6), previously shown to be essential for activity. The importance of residues within the 10-15 region and the 17-22 region was demonstrated with hybrids. In addition, some of the 4-22 residues have structural roles that may be important; for example, Tyr13, Phe17, and Phe21 are involved in aromatic interactions in the IL-8 structure, and are also moderately sensitive to modification. Except for Cys50, the results argue against a role for the 36-72 region, including the COOH-terminal alpha-helix, in receptor binding. We conclude that the disulfide bridges and 30-35 turn provide a structural scaffold for the NH2-terminal region which includes the primary receptor-binding site (the ELR motif) and secondary binding and conformational determinants between residues 10 and 22. PMID- 8206908 TI - Direct binding of myosin II to phospholipid vesicles via tail regions and phosphorylation of the heavy chains by protein kinase C. AB - Recent cloning and sequencing studies suggest that heavy chains of all non-muscle myosins II have a protein kinase C (PKC) phosphorylation site within their tail regions. A fragment of human macrophage myosin heavy chain, encompassing its COOH terminal 396 amino acids (MIIAF46), was expressed in Escherichia coli to provide a model system for study of PKC-mediated phosphorylation. PKC phosphorylated this fragment when phosphatidylserine (PS) liposomes were present, but not when liposomes made from PS/phosphatidylcholine (PC) were used. The reaction required Ca2+, but not other activators such as diacylglycerol (DG) or phosphatidylinositol 4,5-bisphosphate. Phosphorylation of MIIAF46 was not observed in the presence of micelles of PS or PS/DG. Similar results were obtained using native myosin II purified from bovine brain and chicken intestine brush border. Phosphorylation of light chains, in contrast, occurred even with PS/PC liposomes if DG was present. Addition of the PS and PS/DG liposomes significantly increased the turbidities at 340 nm of MIIAF46 and native myosin II, and the extent of increase depended upon the type of myosin used. Also, PS and PS/DG liposomes shifted the gel filtration elution positions of MIIAF46 and myosin II. In contrast, liposomes of PS/PC and PS/PC/DG gave only a slight increase in turbidity with all myosins and fragments and did not noticeably shift their gel filtration elution positions. These results suggest that myosins II bind to PS liposomes via the COOH-terminal regions of their heavy chains with affinities specific to each myosin isoform, that the binding is dependent upon the PS composition, and that PKC phosphorylates the PS-bound heavy chains. PMID- 8206909 TI - Identification of the gene encoding lipoate-protein ligase A of Escherichia coli. Molecular cloning and characterization of the lplA gene and gene product. AB - R(+)-Lipoic acid is a cofactor required for function of the alpha-keto acid dehydrogenase and glycine cleavage enzyme complexes. The naturally occurring form of lipoate is attached by amide linkage to the epsilon-amino group of a specific lysine residue within conserved lipoate-accepting protein domains. Lipoate protein ligase(s) catalyze the formation of this amide bond between lipoyl groups and specific apoproteins. We report the isolation of the lplA gene which encodes an Escherichia coli lipoate-protein ligase. Strains with lplA null mutations transport lipoic acid normally but have severe defects in the incorporation and utilization of exogenously supplied lipoic acid and lipoic acid analogs. These strains are also highly resistant to selenolipoate (a growth-inhibiting lipoate analog) and contain no detectable lipoate-protein ligase activity in cell extracts. The lplA gene has been cloned, sequenced, and physically mapped to min 99.6 (4657 kilobases) of the E. coli chromosome. Upon overexpression, the 38-kDa lplA gene product was purified to homogeneity and shown to have a mass, N terminal sequence and amino acid composition consistent with the deduced 337 residue primary sequence. Enzyme assays show that purified LplA catalyzes the ATP dependent attachment of [35S]lipoic acid to apoprotein, thus confirming that lplA encodes lipoate-protein ligase A. Analysis of lplA null mutants also indicates the existence of a second (lplA-independent) lipoyl-ligase enzyme in E. coli. This is the first identification of a lipoate ligase gene and the first analysis of a purified lipoate ligase enzyme. PMID- 8206910 TI - Relationship of serine/threonine phosphorylation/dephosphorylation signaling to glucocorticoid regulation of tight junction permeability and ZO-1 distribution in nontransformed mammary epithelial cells. AB - The synthetic glucocorticoid dexamethasone regulates tight junction permeability resulting in an increased transepithelial electrical resistance (TER) of cultured 31EG4 mammary epithelial cells. Inhibition of cellular type 1 and type 2A protein phosphatase activity by okadaic acid reduced the TER of dexamethasone-treated monolayers of 31EG4 cells to basal levels within 24 h. Coincident with the increase in tight junction permeability, immunofluorescence revealed that okadaic acid caused a partial cellular redistribution of the ZO-1 tight junction associated protein. The potent glucocorticoid antagonist RU486 had no effect on TER or ZO-1 distribution, indicating that the effects of okadaic acid are not a result of disrupting glucocorticoid receptor function. Immunoprecipitation of 32P labeled cells and V8 protease peptide mapping demonstrated that dexamethasone did not alter ZO-1 phosphorylation. However, consistent with the changes in TER, dexamethasone induced a 2.3-fold stimulation in ZO-1 protein levels which was reduced to 73% of basal levels by okadaic acid. No effects on ZO-1 transcript levels were observed. Monolayers grown in the presence of glucocorticoids had only 28% less junction density and 16.5% more linear junction/cell, which cannot account for the observed increases of TER and ZO-1 protein levels. Taken together, our results have shown that a disruption of phosphorylation/dephosphorylation activity overrides the glucocorticoid regulation of tight junction permeability in 31EG4 mammary cells. PMID- 8206911 TI - Isolation of phosphorylated calmodulin from rat liver and identification of the in vivo phosphorylation sites. AB - A procedure is described for the isolation of calmodulin (CaM) from rat liver which produces a fraction containing non-phosphorylated, mono-, di-, and triphosphocalmodulin as determined by mass spectrometric analysis. The distribution of CaM between the various phospho-species varies from preparation to preparation even though the isolation procedure is rigidly defined, suggesting that CaM phosphorylation may be a very labile phenomenon dependent on the state of the liver as it is removed from the animal. Approximately 15% of CaM in the cell is phosphorylated. The in vivo phosphorylation sites were determined by mass spectrometric analysis of a combined CNBr and trypsin digestion of the phosphocalmodulin (phospho-CaM)-containing fractions. Phosphorylated peptides were sequenced using two mass scanning devices linked together for collisionally activated fragmentation studies to determine peptide sequences, and the phosphorylation sites were determined as Thr-79, Ser-81, and Ser-101. These correspond to three of the four in vitro target sites of calmodulin phosphorylation by casein kinase II, which indicates that this may be the enzyme responsible for the phosphorylation in vivo. A preliminary study on the modulatory activity of phosphorylated calmodulin using a sample extensively phosphorylated in vitro with casein kinase II confirmed that phospho-CaM has an altered biological activity, i.e. reduced activation of the erythrocyte plasma membrane Ca2+ pump. PMID- 8206912 TI - Influence of acceptor substrate primary amino acid sequence on the activity of human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase. Studies with the MUC1 tandem repeat. AB - Synthetic peptides (30 and 20 residues long) corresponding to the native MUC1 tandem repeat sequence (20 residues long) were glycosylated in vitro using UDP [3H]GalNAc and lysates from the human breast tumor cell line MCF7. Purified glycopeptides were sequenced on a gas-phase sequenator, and glycosylated positions were determined by measuring the incorporated radioactivity in fractions collected following each round of Edman degradation. The results showed that 2 of 3 threonines on the MUC1 tandem repeat peptides were glycosylated at the following positions: GVTSAPDTRPAPGSTAPPAH (underlined Thr residues indicate positions of GalNAc attachment); no glycosylation of serine residues was detected. Determination of the mass of the glycopeptides by mass spectrometry showed that a maximum of two molecules of GalNAc were covalently linked to each 20-residue repeat unit in the peptides. The influence of substrate primary amino acid sequence in determining the substrate specificity of UDP-N acetylgalactosamine:polypeptide N-acetylgalactosaminyl-transferase activity was evaluated using as acceptor substrates a series of overlapping 9-residue peptides that represent a moving set through the tandem repeat of the MUC1 mucin. In addition, the influence of primary amino acid sequence on acceptor substrate activity was evaluated using several peptides that contained single or double amino acid substitutions (relative to the native human MUC1 sequence). These included substitutions in the residues that were glycosylated and substitutions in the surrounding primary amino acid sequence. This study demonstrates that primary amino acid sequence, length, and relative position of the residue to be glycosylated dramatically affect the ability of peptides to serve as acceptor substrates for UDP-N-acetylgalactosamine:polypeptide N acetylgalactosaminyltransferase. PMID- 8206913 TI - Platelet-derived growth factor (PDGF) induction of egr-1 is independent of PDGF receptor autophosphorylation on tyrosine. AB - Autophosphorylation of the platelet-derived growth factor (PDGF) receptor on tyrosine, which is dependent upon and occurs immediately after ligand binding, has been linked to the activation of second messenger pathways thought to be necessary for the induction of gene expression, DNA synthesis, and mitogenesis. We have investigated PDGF signal transduction in Balb/c3T3 and NIH-3T3 cells at the level of immediate-early gene induction under three conditions in which PDGF receptor autophosphorylation in response to PDGF binding is blocked: cells transformed by v-rasKi, cells transformed by v-mos, and cells treated with genistein, a specific inhibitor of tyrosine kinases. PDGF induction of immediate early genes c-myc, c-fos, and JE is blocked in these systems. Induction of another immediate-early gene, egr-1, occurs normally despite the absence of measurable tyrosine kinase activity. The same results were obtained when cells were stimulated with PDGF-AA or PDGF-BB. It is not yet clear if this receptor tyrosine kinase-independent signal utilizes known PDGF second messengers, but these results demonstrate a new arm of the PDGF signal transduction pathway which operates in the absence of, and independently from, autophosphorylation of the receptor on tyrosine. PMID- 8206914 TI - Blue and red light reversibly control psbA expression in the cyanobacterium Synechococcus sp. strain PCC 7942. AB - The three psbA genes encoding the photosystem II D1 protein in Synechococcus sp. strain PCC 7942 respond differentially to an increase in intensity of white light through transcriptional induction of psbAII and psbAIII and accelerated degradation of psbAI and psbAIII messages. We report that the genes exhibit a novel photoreversible response involving blue and red light that is almost indistinguishable from the high-white light response. Transfer of cells from white to low-fluence blue light caused a decrease in the level of the psbAI message and increased levels of psbAII and psbAIII messages, whereas transfer to red or far-red light had little effect. Five min of blue light was sufficient to trigger psbAII and psbAIII induction; five min of subsequent red irradiation attenuated this response, whereas subsequent green or far-red light (or darkness) had no effect. Response to both high and blue light was insensitive to inhibitors of photosynthetic electron transport. We propose that Synechococcus modulates photosystem II biosynthesis in a variable light environment through a photoreception signal pathway, which is independent of photosystem II activity and which is distinct from red/green-reversible control of chromatically adapting cyanobacteria and the red/far-red-reversible phytochrome of plants. PMID- 8206915 TI - Band 3 Memphis variant II. Altered stilbene disulfonate binding and the Diego (Dia) blood group antigen are associated with the human erythrocyte band 3 mutation Pro854-->Leu. AB - Band 3 Memphis is a commonly occurring polymorphic form of the human red cell anion transporter (band 3, AE1). Band 3 Memphis migrates more slowly on an SDS polyacrylamide gel than normal band 3 and results from a point mutation Lys56- >Glu. Two types of band 3 Memphis, variants I and II, can be distinguished by their susceptibility to covalent labeling with H2DIDS (4,4'-diisothiocyanato-2,2' dihydrostilbene disulfonate). Memphis variant II is more readily labeled than Memphis variant I or normal band 3. The Memphis variant II is also associated with the presence of the Diego (Dia) blood group antigen on the red cells. We have shown that Memphis variant II carries the polymorphism Pro854-->Leu, as well as Lys56-->Glu. The blood group antigen (Dia) present at the surface of Memphis variant II type red cells suggests the mutation Pro854-->Leu causes a change in the structure of an extracellular loop of Memphis variant II band 3. We discuss possible ways in which the mutation Pro854-->Leu affects the reactivity of Lys539 to covalent reaction with H2DIDS. PMID- 8206916 TI - Importance of the loop connecting A and B helices of human interferon-gamma in recognition by interferon-gamma receptor. AB - Characterization of murine-human hybrid interferon-gamma (IFN-gamma) molecules suggests that substitution of the peptide connecting the A and B helices in human IFN-gamma with the murine sequence significantly blocks the protein's binding to the human interferon-gamma receptor. Mutagenesis showed that this effect is localized to the central part of this A-B loop peptide, particularly Ser20, Asp21, Val22, and Ala23. One mutant, IFN-gamma/A23E,D24E,N25K, was examined by NMR. This "EEK" mutation does not significantly alter the conformation of interferon-gamma, suggesting that the effects of these mutations are not the result of global conformational changes. The A-B loop is near histidine 111, a residue previously shown to be important in receptor-ligand interaction (Lunn, C. A., Fossetta, J., Dalgarno, D., Murgolo, N., Windsor, W., Zavodny, P. J., Narula, S. K., and Lundell, D. (1992) Protein Eng. 5, 253-257). We show that copper forms a complex between histidine 19 in the A-B loop and histidine 111. This metal complex lacks the ability to interact with the interferon-gamma receptor. These results suggest that the A-B loop contains important structural information needed for receptor-ligand binding and hence biological activity of human interferon-gamma. PMID- 8206917 TI - The importance of conserved nucleotides of 23 S ribosomal RNA and transfer RNA in ribosome catalyzed peptide bond formation. AB - We have constructed the double mutant G2252C/G2253C in Escherichia coli 23 S rRNA by site-directed mutagenesis. These phylogenetically conserved residues are protected from chemical modification by the 3' CCA terminus of the peptidyl-tRNA site (P site)-bound tRNA. Expression of C2252/C2253 23 S rRNA in E. coli severely compromises cell growth. Mutant rRNA is assembled into 50 S subunits and 70 S ribosomes but is discriminated against in polysomes. Mutant ribosomes function at lower rates in peptidyltransferase assays than wild type ribosomes. To test whether this defect derives from disruption of base pairing with the 2 cytidines of the invariant 3' CCA terminus of tRNA, a mutant E. coli tRNAPhe gene was constructed, with the CCA sequence changed to GGA. As deacylated species, mutant and wild type tRNAPhe inhibit peptidyl transfer identically. Mutant tRNAPhe was aminoacylated in vitro but failed to react as a P site substrate, with either mutant or wild type ribosomes. These results support a role for G2252 and G2253 of 23 S rRNA in peptidyltransferase function and a role for the 3' residues of peptidyl-tRNA in catalytically productive P site interaction; but they fail to provide evidence supporting canonical base pairing between these 23 S residues and the 3' end of peptidyl-tRNA. PMID- 8206918 TI - Conservation of regulated alternative splicing and identification of functional domains in vertebrate homologs to the Drosophila splicing regulator, suppressor of-white-apricot. AB - Although several splicing regulatory proteins have been identified in Drosophila through characterization of various genetic mutations, including sex-lethal, transformer, transformer-2, suppressor-of-white-apricot (su(wa)), and possibly suppressor-of-sable, none of these have been identified in vertebrates. We describe the cloning and characterization of human (HsSWAP) and mouse (MmSWAP) homologs of the su(wa) gene. Comparison of the Drosophila and mammalian proteins reveals five highly homologous regions, including an arginine/serine-rich domain and two repeated modules that are homologous to regions in the constitutive splicing factor, SPP91/PRP21. These modules thus define a new motif likely important in the regulatory and constitutive splicing functions of these proteins. The Drosophila su(wa) gene autoregulates its expression by control of splicing of its first two introns. Comparison of mammalian and Drosophila SWAP mRNAs revealed that the splice junctions of these regulated introns are precisely conserved, showing definitively that these genes are ancestrally related. Moreover, mammalian SWAP mRNAs are also alternatively spliced at the same splice sites, showing that mammalian SWAP expression is regulated (presumably autogenously) by control of splicing of these two introns. These several structural features therefore strongly suggest that the mammalian SWAP gene functions as a vertebrate alternative splicing regulator. PMID- 8206919 TI - Regulation of two E2F-related genes in presenescent and senescent human fibroblasts. AB - Several mammalian genes expressed in late G1 are positively regulated by E2F, a heterodimeric transcription factor. Genes encoding two E2F proteins, E2F-1 and DP 1, were regulated differently during the cell cycle and replicative senescence of normal human fibroblasts. In presenescent cells, E2F-1 mRNA was cell-cycle regulated, appearing a few hours before S phase. By contrast, DP-1 mRNA was constitutively expressed, independent of position in the cell cycle. After a finite number of divisions, normal cells enter a state of irreversible growth arrest termed senescence. Many genes remain mitogen-inducible in senescent cells; there are, however, exceptions, including several late G1 genes potentially regulated by E2F. Senescent cells expressed DP-1 at the presenescent level, but did not express E2F-1 mRNA. Senescent cells were also markedly deficient in E2F binding activity associated with the dihydrofolate reductase promoter. E2F-1 and DP-1 expression vectors only weakly induced DNA synthesis in quiescent or senescent human cells and immortal murine NIH3T3 cells, although the E2F-1 vector stimulated DNA synthesis in immortal murine A31 cells, and transactivated E2F responsive promoters in NIH3T3 cells. The results suggest that senescent cells may fail to express late G1 genes due to repression of E2F-1, leading to a deficiency of E2F activity. Furthermore, although E2F-1 stimulates DNA synthesis in some cells, other cells, including normal human fibroblasts, require additional factors. PMID- 8206920 TI - Short antisense oligonucleotide-mediated inhibition is strongly dependent on oligo length and concentration but almost independent of location of the target sequence. AB - The inhibitory effect of short antisense oligodeoxynucleotides (aODNs) on cRNA expression in Xenopus oocytes was measured using an electrophysiological assay based on subunit-specific block of cloned alpha-amino-3-hydroxy-5-methyl-4 isoxazole-propionate receptors. The effect of both phosphorothioate-modified (PS) and phosphodiester (PO) aODNs was strongly length dependent with a half-maximal inhibition calculated for an oligo length of 7.6 nucleotides (nt) and 9.9 nt, respectively. More than 95% inhibition was mediated by a PS aODN of 12 nt and by PO aODNs > or = 15 nt. At a given length PS and PO aODNs showed differential dependence of their inhibitory effect on the injected aODN concentration (half maximal inhibition at 18 ng/microliter for a PO 12-mer and at 0.19 ng/microliter for a PS 12-mer) and differential saturation behavior. The inhibitory effect of aODNs, even as short as 8 nt for PS oligomers, was highly sequence specific, but almost independent of the position of the respective target site on the cRNA (for PS 8-mers, > or = 70% expression inhibition throughout the tested target sites from the translation initiation to the 3'-untranslated region). Thus, short PS aODNs can be reliably used in order to specifically inhibit protein expression in experiments addressing physiological, molecular biological, and perhaps even therapeutical issues. PMID- 8206921 TI - In vivo targeting function of N-linked oligosaccharides with terminating galactose and N-acetylgalactosamine residues. AB - N-Linked biantennary, triantennary, and core fucosylated biantennary oligosaccharides were isolated from animal glycoproteins and derivatized at their reducing end with Boc-tyrosine. The terminal Gal residues were enzymatically removed and replaced with GalNAc. Tyrosinamide-oligosaccharides were radioiodinated and administered intravenously to mice. Pharmacokinetic and biodistribution studies revealed structure-dependent differences in the steady state volume of distribution, total body clearance rate, and targeting efficiency. Tyrosinamide-oligosaccharides were found to resist metabolism relative to a natural triantennary glycopeptide which was rapidly degraded in vivo. Triantennary oligosaccharides containing terminal Gal or Gal-NAc targeted the liver efficiently whereas biantennary oligosaccharides containing terminal Gal residues and differing only in their core fucosylation avoided recognition by the asialoglycoprotein receptor and were cleared unmetabolized by renal filtration. In contrast, biantennary oligosaccharides containing terminal Gal-NAc residues targeted the liver with much greater efficiency than Gal-terminated triantennary oligosaccharide. Core fucosylation reduced the metabolism rate of tyrosinamide-biantennary in the liver. The results establish the utility of tyrosinamide-oligosaccharides as probes to analyze the ligand specificity of mammalian lectins in vivo and demonstrate that a GalNAc-terminated biantennary is a potent ligand for the asialoglycoprotein receptor. PMID- 8206922 TI - Cloning, sequencing, and expression of Rhodococcus L-phenylalanine dehydrogenase. Sequence comparisons to amino-acid dehydrogenases. AB - L-Phenylalanine dehydrogenase catalyzes the NAD(+)-dependent, reversible, oxidative deamination of L-phenylalanine to form ammonia, phenyl pyruvate, and NADH. The enzyme has been purified to homogeneity from Rhodococcus sp. M4, and a partial amino acid sequence was obtained. A cosmid library of Rhodococcus sp. M4 genomic DNA was prepared and used to isolate a 2.5-kilobase PstI fragment that contained the pdh gene. The open reading frame of 1068 nucleotides encodes a polypeptide of 356 amino acids, portions of which match the amino acid sequence determined for the purified enzyme. Expression of the Rhodococcus pdh gene in Escherichia coli, which does not contain a phenylalanine dehydrogenase activity, yields a soluble enzyme exhibiting phenylalanine dehydrogenase activity. Both the enzyme purified from Rhodococcus and the enzyme expressed in E. coli are post translationally modified by removal of the amino-terminal methionine. The overall amino acid sequence is homologous to previously reported sequences of leucine and phenylalanine dehydrogenases as well as several glutamate dehydrogenases. The amino-terminal portion of the enzyme contains residues involved in L-amino acid binding and catalysis, while the carboxyl-terminal portion contains the presumptive dinucleotide-binding domain. A detailed sequence comparison of Rhodococcus phenylalanine dehydrogenase with leucine, phenylalanine, and glutamate dehydrogenases suggests residues involved in general amino acid binding and others that provide for amino acid discrimination. PMID- 8206923 TI - Substrate specificity of the two phosphate transport systems of Acinetobacter johnsonii 210A in relation to phosphate speciation in its aquatic environment. AB - In natural waters and domestic waste waters in which divalent metal ions are present in excess of Pi, H2PO4-, HPO4(2-), and MeHPO4 prevail at pH values physiological for Acinetobacter johnsonii 210A (pH 5.5-8.0). In view of the ability of this organism to extensively accumulate Pi and divalent cations in cytoplasmic polyphosphate granules, the substrate specificity of its two Pi transport systems was studied. The constitutive, proton motive force-driven Pi carrier, previously shown to be dependent on divalent cations, plays a major role in the divalent cation and Pi flux by translocating MeHPO4 rather than Pi. This notion is confirmed by the observation that divalent cations are cotransported with Pi in a 1:1 stoichiometry in proteoliposomes containing reconstituted Pi carrier protein. In contrast, the Pi repressible, periplasmic binding protein dependent Pi transport system mediates the uptake of H2PO4- and HPO4(2-). Pi uptake, but not MeHPO4 uptake, was stimulated in cells under Pi limitation, and the periplasmic Pi-binding protein has affinity for H2PO4- and HPO4(2-), but not for MeHPO4. When operating in concert, both systems enable A. johnsonii 210A to efficiently acquire Pi from its habitat through uptake of the predominant Pi species. PMID- 8206924 TI - Similarities between the primary structures of two distinct major surface proteins of Toxoplasma gondii. AB - Toxoplasma gondii possesses a 43-kDa surface protein (SAG3) that is expressed by all invasive stages. We have cloned and sequenced cDNAs encoding SAG3, with the longest one encoding a primary product of 385 amino acid residues. The deduced amino acid sequence contains a putative NH2-terminal signal sequence, as well as a glycosylphosphatidylinositol anchor attachment site. It is characterized by 12 cysteine residues whose distribution suggests a tandem duplication of a single ancestral motif containing 6 cysteine residues. Although no DNA sequence analogies were found, comparative amino acid sequence analysis detected a resemblance to SAG1, which is the major surface antigen specifically expressed by the proliferative tachyzoite stage. Despite a low degree of identity between the two amino acid sequences (24%), the conservative distribution of the cysteine and tryptophan residues, as well as of repeated motifs, together with oligopeptide identities suggest similar folding and possibly similar function for both proteins. PMID- 8206925 TI - Effect of selenium deficiency on type I 5'-deiodinase. AB - The type I iodothyronine 5'-deiodinase (5'-DI) present in rat liver and kidney has recently been demonstrated to be a selenoprotein. The goal of the present study was to examine in detail the effect of selenium (Se) deficiency on 5'-DI at the protein and mRNA levels. In weanling rats fed a selenium-deficient (Se(-)) diet for 6 weeks, 5'-DI activity was decreased 91 and 69% relative to control activities in liver and kidney, respectively. Administration of 3,5,3' triiodothyronine resulted in a 2-fold increase in 5'-DI activity in control animals, but had little or no effect on 5'-DI activity in Se(-) animals. Western analysis using a specific antiserum directed against a bacterial fusion protein containing the carboxyl-terminal half of the 5'-DI protein demonstrated that this decrease in 5'-DI activity in Se(-) animals was explained by a marked decrease in 5'-DI protein. Administration of Se to Se(-) animals resulted in parallel increases in 5'-DI protein and activity over a 72-h time period. It was also shown that selenium deficiency was accompanied by a 40% decrease in 5'-DI mRNA levels in the kidney, but not in the liver. In both tissues, the administration of 3,5,3'-triiodothyronine resulted in increased 5'-DI mRNA levels which were not altered by selenium status. These studies indicate that selenium deficiency decreases 5'-DI activity by decreasing the amount of 5'-DI protein. The mechanism of this impairment in enzyme synthesis appears to be a defect in translation, presumably due to a block in the UGA-directed selenocysteine incorporation in selenium deficiency. PMID- 8206926 TI - A new blood-coagulating protease in mitochondrial membranes of rat submaxillary glands. Purification and characterization of protease and its blood-coagulating activity. AB - An integral membrane protease was solubilized and purified to homogeneity from rat submaxillary mitochondria. The purified enzyme could coagulate rabbit plasma. The molecular mass of the enzyme is 22 kDa on SDS-polyacrylamide gel electrophoresis under reducing conditions and 24 kDa on gel filtration on a Sephadex G-100 column. Its isoelectric point is 4.2-4.25. Enzyme activity is strongly inhibited by diisopropyl fluorophosphate, soybean trypsin inhibitor, benzamidine, aprotinin, and antipain, suggesting the enzyme as a serine protease. Its pH optimum for activity is 8.5. Zn2+ is strongly inhibitory; at 1 mM concentration it produced 72% inhibition. The enzyme is active toward different synthetic substrates (p-nitroanilide derivatives) containing Arg at the P1 position with blocked NH2 terminus. Kcat/Km was highest with the substrate N-Bz Pro-Arg-pNa (where Bz is benzoyl and pNA is paranitroanilide). The purified enzyme coagulates rabbit plasma in a dose-dependent manner. Plasma coagulation by the enzyme is completely blocked in the presence of aprotinin or soybean trypsin inhibitor, suggesting that protease activity is required for this coagulation reaction. Antibody raised against the purified enzyme inhibits the plasma coagulation initiated by the enzyme. The enzyme can correct the prolonged clotting time of factor X-deficient human plasma but is unable to convert purified fibrinogen to fibrin clots, indicating factor Xa-like activity of the enzyme. The enzyme has the ability to activate prothrombin. Several properties of the enzyme distinguish it from other reported submaxillary proteases. PMID- 8206927 TI - Effects of guanosine 3',5'-bisdiphosphate (ppGpp) on rate of transcription elongation in isoleucine-starved Escherichia coli. AB - We measured the transcription elongation rate on two mRNA genes, i.e. infB and lacZ, and on a part of the rrnB gene under conditions when wild type (rel+) Escherichia coli and relaxed (relA) mutants were exposed to isoleucine starvation. The RNA chain growth rates were calculated from the time lag between induction of transcription and the appearance of specific hybridization to probes complementary to the 3' ends of the genes, i.e. from the transcription time. The rate of mRNA chain elongation responded differently in rel+ and relA strains exposed to isoleucine starvation as it decreased (approximately 50%) in rel+ strains that accumulated high concentrations of guanosine 3',5'-bisdiphosphate (ppGpp) and increased (approximately 15%) the relA mutant whose ppGpp pool decayed during starvation. These results show that ppGpp inhibits mRNA chain elongation in vivo. However, stable RNA chain elongation appeared unaffected by ppGpp pool size and was twice as fast as mRNA chain elongation in exponentially growing cells. PMID- 8206929 TI - Two pairs of oppositely charged amino acids from Jun and Fos confer heterodimerization to GCN4 leucine zipper. AB - The preferential assembly of Jun and Fos into heterodimers has been shown to be mainly driven by 16 amino acids (8 from each protein) situated in positions e and g of the leucine zipper coiled-coil structures of the two proteins (O'Shea, E. K., Rutkowski, R., and Kim, P. S. (1992) Cell 68, 699-708). Using a similar approach, we show that among these residues two pairs of oppositely charged amino acids account in fact for most of the additional free energy of heterodimerization in this system. These residues are 2 glutamic acid side chains in positions g1 and e2 of the Fos leucine zipper and 2 lysine residues in the equivalent positions of the Jun zipper. These amino acids were placed in the context of a GCN4 leucine zipper using peptide synthesis. These peptides contain unique cysteine residues enabling the formation of covalent dimers. The gain in heterodimer free energy has been determined both by cysteine-linked dimer formation under redox conditions and by thermal melting experiments of covalent dimers using circular dichroism experiments. The two pairs of oppositely charged residues (Glu,Glu and Lys,Lys) in positions g1 and e2 contribute at least -1.9 kcal/mol of additional free energy, accounting for a 50-fold excess of the heterodimer with respect to one of the homodimers. Thermal denaturation studies as a function of pH and ionic strength suggest that electrostatic effects should indeed be a major driving force for heterodimerization. On the contrary, peptides harboring the 12 amino acids from Jun and Fos in the other e and g positions (i.e. in e1, g2, e3, g3, e4, and g4) show only a moderate tendency to form heterodimers. PMID- 8206928 TI - Internalization of the constitutively active arginine 1152-->glutamine insulin receptor occurs independently of insulin at an accelerated rate. AB - Signals controlling the insulin receptor endocytotic pathway have been investigated using the R1152Q insulin receptor mutant (M). This mutant receptor exhibits high levels of insulin-independent kinase activity, impaired autophosphorylation, and lack of an insulin stimulatory effect on both auto- and substrate phosphorylation. NIH-3T3 fibroblasts expressing M receptors displayed a 2.5-fold higher 125I-insulin internalization rate than wild type (WT) but lacked insulin-induced receptor internalization and down-regulation. Cell surface recycling of internalized receptors also occurred at a higher rate in M cells and was unaffected by insulin. Cell preincubation with 35 mM Tris, which inhibits the insulin receptor degradative route, elicited no effect on M receptor recycling but inhibited that of WT by 40%. In contrast, the energy depleter 2,4 dinitrophenol, which inhibits normal insulin receptor retroendocytosis, impaired M receptor recycling 4-fold more effectively than that of WT. The release of internalized intact 125I-insulin was 6-fold greater in M than in WT fibroblasts and was almost completely inhibited by dinitrophenol, whereas insulin degradation by M cells was 4-fold decreased as compared with WT. Thus, internalization and recycling of the constitutively active Gln1152 receptor kinase occur in the absence of autophosphorylation. However, tyrosine phosphorylation appears to be required for proper sorting of endocytosed insulin receptors. PMID- 8206930 TI - The role of anions in pH regulation of Leishmania major promastigotes. AB - The pH regulation of Leishmania major promastigotes was studied as a function of the ionic composition of the medium and in response to acid and alkali load. Intracellular pH (pHi) was monitored by on-line ratio fluorescence using the fluorescence-dependent pH indicator 2',7'-bis-(carboxyethyl)-5,6 carboxyfluorescein (BCECF). In Cl(-)-based medium (pH 7.4, 30 degrees C), the steady state pHi was maintained at 6.75 +/- 0.01. Only a minor (< or = 0.07 +/- 0.02 unit) decrease in steady state pHi was observed when parasites were treated with H(+)-ATPase inhibitors such as vanadate, N-ethylmaleimide, or bafilomycin. After treatment with the impermeant anion transport blocker DIDS, or in the presence of the reduced analog H2DIDS, pHi decreased by > or = 0.2 unit. In gluconate-based medium, however, pHi gradually decreased to 6.53 +/- 0.05 and showed a swift but time-dependent recovery (alkalinization) when Cl- or other halides or nitrate were restored to the medium. That recovery was also inhibited by pretreating cells with DIDS or exposing them to H2DIDS. The findings provide evidence for Cl- transport mechanisms that support a pHi regulatory process which is operative in acidic-neutral cytoplasmic milieu. Under alkali load induced by weak base treatment, parasites undergo a rapid alkalinization which was followed first by a fast but limited acidification and subsequently by a slower but more robust acidification (recovery) to reach a pHi of 6.85 +/- 0.05. The recovery of pHi was markedly reduced in the presence of H2DIDS and/or in the absence of Cl- in the medium. Based on these results and on the fact that the natural parasite environment is both alkaline and rich in HCO3-/CO3(2-) ions, we propose (Cl-)o (HCO3-)i or (Cl-)o-(OH-)i exchange as the major mechanism of regulatory cell acidification which is operative upon cell alkalinization. The possibility that similar pH regulatory mechanisms are operative in Leishmania promastigotes in both acidic and alkaline conditions is considered. The putative pH regulatory mechanisms might serve as potential targets for therapeutic intervention. PMID- 8206931 TI - Purification and characterization of a novel deoxyinosine-specific enzyme, deoxyinosine 3' endonuclease, from Escherichia coli. AB - We have purified a novel endonuclease from Escherichia coli that recognizes deoxyinosine, a deamination product of deoxyadenosine in DNA. This activity, which we named deoxyinosine 3' endonuclease, is different from the known hypoxanthine DNA N-glycosylases which have been partially characterized in E. coli and other organisms. The enzyme was purified 24,800-fold to apparent homogeneity. SDS- and activity PAGE analyses indicate that the enzyme has an apparent molecular mass of 25 kDa. Deoxyinosine 3' endonuclease recognized deoxyinosine in both single- and double-stranded DNA but exhibited a 4-fold preference for double stranded over single-stranded DNA. In addition to deoxyinosine, the enzyme recognized urea residues and AP sites. Deoxyinosine 3' endonuclease has an obligatory requirement for Mg2+, but other cations such as Co2+ and Mn2+ could partially replace Mg2+. The optimal pH for deoxyinosine 3' endonuclease was around 7.5. In contrast to most of the known repair enzymes, deoxyinosine 3' endonuclease makes an incision at the second phosphodiester bond 3' to a deoxyinosine or AP site, leaving behind the intact lesion on the nicked DNA. Therefore, deoxyinosine 3' endonuclease recognizes, but does not remove, the lesion from the DNA molecule. The biological significance of this novel activity is discussed with reference to other repair activities in E. coli. PMID- 8206932 TI - Effect of 5-fluoro- and 5-bromouracil substitution on the translation of human thymidylate synthase mRNA. AB - The synthesis of thymidylate synthase (TS) from 5-fluorouracil (FUra)- and 5 bromouracil (BrUra)-substituted mRNAs was examined to investigate the effect of incorporation of uracil (Ura) analogs on translation. Human TS cDNA was transcribed in the presence of Ura-, FUra-, or BrUTP to obtain 100% substituted mRNA. The mRNAs were translated in a rabbit reticulocyte lysate system. The TS protein that was formed from each of the templates reacted identically with TS antibody in Western blots. Time courses of TS formation revealed a characteristic peak which occurred at 45 min for the Ura- and FUra-RNAs and at 2 h for the BrUra RNA. Substitution of Ura with FUra did not alter the rate of translation, while substitution of BrU for Ura decreased the rate of translation. Substitution of Ura with FUra or BrUra enhanced the stability of the mRNAs in the rabbit reticulocyte lysate by 3- and 10-fold, respectively. Incorporation of BrUra influenced the binding and catalysis on the ribosome, resulting in a 3.5-fold greater rate of activation (Kact) and 6-fold lower Vmax than the equivalent values for the Ura- and FUra-substituted mRNAs. Nondenaturing gel electrophoresis revealed that different conformations exist among the mRNAs. These data show that translation can be influenced by the incorporation of fraudulent bases into mRNA and those bases that stabilize RNA secondary structure will have the greatest inhibitory effect on translation. PMID- 8206933 TI - Expression and specificity of human GM2 activator protein. AB - The cDNA encoding GM2 activator was expressed in the Escherichia coli/pT7-7 system. The yield of the GM2 activator with greater than 99% purity was about 3 mg per liter culture. The recombinant GM2 activator was found to be as active as that isolated from human kidney. The availability of the recombinant GM2 activator enabled us to critically examine the specificity of this activator protein. Our results show that the specificity of GM2 activator is not as strict as that reported previously. Although GM2 activator stimulates most efficiently the degradation of GM2 carried out by beta-N-acetylhexosaminidase A (Hex A), this activator also stimulates the following reactions: (a) conversion of GM2 to GA2 by clostridial sialidase; (b) hydrolysis of GalNAc from dipalmitoylphosphatidylethanolamine-II3NeuAcGgOse3 by Hex A; and (c) liberation of Gal from GM1 by beta-galactosidase at a high activator concentration. Thus, this activator does not differentiate between GM2 and dipalmitoylphosphatidylethanolamine-II3NeuAcGgOse3 or between Hex A and clostridial sialidase. The micellar forms of GD2 and GalNAc-GD1a were found to be more readily hydrolyzed by Hex A than GM2 in the absence of GM2 activator. Our results also show that saposin B can enhance the stimulatory activity of GM2 activator, but it cannot promote the stimulatory activity of sodium taurodeoxycholate. Taken together, our results suggest that the mechanism of action of GM2 activator is different from saposin B, and the action of GM2 activator is more than to solubilize lipid substrates. The effectiveness of GM2 activator in stimulating the hydrolysis of GM2 may be due to its ability to recognize the specific trisaccharide structure of the GM2 epitope, GalNAc beta 1- >4(NeuAc alpha 2-->3)Gal-, and to modify the GalNAc-NeuAc interaction in this structure. PMID- 8206934 TI - Formation and stability of higher order chromatin structures. Contributions of the histone octamer. AB - Unique roles have been identified for the histone octamer in the formation and stabilization of higher order chromatin structures. Histone octamers were assembled onto 12 tandem repeats of Lytechinus 5 S rDNA, at either saturating or subsaturating ratios. The extent of oligonucleosome folding and intermolecular association in divalent salts was monitored using analytical and differential sedimentation techniques. Saturated oligonucleosomes (12 nucleosomes/DNA) sedimented at 29 S in very low salt buffer. In 1.0-2.0 mM MgCl2, saturated oligonucleosomes formed a maximally folded 55 S structure whose extent of compaction was equivalent to that of classical higher order 30-nm diameter chromatin structures. These results are in marked contrast to those obtained previously in NaCl, where the maximally folded oligonucleosome species sedimented at only approximately 40 S (Hansen, J. C., Ausio, J., Stanik, V. H., and van Holde, K. E. (1989) Biochemistry 28, 9129-9136). Mg(2+)-dependent formation of the 55 S conformation was inhibited by histone octamer depletion; the maximum sedimentation coefficient observed for rDNA molecules containing 10-11 nucleosomes in 2.0 mM MgCl2 was only 40 S. Above 2.0 mM MgCl2, the equilibrium was progressively shifted toward formation of large associated oligonucleosome species. The implications of these results to the mechanism of chromatin folding and its relationship to the biological activity of the chromatin fiber are discussed. PMID- 8206935 TI - Enhancement of rod outer segment GTPase accelerating protein activity by the inhibitory subunit of cGMP phosphodiesterase. AB - The cGMP phosphodiesterase (PDE) of retinal rod outer segments (ROS) is activated by the GTP-bound form of the G protein, transducin (Gt alpha). This activation can be reversed by the inhibitory gamma subunit of PDE through two distinct mechanisms: acceleration of GTP hydrolysis and direct inactivation independent of GTP hydrolysis. We have found that acceleration of Gt alpha GTPase by PDE gamma does not occur upon formation of a Gt alpha PDE gamma complex but rather reflects enhanced activity toward this complex of a membrane-bound GTPase accelerating protein. GTPase rate constants for Gt alpha in the presence of 3.3 microM PDE gamma were as high as 0.7 s-1 with hypotonically washed ROS membranes at 40 microM rhodopsin but were more than 10-fold lower when protein-free vesicles containing ROS lipids were substituted for ROS membranes. Acceleration of Gt alpha GTPase by PDE gamma was also barely detectable at low ROS concentrations (e.g. 4 microM rhodopsin) or if ROS treated with trypsin or urea were used. GTPase-independent inactivation by PDE gamma occurred efficiently at much lower membrane concentrations. Inhibition of Gt alpha-activated PDE was much slower than inhibition of PDE alpha beta by PDE gamma. Effects of PDE gamma upon successive additions of GTP suggested formation of a complex of PDE gamma and Gt alpha-GDP that is refractory to reactivation. PMID- 8206936 TI - Signal peptide cleavage regions. Functional limits on length and topological implications. AB - As a first step toward understanding the topology of the signal peptide with respect to the membrane during the protein export process, we have examined the constraints on the length of the cleavage region needed to achieve signal peptidase recognition and cleavage. Using the signal peptide of Escherichia coli alkaline phosphatase, a series of cleavage region mutants has been constructed. Variations in length were brought about by replacing the wild type cleavage region of the signal peptide with polymers of increasingly more residues. In each case, alanine residues are used exclusively in the -1 and -3 positions to provide only one viable cleavage site. Glutamine residues are used in all other positions in order to vary the length from 3 to 13 total residues. Analysis of these mutants revealed that cleavage regions ranging from 3 to 9 residues are completely and efficiently processed. The extent of processing drops substantially thereafter, with no processing observed for signal peptides with 13 residue long cleavage regions. A second mutant with a 13-residue long cleavage region was designed and analyzed to ensure that the lack of processing reflected a cleavage problem and not a translocation defect. The results are consistent with the notion that the signal peptidase active site is in close proximity to the periplasmic surface of the inner membrane and that interaction of the cleavage region with the signal peptidase probably depends on, and is constrained by, other interactions involving the signal peptide. PMID- 8206937 TI - The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo. AB - We have used polyclonal antibodies against an internal peptide (residues 169 to 182; Ab169/182) and a peptide corresponding to the carboxyl terminus (residues 299 to 309; Ab299/309) to look for in vivo modifications of protein phosphatase 2A catalytic (PP2Ac) subunit. Treatment of extracts from human breast cancer (MCF7) cells with either alkali or ethanol increased immunoreactivity of PP2Ac subunit severalfold on Western blots with Ab299/309, but did not apparently change molecular weight or isoelectric point of the protein. In contrast, immunoreactivity with Ab169/182 was unchanged by these treatments. Subsequently, we demonstrated that the increase in PP2Ac subunit recognition by Ab299/309 coincides with the demethylation of this protein at the carboxyl-terminal leucine (Leu309). Methylation of PP2Ac subunit, in vitro, increases its activity toward both phosphorylase a and a phosphopeptide. The carboxyl-terminal sequence (TPDYFL) of PP2Ac subunit is completely conserved between mammals, yeast, fruit fly, and plants which suggests that regulation of this enzyme activity by carboxyl-terminal methylation has been conserved during evolution. PMID- 8206938 TI - Surface-induced alterations in the kinetic pathway for cleavage of human high molecular weight kininogen by plasma kallikrein. AB - We have studied the cleavage of human high molecular weight kininogen (HK) by plasma kallikrein in the absence and presence of the surfaces, dextran sulfate (DxSO4) and sulfatides. Using a combination of SDS-polyacrylamide gel electrophoresis, Western blotting with polyclonal antibodies that specifically recognize the COOH terminus of the bradykinin moiety, and high pressure liquid chromatography analyses of the cleavage reaction, we have identified two intermediates in the formation of bradykinin from intact kininogen and demonstrated that alternative cleavage pathways are followed in the absence and presence of surfaces. The COOH-terminal bradykinin cleavage occurred first both in the absence and presence of DxSO4, producing a 103-kDa HK intermediate consisting of disulfide-linked heavy and light chains that retained the kinin moiety. In the presence of DxSO4, this was followed exclusively by the NH2 terminal bradykinin cleavage and release of kinin with no apparent change in molecular mass. Subsequently, a slower cleavage of an 8-kDa peptide from the amino terminus of the HK light chain occurred to form a 95-kDa end product. In contrast to this sequential cleavage pattern, NH2-terminal bradykinin and light chain cleavages occurred randomly in the absence of DxSO4, resulting in the production of an additional 95-kDa intermediate that retained bradykinin but had lost the 8-kDa peptide from the HK light chain. Comparison of the relative rates of the three kallikrein cleavages in the absence and presence of DxSO4 indicated that the surface enhanced the rates of both bradykinin cleavages 2-4-fold, but inhibited the light chain cleavage rate approximately 10-fold, thereby accounting for the change from a partially random to a sequential cleavage pattern in the presence of the surface. Steady-state kinetic analysis revealed that DxSO4 enhanced the kcat/KM for bradykinin release by the rate-limiting NH2-terminal bradykinin cleavage by approximately 2-fold due exclusively to an increase in kcat. Sulfatides appeared to produce the same effects on the pattern of HK cleavages as DxSO4. Blocking of the nonactive site, i.e. exosite, interaction between kallikrein and HK with excess prekallikrein or a synthetic peptide containing the region of HK that interacts with the kallikrein exosite significantly reduced the rate of bradykinin release as well as HK cleavages detected by SDS-polyacrylamide gel electrophoresis either in the absence or presence of DxSO4, indicating that the exosite interaction facilitates bradykinin cleavage. PMID- 8206939 TI - Role of p67-phox SH3 domains in assembly of the NADPH oxidase system. AB - Src homology 3 (SH3) domains direct cellular localization and signal transduction through specific protein-protein interactions with proline-rich target sequences. The two SH3 domain in p67-phox, a cytosolic component of the phagocyte NADPH oxidase system, may mediate interactions within the oxidase complex and direct its translocation to membranes. The requirement for SH3 domains in p67-phox was studied both in cell-free and whole cell oxidase assay systems. The amino terminal domain of p67-phox (amino acids 1-246) that lacks both SH3 domains was active in vitro. Various forms of p67-phox lacking one or both SH3 domains were produced in whole cells using episomal expression vectors to stably transfect p67 phox-deficient Epstein-Barr virus-B cells derived from chronic granulomatous disease patients. Complete restoration of NADPH oxidase activity was achieved with full-length p67-phox cDNA expression. Deletion of either SH3 domain resulted in dramatic reductions of NADPH oxidase activity relative to corrected transfected cells, which correlated with decreases in membrane binding. Deletion of both SH3 domains completely abolished p67-phox membrane binding and oxidase activity. Thus, in contrast to oxidase reconstitution in a cell-free system, we observed a requirement for both SH3 motifs for restoration of oxidase activity and binding of p67-phox to membranes. PMID- 8206940 TI - rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel Ras related protein. AB - Neuronal activity results in long term cellular changes that underlie normal brain development and synaptic plasticity. To examine the molecular basis of activity-dependent plasticity, we have used differential cloning techniques to identify genes that are rapidly induced in brain neurons by synaptic activity. Here we describe an inducible novel member of the Ras family of small GTP-binding proteins we have termed Rheb. rheb mRNA is rapidly and transiently induced in hippocampal granule cells by seizures and by NMDA-dependent synaptic activity in the long term potentiation paradigm. The predicted amino acid sequence of Rheb is most closely homologous to yeast Ras1 and human Rap2. The putative GTP binding regions are highly conserved. A bacterial fusion protein of Rheb binds GTP and exhibits intrinsic GTPase activity. Like Ha-Ras, the carboxylterminal sequence encodes a CAAX box that is predicted to signal post-translational farnesylation and to target Rheb to specific membranes. rheb mRNA is expressed at comparatively high levels in normal adult cortex as well as a number of peripheral tissues, including lung and intestine. In the developing brain, rheb mRNA is expressed at relatively high levels in embryonic day 19 cortical plate, and expression remains at stable levels throughout the remainder of prenatal and postnatal development. Its close homology with ras and its rapid inducibility by receptor-dependent synaptic activity suggest that rheb may play an important role in long term activity-dependent neuronal responses. PMID- 8206941 TI - Putative Drosophila pheromone-binding proteins expressed in a subregion of the olfactory system. AB - Four genes expressed in the olfactory system of Drosophila melanogaster have been identified by subtractive hybridization. Two of these genes, OS-E and OS-F, are related to genes encoding moth pheromone-binding proteins. The OS-E and OS-F genes are tightly linked and are expressed in a subregion of the antenna (the primary olfactory organ). A protein sequence analysis suggests the possibility that pheromone-binding proteins are members of a larger class of proteins, extending beyond the olfactory system. The predicted product of a third gene, OS D, shares features common to vertebrate odorant-binding proteins, but has a primary structure unlike odorant-binding proteins. The fourth gene, OS-C, encodes a novel 13-kDa protein that contains a putative nuclear import sequence and an acid-rich region. The expression patterns of these genes differ within the antenna; their transcript distributions support the notion of specialized roles for different olfactory sensilla. The functions of the OS gene products have not been demonstrated; however, the potential identification of pheromone-binding proteins in Drosophila, a species with well characterized genetics, may offer a means of analyzing the function of these molecules that is not available in other systems. PMID- 8206942 TI - Biochemical studies of three Saccharomyces cerevisiae acyl-CoA synthetases, Faa1p, Faa2p, and Faa3p. AB - The efficiency and specificity of protein N-myristoylation appear to be influenced by the availability of myristoyl-CoA and other potential acyl-CoA substrates of myristoyl-CoA:protein N-myristoyltransferase. Recent studies have revealed that Saccharomyces cerevisiae contains at least three acyl-CoA synthetase genes (FAA for fatty acid activation). We have expressed Faa1p, Faa2p, and Faa3p in a strain of Escherichia coli that lacks its own endogenous acyl-CoA synthetase (FadD). Each S. cerevisiae acyl-CoA synthetase contained a carboxyl terminal His tag so that it could be purified to homogeneity in a single step using nickel chelate affinity chromatography. In vitro assays of C3:0-C24:0 fatty acids indicate that Faa1p prefers C12:0-C16:0, with myristic and pentadecanoic acid (C15:0) having the highest activities. Faa2p can accommodate a wider range of acyl chain lengths: C9:0-C13:0 are preferred and have equivalent activities, although C7:0-C17:0 fatty acids are tolerated as substrates with no greater than a 2-fold variation in specific activity. The myristoyl-CoA synthetase activities of Faa1p and Faa2p are 2 orders of magnitude greater than that of Faa3p in vitro. Faa3p has a preference for C16 and C18 fatty acids with a cis-double bond at C-9 C-10. The temperature optimum for Faa1p is 30 degrees C, while Faa2p and Faa3p have the greatest activities at 25 degrees C. These in vitro observations were confirmed using two in vivo assays: (i) measurement of the ability of each S. cerevisiae acyl-CoA synthetase to direct the incorporation of exogenously derived tritiated myristate, palmitate, or oleate into cellular phospholipids produced in a fadD- strain of E. coli during exponential growth at 24 or 37 degrees C and (ii) measurement of the incorporation of [3H]myristate into a yeast N myristoylprotein coexpressed with Nmt1p and Faa1p, Faa2p, or Faa3p in the fadD- strain. PMID- 8206943 TI - Identification of a 3'-->5'-exonuclease that removes cytosine arabinoside monophosphate from 3' termini of DNA. AB - Cytosine arabinoside monophosphate (araCMP) at the 3' terminus of DNA constitutes a lesion that impedes further synthesis by DNA polymerase alpha (DNA pol alpha). A biochemical assay has been designed to detect 3'-->5'-exonucleases in cell extracts that remove the 3'-araCMP lesion in an oligonucleotide template-primer and permit subsequent extension by DNA pol alpha. The major 3'-->5'-exonuclease activity in human myeloblast extracts has been purified, and gel filtration chromatography of the purified enzyme indicates that the exonuclease has an apparent native molecular mass of 52 kDa. Incubation of the enzyme with a 5'-32P labeled araCMP template-primer results in exonucleolytic degradation of the primer exclusively in the 3'-->5' direction, demonstrating that the enzyme is a 3'-->5'-exonuclease. The products of the 3'-->5'-exonuclease reaction are 5' mononucleotides. The apparent rate of araCMP removal by the exonuclease is approximately the same as the rate of deoxynucleoside monophosphate (dNMP) removal. Furthermore, the apparent rates of 3'-terminal excision are approximately the same whether the oligomer is hybridized to a complementary oligonucleotide, or not, indicating that the enzyme has both single- and double stranded 3'-->5'-exonuclease activity. The enzyme does not possess 5'-->3' exonuclease activity, nor is it associated with DNA polymerase activity. In addition, the enzyme does not cleave 3'-phosphoryl-terminated DNA, and it does not cleave RNA. The enzymatic characteristics of the isolated 3'-->5'-exonuclease indicate that it is distinct from previously identified mammalian deoxyribonucleases. PMID- 8206944 TI - Plasmodium falciparum S-adenosylhomocysteine hydrolase. cDNA identification, predicted protein sequence, and expression in Escherichia coli. AB - Compounds that specifically inhibit S-adenosylhomocysteine hydrolase (SAHH; EC 3.3.1.1) interfere with the proliferation of Plasmodium malarial parasites, but efforts to identify the enzyme directly in parasite extracts have been unsuccessful. Here we report genetic and biochemical evidence for the presence of a gene encoding P. falciparum SAHH. The gene is transcribed as a 2.8-kilobase mRNA in erythrocytic stage parasites. Analysis of the open reading frame predicts a 53.9-kDa protein having conserved regions thought to be involved in NAD binding. The cDNA sequence has been incorporated into an Escherichia coli expression construct to confirm the function of the sahh product. Transformed E. coli cells produce a protein with a relative molecular weight of 56,000 which possesses SAHH activity as evidenced by the conversion of 3-deazaadenosine to S-3 deazaadenosylhomocysteine. Several amino acid residues that have been suggested to be at the SAHH active site in other organisms show nonconserved replacements in P. falciparum, suggesting that some current proposals for the enzyme mechanism may need to be revised. The structural differences between the P. falciparum and mammalian SAHH enzymes may foster innovative strategies for drug development against malaria. PMID- 8206945 TI - Topoisomerase IV can support oriC DNA replication in vitro. AB - Escherichia coli has two type II topoisomerases, DNA gyrase and topoisomerase IV (Topo IV). Topo IV is required for the decatenation of the linked daughter chromosomes at the terminal stages of DNA replication, whereas gyrase, because of its ability to convert to negative supercoils the positive supercoils generated by replication fork progression in a circular chromosome, is required to support nascent chain elongation. Using an oriC DNA replication system in vitro, we show that Topo IV, which can relax positive supercoils, can also support replication fork progression. This activity is only observed at substoichiometric ratios of Topo IV to template, at higher ratios, the template becomes relaxed and initiation of DNA replication cannot occur. Topo IV was capable of supporting bidirectional DNA replication from oriC, although, unlike the case with gyrase, some templates apparently replicated unidirectionally. This suggests that either gyrase itself or a certain minimum superhelical density is required for proper initiation of DNA replication from oriC. PMID- 8206946 TI - Human hepatic triglyceride lipase expression reduces high density lipoprotein and aortic cholesterol in cholesterol-fed transgenic mice. AB - We have produced a line of transgenic mice expressing human hepatic triglyceride lipase (hH-TGL) to examine the in vivo effects of hepatic lipase expression on high density lipoprotein catabolism. Activation of metallothionine I promoter-hH TGL cDNA transgene produced high levels of lipase mRNA in liver, heart, and kidney and elevated enzyme activity as assayed in post-heparin plasma. In a series of hyperlipidemic diet studies in which zinc was included in the diet to induce the transgene, hH-TGL expression was associated with a 34% lowering of plasma HDL-cholesterol levels (p < 0.01) when compared with animals on the same hyperlipidemic diet without zinc. This lowering of HDL cholesterol was paralleled by a decrease in total cholesterol and a decrease in HDL particle size. SDS polyacrylamide gel electrophoresis analysis of the smaller HDL particles revealed that apolipoprotein AI was still the major apoprotein associated with the HDL. Quantitative analysis of abdominal aortic cholesterol content from the same animals suggests that the observed changes in plasma HDL by hH-TGL over expression correlated with a decrease in the accumulation of aortic cholesterol (42%, p < 0.01). These data support the hypothesis that hH-TGL mediates a non receptor pathway for the clearance of cholesterol from the plasma compartment. PMID- 8206948 TI - Involvement of Jun and Fos proteins in regulating transcriptional activation of the human pi class glutathione S-transferase gene in multidrug-resistant MCF7 breast cancer cells. AB - Elevated levels of the human pi class glutathione S-transferase (GSTP1-1) have been implicated in the development of antineoplastic drug resistance. Using GSTP1 promoter deletion constructs we have shown that enhanced GSTP1 transcription (up to 18-fold) is the predominant mechanism responsible for increased GSTP1-1 levels in a multidrug resistant derivative (VCREMS) of the human mammary carcinoma cell line MCF7. Furthermore, disruption of a putative AP-1 response element within the GSTP1 promoter (nucleotides -69 to -63) abrogated GSTP1 transcription in both cell lines. In addition, band shift assays demonstrated binding of a VCREMS nuclear complex to the promoter region C1 (-73 to -54) which could be competed for by a DNA fragment containing a known AP-1 binding site from the human collagenase promoter. However, no such competition was observed for the major MCF7 C1 complex. The role of a Fos-Jun-like complex in regulating GSTP1 transcription in VCREMS cells was further emphasized by the introduction of point mutations within the C1 region which were known to inhibit AP-1 binding and the interaction of antisera raised against human c-Jun and c-Fos with the major C1 complex in VCREMS cells. These studies therefore highlight cell-specific differences in the binding pattern of Jun and Fos proteins to the GSTP1 promoter which are likely to play an important role in regulating transcriptional activation of the GSTP1 gene in drug-resistant breast cancer cells. PMID- 8206947 TI - Myristylation-dependent transactivation by FBR v-fos is regulated by C/EBP. AB - Viral oncogenes are generally believed to cause transformation through disregulated mimicry of their cellular homologues. However, here we show that FBR v-fos, unlike c-fos, transcriptionally activates unique genes in retrovirally induced chondro-osseous sarcomas. We show that FBR v-fos transactivates the collagen III and stromelysin promoters and that the unique transcriptional properties of transforming FBR depend upon its N-terminal myristylation and the differentiation state of the cell. Deletion or mutation of the myristylation site results in a loss of FBR v-fos transactivation in HeLa and undifferentiated 3T3 L1 preadipocyte cell lines. FBR v-fos transactivation of collagen III maps to a negative regulatory site which binds a key regulator of adipocyte differentiation, C/EBP alpha. Cotransfection of C/EBP alpha abolishes FBR v-fos transactivation of the alpha 1(III) collagen promoter. Furthermore, FBR v-fos cannot transactivate collagen III subsequent to adipocyte differentiation. We also demonstrate that collagen III transcription is reduced during adipocyte differentiation as the transcriptional activity of C/EBP alpha is concomitantly induced. Our results indicate that FBR v-fos transactivation depends upon its cotranslational myristylation and maps to a negative regulatory region which binds C/EBP alpha. PMID- 8206949 TI - Partial purification and characterization of the N-acetylglucosaminyl phosphatidylinositol de-N-acetylase of glycosylphosphatidylinositol anchor biosynthesis in African trypanosomes. AB - N-Acetylglucosaminylphosphatidylinositol (GlcNAc-PI) de-N-acetylase was solubilized from the bloodstream form of African trypanosomes using Zwittergent 3 14. The solubilized GlcNAc-PI de-N-acetylase was assayed using radiolabeled GlcNAc-PI substrates. The enzyme was partially purified about 140-fold from washed trypanosome membranes using conventional liquid chromatography. The enzyme has a Km of 1.5 microM. Replacement of the di-O-substituted D-myo-inositol of the natural GlcNAc-PI substrate by the L-myo-inositol isomer did not significantly alter the ability of the compound to act as a substrate for the de-N-acetylase, suggesting that the C-2 to C-5 hydroxyl groups of the myoinositol ring do not play a critical role in substrate recognition. A substrate analogue lacking fatty acids was a relatively poor substrate for the enzyme, indicating that the lipid component plays an important role in substrate recognition and/or presentation of the substrate to the enzyme in detergent micelles. Substrate analogues lacking the glycerophosphate component were not recognized by the enzyme, suggesting that this component is important in the substrate recognition process. PMID- 8206950 TI - Unique structural features important for stabilization versus polarization of the alpha 2A-adrenergic receptor on the basolateral membrane of Madin-Darby canine kidney cells. AB - The alpha 2A-adrenergic receptor (alpha 2AAR) is polarized to the basolateral membrane of Madin-Darby canine kidney cells via direct targeting. Examination of mutant alpha 2AAR reveals that direct delivery is independent of NH2-terminal glycosylation, COOH-terminal acylation, or protein sequences within the large third cytoplasmic loop or COOH-terminal tail. Combined mutation of these structural features also does not perturb alpha 2AAR delivery, suggesting that a three-dimensional structure imparted by non-contiguous endofacial sequences does not confer alpha 2AAR targeting and that motifs in or near the bilayer must be involved in targeting of the alpha 2AAR. Mutation of a conserved Asp residue in transmembrane two that alters receptor-G-protein interactions also does not impair alpha 2AAR targeting. Finally, modification of sequences in transmembrane seven that resemble tyrosine-containing endocytosis motifs utilized for targeting by some proteins does not perturb alpha 2AAR sorting. Interestingly, deletion of the large third cytoplasmic loop of the alpha 2AAR decreases receptor half-life on the basolateral surface from approximately 11 to 4.5 h without altering the ability of the alpha 2AAR to couple to G-proteins. These data suggest that although targeting of the alpha 2AAR likely involves bilayer sequences, the third cytoplasmic loop may contain structural features that promote stabilization of the alpha 2AAR on the basolateral surface of Madin-Darby canine kidney cells. PMID- 8206951 TI - Estrogen regulation of the insulin-like growth factor I gene transcription involves an AP-1 enhancer. AB - As a step toward elucidating the physiological role of insulin-like growth factor I (IGF-I) in mediating estrogen action, we sought to determine the molecular basis of the phenomenon. In HepG2 cells expressing exogenous estrogen receptors (ER), a reporter gene plasmid containing 600 base pairs of the chicken IGF-I promoter enhanced expression of luciferase 8.6-fold in response to 10(-6) M 17 beta-estradiol, indicating that the IGF-I promoter is a target of estrogen regulation. Although no conventional estrogen-responsive element was identified within the promoter fragment, the AP-1 motif located therein was shown to be essential; the estrogen-responsive enhancement of the Fos-Jun binding to the AP-1 motif, which takes place by means of post-translational modification, mediates the estrogen action. A direct or indirect interaction between the estrogen-ER complex and the Fos-Jun complex seems to facilitate the Fos-Jun binding to the target DNA. Although ER binding to the target DNA was not considered to be involved in the signaling pathway, the DNA binding domain-deficient ER did not mediate the phenomenon, providing support for the existence of a unique function of the DNA binding domain of ER in facilitating some protein-protein interaction. In conclusion, our present observations demonstrate that the chicken IGF-I gene promoter is controlled by estrogen through a unique pathway involving Fos, Jun, and the DNA binding domain of ER. PMID- 8206952 TI - An alternative transcript of the chick type III collagen gene that does not encode type III collagen. AB - Type III collagen, a ubiquitous protein found in most connective tissues, is not present in hyaline cartilage. However, we have identified an alternative transcript of the type III collagen gene in cultured chondrocytes from several embryonic chick cartilages. This RNA contains exons 24-52, but exons 1-23 are replaced by 70 nucleotides of unique sequence, suggesting that transcription initiates at an alternative promoter. Two of the open reading frames in the alternative transcript are out of frame with the collagen coding sequence; a third open reading frame encodes the carboxyl-terminal two-thirds of the collagen sequence. Thus, this RNA cannot serve as a template for synthesis of normal type III collagen and may encode noncollagenous proteins and/or a truncated collagen. The alternative transcript has been detected as early as 2.5 days of embryogenesis and at later stages is present at low levels in many tissues, including limb mesenchyme and cartilage. These results, together with our previous identification of an alternative transcript of the chick alpha 2(I) collagen gene (Bennett, V. D., and Adams, S. L. (1990) J. Biol. Chem. 265, 2223 2230), suggest that some collagen genes may have alternative functions that are independent of their roles in collagen production. PMID- 8206953 TI - Identification of volatile forms of methyl groups released by Halobacterium salinarium. AB - halobacterium salinarium (formerly H. halobium) is a chemotactic and phototactic archaeon from which volatile methyl groups are released continually, a phenomenon related to its sensory system. We found that released methyl groups comprised two different chemical species, methanol and methanethiol, the sulfur analog of methanol. Radiolabeling experiments showed that the methyl groups of both compounds, as well as the sulfur of methanethiol, were derived from methionine but were donated to cellular components and subsequently cleaved to produce the respective volatile compounds. Previous work had shown that chemostimuli and photostimuli result in transient increases in the rate of release of volatile methyl groups. We found that these increases reflected increased release of methanol but not of methanethiol. Thus, the methyl group chemistry of the H. salinarium sensory system is analogous to the well-studied chemotactic system of Escherichia coli. The reactions that result in methanethiol release are of unknown function and have unusual features. They may involve a methionine-gamma lyase activity we detected in H. salinarium. Sulfur derived from methionine was found attached to specific proteins in reduction-sensitive disulfide linkages. PMID- 8206954 TI - Contacts of the ABF1 protein of Saccharomyces cerevisiae with a DNA binding site at MATa. AB - The ABF1 protein of Saccharomyces cerevisiae is a multifunctional DNA-binding protein that is required for cell viability. The ABF1 protein has previously been shown to bind to a number of yeast sequences having a consensus of: 5'-A/G TC A/G C/T C/T NNNNACG-3'. A heretofore undiscovered ABF1-binding site was found in the MATa region. We have used missing contact analysis of this ABF1-binding site to show that removal of the conserved bases, as well as of some bases which are not conserved, reduces binding. We have probed contacts of ABF1 with the DNA-binding site using dimethyl sulfate and potassium permanganate and find that the protein makes extensive contacts with both the major and minor grooves. Ethylation interference studies indicate that numerous phosphate contacts are also important for ABF1 binding. Interference studies indicate that the ABF1 protein is also in close proximity to the DNA that is 5' and 3' of the conserved bases of the binding site. The extensive DNA contacts exhibited by ABF1 may play a role in the protein-induced bending of the DNA target (McBroom, L. D. B., and Sadowski, P. D. (1994) J. Biol. Chem. 169, 16461-16468). PMID- 8206955 TI - DNA bending by Saccharomyces cerevisiae ABF1 and its proteolytic fragments. AB - The ABF1 protein of the yeast Saccharomyces cerevisiae has been found to bend the DNA containing the target site for DNA binding. A bend angle of about 120 degrees was measured and the bend center was 7 base pairs to the 5' end of the ABF1 consensus-containing sequence. Phasing analysis showed that intact ABF1 bends the DNA towards the minor groove. We have subjected ABF1 to partial proteolysis and have found that proteolytic fragments were able to bind to the DNA-binding site and induce partial bends in the DNA. Interestingly, the locations of the bend centers, the bend angles, and the plane of the bends induced by the proteolytic peptides of ABF1 were different from those of the intact protein. We present a model for the mechanism of bending of DNA by ABF1. PMID- 8206956 TI - Participation of the bacteriophage Mu A protein and host factors in the initiation of Mu DNA synthesis in vitro. AB - During bacteriophage Mu transposition, strand transfer is catalyzed in the presence of phage-encoded A and B proteins and Escherichia coli HU protein, attaching Mu ends to target DNA and creating an intermediate in transposition. Bacteriophage Mu A protein, which remains tightly bound to the Mu ends in the native strand-transfer intermediate, blocked initiation of Mu DNA replication by a system of 8 host proteins (DnaB helicase, DnaC protein, DnaG primase, DNA polymerase III holoenzyme, DNA polymerase I, DNA gyrase, DNA ligase, and single strand binding protein). This 8-protein system had all enzymatic activities to convert the deproteinized intermediate to a cointegrate; however, additional host factor(s) were required to replicate the native intermediate. While replication of the native intermediate absolutely required DnaB helicase, DnaC protein, and DNA polymerase III holoenzyme, the specific requirements were relaxed for the deproteinized intermediate. Other host factors were able to replace these specific factors. These results indicate that Mu A protein, in conjunction with additional host factor(s), acts to promote assembly of specific host replication proteins at the Mu replication fork. This process may alter the stable interaction of Mu A protein with the ends to allow initiation of Mu DNA synthesis. PMID- 8206957 TI - Preproteins of chloroplast envelope inner membrane contain targeting information for receptor-dependent import into fungal mitochondria. AB - The amino-terminal transit sequences of two preproteins destined for the chloroplast inner envelope membrane show similarities to mitochondrial presequences in the prevalence of positive charges and the potential formation of an amphipathic alpha-helix. We studied if these preproteins could be imported into mitochondria and found a low, yet significant import into isolated plant mitochondria. The plant mitochondria were previously shown not to import precursors of chloroplast stromal or thylakoidal proteins. To analyze the specificity of import into mitochondria we used the established import systems of fungal mitochondria. The envelope preproteins were efficiently imported into Saccharomyces cerevisiae or Neurospora crassa mitochondria. Their import showed the characteristics of specific mitochondrial protein uptake, including a requirement for the main receptor MOM19 (mitochondrial outer membrane protein of 19 kDa) and a membrane potential across the inner membrane, and depended on the presence of the chloroplast transit sequence. We conclude that some chloroplast transit sequences contain sufficient information for specific interaction with mitochondrial import receptors (at least from fungal sources). PMID- 8206958 TI - Aliphatic alcohols stabilize an alternative conformation of the tryptophan synthase alpha 2 beta 2 complex from Salmonella typhimurium. AB - The conformational changes that accompany association of the tryptophan synthase alpha and beta 2 subunits are probed by investigating the effects of solvents on the catalytic and spectroscopic properties of tryptophan synthase. Low concentrations of ethanol, propanol, and butanol inhibit conversion of L-serine and indole to L-tryptophan by the alpha 2 beta 2 complex. Inhibition depends on the concentration, chain length, and hydrophobicity of the alcohol. In contrast, these alcohols increase the rates of conversion of beta-chloro-L-alanine and indole to L-tryptophan and of L-serine to pyruvate. Thus, alcohols alter the substrate specificity and reaction specificity of the alpha 2 beta 2 complex. These altered specificities are similar to those of the free beta 2 subunit in aqueous solution. The spectroscopic properties of enzyme-substrate intermediates formed by the alpha 2 beta 2 complex in 3 M ethanol and 0.5 M 1-butanol also resemble the intermediates formed by the free beta 2 subunit in aqueous solution. Experiments using gel-filtration, membrane ultrafiltration, and limited proteolysis show that the alpha 2 beta 2 complex does not dissociate at low concentrations of alcohols. Our results provide evidence that alcohols can stabilize an alternative conformation of the alpha 2 beta 2 complex which is similar to the open conformation of the free beta 2 subunit in aqueous solution. PMID- 8206959 TI - Drosophila kinesin minimal motor domain expressed in Escherichia coli. Purification and kinetic characterization. AB - A truncated motor domain of the alpha subunit of Drosophila kinesin was obtained by expression in Escherichia coli and purified to homogeneity in the presence of MgATP. This domain (designated DKH340) extends from the N terminus to amino acid 340. The isolated protein contains a stoichiometric level of tightly bound ADP and has a low basal rate of ATP hydrolysis of 0.029 +/- 0.002 s-1 in the absence of microtubules. The rate of release of bound ADP is 0.026 +/- 0.003 s-1. The approximate equality of the ADP release rate and the steady state ATPase rate indicates that ADP release is the rate-limiting step in ATP hydrolysis in the absence of microtubules. The rate of ATP hydrolysis is stimulated 3000 fold-by addition of microtubules (MT) (kcat = 80 s-1; KMT0.5,ATPase = 160 nM for half saturation of the ATPase rate by microtubules at saturating ATP levels; KMT0.5ATPase = 43 microns for half-saturation of the ATPase rate by ATP at saturating microtubule levels). Binding of DKH340 to MTs is biphasic in the presence of adenosine 5-(beta-gamma-imido)t-riphosphate. One DKH340 binds tightly per tubulin heterodimer, but greater than one DKH340/tubulin heterodimer can be bound at higher ratios of DKH340/microtubules. In the presence of MgATP, KMT0.5,Binding for physical binding of DKH340 to microtubules is weaker than KMT0.5,ATPase for stimulation of hydrolysis. These results are consistent with a model in which DKH340 cycles on and off the microtubule during hydrolysis of each ATP molecule. For this model, the kcat/KMT0.5,ATPase ratio of 5 x 10(8) M-1 s-1 is at least as large as the bimolecular rate constant for association with microtubules, and this value approaches the diffusion controlled limit. Nucleotide-free DKH340 can be produced by gel filtration in the absence of Mg2+, but it reforms tightly bound ADP slowly in the presence of MgATP (t1/2 > or = 10 min), and thus it is likely to be in a conformational state which is not produced during steady state ATP hydrolysis. PMID- 8206960 TI - Drosophila kinesin motor domain extending to amino acid position 392 is dimeric when expressed in Escherichia coli. AB - A truncated domain of the alpha-subunit of Drosophila kinesin was obtained by expression in Escherichia coli and purified to homogeneity in the presence of MgATP. This domain (designated DKH392) extends to amino acid 392 and contains the complete N-terminal region of kinesin which is highly conserved between species. The DKH392 construct includes an additional 52 amino acids beyond the minimal motor domain of 340 amino acid residues which has been previously characterized as DKH340 (Huang, T.-G., and Hackney, D. D. (1994) J. Biol. Chem. 269, 16493 16501). The s20,w values for DKH340 and DKH392 are 3.3 and 5.2 S and the D20,w values are 7.7 x 10(-7) and 4.9 x 10(-7) cm3 s-1, respectively. These results indicate that DKH340 is a monomer in solution, but DKH392 is a dimer. In the presence of adenosine 5-(beta,gamma-imido)triphosphate, DKH392 binds to microtubules with a stoichiometry of two head domains (one DKH392 dimer) per tubulin heterodimer in contrast to the tight binding of one DKH340 per tubulin heterodimer. Electron microscopy indicates that both DKH340 monomers and DKH392 dimers decorate microtubules with a periodicity of 8 nm. PMID- 8206961 TI - The rate-limiting step in microtubule-stimulated ATP hydrolysis by dimeric kinesin head domains occurs while bound to the microtubule. AB - DKH392 is a construct which contains the first 392 amino acids of the alpha subunit of Drosophila kinesin and is dimeric in solution (Huang, T.-G., Suhan, J., and Hackney, D. D. (1994) J. Biol. Chem. 269, 16502-16507). The ATPase rate of DKH392 was 0.005 s-1 in the absence of MTs. One ADP bound tightly to each subunit and the release of this ADP was the rate-limiting step in ATP hydrolysis. Microtubules accelerated the rate of ADP release and increased the rate of steady state ATP hydrolysis by almost 10,000-fold (kcat = approximately 45 s-1). The KMT0.5,ATPase value for saturation of the stimulation of the ATPase reaction by microtubules was 50 nM at 8 nM DKH392, but decreased at lower concentrations of DKH392. Physical binding of DKH392 to microtubules in the presence of 1 mM MgATP paralleled saturation of the stimulation of the ATPase activity by microtubules indicating that the rate-limiting step in microtubule-stimulated ATP hydrolysis occurs while DKH392 is bound to the microtubule. These results suggest that microtubule-stimulated ATP hydrolysis by DKH392 may be processive with the hydrolysis of multiple ATP molecules during each diffusional encounter of DKH392 with a microtubule. PMID- 8206962 TI - Sphingosine 1-phosphate, a novel signaling molecule, stimulates DNA binding activity of AP-1 in quiescent Swiss 3T3 fibroblasts. AB - Sphingosine and sphingosine 1-phosphate, metabolites of sphingolipids, stimulate cell proliferation in quiescent Swiss 3T3 fibroblasts and induce transient increases in intracellular free calcium (Zhang, H., Desai, N. N., Olivera, A., Seki, T., Brooker, G., and Spiegel, S. (1991) J. Cell Biol. 114, 155-167). However, little is yet known of the nuclear events that follow the early responses induced by sphingolipid metabolites. Using a gel retardation assay, we found that specific DNA binding activity of activator protein-1 (AP-1) was markedly increased after treatment of quiescent Swiss 3T3 fibroblasts with sphingosine 1-phosphate and sphingosine. The DNA binding specificity of AP-1 was confirmed with competing probes containing consensus sequences of AP-1, AP-2, AP 3, SP-1, and NF1/CTF. The c-fos gene product was detected in the AP-1 complex using anti-c-Fos antibody. The dose response for stimulation of DNA binding activity of AP-1 by sphingosine 1-phosphate correlated closely with its effect on DNA synthesis. Furthermore, an inhibitor of sphingosine kinase, DL-threo dihydrosphingosine, which inhibits sphingosine-induced DNA synthesis and the formation of sphingosine 1-phosphate, also inhibited sphingosine-stimulated AP-1 DNA binding activity. This result further supports our proposal that sphingosine 1-phosphate mediates the mitogenic effect of sphingosine. Our results indicate that sphingosine 1-phosphate-induced DNA synthesis and cell division may result from activation of AP-1 protein, linking signal transduction by sphingolipid metabolites to gene expression. PMID- 8206963 TI - Isolation and characterization of the rat alpha 1(I) collagen promoter. Regulation by vitamin D. PMID- 8206964 TI - Role of membrane anchor domain of Bcl-2 in suppression of apoptosis caused by E1B defective adenovirus. AB - Bcl-2 is an integral membrane protein that functions as a suppressor of programmed cell death. It contains a COOH-terminal signal anchor sequence that is selective for import and insertion of Bcl-2 into the mitochondrial outer membrane and, by a different mechanism, can also direct the protein to other membrane sites. Deletion of the signal anchor sequence rendered Bcl-2 cytosolic and impaired its ability to prevent apoptotic death of human KB cells infected with a mutant form of adenovirus type 5 that does not make E1B 19-kDa protein. When the predicted transmembrane domain of the Bcl-2 signal anchor was replaced with that of the signal anchor of the yeast outer mitochondrial membrane protein, Mas70p, the Bcl-2/Mas70p hybrid was found to be very similar to Bcl-2 in its distribution within transfected KB cells, in its ability to heterodimerize with Bax, and in its ability to suppress apoptosis. These results are consistent with a model in which the transmembrane segment contributes to the function of Bcl-2 by targeting and anchoring the protein to strategic membrane locations in the cell. Concentration of Bcl-2 at these sites may contribute to its proposed role as regulator, or component, of an antioxidant pathway. PMID- 8206965 TI - A G-protein beta gamma-subunit-responsive phosphoinositide 3-kinase activity in human platelet cytosol. AB - Thrombin activates phosphoinositide 3-kinase (PI 3-kinase) in platelets via a mechanism involving G-proteins, possibly of both the heterotrimeric and the low molecular weight families. We have investigated the regulation of PI 3-kinase present in platelet cytosol, and we show that this activity can be stimulated by a mixed preparation of G-protein beta gamma-subunits. This stimulation is reversed by preincubation of the beta gamma-subunits with GDP-liganded alpha subunits. The beta gamma-stimulated activity is inhibited by wortmannin, a recently identified inhibitor of PI 3-kinase in other systems. In addition, the activity associates with PDGF receptor phosphotyrosyl peptide and monoclonal antibody designed to interact with the p85 subunit of PI 3-kinase. We suggest that this beta gamma-sensitive activity is related to previously identified forms of PI 3-kinase. PMID- 8206966 TI - In vitro phosphorylation of the 46-kDa mannose 6-phosphate receptor by casein kinase II. Structural requirements for efficient phosphorylation. AB - Some steps in the receptor-mediated transport of newly synthesized mannose 6 phosphate-containing lysosomal enzymes are assumed to be accompanied by changes in the phosphorylation state of receptors. In vitro, the metabolically phosphorylated 46-kDa mannose 6-phosphate receptor (MPR 46) was dephosphorylated by protein phosphatase 2A. The synthetic cytoplasmic domain of MPR 46 was phosphorylated in vitro by casein kinase II. Tryptic phosphopeptide mapping showed that casein kinase II phosphorylates MPR 46 in vitro at the same site that is phosphorylated in vivo. Inhibition studies using synthetic peptides corresponding to different amino acid sequences of the cytoplasmic tail of MPR 46 revealed that the sequence 26-32 (ADGCDFV) contribute to efficient phosphorylation of serine 56. Baby hamster kidney cells were transfected with wild type human MPR 46 cDNA or cDNAs containing mutations in the cytoplasmic tail and assayed for their phosphorylation state in vivo. The phosphorylation of mutant receptors with deleted residues 23-28 (NLVADG) was strongly reduced. These data indicate that residues on the N-terminal side of the phosphorylatable serine 56 may influence the efficiency with which a casein-kinase II-like kinase phosphorylates MPR 46. PMID- 8206967 TI - Differential structural requirements for specific binding of nonpeptide and peptide antagonists to the AT1 angiotensin receptor. Identification of amino acid residues that determine binding of the antihypertensive drug losartan. AB - The biphenylimidazole derivative losartan exemplifies a novel class of nonpeptide antagonists that selectively inhibit angiotensin II binding to the mammalian AT1 receptor and have potentially wide application as anti-hypertensive agents. In contrast to mammalian AT1 receptors, which have high affinity for both peptide antagonists and losartan, amphibian and avian angiotensin II receptors are pharmacologically distinct and recognize peptide but not nonpeptide antagonists. Mutant rat AT1 receptors in which non-conserved amino acids were replaced by the corresponding amphibian residues were constructed to identify specific sites in the AT1 receptor that determine losartan binding. Only minor changes in binding affinity for peptide antagonists were observed in COS-7 cells transiently expressing mutant receptors, indicating that the structural integrity of the receptor was maintained. However, analysis of receptors with single point and combined mutations revealed that specific residues in transmembrane domains III, IV, V, VI, and VII are involved in binding of the nonpeptide antagonist to the mammalian AT1 receptor. The most marked attenuation of losartan binding (IC50 > 50 microM) was observed in a mutant receptor containing amino acid substitutions at Val108, Ala163, Thr198, Ser252, Leu300, and Phe301. These results have demonstrated that the binding site of a potent nonpeptide antagonist of the AT1 receptor is defined by epitopes located within the membrane-spanning regions of the receptor and is distinct from the site at which peptide antagonists bind to the AT1 receptor. PMID- 8206968 TI - Characterization of surface binding sites for cyclophilin B on a human tumor T cell line. AB - Cyclophilin B (CyPB) is a cyclosporin-binding protein, known to be located mainly within the endoplasmic reticulum vesicles. Its previous characterization in human milk implies that the protein may be released from the secretory pathway and recovered in biological fluids. In an attempt to understand the role of the extracellular CyPB, we have investigated the binding capacity of the protein to cells derived from human T- and B-lymphocytes. We present here evidence that CyPB binds to T-lymphocytes and that the binding to the Jurkat T-cell surface is specific, saturable, and reversible. The dissociation constant Kd was 12 nM, and the number of binding sites was estimated to 35,000/cell. We report that the surface-bound CyPB was internalized at 37 degrees C and subsequently degraded in the cell. We also show that the immunosuppressive drug cyclosporin A does not inhibit the surface binding of CyPB, and does not interfere with internalization of the protein. These results support the hypothesis that the selective action of the immunosuppressive drug results in part from its interaction with the extracellular form of CyPB. PMID- 8206969 TI - Cdc25p, the guanine nucleotide exchange factor for the Ras proteins of Saccharomyces cerevisiae, promotes exchange by stabilizing Ras in a nucleotide free state. AB - In Saccharomyces cerevisiae, adenylate cyclase activity is controlled by Ras1p and Ras2p. Activation of the Ras proteins is in turn controlled by the GTPase activating proteins (GAPs), Ira1p and Ira2p, and the guanine nucleotide exchange factor (GNEF), Cdc25p. We have characterized Cdc25p enzymologically in order to gain information about the mechanism of Cdc25p-mediated guanine nucleotide exchange and to appreciate how the activity of a GNEF is integrated as a part of a basic molecular switch module consisting of Ras, GNEF, and GAP. Using Ras2p and a catalytic fragment of Cdc25p, both expressed in and purified from Escherichia coli, we determined that Cdc25p has a Km for Ras2p-GDP of 160 nM and a maximal rate of 0.20 s-1. The Km of Cdc25p for Ras2p complexed to GTP is 3-fold greater than that for Ras2p complexed to GDP. The Km of free GDP is about 2-fold higher than the Km of free GTP. This suggests that Cdc25p activates Ras2p primarily by equilibrating Ras2p with the pool of free guanine nucleotides in the cell rather than by driving Ras2p inexorably into the activated state. This renders Ras activation potentially subject to energy charge fluctuations in the cell. The free guanine nucleotide affects kcat, indicating that the rate-limiting step is nucleotide association. Finally, we demonstrated that dominant negative alleles of Ras2p are potent competitive inhibitors of Cdc25p. These data, in conjunction with the kinetic data, are consistent with the hypothesis that Cdc25p catalyzes guanine nucleotide exchange by stabilizing a nucleotide-free intermediate of Ras. PMID- 8206970 TI - Activation and release of enzymatically inactive, full-length rhodanese that is bound to ribosomes as peptidyl-tRNA. AB - Synthesis of rhodanese in a cell-free coupled transcription/translation system derived from Escherichia coli leads to an accumulation of full-length rhodanese protein on the ribosomes as well as to enzymatically active protein that is released from the ribosomes into the supernatant fraction. The ribosome-bound protein is enzymatically inactive but can be activated and released from the ribosomes without additional protein synthesis by subsequent incubation in the presence of the added chaperones DnaJ, DnaK, GrpE, GroEL, and GroES plus ATP. Efficient activation requires that all of the chaperones are present together during incubation which yields fully active rhodanese. Incubation in the presence of DnaJ only inhibits release whereas incubation with only GroES or DnaK promotes the release of enzymatically inactive protein. Incubation of the ribosome with puromycin leads to the release of enzymatically inactive protein whereas release and activation in the presence of all of the chaperones is blocked by sparsomycin. The effect of these antibiotics provides very strong evidence that enzymatically inactive, full-length rhodanese is bound to the ribosomes as peptidyl-tRNA and that the peptidyl transferase reaction is required for its release. Considered together, the data indicate that chaperone-mediated late stages of rhodanese folding into the enzymatically active, native conformation are intimately associated with the process of termination and release that occurs as part of the reaction cycle of protein synthesis. PMID- 8206971 TI - Differential activation of adenylyl cyclase by protein kinase C isoenzymes. AB - Cyclic AMP production within cells is altered upon protein kinase C (PKC) activation; however, whether PKC directly modulates adenylyl cyclase (AC) catalytic activity has been controversial. Molecular studies have elucidated the existence of multiple PKC isoenzymes although the functional role of this diversity is not clear. Using purified PKC and AC isoenzymes, we demonstrate that PKC zeta directly phosphorylates type VAC, leading to an approximate 20-fold increase in its catalytic activity, a significantly larger enhancement than that achieved with forskolin (approximately 5-fold), the most potent activator of AC. When forskolin and PKC phosphorylation are combined, type V AC catalytic activity is increased 100-fold over basal levels. The two PKC isoenzymes (alpha and zeta) are additive in their capacity to activate AC, although PKC alpha is less potent than PKC zeta. Our data indicate that PKC can directly and potently regulate AC activity in an isoenzyme-specific manner, suggesting that direct cross-talk plays a major role in coordinating the activity of these two principal signal transduction pathways. PMID- 8206973 TI - Repression of AP-1-stimulated transcription by c-Ets-1. AB - The transcriptional activities of c-Ets-1 and v-Ets and their functional interaction with the AP-1 factor c-Jun were investigated. Several recombinant Ets proteins were produced and purified either from bacteria or from insect cells. Plasmid DNAs that contained the polyoma virus enhancer Ets/AP-1 element were used as templates for in vitro transcription assays in the presence of HeLa nuclear extract and various combinations of the Jun and Ets proteins. Under these conditions full-length c-Ets-1 on its own does not markedly influence transcription but abolishes the strong transcriptional stimulation normally elicited by Jun. This repression depends on the Ets-binding site and on specific features of c-Ets-1 structure, as both v-Ets and a natural splicing variant c-Ets 1 (delta VII) fail to inhibit Jun activity. These findings suggest that c-Ets may act both as a transcriptional repressor or activator depending on promoter context and splicing pattern. PMID- 8206972 TI - Lipoprotein lipase hydrolysis of retinyl ester. Possible implications for retinoid uptake by cells. AB - Adipose tissue contains substantial stores of retinoid (retinol+retinyl ester) that, quantitatively, are second only to retinoid stores in the liver. Our studies show that retinoid levels in adipose tissue are markedly influenced by dietary retinoid intake. Because lipoprotein lipase (LPL) increases the uptake of lipoproteins and lipid emulsion particles by many cell types including adipocytes, we investigated whether LPL also increases retinoid uptake by adipocytes from lipid-containing particles. Addition of LPL (10 micrograms/ml) to BFC-1 beta adipocytes produced a 2-fold increase in cellular uptake of [3H]retinoid from a lipid emulsion containing [3H]retinyl ester. Heparin, which displaces LPL from binding sites on cell surface proteoglycans, increased [3H]retinoid uptake by an additional 2-fold. High performance liquid chromatography analyses showed that greater than 75% of the media and 85% of the cellular radioactivity was present as retinol. The conversion of retinyl ester to retinol by LPL was then assessed using model retinyl ester containing lipid emulsions. Although triglyceride appears to be the preferred substrate for LPL, after greater than 25% of the triglyceride was hydrolyzed, significant amounts of retinyl ester were hydrolyzed by LPL. Retinyl ester hydrolysis was increased approximately 20-fold in the presence of a source of apolipoprotein C-II. The physiologically significant palmitate, stearate, oleate, and linoleate esters of retinol were all hydrolyzed by LPL. When LPL was incubated with [3H]retinyl ester containing rabbit mesenteric chylomicrons and in the presence of heparin and apolipoprotein C-II, the LPL was able to completely hydrolyze the retinyl ester to retinol. Thus, LPL is able to catalyze the hydrolysis of retinyl esters and, through the process of hydrolysis, may facilitate uptake of retinoid by adipocytes. PMID- 8206974 TI - Cbp1p is required for message stability following 5'-processing of COB mRNA. AB - Cbp1p is a nuclear encoded protein required for the stabilization of mitochondrial COB mRNA, which codes for apocytochrome b in the yeast Saccharomyces cerevisiae. The COB gene is cotranscribed with the upstream tRNA(Glu) gene. Release of tRNA(Glu) from the initial transcript generates a precursor mRNA with a 5'-end at position -1098. The 5'-end of mature COB message is generated by cleavage of the pre-mRNA at nucleotide -955 or -954. Previous work indicated that Cbp1p acts through cis-elements near these cleavage sites. Here we have tested whether Cbp1p stabilizes COB mRNA solely by stimulating the processing of COB precursor RNA at nucleotide -955/-954. Yeast strain TG955 was constructed such that the -955 COB mRNA 5'-processing site coincides with the upstream tRNA 3'-endonuclease site at position -1098, allowing the 5'-end of COB mRNA to be formed by the tRNA 3'-processing enzyme. Respiratory growth and stability of COB mRNA in TG955 are Cbp1p-dependent. Therefore, we conclude that Cbp1p is important for the stabilization of COB mRNA after 5'-processing. PMID- 8206975 TI - Bimetallic binding motifs in organophosphorus hydrolase are important for catalysis and structural organization. AB - Organophosphorus hydrolase is a broad spectrum phosphoric acid hydrolase (EC 3.1.8.1) which appears to contain a binuclear metal center with two metals interactively involved in catalysis and/or structural functions. Site-directed mutagenesis has been employed to evaluate the participation of the various histidine and cysteine residues in metal coordination. The kinetic characteristics and metal binding stoichiometries of the purified site-directed substitutions of each of the histidine and cysteine residues in the catalytic domain of the protein to asparagine and serine residues, respectively, were determined. These data support the hypothesis that the histidines at positions 55, 57, and 201 are coordinated to a metal ion (M1) at the active center of the enzyme and that His254 and His257 are involved in the formation of a second structural metal center (M2). These and other unidentified amino acids may participate in a co-catalytic center. Although previous solution chemical studies concluded that cysteines are not involved in metal coordination, serine substitutions for Cys59 and Cys227 do affect metal content and catalytic activity. In contrast, substitution of asparagine for His230 does not affect the metal stoichiometry, but does reduce the kcat by 10(-4), indicating that it may be directly involved in the reaction chemistry. The H201N substitution eliminates activity but maintains one molar equivalent of metal and may function as a bridging ligand. PMID- 8206976 TI - Investigation of the mechanism of glycogen rebound in the liver of 72-hour fasted rats. AB - We have investigated the mechanism of the rebound of glycogen stores in the liver of 72-h fasted rats. The liver of 72- and 96-h fasted rats contains significant amounts of glycogen (about 5 mg/g, wet weight) as compared to the liver of 24- and 48-h fasted rats, which contains less than 2 mg of glycogen/g of liver, wet weight. Rebound of glycogen does not involve glycogen synthase activation or glycogen phosphorylase inhibition. It could be dependent on the concentration of the precursor substrate of glycogenesis, i.e. glucose 6-phosphate (Glc-6-P), which is higher by about 45% in the liver of 72- and 96-h fasted rats than in the liver of 48-h fasted rats. The 72-h increase of Glc-6-P compared with the 48-h values could not be explained either by late modifications of the total activities of glucokinase, hexokinases, Glc-6-P dehydrogenase, and glucose-6 phosphatase (Glc-6-Pase) or by changes in plasma glucose and insulin/glucagon ratio. In agreement with the fact that total glucose output tends to decrease upon prolonged fasting, the increase of Glc-6-P concentration in the liver of 72 h fasted rats suggests the involvement of a metabolite inhibition of Glc-6-Pase. The increase of the alpha-ketoglutarate concentration in the 72- and 96-h fasted liver with regard to the 48-h fasted liver (about three times) might account for such an inhibition since we show here that Glc-6-Pase is inhibited in vitro in the presence of relevant concentrations of alpha-ketoglutarate, Glc-6-P, and Mg2+ ions. PMID- 8206977 TI - Phosphorylation of the erythroid transcription factor GATA-1. AB - GATA-1 is a zinc finger DNA-binding protein thought to be involved in the expression of the vast majority of erythroid specific genes. We have examined the phosphorylation of GATA-1 in murine erythroleukemia (MEL) cells and have mapped the sites of phosphorylation by overexpression of GATA-1 in monkey kidney COS cells. We show that GATA-1 is phosphorylated on 6 serines within its amino terminus in uninduced MEL cells and that a 7th site, serine 310, becomes phosphorylated after MEL cells are induced to differentiate by exposure to dimethyl sulfoxide. This site lies near the carboxyl boundary of the DNA-binding domain in a conserved region of the protein believed to be involved in DNA bending. Detailed analyses indicate, however, that phosphorylation at this site, or the other sites identified, does not significantly influence DNA-binding affinity or specificity, DNA bending, or transcriptional transactivation by GATA 1. PMID- 8206978 TI - Purification and characterization of lipoyl-AMP:N epsilon-lysine lipoyltransferase from bovine liver mitochondria. AB - Lipoyl-AMP:N epsilon-lysine lipolytransferase (lipolytransferase) catalyzes the transfer of the lipoyl group from lipoyl-AMP to a lysine residue of the specific enzyme proteins. We have shown previously that the lipoyltransferase activities locate in mitochondria using apoH-protein of the glycine cleavage system as an acceptor of the lipoyl group (Fujiwara, K., Okamura-Ikeda, K., and Motokawa, Y. (1990) J. Biol. Chem. 265, 17463-17467). Here we describe the purification and the characterization of two isoforms of lipolytransferase termed lipoyltransferase I and lipoyltransferase II from bovine liver mitochondria. Lipoyltransferase II was purified to apparent homogeneity, whereas the final product of lipoyltransferase I still contained a minor contaminant. Although the two forms could be resolved on a hydroxylapatite column chromatography, they were indistinguishable, as judged by: (a) behavior during purification on ion exchange, hydrophobic, or affinity columns; (b) molecular mass determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel exclusion chromatography (40 kDa); and (c) catalytic properties (substrate specificity, kinetic constants, and optimal pH). Both lipoyltransferase I and II could not use lipoic acid plus MgATP as a substrate in place of lipoyl-AMP. Surprisingly, the lipoyltransferases transferred not only the lipoyl group but also the acyl groups from hexanoyl-, octanoyl-, and decanoyl-AMP to apoH-protein to a similar extent. PMID- 8206979 TI - Induction of heat-stable enterotoxin receptor activity by a human Alu repeat. AB - The heat-stable enterotoxins (ST) elaborated by enterotoxigenic Escherichia coli are a family of small cysteine-rich peptides that bind to specific epithelial receptors in the mammalian intestine, causing a secretory diarrhea. The expression of ST receptors is tightly regulated; they are found primarily in intestine, and their expression is developmentally modulated. One receptor for ST has been cloned, and its cDNA encodes a approximately 120-kDa particulate guanylyl cyclase (guanylyl cyclase-C). Recent studies suggest that there are additional ST receptors that are not homologous to guanylyl cyclase-C. We used an expression cloning strategy to identify intestinal mRNAs that lead to expression of ST receptor activity in transfected cells. Using an ST-specific affinity panning system, we identified a novel 1891-base pair cDNA that does not encode a receptor protein, but instead, consists primarily of untranslated sequence. This cDNA induced receptor activity in both COS and 293 embryonic kidney cells. Northern analysis of the T84 human intestinal cell line, from which this cDNA was cloned, suggests that it is part of a 7.8-kilobase mRNA transcript. This transcript was also identified in human small intestine and colon, as well as in several extra-intestinal tissues. Functional analysis of subcloned fragments reveals that ST binding activity is induced by a 457-base pair human Alu repetitive sequence within the cDNA and that the phenotype is independent of orientation. These findings suggest that a human Alu element induces expression of a unique ST receptor by a transacting mechanism. An unrelated Alu-rich genomic clone did not confer ST binding, suggesting that there may be structural and functional specificity within individual Alu sequences. PMID- 8206980 TI - Characterization of a protein that interacts with the rat ribosomal gene promoter and modulates RNA polymerase I transcription. AB - An RNA polymerase I core promoter binding factor (CPBF) was purified to apparent homogeneity from rat adenocarcinoma ascites cells by chromatographic fractionation on a series of columns including an oligodeoxynucleotide affinity column. The final preparation contained two polypeptides with molecular masses of 44,000 and 39,000 daltons. The binding of the factor to the promoter was demonstrated by Southwestern blotting, UV cross-linking and electrophoretic mobility shift assay. The specificity of its binding to the core promoter was confirmed by competitive electrophoretic mobility shift assay using several unlabeled oligo probes in the assay. The addition of increasing amounts of purified CPBF to the in vitro transcription reaction that contains a limiting quantity of the factor resulted in dramatic stimulation of RNA polymerase I (pol I) transcription of rat ribosomal RNA gene. The transcription stimulatory activity associated with the purified CPBF fractions co-purified with the core promoter binding activity in an electrophoretic mobility shift assay. Finally, in a reconstitution transcription system which is devoid of the factor and is incapable of ribosomal gene transcription, purified CPBF could trans-activate the pol I promoter. These data indicate that CPBF is a novel pol I promoter binding factor required for ribosomal gene transcription. PMID- 8206981 TI - S1F binding site is related to but different from the light-responsive GT-1 binding site and differentially represses the spinach rps1 promoter in transgenic tobacco. AB - Nuclear genes encoding plastid ribosomal proteins are more highly expressed in leaves than in roots. This leaf-specific induction seems to be light-independent. We have previously characterized a spinach nuclear factor S1F binding to a cis element within the rps1 promoter, which negatively regulates both the rps1 and the cauliflower mosaic virus 35S promoters in transient expression assays. Here, we show that the S1F binding site is related to but different from the light responsive Box II of the pea rbcS-3A promoter, which is recognized by the nuclear factor GT-1. Transgenic plant analyses showed that the S1F site tissue specifically represses the rps1 promoter in roots as well as in etiolated seedlings. We suggest that the GT-1-related S1F binding site is responsible, at least in part, for the transcriptional repression of rps1 in nonphotosynthetic tissues such as roots. PMID- 8206982 TI - Null thioredoxin and glutaredoxin Escherichia coli K-12 mutants have no enhanced sensitivity to mutagens due to a new GSH-dependent hydrogen donor and high increases in ribonucleotide reductase activity. AB - This work investigates whether a mutator phenotype is associated to the simultaneous deficiency in thioredoxin and glutaredoxin, the two known hydrogen donors of ribonucleotide reductase. To this end, new Escherichia coli K-12 strains carrying delta trxA and/or grx::kan null mutations were constructed to monitor mutagenesis by selecting forward mutations to L-arabinose resistance. Highly sensitive and specific enzyme-linked immunoassays were developed to confirm that trx-grx- cells lacked thioredoxin and glutaredoxin. A number of remarkable properties were observed in the newly constructed thioredoxin- and glutaredoxin-deficient bacteria compared with the wild type cells. Thus, they (i) grew on minimal medium plates, suggesting that the presence of thioredoxin and glutaredoxin may not be absolutely essential for sulfate reduction; (ii) showed normal mutagenic sensitivities toward a wide variety of DNA-damaging agents, as compared with wild type cells and trx- or grx- single mutants; (iii) displayed 14% of GSH-dependent and 30% of NADPH-dependent ribonucleotide reduction capacity with CDP as substrate in the presence or the absence of exogenous ribonucleotide reductase, respectively; and (iv) showed very high levels of ribonucleotide reductase activity, which was increased from 19- to 23-fold. The existence of a new glutathione-dependent hydrogen donor for ribonucleotide reductase and the high activity levels of this enzyme in trx-grx- defective cells could explain that thioredoxin and the first discovered glutaredoxin are not essential for deoxyribonucleotide synthesis, even under mutagenic stress. PMID- 8206983 TI - Inhibition of DnaK autophosphorylation by heat shock proteins and polypeptide substrates. AB - DnaK, the Hsp70 of Escherichia coli, autophosphorylates in vitro. Of the two heat shock proteins that interact with DnaK, GrpE inhibits DnaK phosphorylation, whereas DnaJ has no effect on the reaction. Three synthetic peptides are shown to inhibit DnaK phosphorylation. The potency of a given peptide correlates with its affinity for the DnaK protein. A truncated DnaK that lacks the carboxyl-terminal peptide-binding domain autophosphorylates; this reaction is resistant to the inhibitory peptides. Phosphorylation of the truncated DnaK is still inhibited by GrpE, indicating that the GrpE-binding site resides in the DnaK amino-terminal domain. Thus, DnaK phosphorylation is regulated in vitro, and possibly in vivo, by physiologically relevant substrates and cofactors. PMID- 8206984 TI - A novel synergistic stimulation of Swiss 3T3 cells by extracellular ATP and mitogens with opposite effects on cAMP levels. AB - In Swiss 3T3 mouse fibroblasts, the mitogenic effect of extracellular ATP depends on stimulation of adenylyl cyclase. Lysophosphatidic acid (LPA) and phosphatidic acid (PA) inhibited adenylyl cyclase but synergized with ATP in mitogenic stimulation. This unusual synergism of two mitogens with opposite effects on cAMP levels was further investigated. LPA and PA inhibited the elevation of cAMP caused by cholera toxin, prostaglandin E2, or forskolin, but not the rise induced by ATP. In fact, ATP overcame the inhibitory effects of LPA or PA on cAMP levels. Indeed, in the presence of ATP and either cholera toxin or prostaglandin E2, LPA became a stimulator of adenylyl cyclase. Stimulation of DNA synthesis and inhibition of cAMP accumulation by LPA were inhibited by pertussis toxin, but with different dose-response characteristics. In addition, a normal mitogenic response to LPA was obtained in transfected mutant cells with a defective regulatory subunit for protein kinase A and in cells whose regulation of cAMP levels was abnormal because of overproduction of cAMP phosphodiesterase. The data support the hypothesis that the mitogenic effect of LPA involves a PTX-sensitive Gi protein but not inhibition of adenylyl cyclase. PMID- 8206985 TI - A pK change of acidic residues contributes to cation countertransport in the Ca ATPase of sarcoplasmic reticulum. Role of H+ in Ca(2+)-ATPase countertransport. AB - Proteoliposomal vesicles reconstituted with sarcoplasmic reticulum ATPase and exogenous lipids sustain ATP-dependent Ca2+ uptake and H+ ejection, as well as net charge displacement by Ca2+. We have studied the effect of lumenal (inner) and medium (extravesicular) pH variations on the countertransport ratios of H+ and Ca2+. We find that the Ca2+/H+ molar ratio is approximately 1 when the lumenal and medium pH is near neutrality, but changes with a specific pattern when the medium pH is varied in the presence of a constant lumenal pH and when the lumenal pH is varied in the presence of a constant medium pH. Empirical analysis of the experimental data shows that the apparent pK of the residue(s) releasing H+ into the medium is approximately 6.1, whereas the apparent pK of the residue(s) binding lumenal H+ is approximately 7.7. Assuming that the same acidic residues are involved in H+ and Ca2+ countertransport, our findings suggest a lower affinity for H+ in their outward orientation (prevalent in the ground state of the enzyme) and a higher affinity for H+ in lumenal orientation (prevalent in the phosphorylated state of the enzyme). Cyclic pK changes, coupled to ATP utilization, promote cation exchange, Ca2+ uptake, and H+ ejection by the vesicles. The stoichiometry of countertransport and net charge displacement is matched by a corresponding electrogenic behavior. A calculation of voltage development related to initial rates of charge transfer (dV/dt = (dQ/dt)/Cm) is given as a corrective replacement of a previous steady state calculation. PMID- 8206986 TI - Tissue- and isoform-specific kinetic behavior of the Na,K-ATPase. AB - The objective of this study has been to delineate the side-specific effects of Na+ and K+ on the transport kinetics of tissue-specific Na/K pumps. Two experimental systems have been used. In one, Na/K pumps of exogenous microsomal membrane sources (rat axolemma, kidney) were delivered by membrane fusion into dog erythrocytes, and in the other, the three isoforms of the catalytic subunit of the rat enzyme were individually transfected into HeLa cells as in previous studies (Jewell, E.A., and Lingrel, J. B (1991) J. Biol. Chem. 266, 16925-16930), with the alpha 2 and alpha 3 isoforms rendered relatively resistant to ouabain by site-directed mutagenesis. Whereas the kidney microsomes comprise the alpha 1 catalytic isoform, the axolemma microsomes were predominantly alpha 3 (approximately 60%) with lesser amounts of alpha 2 (approximately 25%) and alpha 1 (approximately 15%) as measured by the ouabain-sensitive profile of phosphoenzyme as well as by immunoblotting with isoform-specific antibodies using membranes of known specific activity as standards (alpha 1 of kidney, alpha 1 and alpha 2 of muscle). Both systems were analyzed with respect to the effects of varying concentrations of cytoplasmic Na+ and extracellular K+ on pump-mediated 86Rb+(K+) influx. With the individual isoform-transfected HeLa cells and monensin added to vary and control the intracellular Na+ concentration, differences in apparent affinities of the alpha 3 isoform compared with the alpha 1 and alpha 2 isoforms were observed, i.e. a approximately 3-fold higher affinity for extracellular K+ and approximately 4-fold lower affinity for cytoplasmic Na+. Thus, in the presence of 10 mM extracellular Na+, apparent K0.5 values for extracellular K+ activation of K+(Rb+) influxes were 0.22 +/- 0.02 mM for alpha 1, 0.20 +/- 0.02 mM for alpha 2, and 0.09 +/- 0.01 mM for alpha 3. At high intracellular K+ (> or = 100 mM) and saturating extracellular K+ concentrations, apparent K0.5 values for cytoplasmic Na+ activation were 17.6 +/- 1.1 mM for alpha 1, 19.7 +/- 1.0 mM for alpha 2, and 63.5 +/- 9.1 mM for alpha 3. The functional differences observed with the individual isoform-transfected cells were completely consistent with the kinetic differences observed with the axolemma and kidney pumps fused into erythrocytes. Axolemma pumps had a approximately 3-fold lower K0.5 for extracellular K+ and a approximately 2-fold higher K0.5 for cytoplasmic Na+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8206987 TI - Effects of mutational loss of nucleoside kinases on deoxyadenosine 5' phosphate/deoxyadenosine substrate cycle in cultured CEM and V79 cells. AB - The functions of a deoxynucleoside kinase and a deoxynucleotidase can give rise to substrate cycles in which the two enzymes catalyze in opposite directions the irreversible interconversion of a deoxynucleoside 5'-monophosphate (dNMP) and its deoxynucleoside. Earlier evidence showed that pyrimidine dNMP cycles occur in cultured cells and participate in the regulation of the size of dNMP pools there by affecting the transport of deoxyribonucleosides across the cell membrane. Here, we apply an isotope flow method using labeled adenine as precursor of dAMP and DNA to quantify deoxyadenosine excretion as a measure of the catabolic activity of a putative dAMP/deoxyadenosine cycle. A comparison of human CEM lymphoblasts and hamster V79 fibroblasts, including mutant cells lacking kinases for the phosphorylation of deoxyadenosine, shows a much lower deoxyadenosine excretion in CEM cells (0.05% of dATP synthesized by reduction of ADP) as compared with V79 cells (4% of dATP). Mutational loss of deoxycytidine kinase increases these values to 0.3% in CEM cells and to 10% in V79 cells. This strongly suggests the presence of a dAMP/deoxyadenosine cycle in both CEM and V79 cells. Additional loss of adenosine kinase only marginally affects deoxyadenosine excretion in CEM cells. The small excretion of deoxyadenosine (also in the absence of both kinases) demonstrates that in CEM cells the in situ activity of the deoxynucleotidase affecting the dAMP/deoxyadenosine substrate cycle is very low and that the cycle has mainly an anabolic function there. PMID- 8206988 TI - DNA-dependent protein kinase is activated by nicks and larger single-stranded gaps. AB - DNA-PK is a DNA-activated serine/threonine protein kinase capable of phosphorylating a number of nuclear DNA-binding proteins. Purified human DNA-PK has two subunits, a 350-kDa polypeptide, Prkdc, which binds ATP and is presumed to contain the catalytic site, and the Ku autoantigen which mediates DNA binding and activation. Previous studies have shown that DNA-PK is activated in vitro by linear double-stranded DNA fragments; however, the Ku subunit binds a broader range of DNA structures. Here we show that EBP-80, a protein originally isolated as a transcription factor for a retroviral long terminal repeat element and subsequently found to be similar to if not identical with Ku, also mediates kinase activation. The EBP-80-Prkdc complex is activated by nanomolar concentrations of DNA constructs containing single-to-double strand transitions, including a closed stem-loop structure and single strand gaps of 0 (nick), 6, and 30 nucleotides. Kinase activation parallels the ability of EBP-80 to bind these and other constructs. Our results extend the range of DNA configurations known to activate DNA-PK and are consistent with the participation of this enzyme complex in several nuclear functions. PMID- 8206989 TI - Binding of 9-cis-retinoic acid and all-trans-retinoic acid to retinoic acid receptors alpha, beta, and gamma. Retinoic acid receptor gamma binds all-trans retinoic acid preferentially over 9-cis-retinoic acid. AB - Both 9-cis-retinoic acid (RA) and all-trans-RA (t-RA) compete for [3H]9-cis-RA binding to RA receptors (RAR alpha, beta, and gamma) in nucleosol fractions from transiently transfected COS-1 cells with IC50 values of approximately 12 and 5 nM, respectively. Curiously, 9-cis-RA competes for [3H]t-RA binding to mouse RAR alpha, beta, and gamma with IC50 values of 31, 8, and 60 nM, respectively, while t-RA itself does not exhibit such differential competition (IC50 values for RARs, 5 nM). A similar pattern is observed with human retinoic acid receptors (RARs). Differential binding of 9-cis-RA to the RAR beta and gamma receptors is also found following in vitro transcription and translation of these receptors. Displacement assays demonstrate that t-RA exhibits similar off-rates for RAR alpha, beta, and gamma. However, 9-cis-RA is 6-fold more rapidly displaced from RAR gamma than from RAR beta. When RAR-transfected COS-1 cells are incubated with [3H]t-RA, [3H]-9-cis-RA or various mixtures of these two radioligands, high performance liquid chromatography analysis demonstrates that the ligands bound in nucleosol fractions from RAR beta-transfected cells reflect the isomer content of the media. However, in identical whole cell assays, nucleosol fractions from RAR gamma-transfected cells preferentially bind t-RA over 9-cis-RA, consistent with the in vitro data. These binding kinetics in vitro and in whole cells suggest that there could be differences in the interactions of the receptor subtypes with the endogenous retinoic acids under physiologic conditions. PMID- 8206990 TI - Mutagenesis of recombinant protein C inhibitor reactive site residues alters target proteinase specificity. AB - Protein C inhibitor (PCI) is a heparin-binding plasma serine proteinase inhibitor (serpin) which is thought to be a physiological regulator of activated protein C. We are using recombinant PCI (rPCI) to study structural determinants of target proteinase specificity. A cDNA encoding full-length PCI has been expressed as a fully active proteinase inhibitor using Autographa californica nuclear polyhedrosis virus (baculovirus). rPCI was expressed maximally 4 days after infection and could be expressed either in Sf9 or High-Five cells. rPCI bound heparin and was conveniently purified with heparin-Sepharose (eluting > 0.5 M NaCl). The rPCI formed sodium dodecyl sulfate-polyacrylamide gel electrophoresis stable complexes with thrombin and activated protein C (APC). The inhibitory properties of wild-type rPCI and plasma-derived PCI are essentially the same either in the absence or presence of heparin with thrombin, APC, trypsin, and urokinase. The residues Phe353-Arg354-Ser355 (P2-P1-P1') constitute part of the reactive site loop of PCI with the Arg-Ser peptide bond being cleaved by the proteinase. Using site-directed mutagenesis we studied the contribution of the reactive site FRS for proteinase inhibition in rPCI. Changing the P1 residue Arg354-->Met generated a reactive site similar to alpha 1-proteinase inhibitor which was a much poorer inhibitor of thrombin, APC, trypsin, and urokinase. Changing the P2 residue Phe353-->Gly generated a mutant with a reactive site like antithrombin which was better at inhibiting thrombin or urokinase, but was much less active with APC or trypsin. Changing the P1' residue Ser355-->Met generated a reactive site like plasminogen activator inhibitor-1 and this protein inhibits all the proteinases essentially like wild-type rPCI. These results show the importance of PCI's Phe353 (P2) and Arg354 (P1) in target proteinase specificity, and they further support the concept of reactive site sequences determining serpin function. PMID- 8206992 TI - Free and albumin-bound bilirubin are efficient co-antioxidants for alpha tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. AB - Peroxidation of the lipid moieties of low density lipoproteins (LDL) is regarded as an early event in atherogenesis. Because bilirubin is a physiological reductant with antioxidant activities, we investigated its inhibitory action on the radical-mediated oxidation of LDL and plasma lipids. Exposing fresh human blood plasma to lipophilic peroxyl radicals generated from 2,2'-azobis(2,4 dimethylvaleronitrile) (AMVN) resulted in rapid oxidation of ubiquinol-10, followed by that of ascorbate and bilirubin. Plasma lipids were well protected from peroxidation as long as these three antioxidants were present, as assessed by the amounts of cholesterylester hydroperoxides formed during this period. Following consumption of these antioxidants, and in the presence of alpha tocopherol, the rate of hydroperoxide formation increased sharply with roughly 2 molecules of cholesterylester hydroperoxides being formed for each peroxidation initiating event. Supplementation of AMVN-oxidizing plasma with exogenous bilirubin at the onset of rapid lipid peroxidation, i.e. after depletion of endogenous ubiquinol-10, ascorbate, and bilirubin, led to a halt in both hydroperoxide formation and consumption of alpha-tocopherol. When isolated LDL was incubated with AMVN, approximately 9 molecules of cholesterylester hydroperoxides were formed per peroxidation initiating event and while alpha tocopherol was consumed. Addition of free or albumin-bound bilirubin to isolated LDL at the onset of oxidation resulted in a strong inhibition of hydroperoxide formation and alpha-tocopherol consumption, the effect being more pronounced with the free pigment. Addition of the corresponding amounts of albumin alone was without effect. In the presence of albumin-bound bilirubin, some 30% of the pigment was initially converted into biliverdin, whereas formation of this oxidation product was not observed with the free pigment. Also, the presence of bilirubin oxidase partially reversed the inhibitory activity of bilirubin on AMVN induced LDL oxidation in the absence but not presence of albumin. An attenuation of hydroperoxide formation and a temporary increase in LDL's alpha-tocopherol concentration were observed when free- or albumin-bound bilirubin were added to AMVN-oxidizing, alpha-tocopherol-containing LDL. In contrast, hydroperoxide formation was not inhibited significantly when the albumin-bound pigment was added to oxidizing LDL after complete consumption of its alpha-tocopherol. Our results show that bilirubin inhibits oxidation of LDL lipids initiated within the lipoprotein core and indicate that this activity is mediated by interaction of the pigment with LDL's alpha-tocopherol. PMID- 8206991 TI - Dual myristylation and palmitylation of Src family member p59fyn affects subcellular localization. AB - The Src family consists of nine related tyrosine protein kinases with a common domain structure, including a myristylated N-terminal glycine residue. In this report, we identify cysteine residues within the N-terminal region of the Src family member Fyn which serve as sites for palmitylation. To facilitate detection of protein fatty acylation, p59fyn was overexpressed in COS cells and incubated with radioiodinated fatty acid analogs of myristate (IC13) or palmitate (IC16). Incorporation of both fatty acids into p59fyn was readily observed. Acylation with the palmitate analog was prevented when Gly-2 was mutated to alanine, implying that N-myristylation is required for palmitylation, and when either Cys 3 or Cys-6 was mutated to serine. Palmitylation was shown to alter the distribution of p59fyn between membrane-bound and soluble fractions. In contrast, no incorporation of the palmitate analog into pp60v-src, which lacks N-terminal cysteine residues, was observed. Mutation of Ser-3 of Src to cysteine, but not Ser-6, resulted in incorporation of the palmitate analog. These results serve to delineate sequence elements important for dual acylation of proteins, and further illustrate the utility of radioiodinated fatty acid analogs for studies of protein fatty acid acylation. PMID- 8206993 TI - 5-Hydroxytryptamine1A receptor synthetic peptides. Mechanisms of adenylyl cyclase inhibition. AB - The 5-hydroxytryptamine1A receptor (5-HT1AR) is a G-protein-coupled receptor negatively coupled to adenylyl cyclase (AC). We have studied the functional domains of 5-HT1AR using synthetic peptides to block or mimic receptor function. The entire second intracellular loop (5-HT1AR-i2) and the carboxyl end of the third intracellular loop (5-HT1AR-i3-C) strongly inhibited forskolin-stimulated AC activity. These effects were not additive with those of 5-HT. Like 5-HT, the peptides 5-HT1AR-i3-C and -i2 weakly inhibited AIF4- and Mn2+ stimulated AC activity. 5-HT1AR binding assays indicated that peptides could interact with the same G-protein pool as the 5-HT1AR. 5-HT1AR-i3-C- and -i2-stimulated [35S]guanosine 5'-O-(thiotriphosphate) binding on Go/Gi proteins. Only 5-HT1AR-i3 C partially adopted an alpha-helical conformation in solution. These data show that different domains in the 5-HT1AR second and third intracellular loops can couple to and activate Gi proteins in order to mediate AC inhibition. Peptide induced AC inhibition was not sensitive to pertussis toxin as opposed to the 5 HT1AR-mediated effect. Our data show that the 5-HT1AR and the 5-HT1AR peptides activate Gi proteins in a slightly different manner. PMID- 8206994 TI - Indolepyruvate ferredoxin oxidoreductase from the hyperthermophilic archaeon Pyrococcus furiosus. A new enzyme involved in peptide fermentation. AB - Pyrococcus furiosus is a strictly anaerobic archaeon that grows optimally at 100 degrees C by a fermentative-type metabolism in which complex peptide mixtures such as yeast extract and Tryptone, and also certain sugars, are oxidized to organic acids, H2 and CO2. Enzymes involved in the utilization of peptides such as proteases, aromatic amino transferases, and glutamate dehydrogenase have been previously purified from this organism. It is shown here that P. furiosus also contains significant cytoplasmic concentrations of a new enzyme termed indolepyruvate ferredoxin oxidoreductase (IOR). This catalyzes the oxidative decarboxylation of aryl pyruvates, which are generated by the transamination of aromatic amino acids, to the corresponding aryl acetyl-CoA. IOR is a tetramer (alpha 2 beta 2) of two identical subunits (66,000 and 23,000 Da) with a molecular weight of 180,000. The enzyme contains one molecule of thiamine pyrophosphate and four [4Fe-4S]2+,1+ and one [3Fe-4S]0,1+ cluster, as determined by iron analyses and EPR spectroscopy. Significant amounts of other metals such as copper and zinc were not detected. IOR was virtually inactive at 25 degrees C and exhibited optimal activity above 90 degrees C (at pH 8.0) and at pH 8.5-10.5 (at 80 degrees C). The enzyme was sensitive to inactivation by O2, losing 50% of its activity after exposure to air for 20 min at 23 degrees C, and was quite thermostable, with a half-life of activity at 80 degrees C (under anaerobic conditions) of about 80 min. The Km values (in microM) for indolepyruvate, p hydroxyphenylpyruvate, phenylpyruvate, CoASH, and P. furiosus ferredoxin, the physiological electron carrier, were 250, 110, 90, 17, and 48, respectively. IOR was inhibited by KCN (apparent Ki = 7.5 mM), but not by CO (1 atm). An enzyme analogous to IOR has not been reported previously. Curiously, it has few properties in common with the pyruvate ferredoxin oxidoreductase of P. furiosus, even though the two enzymes catalyze virtually identical reactions. In fact, of known ketoacid oxidoreductases, the catalytic mechanism of IOR appears to be most similar to that of the pyruvate ferredoxin oxidoreductase from the hyperthermophilic bacterium Thermotoga maritima. PMID- 8206995 TI - A nicotinic acetylcholine receptor ligand of unique specificity, alpha-conotoxin ImI. AB - We report the isolation, characterization, and total synthesis of a small peptide ligand for nicotinic acetylcholine receptors (nAChRs). It is highly active against the neuromuscular receptor in frog but not in mice. In contrast, it induces seizures when injected centrally in mice and rats, suggesting that it may target neuronal nAChRs in mammals. Although such receptors may be important in both normal cognition and the pathophysiology of several neuropsychiatric disorders, there are few ligands to discriminate between the multiple receptor subtypes. The new peptide is a highly divergent alpha-conotoxin from the snail Conus imperialis, which preys on polychaete worms. In this article, the purification, structural analysis, synthesis, and preliminary physiological characterization of alpha-conotoxin ImI (alpha-CTx-ImI) are reported. The sequence of the peptide is: Gly-Cys-Cys-Ser-Asp-Pro-Arg-Cys-Ala-Trp-Arg-Cys-NH2. The peptide shows striking sequence differences from all alpha-conotoxins of fish hunting Conus, but its disulfide-bridging is similar: [2-8; 3-12]. We suggest that cone venoms may provide an array of ligands with selectivity for various neuronal nAChR subtypes. PMID- 8206996 TI - Homeodomain protein MHox and MADS protein myocyte enhancer-binding factor-2 converge on a common element in the muscle creatine kinase enhancer. AB - MHox is a mesoderm-specific homeodomain protein that binds an A/T-rich element that is essential for activity of the muscle creatine kinase (MCK) enhancer. The MHox binding site also binds the ubiquitous homeodomain protein Oct-1 as well as myocyte enhancer-binding factor-2 (MEF2), which belongs to the MADS superfamily of transactivators. To determine which of these proteins activates MCK transcription through the A/T element, we mutated this sequence such that it would selectively bind MHox, MEF2, or Oct-1 and tested the activities of the mutant enhancers in skeletal muscle cells. These mutant enhancers revealed that only MEF2 is able to activate the MCK enhancer through the A/T element. The convergence of homeodomain and MADS proteins on the A/T element in the MCK enhancer provides a mechanism through which a single DNA sequence can mediate positive and negative regulation of gene transcription and is reminiscent of the roles of these two classes of transcription factors in the control of other cell specific genes. PMID- 8206997 TI - Functional human saposins expressed in Escherichia coli. Evidence for binding and activation properties of saposins C with acid beta-glucosidase. AB - Small (80-amino acid) glycoproteins or saposins are important for the in vivo function of several lysosomal hydrolases. Four saposins, A, B, C, and D, are encoded by a single locus termed prosaposin. Saposins C and A are thought to function in vivo as activators of acid beta-glucosidase. The physiologic role of saposin C has been confirmed, whereas that of saposin A role has not. To investigate the effects of saposins C and A on acid beta-glucosidase activity, the coding sequence for the individual saposins was expressed in Escherichia coli and the recombinant proteins purified to homogeneity. Recombinant and natural saposins A and C activated acid beta-glucosidase similarly only in micromolar amounts. Saposin C had specific activation of acid beta-glucosidase activity at < 200 nM. A second phase of activation was achieved at > 1 microM. In comparison, saposin A consistently activated acid beta-glucosidase only at > 1 microM. Two mutant saposins C (Cys382-->Phe and Cys382--Gly) were created and shown to compete with saposin C for a site on acid beta-glucosidase. The mutant saposins did not activate the enzyme. Recombinant saposin A (< 200 nM) competed with saposin C for a site on the enzyme but without activating effects. These studies show that saposin A is not an in vitro activator of acid beta-glucosidase at physiologic concentrations, although binding occurs without activating acid beta glucosidase. The studies with mutant saposins C indicate that the binding and activation effects of saposins C are distinct events. These results indicate that the saposin C-induced conformational change in the enzyme occurs via highly specific, probably multivalent, interactions between acid beta-glucosidase and saposin C. PMID- 8206998 TI - Transforming growth factor-beta response elements of the skeletal alpha-actin gene. Combinatorial action of serum response factor, YY1, and the SV40 enhancer binding protein, TEF-1. AB - Skeletal alpha-actin (SkA) is representative of the cardiac genes that are expressed at high levels in embryonic myocardium, down-regulated after birth, and reactivated by trophic signals including type beta-transforming growth factors (TGF beta). To investigate the molecular basis for cardiac-restricted and TGF beta-induced SkA transcription, we have undertaken a mutational analysis of the SkA promoter in ventricular myocytes, with emphasis on the role of three nominal serum response elements. Serum response factor (SRF) and the bifunctional factor YY1 are the predominant cardiac proteins contacting the proximal SRE (SRE1). Mutations of SRE1 that prevent recognition by SRF and YY1, or SRF alone, virtually abolish SkA transcription in both TGF beta- and vehicle-treated cells; mutation of distal SREs was ineffective. A mutation which selectively abrogates YY1 binding increases both basal and TGF beta-dependent expression, substantiating the predicted role of YY1 as an inhibitor of SRF effects. However, efficient SkA transcription requires combinatorial action of SRE1 with consensus sites for Sp1 and the SV40 enhancer-binding protein, TEF-1. As isolated motifs, either SRE1- or TEF-1-binding sites function as TGF beta response elements. Induction of the SkA promoter by TGF beta required SRF and TEF-1 in concert, unlike other pathways for TGF beta-dependent gene expression. PMID- 8206999 TI - Role of domain 3 of calmodulin in activation of calmodulin-stimulated phosphodiesterase and smooth muscle myosin light chain kinase. AB - CaM[3 TnC] is a calmodulin-cardiac troponin C chimeric protein containing the first, second, and fourth calcium-binding domains of calmodulin (CaM) and the third calcium-binding domain of cardiac troponin C (cTnC) (George, S. E., Su, Z., Fan, D., and Means, A. R. (1993) J. Biol. Chem. 268, 25213-25220). CaM[3 TnC] shows altered activation of phosphodiesterase (PDE) and is a potent competitive inhibitor of smooth muscle myosin light chain kinase (smMLCK) activation by CaM. To determine why CaM[3 TnC] exhibits altered target enzyme interactions, we constructed a series of domain 3 CaM mutants. We began with subdomain substitutions, replacing most of CaM's helix 5, Ca2+ binding loop 3, and helix 6 with the corresponding subdomains of cTnC. Only CaM[helix 6-TnC] exhibited significant impairment of smMLCK and PDE activation. We then individually substituted the residues in the region of CaM's helix 6 with the corresponding cTnC residue. This revealed that CaM residues Thr-110, Leu-112, and Lys-115 were critical for full smMLCK activation and could not be substituted by the corresponding cTnC residue (Gln, Thr, and Thr, respectively). In contrast, only the L112T substitution significantly affected PDE activation. The CaM-smMLCK peptide structure (Meador, W. E., Means, A. R., and Quiocho, F. A. (1992) Science 257, 1251-1255) suggests a relationship between the proposed helix 6 smMLCK activating residues and those previously described in helix 2 (VanBerkum, M. F. A., and Means, A. R. (1991) J. Biol. Chem. 266, 21488-21495). PMID- 8207000 TI - Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. AB - A cDNA coding for a new human matrix metalloproteinase (MMP) has been cloned from a cDNA library derived from a breast tumor. The isolated cDNA contains an open reading frame coding for a polypeptide of 471 amino acids. The predicted protein sequence displays extensive similarity to the previously known MMPs and presents all the structural features characteristic of the members of this protein family, including the well conserved PRCGXPD motif, involved in the latency of the enzyme and the zinc-binding domain (HEXGHXXXXXHS). In addition, this novel human MMP contains in its amino acid sequence several residues specific to the collagenase subfamily (Tyr-214, Asp-235, and Gly-237) and lacks the 9-residue insertion present in the stromelysins. According to these structural characteristics, the MMP described herein has been tentatively called collagenase-3, since it represents the third member of this subfamily, composed at present of fibroblast and neutrophil collagenases. The collagenase-3 cDNA was expressed in a vaccinia virus system, and the recombinant protein was able to degrade fibrillar collagens, providing support to the hypothesis that the isolated cDNA codes for an authentic collagenase. Northern blot analysis of RNA from normal and pathological tissues demonstrated the existence in breast tumors of three different mRNA species, which seem to be the result of the utilization of different polyadenylation sites present in the 3'-noncoding region of the gene. By contrast, no collagenase-3 mRNA was detected either by Northern blot or RNA polymerase chain reaction analysis with RNA from other human tissues, including normal breast, mammary fibroadenomas, liver, placenta, ovary, uterus, prostate, and parotid gland. On the basis of the increased expression of collagenase-3 in breast carcinomas and the absence of detectable expression in normal tissues, a possible role for this metalloproteinase in the tumoral process is proposed. PMID- 8207001 TI - Differential assembly of coexpressed glutamate receptor subunits in neurons of rat cerebral cortex. AB - In the rat, subunits of the glutamate receptor family fall into three pharmacologically distinct groups: alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid preferring receptors (Glu R1-4), kainate preferring receptors (Glu R5-7, KA 1, KA 2), and N-methyl-D-aspartate preferring receptors (NMDA R1, NMDA R2A-2D). In the present study, we demonstrate immunocytochemically that the majority of neurons in rat cerebral cortex coexpress members of all three groups of glutamate receptor subunits, Glu R2/3, Glu R5/6/7, and NMDA R1. Using immunoaffinity purified or immunoprecipitated alpha-amino-3-hydroxy-5-methyl-4 isoxazole propionic acid, kainate and N-methyl-D-aspartate receptors, we show that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors containing Glu R1-4, kainate receptors containing Glu R6, Glu R7, and KA 2 and N methyl-D-aspartate receptors containing NMDA R1 each form distinct protein complexes that do not share subunits. Our data indicate that a mechanism exists which allows for the specific assembly of selected glutamate receptor subunits into functionally and structurally distinct heteromeric receptors. PMID- 8207003 TI - Kinetic and modeling studies of subsites S4-S3' of Moloney murine leukemia virus protease. AB - The substrate specificity of the Moloney murine leukemia virus protease (Mo-MuLV PR) was analyzed by using the oligopeptide substrate Val-Ser-Gln-Asn-Tyr decreases Pro-Ile-Val-Gln-NH2 and a series of analogs containing single amino acid substitutions in the P4-P3' positions. Mo-MuLV PR appears to act similarly to the human immunodeficiency virus (HIV) PRs, except for peptides having substitutions at P4 and P2 positions. Mo-MuLV PR shows a strong preference for the analogs having hydrophobic residues, such as Val or Ile at P4, and Ile and Leu at P2, in contrast to HIV-1 and HIV-2 PRs, which prefer smaller or more polar residues at both positions. We built a molecular model of Mo-MuLV PR on the basis of the crystal structure of the related HIV PR. Although the overall structure of Mo-MuLV PR is predicted to be close to that of HIV-1 PR, almost all of the residues forming the subsites are different. The increased hydrophobicity due to the Pro12 insertion and the presence of more aromatic residues in the S4 subsite of Mo-MuLV PR compared to HIV-1 and HIV-2 PRs can be correlated with the observed differences using P4-substituted analogs of VSQNYPIVQ. The preference of Mo-MuLV PR for larger hydrophobic residues at the P2 position can be correlated with the larger size of its S2 subsite, due in part to the presence of Val39, Ala57, and His84 in Mo-MuLV PR, instead of Ile32, Ile50, and Met76, respectively, as occurs in HIV-2 PR. PMID- 8207002 TI - Molecular cloning of a cDNA encoding a novel human leukocyte alpha-1,3 fucosyltransferase capable of synthesizing the sialyl Lewis x determinant. AB - The sialyl Lewis x determinant (NeuAc alpha 2,3Gal beta 1, 4[Fuc alpha 1,3]GlcNAc) is an essential component of leukocyte counterreceptors for E selectin and P-selectin. The final step in sialyl Lewis x synthesis is catalyzed by alpha-1,3-fucosyltransferases acting on sialylated glycoconjugate precursors. Cultured human leukocytic cell lines express an alpha-1,3-fucosyltransferase gene termed Fuc-TIV or ELFT but do not express the other three cloned human alpha-1,3 fucosyltransferase genes to any significant degree. The physiological role of Fuc TIV/ELFT in sialyl Lewis x biosynthesis is uncertain, however, since it can catalyze the synthesis of this determinant in some, but not all, transfected cell lines in a manner that is dependent upon the glycosylation phenotype of the host cell. We report here the molecular cloning of a cDNA encoding a new human leukocyte alpha-1,3-fucosyltransferase, termed Fuc-TVII, capable of synthesizing the sialyl Lewis x moiety. The cDNA sequence predicts a 341-amino acid-long type II transmembrane protein typical of mammalian glycosyltransferases. When expressed in mammalian cells, the Fuc-TVII cDNA directs the synthesis of cell surface sialyl Lewis x moieties but not the Lewis x, Lewis a, sialyl Lewis a, or VIM-2 determinants. Fuc-TVII can efficiently utilize alpha-2,3-sialyllactosamine in vitro to form the sialyl Lewis x tetrasaccharide but does not utilize lactosamine to form the Lewis x moiety. Northern blot analyses show that the Fuc TVII gene is transcribed in HL-60 cells, a human promyelocytic cell line, and in YT cells, a natural killer-like cell line. Fuc-TVII represents a leukocytic alpha 1,3-fucosyltransferase that can participate in selectin ligand synthesis via its ability to catalyze the synthesis of sialyl Lewis x determinants. PMID- 8207004 TI - Protein kinase C in yeast. Characteristics of the Saccharomyces cerevisiae PKC1 gene product. AB - The Saccharomyces cerevisiae PKC1 gene encodes a homolog of mammalian protein kinase C (Levin, D. E., Fields, F.O., Kunisawa, R., Bishop, J.M., and Thorner, J. (1990) Cell 62, 213-224). A protein of 150 kDa is recognized by a polyclonal antiserum raised against a trpE-Pkc1 fusion protein. In subcellular fractionations, Pkc1p associates with the 100,000 x g particulate fraction. This association is resistant to extraction with high salt concentrations, alkali buffer, or nonionic detergents, suggesting that Pkc1p may be associated with a large protein complex. Pkc1p modified at its COOH terminus with two repeats of the Staphylococcus aureus protein A IgG-binding fragment (ZZ sequence tag) was able to fully restore the growth defects of a pkc1ts strain at restrictive temperature. ZZ-tagged Pkc1p was partially purified by chromatography on DEAE Sepharose, followed by IgG-Sepharose. In vitro, Pkc1p phosphorylates the pseudosubstrate peptide and myelin basic protein, but not histones. Replacing an isoleucine with an arginine 2 amino acids COOH-terminal of the acceptor serine in the substrate peptide resulted in a 10-fold decrease of Km. Pkc1p activity was independent of cofactors such as phospholipids, diacylglycerol, and Ca2+, known to activate several mammalian protein kinase C isoenzymes, making it a rather distantly related member of the protein kinase C superfamily. PMID- 8207005 TI - Saccharomyces cerevisiae PKC1 encodes a protein kinase C (PKC) homolog with a substrate specificity similar to that of mammalian PKC. AB - The PKC1 gene of the budding yeast Saccharomyces cerevisiae encodes a homolog of the alpha, beta, and gamma isoforms of mammalian protein kinase C (PKC) that is essential for cell growth. Loss of PKC1 function results in a cell lysis defect that is due to a deficiency in cell wall construction. In this study, Pkc1p was modified at its COOH terminus with the influenza virus hemagglutinin epitope and was detected by SDS-polyacrylamide gel electrophoresis as a 145- and 150-kDa doublet when overproduced in yeast cells. Pkc1p displayed intrinsic Ser/Thr protein kinase activity in vitro, possessing a substrate specificity similar to that described for mammalian PKC. Specifically, preferred substrates possess an arginine at position -3 and a basic residue at position +2 relative to the target site. A catalytically inactive missense mutant of Pkc1p failed to complement a pkc1 delta mutant, suggesting that protein kinase activity is required for the biological function of Pkc1p. Both wild-type Pkc1p and the inactive form were isolated as phosphoproteins, indicating that Pkc1p is phosphorylated in vivo by another protein kinase. In vitro protein kinase activity of Pkc1p was not dependent on activating cofactors normally required for stimulation of mammalian PKC. However, mutational incapacitation of the pseudosubstrate site of Pkc1p resulted in constitutive activation of the enzyme, both in vivo and in vitro, suggesting that Pkc1p is normally regulated by a mechanism similar to that of its mammalian counterparts. The apparent molecular mass and substrate specificity of Pkc1p, together with its failure to respond to activating cofactors, suggest that this enzyme is distinct from an enzyme purified previously from budding yeast that has enzymatic properties similar to those of mammalian PKC. PMID- 8207006 TI - Farnesyl-L-cysteine analogs can inhibit or initiate superoxide release by human neutrophils. AB - A series of farnesylcysteine analogs was studied with respect to their abilities to interfere with fMet-Leu-Phe (fMLP)-stimulated superoxide (O2-.) release by human neutrophils. Simple acyl derivatives of farnesyl-L-cysteine, such as the N acetyl (L-AFC) and N-isobutyryl derivatives (L-iBFC), which are substrates for the isoprenylated protein methyltransferase, can block O2-. release. The N butyryl analog (L-BFC), which is an isomer of L-iBFC and also a substrate for the methyltransferase, does not inhibit O2-. release but actually stimulates it in the absence of fMLP. Other analogs, including the N-pivaloyl derivative, which has been found to be neither a substrate nor an inhibitor of methyltransferase, also stimulate very large quantities of O2-. production. The stimulatory effects of these derivatives are saturable and exquisitively sensitive to small structural changes in the analogs. The signal transduction pathway(s) utilized by pivaloyl derivatives for triggering O2-. generation is very similar to that employed by fMLP. These data make it clear that farnesyl-L-cysteine analogs do not produce their pharmacological effects in neutrophils via methyltransferase blockade. This could be further demonstrated by showing that sinefungin and S adenosylhomocysteine, both powerful and general methyltransferase inhibitors which bind at the S-adenosylmethionine site, had no effect in preventing the increased oxygen consumption associated with O2-. production in permeabilized neutrophils. These studies reveal that farnesyl-L-cysteine analogs interact with a hitherto undefined target in neutrophils that may be exploited for inhibiting or stimulating the inflammatory or antimicrobial responses of these cells. PMID- 8207007 TI - Molecular cloning of a rat submandibular gland apomucin. AB - Overlapping cDNA clones which encode the protein core of a rat submandibular gland mucin-glycoprotein have been isolated and characterized. Sequence analysis revealed a translated region of 966 nucleotides encoding a protein of 322 amino acid residues. The translational start site begins with a putative signal sequence comprising the initial 22 N-terminal residues. The predicted secreted portion of the apomucin revealed three distinct domains: an N-terminal domain which is enriched in glutamine (14%), proline (13%), and tyrosine (10%); a central region which consisted of eleven, 39-base pair tandem repeats with the consensus sequence PTTDSTTPAPTTK; and a C-terminal domain which is enriched in threonine and serine residues (47%) which are not part of a repeat motif. The expression of apomucin transcript appears restricted to the rat submandibular and sublingual glands. Southern blot analysis of rat genomic DNAs suggested a low copy number (1, 2) for this apomucin gene and a limited polymorphism in the number of tandem repeats. Collectively, our sequence and expression data indicate that the cloned rat submandibular gland apomucin is distinct from any of the other salivary (bovine, porcine, or human) or rat apomucins reported thus far. PMID- 8207008 TI - Alpha A- and alpha B-crystallin in the retina. Association with the post-Golgi compartment of frog retinal photoreceptors. AB - alpha A- and alpha B-Crystallins are significant contributors to maintaining the transparency of the vertebrate lens. We have found that both alpha A- and alpha B crystallins are also present, at approximately equimolar concentrations, in frog retinal cells. They were identified by sequencing portions of each polypeptide, by immunochemical cross-reactivity with antibodies to bovine alpha-crystallins, and by their relative mobility in two-dimensional gel electrophoresis. Retinal alpha-crystallins form macromolecular multimeric complexes similar to those found in the lens, and they are abundant both in soluble and membrane-associated forms. A surprising finding is that alpha-crystallins bind specifically to the photoreceptor post-Golgi membranes that mediate transport of newly synthesized rhodopsin. Upon treatment of post-Golgi membranes with urea or Triton X-114, a portion of the bound alpha B-crystallin remains tightly associated, indicating that the alpha B-form may mediate membrane binding of an alpha-crystallin multimeric complex. Both subunits are synthesized in vitro by isolated frog retinas, but alpha B-crystallin appears to have a higher renewal rate. Newly synthesized alpha-crystallins become associated with the post-Golgi membranes concurrently with newly synthesized rhodopsin. Association of alpha-crystallins with newly synthesized rhodopsin suggests that they may participate in photoreceptor outer segment membrane renewal. Our findings implicate an important function for both alpha A- and alpha B-crystallins in the same, extralenticular, tissue. PMID- 8207009 TI - Phosphorylation of Ser871 impairs the function of His865 of Syrian hamster 3 hydroxy-3-methylglutaryl-CoA reductase. AB - The attenuation of catalytic activity that accompanies phosphorylation of Ser871 of Syrian hamster 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) reflects primarily the introduction of negative charge (Omkumar, R. V., Darnay, B. G., and Rodwell, V. W. (1994) J. Biol. Chem. 269, 6810-6814). To investigate how a negative charge at position 871 attenuates activity, we phosphorylated wild-type and mutant HMG-CoA reductases and assayed reduction of the putative intermediate mevaldehyde to mevalonate. We observed attenuated activity when the phosphorylated wild-type enzyme was assayed in the presence or absence of coenzyme A, but not when assayed in the presence of desthio-CoA. These observations recall the behavior of mutant enzyme H865Q, for which coenzyme A inhibits, whereas desthio-CoA stimulates mevaldehyde reduction (Frimpong, K. F., and Rodwell, V. W. (1994) J. Biol. Chem. 269, 11478-11483). Catalysis of mevaldehyde reduction by mutant enzyme H865Q was unaffected by phosphorylation. By contrast, mutant enzymes H860Q and H868Y, in which nearby, but noncatalytic, histidines had been mutated, exhibited wild-type behavior upon phosphorylation. We conclude that the introduction of negative charge at position 871 impairs the function of His865, presumably by a specific electrostatic interaction. We propose a novel mechanism by which phosphorylation regulates activity. Phosphorylation of the terminal serine of the consensus AGxLV(K/R)SHMxxNRS motif of eukaryotic HMG-CoA reductases attenuates activity by impairing the ability of the catalytic histidine to protonate the CoAS- anion formed during the reductive deacylation of HMG-CoA to mevaldehyde. PMID- 8207010 TI - Basolateral targeting and efficient consumption of transforming growth factor alpha when expressed in Madin-Darby canine kidney cells. AB - To investigate the trafficking of transforming growth factor-alpha precursor (pro TGF-alpha) in polarized epithelial cells, wild type and membrane-fixed human pro TGF-alpha were introduced into Madin-Darby canine kidney (MDCK) cells. We show that wild type pro-TGF-alpha was synthesized and processed normally to release mature 5.6-kDa TGF-alpha into the basal medium while membrane-fixed pro-TGF-alpha remained cell-associated. Antibody (mAb-528) receptor blockade experiments demonstrated the efficient consumption of basally released TGF-alpha by basolateral epidermal growth factor receptors, indicating that TGF-alpha can act in an autocrine manner in these polarized epithelial cells. Biochemical analysis showed pro-TGF-alpha was expressed on the basolateral surface as either a 17- or 30-kDa species; the 17-kDa forms of both pro-TGF-alpha constructs had basolateral/apical ratios of > 20:1. By confocal microscopy, membrane-fixed pro TGF-alpha was immunolocalized to lateral membrane surfaces. In pulse-chase experiments combined with cell surface immunoprecipitation, we demonstrated that newly synthesized wild type and membrane-fixed pro-TGF-alpha are delivered directly to the basolateral surface with 94 and 96% efficiency, respectively. These results also provide direct evidence for sequential cleavage of pro-TGF alpha at the basolateral membrane surface. Thus, pro-TGF-alpha is sorted intracellularly and vectorially targeted to the basolateral membrane domain in these polarized epithelial cells. The MDCK cell line provides an ideal in vitro model to examine the molecular basis for trafficking of pro-TGF-alpha and other epidermal growth factor-like growth factors in polarized epithelial cells and their potential interactions with basolateral epidermal growth factor receptors. PMID- 8207011 TI - Activation of the multicatalytic protease. The 11 S regulator and 20 S ATPase complexes contain distinct 30-kilodalton subunits. AB - The multicatalytic protease (MCP) associates with a 20 S ATPase complex in the presence of ATP to form the 26 S ubiquitin/ATP-dependent protease. This association results in a uniform 3-fold activation of peptide hydrolysis by MCP. In the absence of nucleotides, an 11 S regulator binds MCP and differentially stimulates its peptidase activities from 3-fold to 25-fold depending upon the peptide. When incubated separately with ATPase complex or regulator, all MCP molecules are converted to 26 S protease or to an activated MCP, respectively. Competition between ATPase complex and regulator for limiting amounts of MCP results in the 26 S protease as the only assembled species. Rabbit reticulocyte regulator is composed of a single 30-kDa protein. Among the 15 subunits in the ATPase complex, there is also a 30-kDa protein. Three findings demonstrate that the 30-kDa subunits in each complex are distinct proteins. First, two-dimensional polyacrylamide gel revealed different isoelectric points for each 30-kDa protein. Second, anti-regulator antibodies did not cross-react with proteins in the ATPase complex or in the 26 S protease. Third, directly sequenced peptides from the 30 kDa subunit of the ATPase complex are not present in the deduced amino acid sequence of the regulator. Thus, the regulator and ATPase complex are independent activators of MCP. PMID- 8207012 TI - Effect of cadmium on estrogen receptor levels and estrogen-induced responses in human breast cancer cells. AB - The effects of cadmium on estrogen receptor and other estrogen-regulated genes in the human breast cancer cell line MCF-7 were studied. Treatment of MCF-7 cells with 1 microM cadmium decreased the level of estrogen receptor 58%. Cadmium induced a parallel decrease in estrogen receptor mRNA (62%). Progesterone receptor levels increased 3.2-fold after cadmium treatment. This induction was blocked by the anti-estrogen ICI-164,384. Progesterone receptor mRNA was also increased by cadmium, as well as cathepsin D mRNA. An in vitro nuclear transcription run-on assay showed that cadmium increased the transcription of the progesterone receptor and pS2 genes and decreased transcription of the estrogen receptor gene. These are not general effects of heavy metals, as zinc, 25 and 100 microM, did not affect progesterone receptor protein and mRNA levels. Cadmium stimulated pS2 and progesterone receptor mRNAs in a clone of MDA-MB-231 cells transfected with the human estrogen receptor, but had no effect in MDA-MB-231 cells transfected with antisense estrogen receptor. Cadmium also stimulated an estrogen response element in transient transfection experiments. These data suggest that the effects of cadmium are mediated by the estrogen receptor independent of estradiol. In addition to its effect on gene expression, cadmium induced the growth of MCF-7 cells 5.6-fold. PMID- 8207014 TI - Structural analysis and functional role of the carbohydrate component of glycine transporter. AB - The sodium- and chloride-coupled glycine transporter from pig brain stem has been shown to be a 100-kDa glycoprotein (Lopez-Corcuera, B., Vazquez, J., and Aragon, C. (1991) J. Biol. Chem. 266, 24809-24814). To structurally identify the carbohydrate components of glycine transporter, the purified and radioiodinated protein was subjected to specific glycosidase treatments. When the glycine transporter was treated with peptide-N-glycosidase F (PNGaseF) to remove N-linked oligosaccharides, a significant reduction of the apparent molecular mass of the protein was observed. However, incubations with endoglycosidase F and O-glycanase did not affect the electrophoretic mobility of the protein, and neuraminidase produced a slight reduction of its apparent mass. The effect of PNGaseF indicates that sugar chains represent about 30% of the mass of this heavily glycosylated transporter. The deglycosylated form is recognized by previously characterized anti-100-kDa protein antiserum (Lopez-Corcuera, B., Alcantara, R., Vazquez, J., and Aragon, C. (1993) J. Biol. Chem. 268, 2239-2243), suggesting that the epitopes are in the peptidic part of the glycoprotein. These and other results suggest that glycine transporter-linked carbohydrates are predominantly tri- or tetra- antennary complex N-linked oligosaccharides containing sialic acid residues. To investigate the functional role of the carbohydrate moiety, liposomes reconstituted with purified glycine transporter were subjected to PNGaseF and neuraminidase treatments, and the effect on specific glycine transport activity was tested. Whereas neuraminidase did not affect the activity of the transporter, PNGaseF treatment produced a drastic reduction of transport activity. This treatment produced two different deglycosylated glycine transporter species, suggesting that two N-glycosylation sites would be occupied in the native protein. These studies arise as a first evidence supporting the notion that N-linked carbohydrates play a relevant role in glycine transporter functionality. PMID- 8207013 TI - Topological analysis of H+,K(+)-ATPase using in vitro translation. AB - The membrane topology of the alpha subunit of the H+,K(+)-ATPase was investigated by using in vitro transcription/translation of DNA sequences encoding fusion proteins that contained possible membrane-spanning segments. The vectors consisted of DNA sequences encoding (a) either the first 101 (M0 vectors) or the first 139 (M1 vectors) amino acids of the N-terminal region of the alpha subunit of the ATPase, (b) a variable region, and then (c) the C-terminal 177 amino acids of the C-terminal region of the beta subunit, with five N-linked glycosylation sites. The variable region of the fusion protein contained the cDNA sequences representing the possible eight or 10 membrane-spanning segments either alone or in various combinations. Transcription/translation was performed in the presence of [35S]methionine using a coupled reticulocyte lysate in the absence and presence of microsomes. The fusion protein was identified by autoradiography following separation using SDS-polyacrylamide gel electrophoresis. Glycosylation of a translated sequence corresponded to membrane insertion and translocation of the C-terminal beta sequence. This method allowed analysis of signal anchor sequences using the M0 vector. The presence of a stop transfer sequence in the variable segment of the M1 vector resulted in inhibition of translocation of the C-terminal beta sequence. The sequences for the first four membrane segments could act as either signal anchor or stop transfer sequences. Therefore, this region of the alpha subunit has four membrane-spanning segments that are co inserted with translation. The sequence corresponding to membrane segment M8 acted as a stop transfer sequence. The sequence corresponding to membrane segment M9 acted as a signal anchor sequence, and that corresponding to membrane segment M10 acted as a stop transfer sequence. The sequences representing the fifth, sixth, and seventh (M5, M6, and M7) membrane segments were unable to co-insert into the membrane. These data verify the first four and the eight membrane spanning segments of the alpha subunit of the gastric H+,K(+)-ATPase and provide evidence for translational insertion of an additional pair of membrane-spanning segments, M9 and M10. It appears that insertion of membrane segments M5, M6, and M7 is determined differently from the other membrane-spanning segments. In combination with other methods, this in vitro transcription/translation method is useful for defining the membrane topology of the P type ATPases. PMID- 8207015 TI - Characterization of thrombomodulin expression in response to retinoic acid and identification of a retinoic acid response element in the human thrombomodulin gene. AB - Thrombomodulin (TM) is an essential cofactor for the physiologic activation of the anticoagulant protein C by thrombin. We have observed that the expression of TM mRNA in response to retinoic acid was markedly increased in human U937 monoblast-like cells, and human MEG01 megakaryocyte-like cells, but not in human umbilical vein cells, murine hemangioma cells, human K562 erythroblast-like cells, and murine HSD fibroblast-like cells. TM activity in U937 cells and MEG01 cells was not detectable in untreated cells, but developed rapidly after treatment with retinoic acid. In endothelial cells there was minimal change in TM activity in response to retinoic acid treatment. We have isolated clones for the genes for murine and human TM and have identified potential retinoic acid response elements in the 5'-flanking region of the human gene. In U937 cells the increase in mRNA levels was associated with increased transcription, and transient transfection studies with reporter plasmids demonstrate functional retinoic acid response elements present in the 5'-flanking region of the gene. Deletion of, and mutations introduced into, the potential retinoic acid response element confirm the functional response in transient transfections. PMID- 8207016 TI - Reversible inhibition of gene expression by a psoralen functionalized triple helix forming oligonucleotide in intact cells. AB - Triple helix formation of nucleic acids is the most rational approach to designing site-specific transcription inhibitors. To increase their efficiency, reactive moieties such as psoralen or ethenocytosine have been introduced on the third strand. In transfected cells, these compounds induce a site-specific covalent binding of the third strand to the targeted sequence and efficiently block RNA polymerases. However, the stability of this transcription inhibition has never been checked. We have designed a plasmid containing a triple helix binding site in the coding region of the beta-galactosidase reporter gene and a polymerase chain reaction assay to follow quantitatively the cross-link of a psoralen-derivatized third strand in transfected cells. This assay has revealed that the cross-link was removed within a few hours, leading only to a transitory inhibition of gene expression. Control experiments in DNA repair-deficient cells suggest the implication of repair enzymes in this process. PMID- 8207018 TI - Rat natural killer cell antigen, NKR-P1, related to C-type animal lectins is a carbohydrate-binding protein. AB - Natural killer receptor protein 1 (NKR-P1, a family of proteins), which is a dimeric transmembrane protein predominantly on rat and murine natural killer cells, contains an extracellular motif related to calcium-dependent animal lectins. The domain architecture of this protein and the finding that its cross linking with antibody results in activation of natural killer cells make it a promising candidate for a receptor function. We have expressed a full-length NKR P1 protein of the rat in COS cells and prepared soluble extracellular fragments by controlled proteolysis or by expression of truncated cDNA in bacteria. Dimerization of soluble NKR-P1 is predominantly dependent on the presence of an intact juxta-membrane stalk region and independent of N-glycosylation. Binding and inhibition studies using monosaccharides and neoglycoconjugates indicate that NKR-P1 is a lectin with a preference order of GalNAc > GlcNAc >> Fuc >> Gal > Man. At neutral pH, Ca2+ is tightly associated with the protein such that only a proportion can be removed by 10 mM EGTA. However, NKR-P1 can be decalcified completely at pH 10 with a total loss of carbohydrate binding. After recalcification at pH 8, carbohydrate binding is completely restored. Thus, NKR P1 differs from other calcium-dependent animal lectins investigated so far in its pattern of monosaccharide recognition and in the tightness of Ca2+ binding. PMID- 8207017 TI - Differential regulation of protein kinase C isoforms in isolated neonatal and adult rat cardiomyocytes. AB - We have immunologically identified the isoforms of protein kinase C (PKC) present in neonatal and adult rat cardiomyocytes and examined their regulation by hormones and phorbol ester. Both cell types express the Ca(2+)-dependent alpha PKC and the Ca(2+)-independent epsilon- and delta-PKC isoforms. The atypical zeta PKC isoform is also expressed in neonatal, but only weakly in adult cells. Stimulation of the alpha 1-adrenergic or purinergic receptor with phenylephrine or ATP, respectively, increases membrane-associated immunoreactivity of both epsilon- and delta-PKC in neonatal and adult cells; endothelin and carbachol are also effective in adult cells. In contrast, none of the agonists leads to increases in membrane-associated alpha-PKC in cardiomyocytes. PKC zeta is also unaffected by receptor stimulation. The phorbol ester phorbol 12-myristate 13 acetate causes redistribution and subsequently down-regulation of alpha-, epsilon , and delta- but not zeta-PKC. The three isoforms are down-regulated at distinctively different rates, with alpha-PKC being the most rapid and epsilon PKC the slowest. We used selective down-regulation of alpha-, epsilon-, and delta PKC to investigate the role of these isoforms in PKC phosphorylation-dependent events in neonatal myocytes. Our findings suggest that epsilon-PKC is responsible for the phenylephrine-induced phosphorylation of MARCKS, an endogenous PKC specific substrate. In contrast, agonist-induced c-fos expression is unlikely to be mediated by epsilon-PKC since the response is rapidly down-regulated and apparently Ca(2+)-dependent. Our finding that the PKC isoforms are differentially responsive to neurohormones suggests that they play distinct and specific roles in cardiac function. PMID- 8207019 TI - Evidence for NH2- and COOH-terminal interactions in rat 6-phosphofructo-2 kinase/fructose-2,6-bisphosphatase. AB - The pH kinetic behavior of several rat fructose-2,6-bisphosphatase forms was analyzed. The bisphosphatase maximal velocity of the hepatic 6-phosphofructo-2 kinase/fructose-2,6-bisphosphatase was optimal at pH 5, but decreased to 12% of the optimal value in the pH range 7.0-7.5. This decrease depended on deprotonation of a group with a pK of 5.7. In contrast, the separate bisphosphatase domain, a 30-amino acid COOH-terminal truncated form (CT30) of the liver enzyme, and the skeletal muscle bifunctional enzyme exhibited pH insensitive maximal velocities which were 5-10-fold higher than that of the bisphosphatase of the liver bifunctional enzyme at pH 7.0-7.5. The pK values of the C-2 and C-6 phosphoryl groups were 6.0 and 5.75, respectively, as determined by 31P NMR. Analysis of log kcat/Km versus pH profiles revealed two pK values, one at 6.1, which probably is a substrate pK, and the other at 8.4, which represents an enzyme group. Protein kinase-catalyzed phosphorylation of the liver isoform activated the bisphosphatase, and the pK of the group seen in the kcat profile was increased from 5.7 to 6.4. However, phosphorylation of the CT30 mutant had no effect on the bisphosphatase. The data indicate that NH2- and COOH terminal interactions in the liver bifunctional enzyme affect the pH dependence of the fructose-2,6-bisphosphatase and its activation by phosphorylation. PMID- 8207020 TI - Chamber specification of atrial myosin light chain-2 expression precedes septation during murine cardiogenesis. AB - To study the molecular mechanisms that control patterning of the heart tube during early cardiogenesis, we have used the ventricular myosin regulatory light chain (MLC-2v), which is expressed in the ventricular segment of the primitive heart tube, as a genetic marker for ventricular specification in rodents. To assess whether the atrial isoform, MLC-2a, could also serve as a chamber-specific marker, we cloned an atrial MLC-2 cDNA (554 base pairs) which displayed homology to the human MLC-2a cDNA at both the nucleotide (87%) and amino acid (95%) levels. Northern blot, reverse transcriptase-linked polymerase chain reaction, RNase protection, and Western blot analysis revealed atrial restricted expression in the adult mouse heart, very low levels in aorta, and no detectable expression in ventricle, skeletal muscle, uterus, or liver. In situ hybridization studies during mouse embryogenesis revealed cardiac specific expression throughout days 8 16 postcoitum, with atrial restricted expression from day 12 and qualitatively greater atrial expression than ventricular from day 9. Thus, preferential pattern of expression in the atria occurs prior to septation. The MLC-2a gene was differentially regulated when compared with MLC-2v expression during embryonic stem cell cardiogenesis in vitro with MLC-2a transcript levels detectable from day 6 in suspension cultures as compared with day 9 for MLC-2v. The region specific expression of the MLC-2a and MLC-2v genes in their respective chambers during early cardiogenesis provides genetic markers for chamber specification (atrial and ventricular) in both the in vitro and in vivo context. PMID- 8207021 TI - Novel human glutamate dehydrogenase expressed in neural and testicular tissues and encoded by an X-linked intronless gene. AB - Glutamate dehydrogenase, an enzyme central to glutamate metabolism, is deficient in patients with heterogeneous neurological disorders characterized by multiple system atrophy. There is evidence for multiplicity of human glutamate dehydrogenase, which may account for the heterogeneity of the above disorders. However, only one mRNA that is encoded by an intron-containing gene (GLUD1) is presently known. Because blindness due to neuroretinal degeneration can occur in rare forms of multiple system atrophy, we searched for retina-specific GLUD mRNA(s) by screening a lambda gt10 library derived from human retina. A novel cDNA encoded by an X chromosome-linked intronless gene, designated GLUD2, was isolated and characterized. Reverse transcription-polymerase chain reaction analysis of human tissues revealed that the novel cDNA is expressed in human retina, testis, and, at lower levels, brain. In vitro translation of mRNAs derived from GLUD1 and GLUD2 genes generated proteins with distinct electrophoretic characteristics. The retinal cDNA was expressed in the baculovirus heterologous system, producing a protein capable of catalyzing the oxidative deamination of glutamate. The mobility of the expressed protein on SDS polyacrylamide gel electrophoresis and its catalytic properties were very similar to those of the naturally occurring human brain glutamate dehydrogenases. The novel gene will be useful for understanding the biology of human neural and testicular tissues and in the study of X-linked neurodegenerative disorders. PMID- 8207022 TI - Subunit composition and domain structure of the Spo0A sporulation transcription factor of Bacillus subtilis. AB - The Spo0A transcription factor is responsible for the initiation of sporulation and is active in transcription only after phosphorylation by a specific signal transduction pathway, the phosphorelay. The effect of phosphorylation on the physical properties of Spo0A was determined. Spo0A and Spo0A approximately P both behaved as monomers during Sephacryl chromatography and gel electrophoresis, suggesting that phosphorylation did not modify the oligomerization state of the protein. Trypsin digested Spo0A at a single cleavage site between residues 142 and 143 within a hinge connecting two tightly folded domains. The amino domain retains ability to be phosphorylated by the phosphorelay. The carboxyl domain is active as a DNA-binding protein and retains the sequence specificity of the intact molecule for 0A boxes on the abrB promoter as revealed by footprinting studies. The carboxyl domain stimulated in vitro transcription from the spoIIG promoter 5-fold greater than an equal amount of Spo0A and about half as well as equivalent amounts of Spo0A approximately P. Thus, the unphosphorylated amino domain inhibits the transcription stimulation activity of the carboxyl domain. We suggest that phosphorylation activates transcription regulation functions of Spo0A by modifying the spatial relationships of the amino and carboxyl domains. PMID- 8207023 TI - Isolation and characterization of cDNA clones for chloroplast translational initiation factor-3 from Euglena gracilis. PMID- 8207024 TI - Interface reactions to PEO/PBT copolymers (Polyactive) after implantation in cortical bone. AB - The bone reaction at the interface of a range of PEO/PBT copolymers (Polyactive) after press-fit implantation in the diaphyseal femur of 20 goats was investigated. The animals were sacrificed at 1, 4, 12, 26, and 52 weeks. Undecalcified histologic sections were prepared, evaluated qualitatively, and quantified with the aid of an image analysis system. The percentage of bone contact was determined morphometrically for all PEO/PBT proportions; for the 70/30 ratio, the percentage of calcification of the material surface and of bone bonding (defined as a continuum at the light microscopic level between calcification within the material surface and bone tissue) were also assessed. PEO/PBT copolymers possess hydrogelic properties, and a direct relation has been established between water-uptake and PEO content. The swelling behavior of all PEO/PBT substrates resulted in a high degree of bone contact (over 95%) at early stages. From the 12-week survival time onward the 70/30 revealed higher percentages of bone contact (over 80%) when compared with the other ratios (60/40, 55/45, 40/60, and 30/70). This difference was statistically confirmed 1 year postoperatively. The materials with the higher PEO contents showed the highest amounts of calcification, which is reflected by the rate of bone-bonding (70% of bone-bonding for the 70/30 at 52 weeks). Calcification and bone-bonding were not observed for 40/60 and 30/70 proportions. The quantitative results confirmed the relation between PEO content, water-uptake, calcification, and bone bonding. It was furthermore demonstrated that PEO/PBT copolymers initially establish a high degree of bone contact, whereas the bone-bonding properties, especially of the 70/30, accomplish a long-term implant fixation. PMID- 8207025 TI - Application of flow cytometry to determine the cytotoxicity of urethane dimethacrylate in human cells. AB - The effects of an oligomer, urethane dimethacrylate (UDMA), on two human cell lines were studied using flow cytometry (FCM). Untreated and treated cultures of propidium iodine-stained KB (epidermal oral carcinoma cells) and human foreskin fibroblast (HFF) cells were analyzed for cellular DNA content. Concentrations of 10 and 25 microM of UDMA slightly perturbed the KB cell cycle progression at 24 and 48 h of incubation. However, the effect of 50 microM was more pronounced at the latter incubation time period. In cell growth experiments, the sublethal concentrations (10 and 25 microM) produced inhibition of KB cell growth rate at a moderate level, which resulted in the prolongation of cell population doubling time. Significant inhibition of cell growth occurred when 50 microM (lethal concentration) was used. Data obtained from the cell cycle perturbation analysis, evidenced by FCM, correlated with the extent of inhibition in KB cell growth rates. The effects of sublethal concentrations were reversible during a 24 h period of oligomer withdrawal from culture medium. In contrast, the effects of 50 microM were not reversible. In HFF cells the depletion of S phase in the cell cycle was the major effect of 50 microM of UDMA. It was concluded that FCM technology is an ideal and practical approach for studying the cytotoxicity of components of dental composites. PMID- 8207026 TI - Use of diphenylphosphorylazide for cross-linking collagen-based biomaterials. AB - Cross-linking of collagen-based biomaterials increases their strength and persistence in vivo. Recently, we described an efficient cross-linking process via the formation of acyl azide groups on methylated carboxyl groups of collagen using hydrazine and nitrous acid (referred to here as the hydrazine method). In this report, we propose a simpler, faster way to prepare acyl azide groups and to cross-link collagen-based biomaterials, using diphenylphosphorylazide (DPPA) as a reagent. After determining the optimal conditions of cross-linking with DPPA, we compared the efficiency of this protocol with that using hydrazine and with the classical glutaraldehyde treatment. In order to validate and quantitate the extent of reaction, the degree of cross-linking was determined by the measure of the free primary amino group content of the samples. Treatment of native bovine pericardium with 0.5% DPPA for 24 h led to efficient cross-linking, corresponding to a 50% decrease in the free primary amino group content of the sample and raising its thermal stability from 62.8 up to 81.3 degrees C. In comparison, the thermal stabilities of glutaraldehyde or hydrazine-treated pericardium were 85 +/ 0.4 degrees C and 83.4 +/- 0.1 degrees C. Similar decreases in free primary amino group content and increases in thermal stability were obtained for collagen films treated with DPPA, glutaraldehyde, or hydrazine. These results were corroborated by resistance to bacterial collagenase digestion: DPPA-treated pericardium had a resistance to collagenase digestion similar to that of glutaraldehyde- or hydrazine-treated pericardium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207027 TI - Screening of matrices and fibers for reinforced thermoplastics intended for dental applications. AB - Plastics reinforced with continuous fibers (FRC) are being developed for dental applications, such as prosthodontic frameworks and orthodontic retainers. Flexure properties, stress relaxation and hydrolytic stability of FRC based on six thermoplastic matrices, three types of fibers, and three fiber volume fractions were evaluated. Samples with clinically relevant dimensions were tested. Polycarbonate was the preferred matrix material. Polycarbonate reinforced with 42 volume percent glass fibers exhibited the highest combination of flexure modulus (17.9 +/- 2.6 GPa), flexure strength (426 +/- 40 MPa), reinforcing efficiency (0.79), and resistance to stress relaxation. No statistically significant difference was observed between E and S2 glass reinforced composites under the experimental conditions used. Kevlar reinforced materials exhibited a low flexure modulus and strength. The apparent flexure moduli of all composites decreased with span length in the range of clinical interest. Generally, the prevalent mode of failure for all FRC investigated was brittle failure under flexure loading. Relatively large sample-to-sample variation in both composition and properties indicated that improved fabrication methods will be needed in future studies. The combination of good flexure properties, formability, and translucency suggests that novel appliance designs for dentistry are feasible with FRC, but further studies of its properties and particularly the effects of fiber/matrix interfacial quality are needed. PMID- 8207028 TI - Elutions of metal ions from dental casting alloys and their effect on calcium phosphate precipitation and transformation. AB - The elution characteristics of metal ions from dental casting alloys were studied in vitro. Large amounts of nickel (0.12-4.94 mg/cm2) and chromium (< 0.01-0.63 mg/cm2) were solubilized from the surface of seven brands of nickel-chromium alloy in either 1% lactic acid or 0.05% hydrochloric acid solutions. The elution of chromium from two brands of cobalt-chromium alloys in both eluents was below the detection limit or less than 0.01 mg/cm2. The elution of tin, copper, and zinc from a gold-palladium-silver alloy in both eluents was below the detection limit or less than 0.01 and 0.04 mg/cm2. Some amounts of tin (0.19-1.92 mg/cm2) and zinc (0.56-1.73 mg/cm2) were eluted from a silver alloy in both eluents. The effects of five eluting metal ions, i.e., nickel, chromium, tin, copper, and zinc, on the conversion of amorphous calcium phosphate (ACP) to hydroxyapatite (HAP) in vitro also were studied by a pH drop method. All divalent cations except for chromium decreased the rate of HAP transformation and elongated the induction time. Nickel had an inhibitory effect comparable to 1-hydroxyethylidene-1, 1 bisphosphonate (HEBP) on the rate of HAP transformation. Tin, copper, and zinc inhibited similarly, but the inhibition was weaker than that by nickel. Chromium did not inhibit these reactions. PMID- 8207029 TI - Fatigue crack propagation behavior of ultra high molecular weight polyethylene under mixed mode conditions. AB - Analytical studies of the stresses on and within ultra high molecular weight polyethylene joint components suggest that damage modes associated with polyethylene fatigue failure are caused by a combination of surface and subsurface crack propagation. Fatigue crack propagation tests under mixed mode loading conditions were conducted on center-cracked tension specimens machined from extruded blocks of sterilized polyethylene in an attempt to determine how fatigue cracks change direction in this material. Cyclic testing was performed using a sinusoidal wave form at a frequency of 5 Hz and an R-ratio (minimum load/maximum load) of 0.15. Specimens had the notch oriented perpendicular to the direction of applied load and at angles of 60 degrees and 45 degrees to the loading direction. Numerical analyses were used to interpret the experimental test and to predict the fatigue behavior of polyethylene under mixed mode conditions. It was found that all cracks eventually propagated horizontally, regardless of the initial angle of inclination of the notch to the direction of applied cyclic load. In fact, the extent of the curvilinear crack growth was quite limited. An effective range of cyclic stress intensity factor was calculated for correlation with the rate of crack growth. The results followed a Paris relation, with crack growth rate linearly related to a power of the range of stress intensity, for all three crack orientations. The numerical analyses adequately modeled the experimental fatigue crack growth results. PMID- 8207030 TI - Thermal shock resistance of core reinforced all-ceramic crown systems. AB - The coefficient of thermal expansion of core and veneer porcelains for all ceramic crowns must be compatible to prevent formation of stresses during the firing cycles. The purpose of this study was to use a thermal shock test to evaluate the crazing resistance of six all-ceramic crown systems. The systems tested were: Vita In-Ceram, Vita Hi-Ceram, Dicor veneered with Vitadur N, magnesia core veneered with Ceramco II, magnesia core veneered with Silhouette, and magnesia core veneered with Vita VMK 68. A maxillary central incisor was prepared with 1.0 mm axial and 1.5 mm incisal reduction. Refractory dies were prepared and crowns were fabricated using the manufacturers' recommendations. Six specimens of each system were placed inside a beaker in a furnace at 90 degrees C. After 15 min heat soak, ice water was poured into the beaker through a funnel. The samples were dried in air, reheated, and inspected for crazing using light microscopy. If crazing was observed, this would constitute a failure at a temperature difference (delta T) of 90 degrees C. If no failure occurred, the test was repeated at increasing temperature increments of 10 degrees C until failure. The crazing resistance of each system, expressed as the mean delta T, was: > 200 (Hi-Ceram), 163 +/- 14 (In-Ceram), 152 +/- 19 (Dicor/Vitadur N), 143 +/- 5 (magnesia core/Vita VMK 68), 122 +/- 21 (magnesia core/Silhouette), and 118 +/- 10 (magnesia core/Ceramco II) degrees C. All systems tested resisted crazing due to quenching in ice cold water from 100 degrees C. Systems with lower coefficients of expansion showed significantly greater resistance to thermal shock using ANOVA. PMID- 8207031 TI - Effect of pretreating porous webs on stromal fibroplasia in vivo. AB - We have previously demonstrated that keratocytes penetrate and deposit collagen after a porous web is inserted into interlamellar corneal pockets. In these studies our goal was to determine whether pretreatment of the porous discs would enhance wound healing. We have evaluated four methods of pretreating the porous disc prior to its placement in the stroma. The pretreated discs were followed in vivo for a period of 42 days. The criteria we used to determine whether pretreatment affected wound healing were: collagen deposition, extent of fibroplasia, the synthetic rate of keratocytes within the disc, and lack of edema. Our results indicate that preseeding with stromal keratocytes enhanced the overall synthetic rate and specifically enhanced the amount of collage deposited within the web. PMID- 8207032 TI - Microvascular endothelial cell sodding of ePTFE vascular grafts: improved patency and stability of the cellular lining. AB - Small diameter (< 6 mm) synthetic vascular grafts fail at a clinically unacceptable rate due in large part to their inherent thrombogenicity. The development of a new cellular lining on synthetic vascular grafts would most likely improve the patency rates observed for these grafts in small diameter positions. We have evaluated the use of endothelial cell transplantation to accelerate the formation of a cell lining using microvascular endothelial cells derived from canine falciform ligament fat. This source of fat is histologically similar to human liposuction fat and was isolated using a collagenase digestion technique identical to methods used for human liposuction fat microvessel endothelial cell isolation. The isolated fat endothelial cells were sodded onto 4 mm ePTFE grafts using pressure to force the cells onto the luminal surface. This pressure sodding method permitted cell deposition in less then 3 min. Sodded and control (non-cell-treated) grafts were implanted as interpositional paired grafts using end-to-end anastomoses in the carotid arteries of mixed breed dogs. Each dog therefore received a sodded graft on one side and a control graft on the contralateral side. After 12 weeks of implantation all control grafts were occluded while 86% of the cell-sodded grafts remained patent. Statistical evaluation of the data revealed a significant improvement in patency of cell sodded grafts (McNemar's chi 2 P = .02). Morphological evaluation of grafts explanted at 5, 12, 26, and 52 weeks following implantation revealed the presence of a cell lining on sodded grafts which remained stable for a period of at least one year. This new cell lining exhibited morphologic characteristics of a nonthrombogenic endothelial cell lining. The development of this new intima, evaluated 5 weeks-1 year after implantation, was not associated with a progressive intimal hyperplasia. From these data we conclude that microvessel endothelial cells derived from canine falciform ligament fat can be rapidly isolated using an operating room compatible method. Cell deposition on synthetic grafts is subsequently accelerated using a pressure sodding technique. A cellular lining forms on the inner surface and is associated with a statistically significant improvement in the function of sodded grafts in a canine carotid artery model. PMID- 8207033 TI - Confocal laser scanning microscopy (CLSM) for the study of collagen sponge microstructure. AB - This study uses confocal laser scanning microscopy (CLSM) to assess the microstructure of collagen sponges providing an accurate quantification of porosity under conditions similar to those experienced by cells growing on the sponges during culture. CLSM offers several advantages over scanning electron microscopy (SEM) and conventional optical microscopy for this kind of study, the most important of which is probably the absence of artifacts associated with the extensive preparation of samples required for the latter two methods. When the "pan-side" surface of collagen sponges was studied, it was found that the pore sizes increased with increasing depth into the sponge. Collagen sponges frozen in a -70 degrees C freezer had a more open structure than ones frozen on the stage of a tissue dryer. These different pore sizes are thought to reflect different freezing rates in the samples. PMID- 8207034 TI - Blood compatibility of sputter-deposited alumina films. AB - The surface modification of metals by the application of blood compatible ceramics is one approach to developing durable and blood-compatible materials. The blood compatibility of sputter-deposited alumina films was investigated in vitro. The alumina films were prepared by reactive sputtering and conventional sputtering. Diffractometer studies of the alumina films indicate that the sputter deposited alumina films have amorphous structures. Electron spectroscopy chemical analysis studies of the alumina films indicate that the sputter-deposited alumina films are nonstoichiometric (O/A1 ratio of 1.15-1.66). We examined the platelet reaction to the alumina films and the intrinsic coagulation factor XII activation by the alumina films. Medical grade segmented polyurethane was also tested. The alumina films experienced an adhesion of about 50% fewer platelets than the segmented polyurethane. Also, fewer platelet morphologic changes were observed on the alumina films than on the segmented polyurethane. Factor XII activation was less on the alumina films than on the segmented polyurethane. Surface modification by the sputter-deposited alumina films is promising for developing blood-compatible and durable materials. PMID- 8207035 TI - Hemocompatibility on graft copolymers composed of poly(2-methacryloyloxyethyl phosphorylcholine) side chain and poly(n-butyl methacrylate) backbone. AB - To improve the hemocompatibility on hydrophobic biomedical materials by a simple coating technique, graft copolymers composed of a hydrophilic side chain with phospholipid polar groups and a hydrophobic backbone were synthesized. The hydrophilic chain had phospholipid polar groups, poly[2-methacryloyloxyethyl phosphorylcholine (MPC)], and the hydrophobic backbone was poly[n-butyl methacrylate (BMA)]. Because the graft copolymers obtained could dissolve in ethanol, they could be used as a coating material. When the poly(MPC-graft-BMA) was coated onto a poly(BMA) membrane, the composition of the MPC units on the surface was maintained in the bulk graft copolymer even after immersion in water. Protein adsorption on the membrane coated with the graft copolymer from human plasma detected by a gold-colloid labeled immunoassay was drastically decreased compared with that on glass and the original membrane. Moreover, blood cell adhesion, activation, and aggregation on the membrane after contact with human citrated whole blood were suppressed by the coating of the graft copolymer. These results clearly show that the poly(MPC-graft-BMA) is a suitable material for improving hemocompatibility on the biomedical devices because of its protein adsorption and cell adhesion resistant properties. PMID- 8207036 TI - Comparison of 316LVM and MP35N alloys as charge injection electrodes. AB - An In vitro comparison of the corrosion response of 316LVM stainless steel and MP35N (a CoNiCrMo alloy) electrodes under conditions appropriate to applications in functional electrical stimulation (FES) was made. Electrodes of both alloys were subjected to a cathodic 40 microC/cm2 charge injection protocol and the potential transient response was recorded over a 96 h period. The transient responses were compared with potentiodynamic polarization data used to establish the quasiequilibrium response of the alloys in the carbonate and phosphate buffered saline electrolyte used in the study. The MP35N electrodes exhibited extensive pitting corrosion during charge injection, whereas little corrosion was observed on 316LVM electrodes. An explanation for the susceptibility of MP35N to corrosion during charge injection is found in the potentiodynamic polarization data, which reveal a breakdown potential (critical pitting potential) of 0.45 V (SCE) for MP35N compared with 1.05 V (SCE) for 316LVM. Factors that may influence corrosion response during charge injection from alloys exhibiting active-passive behavior are discussed. PMID- 8207038 TI - Adsorption and activation of zymogens at solid-liquid interfaces. I. Chymotrypsinogen on alkylamino modified silica derivatives. AB - Silica beads were modified with alkylamino groups of different lengths (C2, C4, C6, C8, and C10) and hydrophobicity. The relationship between surface structure and adsorption of chymotrypsinogen followed by its activation with trypsin at the solid-liquid interface was studied. From the adsorption isotherms, it follows that underivatized silica adsorbed chymotrypsinogen (CTG) well. The adsorption of CTG on alkylamino modified silicas appeared to correlate with the hydrophobicity of the latter. The longer the alkyl chains were, the higher was the amount of adsorbed CTG. The activation of adsorbed CTG with trypsin at the solid-liquid interface was a slower process when compared with the activation conducted in solution. Parallel experiments were performed with chymotrypsin (CT). The adsorption behavior was similar to that of CTG. The activity of adsorbed CT was inversely proportional to the hydrophobicity of the beads. These results correlated well with the desorption of CT after repeated washings. Repeated addition of substrate (Gly-Gly-Phe-NAp) to the CT covered beads resulted in the CT desorption. The higher the hydrophobicity of the beads was, the lower was the desorption of CT. PMID- 8207037 TI - Cellular uptake of titanium and vanadium from addition of salts or fretting corrosion in vitro. AB - The use of titanium and titanium-6% aluminum-4% vanadium alloy for dental and orthopedic implants has increased in the last decade. The implants are presumed to be compatible because osseointegration, bony apposition, and cell attachment are known. However, the cellular association of titanium and vanadium have remained unknown. This study examined the uptake of salts or fretting corrosion products. Titanium was not observed to be toxic to the cells. Vanadium was toxic at levels greater than 10 micrograms/mL. The percentage of cellular association of titanium was shown to be about 10 times that of vanadium. The percentage of cellular association of either element was greater from fretting corrosion than from the addition of salts. The presence of vanadium did not affect the cellular uptake of titanium. The presence of titanium decreased the cell association of vanadium. PMID- 8207039 TI - Subcutaneous, catheter-related inflammation in a rabbit model correlates with peripheral vein phlebitis in human volunteers. AB - In the development of a polyurethane vascular catheter with anti-infective properties, it became desirable to develop a measure of tissue inflammation. This was investigated in a rabbit model by implanting uncoated catheters and catheters coated with heparin (HEP), chlorhexidine (CH), or CH/HEP in the subcutaneous space with or without 10(4) Staphylococcus aureus. At intervals of 2, 4, and 7 days after implantation, animals were sacrificed; tissue blocks containing catheters were removed and preserved with formaldehyde; and sections were stained with hematoxylin and eosin. Using a histologic index, 240 sections (10 for each experimental condition) were evaluated by two investigators blinded to experimental conditions. Uncoated catheters or catheters coated with CH alone had a lower histologic index (less inflammation) than catheters coated with HEP alone or CH/HEP (P < .05). When catheters were inoculated with S. aureus, those coated with CH, with or without HEP, had a lower histologic index than uncoated catheters (P < .05). Next, 30 volunteers had a control catheter inserted in a vein in one forearm and a catheter coated with either CH alone or CH/HEP in a vein in the other forearm. After 96 h of observation there was a greater risk of phlebitis associated with CH/HEP catheters than control catheters (P < .05), and no difference in the risk of phlebitis between CH catheters and control catheters (P = 0.43). Thus, the amount of inflammation around the catheter in the subcutaneous space of rabbit correlated with the risk of peripheral vein phlebitis. PMID- 8207040 TI - Interfacial behavior of PEO/PBT copolymers (Polyactive) in a calvarial system: an in vitro study. AB - Polyactive, a polyethylene oxide/polybutylene terephthalate (PEO/PBT) copolymer, has been reported to display bone-bonding behavior. Although a detailed description of the in vivo bone/Polyactive interface is available, the underlying bone-bonding mechanism is still largely unknown. In this in vitro study, a calvarial envelope method has been adopted to reproduce the in vivo bone-bonding phenomenon and subsequently to obtain information on the biological effect of varying PEO/PBT segment ratios. The following PEO/PBT ratios were examined: 70/30, 60/40, 55/45, 40/60, and 30/70. Light microscopy (LM) and scanning (SEM), transmission (TEM), and backscatter electron microscopy (BSE), as well as X-ray microanalysis (XRMA), were employed. Within the period of analysis (3 weeks), an intimate contact between mineralized deposition and the 70/30, 60/40, and, to a lesser extent, the 55/45 surface was observed. Calcified areas developed within the surface of these PEO/BPT proportions during the culture period. Needle-shaped crystals from the mineralized tissue compartment and from calcified areas within the materials surface were intermingled at the interface, providing a morphologic continuity. A cellular layer was interposed with the mineralization front and the noncalcified 40/60 and 30/70 substrates. Apparently, the percentage of PEO is important for calcification within the near surface of the polymer. This relation is such that the higher the PEO content in PEO/PBT ratios, the more rapid the calcification. The occurrence of material calcification is considered to be largely responsible for the subsequent interfacial interactions. The calvarial envelope culture method allows not only reproduction of the in vivo bone/Polyactive interface, but also a relatively rapid differentiation within the range of PEO/PBT ratios.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207041 TI - Cancer survival and the mind. PMID- 8207042 TI - Aberrant expression, function and localization of connexins in human esophageal carcinoma cell lines with different degrees of tumorigenicity. AB - We have analyzed the level of mRNA expression and protein localization of the gap junction protein connexins (Cx) 26, 32, and 43, as well as gap-junctional intercellular communication (GJIC) in seven human esophageal carcinoma cell lines (TE series). These cell lines exhibited various degrees of tumorigenicity in nude mice; two (TE-1 and TE-8) formed progressively growing tumors, four (TE-2, TE-3, TE-9, and TE-13) developed non-progressing tumors and one (TE-10) showed no tumorigenicity. We found that normal human esophageal tissue expressed both Cx26 and Cx43 and that most of the cell lines expressed lower amounts of Cx26 and Cx43 mRNAs than normal human esophageal tissues or none at all. The co-expression of Cx26 and Cx43 mRNAs and proteins was observed only in two cell lines (TE-3 and TE 9) that showed a high level of GJIC and non-progressive tumor development. However, the non-tumorigenic cell line TE-10 did not express either connexin. A possible regulator of GJIC, E-cadherin, was expressed in all cell lines. These results suggest that aberrant expression and function of connexins are common among human esophageal carcinoma cell lines, but there is no quantitative relationship between connexin expression and tumorigenic properties of these cell lines. PMID- 8207044 TI - Effect of salt on cell proliferation and N-methyl-N'-nitro-N-nitrosoguanidine penetration to proliferative cells in the forestomach of rats. AB - We have studied the effect of intragastric instillation of 4.5 M NaCl on cell proliferation and carcinogen penetration into the forestomach of Wistar rats at different time intervals after salt exposure. Cells in the S-phase were labelled by incorporation of bromodeoxyuridine and located after immunohistochemistry. N [3H]Methyl-N'-nitro-N-nitrosoguanidine ([3H]MNNG) was used as the carcinogen and penetration of [3H]MNNG to proliferative cells was determined by autoradiography. The number of cells in S-phase per millimetre epithelium length 12 h and 24 h after salt exposure (32.2 +/- 11.9 and 20.6 +/- 7.4) was significantly higher than in the control animals (9.4 +/- 3.6). No increase in cell proliferation occurred during the first 2 h after salt exposure. Microscopy also revealed oedema in the lamina propia. The forestomach blood flow was not influenced by the application of hypertonic saline. [3H]MNNG at a concentration of 40 micrograms/ml did not penetrate to the proliferative cells in the forestomach and no effect of salt pretreatment on carcinogen penetration was seen. The low penetration of [3H]MNNG to proliferative cells in the forestomach epithelium may explain why this concentration of MNNG given in drinking water over several weeks usually does not induce squamous cell carcinomas in the forestomach. The previously observed cocarcinogenic effect of salt on squamous cell cercinogenesis in the upper gastrointestinal tract could be due to the observed increase in cell proliferation after salt exposure. PMID- 8207043 TI - Expression of mitochondrial genes and DNA-repair-related nuclear genes is altered in xeroderma pigmentosum fibroblasts. AB - Differential hybridization was used to detect repair defects in xeroderma pigmentosum (XP) that are not amenable to current analyses. cDNA libraries were constructed from cytoplasmic RNA of normal and XP fibroblast strains (complementation groups A and D) and analyzed for differential gene expression. More than 40,000 lambda gt10 cDNA clones were differentially screened with in vitro transcripts made from cDNA in the pBluescript vector. Six differential clones were detected in the libraries of the XP group A and D strains which caused stronger or weaker signals when probed with transcripts from XP strains than with those from the normal strains. Two clones coded for mitochondrial genes: mitochondrial 16 S rRNA and ATPase 6L. Overexpression of mitochondrial genes in XP may indicate that functions of the ATP-generating system are impaired since such functions are intensified whenever they become insufficient, for example as a consequence of DNA damage. It is tempting to assume that abnormal mitochondria are one of the causes for the neurological malfunctions in XP. Furthermore, densitometric analysis of Northern blots revealed that mRNA of lactate dehydrogenase, chain M, was less abundant in four XP group A strains (extent of reduction: 70%) and in two XP group D strains (extent of reduction: 58%). Enzyme activity was also diminished. In addition, mRNA of the gene for glyceraldehyde-3-phosphate dehydrogenase was less expressed in the same XP group A and D fibroblast strains investigated (reduction in both complementation groups: 50%). Both glycolytic enzymes have nuclear functions apart from their role in sugar metabolism. Lactate dehydrogenase, chain M, is identical to a helix destabilizing protein; it is closely associated with chromatin and unfolded DNA, suggesting a role in DNA synthesis and transcription. The 37-kDa subunit of glyceraldehyde-3-phosphate dehydrogenase is involved in transcription and was shown to be identical to uracil-DNA glycosylase, a base-excision repair enzyme. We presume that the nuclear functions of these glycolytic enzymes may be thwarted in the XP strains investigated and may account for malfunctions in XP, particularly for neurological disturbances. PMID- 8207045 TI - Influence of cytokines on mdr1 expression in human colon carcinoma cell lines: increased cytotoxicity of MDR relevant drugs. AB - We investigated the effects of tumor necrosis factor (TNF) alpha, interferon (IFN) gamma and interleukin-2 (IL-2) on the mdr1 gene expression in four human colon carcinoma cell lines (Lo Vo, HT 115, SW 480, and LS 174T) at different times (8, 24, 48, and 72 h). We found no significant changes in mdr1 expression after 8 h and 24 h of cytokine treatment in all four lines. After 48 h and 72 h, however, a marked reduction of mdr1 expression in Lo Vo, HT 115, and SW 480 cells and an unaffected expression in LS 174T cells was observed. We examined whether the cytokine-mediated reduction of mdr1 expression correlates to the multidrug resistance (MDR) phenotype. In those cell lines showing a decreased mdr1 expression after a long-term cytokine pretreatment we found a dramatic enhancement of cytotoxicity of the MDR relevant drugs vincristine and doxorubicin, whereas LS 174T cells remained resistant. By contrast, the simultaneous application of cytokines and cytostatics caused no additive or synergistic effects. We conclude that in certain colon carcinoma cell lines a decreased mdr1 expression caused by prolonged cytokine pretreatment correlates with an enhanced cytotoxicity of drugs susceptible to MDR as an MDR-overcoming effect. PMID- 8207046 TI - Effects of group B Streptococcus toxin on long-term survival of mice bearing transplanted Madison lung tumors. AB - GBS toxin is a polysaccharide exotoxin produced by group B Streptococcus. This organism causes sepsis and respiratory distress in human neonates (so-called early onset disease). This disease is marked by a strong inflammatory response only in the lung, with pulmonary sequestration of granulocytes and extensive capillary endothelial damage, and occurs only during the first few days after birth. We have found that a similar inflammatory response can be induced by i.v. infusion of picomole quantities of GBS toxin in the developing vasculature of transplanted tumors in mice and can significantly retard the tumor growth. When optimum treatment with GBS toxin was started shortly after tumor implantation, a majority of tumors in the mice regressed and the mice remained tumor-free for over 5 months. Some tumors regressed in mice receiving short-term treatment with GBS toxin, but recurred after the treatment was stopped. Median survival times were extended by all regimens and all doses of GBS toxin tested. No evidence of toxicity to the vasculature of other tissues was observed. GBS toxin is being tested for cancer therapy in humans. PMID- 8207047 TI - Skin-tumour-promoting activity of processed bidi tobacco in hairless S/RV Cri-ba mice. AB - Workers engaged in processing tobacco for the manufacture of bidis, the most popular smoking devices in India, are exposed to tobacco dust, volatile components and flakes via nasopharyngeal and cutaneous routes. In order to evaluate the risk of occupational tobacco exposure, the complete carcinogenic action of an aqueous extract of bidi tobacco (ATE), its ability to initiate and promote skin papillomas and to convert these to carcinomas, was tested in hairless S/RV Cri-ba mice using the skin tumorigenesis protocol. Epidermal cell kinetics and tissue alterations were recorded after a single or multiple applications of ATE to 7,12-dimethylbenz[a]-anthracene(DMBA)- initiated mouse skin. While ATE did not exhibit complete carcinogenic, initiating or progressor activity, it effectively promoted skin papilloma formation in DMBA-initiated mice. An increase in papilloma yield per mouse above the control was noted only after 30 weeks of promotion, and at week 40 of promotion with 5 mg and 50 mg ATE it was significantly higher than that in the control mice (9.69 +/- 1.30 and 11.73 +/- 1.38 compared to 4.70 +/- 1.01; P < 0.01). Mild epidermal hyperplasia, increase in mitotic activity and dermal thickness induced by a single application of ATE persisted upon multiple treatment and correlated well with its tumour promoting activity. The findings indicate that occupational exposure to bidi tobacco may pose a cancer risk among workers in the bidi industry. PMID- 8207048 TI - Multicentric extraabdominal desmoid tumour: a case report. AB - The very rare condition of multicentric desmoid tumours involving two distant and apparently independent sites is reported in a 17-year-old man. The tumours grew simultaneously and reached approximately equal size. No evidence of familiar polyposis or any other feature of Gardner's syndrome were noted. The proximal desmoid tumour developed from the left hip region and extended into the femoral bone, whereas the distal mass was attached to the left popliteal fossa infiltrating the flexor muscles, the nerves and vessels. On the basis of the good results published recently in the literature and our own earlier experiences, the intralesional resection of the desmoid tumours was completed with postoperative fractionated radiotherapy. PMID- 8207049 TI - Tumour-associated trypsin inhibitor in the diagnosis of pancreatic carcinoma. AB - The serum values of tumour-associated trypsin inhibitor (TATI) were measured in a prospective series of 97 patients with jaundice, 36 patients with unjaundiced cholestasis and 21 patients with suspicion of chronic pancreatitis or a pancreatic tumour, to assess its value in diagnosing pancreatic cancer. There were altogether 15 patients with cancer of the pancreas and 2 patients with cancer of the papilla of Vater. The highest serum TATI values were noticed in patients with choledocholithiasis, and raised values were also seen in patients with malignant disease of the liver or bile ducts. In the patients with pancreatic cancer, chronic pancreatitis or benign liver disease, the serum TATI values showed lower levels. The sensitivity of TATI in diagnosing pancreatic cancer was 41.1% with a specificity of 63.5% and an efficiency of 61.0%. In comparison to carcinoembryonic antigen (CEA), carbohydrate antigens CA 50, CA 242, tissue polypeptide antigen and tissue polypeptide-specific antigen, TATI showed a lower diagnostic value. When TATI was analysed in combination with the other markers (two tests positive), the combination of CEA with TATI reached the highest specificity (95.6%), efficiency (89.6%) and positive likelihood ratio (9.3). The results suggest that the diagnostic value of TATI is inferior to that of the established markers, but because of its different nature, it may be of help when used in combination as a complementary serum tumour marker in the diagnosis of pancreatic cancer. PMID- 8207050 TI - Conference on carcinogenic risk factors in the occupational environment (Krebserzeugende Gefahrstoffe in der Arbeitsumwelt). Frankfurt/Main, October 1993. AB - In this summary, J. Konietzko (Mainz) stressed the exceptional position of occupational cancer, which is due to the long latent period between exposure to specific carcinogens and cancer manifestation. Obviously, this long latent period of years to decades poses problems in the search for the etiology of occupational cancer. Three methodological areas are instrumental in overcoming these problems. They include epidemiological investigations, in vitro experiments and animal experiments, which have to complement each other. A highly important area within the aetiological research is the field of syncarcinogenesis. Up to now, some research on combined effects has been done, but this field urgently needs further efforts and promotion since the threat of more than additive carcinogenic effects can be ruled out or prevented only after the necessary knowledge has been gathered from properly conducted basic research. Within the discussion of occupational cancer, three areas have to be discriminated; they relate to cancer as an occupational disease, as a problem within the insurance laws, and as a risk that requires preventive measures. Its acknowledgement as an occupational disease is based on strict legal preconditions that limit any generosity. Such a procedure is too reserved, however, as far as preventive measures are concerned. In this area, more generous criteria are required, which do not only result from scientific procedures. Prevention is subject to a clear ranking; primary prevention, i.e. the elimination of carcinogens from the workplace, has priority. If the elimination of occupational hazards is impossible, a quantitative risk assessment that takes account of synergistic carcinogenic effects can help to set priorities. The impossibility of a complete primary prevention necessitates secondary and tertiary prevention, which correspond to early diagnosis and follow up management of occupational cancer. Each of these areas needs continued attention. PMID- 8207051 TI - Antitumour activity of coumarin and 7-hydroxycoumarin against 7,12 dimethylbenz[a]anthracene-induced rat mammary carcinomas. AB - Female SD rats with established 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumours were treated with coumarin (20 mg/kg body weight; six times per week) or its metabolite 7-hydroxycoumarin (20 mg/kg) for 4 weeks. The anti oestrogen tamoxifen (8.8 mg/kg) served as the reference drug. The inhibitory effect of coumarin was similar to that of tamoxifen [mean change of tumour area: 428% (coumarin) compared to 528% (tamoxifen); control 822%]. The strongest inhibition was observed with 7-hydroxycoumarin (248%); the difference compared to the control was significant (P < 0.01). Neither coumarin nor 7-hydroxycoumarin reduced the number of tumours appearing during treatment as tamoxifen did. However, the size of the tumours treated with coumarin or its metabolite was generally much smaller than those in the tamoxifen group or in the control group. From the data obtained it appears that coumarin and 7-hydroxycoumarin inhibit the growth of tumours that have reached a certain size but do not prevent the formation of tumours after exposure to the carcinogen. PMID- 8207052 TI - Hyaluronidase as an antidote to extravasation of Vinca alkaloids: clinical results. AB - Skin necrosis is a recognized potential consequence of an inadvertent extravasation of Vinca alkaloids in the surrounding tissues during i.v. administration. Experimental studies suggest that hyaluronidase, an enzyme that degrades hyaluronic acid and improves the absorption of locally injected drugs, can reduce the risk of progressing to skin necrosis. On this basis, we used this enzyme as a local treatment after extravasations of Vinca alkaloids in seven patients. No patient suffered from subsequent skin necrosis. To the best of our knowledge, this is the first clinical report confirming the positive findings of experimental studies on the effectiveness of this antidote. PMID- 8207053 TI - Homologous pairing is reduced but not abolished in asynaptic mutants of yeast. AB - In situ hybridization was used to examine chromosome behavior at meiotic prophase in the rad50S, hop1, rad50, and spo11 mutants of Saccharomyces cerevisiae, which are defective in chromosome synapsis and meiotic recombination. Painting of chromosomes I and III revealed that chromosome condensation and pairing are reduced in these mutants. However, there is some residual pairing in meiosis, suggesting that homologue recognition is independent of synaptonemal complex formation and recombination. Association of homologues was observed in the rad50, rad50S, and spo11 mutants, which are defective in the formation or processing of meiotic double-strand breaks. This indicates that double-strand breaks are not an essential component of the meiotic homology searching mechanism or that there exist additional or alternative mechanisms for locating homologues. PMID- 8207054 TI - Disruptions in Golgi structure and membrane traffic in a conditional lethal mammalian cell mutant are corrected by epsilon-COP. AB - The CHO cell temperature-sensitive mutant ldlF exhibits two defects in membrane traffic at the nonpermissive temperature (39.5 degrees C): rapid degradation of LDL receptors, possibly caused by endocytic missorting, and disruption of ER through-Golgi transport. Here, we show that at 39.5 degrees C, the Golgi in ldlF cells dissociated into vesicles and tubules. This dissociation was inhibited by AlF4-, suggesting trimeric G proteins are involved in the dissociation mechanism. This resembled the effects of brefeldin A on wild-type cells. We isolated a hamster cDNA that specifically corrected the ts defects of ldlF cells, but not those of other similar ts mutants (ldlE, ldlG, ldlH, and End4). Its predicted protein sequence is conserved in humans, rice, Arabidopsis, and Caenorhabditis elegans, and is virtually identical to that of bovine epsilon-COP, a component of the coatomer complex implicated in membrane transport. This provides the first genetic evidence that coatomers in animal cells can play a role both in maintaining Golgi structure and in mediating ER-through-Golgi transport, and can influence normal endocytic recycling of LDL receptors. Thus, along with biochemical and yeast genetics methods, mammalian somatic cell mutants can provide powerful tools for the elucidation of the mechanisms underlying intracellular membrane traffic. PMID- 8207055 TI - Transport and intracellular distribution of MHC class II molecules and associated invariant chain in normal and antigen-processing mutant cell lines. AB - We have compared the intracellular transport and subcellular distribution of MHC class II-invariant chain complexes in a wild-type HLA-DR3 homozygous cell line and a mutant cell line, T2.DR3. The latter has a defect in antigen processing and accumulates HLA-DR3 molecules associated with an invariant chain-derived peptide (CLIP) rather than the normal complement of peptides derived from endocytosed proteins. We find that in the wild-type cells, CLIP is transiently associated with HLA-DR3 molecules, suggesting that the peptide is a normal class II associated intermediate generated during proteolysis of the invariant chain. In the mutant cell line proteolysis of the invariant chain is less efficient, and HLA-DR3/CLIP complexes are generated much more slowly. Examination of the mutant cell line by immunoelectronmicroscopy shows that class II-invariant chain complexes accumulate intracellularly in large acidic vesicles which contain lysosomal markers, including beta-hexosaminidase, cathepsin D, and the lysosomal membrane protein CD63. The markers in these vesicles are identical to those seen in the class II-containing vesicles (MIICs) seen in the wild-type cells but the morphology is drastically different. The vesicles in the mutant cells are endocytic, as measured by the internalization of BSA-gold conjugates. The implication of these findings for antigen processing in general and the nature of the mutation in particular are discussed. PMID- 8207056 TI - Compartmentalized structure of the plasma membrane for receptor movements as revealed by a nanometer-level motion analysis. AB - Movements of transferrin and alpha 2-macroglobulin receptor molecules in the plasma membrane of cultured normal rat kidney (NRK) fibroblastic cells were investigated by video-enhanced contrast optical microscopy with 1.8 nm spatial precision and 33 ms temporal resolution by labeling the receptors with the ligand coated nanometer-sized colloidal gold particles. For both receptor species, most of the movement trajectories are of the confined diffusion type, within domains of approximately 0.25 microns2 (500-700 nm in diagonal length). Movement within the domains is random with a diffusion coefficient approximately 10(-9) cm2/s, which is consistent with that expected for free Brownian diffusion of proteins in the plasma membrane. The receptor molecules move from one domain to one of the adjacent domains at an average frequency of 0.034 s-1 (the residence time within a domain approximately 29 s), indicating that the plasma membrane is compartmentalized for diffusion of membrane receptors and that long-range diffusion is the result of successive intercompartmental jumps. The macroscopic diffusion coefficients for these two receptor molecules calculated on the basis of the compartment size and the intercompartmental jump rate are approximately 2.4 x 10(-11) cm2/s, which is consistent with those determined by averaging the long-term movements of many particles. Partial destruction of the cytoskeleton decreased the confined diffusion mode, increased the simple diffusion mode, and induced the directed diffusion (transport) mode. These results suggest that the boundaries between compartments are made of dynamically fluctuating membrane skeletons (membrane-skeleton fence model). PMID- 8207057 TI - Primary mouse myoblast purification, characterization, and transplantation for cell-mediated gene therapy. AB - The transplantation of cultured myoblasts into mature skeletal muscle is the basis for a new therapeutic approach to muscle and non-muscle diseases: myoblast mediated gene therapy. The success of myoblast transplantation for correction of intrinsic muscle defects depends on the fusion of implanted cells with host myofibers. Previous studies in mice have been problematic because they have involved transplantation of established myogenic cell lines or primary muscle cultures. Both of these cell populations have disadvantages: myogenic cell lines are tumorigenic, and primary cultures contain a substantial percentage of non myogenic cells which will not fuse to host fibers. Furthermore, for both cell populations, immune suppression of the host has been necessary for long-term retention of transplanted cells. To overcome these difficulties, we developed novel culture conditions that permit the purification of mouse myoblasts from primary cultures. Both enriched and clonal populations of primary myoblasts were characterized in assays of cell proliferation and differentiation. Primary myoblasts were dependent on added bFGF for growth and retained the ability to differentiate even after 30 population doublings. The fate of the pure myoblast populations after transplantation was monitored by labeling the cells with the marker enzyme beta-galactosidase (beta-gal) using retroviral mediated gene transfer. Within five days of transplantation into muscle of mature mice, primary myoblasts had fused with host muscle cells to form hybrid myofibers. To examine the immunobiology of primary myoblasts, we compared transplanted cells in syngeneic and allogeneic hosts. Even without immune suppression, the hybrid fibers persisted with continued beta-gal expression up to six months after myoblast transplantation in syngeneic hosts. In allogeneic hosts, the implanted cells were completely eliminated within three weeks. To assess tumorigenicity, primary myoblasts and myoblasts from the C2 myogenic cell line were transplanted into immunodeficient mice. Only C2 myoblasts formed tumors. The ease of isolation, growth, and transfection of primary mouse myoblasts under the conditions described here expand the opportunities to study muscle cell growth and differentiation using myoblasts from normal as well as mutant strains of mice. The properties of these cells after transplantation--the stability of resulting hybrid myofibers without immune suppression, the persistence of transgene expression, and the lack of tumorigenicity--suggest that studies of cell-mediated gene therapy using primary myoblasts can now be broadly applied to mouse models of human muscle and non-muscle diseases. PMID- 8207058 TI - The Schizosaccharomyces pombe cdc3+ gene encodes a profilin essential for cytokinesis. AB - The fission yeast Schizosaccharomyces pombe divides by medial fission and, like many higher eukaryotic cells, requires the function of an F-actin contractile ring for cytokinesis. In S. pombe, a class of cdc- mutants defective for cytokinesis, but not for DNA replication, mitosis, or septum synthesis, have been identified. In this paper, we present the characterization of one of these mutants, cdc3-124. Temperature shift experiments reveal that mutants in cdc3 are incapable of forming an F-actin contractile ring. We have molecularly cloned cdc3 and used the cdc3+ genomic DNA to create a strain carrying a cdc3 null mutation by homologous recombination in vivo. Cells bearing a cdc3-null allele are inviable. They arrest the cell cycle at cytokinesis without forming a contractile ring. DNA sequence analysis of the cdc3+ gene reveals that it encodes profilin, an actin-monomer-binding protein. In light of recent studies with profilins, we propose that Cdc3-profilin plays an essential role in cytokinesis by catalyzing the formation of the F-actin contractile ring. Consistent with this proposal are our observations that Cdc3-profilin localizes to the medial region of the cell where the F-actin contractile ring forms, and that it is essential for F-actin ring formation. Cells overproducing Cdc3-profilin become elongated, dumbbell shaped, and arrest at cytokinesis without any detectable F-actin staining. This effect of Cdc3-profilin overproduction is relieved by introduction of a multicopy plasmid carrying the actin encoding gene, act1+. We attribute these effects to potential sequestration of actin monomers by profilin, when present in excess. PMID- 8207059 TI - Cyclin-like accumulation and loss of the putative kinetochore motor CENP-E results from coupling continuous synthesis with specific degradation at the end of mitosis. AB - CENP-E is a kinesin-like protein that binds to kinetochores through the early stages of mitosis, but after initiation of anaphase, it relocalizes to the overlapping microtubules in the midzone, ultimately concentration in the developing midbody. By immunoblotting of cells separated at various positions in the cell cycle using centrifugal elutriation, we show that CENP-E levels increase progressively across the cycle peaking at approximately 22,000 molecules/cell early in mitosis, followed by an abrupt (> 10 fold) loss at the end of mitosis. Pulse-labeling with [35S]methionine reveals that beyond a twofold increase in synthesis between G1 and G2, interphase accumulation results primarily from stabilization of CENP-E during S and G2. Despite localizing in the midbody during normal cell division, CENP-E loss at the end of mitosis is independent of cytokinesis, since complete blockage of division with cytochalasin has no affect on CENP-E loss at the M/G1 transition. Thus, like mitotic cyclins, CENP-E accumulation peaks before cell division, and it is specifically degraded at the end of mitosis. However, CENP-E degradation kinetically follows proteolysis of cyclin B in anaphase. Combined with cyclin A destruction before the end of metaphase, degradation of as yet unidentified components at the metaphase/anaphase transition, and cyclin B degradation at or after the anaphase transition, CENP-E destruction defines a fourth point in a mitotic cascade of timed proteolysis. PMID- 8207061 TI - Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. AB - Calcium-dependent cell-cell adhesion is mediated by the cadherin family of cell adhesion proteins. Transduction of cadherin adhesion into cellular reorganization is regulated by cytosolic proteins, termed alpha-, beta-, and gamma-catenin (plakoglobin), that bind to the cytoplasmic domain of cadherins and link them to the cytoskeleton. Previous studies of cadherin/catenin complex assembly and organization relied on the coimmunoprecipitation of the complex with cadherin antibodies, and were limited to the analysis of the Triton X-100 (TX-100)-soluble fraction of these proteins. These studies concluded that only one complex exists which contains cadherin and all of the catenins. We raised antibodies specific for each catenin to analyze each protein independent of its association with E cadherin. Extracts of Madin-Darby canine kidney epithelial cells were sequentially immunoprecipitated and immunoblotted with each antibody, and the results showed that there were complexes of E-cadherin/alpha-catenin, and either beta-catenin or plakoglobin in the TX-100-soluble fraction. We analyzed the assembly of cadherin/catenin complexes in the TX-100-soluble fraction by [35S]methionine pulse-chase labeling, followed by sucrose density gradient fractionation of proteins. Immediately after synthesis, E-cadherin, beta-catenin, and plakoglobin cosedimented as complexes. alpha-Catenin was not associated with these complexes after synthesis, but a subpopulation of alpha-catenin joined the complex at a time coincident with the arrival of E-cadherin at the plasma membrane. The arrival of E-cadherin at the plasma membrane coincided with an increase in its insolubility in TX-100, but extraction of this insoluble pool with 1% SDS disrupted the cadherin/catenin complex. Therefore, to examine protein complex assembly in both the TX-100-soluble and -insoluble fractions, we used [35S]methionine labeling followed by chemical cross-linking before cell extraction. Analysis of cross-linked complexes from cells labeled to steady state indicates that, in addition to cadherin/catenin complexes, there were cadherin independent pools of catenins present in both the TX-100-soluble and -insoluble fractions. Metabolic labeling followed by chase showed that immediately after synthesis, cadherin/beta-catenin, and cadherin/plakoglobin complexes were present in the TX-100-soluble fraction. Approximately 50% of complexes were titrated into the TX-100-insoluble fraction coincident with the arrival of the complexes at the plasma membrane and the assembly of alpha-catenin. Subsequently, > 90% of labeled cadherin, but no additional labeled catenin complexes, entered the TX-100 insoluble fraction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8207060 TI - A new kinesin-like protein (Klp1) localized to a single microtubule of the Chlamydomonas flagellum. AB - The kinesin superfamily of mechanochemical proteins has been implicated in a wide variety of cellular processes. We have begun studies of kinesins in the unicellular biflagellate alga, Chlamydomonas reinhardtii. A full-length cDNA, KLP1, has been cloned and sequenced, and found to encode a new member of the kinesin superfamily. An antibody was raised against the nonconserved tail region of the Klp1 protein, and it was used to probe for Klp1 in extracts of isolated flagella and in situ. Immunofluorescence of whole cells indicated that Klp1 was present in both the flagella and cell bodies. In wild-type flagella, Klp1 was found tightly to the axoneme; immunogold labeling of wild-type axonemal whole mounts showed that Klp1 was restricted to one of the two central pair microtubules at the core of the axoneme. Klp1 was absent from the flagella of mutants lacking the central pair microtubules, but was present in mutant flagella from pf16 cells, which contain an unstable C1 microtubule, indicating that Klp1 was bound to the C2 central pair microtubule. Localization of Klp1 to the C2 microtubule was confirmed by immunogold labeling of negatively stained and thin sectioned axonemes. These findings suggest that Klp1 may play a role in rotation or twisting of the central pair microtubules. PMID- 8207062 TI - Defining interactions and distributions of cadherin and catenin complexes in polarized epithelial cells. AB - The cadherin/catenin complex plays important roles in cell adhesion, signal transduction, as well as the initiation and maintenance of structural and functional organization of cells and tissues. In the preceding study, we showed that the assembly of the cadherin/catenin complex is temporally regulated, and that novel combinations of catenin and cadherin complexes are formed in both Triton X-100-soluble and -insoluble fractions; we proposed a model in which pools of catenins are important in regulating assembly of E-cadherin/catenin and catenin complexes. Here, we sought to determine the spatial distributions of E cadherin, alpha-catenin, beta-catenin, and plakoglobin, and whether different complexes of these proteins accumulate at steady state in polarized Madin-Darby canine kidney cells. Protein distributions were visualized by wide field, optical sectioning, and double immunofluorescence microscopy, followed by reconstruction of three-dimensional images. In cells that were extracted with Triton X-100 and then fixed (Triton X-100-insoluble fraction), more E-cadherin was concentrated at the apical junction relative to other areas of the lateral membrane. alpha Catenin and beta-catenin colocalize with E-cadherin at the apical junctional complex. There is some overlap in the distribution of these proteins in the lateral membrane, but there are also areas where the distributions are distinct. Plakoglobin is excluded from the apical junctional complex, and its distribution in the lateral membrane is different from that of E-cadherin. Cells were also fixed and then permeabilized to reveal the total cellular pool of each protein (Triton X-100-soluble and -insoluble fractions). This analysis showed lateral membrane localization of alpha-catenin, beta-catenin, and plakoglobin, and it also revealed that they are distributed throughout the cell. Chemical cross linking of proteins and analysis with specific antibodies confirmed the presence at steady state of E-cadherin/catenin complexes containing either beta-catenin or plakoglobin, and catenin complexes devoid of E-cadherin. Complexes containing E cadherin/beta-catenin and E-cadherin/alpha-catenin are present in both the Triton X-100-soluble and -insoluble fractions, but E-cadherin/plakoglobin complexes are not detected in the Triton X-100-insoluble fraction. Taken together, these results show that different complexes of cadherin and catenins accumulate in fully polarized epithelial cells, and that they distribute to different sites. We suggest that cadherin/catenin and catenin complexes at different sites have specialized roles in establishing and maintaining the structural and functional organization of polarized epithelial cells. PMID- 8207064 TI - Perturbation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members. AB - To examine the functions of ERM family members (ezrin, radixin, and moesin), mouse epithelial cells (MTD-1A cells) and thymoma cells (L5178Y), which coexpress all of them, were cultured in the presence of antisense phosphorothioate oligonucleotides (PONs) complementary to ERM sequences. Immunoblotting revealed that the antisense PONs selectively suppressed the expression of each member. Immunofluorescence microscopy of these ezrin, radixin, or moesin "single suppressed" MTD-1A cells revealed that the ERM family members are colocalized at cell-cell adhesion sites, microvilli, and cleavage furrows, where actin filaments are densely associated with plasma membranes. The ezrin/radixin/moesin antisense PONs mixture induced the destruction of both cell-cell and cell-substrate adhesion, as well as the disappearance of microvilli. Ezrin or radixin antisense PONs individually affected the initial step of the formation of both cell-cell and cell-substrate adhesion, but did not affect the microvilli structures. In sharp contrast, moesin antisense PONs did not singly affect cell-cell and cell substrate adhesion, whereas it partly affected the microvilli structures. These data indicate that ezrin and radixin can be functionally substituted, that moesin has some synergetic functional interaction with ezrin and radixin, and that these ERM family members are involved in cell-cell and cell-substrate adhesion, as well as microvilli formation. PMID- 8207066 TI - Isolation and characterization of a novel dynein that contains C and A heavy chains from sea urchin sperm flagellar axonemes. AB - A novel dynein (C/A dynein), which is composed of C and A heavy chains, two intermediate chains and several light chains, was isolated from sea urchin sperm flagella. The C/A dynein was released by the treatment with 0.7 M NaCl plus 5 mM ATP from the axonemes depleted of outer arm 21 S dynein. Sedimentation coefficient of this dynein was estimated by sucrose density gradient centrifugation to be 22-23 S. The C/A dynein particle appeared to be composed of three distinct domains; two globular head domains and one rod domain as seen by negative staining electron microscopy. The mobility of 'A' heavy chain of C/A dynein on SDS-gel electrophoresis was similar to that of A heavy chains (A alpha and A beta) of 21 S dynein. However, UV-cleavage patterns of C and A heavy chains of C/A dynein were different from those of A heavy chains of 21 S dynein. Furthermore, an antiserum raised against A heavy chain of C/A dynein did not crossreact with A heavy chains of 21 S dynein. Under the conditions in which the C/A dynein was released, some of inner arms were removed concomitantly from axonemes as observed by electron microscopy. These results suggested that C/A dynein is a component of the inner arms. PMID- 8207065 TI - Sense and antisense modification of glial alpha B-crystallin production results in alterations of stress fiber formation and thermoresistance. AB - The phenotypic effects of selectively altering the levels of alpha B-crystallin in cultured glial cells were analyzed using sense and antisense approaches. Rat C6 glioma cells and human U-373MG glioma cells were transfected with a rat alpha B-crystallin sense cDNA or an antisense cDNA regulated by a Rous sarcoma virus promoter to alter cellular levels of alpha B-crystallin. The antisense strategy resulted in decreased alpha B-crystallin levels, as revealed by Western blot and immunocytochemical analyses. The reduced alpha B-crystallin expression was accompanied by alterations in cellular phenotype: (a) a reduction of cell size and/or a slender cell morphology; (b) a disorganized microfilament network; and (c) a reduction of cell adhesiveness. Like HSP27, the presence of additional alpha B-crystallin protein confers a thermoresistant phenotype to stable transfectants. Thus, alpha B-crystallin in glioma cells plays a role in their thermal resistance and may contribute to the stability of cytoskeletal organization. PMID- 8207063 TI - Liver-intestine cadherin: molecular cloning and characterization of a novel Ca(2+)-dependent cell adhesion molecule expressed in liver and intestine. AB - A novel member of the cadherin family of cell adhesion molecules has been characterized by cloning from rat liver, sequencing of the corresponding cDNA, and functional analysis after heterologous expression in nonadhesive S2 cells. cDNA clones were isolated using a polyclonal antibody inhibiting Ca(2+)-dependent intercellular adhesion of hepatoma cells. As inferred from the deduced amino acid sequence, the novel molecule has homologies with E-, P-, and N-cadherins, but differs from these classical cadherins in four characteristics. Its extracellular domain is composed of five homologous repeated domains instead of four characteristic for the classical cadherins. Four of the five domains are characterized by the sequence motifs DXNDN and DXD or modifications thereof representing putative Ca(2+)-binding sites of classical cadherins. In its NH2 terminal region, this cadherin lacks both the precursor segment and the endogenous protease cleavage site RXKR found in classical cadherins. In the extracellular EC1 domain, the novel cadherin contains an AAL sequence in place of the HAV sequence motif representing the common cell adhesion recognition sequence of E-, P-, and N-cadherin. In contrast to the conserved cytoplasmic domain of classical cadherins with a length of 150-160 amino acid residues, that of the novel cadherin has only 18 amino acids. Examination of transfected S2 cells showed that despite these structural differences, this cadherin mediates intercellular adhesion in a Ca(2+)-dependent manner. The novel cadherin is solely expressed in liver and intestine and was, hence, assigned the name LI-cadherin. In these tissues, LI-cadherin is localized to the basolateral domain of hepatocytes and enterocytes. These results suggest that LI-cadherin represents a new cadherin subtype and may have a role in the morphological organization of liver and intestine. PMID- 8207067 TI - C/A dynein isolated from sea urchin sperm flagellar axonemes. Enzymatic properties and interaction with microtubules. AB - C/A dynein is a novel dynein isolated from sea urchin sperm flagellar axonemes. It is composed of C and A heavy chains and some additional lower molecular mass polypeptide chains. The characterization of ATPase activity and the interaction of this dynein with microtubules polymerized from calf brain tubulin were investigated in this study. The ATPase activity of C/A dynein (0.3-0.4 mumol Pi/min per mg) was about one half that of outer arm 21 S dynein (0.6-0.8 mumol Pi/min per mg) at 25 degrees C. Vanadate inhibited the ATPase activity with a half-maximal inhibition at 1 microM. C/A dynein absorbed to the glass surface was able to translocate the microtubules towards its plus end. The velocity of the microtubule movement in the presence of 1 mM ATP was 4.0 to 4.5 microns/s at 22 degrees C. C/A dynein binds to and bundles the microtubules even in the presence of ATP. Cross-bridges were found between adjacent microtubules in the bundle with an axial periodicity of about 24 nm. The ATPase activity of C/A dynein was enhanced up to several-fold by the microtubules at concentration as low as 1 mg/ml. On the other hand, 21 S dynein bound to the microtubules with 24 nm axial periodicity only in the absence of ATP. Its ATPase activity was not activated by the microtubules. From these results, it is concluded that the manner of interaction with microtubules of C/A dynein is different from that of the outer arm dynein. PMID- 8207069 TI - Membrane association of cathepsin B can be induced by transfection of human breast epithelial cells with c-Ha-ras oncogene. AB - Alterations in trafficking and increases in expression of the lysosomal proteases cathepsins B, D and L have been observed in transformed cells and malignant tumors, including human breast carcinoma. ras and the related rab proteins participate in the vesicular transport processes required for normal trafficking of lysosomal enzymes. In addition, transfection of murine fibroblasts with the ras oncogene has been shown to increase the expression of cathepsins L and B. As human cancers are primarily epithelial in origin, we have investigated whether there are alterations in the trafficking and expression of cathepsin B in MCF-10 human breast epithelial cells transfected with wild-type and mutated ras. In all cells examined, i.e. mortal MCF-10M cells, immortal MCF-10A or MCF-10F cells, and transfected MCF-10A cells (transfected with the neomycin resistance gene (MCF 10Aneo) or cotransfected with wild-type proto-oncogenic ras (MCF-10AneoN) or mutated oncogenic ras (MCF-10AneoT)), levels of mRNA transcripts for cathepsin B were similar. However, alterations in trafficking of cathepsin B were observed in the cells transfected with oncogenic ras. In these cells there was an increased association of cathepsin B activity and cathepsin B protein with plasma membrane/endosomal fractions and a more peripheral distribution of immunofluorescent staining for cathepsin B. At the electron microscopic level, immunogold labeling for cathepsin B was localized to the cell membrane as well as to vesicles in the microvilli and adjacent to the cell membrane. In the parental MCF-10A cells, in contrast, cathepsin B was localized to vesicles in the perinuclear region. The cathepsin B associated with plasma membrane/endosomal fractions in the cells transfected with oncogenic ras was mature cathepsin B as demonstrated by immunoblot analysis. This was confirmed further by showing an absence of peripheral immunofluorescent staining in these cells using an antibody specific for the propeptide of cathepsin B. Thus, we have demonstrated by multiple techniques that transfection of human breast epithelial cells with oncogenic ras results in alterations in the trafficking of cathepsin B similar to those observed previously in human and animal tumors of both epithelial and mesenchymal origin. PMID- 8207068 TI - Bcl-2 protein localizes to the chromosomes of mitotic nuclei and is correlated with the cell cycle in cultured epithelial cell lines. AB - bcl-2 gene expression confers a survival advantage by preventing cells from entering apoptosis. In contrast to the previously described cytoplasmic localization of Bcl-2 in epithelial cells in vivo, in this study we have demonstrated, in a series of human epithelial cell lines, that Bcl-2 also localizes to mitotic nuclei. Both immunocytochemical and immunoelectron microscopical examinations localize this protein to nuclei and in particular to chromosomes. Nuclear Bcl-2 expression in these cell lines is correlated with the cell cycle. There is relatively strong expression during mitosis, most intense during prophase and metaphase, declining in telophase and then the protein becomes undetectable soon after separation of the two daughter cells. The expression and distribution of Bcl-2 is influenced by treatment with excessive thymidine. These results indicate that Bcl-2 may protect the cells from apoptosis occurring during mitosis and suggest a possible role for the protein in cell immortalization. PMID- 8207071 TI - Heparin stimulates the proliferation of intestinal epithelial cells in primary culture. AB - Heparin is a sulphated glycosaminoglycan derived from mast cells and has a number of functions including the inhibition of proliferation in several cell types and interactions with a range of heparin-binding growth factors. We report that heparin is a trophic factor in primary cultures of rat small intestinal epithelium. Heparin elicits a dose-dependent increase in epithelial proliferation and inhibits the growth of associated mesenchyme. The trophic effect of this molecule is not reproduced by other glycosaminoglycans including heparan sulphate but is dependent upon extensive molecular sulphation. Highly sulphated polysaccharides that are structurally unrelated to heparin (e.g. dextran sulphate and pentosan polysulphate) also stimulate epithelial proliferation in primary cultures. Heparin may act by the potentiation of mesenchyme-derived heparin binding growth factors and these data suggest an in vivo role for mast cell derived heparin in mucosal wound regeneration. PMID- 8207070 TI - Coiled bodies in the nucleolus of breast cancer cells. AB - Coiled bodies are a special type of small round nuclear body, composed of coiled fibers and granules, especially prominent in the nucleoplasm of highly active cells (Brasch and Ochs (1992) Exp. Cell Res. 202, 211-223). Although no specific function has been assigned to coiled bodies, they contain spliceosome snRNAs and proteins, as well as the nucleolar U3 RNA-associated protein fibrillarin. In the present study, we have used antibodies to the coiled body-specific protein p80 coilin, together with double-label immunofluorescence, confocal microscopy and immunoelectron microscopy, to examine the distribution of coiled bodies in a number of different breast cancer cell lines. By immunofluorescence, all cell lines had prominent coiled bodies in the nucleoplasm and several cell lines appeared to have coiled bodies within the nucleolus itself. Double-label immunofluorescence and confocal laser scanning microscopy confirmed the nucleolar localization of coiled bodies. Besides containing p80-coilin, nucleoplasmic and nucleolar coiled bodies contained fibrillarin and Sm proteins. By conventional and immunoelectron microscopy, nucleolar coiled bodies appeared as discrete structures within the nucleolus in a number of different morphotypes, distinct from the normal nucleolar domains of granular component, dense fibrillar component, and fibrillar centers. While the significance of finding coiled bodies in the nucleolus of certain breast cancer cell lines is at present unknown, this represents the first report of coiled bodies and Sm staining in the nucleolus of mammalian cells. PMID- 8207072 TI - Constitutive expression of MHC and adhesion molecules by alveolar epithelial cells (type II pneumocytes) isolated from human lung and comparison with immunocytochemical findings. AB - Highly purified populations of alveolar epithelial cells (type II pneumocytes) were isolated from human lung specimens. These cells were characterised histochemically, by demonstrating the presence of intracellular alkaline phosphatase, and morphologically, by electron microscopic demonstration of lamellar bodies and microvilli. Expression of the epithelial glycoprotein HEA 125, of MHC class I and class II (HLA-DR, -DP and -DQ) antigens and of the intercellular adhesion molecules ICAM-1, VCAM-1, LFA-3 and B7 was quantified by flow cytometry. Comparison was made between the expression of these molecules by isolated type II cells and by alveolar epithelium in normal human lung tissue after immunocytochemical staining of frozen sections of donor lung. Isolated type II pneumocytes expressed HEA-125 and class I MHC molecules and the class II MHC molecules HLA-DR and -DP; HLA-DQ was not detected. The intercellular adhesion molecule ICAM-1 was expressed constitutively at low levels but there was minimal expression of VCAM-1, LFA-3 and B7. It was not possible to differentiate type II cells from the predominant type I pneumocytes on frozen sections. Alveolar epithelium expressed HEA-125, class I MHC antigens, the class II molecules HLA DR, and -DP and the intercellular adhesion molecule LFA-3. Expression of the adhesion molecules ICAM-1, VCAM-1 and B7 was variable. As with the isolates, HLA DQ was not observed on alveolar epithelium. In conclusion, a reproducible method for the isolation of pure populations of human type II pneumocytes has been developed. These cells were not damaged by the isolation procedure. It is not known whether alveolar epithelium can present antigens to T lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207073 TI - Cell cycle redistribution of U3 snRNA and fibrillarin. Presence in the cytoplasmic nucleolus remnant and in the prenucleolar bodies at telophase. AB - The distribution of the U3 small nuclear RNA during the cell cycle of the CHO cell line was studied by in situ hybridization using digoxigenin-labelled oligonucleotide probes. The location of the hybrids by immunofluorescence microscopy and at the ultrastructural level was correlated with the distribution of two nucleolar proteins, nucleolin and fibrillarin. The U3 snRNA molecules persist throughout mitosis in close association with the nucleolar remnant. U3 snRNA is present in the prenucleolar bodies (PNBs) and could participate in nucleologenesis in association with several nucleolar proteins such as nucleolin and fibrillarin. The interaction of U3 snRNP with the 5' external spacer of pre RNA newly synthesized by active NORs is proposed to be the promoting event of nucleologenesis. PMID- 8207074 TI - Induction of fibroblast 92 kDa gelatinase/type IV collagenase expression by direct contact with metastatic tumor cells. AB - Previous studies have correlated release of the 92 kDa type IV collagenase/gelatinase by tumor cells in culture with metastatic potential. We have now demonstrated that the ability of tumor cells that do not express the 92 kDa gelatinase to induce release of this metalloproteinase from normal fibroblasts may also be associated with the metastatic phenotype. A transformed rat embryo cell line, 2.8, failed to release the 92 kDa gelatinase alone in culture, but gave rise to metastatic tumors whose explants contained the 92 kDa gelatinase. In contrast, a non-metastatic transformed cell line, RA3, did not express the 92 kDa gelatinase alone in culture or in tumor explants. To explore the mechanisms that might govern host-tumor cell interactions in this system, we have studied the effects of co-culture of these transformed cell lines with rat embryo fibroblasts (REF) in culture. 92 kDa gelatinase expression was induced by co-culture of 2.8 with REF, but co-culture of the non-metastatic line RA3 with REF did not result in induction of the 92 kDa gelatinase. The 92 kDa gelatinase in these co-cultures was released by the fibroblasts; methanol-fixed 2.8 cells induced 92 kDa gelatinase expression in REF, but fixed REF cells did not induce enzyme expression in 2.8 cells. This suggested that cell contact was required for induction, which was confirmed by showing that 92 kDa gelatinase induction in co culture was abolished by separating REF from 2.8 by solute-permissive membranes. In addition, REF could not be stimulated to produce the 92 kDa gelatinase by 2.8 derived conditioned medium, by 2.8-derived extracellular matrix, or by isolated matrix components. These data indicate that metastatic tumor cells can induce 92 kDa gelatinase expression in fibroblasts through a mechanism dependent upon cell contact. In situ hybridization of nude mouse tumors derived from these transformed cell lines revealed 92 kDa gelatinase expression in the stroma of tumors from 2.8, but not in tumors from RA3. Therefore, the experiments based on in vitro co-culture of tumor cells and fibroblasts, together with the in situ localization of mRNA to host cells, suggest that host production of the 92 kDa gelatinase may occur in response to direct contact with metastatic tumor cells. PMID- 8207075 TI - The effects of age on the response of rabbit periosteal osteoprogenitor cells to exogenous transforming growth factor-beta 2. AB - Additional bone and cartilage are formed if transforming growth factor-beta is injected into the periosteum of calvariae or long bones. To investigate this further, transforming growth factor-beta 2 was injected into the periosteum of the tibia of 3-day-old, 3-month-old and 2-year-old rabbits. In all instances, there was an increase in proliferation of the cells of the cambial layer of the periosteum, that is, the osteoprogenitor cells, and breakdown of the fibrous layer. Oedema was induced in the surrounding connective tissues. Over the experimental period the normal neonatal tibia is undergoing rapid growth; there is periosteal bone formation and endosteal resorption. In the experimental neonatal tibiae, an increase in periosteal bone formation is seen after three injections of 20 ng of transforming growth factor-beta 2, which is accompanied by cartilage after five injections; the amounts of induced bone and cartilage increase with the number of injections. The chondrocytes hypertrophy after 4 days and the cartilage is replaced by bone endochondrally. In contrast, after seven injections of 20 ng transforming growth factor-beta 2, there is only a small amount of new bone on the 3-month-old tibia and none on the 2-year-old tibia. One day after seven injections of 200 ng transforming growth factor-beta 2, there is a small amount of bone formation, while seven days after cartilage is found as small discrete nodules on the 3-month-old tibia, but as small areas within the bone on the 2-year-old tibia. It is concluded that the primary effect of transforming growth factor-beta 2 in this experimental model is to increase the proliferative rate of the osteoprogenitor cells in the periosteum. It is argued that transforming growth factor-beta 2 does not initiate osteoblastic or chondrocytic differentiation of osteoprogenitor cells. It is suggested that their differentiation is controlled by the local environment, in particular, the vascularity and locally circulating growth factors. PMID- 8207076 TI - Lamellipod extension and K+ current in osteoclasts are regulated by different types of G proteins. AB - Osteoclasts are the cells responsible for the resorption of bone and other mineralized tissues. GTP-binding proteins (G proteins) play important roles in regulating the activity of many cell types; however, there is limited knowledge of their functions in osteoclasts. We used the patch-clamp technique in the whole cell configuration to introduce either hydrolysis-resistant guanosine triphosphate analogues or fluoroaluminate into single rat osteoclasts, and examined the effects of G protein activation on cell morphology and ionic conductances. Guanosine 5'-O-(3-thiotriphosphate) or 5'-guanylyl imidodiphosphate, but not the control compounds adenosine 5'-O-(3 thiotriphosphate) or guanosine 5'-O-(2-thiodiphosphate), induced: (1) prompt spreading due to extension of lamellipodia; and (2) after a latency of several minutes, complete suppression of the inwardly rectifying K+ current. Pertussis toxin did not alter either spreading or suppression of K+ current induced by guanosine 5'-O-(3-thiotriphosphate). Cytochalasin D, but not colchicine, prevented guanosine 5'-O-(3-thiotriphosphate)-induced spreading, consistent with actin polymerization underlying lamellipod extension. Whole-cell capacitance did not change during guanosine 5'-O-(3-thiotriphosphate)-induced spreading, which is consistent with a lack of change in total plasma membrane area. Fluoroaluminate did not induce spreading, but it did suppress the K+ current. The differential effects of fluoroaluminate and guanosine 5'-O-(3-thiotriphosphate) suggest that lamellipod extension is regulated by a small molecular mass, monomeric G protein, whereas the inwardly rectifying K+ current is regulated by a large molecular mass, heterotrimeric G protein. Thus, osteoclast motility and ion transport are regulated by separate G protein-coupled pathways. PMID- 8207077 TI - Expression of the integrin alpha 6 beta 4 in peripheral nerves: localization in Schwann and perineural cells and different variants of the beta 4 subunit. AB - Integrin alpha 6 beta 4 is expressed in human peripheral nerves, but not in the central nervous system. This integrin heterodimer has previously been found in perineural fibroblast-like cells and in Schwann cells (SCs), which both assemble a basement membrane but do not form hemidesmosomes. We show here that in SCs, which had formed a myelin sheath, alpha 6 beta 4 was enriched in the proximity of the nucleus, at Ranvier paranodal areas and at Schmitt-Lanterman clefts; alpha 6 beta 4 was also found at the grooved interface between small axons and non myelinating SCs. Immunoprecipitation of human peripheral nerves, in combination with Western blotting showed that beta 4 is associated with the alpha 6A subunit. Northern blot analysis of human peripheral nerves showed a single beta 4 transcript of 6 kb. Using the reverse transcriptase polymerase chain reaction, we detected two mRNA species, one for the most common (-70, -53) form of beta 4 and the other encoding the (+53) variant of beta 4. Cultured SCs were devoid of alpha 6 beta 4 but expressed alpha 6 beta 1, indicating that SCs lose beta 4 expression when contact with neurons is lost. Thus, resting SCs in contact with axons express alpha 6A in combination with beta 4, irrespective of myelin formation. We suggest that alpha 6 beta 4 expressed in SCs plays a role in peripheral neurogenesis. PMID- 8207078 TI - Sorting of a secretory protein (gp80) to the apical surface of Caco-2 cells. AB - We have investigated the synthesis and polarized secretion of the exogenous gp80 glycoprotein complex in the human epithelial adenocarcinoma cell line, Caco-2. gp80 is secreted at the apical surface of Madin-Darby canine kidney (MDCK) cells and should, therefore, display the signal(s) required for sorting into the apical exocytic pathway. In Caco-2 cells, no bona fide secretory protein released preferentially at the apical surface has been described so far. To address the question of whether Caco-2 cells possess a machinery capable of delivery of secretory proteins at the apical surface, we stably transfected the cells with a recombinant gene coding for the gp80 glycoprotein complex. Pulse-chase analysis showed that stably transfected Caco-2 cells secrete gp80 quantitatively into the medium. In polarized layers of filter-grown Caco-2 cells, the protein was secreted predominantly at the apical surface, demonstrating the ability of the cells to efficiently sort secretory proteins directly into the apical exocytic pathway. Our results further demonstrate that the apical targeting information of gp80 recognized by MDCK cells is also recognized by Caco-2 cells. PMID- 8207079 TI - Compartmentalization, processing and redistribution of the plasma membrane protein CE9 on rodent spermatozoa. Relationship of the annulus to domain boundaries in the plasma membrane of the tail. AB - Western blotting, immunofluorescence and immunogold electron microscopy were used to examine the compartmentalization, processing and redistribution of the integral plasma membrane protein CE9 on the spermatozoa of rats, mice and hamsters. In each species examined, spermatozoal CE9 was found to undergo endoproteolytic processing followed by a net redistribution from the posterior tail domain into the anterior-tail domain of the plasma membrane during epididymal maturation. Compared to spermatozoa of the rat and mouse, those of the hamster were found to express a greater proportion of their CE9 within the anterior-tail plasma membrane domain at all stages of maturation. As a consequence, CE9 was judged to be a suitable marker for two different spermatozoal plasma membrane domains: the posterior-tail plasma membrane domain (spermatozoa from the testis and caput epididymidis of the rat and mouse) and the anterior-tail domain (spermatozoa from the cauda epididymidis of the hamster). Immunogold electron microscopy was used to pinpoint the positions of the boundaries of these CE9-containing plasma membrane domains at a high level of resolution. In each case, the position of the CE9 domain boundary was found to be strongly correlated with that of the subplasmalemmal electron-dense ring known as the annulus. The precise spatial relationship between the CE9 domain boundary and the annulus was, however, found to differ significantly among species and/or as a function of maturation. PMID- 8207080 TI - Alternative splicing of human cyclin E. AB - Cyclin E is a regulatory subunit of the cdc2-related protein kinase cdk2, which is activated shortly before S-phase entry, thus defining it as a G1 cyclin. We report here the existence of a 43 kDa splice variant of human cyclin E, termed cyclin Es, which lacks 49 amino acids within the cyclin box compared to the known 48 kDa cyclin E. Cyclin Es is expressed at approximately 1/10 of the level of full-length cyclin E in several cell lines analysed. The two cyclin E forms differ functionally in that cyclin E, but not cyclin Es, is able to complex with cdk2, to activate the histone H1, pRb and p107 in vitro kinase activity of cdk2 and to rescue a triple CLN mutation in S. cerevisiae. Cyclin Es is the first splice variant of a cell cycle regulatory protein to be described. Our findings also indicate that the cyclin box in cyclin E mediates the interaction with cdk2. PMID- 8207081 TI - Reorganization of the centrosome and associated microtubules during the morphogenesis of a mouse cochlear epithelial cell. AB - Reorganization of centrosomal microtubule-organizing centres and the minus ends of microtubules occurs as the centrosomal ends of large microtubule bundles are repositioned and anchored to cell junctions in certain epithelial cells called inner pillar cells in the mouse organ of Corti. The microtubule bundle that assembles in each cell consists of two distinct microtubule arrays that run closely alongside each other. Both arrays are attached to the cell surface at their upper and lower ends. One of the arrays spans the entire length of a cell but the other is confined to its lower portion. Initially, about 3,000 microtubules elongate downwards from an apically situated centrosome in each cell. Subsequently, the minus ends of these microtubules, and the centrosome and its two centrioles, migrate for about 12 microns to the tip of a laterally directed projection. Then, a meshwork of dense material accumulates to link microtubule minus ends and the centrosome to cell junctions at the tip of the projection. Pericentriolar satellite bodies, which form after the initial burst of microtubule nucleation, may represent a condensed and inactive concentration of microtubule-nucleating elements. Surprisingly, as a cell matures, about 2,000 microtubules are eliminated from the centrosomal end of the microtubule bundle. However, about 2,000 microtubules are added to the basal portion of each bundle at levels that are remote with respect to the location of the centrosome. Possibly, these microtubules have escaped from the centrosome. If this is the case, then both the plus and minus ends of most of the errant microtubules are captured by sites at the cell surface where the ends are finally anchored. Alternatively, each cell possesses at least one other major microtubule nucleating site (which does not possess centrioles) in addition to its centrosome. PMID- 8207082 TI - A protein related to brain microtubule-associated protein MAP1B is a component of the mammalian centrosome. AB - The centrosome is the main microtubule organizing center of mammalian cells. Structurally, it is composed of a pair of centrioles surrounded by a fibro granular material (the pericentriolar material) from which microtubules are nucleated. However, the nature of centrosomal molecules involved in microtubules nucleation is still obscure. Since brain microtubule-associated proteins (MAPs) lower the critical tubulin concentration required for microtubule nucleation in tubulin solution in vitro, we have examined their possible association with centrosomes. By immunofluorescence, monoclonal and polyclonal antibodies raised against MAP1B stain the centrosome in cultured cells as well as purified centrosomes, whereas antibodies raised against MAP2 give a completely negative reaction. The MAP1B-related antigen is localized to the pericentriolar material as revealed by immunoelectron microscopy. In preparations of purified centrosomes analyzed on poly-acrylamide gels, a protein that migrates as brain MAP1B is present. After blotting on nitrocellulose, it is decorated by anti-MAP1B antibodies and the amino acid sequence of proteolytic fragments of this protein is similar to brain MAP1B. Moreover, brain MAP1B and its centrosomal counterpart share the same phosphorylation features and have similar peptide maps. These data strongly suggest that a protein homologue to MAP1B is present in centrosomes and it is a good candidate for being involved in the nucleating activity of the pericentriolar material. PMID- 8207083 TI - Nuclear import of the myogenic factor MyoD requires cAMP-dependent protein kinase activity but not the direct phosphorylation of MyoD. AB - MyoD is a nuclear phosphoprotein that belongs to the family of myogenic regulatory factors and acts in the transcriptional activation of muscle-specific genes. We have investigated the role of cAMP-dependent protein kinase (A-kinase) in modulating the nuclear locale of MyoD. Purified MyoD protein microinjected into the cytoplasm of rat embryo fibroblasts is rapidly translocated into the nucleus. Inhibition of A-kinase activity through injection of the specific inhibitory peptide PKI prevents this nuclear localisation. This inhibition of nuclear location is specifically reversed by injection of purified A-kinase catalytic subunit, showing the requirement for A-kinase in the nuclear import of MyoD. Site-directed mutagenesis of all the putative sites for A-kinase-dependent phosphorylation on MyoD, substituting serine or threonine residues for the non phosphorylatable amino acid alanine, had no effect on nuclear import of mutated MyoD. These data exclude the possibility that the effect of A-kinase on the nuclear translocation of MyoD is mediated by direct phosphorylation of MyoD and imply that A-kinase operates through phosphorylation of components involved in the nuclear transport of MyoD. PMID- 8207084 TI - Cytochemical features common to nucleoli and cytoplasmic nucleoloids of Olea europaea meiocytes: detection of rRNA by in situ hybridization. AB - We used light and electron microscopic techniques to study the composition of cytoplasmic nucleoloids during meiotic division in Olea europaea. Nucleoloids were found in two clearly distinguishable morphological varieties: one similar in morphology to the nucleolus, and composed mainly of dense fibrillar component, and another surrounded by many ribosome-like particles. Cytochemical and immunocytochemical techniques showed similar reactivities in nucleoloids and the nucleolus: both are ribonucleoproteic in nature, and possess argyrophillic, argentaffinic and highly phosphorylated proteins. Immunohistochemical techniques failed to detect DNA in either structure. In situ hybridization to a 18 S rRNA probe demonstrated the presence of ribosomal transcripts in both the nucleolus and nucleoloids. These similarities in morphology and composition may reflect similar functionalities. PMID- 8207085 TI - Role of different domains in the self-association of rat nucleoporin p62. AB - We have expressed rat nucleoporin p62 cDNA in Escherichia coli to obtain material for structural and self-association studies. Electron microscopy and circular dichroism spectroscopy are consistent with a rod-shaped molecule with an alpha helical coiled-coil domain at its C terminus and a cross-beta structure at its N terminus, separated by a threonine-rich linker, which has a less-defined secondary structure. Electron microscopy and the solubility properties of fragments produced using thrombin and CNBr digestion indicate that p62 molecules associate to form linear chains and that a small region near the C terminus is an important determinant of assembly. This association may have important consequences for pore structure and function; for example, one way p62 could associate would be to form rings in nuclear pores that could function like barrel hoops. PMID- 8207086 TI - Site of transcription of ribosomal RNA and intranucleolar structure in HeLa cells. AB - Sites of transcription of ribosomal RNA in HeLa cells were visualized by electron microscopy. Cells were either incubated with Br-uridine, or permeabilized and then incubated with BrUTP, before sites containing Br-RNA were immunolabeled with gold particles. Short incubations ensured that most incorporated analogue remained at synthetic sites. Fibrillar centres were unlabelled except at their periphery; label was concentrated over certain regions of the surrounding dense fibrillar component. These results suggest that the dense fibrillar component is the site of rRNA transcription. After dispersing the granular component and the dense fibrillar component by a hypotonic treatment, removal of most chromatin and preparation of resinless sections, fibrillar centres remained fixed to a nucleoskeleton. These structural and functional features are incorporated into a model for rRNA transcription. PMID- 8207087 TI - The photosynthetic endosymbiont in cryptomonad cells produces both chloroplast and cytoplasmic-type ribosomes. AB - Cryptomonad algae contain a photosynthetic, eukaryotic endosymbiont. The endosymbiont is much reduced but retains a small nucleus. DNA from this endosymbiont nucleus encodes rRNAs, and it is presumed that these rRNAs are incorporated into ribosomes. Surrounding the endosymbiont nucleus is a small volume of cytoplasm proposed to be the vestigial cytoplasm of the endosymbiont. If this compartment is indeed the endosymbiont's cytoplasm, it would be expected to contain ribosomes with components encoded by the endosymbiont nucleus. In this paper, we used in situ hybridization to localize rRNAs encoded by the endosymbiont nucleus of the cryptomonad alga, Cryptomonas phi. Transcripts of the endosymbiont rRNA gene were observed within the endosymbiont nucleus, and in the compartment thought to represent the endosymbiont's cytoplasm. These results indicate that the endosymbiont produces its own set of cytoplasmic translation machinery. We also localized transcripts of the host nucleus rRNA gene. These transcripts were found in the nucleolus of the host nucleus, and throughout the host cytoplasm, but never in the endosymbiont compartment. Our rRNA localizations indicate that the cryptomonad cell produces two different of sets of cytoplasmic type ribosomes in two separate subcellular compartments. The results suggest that there is no exchange of rRNAs between these compartments. We also used the probe specific for the endosymbiont rRNA gene to identify chromosomes from the endosymbiont nucleus in pulsed field gel electrophoresis. Like other cryptomonads, the endosymbiont nucleus of Cryptomonas phi contains three small chromosomes. PMID- 8207088 TI - The regulation of chemotaxis and chemokinesis in Dictyostelium amoebae by temporal signals and spatial gradients of cyclic AMP. AB - The tactic and kinetic locomotion of Dictyostelium discoideum amoebae were examined in cyclic AMP (cAMP) spatial gradient and temporal signal fields. The distributions of migrating cells were examined within 150 microns-thick micropore filters after incubation with different cAMP concentrations, [cAMP], applied in three ways across the fields: as positively or negatively developing gradients, generated either by increasing or decreasing the [cAMP] on one side of the filter, respectively, or as static, linear gradients after negative development. Chemotaxis was only induced by oriented, temporally increasing [cAMP]. Pulses propagated by molecular diffusion or mechanical flow were equally effective. Negatively developing cAMP gradients had no initial effect on cell accumulation. However, if the subsequent static spatial gradient was maintained by an infusion system, some gradients also induced cell accumulation, whose degree and direction depended on the gradient [cAMP]. The basis of this new effect was examined by tracking individual cells by computer-assisted videomicroscopy during locomotion in different [cAMP]. Cells produced a triphasic [cAMP]-dependent response, with optimal cell motility induced by 10-30 nM. The results demonstrate that cell accumulation either up-field or down-field in spatial gradients is governed by the field locations of the attractant concentrations that induce the relative locomotory maxima and minima in the gradient field. Cells perceive the ambient [cAMP], but cannot read the spatial gradient orientation in static or yet steeper regions of developing gradients. Accumulation in static spatial gradients is a function of klino- and orthokinesis, but chemotaxis requires an oriented cAMP pulse or impulse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207089 TI - Tissue-specific expression of the fibril-associated collagens XII and XIV. AB - Interstitial collagen fibrils form the supporting scaffold of all connective tissues. The synthesis of this framework is subject to a precise spatial and temporal regulation in order to meet the mechanical needs of every tissue type. A subgroup of non-fibrillar collagens termed FACIT seems to play a role in this regulation by providing specific molecular bridges between fibrils and other matrix components. Collagens XII and XIV represent such FACIT molecules and occur preferentially in tissues containing banded type I collagen fibrils. We have used the techniques of indirect immunofluorescence and in situ hybridization to investigate the expression patterns of the two molecules during chicken embryonic development. We detected specific differences in these patterns, which may be related to the respective functions of the two proteins within the connective tissues. Collagen XIV was expressed at very few sites in the 6-day-old embryo, but occurred in virtually every collagen I-containing tissue (skeletal muscle, cardiac muscle, gizzard, tendon, periosteum, nerve) by the end of embryonic development. In contrast, collagen XII was fairly abundant in the 6-day-old embryo but was, at later stages, restricted to only a few dense connective tissue structures (bone, tendon, gizzard). Thus, our results suggest that collagen XII and collagen XIV serve different functions during embryonic development although their structures are highly similar. PMID- 8207090 TI - Tubulin and tektin in sea urchin embryonic cilia: pathways of protein incorporation during turnover and regeneration. AB - Axonemal precursor tubulin is the major protein component of the detergent soluble membrane/matrix fraction of sea urchin embryonic cilia. Its unusual abundance may reflect the rapid turnover of these cilia, a process that is further documented here. However, whether during induced regeneration or normal turnover and growth, most other newly synthesized axonemal proteins are not detectable in the membrane/matrix fraction, raising the question of how non tubulin precursors transit the growing cilium to the distal tip where assembly is generally thought to occur. Three potential explanations were considered: (1) the assembly of these components is proximal; (2) their relative concentration is too low to detect; or (3) tubulin alone is conveyed via a membrane/matrix pathway while most other axonemal proteins are transported in association with the axoneme. Light microscope autoradiography of axonemes pulse-chase labeled with [3H]leucine showed relatively uniform labeling, with no evidence for proximal incorporation. Fully grown cilia and cilia at early stages of regeneration were isolated from labeled embryos, fractionated into membrane/matrix, axonemal tubulin and architectural remnant components, and their labeled protein compositions were compared. Heavily labeled axonemal proteins, most notably the integral microtubule doublet component tektin-A, were not detected in the membrane/matrix fraction of emerging cilia, even though nearly half of the total ciliary tubulin appeared in that fraction, arguing against membrane-associated or soluble matrix transit for the architectural proteins at low concentrations. However, after thermal fractionation of axonemes from growing cilia, labeled proteins characteristic of the architectural remnant dominated the solubilized microtubule fraction, supporting axoneme-associated transport of the non-tubulin proteins during growth, in contrast to a membrane/matrix pathway for tubulin. PMID- 8207091 TI - Protein composition of cornified cell envelopes of epidermal keratinocytes. AB - Terminally differentiated mammalian epidermal cells are lined with a 15 nm thick layer of proteins cross-linked by isodipeptide and disulfide bonds, called the cornified cell envelope (CE). A number of proteins, including involucrin, loricrin, cystatin A, filaggrin, a cysteine-rich protein (CRP) and the 'small proline-rich' proteins (SPRRs) have been reported to be components of this complex, but little information has been obtained as to their relative abundances because the acute insolubility of the CEs has precluded direct methods of analysis. To address this question, we have determined the amino acid compositions of isolated CEs, and then modelled them in terms of linear combinations of the candidate proteins. The results show that stratum corneum CEs have a loricrin content of 65-70% (w/w) in human, and 80-85% in mouse. In human epidermal CEs, the secondary contributors are filaggrin and CRP (each approximately 10%), with smaller amounts of involucrin, SPRR and cystatin A (2-5% each) also present. Mouse epidermal CEs have about the same amount of filaggrin and somewhat more SPRR, but only trace amounts of the other proteins. In marked contrast, the major constituents of the CEs of cultured keratinocytes induced to terminal differentiation in vitro are cystatin A, involucrin and CRP (each approximately 30%). No significant amount of loricrin was detected except in sloughed mouse cells, which represent a more advanced state of terminal differentiation than attached cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207092 TI - Ammonia hypersensitivity of slugger mutants of D. discoideum. AB - The weak base ammonia inhibits aggregation and culmination of wild-type amoebae of Dictyostelium discoideum. Here we have examined its effect on a series of 'slugger' mutants previously assigned to 10 complementation groups, and so-called because they remain as slugs for extended periods. We show that the mutants accumulate normal levels of ammonia and hence may be abnormally susceptible to the ammonia they produce. In agreement with this we find that representatives of the slugger complementation groups are hypersensitive to ammonia inhibition at three clearly recognisable morphological stages of development: aggregation, tip formation and culmination. This finding suggests that a common ammonia-sensitive process underlies each of these developmental events. PMID- 8207093 TI - Characterisation of the paxillin-binding site and the C-terminal focal adhesion targeting sequence in vinculin. AB - Paxillin and vinculin are cytoskeletal proteins that colocalise to focal adhesions, specialised regions of the cell involved in attachment to the extracellular matrix. These two molecules form part of a complex of proteins that link the actin network to the plasma membrane. Paxillin has been shown to bind directly in vitro to the C-terminal region of vinculin (Turner et al. (1990). J. Cell Biol. 111, 1059-1068), which also contains a focal adhesion targeting sequence (Bendori et al. (1989). J. Cell Biol. 108, 2383-2393). In the present study, we have used a series of vinculin deletion mutants to map more precisely the sites in vinculin responsible for paxillin binding and focal adhesion localisation. A glutathione-S-transferase fusion protein spanning vinculin residues 881-1000 was sufficient to support 125I-paxillin binding in a gel-blot assay while no detectable binding was observed to a fusion protein spanning residues 881-978. Transfection experiments using cDNAs encoding chick vinculin residues 398-1066 and 398-1028 demonstrated that amino acids C-terminal to residue 1028 were not necessary for targeting to focal adhesions. In contrast, a vinculin polypeptide expressed from a cDNA encoding residues 398-1000 failed to localise to focal adhesions in stably transfected NIH3T3 cells. We have therefore identified a region of 50 amino acids (residues 979-1028) within the C-terminal region of vinculin that contains both the paxillin-binding site and the focal adhesion targeting sequence. This region is highly conserved in human and chicken vinculin and is likely to be important in regulation of the assembly of focal adhesions. PMID- 8207094 TI - On the molecular mechanism of the circadian clock. The 41,000 M(r) clock protein of Chlorella was identified as 3-phosphoglycerate kinase. AB - A 41,000 M(r) polypeptide of Chlorella exhibits a circadian rhythm in its synthesis and possesses characteristic features of a putative essential clock protein as was proposed by the coupled translation-membrane model. Purification of this polypeptide and a microsequencing analysis yielded a N-terminal sequence of 35 amino acids that showed no homology to known sequences that were thought to be involved in circadian rhythm such as the per gene of Drosophila and the frq gene of Neurospora. However, strong homology was observed to 3-phosphoglycerate kinase (PGK) of different organisms. The highest homology (83%) of this Chlorella sequence was found with the PGK of wheat chloroplast. PGK activity and the 41,000 M(r) polypeptide co-purified through differential centrifugation and gel filtration. These data, and comparison with the physical properties of other known PGK molecules, support the conclusion that the 41,000 M(r) polypeptide of Chlorella, a candidate for a putative essential clock protein, is 3 phosphoglycerate kinase. PMID- 8207095 TI - [Schwannoma of the small intestine revealed by hypochromic anemia]. PMID- 8207096 TI - [Volvulus of the superior mesenteric area and congenital variation of the colonic fixation. Human Ontogenesis and Physiopathology. Apropos of a case in an adolescent]. AB - Volvulus of the superior mesenteric territory involving the left and transverse colon is rare. Congenital variations of intestinal fixation have been implicated. We report a case observed in an adolescent which illustrates this hypothesis. There was a fixation of pancreatosplenic region and the left colic angle. The duodenopancreas and the right, transverse and left colon were mobile. Human ontogenesis of the colon could provide a pathophysiologic explanation. During foetal development, the intestine results from unequal growth of the different segments which undergo pressure from the different intra-abdominal contents. The fixation of the different parts of the intestine are independent from each other. Specific circumstances are required for variations in congenital fixation of the colon to led to late events responsible for mechanical volvulus. PMID- 8207097 TI - [Heterotopic experimental liver transplantation with portal revascularization of the graft on the distal splenic vein of the recipient]. AB - A model of heterotopic liver transplantation had been studied. The graft was laid under the recipient liver and the portal blood flow was supplied by anastomosis with the distal part of the splenic vein. Both liver can then receive portal blood through two parallel portal circulation. Liver function of transplant was satisfactory at three months after transplantation. Their had been no alteration of the recipient liver during the same period. PMID- 8207099 TI - [Cuniculatum carcinoma. 6 cases and review of the literature]. AB - The cuniculatum carcinoma is a rare type of epidermoid carcinoma. We report 6 cases with different localizations ("oral cavity and larynx", vulva, lower limb) treated over a 23-year period. Diagnosis is particularly difficult and requires careful clinical examination completed by deep surgical biopsy for histology. The aetiology of the tumour is not well defined. It presents as a slow growing wart with local malignancy and chronic suppuration. Extension to lymph nodes is rare. Histologically there is proliferative deep malpighian infiltration with an aspect of normal cell maturation. Galeries are hollowed out giving the aspect of a rabbit burrow (cuniculatum). Surgery is the only treatment, generally without lymph node curage. Radiotherapy is contraindicated due to anaplastic transformation. PMID- 8207098 TI - [Predictive factors of nodular recurrence after thyroidectomy for goiter]. AB - We report a retrospective series of 44 recurrences of nodular goitre following 430 partial thyroidectomies over a 10 years period. There were 40 women and 4 men with a mean age of 43 and 37 years respectively. Twenty-four recurrences were from our institution (6%) and 20 were referred to us. The median follow-up of primary thyroidectomies was 8.5 years for patients with recurrence and 4 years for patients free of recurrence (p < 10(-6)). The incidence of recurrence was analysed in a statistical and actuarial model considering clinical intra operative and post-operative variables. The following risk-factors for recurrence were found: age < 50 years (p < 0.01), family history of goitre (p < 0.04), unilateral multinodularity (p < 0.0002), diffuse and bilateral distribution of nodules (p < 0.02), atypical resections with conservation of isthmus (p < 0.0001), scintigraphically "warm" nodules (p < 0.001). Interestingly, sex, heterogeneous thyroid parenchyma without macroscopic nodules and the use of post operative levothyroxine did not modify the risk of recurrence. Thirty-three patients were non symptomatic. Thirty-four patients underwent re-operation. Three primary non suspected carcinomas were found. There was no mortality related to re operation. There were not definitive vocal cord paralysis or hypocalcemia. There was no significant difference in vocal or parathyroid morbidity when total thyroidectomy for primitive goitre was compared to total thyroidectomy as re operation. Long-term and periodic follow-up is necessary to detect non symptomatic recurrences in a high-risk population. Total thyroidectomy is the treatment of choice for bilateral multinodular goitre.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207100 TI - [Three-way tube for lavage and active aspiration for prevention and treatment of colorectal disunion and for surgery of acute necrosis of the pancreas]. AB - We conceived and used from 1985 to 1992 a three-way trans-anastomotic tube for 183 left colectomies in order to prevent the disunion of colorectal anastomoses, and also to actively contribute to their treatment. The three-way lavage and aspiration tube was positioned during the suture of the anastomosis. One hundred and nine pre-tube anastomoses served as controls. Major intra-sub or entirely sub peritoneal resections were performed in 94.61% of the cases. The number of disunions decreased from 4.85% to 1.09% including two cases with very low anastomosis with defective sutures. From July 1988 to 31 December 1992 there were no disunions in the 137 last anastomoses. The number of abdomino-perineal amputations was reduced from 81/109 resections in the pre-tube period to 37/183 in the with-tube period, i.e. from 42.63% to 16.81%. All of the disunions healed within 12-18 days. The length of hospitalization declined from 19-20 days to 11.6 days (11 days in the last 137 cases). We also used a three-way tube in 9 cases of acute necrosis of the pancreas. These cases require surgery as soon as possible. With or without sequestrectomy. All nine of our cases were discharged after successful treatment between day 14 and 39, and all returned to normal activities, with the exception of persistent diabetes in one. Secondary operations were never required. PMID- 8207101 TI - [An unusual case of clear-cell carcinoma of the pancreas]. AB - This case of clear-cell carcinoma of the pancreas was a rare for three reasons: a) discovery: the investigation was indicated after sudden digestive hemorrhage revealed by melena and anaemia; b) morphology: the tumour began in the head with a spheric tumoural bud and a pediculated extension into the duodenum; c) pathology a clear-cell tumour similar to the type seen in renal localizations. Only one other case of such a primitive tumour was found reported in the literature. PMID- 8207102 TI - [Typhus perforation in the tropics. Apropos of 83 cases]. AB - Peritonitis due to typhus is still frequent in Vietnam. We studied retrospectively 83 cases of 83 patients operated for peritoneal perforations due to typhus between January 1986 and December 1987. There were more males than females (56 versus 27) and most of the patients were under 30 years of age (72.2%). The diagnosis was made on the basis of clinical picture of fever associated with peritonitis and ileal lesions seen at laparotomy. Treatment for most patients included surgical exeresis, suture of the perforation and lavage and draining of the abdominal cavity. Fifteen patients died during the perioperative period (18% operative mortality). There were 76 cases of post operative complications involving 55 patients. The most frequent complication was parietal infection observed in 55 cases (66.3%). The most severe complication was suture failure seen in 5 cases, 4 of which had a fatal outcome. Operative delay was a statistically significant factor of prognosis. In the specific situation of our clinical experience, simple suture or suture excision remain the most adapted and effective modes of treatment. PMID- 8207103 TI - [Acute pancreatitis caused by varicella-zoster virus after liver transplantation]. AB - Twenty-six days after liver transplantation for primary biliary cirrhosis, a 52 year-old patient was rehospitalized for viral infection. The clinical features were fatigue, anorexia and vomiting. On physical examination, vesicular skin lesions involving the left 8 th intercostal space were suggestive of herpes zoster infection. The following day the patient was extremely tired and dyspnoeic. The abdomen was distended with moderate abdominal epigastric pain. The clinical picture worsened rapidly and the patient died a few hours later. Autopsy revealed acute haemorrhagic necrosis of the pancreas due to herpes-zoster virus. PMID- 8207104 TI - [Partial splenectomy in thalassemia major. Apropos of 19 cases]. AB - Nineteen cases of B Thalassemia have benefited from partial splenectomy at the General Surgery Service of Farhat Hached Hospital in Sousse (Tunisia). The partial splenectomy indication was to reduce hypersplenism, thus transfusion needs, to suppress splenic pain and to conserve a splenic remnant, which preserves patients' immunity. The operation was in reality a subtotal splenectomy keeping the lower pole in all cases. We had no per-operatory complication. The preoperatory bleeding was not more serious than in total splenectomy. In all the patients, we noticed reduction of about half the transfusion need, except one who had also a chronic deficit in glyco-six phospho-dehydrogenase. The average hemoglobin rate increased from 60 g/L in the pre-operatory to 80 g/L after the operation. Consequently, this reduction of transfusion needs results in the decrease of the hemochromatosis, which is one of the main complications of hypertransfused thalassemia. PMID- 8207105 TI - Case in point. Struvite stones (staghorn calculi) due to chronic urinary tract infection. PMID- 8207106 TI - Literature supports THC as therapy. PMID- 8207107 TI - The cause of cirrhosis. PMID- 8207108 TI - In the service of the IRS. PMID- 8207109 TI - Splenectomy: who, when, and why? PMID- 8207111 TI - Medicine for the outdoors. PMID- 8207110 TI - Melanoma: 1. Clinical characteristics. AB - The disease is perhaps the clearest instance of a cancer for which early treatment is crucial. Increasing knowledge of risk factors (including brief, intense sun exposure and sunburn damage early in life) aids the identification of persons at highest risk--one reason for physicians not to be pessimistic about the value of urging patients to limit their sun exposure. PMID- 8207112 TI - Polyarthritis in an elderly man with bladder cancer. PMID- 8207113 TI - Evaluation and treatment of hypercalcemia. PMID- 8207115 TI - Ozone depletion and public health. PMID- 8207114 TI - Syncope in an elderly woman. PMID- 8207116 TI - Case in point. Scurvy. PMID- 8207117 TI - Neonatal lymphocyte subpopulations of the cases with neural tube defects. AB - Neural tube defects (NTDs) are among the most common congenital malformations of central nervous system and are frequently associated with other organ system abnormalities. In order to evaluate the immunological changes in such patients, we examined the lymphocyte subpopulations of 13 newborns with NTDs and 32 healthy newborns. Leukocyte counts, absolute neutrophil and lymphocyte counts were lower in the babies with NTDs. Also the lymphocyte subpopulations such as percentages and absolute counts of T-cells, CD4+ cells, and CD45+ cells showed statistically significant decreases. These findings suggest that the affected babies are immunosuppressed. PMID- 8207118 TI - BALB/c substrain differences in susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease. AB - We report differences among BALB/c substrains in susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease, an immune mediated inflammatory demyelinating disease and experimental model for human multiple sclerosis. BALB/cJ and BALB/cAnNCr mice are susceptible, while BALB/cByJ and BALB/cCum are resistant. Hybrids between BALB/cBy and BALB/cAnNCr were intermediate, although closer to the resistant parent. Backcrosses gave results compatible with differential susceptibility being related to a single segregating locus. Exposure of resistant BALB/cByJ mice to low dose irradiation, 2 days prior to infection, rendered them susceptible to TMEV-induced demyelination. The susceptibility pattern of TMEV-induced demyelinating disease among BALB/c substrains is distinct from those of several autoimmune disorders. PMID- 8207119 TI - Increased levels of soluble tumor necrosis factor receptor in patients with multiple sclerosis and HTLV-1-associated myelopathy. AB - Tumor necrosis factor-alpha (TNF-alpha) is a potent mediator produced by activated T lymphocytes and macrophages, which may play a role in the pathogenesis and development of multiple sclerosis (MS) and HTLV-1-associated myelopathy (HAM). The first step in the induction of many biological effects elicited by TNF-alpha is its binding to specific cell surface receptors. A soluble form of TNF receptor (sTNF-R) can be detected in the body fluid. We measured sTNF-R levels in the sera and cerebrospinal fluid (CSF) of patients with either MS or HAM, and evaluated the correlation between this mediator and disease activity. The levels of sTNF-R in the sera and CSF of patients with MS were significantly increased compared with controls, particularly patients with acute relapsing MS during an exacerbation (P < 0.001). CSF levels of sTNF-R showed a strong correlation with those of TNF (r = 0.716, P < 0.001). Higher levels of sTNF-R in the sera of HAM patients were detected as compared with those of either controls (P < 0.001) or non-HAM carriers (P < 0.001). Patients with HAM exhibited significantly higher CSF levels of sTNF-R than those with other neurological diseases (P < 0.0001). These results suggest that the detection of sTNF-R in the sera and CSF may predict disease progression. Availability of such a marker would be useful in monitoring disease activity. PMID- 8207120 TI - A transgenic mouse model to assess the interaction of cytotoxic T lymphocytes with virally infected, class I MHC-expressing astrocytes. AB - Astrocytes provide crucial support for neurons and their impairment by viruses or their interactions with anti-viral or autoimmune responses could contribute to neurological disease. We have developed a transgenic mouse model to assess lymphocyte-astrocyte interactions. The major histocompatibility complex (MHC) class I molecule, Db, was expressed in astrocytes under the transcriptional control of regulatory sequences from the glial fibrillary acidic protein (GFAP) gene. Baseline cerebral MHC class I mRNA levels from transgenic mice were elevated over those of non-transgenic controls, and a prominent increase in cerebral MHC class I expression occurred following focal, injury-induced astroglial activation within transgenic brains but not in non-transgenic controls. FACS analysis of explant astrocyte cultures from established transgenic lines demonstrated astroglial expression of the GFAP-Db fusion gene at the protein level. Functional antigen-presenting capacity was conferred by the Db transgene, as virus-infected primary astrocytes obtained from transgenic BALB/c mice (KdIdDdLd) expressing the Db molecule were lysed by Db-restricted anti-viral CTL. PMID- 8207121 TI - Theiler's virus is eliminated by a gamma-interferon-independent mechanism in the brain. AB - The intravenous infection of Theiler's virus GD VII strain causes acute encephalomyelitis in infected mice. To determine the cellular mechanism of resistance and interferon (IFN)-gamma-producing cell populations, mononuclear cells isolated from tissues of the brain were analyzed by the flow cytometry method. Antibodies specific for CD3, CD4, CD8, T cell receptor (TCR)-alpha beta, and Asialo GM1 were used to deplete the corresponding cell populations in Theiler's virus-infected mice. CD4+ lymphocytes and CD8+ lymphocytes infiltrated in the brains of infected mice from 5 days postinfection (p.i.). The number of CD3+/TCR-gamma delta+ lymphocytes increased in the brains on Day 6 p.i. The elimination of CD3+ lymphocytes or CD4+ lymphocytes augmented viral replication and suppressed the production of IFN-gamma. The suppression of IFN-gamma production by anti-CD3 monoclonal antibody (mAb) persisted, although the suppression by anti-CD4 mAb was observed only on Day 6 p.i. The depletion of CD8+ lymphocytes as well as TCR-alpha beta+ lymphocytes also augmented the viral replication; however, it did not alter the production of IFN-gamma. Anti-Asialo GM1 antibody had no effect on viral replication and IFN-gamma production. These results indicate that T lymphocytes are important for eliminating Theiler's virus from the brain, CD3+/CD4+/CD8- lymphocytes and CD3+/TCR alpha beta-/CD4-/CD8- lymphocytes would produce IFN-gamma in brain. However, from the result on the experiment of the depletion of TCR-alpha beta+ lymphocytes, the defence mechanisms by T lymphocytes against Theiler's virus would be independent of endogenous IFN-gamma production. PMID- 8207122 TI - Cytokines in the central nervous system: expression of macrophage colony stimulating factor and its receptor during development. AB - To investigate the potential role of cytokines in the development of the central nervous system, we analyzed the production of cytokine mRNA transcripts by S1 nuclease protection analysis in the brains of Swiss-Webster mice during fetal development and after birth. Cytokines studied were interleukin (IL)-1 alpha, IL 2, IL-3, IL-4, IL-5, IL-6, IL-7, macrophage-colony stimulating factor (M-CSF), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and leukemia inhibitory factor (LIF). Only mRNA transcripts for M-CSF were found to be produced constitutively in normal brain tissue. These transcripts were detected continuously from embryonic day (ED) 13 through adulthood. Transcripts encoding the M-CSF receptor (c-fms) were also detected at all of these time points. Despite identification of M-CSF transcripts in the brains of normal mice during development and M-CSF protein in cell cultures, neuropathological examination of the brains of op/op mice, a naturally occurring mouse mutant defective in the production of functional M-CSF, showed no cytoarchitectural abnormalities. PMID- 8207123 TI - A comparison of synapses onto the somata of intrinsically bursting and regular spiking neurons in layer V of rat SmI cortex. AB - Regular spiking (RS) and intrinsically bursting (IB) neurons show distinct differences in their inhibitory responses. Under various conditions, the synaptic responses of RS cells display marked inhibitory postsynaptic potentials (IPSPs), whereas the responses of most IB cells do not (Silva et al: Soc Neurosci Abstr 14:883, 1988; Chagnac-Amitai and Connors: J Neurophysiol 61:747, 62:1149, 1989; Connors and Gutnick: TINS 13:99, 1990). This investigation is designed to determine if differences in the inhibitory responses of RS versus IB cells are reflected in differences in the concentration of inhibitory synapses onto their somata. RS and IB neurons in rat somatosensory cortex were identified by using intracellular recording and labeling, examined with the light microscope, and then serial thin-sectioned prior to examination with the electron microscope. Axonal terminals presynaptic to their somata and proximal dendrites were identified and classified according to criteria described by Peters and coworkers (Peters et al: J Neurocytol 19:584, 1990; Peters and Harriman: J Neurocytol 19:154, 1990; 21:679, 1992). The locations of these boutons were displayed on the surfaces of 3-D reconstructions of the somata and proximal dendrites. The reconstructions were produced directly from the serial thin sections by using a novel, electron microscopic, image-processing computer resource. Our analysis showed no significant difference in the types and concentration of boutons presynaptic to the cell bodies and proximal dendrites of intrinsically bursting versus regular spiking neurons. We conclude that the differences observed in the inhibitory responses of intrinsically bursting versus regular spiking neurons cannot be explained by differences in the concentrations of synapses onto their somata. PMID- 8207124 TI - Quantitative analyses of neuroepithelial cell shapes during bending of the mouse neural plate. AB - Despite a wealth of information about cell behaviors contributing to neurulation in chick embryos, similar behaviors in mouse embryos have yet to be well characterized. This study examines cell behaviors occurring during bending of the mouse neural plate, in particular, qualitative and quantitative changes in neuroepithelial cell shape. Our current results demonstrate that in mouse embryos 1) the median hinge point (MHP), a localized region of neural plate that becomes anchored to the underlying prechordal plate mesoderm or notochord/notochordal plate and forms a midline longitudinal furrow around which folding of the remaining neural plate (i.e., the part of the neural plate not involved in MHP formation) occurs, develops during stages of neural fold elevation; 2) the MHP is enriched with wedge-shaped neuroepithelial cells but has significantly fewer spindle-shaped, inverted wedge-shaped, and globular neuroepithelial cells than do the adjacent paired lateral areas of the neuroepithelium (L); and 3) each L is enriched with spindle-shaped, inverted wedge-shaped, and globular neuroepithelial cells but has significantly fewer wedge-shaped neuroepithelial cells than does the MHP. Thus wedging of neuroepithelial cells occurs during bending of the mouse neural plate and is localized to the MHP during neural fold elevation. Similarly, previous studies in the chick have shown that neuroepithelial cells become wedge shaped during bending of the neural plate and that such cell wedging is localized to the MHP during neural fold elevation. Such studies also have shed light on the roles of MHP formation and localized wedging of neuroepithelial cells within the MHP in the chick; however, such roles have yet to be elucidated in the mouse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207125 TI - Evidence that sympathetic preganglionic neurones are arranged in target-specific columns in the thoracic spinal cord of the rat. AB - It is recognised that selective activation of different target-specific sympathetic preganglionic neurones forms the basis of many autonomic responses. The anatomical basis for this could be the spatial arrangement of these neurones in the spinal cord nuclei. The present study tested this possibility in the rat by determining the location in single animals of three distinct groups of sympathetic preganglionic neurones, one group projecting to the superior cervical ganglion, another to the stellate ganglion and one to the adrenal medulla. Sympathetic preganglionic neurones to each of these targets were simultaneously labeled with fluorescent dyes, either Fluorogold, Fast Blue, or Diamidino Yellow. The numbers and general morphology of the neurones were similar to previous descriptions, and they were distributed in four subnuclei, the nucleus intermediolateralis pars principalis, the nucleus intermediolateralis pars funiculus, the nucleus intercalatus spinalis, and the nucleus intercalatus spinalis pars paraependymalis. It was shown that all three groups of neurones were represented in the more medial sympathetic nuclei, but in the nuclei at the lateral border of the intermediate grey matter each one of the three groups of neurones occupied a discrete location. Adrenal medullary sympathetic preganglionic neurones occupied a lateral aspect, the superior cervical ganglion sympathetic preganglionic neurones a medial aspect, and the stellate ganglion sympathetic preganglionic neurones a space between. Some sympathetic preganglionic neurones were double labeled after dye injections into the superior cervical and stellate ganglion thus indicating that they projected to both ganglia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207126 TI - Interplay between the dendritic trees of alpha and beta ganglion cells during the development of the cat retina. AB - We have analyzed the effect of a small lesion to the retina of a two-day-old kitten and observed that after degeneration of ganglion cells whose axons were severed, a restricted region of the retina remained depleted of cells. Cells located near the borders of the depleted zone showed an abnormal elongation of dendrites towards the bare area. By means of a computer-aided system, we analyzed the whole population of cells at the two borders, and in agreement with previous data found that the effect was most prominent at the border and progressively decreased to eventually disappear at a distance of approximately 500 microns. The distance from the border, however, is not the only factor to influence the degree of asymmetry; with comparable distances, the vicinity of an alpha-cell reduces the projection of the beta-cell dendrites toward the empty area. We suggest that the organization of the adult retinal pattern is also influenced by interactions occurring between dendrites of different classes of ganglion cells. PMID- 8207127 TI - Ventral root avulsion: an experimental model of death of adult motor neurons. AB - The present study proposes a reproducible model of experimental degeneration of adult motor neurons in the rat. Avulsion of ventral roots in the adult lumbar cord transects motor axons at the root exit and leads to retrograde cell death of 80% of motor neurons 2 weeks later; this result follows a series of retrograde changes, including chromatolysis, loss of transmitter phenotype, and accumulation of phosphorylated neurofilaments in perikarya. Glial cells recruited at the site of retrograde injury express both microglia-specific epitopes (as exemplified by OX-42 immunoreactivity) and macrophage-specific markers (e.g., ED-1 immunoreactivity). Macrophage-specific markers become particularly intense 7 days postaxotomy and provide additional evidence of active phagocytosis of injured neurons. Ventral root avulsion is a very useful model for assessing mechanisms of motor neuron death and testing the ability of trophic factors and other agents to preserve the phenotype and promote the survival of adult motor neurons in vivo. PMID- 8207128 TI - Age and damage induced changes in amyloid protein precursor immunohistochemistry in the rat brain. AB - Alzheimer's disease (AD) is characterized by the extensive deposition of the 42 amino-acid beta-amyloid or A4 protein in neuritic plaques and neurofibrillary tangles within the brain. This protein is liberated from the much larger amyloid protein precursor (APP). Multiple species of APP have been proposed, including several forms that contain a 56 amino acid insert sequence analogous to the Kunitz protease inhibitors. Although expression of APP mRNA is reportedly altered in AD brain and various roles for APP have been proposed, the pathogenesis of amyloid deposition and AD remains unclear. AD is also characterized by specific memory impairments associated with decreased cholinergic activity. While aging rats do not develop mature amyloid pathology, behaviorally impaired aged rats demonstrate an analogous cholinergic decline. In this study, we examined behaviorally characterized aged rats and normal young controls for changes in APP immunohistochemistry by using anti-APP antibodies, which detect N- or C-terminal regions and which distinguish APP species with or without the Kunitz protease inhibitor domain. The results show specific age- and behavior-related changes in cortical APP immunoreactivity as well as limited numbers of APP immunoreactive deposits in the aged rats. Additionally, we found that lesions of the fimbria fornix pathway, which in part mimic the memory impairments and loss of cholinergic activity seen in AD, result in the marked accumulation of APP immunoreactive material in the region of cholinergic fiber degeneration in the hippocampus. These findings are discussed in relation to the pathogenesis of AD in humans. PMID- 8207129 TI - Differential distribution of amyloid protein precursor immunoreactivity in the rat brain studied by using five different antibodies. AB - The beta-amyloid or A4 protein is found deposited in neuritic plaques and neurofibrillary tangles in Alzheimer's disease (AD) affected brains and in the brains of adults with Down's Syndrome. The precursor to this 42 amino acid protein is the 695 amino acid long amyloid protein precursor (APP-695). Two additional APP species, APP-751 and APP-770, each contain a 56-amino-acid insert sequence that is analogous to Kunitz protease inhibitors. APP mRNA is widely distributed in both the human and rat brain, although the adult rat does not develop mature amyloid pathology. In this study we used antibodies against the N terminus, junction site (unique to APP-695) insert sequence (unique to APP-751, 770), A4 region, and C-terminus of APP to immunolabel sections from throughout the young adult rat brain. From these results we constructed maps of the staining pattern of each antibody. We found that APP is widely distributed throughout the brain, that labelling is predominantly neuronal in character, and that there is marked variation among the antibodies in the extent of labelling, the particular cell populations stained, and the structures labelled within individual cells. The differential staining patterns observed with the five different antibodies suggest that the way APP is processed differs from one region to another and within different compartments in the cell. The specificity of the antibodies was established by Western blot analysis, in which APP species of approximately 95 and 110 kD were found. Our findings on the distribution of APP provide a foundation for further investigations into the normal role of APP and the pathogenesis of AD. PMID- 8207130 TI - Topographical distribution of reduced nicotinamide adenine dinucleotide phosphate diaphorase in the brain of the Japanese quail. AB - The distribution of reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity was histochemically investigated in the Japanese quail brain. This enzyme is now considered responsible for the synthesis of nitric oxide, a novel neural messenger whose distribution has not been described in the avian brain until now. The histochemical technique provides a simple and reliable method for staining selected populations of neurons throughout the avian brain. In the telencephalon several regions showed heavily stained NADPH-diaphorase positive neurons and processes. In particular the paleostriatal-paraolfactory lobe complex showed the greatest presence of both positive cells and processes. Neurons and processes were also observed in several regions of the hyperstriatum as well as in the archistriatal nucleus taeniae. Some regions, such as the ectostriatum and the hippocampus, had no positive elements. In the diencephalon, the magnocellular hypothalamic system, which in mammals shows NADPH-diaphorase activity, did not show any particular accumulation of reaction product. On the contrary, retinorecipient areas, such as the visual suprachiasmatic nucleus and the lateral geniculate complex, displayed a composite structure of both positive neurons and processes. The brainstem revealed a large NADPH-diaphorase positive population extending through the tegmental nuclei to the locus coeruleus and subcoeruleus. A complex organization was also observed in the optic lobe, where fusiform elements were distributed within the stratum griseum and superficialis of the tectum. In the medulla, a dense terminal field was observed at the level of the nucleus of the solitary tract, whereas scattered neurons were located within the reticular nuclei. Although the staining of neurons and tracts was highly selective, the positive cells did not correspond to any single known neurotransmitter, neuropeptide, or neuroactive molecule system. Several sensory pathways were heavily stained for the NADPH-diaphorase, including part of the olfactory, visual, and auditory pathways. The findings of the present study reveal that the NADPH-diaphorase-containing systems in the avian brain are organized according to a pattern comparable, because of its complexity, to that observed in mammals. However, important interspecific differences suggest that this novel neural system might be involved in diverse tasks. PMID- 8207131 TI - New data on the short-term effects of tone exposure. AB - Three experiments studied the short-term effects of moderate- and high-level tone exposures on threshold and loudness. Experiment 1 measured temporary threshold and loudness shifts (TTS and TLS) due to a 1000-Hz exposure at a moderate level (65 dB SPL) as a function of exposure duration. Whereas there was no significant TTS, TLS was as high as 11 dB and recovered rapidly. TLS was significantly larger for the highest test levels. TTS and TLS were practically independent of exposure duration. Experiment 2 measured TTS and TLS as a function of test frequency following exposures to 500-, 1000-, or 3000-Hz tones at 65 dB SPL. The frequency patterns of TLS were established at test levels of 20-60 phons. TLS and TTS had similar frequency patterns with a maximum at the exposure frequency, but TLS patterns were higher and more extended than those of TTS. In experiment 3, subjects were exposed to a 1000-Hz tone at a high level (90 dB SPL). Frequency patterns for TTS or TLS at a 60-dB test level were measured repeatedly during 5 1/2 min after the end of exposure. Two short-term effects were observed immediately after the exposure: (1) a slight TTS (4.5 dB) at the exposure frequency which disappeared 2 to 3 min later; and (2) a large TLS (9 dB) which extended over the whole range of test frequencies, recovered rapidly, and had disappeared by 330 s after exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207132 TI - The critical modulation frequency and its relationship to auditory filtering at low frequencies. AB - If the thresholds for detecting sinusoidal amplitude or frequency modulation of a sinusoidal carrier with frequency fc are expressed in terms of the respective modulation indices, m and beta, the ratio beta/m decreases as the modulation frequency increases, and approaches an asymptotic value of unity. The modulation frequency at which the ratio first becomes unity is called the critical modulation frequency (CMF). It has been suggested that the CMF is reached when the spectral sidebands in the stimulus first become detectable and that the CMF corresponds to half the value of the critical bandwidth (CB) at fc. In this paper it is demonstrated that the CMF is confounded as a measure of frequency selectivity at low frequencies, since, for modulation frequencies around the CMF, the sideband that is most detectable changes with fc. For values of fc above 250 Hz, the lower sideband is most detectable. For values of fc below 200 Hz, the upper sideband is most detectable. These findings can account for the fact that the CMF flattens off at low carrier frequencies, reaching an asymptotic value of about 40 Hz, whereas the auditory filter bandwidth continues to decrease down to very low center frequencies. PMID- 8207133 TI - Intensity discrimination and increment detection at 16 kHz. AB - When presented for several seconds, a very high-frequency tone can decay to inaudibility in subjects with normal hearing. The purpose of the present study was to determine how such a tone behaves once it is inaudible. Intensity difference limens (DLs) at 16 kHz were measured for gated (audible) and continuous (inaudible) pedestals over a range of pedestal sensation levels from about 0-60 dB, and were compared with those obtained in the same two subjects at 1 kHz [N. F. Viemeister and S. P. Bacon, J. Acoust, Soc. Am. 84, 172-178 (1988)]. The results at the two frequencies were remarkably similar, indicating, among other things, that a continuous 16-kHz pedestal--despite being inaudible-behaves as if it were audible. In addition, the results suggest that there is little or no relationship between high-frequency tone decay and intensity DLs. The locus of this long-term adaptation effect is presumably peripheral to the site where binaural interactions occur, and may be at the hair cell or auditory nerve. The intensity DLs are more consistent with a multiplicative model of (long-term) adaptation than with a subtractive model, suggesting that the nature of this adaptation is different from that which characterizes short-term adaptation. PMID- 8207134 TI - Detecting mistuning in the presence of synchronous and asynchronous interfering sounds. AB - Listeners were presented with the first seven harmonics of a 500-Hz fundamental (the "test complex"), and were required to detect a mistuning imposed on its fourth harmonic (the "target"), which had a nominal frequency of 2000 Hz. All components were frequency modulated by a 5-Hz sinusoid, and, in the signal interval of each 2IFC trial, a 180 degrees phase delay was imposed on the modulation applied to the target. This led to a mistuning proportional to the depth of FM, which was varied adaptively to obtain thresholds. When an unmodulated 2000-Hz "interfering" sinusoid was gated on and off together with the test complex, thresholds were largely unaffected, provided the level of the interfere was more than 3 dB below that of the target. However, when the interferer started before and ended after the test complex there was a substantial elevation in threshold, even at low interfere levels. The elevation was mainly due to the portion of the interferer preceding the test complex, but the part following the complex also had some effect. When the offset asynchrony between the interferer and the test complex was held constant at 100 ms and the onset asynchrony varied, the highest thresholds occurred at an onset asynchrony of 200 ms. A threshold elevation could also be achieved by replacing the interferer with a narrow-band noise centered on 2000 Hz, or by preceding the test complex with an interferer consisting of all components except 2000 Hz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207135 TI - Effects of frequency and amplitude modulation on the pitch of a complex tone with a mistuned harmonic. AB - It has previously been found that when a single low-numbered harmonic of a complex tone is progressively mistuned, for mistunings up to about 3%, the pitch of the complex changes in the direction of the mistuning but for larger mistunings (by about 8%) the pitch returns to its original value. This result is compatible with the operation of a mechanism such as a graded harmonic sieve, which can reject from the calculation of pitch those frequency components that are implausibly distant from a harmonic frequency. The first experiment shows that the tolerance of such a sieve is increased when all the components of the complex tone (including the mistuned component) share a common pattern of frequency modulation at a rate of 6 Hz. The second experiment shows that the tolerance of the sieve is not increased when the components share a common pattern of amplitude modulation at 17 Hz. The third experiment replicates these findings and further shows that the increase in sieve tolerance for FM, but not for AM, occurs at both 6 and at 17 Hz. PMID- 8207137 TI - Detection and recognition of repeated tones and tonal patterns. AB - This study examined the effect of multiple presentations on signal detection and on signal recognition (identifying one signal from a set of four possible signals) for three different sets of signals. One set was four sinusoids (100-ms duration, frequencies of 707, 1000, 1414, and 2000 Hz). Two sets contained tonal patterns each made of a sequence of seven, 100-ms, sinusoidal components. In the first set, the four patterns consisted of the same seven sinusoids in different orders. In the second set, the four patterns had the same order of relative frequencies, but had frequencies from different 1/4 oct bands centered at 707, 1000, 1414, and 2000 Hz. All stimuli were adjusted to be equally detectable in the presence of a continuous white noise (eta 0 = 20 dB SPL). Each trial contained 1, 2, 4, 8, or 16 presentations of a given signal plus noise (probability of a signal was 0.5) or noise alone. Detectability of the sinusoids generally increased as the square root of the number of presentations; detectability for the tonal patterns increased at a slower rate. Recognition was generally poorer than predicted by the recognition theorem [S.J. Starr, C. E. Metz, L.B. Lusted, and D.J. Goodenough, Radiology 116, 533-538 (1975)] and increased with multiple presentations only as much as expected from the increase in signal detectability. PMID- 8207136 TI - Monotic and dichotic modulation detection interference in practiced and unpracticed subjects. AB - The threshold for detecting 10-Hz amplitude modulation of a 1-kHz carrier was measured in quiet and in the presence of a 4-kHz masker carrier that was either unmodulated or amplitude modulated at a depth of 1.0 and at rates from 2 to 80 Hz. The signal and masker were presented to the same ear (monotic condition) or to opposite ears (dichotic condition), and the subjects either had no previous experience with psychoacoustic experiments (n = 10) or had from 16 to about 70 h of experience with modulation-detection tasks (n = 4). There were no significant differences between the two groups of subjects, although there was a significant effect of presentation mode. Thresholds generally were higher in the monotic condition, particularly when the masker rate was similar to the signal rate. According to excitation-pattern analyses, the greater interference in the monotic condition is unlikely due to peripheral interactions. PMID- 8207138 TI - The effect of conductive hearing loss on the masking-level difference: insert versus standard earphones. AB - Previous studies have indicated that the masking-level difference is reduced in listeners having conductive hearing loss, even when sensation level is controlled. According to the crosstalk hypothesis, this deficit can be explained in terms of reduced binaural cues at the level of the cochleas, due to acoustic contributions from the bone conduction route. It is possible that such a deficit can be overcome through the use of insert earphones, because such transducers provide a high degree of interaural attenuation. In this study, NoSo and NoS tau thresholds were measured in normal-hearing subjects and in subjects having hearing loss due to otosclerosis, using both standard TDH earphones encased in NAF-48490-1 circumaural cushions and deeply seated Etymotic 3A insert earphones. Masking noise was presented both at a fixed sound-pressure level and at a fixed sensation level. The results did not indicate consistently larger MLDs with insert earphones for either group of subjects, for either type of presentation level. The MLDs of the hearing-impaired subjects often remained abnormally small even when the insert transducers were used and the noise was presented at a fixed SL. Whereas acoustic crosstalk appeared to have a role in the results obtained, other factors (perhaps related to long-term hearing threshold asymmetry and/or interaural phase mismatch) also were apparently involved. PMID- 8207139 TI - Pitch perception for different modes of stimulation using the cochlear multiple electrode prosthesis. AB - Numerical estimations of pitch were obtained from nine postlinguistically deafened adults using the 22-electrode cochlear implant manufactured by Cochlear Pty. Limited. A series of electrodes on the array were stimulated using three modes of stimulation: Bipolar (BP), common ground (CG), and monopolar (MONO). In BP stimulation, an electric current was passed between two electrodes separated by one electrode for eight patients and two electrodes for one patient. In CG stimulation, a single electrode was activated and the other electrodes on the array were connected together to serve as the return path for the current. In MONO stimulation, an electric current was passed between a single electrode and the most basal electrode on the array. Pitch estimations were generally consistent with the tonotopic organization of the cochlea. There was a marked reversal in pitch for electrodes in the middle of the array using CG stimulation for three patients. A reduced range of pitch using MONO stimulation was recorded for patients where the most basal electrode was internal to the cochlea. There were also individual differences in pitch estimations between the three modes of stimulation for most patients. The current levels required to elicit threshold (T) and comfortable listening (C) levels were, in general, higher for BP stimulation than for CG stimulation and were lowest for MONO stimulation. For CG stimulation, there was a tendency for T and C levels to be higher for electrodes in the middle of the array than at the basal or apical ends. For MONO stimulation, T and C levels uniformly increased in an apical to basal direction for the majority of patients. There was no consistent pattern in T and C levels for BP stimulation. The size of the range of usable hearing using CG stimulation tended to be similar to that using BP stimulation and was usually higher than that using MONO stimulation. PMID- 8207140 TI - Effect of reducing slow temporal modulations on speech reception. AB - The effect of reducing low-frequency modulations in the temporal envelope on the speech-reception threshold (SRT) for sentences in noise and on phoneme identification was investigated. For this purpose, speech was split up into a series of frequency bands (1/4, 1/2, or 1 oct wide) and the amplitude envelope for each band was high-pass filtered at cutoff frequencies of 1, 2, 4, 8, 16, 32, 64, or 128 Hz, or infinity (completely flattened). Results for 42 normal-hearing listeners show: (1) A clear reduction in sentence intelligibility with narrow band processing for cutoff frequencies above 64 Hz; and (2) no reduction of sentence intelligibility when only amplitude variations below 4 Hz are reduced. Based on the modulation transfer function of some conditions, it is concluded that fast multichannel dynamic compression leads to an insignificant change in masked SRT. Combining these results with previous data on low-pass envelope filtering (temporal smearing) [Drullman et al., J. Acoust. Soc. Am. 95, 1053-1064 (1994)] shows that at 8-10 Hz the temporal modulation spectrum is divided into two equally important parts. Vowel and consonant identification with nonsense syllables were studied for cutoff frequencies of 2, 8, 32, 128 Hz, and infinity, processed in 1/4-oct bands. Results for 12 subjects indicate that, just as for low-pass envelope filtering, consonants are more affected than vowels. Errors in vowel identification mainly consist of reduced recognition of diphthongs and of durational confusions. For the consonants there are no clear confusion patterns, but stops appear to suffer least. In most cases, the responses tend to fall into the correct category (stop, fricative, or vowel-like). PMID- 8207141 TI - Cues for perception of the diphthong /aI/ in either noise or reverberation. Part I. Duration of the transition. AB - Location of boundaries (the 50% response point) and slopes of identification functions were determined for synthesized /a-aI/ vowel continua. Within each continuum, the stimuli contained a steady-state segment followed by a transition in which the frequencies of formants changed in time. Here, F1 changed in a downward direction and F2 changed in an upward direction. Total duration of each stimulus was 200 ms. The duration of the transition was increased in steps from 0 to 140 ms. Two patterns of formant transition were used: (1) formants changing in the direction of, but not reaching, target frequencies (except in the end-point stimulus), and (2) formants reaching F1 and F2 targets. The data were collected with ten normal-hearing and ten hearing-impaired subjects. The boundaries and slopes were determined for four listening conditions: quiet, noise, short reverberation (0.8 s), and long reverberation (1.1 s). The location of boundaries depended upon: (1) pattern of formant transitions, (2) listening condition, and (3) status of subjects' hearing. Generally, longer transitions were needed for formants changing in the direction of, but not reaching, target frequencies, than for those reaching F1 and F2 targets. The required transition durations were similar in quiet and noise, but were longer in reverberation. The hearing impaired subjects generally required longer transitions to reach the boundaries than normal-hearing subjects. The slopes of the identification functions were shallower in either noise or reverberation than in quiet and were shallower for hearing-impaired than for normal-hearing subjects. In reverberation, the slopes for formants reaching targets were shallower than the slopes for stimuli with formants changing in the direction of target frequencies. The relationships between these findings and identification errors for naturally produced tokens of the diphthong /aI/ are discussed. PMID- 8207143 TI - Neural processing of musical timbre by musicians, nonmusicians, and musicians possessing absolute pitch. AB - Cognitive event-related potentials (ERPs) were measured during a timbre discrimination task from three subject groups varying in musical experience. The P3 component of the ERP was recorded from musicians with absolute pitch, musicians without absolute pitch, and nonmusicians during a task comprising timbres of varying difficulty. The three-timbre series, all of which consisted of the same pitch, were (1) string instruments in the same family (cello and viola), (2) flutes made of different materials (silver and wood), and (3) instruments of slightly different size (B-flat versus F tubas). The amplitude and latency of the P3 component varied systematically as a function of musical experience and type of timbre discrimination. The difficult timbre task resulted in mean P3 amplitudes which were larger for musicians relative to nonmusicians, however P3 amplitudes were similar for the two additional timbre series. The mean P3 latencies for musicians were shorter when compared to nonmusicians across all three series. In comparison, the AP subjects displayed the shortest mean P3 latencies, but had smaller P3 amplitudes relative to both musicians and nonmusicians. The implications of these findings suggest that perceptual tasks involving one of the fundamental building blocks of music, namely timbre, does elicit differential brain activity from memory or information processing systems from subjects with varying degrees of musical training. PMID- 8207144 TI - Comparison of sonar discrimination: dolphin and an artificial neural network. AB - The capability of an echolocating dolphin to discriminate differences in the wall thickness of cylinders (3.81 cm o.d. and 12.7 cm length) was determined by Au and Pawloski [J. Comp. Physiol. A 170, 41-47 (1992)]. The dolphin was required to discriminate a standard target from comparison targets of differing wall thicknesses. Performance varied from 96% to 56% correct depending on the wall thickness of the comparison targets. The 75% correct threshold was determined to be wall thickness differences of -0.23 mm for comparison targets with thinner walls and +0.27 mm for comparison targets with thicker walls than the standard. The dolphin performance was unchanged in the presence of artificial broadband masking noise until the echo-energy-to-noise ratio fell below approximately 15 dB. A counterpropagation artificial neural network was used to examine broadband echo features from the same cylinders. Features of the echoes were determined by passing them through a filter bank of constant-Q filters. Echo features of the standard and each comparison target were analyzed in pairs by a neural network having two output nodes. Twenty echoes per target were used in the training set and 30 additional echoes per target were used in the test set. For the noise free condition, the network performed at a comparable level to the dolphin for Q values between 4 and 5. In the presence of noise, Q values between 7 and 8 were needed before the network could perform at a comparable level to the dolphin for echo-energy-to-noise ratios of 10 and 15 dB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207142 TI - The influence of sentential speaking rate on the internal structure of phonetic categories. AB - In the experiments reported in this paper we compared the effects of syllable level and sentence-level speaking rate on phonetic perception. In an earlier set of experiments, we found that syllable-level rate influences the internal perceptual structure of phonetic categories [Miller and Volaitis, Percept. Psychophys. 46, 505-512 (1989); Volaitis and Miller, J. Acoust. Soc. Am. 92, 723 735 (1992)]. Specifically, a change in target-syllable rate altered the location of the stimuli judged to be the best category exemplars, as well as the width of this best-exemplar range. In the present investigation, it was asked whether sentence-level rate has the same influence. It was found that slowing sentence rate shifted the location of the best-exemplar range, but did not alter its width. These findings are discussed in terms of timing mechanisms that may operate during speech perception. PMID- 8207145 TI - Stroboscopic hearing as a mechanism for prey discrimination in frequency modulated bats? AB - A hypothesis was proposed that bats employing frequency-modulated (FM) echolocation pulses could utilize dynamic information of a flying insect to discriminate prey on the basis of "stroboscopic hearing." To test this hypothesis, single unit recordings were made from the inferior colliculus (IC) of the little brown bat, Myotis lucifugus. Response characteristics of IC units to trains of modulated and unmodulated sound pulses were analyzed at various pulse repetition rates that corresponded to a bat's pulse emission rates during the different stages of its target directed flight. The results show that amplitude modulation (AM) across a train of sound pulses was faithfully encoded in the units' discharge pattern when the pulse repetition rate was different from the AM frequency. When the AM frequency was integer multiples of the pulse repetition rate, the stimulus amplitude was reduced drastically under these conditions. Consequently, the discharge of an IC unit diminished precipitously, or if there was a phase delay between the pulse onset and the modulating sinusoidal waveform the unit fired to each modulation cycle with more or less the same vigor as if the modulation was absent. These data indicate that the across-pulse amplitude modulation becomes undetectable when the AM frequency is integer multiples of the pulse repetition rate. It is interpreted that FM bats can potentially employ a "stroboscopic hearing" strategy for discriminating insects on the basis of the wing-beat frequency of the prey. PMID- 8207146 TI - Acoustic information available to bats using frequency-modulated sounds for the perception of insect prey. AB - Through the present study, the acoustic information available to an echolocating bat that uses brief frequency-modulated (FM) sonar sounds for the pursuit and capture of insect prey has been characterized. Computer-generated sonar pulses were broadcast at tethered insects, and the returning echoes were recorded on analog tape at high speed for off-line analyses. Echoes from stationary and fluttering insects were displayed using time waveform, spectrogram, power spectrum, and cross-correlation representations. The results show echo signatures for the different insect species studied, which change with the angle of incident sound. Sequences of echoes from fluttering insects show irregular changes in sound amplitude and time-frequency structure, reflecting a random temporal relation between the changing wing position and the arrival of incident sound. A set of recordings that controlled the temporal relation between incident sound and insect wing position suggests that information about the spatial profile of a flying insect could be enhanced if the bat were to produce a sequence of sounds that synchronized briefly with the moving target's wing-beat cycle. From this study, it has been proposed that the FM bat receives stroboscopic-like glimpses of fluttering prey whose spatial representation depends on the operation of the bat's sonar receiver. PMID- 8207147 TI - Equestrian injuries: a five-year review. AB - A retrospective chart review was conducted to define the demographic and injury patterns of patients presenting to the emergency department (ED). The setting is a rural/small urban tertiary care center with approximately 40,000 visits per year. All patients presenting to the ED from January 1986 through December 1990 with equestrian-related injuries were enrolled in the study. Measurements included age, sex, mechanism of injury, injury or injuries diagnosed, admission to the hospital, morbidity, and mortality. A total of 142 patients met the inclusion criteria. The majority of injuries occurred when the patient fell from a horse. There were also a large number of injuries associated with handling the horse. Most injuries were minor, but 15% required hospital admission. There were no deaths. In conclusion, equestrian activities are associated with a risk of serious injury to both riders and handlers of horses. Education of both the public and primary care physicians should focus on injury prevention. PMID- 8207148 TI - Arterial gas embolism and hemoconcentration. AB - The charts of all patients with diving-related accidents presenting between 1983 and 1991 were reviewed. Individuals who sustained a neurologic deficit attributable to occlusion of part of the cerebral circulation within 10 minutes of surfacing from a dive and who had a depth time profile less than 80% of the U.S. Navy "no-stop" limits were considered to have had an arterial gas embolism. Their records were reviewed to determine the hematocrit upon first presentation and the final hematocrit prior to discharge or death. Twenty-three patients had hematocrit determinations on more than one occasion. There was a significant decrease from initial to final hematocrit for these patients. No source of significant blood loss was identified in any patient. A significant correlation was found between the magnitude of the fall in hematocrit and the eventual neurologic outcome. We conclude that gas embolism diagnosed using the above criteria produces hemoconcentration, and the degree of hemoconcentration correlates with the severity of the gas embolism. These observations suggest that the pathophysiology of gas embolism is more complex than previously thought and must include diffuse endothelial injury resulting in leak of fluid from the intravascular space. PMID- 8207149 TI - Tension hydrothorax: a rare complication of continuous cyclical peritoneal dialysis. AB - Continuous cyclical peritoneal dialysis (CCPD) is a well-established, effective method of maintenance dialysis in patients with end-stage renal disease (ESRD). Massive hydrothorax producing hemodynamic compromise (tension hydrothorax) has been documented as an infrequent complication of both acute temporary peritoneal dialysis and continuous ambulatory peritoneal dialysis (CAPD). We recently saw a patient with massive hydrothorax as a consequence of CCPD. The etiology of this rare condition is thought to be that of a diaphragmatic defect with a one-way valve mechanism. Diagnosis is made by aspiration of the pleural fluid and estimation of pleural fluid glucose. Management of these patients requires pleural drainage and changing to hemodialysis if possible. PMID- 8207150 TI - A serious skin sulfur mustard burn from an artillery shell. AB - Despite the Geneva Protocol of 1925 and the Paris Conference on Prohibition of Chemical Weapons in 1989, sulfur mustard and other chemical weapons continue to pose a hazard to both civilians and soldiers. The presence of artillery shells containing sulfur mustard, both in waters where these shells were dumped and in old battlefields, presents a problem in times of peace, especially for those who collect wartime memorabilia. Past literature has reported several hundred incidents involving fishermen who inadvertently pulled leaking shells aboard their fishing vessels, thereby exposing themselves to the vesicant chemical. Other literature reports exposure to children who found the chemical shells in old battlefields. The purpose of this article is to report the first case of a serious sulfur mustard burn that occurred after removing the detonator from an old artillery shell in a historic battle field near Verdun, France. The circumstances surrounding the injury, the diagnosis and management of injuries secondary to sulfur mustard, and the long-term consequences to the patient are presented and discussed. Although skin grafting has been used in the management of other chemical burn injuries, this report is the first to describe the need for split-thickness skin grafts in the management of a patient with sulfur mustard burns. PMID- 8207151 TI - An unusual presentation of Fitz-Hugh-Curtis syndrome. AB - A case of Fitz-Hugh-Curtis syndrome masquerading as a perforated peptic ulcer is presented. The pathophysiology, clinical presentation, differential diagnosis, and management of this syndrome are discussed. PMID- 8207152 TI - Colchicine poisoning. AB - Colchicine poisoning is an unusual but serious form of drug intoxication. Although relatively uncommon, colchicine poisoning may produce life-threatening systemic effects that must be recognized and treated by the emergency physician. This alkaloid found in Colchicum autumnale is used primarily in the treatment of gout. In toxic doses it produces nausea and vomiting, and bone marrow suppression often leading to sepsis, hypocalcemia, adult respiratory distress syndrome, and direct cardiotoxic effects. Treatment requires early recognition and supportive care including fluid and electrolyte replacement and occasionally blood component replacement therapy. Recent experiments using colchicine-specific antibodies have demonstrated beneficial effects on colchicine intoxication. PMID- 8207153 TI - Recurrent digoxin overdose and treatment with digoxin-specific Fab antibody fragments. AB - A case of overdose with digoxin on three separate occasions is presented. The patient received digoxin-specific Fab antibody fragments on each presentation without adverse effects. A discussion of digoxin toxicity and specific treatment follows. Immunologic aspects of therapy are emphasized. PMID- 8207154 TI - Code blue: what's new? AB - In October 1992, lengthy new guidelines for cardiopulmonary resuscitation and emergency cardiac care were published by the Emergency Cardiac Care Committee and Subcommittees of the American Heart Association. These guidelines represent the efforts of the world's experts in emergency cardiac care. Yet they may be difficult for the busy clinician to digest in a timely fashion. In this article we summarize the changes in the guidelines from the 1986 version. It is not intended as a substitute for the original document but rather as an adjunct to help the clinician assimilate this new information. PMID- 8207155 TI - Survival with acute primary coronary artery dissection: a case report and review of the literature. AB - Primary coronary artery dissection is a rare etiology of acute myocardial infarction (AMI) that often has devastating consequences. We present the case of a 46-year-old male survivor of primary coronary artery dissection who was diagnosed angiographically. He suffered a non-Q-wave MI but had no electrocardiographic (ECG) changes during his course. A review of the literature of primary coronary artery dissection, particularly those diagnosed antemortem, is provided. PMID- 8207156 TI - "Abnormal" electrocardiograms in patients with cocaine-associated chest pain are due to "normal" variants. AB - "Abnormal" electrocardiograms are found in 56% to 84% of patients with cocaine associated chest pain. This study was designed to assess whether these findings can be explained by "normal" variations in young patients' electrocardiograms. This cross-sectional study was conducted in a municipal hospital emergency department and walk-in clinic. History and results of an electrocardiogram for consecutive patients with cocaine-associated chest pain, aged 18 to 35 years, were compared to normal controls matched for age, race, and gender. Electrocardiograms underwent detailed analysis by two physicians blinded to both the study protocol and the hypothesis. Interphysician concordance for electrocardiographic diagnosis was substantial. There were 112 patients enrolled, 56 in each group. There was no significant difference found in the mean frequency of electrocardiographic diagnoses between the cocaine-associated chest pain patients and controls. The early repolarization variant was common. In conclusion, "normal" variations (J point and ST segment elevations) account for many of the "abnormal" electrocardiograms observed in young patients with cocaine associated chest pain. Further study is needed to define the prevalence of these "normal" variations, and to determine if standard electrocardiographic criteria for thrombolysis apply to young patients. PMID- 8207157 TI - The accuracy of ST segment deviation in prehospital cardiac monitoring. AB - Elevation or depression of the ST segment of the 12-lead electrocardiogram is an important and established marker of myocardial ischemia or injury. The ST segment deviation in normal individuals using standard cardiac monitoring equipment in the clinical setting of prehospital transport has not been studied. The hypothesis that we tested is that ST segment changes do not occur in normal subjects on standard prehospital cardiac monitors during transport. During a simulated transport, we monitored healthy volunteers of both sexes between the ages of 20 and 30 who had a normal cardiovascular history, physical examination, and 12-lead electrocardiogram. Fourteen of 34 subjects (41%) who qualified as normal exhibited ST segment deviation on the monitor. Of these 14, 11 exhibited ST segment depression, and 3 exhibited ST segment elevation. We conclude that normal individuals can exhibit ST segment deviation on standard prehospital cardiac monitoring equipment during routine transport. PMID- 8207158 TI - Acute epiglottitis in a rural area: experiences with an anesthesiologist-staffed ambulance helicopter. AB - The majority of fatalities due to acute epiglottitis (AE) result from prehospital airway problems. We reviewed the courses of 14 patients with AE treated by an aeromedical team consisting of an anesthesiologist and a paramedic. Eight patients were transported from a physician's office or from the patient's own home. One patient was intubated at the scene, and two received ventilatory support with mask and bag en route to the hospital. Two patients suffered cardiopulmonary arrest before arrival of the aeromedical team, both resulting in severe hypoxic encephalopathy. All six patients transported from hospitals were intubated prior to the helicopter transport. Based on our own experience and a review of the literature, we discuss prehospital airway management in this group of patients. PMID- 8207159 TI - Intubation techniques in the helicopter. AB - The purpose of this study is an analysis of 630 field intubations of trauma patients by flight personnel of the San Diego Life Flight program. We compared nasotracheal intubation to rapid sequence induction orotracheal intubation and noninduced orotracheal intubation. We measured success of intubation route, complications, and overall patient outcome. Flight records, quality assurance flight procedure data, and hospitalization data from the San Diego Trauma Registry were reviewed over a 4-year period, from 1988 to 1991. The results of our study show that rapid sequence induction orotracheal intubation has a higher success rate, fewer complications, and a better patient outcome compared to noninduced orotracheal intubation and blind nasotracheal intubation. We recommend that rapid sequence induction oral intubation be the standard method for prehospital airway management in trauma patients. PMID- 8207160 TI - Radiographic diagnosis of quadriceps tendon rupture: analysis of diagnostic failure. AB - In a multi-institution study, 18 knees with complete quadriceps tendon ruptures (QTRs) were reviewed to analyze the cause of failure in radiographic diagnosis. Only 6 of the 18 knees were diagnosed correctly initially. This occurred even though almost all knee radiographs showed more than three abnormalities compatible with QTR (obliteration of quadriceps tendon, suprapatellar mass, suprapatellar calcific density, or patella baja). Of the 12 diagnostic failures, only 3 were considered to be complete failure. Nine primary reports (50%) were classified as incomplete diagnosis and could be correctly diagnosed if the attention of radiologists was focused to the quadriceps mechanism. We conclude that better understanding of radiographic abnormalities in QTR is necessary for the improvement of primary radiological diagnosis. PMID- 8207161 TI - Hands across the gap: a novel strategy. PMID- 8207162 TI - Pitfalls in the administration of digoxin-specific Fab fragments. PMID- 8207163 TI - Airway management, penetrating neck trauma. PMID- 8207164 TI - Objectives to direct the training of emergency medicine residents on off-service rotations: internal medicine III. AB - Internal medicine is an essential but diverse field. This is the third in a three part set of objectives for an off-service rotation in general internal medicine for emergency medicine residents. This series may be used to guide the resident during the rotation or to serve as part of a teaching program integrated with didactic training and emergency department experience. PMID- 8207165 TI - Wake-up call for living. PMID- 8207166 TI - Emergency medicine educational objectives for the undifferentiated physician. AB - The term undifferentiated physician is applied to those physicians who have not received or are not receiving formal postgraduate training in emergency medicine. Many community and university hospitals offer an "emergency medicine" experience to this group of physicians, but most do not follow a defined curriculum. This set of educational objectives was developed under the auspices of the Canadian Association of Emergency Physicians (CAEP). The objectives are based on an instructional design model known as a Systems Approach Model, which is an objective-based model. The objectives are intended for the undifferentiated physician whose practice will include emergency department (ED) work. The objectives are based on a 2-month rotation in the ED under the supervision of an attending physician who has either College of Family Physicians of Canada or Royal College of Physicians and Surgeons of Canada certification in emergency medicine. The purpose of these objectives is to provide guidelines for a uniform framework for the basic emergency medicine education of these undifferentiated physicians. PMID- 8207167 TI - Pseudoinfection of a total knee arthroplasty. PMID- 8207168 TI - The 'roving team': employee health service in the workplace. PMID- 8207169 TI - Efficacy of pasteurizers. PMID- 8207170 TI - HIV transmission from surgeons and dentists to patients: can models predict the risk? PMID- 8207171 TI - Screening surgeons for HIV infection: assessment of a potential public health program. AB - OBJECTIVE: To develop a model to assess the impact of a program of testing surgeons for human immunodeficiency virus (HIV) on the risk of HIV acquisition by their patients. DESIGN: A Monte Carlo simulation model of physician-to-patient transmission of human immunodeficiency virus (HIV) infection using three different rates of physician-to-patient transmission per percutaneous exposure event (0.15%, 0.3%, 0.6%). Data from the model were developed from a review of the medical literature and from subjective probability estimates when data were not available. We used this model to estimate on a national basis the annual number of cases of HIV transmission from surgeons to patients with and without surgeon testing and practice limitations. RESULTS: The annual number of transmitted cases would range from 0.5 (+/- 0.3), assuming a surgeon HIV prevalence of 0.1% and a surgeon-to-patient transmission rate of 0.15%, to 36.9 (+/- 11.6), assuming a surgeon HIV prevalence of 2% and a surgeon-to-patient transmission rate of 0.6%. After one screening cycle, a mandatory screening program would be expected to reduce the annual transmissions to 0.05 (+/- 0.03) and 3.1 (+/- 1.1), respectively. CONCLUSION: Patients are at low risk of acquiring HIV infection from an infected physician during an invasive procedure. The potential costs of such a program extended beyond the costs of testing and counseling. In communities with high HIV prevalence, screening surgeons and limiting their practices may decrease patient access to care. A disability insurance program also would be required to protect surgeons and trainees performing invasive procedures. Screening surgeons for HIV infection would be a costly undertaking that would reduce but not completely eliminate this risk. PMID- 8207172 TI - Epidemiology of antibiotic use in a neonatal intensive care unit. AB - OBJECTIVE: To determine the incidence and pattern of antibiotic use in a neonatal intensive care unit (NICU). DESIGN: Prospective study of a one-month NICU cohort. Investigators visited each subject, checking nursing notes, antibiotic flow sheets, and laboratory data at each daily visit. SETTING: The NICU at Yale-New Haven Hospital, New Haven, Connecticut; a regional care, level 3 unit in a tertiary care medical center. PATIENTS: All infants admitted to the NICU for one month (n = 63) who resided in the unit for > or = 24 hours. RESULTS: 75% of the infants had antibiotic treatment begun in the first 48 hours of life. The highest rate of antibiotic treatment starts was in premature infants with birthweight less than 1,500 g, 92% of whom received antibiotics in the first 48 hours. In the subsequent days of life the incidence of starting antibiotic treatment was low and sporadic and the prevalence of antibiotic treatment by day of life showed a sharp decline between the third and fourth days of life. Five cross-sectional studies in the nursery showed point-prevalence rates of antibiotic use to be 27% to 43% of the whole NICU population, highest in the intensive care sector of the unit and in those < 72 hours of age. CONCLUSIONS: The high incidence of antibiotic starts in this NICU was largely the result of almost universal treatment of premature infants beginning on the first day of life. The risk of infection in these infants is quite low; more information is needed concerning how to distinguish infants who do not require treatment. This study provides comparison data for NICUs compiling data on incidence and prevalence of antibiotic use and developing programs to limit antibiotic use. PMID- 8207173 TI - Factors affecting mortality outcome and risk of developing nosocomial bloodstream infection. AB - OBJECTIVES: To identify factors associated with developing nosocomial bloodstream infection (NBI) and to identify factors associated with fatal outcome of NBI. DESIGN: Prospective matched and unmatched case-control studies. SETTING: Songklanagarind Hospital, a 640-bed medical school and referral center in Songkla, Thailand. PATIENTS: During a two-year study period, 277 patients of 17,829 total admissions in the hospital services of medicine, surgery, pediatrics, and orthopedics acquired bloodstream infections during hospitalization. For the purpose of identifying factors associated with mortality attributed to NBI, patients who died from NBI were assigned as cases; patients who survived the infections were assigned as controls. For the purpose of identifying risk factors for acquisition of NBI, patients with NBI were considered as cases; patients with the same primary diagnosis as a case but without NBI were eligible to be case-matched controls. RESULTS: Case fatality rate was 37.2% based on deaths attributed specifically to bloodstream infection. Patients who died from NBI, compared with those who survived such infections, were associated with inappropriate antibiotic treatment, infection caused by Klebsiella pneumoniae, and the medicine service. When comparison was made between 239 patients with bloodstream infections and 598 diagnosis-matched controls with no bloodstream infection, infection was found to be associated with old age, number of comorbidities, number of prior infections, neutropenia, duration of immunosuppressive drugs, and duration of indwelling intravenous catheter. CONCLUSION: Awareness of the factors pre-disposing to NBI may permit better surveillance and better care. Although most of the factors associated with development of NBI or death from NBI are not subject to control, some factors are duration of immunosuppressive drugs, duration of indwelling intravenous lines, and choice of antibiotic treatment. PMID- 8207174 TI - A computerized nationwide network for nosocomial infection surveillance in Belgium. AB - OBJECTIVE: To assess the feasibility of computerized nationwide surveillance of nosocomial infections in Belgium, and to obtain preliminary national and hospital specific incidence data. DESIGN: Prospective multicenter cohort study of surgical wound infections (SWI). SETTING: All 218 acute care hospitals in Belgium in the period October 14 to December 14, 1991. RESULTS: Eighty-five of 218 acute care hospitals (39%) succeeded in collecting the required information and in completing this pilot study, although 50% of the participating hospitals had no previous experience in nosocomial infection surveillance. Seventy percent of the small-size hospitals (< 200 beds) did not participate, mainly because of shortages of manpower. A lack of collaboration from clinicians was a problem in most participating hospitals. SWI postdischarge surveillance was most successful when based on information collected by the surgeons at the surgical outpatient clinic; by this method, postdischarge information was obtained on 43.9% of all surgical procedures. A total of 201 infections were observed among 10,537 operations, with a crude incidence rate of 1.91 per 100 operations or 1.51 per 1,000 person-days of observation. Infection rates by operation type and risk indicators are congruent with those of the literature. Survival analysis showed that the overall cumulative infection risk at 21 days postprocedure attained 81.6% of the 30-days risk. CONCLUSION: This nationwide network for nosocomial infection surveillance has introduced the practice of computerized surveillance of performance in a large number of hospitals. Still, several aspects of the surveillance demand to be improved: the collaboration of the clinicians, the quality of the data, and the postdischarge surveillance methodology. PMID- 8207175 TI - Consensus development of quality standards. PMID- 8207177 TI - Quality standard for the treatment of bacteremia. The Infectious Diseases Society of America. AB - OBJECTIVE: The objective of this quality standard is to optimize the treatment of bacteremia in hospitalized patients by ensuring that the antibiotic given is appropriate in terms of the blood culture susceptibility of the pathogen. Although this standard may appear to be minimal in scope, it is needed because appropriate antimicrobial treatment is not given in 5% to 17% of cases. To implement the standard, physicians, pharmacists, and microbiologists will need to devise a coordinated strategy. OPTIONS: We considered criteria for appropriate dosing, most cost-effective selection, proper antibiotic levels in serum, least toxicity, narrowest spectrum, specific clinical indications, and optimal duration of treatment. All these criteria were rejected as the basis for the standard because they were too controversial and too difficult to be applied by a nonphysician chart reviewer. In contrast, the selection of an antibiotic to which the pathogen is sensitive is a noncontroversial criterion and easy for a chart reviewer to apply. OUTCOMES: The standard is designed to reduce the incidence of adverse outcomes of septicemia such as renal failure, prolonged hospitalization, and death. EVIDENCE: Several well-designed clinical trials without randomization as well as case-controlled studies have confirmed the benefit of using an antibiotic that is appropriate in light of the susceptibility of the isolate in blood culture. Prospective, randomized, placebo-controlled trials are not available. VALUES: Our premise is that the presence of bacteremia is a risk factor for serious adverse outcomes. We also believe that the administration of antibiotics must always be guided by the susceptibility report for the pathogen(s) obtained from blood cultures. This concern is more critical for pathogens from the blood than for those from most other body sites. We had evidence that susceptibility reports for pathogens from positive blood cultures were not always used properly. We used group discussion to reach a consensus among the members of the Quality Standards Subcommittee. BENEFITS, HARMS, AND COSTS: Through the implementation of this standard, at least 5% of bacteremias could be treated more appropriately. An unknown number of deaths would likely be prevented, and mortality from bacteremia treated inappropriately would probably be reduced. The primary undesirable feature of the standard is an increased workload of pharmacists and microbiologists. RECOMMENDATIONS: Treatment of bacteremia with an antibiotic that is appropriate in terms of the pathogen's blood-culture susceptibility is a minimal standard of care for all patients. VALIDATION: We consulted more than 50 experts in infectious diseases from the fields of medicine, surgery, pediatrics, obstetrics and gynecology, nursing, epidemiology, pharmacology, and government. In addition, the methods for its implementation were reviewed by the American Society of Hospital Pharmacists and were tested by one of the members of the Quality Standards Subcommittee. SPONSORS: The Quality Standards Subcommittee of the Clinical Affairs Committee of the Infectious Diseases Society of America (IDSA) developed the standard. The subcommittee was composed of representatives of the IDSA (Drs. Gross and McGowan), the Society for Hospital Epidemiology of America (Dr. Wenzel), the Surgical Infection Society (Dr. Dellinger), the Pediatric Infectious Diseases Society (Dr. Krause), the Centers for Disease Control and Prevention (Dr. Martone), the Obstetrics and Gynecology Infectious Diseases Society (Dr. Sweet), and the Association of Practitioners of Infection Control (Ms. Barrett). Funding was provided by the IDSA and the other cooperating organizations. This standard is endorsed by the IDSA. PMID- 8207176 TI - Quality standard for antimicrobial prophylaxis in surgical procedures. The Infectious Diseases Society of America. AB - OBJECTIVE: The objectives of this quality standard are 1) to provide an implementation mechanism that will facilitate the reliable administration of prophylactic antimicrobial agents to patients undergoing operative procedures in which such a practice is judged to be beneficial and 2) to provide a guideline that will help local hospital committees formulate policies and set up mechanisms for their implementation. Although standards in the medical literature spell out recommendations for specific procedures, agents, schedules, and doses, other reports document that these standards frequently are not followed in practice. OPTIONS: We have specified the procedures in which the administration of prophylactic antimicrobial agents has been shown to be beneficial, those in which this practice is widely thought to be beneficial but in which compelling evidence is lacking, and those in which this practice is controversial. We have examined the evidence regarding the optimal timing of drug administration, the optimal dose, and the optimal duration of prophylaxis. OUTCOMES: The intended outcome is more uniform and reliable administration of prophylactic antibiotics in those circumstances where their value has been demonstrated or their use has been judged by the local practicing medical community to be desirable. The result should be a reduction in rates of postoperative wound infection with a limitation on the quantities of antimicrobial agents used in circumstances where they are not likely to help. EVIDENCE: Many prospective, randomized, controlled trials comparing placebo with antibiotic and comparing one antibiotic with another have been conducted. In addition, some trials have compared the efficacy of different doses or methods of administration. Other papers have reported on the apparent efficacy of administration at different times and on actual practice in specific communities. Only a small group of relevant articles found through 1993 are cited herein. When authoritative reviews are available, these--rather than an exhaustive list of original references--are cited. VALUES: We assumed that reducing rates of postoperative infection was valuable but that reducing the total amount of antimicrobial agents employed was also worthwhile. The cost of and morbidity attributable to postoperative wound infections should be weighed against the cost and potential morbidity associated with excessive use of antimicrobial agents. BENEFITS, HARMS, AND COSTS: More reliable administration of antimicrobial agents according to recognized guidelines should prevent some postoperative wound infections while lowering the total quantity of these drugs used. No harms are anticipated. The costs involved are those of the efforts needed on a local basis to design and implement the mechanism that supports uniform and reliable administration of prophylactic antibiotics. RECOMMENDATIONS: All patients for whom prophylactic antimicrobial agents are recommended should receive them. The agents given should be appropriate in light of published guidelines. A short duration of prophylaxis (usually < 24 hours) is recommended. VALIDATION: More than 50 experts in infectious disease and 10 experts in surgical infectious disease and surgical subspecialties reviewed the standard. In addition, the methods for its implementation were reviewed by the American Society of Hospital Pharmacists. SPONSORS: The Quality Standards Subcommittee of the Clinical Affairs Committee of the Infectious Disease Society of America (IDSA) developed the standard. The subcommittee was composed of representatives of the IDSA (Drs. Gross and McGowan), the Society for Hospital Epidemiology of America (Dr. Wenzel), the Surgical Infection Society (Dr. Dellinger), the Pediatric Infectious Disease Society (Dr. Krause), the Centers for Disease Control and Prevention (Dr. Martone), the Obstetrics and Gynecology Infectious Diseases Society (Dr. Sweet), and the Association of Practitioners of Infection Contr PMID- 8207178 TI - Quality standard for assurance of measles immunity among health care workers. The Infectious Diseases Society of America. AB - OBJECTIVE: The objective of this quality standard is to prevent nosocomial transmission of measles by assuring universal measles-mumps-rubella (MMR) vaccination of all health care workers who lack immunity to measles. Although the primary emphasis is on health care workers in hospitals, those at other sites, such as clinics, nursing homes, and schools, are also included. It will be the responsibility of designated individuals at these institutions to implement the standard. OPTIONS: We considered advocating the use of measles vaccine rather than MMR but chose the latter because it also protects against mumps and rubella and because it is more readily available. OUTCOMES: The desired outcome is a reduction in the nosocomial transmission of measles. EVIDENCE: Although direct comparative studies are lacking, nosocomial outbreaks of measles have been reported (as recently as 1992) in institutions where measles immunization of nonimmune health care workers is not universal, whereas such outbreaks have not been reported in institutions with universal immunization. VALUES AND VALIDATION: We consulted more than 50 infectious-disease experts in epidemiology, government, medicine, nursing, obstetrics and gynecology, pediatrics, and surgery. In light of disagreement regarding the implementation of the standard, we used group discussions to reach a consensus. BENEFITS, HARMS, AND COSTS: The consequences of the transmission of measles (and of mumps and rubella) in a health care institution include not only the morbidity and mortality attributable to the disease, but also the significant cost of evaluating and containing an outbreak and the serious disruption of regular hospital routines when control measures are instituted. The potential harm to health care workers after the implementation of the standard consists of untoward effects of MMR vaccine, although the reactions of vaccines should be minimal with adherence to recommended vaccination procedures. Implementation of the standard should entail no expense to health care workers; the precise cost to institutions is unknown, but the expense would be mitigated by prevention of measles outbreaks. RECOMMENDATIONS: We recommend MMR vaccination of all health care workers who lack immunity to measles. SPONSORS: The Quality Standards Subcommittee of the Clinical Affairs Committee of the Infectious Diseases Society of America (IDSA) developed the standard. The subcommittee was composed of representatives of the IDSA (Drs. Gross and McGowan), the Society for Hospital Epidemiology of America (Dr. Wenzel), the Surgical Infection Society (Dr. Dellinger), the Pediatric Infectious Diseases Society (Dr. Krause), the Centers for Disease Control and Prevention (Dr. Martone), the Obstetrics and Gynecology Infectious Diseases Society (Dr. Sweet), and the Association of Practitioners of Infection Control (Ms. Barrett). Funding was provided by the IDSA and the other cooperating organizations. The standard is endorsed by the IDSA. PMID- 8207180 TI - Quality assurance, infection surveillance, and hospital information systems: avoiding the Bermuda Triangle. PMID- 8207179 TI - Infection control in the Russian Federation: review of a tertiary care hospital. PMID- 8207181 TI - HIV testing without consent determined unconstitutional in Alabama. PMID- 8207182 TI - Patient-to-patient transmission of hepatitis B in a dermatology practice. PMID- 8207184 TI - Statistical process control charts. PMID- 8207183 TI - Aspergillosis due to carpet contamination. PMID- 8207185 TI - Iatrogenic hepatitis B infection of three patients in one family. PMID- 8207186 TI - Blunt-tipped suture needles. PMID- 8207187 TI - Antibacterial features of lubraseptic jelly. PMID- 8207188 TI - Yes, Virginia, aseptic technique is very important: maximal barrier precautions during insertion reduce the risk of central venous catheter-related bacteremia. PMID- 8207189 TI - Prevention of central venous catheter-related infections by using maximal sterile barrier precautions during insertion. AB - OBJECTIVE: In many hospitals, the only sterile precautions used during the insertion of a nontunneled central venous catheter are sterile gloves and small sterile drapes. We investigated whether the use of maximal sterile barrier (consisting of mask, cap, sterile gloves, gown, and large drape) would lower the risk of acquiring catheter-related infections. DESIGN: Prospective randomized trial. SETTING: A 500-bed cancer referral center. METHODS: We randomized patients to have their nontunneled central catheter inserted under maximal sterile barrier precautions or control precautions (sterile gloves and small drape only). All patients were followed for 3 months postinsertion or until the catheter was removed, whichever came first. Catheter-related infections were diagnosed by quantitative catheter cultures and/or simultaneous quantitative blood cultures. RESULTS: The 176 patients whose catheters were inserted by using maximal sterile barrier precautions were comparable to the 167 control patients in underlying disease, degree of immuno-suppression, therapeutic interventions, and catheter risk factors for infections (duration and site of catheterization, number of catheter lumen, catheter insertion difficulty, reason for catheter removal). There were a total of four catheter infections in the test group and 12 in the control group (P = 0.03, chi-square test). The catheter-related septicemia rate was 6.3 times higher in the control group (P = 0.06, Fisher's exact test). Most (67%) of the catheter infections in the control group occurred during the first 2 months after insertion, whereas 25% of the catheter infections in the maximal sterile precautions group occurred during the same period (P < 0.01, Fisher's exact test). Cost-benefit analysis showed the use of such precautions to be highly cost-effective. CONCLUSION: Maximal sterile barrier precautions during the insertion of nontunneled catheters reduce the risk of catheter infection. This practice is cost-effective and is consistent with the practice of universal precautions during an invasive procedure. PMID- 8207190 TI - Impact of an educational program for the prevention of colonization of intravascular catheters. AB - OBJECTIVE: To evaluate the efficacy of an educational program for the prevention of catheter colonization. DESIGN: Two cross-sectional studies were carried out in a 500-bed randomly selected area of the hospital, separated by an educational program on the care of intravenous lines based on the Centers for Disease Control and Prevention (CDC) recommendations for the control of catheter-related infections. SETTING: A 2,100-bed urban general hospital affiliated with the University of Madrid (Spain). METHODS: Characteristics of patients and catheters and appropriateness of catheter care were evaluated. Cultures were taken from the point of insertion of the vascular catheter, the hubs, and infusion fluids. When catheter-associated infection was suspected, the distal end of the catheter was sent for culture and two blood cultures were taken. We compared the clinical and microbiological data before and after carrying out an educational program based on CDC recommendations for the control of catheter-related infections. RESULTS: Characteristics of patients and catheters did not differ between the two cross sectional studies. Compared with baseline data, after the educational program we observed a reduction of inappropriate catheter care, from 83% to 38% (45% difference, 95% confidence interval [CI95], 55% to 35%, P < 0.0000), and a reduction in the rate of skin colonization, from 34% to 18% (16% difference, CI95, 26% to 5%, P < 0.001). The frequency of phlebitis (15% versus 14%), hub colonizations (12% versus 11%), catheter colonizations (2% versus 1%), and catheter-related bacteremias (0% versus 0%) remained unchanged between the two cross-sectional studies. CONCLUSIONS: Our educational program improved catheter care and reduced significantly the proportion of skin colonization around the insertion point. However, the educational program did not modify the proportion of hub colonization; because hub colonization has been demonstrated to be a source of line sepsis, our data suggest the need for a specific program directed to the maintenance of catheter hubs. PMID- 8207191 TI - Use of infection control guidelines by workers in healthcare facilities to prevent occupational transmission of HBV and HIV: results from a national survey. AB - OBJECTIVE: Develop national estimates of compliance with infection control guidelines by workers in healthcare facilities to prevent occupational transmission of hepatitis B virus (HBV) and human immunodeficiency virus. DESIGN: A national survey of 3,094 workers in hospitals. SETTINGS: United States ambulatory care hospitals with emergency rooms. RESULTS: While the sampled hospitals had policies that incorporated the Centers for Disease Control and Prevention's (CDC) infection control guidelines, only 55% of patient care staff, 56% of physicians, and 30% of housekeeping staff reported receiving at least one of the shots recommended in the HBV vaccination series. About one half of patient care staff reported that they recapped used needles at least sometimes after giving injections and after drawing blood. Only 43% of patient care staff "always" wore gloves to draw blood. While most patient care staff "always" changed gloves between patients, only 61% reported that they "always" washed their hands after taking off their gloves. One half of patient care staff reported a percutaneous exposure to a patient's blood, and one quarter reported a percutaneous exposure in the past year. The most common cause of these exposures was recapping used needles. CONCLUSIONS: Efforts to reduce exposures to bloodborne pathogens will involve compliance with the Occupational Safety and Health Administration bloodborne pathogens standard and the CDC's infection control guidelines, continued education and training, and emphasis on engineering controls where applicable. PMID- 8207192 TI - Risk factors for central venous catheter-related infections in surgical and intensive care units. The Central Venous Catheter-Related Infections Study Group. AB - OBJECTIVE: To identify avoidable risk factors for central venous catheter (CVC) infections in patients undergoing short-term catheterization. DESIGN: Prospective multicenter cohort study. SETTING: Two university teaching hospitals and five large nonteaching hospitals. PATIENTS: Patients admitted to intensive care units or surgical units and exposed to short-term CVCs. RESULTS: Of 623 catheterization episodes, 9.3% were associated with catheter-related infections (CRI). The skin at the catheter site was frequently colonized (16.2%) and was the potential source of infection in 56.1% of the cases, mostly local infections. The hub was colonized less frequently (3.5%) but was responsible for systemic infections more frequently. The following variables were independently associated with CRI: duration of catheterization (for 7 to 14 days, odds ratio [OR], 3.9; 95% confidence interval [CI]95, 1.4 to 10.7; and for > 14 days, OR, 5.1; CI95, 1.7 to 15.4), coronary care unit service (OR, 6.7; CI95, 1.1 to 42.9) or surgery service (OR, 4.4; CI95, 1.03 to 18.5), second episode of catheterization (OR, 7.6; CI95, 1.8 to 32.3), skin colonization at the insertion site (OR, 56.5; CI95, 10.8 to 296), and hub colonization (OR, 17.9; CI95, 2.4 to 132). The risk associated with skin colonization varied with use of jugular access or simultaneous colonization of the hub. When only symptomatic CRI was considered, the risk associated with hub colonization was consistently higher (OR, 36.6; CI95, 7 to 190) than that associated with skin colonization (OR, 3.2; CI95, 0.7 to 14). Age, transparent dressing, jugular insertion, male gender, duration of catheterization, and hub colonization were independent risk factors for skin colonization. The effect of age varied by type of dressing and vice versa; the effect of jugular access varied by sex; and the effect of transparent dressing varied by length of catheterization and vice versa. Total parenteral nutrition and skin colonization were independently associated with an increased risk of hub colonization. CONCLUSIONS: Skin and hub colonization are the two major determinants for endemic CRIs; colonization of the hub, however, is more frequently associated with more severe infections. In order to reduce CRIs, more efforts should be focused on understanding which factors increase the risk of colonization both of the skin and of the hub. PMID- 8207193 TI - Interim report of the Quality Indicator Study Group. PMID- 8207194 TI - The American Hospital Association. PMID- 8207195 TI - Female-to-female sexual transmission of HIV reported. PMID- 8207196 TI - Immature CD45RA(low)RO(low) T cells in the human cord blood. I. Antecedents of CD45RA+ unprimed T cells. AB - A subset of resting T cells expressing low levels CD45RA and CD45RO molecules (< 1 x 10(3)/cell; CD45RA(low)CD45RO(low)) but high levels of CD45RB and CD38 (5 to 25 x 10(3)/cell) were identified in human cord blood. When these CD45RA(low)RO(low) cells were isolated, they failed to survive in culture (< 10% viability at day 3) unless they were co-cultured on fibroblast monolayers. During the co-culture with fibroblasts, these lymphocytes acquired high levels of cytoplasmic and then membrane CD45RA by day 3 without signs of activation. When stimulated with PHA in the absence of fibroblasts the CD45RA(low)RO(low) cells required monocytes or IL-1 to respond; they rapidly perished if neither were present. On optimal mitogenic stimulation for 48 h in the presence of monocytes, > 90% of CD45RA(low)RO(low) T cells showed only transient CD45RA expression and rapidly acquired CD45RO reactivity. After activation for 48 h the stimulated CD45RA(low)RO(low) subset synthesized high levels of IL-2, comparable to mature peripheral T cells. No IL-4 was detected in these stimulated cultures of cord blood T cells. These data taken together suggest that CD45RA(low)RO(low) T cells in the cord blood are the relatively immature antecedents of CD45RA+RO T cells that require stromal factors for survival in a resting state. The same cells need monocytes or IL-1 for their activation to develop after a short CD45RA+ stage into activated CD45RO+RA(low) T cells with potent IL-2 biosynthetic capacity. An additional study of these cells is warranted to confirm that they are in fact the recent emigrants from the thymus, as suggested by similar observations in animal models. PMID- 8207197 TI - Thiol-mediated redox regulation of lymphocyte proliferation. Possible involvement of adult T cell leukemia-derived factor and glutathione in transferrin receptor expression. AB - The proliferative response of PBMC to PHA, Con A, OKT3 mAb and IL-2-dependent proliferation of PHA-blasts was examined in a thiol-free environment (cultured in a L-cystine- and GSH-free medium). [3H]TdR incorporation assay and cell cycle analysis revealed that stimulated PBMC could not enter the S phase when deprived of these thiol compounds. In thiol-free cultures, an increase in intracellular free Ca2+ concentration and IL-2R alpha-chain/p 55 (Tac) induction was still observed, whereas transferrin receptor induction was markedly reduced, suggesting that the proliferative response of mitogenically stimulated PBMC was arrested in the late G1 phase in which transferrin receptor is induced. In GSH-depleted cultures, a similar reduction of the proliferative response of PBMC and PHA blasts was observed when the concentration of L-cystine was lowered, in a dose dependent manner. Each reduction or loss of proliferative response was partially restored by supplementation of 2-ME or adult T cell leukemia-derived factor (ADF)/human thioredoxin which is considered to be an endogenous dithiol-reducing factor. L-Cystine transport analysis showed that mitogenically stimulated PBMC and PHA blasts incorporated L-cystine, whereas resting PBMC did not. Furthermore, ADF as well as 2-ME exhibited an enhancing activity on the L-cystine transport in PHA blasts. Together with the fact that L-cystine transport is a limiting step in glutathione synthesis, these findings suggest that GSH and ADF might cooperate in the thiol-mediated redox regulation process and might also play key roles in cell cycle (late G1 to S) progression of activated lymphocytes. PMID- 8207198 TI - Expression of the homotypic adhesion molecule E-cadherin by immature murine thymocytes and thymic epithelial cells. AB - Cadherins mediate homotypic adhesion between lineage-related cells in epithelia and other tissues. One cadherin, E-cadherin, is also responsible for adhesion of murine epidermal Langerhans cells to keratinocytes in vitro, and may play a role in the localization of Langerhans cells in epidermis. The thymus is another tissue in which important adhesive interactions between bone marrow-derived cells and keratinizing epithelia occur. To determine whether cadherins might be involved in interactions between thymocytes and thymic epithelial cells, we examined thymocytes from C57BL/6 mice of various gestational ages for cadherin expression. Most day 14 (D14) and essentially all D16 isolated fetal thymocytes expressed cell surface E-cadherin. After D16, the proportion of fetal thymocytes expressing E-cadherin and the level of E-cadherin expressed by individual thymocytes decreased with increasing gestational age. A minority of neonatal thymocytes and very few adult thymocytes expressed E-cadherin. E-cadherin was maximally expressed by the least mature (CD4-CD8-, HSA (J11d)high, CD5 (Ly-1)low, CD25 (IL-2R alpha)+) thymocytes. P-cadherin, another epithelial cadherin, was not detected on thymocytes at any stage of development. Immunohistologic studies revealed that thymic epithelial cells also expressed E-cadherin. Similar levels of E-cadherin were expressed by neonatal and adult thymic epithelial cells in situ, and E-cadherin was easily demonstrable on the thymic epithelial cell line, TE-71. In contrast, P-cadherin was transiently expressed by thymic epithelial cells in situ, and only small amounts of P-cadherin were detected on TE-71 cells. These studies demonstrate that thymocytes and thymic epithelial cells each have the capacity to express the homotypic adhesion molecule E-cadherin. E-cadherin may play a role in developmentally regulated interactions between early thymocytes and thymic stromal cells. PMID- 8207199 TI - LFA-1-mediated antigen-independent T cell adhesion is regulated by CD4 and p56lck tyrosine kinase. AB - We examined the role of CD4 and p56lck in the regulation of LFA-1-dependent T cell adhesion to B cells and to fibroblasts expressing ICAM-1 and HLA-DR by using various transfectant constructions. Although CD4 transfection in CD4low HUT78 T cell lines did not significantly modify their maximal binding to B cells and fibroblasts, it made the LFA-1-dependent adhesion sensitive to inhibition by anti CD4 Ab, HIV-1 (env) gp 160, and a 12-mer peptide encompassing the 35-46 sequence of the beta 1 domain of the MHC class II molecule. CD4low HUT78 T cell adhesion to B cells was stable over 60 min, whereas expression of CD4 led to a transient adhesion. In addition, adhesion of CD4+ T cells to MHC class II- B cells was also stable. The CD4-dependent alteration of adhesion required the association of CD4 with p56lck because expression of mutant forms of CD4 unable to bind p56lck resulted in a lack of CD4-dependent regulation of adhesion. Herbimycin A, an inhibitor of tyrosine kinase activity, reversed the effect of CD4 transfection on adhesion. These results indicate that ligand binding to CD4 delivers a signal inducing cell dissociation by activating p56lck tyrosine kinase. This regulatory pathway may provide a quick and reliable way for multiple and subsequent Ag independent adhesion events of CD4+ T cells. PMID- 8207200 TI - Signal transduction mediated by the reconstituted IL-2 receptor. Evidence for a cell type-specific function of IL-2 receptor beta-chain. AB - The binding of IL-2 to its specific receptor (IL-2R) triggers various cellular events including the induction of nuclear proto-oncogenes (c-fos, c-jun and c-myc genes) and the proliferation of hemopoietic cells. In the present study, we have established NIH 3T3 fibroblasts in which the three IL-2R subunits, the alpha chain (IL-2R alpha), the beta-chain (IL-2R beta), and the gamma-chain (IL-2R gamma), are constitutively expressed. The resulting cell lines express high affinity IL-2R on their cell surface at levels comparable with those of IL-2 responsive lymphoid cells. We observed that the high affinity IL-2R in NIH 3T3 fibroblasts can mediate the IL-2-stimulated tyrosine phosphorylation of p42/p44 (mitogen-activated protein kinase) and the induction of the c-fos, c-jun and c myc genes. In NIH 3T3 fibroblasts the high affinity IL-2R bearing a deletion of a region rich in acidic amino acids (the "acidic" region) in the IL-2R beta-chain failed to induce the tyrosine phosphorylation of MAP kinase as well as the expression of the all three nuclear proto-oncogenes. On the other hand, our previous studies had demonstrated that the high affinity IL-2R bearing the same mutant IL-2R beta-chain retained the ability to induce c-myc gene in response to IL-2 in a murine IL-3-dependent pro-B cell line, BAF/B03. Hence, these results reveal the underlying complexity of signal transduction among different cell types. The inability of the reconstituted high affinity receptor to mediate the IL-2-induced proliferation of NIH 3T3 fibroblasts suggests that induction of the three nuclear proto-oncogenes and the tyrosine phosphorylation of mitogen activated protein kinase in NIH 3T3 fibroblasts are not sufficient to induce cellular proliferation. PMID- 8207201 TI - Inhibition of the transendothelial migration of human T lymphocytes by prostaglandin E2. AB - To determine whether part of the anti-inflammatory effects of prostaglandin E2 (PGE2) was related to inhibition of T cell interactions with endothelial cells (EC), the effects of PGE2 and other cAMP-elevating agents on the transendothelial migration of human T cells was examined. Although PGE2 did not effect T cell binding to EC, concentration-dependent inhibition of the transendothelial migration of T cells through unstimulated or IL-1-activated EC was observed. PGE2 inhibited the function of both T cells and EC, with maximal inhibition observed when both T cells and EC were treated with PGE2. However, the inhibitory action of PGE2 could not be ascribed to an effect on the adhesion receptor pair, CD11a/CD18-CD54. The inhibitory effect of PGE2 seemed to relate to its capacity to elevate cellular cAMP levels, because 3-isobutyl-1-methylxanthine enhanced PGE2 activity and dibutyryl cAMP and forskolin also inhibited transendothelial migration. The inhibitory effect of PGE2 and the other cAMP-elevating agents on the function of T cells related in part to suppression of their intrinsic locomotory behavior as random migration in the absence of EC was blocked. In EC, PGE2 and the other cAMP-elevating agents increased the barrier function of EC as evidenced by a decrease in the diffusion of [3H]mannitol through the endothelium. These results indicate that part of the anti-inflammatory action of PGE2 relates to its capacity to suppress the transendothelial migration of T cells by cAMP mediated alterations in the function of both T cells and EC. PMID- 8207202 TI - Control of T lymphocyte activation and IL-2 receptor expression by endogenously secreted lymphokines. AB - The relative contribution of endogenously secreted lymphokines, TNF-alpha and IL 2, to T cell activation has been studied. Interestingly, a neutralizing anti-TNF alpha mAb strongly inhibited the proliferation, IL-2R alpha expression, and activation of the nuclear factor (NF)-kappa B induced on human purified T lymphocytes by an immobilized anti-CD3 mAb (imm.anti-CD3). Furthermore, the addition of exogenous TNF-alpha to T cells activated by imm.anti-CD3 or phorbol esters strongly stimulated all those activities. Similarly, neutralizing anti-IL 2R alpha Abs inhibited the cell proliferation and the IL-2R alpha expression induced by imm.anti-CD3, whereas exogenous addition of IL-2 enhanced both activities. However, exogenous addition of IL-2 did not affect NF-kappa B activation. Cyclosporin A, which prevented lymphokine mRNA transcription, inhibited more than 90% of the IL-2R alpha and NF-kappa B levels induced by TCR/CD3-mediated activation. Exogenous TNF-alpha and IL-2 were equally important to the partial recovery of this IL-2R alpha inhibition, and high doses of both lymphokines together completely abolished the inhibitory effect of cyclosporin A. However, only TNF-alpha (but not IL-2) efficiently recovered the nuclear NF-kappa B levels. Those results indicate that the autocrine secretion of TNF-alpha and IL 2, and not the primary stimulus itself, contribute mostly to the regulation of IL 2R; thereby playing a very important role in quantitative control of T cell proliferation and leaving to the specifically TCR/CD3-derived signals the triggering role in T cell activation. PMID- 8207203 TI - Antigen presentation by human dermal microvascular endothelial cells. Immunoregulatory effect of IFN-gamma and IL-10. AB - Human dermal microvascular endothelial cells (HDMEC) play a central role in many aspects of the inflammatory and immune reactions in skin. HDMEC display a phenotypic diversity ranging from cells with an epithelioid morphology to those that show both morphologic and biochemical characteristics of macrophages. Here it is shown that HDMEC possess the capability to both process and present Ags. T lymphocyte clones specific for peptide p94-104, which are derived from the protein of group I allergen of Dermatophagoides pteronyssinus, a major house dust mite allergen, and restricted by HLADR11, proliferated specifically to stimulation with the group I allergen of D. pteronyssinus and with peptide p94 104 presented by HDMEC. Preincubation for 48 h with IFN-gamma enhanced the expression of class II MHC Ags on HDMEC, which in turn increased the capacity of HDMEC to present Ag. When HDMEC were primed with Ag in the presence of IL-10, a 75% inhibition of Ag-specific T cell proliferation was observed. IL-10 also inhibited T cell proliferation induced by IFN-gamma-stimulated HDMEC. These findings demonstrate that HDMEC possess the ability to process and present Ag to CD4+ T cells and that these reactions are stimulated by IFN-gamma and inhibited by IL-10. The reduced Ag-presenting capacity of HDMEC mediated by IL-10 is not associated with a down-regulation of class II MHC expression. No significant reduction of HLA-DR expression was detected either at the protein or gene level when HDMEC were incubated with IFN-gamma and IL-10 as compared with incubation with IFN-gamma alone. The profound down-regulatory effect of IL-10 on Ag presentation may provide a new pharmacologic approach to control inflammatory responses in skin. PMID- 8207204 TI - HLA-DR3 molecules can bind peptides carrying two alternative specific submotifs. AB - Three different HLA-DR3-specific peptide binding motifs have been proposed. These motifs shared a major hydrophobic anchor at the N-terminus, but differed in the C terminal anchor residues. In the present study, the structural requirements for peptide binding to HLA-DR3 were examined in further detail by using quantitative HLA-DR3-specific binding assays and sets of single substitution analogues of DR3 binding peptides (Lol pollen amino acids 171-190 and sperm whale myoglobin amino acids 132-151). We found that the requirements for binding to HLA-DR3 vary among different DR3 binding peptides; the absence of an anchor or the presence of only a weak anchor residue at either position n or n + 3 can be compensated for by the presence of a strong, positively charged anchor residue at position n + 5. These results explain several of the previously reported differences between DR3 specific peptide binding motifs. To evaluate the predictive value of the thus refined motif, the DR3 binding capacity of an overlapping set of peptides, spanning the entire sequence of the 65-kDa heat shock protein of Mycobacterium tuberculosis was investigated and correlated with the occurrence of the different DR3 motifs. A strong correlation was found between the presence of the refined DR3 motif and peptide binding to purified HLA-DR3 molecules. PMID- 8207205 TI - Structure, chromosomal localization, and methylation pattern of the human mb-1 gene. AB - The Ag receptor on B lymphocytes is a multimeric complex that is composed of an Ag-specific component, surface Ig, which is noncovalently associated with at least two other proteins, Ig alpha and Ig beta. These are the glycoprotein products of the B lineage-restricted mb-1 and B29 genes and are crucial for the cell surface expression and function of the Ag receptor on B lymphocytes. To better understand the regulation of mb-1, we have cloned and sequenced a 5.7-kb genomic DNA fragment that contained the human gene. The overall structure of human mb-1 is very similar to that of the murine gene, including the number and approximate size of exons. The promoter region lacks a TATA element, but contains two copies of an early B cell factor-binding motif, which previously has been shown to be important for murine mb-1 expression. Other structural features include two nuclear factor-kappa B binding sites at the 5' end of the gene and a long stretch of AG rich-sequence between exons 3 and 4, downstream of an Alu repeat sequence that contains a potential stem-loop structure. The mb-1 gene was localized to chromosome 19q13.2-13.3 by a combination of two methods, PCR amplification of DNA from a somatic cell hybrid-mapping panel and fluorescence in situ hybridization. An examination of the methylation pattern revealed a striking correlation between demethylation in the 5' region of the gene and expression of mb-1. The demethylated HpaII/MspI sites are adjacent to the nuclear factor-kappa B-binding motifs, which suggests a role for this transcription factor in the regulation of human mb-1 gene expression. PMID- 8207207 TI - Administration of recombinant human IL-7 to mice alters the composition of B lineage cells and T cell subsets, enhances T cell function, and induces regression of established metastases. AB - These studies investigate the effects of exogenously administered recombinant human IL-7 (rhIL-7) on mouse leukocyte subsets in vivo in normal and tumor bearing mice. The administration of rhIL-7 to normal mice caused a pronounced leukocytosis (three- to fivefold increase over background) in the spleen and lymph nodes, with B-lineage and T cells, NK cells, and macrophages all being increased. CD8+ T cells increased disproportionately, such that the CD4 to CD8 ratio decreased dramatically. The rhIL-7-induced effects were dose-dependent, increased with duration of treatment, and were reversible after cessation of rhIL 7 administration. T cell number increases after rhIL-7 treatment were primarily a result of an expansion of the peripheral T cell population. Importantly, splenocytes from rhIL-7-treated mice have enhanced proliferative responses to various T cell stimuli in vitro and were able to potentiate an allogeneic CTL response in vivo. The rhIL-7-induced changes in T cell number and the CD4 to CD8 ratio also were observed in mice bearing early Renca renal adenocarcinoma pulmonary metastases, and these changes coincided with up to a 75% reduction in pulmonary metastases. Overall, these results demonstrate that the administration of rhIL-7 to mice profoundly increases the number of B and T cells, and reduces the number of pulmonary metastases. The results also suggest that IL-7 may be useful for restoring lymphoid subsets in immunosuppressed hosts and in enhancing T cell-mediated immune responses. Such effects may be useful in the treatment of microbial diseases and cancer. PMID- 8207206 TI - Molecular cloning and characterization of a murine LPS-inducible cDNA. AB - Murine macrophages respond to endotoxins by inducing a vast array of genes that play a major role in the host's response to infection and tumor growth. We have isolated and characterized a 1.8-kb cDNA, designated IRG2, from a cDNA library prepared from RNA isolated from the murine cell line, RAW 264.7, after bacterial LPS stimulation. The cDNA encodes a protein of 47 kDa that is the murine homologue of a small family of proteins described from IFN-induced human cells. The IRG2 message does not appear until 3 h after LPS exposure and its induction is dependent on new protein synthesis. IRG2 induction by LPS is slightly inhibited by the anti-inflammatory steroid, dexamethasone. Increasing cytosolic cAMP with either forskolin, dibutyryl cAMP, or 8-(4-chlorophenylthio)-cAMP caused marked inhibition of the LPS induction of IRG2. In contrast, activation of PKC with phorbol ester potentiated the LPS response. Removing extracellular Ca2+ with EGTA inhibited IRG2 induction; increasing intracellular calcium with the calcium ionophore A23187 led to enhanced levels of the IRG2 transcript. These data suggest that the induction of IRG2 occurs via a PKC pathway. PMID- 8207208 TI - Nitric oxide production by splenic macrophages is not responsible for T cell suppression during acute infection with lactate dehydrogenase-elevating virus. AB - Cellular immune responses of mice are transiently suppressed during acute infection with lactate dehydrogenase-elevating virus (LDV). Immunosuppression of mice correlated with a greatly impaired in vitro proliferative response of the majority of the T cells to Con A or anti-CD3 Abs, which could not be reversed by the addition of rIL-2. We have examined whether the T cell suppression is caused by nitric oxide (NO) produced by activated macrophages, which are observed in acutely infected mice. Spleen macrophages from 3-day LDV-infected mice exhibited a 6- to 10-fold increased potential for producing NO, measured as nitrite or nitrite plus nitrate in the culture fluid, but produced significant amounts of NO in vitro only when incubated with IFN-gamma produced by Con A-stimulated T cells in the spleen cell population. Furthermore, we found that the concentrations of NO produced by macrophages in cultures of spleen cells from LDV-infected mice in the presence of IFN-gamma were insufficient to cause a reduction in the proliferative response of T cells in the spleen cell population. An excess of activated macrophages had to be added to achieve T cell suppression. NO inhibition of Con A-induced T cell proliferation exhibited a very sharp dose response curve. In one experiment little suppression was observed at NO concentrations equivalent to 12 microM nitrite and below, whereas almost complete inhibition was observed at twice the NO concentration. We conclude that NO is not responsible for T cell suppression in LDV-infected mice. PMID- 8207209 TI - Use of N-acetyl cysteine to increase intracellular glutathione during the induction of antitumor responses by IL-2. AB - IL-2 therapy can induce marked oxidative stress via reactive oxygen and nitrogen intermediates. Glutathione, the major intracellular reductant, may become rate limiting to cytotoxic lymphocyte activation and proliferation under these circumstances. N-Acetyl cysteine (NAc-cys) was used to increase intracellular glutathione levels during lymphokine-activated killer (LAK) cell activation by IL 2. Incubation of splenocytes with NAc-cys (0.6 to 1.0 mM) resulted in significant changes in intracellular reduced and total glutathione (92% and 58% increase, respectively) at 96 h. These levels correlated with markedly enhanced cell proliferation (threefold) and cytolytic effector cell generation (> fivefold increase in LU/10(6) cells) induced by the combination of NAc-cys with IL-2. IL-2 exposure by itself unexpectedly increased intracellular reduced glutathione by 43%. IL-2 and NAc-cys were synergistic in increasing glutathione levels (reduced glutathione: 292% increase; total: 251% increase). Inhibition of glutathione synthesis, using L-buthionine-(S,R)-sulfoximine reversed the effects of NAc-cys on intracellular glutathione, as well as cellular proliferation and cytotoxicity. This experiment established that the effects of NAc-cys required de novo glutathione synthesis. In conjunction with IL-2/LAK treatment, oral NAc-cys administration (260 to 900 mg/kg/day for 7 days) significantly decreased tumor progression in a refractory s.c. tumor model. A small fraction of mice (11 to 17%) had complete tumor regressions. NAc-cys may be useful as an adjunct to increase the antitumor activity of IL-2/LAK therapy. PMID- 8207210 TI - Modulation of Fc gamma and complement receptor function by the glycosyl phosphatidylinositol-anchored form of Fc gamma RIII. AB - Human neutrophils express two structurally distinct receptors for IgG, the transmembrane Fc gamma RII (CD32) and the glycosyl-phosphatidylinositol-linked Fc gamma RIII (CD16). To explore the respective functional roles of Fc gamma RII and Fc gamma RIII, we have used anti-receptor mAb fragments coupled with erythrocytes to quantify both individual and cooperative receptor functions. With individual receptor engagement, Fc gamma RII (E-IV.3) was much more efficient than Fc gamma RIIIB (E-3G8) in initiating phagocytosis (p < 0.001). However, when identical total numbers of receptors were engaged, co-ligation of Fc gamma RII and Fc gamma RIIIB resulted in a phagocytic response, which was: 1) greater than that for either receptor alone (> twofold Fc gamma RII alone (p < 0.001) and > 20-fold Fc gamma RIIIB alone (p < 0.001)); 2) greater than the sum of Fc gamma RII and Fc gamma RIIIB (p < 0.001); and 3) comparable to the phagocytic potential of Fc gamma RII in FMLP pre-activated neutrophils. This synergistic capacity of Fc gamma RIIIB also enabled CR phagocytosis. Furthermore, the capacity for Fc gamma RIIIB to interact synergistically with Fc gamma RII was preserved in FMLP preactivated neutrophils. The activation of Fc gamma RII by Fc gamma RIIIB was associated with tyrosine phosphorylation of the Fc gamma RII cytoplasmic domain, which is essential for Fc gamma RII function and which, by analogy to the Ig alpha-chain of the B cell Ag receptor complex, the zeta-chain of CD3, and the gamma-chain of some Fc epsilon Rs and Fc gamma Rs, may enhance the binding and activation of Src or Syk family tyrosine kinases. Thus, Fc gamma RIIIB can affect multiple receptor families and play a role in achieving maximal Fc gamma R capacity, even in stimulated neutrophils in inflammatory sites. PMID- 8207211 TI - Macrophage-derived nitric oxide is involved in the depressed concanavalin A responsiveness of splenic lymphocytes from rats administered morphine in vivo. AB - The present study examined the role of macrophage-derived nitric oxide in the suppressive effect of in vivo morphine administration on Con A-stimulated proliferation of splenic lymphocytes in rats. The results showed that concentrations of nitrite are significantly greater in Con A-stimulated splenocyte cultures from morphine-treated rats than in cultures from saline treated rats, and that the depletion of macrophages from splenocyte cultures abolishes the suppressive effect of morphine on Con A-stimulated proliferation. Moreover, the addition of NG-monomethyl-L-arginine (NMMA) to Con A-stimulated splenocyte cultures attenuates the suppressive effect of morphine on mitogenic responsiveness. The addition of excess L-arginine to splenocyte cultures containing NMMA reverses the effect of NMMA and restores morphine's suppressive effect on Con A-stimulated proliferation, but the addition of D-arginine to splenocyte cultures containing NMMA does not restore the suppressive effect of morphine. Taken together, these findings demonstrate that the suppressive effect of in vivo morphine administration on Con A-stimulated proliferation of splenic lymphocytes involves macrophage-derived nitric oxide. PMID- 8207212 TI - Protective effect of an adenosine kinase inhibitor in septic shock. AB - Adenosine exhibits potent anti-inflammatory activities but its therapeutic use is limited by cardiovascular side effects. Inhibitors of an enzyme involved in adenosine metabolism, adenosine kinase (EC 2.7.1.20), were evaluated for their ability to enhance endogenous adenosine production. One novel adenosine kinase inhibitor, GP-1-515, was studied in two models of septic shock to assess its protective effects. GP-1-515 significantly decreased mortality in mice that received a lethal i.v. injection of endotoxin. The beneficial effect was accompanied by decreased neutrophil accumulation in the lungs and was reversed by an adenosine receptor antagonist, implying that the effects were mediated by endogenous adenosine. Plasma levels of TNF-alpha, but not IL-1 alpha or IL-6, were lower in the GP-1-515-treated animals. In a second model of sepsis, GP-1-515 increased survival in bacterial peritonitis in rats. The mechanism of action in both models was likely multifactorial, including adenosine-mediated inhibition of neutrophil adhesion, cytokine production, and oxygen radical generation. Adenosine kinase inhibitors have potent anti-inflammatory effects in vitro and in vivo and represent a novel therapeutic approach to the treatment of inflammatory diseases. PMID- 8207213 TI - Inhibition of ceramide pathway does not affect ability of TNF-alpha to activate nuclear factor-kappa B. AB - TNF-alpha is a multifunctional cytokine that has been shown to activate a number of intracellular second messenger pathways. Recent studies demonstrate that the sphingomyelinase-ceramide pathway plays a potential role in the activation of nuclear factor-kappa B (NF-kappa B) by TNF-alpha. The following experiments both confirm that the addition of ceramide to cells can activate NF-kappa B and demonstrate that a 48-h pretreatment with phorbol 12-myristate (PMA) results in the loss of the ceramide-induced NF-kappa B response. In parallel experiments, in which SW480 cells were pretreated with PMA, TNF-alpha provided a signal resulting in the nuclear translocation of NF-kappa B that was similar to untreated cells. These data combined suggest that additional pathways exist that TNF-alpha can use for the activation of NF-kappa B. Supplementary data demonstrates that TNF-alpha, ceramide, and PMA activate a human cytomegalovirus-(HCMV) beta gal construct (promoter is responsive to NF-kappa B) that was stably transfected into the TNF receptor-bearing tumor cell line, SW480. PMA pretreatment of these cells resulted in a significant decrease in both the PMA and ceramide generated responses, 6% and 0% of controls, respectively. However, the response generated by TNF-alpha was not inhibited significantly (96% of control cells). This data suggests that although ceramide and 1,2-diacylglycerol (DAG) pathways may contribute to TNF alpha activation of NF-kappa B, impedance of these pathways does not block TNF alpha from activating NF-kappa B nor induction of the functional activation of the NF-kappa B responsive reporter construct, HCMV. PMID- 8207214 TI - Substrate specificities of murine C1s. AB - An early step in the initiation of the classical C pathway is the proteolytic activation of component C4 by subcomponent C1-s. We have examined the substrate specificity of murine C1-s (mC1-s) by measuring its proteolytic activity on human and murine C4, and on the murine C4 isotype designated sex-limited protein (Slp). The latter substrate was examined because previous studies have demonstrated that Slp is not cleaved by C1-s, and hence Slp has been assumed to be nonfunctional in the C pathways. Those earlier studies used human, not murine, C1-s, however; a recent report has suggested that Slp is an essential component of a novel complement activation pathway and that the previous failure to observe cleavage of Slp is probably the result of a species incompatibility between Slp and the heterologous human C1-s (hC1-s). The present studies do not support this idea, as we found no evidence of cleavage of Slp by homologous murine C1-s even at enzyme concentrations 10-fold higher than that necessary for 50% cleavage of murine C4 (mC4). We did find a species-specific affect in the cleavage of mC4, where mC1-s is about 10-fold more effective than heterologous hC1-s in cleaving mC4, but mC1 s itself does not distinguish between human and murine C4, cleaving both equally well. Hence mC1-s does not exhibit the species specificity previously found for hC1-s, which shows a several hundred-fold preference for homologous human C4 over murine C4. PMID- 8207215 TI - Identification of a novel 33-kDa C1q-binding site on human blood platelets. AB - The constitutive expression of a 60-kDa platelet membrane protein (cC1qR) recognizing the collagen-like amino terminal of C1q was previously described. Recently, a novel 33-kDa C1q receptor (gC1qR) that interacts with the globular head region of C1q was identified on Raji cells, as well as PBLs, neutrophils, and eosinophils. The present study demonstrates that polyclonal Abs directed against this novel C1q-binding protein also recognize a 33-kDa platelet membrane constituent on Western blots. Interestingly, Ab reactivity with platelets in suspension was minimal, but increased nearly 10-fold after platelet adhesion to collagen, fibrinogen, or fibronectin-coated surfaces. Similar increases in Ab reactivity were not achieved after platelet stimulation in suspension, even with strong agonists such as thrombin or A23187. Platelet function studies, however, demonstrated that both the globular C-terminal domain of C1q and the collagen like N-terminal region participate in platelet aggregation in response to C1q multimers. Moreover, a synthetic 18 amino acid peptide (X18) corresponding to the amino terminal sequence of the cloned Raji cell gC1qR inhibited both platelet adhesion to immobilized C1q and aggregated C1q-induced platelet aggregation. Aggregated C1q-induced platelet aggregation was also inhibited by a mAb (1B4) directed against the recombinant gC1qR. The data support the involvement of both carboxy- and amino-terminal regions of C1q in platelet-C1q interactions, and suggest a role for the gC1qR in this process. PMID- 8207216 TI - Kirsten sarcoma virus-immortalized mast cell lines. Reversible inhibition of growth by dexamethasone and evidence for the presence of an autocrine growth factor. AB - Expansion of mast cell numbers occurs in vivo during certain inflammatory reactions, including active fibrosis, parasite infestations, and immediate hypersensitivity reactions. T cell-produced cytokines, including IL-3 and IL-4, are thought to control this mast cell proliferation in part, and glucocorticoid regulation of T cell-produced cytokines is thought to account for diminished mast cell proliferation during administration of glucocorticoids in vivo. Here we show that glucocorticoids have a direct inhibitory effect on proliferation of Kirsten sarcoma virus-immortalized mast cells (KiSV-MC) in vitro, with an ID50 of 1.0 +/- 0.2 nM dexamethasone (mean +/- SD, n = 4). At 10 nM dexamethasone, KiSV-MC proliferation was inhibited by 83 +/- 5% (mean +/- SD, n = 4). As determined by trypan blue staining and [3H]TdR incorporation, the glucocorticoid-mediated growth inhibition was due to diminished mast cell proliferation rather than cell death and was completely reversible after 6 days of glucocorticoid treatment. By cell cycle analysis, glucocorticoids diminished the percentage of mast cells in S phase and increased the percentage in G0-G1 phase. Although we show that the KiSV MC proliferate via an autocrine mechanism, glucocorticoid treatment of the KiSV MC did not inhibit their production of the autocrine growth factor. During 6 days of treatment with 1 to 1000 nM dexamethasone, mast cell carboxypeptidase activity increased by a maximum of 3.5-fold. In contrast, total chymotryptic and tryptic esterase activities diminished by as much as 40% with dexamethasone treatment. We conclude that glucocorticoids directly affect mast cell growth and differentiation at levels equal to the reported Kd for glucocorticoid receptors on other immune cells. PMID- 8207217 TI - Signal transduction pathway in human polymorphonuclear leukocytes for chemotaxis induced by a chemotactic factor. Distinct from the pathway for superoxide anion production. AB - The tyrosine kinase inhibitors erbstatin and herbimycin A inhibited the chemotactic response to FMLP (2 x 10(-7) M) and the superoxide anion (O2-) production stimulated by FMLP (1 x 10(-6) M) in human polymorphonuclear leukocytes (PMN) in similar manners. These compounds also inhibited phospholipase D (PLD)-catalyzed breakdown of phosphatidyl choline, suggesting a possible link between tyrosine kinase and PLD. In the presence of propranolol (phosphatidic acid (PA) phosphohydrolase inhibitor), or ethanol, the activation of PLD results in the modulation of PA and/or diglyceride (DG) generation, producing an irregularity in O2- production. However, PMN motility was not affected in these conditions. These results suggest that PLD is a downstream effector of FMLP induced tyrosine kinase activation that leads to activation of the PMN superoxide release but not to chemotactic migration. In contrast, the tyrosine kinase inhibitors did not inhibit inositol 1,4,5-triphosphate generation and increase of intracellular concentration of free calcium. Furthermore, a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), did not affect the migration of PMN and the activation of PLD induced by FMLP at concentrations of less than 50 microM. These results support the premise that there is a specific signaling pathway for chemoattractant-induced PMN locomotion. PMID- 8207218 TI - TNF-beta produced by human T lymphotropic virus type I-infected cells influences the proliferation of human endothelial cells and fibroblasts. AB - Human T lymphotropic virus type I (HTLV-I) is linked to adult T cell leukemia as well as to HTLV-I-associated myelopathy/tropical spastic paraparesis. In this report, we studied the effects of HTLV-I-infected cell supernatants on HUVEC, fibroblasts, and glioma cells. The HTLV-I-infected cell supernatants (HUT102 and MT-2) strongly inhibited the proliferation of HUVEC, although they enhanced the proliferation of the fibroblasts. Regarding the glioma cells, only the MT-2 supernatant showed weak inhibitory effects on the proliferation. However, the HTLV-I-uninfected cell supernatants showed no effects on these target cells. The biologic activities of both HUT102 and MT-2 supernatants were found to be dose dependent and were reduced by heat treatment at 100 degrees C for 5 min, but not at 56 degrees C for 30 min. These activities were not dependent on the concentrations of HTLV-I viral particles and were only minimally affected by the presence of anti-HTLV-I Abs. A bioassay of various cytokines revealed that the activity of TNF was much higher in the HUT102 and MT-2 supernatants than in the HTLV-I-uninfected cell supernatants (MOLT-4, Jurkat, and K-562). rTNF-alpha and rTNF-beta also showed strong inhibitory effects on HUVEC as well as on the enhancement of the fibroblast growth. With the use of Sephadex G-100 column chromatography, we obtained the highest activities from the 60- through 70-kDa fractions of the HUT102 supernatant and some activities from the 20- through 30 kDa fractions. The biologic activities of both the whole HUT102 supernatant and its active fractions were completely blocked by anti-TNF-beta mAb, although they were not blocked by anti-TNF-alpha mAb. In a Western blot assay, the 25- and 27 kDa bands of TNF-beta were shown clearly in the HUT102 supernatant, although no TNF-alpha bands appeared. These findings suggest that TNF-beta is present in either its oligomeric or monomeric form in the HTLV-I-infected cell supernatants and is also mainly responsible for the supernatants' effects on HUVECs and fibroblasts. PMID- 8207219 TI - Overexpression of zinc-finger transcription factor Z-225/Egr-1 in synoviocytes from rheumatoid arthritis patients. AB - In rheumatoid arthritis (RA) the proliferation of synovial lining cells appears to be one of the initial pathologic changes that contributes to the destruction of articular joints. To understand the pathomechanisms involved in these functional changes, we analyzed the transcriptional regulation of the zinc-finger gene 225 (Z-225/Egr-1), a transcription factor expressed in the immediate early events of cellular activation. We found that Z-225 transcripts were significantly up-regulated in RA synoviocytes. In primary and long term culture Z-225 was spontaneously transcribed at elevated levels. In situ hybridization of zinc finger probe showed characteristic Z-225 transcripts in RA synovial tissues. Identity of these signals to the Z-225 gene product were confirmed in freshly isolated synovial tissue by enzymatic amplification of cDNA by the PCR technique. Z-225 transcripts were also detected and characterized in a cDNA library established from a RA synovial explant. We therefore conclude that RA synoviocytes spontaneously produce Z-225 gene products at elevated levels. Because early growth response gene Z-225 is involved in the regulation of expression of other genes such as proto-oncogenes c-ras and c-sis, which are also up-regulated in the RA synovium, activation of Z-225 transcription in RA may represent a key event in articular joint destruction. PMID- 8207220 TI - Restoration of IFN-gamma production and lymphocyte proliferation in visceral leishmaniasis. AB - Visceral leishmaniasis is associated with a marked depression of T cell responses, which has been characterized by the absence of IL-2 and IFN-gamma production by lymphocytes on in vitro stimulation with Leishmania Ag. The aim of this study was to evaluate both the mechanism of these immunologic abnormalities and the restoration of in vitro T cell responses to Leishmania Ags. A total of 15 untreated visceral leishmaniasis patients were evaluated. Although IFN-gamma and IL-4 levels in the supernatants of lymphocyte cultures were very low or absent, mRNA for these cytokines and for IL-10 were observed in PBMCs. Addition of IFN gamma plus IL-2 enhanced lymphocyte proliferation by 158%. Restoration of T cell proliferative responses and IFN-gamma production was also observed by the addition of a neutralizing mAb alpha-IL-10. Neutralizing mAb alpha-IL-4 did not restore T cell responses but alpha-IL-10 and alpha-IL-4 mAbs had a synergistic effect on lymphocyte proliferation. The IFN-gamma levels in supernatants of lymphocyte cultures stimulated with Leishmania chagasi Ag or L. chagasi Ag plus alpha-IL-4, alpha-IL-10, or alpha-IL-4 plus alpha-IL-10 mAbs were 26 +/- 30 pg/ml, 41 +/- 18 pg/ml, 146 +/- 73 pg/ml, and 174 +/- 106 pg/ml, respectively. These data indicate that Th2 cell activation occurs in visceral leishmaniasis and that in vitro production of IFN-gamma and lymphocyte proliferation can be restored by blocking the inhibitory effect of the Th2 cytokines on mononuclear cells. PMID- 8207221 TI - Expression of homing and adhesion molecules in infiltrated islets of Langerhans and salivary glands of nonobese diabetic mice. AB - The nonobese diabetic mouse is a relevant model for insulin-dependent diabetes mellitus which results from the destruction of pancreatic beta cells by mononuclear cells infiltrating the islets of Langerhans. Other organs such as salivary glands display inflammatory infiltration. Using immunohistochemical and flow cytometry analyses, we have studied the expression of diverse homing and adhesion molecules in salivary glands and the pancreas in nonobese diabetic mice. In salivary glands, ICAM-1 was expressed by endothelial and dendritic cells within the lymphocytic infiltration. HEV-like structures expressing PNAd were observed in the areas of lymphocytic infiltration whereas MAdCAM-1 was absent. Lymphocytes infiltrating salivary glands expressed LFA-1 and Pgp-1 although Mel 14 Ag was absent. In infiltrated islets, ICAM-1 was expressed by endothelial cells, dendritic cells, and mononuclear cells. We confirm the presence of HEV like structures expressing MAdCAM-1 and PNAd in inflamed islets. With regard to peripheral lymphocytes, the proportion of CD4 and CD8 cells expressing Mel-14 was decreased in the infiltrated islets, whereas the expression of LFA-1, Pgp-1, and LPAM-1/2 was increased. B lymphocytes exhibited up-regulation of LPAM-1/2. Moreover, the proportion of CD4, CD8, and B lymphocytes expressing CD69 was increased in the pancreas. These results indicate that first, infiltration of islets of Langerhans results at least partly from modifications of adhesion molecule expression in the pancreas, which allow extravasation of mononuclear cells into the islets via at least three different pathways; and second, that activated cells are concentrated in the infiltrates as compared with peripheral lymphoid organs. PMID- 8207223 TI - Structure-function studies on a polyreactive (natural) autoantibody. Polyreactivity is dependent on somatically generated sequences in the third complementarity-determining region of the antibody heavy chain. AB - SMI is a previously characterized IgM kappa polyreactive (natural) autoantibody. The variable regions of the heavy and light chains of SMI are respectively encoded by a nonmutated VH1 gene, designated 51p1, and a conserved nonmutated V kappa gene, designated Humkv325. These V genes seem to be over-represented in the autoimmune and fetal B cell repertoires, and to be frequently expressed in malignant B cells during certain lymphoid proliferations such as chronic lymphocytic leukemia. Polyreactive natural autoantibodies are thought to rely mainly on the use of such V genes in germ-line configuration. However, this model underestimates the contribution of the somatically generated heavy chain third complementarity-determining region (HCDR3) to autoantibody specificity. We used oligonucleotide site-directed mutagenesis to permute the sequence of the SMI HCDR3 to generate a family of mutant proteins, each of which differed from the original SMI-IgM kappa by one amino acid residue. This allowed us to examine the relative contribution of selected amino acid residues in this region to the binding affinity of SMI against a panel of self-Ags. We found that a single amino acid substitution within the HCDR3 could dramatically alter the specificity of this autoantibody. Some substitutions abrogated the reactivity with all the tested Ags, whereas others changed the affinity or spectrum of reactivity for certain self-Ags. These results demonstrate that the autoantibody-binding activity of these conserved autoantibody-associated germ-line V genes is dependent upon heavy chain junctional sequences that are generated somatically during Ig gene rearrangement. PMID- 8207222 TI - Increased TGF-beta and decreased oncogene expression by omega-3 fatty acids in the spleen delays onset of autoimmune disease in B/W mice. AB - This study was designed to investigate the mechanisms by which marine lipids rich in long chain omega-3 fatty acids inhibit autoimmune disease and prolong the survival rate in female (NZB/NZW) F1 (B/W) mice, an animal model for human SLE. Nutritionally adequate semipurified diets containing at 10% either corn oil (CO) or fish oil (FO) were fed from 1 mo of age and were monitored for proteinuria and survival. Proteinuria was detected earlier and became progressively severe in CO fed mice. The average life span was significantly shortened by the CO diet (266.7 days +/- 12.5), whereas FO extended the survival significantly (402.1 days +/- 26.1; p < 0.001). A cross-sectional study at 6.5 mo of age revealed an increased proliferative response to T cell mitogens including bacterial superantigens and decreased serum anti-dsDNA Ab titers in the FO group compared with the CO group. Furthermore, splenocytes from the FO group when stimulated with Con A had higher IL-2 and lower IL-4 production similar to that of young (3.5 mo) mice. Flow cytometric analyses of splenocytes revealed lower Ig+, higher lymphocyte endothelial cell adhesion molecule-1, and lower Pgp-1+ cells within CD4+ and CD8+ subsets in FO-fed mice. Also, elevated IL-2 and IL-4 and significantly higher TGF beta 1 and lower c-myc and c-ras mRNA expression and higher TGF-beta 1 and significantly lower c-Myc and c-Ha-Ras proteins were detected in spleens of FO fed mice. Fatty acid analysis revealed significantly higher linoleic (18:2 omega 6) and arachidonic (20:4 omega-6) acid levels in splenocytes of the CO-fed group and higher eicosapentaenoic (20:5 omega-3) and docosahexanoic (22:6 omega-3) acid levels in the FO-fed group, indicating that changes in membrane fatty acid composition may contribute to the altered immune function and gene expression during the development of murine SLE. PMID- 8207224 TI - Pathogenesis of hyperacute experimental autoimmune myasthenia gravis. Acetylcholine receptor/cholinergic site/receptor function/autoimmunity. AB - Three mAbs, mAbs 249E, 370, and 383C, directed against the alpha-bungarotoxin (alpha BgTx) binding site of the acetylcholine receptor (AChR) induce a hyperacute form of experimental autoimmune myasthenia gravis (EAMG), characterized by death within hours of mAb injection. To analyze the mechanisms of this effect, purified AChR-mAb complexes were investigated for their ability to bind the cholinergic agonist carbamoylcholine and to undergo agonist-induced activation of the cholinergic ionophore. The three mAbs inhibited carbamylcholine binding, and, conversely, their binding to AChR was inhibited by carbamylcholine. All three completely inhibited carbamylcholine-induced T1+ influxes to AChR-rich vesicles. These data indicate that the severe hyperacute EAMG induced by these mAbs results from blockage of AChR function and that the role of such potent Abs (even if present in small amounts) in the pathogenesis of human myasthenia gravis deserves further investigation. PMID- 8207225 TI - Defective production of anti-inflammatory cytokine, TGF-beta by T cell lines of patients with active multiple sclerosis. AB - Activated T lymphocytes play an important role in the pathogenesis of multiple sclerosis (MS). These T cells secrete both pro- and anti-inflammatory cytokines. We have studied the production of these two kinds of cytokines by PBL of patients with MS and compared it with normal controls and other autoimmune diseases (OAD). PBL of 29 patients with MS, 14 patients with OAD, and 14 healthy normal controls were cultured for 5 wk. PBL of MS patients produced more pro-inflammatory cytokines, IL-2, IFN-gamma and TNF/lymphotoxin, and less anti-inflammatory cytokine, TGF-beta, during wk 2 to 4 in culture than PBL of normal controls. PBL of MS patients also produced more IL-2 and TNF/lymphotoxin than PBL of OAD patients. Decreased TGF-beta production by lymphocytes of patients with MS correlated directly with disease activity. MS patients with active disease produced less TGF-beta than MS patients with stable disease. The cells producing TGF-beta were primarily CD8+ T cells and CD45RA+T cells. These findings emphasize the complexity of immune response in MS patients and suggest that the increased production of pro-inflammatory cytokines by lymphocytes of patients with MS, combined with the decreased production of TGF-beta (anti-inflammatory cytokine), may play an important role in the mechanisms and manifestations of MS. PMID- 8207226 TI - T-B collaboration for autoantibody production in lpr mice is cognate and MHC restricted. AB - A central question in autoimmunity is the mechanism of T cell help for autoantibody production. For responses to exogenous Ag, T-B collaboration is restricted by MHC class II molecules. To determine whether T cell help that leads to autoantibodies in murine SLE is also MHC-restricted, we have constructed bone marrow chimeras with Ig heavy chain (lgh) allotype- and I-A-congenic donor B6/lpr mice and I-A-congenic recipients. Developing T cells were thus positively selected in the host thymus to interact with B cells bearing I-A of one haplotype or the other. Additional control host mice were heterozygous for I-A expression, allowing T helper cell selection for both I-A haplotypes. Five months after reconstitution, serum total IgG2a, IgM, IgG2a antichromatin, and IgM rheumatoid factor were quantitated by allotype-specific ELISA. Data showed that whereas substantial numbers of B cells were present from both donor strains in all mice, autoantibody production was overwhelmingly from those donor B cells expressing the same I-A haplotype as the host. Sera from the I-A heterozygous control recipient group had roughly equal quantities of autoantibodies of both allotypes, as expected. The finding of MHC class II restriction implies that the T cell help that drives autoantibody production in lpr mice is delivered through cognate (cell-to-cell) interactions and not by soluble factors alone. PMID- 8207227 TI - High expression of V gamma 8 is a shared feature of human gamma delta T cells in the epithelium of the gut and in the inflamed synovial tissue. AB - We have analyzed the V-gene usage in gamma delta T cells of the human gut and joint by using a new mAb (B18) specific for V gamma 8 of human TCR-gamma delta+ T cells. The B18+ population constituted a minor subset of the gamma delta T cells in peripheral blood (PB) of healthy persons (6 +/- 5%) and only 1 of 35 gamma delta T cell clones analyzed was positive. In contrast, the B18+ subset was a dominant gamma delta T cell population among intraepithelial lymphocytes (IEL) derived from the human intestine (74 +/- 29, p < 0.002), and two of three IEL clones from patients with coeliac disease were B18+. Interestingly, a higher proportion of B18+ gamma delta T cells was found in the synovial fluid of patients with rheumatoid arthritis (RA) (21 +/- 18%, 0.02 < p < 0.05) compared with normal PB. Furthermore, the B18+ subset was more frequent among IL-2 expanded gamma delta T cells (42 +/- 20%) derived from synovial tissue than among IL-2-expanded cells derived from synovial fluid (p < 0.002) and PB from RA patients (p < 0.02) as well as normal PB (p < 0.002). The V-gene usage of 13 gamma delta T cell clones from the synovial fluid of arthritic patients was analyzed. All B18+ clones (n = 7) expressed mRNA for V gamma 8 together with mRNA for V delta 1 (n = 5) or mRNA for V delta 3 (n = 2). None of the B18- clones expressed V gamma 8 (n = 6). We conclude that the gamma delta T cell that expresses V gamma 8, together with mainly V delta 1, is a major gamma delta T cell subset among the IEL of the gut and a highly frequent subset in the synovial tissue of patients with RA. This subset may correspond to the mouse V gamma 7+ IEL, which has a high degree of amino acid sequence homology with the human V gamma 8 protein. PMID- 8207228 TI - Transcriptional regulation of CD6 expression on human T lymphocytes by phorbol ester. AB - Activation of protein kinase C (PKC) has emerged as a major common signal transducing mechanism for T cell activation and regulation of expression of T cell surface glycoproteins. Surface expression of the CD6 Ag is known to increase with T cell activation and CD6 itself may be involved in regulation of T cell activation. Therefore, we performed experiments to determine whether activation of PKC by phorbol ester induced an increase in CD6 expression and to investigate the mechanisms of such an effect. CD6 surface expression was up-regulated substantially in response to PMA on both mature and immature T cells, but only negligibly on B cell lines. This increase was blocked by PKC inhibitors. The PMA induced increase in CD6 surface expression was accompanied by an increase in total CD6 protein, as detected by using Western blot analysis of whole cell lysates. After PMA stimulation, Northern blot analysis showed that steady state levels of CD6 mRNA increased in response to PMA treatment. This increase was blocked by cycloheximide, demonstrating that it was dependent on new protein synthesis. Nuclear run-on analysis showed that the rate of CD6 mRNA transcription increased by approximately two to threefold after PMA stimulation of Jurkat cells. Experiments in which we used actinomycin D showed that PMA had no significant effect on the t1/2 of CD6 mRNA. The data suggest that the effect of PMA on CD6 expression is mediated primarily by an increase in CD6 mRNA transcription after PKC activation. mAbs were used to determine whether augmented CD6 expression could be induced by perturbation of specific T cell surface molecules. Up-regulation of CD6 expression occurred when thymocytes were cultured with anti-CD2 Abs, but not with Abs to other functional T cell surface structures, and not when mature T cells were cultured with the anti-CD2 mAbs. Up regulation of CD6 expression by activation of PKC, triggered in thymocytes by ligation of CD2, could allow CD6 to provide additional regulatory signals required for events in later stages of T cell activation and differentiation. PMID- 8207229 TI - Quantitative differences in cell surface expression of class I MHC antigens on murine epidermal Langerhans cells. AB - Epidermal Langerhans cells are derived from cells of bone marrow origin and, as the primary APC population in the skin, are responsible for initiation of many immune responses. Consequently, cell surface expression of MHC Ags by Langerhans cells is central to their function. Although murine Langerhans cells express class II MHC Ags at high levels, their level of expression of class I MHC has been controversial. In this study, cell surface expression of multiple individual class I MHC Ags on murine epidermal Langerhans cells was analyzed using quantitative immunofluorescence. It was found that Langerhans cells differentially express products of distinct class I genes. Langerhans cells expressed low cell surface amounts of H-2K and Qa-2, whereas expression of surface H-2D and H-2L by the same cells was high. Murine epidermal Langerhans cells therefore express low cell surface amounts of some but not all class I MHC Ags. Differential surface expression of products of distinct class I MHC genes by Langerhans cells may have a profound effect on cutaneous immune responses. PMID- 8207230 TI - Characterization of a new functional TCR J delta segment in humans. Evidence for a marked conservation of J delta sequences between humans, mice, and sheep. AB - Through analysis of TCR delta-chain cDNA derived from human gamma delta T cell clones and polyclonal gamma delta T cell lines, we isolated a novel functional J delta gene segment (termed J delta 4) whose genomic fragment has been mapped within the TCR-delta locus between J delta 2 and J delta 1. Frequency of J delta 4 use was estimated among adult gamma delta PBL by using V delta 1, V delta 2, and V delta 5 genes. In all cases, this new J element was used at a low, albeit significant frequency, close to that of J delta 2. Finally, like human J delta 1 and J delta 2, which show a high degree of homology with their counterparts in the mouse and sheep, but unlike other J gamma, J beta, or J alpha elements, J delta 4 turned out to be highly homologous to a recently described ovine J delta. These results suggest the existence of strong selective pressures, possibly linked to an Ag-driven process, leading to specific conservation of J delta sequences among these three species. PMID- 8207231 TI - Upstream NFIL-6-like site located within a DNase I hypersensitivity region mediates LPS-induced transcription of the murine interleukin-1 beta gene. AB - To define the cis-acting elements that regulate LPS-stimulated IL-1 beta gene transcription, we analyzed the murine IL-1 beta gene by digestion with DNase I. At least two hypersensitive sites were located between 2200 and 2600 bp upstream of the transcription start site in mononuclear phagocytes, but not in an IL-1 nonproducing immature T cell line. Specific DNA sequences required for LPS induction of IL-1 beta gene expression were identified within the DNase I hypersensitive (DH) region using transfection of reporter constructs that contained portions of the IL-1 beta 5'-flanking region. Two specific DNA sequences were targets for nuclear factor binding as assessed with use of electrophoretic mobility shift analysis (EMSA). One site contained a consensus sequence for NFIL-6 binding. Base substitutions within this NFIL-6 site resulted in virtual elimination of LPS-induced IL-1 beta gene transcription. Introduction of multimers of the NFIL-6-like sequence immediately 5' to homologous or heterologous promoters conferred LPS-induced transcription, indicating that this NFIL-6-like consensus site was a transcriptional activator. Anti-C/EBP beta (NFIL 6) and anti-C/EBP delta (NFIL-6 beta) Abs identified both of these proteins in complexes formed between the NFIL-6-like element and mononuclear cell nuclear extracts. C/EBP delta (NFIL-6 beta) was not detected in complexes utilizing extracts from the IL-1 nonproducing T cell line. These data are consistent with the requirement for C/EBP beta (NFIL-6) and C/EBP delta (NFIL-6 beta) in the activation of murine IL-1 beta gene expression by endotoxin. PMID- 8207232 TI - Synergistic transcriptional activation of the IL-8 gene by NF-kappa B p65 (RelA) and NF-IL-6. AB - Transcriptional activation of the IL-8 gene by several inflammatory mediators, including the cytokines IL-1 and TNF-alpha, is mediated through sequences located between nucleotide -94 and -71 of the IL-8 promoter. Because adjacent binding sites for the inducible transcription factors NF-kappa B and NF-IL-6 are located within this region, we examined the functional interaction of these two transcription factor families in IL-8 gene regulation. Maximal transcriptional activation by PMA in Jurkat T lymphocytes was shown to require intact binding sites for both NF-kappa B and NF-IL-6. Electrophoretic mobility shift analysis indicates that NF-IL-6, as well as other related members of this family, bind specifically to the NF-IL-6 site in the IL-8 promoter. In addition, NF-kappa B p65 (RelA), but not NF-kappa B p50 (NFKB1), binds specifically to the NF-kappa B site. When incubated together, RelA and NF-IL-6/C/EBP form a ternary complex with this region of the IL-8 promoter; this binding is dependent on intact binding sites for both NF-IL-6 and RelA. Transient cotransfection analyses indicate that the cooperative association of NF-IL-6 and RelA with the IL-8 promoter results in synergistic transcriptional activation. Mutational analyses of RelA demonstrate that the C-terminal transactivation domain and the DNA binding domain are required for synergistic activation with NF-IL-6. In addition, overexpression of the NF-kappa B inhibitor molecule, I kappa B, abolished the RelA- and RelA/NF-IL 6-dependent synergistic activation. These data demonstrate that RelA and members of the C/EBP/NF-IL-6 family can functionally cooperate in transcriptional activation of the IL-8 gene and suggest a common mechanism for inducible regulation of cytokine gene expression. PMID- 8207233 TI - IL-10-induced factors belonging to the p91 family of proteins bind to IFN-gamma responsive promoter elements. AB - Expression of the gene encoding the high affinity IgG receptor (Fc gamma RI) is stimulated by IFN-gamma through a promoter element designated gamma-IFN activation site (GAS). This sequence binds a transcription factor designated gamma-IFN activation factor (GAF). GAF-GAS complexes contain an IFN-regulated 91 kDa protein (p91). In mouse peritoneal macrophages, IL-4 and IL-10 influenced both basal and IFN-gamma-induced expression of Fc gamma RI in opposite ways: IL 10 was stimulatory and IL-4 repressed Fc gamma RI expression. IL-4 or IL-10 did not affect the activation of GAF by IFN-gamma, but both activated the binding of latent, receptor-activated factors (RAFTs) to the Fc gamma RI GAS. RAFTs-IL-4 and -IL-10 migrated similarly in electrophoretic mobility shift assays but could be distinguished through their specificities for different GAS sequences and their reactivity with anti-p91 antisera. These experiments also revealed two distinct RAFTs-IL-10 to be members of the p91 family of proteins. The data suggest GAS related elements to integrate signals from IFN-gamma-, IL-4- and IL-10-activated signaling paths. PMID- 8207234 TI - Bovine conglutinin gene exon structure reveals its evolutionary relationship to surfactant protein-D. AB - Bovine conglutinin (BC), a member of the mammalian C-type collectin subfamily, is a serum protein synthesized in liver that is believed to play a role in natural host defense. Previously, we have characterized a full length BC cDNA and we now describe the partial characterization of a genomic clone that encodes for the BC gene (CGN1). BC is encoded by nine exons spanning > 11 kb and has been localized previously to band 18 of bovine (Bos taurus) chromosome 28. Genomic sequencing demonstrated that the signal peptide/amino-terminal domain, the carbohydrate recognition domain, and the linking peptide, a domain between the collagenous region and the carbohydrate recognition domain, are each encoded by a single exon. The collagenous domain is split into five exons, with the 5' most region being located within the exon that also encodes the signal peptide/amino terminus. The remaining four collagenous domain exons are tandemly arranged with lengths of 117, 108, 108, and 117 bp, respectively. Overall, the BC genomic organization is very similar to that of the human surfactant protein-D gene, SFTP4. On the basis of identical collagen domain structures, we suggest that conglutinin and bovine surfactant protein-D evolved from a gene duplication event occurring in Bovidae after divergence from other mammals. PMID- 8207235 TI - Analysis of binding of monoclonal antibody to a malarial peptide by surface plasmon resonance biosensor and integrated rate equations. AB - Using biosensor technology and integrated rate equations, we have developed procedures to determine the kinetic parameters and equilibrium affinity constant of Ag-Ab interactions. The Ag used in these studies was a peptide that represents the major B cell epitope of the circumsporozoite protein of Plasmodium falciparum, a promising malaria vaccine candidate Ag. Measurements of association and dissociation rate constants of this peptide with the mAb 2A10 were determined by fitting integrated rate equations to binding data obtained with a BIAcore surface plasmon-resonance biosensor. We examined whether accurate estimates of initial velocity and final equilibrium levels of binding of Ab to peptides can be obtained using these methods, and whether kinetic rates and equilibrium constants obtained with systematic variation of the experimental parameters conform to a simple bimolecular model of binding. We found that initial velocity was approximately first order with respect to Ab concentration. When we used a series of four sensor cells with different peptides loads, however, we found that the initial velocity of binding appeared to be nearly independent of peptide concentration. Equilibrium analyses yielded dissociation constants of approximately 3 x 10(-7) M. Integrated rate treatment of biosensor data supports a critical examination of the assumptions on which the binding models are based and suggests a need to refine such models. Nevertheless, it provides a powerful quantitative tool for assessing the Ag-Ab binding reaction. PMID- 8207236 TI - IL-4- and IL-5-dependent protective immunity to Onchocerca volvulus infective larvae in BALB/cBYJ mice. AB - A significant reduction in challenge worm survival occurred when BALB/cBYJ mice were vaccinated against Onchocerca volvulus infective third stage larvae (L3) by using irradiated O. volvulus L3. Challenge infections consisted of L3 implanted in diffusion chambers, which were used as a means to contain, and thus efficiently recover, the larvae from the host. The goal of the present study was to describe the mechanism of immune-mediated killing of O. volvulus L3 in diffusion chambers in mice. Direct contact between host cells and parasites was required for killing of larvae in immunized hosts. To define the mechanism of immune-mediated killing in this system, the time of influx of cells and cytokines into the infection site was compared with the time challenge infections were killed. The only cell type that was found to increase in diffusion chambers in immunized mice was eosinophils; maximal levels of eosinophils were coincident with the time of parasite killing. IL-5 was found in diffusion chambers of immunized mice coincident with the time of parasite killing; IL-5 was not found in diffusion chambers recovered from control mice. Significant levels of IFN gamma were absent in the diffusion chambers of both groups. Immunized mice were treated with mAb to eliminate IL-5 or IL-4 to assess the role these cytokines or their by-products play in larval killing. Elimination of either IL-5 or IL-4 significantly reduced the protective effects of vaccination against larval O. volvulus. PMID- 8207237 TI - Treatment of mice with IL-1 before infection increases resistance to a lethal challenge with Salmonella typhimurium. The effect correlates with the resistance allele at the Ity locus. AB - Administration of a single dose of IL-1 alpha to various strains of mice approximately 16 h before a lethal infection with Salmonella typhimurium resulted in a significant augmentation of survival in most Ityr, but in no Itys strains of mice. Lower numbers of bacteria were observed in the liver and spleen in response to IL-1 pretreatment shortly after infection in all Ityr strains of mice tested, including the congenic C.D2-Ityr mice. Treatment with IL-1 alpha after infection had no effect on survival in either Ityr or Itys mice. A combination of IL-1 alpha pretreatment with IL-1 alpha post-treatment did not increase survival over the effect of IL-1 alpha pretreatment alone in Ityr mice and did not increase the survival of the Itys mice. The combination of IL-1 alpha pretreatment with GM-CSF post-treatment was effective in Ityr but not in Itys strains of mice. Thus, IL-1 alpha pretreatment enhances the resistance of Ityr, but not Itys strains of mice to a lethal challenge with S. typhimurium by up-regulating antibacterial mechanisms shortly after infection. PMID- 8207238 TI - Altered tissue distribution of viral replication and T cell spreading is pivotal in the protection against fatal lymphocytic choriomeningitis in mice after neutralization of IFN-alpha/beta. AB - IFN-alpha/beta have been shown to play a central role in the development of lymphocytic choriomeningitis and increasing attention has been focused on this group of cytokines as early regulatory factors directing T lymphocyte responses. In the present study, injection of antiserum to IFN-alpha/beta prevented the development of lymphocytic choriomeningitis, was associated with the absence of detectable expression of early 2'-5' oligo-adenylate synthetase mRNA and coincided with viremia of lymphocytic choriomeningitis virus (LCMV) followed by establishment of a persistent infection. The LCMV-specific cytotoxic T lymphocyte response was unchanged in cervical lymph nodes but decreased in the spleen of anti-IFN-alpha/beta-treated animals. The expression of cytokine mRNA (particularly IFN-gamma) in organs of LCMV-infected mice treated with anti-IFN alpha/beta coincided with infiltration of lymphocytes and tissue destruction. Furthermore, a reduced number of infiltrating leukocytes in the brain and cervical lymph nodes and a low expression of cytokine mRNA in the brain was observed in anti-IFN-alpha/beta-treated animals. In total, the findings support the view that neutralization of IFN-alpha/beta leads to extensive LCMV replication in the viscera. The therapeutic effects of anti-IFN-alpha/beta antiserum seem to be independent of the functional capacity of T cells but probably result in a dispersion of activated T cells throughout the body of LCMV infected mice. Absence of IFN-alpha/beta expression in the central nervous system is proposed as the mechanism behind the IFN-alpha/beta-dependent targeting of T cells to the brain. PMID- 8207239 TI - Differential regulation of granulocyte-macrophage colony-stimulating factor gene expression in human corneal cells by pro-inflammatory cytokines. AB - Neutrophils and Langerhans cells participate in inflammatory reactions within the human cornea. Because granulocyte-macrophage (GM)-CSF is a chemotactic and activating factor for these two cell types, we investigated whether this cytokine is produced by human corneal epithelial cells and corneal fibroblasts. Cultures of each cell type were exposed to increasing concentrations of IL-1 alpha or TNF alpha. Culture supernatants were assayed for GM-CSF by using ELISA and cytokine mRNA levels were monitored by using reverse transcriptase-PCR. IL-1 alpha treatment of both cell types resulted in the appearance of GM-CSF mRNA and the production of > 480 pg protein/10(6) cells. However, TNF-alpha treatment yielded divergent results. Stimulation of epithelial cells with TNF-alpha resulted in the appearance of > 560 GM-CSF mRNA molecules per cell and production of > 1300 pg GM CSF/10(6) cells. In contrast, stimulation of corneal fibroblasts resulted in < 16 GM-CSF mRNA molecules/cell and < 60 pg GM-CSF/10(6) cells. Binding studies with 125I-labeled TNF-alpha revealed that corneal fibroblasts had as many receptor sites as did corneal epithelial cells. Furthermore, corneal fibroblasts could respond to TNF-alpha-receptor-mediated signal transduction because they produced nanogram amounts of IL-6 after being treated with this cytokine. The results suggest that both cell types synthesize GM-CSF in response to IL-1 alpha, but that only corneal epithelial cells produce significant amounts of GM-CSF after TNF-alpha exposure. Differences in the responses of the two cell types to TNF alpha may reflect a means of limiting accumulation of neutrophils and Langerhans cells and, thus, minimize corneal damage. PMID- 8207240 TI - Origin and steady-state turnover of class II MHC-bearing dendritic cells in the epithelium of the conducting airways. AB - Recent studies have identified a contiguous network of class II MHC-bearing dendritic cells (DC) in the airway epithelium of several species, including humans. This network seems comparable to the epidermal Langerhans cell population, comprising up to 700 DC per mm2 of airway epithelium. Moreover, it accounts for virtually all local immunostaining for class II MHC, suggesting an important role in surveillance for inhaled Ag. This study examines the turnover of these airway DC using a radiation chimera model that uses congenic rats expressing different allotypic variants of CD45, detectable via mAbs. Steady state bone marrow renewal of the airway DC population (which is continuously depleted by migration of mature cells to draining lymph nodes) was interrupted via x-irradiation or high-dose dexamethasone, after which the resident population declined by 85% over the ensuing 72 h. After transplantation with congenic bone marrow and an initial lag period for graft establishment, the airway DC population was rapidly restored to preirradiation levels. These findings indicate a half-life of < or = 2 days for airway epithelial DC. In contrast, epidermal Langerhans cell half-life was > or = 15 days. The only comparable (short) half life previously reported for a peripheral tissue DC population, is that derived from the gut wall. This indicates that rapidly turning over DC populations are a unique feature of the major "mucosal" organ systems, which is consistent with these DC playing an important role in surveillance of mucosal tissues for incoming Ag. PMID- 8207241 TI - IL-7 stimulates CSF-induced proliferation of murine bone marrow macrophages and Mac-1+ myeloid progenitors in vitro. AB - The role of IL-7 as an important stimulator of the growth of B and T cell precursors, as well as mature T cells, is well established. In contrast, the role of IL-7 in myelopoiesis has not been characterized thoroughly, and thus, IL-7 has been regarded as a lymphoid lineage-restricted cytokine. However, we have recently reported that IL-7 enhanced CSF-induced myeloid proliferation of primitive murine hematopoietic (Lin-Sca-1+) progenitors, whereas IL-7 did not affect significantly the proliferation of a population of more mature (Lin-) progenitors. The present study was initiated to investigate further whether IL-7 might affect CSF-induced proliferation of subpopulations of committed myeloid progenitors as well as mature bone marrow macrophages. IL-7 enhanced macrophage colony-stimulating factor (CSF-1)-induced colony formation of single bone marrow macrophages 90%, whereas IL-7 alone had no effect. Furthermore, IL-7, in a concentration-dependent manner, increased the proliferation of mononuclear cells expressing the Mac-1 Ag (Mac-1+ mononuclear cells (MNC); CD11b) up to fivefold in response to CSF-1, granulocyte macrophage-CSF (GM-CSF), or IL-3. In contrast, no effect of IL-7 was observed on Mac-1- MNC. The synergistic effect of IL-7 on Mac 1+ MNC was caused by an increase in macrophage colonies (CFU-M) and mixed granulocyte-macrophage colonies (CFU-GM), whereas the total number of granulocyte colonies (CFU-G) was not affected. This suggests that IL-7 can provide proliferative signals to Mac-1+ progenitors with a macrophage potential, but not to progenitors committed to pure granulocyte differentiation. PMID- 8207242 TI - Peripheral blood mononuclear cells stimulated with C5a or lipopolysaccharide to synthesize equivalent levels of IL-1 beta mRNA show unequal IL-1 beta protein accumulation but similar polyribosome profiles. AB - Recent reports suggest that regulation of IL-1 beta gene expression in human monocytes may include translation level as well as transcription level control mechanisms. We studied IL-1 beta expression in PBMC stimulated with recombinant complement protein C5a or with LPS. IL-1 beta mRNA was expressed by C5a-treated PBMC, but very little or no IL-1 beta protein could be detected by ELISA or by Western blot analysis using a polyclonal Ab that reacts equally with pro-IL-1 beta and processed mature IL-1 beta. LPS-treated cells produced both IL-1 beta mRNA and protein. Velocity sedimentation analysis revealed, however, that IL-1 beta mRNA assembles into large polyribosomes in both C5a- and LPS-treated cells. Translation of the IL-1 beta mRNA in C5a-treated cells is not therefore blocked at the level of protein synthesis initiation. IL-1 beta mRNA was released from polyribosomes by treating the cells with puromycin, suggesting that the ribosomes are not frozen at the elongation phase of protein synthesis. One explanation for the data is that the rate of IL-1 beta polypeptide chain elongation or termination may be diminished in the C5a-stimulated PBMC. PMID- 8207243 TI - Gender differences in IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist secretion from mononuclear cells and urinary excretion. AB - Previous studies have reported increased secretion of IL-1-like activity from mononuclear cells and increased circulating levels during the luteal phase of the menstrual cycle. In this investigation, specific RIAs for the agonists IL-1 alpha and IL-beta as well as IL-1 receptor antagonist (IL-1Ra) were used to determine whether differential IL-1 secretory patterns exist between men and women or between phases of the menstrual cycle. Mononuclear cells were isolated from six men and five women at 4-h intervals from 8 am to 8 pm, with the women studied once in midfollicular phase and once in midluteal phase. In the absence of any intentional stimulation, significant differences in secretion were observed between groups (p < 0.03) for all three species of IL-1: women's cells isolated during the luteal phase secreted 5- to 10-fold more than cells from men, and women's cells isolated during the follicular phase secreted 13- to 28-fold more than cells from men. In addition, total 24-h urine samples were collected in intervals with end points coinciding with the blood samples. Urinary excretion correlated with cellular secretion for IL-beta and IL-1Ra (p = 0.024 and 0.028, respectively), indicating that the in vitro results may correspond to differential processes occurring in vivo. Although greater absolute amounts of each species of IL-1 were secreted during the follicular phase, the ratio of agonist to antagonist secreted was greater in the luteal phase (p < 0.05), in agreement with previous studies of bioactivity. These results indicate that the regulation of IL-1 secretion is fundamentally different in women compared with men and alludes to the possibility that IL-1 may serve different biologic functions in women than men. PMID- 8207244 TI - H-2D haplotype-linked expression and involvement of TNF-alpha in Th2 cell mediated tissue inflammation. AB - We recently reported that polyclonal anti-CD3 epsilon-pulsed Th2 cells mediate local tissue inflammation (DTH2) when injected into naive syngenic recipient mice, and that this response is entirely dependent on IL-4 in BALB/c (H-2d) mice. We now describe a different cytokine dependence in mice that bear a H-2b MHC haplotype. Injection of either soluble IL-4R (sIL-4R) or anti-TNF Ab partially inhibited swelling that was mediated by Th2 cells from high TNF-producing C57BL/6 mice. Anti-TNF and sIL-4R in combination were required to completely abrogate the swelling reaction and cellular infiltrate. Adoptive transfers across strain barriers showed that the TNF dependence was dictated by the origin of the transferred cells, rather than by the recipient. Experiments with intra-H-2 recombinant C57BL/10 strains indicated that TNF released by Th2 cells was correlated with the involvement of TNF in DTH2: Th2 cells from the H-2Db strains C57BL/10 and B10.A(2R) produced high amounts of bioactive TNF and mediated swelling that was partially inhibited by anti-TNF. In contrast, Th2 cells from B10.D2 and B10.A mice (H-2Dd) produced low levels of TNF, and anti-TNF had no effect on DTH2 in these strains. Our results suggest a linkage between the TNF dependence of DTH2, the capacity of Th2 cells to release TNF upon restimulation, and the donor H-2D haplotype; strain-dependent allelic expression of TNF seems to determine the involvement of this cytokine in DTH2. PMID- 8207245 TI - Transcriptional regulation of the TCA3 gene in mast cells after Fc epsilon RI cross-linking. AB - TCA3 is a pro-inflammatory cytokine expressed in mast cells after activation. To examine how this gene is regulated, TCA3 mRNA levels were examined and nuclear run-on experiments and promoter analysis were performed. Northern blot analysis showed that TCA3 message appeared in mast cells within 2 h after induction, with a t1/2 of 30 min. Nuclear run-on experiments revealed that the appearance of TCA3 mRNA occurred in large part because of an increase in the level of de novo transcription. Analysis of the promoter region demonstrated that inducible gene expression was directed by a region extending between 1.324 kb and 0.082 kb upstream from the transcription start site. There was a 60- to 80-fold induction with TCA3 CAT constructs extending between 1.324 kb and 0.324 kb upstream from the transcription start site after treatment with PMA/A23187 and a 30- to 40-fold induction with Fc epsilon RI cross-linking. There was a seven- to eightfold induction with the region extending between 0.136 kb and 0.082 kb upstream from the transcription start site. TCA3 CAT constructs containing regions encompassing either the 0.042 kb or 2.0 kb sequence from the transcription start site were not able to direct CAT-protein synthesis. The TCA3 5' flanking sequence contained negative regulatory activity. Electrophoretic mobility shift assays revealed that protein in nuclear extracts of activated mast cells bound to an NF-kappa B element of the TCA3 gene. These findings demonstrate that the TCA3 gene is regulated transcriptionally in mast cells, with minimal promoter sequences contained within the 0.082 kb upstream region of the TCA3 gene; a putative enhancer NF-kappa B element is contained between 0.324 kb and 0.136 kb and a putative inhibitory element is contained between 1.324 kb and 2.0 kb upstream from the transcription start site. PMID- 8207246 TI - TNF-alpha is a principal cytokine involved in the recruitment of NK cells to liver parenchyma. AB - Isolated murine splenic NK cells and the cultured murine endothelioma cell line, eEND2, were used to study the effects of cytokines on NK cell/endothelial cell adhesion. Treatment of eEND2 cells with TNF-alpha induced a marked increase (four to sevenfold) in adherence of NK cells, as compared with control cultures of endothelioma cells or eEND2 cells treated with IL-1 alpha or IL-6. TNF-alpha induction of NK cell adherence to eEND2 was dose dependent with rapid kinetics, reaching a maximum at concentrations between 10 and 1000 U/ml after a 2-h incubation. TNF-alpha treatment of L929 fibroblasts or CL-2 hepatoma cells did not result in increased NK cell adhesion. The concentration range of TNF-alpha that was found to maximally augment NK cell adhesion to eEND2 also induced NK cell chemokinetic activity. The relevance of these in vitro results was subsequently analyzed in vivo. Initial studies confirmed that a single dose of polyinosinic-polycytidylic acid and poly-L-lysine stabilized in carboxymethyl cellulose (poly-ICLC), augmented hepatic NK activity and resulted in a 2.2-fold increase in the number of liver-associated NK cells. Concomitant treatment of mice with a TNF-alpha neutralizing antisera eliminated both the hepatic influx of NK cells and the increase in poly-ICLC-induced liver NK activity. These results suggest that TNF-alpha is a principal cytokine involved in the in vivo recruitment and localization of parenchymal NK cells after treatment with a biological response modifier, and that this regulation seems to occur via alterations in NK cell/endothelial cell interactions. PMID- 8207247 TI - Superinduction of cytokine gene transcription by ciprofloxacin. AB - In addition to their antibacterial properties, certain antibiotics are also biologic response modifiers. The fluorinated 4-quinolone, ciprofloxacin, for example, up-regulates IL-2 and IFN-gamma production in PBLs stimulated in vitro. In the present study, ciprofloxacin was shown to increase the levels of mRNA for IL-1 alpha, IL-2 and its receptor, IFN-gamma, IL-3, IL-4, granulocyte macrophage/CSF, TNF-alpha, and lymphotoxin. As investigated with different T cell mitogens and alloantigens, the up-regulation of IL-2 production by ciprofloxacin was found to be independent of the mode of stimulation. Analysis of transcription activity showed that ciprofloxacin enhances IL-2 gene induction. The concentrations of nuclear factor of activated T cells (NF-AT-1) and AP-1 were also found to be increased by ciprofloxacin. Thus, ciprofloxacin interferes with a regulative pathway common to several cytokines. PMID- 8207248 TI - Functional platelet-activating factor receptors are expressed by monocytes and granulocytes but not by resting or activated T and B lymphocytes from normal individuals or patients with asthma. AB - Platelet-activating factor (PAF) may play a role in the regulation of immune responsiveness and is a potent mediator in asthmatic inflammation. However, as yet, the mechanisms whereby PAF mediates its pleiomorphic effects on immune cells have not been elucidated. Because PAF is a potent chemotactic factor for eosinophils, the presence of receptors for PAF (PAFR) on lymphocytes may provide a mechanism for the concurrent recruitment of both eosinophils and T lymphocytes into the airways of asthmatic patients. To address this issue, we have examined freshly isolated PBMC and granulocytic cells as well as various T and B lymphocyte lines with regards to PAFR expression and PAF-induced changes in intracellular calcium concentration. Using two-color immunofluorescence techniques and highly purified cell populations, it was not possible to detect surface PAFR protein or functional PAFR on resting and in vivo or in vitro activated T and B cells derived from nonallergic individuals or patients with allergic asthma. In addition, we were unable to detect PAFR mRNA, protein, or functional response to PAF in human or murine T cell lines. In contrast, we found functional PAFR in most B lymphoblastoid cell lines. Within the PBMC population, CD14+ cells respond to PAF. These results suggest that PAF does not interact directly with lymphocytes and thus that previous observations suggestive of such an interaction likely reflect the effects of PAF on monocytes. PAF-induced increases in intracellular calcium concentration were also detected in neutrophils and eosinophils, but were lower in granulocytes relative to the levels detected in monocytes. PMID- 8207249 TI - IL-1 down-regulates platelet-derived growth factor-alpha receptor gene expression at the transcriptional level in human osteoblastic cells. AB - Regulation of the platelet-derived growth factor (PDGF)-alpha receptor is thought to play an important role in pathophysiologic processes. Previously, we have reported that IL-1 has the potential to regulate PDGF-induced biologic activity in both normal human osteoblastic cells and the human osteoblastic cell line, MG 63, by decreasing the expression of PDGF-alpha receptor mRNA. In the present studies, we analyzed the effects of IL-1 on transcription rates and the stability of PDGF-alpha receptor mRNA in MG-63 cells. The data indicate that the t1/2 of PDGF-alpha receptor mRNA is approximately 3.3 h after incubation with the RNA II polymerase transcription inhibitor 5,6-dichloro-1 beta-D ribofuranosylbenzimidazole (DRB). Approximately the same t1/2 (3.1 h) was obtained when osteoblastic cells were incubated with IL-1. The t1/2 for PDGF alpha receptor mRNA for cells incubated with both IL-1 and DRB was 3 h. This finding suggests that the levels of PDGF-alpha receptor mRNA transcripts are not regulated by post-transcriptional mechanisms. Results of nuclear run-on analysis were consistent with this conclusion, demonstrating that IL-1 modulates PDGF alpha receptor gene expression at the transcriptional level. Surprisingly, incubation of cells with cycloheximide also caused down-regulation of PDGF-alpha receptor mRNA, which suggests that synthesis of a labile factor is necessary for constitutive expression. The functional consequence of down-regulation of PDGF alpha receptors by IL-1 was also assessed. By using chemotaxis assays, we demonstrated that IL-1 significantly inhibited PDGF-AA-mediated migration in human MG-63 osteoblastic sarcoma cells. PMID- 8207250 TI - Analysis of V beta 8-CDR3 sequences derived from central nervous system of Lewis rats with experimental autoimmune encephalomyelitis. AB - We have recently demonstrated that a strong bias for expression of V beta 8.2 is manifested early during the onset of experimental autoimmune encephalomyelitis (EAE) induced by guinea pig basic protein (Gp-BP) immunization of Lewis rats. More importantly, the V beta 8.2 bias was observed in T cells infiltrating the spinal cord (SC) and in cerebrospinal fluid (CSF), but was not present in T cells isolated from the periphery. Here, we report the V beta 8-CDR3 sequences found in unselected SC, CSF, and lymph node (LN) T cell populations at onset of Gp-BP induced EAE. Striking similarities were observed among sequences derived from SC and CSF. Evidence for oligoclonal expansion of V beta 8.2 sequences associated with previously characterized encephalitogenic clones was observed in both SC and CSF, but not in LN. An AspSer CDR3 motif identified in encephalitogenic clones recognizing the dominant 72-89 epitope of Gp-BP was found in 9/22 SC cDNA clones, 11/24 CSF cDNA clones, and 1/16 LN cDNA clones. Interestingly, J beta 2.7 and J beta 1.3 were also highly represented in SC and CSF, but not in LN. Given that these sequences were derived from T cells present at the site of autoimmune attack and not selected by in vitro manipulation, the data offer compelling evidence that 1) selective recruitment and/or expansion of V beta 8.2+ T cells are occurring in the central nervous system; 2) these events are at least partially dependent on V beta residues which are likely to influence Ag binding; and 3) CSF-derived T cells provide a representative view of CNS events at the onset of EAE. PMID- 8207251 TI - Characterization of peripheral autoregulatory mechanisms that prevent development of cyclosporin-induced syngeneic graft-versus-host disease. AB - Administration of cyclosporin after syngeneic bone marrow transplantation paradoxically elicits a T lymphocyte-dependent autoaggression syndrome termed syngeneic graft-vs-host disease (SGVHD). The induction of SGVHD requires two essential components, the emergence of autoreactive lymphocytes from the thymus and the elimination of a T cell-dependent peripheral autoregulatory mechanism. These studies used the SGVHD model to further characterize this regulatory system that modifies the autoimmune potential of autoreactive effector cells. Our studies reveal that although cyclosporin did not interfere with the effector function of the autoregulatory T cells, it prevented the reconstitution of the regulatory system after syngeneic bone marrow transplantation. Furthermore, the autoregulation of SGVHD is a dynamic process specifically recognizing and responding to the autoreactive SGVHD effector cells. Challenge or priming of normal Lewis rats by intravenous infusion of irradiated SGVHD effector cells activates and amplifies this autoregulatory system resulting in: 1) a threefold enhancement of autoregulatory T cell function, 2) the appearance of a dominant autoregulatory T cell population belonging to the CD4+ T helper lymphocyte subset, and 3) the capacity of irradiated primed autoregulatory T cells to inactivate SGVHD effector lymphocytes in vitro. Additional studies reveal that effective autoregulation required a specific interaction of the TCR-alpha/beta on the autoregulatory cells with the MHC class II determinants on the autoreactive lymphocytes. PMID- 8207252 TI - CTL responses to the gag polyprotein encoded by the murine AIDS defective retrovirus are strain dependent. AB - Murine AIDS (MAIDS) is induced by a mixture of retroviruses, of which a replication defective virus is the proximal agent of disease. This defective virus harbors a single intact gene that encodes an aberrant gag polyprotein. Certain mouse strains are genetically resistant to MAIDS, with several genes, including H-2Dd, contributing to this resistance. Because MHC class I gene products present intracellular Ags to CTL, recombinant viruses were used to determine whether gag-specific CTLs mediate the genetic linkage between H-2Dd and resistance. Interestingly, while genetically resistant BALB/cByJ and C57BL/KsJ mice (H-2d) generated gag-specific CD8+ CTLs, a similar response was not detected in susceptible BALB.B and C57BL/6J mice (H-2b). However, this CTL response does not appear to be responsible for genetic resistance because: 1) a vigorous CTL response could also be generated by susceptible (C57BL/6 x BALB/cBy) F1 mice and 2) the relevant epitope is H-2Kd restricted. PMID- 8207253 TI - Arrested rearrangement of TCR V beta genes in thymocytes from children with X linked severe combined immunodeficiency disease. AB - Human X-linked severe combined immunodeficiency disease (SCID) is an immunodeficiency disorder in which T cell development is arrested in the thymic cortex. B lymphocytes in children with X-linked SCID seem to differentiate normally. X-linked SCID is associated with a mutation in the gene that encodes the IL-2R gamma-chain. Because TCR-beta gene recombination is a pivotal initial event in T lymphocyte ontogeny within the thymus, we hypothesized that a failure to express normal IL-2R gamma could lead to impaired TCR-beta gene recombination in early thymic development. PCR was used to determine the status of TCR-beta gene-segment rearrangements in thymic DNA that had been obtained from children with X-linked SCID. The initial step in TCR-beta gene rearrangement, that of D beta to J beta recombination, was readily detected in all thymus samples from children with X-linked SCID; in contrast, V beta to DJ beta gene rearrangements were undetectable in the same samples. Both D beta to J beta and V beta to DJ beta TCR genes were rearranged in the thymic tissues obtained from immunologically normal children. We conclude that TCR beta-chain gene rearrangement is arrested in children with X-linked SCID. Our results suggest a causative relationship between the failure of TCR beta-chain gene rearrangements to proceed beyond DJ beta rearrangements and the production of a nonfunctional IL 2R gamma-chain. PMID- 8207254 TI - A potential role for antigen selection in the clonal evolution of Burkitt's lymphoma. AB - Burkitt's lymphoma (BL) is a monoclonal lymphoproliferative disorder characterized by the presence of specific chromosomal translocations that involve the c-myc proto-oncogene. Two subtypes of BL exist (endemic and sporadic) that differ in the prevalence of EBV genome expression. Although EBV infection may promote cellular proliferation in endemic BL, little is known about the forces that drive clonal expansion and evolution in the majority of EBV-negative sporadic BL. This study on an EBV-negative sporadic BL cell line derived from an AIDS patient provides evidence that antigenic stimulation may play a role in the development and/or expansion of such tumors. This cell line (BRG-P) contained a series of cellular clones that elaborated both IgM and IgA. Southern blot analyses of the line and its sublines indicated that both the IgM+ and IgA+ cells had identical c-myc and Ig JH gene rearrangements, indicating that they were derived from a common precursor, some of which eventually underwent an isotype switch. Ig VH gene sequence analyses of 21 molecular clones derived from the parental BRG BL line and two of its sublines demonstrated that all the clones used the same VH3 gene. Five unique intraclonal variants were identified at four distinct nucleotide positions (125, 161, 355, 375), which undoubtedly represented somatic mutations. Four of these five mutations occurred within complementary determining regions; all resulted in amino acid replacements. Moreover, an identical G to A nucleotide substitution that resulted in an identical amino acid change occurred at two distinct points in clonal evolution that were separated by the isotype class switch. Thus, the locations and types of the VH gene mutations, together with the occurrence of an isotype switch, are highly suggestive of an ongoing role for Ag stimulation and selection in the evolution of the malignant clone. PMID- 8207255 TI - Production, selection, and maturation of thymocytes with high surface density of TCR. AB - The main steps in intrathymic T cell differentiation have been defined using bromodeoxyuridine as a postmitotic cell tracer. Thymocytes with a high surface expression of the TCR are generated in the first 24 h after DNA synthesis. The phenotype of these TCR(high) cells was studied during 10 days by using pairs of surface markers associated with BrdUrd. During the first 2 days, TCR(high) cells were of the CD4+CD8+HSA(high) phenotype, transiently expressed the early activation marker CD69, and contained a high percentage of cycling cells. This activation step preceded the transition from CD4+CD8+ to CD4+CD8- and then to CD4 CD8+ cells, followed by progressive HSA down regulation and increase in the expression of H-2K, Qa-2, and CD45RB. The phenotypic maturation was completed in 9 days. In Mls-1a mice, negative selection of V beta 6+ cells was observed at the earliest step of TCR(high) cell generation, and positive selection of V beta 8.2+ and V beta 14+ cells took place later and was correlated to the activation step. These data suggest that high TCR expression and cell activation are necessary for positive selection and subsequent T cell maturation. PMID- 8207256 TI - Evidence for protein tyrosine kinase involvement in ligand-induced TCR/CD3 internalization and surface redistribution. AB - Triggering of the TCR/CD3 complex can lead to its internalization and modulation from the cell surface. In the present study, we address the question of the dependence of internalization on protein tyrosine kinase (PTK) activation. With use of an activating anti-clonotypic (anti-Ti) mAb on a CTL clone, we have shown that the PTK inhibitors genistein and tyrphostin 25 delayed anti-Ti-induced internalization, but did not affect fluid phase protein uptake or transferrin receptor cycling. Confocal microscopy with use of fluorescent anti-Ti mAb revealed that the inhibition of TCR internalization corresponded to the induction of large patches that were localized in cell membrane areas depleted of polymerized actin, the formation of which was dependent on the combined action of the anti-Ti mAb and the PTK inhibitors. In contrast to the effect of these PTK inhibitors, depletion of Src-like PTKs by T cell pretreatment with herbimycin A led to an increased rate of anti-Ti-induced internalization. Internalization induced by the monovalent Fab fraction of anti-Ti mAb was similarly affected by the PTK inhibitors, although the extent of induced internalization was less by approximately one-half. An analysis of substrates phosphorylated in kinase assays on TCR/CD3 immunoprecipitates of the CTL, which were activated by anti-Ti mAb in both the absence and presence of genistein, identified protein bands in which phosphorylation or association with CD3 was inhibited in the presence of genistein. Thus, a genistein-sensitive PTK activity seems to control ligand induced TCR/CD3 complex redistribution and internalization. PMID- 8207257 TI - Modulation of fibronectin and thymic stromal cell-dependent thymocyte maturation by retinoic acid. AB - Retinoic acid (RA) controls the differentiation of a variety of cell types, although its role in influencing T cell development and the mechanisms potentially involved have not been thoroughly investigated. To study the ability of RA to modulate T cell development, we established a thymic stromal cell line (TC-1S) that supports the phenotypic maturation of CD4-8- double negative (DN) or CD3-4-8- triple negative (TN) thymocyte precursors. Cocultures of either DN or TN thymocytes on a monolayer of TC-1S cells resulted in the appearance of thymocytes with a more mature phenotype (CD4+8+ double positive, CD4+ or CD8+ single positive, and CD3(low) cells). Double negative T cell contact with TC-1S cells also increased the production of fibronectin (FN) by the thymic stroma and the expression of the VLA-4 FN receptor on the DN cells. Ab-mediated inhibition of the interaction between FN and its receptors significantly reduced the level of induced T cell maturation. Addition of RA either to TC-1S cells alone or to the coculture with DN cells decreased stromal cell FN expression, antagonized DN cell induced increase in stromal cell FN production and significantly inhibited in vitro thymocyte maturation. The effects of RA were likely mediated by RA acid receptors alpha and gamma expressed both in DN thymocytes and TC-1S cells. Together these data suggest that FN/VLA-4 interaction may be an important component of stromal cell-dependent thymocyte phenotypic differentiation and that this interaction can be one of the targets for the influence of RA in T cell development. PMID- 8207258 TI - Rapid quantitation of apoptosis in pure and heterogeneous cell populations using flow cytometry. PMID- 8207259 TI - Quantitation of Fc gamma RII mRNA in platelets and megakaryoblastic cell lines by a new method of in situ hybridization. AB - We have developed a highly sensitive and quantitative, non-isotopic method of in situ hybridization in which the level of probe binding to intracellular mRNA is determined using an ELISA based detection method. Highly purified cell preparations or cells from a cultured cell line are centrifuged into 96 well microtiter plates. The cells are fixed with formalin and pre-treated with Triton X-100 and Nonidet P40 before photobiotin labeled cDNA probes are applied. The biotin from the hybridization is detected using multiple applications of streptavidin and biotinylated alkaline phosphatase and then visualized by the p NPP (p-nitrophenyl phosphate) conversion method. We have determined a number of the optimal parameters in the procedure including the effects of cell numbers per well, development times and standardization of data using ubiquitous beta-actin mRNA and poly-A+ RNA expression as controls. We have used the technique to study the level of expression of FcgR mRNA in platelets and precursors. We found that platelets and megakaryoblastic cell lines only express mRNA for Fc gamma RII. The presence of the Fc gamma RII molecules was confirmed by complementary studies using immunohistochemistry with specific monoclonal antibodies IV.3 and KB61. PMID- 8207260 TI - Use of fluorescent dyes in the determination of adherence of human leucocytes to endothelial cells and the effect of fluorochromes on cellular function. AB - A number of supravital fluorochromes are available to study leucocyte functions in vitro and in vivo. The fluorescein ester most widely used, fluorescein diacetate, has the disadvantage of rapid cellular efflux, whereas more recently developed fluorescent probes do not exhibit this inconvenient trait. However, their effect on cellular functions has not been thoroughly investigated in humans. In this study, we describe a simple and rapid fluorometric method for measuring cell adhesion to endothelium, comparing 5 different fluorochromes. Furthermore, we evaluated the effect of fluorescent dye labelling (with CFDA, CFSE, BCECF-AM, calcein-AM or DiI), on various cell functions, including, apart from adhesion, lymphocyte proliferation, granulocyte chemotaxis and superoxide production. calcein-AM and DiI proved to be the fluorochromes with the least effect on cellular function. BCECF-AM did not interfere with lymphocyte proliferation, but exhibited some influence on superoxide production and chemotaxis of granulocytes. CFDA showed a detrimental effect on both lymphocyte and granulocyte functions whereas CFSE gave intermediate results. In the adhesion assay, calcein-AM, CFSE and DiI performed comparably well. Since labelling with C12-DiI was homogeneous, this probe was also appropriate for the adhesion test, although somewhat higher background staining was present. We conclude that the fluorochromes are powerful tools when analysing the adhesion of human leucocytes to endothelial cells. However, since fluorochrome labelling can interfere with other cellular functions, the fluorescent probe has to be carefully chosen with regard to the cell type and function to be studied. PMID- 8207261 TI - Monoclonal antibodies directed against surface and intracellular antigens of mouse granulated metrial gland cells. AB - Rat monoclonal antibodies with reactivity directed against mouse GMG cells have been produced. One of the antibodies (GMG-1) reacts with a surface antigen of GMG cells and cross-reacts with T lymphocytes. Another (GMG-2) reacts with an intracellular antigen in GMG cells and with asialo-GM1 positive cells in the spleen. Three antibodies (GMG-3, -4, -5) bind to intracellular antigens in GMG cells. The cross-reactivity of these antibodies is discussed with reference to the lineage relationship of GMG cells to NK cells and T cells and the recent suggestion that NK cells and T cells have a common progenitor cell. It is proposed that GMG cells share this common progenitor cell but are otherwise independent of the NK or T cell lineages. PMID- 8207262 TI - Induction of collagen-induced arthritis in mice using a non-ulcerative adjuvant. PMID- 8207264 TI - A fluorescence microassay for the quantitation of integrin-mediated adhesion of neutrophil. AB - The avidity of leukocyte integrin CR3 (Mac-1, CD11b/CD18, alpha m beta 2) on neutrophils (PMN) may be rapidly modulated by several agonists. We describe a method for determining the avidity of these receptors by measuring the adhesion of PMN to fibrinogen-coated surfaces. Cells are loaded with a succinimidyl ester of carboxyfluorescein diacetate, which is deacetylated by intracellular esterases yielding a highly fluorescent carboxyfluorescein that remains trapped within the PMN. The number of cells adhering to fibrinogen-coated wells of Terasaki microplates is quantitated with a fluorescence plate reader. Stimulation of PMN with a number of agonists, including PMA, fNLLP, Ca-ionophore A23187, interleukin 8, tumor necrosis factor and lipopolysaccharide strongly increased adhesion to fibrinogen, which was CD11b/CD18 dependent. The extent of cell adhesion depended on stimulus concentration and incubation time. This assay requires little time, utilizes small numbers of cells and does not require hazardous reagents. PMID- 8207263 TI - Application of a flow cytometric method using autofluorescence and a tandem fluorescent dye to analyze human alveolar macrophage surface markers. AB - Human resident alveolar macrophages (AM) exhibit autofluorescence when excited by light from 488 nm lasers used by most flow cytometers. Because this autofluorescence occurs at peak 540 nm, it obscures fluorescence generated by commonly used immunofluorescent reagents (e.g., antibodies conjugated to fluorescein isothiocyanate (FITC) or R-phycoerythrin (R-PE)) applied for cell surface marker analysis. Therefore, a two color flow cytometric method has been developed that permits the quantitative phenotypic analysis of AM without influence by their natural autofluorescence. In this method, a commercially available preparation of secondary polyclonal antibodies (recognizing primary specific mouse IgG monoclonal antibodies) that are conjugated to a tandem fluorochrome dye (containing R-PE and Cy5) is used. Using this method, the expression of 12 different surface markers on AM obtained from bronchoalveolar lavage (BAL) of 13 subjects was analyzed and compared with their expression on the surface of peripheral blood monocytes. This method will facilitate analysis of surface markers on AM in a variety of disorders. PMID- 8207265 TI - Semi-preparative purification and validation of monoclonal antibodies for immunotherapy in mice. AB - A number of rat hybridomas were adapted to grow in RPMI containing either 5% IgG depleted FCS or 1% serum-free Nutridoma. Alternatively, protein-free Ultradoma PF was used. Growth in these media allowed purification procedures to be used that are based on tangential ultrafiltration in combination with affinity chromatography on gels linked to protein G or anti-rat L chain coupled antibodies. The isolated antibody preparations were found to be pure and to consist of monomeric intact IgG. The yield and recovery of mAb using this procedure were found to be consistently high. These antibody preparations were analyzed for endotoxin contamination. Whereas during isolation endotoxin contamination increased, the endotoxin content per mg purified protein did not. Affinity chromatography on Detoxi-gel resulted in the efficient removal of this contamination and using this protocol the antibody preparations obtained were found to be of sufficient purity, activity and low endotoxin content to permit their in vivo use in animal models of immunotherapy. PMID- 8207266 TI - Multiparameter flow cytometric analysis of inflammatory cells contained in bronchoalveolar lavage fluid. AB - Quantitative analysis of surface molecule expression on viable alveolar macrophages (AM) by use of flow cytometry is hampered by non-specific antibody binding to various AM FcIgG receptors as well as extensive and heterogeneous autofluorescence of this cell type. The following approaches were undertaken to circumvent these obstacles. FcIgG receptors were blocked by excess human immunoglobulin. The use of a long wave-emitting dye (phycoerythrin/cyanine-5 tandem conjugate) permitted avoidance of the peak (green) AM autofluorescence range. Moreover, a cell-by-cell compensation for the remaining red autofluorescence background was employed. This was based on two facts: (i) strict correlation between green (F488/530) and red autofluorescence (F488/660) for all AM populations investigated; and (ii) neglectable overlap of the antibody associated red fluorescence into the 530 nm autofluorescence detection wavelength. A fraction of the green autofluorescence (F488/530; channel 1) was then subtracted from the red fluorescence (F488/660; channel 2) on a cell-by-cell basis using standard two colour fluorescence compensation circuits. The validity of this FACS technique was confirmed by comparison with immunocytochemical staining and a reverse rosetting method. On AM lavaged from carcinoma-bearing but otherwise disease-free human lungs, the pattern of surface antigen expression was assessed with a panel of monoclonal antibodies. When applying to complex mixtures of bronchoalveolar lavage cells, the autofluorescence was employed to separate AM from granulocytes and lymphocytes. In conclusion, the presently described FACS technique allows quantitative immunostaining of surface molecules on AM, even when present in low copy numbers on highly autofluorescent cells originating from smokers. PMID- 8207267 TI - Antibody secreting cells as specific probes for antigen identification. AB - Parasite specific antibody probes were prepared by harvesting lymphocytes from infected tissue and incubating them in vitro to allow the spontaneous secretion of antibodies in the culture medium by antibody secreting B cells present in the lymphocyte cultures. The culture supernatant was then used to screen Western blots of parasite antigens and resulted in the detection of antigens specific for the parasite stages present in the tissue at the time of sampling. Similar antigen recognition patterns were also observed when the cells were taken from the draining lymph nodes but the same pattern was not observed with serum taken from the same animal. The use of antibody probes obtained from in vivo induced antibody secreting B cells (ASC probes) offers a unique and universal approach to study local antibody recognition during infection. PMID- 8207268 TI - Flow cytometric detection of anti-neutrophil cytoplasmic autoantibodies. AB - An intracytoplasmic immunofluorescence staining technique which allows the detection and quantification of anti-neutrophil cytoplasmic autoantibodies (ANCA) by flow cytometry is described. A polymorph neutrophil population from human peripheral blood was used in this study as indicator cells. These were fixed and permeabilized by paraformaldehyde, Tween 20 and saponin, to allow ANCA in the patients sera to reach their intracellular antigen targets. The numbers of indicator cells remained unaltered by the permeabilization protocol and no cell aggregation or loss of intracellular antigenicity was observed. An excellent agreement (91% (207/228)) between ANCA detection by immunofluorescence microscopy (IF) and flow cytometry was noted. Compared with IF assay, the flow cytometric method has a sensitivity of 93% (42/45) and a specificity of 90% (165/183). Although not able to discriminate between P-ANCA or C-ANCA, this flow cytometric method has the advantage of providing an objective, reproducible and quantitative measure of ANCA, which makes it an ideal technique for screening of patients sera for ANCA reactivities. PMID- 8207269 TI - Analysis of the V beta specificity of superantigen activation with a rapid and sensitive method using RT PCR and an automatic DNA analyser. AB - Polymerase chain reaction (PCR) by the specific amplification of a DNA target sequence has been shown to permit analysis of T cell receptor usage. The complete repertoire is amplified using oligonucleotide primers specific for each of the known V alpha or V beta regions of the T cell receptor. One of the methods currently used to appreciate the relative quantity of different V chains of the TCR is by coamplifying in the same reaction tube the variable region of one chain together with the constant region of the other chain. We have optimised PCR conditions and analysed PCR products on an automatic DNA analyser facilitating the quantification of the amplified products, avoiding the use of radioisotopes, and allowing the determination of the sizes of CDR3 regions, thus giving new information on the modification of the T cell repertoire. This method was used to analyse the precise V beta specificity of the T cell activation with the superantigen SEB. PMID- 8207270 TI - Management of patients with HIV/AIDS: need for comprehensive care. PMID- 8207271 TI - Women and AIDS. PMID- 8207273 TI - Campaigning against AIDS. PMID- 8207272 TI - AIDS and the gateway of the body. PMID- 8207274 TI - Laboratory diagnosis of HIV infection. PMID- 8207275 TI - Blood safety and rational use of blood. PMID- 8207276 TI - Opportunistic infection in AIDS. PMID- 8207277 TI - Vaccines for control of HIV infections. PMID- 8207278 TI - AIDS-case surveillance. PMID- 8207279 TI - Current status of AIDS and HIV infection in India. PMID- 8207280 TI - HIV infection and health care worker. PMID- 8207281 TI - HIV infection control in health care settings. PMID- 8207282 TI - Safe sex. PMID- 8207283 TI - Strategies for prevention and control of HIV infection/AIDS in the country. PMID- 8207284 TI - Sexually transmitted diseases and HIV infection: implications for control and prevention. PMID- 8207285 TI - [Determination of neutrophil function in respiratory infection by chemiluminescence (CL). II: Changes in neutrophil's CL by chemotherapy against chronic lower tract infection]. AB - Neutrophil's CL (CL-index) in were assayed in 18 patients with chronic lower tract infection (13 cases in the exacerbated phase and five cases in the stable phase) three times per case: before, during and after chemotherapy. Before the initiation of chemotherapy, the CL-index.N (neutrophil numbers x CL-index) in patients with exacerbation remained higher than in those without exacerbation. At the exacerbated phase, the CL-index of nine patients and the CL-index.N of 10 patients fell lower than those obtained before treatment. AT the stable phase, the CL-index and the CL-index.N did not change remarkably during and after chemotherapy. PMID- 8207286 TI - [Serotype-specific amplification of Rickettsia tsutsugamushi DNA from clinical specimens by nested polymerase chain reaction]. AB - Polymerase chain reaction (PCR) with nested primer pairs was used to diagnose Tsutsugamushi disease and identify the Rickettsia tsutsugamushi serotype. The primer pairs used for PCR were designed on the basis of the nucleotide sequence of the gene that encodes the 56-kDa antigen. Five serovariants, the Gilliam, Karp, Kato, Kawasaki, and Kuroki strains of Rickettsia tsutsugamushi were detected and identified by nested PCR. The serotypes of patients registered during 1990 to 1992 in Kanagawa Prefecture were identified by nested PCR. Sixty percentage of patients showed Kawasaki types, 20% Karp types, and 20% Kuroki types. This result suggested that the recent Tsutsugamushi disease were mostly caused by Kawasaki types in Kanagawa Prefecture. PMID- 8207287 TI - [Application of urine sediment for diagnosis of gonococcal urethritis by enzyme immunoassay]. AB - We evaluated the usefulness of urine sediment from male gonorrhea patients for detecting gonococcal antigens by enzyme immunoassay, Gonozyme (Abbott Laboratories). Experiments for dilution rate of urine sediment with buffer provided in a kit indicated that dilution of sediment at 1:4-6 would be practical in performing Gonozyme. All urine sediment specimens from 18 gonorrhea patients showed positive by Gonozyme, and 68, except for 3, culture-negative control urine sediments, including 8 sediments from patients with chlamydial urethlitis, were negative. Based on comparing results of Gonozyme with those of culture, sensitivities and specificity were 88.9-100% and 95.6%, respectively. During storage of urine sediment at 5 degrees C for 7 days, absorbance values were stable. Therefore, urine sediment could be preserved or transported. We conclude that urine sediment is useful for diagnosis of gonococcal urethritis in males by Gonozyme. PMID- 8207288 TI - [Fungal infection in hepatobiliary and pancreatic diseases: clinical evaluation in autopsy cases]. AB - A clinical assessment of fungal infection in hepatobiliary and pancreatic diseases during 1975 and 1991 was made and 25 cases of systemic mycosis were noted. Among 25 cases there were 20 liver diseases (hepatocellular carcinoma 12, liver cirrhosis 5, fulminant hepatitis 2, polyarteritis nodosa 1), 2 cases of gallbladder cancer and 3 cases of pancreatic cancer. The fungus was consisted of 14 cases (56%) of Candida, 9 cases of Aspergillus (36%), and 2 cases of Cryptococcus (8%). Fungal infection was most frequent in the lung (8 cases) and esophagus (6 cases), but rarely in the stomach, lymph node, liver, thyroid, kidney and gallbladder. Generalized fungus infection was noted in four cases (16%). Fatal fungal infection was complicated in liver cirrhosis (2 cases), fulminant hepatitis (one case), gallbladder cancer (one case) and cystadenocarcinoma of the pancreas (one case). In five fatal cases three cases of Aspergillus pneumonia and two cases of Candida septicemia were included. Glucocorticoid was used in 13 cases (52%) and anti-cancer drugs was administered in two cases (12%). However, in 9 cases (36%) without treatment of glucocorticoid or anti-cancer drug fungal infection was detected. In conclusion, there is a possibility of fungal infection in grave hepatic diseases and empirical administration of anti-fungal agent may be necessary. PMID- 8207289 TI - [Clinical significance of positive blood cultures in the Nagasaki Rosai Hospital during the past 6 years]. AB - In this clinical study we tried to find out the clinical significance of positive blood cultures between Jan. 1984 and Dec. 1989 in the Nagasaki Rosai Hospital. In this period the association between the isolated bacteria from blood cultures (398 specimens: 17.9%) and clinical background were evaluated. Each year the positive cultures were seen in about 18-20%. The distribution of bacteria showed increase percentage of the gram-positive organisms such as coagulase-negative Staphylococcus. Gram-negative organisms in included P. aeruginosa, A. calcoaceticus and E. coli. A. calcoaceticus was frequently found from the dept. of neurosurgery. Fungus, mostly Candida, was isolated in about 10-20%. The specimens were provided from department of internal medicine (62.9%) and neurosurgery (22.8%). An analysis of 213 episodes of 188 bacteremic cases was made. The onset of bacteremia had two peaks, 24 h or 1 month, after admission. The primary infected sites were the urinary tract (26.7%), respiratory system (14.5%) and central nervous system (6.1%). The central venous catheter was an important infected site. The major underlying diseases included acute cerebrovascular diseases, cardiac failure due to valvular heart diseases or acute myocardial infarction and/or iatrogenic immunocompromised state. The major complications were disseminated intravascular coagulation (DIC) (24.4%) and multiple organ failure (MOF) (8.9%). Half of the DIC episodes was caused by gram positive cocci such as CNS, E. faecalis and MRSA. 68.4% of MOF episodes was associated with gram-negative bacteria. While the remainder was caused by gram positive cocci including CNS and MRSA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207290 TI - Status of soil-transmitted helminthic infection in Nepal. AB - A retrospective evaluation of the status of soil-transmitted helminthic infection in Nepal during the period from 1985 to 1992 was conducted at the Parasitology Laboratory, Department of Pathology, TU Teaching Hospital in Kathmandu. An average of 6,537 faecal samples were examined each year for the presence of various types of intestinal parasites. The annual rate of positivity of these samples for soil-transmitted helminthiasis ranged from 18.0 to 36.6%. The annual incidence decreased every successive calendar year in both adults and children, irrespective of sex. Among the various types of helminths, the most common was Ascaris lumbricoides (roundworm), followed by hookworm. The incidence of A. lumbricoides remained constant throughout the study period, while that of other parasites markedly decreased each year. PMID- 8207291 TI - [Anaerobic respiratory infection--evaluation of methods of obtaining specimens]. AB - Anaerobic cultures were performed on various kinds of specimens obtained from 67 patients with respiratory infections. The infections consisted of 33 cases of pneumonia, 14 cases of lung abscess, 6 cases of pyothorax, 9 cases of chronic lower respiratory tract infection, and 5 cases of infection of pulmonary cyst. Specimens included bronchoscopic specimens obtained using a single tube or protected catheter brush (PCB), transtracheal aspirate, percutaneous lung aspirate, aspirate using a suction tube through the tracheostomy or intubation tube, and pleural fluid. Anaerobes were isolated in 80% of pyothorax, 43% of lung abscess, and 15% of pneumonia (42% of aspiration pneumonia), respectively. Anaerobes isolated frequently in respiratory infections included Prevotella spp., Fusobacterium spp., and Peptostreptococcus spp. In regard to the type of specimen, bronchial aspirate obtained by bronchoscopy was useful in examination of pneumonia, and was useful as percutaneous lung aspirate in examination of lung abscess. But there was discrepancy of culture results between specimens obtained by different methods in the same patient. To confirm anaerobes as pathogens in respiratory infections, it is necessary to select an appropriate method to obtain specimens and to interpret the culture results comprehensively. PMID- 8207292 TI - [Fundamental and clinical studies on MIC breakpoint of SY5555 for Enterococcus faecalis in complicated urinary tract infections of moderate severity]. AB - A multicenter clinical study was carried out to investigate the clinical efficacy of SY5555 from viewpoint of its MIC breakpoint for Enterococcus faecalis. SY5555 was administered in dosages of 150 mg x 3/day and 300 mg x 3/day, for 7 days, to patients with complicated urinary tract infections of moderate severity (no indwelling catheter). Based primarily on the bacteriological efficacy (eradication) as the criterion for evaluation, the MIC breakpoint of SY5555 was investigated. SY5555 showed potent antimicrobial activity towards E. faecalis, and its MIC80 value for the clinical isolates of this bacterial species was 1.56 micrograms/ml. Analysis was carried out to determine the extent to which this in vitro activity is corroborated by the drug's clinical efficacy in eradicating E. faecalis. 1. Experimental study In a study employing an experimental model of complicated bladder infections of moderate severity, it was judged that the MIC breakpoints of SY5555 administered at 150 mg x 3/day and 300 mg x 3/day were 2 micrograms/ml and 8 micrograms/ml. 2. Clinical study SY5555 was administered at 150 mg x 3/day (7 days) to six patients and at 300 mg x 3/day (7 days) to 32 patients, and the clinical efficacy of these treatments was investigated. 2.1. Investigation of the clinical MIC breakpoint showed it to be 12.5 micrograms/ml for both the 150 mg x 3/day and 300 mg x 3/day regimens. However, since the number of cases in this study was small, analysis was performed of the data from a large number of cases by including the cases registered in a nation-wide Phase II study of SY5555. That analysis showed the clinical MIC breakpoint for the two dosages to be 3.13 micrograms/ml and 6.25 micrograms/ml. Thus, this analysis of large number of cases yielded clinical MIC breakpoint that are in agreement with the abovementioned experimental MIC breakpoints. 2.2. In the evaluation of the efficacy rate using the UTI drug efficacy evaluation criteria, cases rated as "good" or "excellent" numbered five of the six patients in the 150 mg x 3/day treatment group and 25 of the 32 (78.1%) patients in the 300 mg x 3/day treatment group, or 30/33 (78.9%) cases overall. These efficacy rates are about the same as the 82.0% reported for the nation-wide Phase II study. 2.3. Each of the strains of E. faecalis isolated from the patients was found to be eradicated by the SY5555 treatment: four strains in the 150 mg dosage group (the MIC of each was 3.13 micrograms/ml or less) and 18 strains in the 300 mg dosage group (the MIC of each was 6.25 micrograms/ml or less). Moreover, in both dosage groups, E. faecalis was not found to recur after the SY5555 treatment. 3. Conclusions In consideration of the above findings in the investigations of treatment of patients with complicated urinary tract infections of moderate severity, the following conclusions can be drawn. 3.1. In antimicrobial treatment employing SY5555 in a regimen consisting of 300 mg x 3/day for 7 days, the clinical breakpoint is in the range of 6.25-12.5 micrograms/ml. 3.2. In particular, as would be surmised from the fact that the MIC80 value of SY5555 for E. faecalis isolated is 1.56 micrograms/ml, this drug shows quite strong efficacy in the eradication of E. faecalis from cases of complicated urinary tract infection. PMID- 8207293 TI - [Correlation between echo type 6 viruses replication in RD-18S cells and pathogenesis]. PMID- 8207294 TI - [An epidemiological study of group A, B, C, and G hemolytic streptococci isolated from elementary school children in the recent 12 years. Part I. Isolation trends. Streptococcal Diseases Study Group]. AB - During a 12-years period between September, 1980 and November, 1992, hemolytic streptococci (group A, B, C, & G) in throats of healthy school children in Osaka were examined every other month. The results were summarized as follows. 1. 5,023 strains of hemolytic streptococci were detected from 11,647 specimens, 43.1%. Among them, 2,395 strains (20.6%) belonged to group A, 1,647 (14.4%) to group B, 767 (6.6%) to group G and 187 (1.6%) to group C. 2. In the first half of the research, group A streptococci were detected predominantly and the last half, group B generally. Both this lower rate of group A to the total strains (47.7%) and this higher rate of group B (33.3%) were due to the small number of lower school grade children from whom group A streptococci are often detected and also due to application of the selective enrichment medium. 3. Group A streptococci were classified T-type. The most common serotype was T-1, and 638 strains (26.6%) were detected, followed by T-12, 377 (15.7%), T-6, 210 (8.8%) and T-13, 203 (8.5%). The dominant serotype was exchanged annually, but only T-1 was the most common serotype for 4 years (1983-1986). 4. In group B, the most common serotype was Ia, and 524 strains (31.3%) were detected, followed by III, 417 (24.9%), Ib, 164 (9.8%), III/R, 130 (7.8%) and Ia/c 122 (7.3%). Annual changes of serotype were as follows; Ia was dominant from 1980 to 1988, III from 1989 to 1990 and NT6 in 1991-1992 generally. PMID- 8207295 TI - [An epidemiological study of group A, B, C and G hemolytic streptococci isolated from elementary school children in the recent 12 years. Part II. Susceptibility to antibiotics. Streptococcal Diseases Study Group]. AB - During a 12-years period between 1980 and 1992, 5,023 strains of hemolytic streptococci were detected from throats of school children, and described in part I. Among them, the following strains their susceptibility were tested to 14 kinds of antibiotics; 1,511 strains of group A, 1,038 of group B, 125 of group C, 553 of group G. 1. No resistant strains against both penicillins (PCG, AMPC, ABPC, ACPC) and cephems (CER, CET, CCL, CEX) could be found. Strains of group B were less susceptible than the others to penicillins and cephems. 2. Some resistant strains were found against macrolides (EM, OL & JM), 5.9-8.6%. These resistant strains belonged many to group A and a few to group B & G. Since 1983, the gradual decrease of the resistant strains was noted though few were found after 1986. 3. To TC a number of resistant strains were detected in group A, B, C & G through this study, (12.5-48.4%). 4. To CP some resistant strains were found from 1980 to 1985 among group A, B & G, 3.0-5.1%. Since 1986, the sharp decrease of the resistant strains was noted. 5. Multiresistant strains to TC, CP and macrolides were found since 1980 to 1982. They were found in many of group A and a few of group B and G, but after 1986 decreased sharply. 6. Most of the multiresistant strains of group A belonged to serotype T-12 and group B to serotype Ia. Ia/c, III and III/R. 7. Among the strains of group A type T-13, there were many resistant strains to TC. The rate of resistant occupied over 60% from 1980 to 1986, but decreased slightly thereafter. PMID- 8207296 TI - [Long term observation on beta-hemolytic streptococci in institutions for handicapped preschool children. Streptococcal Diseases Study Group]. AB - Studies on beta-hemolytic streptococci have been carried out in 2 institutions for handicapped preschool children during the last nine-year period from 1985 to 1993. These studies were based on continuous throat cultures, 4 to 12 times a year, from 244 children including Down's syndrome and mentally retarded children in K-institution (K), and from 134 including cerebral palsy and other cerebrospinal disorders in H-institution (H). A significant difference (p < 0.05) was demonstrated in the isolation rates between K (11.1%) and H (6.4%). In K, isolation rates of beta-hemolytic streptococci ranged from 0 to 43.5%, showing a higher rate in winter (16.5%) than in summer (6.6%), and elevated-isolation rates of homologous types were demonstrate four times during the study period; i.e., type T12 in '87, type T28 in '88, type T1 in '90 and '92. In H, on the other hand, no higher rates (as to group A) were observed in winter or summer. In relation to disorders of children, the rates were 12.6% in Down's syndrome (mean age 2.7y), 10.0% in mentally retarded children (3.9y) and 6.4% in cerebral palsy or others with cerebrospinal disorders (3.3y). Down's syndrome, the youngest group, revealed the highest isolation rate of beta-hemolytic streptococci. In only two cases isolated hemologous types detected were over two times continuously. PMID- 8207297 TI - [Human fibrinogen binding activities in culture supernates of group A streptococci. Streptococcal Diseases Study Group]. AB - Fibrinogen binding activities in culture supernates of group A streptococci were detected by dot blot assay using horseradish peroxidase conjugated human fibrinogen. Various intensities in colored dots were seen in 63 of 70 strains isolated from pharyngitis patients in 1992. Strong binding activities in all of 16 strains were partially sensitive to trypsin digestion. The binding activities in the concentrated culture supernate of M-type 4 strain SS91 were analysed by SDS-PAGE and Western blotting. Intense colored bands and faint ones were seen in the position corresponding to 89K, 66K, 59K, 49K, 42KDa and 77K, 53K, 51K, 44KDa, respectively. Only one band at 42KDa remained after trypsin digestion. PMID- 8207298 TI - [Isolation of Group B streptococci from urine in healthy persons. Streptococcal Diseases Study Group]. AB - It is known that the neonatal group B streptococcal disease in most cases is acquired by contamination during passage through the birth canal at the time of delivery. Therefore, to investigate the influence of colonization of group B streptococci in the female genital tract by age, we carried out the isolation of group B streptococci from the urine of healthy children of school age group, and those age groups were as follow: kindergarten primary school students, junior high school students, high school students and women over twenty years of age. The isolation rates of group B streptococci from the urine of the healthy persons by each group were as follow: 12.5-18.2% in 93 females and 0-0.3% in 90 males in kindergarten aged 3-5 years, 6.4-25.3% in 285 females and 0.3-3.2% males in primary school aged 6-11 years, 11.8-19.1% in 183 females and 0-7.1% in 233 males in junior high school aged 12-14 years, 16.4-23.7% in 416 females and 2.6-7.1% in 114 males in high school aged 15-17 years, and 35.0-50.0% in adult females aged 20-60 years. Isolation rates according to sex were 2.2% in 756 males to 17.5% in 977 females of aged 3-17 years, and there was a clearly highly significant difference between males and females (p < 0.01). Group B streptococci isolated from urine of 1,818 persons were 220 strains (12.1%), and the 146 (66.4%) in all strains could be typed by the serological test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207299 TI - Cloning and nucleotide sequence of type 3 M protein gene (emm3) consisting of an N-terminal variable portion and C-terminal conserved C repeat regions: relation to other genes of Streptococcus pyogenes. Streptococcal Diseases Study Group. AB - The structural gene for type 3 M protein of Streptococcus pyogenes, which consists of an N-terminal variable portion and C-terminal conserved repeat regions, has been cloned by the polymerase chain reaction (PCR) with two primers (K-1 and K-2). They were selected from the best conserved region of the leader sequences and of the C-terminal portion near the Hexapeptide (LPSTGE) sequence found in different M proteins. From the nucleotide sequence of the product, 1645 base pairs were determined, including 32 amino acids of the leader sequences, the complete N-terminal variable region and the conserved C repeat region. Analysis of the deduced amino acids of the sequence revealed the existence of two major repeat regions, the B and C repeat regions. Comparison of the C-repeat regions among M3 and other M proteins showed them to be more than 90% identical. The two B repeat blocks in M3 protein are also similar to those in M12 protein. Predictive secondary structure analysis of M3 protein reveals a strong alpha helical potential. The algorithm also shows that the beta-sheet and turn potential for region 23-42 in M3 protein are similar to those for region 28-50 in M12 protein. The results indicate that M3 protein is closely related to M12 protein. PMID- 8207300 TI - [M-typing of Streptococcus pyogenes by latex agglutination using monoclonal antibody. Streptococcal Diseases Study Group]. AB - The Lancefield's serotyping system of Streptococcus pyogenes is based on the M protein. The typing sera used for this system are prepared in rabbits immunized with whole organisms of specific serotypes. To remove cross reactive antibodies, the sera should be extensively absorbed with organisms of selected heterologous serotypes. In this study, the possibility of using monoclonal antibody (MAb) as a type specific reagent was discussed. MAb which specifically reacted to M type 12 protein of S. pyogenes were produced by cell fusion. This specific MAb reacted to hot acid extracted M type 12 protein in ELISA but didn't react in agglutination and precipitation. Latex beads were sensitized with MAb and examined by the coagglutination method. The latex reagent could detect a very small amount of M type 12 protein, so it could be used for M typing of S. pyogenes which produced a small amount of M 12 protein. PMID- 8207301 TI - [Detection of carriers of group B streptococci in pregnant women with absorbed charcoal culture. Streptococcal Diseases Study Group]. AB - For prevention of group B streptococcal (GBS) infection in neonates, GBS carriers of pregnant women should be detected. Procedures for detection of carriers were needed to get higher positive rate and to be handled with easy. Urine samples were shown to detect higher rates than vaginal smear samples in pregnant women. GBS in the urine were adsorbed to charcoal granula for easier transporting. These adsorbed charcoal were tested as to whether they could be preserved with different temperatures and days. Urine with 10(1) CFU/ml of GBS added could be detected after 7 days at temperatures of 4, 25, 37, 42 degrees C. The cultures of this procedure with the cultures of urine sediment of pregnant women were compared. Detecting rates of this procedure and urine sediment were 177 (26.2%) and 136 (20.1%) of 676 pregnant women, respectively. These data suggested that adsorbed charcoal culture was useful with higher positive rates for detection of the GBS carriers in pregnant women. PMID- 8207302 TI - Smoking and erectile impotence. PMID- 8207303 TI - Pathologic aspects of carotid plaques: surgical and clinical significance. AB - From January 1988 to December 1989, we performed a total of 278 carotid thromboendarterectomies. The endarterectomized plaque was systematically confined for anatomopathological analysis by standard light microscopic techniques. The authors looked for clinicopathologic correlation of the histology of the endarterectomy specimen with the clinical data. Twenty eight plaques were not suitable for analysis and classification. The remaining 250 plaques were subdivided in 216 (36%) complicated plaques and 34 (14%) simple fibrous plaques. In the complicated plaques, the pathologist described one or more of the following pathologic characteristics: organized intraplaque hematoma (observed in 115 plaques), fresh thrombus (50), ulceration (92), and recent intraplaque hemorrhage (168). More than one anatomopathologic aspect were observed in most of the complicated plaques. Fifty three percent of these complicated plaques were symptomatic with corresponding neurologic deficit (amaurosis, TIA, RIND or stroke), versus 21% of the simple plaques (p < 0.001). For plaque characteristics the only significant clinicopathologic correlation was found in plaques with fresh thrombus which were symptomatic in 70% of cases, and ulcerated plaques (symptomatic in 66% of cases). This comparative study yielded no significant evidence of increased predisposition to neurologic deficit for the other morphological aspects (intraplaque hemorrhage, healed ulceration, organized hematoma). The histology of the endarterectomy specimen was compared with the preoperative echopattern of 154 plaques. Thirty four ultrasound images were of poor quality. The 120 adequate echographies revealed 22 dense hyperechogenic homogenous plaques, 28 soft hypoechogenic homogenous plaques, 53 inhomogenous plaques, and 13 mixed plaques. According to the surface, lesions were subdivided as smooth (N. = 63) or irregular (N. = 57). Echography recognized fibrous plaques (dense homogenous hyperechogenous lesions), with a specificity of 87% and a sensitivity of 56%. Recent intraplaque hemorrhage is echographically apparent as a hypoechogenic area in 88% of cases, what corresponds to a specificity of 79% and a sensitivity of 75%. Echography proved to be more accurate than angiography in determining the presence or absence of ulceration. The study evidenced that plaque morphology rather than luminal narrowing plays a primary role in cerebral ischemic disease. The ability to characterize the pathology of carotid atheroma by duplex scan makes the clinicopathologic correlation of carotid plaques of practical importance. PMID- 8207304 TI - Multifocal peripheral and coronary angioplasties. AB - Multifocal atherosclerotic lesions are frequent. It could thus be expected that multifocal angioplasties (performed in one particular patient on several [iliofemoral, renal, subclavian, mesenteric, coronary] sites) are frequent. To study multifocal angioplasty, we considered the 5344 angioplasties (PTA) (4151 coronary and 1193 peripheral PTA) which had been performed over 10 years in our institution. Eighty PTA (1.5%) were considered as multifocal angioplasty. They were performed in 30 patients who were followed up during 7 to 132 months (mean = 55). In case of primary PTA (72 PTA), the most frequent involved site was the iliofemoral site (47%) followed by renal (35%), coronary (8%), subclavian (7%) and mesenteric sites (3%). Eight PTA were performed after primary failure (3 cases) or after restenosis (5 cases). The 30 patients were divided into 2 groups according to the chronology of multifocal PTA. In group I, 20 patients had multifocal lesions on the first workup and multifocal angiopathy over a short operative period (< 3 months). The 10 patients of group II initially had a single procedure. They subsequently had multifocal angioplasty over a longer period (> 2 years) on different sites of the first PTA. Compared to group I, mean age was lower in group II (46 vs 52 year; ns), primary success rate higher (100 vs 90%; p < 0.05), complications less frequent (3 vs 20%, p < 0.05) and restenosis rate lower (7 vs 21%; p < 0.01). In conclusion, multifocal angioplasty is infrequent. A specific group of patients who had multifocal angioplasty spread over several months or years could be individualized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207305 TI - Surgical management of abdominal aortic aneurysms in Poland. A multi-centre study. AB - Abdominal aortic aneurysm resections were performed on 941 patients between 1987 and 1991 in nine selected university vascular units in Poland. The aim of the study was (1) to determine how grave the problem of abdominal aortic aneurysms is in the main vascular centres in our country, (2) to evaluate the methods of management, (3) to trace the most common postoperative complications, and (4) to estimate results. Hospital mortality rate for 730 elective and urgent resections was 8.2%. The emergency resection mortality rate for ruptured aneurysm was 60.2%. The most common postoperative general complications were: cardiac (178-18.9%), pulmonary (76-8.1%), renal failure (58-6.2%) and cerebrovascular accidents (23 2.4%). The postoperative local complications (113) occurred in 87 (9.2%) patients. The most common were: colon ischemia (22-3.5%), haemorrhage (30-3.2%), acute graft occlusion (22-2.3) and peripheral embolism (19-2%). Sixty-five patients required early reoperation undergoing a total of 74 additional operative procedures. The local complications occurring in analysed material significantly influenced the results. Mortality in reoperated patients was almost twice as high as among those not reoperated (p < 0.01). Analysis of the material revealed no differences in the obtained results of aneurysm surgery in the succeeding years of our study, when expecting improvement in the last years. The cause of this could be treatment of more high risk patients. The absolute number of patients with abdominal aortic aneurysms referred to the unit influenced results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207306 TI - Proposed training requirements for Medical Angiology fellows. European Working Group on Medical Angiology. PMID- 8207307 TI - Obesity, hypertension and atherosclerosis. AB - Hypertension and obesity are associated with an increased risk of clinical cardiovascular complications due to atherosclerosis. Moreover has been reported that hypertension may predispose to atheroma development. In the present review some common aspects to hypertension and atherosclerosis including smooth muscle cell proliferation, endothelial damage and intervention of growth factors have been analyzed. Additional data have to be provided to explain if the connections between hypertension and atherosclerosis could be considered two effects with one unknown cause. In addition some aspects related to obesity and atherosclerosis have been dissected. In particular we have reported our results indicating that young obese subjects without risk factors for cardiovascular disease have already several markers of cardiovascular damage i.e. atherogenetic lipid pattern, pro thrombotic and hypofibrinolitic pattern without sign of coagulation and/or platelet in vivo activation, increased plasma endothelin and catecholamine values, rised fasting and after OGTT insulin levels. In view of this more extensively data have to be necessary to support the opinion that obesity and atherosclerosis could be two associated conditions evolving during the time to develop cardiovascular disease or events. PMID- 8207308 TI - Is vascular disease in the female different from men? AB - Therapeutical management of cardiovascular disease has been based on the results from clinical trials of which the majority of the included patients are men. There is now more evidence that risk factors for female cardiovascular patients are different than for male patients. There is even a sex difference in the management of cardiovascular disease in general. Retrospective studies have shown a beneficial effect of postmenopausal hormone replacement therapy on the reduction of cardiovascular morbidity and mortality and stroke as well. However, there are conflicting data in the literature and prospective studies are necessary. More attention has to be paid to cardiovascular disease in the female and studies of precise circulatory differences between sexes are recommended. PMID- 8207309 TI - Cholesterol and fibrinogen as predictive factors of progressive carotid atherosclerosis. AB - In order to detect the presence of determining factors as predictors of progressive carotid atherosclerosis, the incidence of total serum cholesterol and fibrinogen elevation was evaluated in patients affected by coronary artery disease (CAD). 61 subjects with CAD (mean age 62 years) and significative lesions (> 50%) underwent periodic Echo-Doppler (Duplex scanning) of the supra aortic branches. Total serum cholesterol, HDL, LDL and fibrinogen were monitored, as well. A 24 month follow-up period was performed. Indicative of the progression of carotid atherosclerosis has been considered the presence of a stenosis degree over 20% than the initial one. In 14 of the 61 subjects who entered the study, there was evidence of progressive carotid atherosclerosis. The same patients showed higher levels of LDL cholesterol (130 +/- 36.3 vs 96.5 +/- 33.2) and Fibrinogen (398.3 +/- 59.4 vs 328 +/- 36.8) and lower levels of HDL cholesterol (27.2 +/- 4.2 vs 34.4 +/- 10.1). Our results confirm the importance of cholesterol and fibrinogen as determining risk factors, especially in patients with multiple vascular disease (coronary and carotid). PMID- 8207310 TI - Prevalence and prognostic value of peripheral arterial disease in stroke patients. AB - As atherosclerosis is a multi-systemic disease, each patient presenting clinical manifestation of atherosclerosis such as a stroke or RIND should be, from a vascular point of view, globally evaluated. The availability of Doppler ultrasound technique enables us to discover the presence of Peripheral Artery Disease (PAD) which is not always overt in the patient's history. Furthermore the presence of PAD is associated with a poorer prognosis in stroke patients. PMID- 8207311 TI - Effects of nicardipine on intimal-medial thickness and arterial distensibility in hypertensive patients. Preliminary results after 6 months. AB - BACKGROUND: The aim of this study was to evaluate the effects of nicardipine, at the dosage of 80 mg/day in two administrations, on blood pressure, intimal-media thickness of the common carotid artery and on arterial distensibility after 6 months of therapy. The study population consisted of 23 patients, 13 male and 10 female, mean age 61.7 +/- 10.1 years, with systolic blood pressure 170.4 +/- 14.5 mmHg and diastolic blood pressure 98.3 +/- 5.7 mmHg, affected by essential arterial hypertension of slight to moderate degree. Twenty-three subjects underwent high resolution B-mode echotomography of the common carotid artery, performed twice by the same operator within a one-week period. Treatment for 6 months with slow release Nicardipine at a dosage of 80 mg in two daily administrations was seen to be efficient in reducing systolic and diastolic blood pressure values. It also reduced the carotid-femoral pulse wave velocity. The results of our study show that 6 month's treatment with slow-release Nicardipine at 80 mg in two daily administrations, in effective reducing systolic and diastolic blood pressure values, and, to a slightly significant degree, in reducing the value of the intimal-medial thickness of the common carotid. Naturally the data which emerge from our study are preliminary and require a definitive analysis at the end the study, which is foreseen after a two year period from the enrolment of at least one hundred patients. PMID- 8207312 TI - Glutathione transferase activity in human vessels and in cultured arterial smooth muscle cells. AB - Glutathione transferases play an important role in the detoxification of many different endogeneous and exogenous compounds such as metabolites of polycyclic aromatic hydrocarbons (PAH) of cigarette tar. There is evidence that PAH may be atherogenic. The glutathione transferase activity towards trans-stilbene oxide (GST-tSBO) can be separated in blood in GST-positive and GST-negative phenotypes. We have previously suggested that the GST-negative phenotype may be associated with a higher morbidity in intermittent claudication among middle aged smokers. In the present study, GST-tSBO could easily be measured in human, rabbit and bovine arterial smooth muscle cells (SMC) in culture. The level of GST-tSBO was higher in rabbit than in bovine SMC. It was stable in bovine SMC during 5 cell passages and it could be induced twofold by long-time incubation with dimethylsulfoxide-soluble particulate matter from cigarette smoke or 3,4 benzo(a)pyrene. There was a positive correlation between the level of GST-tSBO in blood and in "healthy" arterial and venous tissue from individuals operated with coronary bypass. The enzyme levels in arterial tissue were lower than in venous tissue. GST-tSBO in atherosclerotic segments of human arteries was lower than in "healthy" segments from the same artery. These findings suggest that the arterial wall may have a low defense against toxic compounds that may decrease further as atherosclerosis proceeds. It is concluded that SMC are suitable for the study of the effects of PAH in relation to GST-tSBO and that the enzyme activity in blood will reflect the individual GST-tSBO phenotype also in vascular tissues. PMID- 8207313 TI - Plasma thrombomodulin: new approach of endothelium damage. AB - Endothelium damage is associated with thrombotic risk in a variety of diseases including atherosclerosis, gram negative sepsis, viral infections and neoplastic disease. Therefore, it appears necessary to find a mean for the clinical investigation for such a damage. Among the markers of these cells, thrombomodulin which is a membrane glycoprotein, seems to be of great interest for this purpose. Actually, thrombomodulin is also found in plasma, following an endothelial lesion. Plasma levels of thrombomodulin are increased in a certain number of pathologies associated with endothelium lesion: atheromatous arterial disease, disseminated intravascular coagulation syndrome and also in systemic lupus erythematosus where the levels of plasma thrombomodulin are related to the severity of the pathology. Moreover, previous in vitro studies confirm the fact that the release of thrombomodulin from the endothelial cell membrane occurs during the course of injury by activated leukocytes or hydrogen peroxide. So, one can suppose a prospective interest in the measurement of plasma thrombomodulin as a diagnostic tool for the approach of endothelium damage. PMID- 8207314 TI - Effect of medication with pravastatin sodium on hemorheological parameters in patients with hyperlipoproteinemia. AB - Pravastatin sodium, a newly developed potent synthesis inhibitor of HMG-CoA (beta hydroxy-beta-methylglutaryl-cocarboxylase-A) reductase (Sankyo Co., Ltd., Japan) was medicated, 10 approximately 15 mg/day (mean: 11.1 mg/day) for 10.2 weeks in mean, in 14 patients with primary hyperlipoproteinemia of more than 230 mg/dl of serum cholesterol levels (mean age: 56.9 y.o.). The values of serum cholesterol decreased (from 242 +/- 12 to 207 +/- 22; mg/dl), and of high density lipoprotein (HDL) increased (from 42.3 +/- 8.8 to 45.3 +/- 9.2; mg/dl) significantly (p < 0.05, respectively) 10.2 weeks in mean after medication with pravastatin sodium. The whole blood viscosity, at every shear rate examined, corrected blood viscosity, for the standard hematocrit level of 45%, and plasma fibrinogen decreased significantly (p < 0.05, respectively) at the same time, without showing significant differences any more 10.2 weeks in mean after medication with those in 14 elderly normal subjects (mean age: 56.7 y.o.), which suggested that the hemorheological parameters in patients with primary hyperlipoproteinemia had improved significantly by medication with pravastatin sodium. PMID- 8207315 TI - Diabetes, hypertension and atherosclerosis: pathophysiological role of intracellular ions. AB - The clinical coincidence of hypertension, obesity and non insulin diabetes mellitus (NIDDM) has long been recognized. Increasing interest has also been recently focused on the possible role of insulin and insulin resistance in mediating this association. There is also evidence that hyperglycemia per se may have a role in the pathogenesis of hypertension and atherosclerosis in NIDDM patients. Glucose is a determinant to cellular ion homeostasis, promoting an increase of intracellular calcium and suppressing intracellular free magnesium and pH. Moreover, hyperglycemia promotes glycosilation of proteins and the consequent accumulation of advanced glycosilation end products in tissues. It has recently been suggested that iter is a cellular ionic basis for the clinical and epidemiological linkage of hypertension, left ventricular hypertrophy (LVH), obesity and non insulin dependent diabetes mellitus (NIDDM). These clinical conditions may be different expressions of a common underlying defect in ion handling, displayed by elevated cytosolic free calcium and suppressed free magnesium levels. Therapeutically, reversal of this excess free calcium accumulation and/or free magnesium deficit with ion specific agents, such as calcium channel blocker drugs, may thus ameliorate not only the elevated blood pressure of hypertension but also the concurrent cardiac, vascular and metabolic aspects of the hypertensive states. PMID- 8207316 TI - Double-blind, controlled, multicenter study of indobufen versus placebo in patients with intermittent claudication. AB - The objective of the study was to evaluate the efficacy and safety of indobufen compared with placebo in the treatment of moderately severe intermittent claudication. The study consisted of a four-week single-blind, placebo-controlled run-in phase, followed by a six-month double-blind randomized treatment period. A total of 302 patients were allocated to treatment with either placebo (154 patients) or indobufen (148) 200 mg twice daily. The results of the overall intention-to-treat analysis of the study population showed statistically significant superiority of indobufen over placebo after six months for both the initial (ICD) and absolute claudication distances (ACD). The ICD before treatment with indobufen or placebo averaged 137.9 +/- 68.2 and 136.6 +/- 63.2 m (mean +/- SD), respectively. After six months' treatment with active drug or placebo, this parameter reached 227.9 +/- 174.4 and 153.1 +/- 86.8 m (mean +/- SD), respectively (p < 0.01). Similar results were obtained on ACD. The reduction of lower limb symptoms also suggested a greater clinical benefit in the indobufen treated patients. There was no significant change in either group in the ankle/arm pressure ratio at the end of treatment. Adverse events of any type were reported by 18 patients (12.2%) in the indobufen group and by 11 patients (7.2%) in the placebo group. The mechanism whereby the drug is effective in this clinical condition could be related to both its antiplatelet and hemorheologic effects. PMID- 8207317 TI - Prevention of deep venous thrombosis by a new low molecular weight heparin (Fluxum) in cardiac surgery. AB - The prophylactic deep venous antithrombotic efficacy of a low molecular weight heparin (LMWH) was compared with traditional unfractionated calcium heparin in 39 patients submitted to cardiac surgery. The patients were allocated at random to receive either LMWH-Fluxum 3200 IUaXa daily (Group A: 20 patients) or calcium heparin 5000 IU three times daily (Group B: 19 patients). Both treatments were started on the first day after surgery and continued over the fourth postoperative days. One or more risk factors for deep venous thrombosis in addition to the cardiac pathology were present in all the patients of group A and in 13 (72.2%) of group B. Mean times of surgery, blood loss during the perioperative period and number of blood units transfused in both groups were not statistically significant. The deep venous system was investigated by continuous wave Doppler and real time colour Echotomography. No evidence of thrombosis was detected in the two groups. Side effects and subcutaneous hematomas were present in only four patients of group B. Both drugs showed good tolerance, provoking no variations of the main laboratory parameters. We conclude that Fluxum (LMWH) for the efficacy and convenience given by a single daily dose, could represent an alternative choice in the prevention of deep venous thrombosis in cardiac surgery. PMID- 8207318 TI - Toxicity of insulin administered chronically to human eye in vivo. AB - Insulin administered in eyedrop from with a surfactant agent has been shown to be clinically effective in treating diabetes in animal models. Concentrations of insulin as high as 100 U/ml in saline were shown to produce no detectable clinical toxicity to human eyes in single-dose administration. We sought to investigate the local toxicity of insulin in human eyes during long-term, multidose administration. A prospective, randomized, placebo controlled, double masked study was conducted involving eight healthy volunteers. Subjects were given 50 microliters sterile saline containing 100 U/ml crystalline porcine insulin randomized to one eye and 50 microliters placebo (sterile saline) to the fellow eye administered twice daily for 8 weeks. Subjective ocular irritation and visual acuity and objective assessment of the eyelids, conjunctiva, cornea, anterior chamber, crystalline lens, pupil size, and intraocular pressure were evaluated. Blood D-glucose levels were monitored to assess glycemic levels. There was no statistically significant difference (p > 0.05) observed between insulin treated and placebo-treated eyes. Eyedrops containing insulin were subjectively as comfortable and objectively as clinically innocuous as sterile saline alone. The results of this study demonstrate that insulin (100 U/ml) in saline is nontoxic to the human eye after long-term, multi-dose exposure. Topical administration of insulin combined with an absorption-promoting agent may be a practical and feasible alternative to multiple daily subcutaneous injections or implanted pump devices currently used in the long-term treatment of diabetes mellitus if a nonirritating absorption-promoting agent can be identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207319 TI - Functional consequences of prejunctional receptor activation or blockade in the iris. AB - The iris is innervated by nerves of the sympathetic, parasympathetic, and sensory nervous systems. The terminal nerve fibres are endowed with prejunctional receptors which modulate neurotransmitter release. Activation or blockade of prejunctional receptors by drugs may have an influence on iris smooth muscle tone. Several findings are in favour of the hypothesis that prejunctional receptors may be involved in regulation of iris smooth muscle tone and/or pathophysiological events. (i). Release of acetylcholine from parasympathetic nerves of guinea-pig iris sphincter evoked by electrical stimulation is subject to autoinhibition via prejunctional M2 muscarinic receptors, and the release can be enhanced by M2 selective antagonists such as methoctramine or gallamine. Concomitantly with the increased neurotransmitter release, the sphincter contraction is enhanced in the presence of M2 antagonists, since the postjunctional muscarinic receptors (presumably M3, or at least not M2) are not simultaneously blocked. Unlike the non-selective blocker atropine, M2 antagonists are not expected to cause mydriasis but rather miosis. (ii). Sensory nerves are involved in pathophysiological events following ocular irritation. Release of substance P and/or neurokinin A from sensory nerves of rabbit iris is followed by a non-adrenergic-non-cholinergic iris sphincter contraction (mediated by NK1 and NK3 receptors) which can be used to estimate sensory neurotransmitter release. Exocytotic release of the sensory neurotransmitters is inhibited by activation of alpha 2B-adrenoceptors and probably also via putative prejunctional imidazoline receptors. Alpha-adrenoceptors are stimulated by oxymetazoline and other imidazoline derivatives (which are agonists at imidazoline receptors) leading to a reduction of sensory neurotransmitter release, as evident from a decrease in evoked sphincter contraction. Imidazolines in eye drops may not only cause relief in ocular inflammation due to postjunctional vasoconstriction but also possibly due to a prejunctional effect, a reduction of sensory neurotransmitter release. Reinforcement of inflammation due to release of sensory neurotransmitters may thus be prevented. PMID- 8207320 TI - Characterization of muscarinic receptor involvement in human ciliary muscle cell function. AB - Muscarinic agonist-induced contraction of the ciliary muscle is generally believed to increase aqueous outflow facility and effect accommodation. We used cultured human ciliary muscle cells as a model to study the muscarinic receptor subtype(s) involved in the contractile response of the muscle. Thus, a single cell contraction assay for these muscle cells was developed. And since agonist induced contraction of smooth muscles is expected to involve the activation of phospholipase C (PLC), we also monitored the PLC activity in these cells. Carbachol caused contraction of the muscle cells in a dose-dependent and time dependent manner with an estimated EC50 of 1-3 microM. The contractile effect of 100 microM carbachol was antagonized by pretreatment of atropine (1 microM) and 4DAMP (10 nM, antagonist selective for the M1 and M3 receptors) but not by pirenzepine (10 microM, antagonist selective for the M1 receptor), suggesting the involvement of the M3 but not the M1 muscarinic receptor. M3 receptor is also essential for the carbachol-induced PLC activation in the ciliary muscle cells, as indicated by the activity profiles of receptor subtype selective antagonists. For example, the stimulative effect of carbachol (EC50 = 20 microM) was antagonized by pirenzepine (pKi = 6.8), HHSiD (pKi = 7.6), 4DAMP (pKi = 9.5) and methoctramine (pKi < 6). Thus, these results indicate that an M3-like receptor subtype is essential in mediating the muscarinic agonists-induced functional changes, such as PLC activation or muscle contraction, in the ciliary muscle. PMID- 8207321 TI - M3 muscarinic receptors mediate an increase in both inositol trisphosphate production and cyclic AMP formation in dog iris sphincter smooth muscle. AB - Pharmacological studies on pirenzepine (PZ), 4-diphenylacetoxy-N-methyl piperidine (4-DAMP) and AFDX-116 antagonism of carbachol (CCh)-induced contraction, inositol trisphosphate (IP3) production and cAMP formation revealed the involvement of M3 receptors in these responses. The PA2 values for PZ and 4 DAMP antagonism to CCh-induced contraction were 7.1 and 9.0, respectively, and AFDX-116 had no effect on these responses. Further, 4-DAMP was a much more potent inhibitor than PZ of CCh-stimulation of IP3 production and cAMP formation. Both L type calcium channel blockers, which inhibit Ca2+ influx, and BAPTA, an intracellular calcium chelator, inhibited these biochemical and pharmacological responses due to CCh. It is concluded that both intracellular and extracellular Ca2+ mobilization are involved in muscarinic stimulation of cAMP production, and that M3 receptors are coupled to the activation of both phospholipase C and adenylate cyclase in this tissue. The data presented here are consistent with previous work that stimulation of muscarinic receptors in dog iris sphincter with CCh (> 5 microM) increases intracellular cAMP levels. PMID- 8207322 TI - Solubilization and characterization of PGE2 receptor in porcine ciliary epithelium. AB - PGE2 binding sites or receptors of porcine ciliary nonpigmented epithelial (NPE) and pigmented epithelial (PE) membranes were solubilized with detergents (CHAPS and Triton X100). From the Scatchard plots of PGE2 binding to CHAPS-solubilized proteins, the Kd and Bmax values were calculated to be 35 nM and 470 fmol/mg protein for NPE protein and 65 nM and 430 fmol/mg protein for PE protein, respectively. On the basis of the Kd and Bmax values, the solubilized receptor proteins correspond to PGE2 binding sites of the membranes which have previously been shown to be coupled to adenylate cyclase inhibition. For both NPE and PE proteins, the order of binding potency was PGE2 > PGF2 alpha > PGD2. By gel filtration chromatography of NPE and PE proteins, the molecular mass of the major PGE2 binding peak was estimated to be about 150 KDa when solubilized in CHAPS and 46 KDa for Triton X100 extracts. The Bmax values of membrane-associated binding proteins were increased by GTP, indicating a close association of the PGE2 binding sites with a GTP-binding protein. However, GTP did not affect the Bmax values of detergent-solubilized receptor proteins. PMID- 8207323 TI - Studies on prostanoid receptors in ocular tissues. AB - Cyclooxygenase products of arachidonic acid, for example prostaglandins (PGs), prostacyclin, and thromboxane A2, mediate a wide range of physiological actions. Vasodilation, increased vascular permeability, platelet aggregation and its inhibition, and immunomodulation are some of the important biological actions of cyclooxygenase products (1). Depending on type and dose, PGs cause vasodilation, increase or decrease intraocular pressure, and disrupt the blood-aqueous barrier (2, 3). These actions also vary qualitatively and quantitatively with the animal species. Prostaglandins, like any biological molecule, must act by binding with their specific receptors. Coleman and coworkers (4, 5), from a series of studies with PG agonists and antagonists in vascular and non-vascular smooth muscle preparations, classified PG receptors. This classification led to a greater appreciation of the relationship between PG actions and specific PG receptors in various tissues. Ocular actions of PGs linked with specific PG receptors are far from being clear. In this communication we will review our work on PG binding sites in ocular tissues and PG receptors coupled to adenylyl cyclase or phosphoinositidase C signal transduction pathways in ocular tissues of various animal species. PMID- 8207324 TI - Collagen-based drug delivery and artificial tears. AB - For patients with conditions requiring chronic rather than acute therapy, the advantages of collagen shields in providing high and sustained levels of drugs and/or lubricants to the cornea are outweighed by the difficulty of insertion of the shield and the problem of blurred vision. We have developed a delivery system in which collagen pieces suspended in a viscous vehicle can be instilled into the lower forniceal space, thereby simplifying application and reducing blurring of vision. The collagen pieces (Collasomes) can be formulated with various constituents such as antibiotics or cyclosporine, or with chemical alterations such as the inclusion of a lipid (Lacrisomes) for the treatment of dry eyes. In the normal eyes of volunteers, Collasomes hydrated in a solution of sodium fluorescein and suspended in a methylcellulose vehicle as a model for delivery of water-soluble drugs produced fluorescein concentrations 17 to 42 times higher in the cornea and 6 to 8 times higher in the aqueous humor, compared with fluorescein-containing vehicle alone. In a preliminary controlled study, 76% of patients with moderately severe keratoconjunctivitis sicca (KCS) preferred Lacrisomes to the vehicle control because of a more soothing effect and longer duration of comfort. All preparations were well tolerated by all study subjects. Current studies involve improving drug delivery by chemically modifying the collagen molecule to slow diffusion of the drug from the Collasome matrix, as well as varying the amount of cetyl alcohol and combining it with modified collagen in Lacrisomes to maximize comfort in patients with dry eyes. PMID- 8207325 TI - Studies on the ocular hypotensive effects of prostaglandin F2 alpha ester prodrugs and receptor selective prostaglandin analogs. AB - The use of natural prostaglandins (PG), such as PGD2, PGE2, PGF2 alpha, and PGI2, for treating glaucoma is limited by their ocular side effects. One approach to achieve the required separation of ocular hypotensive activity from side effects is to employ ester prodrugs. From a novel series of 11- and 15-mono and 11,15 diacyl esters of PGF2 alpha we identified prodrugs where PGF2 alpha formation rates in the iris-ciliary body exceeded those in the conjunctiva, sclera, and corneal endothelium. Compared to PGF2 alpha-1-isopropyl ester the ocular tissue hydrolysis rates of the 11-monopivaloyl, the 11,15-dipivaloyl ester and the 1,11 lactone were up to 1000 fold less. Despite this large disparity in hydrolysis rates, the pivaloyl esters and the 1,11-lactone were potent ocular hypotensives in our animal models. In studying prostaglandin analogs, we found that a diverse variety of prostanoid receptor selective agonists lowered intraocular pressure in dogs and/or monkeys. These included DP-, EP1-, EP2-, EP3-, and FP-receptor selective compounds. These findings were surprising and prompted us to re-examine the receptor selectivity of these agonists by radioligand binding studies. Using radiolabelled PGE2, 17-phenyl PGF2 alpha, and sulprostone we were able to confirm the selectivity of the agonists currently used for receptor characterization directly by radioligand binding competition studies. It appears that multiple prostanoid receptor subtypes may be involved in regulating intraocular pressure. PMID- 8207326 TI - Nature of cholinesterase in the rat retina. AB - The occurrence of cholinesterases has been demonstrated in retinas of several mammalian species. Histochemical staining techniques indicate that the acetylcholinesterases (AChE) are present in amacrine cells and their neighboring bipolar cells. However, the nature of retinal cholinesterases and their interactions with specific cholinesterase inhibitors are not known. Therefore, we have studied the inhibition of the rat retinal cholinesterase activity by BW284C51, a selective inhibitor of AChE, and iso-OMPA, a selective inhibitor of butyrylcholinesterase (BChE). Retinas from Zivic-Miller rats were solubilized by sonication in phosphate buffer (0.134 M, pH 7.2) at 4 degrees C for 20 min. The cholinesterase activity in the sonicate was determined by a radiometric method using 14C-acetylcholine (ACh) as substrate (10(-2) M). Excess 14C-ACh was adsorbed by Amberlite CG-120 cation exchange resin. 14C-acetate formed and retained in the aqueous medium was determined by liquid scintillation counting. This study gave the following results: (a) Rat retinal sonicate gave total cholinesterase activity of 3.76 mumol of ACh hydrolyzed/mg protein/15 min; (b) This activity was inhibited by BW284C51 (IC50, 0.115 microM). Iso-OMPA (IC50, 500 microM) did not cause significant inhibition at 0.115 microM. These observations suggest that the rat retinal cholinesterase is predominantly AChE. PMID- 8207327 TI - Retinal cholinergic system: characterization of rat retinal acetyltransferases using specific inhibitors of choline- and carnitine-acetyltransferases. AB - Choline acetyltransferase catalyzes the synthesis of acetylcholine from choline and acetylcoenzyme A (ACoA) in both nervous and non-nervous tissues. Carnitine acetyltransferase occurs in several tissues and transfers acetyl groups from ACoA to carnitine forming acetylcarnitine and exhibits weak choline acetyltransferase activity. Several haloacetylcholines and haloacetylcarnitines were synthesized to develop selective inhibitors of choline acetyltransferase and carnitine acetyltransferase. Acetylcholine is a transmitter for some presynaptic neurons and/or amacrine cells in retina. Selective inhibitors of choline acetyltransferase and carnitine acetyltransferase were used in the evaluation of choline acetyltransferase and carnitine acetyltransferase activities in the rat retina. Choline acetyltransferase and carnitine acetyltransferase activities were assayed by transferring of [14C]acetyl group from [14C]ACoA to choline or carnitine and estimating [14C]-acetylcholine or [14C]acetylcarnitine. This study gave the following results: (a) Bromoacetylcholine (BrACh) was a selective inhibitor of purified choline acetyltransferase (I50, 2.2 microM); (b) (R) bromoacetylcarnitine [(R)-BrACa] was more potent for inhibiting purified carnitine acetyltransferase (I50, 4 microM) than purified choline acetyltransferase (I50, 46 microM); (c) Rat retinal sonicate gave choline acetyltransferase activity of 98 +/- 6 nmol of ACh formed/mg/10 min. When the carnitine acetyltransferase was completely inhibited by (R)-BrACa, the activity for choline acetyltransferase decreased to 47 +/- 1 nmol, and this decrease was possibly due to the formation of some [14C]acetylcholine by carnitine acetyltransferase. The net retinal choline acetyltransferase activity was 51 nmol acetylcholine/mg protein/10 min; (d) Rat retinal sonicate contained carnitine acetyltransferase activity of 102 +/- 7 nmol acetylcarnitine formed/mg protein/10 min. This was not altered by inhibition of choline acetyltransferase with BrACh. This means that choline acetyltransferase did not use carnitine as a substrate. Choline acetyltransferase and carnitine acetyltransferase activities did not change after dialysis of retinal sonicates at 4 degrees C for 24 hrs. These observations suggest that BrACh and (R)-BrACa are useful for assessing the correct values for choline acetyltransferase and carnitine acetyltransferase activities in retinal tissues. PMID- 8207328 TI - Relevance of drug-melanin interactions to ocular pharmacology and toxicology. AB - In melanocytes, the biosynthesis of L-dopa derived indole polymer, melanin, is accelerated by tyrosinase and related enzymes. The brown to black pigment is characterized by a stable free-radical property. In humans, a pigment dependent slow onset of ocular actions of ephedrine, atropine, cocaine, pilocarpine and related medications was observed. Extensive accumulation of drugs by melanin appears to be the most important factor governing the long term therapeutic/toxicological activities. Drugs crossing placental circulation are localized in the mouse fetal eye. Thus, drugs exhibit a high binding capacity for melanin containing tissues. Studies on synthetic melanin and melanin granules also indicated a high binding capacity of many therapeutic classes of drugs, including psychotropics. In addition to the liposoluble property of the molecule, there is a definite relationship between chemical structure and the affinity of drugs for melanin. For example, the affinity of chlorpromazine for melanin is higher than that of chlorprothixene. NMR studies, with soluble melanins indicate that there is a steric preference among ephedrine enantiomers. A high binding capacity indicates that more than two molecules of (-)-ephedrine may complex with one indole unit of melanin. Ocular drug development calls for the study of qualitative and quantitative aspects of drug-melanin interaction. PMID- 8207329 TI - S-adenosyl-L-methionine-mediated enzymatic methylations in the rat retinal membranes. AB - Enzymatic step-wise methylation of membrane phosphatidylethanolamine (PE) to phosphatidyl-N-methylethanolamine (PME) and then phosphatidyl-choline (PC) has been known to alter membrane properties and responsiveness of cells for activation of receptors by chemical transmitters. Conversion of PE to PME and PME to PC in the presence of S-adenosyl-L-methionine (SAM) are catalyzed by two phospholipid N-methyltransferases, PMT I and PMT II, of which PMT I is the rate limiting enzyme. Retina is a good neuronal model for chemical transmission. However, retina was not studied for PMT activity. Therefore, we studied the rat retina for PMT I activity. Methylation of PE in the rat retinal sonicates was assayed using 3H-SAM (2 microM) at 37 degrees C in Tris-glycylglycine buffer (50 mM, pH 8.0) and methylated phospholipids were extracted with chloroform/methanol/HCl (2/1/0.02, v/v) and separated by thin layer chromatography on Silica Gel G plates. Chromatograms were developed in a solvent system of propionic acid/n-propyl alcohol/chloroform/water (2/2/1/1, v/v). This study gave the following results: (a) the total methylated phospholipids were (M +/- SE, N = 5) 19.90 +/- 4.03 fmol/mg protein/min; (b) the major methylated phospholipid was PME (4.21 +/- 0.68 fmol/mg protein/min; (c) the fatty acid methylesters formed by fatty acid carboxymethylase (FACM) which accumulated in the solvent front amounted to 18.82 +/- 2.84 fmol/mg protein/min. Both PMT I and FACM were inhibited by S-adenosyl-L-homocysteine (I50, 1.2-5 microM). These observations indicate that rat retina contains both PMTs and FACM. PMID- 8207331 TI - Characterization of the inflammatory response induced by corneal infection with Pseudomonas aeruginosa. AB - In order to characterize the inflammatory response to corneal infection by Pseudomonas aeruginosa, ocular cytokine and arachidonic acid metabolite levels were determined in the C57BL/6J strain of mice. The effects of topical anti inflammatory drugs on the ability of the mice to clear viable P. aeruginosa from the eyes during the 12 day infection period was also examined. Ocular IL-1 alpha, IL-6, and TNF-alpha were detected over an 11 day time period. Little or no bacteria, as determined by quantitative plate counts, was detected after this time period. The kinetics of the cytokine production varied from one another, with an immediate release of peak levels of IL-1 alpha within 24 hours after infection which did not begin to approach baseline until 9 to 11 days after infection. Five to ten-fold lower concentrations of IL-6 and TNF-alpha were detected. IL-6 levels were induced at 24 hours after infection but there was essentially no distinct peak time-point. Peak levels of TNF-alpha were detected at 6 days post-infection. The kinetics of arachidonic acid metabolite release from infected eyes were also examined. Peak levels of PGE2 and TxB2 were observed at 6 days post-infection whereas peak LTB4 levels were determined at 3 days post infection. Topical treatment of infected eyes with the two anti-inflammatory drugs, prednisolone or quercetin, resulted in higher ocular bacterial levels throughout the infection. PMID- 8207332 TI - Loteprednol etabonate: comparison with other steroids in two models of intraocular inflammation. AB - Loteprednol etabonate (LE) is a novel steroid with a low tendency to raise IOP. It is metabolized in the eye to an inactive metabolite. The current study was undertaken to assess the intra-ocular anti-inflammatory activity of LE in two models of experimental uveitis in rabbits. In the endotoxin induced rabbit model, LE was effective at reducing measures of inflammation, but less so that either fluorometholone (FML) or dexamethasone. In the Freunds adjuvant chronic uveitis model, FML was also very effective with LE and dexamethasone showing similar activity. The data demonstrate that LE is effective at reducing intra-ocular inflammation. PMID- 8207330 TI - Effect of low molecular weight heparan sulphate on angiogenesis in the rat cornea after chemical cauterization. AB - Vascularization of the cornea occurs in many pathological conditions and can result in loss of visual acuity. It is also thought that vascularization predisposes the cornea to reject grafts by facilitating the detection of foreign antigens in donor material. A rat corneal assay for angiogenesis was adopted in the present study to evaluate the possible angiostatic activity of a low molecular weight heparan sulphate (LMW-HS). Corneal lesions were induced by chemical cauterization at 2 mm from the corneoscleral limbus. Rats were randomized to receive two drops/eye four times daily, for 6 days, of a solution of LMW-HS in vehicle (2.5% carboxymethylcellulose), heparin, heparin plus hydrocortisone, or vehicle alone. After a 6 day-treatment period, the eyes were perfused with india ink and the degree of neovascularization was evaluated. In rats treated with vehicle alone a dense vascular network extending from the corneoscleral limbus to the cauterized site was observed; on the contrary, a markedly reduced vascular network was evidenced in animals treated with LMW-HS. The distribution of basic fibroblast growth factor (bFGF) in the cauterized cornea was also evaluated by using an immunohistochemical method. A marked bFGF immunoreactivity was demonstrated in corneal epithelium and stroma of control rats 12-48 hours after the cautery. These results lead to the assumption that LMW HS could be used in ophthalmology to inhibit corneal neovascularization. PMID- 8207333 TI - Microparticulates for ophthalmic drug delivery. AB - Microparticulates are drug-containing small polymeric particles (erodible, non erodible or ion-exchange resins) that are suspended in a liquid carrier medium. Upon administration of particle suspension in the eye, the particles reside at the delivery site (cul-de-sac, sub conjunctiva or vitreous cavity) and the drug is released from the particles through diffusion, chemical reaction, polymer degradation, or ion-exchange mechanism. Several distinct approaches have been used to formulate drugs in microparticulate dosage form for intraocular and topical application. These include erodible microparticulates, swelling mucoadhesive particulates, pH responsive microparticulates, nanoparticles/latex systems, ion-exchange resins, etc. Injection of bioerodible microparticulates in the vitreous for treating infections of posterior segment and the release of acceptable levels of drug up to two weeks has been demonstrated. Both corneal and non-corneal routes of drug entry in the eye from topical instillations are postulated. The in vitro and in vivo studies have shown that this dosage form holds great promise for sustained drug release in the eye. However, several formulation challenges, including production of stable suspensions, uniform dose per unit volume, efficient drug entrapment, reproducible and large scale manufacturing, uniform particle size, etc., have to be addressed. Fruitful resolution of technological challenges will result in a superior dosage form for both topical and intraocular ophthalmic application. Recent developments and future challenges of microparticulate ophthalmic drug delivery system are discussed in this review. PMID- 8207334 TI - The induction of anterior chamber inflammation by factors released from hydrogen peroxide-injured corneas: effect of dexamethasone and indomethacin. AB - Studies from our laboratory have demonstrated the release of high levels of neutrophil chemotactic factors (NCF) from isolated rabbit corneas injured by hydrogen peroxide (H2O2). The purpose of the present study was to determine the biological activity of these factors and to test the hypothesis that the intracameral injection of these factors can induce inflammation of the anterior segment. Under sterile conditions, the epithelial surfaces of isolated rabbit corneas were incubated with a 300 ul mixture of glucose (G) (1mg/ml) and glucose oxidase (GO) (20 U/ml) at 37 degrees C for 6 hours. This supernatant solution was collected and a 100 ul sample containing NCF, but not H2O2, was injected into the anterior chamber of anesthetized rabbit eyes (n = 8). Anterior chamber inflammation, characterized by moderate corneal edema associated with a fibrinous anterior chamber reaction, was evident 2 and 4 hours after injection. Aqueous humor analysis revealed the presence of fibrin and a large number of neutrophils (32 +/- 5 x 10(4) cells/ml). Control eyes, on the other hand, showed normal morphology and low levels of neutrophils after the injection of 100 ul minimum essential medium (MEM) (n = 8) (1.2 +/- 0.14 x 10(4) cells/ml), G/GO mixture (n = 8) (5 +/- 0.86 x 10(4) cells/ml), or supernatant solutions collected from MEM treated corneas (n = 8) (15 +/- 2 x 10(4) cells/ml). To determine whether the inflammatory reaction observed was due to a direct effect of the chemoattractants or mediated through stimulation of arachidonic acid (AA) metabolites, we pretreated rabbit eyes with a sterile solution of 0.1% dexamethasone (n = 8 eyes) or with a sterile solution of 3.4% indomethacin (n = 8 eyes) three times a day, for one day, prior to the injection of NCF supernatant solution. Examination 2 hours and 4 hours after injection revealed inflammation characterized by mild-to moderate corneal edema associated with a fibrinous anterior chamber reaction was observed with or without prior treatment with AA metabolite inhibitors. No difference in the degree of inflammation was detected clinically. Results of these studies suggest that NCF released from H2O2-injured corneas can directly induce inflammation of the anterior segment, and that metabolites of AA are not mediating the observed in vivo response. PMID- 8207336 TI - Platelet-activating factor antagonists and ocular inflammation. PMID- 8207335 TI - Effect of metabolic inhibitors on arachidonic acid metabolism in the corneal epithelium: evidence for cytochrome P450-mediated reactions. AB - The corneal epithelium of several species, has the capacity to metabolize arachidonic acid (arachidonic acid) via an NADPH-dependent cytochrome P450 mechanism. The major metabolites are 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and 12-hydroxy-5,8,14-eicosatrienoic acid (12-HETrE), both of which exist in stereoisomeric configurations. However, the R enantiomers are predominantly produced by this enzyme system and exhibit potent biological activities. 12(R)-HETE inhibits Na-K-ATPase, increases corneal thickness and reduces intraocular pressure. 12(R)-HETrE causes vasodilation, neutrophil chemoattraction and angiogenesis. The formation of these metabolites is unaffected by cyclooxygenase and lipoxygenase inhibitors (indomethacin, diclofenac and BW755C) but inhibited by cytochrome P450 enzyme inhibitors such as carbon monoxide, SKF-525A and clotrimazole. The capacity of the normal corneal epithelium to metabolize arachidonic acid via cytochrome P450 is very low although under certain conditions this enzymatic pathway may become greatly induced. Corneal epithelial hypoxia in response to contact lens wear results in the time-dependent formation of NADPH-cytochrome P450-dependent arachidonate metabolites, 12(R)-HETE and 12(R)-HETrE. Under this condition, metabolite production correlates strongly with the in situ inflammatory response and inhibition of their formation significantly attenuates inflammation. It is evident that the cytochrome P450 arachidonate metabolites should be added to the realm of cyclooxygenase and lipoxygenase-derived eicosanoids as possible inflammatory mediators. Therefore, studies to evaluate eicosanoid involvement in inflammation should examine inhibitors of this pathway in addition to the classically studied non-steroidal antiinflammatory drugs (NSAIDs). PMID- 8207337 TI - Steroidal and nonsteroidal drugs in endotoxin-induced uveitis. AB - Various classes of anti-inflammatory compounds like steroids (dexamethasone), cyclooxygenase inhibitors (indomethacin and flurbiprofen), 5-lipoxygenase inhibitors (BWA 218C and BWA 4C), immunosuppressive drugs (cyclosporin and rapamycin) and cod liver oil were tested for their antiinflammatory activities in endotoxin-induced uveitis model in rabbits. Intraocular inflammation was assessed in terms of two inflammatory responses i.e. breakdown of blood-aqueous barrier (BAB) and leukocyte infiltration into aqueous humor and iris ciliary body (ICB). Prostaglandin (PG) E2 and leukotriene (LT) B4 release into aqueous humor was also measured. Indomethacin significantly inhibited PGE2 release without affecting leukocyte or BAB response. Flurbiprofen prevented leukocyte, PGE2 and LTB4 release into aqueous humor but not ICB chemotaxis. BWA 218C and BWA 4C also significantly inhibited leukocyte and LTB4 release but not BAB responses. Dexamethasone (2mg/kg, i.m.) and cyclosporin A (25 mg/kg i.m.) significantly inhibited leukocyte infiltration into aqueous humor and ICB, and PGE2 release but they failed to inhibit breakdown of BAB and LTB4 release. On the other hand, rapamycin (10mg/kg i.m.) and cod liver oil (1 ml daily i.m. up to 15 days) significantly prevented leukocyte and BAB response. Cod liver oil also significantly inhibited PGE2 and LTB4 release but rapamycin affected only PGE2 release into aqueous humor. It is concluded that arachidonic acid metabolites may not play a vital role in this uveitis model and additional proinflammatory mediators like cytokines may be involved. PMID- 8207338 TI - Prevention and treatment of ocular inflammation with a new class of non-steroidal anti-inflammatory agents. AB - New non-steroidal anti-inflammatory agents (NSAIAs) were tested on lens protein-, endotoxin- and interleukin-1-induced ocular inflammation. It was found that most NSAIAs, including REV 5901, mefenamic acid, indomethacin, CK-17 and CK-102, inhibited lens protein-induced inflammation. Endotoxin induced inflammation indirectly through the release of IL-1 which was inhibited by fewer agents, including CK-17, CK-102 and prednisolone. However, the direct effect of IL-1 can only be suppressed by CK-17 and prednisolone. Therefore, CK-17 could become an important NSAIA which acts similarly to corticosteroids yet produces no steroidal side effects. CK-17 was different from most NSAIAs as it affected little, if any, arachidonate metabolism. Most importantly, CK-17 was found to be 2-fold more potent than prednisolone in inhibiting IL-1-induced uveitis, while no side effects were noted at doses tested to date. PMID- 8207339 TI - Delivery of antiglaucoma drugs: ocular vs systemic absorption. AB - In order to reduce the intraocular pressure antiglaucoma drugs must penetrate into the inner eye. Ocular bioavailability is determined by the ability of drug to penetrate through the cornea and conjunctiva/sclera, and on the other hand, by its elimination from the conjunctival sac. Major part of this elimination is by systemic drug absorption via conjunctiva. Typically conjunctival systemic absorption of drugs is an order of magnitude greater than their ocular absorption. In addition substantial systemic absorption of ophthalmic drugs takes place via nasal mucosa. Systemic absorption of antiglaucoma drugs like beta blocking agents may cause systemic side-effects. The risk of systemic side effects might be decreased by increasing the ocular/systemic ratio of drug absorption. Several approaches can be used to improve ocular/systemic drug absorption ratio. Firstly, corneal drug permeability is improved. This can be done using different formulations or prodrug derivatives. Secondly, systemic absorption can be decreased e.g. with kinetic drug interactions or drug formulations. Thirdly, the rate of drug delivery can be changed thereby affecting especially the peak concentrations of drug in systemic circulation. Different methods for improvement of ocular delivery relative to the systemic absorption of antiglaucoma drugs are summarized and the impact of systemic pharmacokinetics on the viability of each approach is discussed. PMID- 8207340 TI - Modulation of intraocular pressure by adenosine agonists. AB - Adenosine receptors have been shown to modulate a variety of physiological functions; however, little is known about the role these receptors play in the modulation of ocular function. To investigate the potential role of adenosine receptors in modulating intraocular pressure (IOP), the A1 agonist N6 cyclopentyladenosine (CPA), the nonselective adenosine agonist 5'-N ethylcarboxamideadenosine (NECA) and the A2 agonist 8-phenylaminoadenosine (CV 1808) were evaluated. Topical administration of NECA produced a dose-related reduction in IOP. However, an initial ocular hypertension of 1 to 2 hours was also observed in rabbits treated with NECA. The administration of CPA (165 micrograms) resulted only in a reduction in IOP, while the administration of CV 1808 produced only an initial ocular hypertension. As adenosine A1 receptors have been shown to be negatively coupled to adenylate cyclase in several systems, CPA was evaluated for its ability to suppress cAMP formation in the isolated iris/ciliary body. CPA produced a dose-related suppression of cAMP accumulation induced by 10(-6) M forskolin (EC50 = 3.2 nM). These results indicate that selected adenosine agonists can modulate IOP. The ocular hypotension induced by adenosine agonists is consistent with the activation of adenosine A1 receptors and may involve the modulation of cAMP levels in the iris/ciliary body. PMID- 8207341 TI - Treatment of glaucoma with 3 alpha, 5 beta-tetrahydrocortisol: a new therapeutic modality. AB - The effectiveness of 3 alpha, 5 beta-tetrahydrocortisol (3 alpha, 5 beta-THF), a metabolite of cortisol, in lowering intraocular pressure (IOP) in rabbits made ocular hypertensive with glucocorticoids suggested its use in patients with Primary Open Angle Glaucoma (POAG). Patients with well-documented POAG were treated with a 1% suspension of 3 alpha, 5 beta-THF administered to one eye four times daily for up to six weeks. Eight out of nine patients experienced an appreciable decrease in IOP in the treated eye (average decrease 4.9 mm Hg). There was no conjunctival irritation, corneal pathology, visual field changes, alteration in liver or renal function tests or blood count during the treatment period. The present study demonstrates that 3 alpha, 5 beta-THF, a naturally occurring steroid metabolite, is effective in lowering IOP in patients with POAG. Antiglucocorticoids may represent a new therapeutic modality for the management of POAG. PMID- 8207342 TI - Potential role of imidazoline (I1) receptors in modulating aqueous humor dynamics. AB - 1) Moxonidine (MOX), injected icvt into the anterior lateral ventricle of NZW rabbits, induced bilateral, ocular hypotension (> 7.0 mmHg) that persisted for two hrs. 2) Oxymetazoline (OXY), injected icvt into the anterior lateral ventricle of NZW rabbits, induced bilateral ocular hypotension (> 7.0 mmHg) that peaked at two hrs. 3) Unilateral topical application of OXY induced maximal, bilateral ocular hypotension (> 12 mmHg), at 3 hrs, in both the contralateral and ipsilateral eyes, that persisted more than 12 hrs. 4) The putative imidazoline (I1) antagonist, efaroxan, injected icvt into the anterior lateral ventricle, inhibited significantly the ocular hypotension produced by icvt MOX, icvt OXY, and unilateral topical OXY. 5) Imidazoline (I1) receptors, located in the CNS, play a role in MOX- and OXY-induced ocular hypotension, as suggested by the ability of the putative imidazoline (I1) receptor antagonist efaroxan, to inhibit icvt MOX-, icvt OXY- and topical OXY-induced ocular hypotension. PMID- 8207343 TI - A rationale for gene targeting in glaucoma therapy. AB - One of the mainstays of glaucoma treatment is the use of drugs that decrease the secretion of aqueous humor fluid from the ciliary epithelium. Unfortunately, many currently available drugs that decrease aqueous humor production such as beta adrenergic antagonists, may cause serious systemic side effects such as cardiac arrhythmias and arrest, pulmonary dysfunction, and CNS side effects such as decreased libido and depression. Efforts to develop effective aqueous suppressants that offer decreased morbidity and mortality in comparison to those currently available will likely rely on the ability to alter the function of specific cellular events which underlie aqueous humor production by the ciliary epithelium. However, the secretory process which results in aqueous humor production is incompletely understood and the identification of precise cellular mechanisms which underlie this process remain to be established. We will present a rationale for genetic approaches to regulate gene expression so that aqueous humor production may be specifically targeted in glaucoma patients. Techniques of gene transfer including homologous exchange recombination, and expression of antisense genes, will be discussed. PMID- 8207344 TI - In situ-forming gels for ophthalmic drug delivery. AB - Poor bioavailability of ophthalmic solutions caused by dilution and drainage from the eye can be overcome by using in situ-forming ophthalmic drug delivery systems prepared from polymers that exhibit reversible phase transitions. Joshi et al. (1), have demonstrated that aqueous compositions that reversibly gel in response to simultaneous variations in at least two physical parameters, such as temperature, pH, and ionic strength, can be formed by appropriate combinations of macromolecular polymers which exhibit reversible gelation properties. In the present study, the rheological characterization of such a system, prepared by a combination of Carbopol (C) and methyl cellulose (MC), was carried out at two different pH (4.0 and 7.4) and temperatures (25 and 37 degrees C) by rotational cone and plate viscometry. The shear stress (tau) vs. shear rate (D) flow curves of the aqueous polymer solutions indicated a pseudoplastic behavior, with a yield point. An increase in pH from 4.0 to 7.4, or temperature from 25 to 37 degrees C, resulted in an increase in viscosity (eta), tau, and yield point, the magnitude of changes being highest when both the parameters were altered simultaneously. An increase in concentration of either C or MC, or an increase in MC molecular weight results in an increase in eta, tau, and yield point. Among the compositions studied, a solution containing 1.5% MC 0.3% C was found to have low eta, and formed a strong gel under simulated physiological conditions. Such a system can be formulated as drug containing liquid suitable for administration by instillation into the eye, which upon exposure to physiological conditions will shift to the gel (semi-solid) phase, thus increasing the precorneal residence time of the delivery system and enhancing ocular bioavailability. PMID- 8207345 TI - Ion exchange resins for ophthalmic delivery. AB - A new novel delivery system for ophthalmic drugs was developed using an antiglaucoma agent Betaxolol Hydrochloride as a model. The new delivery system involved both the binding and release of drug from ion exchange resin particles. Betaxolol was studied in-vitro via a release model analysis. The ocular comfort of Betaxolol was greatly enhanced by reducing the availability of free drug molecules in the precorneal tear film. The amount of resin concentration was selected to obtain optimum binding of the drug. The zeta potential of suspended particles was adjusted to produce flocculated suspension. Drug resin particles were then incorporated into the structured vehicle, containing Carbomer 934P as a polymer, to enhance the physical stability and ease of resuspendability of the product. This delivery system also optimized the bioavailability of Betaxolol, reducing the total drug concentration in half to 0.25% Betaxolol in 0.25% BETOPTIC S Ophthalmic Suspension as compared with 0.5% Betaxolol in BETOPTIC 0.5% Sterile Ophthalmic Solution dosage form. Increased comfort of 0.25% BETOPTIC S Ophthalmic Suspension, as well as its bioequivalency data in animal models (rabbits), was confirmed in actual clinical trials of the product 0.25% BETOPTIC S Ophthalmic Suspension. The 0.25% BETOPTIC S Ophthalmic Suspension product has been approved gamma FDA and is marketed in U. S. since February 1990. The 0.25% BETOPTIC S Ophthalmic Suspension formulation has an increased bioavailability (equivalent to BETOPTIC 0.5% Sterile Ophthalmic Solution at half the concentration of drug); and pharmaceutically, is an elegant suspension product which settles slowly providing uniform dosage and increased ocular comfort. PMID- 8207346 TI - The role of iontophoresis in ocular drug delivery. AB - Iontophoresis has been utilized in the field of ophthalmology for many years. Present application of this technique has diminished considerably and few clinicians are currently familiar with its use. This review aims to educate the reader regarding the essential features of this procedure and to discuss the past and future role of iontophoresis in ocular drug delivery. PMID- 8207347 TI - Mucoadhesive ophthalmic vehicles: evaluation of polymeric low-viscosity formulations. AB - A series of polyanionic natural or semi-synthetic polymers (polygalacturonic acid, hyaluronic acid, carboxymethylamylose, carboxymethylchitin, chondroitin sulfate, heparan sulfate and mesoglycan) were evaluated as potential mucoadhesive carriers for ophthalmic drugs. Solutions containing cyclopentolate (CY) or pilocarpine (PI) as salts (or polyanionic complexes) with the acidic polymers, all showing a low viscosity, were tested for miotic (resp. mydriatic) activity in albino rabbits. In the case of some polymeric complexes, small but significant increases of the areas under the activity vs. time curves (AUC) over reference cyclopentolate hydrochloride (CYHC1) or pilocarpine nitrate (PINO3) vehicles, and significant AUC decreases after removal of precorneal mucin by treatment with N acetylcysteine were observed. A correlation was found between these data, considered indicative of the occurrence of a mucoadhesive interaction "in vivo", and "in vitro" viscometric data expressing the polymers-mucin force of interaction. The advantages and limitations of the mucoadhesive non-viscous approach in the formulation of ophthalmic vehicles are presented and discussed. PMID- 8207348 TI - Systemic delivery of polypeptide drugs through ocular route. AB - Because of rapid developments in biotechnology, numerous peptides are now available for clinical treatment of various diseases. In order to avoid parenteral injections, alternative routes of drug administration have been investigated. Among them, the ocular route seemed to be the most feasible one because a) it could deliver precise doses of drugs just like injections; b) it was much easier and less expensive to administer eyedrops than an injection; c) the rate of systemic absorption through the ocular route was as fast as an injection; d) eye tissues were much less sensitive to the development of immunological reactions than other tissues; e) the drug absorbed via the ocular route would avoid the first passage through hepatic circulation to reach the sites of action before liver metabolism; and f) no tolerance and ocular side effects could be detected after long-term (three months) daily administration of insulin eyedrops. PMID- 8207349 TI - Maintenance of multilocus variability under strong stabilizing selection. AB - We present exact conditions for stability of monomorphic equilibria in a general multilocus multiallele system and of specific polymorphic equilibria in general one- and two-locus multiallele systems. We show how these exact results on one- and two-locus systems can be used in approximate analysis of polymorphic equilibria in multilocus systems under selection strong relative to recombination. We determine conditions for existence and stability of polymorphic equilibria in specific models of quadratic stabilizing selection on additive polygenic traits. PMID- 8207350 TI - An eight-alternative concurrent schedule: foraging in a radial maze. AB - In two experiments conducted in an eight-arm radial maze, food pellets were delivered when a photocell beam was broken at the end of each arm via a nose poke, according to either fixed-interval or random-interval schedules of reinforcement, with each arm providing a different frequency of reinforcement. The behavior of rats exposed to these procedures was well described by the generalized matching law; that is, the relationships between log behavior ratios and log pellet ratios were approximated by linear functions. The slopes of these log-log functions, an index of sensitivity to reinforcement frequency, were greatest for nose pokes, intermediate for time spent in an arm, and least for arm entries. Similar results were obtained with both fixed-interval and random interval schedules. Addition of a 10-s changeover delay in both experiments eliminated the slope differentials between nose pokes and time spent in an arm by reducing the slopes of the nose-poke functions. These results suggest that different aspects of foraging may be differentially sensitive to reinforcement frequency. With concurrent fixed-interval schedules, the degree of temporal control exerted by individual fixed-interval schedules was directly related to reinforcement frequency. PMID- 8207352 TI - Effects of reinforcement history on responding under progressive-ratio schedules of reinforcement. AB - The effects of experimental history on responding under a progressive-ratio schedule of reinforcement were examined. Sixteen pigeons were divided into four equal groups. Groups 1 to 3 were trained to peck a key for food under a fixed ratio, variable-ratio, or differential-reinforcement-of-low-rate schedule of reinforcement. After training, these pigeons were shifted to a progressive-ratio schedule, later were shifted back to their original schedule (with decreased rates of reinforcement), and finally were returned to the progressive-ratio schedule. Pigeons in Group 4 (control) were maintained on the progressive-ratio schedule for the entire experiment. To test for potential "latent history" effects, pigeons responding under the progressive-ratio schedule were injected with d-amphetamine and given behavioral-momentum tests of prefeeding and extinction. Experimental histories affected responding in the immediate transition to the progressive-ratio schedule; response rates of pigeons with variable-ratio and fixed-ratio histories were higher than rates of pigeons with differential-reinforcement-of-low-rate and progressive-ratio-only histories. Pigeons with differential-reinforcement-of-low-rate histories, and to a lesser degree pigeons with variable-ratio and fixed-ratio histories, also had shorter postreinforcement pauses than pigeons with only a progressive-ratio history. No consistent long-term effects of prior contingencies on responding under the progressive-ratio schedule were evident. d-Amphetamine and resistance-to-change tests failed to reveal consistent latent history effects. The data suggest that history effects are sometimes transitory and not susceptible to latent influences. PMID- 8207351 TI - Choice in the time-left procedure and in concurrent chains with a time-left terminal link. AB - In two experiments, rats chose between a standard fixed-duration food-associated stimulus and a stimulus whose duration was the time remaining to reinforcement in an elapsing comparison interval. In Experiment 1, 4 rats responded in a time-left procedure wherein a single initial-link variable-interval schedule set up two potential terminal links simultaneously. As time elapsed in the initial-link schedule, the choice was between a standard fixed-interval 30-s terminal link and a time-left terminal link whose programmed interval requirement equaled 90 s minus the elapsed time in the initial link. Rats generally responded more on the lever with the shortest programmed terminal-link duration, but the temporal parameters of the procedure were found to vary with response distributions. Contrary to previous reports, therefore, time-left data were well predicted by choice models that make no assumptions about animal timing. In Experiment 2, 8 rats responded on a concurrent-chains schedule with independent variable-interval initial links and a time-left terminal link in one of the choice schedules. On the time-left lever, the programmed terminal-link delay equaled 90 s minus the elapsed time in the time-left initial link. On the standard lever, terminal-link responses were reinforced according to a variable-interval schedule whose average value varied over four conditions. Relative time-left initial-link responses increased in the elapsing time-left initial-link schedule as the time-left terminal link became shorter relative to the standard terminal link. Scalar expectancy theory failed to predict the resultant data, but a modified version of the delay-reduction model made good predictions. An analysis of the elaboration of scalar expectancy theory for variable delays demonstrated that the model is poorly formulated for arithmetically distributed delays. PMID- 8207353 TI - Human choice in concurrent ratio-interval schedules of reinforcement. AB - Seven undergraduates participated in a concurrent-choice experiment with monetary reinforcers. Response-independent analogues of variable-interval and variable ratio schedules were used to assess whether subjects would maximize reinforcement rate. The optimal pattern of behavior, in terms of maximizing reinforcement rate, involved a large bias toward the ratio alternative, with only occasional sampling of the interval schedule. Most experiments with pigeons, however, demonstrate matching of response rates to reinforcement rates, with only slight biases for the ratio schedule. Although subjects in the present experiment allocated more time to the ratio alternative than required by matching, the magnitude of the bias did not approximate that predicted by a maximizing account. After exposure to clock stimuli correlated with the operation of each schedule, 1 subject's behavior did show a substantial level of bias, increasing the total number of reinforcers obtained, and lay at a point between the predictions of matching and maximizing. The other subjects, however, continued to respond less optimally. The present results can be accounted for by a view of matching that incorporates the effects of delayed reinforcement. PMID- 8207354 TI - Delay reduction and optimal foraging: variable-ratio search in a foraging analogue. AB - The present study investigated conditions under which the conditioned reinforcement principles of delay-reduction theory and views based on simple maximization of reinforcement rate make ordinally opposing predictions with respect to foraging-related choice behavior. The use of variable-ratio schedules in the choice phase also represents an extension of delay-reduction theory to schedules that may better mimic the effort involved in searching. Pigeons responded on modified concurrent-chains schedules in which equal variable-ratio schedules led to unequal variable-interval outcomes and unequal reinforcer amounts. All 4 subjects completed a minimum of two replications of conditions for which the predictions of delay-reduction theory and a simple rate-maximizing theory were opposed. Results were consistent with delay reduction's ordinal predictions in 11 of 11 replications of the divergent predictions favoring the smaller, more immediate alternative. The predictions of rate maximization were upheld only when they were consistent with those of delay reduction. Results are discussed in terms of conditioned reinforcement, sensitivity to reductions in delay to food, and possible rules of thumb that may be useful in characterizing foraging. PMID- 8207355 TI - Effects of chlordiazepoxide and cocaine on concurrent food and avoidance-of timeout schedules. AB - Five rats were trained on a concurrent schedule in which responses on one lever produced a food pellet on a random-interval 30-s schedule during 10 s of food availability associated with distinctive exteroceptive stimuli. Responses on another lever postponed for 20 s the presentation of a 50-s timeout, during which all stimuli were extinguished and the schedule contingencies on the food lever were suspended. The response rates maintained by the random-interval schedule exceeded those maintained by the avoidance contingency, but both provided a stable baseline to assess the behavioral effects of different drugs. Low doses of cocaine hydrochloride (1 and 3 mg/kg) did not affect food-reinforced responding or avoidance response rates. Intermediate doses (5.6, 10, and 13 mg/kg) produced a dose-dependent decrease in food-maintained and avoidance response rates, and both types of responding were virtually eliminated after administration of the highest doses (17 and 30 mg/kg) of cocaine. Low doses of chlordiazepoxide (1 and 3 mg/kg) increased food-maintained and avoidance response rates, and both rates decreased systematically after 10 and 30 mg/kg of this drug. The effects of cocaine and chlordiazepoxide on response rates maintained by avoidance of timeout from food presentation were unlike those reported when subjects responded to avoid shock presentation. The results of this experiment thus provide evidence to suggest that the effects of drug administration on avoidance behavior may be a function of the nature of the consequent event to be avoided. PMID- 8207356 TI - Transfer of relational stimulus control in conditional discriminations. AB - Four adults were trained, using instructions and a matching-to-sample procedure, to select Stimulus B1 in the presence of Stimulus A1, B2 in the presence of A2, and B3 in the presence of A3 (the AB relations). Analogous PQ relations were trained. Afterwards, one stimulus in Set A and another stimulus in Set B appeared together as a sample, and novel Stimuli X1 and X2 were the comparisons. Responses to X1 were reinforced if the two stimuli in the sample had been related in the previous training (e.g., A1 and B1), and responses to X2 were reinforced if the two samples had not been related (e.g., A1 and B2). These were the ABX relations. In a test in which a stimulus of Set P and another of Set Q were the samples and X1 and X2 were the comparisons, 2 subjects selected X1 when the samples were P1 and Q1, P2 and Q2, and P3 and Q3, and selected X2 in the presence of the other six sample combinations (P1Q2, P1Q3, P2Q1, P2Q3, P3Q1, and P3Q2). Another subject showed the same responding after additional training. In the second experiment, 3 adults and an 11-year-old child were trained on AB, PQ, and ABX relations, and they showed the symmetrical relations BA and QP upon testing. Then all 4 of these subjects responded accurately to the PQX test. Results of Experiments 1 and 2 showed novel, consistent comparison selection based on the previously established relation between the two stimuli in the sample. In a third experiment, 3 of the subjects who had shown PQX relations were trained on EFX relations, with pairs of E and F stimuli as samples and X stimuli as comparisons. When the EF relations were tested, all 3 subjects consistently selected F1 in the presence of E1, F2 in the presence of E2, and F3 in the presence of E3 from the first trial. The results of Experiment 3 showed novel stimulus relations after training with a more complex conditional discrimination format. PMID- 8207357 TI - Dissecting the conditioned pecking response: an integrated system for the analysis of pecking response parameters. AB - The conventional pecking response key, although an excellent transducer of response rate, can provide minimal information on the topography, coordination, or localization of conditioned pecking. We describe the hardware and software components of a system that, in addition to recording response rates, permits simultaneous "on-line" monitoring of head acceleration, jaw movement, terminal peck location, and duration of pecking response. Head movements are monitored with a miniature accelerometer, jaw movements with a magnetosensitive transducer, and peck location with modified touch screen technology. Initial experiments with the system suggest that it will be useful in studies of response differentiation, acquisition and maintenance of complex discriminations, and interaction of conditioned and unconditioned stimuli in the control of pecking response probability and response topography. PMID- 8207358 TI - Minisymposium: the natriuretic peptide hormones. Introduction. Editorial and historical review. PMID- 8207359 TI - The natriuretic peptides in heart failure. PMID- 8207360 TI - Physiology of natriuretic peptides. PMID- 8207361 TI - The natriuretic peptides and hypertension. PMID- 8207362 TI - Biochemistry of natriuretic peptides. PMID- 8207363 TI - Stopping antihypertensive drug therapy in elderly people--a dangerous experiment? PMID- 8207364 TI - A 5-year prospective, observational study of the withdrawal of antihypertensive treatment in elderly people. AB - OBJECTIVES: To observe blood pressure, cardiovascular events, and total mortality after withdrawing antihypertensive treatment for elderly patients. DESIGN: Multicentre observational study. SETTING: Sweden. A 5-year follow-up of 333 elderly hypertensive patients, aged 70-84 years (mean age 75.2 +/- SD 3.8 years, 68% females). In all, 74 out of the 333 patients (22%) died during the study period. METHOD: After withdrawal of the antihypertensive therapy, all patients started in the untreated state and during the 5-year follow-up they could then either remain in the untreated state, or be reverted to blood-pressure-lowering drug treatment because of hypertension or other diseases, e.g. angina pectoris, oedema, congestive heart failure, etc. RESULTS: The probability of remaining without treatment for 5 years was estimated to be 20%. During the state of no treatment the patients had a lower total mortality risk than that of the general Swedish population, matched for age and sex. They also had a lower risk of cardiovascular events than those in the treated states. Markers indicating a successful withdrawal were monotherapy in low doses and relatively low blood pressure before withdrawal. CONCLUSION: These results suggest that with frequent check-ups, withdrawal of antihypertensive therapy in the elderly can be tried without increased risk of cardiovascular events. PMID- 8207365 TI - The personality patterns in patients with duodenal ulcer and ulcer-like dyspepsia and their relationship to the course of the diseases. Hvidovre Ulcer Project Group. AB - OBJECTIVES: To compare personality characteristics in duodenal ulcer patients and patients with ulcer-like dyspepsia from the primary health sector with duodenal ulcer patients from a hospital and to evaluate the relationship of the personality characteristics to the course of the diseases. DESIGN: A prospective study using the Minnesota Multiphasic Personality Inventory (MMPI) with retesting of a subgroup of patients after a median observation period of 14 months. SETTING: Departments of Medical and Surgical Gastroenterology, Hvidovre University Hospital, and the primary health sector in Roskilde County, Denmark. SUBJECTS: Sixty hospital patients with duodenal ulceration and 17 patients with duodenal ulceration plus 25 patients with ulcer-like dyspepsia from the primary health sector. MAIN OUTCOME MEASURES: MMPI scores. RESULTS: The hospital patients differed from the two other groups of patients by having higher scores of depression and anxiety (P < 0.05). Twenty-eight of the patients were retested with MMPI. Contrary to the patients with persisting complaints, abnormal personality characteristics disappeared in patients without complaints (P < 0.05 0.001). CONCLUSIONS: The results indicate that abnormal personality characteristics in patients with functional and organic upper dyspepsia are consequential rather than causal factors. PMID- 8207366 TI - Relationships between plasma levels of catecholamines and neuropeptides and the survival time in patients with congestive heart failure. AB - OBJECTIVES: To evaluate the importance of various variables reflecting neuroendocrine activation in relation to prognosis in patients with congestive heart failure (CHF). DESIGN: Plasma levels of noradrenaline, adrenaline, neuropeptide Y, substance P, calcitonin gene-related peptide, vasopressin and atrial natriuretic peptide were measured in patients presenting with CHF and related to survival time. Survival time was calculated from the time-point of this investigation until the month when the patient died or until December 1992. The follow-up period ranged up to 60 months. Seven of the 31 patients were still alive at the end of this period. SETTING: Lund University Hospital, Sweden. SUBJECTS: Thirty-one patients with CHF due to ischaemic heart disease. Six patients had a degree of heart failure corresponding to NYHA I-II and 25 corresponding to NYHA III-IV. Ten of these 25 patients were on angiotensin converting enzyme (ACE) inhibition in addition to therapy with digoxin and diuretics. The catecholamine and neuropeptide levels were compared to those of a control group of 31 healthy subjects aged 20-80 years. INTERVENTION: There were not any specific intervention in addition to the treatment for heart failure as outlined above. MAIN OUTCOME MEASURES: Survival time until death from heart disease or until the end of the follow up period in December 1992. RESULTS: There were inverse relationships between survival time on one hand and plasma values of noradrenaline (r = -0.49; P < 0.01) and atrial natriuretic peptide (r = -0.49; P < 0.01) on the other hand. There was a significant correlation between the plasma values of noradrenaline and atrial natriuretic peptide (r = 0.50; P < 0.01). CONCLUSION: Increased plasma levels of noradrenaline and atrial natriuretic peptide are of major importance as prognostic markers in patients with CHF. PMID- 8207367 TI - The relationship of fasting insulin levels to vascular risk factors in a general practice in Northern Ireland. AB - OBJECTIVE: To investigate the relationship between insulin and vascular risk factors in a healthy male population at high risk of ischaemic heart disease. DESIGN: Computer-generated random number selection of subjects. SETTING: A suburban general practice population (total practice population 4500) in Northern Ireland. SUBJECTS: Four hundred male subjects, aged 35-65 years, were randomly selected with 273 responding. INTERVENTION: At interview, each subject completed a questionnaire, had blood pressure measured and a 12-lead ECG recorded. The next morning, fasting blood samples were taken and a timed overnight urine collection for the albumin excretion rate was returned. RESULTS: To exclude the confounding effects of other variables on insulin concentrations, a healthy nonobese, nondiabetic, normotensive group with no history of ischaemic heart disease, no family history of diabetes and not taking drugs was identified (n = 120). Within this group there was a significant correlation between insulin and triglyceride (r = 0.30; P < 0.05), high-density lipoprotein (HDL) cholesterol (r = 0.24; P < 0.05) and glucose (r = 0.30; P < 0.05). A group with higher insulin levels (n = 22) were compared to a group with lower insulin levels (n = 22). Serum triglyceride was higher (1.29 +/- 0.1 vs. 1.00 +/- 0.08 mmol L-1; P < 0.05), HDL cholesterol was lower (1.26 +/- 0.06 vs. 1.50 +/- 0.09 mmol L-1; P < 0.05) and plasma glucose higher (5.2 +/- 0.1 vs. 4.9 +/- 0.1 mmol L-1; P < 0.05) in the group with higher insulin levels. CONCLUSIONS: There is a relationship between insulin and triglyceride, HDL cholesterol and glucose but not blood pressure, cholesterol or low-density-lipoprotein (LDL) cholesterol in a healthy population at high risk of ischaemic heart disease. PMID- 8207368 TI - Paralytic ileus as a result of diltiazem treatment. AB - Diltiazem is a widely used calcium channel blocker, and has been found to be effective in the treatment of hypertension, stable, variant and unstable angina, as well as oesophageal spasm. Calcium channel antagonists have been shown to diminish the contractility of gut smooth muscle, but have not as yet been reported to cause clinically significant inhibition of gut motility when used alone. We report a case of reversible functional intestinal obstruction, immediately following diltiazem treatment in a patient with ischaemic heart disease. PMID- 8207369 TI - Membranous obstruction of the inferior vena cava. PMID- 8207370 TI - Perceptual specificity of auditory priming: implicit memory for voice intonation and fundamental frequency. AB - Five experiments explored the effect of acoustic changes between study and test on implicit and explicit memory for spoken words. Study-test changes in the speaker's voice, intonation, and fundamental frequency produced significant impairments of auditory priming on implicit tests of auditory identification and stem completion but had little or no effect on explicit recall and recognition tests (Experiments 1-4). However, study-test changes in overall decibel level had no effect on priming on an auditory stem-completion test or on cued-recall performance (Experiment 5). The results are consistent with the idea that fundamental frequency information is represented in a perceptual representation system that plays an important role in auditory priming. PMID- 8207371 TI - Does implicit memory extend to legal and illegal nonwords? AB - In 4 experiments, implicit and explicit memory for words and nonwords were compared. In Experiments 1-2 memory for words and legal nonwords (e.g., kers) was assessed with an identification (implicit) and a recognition (explicit) memory task: Robust priming was obtained for both words and nonwords, and the priming effects dissociated from explicit memory following a levels-of-processing manipulation (Experiment 1) and following a study-test modality shift (Experiment 2). In Experiment 3, priming for legal and illegal nonwords (e.g., xyks) was observed on an identification task, and the effects dissociated from explicit memory following a levels-of-processing manipulation. Finally, in Experiment 4, significant inhibitory priming for legal nonwords was observed when a lexical decision task was used. Results suggest that implicit memory can extend to legal and illegal nonwords. Implications for theories of implicit memory are discussed. PMID- 8207372 TI - Attention mechanisms mediate the syntactic priming effect in auditory word identification. AB - The syntactic priming effect and the involvement of attention in that process were investigated by testing identification of white noise-masked Hebrew words. Targets were either syntactically congruent or syntactically incongruent with the structure of the sentence. Relative to a neutral condition, similar facilitation and inhibition was found for congruent and incongruent targets, respectively. When syntactic congruency was blocked, the inhibition was attenuated, whereas the facilitation remained the same. A 350-ms silent interstimulus interval between context and target increased inhibition without affecting facilitation. We suggest that both the facilitation and the inhibition effects of syntactic priming are based on a veiled controlled process of generating expectations. The inhibition results from a controlled process of reevaluation that requires additional attention resources. PMID- 8207373 TI - Neighborhood effects in visual word recognition: effects of letter delay and nonword context difficulty. AB - The role of a target's orthographic neighborhood in visual word recognition was investigated in 2 lexical decision experiments. In both experiments, some stimuli had 1 letter delayed relative to the presentation of the rest of the stimulus. Experiment 1 showed that delaying a letter position, which yielded a potentially competitive neighbor, was more costly to target recognition than delaying a position that yielded no neighbors. This effect was strongest when one of these neighbors was of higher frequency than the target itself. Additionally, the effect was reduced for words with a high friendly-to-unfriendly-neighbor ratio (friendly neighbors being those words containing the delayed letter). In Experiment 2 the difficulty of the word-nonword discrimination was manipulated by varying the density of the nonwords' neighborhoods. Only when the nonwords had many neighbors at several positions did the word responses show neighborhood competition effects. PMID- 8207374 TI - Transsaccadic integration of biological motion. AB - In a transsaccadic integration paradigm, Ss had to detect saccade-contingent changes in a moving point-light walker. First, the nature of the object representation surviving a saccade was examined. The low detection of changes in the image-plane position of the figure and the high detection of changes in the upright walker's in-depth orientation indicated that transsaccadic object representations are position invariant but orientation dependent. Implications for object recognition are highlighted. The second issue concerned transsaccadic anticipation of the future event course. Ss anticipated the postsaccadic relative positions of the walker's body parts. In contrast, there was no anticipation of the postsaccadic absolute position of a translating figure; instead, Ss relied on memory of the figure's presaccadic position. The anticipated in-depth orientation of a rotating walker seemed to be distorted in the direction of canonical views. PMID- 8207375 TI - Effects of level of processing on implicit and explicit tasks. AB - The series of experiments presented in this article replicate the interaction that B. H. Challis and D. R. Brodbeck (1992) reported between list design (blocked or mixed) and level of processing for word fragment completion: The advantage for semantically processed words over shallowly processed words was greater when the conditions were blocked than when they were mixed on the study list. A similar interaction was found for perceptual identification (a data driven implicit task) and priming in general knowledge questions (a conceptually driven implicit task). However, both data-driven and conceptually driven explicit tasks failed to reveal such a pattern. PMID- 8207376 TI - Do ability-performance relationships differentiate age and practice effects in visual search? AB - Relationships between abilities and performance in visual search were investigated for young and old adults. Ss received extensive practice on category search task. A consistent version allowed development of an automatic attention response; a varied version allowed general performance improvements. Transfer conditions assessed learning. General ability, induction, semantic knowledge, working memory, perceptual speed, semantic memory access, and psychomotor speed were assessed. LISREL models revealed that general ability and semantic memory access predicted initial performance for both ages. Improvements on both the consistent and varied tasks were predicted by perceptual speed. Ability performance relationships indexed performance changes but were not predictive of learning (i.e., automatic process vs. general efficiency). Qualitative differences in the ability-transfer models suggest age differences in learning. PMID- 8207377 TI - Role of elaborative and perceptual integrative processes in perceptual-motor performance. AB - Three experiments address the dependence of both explicit and implicit memory performance on elaborative processes for a perceptual-motor task, pursuit rotor. Explicit memory performance was reflected by recognition of previously encountered pursuit rotor stimuli. Implicit memory performance (priming) was identified in Experiment 1 as an advantage in pursuit rotor performance for old stimuli that Ss failed to explicitly recognize. In Experiments 2 and 3, the types of strategies that Ss engaged in during training and test phases were manipulated. Results indicated that explicit memory performance depended on elaborative processes that emphasized which specific stimuli were encountered, whereas reliable implicit memory performance appeared only under a control no instruction condition. Discussion focuses on attention to perceptual-integrative processes for priming. PMID- 8207378 TI - Insulin but not progesterone promotes the biosynthesis of glycogen in Xenopus laevis oocytes: implications on the control of glycogen synthase by phosphorylation, dephosphorylation. AB - Insulin, the well-known hypoglycemic hormone, mimics progesterone in promoting the resumption of meiosis within the oocyte of Xenopus laevis. Both hormones exert their action through the inhibition of protein kinases and the activation of protein phosphatases. Because glycogen synthase is an enzyme regulated by a kinases/phosphatases cascade, we investigated the effect of insulin and progesterone on the regulation of glycogen synthesis and glycogen synthase throughout the oogenesis of Xenopus laevis oocytes. In this framework the maximal activity of synthase "a" is concomitant with the vitellogenic period characterized by a drastic increase in the amount of glycogen. Oocyte glycogen synthase is inhibited by cAMP-dependent phosphorylation and stimulated by 20 mM Mg2+. The magnesium effect is inhibited by mu molar concentrations of okadaic acid and suggests that oocyte glycogen synthase is activated by dephosphorylation achieved by protein phosphatase-1. The okadaic acid effect is itself thwarted by the specific inhibitor of protein kinase A, confirming the role of this kinase in the regulation of glycogen synthase. Finally, working on intact ripe oocytes, we showed that insulin but not progesterone increases glycogen synthesis and glycogen synthase "a" activity and lowers the rates of phosphorylation, especially in the glycogen-bound proteins. PMID- 8207379 TI - The pseudoblastema in the wound healing process of the leech Hirudo medicinalis L. (Hirudinea): changes in cell junctions. AB - The role of the connective tissue cells and their migratory behavior have been investigated in the formation and evolution of the pseudoblastema during wound healing in the leech Hirudo medicinalis. In H. medicinalis the healing process shows first a flow of cells that effectively seal the wound and form a temporary cellular clump, the pseudoblastema, which contributes to the phagocytotic process and apparently regenerates the extracellular matrix. The migratory cells forming the pseudoblastema are connective tissue cells known as vasocentral cells, which, when in a resting state, are associated with the vasofibrous cells. During the formation and evolution of the pseudoblastema several changes affect vasocentral cell junctions. At rest, vasocentral cells do not show cell to cell junctions but they show adhering junctions in contact with the extracellular matrix. These junctions disrupt during the migratory phase. When vasocentral cells regroup in the pseudoblastema, adhering junctions are formed between them, and adhering junctions making contact with the matrix appear again. As the pseudoblastema evolves, cell to cell adhering junctions become more conspicuous and undergo other changes. During the next stage of retraction, close contacts develop between pseudoblastema cells and neighboring nondamaged muscle fibers, which probably serve as points of anchorage for the approaching movement of the wound edges. Finally, cell to cell and cell to matrix junctions disappear and the pseudoblastema disintegrates. PMID- 8207380 TI - Pedicle and antler regeneration following antlerogenic tissue removal in red deer (Cervus elaphus). AB - The physiological control mechanisms underlying the histogenesis of the pedicle, which precedes antler growth, from the frontal bones of male deer are poorly understood. The aim of this study was to investigate the extent of pedicle/antler regeneration after removal (for histological evaluation) of the antlerogenic region or pedicle tissue during pedicle development to determine whether the subsequent pattern of regeneration could contribute to the understanding of pedicle histogenesis and the mechanism of the transition between permanent pedicles and deciduous antlers. The contralateral pedicles of six stags were not removed and these data serve as controls. All deer were observed frequently and measurements of regeneration were made in March after all antler growth had ceased for that season. The development stage of the pedicle was determined by a combination of pedicle height measurements and histological studies. The results showed that pedicle formation histologically covers three stages: a period of intramembranous ossification (when the pedicle is less than 5 mm in height), a period when the ossification pattern changes (when the pedicle is between 5 and 28 mm in height) and a period of modified endochondral ossification (when the pedicle is over 30 mm in height). In all ossification stages some deer regenerated neither antlers nor pedicles. The pedicles which regenerated following the loss of antlerogenic tissue at the intramembranous ossification stage were shorter than the controls (P < 0.01), but longer than the pedicles regenerated after pedicle removal at the transitional stage in the pattern of ossification (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207381 TI - Oocyte recovery and maturation in the American black bear (Ursus americanus): a model for endangered ursids. AB - A study was conducted to determine if meiotic maturation could be induced in ovarian oocytes of the American black bear (Ursus americanus), a model for gamete "rescue" techniques for endangered ursids. Ovaries obtained from 48 black bears yielded 2,403 oocytes (51.1 +/- 4.9/female), of which 777 (32.3%) were morphologically classified as excellent quality. More total oocytes were recovered from donors that were anestrous compared to luteal/pregnant (P < 0.05) at the time of ovarian excision. Delaying the recovery of oocytes from antral follicles within excised ovaries from 12-24 hr to 25-36 hr had no effect (P > 0.05) on the overall number of high quality oocytes recovered or subsequent maturational ability. The highest incidence of metaphase II was reached between 48 and 60 hr of in vitro incubation. Donor status (anestrous vs. luteal/pregnant) had no influence on the oocyte maturation rate by 24 or 48 hr, but by 60 hr, more (P < 0.05) oocytes recovered from anestrous females (43.9%) had achieved metaphase II compared to luteal/pregnant counterparts (23.1%). In preliminary trials involving endangered ursids, 54 ovarian oocytes were recovered from three aged sun bears (Helarctos malayanus), of which 72.2% were excellent quality and 15.4% matured in vitro to metaphase II. Similarly, 119 antral oocytes were recovered from two aged sloth bears (Melursus ursinus), of which 41.2% were excellent and 17.5% matured in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207382 TI - Rapid induction of a hyperciliated phenotype in zinc-arrested sea urchin embryos by theophylline. AB - Zinc ions, present since fertilization, will arrest embryos of the sea urchin Tripneustes gratilla at the hatched blastula stage, but such embryos lack long cilia, the usual characteristic of animalized embryos. Eventually these embryos will express a minimal long cilia phenotype, with a mean population < 1.4 times that of control blastulae, but only after contemporaneous control embryos gastrulate. Theophylline will rapidly but minimally animalize embryos when added after hatching, but its inductive ability decreases as the embryos gastrulate. Theophylline-animalized embryos produce cilia whose mean population length is > 1.5 times that of control blastulae. At any point from the time of hatching up until control complete gastrulation, theophylline added to zinc-arrested embryos will induce a hyperciliated phenotype with a mean population length nearly 3 times that of control blastulae. The elongation of cilia is immediate and significantly exceeds the rate of normal ciliary regeneration. Initially requiring the presence of theophylline, the hyperciliated phenotype becomes stable as control embryos begin gastrulation and, when deciliated, the induced embryos will regenerate hyperlong cilia in the absence of theophylline. The time dependence for both induction and phenotype stability would suggest that certain timing mechanisms are still operative in zinc-arrested embryos. This inducible system should facilitate studies of length control during ciliary elongation and regeneration. PMID- 8207383 TI - Embryonic expression pattern of amyloid protein precursor suggests a role in differentiation of specific subsets of neurons. AB - Immunohistochemical analysis revealed the temporal and spatial expression pattern of the amyloid protein precursor (APP) during the development of the mouse embryo. APP was first detected at day 9.5 of gestation in motor neurons of the hind brain and the spinal cord. APP proteins were also evident in cells of the floor plate, and in neurons of the cranial, dorsal root, and sympathetic ganglia shortly after their formation. Except for floor plate cells, APP expression was restricted to differentiated neurons. Comparison with the expression of microtubule-associated protein 2 (MAP-2), a marker for neurodifferentiation, showed that APP is expressed on a subset of differentiated neurons. APP can also serve as an early marker for the developing nuclei of the hind brain. The onset of APP expression in neurons appeared to be correlated with axonal outgrowth, whereas later expression of APP may be associated with functional specialization in the developing nervous system. PMID- 8207384 TI - Morphological and functional changes accompanying the acquisition of meiotic competence in ovarian goat oocyte. AB - In order to determine at which follicular size goat oocytes were capable of resuming and completing meiosis, we evaluated their ability to mature in vitro and measured their maturation promoting factor (MPF) activity by histone H1 kinase assay. The results indicated that goat oocyte meiotic competence developed progressively in follicles ranging from 0.5 to 3 mm; the oocytes acquired the ability to resume meiosis in follicles of 0.5-0.8 mm, to reach metaphase I (MI) in follicles of 1-1.8 mm, and to reach metaphase II (MII) in follicles larger than 3 mm. The presence of MPF activity was first observed in oocytes arrested at early prometaphase I and reached a maximum level in oocytes blocked in metaphase I (MI). In the second part of this study, RNA synthesis and nucleolar changes were analyzed during the growth period. The acquisition of meiotic competence was accompanied by nucleolar compaction and a dramatic decrease in RNA synthesis. Changes in protein patterns were also analyzed, but only slight differences were observed among oocytes from the different classes. PMID- 8207385 TI - Mouse trophoblast cell invasion of extracellular matrix purified from endometrial tissue: a model for peri-implantation development. AB - We have investigated the invasive activity of mouse trophoblast cells during embryo implantation in vitro by culturing blastocysts with extracellular matrix (ECM) purified from mouse endometrium obtained on day 4 of pregnancy. Endometrium was dissected from lyophilized mouse uteri, and intact ECM was isolated by sequential precipitation in nonionic detergent and high salt. Electron microscopic examination of the ECM revealed typical collagen fibers plus an amorphous material resembling basement membrane. Electrophoretic analysis of the ECM revealed an enrichment of high molecular weight proteins, and immunoblotting indicated the presence of fibronectin, laminin, entactin, and type IV collagen, but not the intracellular proteins 2',3'-cyclic nucleotide-3'-phosphodiesterase or vimentin. Mouse blastocysts cultured with this ECM attached to it within 3 days, and the trophoblast cells began to migrate through the matrix in a manner resembling trophoblast invasion in utero. Unlike blastocysts cultured on plastic surfaces, the trophoblast did not flatten and become disorganized, but retained a polarized, spherical structure. Fluorescent microscopy with fluorescein isothiocyanate-labeled phalloidin revealed a high degree of microfilament organization and established that actin was absent from the ECM preparation. In the presence of a serum substitute, differentiation continued through yolk sac formation. Without serum components, yolk sac did not form; however, light and electron microscopic examination indicated that the invasive behavior of trophoblast cells persisted and was comparable to that of trophoblasts cultured in the presence of the serum substitute. A three-dimensional model for investigating trophoblast behavior in ECM from the endometrium should be of great value in elucidating the cellular and molecular events surrounding the process of blastocyst implantation. PMID- 8207386 TI - Purification and characterization of m-calpain from the skeletal muscle of the amphibian Rana ridibunda. AB - Calpain was purified to apparent homogeneity from the skeletal muscle of the amphibian Rana ridibunda. It is composed of two subunits of 78 and 28 kDa, respectively. The enzyme exhibits kinetic properties similar to those of mammalian and avian skeletal muscle m-calpains. Ca2+ requirements for half and maximum activities are 400 microM and 1.5 mM, respectively. It is strongly inhibited by thiol protease inhibitors such as leupeptin, E-64, and antipain and by alkylating thiol group agents such as iodoacetic acid (IAA), iodoacetamide (IAM), and N-ethylmaleimide (NEM). Its activity is enhanced by reduced thiols such as dithiothreitol (DTT), cysteine, and 2-mercaptoethanol. The enzyme is stable in the absence of Ca2+ at 55 degrees C, it displays maximum activity at 25 degrees C, and it shows a broad pH optimum between 6.5 and 7.8. In the absence of Ca2+, various divalent cations such as Sr2+, Mn2+, and Ba2+ strongly activate, while other divalent cations such as Ni2+, Co2+, Cd2+, Zn2+, and Cu2+ have no effect on its activity. In the presence of Ca2+, the cations Sr2+, Mn2+, and Ba2+ show a synergistic effect, while the cations of the other group strongly inhibit the calpain activity. The above data demonstrate that calpain from the skeletal muscle of the amphibian Rana ridibunda is a neutral, Ca(2+)-activated thiol protease and that it belongs to the class of m-calpains. PMID- 8207387 TI - Herpes simplex virus type 1 DNA persistence, progressive disease and transgenic immediate early gene promoter activity in chronic corneal infections in mice. AB - We have used a mouse model system and the corneal route of inoculation to examine the issue of extra-neuronal persistence of herpes simplex virus type 1 (HSV-1). HSV-1 strain F DNA and inflammatory lesions were detected in corneal tissue of mice at 5, 11, 23, 37 and 60 days post-infection (p.i.) Viral DNA was localized by in situ PCR to epithelial cells and less frequently to cells in the stroma of the cornea. Viral proteins were not detected in the cornea and virus could not be isolated from tissue homogenates after 11 days p.i. even though histopathological lesions became progressively more severe at 37 and 60 days p.i. The DNA containing cells were usually adjacent to the sites of inflammation or within these sites in the chronic stage (23, 37 and 60 days p.i.). In contrast to strain F, persistence of HSV-1 strain KOS DNA and inflammatory lesions were not detected after 11 days p.i.; this result suggests that the long-term persistence of HSV-1 DNA and the development of inflammatory lesions are virus strain-dependent. We tested for the possibility of transgenic HSV-1 immediate early gene (ICP4) promoter activity in chronically infected corneas of transgenic mice containing the ICP4 promoter fused to the bacterial beta-galactosidase coding sequence. Our results indicated that the chimeric transgene was expressed in the cornea at 5, 11, 23, 37 and 41 days p.i. Possible explanations for these results and mechanisms for the generation of the chronic inflammatory lesions are discussed. The properties of chronic HSV infections in the cornea may be similar to those which have been described for persistent or defective viral infections in other systems. PMID- 8207388 TI - Glycoprotein C-independent binding of herpes simplex virus to cells requires cell surface heparan sulphate and glycoprotein B. AB - Previous studies have shown that the initial interaction of herpes simplex virus (HSV) with cells is binding to heparan sulphate and that HSV-1 glycoprotein C (gC) is principally responsible for this binding. Although gC-negative viral mutants are impaired for binding and entry, they retain significant infectivity. The purpose of the studies reported here was to explore the requirements for infectivity of gC-negative HSV-1 mutants. We found that absence or alteration of cell surface heparan sulphate significantly reduced the binding of gC-negative mutant virus and rendered cells resistant to infection, as shown previously for the wild-type virus. We isolated a recombinant double-mutated HSV strain that produces virions devoid of both of the known heparin-binding glycoproteins, gB and gC. The drastically impaired binding of these mutant virions to cells, relative to gC-negative and wild-type virions, indicates that gB mediates the binding of gC-negative virions to cells. Thus at least two HSV glycoproteins can independently mediate the binding of HSV to cell surface heparan sulphate to start the process of viral entry into cells. PMID- 8207389 TI - The nuclear location of PML, a cellular member of the C3HC4 zinc-binding domain protein family, is rearranged during herpes simplex virus infection by the C3HC4 viral protein ICP0. AB - ND10 are nuclear domains of unknown function that become abundant in response to stress. Infection by herpes simplex virus type 1 (HSV-1) causes the apparent disappearance of these domains, an effect that requires the expression of the immediate early protein ICP0. Previously, we have shown that there are a number of cellular antigens in the ND10. In this report, we show that one of these proteins is PML, a member of the C3HC4 zinc-binding domain family which also includes ICP0. The C3HC4 domain of ICP0 is essential for the apparent release of PML from the ND10, although the interaction of ICP0 with ND10 is determined by a small region near its carboxy terminus. PML and other ND10 proteins are not lost after removal from ND10 but deposited at the nuclear envelope or nuclear envelope modifications during later parts of the replication cycle. ICP0 is required for the onset of low multiplicity infections, and has been implicated in the process of reactivation from HSV latency. Therefore, the interaction between ICP0 and the ND10 domains, specifically PML, may be important for the outcome of virus-cell interactions. PMID- 8207390 TI - Identification of the feline herpesvirus type 1 (FHV-1) genes encoding glycoproteins G, D, I and E: expression of FHV-1 glycoprotein D in vaccinia and raccoon poxviruses. AB - The genome of feline herpesvirus type 1 (FHV-1), the major cause of viral upper respiratory disease in cats, contains several genes encoding homologues of herpes simplex virus type 1 (HSV-1) glycoproteins. Restriction mapping studies have indicated that the group D genome of FHV-1 contains a unique short region that is 9.0 kb long. The nucleotide sequence of a 6.2 kb portion of this region was determined. Analyses of this sequence have identified five open reading frames capable of encoding homologues to HSV-1 protein kinase and glycoproteins gG, gD, gI and gE. Since gD of FHV-1 is most likely an immunologically important polypeptide, vaccinia and raccoon poxvirus recombinants expressing this glycoprotein were generated. In an indirect fluorescent antibody test these recombinants reacted strongly with a rabbit anti-FHV-1 serum. High titres of virus-neutralizing antibodies were also generated in rabbits inoculated with the vaccinia virus recombinant. A 53K viral polypeptide (gD) was detected with this antiserum on Western blots containing polypeptides from potassium tartrate purified virions. PMID- 8207391 TI - An analysis of the in vitro and in vivo phenotypes of mutants of herpes simplex virus type 1 lacking glycoproteins gG, gE, gI or the putative gJ. AB - Mutants of herpes simplex virus type 1 (HSV-1) lacking glycoproteins gG, gE, gI or the putative gJ were constructed by inserting a lacZ expression cassette within the US4, US8, US7 and US5 genes respectively. Revertant viruses were then constructed by rescue with a wild-type DNA fragment. Each of these mutant viruses, by comparison with the parental virus HSV-1 SC16, exhibited normal particle to infectivity ratios, and had no discernible phenotypic abnormalities in baby hamster kidney-21 cells following high or low multiplicity infections. Infection of mice by scarification of the ear with these mutant viruses showed the following. (i) Interruption of the US5 (gJ) gene has no effect on the ability of HSV-1 to multiply at the inoculation site or its ability to enter or multiply in the peripheral or central nervous system (CNS). This shows that the US5 gene provides a convenient site for the insertion of foreign genes for both in vitro and in vivo studies. (ii) Disruption of the US4 (gG) gene results in marginal attenuation in the mouse ear model. (iii) Disruption of the US7 (gI) or US8 (gE) genes results in pronounced attenuation; virus was rapidly cleared from the inoculation site and was barely detectable in sensory ganglia or in the CNS. The failure of gI-negative or gE-negative viruses to replicate efficiently at the inoculation site in vivo led to the investigation of virus behaviour in epithelial cells in vitro. Viruses lacking gE or gI adsorbed to and entered these cells at normal rates compared with the parental virus, but formed minute plaques. This is consistent with a failure of cell-to-cell spread by the cell contact route. This was confirmed by measurement of the rate of increase in infectious centre numbers following low multiplicity infections. The view that gE and gI influence interactions between cells at the plasma membrane was reinforced by showing that the introduction of disrupted gE or gI genes into a syncytial, but otherwise syngeneic, background resulted in a non-syncytial phenotype. We conclude that the gE-gI complex plays a part, at least in some cell types, in the interactions at the cell surface that allow transmission of the virus from infected to uninfected cells by cell contact. In syncytial strains this leads to uncontrolled membrane fusion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8207392 TI - The analysis of polypeptides in the nuclei and cytoplasm of cells infected with murine herpesvirus 72. AB - Twenty-six polypeptides in murine herpesvirus isolate 72 (MHV-72) were identified and the synthesis and accumulation of 21 virus-specific polypeptides in Vero cells during the course of productive infection with MHV-72 were examined. Five of the infected cell polypeptides accumulated within the nuclei and nine accumulated within the cytoplasm of MHV-72-infected cells. Seven polypeptides were identified within the nuclei and cytoplasm in equivalent amounts. The major capsid protein was shown to have an M(r) of 161K. Thirteen virus-specific polypeptides were solubilized with Nonidet P-40 or radioimmunoprecipitation assay buffer and immunoprecipitated with rabbit and mouse immune sera. Analysis of the polypeptides of MHV-72 indicate a closer resemblance between MHV-72 and the gammaherpesviruses herpesvirus saimiri and Epstein-Barr virus than with the alphaherpesvirus herpes simplex virus type 1. PMID- 8207393 TI - Expression and DNA binding of budgerigar fledgling disease virus large T antigen. AB - Budgerigar fledgling disease virus (BFDV) represents the first non-mammalian member of the polyomavirus genus and possesses uncommon structural and biological properties. Recombinant baculoviruses were constructed to express BFDV small t antigen, large T antigens, as well as a large T deletion mutant Td and beta galactosidase-Td fusion proteins to high levels in infected insect cells. A recombinant virus containing a genomic copy of the BFDV early region was used for small t antigen expression, and corresponding intron-deleted cDNAs for production of large T antigen derivatives. Recombinant T as well as authentic T antigen proteins from infected chicken embryo fibroblasts were purified using both immunoaffinity and DNA affinity column chromatography. We present evidence that the large T antigen interacts specifically with DNA sequences present in the non coding region of BFDV; by indirect DNA immunoprecipitation mapping and DNase I footprinting, four regions including 12 DNA-binding sites have been determined that cover most of the BFDV non-coding region. The T antigen binding pattern observed suggests a protein-DNA interaction system considerably different from those of simian virus 40 and other polyomaviruses. PMID- 8207394 TI - Biochemical and mutational analysis of the polyomavirus core promoter: involvement of nuclear factor-1 in early promoter function. AB - The polyomavirus enhancer is separated from the early RNA initiation sites by a 120 bp promoter region. To identify the core promoter elements, we introduced base-substitution mutations within the potential elements in the vicinity of the RNA initiation site. Three of these mutants, two with mutations within a putative nuclear factor-1 (NF-1) binding site and the other within the TATA box, exhibited reduced promoter activity by about threefold in the mouse NIH 3T3 cell line. The activity of the other three mutants was either little affected or remained unchanged. Mobility shift assays using specific competitors and antibodies against NF-1 demonstrated the binding of a protein of the NF-1 family at a site adjacent to the TATA box, suggesting a role for NF-1 binding in early promoter function. The effect of these mutations was also evaluated in undifferentiated mouse embryonal carcinoma (F9) cells in the presence of an additional mutation (F441) at nucleotide position 5233. This additional mutation creates a strong binding site for a transcription factor, TEF-1, and helps the virus to grow in this cell line. While the TATA box and the GC box mutants behaved qualitatively in a similar fashion, the NF-1 motif now played a minor role in F9 cells. Western blot experiments demonstrated low levels of NF-1 protein in this cell line. The NF-1 motif partially overlaps a T-antigen binding motif and this motif is not involved in T-antigen-mediated regulation of the early promoter. Our results suggest that a protein of the NF-1 family binds to the core promoter and is important for early transcription in vivo. We further demonstrate that undifferentiated F9 cells contain a very low level of NF-1 and the F441 mutant possibly follows a different mechanism for promoter function in these cells. PMID- 8207395 TI - Proposals for a new classification of iridescent viruses. AB - The need for comparative studies of iridoviruses to elucidate the relationships between them has been well appreciated. Sixteen iridoviruses, including type species from each of the four recognized genera of the Iridoviridae, were compared by restriction endonuclease characterization, hybridization to the major structural protein (MSP) gene of an invertebrate iridescent virus (IV) isolate at various stringencies, PCR amplification of the MSP gene region and by dot-blot hybridization studies. The results broadly supported previous serological studies. The vertebrate iridoviruses, frog virus 3 (genus Ranavirus) and flounder lymphocystivirus (genus Lymphocystivirus), appeared distinct from one another and from the invertebrate isolates. Naming and numbering invertebrate IV isolates according to history and host is no longer useful since IVs infect a number of species. A revised system, involving names based on the geographical origin of the isolate is proposed, in line with other virus families. The large IVs of invertebrates represented by Vero Beach IV (previously IV3 or mosquito IV; genus Chloriridovirus) showed little similarity to any other IVs. Members of the genus Iridovirus, the small invertebrate IVs, fell into three distinct groups of interrelated isolates. The largest group, containing the Plowden (IV1), Tia (IV2), Nelson (IV9, IV10 and IV18), Aberystwyth (IV22), Srinagar (IV24), Fort Collins (IV29) and Stoneville (IV30) iridoviruses, is named the Polyiridovirus complex. The Plowden iridovirus (IV1) is suggested as type species for this complex given the data available on its molecular biology. Based on previously published data, Timaru (IV16 and IV19) and Uitenhage (IV23) iridoviruses are also assigned to this complex. The second but smaller group is named the Oligoiridovirus complex, which includes Dazaifu (IV6) as the type species and contains Ntondwe (IV21 and IV28) on a tentative basis. Riverside IV (IV31) was distinct from both of the other groups, and is proposed as a third complex, Crustaceoiridovirus. PMID- 8207396 TI - Evidence for recent genetic variation in monkeypox viruses. AB - DNA from isolates of monkeypox virus, when digested with the endonuclease PstI, gave fragment-size profiles which correlated with the geographic area from which the isolate originated. Although some of the differences were located subterminally in the genome, others mapped to the central conserved region. Further differentiation of the viral genomes was sought by analysis of a short region within the central conserved part of the genome that appeared to be a partially deleted counterpart of an intact 1024 bp open reading frame (ORF) present in variola and vaccinia virus genomes. We reasoned that this region would not be conserved by functional selection and would therefore be likely to show more variation between isolates of monkeypox virus. The deletions found in monkeypox virus isolates from Liberia and from Benin were almost the same as that which we had previously found in the Denmark strain. A much shortened ORF, potentially coding for a product of 133 amino acids, was retained in all three West African isolates, but three Zairean isolates each showed an identical series of small insertions and deletions which effectively abolish the ORF. Three deletions, present in all isolates, must pre-date the geographical separation of monkeypox virus lineages; other, presumably more recent, changes differ between the Zairean and West African isolates. In contrast, the base similarity was found to be more than 99% when all the monkeypox virus sequences were appropriately aligned. This, in a disrupted and presumably nonfunctional gene also indicates that the changes described are recent. It is suggested that insertions and deletions occur regularly during poxvirus DNA replication, but are preserved only in sequences that are not required for continued transmission in the natural host. PMID- 8207397 TI - Molecular cloning, physical mapping and cross-hybridization of the murine adenovirus type 1 and type 2 genomes. AB - Murine adenovirus (MAd) type 1 strain FL and type 2 strain K87 genomes were cloned into plasmid pAT153 as HindIII restriction fragments. The MAd-1 and MAd-2 DNA genomes, 30.10 kb and 34.71 kb in length respectively, were mapped using BglII, ClaI, EcoRI, HindIII and SphI restriction endonuclease cleavage sites. In view of the large differences found between the MAd-1 and MAd-2 genomes in terms of the number and location of restriction sites, cross-hybridization experiments were performed. Homologous DNA sequences were located on the MAd-1 and MAd-2 physical maps. Both viruses are also genetically related to human adenovirus type 2 (HAd-2). Nucleotide sequences shared by HAd-2 and the MAds code for structural proteins, which may explain the antigenic similarities between these viruses from different origins. Our results confirm the existence of two distinct adenovirus species in the mouse. PMID- 8207398 TI - Mapping of determinants of the host range for canine cells in the genome of canine parvovirus using canine parvovirus/mink enteritis virus chimeric viruses. AB - Feline panleukopenia virus (FPLV), mink enteritis virus (MEV) and canine parvovirus (CPV) are more than 98% similar in DNA and predicted amino acid sequences, but they show different host-cell specificities; CPV is able to replicate in canine cells in culture, whereas FPLV and MEV cannot or replicate only to a low titre. To map the genomic region responsible for the host range of CPV in vitro, CPV/MEV chimeric viruses were generated by transfecting infectious CPV/MEV chimeric plasmids into a cultured feline kidney cell line, and their host cell ranges were analysed. The 60 to 91 map units (m.u.) region of the CPV genome, which contains a part of the capsid protein (VP) gene encoding from amino acid 91 (in the VP2 sequence) to the carboxy terminus of VP protein, was required to impart the ability to replicate in canine cells to MEV, although the chimeric virus containing the 60 to 91 m.u. region of the CPV genome in the MEV background did not replicate in canine cells as efficiently as did CPV derived from the infectious plasmid of CPV. Not only the VP gene, but also a part of the NS gene of CPV were considered to participate in the full expression of the ability to replicate in canine cells. Within the 60 to 91 m.u. region, five of nine amino acid changes between MEV-Abashiri and CPV-Y1 were thought to be phylogenetically CPV-common; however, a recombinant virus containing all five amino acid changes of CPV in the MEV background replicated minimally in canine cells. PMID- 8207399 TI - Recombinant protein fragments from haemorrhagic septicaemia rhabdovirus stimulate trout leukocyte anamnestic responses in vitro. AB - This work shows that viral protein fragments are capable of stimulating fish anamnestic immunological responses in leukocytes from the rainbow trout (Oncorhynchus mykiss, W.). Recombinant protein fragments of glycoprotein and nucleoprotein from the rhabdovirus causing viral haemorrhagic septicaemia of trout (VHSV), were cloned and expressed in Escherichia coli, Yersinia ruckeri (a trout pathogen) and Saccharomyces cerevisiae. The recombinant protein fragments stimulated anamnestic responses in leukocyte cultures derived from the anterior kidney of survivors of VHSV infection but not from uninfected trout. Two types of stimulatory anamnestic responses were detected, (i) a stimulation of lymphoproliferation as measured by thymidine incorporation assays and (ii) an increase in number, spreading and size of cells as determined by fibrin-clot and/or flow cytometry techniques. The evidence presented suggests that both adherent and non-adherent trout cell populations are needed for the immunological response to VHSV in this primitive vertebrate. The possible use of in vitro lymphoproliferation assays as a preliminary screening method for candidate fish vaccines prior to their testing in vivo is discussed. PMID- 8207401 TI - Linear antigenic and immunogenic regions of the respiratory syncytial virus P protein. AB - Three linear antigenic regions on the P protein from human respiratory syncytial virus (RSV) subgroup A (strain A2) were represented by peptides that reacted with monoclonal antibodies and with sera from humans with recent or previous RSV infection. The determinants were localized within three hydrophilic regions of the P protein: Pro91 to Asp110, Ser161 to Lys180 and Glu221 to Phe241. The role of individual amino acids in the epitopes defined by monoclonal antibodies was determined. Two monoclonal antibodies reacting with the same antigenic site were found to detect epitopes that had different amino acid dependencies. Rabbit hyperimmune sera raised against selected peptides specifically precipitated different forms of the P protein from RSV-infected 35S-labelled cell extracts in a radioimmune precipitation assay. These findings have implications for forthcoming structural-functional studies of RSV capsid component interactions and also for serological diagnosis of RSV infection. PMID- 8207400 TI - Protective efficacy in mice of post-exposure vaccination with vaccinia virus recombinant expressing either rabies virus glycoprotein or nucleoprotein. AB - Mice vaccinated intraperitoneally (i.p.) with 10(7) p.f.u. of a vaccinia virus recombinant expressing either the glycoprotein (rVac-G) or nucleoprotein (rVac-N) of rabies virus 3 weeks before challenge were protected against peripheral lethal infection. Similarly, by post-exposure vaccination in which mice were first infected with rabies virus and subsequently vaccinated i.p. with the recombinant, rVac-G conferred protection when given immediately following infection and up to 24 h after infection. Prior treatment of those mice with anti-CD8 monoclonal antibodies (MAb) did not significantly affect the outcome of the infection. In contrast, rVac-N failed to confer protection even with higher doses (10(8) p.f.u.) of the virus or even when administered by the intradermal route. Anti nucleoprotein antibody production by these mice was not suppressed by prior rabies virus infection and the levels and the time of antibody production were similar to those of anti-glycoprotein antibody production in mice vaccinated with rVac-G after rabies virus infection. The cytotoxic T lymphocyte response was also not down-regulated by rabies virus in the mice that were given rVac-N. Possible mechanism(s) for the ineffectiveness of rVac-N by post-exposure vaccination in contrast to pre-exposure vaccination was discussed. PMID- 8207403 TI - Deletion of a single N-linked glycosylation site from the transmembrane envelope protein of human immunodeficiency virus type 1 stops cleavage and transport of gp160 preventing env-mediated fusion. AB - The transmembrane envelope glycoprotein (gp41) of human immunodeficiency virus type 1 possesses four consensus sites (Asn-X-Ser/Thr) for the incorporation of N linked sugars situated on the extracellular domain of the molecule. The purpose of this investigation was to determine the significance of each of these sites in relation to the structure and function of the viral envelope glycoprotein. Each of the four sites was removed by in vitro mutagenesis of gp160 sequence in the non-infectious viral clone pEVd1443, so that amino acids 616, 621, 642 and 679 were each changed from asparagine to serine. The effects of mutagenesis were assessed by syncytium assay after wild-type or mutant envelope clones had been transfected into CD4+ HeLa cells. Removal of the glycosylation site at position 642 resulted in the synthesis of precursor gp160 that was neither cleaved, to give gp120 and gp41, nor transported to the plasma membrane of transfected cells. A consequence of these events was that envelope mutant 642 failed to induce syncytia between neighbouring cells in which it had been expressed. The results of this study indicate that N-linked glycosylation of Asn-642 in the glycoprotein produced by the pEVd1443 expression system is necessary for the correct intracellular processing of gp160 to yield surface-expressed, fusogenic gp41. PMID- 8207402 TI - Fluctuation of hepatitis C virus quasispecies in persistent infection and interferon treatment revealed by single-strand conformation polymorphism analysis. AB - Hepatitis C virus (HCV) populations in vivo consist of heterogeneous mixtures of genetically different but closely related variants defined as a 'quasispecies'. The longitudinal fluctuation of HCV quasispecies populations in chronic hepatitis C has not been elucidated. Serial plasma samples were obtained from four patients with chronic hepatitis C (two patients without any treatment and two patients treated with interferon), and cDNA fragments containing the 5'-terminal region of the E2 gene of HCV were amplified from plasma RNA using PCR. Since conventional cloning of PCR products detects only a small part of the entire population, PCR products of each sample were separated by electrophoresis using single-strand conformation polymorphism (SSCP) analysis, which can distinguish DNA fragments of the same size as different electrophoretic bands depending on their sequence specific conformation. Separated DNA fragments were recovered from SSCP bands in gels and their nucleotide sequences determined. SSCP electrophoresis separated PCR products into bands with different mobility. Sequence analysis of these bands confirmed that HCV populations in each patient are composed of quasispecies with different E2-hypervariable regions (HVR), which are known to contain antibody epitopes. Different patterns of variation in the HVR of quasispecies were observed in individual patients with different clinical features over time during chronic infection. Following interferon treatment, some quasispecies disappeared during the treatment and reappeared after the end of the treatment, whereas other quasispecies in the same patient remained during the treatment suggesting that the sensitivity to interferon is different among quasispecies. PMID- 8207404 TI - Mutations in the helper component protease gene of zucchini yellow mosaic virus affect its ability to mediate aphid transmissibility. AB - The nucleotide sequence of the helper component protease (HC-Pro) genes of three zucchini yellow mosaic virus (ZYMV) strains has been compared with that of a helper-deficient strain of ZYMV-HC. The comparisons revealed three unique deduced amino acid differences. Two of these mutations were located in regions which are conserved in other potyviruses. The role of these mutations in aphid transmissibility was examined by exchanging DNA fragments of part of the deficient HC-Pro gene with the respective section within the gene of the infectious full-length clone of the aphid-transmissible ZYMV. The first exchange included two of the three mutations, the first coding for a change from Asp to Gly (in a non-conserved region) and the second coding for a change from Arg to Ile [within the Phe-Arg-Asp-Lys (FRNK) conserved box]. This exchange resulted in a reduced transmission (20.6% for the mutated virus compared with 57.4% in the normal ZYMV when acquired from plants and 37.2% compared with 83.1%, respectively, when acquired from membranes). The second exchange incorporated a single mutation [conferring a change from Thr to Ala within the Pro-Thr-Lys (PTK) conserved box]. This single mutation resulted in almost total loss of HC activity in aphid transmission both from plants and from membranes. The Lys residue in the conserved Lys-Ile-Thr-Cys (KITC) box, which is related to loss of HC activity in potato virus Y, tobacco vein mottling virus and in the Michigan strain of ZYMV, is unchanged in the helper-deficient ZYMV. It is therefore proposed that more than one site in HC-Pro may be functionally related to aphid transmissibility. The possible reasons for the role of these mutations in helper activity in aphid transmission of ZYMV are discussed. PMID- 8207405 TI - Screening of the closterovirus genome by degenerate primer-mediated polymerase chain reaction. AB - The genome of beet yellows virus (BYV), the type representative of the closterovirus group, encodes a homologue of the cellular heat-shock protein (HSP) 70 family. A pair of degenerate primers targeted to motifs A and E, which are highly conserved in HSP70s, was synthesized. Genomes of several definite and possible members of the closterovirus group were screened for the presence of the HSP70 gene with PCR using these degenerate primers. BYV, citrus tristeza virus (CTV), beet yellow stunt virus (BYSV) and carnation necrotic fleck virus templates produced 1 kb amplification products, which were shown by sequencing to represent fragments of the respective HSP70 genes. Further screening was performed with an additional degenerate primer targeted to the motif IV of the putative viral polymerase. This degenerate primer and specific primers complementary to the 5' region of the HSP70 genes of the respective viruses were used to estimate the distance between polymerase motif IV and the start point of the HSP70 gene for BYV (approximately 1.1 kb), CTV and BYSV (around 2.0 kb) by PCR. The amplified genome regions of CTV (3026 nucleotides) and BYSV (2837 nucleotides) were cloned and sequenced. CTV and BYSV were found to encode the gene for an additional 30K (BYSV) or 33K (CTV) protein between the polymerase and the small hydrophobic protein genes, which was absent in BYV. These two 30K proteins displayed very weak similarity to each other, unlike the highly conserved polymerases, hydrophobic proteins and HSP70s of BYV, CTV and BYSV. Degenerate primer-mediated PCR proved to be an efficient tool for rapid screening and subsequent cloning of the viral genomes. PMID- 8207406 TI - Heterologous encapsidation of recombinant pea early browning virus. AB - The coat protein gene of pea early browning virus (PEBV) was replaced with that of another tobravirus, tobacco rattle virus (TRV strain PPK20). The recombinant virus multiplied efficiently in the systemic host Nicotiana benthamiana and, on the local lesion host Phaseolus vulgaris, produced symptoms typical of PEBV rather than TRV showing that viral coat protein is not a determinant for lesion morphology. Both viral RNAs were encapsidated by TRV coat protein although the shorter particles (encapsidated RNA-2) did not form a discrete population. Evidence is presented to suggest involvement of nucleotide sequences upstream of the coat protein gene in virus particle assembly. PMID- 8207407 TI - Nucleotide sequence of apple mosaic ilarvirus RNA 4. AB - The complete nucleotide sequence of apple mosaic ilavirus RNA 4 was obtained from cloned cDNAs and direct sequencing of the 5'-terminal RNA region. The sequence is 891 nucleotides long and can encode a protein of 226 amino acids (M(r) 25,171) that, by analogy to alfalfa mosaic virus (AlMV) and tobacco streak virus (TSV), should correspond to the coat protein (CP). Database comparisons showed that no significant similarity to other proteins was apparent. Analysis of the CP sequence revealed a putative 'zinc finger' domain and a region rich in basic residues at the amino-terminal portion of the protein, similar to that of TSV. The secondary structure proposed for the 3'-terminal region of RNA 4 shows the presence of three hairpin structures flanked by the tetranucleotide AUGC that are highly similar to those previously described in the RNA 4 species from AlMV and TSV. These results support the idea that both features (metal-binding domain and highly conserved hairpin structures) are characteristics of ilarviruses and are probably involved in the peculiar 'genome activation' phenomenon described in these viruses. PMID- 8207408 TI - Nucleotide sequence of the original Brazilian isolate of coleus yellow viroid from Solenostemon scutellarioides and infectivity of its complementary DNA. AB - The complete nucleotide (nt) sequence of the original coleus yellow viroid (CYVd) from Solenostemon scutellarioides, 'Golden Bedder', has been determined. The covalently closed single-stranded CYVd RNA molecule consists of 248 nt residues which assumes a rod-like secondary structure when folded in the model of lowest free energy. The sequence was determined by direct sequencing of RNA and from three overlapping cDNA clones. Comparison of the CYVd sequence with that of Coleus blumei viroid 1 (CbVd 1) from Germany demonstrated that they are closely related. The differences observed in the genome organization of CYVd relative to CbVd 1 were at three sites: position 25 (one U deletion), position 26 (a U was replaced by an A) and position 241 (one A insertion). The first two mutations were detected in one A-rich segment of eight nt (between positions 25 and 34). Northern blot hybridization of partially purified nucleic acids from the leaf tissue of S. scutellarioides 'Frilled Fantasy', inoculated with double-stranded cDNA, demonstrated that this fragment was infectious. These data enable CYVd to be assigned to the viroid class of plant pathogens, based on its biological properties and molecular structure. This work also gives additional support to the present classification system, in which the viroids isolated from S. scutellarioides form a distinct subgroup. PMID- 8207409 TI - Antibody-dependent cellular cytotoxicity and neutralization of human immunodeficiency virus type 1 by high affinity cross-linking of gp41 to human macrophage Fc IgG receptor using bispecific antibody. AB - Human monocytes/macrophages, which express Fc receptors for IgG are involved in human immunodeficiency virus type 1 (HIV-1) infection and pathogenesis. These receptors are known to mediate numerous immunological functions including cell mediated killing and possibly targeting of HIV to the lysophagosome monocyte derived macrophage (MDM) entry route for virus neutralization. To study both activities in HIV-1 infection, MDM Fc gamma RI was specifically selected using bispecific antibody (Bs-Ab) containing whole human monoclonal antibody against gp41 and the Fab' fragment of murine anti-Fc gamma RI 22.2 antibody. Bs-Ab was found to mediate potent antibody-dependent cellular cytotoxicity and virus neutralization. PMID- 8207410 TI - Single- and multi-hit kinetics of immunoglobulin G neutralization of human immunodeficiency virus type 1 by monoclonal antibodies. AB - A quantal assay, based on syncytium formation in the human T cell leukaemia derived C8166 cell line, was used to determine the kinetics of human immuno deficiency virus type 1 (HIV-1) strain IIIB neutralization. Three rat monoclonal antibodies (MAbs) were used, under physiological conditions of temperature and antibody concentration. MAb ICR39.3b (IgG2b) neutralized virus with no lag period while the other two MAbs, ICR39.13g (IgG2b) and ICR41.1i (IgG2a), neutralized with lag periods of 5 min and 15 min respectively. It was calculated that the latter two MAbs mediated neutralization by about two and three molecules of IgG per virion respectively. The highest neutralization rate constant (for MAb ICR 41.1i) was over 300-fold less than that of MAbs specific for the haemagglutinin of the enveloped influenza virus type A and for poliovirus type 1. PMID- 8207411 TI - Basal and Tat-transactivated expression from the human immunodeficiency virus type 1 long terminal repeat in human placental trophoblast rules out promoter enhancer activation as the partial block to viral replication. AB - We have analysed the capacity of the trophoblast-derived malignant cell lines BeWo, JAR and JEG-3, and primary cultures of highly purified trophoblast cells to support the basal and Tat-mediated trans-activation-enhanced transcriptional activity of two distinct human immunodeficiency virus type 1 (HIV-1) isolates. Kinetic studies based on expression of long terminal repeat (LTR)-chloramphenicol acetyltransferase (CAT) constructs revealed that LTRs of both the prototype strain 3B and the highly cytopathic Zairean variant NDK were activated significantly in all target cells. Overall, the strongest activation was observed in primary trophoblasts. A novel modification of quantitative PCR was used to normalize LTR expression for transfection efficiency, enabling the calculation of specific expression rates in terms of muU CAT enzyme per fmol of transfected DNA. Using the latter criterion we determined that LTRs of both viruses were activated in decreasing order from trophoblasts to JAR, JEG-3 and BeWo cells; furthermore, the expression of HIV-1 3B LTR always significantly surpassed that of HIV-1 NDK. The effects of trans-activation on either of the LTRs, when assayed in cotransfection assays with various amounts of HIV-1 NDK-Tat expression vector, increased in a dose-dependent fashion and were comparable in a particular neoplastic cell line. Furthermore, the cell-specific LTR activity patterns did not correspond to the abundance of transcription factors binding specifically to the viral NF kappa B and SP1 motifs. Unlike SP1-binding proteins which were relatively abundant, substantially smaller amounts of proteins with NF kappa B specificity were found in all cells. Despite this apparent deficit in NF kappa B activity, trophoblasts supported a high basal activity of both LTRs. These data indicate that an insufficiency of basal or Tat-trans-activated LTR activity cannot account for the low level of HIV-1 replication in this important cell type. PMID- 8207412 TI - Inhibition of infectious human immunodeficiency virus type 1 particle formation by Gag protein-derived peptides. AB - Sequential overlapping Gag protein-derived oligopeptides of human immunodeficiency virus type 1 (HIV-1) 22 to 24 amino acids long, were synthesized and tested in vitro for antiviral activity. Two synthetic peptides, one derived from the matrix protein p17 (NPGLLETSEGCRQ, amino acids 47 to 59) and one located in the capsid protein p24 (PAATLEEMMTA, amino acids 339 to 349) inhibited the production of infectious virus when added to HIV-1-infected cultures when used in the range of 20 to 200 micrograms/ml. As shown by thin section electron microscopy, peptide treatment resulted in the release of immature, deformed virus particles suggesting that the two peptides interfered with assembly and maturation. Other Gag protein-derived oligopeptides had little or no influence on virus production. To characterize further the functionally active regions we synthesized peptide derivatives with three consecutive amino acids substituted by alanine; they did not cause inhibition. Therefore the regions responsible for inhibition were located between amino acids 50 to 61 in p17, and 342 to 350 in p24. These observations might lead to the development of a new antiviral strategy affecting the late stage of virus replication. PMID- 8207413 TI - Differential transcription, without replication, of non-structural and structural genes of human parvovirus B19 in the UT7/EPO cell as demonstrated by in situ hybridization. AB - Erythroid progenitor cells are the main target for B19 parvovirus infection. The UT7 cell line demonstrates a marked erythroid differentiation on induction by erythropoietin (EPO) (UT7/EPO cells) and therefore appears to be a potential target for B19 parvovirus. We aimed to evaluate the presence and localization of B19 nucleic acids in UT7/EPO cells by in situ hybridization. Three digoxigenin labelled probes were used: two recognized specifically the non-structural region of the B19 genome and one probe was structural region-specific. In our experiment UT7/EPO cells were not permissive to B19 infection. Transcription led to nonstructural and structural gene transcripts without DNA replication or capsid protein synthesis. PMID- 8207414 TI - Characterization of the vaccinia virus L1R myristylprotein as a component of the intracellular virion envelope. AB - In many cases, virus-encoded acylproteins appear to localize to specific cellular and viral membranes and to be directly involved with the processes of virus morphogenesis and/or egress from the infected cell. It was therefore of interest to determine whether the major vaccinia virus (VV) myristylprotein, L1R, is specifically associated with one or more of the membranes enveloping various infectious forms of VV virions. To this end, single-membraned intracellular virions (INV) and extracellular enveloped virions (EEV), which are surrounded by at least two distinct membranes, were purified from VV-infected cell lysates. The location of the VV L1R protein was determined by using a monospecific anti-L1R serum to detect the L1R protein by immunoblot in INV- and EEV-containing fractions, by examining the proteinase K sensitivity of the L1R protein in intact INV and EEV particles, and by immunoelectron microscopy. The data obtained clearly indicate that although the L1R protein is a constituent of both the INV and EEV particles, it is exclusively found in the inner INV-specific membrane. These results are discussed with regard to the potential role of the VV L1R protein in the primary intracellular envelopment of infectious VV particles. PMID- 8207415 TI - Comparison of M and N gene sequences distinguishes variation amongst equine arteritis virus isolates. AB - cDNA copies of the M and N genes of equine arteritis virus (EAV) isolates were synthesized by reverse transcription followed by polymerase chain reaction amplification. The cDNA was subjected to a cycle sequencing strategy using Taq polymerase, and the nucleotide and derived amino acid sequences of 10 virus isolates were compared. The M and N genes of all isolates had the same initiation and termination sites as the prototype Bucyrus strain and the encoded proteins were conserved between viruses. Comparison of nucleotide sequence homologies and phylogenetic tree analysis implied the existence of three EAV variants originating from the U.S.A. (Bucyrus), Austria (Vienna) and Switzerland (Bibuna), and suggested that RNA recombination between EAV isolates may have occurred. PMID- 8207416 TI - Multiple repeating motifs are found in the 3'-terminal non-translated region of Semliki Forest virus A7 variant genome. AB - We have analysed the cDNA coding for the envelope glycoprotein (E1) gene and the terminal non-translated regions (NTRs) of the avirulent Semliki Forest virus (SFV) A774 (A7) variant. The E1 gene exhibited 98.5% identify to the SFV prototype strain L10 (WT) sequence at the nucleotide level. Of the 34 single base substitutions, six led to a change in the deduced amino acid sequence. The 3' NTR of A7 consisted of a 101 nucleotide sequence, not found in WT, followed by five tandemly arranged sequence motifs, two of which were truncated forms of the others. One full-length and one truncated repeat are found at the 3' NTR of WT. The repeats of A7 were followed by a non-repeating sequence, very similar to the equivalent region in WT. Owing to the unique sequence motif and the tandem repeats, the 3' NTR of A7 is 334 nucleotides longer than that of WT. Each of the repeats had an internal 12 nucleotide motif complementary to a conserved sequence in the 5'-terminal non-structural protein 1-encoding region, thought to be important in alphavirus RNA replication. In the 5' NTR, three point mutations were found. The conserved sequence binding to the repeated 3' motifs was identical in A7 and WT. PMID- 8207417 TI - Comparison of nucleotide and deduced amino acid sequence of the 5' non-coding region and structural protein genes of the wild-type Japanese encephalitis virus strain SA14 and its attenuated vaccine derivatives. AB - Nucleotide sequences of the 5' non-coding region and the structural protein genes of the live, attenuated Japanese encephalitis vaccine virus strains SA14-2-8 and SA14-5-3 and the wild-type parental strain SA14/USA were determined. SA14-2-8 differed from SA14/USA by 13 nucleotides and eight amino acids whereas SA14-5-3 differed from SA14/USA by 15 nucleotides and eight amino acids. A comparison of the 5' non-coding region and amino acid sequences of the structural proteins of these two attenuated vaccine strains and of vaccine strains SA14-14-2/PHK and SA14-14-2/PDK with three sequences of their wild-type parent SA14 virus was performed. This revealed only two common amino acid substitutions at positions 138 and 176 in the envelope (E) protein. The substitution at E138 was predicted to cause a change in the secondary structure of the E protein. These two amino acid substitutions in the E protein may contribute to attenuation of the Japanese encephalitis vaccine viruses. PMID- 8207418 TI - SCID mouse spleen does not support scrapie agent replication. AB - BALB/c and severe combined immunodeficiency (SCID) mice were inoculated intracerebrally or intraperitoneally with scrapie agent strain ME7 to examine the role of functional lymphocytes and follicular dendritic cells in splenic infectivity and PrPSc accumulation. Intracerebrally inoculated BALB/c and SCID mice developed the clinical signs and microscopic lesions characteristic of scrapie. Spleens from terminally affected BALB/c mice contained PrPSc which was detectable by immunoblot analysis; SCID mouse spleens did not contain detectable PrPSc. SCID mouse spleens collected during the first 90 days after intraperitoneal infection contained neither infectivity nor PrPSc. PMID- 8207419 TI - Glia of the cholinergic electromotor nucleus of Torpedo are the source of the cDNA encoding a GAT-1-like GABA transporter. AB - A PCR-based strategy was used to clone DNAs encoding Na(+)- and Cl(-)-dependent cotransport proteins using DNA from the cholinergic electromotor nucleus of Torpedo californica. This cloning strategy resulted in the isolation of a cDNA clone that shows strong nucleotide sequence homology to the GABA transporter-1 (GAT-1) types of rat and human brain. When expressed in frog oocytes, this transporter mediates the uptake of GABA. Moreover, physiologically and pharmacologically, the Torpedo protein behaves very similarly to the rat and human GAT-1 proteins. However, in contrast to the predominantly neuronal localization of the mammalian GAT-1 proteins, the mRNA for the fish protein is found almost exclusively in glial elements of the electromotor nucleus. This unexpected discovery of a GABA transporter cDNA in a nucleus that has no previously characterized GABAergic innervation raises questions about the role of GABA and this transporter in the electromotor system. Several speculative models for GABA function are proposed. PMID- 8207420 TI - L-3,4-dihydroxyphenylalanine-induced dopamine release in the striatum of intact and 6-hydroxydopamine-treated rats: differential effects of monoamine oxidase A and B inhibitors. AB - Administration of L-DOPA (50 mg/kg) elicits a significant increase in extracellular dopamine in striata of rats treated with the catecholaminergic neurotoxin 6-hydroxydopamine but not in striata of intact rats. To assess the role of dopaminergic nerve terminals in determining the effects of exogenous L DOPA on extracellular dopamine levels in striatum, we examined the relative contributions of monoamine oxidase A and monoamine oxidase B to the catabolism of dopamine synthesized from exogenous L-DOPA. Extracellular concentrations of dopamine and its catabolite, 3,4-dihydroxyphenylacetic acid, were monitored with in vivo dialysis in striata of intact rats and of rats with unilateral 6 hydroxydopamine lesions of striatal dopamine. Clorgyline (2 mg/kg), an inhibitor of monoamine oxidase A, significantly increased dopamine and decreased 3,4 dihydroxyphenylacetic acid in intact but not in dopamine-depleted striata. Inhibition of monoamine oxidase B with either L-deprenyl (1 mg/kg) or Ro 19-6327 (1 mg/kg) did not significantly affect dopamine or 3,4-dihydroxyphenylacetic acid in striata of intact or dopamine-depleted rats. In intact rats, administration of clorgyline in conjunction with L-DOPA produced a > 20-fold increase in dopamine and prevented the L-DOPA-induced increase in 3,4-dihydroxyphenylacetic acid. Although both L-deprenyl and Ro 19-6327 administered in combination with L-DOPA elicited a small but significant increase in dopamine, levels of 3,4 dihydroxyphenylacetic acid were not affected. In rats pretreated with 6 hydroxydopamine, clorgyline had no significant effect on the increases in dopamine and 3,4-dihydroxyphenylacetic acid elicited by L-DOPA. Furthermore, neither L-deprenyl nor Ro 19-6327 affected L-DOPA-induced increases in dopamine and 3,4-dihydroxyphenylacetic acid in dopamine-depleted striata. The present findings indicate that deamination by monoamine oxidase A is the primary mechanism for catabolism of striatal dopamine, both under basal conditions and after administration of exogenous L-DOPA. Loss of dopaminergic terminals eliminates this action of monoamine oxidase A but does not enhance deamination by monoamine oxidase B. These data support a model in which exogenous L-DOPA elicits enhanced extracellular accumulation of dopamine in the dopamine-depleted striatum because some transmitter synthesis occurs at nondopaminergic sites and the dopamine terminals that normally take up and catabolize this pool of transmitter are absent. PMID- 8207421 TI - Different modulation of protein kinase C isozymes in dibutyryl cyclic AMP differentiated PC12h cells. AB - PC12h cells can be differentiated into sympathetic neuron-like cells by various agents, including nerve growth factor, basic fibroblast growth factor, cyclic AMP analogues, and protein kinase C (PKC) activators. To study the involvement of PKC in the process of PC12h cell differentiation by cyclic AMP treatment, PKC isozymes (alpha, beta I, beta II, and gamma) were analyzed using column chromatography and immunoblotting. Two PKC isozymes, PKC(alpha) and PKC(beta II), were predominantly detected in PC12h cells. When stimulated by dibutyryl cyclic AMP, PKC(alpha) levels declined in the cytosolic fraction of the cells, whereas PKC(beta II) levels increased. Increased PKC(beta II) levels were also detected in the particulate fraction, whereas particulate PKC(alpha) levels did not change. The total PKC activity decreased in the cytosolic fraction following cyclic AMP stimulation of PC12h cells, whereas it stayed constant in the particulate fraction. Fractionation on a hydroxyapatite column showed a decreased level of PKC(alpha) activity and a transient increase followed by a decreased level of PKC(beta II) activity. This discrepancy between increased PKC(beta II) immunoreactivity and reduced PKC(beta II) activity suggested the presence of nonactivatable PKC(beta II) in cyclic AMP-treated PC12h extract. These findings indicate that PKC(alpha) and PKC(beta II) are differentially regulated during the differentiation of PC12h cells. In addition, the differentiation of PC12h cells triggered by cyclic AMP seems to involve characteristic alterations of PKC isozymes. PMID- 8207422 TI - Kinesin mRNA is present in the squid giant axon. AB - Recently, we reported the construction of a cDNA library encoding a heterogeneous population of polyadenylated mRNAs present in the squid giant axon. The nucleic acid sequencing of several randomly selected clones led to the identification of cDNAs encoding beta-actin and beta-tubulin, two relatively abundant axonal mRNA species. To continue characterization of this unique mRNA population, the axonal cDNA library was screened with a cDNA probe encoding the carboxy terminus of the squid kinesin heavy chain. The sequencing of several positive clones unambiguously identified axonal kinesin cDNA clones. The axonal localization of kinesin mRNA was subsequently verified by in situ hybridization histochemistry. In addition, the presence of kinesin RNA sequences in the axoplasmic polyribosome fraction was demonstrated using PCR methodology. In contrast to these findings, mRNA encoding the squid sodium channel was not detected in axoplasmic RNA, although these sequences were relatively abundant in the giant fiber lobe. Taken together, these findings demonstrate that kinesin mRNA is a component of a select group of mRNAs present in the squid giant axon, and suggest that kinesin may be synthesized locally in this model invertebrate motor neuron. PMID- 8207423 TI - 4-Bromohomoibotenic acid selectively activates a 1-aminocyclopentane-1S,3R dicarboxylic acid-insensitive metabotropic glutamate receptor coupled to phosphoinositide hydrolysis in rat cortical slices. AB - Glutamate activates a family of receptors, known as metabotropic glutamate receptors (mGluRs), that are coupled to various second messenger systems through G proteins. All mGluR subtypes characterized to date in rat brain slices are activated by the glutamate analogue 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD). However, few agonists are available that selectively activate specific mGluR subtypes. We report that the glutamate analogue (R,S)-4 bromohomoibotenate (BrHI) stimulates phosphoinositide hydrolysis in rat cerebral cortical slices in a concentration-dependent manner (EC50 = 190 microM). The response to BrHI is stereoselective and is not blocked by ionotropic glutamate receptor antagonists. It is interesting that the responses to BrHI and 1S,3R-ACPD are completely additive, suggesting that these responses are mediated by different receptor subtypes. Consistent with this, the response to BrHI is insensitive to L-2-amino-3-phosphonopropionic acid (L-AP3), whereas the response to 1S,3R-ACPD is partially blocked by L-AP3. BrHI does not activate metabotropic receptors coupled to changes in cyclic AMP accumulation or activation of phospholipase D. Thus, BrHI seems to activate specifically a phosphoinositide hydrolysis-linked mGluR that is insensitive to 1S,3R-ACPD. This compound may prove useful as a tool for elucidating the roles of different mGluR subtypes in mammalian brain. PMID- 8207424 TI - Characterization, distribution, and protein kinase C-mediated regulation of [35S]glutathione binding sites in mouse and human spinal cord. AB - We have characterized a high-affinity [35S]-glutathione ([35S]GSH) binding site in mouse and human spinal cord. [35S]GSH binding sites in mouse and human spinal cord were observed largely within the gray matter in both the dorsal and ventral horns of spinal cord at cervical, thoracic, and lumbosacral segments. High affinity [35S]GSH binding was saturable, showing a Bmax of 72 fmol/mg of protein and a KD of 3.0 nM for mouse spinal cord and a Bmax of 52 fmol/mg of protein and a KD of 1.6 nM for human spinal cord. [35S]GSH binding was displaceable by GSH, L cysteine, and S-hexyl-GSH, but not by glutamate, glycine, or NMDA. These [35S]GSH binding sites exhibited kinetic and saturation characteristics similar to GSH binding sites in rat brain astrocytes. To determine whether [35S]GSH binding sites could be regulated by protein kinase C, we exposed human spinal cord sections to phorbol 12,13-diacetate for 1 h before ligand binding. Phorbol ester treatment increased [35S]GSH binding by approximately 60%, an effect that could be blocked by exposure of spinal cord sections to 1-(5-isoquinolinylsulfonyl)-2 methylpiperazine, a general protein kinase inhibitor. [35S]GSH binding sites in the spinal cord of both species exhibited many of the characteristics of a receptor including saturable binding, high affinity, ligand specificity, and modulation by kinase activity. These data suggest that GSH is a neurotransmitter in the CNS. PMID- 8207425 TI - Activation of opioid and muscarinic receptors stimulates basal adenylyl cyclase but inhibits Ca2+/calmodulin- and forskolin-stimulated enzyme activities in rat olfactory bulb. AB - In rat olfactory bulb, muscarinic and opioid receptor agonists stimulate basal adenylyl cyclase activity in a GTP-dependent and pertussis toxin-sensitive manner. However, in the present study, we show that in the same brain area activation of these receptors causes inhibition of adenylyl cyclase activity stimulated by Ca2+ and calmodulin (CaM) and by forskolin (FSK), two direct activators of the catalytic unit of the enzyme. The opioid and muscarinic inhibitions consist of a decrease of the maximal stimulation elicited by either CaM or FSK, without a change in the potency of these agents. [Leu5]-Enkephalin and selective delta- and mu-, but not kappa-, opioid receptor agonists inhibit the FSK stimulation of adenylyl cyclase activity with the same potencies displayed in stimulating basal enzyme activity. Similarly, the muscarinic inhibition of FSK-stimulated adenylyl cyclase activity shows agonist and antagonist sensitivities similar to those characterizing the muscarinic stimulation of basal enzyme activity. Fluoride stimulation of adenylyl cyclase is not affected by either carbachol or [Leu5]enkephalin. In vivo treatment of olfactory bulb with pertussis toxin prevents both opioid and muscarinic inhibition of Ca2+/CaM- and FSK-stimulated enzyme activities. These results indicate that in rat olfactory bulb delta- and mu-opioid receptors and muscarinic receptors, likely of the M4 subtype, can exert a dual effect on cyclic AMP formation by interacting with pertussis toxin-sensitive GTP-binding protein(s) and possibly by affecting different molecular forms of adenylyl cyclase. PMID- 8207426 TI - Muscarinic receptor-mediated inositol 1,4,5-trisphosphate formation in SH-SY5Y neuroblastoma cells is regulated acutely by cytosolic Ca2+ and by rapid desensitization. AB - Stimulation of muscarinic receptors expressed in SH-SY5Y human neuroblastoma cells resulted in a complex profile of inositol 1,4,5-trisphosphate (InsP3) accumulation, with a dramatic increase (six- to eightfold) over the first 10 s (the "peak" phase) and subsequently from approximately 60 s onward, maintained at a lower but sustained level (the "plateau" phase). Chelation of extracellular Ca2+ with EGTA or inhibition of Ca2+ channels with Ni2+ showed that the plateau phase was dependent upon Ca2+ entry. Furthermore, use of thapsigargin and EGTA to discharge and sequester Ca2+ from intracellular stores revealed that Ca2+ from this source was capable of supporting the peak phase of the InsP3 response. Carbachol-stimulated phosphoinositidase C activity in permeabilized SH-SY5Y cells was also shown to be highly dependent on free Ca2+ concentration (20-100 nM) and suggests that under normal conditions, InsP3 formation is enhanced by increases in cytosolic free Ca2+ concentration that accompany muscarinic receptor activation. Measurement of carbachol-stimulated total inositol phosphate accumulation in the presence of Li+ indicated that the initial rate of phosphoinositide hydrolysis (from 0 to 30 s) was about fivefold greater than that from 30 to 300 s. This rapid but partial desensitization of receptor-mediated phosphoinositide hydrolysis provides strong evidence for the mechanism underlying the changes in InsP3 accumulation over this time. Because very similar data were obtained in Chinese hamster ovary cells transfected with human m3 receptor cDNA, we suggest that although increases in cytosolic free CA2+ concentration amplify InsP3 formation during stimulation of m3 muscarinic receptors, the primary factor that governs the profile of InsP3 accumulation is rapid, but partial, desensitization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207427 TI - Stable expression of the cloned rat brain neurotensin receptor into fibroblasts: binding properties, photoaffinity labeling, transduction mechanisms, and internalization. AB - The study of the pharmacological, biochemical, and transduction properties of the cloned rat brain neurotensin receptor was carried out in thymidine kinase mutant fibroblasts stably transfected with the receptor cDNA. The interaction of neurotensin with transfected fibroblasts leads to a concentration-dependent stimulation of phosphatidylinositol hydrolysis and intracellular calcium. These effects are totally inhibited by the nonpeptide neurotensin antagonist SR48692. By contrast, this receptor remains unable to modulate intracellular levels of cyclic nucleotides. The transfected neurotensin receptor can be solubilized in an active form by digitonin with an identical pharmacological profile, whereas the detergent 3-[(3-cholamidopropyl) dimethylammonio]-1-propane-sulfonic acid is unable to solubilize the binding activity. The binding of iodinated neurotensin to transfected fibroblasts bearing the cloned receptor remains partly un dissociated even after an acid washing step, indicating that the transfected neurotensin receptor retains the capacity to be internalized according to a temperature-dependent mechanism. Indeed, the sequestration of the neurotensin receptor complex can be blocked by phenylarsine oxide. Finally, photoaffinity labeling experiments reveal that the cloned rat brain neurotensin receptor is expressed under two forms with molecular masses of 50 and 60 kDa. Labeling and internalization of these two proteins are totally blocked by the neurotensin antagonist SR48692. PMID- 8207428 TI - Evidence that extracellular concentrations of dopamine are regulated by noradrenergic neurons in the frontal cortex of rats. AB - Experiments were performed to confirm that noradrenergic terminals regulate extracellular concentrations of dopamine (DA) in the frontal cortex of rats. The effects of 20 mg/kg 1-[2-[bis(4-fluorphenyl)methoxy]-ethyl]-4-(3- phenylpropyl)piperazine (GBR 12909), a selective inhibitor of DA uptake, and 2.5 mg/kg desipramine (DMI) on the extracellular concentrations of DA in the frontal cortex and striatum were studied in rats given 6-hydroxydopamine (6 micrograms/microliters) bilaterally into the locus coeruleus to destroy noradrenergic terminals. GBR 12909 increased dialysate DA similarly in the striatum of vehicle and 6-hydroxydopamine-treated rats, whereas in the frontal cortex it raised DA concentrations only in lesioned animals. DMI raised extracellular DA concentrations in the frontal cortex but not in the striatum of controls. The effect of DMI on cortical DA was abolished by the 6-hydroxydopamine lesion. GBR 12909, at a subcutaneous dose of 20 mg/kg, further increased cortical dialysate DA in rats given DMI intraperitoneally at 20 mg/kg or through the probe at 10(-5) mol/L. The data support the hypothesis of an important regulation of the extracellular concentrations of DA in the frontal cortex by noradrenergic terminals. PMID- 8207429 TI - Temperature sensitivity of agonist high-affinity binding sites of solubilized and reconstituted D1 dopamine receptors. AB - Solubilization of rat striatal membranes with sodium cholate, followed by reconstitution into phospholipid vesicles, leads to a 6.5-fold increase in the agonist high-affinity binding sites of the D1 dopamine receptor. These high affinity binding sites display differential sensitivity toward temperature. When reconstituted receptors were preincubated for 1 h at 0-4 degrees C (on ice) or at 22 degrees C (room temperature) followed by radioligand binding assays with dopamine, neither the high-affinity values of the receptor for dopamine nor the percent receptors in the high-affinity state (31-39%) were changed from control reconstituted receptors, which were not subject to any preincubations. At 30 degrees C, there was a partial loss in the number of high-affinity D1 receptors with only 25% of the total receptor population in the high-affinity state; there was no change in the affinity values of the high-affinity binding sites. At 37 degrees C, there was a 40% loss in total number of D1 receptor binding sites. All the high-affinity binding sites were lost and the remaining 60% of binding activity represented the low-affinity binding state of the receptor. These results indicate that the high-affinity binding sites of the reconstituted D1 dopamine receptors are uniquely sensitive to higher temperatures. PMID- 8207430 TI - Excitatory and inhibitory effects of A1 and A2A adenosine receptor activation on the electrically evoked [3H]acetylcholine release from different areas of the rat hippocampus. AB - The modulation by adenosine analogues and endogenous adenosine of the electrically evoked release of [3H]acetylcholine ([3H]ACh) was compared in subslices of the three areas of the rat hippocampus (CA1, CA3, and dentate gyrus). The mixed A1/A2 agonist 2-chloroadenosine (CADO; 2-10 microM) inhibited, in a concentration-dependent manner, the release of [3H]ACh from the three hippocampal areas, being more potent in the CA1 and CA3 areas than in the dentate gyrus. The inhibitory effect of CADO (5 microM) on [3H]ACh release was prevented by the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 50 nM) in the three hippocampal areas and was converted in an excitatory effect in the CA3 and dentate gyrus areas. The A2A agonist CGS-21680 (30 nM) produced a greater increase of the evoked release of [3H]ACh in the CA3 than in the dentate gyrus areas, whereas no consistent effect was found in the CA1 area or in the whole hippocampal slice. The excitatory effect of CGS-21680 (30 nM) in the CA3 area was prevented by the adenosine receptor antagonist 3,7-dimethyl-1-propargylxanthine (10 microM). Both adenosine deaminase (2 U/ml) and DPCPX (250 nM) increased the evoked release of [3H]ACh in the CA1 and CA3 areas but not in the dentate gyrus. The amplitude of the effect of DPCPX and adenosine deaminase was similar in the CA1 area, but in the CA3 area DPCPX produced a greater effect than adenosine deaminase. It is concluded that the electrically evoked release of [3H]ACh in the three areas of the rat hippocampus can be differentially modulated by adenosine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207431 TI - Increased activation of L-type voltage-dependent calcium channels is associated with glycine enhancement of N-methyl-D-aspartate-stimulated dopamine release in global cerebral ischemia/reperfusion. AB - We investigated the relationships among N-methyl-D-aspartate, glycine, L-type voltage-dependent calcium channels, and [3H]dopamine release in a canine model of global cerebral ischemia/reperfusion. The binding of [3H]PN200-110 ([3H]isradipine) to L-type voltage-dependent calcium channels, that open as a consequence of N-methyl-D-aspartate-induced changes in membrane potential, was approximately doubled in striatal membranes prepared from ischemic animals relative to controls, and remained significantly elevated at 30 min and 2 h of reperfusion. These changes coincided temporally with changes in the ability of the voltage-sensitive calcium channel blocker nitrendipine to inhibit glycine enhancement of N-methyl-D-aspartate-stimulated [3H]dopamine release in striatal slices prepared from the same animals. Compared with nonischemic controls, N methyl-D-aspartate-stimulated [3H]dopamine release was increased in ischemic animals and remained increased throughout reperfusion up to at least 24 h. Glycine enhanced N-methyl-D-aspartate-stimulated release in all treatment groups. The enhancement of N-methyl-D-aspartate-stimulated dopamine release by glycine was reduced by the inclusion of nitrendipine in striatal slices from ischemic and 30-min reperfused animals. These data suggest that glycine may facilitate opening of the voltage-dependent calcium channels activated by N-methyl-D-aspartate and that this facilitation is blocked by the antagonist nitrendipine. PMID- 8207432 TI - Detection of superoxide production by activated microglia using a sensitive and specific chemiluminescence assay and microglia-mediated PC12h cell death. AB - Superoxide production by cultured microglia derived from neonatal rat brains and the cytotoxicity of these cells were evaluated. The chemiluminescence (photon counts) detected in the presence of MCLA, a new chemiluminescence probe, was strongly correlated with the microglial cell count. Chemiluminescence observed in this system was confirmed to originate specifically from superoxide produced by activated microglia. Phorbol myristate acetate-stimulated microglia caused a pronounced reduction of PC12h cell numbers in coculture. The addition of superoxide dismutase with catalase or the addition of deferoxamine mesylate inhibited PC12h cell death, suggesting that active oxygen species derived from superoxide generated by the microglia or iron-oxygen complex formation were responsible for the cytotoxicity. These results imply that activated microglia may participate in the progression of the pathologic process in some neurodegenerative disorders. PMID- 8207433 TI - Extension of the 2-deoxyglucose method to the fetus in utero: theory and normal values for the cerebral glucose consumption in fetal guinea pigs. AB - Fetal cerebral metabolism changes during development. The normal fetal metabolic rate must be known to evaluate pathophysiological changes. Therefore, we determined the regional cerebral glucose consumption in the fetal guinea pig. This required the application of the 2-deoxyglucose method to this species. We measured both the transfer coefficients of deoxyglucose and glucose between the maternal arterial plasma and the fetal brain and the lumped constant in chronically prepared undisturbed guinea pig dams using a three-compartment model. Furthermore, the ratio between the initial clearances of deoxyglucose and glucose between the maternal arterial plasma and the fetal brain and the ratio between the phosphorylation coefficients of these substrates in the fetal brain were determined. The total cerebral glucose consumption measured by the deoxyglucose method (10 +/- 1.2 mumol/100 g/min) was similar to that calculated from the glucose concentration and the phosphorylation coefficient of glucose in the cerebrum (10 +/- 0.4 mumol/100 g/min). We conclude that the 2-deoxyglucose method is applicable to the guinea pig, and we further conclude that in the fetal guinea pig cerebral glucose consumption is 10 times lower than that in the adult. PMID- 8207434 TI - Early effects of beta,beta'-iminodipropionitrile on tubulin solubility and neurofilament phosphorylation in the axon. AB - To elucidate the role of neurofilaments in microtubule stabilization in the axon, we studied the effects of beta,beta'-iminodipropionitrile (IDPN) on the solubility and transport of tubulin as well as neurofilament phosphorylation in the motor fibers of the rat sciatic nerve. IDPN is known to impair the axonal transport of neurofilaments, causing accumulation of neurofilaments in the proximal axon and segregation of neurofilaments to the peripheral axoplasm throughout the nerve. Administration of IDPN at various intervals after radioactive labeling of the spinal cord with L-[35S]methionine revealed that transport inhibition occurred all along the nerve within 1-2 days. Transport of cold-insoluble tubulin, which accounts for 50% of axonal tubulin, was also affected. A significant increase in the proportion of cold-soluble tubulin was observed, reaching a maximum at 3 days after IDPN treatment and returning to the control level in the following weeks. Preceding this change in tubulin solubility, a transient decrease in the phosphorylation level of the 200-kDa neurofilament protein was detected in the ventral root using phosphorylation dependent antibodies. These early changes agreed in timing with the onset of segregation and transport inhibition, suggesting that interaction between neurofilaments and microtubules possibly regulated by phosphorylation plays a significant role in microtubule stabilization. PMID- 8207435 TI - In situ hybridization evidence of differential modulation by pentobarbital of GABAA receptor alpha 1- and beta 3-subunit mRNAs. AB - Tolerance to and withdrawal from pentobarbital were induced in rats by continuous intracerebroventricular infusion via subcutaneously implanted osmotic minipumps. In situ hybridization of GABAA receptor alpha 1- and beta 3-subunit mRNA was conducted using synthetic 3'-end 35S-dATP-labeled oligodeoxynucleotide probes. Results were quantified by film densitometry. In animals that were tolerant to pentobarbital, levels of alpha 1-subunit mRNA were decreased in hippocampus, superior colliculus, and inferior colliculus, but levels of beta 3-subunit mRNA were not affected. Dramatically increased levels of GABAA receptor subunit mRNA were observed in animals 24 h after withdrawal from chronic pentobarbital treatment. These increases occurred in cerebral cortex and cerebellum for the alpha 1 subunit and in cerebral cortex only for the beta 3-subunit. These data provide further support to the structural and pharmacological GABAA receptor heterogeneity in discrete brain areas. The observed changes of subunit expression may underlie, at least in part, the receptor up- and down-regulation observed in receptor ligand binding studies. PMID- 8207436 TI - Novel inactive and distinctively glycosylated forms of butyrylcholinesterase from chicken serum. AB - Three different homologues of butyrylcholinesterase (BChE) with 75-, 62-, and 54 kDa subunit size are isolated from adult chicken serum, and all show very low or zero enzyme activity. Although the active BChE from serum with a subunit size of 81 kDa forms tetramers, the 75-kDa protein is isolated as a dimer. The homology of the 75-kDa protein with active BChE is shown by immunoreactivity with BChE specific monoclonal antibodies, by coisolation with the active BChE, and by their identical first six N-terminal amino acids. By deglycosylation of these proteins and by their differential lectin binding, we show that the active BChE is an N glycosylated protein of the triantennary type, whereas the inactive 75-kDa protein is O-glycosylated. These data show for the first time the existence of (1) multiple inactive forms of BChE, (2) secreted inactive cholinesterases, because they are found in serum, and (3) an O-glycosylated cholinesterase. Because cholinesterases can regulate neurite growth in vitro by a nonenzymatic mechanism, these data strongly support that both inactive and active forms of BChE may be involved in noncholinergic communication, possibly depending on particular glycosylation patterns. PMID- 8207437 TI - Correlative regulation of nerve growth factor level and choline acetyltransferase activity by thyroxine in particular regions of infant rat brain. AB - Effects of thyroxine (T4) on nerve growth factor (NGF) level and choline acetyltransferase (ChAT) activity of rat brains were investigated. Repetitive intraperitoneal administration of T4 caused increases in both NGF level and ChAT activity in the frontal cortex, septum, hippocampus, and striatum and decreases in the cerebellum in 2-day-old rats. Only ChAT activity was elevated in the olfactory bulb, and the NGF level remained unchanged there. No changes were observed in the midbrain and pons/medulla. Furthermore, T4 was effective on the postnatal rats only up to day 11. These results suggest that T4 plays a role in the developmental regulation of NGF level and ChAT activity in rat brain in a region- and/or stage-specific manner. That (1) changes in NGF level and ChAT activity occurred in regions nearly identical to those that contained NGF responding neurons, and (2) the change in NGF level in the hippocampus and frontal cortex was followed by the change of ChAT activity after a single injection of T4 suggest that the effects of T4 on cholinergic differentiation are, at least in part, mediated via NGF, which itself is quantitatively regulated by T4. PMID- 8207438 TI - Vasoactive intestinal peptide and forskolin stimulate interleukin 6 production by rat cortical astrocytes in culture via a cyclic AMP-dependent, prostaglandin independent mechanism. AB - In this study we analyzed the involvement of the cyclic AMP (cAMP)-protein kinase A system in the regulation of interleukin 6 production by cultured cortical astrocytes. Vasoactive intestinal peptide strongly increased, in a dose-dependent manner, interleukin 6 production. This effect was reduced when protein kinase A was blocked by KT-5720; it was not affected by calphostin C, a protein kinase C inhibitor. Forskolin caused a concentration-dependent increase in interleukin 6 release that was also inhibited by KT-5720. Because prostaglandins are believed to play a role in interleukin 6 production, we tried to determine whether the stimulatory effects of vasoactive intestinal peptide and forskolin on cytokine release might be mediated by stimulation of prostaglandin production in cortical astrocytes. Vasoactive intestinal peptide did not increase the production of either prostaglandin E2 or F2 alpha. Conversely, forskolin concentration dependently stimulated the production of both prostaglandins, an effect that was blocked by indomethacin. Indomethacin did not affect either vasoactive intestinal peptide- or forskolin-stimulated interleukin 6 production. To exclude the possibility that prostaglandins participate in interleukin 6 production induced by forskolin, we tested prostaglandins E2 and F2 alpha. The former was completely ineffective in eliciting the cytokine production, whereas prostaglandin F2 alpha slightly increased interleukin 6 production only at the highest concentrations. 8 Bromo-cAMP and dibutyryl-cAMP stimulated interleukin 6 production to a lesser extent than vasoactive intestinal peptide and forskolin. In conclusion, we provide evidence that vasoactive intestinal peptide increases interleukin 6 production by astrocytes through the stimulation of the cAMP-protein kinase A pathway, an effect that is reproduced by cAMP analogues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207439 TI - Up-regulation of carbonic anhydrase isozyme IV in CNS myelin of mice genetically deficient in carbonic anhydrase II. AB - Carbonic anhydrase (CA) II is the major CA isozyme in the brain, where it participates in acid-base homeostasis, fluid transport, and myelin synthesis. The CA II deficiency [CA(II)D] mutation in the mouse results in structural changes in the glial cells in the CNS and in decreased susceptibility to seizures, but no detectable changes in myelin yield and ultrastructure. We compared the CA isozymes in brain and spinal cord fractions, as well as in purified myelin, between CA(II)D and control mice. CA(II)D resulted in a much lower total CA specific activity in all tissues examined but in higher CA IV specific activities in soluble and membrane-associated fractions and pure myelin. Western blots of purified myelin showed a band corresponding to CA IV in CA(II)D mice. This band was weak or undetectable in myelin samples from normal mice. Immunocytochemical staining demonstrated CA IV in oligodendrocytes and myelinated tracts in normal mouse brains and stronger staining of the same structures in brains of CA(II)D mutants. We conclude that CA(II)D mutation in the mouse up-regulates CNS CA IV. We speculate that this up-regulation could mitigate the effect of CA(II)D on myelin formation and maintenance. PMID- 8207440 TI - The subunit composition of a GABAA/benzodiazepine receptor from rat cerebellum. AB - The pentameric subunit composition of a large population (36%) of the cerebellar granule cell GABAA receptors that show diazepam (or clonazepam)-insensitive [3H]Ro 15-4513 binding has been determined by immunoprecipitation with subunit specific antibodies. These receptors have alpha 6, alpha 1, gamma 2S, gamma 2L, and beta 2 or beta 3 subunits colocalizing in the same receptor complex. PMID- 8207441 TI - Preferential stimulation of extracellular release of dopamine in rat frontal cortex to striatum following competitive inhibition of the N-methyl-D-aspartate receptor. AB - Using a brain microdialysis technique, we have shown in the rat that local infusion of a selective and competitive N-methyl-D-aspartate (NMDA) receptor antagonist, cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS-19755), into the medial frontal cortex via dialysis tubing caused a concentration-related increase in the extracellular release of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the cortical region. Coinfusion of a sodium channel blocker, tetrodotoxin, completely inhibited the ability of the NMDA antagonist to augment frontal dopamine metabolism. These findings suggest that dopamine neurons projecting to the frontal cortex might be under a tonic transsynaptic inhibition exerted by excitatory amino acid neurotransmission via the NMDA receptor at the level of dopamine terminal fields. PMID- 8207442 TI - NMDA and nitric oxide increase microtubule-associated protein 2 gene expression in hippocampal granule cells. AB - Microtubule-associated protein 2 (MAP2), a component of the neuronal cytoskeleton, has attracted attention as a possible cellular substrate linking hippocampal N-methyl-D-aspartate (NMDA) receptor stimulation to alterations in cellular morphology. We show here that microinjection of NMDA, 8-bromo-cyclic GMP, or sin-1 molsidomine (which spontaneously releases nitric oxide), onto the molecular layer of the hippocampal dentate gyrus, increased the levels of MAP2 mRNA in the affected granule cells. No changes were observed in the levels of mRNAs encoding several other cytoskeletal components. This shows that hippocampal NMDA receptor stimulation can potentially initiate a long-term alteration in dendritic structure by affecting MAP2 gene expression and provides the first evidence that nitric oxide release in vivo, acting through cyclic GMP-dependent protein kinase, can cause long-term changes in neuronal function by modulating gene expression. PMID- 8207443 TI - Methylmercury-induced elevations in intrasynaptosomal zinc concentrations: an 19F NMR study. AB - Methylmercury (MeHg) increases the concentration of intracellular Ca2+ ([Ca2+]i) and another endogenous polyvalent cation in both synaptosomes and NG108-15 cells. In synaptosomes, the elevation in [Ca2+]i was strictly dependent on extracellular Ca2+ (Ca2+e); similarly, in NG108-15 cells, a component of the elevations in [Ca2+]i was Ca2+e dependent. The MeHg-induced elevations in endogenous polyvalent cation concentration were independent of Ca2+e in synaptosomes and NG108-15 cells. The pattern of alterations in fura-2 fluorescence suggested the endogenous polyvalent cation may be Zn2+. Using 19F-NMR spectroscopy of rat cortical synaptosomes loaded with the fluorinated chelator 1,2-bis(2-amino-5 fluorophenoxy)ethane-N,N,N',N'- tetraacetic acid (5F-BAPTA), we have determined unambiguously that MeHg increases the free intrasynaptosomal Zn2+ concentration ([Zn2+]i). In buffer containing 200 microM EGTA to prevent the Ca2+e-dependent elevations in [Ca2+]i, the [Zn2+]i was 1.37 +/- 0.20 nM; following a 40-min exposure to MeHg-free buffer [Zn2+]i was 1.88 +/- 0.53 nM. Treatment of synaptosomes for 40 min with 125 microM MeHg yielded [Zn2+]i of 2.69 +/- 0.55 nM, whereas 250 microM MeHg significantly elevated [Zn2+]i to 3.99 +/- 0.68 nM. No Zn2+ peak was observed in synaptosomes treated with the cell-permeant heavy metal chelator N,N,N',N'-tetrakis(2- pyridylmethyl)ethylenediamine (TPEN, 100 microM) following 250 microM MeHg exposure. [Ca2+]i in buffer containing 200 microM EGTA was 338 +/- 26 nM and was 370 +/- 64 nM following an additional 40-min exposure to MeHg-free buffer. [Ca2+]i was 498 +/- 28 or 492 +/- 53 nM during a 40-min exposure to 125 or 250 microM MeHg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207444 TI - Squid optic lobe synaptosomes: what can they tell us about presynaptic protein synthesis? PMID- 8207445 TI - Neural specificity of elav expression: defining a Drosophila promoter for directing expression to the nervous system. AB - The Drosophila melanogaster vital gene, embryonic lethal abnormal visual system (elav), is required for the postdeterminative development of the nervous system. Its gene product encodes an RNA binding protein that was found to be expressed in all neurons right after their birth. This specific, ubiquitous, and continuous pattern of neural expression has led to the increasingly popular use of ELAV protein as a neural-specific marker. To understand the molecular basis of this neural-specific expression, we have defined and analyzed the structure of the elav promoter. Cis-acting sequences important for conferring the neural specificity of elav expression were identified by analyzing the reporter gene expression in transformants carrying different elav-beta-galactosidase fusion genes. This analysis delimits a 333-bp region (-92 to +241) that is necessary for specifying the elav pattern of nervous system expression. A 3.5-kb promoter fragment encompassing this region was designed for targeting gene expression specifically to the nervous system and would be a useful tool for the analysis of nervous system function. PMID- 8207446 TI - Organization, sequence, and expression of a gene encoding goldfish neurofilament medium protein. AB - The goldfish visual pathway displays a remarkable capacity for continuous neurogenesis, plasticity, and regeneration. The intermediate filament protein composition of this system differs from that of higher vertebrates, which lack the capacity for continued nerve growth and development. In an effort to determine how intermediate filament proteins are regulated during nerve growth, we isolated and characterized cDNA and genomic clones representing the goldfish neurofilament medium (NF-M) protein. The tissue-specific expression of goldfish NF-M mRNA was analyzed by RNase protection assays and by in situ hybridization. The expression of goldfish NF-M is qualitatively the same as in other species. Although the intermediate filament protein composition of the goldfish visual pathway is unusual when compared with higher vertebrates, the goldfish NF-M protein is similar to higher vertebrate NF-M proteins. In addition, the organization of the goldfish NF-M gene is identical to the NF-M genes in all other vertebrate species. In contrast, the promoter region of the goldfish NF-M gene has several potential regulatory sequences that are not found in the promoter regions of higher vertebrate NF-M genes. PMID- 8207447 TI - Carbohydrate-binding proteins in the leech: I. Isolation and characterization of lactose-binding proteins. AB - Three lactose-binding proteins with apparent molecular masses of 16, 35, and 63 kDa [leech lectin 16, 35, and 63 (LL,16, LL35, and LL63, respectively)] were isolated from leech membranes. Polyclonal antibodies raised against LL35 cross reacted with LL16 and LL63, indicating that all three lectins were immunologically related. These leech lectins, however, can be subdivided into two groups based on their tissue distributions and binding affinities for galactose derivatives. LL16 and LL35 are endogenous to the leech's CNS, whereas LL63 is only present in peripheral organs. LL16 and LL35, found in the CNS, bind both the alpha and beta anomers of methylgalactose, whereas the peripheral lectin LL63 binds only the beta form. LL35 and LL63 also differ in their binding affinities for galactosamine and N-acetylgalactosamine. The binding activity of LL35 was calcium independent and active over a wide pH range. Triton X-100 and 2 mercaptoethanol were necessary to recover LL35 binding activity during extraction. These characteristics strongly suggest that LL35 is another member of the calcium-independent galactose/lactose-specific lectins previously described in vertebrates and recently demonstrated in sponges and nematodes. Because a single leech expresses up to 100 micrograms of LL35, this leech lectin is readily amenable to structural and functional analysis. PMID- 8207448 TI - Carbohydrate-binding proteins in the leech: II. Lactose-binding protein LL35 is located to neuronal and muscle subsets and all epithelial cells. AB - Leech lectin 35 (LL35) is a calcium-independent galactoside-binding protein with a molecular mass of 35 kDa and binding properties similar to those of calcium independent, galactose-specific lectins found in vertebrates, sponges, and nematodes. LL35 was initially isolated from membranes of the leech CNS; however, large amounts of this lectin were also extracted from the rest of the leech. Using affinity-purified antibodies to LL35, we report the immunocytochemical localization of LL35 in adult and embryonic leech. LL35 is developmentally regulated in epithelial, neuronal, and muscle tissue but is absent from glia. During embryogenesis, LL35 is highly expressed by a subset of sensory neurons, weakly expressed in epithelial cells, and absent from muscle. In the adult, LL35 is still present on the same sensory neurons but has become more abundant in epithelial cells lining the CNS and peripheral organs. LL35 also appeared on a muscle cell specifically located in the CNS but remained absent from peripheral muscle. The developmentally regulated distribution of LL35 in epithelial cells, neurons, and CNS muscles suggests a multifunctional role for this lectin with respect to these different cell types. PMID- 8207449 TI - Serotonin binding protein: synthesis, secretion, and recycling. AB - Serotonin binding protein (SBP) is present in all neurectodermally derived cells that store serotonin (5-HT). Three forms of SBP have been detected (68, 56, and 45 kDa), and antibodies to SBP that interfere with the binding of 5-HT react with each of these proteins. The current experiments test two hypotheses: (a) that the 56- and 45-kDa forms of SBP are produced by posttranslational cleavage of a 68 kDa precursor molecule; and (b) that 45-kDa SBP is a constituent of serotonergic secretory vesicles. Pulse-chase experiments were carried out using medullary thyroid carcinoma cells as a model. These neurectodermally derived cells produce 5-HT and all three forms of SBP. Following pulse labeling for 20 min with L [35S]methionine, the cells were incubated in the presence of an excess of unlabeled L-methionine for 0, 30, 60, or 90 min at 37 degrees C. Alternatively, the chase was performed under conditions (20 degrees C, inhibition of ATP generation) that delay or stop transport of newly synthesized proteins from the rough endoplasmic reticulum through the Golgi apparatus. Following incubation, the cells were washed and solubilized, and SBP was immunoprecipitated. Radioactive proteins in the immunoprecipitate were electrophoretically resolved and quantified. Immediately after the pulse, each of the three forms of SBP was found to be labeled with 35S. The relative proportions of 35S-labeled 68-, 56-, and 45-kDa SBP remained the same at each interval of chase. These proportions were not changed when the chase was carried out at 20 degrees C or under conditions that blocked the biosynthesis of ATP. These observations suggest that each form of SBP is a primary product of translation, that the smaller forms of SBP are not produced by cleavage from a larger molecule, and that the size of the primary products of translation is not altered by passage to the Golgi apparatus or a post-Golgi compartment. When secretion was induced, 45-kDa SBP, but not 56- or 68-kDa SBP, was released to the medium. When antibodies to 45-kDa SBP were added to the medium at the time secretion was induced, antibody binding sites appeared as patches on the cell surfaces. Because of these sites, cells were lysed when they were stimulated to secrete in the presence of antibodies to 45 kDa SBP and guinea pig complement.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8207450 TI - A breathing circuit alarm system based on neural networks. AB - OBJECTIVE: The objectives of our study were (1) to implement intelligent respiratory alarms with a neural network; and (2) to increase alarm specificity and decrease false-alarm rates compared with current alarms. METHODS: We trained a neural network to recognize 13 faults in an anesthesia breathing circuit. The system extracted 30 breath-to-breath features from the airway CO2, flow, and pressure signals. We created training data for the network by introducing 13 faults repeatedly in 5 dogs (616 total faults). We used the data to train the neural network using the backward error propagation algorithm. RESULTS: In animals, the trained network reported the alarms correctly for 95.0% of the faults when tested during controlled ventilation, and for 86.9% of the faults during spontaneous breathing. When tested in the operating room, the system found and correctly reported 54 of 57 faults that occurred during 43.6 hr of use. The alarm system produced a total of 74 false alarms during 43.6 hr of monitoring. CONCLUSION: Neural networks may be useful in creating intelligent anesthesia alarm systems. PMID- 8207451 TI - Fuzzy-logic control of blood pressure through enflurane anesthesia. AB - OBJECTIVE: The objective of our study was to construct a closed-loop blood pressure control system using fuzzy logic during enflurane anesthesia. METHODS: Direct systolic blood pressure (SBP), the input variable, was assessed by a special fuzzy-logic membership function--that is, a triangulate continuum of grades between 0 and 1. We also set up the output membership function for the inhaled enflurane concentration. Four fuzzy-rule maps, or matrices, which determined the relationship between the changes of input variables and output values, were constructed based on published anesthetic values. The first map was based on the end-tidal anesthetic concentration known to block an adrenergic response. The fourth map was derived from the anesthetic effective dose (AD95). Fuzzy inference, arrived at by using fuzzy logic, followed the minimum-maximum center of gravity method. Anesthetic control started with the first map and was maintained with the succeeding maps. RESULTS: During anesthesia, the SBP remained within +/- 20% of the preanesthetic SBPs in 82% of the fuzzy control cases and within 83% during manual control. The difference was not significant. CONCLUSION: The anesthetist's management of the administration of the inhaled anesthetic enflurane was imitated by fuzzy-logic control of the blood pressure. PMID- 8207452 TI - Accuracy of beat-to-beat noninvasive measurement of finger arterial pressure using the Finapres: a spectral analysis approach. AB - OBJECTIVE: Our objective was to test the accuracy of noninvasive recordings of finger arterial pressure (FAP) using the Ohmeda Finapres (Ohmeda Monitoring Systems, Englewood, CO). METHODS: Twenty patients, aged 20 to 78 years, requiring admission to the intensive care unit and placement of intraarterial catheters participated in the study. Systolic and diastolic pressures were derived from 1 hr recordings of beat-to-beat FAP and from ipsilaterally recorded intraarterial pressure (IAP) signals. In all 20 cases, we analyzed beat-to-beat discrepancies between the actual magnitude of FAP and IAP, as well as the distribution of the consecutive differences within each of the two signals. In 10 cases, spectral analysis of the frequency content of both signals was performed. RESULTS: The average systolic FAP (128.1 +/- 22.4 mm Hg) did not differ from IAP (127.1 +/- 19.7 mm Hg), whereas diastolic FAP (78.1 +/- 11.9 mm Hg) was greater (71.5 +/- 10.3 mm Hg) (p < 0.001). No differences in the linear trends of FAP and IAP were observed. Overall, systolic FAP and IAP were discrepant by 0.84 +/- 13.3 mm Hg ( 21.82 to 25.8 mm Hg); diastolic FAP and IAP were discrepant by 6.67 +/- 5.23 mm Hg (2.68 to 13.05 mm Hg). Despite discrepancies in the magnitude of the two signals, the contour of IAP approximated that of FAP. Spectral analysis demonstrated good reproducibility and coherence between diastolic IAP and FAP fluctuations in both low-frequency (0.01 to 0.15 Hz) and high-frequency (0.15 to 0.33 Hz) bands. The low-frequency fluctuations in FAP systolic pressure were significantly amplified (p < 0.001) (gain 1.75), whereas the high-frequency fluctuations were not. CONCLUSIONS: Over the course of 1 hr, FAP followed the contour and frequency content of IAP. PMID- 8207453 TI - Agreement between large and small cuffs in sphygmomanometry: a quantitative assessment. AB - OBJECTIVE: The objective of this study is to quantify agreement and differences between blood pressure (BP) measurements by large cuffs (15 x 33 cm) and small cuffs (12 x 23 cm) in a representative sample of the U.S. population with varying arm circumferences. METHODS: The arm circumference and blood pressure (12 readings of each) of 85 subjects were measured, the latter with a mercury column sphygmomanometer. Data were classified according to arm circumference (small arm circumference, < or = 29 cm; large arm circumference, > 29 cm). Results were submitted to ANOVA, linear regression, difference between means (aggregate agreement), upper and lower limits of agreement at 95% confidence intervals, and intraclass correlation (individual-subject agreement/quantification of agreement). RESULTS: Small cuffs overestimated BP obtained from the large cuffs for the sample population as a whole, regardless of arm circumference. Limits of agreement at the lower end of 95% confidence interval were not clinically acceptable (SBP -1.56 to 11.05 mm Hg; DBP -2.06 to 8.63 mm Hg). However, measurements by both cuffs agreed among subjects with small arm circumferences (< or = 29 cm). CONCLUSION: Arm circumference plays an important role in determining proper cuff size for BP measurement. The small cuff overestimates BP in patients with large arm circumferences (> 29 cm), which represents more than 75% of the U.S. adult population. However, measurements of BP with the large cuff are not significantly different from those of small cuff measurements in subjects with small arm circumferences (< or = 29 cm). Therefore, we propose that the large cuff be used for routine BP measurement of the adults in the United States. PMID- 8207454 TI - Noninvasive automatic blood pressure machines in the PACU--is there a price? PMID- 8207455 TI - Automatic oscillometric NIBP (noninvasive automatic blood pressure machines) versus manual auscultatory blood pressure in the PACU. PMID- 8207456 TI - Fuzzy control in anesthesia. PMID- 8207457 TI - Monitoring normal and aberrant electrocardiographic activity from an endotracheal tube: comparison of the surface, esophageal, and tracheal electrocardiograms. AB - INTRODUCTION: We designed an endotracheal (ET) tube with orthogonally spaced ECG cuff electrodes. This ET tube was evaluated in dogs and sheep to determine (1) whether ECGs recorded from our tube were sufficient to make accurate clinical decisions concerning heart rate and rhythm; and (2) whether metallic cuff electrodes in direct contact with the trachea could induce mucosal burn injury during episodes of defibrillation. METHODS: Using experimental animals, we obtained ECGs from their tracheae and compared our findings with ECGs obtained from surface and esophageal electrodes. The electrical activity of the heart was modified by increasing the depth of anesthesia, occluding the left coronary artery, and administering beta-adrenergic drugs. Before the dogs were euthanized, they were subjected to episodes of transthoracic and intrathoracic defibrillation at energy levels of 200 to 400 J. A postmortem pathological examination of the trachea was performed to determine the incidence of mucosal burn injury. RESULTS: Tracheal electrocardiography provided valid information on heart-rate monitoring and certain morphology profiles. The R-R, PR, QRS, and QT intervals measured from the trachea had a correlation of 1.0, 0.96, 0.83, and 0.98, respectively, when compared with the same intervals obtained from surface electrodes. Two tracheae subjected to intrathoracic defibrillation at > 300 J revealed evidence of minor burn injury. Some localized epithelium loss was displayed in all tracheae; we attributed this to tracheal intubation. CONCLUSION: Tracheal electrocardiography may be useful in trauma patients who require intubation where injury precludes placement of chest ECG electrodes. PMID- 8207458 TI - Assessment of hypothermia with a new "tympanic" thermometer. AB - OBJECTIVE: Rapid and accurate core temperature measurement is vitally important in trauma patients, especially in those with accidental hypothermia. We tested a new aural thermometer to measure "tympanic" temperatures and assessed its accuracy during normothermic and hypothermic cardiopulmonary bypass. METHODS: Tympanic, esophageal, and blood temperatures were compared in 10 patients undergoing open-heart surgery. In addition, the stability and reaction time of the tympanic thermometer was evaluated in 5 volunteers in a cold room, with and without facial fanning. RESULTS: We observed a good linear correlation between tympanic and esophageal (r = 0.96) and blood (r = 0.81) temperature measurements during normothermia and hypothermia. There was no evidence of iatrogenic ear lesions in any of the patients. In the cold-room tests, stability was excellent and the time for adjustment of tympanic temperature measurement was about 2 min (with and without facial fanning). CONCLUSION: The new tympanic thermoprobe is a simple, fast, and reliable device for measuring core temperature. The device was designed particularly for, and may be useful for, patients suffering from accidental hypothermia. PMID- 8207459 TI - The effect of oral anticoagulant therapy on APTT results from a bedside coagulation monitor. AB - OBJECTIVE: The Ciba Corning 512 coagulation monitor (CC512) can be used to monitor heparin therapy by performing an activated partial thromboplastin time (APTT) at the patient's bedside. This study was designed to compare the CC512 results to results using the laboratory system. The relative sensitivities of both systems to the effect of oral anticoagulant therapy also was investigated. METHODS: Activated partial thromboplastin times were performed with both the CC512 and laboratory system on 74 specimens from patients receiving i.v. heparin therapy, and on 14 specimens from patients on warfarin only. Heparin assays were performed on 43 of the specimens from the heparinized patients. RESULTS: When a patient was receiving heparin only, the APTT results of the CC512 proved to be similar to existing laboratory methods. The CC512 APTT results of patients on warfarin only were markedly prolonged, whereas the laboratory APTTs were only slightly affected. CONCLUSION: The CC512 results were comparable to the laboratory system. However, the CC512 APTT was more sensitive to the effect of warfarin than the laboratory APTT system used in this study. CC512 APTT results on a patient receiving both oral and intravenous anticoagulation could be misleading. PMID- 8207460 TI - Cellular signals in atherosclerosis. AB - Atherosclerosis is a complex, incompletely understood process involving several cell types, including smooth muscle cells, endothelial cells, and platelets, and the signals between them. Atherosclerotic lesions result from an excessive inflammatory fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. Numerous growth regulatory molecules/factors participate in this process. This article reviews the atherosclerotic process and provides new scientific insights into the prevention and treatment of this disease. The implications for nursing are described. PMID- 8207461 TI - Cardiac allograft vasculopathy. AB - As the survival rates for cardiac transplant patients improve, the long-term complications of the procedure are becoming apparent. One such complication is a rapidly progressing form of coronary artery disease known as cardiac allograft vasculopathy (CAV). CAV is a major limiting factor in long-term graft survival. It is thought to develop immediately after transplantation, although initially it may be unrecognized because of a lack of sensitive screening techniques. It is estimated that 12% of cardiac transplant recipients will develop CAV each year after transplantation. Most researchers agree that CAV is primarily an immune related response to transplantation. However, other factors such as hyperlipidemia and obesity have also been implicated as predictors of CAV. This article explores the pathophysiology, risk factors, detection, and treatment of CAV in the cardiac transplant population. PMID- 8207462 TI - Endothelins: new players in cardiovascular physiology and disease. AB - Intercellular signaling is an important factor in cardiovascular regulation and the development of disease. The endothelins (ETs) are a recently described family of signaling peptides that appear to be important in cardiovascular regulation. Initial studies showed ET to be a potent vasoconstrictor of vascular smooth muscle. Subsequently, ET binding and activity have been demonstrated in a wide variety of tissues, including cardiac, venular, adrenal, and neural. Numerous studies have implicated the ETs in cardiovascular diseases such as hypertension, heart failure, and atherosclerosis. This article briefly reviews ET signaling pathways and the roles ET may play in cardiovascular regulation and disease. PMID- 8207463 TI - Cellular and molecular basis of epilepsy. PMID- 8207464 TI - Blue cones and cone bipolar cells share transcriptional specificity as determined by expression of human blue visual pigment-derived transgenes. AB - Sequences 5' of the human blue visual pigment gene have been assayed in transgenic mice for their ability to direct cell-type-specific expression of linked beta-galactosidase (lacZ) and placental alkaline phosphatase (P ALP1) reporters. Constructs containing either 5.4 kilobases (kb) or 0.47 kb of 5' flanking DNA direct expression exclusively to the retina. Within the retina, transgene expression is confined to blue cones and cone bipolar cells, as determined, respectively, by double labeling with anti-cone pigment antibodies and by morphologic analyses. These results imply that blue cones and cone bipolar cells have partially overlapping transcriptional specificities. PMID- 8207465 TI - Calcium wave fronts that cross gap junctions may signal neuronal death during development. AB - Embryonic anterior pagoda (AP) neurons in the leech interact with their segmental homologs in adjacent ganglia through transient axons that overlap during a critical period of development and then retract. However, when an AP neuron is ablated mechanically or by irradiation during this period, an adjacent homolog responds by reinitiating growth of its overlapped axon and thereby taking over vacated territory (Gao and Macagno, 1987b; Gao, 1989). The death of an AP cell is therefore communicated to its homolog, but the mechanism underlying this signaling is presently unknown. Since it was recently found that AP homologs are electrically and dye coupled through their transient axons (Wolszon et al., 1994), we investigated the possibility that gap junctions may mediate the cell death signal that could occur between developing neurons. Among several candidate intercellular signals, we began by studying calcium dynamics in embryonic AP cells, in situ, since calcium is known to cross gap junctions and is implicated in cell death in many systems. We found that elements that usually increase [Ca2+]i in adult neurons, such as releasable internal stores or voltage-dependent calcium channels, were not present at the critical period. Instead, mechanisms that reduce free calcium, such as buffering and pumping, were the most robust. When a large, focal calcium rise was produced in an AP axon by making a lesion with a UV microbeam (leading to eventual death of these neurons), calcium did not rise quickly throughout the cell, but rather moved in a slow (0.05-0.25 micron/sec) wave front away from the lesion site, into other processes of the damaged cell. Furthermore, when a calcium wave front reached the growth cone of a transient axon, it crossed at the gap junctions into the coupled axon of the neighboring AP neuron, but went no further. Since it is known that an AP responds to a neighbor's death by reinitiating growth only in that axon that contacts the dying cell (Gao and Macagno, 1987b; Gao, 1989), these observations are consistent with calcium playing a role in the signaling of cell death to homologs that are coupled to a dying cell. PMID- 8207466 TI - Fields in human motor areas involved in preparation for reaching, actual reaching, and visuomotor learning: a positron emission tomography study. AB - The purpose of this study was to examine the functional organization of motor cortices in the human brain involved in reaching and visuomotor learning. All subjects were asked to learn the positions of seven circular targets projected on a screen. Each time the targets were turned off, they were required to close their eyes and keep them closed, and, after a delay, to point to the center of the targets in a prescribed order using their right hand. The regional cerebral blood flow (rCBF) was measured with 15O-butanol and positron emission tomography in 20 subjects during a rest state, an initial learning stage, and a later learning stage. Ten subjects constituted the reaching group in which rCBF was measured during actual reaching; the 10 other subjects constituted the preparation group in which rCBF was measured in the delay period between target exposure and actual reaching. Individual subtraction images (each stage minus rest) were calculated and transformed into a standard size and shape brain image by the adjustable computerized brain atlas and averaged, after which significant changes of rCBF were identified. In all reaching and preparation for reaching phases, cortical fields were activated in the left primary motor area (M1) and the left premotor area (PMA). Within M1, fields active in the delay phases were adjacent to the fields active only during actual reaching movements. During the course of learning, additional fields of activity appeared in both M1 and PMA. The results indicate that three types of fields occur in M1 and PMA: (1) fields directly engaged in the efferent control of peripheral muscle contraction, (2) fields engaged in preparatory activity for reaching, and (3) fields appearing after learning of the task has taken place. PMID- 8207467 TI - Regulation of M current by intracellular calcium in bullfrog sympathetic ganglion neurons. AB - Regulation of M current (lM) by intracellular free calcium was studied in dissociated bullfrog sympathetic ganglion B cells using whole-cell recording, intracellular perfusion, and confocal calcium imaging. BAPTA (20 mM) and appropriate amounts of calcium were added to pipette solutions to clamp calcium at different levels. A high concentration of BAPTA itself mildly inhibited lM. Intracellular perfusion effectively controlled cellular free calcium; this was confirmed by confocal imaging with the calcium indicator fluo-3. In a calcium free environment (no calcium added to either side of the cell membrane), average lM was 166 pA. Raising intracellular free calcium to 60 nM or higher reversibly enhanced lM by more than 100%. The maximum M conductance doubled upon raising calcium from 0 to 120 nM, and was accompanied by a -11 mV shift of the half activation voltage. The kinetics of the closing and reopening relaxations of lM were also altered by raising calcium. Enhancement of lM by calcium required ATP in the pipette. TEA (5 mM) and d-tubocurarine (d-TC; 100 microM) did not alter the calcium effect, indicating that it was the M current being modulated and not other K+ currents. High calcium (450 nM) reduced lM. The up- and downregulation of lM paralleled the increases and decreases of fluorescence intensity observed via calcium imaging. Changing extracellular calcium had no significant effect on lM or cellular fluorescence. The role of calcium in muscarinic and peptidergic modulation of lM was also explored. Muscarine (1 or 10 microM) inhibited lM less at zero calcium than at higher calcium. Nearly complete suppression occurred with 120 nM calcium in the presence of 20 mM BAPTA. lM overrecovered upon washout of muscarine at 120 nM calcium, while little overrecovery of lM developed at zero calcium. Similar effects were observed at zero and 120 nM calcium when using the peptide LHRH to inhibit lM. We conclude that the absolute level of free calcium determines the size of lM, and that a minimum sustained level of calcium is required both for optimal suppression of lM by muscarine and for overrecovery. While our data suggest that resting calcium levels play a permissive role in muscarinic suppression, an additional role for agonist-induced calcium increases cannot be ruled out. PMID- 8207468 TI - Thalamocortical axons extend along a chondroitin sulfate proteoglycan-enriched pathway coincident with the neocortical subplate and distinct from the efferent path. AB - The distinct axonal tracts of the mature nervous system are defined during development by sets of substrate-bound and diffusible molecular signals that promote or restrict axonal elongation. In the adult cerebral cortex, efferent and afferent axons are segregated within the white matter. To define the relationship of growing efferent and afferent axons in the developing murine cortex to chondroitin sulfate proteoglycans (CSPGs) in the pericellular and extracellular matrix, we used the fluorescent tracer Dil to determine axonal trajectories and immunolabeling to disclose the distribution of CSPGs. Axons of neurons in the preplate are the first to leave the cortex; they arise in the CSPG-rich preplate and extend obliquely across it to enter the CSPG-poor intermediate zone. Slightly later, axons of cortical plate neurons extend directly across the CSPG-rich subplate, and then turn abruptly to run in the upper intermediate zone. In contrast, once afferent axons from the thalamus reach the developing cortical wall, their intracortical trajectory is centered on the CSPG-rich subplate, above the path taken by efferent axons. Our findings demonstrate a molecular difference between the adjacent but distinct efferent and afferent pathways in developing neocortex. Early efferents cross the subplate and follow a pathway that contains very little CSPG, while afferents preferentially travel more superficially within the CSPG-rich subplate. Thus, CSPGs and associated extracellular matrix (ECM) components in the preplate/subplate do not form a barrier to axonal initiation or outgrowth in the neocortex as they may in other locations. Instead, their distribution suggests a role in defining discrete axonal pathways during early cortical development. PMID- 8207469 TI - Spatiotemporal structure of somatosensory responses of many-neuron ensembles in the rat ventral posterior medial nucleus of the thalamus. AB - Classically, the rat ventral posterior medial (VPM) nucleus of the thalamus has been considered as a simple passive relay for single-whisker information to the primary somatosensory cortex (SI). However, recent reports have suggested that the VPM could contain a much more coarsely coded and spatiotemporally complex representation of the rat whisker pad. To address this possibility properly, we have carried out chronic simultaneous recordings of large numbers (up to 23) of single neurons, distributed across the entire VPM, in both awake and lightly anesthetized adult rats. Quantitative, computer-based reconstruction of receptive fields (RFs) revealed that single VPM neurons exhibit significant responses to discrete stimulation of as many as 20 single whiskers (mean +/- SD RF size, 13.7 +/- 4.8 whiskers). By defining multiple response magnitude (RM) thresholds it was possible to subdivide these large VPM RFs quantitatively into a prominent center (mean +/- SD, 1.41 +/- 0.70 whiskers, RM > 95%) and an excitatory surround (up to 18 whiskers, RM < 95%). VPM neurons exhibited both short-latency responses (SLRs, from 4 to 10 msec poststimulus) and/or long-latency responses (LLRs, 15-25 msec), each followed by inhibitory responses. Though LLRs were weaker (mean +/- SD, 47.19 +/- 33.34 Hz) than SLRs (119.63 +/- 50.12 Hz), they often defined RFs that differed considerably from those defined by the SLRs of the same cell. In particular, VPM cells with short-latency RFs centered in caudal whiskers (e.g., C1, D1, E1) showed a poststimulus time-dependent shift of these RF centers toward the rostral whiskers (e.g., C4, D4, E4). These caudal-to-rostral (C-->RF shifts occurred in neurons with the largest RFs of our sample (17.2 +/- 2.4 whiskers). On the other hand, VPM cells with short-latency RFs centered in rostral whiskers had the smallest RFs (13.1 +/- 4.1 whiskers) and usually did not exhibit time dependent RF center shifts. Multivariate analysis revealed that these two groups of VPM neurons, C-->R shifting and rostral position (RP) cells, could be statistically distinguished according to a combination of three RF attributes (short-latency RF center location, RF size, and magnitude of RF center shift). Quantitative, computer-based reconstruction of "population response maps" demonstrated that the "place" coding for each single whisker in the VPM involved a distinct weighted contribution from a large proportion of the simultaneously recorded neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8207470 TI - VIP modulates neuronal nicotinic acetylcholine receptor function by a cyclic AMP dependent mechanism. AB - Neuronal nicotinic ACh receptors (AChRs) mediate synaptic transmission throughout the nervous system, and are regulated by cellular processes and interactions that include second messenger signaling pathways. In the case of chick ciliary ganglion neurons, activation of the cAMP-dependent signaling pathway with cAMP analogs enhances ACh sensitivity in a manner consistent with an increase in the number of functional nicotinic receptors. We have now identified vasoactive intestinal peptide (VIP) as a neuromodulator or "first messenger" in the cAMP mediated pathway that regulates neuronal AChRs. Using cAMP imaging and biochemical detection assays, we find that bath application of VIP elevates intracellular cAMP in freshly isolated ciliary ganglion neurons within minutes. The VIP treatment also enhances neuronal ACh sensitivity assessed with whole-cell recording. The enhanced ACh sensitivity produced by VIP appears with a short latency, similar to that associated with the increase in cAMP, and is not additive with the enhanced ACh sensitivity produced by bath application of a cAMP analog. In contrast, calcitonin gene-related peptide (CGRP), known to regulate muscle nicotinic AChRs via a cAMP-dependent pathway, has no detectable effect on levels of either cAMP or ACh sensitivity in the neurons. The results indicate that VIP enhances the ACh sensitivity of ciliary ganglion neurons via a cAMP dependent signaling pathway, presumably by interaction with a specific receptor. Since VIP-like immunoreactivity is present in the presynaptic nerve terminals of avian ciliary ganglia, a VIP-like peptide could modulate AChRs in vivo. PMID- 8207471 TI - Spinal cord neuroblasts proliferate in response to basic fibroblast growth factor. AB - Trophic factors may function as one of the epigenic signals responsible for the proliferation, growth, migration, and differentiation of neurons and glia during embryogenesis. The present study reports that basic fibroblast growth factor (bFGF) at high concentrations (10-100 ng/ml) is a mitogen for embryonic spinal cord cells that have already committed to a neuronal pathway and are expressing neuronal phenotypes (neuroblasts). Neuroblasts proliferate with a doubling time of 2.5 d. To characterize the nature of cells proliferating in response to bFGF, we have established long-term cultures of neuroblasts that can be passaged, freeze thawed, and recultured. In cultures the proportion of astrocytes remained the same, indicating limited survival and proliferation of these cells in response to bFGF. These results indicate that bFGF has mitogenic effects preferably on neuroblasts. The morphological and biochemical characterizations of the neuronal populations present in the long-term neuroblast cultures are presented here. The presence of cholinergic and GABAergic neurons in the cultures was established by immunocytochemical analysis. The cultures contain a small number of motoneurons as judged by their immunostaining with ChAT, low-affinity NGF receptor (LNGFR), and large size. Among all other growth factors tested for their mitogenic effects on embryonic spinal cord cells in culture, only epidermal growth factor (EGF) showed such effects, but to a lesser degree. The proliferative nature of neuroblasts has made it possible to transduce the Escherichia coli beta-galactosidase (LacZ) gene stably into these cells in vitro using a retroviral vector. The transfected cells expressing the foreign gene can be passaged, freeze thawed, and recultured without the loss of transgenes. The ability to transduce foreign genes stably into these cells permits implantation of these cells in the spinal cord to study cellular and biochemical behaviors and gene expression in defined neuronal populations in in vivo environments. PMID- 8207472 TI - Identification and characterization of pleural neurons that inhibit tail sensory neurons and motor neurons in Aplysia: correlation with FMRFamide immunoreactivity. AB - Neurons on the rostral edge of the ventral surface of the right pleural ganglion were identified as elements of the circuit mediating the defensive tail withdrawal reflex of Aplysia. These neurons produced IPSPs in tail sensory neurons and were classified into two groups, RPI4 and RPI5, according to their affinity for an antibody directed against FMRFamide. RPI4 was not FMRFamide immunoreactive, and RPI5 was. RPI4 and RPI5 were found to have different electrophysiological profiles. The summated IPSPs in sensory neurons produced by RPI4 developed more rapidly and had a shorter duration than those produced by RPI5. In addition, RPI4 produced IPSPs in the tail motor neurons, whereas RPI5 did not. Both RPI4 and RPI5 received excitatory synaptic inputs from stimulation of the pleural-abdominal connective as well as peripheral nerves P8 and P9, which innervate the tail and posterior part of the animal's body. These inputs were sufficient to elicit spikes. In RPI4, the excitatory synaptic inputs were followed by short and transient hyperpolarization, whereas in RPI5, the excitatory synaptic inputs were followed by slow and long-lasting hyperpolarization. Excitatory inputs elicited in RPI4 by stimulation of peripheral nerves appeared to be mediated, at least in part, by activation of tail sensory neurons. Intracellular stimulation of sensory neurons produced EPSPs in RPI4 that appeared to be monosynaptic. These results suggest that inhibitory interneurons underlying the circuit of the tail withdrawal reflex may play roles in mediating or modulating neuronal responses to tail stimulation. By inhibiting tail sensory and motor neurons, these interneurons may reduce the effectiveness of an animal's response to stimulation of the tail. PMID- 8207473 TI - Local modulation of basal forebrain: effects on working and reference memory. AB - The functional roles of the medial septal area (MSA) and nucleus basalis magnocellularis (NBM) in memory were investigated to determine (1) their relative contribution to working and reference memory, (2) their operation in spatial and nonspatial memory, (3) the temporal dynamics of the neural activity within these nuclei as they relate to mnemonic processes, (4) the neurochemical regulation of their activity, and (5) the importance of ACh for their function. Working memory was tested in a continuous conditional discrimination (CCD), and reference memory was tested in the CCD and a sensory discrimination (SD). Bipolar recording electrodes in the dentate hilus monitored hippocampal EEG (theta rhythm). Immediately prior to behavioral testing, trained rats were infused with tetracaine, scopolamine, or muscimol into the MSA or NBM, and the subsequent behavioral and physiological changes were measured and correlated. MSA infusions of all three drugs reduced the power of hippocampal theta and impaired choice accuracy in the CCD; the magnitude of both effects was greater for larger doses and steadily decreased over time after the infusion, producing a strong positive correlation between the power of theta and choice accuracy in the CCD. These infusions had no effect on measures of reference memory in the CCD or in the SD. The results demonstrate that rhythmic activity along the septohippocampal pathway reflects processing of nonspatial working, but not reference memory. NBM infusions did not affect hippocampal theta but did reduce choice accuracy in the SD and completely disrupted performance in the CCD. The NBM appears to have a critical role in both working and reference memory. PMID- 8207474 TI - Independent control of dendritic and axonal form in the developing lateral geniculate nucleus. AB - To identify mechanisms that regulate neuronal form in the mammalian CNS, we have examined dendritic development in the lateral geniculate nucleus (LGN) during the period of segregation of retinal ganglion cell axons. The tracer Dil was used to label retrogradely LGN neurons that send their axons to primary visual cortex at different ages between embryonic day 36 (E36) and E60 in the cat. LGN neurons grow extensively during this period, in concert with the progressive restriction of ganglion cell axons from the two eyes to their appropriate eye-specific layers. At E36 neurons have simple bipolar morphology; by E60 all have acquired complex multipolar dendritic trees. During this period, soma size increases by 190% and total dendritic length increases 240%. Dendritic complexity, as measured by dendritic branch points, also increases. As dendrites grow, the number of spines increases, but their density remains constant at 0.015/micron throughout this period. Since it is known that blockade of action potential activity significantly alters the branching pattern and extent of retinal ganglion cell axonal arbors within the LGN, we also investigated whether the dendritic development of the postsynaptic LGN neurons is similarly susceptible. Following 2 weeks of the intracranial minipump infusion of TTX between E42 and E56, the morphology of LGN neurons was examined. Surprisingly in view of the striking effect of the treatment on the morphology of retinal ganglion cell axons, dendritic growth and development were essentially normal. However, the density of dendritic spines increased almost threefold, suggesting that this specific feature of dendritic morphology is highly regulated by action potential activity. These observations indicate that normally during this period of development, the previously described changes that occur in the morphology of the presynaptic inputs to LGN neurons are accompanied by a progressive growth of post-synaptic dendrites. Because the intracranial TTX infusions have almost certainly blocked all sodium action potentials, our results suggest that the basic dendritic framework of LGN neurons can be achieved even in the absence of this form of neural activity. Moreover, since the same treatment causes a profound change in the morphology of the presynaptic axons, at least some aspects of axonal and dendritic form must be controlled independently during this prenatal period of development. PMID- 8207475 TI - Distribution and synaptic localization of immunocytochemically identified NMDA receptor subunit proteins in sensory-motor and visual cortices of monkey and human. AB - NMDA receptors are composed of multiple receptor subunit proteins, of which NMDAR1 appears to be a critical component for normal receptor function (Nakanishi, 1992). In this study, quantitative immunocytochemical methods were used at the light and electron microscopic levels to localize NMDAR1 subunits in the primary motor (M1) and somatic sensory (S1) cortex of monkeys, and in the primary visual cortices (V1) of monkey and human. Three principal features of NMDAR1 subunit organization were examined in detail in the monkey cortex: (1) the laminar and cellular distribution patterns, relying in part on double-labeling paradigms with the calcium-binding proteins parvalbumin (PV) and calretinin (CR) as markers for discrete subpopulations of GABAergic interneurons; (2) the codistribution of NMDAR1 subunits with non-NMDA ionotropic receptor subunits; (3) a quantitative assessment of the percentages of asymmetrical synapses in layers II/III, IV, and V/VI that were NMDAR1 immunoreactive. In monkey M1, S1, and V1, NMDAR 1 immunoreactivity was present in all layers, localized primarily to large numbers of pyramidal cell somata and proximal apical dendrites, to presumptive spiny stellate cells in layer IV of V1, and to the vast majority (approximately 80-90%) of PV-immunoreactive cells. By contrast, NMDAR1 immunoreactivity was present in only a very small percentage of the CR-immunoreactive cells (approximately 6-9%). Colocalization with non-NMDA receptor subunits showed that all cells (100%) that contained GluR2/3 subunits were also NMDAR1 immunoreactive. In addition, the complete codistribution of GluR5/6/7 subunits with GluR2/3 subunits suggests, indirectly, that all GluR5/6/7-immunoreactive cells are also NMDAR1 immunoreactive. The laminar and cellular distribution patterns of immunostaining in human V1 were very similar to those in monkey V1. Electron microscopy of monkey sections confirmed an extensive dendritic and synaptic localization of NMDAR1 subunits. Labeling of synapses was present on asymmetrical postsynaptic densities associated with both dendritic shafts and spines. In supragranular layers of V1, a greater percentage of asymmetrical synapses were NMDAR1 immunopositive (44%) in comparison to layer IVC beta (34%) or deep layers (19%). In contrast, in area 3b of S1, the percentage of labeled synapses was greatest in layer IV (45%) in comparison to superficial (26%) and deep (37%) layers, while in M1, the percentages of labeled synapses were similar between superficial (46%) and deep (40%) layers. Taken together, these data indicate that NMDAR1-immunoreactive cells in neocortex represent a morphologically, functionally, and neurochemically heterogeneous population.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8207476 TI - Androgenic regulation of tubulin gene expression in axotomized hamster facial motoneurons. AB - We have previously demonstrated that systemic administration of testosterone increases the rate of axonal regeneration following facial nerve crush in adult male hamsters. In this investigation, the molecular mechanisms by which androgens may enhance axonal regeneration were examined. Specifically, the following question was addressed using Northern blot and in situ hybridization with three cytoskeletal cDNA probes complementary to beta II-, beta III-, and alpha 1 tubulin mRNA: does exogenous testosterone augment axotomy-induced changes in tubulin mRNA expression in hamster facial motoneurons (FMN)? Adult male hamsters were subjected to unilateral facial nerve severance, with the opposite side serving as an internal control. One-half of the animals were subcutaneously implanted with Silastic capsules containing crystalline testosterone propionate and the other half implanted with blank capsules. Postoperative survival times were 2 and 7 d. At 2 d after axotomy alone, no changes in levels of any of the three tubulin mRNAs were observed in the injured FMN. However, by 7 d after axotomy, significant increases in all three tubulin mRNAs were observed. This time course of axotomy-induced changes in tubulin gene expression is consistent with findings in other injured neuronal populations. Administration of testosterone at the time of injury had two major effects on the cytoskeletal response pattern in axotomized FMN. First, testosterone differentially regulated the set of tubulin mRNAs examined, in that beta II-tubulin mRNA levels were selectively altered by the steroid, whereas beta III- or alpha 1-tubulin mRNAs were not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207477 TI - Adenosine acting at an A1 receptor decreases N-type calcium current in mouse motoneurons. AB - The neuromodulator adenosine is known to decrease neurotransmitter release at the neuromuscular junction by activation of an A1 adenosine receptor coupled to a pertussis toxin-sensitive G protein. Among the mechanisms that could contribute to the depression of neurotransmitter release is reduced entry of calcium through channels located in the presynaptic terminal. In the present study, we have examined the effects of adenosine on high-voltage-activated (HVA) calcium currents in motoneurons, the presynaptic cells of the neuromuscular junction. The motoneurons were isolated from embryonic mice, placed in primary tissue culture for 16 hr, and analyzed by means of the whole-cell patch-clamp technique. Adenosine (40 microM) reduced both transient and sustained components of HVA calcium current. This effect was blocked by the A1 antagonist 8 cyclopentyltheophylline (CPT; 100 nM) and was mimicked by the A1 agonist N6 cyclohexyladenosine (CHA; 50 nM to 10 microM) but not by the A2a agonist 2-p-(2 carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine (CGS-21680; 1 micron). Pretreatment with pertussis toxin (200 ng/ml, > 16 hr) abolished the depression of HVA calcium current by adenosine receptor activation. Brief (3 min) exposure of the cells to 10 microM omega-conotoxin GVIA irreversibly blocked a part of the HVA current, which can therefore be attributed to N-type channels; the remaining current was unaffected by adenosine receptor activation. Hence, it appears that adenosine decreases only the N-current portion of HVA current and that this inhibition occurs via an A1 receptor linked to a pertussis toxin sensitive G protein. Other investigators have shown that N-type channels do not play a primary role in eliciting transmitter release at the mammalian neuromuscular junction. Thus, it is uncertain what motoneuronal functions are influenced by adenosine modulation of N-type channels. PMID- 8207478 TI - Serotonin modulates photic responses in the hamster suprachiasmatic nuclei. AB - The aim of the present study was to examine the effects of serotonin agonists on three elements of the photic response in the hamster suprachiasmatic nuclei (SCN). Both serotonin and the selective 5-HT1A agonist 8-OH-DPAT inhibited field potentials recorded in the SCN in response to optic nerve stimulation in the hypothalamic slice preparation. The effects of both drugs were dose related over a concentration range of 1-50 microM, and, in both cases, a maximal inhibition of approximately 60% was achieved at a concentration of 25-50 microM. Systemic administration of 8-OH-DPAT inhibited light-stimulated Fos expression in the SCN. A regionally selective pattern of inhibition was observed, with decreases restricted predominately to the ventral and dorsal borders of the SCN. Finally, systemic administration of 8-OH-DPAT was found to dose-dependently attenuate light-induced phase shifts of the free-running activity rhythm. The effects of 8 OH-DPAT on light-induced phase advances were dose dependent. Injection of 8-OH DPAT at a dose of 0.5 mg/kg caused 57% inhibition of light-induced phase advances, while a dose of 5 mg/kg inhibited the phase advance by 82%. Injection of 0.05 mg/kg 8-OH-DPAT did not significantly inhibit light-induced phase advances. Injection of 5 mg/kg 8-OH-DPAT alone did not significantly alter the phase of the activity rhythm. Similarly, injection of 5 mg/kg 8-OH-DPAT 30 min prior to light stimulation at CT14 completely inhibited light-induced phase delays, while this dose of the drug did not alter the phase of the activity rhythm when administered alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207479 TI - c-fos expression in vomeronasal pathways of mated or pheromone-stimulated male golden hamsters: contributions from vomeronasal sensory input and expression related to mating performance. AB - The vomeronasal system projects to the accessory olfactory bulb (AOB), to the medial (Me) and posterior medial cortical nuclei (PMCN) of the amygdala, to the bed nucleus of the stria terminalis (BNST), and to other central structures shown to be important in mating behavior, including the medial preoptic area (MPOA). In these experiments c-fos expression was used as a marker of neural activity to identify the contribution of vomeronasal sensory input during mating behavior in male golden hamsters, either intact or with vomeronasal organs removed (VNX). Inexperienced hamsters were either stimulated with a receptive female and allowed to mate, exposed to female hamster vaginal fluid (HVF), which contains stimuli known to act through the VN system, or placed in a clean cage alone. Densely stained Fos-positive nuclei were evident in mated animals in the central VN pathway [AOB, Me, posterior medial BNST (pmBNST)] and a VN target area (MPOA). HVF-exposed animals showed Fos expression in the AOB, Me, and BNST but not MPOA. Unstimulated animals showed almost no activation. Most VNX animals exposed to females did not mate, but performed intense chemoinvestigation. They had few Fos positive nuclei in any of these areas except the caudal pmBNST. A few VNX animals that did mate had patterns of Fos activation that were similar but less intense than those of intact mating animals, suggesting a selective activation of VN central pathways during mating regardless of VN sensory input. The main olfactory system showed low levels of Fos expression in all animals (stimulated and unstimulated). Fos expression in the MPOA and rostral pmBNST was seen only in mated animals, suggesting that these regions are concerned with mating performance or its consequences, rather than the chemosensory input that triggers it. Fos expression in the caudal encapsulated pmBNST was evident in all groups of animals that performed chemosensory investigation, regardless of VN status or mating, suggesting that this region either directs or responds to chemosensory investigation. PMID- 8207480 TI - Central sprouting and functional plasticity of regenerated primary afferents. AB - A combination of neuroanatomical and electrophysiological techniques was used to study the effects of peripheral axotomy and regeneration of primary afferents on their central projections in the spinal cord. Individual regenerated afferent fibers were impaled with HRP-filled electrodes in the dorsal columns of alpha chloralose-anesthetized cats and activated by current pulses delivered via the intracellular electrode. The resulting cord dorsum potentials (CDPs) were recorded at four rostrocaudal locations and HRP was iontophoretically injected into the fiber. Central distributions of boutons and CDPs were compared with peripheral receptor type to determine the accuracy of peripheral regeneration and the effects of central-peripheral mismatches. Reconstruction of the central projections of 13 individual afferents for which the adequate stimulus and CDPs had been recorded revealed many abnormalities. For example, unlike controls, four group I and II afferents with central projections typical of proprioceptors (concentrated in laminae V, VI, and VII) innervating either cutaneous or noncutaneous targets evoked measurable CDPs. Three other group II or A beta afferents innervating low-threshold mechanoreceptors with central terminations confined to the dorsal horn exhibited extensive collateralization in laminae I and II in addition to large numbers of terminals in laminae III-IV. These fibers activated central networks whose adaptation behavior was identical to those evoked by high-threshold mechanoreceptive afferents in controls. These results suggest that primary afferents and their central connections are capable of significant modifications following axotomy and regeneration. In addition, the anatomical studies indicate some reorganization in the laminar distribution of boutons as well as in bouton size. PMID- 8207481 TI - Injury-induced plasticity of spinal reflex activity: NK1 neurokinin receptor activation and enhanced A- and C-fiber mediated responses in the rat spinal cord in vitro. AB - A- and C-fiber evoked ventral root potential (VRP) responses have been examined in isolated spinal cord preparations maintained in vitro that were taken from young rats in which behavioral hyperalgesia (thermal and mechanical) was induced following UV irradiation of one hindpaw. Evoked VRPs were compared with those in naive untreated animals. The duration of both the A- and C-fiber evoked VRP was significantly increased in UV-treated animals. The amplitude of the summated VRP evoked by repeated low-frequency (1.0-5.0 Hz) C-fiber stimulation, a measure of windup, was significantly greater in UV-treated animals. In UV-treated animals, repeated low-frequency (1.0-5.0 Hz) stimulation of A-fiber inputs to the spinal cord also evoked a significant summated VRP, which was not observed in spinal cords from untreated animals. In naive animals the prolonged VRP evoked following single shock C-fiber stimulation was significantly antagonized by the NMDA receptor antagonist D-AP5 and the NK2 receptor antagonist MEN, 10376 but not by the NK1 receptor antagonists CP-96,345 or RP,67580. Summated VRPs evoked by repeated C-fiber stimulation in naive animals were significantly antagonized only by D-AP5. In hyperalgesic animals the prolonged VRP evoked by C-fiber stimulation was significantly reduced by NK1, NK2, and NMDA antagonists. The summated VRP was also significantly reduced by these antagonists. In both untreated and UV irradiated animals the single shock evoked A-fiber ventral root response was significantly antagonized only by D-AP5. However, the summated VRP evoked by repeated A-fiber stimulation in UV-treated animals was also significantly reduced by NMDA, NK1, and NK2 receptor antagonists. The present study has demonstrated enhanced A- and C-fiber evoked responses in the rat spinal cord in vitro following induction of a peripheral injury by UV irradiation and which was associated with behavioral hyperalgesia to thermal and mechanical stimuli. Under this condition, repetitive stimulation of A-fiber primary afferents was capable of producing an enhancement of spinal excitability similar to that evoked by C fibers in normal animals. Furthermore, we have observed the expression of an NK1 receptor component to the C-fiber evoked response following the establishment of the peripheral injury. The enhanced ventral root responses and changes in receptor sensitivity may contribute to the phenomenon of central sensitization and may be directly related to the behavioral hyperalgesia observed. Moreover, these findings may be relevant to the mechanisms of enhanced central excitability that occur in clinical conditions of inflammatory hyperalgesia and neuropathic pain. PMID- 8207482 TI - Activity-induced changes in synaptic release sites at the crayfish neuromuscular junction. AB - Crustacean motor axons provide a model in which activity-dependent changes in synaptic physiology and synaptic structure can be concurrently observed in single identifiable neurons. In response to a train of stimulation, crustacean neuromuscular junctions undergo pronounced facilitation of transmitter release. The effects of maintained high-frequency stimulation may persist for at least several hours ("long-term facilitation"). Electrophysiological studies suggest that the number of "active" synapses contributing transmitter quanta at low frequencies of stimulation increases during and after a train of high-frequency stimulation. However, at different terminal recording sites the effect of stimulation varies, and it was observed that not all released quanta produce a voltage change in the postsynaptic muscle cell. Electron microscopic examinations of serial sections from nerve terminals subjected to stimulation were made to determine whether changes in synaptic structure could be correlated with activity induced long-lasting enhancement of transmission. A procedure was introduced for marking a recorded terminal with fluorescent polystyrene microspheres, which are visible in electron micrographs of the recording site. Crustacean nerve terminals possess a large number of discrete synapses, a small fraction of which have multiple presynaptic "active zones" (dense bodies with clustered synaptic vesicles, thought to represent sites of evoked transmitter release). In terminals previously stimulated, the proportion of synapses with multiple "active zones" is greater than in control unstimulated terminals. Total synaptic vesicle counts and readily releasable vesicles at synapses are not significantly different in previously stimulated terminals and controls. In terminals fixed during stimulation a few synapses show evidence of division in "active zones," and synaptic vesicle counts are lower than in controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207483 TI - Postsynaptic modulation of synaptic efficacy at mixed synapses on the Mauthner cell. AB - Extracellular application of dopamine in the synaptic bed of the lateral dendrite of the goldfish Mauthner (M-) cell enhances both the electrical and chemical components of the mixed excitatory postsynaptic potential (EPSP) evoked by ipsilateral eighth nerve stimulation (Pereda et. al., 1992). We describe here results of experiments designed to determine the locus of action of dopamine and the underlying cellular mechanisms. This amine acts independently on the two modes of transmission, since (1) the percentage increases in the two were not correlated, (2) the time courses of their modifications were independent, and (3) the observed increases in synaptic responses cannot be attributed to a generalized effect on M-cell input conductance, which was increased by dopamine, a change that would rather be expected to shunt the synaptic potentials. Also, dopamine does not produce presynaptic spike broadening and does not modify paired pulse facilitation, two indications that it acts postsynaptically. The alterations in the mixed EPSP are presumably due to activation of a postsynaptic cAMP-dependent phosphorylation pathway. Specifically, they did not occur if the cAMP-dependent protein kinase inhibitor PKI5-24 was injected intradendritically prior to dopamine application, and they could, on the other hand, be mimicked by injections of the catalytic subunit of the cAMP-dependent protein kinase, PKACAT. In contrast, neither manipulation altered the M-cell input conductance directly or affected the dopamine-induced increase in conductance, suggesting this effect of dopamine is cAMP independent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207484 TI - Neuronal expression of glypican, a cell-surface glycosylphosphatidylinositol anchored heparan sulfate proteoglycan, in the adult rat nervous system. AB - Cell-surface proteoglycans have been implicated in cell responses to growth factors, extracellular matrix, and cell adhesion molecules. M12, one of the most abundant membrane-associated proteoglycans in the adult rat brain, is a approximately 65 kDa glycosylphosphatidylinositol-linked protein that bears heparan sulfate chains (Herndon and Lander, 1990). To assess its identity, M12 was purified and internal peptide sequences obtained. Comparison of the results with protein sequence predicted by a cDNA cloned from PC12 cells indicated that M12 is rat glypican, a proteoglycan first cloned from human fibroblasts. In addition, antibodies raised against a rat glypican fusion protein specifically detected the 65 kDa brain proteoglycan core protein, both by immunoprecipitation and by Western blotting. Northern blot analysis using a rat glypican probe also detected glypican message in the adult, as well as the developing rat brain. In situ hybridization with glypican RNA probes showed that glypican is expressed in a subset of structures in the adult rat nervous system. These include the hippocampus, dorsal thalamus, amygdala, cerebral cortex, piriform cortex, olfactory tubercle, several cranial nerve nuclei, the ventral horn of the spinal cord, and the dorsal root ganglia. Several other brain regions exhibited little or no hybridization over background. In most cases where glypican hybridization was observed, the signal could be localized specifically to the cell bodies of identifiable neurons, for example, spinal motoneurons, hippocampal pyramidal cells. In the cerebral cortex, glypican hybridization was found in layers 2/3, 5, and 6, but was missing from 1 and 4. The data suggest that glypican is expressed primarily by subpopulations of projection neurons in the adult rat nervous system. PMID- 8207485 TI - Distribution of fos-like immunoreactivity in the medullary and upper cervical dorsal horn produced by stimulation of dural blood vessels in the rat. AB - Neurophysiological studies have generally failed to find evidence of a specific ascending pathway for visceral nociception. However, pain that arises from deep or visceral tissues typically differs from cutaneous pain, particularly in its diffuse, poorly localized quality. In this study, the c-fos mapping technique was used in order to investigate possible differences in the distribution of central neurons activated by afferent pathways from cutaneous and deep tissues that may be related to the differing quality of the sensations they evoke. The distribution of neurons in the upper cervical and medullary dorsal horn that displayed fos-like immunoreactivity (fos-LI) was examined following mechanical stimulation of dural blood vessels (transverse and superior sagittal sinuses), and was compared to that found following mechanical, thermal, and chemical stimulation of facial sites. Dural stimulation was carried out Brevital anesthesia in rats that had received a chronic surgical exposure of the transverse and superior sagittal sinuses 2 d earlier. Localized mechanical stimulation of the dural surface of the transverse sinus produced a predominantly ipsilateral increase in the number of fos-LI neurons in the medullary and upper cervical dorsal horn (primarily laminae I and V), and in the transition region between the trigeminal nucleus caudalis and interpolaris. Stimulation of the superior sagittal sinus produced increases in fos-LI labeling that were generally smaller than those produced by transverse sinus stimulation. The distribution of fos-LI labeling in the dorsal horn induced by dural stimulation differed from that induced by facial stimulation in two ways. (1) Dural stimulation produced a more diffuse distribution of fos-LI than facial stimulation in the dorsal horn. Whereas facial stimulation produced a dense, localized zone of fos-LI labeling in the dorsal horn, dural stimulation produced fos-LI labeling that extended from the midlevel of caudalis to C2/C3, and also extended across a large portion of the ventrolateral-to-dorsomedial axis of the dorsal horn. This distribution roughly corresponds to the representation of most of the dorsal half of the head and face. (2) Dural stimulation produced a more restricted laminar distribution of fos-LI labeling than facial stimulation, in that the dural-induced labeling in the superficial dorsal horn was primarily restricted to lamina I, whereas facial stimulation typically induced substantial labeling in both lamina I and the outer part of lamina II. These differences in the central organization of the afferent pathways from dural and facial sites may contribute to the differences in the quality of sensations evoked by these pathways. PMID- 8207486 TI - The effects of hippocampal formation ablation or fimbria-fornix section on performance of a nonspatial radial arm maze task by rats. AB - Rats with fimbria-fornix section or complete hippocampal aspiration lesions were postoperatively compared to unoperated controls in a nonspatial working memory task using an enclosed plus maze. Initial training (stage 1) was on a continuous two-choice nonmatching to sample task, using pseudo-trial-unique stimuli. Subsequent testing (stages 2-4) always had four boxes available at each choice opportunity, with each goal arm containing a distinctive goalbox. The positions of these boxes were interchanged between choice opportunities, so as to ensure that their relative positions were variable. Extramaze cues were as far as possible excluded. Choices of goalboxes that had not yet been visited within each test session were rewarded. In stage 2, the goalboxes were complex in design, and rats with lesions chose as accurately as controls. In stage 3, within-session interference effects were demonstrated, but these effects were not exacerbated by the lesions. Stage 4 demonstrated that when goalboxes that were simple in design were used the rats in both lesion groups showed a substantial impairment of choice accuracy, even though choice accuracy using complex goalboxes remained unimpaired. This extended previous work demonstrating that hippocampal dysfunction can be associated with nonspatial working memory impairments when large boxes differing in surface texture and appearance are used as stimuli, even though no such impairments are seen when smaller boxes containing complex objects are used. Further experiments will be needed to establish the critical features underlying these nonspatial working memory deficits. PMID- 8207487 TI - Motor sequence learning: a study with positron emission tomography. AB - We have used positron emission tomography to study the functional anatomy of motor sequence learning. Subjects learned sequences of keypresses by trial and error using auditory feedback. They were scanned with eyes closed under three conditions: at rest, while performing a sequence that was practiced before scanning until overlearned, and while learning new sequences at the same rate of performance. Compared with rest, both sequence tasks activated the contralateral sensorimotor cortex to the same extent. Comparing new learning with performance of the prelearned sequence, differences in activation were identified in other areas. (1) Prefrontal cortex was only activated during new sequence learning. (2) Lateral premotor cortex was significantly more activated during new learning, whereas the supplementary motor area was more activated during performance of the prelearned sequence. (3) Activation of parietal association cortex was present during both motor tasks, but was significantly greater during new learning. (4) The putamen was equally activated by both conditions. (5) The cerebellum was activated by both conditions, but the activation was more extensive and greater in degree during new learning. There was an extensive decrease in the activity of prestriate cortex, inferotemporal cortex, and the hippocampus in both active conditions, when compared with rest. These decreases were significantly greater during new learning. We draw three main conclusions. (1) The cerebellum is involved in the process by which motor tasks become automatic, whereas the putamen is equally activated by sequence learning and retrieval, and may play a similar role in both. (2) When subjects learn new sequences of motor actions, prefrontal cortex is activated. This may reflect the need to generate new responses. (3) Reduced activity of areas concerned with visual processing, particularly during new learning, suggests that selective attention may involve depressing the activity of cells in modalities that are not engaged by the task. PMID- 8207488 TI - Bidirectional synaptic transmission in Necturus taste buds. AB - Pairs of taste cells were impaled with intracellular recording microelectrodes in intact taste buds in slices of Necturus lingual epithelium. Applying short pulses of 140 mM KCl or 200 mM CaCl2 solutions to the apical pore elicited receptor potentials in taste receptor cells. Chemostimulation of receptor cells elicited postsynaptic responses in basal cells in the taste bud. Postsynaptic responses in basal cells had a threshold for activation and did not saturate with increasing doses of chemical stimulus applied to the receptor cells. We directly depolarized individual receptor cells and tested whether this would evoke postsynaptic responses in basal cells. Depolarizing receptor cells to approximately 0 mV evoked small depolarizing responses in basal cells in 16% of the experiments. The properties of these responses were consistent with their being mediated by a chemical synapse. A comparison of the responses in basal cells evoked by depolarizing single receptor cells, with responses evoked by stimulating the entire receptor cell population with KCl suggests that there is extensive synaptic convergence from receptor cells onto each basal cell. We also tested whether electrical excitation of basal cells would elicit (retrograde) synaptic responses in receptor cells. Single depolarizing pulses (up to 1 sec duration) applied to basal cells through the intracellular recording microelectrode never evoked synaptic responses in receptor cells. However, when repetitive electrical stimuli were applied to basal cells (four to six 1 sec depolarizations to approximately 0 mV every 12 sec) we observed prolonged effects on receptor cells in 11 of 23 experiments. These effects included an increase in the amplitude of receptor potentials elicited by KCI (mean +/- SD = +19 +/- 5%), an increase in membrane input resistance of receptor cells (+27 +/- 11%), and a hyperpolarization of receptor cells (3-10 mV). In control experiments, repetitive stimulation of one receptor cell never elicited such effects in another receptor cell. We investigated the possibility that serotonin (5-HT), released from basal cells, mediated the above modulatory effects on receptor cells. Bath-applied 5-HT (100 microM) mimicked the effects produced by repetitive basal cell stimulation (KCI responses increased by 23 +/- 12%; input resistance increased by 24 +/- 11%; hyperpolarization of 5-15 mV; N = 14). We conclude that basal cells release 5-HT onto adjacent taste receptor cells and that this enhances the electrotonic propagation of receptor potentials from the apical (chemosensitive) tip to the basal (synaptic) processes of receptor cells. The net effect is that activation of basal cells effectively increases the chemosensitivity of taste receptor cells. PMID- 8207489 TI - Neuronal coupling in the developing mammalian retina. AB - During the first 3 weeks of postnatal development in the ferret retina, cells in the ganglion cell layer spontaneously generate waves of electrical activity that travel across the retina in the absence of mature photoreceptors (Meister et al., 1991; Wong et al., 1993). Since few chemical synapses are present at the earliest stages when waves are present, we have explored whether gap junctions could act to correlate the activity of cells in the immature ganglion cell layer. Retinal ganglion cells in a living in vitro preparation from postnatal day 1 (P1) to P45 were intracellularly injected with the tracer Neurobiotin and the fluorescent dye Lucifer yellow, molecules that are known to pass through gap junctions. Lucifer yellow consistently filled only the injected cell, whereas Neurobiotin filled not only the injected cell but also passed to a constellation of neighboring cells. Coupling revealed by Neurobiotin is seen as early as P1, but, at this stage, it was not possible to identify the various morphological types of cells that were coupled. Thereafter, alpha ganglion cells showed homologous coupling to other alpha cells and to both conventionally placed and displaced amacrine cells. Likewise, gamma ganglion cells appeared coupled to other gamma cells and to amacrine cells. However, beta ganglion cells never showed tracer coupling in the neonatal or in adult retinas. The percentage of alpha and gamma cells that were coupled to other cells increased progressively with age. By the end of the third postnatal week, the pattern of Neurobiotin coupling in the ferret retina was adult-like, with virtually every injected alpha cell showing tracer coupling. Our observations suggest that intercellular junctions able to pass Neurobiotin are present in the inner plexiform layer during the period when the firing of retinal ganglion cells is highly correlated. Such junctions could contribute to synchronization of the activity of subsets of neighboring ganglion cells during development, but it cannot be the sole mediator of this activity because beta cells, which also participate in the correlated activity, showed no coupling at any stage. In addition, the continued presence of coupling in the adult retina implies that other changes in retinal circuitry are likely to contribute to the disappearance of the waves. PMID- 8207490 TI - Developmental regulation of the hypothalamic metabotropic glutamate receptor mGluR1. AB - The expression of the metabotropic glutamate receptor mGluR1 was studied with Northern and Western blot analysis, with immunocytochemistry, and with Ca2+ digital imaging in the developing rat hypothalamus. mGluR1 is coupled to a G protein and activation by glutamate and related agonists leads to intracellular phosphotidylinositol hydrolysis and Ca2+ mobilization. mGluR1 RNA could be detected in embryonic hypothalamus, and by the day of birth and prior to the primary period of synaptogenesis, both mGluR1 RNA and protein were strongly expressed. In parallel experiments with digital imaging of cultured hypothalamic cells, some embryonic day 18 hypothalamic neurons and many astrocytes after 3 d in vitro showed Ca2+ responses to quisqualate and t-ACPD, and to glutamate in the absence of extracellular Ca2+. A greater number of embryonic neurons responded to NMDA than to agonists of the metabotropic receptor. With increased development time in culture, the number of neurons that responded to metabotropic glutamate receptor agonists increased. In the adult hypothalamus, mGluR1-immunoreactive neurons were widespread, and particularly dense in the dorsomedial, lateral, and anterior hypothalamus/preoptic areas, and in the mammillary body. Strongly immunoreactive cells were interspersed among neurons with no immunoreactivity. In developing neurons a diffuse immunostaining appeared along dendrites and somata. With time, beginning in the first week after birth, strongly stained puncta appeared, possibly associated with synaptic specializations. These puncta were numerous on dendrites of some adult neurons, and were the most strongly stained regions of neurons. Neurons developing in vitro at low neuron densities showed a development of mGluR1 immunoreactivity similar to that of neurons in vivo, but with a delayed progression of immunostaining. We found no obvious staining of axons or of astrocytes. A strong expression of mGluR1 protein was found in the hypothalamus during the first 2 postnatal weeks; this expression was partially reduced in adults. In contrast, cerebellum showed no reduction in mGluR1 protein in adults. Together these data suggest a complex regulation of mGluR1 during development, with sufficient expression of functional receptors in the developing hypothalamus to modulate morphogenesis and synaptogenesis, and later to play a role in transduction of glutamate signals in the adult. Different regions of the brain showed dramatic differences in the way each expresses mGluR1 during development. PMID- 8207491 TI - Terbium modulation of single gamma-aminobutyric acid-activated chloride channels in rat dorsal root ganglion neurons. AB - We have previously reported that lanthanides markedly potentiate the GABA-induced chloride current by acting at a distinct site on the GABAA receptor-channel complex (Ma and Narahashi, 1993a,b). These studies have now been extended to the single-channel level and changes in gating kinetics of GABAA receptor currents caused by 100 microM terbium (Tb3+) are reported. The GABA-induced currents were recorded from outside-out membrane patches isolated from rat dorsal root ganglion neurons in primary culture at a holding potential of -60 mV. At least two conductance levels were recorded, a main conductance of about 26 pS (70-80% of events) and a subconductance of about 19 pS (20-30% of events). These two conductances and the ratio of main- and subconductance state currents with respect to the number of events were not changed by Tb3+. The frequency of channel openings was also unchanged in the presence of Tb3+. The frequency histograms of open, close, and burst durations of the main-conductance state were best fitted by a sum of three exponential functions. All of the time constants remained unchanged by application of Tb3+ while the relative proportions of the longest open and burst duration time constants were increased and the relative proportion of longest closed time constant was decreased. We suggest that Tb3+ binds to an allosteric site on the GABAA receptor-channel complex to increase the apparent mean open time of the channel by increasing the affinity of GABA for the GABA binding site, and/or by shifting the distribution toward the open states so that the frequency of occurrence of longer open states is stabilized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207492 TI - mu-Opioid receptor-mediated reduction of neuronal calcium current occurs via a G(o)-type GTP-binding protein. AB - It has recently been shown that the activation of mu-opioid receptors inhibits several components of calcium channel current in rat DRG sensory neurons. mu Opioid receptors, acting through the pertussis toxin (PTX)-sensitive substrate Gi, also reduce the activity of neuronal adenylate cyclase, but the relationship of this effect to changes in calcium channel activity has yet to be determined. Using whole-cell recordings from acutely isolated rat DRG neurons, we examined the ability of the mu-opioid-selective agonist Tyr-Pro-NMe-Phe-D-Pro-NH2 (PLO17) to reduce calcium current after treatment with PTX and in the presence of the nonhydrolyzable GTP analog guanosine 5'-[-thio]triphosphate (GTP gamma S), to assess the role of G-proteins in the coupling of mu-opioid receptors to calcium channels. Inhibition of current by PLO17 was mimicked or rendered irreversible by intracellular administration of GTP gamma S, an activator of G-proteins, and was blocked by pretreatment of neurons with PTX. In contrast, when the catalytic subunit of cAMP-dependent protein kinase was included in the recording pipette, calcium currents increased in magnitude throughout the recording without attenuation of responses to PLO17. Thus, the mu-opioid-induced inhibition of calcium current occurs through activation of a Gi- or G(o)-type G-protein, but independent of changes in adenylate cyclase activity. As a first step in identifying this G-protein, we compared the ability of several antisera directed against specific regions of Gi and G(o)alpha subunits to block the inhibition in current by PLO17. Intracellular dialysis with an antiserum specific for G(o) (GC/2) attenuated calcium current inhibition by PLO17 in five of six neurons by an average of 75%. In contrast, there was no attenuation in the response to PLO17 when neurons were dialyzed with an anti-Gi1 alpha/Gi2 alpha antiserum (AS/7) or antibodies specific for alpha subunits of Gi proteins (Gi1/Gi2 or Gi3) in an identical manner. These results suggest that in rat DRG neurons mu-opioid receptors couple to calcium channels via the PTX-sensitive G(o) subclass of GTP binding proteins. PMID- 8207494 TI - Laminar selectivity of the cholinergic suppression of synaptic transmission in rat hippocampal region CA1: computational modeling and brain slice physiology. AB - ACh may set the dynamics of cortical function to those appropriate for learning new information. In models of the putative associative memory function of piriform cortex, selective suppression of intrinsic but not afferent fiber synaptic transmission by ACh prevents recall of previous input from interfering with the learning of new input (Hasselmo, 1993). Selective cholinergic suppression may play a similar role in the hippocampal formation, where Schaffer collateral synapses in stratum radiatum (s. rad) may store associations between activity in region CA3 and the entorhinal cortex input to region CA1 terminating in stratum lacunosum-moleculare (s. l-m). A computational model of region CA1 predicts that for effective associative memory function of the Schaffer collaterals, cholinergic suppression of synaptic transmission should be stronger in s. rad than in s. l-m. In the hippocampal slice preparation, we tested the effect of the cholinergic agonist carbachol (0.01-500 microM) on synaptic transmission in s. rad and s. l-m. Stimulating and recording electrodes were simultaneously placed in both layers, allowing analysis of the effect of carbachol on synaptic potentials in both layers during the same perfusion in each slice. Carbachol produced a significantly stronger suppression of stimulus-evoked EPSPs in s. rad than in s. l-m at all concentrations greater than 1 microM. At 100 microM, EPSP initial slopes were suppressed by 89.1 +/- 3.0% in s. rad, but only by 40.1 +/- 4.1% in s. l-m. The muscarinic antagonist atropine (1 microM) blocked cholinergic suppression in both layers. These data support the hypothesis that synaptic modification of the Schaffer collaterals may store associations between activity in region CA3 and the afferent input to region CA1 from the entorhinal cortex. In simulations, feedback regulation of cholinergic modulation based on activity in region CA1 sets the appropriate dynamics of learning for novel associations, and recall for familiar associations. PMID- 8207493 TI - Segregation of geniculocortical afferents during the critical period: a role for subplate neurons. AB - To investigate the cellular interactions within the mammalian visual cortex that are important in ocular dominance column formation, we have examined the role of subplate neurons in this process. LGN axons segregate in layer 4 of the cat's visual cortex between the third and sixth postnatal weeks to give rise to the adult pattern of ocular dominance columns. Subplate neurons are a transient population of neurons that sit in the white matter but have extensive projections into the overlying cortex, particularly layer 4, during neonatal life. Many subplate neurons are present at birth, but most are gone by the end of the period of LGN axon segregation. To examine whether these neurons are required for the segregation of LGN axons, we deleted them by intracortical injections of kainic acid either just after LGN axons had grown into layer 4 (first postnatal week) or later, just before the onset of segregation (third postnatal week). The consequences for the patterning of geniculocortical terminals were evaluated by transneuronal transport of 3H-proline injected into one eye at times when segregation would normally be complete. Following deletion of subplate neurons at either age, LGN axons failed to segregate into ocular dominance columns. Following the late deletions only, geniculocortical axons lost their laminar restriction to layer 4 and projected to layers 2 and 3 as well. Deletion of subplate neurons also resulted in long-term changes in the cytoarchitecture of layer 4. These observations suggest that the interactions that mediate segregation of LGN axons within layer 4 of visual cortex are susceptible to influences from subplate neurons. Although the mechanisms by which subplate neurons exert their effect are not yet clear, these experiments strongly suggest that interactions between LGN axons and layer 4 neurons are not sufficient for column formation, and that subplate neurons most likely play a critical role in interactions leading to ocular segregation. PMID- 8207495 TI - Retrograde transport of radiolabeled cytoskeletal proteins in transected nerves. AB - Slow axonal transport is the mechanism by which cytoskeletal proteins are distributed within the axon. This function has traditionally been considered an exclusively unidirectional, anterograde process. Previous observations of cytoskeletal redistribution in surviving, transected axons of the C57BL/Ola mouse led us to hypothesize a retrograde component of cytoskeletal transport. To test this hypothesis against previous methods of measuring slow transport of cytoskeleton, we radioactively pulse-labeled proteins in sensory neurons of C57BL/Ola mice and followed their redistribution by gel fluorography in ligated and unligated sciatic nerves. Slow axonal transport of cytoskeletal proteins proceeded with the same characteristics in C57BL/Ola as in standard C57BL/6 mice. In comparison to the transport profiles from unligated control nerves, in ligated nerves there was redistribution of radiolabeled neurofilament and tubulin proteins back toward the cell body during the 14 d experimental period. These observations demonstrate that pulse-labeled cytoskeletal proteins move bidirectionally in this experimental system, and may provide insight into the normal mechanisms of cytoskeletal maintenance. PMID- 8207496 TI - Comparison of mammalian adult and fetal nicotinic acetylcholine receptors stably expressed in fibroblasts. AB - Cells from a line of transformed quail fibroblasts (QT-6) were transfected with cDNAs coding for subunits of the mouse muscle nicotinic ACh receptor (AChR). Stable clones were selected that expressed subunits of the fetal-type AChR (alpha, beta, gamma, delta) or the adult-type AChR (alpha, beta, epsilon, delta). The receptors had the appropriate burst durations and single-channel conductances for the fetal or adult type, respectively. Each type of receptor had a dose response relationship that was close to a square law at low concentrations of ACh, implying that they contained two ACh-binding subunits. The metabolic stability of surface fetal and adult receptors was identical (about 10 hr half life), for two independent clones expressing fetal and two expressing adult AChR. The metabolic stability was unaffected by treatment with okadaic acid, which enhanced receptor phosphorylation. d-Tubocurarine (dTC) blocked both the binding of alpha-bungarotoxin (BTX) to the cells and the ACh-elicited current. dTC blocked BTX binding with indistinguishable efficacy for both fetal and adult AChR. However, it was sixfold less effective at blocking ACh-elicited current from fetal AChR. At least part of the difference results from the ability of fetal receptor channels to open when the receptor has one ACh and one dTC molecule bound, whereas channels of heteroliganded adult receptors do not open. The data indicate that the subunit composition directly affects physiological and pharmacological properties of muscle AChR, but has little effect by itself on metabolic stability. PMID- 8207497 TI - Immunolocalization of calpain I-mediated spectrin degradation to vulnerable neurons in the ischemic gerbil brain. AB - Transient ischemia-induced perturbations in calcium homeostasis have been proposed to lead to pathological activation of the cysteine protease calpain I and subsequent delayed neuronal death in the CA1 region of hippocampus. We report here on the design and characterization of antibodies selective for calpain generated fragments of brain spectrin, and their use for immunoblot and immunohistochemical analyses of calpain activation following cerebral ischemia in the gerbil. Although spectrin was susceptible to degradation in vitro by many mammalian proteases, only calpain degraded spectrin to generate fragments immunoreactive with the antibodies. Following 5 min of global ischemia, immunoreactivity for calpain-degraded spectrin was rapidly (within 30 min) and markedly elevated in the perikarya and dendrites of several populations of forebrain neurons. The rapid calpain activation was completely prevented by the NMDA receptor antagonist MK-801. At later times postischemia, but prior to frank neuronal necrosis, calpain-degraded spectrin was restricted to hippocampal area CA1 pyramidal neurons. Silver impregnation histochemistry confirmed that neuronal damage was confined to area CA1. The results indicate that while nonpathological NMDA receptor stimulation can activate calpain, only those neurons showing sustained calpain activation are destined to die. PMID- 8207498 TI - An in vitro model for the effects of estrogen on neurons employing estrogen receptor-transfected PC12 cells. AB - Estrogen alters neurite outgrowth, neuritic spine development, and synaptogenesis in estrogen-responsive areas of the rat brain. However, examination of the specific effects of estrogen on neurons in vivo has been difficult. An in vitro model for the effects of estrogen on neurons was developed, using the PC12 rat pheochromocytoma cell line. Wild-type cells (PC12-WT) were stably transfected either with an expression vector coding for the full-length cDNA for the human estrogen receptor (hER), or with a control vector. Resultant clones were isolated, screened for incorporation of vector and expression of ER mRNA and protein, and analyzed for morphologic responses to estrogen. PC12-WT, NEO9 (ER negative), and SER8 (ER-positive) cells exposed to 100 ng/ml NGF exhibited dose responsive neurite outgrowth within 2 d by light microscopy (LM). Coadministration of 10(-10) to 10(-9) M estradiol (E2) had minimal effects on neurite outgrowth, neuritic spine development, or interneuritic connections in NEO9 or PC12-WT cells, but in SER8 cells E2 led to additive and dose-dependent increases in neurite outgrowth, spine development, and interneuritic connectivity. Coincubation of SER8 cells with E2 and the antiestrogen ICI 164,384 negated estrogenic effects on spine development and interneuritic connectivity. At the electron microscopic (EM) level, intercellular abutments of NEO9 or PC12 WT cells contained few and rudimentary gap junctions, with no increase by E2. However, SER8 cells exhibited augmented basal frequencies of gap junctions that increased with E2 incubation. Microinjection of Lucifer yellow into PC12-WT and NEO9 cells demonstrated low frequencies of dye coupling and no change with E2, but SER8 cells demonstrated increased dye-coupling frequency with E2 coincubation. The results suggest that SER8 cells recapitulate estrogen effects on neurons in vivo. Estrogen appears to induce an inherent neural morphologic program in estrogen receptor (ER)-containing cells. These three cell lines provide a unique in vitro system for studying mechanisms of estrogen-neuron interactions. PMID- 8207499 TI - Some sensory neurons express neuropeptide Y receptors: potential paracrine inhibition of primary afferent nociceptors following peripheral nerve injury. AB - Neuropeptide Y (NPY) has been suggested to exert antinociceptive actions by inhibiting the release of neurotransmitters from trigeminal and dorsal root ganglia (DRG) neurons, but the site of direct NPY action in vivo and the NPY receptor subtype mediating these effects are unknown. 125I-peptide YY (PYY) was used to localize and characterize NPY receptor binding sites in trigeminal ganglia, DRG, and spinal cord of the rat, rabbit, and monkey. In the rat, rabbit, and monkey, 5-20% of trigeminal ganglia and DRG neurons express NPY binding sites. Unilateral cuff-induced neuropathy or transection of the rat sciatic nerve did not significantly alter the density or number of DRG neurons expressing NPY receptors. A unimodal size distribution for L4 and L5 DRG neurons expressing NPY binding sites in the rat was determined, with a mean cross-sectional area of 947 microns 2. In the spinal cord the highest concentration of NPY receptors is found in laminae I, II, V, X, and Onuf's nucleus. Pharmacological experiments using selective Y1 and Y2 receptor antagonists suggest that Y2 is the prominent NPY receptor subtype expressed in trigeminal ganglia neurons, DRG neurons, and spinal cord. Previous studies have demonstrated that a population of large-diameter, presumably myelinated primary afferents express NPY after peripheral nerve injury. NPY released from these injured large-diameter DRG neurons may act in a paracrine fashion to block the transmission of nociceptive information from the small- and medium-diameter DRG neurons that constitutively express NPY receptors. NPY receptors are therefore uniquely positioned to inhibit primary afferent nociceptors directly, especially after peripheral nerve injury. PMID- 8207500 TI - Responses of tonically active neurons in the primate's striatum undergo systematic changes during behavioral sensorimotor conditioning. AB - The basal ganglia have been implicated in motor planning and motor learning. In the study reported here, we directly tested for response plasticity in striatal neurons of macaque monkeys undergoing Pavlovian conditioning. To focus the study, we recorded from the tonically active neurons (TANs) of the striatum, which are known to respond to conditioned sensory stimuli that signal reward delivery and elicit behavioral reactions. The activities of 858 TANs were recorded extracellularly from the striatum in alert behaving macaque monkeys before, during, and after the acquisition of a classical conditioning task. Two monkeys were trained to lick reward juice delivered on a spoon simultaneously with the presentation of a click. Almost no licks were triggered by the cues at the start of training, but by the fifth day more than 90% of licks were triggered, and values were near 100% for the remainder of the 3 week training period. In the striatum, only a small number of TANs responded to the clicks at the start before conditioning (about 17%). During training, the numbers of responding TANs gradually increased, so that by the end of training more than 50-70% of the TANs recorded (51.3-73.5%) became responsive to the clicks. The responses consisted of a pause in firing that occurred approximately 90 msec after the click and that was in some cells preceded by a brief activation and in most cells was followed by a rebound excitation. Prolonged recordings from single TANs (n = 6) showed that individual TANs can acquire a conditioned response within at least as short a time as 10 min. TANs retained such responsiveness after overtraining, and also after a 4 week intermission in training. When the monkey was trained to receive rewards in relation to a new conditioning stimulus, TANs were capable of switching their sensory response to the new stimulus. Histological reconstruction showed that the TANs that became responsive were broadly distributed in the region of striatum explored, which included the dorsal half to two-thirds of the caudate nucleus and putamen over a large anteroposterior span. We conclude that, during the acquisition of a sensorimotor association, TANs widely distributed through the striatum become responsive to sensory stimuli that induce conditioned behavior. This distributed change in activity could serve to modulate the activity of surrounding projection neurons in the striatum engaged in mediating learned behavior. PMID- 8207501 TI - Pathogenic microbes of the oral environment. PMID- 8207502 TI - Periodontal profile of 15- to 19-year-old West Malaysian secondary school students. AB - A cross-sectional exploratory survey was conducted in six West Malaysian schools involving 762 fifteen- to eighteen-year-old secondary school students. Periodontal health status was assessed using the Community Periodontal Index of Treatment Needs (CPITN), utilizing six index teeth to represent the six sextants of the mouth. The results indicated that 66.8% of the students examined had healthy gingiva (Score 0), 2.6% had bleeding of the gingiva on gentle probing, while 30.6% had calculus on their teeth. In terms of treatment needs, 35.0% of those examined needed oral hygiene education, 34.4%, on the other hand, required scaling. No student was found to require complex treatment. Sex-specific comparison revealed a slightly higher prevalence of calculus formation in male students. In terms of race, the Malays had a higher prevalence of calculus formation than either Chinese or Indians. PMID- 8207503 TI - Study on the castability of Co-Cr alloy for cast plates. Part 4. Effects of sectional area, number of sprues and alloy components on castability. AB - Co-Cr alloy is used more frequently than Ni-Cr alloy as a nonprecious alloy for cast plates in Japan. Titanium with good biocompatibility has often been contained in the composition of this Co-Cr alloy. However, since the melting temperature of Co-Cr alloy is very high, about 1300 degrees C, and it oxidizes easily, a vacuum-pressure casting machine capable of melting this alloy in a reduced atmosphere has recently been developed. In this study, using the vacuum pressure casting machine, the possible effects of sectional area and the number of sprues attached to the cast plate wax pattern, as well as the alloy components, on the castability of three kinds of Co-Cr alloy containing titanium were examined. It was found that all of these parameters had significant effects on Co-Cr alloy castability. PMID- 8207504 TI - A study of temporomandibular joint sounds; Part 1. Relationship with articular disc displacements. AB - The relationship between complaints about temporomandibular joint (TMJ) sounds and the prevalence of disc displacements was studied. The rate of incidence of TMJ sounds was 42% in the 50 subjects investigated. In the subjects with TMJ sounds, 19% were diagnosed as having articular disc displacements. In the 58% sound-free subjects, 14% were found to have disc displacements. Therefore, it seems that patients with TMJ sounds do not always have disc displacements, and that a sound-free state does not necessarily indicate a healthy TMJ. PMID- 8207505 TI - Effect of pretreatment reagent for enamel on the adhesion of resin composite. AB - Aqueous solutions of methacryloyl tyrosine amide (MTYA), glyceryl methacrylate (GM), glutaraldehyde and succinic acid were prepared and their effectiveness as pretreatment reagents was evaluated by measuring the tensile bond strengths between resin composite and polished enamel. Pretreatment of polished enamel with MTYA.GM.S3 (A: 6% MTYA + 70% GM aqueous solution, B: 3% succinic acid aqueous solution) gave bond strengths of about 7 MPa, whereas pretreatment with MTYA.G.GM.S3 (A: 6% MTYA + 70% GM aqueous solution, B: 3% succinic acid + 2% glutaraldehyde aqueous solution) gave values of about 5 MPa. The mean bond strengths of each after 60 s of scrubbing with MTYA.GM.S3 or by MTYA.G.GM.S3 were raised to about 9.5 MPa, and the type of bond failure was fracture of the bonding agent. Although there were no resin tags, it was found that resin composite was able to adhere to polished enamel without acid etching. PMID- 8207506 TI - Three-dimensional measurement study of the maximum protuberance and cervical line of the upper molars. AB - The maximum protuberance and the cervical line of 48 upper first molars and 56 second molars were observed using a three-dimensional measuring device. On the basis of the results, the relationship between the maximum protuberance and the cervical line was investigated on the respective contour line and lateral aspect waveform. The contour of the cervical line was positioned at the center of the maximum protuberance in both first and second molars. The distance of the lateral aspect between the measurement points of the maximum protuberance and the cervical line were wider in the mesiodistal direction than in the buccolingual direction. In the second molar, the distance between the maximum protuberance and the cervical line was narrower, and the stricture from the tooth crown to the cervical line on the second molar was decreased. The lateral aspect waveform of the cervical line and maximum protuberance tended to be similar, but the top-to bottom distance of undulation on the maximum protuberance was longer than that of the cervical line. The buccolingual direction of the lateral aspect waveform showed much more marked fluctuations than that of the mesiodistal direction. PMID- 8207507 TI - Production and characterization of an anti-chicken transferrin. AB - Several lines of recent evidence have suggested that transferrin plays a significant role in tissue interaction or morphogenesis at early stages of embryo development. In the present study, an anti-chicken transferrin antibody was produced and its basic characteristics were clarified as a basis for use in further studies. An antiserum termed Toraji 3 was raised against chicken transferrin and purified into IgG and ligand-affinity-purified fractions. These three preparations of the antibody gave an intense immunohistochemical signal in visceral yolk sac and developing liver, both of which are known to be major producers of transferrin in early development. In immunoblot analysis, these three preparations detected 70-kDa transferrin, whereas the ligand-affinity purified preparation showed higher specificity. It was also demonstrated by enzyme-linked immunosorbent assay and immunoblotting that Toraji 3 antibody bound preferentially to chicken transferrin and showed a negligible binding to human transferrin. PMID- 8207508 TI - Microvascular decompression for trigeminal neuralgia caused by vertebrobasilar compression. AB - Thirty-one (2%) of 1404 consecutive patients with typical trigeminal neuralgia who underwent microvascular decompression between 1972 and 1993 were found to have vascular compression by the vertebral artery (VA) or the basilar artery (BA). Compared to the remaining 1373 patients, this subgroup was older (mean age 62 vs. 55 years, p < 0.001), was predominantly male (68% vs. 39%, p < 0.002), demonstrated left-sided predominance (65% vs. 39%, p < 0.002), was more likely to be hypertensive (65% vs. 18%, p < 0.001), and was more likely to have ipsilateral hemifacial spasm (16% vs. 0.6%, p < 0.001). The trigeminal nerve was compressed by the VA in 18 cases (the VA alone in three and the VA plus other vessels in 15), the BA in 12 cases (the BA alone in four and the BA plus other vessels in eight), and the vertebrobasilar junction in one case. Twenty-nine of the 31 patients underwent vascular decompression of the trigeminal nerve, one had a complete trigeminal root section, and one underwent partial root section with vascular decompression of the remaining nerve. All 31 patients were pain-free, off medication immediately after surgery, and this pain-free, medication-free status was maintained at 1 year after surgery in 96% of cases, at 3 years in 92%, and at 10 years in 86%, based on life-table analysis. Minor trigeminal hypesthesia/hypalgesia was present preoperatively in 52%. New or worsened minor hypesthesia/hypalgesia developed in 41% of patients, while transient diplopia as well as hearing loss developed in 23% and 13% in the overall series, respectively. No patient developed major trigeminal sensory loss or masseter weakness after vascular decompression alone. There was no operative mortality. Vascular decompression is an effective treatment for patients with trigeminal neuralgia who have vertebrobasilar compression of the trigeminal nerve. Patients should be warned that decompression of a tortuous vertebrobasilar system carries a higher risk of mild trigeminal dysfunction, diplopia, and hearing loss than standard microvascular decompression. PMID- 8207509 TI - Treatment of invasive growth hormone pituitary adenomas with long-acting somatostatin analog SMS 201-995 before transsphenoidal surgery. AB - The purpose of this study was to determine whether the long-acting somatostatin analog SMS 201-995 (octreotide) shrinks growth hormone (GH)-secreting adenomas and improves the results of subsequent transsphenoidal surgery. Ten previously untreated active acromegalic patients (nine women and one man) with invasive tumors were treated with SMS 201-995 (100 micrograms subcutaneously every 8 hours) for 6 weeks prior to transsphenoidal surgery. The clinical activity, mean GH secretion, insulin-like growth factor (IGF)-I concentration, and tumor volume were measured under basal conditions and on Days 14, 28, and 42 of treatment. The SMS 201-995 improved the symptoms of acromegaly in all patients. Mean levels of both GH and IGF-I (+/- standard deviation) were significantly decreased by Day 14 (from 92.9 +/- 30.5 to 44.9 +/- 20.3 micrograms/liter and from 10.6 +/- 7.4 to 5.9 +/- 2.6 U/ml, respectively), after which there were only slight further decreases. Six (60%) of the 10 patients experienced tumor shrinkage ranging from 9% to 78% (mean 30%). When it occurred, tumor shrinkage was significant by Day 14 (7.9 +/- 6.3 to 6.5 +/- 5.1 cu cm) and no further shrinkage was achieved by longer administration. Transsphenoidal surgery reduced postoperative GH levels to less than 2 micrograms/liter and IGF-I to less than 1.5 U/ml in six patients (60%). This percentage of cure is higher than expected from the literature and the authors' previous experience. However, an investigation of the influence of this drug on several parameters, such as reduction of tumor size or GH and IGF-I concentrations, has failed to prove any relationship. Only pretreatment size of the tumor was of predictive value with respect to the surgical outcome. PMID- 8207510 TI - Stenosis of the central canal of the spinal cord following inoculation of suckling hamsters with reovirus type I. AB - The central canal of the human spinal cord is partially or completely occluded in the vast majority of individuals by the early years of adult life. The authors describe an experimental lesion following virus-induced ependymitis that bears a striking resemblance to the condition in man. Suckling hamsters were inoculated with 0.06 ml of 10(-3) infectivity titer of reovirus type I between the 2nd and 5th days of life. The pathological events consisted of necrotizing ependymitis, healing of the ependyma by gliovascular scarring, and obstruction of narrow bottlenecks such as the central canal. Histological findings were characterized by disorganization of the ependyma, formation of ependymal rosettes and microtubules, subependymal gliovascular scarring, and intracanalicular gliosis. These features are the same as those encountered clinically and provide strong evidence that stenosis of the central canal in man is a pathological lesion involving ependymal injury and scarring. PMID- 8207511 TI - Brachial plexus repair by peripheral nerve grafts directly into the spinal cord in rats. Behavioral and anatomical evidence of functional recovery. AB - Over the years, peripheral nerve grafts, a favorable environment for the support of axonal elongation, have attracted interest as a possible means of promoting spinal cord repair. In the experiments described here, rats underwent an avulsion injury of the brachial plexus, and the musculocutaneous nerve was repaired by direct insertion of peripheral nerve grafts into the spinal cord. After varying postoperative periods, the rats were submitted to a series of behavioral tests to evaluate forelimb and hindlimb function. They also underwent retrograde double labeling studies. Nerve grafts were harvested and processed for electronic microscopy. The biceps muscle was removed and weighed and its histology studied. After surgery, central axons effectively regenerated about 65 mm along the peripheral nerve grafts, restoring normal active elbow flexion. Forelimb movements were well coordinated in both voluntary and automatic activities. Clinical investigations showed that there were no side effects in the ipsilateral forepaw, contralateral forelimb, or either hindlimb. Regenerating axons stemmed from original motoneurons, foreign motoneurons, and even antagonist motoneurons, but this did not impair function. Ganglionic neurons from adjacent roots also sent processes to the peripheral nerve grafts. PMID- 8207512 TI - Postoperative mutism in neurosurgery. Report of two cases. AB - Mutism is defined as a state in which a patient is conscious but unwilling or unable to speak. It has been reported to occur in association with a multitude of conditions, including trauma, epilepsy, tumors, stroke, psychoses, and brain surgery. The cases of two patients who became mute in the immediate postoperative period are presented. The first patient developed mutism following removal of a parasagittal meningioma, and the second following removal of a posterior fossa medulloblastoma. It is believed that transient injury may have occurred to the supplementary motor cortex in the first case and to the dentate nuclei in the second case. It is interesting that these two areas are connected via pathways involving the ventrolateral nucleus of the thalamus, and that lesions of this thalamic nucleus can also lead to mutism. It therefore appears plausible that interruption of these pathways may be involved in the pathogenesis of mutism. Although mutism is an infrequent complication of brain surgery, neurosurgeons should be aware that it may occur following removal of lesions in these areas and that it is generally a transient condition. PMID- 8207513 TI - Primary empty sella in association with superior sagittal sinus thrombosis and dural arteriovenous malformation. Case report. AB - A 61-year-old woman under treatment with oral medroxyprogesterone acetate following surgery for breast cancer developed diplopia and papilledema due to raised intracranial pressure (ICP). Radiological studies disclosed an empty sella turcica, a dural arteriovenous malformation (AVM), and superior sagittal sinus thrombosis. The sinus thrombosis was considered to have been a side effect of the medroxyprogesterone acetate medication. The association between a primary empty sella and raised ICP is briefly discussed, along with the cause-and-effect relationship between a dural AVM and venous sinus thrombosis. PMID- 8207514 TI - Hindbrain herniation: an unusual occurrence after shunting an intracranial arachnoid cyst. Case report. AB - The case is presented of a prepontine arachnoid cyst in a 28-year-old woman. She was treated by craniotomy, stereotactic aspiration, internal shunting, and finally by insertion of a cystoperitoneal shunt. Eight months later she developed an asymptomatic Arnold-Chiari type I malformation. The pathogenesis of this unusual hindbrain herniation is explained on the basis of the differential pressure between two compartments and cephalocranial disproportion. PMID- 8207515 TI - Hypothalamic chordoma. Case report. AB - The case is reported of a 51-year-old woman found to have a hypothalamic mass with the histological features typical of chordoma. This represents the first description of a chordoma arising within the brain. PMID- 8207516 TI - Lhermitte-Duclos disease and Cowden's syndrome in an adolescent patient. Case report. AB - Recent reports of seven cases of Lhermitte-Duclos disease occurring in adult patients with Cowden's syndrome (multiple hamartoma syndrome) strongly suggest that Lhermitte-Duclos disease is one of the types of neoplasia that characterize this syndrome. A case of Lhermitte-Duclos disease is reported in a 16-year-old girl with craniomegaly, choroidal hamartoma, and conjunctival papilloma of the right eye, and a history of bilateral multinodular adenomatous goiter and cystic hygroma. These findings strongly suggest a diagnosis of Cowden's syndrome. Although the syndrome traditionally has been defined by mucocutaneous criteria, it typically also involves hamartomas and neoplasia of internal organs, most commonly in the thyroid, breast, and female genitourinary tract. Because the mucocutaneous features may develop several decades after birth, the present case both supports the previously reported association between Lhermitte-Duclos disease and Cowden's syndrome and highlights the need for long-term follow-up monitoring of a pediatric patient with Lhermitte-Duclos disease because of the risk of malignancies associated with Cowden's syndrome. PMID- 8207517 TI - High cervical pain and impairment of skull mobility as the only symptoms of an occipital condyle fracture. Case report. AB - Occipital condyle fractures are rarely reported in survivors of trauma. Most cases involve patients with a major head trauma, lower cranial nerve palsy, and/or suspected lesions demonstrated on plain x-ray films of the skull or cervical spine. The authors describe a traffic-accident victim in whom an atlanto occipital joint lesion was suspected based only on mobility investigation of the skull. Axial high-resolution computerized tomography of the atlanto-occipital joint showed a fracture of the right occipital condyle. PMID- 8207518 TI - Basilar artery dissection: an early postoperative complication of aneurysm clipping. Case report. AB - Recurrent subarachnoid hemorrhage (SAH) in the early period following successful clipping of a cerebral aneurysm is unusual. The authors report a unique case of distal basilar artery dissection and fatal SAH on the 6th day postoperatively. It is concluded that this complication was related to vascular trauma inflicted by repositioning the aneurysm clips during a seemingly uneventful procedure for a basilar artery tip aneurysm. PMID- 8207519 TI - Treatment of high-dose intrathecal morphine overdose. Case report. AB - The case is reported of a 45-year-old woman who was being treated for chronic back and right leg pain with intrathecal morphine administered via a subcutaneous continuous-infusion device. She received an accidental 450-mg bolus injection of morphine intrathecally and developed hypertension, status epilepticus, intracerebral hemorrhage, and respiratory failure. Treatment with continuous intravenous naloxone infusion, lumbar catheter drainage of cerebrospinal fluid, and control of hypertension and status epilepticus resulted in an excellent outcome with return to neurological baseline. Care providers who refill pump reservoirs with morphine must be knowledgeable about these devices and the life threatening consequences associated with errors in refilling them. This case describes the complications and successful treatment of high-dose intrathecal morphine overdose. PMID- 8207520 TI - The Journal of Neurosurgery in the computer era. AB - The fourth Editor of the Journal of Neurosurgery offers short vignettes on the Editors who preceded and succeeded him. He recounts some of the challenges that were faced and changes that were made during his time as Editor. One of the major changes was production of the Journal via computer. PMID- 8207521 TI - Surgery for occult aneurysms. PMID- 8207522 TI - Subarachnoid hemorrhage and choir singing. PMID- 8207523 TI - Extracerebral fluid collections in infancy: role of magnetic resonance imaging in differentiation between subdural effusion and subarachnoid space enlargement. AB - The pathological process of extracerebral fluid collections in infancy includes subdural effusion and enlargement of the subarachnoid spaces. Both conditions have traditionally been investigated as a single clinical entity, because of difficulty in differentiating between them. The prognosis of subdural effusion is not as benign as that of enlargement of subarachnoid spaces, requiring differential diagnosis between these disorders. The present study was conducted to elucidate whether this differentiation could be made on magnetic resonance (MR) images. The series consisted of 16 infants aged 10 months or younger, including eight with verified subdural effusion and eight in whom a diagnosis of enlargement of the subarachnoid spaces was achieved by neuroimaging studies other than MR imaging. In all eight patients with subdural effusion, the intensity of the fluid was greater than that of cerebrospinal fluid (CSF) in at least one of the sequences using T1-weighted, proton-density, and T2-weighted MR images. The flow-void sign, indicating vessels in the fluid spaces, was not seen in any of these eight patients. On the other hand, in all eight patients with enlargement of the subarachnoid spaces, the fluid was isointense in relation to CSF, and vascular flow-void areas were seen in at least one of the MR imaging sequences. Based on these observations, it is concluded that differentiation between subdural effusion and enlargement of the subarachnoid spaces can be established by focusing on two aspects of MR imaging findings: 1) the intensity of the fluid, which is either iso- or hyperintense relative to CSF, and 2) the presence or absence of vascular flow-void areas in the fluid spaces. PMID- 8207524 TI - Treatment options and prognosis for multicentric juvenile pilocytic astrocytoma. AB - Little is known about the risk of developing multicentric disease in patients with juvenile pilocytic astrocytoma (JPA), and even less about its prognosis. Only five cases have been reported. Between 1986 and 1992, the authors treated 90 patients with either primary or recurrent JPA, 11 of whom developed multicentric spread. Ten patients had primary tumors in the hypothalamic region, eight were under 4 years of age at initial diagnosis, all had initially undergone a subtotal resection or biopsy, and 10 received postoperative multiagent chemotherapy or irradiation for residual disease. Multicentric spread was discovered immediately to 108 months after initial diagnosis; nine patients were asymptomatic at the time. Most patients received chemotherapy for the multicentric disease, which was found throughout the craniospinal axis. During 21 to 148 months of follow-up monitoring, seven patients had stabilization or regression of multicentric disease and four died. Patients with hypothalamic region tumors were 23 times more likely to develop multicentric spread than were those with primary tumors located elsewhere (p < 0.001). Based on this review, it is concluded that multicentric spread of JPA occurs more frequently than was previously recognized. In patients with subtotally resected JPA and several years of follow-up review via magnetic resonance imaging, the incidence of recurrence in a site different from the original was 12%. Patients with subtotally resected JPA in the hypothalamic region should be considered to be at high risk for developing multicentric spread. Chemotherapy appears useful in stabilizing multicentric disease. Earlier detection and intervention may result in longer disease-free survival in patients with multicentric spread of JPA. PMID- 8207525 TI - Reoperation for recurrent temporal lobe epilepsy. AB - The indications for the risks and outcome of reoperation for medically refractory temporal lobe epilepsy have not been well documented. A retrospective review is presented of 40 patients who underwent reoperation on the temporal lobe for recurrent seizures. The mean patient age at the first operation was 22 +/- 7 years (+/- standard deviation). Electrocorticography during the first operation showed interictal epileptic abnormalities from surface electrodes in 97% of the cases and from depth electrodes in the mesiotemporal structures in 38%. The seizures recurred with the same pattern within 6 months after the first operation in 60% of patients and within 2 years in 90%. Postoperative neuroimaging studies showed residual mesiotemporal structures in all cases. The mean time between the two operations was 5.5 +/- 5 years and the mean patient age at the second operation was 28 +/- 8 years. The second operation involved focal resection of the mesiotemporal structures in 30 cases. The mean postoperative follow-up period was 4.8 +/- 2.7 years (range 2 to 11 years). After the second operation, 63% of the patients were seizure-free or had rare seizures (one or two per year). There were no permanent neurological complications. Patients who did not benefit from reoperation had electroencephalographic abnormalities in multiple brain areas. Reoperation for temporal lobe epilepsy effectively controls seizures in the majority of patients, and the procedure is safe if rigorous technical rules are observed. More complete resection of mesiotemporal structures during the first operation, even in the absence of intraoperative electrographic abnormalities, could prevent the need for reoperation in defined cases. PMID- 8207526 TI - Cervicomedullary compression in achondroplasia. AB - Six patients with achondroplasia and symptoms suggestive of cervicomedullary junction compression are reviewed; these included three females and three males, with an average age of 8 years (range 7 months to 30 years). The mean duration of symptoms prior to intervention was 1.9 years. Symptoms included occipitocervical pain, ataxia, incontinence, apnea, and respiratory arrest. Radiological investigations consisted of plain films with flexion and extension views, pluridirectional tomography, thin-section computerized tomography, and magnetic resonance imaging. Typical findings included marked foramen magnum stenosis, ventrolateral cervicomedullary junction compression secondary to central and paramesial basilar invagination, and dorsal cervicomedullary junction compression secondary to ligamentous hypertrophy and invagination of the posterior atlantal arch. All patients underwent posterior fossa decompression and atlantal laminectomy. Surgery consistently revealed marked dorsal and paramesial overgrowth of the rim of the rim of the foramen magnum, with thickening and invagination of the atlantal posterior arch and a dense fibrotic epidural band resulting in dorsal cervicomedullary compression. Intraoperative ultrasonography was used to determine the extent of decompression required. Three patients required duraplasty. Three patients had concurrent hydrocephalus, two of whom had undergone ventriculoperitoneal shunting prior to surgical decompression of the posterior fossa. One patient developed a pseudomeningocele postoperatively, requiring serial lumbar punctures before it resolved. No patient developed craniovertebral instability following decompression. Improvement or resolution of symptoms was noted in all patients, with an average follow-up period of 4.8 years. Thus, cervicomedullary compression in patients with achondroplasia can be successfully treated with dorsal decompression of the craniovertebral junction. Dense epidural fibrotic bands are frequently noted in these cases and must be aggressively released to ensure satisfactory decompression. PMID- 8207527 TI - Extreme lateral transcondylar approach: technical improvements and lessons learned. AB - An extreme lateral transcondylar or extreme lateral transfacetal surgical approach was used to treat 22 patients with complex lesions over a 22-month period. The lesions included basilar invagination with vertebral artery pathology, giant aneurysm or arteriovenous fistula of the vertebral artery, meningioma, chordoma, chondrosarcoma, and paraganglioma. The approach was used alone or in combination with a presigmoid petrosal or subtemporal-infratemporal approach. Refinements of the operative technique, treatment strategies for complex lesions, and the avoidance of complications are discussed. Complications included cerebrospinal fluid leakage, meningitis, pseudomeningocele, hemiparesis or quadriparesis, lower cranial nerve deficits, and vertebral artery injury requiring repair. With treatment, major neurological deficits resolved completely in three patients and partially in two. There was no operative mortality, but four patients died during the follow-up period. For the 18 surviving patients, the mean preoperative and postoperative Karnofsky scores were 81 and 93, respectively. For the four who died, the mean preoperative Karnofsky score was 73 and the mean postoperative score was 63. PMID- 8207528 TI - The far lateral/combined supra- and infratentorial approach. A human cadaveric prosection model for routes of access to the petroclival region and ventral brain stem. AB - A far lateral approach to the ventral brain stem, lower clivus, and anterior foramen magnum is described. Methods for further exposure of the superior petroclival region by incorporating a subtemporal craniotomy and posterior petrosectomy are also demonstrated. Eight sequentially illustrated steps depict this technique. The far lateral/combined supra- and infratentorial exposure is a comprehensive surgical approach that provides direct access to the entire anterior and lateral brain stem and craniovertebral junction. It minimizes brain stem retraction and maximizes visualization of the neurovascular structures. PMID- 8207529 TI - Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors. AB - The role of matrix metalloproteinases (MMP's) and their inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1), in human brain tumor invasion was investigated. Gelatinolytic activity was assayed via gelatin zymography, and four MMP's (MMP-1, MMP-2, MMP-3, and MMP-9) and TIMP-1 were immunolocalized in human brain tumors and in normal brain tissues using monoclonal antibodies. The tissue was surgically removed from 44 patients: glioblastoma (five cases), anaplastic astrocytoma (six cases), astrocytoma (four cases), metastatic tumor (six cases), neurinoma (10 cases), meningioma (10 cases), and normal brain tissue (three cases). Glioblastomas, anaplastic astrocytomas, and metastatic tumors showed high gelatinolytic activity and positive immunostaining for MMP's; TIMP-1 was also expressed in these tumors, but some tumor cells were negative for the antibody. Astrocytomas had low gelatinolytic activity and the tumor cells showed no immunoreactivity for MMP's and TIMP-1. Although neurinomas and meningiomas had only moderate proteinase activity and exhibited positive immunoreactivity for MMP 9, intense expression of TIMP-1 was simultaneously observed in these tumor cells. These findings suggest that MMP's play an important role in human brain tumor invasion, probably due to an imbalance between the production of MMP's and TIMP-1 by the tumor cells. PMID- 8207530 TI - Transcranial approach to the orbit: microsurgical anatomy. AB - An anatomical study of three microsurgical intraorbital routes to the optic nerve and orbital apex, which can be reached through a fronto-orbital craniotomy, was conducted on cadaver specimens. The structures that could be exposed via the medial, central, or lateral approaches directed through the orbital roof were defined. The medial approach, directed through the space between the superior oblique and the levator muscles, provides good access to all parts of the intraorbital optic nerve. The central approach, between the levator and the superior rectus muscles, provides the shortest route to the optic nerve. Two variants of the central approach were examined. In the first, the levator muscle and frontal nerve are retracted medially and the superior rectus muscle laterally. This variant provides access to only the midportion of the intraorbital segment of the optic nerve. In the second variant, the frontal nerve is retracted laterally together with the superior rectus muscle. This variant provides access to the posterior two-thirds of the intraorbital portion of the optic nerve. The lateral approach is directed between the levator and lateral rectus muscles. This approach also has two variants, depending on whether the superior ophthalmic vein is retracted medially or laterally. The variant in which the superior ophthalmic vein is retracted medially with the levator and superior rectus muscles provides access to the lateral side of the optic nerve except in the region adjacent to the superior orbital fissure. The variant in which the superior ophthalmic vein is retracted laterally together with the lateral rectus muscle provides excellent access to the optic nerve in the region of the superior orbital fissure. It is an ideal approach for lesions that involve both the cavernous sinus and orbit. PMID- 8207531 TI - Cytotoxic effects of bloody cerebrospinal fluid on cerebral endothelial cells in culture. AB - The release of intracellular products from lysed blood cells is believed to play a critical role in the etiology of vascular pathology following intracerebral hemorrhage. The present studies investigated the effects of a mixture of blood and cerebrospinal fluid (CSF) on bovine intracranial endothelial cells maintained in culture. The incorporation of 3H-leucine into endothelial cells was used as an index of cellular viability. Cerebrospinal fluid alone did not alter the incorporation of 3H-leucine into the cells. In contrast, CSF preincubated with blood for 3 days or longer prior to treatment elicited significant reductions in leucine incorporation. Treatment with CSF preincubated with blood for 5 to 7 days resulted in the rapid deterioration of the culture, with large numbers of cells detaching almost immediately. Concentrations of hemoglobin were elevated profoundly in mixtures of blood and CSF preincubated for periods longer than 3 days. The increases in hemoglobin concentration were related temporally to increases in the cytotoxic impact of the bloody CSF. These findings suggest that factors released during the breakdown of blood exert a deleterious effect on intracranial endothelial cells. The time course of this effect is closely related to the development of vasospasm in humans following subarachnoid hemorrhage. Taken together, these observations are consistent with the hypothesis that intracellular blood products, particularly hemoglobin, contribute to vasospasm by directly compromising endothelial function. PMID- 8207532 TI - Experimental intracerebral hemorrhage: relationship between brain edema, blood flow, and blood-brain barrier permeability in rats. AB - There have been few investigations of brain edema formation after intracerebral hemorrhage (ICH), despite the fact that mass effect and edema are important clinical complications. The present study was designed to investigate the time course for the formation and resolution of brain edema and to determine how changes in cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability are temporally related to edema formation following ICH. Anesthetized adult rats received a sterile injection of 100 microliters of autologous blood into the caudate nucleus. Water and ion contents were measured immediately, at 4 and 12 hours, and daily to Day 7 (10 time points, six rats at each time) after experimental ICH. The water content of the ipsilateral basal ganglia increased progressively (p < 0.002) over the first 24 hours, then remained constant until after Day 5, when the edema began to resolve. Edema was most severe in the tissue immediately surrounding the hemorrhage; however, it was also present in the ipsilateral cortex, the contralateral cortex, and the basal ganglia. Measurements of local CBF (using [14C]-iodoantipyrine) and BBB permeability (using [3H]-alpha aminoisobutyric acid) were obtained in separate groups of six to eight rats at various time intervals between 1 and 48 hours after ICH. Cerebral blood flow was reduced to 50% of control at 1 hour, returned to control values by 4 hours, but then decreased to less than 50% of control between 24 and 48 hours after ICH. The BBB permeability increased significantly prior to the occurrence of significant edema in the tissue surrounding the clot. However, BBB permeability in the more distant structures remained normal despite the development of edema. These results demonstrate a time course for the formation and resolution of brain edema following ICH similar to that observed during focal ischemia. Brain edema forms in the immediate vicinity of the clot as a result of both BBB disruption and the local generation of osmotically active substances and then spreads to adjacent structures. While local ischemia, due to the mass effect of the hemorrhage, may play a role in producing cytotoxic and vasogenic edema, the release of toxic substances from the clot should also be considered. Since edema is nearly maximal by 24 hours after ICH, therapy directed at reducing edema formation must be instituted within the 1st day. PMID- 8207533 TI - Opportunities in the nutrition and food sciences: research challenges and the next generation of investigators. Special Committee of the Food and Nutrition Board of the Institute of Medicine, National Academy of Sciences. PMID- 8207534 TI - Somatotropin alters collagen metabolism in growing pigs. AB - Treatment of pigs with porcine somatotropin (pST) is associated with altered nutrient partitioning. The aim of this investigation was to determine the role of pST in protein and collagen deposition in growing pigs. Barrows were treated daily with buffer or pST when they weighed between 30 and 64 kg (n = 8 pigs/group). Pigs were restrictively fed such that the average feed intake for both groups was 1.86 kg/d. Treatment with pST was associated with 25, 55, 78 and 31% higher growth rates for carcass, skin, viscera and head, respectively. Total protein depositions (g/d) were 52, 60, 81, 42 and 54% greater in carcass, skin, viscera, head and empty body, respectively, of pST-treated pigs. Collagen represented approximately 70, 15 and 43% of total protein in skin, viscera and head; pST did not influence this ratio. However, collagen relative to total protein was 16% lower in the carcass of pST-treated pigs. Deposition rate of collagen was higher in all components of empty body, except carcass, as a result of pST treatment. The ratio of non-collagen protein to collagen deposition rate was 49% greater in the carcass of pST-treated pigs. The deposition rate of acid soluble collagen was approximately 2-fold higher in skin but was 25% lower in carcass of pST-treated pigs. Depositions of insoluble collagen in viscera and head of pST-treated pigs were 74 and 46% greater, respectively, than for controls. These data show that pST treatment enhances collagen deposition in skin, head and viscera, whereas non-collagen protein deposition and collagen maturation are enhanced in the carcass. PMID- 8207535 TI - Indolic compounds affect tryptophan binding to rat hepatic nuclei. AB - This study evaluates the effects of indolic or indole-related compounds on binding of L-tryptophan (saturable, stereospecific and of high affinity) to rat hepatic nuclei or nuclear envelopes. Addition of any one of many indolic or indole-related compounds, and particularly of 3-methylindole, does not inhibit in vitro binding of [3H]tryptophan to hepatic nuclear envelopes. However, when 3 methylindole (10(-10) to 10(-4) mol/L) is added in combination with unlabeled L tryptophan (10(-4) mol/L), it diminishes the inhibitory effect of unlabeled L tryptophan alone. Scatchard analysis of the binding affinities of in vitro [3H]tryptophan binding to hepatic nuclear envelopes using L-tryptophan in the absence or presence of 3-methylindole reveals similar dissociation constants (KD) under the two conditions, but the binding concentrations (Bmax) were greater in the combined group compared with that in the L-tryptophan alone group. Addition of 3-methylindole to liver before homogenization decreases specific [3H]tryptophan binding to nuclei compared with controls (without addition). L Tryptophan tube-fed to rats with or without 3-methylindole administration increases in vitro hepatic protein synthesis compared with that of saline tube fed controls. 3-Methylindole itself does not affect protein synthesis. Our report describes the effects of 3-methylindole on specific tryptophan binding to hepatic nuclear envelope receptor and discusses the possible implications thereof. PMID- 8207536 TI - Low levels of ATP synthase and cytochrome c oxidase subunit peptide from hearts of copper-deficient rats are not altered by the administration of dimethyl sulfoxide. AB - This study determined if reported decreases in the delta subunit of ATP synthase and nuclear-encoded cytochrome c oxidase subunits in hearts of copper-deficient rats were secondary to the heart disease pathology or due to lack of the trace element. Male weanling Long-Evans rats were randomly divided into six groups: rats fed a copper-adequate or copper-deficient diet (with free access) with or without 5% dimethyl sulfoxide (DMSO) in the drinking water and rats pair-fed the copper-adequate or copper-deficient diet without DMSO treatment. After 4 wk, rats in the groups fed the copper-deficient diet had lower liver superoxide dismutase and heart cytochrome c oxidase activities compared with groups fed the copper adequate diet. Administration of DMSO, an antioxidant, and energy restriction (pair-feeding) partially blocked cardiac hypertrophy in rats fed the copper deficient diet. Greater mitochondrial volume density and mitochondrial:myofibrillar ratio and disrupted myofibrils and basal laminae were observed in the hearts from rats fed the copper-deficient diet and not treated with DMSO compared with hearts from groups fed the copper-adequate diet. The DMSO treated rats fed the copper-deficient diet had hearts with intact structure but enlarged mitochondria compared with other groups fed the copper-deficient diet. The delta subunit of ATP synthase and the nuclear-encoded cytochrome c oxidase subunits IV and V were depressed in rats fed a copper-deficient diet regardless of antioxidant treatment and pair-feeding. These data suggest that the effects of copper deficiency upon ATP synthase and cytochrome c oxidase proteins are not due to the cardiac pathology. PMID- 8207537 TI - Vagotomy and mercaptoacetate influence the effect of dietary fat on macronutrient selection by rats. AB - We have previously shown that rats fed saturated fat prefer a high protein, low carbohydrate diet, whereas animals fed unsaturated fat prefer a low protein, high carbohydrate diet. The purpose of the present study was to determine whether this "saturated fat effect" requires 1) the oxidation of the dietary fat and 2) an intact hepatic vagus nerve. Male Sprague-Dawley rats were vagotomized (hepatic branch) or sham-operated and injected with either mercaptoacetate (fatty acid oxidation inhibitor) or saline. Next, half of each group was given saturated fat (beef tallow) or unsaturated fat (corn oil) by gastric tube. All animals were given a choice between two mixed diets that differed in protein and carbohydrate. Sham-operated rats fed saturated fat ate more of the protein diet than did rats fed unsaturated fat. Vagotomy attenuated the intake of the protein diet in animals fed saturated fat. Mercaptoacetate or vagotomy had no effect on diet selection in rats fed unsaturated fat. These data indicate that the effect of saturated fat on diet selection requires an intact hepatic vagus and may be modulated by fatty acid oxidation. Furthermore, the mechanism for altering diet selection can be induced after a single meal. PMID- 8207538 TI - Detection and localization of lipid peroxidation in selenium- and vitamin E deficient rats using F2-isoprostanes. AB - Data on the effect of vitamin E and selenium deficiency on lipid peroxidation in vivo have been limited. F2-isoprostanes are novel prostanoids that, free in plasma and esterified to phospholipids in tissues, are markers of lipid peroxidation in vivo. To address the importance of vitamin E and selenium in defense against lipid peroxidation in vivo, we determined F2-isoprostane concentrations in the plasma and organs of rats fed diets deficient in one or both nutrients. Weanling rats were fed a vitamin E- and selenium-deficient diet for 12 wk and then divided into four groups. One group continued to receive the doubly deficient diet, and the other three groups were fed the diet supplemented with vitamin E, selenium or both nutrients (control diet) for 4 wk. Plasma F2 isoprostanes in rats fed the doubly deficient diet were 5.2-fold higher than in animals changed to a control diet. In addition, there were significant differences in liver, lung, kidney, heart and skeletal muscle phospholipid esterified F2-isoprostanes between these two groups. Lesser increases were noted in the group fed the vitamin E-deficient diet. Selenium deficiency alone was not associated with greater lipid peroxidation. Lipid peroxidation occurs in tissues of rats fed a vitamin E-deficient diet and is increased by concomitant selenium deficiency. PMID- 8207539 TI - Prickly pear (Opuntia sp.) pectin alters hepatic cholesterol metabolism without affecting cholesterol absorption in guinea pigs fed a hypercholesterolemic diet. AB - Prickly pear pectin intake decreases plasma LDL concentrations by increasing hepatic apolipoprotein B/E receptor expression in guinea pigs fed a hypercholesterolemic diet. To investigate whether prickly pear pectin has an effect on cholesterol absorption and on enzymes responsible for hepatic cholesterol homeostasis, guinea pigs were fed one of three semipurified diets, each containing 15 g lard/100 g diet: 1) the lard-basal diet with no added cholesterol or prickly pear pectin (LB diet); 2) the LB diet with 0.25 g added cholesterol/100 g diet (LC diet); or 3) the LC diet containing 2.5 g prickly pear pectin/100 g diet, added at the expense of cellulose (LC-P diet). Animals fed the LB diet had the lowest plasma LDL and hepatic cholesterol concentrations, followed by animals fed the LC-P diet (P < 0.001). Hepatic 3-hydroxy-3 methylglutaryl CoA (HMG-CoA) reductase activity was highest in the group fed the LB diet, with similar values for animals in the other two groups. A positive correlation existed between plasma LDL cholesterol concentration and hepatic acyl CoA:cholesterol acyltransferase activity (r = 0.87, P < 0.001). Cholesterol absorption was not different among the three dietary groups. These results indicate that the decreased plasma and hepatic cholesterol concentrations of animals fed prickly pear pectin are not explained by differences in cholesterol absorption but rather are due to mechanisms that alter hepatic cholesterol homeostasis, resulting in lower plasma LDL concentrations. PMID- 8207540 TI - Daidzein is a more bioavailable soymilk isoflavone than is genistein in adult women. AB - Soybean isoflavones are proposed to be anticarcinogenic, but their effective doses have not been established. To study the bioavailability of soybean isoflavones for humans, 12 young adult women received single doses of 0.7, 1.3 and 2.0 mg isoflavones/kg body wt in soybean milk as part of a liquid diet. Plasma, urine and fecal isoflavones were measured by reverse-phase HPLC. Average 24-h urinary recoveries of daidzein and genistein were approximately 21% and 9%, respectively, at all three doses. Urinary recovery of daidzein was significantly greater than that of genistein (P < 0.001). Total fecal excretion of isoflavones was only 1-2% of the ingested amount. Plasma total isoflavone concentration was significantly increased to 4.4 +/- 2.5 mumol/L at 6.5 h after a dose of 2.0 mg/kg. The plasma concentrations of daidzein and genisten were approximately equal. Twenty-four hours after dosing, both plasma and urine isoflavone concentrations were nearly nil. Although soybean milk isoflavones seem to be 85% degraded in the intestine, the bioavailability, especially of daidzein, may be sufficient to exert some health-protective effects. PMID- 8207541 TI - Dietary fiber viscosity and amino acid digestibility, proteolytic digestive enzyme activity and digestive organ weights in growing rats. AB - The effect of dietary fiber viscosity on apparent ileal nitrogen and amino acid digestibility, proteolytic enzyme activity and digestive organ weights was investigated. Eighteen growing rats were fed for 21 d purified casein-based diets containing carboxymethylcellulose (50 g/kg) of low (20 cP), medium (800 cP) and high (2000 cP) viscosity (LV, MV and HV treatment groups, respectively). Dietary fiber viscosity did not significantly affect apparent ileal (terminal 15 cm of the ileum) nitrogen or amino acid digestibility, trypsin or chymotrypsin activity in the small intestinal contents and pancreatic tissue, aminopeptidase-N activity in the small intestinal contents and tissue, or the weights of the stomach, pancreas, small or large intestines. Intragastric pepsin activity in LV rats was significantly higher than in MV or HV rats (P < 0.01), but fiber viscosity did not affect pepsin activity in the stomach tissue. The intragastric pH of the HV and MV rats was significantly higher than that for the LV rats (P < 0.01). The stomach contents (dry matter) of MV and HV rats were greater than in LV rats (P < 0.05). Delayed passage rate of the more viscous digesta may have resulted in greater absorption of amino acids, because the HV rats had a higher estimated true ileal digestibility than the LV animals for threonine, serine, aspartic acid, glutamic acid, histidine, tyrosine and phenylalanine. PMID- 8207542 TI - A food-grade silicon dioxide is hypocholesterolemic in the diet of cholesterol fed rats. AB - Silicon dioxide, commonly referred to as silica, is present in plant cell walls and interstitial spaces, and is often found as a component of dietary fibers that have exhibited hypocholesterolemic activity in animals. The primary objective of this study was to determine the cholesterolemic effects of two different morphological forms of silicon in the diet of cholesterol-fed rats. Male Wistar rats were provided diets containing 1 g cholesterol/100 g diet, and 0.65 g Si/100 g diet as either a sodium salt (silicate group) or silicon dioxide, a synthetic silica polymer (silica group). Cellulose was used as a control (control group). The in vitro bile acid binding capacity of the SiO2 was also measured. After 44 d of diet administration, animals were deprived of food for 24 h and then killed. Plasma total, VLDL, and LDL cholesterol concentrations were 18%, 29%, and 26% lower, respectively, in the silica group than in the control group. However, liver cholesterol concentrations were not different among dietary treatments. During the initial 15 d of the study, average daily total fecal bile acids were 38% higher in the silica group than in the control group, but fecal bile acid outputs were not different for the remainder of the experiment. The silica polymer used in the feeding trial was found to adsorb 5 times more cholate than chenodeoxycholate, at pH 7.5 in vitro. In vivo, the potential for silica to enhance fecal cholic acid excretion, relative to chenodeoxycholic acid during the initial stage of the study, may have contributed to the hypocholesterolemic response to the silica diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207543 TI - [3H]inositol hexaphosphate (phytic acid) is rapidly absorbed and metabolized by murine and human malignant cells in vitro. AB - To test the hypothesis that the antineoplastic activity of phytic acid [inositol hexaphosphate (InsP6)] is a result of rapid intake by the cells and its conversion to lower inositol phosphates (InsP1-5), thereby affecting the intracellular inositol phosphate pool, YAC-1 (mouse T cell leukemia), K562 (human erythroleukemia) and HT-29 (human colon adenocarcinoma) cell lines were incubated at 37 degrees C with [3H]InsP6. After 1 h, 31.3 +/- 3.1% of administered radio activity was taken up by YAC-1 cells, 6.2 +/- 0.9% by K562 cells and 6.6 +/- 3.8% by HT-29 cells. Differential centrifugation and high resolution subcellular fractionation of cell homogenates demonstrated that within the various cellular compartments, 80% (HT-29) to 97% (YAC-1) of the total radioactivity was in the cytosol. Kinetic study showed that the peak of the total absorption was obtained after 30 min of cell exposure to radiolabeled InsP6, after with a plateau was reached. Analysis of the radioactivity accumulated within the cells showed variable proportions of myo-inositol and InsP1-6, with a preponderance of InsP1 and InsP2. The presence of [3H]myo-inositol and [3H]InsP1-6 suggests that InsP6 may, in some cells at least, be absorbed as such and that a variable degree of dephosphorylation of InsP6 takes place both extra- and intracellularly. PMID- 8207544 TI - Mongolian gerbils (Meriones unguiculatus) absorb beta-carotene intact from a test meal. AB - Because a yellow color has been observed in the fat pads of Mongolian gerbils fed a nonpurified diet, we designed the current study to determine whether adult male gerbils would absorb beta-carotene intact from a test meal. Thirty-five gerbils (80-90 g) were adapted to the laboratory and fed a standard purified diet free of beta-carotene for 16-19 d. Gerbils were then fed a test meal consisting of 279 nmol of beta-carotene as 10% water-soluble beadlets suspended in 0.5 mL of Ensure. Gerbils (n = 5) were killed at 0, 2, 4, 6, 12, 24 or 72 h after the test meal, blood was obtained by cardiac puncture, and tissues were taken for beta carotene analysis. No beta-carotene was detected in serum at 0 or 72 h, whereas beta-carotene was present at all other sampling times. Serum beta-carotene peaked at 4 h, at a level of 88 nmol/L. beta-Carotene was detected in the liver of all groups; however, the concentration increased from -34 pmol/g to a maximum concentration of 926 pmol/g at 24 h after the test meal. Other tissues also contained beta-carotene. The results demonstrate that Mongolian gerbils, like ferrets and preruminant calves, absorb beta-carotene intact when beta-carotene is provided at a physiological level in a test meal. This species may be particularly useful for evaluation of the role of antioxidants, such as beta carotene, in LDL oxidation. PMID- 8207545 TI - Bone repair in calcium-deficient rats: comparison of xylitol+calcium carbonate with calcium carbonate, calcium lactate and calcium citrate on the repletion of calcium. AB - The potential value of xylitol in calcium therapy was evaluated by comparing the effect of dietary xylitol (50 g/kg diet) + calcium carbonate with the effects of calcium carbonate, calcium lactate and calcium citrate on bone repair of young male rats after the rats consumed for 3 wk a calcium-deficient diet (0.2 g Ca/kg diet). After this calcium-depletion period, the rats were fed for 2 wk one of four diets, each containing 5 g Ca/kg diet as one of the four dietary calcium sources. The diet of the control animals was supplemented with CaCO3 (5 g Ca/kg diet) throughout the study. The Ca-deficient rats showed low bone mass, low serum calcium and high serum 1,25-dihydroxycholecalciferol, parathyroid hormone (1-34 fraction) and osteocalcin concentrations. They also excreted magnesium, phosphate and hydroxyproline in the urine in high concentrations, and had high bone alkaline phosphatase and tartrate-resistant acid phosphatase activities. Most of these changes were reversed by the administered of the calcium salts. The highest recoveries of femoral dry weight, calcium, magnesium and phosphate were observed in the groups receiving xylitol+CaCO3 and calcium lactate. Calcium lactate and calcium citrate caused low serum phosphate concentration compared with rats receiving CaCO3 and with the age-matched Ca-replete controls. Xylitol-treated rats excreted more calcium and magnesium in urine than did the other rats, probably due to increased absorption of these minerals from the gut. These results suggest that dietary xylitol improves the bioavailability of calcium salts. PMID- 8207546 TI - Absorption of nonheme iron in ascorbic acid-deficient rats. AB - Prior studies have shown that the absorption of dietary nonheme iron in rats is much higher and less responsive to dietary variables than in human subjects. The aim of the present study was to determine whether this dissimilarity is explained by species differences in ascorbic acid status or metabolism. Iron absorption studies were performed with normal rats and with a genetic strain that lacks the ability to synthesize the vitamin. Ascorbic acid deficiency was produced in these animals by removing supplemental vitamin C from the diet for a brief period before the study. Iron absorption was measured from meals tagged extrinsically with 59Fe and measured by whole-body counting. We studied the effect on iron absorption of adding meat, ascorbic acid, soybean, tea, or bran to the test meal. A significant but modest effect of bran on iron absorption was observed in normal rats and of ascorbic acid and tea in ascorbate-depleted animals. However, the overall sensitivity of rats to dietary facilitators or inhibitors of nonheme iron absorption was not altered dramatically by ascorbic acid depletion. The relative insensitivity of rats to dietary factors affecting nonheme iron absorption in humans is not explained by differences in ascorbic acid metabolism between rats and humans. PMID- 8207547 TI - Dietary arginine requirement of juvenile hybrid striped bass. AB - Two experiments were conducted to determine the dietary arginine requirement of juvenile hybrid striped bass (Morone saxatilis x M. chrysops); a third experiment evaluated the interaction of lysine and arginine. Diets in Experiments 1 and 2 were supplemented with graded concentrations of L-arginine-HCl, resulting in eight dietary treatments. Dietary arginine concentrations ranged from 1.0 to 2.4 g/100 g diet in Experiment 1 and from 0.6 to 2.0 g/100 g diet in Experiment 2. Weight gain was not affected by dietary treatments in Experiment 1. Feed efficiency was significantly affected by dietary arginine concentrations, and the data, when subjected to broken-line analysis, resulted in a requirement estimate of 1.53 +/- 0.20 g/100 g diet. Weight gain and feed efficiency were both significantly affected by dietary arginine concentrations in Experiment 2. Broken line analyses of weight gain and feed efficiency data indicated the dietary arginine requirement to be 1.55 +/- 0.10 and 1.45 +/- 0.12 g/100 g diet, respectively. Diets in Experiment 3 contained lysine and arginine in ratios of 1:1, 1:1.5, 1:2 and 1:2.5 for the previously estimated requirements for both lysine:arginine and arginine:lysine. No differences were observed in weight gain or feed efficiency for fish fed various lysine:arginine ratios, but serum lysine was significantly different among treatment groups. PMID- 8207548 TI - Marginal zinc status does not exacerbate pancreatic carcinogenesis associated with dietary soybean trypsin inhibitor concentrate in rats. AB - Although the etiology of pancreatic cancer is largely unknown, diet-associated factors may play a role. Male Sprague-Dawley rats (14 d of age) were given a single injection of either saline or azaserine and were weaned (21 d) to diets with either adequate (30 micrograms/g) or low (9 micrograms/g) zinc, with or without 1.0 g/100 g active trypsin inhibitor in the form of soybean trypsin inhibitor concentrate. Experimental diets were fed for 14 wk. Regardless of dietary zinc status, diets with soybean trypsin inhibitor concentrate caused hyperplasia and/or hypertrophy of the pancreas. Pancreatic zinc content was not different among groups. Low dietary zinc levels did not affect total body growth rate or serum zinc concentration. Tibia zinc was also used as an indicator of zinc status. Tibia zinc concentration was lower in rats fed diets low in zinc relative to adequate zinc diets. Azaserine-induced acidophilic foci were larger and more numerous when soybean trypsin inhibitor concentrate was present in the diet regardless of dietary zinc level. Thus, low zinc does not exacerbate the soybean trypsin inhibitor concentrate effects that promote pancreatic cancer. PMID- 8207549 TI - Preference for sodium chloride is reduced in protein-deprived juvenile rats. AB - The influence of dietary protein levels on the preference for sodium chloride was studied in juvenile rats fed diets containing 0, 25 or 50 g purified egg protein/kg and 20.0 mg zinc/kg diet. Preference tests between aqueous solution of NaCl (2-51 mmol/L) or deionized water were conducted. Blood samples were collected for measuring the serum zinc concentration. Scanning electron microscopy was performed to observe the rats' tongue epithelia. Only the rats fed 50 g purified egg protein/kg diet preferred the lowest concentration of 2 mmol/L NaCl solution to deionized water, whereas the rats fed protein-free diet did not discriminate diluted NaCl solution until the concentration was 9 mmol/L. The filiform papillae of the protein-free diet fed group showed significantly less development than the 25 g purified egg protein/kg and the 50 g purified egg protein/kg diet-fed groups. The more protein the diets contained, the higher was the serum concentration of zinc. Significant correlations were observed between protein intake and discriminated NaCl concentration (r = -0.93, P < 0.001), serum zinc (r = 0.90, P < 0.001) or length of filiform papillae (r = 0.93, P < 0.001). The present study suggests that taste preference is impaired by protein malnutrition and this may be related to zinc status. PMID- 8207550 TI - The RDA process: time for a change. PMID- 8207551 TI - Of voles and men. PMID- 8207552 TI - Partnerships in neonatal care: a model in reverse neonatal transport. AB - An agreement between a pediatric tertiary-care center and a community hospital provides a model of a program that has facilitated appropriate, cost-effective, high-quality care for high-risk neonates through reverse transport. This agreement has established trust between the professionals at both hospitals, increased communications to ensure continuity of care and psychosocial support for families, and obtained supplemental financial resources for families of high risk neonates. PMID- 8207553 TI - Ovarian hyperstimulation syndrome: protocols for nursing care. AB - One of the few life-threatening conditions encountered by the nurse caring for reproductive endocrinology and infertility patients is ovarian hyperstimulation syndrome (OHS). Having protocols for the nursing care of the patient with OHS enhances patient safety and quality of care. Model OHS protocols for outpatient and inpatient settings are presented. The collaborative nursing role in patient care also is discussed. PMID- 8207554 TI - The technology and use of blastomere analysis. AB - With the use of blastomere analysis, it is possible to screen for serious genetic disease before initiating pregnancy through in vitro fertilization. The analysis provides information about an embryo's genetic composition before implantation. This article describes the technique of blastomere analysis and its current and potential uses. Implications for nursing practice and education are identified. PMID- 8207555 TI - Maternal hypothermia: implications for obstetric nurses. AB - Hypothermia, a core body temperature of less than 95 degrees F (35 degrees C), is a common intraoperative complication among adult patients and may occur in obstetric patients. Obstetric patients are predisposed to hypothermia because of vasodilation from pregnancy, administration of anesthetics and pharmacologic agents, and inherent blood loss with rapid fluid replacement during delivery. Morbidity associated with hypothermia occurs from complications such as hypotension, cardiac arrhythmias, increased oxygen consumption or respiratory depression, and disseminated intravascular coagulation. Interventions include preventive measures such as maintaining reasonable ambient room temperatures, avoiding infusion of cold solutions, and promptly assessing postoperative temperature, as well as corrective measures--rewarming the patient, placing the patient on dry surfaces, minimizing additional heat loss, and providing external heat sources. PMID- 8207556 TI - Impact of maternal activity restriction for preterm labor on the expectant father. AB - OBJECTIVE: To describe the impact on expectant fathers of their partners' activity-restricted pregnancies. DESIGN: Qualitative. SETTING: Private physician practices and two teaching hospitals in a large southern city. PARTICIPANTS: Self selected sample of 15 fathers recruited within 2 weeks of initiation of their partners' activity restriction for high-risk pregnancy (phase 1) and 15 fathers recruited 1-2 years after a previous experience with their partners' activity restricted pregnancies (phase 2). DATA COLLECTION: In phase 1, two semistructured interviews during the period of activity restriction and one interview after the birth. In phase 2, one semistructured, focus group interview. RESULTS: Fathers reported high levels of worrying immediately after diagnosis of their partners' preterm labor and initiation of activity restriction. Later, fathers also reported distress related to responsibility for child care, household management, and maintaining a supportive environment for their partners. Fathers reported few sources of personal support and little or no contact with health professionals during their partners' activity restriction. CONCLUSIONS: Activity restriction during pregnancy may have a significant psychological impact on expectant fathers. High levels of emotional distress may result in family disruption. Systematic nursing assessment and intervention may prevent or ameliorate distress. PMID- 8207557 TI - Responses to vaginal birth after cesarean section. AB - OBJECTIVES: To compare women's reactions to their experiences of vaginal birth after cesarean (VBAC) with their reactions to their previous cesarean birth experiences, to identify the factors that influenced the women's decision to attempt VBAC, and to describe the causes the women ascribed to the outcome of their birth experiences. DESIGN: An exploratory descriptive study derived from the Roy Adaptation Model of Nursing. SETTING: Hospital postpartum unit. PARTICIPANTS: Thirty-two women who had experienced a VBAC. MAIN OUTCOME MEASURES: The Perception of the Birth Scale and an investigator-developed questionnaire. RESULTS: The women reported moderately positive perceptions of the VBAC experience. However, the mean score was lower than previously reported means for vaginally delivered women. A statistically significant association (X2 = 22.70, p < 0.0005) was found between type of delivery and adaptive and ineffective responses within the Roy Adaptation Model modes, with a greater proportion of adaptive responses to the VBAC than the previous cesarean. Information from obstetricians, nurses, family members, and print media influenced women's decisions to attempt the vaginal birth. Most causes ascribed to the successful VBAC came from external sources, were particular to a given pregnancy, and were beyond the woman's control. CONCLUSIONS: The women reported both positive and negative aspects of childbearing, regardless of mode of delivery. The results indicate a need for a high quality of nursing and obstetric care for all women, with an emphasis on relief of pain and the provision of support and information. PMID- 8207558 TI - Bone fragility: assessment of risk and strategies for prevention. AB - OBJECTIVE: To review the literature related to risk factors for bone fragility and strategies for prevention. DATA SOURCES: Computerized searches. STUDY SELECTION: All human research articles from indexed journals in the English language related to the topics in this review and published after 1982 (except for earlier classic pieces) were evaluated. DATA EXTRACTION: The author extracted data independently using tables that included the following headings: author, year, design, sample size, age range of subjects, results, and comments. Power analyses were done on all reports that included enough information. DATA SYNTHESIS: The following are determinants of bone fragility: peak bone mass, genetic influences, hormonal status, dietary factors, exercise patterns, and personal exposures. CONCLUSIONS: Women should be informed of the risk factors and helped to determine whether they are at risk for osteoporosis. All women, starting with young girls, should be taught what methods can be used to decrease their risk. Additional research is needed on methods of improving bone health and decreasing risk. PMID- 8207559 TI - Clinical aspects of parathyroid hypertensive factor. AB - Parathyroid hypertensive factor (PHF) in rats: PHF is an endogenous hypertensive substance which was originally associated with hypertension in spontaneously hypertensive rats (SHR). In this model, PHF was shown to act by increasing intracellular calcium levels in vascular smooth muscle and was linked with a characteristic pattern of abnormalities in overall calcium regulation. The action of PHF was blocked by calcium antagonists, suggesting that the effect of PHF was to increase extracellular calcium uptake. In SHR the parathyroid glands were shown to be the site of PHF secretion. This secretion was inhibited by an increase in dietary calcium. PHF was further shown to be unique to low-renin forms of hypertension, that is, those forms of hypertension characterized by abnormalities in calcium metabolism. PHF in humans: PHF was subsequently found in human low-renin salt-sensitive hypertension. As in SHR, calcium supplementation can lower PHF levels in humans. Similarly, there is circumstantial evidence for the parathyroid origin of PHF in humans. In human hypertensive patients, the presence of PHF has been shown to predict a favorable therapeutic response to calcium channel blockade. Recently, many of the abnormalities in calcium metabolism present in low-renin hypertension have also been described in other disease states. Notable among these diseases is non-insulin dependent diabetes mellitus. A survey of human non-insulin dependent diabetes mellitus has revealed that PHF was present in a disproportionate number of these patients independently of the blood pressure level. The significance of this latter finding needs to be explored, but PHF may prove to have relevance in diseases other than hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207560 TI - Endothelin plasma levels in hypertensive patients with vascular disease. AB - Physiology of endothelin: Circulating levels of immunoreactive endothelin-1 are very low, and below the level required for vaso-activity. It has a long duration of action but only 1-2 min of half-life. It is metabolized in the lungs, liver and kidney and is a profound constrictor of the pulmonary, renal, coronary and peripheral circulation. The prepro-endothelin-1 promoter contains an insulin responsive element. Inhibitory regulators include nitric oxide and prostacyclin. Endothelin in hypertension and cardiovascular disease: In both experimental animal and human hypertension, endothelin levels are not consistently reported to be elevated. They are, however, elevated in atherosclerosis, congestive cardiac failure and renal insufficiency. Since endothelin is a sensitive marker of endothelial injury, these elevated levels may simply reflect diffuse endothelial injury. The endothelium is a crucial factor in cardiovascular disease. Three important risk factors, ageing, hypertension and hypercholesterolaemia, are associated with a decreased basal and stimulated release of endothelium-derived nitric oxide. The release of endothelin-1 appears to increase with age while sensitivity to this peptide decreases. CONCLUSIONS: Endothelin may be a useful marker of end-organ damage, for example in atherosclerosis, but its pathogenic effects in hypertension remain unclear. PMID- 8207561 TI - Vascular effects of endothelin-1 in humans and influence of calcium channel blockade. AB - AIM: To investigate the effects of brachial artery infusions of endothelin-1 on forearm blood flow in normal healthy volunteers. METHODS: Brachial artery cannulation was used for a direct assessment of blood pressure and for intra arterial regional drug infusions. Drug-induced forearm blood flow changes were measured by venous occlusion plethysmography. RESULTS: Low-dose endothelin-1 infusions resulted in a significant increase in forearm blood flow, indicating vasodilation, which was significantly attenuated by cyclo-oxygenase inhibition using aspirin. High-dose endothelin-1 infusions resulted in transient vasodilation, followed by dose-dependent and long-lasting vasoconstriction. In the human forearm the vasoconstrictor potency of endothelin-1 was approximately 10-15 times greater than that of norepinephrine. Maximal cyclic GMP-dependent vascular muscle relaxation, after muscarinergic stimulation by acetylcholine (endothelium-dependent) or after infusion of sodium nitroprusside (endothelium independent), did not prevent endothelin-1 induced vasoconstriction. However, calcium channel blockade by brachial artery infusions of maximally vasodilating doses of either verapamil or nifedipine not only abolished the endothelin-induced vasoconstriction but also unmasked the vasodilator potency of high-dose endothelin-1 infusions. The infusion of lower doses of nifedipine indicated that endothelin-1 induced vasoconstriction was reversed by plasma concentrations estimated to be in the therapeutic range. CONCLUSIONS: These results demonstrate a dual action of luminally applied endothelin-1 in human resistance vessels in vivo, consisting of transient initial vasodilation followed by pronounced vasoconstriction, and suggest that blockade of voltage-operated calcium channels can effectively counter the vasoconstrictor effects of endothelin-1. PMID- 8207562 TI - Endothelin-releasing stimuli and calcium antagonists in normal and pathological conditions. AB - BACKGROUND: Endothelin-1 is a potent vasoconstrictive peptide which circulates in blood at very low concentrations. It is mostly released from endothelial cells towards the vascular smooth muscle cells. Therefore studies addressed at increasing endothelin-1 production using physical stimuli may easily fail to cause sizeable modifications in plasma endothelin levels. Upright posture and exposure to cold, the two maneuvers so far most commonly used in humans, often have inconsistent effects on plasma endothelin-1. RECENT FINDINGS: In recent studies we have found that exposure to high altitude (4500-5000 m) caused, in normal subjects, significant increases in endothelin-1 which were correlated with those of mean arterial pressure and of systolic pulmonary pressure. CONCLUSIONS: Hypobaric hypoxia appears to stimulate the secretion of endothelin-1 and this response may contribute to the adaptation by the systemic and pulmonary circulation to the stress of altitude. If this can be confirmed, calcium antagonists, which are known to antagonize endothelin-1 mediated vasoconstriction, may be used to alleviate the pulmonary hypertension that occasionally occurs under these specific circumstances. PMID- 8207564 TI - Small arteries and hypertension. AB - AIM: To review current knowledge on the behaviour of small arteries in hypertension and when the blood pressure is lowered. METHOD: Literature review. CONCLUSIONS: The evidence available at present suggests that despite normalization of blood pressure, the flow reserve in small coronary arteries is not necessarily restored to normal. Therefore the risk of cardiac ischaemia may remain and this may explain the current failure to reduce all cardiac risk associated with hypertension despite effective antihypertensive treatment. PMID- 8207563 TI - Calciotropic hormones in salt-sensitive essential hypertension: 1,25 dihydroxyvitamin D and parathyroid hypertensive factor. AB - HYPOTHESIS: Some, but not all, men and women display a pressor response to increases in dietary salt intake. The mechanism(s) underlying this salt-sensitive hypertension remains poorly defined. We have developed a hypothesis that all hypertension arises from an imbalance between mechanisms of cytosolic calcium accumulation from the extracellular space versus calcium release into the cytoplasm from intracellular storage sites. Extracellular calcium-dependent hypertension predominates in salt-sensitive subjects, while excess angiotensin II mediates the excess intracellular calcium release that is characteristic of renin dependent salt-insensitive forms of hypertension. Studies on pressor hormones: We investigated potential etiologic factors mediating the cellular calcium accumulation in salt-sensitive hypertensive human subjects, and focused on two calcium-related circulating hormonal substances, 1,25-dihydroxyvitamin D and the recently described parathyroid hypertensive factor. Both of these substances directly facilitate calcium transport from the extracellular space in the cell. Furthermore, levels of these hormones are greatest in black normotensive and low renin essential hypertensive subjects, both groups associated with salt-related hypertensive disease. Lastly, dietary salt loading elevates 1,25-dihydroxyvitamin D and parathyroid hypertensive factor levels, and the greater the level of either hormone, the greater the pressor response to salt. CONCLUSIONS: It is reasonable to consider that these salt-induced cellular ionophoric actions of 1,25 dihydroxyvitamin D and parathyroid hypertensive factor contribute, at least in part, to the mechanism of salt-sensitive hypertension in man. PMID- 8207565 TI - Scaphoid fracture as a "puncher's fracture". AB - We investigated 18 scaphoid fractures induced by punching. The wrist position while punching was neutral to slight palmar flexion. We postulated that the mechanism of the fracture was caused by the concentration of the external force to the second metacarpus. The forces are then dispersed to the trapezium and trapezoid, which produces shear stress at the waist of the scaphoid. In spite of the differences in mechanism, the location of the fracture was similar to fractured scaphoids caused by wrist extension injuries. Regardless of the wrist positions, the carpal scaphoid is most vulnerable to fracture due to its characteristic morphology. PMID- 8207566 TI - Production of a standard closed fracture in the rat tibia. AB - In order to develop a technique for producing a standard closed transverse fracture in the rat tibia, the method of Bonnarens and Einhorn was modified and tested on 176 tibiae. A 0.9-mm Kirschner wire was inserted percutaneously near the tibial tuberosity into the intramedullary canal, and a tibial fracture was created at the junction of the middle and distal third of the tibia with a blunt guillotine driven by a dropped weight. Radiographs confirmed the production of a highly reproducible transverse mid-shaft tibia fracture in 90% of the fractures. Minimal comminution of the fracture or angulation of the Kirschner wires resulted. The Kirschner wires were removed without difficulty after the rats were put to death and did not disturb the fracture site. Mechanical testing and histological studies showed that a standard fracture healing process was obtained by using this method. The results indicate that this modified method creates a standard, reproducible transverse closed fracture of rat tibia. PMID- 8207567 TI - Save the trees: a comparative review of skier-tree collisions. AB - From 1981 to 1989, 323 patients whose diagnoses resulted from ski injuries were emergently admitted to a Class 1 Trauma Hospital. Of this group, 107 (33%) were injured in skier-tree collisions. This tree collision group (TC group) was compared with a group that did not hit a tree (non-tree-collision group or NTC group). The average age of the TC group was 26 years, compared with 31 years in the NTC group. The Revised Trauma Score (RTS) was recorded for each patient. The TC group's average trauma score was 7.205, compared with 7.7395 for the NTC group. The Injury Severity Score (ISS) was also recorded. The TC group's ISS averaged 14.7, compared with 9.1 for the NTC group. Both of these scores demonstrated statistical significance. Certain injuries such as skull fractures, head injuries, pelvic fractures, and chest injuries (including rib fractures, pneumothoraces, and pulmonary contusions) were more common in the TC group. Tibia fractures were more common in the NTC group. Femur fractures and upper extremity fractures were evenly distributed between the two groups. Seven deaths were recorded in the TC group and five deaths occurred in the NTC group. PMID- 8207568 TI - Comparison of the Howmedica and Synthes military external fixation frames. AB - To direct the U.S. military purchase of deployable external fixation gear, a project was designed to compare the biomechanical properties and ease of clinical application of military external fixators developed by Synthes and Howmedica. The project assessed (a) ease of application, (b) biomechanics, (c) heat stability, and (d) product line compatibility. Pretrained general surgery residents were provided with fresh cadaver limbs with simulated grade IIIB tibial fractures and 5-cm middiaphyseal defects. All chose the Howmedica Ultra-X for its ease of application but, on manual testing, noted that the Synthes Trauma-Fix was more stable. The frames were biomechanically tested in a previously validated model with strictly controlled parameters. The Howmedica Ultra-X demonstrated only 75% of the compressive stiffness, 29% of the anteroposterior bending stiffness, and 51% of the torsional stiffness of the Synthes Trauma-Fix. The Ultra-X failed to withstand steam sterilization and was significantly weaker than, and incompatible with, Howmedica's commercially available product. The Trauma-Fix demonstrated no statistically significant difference from Synthes' commercially available product. The Howmedica Ultra-X is unsuitable for military external fixation: The biomechanical properties are not equivalent to those of the unilateral Hoffmann frame, it is incompatible with commercially available Howmedica external fixators, and it fails to withstand heat sterilization. PMID- 8207569 TI - SSEP monitoring during pelvic and acetabular fracture surgery. AB - Forty-one consecutive patients requiring surgery for pelvic or acetabular fractures were reviewed to compare the 20 patients (20 fractures) who had SSEP monitoring to the twenty-one patients (22 fractures) in whom monitoring was not available. In the unmonitored group, five patients had a preoperative neurologic deficit (three major/two minor), whereas in the monitored group there were nine patients with deficits (two major/seven minor). Intraoperatively, significant somatosensory evoked potential (SSEP) changes occurred in six of the monitored patients. In five patients the changes resolved on correction of the offending action and there was no postoperative deficit. In the remaining case, SSEP changes did not resolve and the patient awoke with a peroneal palsy. This one monitored patient with a new deficit compares with five patients with postoperative new deficits (or deteriorations) in the unmonitored group. The majority of intraoperative SSEP changes and iatrogenic deficits occurred during surgery through the ilioinguinal approach. During follow-up, the great majority of deficits resolved completely or had significant improvement. PMID- 8207570 TI - Immediate interlocking nailing of fractures of the femur caused by low- to mid velocity gunshots. AB - A retrospective review of 39 fractures of the femur in 37 patients caused by low- and mid-velocity handgun missiles treated with static interlocking nailing within 18 h of injury was conducted to evaluate the efficacy, safety, and cost savings of immediate intramedullary nailing in these injuries. Patients were followed through union of the fracture with an average follow-up of 12.5 months. The average hospitalization was 8.5 days. All but two fractures healed in an average of 14 weeks (range 8-28). One delayed union was treated with exchange intramedullary nailing with reaming 5 months postinjury and progressed uneventfully to fracture union. One nonunion occurred, presenting with broken distal interlocking screws 18 months after injury, which was treated with an exchange intramedullary nailing with reaming. The nonunion healed within 4 months of this secondary procedure. There were no malunions of > 5 degrees angulation, no leg length discrepancies of > 1.0 cm, and no rotational malalignments noted. There was one (2.5%) infection that was successfully treated with nail removal, reaming of the canal, and reinsertion of a larger diameter nail. We conclude that immediate interlocking nailing of low- and mid-velocity gunshot fractures of the femur is an effective and safe treatment. Compared with previously published data on intramedullary nailing of femoral gunshot fractures, immediate intramedullary nailing resulted in a shorter hospital stay with a significant decrease in hospital expenses. Because the findings of this study indicate that early fixation in these injuries had no detrimental effect on the clinical results, we recommend immediate intramedullary nailing of gunshot fractures of the femur. PMID- 8207571 TI - Long term results of unicondylar fractures of the femur. AB - Twenty-four unicondylar fractures of the distal femur were treated at the Trauma Center "Bergmannsheil," University of Bochum, Germany, between 1981 and 1990. All patients sustained their injuries from severe direct trauma. There were 16 lateral condylar fractures, five medial condylar fractures, and three tangential posterior ("Hoffa-type") fractures. Twenty-three closed injuries and one grade IIIB open fracture are included. Nine patients (37.5%) sustained concomitant injuries to the skeleton. All fractures were treated with open reduction and internal fixation with screws within 8 h of admission. Postoperative management consisted of early continuous passive motion and minimal weight bearing for 6-8 weeks progressing to full weight bearing. The mean follow-up was 62 months (24 120). The therapeutic outcome (clinical result, radiographs) was rated by the Neer score. Twenty patients were rated excellent, three achieved satisfactory results, and one had an unsatisfactory result. All patients without an excellent outcome had accompanying injuries. Open reduction and internal screw fixation of unicondylar femur fractures provides overall excellent long-term results. The therapeutic outcome is significantly affected by associated injuries of the skeleton. PMID- 8207572 TI - Evaluation of methods of internal fixation of transverse patella fractures: a biomechanical study. AB - Biomechanical testing was performed to evaluate five techniques of internal fixation of transverse patella fractures. Using cadaveric lower extremities, transverse osteotomies of the patella were performed, and the simulated fractures were fixed with the following techniques: the modified tension band, anterior tension band with a supplemental cerclage wire (the Pyrford technique), tension band with cancellous bone screws, Pyrford technique with cancellous screws, and cancellous screws alone. The fixation techniques were evaluated by measuring the separation of the fracture fragments during loading to produce a physiologic range of motion (90 degrees flexion to full extension). All techniques functioned adequately, with no fracture gap exceeding 1 mm. The tension band with screws technique performed significantly better than did the modified tension band, with an average fracture gap approximately half that of the traditional modified tension band technique. Mechanically, the addition of the screws to the tension band techniques reduces fracture separation by providing compression throughout the range of motion and by resisting the tensile loading during terminal extension. PMID- 8207573 TI - Tibia fractures produced from the impact of a baseball bat. AB - Forty-seven patients presented during a 1-year period with fractures of the extremities produced by the impact of a baseball bat. This represented an increase of fourfold in fractures associated with baseball bat trauma as compared with the previous year. Those patients with tibia fractures were retrospectively reviewed in terms of associated soft-tissue injuries, fracture pattern, and fracture healing. Potential force generated and kinetic energy transferred when a baseball bat strikes the tibia were calculated mathematically to provide correlation with clinical observations. Tibia fractures produced by baseball bats represented 10% of all tibia fractures presenting from July 1990-July 1991. Of these 11 tibia fractures, 3 developed compartment syndrome, necessitating fasciotomy and subsequent skin grafting, and 1 developed osteomyelitis, which eventually resulted in amputation. One patient had superficial skin blistering that required a delay in definitive fracture care of 11 days and subsequent skin grafting. There was one nonunion and three delayed unions requiring additional operative intervention. This incidence of compartment syndrome (27%) is nine times higher than the overall incidence, at this institution, of compartment syndrome (3%) in tibia fractures produced by other mechanisms. The maximum potential kinetic energy produced during the impact of a baseball bat is 515 kg/m2/s2: 25% higher than that produced by a 9-mm bullet fired at a distance of 6 ft (407 kg/m2/s2). The potential force transmitted from a bat to the tibia at the time of collision is 8,000 lb, three times that of the bullet (626 lb).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207574 TI - Intraarticular contact stresses with simulated ankle malunions. AB - Peak contact stresses were evaluated in a human cadaver ankle model of ankle fracture malunion. In one set of experiments, changes in peak contact stresses were evaluated for ankles loaded with lateral displacements of the talus and fibula of 1, 2, 3, and 4 mm. In a second set of experiments, peak contact stresses were evaluated after removal of posterior malleolar fragments. Peak contact stresses were concentrated over the anterior medial talar dome in normal specimens, and in specimens with stimulated malunions. There were relatively low stresses beneath the medial malleolus. Peak stresses for ankles without talar displacements ranged from 1.9 MPa to 12.4 MPa (eliminating one disparate specimen). There was no increase in peak stresses with lateral displacements of the talus or with removal of posterior malleolar fragments. The fact that peak stresses with simulated ankle malunions were not elevated suggests that factors other than the magnitude of normal contact stresses are of greater importance in the pathogenesis of posttraumatic arthritis. PMID- 8207575 TI - Ankle dislocation. AB - From 1980 to 1991, 14 patients with pure ankle dislocation unassociated with fracture were identified. All patients were young adults (18-41 years of age) with a male preponderance (11 of 14). The cause of injury in nine of the 14 cases was a motor vehicle accident and in the remainder, sporting events or fall from a height. Thirteen of the 14 injuries were open, and 12 patients underwent lateral ligamentous repair. Twelve of the 14 patients were available for follow-up, which ranged from 15 to 122 months. Two patients had poor results; the remainder (10 of 12) had good and excellent results. Interestingly, no patient had signs or symptoms of instability. One patient required immediate below-the-knee amputation for open dislocation associated with avulsion of soft tissue and neurovascular structures. PMID- 8207576 TI - The pulmonary artery catheter: a diagnostic adjunct for fat embolism syndrome. AB - Available objective tests for fat embolism are neither sensitive nor specific. We performed frozen-section analysis of blood aspirated from a pulmonary artery catheter in a trauma victim with fat embolism syndrome and found marked levels of pulmonary microvascular blood fat. The amount of fat detected in this patient with long bone fractures was higher than that observed in a pilot study of this technique in cardiopulmonary bypass patients. This technique provided diagnostic support of our clinical findings. The procedure may prove useful in patients with an equivocal diagnosis of fat embolism or when the cause of posttraumatic acute pulmonary insufficiency is unknown. PMID- 8207577 TI - Ipsilateral hip and knee dislocation. AB - Hip and knee dislocations individually are two of the relatively limited orthopaedic emergencies. Long-term results of treatment of these two types of injury are associated with avascular necrosis of the femoral head, knee instability, and knee stiffness. Correct early diagnosis, including arteriography in the case of knee dislocation, is crucial. Prompt treatment consisting of closed or open reduction of the dislocations is necessary. Additional treatment involving knee ligament reconstruction is warranted to maximize knee function in healthy, active patients. Simultaneous occurrence of ipsilateral hip and knee dislocations is a particularly morbid injury. We report such a case to emphasize that early, aggressive treatment and extensive physical therapy can result in a functional and painless lower extremity. PMID- 8207578 TI - A modified technique for removing a bent intramedullary nail minimizing bone and soft tissue dissection. PMID- 8207579 TI - Severe open fractures of the lower extremity: a retrospective evaluation of the Mangled Extremity Severity Score (MESS) AB - Recent reports using the Mangled Extremity Severity Score (MESS) suggest that a score of > or = 7 is 100% accurate in predicting the need for amputation of severely injured lower extremities. To further evaluate the value of the MESS in predicting amputation, specifically with respect to type IIIB and type IIIC (Gustilo and Anderson) open fractures of the tibia, we retrospectively evaluated 24 patients with these injuries. A significant difference (p = 0.001) between MESS values of 13 salvaged (6.36 +/- 0.35 SEM) and 11 amputated limbs (6.36 +/- 0.54 SEM) was found. A MESS value of > or = 4 was most sensitive (100%); a MESS value of > or = 7 was most specific, and a MESS value of > or = 7 was found to have a positive predictive value of 100%. Subsequently, we addressed recent criticisms of the MESS by including nerve injury in the scoring system and by separating soft-tissue and skeletal injury components of the MESS. We modified the MESS with a score called the NISSSA and applied it retrospectively to our cases. After careful statistical comparison we found both the MESS and NISSSA to be highly accurate (p < 0.005) in predicting amputation. The NISSSA was found to be more sensitive (81.8% versus 63.6%) and more specific (92.3 versus 69.2%). PMID- 8207580 TI - Midshaft clavicle nonunions treated with intramedullary Steinman pin fixation and onlay bone graft. AB - The current literature tends to favor rigid internal fixation with plates for symptomatic midclavicular nonunions. From 1985 to 1992, 14 patients with clavicular nonunions were treated by open reduction and intramedullary Steinman pin fixation with onlay iliac crest bone grafting. The average age of patients was 36 years (range 18-62). The majority of nonunions occurred after high-energy injuries to the clavicle. Three patients had failed previous plating and one initial fracture was pathological through irradiated bone. At an average follow up of 4 years, all nonunions healed uneventfully and all were satisfied with the result of surgery. There were no infections or pin migrations. All hardware was removed at an average of 12.7 weeks (7-24 weeks). The most significant complications were two refractures occurring through osteopenic bone. We have found this technique to be as effective as plating procedures, yet it maintains the great advantage of ease of hardware removal. It allows early motion and has been useful in those whose previous plating procedures have failed. PMID- 8207581 TI - Treatment of radial head fractures with absorbable polyglycolide pins: a study on the security of the fixation in 38 cases. AB - Between 1986 and 1992, 43 patients with a displaced Mason type II or type III fracture of the radial head were treated by open reduction and internal fixation using absorbable polyglycolide pins. Five patients were lost to the follow-up. The clinical results were reviewed in 38 patients with an average follow-up time of 27 months. There were 19 type II and 19 type III fractures. The functional results were excellent or good in 36 patients (95%). A postoperative redisplacement was seen in one patient. Use of absorbable polyglycolide pins appear to be a feasible alternative method for the treatment of displaced radial head fractures. The results were at least equal to those obtained with metallic implants, but absorbable devices need not be removed. A complication unique to the absorbable devices is a transient local abacterial tissue reaction. The rate of tissue reaction has decreased lately, and in this study no adverse reactions from the implants occurred. PMID- 8207582 TI - The floating radius in bipolar fracture-dislocation of the forearm. AB - Ten cases of bipolar forearm fracture-dislocation are presented. Recognition of the full extent of the skeletal, articular, and soft-tissue injuries is essential. Treatment consists of an anatomical reduction and proximal and distal stabilization of the skeleton to achieve control as well as maintain the position of the floating radius segment. The forearm bones can then be maintained in an optimal position to avoid interosseous soft-tissue contracture that will compromise the supination-pronation function of the forearm. PMID- 8207583 TI - Effects of transforming growth factor-beta 1 and fibroblast growth factor on DNA synthesis in growth plate chondrocytes are enhanced by insulin-like growth factor I. AB - The local tissue metabolism is controlled through the complex interaction between systemic and local growth factors. In recent years, an increasing number of autocrine or paracrine growth regulators have been identified in physeal cartilage. While these factors act to alter chondrocytes phenotypically and presumably are important mediators in the process of endochondral ossification, the manner in which they interact with the systemically regulated growth factor insulin-like growth factor-I is unknown. In the present study, the interactive effects of insulin-like growth factor-I with transforming growth factor-beta 1 or basic fibroblast growth factor were examined in short-term monolayer cultures of chick growth plate chondrocytes. [3H]thymidine incorporation was maximally stimulated 11-fold by fibroblast growth factor (10 ng/ml) and 3.5-fold by transforming growth factor-beta 1 following a 24-hour exposure in serum containing cultures. The effects of transforming growth factor-beta 1 and fibroblast growth factor at both high and low concentrations were enhanced in a dose-dependent manner by insulin-like growth factor-I, with a 40-50% increase in DNA synthesis in the presence of 100 ng/ml of insulin-like growth factor-I. Since insulin-like growth factor-I increased [3H]thymidine incorporation after 48 hours (50% increase) but not after 24 hours of exposure, these observations represent a synergistic interaction. Total DNA in cultures treated for 5 days confirmed the modulating effect of insulin-like growth factor-I with transforming growth factor beta 1 and fibroblast growth factor. The growth factors were further examined for their effects on markers of chondrocyte differentiation. While all three caused a dose-dependent inhibition of alkaline phosphatase activity, the effects of insulin-like growth factor-I were additive only to those of transforming growth factor-beta 1 and fibroblast growth factor. Similarly, insulin-like growth factor I did not affect the sulfate incorporation stimulated by fibroblast growth factor or transforming growth factor-beta 1. Insulin-like growth factor-I had no effect on total protein synthesis after 24 hours and, although type-II collagen mRNA levels were stimulated, it had no effect on type-X collagen mRNA, as determined by quantitative in situ hybridization. Finally, insulin-like growth factor-I did not alter the dose-dependent stimulation of noncollagen protein synthesis and the inhibition of collagen synthesis caused by fibroblast growth factor and transforming growth factor-beta 1 in 24-hour cultures. Thus, the data suggest that insulin-like growth factor-I may have a role in augmenting the effects of other growth factors found in cartilage.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8207584 TI - Chondrocyte cells respond mechanically to compressive loads. AB - Many studies have illustrated the effect of mechanical loading on articular cartilage and the corresponding changes in chondrocyte metabolism, yet the mechanism through which the cells respond to loading still is unclear. The purpose of this study was to evaluate the change in shape of chondrocytes under a statically applied uniaxial compressive load. Isolated chondrocytes from rat chondrosarcoma were embedded in 2% agarose gel. Strains of 5, 10, and 15% were applied, and images of the cell were recorded from initial loading to equilibrium (15 minutes). A finite-element model was used to model the experimental setup and to estimate the mechanical properties of the chondrocyte at equilibrium. The transient behavior of the composite in the experiment was analyzed with use of a standard linear viscoelastic model. We found that all cells decreased in cross sectional area under each of the applied compressive strains. In the finite element model, the elasticity of the chondrocyte was similar to that of the surrounding agarose gel (4.0 kPa) and had a Poisson's ratio of 0.4. Viscoelastic analysis showed that the chondrocytes contributed a significant viscoelastic component to the behavior of the composite in comparison with the agarose gel alone. If a decrease in cell volume proportional to the decrease in cross sectional area is assumed, the decrease observed was greater than would be predicted by a passive cellular response due to an equivalent osmotic pressure. This indicates that the chondrocyte may be altering its intracellular composition by cellular processes in response to mechanical loading. PMID- 8207585 TI - Effect of animal age and chronicity of interleukin-1 exposure on cartilage proteoglycan depletion in vivo. AB - Rheumatoid arthritis and osteoarthritis are characterized by an early depletion of cartilage proteoglycans, which leads to a decrease in cartilage compressibility and, eventually, to a loss of joint function. Interleukin-1, which is thought to have a role in mediating this loss of proteoglycans in arthritis, induces an acute depletion of proteoglycans from articular cartilage following intra-articular injection in rabbits. As the structure and metabolism of proteoglycans are known to change with age, my laboratory investigated the effect of age on depletion and recovery of proteoglycans in response to interleukin-1 in the rabbit. Loss of cartilage proteoglycans induced by interleukin-1 was less severe in immature animals, increased until the age of sexual maturity, and then remained constant. The rate of recovery and compensatory overshoot in the rate of proteoglycan synthesis following challenge with interleukin-1 was more rapid in immature animals and may have been responsible for the quicker return of the cartilage proteoglycan content to control levels in younger animals. With multiple exposures to interleukin-1 at time intervals too short for recovery to occur, smaller amounts of interleukin-1 induced loss of proteoglycans, and the proteoglycan content and the rate of synthesis remained depressed longer after treatment had stopped. The decreased ability of mature cartilage to replace proteoglycans rapidly after exposure to cytokines would increase the probability of subsequent inflammatory episodes before recovery is complete; this may result in increased susceptibility of adult cartilage to proteoglycan depletion. PMID- 8207586 TI - Osteoarthritis in cynomolgus macaques: a primate model of naturally occurring disease. AB - The objective of the present study was to determine if naturally occurring osteoarthritis of the knee joints that is similar to the condition in humans develops in cynomolgus macaques. Knee joints from 58 young adult (mean age, 7.4 years) female cynomolgus macaques were studied with x-ray densitometry, high detail radiography, and histology. The animals studied were subjects in a triad designed to examine the effects of the administration of sex steroids on atherosclerosis; except for a control group, the monkeys had been either ovariectomized or treated with sex steroids for 2 years. Therefore, the data were analyzed to determine if these treatments, both of which can influence bone density, affected the severity of osteoarthritis. There was a high prevalence of osteoarthritic lesions, morphologically similar to those seen in humans. Bone changes were more common and severe than cartilage changes and morphologically appeared to precede the cartilage changes. Treatment with testosterone resulted in increased body weight, body mass index, and bone mineral content in the femur and tibia but did not affect the severity of osteoarthritis. These data indicate that naturally occurring osteoarthritis developed in the knee joints of cynomolgus macaques; these animals may be a useful model for the study of osteoarthritis in humans. PMID- 8207587 TI - Comparative study of the intrinsic mechanical properties of the human acetabular and femoral head cartilage. AB - Biphasic creep indentation methodology and an automated indentation apparatus were used to measure the aggregate modulus, Poisson's ratio, permeability, thickness, creep and recovery equilibrium times, and percentage of recovery of normal articular cartilage in 10 human hip joints. These properties were mapped regionally to examine the mechanical factors involved in the development of site specific degenerative lesions in the acetabulum and femoral head. The results indicate that there are significant differences between these properties regionally in the acetabulum and femoral head and between the two anatomical structures. Specifically, it was found that cartilage in the superomedial aspect of the femoral head has a 41% larger aggregate modulus than its anatomically corresponding articulating surface in the acetabulum. In addition, the superomedial aspect of the femoral head has the greatest aggregate modulus (1.816 MPa) within the hip joint. During sitting, the inferior portion of the femoral head is in contact with the anterior acetabulum, and the anterior acetabulum has a 53% greater aggregate modulus than the inferior femoral head. This area below the fovea on the femoral head has the least aggregate modulus (0.814 MPa) within the hip joint. These mismatches in the compressive modulus of opposing articulating surfaces may contribute to degeneration of cartilage in the superomedial acetabulum and the inferior femoral head. Our findings support the clinical observation that these areas are frequent sites of early degeneration. PMID- 8207588 TI - Effect of cyclic and static tensile loading on water content and solute diffusion in canine flexor tendons: an in vitro study. AB - This study was designed to determine the effects of various loading conditions (no load and static and cyclic tensile load) on the water content and pattern of nutrient diffusion of canine flexor tendons in vitro. Region D (designated by Okuda et al.) of the flexor digitorum profundus was subjected to a cyclic or static tensile load of 100 g for times ranging from 5 minutes to 24 hours. The results demonstrated a statistically significant loss of water in tendons subjected to both types of load as compared with the controls (no load). This loss appeared to progress with time. However, neither static nor cyclic loading appeared to alter the diffusion of 3H-glucose into the tendon over a 24-hour period compared with the controls. These results suggest that any benefit in tendon repair derived from intermittent passive motion is probably not a result of an increase in the diffusion of small nutrients in response to intermittent tensile load. PMID- 8207589 TI - Healing of the rabbit medial collateral ligament following an O'Donoghue triad injury: effects of anterior cruciate ligament reconstruction. AB - The effects of healing time and anterior cruciate ligament reconstruction on healing of the medial collateral ligament and stability of the knee joint were evaluated in a rabbit model of an O'Donoghue triad injury (rupture of the medial collateral ligament with removal of the anterior cruciate ligament and part of the medial meniscus). At time 0 and at 6 and 12 weeks postoperatively, the anterior-posterior translation and varus-valgus rotation of the knee, the structural properties of the femur-medial collateral ligament-tibia complex, and the mechanical properties of the substance of the medial collateral ligament were evaluated. Although anterior-posterior translation increased significantly with time, we could not demonstrate a significant temporal effect on varus-valgus rotation. The ultimate load, elongation at failure, and energy absorbed to failure improved with time. In addition, with time, failure of the complex occurred more often in the ligament substance than at the osseous insertion. Because healing time did not affect the cross-sectional area or modulus of the medial collateral ligament, the improved structural properties of the complex resulted not from improvements in the mechanical properties of the tissue but rather from healing of the tibial insertion site. By 12 weeks, the reconstructed knees had only minor signs of osteoarthrosis on the tibiofemoral surfaces; this is in contrast to the findings in anterior cruciate ligament-deficient knees in our earlier study. Additionally, at 12 weeks, the stiffness of the complexes from the reconstructed group was 1.3 times that of the anterior cruciate ligament deficient group (p < 0.05), and te ultimate load had increased by a factor of 1.6 (p < 0.05). Our findings demonstrate that reconstruction of the anterior cruciate ligament in the rabbit helps to stabilize the joint, improves healing of the medial collateral ligament, and may decrease the incidence of early-onset osteoarthrosis after an O'Donoghue triad injury. PMID- 8207590 TI - Characterization of extracellular matrix macromolecules from bovine synovial capsule. AB - Synovial capsule from the metacarpophalangeal joints of cattle was shown to be a highly collagenous tissue, with a hydroxyproline content of 100 +/- 1 micrograms/mg dry weight and a water content of 70 +/- 3.6%. Type-I collagen made up 83% of the collagen present, and the remainder was type III. When incubated in explant culture, synovial capsule incorporated [3H]acetate into both glycoproteins and hyaluronan and [3H]acetate and [35S]sulfate into proteoglycans. The rate of synthesis of proteoglycans by synovial tissue was shown to be similar to that measured for collateral ligament from the same joint. Two populations of proteoglycans were observed to be synthesized by synovial capsule. More than 90% of the 35S-labelled proteoglycans eluted with a K(av) of 0.7 on Sepharose CL-4B, and the remainder of the radiolabelled macromolecules eluted from the column with a K(av) of less than 0.5. Analysis of the major population of proteoglycans showed it to consist of a dermatan sulfate-containing proteoglycan with a core protein of 45,000 Da that had the same N-terminal amino acid sequence as decorin. PMID- 8207591 TI - Mathematical model for the mineralization of bone. AB - A mathematical model is presented for the transport and precipitation of mineral in refilling osteons. One goal of this model was to explain calcification "halos," in which the bone near the haversian canal is more highly mineralized than the more peripheral lamellae, which have been mineralizing longer. It was assumed that the precipitation rate of mineral is proportional to the difference between the local concentration of calcium ions and an equilibrium concentration and that the transport of ions is by either diffusion or some other concentration gradient-dependent process. Transport of ions was assumed to be slowed by the accumulation of mineral in the matrix along the transport path. The model also mimics bone apposition, slowing of apposition during refilling, and mineralization lag time. It was found that simple diffusion cannot account for the transport of calcium ions into mineralizing bone, because the diffusion coefficient is two orders of magnitude too low. If a more rapid concentration gradient-driven means of transport exists, the model demonstrates that osteonal geometry and variable rate of refilling work together to produce calcification halos, as well as the primary and secondary calcification effect reported in the literature. PMID- 8207592 TI - Identification of integrin receptors on cultured human bone cells. AB - The interactions of bone cells with their surrounding extracellular microenvironment may be mediated by integrins, a family of heterodimeric glycoproteins consisting of alpha and beta subunits that noncovalently interact to form cell-substratum adhesion receptors. We previously described the integrins on calvarial bone cells in rats with use of polyclonal antibodies against some integrin subunits. In the present study, we expanded this initial characterization by employing a more complete panel of monoclonal antibodies to identify integrins on human bone cells. Minced fragments of trabecular bone obtained during total knee arthroplasty were grown in culture until bone cells became confluent. The cells then were dissociated, plated again, grown to confluence, and assayed for alkaline phosphatase activity, response of cyclic adenosine monophosphate to stimulation with parathyroid hormone, and osteocalcin content. The percentage of the cells that adhered to various substrates was measured; 60-70% adhered to type-I collagen, fibronectin, vitronectin, and poly-D lysine; 40-50% adhered to type-IV collagen, laminin, and gelatin; and only 10% adhered to fibrinogen. Flow cytometric analysis with anti-integrin monoclonal antibodies and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of immunoprecipitates of the human bone cells revealed high levels of alpha 1 beta 1, alpha 3 beta 1, alpha 5, beta 1 and alpha v beta 5 integrins and much lower levels of alpha 2 beta 1, alpha 4 beta 1, alpha v beta 1, and alpha v beta 3 integrins. This description of the integrin repertoire of cultured human bone cells represents the first step toward an understanding of the role played by integrins in the growth, maintenance, and repair of bone. PMID- 8207593 TI - Effects of lathyritic drugs and lathyritic demineralized bone matrix on induced and sustained osteogenesis. AB - Demineralized bone matrix was implanted in normal and lathyritic rats. At 2 weeks, the bone that formed in the lathyritic animals had an elevated alkaline phosphatase activity and a reduced calcium content compared with the controls. Four weeks after implantation, these biochemical parameters were reversed, with a decrease in alkaline phosphatase activity and an increase in calcium content to control levels. The histology of the recovered implants revealed new bone formation. Lathyritic demineralized bone matrix was prepared from bones of rats fed beta-aminopropionitrile for 2 weeks (2-week BAPN-DBM) or 4 weeks (4-week BAPN DBM), and was implanted in normal rats. Two weeks after implantation, both preparations of lathyritic demineralized bone matrix demonstrated early bone formation, although alkaline phosphatase activity and calcium content were reduced. By 4 weeks after implantation, no biochemical or histological evidence of bone formation remained at the site of the 4-week BAPN-DBM implants; continued but reduced bone formation was observed at the site of the 2-week BAPN-DBM implants. Reconstitution of inactivated normal demineralized bone matrix with the guanidine-soluble extracts restored the osteoinductive capacity. However, reconstitution of inactivated lathyritic demineralized bone matrix (4-week BAPN DBM) failed to restore the osteoinductive capacity. These results indicate that the degree of crosslinking of the collagen matrix that acts as a carrier for osteoinductive proteins plays a key role in inducing and sustaining osteogenesis. PMID- 8207594 TI - Restoration of tissue components after insertion of absorbable fracture fixation devices of polyglycolide through the articular surface: an experimental study in the distal rabbit femur. AB - Absorbable implants for fracture fixation do not require a secondary removal procedure, a fact that could make them particularly suitable for intra-articular fixation, provided the degree of regeneration of the articular surface is acceptable. To determine the restoration pattern in distal rabbit femurs after the intra-articular insertion of absorbable fixation devices, polyglycolide pins and screws were implanted through the articular surface of the intercondylar portion of the bone in adult animals. The polymer was known to have a degradation time of approximately 20 weeks. At follow-up times of 3-48 weeks, the restoration of the tissue components was examined histomorphometrically and microradiographically. The intact contralateral femur served as an internal control. The first signs of degradation of the implants were seen at 6 weeks. The mean fractional osteoid formation surface of the bone trabeculae within the sample fields showed significantly increased values until 6 weeks but thereafter approached the level of the control femur. In the 36-week and 48-week specimens, the polyglycolide had been absorbed and the intra-articular entrance of the implant channel had become filled either with firm whitish tissue resembling mature articular cartilage or with soft undifferentiated mesenchymal tissue only. Good restoration of the trabecular bone architecture corresponding to the original subchondral bone was a prerequisite for the regeneration of the articular cartilage. The causes of the dichotomous pattern of restoration could not be identified, but possibly it represented a normal biologic variation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207595 TI - Foot inversion-eversion and knee kinematics during walking. AB - The purpose of this study was to monitor selected aspects of the three dimensional kinematics of the knee during walking with regular shoes and with modified shoes that induced either pronation or supination of the foot. Steinmann traction pins were inserted into the right tibia and femur of five adult men who had apparently normal lower extremities. Target clusters mounted onto the pins were filmed by four cine cameras operating at 100 frames/sec. Two trials per subject were analyzed for each of the three experimental conditions: regular running shoes, running shoes with a 10 degree valgus wedge, and running shoes with a 10 degree varus wedge. The different types of footwear induced only minor kinematic changes at the knee during the stance phase of walking. The angular patterns of the tibiofemoral joint were modified by less than 1 degree, whereas the translatory patterns were altered by 2 mm. Immediately following foot-strike, the valgus-wedge shoes caused the tibia to rotate internally 4 degrees more than the varus-wedge shoes, but at the tibiofemoral joint no consistent differences in the pattern of internal-external rotation between normal and modified footwear were measureable. These findings suggest that, in the healthy lower extremity, increased internal and external tibial rotation is resolved at the hip joint, with changes at the tibiofemoral joint that barely are detectable with the techniques used in this study. PMID- 8207596 TI - Technique for in vivo measurement of the three-dimensional kinematics and laxity characteristics of the ankle joint complex. AB - We introduce here a technique to measure the three-dimensional kinematics and laxity characteristics of the ankle joint complex in vivo. The system consists of an optoelectric, kinematic data acquisition system that is used to measure the motion of the ankle joint complex in response to controlled moments applied through a system of pneumatic actuators. As a first step toward development of the method into a quantitative diagnostic tool for injuries of ankle ligaments, we addressed the following questions: (a) What is the reliability for measurement of range of motion and laxity of the ankle joint complex? (b) Are there significant differences in laxity between the left and right joints of a healthy individual? and (c) Are there significant differences in laxity of the ankle joint complex between men and women? To answer these questions, we performed repeated measures of range of motion and laxity of paired ankles in a population of 18 healthy young individuals. The high intraclass correlation coefficients obtained from the statistical analysis indicate that the new experimental system is highly reliable in measurement of total range of motion and total laxity of the ankle joint complex. We further concluded that, within the statistical power available in our experimental design, there are no significant differences in either range of motion or laxity between left and right ankles of healthy individuals or between men and women. PMID- 8207597 TI - Role of fibronectin in staphylococcal adhesion to metallic surfaces used as models of orthopaedic devices. AB - Staphylococcal infection of various prosthetic and internal fixation devices is a major complication associated with orthopaedic surgery. This study investigated the role of the host protein fibronectin in promoting adhesion of Staphylococcus aureus and Staphylococcus epidermidis to metallic surfaces representing materials used for orthopaedic devices. Pure human fibronectin was adsorbed in vitro onto coverslips (0.8 x 0.8 cm) of stainless steel, pure titanium, or titanium-aluminum niobium alloy. In vitro bacterial adhesion was promoted more strongly by the metallic surfaces coated with fibronectin than by albumin-coated controls for two strains of S. aureus and one strain of S. epidermidis. Furthermore, with the fibronectin-coated coverslips, bacterial adhesion to titanium alloy was significantly greater than adhesion to stainless steel. Adhesion of the three staphylococcal strains was promoted more strongly by coverslips explanted from the subcutaneous space of guinea pigs and tested under similar conditions than by albumin-coated controls. Incubation of either in vitro fibronectin-coated or explanted metallic coverslips with anti-fibronectin antibodies produced a significant decrease in staphylococcal adhesion. These results suggest that the presence of fibronectin on the surface of implanted metallic devices is an important determinant of colonization of orthopaedic biomaterials by staphylococci. PMID- 8207598 TI - Histomorphometric analysis of the repair of a segmental diaphyseal defect with ceramic and titanium fibermetal implants: effects of bone marrow. AB - We used a rat femoral diaphyseal defect/implant model to quantify the ingrowth of bone, cartilage, and fibrous connective tissue in a comparative study of woven sintered titanium fibermetal and porous hydroxyapatite/tricalcium phosphate ceramic implanted with and without the addition of syngeneic bone marrow cells. The patterns of tissue growth into the implants were analyzed with respect to time, type of implant, and the presence or absence of syngeneic marrow. Significantly more bone was found in ceramic implants than in fibermetal implants, with the addition of syngeneic marrow than without it, and at 4 months than at 2 months. Significantly more bone was found at both time periods in ceramic implants with bone marrow than in any other combination studied. We hypothesize that these findings resulted from interactions between the implanted material and its surroundings, specifically its ability to serve as a substratum for cell attachment, and cells in and around the defect, whether surgically implanted or arising from the soft-tissue bed. PMID- 8207599 TI - Scanning electron microscopic observations of the vascular structure of vertebral end-plates in rabbits. AB - We used scanning electron microscopy to examine the microcirculation in the vertebral end-plates of rabbits. The arteriola arborizes and swells at the end plate and then coils to make a microvessel loop. This loop is the structure we refer to as a vascular bud. We suggest that these loop structures of the capillaries play a major role in the nutrition of the intervertebral discs. PMID- 8207600 TI - [Four cases of olfactory neuroblastoma treated with craniofacial surgery]. AB - We report 4 cases of olfactory neuroblastoma with anterior cranial fossa extension treated by craniofacial surgery. Three patients have been alive and well for 4 years, 1 year and 11 months after the initial treatment without major surgical complications but one patient died of local recurrence 11 months after treatment. Multidisciplinary surgery for olfactory neuroblastoma with intracranial extension permits radical tumor excision and reconstruction of the anterior skull base. This one-stage procedure combining neurosurgery and plastic surgery with pre or post-operative radiotherapy is considered to be essential for eradicating this tumor. PMID- 8207601 TI - [Intracordal injection therapy using atelocollagen for unilateral laryngeal paralysis under local anesthesia]. AB - Intracordal injection therapy is a surgical therapeutic modality for glottic incompetence caused by unilateral laryngeal paralysis. Atelocollagen, which has recently been attracting attention as a material for use in intracordal injection therapy that supplants silicon, was initially claimed and expected, by virtue of its salient biophysical properties, not to cause impaired wave-motion of the vocal mucosa when injected into the submucosa. Unfortunately, however, our attempt to use this material for the same purpose proved disappointingly unsuccessful, with vocal sounds produced thereafter being metallic, vocal folds becoming tense and consequently transforming the site into a muscular coat of vocal muscles. During the past 3 years, we at the Department of Otolaryngology of the Jikei University School of Medicine, have performed intracordal injection therapy with atelocollagen on 20 patients diagnosed as having unilateral laryngeal paralysis under local anesthesia using a flexible fiberscope and a stroboscope under a video monitoring system. Comparisons were made of the voice before and after injection in 6 patients receiving submucosal injection and 14 given intramuscular injection of the material. In some autopsied patients, histological findings of the treated vocal cords were scrutinized and problems regarding atelocollagen injection were investigated. Judging from pathological findings of the vocal cords after atelocollagen injection and the clinical results of this therapeutic procedure, it seems most appropriate to inject this plastic material into the vocal muscles. This will prevent atelocollagen diffusion and maintain unimpaired wave-motion of the vocal mucosa, thus resulting in an acceptable voice quality. PMID- 8207603 TI - [Detection of Epstein-Barr virus-1,2 in malignant head and neck tumors by newly developed polymerase chain reaction method]. AB - The polymerase chain reaction method (PCR) was employed for the analysis of EBV genotypes in nasopharyngeal carcinoma, malignant lymphoma of head and neck origin and infectious mononucleosis. In nasopharyngeal carcinoma, type 1 EBV was detected in 12 cases and type 2 in one. Type 1 EBV was also detected in 3 out of 8 malignant lymphoma and 2 infectious mononucleosis. These results indicate that type 1 EBV is strongly predominant in nasopharyngeal carcinoma and predominant in malignant lymphoma and infectious mononucleosis. Our results may reflect the general prevalence of these two types of EBV in Japan, as we previously reported. PMID- 8207602 TI - [Development of a polymerase chain reaction (PCR) system for detection of Epstein Barr virus 1,2--application to various tonsillar disorders]. AB - A one-step PCR system was developed for detection of two types of EBV, using a single pair of primers that were complementary to both sequences coding the EBV nuclear antigen (EBNA)-2, and encompassing a large deletion in the sequence of type 1 EBV. Type 1 and type 2 EBV were detected simultaneously by polyacrylamide gel electrophoresis and ethidium bromide stains after amplification. The specificity of amplification was confirmed by Southern blot hybridization with the oligonucleotide probe that was complementary to both EBNA-2 regions. Additionally, two pairs of type specific primers were synthesized from divergent sequences in the EBNA-2 regions of type 1 and type 2 EBV. The PCRs were employed for analysis of the EBV genotype in the oral cavities of healthy donors and patients with various tonsillar disorders. EBV was detected in 60 samples from healthy donors and patients with various tonsillar disorders. Fifty-six contained type 1 and four type 2. Double infection was not seen in either healthy donors or patients. These results indicate that type 1 EBV is highly dominant in Japan. It is interesting to note that patients with acute tonsillitis and palmoplantar pustulosis showed a statistically higher frequency (P < 0.01) of EBV excretion than healthy donors. In examining anti-EBV viral capsid (VCA)-IgG antibody titers and EBV excretion in the oral cavity, EBV excretion was not found to correlate with the VCA-IgG antibody titers. PMID- 8207604 TI - [Serum antibodies to type II collagen and immune complex in cases of Meniere's disease]. AB - In a previous study, endolymphatic hydrops was induced in 36% of guinea pigs immunized with type II collagen and a dominant negative SP was recorded from these hydropic animals. These results suggested that the immune response to type II collagen may have a role in the etiopathology of some cases of Meniere's disease. In this study, we evaluated the levels of serum antibody to type II collagen and three other immune indexes in patients with Meniere's disease, especially those who showed negative SP dominance on electrocochleography. Twenty nine Meniere's cases, 22 normal volunteers serving as controls, 28 RA cases, and 9 patients complaining of vertigo were examined to detect serum immune indexes. Meniere's patients exhibited high values of serum anti-type II collagen antibody as compared to control subjects. Furthermore, total IgG, C3, anti-type II collagen antibody and circulating immune complex were increased with the highest levels being in the RA group, followed by Meniere's disease and then the control group. These results probably reflect the extent of immune reaction development. The immune response may be generalized in RA cases and/or local in Meniere's disease. Our study results suggest the development of certain immune status abnormalities in our cases, which lends support to the idea of an immunologic disorder playing a role in the etiology of some cases of Meniere's disease. PMID- 8207605 TI - [The effect of aging on middle ear dynamic characteristics]. AB - The effect of aging on middle ear function has not been investigated thoroughly, as there is no simple measuring apparatus except for the conventional impedance meter (IM). However, the reliability of the IM is insufficient, because the stimulus frequency is fixed and the information provided by the IM is minimal. We have developed a sweep frequency middle ear analyzer (MEA), which provides much more information on middle ear dynamic characteristics than a conventional IM, and have obtained various measurements with this device. In this paper, middle ear dynamic characteristics of 187 normal subjects (309 ears) ranging from a 4 year-old child to an elderly person, 79 years old, were measured with the MEA in the middle ear resonance frequency region where dynamic characteristics can be seen clearly, and the effect of aging on middle ear dynamic characteristics was examined. The main results obtained were as follows: Middle ear mobilities tend to increase up to the twenties, then decrease up to the forties. Subsequently, a clear difference between those of males and females is observed. The middle ear mobilities of males decrease gradually with an increase in age. In contrast, although the standard deviation values are large, those for females tend to rise with increasing age. PMID- 8207606 TI - [Influence of superior cervical ganglion stimulation of vestibular function]. AB - The sympathetic nervous system, which originates in the superior cervical ganglion (SCG) and is distributed in vestibular end organs, has been proposed to have some influence on vestibular function. The present investigation was conducted to assess the effects of unilateral electrical stimulation of the SCG, administration of a vasopressor drug, and introduction of KCl (0.7 M/ml) into the tympanic cavity on vestibular function in alert guinea pigs. Nystagmus was not observed as result of electrical irritation of the SCG (22 test animals), infusion of the KCl solution into the middle ear cavity (5 test animals), or the combination of SCG stimulation and vasopressor drug administration (7 test animals). However, when the SCG was stimulated electrically after introduction of the KCl solution into the ipsilateral cavity, nystagmus and postural deviation were observed (5 out of 12 animals). Furthermore, after the administration of a vasopressor drug to these 12 animals, irrespective of the manifestation of nystagmus, the same changes took place in response to the electrical stimulation (7 animals). These results suggest that SCB stimulation is a provocative factor for nystagmus, that infusion of KCl solution into the tympanic cavity induces a hypersensitive state in the inner ear, and that high blood pressure increases this hypersensitivity. PMID- 8207607 TI - [Inverted papillomas in the nose and paranasal sinuses]. AB - Inverted papillomas in the nose and/or paranasal sinuses exhibit a high recurrence rate, and an association with malignancy. Early diagnosis and aggressive surgical therapy are thus essential. Seventeen cases of inverted papilloma seen at Saitama Cancer Center over a 17-year period were reviewed. Common presenting symptoms, the primary papilloma sites and the results of surgical treatment were as follows. 1) Almost all patients complained of nasal obstruction. The usefulness of nasal biopsy of the tumor was confirmed, with 12 cases being diagnosed as having inverted papilloma pre-operatively. Inverted papilloma without squamous cell carcinoma caused osseous thinning, but did not destroy the bone. 2) It was found that the primary site of the papilloma involved the lateral wall of the nasal cavity. Lateral Rhinotomy was therefore recommended as a standard treatment. 3) The recurrence rate was 1/12 after Lateral Rhinotomy. Two cases had complaints associated with the Lateral Rhinotomy, nasolacrimal duct stenosis, and a scar in the median corner of eye. 4) Only one case had concomitant squamous cell carcinoma in the nose and maxillary sinus. This patient received chemo therapy, radiation therapy and finally maxillectomy, but the inverted papilloma recurred several times. Six years later, squamous cell carcinoma recurred and lead to this patient's death. PMID- 8207608 TI - Human papillomaviruses, p53, and cervical neoplasia. PMID- 8207609 TI - Cutaneous B-cell lymphoproliferative diseases: a centenary celebration classification. PMID- 8207610 TI - Measurement of nuclear DNA content in histological and cytological specimens: principles and applications. AB - Nuclear DNA content can be measured in histological and cytological material by the techniques of image and flow cytometry. The measurement depends on the availability of stoichiometric markers for DNA. Results are expressed in DNA histograms from which tumour DNA ploidy and cell proliferation status can be estimated. Flow cytometry analyses large numbers of cells and gives the most meaningful cell cycle data. Image cytometry is more specifically targeted to the population of interest and can accurately measure rare events. A large body of literature exists relating DNA cytometry to clinical outcome, but there are considerable inconsistencies between clinical series which may be due, in many instances, to problems of histogram interpretation and tumour sampling. Rapid 'user-friendly' systems currently under development may increase the clinical acceptance of DNA cytometry. PMID- 8207611 TI - Animal models of inflammatory bowel disease. PMID- 8207612 TI - Fractal geometric analysis of colorectal polyps. AB - Colorectal polyps have a subjectively self-similar structure which suggests that these structures may have fractal elements and that the fractal dimension may be a useful morphometric discriminant. The fractal dimensions of images from haematoxylin and eosin-stained sections of 359 colorectal polyps (214 tubulovillous adenomas, 41 'pure' tubular adenomas, 29 'pure' villous adenomas, 68 metaplastic polyps, and 7 inflammatory polyps) were measured using a box counting method implemented on a microcomputer-based image analysis system. Results were assessed using polychotomous logistic regression, confusion matrices, and kappa statistics. All examined polyps were shown to have a fractal structure in the range of scales examined. The fractal dimension was significantly different between different diagnostic categories (P < 0.0001) and was a useful discriminant between these categories (kappa statistic 0.60 for the confusion matrix with size as the other variable). The fractal dimension did not shown any significant correlation with the grade of epithelial dysplasia (P > 0.05). This study shows that colorectal polyps have a fractal structure over a defined range of magnification and Euclidean morphometric measurements will be invalid outside precisely defined conditions of resolution and magnification. The fractal dimension is a better way of quantitating the polyp shape and is a useful morphometric discriminant between diagnostic categories. PMID- 8207613 TI - Numerical abnormalities of chromosome 7 in human prostate cancer detected by fluorescence in situ hybridization (FISH) on paraffin-embedded tissue sections with centromere-specific DNA probes. AB - Fluorescence in situ hybridization (FISH) using chromosome-specific alpha satellite DNA probes for chromosomes 7, 8, and 12 was performed on paraffin embedded tissue sections and touch imprint preparations of 53 cases of human prostate cancer. Subsequent haematoxylin and eosin (H & E) staining of the hybridized tissue sections allowed unambiguous assignment of hybridization signals either to tumour or to non-tumorous parenchyma. Fifty-three cases of human prostate cancer were evaluated for numerical aberrations of chromosome 7. Scoring 200 cells of tumour and non-tumorous parenchyma in each case revealed abnormalities exclusively in tumour parenchyma in 41 cases (77 per cent). Ten of 41 cases (24 per cent) showed trisomy 7, and 15 cases (37 per cent) monosomy 7 or trisomy 7 in combination with monosomy 7, respectively. Sixteen cases (39 per cent) exhibited polysomy 7 in cells of the tumour parenchyma. In the tumour tissue in one case, different polyploid clones (triploid, tetraploid) and polysomy 7 could be identified by double hybridization with chromosome-specific DNA probes for chromosome 7, plus 8 or 12. The indicated numerical aberrations of chromosome 7 were correlated with 78 per cent of advanced pathological stages or poorly differentiated tumours (pT3/4 or G3) of prostate carcinomas. A statistical analysis of the data revealed significant relationships of particular numerical abnormalities of chromosome 7 to different pathological categories (pT, G, pN) of tumour classification. For the T-classification, the frequency of cells carrying polysomy 7 and polysomy 7/+7 increases significantly from pT1 to pT3/4 (P = 0.022).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207614 TI - Bcl-2 protein expression in carcinomas originating from the follicular epithelium of the thyroid gland. AB - The bcl-2 product has been related to the block of programmed cell death (apoptosis) both in lymphoid and in epithelial cells. The pathological expression of bcl-2 has been investigated mainly in haematological malignancies. Here we have investigated bcl-2 expression in a model of epithelial tumours represented by the spectrum of carcinomas arising from the follicular epithelium of the human thyroid gland. The analysis was carried out by immunocytochemistry on archival material using monoclonal antibodies against bcl-2 and thyroglobulin (Tg) on consecutive sections of 94 well-differentiated carcinomas (WDCs), 19 poorly differentiated carcinomas (PDCs), and 22 undifferentiated carcinomas (UCs) of the thyroid gland. In a subset of 5 cases of UC showing a differentiated component (UC-D), the expression of p53 protein was also investigated. As controls, fetal and adult normal thyroid glands and adenomas were analysed. bcl-2 expression was detected in 74 of 94 cases (78.7 per cent) of WDC, 16 of 19 cases (84.2 per cent) of PDC, and 3 of 22 cases (13.6 per cent) of UC. Simultaneous expression of bcl-2 protein and Tg was observed in 74 of 94 cases (78.7 per cent) of WDC, 13 of 19 cases (68.4 per cent) of PDC, and in no case of UC. bcl-2 and Tg immunostaining was detected in all fetal and normal thyroid glands as well as in the adenoma specimens examined. In the subset of UC-D, mutual exclusion of bcl-2 and p53 expression was observed in the undifferentiated and differentiated components (p53 but not bcl-2 expressed in the former).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207615 TI - Classification of CEA-related positivity in primary and metastatic malignant melanoma. AB - Using a panel of antibodies to carcinoembryonic antigen (CEA), in paraffin processed biopsy material patchy, predominantly membranous positivity was seen on tumour cells in 70 per cent of cases of superficial spreading melanoma, 60 per cent of nodular melanomas, and 75 per cent of secondary deposits studied with unabsorbed polyclonal anti-CEA only. No staining was seen using monoclonal anti CEAs. Localization of CEA to the cell membrane was confirmed with confocal microscopy. Immunoblotting of fresh frozen material detected CEA of around 180 kD in both primary and metastatic melanomas migrating with an apparent molecular weight of between 150 and 200 kD, indicating variable glycosylation of the protein. Recognition of an adhesive role for CEA with roles in immunolocalization and immunotherapy emphasizes the importance of more precise classification of CEA related positivity in human tumours. PMID- 8207616 TI - Immunohistochemical localization of syndecan-1 in normal and pathological human uterine cervix. AB - Expression of syndecan-1, a cell surface proteoglycan that binds growth factors and extracellular matrix components, was studied in normal and pathological human uterine cervix using immunohistochemical methods. Normal cervical squamous epithelium showed positive staining for syndecan-1 in all cell layers, except the basal cell layer, whereas endocervical columnar epithelium stained weakly. In non neoplastic reactive lesions, metaplastic squamous cells were positive for syndecan-1, whereas columnar cells showed weak or negative staining. In cervical condylomas, cells showing koilocytotic atypia were positive for syndecan-1. The progression of cervical intraepithelial neoplasia (CIN) grade I to grade III was associated with reduced syndecan-1 expression and localization of syndecan-1 to more superficial cell layers. In squamous cell carcinomas (SCCs), syndecan-1 expression correlated with histological differentiation, being absent from most poorly differentiated tumours. The results suggest that loss of syndecan-1 from atypical cells is an early event during cervical carcinogenesis and show a close association of syndecan-1 expression with preserved epithelial morphology and differentiation. PMID- 8207617 TI - The effect of inhibition of glutathione S-transferase P on the growth of the Jurkat human T cell line. AB - To investigate the possible role of glutathione S-transferase P (GSTP) in carcinogenesis and cell proliferation, ethacrynic acid (EA) was used to inhibit GSTP in the human Jurkat T cell line. At lower doses (0-30 microM), EA led to a decreased rate of proliferation as assessed by the MTT assay. This was associated with a decreased DNA S+G2/M phase population and also a dose-dependent increase in apoptosis. At concentrations of EA > 30 microM, cells suffered non-specific cytotoxic injury and underwent necrosis. The total cell number fell over the time course of the experiment. A resistant subculture of cells which proliferated in the presence of EA at 30 microM was selected by continuous growth in the presence of EA. Although this had a higher basal rate of apoptosis than control cells, it also showed a significantly larger growth fraction as assessed by flow cytometry. GSTP is frequently overexpressed in human tumours and animal models of carcinogenesis, and is regarded as a marker of the 'drug-resistant phenotype' of initiated cells. Our findings suggest that the role of GSTP in models of chemical carcinogenesis and in tumours may be its permissive effect on cell cycle activity and downregulation of apoptosis, thus allowing expansion of a population of initiated cells. PMID- 8207618 TI - Specific inhibition of acid proteinase secretion in Candida albicans by Lys-Nva FMDP. AB - Secretion of aspartic (acid) proteinase by Candida albicans is inhibited by the action of a new anticandidal agent, L-lysyl-L-norvalyl-[N3-(4-methoxyfumaroyl)]-L 2,3-diamino pro panoic acid (Lys-Nva-FMDP), at low, even sub-minimum inhibitory concentrations. The observed phenomenon is a direct consequence of inhibition of the enzyme, glucosamine-6-phosphate synthase. As a result of this inhibition, biosynthesis of candidal mannoproteins is markedly reduced. A possible correlation between general inhibition of mannoprotein biosynthesis and acid proteinase secretion is suggested. The reported inhibition of acid proteinase secretion by Lys-Nva-FMDP is more specific than the previously described effects of methyl patricin, 5-fluorocytosine and fenticonazole. PMID- 8207619 TI - Purification and characterization of fatty acid synthase from Candida albicans strain 4918 and two derived spontaneous cerulenin-resistant mutants. AB - Fatty acid synthase from three strains of Candida albicans (parental strain 4918, and two spontaneous cerulenin-resistant mutants, 4918-2 and 4918-10) has been purified and characterized. In all three cases the purification protocol included ammonium sulfate precipitation, fractionation with butyl-Toyopearl, differential centrifugation and sedimentation velocity centrifugation. Inclusion of protease inhibitors, aprotinin, leupeptin and pepstatin was a prerequisite to maximize recoveries. Polyacrylamide gel electrophoresis analysis demonstrated protocol efficacy and showed the apparent molecular mass of the two enzyme sub-units from each strain to be 195 kDa and 210 kDa. The Km (malonyl-CoA) and Vmax of each fatty acid synthase were similar. In contrast, inactivation kinetics of the respective enzymes in the presence of cerulenin showed enzyme activity from both mutants to differ significantly from the parent and from each other. Other experiments suggested in vivo cerulenin resistance of mutant strains is not solely attributable to enzyme alteration. PMID- 8207620 TI - Arrays of Candida albicans pseudohyphae that protect the organisms from neutrophil fungicidal mechanisms in experimental infections of mice. AB - Experimental subcutaneous Candida albicans infections in mice were used to examine the manner in which this pathogen is cleared in animals recovering from cyclophosphamide-induced leucopenia. In this system, infections at the inoculation sites progressed rapidly during a 6 day period of leucopenia to form arrays of parallel filamentous organisms that effectively isolated those in the interior from contact by neutrophils, even when the leucopenia had resolved. Dense collections of organisms also developed at sites of metastatic infection in the kidneys. A majority of the organisms were found to be viable when they were retrieved from the infected subcutaneous sites of animals that had recovered from leucopenia and whose abscesses had begun to drain spontaneously. Removal of the protective arrays of fungal cells appeared to be accomplished by drainage of abscess contents through the surface of the skin or into the collecting system of the kidney. Drainage of the subcutaneous abscesses did not occur in the cyclophosphamide-treated animals until after the neutrophilic infiltrates had developed, suggesting that this drainage process was mediated by neutrophils rather than by the organisms themselves. In summary, the above findings demonstrate that C. albicans infections in leucopenic hosts may progress to the extent that they would be very difficult to clear solely through the microbicidal processes of returning neutrophils. However, neutrophils also appear to promote the removal of masses of viable fungal cells to the exterior of the body. PMID- 8207621 TI - Application of neutral red staining for evaluation of the viability of dermatophytes and Candida in human skin scales. AB - The fungal elements observed by direct microscopic examination sometimes fail to grow on subsequent culture. To elucidate the cause of this discrepancy, the viability of dermatophytes and Candida in skin scales was evaluated by neutral red staining. Autoradiographic study using 3H-thymidine confirmed that grain positive cells (viable cells) were stained with neutral red, whereas negative cells (non-viable cells) were not stained. Taking this as a baseline, the correlation between neutral red-positive fungal elements in scales taken from 211 patients with tinea and 27 patients with cutaneous candidosis and cultures on Sabouraud glucose agar was studied. Strong positive correlations were found in both mycoses. These findings suggest that neutral red staining provides a useful method for evaluating the viability of dermatophytes and Candida in human skin scales. PMID- 8207622 TI - Immunochemical studies of heat-shock protein 80 of Histoplasma capsulatum. AB - A monoclonal antibody (MAb) of the IgG1 subclass, with greater activity to the yeast than the mycelial phase of Histoplasma capsulatum was raised and was found to predominantly recognize a molecule of 80 kDa by immunoblot. Enzymatic deglycosylation and chemical degradation, followed by reaction with MAb 69F on Western blots showed the molecule to be O-glycosylated, and immunofluorescence studies showed it to be heat-inducible and its distribution to be cytoplasmic and possibly cell membraneous. There was no apparent staining of the cell wall. Culture filtrate was positive by ELISA and Western blot when reacted with MAb 69F. In addition, ELISA and Western blot demonstrated that a similar epitope was present in other fungal species. The glycoprotein had a pI of approximately 4.7. N-terminal amino acid sequencing revealed this molecule to be homologous to members of the heat-shock protein 70 family and to a recently described antigen from H. capsulatum. PMID- 8207623 TI - Relationship between Candida albicans epidermolytic proteinase activity and virulence in mice. AB - Five strains of Candida albicans with previously characterized epidermolytic acid proteinase activity were evaluated for virulence following intravenous (i.v.) injection in mice. Increased proteinase activity was associated with increased virulence in female, NYLAR mice receiving 10(6) cells i.v. Mean mortality times (1.25, 2.0, 2.0, 4.25 and 19.6 days, in groups of 20 mice for each of the five strains) correlated directly with degree of proteinase activity. Three of the strains were selected for additional in vivo study and the association between increased proteinase activity and increased mortality rates was confirmed in dose response studies in two additional strains of mice. The mean survival times appeared to be independent of fungal growth rate in vitro. These results support the positive correlation between proteinase activity and virulence. PMID- 8207624 TI - Gelatinase activity of exoantigens from virulent and non-virulent isolates of Paracoccidioides brasiliensis. AB - Differences in the occurrence of components with gelatinase activity were detected among four isolates of Paracoccidioides brasiliensis: Pb339 and Pb18 (highly virulent), and Pb265 and Pb18AV (very low virulence). Culture filtrates from these isolates were electrophoresed in substrate gels and tested for gelatinase activity. Pb339 showed three enzyme bands of apparent molecular masses: 43, 53 and 78 kDa; Pb18 had two bands, one at 59 kDa and another with molecular mass higher than 78 kDa. Isolate Pb18AV showed only one band at 78 kDa and Pb265 exhibited a component of molecular mass which failed to enter the separating gel. PMID- 8207625 TI - Role of periodontal ligament receptors in the tactile function of teeth: a review. AB - The tactile function of the human periodontal mechanoreceptors has mostly been studied by psychophysical approaches. It was concluded that periodontal mechanoreceptors play a major role in the tactile function of teeth. It must be noted however that the interocclusal tactile threshold is not solely determined by periodontal mechanoreceptors but also by pulpal, muscular or articular receptors. While temporomandibular joint receptors play a minor role, muscular receptors are important in the discriminatory ability for a mouth opening of 5 mm and more. To discriminate between the contribution of periodontal and other receptors in the oral tactile function, future studies should use appropriate psychophysical methodologies and well-defined stimulus parameters. PMID- 8207626 TI - Effect of pre-experimental maintenance care duration on the development of gingivitis in a partial mouth experimental gingivitis model. AB - The present study was designed to evaluate if different periods of supervised oral hygiene prior to the experimental gingivitis trial have an effect on the amount of inflammation which develops in the 'toothshield' model. Two groups were compared. One group (Group A) was supervised over a 5-month period before experimental gingivitis. Six months later Group A participated in a second trial, this time receiving only a 1-month pretrial. A second group (Group B) which served as a control was supervised over a pre-trial period of 1-month prior to the start of the experimental gingivitis phase. During the pre-trial period all subjects undertook a regime of vigorous oral hygiene which included polishing of the test quadrant in the upper jaw and supervised subgingival brushing, interdental taping or the use of toothpicks. The presence of plaque and bleeding were assessed. Following the pre-trial period all plaque control measures in the experimental area were prevented during oral hygiene periods by the temporary placement of soft, loosely fitting vinyl toothshield guard. During this period they accumulated plaque rapidly and developed a generalized gingivitis. The results of this study indicate that, irrespective of the length of the pretrial period, subjects by group develop a comparable mean level of plaque and gingival bleeding. However, the extent to which gingivitis develops differs among individuals and was for a number of subjects not consistent. Therefore, in designing an experimental gingivitis trial care should be taken to include a sufficient number of subjects to account for individual variation. PMID- 8207627 TI - Studies of the angular reproducibility of positioning patients adjacent to an x ray tube: 1. Stent-rod based and extra-oral systems. AB - The usefulness of subtraction radiography for detecting small changes in crestal bone is dependent upon achieving reproducible geometry between x-ray beam and patient structures when serial radiographs are taken. This study evaluates 2 methods currently employed to maintain geometric correspondence: 1) a stent-based system which rigidly fixes a custom-made stent to the x-ray tube by the use of a rod and 2) an extra-oral system which positions a patient in the x-ray unit by means of ear rods. The projection of a light beam from a fixed subject reference was used to measure the change of the orientation of the reference at 2 different measurement times. The rod-stent system was able to maintain a discrepancy of less than 2 degrees 75% of the time over a time period of 6 months. For the extra oral system this ranged from 72% to 92% during a 1-month period. PMID- 8207628 TI - Increased respiratory burst activity is associated with normal expression of IgG Fc-receptors and complement receptors in peripheral neutrophils from patients with juvenile periodontitis. AB - The respiratory burst activity in peripheral neutrophils from nine patients with localized juvenile periodontitis (LJP) and age- and sex-matched healthy controls was studied by measuring the intensity of luminol-enhanced chemiluminescence (CL) induced by unopsonized and three differently opsonized zymosan particles, formyl methionyl-leucyl-phenylalanine (FMLP) or phorbol myristate acetate (PMA). The neutrophils from LJP patients showed in general more intense CL with all activators than did their controls. Particularly, the CL response induced by unopsonized zymosan particles and FMLP were significantly higher (p < 0.05 and 0.001). When comparisons were made between female LJP patients (n = 6) and matched controls, also serum-opsonized and IgG-opsonized zymosan particles produced CL was significantly increased (p < 0.05). In order to determine whether the elevated CL responses to zymosan particles were due to altered levels of the interacting receptors on neutrophil surface, an immunofluorescence analysis of the expression of IgG-Fc-receptors (FcR) and complement receptors (CR) was performed with flow cytometry. No significant difference in the expression of FcRII, FcRIII, CR1 and CR3 was detected in LJP group compared to controls. Since the elevated CL responses can not be explained by changes in receptor numbers it is hypothesized that the increased respiratory burst activity in LJP may be caused by altered post receptor signalling pathway. PMID- 8207629 TI - Regeneration of junctional epithelium and its innervation in adult rats: a study using immunocytochemistry for p75 nerve growth factor receptor and calcitonin gene-related peptide. AB - Junctional epithelium (JE) is a rapidly proliferating tissue that connects the gum to the tooth, that provides a free surface for bidirectional movement of substances between the body and the oral cavity, and that participates in defense against bacterial infection. It is innervated by numerous sensory nerve fibers that are immunoreactive (IR) for neuropeptides such as calcitonin gene-related peptide (CGRP), and for low affinity nerve growth factor receptor (p75-NGFR). Basal epithelial cells of the JE and of adjacent sulcular epithelium also have intense p75-NGFR-IR. In the present study we removed a wedge of the free gingiva and JE from the anterior side of the maxillary first molar of adult rats, and then studied the return of nerve fibers during tissue regeneration from 1-63 days after gingivectomy. The nerve fibers entered the adjacent healing sulcular epithelium before innervating the new JE, in both cases prior to return of epithelial cell p75-NGFR-IR. The regenerating nerve fibers completely bypassed the zone of epithelial down-growth (long junctional epithelium, LJE) that was briefly present along the tooth from 1-3 weeks after injury. The LJE did not have p75-NGFR-IR and was gradually replaced by a modified thicker regenerated junctional epithelium (RJE). The RJE was attached along the injured root surface, had numerous nerves in basal layers, and it had begun to regain p75-NGFR-IR staining of basal epithelial cells by 22 d. Regenerating nerve fibers at 6-10 d had unusually weak CGRP-IR and greatly increased p75-NGFR-IR. Both nerve stains had returned to normal by 3-6 weeks. The intense p75-NGFR-IR of regenerating nerves was found on both axonal and Schwann cell membranes using electron microscopic immunocytochemistry. In both the normal and regenerating JE, nerve fibers were rare in the attachment layers next to the anterior side of the maxillary first molar, compared to well-innervated basal layers. The complete avoidance of LJE by regenerating nerve fibers and its lack of p75-NGFR-IR suggest that its functions do not require innervation and that it does not make neurotrophic growth factors. PMID- 8207630 TI - [Histopathological findings of coronary artery lesions resected by directional coronary atherectomy]. AB - Eleven directional coronary atherectomy procedures were performed in seven patients with angina pectoris and four patients with myocardial infarction, 10 men and 1 woman aged 41 to 69 years (mean 57 +/- 7 years). The onset of angina pectoris or myocardial infarction had occurred 2 months to 17 years previously. The preoperative mean diameter of stenosis was 80 +/- 8%, and the mean residual diameter of stenosis was 6 +/- 9% (p < 0.01). Seven left anterior descending arteries and four right coronary arteries were treated. Five of the 11 patients received partial-thickness resections of medial tissue and two of the five patients received full-thickness resections of the media with adventitial tissue. No lesions showed aneurysms or perforations during coronary arteriography after the procedure. The resected tissue was examined microscopically. Intimal tissues stained with Masson's trichrome were classified into four groups according to the characteristics fibrous tissue and the amount of proliferative cells: Type I was old dense fibrous tissue, type II was relatively old fibrous tissue containing many proliferative cells, type III was new loose fibrous tissue containing many proliferative cells, and type IV was atheromatous plaque. The intimal tissues were type I in 48.0%; type II in 35.5%; type III in 14.8%; and type IV in 1.7%. Resected lesions without prior treatment (primary lesions) from five patients with histories of 3 months or less were characterized by much type II and type III tissue; (type I tissue, 33.8%; type II tissue, 51.1%; type III tissue, 14.5%; type IV tissue, 0.6%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207631 TI - [Effects of hot water bath or sauna on patients with congestive heart failure: acute hemodynamic improvement by thermal vasodilation]. AB - The acute hemodynamic effects of thermal vasodilation caused by exposure to hot water bath or sauna in chronic congestive heart failure were investigated in 32 patients (mean age 57 +/- 15 years old) with dilated cardiomyopathy (25 idiopathic and 7 ischemic). The clinical symptoms were New York Heart Association Class II in 2 patients, III in 17 and IV in 13, and the mean ejection fraction was 25 +/- 9% (9-44%). Exposure to hot water bath was for 10 minutes at 41 degrees C in a semi-sitting position, and to sauna for 15 minutes at 60 degrees C in a supine position using a special far infrared ray sauna chamber. Blood pressure, electrocardiogram, two-dimensional and Doppler echocardiograms, expiration gas, and intracardiac pressure tracings were recorded before (control), during, and 30 minutes after hot water bath or sauna. 1. The increase in oxygen consumption was only 0.3 Mets during hot water bath or sauna, and returned to the control level 30 minutes later. 2. The deep temperature in the main pulmonary artery increased by 1.0-1.2 degrees C on average at the end of hot water bath or sauna. 3. Heart rate increased significantly (p < 0.01) by 20 25/min during bathing and still increased 30 min later. 4. Systolic blood pressure did not change significantly during and after hot water bath or sauna, while, diastolic blood pressure decreased significantly during (p < 0.05) and after sauna (p < 0.01), and after hot water bath (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207632 TI - [Changes in gadolinium-DTPA enhanced magnetic resonance signal intensity ratio in hypertrophic cardiomyopathy]. AB - Serial gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA) enhanced magnetic resonance (MR) signal intensity ratios were measured in 6 normal subjects and 20 hypertrophic cardiomyopathy (HCM) patients to try to differentiate normal from disorganized myocardial tissue. Images were obtained at 10-minute intervals 5-60 minutes after Gd-DTPA (0.1 mmol/kg) injection. The signal intensity ratio (myocardial signal intensity/skeletal muscle signal intensity) was measured at both hypertropic and nonhypertrophic regions in each image at the apex and mid-ventricular levels. The signal intensity ratio was standardized to compare each case. Hypertrophic myocardium was classified into two types. Type I in 11 of 20 patients was visualized as a homogeneous image, while type II in the other 9 patients was revealed as a mixed isointensity and high intensity area. The peak value of the standardized signal intensity ratio at the apex level was 1.28 +/- 0.09 in HCM patients and 1.23 +/- 0.06 in normal subjects, and at the mid ventricular level was 1.26 +/- 0.07 in hypertrophic regions, 1.17 +/- 0.12 in non-hypertrophic regions, and 1.16 +/- 0.07 in normal subjects. Thirty minutes after Gd injection, the standardized signal intensity ratio at the apex level was 1.21 +/- 0.08 in HCM patients and 1.07 +/- 0.08 in normal subjects, and those at the mid ventricular level was 1.20 +/- 0.09 in hypertrophic regions, 1.11 +/- 0.11 in non-hypertrophic regions, and 1.04 +/- 0.06 in normal subjects. The delayed decay of the signal intensity ratio and high signal intensity ratio in Gd-DTPA enhanced MR images are useful in myocardial tissue characterization in hypertrophic cardiomyopathy. PMID- 8207633 TI - [Change in mitral valve area after percutaneous transvenous mitral commissurotomy: prediction of mitral valve restenosis]. AB - Factors indicating changes in mitral valve area after single-balloon percutaneous transvenous mitral commissurotomy (PTMC) were evaluated in 53 patients receiving PTMC by follow up for 3-48 months (mean 18 +/- 12 months) using serial transthoracic echocardiography to measure mitral valve area by planimetry. The echocardiographic scores of the mitral commissures and mitral valve, and other clinical variables were assessed. Mitral valve area showed an immediate increase from 1.1 +/- 0.3 to 1.8 +/- 0.3 cm2 (p < 0.01). There was a small but significant decrease in mitral valve area at follow-up to 1.6 +/- 0.4 cm2 (p < 0.01). Restenosis (a decrease in mitral valve area of more than 25% from immediately after PTMC to follow-up) occurred in nine patients (17%). There was no significant correlation between clinical or echocardiographic features and an increase in mitral valve area immediately after PTMC. The total echocardiographic score of the mitral commissures correlated with the decrease in mitral valve area at follow-up (r = 0.42, p = 0.002). Multiple regression analysis showed the total echocardiographic score of the mitral commissures was the best indicator of a decrease in mitral valve area at follow-up (p = 0.0059). Six of nine patients with restenosis had a commissure score of more than 3, while only five of 44 patients without restenosis had a commissure score of more than 3 (p < 0.01). Mitral valve area increases significantly immediately after PTMC, and decreases significantly at follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207634 TI - [Target heart rate for exercise echocardiography]. AB - The exercise stress test with a semi-supine position bicycle ergometer was evaluated in 10 normal subjects and five cardiac patients to define the appropriate target heart rate for exercise echocardiography. The normal healthy subjects were aged between 24 and 30 years, while the five patients with artificial aortic valves were aged between 13 and 54 years. The workload was continuously increased from 0 W to the maximum achieved workload at 20 W/min for normal subjects and 10 W/min for patients. Echocardiography was recorded every minute during the test procedure. End-diastolic and end-systolic dimensions were measured and ejection fraction was calculated. The ejection fraction at heart rates 50, 60, 70 and 80% of predicted maximum heart rate and at maximum workload were compared. Heart rates at the maximum workload for normal subjects were 76 to 94% (86.3 +/- 6.3%) of the maximum heart rate predicted from the age of the subjects and 70 to 102% (84.0 +/- 12.6%) for the patients. The largest election fraction values during exercise stress were obtained at 70% of the maximum predicted heart rate in normal subjects, and at 60% in the patients. The target heart rate for exercise echocardiography is 70% of the maximum calculated heart rate. PMID- 8207635 TI - [Long-term follow-up in patients receiving anticoagulation therapy: potency of therapy and complications]. AB - Many clinical trials have demonstrated the effectiveness of oral anticoagulation for the primary and secondary prevention of venous thromboembolism, myocardial infarction, systemic embolism and stroke. However, the relationship between potency and/or changes in anticoagulation therapy and frequency of complications is not clear. This study retrospectively investigated 157 patients (valvular heart disease 37, artificial valve replacement 19, atrial fibrillation 11, ischemic heart disease 55, post coronary artery bypass grafting 25, others 10: mean age 55 +/- 12 years) who received oral anticoagulation therapy for 4.9 +/- 3.2 years to investigate the development of complications. The thrombotest and prothrombin time were measured at follow-up examinations every month (mean interval 31 days). Target range of anticoagulation was 2.5 to 3.5 (international normalized ratio: INR). During the 770 patient-years of follow-up, seven major bleedings (cerebral, renal, gastrointestinal, etc.), 111 minor bleedings (subcutaneal, nasal, gum, etc. bleeding), 16 major thromboembolisms (cerebral, renal, etc. infarction) and 4 minor thromboembolisms (transient ischemic attack) were observed. INR at the onset of the complications was 2.93 +/- 0.41 in patients with bleeding and 1.81 +/- 0.46 in those with thromboembolism. INR was greater than 2.75 in all patients with major hemorrhage and less than 2.75 in those with major thromboembolism. Seventy-five percent of bleeding complications developed at the increasing phase of INR and 70% of thromboembolism at the decreasing phase. Cumulative rates free from bleeding complications with a mean INR of < or = 2.0, 2.0-2.5 and > 2.5 were 76.8, 62.8 and 45.5%, respectively, at 5 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207636 TI - [Evaluation of the lumen-plaque-wall alterations by intravascular ultrasound imaging after percutaneous transluminal laser angioplasty in peripheral arteries: comparison with angiographic findings]. AB - Intravascular ultrasound imaging was compared to angiography for evaluation of the changes in arterial lumen, atherosclerotic plaque and arterial walls after percutaneous transluminal laser angioplasty (PTLA) in peripheral arteries. Seventeen procedures using an argon laser angioplasty system (LASTAC system II) were performed in 13 patients with totally occluded lesions in the superficial femoral and iliac arteries. During or immediately after PTLA, a 30 MHz intravascular ultrasound catheter was inserted into the channel created by laser irradiation and adjunctive balloon dilatation. The outcome of PTLA was considered morphologically successful if the residual stenosis measured by intravascular ultrasound was 75% or less. Intravascular ultrasound showed eccentric plaques in 12 (71%), calcified plaques in 11 (65%), intraluminal thrombi in 2 (12%) and arterial wall injuries in 13 (76%) of the 17 lesions. PTLA was successful in 13 lesions and failed in 4. Occurrence of arterial dissections (38%) and mean residual stenoses (44 +/- 13%) were significantly (p < 0.05) lower in successful PTLA than in unsuccessful PTLA (100%, 89 +/- 3%). Eccentric stenoses, calcified plaques and arterial wall injuries were associated with poor success. Intravascular ultrasound detection of eccentric stenoses (71%), calcified plaques (65%) and arterial wall injuries (76%) was better than by angiography (29, 29, 47%). However, no significant correlation between intravascular ultrasound and angiographic findings could be found in quantitative estimation of the residual stenoses. Intraluminal thrombi were identified only by intravascular ultrasound. Angiography showed abnormalities in five (83%) of six lesions with medial injuries demonstrated by intravascular ultrasound, but none of the seven lesions with intimal injury. Intravascular ultrasound provides accurate diagnosis of eccentric stenosis, calcification, and arterial wall injury, and can quantitatively estimate residual stenosis and arterial wall injury during and immediately after PTLA in peripheral artery disease. PMID- 8207637 TI - [Diagnosis of sinus venosus atrial septal defect by transesophageal color Doppler and two-dimensional echocardiography]. AB - Diagnosis of sinus venosus atrial septal defect based on transthoracic color Doppler and two-dimensional echocardiography is often difficult. We recently experienced two cases of sinus venosus atrial septal defect which were correctly diagnosed using transesophageal color Doppler and two-dimensional echocardiography. Transthoracic color Doppler flow imaging did not demonstrate the atrial septal defect or the shunt flow across the defect in either case. Transesophageal two-dimensional echocardiography visualized a defect in the upper most portion of the interatrial septum in one case, and transesophageal color Doppler flow mapping detected a left-to-right shunt across the defect in both cases. Transesophageal color Doppler flow mapping also demonstrated the flow signal of the right upper pulmonary vein into the right atrium near its junction with the superior vena cava in each case. The diagnoses of sinus venosus atrial septal defect and combined partial anomalous pulmonary venous return were confirmed by surgery in both cases. Transesophageal color Doppler and two dimensional echocardiography are very useful in diagnosing sinus venosus atrial septal defect and combined partial anomalous pulmonary venous return. PMID- 8207638 TI - [Detection of right-to-left shunt flow in atrial septal defect using transesophageal color and pulsed Doppler echocardiography]. AB - The clinical significance of right-to-left (R-L) shunt flow dynamics in atrial septal defects (ASD) were investigated using transesophageal color and pulsed Doppler echocardiography in 30 patients with ASD of the ostium secundum type, including 20 with systolic pulmonary artery pressures (sPA) less than 40 mmHg, 4 with sPA of 40 to 60 mmHg, 3 with sPA of 90 mmHg or greater, 2 with pulmonic stenosis and 1 with Ebstein's anomaly. R-L shunting was detected by a shunt flow signal across the defect during a cardiac cycle. The timing of the R-L shunt was compared with various parameters obtained by echocardiography or cardiac catheterization. R-L shunt flow at the onset of ventricular contraction or closing phase of the tricuspid valve was detected in five patients with isolated ASD associated with increased mean right atrial pressure, but no severe pulmonary hypertension. R-L shunt flow during systole was detected in five of 26 patients with isolated ASD and tricuspid regurgitation and in one patient with Ebstein's anomaly. The tricuspid regurgitation signals in three of the five patients were directed toward the defect, while the other two had massive tricuspid regurgitation. R-L shunt flow during mid-diastole was detected in three patients without pulmonary hypertension. Massive left-to-right shunt flows occurred during the phase from end-systole to early diastole. R-L shunt flow during atrial systole was detected in three patients with severe pulmonary hypertension and two with pulmonic stenosis. The severe pulmonary hypertension patients, in particular, showed the aliasing signal as a high speed shunt flow, and in two of these, R-L shunt flow continued from atrial systole to early ventricular systole, and was also observed in early diastole. R-L shunt flow was detected in ASD patients with and without pulmonary hypertension, and was influenced by right atrial pressure at the phase of tricuspid valve closing, volume or direction of tricuspid regurgitation, rebound flow due to massive left-to-right shunt flow, grade of right ventricular distensibility or pulmonary hypertension, and other cardiac complications. PMID- 8207639 TI - [Low concentrations of epinephrine can augment shear stress-induced platelet aggregation]. AB - Platelet aggregation induced by shear stress is distinct from that induced by an agonist such as ADP or collagen. The physiological significance of shear-induced platelet aggregation was investigated by measuring the effects of the presence of physiological concentrations of epinephrine. Blood samples were taken from 10 normal volunteers who had received no drugs known to interfere with platelet functions for 1 month preceding the study. Blood was mixed with 1/10 volume of 3.1% sodium citrate solution. Platelet-rich plasma and platelet-poor plasma were prepared by centrifugation at 100 g for 15 min and 2,000 g for 15 min, respectively. The platelet count of platelet-rich plasma was adjusted to 3 x 10(5)/microliters. Shear-induced platelet aggregation in platelet-rich plasma was determined using a modified cone and plate viscometer controlled by a personal computer system. The intensity of light transmission was continuously recorded. The percent platelet aggregation was calculated according to the Lambert-Beer equation. Platelet aggregation occurred under both low (12 dyn/cm2) and high (108 dyn/cm2) shear stress. More significant aggregation was observed under high shear stress. The maximum percent platelet aggregation was 44.7 +/- 13.4%, which increased to 53.3 +/- 10.0% in the presence of 10 pg/ml epinephrine. With 100 pg/ml of epinephrine, shear-induced platelet aggregation induced by 12 dyn/cm2 shear significantly increased, but the effects on shear-induced platelet aggregation of 108 dyn/cm2 shear were not uniform. Shear-induced platelet aggregation is enhanced by physiological concentrations of epinephrine, which may be a cause of arterial thrombotic occlusion in sympathomimetic states. PMID- 8207640 TI - [A case of torsades de pointes probably caused by trimetaphan intoxication]. AB - A 42-year-old male was hospitalized in the surgical ward for abdominal pain due to stenosis of the splenic flexure of the colon and abscess around the stenosis. After segmental colectomy, the patient received intravenous continuous infusion of trimetaphan (Arfonad) to control his blood pressure. Twenty hours later, he developed bradycardia and hypotension followed by syncope. An electrocardiogram revealed marked prolongation of the QT interval and a prominent U wave associated with sinus bradycardia and/or sinus pause with junctional rhythm. Torsades de pointes type polymorphic ventricular tachycardia was the cause of the syncope, which appeared to be pause-dependent long QT syndrome caused by the ganglionic blocking action of trimetaphan in the presence of a hyperadrenergic state. PMID- 8207641 TI - Induction of neutralizing antibodies against human immunodeficiency virus type 1 using synthetic peptide constructs containing an immunodominant T-helper cell determinant from vpr. AB - Identification of immunodominant T-helper-cell determinants after natural infection is an important step in the design of immunogens for potential use in vaccination. Using cells from human immunodeficiency virus type 1 (HIV-1) infected individuals and a panel of peptides encompassing the sequence of the regulatory protein vpr from HIV-1, we identified the T-helper determinant QLLFIHFRIGCRHSR, which is active in 37.5% of these individuals. To gain insight on the efficacy of this peptide in helping induce neutralizing antibodies against a B-cell determinant (BD), we synthesized constructs containing B- and T-cell determinants and tested them in BALB/c mice, the highest responders to the T-cell determinant moiety among several strains tested. These immunogens induced antibodies against two chosen B-cell determinants from HIV-1IIIB gp160 (amino acids 310-322 from the V3 loop of gp120 and 736-751 from gp41) that were able to neutralize HIV-1 infection in vitro. The highest neutralization titer against HIV 1IIIB was obtained by immunization with the homopolymer of the construct containing the T-cell epitope from vpr and the B-cell epitope from the V3 loop. We believe that the immunodominant T-cell determinant from vpr is a promising epitope to consider in the design of future peptide vaccines. PMID- 8207642 TI - Effects of HIV infection on VH3 (D12 idiotope) B cells in vivo. AB - The abnormalities of B lymphocytes in human immunodeficiency virus (HIV) infection usually have been attributed to secondary consequences of disturbed immunoregulation. However, recent work has revealed avid binding of HIV gp120 to a conserved immunoglobulin motif unique to the VH3 gene family and the selective gp120-induced activation of VH3 B cells in vitro. This cross-sectional clinical study tests whether HIV infection is associated with a selective response of VH3 B cells in vivo. Levels of blood B cells and serum immunoglobulins (Ig) expressing the D12 idiotope of the VH3 gene family were measured in subjects of the Multicenter AIDS Cohort Study grouped according to clinical stages of HIV infection. A 3-fold elevation in D12 B cells was observed in HIV seropositive versus seronegative groups. This was selective for the D12 population, since total B cell numbers were identical in the two groups. The levels of D12 B cells and CD4 T cells were significantly correlated, and D12 B cells were markedly reduced in the AIDS group (4- and 10-fold, compared to the seronegative and seropositive groups). Analogous differences were also seen in the levels of serum anti-gp120 D12 Ig. This change in VH3 B cells among groups of HIV-infected individuals provides further evidence identifying gp120 as a VH3 B cell superantigen. PMID- 8207644 TI - Construction and characterization of a potent HIV-2 Tat transdominant mutant protein. AB - The human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) Tat proteins Tat 1 and Tat-2 stimulate transcription of the viral long terminal repeat (LTR) sequences and are required for efficient viral replication. A class of mutant Tat proteins, termed "transdominant mutants," has been described that possesses relatively low transactivation activity, yet is able to inhibit the function of wild-type Tat. These mutant proteins contain a nonfunctional TAR RNA-binding domain but apparently retain a functional activation domain. A potential limitation for therapeutic use of transdominant mutants described to date is their low but significant basal level of transactivation for the HIV-1 or HIV-2 LTRs. In order to make an improved transdominant mutant, we have constructed Tat 2 proteins that contain mutations in four contiguous arginines at residues 81 to 84 in the RNA-binding domain. Using purified proteins and in vitro RNA-binding assays, we verified that these mutant Tat-2 proteins are defective for TAR RNA binding. We also verified that these mutant Tat-2 proteins bind to a cellular protein kinase in vitro that we have previously shown to bind specifically to the Tat-1 and Tat-2 activation domain. Using plasmid cotransfection assays, we compared the phenotypes of these mutant Tat-2 proteins with the most potent Tat-1 transdominant mutant described to date. One Tat-2 mutant, named "R81-84A," was found to be equivalent to the Tat-1 mutant in ability to inhibit wild-type Tat transactivation of HIV-1 and HIV-2 LTRs. Moreover, the R81-84A mutant possessed a significantly lower basal level of transactivation than the Tat-1 mutant. The R81 84A Tat-2 mutant is therefore a promising reagent for future development as an anti-HIV agent. Additionally, our results suggest that wild-type Tat-2 transactivation of the HIV-2 LTR is especially sensitive to inhibition by transdominant mutants. PMID- 8207643 TI - Stimulation of HIV replication in mononuclear phagocytes by leukemia inhibitory factor. AB - This study examined the effects of leukemia inhibitory factor (LIF) on human immunodeficiency virus (HIV) replication in mononuclear phagocytes (MNP). LIF induced a dose-dependent increase in p24 antigen production in the chronically infected promonocytic cell line U1. The magnitude and time kinetics of the LIF effects were similar to interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF), other cytokines known to induce HIV replication in this cell line. To characterize mechanisms responsible for these LIF effects, levels of HIV mRNA, activation of the DNA binding protein nuclear factor (NF)-kB, signal transduction pathways, and potential interactions with other cytokines were analyzed. LIF increased steady-state levels of HIV mRNA at 2.0, 4.3, and 9.2 kB. This was detectable by 24 h and persisted until 72 h. The DNA binding protein NF-kB is a central mediator in cytokine activation of HIV transcription. NF-kB levels were higher in unstimulated U1 cells as compared to the parent cell line U937. In both cell lines LIF increased NF-kB activity. Induction of NF-kB and HIV replication by cytokines are at least in part dependent on reactive oxygen intermediates. The oxygen radical scavenger N-acetyl-L-cysteine, but not an inhibitor of nitric oxide synthase, inhibited LIF-induced HIV replication. LIF induces the production of other cytokines in monocytes but its effects on HIV replication were not inhibited by antibodies to IL-1, TNF, or IL-6. These results identify LIF as a stimulus of HIV replication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207645 TI - Predicting progression of HIV disease: usefulness of acid-dissociated p24 antigen. AB - To ascertain whether immune complex dissociation (ICD) improves the value of p24 antigen as a prognostic marker for progression of HIV infection, 53 patients were followed over a 3-year period, including at least one visit per year. All had CD4+ counts at entry > 400/mm3; progressors (n = 18) were defined as having CD4+ counts < 200/mm3 and nonprogressors (n = 35) as having CD4+ counts still > 400/mm3 at the end of follow-up. Serum specimens were collected at each annual visit and assayed for p24 antigen with and without ICD treatment. At entry, the percentage of progressors positive for ICD p24 antigen was significantly higher than the percentage of positive nonprogressors (39% versus 3%, p < 0.01). The sensitivity of p24 antigen over all visits in terms of predicting the progression increased from 61% before ICD to 83% after. The specificity of p24 antigen in terms of predicting progression decreased from 97% before ICD to 89% after. The relative risk of progression in individuals positive for p24 antigen was 6.7 before ICD and increased after ICD to 12.7. When evaluating the respective prognostic value of the p24 antigen and of the ICD p24 antigen, only ICD p24 was significant (RR 10.2, 95% CI 2.2-46.9). ICD p24 antigen appears to be a marker of progression that may be detected earlier than p24 antigen without ICD. PMID- 8207646 TI - The HIV wasting syndrome: a review. AB - The HIV wasting syndrome and other HIV-associated weight loss is a major problem in HIV-infected patients. The available data strongly suggest that wasting is associated with decreased survival. It may also further impair immune function. A variety of etiologies probably contribute to this wasting, including hypermetabolism, alterations in metabolism, lessened oral intake, malabsorption, cytokine effects, and endocrine dysfunction. The relative contributions of each of these etiologies to wasting probably varies considerably from patient to patient. Successful treatment calls for identification of possible etiologies of wasting in the individual patient with AIDS. Further treatment may include treating underlying conditions and controlling such symptoms as diarrhea, nausea, or fever. Nutritional support, including both parenteral and enteral nutrition, has shown some promise of efficacy, and a variety of drugs appears to be helpful. Future treatment to reverse wasting may include the use of several of these agents in combination. Currently, there is much that clinicians can do to evaluate and treat the HIV wasting syndrome, with significant potential benefits to their patients. PMID- 8207647 TI - Bleach use and HIV seroconversion among New York City injection drug users. AB - We employed a nested case-control study design to evaluate the efficacy of bleach cleaning of needles and syringes among injecting drug users (IDUs) as a means of preventing human immunodeficiency virus (HIV) infection. Sixteen HIV seroconverters who responded to bleach use questions and who reported injecting with shared or used equipment in the 6 months prior to their first positive visit were compared with 89 controls. Controls had remained HIV-seronegative at two or more visits, reported injecting with shared or used equipment, responded to bleach-cleaning questions, and were seen at recall visits +/- 6 months from the date of seroconversion of the index case. Risk factors associated with HIV seroconversion in univariate analyses were a history of sexual intercourse with an HIV-infected partner and the frequency of speedball (mixed heroin and cocaine) injections. After adjusting for confounders, we found no evidence that bleach use protected against HIV infection. PMID- 8207648 TI - Heterosexual transmission of human immunodeficiency virus type 1 from transfusion recipients to their sex partners. AB - Using lookback procedures and other methods, we identified and then prospectively followed human immunodeficiency virus type 1 (HIV-1)-infected transfusion recipients and their sex partners to determine AIDS incidence and risks of heterosexual transmission of HIV-1. At enrollment, 7 of 32 (21.9%) female partners of male recipients were themselves infected with HIV-1, as compared with none of 14 male partners of female recipients (p = 0.08). No additional episodes of transmission were observed. The prevalence of advanced immunodeficiency at enrollment was similar in male and female recipients. Male recipients with advanced immunodeficiency (CD4+ lymphocyte count < or = 0.20 x 10(9)/L or a history of clinical AIDS) at enrollment were more likely to have infected their female partners (odds ratio = 7.9; p = 0.03) than men with neither condition. Similarly, AIDS-free survival, as estimated by the product-limit method, was lower among male transmitters than among male nontransmitters (p = 0.01). Transmission was not associated with frequency of unprotected vaginal intercourse. Our data suggest that HIV-1-infected men who develop immunodeficiency rapidly are more likely to infect their sex partners and that the greater efficiency of male-to-female HIV-1 transmission is not explained by a greater number of sexual contacts or more advanced immunodeficiency in index subjects. PMID- 8207649 TI - Risk factors for HIV-1 and HIV-2 infection in pregnant women in Dakar, Senegal. AB - This study examines the prevalence and risk factors for Human Immunodeficiency Virus type 1 (HIV-1) and type 2 (HIV-2) infection in pregnant women in Dakar, Senegal. From April 1991 to January 1993, 9,518 pregnant women were interviewed and serologically tested for antibodies to HIV-1 and HIV-2; 26 (0.3%) were HIV-1 seropositive, 44 (0.5%) were HIV-2 seropositive, two (0.02%) were dually seropositive, and 9,448 (99.3%) were seronegative. Guinea-Bissau nationality and age > 25 years were associated with HIV-2 infection, whereas parity < or = 2 was associated with HIV-1 infection. Among women who gave birth to live infants, shorter length of union with the partner and having been married more than once were associated with HIV-2 infection, whereas age < or = 25 years was associated with HIV-1 infection. Information gained by this study may help target intervention strategies for preventing maternal HIV infection and understanding biological differences between the two viruses. PMID- 8207650 TI - Mycobacterium tuberculosis and its purified protein derivative activate expression of the human immunodeficiency virus. AB - To examine the effects of Mycobacterium tuberculosis on human immunodeficiency virus type 1 (HIV-1) expression, the monocytoid cell line U1 containing integrated provirus was incubated with the H37Ra strain of M. tuberculosis. This resulted in heightened expression of virus in supernatant that was partially inhibited by antibody to tumor necrosis factor-alpha (TNF-alpha). Purified protein derivative (PPD) prepared from M. tuberculosis also could activate HIV expression, and this was less affected by anti-TNF antibody. PPD could activate the HIV promoter in both U937, the monocytoid cell line from which U1 was derived, and Jurkat, a CD4+ lymphoid line. Activation was abolished by mutations in the nuclear factor (NF)-kB binding domains. Jurkat cells transfected with a plasmid construct linking 8 NF-kB binding domains to the chloramphenicol acetyltransferase (CAT) gene showed increased activity of the reporter gene after activation with PPD. Transcriptional activation of HIV expression by mycobacteria and mycobacterial products may enhance propagation of HIV in monocytoid and lymphoid cells. This may result in accelerated HIV disease progression in persons coinfected with M. tuberculosis. PMID- 8207651 TI - Polymorphism at the tumor necrosis factor-alpha locus and susceptibility to toxoplasmic encephalitis, ultraviolet B-induced immune impairment, and mouse AIDS. PMID- 8207652 TI - Hiccups in people with AIDS. PMID- 8207653 TI - HTLV-II infection is rare in patients with large granular lymphocyte leukemia. PMID- 8207654 TI - Interpreting the power law relationship observed in studies of sexual behaviour. PMID- 8207655 TI - HIV prevalence and incidence among injection drug users in Los Angeles. PMID- 8207656 TI - HIV, drug-use paraphernalia, and bleach. PMID- 8207657 TI - Historical perspective on the use of bleach in HIV/AIDS prevention. AB - In 1986, community outreach workers began distributing small bleach bottles to injection drug users (IDUs) in San Francisco as a simple means for them to reduce their risk of infection with HIV and other pathogens by quickly flushing their syringes with bleach. At inception, the intervention was based on four assumptions: (a) sole reliance on expanded drug treatment capacity could not achieve HIV prevention goals, (b) legal barriers made syringe distribution or exchange schemes unfeasible, (c) IDUs would act in their own interest if the measures offered were acceptable to them, and (d) using bleach would diminish the risk of HIV transmission from reusing injection equipment. Following successful implementation of this program in San Francisco, similar programs were developed in many locations. These programs serve as the principal means of preventing needle-borne HIV infection among IDUs not enrolled in drug abuse treatment in the United States. Needed are definitive laboratory studies to determine the effectiveness of bleach decontamination as presently used by IDUs. PMID- 8207658 TI - In vitro activity of readily available household materials against HIV-1: is bleach enough? AB - This report describes experiments assessing the effectiveness against HIV of potential disinfecting agents that are commonly available to IDU when they are sharing syringes. We exposed cell-free HIV, HIV-infected cells, and HIV-infected blood containing known quantities of HIV to household cleaning agents, alcohols, peroxide, and highly acidic materials for 1 min, in order to examine the effects of these materials on the infectivity of the HIV. Undiluted liquid laundry bleach and dilute liquid dish detergent reduced the number of culturable HIV to an undetectable level under the experimental conditions used. Diluted bleach was not completely effective. Other potential disinfecting agents, including ethanol, isopropyl alcohol, and hydrogen peroxide, were unable to disinfect high numbers of HIV-infected cells or infected blood. Liquid dish detergent warrants further study as a possible acceptable alternative to bleach. Our data provide support for recommendations to IDU that they disinfect shared syringes every time between users with full-strength liquid laundry bleach to reduce their risk of acquiring or transmitting HIV. When bleach is not available, liquid dish detergent or other available disinfecting agents such as rubbing alcohol, hydrogen peroxide, or high alcohol content beverages are more effective than water at disinfecting HIV, recognizing that these materials are less effective than bleach. Although these materials are effective, they should not be viewed as a substitute for decreased sharing of injection equipment by IDU, or increased availability of sterile needles and syringes. PMID- 8207659 TI - Preliminary laboratory studies of inactivation of HIV-1 in needles and syringes containing infected blood using undiluted household bleach. AB - To evaluate the effectiveness of bleach disinfection of injection equipment, we tested HIV-1 inactivation by household bleach in needles and syringes. We obtained blood from HIV-1 infected injecting drug users (IDUs), placed small aliquots in needles and syringes. Blood with and without anticoagulant was incubated at room temperature for 3, 6, 18, and 24 h, and some needles and syringes from each condition were exposed to undiluted bleach for 15 and 30 s. The needles and syringes were then rinsed and the rinses were used to inoculate peripheral blood mononuclear cells (PBMNCs). HIV-1 replication was monitored using p24 enzyme linked immunosorbent assay (ELISA). We describe results that HIV 1 is inactivated in clotted and unclotted blood allowed to stand at room temperature for 3, 6, 18, and 24 h in needles and syringes using undiluted household bleach at 30 s of exposure time. These results are consistent with earlier findings that micropellets of HIV-1 were inactivated by bleach under similar conditions of exposure to bleach; 10% bleach was not effective at an exposure time of 30 s and undiluted bleach was not effective at an exposure time of 15 s to inactivate HIV-1 in clotted blood. Bleach concentration and exposure time are critical and HIV disinfection may not occur with inadequate exposure to bleach HIV. PMID- 8207660 TI - Field effectiveness of needle disinfection among injecting drug users. AB - To examine the putative protective effect of disinfectant use on HIV seroconversion among injecting drug users, we conducted a nested case-control study of black heterosexuals comparing 34 HIV seroconverters with 154 persistent seronegatives matched on gender, cocaine injection (yes/no), date of study entry, and duration of follow-up. Injecting drug users who reported using disinfectant all the time had an odds ratio of seroconversion of 0.87, as compared with those who reported no use of disinfectants; the corresponding odds ratio was 1.00 for those who used disinfectants less than all the time. We examined the effect of drug use and sex practice variables, and responses to a socially desirable responding scale as possible confounders for the effect of needle disinfection on HIV seroconversion; the adjusted odds ratios for disinfectant use and HIV seroconversion were unchanged in this analysis. Despite limited statistical power and the potential for residual confounding, these data suggest that disinfection of injection equipment is not a substitute for abstinence from drugs or use of sterile injection equipment. PMID- 8207661 TI - Inadequate bleach contact times during syringe cleaning among injection drug users. AB - Objectives were to measure syringe cleaning strategies used by injection drug users (IDUs) and to assess syringe contact with bleach during cleaning demonstrations. IDUs were interviewed about cleaning activities during their most recent injection episode; they demonstrated these activities on videotape. Coders reviewed the videotapes, categorized activities, and used stop watches to record bleach exposure. Of 161, 146 subjects reported cleaning at last injection, 85 (58%) of 146 used full strength bleach. Of bleach users, 20% had total contact time (duration of bleach inside syringe) of > or = 30 s; combining draw (time taken to fill syringe) and contact times, 54% of bleach users had total "flush" times of > or = 30 s. Median observed time per bleach flush was 16 s. Median reported cleaning times were twice as long as observed. Recent reports indicate 30 s of exposure to undiluted bleach is necessary to inactivate HIV in the laboratory; here, 80% of IDUs using bleach had contact of < 30 s. Judgment of contact time was inaccurate. On average, instructions advocating two bleach flushes may reach 30 s; here, half the subjects had insufficient time with two flushes. The majority showed inadequate techniques, therefore, alternate cleaning strategies should be developed. PMID- 8207662 TI - Compliance to bleach disinfection protocols among injecting drug users in Miami. AB - Bleach cleansing of injection equipment has been recommended to reduce the risk of human immunodeficiency virus (HIV) transmission associated with the reuse of injection equipment by injecting drug users (IDUs). We evaluated the recall and performance of the most commonly recommended bleach cleansing procedure of two complete fillings of the syringe with bleach, followed by two complete fillings with rinse water, and not putting used bleach and water back into source containers. IDUs were taught this procedure on enrollment in an HIV prevention demonstration project in Dade County, Florida. During follow-up session 6-12 months after initial training, the knowledge and ability of IDUs to perform bleach cleansing were assessed by trained observers using a standardized method. In 1988-90, we assessed the knowledge and ability of 450 IDUs to perform the bleach cleansing procedure taught at enrollment. More than 90% of IDUs assessed performed the basic steps. However, only 43.1% completely filled the syringe with bleach and only 35.8% completely filled the syringe with bleach at least twice. Substantial proportions of IDUs did not perform all the steps of the previously taught bleach cleansing procedure. Compliance decreased as the number of steps required was increased. This limited compliance may make bleach cleansing less effective and suggests that some IDUs may fail to adequately disinfect injection equipment and therefore sterile needles and syringes are safer than bleach cleansed ones. Compliance testing can help assess the effectiveness of HIV prevention programs. PMID- 8207663 TI - Extraction and analysis of indole derivatives from fungal biomass. AB - The occurrence and extraction of indole derivatives in six species from four genera of higher fungi were investigated. By using pure methanol for extraction of the mushrooms analysis revealed the highest concentrations of psilocybin and baeocystin. The psilocin content of the species was higher by using aqueous solutions of alcohols than with methanol alone but was an artificial phenomenon caused by enzymatic destruction of psilocybin. The extraction with dilute acetic acid yielded better results than with the water containing alcohols. The simple one-step procedure with methanol for the quantitative extraction is still the safest method to obtain the genuine alkaloids from fungal biomass. PMID- 8207664 TI - Effect of immune serum, an antibiotic, and a corticosteroid used alone or in combination on experimental leptospirosis in Mongolian gerbils (Meriones unguiculatus). AB - We studied the effects of immune sera, an antibiotic, and a corticosteroid used alone or in combination on leptospira infection in Mongolian gerbils (Meriones unguiculatus). The results suggest that the combined used of immune serum and corticosteroid (pledonizoron: PZ) inhibits the effects of serum and the marked effects of antibiotic (procaine penicillin-G: PC-G) on leptospirosis. PZ had no effects and rather shortened the survival period. PZ did not affect the effects of PC-G when used in combination. These results suggest that treatment of leptospirosis with corticosteroids requires special caution. PMID- 8207665 TI - Petite mutants of sophorolipid-producing Candida yeasts. AB - Treatment of both Candida apicola IMET 43747 and Candida bombicola ATCC 22214 with N-methyl-N'-nitro-N-nitroso guanidine resulted in formation of auxotrophic mutants and cytochrome oxidase negative mutants. The deficiency of intact cytochrome oxidase did not affect the ability to produce sophorose lipid. This indicates that intact mitochondrial energy supplying system is not necessary for the production of the extracellular sophorose lipids by both Candida yeasts. PMID- 8207666 TI - Iron supply of Pasteurella multocida and Pasteurella haemolytica. AB - Pasteurella multocida and Pasteurella haemolytica do not produce hydroxamate- or phenolate type siderophores. However, transport- and utilization systems could be detected for the well known siderophores ferrioxamine B, E, G, rhizoferrin and the intermediate 2,3-dihydroxybenzoic acid by means of cross-feeding tests in both Pasteurella species. Enterobactin and ferrichrome did not feed any of the Pasteurella strains tested. Additionally, alpha-ketoacids and alpha-hydroxyacids such as pyruvic acid, alpha-hydroxyisovaleric acid and others acting as primary metabolites enabled growth of P. multocida and P. haemolytica under iron limitation. PMID- 8207667 TI - Analgesic and antiinflammatory effects of some new 6-acyl-3-substituted-2(3H) benzoxazolone derivatives. AB - 6-Acyl-2(3H)-benzoxazolone derivatives were reacted with 4-substituted phenacyl bromide in ethanol to give the corresponding 6-acyl-3-[(4 substitutedbenzoyl)methyl]-2(3H)-benzoxazolones . The compounds were screened for their analgesic, antiinflammatory activities. The eight compounds synthesized showed high analgesic activities and further investigation revealed compounds 3, 6 and 7 to be potent inhibitors of carrageenan- and arachidonic acid-induced paw edema. The PGE2 isolated from the carrageenan paw edema fluid was also significantly low in mice treated with compounds 3, 6 and 7. PMID- 8207668 TI - A novel technique for the one-step preparation of liposomes and nonionic surfactant vesicles without the use of organic solvents. Liposome formation in a continuous gas stream: the 'bubble' method. AB - A novel technique for the preparation of liposomes without the use of organic solvents, detergents, or high shear forces is described. Introduction of inert gas bubbles into a coarse dispersion of nonhydrated (phospho)lipids (hydrogenated soybean phosphatidylcholine and/or dicetylphosphate as charge-inducing agent) or nonionic surfactant (C18EO3)/cholesterol mixtures produces stable liposome/niosome dispersions with a mean particle size in the range between 0.2 and 0.5 microns. The influence of addition of cholesterol and the effect of the ionic strength of the aqueous medium on the preparation process of liposomes was investigated. An hypothesis for the mechanism of liposome formation under the chosen conditions is presented and discussed. PMID- 8207669 TI - Separation of drugs by packed column supercritical fluid chromatography. 2. Antidepressants. AB - Antidepressants can be rapidly and efficiently separated by packed-column supercritical fluid chromatography with a tertiary mobile phase. Ten antidepressants were nearly baseline resolved in < 6 min without programming. Calculated detection limits with a 5-microL injection volume were as low as 88 ppb. The effects of temperature, pressure, and modifier concentration on retention and selectivity were studied. Changing modifier concentration caused significant changes in selectivity. Several relationships between solute structure and selectivity changes were noted. PMID- 8207670 TI - Metal complexes of anhydrotetracycline. 1. A spectrometric study of the Cu(II) and Ni(II) complexes. AB - Anhydrotetracycline (AHTC), one of the major toxic decomposition products of the antibiotic tetracycline, contains several potential binding sites to metal ions. The acidity constants of the ligand were calculated in aqueous medium (I = 0.1 M) at 25 and 37 degrees C. We found pKa1 = 3.23 +/- 0.08, pKa2 = 5.94 +/- 0.09, and pKa3 = 8.48 +/- 0.02 at 25 degrees C and pKa1 = 3.12 +/- 0.09, pKa2 = 5.86 +/- 0.03, and pKa3 = 8.38 +/- 0.04 at 37 degrees C. The coordination of AHTC to Cu(II) and Ni(II) ions was studied in the solid state as well as in buffered aqueous solution at pH 10.0. At this pH, the formation of the two CuL2 and CuL species was indicated (log beta 1 = 8.41 +/- 0.04 and log beta 2 = 12.55 +/- 0.05), but only the formation of the NiL complex (log beta = 5.74 +/- 0.04) was identified. Spectroscopic data confirm the previous assignment of the C11 and C12 oxygens as the coordination sites, yielding six-membered ring chelates and excluding complexation through any of the potential binding positions on ring A. PMID- 8207671 TI - Cetyl myristoleate isolated from Swiss albino mice: an apparent protective agent against adjuvant arthritis in rats. AB - Cetyl myristoleate was isolated from National Institutes of Health, general purpose, Swiss albino mice that were immune to the polyarthritis induced in rats with Freund's adjuvant. This substance, or material synthesized from cetyl alcohol and myristoleic acid, afforded good protection against adjuvant-induced arthritic states in rats. In limited comparisons, cetyl oleate, also found in Swiss albino mice, gave lesser protection, whereas cetyl myristate and cetyl elaidate, the trans-isomer of cetyl oleate, appeared to be virtually ineffective. Dosage of the protective compound as well as the site of injection of Freund's adjuvant was important. PMID- 8207672 TI - Solid-state properties and crystal structure of gliclazide. AB - The solid-state characterization of gliclazide, for which no analytical standard was previously available, has been completed by extensive structural and physical analytical examination. The crystal and molecular structure for gliclazide was determined by single-crystal X-ray diffraction. Gliclazide crystallizes in the monoclinic space group P2(1)/n, with the unit cell dimensions a = 10.828(2) A, b = 14.342(19) A, c = 11.005(6) A, and with beta = 106.97(2) degrees, V = 1635(12) A3, and Z = 4. The gliclazide molecule is articulated in an open extended conformation about the sulphonylurea nucleus. Two gliclazide molecules form a complex with one calcium atom to facilitate the transport of calcium ions across the pancreatic beta cells necessary for the stimulation of insulin secretion. The only conformation that allows for the close apposition of the tolyl groups, and therefore the formation of the gliclazide:calcium complex, is the extended conformer. PMID- 8207673 TI - Aromatic and amine substituent effects on the apparent lipophilicities of N-[(2 pyrrolidinyl)methyl]-substituted benzamides. AB - Lipophilic properties of 92 dopamine D-2 receptor antagonists belonging to the substituted benzamide class of compounds (orthopramides and methoxysalicylamides) were determined by octadecylsilane reversed-phase HPLC. The apparent lipophilicity at pH 7.5 (log kw) was obtained from the chromatographic capacity factors in 0.02 M3-(morpholino)propanesulfonic acid (MOPS) buffer at various concentrations of methanol. The experimental log kw values were validated by comparison with the apparent octanol-water partitioning (log Papp) of 15 compounds of low to medium lipophilicity. The global lipophilicity of the neutral molecule (log kwo) was obtained by correcting for ionization of the amine and the phenol, using known relationships for the effects on the pKa (where Ka is the dissociation constant) of aromatic and aliphatic substituents. Multiple regression analysis showed that log kwo can be expressed as the sum of pi contributions and a cross correlation term (sigma rho sigma) for interactions between the aromatic substituents. Comparison between the methoxysalicylamide (raclopride) series and the orthopramide (sulpiride) series demonstrated that an aromatic 6-hydroxy group increased log kw by 0.4 in the 5-halogen series and by 0.8 in the 5-alkyl series, and that a 6-methoxy group decreased log kw by 0.5. These paradoxical effects can be explained by the masking of the polarity of the amide caused by the 6-hydroxy group forming an intramolecular hydrogen bond with the amide carbonyl group. Introduction of an additional ortho-methoxy substituent had the opposite effect because the resulting steric hindrance prevents the amide moiety from adopting a coplanar conformation with the benzene ring. The presence of a substituent in the aromatic 3-position lowered log kw by 0.3 via a combination of steric and electronic influences on the adjacent 2-methoxy group, causing a weakening of the hydrogen bond between the amide and the oxygen atom of the 2-methoxy group. As a result, halogen and alkyl substituents in the 3 position increase the apparent lipophilicity only half that of similar substituents in the 5-position. Substitution with omega-fluoroalkoxyl groups in the aromatic 2- and 3-positions and with omega-fluoroalkyl groups in the 5 position reduced lipophilicities by 0.5 as compared with the corresponding desfluoro derivatives, thereby making them equivalent to an alkyl derivative with one less carbon atom in the chain. In contrast, substitution on the pyrrolidine nitrogen atom with a 2-fluoroethyl or a 3-fluoropropyl group produced compounds with apparent lipophilicities approximately 1.5 and approximately 0.5 higher, respectively, than those of the corresponding N-ethyl derivatives.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8207674 TI - Interaction of anionic compounds with gelatin. II: Effect on some physicochemical properties of gelatin. AB - The interaction of gelatin with four monosulfonated or monocarboxylated azo dyes was investigated by measuring the surface tension and intrinsic viscosity of gelatin solutions containing the dyes at different concentrations, the rigidity and melting point of their gels, and the moisture regain of their films. The dyes, which were used as models for anionic drugs, differed in the size of their aromatic hydrocarbon moieties. Surface tension measurements showed that the gelatin did not affect the critical micelle concentration of the free dyes and that the bound dyes increased the surface activity of the gelatin. The dyes reduced the intrinsic viscosity of gelatin by as much as 2/3. They also lowered the rigidity and the melting point of dilute gelatin gels and reduced the moisture regain of dry gelatin films. These changes became more pronounced with increasing dye concentrations. The effectiveness of the dyes in producing these changes increased with the size of their hydrocarbon moieties because, as had been shown in a previous study, increasingly larger hydrocarbon moieties increased the binding of the dyes to gelatin. At the pH of the measurements, which was 1.9 units below the isoelectric point of the gelatin, the gelatin was a cationic polyelectrolyte. Binding of the dye anions by ion pairing, hydrogen bonds, and other secondary valence forces rendered the gelatin less ionic and less hydrophilic, which accounts for the present observations. PMID- 8207675 TI - Alkaline hydrolysis of cefotaxime. A HPLC and 1H NMR study. AB - A kinetic study on the alkaline hydrolysis of cefotaxime at pH 10.5 and 37 degrees C has been carried out by using HPLC and 1H NMR. The main resulting degradation products have been isolated and identified. These include, apart from the well-known deacetylcefotaxime, the exocyclic methylene derivative, the 7 epimer of cefotaxime and the 7-epimer of deacetylcefotaxime. The kinetic constants involved in the process have been determined and according to the experimental results the attack of the hydroxyl group on the ester function bonded to the 3'-carbon is the fastest step in the proposed kinetic scheme. It should be emphasized that the base-catalyzed epimerization of the hydrogen at the 7 position clearly depends on the presence of a good electron-withdrawing group at C(3'). On the other hand, no hydrolysis of the amide at position 7 was detected. PMID- 8207676 TI - Synthesis and some physiochemical properties of 2-hydroxy-N-(3,4-dimethyl-5 isoxazolyl)-1,4-naphthoquinone 4-imine derivatives. AB - Some derivatives of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)- 1,4-naphthoquinone 4 imine (3), a poorly soluble drug, were synthesized in an attempt to improve their physicochemical properties. The new compounds were characterized by spectroscopic methods including an iterative NMR method (the LAOCOON III program). The physicochemical properties such as solubility, relative lipophilicity (RM), and partition coefficients (Leo-Hansch fragmental system) were determined. Some derivatives were more lipophilic than 3 and one was water soluble. In vitro antibacterial activity was also reported for some derivatives. PMID- 8207677 TI - Isoxazoles. 8. Preformulation studies of an isoxazolylnaphthoquinone derivative. AB - The degradation kinetics of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4 naphthoquinone 4-imine (1) in a 25% solution of ethyl alcohol in water has been studied. The rate constants were observed to follow pseudo-first-order kinetics in all cases. The pH-rate profile indicated a negligible decomposition at pH values higher than its pKa2 value [5.4 +/- 0.14 (*n = 6)]. Un-ionized 1 was subject to specific acid catalysis. The ionic strength did not affect the stability of the drug. These data can be used to develop a stable oral liquid dosage form of the drug. PMID- 8207678 TI - Prodrugs of 2',3'-didehydro-3'-deoxythymidine (D4T): synthesis, antiviral activity, and rapid pharmacokinetic evaluation. AB - A series of 5'-derivatives and modified pyrimidine analogues of 2',3'-didehydro 3'-deoxythymidine (d4T, stavudine, 1) were synthesized to determine their potential as oral prodrugs of d4T. Utilizing a screen developed for the rapid evaluation of a variety of prodrugs in mice, it was determined that 5'-acetate 2 provided comparable plasma levels of d4T after oral administration of the prodrug to that when d4T was administered alone. The relative oral bioavailability of methoxy acetate 3 and cyclohexyl carbonate 5 was 79 and 41%, respectively. Dihydropyridine ester 6 did not provide detectable levels of d4T up to 1 h after oral administration of 6. Thiopyrimidines 8 and 9, as well as aminopyrimidine 10 also failed to provide measurable levels of d4T after oral administration. 5' Derivatives 3, 5, and 6 showed similar activity to that of d4T against HIV and MuLV, as did 5'-benzoyl-4-thio derivative 8. However, the corresponding 4-thio 5' alcohol 9 was inactive. PMID- 8207679 TI - Role of conductivity in iontophoresis. 2. Anodal iontophoretic transport of phenylethylamine and sodium across excised human skin. AB - The anodal iontophoretic transdermal delivery of a model cation, phenylethylamine (PEA), across excised human skin was investigated to define the role of conductivity in iontophoresis. The ratio of the specific conductance of PEA in deionized-distilled water to that of the solution applied in the donor compartment (buffer+PEA) was employed to assess the relationship between the flux of PEA and the conductivity. The flux of PEA was linearly related to the ratio of specific conductance at 5 and 20 mM PEA for a variety of experimental conditions. A curvilinear relationship was observed at 1 mM PEA concentration, particularly when the conductivity of the donor solution was low. It is therefore hypothesized that a threshold conductivity in solution exists above which a linear relationship between iontophoretic flux and specific conductance is observed. The present study confirms that conductivity of an ion in a solution provides a simple means of estimating the competitive transport between solute and other ions during transdermal iontophoresis. PMID- 8207680 TI - Application of a variable direction hysteresis minimization approach in describing the central nervous system pharmacodynamic effects of alfentanil in rabbits. AB - The relationship between the concentration of a drug and its pharmacologic effect is of central interest in pharmacodynamics. Various compartmental and noncompartmental methods have been proposed for elucidating this relationship when the plasma drug concentration and effects are both measured. Although the relationship between drug input and the pharmacologic effect is equally useful, it has not received as much attention. A system analysis hysteresis minimization pharmacodynamic method was developed to describe the central nervous system effects of alfentanil in rabbits. The spectral edge frequency (SEF) was used as the effect measure and the infusion rate as the pharmacokinetic variable. The sigmoid Emax and cubic polynomial representations of the transduction relationship were investigated in modeling the collapsed hysteresis loop. The results indicated that alfentanil has a relatively rapid biophase equilibration time (t50 = 6 min). Both the sigmoid Emax and cubic polynomial transduction relationships were equally effective in describing the observed effect data and gave similar predictions. The proposed approach has the advantage of not assuming a specific compartmental structure for the pharmacokinetic-pharmacodynamic link. A particular advantage of the method is that no functional relationship is assumed a priori for the transduction relationship, and errors in both regression variables are considered in the optimization. The system analysis pharmacodynamic approach assumes linear disposition pharmacokinetics, an instantaneous and time invariant transduction, and that inductive effects like tolerance or sensitization do not develop significantly in the time frame studied. PMID- 8207681 TI - Synthesis of 6-(methoxycarbonyl)prednisolone and its derivatives as new antiinflammatory steroidal antedrugs. AB - The synthesis and pharmacological evaluation of 6-(methoxycarbonyl)prednisolone (11) (a 3:1 mixture of 6 alpha-isomer 11a and 6 beta-isomer 11b), its 21-ol acetates 13a (6 alpha-isomer) and 13b (6 beta-isomer), and 17,21-diol acetonide 14 (a 6:1 mixture of 6 alpha-isomer 14a and 6 beta-isomer 14b) as local antiinflammatory steroidal antedrugs are described. The lead compound 11 was prepared via 12 steps from hydrocortisone (1). In the croton oil-induced ear edema assay, the topical antiinflammatory activity of 13a was higher than that of its epimer 13b. Except for 13a, the compounds (11, 13b, and 14) showed less activity than prednisolone. The systemic activities were assessed after 5 days of consecutive administration of these compounds at equiactive doses. Neither 11 nor 14 depressed plasma corticosteroid levels or significantly altered adrenal weights. Thymic involution was absent for 14, 15% for 11, and 47% for prednisolone at the equiactive doses. Both 13a and 13b showed significant reduction of adverse systemic effects assessed as the increase of body weight and the decreases of adrenal and thymus weights. The putative metabolite, carboxylic acid 12, showed 26 times less topical antiinflammatory activity than prednisolone. These results suggest that introduction of a labile methoxycarbonyl group at the C-6 position of prednisolone results in retention of antiinflammatory activity while reducing systemic effects noted following topical application of the parent compound prednisolone. PMID- 8207682 TI - Correlation between monoamino oxidase inhibitor activity of some thiazol-2 ylhydrazines and their interaction with dipalmitoylphosphatidylcholine liposomes. AB - A calorimetric investigation has been carried out on the influence exerted by some 1-(alkoxybenzoyl)-2-(4-substituted thiazolyl-2-yl)hydrazines, possessing monoamine oxidase inhibitory (MAOI) activity, on the thermotropic behavior of model membranes constituted by dipalmitoylphosphatidylcholine (DPPC) vesicles. Attention was paid to evaluate how structural variations of drugs may influence drug-lipid interaction. The examined drugs were found to modify the gel to liquid crystal phase transition of DPPC liposomes, by causing a shift of the transition temperature (Tm) toward lower values and a negligible variation in the enthalpy changes (delta H). The different effects on DPPC thermotropic behavior of these MAOI drugs could be considered in terms of different substituents on the molecule's backbone. The calorimetric results were related to drug's MAO inhibitory activity measured by fluorescence techniques and the apparent distribution coefficient of the compounds in water/n-octanol. A hypothesis on a correlation between a drug's structure, inhibitory activity, and membrane interaction has been suggested. PMID- 8207683 TI - Hypolipidemic activity of 4-substituted 1,2-diacyl-1,2,4-triazolidine-3,5-diones in rodents. AB - A series of 4-substituted 1,2-diacyl-1,2,4-triazolidine-3,5-diones were synthesized and shown to be hypolipidemic in rodents; serum cholesterol and triglyceride levels were significantly reduced following intraperitoneal and oral dosing at 20 mg/kg/day. The hypolipidemic activity of the triazolidine-3,5-diones was improved when R1 was either a phenyl or a butyl group. Tissue lipid levels were reduced in the liver, aorta, and small intestine, while fecal lipids, e.g. cholesterol, were increased after 14 days. Very low density lipid cholesterol levels were reduced but high density lipid cholesterol levels were significantly increased. It appears that the mode of action of the 1,2-diacyl-1,2,4 triazolidine-3,5-diones is by the inhibition of the de novo rate limiting enzyme for lipid synthesis. Enzyme activities suppressed by the agents included ATP dependent citrate lyase, HMG CoA reductase, acyl CoA cholesterol acyl transferase, acetyl CoA carboxylase, sn-glycerol-3-phosphate aryl transferase, phosphatidylate phosphohydrolase, and cholesterol-7 alpha-hydroxylase. PMID- 8207684 TI - Aprikalim: radioimmunoassay and pharmacokinetic studies in mouse, monkey, and dog. AB - A stereoselective and specific radioimmunoassay (RIA) was developed for aprikalim (RP 52891), a novel potassium channel opener. Antibodies were produced in rabbits immunized with the pure levorotatory enantiomer (1R,2R) of the hapten derivative bearing an acid function at the end of the lateral chain and conjugated to bovine serum albumin. In displacement studies with the enantiomerically pure radioligand (radioiodinated tyrosine methyl ester conjugate of the hapten derivative), the opposite enantiomer showed only 0.1% cross-reaction. Negligible binding occurred when analogues or metabolites of aprikalim were tested for cross-reactivity. The detection limit was 0.25 ng/mL (9.31 x 10(-10) M) in a 20-microL plasma sample. The assay was used successfully to determine aprikalim pharmacokinetics in mice, monkeys, and dogs. Beagle dogs were given a 10 micrograms/kg intravenous (iv) bolus dose or 10 micrograms/kg iv bolus followed by 0.1 microgram/kg/min infused over 30 min (nonhypotensive doses which reduce myocardial infarct size significantly). The plasma concentrations declined monoexponentially with a mean overall elimination half-life of 1.53 h and a mean plasma clearance of 52 mL/min (5.1 mL/min/kg). A slow-release oral formulation produced a significant delay in the rate of absorption, a 4-fold decrease in the peak plasma level, and a 2-fold decrease in apparent oral bioavailability relative to that observed for an oral solution. A comparison of aprikalim pharmacokinetic parameters in mouse, monkey, and dog revealed great similarity in disposition characteristics in these species. PMID- 8207685 TI - Modification of the U.S.P. dissolution method for the analysis of norethindrone and ethinyl estradiol tablets. AB - A modification of the U.S.P. dissolution method for the quantitation of norethindrone and ethinyl estradiol tablets is proposed. This modification consists of the use of distilled water as the dissolution medium instead of 0.1 N hydrochloric acid (HCl) and/or neutralization of 0.1 N HCl with sodium carbonate prior to analysis. Statistical analysis of the results indicate that there are no significant differences between the dissolution in 0.1 N HCl and the dissolution in distilled water (p < 0.05) for norethindrone and ethinyl estradiol. PMID- 8207686 TI - Pharmacokinetics, safety, and tolerability of flosequinan in patients with hepatic dysfunction. AB - The pharmacokinetics of flosequinan and its active metabolite, flosequinoxan, were investigated following a single 100-mg oral dose in 10 patients with compromised hepatic function. Plasma and urine samples were collected for up to 144 h postdose and analyzed by HPLC. All 10 patients provided analyzable data even though one patient withdrew before the 144-h sample because of an adverse event unrelated to the study medication. Interpatient variability was appreciable for the plasma and urine concentrations was well as for the calculated pharmacokinetic parameters. Relative to a comparative cohort of normal subjects, flosequinan concentrations in the study patients were elevated, showing increases in mean AUC0-t (62.8 +/- 49.4 vs 3.4 +/- 1.5 micrograms.h/mL), AUC0-infinity (70.2 +/- 58.3 vs 3.8 +/- 1.6 micrograms.h/m:), Cmax (2.43 +/- 0.56 vs 1.30 +/- 0.39 micrograms/mL), and t1/2 (20.7 +/- 16.8 vs 1.7 +/- 0.5 h). The mean systemic clearance decreased (47.3 +/- 46.5 vs 544 +/- 279 mL/min), along with the elimination rate constant (0.066 +/- 0.069 vs 0.44 +/- 0.13 h-1). Mean flosequinoxan AUC0-t and AUC0-infinity values were unaffected by hepatic dysfunction. The mean time to peak was longer (36.4 +/- 27.4 vs 7.0 +/- 3.1 h) and Cmax was less (0.98 +/- 0.52 vs 1.84 +/- 0.26 micrograms/mL) than in normal subjects. These findings are consistent with a decrease in the rate of flosequinan metabolism to flosequinoxan. Five patients reported adverse events, which included headache (three patients) and syncope (one patient).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207687 TI - Determination of bioavailability and systemically available fractions of drugs undergoing reversible metabolism: application to 4-amino-5-chloro-2-[2 (methylsulfinyl)ethoxy]-N-[2- (diethylamino)ethyl]benzamide and its sulfide and sulfone metabolites in rats. AB - Methods are discussed which permit the calculation of the bioavailability (F) and fraction of an oral dose entering the central circulation (f) of a drug and its interconversion metabolite. The interrelationships between the F and f and between the F and systemically available fractions afforded by reversible metabolism are also derived and described. The application of these principles is illustrated by the pharmacokinetic analysis of 4-amino-5-chloro-2-[2 (methylsulfinyl)ethoxy]-N-[2- (diethylamino)ethyl]benzamide (ML-1035, 1) and its sulfide (2) and sulfone (3) metabolites in rats. Like intravenous ML-1035, ML 1035 administered orally underwent metabolic interconversion with 2 but not with 3 in this species. Both ML-1035 and 2 were absorbed rapidly and are pharmacologically active. On average, 8.3 and 13% of an oral dose (152.4 mumol/kg) of ML-1035 were bioavailable as ML-1035 and its sulfide metabolite, respectively, while 23 and 65% of a molar equivalent dose of the sulfide metabolite were bioavailable as either compound, respectively. Thus, the sulfide metabolite is better absorbed than ML-1035 in rats. Following oral administration of either ML-1035 or 2, the systemically available fractions of both compounds were weakly to moderately influenced by the reversible metabolism process in rats. Moreover, the bioavailability of the sulfone metabolite was very poor (2.5 4%) following separate oral administration of ML-1035, 2, and 3. PMID- 8207688 TI - gamma-Pyrone compounds. 5. Synthesis and antiplatelet effects of xanthonoxypropanolamines and related compounds. AB - A series of simple xanthonoxypropanolamines and related compounds were synthesized. 3-[3-(Cyclopropylamino)propoxy]-xanthone showed same potent antiplatelet effects as norathyriol tetraacetate on arachidonate-induced aggregation. 3-[3-(Cyclohexylamino)-2-hydroxypropoxy]xanthone showed more potent antiplatelet effects than norathyriol tetraacetate on collagen-induced aggregation. The various amino groups of the oxypropanolamine or oxypropylamine side chains of the synthesized compounds regulated the antiplatelet effects. PMID- 8207689 TI - Hydrophobic effect at the origin of the low solubility of inert solid substances in hydrogen-bonded solvents. AB - The new solubility equation derived from the thermodynamics of mobile order in liquids is used to predict the solubility of four solid aliphatic and aromatic hydrocarbons, namely, tricosane, octacosane, biphenyl and pyrene, in nonassociated and hydrogen-bonded solvents. The analysis of the relative importance of the different terms contributing to the solubility shows that (1) the fluidization of the solute always represents a barrier to the solubility, (2) in non-hydrogen-bonded solvents, the solubility essentially results from the balance of the exchange entropy correction and the change in the nonspecific cohesion forces upon mixing, (3) in alcohols or in water, the solubility is mainly determined by the hydrophobic effect which corresponds to a solute rejecting effect of the solvent. This effect is responsible for the lower solubility values of the inert substances in associated solvents with respect to those in nonassociated solvents. PMID- 8207690 TI - Antimicrobial properties of alkaloids from Xanthorhiza simplicissima. AB - The organic extract of the whole plant Xanthorhiza simplicissima was found to exhibit good activity against the AIDS-related opportunistic pathogens Candida albicans, Cryptococcus neoformans, and Mycobacterium intracellularae. Bioassay directed fractionation of the extract led to the isolation of the known alkaloid berberine as the major active component. A second alkaloid of the isohomoprotoberberine family, puntarenine, was isolated from this plant family for the first time. Puntarenine also showed marginal activity against the dermatophytic fungus Trichophyton mentagrophytes and the yeast Saccharomyces cerevisiae. PMID- 8207691 TI - Use of the triiodide-cetylpyridinium chloride micellar system for the determination of benzoyl peroxide in pharmaceutical preparations. AB - A kinetic spectrophotometric method for the determination of benzoyl peroxide in acne preparations is proposed. The method is based on the reduction of benzoyl peroxide by iodide in the cationic micellar medium provided by cetylpyridinium chloride (CPC). The triiodide ion produced associates with CPC micelles, which gives rise to an absorption maximum at 500 nm in addition to substantially increased absorptivity and stability constant for the triiodide complex. Acne preparations can be analyzed directly after dissolution of the samples in ethanol. The detection limit thus achieved is 0.033 microgram.mL-1, so the proposed method surpasses existing alternative methods in sensitivity. The relative standard deviation for 0.25 microgram.mL-1 is 2.1%. PMID- 8207692 TI - The extension grade: a model-unspecific rate characteristic derived from steady state plasma level fluctuations. AB - The rate aspect of bioavailability for pharmaceutical dosage forms in general and sustained-release preparations in particular can be quantified by an extension grade (EG), which is readily computed from steady-state data after administration of a test product and a suitable reference. Although the EG is unrelated to specific pharmacokinetic models or statistical moment analysis, interindividual differences of disposition kinetics are properly accounted for. It characterizes drug input in its entirety (i.e., the combination of drug release and absorption kinetics) and assumes values in the interval [0, 1]. Its properties resemble in several respects those of the area under the concentration versus time curve quotient F, which indicates the extent of bioavailability. The EG can be calculated from steady-state plasma levels and urinary excretion rates and from corresponding profiles observed after administration of single doses. It is easy to implement specific experimental designs for the determination of the EG. PMID- 8207693 TI - Quantitation of urinary 1,2,3,4-tetrahydro-beta-carboline and 1-methyl-1,2,3,4 tetrahydro-beta-carboline by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method was developed to quantify 1,2,3,4-tetrahydro-beta-carboline (TBC) and 1-methyl-1,2,3,4-tetrahydro-beta carboline (MTBC) in human urine. Urine samples with added internal standard were subjected to a reaction with fluorescamine and solvent extractions to remove the precursor tryptamine, which readily condenses with aldehydes in samples and reagents. Such a pretreatment completely suppressed the artifactual formation of TBC and MTBC during analytical procedures. The purified original tetrahydro-beta carbolines and the internal standard were separated by reversed-phase ion-pair chromatography with fluorescent detection. Their simultaneous separation was automatically completed in a short time (< 12 min). Both TBC and MTBC were quantified at ng/mL concentrations. The quantitative results revealed a wide variation in urinary levels of TBC and MTBC, possibly indicating that their considerable amounts excreted in the urine originate from dietary sources. PMID- 8207694 TI - Fourier-transform infrared spectroscopic studies of cross-linked human serum albumin microcapsules. 2. Influence of reaction time on spectra and correlation with microcapsule morphology and size. AB - Microcapsules were prepared from human serum albumin (HSA) through interfacial cross-linking with terephthaloyl chloride (TC). Reaction times were increased from 2 to 60 min, while pH (9.8) and TC concentration (2.5% w/v) were kept constant. Fourier-transform infrared (FT-IR) spectra of lyophilized microcapsules were compared. Correlations were established with microcapsule morphology and size, as had been done in a previous study exploring the effect of increasing pH values. Microcapsules obtained after 2 min had to be considered separately. Minor alterations were observed in the spectrum as compared with pure HSA. They consisted of a decrease of the ester-assigned 1724-cm-1 band and of the carboxylate-assigned 1394-cm-1 band, attributed to a removal of contaminating lipids of HSA, and an increase of the 1624-cm-1 band, attributed to interchain H bonding following acylation of the NH2 groups. Prolonging the reaction time resulted in a progressive increase of the bands at 1724 (esters), 1795 (anhydrides), and 1624 cm-1 (beta-sheet), in a further decrease of the 1394-cm-1 band (carboxylates), and in marked alterations of the 1340-1080-cm-1 region. These important changes, which appeared after 5 min, reflect the progressive acylation of the hydroxy and carboxylate groups of HSA. As in the previous series of pH-based assays, important spectral changes were shown to correspond to a decrease in microcapsule mean size (from 32 to < 15 microns) and in important modifications of the membrane surface, made rough. PMID- 8207695 TI - Quantitative structure-pharmacokinetic relationships for systemic drug distribution kinetics not confined to a congeneric series. AB - Many attempts have been made to describe quantitative structure-pharmacokinetic relationships within a congeneric series of drug molecules. The goal is to develop a predictive relationship that could predict in vivo results for other drugs within that series. These studies typically evaluate pharmacokinetic parameters that are reflective of both distribution and elimination processes. This work utilizes the results from 17 noncongeneric drugs reported in 18 pharmacokinetic studies. The objective was to determine if drug distribution parameters that were independent of elimination could be predicted from easily measured physicochemical parameters with a data base that included a wide variety of drugs that were not congeners of one another. Regression models utilizing a linear and a quadratic response surface were used to predict the various distribution parameters from physicochemical parameters, including molecular weight, intrinsic solubility, alcohol solubility, protein binding, and the distribution coefficient. Analogous to the extent of absorption, the extent of drug distribution can be predicted reasonably well by the probability that the drug will distribute into the peripheral system before being eliminated and by the volume of distribution at steady state. The duration of distribution, analogous to the rate of absorption, can be predicted by the mean transit time through the peripheral system the mean residence time of the drug in the peripheral system and the intrinsic mean residence time in the peripheral system. The ability to use statistical models to approximate drug distribution parameters without the constraints of working within a congeneric series provides some valuable opportunities. PMID- 8207696 TI - Sustained-release methotrexate for intracavitary chemotherapy. AB - Methotrexate was encapsulated into a lipid-based drug-delivery system to create a slow-release formulation (Depo/methotrexate) for intracavitary administration. Depo/methotrexate was stable in storage at 4 degrees C for > 4 months. In human plasma at 37 degrees C, the half-life of drug release was 40 days. After intraperitoneal injection of Depo/methotrexate in mice, the intraperitoneal apparent half-life of free methotrexate was 39.6 h, in contrast to a half-life of 0.5 h for the unencapsulated standard methotrexate (std/methotrexate). In L1210 murine leukemia model, the potency of a single dose of Depo/methotrexate was 334 fold higher, the increased life-span (ILS) was 2-fold greater, and the therapeutic index was 2-fold higher than a single dose of std/methotrexate. PMID- 8207697 TI - Quantitative structure-activity relationships of 5-lipoxygenase inhibitors. Inhibitory potency of pyridazinone analogues. AB - Quantitative structure-activity relationships (QSAR) of 72 1 phenyltetrahydropyridazin-3(2H)-one (I) analogues are examined for the inhibitory potency (IC50) of 5-lipoxygenase in a broken cell. The potency is increased by lipophilic substituents at the 3'- and 4'-positions. Substituents with positive F value at the 4'-position also increase the potency, while substituents at the 3' position with a positive R value decrease it. The potency also decreases as the size of the 2'- and/or 4'-substituents increases. Thioketone analogues are about 5 times more potent than the corresponding carbonyl analogues. PMID- 8207698 TI - A new attempt to solve the scale-up problem for granulation using response surface methodology. AB - Scale-up from lab to production is always problematic for the development of pharmaceuticals. In granulation, an optimal formulation of binder solution determined in a lab scale is often different than that in a production scale. A new mathematical procedure to solve this scale-up problem is assessed. Granules were prepared in the two manufacturing scales (2- and 5-kg scale) by using a high speed mixer granulator. In the manufacturing process, the binder solution plays an essential role in the formation of granules with desired physical properties, in close conformity with the manufacturing scale. A computerized optimizing technique based on a response surface methodology was developed to study the scale-up problem in the manufacturing of granules. For this purpose, a new mathematical function was introduced for the first time, which is namely an integrated optimization function. A universal optimal formulation unaffected by manufacturing scale could be obtained by minimizing the integrated optimization function. Predicted values such as yield, mean granule size, and uniformity of granule size agreed well with experimental ones on both scales. Furthermore, the optimized characteristics measured at the production scale coincided well with those obtained at laboratory scale, suggesting that this approach could be very useful in minimizing scale-up problems. PMID- 8207699 TI - Reduced inter- and intraindividual variability in cyclosporine pharmacokinetics from a microemulsion formulation. AB - The inter- and intraindividual variability of cyclosporine pharmacokinetics from a microemulsion formulation were compared with the currently marketed formulation in a sequential bioreplication study. Twenty-four healthy male volunteers were randomized to receive each formulation on two separate occasions; the reference treatment was a single oral dose of 300 mg of Sandimmune and the test treatment was a single oral dose of 180 mg of Sandimmune Neoral, both given as soft gelatin capsules. Serial venous blood samples were obtained over a period of 48 h after each administration, and cyclosporine concentrations were measured in whole blood by a specific monoclonal RIA method. Between- and within-subject variabilities were quantified from the appropriate sums of squares from analysis of variance and statistically compared between formulations. Both inter- and intraindividual variation for the peak concentration, time to reach the peak, area under the curve, and terminal half-life of the test formulation were significantly reduced (p < 0.05) with two exceptions. For area under the curve between subjects (p < 0.2) and peak concentration within subjects (p < 0.1), trends toward reduced variability for the test formulation were evident. These results were further reflected in the inter- and intraindividual coefficients of variation of the pharmacokinetic parameters that ranged from 3 to 22% for the test formulation compared with 19 to 41% for the reference formulation. In comparison with the currently marketed formulation, reduced variability in the pharmacokinetics of cyclosporine following oral administration of Sandimmune Neoral provides a more predictable and consistent concentration-time profile. PMID- 8207700 TI - A theoretical and experimental study of additive effects of physical aging and antiplasticization on the water permeability of polymer film coatings. AB - The effects of physical aging and antiplasticization on the water transport properties of glassy cellulose acetate film-coated tablets were investigated. The gradual approach toward thermodynamic equilibrium during physical aging decrease the free volume of the polymers. This decrease in free volume is accompanied by a decrease in the transport mobility, with concomitant changes in those properties of the polymer that depend on it. Antiplasticization arises from an interaction between the polymer and the plasticizer molecules and decreases the molecular mobility of the polymer and plasticizer. This effect was confirmed by mechanical measurements of polymer free films at the same experimental temperature. We have studied the additive effect of aging and antiplasticizing to see if the individual effects would interfere with one another, as might be expected if the same free volume were involved in each. The pronouncedly additive effects of physical aging and antiplasticization on the water permeability can be found in cellulose acetate film-coated tablets that were affected by longer physical aging time and lower plasticizer concentration. A theoretical study suggested that the free volume in the glassy polymer should consist of at least two independent parts, one of which is affected by annealing and the other by antiplasticization. PMID- 8207701 TI - In vitro evaluation of a controlled-release site-specific diisovaleryl tert butalone chemical delivery system for the eye. AB - Cellulosic polymers such as cellulose acetate (CA), cellulose acetate butyrate (CAB), and hydroxypropyl methyl cellulose phthalate (HPMCP) and hydrogels (hydroxyethyl/hydroxypropyl acrylate and hydroxypropyl methacrylate monomers) were used to sustain/control the release of diisovaleryl tert-butalone, a novel site-specific chemical delivery system (CDS) for potential antiglaucoma treatment. Diisovaleryl tert-butalone was incorporated into cellulosic polymers by the method of "solution casting" and into hydrogels by the method of "impregnation." In vitro release-rate kinetics from these systems were studied using a closed sink kinetic model. The release rate of CDS from the polymers chosen followed first-order kinetics and the release was sustained for about 2-6 h. In the case of hydrogels a pronounced "burst release" was observed. Increasing the percentage of cross-linker in the linear monomers of the hydrogel was shown to sustain the release longer. When the diisovaleryl tert-butalone CDS was incorporated into one of the cellulosic polymers, cellulose acetate butyrate, as the CDS-beta-cyclodextrin [heptakis(2,6-di-O-methyl)-beta-cyclodextrin] inclusion complex, the release pattern approximated Higuchi's expression for a monolithic matrix system, where the amount of CDS released from the polymer was proportional to the square-root of time. Further, the stability of the CDS in the polymer was improved when it was dispersed in the polymer as the CDS-beta-cyclodextrin CD complex. PMID- 8207702 TI - Application of accelerated testing to shelf-life prediction of commercial protein preparations. PMID- 8207703 TI - [Inhibitory effect of running exercise on age-induced muscle atrophy]. AB - The effects of a 10-week running exercise on the histochemical and morphological properties of muscle fibers in the soleus (SOL) and tibialis anterior (TA) muscles and also in spinal motoneurons were investigated in 4 groups of female rats. Animals of the control groups were 20, 90 and 100 weeks old. Animals of the experimental group were 100 weeks old, and were exercised on a running wheel for 10 weeks. Muscle fibers examined were classified as slow-twitch oxidative (SO), fast-twitch oxidative glycolytic (FOG) or fast-twitch glycolytic (FG) according to their contractile and metabolic profiles. Spinal motoneurons innervating the SOL and TA were identified by retrograde neuronal labelling of fluorescent dye, nuclear yellow. Oxidative enzyme activities of motoneurons in the neuron pool were examined by microspectrophotometry. When compared to 20 week old rats, a decrease in the number of FOG in the SOL and of FG in the TA was observed in 90 and 100 week old rats. Findings of atrophy were observed in SO and FOG of the SOL and in FOG and FG of the TA in 90 to 100 week old rats. Practically no changes were observed with aging in the number and oxidative capacity of motoneurons in the SOL neuron pool. However, a decrease with aging was observed in the number and oxidative capacity of motoneurons in the TA neuron pool. From these results it is indicated that exercise inhibits the age-induced atrophy of SO fibers in the SOL. PMID- 8207704 TI - Hand immersion as a method of cooling and rewarming: a short review. AB - Many cooling and warming procedures have been proposed for the treatment of hyperthermic or hypothermic individuals. One of the most recent of these is the use of hand immersion as a simple method to gain or lose heat. In the present paper the principles underlying this approach, and the evidence for and against hand rewarming/cooling, are briefly reviewed. It is concluded that hand immersion is likely to be more effective for cooling than rewarming individuals. PMID- 8207705 TI - Pre-medication of medical-risk patients for dental procedures. AB - The necessity to provide prophylactic antibiotic cover to avoid infective endocarditis for patients receiving dental treatment leads, on occasions, to confusion and is frequently the subject of questions at postgraduate meetings. There are several medical conditions which have in the past been considered to require prophylaxis which are no longer considered indications for such therapy. However, a definitive list of conditions necessitating antibiotic cover has been agreed (Table 1). There are several different schedules of prophylaxis which may be used in different circumstances. This paper seeks to identify the main features of infective endocarditis and current prophylactic schedules accepted in the United Kingdom. Figure 1 outlines, in the form of a flow-diagram, the decision making process involved in choosing the most appropriate schedule. This flow-diagram may act as a 'quick-reference' for use in the surgery. PMID- 8207706 TI - Neurophysiological monitoring of acute neurological decompression illness. AB - Somatosensory evoked potentials recorded over the scalp in response to posterior tibial nerve stimulation may provide a useful means of assessing the integrity of the neuraxis during the treatment of neurological decompression illness (DCI). The neurophysiological assessment of a case of DCI is described. PMID- 8207707 TI - Telemedicine: treating the patient by remote control. PMID- 8207708 TI - Diabetes care and the Royal Navy: the importance of a coordinated approach. AB - The provision of coordinated diabetic care with the establishment of a dedicated diabetic clinic at the Royal Naval Hospital Haslar, has improved the quality of life for the majority of service diabetics. The standard of diabetic control has improved greatly and there has been less sickness due to diabetes, though the effect on invalidings is inevitably less obvious. Good glycaemic control, a healthier lifestyle and a positive attitude, achieved through understanding diabetes and its implications, has been of overall benefit to the Royal Navy. PMID- 8207709 TI - MHC class II compatibility in aborted fetuses and term infants of couples with recurrent spontaneous abortion. AB - Maternal-fetal histocompatibility for alleles at HLA class II loci, HLA-DQA1 and HLA-DQB1, was examined in 40 abortuses and 31 liveborn children of 68 couples with a history of idiopathic recurrent spontaneous abortion (RSAB) who underwent leukocyte immunization prior to the index pregnancy. Significantly more couples with RSAB shared two HLA-DQA1 alleles as compared with fertile control couples (0.18 vs. 0.03, respectively; P = 0.031). There were no differences in HLA sharing between couples with RSAB who experienced a repeat abortion in the index pregnancy as compared with couples with RSAB who were delivered of a liveborn child. Non-significant deficits of abortuses who were compatible for alleles at the HLA-DQA1 (6 observed vs. 8.5 expected; P = 0.225) and the HLA-DQB1 (7 observed vs. 9.2 expected; P = 0.254) loci were observed. A significant deficit of HLA-DQA1 compatible liveborn children was observed (1 observed vs. 5.5 expected; P = 0.0069). The overall deficit of HLA-DQA1 compatible fetuses (7 observed vs. 14.0 expected; P = 0.0018) after approximately 8 weeks gestation suggests that HLA-DQA1 compatible fetuses may be aborted early in pregnancy, prior to the time when fetal tissue can be recovered for genetic studies. PMID- 8207710 TI - Elution of anticardiolipin antibodies and their cofactor beta 2-glycoprotein 1 from the placentae of patients with a poor obstetric history. AB - Anticardiolipin antibodies (aCL) were eluted from the placentae of four women with elevated serum levels of aCL, demonstrating that these antibodies are bound to affected placentae. Anticardiolipin antibodies bound to affected placentae were only of the IgG isotype and the level of aCL in placental eluates did not reflect serum levels. Anticardiolipin antibodies were not isolated from placental eluates of control normal pregnancies. beta 2-Glycoprotein 1, the anticardiolipin antibody cofactor, was present in the placental eluates from both control and antiphospholipid antibody (aPL) affected pregnancies and was localised in the syncytiotrophoblast by immunohistochemical analysis. Antinuclear antibodies were present in the placental eluates of 3 of the 4 patients with antiphospholipid antibody syndrome and were absent from the placental eluates of control pregnancies. The authors propose that anticardiolipin antibody binds directly to placental tissue, disrupting uteroplacental blood flow and/or transport through the villi. PMID- 8207711 TI - Identification of transforming growth factor-beta 1 mRNA in virgin and pregnant rat uteri by in situ hybridization. AB - Transforming growth factor-beta 1 (TGF-beta 1) has major effects on hematopoietic cell proliferation, migration and function. In an effort to learn whether or not TGF-beta 1 might be among the cytokines that influence uterine, placental and embryonic hematopoietic cells, in situ hybridization was used to map expression of the TGF-beta 1 gene through gestation in the rat. In cycling uteri, hybridization signals with a biotinylated TGF-beta 1 antisense RNA probe were comparatively weak and were restricted to myometrium. During pregnancy, TGF-beta 1 mRNA appeared in specific cell lineages in an ordered temporal sequence. In early post-implantation tissues (g.d. 5-8), TGF-beta 1 transcripts were prominent in uterine epithelial cells, muscle and decidual cells. At g.d. 15, hybridization signals were particularly strong in uterine epithelial cells, muscle and placental trophoblast cells. At this stage, TGF-beta 1 mRNA was also present in uterine cells resembling macrophages and in natural killer-like (GMG) cells. Steady state levels of specific message in uteri and placentas declined at late stages of gestation (g.d. 18, 21). In rat embryos, specific transcripts were identified at g.d. 9 and were prominently displayed in various types of embryonic cells from mid-gestation onwards. The results of this study are consistent with the postulate that throughout pregnancy in the rat, TGF-beta 1 may, in addition to its other functions, influence the proportions, patterns of distribution and activities of maternal and fetal hematopoietic cells. PMID- 8207712 TI - The effects of cytokines on human chorionic gonadotropin (hCG) production by a trophoblast cell line. AB - The present study was conducted to investigate the effects of cytokines on human chorionic gonadotropin (hCG) and its alpha- and beta-subunit release as well as protein synthesis in a trophoblast cell line. The human choriocarcinoma cell line, Jar, was used as a trophoblast model. Jar cells were incubated for 24 h with varying concentrations (5 x 10(-4)-40 micrograms/ml) of the following cytokines: Il-1, Il-2, Il-3, Il-4, Il-5, Il-6, IFN-gamma, tumor necrosis factor (TNF)-alpha, M-CSF and GM-CSF. Supernatants were assayed for hCG and its alpha- and beta-subunits by immunoradiometric methods. Cytotoxic effects were assessed by trypan blue staining. Protein synthesis was measured by [3H]leucine incorporation. The cytokines Il-1 and TNF-alpha significantly stimulated hCG release. The other cytokines had no significant effect on hCG production. Protein synthesis by the Jar cells was not significantly affected by either Il-1 or TNF alpha. However, IFN-gamma (40 micrograms/ml) significantly suppressed protein synthesis by the Jar cells. Trophoblast viability in the presence of TNF-alpha (10 micrograms/ml) and IFN-gamma (40 micrograms/ml) was only 40% and 50%, respectively. These results suggest that cytokines may be important regulators of trophoblast function. Il-I appears to have a stimulatory effect on trophoblast hCG release, while TNF-alpha and IFN-gamma appear to have cytotoxic effects on trophoblast cells. PMID- 8207713 TI - Activation of circulating gamma delta T-lymphocytes by autologous sperm from men sensitized to sperm. AB - The in vitro proliferative responses to sperm of T-lymphocytes bearing the alpha beta or gamma delta form of the antigen receptor were investigated. Peripheral blood mononuclear cells from five men without antisperm antibodies and eight men with antisperm antibodies both on sperm and in serum were incubated for 72 h in the presence of an equal concentration of autologous live sperm, freeze-thawed sperm and heat-killed sperm. Prior to incubation and after 72 h, aliquots were applied to Teflon coated microscope slides, which were subsequently incubated with monoclonal antibodies to the beta chain and delta chain of the human T-cell receptor. Urethral samples were cultured for bacteria and tested for Chlamydia trachomatis by direct staining and by ELISA. The four men with chlamydial infections had the highest concentrations of circulating gamma delta T-cells (P = 0.0008). The concentration of gamma delta T-cells from men with antisperm antibodies increased 245% over the buffer control in response to live sperm (P < 0.0001). Proliferation of gamma delta T-cells was also seen to a lesser extent in response to freeze-thawed (P = 0.002) and heat killed (P = 0.03) sperm. In contrast, gamma delta T-cells from men without antisperm antibodies proliferated only marginally (36%) in response to live sperm (P = 0.05) and were unresponsive to non-viable sperm. Only from men sensitized to sperm were alpha beta T-cells responsive, to a small extent, to live sperm (P = 0.04). Thus, in men with antisperm antibodies, peripheral gamma delta and alpha beta T-cells appeared to be sensitized to antigens on the surface of viable sperm. The immune response of gamma delta T-cells to sperm may be a useful in vitro system to examine the mechanism of gamma delta T-cell activation. PMID- 8207714 TI - Block in porcine gamete interaction by polyclonal antibodies to a pig ZP3 beta fragment having partial sequence homology to human ZP3. AB - A murine monoclonal antibody (MA-30) recognizing a sequential epitope on porcine zona pellucida-3 beta glycoprotein (ZP3 beta) and capable of inhibiting sperm-egg interaction was previously described. Polyclonal antibodies against a approximately 6 kDa fragment from the tryptic digest of ZP3 beta, reacting with MA-30, can also inhibit porcine gamete interaction in vitro. Partial N-terminal sequencing of the smallest fragment from the ZP3 beta tryptic digest having reactivity with MA-30 shows sequence homology with human ZP3. PMID- 8207715 TI - The treatment of empyema in childhood. PMID- 8207716 TI - Medical ethics and evolution. PMID- 8207717 TI - The genius of health. 7. Morals, music and medicine--Thomas Mann. PMID- 8207718 TI - The prevention and management of haemolytic disease of the newborn. PMID- 8207719 TI - The impact of the first 3 years of breast cancer screening on the overall presentation of breast cancer. AB - We have assessed the effect of the first round of the Breast Cancer Screening Programme on the presentation of breast cancer in the Southampton Health District with respect to number of cases and pathological characteristics. A retrospective comparative survey of the presentation of breast cancer in the 3 years prior to breast cancer screening (1985-1988) with the presentation of breast cancer during the prevalent round of breast cancer screening (1988-1991) was performed. During the period of study 1536 cases of breast cancer presented. Six hundred and sixty presented in the years prior to screening and 864 during the first round of screening. All patients lived within the Southampton Health District. The study was designed to assess the changes in breast cancer presentation with regard to age, pathological characteristics, and treatment. Even allowing for the increases in the local population there was a significant increase in the number of cases of breast cancer diagnosed (chi 2 = 23.7, df = 1, P < 0.001). The majority of this increase was in the 50-64 age group. There was also a significant shift towards an earlier stage at diagnosis and a significant reduction in tumour size when all cases were included (mean 26 mm versus 34 mm P < 0.001). Screening also created the opportunity for less invasive treatment. Consequently there was a rise in the number of excisions by localization biopsy from 1% to 13% during the screening period. In conclusion, the National Breast Cancer Screening Programme (NBCSP) has had a significant impact on the presentation of breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207720 TI - Reasons for rubella susceptibility among pregnant women in west Lambeth. AB - One hundred and thirty-three pregnant women who delivered at St Thomas' Hospital, in 1990 were noted to require rubella vaccination post partum. Fifty-three (39%) had completed a telephone questionnaire in order to determine reasons for susceptibility to rubella. Laboratory reports confirmed that 92 women were rubella seronegative and 27 had low levels of antibody. Of the 53 women interviewed, 25 gave a history of one or more rubella immunizations, 20 had no history of immunization and vaccination history was unknown for eight. Eleven of the 20 unvaccinated women had not been at school in the UK between 11 and 14 years of age. Eighty-seven per cent of the patients' general practitioners had no knowledge of their patients' rubella antibody status. Ninety-four per cent of the 133 women received rubella vaccine post partum. The Department of Health guidelines should be more vigorously implemented in order to identify and immunize remaining rubella susceptible women of child-bearing age. Susceptibility among women with a history of rubella immunization suggests that the seroconversion rate following rubella immunization in clinical practice may be lower than in vaccine trials. PMID- 8207721 TI - Wartime colon injuries: primary repair or colostomy? AB - A retrospective non-randomized study, comparing primary repair with colostomy, was made on a series of 102 patients with penetrating intraperitoneal colon injuries, in a war surgery programme in Cambodia. The overall case fatality rate (CFR) was 25.5%, whereas in the primary repair group CFR was 20%, compared to 30.8% in the colostomy group. The difference was not statistically significant (P = 0.30). Adjustment for possible confounding factors in the two groups did not alter the results. Considering the numerous advantages to the patient of a primary closure in the precarious situations where war surgery is often performed, this technique merits consideration. PMID- 8207722 TI - Hyperventilation in patients who have sustained myocardial infarction after a work injury. AB - Patients who present with acute myocardial infarction after a work injury (AMI WI) often report symptoms consistent with chronic hyperventilation which date back as far as the work injury itself, rather than to the AMI. The aim of the study was to test the hypothesis that hyperventilation significantly contributes to the symptoms of AMI-WI patients. The prevalence of hyperventilation was assessed by clinical capnography in 12 AMI-WI patients, 20 normal controls, 15 AMI patients whose AMI was conventional and not subsequent to a work injury (AMI C) and 14 patients with post-traumatic stress disorder (PTSD). End-tidal carbon dioxide partial pressure (P(et)CO2) was measured at rest, after 1 min hyperventilation (FHPT), after recall of the relevant stressor (Think) and when the breathing was felt to be normal (MBIN). P(et)CO2 levels after FHPT were: 29.0 +/- 1.5 (mean +/- SD) mmHg for AMI-WI; 26.7 +/- 1.9 mmHg for PTSD; 32.1 +/- 4.1 mmHg for AMI-C and 33.7 +/- 1.4 mmHg for the controls (P < 0.05 and P < 0.01 for AMI-WI and PTSD, respectively, versus controls). After Think, the levels were 25.8 +/- 1.6 mmHg for AMI-WI, 24.6 +/- 1.4 mmHg for PTSD, 31.2 +/- 4.1 mmHg for AMI-C and 31.2 +/- 1.5 mmHg for normals (P < 0.05 and P < 0.01 for AMI-WI and PTSD, respectively, versus controls). For MBIN, values of P(et)CO2 were 26.8 +/- 1.7 mmHg and 26.7 +/- 1.5 mmHg for AMI-WI and PTSD versus 33.8 +/- 1.2 mmHg for normals, (P < 0.01 for both versus controls).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207723 TI - Dogma and innovation in the global control of tuberculosis: discussion paper. PMID- 8207724 TI - Down's syndrome. PMID- 8207725 TI - Numbers and meaning: a dialogue in cross-cultural psychiatry. PMID- 8207726 TI - Robert Seymour Bridges OM: poet, physician and philosopher. AB - There has not been an English poet more interested in prosody nor physician more taken to medicine for its human contact, nor philosopher who lived closer to the tenets of his belief, than Robert Bridges (1844-1930). PMID- 8207727 TI - Huge bladder diverticula associated with Ehlers-Danlos syndrome. PMID- 8207728 TI - Complications of artificial hair implantation. PMID- 8207729 TI - Disseminated Trichosporon beigelii infection in an immunosuppressed child. PMID- 8207730 TI - How cold can you get? A case of severe neonatal hypothermia. PMID- 8207731 TI - Rectal tumour excision by transanal endoscopic microsurgery. PMID- 8207732 TI - Botulinum toxin. PMID- 8207733 TI - MRI as a single screening procedure for acoustic neuroma. PMID- 8207734 TI - Detection of laryngeal cancer. PMID- 8207735 TI - An INTERSALT study investigation: relationship between body mass index and blood pressure in the combined populations of three local centres in Japan. AB - Body mass index was positively and strongly correlated with BP in the INTERSALT study. Because the average body mass index in Japan, although low relative to other developed countries, has been increasing recently it would be useful, particularly from the public health viewpoint, to investigate the impact of body mass index on BP in Japanese populations. In this study, the relationship between body mass index and BP was investigated taking into account age, alcohol intake and sodium and potassium excretion in 24h urine. Data were obtained from 274 men and 284 women, aged 20-59 years, who were not taking antihypertensive medication. Random selection of participants took place at three local centres as outlined in the 1985 INTERSALT study in Japan. It was found that body mass index was positively and significantly correlated with BP in men and women, respectively, but was independent of age, alcohol intake and urinary sodium/potassium ratio. Both SBP and DBP were significantly higher by > or = 5 mmHg in participants whose body mass index (kg/m2) was in the highest quartile compared with participants in the lowest or the next lowest quartile category in men and women. In this study, it was suggested that the body mass index in Japanese men and women was directly correlated with BP independent of other confounding factors. Accordingly, the maintenance of a moderate body mass index may be important in achieving and maintaining a desirable BP level. PMID- 8207736 TI - Variation of within visit blood pressure readings at a single visit in the elderly and their relationship to ambulatory measurements. AB - The value of routinely taking one or several BP readings at a single visit in subjects with an initially elevated BP reading is unclear. The variation of sequential BP readings in the elderly, who often have a disproportionate increase in SBP compared with DBP, has received little attention. In addition, no attempt has been made to relate the various BP readings obtained to a subject's ambulatory daytime BP. The aim of this study was to examine the variation in BP between one, two or three readings at a single visit in elderly subjects with elevated BPs and to compare these readings with those obtained from daytime ambulatory BP monitoring (ABPM). Sixty-nine subjects, mean age 76 years (range 66 86 years) with at least one SBP reading > 150 mmHg and who had undergone a minimum of two previous clinic visits for BP measurement by the same physician were included. Following five minutes rest three supine BP readings were taken, spaced two minutes apart, using a Hawksley random zero sphygmomanometer. Seventeen subjects underwent home 24h ABPM commencing immediately after the clinic BP readings. Clinic SBP fell from first to third reading by 11 mmHg (95% Cl 9-13 mmHg, P < 0.001) and from first to second readings by 6 mmHg (Cl 4-8 mmHg, P < 0.01). There was no change in mean DBP between readings. In 85% of readings first SBPs were higher than the second.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207737 TI - Relationship between abnormal regulation of cytoplasmic calcium and elevated blood pressure in patients with primary hyperparathyroidism. AB - Primary hyperparathyroidism (HPT) is characterised by a defective calcium sensitivity of the parathyroid glands. HPT is, furthermore, associated with a high prevalence of hypertension. In the present study BP was measured before operation, during surgery and after operation in 42 HPT patients and in 15 control subjects operated for non-toxic goitre. Parathyroid tissue was removed from all patients and the concentration of cytoplasmic calcium [Ca2+]i was determined in vitro in dispersed single cells by means of microfluometry at extracellular calcium concentrations of 0.5 mM and 3.0 mM. The SBP levels were found to be raised both before (158 +/- 23 (SD) mmHg vs. 144 +/- 24 mmHg in controls, P < 0.05), during surgery (maximal level 167 +/- 22 mmHg vs. 146 +/- 16 mmHg in controls, P < 0.01) and after operation (maximal level 180 +/- 26 mmHg vs. 148 +/- 20 mmHg in controls, P < 0.001) in the HPT subject when compared with controls. SBP during surgery was found to be related to the in vitro measured [Ca2+]i in the parathyroid cells at 3.0 mM extracellular calcium concentration or to the ratio of [Ca2+]i at 3.0 mM-0.5 mM (r = -0.25 and -0.27, respectively; P < 0.05). The degree of suppression of PTH release in vitro at 3.0 mM extracellular calcium was found to be related to both systolic and diastolic BP (r = 0.57 and r = 0.53, respectively; P < 0.05) before surgery. In conclusion, BP was found to be raised in HPT patients both before operation as well as during surgery and after operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207738 TI - Relationship between increased blood pressure and hypoalgesia: additional evidence for the existence of an abnormality of pain perception in arterial hypertension in humans. AB - An association between hypertension and decreased pain perception (hypoalgesia) has been shown in experimental hypertension and confirmed in humans by electrical tooth pulp stimulation. The aim of this study was to confirm, using two other techniques, whether hypertension is associated with hypoalgesia in humans. In 77 untreated essential hypertensive outpatients, 37 normotensive outpatients and 27 normotensive volunteers subjective cutaneous sensitivity was assessed by an electrical stimulator. Thirty-three measurements were repeated after one month. In addition, in eight normotensive volunteers and eight hypertensives the thresholds of the polysynaptic components R2 and R3 of the blink reflex to electrical stimulation of the supraorbitalis nerve were evaluated. Tooth pulp stimulation was done in 85 of the subjects who measured cutaneous sensitivity and in all of the blink reflex study. Cutaneous perceptive, pain and tolerance thresholds were significantly higher in the hypertensives compared with both normotensive groups, with no significant difference between these two. The results were identical when age and sex-matched subgroups were compared and a high reproducibility was found for all three parameters. Similar findings were obtained for the tooth pulp thresholds and highly statistically significant correlations were found between cutaneous and tooth pulp sensitivity and between these indices and blood pressure. The thresholds of R2 and R3 were also significantly higher in the hypertensives and a significant correlation was found between R3 threshold and diastolic pressure. These results confirm that hypertension is associated to hypoalgesia in humans. PMID- 8207739 TI - Time dependency of the antihypertensive efficacy of the new renin inhibitor Ro 42 5892. AB - The objective of this study was to assess the antihypertensive efficacy of the new renin inhibitor Ro 42-5892 in patients with essential hypertension treated with 100 mg once daily orally. This was a double-blind, placebo-controlled, parallel group trial. After three weeks of wash-out and one week of single-blind placebo run-in periods, 25 patients with mild to moderate essential hypertension (sitting DBP between 95 and 114 mmHg) were randomised to receive either placebo (n = 12) or 100 mg of Ro 42-5892 (n = 13) once daily for eight days. On the eighth day, four hours after the oral administration, patients were randomised to receive intravenously either placebo or 10 mg of Ro 42-5892. BP and heart rate were measured repeatedly (hourly for eight hours and at the 24th hour post-dose) on the first and last days of active treatment. Compared with the placebo group, a slight decrease in sitting DBP was observed after the first dose in the Ro 42 5892 group. The decrease in sitting DBP reached significant levels only at six to eight hours post-dosing. In contrast, on the last day of active treatment, a larger, faster and longer decrease in sitting DBP was observed in the Ro 42-5892 group. Thus, the peak effect (-8.9 +/- 1.9 vs. -2.9 +/- 1.3 mmHg, P < 0.01) was reached 1.5 hours post-dosing and the trough effect (24 hours post-dosing) was slightly but significantly lower when compared with the placebo group (-3.0 +/- 1.0 vs -0.3 +/- 0.8 mmHg, P < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207740 TI - Comparison of cilazapril and nifedipine retard on ambulatory blood pressure, metabolic, rheological and platelet function in hypertensive patients. AB - In a 12 week randomised, double-blind study, a total of 31 patients with a sitting DBP of between 95 and 115 mmHg were enrolled for comparison of the antihypertensive, metabolic and antiplatelet effects of the drugs cilazapril and nifedipine retard. A two week placebo treatment was given before either cilazapril (2.5 mg daily) or nifedipine retard (20 mg twice daily) was administered. After four weeks treatment, those patients with a sitting DBP > 90 mmHg were given a doubling of their initial doses for the next six weeks; the others were maintained at their initial doses. All patients received their drugs and reported any adverse effects every other week. Blood was taken for metabolic, rheological and platelet function tests. Ambulatory BP and heart rate were recorded at the start, fourth and tenth weeks of study. At the end of this trial, there was a significant decrease in both SBP and DBP in the cilazapril group (155 +/- 14 to 142 +/- 12 mmHg systolic, P < 0.01; 106 +/- 6 to 95 +/- 5 mmHg diastolic, P < 0.01). In the nifedipine group, there was also a significant decrease in SBP and DBP (161 +/- 18 to 139 +/- 5 mmHg, systolic, P < 0.01; 101 +/ 6 to 88 +/- 9 mmHg diastolic, P < 0.05) but with a significant increase in heart rate (79 +/- 14 to 91 +/- 10 beats/minute, P < 0.05). There were no significant changes in the biochemical or metabolic parameters in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207742 TI - Discrepancies between clinic and ambulatory BP measurements. PMID- 8207743 TI - The history of blood pressure measurement. PMID- 8207741 TI - Perindopril plus nifedipine versus perindopril plus hydrochlorothiazide in mild to severe hypertension: a double-blind multicentre study. The Multicentre Study Group on Treatment Association with Perindopril. AB - Thiazide diuretics are considered as the choice drug to combine with ACE inhibitors for the treatment of hypertension. However, there is much evidence showing that the combination of ACE inhibitors with a calcium channel blocker is effective and safe. We compared the safety and efficacy of perindopril 8 mg once daily plus nifedipine SR 10 mg twice daily with perindopril 8 mg once daily plus hydrochlorothiazide (HCTZ) 12.5 mg once daily in a two phase three month study. After a one month placebo run-in period, patients whose DBP averaged 95-125 mmHg received perindopril 4 mg once daily for the first open phase (n = 524). After one month those whose DBP remained > 90 mmHg were prescribed perindopril 8 mg once daily for a second month. Among them, those whose DBP were still > 90 mmHg entered the second phase for one month, in a double-blind fashion. Fifty-three patients received HCTZ (BP: 161.2/99.2 +/- 2.0/0.9 mmHg), 57 received nifedipine (BP: 161.4/98.7 +/- 2.2/0.7 mmHg). Five patients withdrew due to side-effects, three patients in the perindopril plus nifedipine group and two in the perindopril plus HCTZ group. After one month there was a significant drop in BP (P < 0.01) in both groups: perindopril plus HCTZ (-13.9/-11.9 mmHg) and perindopril plus nifedipine (-12.1/-10.8 mmHg). Heart rate was not significantly modified: perindopril plus HCTZ (-1.30 beats/min), perindopril plus nifedipine (+0.54 beats/min). There were no significant difference between the two combinations for BP reduction and heart rate. The incidence of adverse experiences was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207745 TI - Relative risk of untreated hypertension in type-A employed African American women. AB - The purpose of this study was to determine the relative risk of hypertension in African American women with type A behaviour pattern. Of the 305 employed African American women, 147 (48.2%) were classified as type A and 158 (51.8%) as type B. The logistic regression procedure was used to calculate the adjusted relative risk of having an elevated SBP by controlling for age, weight and cholesterol. We found that the adjusted relative risk of type A African American women having an elevated SBP and DBP was 9.06 and 2.26 times that of type B, respectively. PMID- 8207744 TI - Effect of verapamil on reinfarction and cardiovascular events in patients with arterial hypertension included in the Danish Verapamil Infarction Trial II. The Danish Study Group on Verapamil in Myocardial Infarction. AB - An increased incidence of reinfarction and cardiovascular events has been reported in patients with hypertension recovering from acute myocardial infarction. We studied the effect of intervention with verapamil on the development of myocardial infarction and cardiovascular events in 301 patients with hypertension enrolled in the Danish Verapamil Infarction Trial II. During the second week after the index infarct, patients were randomly assigned to treatment with verapamil 360 mg per day (n = 149) or placebo (n = 152) and followed-up to 18 months (mean 16 months). The 18 months first reinfarction rates were 12.5% in verapamil and 19.8% in placebo treated patients (hazard ratio 0.53, 95% confidence limits 0.28-1.00, P = 0.04). The first cardiovascular event rates were 21.8% in the verapamil and 29.3% in the placebo group (hazard ratio 0.66, 95% confidence limits 0.41-1.06, P = 0.07). In this retrospective analysis of patients with hypertension included in the Danish Verapamil Infarction Trial II, intervention with verapamil reduced cardiovascular events primarily due to a substantial reduction in reinfarctions. PMID- 8207746 TI - Proceedings of the Pathological Society of Great Britain and Ireland. 169th Meeting of the Society. July 6-8, 1994. Abstracts. PMID- 8207747 TI - Monomeric collagen imaged by cryogenic force microscopy. PMID- 8207748 TI - LIP-model-based three-dimensional reconstruction and visualization of HIV infected entire cells. AB - This paper presents a global solution from acquisition to visualization for the three-dimensional reconstruction of cell sections. Original techniques are proposed for the correct handling of geometrical section distortions, and a new interpretation based on the logarithmic image processing (LIP) model is applied in order to create normalized grey-level sections where these are missing. Finally, a new method for generating a mesh of triangles to describe the envelope of the reconstructed cell is proposed, as well as a visualization mixing image synthesis and grey-level information. The product allows the user to explore the reconstructed cellular block in any desired direction, by showing user-defined grey-level sections inside the block mixed to a synthetic view of the cell envelope. PMID- 8207749 TI - A simple method for processing individual oocytes and embryos for electron microscopy. AB - A simple method for handling individual specimens that must be processed either for scanning or transmission electron microscopy studies is described. For scanning microscope processing, dehydration is carried out with samples enclosed in small cages made from TAAB capsules in which top and bottom are substituted by plankton nets, and for transmission electron microscopy, samples are preembedded in agarose. This procedure significantly reduces mouth pipetting, dissecting microscope observations, is less labour intensive and, most importantly, reduces sample loss. PMID- 8207750 TI - Metal-induced developmental toxicity in mammals: a review. AB - It is well established that certain metals are toxic to embryonic and fetal tissues and can induce teratogenicity in mammals. The main objective of this paper has been to summarize the toxic effects that excesses of certain metals may cause on mammalian development. The reviewed elements have been divided into four groups: (a) metals of greatest toxicological significance (arsenic, cadmium, lead, mercury, and uranium) that are wide-spread in the human environment, (b) essential trace metals (chromium, cobalt, manganese, selenium, and zinc), (c) other metals with evident biological interest (nickel and vanadium), and (d) metals of pharmacological interest (aluminum, gallium, and lithium). A summary of the therapeutic use of chelating agents in the prevention of metal-induced developmental toxicity has also been included. meso-2,3-Dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercaptopropane-1-sulfonate (DMPS) have been reported to be effective in alleviating arsenic- and mercury-induced teratogenesis, whereas sodium 4,5-dihydroxybenzene-1,3-disulfonate (Tiron) would protect against vanadium- and uranium-induced developmental toxicity. PMID- 8207751 TI - Evaluation of the humoral immune response of CD rats following a 2-week exposure to the pesticide carbaryl by the oral, dermal, or inhalation routes. AB - The objective of this study was to examine the immunotoxicological effects of the methyl-carbamate pesticide carbaryl via the oral, dermal, or inhalation routes. Male CD rats were exposed to carbaryl 5 d/wk for a 2-wk period. During nose-only inhalation exposures, rats received either 36, 137, or 335 mg/m3 carbaryl in acetone for 6 h. Air only and acetone/air controls were run concurrently. Orally exposed animals received either 1 ml corn oil or 10, 25, or 50 mg/kg carbaryl, while dermally exposed animals received either 2 ml acetone or 100, 500, or 1000 mg/kg carbaryl on their dorsal flank for 6 h. Four days prior to sacrifice, animals from all exposure groups were injected iv with 2 x 10(8) sheep red blood cells (SRBC). The primary immunoglobulin M (IgM) humoral immune response to SRBC was then assessed by measuring SRBC-specific antibody-forming cells (AFC) and levels of serum anti-SRBC IgM antibody, respectively, using the hemolytic plaque assay and an enzyme-linked immunosorbent assay. Individual body weights, spleen, thymus, and liver weights, spleen cell number, and red and white blood cell (RBC, WBC) counts were obtained for each animal. Following nose-only inhalation exposures, dose-dependent decreases in thymus weights, spleen cell number, AFC/spleen, AFC/10(6) splenocytes, and serum levels of SRBC-specific IgM antibody were observed. Significant decreases of 33, 57, and 22% in spleen cell number, AFC/spleen, and thymus weight, respectively, were found at the 335 mg/m3 exposure level. Animals exposed orally to 25 mg/kg carbaryl had a 34% decrease in WBC counts. A 34% decrease in WBC and a 13% increase in RBC counts were observed at the 50 mg/kg oral dose. Significant decreases in liver weights ranging from 11 to 13% were found at all oral exposure levels. Dermal exposure to carbaryl revealed no significant toxicological effects. Results indicate that humoral immune suppression was observed following inhalation, but not following oral or dermal exposures to carbaryl. Immunotoxicological studies evaluating pesticides need to consider relevant exposure routes and dosages for appropriate risk assessment procedures and exposure limits to be established. PMID- 8207752 TI - Congener-specific determination of polychlorinated biphenyls and organochlorine pesticides in human milk from Norwegian mothers living in Oslo. AB - Human milk samples from 28 mothers at Oslo City Hospital, Norway, were collected in 1991 and analyzed for individual polychlorinated biphenyl (PCB) congeners, IUPAC numbers 28, 74, 99, 101, 105, 114, 118, 128, 138, 141, 153, 156, 157, 170, 180, 194, and 206, plus selected non-ortho-substituted compounds, IUPAC numbers 77, 126, and 169. Sum DDTs (sum of concentrations of DDT and related compounds), hexachlorobenzene (HCB), oxychlordane, transnonachlor, and sum hexachlorocyclohexanes (HCHs) (sum of concentrations of alpha-HCH, beta-HCH, and gamma-HCH) were also determined. The mean levels of sum DDTs, HCB, oxychlordane, transnonachlor, and sum HCHs were 338, 41, 9, 19, and 36 ng/g, respectively, in human milk fat. p,p'-DDE and beta-HCH accounted for 81 and 93% of sum DDTs and sum HCHs, respectively. The mean level of sum PCBs (sum of mean concentrations of 20 individual congeners) was 372 ng/g milk fat. A very good correlation was found between sum PCBs and PCB-153 (r = .97). Sum PCBs determined on a capillary column was found to account for 62-79% of total PCBs calculated by using the packed column method used in previous human milk surveys in Norway. Comparison with previous results revealed that the mean sum PCB, HCB and sum DDT levels were decreased by 70, 65, and 75%, respectively during the past 9 yr. The contribution of individual PCDD/PCDF (earlier Norwegian study) and non- and mono-ortho substituted PCB congeners to the total calculated toxic equivalent values was assessed, and the PCBs were found to constitute a major part of the TCDD equivalents in human milk, with PCB-126 as the main contributor. PMID- 8207754 TI - Manganese toxicity: muscarinic receptor binding in the mouse brain. AB - In the present study we determined the effect of repeated administration of manganese chloride on the binding parameters of [3H]quinuclidinyl benzilate (3H QNB) in striatum, frontal cortex, and hippocampus of mice. Daily intraperitoneal injections of manganese chloride (5 mg Mn/kg) 5 d/wk during 9 wk did not alter the receptor density (Bmax) and the dissociation constant (Kd) of 3H-QNB in the different brain regions studied. These results suggest that chronic treatment with manganese does not affect the binding characteristics of 3H-QNB to the cholinergic muscarinic receptors in mouse brain. PMID- 8207753 TI - Effects of fasting and 3,3',4,4',5,5'-hexabromobiphenyl on plasma transport of thyroxine and retinol: fasting reverses elevation of retinol. AB - Male Wistar rats were injected ip with 0 or 20 mg/kg 3,3',4,4',5,5' hexabromobiphenyl and blood samples were collected 1, 3, 6, 7, and 8 d later. At 8 d after the injection, serum retinol was increased 30% and serum thyroxine was decreased 26% relative to control values. These effects were apparently unrelated to transthyretin in that the biphenyl did not alter the proportion of thyroxine binding in vitro to the prealbumin fraction of serum proteins. Separate groups of control and HBBP-injected rats did not receive food on d 7 (i.e., 24-h fast) and d 8 after injection (i.e., 48-h fast). Fasting decreased the serum retinol and thyroxine concentrations as well as the proportion of thyroxine binding in vitro to the prealbumin fraction of serum. The decreases in retinol and thyroxine concentrations associated with fasting are therefore ascribed to a decrease in the concentration of transthyretin in circulation. PMID- 8207755 TI - Effect of chlorpromazine pretreatment on cadmium toxicity in the male Wistar (WF/NCr) rat. AB - A recent report has indicated that cadmium-induced testicular damage in CF-1 mice can be prevented by pretreatment with calmodulin inhibitors such as chlorpromazine (CPZ), trifluoperazine, or N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7). However, the basis of this tolerance to cadmium is unclear and has not been demonstrated in any species other than mice. Thus, we examined the effects of the calmodulin inhibitor CPZ on cadmium toxicity in male Wistar (WF/NCr) rats. A single sc injection of 25 mumol CdCl2/kg proved nonlethal over 24 h but caused the typical spectrum of testicular lesions and increases in hemoglobin content (as assessed by hemoglobin absorbance in testicular supernatant). Pretreatment with 40 mumol CPZ/kg had no effect on cadmium-induced testicular lesions but did reduce testicular hemoglobin content, while 120 mumol CPZ/kg moderately reduced the severity of testicular lesions and hemoglobin contents. CPZ pretreatment in some cases increased cadmium content in liver and reduced testicular content but had no effect on renal levels. Cadmium treatment markedly increased hepatic and renal metallothionein (MT), a metal-binding protein often associated with tolerance to cadmium. CPZ alone likewise increased hepatic MT and MT mRNA, but did not modify renal MT, renal MT mRNA, or testicular MT mRNA. In contrast to liver and kidney, testicular cadmium-binding protein (TCBP) decreased in rats exposed only to cadmium or to CPZ, while CPZ pretreatment had no further effect on cadmium-induced reductions in TCBP levels. These results indicate that, like mice, CPZ in rats can reduce the testicular toxicity of cadmium as indicated by CPZ-induced reductions in testicular vascular lesions and hemoglobin contents. However, in rats CPZ has a less dramatic effect on such cadmium-induced lesions than in mice. The CPZ-induced stimulation of hepatic MT gene expression or modification of toxicokinetics may both play roles in this acquired tolerance to cadmium. PMID- 8207756 TI - Fungal metabolism of 3-nitrofluoranthene. AB - We investigated the metabolism of 3-nitrofluoranthene by filamentous fungus, Cunninghamella elegans ATCC 36112. Cunninghamella elegans metabolized about 72% of the 3-nitro[3,4-14C]fluoranthene added during 144 h of incubation to 2 major metabolites. These metabolites were separated by reversed-phase high-performance liquid chromatography and identified as 3-nitrofluoranthene-8-sulfate and 3 nitrofluoranthene-9-sulfate by 1H nuclear magnetic resonance, UV-visible, and mass spectral techniques. These results, in conjunction with previous studies on the fungal metabolism of fluoranthene, indicate that the nitro substituent at the C-3 position of fluoranthene sterically hinders epoxidation and shifts metabolism to the C-8 and C-9 positions. Since the phenolic microsomal metabolites of 3 nitrofluoranthene are mutagenic, the formation of sulfate conjugates of 8- and 9 hydroxy-3-nitrofluoranthene by C. elegans suggests that the fungal metabolic pathways may be beneficial for detoxification of this ubiquitous pollutant. PMID- 8207757 TI - Risk of benzene-induced leukemia: a sensitivity analysis of the pliofilm cohort with additional follow-up and new exposure estimates. AB - This report updates the risk assessment by Crump and Allen (1984) for benzene induced leukemia that was used by OSHA (1987) to support its reduction of the permissible exposure limit (PEL) to 1 ppm and that also was the basis for EPA's (1985) interim "unit risk" for benzene. The present study derives new risk estimates using data from follow-up through 1987 (whereas the earlier assessment only had follow-up available through 1978), and using new exposure estimates for this cohort developed by Paustenbach et al. (1992) that account for a number of factors that were unknown or not fully evaluated in earlier exposure assessments. There was a significant excess of acute myelocytic or acute monocytic leukemia (AMML, the only forms of acute nonlymphatic leukemia observed) in this cohort, and this end point also exhibited a strong dose-response trend. AMML was the only hematopoietic or lymphatic cancer that was clearly linked to benzene exposure. However, quantitative estimates of risk based on modeling either AMML or all leukemia differed by only 20%. Differences between the two Pliofilm plant locations in the occurrence of AMML were not statistically significant (.12 < or = p < or = .21) after differences in levels of benzene exposure were taken into account. The Paustenbach et al. exposures predicted a quadratic dose response, based on a measure of exposure that weighted intensity of exposure more heavily than duration of exposure. The best-fitting quadratic models predicted an additional lifetime risk of a benzene-related death from 45 yr of exposure to 1 ppm of between 0.020 and 0.036 per thousand. Statistical confidence intervals (90%) on these estimates were barely wide enough to include risk estimates based on linear dose response models. These linear models predicted risks of between 1.6 and 3.1 per thousand. PMID- 8207758 TI - Statistical analytical methods for comparing the incidence of tumors to the historical control data. AB - Statistical analysis for comparing the incidence of tumors in treated groups to historical control data is not generally performed. In the present study, a number of data exhibiting the lowest, low, moderate and highest incidence of tumors from long-term rodent bioassay studies has been compared with the historical control data. In studies exhibiting the lowest incidence (less than a few percent) of tumors, the Kastenbaum and Bowman test was found to be relevant since it takes into account the sample size of both the historical control data base and each treated group in the study. In studies where a wider range of tumor incidence was exhibited, a statistical method which employs a rejection limits based on the range of incidence in the historical data is recommended. When malignant tumors are evident in treated groups, no matter how low the incidence, they should be analyzed statistically and compared with the incidence in historical control data as well as those in the concurrent control group. Statistical analytical comparisons of study results to historical control data may contribute to more meaningful evaluations in carcinogenicity studies by eliminating possible false positive or false negative results. PMID- 8207759 TI - Acute toxicity of braxin C, a bracken toxin, in guinea pigs. AB - Braxin C (BC), ptaquiloside, is a toxin isolated from bracken fern. In order to determine the characteristics of the acute BC toxicity, BC was administered as a single subcutaneous (s. c.) injection to guinea pigs, rats, and mice. BC (5 and 10 mg/kg) induced hemorrhagic cystitis and hematuria in guinea pigs, whereas no changes were observed in rats and mice administered BC at a dose of 100 mg/kg. In guinea pigs administered BC (5 and 10 mg/kg), marked edema and hemorrhage were noted in the lamina propria of urinary bladder, though these inflammatory changes were also observed in the tissues such as perirenal adipose tissues or abdominal wall. These findings clearly demonstrate that BC is a potent toxin capable of inducing hemorrhagic cystitis in guinea pigs, and suggest that it is one of the toxic principles responsible for bracken poisoning. PMID- 8207760 TI - A simple method for screening assessment of skin and eye irritation. AB - A stepwise, simple screening test for skin and eye irritations, suitable for industrial chemicals or pesticides which are not required to be examined for their exact potential irritancy levels, was developed. The efficacy of the test was evaluated using 15 chemicals including typical irritants (acetic acid, ammonia, chloroacetic acid, dioxane, ethanolamine, formaldehyde, formic acid, hydrogen peroxide, phenol, phosphoric acid, propionic acid, sodium hydroxide, sodium hypochlorite, sulfuric acid, and trichloroacetic acid). Chemicals were chosen so as to represent irritants which act by different mechanisms (i.e., strongly acidic, alkaline, reactive to protein, oxidizing etc.). The method consisted of physicochemical tests and animal tests using rats, mice or guinea pigs, namely, a skin irritation test, an intradermal reaction test and an eye irritation test in a sequential manner such that further tests are not required if a positive result is obtained in earlier steps. Results obtained between two laboratories using this method were very similar. Comparison of our results with the data obtained by the conventional method using rabbits showed fairly good coincidence. The method was shown to be useful in assessing skin and eye irritation of chemicals and causes minimal suffering to animals. PMID- 8207761 TI - Inter-laboratory validation study of the Skin2 Dermal Model ZK1100 and MTT cytotoxicity assay kits. AB - An inter-laboratory validation study was conducted to evaluate the potential of 4 chemicals to cause irritation with utilizing the Skin2 Dermal Model ZK1100 kit developed by Advanced Tissue Sciences, Inc. (formerly Marrow-Tech, Inc., La Jolla, California, USA). The chemicals tested were sodium dodecyl sulfate (SDS), 1-n-hexadecyl-pyridinium chloride monohydrate (CC), ethanol (EtOH), and dimethyl sulfoxide (DMSO). Eleven Japanese institutions participated in this validation research to evaluate the usefulness of the Skin2 Model ZK1100 kit in accordance with an identical protocol. None of the participating laboratories had previously used the Skin2 Model ZK1100 kit. The MTT-50 value obtained in the individual institutions was 42 to 91 micrograms/ml for SDS, 2.7 to 8.6 micrograms/ml for CC, 2.0 to 9.3% for EtOH, and 11.5 to 21.9% for DMSO. Reproducibility was reasonably good as noted when one test chemical was repetitively tested by the same investigator. MTT-50 values obtained with the present method correlated with DS20 values obtained with Draize's method (r = 0.9881) in one of the participant institutions. The irritation study using the Skin2 Model ZK1100 kit was easy to perform and generated quantitative data. When the test was repeated, reproducibility was demonstrated with a variation of less than 2 sigma. These data suggested that this newly developed in vitro method would be useful in toxicity screening studies in terms of both time and cost, and would serve as a useful alternative to the conventional methods of the eye irritation study. PMID- 8207762 TI - Interrelations of cadmium contents and histopathological changes in kidneys following single intravenous injection of cadmium-saturated metallothionein II in rats. AB - An interrelation of Cd-contents with hepato- and nephrotoxicities, and a mechanism for Cd-exclusion from kidneys were investigated in rats that received a single intravenous injection of either CdCl2 or Cd-saturated metallothionein II (Cd-MT-II) with doses of 0.1 and 0.3 mg Cd/kg body weight (b.w.). Between the livers and kidneys, higher uptake of Cd was observed in the liver in terms of CdCl2, and in the kidney in terms of Cd-MT-II. The CdCl2 at the two doses hardly showed any histopathological alterations in the livers and kidneys. The 0.1 mg Cd/kg b.w. of Cd-MT-II showed a slight injury in the kidneys, while hardly in the livers. At Day 1 of the 0.3 mg Cd/kg b.w. of Cd-MT-II, the renal Cd-contents reached the maximal value of 8.22 +/- 0.36 microgram/g wet tissue, and degeneration including necrosis and defluxion of proximal tubular cells were most highly observed. At Day 5 of the 0.3 mg Cd/kg b.w., the renal Cd-contents were lowered to 2.40 +/- 0.24 micrograms/g wet tissue, and fibrosis and regeneration of the proximal tubular cells were remarkably found. These findings strongly suggested that, in the case of administration of Cd-MT-II, the Cd taken into the kidneys was eliminated from there mainly by cellular death of the proximal tubulus and by their resultant defluxion. PMID- 8207763 TI - The effects of itraconazole on the immune responses in ICR mice. AB - Effects of itraconazole (ICZ) on the immune responses were studied in ICR mice. Mice were divided into 5 groups (10 mice/group), and ICZ at doses of 10, 20, 40 and 80 mg/kg were orally administered to mice once a day for 21 days. Mice were immunized and challenged with sheep red blood cells (SRBC). The body weight gains and the relative weights of spleen and thymus were dose-dependently increased following ICZ treatment. However, Plaque forming cells (PFC) and hemagglutination (HA) titers to SRBC were significantly suppressed in mice doses at 80 mg/kg ICZ, as compared with those in controls. Delayed-type hypersensitivity (DTH) reaction to SRBC, phagocyte activity and circulating leukocytes also were significantly decreased in mice dosed at 40 and 80 mg/kg ICZ. These studies demonstrate that ICZ treatment results in a marked suppression in both humoral and cell-mediated immune responses to SRBC at concentrations producing embryotoxicity. PMID- 8207764 TI - Prevalence of familial systemic lupus erythematosus in Taiwan. AB - A survey of familial occurrence of systemic lupus erythematosus (SLE) was conducted among 728 first-degree relatives of 102 SLE patients. All of the patients were from the rheumatology ward or outpatient clinic of Kaohsiung Medical College. Ten familial members (9.80%) in the 102 patients with SLE suffered from the same disease. Among them, one (20%) was from the 5 male patient families and 9 (9.28%) were from the 97 female patient families. The overall prevalence of SLE in first-degree relatives of SLE patients was 1.37% (10/728). PMID- 8207765 TI - [Lysosomal enzyme activity of cultured fetal cells in Chinese and its clinical application]. AB - Lysosomal storage diseases (LSD) are caused by deficient activity of specific lysosomal enzymes. Early diagnosis and selective termination is still the trend of therapy. The purpose of this study was to establish an assay system and investigate the reference range of lysosomal enzyme activity of cultured fetal cells in the Chinese population. Seventy amniotic fluid and 9 chorionic villi samples were collected and cultured in this study. Enzyme activity assay was done by synthesized 4-Mu-binded substrates. The activity was expressed as nmol/mg protein/hour. In cultured amniotic cells, the results showed 14-138 of alpha glucosidase, 8-133 of alpha-galactosidase, 32-470 of alpha-mannosidase, 101-1121 of alpha-fucosidase, 106-1321 of beta-galactosidase, 15-268 of beta-glucosidase, 11-279 of beta-glucuronidase, 101-1193 of Hexosaminidase A, and 886-6204 of N acetyl-alpha-glucosaminidase. In cultured chorionic villi samples, it showed 22 335 of alpha-glucosidase, 31-230 of alpha-galactosidase, 47-250 of alpha mannosidase, 35-218 of alpha-fucosidase, 49-934 of beta-galactosidase, 34-329, of beta-glucosidase, 57-379 of beta-glucuronidase, and 328-3412 of Hexosaminidase A. The enzyme activity was not correlated with the gestation age when sample was obtained. Furthermore, there was no statistical significance among the range of amniotic cells, chorionic villi samples, skin fibroblasts and peripheral leukocytes for each enzyme studied. It is suggested that the synthesis of lysosomal enzymes has been mature since the early fetal state, and the samples obtained as early as 8 weeks of gestation age can be used for early diagnosis of lysosomal storage diseases. PMID- 8207766 TI - [Characterization of trimethoprim resistance in Shigella]. AB - Ninety-seven Shigella strains from 1982 to 1987 were isolated. When these isolates were tested with minimal inhibitory concentrations of trimethoprim, twenty-two were found to be resistant. Among these, 10 were found to be S. flexneri, and 12 to be S. sonnei. In addition, all of these 22 isolates were found to have multiple drug resistance. In order to determine the type of dihydrofolate reductase (DHFR) genes in these 22 trimethoprim-resistant isolates, colony hybridization with probes representing types I, II, III and V DHFR, were used. The results revealed the presence of type I DHFR gene in all of these isolates. Further southern hybridization indicated that the type I DHFR gene was located on plasmids. In order to determine whether a trimethoprim resistant gene existed as a functional transposable element in these isolates, we used a specific probe to detect the prevalence of Tn7. However, no positive hybridization was found. The relationship between the trimethoprim resistant gene and integron is characterized by the fact that the integrase gene, in our study, was frequently found in all of the 22 resistant isolates. These results indicate that trimethoprim resistant genes might transfer among bacteria via site-specific integration. PMID- 8207767 TI - [Workplace risk factors associated with eye syndrome in office workers]. AB - Four large sealed office buildings were investigated to determine the relationship between the prevalence of sick building syndrome and the indoor air quality. Questionnaires were distributed to all building occupants. Respondents suffered from upper airway, eye, lower airway and many less specific complaints. Multivariate logistic regression analyses were conducted to assess workplace risk factors associated with eye syndrome. Working with visual display terminals, glare, use of desk lamp, fabric-covered partitions, new carpet, too dim, too bright and lack of openable windows correlated significantly with the prevalence of eye syndrome. PMID- 8207768 TI - [MRI of postmortem brains]. AB - We studied 18 formalin-fixed brains using MRI, and correlated our data with subsequent gross and microscopic examinations. 9 of our patients died from brain diseases (stroke due to infarction 4, stroke due to hemorrhage 1, encephalitis 2, head injury 1, brain tumor 1). 9 of our patients died from non-CNS diseases (stomach cancer 1, colon cancer 1, liver cirrhosis 1, myocardial infarction 2, trauma 4). In MRI of postmortem brain, T1WI and T 2WI was able to clearly show the myelination process of brainstem, basal ganglia, internal capsule and optic radiation in a 2 months-old-boy. The findings were similar to MRI of live infants. In normal adult postmortem brains, the T1WI showed a relatively low signal intensity of white matter as compared to gray matter. The pictures were similar to proton density images, not T1WI of normal adult brains. The reason why the signal intensity of the white matter was lower than the gray matter may have been due to lysis of lipid of myelin sheath in the formalin solution. Postmortem MRI was able to detect the periventricular hyperintensity (corresponding to arteriosclerotic encephalopathy) and subcortical hyperintensity spots (which corresponding to the widening of the Virchow-Robin perivascular space because of arteriosclerosis) in the brains of our elderly patients. Postmortem MRI detected the intracerebral hemorrhage, which appeared as a dark signal in both short and long TR images. However, MRI did not show blood in the ventricles, sulci, or superficial hemorrhages in the cortex of brain. Brain edema was revealed in the postmortem MRI and appeared as low signal intensity in T1WI and hyperintensity in T2WI. It was associated with a significant mass effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207769 TI - Leiomyosarcoma, leiomyomatosis in von Recklinghausen's disease: report of case. AB - A 48-year-old female patient with von Recklinghausen's disease was admitted to Kaohsiung Medical College Hospital due to massive hematochezia. The emergent mesentery arteriography revealed multiple hypervascular small intestinal lesions but no contrast extravasation. The endoscopic examination revealed a blood-filled small intestine with normal colonic mucosa. Laparotomy was carried out and multiple extraluminal masses on antimesenteric side of the small intestine were found. Segmental resection of the small intestine resulted in resolution of her symptom. The largest mass was diagnosed as leiomyosarcoma, and the others were diagnosed as leiomyoma. Histologically, differential diagnosis between leiomyosarcoma and leiomyoma is not clear cut, because it is based on a number of differentiating features. Surgical resection is the treatment of choice for intestinal leiomyosarcoma. The long-term follow-up of this patient is mandatory. PMID- 8207770 TI - Holoprosencephaly and trisomy 13 in a fetus with maternal early gestational amphetamine abuse--a case report. AB - We report a congenital anomalous fetus with holoprosencephaly, prenatally diagnosed by sonography and MR scan at the twenty-sixth week during the gestational period. Chromosome analysis by amniocentesis revealed trisomy 13 (47,XY,+13). The diagnosis was confirmed by autopsy. After induction, external examination showed a proboscis-like nose on the normal nose position. The right foot showed polydactylia with wide separation of the fifth and sixth toes. We found that the mother was an abuser of amphetamine at an early gestational age. The teratogenic effect of D-amphetamine on animals has been noted, but no previous clinical case of a congenital anomalous fetus and maternal abuse of amphetamine has been reported. This case report is the first to reveal holoprosencephaly and trisomy 13, with maternal early gestational abuse of amphetamine. PMID- 8207771 TI - Synthetic and cytotoxic studies of alpha-methylene-gamma-butyrolactone bearing pyrimidines. AB - A total of ten pyrimidine alpha-methylene-gamma-butyrolactones were synthesized as potential antitumor agents on the basis of their possible action as Michael acceptors for DNA/RNA and cellular enzymes. The synthesis of these heterocycles involved a convenient Reformatsky-type reaction of pyrimidinyl ketones with ethyl alpha-(bromomethyl)acrylate. The preliminary in vitro cytotoxic assay indicated that these synthetic compounds were essentially active against the growth of KB, Hep-2, HeLa and Colo-205 cells. Among them, 5'-biphenyl-5'-(uracil-1-ylmethyl)-2' oxo-3'-methylenetetrahydr ofuran (5f) demonstrated to be the most potent antileukemic agent. PMID- 8207772 TI - Acute thoracic aortic occlusion resulting from complex aortic dissection and presenting as paraplegia. AB - Acute paraplegia from an aortic occlusion or dissection is a surgical emergency. Prompt recognition and treatment may mitigate irreversible spinal cord injury. Aortography is commonly used when an aortic lesion is suspected as the cause of acute paraplegia. Transesophageal echocardiography is becoming increasingly used for the evaluation of aorta, diagnosing aortic dissection promptly at the bedside, and was able to define the cause of the spinal cord ischemia. PMID- 8207773 TI - MR angiographic diagnosis of recanalization in a thrombosed pulmonary arteriovenous malformation. AB - Pulmonary arteriovenous malformation (PAVM) results from an anomalous communication between a pulmonary artery and vein and may lead to life threatening hemoptysis. Pulmonary angiography is the standard diagnostic technique but may be falsely negative in the unusual instance of a thrombosed PAVM. We report a patient with a thrombosed PAVM in which the initial pulmonary angiogram incorrectly suggested pulmonary embolism. A subsequent magnetic resonance (MR) angiogram demonstrated recanalization of the PAVM, thus establishing the true nature of the lesion and leading to appropriate intervention. PMID- 8207774 TI - Appropriate window and level settings in CT-guided biopsies. AB - The purpose of this study was to investigate the factors that help determine the needle tip location during computed tomographic (CT)-guided thin needle aspirations. We devised a model using a bottle filled with air, mineral oil, and water into which we could insert a needle. We then obtained CT images using both 5- and 10-mm slice thicknesses and determined the Hounsfield units (HUs) in regions of interest surrounding the needle shaft and some distance away from the needle shaft. We demonstrated that the presence of the needle increases the average HUs of the background both in the same region of interest and in the region of interest some distance from the needle. This effect is seen in air, fat, and water and thus occurs regardless of the attenuation of the background medium. A decrease in slice thickness causes this effect to be even more marked. These experimental results coincided with the theoretical results obtained from an equation that approximates the HUs of the pixels. PMID- 8207775 TI - Improved method of preparation of inflated-fixed lung for radiologic-pathologic correlation. AB - The technique of inflation and fixation of the lung with polyethylene glycol is useful for specimen radiography and radiologic-pathologic correlation, but it is limited by poor histologic staining of the fixed tissue. To improve staining we used formalin to distend and fix the lung before standard fixation with a polyethylene glycol mixture. In this preliminary study, canine and infant lungs, and lungs from three cases of lung cancer were examined. The modified technique provided high-quality staining and satisfactory specimen radiography in all cases except one of the lung cancers; in this case excessive shrinkage occurred and degraded radiographic quality. We conclude that the new method of preparation permits both specimen radiography and high quality staining of the fixed tissue. PMID- 8207776 TI - Quantitative metabolic PET imaging of a plasma cell granuloma. AB - We report a patient who underwent surgical resection of two lung nodules that proved to be recurrent plasma cell granuloma, also known as inflammatory pseudotumor. Prior to surgery, positron emission tomography (PET) was performed with 18F-labeled fluoro-2-deoxy-D-glucose (18FDG) and rubidium-82 (82Rb). The 18FDG PET scan revealed that the nodules corresponded to two areas of intense uptake. PET imaging with 82Rb, the marker of flow, also showed intense uptake. Thus, PET demonstrated both a high degree of metabolic activity and increased perfusion. These features suggest a lesion with high cellular activity rather than a simple reparative process. The true nature of this lesion remains unknown. PMID- 8207777 TI - Mediastinal perigraft seroma: CT and MR imaging. AB - We report a patient who developed a perigraft seroma after a modified Blalock Taussig procedure in which a polytetrafluoroethylene (Gore-tex) graft was used. Computed tomography and magnetic resonance were instrumental in the evaluation of this seroma. PMID- 8207778 TI - Paratracheal radiolucency as a sign of tracheal disruption after heart-lung transplantation. AB - Focal mediastinal radiolucency to the immediate left of the distal part of the trachea was evident on a frontal chest radiograph 12 days after heart-lung transplantation in a 31-year-old woman. Bronchoscopy revealed ulcerating necrosis immediately distal to the tracheal anastomosis. We conclude that chest radiography may show focal mediastinal air as the first sign of anastomotic necrosis of a major airway after lung transplantation. PMID- 8207779 TI - Interstitial thickening in pulmonary alveolar microlithiasis: an underappreciated finding. AB - We report a case of pulmonary alveolar microlithiasis in which interstitial thickening is a prominent radiographic feature. We wish to emphasize this finding. PMID- 8207780 TI - Pulmonary drug toxicity following high-dose chemotherapy with autologous bone marrow transplantation: CT findings in 20 cases. AB - We retrospectively evaluated the computed tomography (CT) findings in 20 patients with pulmonary drug toxicity that followed high-dose chemotherapy and autologous bone marrow transplantation (ABMT). Eighty-five patients with Stage II or III breast cancer that involved > or = 10 axillary lymph nodes were enrolled in a treatment protocol that included four cycles of standard-dose therapy (CAF) followed by one cycle of high-dose treatment (CPA/cDDP/BCNU). After chemotherapy, ABMT was performed. Twenty-six patients (31%) developed pulmonary drug toxicity. Serial thoracic CT studies were available in 20 of these 26 patients. All 20 patients exhibited clinical symptoms (i.e., dyspnea, nonproductive cough, and fever) and abnormal pulmonary function following transplantation. Thirteen patients had pathologically proven drug toxicity, and seven patients had clinical features and treatment responses highly suggestive of this diagnosis. Multiple sputum and blood cultures were negative in all patients. CT scans of 13 patients (65%) demonstrated scattered, predominantly peripheral ground-glass or consolidated opacities that occasionally looked nodular or masslike. Two patients (10%) had CT scans suggestive of pulmonary edema and in five patients (25%), the CT examinations revealed no significant abnormalities. Pleural effusions and adenopathy were uncommon. Pulmonary drug toxicity after high-dose chemotherapy and ABMT should be suspected in the appropriate clinical and radiographic setting, and therapy may be initiated on the basis of these observations. PMID- 8207781 TI - Melanoma metastatic to the bronchus: radiologic features in two patients. AB - Two patients with cutaneous melanoma metastatic to the bronchus are described. Chest radiographs revealed only indirect signs of bronchial obstruction. Computed tomography (CT) clearly demonstrated the intraluminal lesion. Magnetic resonance (MR) imaging signal characteristics were not specific for melanoma. PMID- 8207782 TI - Miliary nodules, Hodgkin's disease, and eosinophilic granuloma. AB - We describe a patient with Hodgkin's disease (HD) who subsequently developed miliary lung nodules proven to be eosinophilic granuloma (EG). The differential diagnosis and a brief review of the pertinent literature is presented. PMID- 8207783 TI - Evolution of chest radiographs in treated patients with pulmonary tuberculosis and HIV infection. AB - A large number of patients with coexisting tuberculosis and HIV infection has been reported. The chest radiographic findings are well described and primarily consist of bilateral, medium-to-coarse reticulonodular opacities often associated with hilar and mediastinal adenopathy. The evolution of chest radiographic abnormalities following treatment for tuberculosis in patients with HIV infection has not been previously studied. Initial and follow-up chest films of 33 patients with tuberculosis and HIV infection were evaluated. All 25 patients whose only pulmonary infection was tuberculosis exhibited radiographic improvement after appropriate treatment. In 8 patients, the chest radiograph worsened while on tuberculosis therapy. In each of these individuals, a newly acquired nontuberculous pulmonary disease was diagnosed as the cause of radiographic deterioration. We conclude that chest radiographs in patients with tuberculosis and HIV-infection will improve with appropriate tuberculosis therapy. Worsening of the chest radiograph does not suggest a poor therapeutic response, but instead indicates the presence of another pulmonary disease. PMID- 8207784 TI - Pulmonary manifestations of cryptococcosis in patients with AIDS: CT features. AB - The computed tomographic (CT) scans and chest radiographs of 10 patients with AIDS and proven pulmonary cryptococcal infections were reviewed. In seven patients (70%), CT demonstrated pulmonary opacities that ranged in appearance from a perihilar interstitial pattern to an area of dense alveolar consolidation. Corresponding chest radiographs were less accurate in detecting interstitial opacities (2 of 5 patients, 40%) than the alveolar opacities (4 of 5 patients, 80%). Pulmonary nodules were identified in three patients (30%) by CT but were identifiable on the chest radiograph in only one patient (10%). The chest radiograph suggested hilar adenopathy in three patients although CT confirmed hilar adenopathy in only one patient. In one patient, a small pleural effusion, not appreciated on the chest radiograph, was detected by CT. CT may add additional information in the diagnosis of pulmonary Cryptococcus neoformans. PMID- 8207785 TI - Left ventricular-coronary sinus fistula after mitral valve replacement: case report and ultrafast CT findings. AB - Postoperative fistula from left ventricle to right atrium is a rare complication of mitral valve surgery. We describe a case identified by ultrafast computed tomography (CT) and we review the literature regarding this entity. PMID- 8207786 TI - Magnetic resonance imaging of pseudocoarctation of the aorta: a case report. AB - We present a case of pseudocoarctation of the aorta with associated left subclavian artery dilatation that was diagnosed by magnetic resonance (MR) imaging and confirmed by angiography. This case demonstrates the advantages of MR imaging over other modalities for diagnosing this disorder. PMID- 8207787 TI - Chronic traumatic pseudoaneurysm of the thoracic aorta: a report of two cases following gunshot injury. AB - Gunshot injury to the thoracic aorta is nearly always fatal. Although the victim usually will succumb to exsanguination or tamponade in the minutes following injury, unusual cases of occult injury occur when a pseudoaneurysm, occlusion, or fistula forms at the site of injury. We report two patients with gunshot injury to the thoracic aorta that resulted in chronic pseudoaneurysms that went undetected for 325 and 46 days, respectively. Computed tomography and aortography were utilized to verify these pseudoaneurysms, and both patients underwent successful surgical repair. PMID- 8207788 TI - Vertebral vein migration of a long-term central venous access catheter: a cause of brachial plexopathy. AB - We report a patient whose central venous catheter tip had migrated into the vertebral vein. Infusion of chemotherapy agents for cancer through this catheter resulted in brachial plexopathy. PMID- 8207789 TI - Stable expression of the vaccinia virus K1L gene in rabbit cells complements the host range defect of a vaccinia virus mutant. AB - Modified vaccinia virus Ankara (MVA), having acquired genomic deletions during passage in chicken embryo fibroblasts, is highly attenuated and unable to productively infect most mammalian cell lines. Multiplication in rabbit kidney derived RK13 cells, but not other nonpermissive cells, can be restored by insertion of the vaccinia virus K1L gene into the MVA genome. During nonproductive infection of RK13 cells by MVA, transcription of representative viral early genes was revealed by Northern (RNA) blotting, whereas synthesis of an intermediate mRNA and replication of viral DNA could not be detected. Despite the persistence of viral early mRNA for at least several hours, synthesis of virus-induced polypeptides occurred only during the first hour and was followed by abrupt inhibition of all protein synthesis. Transfection of RK13 cells with a eukaryotic expression plasmid that contained the K1L gene allowed MVA infection to proceed to late stages of viral protein synthesis. Moreover, RK13 cell lines that stably expressed the K1L gene were permissive for MVA as well as a K1E deletion mutant of the WR strain of vaccinia virus. This is the first description of the complementation of a poxvirus mutant by cells that stably express a viral gene. PMID- 8207790 TI - Identification of binding sites for the 86-kilodalton IE2 protein of human cytomegalovirus within an IE2-responsive viral early promoter. AB - The 86-kDa IE2 protein (IE86) of human cytomegalovirus (HCMV) can act as both an activator and a repressor of gene expression. The mechanisms for both of these functions are not well defined. It has recently been demonstrated that this protein has sequence-specific DNA binding properties: it interacts directly with a target sequence that is located between the TATA box and the cap site of its own promoter. This sequence, termed the CRS (cis repression signal) element, is required for negative autoregulation of the IE1/IE2 enhancer/promoter by IE2. We demonstrate now that binding of this protein to DNA is not confined to this site but occurs also within an early promoter of HCMV that has previously been shown to be strongly IE2 responsive. By DNase I protection analysis using a purified, procaryotically expressed IE2 protein, we could identify three binding sites within the region of -290 to -120 of the UL112 promoter of HCMV. Competition in DNase I protection experiments as well as gel retardation experiments showed that the identified binding sites are specific and have high affinity. Deletion of IE2 binding sites from this promoter reduced the level of transactivation; however, the remaining promoter could still be stimulated about 40-fold. Constructs in which IE2 binding sites were fused directly to the TATA box of the UL112 promoter did not reveal a significant contribution of these sequences to transactivation. However, if an IE2 binding site was reinserted upstream of nucleotide -117 of the UL112 promoter, an increase in transactivation by IE2 was obvious, whereas a mutated sequence could not mediate this effect. This finding suggests that DNA bound IE2 can contribute to transactivation but seems to require the presence of additional transcription factors. Moreover, a comparison of the detected IE2 binding sites could not detect a strong homology, suggesting that this protein may be able to interact with a broad spectrum of different target sequences. PMID- 8207791 TI - Alphaherpesvirus origin-binding protein homolog encoded by human herpesvirus 6B, a betaherpesvirus, binds to nucleotide sequences that are similar to ori regions of alphaherpesviruses. AB - We previously identified a human herpesvirus 6B (HHV-6B) homolog of the alphaherpesvirus origin-binding protein (OBP), exemplified by the herpes simplex virus type 1 UL9 gene product. This finding is of particular interest because HHV 6B is otherwise more closely related to members of the betaherpesvirus subfamily. The prototypic betaherpesvirus, human cytomegalovirus, does not encode an obvious OBP homolog and contains a more complex origin of replication than do alphaherpesviruses. Thus, analysis of the function of the HHV-6B OBP homolog is essential for understanding the mechanism of HHV-6B DNA replication initiation. The HHV-6B OBP homolog, OBPH6B, was expressed in vitro by coupled transcription and translation and in insect cells by infection with recombinant baculoviruses. The expressed protein bound to two DNA sequences located upstream of the HHV-6B major DNA-binding protein gene homolog, within a region that was predicted to serve as an origin of replication on the basis of its sequence properties. The binding sites lie within 23-bp segments and are similar to OBP-binding sites of herpes simplex virus type 1. The two OBPH6B-binding sequences are separated by an AT-rich region and have an imperfect dyad symmetry as do the alphaherpesvirus origin regions. We identified OBPH6B transcripts by reverse transcription PCR in HHV-6B-infected Molt-3 cells. These results suggest that OBPH6B functions in a manner analogous to the alphaherpesvirus OBP and that initiation of HHV-6B DNA replication may resemble that of alphaherpesviruses. PMID- 8207792 TI - Identification of sequence elements in the human cytomegalovirus DNA polymerase gene promoter required for activation by viral gene products. AB - To determine the mechanisms involved in the regulation of human cytomegalovirus early gene expression, we have examined the gene that encodes the viral DNA polymerase (UL54, pol). Our previous studies demonstrated that sequences required for activation of the pol promoter by immediate-early proteins are contained within a region from -128 to +20 and that cellular proteins can bind to this activation domain. In this study, we demonstrate by competition analysis that binding of cellular proteins to pol is associated with an 18-bp region containing a single copy of a novel inverted repeat, IR1. Time course analysis indicated that viral infection increased the level of protein binding to IR1, concurrent with the activation of the pol promoter. Mutation of the IR1 element abrogated binding of cellular factors to the pol promoter and reduced by threefold the activation by immediate-early proteins. Similarly, mutation of IR1 rendered the promoter poorly responsive to activation by viral infection. Mutation of additional sequence elements in the pol promoter had little effect, indicating that IR1 plays the major role in pol promoter regulation. These studies demonstrate that the interaction between cellular factors and IR1 is important for the regulation of expression of the polymerase gene by viral proteins. PMID- 8207793 TI - Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells. AB - Dysregulation of cytokines secreted by T cells may play an important role in the pathogenesis of AIDS. To investigate the effects of human immunodeficiency virus type 1 (HIV-1) Tat on interleukin-2 (IL-2) expression, we used IL-2 promoter chloramphenicol acetyltransferase constructs and IL-2-secreting Jurkat T cells as a model system. Transient expression of HIV-1 Tat induced a five- to eightfold increase in IL-2 promoter activity in Jurkat T cells stimulated with phytohemagglutinin and phorbol myristate acetate. IL-2 secretion was increased more than twofold in both Jurkat T cells and primary T cells stimulated by extracellular HIV-1 Tat protein. Analysis of mRNA suggested that Tat exerts its effect on IL-2 primarily at the transcriptional level. The NF-kappa B site at positions -206 to -195 of the IL-2 promoter was required but not sufficient for the Tat effect. The Tat-mediated increase in IL-2 promoter activity could selectively be blocked by antisense tat or-unlike the analogous effect of human T cell lymphotropic virus type 1 Tax-by cyclosporin A. The observed increase in IL 2 levels might facilitate virus spread from or to T cells. Furthermore, it might contribute to the hypergammaglobulinemia or, together with other cytokines found to be dysregulated, the T-helper cell dysfunctions observed in AIDS patients. PMID- 8207794 TI - A poxvirus protein with a RING finger motif binds zinc and localizes in virus factories. AB - Shope fibroma virus (SFV) is a Leporipoxvirus closely related to the highly virulent myxoma virus. The DNA sequence of the BamHI N fragment of the SFV DNA genome was determined, and the single complete open reading frame (N1R) was characterized. The protein encoded by the N1R gene was found to contain a C3HC4 RING finger motif at the C terminus. This C3HC4 motif is the hallmark of a growing family of proteins, many of which are involved in regulation of gene expression, DNA repair, or DNA recombination. Complete homologs of the SFV N1R gene were also detected in variola virus, myxoma virus, and vaccinia virus strain IHD-W. In contrast, the gene is completely absent from vaccinia virus strain Copenhagen, and in vaccinia virus strain WR, the open reading frame is truncated prior to the zinc binding domain because of an 11-bp deletion, thus producing a frameshift and premature stop codon. Recombinant N1R protein from SFV was expressed in Escherichia coli and shown to bind zinc in a specific manner. Using fluorescence microscopy to visualize a peptide epitope tag (derived from ICP27 of herpes simplex virus) fused to the N terminus of the poxvirus proteins, we observed that the N1R protein of SFV and its homologs in myxoma virus and vaccinia virus IHD-W were localized primarily to the virus factories in the cytoplasm of infected cells and, to a lesser degree, the host cell nucleus. The truncated protein of vaccinia virus strain WR failed to localize in this manner but instead was observed throughout the cytoplasm. PMID- 8207795 TI - Unusual phosphorylation sequence in the gpIV (gI) component of the varicella zoster virus gpI-gpIV glycoprotein complex (VZV gE-gI complex). AB - Varicella-zoster virus (VZV) glycoprotein gpIV, to be renamed VZV gI, forms a heterodimer with glycoprotein gpI (gE) which functions as an Fc receptor in virus infected cells. Like VZV gpI (gE), this viral glycoprotein is phosphorylated in cell culture during biosynthesis. In this report, we investigated the nature and specificity of the phosphorylation event involving VZV gpIV (gI). Phosphoamino acid analysis indicated that gpIV (gI) was modified mainly on serine residues. To identify the precise location of the phosphorylation site on the 64-kDa protein, a step-by-step mutagenesis procedures was followed. Initially a tailless mutant was generated, and this truncated product was no longer phosphorylated. Thereafter, point mutations were made within the cytoplasmic tail of gpIV (gI) at potential phosphorylation sites. The phosphorylation site was localized to the following sequence: Ser-Pro-Pro (amino acids 343 to 345). Examination of the point mutants established that serine 343 in the cytoplasmic tail was the major phosphoacceptor. In addition, we found that the prolines located immediately to the C terminus of serine 343 were an integral part of the kinase recognition sequence. This site was located immediately N terminal to a predicted beta-turn secondary structure. By comparison with known substrate consensus sequences for various protein kinases, these data suggested that the phosphorylation of VZV gpIV (gI) was catalyzed by a proline-directed protein kinase. Computer homology analysis of other alphaherpesviruses demonstrated that a similar potential phosphorylation site was highly conserved in the cytoplasmic tails of herpes simplex virus type 1 gI, equine herpesvirus type 1 gI, and pseudorabies virus gp63. PMID- 8207796 TI - Interacting domains of E2F1, DP1, and the adenovirus E4 protein. AB - Recent experiments demonstrate that a family of related proteins constitute the E2F transcription factor activity and that the interaction of two of these gene products, E2F1 and DP1, generates a heterodimer with DNA binding and transcriptional activating capacity. Previous experiments have shown that the adenovirus E4 19-kDa protein facilitates the formation of a stable E2F dimer on the adenovirus E2 promoter. We now show that coexpression of the E2F1 and DP1 products in transfected SAOS-2 cells, together with the E4 product, generates a multicomponent complex with specificity to the adenovirus E2 promoter. Using a yeast two-hybrid assay system, we find that the E2F1 hydrophobic heptad repeat (E2F1 amino acid residues 206 to 283) allows interaction with a corresponding domain of the DP1 protein (amino acids 196 to 245). We also find that the adenovirus E4 protein interacts with the DP1 hydrophobic heptad repeat domain, but we could not detect a direct interaction between E2F1 and E4. Additional assays demonstrate that the E4 protein can dimerize. Since our previous experiments have shown that mutations within the E2F1 hydrophobic heptad repeat element abolish the E4-mediated transcription enhancement in transfection assays, we conclude that the E4 protein likely interacts with the E2F1-DP1 heterodimer by directly binding to the DP1 product. As a consequence of the ability of E4 to dimerize, we propose that the stable complex formed on the two E2F sites within the E2 promoter is composed of two E2F1-DP1 heterodimers held together by an E4 dimer. PMID- 8207797 TI - Regulation of int gene expression in bacteriophage P2. AB - The int gene of bacteriophage P2 is the only viral gene necessary for the integration of P2 into the Escherichia coli host chromosome. This gene is situated between the phage attachment site, attP, and the repressor C gene, and is cotranscribed with C from the Pc promoter, towards attP. The Pc promoter is negatively controlled by the cox gene, which is the first gene of the early operon. In vitro recombination assays have indicated that in P2 an overproduction of Int is deleterious to the integrative process. We report here that the level of int expression is affected by several different mechanisms after transcriptional initiation. First, a partial transcription termination signal located between the int and C genes reduces the the transcriptional readthrough by about 30%. Second, the ribosome binding site and AUG codon of the int gene are located in a putative stem-loop structure, which may inhibit the initiation of translation. The nip1 mutation (a G to A substitution at the 22nd coding nucleotide of int which results in an increased efficiency of excision) is shown to relieve this inhibition, possible through the formation of an alternative mRNA secondary structure. However, the third and probably most important control of int expression in P2 seems to be that of posttranscriptional autoregulation. The binding site of the Int protein on int gene mRNA is shown to extend into the ribosome binding site of int, supporting our earlier proposed model of competitive binding between Int and ribosomes. PMID- 8207798 TI - Simian virus 40 large T antigen host range domain functions in virion assembly. AB - The simian virus 40 (SV40) T antigen host range mutants dl1066 and dl1140 display a postreplicative block to plaque formation which suggests a novel role for T antigen late in the viral life cycle. The host range mutants dl1066 and dl1140 are able to grow in and plaque on BSC but not on CV1 monkey kidney cells, a normally permissive host. Previous work showed that in CV1 cells infected with dl1066 and dl1140, levels of viral DNA replication and of late capsid protein accumulation were only slightly reduced and the failure to accumulate agnoprotein was not likely to be the major factor responsible for the mutants' growth defect. Here we show that the host range mutants are defective in the assembly of viral particles. SV40 assembly proceeds as the progressive conversion of 75S viral chromatin complexes to 200S-240S assembled virions. When virus-infected cell extracts are separated on 5 to 40% sucrose gradients, wild-type extracts show the greatest accumulation of viral late protein in the 200S-240S fractions corresponding to the assembled virus peak and lesser amounts in the 75S-150S fractions corresponding to immature assembly intermediates. The host range mutants dl1066 and dl1140 grown in nonpermissive CV1 cells, however, failed to assemble any appreciable amounts of mature 200S-240S virions and accumulate 75S intermediates, whereas in permissive BSC cells, levels of assembly were more slightly reduced than those of the wild type. Analysis of the protein composition of gradient fractions suggests that SV40 assembly proceeds by a mechanism similar to that proposed for polyomavirus and suggests that the host range blockage may result from a failure of such mutants to add VP1 to 75S assembly intermediates. PMID- 8207799 TI - Characterization of replication-competent retroviruses from nonhuman primates with virus-induced T-cell lymphomas and observations regarding the mechanism of oncogenesis. AB - Rapidly progressive T-cell lymphomas were observed in 3 of 10 rhesus monkeys several months after autologous transplantation of enriched bone marrow stem cells that had been transduced with a retroviral vector preparation containing replication-competent virus (R. E. Donahue, S. W. Kessler, D. Bodice, K. McDonagh, C. Dunbar, S. Goodman, B. Agricola, E. Byrne, M. Raffeld, R. Moen, J. Bacher, K. M. Zsebo, and A. W. Nienhuis, J. Exp. Med. 176:1124-1135, 1992). The animals with lymphoma appeared to be tolerant to retroviral antigens in that their sera lacked antibodies reactive with viral proteins and contained 10(4) to 10(5) infectious virus particles per ml. By molecular cloning and DNA sequencing, we have now demonstrated that the serum from one of the monkeys contained a replication-competent retrovirus that arose by recombination between vector and packaging encoding sequences (vector/helper [V/H] recombinant) in the producer clone used for transduction of bone marrow stem cells. Southern blot analysis demonstrated 14 or 25 copies of this genome per cell where present in two animals. The genome of a second replication-competent virus was also recovered by molecular cloning; it arose by recombination involving the genome of the V/H recombinant and endogenous murine retroviral genomes in the producer clone. Twelve copies of this amphotropic virus/mink cell focus-forming virus genome were present in tumor DNA of one animal, but it was not found in tumor DNA of the other two animals with lymphoma. Southern blot analysis of DNA from various tissues demonstrated common insertion site bands in several samples of tumor DNA from one animal, suggesting clonal origin of the lymphoma. Our data are most consistent with a pathogenic mechanism in which chronic productive retroviral infection allowed insertional mutagenesis of critical growth control genes, leading to cell transformation and clonal tumor evolution. PMID- 8207800 TI - Transcriptional analysis of the region of the herpes simplex virus type 1 genome containing the UL8, UL9, and UL10 genes and identification of a novel delayed early gene product, OBPC. AB - The region of the UL component of the herpes simplex virus type 1 genome between nucleotides 17,793 and 25,150 includes three open reading frames that code for the protein products of the UL8, UL9, and UL10 genes (D.J. McGeogh, M.A. Dalrymple, A.J. Davison, A. Dolan, M.C. Frame, D. McNab, L.J. Perry, J.E. Scott, and P. Taylor, J. Gen. Virol. 69:1531-1574, 1988). We have mapped and characterized the overlapping transcripts in this region and have found that, in addition to the low-abundance UL8 and UL9 transcripts and the abundant UL10 transcript, at least two additional transcription units, designated UL8.5 and UL9.5, are specified by this region of the genome. The 5' ends of the UL8, UL8.5, and UL9 transcripts were mapped to nucleotides 20,682, 22,351, and 23,381, respectively. The 5' terminus of the UL9.5 transcript has not yet been mapped. The 3' ends of the UL8, UL8.5, UL9, and UL9.5 transcripts are coterminal at nucleotide 18,197. The 5' end of the UL10 mRNA, which is transcribed from the strand opposite that specifying the UL8, UL8.5, UL9, and UL9.5 transcripts, lies within the UL9 open reading frame at nucleotide 22,944, while the 3' terminus was mapped to nucleotide 24,666. Time course studies demonstrated that the UL8 and UL9 transcripts are members of the early kinetic class, the UL8.5 mRNA is a delayed-early transcript, and the UL9.5 and UL10 transcripts belong to the true late kinetic class. Examination of the nucleotide sequence of the UL8.5 transcript revealed a potential open reading frame that overlaps and is in frame with the C-terminal half of the open reading frame encoding the origin-binding protein (OBP), the product of the UL9 gene. In vitro translation of the UL8.5 transcript demonstrated that it encodes a protein with an apparent molecular mass of 53 kDa. This protein was recognized by antibody directed against the C terminal region of OBP and has thus been designated OBPC. A protein with an identical apparent molecular mass was also recognized by this antibody in infected-cell lysates, indicating that OBPC is synthesized during viral infection. PMID- 8207801 TI - Inhibition of p53 DNA binding by human papillomavirus E6 proteins. AB - Transformation by the human papillomavirus (HPV) early gene products, E6 and E7, involves their interaction with cellular proteins p53 and Rb. Using glutathione S transferase (GST) fusion proteins, we found that HPV E6 bound human p53 and that the relative efficiency of binding varied such that the GST-HPV type 16 E6 (16E6) protein bound p53 with highest affinity, followed by GST-31E6, GST-18E6, and GST 11E6. The GST-E6 fusion proteins were sufficient for binding p53 purified from a baculovirus expression system as well as in vitro translation sources, while no association was observed with GST-18E7 or a GST-16E6 mutant bearing a five-amino acid deletion in E6. When the site-specific DNA binding activity of p53 was examined in the presence of GST-E6 proteins, an inhibition of DNA binding was observed. The degree of inhibition correlated with the relative affinity of different E6 proteins for p53; thus, GST-16E6 was the most potent inhibitor of p53 DNA binding activity, and GST-11E6 was the least effective. Prevention of p53 DNA binding is likely to play a role in the abrogation of the transcriptional activity of p53 by HPV E6 and provides a further mechanism for E6 disruption of p53 growth suppressor function in addition to its role in directing specific degradation of p53 through the ubiquitin-mediated pathway. The variation in inhibition of DNA binding seen with the various E6 proteins may thus contribute to the differences in oncogenic potential seen among the HPV types. PMID- 8207802 TI - Complex functional interactions at the early enhancer of the PQ strain of BK virus. AB - BK virus is a human papovavirus that latently infects a majority of the world's population. There are more than 30 strains of the virus, most of which differ in the structure of the early enhancer region. The enhancer of the progenitor strain, WW, from which the other strains can be derived, consists of four conserved DNA domains, P, Q, R, and S. Rearrangement of the enhancer occurs upon passage in tissue culture and is thought to occur during virus replication. The strain under study, PQ, was selected upon passage of the Gardner strain (PPPQS) in the permissive cell line, Vero. Mutational analysis of the entire enhancer region demonstrates the importance of five cis-acting sequences: DNA sites B, C, and F, which have homology to the NF-1 protein binding sequence; one purine-rich motif designated A; and site D, which is similar to an SP-1 protein binding site. Two sites, B and C, appear to have a negative influence on gene activity. To study the functional interactions in more detail, promoter-enhancer constructions that contain different combinations of the five DNA sites linked to the chloramphenicol acetyltransferase gene were tested for early gene activity. The results reveal that the proteins binding to the enhancer functionally cooperate with each other. The effects of making mutations at the DNA sites are very similar to the effects of using excess enhancer DNA sequences to titrate the proteins that bind to the cis-acting DNA sites (in vivo competition). Moreover, the effects of changing the spacing between the DNA sites also demonstrate that there are cooperative interactions among the proteins that bind to the PQ strain enhancer. DNA sites B, C, and F are clearly protected from DNase I digestion by Vero cell nuclear proteins. In addition, mutation of each DNA site alters its sensitivity to DNase I in the presence of Vero cell proteins. Interestingly, mutation of site B affects protein binding to site B as well as to sites A, C, D, and F. These results suggest that cooperative functional and physical interactions occur at the early enhancer of the PQ strain. PMID- 8207803 TI - Epstein-Barr virus nuclear protein 2A forms oligomers in vitro and in vivo through a region required for B-cell transformation. AB - Epstein-Barr virus nuclear antigen 2 (EBNA-2) has been shown to be indispensable for immortalization of latently infected B lymphocytes, and it has been shown that EBNA-2 exists in a high-molecular-weight complex in these cells. In order to study the components of this protein machinery, we have purified baculovirus expressed EBNA-2 from insect cells to greater than 95% homogeneity. We have shown by both gel filtration and sucrose gradient analysis that the purified material corresponds to a multimer containing eight EBNA-2 subunits. This multimeric complex is stable in 1.0 M NaCl, suggesting that the self-association is quite strong in vitro. By expressing portions of the EBNA-2 open reading frame to generate fusion proteins in yeast cells, we have used the two-hybrid system to demonstrate that this self-association occurs in vivo and is mediated at least in part by a domain of EBNA-2 encompassing amino acids 122 to 344. Mutational analysis of the self-association function suggests that two subdomains that flank amino acid 232 may each play a role in EBNA-2 protein-protein interaction. PMID- 8207804 TI - Subclonal components of consensus fitness in an RNA virus clone. AB - Most RNA virus populations exhibit extremely high mutation frequencies which generate complex, genetically heterogeneous populations referred to as quasi species. Previous work has shown that when a large spectrum of the quasi-species is transferred, natural selection operates, leading to elimination of noncompetitive (inferior) genomes and rapid gains in fitness. However, whenever the population is repeatedly reduced to a single virion, variable declines in fitness occur as predicted by the Muller's ratchet hypothesis. Here, we quantitated the fitness of 98 subclones isolated from an RNA virus clonal population. We found a normal distribution around a lower fitness, with the average subclone being less fit than the parental clonal population. This finding demonstrates the phenotypic diversity in RNA virus populations and shows that, as expected, a large fraction of mutations generated during virus replication is deleterious. This clarifies the operation of Muller's ratchet and illustrates why a large number of virions must be transferred for rapid fitness gains to occur. We also found that repeated genetic bottleneck passages can cause irregular stochastic declines in fitness, emphasizing again the phenotypic heterogeneity present in RNA virus populations. Finally, we found that following only 60 h of selection (15 passages in which virus yields were harvested after 4 h), RNA virus populations can undergo a 250% average increase in fitness, even on a host cell type to which they were already well adapted. This is a remarkable ability; in population biology, even a much lower fitness gain (e.g., 1 to 2%) can represent a highly significant reproductive advantage. We discuss the biological implications of these findings for the natural transmission and pathogenesis of RNA viruses. PMID- 8207806 TI - Retroviral integration: in vitro host site selection by avian integrase. AB - Viral integrase catalyzes the integration of the linear viral DNA genome into the chromatin of the infected host cell, an essential step in the life cycle of retroviruses. The reaction produces a characteristic small duplication of host sequences at the site of integration, implying that there is a close juxtaposition of the viral DNA ends during a concerted integration event. We have used an in vitro assay to measure the concerted integration of virus-like plasmid DNA into naked lambda DNA catalyzed by virion purified avian integrase. In contrast to in vivo avian integration, which has strong fidelity for a 6-bp duplication, purified avian integrase in the context of this assay produced a distribution of duplication sizes, with the 6-bp size dominating. The metal cofactor Mg2+ induced increased fidelity for the 6-bp duplication relative to that with Mn2+. The immediate sequence of the host site may also influence duplication size in that we found sites that sustained multiple independent integration events producing the same duplication size. Additionally, for each set of cloned integration sites (5, 6, and 7 bp), a unique but similar symmetrical pattern of G/C and A/T sequence biases was found. Using duplex oligonucleotides as target substrates, we tested the significance of the 6-bp G/C and A/T pattern for site selection. In the context of this assay, which is likely dominated by the integration of only one viral end, the 6-bp pattern was not preferred. Instead, integration was predominantly into the 3' ends of the oligonucleotides. The combined results of the lambda and oligonucleotide assays indicated that although host site selection has properties in common with recognition of the viral DNA termini, the nonrandom sequence preferences seen for host site selection were not identical to the sequence requirements for long terminal repeat recognition. PMID- 8207805 TI - The tumor suppressor protein p53 strongly alters human immunodeficiency virus type 1 replication. AB - The p53 tumor suppressor gene product, a sequence-specific DNA-binding protein, has been shown to act as a transcriptional activator and repressor both in vitro and in vivo. Consistent with its role in regulating transcription are recent observations that the N-terminal acidic domain of p53 binds directly to the TATA box-binding protein subunit of the general transcription factor, TF IID. It is now demonstrated that wild-type p53 (wt-p53) inhibits human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-directed chloramphenicol acetyltransferase activity in a cotransfection assay system. Importantly, this effect of wt-p53 on the HIV-1 LTR was also demonstrated by in vitro transcription assays. In addition, the Sp1 sites and the TATA box of the HIV-1 LTR are demonstrated to be the primary sites involved with p53-induced effects on this viral promoter. The upstream elements of the HIV-1 LTR, including the nuclear factor kappa B (NF-kappa B) binding sites, decrease the p53-induced inhibitory effects on viral transcription. In the presence of the HIV-1 TAR sequence and Tat protein, the HIV-1 LTR also becomes less sensitive to wt-p53-induced inhibition. By using a retroviral vector delivery system, mutant forms of p53 genes were expressed in two HIV-1 latently infected cell lines, ACH-2 and U1. In the ACH-2 cell line, which is now demonstrated to contain an endogenous mutant form of p53 (amino acid 248, Arg to Gln), additional mutant p53 proteins did not alter HIV-1 replication. In U1 cells, which completely lack endogenous p53, overexpression of mutant p53 led to an increase in HIV-1 replication. Thus, these data indicate a possible functional role for wt-p53 and mutant p53 proteins in the control of HIV 1 replication patterns and proviral latency. PMID- 8207807 TI - Priming of immature thymocytes to CD3-mediated apoptosis by infection with murine cytomegalovirus. AB - Cytomegalovirus (CMV) causes severe clinical manifestations in immunocompromised hosts; however, it remains unclear whether the virus itself is a cause of immunosuppression or whether it is involved as an opportunistic bystander pathogen. This study was performed to elucidate the effect of CMV infection on the host's immune system. The double-positive thymocytes of BALB/c mice inoculated with a sublethal dose of murine CMV (MCMV) were extensively depleted by a 10-micrograms amount of anti-CD3 monoclonal antibody, while such an amount was unable to induce any apparent elimination of thymocytes in noninfected mice. In immature thymocytes of infected hosts, a markedly high level of susceptibility to apoptosis induction was found on treatment with anti-CD3 monoclonal antibody. Analysis of the signal transduction pathway of such double-positive thymocytes demonstrated a profound elevation of the intracellular Ca2+ level after anti-CD3 stimulation, implying that this aberrant mobilization of Ca2+ plays a crucial role in the signaling pathway leading these cells to an extensive apoptosis. Examination of the thymus by PCR was able to detect a low copy number of MCMV DNAs in thymic stromal cells but none at all in thymocytes. Therefore, it is suggested that a mechanism which is not associated with virus replication within the cells exerts a critical effect on rendering the thymocytes highly apoptosis sensitive in hosts infected with MCMV. PMID- 8207808 TI - Identification and characterization of the ICP22 protein of equine herpesvirus 1. AB - The equine herpesvirus 1 (EHV-1) homolog of herpes simplex virus type 1 ICP22 is differently expressed from the fourth open reading frame of the inverted repeat (IR4) as a 1.4-kb early mRNA and a 1.7-kb late mRNA which are 3' coterminal (V. R. Holden, R. R. Yalamanchili, R. N. Harty, and D. J. O'Callaghan, J. Virol. 66:664-673, 1992). To extend the characterization of IR4 at the protein level, the synthesis and intracellular localization of the IR4 protein were investigated. Antiserum raised against either a synthetic peptide corresponding to amino acids 270 to 286 or against a TrpE-IR4 fusion protein (IR4 residues 13 to 150) was used to identify the IR4 protein. Western immunoblot analysis revealed that IR4 is expressed abundantly from an open reading frame composed of 293 codons as a family of proteins that migrate between 42 to 47 kDa. The intracellular localization of IR4 was examined by cell fractionation, indirect immunofluorescence, and laser-scanning confocal microscopy. These studies revealed that IR4 is localized predominantly in the nucleus and is dispersed uniformly throughout the nucleus. Interestingly, when IR4 is expressed transiently in COS-1 or LTK- cells, a punctate staining pattern within the nucleus is observed by indirect immunofluorescence. Cells transfected with an IR4 mutant construct that encodes a C-terminal truncated (19 amino acids) IR4 protein exhibited greatly reduced intranuclear accumulation of the IR4 protein, indicating that this domain possesses an important intranuclear localization signal. Western blot analysis of EHV-1 virion proteins revealed that IR4 proteins are structural components of the virions. Surprisingly, the 42-kDa species, which is the least abundant and the least modified form of the IR4 protein family in infected cell extracts, was the most abundant IR4 protein present in purified virions. PMID- 8207809 TI - Multiple functions of capsid protein phosphorylation in duck hepatitis B virus replication. AB - We have investigated the role of phosphorylation of the capsid protein of the avian hepadnavirus duck hepatitis B virus in viral replication. We found previously that three serines and one threonine in the C-terminal 24 amino acids of the capsid protein serve as phosphorylation sites and that the pattern of phosphorylation at these sites in intracellular viral capsids is complex. In this study, we present evidence that the phosphorylation state of three of these residues affects distinct steps in viral replication. By substituting these residues with alanine in order to mimic serine, or with aspartic acid in order to mimic phosphoserine, and assaying the effects of these substitutions on various steps in virus replication, we were able to make the following inferences. (i) The presence of phosphoserines at residues 245 and 259 stimulates DNA synthesis within viral nucleocapsids. (ii) The absence of phosphoserine at residue 257 and at residues 257 and 259 stimulates covalently closed circular DNA synthesis and virus production, respectively. (iii) The presence of phosphoserine at position 259 is required for initiation of infection. The results implied that both phosphorylated and nonphosphorylated capsid proteins were necessary for a nucleocapsid particle to carry out all its functions in virus replication, explaining why differential phosphorylation of the capsid protein occurs in hepadnaviruses. Whether these differentially phosphorylated proteins coexist on the same nucleocapsid, or whether the nucleocapsid acquires sequential functions through selective phosphorylation and dephosphorylation, is discussed. PMID- 8207810 TI - Epstein-Barr virus recombinant molecular genetic analysis of the LMP1 amino terminal cytoplasmic domain reveals a probable structural role, with no component essential for primary B-lymphocyte growth transformation. AB - Previous recombinant Epstein-Barr virus molecular genetic experiments with specifically mutated LMP1 genes indicate that LMP1 is essential for primary B lymphocyte growth transformation and that the amino-terminal cytoplasmic and first transmembrane domains are together an important mediator of transformation. EBV recombinants with specific deletions in the amino-terminal cytoplasmic domain have now been constructed and tested for the ability to growth transform primary B lymphocytes into lymphoblastoid cell lines. Surprisingly, deletion of DNA encoding EHDLER or GPPLSSS from the full LMP1 amino-terminal cytoplasmic domain (MEHDLERGPPGPRRPPRGPPLSSS) had no discernible effect on primary B-lymphocyte transformation. These two motifs distinguish the LMP1 amino-terminal cytoplasmic domain from other arginine-rich membrane proximal sequences that anchor hydrophobic transmembrane domains. Two deletions which included the ERGPPGPRRPPR motif adversely affected but did not prevent transformation. This arginine- and proline-rich sequence is probably important in anchoring the first transmembrane domain in the plasma membrane, since these mutated LMP1s had altered stability and cell membrane localization. The finding that overlapping deletions of the entire amino-terminal cytoplasmic domain do not ablate transformation is most consistent with a model postulating that the transmembrane and carboxyl-terminal cytoplasmic domains are the likely biochemical effectors of transformation. PMID- 8207811 TI - Excision of DNA fragments corresponding to the unit-length a sequence of herpes simplex virus type 1 and terminus variation predominate on one side of the excised fragment. AB - DNA fragments corresponding to the unit-length a sequence of herpes simplex virus type 1 (HSV-1) were identified in HSV-1 DNA preparations extracted by the method of Hirt. The DNA fragments were molecularly cloned, and nucleotide sequences were determined. Most termini of the fragments were at sites on DR1 corresponding to the termini of linear HSV-1 DNA generated by the cleavage-packaging system. In one-step growth experiments, DNA fragments of the unit-length a sequence appeared simultaneously with the termini of linear HSV-1 DNAs produced by cleavage of circular and concatemeric DNAs. Therefore, excision of the unit-length a sequence appeared closely related to the cleavage-packaging system. Termini of the excised DNA fragments of the variant a sequence with two DR2 arrays varied on the L component side, while termini on the S-component side were at the site on DR1 corresponding to the authentic cleavage site. It is thus assumed that the cleavage-packaging system functions adequately on the DR1 second distal from the S component, and cleavages of other DR1 are rare and less accurate. If this notion is tenable, then most termini on the S-component side of the excised DNA fragments are derived from the second DR1 properly cleaved and should be constant, while termini on the L-component side are from regions on and around the DR1 third distal from the S component and may be variable. Cleavage of DR1 is likely to be affected by the topological relationship with the S component. PMID- 8207812 TI - The 5'-untranslated regions of picornavirus RNAs contain independent functional domains essential for RNA replication and translation. AB - The role of the 5'-untranslated region (5'UTR) in the replication of enteroviruses has been studied by using a series of poliovirus type 3 (PV3) replicons containing the chloramphenicol acetyltransferase reporter gene in which the 5'UTR was replaced by the 5'UTR of either coxsackievirus B4 or human rhinovirus 14 or composite 5'UTRs derived from sequences of PV3, human rhinovirus 14, coxsackievirus B4, or encephalomyocarditis virus. The results indicate that efficient replication of an enterovirus genome requires a compatible interaction between the 5'-terminal cloverleaf structure and the coding and/or 3'-noncoding regions of the genome. A crucial determinant of this interaction is the stem-loop formed by nucleotides 46 to 81 (stem-loop d). The independence of the cloverleaf structure formed by the 5'-terminal 88 nucleotides and the ribosome landing pad or internal ribosome entry site (IRES) was investigated by constructing a 5'UTR composed of the PV3 cloverleaf and the IRES from encephalomyocarditis virus. Chloramphenicol acetyltransferase gene-containing replicons and viruses containing this recombinant 5'UTR showed levels of replication similar to those of the corresponding genomes containing the complete PV3 5'UTR, indicating that the cloverleaf and the IRES may be regarded as functionally independent and nonoverlapping elements. PMID- 8207813 TI - Mutations in v-Src SH3 and catalytic domains that jointly confer temperature sensitive transformation with minimal temperature-dependent changes in cellular tyrosine phosphorylation. AB - We have analyzed two functionally significant amino acid alterations encoded by the temperature-sensitive (ts) v-src mutant of Rous sarcoma virus, LA32. The G-to V change at residue 300 in the catalytic domain nonconditionally impairs morphological transformation, in vitro kinase activity, in vivo tyrosine phosphorylation, and the cytoskeletal association of v-Src while rendering anchorage- and serum-independent growth ts. The R-to-P mutation in the SH3 domain subtly enhances morphological transformation but has no phenotype if the catalytic domain is inactivated. In the presence of the G-300-to-V mutation, this SH3 domain lesion does not affect v-Src in vitro kinase activity and cytoskeletal association, but it nonconditionally enhances cellular tyrosine phosphorylation and restores morphological transformation at the permissive temperature only. This ability to induce a ts transformed morphology, in concert with nonconditional elevations of cellular phosphotyrosine, suggest that a subset of v Src targets that are crucial to transformation may be affected in ts fashion by the SH3 mutation. Consistent with this, we find that the R-107-to-P mutation confers ts activity and tyrosine phosphorylation on the SH3-binding enzyme phosphatidylinositol 3'-kinase. Thus, both the SH3 and catalytic domain mutations in LA32 have some ts attributes and they cooperate in determining the mutant's behavior. The ts SH3 mutation is unique and offers the potential for deeper understanding of the function of this domain. PMID- 8207814 TI - Peptide immunogen mimicry of putative E1 glycoprotein-specific epitopes in hepatitis C virus. AB - Hepatitis C virus (HCV) accounts for most cases of acute and chronic non-A and non-B hepatitis with serious consequences that may lead to hepatocellular carcinoma. The putative envelope glycoproteins (E1 and E2) of HCV probably play a role in the pathophysiology of the virus. In order to map the immunodominant domains of the E1 glycoprotein, two epitopes from amino acid residues 210 to 223 (P1) and 315 to 327 (P2) were predicted from the HCV sequence. Immunization of mice with the synthetic peptides conjugated to bovine serum albumin induced an antibody response, and the antisera immunoprecipitated the E1 glycoprotein (approximately 33 kDa) of HCV expressed by recombinant vaccinia virus. A panel of HCV-infected human sera was also tested with the synthetic peptides by enzyme linked immunosorbent assay for epitope-specific responses. Of 38 infected serum samples, 35 (92.1%) demonstrated a spectrum of reactivity to the P2 peptide. On the other hand, only 17 of 38 (44.7%) serum samples were reactive to the P1 peptide. Strains of HCV exhibit a striking genomic diversity. The predicted P1 epitope showed localization in the sequence-variable region, and the P2 epitope localized in a highly conserved domain. Results from this study suggest that the E1 glycoprotein of HCV contains at least two potential antigenic epitopes. Synthetic peptides corresponding to these epitopes and antisera to these peptides may serve as the monospecific immunological reagents to further determine the role of E1 glycoprotein in HCV infection. PMID- 8207815 TI - Mutation in the UL97 open reading frame of human cytomegalovirus strains resistant to ganciclovir. AB - The same point mutation in the human cytomegalovirus UL97 open reading frame was found in three independently isolated ganciclovir-resistant mutants of strain AD169. Point mutations in the DNA polymerase genes of these strains have been previously identified (N.S. Lurain, K.D. Thompson, E.W. Holmes, and G.S. Read, J. Virol. 66:7146-7152, 1992). All three strains are, therefore, double mutants. To determine the contribution of the UL97 mutation to the high ganciclovir resistance of these mutants, the mutation from the ganciclovir-resistant strain D6/3/1 was transferred to the wild-type strain AD169 to produce the recombinant R6HS. The ganciclovir resistance of R6HS is 4-fold lower than that of D6/3/1 but 10-fold higher than that of AD169. R6HS, like AD169, is sensitive to the nucleotide analogs (S)-1-[(3-hydroxy-2-phosphonylmethoxy) propyl]adenine and (S) 1-[(3-hydroxy-2-phosphonylmethoxy)propyl]cytosine. Ganciclovir phosphorylation in R6HS-infected cells was at the same reduced level as that found in cells infected with the parental mutant D6/3/1. The same G-to-T transversion at nucleotide 1380 in the UL97 coding sequence is present in both R6HS and D6/3/1. This mutation results in the substitution of isoleucine for methionine at amino acid residue 460. In an alignment of the R6HS UL97 amino acid sequence with the amino acid sequences of a wide range of protein kinase family members, methionine 460 lies within a highly conserved region which may function in nucleotide binding and phosphate transfer. PMID- 8207816 TI - The bovine papillomavirus type 1 E5 transforming protein specifically binds and activates the beta-type receptor for the platelet-derived growth factor but not other related tyrosine kinase-containing receptors to induce cellular transformation. AB - The 44-amino-acid E5 protein of bovine papillomavirus type 1 is a highly hydrophobic protein which appears to transform cells through the activation of growth factor receptors. To investigate the specificity of E5-growth factor receptor interactions required for mitogenic signaling, we utilized a nontumorigenic, murine myeloid cell line (32D) which is strictly dependent on interleukin-3 (IL-3) for sustained proliferation in culture. This IL-3 dependence can be functionally substituted by the expression of a variety of surrogate growth factor receptors and the addition of the corresponding ligand. Several receptor cDNAs for the alpha- and beta-type platelet-derived growth factor receptors [alpha PDGFR and beta PDGFR], the epidermal growth factor receptor, and the colony-stimulating factor 1 receptor) were transfected into 32D cells constitutively expressing the E5 protein to test for IL-3-independent growth. Only beta PDGFR was capable of abrogating the IL-3 dependence of 32D cells. The proliferative signal induced by the coexpression of beta PDGFR and E5 was accompanied by stable complex formation between these proteins, constitutive tyrosine phosphorylation of the receptor, and tumorigenicity in nude mice. The lack of cooperative interaction between E5 and the epidermal growth factor receptor, the colony-stimulating factor 1 receptor, and the highly related alpha PDGFR was paralleled by the inability of E5 to bind to these receptors and failure to increase receptor tyrosine phosphorylation. Thus, these data indicate that the ability of E5 to induce sustained proliferation and transformation of 32D cells is a direct consequence of specific interaction between the E5 protein and the beta PDGFR signaling complex and the subsequent stimulation of receptor tyrosine phosphorylation. PMID- 8207817 TI - Functional exchange of an oncoretrovirus and a lentivirus matrix protein. AB - To map functional domains in the retroviral Gag protein we have constructed chimeric viruses where regions of the murine leukemia virus (MuLV) Gag protein have been replaced with analogous sequences from human immunodeficiency virus type 1 (HIV-1). Here we describe the chimeric virus MuLV(MAHIV) which contains the HIV-1 matrix (MA) protein in place of the MuLV MA. MuLV(MAHIV) is infectious but grows at a reduced rate compared with wild-type MuLV. We found that the partial defect in replication of the chimeric virus is at a late stage in the viral life cycle. The MuLV(MAHIV) Gag proteins are distributed aberrantly within cells and are not associated with cellular membranes. Unlike MuLV, HIV-1 is able to integrate into growth-arrested cells. Incorporation of the HIV-1 MA, which is known to play a role in infection of nondividing cells, does not enable MuLV(MAHIV) to be expressed in growth-arrested cells. While it possesses no amino acid homology, we found that the HIV-1 MA can efficiently replace the MuLV matrix protein in infection. PMID- 8207819 TI - Identification and transcriptional regulation of the baculovirus lef-6 gene. AB - We identified an Autographa californica nuclear polyhedrosis virus (AcMNPV) gene, the late expression factor 6 gene (lef-6), which is involved in expression from late and very late AcMNPV gene promoters but not from an early AcMNPV gene promoter in transient expression assays. This gene was located within the PstI I fragment of the AcMNPV genome (14.7 to 17.9 map units), immediately downstream of Ac-iap, the AcMNPV homolog of a baculovirus gene family involved in blocking apoptotic programmed cell death. The nature and temporal regulation of both Ac iap and lef-6 transcripts was examined. Ac-iap and lef-6 were cotranscribed as bicistronic messages at both early and late times postinfection. In addition, lef 6 was transcribed as a monocistronic mRNA by initiation from an early promoter within Ac-iap. PMID- 8207818 TI - The product of the adenovirus intermediate gene IVa2 is a transcriptional activator of the major late promoter. AB - During the course of lytic infection, the adenovirus major late promoter (MLP) is induced to high levels after replication of viral DNA has started. We had previously shown that sequence elements located downstream of the MLP start site were implicated in this late-specific transcriptional activation (DE1, between +85 and +98; DE2, between +100 and +120). Two positive transcription factors involved in this activation have been detected. DEF-A, which specifically binds to DE1 and also to the 3' portion of DE2 (DE2a), and DEF-B, which interacts with the 5' part of DE2 (DE2b). When present together, these two proteins cooperatively assemble onto the DE2 element. We now report the purification of DEF-B and show that it is identical to the product of the adenovirus IVa2 gene product. This conclusion is based on microsequence analysis of DEF-B as well as on the inhibitory effect of antibodies against IVa2 on the DNA-binding activity of DEF-B and also on DE-dependent in vitro transcription. In addition, we show that bacterially synthesized IVa2 protein binds to the DE sequences with the same specificity as DEF-B. Finally, in transfected cells, a recombinant IVa2 protein stimulates MLP activity in a DE-dependent fashion. The physiological implications of these findings are discussed. PMID- 8207820 TI - Expression and subcellular localization of poliovirus VPg-precursor protein 3AB in eukaryotic cells: evidence for glycosylation in vitro. AB - The poliovirus-encoded, membrane-associated VPg-precursor polypeptide 3AB has been implicated in the initiation of viral RNA synthesis. We have expressed 3AB and 3A polypeptides in eukaryotic cells and examined their localization using indirect immunofluorescence and a direct in vitro membrane-binding assay. Results presented here demonstrate that both 3AB and 3A are capable of localizing in the endoplasmic reticulum and the Golgi apparatus in transfected HeLa cells in the absence of any other poliovirus protein. We have also shown that the carboxy terminal 18 amino acids of 3A that constitute an amphipathic domain are important in membrane binding of 3A and 3AB. Additionally, we demonstrate that a significant fraction of both 3A and 3AB can be glycosylated in a membrane dependent fashion during in vitro translation in reticulocyte lysate. We demonstrate that 6-diazo-5-oxo-L-norleucine, an inhibitor of glycoprotein synthesis, significantly inhibits poliovirus RNA synthesis in vivo. The implications of glycosylation of 3AB (and 3A) in viral replication are discussed. PMID- 8207821 TI - A novel cis element essential for stimulated transcription of the p41 promoter of human herpesvirus 6. AB - The p41 DNA-binding protein of human herpesvirus 6 is an apparent processivity factor important for viral DNA replication. The p41 promoter was characterized to understand how this processivity factor is regulated. A single transcription start site and a functional TATA box are located 48 and 74 bp, respectively, upstream of the start codon. A reporter construct containing 1,027 bp of the sequence upstream of the p41 start codon was inactive in uninfected T cells but functioned as a strong promoter in human herpesvirus 6-infected cells. Mutational analysis identified a 21-bp element (the EA site) which is located at -73 to -52 bp relative to the transcription start site and is essential for promoter activity. The ability of the EA site to stimulate transcription optimally appears to be strictly dependent upon its distance from the p41 basal promoter. The EA site contains three overlapping sequences, a CAAT-enhancer-binding protein (C/EBP) transcription factor recognition site and two repeat elements. Mobility shift assays using the EA site identified four binding activities (C1 to C4). C1 and C2 are present in both uninfected and infected cells and do not contain C/EBP factors. In infected cells, point mutation of the EA site abrogates C1 and C2 binding activities and destroys transcriptional activity of the p41 promoter. C3 and C4 are present in uninfected cells only and were found to contain C/EBP factors. These findings indicate that in infected cells, transcriptional stimulation of the p41 promoter by the EA site requires C1 and C2 binding activities. These results further suggest that transcriptional activity may also depend upon the elimination of C3 and C4 binding activities. PMID- 8207822 TI - Expression of a foreign protein by influenza A virus. AB - In this report we describe the rescue of a transfectant influenza A virus which stably expresses a heterologous protein, bacterial chloramphenicol acetyltransferase (CAT). The foreign sequences encoding CAT are expressed as part of an essential influenza virus segment, that coding for the neuraminidase (NA) protein. The novel way by which this was achieved involved inserting in frame the 16-amino-acid self-cleaving 2A protease of foot-and-mouth disease virus between the CAT and the NA coding sequences. The resultant gene produces a polyprotein which is proteolytically cleaved to release both CAT and NA. The intramolecular cleavage occurs at the C terminus of the 2A sequence between a glycine-proline dipeptide motif such that the released NA protein has an additional N-terminal proline residue. The transfectant virus is stable upon passage in tissue culture. CAT activity is expressed at high levels in cell culture supernatants and in the allantoic fluid of infected eggs. Since the chimeric segment must maintain the heterologous reading frame to retain viability, the virus stability is dependent upon concomitant synthesis of the heterologous protein. This design may be particularly appropriate for utilization of influenza virus as a mammalian expression vector. PMID- 8207823 TI - A base-paired structure in the avian sarcoma virus 5' leader is required for efficient encapsidation of RNA. AB - Selective encapsidation of avian sarcoma-leukosis virus genomic RNA within virions requires recognition of a cis-acting signal (termed psi) located in the 5' leader of the RNA between the primer binding site and the splice donor site. Computer analyses indicate the potential for numerous secondary structure interactions within this region, including alternative conformations with similar free energy levels. We have constructed mutations designed to disrupt and restore potential secondary structure interactions within psi to investigate the role of these structures in RNA packaging. To test for the ability of psi mutants to package a heterologous reporter gene into virions, chimeric constructs bearing avian sarcoma virus 5' sequences fused to lacZ were transiently cotransfected with a nonpackageable helper construct into chicken embryo fibroblasts. lacZ virions produced from cotransfected cells were used to infect new cultures of chicken embryo fibroblasts, and then an in situ assay for individual cells expressing lacZ was done. Results obtained with this assay were confirmed in direct analyses of isolated virion RNA by RNase protection assays. Two mutations, predicted to disrupt a potential stem structure forming between elements located at nucleotides 160 to 167 and 227 to 234, severely inhibited packaging when either element was mutated. A construct in which these mutations were combined to restore potential base pairing between the two elements displayed a partially restored packaging phenotype. These results strongly suggest that the structure, referred to as the O3 stem, is required for efficient encapsidation of avian sarcoma virus RNA. Site-directed mutagenesis of additional sequence elements located in the O3 loop reduced packaging as measured by the indirect assay, suggesting that these sequences may also be components of the encapsidation signal. The possible implications of the O3 stem structure with regard to translation of avian sarcoma-leukosis virus short upstream open reading frames are discussed. PMID- 8207824 TI - Three-dimensional structure of vaccinia virus-produced human papillomavirus type 1 capsids. AB - The capsid proteins of papillomavirus self-assemble to form empty capsids or virus-like particles that appear quite similar to naturally occurring virions by conventional electron microscopy. To characterize such virus-like particles more fully, cryoelectron microscopy and image analysis techniques were used to generate three-dimensional reconstructions of capsids produced by vaccinia virus recombinants (V capsids) that expressed human papillomavirus type 1 L1 protein only or both L1 and L2 proteins. All V capsids had 72 pentameric capsomers arranged on a T = 7 icosahedral lattice. Each particle (approximately 60 nm in diameter) consisted of an approximately 2-nm-thick shell of protein with a radius of 22 nm with capsomers that extend approximately 6 nm from the shell. At a resolution of 3.5 nm, both V capsid structures appear identical to the capsid structure of native human papillomavirus type 1 (T. S. Baker, W. W. Newcomb, N. H. Olson, L. M. Cowsert, C. Olson, and J. C. Brown, Biophys. J. 60:1445-1456, 1991), thus implying that expressed and native capsids are structurally equivalent. PMID- 8207825 TI - First peptide vaccine providing protection against viral infection in the target animal: studies of canine parvovirus in dogs. AB - A synthetic peptide vaccine which protects dogs against challenge with virulent canine parvovirus is described. The amino acid sequence used was discovered in previous studies on the immunogenic properties of previously mapped antigenic sites and represents the amino-terminal region of viral protein VP2. As with marker vaccines, it is possible to discriminate between vaccinated dogs that have not been exposed to the virus and dogs that have been infected with the virus. The protective mechanism can be explained by a humoral response against the peptide aided by T-cell epitopes contained in the carrier protein used for peptide coupling. This is the first example of a synthetic peptide vaccine that induces protection in target animals. PMID- 8207826 TI - Mutations in accessory DNA replicating functions alter the relative mutation frequency of herpes simplex virus type 1 strains in cultured murine cells. AB - The contribution of the herpes simplex virus type 1 (HSV-1)-encoded uracil DNA glycosylase (UNG), thymidine kinase (TK), and dUTPase to the relative mutant frequency (RMF) of the virus in cultured murine cells was examined. A panel of HSV-1 mutants that lacked singly or doubly the UNG, TK, or dUTPase activity were generated by disruption of the enzyme coding regions with the Escherichia coli beta-galactosidase (beta-gal) gene in strain 17syn+. To establish a baseline RMF of strain 17syn+, the beta-gal gene was inserted into the UL3 locus. In all of the viruses, the beta-gal insert served as a phenotypic marker of RMF. A mutant plaque was identified by the lack of beta-gal activity and, in selected cases, positive in situ hybridization for beta-gal sequences. Replication kinetics in NIH 3T3 cells demonstrated that all of the mutants replicated efficiently, generating stocks with equivalent titers. Two independently generated UL3-beta gal viruses were examined and established a baseline RMF of approximately 0.5% in both NIH 3T3 and LM TK- cells. Loss of dUTPase activity resulted in viruses with fivefold-increased RMFs, indicating that the HSV-1 dUTPase has an antimutator function. The RMF observed for the tk- viruses was reduced as much as 40-fold (RMF of 0.02%), suggesting that the viral TK is a mutator activity. The RMF of two independent UNG- viruses showed no significant difference from the baseline RMF in limited passage; however, following successive passage, the data suggested that UNG activity serves as an antimutator. These results have implications for the natural history of HSV and the development of antiviral therapies. PMID- 8207827 TI - Bgp2, a new member of the carcinoembryonic antigen-related gene family, encodes an alternative receptor for mouse hepatitis viruses. AB - Murine coronaviruses such as mouse hepatitis virus (MHV) infect mouse cells via cellular receptors that are isoforms of biliary glycoprotein (Bgp) of the carcinoembryonic antigen gene family (G. S. Dveksler, C. W. Dieffenbach, C. B. Cardellichio, K. McCuaig, M. N. Pensiero, G.-S. Jiang, N. Beauchemin, and K. V. Holmes, J. Virol. 67:1-8, 1993). The Bgp isoforms are generated through alternative splicing of the mouse Bgp1 gene that has two allelic forms called MHVR (or mmCGM1), expressed in MHV-susceptible mouse strains, and mmCGM2, expressed in SJL/J mice, which are resistant to MHV. We here report the cloning and characterization of a new Bgp-related gene designated Bgp2. The Bgp2 cDNA allowed the prediction of a 271-amino-acid glycoprotein with two immunoglobulin domains, a transmembrane, and a putative cytoplasmic tail. There is considerable divergence in the amino acid sequences of the N-terminal domains of the proteins coded by the Bgp1 gene from that of the Bgp2-encoded protein. RNase protection assays and RNA PCR showed that Bgp2 was expressed in BALB/c kidney, colon, and brain tissue, in SJL/J colon and liver tissue, in BALB/c and CD1 spleen tissue, in C3H macrophages, and in mouse rectal carcinoma CMT-93 cells. When Bgp2 transfected hamster cells were challenged with MHV-A59, MHV-JHM, or MHV-3, the Bgp2-encoded protein served as a functional MHV receptor, although with a lower efficiency than that of the MHVR glycoprotein. The Bgp2-mediated virus infection could not be inhibited by monoclonal antibody CC1 that is specific for the N terminal domain of MHVR. Although CMT-93 cells express both MHVR and Bgp2, infection with the three strains of MHV was blocked by pretreatment with monoclonal antibody CC1, suggesting that MHVR was the only functional receptor in these cells. Thus, a novel murine Bgp gene has been identified that can be coexpressed in inbred mice with the Bgp1 glycoproteins and that can serve as a receptor for MHV strains when expressed in transfected hamster cells. PMID- 8207828 TI - The membrane-associated and secreted forms of the respiratory syncytial virus attachment glycoprotein G are synthesized from alternative initiation codons. AB - Respiratory syncytial (RS) virus synthesizes two mature forms of its attachment glycoprotein G: an anchored type II integral membrane form and a smaller form that is secreted into the medium. Here we demonstrate that these two forms are synthesized as distinct primary translation products of a single species of G protein mRNA by initiation at either of two different AUGs. Mutant cDNAs which eliminated one of the other of the two AUG codons near the 5' end of the G gene open reading frame were constructed. Analysis of the proteins synthesized from these cDNAs, either by translation of transcripts in a cell-free system or in cells infected with recombinant vaccinia viruses containing either one of the mutant cDNAs, showed that elimination of either the first or the second of these AUG codons abrogated the synthesis of the membrane-anchored or the secreted form of the protein, respectively. Additionally, two unglycosylated forms of G protein which comigrated with the unglycosylated G proteins expressed by these recombinant viruses were detected in RS virus-infected cells. Since the second AUG encodes a methionine residue that lies near the middle of the signal/anchor domain, initiation at this codon resulted in a protein with a hydrophobic amino terminus. This form of the glycoprotein was efficiently secreted from cells infected with the vaccinia virus recombinant, and the amino-terminal sequence of this protein was identical to that of G protein secreted from RS virus-infected cells. Our results demonstrate that the secreted form of RS virus G protein is produced by initiation at the second AUG codon of the G open reading frame, followed by proteolytic removal of the signal/anchor domain. PMID- 8207829 TI - Reconstitution of Flock House provirions: a model system for studying structure and assembly. AB - Assembly of Flock House virus in infected Drosophila cells proceeds through an intermediate, the provirion, which lacks infectivity until the coat precursor protein, alpha, undergoes a spontaneous "maturation" cleavage (A. Schneemann, W. Zhong, T. M. Gallagher, and R. R. Rueckert, J. Virol 6:6728, 1992). We describe here methods for purifying provirions in a state which permitted dissociation and reassembly. Dissociation, to monomeric alpha protein and free RNA, was accomplished by freezing at pH 9.0 in the presence of 0.5 M salt and 0.1 M urea. When dialyzed at low ionic strength and pH 6.5, the dissociation products reassembled spontaneously to form homogeneous provirions with a normal complement of RNA as judged by cosedimentation with authentic virions and by ability to undergo maturation cleavage with acquisition of substantial, though subnormal, infectivity. Reconstitution experiments, i.e., remixing components after separating RNA from capsid protein, generated abnormal particles, suggesting the presence in the unfractionated dissociation products of an unidentified "nucleating" component. PMID- 8207830 TI - Coordinate regulation of replication and virus assembly by the large envelope protein of an avian hepadnavirus. AB - We have used linker scanning and site-directed mutagenesis in an attempt to distinguish among the known functions of the duck hepatitis B virus large envelope protein, p36. We found that linker-encoded amino acid substitutions in at least one region of the pre-S envelope protein p36 produced defects in both the production of enveloped virus and the regulation of covalently closed circular DNA (cccDNA) synthesis. Most linker substitutions, typically in the 5' two-thirds of the pre-S region of the p36 gene did not affect either cccDNA regulation or enveloped virus production but did destroy the infection competence of the enveloped particles produced. Single amino acid substitutions of residues 128 and 131 demonstrated a similar correlation between defects in the ability of p36 to support enveloped virus production and to control cccDNA levels. We concluded from these studies that virus production and cccDNA regulation probably require a common activity of p36. PMID- 8207831 TI - Serum neutralization of feline immunodeficiency virus is markedly dependent on passage history of the virus and host system. AB - Sera from feline immunodeficiency virus (FIV)-infected cats exhibited extremely low levels of neutralizing antibodies against virus passaged a few times in vitro (low passage), when residual infectivity was assayed in the CD3+ CD4- CD8- MBM lymphoid cell line or mitogen-activated peripheral blood mononuclear cells. By sharp contrast, elevated titers of highly efficient neutralizing activity against FIV were measured, by use of high-passage virus, in assays on either the fibroblastoid CrFK or MBM cell line. However, high-passage virus behaved the same as low-passage virus after one in vivo passage in a specific-pathogen-free cat and reisolation. Subneutralizing concentrations of infected cat sera enhanced the production of low-passage virus by MBM cells, an effect not seen with high passage virus in CrFK cells. These qualitative and quantitative discrepancies could not be attributed to differences in the amount of immunoreactive viral material, to the amount of infectious virus present in the viral stocks, or to the presence of anti-cell antibodies. The observed effects were most likely due to the different passage history of the viral preparations used. The observation that neutralizing antibodies detected with high-passage virus were broadly cross reactive in assays with CrFK cells but isolate specific in MBM cells suggests also that the cell substrate can influence the result of FIV neutralization assays. This possibility could not be tested directly because FIV adapted to grow in CrFK cells had little infectivity for lymphoid cells and vice versa. In vitro exposure to infected cat sera had little or no effect on the ability of in vivo passaged FIV to infect cats. These data reveal no obvious relationship between titers against high-passage virus and ability to block infectivity of FIV in cats and suggest caution in the use of such assays to measure vaccine efficacy. In conclusion, by contrast with what has been previously reported for the use of CrFK cells and high-passage virus, both natural and experimental infections of cats with FIV generate poor neutralizing antibody responses with regard to in vivo protection. PMID- 8207832 TI - Completion of Kunjin virus RNA sequence and recovery of an infectious RNA transcribed from stably cloned full-length cDNA. AB - Completion of the Kunjin virus (KUN) RNA sequence showed that it is the longest flavivirus sequence reported (11,022 bases), commencing with a 5' noncoding region of 96 bases. The 3' noncoding sequence of 624 nucleotides included a unique insertion sequence of 46 bases adjacent to the stop codon, but otherwise it had properties similar to those of RNAs of closely related flaviviruses. A full-length KUN cDNA clone which could be stably propagated in Escherichia coli DH5 alpha was constructed; SP6 polymerase RNA transcripts from amplified cDNA were infectious when transfected into BHK-21 cells. A mutational change abolishing the BamHI restriction site at position 4049, leading to a conservative amino acid change of Arg-175 to Lys in the NS2A protein, was introduced into the cDNA during construction and was retained in the recovered virus. Extra terminal nucleotides introduced during cloning of the cDNA were shown to be present in the in vitro RNA transcripts but absent in the RNA of recovered virus. Although recovered virus differed from the parental KUN by a smaller plaque phenotype and delayed growth rate in BHK-21 cells and mice, it was very similar as assessed by several other criteria, such as peak titer during growth in cells, infectivity titer in cells and in mice, rate of adsorption and penetration in cells, replication at 39 degrees C, and neurovirulence after intraperitoneal injection in mice. The KUN stably cloned cDNA will provide a useful basis for future studies in defining and characterizing functional roles of all the gene products. PMID- 8207833 TI - In vivo leukocyte tropism of bovine leukemia virus in sheep and cattle. AB - Bovine leukemia virus (BLV), an oncovirus related to human T-cell leukemia virus type I, causes a B-cell lymphoproliferative syndrome in cattle, leading to an inversion of the T-cell/B-cell ratio and, more rarely, to a B-cell lymphosarcoma. Sheep are highly sensitive to BLV experimental infection and develop B-cell pathologies similar to those in cattle in 90% of the cases. BLV tropism for B cells has been well documented, but the infection of other cell populations may also be involved in the BLV-induced lymphoproliferative syndrome. We thus looked for BLV provirus in other leukocyte populations in sheep and cattle by using PCR. We found that while B cells harbor the highest proviral load, CD8+ T cells, monocytes, and granulocytes, but not CD4+ T cells, also bear BLV provirus. As previously described, we found that persistent lymphocytosis in cows is characterized by an expansion of the CD5+ B-cell subpopulation but we did not confirm this observation in sheep in which the expanded B-cell population expressed the CD11b marker. Nevertheless, BLV could be detected both in bovine CD5+ and CD5- B cells and in sheep CD11b+ and CD11b- B cells, indicating that the restricted BLV tropism for a specific B-cell subpopulation cannot explain its expansion encountered in BLV infection. Altogether, this work shows that BLV tropism in leukocytes is wider than previously thought. These results lead the way to further studies of cellular interactions among B cells and other leukocytes that may intervene in the development of the lymphoproliferative syndrome induced by BLV infection. PMID- 8207834 TI - Identification of human T-cell lymphotropic virus type I 21-base-pair repeat specific and glial cell-specific DNA-protein complexes. AB - The human T-cell lymphotropic virus type I (HTLV-I)-encoded protein, Tax, is capable of trans-activating HTLV-I transcription by interacting with specific sequences in the HTLV-I long terminal repeat (LTR) which comprise an inducible enhancer containing three imperfect tandem repeats of a 21-bp sequence. There is no evidence that purified Tax can bind to DNA in the absence of cellular factors, suggesting that Tax most likely regulates transcription via interaction with cellular factors. Since HTLV-I is a documented agent of adult T-cell leukemia and tropical spastic paraparesis, disorders of the immune and nervous systems, respectively, characterization of cellular factors of lymphoid and neuroglial origin which interact with the 21-bp repeat elements is essential to understanding of the mechanisms involved in basal and Tax-mediated transcription in cells of immune and nervous system origin. Utilizing electrophoretic mobility shift (EMS) analyses, we have detected both 21-bp repeat-specific and glial cell specific DNA-protein complexes. Several 21-bp repeat-specific DNA-protein complexes were detected when nuclear extracts derived from cells of lymphoid (Jurkat, SupT1, and H9), neuronal (IMR-32 and SK-N-MC), and glial (U-373 MG, Hs683, and U-118) origin were used in reactions with each of the three 21-bp repeat elements. In addition, a glial cell-specific DNA-protein complex was detected when nuclear extracts derived from U-373 MG, Hs683, and U-118 glial cell lines reacted with the promoter-distal and central 21-bp repeat elements. Furthermore, EMS analyses performed with nuclear extracts derived from lymphocytic and glial cell origin and a 223-bp fragment of the HTLV-I long terminal repeat encompassing the three 21-bp repeat elements (designated Tax responsive elements 1 and 2, TRE-1/-2) have also resulted in the detection of glial cell type-specific DNA-protein complexes. Competition EMS analyses with oligonucleotides containing transcription factor binding site sequences indicate the involvement of a cyclic AMP response element binding protein in the formation of DNA-protein complexes which form with all three 21-bp repeat elements and the glial cell-specific DNA-protein complex as well as the involvement of Sp1 or an Sp1-related factor in the formation of the 21-bp repeat III-specific DNA-protein complexes. PMID- 8207835 TI - Modifications in the binding domain of avian retrovirus envelope protein to redirect the host range of retroviral vectors. AB - On the basis of theoretical structural and comparative studies of various avian leukosis virus SU (surface) envelope proteins, we have identified four small regions (I, II, III, and IV) in their receptor-binding domains that could potentially be involved in binding to receptors. From the envelope gene of an avian leukosis virus of subgroup A, we have constructed a set of SU mutants in which these regions were replaced by the coding sequence of FLA16, a 16-amino acid RGD-containing peptide known to be the target for several cellular integrin receptors. Helper-free retroviral particles carrying a neo-lacZ retroviral vector were produced with the mutant envelopes. SU mutants in which regions III and IV were substituted yielded normal levels of envelope precursors but were not detectably processed or incorporated in viral particles. In contrast, substitutions in regions I and II did not affect the processing and the viral incorporation of SU mutants. When FLA16 was inserted in region II, it could be detected with antibodies against FLA16 synthetic peptide, but only when viral particles were deglycosylated. Viral particles with envelopes mutated in region I or II were able to infect avian cells through the subgroup A receptor at levels similar to those of the wild type. When viruses with envelopes containing FLA16 peptide in region II were applied to plastic dishes, they were found to promote binding of mammalian cells resistant to infection by subgroup A avian leukosis viruses but expressing the integrins recognized by FLA16. Deglycosylated helper free viruses obtained by mild treatment with N-glycosidase F have been used to infect these mammalian cells, and infections have been monitored by neomycin selection. No neomycin-resistant clones could be obtained after infection by viruses with wild-type envelopes. Conversely, colonies were obtained after infection by viruses with envelopes bearing FLA16 in region II, and the genome of the retroviral vector was found correctly integrated in cell DNA of these colonies. By using a blocking peptide containing the minimal adhesive RGD sequence contained in FLA16, we have shown that preincubation of target cells could specifically inhibit infection by viruses with FLA16. PMID- 8207836 TI - Postassembly cleavage of a retroviral glycoprotein cytoplasmic domain removes a necessary incorporation signal and activates fusion activity. AB - Viral protease-mediated cleavage within the cytoplasmic domain of the transmembrane (TM) glycoprotein of the type D retrovirus, Mason-Pfizer monkey virus, removes approximately 16 amino acids from the carboxy terminus of the protein. To determine the functional significance of this cleavage in the virus life cycle, we introduced premature stop codons into the TM coding domain, resulting in the production of truncated glycoproteins. Progressive truncated of the cytoplasmic domain identified the carboxy-terminal third as being required for efficient incorporation of the glycoprotein complex into budding virions and profoundly increased the fusogenic capability of the TM glycoprotein. These results, together with the ability of matrix protein mutations to suppress TM cleavage, imply that this portion of the glycoprotein interacts specifically with the capsid proteins during budding, suppressing glycoprotein fusion function until virus maturation has occurred. PMID- 8207837 TI - Platelet-activating factor: a candidate human immunodeficiency virus type 1 induced neurotoxin. AB - The pathogenesis of central nervous system disease during human immunodeficiency virus type 1 (HIV-1) infection revolves around productive viral infection of brain macrophages and microglia. Neuronal losses in the cortex and subcortical gray matter accompany macrophage infection. The question of how viral infection of brain macrophages ultimately leads to central nervous system (CNS) pathology remains unanswered. Our previous work demonstrated high-level production of tumor necrosis factor alpha, interleukin 1 beta, arachidonic acid metabolites, and platelet-activating factor (PAF) from HIV-infected monocytes and astroglia (H. E. Gendelman, P. Genis, M. Jett, and H. S. L. M. Nottet, in E. Major, ed., Technical Advances in AIDS Research in the Nervous System, in press; P. Genis, M. Jett, E. W. Bernton, H. A. Gelbard, K. Dzenko, R. Keane, L. Resnick, D. J. Volsky, L. G. Epstein, and H. E. Gendelman, J. Exp. Med. 176:1703-1718, 1992). These factors, together, were neurotoxic. The relative role(s) of each of these candidate neurotoxins in HIV-1-related CNS dysfunction was not unraveled by these initial experiments. We now report that PAF is produced during HIV-1-infected monocyte astroglia interactions. PAF was detected at high levels in CSF of HIV-1-infected patients with immunosuppression and signs of CNS dysfunction. The biologic significance of the results for neurological disease was determined by addition of PAF to cultures of primary human fetal cortical or rat postnatal retinal ganglion neurons. Here, PAF at concentrations of > or = 300 pg/ml produced neuronal death. The N-methyl-D-aspartate receptor antagonist MK-801 or memantine partially blocked the neurotoxic effects of PAF. The identification of PAF as an HIV-1-induced neurotoxin provides new insights into how HIV-1 causes neurological impairment and how it may ultimately be ameliorated. PMID- 8207839 TI - Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. AB - Virologic and immunologic studies were performed on five patients presenting with primary human immunodeficiency virus type 1 (HIV-1) infection. CD8+ cytotoxic T lymphocyte (CTL) precursors specific for cells expressing antigens of HIV-1 Gag, Pol, and Env were detected at or within 3 weeks of presentation in four of the five patients and were detected in all five patients by 3 to 6 months after presentation. The one patient with an absent initial CTL response had prolonged symptoms, persistent viremia, and low CD4+ T-cell count. Neutralizing antibody activity was absent at the time of presentation in all five patients. These findings suggest that cellular immunity is involved in the initial control of virus replication in primary HIV-1 infection and indicate a role for CTL in protective immunity to HIV-1 in vivo. PMID- 8207840 TI - Inhibition of p53-mediated transactivation by E6 of type 1, but not type 5, 8, or 47, human papillomavirus of cutaneous origin. AB - Transient transfection experiments indicated (i) that E6 protein of non-cancer associated cutaneous human papillomavirus type 1 (HPV-1) can inhibit p53-mediated transcriptional transactivation in both p53-deficient human cells (H358) and normal rat cells (3Y1), but those of cancer-associated cutaneous HPV-5, -8, and 47 cannot do so in either H358 or 3Y1 cells, and (ii) that E6 proteins of HPV-16 and -18 can inhibit the p53 function in H358 cells but not in 3Y1 cells. PMID- 8207841 TI - Changes in the cytopathic effects of human immunodeficiency virus type 1 associated with a single amino acid alteration in the ectodomain of the gp41 transmembrane glycoprotein. AB - A human immunodeficiency virus type 1 mutant with a single amino acid change (designated 596 W/M) in the ectodomain of the gp41 transmembrane envelope glycoprotein replicated in T-cell lines and in CD4-positive peripheral blood mononuclear cells identically to the wild-type virus. However, the cytopathic effects associated with infection by the mutant virus were altered, with a marked attenuation of syncytium formation and a significant delay in single-cell lysis relative to those of the wild-type virus-infected culture. The 596 W/M mutant is apparently defective in a function that is dispensable for virus entry but that contributes to the efficiency of induction of viral cytopathic effects. PMID- 8207842 TI - Anomalous transforming behavior of a bovine papillomavirus type 1 mutant with an upstream promoter mutation. AB - We show that the previously described high-transformation phenotype of the bovine papillomavirus type 1 mutant BPV730 is manifested only in an E6-dependent cell transformation assay. The BPV730 mutation was associated with superinduction of the putative E6 promoter, P89, after cycloheximide treatment, and with reduced activity of the P3080 promoter. PMID- 8207838 TI - Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences. AB - Human immunodeficiency virus (HIV) dementia is a common clinical syndrome of uncertain pathogenesis in patients with AIDS. In several animal models of retrovirus-induced brain disease, specific viral envelope sequences have been found to influence the occurrence of central nervous system disease. Therefore, to search for unique envelope sequences correlated with HIV dementia, we studied 22 HIV-infected patients who were neurologically assessed premortem and classified into demented (HIVD) (n = 14) and nondemented (ND) (n = 8) groups. Using DNA from autopsied brain and spleen, we amplified, cloned, and sequenced a 430-nucleotide region including the V3 loop and flanking regions. All brain derived clones in both clinical groups showed marked homology to the macrophage tropic consensus sequence within the V3 loop. Two amino acid positions within (position 305) and outside (position 329) the V3 region showed significant divergence between the two clinical groups. At position 305, a histidine was predominant in the HIVD group and was not observed in the ND group, but a proline was predominant in the ND group and was not observed in the HIVD group. Similarly, at position 329, a leucine was predominant in the HIVD group but rarely observed in the ND group, whereas an isoleucine was predominant in the ND group at this position. In addition, the HIVD group had 21 amino acid residues at specific positions that were unique relative to the ND group, whereas only 2 residues at specific positions were unique to the ND group. These data suggest that distinct HIV envelope sequences are associated with the clinical expression of HIV dementia. PMID- 8207843 TI - A baculovirus gene involved in late gene expression predicts a large polypeptide with a conserved motif of RNA polymerases. AB - We have identified and sequenced a novel baculovirus gene, late expression factor eight gene (lef-8), of Autographa californica nuclear polyhedrosis virus that is necessary for efficient expression from late and very late virus gene promoters in a transient expression assay. The predicted gene product, LEF-8, has a molecular mass of 102 kDa and contains a conserved sequence motif, GXKX4HGQ/NKG, found in DNA-directed RNA polymerases throughout the animal, plant, and microbial kingdoms. PMID- 8207844 TI - Adoptive transfer of polyclonal and cloned cytolytic T lymphocytes (CTL) specific for mouse AIDS-associated tumors is effective in preserving CTL responses: a measure of protection against LP-BM5 retrovirus-induced immunodeficiency. AB - Cytolytic T lymphocytes (CTL) can be raised against C57BL/6 B-cell lymphomas from mice with LP-BM5 murine leukemia virus-induced AIDS (MAIDS). Adoptive transfer of polyclonal anti-MAIDS tumor CTL or two CTL clones specific for the B6-1710 MAIDS lymphoma caused preservation of major histocompatibility complex-restricted and allogeneic CTL responses, which may be interpreted as indices of protection from LP-BM5 murine leukemia virus-induced immunodeficiency. PMID- 8207845 TI - Heat shock response to vaccinia virus infection. AB - We have investigated the induction of heat shock proteins (HSPs) in mice infected with vaccinia virus. Vaccinia virus replicates to high levels in the ovaries of infected mice and causes a significant inhibition of host cell DNA, RNA, and protein synthesis. Many HSPs are constitutively expressed in murine ovarian tissue at low levels, consistent with their obligatory role in normal physiological events. In contrast with these events, HSP expression was augmented in virus-infected mouse ovaries 6 days postinfection. In particular, there was a dramatic increase in the expression of a protein identified as the inducible 72 kDa HSP. Analysis of cellular mRNA confirmed this protein to be the major mouse inducible HSP70 and demonstrated its presence within virus-infected cells. Hence, we have demonstrated the expression of stress proteins during poxvirus infection in vivo. PMID- 8207846 TI - Formation of empty B19 parvovirus capsids by the truncated minor capsid protein. AB - We previously reported that empty capsids of B19 parvovirus were formed by the major capsid protein (VP2) alone expressed in a baculovirus system, but the minor capsid protein (VP1), longer by 227 amino acids, alone did not form empty capsids. We report here further investigations of the constraints on capsid formation by truncated versions of VP1. Studies were performed with recombinant baculoviruses expressed in Sf9 cells. Severely shortened VP1, extended beyond the VP2 core sequence by about 70 amino acids of the unique region, formed capsids normal in appearance; longer versions of VP1 also formed capsids but did so progressively less efficiently and produced capsids of more markedly dysmorphic appearance as the VP1-unique region was lengthened. PMID- 8207847 TI - Stimulation of virus production and induction of self-syncytium formation in human T-cell leukemia virus type I- and type II-infected T cells by 12-O tetradecanoylphorbol-13-acetate. AB - Treatment of human T-cell leukemia virus type I (HTLV-I)- and HTLV-II-infected T cell lines with 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated virus release. However, this stimulation was mainly detected at 42 to 48 h of treatment, whereas later virus release declined rapidly. During the first 48 h, TPA had no effect on cell growth, but later, the number of viable cells was profoundly lower in the TPA-treated than in the untreated cultures. This shift in virus release and cell number resulted from self-fusion of a large proportion of the virus-producing cells, which seemed to consequently enter into a dying process. This fusion, which resulted in syncytium formation, was strongly inhibited by anti-HTLV-I env monoclonal antibodies. Furthermore, no self-fusion was detected in three different uninfected T-cell lines similarly treated with TPA. On the other hand, stimulation of virus production by 3-methylcholanthrene (3-MC) treatment failed to induce self-fusion in the infected cells. Moreover, no syncytium was detected when these 3-MC-treated infected cells were cocultured with any of the TPA-treated uninfected cells. The effects of TPA on virus production and syncytium formation were both abolished by three different protein kinase C inhibitors. Taken together, these data suggest that the self-fusion observed in these experiments required both enhanced virus production and protein kinase C-phosphorylated viral or/and virally induced cellular component(s). PMID- 8207849 TI - HC Blue No. 1. PMID- 8207848 TI - CI Acid Orange 3. PMID- 8207850 TI - HC Blue No. 2. PMID- 8207851 TI - HC Red No. 3. PMID- 8207852 TI - HC Yellow No. 4. PMID- 8207853 TI - 2-Amino-4-nitrophenol. PMID- 8207854 TI - 2-Amino-5-nitrophenol. PMID- 8207855 TI - 1,4-Diamino-2-nitrobenzene (2-nitro-para-phenylenediamine). PMID- 8207856 TI - D&C Red No. 9 (CI Pigment Red 53:1). PMID- 8207857 TI - Magenta and CI Basic Red 9. PMID- 8207858 TI - CI Direct Blue 15. PMID- 8207859 TI - CI Acid Red 114. PMID- 8207860 TI - CI Pigment Red 3. PMID- 8207861 TI - 4,4'-Methylenebis(2-chloroaniline) (MOCA). PMID- 8207862 TI - para-Chloroaniline. PMID- 8207863 TI - 2,6-Dimethylaniline (2,6-xylidine). PMID- 8207864 TI - N,N-dimethylaniline. PMID- 8207865 TI - Occupational exposures of hairdressers and barbers and personal use of hair colourants. PMID- 8207866 TI - [Characteristic features of the heart disease in the elderly]. AB - Pathologic aspects of cardiac aging, and heart diseases as extreme type of aging in the elderly were discussed. 1) Aging of the myocardium: Myocardial hypertrophy does not occur in the normal elderly who do not have heart diseases, most of them ranged between 200 and 350 gm. Amyloid deposit was frequently found in elderly heart (20 to 40%), but cardiac amyloidosis with cardiac symptoms was infrequent (0.2%). 2) Aging of the cardiac valves. Cardiac valves are easily influenced by the mechanical stimuli by incessant valve motion. The circumference of the valves has a tendency to become dilated by aging, especially the aortic valve. Some developed aortic regurgitation. Valvular calcification was marked in the mitral ring, inducing mitral ring calcification, which is found in about 10% of autopsy cases and may cause mitral regurgitation in cases of calcification extending for a length of more than 30 mm. Aortic valves showed calcification in 7% of autopsy cases, causing calcific aortic stenosis in severe cases. 3) Aging of the coronary arteries. The coronary stenotic index was defined as the sum of the highest count of 3 major coronary arteries (point 5 for 100% obstruction, 4 for 75% stenosis and 3 for 50% stenosis etc.). The incidence of myocardial infarction in the group with a stenotic index of more than 9 was markedly higher than in a group with an index of less than 8. 4) Aging of the conduction system. Numeral decrease of conduction cells in the sinoatrial node of the aged was shown by a color image analyzer, which was less severe than cases of sick sinus syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8207867 TI - [The etiology and management of congestive heart failure in the elderly]. AB - The common underlying heart diseases were ischemic heart disease (39%), valvular heart disease (27%), hypertensive heart disease (10%) in 104 patients (mean age 79 yrs) with congestive heart failure (CHF). Cardiomyopathy (5%) and congenital heart disease (2%) such as atrial septal defect were less common. In addition, many extracardiac diseases including anemia, hypothyroidism, renal failure and pulmonary disease contributed to the etiology of CHF in the elderly. Cardiac amyloidosis should be considered as an uncommon cause of refractory CHF. While the precipitating factor was not found in half of the 104 patients with CHF, the most common factors were respiratory infection, myocardial ischemia and arrhythmia. In addition, inappropriate drug usage including poor drug compliance, the use of beta-blockers and excessive intake of sodium and fluid precipitated or exacerbated heart failure. Renal failure was a most important complication and predisposed to refractory CHF. Aged patients with mild CHF (NYHA class II) showed an insufficient production of cyclic AMP and GMP in proportion to the increases of norepinephrine and atrial natriuretic peptide in comparison with health aged subjects after the submaximal treadmill exercise test. This finding may suggest that an inadequate compensation of neurohumoral factors is prone to cause CHF in the elderly. Appropriate management of acute CHF in the elderly begins with recognition of the underlying heart disease, complications and the severity of cardiac function. In addition to medical management including loop diuretics, vasodilator, beta-receptor agonist and phosphodiesterase inhibitor, cases associated with respiratory and renal failure require mechanical ventilation and continuous hemofiltration. PMID- 8207868 TI - [Antiarrhythmic therapy in the elderly]. AB - It has been widely recognized that the elderly shows an increased prevalence of cardiac arrhythmias. Moreover, the elderly population presents a number of problems to the clinician prescribing antiarrhythmics, such as drug accumulation, low compliance and proarrhythmias. In this article, we discussed age-related changes of the pharmacokinetics and the pharmacodynamics of antiarrhythmics with reference to proarrhythmia in the elderly. Age-dependent decrease of renal creatinine clearance plays an important role in the pharmacokinetics in the elderly. Age-related changes of pharmacodynamics of antiarrhythmics have not been evaluated extensively. Our results concerning the effect of class 1a drug on filtered QRS width on signal-averaged ECG, demonstrated age-related accentuation of class 1 action. In terms of non-pharmacologic treatment, physiological pacing is useful especially on elderly patients. The indications for catheter ablation and implantable cardiverter-defibrillators for the elderly should be established in detail. PMID- 8207869 TI - [Surgical indications and prognosis of valvular heart disease and infective endocarditis in the elderly]. AB - To elucidate the surgical results and long-term prognosis in valvular heart disease, including infective endocarditis, in the elderly, 110 patients with valvular heart disease who underwent surgical treatment and 29 patients with infective endocarditis were studied. Among the patients with valvular heart disease, 52 patients (21 elderly, 31 young) underwent aortic valve replacement, 46 patients (24 elderly, 22 young) mitral valve replacement, and 12 patients (6 elderly, 6 young) double valve replacement. There were only 2 operative deaths (1 elderly, 1 young). The 5-year survival rate was 91.2% in elderly patients and 92.3% in younger patients. The five-year event-free rate was 67.3% in elderly patients and 79.0% in younger patients. Among 29 patients with infective endocarditis, surgical treatment was successfully performed in six of the 13 elderly patients and 10 of the 16 younger patients. There were two deaths among the younger patients and no death among the elderly patients, although recurrence was found in 2 elderly patients. Good results can be obtained from surgical intervention in elderly patients, provided they are risk-stratified before surgery followed by appropriate management. PMID- 8207870 TI - [Characteristics of myocardial diseases in the elderly]. AB - Myocardial diseases consist of cardiomyopathy of unknown origin and specific myocardial diseases of known origin. The former consists mainly of dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). In the latter, cardiac amyloidosis may be most frequently seen in the elderly. One hundred and twenty patients with cardiomyopathy were studied concerning their clinical courses. They were divided into 2 groups; i) young-middle-aged (Y) and ii) elderly (0). Group 1 was divided into 2 subgroups: 1a) followed up to an age less than 60 years old, and 1b) followed up to beyond age 60. In DCM, left ventricular posterior wall thickness and left atrial diameter increased significantly in the elderly. In HCM, young patients had obstructive type disease more frequently than the elderly. A history of mild hypertension was found more frequently in the middle-aged or elderly than in the young. Left ventricular end-diastolic diameter increased and left ventricular wall thickness decreased significantly in the elderly. Many patients with DCM usually die of congestive heart failure with ventricular arrhythmia, and those with HCM, both young or middle-aged, often die suddenly during sports activity. If there is an adaptive system, such as increased wall thickness in DCM or decreased wall thickness and increased diameter in HCM, which may contribute to the normalization of left ventricular wall stress, the patients might be able to survive to old age. PMID- 8207871 TI - [Early treatment in acute myocardial infarction for elderly patients]. PMID- 8207872 TI - [Plasma fibrinogen as a cardiovascular risk factor]. AB - Recent prospective epidemiological studies have shown that plasma fibrinogen is a powerful, independent risk factor of arteriosclerotic diseases such as ischemic heart disease, stroke and peripheral vascular disease. Cross-sectional studies have shown correlation of fibrinogen with various factors, including age, gender, race and smoking. Plasma fibrinogen strongly affects blood coagulation, blood rheology and platelet aggregation. In addition, fibrinogen, fibrin and their degradation products have direct effects on the vascular wall. The migration of vascular smooth muscle cells from the media into the intima and their proliferation play an important role in the pathogenesis of atherosclerosis and in the organization of thrombi. Smooth muscle cells adhere to substrate-bound fibrinogen/fibrin. The cells migrate to a gradient of soluble fibrinogen (chemotaxis). The cells also migrate in a dose-dependent manner to a gradient of substrate-bound fibrinogen and fibrin (haptotaxis). The relation among hyperfibrinogenemia, atherosclerosis and thrombosis is highly complicated. There is no prospective study on fibrinogen and cardiovascular disorders among Japanese. Studying plasma fibrinogen to predict cardiovascular disorders may provide some new insight into their pathophysiological mechanisms. PMID- 8207873 TI - [Circadian profiles of blood pressure with respect to age]. AB - The effects of ageing on nocturnal blood pressure (BP) and the circadian rhythm of BP were studied. Ambulatory BP and heart rate (HR) were monitored at 30-minute intervals for 24 hours, in 326 normotensive volunteers aged 15-83. The following groups were monitored: young: < 40 yrs, n = 177; middle: 40 yrs < or = - < 60 years, n = 100; old: 60 yrs < or =, n = 49 Firstly, the ratio of nocturnal fall (RONF) of BP (or HR) was calculated as follows: [(average day time BP (or HR) average night time BR (or HR)]/averaged whole day BP (or HR) x 100. Then we calculated 2 measurements: 1. The dipper (RONF of BP (or HR) > or = 10% 2. The non-dipper. (RONF of BP (or HR) < 10%. A cosine fitting technique using the least squares method was employed to find the circadian rhythm of BP and HR. The results of the study showed that the incidence of the non-dipper on systolic BP (SBP) was higher for old subjects than for young subjects. In addition, the nocturnal BP and HR were higher for old subjects than for young subjects. The circadian amplitude of HR was lower in old subjects. The circadian midline estimating statistic of rhythm (MESOR) or SBP increased with age. The circadian acrophase of BP and HR increased with age. CONCLUSION: non-dippers of BP and HR were observed in any age groups. The frequency of BP and HR non-dipper was greater for old subjects than young subjects. This result may suggest the clinical significance of nocturnal BP and HR for the evaluation of hypertensive subjects. PMID- 8207874 TI - [A clinicopathological study of senile dementia of Alzheimer's type (SDAT) and white matter lesions of Binswanger's type]. AB - A clinicopathological study of senile dementia of Alzheimer's type (SDAT) accompanied by the white matter lesions of Binswanger's type was carried out. Fifty-seven patients, who were diagnosed as suffering from SDAT based on clinical and pathological criteria, were classified into two groups based on the white matter lesions of Binswanger's type. Namely, group 1 consisted of the SDAT patients without any subcortical or white matter lesions (30 cases); group 2 consisted of those with white matter lesions of Binswanger's type (11 cases). The other 9 cases included those with vascular lesions and 4 with some of the same pathological changes found in Parkinson's disease. Clinically, group 2 patients showed subcortical symptoms such as urinary incontinence, Parkinsonian gait, being accompanied by hypertension and arrhythmias. Periventricular lucency (CT) were common in group 2. Macroscopically, both groups showed moderately to severe atrophy, and the width of the corpus callosum of group 2 was narrower than that of group 1. There was no difference in cerebral arteriosclerosis between the groups. In microscopic findings, patients in group 2 showed diffuse distribution of cortical changes such as senile plaques as well as Alzheimer's senile plaques as well as Alzheimer's neurofibrillary tangles while those in group 1 showed various types of diffuse or local distribution. Arteriolosclerosis of the white matter were found in both groups. There was no difference in aortic atherosclerosis and/or heart disease. The complication of white matter lesions of Binswanger's type was not a rare finding in SDAT. PMID- 8207875 TI - [Normal ranges of blood urea nitrogen and serum creatinine levels in the community-dwelling elderly subjects aged 70 years or over--correlation between age and renal function]. AB - To estimate normal ranges of blood urea nitrogen (BUN) and serum creatinine (Cr) levels in the aged, we measured BUN and Cr levels in 332 cases of apparent healthy elderly subjects (male, 152; female, 180) aged 70 years or more. We measured the variables also in 315 cases of sex-matched young control subjects (male, 139; female, 176). This study was a part of the Kahoku Longitudinal Aging Study (KLAS) that aims to reveal the comprehensive functions in the aged. We calculated the mean and the standard deviation (SD) in each group, and excluded subjects with values beyond twice the SD-line. We defined the normal range as range within the single SD-line of the remainder. The estimated normal range of BUN was 14-23 mg/dl both in male and female elderly subjects, and that of Cr was 0.9-1.3 mg/dl in male and was 0.7-1.1 mg/dl in female. The mean BUN level in the elderly subjects was significantly higher than that in the control young subjects. The mean Cr level in the elderly subjects was slightly higher than that in the control subjects. Significant positive correlation was found between BUN levels and age in male elderly subjects. Although Cr levels did not correlate with age in elderly subjects, Cr levels divided by body surface area significantly correlated with age. We concluded that the normal range of BUN and Cr levels differed between young and elderly subjects, and that the decline in renal function correlated with age after the seventh decade. PMID- 8207877 TI - [Intra-ventricular pressure gradient and systolic anterior movement of the mitral valve associated with administration of dopamine in a 91-year-old patient]. AB - A 91-year-old woman had decreased systemic blood pressure accompanied by dyspnea and general fatigue after resection of a face tumor (Merkel cell carcinoma). Dopamine was administered to elevate systemic blood pressure, but it did not sufficiently restore the hemodynamic status. Left ventricular apical aneurysm was observed on echocardiogram. Furthermore, SAM (systolic anterior movement of the mitral valve) was observed on M-mode echocardiogram and a pressure gradient of 34.6 mmHg in the midventricular position was confirmed by continuous wave Doppler using the Bernoulli equation. After volume overload and discontinuation of dopamine, SAM completely disappeared and midventricular pressure gradient markedly decreased. Her general condition improved. Because of the narrowed outflow tract, hypercontractile state induced by beta adrenergic stimulation seemed to be one of the important factors for the genesis of SAM and pressure gradient. PMID- 8207876 TI - [Radiation therapy of carcinoma of the esophagus in the aged--its results and problems]. AB - Clinical records of 128 non-selected patients with esophageal cancer treated by radiation were reviewed to investigate reasons why treatment had to be discontinued, relationship between age and survival, and factors influencing prognosis. Radiation therapy was completed in 77 patients but was discontinued in 27 patients. Preoperative radiation was attempted in 24 patients. An overall median survival of 128 patients was 6.4 months, with 8.5 and 3.3 percent surviving 3 and 5 years. Median survivals of incomplete RT, completed Rt and RT + Surgery were 1.3, 7.7 and 11.3 months. By Kaplan-Meier analysis significant difference was observed in survival rate between incomplete RT and the other two groups, but not between RT and RT + surgery. T1 tumor cases with incomplete RT were characterized by a higher C-Score (higher incidence of comorbidity and complications), lower albumin concentration and poor performance status. Median survivals of 60 years, 70 and 80 were 12, 5.4 and 6.2 months, respectively. Performance status and C-score were significantly different between the 60 yr and 80 yr groups. Survival rates were also apparently affected by the size of the primary tumor and metastasis. Thus important factors influencing prognosis were performance status, albumin concentration, and comorbidity and complications, in addition to stage of tumor itself. Although performance status and albumin concentration were considered directly related to tumor stage, old age may have an adverse effect on these factors through increase of comorbidity and complication. The data may be useful for decision making for treatment of esophageal cancer of the aged. PMID- 8207878 TI - [Surgical treatment of subaortic stenosis]. AB - We reviewed 10 cases with subaortic stenosis (SAS) who underwent surgical repairs in our hospital. They were divided into 3 groups. Group I-A included patients with discrete SAS which had been detected before the initial operation. Group I-B included patients with discrete SAS which became apparent following the initial operations. Group II patients included SAS except the discrete type. Surgical treatment of each group was discussed. In group IA, there were no early deaths nor late deaths. There was 1 reoperation due to restenosis. Group IB had 3 cases which included VSD with CoA, Taussig-Bing anomaly, and common atrioventricular canal with VSD. In the Taussig-Bing anomaly case, an arterial switch (Lecompte maneuver) was performed 3 years ago. SAS was successfully relieved with the right ventriculotomy and VSD patch incision. Group II had 3 cases. There were 2 operative deaths and 1 late death. SAS was relieved by, in two cases, Stansel anastomosis with BT shunt and, in the last one, palliative arterial switch operation. It was extremely difficult to detect SAS in group II, when SAS had rapidly progressed following PAB in neonate and early infant. Our present policy is that PAB would be performed if there is no apparent SAS before the initial operation. SAS should be relieved as soon as possible if it is apparent at the postoperative period. Either Stansel anastomosis with BT shunt or palliative arterial switch operation would be the best choice in such a difficult case. PMID- 8207879 TI - [Percutaneous transluminal angioplasty for stenosis of coronary artery bypass grafts: a comparison of arterial grafts versus vein grafts with regard to restenosis and re-do CABG]. AB - Stenoses of ten arterial grafts and thirty-four venous grafts from previous coronary artery bypass grafting (CABG) were treated with percutaneous transluminal angioplasty. In all ten arterial grafts, stenosis occurred at the distal coronary anastomotic site (A-d). In vein grafts, stenosis occurred at the proximal aortic anastomotic site (V-p) in 10, at the graft body (V-b) in 9 and the distal coronary anastomotic site (V-d) in 10 vessels. The initial success rates of angioplasty were 89% (A-d), 100% (V-p), 89% (V-b) and 100% (V-d). The time period between CABG and angioplasty was significantly shorter for A-d (4 +/- 3.8 months) and V-d (8.1 +/- 9.9 months) groups than for V-p (56.9 +/- 35.7 months) or V-b (45.9 +/- 48.6 months) groups. The restenosis rates following angioplasty were 0% (A-d), 50% (V-p), 50% (V-b) and 0% (V-d). Repeat CABG surgery was required for restenosis in 2 patients of group V-p and V-b. Our experience suggests that angioplasty can be performed with a high success rate for stenosis at the distal anastomosis of either arterial or vein grafts after CABG. PMID- 8207880 TI - [Analysis of left ventricular function early after coronary artery bypass grating in patients with left ventricular dysfunction]. AB - We analyzed left ventricular (LV) function early after coronary artery bypass grafting (CABG) in patients with LV dysfunction, whose LV ejection fraction (LVEF) was less than 0.4. 11 patients were divided into two groups: Group-A patients (G-A: n = 6) improved LVEF (post-op LVEF > 0.4) and Group-B patients (G B: n + 5) did not improve LVEF (post-op LVEF < 0.4) one month after CABG. Preoperative status of coronary artery disease, cardiac function, operative procedure, and postoperative cardiac function were compared between two groups. All patient had old myocardial infarction. There were no differences in preoperative LVEF (0.30 +/- 0.06 in G-A and 0.31 +/- 0.06 in G-B), CI, and LVEDP between two groups. LVEDVI (85 +/- 19 in G-A and 159 +/- 50 ml/m2 in G-B) and LVESVI (60 +/- 14 in G-A and 113 +/- 49 ml/m2 in G-B) values were higher in G-B, respectively. Number of grafts was not different between two groups (2.3 in G-A and 2.4 in G-B). Postoperative LVEF value (0.53 +/- 0.07 in G-A and 0.34 +/- 0.04 in G-B) was lower in G-B. Thus, it might be difficult to obtain the recovery of LV function in patients with LV dilatation, early after CABG. PMID- 8207881 TI - [Efficacy of lidocaine cardioplegia for spontaneous resumption of heart beating]. AB - Efficacy of lidocaine for cardiac rhythms after aortic declamping was evaluated retrospectively. Twenty-four patients undergoing coronary artery bypass grafting (CABG) (Group C1) and seven patients undergoing aortic or mitral valve replacement (VR) (Group V1) received crystalloid cardioplegia without lidocaine, while 21 patients undergoing CABG (Group C2) and 19 patients undergoing VR (Group V2) received lidocaine (50 mg/l) added crystalloid cardioplegia. After aortic declamping, there was a significant increase in spontaneous resumption of heart beating in Group C2 (71.4%) and Group V2 (57.9%), as compared with their respective counterparts, Group C1 (4.2%) and Group V1 (0%). Mean attempts of electrical defibrillation were significantly decreased in Group C2 (one time) and Group V2 (1.33 times), while electrical defibrillation was required 1.74 times in Group C1 and 2.71 times in Group V1. The present study suggests that lidocaine cardioplegia increases spontaneous defibrillation and decreases the need of electrical defibrillation. PMID- 8207882 TI - [A device of intercostal thoracotomy for preparing an intercostal muscle flap]. AB - A device of intercostal thoracotomy for preparing an intercostal muscle flap (IMF) is reported. In order to preserve a intercostal muscle (IM) at the level of thoracotomy, a thoracotomy is preformed by incision of lower edge of IM. By this technique, an intercostal thoracotomy can be performed with preservation of an IM. In a case with high risk of bronchopleural fistulas after pulmonary resection, this preserved IM can be easily used for preparing a muscle flap in order to wrap the bronchial stump or the anastomotic site of bronchoplasty. We have used IMF by this technique for 6 cases of lobectomy and 8 cases of bronchoplasty, which have high risk of postoperative bronchopleural fistulas. Of these 14 cases, there have been no postoperative bronchopleural fistulas, including the other complications. By this method of the intercostal thoracotomy with preservation of IM, IMF can be easily prepared without the use of other IMs, even when high risk of bronchopleural fistulas is newly anticipated after pulmonary resection. Therefore, the presented method of the intercostal thoracotomy is recommended for a routine thoracotomy. PMID- 8207883 TI - [Clinical experience of autotransfusion of shed mediastinal blood using a new device]. AB - Autotransfusion of shed mediastinal blood is expected to be adopted as a technique to reduce transfusion thus preventing various complications such as hepatitis, AIDS, and GVHD. We report the usefulness and problems of a new device Solcotrans Plus, which only requires connection to wall suction. This device consists of three parts: suction, reservoir bag, and filter for autoinfusion. After setting the suction and reservoir bag primed with anticoagulant, ACD or heparin, and connecting the unit to a wall suction, we performed autotransfusion of shed blood through the filtration component in ICU after operation. Postoperative hematological and biochemical examinations revealed no complications or adverse effects of autotransfusion. This device is available, simple to handle, and is useful for returning shed blood. We believe that this device will be effective for non-blood open heart surgery or reduction of transfusion. PMID- 8207884 TI - [A case of Cabrol's procedure in which selective cerebral perfusion was necessitated]. AB - A 69-year-old man underwent Cabrol's procedure for annuloaortic ectasia and complicated multiple cerebral infarction. Preoperative CT scan showed atherosclerotic changes from the aortic arch to descending aorta. During extracorporeal circulation, arterial cannulation was made through left subclavian artery to prevent cerebral infarction due to detouched atheroma from the descending aorta. Intraoperatively, the ascending aorta was also atheromatous and ulcerative. In this case, cerebral infarction was most likely due to detouched atheroma from the aortic arch in retrograde blood flow during extracorporeal circulation. To prevent this complication, selective cerebral perfusion during extracorporeal circulation should have been selected. PMID- 8207885 TI - [Long-term results after surgical repair for aged atrial septal defect]. AB - Between 1980 and 1992, 84 patients over 30 years were underwent operative closure of atrial septal defect (ASD). Preoperative complaints and lower cardiac function were more frequent in the older than in the younger, but the clinical symptom of both generation improved significantly after surgery. Only a 67-year-old patient died after surgery due to low cardiac output syndrome. No long-term death occurred. The incidence of atrial fibrillation was increased postoperatively compared with preoperatively. Therefore, we recommend early surgical repair for aged ASD before thirties, if possible. PMID- 8207886 TI - [CT guided percutaneous needle biopsy of mediastinal lymph nodes for staging of primary lung carcinoma]. AB - In cases of primary lung carcinoma, diagnosis of metastatic mediastinal lymph nodes using computed tomography (CT) is usually difficult, and mediastinoscopy is highly invasive for patients. By using CT guided percutaneous needle aspiration technique, we diagnosed the metastasis to mediastinal lymph nodes in three cases of primary lung carcinoma. In this method, percutaneous biopsy was easily performed even in obesed patient, and metastatic lymph nodes were differentiated from large vessels by using enhanced CT to avoid dangerous punctures. Furthermore, biopsy of almost all mediastinal lymph nodes may be feasible by using both anterior and posterior approach. This method seems to be very useful for the diagnosis of the staging of primary lung carcinoma. PMID- 8207887 TI - [A case of emergent surgical salvage for the mitral prosthetic perivalvular leakage diagnosed only by the transesophageal Doppler echocardiography]. AB - A case of the successful emergency surgery for the mitral prosthetic perivalvular leakage (PVL) which was diagnosed only by the transesophageal Doppler echocardiography (TEE) is reported. A 59-year-old male who had been diagnosed MS + TR + severe PH underwent mitral valve replacement with St. Jude medical valve 27 M. On the eighteenth postoperative day hemoglobinuria was noticed suddenly. Subsequently hemolysis and nonoriguric renal failure was aggravated, then we suspected PVL, but heart murmur was not audible or PVL could not been detected by the transthoracic echocardiography (TTE). PVL was detected for the first time by the TEE, then open heart resuture was emergently performed. The site of the PVL was the portion where the anterior mitral annulus adjoined the aortic annulus, that is, adjacent to the right fibrous trigone. This site is the portion which a surgeon should treat very carefully and where the PVL is very difficult to detect by the TTE. In regard to the detection of the PVL in mitral position, the TEE, which has ultrasonically no flow masking by the mitral prosthesis, is the very useful diagnostic means. PMID- 8207888 TI - [A case of hypertrophic obstructive cardiomyopathy (HOCM) complicated by infective endocarditis (IE) and mitral regurgitation (MR)]. AB - The case of a 56-year-old man who underwent mitral valve replacement due to HOCM complicated by IE and MR is reported. Preoperative 2D echocardiographic assessment of the mitral valve revealed systole anterior motion (SAM) and vegetation, and color flow Doppler echocardiographic examination revealed severe mitral regurgitation. The left ventricular out-flow tract gradient decreased from 140 mmHg preoperatively to 60 mmHg postoperatively. Mitral valve replacement should be considered in patients with associated IE and severe MR. PMID- 8207889 TI - [A case report of mitral valve replacement for infective endocarditis in pregnancy]. AB - Infective endocarditis in pregnancy is uncommon. A 37-week pregnant woman presented with infective endocarditis. Echocardiography revealed prominent mitral valve vegetations. The patient underwent cesarean section and a 2,800 g male infant was delivered. In order to prevent embolization, mitral valve replacement was performed 3 days after cesarean section with SJM valve. Both mother and child are doing well now. PMID- 8207890 TI - [Mitral valve aneurysm in a patient with mitral regurgitation: a case report]. AB - A 66-year-old man admitted to our hospital complaining of severe dyspnea. Echocardiography demonstrated severe mitral regurgitation and an abnormal echo at the anterior leaflet of the mitral valve. It was a persistent bulge that protruded toward the left atrium throughout systole and diastole. Left ventriculography also demonstrated the same abnormal shadow of the mitral valve. At the operation, it was seen that two of the chordae tendineae of the anterior leaflet had ruptured and a small aneurysm, approximately 10 mm in length, originated from the lateral part of the leaflet. The aneurysm protruded into the left atrium and had neither rupture nor perforation. Because the aneurysm of the mitral valve was too large to resect and repair the valve, it was replaced with St. Jude Medical Valve (29 M). IABP was needed at the weaning from cardiopulmonary bypass, but he recovered gradually well afterwards. The excised anterior leaflet showed myxomatous degeneration, but had no vegetation and rheumatic change. Microscopic examination of the valve aslo revealed myxomatous degeneration and no signs of the inflammation. PMID- 8207891 TI - [Transcatheter embolization of aorto-pulmonary collateral arteries in cyanotic congenital heart disease]. AB - Transcatheter embolization (TE) using steel coils was performed on three patients with aorto-pulmonary collateral arteries (APCAs). Case #1: In a 13-year-old boy who had undergone corrective surgery for pulmonary atresia with ventricular septal defect (PA with VSD), one APCA was embolized by the TE technique. This resulted in a remarkable improvement in postoperative pulmonary congestion. Case #2: A 13-year-old boy who had previously undergone procedures to correct tetralogy of Fallot (TOF), underwent TE for two APCAs prior to subsequent surgery before for pulmonary stenosis. The procedure abandoned one APCA because of the long narrow origin of the vessel. For the other APCA, TE was unsuccessfully performed due to the displacement of a coil into the peripheral pulmonary artery. Case #3: An 8-year-old girl with PA with VSD underwent TE for three APCAs before corrective surgery. One APCA arising from the abdominal aorta was occluded successfully. The other two were considered too small at the orifice for TE, and were ligated surgically before corrective surgery. TE is a safe and effective method for suitable cases of APCAs. However, caution should be exercised to prevent complications. The selection of appropriate coils and catheters is also important. PMID- 8207892 TI - [A female case of adenocarcinoma of the lung producing human chorionic gonadotropin]. AB - A 72-year-old female was admitted with complaints of cough and sputum. The chest X-ray film revealed a solitary round mass and pleural effusion in the left lower lung field. Laboratory tests demonstrated elevated levels of serum HCG and beta HCG. Left lower lobectomy with parietal pleurectomy was performed under the diagnosis of primary lung cancer with malignant effusion. The serum HCG level decreased after the operation. Histologically, the tumor was diagnosed as moderately differentiated papillo-tubular adenocarcinoma of the lung. In the HCG staining using an immunohistochemical method, the tumor cells showed a positive reaction. Thus, this tumor was definitively diagnosed to be HCG-producing adenocarcinoma of the lung. PMID- 8207893 TI - [A case of lung cancer with axillary nodal involvement]. AB - A 57-year-old man with lung cancer was reported. Primary tumor was located at left S1+2, and directly invaded to chest wall (from 1st. rib to 4th rib). Hypercalcemia and delirium were observed. Whole body examination showed that no distant metastasis except for nodal swelling of left axillary region. Left upper lobectomy combined with chest wall resection was performed. Hilar, mediastinal and axillary nodes were also dissected. Histological examination revealed that nodal involvement was not present at neither hilar or mediastinal region, but was present in axillary node. It was thought that lymphatic extension had occurred from trough chest wall to axillary nodes but not through mediastinal rout. So systematic dissection of locally invaded region as well as hilar and mediastinal region was recommended in each cases. PMID- 8207894 TI - [A case of mediastinal malignant lymphoma; 16 years follow up after surgery]. AB - A 32-year-old female was admitted to our hospital on September 1976 because of left mediastinal mass shadows on chest roentgenogram. Needle biopsy studies provided no definitive diagnosis, and exploratory operation was carried out through left postero-lateral thoracotomy. Two large masses were seen in the mediastinum and five small tumors were seen on the diaphragm. All of these masses were removed. Histopathological examination of the tumors indicated non-Hodgkin's lymphoma, diffuse small cell type. Radiation therapy was carried out postoperatively, but chemotherapy could not continue because of side effect. Eight years after surgical therapy, recurrence was seen at left parietal pleura, ten years at peritoneum, twelve years at left parietal pleura, thirteen years at upper mediastinal lymph node, 16 years at post-peritoneal space. These tumors disappeared after radiation therapy. She is doing well seventeen years after the surgery. PMID- 8207895 TI - [A case of unusual shaped pulmonary arteriovenous fistula]. AB - Autopsy findings of pulmonary arteriovenous fistula (PAVF) was initially described by Churton in 1897. Since then, several hundreds of cases have been reported in Europe and the United States. In Japan, there has recently been an increase in case reports of PAVF. PAVF seems to be no longer a rare disorder in Japan. Several morphological classifications of PAVF have been reported. One of these classifies PAVF into 1) solitary types 2) multiple types and 3) diffuse telangiectasia. Another, for example, classifies the disorder into the following 3 types: 1) multiple telangiectasia 2) pulmonary arterial aneurysm and 3) pulmonary artery-left atrial communications. Many other classifications have been proposed. In the solitary type (PA aneurysmal type), fistulas are located at the relatively large, central vessels. Here we report a case of PAVF which presented not as a solitary aneurysm but rather as a distended and tortuous anomalous vessel. PMID- 8207896 TI - [A case of catamenial pneumothorax associated with diaphragmatic endometriosis]. AB - A case of catamenial pneumothorax associated with diaphragmatic endometriosis was reported. A 43-year-old woman had 4 times-recurrent pneumothorax on right side for recent 5 months. Each onset was related to the beginning of menses. Right thoracotomy revealed the presence of multiple darkly-pigmented spots and several pinhole like perforations in the central tendon of diaphragm. The area showing these lesions were considered to be the focal region, and this part of diaphragm was excised. Histology showed the stromal endometriosis surrounded by hemosiderin pigment deposits. The patient has been asymptomatic for 4 years after operation. Our case may give support to Maurer's hypothesis. Surgeons should be aware of the importance of carefully inspecting the diaphragm during operation. PMID- 8207897 TI - [Pulmonary sequestration diagnosed by combined computed tomography without contrast enhancement and magnetic resonance imaging: a case report]. AB - A 71-year-old woman with pulmonary sequestration had iodine hypersensitivity. Diagnosis was made using computed tomography without contrast enhancement and magnetic resonance imaging. An anomalous artery arising from the descending thoracic aorta was clearly defined. Thus the diagnosis of pulmonary sequestration was confirmed before successful operation without angiography. This diagnostic procedure is safe, noninvasive and useful to detect the anomalous artery, especially in the patient with iodine hypersensitivity. PMID- 8207898 TI - [The surgical correction of iatrogenic damage to and cicatricial stricture of the extrahepatic bile ducts]. AB - In treatment of 86 patients with a iatrogenic injury, or cicatricial stricture of the extrahepatic bile ducts, the Prader-Smith, Saypole-Kurian transhepatic drainage of hepatico-digestive anastomosis and that with the use of the method suggested by the authors have been used. The technique for performance of the operations is described, the special instruments are offered. After the operation, only one female patient has developed a subphrenic abscess. PMID- 8207899 TI - [The use of Kapromed A and Kaproiod sutures in surgery of the extrahepatic bile ducts]. AB - The experimental substantiation and clinical approbation of the absorbable antimicrobial threads "Capromed A" and "Caproiod" in the surgery of the extrahepatic bile-ducts were carried out. The complications caused by the use of suture material were not revealed. A high effectiveness of the "Caproiod" thread in the emergency surgery of the extrahepatic bile ducts was noted. PMID- 8207900 TI - [The use of laser radiation for correcting cholesterol metabolic disorders in gallstones]. AB - The authors have demonstrated in the experiment that under the influence of irradiation of the liver by means of a semiconductor laser with a wavelength of 890 nm, pronounced activation of its microsomal system occurs. The data obtained have become a basis for the development and introduction in the clinic in 96 patients of a technique of laser correction of hypercholesterolemia. A good therapeutic effect has been noted in all the patients. PMID- 8207901 TI - [Simultaneous operations in surgery of the biliary tract]. AB - The experience with simultaneous performance of the operations on the bile ducts and other organs in 802 patients, including 109 who underwent simultaneous operations on 2 or several organs for pathogenetically unrelated diseases (lethality--1.9%), 662--combined interventions on the anatomically and functionally connected organs for main disease and its complications (lethality 29%), is summarized. Simultaneous performance of the operations ensures the effective and radical surgical treatment. PMID- 8207902 TI - [The placing of a distal splenorenal anastomosis in liver cirrhosis patients]. AB - The results of treatment of 79 patients with hepatic cirrhosis and different manifestations of portal hypertension, who had a distal splenorenal anastomosis been created, were studied. The features of hepatic failure after the operation were noted in 37 (46.8%) patients. Of them; 18 died. Within a five-year period, 56.4% of the patients are alive. The lifetime was the shortest in patients with ascites which developed after bleeding from the esophageal and gastric varices. The authors stress the importance of the development of criteria for evaluation of risk factors and efficacy of the operation. PMID- 8207903 TI - [The combined prevention of postoperative suppurative-septic complications in patients with a fistula of the extrahepatic bile ducts]. AB - The authors have suggested a complex scheme for immunoprophylaxis of purulent septic complications in patients with a fistula of the bile ducts, including study of the immune status, choice of the adequate immune correctors and antibiotics which act effectively on the pathogenic microflora, at individually adjusted dosages, performance of pre- and postoperative immunocorrection and immunotropic antibiotic therapy. PMID- 8207904 TI - [The stress reaction in cholecystectomy and the possibilities for its limitation]. AB - In 82 patients, the biochemical indices of the operative stress-reaction during performance of cholecystectomy were studied. The possibility of inclusion into the existing schemes of preoperative preparation and postoperative management of the patients of a complex of means with central and peripheric stress-limiting action to decrease the pronouncement and duration of operative stress was investigated. PMID- 8207905 TI - [Plasmapheresis and immunocorrective therapy in the combined treatment of patients with pancreatic necrosis]. AB - The results of the use of plasmapheresis and immunocorrective therapy in the complex of treatment of 46 patients with pancreonecrosis have been analysed. It is shown that a degree of endogenous intoxication correlates with severity of the state of a patient, suppression of the factors of cellular immunity which normalize under the influence of plasmapheresis and immunocorrective therapy. Stable and progressive suppression of the factors of cellular immunity and sharp increase in the level of alpha-fetoprotein are the prognostically unfavourable signs which are indicative of suppression of the immune response. PMID- 8207906 TI - [The possibilities for correcting the dysbacteriosis occurring in the prolonged external diversion of bile]. AB - The possibility to correct postoperative dysbacteriosis in patients, who had their operation been completed with external drainage of the common bile duct, was studied. Resulting from the use of Normaze preparation in combination with Bifidumbacterin adsorbed on SKN carbon sorbent, the composition of intestinal microflora has restored, bile structure improved. PMID- 8207907 TI - [The morphofunctional state of the stomach depending on the method of resection]. PMID- 8207908 TI - [The preparation of the duodenum in different methods of stump closure and their classification]. AB - The experience with surgical treatment of 222 patients with duodenal ulcer disease has been summarized. A method for surgical preparation of the duodenum with the optimal use of plastic properties of its wall is suggested. A classification of the methods for duodenal stump closure is presented. PMID- 8207909 TI - [The prognosis of liver failure in patients with liver cirrhosis under surgical treatment for portal hypertension]. AB - On the basis of studying the intraoperative biopsy specimens in 44 patients with hepatic cirrhosis and portal hypertension syndrome, who had a distal splenorenal anastomosis been created, the authors have distinguished three types of morphological changes--A, B, C. A significant dependence between the type of cirrhosis and pronouncement of hepatic failure after the operation and life-time of a patient after the operation as well has been established. Type C has the greatest risk, type B requires differential approach, type A is prognostically favourable concerning both the outcome of the operation and life-time of a patient. PMID- 8207910 TI - [The means of eliminating the intoxication in suppurative peritonitis]. AB - On the basis of experience with treatment of 351 patient with purulent peritonitis, the authors have drawn a conclusion about the expedience of cascade increasing the intensity of detoxication therapy depending on pronouncement of intoxication. Resulting from complex use of electrostimulation of the intestine, unloading stoma, hemosorption, ultraviolet blood irradiation, intra-aortal administration of drugs, the mortality in patients with severe intoxication decreased by 7.5%. PMID- 8207911 TI - [The diagnosis and treatment of a closed abdominal injury]]. AB - The experience with diagnosis and treatment of 216 sufferers with closed injury to the abdomen, including 186 who were operated on, has been summarized. The main methods for diagnosis of closed abdominal injury are laparoscopy and laparocentesis, the operation of choice--laparotomy. PMID- 8207912 TI - [The validation of the choice of individual procedure in the drainage of a lung abscess]. AB - Examined were 70 patients with an uncomplicated pulmonary abscess. It was established that a giant abscess had developed against the background of chronic bronchitis with valvular mechanism of impairement in bronchial patency and increased pressure in the cavity of an abscess. Therefore, the performance of decompression by means of transthoracic drainage was required. In patients with a small abscess, bronchitis was secondary, and bronchial patency was restored during abscessoscopy by means of sanation of the cavity and transthoracic administration of antibiotics. Patients with "dry" cavity didn't require the specialised aid. The conservative treatment was effective in 64 (91.4%) patients, 1 (1.6%) died; operated on were 5 (7%), 1 (20%) died. Total lethality was 2.9%. PMID- 8207914 TI - [The use of emulsified fatty substances for the treatment of acute peritonitis and adhesions of the abdominal cavity]. AB - In the experiment on 49 animals, including 29 with modelled acute peritonitis the anticommissural effect of emulsified fatty substances was studied. In introduction into the abdominal cavity, the substances studied had no toxic effect, caused no embolism, abscesses and adhesions. The method was successfully used in the clinic in 25 patients. PMID- 8207913 TI - [External and internal drainage in the surgery of inflammatory diseases of the gallbladder and extrahepatic bile ducts]. AB - Of the 586 patients operated on for acute and chronic calculous cholecystitis, postcholecystectomy syndrome, 304 (51.8%) had external or internal drainage of the bile ducts been performed. External drainage was employed in 251, transduodenal papillosphincterotomy--in 87 patients, biliodigestive anastomosis was created in 52. In 93 patients, the external and internal drainage were combined. Indications for performance and separate methods for external and internal drainage of the bile ducts were defined. The postoperative lethality was 1.3%. PMID- 8207915 TI - [Debatable problems in surgery on the extrahepatic bile ducts]. PMID- 8207916 TI - [The use of low temperatures in treating acute pancreatitis and the outlook for the use of the method]. PMID- 8207917 TI - [The indications for the surgical treatment of an uncomplicated duodenal ulcer]. PMID- 8207918 TI - [A method for correcting duodenogastric reflux]. PMID- 8207919 TI - [A method of transduodenal sphincteroplasty]. PMID- 8207920 TI - [Hemangioendothelioma of the gastrocolic ligament simulating a pancreatic cyst]. PMID- 8207921 TI - [The surgical treatment of calculous pancreatitis]. PMID- 8207922 TI - [The healing of a duodenal ulcer with the elimination of compression of the vagus nerve in the mediastinum]. PMID- 8207923 TI - [A Billroth-II gastric resection in reverse turning of the large intestine]. PMID- 8207924 TI - [Combined volvulus and cancer of the sigmoid intestine]. PMID- 8207925 TI - [A favorable long-term result in the treatment of rectal cancer following multiple electrocoagulation of the tumor]. PMID- 8207926 TI - [Complete transverse rupture of the diaphragm with displacement of the liver into the right pleural cavity]. PMID- 8207927 TI - [The use of the YAG laser in removing a broncholith from the main bronchus]. PMID- 8207928 TI - [A rational procedure for the treatment of patients with chronic calculous cholecystitis complicated by choledocholithiasis]. AB - The results of surgical treatment of 156 patients with chronic calculous cholecystitis complicated by choledocholithiasis have been analysed. In 62 patients, cholecystectomy in combination with choledocholithotomy was performed. Ninety four patients underwent additional drainage operations on the terminal common bile duct. Endoscopic papillosphincterotomy was performed in 90% of cases, other drainage interventions (choledochoduodenostomy and transduodenal papillosphincterotomy)--in 10%. PMID- 8207929 TI - Hypochlorite adulteration of urine causing decreased concentration of delta 9-THC COOH by GC/MS. AB - Marijuana is confirmed and quantitated in urine as 11-nor-delta 9-THC-9-COOH by GC/MS in the selected ion monitoring mode after extraction from urine. The addition of varying amounts of household bleach causes significant decreases in the quantitated amounts of tetrahydrocannabinol (THC). Urine samples containing various known amounts of THC (25-219 ng/mL) were spiked with increasing amounts of household bleach (0-64 microL/mL of urine). The samples were extracted using a solid-phase extraction procedure, derivatized, and analyzed by GC/MS. The area counts for the deuterated internal standard versus the native drug, as well as the quantitation for the various spiked samples, were compared with those of the non-adulterated samples. The results demonstrated that there was an inverse relationship between the amount of bleach used and the amount of THC recovered. The area counts for both the deuterated and native THC decreased as the amount of bleach increased. There appeared to be a consistent decrease in the ratio of native to deuterated THC, suggesting that the bleach affected the native drug more than the deuterated compound. The same decrease in THC concentrations were noted when the samples were assayed by an RIA methodology (Roche Abuscreen) as well as by an FPIA assay (Abbott TDx). PMID- 8207930 TI - Optimization of storage conditions for cocaine and benzoylecgonine in urine: a review. AB - The maximum stability conditions for cocaine and its metabolite benzoylecgonine (BE) in urine were analyzed. Suggestions were presented after careful review of many studies and personal communications concerning cocaine and BE stability in urine. The optimal storage conditions for urine specimens with cocaine and BE were determined to be at -15 degrees C and a pH of 5.0. Ascorbic acid was found to be a favorable agent to attain this acidic pH. Unsilanized glass was determined to be a favorable container material. Storage in darkness was also supported. Storage of urine specimens under these conditions was believed to prevent degradation of cocaine and benzoylecgonine for at least 110 days. PMID- 8207931 TI - Method comparison of EMIT 700 and EMIT II with RIA for drug screening. AB - The EMIT 700 and EMIT II assays for marijuana, cocaine, opiates, barbiturates, and phencyclidine, as performed on a Hitachi 717 Analyzer, were compared with Roche Abuscreen RIA tests for high-volume drug abuse screening. The EMIT II kits offer some advantages over the EMIT 700 kits for testing large work loads. The EMIT II marijuana test in particular exhibits a calibration curve that promises improved ability to separate negative from positive samples due to the increased absorbance rate separation between the negative and cutoff calibrators. Both EMIT formulations are preferable in terms of speed and ease of analysis in comparison with our laboratory's current RIA procedures. Over 50,000 urine samples were screened by EMIT 700 and RIA and by EMIT II and RIA. The performance of both EMIT assays was approximately equivalent to RIA in terms of their ability to detect urine samples that confirmed positive for cocaine and opiates. Both EMIT assays detected approximately 90% of the urine samples screened positive by RIA and confirmed positive for marijuana. Both EMIT assays performed better than RIA in detecting confirmed-positive barbiturate samples. PMID- 8207932 TI - Determination of SCH 39304 by megabore capillary gas-liquid chromatography. AB - A gas-liquid chromatographic procedure for determination of SCH 39304 at low nanogram concentrations in serum, cerebrospinal fluid, and urine is presented. The methodology combines a high selectivity and sensitivity nitrogen-specific detector, a gas chromatograph equipped with a capillary "megabore" column, and an internal standard that is very similar in chemical structure to the drug being assayed. This method is suitable for both pharmacokinetic studies as well as for monitoring drug levels in patients receiving SCH 39304 for antifungal treatment. PMID- 8207933 TI - A report of a suicide involving digoxin and doxepin. AB - In this report we give details on an overdose fatality involving both digoxin and doxepin. There have been numerous reported fatalities, both accidental and suicidal, involving digoxin and many more reports of fatalities involving doxepin. We believe that this is the first time a fatality from this drug combination has been reported in the literature. PMID- 8207934 TI - The origin and significance of ecgonine methyl ester in blood samples. PMID- 8207935 TI - Considering measurement variability when performing retrograde extrapolation of breath alcohol results. PMID- 8207936 TI - Selection of an appropriate initial test cutoff concentration for workplace drug urinalysis--Cannabis example. AB - Apparent analyte concentration (equivalent of 11-nor-delta 9-tetrahydrocannabinol 9-carboxylic acid [9-THC-COOH]) obtained by radioimmunoassay (RIA) for cannabinoids using reagents manufactured at four different periods (from the same manufacturer) and specific 9-THC-COOH concentration as determined by GC/MS are examined for the significance of their correlation. The resulting regression equations are then used to estimate the apparent RIA analyte concentrations of reagents manufactured at different time periods that are equivalent to a specific 9-THC-COOH concentration. Correlation coefficients of the regression analysis improve from approximately 0.4 to 0.7 in parallel with the increasing reagent specificity. The apparent RIA analyte concentrations that correspond to 15 ng/mL 9-THC-COOH decrease from about 110 to 50 ng/mL again in parallel with the increasing reagent specificity. These findings empirically demonstrate that reagent specificity is the determining factor of the resulting apparent RIA analyte concentration when testing samples that contain 9-THC-COOH and other metabolites (derived from marijuana exposure). Thus, if the 9-THC-COOH concentration as determined by GC/MS is of primary concern, the initial test cutoff concentration should be adjusted in accordance with the specificity of the reagent used. PMID- 8207937 TI - Determination of S-benzyl-N-acetyl-L-cysteine by gas chromatography/mass spectrometry as a new marker of toluene exposure. AB - We investigated by gas chromatography/mass spectrometry if S-benzyl-N-acetyl-L cysteine (SBAC) is excreted into the urine of six printing workers and 20 sniffers after exposure to toluene. SBAC was extracted from 10 mL urine with chloroform and back extracted into 1M sodium bicarbonate. After acidfying, the sample was reextracted with ethyl acetate. The SBAC in urine was also measured by selected ion monitoring methods, using deuterium-labeled SBAC as an internal standard. An excellent linearity was obtained from 0.01 to 3.0 mg/L (r = 0.998). Urinary concentrations of SBAC were determined quantitatively in all samples from sniffers and printing workers (n = 26, 0.02-43.29 mg/L) but were not determined in the urine of persons not exposed to toluene (n = 40). The results of this experiment indicate that SBAC is excreted as a minor metabolite of toluene in human urine. The analysis of urinary SBAC is a useful tool in identifying toluene exposure. PMID- 8207938 TI - Electron-capture gas chromatographic determination of cyanide, iodide, nitrite, sulfide, and thiocyanate anions by phase-transfer-catalyzed derivatization with pentafluorobenzyl bromide. AB - A sensitive gas chromatographic method has been established for the simultaneous determination of biologically active inorganic anions, including cyanide, iodide, nitrite, sulfide, and thiocyanate anions as their volatile organic derivatives. The method is based on the formation of ion pairs from the anions and a complex cryptand and on the resulting neutral ion-pair partition to an organic phase for derivatization with pentafluorobenzyl bromide. Several parameters affecting the partition and derivatization of the anions were investigated. Individual and simultaneous determination of the anions can be achieved at sub-nmol levels with an electron-capture detector. Partial application of the method for the analysis of cyanide, nitrite, and thiocyanate in real samples proved satisfactory. PMID- 8207939 TI - Determination of albendazole metabolites in plasma by HPLC. AB - Albendazole is an antihelminthic agent belonging to the benzimidazole class and has been used successfully in the treatment of neurocysticercosis. We report here a method for the determination of the two major albendazole metabolites in plasma, albendazole sulfone and albendazole sulfoxide. The method consists of drug extraction from 500 microL of plasma previously acidified with chloroform isopropanol (9:1, v/v) and extract purification with n-hexane immediately before chromatographic analysis. Separation of drugs and of the internal standard (mebendazole) was performed on an RP-18 column using acetonitrile-0.25N sodium acetate buffer (3:7, v/v), pH 5.0, as the mobile phase and using detection at 290 nm. PMID- 8207940 TI - Analysis of the cyanogenic glycoside linamarin in urine by isotachophoresis. AB - A separation system based on isotachophoresis is described for the cyanogenic glycoside linamarin in aqueous solution and in human urine. Isotachophoresis is a migration of a substance in an electric field, which is applied to a system of electrolytes of specific design. Detection is carried out by monitoring conductivity changes. However, for linamarin in urine, a preseparation procedure was necessary because of the high amount of electrolytes. This was performed by affinity chromatography on a silica sorbent column, with cyclohexyl as the functional group by which linamarin was retained. After elution from the column by methanol, a separation and quantitation of linamarin was possible by means of isotachophoresis. The method allowed determinations of urinary linamarin exceeding 100 microM, with a coefficient of variation of 13% at 500 microM. PMID- 8207941 TI - Immunoassay detection of drugs in racing horses: detection of ethacrynic acid and bumetanide in equine urine by ELISA. AB - We have raised antibodies and developed one-step enzyme-linked immunosorbent assays (ELISA) for the diuretics ethacrynic acid and bumetanide as part of a panel of pre- and post-race tests for high potency drugs in racing horses. These ELISA tests are rapid (completed within one hour), sensitive, and can be read by eye. The ELISA detects ethacrynic acid at a drug concentration for half-maximal inhibition (I-50) of about 2.5 ng/mL for the parent drug. After dosing horses intravenously with 5 mg ethacrynic acid per horse, the parent drug or its metabolites are detectable in urine for at least 8 hours. The bumetanide ELISA has an I-50 for the parent drug of about 2.0 ng/mL and will detect bumetanide or its metabolites for about 8 hours in urine after intravenous administration of a 1.7-mg dose per horse. Both antibodies are relatively specific for each drug and do not cross-react with other commonly used diuretics or other acidic compounds often found in post-race equine urine samples. Ethacrynic acid and bumetanide are potent diuretics suspected of being illegally substituted for furosemide in certain racing jurisdictions. Development of these rapid, sensitive, and simple tests for these agents will allow more effective pre- and post-race control of the use of these agents in racing horses. Both tests have recently uncovered several "positives" for these medications in a midwestern racing jurisdiction. PMID- 8207942 TI - A mass transport model of olfaction. AB - A theoretical model of olfaction involving all the major mechanisms in the mass transport of odorant molecules from inspired air to the olfactory receptors is developed. The mechanisms included are: (i) convective bulk flow of odorant molecules to the olfactory region of the nasal cavity by inhaled air, (ii) lateral transport of odorant molecules from the flowing gas stream in the olfactory region onto the olfactory mucus surface, (iii) sorption of odorant molecules into the mucus at the air-mucus interface, (iv) diffusion of odorant molecules through the mucus layer, and (v) interaction of odorant molecules with the olfactory receptor cells. The model is solved to yield the olfactory response as a function of various physical variables such as the inspiratory flow rate, the mass transfer coefficient, the initial concentration of odorant molecules in the inhaled air, the length of the olfactory mucosa, the thickness of the olfactory mucosa, and the air-mucus partitioning (or solubility in the mucus) of odorant molecules. It was determined that the flow rate of the odorant carrier gas, length of the olfactory mucus surface, and the solubility of odorant molecules in the olfactory mucus should play important roles in determining the odor intensity for these odorants. The model predicts that, given adequate mucus surface for sorption, increase in the flow rate results in an increase in perceived odor intensity for the readily sorbed or highly soluble odorants (such as carvone) and a decrease in odor intensity for the poorly sorbed or insoluble odorants (such as octane). With a substantial decrease in the mucus surface for sorption, increase in the flow rate results in a decrease in perceived odor intensity for all odorants. The theoretical results show good agreement with various experimental data obtained from both psychophysical and electrophysiological studies of olfaction using animals and human subjects. PMID- 8207943 TI - A re-evaluation of the properties of the three-compartment model of intestinal weak-electrolyte absorption. AB - The three-compartment model for intestinal weak-electrolyte transport provides an equation which predicts the flux ratio (the ratio of the forward and reverse fluxes of weak electrolyte across the intestine) from the dissociation constant, given that coefficients in the equation are specified. Using the equation to evaluate the coefficients from flux ratio and dissociation constant data fails to provide a unique set of values for the coefficients, although it does provide four dissimilar but related sets of values. Differentiation to determine the position and size of the maximum flux ratio provides a relationship between the model coefficients which shows why it is that four sets of coefficients can be used in the equation when it is applied to experimental data. Coefficient sets are derived for all available flux ratio data in the literature. These always contain a variant which requires the intermediate compartment to be more acid than the end compartment. Further specification of the flux ratio equation either by combining data from different physiological circumstances or by adding voltage terms, reduces the four possible coefficient sets to a single set, again requiring the intermediate compartment to be more acid than the end compartment. Estimates of the intermediate-compartment pH agree well with electrode estimates of mucosal surface pH. The present re-evaluation of the three-compartment model resolves an apparent contradiction between experimental and previous theoretical results which indicated a more alkaline intermediate compartment. Instead of contradicting experimental findings, results from the modelling process confirm that the "acid microclimate" version of the model is the better representation of the system that causes asymmetry in weak electrolyte flows across the small intestine. PMID- 8207944 TI - Analysis on the distribution of bases in 1487 human protein coding sequences. AB - The occurrence frequencies of bases A, C, G and T, denoted by a, c, g and t, respectively, in 1487 human protein coding sequences have been calculated and analyzed. The analysis has been performed by a diagrammatic method presented recently, in which each coding sequence is represented by a point in 3-D space. The distribution of points gives the observer an overall and intuitive picture of the base frequencies. The distance between a point and the origin of the co ordinate, which corresponds to the case of a = c = g = t = 1/4, is called the radical distance. The radical distribution of 1487 points in 3-D space has been found to be normal, with the center basically coinciding with the origin of the co-ordinate. We have found that among 1487 coding sequences, an empirical rule a2 + c2 + g2 + t2 < 1/3 holds for 1486 sequences. The only sequence in which the above rule does not hold is the one coding for the human parathymosin protein. The composition of amino acids and the structural class of this protein has been studied in some detail. PMID- 8207945 TI - Modulation of molecular friction in actomyosin complex by an external electric field. PMID- 8207946 TI - An algorithm combining DNA and protein alignment. AB - An algorithm is presented that aligns two DNA sequences minimizing the overall amount of evolution that the associated proteins have experienced. It is generalized to minimizing a weighted average of protein and DNA evolution. PMID- 8207947 TI - Anesthesia and the Meyer-Overton rule. I. Potencies and perturbations. AB - The Meyer-Overton rule is used extensively in the analysis of general anesthesia, but there is no satisfactory explanation of its origins. In this article we explore its physical content and show that it is not possible to explain this rule by using anesthetic potencies alone: we must consider also the perturbations at anesthetic sites. We then show that, under certain conditions, the Meyer Overton rule can be used as a "perturbation gauge." The findings contradict the common belief that the rule provides little information about interactions of anesthetic molecules with the membrane constituents of the anesthetic site. PMID- 8207948 TI - Anesthesia and the Meyer-Overton rule. II. A solution theory view of anesthesia and perturbations. AB - Solution theory arguments play a significant role in the analysis of general anesthesia. However, the results are of limited value, due to the complexity of the systems to which these arguments are applied. This article suggests that we can advance our understanding of anesthesia by the analysis of a solution of hard spheres as an "ideal anesthetic medium." We obtain a precise definition of perturbation, which links together its structural and thermodynamical aspects in an accurate theory. It follows that this link applies to virtually all material systems, including the complex biological systems where anesthesia occurs. The derived relations: (i) explain the unique role of helium in hyperbaria; (ii) suggest how to establish a hierarchy of importance among possible causes of anesthesia; (iii) indicate the role of the Meyer-Overton rule in analyzing structural models of anesthesia; and (iv) depict the physical meaning of correlations, commonly used in anesthetic work, and show why they are more accurate than the Meyer-Overton rule. PMID- 8207949 TI - The necessary and sufficient conditions of density-dependent evolutionary stable strategy (DDESS) in the two-phenotype model. AB - In this paper, we discuss the stability conditions of both the density-dependent pure and mixed strategy models of a polymorphic haploid population with only two pure strategies. Our results show that for the definition of density dependent evolutionary stable strategy DDESS and its stability. Cressman's frequency conditions are necessary and sufficient, and Cressman's density condition is not required. PMID- 8207950 TI - Navigating a set of discrete regions in body position space. AB - This paper defines a mathematical object that expresses physiological aspects of motor control, besides physical aspects. Based on observations in human development and rehabilitation, this paper lays a foundation for unifying discrete with continuous aspects of motor control. Discreteness in motor control arises from the fact that movements are planned by the organism, based on movement limits set by the organism, the task, and the environment, rather than following simply from physical laws. This paper defines two relations, an ordering and a contiguity relation, between discrete regions of joint space crossed with physical space, to make a d-space. Within the d-space, a particular body and physical position is represented by a completely ordered set, a coincidence. A trajectory through a continuous space is represented by a coincidence sequence. Examples are drawn mostly from human locomotion, with particular interest in balance. Only in certain regions of body and physical position space can a body maintain balance, for example, a standing human. Slow steps proceed from one balanced region to another. A poset (partially ordered set) of sets of steps and its relationship to a person's balance regions can be used in the study of development or rehabilitation. PMID- 8207951 TI - Cell density-sensing in Dictyostelium by means of the accumulation rate, diffusion coefficient and activity threshold of a protein secreted by starved cells. AB - The simple eukaryote Dictyostelium discoideum grows as an amoeba on leaf and soil surfaces. When starved, the amoebae aggregate and differentiate. The amoebae can also be induced to differentiate as isolated cells submerged in buffer, if the buffer contains a sufficiently high concentration of a protein (CMF) secreted by starved cells. CMF is also necessary for aggregation and differentiation on surfaces. This indicated that CMF has either an autocrine function or is part of a density-sensing system. To distinguish between these two possible functions, we first examined the rate at which CMF is accumulated and the activity threshold of cells for CMF, since both parameters will affect whether a cell can provide enough CMF to self-stimulate. We find that CMF potentiates its own accumulation, and that otherwise the accumulation rate and activity threshold are affected very little by a variety of physiological conditions. We then use diffusion calculations to show that even after many hours of continuous secretion, the CMF concentration adjacent to an isolated starved cell on a leaf or soil surface will be too low to allow differentiation, whereas an extracellular concentration of CMF sufficiently high to allow differentiation will occur when starved cells are at high densities. We find a close match between the predicted and experimentally observed density necessary for differentiation. The theoretical and observed behavior of cells at different cell densities suggests that due to its accumulation rate, diffusion coefficient, and activation threshold, CMF can function as part of a cell density-sensing system which allows Dictyostelium cells in the wild to co-ordinate their development. PMID- 8207952 TI - Reverse interpretation: a hypothetical selection mechanism for adaptive mutagenesis based on autoregulated mRNA stability. AB - The problem of adaptive mutagenesis is examined under the assumption that selection occurs through the interaction of cognate mRNA and protein molecules, a phenomenon that has been considered to lead to differential mRNA decay (Kyrpides & Ouzounis, 1993, J. theor. Biol. 163, 373-392). Based on the stereochemical hypothesis, we speculate that the origin of this process relies on an extended form of molecular interactions. This mechanism, termed reverse interpretation, predicts the selective amplification of successful molecular forms with the capability of their immortalization through reverse transcription, in a manner that resembles, but is not equivalent to, reverse translation. Finally, we argue that the proposed mechanism conforms with the Darwinian view of evolutionary change, if variability is considered to be a property of molecular and not cellular populations. PMID- 8207953 TI - Sequential approach for describing channel opening and desensitization. AB - A formula describing the time-course of activation and desensitization of nicotinic-like acetylcholine channels is developed. The method used to arrive at this simplified formula is based on a sequential approach. Based upon this approximated and simple formula, analytical expressions for various specific experimental aspects are derived. These expressions together with the corresponding experiments provide a method to evaluate in a sequential manner the various rate constants involved. PMID- 8207954 TI - On the origin of the periodicity of three in protein coding DNA sequences. PMID- 8207955 TI - Polynuclear aluminium and acute aluminium toxicity in the fish. PMID- 8207956 TI - Design of trials for antibody treatment of tumour. AB - Our discussion is summarized in Fig. 1. Cytotoxic drugs are shown with the classical sigmoid relationship of response to log dose, with a parallel increase in toxicity which suits the Phase I approach. With antibody it is doubtful that clinical tumour ever responds to single doses with an asymptote of 100% ablation, so arbitrarily lower asymptotes have been used, higher for immunotoxins than for antibodies (n). The response curves have been made sigmoid simply by selecting, among the infinity of mathematical functions, two hypothetical functions of dose which yield sigmoid transformations of the data. After superimposing on the graphs the occurrence of toxicity, one discerns with antibodies (n) only a threshold dose, above which any toxicity will be highly dependent on the extent of encounter with readily accessible cellular or molecular antigen. Immunotoxins display an increasing toxicity with dose, but the positioning of the toxicity gradient in relation to dose is uncertain because of the ameliorating effect of uptake by tumour. The toxicity of an antibody and its derivatives can and should be clearly documented, but a case is presented here against trials of these reagents which systematically seek MTDs with only subsidiary attention to therapeutic effects. With concurrent evaluation of therapeutic effects. With concurrent evaluation of therapy and toxicity--in studies labelled Phase I/II in the current nomenclature--it may prove just as appropriate to relate toxicity to therapeutic efficacy as to dose. PMID- 8207958 TI - Overexpression of the Raf-1 proto-oncogene in human myeloid leukemia. AB - The Raf-1 protein, a cytoplasmic serine/threonine kinase, plays an important role in signal transduction pathways. In order to examine the role of Raf-1 in human myeloid leukemia, we determined raf-1 mRNA expression by Northern blot analysis in blast cell samples from 27 acute myeloid leukemia (AML) cases and peripheral blood mononuclear cells from six healthy donors. A normal raf-1 transcript size was detected in all cases investigated. However, overexpression of raf-1 mRNA was found in 2 of 27 AML cases, both of which were erythroleukemias (AML, FAB M6). PMID- 8207957 TI - Capping of bcr-abl antisense oligonucleotides enhances antiproliferative activity against chronic myeloid leukemia cell lines. AB - Leukemia due to a chromosomal translocation offers an attractive model for the design and testing of antisense agents because the sequence at the translocation junction is unique to the leukemic cell population. Chronic myeloid leukemia is the most common such translocation-induced leukemia. We have found antisense phosphodiester oligonucleotides directed at the bcr-abl junction to be ineffective in inhibiting the growth of CML cell lines. Therefore, we have investigated the effects produced by certain structural modifications of bcr-abl antisense oligonucleotides. For assay purposes we used K562 cells which have the bcr exon 3/abl exon 2 junction and BV173 cells which have the bcr exon 2/abl exon 2 junction. We have found that 5'-capping with a dimethoxytrityl group and 3' capping with an amino-2-hydroxypropyl group confer antiproliferative activity. The enhancement of activity by capping appears at least partly attributable to exonuclease resistance since stability in serum-containing medium is increased. PMID- 8207959 TI - Serum concentrations of tumour necrosis factor-alpha during chemotherapy-induced leukopenia in patients with acute leukaemia and bacterial infections. AB - Serum concentrations of tumour necrosis factor-alpha (TNF-alpha) increase during septicaemia in previously healthy individuals. To investigate whether a similar increase in TNF-alpha can be seen in severely immunocompromised patients with acute leukaemia and chemotherapy-induced leukopenia, serum TNF-alpha was analysed in leukopenic patients with bacterial infections. Pretherapy serum levels of TNF alpha were decreased in leukaemia patients compared with healthy controls, and serum TNF-alpha levels showed a further decrease when patients developed chemotherapy-induced leukopenia. When leukopenic patients developed bacterial infections, serum concentrations of TNF-alpha increased. Serum levels of TNF alpha decreased when clinical signs of infection resolved during antibiotic therapy, but an increase occurred later in parallel with haematopoietic reconstitution. PMID- 8207960 TI - Prototypical HTLV-I/II infection is rare in LGL leukemia. AB - The etiology of LGL leukemia is not known; however, we recently detected HTLV-II in a patient with LGL leukemia. In this study, we found that sera from 6 of 28 patients with LGL leukemia were positive for HTLV-I/II using a whole virus ELISA; moreover, the ELISA-negative sera were near the positive cut-off value. Therefore, we performed additional studies on these sera using commercially available assays which can confirm and distinguish HTLV-I from HTLV-II infection. Serum from only one patient was confirmed positive using conventional criteria (HTLV-II+). Sera from 25 patients (89%) had indeterminate reactivity on Western blot assays. Of these, sera from 21 (84%) reacted to gag protein p24; 12 (48%) reacted with recombinant env protein p21e, and 10 (40%) reacted with both. We could not detect HTLV-I/II pol or pX gene sequences in these patients using polymerase chain reaction analyses, with the exception of the HTLV-II-infected patient described previously. These data show that most patients with LGL leukemia are not infected with prototypical HTLV-I or HTLV-II. The frequent reactivity of patient sera to HTLV-I/II gag protein p24 and to env protein p21e, however, suggests that a deleted or variant form of HTLV-I/II may be associated with LGL leukemia. PMID- 8207961 TI - The natural tyrosine kinase inhibitor genistein produces cell cycle arrest and apoptosis in Jurkat T-leukemia cells. AB - Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinases. We analyzed the effects of genistein on in vitro growth, cell cycle progression and chromatin structure of Jurkat cells, a T-cell leukemia line with a constitutively increased tyrosine phosphorylation pattern. Exposure of in vitro cultured Jurkat cells to genistein resulted in a dose-dependent, growth inhibition. Cell-cycle analysis of genistein-treated cells revealed a G2/M arrest at low genistein concentrations (5-10 micrograms/ml), while at higher doses (20 30 micrograms/ml) there was also a perturbation in S-phase progression. The derangements in cell-cycle control were followed by apoptotic death of genistein treated cells. Immunocytochemical analysis of cells stained with a FITC conjugated anti-phosphotyrosine monoclonal antibody showed that 30 micrograms/ml genistein effectively inhibit tyrosine kinase activity in cultured Jurkat cells. Our results indicate that the natural isoflavone genistein antagonizes tumor cell growth through both cell-cycle arrest and induction of apoptosis and suggest that it could be a promising new agent in cancer therapy. PMID- 8207962 TI - Purine metabolism in promyelocytic HL60 and dimethylsulphoxide-differentiated HL60 cells. AB - Purine metabolism was studied in the human promyelocytic leukaemic cell line HL60 both before and after differentiation by dimethylsulphoxide (DMSO) treatment in vitro. DMSO-induced differentiation had no effect on the steady-state concentration of 5-phosphoribosylpyrophosphate (PRPP), even though the activity of the oxidative segment of the pentose phosphate pathway (OPP) increased two fold and the activities of glucose-6-phosphate dehydrogenase and 6 phosphogluconate dehydrogenase were enhanced 3-6 times. [14C]-formate incorporation, on the other hand, showed that undifferentiated HL60 cells produced purines by the de novo pathway at six-fold the rate of the differentiated cells and at three times the rate measured in polymorphonuclear leukocytes (PMNs) separated from human blood. This is consistent with significantly higher activities (two to five-fold) of the key regulatory enzymes of the de novo purine synthesis pathway (PRPP synthetase, amido-phosphoribosyl transferase and adenylosuccinate synthase) in the undifferentiated cells. Labelling the cells with [14C]-hypoxanthine showed that there was an active salvage pathway in the HL60 cells which remained unaltered by differentiation. The activities of the salvage enzymes were also the same, although hypoxanthine was taken up at twice the rate by the undifferentiated cells. Human PMNs had an active salvage pathway, but their rate was five times lower than that of the HL60 cells, consistent with much lower activities (three to eight-fold) of the salvage pathway enzymes. These observations suggest that regulation of the synthesis and activities of the purine nucleotide synthesis enzymes may play an important role in the regulation of differentiation of myeloid cells. PMID- 8207963 TI - 1,25(OH)2-16ene-vitamin D3 is a potent antileukemic agent with low potential to cause hypercalcemia. AB - Compounds that induce cancer cells to differentiate are clinically effective for several types of malignancies. The 1,25-dihydroxyvitamin D3[1,25(OH)2D3(C)] induces leukemic cells, including HL-60, to differentiate and/or no longer proliferate, but it causes hypercalcemia. Development of vitamin D analogs that are more potent in their abilities to affect leukemic cells without causing greater hypercalcemia, may be useful therapeutically. A novel analog [1,25(OH)2 16ene-D3(HM)] has a double bond between C-16 and C-17; it appears to be an extremely effective antileukemic agent with the same or fewer effects on serum calciums. We define the potency of this compound and compare it with seven, previously reported, potent analogs of 1,25(OH)2D3. HM inhibited clonal growth of HL-60 cells by 50% at 1.5 x 10(-11) M. This was about equipotent to 1,25(OH)2 16ene-23yne-D3(V), about 100-fold more potent than many of the other analogs, and 1000-fold more potent than 1,25(OH)2D3. The rank order of leukemic inhibitory activity was: 1,25(OH)2-16ene-D3(HM) > or = 1,25(OH)2- 16ene-23yne-D3(V) > 1,25(OH)2-23ene-D3(EX) = 1,24(OH)2-22ene-24-cyclopropyl-D3(BT) = 22-oxa- 1,25(OH)2D3(EU) = 1,25(OH)2-24-homo-D3(ER) > 1,25(OH)2D3(C) > 1,25(OH)2-24- dihomo-D3(ES). The rank order of their effects on induction of differentiation of HL-60 cells, as measured by superoxide production and nonspecific esterase activity, was similar to their antiproliferative activities. In contrast, each analog slightly stimulated proliferation of normal human myeloid clonal growth. Serum calcium levels were the same or slightly less when either 1,25(OH)2-16ene D3(HM) or 1,25(OH)2D3 (0.0625, 0.125, or 0.25 microgram) was given intraperitoneally to mice for 5 weeks. HM bound to 1,25(OH)2D3 receptors about 1.5-fold more avidly than 1,25(OH)2D3. In fact, this vitamin D3 appears to be the most avid binder to 1,25(OH)2D3 receptors that has been identified to date. In contrast, HM had a greater than 50-fold lower affinity for the D-binding proteins as compared with 1,25(OH)2D3, thus increasing the availability of the compound for target tissues. Further differentiation experiments showed that HM was more potent than 1,25(OH)2D3 in the presence of serum, but was equipotent in serum free conditions. Taken together, our experiments suggest that 1,25(OH)2-16ene D3(HM) may be more potent than 1,25(OH)2D3(C) because of its higher affinity to the 1,25(OH)2D3 receptors and its low affinity to the D-binding protein present in serum. HM is an ideal compound for clinical studies including patients with preleukemia and other neoplasia, as well as several skin disorders, such as psoriasis. PMID- 8207964 TI - Detection of bcrabl fusion mRNA in samples of whole, unfractionated blood. AB - Using a new strategy, capture-RT-PCR, bcrabl fusion mRNA sequences were specifically and sensitively detected in samples of whole blood from leukemia patients with the Philadelphia chromosome. Sample processing required only mixing blood with the chaotropic salt, GuSCN, and mRNA was captured during a short incubation of prepared blood with an affinity membrane. Immobilized mRNA sequences were amplified without elution. No radioisotopes or Southern transfer were needed. PMID- 8207965 TI - Non-toxic DNA extraction in a clinical setting. PMID- 8207966 TI - Treatment of lymphedema. PMID- 8207967 TI - Modified Charles operation for primary fibrosclerotic lymphedema. AB - Radical excision of lymphedematous tissue with skin grafting (Charles operation) may be required for patients with advanced fibrosclerotic lower extremity lymphedema. Complications of this procedure include papillomatosis, wart formation, intractable skin ulcerations and weeping of lymph and are often considered major drawbacks of the operation. We have largely circumvented these sequelae by burying a strip of shaved split-thickness skin graft into the deep subcutaneous tissue thereby modifying the Charles operation. The strip of deepithelialized skin seemingly connects the superficial dermal lymphatics with subfascial deep lymphatics thereby facilitating lymph drainage and minimizing lymphedema accumulation and the complications outlined above. We have now treated 4 patients with advanced primary fibrosclerotic lymphedema using this modified technique. Not only were the patients improved in appearance and function with less trophic changes, but lymphscintigraphy using 99mTc-dextran also suggested improved interstitial tracer transport. PMID- 8207968 TI - Lymph, lymphomania, lymphotrophy, and HIV lymphocytopathy: an historical perspective. AB - From 1578-1628, Fabricius and his pupils, Asellius and Harvey, sequentially laid the foundations for the modern sciences of comparative anatomy, lymphology and circulation, as well as a state of lympho-philia or "-mania" which persists to the present time. Lymphomania persists because there remains a fundamental controversy and ignorance about the precise functions of lymph, lymphatics, lymph glands, lymphocytes, and the bursa of Fabricius. In 1778, William Hewson deduced that lymph effluent from lymph glands contains globular particles essential to normal body growth and tissue repair. In 1878, Claude Bernard recognized that lymph is a composite emanating from all body cells which forms the circulating blood plasma in order to sustain homeostasis throughout the internal milieu. From 1890-1960, many observers confirmed older concepts that lymph, lymph glands, and lymphocytes develop to nourish and regulate cell growth throughout the body. However, since 1960 characterization of "T-" and "B-" cells, respectively derived from thymus and the avian bursa, has revolutionized conceptual immunology, almost to the exclusion of older trophic concepts of lymph, lymph gland and lymphocyte functions. Therefore, homeostasis is considered here in terms of lymph circulation from and to respiring cells, as well as in homeostatic "failures" commonly found in persons infected with lymphotropic retroviruses. PMID- 8207969 TI - Environmental induction of tumor phenotype in a putative Kaposi sarcoma progenitor cell. AB - Many features of AIDS-related Kaposi sarcoma (AIDS-KS), e.g., multifocal lesional presentation at sites perfused by the microvasculature, suggest that AIDS-KS is initially a hyperplasia that subsequently progresses to a neoplasia. We propose that the unique AIDS environment, which contains high levels of circulating factors such as viral cytokines, is key in initiating the KS lesion. Further, we maintain that due to their physiological function, human microvascular endothelial cells (HMECs) are both likely target cells for the AIDS-related cytokines, and are putative AIDS-KS progenitor cells. Previously, we have shown that as a component of HMEC transition between proliferative and differentiated growth, HMECs modulate their nucleotide and glutathione levels. After attaining contact inhibition, HMECs enter a state of differentiation, which is characterized by cellular entrance into a G0, quiescent growth state, a decrease in cellular bioenergetic profiles, and spontaneous formation of microtubules. In contrast, when cultured in a "KS milieu", HMECs fail to differentiate. Instead, the "KS milieu" cultured cells assume a "growth relaxed" phenotype and demonstrate a lack of contact inhibition, loss of anchorage dependence, and retention of a "proliferative" bioenergetic profile despite culture confluence. Our results imply both that HMECs are responsive to AIDS-related cytokines, and that the local environment is key to instigating a relaxation of cellular growth controls. PMID- 8207970 TI - Poor photomicrographs. PMID- 8207971 TI - Characterization of ovine lymphatic endothelial cells and their interactions with lymphocytes. AB - The interaction of blood-borne lymphocytes with blood vascular endothelial cells is a fundamental component of lymphocyte circulation. The role of lymphatic endothelial cells is less certain. These studies describe the isolation, characterization and lymphocyte binding capacity of efferent lymphatic endothelial cells from ovine mesenteric lymphatic vessels. Lymphatic endothelial cells had anti-thrombin 3, von Willebrand Factor and MHC I on their surface. The cells also actively metabolized acetylated low density lipoprotein. The morphological appearance was indistinguishable from blood vascular endothelium but quite different from cultured smooth muscle cells. Lymphocyte binding to lymphatic endothelial cells was not significantly different from binding to carotid artery or jugular vein endothelial cells. The degree of binding in all cases could be enhanced by incubating endothelial cells in medium containing rh TNF-alpha (recombinant human tumor necrosis factor alpha). PMID- 8207972 TI - Announcement communicated at the International Conference on Glycol Ethers, Nancy, France, April 19-22, 1994. PMID- 8207973 TI - Detection of monosomy 7 and trisomies 8 and 11 in myelodysplastic disorders by interphase fluorescent in situ hybridization. Comparison with acute non lymphocytic leukemias. AB - Cells from 50 patients with myelodysplastic syndrome (MDS) and 20 patients with acute non-lymphoblastic leukemia (ANLL) were studied by fluorescent in situ hybridization (FISH) using alphoid biotinylated probes to detect numerical chromosome 7, 8 and 11 aberrations in interphase nuclei. FISH data were compared with cytogenetic results. Both methods were in agreement in 25/50 MDS and 20/20 ANLL cases. Trisomy 11 was found neither by cytogenetic study nor by FISH. In 11 MDS patients the percentage of abnormal cells was higher by FISH than by classical cytogenetic analysis. FISH revealed monosomy 7 which was undetectable by karyotypic study in 5-22% cells from 15 MDS patients. It also allowed the identification of two small markers and a ring chromosome in two MDS cases. FISH hence appears to be useful for the detection of minor abnormal clones and is a convenient complement to conventional cytogenetic analysis in the study of MDS. PMID- 8207974 TI - Fluorescence in situ hybridization improves the detection of monosomy 7 in myelodysplastic syndromes. AB - We performed conventional cytogenetic (CC) and interphase fluorescence in situ hybridization (FISH) analysis with an alpha satellite chromosome 7 specific DNA centromeric probe (p alpha 7t1) on bone marrow material prepared for CC in 11 controls and 80 cases of myelodysplastic syndromes (MDS). In controls, a mean of 4.3 +/- 1% of the 700 cells examined showed only one FISH signal for chromosome 7, and the finding of > 6.3% (mean +2 standard deviations) of cells with one FISH signal was considered to indicate the presence of a clone with -7. By CC, clonal 7 was found in 11 patients, whereas two patients had -7 in only one mitose (non clonal -7). In eight of the 11 cases of clonal -7 by CC, interphase FISH confirmed -7. In the remaining three patients, 5.1%, 6.3% and 18.4% respectively of the cells had one signal. Those three patients had, in addition to -7 by CC, a marker chromosome which was shown to be constituted of chromosome 7 pericentromeric material by FISH analysis on metaphase spreads (metaphase FISH). Of the two patients with non-clonal -7 by CC, one had a -7 clone by interphase FISH whereas the other patient had normal FISH results. Five of the 67 patients with no -7 mitose by CC had clonal -7 by interphase FISH, with one chromosome 7 signal in 14.4 to 39% of the cells examined. At least three mitoses with -7 were found in two of them by metaphase FISH. Three of the five patients were reexamined 12 to 17 months later: CC and metaphase FISH found no -7, whereas interphase FISH still showed a -7 clone. Three of the patients with clonal -7 by CC and by FISH were reexamined in complete hematological remission after intensive therapy. CC found no -7 and interphase FISH was normal in all three patients. Our findings suggest that interphase FISH may improve the detection of 7 in MDS. Conventional cytogenetics should still be performed in parallel to FISH, however, because of possible false negative FISH results when a pericentromeric chromosome 7 marker is present in patients with -7. Larger numbers of cases with minor -7 clones, detectable by FISH only, and longer follow up in those cases will be necessary to determine the significance of this finding, the evolution of this minor clone, and the outcome of the patients. PMID- 8207975 TI - Residual disease in B-cell chronic lymphocytic leukemia patients and prognostic value. AB - Twenty-two B-cell chronic lymphocytic leukemia (CLL) patients were investigated to evaluate residual disease in clinico-hematological remission. Residual disease was determined by monotypy of surface light-chain expression and by dual-color staining with CD5 and CD19 markers. Samples were analyzed on flow cytometer. Total CD19+ cells above 25%, the CD5+CD19+/total CD19+ cells ratio above 0.25, clonal excess above 0.4 were considered positive for residual disease. According to these immunological criteria, only four cases achieved phenotypic remission. Our data confirm that dual marker analysis is more sensitive than clonal excess and may predict an early relapse. Ig gene rearrangements were studied by Southern blot analysis using IGHJ and IGKC probes in fifteen cases. All 12 cases that retained a detectable rearrangement displayed a phenotypic residual disease. Conversely, in two cases, DNA analysis failed to detect the residual disease characterized by flow cytometry. In conclusion, this study suggests that in B CLL, dual marker analysis is sensitive in predicting an early relapse in sequential evaluations of residual disease, whereas rearranged bands are undetectable when the proportion of malignant cells is low. PMID- 8207976 TI - Analysis of mutations and expression of GAP-related domain of the neurofibromatosis type 1 (NF1) gene in the progression of chronic myelogenous leukemia. AB - We investigated mutations in the GTPase activating protein-related domain of the neurofibromatosis type 1 gene (NF1-GRD) and its expression in each phase of chronic myelogenous leukemia (CML). Samples from 45 cases in chronic phase (CP), 41 in acute phase, and four CML cell lines were examined for mutations in the NF1 GRD by single-strand conformation polymorphism (SSCP) analysis and allele specific restriction analysis (ASRA). No mutations were detected in the exon where frequent mutations have recently been reported in human tumors, namely the FLR exon. We also examined for point mutations of the N-ras gene but found no mutations either. In 23 samples from CML cases and four CML cell lines, expression of two types of the NF1-GRD transcripts, type I and type II, were examined by NF1-GRD-specific polymerase chain reaction-based densitometric analysis and by the quantitative assay with coamplification of the NF1-GRD and beta-actin transcripts. Consequently, although expression level of type I transcripts varied among the samples, type II expression was increased in CML cell lines and a minor increase in type II expression was observed in the samples in acute phase compared with CP. However, this difference in type II expression between CP and acute phase was so small that changes of NF1-GRD transcripts as well as NF1-GRD or N-ras mutations might not be responsible for the progression of CML. PMID- 8207977 TI - Expression of GATA-1 mRNA in human myeloid leukemic cells. AB - Expression of the transcription factor GATA-1, which regulates several erythroid specific genes and possibly also some megakaryocytic genes, has been previously detected in normal erythroblasts, megakaryocytes, and basophils, and in some myeloid cell lines. It has been suggested that GATA-1 may be first expressed in a common progenitor and then further activated during erythroid-megakaryocytic and basophilic differentiation and repressed during myeloid maturation. We investigated GATA-1 mRNA expression in highly purified leukemic blasts representing different lineages and stages of myeloid differentiation and in a recently established leukemic cell line, GF-D8, which exhibits morphological, cytochemical and immunophenotypic characteristics of early myeloid progenitor cells. We found GATA-1 expression in five of five myeloid and in one megakaryocytic blast crisis of CML, in four of six cases of myelomonocytic leukemias (M4 according to FAB classification), in one case of erythroleukemia (M6), whereas lymphoid blast crisis of CML and all other FAB groups were completely negative. In addition, a low level of GATA-1 mRNA was also expressed by the GF-D8 cell line. These data further support the hypothesis that GATA-1 expression may occur not only in erythroid and megakaryocytic progenitors, but also in early myeloid progenitors, and then be further regulated during lineage specific maturation. PMID- 8207978 TI - In vivo clonal evolution of pre-B to B-cell acute lymphoblastic leukemia in childhood. AB - Two cases are described that provide further evidence for clonal evolution in pre B-cell acute lymphoblastic leukemia. Two infants, whose lymphoblasts at diagnosis were morphologically subtyped as L1 and immunophenotyped as HLA DR+, CD19+, CD10+/- and C mu-, were induced and maintained in remission. One child relapsed 6 months after initiation of therapy. This time his lymphoblasts had L3 morphology and immunophenotyping demonstrated the appearance of surface immunoglobulins. The second child relapsed 18 months after initiation of therapy with a lymphomatous picture. He also had peripheral and bone marrow blasts with L3 morphology and surface immunoglobulins. A lymph node biopsy showed diffuse small non-cleaved lymphoma with a 'starry sky' appearance compatible with Burkitt's lymphoma. Only one case with a similar clonal evolution has been reported in the literature, but no surface immunoglobulins were demonstrated. The significance of clonal evolution in these cases and its potential practical implications are discussed. PMID- 8207979 TI - Lactic acidosis in a patient with B-cell non-Hodgkin's lymphoma. AB - A patient with an intermediate grade B-cell non-Hodgkin's lymphoma who presented with severe dyspnea caused by lymphoma-related lactic acidosis is described. The serum lactate and pyruvate levels paralleled the disease activity. Although oncologists are familiar with the relationship between bulky solid tumors and lactic acidosis, well-documented lymphoma cases are extremely rare. PMID- 8207980 TI - Terminal deoxynucleotidyl transferase (TdT) positivity in acute nonlymphoblastic leukemia. PMID- 8207981 TI - Routes to repopulation--a unification of the stochastic model and separation of stem-cell subpopulations. AB - In summary, we propose that the haemopoietic system consists of a hierarchy of clonogenic stem and progenitor cells and that the stochastic effect is superimposed upon these compartments. This means that (i) considerable heterogeneity can exist within major compartments without the need to invoke the existence of numerous subpopulations, and (ii) that the stochastic effect and the separation of stem cells are not totally incompatible. The unifying model offers a reasonable explanation of the situations summarized above. The clear implication of the disappearance of stem cell clones as a result of the stochastic effect is a requirement for multiple stem cells to ensure long-term repopulation in cell replacement or gene therapy. The necessary multiplicity may not be great, possibly 3-fold according to the results of Lemishka, and the scheme shown in Figure 1, but should be considered in the design and interpretation of experimental and therapeutic strategies. Other implications are concerned with the degree to which it is necessary to select 'subpopulations' of haemopoietic stem cells for transplantation or experimental work. PMID- 8207982 TI - Is acute promyelocytic leukemia a curable disease? Treatment strategy for a long term survival. AB - The major cause of early death in acute promyelocytic leukemia (APL), the high risk of a bleeding diathesis is now successfully counteracted within a few days by differentiation therapy using ATRA. Moreover, no resistance to this drug has been recorded during induction when the usual presence of PML/RAR alpha was confirmed by molecular study (some M3 cases do lack rearrangement of PML/RAR alpha). Paradoxically, a hypercoagulable clotting tendency may occur in these patients during the first month of ATRA treatment. Leucocyte activation (retinoic acid syndrome), often secondary to hyperleukocytosis, is prevented by early addition of chemotherapy when WBCs exceed defined limits, and is successfully treated by high dose corticosteroids. Routine acquired progressive in vivo resistance to all trans retinoic acid (ATRA) requires consolidation of ATRA induced complete remission (CR) with intensive chemotherapy. Prevention of relapses using maintenance therapy is questionable and has not been tested in randomized trials. Actually the event-free survival of APL patients treated by the combination of ATRA and chemotherapy is 80% at 1 year, and the cure of 50% of patients is within our reach. PMID- 8207983 TI - In vitro all-trans retinoic acid (ATRA) sensitivity and cellular retinoic acid binding protein (CRABP) levels in relapse leukemic cells after remission induction by ATRA in acute promyelocytic leukemia. AB - The current treatment of acute promyelocytic leukemia (APL, also called AML3 subtype) is focused on differentiating agents such as the vitamin A derivative all-trans retinoic acid (ATRA). This agent is a novel and very promising therapy for this disease characterized cytogenetically by a translocation t(15;17)(q21;q22) involving the alpha retinoic acid receptor on chromosome 17 and the PML gene on chromosome 15. Clinical trials have demonstrated that ATRA followed by or combined with conventional chemotherapy may be more beneficial than chemotherapy for inducing complete remission. Unfortunately, ATRA as a single agent, does not appear able to maintain patients in remission (median 5 months), and when relapse occurs resistance to a second induction of ATRA therapy is observed in almost all cases. Recently our laboratory investigated whether specific features of the AML3 cells at relapse could explain the in vivo resistance observed. We have demonstrated that AML3 patients' cells (from four patients) at relapse show high levels of CRABP, a cytosolic retinoic acid binding protein and this protein was not detected prior to ATRA therapy. Relapse-AML3 cells (n = 12) showed reduced differentiation induction when compared with 'virgin'-AML3 cells. Results from this study suggest that CRABP could modulate ATRA cellular concentrations reaching the nucleus. This induced ATRA hypercatabolytic state should be monitored during consolidation therapy and at relapse by evaluating CRABP and RA metabolite levels, in order to detect ATRA resistance in patients with AML3. PMID- 8207984 TI - TCR-beta chain gene rearrangement and expression in human T-cell development and in leukemia. AB - T-cell receptor TCR-beta gene expression is an early event during human ontogenesis since the majority of thymocytes express cytoplasmic beta chain as early as the 15th week of gestation, when a complete VDJ rearrangement and functional 1.3-kb beta gene transcript are detectable. We report here our contribution with those of others on the analysis of TCR-beta gene ontogenesis. By sequencing beta gene transcripts we have demonstrated that beta gene N-regions increase dramatically in the thymus after the 20th week and that the period between 20-30 weeks is of critical importance for the acquisition of N-diversity. A correlation between TdT and N-region expression also exists. An ordered expression of TdT and cytoplasmic beta chain occurs in humans starting around the 20th week, similar to the sequence of coordinated expression of TdT and cytoplasmic mu chains detectable in B-cell precursors. TCR-beta gene behavior in T-cell neoplasms, in 'biphenotypic' leukemias and in B-ALL is also discussed. An interesting study of seven cases of B-ALL with complete V(D)J beta gene rearrangement is analyzed, as is its implication for further analysis in B-cell leukemia. PMID- 8207985 TI - Are patients with acute leukaemia, alive and well 2 years post bone marrow transplantation cured? A European survey. Acute Leukaemia Working Party of the European Group for Bone Marrow Transplantation (EBMT). AB - We investigated the occurrence of late events (beyond 2 years) in patients with acute leukaemia who received an allogeneic (BMT) (n = 1059), or an autologous bone marrow transplantation (ABMT) (n = 656) in Europe during the period from January 1979 to December 1990. Patients with no recurrence of leukaemia at 2 years had overall 82% chance of being alive in complete remission at 9 years following transplantation regardless of the nature of the leukaemia, the status at transplant, and the type of transplant. The incidence of late relapses continuously decreased with time. The latest relapses in acute myelogenous leukaemia (AML) were observed following BMT at 6.6 years in a patient transplanted in first remission (CR1) and at 3.7 years in a patient transplanted in second remission (CR2), and following ABMT at 6 years and 5.1 years respectively. The latest relapses in acute lymphoblastic leukaemia (ALL) were observed following BMT at 4 years in a patient transplanted in first remission (CR1) and at 6.8 years in a patient transplanted in second remission (CR2), and following ABMT at 5.3 years and 4.5 years respectively. Several factors predictive for late relapse or death were identified. Patients allografted experienced a lower frequency of late relapse than patients autografted. Of the numerous other prognostic factors studied, female sex in AML, the use of total body irradiation (TBI) in ALL and status in CR1, rather than CR2-3, for both ALL and AML allografted were correlated with a lower relapse incidence. The use of TBI in ALL was also associated with a better LFS and survival. The absence of acute graft-versus-host disease (GVHD) in allografted AML correlated with better LFS and better survival, but had no influence on the relapse incidence. This study indicates that patients alive and well at 2 years post transplant have a very high probability of being cured, but the possibility of late relapse still remains. PMID- 8207986 TI - Treatment of acute promyelocytic leukemia with all-trans retinoic acid: an update of the New York experience. AB - In an ongoing study, we treated 79 patients with a molecular diagnosis of acute promyelocytic leukemia (APL) using all-trans retinoic acid (RA) for remission induction. Newly diagnosed patients received cytotoxic chemotherapy for consolidation, and previously treated patients received extended all-trans RA therapy, or a radionuclide-conjugated monoclonal antibody as post-remission treatment. Unlike studies in Europe, full-dose chemotherapy was not given during induction for patients who developed leukocytosis. Overall, 43 of 49 newly diagnosed patients (88%) and 25 of 30 previously treated patients (83%) achieved complete remission. We did not encounter de novo resistance to all-trans RA in any patient who was positive for PML/RAR-alpha rearrangements by reverse transcription polymerase chain reaction analysis. Ten patients died during induction from intracranial or pulmonary hemorrhage (six patients) or the 'retinoic acid syndrome' (four patients). The use of leukapheresis or low-dose chemotherapy (hydroxyurea or cytosine arabinoside) for drug-induced leukocytosis did not decrease early mortality. Compared to historical controls, early mortality was not affected by treatment with all-trans RA; however, both relapse free and overall survival were significantly increased. Maintenance therapy with all-trans RA was associated with short remission duration, and relapses while taking the drug were universally associated with resistance to further retinoid treatment. We conclude that the use of all-trans RA for remission induction, with or without full-dose chemotherapy, has significantly increased the survival of patients with APL. While early mortality has not yet been reduced, the avoidance of full-dose chemotherapy during induction has significantly reduced early morbidity. The major outstanding clinical issue is the development of strategies that maximize safety in high-risk patients for whom intracranial hemorrhage remains the major cause of death. PMID- 8207987 TI - Morbidity and costs of remission induction therapy with all-trans retinoic acid compared with standard chemotherapy in acute promyelocytic leukemia. AB - With the recent pressure to control health care expenditures, the costs of patient participation in clinical trials, especially in their earliest phases, have come under increasingly intense scrutiny. We therefore reviewed our experience in patients with acute promyelocytic leukemia (APL) who were treated during the first US trial of a new experimental drug, all-trans retinoic acid (RA). The purpose of the review was to evaluate parameters of patient morbidity and financial cost associated with the use of all-trans RA compared with standard chemotherapy for induction of complete remission in newly-diagnosed patients with APL. We retrospectively compared outcomes of consecutive patients treated during the first 2 years of our studies that used all-trans RA for remission induction (1990-1992) with an identical number of patients consecutively treated with standard chemotherapy (cytosine arabinoside plus an anthracycline) during the immediately preceding period (1985-1990). Responding patients in both groups received post-remission chemotherapy. Evaluation parameters included transfusions of packed red blood cells and platelets, use of anti-bacterial and anti-fungal drugs, duration of fever, time to remission, length of hospital stay, hospital charges, and both overall and relapse-free survival. Thirty patients were evaluated in each group. Complete remission was achieved in 26 patients (87%) treated with all-trans RA, and 24 patients (77%) treated with chemotherapy (p = 0.5). In the chemotherapy group, there were five early deaths (four from hemorrhage, one from sepsis); one other patient was resistant to treatment and died at 6 months. Four patients in the all-trans RA group died prior to response from complications of the 'retinoic acid syndrome'. The median time to complete response by all criteria was 41 days (range, 18-78) for the all-trans RA group and 50 days (range, 24-121) for patients who received conventional chemotherapy (p = 0.2). Looking only at patients who achieved remission, chemotherapy-treated patients required a significantly greater number of platelet transfusions (medians, 14 vs. 4; p < 0.001) and packed red blood cell transfusions (15 vs. 4; p < 0.001). Patients who received chemotherapy also experienced a significantly larger number of days with fever (13 vs. 6; p = 0.01) that was reflected in a greater median number of days on combination antibiotics (35 vs. 21; p = 0.001) and Amphotericin B (20 vs. 0; p < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8207988 TI - Nuclear lamin expression reveals a surprisingly high growth fraction in childhood acute lymphoblastic leukemia cells. AB - In an attempt to better characterize leukemic bone marrow cells of children with ALL in G0/G1, we studied the variation of the nuclear projection area (NPA) during the cell cycle. Approximately half of the increase of the nuclear volume during the cell cycle occurred before DNA synthesis. Next, we assessed by in situ hybridization (ISH) the expression of nuclear envelope type A/C and type B lamins in leukemic lymphoblast and unstimulated as well as stimulated normal peripheral blood mononuclear cells (PBMC). It was found that 82.0 +/- 16.0% of the ALL cells expressed B-type and 5.8 +/- 3.1% A/C-type lamins. The in vitro 3HdT pulse labeling index (3HdT LI) of ALL cells varied from 1.3 to 16.8%. Of unstimulated PBMC 2.9 and 1.2% expressed lamin type B and A/C, respectively. The 3HdT LI was 0.8%. In conA-stimulated PBMC, the corresponding values were 95.3 and 74.8% and 31.0%, respectively. In view of the current concepts regarding G1 events and regulation of cell proliferation, we considered B-type lamin expression an early marker for the commitment to proliferation and used it for growth fraction (GF) determinations. By this method, a surprisingly high GF was found in ALL cell populations; there was no correlation between GF and the 3HdT LI, as seen in normal cells. PMID- 8207989 TI - Molecular detection and characterization of clonal cell populations in acute lymphocytic leukemia by analysis of conformational polymorphisms of cRNA molecules of rearranged T-cell-receptor-gamma and immunoglobulin heavy-chain genes. AB - Junctional regions of rearranged T-cell-receptor-gamma (TCR) and immunoglobulin heavy-chain (IgH) genes represent an idiotypic DNA sequence for an individual lymphocytic cell, and any clone or clonal disease developing from this cell. In this study, a novel methodology for detection and characterization of clone specific DNA sequences in patients with acute lymphocytic leukemia (ALL) was developed. Junctional regions of rearranged TCR-gamma IgH genes in specimens of bone marrow aspirates of patients with ALL (precursor-B-ALL ten, T-ALL two, null ALL one; ALL not classified one), of a patient with lymphoid blast crisis of chronic myeloid leukemia, of a B-cell chronic lymphocytic leukemia, and in DNA from peripheral blood mononuclear cells of ten healthy volunteers were amplified by polymerase chain reaction (PCR). The PCR products were transcribed into complementary RNA (cRNA). Conformational polymorphisms of cRNA molecules were analyzed by non-denaturing polyacrylamide gel electrophoresis. A specific cRNA banding pattern for rearranged TCR-gamma or IgH genes was observed in all patients with lymphocytic leukemia. In contrast, analysis of DNA from healthy volunteers yielded a smear of confluent polymorphisms representing multiple different cRNA molecules. In two patients with precursor-B-ALL, cRNA banding patterns of junctional regions of rearranged TCR-gamma genes were analyzed in sequential bone marrow aspirates. The banding patterns disappeared after chemotherapy and achievement of blast clearance. This novel and rapid molecular assay offers several advantages as compared to Southern blot analyses and previous PCR based methodologies for the detection of clonal lymphocytic populations. With this methodology, studies on the clonal evolution of lymphoproliferative disorders (e.g. the prognostic significance of the emergence of additional clones) can be performed more easily than with any other traditional molecular method. PMID- 8207990 TI - Secondary chromosomal abnormalities in acute leukemias. AB - Secondary chromosomal aberrations reported in the literature were surveyed in acute myeloid or lymphoblastic leukemia (AML or ALL) with one of the following primary abnormalities: in AML, t(1;3), t(1;22), der(1;7), inv(3), t(3;5) +4, del(5q), t(6;9), -7, t(7;11), del(7q), +8, t(8;16), t(8;21), +9, t(9;11), del(9q), t(9;22), +11, del(11q), t(11;19), del(12p), +13, t(15;17), inv(16), t(16;21), i(17)(q10), del(20q), -21, +21, +22, and -Y; in ALL, t(1;14), t(1;19), der(19)t(1;19), t(4;11), del(6q), t(8;14)(q24;q11), t(8;14)(q24;q32), t(8;22), del(9p), dic(9;12), i(9)(q10), t(9;22), t(10;14), t(11;14), t(11;19), del(12p), 20, +21, and del(22q). Out of 7111 acute leukemias with clonal karyotypic aberrations, 2414 AMLs and 1078 ALLs had one of the selected primary chromosome rearrangements, and 40 and 49% of these AMLs and ALLs, respectively, displayed additional abnormalities. The type and frequency of these secondary changes were ascertained and then correlated with both the primary abnormality and the morphology or immunophenotype of the acute leukemia. The distribution of the secondary changes was clearly nonrandom. The most frequent numerical changes were -Y, -X, -7, +8, and +22 in AML and +X, +6, -7, +8, and +21 in ALL. The most common structural aberrations were del(5q), del(7q), and del(9q) in AML and dup(1q), i(7q)(q10), and der(22)t(9;22) in ALL. Some secondary changes were common to both disease groups, e.g. -7, +8, and +21, but several anomalies were restricted to either AML, such as -X, -5, and del(9q), or ALL, e.g. +X, i(7)(q10), and i(9)(q10). The type and frequency of the secondary aberrations varied within the AMLs and ALLs, not only among the different primary abnormality subgroups but also among the AML morphologies and the immunophenotypic maturation degrees of the ALLs. In general, the type of primary abnormality, rather than the differentiation stage of the acute leukemia, appeared to be instrumental in determining the type of secondary changes accruing. This conclusion was based on the finding that several primary abnormalities characterizing acute leukemias of the same morphology or immunophenotype displayed different patterns of secondary anomalies. The nonrandom, and sometimes quite specific, patterns of secondary aberrations strongly indicate that they are responsible for important phenotypic features of the tumor cell population, presumably closely associated with tumor progression. The molecular pathogenetic consequences of the secondary anomalies are unknown, but since most secondary changes are monosomies, trisomies, deletions, or isochromosomes resulting in genomic imbalances, one may hypothesize that gene dosage alterations rather than specific gene rearrangements are essential for tumor evolution.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8207991 TI - Differentiation stages of childhood acute lymphoblastic leukemias with p53 mutations. AB - Based upon in vitro evidence of p53 involvement in lymphoid differentiation, we assessed immunoglobulin (Ig) and T-cell receptor (TCR) genes in five acute lymphoblastic leukemias (ALLs) with, and 24 ALLs without p53 mutations to compare their genotypic stages. Using Southern blot analysis and complementarity determining region III polymerase chain reaction (CDRIII PCR), 18 cases of B lineage ALL and 11 cases of T-ALL were studied. Of 20 specimens from 18 B-lineage ALLs, two of four with p53 mutation and two of 16 without mutation had an unrearranged Ig and TCR genotype (p = 0.16; Fisher's exact test). Of 11 cases of T-ALL, the one case with p53 mutation had a rearranged TCR and Ig genotype and a case without mutation was unrearranged. The study indicates that p53 mutation is an infrequent feature of ALL found, nonetheless, in every genotypic subset. The p53 mutations in cases that do not further rearrange may support p53 involvement in lymphoid differentiation, but the heterogeneity in differentiation stages in cases both with and without p53 mutations suggests that regulation of early lymphoid maturation is multifactorial. PMID- 8207992 TI - [International diffusion of clinical trials carried out in Spain. An analysis based on their publication in scientific journals]. AB - BACKGROUND: Few studies have evaluated the clinical trials carried out in Spain and published in international journals. The present study has analyzed this situation over the period from 1981 to 1990. METHODS: Spanish studies including "clinical trial" as a key word present in Excerpta Medica CD (Drugs and Pharmacology) or MEDLINE in the CD-ROM version were evaluated. RESULTS: Two hundred forty-one original articles were obtained. The number of clinical trials was relatively stable from 1981 to 1986 (n = 8.15) increasing to a maximum from 1986 to 1988 (n = 64) with a posterior decrease. The languages of publication were English (51%) and Spanish (49%). A significant increase was observed in the number of articles published in English (p < 0.01) in the last five years. Phase III and IV clinical trials were the most frequent (89%) followed by those of phase II (9%) and phase I (2%). The open design predominated in the phase III-IV trials (58%) over the double blind trials (37%) and the single blind trials (5%). Among the former 70% were comparative and 57% followed randomized treatments. The clinical trials were published in 112 journals, Medicina Clinica (n = 32) and Current Therapeutic Research Clinical and Experimental (n = 6) were the most frequently used in Spanish and English, respectively. Two hundred sixty-three drugs were studied in the clinical trials, cisplatin was the most frequently studied (n = 10). The most commonly studied pharmacologic groups were antiinfectious (n = 40) and cytostatic (n = 35). The number of randomized clinical trials increased significantly after 1986 (p < 0.01). CONCLUSIONS: An increase in the number of clinical trials published in international journals was observed with preference for publication in English. The growing presence of randomized double blind clinical trials suggests an improvement in the quality of the clinical trials performed in Spain, particularly after 1986. PMID- 8207993 TI - [Estimation of energy expenditure in patients with morbid obesity]. AB - BACKGROUND: The equations available for the prediction of basal energy expenditure (BEE) may not be applicable in morbid obese individuals since the contribution of the fat free mass (FFM) over the BEE is not constant. The aim of this study was to obtain new equations for the prediction of BEE which are specific for patients with morbid obesity. METHODS: In 26 women with morbid obesity age, weight, body composition by bioelectric impedance and BEE by open circuit indirect calorimetry were determined. The BEE observed was compared with that estimated from the previously described equations. The multiple regression method was used to obtain the BEE prediction equations. RESULTS: Upon comparison of the BEE observed with the BEE estimated by the described equations a significant relation was found between both parameters. The differences were also significant except when the Harris-Benedict equation was used. Multiple regression analysis demonstrated that when the variables of body composition were included, the FFM explained 75% of the variation in BEE and on forcing the entrance of fatty mass, the explanation increased to 79%. When only the anthropometric variables were included, weight explained 69% of the variation. CONCLUSIONS: In morbid obesity, most of the equations described for estimating basal energy expenditure are not applicable. New equations are reported for the prediction of energy expenditure. PMID- 8207994 TI - [Reflexions on clinical trials in Spain]. PMID- 8207995 TI - [Ethical problems in genetic diagnosis and treatment]. PMID- 8207997 TI - [How to improve the quality of clinical trials]. PMID- 8207996 TI - [Chronic eosinophilic pneumonia in a patient treated with allogenic bone marrow transplantation]. AB - A 39 year old patient diagnosed of severe aplastic anemia and treated with allogenic bone marrow transplantation and who presented chronic eosinophilic pneumonia eight months after the transplant is presented. The patient had no previous history of asthma or atopy. Conditioning was performed with cyclophosphamide and total body irradiation. Prophylaxis of the graft versus host disease was carried out with cyclosporin and short course of methotrexate. At day 30 mild graft versus host disease appeared which spontaneously resolved. A progressive increase in the number of eosinophils was observed from day +40 reaching 1.05 x 10(9)/l at day +180 coinciding with suspension of the cyclosporine. The patient remained asymptomatic with no evidence of chronic graft versus host disease. At 8 months following allogenic transplantation the patient developed three episodes of fever, cough, moderate dyspnea and pulmonary infiltrates. Respiratory tests showed a restrictive pattern. Bronchoalveolar lavage contained 20% of eosinophils. Upon lung biopsy alveolar infiltration by eosinophils, lymphocytes and mononuclear cells was observed. Diagnosis of chronic eosinophilic pneumonia was made with initiation of steroid treatment. A drastic response was observed. The patient remained asymptomatic without recurrence and without evidence of chronic graft versus host disease. This picture may have been caused by the donor eosinophils given that retrospective evaluation demonstrated a persistent moderate eosinophilia in the donor. PMID- 8207998 TI - [Olive and sunflower oils: the dilemma on their effects on the lipid profile]. PMID- 8207999 TI - [Lung toxicity associated with gold salt treatment: experience with 4 cases]. PMID- 8208000 TI - [Surgical antibiotic prophylaxis and clinical committees]. PMID- 8208001 TI - [Anesthesia and laparoscopic surgery]. PMID- 8208002 TI - [Esophageal candidiasis in a non-immunosuppressed patient]. PMID- 8208003 TI - [Toxic effects of verapamil in chronic renal failure]. PMID- 8208004 TI - [Severe acute hepatitis caused by hepatitis A virus]. PMID- 8208006 TI - [Pentoxifylline is not useful in the prevention of toxicity associated with bone marrow transplantation]. AB - BACKGROUND: To evaluate the possible beneficial effect of pentoxifylline (PTX) on both the decrease of toxicity related to bone marrow transplantation (BMT) and the acceleration of the hematopoietic graft. METHODS: Twenty consecutive patients treated with BMT received pentoxifylline (400 mg/6 hours, orally) up to day +50 to prevent toxicity derived from BMT. A previous group of 29 consecutive patients transplanted in the same center were used as controls. The different clinical toxicities (mucositis, kidney failure, hepatic venocclusive disease, graft versus host disease, number of days with fever, day of hospital discharge and survival at day +50), the time elapsed until the hematopoietic graft and the levels of tumoral necrosis factor alpha were evaluated. RESULTS: No significant differences were observed in any of the parameters studied in the two groups of patients. CONCLUSIONS: Treatment with pentoxifylline does not prevent the toxicity derived from BMT or accelerate the hematopoietic grafting. PMID- 8208007 TI - [Development of a computer-assisted system to teach pathologic anatomy. Preliminary results]. AB - BACKGROUND: The present study describes the implantation of an interactive teaching system to improve both the active involvement of the student and the learning quality of Pathology. The preliminary results from the evaluation of such system are also reported. METHODS: Two attitude questionnaires (rating scale) were passed to a sample of 36 students of Medicine, randomly elected. These students used for 10 weeks a programme of Pathology (Interpat) assisted by computer. Moreover, the data stored after each session by the control stack of this programme are analyzed. RESULTS: The programme is positively evaluated by the users who consider it as an appropriate mode of learning Pathology. In spite of the scarce experience with computers, students have no difficulty in using this programme. 82% of students consider that they learn more Pathology with Interpat than with the traditional system of magistral classes. 63% of students believe that similar systems must be applied in other curricula. The average time of use of the system by each student has been 11 h 45 min (SD 4 h 55 min). The videodisc is the stack more used. CONCLUSIONS: There is a good acceptance of this methodology by the students, being almost no difficulty in using the programme, despite their low level of computer knowledge. The program is a potent instrument for individualizing the teaching of Pathology. The small size of the sample, accurate for a preliminary study as this is, must be take into account when generalizing the results. PMID- 8208005 TI - [Diagnosis of paroxysmal nocturnal hemoglobinuria with cytofluorometric of molecules bound to the membrane by glycosylphosphatidylinositol groups]. AB - BACKGROUND: Paroxysmal nocturnal hemoglobinuria (NPH) is a clonal disease in which a deficit in the expression of molecules bound to the cell membrane by glycosyl-phosphatidylinositol (MUGFI) groups has been demonstrated. The MUGFI are widely distributed and among them proteins regulating the action of complement may be found. The development of monoclonal antibodies (MoAb) against MUGFI may allow the introduction of a new diagnostic method in this disease and increase the sensitivity, particularly in transfused individuals. METHODS: The erythrocytic and leukocytic phenotype of 14 patients with NPH clonality demonstrated by the classic tests of sensitivity to the complement was analyzed by immunofluorescence techniques and flow cytometry with the use of MoAb which recognize MUGFI (CD55, CD59, CD14, CD16 and CD24). RESULTS: Cells with a decrease or absence of MUGFI were observed in all the patients. The defect was demonstrated in the red cells, monocytes and neutrophils of all the patients, while it was only observed in the lymphocytes of three patients. The percentage of cells with a decrease in MUGFI was variable (2-100%) as well the pattern of deficiency against the different MoAb used. The MoAb with greatest sensitivity for the detection of clonal population were the CD59 in erythrocytes, the CD14 in monocytes and the CD24 in neutrophils. The CD16 was normal in one patient and the CD55 in two. The transfusion of packed red cells did not influence the abnormal leukocyte pattern, with abnormalities even being observed in the erythrocytary CD59. The Ham test was negative in those cases in which the percentage of negative CD59 erythrocytes was lower than 5% of the total erythrocytic population. CONCLUSIONS: The study of glucosylphosphatidylinositol by flow cytometry and monoclonal antibodies is a useful technique for the detection and quantification of the nocturnal paroxistic hemoglobinuria clone even in transfused patients. PMID- 8208008 TI - [SAPHO: a syndrome in the process of development]. PMID- 8208009 TI - [Computer-assisted instruction]. PMID- 8208010 TI - [Cardiac tamponade and Kaposi's sarcoma]. AB - The case of a 31 year-old intravenous drug addict female patient with infection by the human immunodeficiency virus who had recurrent cardiac tamponade and who was diagnosed by pericardic biopsy as Kaposi's sarcoma is reported. The patient demonstrated involvement by cutaneous, mucosal, lymph node and probably pleuropulmonary Kaposi's sarcoma. Thoracic radiography, computerized tomography and echocardiography only showed the presence of pericardic effusion. Neither did the pericardic fluid obtained by pericardiocentesis provide any significant ethiologic data. Only the pericardic biopsy showed the typical lesions of Kaposi's sarcoma in this localization confirming diagnosis. This is the first case of pericardic Kaposi's sarcoma described in an alive patient and the difficulties of achieving the diagnosis of the cardiac involvement by Kaposi's sarcoma in AIDS patients are commented upon. PMID- 8208011 TI - [Report on new imaging technologies in cardiology. The General Subdirectorate of Services and Evaluation of Health Technologies. The Ministry of Health and Consumer Affairs]. PMID- 8208012 TI - [Cerebral embolism and atrial septal aneurysm]. PMID- 8208013 TI - [Clinical judgment in the cause of death]. PMID- 8208014 TI - [Cryptococcal infection of the central nervous system and blindness as its sequela]. PMID- 8208015 TI - [The sign of the sticky slippers]. PMID- 8208016 TI - [Are we efficient in the treatment of arterial hypertension?]. PMID- 8208017 TI - [Kaposi's sarcoma typical of the mediterranean region]. PMID- 8208018 TI - [Pentoxifylline in patients with AIDS and oral aphthous ulcers]. PMID- 8208019 TI - [Social-health care]. PMID- 8208020 TI - [Ethical aspects of intensive medicine. Results of an opinion survey]. AB - BACKGROUND: The aim of this study was to know the opinion of the professionals (physicians and nursing staff) of intensive medicine concerning aspects such as informed consent, family participation in health care decisions, the possibility of not undertaking resuscitation manoeuvers and limiting care in determined cases, the responsibility of decision in the case of differences in opinion, and the existence of bioethical committees. METHODS: A questionnaire with 19 questions was forwarded to which 381 professionals (183 physicians and 198 nurses) responded. Those who replied had a mean age of 36 +/- 7 years with at least one year of experience in an ICU (13 +/- 6 and 7 +/- 5 years, respectively). The male/female proportion was of 186/193 (152/30 physicians and 34/163 the nurses). The comparison of distribution study between physicians and nurses showed a level of significance of p < 0.05. RESULTS: Ninety-nine percent of the responses opted for the existence of orders of "no resuscitation" (p = NS) and 95% accepted the limitation of therapeutic effort in predetermined cases (p = 0.02); for 90% the quality of life was a factor to be considered (p = 0.02). It was agreed that informed consent should be obtained in 88% (p = 0.0008) but 54% were of the opinion that this wish was not always carried out (p = NS). Eighty nine percent believed that critical patients should be informed as to their situation and possibilities (p < 0.00001). In the case of patient incompetence 98% were of the opinion that the information should be given to relatives (p = NS) while only 67% believed that the family opinion may substitute that of the patient (p < 0.01) and when in doubt the last word corresponded to the physician (54%, p = NS) who may impose "best clinical judgement" (74%, p = NS) and in the case of a vital emergency consent or information may be passed over (88%, p = NS). Finally, 77% considered that informed consent cannot be given in all cases given that the mean sociocultural level of the patient does not allow comprehension (p < 0.005) and that Bioethical Hospitalary Committee are convenient or necessary (92%, p = NS). CONCLUSIONS: The attitude towards the key ethical aspects of health care practice with respect to the critical patients is unanimous being most influenced by factors of age and religion rather than by aspects linked to professional status. PMID- 8208021 TI - [Failure of prediction of results with APACHE II. Analysis of prediction errors of mortality in critical patients]. AB - BACKGROUND: The evaluation of the prognosis of critically ill patients by the APACHE II method is common in intensive care units (ICU). The aim of the present was to analyze the possible factors associated to errors in prediction. METHODS: A prospective study of 564 consecutive admissions in a department of intensive medical care was carried out. Prediction errors were studied by the calculation of the probability of death established after the first 24 hours of admission by means of APACHE II. The factors analyzed in relation to the prediction errors were: the diagnosis or cause of admission to the ICU, the length of the stay in the ICU, the time until possible death, the possible relation of the death with the cause of admission and the treatment given to the patients during the first 24 hours. Statistical analysis was performed with the SPSS software package with significance being determined at p < 0.05. RESULTS: Mortality was of 20.6% (116 cases) with three cut off points being chosen for probability of death (50, 70, and 90%). Accuracy of precision was 83.5%, 82.8% and 80.1%. There were 64 false survivors (mortality lower than 50%, 13.25%-64/483) and 29 false deaths (survival greater than 50%, 35.8%-29/81). Upon analysis of the cause of admission of these patients in whom there were prediction errors it was found that there were no differences among the false survivors and the false deaths. Significant differences were only detected upon comparison of the false survivors with the verified survivors, however these disappeared when the 136 cases admitted due to myocardial infarction were excluded. Neither did the length of stay in the ICU demonstrate any significant difference except among the verified and false deaths in that the stay was longer in the latter. CONCLUSIONS: The factors analyzed did not demonstrate that they may influence or be associated with errors in prediction of the prognosis of patients admitted to an intensive care unit, with these errors probably being due to errors in the system used. PMID- 8208023 TI - [Emotional components of language in multi-infarct dementia]. AB - BACKGROUND: Prosody is the faculty of language by which different meanings may be referred through variations in the tone, rhythm and accent with independence of the words and grammatical structures. Alteration of this sphere may modify the emotional components and proposals of the language. The aim of this study was to evaluate the existence of aprosody in a series of patients with multiinfartion dementia, quantify the disorder and ascertain the factors to which it is related. METHODS: Fourteen patients with criteria of multiinfarction dementia were included in the study. Aprosody was evaluated according to the Monrad-Krohn criteria. Neuropsychological examination included the MiniMental State Examination, the Blessed scale and the Hachinshi ischemic scale. RESULTS: Changes were seen in the prosody of 13 patients. Upon univariant statistical analysis a significant correlation was observed between the grade of alteration in prosody and the deterioration observed in the MiniMental and Blessed scale. This finding was confirmed following correction of the influence of depressive symptoms, age and time of evolution by multivariant analysis. CONCLUSIONS: The disturbances in prosody are a sensitive indicator of right hemisphere lesion in vascular dementia and are fundamentally related with the degree of neuropsychological deterioration. PMID- 8208022 TI - [Validity of 6 indirect methods to assess treatment compliance in arterial hypertension]. AB - BACKGROUND: For adequate control of high blood pressure (HBP) the therapy indicated must be correct, with effective medication which must be taken as required. At a collective level methods to evaluate patients' compliance of the above are necessary since without the same the efficacy of the drugs cannot be determined. In this study methods allowing the clinic to easily quantify patient fulfillment were sought. METHODS: Six indirect methods were used to evaluate therapeutic compliance: 1) self communicated compliance (SC), 2) appointment attendance (AA), 3) degree el control obtained in the blood pressure (DC), 4) Morinsky and Green tests (M-G), 5) patient's knowledge of the disease (PK) and 6) doctor's judgement on patient's compliance (DJ). All the above were applied to 152 hypertense patients randomly selected from the Health Centers of Alfaz and Alicante (Spain). Concordance with the compliance obtained from the "counting of tablets" in the patient's home and by surprise were evaluated by double entry tables. RESULTS: The SC is the method which obtains greatest specificity (96.7%), exactness (73%), probability of low compliance (88%) and percent of probability of low compliance (11.3%). The PK had greatest sensitivity (83.3%) and greater probability of high compliance (83.6%) and percentage of probability of high compliance (0.3%). The SC (23.1%), AA (1.3%) and the DJ (7.5%), overestimate good compliance. The M-G test (7.9%) and the PK (20.4%) overestimate had compliance. CONCLUSIONS: In this study self communicated compliance and patient's knowledge of disease were the methods which provided the best indicators of validity to measure therapeutic compliance in high blood pressure in outpatients, although there is the inconvenience of significantly over and under estimating good and bad compliance. PMID- 8208025 TI - [New treatments in rheumatoid arthritis]. PMID- 8208024 TI - [Limiting treatment to critical patients]. PMID- 8208026 TI - [Additional declarations of the International Committee of Medical Directors (the Vancouver Group)]. PMID- 8208027 TI - [Malignant mesothelioma]. PMID- 8208028 TI - [Disseminated infection caused by Mycobacterium avium complex and stereotaxic cerebral biopsy. Diagnosis and treatment in a patient with AIDS]. PMID- 8208029 TI - [Asthma as the first manifestation of hepatic hydatidosis]. PMID- 8208030 TI - [Staphylococcal arthritis of the knee secondary to femoral artery catheterization]. PMID- 8208031 TI - [Early resuscitation in cardiorespiratory arrest caused by drowning]. PMID- 8208032 TI - [Narcotics, opiates, or opioids?]. PMID- 8208033 TI - [Extrabronchial small-cell carcinoma]. PMID- 8208034 TI - [Annual incidence and control of nosocomial infections in a county hospital]. AB - BACKGROUND: The recommendation of Centers for Disease Control that hospitals must have a person trained in infection control per 250 beds has been understood as a law of all or nothing hindering implementation of hospital infection surveillance and control programs in small hospitals. Since the importance that small regional hospitals have in the Spanish Health System, the aim of this study is to describe the magnitude and characteristics of nosocomial infections (NI) in a small regional hospital in case this position needs being reconsidered. METHODS: The study was carried in Hospital de Calatayud, a small regional hospital of 122 beds belonging to Health Area III of Aragon. All the NI that occurred during 1992 were recorded by means of an uninterrupted system of prospective surveillance based on a multirecord revision. Both of the Accumulate Incidence of NI (AINI) and Accumulate Incidence of Patients with one or more NI (AINP) were calculated and the main variables associated with NI were described. RESULTS: Altogether, 298 NI were detected in 242 patients during that year. The AINI was 7.1% and the AINP was 5.8% with a mean of 1.2 (SD = 0.6) HI per infected patient. The most frequent types of NI were urinary tract infection, surgical wound infection and lower respiratory tract infection. Some pathogen microorganism were identified in 43% of NI. The microorganisms most frequently associated with NI were Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Mortality associated with NI was 11% and the average stay of patients with some NI was 22.9 days (SD = 22.1). CONCLUSIONS: Results point out the need for implementing hospital infections surveillance and control programs in small hospitals too. PMID- 8208035 TI - [Cancer mortality trends in Catalonia: 1975-1990]. AB - BACKGROUND: Cancer is one of the most important health problems in developed countries. The aim of this paper is to analyze mortality trends due to cancer in Catalonia from 1975 to 1990. METHODS: Cancer mortality trends have been studied for each sex separately. Rates were standardized by direct method, using world population as standard; also, truncated (35-65 years old) and cumulative rates (0 74) were calculated. Annual percentage of change was estimated from a Poisson's regression model. RESULTS: An increase of cancer mortality was observed between 1975 and 1990 among men but not in women. Lung cancer is the main cause of death from cancer in men and breast cancer in women. Both these cancers showed a significative increase in their mortality during the period of study. Among men, there is a significative increase in the following cancers: oral cavity, colon, pancreas, melanoma, non-Hodgkin's lymphoma and myeloma; and there is a decrease in the following cancers: stomach, testicle and brain. Among women, there is a significative increase in cancer mortality due to the following: ovarian, colon, pancreas, melanoma and non-Hodgkin's lymphoma; while decrease in the following: stomach, liver and uterus. Also, lung cancer mortality among women is decreasing. CONCLUSION: The increasing trend observed in lung cancer mortality rates among men and in breast cancer among women are the main causes of concern. Therefore, priorities in cancer control underlined by this analysis should include emphasis on smoking control and developing breast cancer screening. PMID- 8208036 TI - [Prognostic value of 2 patient classification systems: APACHE II and diagnosis related groups]. AB - The APACHE II system classified patients on the basis of the severity of their disease, while the groups related with the diagnosis (DRG) are classified according to the consumption of resources. Nonetheless, the relative DRG weight (RWDRG) may be related with severity given that the most severe patients are also usually the most expensive. The aims of the study were: 1) verify the ability of DRG to measure clinical severity and 2) compare the prognostic value of both systems. METHODS: A transversal cut off was performed (316 consecutive admissions in intensive care units [ICU] with 23 exclusions due to unclear final evolution) with the patients being classified according to final hospital evolution in survivors and deaths. Each patient was given an APACHE II score corresponding to the first 24 hours in the ICU. Parallelly the cases were grouped in the corresponding DRG in accordance with the CIE-9-MC codification of their discharge report. The comparison of the means was carried out with the Student's t test, with the determination of prognostic values being performed by discriminant analysis. RESULTS: The survivors had an APACHE II score of 9.5 +/- 5.5 and the deaths of 22.5 +/- 7.8 (p < 0.0001). The RWDRG of the survivors was 1.4 +/- 0.9 and that of the deaths of 2.0 +/- 1.0 (p < 0.0001). On inclusion of all the patients the APACHE II prognostic value was 85.3% and the RWDRG 68.9% and both 84.6%. In the group of patients with a RWDRG lower than 1.6 the prognostic value of the APACHE II was of 87.6% and the RGRDW 72.0% and both 90%. In the group with RWDRG greater than 1.6 the prognostic value of the APACHE II was 85.1%, the RWDRG 73.0% and both 83.2%. CONCLUSIONS: The system of the groups related with diagnosis indirectly measures clinical severity. APACHE II is significantly superior to the system of groups related with diagnosis with regard to prognostic value. The use of both systems together does not improve the prognostic value of APACHE II. PMID- 8208037 TI - [Nocturnal fall in arterial blood pressure in normotensive subjects: individual characteristic or the effect of daily activity?]. AB - BACKGROUND: The interpretation of the absence of a nocturnal fall in blood pressure (BP) (non-dipper condition) and its possible prognostic value are not clear. One possible hypothesis to be analyzed is whether the condition of non dipper is due or not to the daily activity. METHODS: Ninety-five doctors, 47 of whom were females, whose age ranged between 24 and 46 years participated in the study. Ambulatory monitoring BP were programmed to be randomly carried out on call and on a day-off with measurements intervals of 15 min. Mean systolic BP (SBP), diastolic BP (DBP) and heart rate (HR) were considered as measurement parameters for every period: 24 h, awake and sleep. Sleep period was considered as one of no less than 2 hours, nocturnal BP fall was defined as the difference between awake and sleep means, and dipper condition as a systolic decrease greater than 10 mmHg and diastolic decrease greater than 5 mmHg. RESULTS: The mean nocturnal BP fall on the day-off was of 15% and 13% (SBP and DBP) and while on-call it was 18% and 15% respectively (p < 0.001). In absolute values the SBP decreased 21 +/- 10 mmHg and 18 +/- 10 mmHg and the DBP 11 +/- 6 mmHg and 10 +/- 5 mmHg, on-call and day off respectively (p < 0.001). The percentage of subjects with decrease lower than 10/5 mmHg was different in each of the two days (8% and 12%), however only one individual maintained the non-dipper condition in both period, although he reported many interruptions in the sleep. No association was established between the nocturnal BP fall and other variables (age, sex or family history of hypertension). CONCLUSION: The non-dipper condition is changeable and is related to the activity carried out by the subject while awake, as well as the quality of sleep. It does not seem to be associated with inherent variables of the individual such as family history of hypertension, age or sex. PMID- 8208038 TI - [Hypertension, low-sodium diet and its metabolic effects]. PMID- 8208039 TI - [Primary prevention of toxoplasmosis in patients with HIV infection]. PMID- 8208040 TI - [Changing the natural history of essential arterial hypertension by antihypertensive treatment]. PMID- 8208041 TI - [Autonomic disorders of central origin]. PMID- 8208042 TI - [Direct immunofluorescence in the diagnosis of mucocutaneous infections caused by herpes simplex virus]. PMID- 8208043 TI - [Low-molecular-weight heparin in a patient with heparin-induced thrombocytopenia and a cardiopulmonary bypass]. PMID- 8208044 TI - [Sleep apnea syndrome, catecholamines and arterial hypertension]. PMID- 8208045 TI - [Multicentric clinical trials: an attempt to homogenize criteria in the use of subjective measurements]. PMID- 8208046 TI - Tumor growth delay by laser-generated shock waves. AB - The antiproliferative effect of laser-generated shock waves (L-SW) was investigated on a human renal cell carcinoma, RC-8, grown subcutaneously in the nu/nu mouse. The RC-8 is characterized by the syndrome of humoral hypercalcemia of malignancy (HHM) associated with profound cachexia, increase of serum Ca level, hypophosphatemia, and an enhancement of serum parathyroid-like peptides. In this model system, the effects on cachexia and tumor growth were studied after a series of pulses (3-200) generated by a Candela LFDL/3 equipped pulsed-dye laser with optical fiber guided through a hypodermic needle with a 45 degrees angle bended tip, stuck through the skin of the mouse, and positioned directly below the tumor. The antitumor effect, expressed as a delay of tumor growth, was found to be dependent on number of pulses applied, tumor size, and growth rate (alpha). Treatment of RC-8 with alpha = 0.21 was effective only after 200 pulses combined with a tumor volume smaller than 100 mm3. Under these conditions a growth delay of approximately 8 days was observed, paralleled by delay of animal weight loss (cachexia). Under conditions of a decreased growth rate of RC-8 (alpha = 0.13), the susceptibility toward L-SW was found to be increased, expressed by a suppression of tumor growth after 100 pulses. However, no L-SW associated delay of cachexia was observed under these latter conditions. PMID- 8208047 TI - Use of the holmium:YAG (Ho:YAG) laser for treatment of superficial bladder carcinoma. AB - This is the first North American report describing the use of the holmium:YAG (Ho:YAG) laser to treat patients with superficial bladder carcinoma. Fifteen patients, with a total of 52 recurrent superficial bladder tumors, underwent endoscopic laser photoablation of their lesions. No intraoperative or delayed complications occurred. At follow-up cystoscopy performed 3 months after lasing, four patients (27%) were without disease; eight patients (53%) had out-of-field recurrences; and three patients (20%) were classified as having in-field recurrences. We conclude that using the Ho:YAG for endoscopic treatment of patients with superficial bladder tumors is both feasible and clinically useful and that the lack of perceived pain or discomfort during lasing, as well as the lack of need for an in-dwelling urethral catheter, makes it advantageous for selected patients over conventional electroresection techniques. PMID- 8208048 TI - Toxicity of photodynamic therapy with photofrin in the normal rat brain. AB - The widespread acceptance of photodynamic therapy (PDT), a potential adjuvant brain tumor therapy under clinical evaluation since 1980, has been partially restrained by its potential toxicity toward normal brain tissue. This study examined PDT-produced injury of normal rat brain as a function of photosensitizer dose. Brain injury was characterized by correlating measurements of the area of cerebral edema using T2-weighted magnetic resonance images, measurement of brain water content at the lesion site, microscopic examination of histological sections through the PDT lesion, and by evaluation of the area of blood brain barrier (BBB) disruption using computerized morphometric analysis of the region of Evans blue (EB) dye-labelled albumin extravasation. Monochromatic red light (630 nm) was delivered intracerebrally using a 5-mm-long cylindrical, diffusion tip optical fiber at a constant energy dose of 15 joules. A Photofrin dose of 2 mg/kg of body weight produced a transient breakdown in the blood brain barrier around the site of the implanted optical fiber demonstrated by magnetic resonance imaging (MRI), extravasation of EB dye and pallor on hematoxylin and eosin stained microscopic tissue sections. A much larger area of BBB disruption was seen at a dose of 4 mg/kg of Photofrin, and this drug dose resulted in significant permanent brain injury. In this model, a Photofrin dose of 4 mg/kg body weight is not tolerated by the normal brain. PMID- 8208049 TI - Microarterial anastomosis using a noncontact diode laser versus a control study. AB - A series of direct carotid end-to-end laser anastomosis vs. direct manual suture was carried out on a series of 70 Wistar rats (mean weight 260 g). Both common carotids (0.8-1.2 mm) were sectioned and repaired. The left side (n = 70) was submitted to laser-assisted microvascular anastomosis (LAMA) performed by means of a diode laser device (wavelength 830 nm and power output 3 W in continuous wave) without chromophore. The right side (n = 70) underwent a control manual suture (CMA). The diode laser energy was delivered into a micromanipulator coupled to a Zeiss operating microscope with a focused spot of 300 microns in diameter. After placement of three 10.0 stitches for edge coaptation, the LAMA was achieved using laser shots (average 3) of 500 mW power, 4.5 s duration, and 700 W/cm2 irradiance each. The CMA was performed by means of six 10.0 stitches. The good vascular flow was confirmed by Doppler spectral analysis (n = 466) carried out from day 0 to day 90. Light and scanning electron microscopy (n = 82) showed that re-endothelialization after LAMA was gaining ground on day 3, whereas collagenous network developed in the media scar by day 10. In contrast, after CMA the arterial repair was delayed on day 20, inducing a media fibrotic scar. The patency rate was 93% in both anastomoses. The shorter operating time (13 min for LAMA vs. 22 min for CMA) and the noncontact laser technique are the main intraoperative advantages. The technical benefits of the diode laser are pointed out. PMID- 8208050 TI - Autofluorescence spectroscopy using a XeCl excimer laser system for simultaneous plaque ablation and fluorescence excitation. AB - Laser-induced fluorescence may be used to guide laser ablation of atherosclerotic lesions. This study was performed to evaluate arterial autofluorescence spectroscopy in vitro using a single XeCl excimer laser (308 nm) for simultaneous tissue ablation and fluorescence excitation. The laser beam was coupled to a 600 microns silica fiber transmitting 40-50 mJ/mm2 per pulse. The fluorescence radiation emanating retrogradely from the fiber was collected by a concave mirror spectroscopic analysis over a range of 321-657 nm. The arterial media (n = 26), lipid plaques (n = 26), and calcified lesions (n = 27) of aortic specimens from ten human cadavers were investigated in air, saline, and blood. Whereas the spectrum of calcified lesions changed with the surrounding optical medium, the other spectra remained constant. In air and blood, the spectra of arterial media, lipid plaques, and calcified lesions could be differentiated qualitatively and quantitatively (P < 0.0001). In saline, there was no clearcut spectroscopic difference between lipid plaques and calcified lesions. However, normal arterial media and atherosclerotic lesions (lipid plaques plus calcified lesions) could still be discriminated. Thus spectroscopy and plaque ablation can be combined using a single XeCl excimer laser. These encouraging results should stimulate further studies to determine the potential use of this approach to guide laser angioplasty in humans. PMID- 8208051 TI - Tissue optical property measurements: overestimation of absorption coefficient with spectrophotometric techniques. AB - This study examines the validity of optical property measurements by comparing surface temperatures rises predicted by a well-tested mathematical model with temperatures measured experimentally during laser irradiation. Analysis is based on the early temperature response that is proportional to the absorption coefficient. The results of the investigation suggest that values for tissue absorption coefficient can be greatly overestimated when current spectrophotometric techniques are used. This seems especially true when a broad light beam and a low port-to-beam-size ratio are used for transmission and reflection measurements with an integrating sphere. PMID- 8208052 TI - Temperature dependence of the absorption coefficient of water for midinfrared laser radiation. AB - The dynamics of the water absorption peak around 1.94 microns was examined. This peak is important for the absorption of holmium and thulium laser radiation. To examine the effect of temperature on the absorption coefficient, the transmission of pulsed Ho:YAG, Ho:YAG, Ho:YSGG, and Tm:YAG laser radiation through water of 22 degrees C, 49 degrees C, and 70 degrees C was measured as a function of the thickness of the water layer. From these data the absorption coefficients were determined at the three wavelengths. We found that at all three wavelengths, the absorption coefficients decreased when increasing the temperature. Second, the absorption spectrum of water was measured from 1,850-2,150 nm with a spectrophotometer. It was found that the absorption peak at 1.94 microns (at 22 degrees C) shifts to shorter wavelengths with increasing temperatures, to 1.92 microns at 70 degrees C. A model was developed to predict the temperature distribution incorporating the dynamic change in absorption coefficient. The temperature distributions are compared to the predictions of a model assuming constant optical properties. It is shown in this study that the dynamics of the absorption coefficient has a significant influence on the expected zone of damage and ablation parameters in the 2-microns wavelength range. PMID- 8208053 TI - Effects of various laser types and beam transmission methods on female organ tissue in the pig: an in vitro study. AB - The purpose of this in vitro study was to investigate and compare effects of various laser types (CO2, Argon, Erbium:YAG, Erbium:YSGG, and Holmium:YAG) and laser beam transmission methods (optical lens and flexible fiber) on ovarian and uterine tissue of the pig. The Erbium laser radiation was transmitted through Zirconium fluoride fibers (ZrF4). To circumvent the low mechanical stability of these fibers, we developed a special microlens system, which refocuses the radiation and protects the distal end from damage. Tissue lesions were performed with 1 and 5 joule. Histologic analysis of acute Er:YAG laser lesions reveal precise cutting effects with a minimal thermal damage zone of 40 microns and a high damage resistance of the fiber microlens systems. The extent of thermal damage caused by the Erbium:YSGG and CO2 laser is about two times larger, whereas the Argon and Holmium laser tissue lesions show a damage of the surrounding tissue of 200-300 microns. This study suggests that for precise cutting and coagulation, Erbium and Holmium lasers transmitted via our modified fiber tip may render the use of these lasers possible in a wide range of laparoscopic surgery applications. PMID- 8208054 TI - Thermal side effects of fiber-guided XeCl excimer laser drilling of cartilage. AB - We examined thermal effects during ablation of human joint cartilage using two XeCl excimer lasers with pulse durations of approximately 20 ns and 60 ns. An increase in radiant exposure or repetition rate caused a rise in tissue temperature up to 82 degrees C at a 100-microns distance. With increasing distance from the crater edge, the temperature dropped exponentially. Radiant exposures higher than 1.8 J/cm2 and repetition rates above 20 Hz lead to a formation of hot gaseous products escaping from the laser crater. When osteoarthritic cartilage is irradiated, these gases spread inside the tissue causing a temperature rise of > 50 degrees C at a distance of 1 mm from the crater edge. In the contact mode, we found a linear rise of ablation rate with increasing repetition rate both in air or saline. But ablation rates in saline were only half the rates achieved in air. Both phenomenons can be explained by additional thermal effects of excimer lasers working in the range of higher repetition rates and pulse energies. PMID- 8208055 TI - Disposition and metabolism of Ro 24-4736 in the rat. AB - Ro 24-4736, a new platelet activating factor antagonist, is currently under preclinical and clinical development. The tissue distribution of the 14C-label in male rats following a single intravenous dose of 1.0 mg/kg of 14C-Ro 24-4736 indicated appreciable uptake by the liver, kidney, heart and gastrointestinal tract. Peak plasma and tissue concentrations were seen at 5 minutes after dosing except for the small intestine (4 hrs) and abdominal fat, stomach and large intestine (4 hrs). Thereafter, the 14C-label rapidly declined in all tissues. At 48 hours, only 3.5% of the dose was present in the tissues, and 6.1% in the lumen of the gastrointestinal tracts. The excretion of 14C was essentially completed; 94% of the administered 14C was excreted in the feces and 4.0% in the urine. Overall recoveries of the administered 14C label ranged from 96 to 116%. The purified major 14C-labelled component in the fecal extracts yielded essentially the same NMR spectrum as authentic Ro 24-4736 which accounted for 11% of the dose. In vitro incubations of Ro 24-4736 with rat liver 9S supernatant in an NADPH generating system produced two metabolites. NMR spectra indicated that one metabolite was hydroxylated at carbon-1 while the other one contained a hydroxyl at carbon-10 of the parent molecule. Interestingly, the sites of hydroxylation were at carbons C1, and C10 bearing the protons guarding the bay area of the phenanthrenoid ring, rather than carbons of the phenyl-methyl thienotriazolodiazepine moiety. PMID- 8208056 TI - The opposing effects of an inhibitor of nitric oxide synthesis and of a donor of nitric oxide in rabbits undergoing myocardial ischemia reperfusion. AB - We observed that N-nitro-L-arginine (NOLA), a nitric oxide biosynthesis inhibitor, exacerbated necrosis in the rabbit heart during ischemia-reperfusion while 3-morpholino-sydnonimine-hydrochloride (SIN-1) (a nitric oxide donor) reduced myocardial damage in the same model. In rabbits undergoing 1-h ligation of the anterior ventricular coronary artery, a single bolus injection of NOLA (30 mg/kg) or continuous infusion of SIN-1 (3 mg/kg) were introduced into the post ischemic heart immediately before 4-h reperfusion. Against negligible necrosis in 6 sham-operated control animals, and 33.8 (SD 13.5)% necrosis in the area at risk for the saline control group (n = 8), the NOLA-treated group (n = 8) had a necrosis of 44.3 (SD 8.6)% whereas the SIN-1-treated group (n = 10) showed a necrosis of 16.8 (SD 4.9)% (both with p < 0.05 vs saline control group). The pressure-rate index increased in the NOLA-treated group but decreased in the SIN 1-treated group. These data support the contention that a nitric oxide donor is an effective cardioprotector during ischemia-reperfusion in vivo. PMID- 8208057 TI - Differences in isoproterenol-stimulated melatonin production by perifused rat pineal glands: time dependent effects and role of enantiomeric forms. AB - The perifusion of rat pineal glands removed at different times of the light-dark cycle showed a greater beta adrenergic-stimulated production of melatonin in glands obtained at the beginning of either the light or the dark stage. The effect of isoproterenol was found dependent upon its enantiomeric forms (-, +/-, +). The relative order of potency was (-) > (+/-) > (+) enantiomer. These results show that the response of pineal beta-adrenergic receptors to isoproterenol is stereospecific and circadian stage dependent. PMID- 8208058 TI - Pharmacokinetic properties of nitroxide-labeled albumin in mice. AB - We have conjugated bovine serum albumin (BSA) with a pyrrolidinyl nitroxide and report on the in vivo pharmacokinetic properties of this conjugate in mice. In vivo EPR measurements of nitroxide were obtained after intravenous injection of 30 mg of labeled BSA by analysis of the nitroxide signal from the tails of mice. Following in vivo nitroxide measurements, the animals were sacrificed by exsanguination and organs were removed for determination of nitroxide levels. The level of nitroxide as determined by in vivo measurements declined exponentially with time and had a half-life (t1/2) of 7 hours. Blood nitroxide levels also declined exponentially with time with an initial t1/2 of 70 minutes and a terminal t1/2 of 10 hours. Nitroxide concentration varied among different organs; no nitroxide was detected within brain whereas lung had high concentrations of nitroxide. Liver and kidney both had relatively low levels of oxidized nitroxide, though total nitroxide (reduced plus oxidized) accumulated in the kidneys with time. Nitroxide-labeled BSA was well tolerated by the mice, is relatively stable, and is mainly confined to the intravascular space. Nitroxide-labeled albumin may be useful as a contrast agent for MRI or EPR imaging. PMID- 8208059 TI - Behavioral effects of the novel tropane analog, 2 beta-propanoyl-3 beta-(4 toluyl)-tropane (PTT). AB - In vitro studies have demonstrated that a novel tropane analog, PTT, in which both of the esters of cocaine have been removed is 20 times more potent than cocaine and more selective than cocaine in binding to dopamine transporters. The present studies compared the ability of PTT and cocaine to stimulate locomotor activity in rats. The intraperitoneal administration of PTT and cocaine to male Fisher-344 rats produced dose-dependent increases in spontaneous locomotor activity and stereotypic behaviors. PTT was 10-20 times more potent than cocaine in this behavioral assay, closely paralleling its potency relative to cocaine in dopamine transporter binding and uptake assays in vitro. PTT, however, elicited a qualitatively different profile of stereotypic behaviors, and PTT had a longer duration of action than cocaine. These results show how changes in kinetics and selectivity of tropanes can affect stimulant-elicited behaviors. PMID- 8208060 TI - The pharmacokinetics and liver metabolism of N-hydroxy-3,4 methylenedioxyamphetamine (N-OH MDA) in rats. AB - The metabolism and disposition of N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA) was studied by utilizing rat liver slices as well as by intravenous pharmacokinetic studies in rats. In the liver slice experiments, N-OH MDA (16 micrograms/ml) was incubated with rat liver slices and the disappearance of N-OH MDA and the appearance of MDA were observed over 2 hours. Drug and metabolites were assayed by a reverse phase high performance liquid chromatographic procedure including a C8 column and UV detection. N-OH MDA disappeared from the plasma at an apparent first-order rate with a t1/2 of 36.3 +/- 8.4 min. By the end of 2 hours, approximately 85% of the N-OH MDA was biotransformed to MDA. Following placement of jugular cannulas in rats, a dose of 15 mg/kg of N-OH MDA was administered intravenously. With rapid blood sampling, a t1/2 of 0.86 +/- 0.12 min was observed for N-OH MDA. A total body clearance of 9.09 +/- 2.06 L/hr/kg and a volume of distribution of 0.184 +/- 0.022 L/kg were noted. Plasma concentrations of MDA were observed after the N-OH MDA dose to rats. The MDA t1/2 after N-OH MDA dosing was 1.68 +/- 0.29 hours with peak plasma concentrations at 8 min. No other major metabolites could be detected in liver slice, plasma, or urine samples. Both sets of studies demonstrate the rapid conversion of N-OH MDA to MDA in rats. PMID- 8208061 TI - Neurokinin receptor subtypes characterized by biological assays. AB - Neurokinin receptors have been characterized by biological assays using naturally occurring and selective agonists as well as peptide and non peptide antagonists. Six preparations have been used: the rabbit vena cava and the rat urinary bladder, treated with a NK-2 receptor antagonist for the NK-1 receptor, the rabbit pulmonary artery and the hamster urinary bladder for the NK-2, the rat portal vein and the guinea pig ileum, treated with a NK-1 receptor antagonist, for the NK-3. Treatment with antagonists was required because of the presence (in some preparations) of two functional sites contributing to the biological effect. Differences in the order of potency of agonists between each couple of receptors have been demonstrated, especially with tachykinins and the selective agonists. Such differences are even more evident with antagonists, some of which show apparent affinity (pA2) values 1.5 to 3 log units higher in one than in the other member of each couple. Based on data obtained in pharmacological experiments, it is concluded that NK-1, NK-2 and NK-3 receptors show differences strong enough to justify the assumption that their coding and/or expression diverge among species. PMID- 8208062 TI - Antioxidant administration to the mother prevents oxidative stress associated with birth in the neonatal rat. AB - In the fetal-to-neonatal transition, important circulatory and respiratory changes ensue which lead to oxidative stress evidenced by changes in glutathione status. Administration of N-Acetyl-Cysteine (NAC), a glutathione precursor, to the mother might be a rational approach to protect the fetus against oxidative stress. We have found that NAC administration to pregnant rats partially prevents the change in hepatic GSSG that occurs in the fetal-neonatal transition: GSSG increased 11-fold (from 1 to 12 nmol/g) in controls and less than two-fold (from 5 to 9 nmol/g) in animals exposed to NAC in utero. The GSH/GSSG ratio in liver of NAC-treated newborns was 411 +/- 216 and in liver of controls it was 283 +/- 176. Thus, the oxidative stress that occurs in the fetal-to-neonatal transition is partially prevented by oral NAC administration. PMID- 8208064 TI - Chemical mediator release and surface marker expression of hepatic macrophages in rats with CCl4-induced liver cirrhosis. AB - The present study was performed to analyze possible functional alterations of hepatic macrophages (HM phi) in rats with carbon tetrachloride (CCl4)-induced liver cirrhosis. HM phi from rats injected with CCl4 for 13 weeks and cultured for 24 hours released less than normal amounts of prostaglandin E2 (PGE2) and tumor necrosis factor (TNF) and very large amounts of interleukin-1 (IL-1). In rats injected with CCl4 for 9 weeks, only PGE2 production was reduced. Interleukin-2 receptor (IL-2R), Ia antigen and asialo GM1 antigen expressions on HM phi from both the 9- and 13-week groups were significantly decreased. IL-2R and Ia antigen expressions showed larger decreases in the 13-week group. Thus, it is concluded that HM phi derived from CCl4-induced cirrhotic livers show a functional alteration in the release of cytokines (except for IL-1) and a decrease in surface marker expression, as cirrhosis advances. These results should provide a basis for further investigation into the host-compromised status in the presence of liver cirrhosis. PMID- 8208065 TI - Transport of thyrotropin-releasing hormone across rat alveolar epithelial cell monolayers. AB - It has been recently shown that epithelial cell monolayers of rat type II pneumocytes cultivated on tissue culture-treated polycarbonate Transwell filters are tight (> 2,000 ohm-cm2) and exhibit morphological and phenotypic characteristics of in vivo type I pneumocytes. We studied, utilizing these tight monolayers, the transepithelial transport of thyrotropin-releasing hormone (TRH). Either [125I]TRH or [3H]TRH was used to measure the transalveolar epithelial radiolabel fluxes across the monolayer. Radiochromatography was performed, utilizing reverse-phase HPLC techniques, to determine the presence of TRH and its subspecies in dosing, donor and receiver fluids. The apparent permeability coefficient (Papp) estimated from 125I-radiolabel fluxes was approximately 1.7 x 10(-7) cm/sec in both the apical-to-basolateral (AB) and basolateral-to-apical (BA) directions. In contrast, the Papp for 3H-radiolabels was approximately 4.2 x 10(-7) cm/sec in both directions. Radiochromatography results indicated that neither apical nor basolateral receiver fluid collected at the end of 4 h flux studies contained metabolites of [125I]TRH or [3H]TRH. In the presence of 1,000 fold excess of unlabeled TRH in the donor fluid, the Papp of neither [125I]- or [3H]-TRH in either direction was altered. These data taken together provide evidence for restricted diffusional transport of intact TRH across the rat alveolar epithelial cell monolayer, most likely via paracellular pathways. Thus, it appears that TRH delivery via pulmonary alveolar epithelium in the distal airspaces of the mammalian lung may be feasible without significant interference from peptidase activities. PMID- 8208063 TI - Gou-teng (from Uncaria rhynchophylla Miquel)-induced endothelium-dependent and independent relaxations in the isolated rat aorta. AB - Gou-teng is a drug used for treatment of hypertension in Chinese medicine. Its antihypertensive action has been previously confirmed in the spontaneously hypertensive rat (SHR). Here, its vasorelaxing effect and the mechanisms of actions were studied in vitro. Gou-teng extract (GTE) relaxed the norepinephrine (NE)-precontracted aortic ring preparations isolated from Wistar Kyoto rats (WKY) with and without intact endothelium; the latter was significantly less sensitive than the former. The GTE-induced endothelium-dependent relaxation was significantly inhibited by NG-monomethyl-L-arginine (NMMA) in a dose-dependent manner while indomethacin did not affect the relaxation. Atropine inhibited the acetylcholine (ACh)-induced endothelium-dependent relaxation but did not the GTE induced one. Furthermore, once GTE was applied, the following NE-induced contraction was significantly reduced even after repeated washout. NMMA effectively reduced and rather reversed this residual effect of GTE. From these results, it is concluded that GTE relaxes the NE-precontracted rat aorta through endothelium-dependent and, to lesser extent, -independent mechanisms. The endothelium-dependent component would be mediated by EDRF/NO pathway in which the muscarinic cholinoceptors were not involved. Thus, GTE appears to be a potent and long-lasting vasodilator mainly through EDRF/NO release. PMID- 8208066 TI - Mechanism of carbon tetrachloride autoprotection: an in vivo study based on 13C aminopyrine and 13C-galactose breath tests. AB - This study was conducted to evaluate in vivo the hepatotoxic effects of CCl4 administration to rats using 13C breath tests: aminopyrine breath test (ABT) was used to monitor CCl4-induced cytochrome P450 inactivation, and galactose breath test (GBT) to quantitatively measure the CCl4-induced decrease of liver function. The ABT results showed profound aminopyrine demethylation inhibition lasting for three days and complete recovery at day 7, while GBT results were decreased only one day after CCl4. The protection induced by a first CCl4 dose against a second one paralleled cytochrome P450 inactivation: a second CCl4 dose given three days after the first one induced no GBT decrease and a mild increase of serum transaminase activities. On the other hand, the second dose administered 7 days after the first one produced a GBT decrease similar to the one observed after the first one. These results should be taken into consideration to determine the optimal CCl4 dosing schedule in the rat CCl4-induced cirrhosis model. PMID- 8208067 TI - New targets for cancer therapy. PMID- 8208068 TI - Negligent sanitation practices in Baltimore barber shops. PMID- 8208069 TI - Fine-needle aspiration cytologic biopsies. PMID- 8208070 TI - Nursing home medicine in Maryland. AB - Long-term care continues to expand due to demographic, societal, and economic forces, and it is becoming a major factor in the reorganization of health care delivery. Nursing home medicine presents an unusual array of clinical and psychiatric problems, a different working environment, and a different set of administrative regulations. This care setting presents a challenge and an opportunity to the prepared physician. PMID- 8208071 TI - Avoiding polypharmacy and iatrogenesis in the nursing home. AB - The vast majority of nursing home patients over age 65 take at least one prescription medicine, and, on average, seven drugs are concurrently prescribed for each of these patients. One result of this polypharmacy is an increased risk of iatrogenic disease. The authors discuss traditional prescribing patterns in nursing homes and how these patterns contribute to drug-drug and drug-disease interactions in nursing home patients, as well as strategies to reduce polypharmacy and iatrogenesis. PMID- 8208072 TI - Delirium. AB - Delirium, a common psychiatric disorder in the elderly, can be difficult to identify. This article describes the two central features of delirium: diminished cognitive capacity and altered levels of consciousness. Treatment and research into the mechanisms of delirium are discussed. PMID- 8208073 TI - The management of urinary incontinence in the long-term patient. AB - Urinary incontinence affects 50%-80% of residents in nursing homes, presenting a challenge to the health care team. Assessment of urinary incontinence is crucial to selecting appropriate treatment. This article addresses the scope of the problem, incontinence assessment, and treatment specific to nursing home residents. PMID- 8208075 TI - Fever in the nursing home resident. AB - Body temperature is a convenient and objective indicator of the body's physiologic state. Typical and atypical febrile responses are discussed and their sources reviewed. Diagnosis, treatment, and prevention of fever in nursing home patients are highlighted. PMID- 8208076 TI - The wound unit: a specialized unit for pressure sore management in a long-term care facility. AB - Approximately 20% of all patients admitted to long-term care facilities arrive with pressure sores. An additional 12% develop new sores over each subsequent six month period. Management of pressure sores has traditionally been a time consuming, inefficient, and costly exercise. We describe the efforts to standardize and improve the care of patients with pressure sores at a 360-bed chronic care and nursing facility in Maryland. The efforts began with a pressure ulcer team, and continued with the establishment of a wound protocol and, ultimately, a wound unit. PMID- 8208074 TI - The restraint-free approach to behavior problems in the nursing home. AB - The Omnibus Budget Reconciliation Act of 1987 states that nursing home residents have the right to be free of physical and chemical restraints that are not required to treat the residents' medical symptoms. The article outlines a "restraint proper" approach to treating behavior problems: assess the problem, establish a presumptive diagnosis, consider the risks and benefits of treatment alternatives, select the best treatment for the individual patient, evaluate the effectiveness of treatment and side effects, change treatment as necessary, discontinue treatments when they are no longer needed, and provide documentation. PMID- 8208077 TI - Summary of the NIH consensus statement on early identification of hearing impairment in infants and young children. PMID- 8208078 TI - Selecting the appropriate method and time for a hearing impairment screen: is the NIH consensus statement premature? PMID- 8208079 TI - Med Chi library moving toward the year 2000: online information sharing is the key. PMID- 8208080 TI - President Clinton's health system reform plan: is this what we want? PMID- 8208081 TI - [Filing and processing systems of ultrasonic images in personal computers]. AB - The paper covers the software pattern for the ultrasonic image filing and processing system. The system records images on a computer display in real time or still, processes them by local filtration techniques, makes different measurements and stores the findings in the graphic database. It is stressed that the database should be implemented as a network version. PMID- 8208082 TI - [A single card computer used in manufacturing medical devices]. AB - The paper outlines the construction of a unicard built-in computer used as a controlling and computing block in intricate medical devices and discusses the specific use of the computer and its place among other universal computers. PMID- 8208083 TI - [Stereometric model of respiration with diaphragm electrostimulation]. AB - A stereometric model of respiration has been proposed, which is based on the approximation of the surface of the chest and that of the diaphragm by the well known mathematical functions, which generally calculates the value of respiratory volume as a function of geometric parameters such as the circumference of the chest and torso, the distance between the thoracic vertebrae. The derived formulas may be used as a background material for designing the feedback systems by the respiratory volume in order to maximally approach the electrically stimulated respiration to physiological respiration. PMID- 8208084 TI - [Use of spheric micro lens elements for laser angioplasty]. AB - The molding of laser energy by spherical microlens fiber tips applied to laser angioplasty has been experimentally calculated and investigated. The Monte-Carlo method has been proposed to simplify a calculation procedure. This has reduced the necessary amount of test light rays (250 versus 2100 in the former studies). A simplified calculation model (bicentric) is given, which replaces the Monte Carlo method in many practical cases. The calculation data are in a good agreement with experimental findings. PMID- 8208085 TI - [Instrumental and programmed support for integration of diagnostic information within the local network]. AB - The paper deals with the problems in the integration of diagnostic information obtained by various devices, suggests that this process should be implemented by local networks, considers the basic tasks arising with this approach, and gives how to solve some of them. It is shown that this approach can be applied when two basic subdivisions of a health institution: therapeutical and diagnostical- interact. PMID- 8208086 TI - [Example of organizing a middle-size business in medical industry]. AB - The paper deals with the organization of activities of a joint venture in diagnostic medical equipment under the conditions of arising market relations in Russia. A block diagram of the enterprise is proposed, which ensures rather effective research, production, and commerce activities. The tasks facing a marketing sector are given in detail. PMID- 8208087 TI - [Current computerized systems for automatic analysis of electric cardiac signals]. AB - The paper discusses the trend in developing the cardiosystems used at multidisciplinary therapeutical-and-prophylactic institutions, shows the evergrowing role of personal computers to expand the functional potentials of the cardiological systems, and considers the basic requirements for soft- and hardware. PMID- 8208088 TI - [Effectiveness of detection and stimulation of myocardium with titanium electrodes coated with titanium nitride]. PMID- 8208089 TI - [Experience with the use of Doppler ultrasonographic devices at the functional diagnosis department]. AB - The paper discusses the results of 4-year use of Doppler ultrasonographic devices of the Angiodop-2 family at the functional diagnosis unit of a large-scale multidisciplinary hospital, considers the basic disadvantages revealed during their operation. A two-stage scheme for examination of angiological patients by using various technical aids for assessing the velocity of blood flow is presented. PMID- 8208090 TI - [A medical valve]. PMID- 8208091 TI - [Apparatus for ultrasound therapy 1.08 F]. AB - The paper considers the specifications of the apparatus for ultrasound therapy with the use of microprocessor control. PMID- 8208092 TI - [Medical gels for ultrasonographic diagnosis, therapy and electrocardiography]. AB - The All-Russian Research Institute of Medical Polymers has designed the medical gels REPAC, DIAGEL, for ultrasound diagnosis, REPAC-T for ultrasound therapy, ELCON and ELCARD for electrocardiography. REPAC, DIAGEL, and REPAC-T have the least sound damping factor (approximately 10(-3) dB/cm) as compared to other similar gels. REPAC and DIAGEL showed a good performance when they were applied in clinical practice during a year. REPAC-T is the gel that can be used both for ultrasound studies and for ultrasound therapy. Unlike REPAC, it has a longer drying-out time, ensuring a 100% contact between the patient's body and the transducer up to 20 minutes. Other gels have been designed for long-term ECG monitoring, bicycle ergometry, etc. ELCARD and ELCON have conductivities of 0.4 0.6 and 0.6-0.9 ohm/m, respectively. PMID- 8208093 TI - [Pulse oximeter OXIPULSE-01]. PMID- 8208094 TI - [Development and use of antitubercular biocompatible implants for the treatment of tuberculous spondylitis]. AB - The paper deals with the experimental and clinical study of a new implantable therapeutical means based on biocompatible implants containing the antituberculous agent benemycin. The developed implantant having 4 coatings releases within 10 days as high as 37% of the applied drug benemycin. Then within further 30-70 days, release of the drug is 0.7% a day. The parallel bacteriological studies with the operative material placed in agar made 30-60 days after surgery have indicated that growth retardment in rabbits is 17-30 mm, which corresponds to the levels of rifandin (0.125-1.0 microgram/g tissue. The developed implantant has been used in 130 cases of the surgical treatment of tuberculous spondylitis in order to replace a defect of the body of a vertebra and to make a depot for the antituberculous drug just in the focus. Formation of the pulley at the site of intervention was noted in 57 (43.8%) cases within 5 months and in 62 (47.7%) cases within 10 months. The developed implantant has no toxicity and produces no allergic reactions. The position results of the treatment allows it to be recommended for use in clinical practice. PMID- 8208095 TI - [Disposable polymer products for artificial cleansing of blood]. AB - During artificial blood clearance, disposable articles are used for extracorporeal transportation of physiological fluids under sterile conditions and for normalizing action on blood in the acting elements of artificial organs. They allow improvement of clinical parameters, safety and accessibility of the technique of extracorporeal life support. A universal kit of arteries is proposed for artificial clearance. PMID- 8208096 TI - [Interaction of heparinized polymer materials with plasma proteins and thrombocytes]. AB - The interaction of heparinized polymer materials with human plasma proteins (serum albumin (SA), fibrinogen (F), antithrombin III (AT-III)) and platelets was studied. The level of SA and F adsorption irreversibility was demonstrated to depend on the mode of heparin immobilization. There was a negative correlation between the parameters of protein adsorption and the level of adsorbed AT-III. The relationship of the count of platelets adhered to the surface of heparinized polymer materials, to the time of contact was shown to be extreme. There was a correlation between the count of adhesive platelets and the parameters of plasma protein and AT-III adsorption. Based on experimental evidence, a scheme was proposed, which describes the impact of protein adsorption processes on the anticoagulative activity of surface-bound heparin, It is concluded that AT-III plays a particular role as the major component of the adsorption layer that is responsible for the nature of interactions of polymer materials with blood at the protein and cellular levels. PMID- 8208097 TI - [Polymer biodegradable therapeutic films- an effective dosage form for systemic and topical therapy]. AB - The paper describes the property and functional advantages of therapeutical agents of various use as therapeutical films wherein polymer matrix bases providing the prolonged action of drugs are employed. PMID- 8208098 TI - [Polymer biodegradable peptide films. Preliminary results of use of thyroliberin films in substance abuse treatment and psychiatry]. AB - The paper contains data on the new highly effective agent thyropol which is a film from biocompatible copolymers with the immobilized peptide agent thyroid releasing hormone, which has pronounced antialcoholic and psychotropic activities. PMID- 8208099 TI - [Drainage instruments made of polymers]. AB - The paper describes the drainage systems developed by the Medinstrument Research Production Association, such as nephropyelostomic catheters, drainage tubes of the Saratoga type, surgical aspiration instruments (tips) made of flexible medical PVC of various modifications. Their testing in the leading clinics of the Russian Federation has shown that the instruments will find a wide application in urological and surgical units. Their use will take some burden from medical personnel and have its therapeutical, social, and economic impact. PMID- 8208100 TI - [The main fields of application and trends in the development of polymer devices for medical use]. PMID- 8208101 TI - [Kapromed - antibacterial suture material]. AB - The paper gives data on the composition and strength characteristics and experimental and clinical findings of resolving antimicrobial suture materials, such as Capromed-type one, based on the modified caproic fiber coated by the biocompatible polymer PPB-1 which contains antimicrobial drugs. Capromed threads are demonstrated to have high strength characteristics and resolve in the body within 8-9 months. Coating the modified caproic fibers with the biocompatible copolymer imparts them pseudomonfilament characteristics and prevents the penetration of cellular elements to the thickness of threads. The content of antibacterial agents in the polymer coating confers prolonged antibacterial properties on Capromed. Desorption of antimicrobial agents from Capromed is conducive to more favourable healing, prevents the development of ligature fistulas, favours an over 4-fold reduction in the incidence of wound complications, as compared to the controls. PMID- 8208102 TI - [Ocular therapeutic films: long-term results and perspectives of use]. PMID- 8208103 TI - [Polymer biocompatible X-ray contract hydrogel for esophageal vein obstruction in portal hypertension]. PMID- 8208104 TI - [Use of biocompatible soluble polymers in reconstructive surgery]. AB - The paper provides the functional characteristics and results of clinical application of implants based on N-vinylpyrrolidone-butylmethacrylate copolymer to eliminate mandibular bone defect. The implants are indicated to ensure reliable fixation and promote the formation of a valuable osseous regenerate due to their capacity to self-resolve and osteoconductivity. The application of the N vinylpyrrolidone-butylmethacrylate copolymer-based implants substantially widens the scope of reconstructive surgery. PMID- 8208105 TI - [Economic effectiveness of the use of ocular therapeutic films in veterinary ophthalmology]. PMID- 8208106 TI - [Antimicrobial soluble polymers in prevention of postoperative complications in abdominal surgery]. PMID- 8208107 TI - [Set of microsurgical instruments for ophthalmologic plastic surgery]. PMID- 8208108 TI - [BOP-polymer implants for fixation of tubular bones and replacement of osseous tissue defects]. AB - The paper provides the functional characteristics of and clinical findings of the employment of 4 pins for osteosynthesis from biocompatible polymers and shows that the pins ensure reliable fixation of bone fragments and due to their ability to resolve in the body they require no repeated operations for their extraction. The application of the polymer pins substantially widens the scopes for reconstructive operations, enables additional fixation to eliminate rotor mobility, additional fixation of bone fragments, allowing for combined osteosynthesis in fractures of the upper and lower thirds of bones. The employment of antimicrobial pins allows one to prevent postoperative suppurations in open fractures and to treat osteomyelitis. The developed material to fill bone defects with PPV ensures a rapid filling of osseous cavilities with its intrinsic osseous regenerates, recovery of normal osseous tissue in Perthes' disease, and fixation of endoprostheses. The author presents a procedure for applying a kit for replacement of skull defects and indicates that the material substitutes defects of various outlines and rapidly restores the strength characteristics of the skull. PMID- 8208109 TI - Time and frequency domain analysis of NMR data compared: an application to 1D 1H spectra of lipoproteins. AB - A comparison between a time domain analysis algorithm (VARPRO) and a frequency domain analysis algorithm (FITPLAC) for parameter estimation of magnetic resonance spectroscopy (MRS) data series is presented. VARPRO analyses the measured MRS signal (free induction decay; FID); FITPLAC analyses the discrete Fourier transform of the FID, the frequency domain magnetic resonance spectrum. A rapid time domain method, used to subtract the dominating water resonance from a 1H MRS FID, without affecting the metabolites of interest, is outlined and applied. Also a new "pseudofrequency selective" approach to time domain fitting is introduced. The possibilities of combining the most favorable features of time and frequency domain processing into one single MRS signal processing method are assessed. The 1H MRS signals of ultracentrifuged very low (VLDL), intermediate (IDL), and high (HDL) density lipoprotein fractions from human blood plasma were used for the comparisons. The results from both algorithms were in good agreement. PMID- 8208110 TI - Water and fat MR imaging with chemical shift selective 3D steady state methods. AB - A new 3D acquisition regimen that enables the collection of conventional, water suppressed, and fat-suppressed images with no increase in scan times compared with currently implemented 3D sequences is presented. The method is based on conventional 3D steady state with interleaved selective excitation of the fat resonance resulting in acquisition of a fat-based image during the TR period experienced by the water spins. This new sequence is relatively tolerant to susceptibility artifacts and results in excellent water-based images. Because the idea, which we propose, is independent of the type of steady-state imaging protocol utilized, it can be easily applied with regimens that are specifically tailored to enhance contrast. PMID- 8208111 TI - Automated single-voxel proton MRS: technical development and multisite verification. AB - To improve clinical utility, an integrated method has been developed to automatically acquire and process single-voxel in vivo proton spectra on a 1.5 T clinical scanner. This method includes automated adjustment of linear shims using a very rapid modified simplex method, automated water suppression, and applies a water referencing scheme to correct for phase and residual eddy current effects. No operator intervention is required for the acquisition and processing of these pure-absorption spectra. This method was tested in a preliminary multisite trial to determine intersite and intrasite variability of metabolite ratio measurements. In a sample of over 100 examinations, the standard deviation of the ratios NAA:Cr, Cho:Cr, and ml:Cr were found to be under 15% when using this method, a substantially narrower range than has been found in studies relying on manual adjustment of the instrument and/or manual processing. This result indicates that automated setting of acquisition and processing parameters is of critical importance in the clinical application of in vivo spectroscopy. PMID- 8208112 TI - 13C isotopomer analyses in intact tissue using [13C]homonuclear decoupling. AB - Entry of 13C-enriched acetyl-CoA into the citric acid cycle results in scrambling of 13C into the various carbon positions of all intermediate pools. The eventual result is that the 13C resonances of all detectable intermediates or molecules exchanging with those intermediates appear as multiplets due to nearest neighbor spin-spin couplings. We have previously shown that an isotopomer analysis of the glutamate 13C multiplets provides a history of 13C flow through the cycle pools and that relative substrate utilization and relative anaplerotic flux can be quantitated (C.R. Malloy, A.D. Sherry, and F.M.H. Jeffrey, Am. J. Physiol. 259, H987-H995 (1990)). A major limitation of the method for in vivo applications is spectral resolution of multiline resonances required for a complete isotopomer analysis. We now show that [13C]homonuclear decoupling of the glutamate C3 resonance collapses nine-line C4 and C2 resonances into three-line multiplets. We demonstrate that these three-line 13C multiplets are well resolved in isolated, perfused rat hearts and present steady-state equations that allow an isotopomer analysis from data obtained in intact tissue. This advancement offers for the first time the possibility of extending 13C isotopomer methods to complex metabolic conditions in vivo. PMID- 8208113 TI - Phantom studies simulating the impact of trabecular structure on marrow relaxation time, T2'. AB - Phantom studies were conducted to investigate the impact of trabecular structure on the T2' signal measured by MRI. For a separation of density from structural effects, several phantoms were built. They consisted of parallel polyethylene strings arranged in a variety of different patterns to simulate a) a constant uniform trabecular distribution with increasing trabecular thickness and b) different structures with identical overall trabecular density. An asymmetric spin echo sequence was used to determine the apparent relaxation time T2'. Changes in T2' are induced by susceptibility differences between the polyethylene strings simulating trabeculae and Gd-DTPA doped saline simulating bone marrow. The results showed an increasing T2' decay rate with a) decreasing spacing while the string density was constant and b) with increasing string density while the string arrangement was constant. The results demonstrate that the T2' signal is affected not only by density but also by spatial distribution. However, the results also indicate that a separation of the two effects is not possible from a T2' measurement alone, but that e.g., a matching CT slice that would provide purely density information is additionally needed. Theoretical simulations confirmed these results. PMID- 8208114 TI - Gd-DOTA as a gastrointestinal contrast agent for gastric emptying measurements with MRI. AB - Current MR meal markers may interfere with gastric motility and secretion restricting the use of MRI in the measurement of gastric physiology. We therefore evaluated Gd-DOTA as a liquid phase marker, in vitro by determining dissociation, and adherence to the solids, and in vivo by simultaneous MRI (0.35 T scanner, multiple T1-weighted sections of the upper abdomen) and double indicator (perfusion marker PEG 4000, meal marker 99mTc-DTPA) measurements of emptying and secretion, following ingestion of 500 ml 10% glucose. In vitro Gd-DOTA was stable at a pH > 2 with < 2% dissociation at 24 h during incubation with HCl. Dissociation during incubation with HCl was linearly dependent on H+ concentration (0.77 < pH < 2.02). Less Gd-DOTA was absorbed onto the solid phase than 99mTc-DTPA (25% cf 36%). In vivo Gd-DOTA marked gastric contents provided strong positive contrast. Similar emptying curves were observed with both MRI and double-indicator techniques (r = 0.987, P < 0.001). Gd-DOTA has the potential to be a useful liquid phase contrast agent in MR studies on gastric function. PMID- 8208115 TI - Determinants of anisotropic water diffusion in nerves. AB - We report NMR diffusion measurements of water in three central nervous system models, namely the nonmyelinated olfactory, and the myelinated trigeminal and optic nerves of the spotted and long-nosed garfish. A similar degree of anisotropy of the average diffusion coefficients (DNMR) is observed for all three freshly excised nerve types (DNMR(parallel)/DNMR-(perpendicular) is 3.6 +/- 1.2, 3.2 +/- 0.9, and 2.6 +/- 0.4 for the olfactory, trigeminal, and optic nerves, respectively). The anisotropy of DNMR for the nonmyelinated olfactory nerve argues strongly that myelin is not a necessary determinant of diffusional anisotropy in ordered axonal systems (even though it may contribute when present). Garfish nerves treated with vinblastine, in order to depolymerize microtubules and inhibit fast axonal transport, also exhibit diffusional anisotropy (DNMR(parallel)/DNMR(perpendicular) is 2.6 +/- 0.4, 2.8 +/- 0.8, and 2.2 +/- 0.7 for the olfactory, trigeminal, and optic nerves, respectively) thus excluding a significant role for microtubules and fast axonal transport in that observed anisotropy. PMID- 8208116 TI - True myocardial motion tracking. AB - Myocardial tagging is a powerful tool for the assessment of in-plane cardiac motion. However, for previous myocardial tagging techniques, the imaged slice is fixed with respect to the magnet coordinate system. Thus, images acquired at different heart phases do not always represent the same slice of the myocardium. A new myocardial tagging technique is presented, which takes the through-plane motion into consideration. It involves tagging of the desired myocardial slice and applying a subtraction imaging technique to image just that part of the myocardium. The examination time can be reduced considerably by the acquisition of two one-dimensionally tagged images. To increase the signal-to-noise ratio especially at later heart phases, variable imaging RF excitation flip angles are applied. To reduce motion artifacts a repetitive breathhold scheme was applied. In vivo results demonstrate that the tags can be accurately tracked within the entire heart period with a temporal resolution of 35 ms, even at a top basal level of the heart and right ventricle. PMID- 8208117 TI - Three-dimensional time-of-flight MR angiography using selective inversion recovery RAGE with fat saturation and ECG-triggering: application to renal arteries. AB - A three-dimensional (3D), ECG-triggered, selective inversion recovery (SIR) rapid gradient-echo (RAGE) technique is proposed to obtain MR angiograms of the main renal arteries. By using the selective inversion recovery and fat saturation, the background is significantly suppressed while blood maintains a high signal intensity as compared with conventional 3D time-of-flight (TOF) MR angiography. The sequence is ECG-triggered so that blood in-flow is maximized during systole, and intravoxel dephasing and pulsatile flow artifacts are minimized by collecting data during diastole. As a result, vessel boundary blurring and ghosting artifacts due to background motion are dramatically reduced, and the conspicuity and lumen definition of the arteries are significantly improved. High-quality MR angiograms of the main renal arteries with excellent blood/tissue contrast and suppression of motion artifacts have been consistently obtained for normal volunteers, with the length of visualization being 51 +/- 07 mm for the left, and 57 +/- 06 mm for the right renal arteries, significantly greater than using conventional 3D TOF pulse sequences. Statistical analysis was performed by using a one-sided Student's t test. PMID- 8208118 TI - A microscope slide probe for high resolution imaging at 11.7 Tesla. AB - We present details of a novel RF coil for use in NMR microscopy. This coil is an inductively coupled surface coil which is built into a standard microscope slide. The coil is highly sensitive and is also designed so that the sample to be imaged can be viewed under an optical microscope. This facility allows comparison of optical and NMR micrographs, as well as accurate sample positioning. Using the slide coil, images of onion epidermal cells with an in-plane resolution of 4.5 microns have been produced. PMID- 8208119 TI - Experimental study of the effects of "fractional" gating on flow measurements. AB - Velocity encoded phase imaging is subject to errors from phase and amplitude variations of the k-space data caused by beat-to-beat variations of the flow. Fractional cardiac gating is defined as asynchronous gating with each phase encode step occupying a fixed fraction of the RR interval. The gating fraction is the inverse of the number of phase encode steps taken per RR interval. Studies in normal subjects show that deviations and standard errors of ascending and descending aorta flow measurements are significantly greater with decreased gating fraction. Significant errors occur when gating does not separate systolic and diastolic data. The studies establish a graded trade-off between flow measurement accuracy and precision with imaging time, and show that standard nongated phase contrast measurements of strongly pulsatile flow are unreliable. PMID- 8208120 TI - Stability assessment of gadolinium complexes by P-31 and H-1 relaxometry. AB - Longitudinal P-31 relaxation rate enhancements of phosphate groups have been measured at pH 7-7.2 and 310 degrees K on aqueous solutions containing adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi) and some lanthanide complexes (Gd-DOTA, Gd-HPDO3A, Gd-DO3A, Gd-DTPA, Gd-DTPA-BMA). The macrocyclic complexes induce linear enhancements of the relaxation rates of all phosphorus nuclei. For Gd-DOTA and Gd-HPDO3A, the mechanism of the interaction with the P-31 nuclei seems to be of the outer sphere type and a better efficiency is noted for the "neutral" Gd-HPDO3A. A short-lived ternary complex between Gd DO3A and the phosphorylated metabolites appears to be formed enabling an inner sphere interaction. In solutions containing the open chain complexes, Gd-DTPA and Gd-DTPA-BMA, P-31 relaxation rates of ATP exhibit significant and nonlinear enhancements that are much larger than those observed for PCr and Pi. A ternary complex involving the lanthanide ion, its original chelator, and the ATP molecule is precluded by various experiments which confirm that the lanthanide ion shifts from the original complexes to the ATP phosphate groups. PMID- 8208121 TI - Accurate T1 determination from inversion recovery images: application to human brain at 4 Tesla. AB - It is well known that the signal polarity in inversion-recovery (IR) images changes with inversion time, complicating the determination of T1. To avoid this problem, a simple subtraction method is implemented. In this method, k-space data of the longest inversion time are subtracted from the corresponding data of each inversion time. This subtraction yields IR images of same polarity, making it straightforward to derive T1 using a standard fitting routine. Phantom T1 studies with IR Turbo-FLASH images demonstrate that this technique is robust and accurate. Four Tesla T1 values of the human brain were also determined by this method to demonstrate its in vivo utility. PMID- 8208122 TI - Torque free asymmetric gradient coils for echo planar imaging. AB - In this work, we present a new torque-free asymmetric gradient coil that is capable of generating high quality axial, sagittal, and coronal echo planar images of the human head. This gradient set was calculated using the Biot-Savart law and least square approaches to optimize the field in the region of interest and to minimize net torques. The resulting structure has excellent shoulder-to coil clearance and, as such, has the advantage of providing good patient access to the linear portion of the gradient while minimizing patient discomfort from claustrophobia. PMID- 8208123 TI - Rapid monitoring of changes in water diffusion coefficients during reversible ischemia in cat and rat brain. AB - Changes in the diffusion constant of water during reversible brain ischemia and cardiac arrest were monitored with a 10-s time resolution. Results (five cats, three rats) indicate that these changes are reversible and that the bulk of the changes are not caused by temperature or motion related to brain pulsations and blood flow. The rapid time course of the changes corresponds to the known time course for changes in energy state, signal transduction, and ionic homeostasis. PMID- 8208124 TI - Dual contrast GRASE (gradient-spin echo) imaging using mixed bandwidth. AB - Equal time spacing of RF pulses in the CPMG sequence imposes a constraint of equal signal read periods in spin-echo train imaging. GRASE imaging differs by using multiple read gradients in each pi-pi time interval, which are not constrained to be equal in number or duration. This additional degree of freedom is developed in dual contrast imaging. Closely spaced read periods are used for the PDW image to reduce T2 decay effects, while fewer low-bandwidth read periods in each of several pi-pi intervals are used to raise the signal-to-noise ratio and avoid signal averaging in the T2-weighted image. PMID- 8208125 TI - Mathematical basis of eigenimage filtering. PMID- 8208126 TI - Mitotic indirect non-disjunction in phytohemagglutinin stimulated human lymphocytes. AB - In a previous publication we demonstrated that in cells of Vicia faba micronuclei derived from whole lagging chromosomes or chromatids may perform DNA synthesis and mitotic condensation in synchrony with main nuclei and be regained by main nuclei at the next mitosis, giving rise to trisomic cells together with diploids. This process was called 'mitotic indirect non-disjunction' (MIND). In the present work the occurrence of MIND was studied in human lymphocytes cultivated in vitro. Human lymphocytes were treated with low colcemid concentrations until fixation; BrUdR was supplied together with colcemid to distinguish the number of mitoses performed by the cells (M1, M2 and M3 cells). The frequencies of M1 ana telophases with single lagging chromosomes/chromatids and of M2+ prophases with single micronuclei in synchronous motitic condensation with main nuclei were evaluated. On this basis the expected frequencies of both monosomic and trisomic M2 cells were calculated, according to the hypothesis of MIND. Their observed frequencies were very close to those expected. These results support the hypothesis of the occurrence of MIND in human lymphocytes. PMID- 8208127 TI - Evaluation of pyrazole and ethanol induced S9 fraction in bacterial mutagenicity testing. AB - A major constitutive enzyme in the liver of the uninduced rat is cytochrome P450 2E1. This isozyme has been shown to metabolize a number of carcinogens, including low molecular weight nitrosamines and a number of compounds normally regarded as non-mutagenic in the Ames test, e.g. aniline, urethane and benzene. Using the standard induction procedures [Aroclor 1254 or a combination of phenobarbitone (PB) and beta-naphthoflavone (beta-NF)] the level of CYP2E1 in rat liver is actually suppressed and it has been suggested that this may account for the negative findings with these compounds in the Ames test. S9 fractions were prepared from rats pre-treated with pyrazole or ethanol (inducers of CYP2E1) and then used in the Ames test (or pre-incubation modification) with urethane, acetaminophen, aniline, benzene, procarbazine and N-nitrosopyrrolidine. Both pyrazole and ethanol induced S9 were superior to PB/beta-NF-S9 and uninduced-S9 for the activation of N-nitrosopyrrolidine, a known CYP2E1 substrate. However, there was no evidence of mutagenic activity with urethane, aniline, benzene, procarbazine or acetaminophen. As these compounds have demonstrated genotoxicity in vivo, additional important metabolic pathways must be required which are not present in rat liver S9 fraction. PMID- 8208128 TI - The relationship between DNA content and centromere content in micronucleated mouse bone marrow erythrocytes analysed by flow cytometry and fluorescent in situ hybridization. AB - A fixation method for mouse bone marrow erythrocytes was developed which allows both flow cytometric enumeration of micronucleated polychromatic erythrocytes (MPCEs) and detection of centromeres using fluorescent in situ hybridization (FISH) with a mouse gamma satellite probe on flow-sorted MPCEs. Male CBA mice were treated with clastogens or spindle poisons: X-irradiation (XR; 0.5 Gy), cyclophosphamide (CPA; 80 mg/kg), vincristine sulphate (VCR; 0.125 mg/kg) and colchicine (COL; 1 mg/kg). At 30 and 50 h after treatment bone marrow suspensions were prepared and subsequently analysed by flow cytometry to enumerate and determine the DNA content of induced MPCEs. The mean DNA content in MPCEs was found to be higher after treatments with the two aneugens, VCR and COL, than with the two clastogens, CPA and XR. The mean DNA content of MPCEs was positively correlated with the mean proportion of micronuclei (MN) containing centromeres, indicating that determination of the mean DNA content alone can give information about the mechanism of MN induction. When the MPCEs induced with VCR were outsorted according to four classes of increasing DNA content and the presence or absence of centromeres was determined with FISH, it was found that only the class with the lowest DNA content (0.8-1.7% of the diploid DNA content) had a low proportion (< 20%) of centromere-containing micronuclei while in the three classes with higher DNA content (1.7-10.2% of the diploid DNA content) > 80% of the MN had centromeres. This was in contrast to the results from treatments with CPA where the proportion of centromere-containing MN did not increase with increasing DNA content. PMID- 8208129 TI - Structural basis of antimutagenicity of chemicals towards 4-nitroquinoline 1 oxide in Salmonella typhimurium. AB - Eighty-eight organic compounds representing a variety of chemical classes, a proportion of which possess antimutagenic and/or anticarcinogenic properties, were compared for their ability to inhibit the direct-acting mutagenicity of 4 nitroquinoline 1-oxide (4NQO) in strain TA100 of Salmonella typhimurium. Twelve compounds were found to decrease 4NQO-induced mutagenicity by at least 50%, with an antimutagenic potency varying over a 1225-fold range, corresponding to a 4 4900 molar excess of inhibitor over that of 4NQO. The resulting antimutagenicity data base was subjected to structural analysis by the computer automated structure evaluation (CASE) methodology, which identified one structural determinant (biophore) and four biophobes. The biophore contained the sulfhydryl group, present in three thiols and five aminothiols, all of which inhibited 4NQO mutagenicity. Conversely, the corresponding disulphides or thioethers as well as dithiocarbamates, isothiocyanates and other sulfur-containing compounds were devoid of antimutagenicity towards 4NQO. A distinctive dichotomy in the ability to inhibit 4NQO mutagenicity was observed with pairs of structurally and metabolically related compounds, such as the polyamines spermidine (antimutagenic) versus spermine and the tetrapyrroles bilirubin (antimutagenic) versus biliverdine. Curcumin and myricetin were the only inhibitors of 4NQO induced mutagenicity out of a group of 12 phenols and three bioflavonoids, respectively. One biophobe was an oxidized sulfhydryl moiety, while the other three were derived from benzene or its derivatives. Some of these phenyl compounds are known antioxidants. Thus, nucleophilicity rather than antioxidant properties appears to play a role in antimutagenicity to 4NQO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208130 TI - Detection of nitro-azabenzo[a]pyrene derivatives in the semivolatile phase originating from airborne particulate matter, diesel and gasoline vehicles. AB - Mutagens in the semivolatile phase of airborne particulate matter, diesel and gasoline engine emissions were investigated using chemical and biological assays. The previously unknown mutagens, 1-(3-)nitro-6-azabenzo[a]pyrenes (1-N-6-ABP and 3-N-6-ABP) and 1-(3-)nitro-6-azabenzo[a]pyrene-N-oxides (1-N-6-ABPO and 3-N-6 ABPO), were detected in the semivolatile phase, which was adsorbed onto XAD-4 resin combined with a Teflon-coated fibre filter. Dichloromethane extracts of materials adsorbed onto XAD-4 resin were divided into acidic, neutral and basic by liquid-liquid separation. These chemicals in the basic fraction were the major mutagens in the semivolatile phase when they were bioassayed using Salmonella typhimurium TA98 in the absence of S9 mix; the mutagenicity of the basic fraction contributed at the rate of 42.9-68.8% of that of crude extracts for airborne, diesel and gasoline emission materials. As the mutagens were found to be difficult to analyse by gas chromatography (because of their probable absorption onto the packing) they were purified by HPLC and analysed by mass spectrometry. The concentrations of 1-N-6-ABP, 3-N-6-ABP, 1-N-6-ABPO and 3-N-6-ABPO detected were 1.1, 1.2, 0.8 and 0.3 ng/g, respectively, of materials in the airborne sample, and 4.9, 7.7, 2.2 and 3.8 ng/g, respectively, of materials in the diesel emission. Only 1-N-6-ABP (3.4 ng/g) and 3-N-6-ABP (4.9 ng/g) were detected in the semivolatile phase of the gasoline engine emission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208131 TI - Microsomal metabolism of the food mutagen 2-amino-3,4,8-trimethyl-3H-imidazo[4,5 f]-quinoxaline to mutagenic metabolites. AB - Heterocyclic aromatic amines are formed in the crust of meat during ordinary cooking. These aromatic amines are potent bacterial mutagens and also potent rodent carcinogens. 2-Amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (DiMeIQx) is one of the more abundant heterocyclic aromatic amines, accounting for approximately 20% of the mutagenic material found in cooked meat. DiMeIQx is metabolically activated, by hepatic microsomes from PCB treated rats, to two major and three minor metabolites. One major and one minor metabolite were identified as 2-hydroxyamino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline and 3,4,8-trimethyl-2-nitro-3H-imidazo[4,5-f]quinoxaline, respectively, confirmed by comparison of HPLC retention times, and UV and mass spectra of synthetic standards. Both metabolites were mutagenic in Salmonella typhimurium TA98 without metabolic activation. The other major metabolite was identified as 2-amino-8 hydroxymethyl-3,4-dimethyl-3H-imidazo[4,5-f]quinoxaline by mass and NMR spectral analysis. The two remaining minor metabolites were identified as the 2 hydroxyamino- and 2-nitro- derivatives of 2-amino-8-hydroxymethyl-3,4-dimethyl-3H imidazo]4,5-f]quinoxaline by UV and mass spectral analysis. Both of these metabolites were mutagenic in S. typhimurium TA98 without metabolic activation. PMID- 8208132 TI - Analysis of 4-nitroquinoline-1-oxide induced mutations at the hprt locus in mammalian cells: possible involvement of preferential DNA repair. AB - Mutation spectra induced by 4-nitroquinoline 1-oxide (4NQO) at the hprt locus for both normal (AA8) and 4NQO-sensitive (UV5) Chinese hamster ovary cells were determined to investigate the effect of DNA repair on the nature of induced mutations. The UV5 cell line is three times more sensitive to 4NQO than the AA8 parental cell line. In UV5 cells, the dGuo-N2-AQO adduct, which is considered to be the most toxic and mutagenic adduct in Escherichia coli, is poorly repaired. The molecular nature of 30 hprt mutants isolated from AA8 and 20 isolated from UV5 cells was determined by sequence analysis of in vitro amplified hprt cDNA. Both similarities and differences emerged. In both cell lines we found that (i) 4NQO is basically a base substitution mutagen acting almost exclusively at G residues and (ii) G transversions are prevalent over G transitions in both cell lines, independently from the ability to repair dGuo-N2-AQO. A high proportion (13/25) of splice mutations was observed in AA8 cells, statistically different (P < 0.04, Fisher's exact test) from the incidence of splice mutants in UV5 cells (4/20). In AA8 mutants, all but two of the point mutations were due to lesions localized on the non-transcribed strand, suggesting preferential repair of the transcribed strand. Compared with AA8, the proportion of mutants due to lesions present on the transcribed strand was higher in UV5 cells, as expected if a preferential repair mechanism was impaired in the sensitive cell line. Our data are consistent with the molecular defect in DNA repair recently characterized in UV5. PMID- 8208133 TI - Prediction of rodent carcinogenicity for 44 chemicals: results. AB - Methods by which rodent carcinogenicity can be predicted have been prospectively validated for 40 chemicals evaluated for carcinogenicity by the US National Toxicology Program. It is concluded that a chemical of unknown carcinogenicity can be predicted to be in one of three possible categories--probably carcinogenic, probably non-carcinogenic or of uncertain activity. The last category is unlikely to contain genotoxic trans-species and/or multiple-site carcinogens. The component parameters of such predictions are one or more of several aspects of chemical structure, genotoxicity and rodent toxicity. Each of these parameters requires refinement but all are developed to the point that they can be integrated to make assessment of possible carcinogenicity. Carcinogenicity tends to be overpredicted by this integrated technique, each part of which has already been simulated by computer modelling. Improvements in predictive methodology will flow from three assumptions: (i) that emphasis must be placed equally on the properties of the test chemical and the responses it elicits in tissues for which carcinogenicity is to be predicted, (ii) that the integration of different predictive technique is preferable to the exclusive use of a single technique, and (iii) that the general predictivity of any technique or combination of techniques appears to be limited to < or = 80%, imposed by inadequate knowledge, and uncertainties in the experimental evaluation and classification of carcinogenic responses for diverse chemicals. This last statement does not preclude the attainment of higher accuracy within a congeneric series of chemicals. Foreknowledge of the likely outcome of a rodent carcinogenicity bioassay is now possible and will contribute to the focusing of animal testing resources. PMID- 8208134 TI - Similarity in the molecular profile of mutations induced by UV light in shuttle vector plasmids propagated in mouse and human cells. AB - Shuttle vector plasmids pYZ289 were irradiated with UV and transfected to mouse cells to permit repair of damage, mutation and replication in the cells. The frequency and types of mutations were compared with those of UV-irradiated shuttle vector plasmids pZ189 which were propagated in normal human and xeroderma pigmentosum (XP) patient cells defective in DNA repair. Both shuttle vector plasmids contain a bacterial suppressor tRNA gene supF as a common mutation target. pYZ289 propagated in the mouse cells showed survival and mutation frequency similar to pZ189 propagated in the normal human cells. All single base substitution mutations were induced in dipyrimidine sequences and G:C to A:T transition was most frequently observed (47%) in the mouse cells; however, the frequency was significantly lower than that in the XP cells. The frequency of the base substitution mutations at A:T base pairs was significantly higher in the mouse cells (29%) than in the normal human (12%) and the XP cells (6%). These results show that similar types of mutations are induced by UV in mouse and normal human cells, and that the A:T base pair is relatively more mutable in mouse than in normal human and XP cells. PMID- 8208136 TI - Isolation and characterization of sugar nucleotides from Mycobacterium smegmatis. AB - The cell walls of Mycobacterium smegmatis contained a number of serologically active polysaccharides such as arabinomannan, mannan, and glucan in addition to arabinogalactan. The biosynthetic pathways of these polysaccharides are not well understood. Characterization of the sugar nucleotide pool of M. smegmatis showed the presence of (uridine diphosphate-) UDP-glucose, UDP-galactose, UDP-mannose, UDP-arabinose and UDP-hexuronic acid(s). It is suggested that these compounds may be intermediates in the biosynthesis of a number of mycobacterial polysaccharides. PMID- 8208135 TI - Industrial Genotoxicology Group: novel in vivo genotoxicity assays, Royal Society of Medicine, London, UK, December 1992. PMID- 8208137 TI - Simple bacteriological and thin-layer chromatographic methods for determination of individual drug concentrations treated with penicillin-G in combination with one of the aminoglycosides. AB - For the individual determination of residual drug concentrations in meat when using penicillin-G (PC-G) in combination with one of the aminoglycoside antibiotics, the differentiation of PC-G and the aminoglycoside groups was easily accomplished by incubation of the individual drug with penicillinase (PCase). Each aminoglycoside treated with PCase (50 U/ml) produced a similar clear inhibition zone by the aminoglycoside alone, but PC-G treated with PCase produced no inhibition zone even when a high concentration of 100 microg/ml of PC-G was used on the assay plates seeded with Bacillus subtilis or Micrococcus luteus. Furthermore, these drugs could be distinguished and identified according to their characteristic Rf values and colours by the TLC method using silica-gel 60 F254 plates followed by spraying with various chemical reagents. A solution of n butanol:acetic acid:water:p-toluenesulphonic acid (3:1:1:0.7) was the best developing solvent for the separation of all the antibiotics. PMID- 8208138 TI - Changes in translational accuracy of Escherichia coli when folate metabolism is perturbed. AB - Translational accuracy was monitored in Escherichia coli mutants which contain abnormal folate pools. A decrease in translational accuracy was indicated by the increased production of a T4 phage mutant containing a UGA mutation in a tail fibre gene. An E. coli folC mutant suppressed the phage mutant under conditions where it presumably accumulated methyl-tetrahydrofolate (methyl-THF). A UGA suppressor strain with the mutation affecting the primary structure of the tRNA(trp) normally suppressed the phage mutant. When the strain was made thymine requiring it no longer suppressed. The accumulation of methyl-THF which permits suppression by thymine-requiring strains may act to interfere with suppression by the tRNA suppressor, possibly by changing the modification pattern of the tRNA. PMID- 8208140 TI - Evaluation of the diagnostic accuracy of a kit for the rapid detection of group A streptococci. AB - A rapid immunoassay method using an Event Test Strip Strep A experimental kit (Boehringer Mannheim) was evaluated. Results obtained were compared with culture results to evaluate the accuracy of detection of group A streptococci directly from throat swabs or from artificial swabs containing various bacterial concentrations. A good diagnostic accuracy was obtained with a sensitivity of 96.9% in the assay of throat swabs which provided more than ten group A Streptococcus colonies per plate. Since a low level of micro-organisms may indicate infection, it is recommended that a culture be performed when the rapid test based on antigen detection is negative. PMID- 8208139 TI - Biochemical properties of the major outer membrane proteins of Porphyromonas gingivalis. AB - The major outer membrane proteins (MOMP) of 53 and 67 kDa were identified by sodium dodecyl sulphate-polyacrylamide gel electrophoresis in outer membrane enriched fractions of Porphyromonas gingivalis FDC 381 and ATCC 33277, respectively. The MOMP were purified by anion exchange and gel filtration chromatography after extraction with Zwittergent 3-14. Their reactivity to monoclonal antibodies and their amino acid composition were analysed. The N terminal amino acid sequences of twenty residues of both purified MOMP were determined and compared with those previously reported for MOMP of other periodontopathic bacteria. PMID- 8208141 TI - Medical education worldwide. A global strategy for medical education: partners in reform. AB - The on rush of beneficial change which now flows in medical education has never been stronger since the start of this century. Such activity has not been seen since the era of Flexner. There can be no doubt that the world scene is now set for decisive, effective action. The many tributaries of the stream of reform converge this year at Edinburgh, to diverge again into six Regional Conferences during 1994 in Africa, the Americas, the Eastern Mediterranean, Europe, South East Asia and the Western Pacific. The centres of activity and connection cited below do not in any way make up a comprehensive catalogue. Rather, each development and each reform is a link in a chain, a module with which the World Federation for Medical Education (WFME) has been implicated. Each name given, each title stated, is intended as a marker, a nexus. These are among the partners to be mobilized and brought together for the task. PMID- 8208142 TI - Geriatric medicine: does teaching alter medical students' attitudes to elderly people? AB - The development of a questionnaire to assess the attitudes of medical students towards old people is described. Principal components analysis of the responses of 114 first-year medical students revealed two orthogonal factors, named negative attitudes and medical intervention. Scores on these factors were compared among three groups of medical students: first-year students, 64 clinical phase medical students prior to a geriatric medicine course, and 69 medical students who had completed a geriatric medicine course. Negative attitudes scores did not differ between first year and the clinical years, but were reduced after the geriatric medicine course. Scores on the medical intervention factor reduced significantly from first year to the clinical years and were not reduced further by the geriatric medicine course. Women tended to have lower scores on negative attitudes. Medical students appeared to change their attitudes concerning the degree to which medical intervention is appropriate as a result of preclinical or general medical experience. However, their reservations concerning the reward to be gained from working with elderly people were stable over the same periods, but were altered by a course in geriatric medicine. PMID- 8208143 TI - Health education poster: a teaching model for clinical medical students. AB - The teaching of health education or health promotion to medical students is often difficult because they have little experience on which to base their learning. They have limited clinical knowledge and in particular their awareness of the value of and the opportunities for health promotion in general practice is limited. The problem-oriented teaching method described here attempts to make the subject interesting and relevant by asking students, while in their practice attachments, to identify areas of need for health promotion or health education and then to prepare a poster, with supportive background and research, to satisfy that need for display in their given practice. PMID- 8208144 TI - Environmental medicine: its introduction into a medical school primary care requirement. AB - One hundred and twelve medical students participating in a required 6-week primary-care rotation completed a pretest of environmental medicine knowledge and attitudes at the start of the rotation and a similar posttest on the last day of the rotation. Control group students were to participate in the usual weekly didactic sessions of the clerkship. Intervention students were given a booklet describing environmental considerations in clinical medicine and introducing them to the concept of risk assessment, three computer-assisted instruction cases, and a problem-based learning (PBL) exercise involving role-play. Because voluntary compliance with evaluation forms was poor during year one, during the second year students in the intervention group were required to return evaluation forms in order to sit for the course final examination. Knowledge and attitudes of both intervention and control groups were compared at baseline and at the end of the rotation. Students in the intervention group also completed process evaluations of the intervention materials. Students in both intervention and control groups increased knowledge gains significantly during the second year of the intervention, while neither group improved during year 1. This may have been due to a 'spill-over' effect among primary-care teachers implementing the intervention. Students ranked both environmental and occupational medicine of least importance in their training compared with eight other aspects of medicine, and this ranking did not improve with intervention. The PBL exercise was well received by the students. Of 28 evaluations, 27 ranked the session in the highest 3 of a 5-part Likert scale for worthwhile content, and 24 would recommend the session to a friend.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208145 TI - Clinical electives: setting up an overseas programme in a new medical school. AB - This paper describes the methods used to establish an overseas elective programme in a new medical school, the objectives and the perceived results. The aims and objectives of the programme are listed. The students who participated in the programme were from the charter class and had completed the second year of a 3 year clinical programme. The methods used to establish the programme are described. Destinations were organized through academic staff contacts. Systematic preparation of students was an important feature of the programme. Comparative costs and methods of financing the programme are described in detail. The results of the programme are analysed together with the form of assessment used and feedback from both the host institution and the student. The importance of monitoring progress while students are abroad is described. The discussion focuses on the benefits derived from an overseas elective programme for both students and teachers. The advantages and disadvantages of different destinations are compared. Further refinements to the programme are discussed including alternative methods of obtaining funding. The importance of developing reciprocal arrangements with other medical schools and institutions throughout the world is emphasized. PMID- 8208146 TI - Foundations of problem-based learning: some explanatory notes. AB - The present article elaborates on cognitive effects of problem-based learning put forward by Schmidt, De Volder, De Grave, Moust & Patel (1989) and Norman & Schmidt (1992). Its purpose is to discuss, in some detail, the theoretical premises of this approach to learning and instruction. It is argued that problem based learning, above all, promotes the activation of prior knowledge and its elaboration. Evidence is reviewed demonstrating that these processes actually occur in small-group tutorials and that the processing of new information is indeed facilitated by discussion of a relevant problem. These effects must be attributed to a reorganization taking place in the knowledge structures of students as a result of problem-oriented study. In addition, a cognitive process called epistemic curiosity (or intrinsic interest) is enabled. Some directions for further research are outlined. The contribution starts, however, with a discussion of the philosophical and pedagogical roots of problem-based learning. PMID- 8208147 TI - The oral examination: a study of academic and non-academic factors. AB - The oral examination in psychiatry for final-year medical students at Wellington and Dunedin School of Medicine, University of Otago, was studied. Between December 1989 and April 1990, 40 medical students were videorecorded during such an examination. The transcripts of the recording of each oral, and at a later date the videorecordings, were individually scored by a panel of six research psychiatrists who were experienced examiners. In addition verbal and non-verbal behaviour was rated using visual analogue scales and the students completed personality and anxiety questionnaires. There was a low level of agreement between research psychiatrists in the allocation of oral marks. The oral score was positively associated with the level of confidence of the student and negatively with anxiety in men. PMID- 8208148 TI - More women enter medicine: young doctors' family origin and career choice. AB - This study is part of the Finnish Junior Physicians 88 Study, the purpose of which was to shed light on the life situation, career choice and future plans of young doctors and their views on medical education. The survey population included all the medical doctors registered during the years 1977-1986 in Finland (n = 5208). A postal questionnaire was sent to a sample of 2632 doctors born on odd-numbered days. After a reminder letter, 1745 questionnaires (66%) were returned. Forty-nine per cent of the respondents were women. Typically both men and women doctors had a father who was an upper-level white-collar worker and a mother who was a housewife. More men than women had a father who was a doctor or other health professional. More women than men mentioned that a lifelong calling (42% vs 30%), success at school (58% vs 47%) and an interest in helping people (78% vs 71%) had considerable influence on their decision to become a doctor. Men more often than women emphasized the medical profession being regarded as a highly paid (56% vs 47%) and a high status profession (64% vs 56%) and also that a family member was a doctor (15% vs 11%). PMID- 8208149 TI - Specialty choice: development of a questionnaire. AB - Determination of factors which influence medical students' choice of a specialty is potentially important for decisions regarding medical school curricular changes that might influence students' specialty choice. Beginning in 1988, we developed and annually revised a specialty choice questionnaire which was administered to the senior class at the Medical College of Georgia School of Medicine from 1988 to 1991. This paper presents reliability and validity data regarding the questionnaire. Validation procedures involved driving a multiple discriminant function to determine the significance of relationships between a variable and choice of a primary care (PC) or non-primary care (NPC) specialty. Structure coefficients for the multiple discriminant functions that were statistically and practically significant were desire for longitudinal patient care opportunities and desire for monetary rewards. Estimates of internal consistency were derived using Cronbach's alpha. Cronbach's alpha coefficients for this item set were 0.71, 0.59 and 0.46 for 1988, 1989 and 1990 respectively. Test-retest coefficients for the 1991 12-item questionnaire ranged from 0.51 to 0.81. PMID- 8208150 TI - Who are the providers of postgraduate medical education? AB - The view, background and motivation of providers of medical education was studied using a structured questionnaire which was sent to all those who organized courses for the Postgraduate Education Allowance in the West of Scotland. Two hundred and twenty-five replies were received from 254 course providers, giving an 88.6% response rate; 51.8% of course providers were general practitioners, 24.1% hospital consultants, 2% were from the pharmaceutical industry, 3.6% from commercial companies, 2.6% health board administrators, 1% general practitioners also running commercial companies, 14.9% others. Only 29.3% had training for organizing courses, although 68.7% thought special training was important. 43% used a combination of GPs and hospital consultants at their courses and a considerable number continued to organize lecture style courses. 32.8% used pre course material and 50.7% used post-course assessment. 21.5% of providers had to provide their own secretarial back-up. The provision of continuing medical education is haphazard. The new contract has increased the amount of education available without addressing the needs of the providers. Proper training, planning and evaluation of courses, adequate funding, protected time and good secretarial back-up are required for good, meaningful and relevant continuing medical education. PMID- 8208151 TI - Writing a scientific paper as part of the medical curriculum. AB - The curriculum at the Medical School, University of Tromso reserves 23 weeks for optional studies, including a period of 12 weeks at the end of the fifth year when the students carry out an independent study and write a short thesis. Of the first 417 doctors (graduation year 1979-89) from Tromso 84.6% answered a postal questionnaire asking them to evaluate this part of the curriculum. These postgraduates report high levels of satisfaction with and benefit from this part of the curriculum. A total of 26.8% started working on their thesis before the final 12-week period, 32.6% had also published their study, half of these in international journals, and 75.6% found that the skills acquired during the final optional period had been useful in their subsequent work, irrespective of specialty. In conclusion, postgraduates consider their work in preparing a scientific paper as an important and integral part of medical studies. PMID- 8208152 TI - Instructions in learning skills: an integrated approach. AB - The transition from school to university education and a medical school environment can be difficult even for the very best students. However, little appears to be done to assist students in making this transition and in developing study skills during the early stages of their training. This article outlines a scheme which has been called supplemental instruction. Although developed for medical students in the United States, it is particularly well suited to developing essential study skills in first-year medical students in the United Kingdom. The scheme has been successfully introduced into some degree and diploma subjects in this country, with improvement in course grades and lower attrition rates, but has yet to be introduced into medical education. Evaluation data for non-medical courses show that student participation in supplemental instruction significantly improves overall course marks and could be of significant value in the medical curriculum. PMID- 8208153 TI - Non-verbal communication: evaluation of a computer-assisted learning package. AB - A computer-assisted learning (CAL) package was developed on non-verbal communication. Its effectiveness was evaluated by comparing learning based on use of the package with that based on a didactic lecture covering the same topic. A class of 151 first-year medical students was divided into two groups, balanced for gender and home/overseas students. One group was asked to use the CAL package, the other group attended the lecture. Knowledge was assessed one week later by a written test, and reactions to using the CAL package were obtained via a questionnaire. Each group was then allowed and encouraged to use the other resource and then asked about their preferences for type of resource at the end of term. Mean score on the knowledge test was reliably better in the CAL group. In addition, scores increased as the time spent using the CAL package increased: this relationship was highly significant. Use of the CAL package varied from 15 to 120 minutes (median 45). Users reported that it was easy to operate, was an adequate or good resource for learning about the subject, and was a good or reasonable use of their time. After using both types of learning resource half the students judged the CAL package more useful for learning about the subject, and half preferred it to the lecture (the other half had the opposite judgement and preference). This study provides evidence that a CAL package can effectively substitute for traditional didactic teaching in a medical school. Good quality CAL, however, requires substantial resources and high calibre staff to develop and maintain it. PMID- 8208154 TI - Introducing medical students to medical informatics. AB - Medical informatics (MI) has been introduced to medical students in several countries. Before outlining a course plan it was necessary to conduct a survey on students' computer literacy. A questionnaire was designed for students, focusing on knowledge and previous computer experience. The questions reproduced a similar questionnaire submitted to medical students from North Carolina University in Chapel Hill (NCU). From the results it is clear that although almost 80% of students used computers, less than 30% used general purpose applications, and utilization of computer-aided search of databases or use in the laboratory was exceptional. Men reported more computer experience than women in each area investigated by our questionnaire but this did not appear to be related to academic performance, age or course. Our main objectives when planning an MI course were to give students a general overview of the medical applications of computers and instruct them in the use of computers in future medical practice. As our medical school uses both Apple Macintosh and IBM compatibles, we decided to provide students with basic knowledge of both. The programme was structured with a mix of theoretico-practical lectures and personalized practical sessions in the computer laboratory. As well as providing a basic overview of medical informatics, the course and computer laboratory were intended to encourage other areas of medicine to incorporate the computer into their teaching programmes. PMID- 8208155 TI - Advanced training in biomedical ethics: a curriculum in clinical specialty programmes. AB - Medical ethics play an essential role in the practice of medicine, in the care of individual patients, in the allocation of health care resources, and in the formulation of health care policy. A specific body of knowledge, 'biomedical ethics', has developed which applies ethical theory to biomedical practice. This has provided doctors with tools systematically to integrate rational ethical analysis into clinical decision-making. Training in the discipline of biomedical ethics is now required for all doctors in Canada. The goals, content areas, learning objectives, and learning methods considered appropriate for advanced training in this field for medical specialists are provided in this paper. Six topic areas are discussed: introduction to ethical theory, clinical ethics, professional ethics, ethics of human experimentation, ethics of health policy, and independent study. Ways this curriculum could be organized and evaluated are also offered. PMID- 8208156 TI - Integration of the surgical specialties into an innovative undergraduate curriculum. AB - A dilemma exists concerning the most effective way to incorporate surgical specialty teaching into an innovative undergraduate curriculum. Should the specialties form part of the core curriculum or should they be available as electives? The aim of this study is to describe an educationally sound and time effective way to give all students an exposure to the surgical specialties while maintaining the philosophy of an innovative curriculum. The SCORPIO method was used, on a trial basis, in 1992 to teach cardiothoracic surgery, neurosurgery, plastic surgery and urology to fourth-year medical students at a university teaching hospital. The teaching was evaluated by comparing group pretest performance with a posttest assessment given one month after each of the teaching sessions. Student perceptions were assessed by a questionnaire and a time analysis was carried out comparing SCORPIO with the traditional ward tutorial system. Students completed the sequence pretest, teaching and posttest on 169 occasions. Group performance increased from a pretest mean 28% (SD16) to a posttest mean 44% (SD13) P < 0.0001. Student acceptance was favourable, with high ratings given to the structured, problem-based style of teaching. The time to run the programme was one-eight that to teach by the ward tutorial system. This teaching model is a practical way to incorporate the surgical specialties into the core curriculum of a school moving towards a student centred, problem-based, integrated curriculum. PMID- 8208157 TI - Audit: teaching medical students in general practice. AB - Audit is being seen as an increasingly important topic for medical students. Many departments of general practice in the UK now incorporate audit as part of their course work. It remains controversial as to whether this is perceived to be worthwhile by the students. Following an introductory seminar final-year medical students at the University of Glasgow were asked to perform a case-note review of 10 randomly chosen diabetic patients for a number of process and outcome measures during their practice attachments. Feedback was given in their final teaching session. 128/153 (84%) students completed an evaluation of the course on their knowledge and attitudes to audit. Unsurprisingly, 39% found the data collection boring or very boring; however, 60% found the feedback session very interesting or interesting. Both the data collection and the feedback were considered relevant by the majority of students (57% and 70% respectively). Students' self reported knowledge also dramatically increased (P < 0.0001). PMID- 8208159 TI - Using tracers to link health services to training through evaluation. AB - The tracer concept was applied to evaluate the delivery of family health care and the training of family health workers. A retrospective evaluation permitted linking the products of care to process, input and context, by isolating and analysing potential factors contributing to a limited number of representative concerns. Contributory learning deficiencies identified in health workers, one input to health care as well as a product of training, enabled the evaluation of training programmes to be focused on related segments of the courses. The latter were evaluated through a pathway analysis which followed the same deficiency model as the evaluation of health care. Links were thus established between the traditionally compartmentalized training and service sectors in health. PMID- 8208158 TI - Attending rounds on in-patient units: differences between medical and non-medical services. AB - The objective of this cross-sectional observational study was to quantify communication patterns between teachers and trainees on in-patient attending ward rounds and assess trainees' perceptions of the effectiveness of teaching interactions. Sixty-nine in-patient ward rounds on medical and non-medical teaching services at a university hospital and its affiliated VA Medical Center were studied. Teaching rounds were observed and audiotaped, and trained raters coded verbal interchange for its location, speaker identity and topic of the exchange. One to three days following the teaching rounds, residents and students were interviewed and completed a questionnaire concerning recollections of the content of the session. Medical rounds lasted a mean of 90 minutes, while non medical rounds averaged 38 minutes. Medical teams spent more time than non medical teams on case presentations and discussions of diseases not directly related to patient care. Both groups averaged approximately 10 minutes directly interacting with patients, and equal times were spent speaking by the teacher and trainees. The role of postgraduate year 1 residents and medical students primarily was to recite details of patients' clinical condition. Twenty-nine per cent of trainees were unable to recall a specific teaching point from rounds when interviewed 1-3 days later. Duration and content of in-patient rounds differed on medical and non-medical services. For both, discourse tended to be hierarchical, with those at different training levels adhering to specific roles. Bedside patient interactions were limited. The content recalled by students and house staff suggests that new, more effective educational paradigms are needed. PMID- 8208160 TI - Inadequate recording of alcohol-drinking, tobacco-smoking and discharge diagnosis in medical in-patients: failure to recognize risks including drug interactions. AB - The records of 62 men and 43 women, 14-88 years old, admitted to general medical wards in a public teaching hospital during 1991 were examined for discharge medications and for the recording of alcohol-drinking, tobacco-smoking and discharge diagnosis. Drinking and smoking status was unrecorded in 22.9% and 21.9% of patients respectively. Twenty-four patients had 31 potential drug interactions which were related to the number of drugs prescribed and to drinking alcohol; 10.5% of the patients had interactions involving alcohol and 2.9% tobacco. Six patients received relatively or absolutely contraindicated drugs, including one asthmatic given two beta-blockers. The drugs prescribed indicated that some patients had conditions such as gastro-oesophageal disorders, diabetes and obstructive airways disease which had not been recorded. Inadequate recording of diagnoses, alcohol and smoking status creates risks to patients and may cause opportunities for preventive care to be missed. This study provides the basis for the development of undergraduate and postgraduate education programmes to address these issues and so decrease risks to patients which arise from inadequate recording practices. Incomplete diagnoses also adversely affect hospital funding where this depends on case-mix diagnostic groups. Quality assurance programmes and other strategies are being implemented to improve medical recording and prescribing habits. PMID- 8208161 TI - The changing medical profession: implications for medical education. World Summit on Medical Education, Edinburgh, 8-12 August 1993. PMID- 8208162 TI - Medical students' well-being. PMID- 8208163 TI - Learning to cope: stress and medical career development in the United Kingdom. AB - This review addresses medical career development in the United Kingdom. This differs from other countries, and the structure of both undergraduate and postgraduate medical education is described in some detail. Problems identified from research surveys are given, and some of the proposals made to solve them are discussed. It is concluded that three main issues need to be addressed: greater attention needs to be paid to educational processes; teachers and their teaching must be valued; and appropriate support systems should be provided for medical students and trainees. PMID- 8208165 TI - Medicine and stress. PMID- 8208164 TI - Health policies and procedures for medical students at US medical schools: a progress report. AB - This paper presents the current status of school health policy at US medical schools and discusses implications for medical students with respect to physical health and occupational risks. The authors discuss the responsibility of schools to ensure that students are healthy and fit, both for their own benefit and to provide models of good health maintenance for their future patients. Schools have an obligation to monitor public safety issues, particularly in cases of chemical impairment, student mistreatment and infection control procedures. PMID- 8208166 TI - Mental health service for medical students. AB - The authors describe the problem of impairment of medical students from the point of view of mental health professionals who have directed a large and successful evaluation and referral service for students suffering from a wide array of stress-related and mental disorders. They outline the nature of the impairment problems, the history of the efforts at their medical school to address these problems, and their recent experience in providing mental health services to students who are referred for evaluation and treatment. Diagnostic data, referral and the implications of mental disorders for medical students are discussed. The authors offer some suggestions for the formation of student well-being committees prior to the implementation of student assistance programmes to address the problems of substance abuse. PMID- 8208167 TI - A programme for treating chemically dependent medical students. AB - The first American programme for chemically dependent medical students at the University of Tennessee, Memphis is described. The goals of the Aid for the Impaired Medical Student (AIMS) Program are to provide confidential treatment for chemically dependent medical students, to assure that recovering students are able to resume their education, and to protect patients and others from the harm that may be caused by impaired students. The Program is administered by the AIMS Council, consisting of medical professionals and elected student representatives. The Council oversees the management of cases, including investigation of students who may be impaired, intervention when chemical dependency is suspected, diagnostic evaluation, treatment and aftercare, and post-recovery advocacy for students. The Program's experience includes 18 cases of suspected chemical dependency, with four self-referrals and 14 students referred by third parties. Eleven students have been diagnosed as chemically dependent and have completed treatment programmes. Nine have maintained recovery and eight have graduated. One student subsequently relapsed and committed suicide. Obstacles in programme implementation have involved absence of perceived need, the view that chemically dependent students should be dismissed from school, and reluctance of students to report classmates. Resources have included highly respected student representatives, a supportive administration, assistance of the impaired physicians programme, and medical insurance and professional courtesy to defray costs. Although the number treated has been modest, the AIMS Program is an important vehicle for training students regarding chemical dependency and their professional obligations toward impaired colleagues. PMID- 8208169 TI - The first year at medical school: some findings and student perceptions. AB - This paper will first summarize briefly some results from parallel studies of first-year medical students at the University of Edinburgh, Scotland and University of Houston, Texas, USA. These findings have been presented more fully elsewhere (Surtees & Miller 1990; Miller & Surtees 1991; Miller & Lloyd 1991; Miller 1994) and here the emphasis will be on the Edinburgh results. Following this, some new material will be set down, reflecting the Edinburgh students' comments to the interviewers about their courses. PMID- 8208168 TI - Enhancing the psychological health of medical students: the student well-being committee. AB - Medical schools' emphasis on technical excellence is sometimes at the expense of social and emotional development. This paper describes a programme, orchestrated by a vital Well-Being Committee, that involves students in a wide range of activities to enhance social and emotional well-being. The primary prevention of emotional impairment is the goal. PMID- 8208170 TI - Medical statistics: content and objectives of a core course for medical students. AB - British medical school teachers of medical statistics aspire to teach statistical concepts without requiring medical students to undertake every statistical technique in the book. In the typical course of 20 to 30 hours, about 50 topics are taught, usually requiring the student to perform a technique. In a survey of current practice in 20 courses it is shown that a core syllabus of 36 topics, including 14 techniques to be performed, is feasible for almost all existing courses. Clear student learning objectives now need to be agreed to encapsulate this syllabus. PMID- 8208171 TI - A case-based anatomy course. AB - A course is described in which the students give consideration to clinical cases as they review their current knowledge, and follow a set protocol which guided them in preparing their learning. The students are required to examine a case history, put down as key words either their first answer or the knowledge they consider they would need to answer specific questions. They then select stations at which additional information, wet specimens, models and radiological images assist them in upgrading their knowledge. They complete the exercise by writing a final answer to the questions on the case. The tutor is able through examination of the key words to determine the knowledge of the students as they enter, and confirm appropriate learning by inspection of the final answer. The students are able to identify their own deficiencies, develop strategies for thinking and learning, resulting in the acquisition of expertise in problem solving, and extend their communication skills by working with colleagues. While the course was designed for second-year anatomy teaching it could be applied to other disciplines. PMID- 8208172 TI - Simple surgical audit: an aid to undergraduate curriculum development. AB - This study investigates the usefulness of a simple surgical audit in designing the undergraduate surgical curriculum in the newly established medical school of the United Arab Emirates. The audit system was designed for use by people previously unaccustomed to this activity. The pattern of disease is found to be biased towards a young male expatriate population. It has been possible to predict the likelihood of a particular disease being available for teaching purposes and has drawn attention to the relative absence of some conditions which are commonly found elsewhere. Allowances need to be made for this and teaching strategies other than those which require direct patient contact should be considered. This method of curriculum design may find use in other places where health care patterns are changing. PMID- 8208173 TI - Portfolio learning: a proposal for undergraduate cancer teaching. AB - This paper describes a randomized study to evaluate a longitudinal approach to undergraduate education using cancer patients and cancer medicine as a model. Medical students were randomized to the study or control group. Those in the study were allocated to tutors (general practitioners or consultants) in groups of three. Each student was allocated three consenting patients with cancer to follow longitudinally. They compiled a portfolio to record events, interactions, relevant articles, etc. based around the patients' case histories. The students received tutorials to provide direction, discussion and support bimonthly during the course. Evaluation was by central review of the portfolios, appraisal in the clinical competence examination and hidden questions in the standard MCQ examinations. The aim was to provide the learner with a personal experience of cancer patients at all stages of the disease, an understanding of the natural history of cancer and an insight into the impact of the disease and its treatment on the patient and family. The study evaluates whether these aims were achieved to a greater extent in those students receiving the portfolio teaching compared with a control group receiving the standard curriculum teaching only. PMID- 8208174 TI - Stress, coping and health: enhancing well-being during medical school. AB - Medical education can be a health hazard for many students, and far-reaching reforms are needed to improve it. This article reviews the literature on stress, coping and health during undergraduate medical education. The conclusions drawn from this review are used as a basis for advancing recommendations to improve medical education. It is essential to incorporate the principles of health promotion and disease prevention throughout medical education in order to minimize and prevent later burn-out and impairment. Healthy medical students are likely to become healthy doctors who can then model and promote healthy lifestyles with their patients. This preventive approach to health care can lead to an improvement in our health care delivery system. PMID- 8208175 TI - Influence of motivational and demographic factors on performance in the medical course: a prospective study. AB - A questionnaire was completed by students entering the University of Queensland (Australia) MB BS course in 1983 and 1984 (n = 399). It contained wide-ranging questions regarding the decision to enter medicine, including how, why and when the decision was reached. Demographic data were also collected. All but two students have now completed their involvement with the course. The most important determinant of qualifying MB BS was geographical, metropolitan students doing so in greatest proportion. High levels of course performance were predicted by father's occupation, and being aware of a widely held attitude, namely that it would be a pity not to enter medicine if able to do so. Several gender differences are noted. Finally, it was noteworthy that the predictive aspects of questionnaire responses did not lessen as students progressed through the course. PMID- 8208176 TI - Community-based learning in obstetrics for undergraduate medical students. AB - Medical students on their obstetrics and gynaecology attachment were randomly assigned to attend hospital (n = 24) or general practice (n = 18) obstetric clinics once weekly for 4 weeks. The students completed self-assessment questionnaires at the beginning and end of the attachment. There was a significant improvement in the level of knowledge and skills required for antenatal care, care in labour and postnatal care by the end of the attachment, with no difference between hospital or general practice groups. There was a significant increase in the level of interest in the future practice of obstetrics only in the general practice group. However, this difference could be explained by the greater number of students in the general practice group who were by chance in the 'no or don't know' category at the start of their attachment. We conclude that general practice based clinical teaching of obstetrics can be a suitable alternative to hospital-based clinical teaching for undergraduate medical students. PMID- 8208177 TI - The direct clinical examination: an alternative method for the assessment of clinical psychiatry skills in undergraduate medical students. AB - Because of dissatisfaction with the traditional long case procedure as a method of examining the clinical competence of medical students undertaking a psychiatry term, an alternative 'direct' method whereby two examiners observe the interaction between student and patient has been developed and is described. This method of examining allows the examiners to set and evaluate case-specific tasks. It is demonstrated that the two examiners achieve satisfactory interrater reliability both with respect to the mark awarded and the difficulty the patient presents and that, as one would wish, these two measures do not correlate. Students' opinions regarding the examination were assessed pre- and post examination using visual analogue scales. The students found the examination stressful but rated the method as an appropriate form of clinical assessment both before and after their examination. The method is seen as having several advantages which must be set against the disadvantage of its being relatively expensive of examiners' time. PMID- 8208178 TI - The role of psychology in the teaching of medical ethics: the example of informed consent. AB - Over the past two decades, psychology has become well established in the medical curriculum. This paper argues that it has much to say about ethical issues, particularly informed consent. Because psychology addresses such areas as providing information, ensuring understanding of this information, identifying situations in which coercion occurs and assessing competence, its inclusion in the curriculum is justified on ethical as well as scientific grounds. This has several implications, including the allocation of resources, collaboration with health and clinical psychologists and the timing of the teaching. PMID- 8208179 TI - Student-initiated revision in child health. AB - Most teaching of child health in Cardiff takes place in block attachments of 8 weeks. There is an introductory seminar of 2 days followed by a 6-week clinical attachment in a district general hospital in Wales, and then a revision period of one week designed to help students formalize and structure their basic knowledge and to clarify aspects of child health which they may have had difficulty in understanding. The revision programme has to take into account: the short time available, the small number of teaching staff, the most relevant basic knowledge and active participation by the student. This paper describes how this week has been improved through the use of student-initiated revision (SIR). The students' appraisal of this revision and in particular SIR is presented. PMID- 8208180 TI - Dealing with death and dying. AB - We instituted two thanatology seminars for medical students and residents which emphasized feelings more than objective data. The seminars began with students filling out a death certificate on themselves. Eighty-four per cent predicted that their own probable cause of death would be from an acute illness. Discussion and reflection on this experience helped them realize how difficult it would be to deal with a chronic illness. By answering a question about what they were most grateful for, they became aware that they valued family and friends most highly. We believe that this experience legitimized feelings which form the basis of empathy. PMID- 8208181 TI - An experiment in problem-based learning. AB - Problem-solving skills are important for medical students and problem-based learning (PBL) is especially suited to general practice. Therefore an experiment using a form of PBL was introduced into a new 4-week course in general practice for final rotation students at the University of Glasgow in the session 1992-93. The experiment aimed to introduce students to an alternative method of learning to the traditional one previously used by them in their course, to encourage teamwork and to encourage the use of alternative methods of obtaining information. The method, centred around allowing the students to investigate problems they choose themselves, is described. The evaluation of the course by written standard form, free written comments and audiotape recorded interviews with a one in four sample of the class is presented. The students selected many interesting problems and used many different and unusual sources of information in researching them. This method of learning was compared with the parallel lecture course and was thought by the students to be more interesting but less relevant than the lecture course. The experiment showed that it is possible to introduce a problem-based form of learning into a new course in parallel with more traditional methods of teaching and for it to be at least partially successful for students much more used to a traditional didactic curriculum. Ways of improving the course in the future to make it more sensitive to the students' learning needs are discussed. PMID- 8208182 TI - Reliability of consumer assessment of communication skills in a postgraduate family practice examination. AB - Examinations of competence which may affect career prospects require measures which are of high reliability, and which can be demonstrated to be valid. In a New Zealand summative postgraduate examination of competence in family practice the doctor-patient communication skills of candidates were assessed by nonmedically trained nominees of community organizations. The assessments were based on direct observation of the candidates' encounters with simulated patients. To estimate the reliability of the consumer examiner, after the examination the examiners re-scored a random selection of video-taped candidate encounters. The test-retest correlations of consumer scoring were demonstrated to be at a level consistent with adequate examination reliability (confidence interval 0.59-0.98). Consumers may be valuable as a resource for the training and assessment of the communication skills of medical practitioners. PMID- 8208183 TI - Smoking among health professionals. AB - A cross-sectional prospective study was conducted between the period December 1991 and November 1992, to identify the extent of smoking among practising doctors and other health professionals in general hospitals and health clinics in Al-Ain, United Arab Emirates. The study population consisted of 300 health professionals (doctors, specialists both clinical and non-clinical, pharmacists and dentists). They were handed self-administered questionnaires adapted from the World Health Organization standard questionnaire on smoking among health professionals. Among the responding 268 (89%) health professionals 197 (73.5%) were men, and 71 (26.5%) women. Among the men health professionals 86 (43.7%) were current smokers, 24 (12.2%) were ex-smokers and 87 (44.2%) were non-smokers, while among the women health professionals 4 (5.6%) were smokers, 1 (1.4%) was an ex-smoker and 66 (93%) were non-smokers. Doctors were uniformly aware of the detrimental effects of smoking, particularly its association with lung cancer, coronary artery disease, chronic bronchitis, and laryngeal cancer, and this was the major reason for their abstaining or wanting to quit the habit. The relationship of smoking with bladder cancer, soft tissue lesion (mouth and lip) and neonatal death was not well appreciated. Counselling patients about the hazards of smoking was practised significantly less often by doctors who smoked. The majority (83.6%) expressed the need for specific training for counselling patients to stop smoking. The options favoured by the health professionals for preventing smoking included a ban on tobacco advertising, specific health warnings on cigarette packets and restriction on smoking in public places, particularly in hospitals and clinics. PMID- 8208184 TI - An innovative course: 'vers l'Europe 1992'. AB - A course in using French in the consultation is described. This proved a popular exercise with many general practitioners wishing to attend. A previous knowledge of French was essential for acceptance. The course consisted of 10 meetings with homework. Both formal and informal assessment of the course showed the success both from a group and an individual point of view. PMID- 8208185 TI - Edinburgh '93. PMID- 8208186 TI - Training for medical teachers: a UK survey, 1993. AB - Opportunities and resources for training of medical teachers have been criticized in recent UK reports. A survey of undergraduate and postgraduate medical deans showed that training courses were available at most institutions, though only a few were specifically designed for medical teachers. Many new and specific courses are being planned and many new appointments are being made in medical education at both medical school and postgraduate levels. While the outcome of greater resources for training of medical education cannot yet be determined, we conclude that criticisms are being speedily addressed. PMID- 8208187 TI - Asia-Oceania and the global epidemic of diabetes. PMID- 8208188 TI - The surgical treatment of morbid obesity: current status and prospects. PMID- 8208189 TI - Sports-related eye injuries. AB - OBJECTIVE: To: (i) determine the magnitude and describe the spectrum of sports related eye injuries; (ii) compare the sporting profile variations within Australia and overseas; and (iii) provide recommendations to help decrease the frequency and severity of eye injuries in sports. DESIGN AND SETTING: Descriptive study of sports-related eye injuries identified from a cross-sectional survey of ocular trauma treated in an eye hospital during a two-year period from November 1989 to October 1991. RESULTS: Although sports injuries comprised only 5% of all eye trauma, they accounted for a disproportionately high ocular morbidity, representing 22% of hospital admissions. Most patients were admitted for hyphaema (81%), but there were eight ruptured globes and 20 other cases required surgical repair. For those hospitalised for serious injuries, 19% were legally blind (visual acuity < or = 6/60) and 10% had visual acuity between 6/18 and 6/36 initially, with 29% of patients recording a visual loss in excess of 50% incapacity (< or = 6/18) at three months after injury. CONCLUSION: Eye injuries were most frequently caused by squash, badminton, Australian Rules football and cricket, a sports profile distinctly different from those of the United States and United Kingdom. That none of the players in may study had worn correct eye protection offers a wide scope for preventing injuries in what should be safe recreational pastimes. PMID- 8208190 TI - The epidemiology of blindness and trachoma in the Anangu Pitjantjatjara of South Australia. AB - OBJECTIVE: To determine the prevalence of trachoma and blindness in the Aboriginal population in the Anangu Pitjantjatjara and Yalata lands of South Australia. DESIGN AND SETTING: A population-based prevalence survey undertaken in conjunction with routine South Australian Aboriginal Trachoma and Eye Health Program trips during 1989 and 1990. RESULTS: A group of 1514 individuals aged 0 90 years, or approximately 58% of the estimated Aboriginal population in the Anangu Pitjantjatjara and Yalata lands, was examined. Active inflammatory trachoma was found in 17.6% of the group (266 individuals), cicatricial trachoma in 25.2% (382) and binocular blindness (Australian definition) in 1.5% (22). The major causes of monocular and binocular blindness were trachoma, cataracts and trauma. Two per cent of women (17 of 849) were blind, compared with 0.8% (5 of 665) of men (odds ratio, 3.22; 95% confidence interval, 1.03-10.43). CONCLUSIONS: Although trachoma is still endemic in the "traditional" Aboriginal population of SA, its prevalence and severity appear to be less than previously recorded. However, the prevalence of blindness is comparable with that found in developing countries and the causes are still largely preventable. Further effort is required to reduce trachoma and preventable or treatable blindness in these communities. PMID- 8208192 TI - Misconceptions about Leber hereditary optic neuropathy. PMID- 8208191 TI - Prevalence and risk factors for retinopathy in adolescents with type 1 diabetes. AB - OBJECTIVES: To establish the prevalence of, and risk factors associated with, diabetic retinopathy in an Australian adolescent diabetes clinic population. DESIGN: A prospective longitudinal study; baseline findings. PATIENTS: Two hundred and fifty-five patients with Type 1 (insulin-dependent) diabetes mellitus assessed by our service were studied. Entry criteria were: age 11.0-19.9 years; diabetes duration of at least two years; and gradable fundus photographs of at least one eye. MAIN OUTCOME MEASURES: The presence and severity of retinopathy, as assessed by the grading of stereoscopic fundus photographs. Possible risk factors assessed were age, sex, diabetes duration, pubertal stage, blood pressure, glycaemic control and total cholesterol level. RESULTS: The prevalence of retinopathy was 42%; all of those affected had mild background retinopathy. Highly significant associations were found with glycaemic control and both total and prepubertal duration of diabetes. No associations were found with age, sex, pubertal stage, blood pressure or total cholesterol level. CONCLUSIONS: The high prevalence of early diabetic retinopathy in this group of Australian adolescents is comparable to recent reports from other centres. The significant associations with glycaemic control and duration of diabetes provide further strong evidence for the benefit of optimal glycaemic control during adolescence. Our finding that the prepubertal years of diabetes contribute to the development of retinopathy suggests that glycaemic control before puberty should also be optimised. The planned follow-up of this cohort will establish the risk of progression to vision threatening retinopathy and allow risk factors to be further evaluated. PMID- 8208193 TI - Extraordinary prevalence of non-insulin-dependent diabetes mellitus and bimodal plasma glucose distribution in the Wanigela people of Papua New Guinea. AB - OBJECTIVE: To determine the current prevalence of impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) in Melanesians of three coastal Papua New Guinean communities, to relate this to previous studies, and to investigate plasma glucose distributions in these populations. DESIGN: Cross sectional survey, using 75 g oral glucose tolerance tests and World Health Organization criteria. SETTING: Rural Papuan villages of Wanigela and Kalo, and Wanigela people of the urban squatter settlement of Koki, Port Moresby. SUBJECTS: All adults aged 25 years or more living in the three communities were eligible, with response rates of 77.2% (Koki), 88.1% (Wanigela) and 72.5% (Kalo). MAIN OUTCOME MEASURES: Prevalence of abnormal glucose tolerance, risk factor levels, fasting and two-hour plasma glucose concentration. RESULTS: Age-standardised prevalence of NIDDM in Koki Wanigelas was 27.5% in men and 33.0% in women; an additional 20.5% of men and 22.0% of women had IGT. Even in the youngest age group (25-34 years), 36.5% of subjects had abnormal glucose tolerance. The overall prevalences of NIDDM and IGT in rural Wanigelas were 11.7% and 17.0% respectively. In Kalo both were uncommon. The prevalences of IGT and NIDDM in Koki had doubled over a 14-year period. The age-standardised prevalence of abnormal glucose tolerance in the Koki Wanigelas is the second highest in the world after the Arizona Pima Indians, and higher than in Micronesian Nauruans, even though the latter are more obese. Both fasting and two-hour glucose concentrations in all age groups in Koki were clearly bimodal, a mixture of two log-normal distributions. CONCLUSIONS: The Wanigela people of Papua New Guinea have an extra-ordinary susceptibility to glucose intolerance which is exposed after adoption of modern lifestyle habits. A "founder effect" may explain the high frequency of a diabetogenic genotype in this population. PMID- 8208194 TI - Suicide and self-harm in Tasmanian children and adolescents. AB - OBJECTIVES: To examine rates of suicide by Tasmanians less than 20 years of age, to compare them with rates for Australia as a whole, and to report a clinical study of child and adolescent self-harm in Tasmania. DESIGN: Australian Bureau of Statistics data on suicides by 0-19-year-olds in Tasmania and Australia and population estimates were used to calculate and compare suicide rates for the period 1965-1991. The self-harm study involved 36 females and 16 males presenting to the accident and emergency department of a general hospital. They were studied by means of structured interview and scales of personal/family functioning and beliefs. Controls were individually matched with patients with no psychiatric condition. RESULTS: During 1965-1991, the suicide rate in Tasmanian males aged 15 19 years was higher than that of mainland Australian males and had increased during the last 10 years of this period. Suicide rates for males, both in Tasmania and mainland Australia, were higher than the corresponding rates for females. Among females aged 10-14 years or 15-19 years, the rates for Tasmania were not different from those of the mainland counterparts. The rate for 15-19 year-old Tasmanian females was higher during the last decade of the study period than in earlier years. Common motivations for self-harm were to die or to escape an impossible situation, rather than to attract the attention of others. Most adolescents had serious personal and interpersonal problems, usually involving family dysfunction, including parental separation, physical abuse and lack of a family confidant, when compared with controls. Ingestion of medication (most frequently paracetamol) was the most common method of self-harm. CONCLUSIONS: The suicide rate in 15-19-year-old Tasmanian males is higher than the mainland rate and rising. Self-harm in adolescence is associated with serious personal and interpersonal problems which must be identified before effective counselling can begin. The formation of multidisciplinary teams for the immediate assessment and support of self-harming adolescents and their parents is recommended. PMID- 8208195 TI - Non-accidental head injury in children. AB - AIMS: To analyse the clinical features, social circumstances, investigations and outcome of 49 children with significant non-accidental head injury admitted to The Prince of Wales Children's Hospital between 1979 and 1993. CLINICAL FEATURES: Age ranged from one month to eight years, with 30 children less than one year old. There were 28 boys and 21 girls. Thirty-three were in the care of a parent. Eleven of these were known to the Department of Community Services and 22 were from families with stressed socioeconomic circumstances characterised by deprivation. In 44 cases the history was incompatible with the clinical findings. On admission, 21 had marked depression of awareness, with a Glasgow Coma Scale score (GCS) of 9 or less. Eleven of this group were fitting. Seizures were present in a further 13 children who were semi-purposeful (GCS > 9). Twenty-eight had retinal haemorrhages and 35 had soft tissue scalp contusions, 23 in association with skull fracture. Twenty-six had associated injuries. Seven children died. Of the 42 survivors at the time of discharge, 19 had severe motor disability associated with other deficits. Twenty-four were returned to the care of their families. CONCLUSIONS: Retinal haemorrhage and unconsciousness on admission (GCS < or = 9) were positively associated with a poor outcome (P < 0.001 and 0.002, respectively). Cerebral oedema found on computerised tomography was positively associated with severe motor disability on discharge (P < 0.001). Lowest socioeconomic circumstances appeared to be a risk factor for occurrence of injury: 22 of 49 children came from circumstances of deprivation. PMID- 8208196 TI - Non-fatal injuries to young Victorians, 1986-1991. AB - OBJECTIVES: To describe the epidemiology of non-fatal injuries sustained by young Victorians requiring hospitalisation, and to provide baseline data to establish and evaluate injury prevention programs. DATA SOURCE: The Victorian Inpatient Minimum Database, as modified for use by Monash University Accident Research Centre. DESIGN: A five-year (July 1986 to June 1991) retrospective epidemiological study of 56,209 15-24-year-olds admitted to Victorian public hospitals because of injury. RESULTS: The annual Victorian hospital admission rate of 15-24-year-olds with injuries was 1609 per 100,000. The major causes of admission were, in order of frequency, transport injuries, falls (excluding falls in sport), sports injuries, assault, and self-inflicted injuries. The cost to the Victorian community in hospital expenditure is at least $31.5M per year. Of these injuries, 73.9% were unintentional; however, intentional self-inflicted and assault injury rates were higher for both adolescents (15-19 years) and young adults (20-24 years) compared with other age groups. CONCLUSION: High rates of injury for young people have been found, imposing a considerable burden on the community. As many injuries are preventable, the risk factors warrant further investigation. In particular, control measures could help reduce sports, transport-related and intentionally inflicted injuries. PMID- 8208197 TI - Japanese B encephalitis vaccine. Time for a reappraisal? PMID- 8208198 TI - The use of poorly validated and expensive technology. PMID- 8208199 TI - Petrol sniffer's encephalopathy. PMID- 8208200 TI - Youth suicide in Victoria: a retrospective study. PMID- 8208201 TI - The pros and cons of transdermal nicotine therapy. PMID- 8208202 TI - Organic nitrate therapy for angina pectoris. PMID- 8208203 TI - Trends in antenatal folate supplementation in the Tasmanian cohort study. PMID- 8208204 TI - Epilepsy in pregnancy--neural tube defects and folate. PMID- 8208205 TI - National health intelligence. PMID- 8208206 TI - Permethrin: a Top End viewpoint and experience. PMID- 8208207 TI - Gynaecomastia and amlodipine. PMID- 8208208 TI - HIV western blot test. PMID- 8208209 TI - A generalized pencil beam algorithm for optimization of radiation therapy. AB - An iterative pencil beam algorithm for optimization of multidimensional radiation therapy dose plans has been developed. The algorithm allows the use of both physical and radiobiological treatment objective functions and allows arbitrary sampling such as straight Cartesian grids with linear or nonlinear sampling functions or random sampling. The algorithm can account for and optimally combine almost all the degrees of freedom at an advanced radiotherapy clinic, such as different beam modalities and spectra, beam directions, beam fluence distributions, and time-dose fractionations. The algorithm allows for external charged and neutral beams as well as intracavitary and interstitial sources to be optimally combined. A quantity termed the generalized fluence vector is introduced, combining fluences and energy fluences from external beams as well as the radiation source densities of intracavitary and interstitial sources or external source distributions. The positivity constraint on the generalized fluence can therefore be applied directly during the optimization procedure. The convergence properties and the required iteration time of the algorithm are discussed. Several examples with combinations of photon and electron beams of different energies and directions of incidence are presented. The optimization has been made with the treatment objective to maximize the probability of achieving tumor control without causing severe complications in healthy normal tissues. PMID- 8208210 TI - Implementation of a three-dimensional compensation system based on computed tomography generated surface contours and tissue inhomogeneities. AB - A computed tomography (CT) based system that compensates for patient surface contour and internal tissue inhomogeneity was implemented in our clinic. The compensators are fabricated with a mixture of tin granules and bee's wax. The tin/wax mixture was optimized for tin granule size and tin granule to wax ratio. The narrow beam attenuation coefficients were measured for 4-, 6-, 10-, and 24-MV photon beams. The compensator design and fabrication methodology were verified by measuring the dose distribution for a known surface contour irradiated with a compensated beam and for a known inhomogeneity that was submerged in a water phantom and irradiated with a compensated beam. For the surface contour, the uncompensated isodose levels varied by as much as 10% in the compensation plane and the compensator restored the isodose level to a variation of less than 1.3%. Measured and calculated doses for this surface contour were found to differ by less than 3.4%. For the inhomogeneity, the uncompensated isodose levels varied by 27% in the compensation plane and the compensator restored the isodose level to a variation of less than 1.5%. Measured and calculated doses for the known inhomogeneity were found to differ by less than 2%. Measurements of depth-dose curves indicate that the presence of the compensator in the beam does not significantly increase the surface dose. Twenty-six compensators have now been fabricated for clinical cases. In these patients, dose variations as great as 19% occurred in the plane of compensation prior to placing the compensator in the beam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208211 TI - A method for the calculation of electron energy-straggling spectra. AB - To calculate electron beam dose distributions accurately, numerical methods of electron transport calculations must account for the statistical variation (or "straggling") in electron energy loss. This paper shows that the various energy straggling theories that are applicable to short path lengths all derive from a single statistical model, known as the compound Poisson process. This model in turn relies on three assumptions: (1) the number of energy-loss events in a given path length is Poisson distributed; (2) events are mutually independent; and (3) each event has the same probability distribution for energy loss (i.e., the same energy-loss cross section). Applying the principles of the compound Poisson process and using fast Fourier transforms, a new method for calculating energy loss spectra is developed. The spectra calculated using this method for 10, 20, and 30 MeV electrons incident on graphite and aluminum absorbers agreed with Monte Carlo simulations (EGS4) within 1% in the spectral peak. Also, stopping powers derived from the calculated spectra agreed within 1.2%, with stopping powers tabulated by the International Commission on Radiation Units and Measurements. Several numerical transport methods "propagate" the electron distribution (in position, direction, and energy) over small discrete increments of path length. Thus the propagation of our calculated spectra over multiple path length increments is investigated. For a low atomic number absorber (graphite in this case), calculated spectra agreed with EGS4 Monte Carlo simulations over the full electron range, provided the path length increments were sufficiently small (less than 0.5 g/cm2). It is concluded from these results that numerical methods of electron transport should restrict the size of path length increments to less than 0.5 g/cm2 if energy straggling is to be modeled accurately. PMID- 8208212 TI - The use of a radiochromic detector for the determination of stereotactic radiosurgery dose characteristics. AB - The measurement of absorbed dose as well as dose distributions (profiles and isodose curves) for small radiation fields (as encountered in stereotactic surgery) has been difficult due to the usual large detector size or densitometer aperture (> 1 mm) relative to the radiation field (as small as 4 mm). The radiochromic direct-imaging film, when read with a scanning laser microdensitometer (laser beam diameter 0.1 mm), overcomes this difficulty and has advantages over conventional film in providing improved precision, better tissue equivalence, greater dynamic range, higher spatial resolution, and room light handling. As a demonstration of suitability, the calibrated radiochromic film has been used to measure the dose characteristics for the 18-, 14-, 8-, and 4-mm fields from the gamma-ray stereotactic surgery units at Mayo Clinic and the University of Pittsburgh. Intercomparisons of radiochromic film with conventional methods of dosimetry and vendor-supplied computational dose planning system values indicate agreement to within +/- 2%. The dose, dose profiles, and isodose curves obtained with radiochromic film can provide high-spatial-resolution information of value for acceptance testing and quality control of dose measurement and/or calculation. PMID- 8208213 TI - The use of radiochromic film in treatment verification of dynamic stereotactic radiosurgery. AB - Standard silver-based films are usually too sensitive to be used as direct indicators of dose in dynamic radiosurgery because of optical saturation. This paper describes the use of a new radiochromic film to measure 6-MV radiosurgery doses and dose distributions in a head phantom. Dose calibration of the radiochromic film was performed in the range of 2.3-50.2 Gy using light of 632- and 530-nm wavelengths. Radiosurgery dose distributions were measured using the radiochromic film in a head phantom undergoing the same treatment as a patient, and were compared with the planned distributions. For an example case (nominal 2.0-cm-diam cone), film measurement verified the calculated dose distribution in one plane. The simple measurement technique described led to experimental uncertainties of +/- 0.1 cm for the 90% and 50% isodose lines, +/- 0.3 cm for the 20% line, and +/- 0.5 cm for the 10% line. Isocenter dose was measured with an uncertainty of +/- 3%. Refinements to the technique should allow more precise measurements. It is concluded that the radiochromic film, with some limitations, is a convenient and useful tool for dynamic radiosurgery quality assurance. PMID- 8208214 TI - Determination of beam orientation in radiotherapy planning. AB - A computer-assisted method for selecting beam orientation in a one-step procedure is presented. Inverse and adjoint techniques are developed to obtain the best beam directions. Both methods rely on determining the "path of least resistance" to radiation from the tumor location to the surface of the section. The effectiveness of beam directions is then determined by monitoring the dose distribution along the section boundary. The inverse and adjoint calculations are performed for three tumor cases using a two-dimensional discrete ordinates transport code. The proposed treatment plans from these calculations are verified against typical treatment plans. The new techniques improved the dose distribution in the treated section. The inverse calculations are useful in sections involving low-density tissues. The adjoint technique can effectively deal with multiple target volumes and/or sections with complex geometry. The proposed method is potentially useful in selecting beam orientations for three dimensional planning systems and in determining beam intensities in rotational and conformal therapy. PMID- 8208215 TI - Dose calculation in static or dynamic off-axis fields. AB - X-ray fields that are shifted away from the conventional central axis exhibit alterations in output, beam profile, and beam energy. An extension of a conventional dose calculation algorithm to correct for these perturbations is presented. This algorithm employs the product of three functions describing the dose at the center of the field at dmax, the relative off-center dose at dmax, and the relative dose at depth along a fanline passing through the point of interest. The nature of the problem is characterized, a basic data set necessary to support the algorithm is described and an abridged set of data that may assist in the development of an independent collimator dose calculation capability is presented. The appropriateness of this technique for both conventional and dynamically collimated fields is illustrated. PMID- 8208216 TI - Buildup region and depth of dose maximum of megavoltage x-ray beams. AB - The depth of dose maximum, dmax, of megavoltage x-ray beams was studied as a function of beam energy and field size for 6-, 10-, and 18-MV x-ray beams and field sizes ranging from 1 x 1 to 30 x 30 cm2. For a given beam energy, dmax increases rapidly with increasing field size at small fields, reaches a maximum around 5 x 5 cm2 and then gradually decreases with increasing field size for large fields. Monte Carlo simulations combined with measurements verified that the effect observed at small field sizes is caused by in-phantom scatter, while at large fields the effect is due to scatter contamination of the primary beam from the linac head. A comparison between the dmax behavior of flattened beams to that of unflattened beams indicates that the dmax decrease at large fields for flattened beams is caused mainly by contamination electrons which are produced in the flattening filter and further scattered by collimator jaws and air. PMID- 8208217 TI - A spatial-frequency dependent quantum accounting diagram and detective quantum efficiency model of signal and noise propagation in cascaded imaging systems. AB - The detective quantum efficiency (DQE) is a system parameter that can be used to accurately describe image noise transfer characteristics through many imaging systems. A simpler approach used by some investigators, particularly when evaluating new ideas and system designs, is to describe the system as a series of cascaded stages. Each stage may correspond to either an increase in the number of quanta (e.g., conversion from x-ray to optical quanta in a radiographic screen), or a loss (a detection or coupling probability). The number of secondary quanta at each stage per incident primary quantum is given by the product of all preceding gains, and can be displayed graphically for convenient interpretation. The stage with the fewest quanta is called the "quantum sink," limiting the pixel signal-to-noise ratio to less than the square root of the number of quanta per pixel. This conventional zero-spatial-frequency "quantum accounting diagram" (QAD), however, neglects the spatial spreading of secondary quanta and can seriously underestimate image noise. It is shown that this problem is avoided with the introduction of a spatial-frequency dependent QAD, expressed as the product of the gains and squared modulation-transfer functions (MTF) of each stage. A generalized expression is developed for the DQE of a cascaded imaging system that is dependent only on the gain, gain Poisson excess (related to the variance), and MTF, of each stage. A direct relationship is then shown to exist between the DQE and values in the QAD. The QAD of a hypothetical system consisting of a charge-coupled device camera and a scintillating screen is evaluated as an illustrative example. The conventional zero-frequency analysis suggests two quantum sinks occur with approximately equal importance: one in the number of x rays, and one in the number of optical quanta. The spatial-frequency dependent analysis, however, shows the optical quantum sink becomes severe and dominates at nonzero frequencies. The necessary increase in gain or optical numerical aperture required to prevent the optical quantum sink for spatial frequencies of interest is determined from the QAD analysis. The visual impact of this nonzero spatial-frequency quantum sink is shown in images generated using a Monte Carlo simulation of the cascading process. PMID- 8208218 TI - Longitudinal resolution in volumetric x-ray computerized tomography--analytical comparison between conventional and helical computerized tomography. AB - The primary advantage of helical computerized tomography (CT) is the capability of scanning a complete anatomical volume in a single breath hold. Due to the table motion and subsequent interpolation process, the slice sensitivity profile (SSP) in helical CT is worse than the response function of the detector array. In this paper, image longitudinal resolution in volumetric x-ray CT is analytically characterized, and a comparison made between conventional and helical CT. First, the SSPs are derived for both conventional and helical CT with the half-scan interpolation method under the condition that the table increment and detector collimation are the same. Then, the corresponding transfer functions are obtained for bandwidth determination, which directly describe the spatial resolution. Both one-tenth-cutoff and mean-square-root measures are used to quantify the bandwidth. Although it appears that broadening the SSP in helical CT could adversely affect longitudinal resolution, it is proved that for a given x-ray dose, helical CT allows substantially better longitudinal resolution than conventional CT due to its inherent retrospective reconstruction capability. To make full use of the potential of helical CT scan data, it is recommended that about five slices be reconstructed per table increment. Helical CT is superior in applications requiring a high longitudinal resolution. PMID- 8208219 TI - Scatter compensation in digital chest radiography using the posterior beam stop technique. AB - A new scatter compensation technique for computed radiography based on posterior beam stop (PBS) sampled scatter measurements and the bicubic spline interpolation technique was proposed. Using only a single exposure, both the clinical image and an array of scatter measurements, which were interpolated into a smooth scatter only image, were simultaneously acquired. The scatter was subtracted from the clinical image to generate the primary-only image. To gauge the accuracy of scatter estimation, both quantitative and interpolation errors were evaluated. The PBS measurements were compared against the standard beam stop method at 16 locations in an anatomical phantom, resulting in quantitative errors of 2.7% relative to the scatter or 6.8% relative to the primary. Also measured were the interpolation error over 64 interpolation sample locations and 64 midpoint sample locations in the anatomical phantom. The combined interpolation error was 1.9% relative to the scatter or 8.0% relative to the primary. At the interpolation sample locations, the errors were identical between the phantom radiograph and digital portable chest radiographs from five patients. By summing the quantitative and interpolation errors in quadrature, the overall error of the PBS SISTER (scatter interpolation-subtraction technique for radiography) method was 3.3% relative to the scatter or 10% relative to the primary, which was adequate for dual-energy imaging purposes (less than 10% error relative to the scatter or 20% relative to the primary). The change of image contrast, noise, and signal-to noise ratio (SNR) at six locations in the anatomical phantom were quantitatively analyzed. Contrast and noise were equally enhanced in all anatomical regions, resulting in approximately the same SNR before and after compensation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208220 TI - Computerized detection of masses in digital mammograms: automated alignment of breast images and its effect on bilateral-subtraction technique. AB - An automated technique for the alignment of right and left breast images has been developed for use in the computerized analysis of bilateral breast images. In this technique, the breast region is first identified in each digital mammogram by use of histogram analysis and morphological filtering operations. The anterior portions of the tracked breast border and computer-identified nipple positions are selected as landmarks for use in image registration. The paired right and left breast images, either from mediolateral oblique or craniocaudal views, are then registered relative to each other by use of a least-squares matching method. This automated alignment technique has been applied to our computerized detection scheme that employs a nonlinear bilateral-subtraction method for the initial identification of possible masses. The effectiveness of using bilateral subtraction in identifying asymmetries between corresponding right and left breast images is examined by comparing detection performances obtained with various computer-simulated misalignments of 40 pairs of clinical mammograms. Based on free-response receiver operating characteristic and regression analyses, the detection performance obtained with the automated alignment technique was found to be higher than that obtained with simulated misalignments. Detection performance decreased gradually as the amount of simulated misalignment increased. These results indicate that automatic alignment of breast images is possible and that mass-detection performance appears to improve with the inclusion of asymmetric anatomic information but is not sensitive to slight misalignment. PMID- 8208221 TI - Digital image subtraction of temporally sequential chest images for detection of interval change. AB - An automated digital image subtraction technique for temporally sequential chest images has been developed in order to aid radiologists in the detection of interval changes. A number of small regions of interest (ROIs) are selected automatically in the lung areas of two temporally sequential chest images. A local matching, based on a cross-correlation method, is performed on each pair of corresponding ROIs in order to determine shift values for the coordinates of two images. A proper warping of x,y coordinates is obtained by fitting two dimensional polynomials to the distributions of shift values. One of the images is warped and then subtracted from the other. Forty six pairs of chest images (42 with interval changes and 4 without interval change) were processed using this method. The subtraction images were able to enhance various important interval changes, such as differences in the size of tumor masses, changes in heart size, and changes in pulmonary infiltrates or pleural effusions. Approximately 70% of the pairs showed reasonably good registration. PMID- 8208222 TI - Resolution properties of a 2048 x 2048 matrix image intensifier-TV based digital radiography system. AB - Spatial resolution properties of a 2048 x 2048 matrix image intensifier (II) TV based real-time digital radiography (DR) system were investigated. The presampling modulation transfer function (MTF), which includes the unsharpness of the detector and the blurring effect of the sampling aperture, was measured by a slit method. Also determined was the limiting resolution using a bar pattern. It was found that, the spatial resolution in this system is substantially improved relative to previous II-TV based DR systems, and is comparable or even superior to that in a computed radiography system depending on the imaging plate employed. However, the presampling MTF for 2048 x 2048 matrix is comparable to that for 1024 x 1024 matrix in this DR system, because the same sampling aperture is assumed to be used for both matrices. Even under these conditions obtained the improved clinical image since the Nyquist frequency is doubled for 2048 x 2048 matrix. It should be noted that the resolution property in the II-TV based DR system depends on the signal current from the TV image pickup tube (level of image pixel value) and also on the size of the iris in the TV lens. We must pay attention to these parameters when acquiring clinical images and evaluating the resolution properties. Finally, it was demonstrated that smaller focus than that used in a screen-film system can be employed in the DR system due to its high sensitivity, so the geometric unsharpness can be reduced. Therefore, the image resolution of our system was found to be superior to a screen-film system at some geometric magnification factors. PMID- 8208223 TI - The x-ray fovea, a device for reducing x-ray dose in fluoroscopy. AB - The x-ray fovea (U.S. patents pending) is a device for reducing x-ray dose to patients and operations during x-ray fluoroscopy. It consists of a semitransparent collimator with an open, circular, central hole. The fovea collimator is placed at the exit of the x-ray tube, and the attenuation of the peripheral x-ray beam reduces x-ray exposure to patients and operators. The shadow caused by the x-ray fovea can be compensated using real-time image processing hardware. Accurate compensation is demonstrated for both linearly and logarithmically acquired images using a model that accounts for beam hardening in the fovea collimator. The central fovea region has improved image quality due to reduced scatter and veiling glare from the periphery. From beam-stop measurements, a 40% reduction in scatter plus veiling glare is measured using the fovea. A contrast improvement ratio of 1.5 is measured throughout the central region. In the compensated periphery, noise is increased by a factor of 1.66 because fewer photons are detected, but a small amount of temporal filtering compensates this degradation. The Roentgen area product (RAP) exposure to patients is reduced by approximately 70%, while scattered exposure to operators is reduced by approximately 60%. PMID- 8208225 TI - An overview of Canada's mental health system. AB - In summary, the Canadian health system is an outstanding success, as far as its consumers are concerned. Increasing costs are generally considered to be grounded in factors that could be, and are being, remedied. Health insurance also works very well for that segment of the mental health system that requires intervention by psychiatrists in office or general hospital practice. Unfortunately, certain decisions that were made during the development of the health insurance system have created obstacles to the provision of adequate services to the chronically mentally ill. However, these systemic ailments, which are now being addressed in most provinces, do not seem to have been fatal. PMID- 8208224 TI - Computing the modulation transfer function of a magnetic resonance imager. AB - A new method for computing the modulation transfer function (MTF) of magnetic resonance (MR) imagers is presented. Previous attempts to compute the MTF of MR images used nonlinear magnitude reconstructed images, resulting in erroneous MTFs. By using complex domain images, the new method produces predisplay MTFs which describe the spatial frequency transfer characteristics of the entire image formation process, except the magnitude operator, eliminating the artifacts previously found in MR imager MTFs. The use of complex domain images results in two-sided MTFs which differentiate the positive and negative frequencies associated with positive and negative phase encoding or positive and negative time relative to the echo formation. Experimental results are presented which confirm the theoretically predicted form of MR imager MTFs and the need for two sided MTFs. PMID- 8208226 TI - Planning mental health services: background and key issues. AB - Deinstitutionalization in Canada produced a shift in locus of care from provincial psychiatric hospitals to general hospital psychiatric units. As a result of this approach, a number of key planning issues have emerged that most provinces are attempting to address. PMID- 8208227 TI - Deinstitutionalization and service priorities in Canada and the United States. PMID- 8208228 TI - Planning mental health services: current Canadian initiatives. PMID- 8208229 TI - Mental health policy in Quebec: challenges for an integrated system. PMID- 8208230 TI - Serving severely mentally ill people in a major Canadian city. AB - Over the past twenty years, GVMHS has been the single organization taking ultimate responsibility for the seriously mentally ill throughout the city. It uses central coordination coupled with community-based teams and partnership programs with other agencies to strike a useful balance between integration and flexibility. GVMHS's mission throughout that time has been to provide everyday community support, networking, case management, rehabilitation, and counseling services to as many seriously mentally ill persons with concomitant disabilities as possible. To carry out that mission, GVMHS has developed some innovative solutions for the problems of community support--problems such as psychiatric emergencies, crises, community demands for service outside the mandate, and workload management. GVMHS has also developed dual-diagnosis, multicultural, multiagency case coordination for the multiproblem client (Buckley and Bigelow, 1992), specialized family and child programs, and specialized geriatric programs. This has all been possible only because financial support is available on an ongoing basis at a level adequate to provide good, dependable services. GVMHS has been proven an effective service in a number of studies (Bigelow and Beiser, 1978; Beiser, Shore, Peters, and Tatum, 1985). It has also demonstrated good cost efficiency (Bigelow and McFarland, 1989) and abundant innovation and adaptation to emerging challenges (Bigelow, McFarland, Russell, and Sladen-Dew, 1990). It has proven that dedicated, well-trained professionals working at the community level will work hard and smart and that an agency and its staff will stick to the mandate of serving people with serious mental illnesses and disabilities even under pressure to do otherwise. The intriguing thing is that this productivity is not driven by competition, incentives, or threat: none of these factors presses upon the Greater Vancouver Mental Health Services Society from without and none is built in. The excellent performance of GVMHS seems to derive from the professional dedication and motivation of the clinical staff and its administration. PMID- 8208231 TI - Financing Canada's mental health services. PMID- 8208232 TI - Mental health of immigrants and refugees. PMID- 8208233 TI - Reflections on mental health service delivery in Canada: one American's view. PMID- 8208234 TI - Heat-related deaths--Philadelphia and United States, 1993-1994. AB - During June 1994, temperatures across the United States were higher than usual. Since June 13, record high temperatures (above 90 F [32.2 C]) with humidities of 50%-60% have occurred in the northeastern United States (1). During July 1-14, 1993, the eastern United States also experienced a severe heat wave with high temperatures (93 F-101 F [33.9 C-38.3 C]) and high humidity (36%-58%) (2). During July 6-14, 1993, in Philadelphia, medical examiners (MEs) determined 118 deaths were heat-related*. This report describes heat-related deaths that occurred in Philadelphia during 1993 and 1994 and summarizes risk factors for heat-related illness and death. PMID- 8208235 TI - Human rabies--California, 1994. AB - In January 1994, a 44-year-old California man died from a bat-associated strain of rabies; he had had no known animal bite or other rabies exposure. Rabies was not clinically suspected nor confirmed until 1 month after his death. This report summarizes the case investigation. PMID- 8208236 TI - Outbreak of measles among Christian Science students--Missouri and Illinois, 1994. AB - During April 4-May 17, 1994, the largest U.S. measles outbreak since 1992 occurred among students in two communities that do not routinely accept vaccination. This report summarizes the investigation of and control measures for this outbreak. PMID- 8208237 TI - Update: external cause-of-injury coding in hospital discharge data--United States, 1994. AB - Although analysis of hospital discharge data (HDD) can provide important information about severe nonfatal injuries, HDD often do not include information about the causes of these injuries (e.g., motor-vehicle crashes and assaults). Inconsistent reporting of causes of injury has limited the usefulness of HDD for injury surveillance. The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) includes codes for classifying external causes of injury (E-codes). This report describes progress in implementing E-code reporting in states. PMID- 8208238 TI - Surveillance for smoking-attributable mortality and years of potential life lost, by state--United States, 1990. AB - PROBLEM/CONDITION: Mortality and years of potential life lost attributable to cigarette smoking. REPORTING PERIOD COVERED: 1990. DESCRIPTION OF SYSTEM: Mortality and years of potential life lost were estimated for each state by using the Smoking-Attributable Mortality, Morbidity, and Economic Costs (SAMMEC) software. These estimates were based on attributable risk formulas for smoking related causes of death. Estimates of smoking prevalence were obtained from the Behavioral Risk Factor Surveillance System and the U.S. Bureau of the Census, and mortality data were obtained from CDC. RESULTS: The median estimate for the number of smoking-attributable deaths among states was 5,619 (range: 402 [Alaska] to 42,574 [California]). Within each state, the number of smoking-attributable deaths among males was approximately twice as high as among females. Utah had the lowest mortality rate (218.0 per 100,000 population) and the lowest percentage of all deaths attributable to cigarette smoking (13.4%). Nevada had the highest mortality rate (478.1 per 100,000 population) and the highest percentage of deaths from smoking (24.0%). The number of years of potential life lost ranged from 6,720 (Alaska) to 498,297 (California). INTERPRETATION: The number of deaths attributable to cigarette smoking in 1990 remained high. Efforts are needed to control tobacco use in all states. ACTIONS TAKEN: SAMMEC data are used in many states to assist policymakers in strengthening tobacco control efforts. PMID- 8208239 TI - Surveillance for occupational asthma--Michigan and New Jersey, 1988-1992. AB - PROBLEM/CONDITION: A case of occupational asthma is a sentinel health event indicating a need for preventive intervention. REPORTING PERIOD COVERED: 1988 1992. DESCRIPTION OF SYSTEMS: As part of the Sentinel Event Notification System for Occupational Risks (SENSOR) Program, initiated by CDC's National Institute for Occupational Safety and Health in 1987, state-based surveillance and intervention programs for occupational asthma (OA) have been under development in Michigan and New Jersey. The initial 5-year projects in these states have been completed. RESULTS: From 1988 through 1992, the SENSOR programs in these states identified a total of 535 cases of occupational asthma and related conditions. Of these 535 cases, 328 cases met the SENSOR surveillance case definition for OA. In addition, 128 cases were classified as possible OA, 42 as reactive airways dysfunction syndrome, and 37 as occupationally aggravated asthma. In both Michigan and New Jersey, manufacturing was the industrial sector with the largest proportion of cases. In Michigan, > 40% of the case-patients worked in transportation equipment manufacturing. In New Jersey, 15% of case-patients worked in manufacturing of chemicals and allied products. Overall, isocyanates were the most frequently reported asthma-causing agents (19.4% of cases). Follow up industrial hygiene sampling measured suspect agents at airborne concentrations generally below the permissible exposure limits established by the Occupational Safety and Health Administration. INTERPRETATION: In its first 5 years, the SENSOR system has led to the identification of previously unrecognized causes of occupational asthma. Overall findings indicate the need for more comprehensive control of such well-known occupational allergens as the isocyanates. In addition, SENSOR interventions have prompted improvements in protection for workers. ACTIONS TAKEN: Approaches to state-based surveillance and intervention for OA are being developed through newly funded 5-year SENSOR projects in four states (California, Massachusetts, Michigan, and New Jersey). The goal is to develop a model for effective state-based OA surveillance that can be applied by any state health department. PMID- 8208240 TI - The positive and negative cis-acting elements for methanol regulation in the Pichia pastoris AOX2 gene. AB - The methylotrophic yeast Pichia pastoris has two alcohol oxidase genes, AOX1 and AOX2. The AOX2 gene is transcribed at a much lower level than the AOX1 gene. Apart from this difference in expression levels, the two genes are regulated similarly. To study the role of cis-acting elements in the promoter region of the AOX2 gene, we constructed expression plasmids in which the human serum albumin (HSA) gene was placed under the control of various deleted or mutated AOX2 promoter derivatives. By analyzing the expression of HSA in P. pastoris transformants, we have identified three cis-acting regulatory elements in the AOX2 promoter. The positive cis-acting element AOX2-UAS, located between positions -337 and -313 (relative to the transcription initiation codon), is required for response to transcriptional induction by methanol in an orientation independent manner, and artificial amplification of the AOX2-UAS resulted in an increase in the transcriptional activity of the promoter. A sequence homologous to AOX2-UAS was also found in the AOX1 promoter, and in methanol-regulated promoters in other methylotrophic yeast. Two negative cis-acting elements, AOX2 URS1 and AOX2-URS2 play a role in repressing transcription from the AOX2 promoter. The function of AOX2-UAS is completely repressed by this unique repression system when both the AOX2-URS1 and AOX2-URS2 are functional. PMID- 8208241 TI - Hydrogen peroxide induces G:C to T:A and G:C to C:G transversions in the supF gene of Escherichia coli. AB - A vector plasmid, pZ189, carrying an Escherichia coli supF gene as a target for mutations, was treated with a combination of hydrogen peroxide and Fe3+/EDTA complex and propagated in E. coli host cells that had been induced for SOS functions by ultraviolet irradiation. The mutations frequency increased by up to 30-fold over spontaneous background levels with increasing concentrations of hydrogen peroxide. The increase in mutation frequency correlated with an increase in the formation of 8-hydroxydeoxyguanosine in the pZ189 DNA. Sequence analysis of 82 independent supF mutant plasmids revealed that 70 mutants contained base substitutions, with 63 of the 70 involving a G:C base pair, and with G:C-->C:G (28 cases) and G:C-->T:A (26 cases) transversions predominating. Investigation of the influence of the local DNA sequence on the transversions revealed that the guanine at the center of the triplet 5'-PuGA-3' was five times more likely to mutate after treatment with hydrogen peroxide than that at the center of 5'PyGN3'. G:C-->T:A transversions presumably resulted from mispairing of an altered G (probably 8-hydroxydeoxyguanosine) with deoxyadenosine. The origin of the G:C-->C:G transversions may be an as yet unidentified lesion generated by hydrogen peroxide. Mutagenic hotspots for base substitutions were found at positions 133, 160 and 168. Mutation spectra and the positions of mutagenic hotspots, when compared with a previously determined spontaneous mutagenesis spectrum, also provide information on the mechanism of spontaneous mutagenesis. PMID- 8208242 TI - A gene from the fungal plant pathogen Nectria haematococca that encodes the phytoalexin-detoxifying enzyme pisatin demethylase defines a new cytochrome P450 family. AB - The gene PDAT9 from the fungus Nectria haematococca encodes pisatin demethylase, an enzyme that detoxifies the phytoalexin pisatin, an antimicrobial compound produced by pea in response to infection by this plant pathogen. PDAT9 was found to contain an open reading frame (ORF) encoding 515 amino acids and four introns of 52-58 nucleotides each within its coding region. The amino acid sequence F-G-A G-S-R-S-C-I-G, indicative of the "fifth ligand binding site" present in all cytochrome P450s, occurs as residues 446 to 455, confirming that PDAT9 is a cytochrome P450. The deduced amino acid sequence is distinct from all other reported cytochrome P-450s, and PDAT9 has been assigned to a new cytochrome P450 family, CYP57. A 1.3 kb SacI fragment of the PDAT9 ORF that lacked the fifth ligand binding site, hybridized to unique DNA fragments in N. haematococca isolates known to possess PDA genes that encode different whole cell phenotypes for pisatin demethylating activity. These genes were also tentatively identified as cytochrome P450s by the hybridization of the same fragments to separate subclones of PDAT9, one of which contained the fifth ligand sequence. That probe also hybridized to DNA other than that attributed to pisatin demethylase genes; these other DNAs are presumed to represent other cytochrome P450s. PMID- 8208243 TI - Isolation of a gene (pbsC) required for siderophore biosynthesis in fluorescent Pseudomonas sp. strain M114. AB - An iron-regulated gene, pbsC, required for siderophore production in fluorescent Pseudomonas sp. strain M114 has been identified. A kanamycin-resistance cassette was inserted at specific restriction sites within a 7 kb genomic fragment of M114 DNA and by marker exchange two siderophore-negative mutants, designated M1 and M2, were isolated. The nucleotide sequence of approximately 4 kb of the region flanking the insertion sites was determined and a large open reading frame (ORF) extending for 2409 bp was identified. This gene was designated pbsC (pseudobactin synthesis C) and its putative protein product termed PbsC. PbsC was found to be homologous to a family of enzymes involved in the biosynthesis of secondary metabolites, including EntF of Escherichia coli. These enzymes are believed to act via ATP-dependent binding of AMP to their substrate. Several areas of high sequence homology between these proteins and PbsC were observed, including a conserved AMP-binding domain. The expression of pbsC is iron-regulated as revealed when a DNA fragment containing the upstream region was cloned in a promoter probe vector and conjugated into the wild-type strain, M114. The nucleotide sequence upstream of the putative translational start site contains a region homologous to previously defined -16 to -25 sequences of iron-regulated genes but did not contain an iron-box consensus sequence. It was noted that inactivation of the pbsC gene also affected other iron-regulated phenotypes of Pseudomonas M114. PMID- 8208244 TI - Structure of the 5' upstream region and the regulation of the rpoS gene of Escherichia coli. AB - The nucleotide sequence of the 5' upstream region of the Escherichia coli rpoS gene was determined and analyzed. At least four promoters responsible for rpoS transcription were identified, and designated P1, P2, P3 and P4, P1 being furthest from the upstream. Using lacZ fusion genes, the P2 promoter was found to be the strongest of the four. All of these promoters are regulated similarly, and their activity is enhanced 2 to 3-fold in stationary phase. P1 and P2 transcription start sites were determined by primer extension analyses. The P2 promoter region shows similarity to the consensus sigma 70-type promoter sequence, and was recognized by both E sigma 70 and E sigma 38 holoenzymes in vitro. The mRNA transcribed from the most distal promoter, P1, appears to include another open reading frame (orf-281), indicating that the two open reading frames comprise an operon. The rpoS gene product (sigma 38) was rapidly degraded after addition of chloramphenicol to cultures in the exponential, but not the stationary phase. This strongly suggests that posttranslational regulation is involved in the control of rpoS expression. PMID- 8208245 TI - Ogura cytoplasmic male-sterility (CMS)-associated orf138 is translated into a mitochondrial membrane polypeptide in male-sterile Brassica cybrids. AB - Transcription of a putative mitochondrial gene (orf138) has previously been correlated with Ogura cytoplasmic male-sterility (CMS) in rapeseed cybrids. In this paper, studies performed on a Brassica cybrid with a different organization of the orf138 locus confirm this association. We also show that mitochondria isolated from male-sterile rapeseed plants synthesize a polypeptide of 19 kDa, which is absent in fertile revertants. Antibodies against a glutathione S transferase-ORF138 fusion protein were raised to establish that this 19 kDa polypeptide is the product of orf138. The anti-ORF138 serum was used to demonstrate that the orf138 translation product occurs only in sterile cybrids and co-purifies with the mitochondrial membrane fraction. PMID- 8208246 TI - Transcriptional activation of a cycloheximide-inducible gene encoding laccase is mediated by cpc-1, the cross-pathway control gene, in Neurospora crassa. AB - Expression of the laccase gene (lacc) of Neurospora crassa is transcriptionally inducible by the protein synthesis inhibitor cycloheximide. A lni-1 mutation, conferring the laccase non-inducible phenotype, was found to be a cpc-1 allele. Northern blots probed with plasmid pLA1, which carries the lacc gene revealed that the cpc-1 mutation abolishes the induced transcription of the lacc gene, indicating requirement of the cpc-1 gene for transcriptional activation of the lacc gene. In Northern blots probed with plasmid pAB1, which bears arg-2 a gene whose transcription is under the control of CPC1, the level of the arg-2 transcript was shown to increase several-fold in wild-type mycelia but remained low in cpc-1 mycelia, after treatment with cycloheximide. This suggests that inhibition of protein synthesis with cycloheximide, as well as amino acid limitation, elicits the CPC1-mediated cross-pathway control. Characterization of the lacc upstream region using a series of 5'-deletion plasmids led to the identification of a 170 bp DNA region required for the induced lacc expression. Sequence analysis of this DNA region demonstrated that it includes a 9 bp sequence with dyad symmetry, ATGAATCAT, which differs only by a central base pair from ATGA(C/G)TCAT, the recognition sequence characteristic of CPC1 and GCN4 binding sites. Possible mechanisms by which CPC1 mediates transcriptional activation of the lacc gene are discussed. PMID- 8208247 TI - Drosophila GABAergic systems. II. Mutational analysis of chromosomal segment 64AB, a region containing the glutamic acid decarboxylase gene. AB - The Drosophila melanogaster Gad gene maps to region 64A3-5 of chromosome 3L and encodes glutamic acid decarboxylase (GAD), the rate-limiting enzyme for the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Because this neurotransmitter has been implicated in developmental functions, we have begun to study the role of GABA synthesis during Drosophila embryogenesis. We show that Gad mRNA is expressed in a widespread pattern within the embryonic nervous system. Similarly, GAD-immunoreactive protein is present during embryogenesis. These results prompted us to screen for embryonic lethal mutations that affect GAD activity. The chromosomal region to which Gad maps, however, has not been subjected to an extensive mutational analysis, even though it contains several genes encoding important neurobiological, developmental, or cellular functions. Therefore, we have initially generated both chromosomal rearrangements and point mutations that map to the Drosophila 64AB interval. Altogether, a total of 33 rearrangements and putative point mutations were identified within region 64A3-5 to 64B12. Genetic complementation analysis suggests that this cytogenetic interval contains a minimum of 19 essential genes. Within our collection of lethal mutations are several chromosomal rearrangements, two of which are in the vicinity of the Gad locus. One of these rearrangements, Df(3L)C175, is a small deletion that removes the Gad locus and at least two essential genes; the second, T(2;3)F10, is a reciprocal translocation involving the second and third chromosomes with a break within region 64A3-5. Both of these rearrangements are associated with embryonic lethality and decreased GAD enzymatic activity. PMID- 8208248 TI - MBR1 and MBR3, two related yeast genes that can suppress the growth defect of hap2, hap3 and hap4 mutants. AB - Two new yeast genes, named MBR1 and MBR3, were isolated as multicopy suppressors of the growth defect of a strain lacking the HAP2 transcriptional activator. Both genes when overexpressed can also suppress the growth defect of hap3 and hap4 null mutants. However, overexpression of MBR1 cannot substitute for the HAP2/3/4 complex in activation of the CYC1 gene. Nucleotide sequencing of MBR1 and MBR3 revealed that these two genes encode serine-rich, hydrophilic proteins with regions of significant homology. The functional importance of one of these conserved regions was shown by mutagenesis. Disruption of MBR1 leads to a partial growth defect on glycerol medium. Disruption of MBR3 has no major effect but the double disruptant shows a synthetic phenotype suggesting that the MBR1 and MBR3 gene products participate in common function. PMID- 8208249 TI - Different UmuC requirements for generation of different kinds of UV-induced mutations in Escherichia coli. AB - An Escherichia coli strain bearing the dnaQ49 mutation, which results in a defective epsilon subunit of DNA polymerase III, and carrying the lexA71 mutation, which causes derepression of the SOS regulon, is totally unable to maintain high-copy-number plasmids containing the umuDC operon. The strain is also unable to maintain the pAN4 plasmid containing a partial deletion of the umuD gene but retaining the wild-type umuC gene. These results suggest that a high cellular level of UmuC is exceptionally harmful to the defective DNA polymerase III of the dnaQ49 mutant. We have used this finding as a basis for selection of new plasmid umuC mutants. The properties of two such mutants, bearing the umuC61 or umuC95 mutation, are described in detail. In the umuC122::Tn5 strain harbouring the mutant plasmids, UV-induced mutagenesis is severely decreased compared to that observed with the parental umuDC+ plasmid. Interestingly, while the frequency of UV-induced GC-->AT transitions is greatly reduced, the frequency of AT-->TA transversions is not affected. Both mutant plasmids bear frameshift mutations within the same run of seven A residues present in umuC+; in umuC61 the run is shortened to six A whereas in umuC95 is lengthened to eight A. We have found in both umuC61 and umuC95 that translation is partially restored to the proper reading frame. We propose that under conditions of limiting amounts of UmuC, the protein preferentially facilitates processing of only some kinds of UV-induced lesions. PMID- 8208250 TI - Cloning and analysis of DNA sequences from Streptomyces hygroscopicus encoding geldanamycin biosynthesis. AB - A gene library constructed from large (approximately 20 kb) fragments of total DNA from the geldananmycin-producing strain Streptomyces hygroscopicus 3602 cloned in the plasmid vector pIJ61 were used to transform S. lividans TK24. Three transformants of about 800 tested were found to have acquired the ability to produce an antibiotic lethal to a geldanamycin-sensitive strain of Bacillus subtilis. The plasmids isolated from these transformants, pIA101, pIA102 and pIA103, each contained an insert of approximately 15 kb. A 4.5 kb DNA fragment from the insert in pIA102 hybridised to DNA from S. hygroscopicus 3602 and to DNA encoding part of the erythromycin polyketide synthase but not to S. lividans TK24 DNA. The integration-defective phage vector phi C31 KC515 containing this 4.5 kb fragment was able to lysogenise S. hygroscopicus 3602 to produce lysogens defective in geldanamycin production. Loss of the prophage restored the ability to produce geldanamycin. Extracts of fermentation broth cultures of S. lividans containing pIA101, pIA102 and pIA102 and pIA103 analysed by thin-layer chromatography (TLC) contained compounds identical or very similar to purified geldanamycin, which were not present in S. lividans. These compounds showed a mass spectrum indistinguishable from geldanamycin. The evidence suggests that the clones contain DNA sequences encoding functions required for geldanamycin biosynthesis including components of the polyketide synthase. PMID- 8208251 TI - The smallest known eukaryotic genomes encode a protein gene: towards an understanding of nucleomorph functions. AB - Cryptomonads are unicellular algae with plastids surrounded by four membranes. Between the two pairs of membranes lies a periplastidal compartment that harbours a DNA-containing organelle, termed the nucleomorph. The nucleomorph is the vestigial nucleus of a phototrophic, eukaryotic endosymbiont. Subcloning of parts of one nucleomorph chromosome revealed a gene coding for an Hsp70 protein. We demonstrate the expression of this nucleomorph protein-coding gene and present a model for protein transport from the host to the endosymbiont compartment. PMID- 8208252 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 27-1994. A 41-year-old woman with neurologic abnormalities and an osteolytic lesion in the mandible. PMID- 8208253 TI - Magnetic resonance imaging of the lumbar spine. Terrific test or tar baby? PMID- 8208254 TI - bcl-6 in lymphoma--sorting out a wastebasket? PMID- 8208255 TI - The war on drugs. PMID- 8208256 TI - The war on drugs. PMID- 8208257 TI - The war on drugs. PMID- 8208258 TI - The war on drugs. PMID- 8208259 TI - The war on drugs. PMID- 8208260 TI - Resistance to activated protein C. PMID- 8208261 TI - Resistance to activated protein C. PMID- 8208262 TI - Hyperandrogenism in polycystic ovary syndrome. PMID- 8208263 TI - Urinary pyridinium cross-links: a noninvasive diagnostic test for Ehlers-Danlos syndrome type VI. PMID- 8208264 TI - Membranous nephropathy and a TAP1 gene polymorphism. PMID- 8208265 TI - More on the declining age at HIV infection. PMID- 8208266 TI - Hepatotoxicity of saccharin. PMID- 8208267 TI - Magnetic resonance imaging of the lumbar spine in people without back pain. AB - BACKGROUND: The relation between abnormalities in the lumbar spine and low back pain is controversial. We examined the prevalence of abnormal findings on magnetic resonance imaging (MRI) scans of the lumbar spine in people without back pain. METHODS: We performed MRI examinations on 98 asymptomatic people. The scans were read independently by two neuroradiologists who did not know the clinical status of the subjects. To reduce the possibility of bias in interpreting the studies, abnormal MRI scans from 27 people with back pain were mixed randomly with the scans from the asymptomatic people. We used the following standardized terms to classify the five intervertebral disks in the lumbosacral spine: normal, bulge (circumferential symmetric extension of the disk beyond the interspace), protrusion (focal or asymmetric extension of the disk beyond the interspace), and extrusion (more extreme extension of the disk beyond the interspace). Nonintervertebral disk abnormalities, such as facet arthropathy, were also documented. RESULTS: Thirty-six percent of the 98 asymptomatic subjects had normal disks at all levels. With the results of the two readings averaged, 52 percent of the subjects had a bulge at at least one level, 27 percent had a protrusion, and 1 percent had an extrusion. Thirty-eight percent had an abnormality of more than one intervertebral disk. The prevalence of bulges, but not of protrusions, increased with age. The most common nonintervertebral disk abnormalities were Schmorl's nodes (herniation of the disk into the vertebral body end plate), found in 19 percent of the subjects; annular defects (disruption of the outer fibrous ring of the disk), in 14 percent; and facet arthropathy (degenerative disease of the posterior articular processes of the vertebrae), in 8 percent. The findings were similar in men and women. CONCLUSIONS: On MRI examination of the lumbar spine, many people without back pain have disk bulges or protrusions but not extrusions. Given the high prevalence of these findings and of back pain, the discovery by MRI of bulges or protrusions in people with low back pain may frequently be coincidental. PMID- 8208268 TI - Rearrangement of the bcl-6 gene as a prognostic marker in diffuse large-cell lymphoma. AB - BACKGROUND: About 40 percent of non-Hodgkin's lymphomas are diffuse lymphomas with a large-cell component (DLLC). Current therapy can induce a long-term remission in half the patients with DLLC, but more intensive treatment has the potential to improve outcome, particularly in patients at high risk for treatment failure. Clinical and cytogenetic markers can identify subgroups at high or low risk. Rearrangement of a novel candidate proto-oncogene, bcl-6, is a possible prognostic indicator in DLLC. METHODS: We performed Southern blot hybridization to detect bcl-6 and bcl-2 gene rearrangement in samples of lymphoma from 102 patients with B-cell DLLC. The results were correlated with the patients' histologic features, age, disease stage, tumor sites and bulk of disease, serum lactate dehydrogenase level, and treatment outcome. RESULTS: Rearranged bcl-6 was found in 23 cases, and rearranged bcl-2 in 21 cases. Nineteen of the patients with rearranged bcl-6 had extranodal DLLC, two had primary splenic lymphomas, and only one had bone marrow involvement. Thirty-six months after diagnosis, the proportion with freedom from progression of disease was projected to be 82 percent (95 percent confidence interval, 66 to 98 percent) among the patients with rearranged bcl-6, as compared with 56 percent (95 percent confidence interval, 43 to 70 percent) for the patients with germ-line bcl-6 and bcl-2 and 31 percent (95 percent confidence interval, 8 to 53 percent) for the patients with rearranged bcl-2. The status of the bcl-6 gene was an independent prognostic marker of survival and freedom from disease progression in a multivariate model and added predictive value to established prognostic signs. CONCLUSIONS: Rearrangement of the bcl-6 gene correlated with a favorable clinical outcome in DLLC and may thus serve as a prognostic marker in patients with this form of malignant lymphoma. PMID- 8208269 TI - Diabetes and the risk of pancreatic cancer. AB - BACKGROUND: Diabetes and pancreatic cancer are known to be associated, but the cause of the association and whether diabetes is a risk factor for pancreatic cancer remain controversial. METHODS: A total of 720 patients with pancreatic cancer and 720 control patients from 14 Italian centers were enrolled in the study. All subjects were interviewed personally and in detail about their clinical history. The diagnosis of diabetes was based on criteria recommended by the American Diabetes Association. RESULTS: One hundred sixty-four patients with pancreatic cancer (22.8 percent) and 60 controls (8.3 percent) had diabetes. In the majority of the patients with pancreatic cancer (56.1 percent), diabetes was diagnosed either concomitantly with the cancer (in 40.2 percent), or within two years before the diagnosis of cancer (in 15.9 percent). The association between the two conditions was significant (odds ratio, 3.04; 95 percent confidence interval, 2.21 to 4.17). However, when only patients with diabetes of three or more years' duration were considered, the association was no longer significant (odds ratio, 1.43; 95 percent confidence interval, 0.98 to 2.07). All the patients with pancreatic cancer whose diabetes had been diagnosed before the cancer had non-insulin-dependent diabetes; all but one of the control patients with diabetes had the non-insulin-dependent form of the disease. CONCLUSIONS: Diabetes in patients with pancreatic cancer is frequently of recent onset and is presumably caused by the tumor. Diabetes is not a risk factor for pancreatic cancer. PMID- 8208270 TI - Brief report: successful treatment of disseminated acanthamoeba infection in an immunocompromised patient. PMID- 8208271 TI - Images in clinical medicine. Wallerian degeneration of the pyramidal tract. PMID- 8208272 TI - Attitudes toward assisted suicide and euthanasia among physicians in Washington State. AB - BACKGROUND: Despite considerable public interest in legalizing physician-assisted suicide and euthanasia, little is known about physicians' attitudes toward these practices. METHODS: We sent questionnaires to 1355 randomly selected physicians in the state of Washington, including all hematologists and oncologists and a disproportionately high number of internists, family practitioners, psychiatrists, and general surgeons. To avoid ambiguity in our survey, instead of "physician-assisted suicide," we used the phrase "prescription of medication [e.g., narcotics or barbiturates] or the counseling of an ill patient so he or she may use an overdose to end his or her own life." Instead of "euthanasia," we used the phrase "deliberate administration of an overdose of medication to an ill patient at his or her request with the primary intent to end his or her life." RESULTS: Of the 1355 eligible physicians who received our questionnaire, 938 (69 percent) responded. Forty-eight percent of the respondents agreed with the statement that euthanasia is never ethically justified, and 42 percent disagreed. Fifty-four percent thought euthanasia should be legal in some situations, but only 33 percent stated that they would be willing to perform euthanasia. Thirty nine percent of respondents agreed with the statement that physician-assisted suicide is never ethically justified, and 50 percent disagreed. Fifty-three percent thought assisted suicide should be legal in some situations, but only 40 percent stated that they would be willing to assist a patient in committing suicide. Of the groups surveyed, hematologists and oncologists were most likely to oppose euthanasia and assisted suicide, and psychiatrists were most likely to support these practices. CONCLUSIONS: The attitudes toward physician-assisted suicide and euthanasia of physicians in Washington State are polarized. A slight majority favors legalizing physician-assisted suicide and euthanasia in at least some situations, but most would be unwilling to participate in these practices themselves. PMID- 8208273 TI - Diseases of the retina. PMID- 8208274 TI - US puts large-scale AIDS vaccine trials on ice as 'premature'. PMID- 8208275 TI - Court orders DNA test over chemical claims. PMID- 8208276 TI - Trials 'must compete for new funds'. PMID- 8208278 TI - Lords fail to reverse move to ban embryo treatment. PMID- 8208277 TI - Double helix goes on public display. PMID- 8208279 TI - NCI restores funding to gene therapist seen as 'too hasty'. PMID- 8208280 TI - Compromise reached on bioethics bill. PMID- 8208281 TI - European brain research. PMID- 8208282 TI - No hitch-hikers. PMID- 8208283 TI - If it ain't fixed, don't break it.... AB - Value-judgements about the need for more 'goal-directed' or 'basic' scientific research beg the question of how the publicly funded scientific enterprise works. An efficient management would start to put things right. PMID- 8208284 TI - RNA processing. Cycling splicing factors. PMID- 8208285 TI - Immunology. Memories are made of this? PMID- 8208286 TI - G proteins. The importance of being GTP. PMID- 8208287 TI - DNA recognition and the code. PMID- 8208288 TI - Pore region of K+ channel RACTK1. PMID- 8208289 TI - Structural determinants for activation of the alpha-subunit of a heterotrimeric G protein. AB - The 1.8 A crystal structure of transducin alpha.GDP, when compared to that of the activated complex with GTP-gamma S, reveals the nature of the conformational changes that occur on activation of a heterotrimeric G-protein alpha-subunit. Structural changes initiated by direct contacts with the terminal phosphate of GTP propagate to regions that have been implicated in effector activation. The changes are distinct from those observed in other members of the GTPase superfamily. PMID- 8208290 TI - Implications of early hominid labyrinthine morphology for evolution of human bipedal locomotion. AB - The upright posture and obligatory bipedalism of modern humans are unique among living primates. The evolutionary history of this behaviour has traditionally been pursued by functional analysis of the postcranial skeleton and the preserved footprint trails of fossil hominids. Here we report a systematic attempt to reconstruct the locomotor behaviour of early hominids by looking at a major component of the mechanism for the unconscious perception of movement, namely by examining the vestibular system of living primates and early hominids. High resolution computed tomography was used to generate cross-sectional images of the bony labyrinth. Among the fossil hominids the earliest species to demonstrate the modern human morphology is Homo erectus. In contrast, the semicircular canal dimensions in crania from southern Africa attributed to Australopithecus and Paranthropus resemble those of the extant great apes. Among early Homo specimens, the canal dimensions of Stw 53 are unlike those seen in any of the hominids or great apes, whereas those of SK 847 are modern-human-like. PMID- 8208291 TI - Immunoglobulin synthesis and generalized autoimmunity in mice congenitally deficient in alpha beta(+) T cells. AB - Through cognate B-cell-T-cell interactions and provision of cytokines, CD4+ T cell antigen receptor (TCR) alpha beta+ T cells regulate immunoglobulin isotype synthesis. Murine IgG1 and IgE secretion is therefore substantially T-cell dependent, whereas IgM and IgG3 secretion is not. Here we report that in the absence of alpha beta T cells, B cells expand, differentiate and secrete copious amounts of antibodies of 'T-dependent' isotypes. Moreover, the antibodies are reactive towards self-antigens, as in patients with systemic lupus erythematosus, so autoantibodies of 'T-dependent' type can develop without the help of CD4+ alpha beta T cells. This phenotype is not evident in mice or humans that are congenitally deficient in specific alpha beta T-cell functions, but bears comparison with B-cell hyperactivity and autoimmunity in transplant rejection and in immunodeficiencies such as AIDS. PMID- 8208292 TI - Severe sensory and sympathetic deficits in mice lacking neurotrophin-3. AB - During development, neurotrophins help shape the nervous system by regulating neuronal survival and differentiation. Neurotrophin-3 (refs 1-5) is the most abundant neurotrophin during early development. Neurons responsive to neurotrophin-3 in vitro include primary sensory, sympathetic, motor, enteric, locus coeruleus, hippocampal and cerebellar neurons (ref. 9 for example). Here we report that mice lacking neurotrophin-3 have severe deficits in sensory and sympathetic populations. These mice lack muscle spindles and show abnormal limb positions. In contrast, motor neurons, the enteric nervous system, and the major anatomical regions of the central nervous system seem to develop normally. Comparisons with mutants deficient in other neurotrophins or their receptors indicate that some neurons require more than one neurotrophin during embryogenesis and suggest that neurotrophin-3 functions by binding receptors in addition to its primary receptor trkC (ref. 16). In particular, neurotrophin-3 is essential for survival of sympathetic and sensory neurons that later become dependent on nerve growth factor or brain-derived neurotrophic factor. PMID- 8208293 TI - Flower colour intensity depends on specialized cell shape controlled by a Myb related transcription factor. AB - Flower colour is determined primarily by the production of pigments, usually anthocyanins or carotenoids, but the shade and intensity of the colour are often changed by other factors such as vacuolar compounds, pH and metal ions. Pigmentation can also be affected by the shape of epidermal cells, especially those facing prospective pollinators. A conical shape is believed to increase the proportion of incident light that enters the epidermal cells, enhancing light absorption by the floral pigments, and thus the intensity of their colour. We have identified a gene (mixta) that affects the intensity of pigmentation of epidermal cells in Antirrhinum majus petals. The cells of the corolla lobes fail to differentiate into their normal conical form in mixta mutants. We have cloned the mixta gene by transposon tagging; its sequence reveals that it encodes a Myb related protein that probably participates in the transcriptional control of epidermal cell shape. PMID- 8208294 TI - Sp1/egr-like zinc-finger protein required for endoderm specification and germ layer formation in Drosophila. AB - Much of our present knowledge of the biological processes involved in pattern formation in Drosophila is derived from segmentation analysis. Comparatively little is known about the genetic requirement and mechanisms underlying the formation and separation of germ layers by morphogenetic movements during gastrulation. Here we show that the Drosophila gene huckebein (hkb), a member of the gap-gene class of segmentation genes, is required for germ-layer formation at blastoderm. Absence of the hkb product, an Sp1/egr-like zinc-finger protein, causes the ectodermal and mesodermal primordia to expand at the expense of endoderm anlagen. Conversely, ectopic expression of hkb inhibits the formation of the major gastrulation fold which gives rise to the mesoderm and prevents normal segmentation in the ectoderm. Thus, hkb is necessary for endoderm development and its activity defines spatial limits within the blastoderm embryo in which the germ layers are established. PMID- 8208295 TI - Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. AB - Physical associations between cyclins, viral oncogenes and tumour suppressor genes imply a central role for cyclins in growth control. Cyclin D1 was identified as a candidate oncogene (PRAD1) in tumour-specific DNA rearrangements and is suspected to be a contributor to several types of neoplasms including breast cancer. Cyclin D1 also rescues G1 cyclin-defective Saccharomyces cerevisiae, and is a growth-regulated gene. Despite evidence suggesting that cyclin D1 is an oncogene, its ability to transform cells directly in culture remains controversial. To evaluate its potential to deregulate growth in vivo in a physiologically relevant tissue we overexpressed cyclin D1 in mammary cells in transgenic mice. We report here that overexpression of cyclin D1 resulted in abnormal mammary cell proliferation including the development of mammary adenocarcinomas. We conclude that overexpression of cyclin D1 deregulates cell proliferation and can induce tumorigenic changes in mammary tissues, suggesting that cyclin D1 indeed plays an important oncogenic role in breast cancer. PMID- 8208296 TI - Solution structure of a pleckstrin-homology domain. AB - Pleckstrin, the major protein kinase C substrate of platelets, contains domains of about 100 amino acids at the amino and carboxy termini that have been found in a number of proteins, including serine/threonine kinases, GTPase-activating proteins, phospholipases and cytoskeletal proteins. These conserved sequences, termed pleckstrin-homology (PH) domains, are thought to be involved in signal transduction. But the details of the function and binding partners of the PH domains have not been characterized. Here we report the solution structure of the N-terminal pleckstrin-homology domain of pleckstrin determined using heteronuclear three-dimensional nuclear magnetic resonance spectroscopy. The structure consists of an up-and-down beta-barrel of seven antiparallel beta strands and a C-terminal amphiphilic alpha-helix that caps one end of the barrel. The overall topology of the domain is similar to that of the retinol-binding protein family of structures. PMID- 8208297 TI - Structure of the pleckstrin homology domain from beta-spectrin. AB - The 'pleckstrin homology' or PH domain is a 100-residue protein module. It is present in many kinases, different isoforms of phospholipase C, GTPase-activating proteins and nucleotide-exchange factors. Its function is not known, but many proteins that contain a PH domain interact with GTP-binding proteins. The PH domain in beta-adrenergic receptor kinase may be involved in binding to the beta gamma subunits of a trimeric G-protein. We report here the three-dimensional structure of the PH domain of the cytoskeletal protein spectrin using homonuclear nuclear magnetic resonance. The core of the molecule is an antiparallel beta sheet consisting of seven strands. The C terminus is folded into a long alpha helix, and another helix is present in one of the surface loops. The molecule is electrostatically polarized and contains a pocket which may be involved in the binding of a ligand. There is a distant relationship to the peptidyl-prolyl-cis trans-isomerase FKBP in which this pocket is involved in the binding of the macrocyclic compound FK506 (refs 8-11). PMID- 8208298 TI - A serine kinase regulates intracellular localization of splicing factors in the cell cycle. AB - Small nuclear ribonucleoprotein particles (snRNPs) and non-snRNP splicing factors containing a serine/arginine-rich domain (SR proteins) concentrate in 'speckles' in the nucleus of interphase cells. It is believed that nuclear speckles act as storage sites for splicing factors while splicing occurs on nascent transcripts. Splicing factors redistribute in response to transcription inhibition or viral infection, and nuclear speckles break down and reform as cells progress through mitosis. We have now identified and cloned a kinase, SRPK1, which is regulated by the cell cycle and is specific for SR proteins; this kinase is related to a Caenorhabditis elegans kinase and to the fission yeast kinase Dsk1 (ref. 7). SRPK1 specifically induces the disassembly of nuclear speckles, and a high level of SRPK1 inhibits splicing in vitro. Our results indicate that SRPK1 may have a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells, and the reorganization of nuclear speckles during mitosis. PMID- 8208299 TI - Long PCR. PMID- 8208300 TI - Isoflurane inhibits nicotinic acetylcholine receptor-mediated 22Na+ influx and muscarinic receptor-evoked cyclic GMP production in cultured bovine adrenal medullary cells. AB - The effects of isoflurane on 22Na+ influx, 45Ca2+ influx, catecholamine secretion and cyclic GMP production induced by three kinds of secretagogue (nicotinic agonists, veratridine and a high concentration of K+) have been investigated using cultured bovine adrenal medullary cells. (1) Isoflurane (1-6%) inhibited catecholamine secretion stimulated by carbachol, nicotine and dimethyl-4 phenylpiperazinium in a concentration-dependent manner. Isoflurane suppressed carbachol-evoked 22Na+ influx and 45Ca2+ influx at concentrations similar to those which suppressed catecholamine secretion. The inhibition of catecholamine secretion by isoflurane was not overcome by increasing the concentration of carbachol. (2) The inhibitory effects of isoflurane on veratridine-induced 22Na+ influx, 45Ca2+ influx and catecholamine secretion became evident when the concentration of isoflurane was raised to 4-6%, i.e. 2-3 fold higher than the concentrations (1-2%) employed clinically. (3) High K(+)-evoked 45Ca2+ influx and catecholamine secretion were not affected by isoflurane (1-6%). (4) Isoflurane (1 6%) attenuated the production of cyclic GMP caused by muscarine, but not that caused by atrial natriuretic peptide or by sodium nitroprusside. These results suggest that isoflurane, at clinical anesthetic concentrations, inhibits nicotinic acetylcholine receptor-mediated cell responses as well as muscarinic receptor-mediated cyclic GMP production in adrenal medullary cells. PMID- 8208301 TI - Increase in dopamine release from the nucleus accumbens in response to feeding: a model to study interactions between drugs and naturally activated dopaminergic neurons in the rat brain. AB - The aim of the present study was to investigate the interactions between the in vivo release of dopamine and certain drugs, during conditions of increased dopaminergic activity. Dopaminergic neurons in the nucleus accumbens were activated by feeding hungry rats. 48-96 h after implantation of a microdialysis probe 30 min food ingestion by hungry rats induced an immediate eating response that was accompanied with a reproducible and long-lasting increase in extracellular dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC). The effect of various drugs (infused into the nucleus accumbens via the microdialysis probe), on the extracellular levels of dopamine and DOPAC were recorded, and the effect of eating was determined. Infusion of 5 mumol/l nomifensine and 3.4 mmol/l calcium increased dopamine release respectively 5.4 and 2-fold but did not modify the eating related increase in dopamine and DOPAC release. Infusion (1 mumol/l) as well as intraperitoneal administration (20 mg/kg) of sulpiride induced an increase in basal dopamine release to 220 and 195% of controls, respectively. Both routes of sulpiride pretreatment enhanced the eating related increase in extracellular dopamine and DOPAC. The results of the sulpiride experiments indicate that a behaviorally induced stimulation of dopamine release is modified by autoinhibition. PMID- 8208302 TI - Renal response to amino acid infusion in rats: effect of dopamine receptor antagonists and benserazide. AB - Previously, we have found that feeding is a dominant factor controlling urinary dopamine excretion (UDA) in conscious rats (Muhlbauer and Osswald 1992). Since the renal response to feeding is also characterized by an increase in glomerular filtration rate (GFR), we wanted to investigate in a first step whether the feeding-induced elevations of GFR and UDA could be causally related phenomena. Therefore, we studied the influence of dopamine synthesis and dopamine receptor blockade on the renal response to amino acid infusion (AA) in thiopental anesthetized rats. AA infusion (n = 7) increased GFR by 33 +/- 7% (P < 0.001) and UDA by 87 +/- 19% (P < 0.001). In the presence of benserazide (BZD, n = 5), an inhibitor of dopamine synthesis, infused i.v. at a dose of 30 micrograms/min/kg, UDA was suppressed to values below detection limit and the AA-induced GFR increase was abolished. Continuous intravenous infusion of the DA1 receptor antagonist SCH 23390 (SCH, n = 7) in a dose of 4.0 micrograms/kg/min did not prevent the AA-induced increase in GFR (33 +/- 3%, P < 0.001) and UDA (97 +/- 12%, P < 0.001). In contrast, S-sulpiride (SUL), a specific DA2 receptor antagonist, infused continuously i.v. in a dose of 5 micrograms/kg/min, completely abolished the AA-induced GFR increase, while UDA was increased 1.6 fold (P < 0.01). Like BZD, both dopamine receptor antagonists did not affect renal sodium excretion substantially. Our results suggest, that endogenous dopamine could act as a mediator in the renal response to amino acid infusion in the rat, most likely by activation of DA2 receptors. PMID- 8208303 TI - Presynaptic opioid receptors on dopaminergic nerves in the rabbit caudate nucleus: coupling to pertussis toxin-sensitive G-proteins and interaction with D2 autoreceptors? AB - Slices of the rabbit caudate nucleus, preincubated with [3H]dopamine and subjected to electrical field stimulation, were used (1) to investigate the involvement of G-proteins in the signal transduction of presynaptic D2 (auto)receptors and kappa-opioid receptors on dopaminergic axon terminals in this tissue and (2) to study a possible mutual interaction of these two presynaptic receptors. Pretreatment of the slices with either pertussis toxin (8 micrograms/ml; 18 h), or N-ethylmaleimide (30 microM, 30 min) significantly reduced the inhibitory effects of both the D2 agonist quinpirole and the kappa opioid receptor agonist U-50488H on the [3H]overflow evoked by 36 pulses (2 ms, 24 mA, 0.3 Hz), suggesting the coupling of both receptors to G-proteins. Experiments designed to study possible interactions of these two presynaptic receptors were carried out under stimulation conditions (only 1 pulse), which strongly diminish interference of endogenous transmitters released in the tissue with modulatory effects of exogenous drugs. For instance, due to the presence of endogenous dopamine, quinpirole was much less potent during 36-pulse-than during 1-pulse field stimulation, whereas the D2 antagonist domperidone was almost without effect in the latter case. Using the 1-pulse stimulation paradigm, the concentration/response curve of quinpirole was unaffected in the presence of the half-maximal inhibitory concentration of U-50,488 H (0.1 microM). On the other hand, also quinpirole at its half-maximal inhibitory concentration (0.1 microM), hardly affected the concentration/response curve of U-50,488 H: only high concentrations of U-50,488 H (above 1 microM) seemed to be slightly less effective in the presence than in the absence of the D2 agonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208304 TI - Plasma normetanephrine for examination of extraneuronal uptake and metabolism of noradrenaline in rats. AB - The importance of neuronal reuptake for terminating the actions of noradrenaline is well established, but the role of extraneuronal uptake is less clear. This study used plasma concentrations of the extraneuronal noradrenaline metabolite, normetanephrine, to estimate rates of extraneuronal removal of noradrenaline in rats. Animals received infusions of 3H-noradrenaline, with and without inhibition of catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), to examine the extraneuronal removal of noradrenaline and formation of normetanephrine from infused and endogenous noradrenaline. Infusions of 3H-normetanephrine were also carried out to examine the plasma kinetics of normetanephrine before and after inhibition of MAO. Normetanephrine was cleared rapidly from the circulation and had a short plasma halflife (1 min). Spillover of normetanephrine into plasma (79 pmol kg-1 min-1) was a third that of noradrenaline, but increased 2.8-fold after inhibition of MAO; noradrenaline spillover remained unchanged. Combined inhibition of MAO and COMT decreased the plasma clearance of 3H-noradrenaline by 38%, reflecting removal of 3H-noradrenaline by extraneuronal uptake. Division of the rate of extraneuronal removal of 3H-noradrenaline by the specific activity of plasma 3H-normetanephrine during the 3H-noradrenaline infusion indicated that the rate of extraneuronal removal of endogenous noradrenaline was 250 pmol kg-1 min 1; this was close to the spillover of normetanephrine into plasma after inhibition of MAO (219 pmol kg-1 min-1). Forty-five% of plasma normetanephrine was derived from circulating noradrenaline and 55% from noradrenaline before entry into the circulation. Assuming that these proportions reflected the sources of noradrenaline metabolized extraneuronally indicated that the rate of extraneuronal metabolism of noradrenaline before entry into the circulation was 138 pmol kg-1 min-1. Comparison of this with the rates at which noradrenaline was recaptured by sympathetic nerves (2540 pmol kg-1 min-1) or spilled over into plasma (228 pmol kg-1 min-1), indicated that 87% of the noradrenaline released by sympathetic nerves was recaptured, 5% was metabolized extraneuronally and 8% escaped into plasma. Thus, extraneuronal uptake removes much less of the noradrenaline released by sympathetic nerves than neuronal reuptake. PMID- 8208305 TI - Differential effects of vigabatrin, gamma-acetylenic GABA, aminooxyacetic acid, and valproate on levels of various amino acids in rat brain regions and plasma. AB - Drugs which elevate brain levels of the inhibitory amino acid neurotransmitter GABA by inhibiting the GABA catabolizing enzyme GABA transaminase (GABA-T) have been developed for treatment of brain disease, such as epilepsy. Among all GABA-T inhibitors available, vigabatrin is thought to be the most selective compound, and this drug is the only GABA-T inhibitor in clinical use. However, some previous studies have indicated that vigabatrin might affect the metabolism of several amino acids not directly linked to the GABA shunt. In the present study, various amino acids, involving inhibitory and excitatory neurotransmitters, were determined in 12 brain regions and plasma of rats after treatment with anticonvulsant doses of vigabatrin and the less selective GABA-T inhibitors aminooxyacetic acid (AOAA) and gamma-acetylenic GABA (GAG). Furthermore, the antiepileptic drug valproate, which is also thought to act via the GABA system, was included for comparison. The GABA-T inhibitors markedly enhanced GABA levels in all brain regions examined, while valproate induced only moderate increases in some regions. All drugs, including valproate, significantly decreased aspartate in the brain to a similar extent, and the GABA-T inhibitors but not valproate decreased levels of glutamate. The decreases in aspartate and glutamate levels were not correlated with the different magnitudes of GABA increase produced by GABA-T inhibitors, suggesting that these effects were not simply due to the altered GABA degradation. In addition to glutamate and aspartate, alanine levels were decreased by GABA-T inhibitors but not valproate in several regions. Brain levels of glutamine were decreased by GAG and vigabatrin but increased by valproate and partly also by AOAA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208306 TI - Acute and subchronic benzodiazepine-barbiturate-interactions on behaviour and physiological responses of the mouse. AB - Female NMRI mice were pretreated for 2 weeks with diazepam (D: 20 mg/kg/day), secobarbital (S: 23 mg/kg/day), or combination (D+S: 19 mg/kg/day, each) by means of the drinking fluid. A fourth group remained untreated. One day after this period the mice received an i.p. injection of one out of 16 drug combinations (crossover design: 0, 2, 4, 6 mg/kg D combined with 0, 6, 12, 18 mg/kg S). Open field behaviour, motor performance, and rectal body temperature were measured. In non-pretreated animals, D and S induced immobility, impairment of coordination and hypothermia in a dose-dependent manner. Excitation appeared after low doses of D (2 mg/kg) and high doses of S (12-18 mg/kg). Acute interactions between D and S were studied by means of isobolographic analysis. Dose-additivity indicating a common mechanism of action was confirmed for immobility, impairment of coordination, and hypothermia whereas excitation revealed a non-additive interaction and was reduced after combined administrations. After chronic pretreatment, the mode of acute drug interaction (dose-additive and non-additive, resp.) remained unchanged. Shifts of the isoboles indicated tolerance, cross tolerance or sensitization. There was an asymmetry concerning the pretreatment with D and S. Chronic administration of D induced a tolerance to D in regard to all responses and a sensitization to S-effected motor incordination. Chronic administration of S sensitized the sedative and hypothermic responses to acute D. Metabolic tolerance could not account for the subchronic effects since distinct functional responses were concerned in different ways.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208307 TI - Actions of cisplatin on the electrophysiological properties of cultured dorsal root ganglion neurones from neonatal rats. AB - In this study we have employed the whole cell patch clamp technique to investigate the effects of an anti-cancer drug cisplatin on basic electrophysiological properties of cultured dorsal root ganglion neurones from neonatal rats. The results show that within the clinical concentration range, cisplatin (0.1 to 10 microM) caused a decrease in input conductance, and complex changes in resting membrane potential in these cultured sensory neurones. The dominant effects of cisplatin on input conductance may be due to inhibition of leak conductances. Transplatin (5 microM) was significantly less effective than cisplatin at reducing input conductance which suggests a degree of stereoselectivity. Cisplatin (1 to 5 microM) transiently increased excitability of the cultured neurones as reflected by a reduction in the threshold for activation of action potentials by 8 mV. The rise time, peak amplitude and duration of action potentials were not changed by acute application of 5 microM cisplatin. Long term treatment of neurones with cisplatin (5 microM), for up to 1 week reduced the viability of the cultures, and attenuated neurone excitability, although input conductance of the cells was significantly increased to 322 +/- 49 M omega (n = 9) compared with controls of 210 +/- 20 M omega (n = 30; P < 0.05). Acute and chronic treatment of cultured neurones with cisplatin therefore produced contrasting actions. PMID- 8208308 TI - Comparison of the in vitro binding characteristics of the beta-carbolines harman and norharman in rat brain and liver and in bovine adrenal medulla. AB - The in vitro binding of the naturally occurring beta-carbolines harman and norharman in their tritium-labelled forms to cell membranes from the rat brain and liver and from bovine adrenal medulla was investigated. Displacement of the specific [3H]harman binding in bovine adrenal medulla and rat liver by several beta-carbolines and monoamine oxidase (MAO) inhibitors revealed the pharmacological profile of a single, high-affinity binding site (KD 4.92 +/- 0.43 nmol/l, Bmax 8.47 +/- 0.17 pmol/mg protein; adrenal medulla) which corresponded to the active site of MAO type A (MAO-A). Similar characteristics have previously been found for brain tissue from rat, marmoset and pig. In order to determine the temperature dependence of the [3H]harman binding, the KD and Bmax values for rat cerebral cortex were calculated from the results of saturation experiments at 5 temperatures (range: 0 degree C-37 degrees C). Whereas the Bmax values under all conditions were approximately 4 pmol/mg protein, the KD values, with increasing temperature, ranged from approximately 3 nmol/l to 30 nmol/l. The calculated linear van't Hoff plot (-ln KD against 1/T) suggested an enthalpy-driven binding of [3H]harman to MAO-A. At least three different [3H]norharman-binding sites were detected. In the rat forebrain, approximately 85% of the specific binding (at about 2 nmol/l of [3H]norharman) can be attributed to a MAO binding site of type B: the binding is displaceable, in nmol/l concentrations by the potent and selective MAO-B inhibitors MDL 72,974 A, R(-)-deprenyl and pargyline and, in mumol/l concentrations, by S(+)-deprenyl and the potent and selective MAO-A inhibitors clorgyline, harmine, harman, harmaline, brofaromine 5-F-alpha methyltryptamine. After suppression of the MAO binding sites with 1 mumol/l clorgyline and 1 mumol/l R(-)-deprenyl, a second binding site was found. However, the binding at this site was biphasically displaceable by harman and norharman (Hill-slopes about 0.5 and 0.6, curvilinear Rosenthal plots) suggesting the presence of negative co-operativity or of two binding sites (states). A similar clorgyline/R(-)-deprenyl resistant single (Hill-slopes of displacement by norharman, harman and 6-hydroxy-beta-carboline about unity; linear Rosenthal plots) high affinity binding sites (KD 7.5 +/- 2 nmol/l, Bmax 130+/- 30 fmol/mg protein) was found in bovine adrenal medullary cell membranes. A third quite different clorgyline/R(-)-deprenyl resistant high-affinity (KD approximately 14 nmol/l) and high-density (Bmax 10-30 pmol/mg protein) binding site was detected in the liver.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8208309 TI - Effects of glycyrrhetinic acid on aminonucleoside nephrosis in rats. AB - The effects of glycyrrhetinic acid (GA), an aglycon of glycyrrhizin extracted from the roots of Glycyrrhizae radix, on puromycin aminonucleoside (PA) nephrosis were studied in rats. Urine protein excretion in female rats (130 g-150 g) receiving PA (50 mg/kg) alone was significantly elevated on the 2nd day after injection of PA and reached a peak on the 14th day. Urinary protein on the 14th day was reduced to 74% in animals treated with GA (20 mg/kg) starting on the 2nd day after injection of PA. The increase in serum cholesterol and the decrease in serum protein were also suppressed by GA. Observation by electron microscopy revealed that the degree of abnormality in glomerular epithelial cells, i.e. loss or fusion of foot processes, was lower in the rats treated with GA after PA injection than in the rat treated with PA alone. Moreover, pretreatment with GA did not suppress urinary protein excretion but when it was given at the same time as PA and after PA a significant decrease in urinary protein excretion was observed. PMID- 8208310 TI - Suppressive effect of 2-phenyl-4-quinolone (YT-1) on hind-paw edema and cutaneous vascular plasma extravasation in mice. AB - Like indomethacin, BW755C, diphenhydramine and methysergide, 2-phenyl-4-quinolone (YT-1) suppressed the polymyxin B-induced hind-paw edema. This inhibitory effect of YT-1 was also demonstrated in adrenalectomized mice. YT-1 inhibited the antidromic stimulation of saphenous nerve-induced plasma leakage in dorsal paw skin and reduced the volume of plasma exudation in PCA reaction. Bradykinin-, substance P- and compound 48/80-induced mouse ear edema was suppressed by YT-1 in a dose-dependent manner. In isolated rat peritoneal mast cells, YT-1 produced a dose-dependent inhibition of bradykinin-, substance P- and compound 48/80-induced histamine and beta-glucuronidase release. YT-1 also reduced the TXB2 formation from PMN leukocytes with IC50 2.0 +/- 0.5 microM, however with little effect on LTB4 formation. Histamine- and serotonin-induced plasma exudation in ear edema were reduced by YT-1. Moreover, the maximal response of ileum contraction caused by histamine and serotonin were also suppressed by YT-1 in a dose-dependent manner. In compound 48/80-pretreatment mice, YT-1 failed to suppress the bradykinin- and substance P-induced ear edema to a significantly greater extent than diphenhydramine combined with methysergide did. These results indicate that the inhibitory effect of YT-1 on local edema formation is not through the release of steroid hormones from adrenal gland, and is probably by suppressing the release of chemical mediators from mast cells, inhibition of prostaglandins formation, and noncompetitive but selective protection of the vasculature against the histamine- and serotonin-induced plasma extravasation. PMID- 8208312 TI - To the mechanism of spermine-FBS cytotoxicity toward K562 human myelogenous leukemia cells. AB - The effects of several compounds acting through adenylate cyclase system and/or influencing prostaglandin biosynthesis on spermine-FBS cytotoxicity to human myelogenous leukemia K562 cells were studied. Salbutamol, a beta 2-adrenoceptor agonist inhibited to a certain extent spermine-FBS cytotoxic action to K562 cells, and propranolol, a beta 2-adrenoceptor antagonist, did not affect this inhibition. Aminophylline, an inhibitor of cyclic nucleotide phosphodiesterase, acted suppressing spermine-FBS cytotoxicity to K562 cells. Pretreatment of the cells with dexamethasone did not significantly alter salbutamol-related inhibition of spermine-FBS cytotoxicity. Indomethacin, an inhibitor of cyclooxygenases directly involved in prostaglandin biosynthesis, did not interfere with protective terbutaline effects against spermine-FBS cytotoxicity to K562 cells during the 24-hour period. PMID- 8208311 TI - Levels of circulating peptide and steroid hormones in men with lung cancer. AB - Levels of circulating peptide (FSH, LH, prolactin, ACTH, calcitonin, gastrin and insulin-like growth factor-1 [IGF-1]) and steroid (estradiol, progesterone, DHEA S and testosterone) hormones were estimated by radioimmunoassay (RIA) and immunoradiometric assay (IRMA) in male patients with lung cancer (n = 37) pre therapeutically and compared with 25 age matched healthy controls. In this retrospective study, FSH, LH, prolactin, ACTH, calcitonin, gastrin and IGF-1 were significantly higher with concomitant lower levels of DHEA-S and testosterone, while the difference was statistically non-significant for estradiol and progesterone in patients with lung cancer when compared with controls. Early stage patients (Stage II) exhibited higher levels of gastrin as compared to advanced stage patients (Stages III and IV). It is suggested that hormonal imbalance might play an important role in the development and progression in male patients with lung cancer. PMID- 8208313 TI - Adhesiveness of granulocyte precursors in chronic granulocytic leukemia. AB - Adhesiveness of myeloblasts, promyelocytes, myelocytes, metamyelocytes, bands and polymorphonuclear neutrophils (PMN's) from the blood of patients with chronic granulocytic leukemia (CGL) was studied. The adhesiveness of the cells to the substrate (glass) was tested in the presence of protein under dynamic conditions, i.e. when the suspension of cells was flowing over the substrate. It was found that adhesiveness of the CGL granulocyte precursors increased with maturation except for the myeloblasts. They exhibited a greater adhesiveness than the more mature promyelocytes. Changes in the physical and chemical parameters of CGL granulocytes occurring during maturation are discusses in the aspect of their adhesiveness. PMID- 8208314 TI - Early diagnosis of breast cancer dissemination by tumor markers follow-up and method of prediction. AB - A mathematical model of prediction of progression was tested in patients with breast cancer employing long-term monitoring of tumor markers CEA, CA 15-3, MCA and TPA, erythrocyte sedimentation rate (FW), and the enzymes gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and lactate dehydrogenase (LD) in serum. At the same time, specificity, sensitivity, lead time and positive predictive value were evaluated along with false positivity for all these parameters and their combinations. A model was proposed for the follow-up of patients with breast cancer after the completion of basic therapy. PMID- 8208315 TI - Location of primary and recurrent superficial bladder tumors and benefits of selective biopsies. AB - Surgical records and bladder diagrams of 856 patients suffering from superficial bladder cancer were summarized into bladder tumor maps. Areas of high tumor density were created giving thus an opportunity to take selective cold cup biopsies. Two hundred and sixteen tissue samples were taken in a group of 62 patients and 12.1% positive results were obtained. The benefit of routinely performed selective biopsies during the first surgery have been discussed. PMID- 8208316 TI - Tumor cytotoxicity and production of interleukin-1 and tumor necrosis factor from blood monocytes of cervical carcinoma patients. AB - To assess the functional integrity of monocytes in patients with cervical carcinoma, cytotoxic potential of peripheral blood monocytes and their ability to secrete interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) after activation with different stimulating agents were studied. Comparable levels of monocyte-mediated cytotoxicity were observed in healthy donors and patients. The production of IL-1 and TNF-alpha by monocytes of healthy donors and patients was similar indicating no defect in monocyte functions in these patients. PMID- 8208317 TI - Cytoplasmic and surface membrane phenotypic markers in cells of B cell chronic lymphocytic leukemia. AB - Peripheral blood cells of twenty-six patients with B cell chronic lymphocytic leukemia (B-CLL) were characterized for their surface membrane and cytoplasmic marker profiles using flow cytometry and fluorescence microscopy. According to surface membrane marker analysis three distinct immunophenotypic subgroups of B CLL were identified: group I (SIg+, MR+, CD5+, B Ag+, T Ag-; 19 cases), group II (SIg+, MR+, CD5+, B Ag+, TAg+; 3 cases), group III (SIg-, MR+, CD5+, B Ag+, T Ag ; 4 cases). Cells from all patients were positive for the CD19 antigen and at least one of other B cell antigens. Cells from all patients expressed also CD5 and HLA-DR antigens and formed mouse rosettes (MR). Great heterogeneity was found in the membrane and cytoplasmic marking by anti-CD22 MoAb. In four of 23 patients tested, CD22 antigen was expressed in the cytoplasm of CLL cells while it was absent on surface membrane of these cells. This finding was discussed from the point of certain cell heterogeneity in the followed B-CLL cases. Cytoplasmic immunoglobulin (CyIg) detection showed to be very important especially in group III of followed B-CLL cases with undetectable surface immunoglobulins (SIg). Cytoplasmic antigens and immunoglobulin determinations are useful in phenotyping every B-CLL patient, as well as in the immunological study of different maturation stages of B lymphocytes. PMID- 8208318 TI - Augmentation of NK cell activity and proliferation in cultured lymphocytes of leukemic patients by monoclonal antibodies CD3 and interleukin-2. AB - The aim of the present study was to induce NK cell activity in peripheral mononuclear cells (PMNC) of normal individuals or of leukemic patients. For this purpose, monoclonal antibodies (mAbs) anti-CD3 (MEM 57, OKT 3 and MEM 92), anti CD59 (MEM 43) and anti-CD43 (MEM 59) were tested. MEM 43, MEM 59, MEM 57 and OKT 3 stimulated markedly the NK activity in fresh isolated PMNC of normal individuals, whereas the cytotoxicity in 3-day cultivated PMNC was enhanced only by MEM 57 and OKT 3. In comparison to interleukin-2 (IL-2), MEM 57 and OKT 3 induced less PMNC cytotoxicity but more cell proliferation. MEM 92 (anti-CD3, IgM) compared to MEM 57 or OKT 3 (anti-CD3, IgG) did not show any effect on both reactions mentioned above. PMNC of untreated leukemic patients exerted very negligible NK cell activity. Following 3-day culture of leukemic PMNC with OKT 3 or IL-2 the anti-K 562 cytotoxicity was markedly enhanced. In some cases the stimulating effect was more pronounced by IL-2, in others by OKT 3. Nevertheless, the best effect was gained in 7 out of 12 patients using a combination of IL-2 and OKT 3. On the other hand, OKT 3 did not synergize with IL-2 in normal PMNC culture. PMID- 8208319 TI - Aging and radiation induced alterations in liver histones. AB - Age-related changes in histones in the liver of normal rats and in rats irradiated with 5.7 Gy gamma rays were examined. Quantitative histone changes in growing and aging rats (from 1 to 28 months of age) were found to be mild only. As they paralleled the DNA changes, the histone/DNA ratio remained stable with age. In total extracted histones there was a decrease in the H1 proportion in older age groups with preceding increase in the H10 proportion. Thirty minutes after irradiation the amount of histones was reduced with age, probably due to an impaired extractability of histones. As the quantitative DNA changes were milder, the histone/DNA ratio decreased in aging liver after irradiation. Similar patterns of changes in proportion of the H1 fraction and H10 subfraction were observed in irradiated and nonirradiated animals, in the former with an earlier onset. Irradiation, therefore, accelerated spontaneous age-related alterations. PMID- 8208320 TI - Papillomavirus genomes in human cervical carcinoma: analysis of their integration and transcriptional activity. AB - Eighty-four biopsies derived from cervical tissues were analyzed for the presence of human papillomavirus (HPV) DNA types 6, 16 and 18 using Southern blot hybridization. HPV 6 was found in none of the cervical biopsies, and HPV types 16 and 18 were found in 44% of them. The rate of HPV 16/18 positive samples increased proportionally to the severity of the lesion. In normal tissue there were no positive samples, in mild and moderate dysplasias HPV 16/18 was present in 20% and in severe dysplasias and invasive carcinomas in 37 and 50%, respectively. In biopsies from 13 cases with squamous cell carcinoma of the uterine cervix and CIN III lesions HPV 16 was integrated within the host genome. It was concluded that the virus could be integrated at variable, presumably randomly selected chromosomal loci and with different number of copies. Transcription of HPV 16 and 18 was detected in one cervical cancer and in HeLa cells, respectively. These results imply that HPV types 16 and 18 play an etiological role in the carcinogenesis of human cervical epithelial cells. PMID- 8208321 TI - Dutch Society of Gastroenterology and Dutch Society of Hepatology meeting. Veldhoven, 7-8 October 1993. Abstracts. PMID- 8208322 TI - Adjuvant treatment of colon cancer. A plea for a large-scale European trial. PMID- 8208323 TI - Comparison of clinical examination, current and vibratory perception threshold in diabetic polyneuropathy. AB - The study of diabetic polyneuropathy is complicated by a lack of clear definitions and the absence of a simple reliable test procedure. Recently, a new sensory perception testing device has been introduced for detection of thresholds for electrical stimuli (current perception: CPT) at different frequencies (Neurometer). We compared standardized clinical examination scores with measurements of vibratory perception threshold (VPT) and CPT (foot) and obtained reproducibility figures. Participants in the study were healthy controls (H, n = 33), diabetic patients without clinical signs of neuropathy (DN-, n = 23), diabetics with overt diabetic neuropathy (DN+, n = 22), and patients with a diabetes duration of over 20 years (D20, n = 38). As expected, there were highly significant differences (Wilcoxon) in CPT, VPT and neurological scores between H/DN- and DN+ (p < 0.001), but not between H and DN-. Correlation between CPT and total as well as partial (reflecting small and large fibre functions) neurological examination score were highest at 2000 Hz (r = 0.88); no advantage of lower frequency CPT could be identified. CPT seemed rather insensitive in detecting neuropathy. Correlations between CPT and VPT were only moderate and maximal at 2000 Hz (r = 0.61). Reproducibility of CPT was good at 2000 Hz (coefficient of variation 13.3-20.2%), but moderate to poor at lower frequencies (ranging to 62%). We conclude that CPT and VPT quantitative sensory testing is only of limited value, mainly because of high variability and poor reproducibility. PMID- 8208324 TI - Diagnosis of clinically suspected pulmonary embolism: a survey of current practice in a teaching hospital. AB - OBJECTIVE: To assess the diagnostic and therapeutic management of patients with clinically suspected pulmonary embolism. METHODS: A prospective survey of the management of patients with clinically suspected pulmonary embolism was carried out in two teaching hospitals in Amsterdam, without the knowledge of the attending physicians. Use and timing of lung scintigraphy and other tests for venous thromboembolism, therapeutic consequences and duration of hospitalization were evaluated. RESULTS: Of 89 outpatients and 116 inpatients, 97% of patients underwent lung scintigraphy. Lung scan results were normal in 51% of outpatients and 20% of directly admitted patients; high probability in 10% and 22% and non diagnostic in 39% and 58%, respectively. Twenty-two outpatients were subsequently admitted (1 normal, 9 high-probability and 12 non-high-probability lung scans). Pulmonary angiography and tests for deep vein thrombosis were performed in 7 (10%) and 21 (29%) of admitted patients with a non-diagnostic lung scan outcome, respectively. Of 138 admitted patients, 75 (54%) received heparin for 5 or more days. All patients with high-probability lung scans and none with a normal lung scan received long-term anticoagulants. Of patients with non-diagnostic lung scans, therapeutic decisions were mainly based on clinical grounds, and 44% were prescribed oral anticoagulants. The median duration of hospitalization was 6 days, 14 days and 13 days for patients with a normal lung scan, a non-diagnostic lung scan and a high-probability lung scan outcome, respectively. CONCLUSION: Diagnostic delay in directly hospitalized patients results in anticoagulation of patients without pulmonary embolism and excessive hospitalization. Guidelines for the diagnostic management of patients with non-diagnostic lung scans are urgently required. PMID- 8208325 TI - Q-fever in a patient with a ventriculo-peritoneal drain. Case report and short review of the literature. AB - Although Q-fever is still a relatively rare disease in the Netherlands, its incidence seems to be increasing. In this article we describe the case-history of a 65-year-old woman with a Pudenz-drain, who acquired Q-fever pneumonia while manuring her garden. The course of the disease was deviant, which most likely was caused by colonization of the ventriculo-peritoneal drain with Coxiella burnetii. Q-fever usually presents as a self-limiting illness. In the case of chronic Q fever, complications such as endocarditis, hepatitis or meningo-encephalitis can be fatal and require long-term treatment. Patients with artificial drains or valves carry a greater risk of developing such complications. Therefore, especially in patients at risk, Q-fever should be included in the differential diagnosis when dealing with a patient with unexplained fever. PMID- 8208326 TI - Biochemical markers of bone turnover: an update. AB - Currently, biomarkers are available which have considerably increased the possibility of monitoring changes in bone turnover. Assays for carboxy-terminal procollagen I fragments, osteocalcin and the bone-specific isoenzyme of alkaline phosphatase allow a more precise assessment of the complex osteoblastic functions in health and disease; osteocalcin appears at present to be the most satisfactory one. With respect to bone resorption, the measurement of urinary pyridinoline cross-links seems to be the most reliable assay. It has to be emphasized, however, that a single biomarker may be of value in some metabolic bone diseases but not in others. PMID- 8208327 TI - [Natural history and spontaneous prognosis of cerebral arteriovenous malformations]. AB - Eight large series of patients presenting with untreated cerebral arterio-venous malformations (A.V.M.) were reviewed. Data were gathered on 1134 patients who were followed for 20 years or more. The risk of rupture and the rate of other complications were estimated, in relation with other factors like age of patient, size of A.V.M., or hemodynamic stresses. The prevalence of A.V.M. at autopsy is 14 per 10,000 population. Fifty percent of A.V.M.s remain asymptomatic during the whole patient's life. The risk of hemorrhage from rupture of an A.V.M. is 2% per year and per patient. Hemorrhage is more frequent from small-sized A.V.M.s, mostly under certain hemodynamic factors. The risk of hemorrhage is also higher in children between 5 and 10 years of age, and in women to the end of pregnancy. The incidence of seizures and neurological impairment is approximately 1% per year and per patient, and these symptoms mostly occur in elder patients with large A.V.M.s. If the A.V.M. has not been revealed by hemorrhage, the risk of rupture is 1% per year and per patient. The incidence of complications from fortuitously diagnosed A.V.M.s seems very low, and even nil in some series. The risks of therapeutic procedures could not be determined, but in some A.V.M.s, the association of different therapeutic means seems mor advisable than isolated therapy. The analysis of natural history of A.V.M.s is desirable to provide a better information to the patient, and to define the limits of therapeutic indications. PMID- 8208328 TI - [The neurosurgeon's role in the treatment of cerebral arteriovenous malformations. A study of a series of 100 cases and review of the literature]. AB - The Neurosurgeons's place in the management of cerebral A.V.M.'s is discussed in the light of a personal experience and of the review of the neurosurgical literature. A personal series of 100 treated patients is presented. Patients were admitted between 1985 and April 1992. Two groups are considered: the first group including 52 patients treated before the availability of radiosurgery (1985 1988), and the second group including 48 patients treated afterwards (1989-1992). A.V.M.'s were classified in five grades according to the Spetlzer's Grading System. Three techniques of treatment were used: Surgical Resection, Intravascular Embolization (cyanoacrylate) and Radiosurgery (linear accelerator). These three techniques were used either alone or in association, giving four types of management: surgical resection alone, embolization and resection, embolization alone, and radiosurgery (alone, or after embolization or after surgical resection). From 1989 on, the availability of radiosurgery was responsible for the diminution of the "embolization and resection" group, which until then was predominantly used, for the low-grade A.V.M.'s (I.II.III) and for the high grade A.V.M.'s (IV.V) as well. Overall, for the low grade A.V.M.'s, the treatment of choice was the surgical resection (79% of cases), with a preoperative embolization in one half of these cases; the other A.V.M.'s were irradiated, with various combinations. For the high-grade A.V.M.'s, the treatment of choice was the intravascular embolization (95% of cases), either alone, or followed by exeresis (45%) or radiosurgery (9%). Results were evaluated in terms of deterioration due to treatment, in five groups: no deterioration (59%), minor deterioration (20%), long-lasting deficit (10%), major deterioration (5%) and death (6%). Overall, results improved after 1989: favourable outcome (no deterioration and minor deterioration) increased from 67% to 90%. Results were not related to the patient's age. More favourable results were obtained for low grade A.V.M.'s (93%) than for high grade A.V.M.'s (60%). For the low grade A.V.M.S. the evolution form 1989 on (favourable outcome increasing from 89% to 96%) occurred with the suppression of death cases. For the high grade A.V.M.'s, the evolution from 1989 on (favourable outcome increasing from 46% to 78%), occurred with the decreasing of the deficit cases. The angiographic eradication was strongly related to the management: 95% of complete eradication after surgical resection and 5% only after embolization alone. Concerning the results in irradiated cases, the follow-up is not long enough. The review of the neurosurgical literature since 1972 demonstrates progressive modifications in the therapeutic attitude as regards A.V.M.'s. The surgical management which was predominantly used at the beginning gave progressively way to a combined management, with a combination of embolization, surgery, and lately radiosurgery.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8208330 TI - [Nucleotomy of the spinal trigeminal nucleus. Apropos of 2 post-traumatic neuralgia with surgical treatment]. AB - This report describes two patients with medically intractable post-traumatique trigeminal neuralgia, who underwent bipolar coagulation of the pars caudalis of the trigeminal spinal nucleus. Follow-up examination--36 months and 7 months, respectively, after the procedure-showed that the patients were free of pain. PMID- 8208329 TI - [Familial aneurysms, multiple aneurysms and "de novo" aneurysms. Apropos of 2 cases]. AB - The authors report the case of two sisters: each suffered from two intracranial hemorrhages caused by aneurysmal rupture at an interval of respectively 8 and 5 years. In the first case, the first subarachnoid hemorrhage (SAH) was related to a left middle cerebral artery aneurysm and the second, 8 years later, to the rupture of one of three right aneurysms (anterior communicating, supraclinoid internal carotid and middle cerebral arteries). But the "de novo" character of the right aneurysms could not be established. In the second case, the first SAH was related to an aneurysm of the right middle cerebral artery, with the left one appearing normal on the initial angiography. The second SAH, 5 years later, was related to a "de novo" left aneurysm. These two observations of familial, multiple and "de novo" intracranial aneurysms suggest a genetic basis for the pathogenesis of the arterial dysplasia. As in the literature, these hypothetical congenital factors could not be identified in both cases, but their probability justifies further investigations. If this factor exists, can we hope for a total recovery of the aneurysmal disease? PMID- 8208331 TI - [Sphenoido-nasopharyngeal craniopharyngioma. A case with radical excision by Le Fort I-type maxillotomy]. AB - A case of infra-sellar (sphenoidal nasopharyngeal) craniopharyngioma is reported. A 16 year-old girl presented with progressive nasal obstruction. CT and MR images showed a heterogeneous tumor originating from the sphenoid bone with no intra cranial or supra-sellar extension. On a biopsy specimen, the histologic examination was consistent with a craniopharyngioma. The tumor was successfully removed via an inferior route using a Le Fort I maxillotomy. Plates and screws were used to achieve osteosynthesis. The post-operative course was uneventful and there was no residual tumor on post-operative CT. Craniopharyngiomas with strictly infra-sellar development are very rare. Up to now, 19 cases have been reported in the literature. This condition likely results from growth of embryonic remnants lying along the craniopharyngeal duct. Several surgical approaches have been proposed, most of those giving poor exposure to the clival and lateral tumorous extensions. Of particular interest in the authors' experience was the use of a Le Fort I maxillotomy which provided optimal exposure to the skull-base and facilitated radical excision. CT and MR studies have proved of upmost importance in delineating the area of bone to be removed at operation. PMID- 8208332 TI - [Epidermoid cyst of the 4th ventricle. Apropos of a case in a child and review of the literature]. AB - A 6 year-old child was admitted for a recurrent bacterial meningitis at Proteus Morganii. She was treated with antibiotics. The C.T. Scanner showed a midline low density lesion, with a mild annular contrast uptake in the posterior fossa. M.R.I. showed the lesion and revealed a skin-bone-dura fistula. The surgical resection was complete. It was an epidermoid tumor. Intracranial epidermoid tumors constitute about 1% of brain tumors and are considered to be congenital. Epidermoid tumors of the 4th ventricle are exceedingly rare in childhood. The authors reviewed the literature and discuss the pathogeny, the radiographic diagnosis and the treatment of these tumors. PMID- 8208333 TI - [Tuberculous spondylodiscitis. Diagnostic elements and value of MRI. Apropos of a cervical localization]. AB - The authors report a case of tuberculous spondylodiscitis with an intracanalar ant retropharyngeal involvement. This pathology is recently increasing like the immunodeficiency syndromes. Cervical tissue compression and neurological signs are the main clinical findings. Among the radiological explorations of disco vertebral infections, the value of MRI study is now admitted. Using of T1 and T2 weighted sequences and Gadolinium injection provides the positive diagnosis, and well visualizes the extent: low signal of vertebral body, decrease and low signal of discal space, prevertebral and retrovertebral enlargement with a low signal intensity of the abscess in T1 weighted sequence and enhancement following Gd DTPA administration; high signal intensity of vertebral body, prevertebral and epidural masses and abscess in T2 weighted sequence. The authors describe the evolutive features of Pott's disease and the value of MRI in the post-therapeutic course: T1-signal increases while enhancement following Gd-DTPA administration decreases and T2-signal decreases. The differential diagnosis with chordomas, metastasis, and pyogenic spondylodiscitis is well assessed by MRI. PMID- 8208334 TI - [Surgical treatment of stenosis-thrombosis of internal carotids by extra intracranial arterial anastomosis and endarterectomy]. AB - The surgery of the remaining carotid artery is a very difficult procedure considering the high risk related to the peroperative clamping. Extracranial to intracranial by pass of the thrombosed side permit to carry out in better conditions the contralateral endarterectomy without using intravascular shunt. PMID- 8208335 TI - [Transmission of neurosurgical medical records through computers. Simple reality, considerable progress]. AB - Tests on the transmission of view data processing images were undertaken for 5 months from two experimental micro-processing sites specialized in medical imagery and linked to the R.N.I.S. network. The aim of the research was to validate the equipment and the software, and to find a way of working with regard problems related to long-distance diagnosis. Using an everyday equipment like Apple Macintosh II fx, 75 files were transferred corresponding in 375 images (1% conventional X-ray, 5% digital angiography, 31% scanner and 63% M.R.I.). It has been found that the transfer of medical data is reliable (the images do not deteriorate), easy (less than 3 hours to be familiar with the program) and above all fast (actual transfer time: 8.72 Ko per second). Neurosurgeon and neuroradiologist writers talk about their experience in this field. PMID- 8208336 TI - Hirano bodies and chronic alcoholism. AB - Experiments on rodents have shown convincingly that chronic ethanol ingestion may damage the hippocampal formation. Nevertheless this region has, hitherto, not been considered as a target for alcoholism-induced brain lesions in man. Guided by the observation of increased numbers of Hirano bodies (HB) in the hippocampus of chronic alcoholics, this study determines the maximum number of HB per high power field (HPF: 0.19 mm2) in the stratum pyramidale (HBpyr) and in the stratum lacunosum (HBlac) of Ammon's horn in 123 chronic alcoholics and in 197 controls. The average count of HBlac found in alcoholics was 14.4 (SD = 17.7) compared with 4.2 (SD = 7.4) in non-alcoholics (P < 0.001). Counts of more than 19 HBlac per HPF were revealed as highly indicative of chronic alcoholism being observed in 33 (27%) alcoholics and in six (3%) non-alcoholics (P < 0.001). An increased number of HBlac was the most frequent of the neuropathological findings in the alcoholics. Affirming observations of others, the count of HBlac peaked during middle age and declined thereafter. The maximum count of HBpyr, in contrast, increased with age and was independent of alcoholism. It is proposed that increased numbers of HBlac indicate alterations of the apical dendrites of the pyramidal neurons of the CA1 field of Ammon's horn which probably are due to direct neurotoxic effects of ethanol and which may be reversible in nature. PMID- 8208337 TI - Autosomal dominant arteriopathic leuko-encephalopathy and Alzheimer's disease. AB - A 49-year-old man suffered from progressive dementia and seizures leading to death after 2 years. CT scans showed severe cortical-subcortical atrophy and hypodensity of the white matter. His father had died at about the same age with similar clinical signs. Two sisters and one brother were also affected. Neuropathological study revealed predominant involvement of the cerebral white matter with myelin loss, gliosis and type I lacunes. The small arteries and arterioles of the white matter and basal ganglia, and, to a lesser extent those of the subarachnoidal space, displayed fibrosis and replacement of the media by an eosinophilic, PAS positive, Congo Red negative, granular substance. Electron microscopy showed swollen myocytes surrounded by collagen, elastin and a compact electron-dense material. Immunofluorescence using antibodies against IgA, IgG, IgM, C1q and C3 stained the abnormal media weakly. In the cortex, there were diffuse senile plaques and neurofibrillary tangles. Immunohistochemistry demonstrated beta/A4 positive material in cortical senile plaques but not in arterial walls. Adventitial macrophages were, however, immunoreactive for gamma trace. Systemic arterioles were normal. The vascular changes and leukoencephalopathy are comparable to those described in 'Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy' (CADASIL). Similar vascular changes were also observed in nonfamilial cases. An association with Alzheimer changes in the cortex has not been described previously. The relationship between both diseases and the role of each in the causation of the dementia is unclear. PMID- 8208338 TI - Hirano bodies and related neuronal inclusions. AB - Hirano bodies are bright eosinophilic intracytoplasmic inclusions which have a highly characteristic crystalloid fine structure. They occur preferentially in the neuronal processes of the CA1 area in Ammon's horn in a wide variety of conditions, especially amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam, Alzheimer's disease, Pick's disease and 'normal' elderly individuals. Hirano bodies contain epitopes of actin, actin-associated proteins, tau, middle molecular weight neurofilaments subunit and a C-terminal fragment of beta-amyloid precursor protein. In addition to the CA1 area of Ammon's horn, they have also been identified in many other areas of the nervous system in humans and various experimental animals. Although usually observed in neurons, Hirano bodies may also be present in other cell types. It is the consensus that Hirano bodies in the pyramidal layer of CA1 originate largely from an age-related alteration of the microfilamentous system. PMID- 8208339 TI - Partial reversal of aluminium-induced neurofibrillary degeneration by desferrioxamine in adult male rabbits. AB - Desferrioxamine, a chelating agent with a high affinity for aluminium, has been reported to slow the clinical progression of dementia associated with Alzheimer's disease [4]. We report here the effects of desferrioxamine treatment on aluminium induced neurofibrillary degeneration in rabbits. Adult male New Zealand white rabbits received a single injection of aluminium-maltolate into the lateral cerebral ventricle. Three days later, one group of rabbits was treated with intramuscular injections of desferrioxamine twice daily; a second group received saline instead of desferrioxamine. Both groups were sacrificed 4 or 5 days following initiation of desferrioxamine or saline treatment. Minimal neurofibrillary degeneration was found in two of six desferrioxamine-treated rabbits, while all six rabbits treated with saline showed extensive neurofibrillary degeneration, particularly in the ventral horn of the lower spinal cord. Quantitation of the neurofibrillary degeneration in ventral horn neurons of lumbar cord revealed 30% to be affected in saline-treated animals compared to zero-affected neurons following desferrioxamine treatment. When sacrificed just 3 days after aluminium treatment, 50% of the rabbits already revealed neurofibrillary degeneration, corresponding to the time-point when desferrioxamine treatment was begun in the above animals; on quantitation, 7.5% of ventral lumbar cord neurons were involved. These findings indicate a partial reversal of aluminium-induced neurodegeneration by desferrioxamine. Delaying desferrioxamine treatment to 6 days after aluminium administration prevented any reversal of the aluminium effect; all animals had abundant neurofibrillary degeneration as well as a striking basophilic spicular deposit of calcium and argyrophilic material in the leptomeninges, lateral ventricles and brain parenchyma adjacent to these areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208340 TI - Characterization of the microglial response in murine scrapie. AB - The nature of the glial and inflammatory cell responses to infection in scrapie affected brains was studied in terminally-affected mice of five scrapie models. There were marked astrocytic and microglial responses. Microglia showed increased staining of the surface antigens F4/80, leucocyte-common antigen, type 3 complement receptor, and elevated endocytotic and lysosomal activity. In all models, the astrocytic and microglial responses were largely restricted to anatomical regions of the brain showing vacuolation and/or plaque formation and pathological accumulations of PrP. Expression of MHC Class II was patchy and present on microglia in the neuropil of areas with the most intense microglial activation and on occasional perivascular macrophages. This microglial response may represent a modified form of inflammatory response. PMID- 8208341 TI - Oedema-related tissue damage after temporary and permanent occlusion of the middle cerebral artery. AB - Eleven adults spontaneously-hypertensive male rats (SHR) were studied 22 h or 7 days after a 2 h unilateral occlusion of the right middle cerebral artery (MCA). Another 11 SHR were studied after 24 h or 7 days of permanent MCA ligation. The brain infarcts were significantly larger (P < 0.05) after permanent occlusion than after a 2 h occlusion. More extensive and widespread vasogenic oedema, emanating from the infarcts, was visualized immunohistochemically in the temporarily-ligated animals and the relative number of astrocytes in their contralateral hemispheres was greater, thereby indicating that the vasogenic oedema influences the degree of gliosis. An immunopositivity for albumin but not for fibrinogen extended via the white matter into the ipsilateral thalamic nuclei, where cytolytic nerve cell damage, severely shrunken and karyorrhectic nerve cells as well as gliosis were found one week after permanent and temporary MCA ligation. The histological changes in the thalamus indicated a difference in timing between lateral and medial parts of the lesion as well as between temporarily- and permanently-ligated SHR. These findings together with the close spatial correlation with albumin immunoreactivity indicate that the spread of extravasated plasma constituents or degradation products with the oedema bulk flow from the infarct influences the timing, character and extent of thalamic lesions after cerebral infarction. PMID- 8208342 TI - New immunocytochemical evidence for a neuronal/oligodendroglial origin for corpora amylacea. AB - Studies employing a bank of antisera applied to sections of LR White embedded AD and normal ageing brain tissue, may throw new light on the derivation of CA. Conspicuous levels of immunoreactivity were found in the CA of both tissues with markers for oligodendrocytic proteins such as antisera against myelin basic proteolipid protein, galactocerebroside and myelin/oligodendrocyte glycoprotein. CA were unreactive with MRC OX-42, a marker for microglia and macrophages. In a previous publication we demonstrated that the much more abundant CA in the brains of Alzheimer's disease (AD) sufferers, although slightly more varied in their immunoreactivity than those found in normally ageing controls, were universally immunoreactive with anti-tau, a neuronally derived protein and often also contained amyloid. The cores of CA were not immunoreactive with anti-GFAP, suggesting a lack of involvement with astrocytes. Our results now show that in addition to amyloid and neuronal proteins, a significant proportion of the content of CA is derived from oligodendrocytes and/or myelin. The substantial Fe peak previously reported following X-ray microanalysis of CA was probably due to ferritin. However, immunostaining with antisera to ferritin showed that high ferritin immunoreactivity was common to both micro- and macroglia as well as CA. More significantly, the immunoreactivity of CA with anti-ubiquitin suggests that degeneration of neuronal/oligodendrocytic elements may precede CA formation. PMID- 8208343 TI - Microsatellite analysis of loss of heterozygosity on chromosomes 9q, 11p and 17p in medulloblastomas. AB - Medulloblastoma (MB) is a primitive neuroectodermal tumour of the cerebellum whose pathogenesis is poorly understood. Previous studies suggest a role for loci on chromosomes 11p and 17p in the pathogenesis of MB. Evidence for another potential MB locus has recently emerged from studies on Gorlin syndrome (GS), an autosomal dominant syndrome with multiple basal cell carcinomas, epithelial jaw cysts, and skeletal anomalies. Since GS can be associated with MB, we examined sporadic (non-GS) cases of MB for evidence of loss of heterozygosity (LOH) on chromosome 9 where a putative GS locus has been localized to band q31. Nineteen paired blood and MB DNA specimens from 16 patients (11 primary tumours, two primary with recurrent tumours, one primary tumour and cell line, two cell lines) were studied by PCR analysis of microsatellites at D9S55 (9p12), D9S15 (9q13 q21.1), D9S127 (9q21.1-21.3), D9S12 (9q22.3), D9S58 (9q22.3-q31), D9S109 (9q31), D9S53 (9q31), GSN (9q33), D9S60 (9q33-q34), D9S65 (9q33-q34), ASS (9q34), D9S67 (9q34.3), TH (11p15.5), D11S490 (11q23.3), D17S261 (17p11.2-12), D17S520 (17p12), TP53 (17p13.1), D17S5 (17p13.3), D17S515 (17q22-qter), and by RFLP analysis at the WT-1 locus (11p13). Only two tumours had LOH on 9q. One was non-informative at D9S15, D9S65, and GSN but showed LOH at D9S127, D9S12, D9S58, D9S109, D9S53, D9S60, ASS, and D9S67. The other was uninterpretable at D9S65 and non-informative at D9S15, D9S58, D9S53, and D9S67 but exhibited LOH at D9S127, D9S12, D9S109, GSN, D9S60, and ASS. Both these cases were informative at D9S55 without LOH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208344 TI - Blood-Brain Barrier Workshop, Portrush, County Antrim, Northern Ireland, 2 October 1993. PMID- 8208345 TI - Neurological complications in children with protein C deficiency. AB - Four children with a cerebrovascular occlusive accident and protein C deficiency are described. Two patients presented with an acute hemiplegia, the others suffered from a transient ischemic attack and a progressive hydrocephalus as the result of sinus thrombosis. In all cases protein C deficiency, Type 1, was diagnosed. Other causes of cerebrovascular disease were excluded. Although venous thrombosis has been extensively reported in protein C deficiency, these cases indicate that protein C deficiency is also related to arterial thrombosis. In evaluating children with cerebrovascular accidents, protein C deficiency should also be considered. PMID- 8208346 TI - Linkage analysis of idiopathic generalised epilepsy in families of probands with Juvenile Myoclonic Epilepsy and marker loci in the region of EPM 1 on chromosome 21 q: Unverricht-Lundborg disease and JME are not allelic variants. AB - The locus for Unverricht-Lundborg disease, EPM 1, has recently been mapped to chromosome 21q22.3. A locus, EJM 1, predisposing to idiopathic generalised epilepsy in families of probands with juvenile myoclonic epilepsy has been localised to chromosome 6p by evidence of linkage to the HLA region. However, segregation analysis suggests a two-locus model for JME and evidence has been obtained for genetic heterogeneity within the JME/IGE phenotype. EPM 1 was therefore investigated as a candidate locus in the set of families segregating for IGE and JME which do not show linkage to markers on chromosome 6p. Linkage analysis was carried out in 25 families using three microsatellite DNA markers around the EPM 1 gene region using different models of inheritance. Multipoint linkage analysis provided definite exclusion for 20cM around PFKL, the closet linked marker to EPM 1, under three out of four models tested. These results strongly suggest that the EPM 1 gene is not linked to the phenotype expressed in these families, and therefore that Unverricht-Lundborg disease and juvenile myoclonic epilepsy are not allelic variants. PMID- 8208347 TI - Intracranial germ cell tumors: a comprehensive update of the European data. AB - Intracranial germ cell tumors are rare tumor entities in childhood and adolescents. Extra- and intracranial germ cell tumors are identical in their histologic pattern and occur in preferential midline localizations such as the pineal and the suprasellar region. Germ cell neoplasms show increasing incidence rates over the last 30 years. The majority of intracranial germ cell neoplasms are germinomas. About 90% of the patients with pure germinomas can be salvaged by radiotherapy alone according to modern protocols. Non-germinomatous malignant CNS germ cell tumors are considered to have a poor prognosis. In order to improve the survival of patients affected by these tumors different treatment approaches adding chemotherapy to conventional surgery and radiotherapy have been initiated by various study groups throughout the world. Due to the rarity of these neoplasms only a very limited number of patients has been enrolled in each study. In 1993 an international working group on these tumors was established by the International Society of Pediatric Oncology (SIOP). PMID- 8208348 TI - Disordered peripheral nerve conduction in DOOR(S) syndrome. AB - A case of DOOR(S) syndrome is detailed and the neurophysiological abnormalities observed in this patient and in other cases with this rare but recognisable autosomal recessive condition are considered. Particular emphasis is paid to the abnormal peripheral nerve conduction, which has not previously been recorded in the condition. PMID- 8208349 TI - Etoposide treatment in recurrent medulloblastoma. AB - Five consecutive patients with recurrent medulloblastoma received etoposide 120 mg/m2 for 5 to 7 days at 2 to 4-week intervals. Three patients with neuroaxis dissemination received additional intrathecal chemotherapy with methotrexate, cytosine arabinoside and prednisone. Toxicity consisted of alopecia and mild neutropenia. Complete response was registered in two patients, partial response in one. Median survival was 19 months with the 3 responders living 6, 30 and 60+ months. Etoposide seems to be an active agent in medulloblastoma. PMID- 8208350 TI - Inherited or acquired disorders of blood coagulation in children with neurovascular complications. AB - Congenital or acquired disorders of hemostasis can cause thrombotic events in adults as well as in children. Recently, acute neurologic complications such as hemiparesis or transitory ischemic attacks (TIA) have been reported in patients with different disorders of hemostasis. In addition, the interaction between anionic antiphospholipid antibodies and inhibition of the coagulation have to be considered for these clinical manifestation. This review aims at putting the clinical and experimental data which are currently available for children into perspective. PMID- 8208351 TI - Bilateral arachnoid cysts, seizures and severe encephalopathy: case report. AB - A case is presented of a 3 1/2-year-old girl with a clinical picture of very severe psychomotor retardation, autistic behavior, and repetitive convulsive episodes starting in the neonatal period and resistant to any pharmacological treatment. Electroencephalography showed generalized abnormalities. Magnetic resonance imaging of the brain disclosed arachnoid cysts in both temporal fossae with marked hypoplasia of both temporal lobes. It is proposed that the severity of symptoms is related to the magnitude of underlying anatomical lesions as well as the associated intractable epilepsy. PMID- 8208352 TI - Bilateral, reversible, selective thalamic involvement demonstrated by brain MR and acute severe neurological dysfunction with favorable outcome. AB - We report on two children who presented acute, severe, neurological dysfunction with bilateral, reversible, selective thalamic lesions demonstrated by brain MRI. In both children neurological symptoms appeared two weeks after a febrile respiratory illness. Clinical conditions worsened in a few days to a stuporous state and tetraplegia in one and to coma with decerebrate posturing in the other. Three weeks after the onset, both children improved and recovered within one month. During the acute phase, brain MRI showed in both children bilateral hyperintense areas on T2-weighted sequences limited to both thalamic regions. During the follow-up, repeated brain MRI showed complete disappearance of abnormalities in one patient and a small residual left thalamic lesion in the other. In both patients hematological routine exams were normal. Bacterial and viral studies of serum and CSF were negative. CSF findings showed elevated white blood cell count and protein levels, with no oligoclonal IgG bands. Urine and CSF organic acids by GC/MS and plasma as well as CSF amino acids were normal. We believe that the benign evolution of this disorder and CSF findings strongly suggest a postinfectious process of the central nervous system. PMID- 8208353 TI - Congenital muscular dystrophy with distinct CNS involvement. AB - The sixth child of non-consanguineous parents, who had suffered from severe arthrogryposis syndrome and microcephalia, died at the age of two days. Post mortem study revealed unique morphological brain anomalies characterized by severe cerebral and cerebellar atrophy, focal cerebral mycrogiria and ectopic masses of immature cells in the periventricular region and cerebral white matter; pachygyria was absent. In addition, muscular examination was consistent with severe muscular dystrophy. These findings suggest that new forms of combined cerebral abnormalities and muscular dystrophy of congenital origin can be recognized in isolated cases. PMID- 8208354 TI - Seizures induced by physical exercise: report of two cases. AB - Two children with seizures induced by physical exercise are described. Epilepsy was present from early childhood (age: 4 and 5 months), but the precipitating effect of exercise became evident only later (age: 20 months and 3.5 years). Several treatment regimes were tried, but no satisfactory seizure control could be achieved. In both children no etiological factor was known. MRI, CT and repeated interictal waking and sleeping EEG recordings were normal. Hyperventilation and photostimulation had no effect on the EEG. Physical exercise (e.g., playing football) induced clinical seizures and generalized epileptiform EEG abnormalities as recorded by ambulatory cassette EEG (Oxford). Cardiac arrhythmias were excluded by concomitant EEG recording. Extensive metabolic and endocrinologic investigations during and after seizure induction gave normal results. Thus, the pathophysiologic mechanism for exercise-induced seizures remained unclear. PMID- 8208355 TI - Vigabatrin in newly diagnosed infantile spasms. PMID- 8208356 TI - Vigabatrin for refractory partial seizures in children with tuberous sclerosis. PMID- 8208357 TI - Antiphospholipid antibodies in cerebrovascular ischemia and stroke in childhood. AB - We report on eight children who suffered from cerebrovascular ischemia or stroke at the age of 2 or up to 11 years. Antiphospholipid antibodies (APLA) were detected in two cases during the ischemic event and in six cases during follow-up examinations (after six weeks or within a span of six years). In two patients multiple stenoses of basal cerebral arteries were found; one of them suffered from moyamoya syndrome. The acute hemiplegia in one patient was linked to an asymptomatic mycoplasmal infection and APLA. In three cases, one of the parents was also APLA-positive. Seven patients were treated with acetylsalicylic acid, and in four cases immunoglobulin infusions were given. Transient ischemic attacks subsided after the child with the moyamoya syndrome received immunoglobulins. No effect of medication could be established in the other children. The concept of the antiphospholipid syndrome is still evolving. As none of the common risk factors pertaining to strokes in adults apply to children, pediatric research may offer a suitable platform for specific investigations on the causal, pathogenetic role of APLA. We propose that all children suffering from stroke or transient ischemic attacks should be tested for APLA. PMID- 8208358 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 8208359 TI - Dexamethasone down-regulates endothelin receptors in human cerebromicrovascular endothelial cells. AB - Human cerebromicrovascular endothelial cells (HBEC) in culture express high affinity ETA receptors coupled to phospholipase C activation. Pretreatment of HBEC with 1 microM dexamethasone for 24 h decreased the number of the ET-1 binding sites (Bmax) on HBEC (96 fmol/mg protein vs 57 fmol/mg protein) without changing the binding affinity (KD) (101 pM vs 92 pM) or displacing profile (ET-1 = ET-2 > ET-3 > S6c). Dexamethasone-pretreated HBEC also exhibited a 40% reduction in the maximal ET-1-stimulated inositol triphosphate (IP3) production, whereas half-maximal stimulatory concentration (EC50) was not affected. This effect of dexamethasone was concentration-dependent, and most pronounced after 24 h of pretreatment. The inhibitory effect of dexamethasone on the ET-1-induced IP3 production was abolished by glucocorticoid-receptor antagonist cortexolone. In contrast, vasopressin-mediated IP3 response in HBEC was not changed by dexamethasone. Cyclo-oxygenase inhibitors indomethacin and acetylsalicylic acid did not influence the ET-1-induced IP3 production by HBEC. The down-regulation of ETA receptors in HBEC by dexamethasone, may represent one of the mechanisms involving the described effects of glucocorticoids on cerebromicrovascular function (i.e. changes in blood brain barrier properties, secretion of vasoactive factors, vascular morphogenesis). PMID- 8208360 TI - Effects of vasoactive intestinal peptide (VIP) on scopolamine-induced amnesia in the rat. AB - The effects of vasoactive intestinal peptide (VIP) on spatial cognitive deficits induced in the rat by injections of scopolamine were examined in a radial arm maze. A single intraperitoneal (i.p.), subcutaneous (s.c.) or intracerebroventricular (i.c.v.) injection of VIP inhibited the reduction in the number of initial correct responses in rats with scopolamine-induced amnesia. The inhibition was associated with a bell-shaped dose-response curve. Thus, VIP appears to have an ameliorating effect on spatial cognitive deficits induced by scopolamine in the rat. PMID- 8208361 TI - In vitro expression of calcitonin gene-related peptide in human endothelial cells transfected with plasmid and retroviral vectors. AB - Introduction of cDNA encoding human alpha-calcitonin gene-related peptide (CGRP), a potent vasodilator, into cultured human umbilical vein endothelial cells (HUVEC) was undertaken by using plasmids and retroviral vectors. In order to improve expression, modification of context coding sequence for the initiation of CGRP translation and deletion of nontranslated regions of CGRP cDNA in the transfection vectors were tested. Stable transfer of neo in the HUVEC was achieved with both plasmid and retroviral vectors. Integration rates obtained by using retrovirus (approximately 1%), where higher than those achieved with plasmid-mediated transfection (< 1/1000). CGRP expressed in the transfected HUVEC was secreted into culture medium when a leading sequence was included in the expression vectors. CGRP was detected by enzyme-linked immunosorbent assay (ELISA) in the supernatants of both transiently transfected and stably transfected/infected HUVEC. Higher levels of expression were achieved by using plasmid (giving a maximum CGRP concentration of 6.5 +/- 0.5 pM in the supernatant) than retroviruses. Lipofectin-mediated transfer of CGRP cDNA also resulted in transient expression of CGRP in the HUVEC. PMID- 8208362 TI - Effects of central angiotensin II and angiotensin III on baroreflex regulation. AB - In the present study the cardiovascular effects of intracerebroventricularly (i.c.v.) applied angiotensin II (AN II) and angiotensin III (AN III) were analysed in conscious Wistar rats. The baroreceptor heart reflex (BHR) was elicited by intravenous bolus injection of both phenylephrine (1 microgram) and sodium nitroprusside (5 micrograms) before and after i.c.v. administration (1.5 and 15 min) of the peptides. Administration of 20 ng and 200 ng AN II produced a short increase in inter-beat interval (IBI) and a long-lasting increase in mean blood pressure (MBP), inclusive of a drinking response. Only after the high dose of 200 ng AN II we found a continuous impairment in the BHR for reflex bradycardia. Inversely, the small doses of both 100 pg AN II and 100 pg AN III were without effects on IBI and MBP; they induced an enhancement in BHR for the reflex bradycardia and after 100 pg AN II it was also found for the reflex tachycardia. Pretreatment with 20 nmol amastatin (AM), a specified aminopeptidase A inhibitor, followed by 100 pg An II suppressed the enhancement in BHR. AM alone was without effects in this respect. These findings suggest that: 1) the influence of central angiotensin on the BHR could be dose-dependent in the opposite way and 2) AN III seems to be the active form and involved in the central blood pressure regulatory mechanism. PMID- 8208363 TI - Identification of a novel endothelin receptor in Xenopus laevis liver. AB - Membranes prepared from Xenopus liver displayed high density of high affinity endothelin (ET) binding sites. These sites have the same affinity for [125I] ET-1 and [125I] ET-3. Scatchard analysis of the specific binding from saturation binding experiments revealed an apparent dissociation constant (Kd) of 93.1 and 70.9 pM and maximum binding (Bmax) of 602 and 651 fmol/mg protein for [125I] ET-1 and [125I] ET-3, respectively. Competition binding experiments using [125I] ET-1 and unlabelled ET-1, ET-3, S6c, and BQ123 indicated that ET-1 and ET-3 were the most potent in displacing [125I] ET-1 binding from these membranes (IC50 1 and 0.3 nM, respectively), whereas S6c BQ123, selective for ETB and ETA receptors, respectively, did not have any inhibitory effect up to 1 microM. These data clearly indicate that the ET receptors present in Xenopus liver membranes belong to a new subtype of ET receptor. Because it resembled mammalian ETB receptors in its affinities for ET-1 and ET-3, we propose that this receptor be called the ETBX receptor. PMID- 8208364 TI - Isolation and characterization of peptides derived from the cleavage of the cytoplasmic domain of synaptophysin in frog brain. AB - Three overlapping peptides have been isolated from the whole brain of the European green frog, Rana ridibunda and identified as fragments of the cytoplasmic domain of the synaptic vesicle membrane protein, synaptophysin. The primary structures of the peptides define the amino acid sequence of the 58 residues at the COOH-terminus of the protein and indicate that fragments arose from proteolytic cleavages at the COOH-terminal side of aspartyl residues. The overall conservation of structure of the cytoplasmic domain between the mammalian and amphibian proteins is relatively poor (58% sequence identity between frog and rat synaptophysin). However, the pattern of repeating tyrosine residues that is present in mammalian and Torpedo synaptophysins is also found in the frog protein suggesting that this structural motif is necessary for the, as yet unknown, function of the protein. The cytoplasmic region of frog synaptophysin is also rich in glutamine and glycine residues, but the putative consensus repeating sequence Tyr-Gly-Pro/Gln-Gln-Gly in mammalian synaptophysins does not occur in the frog protein. The data raise the possibility that synaptophysin, like the chromogranins and secretogranin II, may function as the precursor of biologically active peptides. PMID- 8208365 TI - Inhibition of pro-cholecystokinin (CCK) sulfation by treatment with sodium chlorate alters its processing and decreases cellular content and secretion of CCK 8. AB - Pro-cholecystokinin (CCK) has three sulfated tyrosine residues. Sulfation of the tyrosine residue in CCK 8 is known to be important for its activity at CCK A receptors. The role of these sulfated tyrosines in the sorting and processing of pro-CCK was examined by treatment of CCK-secreting rat thyroid medullary carcinoma cells with 10 nM sodium chlorate (a non-toxic inhibitor of tyrosine sulfation). This treatment caused a 50% decrease in the cellular content of immunoreactive CCK and an 80% decrease in its secretion. Sephadex G-50 chromatography of cellular extracts and culture media showed a selective depletion of CCK 8. There was a comparative sparing of CCK 33 and larger molecular forms in cellular extracts which was not observed in the media. These results suggest that the sulfation of the tyrosines of pro-CCK is clearly important for the correct sorting and/or processing of pro-CCK. The pattern of immunoreactive CCK peptides seen with chlorate treatment is consistent with the substrate specificity of a recently identified putative CCK cleaving enzyme and suggests that unsulfated pro-CCK is not efficiently processed to CCK 8 in vivo. The large decrease in CCK content and secretion observed with sodium chlorate may also be due to inefficient sorting of unsulfated pro-CCK into secretory vesicles. PMID- 8208366 TI - Immunoassays for measurement of chromogranin A and pancreastatin-like immunoreactivity in humans: correspondence in patients with neuroendocrine neoplasia. AB - Chromogranin A (CgA) is a useful marker of neuroendocrine tumors in humans. Here we describe and compare two immunoassay methods for determination of CgA, a radioimmunoassay (RIA) and an enzyme linked immunoassay (ELISA). The detection limit of the ELISA was lower than that of the RIA method (2 ng/ml versus 10 ng/ml, respectively), though the CgA RIA method covered a wider range than the CgA ELISA (10-920 ng/ml versus 2-500 ng/ml, respectively). There was no cross reactivity with synthetic human and porcine pancreastatin (PST) in the two assays. There was a significant positive correlation between levels of CgA in sera from patients with carcinoid disease, measured by the two methods (r = 0.9, p < 0.0001), and the values were in the same range. Similarly, serum CgA levels in normal controls were also in the same range when assayed by the two methods. A commercially available porcine PST RIA method was evaluated, especially with respect to the influence of Sep-Pak extraction of serum on the levels of pancreastatin-like immunoreactivity (PST-LI). Ten sera from carcinoid patients were treated with Sep-Pak extraction, and levels of PST-LI were determined in non extracted and extracted sera. There was a significant positive correlation between the concentrations of PST-LI measured in extracted and non-extracted carcinoid sera (r = 0.9, p < 0.002), and the levels were in the same range. There was also a significant positive correlation between levels of CgA and PST-LI in 49 carcinoid sera (r = 0.8, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208367 TI - Regulation of feeding by multiple opioid receptors in cingulate cortex; follow-up to an in vivo autoradiographic study. AB - A previous in vivo autoradiographic study demonstrated reduced 3H-diprenorphine binding in anterior cingulate cortex of rats that were injected (i.v.) with the radiolabeled opiate during lateral hypothalamic stimulation-induced feeding (SIF). This suggests that an opioid peptide is released in cingulate cortex during feeding and excludes binding of the tracer. The aim of the present study was to determine whether opioid activity in cingulate cortex contributes to the expression of SIF. Agonists and antagonists for multiple opioid receptors were microinjected into cingulate cortex and effects on stimulation frequency threshold for SIF were determined. Although the universal opioid antagonist naloxone (20.0 micrograms) increased threshold, high doses of selective antagonists for mu, delta, and kappa receptors--D-Tic-CTAP, natrindole and norbinaltorphimine, respectively--had no effect. The unique efficacy of naloxone may be due to this lipophilic compound's rapid diffusion throughout an extensive volume of anterior cingulate tissue. While high doses of the kappa agonist U50,488 and the delta agonist DPDPE had no effect, the mu agonist, DAGO (1.0 microgram), decreased the SIF threshold. Moreover, the threshold-lowering effect of DAGO was blocked by pretreatment with the irreversible mu antagonist beta-FNA. These results suggest that mu opioid activity in cingulate cortex can facilitate SIF but that under basal conditions endogenous opioid activity in this brain region makes only a small positive contribution, if any, to the expression of SIF. PMID- 8208368 TI - Calcitonin genes (I and II) expression in human nervous and medullary thyroid carcinoma tissues. AB - The calcitonin gene family comprises two main genes: CALC I which encodes for calcitonin (CT) mRNA in thyroid and calcitonin gene-related peptide I (CGRP I) mRNA in neuronal tissues and CALC II gene which encodes for CGRP II mRNA only. Recently, in normal thyroid and in medullary thyroid carcinoma (MTC), we detected an additional splicing pathway involving the splicing of exon 4 to exon 5 and leading to the expression of a third CALC I mRNA: CT mRNA II. In the present study, we analyzed by polymerase chain reaction the expression of CT mRNAs I and II, CGRP I and II mRNAs in MTC and in human tumors of the nervous system (3 pituitary adenomas, 3 astrocytomas, 2 schwanomas). In pituitary tissues, CGRP II expression was constant and easily detectable in comparison to other tissues. CT mRNA II signal was very low, but clearly detectable after a reamplification indicating that the factors responsible for the splicing of exon 4 to exon 5 are poorly operative in neuronal tissues. PMID- 8208369 TI - The long path of the snail. PMID- 8208370 TI - Protein metabolism in the formation of the conditioned avoidance reflex of molluscs. PMID- 8208371 TI - Dynamics of defense and feeding conditioned reactions in the snail during long term sensitization. AB - An intensification of the defense reaction and a significant decrease in the consumption of food take place, the development of the defense conditioned reflex is facilitated, and the development of the feeding reflex deteriorates in the snail in the presence of long-term sensitization. The results suggest that the formation of the state of long-term sensitization is accompanied by the formation of a dominant defense focus. PMID- 8208372 TI - Facilitation of defense reactions during the consumption of food in snails: the participation of glucose and gastrin/cholecystokinin-like peptide. AB - The molecular-cellular mechanisms of the interrelationships between the alimentary and defense behavior of snails were investigated. The clarity of manifestation of defense reactions at various stages of the satisfaction of alimentary need was studied. It was found that the defense reactions were attenuated in starved molluscs, whereas after a 20-minute feeding session the facilitation of generalized defense reactions takes place, the clarity of manifestation of which depends on the duration of food deprivation. It was demonstrated that an increase in the level of glucose in the hemolymph of the starved molluscs to the level present in the hemolymph during a meal (1.6-2.0 mM), as well as the administration of 20-30 ng of analogs of gastrointestinal peptides (pentagastrin or cholecystokinin octapeptide, CCK-8) elicits the facilitation of generalized defense reactions similar to that found during the feeding of the snails. The directionality of the changes in the activity of the L RPl1 neurons during the application of carrot juice to the lip of semi-intact preparations of starved snails depended on the presence of glucose in the solution bathing the central nervous system. Similar glucose-dependant changes were found after the application of CCK-8 to the CNS of starved snails, but not of FMRFamide, whereas the isolated application of glucose did not exhibit such an effect. It was found that the L-RPl1 neurons were the most sensitive to the change in the concentration of glucose and CCK-8 in the perfusate. The adaptive significance of the dependance of the clarity of manifestation of defense reactions on the level of alimentary need of the snails and the participation of glucose and gastrin or cholecystokinin-like peptide in these processes are discussed. PMID- 8208373 TI - Mechanisms of the development of sensitizations in the snail: the participation of calcium and calmodulin. AB - A single sensitizing exposure led to brief (up to 1 h) and prolonged (several hours) changes in the defense reactions of snails, in the activity of command neurons, as well as in the content of bound calcium in these neurons. The application of the specific calmodulin blocker, W7, or the removal of Ca2+ from the medium bathing the snail's CNS before the sensitizing exposure, exerted a suppressant influence on the development of both the brief and the prolonged behavioral and neuronal effects of sensitization. At the same time, the application of W7 or the removal of Ca2+ following the application of the sensitizing influence did not suppress the development of the prolonged changes in the command neurons. The data obtained make it possible to assume that calmodulin directly participates in the regulation of the membrane and synaptic events leading to the development of the brief effects of sensitization. In addition, it is probably involved in the initiation of the metabolic reactions leading to the occurrence of the prolonged effects; however, it does not take part directly in their manifestation. PMID- 8208374 TI - Nervous system and neural maps in gastropod Helix lucorum L. AB - The present review summarizes the literature and provides new data concerning nervous system structure and the identification of individual neurons in the snail Helix lucorum. Information about especially well-known neurons is provided in a table, and maps of the identifiable neuron's location in ganglia are correlated with the results of retrograde staining via various cerebral and subesophageal nerves. References concerning the morphology of snail central nervous system and identifiable neurons are given. PMID- 8208375 TI - Conditioning and sensitization in the snail: neurophysiological and metabolic characteristics. AB - The changes in the electrophysiological indices as well as the intravital dynamics of the content of bound calcium (Cab) during the development of sensitization and of food aversion conditioned reflex were investigated in the command neurons of the snail. The most essential electrophysiological distinction of conditioning from sensitization was the later appearance of the response to the conditional stimulus as compared with the emergence of long-term sensitization: the facilitation of the responses of the neuron to test sensory stimulations appeared 50-60 min after the application of the first sensitizing stimulation, whereas the reaction to the conditional stimulus appeared 30 min later. The analysis of the dynamics of Cab suggests that the differences in the electrophysiological effects may be associated with the pronounced differences in calcium-dependent metabolism during the development of these acquired capacities. PMID- 8208376 TI - Cholinoreceptor neurons of the snail: identification, plasticity, and its regulation by opioids and second messengers. AB - A review of the author's own data on the cholinoreceptors of identified neurons of the snail and the regulation of their plasticity. The following sections are presented: the identification of the cholinoreceptors; the coupling of the cholinoreceptors with ion channels; the identification of the opioid receptors; the modulation by opioids of the activity of the cholinoreceptors; the plasticity of the cholinoreceptors; the regulation of the plasticity of the cholinoreceptors by opioids; the regulation of the plasticity of the cholinoreceptors by second messengers; the second messengers involved in the regulation of the plasticity of the cholinoreceptors by the opiate kappa agonist, bremazocine. PMID- 8208377 TI - Influence of oxytocin on identified neurons of the brain of the snail Helix pomatia L. AB - The responses of identified neurons induced by the effect of perfusion with a solution of oxytocin were investigated in this study. Depolarizing, hyperpolarizing, and modulating types of responses were found. It is hypothesized that these responses are associated in the majority of instances with the system of cyclic nucleotides. PMID- 8208378 TI - Identified neuronal individuals in the buccal ganglia of Helix pomatia. AB - The buccal ganglia of Helix pomatia are used as model nervous structures in neurophysiological and epileptological studies. Many basic problems concerning membrane physics and the functioning of single neurons and neuronal networks can be easily studied using these ganglia. The model character derives mainly from the relative simplicity of this nervous system and the fact that it contains large, visually identifiable neurons. As in other invertebrate nervous systems, the large neurons have proved to be individuals showing the same functional and structural properties from one animal to another. PMID- 8208379 TI - Mapping of neurons participating in the innervation of the body wall of the snail. AB - The results of experiments on the retrograde staining of the left-sided cutaneous nerves of the pedal ganglia of the snail Helix lucorum L. are presented in this paper. The bodies of nerve cells contributing processes to these nerves were identified by means of the precipitation of nickel and cobalt ions by rubeanic acid. A large number of neurons were found, including the parietal command neurons, in all the ganglia, with the exception of the buccal. An especially large number of neurons were stained in the ipsilateral pedal, pleural, and parietal ganglia. PMID- 8208380 TI - Newly identified nerve cells of the snail, Helix pomatia, associated with the generation of pacemaker activity. AB - Data on new, previously unidentified nerve cells of the snail Helix pomatia are presented in this paper. The identified neurons described may serve as a convenient model for the investigation of the cellular mechanisms of pacemaker activity, the role of neuropeptides in the generation and regulation of pacemaker activity, peptidergic transmission, and the functional role of the inward calcium current. PMID- 8208381 TI - Structural organization of the sensory systems of the snail. AB - The author's data on the structural organization of the nervous system of the body wall, the gravitational organs (the statocysts, the eyes, and the chemosensory organs), and the head tentacles of the snails Helix vulgaris and Helix pomatia are correlated in this paper. The localization in the CNS and some structural characteristics of the central divisions of the sensory systems are shown. Information is presented on the structure of the procerebrum, an associative center participating in the processing of chemosensory information. The data were obtained using the Golgi method, the retro- and anterograde transport of CoCl2, horseradish peroxidase, and lucifer yellow, as well as a number of other classical histological methods. PMID- 8208382 TI - The architecture of the reflex arc. AB - The identification of local detectors, command neurons, and modulator neurons has opened up the possibility of the structural identification of individual synaptic contacts supporting the functioning of the reflex arc. Nonassociative plasticity (habituation and sensitization) are [sic] realized at the level of the receptors and potential-dependent calcium channels through dephosphorylation phosphorylation of receptor and channel proteins. Associative plasticity (the development and extinction of the conditioned reflex) includes two levels of regulation: short-term (through dephosphorylation-phosphorylation of receptor and channel proteins) and long-term (through the expression of genes coding structural and translocational genes). Its selectivity is an extremely important characteristic of associative plasticity. The mechanism of associative plasticity is based on the principles of the Hebb plastic synapse, supplemented by indication of the role of nonspecific (modulating) influences. PMID- 8208383 TI - The vision of the snail: the spectral sensitivity of the dark-adapted eye. AB - The spectral sensitivity of the dark-adapted eye of the snail Helix lucorum L. was investigated in semi-intact "optic cupoptic nerve-cerebral ganglion" preparations. The data of the recording of the electroretinogram in response to monochromatic radiation of varied intensities were used to plot the spectral sensitivity functions. The averaged spectral sensitivity function is well described by a Dartnall nomogram for the photopigment rhodopsin with a sensitivity peak at 496 nm. PMID- 8208384 TI - Avoidance behavior of the snail. AB - In the present article previously published and novel data are reviewed concerning the organization of avoidance behavior of snails of the genus Helix. Musculature participating in the behavior is described, and neural networks controlling the muscles are considered. PMID- 8208385 TI - Mono- and polysynaptic connections between identified neurons in the system of the passive avoidance reflex of the snail. AB - The structure of the synaptic connections between identified sensory and giant command neurons of the parietal ganglia of the snail is examined. It is shown that the excitatory postsynaptic potential arising in the giant neuron in response to the generation of a single action potential in the presynaptic neuron consists of several monosynaptic components and may include polysynaptic components. It is hypothesized that monosynaptic components of the elementary excitatory postsynaptic potential that differ in the duration of the latent period and the dynamics of habituation may be associated with the activation of synaptic buttons on axon terminals of varying length. PMID- 8208386 TI - Processing of mechano- and chemosensory information in the lip nerve and cerebral ganglia of the snail Helix pomatia L. AB - Neurophysiologists have long been seeking simple model systems in which to analyze the neuronal mechanisms underlying the organization of behavior. The feeding behavior of molluscs has proved to be one of the most useful simple systems for the analysis of cyclical motor patterns, the interactions of central pattern generating interneurons, and the role of sensory inputs in the initiation and maintenance of the behavior. Considerable progress has been made in one or both of the first two aspects of this research in Lymnaea, Helisoma, Limax, Planorbarius, Pleurobranchaea, and Tritonia (for reviews see [3, 7, 8, 15]), and more recently, in Aplysia [39] and Planorbis [1]. The role of mechano- and chemosensory inputs in the organization of the feeding behavior was studied in at least twenty molluscan species (for a review see [3]). However, in only less than half of them was the analysis extended to the effect of tactile and chemical inputs on identified neurons in the buccal and cerebral ganglia which contain the feeding circuitry (Aplysia: [12, 22, 36, 41]; Pleurobranchaea: [9, 16, 17]; Tritonia: [2]; Helisona: [21]; Limax: [11, 14, 35]: Helix: [6, 19, 24-26, 32, 38]). In the present work I would like to review our earlier findings on the processing of mechano and chemosensory information in the lip nerves and cerebral ganglia of Helix pomatia L. These findings were published in a series of papers between 1982 and 1987 [19, 20, 24-26]. The results reviewed here prepared the way for the development of new lines of research in our laboratory on the plasticity and serotonergic modulation of feeding in this widely used experimental animal [27, 40]. PMID- 8208387 TI - Viscerocardiac reflexes of the snail. AB - The viscerocardiac and cardiocardiac reflexes in the snail are effectuated by just two inhibitory motoneurons of the visceral ganglion. The neurons are switched on in parallel and have extensive, partially overlapping receptive fields. Due to the high degree of sensitivity of the nerve endings of these cells to mechanical stimuli, the inhibitory motoneurons of the heart perform an afferent function at the same time. A morphological analysis of the inhibitory neurons demonstrated their identity to the previously identified V21 multimodal interneuron. PMID- 8208388 TI - Behavioral plasticity in a snail and its neural mechanisms. AB - This paper reviews the behavioral and neural mechanisms of habituation, sensitization, environmental condition, and food-aversion conditioning in the snail helix. The possible participation of motivational systems and changes in plasticity during development are discussed. PMID- 8208389 TI - Cerebrovascular abnormalities in neurofibromatosis type 1. PMID- 8208390 TI - 'Sympathetically maintained pain.' I. Phentolamine block questions the concept. AB - Patients with "reflex sympathetic dystrophy" or "causalgia" underwent sympathetic blocks. In protocol A (77 patients), we infused placebo (saline) for 30 minutes followed by phentolamine (35 mg). In protocol B (23 patients), the saline phase was followed by double-blind infusion of phentolamine or phenylephrine (500 micrograms), a second phase of saline, and then the other active drug. We assessed magnitudes of pain and mechanical hyperalgesias on a 0-to-10 pain scale and monitored sensory and sympathetic effects. With protocol A, pain diminished significantly (> or = 50%) during placebo in 22 patients (28.9%) and during phentolamine in seven (9.2%). With protocol B, four patients (17.3%) had relief of pain during placebo, four (17.3%) during phenylephrine, and two (8.7%) during phentolamine. All "phentolamine responders" had progressive pain relief from placebo. Two patients expressed relief during phenylephrine and worsening during phentolamine. Most patients did not respond significantly to saline or drugs. Thus, pharmacologic manipulation of the alpha-1 adrenergic receptor by either agonist or antagonist drug does not influence neuropathic pains. These results raise questions about the existence of "sympathetically maintained pain," as diagnosed by sympathetic blocks improperly controlled for placebo. PMID- 8208392 TI - Progressive supranuclear palsy: neuropathologic and clinical heterogeneity. AB - To investigate potential heterogeneity in progressive supranuclear palsy (PSP), we examined 13 patients with neuropathologically diagnosed PSP. The clinical diagnosis of PSP was made in eight of these individuals, whereas probable AD was the primary diagnosis in the remaining five. In addition to PSP neuropathology, seven of the 13 patients (54%) showed concomitant pathologic changes of Alzheimer's disease (AD), Parkinson's disease (PD), or both disorders. These observations indicate that AD and PD changes coexist with PSP neuropathology in a substantive proportion of patients and provide further evidence of clinical and neuropathologic heterogeneity in neurodegenerative disorders. Moreover, our results suggest that PSP may be underdiagnosed and deserves more prominence in the differential diagnosis of dementing illness. PMID- 8208391 TI - Phentolamine sympathetic block in painful polyneuropathies. II. Further questioning of the concept of 'sympathetically maintained pain'. AB - To test for the presence of "sympathetically maintained pain" (SMP), we administered placebo-controlled phentolamine sympathetic blocks to 14 patients with painful polyneuropathies. Six received i.v. infusion of saline for 30 minutes, followed by phentolamine (35 mg). In eight patients, the saline phase was followed by double-blind infusion of phentolamine or phenylephrine (500 micrograms), a second saline phase, and then the other active drug. We measured magnitudes of spontaneous pain and mechanical hyperalgesias on a 0-to-10 pain scale every 5 minutes and monitored sensory and sympathetic effects clinically and through quantitative thermotest and thermography. Five patients reported significant diminution of pain (> 50%), all in response to placebo. Neither phentolamine nor phenylephrine provided relief, although all patients had signs of physiologic abnormalities reputed to be determinants or predictors of SMP. These results complement previous studies demonstrating the nonexistence of SMP among "reflex sympathetic dystrophy" patients and further question the concept of SMP. PMID- 8208393 TI - The syndrome of 'pure akinesia' and its relationship to progressive supranuclear palsy. AB - Five patients developed a stereotyped syndrome of progressive akinesia of gait, speech, and hand-writing without rigidity, tremor, or dementia. The symptoms did not improve with levodopa. These clinical findings conform to a syndrome described repeatedly in Japan since 1974 as "pure akinesia." Evidence has indicated that pure akinesia often represents a pre-ocular motor, and in some cases an ocular motor-sparing, form of progressive supranuclear palsy (PSP). Although we found disorders of eyelid movements, none of the patients demonstrated a gaze palsy on clinical examination. Four patients underwent eye movement recordings. The two patients with the longest disease duration had slow or small vertical saccades. These findings support the notion that patients with pure akinesia may develop a vertical gaze palsy, similar to that in PSP, late in their course. Our patients show that pure akinesia occurs in North America as well as in Japan. Recognition of the syndrome of pure akinesia may suggest the diagnosis of PSP before the development of abnormalities of ocular movement. PMID- 8208395 TI - Uhthoff's symptom in disorders of the anterior visual pathways. AB - To determine the frequency and clinical characteristics of Uhthoff's symptom, I studied 100 consecutive patients with pregeniculate visual loss of diverse etiology. Eighteen patients reported Uhthoff's symptom. Although there was a significant association of Uhthoff's symptom with multiple sclerosis (10 patients), other etiologies for this symptom included tumor (3 patients), optic neuropathy or papillitis (3 patients), aneurysm, and orbital pseudotumor (1 patient each). There was no link between the severity of visual loss, as measured by diminished acuity, field loss, or binocular involvement, and Uhthoff's symptom. PMID- 8208394 TI - Medical treatment of Rasmussen's syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients. AB - We treated 19 patients with Rasmussen's syndrome (chronic encephalitis and epilepsy)--a rare progressive disorder of unknown etiology causing focal epilepsy, hemiparesis, and intellectual deterioration--with intravenous immunoglobulins, high-dose steroids, or both, to control seizures and improve the end point of the disease. Ten of 17 patients receiving steroids, and eight of nine patients receiving immunoglobulins, had some reduction of seizure frequency in the short term. Improvement in hemiparesis was slight. The effect of these drugs in ameliorating the end point of the disease in the long term remains unknown, and further multicenter studies with standardized protocols are warranted. PMID- 8208396 TI - Magnetic resonance imaging analysis of age-related changes in the brains of individuals with Down's syndrome. AB - Neuroanatomic characteristics of the brains of individuals with Down's syndrome (DS) are typically characterized at autopsy. Apparent anatomic differences in brain between DS and normal individuals are observable upon gross inspection of MRIs. Area measurements from coronal MRIs are used in this study to determine quantitative structural differences that may occur in DS and during aging. In DS individuals, a significantly larger parahippocampal gyrus, and smaller hippocampus and neocortex, are reported relative to age-matched controls. We also examine two DS individuals with a clinical diagnosis of dementia who exhibit atrophy similar to that typically observed in Alzheimer's disease. MRI appears to be a useful tool for quantitative anatomic analysis and may be beneficial for determining baseline anatomic measures that can be useful in the diagnosis of changes associated with dementia. PMID- 8208397 TI - Precursors of extracranial carotid atherosclerosis in the Framingham Study. AB - To investigate cardiovascular risk factors and carotid atherosclerosis, we related previously measured risk factors to carotid atherosclerosis as determined by duplex ultrasonography in the Framingham Study cohort. Risk factors measured prospectively on 1,116 cohort members, ages 66 to 93, were related to the severity of carotid atherosclerosis measured by carotid ultrasonography performed during biennial examination no. 20 (1988 to 1990). The degree of carotid atherosclerosis was expressed as a percent carotid stenosis and, for statistical analysis, subjects were divided into four groups according to percent carotid stenosis. The prevalence of significant carotid stenosis in the general population was low--7% in women and 9% in men. A multivariate logistic regression model showed that age, cigarette smoking, systolic blood pressure, and cholesterol were independently related to carotid atherosclerosis. Alcohol consumption was also significant in men, but not in women. In addition, our results indicate that both current and former smoking in both sexes was related to the degree of carotid atherosclerosis. PMID- 8208398 TI - Parkinsonism caused by petroleum waste ingestion. AB - A 20-year-old laborer developed moderate parkinsonism 1 week after accidentally ingesting a petroleum waste mixture. Parkinsonism persisted for 3 months and then began to improve, although subtle signs remained 29 months after exposure. 6 Fluorodopa-labeled positron emission tomography (6-FD PET) performed 3 months postexposure revealed a striatal dopamine rate constant level of 0.170 ml/striatum/min, nearly 3 SD below the mean for age-matched controls. However, subsequent PETs demonstrated 6-FD PET rate constants not significantly different than controls. Although the causative agent has not yet been identified, this case suggests that compounds capable of causing parkinsonism may exist in commonly used petroleum products. PMID- 8208399 TI - The effects of 4-aminopyridine in multiple sclerosis patients: results of a randomized, placebo-controlled, double-blind, concentration-controlled, crossover trial. AB - Because 4-aminopyridine (AP) improves residual deficits in some multiple sclerosis (MS) patients but has a narrow toxic-to-therapeutic margin, we compared the safety and efficacy of two target peak serum concentration ranges (low: 30 to 59 ng/ml and high: 60 to 100 ng/ml). We enrolled eight MS patients with temperature-sensitive visual and motor deficits in a randomized, placebo controlled, double-blind, crossover trial of short-term oral AP treatment. We randomized patients to a sequence of three treatments on three separate days: placebo, low serum concentration, and high serum concentration. We determined dosing to achieve the desired steady-state peak serum concentration ranges from a test dose and population pharmacokinetic parameters using bayesian estimation. Contrast sensitivity, standard neurologic examination, ratings of videotaped neurologic examinations, and quantitative strength assessment all improved with treatment, but flicker fusion frequency, visual evoked response latencies, and Expanded Disability Status Scale scores did not. All patients experienced side effects during the high-serum-concentration arm. A grand mal seizure occurred at a serum AP level of 104 ng/ml, and an acute confusional episode occurred at 114 ng/ml. AP treatment produced improvements in residual deficits in MS patients, but the occurrence of significant toxicity suggests that AP serum levels should be monitored and peak levels above 100 ng/ml should be avoided. Concentration control methodology may be useful in testing putative treatments for other neurologic diseases. PMID- 8208400 TI - Distribution in time of seizures during presurgical EEG monitoring. AB - We studied the length of stay needed to record a certain number of seizures in a highly selected group of patients with intractable epilepsy in the final stages of presurgical monitoring. The mean length of stay needed to record one seizure was 2.9 to 3.7 days, depending on the recording technique, 4.5 to 5.5 monitoring days to record three seizures, and 6.1 to 7.6 days to record five seizures. It took 5 days to record at least one seizure in 90% of patients, 7 to 10 days to record three seizures, and 8 to 12 days to record five seizures. One-third of all patients had fewer than five seizures during their stay. Extrapolating from the results in our unit, we computed a need for 91 to 227 presurgical epilepsy monitoring beds to evaluate 2,000 to 5,000 similar epilepsy surgery candidates requiring invasive monitoring in the United States each year. Additional beds would be needed to monitor patients admitted for other purposes. PMID- 8208401 TI - Initial and follow-up brain MRI findings and correlation with the clinical course in Wilson's disease. AB - We performed pretreatment brain MRIs in 25 patients with neurologically symptomatic Wilson's disease (WD) and clinical and MRI follow-up in 16 of them. All 25 pretreatment MRIs revealed abnormalities, with abnormal high-signal intensity (HSI) in bilateral thalami being the most common (92%). HSI lesions in the brainstem (84%) and the basal ganglia (72%) were also common. Brain atrophy was present in 88% of the 25 patients. In the follow-up period of 5 to 24 months, during which the patients were treated with D-penicillamine, both HSI lesions and neurologic symptoms improved in 88% of the 16 patients, but the brain atrophy did not change. PMID- 8208402 TI - Lateralization of memory for the visual attributes of objects: evidence from the posterior cerebral artery amobarbital test. AB - We used the posterior cerebral artery amobarbital test to examine how each temporal lobe mediates memory for objects. Temporal lobectomy candidates were presented with four objects while one hemisphere was anesthetized. We assessed recall and recognition following recovery from the drug. Verbal recall was significantly better following object presentation to the left hemisphere when the left hemisphere was not the seizure focus. Recognition memory, tested with two identical objects, two objects that shared the same name but had different physical characteristics, and two foils, was superior following object presentation to the right hemisphere. Only the right hemisphere could discriminate identical objects from same-name foils. These data confirm that the left temporal lobe has an advantage in encoding the verbal representation of an object and suggest that the right temporal lobe is critical for memory of specific visual attributes of objects. PMID- 8208403 TI - Late-onset drop attacks in temporal lobe epilepsy: a reevaluation of the concept of temporal lobe syncope. AB - We report the clinical, radiologic, and EEG features of six patients with temporal lobe drop attacks (TLDA), all of whom underwent temporal resection. Postoperative follow-up of at least 1 year was available in all. TLDA were never the first manifestation but followed the onset of epilepsy after a long delay ranging from 7 to 43 years (mean, 24.4 years). Seizures were of unilateral temporal origin. In one patient, stereo EEG recording of TLDA showed rapid spread of the ictal discharge away from the temporal lobe in less than 1 second. Postoperatively, three patients were seizure free; one has had no TLDA but experiences sporadic auras; another, despite a reduction of more than 50%, continues to have complex partial seizures and TLDA; and the sixth has had sporadic secondarily generalized seizures upon reduction of antiepileptic medication. In conclusion, drop attacks may occur in temporal lobe epilepsy, usually long after the onset of epilepsy. They lead to increased disability and suggest a rapid spread of the ictal discharge and possible involvement of the pontine reticular formation rather than the presence of bitemporal foci or an extratemporal origin. PMID- 8208404 TI - Treatment with D-penicillamine improves dopamine D2-receptor binding and T2 signal intensity in de novo Wilson's disease. AB - We report the results of in vivo striatal dopamine D2-receptor binding assessed by PET using 11C-raclopride (only one patient) and by single-photon emission computed tomography (SPECT) using 123I-iodobenzamide (123I-IBZM) and the findings of T2-weighted MRIs in two de novo Wilson's disease patients before and 4 months after initiation of D-penicillamine treatment. Before treatment, specific 11C raclopride binding (only patient 1) was markedly reduced, with a putamen to cerebellum ratio of 1.99 (controls: 3.99 +/- 0.55, n = 15) and a caudate to cerebellum ratio of 2.52 (controls: 3.65 +/- 0.59, n = 15). Specific 123I-IBZM binding was reduced in both patients, with a basal ganglia to frontal cortex ratio of 1.25 (patient 1) and of 1.41 (patient 2) controls: 1.57 +/- 0.04, n = 5). After 4 months of therapy, 11C-raclopride-PET improved to a putamen to cerebellum ratio of 2.52 and a caudate to cerebellum ratio of 3.06 (patient 1). 123I-IBZM-SPECT revealed an increase of basal ganglia to frontal cortex ratios of 1.34 (patient 1) and 1.55 (patient 2). On heavily T2-weighted MRI sequences, hyperintense signal changes before therapy within the putamen (both patients), brainstem (only patient 1), and caudate (only patient 2) greatly diminished after treatment. Reduced striatal dopamine D2-receptor binding in these Wilson's disease patients improved under therapy, suggesting, in part, a reversible defect of striatal neurons. PMID- 8208405 TI - Turcot's syndrome: evidence for linkage to the adenomatous polyposis coli (APC) locus. AB - OBJECTIVE: To investigate the possibility that neuroepithelial tumors in Turcot's syndrome are caused by pleiotropic mutations in the gene for adenomatous polyposis coli (APC), a tumor-suppressor gene implicated in colonic cancer. METHODS: We studied the inheritance patterns of genetic markers for the chromosome 5q21 region in 12 members of a Turcot's syndrome kindred with five affected members. We performed linkage analysis to detect linkage between the disease phenotype and DNA markers. RESULTS: Marker D5S346, located 30 to 70 kilobases from the APC locus, showed evidence highly suggestive of linkage to the disease phenotype (lod score = 1.92). CONCLUSIONS: The data provide evidence that the tumor-suppressor gene implicated in APC and sporadic colon cancers may also cause malignant neuroepithelial tumors in Turcot's syndrome. PMID- 8208406 TI - Reduced platelet cytochrome c oxidase activity in Alzheimer's disease. AB - We evaluated a simplified method for preparation and analysis of platelet cytochrome c oxidase activity in Alzheimer's disease (AD) and control patients. Mean cytochrome c oxidase activity in controls (n = 17) was 0.233 sec-1/mg whereas mean cytochrome c oxidase activity in Alzheimer patients (n = 19) was 0.193 sec-1/mg, p = 0.033. Complex III (ubiquinol:cytochrome c oxidoreductase), complex II (succinic dehydrogenase), and citrate synthase were all assayed as internal controls and were not significantly different in controls and Alzheimer patients. There is a relatively specific loss of platelet cytochrome c oxidase activity in Alzheimer disease patients. PMID- 8208407 TI - Electron transport chain defects in Alzheimer's disease brain. AB - Previous work suggested a deficiency in the terminal complex of the mitochondrial electron transport chain, cytochrome c oxidase (COX), in platelet mitochondria of Alzheimer's disease (AD) patients. The present study extends this observation to AD brain mitochondria through assay of electron transport chain activities in mitochondria isolated from autopsied brain samples from AD patients (n = 9) and from controls with and without known neurologic disease (n = 8). AD brain mitochondria demonstrated a generalized depression of activity of all electron transport chain complexes. This depression was most marked in COX activity (p < 0.001). Concentrations of cytochromes b, c1, and aa3 were similar in AD and controls. The electron transport chain is defective in AD brain, and the defect centers about COX. PMID- 8208408 TI - Late-onset muscular weakness in phosphofructokinase deficiency due to exon 5/intron 5 junction point mutation: a unique disorder or the natural course of this glycolytic disorder? AB - Late-onset muscle weakness is rare in glycolytic disorders. There are two reports in the literature of phosphofructokinase (PFK)-deficient Ashkenazi Jews with severe vacuolar myopathy manifesting in late adulthood. The genetic abnormality in these patients is unknown. We report a third patient with a similar syndrome: early-onset exercise intolerance in young childhood and progressive weakness in a limb-girdle distribution appearing at 57 years of age, leading to severe incapacity. Muscle histology showed diffuse vacuolar changes, and muscle fibers contained excess glycogen-like material. Muscle biochemistry was diagnostic for PFK deficiency. DNA analysis from the patient and his family showed that he was homozygous for a recently identified point mutation at the exon 5/intron 5 junction (a G-to-A change); two other family members were heterozygous for this mutation. It is not clear whether late-onset weakness is the natural course for all PFK-deficient patients or whether the exon 5 mutation carries increased risk for this severe myopathy. PMID- 8208409 TI - Cortical function in progressive lower motor neuron disorders and amyotrophic lateral sclerosis: a comparative PET study. AB - OBJECTIVE: To compare cortical function at rest and during limb movement in patients with progressive lower motor neuron degeneration (LMND) and amyotrophic lateral sclerosis (ALS). METHODS: PET was used to measure regional cerebral blood flow (rCBF) in five patients with progressive LMND, six patients with classic ALS with a similar degree of motor impairment, and six age-matched control subjects; measurements were taken in the resting state and while subjects moved a joystick with their right hand. RESULTS: rCBF at rest in the primary sensorimotor cortex (SMC) was significantly (p < 0.001) lower in ALS patients than in control subjects or LMND patients. rCBF at rest did not differ significantly between LMND patients and controls. During joystick movement, ALS patients showed significantly (p < 0.001) greater rCBF increases than controls or LMND patients in the hand/arm area of the SMC bilaterally, the face area of the contralateral SMC, the second somatic sensory (SII) cortex bilaterally, and the contralateral premotor and supplementary motor cortices. LMND patients showed significantly (p < 0.001) greater rCBF increases than controls and ALS patients only in the anterior insular cortex bilaterally. CONCLUSIONS: The finding of reduced rCBF at rest, together with abnormal bilateral activation and altered somatotopy during movement, in the sensorimotor cortex of ALS but not LMND patients suggests that these abnormalities reflect loss of pyramidal neurons. Abnormal activation of perisylvian areas (insular and SII cortices) during limb movement in both LMND and ALS patients suggests that these may be accessory sensorimotor areas that are recruited nonspecifically in response to limb weakness. PMID- 8208410 TI - Blood buffy coat from Alzheimer's disease patients and their relatives does not transmit spongiform encephalopathy to hamsters. AB - There was a report of spongiform encephalopathy transmitted to Syrian hamsters by intracerebral inoculation with the blood buffy coat of patients with Alzheimer's disease (AD) and their unaffected first-degree relatives. We attempted to verify that report, taking measures to reduce the risk of contaminating samples with agents causing spongiform encephalopathies. We obtained blood from 50 subjects, including six patients with familial AD, 21 unaffected first-degree relatives (siblings and offspring) of patients with familial AD, and 20 control subjects. We inoculated the buffy coats intracerebrally into Syrian LVG hamsters, observed them for signs of neurologic disease, examined their brains for neuropathologic changes at time of death, and performed serial (blind) passages by inoculating suspensions of all recovered brains into fresh LVG hamsters. We discerned no clinical illness or histopathologic changes resembling experimental spongiform encephalopathy in any hamster inoculated with human buffy coat nor in blind passage hamsters, nor were the life spans of those hamsters shortened. We conclude that AD is not caused by an agent that transmits spongiform encephalopathy to hamsters. PMID- 8208411 TI - Correlation of somatosensory central conduction time with height. AB - To study the correlation between somatosensory central conduction time (CCT) and the subject's height, we recorded somatosensory evoked potentials (SEPs) from the neck and scalp elicited by median nerve stimulation in 72 normal young adults. We determined the CCT in each subject from peak-to-peak and onset-to-onset measurements. The mean value for the onset CCT was 6.2 +/- 0.4 msec and for the peak CCT, 5.7 +/- 0.5 msec. The peak CCT was significantly shorter but showed a wide range. There was a significant correlation between the onset CCT, but not the peak CCT, and height. Our findings confirm that the length of the central somatosensory pathway is proportional to the subject's height and indicate that the "conventional" peak CCT measurement of median nerve SEPs is inadequate. PMID- 8208412 TI - CAG repeat size and clinical presentation in Huntington's disease. AB - The specific mutation in Huntington's disease (HD) is an expansion of the unstable CAG trinucleotide repeat in the IT15 gene in chromosome 4p. We examined the relationship between the CAG repeat size and clinical presentation in 36 patients with suspected diagnosis of HD. Twelve patients had no relatives with documented HD, and five of them failed to show the expanded (>37) CAG repeats. The remaining 31 patients, including seven patients with atypical clinical features for HD (three without and four with family history of documented HD), were heterozygotes for the CAG repeat expansion. There were large CAG repeats (50 copies) in paternally transmitted HD cases with early onset (age 30 or earlier). The rate of disease progression was faster in paternally transmitted cases regardless of the CAG repeat length or age of onset. We conclude that (1) patients lacking the family history of HD frequently show no expansion of the CAG repeats, and (2) the sex of the affected parent influences both the CAG repeat size and the phenotypic expression of the HD gene in the offspring. PMID- 8208413 TI - Suppression of relapsing experimental autoimmune encephalomyelitis in the SJL/J mouse by oral administration of type I interferons. AB - We induced a chronic relapsing form of experimental autoimmune encephalomyelitis in 7- to 10-week-old female SJL/J mice using a subcutaneous injection of an emulsion containing syngeneic mouse spinal cord homogenate in phosphate-buffered saline and Mycobacterium tuberculosis (MT) in incomplete Freund's adjuvant. Following the animals' recovery from the first attack periods, we fed them varying doses of type I interferon (IFN) or mock IFN three times per week for 6 weeks. This treatment decreased proliferation to guinea pig myelin basic protein and MT compared with control in draining lymph node and diminished inflammation in the CNS. Oral IFN altered the cytokine profile of concanavalin A-activated spleen cells by decreasing IFN-gamma secretion. These results suggest that type I IFNs are active by the oral route, have significant clinical and immunomodulatory effects, and can decrease an established and ongoing immune response to sensitized antigens. The oral administration of biologic-response modifiers, such as type I IFNs, provides a potentially nontoxic, convenient, continuous means of delivering immunoactive substances via the gut regional immune system that can alter cytokine production and suppress clinical relapses. PMID- 8208414 TI - Abnormalities in the expression of beta-spectrin in Duchenne muscular dystrophy. AB - We studied beta-spectrin using an immunologic probe in muscle samples from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), other disease controls, and normal controls. By immunohistochemistry in DMD samples, beta-spectrin showed reduced or interrupted staining of the entire cell surface or only patches of bright staining at the cell periphery. There were also alterations of beta-spectrin immunostain in fibers that were not degenerating or regenerating. By immunoblotting, the amount of beta-spectrin in muscle was reduced and varied from 52% to 78% of the normal controls. We found normal values of beta-spectrin in BMD and disease controls. These observations indicate that the expression of beta-spectrin in DMD is abnormal and that beta-spectrin immunolabeling is not a good marker for monitoring membrane integrity in DMD muscle. PMID- 8208415 TI - Prior blood transfusions and Alzheimer's disease. AB - We performed a population-based, case-control study to evaluate prior blood transfusion as a potential risk factor for Alzheimer's disease (AD). All cases were incident cases of AD from 1975 to 1984 with residence for 40 years or more in Olmsted County, Minnesota, prior to their onset of dementia (N = 252). There was one age- and gender-matched control for each case. We ascertained the number of blood transfusions prior to the age of onset of dementia and the corresponding year in each control. Sixty-five cases and 55 controls had at least one prior blood transfusion. We did not find a significantly increased risk of AD for the events of at least one, three, or six blood transfusions. PMID- 8208416 TI - Rapid diagnosis of tuberculous meningitis by a simplified nested amplification protocol. AB - We have developed a simplified protocol based on nested polymerase chain reaction (PCR) for early diagnosis of tuberculous meningitis. Using this protocol, we detected the Mycobacterium tuberculosis genome within 24 hours in the CSF of 19 of 21 patients (90%) with clinically suspected tuberculous meningitis. The PCR results were negative in all 79 nontuberculous meningitis controls. PMID- 8208417 TI - Motor neglect associated with a discrete parietal lesion. AB - The syndrome of motor neglect may follow brain lesions affecting frontal, subcortical, and parietal structures. However, pure motor neglect has not been previously associated with a lesion confined to the parietal lobe. We observed a 79-year-old right-handed man with right-sided limb akinesia and motor neglect without concomitant sensory or visuospatial neglect. MRI showed a left posterior parietal infarct sparing the primary sensorimotor cortex. Transcranial magnetic stimulation showed comparable thresholds for electromyographic activation of the muscles of the right and left arm and normal central motor conduction times, indicating functional integrity of the motor cortex. This case demonstrates that a discrete parietal lesion can produce a pure intentional disorder, independent of sensory or visuospatial neglect. PMID- 8208418 TI - CSF neuron-specific enolase after methohexital activation during electrocorticography. AB - We report changes in CSF and serum neuron-specific enolase (NSE) before and after methohexital infusion during electrocorticography in three patients undergoing epilepsy surgery. NSE is a critical enzyme for energy metabolism that accounts for 1.5% of all soluble brain protein and is an accepted marker of neuronal injury. CSF NSE rose three- to fourfold from baseline within 60 minutes after methohexital activation. Serum NSE was unchanged. This report supports evidence that CSF NSE rises acutely after induction of epileptiform activity and suggests that CSF NSE is a marker of seizure activity. PMID- 8208419 TI - What should a graduating medical student know about neurology? The American Academy of Neurology Undergraduate Education Subcommittee. PMID- 8208420 TI - Research opportunities in dystonia: National Institute of Neurological Disorders and Stroke workshop summary. PMID- 8208421 TI - Cerebral infarction following intravenous immunoglobulin therapy for myasthenia gravis. PMID- 8208422 TI - Clinical significance of hypointensity in the motor cortex on T2-weighted images. PMID- 8208423 TI - Branch retinal arterial occlusion caused by a preretinal arterial loop. PMID- 8208424 TI - Reversal of amphotericin-B-related encephalopathy. PMID- 8208425 TI - Reversal of subacute paraneoplastic cerebellar syndrome with intravenous immunoglobulin. PMID- 8208426 TI - Imaging in motor neuron disease. PMID- 8208427 TI - Parkinson's disease dyskinesias. PMID- 8208428 TI - Parkinson's disease dyskinesias. PMID- 8208429 TI - Pendular pseudonystagmus. PMID- 8208430 TI - Anticoagulation after hemorrhage. PMID- 8208431 TI - Wegener's granulomatosis. PMID- 8208432 TI - Cyclosporine and Duchenne muscular dystrophy. PMID- 8208433 TI - More on tissue transplantation in PD. PMID- 8208434 TI - The myth of carotidynia. PMID- 8208435 TI - Cluster tic syndrome. AB - Cluster tic syndrome (CTS) is a disorder characterized by three types of pain attacks. One resembles trigeminal neuralgia, the second resembles cluster headache, and the third is mixed, starting as a neuralgic pain immediately followed by a homolateral headache accompanied by autonomic signs. This type of attack is pathognomonic for CTS. The three pain types can all be provoked. CTS appears between ages 20 and 70 and may be either episodic or chronic; medical treatment is poor. PMID- 8208436 TI - Bovine spongiform encephalopathy in cattle mimics ultrastructurally experimental scrapie and Creutzfeldt-Jakob disease in rodents. AB - We report a comparison of the ultrastructural pathology of bovine spongiform encephalopathy, experimental scrapie in hamsters and a panencephalopathic model of Creuzfeldt-Jakob disease (CJD) in mice. Vacuoles in dendrites, intramyelinic vacuoles (myelin ballooning), dystrophic axons, phagocytic astrocytes and macrophages, differing in extent, were found in all three models. We conclude, that this axonal and myelin pathology is a phenomenon common to the three models of SSVE studied, and the differences between panencephalophatic CJD and polioencephalopathic BSE and scrapie are only quantitative. PMID- 8208437 TI - Analysis of heavy metals content in the brain with the use of electron paramagnetic resonance in a clinically unusual case of hepato-lenticular degeneration. AB - An analysis of heavy metals content in the brain of a clinically unusual case of hepatolenticular degeneration was performed with the use of paramagnetic resonance. The studies established a manyfold increase of copper content in the brain in the form of free ions, and, less significant, also in the form of copper multi-ion clusters. The content of iron in the studied brain was lower than in controls. These results confirmed significantly the neuropathological diagnosis of hepato-lenticular degeneration. PMID- 8208438 TI - Adrenal medulla grafts into the rat striatum--an evaluation of survival and dynamics of the host brain response. AB - Allogenic adrenal medullary tissue was implanted into the striatum of 68 rats. The material was evaluated by routine histological, histochemical, immunocytochemical as well as histofluorescence techniques 1, 3, 7, 14, 21 and 42 days after implantation. The viability of chromaffin cells continued through the 21st day after the implantation. The host brain tissue responded in two ways. First, by macrophagic resorption of the progressively necrotic graft in the experimental group and of the damaged area along the needle tract, noted both in experimental and control animals. This was accompanied by demarcation by proliferating reactive astrocytes and microglial cells. Second, by lymphocyte infiltration in the graft and around it, detected only in the experimental group which suggested immunological rejection. PMID- 8208439 TI - Verapamil reduces quinolinic acid-induced neuronal damage in rat hippocampus in vitro. AB - The effect of the organic calcium channel blocker, verapamil, on quinolinic acid (QUIN) neurotoxicity in rat hippocampal cultures was studied. Verapamil and QUIN, both in 100 microns concentration, were added simultaneously to the culture medium. Ultrastructural analysis showed that verapamil was able to reduce typical QUIN-induced tissue damages. Especially, 3 and 7 days after exposure to the two agents, majority of both neurons and postsynaptic dendrites revealed normally appearing morphological features. The results support the suggestion of the important role of calcium entry in the development of QUIN neurotoxicity. PMID- 8208440 TI - Rare coexistence of congenital malformations in adult. AB - Coexistence of several developmental abnormalities in adults is very rare and often asymptomatic. In many instances appearance of clinical symptomatology is evoked by some additional factors, not related directly with the basic pathological process. In a 21-year-old oligophrenic man a progressive paresis of inferior limbs appeared in the course of the upper respiratory tract infection. During 5 days of hospitalization transient peripheral paresis of the right facial nerve, tetraplegia, sphincter and respiratory disturbances occurred. Guillain Barre syndrome and subarachnoid hemorrhage were diagnosed. On autopsy hemorrhagic focus in the medulla and in the cervical and upper thoracic parts of the spinal cord was found. Microscopic examination revealed hypocellularity of the 2nd and 4th layers of the temporal cortex, presence of the central canal within the brain stem, and hemorrhagic focus in the medulla. Two malformations in spinal cord were revealed: intraspinal angioma extending from the C2 to the Th6 segments and diastematomyelia within Th11 and lumbar segments. Diastematomyelia, cortical hypocellularity and angioma composed of fetal, lacunar artery- and vein-like vessels, are related with different periods of the ontogenic development. Coexistence of these malformations indicates prolonged action of the pathogenic factor(s), both in the embryonic and fetal life. PMID- 8208441 TI - Morphological changes in the peripheral nervous system in the case of congenital malformations of the spinal cord. AB - A 21-year-old oligophrenic man developed after upper respiratory tract infection, quadriplegia with sphincter and respiratory disturbances. Lumbar punction revealed subarachnoid bleeding and elevated cerebrospinal protein level. Guillain Barre syndrome and subarachnoid hemorrhage were diagnosed. At autopsy intraspinal angioma (C2-D6) and diastematomyelia (D11-lumbar segments) were found. Beside, intraspinal hemorrhage was present. Morphological examination of posterior and anterior spinal roots as well as peripheral nerves was done. Spheroids, axonal degeneration and prominent loss of myelinated fibers were observed in the proximal parts of the spinal roots. Axonal degeneration of myelinated fibers and regenerated fibers were noted in the distal parts of spinal roots and in peripheral nerves. Abnormal, fetal-like vessels were present in the spinal roots. Two mechanisms of acute and chronic changes (transneuronal and Wallerian degeneration) are discussed. PMID- 8208442 TI - Paraneoplastic subacute sensory neuronopathy. Clinical-pathological study. AB - We report 2 cases of subacute sensory neuropathy (SSN) in small cell cancer of the lung. In both cases motor disturbances were caused by motor neuropathy and neuropathy as well. In both cases we observed altered immunoreactivity of the nervous tissue, suggesting the participation of humoral immunity in the tissue damage. PMID- 8208443 TI - Intravascular coagulation in the central nervous system in patients with acute myeloblastic leukemias. AB - The frequency and distribution of intravascular coagulation (IVC) were studied in brains of 121 patients who had died due to acute myeloblastic leukemias type M1 or M2. The IVC within the brain was observed in 59% of cases, more frequently in patients treated with polychemotherapy, especially according to TAD or VAPA protocols. The microthrombi were found predominantly in capillaries and small venous vessels. IVC was more frequent in cerebral and cerebellar white matter and in the neighbourhood of lateral ventricles (hippocampus, thalamus). In patients who had developed brain hemorrhage in the course of primary neoplasmic disease IVC was very frequent phenomenon, thus IVC is considered to be an important factor in the development of CNS hemorrhages in myeloblastic leukemias, irrespective of thrombocytopenia related to bone marrow involvement. PMID- 8208444 TI - Effect of clinical death on inositol 1,4,5-trisphosphate in the rat brain. AB - Changes of inositol 1,4,5-trisphosphate content in the rat brain have been evaluated by means of the radioimmunologic method during 5-min clinical death and up to 2 hrs after resuscitation. Ischemia produced a decrease of IP3 content in the brain on the average to 63% of the control values. IP3 concentration in the brain increased on the average to 197% of the control values at the 15th min after resuscitation, and decreased to 127% at the 60 min. Two hours after resuscitation the IP3 content in the brain again increased on the average to 187%. The new data on brain metabolism in the ischemic conditions and the role of IP3 as the second messenger and mediator of neuromodulation processes are discussed. PMID- 8208445 TI - Cerebral infarcts in newborns and infants with cyanotic cardiac anomalies. AB - Neuropathological examination of six brains of newborns and infants who died in the course of congenital cyanotic cardiac anomalies showed focal brain lesions. The material included five cases from two weeks to two months of age, and one two year-old infant. In two of them, the periventricular ischemic infarcts were found, in one multifocal encephalomalacia due to multiple vascular occlusions, and in three the necrotic foci corresponded to the supply of large cerebral arteries. The character and topography of severe brain lesions, particularly within the hemispheric white matter, were clearly influenced by the immaturity of the cerebral structures. PMID- 8208446 TI - [An anesthetized anesthesiologist tells his experience of waking up accidentally during the operation]. AB - We report the recollections of an anaesthesiologist who experienced urogenital surgery under balanced anaesthesia which was insufficient to prevent awareness during a part of the procedure. The patient was hard apprehensive before surgery and neither sedative nor amnesic drugs were done as premedication. He received an Innovar, thiopentone, suxamethonium, nitrous oxide/oxygen sequence for intubation. Awareness occurred not long after but before administration of isoflurane for maintenance. In that terrifying moments the patient was conscious without pain. According to him the worst aspect of the experience was desperately wanting to move or speak and being unable to do so. In the event of unexpected awareness, the anaesthesiologist must deal with the patient in an honest and forthright manner. Failure to do so lead to dire psychological consequences for the patient and expensive malpractice litigation for the anaesthesiologist. PMID- 8208447 TI - [Transesophageal echocardiography in resuscitation. Indications and presentation of various clinical cases]. AB - The diagnostic potential of Transesophageal Echocardiography (TEE) is well established in patients with suspicion for some life-threatening diseases as cardiogenic cerebral embolization, aortic dissection, intracardiac or thoracic masses, acute valvular dysfunction or sepsis of undetermined origin, which represent a relevant part in the activity of Intensive Care Units (ICU). Thus, an increasing role of TEE may be foreseen in this arena, also due to some of the known odds of ultrasound techniques compared to other imaging tools like CT scan or MRI (lower cost and beside availability). The aim of the present paper is to briefly review the main indications for TEE in ICU, and to report on some illustrative cases from our experience of I year in this field. Twenty-eight seriously-ill patients referred to our ICU between December 1991 and December 1992 were investigated for 1 of the following diagnostic problems: a) chest trauma with suspicion for aortic dissection and/or mediastinal bleeding; b) sepsis of undetermined origin; c) cerebral transient ischemic attack or stroke; d) assessment of cardiac function in potential heart donors. TEE was performed by means of commercially available instruments (either Hp Sonos 1500 or Esaote Sim 7000 Color Flow Mapping), with conventional monoplane probe or so-called wide angle, "panoramic" probe, respectively. In most of the patients studied, TEE provided either unique or complementary, diagnostically useful, information. By panoramic approach, which yields imaging field up to 270 degrees, a comprehensive visualization of the heart, aorta and mediastinal structures was possible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208448 TI - [Hypotension controlled with ATP in orthopedic surgery: incidence of atrio ventricular conduction disorders]. AB - Adenosine triphosphate (ATP) has been effectively used for induced hypotension in man. Atrio-Ventricular (A-V) conduction disturbances have been observed after adenosine bolus injection and during continuous ATP i.v. infusion. The present perspective investigation was designed to determine the incidence of A-V conduction disturbances during ATP-induced hypotension. Thirty-five normotensive healthy patients (ASA I-II) with no preoperative therapy were subjected to the same anesthetic technique for orthopedic surgery. Premedication consisted of diazepam and atropine. Anesthesia was induced with thiopental and fentanyl followed by atracurium for intubation. The maintenance anesthesia consisted of isoflurane (1.5% inspired)-N2O (60%) in oxygen and incremental doses of fentanyl; the lungs were mechanically ventilated. Dipyridamole (0.15 mg kg-1) was given 15 min prior to ATP-infusion. ATP was administered by an infusion pump at a dosage of 0.025-0.05 mg kg-1 min-1. The ECG was recorded with a Mingograph 34 tape recorder using 3 pregelled electrodes positioned to give an effective V6 lead pattern. MAP was reduced by 25% and HR increased by 6%. The mean duration of ATP induced hypotension was 75 min +/- 50 and the mean dose of ATP infused was 200 mg +/- 161. Six patients (17%) showed A-V conduction disturbances. There was a I A-V Block (AVB) in 2 cases, a II AVB in 2 cases and a III AVB in 2 cases. In every case the arrhythmia disappeared spontaneously or after ATP-infusion suspension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208449 TI - [Hemodynamic and oxygen transport effects of dobutamine in critically ill patients]. AB - The study evaluates the cardiocirculatory and oxymetric effects of dobutamine infusion in doses between 5 and 15 g/kg/min for a period of 48 hours in 18 critical patients of whom 9 with a low cardiac index (mean 2.1) and 9 with a normal or increased cardiac index (mean 3.3). The beta mimetic effect of the drug is particularly evident in the 9 hypodynamic patients who benefited from a 28% increase in the cardiac index. Likewise, oxygen transport and consumption improved by 22% and 15% respectively. In overall terms, the variables which revealed significant modifications were: cardiac index (CI), systolic index (SI), mean pulmonary pressure (MPAP), pulmonary impaction pressure (PAWP), systemic and pulmonary vascular resistance (SVRO), PVRI), oxygen transport and consumption (DO2, VO2) (No major changes were observed in mean arterial pressure (MAP) and heart rate (HR). No tachyphylaxia was noted after 48 hours of continuous infusion. PMID- 8208450 TI - [Automatic fluid control during high-flow continuous hemofiltration: the Equaline system]. AB - OBJECTIVE: To describe the use of an automatic fluid control system, Equaline, during high flux continuous hemofiltration. DESIGN: Prospective descriptive study. SETTING: General intensive care unit in a general hospital. PATIENTS: 15 consecutive patients suffering from septic shock, hypercatabolic with acute renal failure. INTERVENTION: Pump driven continuous veno-venous hemofiltration (PDCVVH) with high flux was performed. All pts were intubated, under mechanical ventilation and treated with vasoactive agents for hemodynamic instability. Fluid balance was achieved with an automatic fluid control system, Equaline, on daily basis according to clinical needs. MEASURES: Length of treatment, daily amount of ultrafiltrate and urea removal, urea and creatinine blood level before and after the treatment were registered. RESULTS: Age was 59.1 years, SAPS 17.2. Patients were treated for an average period of 9 days obtaining a daily ultrafiltrate production of 21.4 L. In all pts, though the high catabolism (daily nitrogen production > 30 g), there was a significant decrease of urea and creatinine concentration. CONCLUSION: Equaline system was able to maintain intravascular volume in the face of high ultrafiltration rate avoiding clinically important discrepancies between ultrafiltrate formation and fluid replacement. We conclude that PDCVVH management is greatly improved with use of such servo-controlled feedback system. PMID- 8208451 TI - [Topical laryngo-tracheal anesthesia and intraocular pressure in anesthesia for ophthalmic surgery]. AB - OBJECTIVE: The reflex response to orotracheal intubation provokes an increase of arterial pressure accompanied by an increase of chorioides volume and a consequent ocular hypertone. There are several methods to reduce the reflex response due to intubation. One of the most effective is topical anaesthesia of larynx and trachea. Experiments were directed to evaluate the efficacy of topical anaesthesia to reduce the intraocular hypertone due to orotracheal intubation. DESIGN: A prospective randomized mask study was conduct on patients undergoing ophthalmologic (anterior segment) surgery at the Eye Clinic of Florence University. METHODS: Intraocular pressure was measured by a Goldman tonometer at four times: T0 = basal, T1 = 2' minutes after induction of general anaesthesia, T2 = 2' minutes after laryngoscopy, T3 = 2' minutes after orotracheal intubation. At the same moments, systolic blood pressure, heart rate, rate pressure pro duct were measured. Patients were randomly divided in two groups: Group L (n = 10) in which was evaluated the efficacy of laryngotracheal topical spray of lidocaine 4% (2 ml) and Group F (n = 10) in which saline was used instead of anesthetic. The filling of the LTA kit (Abbott) was made by a person not involved in the experiments. DATA ANALYSIS: Student's t test for unpaired data. RESULTS: Topical anaesthesia reduces the increase of intraocular pressure, hypertension and rate pressure product due to intubation. The intraocular pressure reduces to 13% less than basal value in Group L and increase to 50% more than basal value in Group F. CONCLUSION: The topical anaesthesia of larynx and trachea is effective to reduce the intraocular hypertension due to the reflex response evoked by orotracheal intubation. PMID- 8208452 TI - [Peridural administration of low-dose morphine on demand following major abdominal surgery]. AB - The present report deals with 20 patients undergoing major abdominal surgery, in whom a postoperative antalgic regimen has been administered on demand by means of morphine via lumbar peridural catheter. We injected 3 mg as the first dose after surgery and subsequent 2 mg doses when required. In each patient we controlled regularly for 72 hours the following: respiratory function, antalgic effects and side effects. We concluded that this technique is fit to obtain good analgesia with rare and mild side-effects. PMID- 8208453 TI - [Two cases of accidental hypothermia]. AB - We report two cases of accidental and moderate hypothermia in drug/addict subjects who came to our attention in coma, shock and respiratory distress, metabolic acidosis and characteristic ECG alterations. We used the methods of minimal invasivity to rewarm them, with good results. The two cases had a different clinical course: the first one presented some important cardiac and respiratory problems, that required 30 days of permanence in our ICU, while the second one had a quick resolution. We believe that the critical time for arrhythmias goes beyond the hypothermic period. PMID- 8208454 TI - [Cerebral venous thrombosis. Report of a clinical case]. AB - A typical case of CVT is reported in which a certain diagnosis was reached only through NMR. Etiopathogenesis, clinical pictures and therapy are shortly discussed. Anticoagulant therapy at both short and long term is a preventive measure recommended for patients with thrombophilia. PMID- 8208455 TI - [Intraoperative fluid administration and severity of the clinical condition]. AB - Fluid overload has been recently suggested to influence morbidity. The aim of this study was to investigate the relationship between the amount of fluid given in the operative room and the severity of illness, which is known to be different in scheduled and emergency surgery. We prospectively studied 78 surgical patients consecutively admitted to our Intensive Care Unit (ICU). We collected the following information: age and weight of the patient, amount of crystalloids, colloids and blood given in the operative room, length of the surgical procedure, SAPS, APACHE II, serum albumin, IUC length of stay, ICU and hospital mortality rate. The anaesthetist, who was responsible for the clinical decision in the operative room, was unaware of the study. The patients were divided in two groups: ELE, 59 patients admitted to ICU after scheduled surgery, and URG, 19 patients admitted after emergency surgery. Age, weight, number of patients operated on abdomen, length of surgical procedure were similar in both groups, but also the amount of fluid given in the operative room were the same (crystalloids 10.1 +/- 4.3 ml/kg/h in ELE vs 10.7 +/- 3.9 ml/kg/h in URG and total amount of fluid 12.1 +/- 5.5 ml/kg/h in ELE vs 14.5 +/- 5.7 ml/kg/h in URG).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208456 TI - [An infrequent case of attempted suicide with colchicine]. AB - The author reports an unusual case of voluntary poisoning caused by 60 mg of colchicine. He describes the physiopathological mechanism of poisoning, the clinical evolution and the treatment. In particular, he examines the ARDS, typical complication, analyzing the responsible mechanism of this event and some of its peculiarities. The author pays particular attention to the blood monitoring levels of HHb as a precious diagnostic index of diffuse infiltrative lung disease. PMID- 8208457 TI - [Emergency diagnostic imaging in thoracic trauma. A clinical case]. AB - The authors report a case of thoracic trauma with pulmonary contusion in which chest X-ray was not significant, nevertheless severe clinical state. They underline the importance of CT in the early evaluation of pulmonary lesions and in their development. PMID- 8208458 TI - [Barrett esophagus. The diagnostic and therapeutic aspects]. AB - The authors, after a dissertation on the aetiopathogenesis of "Barrett's oesophagus", dwell on the precancerous nature of this pathology involving the oesophageal-gastric junction. Its frequent association with cancer explains the necessity for an accurate follow-up in these patients: many investigations can be useful, the radiological study of oesophagus and stomach, manometry, pH-metry, but an irrefutable diagnosis can only be achieved through endoscopy, which makes possible a histological examination of the bioptic fragments. The authors also deal with the ideal therapeutic strategy and differentiate the cases in which the pharmacological therapy is more appropriate from those that need a surgical approach. PMID- 8208459 TI - [The surgical procedure in a case of accidental lesion due to impalement]. AB - The authors describe a case of intraperitoneal anorectal injury. Such injuries now have an improved survival rate as a result undoubtedly of superior resuscitation, early operative management and early use of antibiotics. Civilian life rectal wounds are usually of the penetrating type. Major complications, both of intra and extraperitoneal injuries, are related to infection. The surgical management of these lesions is primarily a proximal diversion of the fecal stream. This is accomplished by a divided--end colostomy. Local wound care must be given for the inevitable infected foreign tract. When sepsis occurs, the surgeon must be prepared to handle it adequately by appropriate incision and drainage. PMID- 8208460 TI - [Splenic rupture in chronic pancreatitis. A clinical case. Observations]. AB - The paper reports a case of splenic rupture during the course of chronic pancreatitis, an event rarely reported in the literature. The anatomical arrangement of organs and peripancreatic vessels is a predisposing factor for this complication. There are essentially three different but correlated pathogenetic hypotheses. The first refers to thrombosis of the splenic vein with portal hypertension documented by some researchers even in angiographical terms: during the course of chronic pancreatitis the spleen is sometimes palpable. Thrombosis and/or vascular compression make the spleen more fragile and its rupture more likely: this is particularly true during the course of calcific chronic pancreatitis and cases involving the tail. An enzymatic factor may also be responsible and this appears more clearly in pancreatitis with pseudocysts. In this case it is the direct action of pancreatic enzymes on the ileum or splenic parenchyma, which may also affect all organs surrounding the pancreas, which leads to hemorrhage or hematoma. Sometimes the cause of bleeding is a pseudoaneurysm of the splenic artery which is eroded by the contents of the pseudocysts themselves. There is also a mechanical hypothesis which some authors consider the sole possibility: in chronic pancreatitis the splenic compartment presents severe perisplenitis which fixes the spleen making it more vulnerable and even a mini-trauma will cause rupture. The patient is almost always an emaciated young alcoholic suffering from chronic pancreatic pathology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208461 TI - [Pelvic actinomycosis in IUD wearers. A case report]. AB - The author describes a case of pelvic actinomyces in woman using intrauterine contraceptive device, in support of frequent association on two conditions. The woman was treated by surgery. Moreover, the author underlines the difficulty in diagnosis, which explains the frequent recourse to surgery. PMID- 8208462 TI - [Infected pseudoaneurysms of the upper limb. A case re-evaluation]. AB - The authors report a case of infected pseudoaneurysm of the brachial artery in a drug addict, treated with aneurysm excision and brachio-brachial bypass with inverted saphenous vein. They review the literature on the subject and management options. PMID- 8208463 TI - [The quality of life of the elderly after a surgical intervention. II. Gastric carcinoma]. AB - Having reviewed the literature on this topic, the authors examined the "quality of life" of elderly patients undergoing surgery for gastric carcinoma over the past 5 years. From the results obtained it was seen that the most frequent operation was total gastrectomy (51.1%), followed by gastric resection (48.9%); it was therefore possible to assert that living patients were all well, with a score of 100 on Karnofsky's scale (22.40%), despite the high percentage of deaths during the period examined. The authors therefore concluded that, given that the "quality of life" of those undergoing surgery was satisfactory, it is worthwhile operating whenever possible to give geriatric patients the possibility of leading a normal life. PMID- 8208464 TI - [Total gastrectomy: a comparison between manual and mechanical sutures]. AB - The authors report their experience of the use of mechanical staplers in total gastrectomy. The advantages of their use can above all be seen in anastomosis, in particular in high-risk areas like esophago-jejunal anastomosis, in which there is a lower incidence of dehiscence and mortality than when manual suturing techniques are used. PMID- 8208465 TI - [Our technic for continent perineal colostomies after the abdominal-perineal amputation of the rectum]. AB - Having briefly outlined the complex question of definitive abdominal colostomy, understood as an inevitable stage in demolitive anorectal surgery if the tumour is localised approximately 7-10 cm from the anus, the authors propose abdominal perineal and perineal colostomy as logical alternative capable of offering a more satisfactory quality of life with equal oncological radicality. Currently used techniques are then discussed by which the perineal colostomy is fitted with a sphincter to make it continent. From this it emerges that the common limits to each method largely consist in the complexity of the operation and the type of postoperative care required, including a long period of postoperative stomal rehabilitation (with the relative equipment and staff) in order to achieve better functional results. Using their 10-year experience of perineal colostomies, also with sphincters, as a starting point, the authors illustrate their personal technique which ensures a degree of stomal continence which is comparable if not better than that obtained using other surgical procedures but is not so difficult to perform and does not require such full-time assistance. The consequent improved risk-benefit ratio for this type of operation means that the indications can be widened to coincide with those for traditional abdomino-perineal colostomy both with regard to age and the stage of disease. There are two basic steps in this technique. The first involves abdomino-peroneal demolition secondary to cancer and follows the conventional lines of classic abdomino-perineal colostomy; the second involves the sphincteric reconstruction which is performed using an extremely simple technique. The two small anti-mesenteric tenia of the prestomal colon are mobilised and placed around the colon so that they form a smooth double sphincter which completely occludes the former's lumen. On completing surgery, the sphincteric structure lies just above the perineal stoma whereas the underlying tract of colon, which is the site of the muscle graft, is completely extra-corporal until it has become regularized. The surgical safety of this technique is immediately evident from the fact that since it was introduced temporary abdominal colostomy has been no longer been performed, thus avoiding subsequent colorrhaphic surgery and reducing hospital stay, patient suffering and social costs. PMID- 8208466 TI - [Recurrent neoplasms of the rectum: their CT diagnosis]. PMID- 8208468 TI - [Antibiotic prophylaxis with cefoxitin in acute nonperforated appendicitis]. AB - The purpose of this investigation was to examine the safety and efficacy of cefoxitin in preoperative prophylaxis of acute nonperforated, appendicitis. During twelve consecutive months, a single i.v. dose of cefoxitin was administered to 151 patients suffering from nonperforated appendicitis. The study confirms the preoperative prophylaxis with cefoxitin used regularly with patients who are undergoing an appendicectomy. PMID- 8208467 TI - [The usefulness of thyroxine treatment after subtotal thyroidectomy for endemic goiter]. AB - The aim of the present study was to assess the appropriateness and value of prophylactic thyroxine therapy in the treatment of postoperative complications (relapse, postoperative hypothyroidism) following subtotal thyroidectomy for endemic goiter. The study was carried out in a group of 139 patients undergoing subtotal thyroidectomy for endemic goiter between 1978 and 1987. Clinical follow up included hematochemical and scintigraphic analyses. Patients were divided into two groups. The first group included 74 patients who received postoperative hormone replacement therapy. The second group of 65 patients did not receive any treatment. results show that hormone replacement therapy is unnecessary in most cases since the majority of patients require euthyroid values a few months after operation. Thyroxine therapy was indicated, however, in cases of clinically evident postoperative hypothyroidism which persisted during follow-up. PMID- 8208469 TI - [Perioperative teicoplanin prophylaxis in patients undergoing breast reconstruction with the abdominal wall. A case-control study]. AB - The authors report the results of a randomized clinical trial of antibiotic prophylaxis of postoperative infection following breast reconstruction by transposition of rectus abdominis myocutaneous flap (TRAMF). The aim was to evaluate the efficacy and tolerability of a short-term parenteral prophylaxis with Teicoplanin and the end-point of the study was the evaluation of wound contamination assessed by means of microbiologic culture of drainage fluid. From October 1990 to March 1992 38 patients were recruited: 20 patients in the antibiotic prophylaxis arm and 18 patients in the control group. Analysis of drainage fluids showed a higher contamination rate (15/18 = 83%) in the control group as compared to the prophylaxis arm (2/20 = 10%) (p < 0.0001). Moreover, 11 patients in the control arm suffered from fever > 37.5 degrees C for at least 3 days as compared to 1 patient in the antibiotic prophylaxis group; the postoperative stay was 13.3 +/- 4.3 and 9.0 +/- 1.6 in the control and antibiotic arm respectively. No antibiotic related side effects were evidenced through the study. These results seem to confirm the value of parenteral short-term antibiotic prophylaxis of postoperative infection in such kind of "clean" operative procedure. PMID- 8208470 TI - [An experimental study of a new ultrasonic scalpel. Observations on the quality of the ultrasonic effect and the prospects for its clinical use on different parenchyma and tissues]. AB - The ultrasonic scalpel has been used for some time in surgery in tissue with a predominantly cellular component since it can be used selectively on the parenchymatous component while respecting the vasculo-stromal component. On the basis of their earlier experience and using a versatile ultrasonic device currently utilised in plastic surgery, the authors subjected a series of animal organs to ultrasonic action at a frequency of 19800 Hz and with an output of 65 Watt. The aim of the study was to evaluate the widest potential in terms of efficiency and safety for the use of a ultrasonic scalpel on a vast range of animal parenchyma (batches of Sprague-Dawley rats). The authors' comments and histological results highlight the striking efficiency of this form of energy in the dissolution of parenchyma while respecting the organ's vascular and stromal components. PMID- 8208471 TI - [The effect of the degree of lymphocytic infiltration on the long-term survival of patients undergoing surgery for the exeresis of gastric cancer]. AB - The predictive value of tumor lymphocytic infiltration was studied in 186 gastric cancer patients curatively resected. All patients were followed-up for over 10 years. LI was negatively correlated with p-TN stage of disease. A poorer prognosis was detected in patients with minor or no tumor lymphocytic infiltration. LI was an independent prognostic parameter according to the Cox model and logistic regression analysis. These findings suggest that LI should also have been considered in the current staging of gastric cancer. PMID- 8208472 TI - [Ultrasonic lipoemulsification: a working definition and ex-vivo study on human adipose tissue]. AB - On the basis of previous reports by other authors which have become increasingly numerous over the past years, we have focused our attention on the use of ultrasonic energy in the medical field to resolve medical and cosmetic problems, such as lipodystrophy and diffuse subcutaneous adiposity. In order to standardise the dissolution times of human subcutaneous adipose tissue we used a ultrasonic generator operating at a constant frequency of 19800 Hz, but which was able to emit a range of power from 0 to 100 Watt. The ultrasounds were applied (according to a scale of power) using a titanium probe to fat samples with a volume of 1 cm until each sample had fully dissolved. This allowed the levels of greatest working efficiency to be established for the most commonly used probes. PMID- 8208473 TI - [Inguinal hernia containing bladder and ureter. A clinical case]. AB - The authors describe an uncommon case of inguinal hernia with bladder and ureter content. Bladder herniation preoperative diagnosis has been achieved by means of clinical history, objective and instrumental examination (cystography). As usually happens, ureteral herniation was a chance finding; this could involve a trick in surgery setting up and doubts in the treatment methods. PMID- 8208474 TI - [Carcinoma of the large intestine following ureterosigmoidostomy in a patient with bladder exstrophy]. AB - The paper reports a case of intestinal occlusion due to adenocarcinoma of the large intestine as a sequel to ureterosigmoidostomy for exstrophy of the bladder which was subsequently converted to ureteroileocutaneostomy. Inadequate follow-up did not allow an early diagnosis to be made. The authors underline the need for annual colonoscopy in all patients suffering from or with previous ureterosigmoidostomy given the high incidence of malignant transformation of the colon. PMID- 8208475 TI - [Lipoma of the colon. Its clinical significance and treatment]. AB - The authors present the observation of a case of lipoma of the transverse colon. They review the latest literature confirming the rarity of this case and its clinical importance for diagnostic and therapeutic problems that it could give. PMID- 8208476 TI - [An anatomicoclinical case of lipoma of the sigmoid]. AB - The authors describe a case of a submucosal lipoma of the large intestine. Family, physiological, and remote anamnesis of the patient was negative to inflammatory or neoplastic intestinal diseases. The symptomatology was not characteristic like the several cases reported in the literature, by abdominal cramps, subocclusion or total occlusion crisis and rectal bleeding. The patient presented with a symptomatology characterized by altered bowel habit, and evacuations of blood-stained feces. The clinical diagnosis was difficult for the aspecific symptoms referred. A barium enema and colonoscopy examination showed a suspected benign neoformation localized within the sigmoid colon. The patient underwent surgery and the following histologic exam exhibited a submucosal lipoma with an atrophied superficial epithelium replaced by necrotic and granular tissue, marked architectural disarray of glandular crypts and intensive inflammatory infiltrate of tunica mucosa. PMID- 8208477 TI - [Invagination of the small intestine due to leiomyoma. A case report of echographic diagnosis]. AB - The authors describe a case of intestinal invagination caused by leiomyoma of the small intestine. They make the diagnostic difficulties of the disease apparent and stress the importance of abdominal echography in cases of acute abdominal disorders. PMID- 8208478 TI - [Congenital diverticulum of the small intestine: Meckel's diverticulum or intestinal duplication?]. AB - A congenital diverticulum of the small intestine is a condition with only a low morbidity and is generally a Meckel's diverticulum. There is, however, another congenital malformation, which can closely resemble a Meckel's diverticulum, but has another etiology, the tubular duplication of the small intestine. The authors point out the embryologic, anatomic and histological findings between these different but very similar malformations. It seems that the diagnosis of duplication is not often considered when finding a diverticulum of the small intestine and such a malformation is too easily called a Meckel's diverticulum. PMID- 8208479 TI - Waiting lists for coronary artery surgery: can they be better organised? AB - AIM: To determine whether a numerical ranking system can provide an equitable basis for prioritising patients awaiting coronary artery bypass grafting. METHODS: A review of the current coronary surgery waiting list was undertaken using a newly developed scoring system. The factors included in the score were age, symptoms, results of exercise testing, coronary anatomy, employment status and perceived surgical risk. This score was compared with a Canadian consensus system. Rankings were then compared with the clinical priorities given by clinicians when the patients were placed on the waiting list. RESULTS: There was excellent correlation between the two priority ranking systems using only those items included in the Canadian system (r = 0.9179). However, correlation between the Canadian system and the full Green Lane Hospital (GLH) scoring system was weaker (r = 0.6869). The Canadian system assigned higher surgical priorities than Auckland clinicians. Comparison between the GLH system and clinical priority gradings (O, urgent out of hospital), (A) and (B) showed considerable scatter. Waiting times for these three categories considered acceptable by the Canadian consensus group were two to six weeks for priority (O), six weeks to three months for priority (A) and three to six months for priority (B). The mean times on the waiting list for the 260 patients still awaiting surgery at GLH were two months for (O), 11 months for (A) and 22 months for (B). CONCLUSIONS: The Canadian and expanded GLH ranking systems are no more than aids to establishing priorities. They cannot replace clinical judgement because the importance of individual scoring items is heavily influenced by the ranking of other items. Waiting times for surgery are now grossly excessive despite the use of criteria for entry to the waiting list which are very conservative by international standards. There is no equitable or clinically acceptable way to modify priorities to reduce waiting times, and institution of a booking system is impractical. PMID- 8208480 TI - Medical and scientific fraud. PMID- 8208481 TI - Identification of human immunodeficiency virus type 2 in a New Zealand resident. AB - AIMS: To determine the human immunodeficiency virus (HIV) types infecting a West African immigrant to New Zealand. To develop an HIV type 2 specific polymerase chain reaction (PCR). METHODS: The HIV antibody status of the patient was determined using both HIV-1 and dual HIV-1 and 2 enzyme immuno assays (EIA). Western blot with HIV-2 and HIV-1 and 2 strips was used as a confirmatory assay. DNA from white blood cells was extracted and HIV proviral DNA amplified using either primers specific to the HIV-2 gag region (VB305 and VB312) or to HIV-1 gag (SK38/39) and env (SK68/69) regions. Amplified products were electrophoretically resolved, southern blotted and probed with specific oligonucleotide probes. RESULTS: The patient serum was strongly reactive for HIV antibodies by EIA and showed multiple reactivity when tested by western blot against both HIV-1 and HIV 2 proteins. DNA was only amplified with primers specific to HIV-2 and the 298 bp product hybridized with an HIV-2 specific probe. No HIV-1 DNA was amplified from the patient. CONCLUSION: This individual is infected with HIV-2 and has most likely developed antibodies that cross-react with HIV-1. We believe this is the first report of an HIV-2 infected individual in New Zealand. PMID- 8208482 TI - Prevalence of known diabetes in a multiethnic community. AB - AIMS: To describe the prevalence of known diabetes in an area of New Zealand with a large Pacific Islands and Maori population. METHOD: A cross sectional door to door census with identification of those with known diabetes was conducted between April and October 1992. The data was validated by comparison with available local general practice diabetes registers and data from a repeat visit to a randomly selected 5% of houses. RESULTS: Interviews were completed at 92.7% of the 5081 households, containing 22,651 residents (1417 European, 5606 Maori, 14,802 Pacific Islands). The Pacific Islands population was 40% larger than that predicted from the 1991 census. The age adjusted prevalence of known diabetes in adults (aged > or = 20 years) was 2.8% (95% CI 1.9-3.9) in Europeans, 6.9% (95% CI 6.0-7.9) in Maori and 4.6% (95% CI 4.1-5.1) in Pacific Islands people. The greatest differences in prevalence were found in those aged 40-59 years. Interviews at 185/280 houses revisited showed that 13% of households had moved completely in the 2-8 months between visits. Comparison between participating general practice registers and the door to door survey database showed that 11.2% (26/232) of diabetic individuals were missed by the door to door survey, and 23.7% (55/232) were not on the register of the named general practitioner. CONCLUSIONS: The prevalence of known diabetes in the community is much higher than that in the workforce. Differences between Maori and Pacific Islands people may be due to more undiagnosed diabetes or a lower risk of diabetes in the latter. PMID- 8208483 TI - Injury surveillance in public hospital emergency departments. AB - AIMS: To identify existing surveillance initiatives and to seek and reach consensus on a national minimum data set for injury surveillance in public hospital emergency departments in New Zealand. METHODS: Every public hospital emergency department was visited to obtain information on current surveillance initiatives. At the same time, guidelines for a national minimum data set for injury surveillance were considered. National organisations who might use the information were contacted and also asked to consider the guidelines. RESULTS: Of the 43 public hospital emergency departments visited, five had on-site computerised information systems, the majority collecting data manually. Basic demographic data and information in a narrative form were the only data recorded consistently by all hospitals. A national minimum data set for injury surveillance was adopted by general agreement at a consensus forum, held in Wellington, in March, 1992. Current developments indicate that the minimum data set for injury surveillance, as adopted at the forum will become a component of the National Minimum Data Set within the proposed Health Information Strategy for New Zealand. CONCLUSIONS: Injury data collection will, in time become mandatory. However, the promotion of the minimum data set for injury surveillance by health professionals, national organisations and community groups will be essential to ensure its implementation and utilisation for the prevention and control of injuries. PMID- 8208484 TI - Aspects of central venous access catheter usage in patients with malignancy. AB - AIMS: A review of 5 years' experience with central venous access catheters (CVAC) to examine the results of catheter placement technique (open or percutaneous) on subsequent CVAC performance. In addition the catheter function and utilisation of both Hickman type and Access Port type of CVAC were reviewed to assess the indications and the types of access devices chosen in selected patients. METHODS: A retrospective review of CVAC between 1987 and 1991 was undertaken. During this time 113 CVAC were placed by the open (n = 76) or percutaneous (n = 37) method. The type of catheter used was Hickman (n = 79) or Access Port (n = 34). Indications for CVAC placement were haematological malignancy 74.2%, other malignancy 14.1%, and the rest were accounted for by TPN, HIV infection, osteomyelitis, anaemia and haemochromatosis. RESULTS: There was no difference between duration of function for CVAC placed by the open (5.1 months 95% CI, 3.8 6.4) and percutaneous methods (3 months, 95% CI 2.2-3.8). Nor was there a difference in duration of function between Hickmans (4.47 months, 95% CI 3.3-5.6) and Access Ports (4.3 months, 95% CI 2.8-5.8). CVAC morbidity included sepsis, accidental displacement, major venous thrombosis, bleeding and port erosion. There was no significant statistical difference in the incidence of complications between the open (25%) versus percutaneous (22%) techniques. The clinically significant difference in morbidity related to the type of catheter used: Hickman (18%) versus Access Port (35%). Infection and sepsis were a problem in the Port group accounting for 20.6% of the complications. CONCLUSIONS: We believe CVAC account for significant morbidity which is not often taken into account by those recommending their use, particularly in the management of malignant disease. In addition CVAC placement should be part of a service in consultation. There are cost-benefit advantages in using orthodox central lines in the sick patient with a view to placing a CVAC at a later date. PMID- 8208485 TI - A rod for whose back? PMID- 8208486 TI - Management of cornual pregnancy with oral methotrexate. PMID- 8208487 TI - Drug-resistant Plasmodium vivax malaria. PMID- 8208488 TI - Death following allopurinol hypersensitivity syndrome. PMID- 8208489 TI - Sudden sensorineural hearing loss. PMID- 8208490 TI - DPT vaccine and neurological dysfunction. PMID- 8208492 TI - Haemophilus influenzae b vaccine. PMID- 8208491 TI - Mammography screening under the age of 50. PMID- 8208493 TI - Thyroid hormone in a health food capsule. PMID- 8208494 TI - Respiratory distress syndrome in New Zealand: evidence from the OSIRIS trial of exogenous surfactant (Exosurf). AB - AIMS: To assess the impact, mortality, morbidity and economic costs, of respiratory distress syndrome severe enough to warrant ventilation in one year in New Zealand. METHODS: Review of data from all five New Zealand regional neonatal intensive care units' participation in the international OSIRIS trial of exogenous surfactant (Exosurf) treatment for respiratory distress syndrome (involving 6700 infants in 21 countries), and extrapolation of these data to a full year. RESULTS: There were 265 New Zealand infants entered in the OSIRIS trial; the mean birthweight was 1335 g and mean gestation 29 weeks; 61% of infants were less than 30 weeks gestation. Forty-seven infants (17.7%) died prior to discharge from hospital, 40 deaths being attributed to prematurity or respiratory distress syndrome. One hundred and two infants (38.5% of the cohort; 45% of surviving infants) were oxygen dependent and 36 infants (13.6%) were dead at 28 days of age. Thirty-four infants (12.8% of the cohort; 15% of surviving infants) were oxygen dependent and 40 infants (15%) were dead at the expected date of delivery. Infants were intubated for a mean 12.5 days, with surviving infants of less than 27 weeks gestation intubated for a disproportionately long period of time. Seventy-two infants (29% of the 246 infants examined) had an abnormality detected by cranial ultrasound scan at 1 or 6 weeks of age and in 23 (9%) this was a major abnormality. Of surviving infants 16 (7.5% of 213 examined) had a major abnormality on cranial ultrasound scan. Amongst infants at high risk for respiratory distress syndrome (gestation less than 30 weeks) 53% received antenatal steroids, compared with 22% in the OSIRIS trial overall. In a full year the cost of caring for infants with respiratory distress syndrome sufficiently severe enough to warrant ventilation is estimated to be NZ$12.5 million. The average cost of caring for a surviving infant was roughly NZ$52,500 and a nonsurviving infant was NZ$24,500. CONCLUSIONS: In a full year (total births 60,000) approximately 350 New Zealand infants may require ventilation for respiratory distress syndrome. Increasing the percentage of infants who receive antenatal steroids is likely to be extremely cost effective. In the era of antenatal steroids and exogenous surfactant, 85% of infants with respiratory distress syndrome requiring ventilation survive to discharge home and over 90% of survivors are likely to be healthy normal adults. PMID- 8208495 TI - Hepatitis B vaccination. PMID- 8208496 TI - A comparison of the respiratory care given to asthmatic and nonasthmatic children in a general practice. AB - AIM: To compare the management of respiratory problems in asthmatic and nonasthmatic children. METHOD: A comparison of recorded morbidity in clinical records with parental replies to questionnaires for random matched samples of 5 to 9 year old asthmatic and nonasthmatic children from a suburban middle class general practice over the 1990 year. RESULTS: Eighty six percent of parents of asthmatic children and 75% of parents of nonasthmatic children responded. 11% of asthmatic children left the practice without giving a forwarding address. Asthmatic children consulted more often, saw more general practitioners, and were prescribed more antibiotic and asthma related drug items than nonasthmatic children. Asthmatic children were no more likely than nonasthmatic children to have their respiratory system examined at the general practice when well and no more likely to use secondary services. Fifty seven percent of asthmatic children had an asthma drug related prescription written and 22% of asthmatic children had a peak flow recording. Disagreement between records and parental report: 31% of nonasthmatic children were reported by parents to have asthma related symptoms. 31% of these children did not see a general practitioner, 31% were seen for other problems, and 38% were treated for respiratory problems but not diagnosed as asthmatic. Forty nine percent of asthmatic children were reported to be taking daily asthma medication but 38% of these children had not been prescribed their medication in the practice. Fifty one percent of asthmatic children were reported not to be taking daily asthma medication but 50% of these children had been prescribed an asthma drug in the practice. CONCLUSION: Asthmatic and nonasthmatic children have nearly all their respiratory illnesses managed in general practice. In the general practice management of asthma the issues of workload, continuity of care, acute management, practice population based management, and communication need more research. PMID- 8208497 TI - Failure of New Zealand hepatitis B carriers to respond to Phyllanthus amarus. PMID- 8208498 TI - A shared understanding of cancer. PMID- 8208499 TI - A simple explanation of statistical models used in medical research. PMID- 8208500 TI - Reference to a general practitioner. PMID- 8208501 TI - Validity of Maori hospital discharge statistics. PMID- 8208502 TI - Customer satisfaction surveys. PMID- 8208503 TI - Pericardial tamponade: a complication of central venous cannulation. PMID- 8208504 TI - Australian paralysis tick bite. PMID- 8208505 TI - Confidentiality breached. PMID- 8208506 TI - Euthanasia. PMID- 8208508 TI - Doctor-patient relationships. PMID- 8208507 TI - Think before prescribing NSAIDs. PMID- 8208509 TI - Implantable port needlestick injuries and protective devices. PMID- 8208510 TI - Populations and individuals; a view from general practice. PMID- 8208511 TI - Antitumor effect of biological response modifier, PSK, on C57BL/6 mice with syngeneic melanoma B16 and its mode of action. AB - The effects of PSK, a protein-bound polysaccharide, on the survival period and effector cell activity were examined using C57BL/6 mice with melanoma B16. PSK prolonged the survival period of the mice with tumors in a schedule- and dose dependent manner. However, no life-prolonging effect was observed when carrageenan-treated mice or congenitally athymic mice were used as hosts. PSK enhanced the cytostatic activity and interleukin-1-producing capacity of peritoneal exudate plastic-adherent cells in C57BL/6 mice with tumors. These findings suggested that PSK prolongs the survival period of mice with B16 tumors through T-cell- and macrophage-dependent mechanisms. PMID- 8208512 TI - Immunohistochemical detection of the c-myc oncogene product in normal, hyperplastic and carcinomatous endometrium. AB - The expression and the distribution of the c-myc oncogene product (p62) was studied by a 3-step immunoperoxidase technique using the monoclonal antibody myc 1-6 E10 in 22 cases of normal endometrium (11 proliferative and 11 secretory phase), 43 endometrial hyperplasias (24 adenomatous and 19 adenocystic) and 26 endometrial carcinomas. Increased expression of c-myc product appeared in endometrial carcinomas compared with respective non-neoplastic tissue (p < 0.001). The immunolocalization of the c-myc protein shows a consistent difference between the various histologic patterns of non-neoplastic and neoplastic endometrium. Nuclear staining of the c-myc product was demonstrated in epithelial cells of the proliferative phase and predominantly in poorly differentiated forms of endometrial carcinomas. On the other hand cytoplasmic staining was found predominantly in the secretory phase and in well differentiated carcinomatous endometrium. In hyperplastic endometrium an intermediate immunohistochemical pattern was observed. The results of the present study emphasize that c-myc product overexpression and localization plays an important role in initiation, differentiation and progression of endometrial carcinomas. PMID- 8208513 TI - Inhibition of the membrane localization of p21 ras proteins by lovastatin in tumor cells possessing a mutated N-ras gene. AB - Mutated ras genes are found in a variety of human tumors. For biological activity the gene product p21 ras needs to be bound to the cell membrane by a farnesyl residue. Treatment of tumor cells with lovastatin reduces the availability of farnesyl pyrophosphate for the modification of the ras proteins. The membrane localization of p21 ras has been reduced by 30-36% after the tumor cells have grown in the presence of 10 microM lovastatin for 7 days. The extent of the inhibition depends on the growth kinetics of the cell lines. PMID- 8208514 TI - Lymph node-negative breast cancer: the prognostic role and time dependency of age, tumor diameter and mean nuclear area. AB - This study of 786 node-negative breast cancer patients demonstrates that the prognostic effect of age at operation, tumor diameter and mean nuclear area (MNA) changed over time. Identifying patients at higher risk of dying after 5 years may be of clinical importance. These are patients who may have had a low metastatic tumor burden at the time of operation and in whom cytostatic adjuvant treatment could be of value. When estimating 10-year survival, a significant loss of strength was found for age. A near significant loss of effect was also found for MNA, while tumor diameter was the variable best maintaining prognostic power during the observation period. Due to the loss of strength for MNA and age when estimating 10-year survival, the observation period was divided into two periods. When estimating 5-year survival, MNA was the strongest variable, while tumor diameter and age gave additional significant information. When estimating the next 5 years, excluding patients who died before 5 years, only tumor diameter gave significant prognostic information (573 cases). This again stresses the importance of tumor diameter in assessing prognosis in node-negative patients. PMID- 8208515 TI - Evaluation of cathepsin D as prognostic predictor in breast cancer. AB - Cathepsin D is an acidic lysosomal protease expressed in all cells. Some studies have shown correlations between high levels of tissue cathepsin D and poor prognosis. This paper deals with 158 cases of breast cancer in which tissue concentrations in cathepsin D, age, estrogen and progesterone receptor content, and pathological characteristics of the tumor were investigated. Tumors were considered to be cathepsin D+ when a concentration > 40 pmol/mg protein (median value in our samples) was determined. The expression of cathepsin D appears to be related to grading (p = 0.04) and lymph node status (p = 0.05). We found no significant associations among cathepsin D levels, patient age, steroid receptors and histological type. Moreover, the levels of cathepsin D have been evaluated in 9 samples of recurring or metastatic neoplasia and 11 cases of benign breast lesions. We conclude that cathepsin D may be a useful prognostic predictor in breast cancer. Further investigations are required to improve and extend the applications of this assay. PMID- 8208516 TI - Thymidylate synthase activity as a prognostic factor in ovarian cancer. AB - We assayed thymidylate synthase (TS) activity and performed flow-cytometric DNA analyses in fresh tumor tissues from 38 patients with ovarian cancer. TS activity was closely correlated with prognosis but was not related to age, clinical stage, histologic type or lymph node metastases. Patients with TS activity higher than 2.0 pmol/g tissue had significantly worse prognoses than those with lower levels (p < 0.01). Also, patients with DNA aneuploidy or high S-phase fractions (> 20%) had worse prognoses than those with DNA diploidy or lower fractions. Results suggest that TS activity may be a good prognostic indicator in ovarian cancer. PMID- 8208517 TI - Hydralazine combined with hyperthermia enhances the effects of carboquone. AB - Carboquone (CQ) and hyperthermia (HT) are capable of preferentially killing oxygen-deficient cells, both in vitro and in vivo. We examined effects of the combination of CQ and HT on an in vitro hypoxic system and on murine solid tumors using hydralazine (HYD), a vasoactive agent. Under in vitro hypoxic conditions, the combined cytotoxicity of CQ and HT (43 degrees C, for 1 h) was enhanced and the enhancement ratio (ER) for the IC90 of CQ was 21.4-, 9.4-, and 2.6-fold compared to that for CQ alone, CQ under hypoxic condition, and CQ plus HT under aerated cells, respectively. Five mg/kg i.p. HYD reduced the level of tumor blood flow in mice to about 20% of constant level and this reduction persisted for 1 h. In mice bearing B16 melanoma tumors, HYD enhanced tumor susceptibility of the combined therapy of CQ and HT. The ER which was a comparison of tumor growth time in the control group, was 2.3, 3.6 for the two combination groups of 1, 2 mg/kg i.p. CQ, HT (43 degrees C for 20 min), and 5 mg/kg i.p. HYD, respectively. Thus, hyperthermochemotherapy using CQ combined with HYD, seems to selectively attack a solid tumor. PMID- 8208518 TI - Efficacy of the concomitant administration of the pineal hormone melatonin in cancer immunotherapy with low-dose IL-2 in patients with advanced solid tumors who had progressed on IL-2 alone. AB - Our preliminary studies in humans have shown that the pineal neurohormone melatonin (MLT) may enhance the antitumor activity of IL-2, by confirming the existence of a neuroendocrine control on cytokine effects. On this basis, a study was started to evaluate the influence of a concomitant administration of MLT and low-dose IL-2 in cancer patients, who had progressed during a previous immunotherapy with IL-2 alone. The study included 14 patients with advanced solid tumors (lung 6; kidney 4; stomach 2; liver 1; melanoma 1). IL-2 was given at a daily dose of 3 million IU s.c. for 6 days/week for 4 weeks. MLT was given orally at a daily dose of 40 mg every day, starting 7 days prior to IL-2. Objective tumor regression, consisting of a partial remission (PR), was achieved in 3/14 (21%) patients (lung 1; kidney 1; liver 1). Six other patients had a stable disease (SD), while the remaining 5 cases progressed. PR and SD were associated either with a significantly longer survival at 1 year, or with a significantly higher increase in lymphocyte and eosinophil mean number with respect to the patients with disease progression. This preliminary study suggests that advanced solid neoplasms resistant to IL-2 may become responsive to IL-2 therapy by a concomitant administration of the pineal hormone MLT, which could act by enhancing IL-2 antitumor immune effect and/or by increasing the susceptibility of cancer cells to the cytolysis mediated by IL-2-induced cytotoxic lymphocytes. PMID- 8208519 TI - Treatment of malignant pleural mesothelioma with cisplatin, mitomycin C and alpha interferon. AB - From October 1990 to September 1991, 20 consecutive patients with histologically proven malignant pleural mesothelioma (MPM), secondary to environmental exposure to asbestos or erionite, were treated with cisplatin, mitomycin C and alpha interferon (cisplatin 50 mg/m2 i.v. on day 1 of a 21-day cycle; mitomycin C 10 mg/m2 i.v. day 1 of cycles 1,3 and 5; alpha-2b-interferon 10 x 10(6) units i.m., 4 h prior to cisplatin and 10 x 10(6) units i.v. immediately prior to cisplatin day 1 of each cycle). Eighty-two treatment cycles were administered to 19 evaluable patients. Two patients attained a partial response. Eleven patients had stable disease and 6 had disease progression. Toxicities included interferon related fever and flu-like symptoms, and vomiting. Actuarial median survival was 15 months. Three patients are alive at 20+, 21+ and 27+ months. We conclude that while the addition of alpha interferon to cisplatin and mitomycin C did not result in an objective response higher than previously reported with the cytotoxic agents alone, the trend towards an improvement in median survival as compared to a well-matched historical group suggests some benefit from the inclusion of interferon. PMID- 8208520 TI - Phase II trial of cisplatin and etoposide as first-line therapy in metastatic breast carcinoma. AB - Twenty-two patients with metastatic breast carcinoma were treated with a combination of cisplatin (100 mg/m2 i.v. day 1) and etoposide (100 mg/m2 i.v. days 1-3). Eligible patients had measurable disease with normal organ functions, performance status < 3, age < 70 years and no previous chemotherapy for metastatic disease. Twenty patients were assessable for response. Objective responses were seen in 50% (95% confidence limits: 24.4-67.8). One patient achieved a complete response. Objective response was observed in patients with visceral metastatic disease and who had received anthracyclin-containing regimens in previous chemotherapy. Median survival after therapy was 55 weeks. Median time to progression was 23 weeks. Hematologic toxicity was limiting. Cisplatin plus etoposide is an active combination in advanced breast cancer. PMID- 8208521 TI - Failure of gonadotropin releasing hormone therapy in patients with metastatic ovarian sex cord stromal tumors. AB - Ovarian sex cord stromal tumors are usually indolent neoplasms that are generally confined to one or both ovaries at the time of diagnosis. The overall prognosis for these women is good though advanced or recurrent tumors occasionally occur. In such instances, if the tumor is localized, surgical or radiation therapy often provides good results; however, diffuse intra-abdominal disease is uncommon and difficult to treat effectively. Recently, synthetic gonadotropin releasing hormone (GnRH) analogue therapy has been advocated as an effective therapy with low toxicity. We report on 2 women whose advanced recurrent ovarian cord stromal tumors failed to respond to repetitive surgical, chemotherapeutic, and GnRH therapies. In these 2 cases, GnRH therapy was not successful in controlling diffuse spread of two separate gonadal stromal tumors. Systemic toxicity was minimal. PMID- 8208522 TI - Recombinant human tumor necrosis factor causes regression in patients with advanced malignancies. AB - Fifteen patients with advanced solid tumors of various types were treated by the intratumoral administration of recombinant human tumor necrosis factor (rH-TNF). The treatment appeared to benefit the 4 cases of superficial tumors: there were 1 complete response, 1 partial response and 2 minor responses. In all 11 patients with deep-seated tumors, including 6 cases of pancreatic cancer, 4 of liver cell cancer and 1 of metastatic liver tumor, no tumor regression was observed, but progression stopped in all these tumors. Seven of the 11 with deep-seated tumors showed a decrease in tumor markers and/or the development of tumor necrosis. Fever, hypotension and fatigue were the main clinical side effects. No significant changes were found in hematologic, renal or liver parameters. These results suggest that administration of rH-TNF to the tumor site has the potential for controlling local tumor growth. PMID- 8208523 TI - Analysis of 390 patients surviving 10 years or longer after curative resection for gastric cancer. AB - We analyzed clinicopathological features and prognosis of 390 Japanese patients with gastric cancer who survived 10 years or longer after curative resection. All of the patients were treated in our clinics. One hundred and ninety-one of these patients had early gastric cancer and the other 199 had advanced gastric cancer. The mean age was 53.5 years and the male to female ratio was 2:1. The upper one third of the stomach was less commonly involved and a partial gastrectomy was most often done. Lymph node metastasis was present in 28.7% and extensive lymph node dissection (R2 or R3) was done in 92.5% of the cases. Nine patients died with a recurrence of gastric cancer and 20 patients died with a malignancy in other organs. Curative resection with extensive lymph node dissection and, when required, combined resection of the neighboring organs does improve the survival rate for patients with either early or advanced gastric cancer. An annual follow up examination to rule out recurrences or malignancies in other organs is to be recommended. PMID- 8208524 TI - Prophylactic external irradiation in differentiated thyroid cancer: a retrospective study over a 30-year observation period. AB - Following surgery which left no microscopic residue, 114 patients with differentiated thyroid cancer (58 papillary, 56 follicular) were subgrouped on the basis of the dose of externally applied prophylactic postoperative radiation: group 1 received an adequate dose of radiation (> or = 4,500 cGy of telecobalt, > or = 4,000 R of orthovoltage therapy), while group 2 received an inadequate dose of radiation (this group included non-irradiated patients). Local/regional relapse-free survival (LRRFS), distant-metastatic-relapse-free survival (DMRFS) and total-cause-specific survival (TCSS) were calculated by means of life-table analysis for each histologic type. TCSS and LRRFS were significantly (p < 0.001) better for group 1 in papillary cancer. No difference was found in DMRFS. LRRFS was significantly (p < 0.001) better for group 1 in follicular cancer. No differences were found in TCSS and DMRFS. We conclude that (1) prophylactic postoperative external irradiation is an effective method for survival prolongation in papillary cancer, reducing local/regional recurrences, and (2) external irradiation should be considered in the postoperative management of follicular cancer, to diminish local/regional relapse. PMID- 8208525 TI - Consensus conference on breast cancer screening. Paris, February 4-5, 1993. Report of the Evaluation Committee. PMID- 8208526 TI - Molecular controls of apoptosis: differentiation/growth arrest primary response genes, proto-oncogenes, and tumor suppressor genes as positive & negative modulators. PMID- 8208527 TI - Gene regulation of trkB and trkC in the chick retina by light/darkness exposure. AB - The trk gene family members; the neurotrophic receptors for neurotrophins, are implicated in the survival and the differentiation of neurons. The roles of these protooncogenes have been argued in the pathological conditions and in the specific developmental stage when the programmed cell death occurs to neurons. Here we studied a physiological role of the trk family members in the retina through observations of their gene regulation by light/darkness exposure. Northern blot analysis and immunohistochemistry demonstrate that trkB and trkC are up-regulated by light exposure and down-regulated by darkness in the rod/cone layer, the outer nuclear layer, and the ganglion cell layer. This physiological regulation suggests that these trk family members play a protective role from the damaging effect of light exposure in the retinal neurons. PMID- 8208528 TI - Effect of UV-irradiation on cell cycle, viability and the expression of p53, gadd153 and gadd45 genes in normal and HPV-immortalized human oral keratinocytes. AB - We previously demonstrated neoplastic conversion of HPV-immortalized human oral keratinocytes by exposing cells to chemical carcinogens, but failed to transform normal human oral keratinocytes with same chemical carcinogens in vitro. Though the reason for different responses of normal and HPV-immortalized oral keratinocytes to chemical carcinogens remains speculative, the difference may be due to the capacity of normal cells and incapacity of HPV-immortalized cells for repairing damaged DNA induced by carcinogens. Since (1) the repair of damaged DNA takes place in G1/G2 phases of cell cycle, (2) wild type p53 plays major role in the induction of transient G1 and/or G2 arrests, and (3) the expression of gadd45 and gadd153 is also associated with the cell cycle arrest and DNA damage, we investigated transient cell cycle arrest and the expression of p53, gadd45 and gadd153 in normal human oral keratinocytes, HPV-immortalized oral keratinocytes, and an oral cancer cell line expressing mutant p53 after exposing cells to UV light. Normal cells demonstrated transient G1 arrest after exposure to UV light, but other tested cells did not. While UV-irradiation significantly increased the level of intranuclear wild type p53 protein in normal cells, it did not alter p53 protein levels in HPV-immortalized and oral cancer cells. The level of gadd45 transcripts was enhanced in all tested cells, but normal cells demonstrated higher increase in the level of gadd45 after UV-exposure compared to other tested cells. The level of gadd153 gene transcripts was only increased in normal oral keratinocytes after UV-irradiation. These data indicate that UV-induced transient G1 arrest in normal oral keratinocytes may be associated with both enhanced levels of intranuclear wild type p53 protein and gadd45 and gadd153 transcripts. PMID- 8208529 TI - The retinoblastoma binding factor 1 (RBF-1) site in RB gene promoter binds preferentially E4TF1, a member of the Ets transcription factors family. AB - The tumor suppressor retinoblastoma gene product, pRB, is a well known regulator of G1/S cell cycle progression. Moreover, mutational inactivations within the retinoblastoma gene (RB) are found in many human malignant tumors, and thus, believed to be an essential step in tumor formation. The human RB gene is considered as a housekeeping gene with no characteristic TATA or CAAT elements in its promoter region, but the sequence between 206 and 185 bases upstream of the initiation codon, essential for RB promoter activity, contains putative Sp1 and ATF recognition sites. We have previously reported that point mutations in this region, causing low penetrance retinoblastomas, completely reduced RB promoter activity, and that a nuclear factor, named RBF-1 (retinoblastoma binding factor 1), could specifically bind to this sequence, overlapping Sp1 recognition sequence. We show here, that RBF-1 can recognize a specific DNA sequence, 5' GGCGGAAGT-3', overlapping the Sp1 and ATF sites and corresponding to the consensus DNA binding site for members of Ets transcription factors family. When RBF-1 site was used for sequence specific DNA affinity purification from erythroleukemia cells, reconstitution assays, immunoblotting analysis and peptide mapping show that the two major co-purified proteins are identical to human E4TF1 60 and -53 proteins. This reveals that E4TF1 can bind to the RBF-1 site of RB gene promoter, which, thus, constitutes a new target for this member of Ets transcription factors family. PMID- 8208530 TI - Lineage specific demethylation of tal-1 gene breakpoint region determines the frequency of tal-1 deletions in alpha beta lineage T-cells. AB - tal-1 deletions are caused by a site specific recombination, which exclusively occurs in 12-26% of T-cell acute lymphoblastic leukemias (T-ALL). In a previous study on a large series of T-ALL we demonstrated an apparent preferential occurrence of tal-1 deletions in CD3- and CD3+ alpha beta lineage T-ALL with TcR delta gene deletions on one or both alleles. In the present study we investigated whether accessibility of the tal-1 deletion breakpoint regions influences the preferential occurrence in specific T-ALL subgroups. Because DNA methylation is assumed to determine accessibility of DNA for recombination, the methylation status of the tal-1 deletion type 1 breakpoint regions (sildb and taldb1) was studied. Although the sildb were completely demethylated in all T-ALL, preferential (de)methylation configurations of the taldb1 were observed in the analysed 119 T-ALL. Most TcR-alpha beta + T-ALL contained completely demethylated taldb1 (77%), whereas in most TcR-gamma delta + T-ALL partial or complete methylation occurred (42% and 47%, respectively). In T-ALL subgroups defined by different TcR-delta gene configurations also preferential taldb1 (de)methylation patterns were seen, which was most prominent in T-ALL with both TcR-delta genes deleted (84% complete demethylation). The previously observed preferential occurrence of tal-1 deletion type 1 in TcR-alpha beta + vs CD3- T-ALL and in T ALL with both vs one TcR-delta genes deleted, disappeared when we retricted to T ALL with completely demethylated taldb1. Moreover, all T-ALL with a tal-1 deletion type 1 (n = 15) contained completely demethylated taldb1. We therefore conclude that complete demethylation of taldb1 is a prerequisite for tal-1 deletions type 1 and that the differences in tal-1 deletion frequencies observed in the various T-ALL subgroups are caused by differences in the (de)methylation status of taldb1 in these subgroups. PMID- 8208531 TI - elk-1 proteins interact with MAP kinases. AB - Mitogen activated protein kinases (MAP) or extracellular signal regulated protein kinases (ERK) are a family of protein serine/threonine kinases that are activated very rapidly in response to many extracellular stimuli. elk-1, an ets related gene codes for two transcriptional factors elk-1, which regulates c-fos transcription and delta elk-1, both of which are substrates for MAP kinases. A part of the C-terminal transcriptional activation domain (ETA-2) which is common to both the proteins was previously shown to function as an activator of MAP kinases. In this report, in an attempt to investigate the mechanism of activation of MAP kinases, purified preparations of recombinant elk-1 and P44mpk/ERK-1/ERK-2 proteins were used to show the association of elk-1 proteins with MAP kinases. The specific interactions of elk-1 proteins with MAP kinases were confirmed by co immunoprecipitation studies. Thus elk-1 proteins appear to regulate the activity of MAP kinases by interacting with them ensuring a conformational change and stimulating their autophosphorylation and activation property. The activation was dependent on the presence of ATP and Mg2+. In vitro phosphorylation of elk-1 protein was not regulatory for autonomous DNA binding activity of elk-1 protein. Cells which were exposed to EGF showed a rapid stimulation of an elk-1 specific kinase activity, probably MAP kinase which phosphorylated MBP and was found to be associated with immobilized GST-elk-1. Furthermore, dephosphorylation studies indicate that elk-1 proteins can activate only tyrosine phosphorylated MAP kinase. These results demonstrate the presence of an alternative pathway/mechanism (other than MAP kinase kinase, MAPKK/Mek) for the activation of MAP kinases with tyrosine phosphorylation occurring before serine/threonine autophosphorylation and activation by elk-1 proteins. PMID- 8208532 TI - Mutational analysis of HPV-18 E6 identifies domains required for p53 degradation in vitro, abolition of p53 transactivation in vivo and immortalisation of primary BMK cells. AB - The two major transforming proteins of oncogenic human papillomaviruses are encoded by the E6 and E7 oncogenes. Both viral proteins interact specifically with the products of cellular human tumour suppressor genes; E6 with p53 and E7 with Rb. However, the mechanism of action of E6 is still poorly understood in comparison with that of E7. Although extensive in vitro studies have been done with mutant E6 proteins, very little is known about the activities of E6 in vivo. In this study we have analysed the structure-function relationships of HPV-18 E6 in in vitro analyses and we correlate this with in vivo activity. These studies define a number of domains on the E6 molecule which are involved in the ability of E6 to target p53 for degradation in vitro. This analysis demonstrates that domains previously shown to be important in HPV-16 E6 (Crook et al., 1991; Mietz et al., 1992) are also conserved in HPV-18 and also reconciles the differences between these reports. A series of in vivo studies demonstrate that E6 mediated degradation of p53 in vitro is irrelevant both for cell transformation and for the ability of E6 to abolish p53 transcriptional activation. In addition, we show that at least four distinct regions of the E6 protein are involved in the p53 association in vivo. PMID- 8208533 TI - Terminal differentiation and apoptosis in experimental lung metastases of human osteogenic sarcoma cells by wild type p53. AB - Human SAOS-2 osteogenic sarcoma cells are not metastatic in nude mice and do not express p53. We have selected a variant line (SAOS-LM2) that is tumorigenic and metastatic in nude mice. These cells were transfected with the p53 wild-type (p53wt) or mutated (p53mut 143A) gene, whose expression was verified by reverse transcriptase PCR, cDNA sequencing, and protein immunoprecipitation. Cells were injected i.v. into nude mice, and 4 months later, the mice were necropsied. All cell lines produced a similar number of visible lung metastases, albeit of different sizes. Microscopic examination revealed that most lung metastases in mice injected with p53wt cells (but not p53mut 143A or control cells) consisted of osteoid matrix and apoptotic cells. Expression of either p53wt or p53mut 143A verified the origin of the metastases. These data suggest that transfection of SAOS-LM2 cells with p53wt is associated with in vivo induction of terminal differentiation and apoptosis that inhibit progressive growth of metastases. PMID- 8208534 TI - Escape from senescence in human diploid fibroblasts induced directly by mutant p53. AB - Cellular senescence is thought to be a key restraint on the progression of human tumours, escape from which involves loss of function of tumour suppressor genes. The number and nature of the genes involved however is uncertain, in particular the role of p53 mutation, which is commonly correlated with tumour progression. To address this question, we used the novel approach of directly assessing the effect of mutant p53 on 'pre-aged' human diploid fibroblasts (HDF), thereby avoiding the uncertainty of additional cooperating events, inherent in transgenic models. HDF were passaged till near-senescent and then infected with an amphotropic retroviral vector encoding an ala143 human mutant p53. The results show conclusively that p53 mutation alone is sufficient to extend the proliferative lifespan of normal fibroblasts by approximately 17 population doublings, but has no phenotypic effect on 'young' fibroblasts. We conclude that a key tumour-limiting function of wild-type p53 is to mediate growth arrest after a given number of cell divisions, in agreement with data implicating a p53 regulated gene, WAF-1/sdi-1, in cellular senescence. This may be reconciled with its 'guardian of the genome' role, if telomere erosion, a key change in senescence, is perceived by the cell as a form of DNA 'damage'. PMID- 8208535 TI - Characterization of recombinant Xenopus MAP kinase kinases mutated at potential phosphorylation sites. AB - Xenopus mitogen-activated protein kinase kinase (MAPKK) previously inactivated with protein phosphatase 2A can be reactivated by serine phosphorylation catalyzed by a partially purified MAPKK kinase (MAPKK-K), and is phosphorylated by MAPK on a threonine residue. The sequence analysis of a threonine phosphorylated tryptic peptide of Xenopus MAPKK from mature oocytes suggested that Thr388 is phosphorylated in vivo. A mutant MAPKK that has Thr388 changed to Ala (T388A-MAPKK) was not phosphorylated by purified MAPK, indicating that Thr388 is phosphorylated by MAPK. We then produced and analysed MAPKKs mutated at potential serine phosphorylation sites (S218A-MAPKK and S222A-MAPKK). The wild type MAPKK (WT-MAPKKK), T388A-MAPKK and a kinase-deficient (K97S)-MAPKK were phosphorylated efficiently by MAPKK-Ks purified from Xenopus eggs, and WT-MAPKK and T388A-MAPKK became activated. In contrast, neither S218A-MAPKK nor S222A MAPKK was phosphorylated and activated efficiently by the Xenopus MAPKK-Ks. Similarly, WT-MAPKK, but not S218A-MAPKK or S222A-MAPKK, was activated efficiently by an active Raf-1 immunoprecipitate. However, when the recombinant STE11, a putative MAPKK-K in S. cerevisiae, was used as a source of MAPKK-K, S218A-MAPKK as well as WT-MAPKK, but not S222A-MAPKK, was phosphorylated and activated. Furthermore, replacement of Ser222 with an acidic residue (S222E) elevated substantially the basal kinase activity of MAPKK, while replacement of Ser218 (S218E) did not. These results may suggest an essential role for Ser222 phosphorylation in activating Xenopus MAPKK. PMID- 8208536 TI - Transactivational and DNA binding abilities of endogenous p53 in p53 mutant cell lines. AB - Cells with divergent mutant alleles of the p53 gene have different biological and biochemical properties in vitro. Increasing evidence indicates that p53 is a transcriptional activator, and recently, high affinity DNA binding sites for p53 have been identified. The purpose of this study was to determine in vivo, the effect that various mutant p53 proteins have on their ability to mediate transactivation and to bind specifically to DNA. Either a p53 responsive or control reporter gene was transfected into 18 human carcinoma cell lines, having various p53 mutations, either with or without a wild-type p53 expression vector. The CAT activity and DNA gel retardation were studied to measure transactivation and DNA binding by these endogenous p53s. As expected, the endogenously produced wild-type p53 binds to DNA binding sequences and can transactivate a reporter construct containing a p53 high affinity DNA binding site. Four of five cell lines with homozygous p53 mutations at codon 273 (273His), contained p53 which had the ability to bind to p53 DNA binding sequences and transactivate. In contrast, all the homozygous, non-codon 273 mutant p53s (156Pro, 175His, 223Leu, 248Gln, 248Trp, 280Lys) present in the other cell lines had no transactivating ability. These findings suggest that the biology of cancers with mutations at codon 273 may be different than those with p53 mutations at other sites. The p53 from WRO, a thyroid carcinoma cell line with p53 mutation at codon 223 (223Leu), was able to bind p53 DNA recognition sequences, but was unable to transactivate. Interestingly, in a vulvar carcinoma cell line (A431) with a p53 mutation at codon 273 (273His), the p53 was unable to transactivate and gave an aberrant band on gel retardation. Both CEM and SK-UT-1, which have compound heterozygous mutations at codons 175/248 (175His/248His), produced p53 which can complex with DNA, as well as transactivate. In contrast, the p53 in cell lines with either homozygous 175His or 248His p53 mutations, were unable either to transactivate or bind to the p53 response element. A cell line (NPA) heterozygous for 266Glu p53 mutation, was able to efficiently transactivate a reporter containing a p53 DNA binding site, therefore showing no evidence of a dominant negative effect of the endogenous p53 mutant allele. In summary, this in vivo study further supports the idea that different p53 mutant alleles have various properties which may affect their function. PMID- 8208537 TI - Immortalization of BALB/c mouse embryo fibroblasts alters SV40 large T-antigen interactions with the tumor suppressor p53 and results in a reduced SV40 transformation-efficiency. AB - In order to analyse the immortalizing and transforming potential of simian virus 40 (SV40), we compared the transformation efficiencies of SV40 in primary and in established BALB/c mouse fibroblasts. Five independently isolated clones of freshly immortalized normal fibroblasts (FTE cells) were established from precrisis BALB/c mouse embryo fibroblasts (pMEF cells) according to the protocol for establishing 3T3 cells (Todaro & Green, 1963). These cells expressed a wild type p53 and were indistinguishable in all parameters analysed from original 3T3 cells kept in our laboratory. Using abortive infection to control gene dosage, followed by selection of transformed cells by cloning in soft agar, SV40 was able to transform primary cells with a much higher efficiency than 3T3 or FTE cells. Analysis of this unexpected result revealed that the different transformation efficiencies of SV40 in primary and established cells correlated with an altered cellular response to SV40 infection regarding metabolic stabilization of p53 complexed to large T during abortive infection. Whereas p53 in pMEF cells became stabilized upon abortive infection with SV40, p53 in 3T3 and FTE cells remained unstable. Our results strongly favour the hypothesis that metabolic stabilization and the ensuing higher levels of p53 in abortively infected cells enhance the transforming competence of large T. PMID- 8208538 TI - Vav binds to several SH2/SH3 containing proteins in activated lymphocytes. AB - In T lymphocytes, several proteins are rapidly phosphorylated on tyrosine after stimulation. In this study we examine the ability of tyrosine phosphorylated proteins from Jurkat T cells stimulated by CD2 or T cell receptor-CD3 to interact with the src homology 2 or src homology 3 domains from eight different proteins involved in signal transduction in lymphocytes: Vav, Shc, Nck, phosphatidylinositol-3-kinase, phospholipase C-gamma 1, Ras-GTPase activating protein, c-Crk and Grb2. Our data show that different SH2 domains have distinct patterns of binding to phosphotyrosine containing proteins. We show that Vav, a protein expressed only in hematopoietic cells that may have guanine nucleotide releasing factor activity, is able to interact with certain SH2-containing proteins depending on its tyrosine phosphorylation and with Grb2 in a manner independent of phosphorylation on tyrosine. Coimmunoprecipitation experiments support the idea of a trimolecular complex Shc-Grb2-Vav in vivo. These data suggest a central role played by Vav and provide insight in the complexity and specificity of protein-protein interactions in the signaling events in lymphocytes. PMID- 8208539 TI - A truncated cyclin D1 gene encodes a stable mRNA in a human breast cancer cell line. AB - The G1 cyclin D1 is amplified in approximately 20% of human breast cancers and is frequently overexpressed as part of an amplicon in these tumors, suggesting a potential role for this gene in the pathogenesis of breast cancer. Although amplification of cyclin D1 occurs in human breast cancer, it is possible that another gene in the amplicon is the relevant oncogene in these cancers. We now report a truncation of the cyclin D1 gene in a human breast cancer cell line, associated with overexpression of a short cyclin D1 mRNA. In a survey of breast cancer cell lines and tumors by Southern blot hybridization, using a 1.2 kb human cyclin D1 cDNA, we observed that genomic DNA derived from the MDA MB-453 cell line contains an extra band in the Bg1II and BamHI digests, suggesting that one allele of gene is altered. Moreover, the altered allele is amplified three-fold relative to the normal allele, and contains a 3' deletion. On Northern analysis, the MDA MB-453 line has a marked increase in 1.1 to 1.3 kb transcripts, which are truncated at the 3' end, in contrast to the normally predominant 4.2 kb transcript. The 1.1-1.3 kb cyclin D1 mRNA has a longer half-life than the 4.2 kb mRNA, indicating that the 3' truncation may contribute an increased stability and therefore an elevated steady-state level of the short mRNA. These alterations in the cyclin D1 gene and mRNA suggest that altered expression of cyclin D1 may be important in the malignant transformation of this cell line, and support the identification of cyclin D1 as a dominant oncogene at 11q13 in human breast cancer. PMID- 8208540 TI - Rearranged NFKB2 gene in the HUT78 T-lymphoma cell line codes for a constitutively nuclear factor lacking transcriptional repressor functions. AB - Rearrangements of the NFKB2 gene are associated with lymphoid malignancies, but the functional significance of these alterations is not known. Here we characterize structurally and functionally a rearranged NFKB2 gene identified at the T cell lymphoma line, HUT78. The rearrangement has truncated NFKB2 sequences within the 3' ankyrin domain, leading to the production of truncated mRNA species and proteins as detected by Northern blot and immunoprecipitation analysis, respectively. Cloning and sequencing of the corresponding cDNAs indicates that, via alternative splicing, the rearranged gene codes for two proteins of 84 and 85 kD (p84/85) which retain the DNA-binding rel domain and the first five ankyrin repeats, but have lost their carboxy-terminus including the seventh ankyrin repeat. Immunofluorescence and immunoprecipitation analysis of HUT78 cells indicate that p84/85 are abnormally located in the nucleus in an unprocessed form, suggesting that these proteins can escape the cytoplasmic retention typical of the normal NFKB2 p100 protein before it is processed into p52. Electrophoretic mobility shift assays performed on HUT78 nuclear extracts indicate that the abnormal NFKB2 proteins bind kappa B sites specifically and alter the composition of NF-kappa B complexes in HUT78 cells. Transient co-transfection assays involving NFKB2 expression vectors and kappa B-driven reporter plasmids indicate that NFKB2 p85 has lost the transcriptional repressor functions typical of normal NFKB2 p52. These data indicate that the NFKB2 gene rearrangement detected in HUT78 cells leads to the production of abnormal NFKB2 proteins capable of altering the function of the NF-kappa B transcription system. Since analogous rearrangements are found in lymphoid malignancies, these findings further support a role of NFKB2 alterations in tumorigenesis. PMID- 8208542 TI - Antisense c-jun overcomes a differentiation block in a murine erythroleukemia cell line. AB - We have studied the expression of the c-jun gene during dimethyl-sulfoxide (DMSO) induced differentiation of Friend erythroleukemia (F-MEL) cells. No expression of c-jun was detected in a differentiation-competent F-MEL cell line (745A) either before or after treatment with DMSO. By contrast, c-jun expression was constitutive in a F-MEL cell line (TFP10) resistant to DMSO-induced differentiation and increased with DMSO. We have investigated the possible role of c-jun in conferring this resistance by stably transfecting either sense or antisense c-jun constructs into both differentiation-sensitive 745A and defective TFP10 cell lines. Inhibition of c-jun expression by antisense transcripts in the TFP10 cells restored their ability to undergo erythroid differentiation when exposed to DMSO while expression of junB or junD antisense vectors failed to do so. In addition, c-jun overexpression in the 745A cells resulted in decreased DMSO-induced differentiation. These results indicate a correlation between the level of c-jun expression and the ability of F-MEL cells to undergo DMSO-induced differentiation and suggest that c-Jun may be an important negative regulator in this process. PMID- 8208541 TI - Identification of illegitimate recombination hot spot of the retinoic acid receptor alpha gene involved in 15;17 chromosomal translocation of acute promyelocytic leukemia. AB - Acute promyelocytic leukemia (APL) has been characterized by 15;17 chromosomal translocation, which involves the retinoic acid receptor alpha (RARA) gene on chromosome 17 and the PML gene on chromosome 15. The breakpoints have been mapped to three cluster regions in the PML gene, and to RARA gene intron 2. We have examined the distribution of breakpoints within RARA gene intron 2. An extremely restricted region (ERR) of 50 bp within RARA gene intron 2 was identified as the cluster region of breakpoints by polymerase chain reaction and sequence analysis of DNA from APL patients. To study experimentally the mechanism involved in the translocation, ERR was tested in NIH3T3 cells by in vitro transfection recombination assay, in which target sequences were placed either downstream of the SV40 promoter or upstream of the neo gene. Cells were conferred resistance to G418 only when the promoter was fused to the neo gene by recombination of two target sequences during transfection. The molecular junctions were analysed in five clones, and all of them were shown to be confined within a 20 bp region in a 148 bp DNA fragment containing ERR. This suggests that ERR might be the illegitimate recombination hot spot in mammalian cells. PMID- 8208543 TI - Lens expression of TGF alpha in transgenic mice produces two distinct eye pathologies in the absence of tumors. AB - Transgenic mice carrying the rat TGF alpha minigene linked to the alpha A crystallin promoter were generated to investigate the effects of expression of this growth factor in the lens of the eye. All transgenic mice exhibited eye abnormalities in the absence of overt tumors, and two distinct and heritable phenotypes were observed. Five lineages produced 'squinting' transgenic mice characterized by microphthalmic eyes with severe lens and retinal dysplasia, and four lineages produced 'bulged' transgenic mice with eyes that exhibited enlarged globes, lens epithelial hyperplasia, anterior segment dysgenesis, and in some cases retinal dysplasia. The eye perturbations of both phenotypes were evident histologically by 1 week of age, and the eyes of squinting mice were abnormal during embryonic development. The squinting phenotype was dominant over the bulged phenotype in intercrosses, suggesting that position effects from the transgene integration site resulted in differences in TGF alpha expression between the two phenotypes. In situ hybridization showed that TGF alpha transgene expression was confined to the lens or lens rudiment of all transgenic eyes despite the involvement of non-lenticular tissues in the pathology. These results show that inappropriate expression of TGF alpha in the eye can disrupt the communication required to coordinate normal eye development. PMID- 8208544 TI - Two novel human serine/threonine kinases with homologies to the cell cycle regulating Xenopus MO15, and NIMA kinases: cloning and characterization of their expression pattern. AB - Using polymerase chain reaction (PCR)-based methods, we have isolated cDNA clones of two new members of serine/threonine kinases, STK1 and STK2, from a cDNA library constructed from the BT-20 human breast cancer cell line. STK1 is transcribed as a 1.4 kilobase (kb) mRNA encoding for a protein of 346 amino acids. Based on amino acid sequence analysis, STK1 is 86% identical to the Xenopus p40mo15, a cdc2-related serine/threonine kinase recently found to be the activating kinase for p34cdc2 and p33cdk2. Thus, STK1 is most likely the human homologue of MO15. An alternatively spliced STK1 message expressed variably in cell lines and in primary carcinomas generates a predicted 58 amino acid protein that lacks the kinase domain. STK2 is transcribed into a 4.0 kb mRNA encoding for an 841 residue protein which exhibits 50% identity in the kinase domain with the mouse nek1 gene product, the relative of the fungal G2-M regulator, nimA. STK1 and STK2 display a variable pattern of expression among a series of primary carcinomas as well as cancer cell lines. Both STK1 and STK2 were expressed at the highest levels in the heart but were also detected in all other organs tested. In embryonal tissues, lower levels of expression were noted. Using cell cycle inhibitors, we have shown that both STK1 and STK2 mRNA levels remain relatively invariant through the cell cycle. Chromosomal assignment has localized STK1 on chromosome 2pcen-2p15, a region implicated in hereditary non-polyposis colorectal carcinoma, and STK2 on chromosome 3p21.1, a region frequently showing chromosomal alterations in renal cells carcinomas. PMID- 8208545 TI - Phorbol esters support the proliferation of a hematopoietic cell line by upregulating c-jun expression. AB - FD/PMA, a derivative of the interleukin-3 (IL-3) dependent FDC-P1 cell line, proliferates in response to either phorbol esters (phorbol 12-myristate 13 acetate, PMA) or IL-3. Analysis of immediate-early gene expression revealed that FD/PMA cells contained elevated levels of c-jun transcripts when grown in the presence of phorbol esters. Upregulation of c-jun mRNA was specific since other jun family members (namely jun-B and jun-D) displayed similar patterns of gene expression as observed in the parental cell line. The accumulation of c-jun RNA was due to increased c-jun transcription and not the result of altered message stability. Furthermore, elevated c-jun expression resulted in increased AP-1 binding activity in FD/PMA cells. Antisense c-jun oligonucleotides suppressed proliferation of FD/PMA cells by 80% and resulted in a significant reduction in both AP-1 binding activity and c-jun message levels. Collectively, these results demonstrate that FD/PMA cells require elevated levels of c-jun expression for PMA responsive proliferation and indicate that tumor promoters have the ability to abrogate IL-3 dependency by elevating AP-1 activity. PMID- 8208546 TI - Differential sensitivity of normal and Ha-ras-transformed C3H mouse embryo fibroblasts to tumor necrosis factor: induction of bcl-2, c-myc, and manganese superoxide dismutase in resistant cells. AB - In this study, we investigated the role of activated Ha-ras oncogene on the growth-regulatory properties of tumor necrosis factor (TNF) in C3H mouse embryo fibroblasts. TNF-resistant 10T1/2 cells transfected with an activated Ha-ras oncogene not only produced tumors in nude mice but also exhibited extreme sensitivity to cytolysis by TNF. TNF-induced cell death was mediated through apoptosis. The differential sensitivity of normal and Ha-ras transformed cells to TNF was not due to differences in the number of TNF receptors on their cell surface. However, TNF-resistant cells, but not sensitive cells, overexpressed bcl 2, c-myc, and manganese superoxide dismutase (MnSOD) mRNA following exposure to TNF. In addition, TNF treatment resulted in a marginal induction of p53 mRNA in both TNF-sensitive and resistant cells. These results suggest that TNF-induced cytotoxicity involves apoptosis and that TNF-induced over-expression of bcl-2, c myc, and MnSOD genes is associated with TNF resistance in C3H mouse embryo fibroblasts. PMID- 8208547 TI - Autophosphorylation modulates the kinase activity and oncogenic potential of the Met receptor tyrosine kinase. AB - The met oncogene is activated by a genomic rearrangement that generates a hybrid protein containing tpr sequences at its amino terminus fused directly to the met (hepatocyte growth factor/scatter factor) receptor tyrosine kinase domain. The resultant p65Tpr-Met hybrid protein possesses tyrosine kinase activity and is constitutively phosphorylated on tyrosine in vivo. A substitution of the conserved lysine in the catalytic domain abolished kinase activity and the transforming potential of Tpr-Met demonstrating the requirement for kinase activity for transformation. To study the role of autophosphorylation at particular tyrosine residues on the transforming activity of Tpr-Met, the major autophosphorylation sites were identified by two dimensional phosphopeptide mapping. Two tyrosine residues in the catalytic domain, tyrosine 365 and tyrosine 366, were found to be the major autophosphorylation sites both in vitro and in vivo. Mutation of these sites singly or together modulates the biochemical and biological properties of Tpr-Met. Compared with the wild-type Tpr-Met, mutants have a reduced in vitro kinase activity when measured by levels of autophosphorylation and by their ability to phosphorylate an exogenous substrate and have little or no transforming activity. These results indicate that autophosphorylation at critical tyrosine residues is required for activation of the kinase activity of Tpr-Met and for cell transformation by this oncogene. PMID- 8208548 TI - E2F-dependent regulation of human MYC: trans-activation by cyclins D1 and A overrides tumour suppressor protein functions. AB - Transcription of the human proto-oncogene MYC is repressed in quiescent or non dividing cells. Upon mitogenic stimulation expression of MYC is rapidly and transiently induced, maintained throughout G1, and declines to a basal level throughout further cell cycle transitions. Regulation of MYC promoter activity critically depends on the presence of a binding site for transcription factor E2F. Human E2F has been implicated also in the control of cell cycle progression through it association with the retinoblastoma suppressor gene product RB, and with multimeric protein complexes containing the G1-S- and S-phase cyclins E and A, respectively. Using CAT reporter co-transfection assays we show here that transcription from the MYC P2 promoter is induced efficiently by E2F-1, but repressed by RB. Furthermore, overexpression of cyclin A strongly activates the MYC promoter and this effect is further enhanced by coexpression of E2F-1 and cyclin A. We also find that expression of G1-phase cyclin D1 leads to an E2F binding site-dependent trans-activation of the MYC promoter and that this activation can be abrogated by overexpression of RB. The interaction of D-type G1 cyclins with RB resembles that of the adenovirus E1A protein with RB in that it can disrupt inhibitory E2F-RB complexes. Our results support a model in which intervention of distinct cyclins and their respective associated kinases promotes transcriptional activation of MYC throughout the cell cycle either by conversion of E2F within multimeric complexes into an active transcription factor or by liberation of free functional E2F. PMID- 8208549 TI - Modulation of c-MET proto-oncogene (HGF receptor) mRNA abundance by cytokines and hormones: evidence for rapid decay of the 8 kb c-MET transcript. AB - The c-MET proto-oncogene product is a transmembrane tyrosine kinase receptor which was recently shown to transmit an array of important cellular responses induced by Hepatocyte Growth Factor (HGF). These biological effects include induction of mitogenesis, motogenesis, morphogenesis, metastogenesis and anti tumor activity on a variety of epithelial cells. All of these processes are known to be associated with normal and abnormal tissue growth and development. The 190 kDa c-MET protein is encoded by a major transcript of 8 kilobases (kb), which is reported to be expressed predominantly in epithelial tissues. The expression pattern of c-MET mRNA and protein are drastically modified in many tumor tissues and cell lines. Currently, no information is available on the molecular mechanisms that regulate c-MET mRNA level. In the present communication, we report for the first time that the inflammatory cytokines such as IL-1 alpha, IL 6 and TNF-alpha, as well as TGF-beta 1, EGF, HGF and the steroidal hormones (estrogen, progesterone, tamoxifen and dexamethasone) markedly influence the steady-state levels of the 8 kb c-MET mRNA in human carcinoma cell lines derived from human tissues such as ovary, breast and endometrium. We demonstrate that c MET receptor protein is present at high levels in primary tumors of human ovaries (clear cell carcinomas). We present evidence that the 8 kb c-MET mRNA undergoes rapid degradation with a half-life of less than 30 min and that this decay can be quickly inhibited by cycloheximide. Our results suggest that the expression of the c-met proto-oncogene resembles that of an immediate early response gene. PMID- 8208550 TI - Tyrosine kinase gene expression in the mouse small intestine. AB - To identify tyrosine kinases that may regulate regeneration of the mammalian intestinal epithelium, we amplified portions of the catalytic domains of protein kinases expressed in intestinal crypt cells, using the polymerase chain reaction technique with primers directed against two invariant amino acid sequence motifs found in all kinases. These fragments were cloned and a library of kinase catalytic domains was generated. Sequence analysis of unique clones resulted in the identification of the catalytic domains of several characterized tyrosine kinases, including lyn, hck, c-fgr, tec, JAK2, itk, and the putative receptor kinase ryk, and expression of these kinases has not previously been described in the intestine. We compared the levels of mRNA encoding these kinases in multiple tissues using RNase protection assays, and we localized the expression of hck, lyn, and JAK2 in the intestine using in situ hybridization. In addition, we identified two novel putative catalytic domain sequences. One of these, which we have named sik (src-related intestinal kinase), is expressed at high levels in the gastrointestinal tract and may play a specific role in signal transduction in epithelial tissues. PMID- 8208551 TI - Cloning of novel Wilms tumor gene (WT1) cDNAs; evidence for antisense transcription of WT1. AB - WT1 is a tumor suppressor gene that has been implicated in Wilms tumor, and is expressed in cells of mesodermal origin. The Wit-1 gene is located approximately 2 kb from the WT1 gene, and is expressed coordinately with WT1. WT1 and Wit-1 are bi-directionally transcribed from the same promoter region. We have screened a human fetal kidney cDNA library to identify novel WT1 cDNA clones. Here we report the cloning of cDNA clones which span part of intron 1 of WT1, exon 1, upstream sequences between WT1 and Wit-1 and part of the Wit-1 gene. Northern blot and RNAase protection analysis using subcloned fragments of the cDNAs corresponding to regions from within intron 1 of WT1 suggest that a 7-10 Kb RNA is expressed in human fetal kidney, which overlaps with WT1 and is transcribed in the same direction as Wit-1. PMID- 8208552 TI - cph, a novel oncogene which cooperates with H-ras in the transformation of NIH3T3 fibroblasts. AB - We have performed the molecular cloning of the non-ras transforming sequences previously detected in neoplastic Syrian hamster embryo fibroblasts initiated in vitro with 3-methylcholanthrene (MCA) (Notario et al., 1990). These sequences were isolated using cosmid-rescue techniques from a third-cycle NIH3T3 transformant obtained by sequential transfections of genomic DNA from MCA initiated hamster fetal cells. Rescued (C-5) clones encompassed about 42.5 kbp of Syrian hamster genomic DNA containing hamster-specific repetitive elements (HRS). An internal 19 kbp BamHI fragment (B-1) was the only C-5 fragment which recognized specific transcripts in poly(A)+ RNA from hamster embryo cells. The same mRNA species were present in both normal and MCA-initiated neoplastic cells: a major transcript of about 2.5 kb, and other less abundant ones, ranging from approximately 2.0 kb to 5.0 kb. These mRNA species were detected consistently by each of several B-1 DNA subfragments located at positions spanning almost the entire B-1 length. The nucleotide sequence of some transcript-positive (S5P2 and S6) genomic B-1 fragments was determined. No significant homology exists between the nucleotide sequences of these B-1 subfragments and established DNA databases. Therefore, the C-5 cosmid clone contains novel genomic sequences. Transfection of C-5 DNA into mouse NIH3T3 cells resulted in the appearance of transformed foci (about five foci per microgram of DNA) within 25 days post-transfection, thus demonstrating the transforming activity of the C-5 clone, which was consequently renamed as the cph oncogene. Co-transfection of the cph oncogene with the human H ras oncogene (T24), demonstrated a synergistic action between the two oncogenes in the transformation of murine fibroblasts. PMID- 8208553 TI - Linear antigenic sites defined by the B-cell response to human p53 are localized predominantly in the amino and carboxy-termini of the protein. AB - Using a set of overlapping peptides of the human p53 protein, we analysed the epitopes recognized by 18 monoclonal antibodies specific for human p53. We showed that most of these epitopes correspond to linear antigenic determinants which lie predominantly in the amino- or carboxy-terminus of the p53 protein. Using either truncated p53 or the set of human p53 peptides, we directly analysed the sera of animals immunized with human p53. These sera contained antibodies which also recognized the regions corresponding to the extremity of the p53 protein. These p53 regions were similar to those recognized by p53-specific antibodies present in sera of patients with cancer. Preferential recognition of these regions by antibodies specific for non conformational epitopes suggested that these regions are localized at the surface of the p53 protein as unfolded structures. PMID- 8208555 TI - Definition of two regions of deletion on chromosome 9 in carcinoma of the bladder. AB - Loss of heterozygosity (LOH) at loci on chromosome 9 can be detected in more than 50% of bladder tumours, suggesting the presence on this chromosome of one or more suppressor genes for bladder carcinogenesis. Localisation of the target gene(s) by deletion mapping has previously proved difficult due to the uneven distribution of polymorphic loci and the finding of LOH at all these loci in the majority of tumours. We have used a panel of 22 highly informative microsatellite markers, evenly distributed along chromosome 9 to analyse LOH in 95 cases of primary transitional cell carcinoma of the bladder. Forty nine tumours (53%) showed LOH at one or more loci. Of these, 30 had LOH at all informative loci, indicating probable monosomy 9. Nineteen tumours (22%) had subchromosomal deletions, 5 of 9p only, 9 of 9q only and 5 of both 9p and 9q with a clear region of retention of heterozygosity between. The patterns of LOH in these tumours indicated a common region of deletion on 9p between D9S126 (9p21) and IFNA (9p21). A single tumour showed a second site of deletion on 9p telomeric to IFNA indicating the possible existence of 2 target genes on 9p. All deletions of 9q were large, with a common region of deletion between D9S15 (9q13-q21.1) and D9S60 (9q33-q34.1). These results indicate a much higher frequency of subchromosomal deletion than has previously been detected and provide evidence for the simultaneous involvement of distinct suppressor loci on 9p and 9q in bladder carcinoma. PMID- 8208554 TI - Loss of heterozygosity studies on chromosome 17 in head and neck cancer using microsatellite markers. AB - In this study we have analysed 38 squamous cell carcinomas (SCC) two basal cell carcinomas (BCC), a malignant salivary gland carcinoma, a neurosarcoma and a Warthins carcinoma, all isolated from patients with head and neck cancers. These tumour types have been examined by PCR for loss of heterozygosity (LOH) on both arms of chromosome 17 using nine polymorphic microsatellite markers. LOH on 17p in SCCHN was found to be 50% (19/38), and often involved TP53 (42%) but more frequently involved the CHRNB1 locus (56%). Twelve tumours showed loss of heterozygosity on 17q (34%) and ten of these also had loss on 17p. Four SCCHN tumours lost an entire copy of chromosome 17. It was of particular note that 77% (10/13) of the SCCHN at the hypopharyngeal site had LOH at CHRNB1. We propose from our data that the 17p12-p11 region contains a novel predisposing gene for hypopharyngeal SCCHN that may function as a tumour suppressor gene. PMID- 8208556 TI - Molecular cloning of the human CAK1 gene encoding a cyclin-dependent kinase activating kinase. AB - Cyclin-dependent, proline-directed protein kinases normally function to execute critical cell cycle transitions; abnormal expression and/or viral subversion of the positive (cyclins) and negative (Pic1) regulatory subunits may contribute to neoplastic transformation and tumorigenesis. In addition to the binding of regulatory subunits, the enzymatic activities of the cyclin-dependent kinases, Cdc2 and Cdk2, are tightly regulated by site-specific protein phosphorylation events. Recent studies have identified a critical phosphorylation site (Thr-161) located within kinase Subdomain VIII that is necessary for Cdc2 activation, and enzymatic activities capable of carrying out this heterologous phosphorylation event have been detected in both Xenopus oocytes and human somatic cells. In this report, we characterize by molecular cloning a human homologue of the Xenopus Cdk activating kinase (Cak, encoded by MO15); the novel human gene is designated (HS)CAK1. While only 75% identity is observed at the nucleotide level, the deduced amino acid sequence encoded by (HS)CAK1 is approximately 87% identical to that of the Xenopus MO15 gene in corresponding regions. The catalytic domain of (HS)Cak1, defined by conserved kinase Subdomains I through XI, exhibits considerable homology with (HS)Cdc2, suggesting that this kinase cascade involves closely related enzymes. Immunological studies with anti-Cak antibodies confirm the presence of specific immunoreactivity in highly purified preparations of the human Cdc2-activating kinase. The molecular characterization of (HS)CAK1 should facilitate studies of its physiological regulation, as well as its potential utility as a target for therapeutic intervention in the treatment of proliferative disorders. PMID- 8208558 TI - Inducible regulatory elements in the human cyclin D1 promoter. PMID- 8208557 TI - PISSLRE, a human novel CDC2-related protein kinase. AB - The cell division cycle have been shown to be regulated by a closely-related family of protein kinases named CDKs (by cyclin-dependent kinases). Using a PCR based cloning technique, we have isolated cDNAs encoding a human CDC2-related protein kinase. The full-length cDNA accommodates an open reading frame that does not contain any ATG initiation codon upstream of the sequence encoding the catalytic domain of this putative kinase. Three putative non-ATG initiation codons have been detected. Starting at the most 5' non-ATG initiation site, the encoded product is 316 amino acids long with a predicted molecular weight of 35.8 kDa. Analysis of the deduced amino acid sequence showed it to contain the XI subdomains present in all known protein kinases and a PSTAIRE-like motive, PISSLRE, which temporarily names this kinase. PISSLRE is most related to p58/GTA (55% identity in the catalytic domain), the galactosyl transferase associated protein, which has been shown to inhibit entry into S-phase when over-expressed in CHO cells. PISSLRE shares 38-45% identity with all CDKs and contains the regulatory Tyr and Thr residues present in most of the members of the CDK family of protein kinases, which suggests similar modes of regulation. PISSLRE is expressed in all human tissues tested, including those which contain high proportion of terminally differentiated cells. However, the levels of the PISSLRE transcripts are dissimilar among different tissues. PMID- 8208559 TI - Myron F. Metzenbaum, MD: innovative surgeon, caring physician. PMID- 8208560 TI - Maurice H. Cottle, MD. PMID- 8208561 TI - Systemic reactions to immunotherapy: the American Academy of Otolaryngic Allergy morbidity and mortality survey. AB - Anaphylaxis may be defined as a systemic, immunoglobulin E-mediated (Gell-Coombs type I) hypersensitivity reaction triggered by exposure to an antigen in a previously sensitized patient. Anaphylaxis may occur in a variety of circumstances; however, when it occurs as the result of immunotherapy, it is of great concern to the practicing allergist. When describing or reporting anaphylaxis relating to immunotherapy, most allergists speak in terms of the types of reactions, local vs. systemic. Germane to this discussion is the use of the term systemic reaction, which can mean anything from mild allergy symptoms resulting from an allergy injection to bradycardia and hypotension (shock). In this article we report serious or significant systemic reactions, which are characterized by any of the following symptoms: urticaria, sneezing or nasal obstruction, throat tightness or congestion, wheezing, and shock (bradycardia or hypotension). There were no fatalities reported from the survey group. The overall reaction rate was 0.3%. PMID- 8208562 TI - Functional endoscopic sinus surgery in patients with chronic sinusitis and asthma. AB - Twenty asthma patients who underwent functional endoscopic sinus surgery for chronic sinusitis were studied. Medical records and questionnaire data for these 20 patients were studied regarding the impact of sinus disease and functional endoscopic sinus surgery on their asthma. We found that 95% reported that their asthma was worsened by their sinus disease (95% confidence interval, 0.74 to 0.99+), and 85% reported that functional endoscopic sinus surgery improved their asthma (0.60 to 0.97). Of the 13 patients who used both inhalers and systemic medication, 53.8% were able to eliminate some of their medication (0.21 to 0.79). Furthermore, 61.5% of these patients had a concomitant reduction in their inhaler use (0.28 to 0.85). All patients (six) who used only inhalers experienced a reduction in their inhaler use (0.54 to 1.00), and two patients were able to eliminate their inhalers completely. One of two patients who were steroid dependent was able to discontinue steroids after surgery. Of patients who used steroids intermittently (13), 53.8% were able to eliminate the use of steroids after surgery (0.21 to 0.79). Patients who required preoperative hospital admissions (4) and emergency room or urgent physician office visits (18) had a 75.0% and 81.3% (p < 0.001) reduction in visits, respectively, after surgery. Because 43% of the cost of asthma is the result of hospitalizations and emergency department/urgent physician office visits, a significant impact on health care costs can be realized with functional endoscopic sinus surgery in this patient population. PMID- 8208563 TI - Malbranchea pulchella fungal sinusitis. AB - Fungal sinus disease is being reported with increasing frequency. We could find no previously reported cases of sinonasal infections with Malbranchea pulchella and only two previously reported cases of human infection of any kind. We now report on a case of suspected sinonasal Malbranchea pulchella in a patient with aspirin-sensitive triad asthma. PMID- 8208564 TI - Functional endoscopic sinus surgery in patients with normal computed tomography scans. AB - Eighteen patients were operated on by functional endoscopic sinus surgery who had no ostiomeatal unit obstruction on computed tomography scan and had unremarkable paranasal sinuses. These patients also had no apparent ostiomeatal unit obstruction on diagnostic nasal endoscopy. Data were collected on these patients regarding the impact of very limited functional endoscopic sinus surgery on their principal complaint of recurrent sinusitis with facial pain/headache thought to be of sinogenic origin. Sixteen patients (88.9%) had a reduction in the number of sinus infections requiring antibiotic therapy. This reduction was significant at p < 0.0001. Twelve of 14 patients whose facial pain/headache was believed to be of sinogenic origin had a significant reduction in severity (95% confidence interval, 49.2% to 95.3%). We discuss the role of reversible nasal mucosal disease in the pathophysiology of recurrent rhinosinusitis in this patient population. This was a very small, select group of patients who had specific complaints and had had medical treatment failures. This therapy is not recommended for every patient, but only a select few with classic complaints of sinus headaches or recurrent sinusitis and negative computed tomography scans. PMID- 8208565 TI - Admission planning and complications of direct laryngoscopy. AB - Increasingly, third party payers are challenging the necessity of a hospital admission for endoscopic procedures. Direct laryngoscopy (DL), with or without open, rigid esophagoscopy or flexible, fiberoptic bronchoscopy, was evaluated for the incidence of perioperative complications and associated risk factors. A retrospective review of 200 in-patient admissions between 1987 and 1990 for direct laryngoscopy or panendoscopy is presented. Complications were classified as major for untoward events that required hospitalization for proper management. Complications were otherwise considered minor. The incidence of major complications was at least 19.5%, with minor complications occurring in 21% of patients. The total population was partitioned into subsets according to the occurrence of major complications, minor complications, and no complications. For the total population and each subset, distributions were developed by age, sex, habitus, physical status level, diagnosis of malignancy, presence of a malignant lesion in the aerodigestive tract, or medical history of head and neck surgery or radiation therapy. Statistical analysis indicates that these parameters do not offer reliable predictors of which patients are at risk for minor or major complications. It is concluded that all patients who undergo direct laryngoscopy are most safely managed in an in-hospital setting for a period on the order of 24 hours. PMID- 8208566 TI - Intralabyrinthine schwannomas. AB - Intralabyrinthine schwannomas are unusual tumors of the vestibule, cochlea, semicircular canals, or some combination of these three, which in the past have been reported as incidental findings at autopsy or surgery. We summarize eight cases of intralabyrinthine schwannomas diagnosed by magnetic resonance imaging at the House Ear Clinic during the past 3 years. We discuss the typical clinical presentation and treatment of cochlear vs. vestibular intralabyrinthine schwannomas. PMID- 8208567 TI - Aspects of facial correction and reconstruction by using transplants (composite grafts and implants) with special reference to surgical membrane implants. AB - This article contains a survey of the methods of facial reconstruction I have used for the past more than 35 years. The advantages of free grafts, especially composite grafts, the place for local flaps or in other areas for defect cover by a combination of flaps and grafts are explained. A few patient examples illustrate the described methods. PMID- 8208568 TI - Auditory and cytocochlear correlates of inner ear disorders. AB - Pure-tone threshold audiograms showing sensorineural hearing loss, when plotted on a data-based anatomic frequency scale, show a close spatial correlation with their respective cytocochleograms. Whereas most of the cochleae show pathology of several different cell types, a sufficient number show losses that involve predominantly a single cell type, which permits the following deductions: (1) focal lesions of the organ of Corti are strongly tonotopic and are responsible for those instances of abrupt pure-tone threshold losses; (2) lesions of the stria vascularis show no tonotopic organization but lead to flat pure-tone threshold losses; and (3) the principal effect of neuronal losses is a diminished capability for word recognition. There is an indeterminate group where no pathologic correlate can be identified by light microscopy. PMID- 8208569 TI - Cranial base surgery: results in 183 patients. AB - OBJECTIVE: To learn about the effects of cranial base surgery. DESIGN: Cohort study with a mean follow-up of 30 months. SETTING: Population-based. PATIENTS: A consecutive sample of 183 patients who underwent cranial base surgery; 118 patients had malignant skull base tumors, the majority of which were previously treated; 50 had benign tumors; 9 had congenital malformations of the skull base; 3 had inflammatory lesions, and 3 had traumatic defects of the skull base. MAIN OUTCOME MEASURES: Disease-free interval, overall survival, and rate of complications and functional status. INTERVENTION: Cranial base surgery was followed by radiotherapy (in previously untreated patients). RESULTS: After completion of follow-up (mean, 30 months), 30 (25.4%) patients had died of their malignant tumors and 8 (6.8%) had died of other causes. One patient (0.84%) was lost to follow-up. The overall cancer survival rate without regard to histologic type was 67% (63% with no evidence of disease). Among the patients who were treated for benign neoplasm, 72% had no evidence of disease at a mean follow-up of 39 months. The group of patients with congenital malformations and inflammatory and traumatic lesions demonstrated successful correction of their presurgical problem with skull base surgery. One patient (who had invasive aspergillosis) died of disease. The overall surgical-medical mortality rate was 2%; the complication rate was 33%, and the Karnofsky performance score was improved or unchanged after surgery in 83% of patients. The average duration of surgery, number of blood transfusions used, and length of the hospital stay were 10 hours, 3 units, and 15 days, respectively. CONCLUSIONS: Cranial base surgery is a valid surgical technique for treatment of cranial base afflictions. In this study it was found to be beneficial in controlling benign and malignant disease and to be the treatment of choice for selected congenital malformations, trauma, and inflammatory lesions. PMID- 8208570 TI - Fetal wound healing. AB - Wound healing research has produced some startling discoveries during the past decade. Foremost among these is the observation that cutaneous wounds created and healed in utero are histologically indistinguishable from intact, unwounded tissue. Observers have documented that the acute inflammatory response and endogenous immunoglobulins that characterize healing in human beings after birth are absent in the fetal wound. Determination of the cellular and biochemical differences between fetal and postdelivery wound healing offers the promise of improved control over the process of tissue repair. Another promise of fetal wound healing research is the option of in utero repair of defects such as cleft lip and palate. We review what is known at present about fetal wound healing. PMID- 8208571 TI - Methods and materials for wound management. AB - Rumor, myth, and unsubstantiated opinion have guided wound management since our forebearers achieved upright ambulation. The past decade has seen discovery of specific substances and pathways that initiate, control, and terminate healing. The roles of oxygen, nutrition, and growth factors are rapidly revealing themselves to wound healing researchers, and a scientific basis for wound management is emerging. Although the healing process still harbors much mystery, we know enough to improve our methods of wound management. We can now pick from a variety of tools for surgical incision. Scientific studies help in the choice of sutures, needles, and needle holders, as well as alternative closure methods and materials. Natural and synthetic tissue adhesives vie with staples and tapes for use in wound repair. Dressing materials may be active, passive, selectively interactive, or inert. Wound management can be changed to meet changing wound needs, with dressings as diverse as hydrocolloids, silicone gels, and amino acids. We have new ways of improving hypertrophic scarring and practical hopes for its prevention. This article offers a summary of currently available methods and materials for wound management, along with the scientific information that supports and guides their use. PMID- 8208572 TI - Effects of nutrition on wound healing. AB - Optimal wound healing and its close relationship to a patient's positive nutritional balance is well known. For years, physicians have attempted to improve the metabolic status of patients after surgery or trauma. Currently, major emphasis is placed on perioperative nutritional status and its effect on postoperative wound healing. The intricacies of metabolism and healing are areas of current active research, in an effort to advance the quality of patient care. For the head and neck surgeon, wound healing is of paramount concern in areas of tumor extirpation, head and neck reconstruction, and maximization of postoperative functional recovery. To better explain why adequate nutrition is important in postoperative wound healing, we will provide a brief synopsis of nutrition and its relationship to wound healing. PMID- 8208574 TI - The future of wound healing in otolaryngology-head and neck surgery. AB - The future of wound healing progress lies in the support of research being performed at this very moment. In basic science and clinical laboratories all across the nation, there are investigative studies underway, which have as their purpose, the ultimate improvement of wound healing capabilities of the human body in both soft and hard tissues. PMID- 8208573 TI - Growth factors and wound healing in otolaryngology. AB - An immense amount of knowledge has been gained over the last decade in the realm of polypeptide growth factors. Only recently has this new information made an impact in otolaryngology. This article is a brief overview of peptide growth factors in relation to wound healing and otolaryngology. PMID- 8208575 TI - Progressive sensorineural hearing loss in children. PMID- 8208576 TI - Thyroglossal duct cyst in the mouth floor: an unusual location. PMID- 8208577 TI - Atlantoaxial subluxation after typanomastoidectomy in a child with trisomy 21. PMID- 8208578 TI - Oncocytoma of the parotid gland presenting with nerve paralysis. PMID- 8208579 TI - Granulocytic sarcoma of the mandible. PMID- 8208580 TI - Tuberculosis of the cervical spine. PMID- 8208581 TI - Clinical ototoxicity of topical antibiotic drops. PMID- 8208582 TI - Applying the endoscopic stapler in excision of Zenker's diverticulum: a solution for two intraoperative problems. PMID- 8208583 TI - Squamous papilloma of the nasal vestibule. PMID- 8208584 TI - From the National Institute on Deafness and other Communication Disorders. PMID- 8208585 TI - Identification of Babesia bigemina infected erythrocyte surface antigens containing epitopes conserved among strains. AB - The presence of previously uncharacterized antigens (new antigens) on the surface of intact erythrocytes infected with three strains of Babesia bigemina from Kenya and one each from Puerto Rico, Mexico, St. Croix, and Texcoco-Mexico was demonstrated by indirect immunofluorescent antibody (IFA) reactions. These antigens were not strain specific because antibodies in bovine immune serum to either the Mexico or Kenya isolates reacted with all seven strains tested. Homologous and heterologous immune serum antibodies bound a maximum of 83% and 55%, respectively, of intact erythrocytes infected with the Kenya-Ngong strain but not uninfected erythrocytes. Both sera caused agglutination of only infected erythrocytes. Antibodies eluted from the surface of glutaraldehyde (0.25%) fixed infected erythrocytes had IFA reaction patterns among strains similar to those of immune sera before elution. Eluted antibodies were used to determine if these antigens were protein and encoded by B. bigemina. Eluted antibodies bound seven parasite-encoded proteins of 240, 220, 66, 62, 58, 52 and 38 kDa in an erythrocyte surface-specific immunoprecipitation reaction of 35S-methionine labelled proteins. It was concluded that the surface of B. bigemina infected erythrocytes had parasite-encoded proteins and that these proteins had surface exposed epitopes that were conserved among the seven strains examined which were from two continents. PMID- 8208586 TI - Expulsion of Hymenolepis nana from mice with congenital deficiencies of IgE production or of mast cell development. AB - The roles of IgE and mast cells on expulsion of adult Hymenolepis nana from the intestine were examined in mice. IgE-dependency was determined by comparing congenitally IgE-deficient SJA/9 and IgE-producing SJL/J mice infected with 50 H. nana eggs. Anti-H. nana IgE antibody was detected at three weeks post infection (p.i.) in SJL but not in SJA mice. The number of adult worms in the intestines of SJA and of SJL mice were similar at two weeks, but significantly more were found in SJA mice at three weeks p.i. Treatment of mice with anti-epsilon antibody also resulted in an increased worm burden at three weeks, suggesting participation of IgE in expulsion of H. nana. Intestinal mastocytosis was induced by infection regardless of the IgE status of the mice. Mast cell-dependency was tested in mast cell-deficient W/Wv and in normal littermate +/+ mice infected with 100 H. nana eggs. Anti-H. nana antibody was detected in both groups of mice at three weeks p.i. Worm expulsion seemed to be mast cell dependent because expulsion was less complete in W/Wv mice at three weeks p.i. Peripheral blood eosinophilia was comparable at three weeks p.i. in both IgE and mast cell sufficient and deficient mice. These results suggest that IgE and mast cells participate in the expulsion of H. nana adults from intestine in mice. PMID- 8208588 TI - An analysis of the humoral immune response of dogs following vaccination with irradiated infective larvae of Dirofilaria immitis. AB - In this study, dogs were immunized with irradiated L3 larvae of Dirofilaria immitis. Following challenge with non-irradiated L3, vaccinated dogs had an average of 71% fewer adult worms compared to non-vaccinated animals. A comparative analysis of eosinophil and antibody responses of these two groups of dogs is presented. Vaccinated dogs preferentially recognized several larval (14, 20, 30, 34, 39 kDa), adult worm (20 kDa) and microfilarial (36, 38, 71, 84 kDa) antigens. To characterize these antigens, the extent of glycosylation was assessed. The data suggest that an earlier response to these antigens may be important in the protection induced in dogs by administration of irradiated L3 of D. immitis. PMID- 8208587 TI - Hepatic recruitment of mast cells occurs in rats but not mice infected with Schistosoma mansoni. AB - The pathogenesis of infection with Schistosoma mansoni in rats is distinct from that in mice. Rats are non-permissive hosts and infection is terminated in the liver before egg laying commences whereas the parasites completes its life cycle in mice. Comparison of the mast cell responses in the two species reveals that a pronounced hepatic mastocytosis occurs in the rat and this is concomitant with the demise of the parasite. The majority of recruited hepatic mast cells contain the highly soluble granule chymase, rat mast cell protease-II, which is released systemically into blood during the period of parasite elimination. In contrast, very few mast cells are found in livers of parasitized mice and none contain the soluble granule chymase mouse mast cell protease-1. However, during egg deposition in the gut, an intraepithelial mastocytosis occurs in parasitized mice. These intraepithelial cells are typical mucosal mast cells as determined by their content of mouse mast cell protease-1. Recruitment of mucosal mast cells occurs in the intestinal lamina propria of infected rats soon after the parasites migrate to the liver. These findings suggest that mast cells of the mucosal phenotype are involved in the pathogenesis of the hepatic response to infection in the rat but that, in the mouse, mucosal mastocytosis is associated with intestinal sensitization by egg antigens. PMID- 8208589 TI - Detection of antibodies in sera from Chagas' disease patients using a Trypanosoma cruzi immunodominant recombinant antigen. AB - A Trypanosoma cruzi DNA fragment encoding an immunodominant repetitive antigen (H49) was subcloned into a protein purification and expressed system. Purified H49 peptide reacted specifically in an enzyme-linked immunosorbent assay (ELISA) with sera from T. cruzi-infected patients, but not with sera from patients with other parasitic diseases such as leishmaniasis and T. rangeli-infection. The H49 recombinant ELISA was able to detect specific antibodies in 84% of chronic chagasic serum samples tested. One of the major advantage of the recombinant ELISA for serodiagnosis of chronic Chagas' disease resides in its high specificity (100%). Our data suggest that recombinant peptides could provide a practical basis for specific diagnosis tests for Chagas' disease. PMID- 8208590 TI - Evaluation of the interrupter technique for the use of assessing airway obstruction in children. AB - The purpose of this study was to determine if the interrupter technique, a noninvasive method for measuring airflow resistance, could be used to assess airway obstruction in children. In 107 children (74 with asthma, 12 with cystic fibrosis, and 21 without lung disease) conductance (mostly of airways) measured with the interrupter technique (Gint) was correlated with both forced expiratory volume in 1 second (FEV1) and the forced expired flow rate between 25% and 75% of vital capacity (FEF25-75). In addition, 17 children with significant airway obstruction due to asthma also had airway resistance measured by body plethysmography (R(aw)) before and after treatment. Resistance and conductance measurements made with the interrupter technique were subdivided into inspiratory (Rint-insp, Gint-insp) and expiratory (Rint-exp, Gint-exp) values. In the 107 children, a high degree of linear correlation was found between Gint and FEV1; for Gint-exp, r = 0.77 (P < 0.001), and for Gint-insp, r = 0.76 (P < 0.001). There was also good linear correlation between Gint and FEF25-75; for Gint-exp, r = 0.70 (P < 0.001), and for Gint-insp, r = 0.67 (P < 0.001). In the 17 asthmatic children who were tested before and after treatment of their airway obstruction, Rint correlated highly with R(aw); for Rint-exp, r = 0.91 (P < 0.001), and for Rint-insp, r = 0.83 (P < 0.001). The pre- to post-treatment changes in Rint and R(aw) were similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208591 TI - Pulmonary mechanics during respiratory distress syndrome in the prediction of outcome and differentiation of mild and severe bronchopulmonary dysplasia. AB - Pulmonary mechanics was prospectively and longitudinally studied in a cohort of 58 infants who suffered from respiratory distress syndrome. The aim was to determine if early compliance and resistance measurements had additional value to simple clinical variables in predicting poor outcome ie nonsurvival or severe bronchopulmonary dysplasia (BPD) at 28 days. Second, we wanted to determine whether and when the recently described type 1 (mild) BPD and type 2 (severe) BPD could be differentiated by means of lung function tests. In a logistic model, neither lung compliance nor pulmonary resistance at days 1 and 4 of life were selected as predictive variables. On the other hand, gestational age and the ventilatory index no. 1 (ventilator frequency x maximal inspiratory pressure) on day 3 were the best early predictors of poor outcome. Type 2 BPD was characterized by a lower lung compliance and a higher pulmonary resistance than type 1 BPD, although the differences were only significant at 28 days. In conclusion, pulmonary function tests were not helpful in the early prediction of poor outcome at 28 days. They might, however, be of value in the follow-up of BPD patients after 28 days. PMID- 8208592 TI - Are tidal breathing indices useful in infant bronchial challenge tests? AB - Tidal breathing indices have been used to assess histamine-induced airway obstruction in adults and children. The aim of this study was to see whether they could be used to assess histamine challenge in infants. Tidal flow during quiet breathing was measured using a face mask and pneumotachograph and maximum flow at functional residual capacity (VmaxFRC) was measured from partial forced expirations in 18 sleeping, sedated infants who responded to histamine challenge and in 18 nonresponders. The tidal indices calculated were inspiratory and expiratory time (ti and te), tidal peak expiratory flow (PEF), mean tidal expiratory flow rate (VT/te) and the expiratory time constant of the respiratory system (trs). The time to maximal expiration divided by expiratory time (tme/te) and 2 revised forms of this index (tme(a)/te and tme(b)/te) were also calculated. Recordings of tme(a) and tme(b) were taken at 95% of peak tidal expiratory flow, before and after the peak, respectively. In nonresponders, there was an insignificant mean rise in VmaxFRC of 11.8% but no change in any tidal index. In responders, the mean percentage fall in VmaxFRC was 43.3% (range, -31 to -81%); trs fell from 0.61 s to 0.51 s (P < 0.05) and breathing frequency and mean tidal expiratory flow rate increased from 34.0 to 37.5 min-1 (P < 0.01) and from 66.6 to 72.6 mL.s-1 (P < 0.05), respectively, suggesting that infants had adopted a strategy of active expiration in response to bronchial challenge. There was no change either in tme/te or in the revised indices after challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208593 TI - Ventilatory pump failure in premature newborns. AB - OBJECTIVE: To determine the prevalence of ventilatory pump failure in premature (< 34 weeks gestation) infants. DESIGN: Prospective clinical evaluation of all neonatal intensive care unit (NICU) admissions over a 12 month period in a large, university affiliated hospital. SUBJECTS: A series of 421 consecutive inborn premature infant admissions to the NICU. METHODS: Infants were followed for signs and symptoms of respiratory distress and monitored closely for evidence of respiratory failure requiring intubation and assisted ventilation. The indications for intubation and assisted ventilation were reviewed, and three such indications were considered clear manifestations of ventilatory pump failure, that is, delivery room resuscitation with CXR negative for evidence of parenchymal lung disease [DR/CXR-], hypercapnia (PaCO2 > 55 torr) [increases CO2], and apnea. RESULTS: A total of 192 premature infants (47% of study sample) required intubation and assisted ventilation. Failure of the ventilatory pump to sustain ventilation (DR/CXR-, increases CO2, apnea) accounted for 70 of these 192 (36%) premature infants. CONCLUSIONS: Ventilatory pump failure is a common clinical phenomenon in premature infants. Intensified research on the mechanisms and treatment of ventilatory pump failure might benefit a significant number of such newborns. PMID- 8208594 TI - Expression of retinoic acid receptor genes in fetal and newborn rat lung. AB - Lung differentiation and development are affected by vitamin A and its metabolites. One mechanism through which retinoids might exert their effects is through nuclear retinoic acid receptors (RAR). The gene expression profile of the RAR family (alpha, beta, gamma) has previously been determined in both the developing mouse embryo to 14.5 days gestation, and in the adult lung. The purpose of this study was to determine the expression of the RAR genes during the period of gestation that results in the formation of the saccular lung stage. Total RNA was extracted from fetal lungs of Sprague-Dawley rats at gestational days 17, 19, 20, 21, and 22, and from 12-hour-old newborns for Northern hybridization. Two transcripts of RAR alpha mRNA (3.7 and 2.7 kb) were found at each time point. At day 17, the 2.7 kb RAR alpha mRNA was increased two-fold or more than at any other time studied. At days 19-22 the levels of the 3.7 kb RAR alpha species were also lower than day 17 and newborn levels. One RAR beta mRNA transcript (3.4 kb), present at all time points, was significantly higher in the newborn than on days 17-22. Expression of RAR gamma mRNA could only be demonstrated by reverse transcriptase-polymerase chain reaction. We speculate that the higher RAR alpha species at day 17 indicates a role for RAR alpha in the maintenance of the columnar epithelial cells of the glandular phase of lung development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208595 TI - Radiographic lung disease and response of persistent pulmonary hypertension to mean airway pressure and alkalosis. AB - Persistent pulmonary hypertension of the newborn (PPHN) is associated with multiple cardiopulmonary diseases. Therapy often includes hyperventilation/alkalosis despite little evidence as to its efficacy in diverse conditions. To determine (1) if part of the improvement of arterial oxygen tension (PaO2) attributed to alkalosis is actually related to increased mean airway pressure (P(aw)) and (2) if the presence of radiographic pulmonary disease predicts the response to alkalosis or mean airway pressure, we reviewed records of 19 newborns with well-documented PPHN. Arterial blood gases and corresponding ventilator settings were recorded during the first day of life. To adjust for lower FiO2, corrected PaO2 (cPaO2) was calculated when the FiO2 < 1.0, such that cPaO2 = calculated arterial/alveolar oxygen ratio x (713 - PaCO2/0.8). Regression equations were obtained and mean slopes of these were compared for P(aw) vs. cPaO2, and pH vs. cPaO2 by one group t-tests (with assumed population slope of zero). There was no correlation between P(aw) and cPaO2 (mean slope +/- SD = -8.4 +/- 30.8, P = 0.25), but there was a moderate correlation between pH and cPaO2 (mean slope = 333.1 +/- 480.5, P = 0.007). Patients were then classified by chest radiographs as having severe or minimal/no lung disease. Relationships of P(aw) and pH to cPaO2 were then re-examined. No correlation was present between P(aw) and cPaO2 in 11 patients with PPHN and severe radiographic disease (mean slope = 7.4 +/- 26.9, P = 0.38) or in eight patients with PPHN and minimal/no lung disease (mean slope = -9.8 +/- 37.5, P = 0.48).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208596 TI - Cardiorespiratory and stress hormone responses during first dose surfactant administration in neonates with RDS. AB - Our hypothesis was that surfactant instilled into the trachea, followed by body positioning maneuvers utilized to enhance drug distribution, could alter hemodynamic function and stimulate the release of catecholamines. We conducted a prospective randomized study designed to compare the immediate physiologic effects of the first dose of Exosurf Neonatal (5 mL/kg; n = 16) or Survanta (4 mL/kg; n = 18), when surfactant administration was standardized with strict adherence to drug company protocol. Physiologic variables were monitored continuously. Arterial blood gases (ABG) and plasma catecholamine concentrations were measured before, and 5 minutes after, surfactant administration. Both surfactants had an immediate effect on arterial oxygen saturation (SaO2), partial pressure of oxygen in arterial blood (PaO2), and oxygen index (OI). The improvement in oxygenation after surfactant therapy was similar in both groups. There was no significant difference in the mean umbilical arterial blood pressure (ABP) following surfactant therapy in both groups. High concentrations of plasma norepinephrine (reflecting activity of the sympathetic nerves) and epinephrine (a measure of secretion from the adrenal medulla) indicate that preterm infants with respiratory distress syndrome (RDS) prior to treatment mount a substantial stress response. The currently recommended techniques for instillation of surfactant appear not to trigger a significant further surge of plasma catecholamines or to acutely change mean ABP. Alternatively, it may be possible that the lack of response was because catecholamine release was already maximal. PMID- 8208597 TI - Influence of duration of occlusion time on respiratory mechanics measured with the single-breath technique in infants. AB - To determine the effect of the length of end-inspiratory occlusion on the values of respiratory system compliance (Crs) and resistance (Rrs) calculated from the single-breath technique, 6 infants with cystic fibrosis were studied. End inspiratory occlusions lasted between 0.3 and 1.2 seconds, and between 8 and 32 separate occlusions were made in each infant. Examination of the individual data showed a systematic tendency for Crs to decrease as the length of the airway occlusion increased, with statistical significance reached in two subjects. Using a random effects model, it was demonstrated that there was a decrease of 0.15 mL/cmH2O in Crs for each 0.1 s increase in occlusion time. The influence of length of plateau time for Crs was similar to that of total occlusion time. No such tendency was seen for Rrs. These data reinforce the current emphasis on greater standardization in the methodologies used for infant lung function testing and for more fully reporting methodological details. PMID- 8208598 TI - Pneumotachographic nitrogen washout method for measurement of the volume of trapped gas in the lungs. AB - A computerized pneumotachometric multiple breath N2-washout method for assessment of the volume of trapped gas in the lungs (VTGN2) is presented. The VTGN2 is measured as the volume of air mobilized from nonventilated lung spaces by five maximal breaths after a washout performed until the end-tidal nitrogen fraction is 0.02. The method demonstrated a good instrumental precision and the reproducibility of VTGN2 recordings in normal subjects was equal to that achieved with a previous VTGN2 method based on gas collection in bags. It was confirmed that gas trapping occurs in normal children during tidal breathing at functional residual capacity. In normal subjects VTGN2 was directly related to lung size. In 69 healthy children and adolescents VTGN2 showed a good correlation with vital capacity (r = 0.85; P < 0.001), of which it comprised 1.7 +/- 0.4% (mean +/- SD). Patients with bronchial asthma or cystic fibrosis investigated had pathological gas trapping with only a few exceptions; in several cases despite normal results at forced expiratory spirometry. The relative response of VTGN2 (reflecting peripheral airway obstruction) and forced expiratory volume in one second (FEV1) (reflecting conditions in central airways) to beta 2-agonist inhalation among the patients with asthma was variable, indicating that bronchial obstruction is not uniformly distributed along the bronchial tree. Measurements of VTGN2 can be easily performed in children from 7 years of age with the method presented. The computerized VTGN2 method facilitates work and saves time for the operator and provides instant test results. VTGN2 appears to be a sensitive indicator of peripheral bronchial obstruction, giving supplemental information to standard spirometry. PMID- 8208599 TI - Pulmonary vasculitis with hemorrhage in anaphylactoid purpura. AB - We report a 14-year-old female with anaphylactoid purpura (AP) who developed pulmonary hemorrhage with acute vasculitis on lung biopsy. She improved with pulse methylprednisolone, daily prednisone and ventilatory assistance. Pulmonary vasculitis is a rare but serious manifestation of AP. PMID- 8208600 TI - The American Pediatric Society and The Society for Pediatric Research annual meeting. Seattle, Washington. May 2-5, 1994. Abstracts. PMID- 8208602 TI - Preparation of oligodeoxyribonucleoside phosphorodithioates by a triester method. AB - A method to prepare thymidine phosphorodithioate dimers (ref. 1) has been extended to allow the preparation of oligo-2'-deoxyribonucleotide phosphorodithioates containing all four bases. The method is suitable for large scale synthesis and gives phosphorodithioates without phosphorothioate impurities (31P nmr, detection limit 0.5 to 1%). Oligonucleotides up to octamers which contain -0-(PS2-)-0- linkages at all positions have been prepared by block synthesis in solution. The phosphorodithioate linkage is introduced by the reaction of a 5'-O, N-protected nucleoside (or oligonucleotide) with a dithiophosphorylating agent RSP(S)(ODhbt)2, R = 2,4-dichlorobenzyl, Dhbt = 3,4 dihydro-4-oxo-benzotriazin-3-yl, followed by coupling of the product to a 3'-O,N protected nucleoside (or oligonucleotide). This method gives pure protected oligodeoxyribonucleoside phosphorodithioates, and phosphorothioate linkages are only introduced if contact with conc. aqueous ammonia during or after deblocking is unduly prolonged. PMID- 8208601 TI - Conservation of sequence in recombination signal sequence spacers. AB - The variable domains of immunoglobulins and T cell receptors are assembled through the somatic, site specific recombination of multiple germline segments (V, D, and J segments) or V(D)J rearrangement. The recombination signal sequence (RSS) is necessary and sufficient for cell type specific targeting of the V(D)J rearrangement machinery to these germline segments. Previously, the RSS has been described as possessing both a conserved heptamer and a conserved nonamer motif. The heptamer and nonamer motifs are separated by a 'spacer' that was not thought to possess significant sequence conservation, however the length of the spacer could be either 12 +/- 1 bp or 23 +/- 1 bp long. In this report we have assembled and analyzed an extensive data base of published RSS. We have derived, through extensive consensus comparison, a more detailed description of the RSS than has previously been reported. Our analysis indicates that RSS spacers possess significant conservation of sequence, and that the conserved sequence in 12 bp spacers is similar to the conserved sequence in the first half of 23 bp spacers. PMID- 8208603 TI - Definition of a core region of RAG-2 that is functional in V(D)J recombination. AB - The products of the RAG-1 and RAG-2 genes cooperate to allow V(D)J recombination in lymphoid and non-lymphoid cells. As one step toward understanding the role of RAG-2, we have constructed mutated RAG-2 genes and examined their ability to support recombination of plasmid substrates in a fibroblast cell line. The mutations define essential and dispensable parts of the RAG-2 gene. Mutations in the N-terminal part eliminate almost all activity. In the central region of the protein, some but not all local alterations still allow recombination. On the other hand, proteins with large deletions from the C-terminal end, including one truncated by 25%, still retain activity, even though this part of the protein is highly conserved between species. Similar results were obtained with substrates that retain either a signal joint or a coding joint, or perform an inversion. Thus all basic features of V(D)J joining are retained in a RAG-2 protein with only the first 75% of the sequence. PMID- 8208604 TI - Analysis of regions of RAG-2 important for V(D)J recombination. AB - The recombinase activating genes RAG-1 and RAG-2 operate together to activate V(D)J recombination, and thus play an essential role in the generation of immune system diversity. As a first step in understanding the function of the RAG-2 protein, we have tested a series of deletion and insertion mutations for their ability to induce V(D)J joining of a variety of model substrates. Mutants were assayed for their ability to induce deletional and inversional V(D)J joining, thereby testing their proficiency at forming both signal and coding joints, and, in some cases, for their ability to carry out recombination of both extrachromosomal and integrated recombination substrates. All these reactions were affected similarly by any one mutation. Although the RAG-2 protein shows extensive evolutionary conservation across its length, we found that the carboxy terminal portion of RAG-2, including an acidic region, is dispensable for all forms of recombination tested. In contrast, all mutations we created in the N terminal region severely decreased recombination. Thus, the core active region required for V(D)J recombination is confined to the first three-quarters of the RAG-2 protein. PMID- 8208605 TI - Two human homologues of Saccharomyces cerevisiae SWI2/SNF2 and Drosophila brahma are transcriptional coactivators cooperating with the estrogen receptor and the retinoic acid receptor. AB - A set of genes (SWI1, SWI2/SNF2, SWI3, SNF5 and SNF6) in Saccharomyces cerevisiae are required for transcription of a variety of yeast genes. It was recently reported that the mammalian glucocorticoid receptor failed to activate transcription when transiently expressed in swi1-, swi2- or swi3- yeast strains. We report here that two highly related human cDNAs, hSNF2 alpha and -beta, encode amino acid sequences homologous to both the yeast SWI2/SNF2 and the Drosophila brahma. Similar to their yeast and Drosophila counterparts, both human cDNAs contain helicase motifs, a bromodomain, a highly charged C-terminal sequence and an N-terminal sequence rich in proline, glutamine and glycine. Tissue distribution of the mRNAs varied slightly. Transcriptional activation by the estrogen receptor and the retinoic acid receptor was enhanced by co-expression of either hSNF2 cDNA. No enhancement was observed for promoters which do not respond to nuclear receptors. We suggest that global transcriptional coactivators equivalent to the yeast SWI/SNF complex exist in mammalian cells. PMID- 8208606 TI - The tryptophan repressor sequence is highly conserved among the Enterobacteriaceae. AB - Tryptophan biosynthesis in Escherichia coli is regulated by the product of the trpR gene, the tryptophan (Trp) repressor. Trp aporepressor binds the corepressor, L-tryptophan, to form a holorepressor complex, which binds trp operator DNA tightly, and inhibits transcription of the tryptophan biosynthetic operon. The conservation of trp operator sequences among enteric Gram-negative bacteria suggests that trpR genes from other bacterial species can be cloned by complementation in E. coli. To clone trpR homologues, a deletion of the E. coli trpR gene, delta trpR504, was made on a plasmid by site-directed mutagenesis, then crossed onto the E. coli genome. Plasmid clones of the trpR genes of Enterobacter aerogenes and Enterobacter cloacae were isolated by complementation of the delta trpR504 allele, scored as the ability to repress beta-galactosidase synthesis from a prophage-borne trpE-lacZ gene fusion. The predicted amino acid sequences of four enteric TrpR proteins show differences, clustered on the backside of the folded repressor, opposite the DNA-binding helix-turn-helix substructures. These differences are predicted to have little effect on the interactions of the aporepressor with tryptophan, holorepressor with operator DNA, or tandemly bound holorepressor dimers with one another. Although there is some variation observed at the dimer interface, interactions predicted to stabilize the interface are conserved. The phylogenetic relationships revealed by the TrpR amino acid sequence alignment agree with the results of others. PMID- 8208607 TI - Creation of a deletion series of mouse YACs covering a 500 kb region around Xist. AB - Two mouse YACs, PA-2 and PA-3, contain the Xist gene and are 460 kb and 3.3 Mb long respectively. While PA-2 is non-chimeric, PA-3 contains a substantial proportion of non-contiguous DNA. As a prerequisite to functional studies of the role of this region in X inactivation, we have created a deletion series of YACs that are spaced at approximately 50 kb intervals and were able to eliminate the unwanted chimeric sequences in YAC PA-3. For this purpose, we have constructed mouse B1 fragmentation vectors based on those described for human Alu fragmentation. Having created this series of YAC deletion derivatives, we were able to eliminate efficiently the 10-15% aberrant YACs that arise during the course of a fragmentation experiment by assessing their marker content. The overlap and the opposite orientation of the two YAC inserts permitted the creation of deletions on both sides of the 500 kb region around Xist. The use of this series of YACs in a biological assay will help us define the extent of the sequences necessary to bring about X chromosome inactivation. PMID- 8208608 TI - Promoter elements and transcriptional control of the chicken tropomyosin gene [corrected]. AB - The chicken beta tropomyosin (beta TM) gene has two alternative transcription start sites (sk and nmCAP sites) which are used in muscle or non muscle tissues respectively. In order to understand the mechanisms involved in the tissue specific and developmentally-regulated expression of the beta TM gene, we have analyzed the 5' regions associated with each CAP site. Truncated regions 5' to the nmCAP site were inserted upstream to the bacterial chloramphenicol acetyltransferase (CAT) reporter gene and these constructs were transfected into avian myogenic and non myogenic cells. The maximum transcription is driven by the CAT construct (-168/ + 216 nt) in all cell types. Previous deletion analysis of the region 5' to the beta TMskCAP site has indicated that 805 nt confer myotube specific transcription. In this work, we characterized an enhancer element (-201/ 68 nt) which contains an E box (-177), a variant CArG box (-104) and a stretch of 7Cs (-147). Mutation of any of these motifs results in a decrease of the myotube specific transcriptional activity. Electrophoretic mobility shift assays indicate that these cis-acting sequences specifically bind nuclear proteins. This enhancer functions in an orientation-dependent manner. PMID- 8208609 TI - Identification of the rat xanthine dehydrogenase/oxidase promoter. AB - Inflammation and ischemia--reperfusion tissue injury are important pathophysiologic processes with a wide spectrum of clinical presentations; the enzyme xanthine dehydrogenase/oxidase (XDH/XO) is thought to play a key role in ischemia--reperfusion injury. Recent studies have shown the transcriptional regulation of XDH/XO by cytokines (Dupont et al., 1992, J. Clin. Invest. 89, 197 202). In the present study, the 5' structure of the XDH/XO gene and characterization of its promoter are undertaken providing an initial step to further elucidate the regulatory mechanism(s) of this enzyme. XDH/XO cDNA from rat bone marrow macrophage has been isolated and used to screen a rat genomic library in order to identify and characterize the promoter of the XDH/XO gene. By Southern analysis, XDH/XO was found to be a single copy gene in the rat genome. Primer extension, RNase protection, and anchor-PCR studies indicate the presence of multiple start sites within a 65 bp window located some 20-85 bp upstream of the translation initiator (ATG). Functional studies of the sequences up to 116 nt upstream of the translational start site, which encompasses the several transcriptional start sites, indicate that this region is sufficient to drive the expression of a luciferase reporter gene and is presumed to represent the promoter. Neither a TATA box nor a GC-rich region are present in close proximity to any of the transcriptional start sites; however, sequences with homology to known initiator elements are found within this 116 bp fragment. Several possible regulatory elements, including a NF-IL6 motif, are also located upstream of the transcriptional start site. This study represents the first description of the XDH/XO promoter from a vertebrate system. PMID- 8208610 TI - The beta recombinase from the Streptococcal plasmid pSM 19035 represses its own transcription by holding the RNA polymerase at the promoter region. AB - The beta protein encoded by the Streptococcus pyogenes plasmid pSM19035 is a site specific recombinase involved in both resolution of plasmid multimers into monomers and DNA inversion. It has been proposed that the DNA region to which the beta recombinase binds to mediate recombination includes a promoter from which orf alpha and the beta gene are transcribed. We have determined the sites at which transcription of the orf alpha and the beta gene initiates in vitro and we have demonstrated that highly purified beta recombinase acts as a repressor of its own synthesis. The promoters are located within the beta recombinase binding site, which we have defined previously. The binding of the beta recombinase to its target site does not seem to exclude RNA polymerase from the promoter, despite the overlapping of their binding sites. Therefore, it is likely that the beta recombinase does not repress transcription by a mere steric hindrance on RNA polymerase binding. PMID- 8208611 TI - Highly efficient DNA synthesis in isolated mitochondria from rat liver. AB - We have developed a highly efficient DNA-synthesizing system with isolated intact rat liver mitochondria. The ATP requirements for this in organello DNA synthesis are provided by endogenous synthesis in the presence of exogenous ADP and an oxidizable substrate. In this system, mitochondrial DNA synthesis strikingly proceeds at a constant rate for about 5 h at 37 degrees C. Gel electrophoresis, hybridization and restriction enzyme analyses show that intact mitochondria synthesize nucleic acids with a size of 16.5 kb, that correspond to mitochondrial DNA, and that both DNA strands are replicated. This in organello DNA synthesis requires the supply of dNTPs and decreases at high ADP concentration in the incubation medium. PMID- 8208612 TI - Molecular cloning of a human small intestinal apolipoprotein B mRNA editing protein. AB - Mammalian small intestinal apolipoprotein B (apo B) mRNA undergoes posttranscriptional cytidine deamination with the production of an in frame stop codon and the translation of apo B48. We have isolated a cDNA from human jejunum which mediates in vitro editing of a synthetic apo B RNA template upon complementation with chicken intestinal S100 extracts. The cDNA specifies a 236 residue protein which is 69% identical to the apo B mRNA editing protein (REPR) cloned from rat small intestine [Teng, B., Burant, C. F. and Davidson, N. O. (1993) Science 260, 1816-1819] and which, by analogy, is referred to as HEPR. HEPR does not contain the carboxyl-terminus leucine zipper motif identified in REPR but contains consensus phosphorylation sites as well as the conserved histidine and both cysteine residues identified as a Zn2+ binding motif in other cytidine deaminases. The distribution of HEPR mRNA was predominantly confined to the adult small intestine with lower levels detectable by reverse-transcription polymerase chain reaction amplification in the stomach, colon and testis. These differences in the structure and distribution of the human as compared to the rat apo B mRNA editing protein suggest an important evolutionary adaptation in the mechanisms restricting apo B48 production to the small intestine. PMID- 8208613 TI - Hybridization-based affinity partitioning of nucleic acids using PEG-coupled oligonucleotides. AB - Polyethylene glycol (PEG)-coupled oligonucleotides are partitioned in an aqueous two-phase system PEG/dextran. The affinity of the oligonucleotide for the PEG rich phase increases proportionally to the length of the coupled PEG polymer. After hybridization, the PEG-coupled oligonucleotide is able to force a complementary nucleic acid strand into the PEG-rich phase. This property can be used for the sequence-specific isolation of nucleic acids through hybridization based affinity partitioning. The dependence of the partition coefficient in this system on various parameters is described. The application of this principle to multistage chromatographic separations is demonstrated. PMID- 8208614 TI - Murine protein which binds preferentially to oligo-C-rich single-stranded nucleic acids. AB - Two single-stranded nucleic acid binding proteins mCBP and mCTBP were identified by means of their binding to a potential recombination hotspot in LTRs of mouse retro-transposons. Both are nuclear proteins of 35 and 55 kDa respectively. mCBP binds preferentially to oligo dC, mCTBP to oligo dCdT. mCBP was purified and its cDNA was isolated and sequenced. PMID- 8208615 TI - TBP-DNA interactions in the minor groove discriminate between A:T and T:A base pairs. AB - In this report, we test the hypothesis that TBP binds DNA promiscuously due to its manner of recognition of the DNA minor groove. The experiment performed was to select TBP-binding sequences from a pool of random double stranded oligonucleotides. Sixty two clones from this pool were sequenced. Surprisingly, the results show that TBP has a marked preference for stably binding one sequence (TATATAA) over all others, yet only four classes of TATA box were selected. The features of the selected sequences allow definition of a binding consensus for TBP. The DNA binding properties of TBP to the four TATA variants was examined, the results being in accord with the observed selection frequencies. However, the nature of TBP-DNA binding is strongly affected by ionic strength. We infer that recognition of DNA via the minor groove can be highly selective even where A:T and T:A discrimination is required. Models for how this might be accomplished are discussed. PMID- 8208616 TI - Mechanism of mutation on DNA templates containing synthetic abasic sites: study with a double strand vector. AB - Mutagenesis at abasic sites was investigated in E.coli and simian kidney (COS) cells using a duplex shuttle vector containing synthetic analogs of deoxyribose on the phosphodiester backbone. Lesions were positioned on opposite strands of the vector. When the tetrahydrofuranyl analog was used as the abasic site, AT or TA pairs (65-80%) were introduced at the site of the bistrand lesion. Mutagenesis occurred in the absence of SOS induction. Single base deletions (> 80%) dominated the mutational spectra for propanyl and ethanyl analogs of abasic sites lacking a ring structure. For all abasic site analogs, a small proportion of G/C and C/G pairs (6-10%) were observed. dAMP was incorporated predominantly opposite tetrahydrofuranyl sites positioned in the single strand region of a gapped duplex vector. We conclude from these studies that abasic sites positioned in a bistrand configuration are highly mutagenic in E.coli and COS cells. Repair DNA synthesis may be involved in this process. PMID- 8208617 TI - Antisense overlapping open reading frames in genes from bacteria to humans. AB - Long Open Reading Frames (ORFs) in antisense DNA strands have been reported in the literature as being rare events. However, an extensive analysis of the GenBank database revealed that a substantial number of genes from several species contain an in-phase ORF in the antisense strand, that overlaps entirely the coding sequence of the sense strand, or even extends beyond. The findings described in this paper show that this is a frequent, non-random phenomenon, which is primarily dependent on codon usage, and to a lesser extent on gene size and GC content. Examination of the sequence database for several prokaryotic and eukaryotic organisms, demonstrates that coding sequences with in-phase, 100% overlapping antisense ORFs are present in every genome studied so far. PMID- 8208618 TI - Effect of abasic linker substitution on triplex formation, Sp1 binding, and specificity in an oligonucleotide targeted to the human Ha-ras promoter. AB - A region of the human Ha-ras promoter (-8 to -28) which contains two of the three Sp1 binding sites essential for transcriptional activity forms a sequence specific oligonucleotide-directed pur*pur:pyr triple helix. The relative binding of oligonucleotides containing different substitutions, including an abasic propanediol linker, over three potentially destabilizing C:G interruptions in the otherwise poly G:poly C target was examined. DNase I footprint titrations reveal that substitution of the positively charged abasic propanediol linker results in approximately ten fold greater binding than cytosine substitution which in turn provides greater sequence specific binding than substitution of a guanine in the third strand oligonucleotide over the C:G interruptions. Protein binding assays demonstrate that triplex formation by the linker substituted oligomer (HR21Xap) is less effective in inhibiting Sp1 binding than the cytosine substituted oligomer (HR21ap) both to the target sequence as well as an upstream sequence. As an indication of the effect of linker substitution and targeting consensus Sp1 sites on triplex specificity, the relative ability of the Ha-ras promoter targeted oligonucleotides to interact with non-target Sp1 sequences within the Ha ras promoter as well as in the DHFR promoter and HIV-1 LTR was also investigated. At concentrations which afford complete DNase I protection of the target sequence, HR21ap does not bind to the non-target sequences while HR21Xap interacts weakly only at a distal site in the DHFR promoter. Also, HR21ap as well as HR21Xap are specific in their inhibition of Sp1 binding. These results suggest that the propanediol linker is able to skip over interruptions in a target sequence thereby stabilizing triplex but, slightly compromises sequence specificity and the ability to inhibit Sp1 binding to the Ha-ras promoter. PMID- 8208619 TI - PCR template-DNA isolated quickly from monocot and dicot leaves without tissue homogenization. PMID- 8208620 TI - Reproducible DNA fingerprinting with the random amplified polymorphic DNA (RAPD) method. PMID- 8208621 TI - Improved preservation of chromatin structure in ethanol-fixed cells. PMID- 8208622 TI - Detection of prostatic-inhibin-like peptide in the cytoplasm of LNCaP cells, a human prostatic adenocarcinoma cell line. AB - Prostatic inhibin peptide (PIP) is a 94-amino acid peptide involved in various cellular functions. The concentration of this peptide changes with prostatic pathophysiology suggesting a role in various disease conditions; present study was undertaken to investigate the presence of this peptide in two human prostatic cell lines: LNCaP and PC3 cells. The LNCaP cells showed an intense intracellular fluorescence pattern after staining with rabbit-anti-PIP antiserum and FITC conjugated goat antirabbit-IgG, while the PC3 cells did not exhibit any fluorescence. There was no alteration in the concentration of PIP in LNCaP cells with or without supplementation of steroids in culture medium. Immunoblot analysis indicates similarities between PIP from LNCaP cells and that from the human seminal plasma. Thus, present study demonstrates the presence of PIP in a human prostatic cell line, i.e., LNCaP cells. Its intracellular concentration is androgen independent, and has a close similarity with PIP isolated from the human seminal plasma. PMID- 8208623 TI - An experimental model simulating local recurrence and pelvic lymph node metastasis following orthotopic induction of prostate cancer. AB - In order to develop an animal model that more closely simulates the organ environment and metastatic routes of human prostatic cancer, R3327-MatLyLu tumors were induced by orthotopic implantation in the ventral prostatic lobe of Copenhagen rats. This procedure reproducibly resulted in metastatic spread of the intraprostatic tumor to the pelvic and retroperitoneal lymph nodes, and invariably to the lungs. Further, a tumor recurrence model was established using an approach that combined orthotopic tumor implantation and subsequent surgical resection of the primary tumor. When prostatectomy was carried out 4 days or more after induction, tumors recurred locally in all animals. The surgical procedures described may provide an animal model to test the in vivo response to experimental adjuvant treatment protocols for advanced prostate cancer. Immunological studies are now in progress using cytokine gene-modified prostatic tumor cells as cellular antitumor vaccines in orthotopically established R3327 MatLyLu tumors. PMID- 8208624 TI - N-(4-hydroxyphenyl) retinamide induces cell cycle specific growth inhibition in PC3 cells. AB - The synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) has been demonstrated to inhibit the development of primary and metastatic neoplasms in several animal models. In order to investigate the effect of 4-HPR on human prostate adenocarcinoma, we designed a series of in vitro experiments with the PC3 cell line to evaluate effects on proliferation, cell cycle kinetics, and c myc mRNA expression. 4-HPR demonstrated cytotoxicity only at the supraphysiologic concentration of 10.0 microM. However, asynchronously growing cells exposed to 1 microM 4-HPR demonstrated a 51% reduction in proliferation rate, associated with an accumulation of cells in the G0/G1 phase of the cell cycle. PC3 cells synchronized with serum deprivation or aphidicolin exhibited significant decreases in DNA synthesis when treated with 1 microM 4-HPR. Additionally, these cells were found to accumulate in G0/G1 and S phase. Northern blots indicated a significant decrease in c-myc mRNA expression in asynchronously growing cells with continuous administration of 1 microM 4-HPR for 6 days. These data suggest that 4-HPR can inhibit growth of PC3 cells as a consequence of a block in cell cycle transition from G1 to S phase at a concentration of 1 microM, and that this inhibition is associated with a suppression of c-myc gene expression. PMID- 8208626 TI - [Latent virus infections of cells in the immune system]. AB - The article concerns the latent infections of cells of immune system caused by herpesviruses and retroviruses. Molecular basis of latency maintained by Epstein Barr virus in B lymphocytes as well as by human immunodeficiency virus in TCD4 lymphocytes is described. The switch between latency and replication of the viruses and immune surveillance is discussed. PMID- 8208625 TI - DNA analysis by flow cytometry of paraffin embedded core biopsies of the prostate. AB - The majority of literature concerning DNA analysis of prostate cancer involves testing formalin-fixed prostatectomy tissue, fresh or formalin-fixed transurethral resections of the prostate (TURP), or fresh core biopsies. We were interested if flow cytometry could analyze the DNA of formalin-fixed, paraffin embedded, core biopsies separated into normal versus malignant segments. Of the 50 potentially available samples for analysis representing 11 controls of normal core tissue and 39 core biopsies from the 11 patients, one patient had no normal tissue, one core had no malignancy, and three cores had no tissue visibly remaining in the paraffin blocks for analysis. Therefore, of 45 actual samples available for processing, sometimes representing segments as small as 0.2 cm, separate segments containing malignant glands or normal glands were excised from the blocks, and processed separately by the Hedley technique. Forty-four of the 45 available samples produced interpretable DNA histograms as defined by discernible G0/G1 peaks, a calculable cell cycle analysis, and the qualitative appearance of a "smooth" histogram appearance, reflecting sufficient nuclei were analyzed. This is the first report to our knowledge where flow cytometry has successfully been used to analyze paraffin blocks of core biopsies which were, in addition, separated into malignant versus normal enriched segments. PMID- 8208627 TI - [Cytokines, their receptors and inhibitors. Importance in laboratory diagnosis of rheumatoid arthritis]. AB - The present paper reviews the literature on biological activities of human cytokines in homeostasis, as modulated by their secretion, expression of membrane bound and soluble receptors as well as by means of other cytokines and specific inhibitors, respectively. The role of structure and properties of interleukins 1, 2, 6 and their receptors in pathophysiology and laboratory diagnostics of rheumatoid arthritis, is discussed. Methods of quantitative determination of cytokines are described. PMID- 8208629 TI - [Dna damage induced by active oxygen species and its role in the carcinogenesis process]. AB - Oxygen, a necessary element for the life of a cell is also the source of active state of oxygen including free radicals, which can induced damage to cellular DNA. The damage can result in deleterious biological consequences such as the initiation and promotion of cancer. In this paper the characterization of the DNA damage and molecular mechanisms causing this damage is presented. PMID- 8208628 TI - [Biology and therapy of hairy cell leukemia]. AB - In the paper recent advances in etiology and pathogenesis of hairy cell leukaemia (HCL) are reviewed. Role of human T-cell leukaemia virus II (HTLV-II) and Epstein Barr virus as well as benzene and other environmental factors in the etiology of this leukaemia is presented. The new achievements in diagnosis including electron microscopic, cytogenetic and immunologic studies are discussed. A rare variants of HCL are described. The special attention is paid to the modern approach in treatment including alfa-interferon, 2'-deoxycoformycin and 2 chlorodeoxyadenosine. PMID- 8208630 TI - [Renin-angiotensin system and atherosclerosis]. AB - Based upon literature the renin-angiotensin system involvement in the pathogenesis of atherosclerosis has been discussed. Angiotensin II leads to the increased production of growth factors such as PDGF, TGF-beta, FGF and extracellular matrix proteins. There are evidences that angiotensin II stimulates expression of egr-1, c-jun, c-fos and c-myc oncogenes in vascular smooth muscle cells. Proliferation of aortic smooth muscle cells in response to the injury can be reduced by inhibitors of renin-angiotensin system what supports the hypothesis that angiotensin II can contribute to the pathogenesis of atherosclerosis. PMID- 8208631 TI - [Biological function and toxicity of molybdenum]. PMID- 8208632 TI - [New perspective antisense strategies--regulation of protein biosynthesis]. PMID- 8208633 TI - [Molecular basis of mutagenic activity of vinyl chloride]. PMID- 8208634 TI - [Nobel prizes in physiology, medicine and chemistry in 1993]. PMID- 8208635 TI - [Function of protein tyrosine kinases during platelet activation]. PMID- 8208637 TI - [Agrin--structure and role in neuromuscular synapse]. PMID- 8208636 TI - [Structure and function of integrin receptors based on platelet receptor for fibrinogen]. PMID- 8208638 TI - [Cytochrome b/f complex of chloroplast membranes]. PMID- 8208639 TI - [Human gene p53]. PMID- 8208641 TI - ACE inhibition versus calcium antagonism in the treatment of mild to moderate hypertension: a multicentre study. Ireland-Netherlands Lisinopril-Nifedipine Study Group. AB - The efficacy of lisinopril 10-40 mg once daily was compared with that of nifedipine tablets 20-40 mg twice daily in a multicentre double-blind randomized parallel group study of 16 weeks duration involving 127 patients with mild to moderate hypertension. The groups randomized to lisinopril or to nifedipine were not significantly different with respect to any demographic variable. An analysis of the pooled data from all centres demonstrated a significantly greater fall in both lying and standing systolic blood pressure (SBP) on lisinopril than on nifedipine treatment (difference between treatments 7.70 +/- 3.34 mmHg; P = 0.02 and 10.2 +/- 3.30 mmHg; P = 0.003 for lying and standing SBP, respectively). However, this difference may be accounted for by the slightly higher mean SBP in the lisinopril treatment groups compared with the nifedipine group at the end of the placebo run-in period. Both treatments lowered lying and standing diastolic blood pressures (DBP) to the same extent and the response rates to the two treatments were the same. The effects of the two drugs on heart rate were indistinguishable from each other. There were six lisinopril and 12 nifedipine treated patients withdrawn during randomized treatment (P = 0.22). Nineteen per cent of lisinopril patients reported an adverse event compared with 36% of nifedipine patients. The relative risk of an adverse event on lisinopril compared with nifedipine was 0.42 (confidence limits 1.027-0.172) a difference which approached statistical significance (P = 0.0573). Lisinopril produced a greater reduction in both lying and standing SBP than nifedipine and both were associated with equivalent reductions in DBP. Lisinopril may be better tolerate than nifedipine. PMID- 8208640 TI - Microvascular investigations in diabetes mellitus. AB - This paper reviews the current literature concerning the different investigative modalities available to assess the microcirculation in diabetic microangiopathy. The advantages and disadvantages of the different invasive and noninvasive methods available are presented objectively. We have concentrated on the tests that provide a quantitative assessment of the microcirculation, including laser Doppler fluxmetry, capillary microscopy, plethysmography, transcutaneous oximetry and radioactive isotope clearance. Some of the invasive methods described are now being replaced by noninvasive equivalents, providing similar information with less discomfort and risk to the patient. PMID- 8208642 TI - Evaluation of a commercial enzyme-linked immunosorbent assay (ELISA) kit for serological diagnosis of Helicobacter pylori infection in a group of non-ulcer dyspepsia sufferers. AB - Helicobacter pylori infection of the stomach is associated with gastritis and peptic ulceration and may be causative. A noninvasive test for this organism might be useful in managing some patients with dyspepsia without the need for further investigation. We have evaluated a new commercially available serological test (Helico-G ELISA, Porton Cambridge, UK) for this infection to assess its diagnostic accuracy in a retrospective study of 115 patients with non-ulcer dyspepsia. Sixty-three of these patients (55%) were found to have H. pylori infection and gastritis on histology. A sensitivity of 81% and specificity of 90% were obtained. No significant fall in the antibody titres was found in a subgroup of 15 patients who were selected to complete a course of triple therapy despite significant improvement in their dyspepsia score and confirmed eradication of H. pylori organism in 80% of these patients. We conclude that the test has limited value in aiding clinical decision of managing patients with dyspepsia. PMID- 8208643 TI - Patients with atherosclerotic renovascular disease presenting to a renal unit: an audit of outcome. AB - During a 6 year period 60 patients with atherosclerotic renovascular disease were followed by a single renal unit. Angiotensin converting enzyme inhibitors were being taken by 22% of patients at the time of diagnosis of the atherosclerotic renovascular disease. Intervention to revascularize renal tissue by surgery or angioplasty was performed in 32 patients. Revascularization was not undertaken because of unilateral disease, patient preference, poor operative risk or renal size. The mean age for the nonintervention group was 66.9 years and 63.4 years for the intervention group. Peripheral vascular, disease was common in both groups (96% nonintervention group versus 86% intervention group). There was a statistically significant difference in improvement in renal function in the intervention group (34.4% versus 10.7%) in spite of more patients being dialysis dependent in the intervention group (28.1% versus 14.3%). There was no statistically significant difference in survival between the two groups although the trend was for better survival in the group with intervention. Patients presenting with impaired renal function and atherosclerotic renovascular disease can have useful improvement in renal function with revascularization without any detriment to survival. PMID- 8208644 TI - Shigella bacteraemia in adults. AB - Shigella infections are usually restricted to the intestine. There are few reports of Shigella isolated from the blood and most of these are from children, usually in neonates and the malnourished. In the small number of adult cases of Shigella bacteraemia which have been reported, there appears to be an association with underlying disease and immunosuppression including acquired immunodeficiency syndrome. We report three adult cases in which Shigella were isolated from blood. Two of these patients made an uneventful recovery whilst the third died. An underlying cause of immunosuppression was suspected in this patient but unproven. PMID- 8208645 TI - Training the senior house officer: experience within a dermatology unit. PMID- 8208646 TI - Fatal diltiazem overdose: report of four cases and review of the literature. AB - Four fatal cases of diltiazem overdose are described and compared with previously published cases. Clinical sequelae include all grades of heart block, hypotension and ultimately death. Management includes gastric lavage and oral administration of activated charcoal at presentation. Further symptomatic treatment with inotropic agents and temporary cardiac pacing may be required. If these measures are successful, recovery occurs within 36 hours in uncomplicated cases. Toxicological data have been reviewed but currently drug levels can only offer a retrospective analysis of the severity of overdoses. As the use and risk of abuse of diltiazem increases, these reports serve to highlight the possible hazards and to alert physicians to what must be regarded as a dangerous and potentially lethal drug in overdosage. PMID- 8208647 TI - Scrotal deficiency--localized. PMID- 8208648 TI - Reversibility of myocardial dyskinaesia due to severe hypertension. AB - Two cases of acute left ventricular failure associated with severe essential hypertension are presented. On admission echocardiography indicated severe dyskinaesia of all wall segments of the heart. Anti-hypertensive treatment resulted in significant improvement in clinical and echocardiographic findings. PMID- 8208649 TI - A feminizing adrenocortical carcinoma presenting with gynaecomastia. AB - A case is presented in which gynaecomastia was the sole initial presenting symptom of a feminizing adrenocortical carcinoma. This rare pathological lesion is discussed. PMID- 8208650 TI - Hypercalcaemia and multiple osteolytic lesions in childhood acute lymphoblastic leukaemia. AB - A 12 year old boy presenting with hypercalcaemia (calcium 3.25 mmol/l) and osteopaenia with multiple osteolytic lesions was found to have acute lymphoblastic leukaemia without lymph-adenopathy or organomegaly. Hypercalcaemia is a rare feature of acute leukaemia, but the patients previously described all show very similar characteristics, which were highlighted in this patient. These include age (10-20 years), severe osteolytic bone lesions, lymphoblastic leukaemia, and normal white cell count with absent or rare circulating blasts. Parathyroid hormone levels were normal in this patient, and response to induction therapy was good. This case demonstrates that acute lymphoblastic leukaemia may present in an atypical form without peripheral blasts but with hypercalcaemia and gross skeletal changes. PMID- 8208651 TI - Pancreatitis associated with diclofenac. AB - A 34 year old female developed acute pancreatitis after commencing diclofenac for a painful arthropathy. The possible role of prostaglandin inhibition in non steroidal analgesic drug-induced pancreatitis is discussed and the suggestion is made that serum amylase should be measured in patients who develop abdominal pain, following ingestion of non-steroidal anti-inflammatory PMID- 8208652 TI - Intraperitoneal haemorrhage from anterior abdominal wall varices. AB - Patients with oesophageal varices frequently present with gastrointestinal haemorrhage but bleeding from varices at other sites is rare. We present a patient with hepatitis C-induced cirrhosis and partial portal vein occlusion who developed spontaneous haemorrhage from anterior abdominal wall varices into the rectus abdominus muscle and peritoneal cavity. PMID- 8208654 TI - Submucosal lipoma of the colon with intussusception. PMID- 8208653 TI - Gangrene of the anterior abdominal wall after orthotopic liver transplantation: invasive cutaneous candidiasis. AB - Fungal infections following liver transplantation are not uncommon and may be life-threatening. Superficial candidal infections of the bronchus, oesophagus and urinary tract are the most common mode of presentation. Invasive cutaneous and subcutaneous candidiasis is, however, very rare. We report two patients with invasive cutaneous and subcutaneous candidiasis after orthotopic liver transplantation. PMID- 8208655 TI - Electrocardiographic Q-Tc prolongation associated with infusion of intravenous pamidronate disodium. PMID- 8208656 TI - Sublingual captopril in hypertensive urgencies. PMID- 8208657 TI - Primary anaerobic bacterial meningitis caused by Propionibacterium acnes. PMID- 8208658 TI - Syncope caused by ranitidine-induced increase in A-V block. PMID- 8208659 TI - Osteoporotic vertebral collapse in a woman. PMID- 8208660 TI - Peripheral vascular disease. PMID- 8208661 TI - Surgical treatment of intractable pain. PMID- 8208662 TI - Dietary change in arthritis. PMID- 8208663 TI - Hearing loss. PMID- 8208664 TI - Diagnosis and treatment of hoarseness. PMID- 8208665 TI - Treating gout in the presence of cardiac failure. PMID- 8208666 TI - GTP-binding proteins associated with the human placental syncytiotrophoblast plasma membrane. AB - The nature of GTP-binding components associated with isolated human term placental syncytiotrophoblast microvillous plasma membrane vesicles (SPMV) was determined; these are relevant to elucidation of intracellular signal transduction mechanisms. Four proteins were identified, with molecular weights of 29, 27, 23 and 21 kDa, which specifically bound [alpha-32P]GTP in the presence of Mg2+. Studies employing anti-p21c-ras monoclonal antibodies indicated these four GTP-binding components were ras-related and one, the 21 kDa component, may be p21c-ras. In addition, SPMV were also found to express the alpha subunits of three separate G proteins. A 45 kDa SPMV GTP-binding protein was identified as a substrate for Vibrio cholera toxin and was recognized by a rabbit antibody to the alpha subunit of the adenylate cyclase stimulating G protein, Gs. A 41 kDa SPMV GTP-binding protein substrate of Bordetella pertussis toxin was also recognized by rabbit antibodies to the alpha subunits of the adenylate cyclase inhibiting G proteins, Gi-1 and Gi-3. No evidence was found to support the presence of the 21 kDa Gp, a G protein previously associated with membranes prepared from whole placental tissue homogenates. PMID- 8208667 TI - Regulation by interleukin-1 beta of growth and collagenase production by choriocarcinoma cells. AB - Impaired trophoblastic invasion and proliferation have been implicated in the pathogenesis of eclampsia, pre-eclampsia, spontaneous abortions and intra-uterine growth retardation (IUGR). First trimester trophoblast cells (which do not grow in culture) and choriocarcinoma (BeWo) (which grow spontaneously, and are used as a model for proliferating trophoblast) were incubated with interleukin-1 beta (IL 1 beta). BeWo cell growth was decreased dose-dependently by exogenous IL-1 beta at concentrations of 100-1000 pg/ml. This effect was first detected after 24 h of incubation with IL-1 beta, and persisted for up to 96 h of culture. In contrast, trophoblast cells isolated from first trimester placental tissue showed no growth response when stimulated with IL-1 beta. The levels of active interstitial collagenase produced by BeWo cells were increased by IL-1 beta (100-1000 pg/ml), which paralleled the decrease in cell growth. First trimester trophoblast cells produced lower levels of collagenase and this was not affected by incubation of the cells by IL-1 beta. These results indicate that IL-1 beta may regulate placental development, but further development of culture systems for first trimester trophoblast will be needed before this result can be confirmed. PMID- 8208668 TI - Developmental expression of Glut1 glucose transporter and c-fos genes in human placental cells. AB - Glut1, the brain/erythrocyte glucose transporter is one major isoform of the human placenta and displays an age-specific pattern of expression with mRNA levels five-fold higher in first trimester than in term placenta. By contrast, the mRNA level of the insulin-regulatable glucose transporter Glut4 remains at the limit of detection throughout pregnancy indicating a very low expression of this isoform in the placenta. The nuclear proto-oncogenes c-fos and c-myc were also detectable in the human placenta, but c-fos only exhibited an age-specific pattern of expression with levels higher in third trimester than in term placenta. Primary cultures of human trophoblast cells from term placenta were used to further study the expression and regulation of Glut1 and c-fos genes. Fetal calf serum rapidly and transiently (15 to 60 min) stimulated c-fos and Glut1 gene expression suggesting that both genes share similar growth factor controlled pathways. Glucose inhibited Glut1, but not c-fos expression. An eight fold decrease in Glut1 mRNA was observed when glucose concentration in the medium was increased from 0 to 25 mM, whereas c-fos mRNA levels remained very low. These results suggest that in the human placenta, the expression of Glut1 is specifically regulated by glucose concentration. These data demonstrate that (1) Glut1 and c-fos mRNA transcripts are expressed in the human placenta exhibiting an age-specific pattern of expression, (2) In cultured trophoblast cells, both genes are stimulatable by fetal calf serum and in contrast to c-fos, Glut1 is negatively regulated by glucose. This differential regulation of Glut1 and c-fos genes could be relevant to specific metabolic and mitogenic pathways implicated in placental growth and differentiation. PMID- 8208670 TI - Growth and maturation of villi in placentae from well-controlled diabetic women. AB - Placentae from controls and two groups of diabetic women (one White classes A, B, C and the other classes D, F/R) were collected at 37-42 weeks of gestation. Tissue sections were analysed using stereological methods in order to quantify the growth and maturational status of villi. Birth and placental weights were recorded and placentae sampled in a systematic manner. Fields of view on formalin fixed, paraffin-embedded sections were analysed to obtain estimates of volumes, surface areas, lengths and diffusion (harmonic mean) distances. Comparisons were drawn using three-way analyses of variance with group, mode of delivery and sex of newborn as the principal effects. Mean weights were similar in controls and diabetic groups. Diabetic placentae had a more voluminous fetal capillary bed of greater length, diameter and surface area. In addition, the diffusion distances across fetal plasma (erythrocyte to endothelium) were shorter. Stromal diffusion distance and villous diameter were greater in vaginal deliveries. Interaction effects influenced also villous capillarization, capillary volume, capillary diameter, trophoblast thickness and stromal thickness. Our results emphasize the importance of adaptations on the fetal side of the diabetic placenta. They show that changes can affect the placentae of appropriate-for-age as well as large-for age babies and provide no evidence that they increase with the severity and duration of diabetes. PMID- 8208669 TI - Placental water content and distribution. AB - The percentage of total placental water (%H2O(T)), maternal (%MBV) and fetal (%FBV) blood volumes, non-vascular extracellular (%EW) and intracellular (%IW) water, and villous histology were studied in placentas from 12 normal term pregnancies after a normal vaginal delivery, 19 caesarean sections at term after a normal pregnancy and history of a previous caesarean section and 47 caesarean sections at term or preterm due to pregnancy complications. Values were derived from change in placental dry weight, maternal and fetal haemoglobin content and 51CrEDTA space after incubation of placental fragments. Normal ranges (mean +/- SD) after term vaginal delivery were: H2O(T) 83.9 +/- 0.2%, MBV 10.9 +/- 0.2%, FBV 7.4 +/- 0.9%, EW 57.3 +/- 1.3% and IW 11.2 +/- 0.6%. %H2O(T) was higher after caesarean section; other measurements were not affected. There were no differences between placentas after 33-37 and after 38-42 weeks gestation. Three of eight placentas after rhesus incompatibility had %H2O(T) above the mean +2SD of term placentas and five of 17 IUGR placentas were below the mean -2SD. The remaining placentas following maternal pre-eclampsia, hypertension, or diabetes had no apparent alteration in %H2O(T). A blind histological diagnosis of 'true' oedema was associated with both a significantly high %IW and %H2O(T). Perhaps this is due to alteration in placental cell volume regulation in certain situations. PMID- 8208671 TI - Syphilitic placentitis: an immunopathy. AB - The placentas of eight infants with congenital syphilis were examined by both immunohistochemical and immunofluorescent techniques. Significant IgM, C3 and rheumatoid factor reactivity were observed in all the syphilitic placentas. We postulate that their presence plays an important role in the evolution of the pathological changes. PMID- 8208672 TI - Oestrogen modulation with parturition in the human placenta. AB - An initial group of term (36-41 6/7 weeks), preterm (less than 36 weeks), and post-term (42 or more weeks) placentae were collected from women at delivery to determine the placental levels of important steroids and steroidogenic enzymes involved in the oestrogen synthesis pathway as a function of gestational age. A second group of placentae were obtained from women delivering at term before and after the onset of labour. Placentae were evaluated individually for cytosolic steroid hormone levels and microsomal steroidogenic enzyme activities. Oestradiol (E2), oestrone (E1), progesterone (P), and delta-4-androstenedione (A) were measured by radioimmunoassay in placental cytosols. Aromatase (AR), sulphatase (S), and 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta HSD) activities were assayed in placental microsomes. Cytosolic concentrations of E1, E2, P, and A did not differ with respect to gestational age. Correspondingly, the microsomal enzyme activities of 3 beta HSD, S, and AR did not vary as a function of gestational age. However, when patients at term who were in labour prior to delivery were compared to those who were not, the placental cytosolic level of E1 was found to be threefold higher in the non-labouring group (4572 versus 1427 pg/mg cytosolic protein, P < 0.025). Additionally, microsomal aromatase activity was also significantly higher in the non-labouring patients (46 versus 19 pM/min/mg protein, P < 0.025), while the E2 to P ratio in the labouring patients was twice that of the non-labouring group, a difference which was significant at the P < 0.025 level (Wilcoxon rank sum test). These data suggest that at term, prior to labour, the placental production of E1 by AR is high, and that AR activity and E1 levels fall significantly after the onset of labour. Also, the placental cytosolic concentration of the more active oestrogen, E2, demonstrates stable to rising levels with a significant increase in E2/P after the onset of labour. We theorize that in the term pregnancy prior to labour, E1 may represent a large but relatively inactive intracellular oestrogen pool which is maintained by high AR activity, and may function to protect the pregnant local uterine environment from the more oxytocic effects of E2. PMID- 8208673 TI - 15-Hydroxy-prostaglandin dehydrogenase activity in uterine tissues of late gestational and parturient cows. AB - 15-Hydroxy-prostaglandin dehydrogenase activity (PGDH) was measured in endometrium, allanto-chorion, allanto-amnion and the placenta from six cows during late gestation and six parturient cows during caesarean section. Under saturated substrate conditions PGDH activity was lower than 138 pmol g wet tissue 1 min-1 in all uterine tissues in both groups. Human placental reference samples showed a PGDH activity of 16,800 +/- 1200 pmol per g wet weight min-1 (n = 4). Under subsaturational conditions enzyme activity was demonstrated in endometrium and both fetal membranes. These results indicate that PGF2 alpha catabolism in bovine uterine tissue on day 262 and during parturition, contributes little to changing plasma PGFM concentrations. PMID- 8208674 TI - Laser scanning confocal examination and comparison of nidogen (entactin) with laminin in term human amniochorion. AB - Indirect immunofluorescence confocal microscopy was used to compare the distribution of nidogen (entactin) and laminin in term human amniochorion. Rabbit antiserum raised against recombinant mouse nidogen was immunoreactive with components of the amniotic epithelial basement membrane, chorion laeve basement membrane and maternally derived capillary basement membranes. Overall anti nidogen immunoreactivity co-distributes with laminin except in the extracellular matrix of the maternally derived decidua, the embryonically derived trophoblast and the apical surfaces of the amniotic epithelia. These differences lead us to suggest that nidogen and laminin may be independently expressed and are not always complexed together. Original observations include dramatic parallel nidogen rich striations in the decidual layer, the fact that the trophoblastic basement membrane appears to extend inwards forming a boundary layer to degenerate chorionic villi and the finding that the recently discovered collagen type IV rich microtrabeculae of the fibroblast layer also contain nidogen and laminin. PMID- 8208675 TI - [Iatrogenic demineralizing osteopathies]. AB - Long-term corticosteroid therapy is the most frequent and most severe cause of iatrogenic osteoporosis. Hypocalcaemia, subsequent to the induced negative calcium balance, may lead to secondary hyperparathyroidism. Corticosteroids also affect bone itself, probably by disrupting the production of growth factors. Bone resorption increases and bone formation decreases leading to a reduction in total bone mass. The relative immobilization resulting from the corticoid-induced myopathy or the underlying disease may accelerate the process. On the average, after one year of treatment, 5% of the bone mass is lost, and loss may reach as much as 10 to 30% at certain sites. Nearly 40% of all subjects on long-term corticosteroids suffer fractures. Other iatrogenic causes include anticonvulants which perturb phosphocalcium metabolism, 1-thyroxin which leads to bone loss when administered for hormone substitution, gonadotropin-releasing hormone antagonists which inhibit the hypophyseal-ovarian axis, tamoxifen (used in the treatment of breast cancer) which has an oestrogen-like effect, and other circumstances such as chemotherapy and long-term heparin. The gravity of iatrogenic osteroporosis thus requires preventive measures. Calcium and vitamin D supplements can compensate for impaired intestinal absorption of calcium but have no effect on bone density. One-alpha hydroxyl derivatives have been suggested but their effect remains controversial. Calcitriol can prevent bone loss in the lumbar vertebrae but hypercalcaemia occurs in one-fourth of the cases, limiting its use. Recent reports have shown that anti-oestroclastic agents may be useful. Nandrolone decaonate would have a favourable effect on bone loss but also causes virilization. In patent osteoporosis, fluorine can be combined with calcium resulting in increased lumbar bone density. Calcitonin and calcium can also be combined to induce a rise in bone density. The long-term effects of these treatments in terms of reduced fracture risk remain to be determined. A better understanding of the adverse effects of the different classes of corticosteroids is essential for optimal treatment. In cases requiring long-term therapy implicating the risk of iatrogenic osteoporosis, bone density quantitation can be a valuable means of evaluating bone loss, and of adapting preventive or corrective measures. PMID- 8208676 TI - [Ethical approach of clinical molecular genetics]. PMID- 8208677 TI - [Recombinant vaccine and extracting vaccine against hepatitis B in patients with kidney insufficiency: comparative immunogenicity]. AB - OBJECTIVES: Patients with chronic renal failure respond rather poorly to hepatitis B vaccines. A better response could be expected from recombinant vaccines including both the S and the pre-S2 antigens. We therefore prospectively compared the immunogenicity of plasma-derived Hevac B vaccine (H) with that of recombinant GenHevac B vaccine (G). METHODS: Vaccinations were performed in 120 non-dialyzed patients with chronic renal failure. The patients were randomly divided into two groups. Group G included 60 patients (24 males, mean age 58 +/- 16 years, mean creatinine clearance 25.3 +/- 12.6 ml/min) who were given the Hevac B vaccine at the dose of 5 micrograms. Group H included 60 patients (31 males, mean age 60 +/- 15 years, mean creatinine clearance 24.4 +/- 11.1 ml/min) who were given GenHevac B vaccine at the dose of 20 micrograms. All vaccinations were repeated at 0, 1, 2, 4 and 12 months. RESULTS: Following the fourth injection, seroconversion (anti-Hbs > or = 2 mlU/ml) was observed in 50/59 (85%) of the patients in group G versus 38/58 (67%) in group H (p < 0.02). Seroprotection (> or = 10 mlU/ml) was obtained in 42/59 (71%) vs 34/58 (59%), (NS) in the two groups respectively with a geometric mean titer of 112 versus 229 mlU/ml (NS) in responders. Following the booster injection at the 12th month, seroconversion was achieved in 48/51 (94%) vs 40/53 (76%) (p < 0.01) and seroprotection in 84% vs 70% (p = 0.053) respectively. The mean geometric titers were 879 and 1001 mlU/ml. CONCLUSIONS: Recombinant GenHevac B vaccine elicits seroconversion and seroprotection in a higher proportion of patients with chronic renal failure than the plasma-derived Hevac B vaccine, with comparably high antibody titers in responders. Therefore, GenHevac B vaccine should be recommended for vaccinating patients with chronic renal failure against hepatitis B. PMID- 8208678 TI - Time course analysis of the state of leukocyte adhesiveness/aggregation in patients with ischaemic heart disease. AB - OBJECTIVE: To determine the state of leukocyte adhesiveness/aggregation (LAA), in the peripheral blood of patients with ischaemic heart disease. METHODS: All the patients were examined during their hospitalization in the Chaim Sheba Medical Center Intensive Coronary Care Unit. The patients were divided into four diagnostic categories according to the clinical picture, electrocardiographic and echocardiographic findings, as well as enzyme levels. The white blood cell count (WBCC), the erythrocyte sedimentation (ESR) and the state of LAA were measured daily for a maximum of six days. RESULTS: The LAA in ten patients with acute anterolateral myocardial infarction, increased from 5 +/- 5% day one to 13 +/- 6% at day five; the respective values for ten patients with a diaphragmatic MI were 2 +/- 2% and 5 +/- 3% respectively. Normal LAA values were noted in ten patients with myocardial ischaemia, and no evidence for infarction, as well as in ten controls. The increases LAA correlated significantly with the erythrocyte sedimentation rate (r = 0.53, p < 0.0001), raising the possibility that fibrinogen is involved in induction and/or maintenance of an increased LAA. CONCLUSIONS: Our findings suggest that the state of LAA increases during the evolution of the infarction/inflammation process. Considering that sticky leukocytes may contribute to capillary flow retardation, the results of the present study would be relevant if optimal timing for anti-adhesive therapy is considered. PMID- 8208679 TI - [Discovery of an insulinoma during the first trimester of pregnancy]. AB - Insulinoma is a rare tumour reported in 10 cases during pregnancy. In most cases, hypoglycaemia occurred during the first trimester and no fetal malformations were noted. We report a new clinical case of insulinoma diagnosed at 6 weeks of amenorrhoea in a 25-year-old woman. Surgery performed at 17 weeks of amenorrhoea confirmed the presence of a 7 mm diameter endocrine tumour in the head of the pancreas and led to a cure. The pregnancy continued without complications, and at 35 weeks the patient gave birth to a 3.5 kg infant with no malformation. This case was investigated in terms of a possible physiopathological cause of insulinoma during pregnancy. There is good evidence that insulin secretion increases rapidly from the beginning of pregnancy because of beta-cell proliferation and enhanced beta-cell sensitivity to glucose stimulus as a result of hormonal changes, i.e., prolactin and/or placental lactogen secretion. Moreover, some studies have suggested that insulin sensitivity is enhanced during early pregnancy. Taken together, these phenomena may explain why insulinoma occurs early during pregnancy. Although repeated hypoglycaemia has caused teratogenic effects in animal models, no fetal malformation has been described in previous reports of insulinoma during pregnancy, whether cured or not. This is in agreement with prospective studies in insulin-treated pregnant diabetic women showing no correlation between hypoglycaemia and malformations. These results are encouraging with respect to such pregnancies which, however, require careful supervision. PMID- 8208680 TI - [Pelvic lymphoceles after kidney transplantation. Intraperitoneal marsupialization by celioscopy]. AB - OBJECTIVES: The appropriate treatment for symptomatic pelvic lymphoceles occurring after renal transplantation is still debated. External drainage exposes to risk of recurrence, infection or graft sclerosis and laparotomy has been required for intraperitoneal marsupialization in patients at risk. We report our experience with two cases treated by laparoscopic intraperitoneal marsupialization. PATIENTS: From November 1986 to September 1992, 170 renal transplantations were performed at our University Hospital. Lymphoceles developed in 12 cases and percutaneous puncture and irrigation was performed in all, successfully in 10. Relapse occurred in 2 patients--one 50-year-old woman with chronic glomerulonephritis and one 41-year-old man on peritoneal dialysis for polycystic renal disease--recipients of cadaver kidneys. SURGICAL TECHNIQUE: The laparoscopy was conducted under general anaesthesia. Four trocars were inserted, a 10 mm via the umbilicus for the optical system and three 5 mm trocars via the right and left flank and the left iliac fossa. A long puncture needle was used to drain the lymphocele and a localized collection and a large peritoneal window was created. The abdominal cavity was abundantly washed before withdrawing. RESULTS: Operation time was 35 minutes and conversion to laparotomy was not required. The only complication was a haematoma at one insertion site. Patients were discharged on day 2 and on day 1 with an unchanged immunosuppressor regimen. At 10 months follow-up, the patients were symptom-free and echography was normal. CONCLUSIONS: Surgical treatment of lymphoceles can be successfully performed by laparoscopy. The choice between conservative treatment and laparoscopic surgery remains to be determined. PMID- 8208681 TI - [Oncogenes and anti-oncogenes in lung cancer]. AB - In all normal cells, two type of genes, oncogenes and anti-oncogenes, are expressed and control cell proliferation and differentiation. Cell growth is stimulated by oncogenes and inhibited by anti-oncogenes. Cancerization involves loss of control due to defective gene expression either by overexpression of a normal protein (loss of quantitative control) or expression of an abnormal protein (loss of qualitative control). Several oncogenes have been identified. They include three oncogenes, c-myc, N-myc and L-myc, known to be overexpressed in small-cell carcinomas of the lung. Point mutations of the oncogene K-ras is found in 15 to 30% of adenoma carcinomas, especially in smokers. Loss of anti oncogene function has also been described in processes leading to lung cancer. Chromosome abnormalities, for example the 3p14-23 deletion described in 1982, are found in 100% of small-cell carcinomas and in 50% of non-small-cell carcinomas. This deletion is never found in normal tissue. The gene involved has not yet been cloned. Other mutations or deletions include the RB gene, necessary for neuroendocrine differentiation, and the p53 gene which has undergone mutation in 50% of the non-small-cell carcinomas and 70% of the small-cell carcinomas. These acquired mutations are strongly associated with tobacco smoking. Oncogenes and anti-oncogenes play an important role in the complex step-wise process leading to cancerization. As tumour characterization becomes more precise and precancerous states better controlled, future treatments may relief on inhibiting tumoural growth by using drugs which would substitute for the lost effect of anti oncogenes or inhibit activation of an oncogene. But at the present time, it is still difficult to define criteria predicting high risk of postoperative relapse or resistance and further studies investigating the correlation between genetic abnormalities and clinical staging and survival curves are required. PMID- 8208682 TI - [Abscess in the omentum following loss of biliary calculi in the peritoneal cavity]. PMID- 8208683 TI - [Treatment of asthma: estimation of the cost of adverse effects associated with ketotifen]. PMID- 8208684 TI - [Acute pericarditis during acute diabetic metabolic decompensations]. PMID- 8208685 TI - [Vitamin D during fasting]. PMID- 8208687 TI - [Thyroid metastasis]. PMID- 8208686 TI - [Diabetic nephropathy: screening by testing for micro-albuminuria with reagent strips (Micral-Test)]. PMID- 8208688 TI - Colonoscopy in the elderly. PMID- 8208689 TI - [Value of magnetic resonance imaging in myeloma]. AB - Magnetic resonance imagery (MRI) of the spinal cord has become a standard method and its diagnostic and prognostic power in multiple myeloma has been widely demonstrated. Before treatment, MRI reveals two basic types of abnormalities yielding focal and diffuse signals. Focal lesions are seen as localized hyposignals on spin echo T1 sequences (SET1) and are enhanced by injection of gadolinium and changed to hypersignals in T2 weighted sequences. These images identify nodular tumoural masses. Diffuse lesions are seen most often as homogeneous SET1 images with an intensity similar to the vertebral body. This type of image is not specific of tumoural infiltration and can be benign in nature. The second type of diffuse signal is often called a "salt and pepper" image due to the juxtaposition of multiple hyposignals (suspected tumoural tissue) and hypersignals (fat tissue). We have observed this type of image in 27% of our series of multiple myelomas. The capacity of MRI to detect myelomas located in bone tissue is much greater than conventional radiography of the spine and is particularly sensitive to expansive tumoural lesions threatening the cord. MRI should always be performed as part of the initial work-up even in the absence of clinical signs. There is a good correlation between MRI of focal tumours and the biological response to treatment, although other biological markers may be more precise and easier to obtain. MRI can also be used to differentiate between benign monoclonal gammapathy and multiple myeloma, particularly in cases where there is a disagreement between the clinical and laboratory data. We have also studied MRI in solitary plasmacytomas of the spine. PMID- 8208690 TI - [Ethical and psychologic problems in pregnancies after donation of ovocytes]. PMID- 8208691 TI - [Hypothalamic-pituitary-adrenal function in primary hypothyroidism]. AB - OBJECTIVES: Hypothyroidism is known to lead to a certain degree of functional insufficiency of the adrenal gland by affecting both the hypophyseal axis and peripheral metabolism of cortisol. This study was conducted to evaluate hypothalamic, pituitary, and adrenal function in a homogeneous group of patients with long-standing major hypothyroidism. METHODS: Forty-five patients (32 females, 13 males; mean age 42.9 +/- 9.6 years; range 20-59) with major primary hypothyroidism known to be long-standing (> 1 year in 1 and for an undetermined duration of several years in all the others) were included. Twenty-nine age matched subjects served as controls. Insulin-induced hypoglycaemia and oral metyrapone tests were performed before and after treatment had induced euthyroidism. Plasma ACTH and cortisol were measured every 20 min for 2 hours during the hypoglycaemia test and ACTH before and after the last dose of metyrapone. Plasma cortisol levels were determined before and 30 min after injection of tetracosactide. RESULTS: Baseline ACTH and cortisol were not different in patients and controls and were unchanged by treatment. ACTH and cortisol response to hypoglycaemia were weaker in patients with ongoing hypothyroidism (p < 0.05 vs controls) and improved significantly (p < 0.05 vs baseline) after treatment. Adreno-cortical response to exogenous ACTH stimulation was weaker in patients with hypothyroidism (p < 0.05 vs controls) and returned to normal after treatment. CONCLUSIONS: Modifications of the hypothalamic-pituitary adrenal system resulting from hypothyroidism were minimal and evidenced only by dynamic exploration. Levels returned to normal after adequate treatment and the deficit restricted to the hypothalamus and pituitary might also involve the adrenal gland. PMID- 8208692 TI - [Endocarditis caused by Cardiobacterium hominis]. AB - The incidence of endocarditis due to Cardiobacterium hominis is probably underestimated because clinical presentations vary greatly and culture of this Gram negative germ is difficult. A 48-year-old man with a past history of post streptococcic aortic regurgitation was hospitalized twice within 1 week for fever (38 degrees C) and junctional tachycardia which responded to amiodarone. Subsequently, infero-apical necrosis was documented. Based on the result of the laboratory tests, coronary embolism was suspected although 12 blood cultures were negative. The patient recovered well with a standard antibiotic treatment. Fifteen days later, the blood cultures revealed Cardiobacterium hominis. Antibiotic therapy was adapted and aortic valve replacement was programmed. Two months later the patient died from uncontrollable left heart failure. A 63-year old man who had had mitral valve replacement 10 years earlier for Streptococcus mitis endocarditis was hospitalized for fever (38 degrees C) and a painful left calf. Phlebocavography eliminated deep vein thrombosis and a complete cardiac work-up was inconclusive. Endocarditis was suspected although blood cultures were negative. The patient was given oral penicillin and discharged after one week. Three months later, the patient was again febrile (38 degrees C) and suffered a cerebral vascular event. Fourteen days after blood sampling, cultures revealed Cardiobacterium hominis. The patient's haemodynamic status worsened and valve replacement with atrioplasty was performed. Outcome after 4 years follow-up has been favourable. Endocarditis due to Cardiobacterium hominis, a saprophitic germ of the upper airway and the female genital tract, has been reported in 64 cases in the literature. The clinical picture is often limited to fever and a heart murmur and laboratory tests show an accelerated erythrocyte sedimentation rate and hyperleukocytosis. Inflammatory type anaemia is often found due to the latency of the endocarditis. Complications are frequent and can be fatal due to massive pulmonary emboli, cerebral vascular events or irreversible heart failure. C. hominis is sensitive to amoxycillin and netilmicin. Surgical treatment of the valvulopathy is indicated. PMID- 8208693 TI - [Nocardia farcinica infection. Cutaneous form in an immunodepressed patient]. AB - Nocardiosis is a rare localized or systemic infection caused by bacteria of the Actinomycetaceae family. Nocardia farcinica, recently identified as a distinct species from Nocardia asteroides, characteristically causes severe systemic infections and is particularly resistant to antibiotics. We report a case of nocardiosis observed in a patient receiving general corticosteroid therapy for bullous pemphigoid and who developed a sub-cutaneous abscess of the breast. N. farcinica was identified on puncture specimens and found to be resistant to beta lactams, aminosides, cyclines, chloramphenicol, fosfomycin and pefloxacin. No dissemination beyond the skin was observed. The abscess was drained and cleaned surgically and cicatrization was uneventful. Six weeks later the patient was again hospitalized for an inflammatory abscess of the left buttocks which was drained surgically. N. farcinica was again identified and a complete work-up eliminated dissemination. Cotrimoxazole was given as a long-term therapy (480 mg trimethoprim, 2.4g sulfamethoxazole) for 6 months and was well tolerated. No recurrence was observed. PMID- 8208694 TI - [Microsporidioses]. AB - Microsporidia are worldwide ubiquitous intracellular protozoan parasites infecting most major groups of the animal kingdom. In humans, microsporidiosis has recently emerged as a significant cause of morbidity in immunocompromised patients, and particularly in patients with acquired immunodeficiency syndrome (AIDS). Parasites of the genus Encephalitozoon cause keratoconjunctivitis and disseminated infections. In 15 to 30% of patients with advanced stage AIDS, Enterocytozoon bieneusi is the causative agent of major chronic diarrhoea. Clinical manifestations include numerous (2 to 8) and abundant, irregular liquid or semi-liquid stools without evidence of intestinal haemorrhage. Impaired absorption is aggravated by food intake causing the patients to restrain from eating and subsequent weight loss is progressive and irreversible. The diarrhoea becomes permanent and leads to dehydration ad malnutrition. Spontaneous remissions have been observed but are always of short duration. Microsporidiosis has also been found in ocular localizations in patients with AIDS; these keratopathies may be due to Encephalitozoon cuniculi, the only known species in mammals but E. hellem, a morphologically identical but antigenically different species has been identified. Other visceral localizations have been observed. Diagnosis of microsporidiosis relies on the demonstration of spores and/or intracellular parasites in stools, urine or tissue biopsies. The responsible agent can generally be identified by light microscopy, but differentiation between species still requires electron microscopy. New light and fluorescent microscopic techniques have been proposed for easier recognition of spores in various pathological samples. Immunodiagnostic techniques are limited due to the lack of correlation between antibodies detection and clinical manifestations. Although the parasite can be identified and although its cycle has been carefully studied, no prophylactic action can be taken because the mode of transmission remains largely unknown. Many treatment protocols have been tried but none have been found to be effective. Very little pharmacological data has been accumulated. Microsporidiosis is, and will remain, a major opportunistic infectious disease causing uncontrollable debilitating malnutrition in AIDS patients unless an effective treatment can be found, a major challenge for medical science. PMID- 8208695 TI - Interventional cardiology: state of the art. AB - Since the advent of percutaneous transluminal coronary angioplasty (PCTA) in 1977, a new breed of cardiologists was born "Interventional Cardiologists". To date, a wide range of new interventions have been developed including percutaneous closure of atrial septal defects and balloon dilatation of the pulmonary valve and mitral valvuloplasty among others. In 1994, the final position of interventional cardiology is not fully defined but indicates what can be expected in the near future. Conventional coronary angioplasty presently accounts for over 90% of all coronary interventions and is likely to remain the cornerstone of coronary interventions. New techniques include stents which have been shown to be effective in acute and threatening occlusions as part of the armamentarium against restenosis. The Rotablator is a technique which uses an olive-shaped high-speed burr coated with diamond chips used for debulking lesions though to represent a high risk/low success rate for balloon angioplasty. Directional coronary atherectomy, transluminal extraction catheters, and Rotacs (a low-speed rotator) have also been developed. Laser angioplasty, which initially created great enthusiasm, probably will be of limited use. Mitral balloon valvuloplasty has emerged as the most common balloon valvuloplasty performed world-wide. It can be performed with or without fluoroscopy, particularly useful in pregnant women. Balloon valvuloplasty is also the treatment of choice in cases of pulmonary stenosis and balloon dilatation of the aortic valve, initially developed for children is now indicated in adults with the exception of elderly patients with calcified valves for whom valve replacement is indicated. Other interventions currently performed include balloon angioplasty for aortic coarctation following surgical repair and transcatheter closure of shunts. Patent ductus arteriosus, atrial septal defect and ventricular septal defect are choice indications. Certain congenital heart diseases including the creation of atrial septal defects in neonates whose survival depends on such a shunt and the treatment of pulmonary branch stenosis, venous obstructions, discrete subaortic stenoses and dilatation of the infundibular stenosis. Coil embolization of arteriovenous fistulae has also been developed. Finally, ablative techniques of invasive electrophysiology have further widened the indications of interventional techniques in cardiology which will continue to develop as an important pole of research and clinical applications in the future. PMID- 8208696 TI - [An original cause of elevation of serum CA 125]. PMID- 8208697 TI - [Bronchogenic cyst, an unexpected cause of an adrenal incidentaloma]. PMID- 8208698 TI - [Nocardia asteroides meningitis without brain abscess in an non-immunodepressed adult]. PMID- 8208700 TI - [Paralysis of the dorsal nerve of the scapula: an unusual cause of scapular displacement]. PMID- 8208699 TI - [Tertiary hyperparathyroidism revealing celiac disease in adults]. PMID- 8208701 TI - [Scintigraphy using amyloid P component labelled with iodine 123: a new method of evaluation of amyloidosis]. PMID- 8208702 TI - [Assessment of the deepness of coma in children. Evolution of clinical thoughts]. AB - Clinical assessment is an essential fundamental element in the evaluation of comatose states, particularly in children. Paediatricians quickly recognized that the early Glasgow Coma Scale, used for over 20 years in adults, is inadapted for children because it lacks brain stem criteria, involves interpretation of motor response (particularly difficult in infants) and uses verbal response which is of little value before language acquisition. The first attempt at standardized coma assessment in children was the Paediatric Coma Scale, developed in Australia in 1982. This scale improved on the Glasgow scale, removing the motor retraction response, modifying the verbal response scale (normal, words, sounds, crying, or none) and quantifying the best possible score as a function of age. In 1983 a fundamental modification was proposed in the Jacob scale. Besides removing the motor retraction response, this scale replaced the verbal scale with one based on ocular behaviour, thus evaluating consciousness of presence or stimulation. The vestibular response and pupil reactions were also included to assess brain stem activity. In 1987, we introduced the Bicetre scale which uses ocular behaviour instead of verbal response and separates ocular diameter as a specific criteria. Assessment of four reflexes (mimic, photomotor, cornea and cough) provides precise information on the activities of the different levels of the brain stem. Several comparative studies have been conducted to determine the positive predictive value and interpersonal variability of these scales. In a prospective multicentric study of 277 comatose children aged 6 months to 15 years, we found that the Bicetre scale had a positive predictive value of 94% for good outcome at 24 hours and that interpersonal disagreement occurred in only 10.1% of 65 cases studied (compared with 13.5% for the Glasgow scale which was studied simultaneously). Paediatricians now have reliable clinical scales for assessing the conscious level in children. PMID- 8208703 TI - [Hydatid cysts of the liver. Therapeutic and prognostic classification. 378 cases]. AB - OBJECTIVES: We retrospectively examined our clinical data on hydatic cysts of the liver collected over the last 10 years in order to determine a classification which could be used to guide future therapeutic decisions. METHODS: From 1982 to 1992, hydatic cysts of the liver were surgically removed in 378 patients (mean age 38 +/- 12 years). Echography had been performed in all patients. Other preoperative investigations included computerized tomodensitometry (n = 57) and arteriography of the caeliomesenteric arteries (n = 12). Histological examination of surgical specimens included research for parasite inclusions within the pericyst and the hepatic parenchyma. RESULTS: Single cysts were found in 65.7% of the cases, double cysts in 20% and multiple cysts in 12.5%. Histology revealed parasites in the pericyst in 129 cases (34%) and a fistula from the cyst to the bile duct was observed in 47 cases (12.5%). A classification was obtained based on 5 criteria: localization and number of cysts, cyst content, morphology of the pericyst and biliary-cyst fistula. CONCLUSION: The excellent correlation between this classification and prognosis provides a valuable tool for the management of hepatic hydatic cysts. PMID- 8208705 TI - [Primary adrenal lymphoma. Report of a case]. AB - The adrenal gland is affected in about 25% of patients with diffuse lymphoma. Conversely, primary lymphoma is a rare cause of non-secreting adrenal tumour. We observed a recent case with exclusive right adrenal localization. An 84-year-old woman was hospitalized for asthenia, anorexia and a 3-kg weight loss. The past history included coronary heart disease. Physical examination was normal and the hemogram revealed pancytopenia. No lymphomatous infiltration was seen on the myelogram or the bone marrow biopsy. Echography of the abdomen showed a well limited 10 cm mass above the right adrenal gland, distinct from the liver; the left gland had a normal aspect. Hormone assays were within normal limits. The right adrenal gland was removed surgically and histology revealed diffuse proliferation of medium to large sized lymphoid cells invading the entire gland. Immunohistochemistry suggested lymphoid B origin. No curative treatment was begun, but 2 months after surgery local invasion required polychemotherapy. The patient died of septic shock 5 days later. Serum cortisol measured during the septic shock eliminated adrenal gland failure. Malignant primitive non-Hodgkinien lymphomas are extremely rare and usually discovered incidentally. The tumour is always large and sometimes accompanied by adrenal insufficiency when the lesion is bilateral. In spite of suggestive imagery the diagnosis is based on the pathology examination. The lesion is usually a high-grade malignant phenotype B lymphoma. Treatment relies on chemotherapy but is disappointing. PMID- 8208704 TI - Anaerobic threshold in patients with chronic cardiac failure due to ischaemic heart disease. AB - OBJECTIVES: Anaerobic threshold was measured to examine its relationship with venous lactate levels and the reproducibility of gas exchange methods. METHODS: Twenty patients with chronic cardiac failure due to ischaemic heart disease underwent two successive treadmill tests with measurements of respiratory gas exchange. RESULTS: An anaerobic threshold was demonstrated in 78 p. 100 of tests, by plotting either VE/VO2 or VCO2/VO2, and reproducibility between the two tests was satisfactory. Peripheral venous lactate levels did not increase from rest to the end of the exercise stage prior to the anaerobic threshold, but did increase significantly thereafter. Where an anaerobic threshold could be demonstrated, it was reproducible and correlated strongly with peak achieved VO2. CONCLUSION: However, as measurement of anaerobic threshold requires exercise to 90 p. 100 maximum VO2, it may be preferable to continue until limiting symptoms, and use peak achieved VO2 as the end point. Anaerobic threshold is a reproducible measure of anaerobic exercise capacity. PMID- 8208706 TI - [Huntington disease. Current state of research]. AB - Huntington's disease is a hereditary disease with autosomal dominant transmission which generally occurs in adults. The gene was discovered in 1983 and the genetic abnormality in March 1993. The most commonly recognized clinical manifestation is choreiform movements although other signs often appear more invalidating to family and friends. Cognitive decline, modifications in behaviour, and sometimes psychiatric disturbances are perceived as the major handicap in everyday life. In this review, emphasis has been placed on late onset forms of the disease. Recent research has focused on morphologic and functional imagery, the neuropathologic stages of selective neurone loss beginning in the striatum, and the role of excitotoxic amino-acids. Certain ethical considerations must be addressed when determining prognosis. Predictive tests and follow-up must be prepared and conducted scrupulously and proposed to voluntary, informed, major subjects at risk. Tests should be performed by a qualified laboratory working on anonymous samples, independent of the clinical team, and should be given to the subject orally by a genetic counsellor. A prenatal test may be requested by parents at risk. The question of treatment, which to date can only offer symptomatic relief, should be re-addressed in light of the recent discovery of the mutation published in March 1993. PMID- 8208707 TI - [Angioscan with three dimensional reconstruction: value for the diagnosis of stenoses of the renal artery]. PMID- 8208708 TI - [Basedow ophthalmopathy: treatment with intravenous immunoglobulins. 2 cases]. PMID- 8208709 TI - [Cacosmia during treatment with zidovudine]. PMID- 8208710 TI - [Proteus mirabilis osteomyelitis in an adult with homozygous sickle cell anemia]. PMID- 8208711 TI - [Spider bites in south Corsica]. PMID- 8208712 TI - [Non toxic Corynebacterium diphtheriae endocarditis. A case]. PMID- 8208713 TI - [Severe early pulmonary embolism after blockage of the vena cava]. PMID- 8208714 TI - [Asymptomatic myxoma of the right atrium. Value of nuclear magnetic resonance]. PMID- 8208715 TI - [Myocardial infarction after attempt of autolysis with insulin]. PMID- 8208716 TI - [PRIMARY infection caused by Parvovirus B19 revealed by isolated febrile lumbalgia]. PMID- 8208717 TI - [Idiopathic T+CD4 lymphocytopenia: an asymptomatic form followed-up for two years]. PMID- 8208718 TI - [Myoclonia in patients treated with tricyclic antidepressive agents. Prospective evaluation]. PMID- 8208720 TI - [Diabetic arteritis: therapeutic implications based on the profile of the lesion]. PMID- 8208719 TI - [Adenocarcinoma of the ethmoid bone in patients with no occupational exposure to wood]. PMID- 8208721 TI - [Thrombocytopenia during malaria. Study of 242 cases]. PMID- 8208722 TI - [Two ischemic cerebral accidents in treated Horton disease: caused by adrenal cortex hormone therapy?]. PMID- 8208723 TI - Correlated mutations and residue contacts in proteins. AB - The maintenance of protein function and structure constrains the evolution of amino acid sequences. This fact can be exploited to interpret correlated mutations observed in a sequence family as an indication of probable physical contact in three dimensions. Here we present a simple and general method to analyze correlations in mutational behavior between different positions in a multiple sequence alignment. We then use these correlations to predict contact maps for each of 11 protein families and compare the result with the contacts determined by crystallography. For the most strongly correlated residue pairs predicted to be in contact, the prediction accuracy ranges from 37 to 68% and the improvement ratio relative to a random prediction from 1.4 to 5.1. Predicted contact maps can be used as input for the calculation of protein tertiary structure, either from sequence information alone or in combination with experimental information. PMID- 8208724 TI - Investigation of the functional interplay between the primary site and the subsite of RNase T1: kinetic analysis of single and multiple mutants for modified substrates. AB - We report on the functional cooperativity of the primary site and the subsite of ribonuclease T1 (RNase T1; EC 3.1.27.3). The kinetic properties of the single Tyr 38-Phe and Asn-98-Ala mutants have been compared with those of the corresponding double mutant. The Tyr-38-Phe mutation has been used to probe enzyme-substrate interactions at the primary site; the Asn-98-Ala mutation monitors subsite interactions. In addition to the dinucleoside phosphate substrate GpC, we measured the kinetics for GpMe, a synthetic substrate in which the leaving nucleoside cytosine has been replaced by methanol. All data were combined in a triple mutant box to analyze the interplay between Tyr-38, Asn-98, and the leaving group. The free energy barriers to kcat, introduced by the single Tyr-38 Phe and Asn-98-Ala mutations are not additive in the corresponding double mutant. The energetic coupling between both mutations is independent of the binding of the leaving cytosine at the subsite. We conclude that the coupling of the Tyr-38 Phe and Asn-98-Ala mutations arises through distortion or reorientation of the 3' guanylic acid moiety bound at the primary site. The experimental data indicate that the enzyme-substrate interactions beyond the scissile phosphodiester bond contribute to catalysis through the formation of new or improved contacts in going from ground state to transition state, which are functionally independent of primary site interactions. PMID- 8208725 TI - Analysis of C alpha geometry in protein structures. AB - The polypeptide of a protein molecule can be considered as a chain of C alpha atoms linked by pseudobonds between the C alpha atoms of successive amino acid residues. This paper presents an analysis of the angle and dihedral angles made by these pseudobonds in protein structures determined at high resolution by X-ray crystallography. This analysis reveals a strong correlation between C alpha geometry and the protein fold. The regular features of protein secondary structure such as alpha-helix and beta-sheet are very clearly defined. In addition, it is possible to identify with some confidence the discrete populations of particular conformations of beta-turn. Comparison with the traditional Ramachandran type of plot demonstrates that an analysis of protein structure on the basis of C alpha geometry provides a richer description of protein conformation. In addition, the characteristics of this geometry could be a useful guide in model building of protein structure. PMID- 8208726 TI - Monte Carlo simulations of protein folding. I. Lattice model and interaction scheme. AB - A new hierarchical method for the simulation of the protein folding process and the de novo prediction of protein three-dimensional structure is proposed. The reduced representation of the protein alpha-carbon backbone employs lattice discretizations of increasing geometrical resolution and a single ball representation of side chain rotamers. In particular, coarser and finer lattice backbone descriptions are used. The coarser (finer) lattice represents C alpha traces of native proteins with an accuracy of 1.0 (0.7) A rms. Folding is simulated by means of very fast Monte Carlo lattice dynamics. The potential of mean force, predominantly of statistical origin, contains several novel terms that facilitate the cooperative assembly of secondary structure elements and the cooperative packing of the side chains. Particular contributions to the interaction scheme are discussed in detail. In the accompanying paper (Kolinski, A., Skolnick, J. Monte Carlo simulation of protein folding. II. Application to protein A, ROP, and crambin. Proteins 18:353-366, 1994), the method is applied to three small globular proteins. PMID- 8208727 TI - Monte Carlo simulations of protein folding. II. Application to protein A, ROP, and crambin. AB - The hierarchy of lattice Monte Carlo models described in the accompanying paper (Kolinski, A., Skolnick, J. Monte Carlo simulations of protein folding. I. Lattice model and interaction scheme. Proteins 18:338-352, 1994) is applied to the simulation of protein folding and the prediction of 3-dimensional structure. Using sequence information alone, three proteins have been successfully folded: the B domain of staphylococcal protein A, a 120 residue, monomeric version of ROP dimer, and crambin. Starting from a random expanded conformation, the model proteins fold along relatively well-defined folding pathways. These involve a collection of early intermediates, which are followed by the final (and rate determining) transition from compact intermediates closely resembling the molten globule state to the native-like state. The predicted structures are rather unique, with native-like packing of the side chains. The accuracy of the predicted native conformations is better than those obtained in previous folding simulations. The best (but by no means atypical) folds of protein A have a coordinate rms of 2.25 A from the native C alpha trace, and the best coordinate rms from crambin is 3.18 A. For ROP monomer, the lowest coordinate rms from equivalent C alpha s of ROP dimer is 3.65 A. Thus, for two simple helical proteins and a small alpha/beta protein, the ability to predict protein structure from sequence has been demonstrated. PMID- 8208728 TI - Structural basis for type I and type II deficiencies of antithrombotic plasma protein C: patterns revealed by three-dimensional molecular modelling of mutations of the protease domain. AB - Familial deficiency of protein C is associated with inherited thrombophilia. To explore how specific missense mutations might cause observed clinical phenotypes, know protein C missense mutations were mapped onto three-dimensional homology models of the protein C protease domain, and the implications for domain folding and structure were evaluated. Most Type I missense mutations either replaced internal hydrophobic residues (I201T, L223F, A259V, A267T, A346T, A346V, G376D) or nearby interacting residues (I403M, T298M, Q184H), thus disrupting the packing of internal hydrophobic side chains, or changed hydrophilic residues, thus disrupting ion pairs (N256D, R178W). Mutations (P168L, R169W) at the activation site destabilized the region containing the activation peptide structure. Most Type II mutations involved solvent-exposed residues and were clustered either in a positively charged region (R147W, R157Q, R229Q, R352W) or were located in or near the active site region (S252N, D359N, G381S, G391S, H211Q). The cluster of arginines 147, 157, 229, and 352 may identify a functionally important exosite. Identification of the spatial relationships of natural mutations in the protein C model is helpful for understanding manifestations of protein C deficiency and for identification of novel, functionally important molecular features and exosites. PMID- 8208729 TI - Ion pair formation involving methylated lysine side chains: a theoretical study. AB - Lysine residues with one, two, or three methyl groups substituted on the epsilon nitrogen atom are found in many proteins. To evaluate the effect of the posttranslational methylation on ion-pair formation we have performed semiempirical and ab initio molecular orbital calculations, using the AM1 method and the 6-31G* basis set, respectively. Combinations of various methylated forms of methylamine and ethylamine with formate, acetate, and dimethyl phosphate were studied as model compounds. This approach allowed us to obtain information relevant to the interaction of the modified Lys residues with carboxylate groups of proteins, and the backbone of nucleic acids. We have found that the interaction energy decreases with an increasing number of methyl groups. Inclusion of a solvent reaction field in the semiempirical calculations gave reasonable values for the interaction energy in aqueous solution, when formate and acetate were the counterions. These studies suggest that, in addition to other factors, a weakening of ionic interactions contributes to the various physiological effects of lysine methylation. PMID- 8208730 TI - Lobster enolase crystallized by serendipity. AB - An unknown protein crystallized from a lobster muscle preparation in which arginine kinase was the majority component. It was identified as enolase by peptide sequencing and activity testing, and a SIRAS electron density map showed its three-dimensional structure to be very similar to that of yeast enolase. PMID- 8208731 TI - Preliminary X-ray analysis of Escherichia coli GMP synthetase: determination of anomalous scattering factors for a cysteinyl mercury derivative. AB - We have initiated a project to determine the three-dimensional structure of GMP synthetase (GMPS) from Escherichia coli. GMPS catalyzes the conversion of XMP to GMP in the final step of de novo guanine nucleotide biosynthesis, and is a member of the glutamine amidotransferase family: a group of enzymes responsible for the assimilation of nitrogen into compounds such as amino acids, purine and pyrimidine bases, amino sugars, and antibiotics. The E. coli guaA gene encoding GMPS was cloned into a tac expression vector, overexpressed, and its gene product purified. Conditions for the growth of protein crystals were developed using recombinant GMPS in the presence of MgCl2, ATP, and XMP. The crystals are monoclinic, space group P2(1), with cell parameters of a = 156.0 A, b = 102.0 A, c = 78.8 A, beta = 96.7 degrees. Diffraction data to 2.8 A spacings were collected on a Xuong-Hamlin area detector with an overall Rsym of 5.2%. Both the volume of the unit cell and the peaks in the self-rotation function are consistent with one GMPS tetramer of D2 symmetry in the crystallographic asymmetric unit. Previously, GMPS has been observed only as a dimer in solution. GMPS was covalently modified with p-chloromercuribenzylsulfonic acid (PCMBS), and its X-ray fluorescence spectrum was measured through the LIII absorption edge of mercury. Anomalous scattering factors for cysteinyl mercury were derived from this spectrum, and the feasibility of structure determination by multi-wavelength anomalous diffraction was evaluated. The optimal MAD dispersive signal is 4.5% of magnitude of F, and the optimal MAD Bijvoet signal is 7.5% of magnitude of F at a concentration of approximately 1 mercury per 10-kDa protein. The anomalous scattering factors tabulated here should be transferable to cysteinyl mercury in other proteins. PMID- 8208732 TI - The physiology and biochemistry of skeletal muscle atrophy as a function of age. AB - The skeletal muscles are an important entity in the proper function of aging animals and humans. Studies have shown that until humans are 60-70 years old, age related changes in muscle function and structure are relatively small, while after 70 years, these alterations are accelerated considerably. Factors responsible for the "aging" of skeletal muscles are complex and include intrinsic biochemical changes in muscle metabolism, changes in the distribution and size of muscle fibers, and a general loss of muscle mass. In addition, other factors like the control of muscle contraction by the motor neural system and the influence of external conditions such as exercise, immobility, nutrition and others may also contribute to the age-related decrease in muscle functions. Studies have shown that with age there is some loss of peripheral motor neurons, reduction in the number of motor units, alterations in the neuromuscular junctions, and selective denervation of Type II muscle fibers. These findings led to the concept of denervation atrophy of skeletal muscles as one of the major mechanisms for muscle degeneration in old age. However, it should be emphasized that the extent of age related changes varies from muscle to muscle, and some do not seem to be affected by age. For example, it has been shown recently, in animal studies, that weight bearing muscles are much more susceptible to senescent processes than non-weight bearing muscles. More work is needed to clarify the contributions of the various factors, especially the role of muscle training in alleviating the symptoms of age-related muscle atrophy. PMID- 8208733 TI - Enterokinase. AB - Enterokinase is a glycoprotein and is now designated enteropeptidase (E.C.3.4.4.8.). It is present in the duodenal and jejunal mucosa. Pancreatic proteolytic enzymes are secreted as proenzymes. Enterokinase converts trypsinogen to trypsin in the duodenal lumen. Duodenopancreatic reflux of duodenal enterokinase may be important in the pathogenesis of experimental and clinical acute pancreatitis. Congenital enterokinase deficiency is a distinct clinical entity characterized by diarrhea, failure to thrive, hypoproteinemia, and edema. Acquired enterokinase deficiency may occur in some diffuse small bowel diseases. Steatorrhea of celiac spruce may be due partly to the fact that deficiency of secretin and cholecystokinin may interfere with the action of enterokinase. The interrelationship between secretin, cholecystokinin, enterokinase, and bile salts is not completely understood. PMID- 8208734 TI - The influence of 25-hydroxycholesterol on phosphatidylinositol content in cultured smooth muscle cells. AB - The effect of 25-hydroxycholesterol on phosphatidylinositol content was studied in subconfluent human arterial smooth muscle cells exposed to myo-[2-3H]inositol for 90 min and then to 25-hydroxycholesterol at different concentrations or for different incubating periods. Ethanol at a concentration of 0.05% in culture medium was used as control. The results demonstrate that an increased incubation time or an increase in the concentration of 25-hydroxycholesterol produced an increase in phosphatidylinositol and its degraded products. The ratio of precursor to product at each stage of phosphatidylinositol turnover in 25 hydroxycholesterol-treated cells, however, was not different from that in control cells. The data indicate that the presence of 25-hydroxycholesterol in the media induced general activation of phosphatidylinositol synthesis and turnover. PMID- 8208735 TI - The results of exposure to immobilization, hemorrhagic shock, and cardiac hypertrophy on beta-endorphin in rat cardiac tissue. AB - In the present study, beta-endorphin (BE), beta-lipotropin (B-LPH) and the ratio of beta-endorphin to beta-lipotropin (BE:B-LPH) were determined in rat cardiac tissue in response to physical stress induced by immobilization and cardiovascular stress resulting from hemorrhagic shock and pressure overload induced cardiac hypertrophy. As compared with controls, BE was increased and B LPH was decreased in cardiac tissue from animals subjected to immobilization, and there was also a significant rise in the ratio of BE:B-LPH. Cardiac BE remained unchanged following hemorrhage, while B-LPH was diminished, resulting in an increase in the ratio of BE:B-LPH. Similarly, the concentration of BE was unchanged, the concentration of B-LPH was significantly diminished and the ratio of BE:B-LPH was significantly increased in hypertrophied hearts. Thus, immobilization-induced stress, hemorrhagic shock, and cardiac hypertrophy all increased the ratio of BE:B-LPH in the heart. However, it appears that immobilization stress induces an increase in cardiac BE, whereas cardiovascular stress results in a preservation of BE in the heart and a reduction in cardiac B LPH. The data suggests that physical stress (induced by immobilization) and cardiovascular stress (i.e., hemorrhage, hypertrophy) have differential effects on the synthesis of BE and the post-translational processing of proopiomelanocortin in the heart. Furthermore, the alterations in cardiac tissue BE and possibly B-LPH may play a role in the response of the heart to physical and cardiovascular stress. PMID- 8208736 TI - Lipoprotein alterations in the spontaneously hypertensive rat fed diets deficient in selenium and vitamin E. AB - Both vitamin E and selenium (Se) are antioxidant nutrients that play important roles in preventing in vivo lipid peroxidation. In this investigation, Se and vitamin E were found to influence lipoprotein levels in the spontaneously hypertensive rat (SHR). Four-week-old inbred SHRs were fed a basal (B) diet with 1% cholesterol deficient in both selenium and vitamin E (B+cho diet) or identical diets to which either vitamin E (B+E+cho) or selenium (B+Se+cho) or both micronutrients were added (B+Se+E+cho). Plasma-cho and lipoprotein-cho levels were measured after 6, 12, 16, and 18 weeks of feeding the experimental diets. Rats fed the B+cho diet for at least 12 weeks had plasma-cho levels about twice that observed for rats fed the B+E+Se+cho diet. Plasma-cho levels for rats in the two Se deficient groups (B+cho and B+E+cho) were, however, similar at any time point. Se deficiency was associated with increased plasma-cho, very low density lipoprotein-cho (VLDL-cho) and low-density lipoprotein-cho (LDL-cho). Vitamin E supplementation interacted with Se deficiency to increase plasma VLDL-cho levels. Neither vitamin E alone nor the interaction between vitamin E and Se consistently influenced LDL-cho levels. The percent cholesteryl ester in LDL from rats fed the Se-deficient diets (B+cho or B+E+cho) was at least twice that observed for rats fed the B+E+Se+cho diet. Plasma lipid peroxidation products were highly elevated in rats fed the B+cho diet compared with values for the B+E+cho or the B+E+Se+cho fed rats (which were not significantly different). These results suggest that dietary Se deficiency increases plasma-cho, VLDL-cho, and LDL-cho levels by a mechanism that may be unrelated to its role as an antioxidant nutrient. PMID- 8208737 TI - Daily exposure to a nonphotic stimulus can alter photoperiodic response to short days in hamsters. AB - The ability of mammals to measure seasonal changes in daylength depends upon a circadian clock and the phase-relationship between this clock and the light: dark cycle. Recently, a number of pharmacological and nonpharmacological stimuli have been shown to have pronounced effects on the phase of the circadian clock of rodents. The objective of the present study was to determine if a drug-induced change in the phase-relationship between a measurable circadian rhythm (i.e., wheel running behavior) and the light:dark cycle would alter the effects of the light cycle on the neuroendocrine-gonadal axis. Adult male hamsters with regressed testes due to exposure to an inhibitory 10:14-hr light:dark cycle were daily injected with vehicle or the short-acting benzodiazepine, triazolam, while remaining on short days, while a control group of hamsters was transferred to a photostimulatory 14:10-hr light:dark cycle. Two other groups of hamsters with regressed testes were blinded and daily injected with vehicle or triazolam. The injections were timed to occur about 4 hr before activity onset because previous studies had demonstrated that injections of triazolam at this time can lead to a phase advance in the activity rhythm. The circadian rhythm of wheel running behavior was measured in all the animals maintained on the 10:14-hr light:dark cycle in order to monitor circadian phase. While no testicular growth was observed after 25 days of vehicle injections, growth was observed in the triazolam-treated animals that was comparable to that observed in control animals transferred to long days. Testicular growth in triazolam-treated animals was associated with an earlier onset of locomotor activity, when compared with the vehicle-treated animals. Importantly, triazolam had no effect on the testicular size of blind animals. These results indicate that daily injections of triazolam can stimulate neuroendocrine-gonadal activity by altering the phase-relationship between the cycle and the circadian clock involved in photoperiodic time measurement, and that agents which can affect the clock may be useful in altering seasonal cycles. PMID- 8208739 TI - Establishment of a turkey cecal cell line and development of turkey coccidia within the cells. AB - Cells were dispersed from cecal tissues of 1- to 2-day-old turkeys using a mixture of collagenase and dispase to enrich for epithelial cells. The initial culture produced from these cells (TCC) appeared to be heterogeneous, but, as the cells were cultured through 25 passages, they assumed a more fibroblastic appearance. Cellular invasion of the TCC by two species of turkey coccidia, Eimeria adenoeides and Eimeria meleagrimitis, was not enhanced, as compared with invasion in turkey kidney cells (TKC), the cell culture system standardly used to study the avian coccidia in vitro. However, early development by one of the species, E. meleagrimitis, was markedly increased in the TCC (Passages 6 through 19) over that in TKC. Thirty to 42% of the parasites that invaded the TCC developed beyond the sporozoite stage, as compared with 5% development in TKC. Mature first-generation schizonts were observed within 24 hr postinoculation in the TCC, but not until 48 hr in the kidney cells. There was no evidence that development of the second generation was initiated in either the TCC or kidney cells. PMID- 8208738 TI - Pancreatic islet cells in preobese yellow Avy/- mice: relation to adult hyperinsulinemia and obesity. AB - Plasma insulin levels in yellow Avy/- mice begin to increase before the animals are overtly obese. Are the elevated insulin levels in yellow mice primary or secondary to the subsequent obesity? Elevated blood insulin levels in young preobese mice, due to synthesis and release of insulin by increased number of beta cells, would stimulate lipogenesis, resulting in excess lipid deposition and subsequent peripheral insulin resistance. Examination of this possibility was the objective of this study. The beta, alpha, and delta cells in the pancreata of 7-, 14-, and 21-day-old male yellow Avy/A and agouti A/a (BALB/c x VY)F1 hybrid mice were counted with immunohistochemical/morphometric techniques. The insulin and glucagon concentrations in pancreata from male and female mice of the same ages and genotypes were also assayed. In the 21-day-old male mice, the mean number of beta cells/pancreas was significantly greater in the yellow mice than in the agouti mice; however, insulin content and body weight were the same. This suggests that increased beta cell proliferation in yellow mice precedes any detectable genotype-specific increase in pancreatic insulin content or body weight. PMID- 8208740 TI - Dietary supplementation of L-arginine ameliorates renal hypertrophy in rats fed a high-protein diet. AB - Ingestion of a high-protein diet or intravenous administration of amino acids is associated with an increase in glomerular filtration rate (GFR). It can also lead to renal hypertrophy, and, if sustained, may cause glomerular sclerosis. L Arginine administration ameliorates the progression of renal disease in rats with subtotal nephrectomy and prevents the increase in GFR observed in rats with experimental diabetes. The present study examines the potential effect(s) of L arginine administration (1%) in the drinking water on the renal hypertrophy that occurs in rats fed a high-protein diet for 1 month. Four groups of female Sprague Dawley rats, six in each group, were studied (95 +/- 1 g). Groups 1 and 2 were fed a low-protein diet (12% casein, 0.504% L-arginine); Group 1 was given tap water, whereas Group 2 was given tap water supplemented with L-arginine. Groups 3 and 4 were fed a high-protein diet (40% casein, 1.68% L-arginine); Group 3 was given tap water, whereas Group 4 was given tap water supplemented with L arginine. The rats had free access to food and water during the study period. The kidney weight and the kidney to body weight ratio of rats of Group 3 were significantly greater than in the other groups of rats. Renal hypertrophy was prevented in the rats of Group 4. The excretion of orotic acid in the urine, an index of L-arginine deficiency, was significantly greater in rats of Group 3 than in rats of Group 4. Thus, the renal hypertrophy that occurs in rats fed a high protein diet was decreased in rats given L-arginine supplementation in the drinking water. This effect was associated with less excretion of orotic acid in the urine in rats given L-arginine. A relative deficiency of L-arginine may occur during high-protein feeding that may shunt nitrogen metabolism from the urea cycle to the orotic acid pathway. PMID- 8208741 TI - RNA transcription in porcine skeletal muscle nuclei during postnatal development. AB - Postnatal developmental pretranslational regulation of skeletal muscle alpha actin gene expression was investigated. Northern blot analysis of skeletal muscle alpha-actin and beta-tubulin mRNA from 1- and 28-day-old pigs indicated that there are developmental increases in alpha-actin mRNA abundance (P < 0.03) and no significant changes in beta-tubulin mRNA (P > 0.1). A system for isolation of nuclei from porcine skeletal muscle and for transcriptional "run-on" analysis was established in order to investigate the regulatory mechanism of developmental changes in porcine skeletal muscle protein. Skeletal muscle nuclei were isolated from longissimus dorsi (LD) muscle of 1- and 28-day-old pigs by adapting a method to isolate nuclei from cardiac muscle. Results from a [3H]-UTP incorporation assay indicate that these nuclei preparations have the capacity to synthesize RNA and attain maximum incorporation after 40-45 min at 26 degrees C. Messenger RNA syntheses from skeletal muscle nuclei from 1- and 28-day-old pigs were not significantly different (P > 0.25). All nascent tRNA, rRNA, and mRNA in the nuclei were elongated since [3H]-UTP incorporation was reduced after addition of 0.05 micrograms/ml alpha-amanitin to the transcription mixture. Transcription "run-on" assay results indicated that more (P < 0.02) skeletal muscle alpha-actin pre-mRNA was synthesized in the 28-day-old pig skeletal muscle nuclei than in the 1-day-old pig skeletal muscle nuclei. These results indicate that the relative increase in skeletal muscle alpha-actin mRNA observed in the older animals was due, at least in part, to an increase in the transcriptional activity of the skeletal muscle alpha-actin gene. PMID- 8208742 TI - Insulin-like growth factors and bone: the osteoporosis connection. AB - In the last five years significant progress has been made defining the role of insulin-like growth factors (IGFs) in the process of bone remodeling. In this paper, we present critical evidence that IGF-I and IGF-II are produced by bone cells and regulate specific osteoblastic and osteoclastic functions. In addition, we review work from several laboratories establishing the role of the skeletal IGF binding proteins as an integral component of a unique IGF regulatory system. Data presented suggest that the calciotropic hormones active in the bone remodeling process may exert their effects through the IGF regulatory system. In contrast to the well-defined local action of IGF-I and IGF-II on the skeleton, the relationship between circulating IGF-I and bone remodeling is less certain. Newer data are presented which suggest the potential utility of serum growth factor measurements in certain clinical states. Finally, this paper presents an overview of the most current efforts to stimulate bone formation using recombinant IGFs. However, work on the beneficial aspects of IGFs for the skeleton remains preliminary at best with the eventual therapeutic role of IGF-I in osteoporosis yet to be defined. PMID- 8208743 TI - The modelling of beta 2-adrenergic receptors. AB - Adrenergic mimetics have many varied pharmacological applications, thus the quest for selective and efficacious ligands. Provided that a reasonable receptor model can be constructed which mimics the key interactions between a ligand and its biological receptor, molecular modelling offers the potential for rational drug design. The beta 2-adrenergic receptor models reviewed in this article have increased in sophistication, in line with more information becoming available about the residues involved in ligand binding, as well as the topography of the receptor. PMID- 8208744 TI - Flavonoids from Iochroma gesnerioides. AB - Two aglycones (kaempferol and quercetin) and three glycosides (isoquercitrin, kaempferol 3-sophoroside and quercetin 3-sophoroside) were isolated from Iochroma gesnerioides (Kunth) Miers (Solanaceae). Whereas the aglycones are common for the Solanaceae, their 3-sophorose derivatives are found only in three genera of this family. Their isolation and identification (mainly by 1H- and 13C-nmr) are reported here. PMID- 8208745 TI - Comparative in vitro diffusion studies for atenolol transdermal delivery system. AB - The purpose of this study was to screen atenolol as a candidate for transdermal drug delivery, and to study the release of atenolol from various gels. The percent atenolol release over time profiles indicates that for all the gelling agents used the amount of atenolol released is decreased by increasing the polymer concentration in the gel. The amount of atenolol released was found to be higher from Klucel gels, compared to Methocel and Carbopol gels, with Carbopol gels giving the least release. In studying the effect of atenolol concentration in the gel, it was observed that the amount of atenolol released was increased by increasing the drug concentration in the donor up to a limit corresponding to an atenolol concentration of approximately 2%. This seems to resemble the saturation solubility of atenolol into the gels. Hairless mouse skin and TESTSKIN LSE were used as in vitro skin models. PMID- 8208746 TI - A new pharmophoric model for 5-HT reuptake-inhibitors: differentiation of amphetamine analogues. AB - A pharmacophoric model for 5-HT reuptake-inhibitors was developed using the pharmacophore elements geometry and MEP (Molecular Electrostatic Potential) by the method of active analogue approach. This model is characterized by: (1) a protonated basic nitrogen separated by 610 pm from the center of an aromatic system and 920 pm from an electronegative substituent of this aromatic system, (2) a region with n- and/or pi-electrons along the axis substituent-aromatic system-nitrogen atom, (3) an aliphatic side chain which joins the region of the n and/or pi-electrons with the nitrogen atom, (4) an additional aromatic group at right angles to the pharmacophoric aromatic group below the protonated nitrogen and (5) a forbidden region on the pharmacophore which leads to a deviation of the allowed tubular orientation of the ligand. The pharmacophore model enables a differentiation of the entactogenic, hallucinogenic and stimulating arylalkanamines. The theoretical considerations are confirmed by a postulated intramolecular H-bonding in the active conformation of the selective 5-HT reuptake-inhibitor, citalopram (12 in Fig. 2), which could be proved by NMR- and IR-spectroscopic measurements. PMID- 8208747 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 8208748 TI - The role of platelet-activating factor in the pathogenesis of gastrointestinal disease. PMID- 8208749 TI - Is the antiatherosclerotic potency of HDL modulated by the origin of HDL? AB - Different HDL preparations from rabbit blood were injected intravenously (10 mg HDL protein/injection and animal) into cholesterol fed rabbits twice a week for 8 weeks. The composition of the used high density lipoprotein (HDL) was modified by dietary pretreatment. HDL-1 was taken from rabbits after 8 weeks pellet diet, HDL 2 after 8 weeks fish-oil rich diet and HDL-3 after 8 weeks of cholesterol rich diet. The animals treated with HDL-1 and HDL-2 had a significantly smaller area of intima covered with fatty streaks than the control animals (injection of saline instead of HDL). The injection of HDL-3 was without influence. These differences were correlated with changes in the level of free and esterified cholesterol (FC and CE) in kidney, liver and aorta of the rabbits, but not with the level of cholesterol in the serum lipoproteins. We investigated simultaneously the influence of the different HDL preparations on the cholesterol content in rabbit skin fibroblasts (RSF), rabbit smooth muscle cells (SMC) and human hepatoma cell line Hep G2. Additionally the influence on the proliferation of SMC was studied. HDL-1 diminished the level of FC in cholesterol enriched RSF and rabbit SMC, whereas both other HDL preparations had no effect. The level of FC in Hep G2 was not influenced. HDL-1 and HDL-3 stimulated the proliferation of rabbit SMC, whereas HDL-2 had no such influence. The data support the antiatherosclerotic role of HDL injections in cholesterol fed rabbits, but the composition of the used HDL seems to modify this influence, probably by different effects on the biochemical changes induced by the HDL. PMID- 8208750 TI - Interrelationship of ascorbate, arachidonic acid and prostaglandin E2 in B16 melanoma cells. AB - Previous studies have shown that ascorbate (Asc) supplementation affects arachidonic acid (AA) and prostaglandin E2 (PGE2) levels in B16 murine melanoma cells. In this study, non-malignant LLCMK cells and malignant B16 cells were respectively supplemented with 20 microCi 15-3H AA, to investigate whether these two cell types were able to take up AA from the media. Furthermore, these cells were also supplemented with Asc (0-100 micrograms/ml) to determine the effect of Asc supplementation on 15-3H AA uptake. Both cell types incorporated 15-3H AA, while Asc supplementation enhanced this 15-3H AA uptake. To determine the site of the AA incorporation, both cell types were supplemented with 2.5 microM AA and Asc (0-100 micrograms/ml). The % AA composition of the stroma fractions of both cell types was increased with 100 micrograms/ml Asc supplementation. Supplementation of these cells with AA (0-50 microM) resulted in an increase in PGE2 levels in the B16 cells. Since PGE2 has been shown, in turn, to stimulate adenylate cyclase (AC) activity, the LLCMK and B16 cells were supplemented with 0 100 microM PGE2. A 3-fold increase of AC activity in the B16 cells occurred as a result of this supplementation. PMID- 8208751 TI - Actions of interleukin-4 on prostaglandin biosynthesis by human amnion cells. AB - The effects of interleukin-4 (IL-4) on amnion prostaglandin (PG) production have been determined. Human amnion cells from term placentae were grown to confluence and incubated with IL-4 either alone or with various concentrations of epidermal growth factor (EGF) of ionomycin. PGE2 production was determined using a specific radioimmunoassay. IL-4 alone stimulated PGE2 production in amnion cells in a concentration-related manner. IL-4 significantly enhanced the stimulatory actions of ionomycin and EGF on amnion cell PGE2 production. Ionomycin and IL-4 acted synergistically in their effects on PGE2 production by amnion cells whereas EGF and IL-4 acted more additively in this respect. We suggest that IL-4 production by immune effector cells in gestational tissues may contribute to the mechanisms of labor at term and preterm. PMID- 8208752 TI - Regulation of intrauterine prostaglandin biosynthesis: interactions between protein kinase C and interleukin 1 beta. AB - Activation of protein kinase C with phorbol esters stimulates prostaglandin (PG) biosynthesis in many cell types whereas down-regulation of protein kinase C can suppress stimulatory responses. Interleukin-1 beta (IL-1 beta) can stimulate PG production by intrauterine tissues and may play a significant part in the mechanisms of preterm labor associated with intrauterine infection. Hence we have evaluated the effects of staurosporine and H7 (inhibitors of protein kinase C) on IL-1 beta stimulation of amnion, chorion and decidual prostaglandin E2 (PGE2) production. Staurosporine and H7 alone were without effect on PGE2 production by any cell type. However with minor exceptions both protein kinase C inhibitors enhanced the stimulatory actions of IL-1 beta on PGE2 production by all three cell types. Hence we believe that protein kinase C is closely linked to the regulation of intrauterine PG biosynthesis and that these links may have multiple layers of complexity. PMID- 8208753 TI - Prostaglandin E2 production in submandibular salivary glands of rats in essential fatty acid deficiency. AB - Three groups of rats were fed an essential fatty acid (EFA)-deficient diet (EFAD), marginally EFA-deficient diet (MEFAD) or a control diet. Arachidonic acid levels in total phospholipids and the ex-vivo production of prostaglandin E2 (PGE2) in the presence of calcium ionophore were measured at 5 and 9 weeks in the submandibular salivary glands (SMSG). The arachidonic acid levels were significantly different among the 3 groups of rats fed the respective diets for 9 weeks. Ex-vivo PGE2 production was significantly decreased in the EFAD group but not in the MEFAD group as compared to the control group. The changes in fatty acid composition, arachidonic acid levels and ex-vivo production of PGE2 were reversed after 5 weeks of feeding the control diet to the EFAD or the MEFAD rats. Since arachidonic acid and PGE2 are involved in signal transduction pathways in the SMSG, an EFA deficiency is likely to modify these pathways. PMID- 8208754 TI - Essential fatty acid deficiency in the pig: effects on eicosanoid basal levels and in vitro synthesis by the small intestine. AB - The influence of nutritional essential fatty acid (EFA) deficiency on arachidonate metabolism by porcine small intestine has been studied. Great care was exercised in the manipulation of the jejunal wall to avoid artefactual metabolism of arachidonate. Thus, jejunal wall was frozen in liquid nitrogen after organ removal and washing, and subsequently lyophilized. This lyophilized tissue was used as starting material for all experiments, including organic solvent extractions (for basal level determinations) and reconstitution in aqueous buffer (for neosynthesis experiments). Feeding pigs with a low linoleate diet for 12 weeks resulted in a 36% diminution in the % of arachidonate in jejunal phospholipids. Basal levels of 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), thromboxane B2 (TXB2), PGF2 alpha, PGE2, PGD2 and leukotriene B4 (LTB4) were not altered in the EFA-deficient state. However, we observed a significant lowering of the synthesis of each of these eicosanoids (except LTB4) by the EFA deficient jejunum during brief (15s) in vitro neosynthesis experiments. The origin of arachidonate as a substrate of PG endoperoxide synthase, also named PGH synthase or cyclooxygenase (Cox) in these neosynthesis experiments is probably a non-esterified fatty acid pool since, (1) neosynthesis was not inhibited by the phospholipase A2 (PLA2) inhibitor parabromophenacylbromide, and (2) substantial amounts of arachidonic acid were found in the jejunum, frozen or lyophilized. Cox activity of the lyophilized jejunum and Cox content of liver and intestine microsomes were not modified in the EFA-deficient state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208755 TI - The reduction in alcohol drinking by peripherally injected angiotensin II is selectively mediated by the AT1 receptor subtype. AB - We investigated which of the two angiotensin (ANG) receptor subtypes mediates the reduction in alcohol intake produced by peripheral injections of ANG II. Adult male Wistar rats were trained to self-administer alcohol (6% w/v) using a procedure that, by limiting access to a brief daily availability period (40 min), fosters a bout pattern of alcohol drinking and a pharmacodynamic effect. Water was continuously available. Once intake stabilized, groups received daily injections either 200 micrograms/kg ANG II SC or the control vehicle saline immediately prior to alcohol availability. Alcohol consumption was attenuated and water intake elevated in the groups receiving ANG II and was unaffected by the vehicle injections. Following this, different groups were pretreated with ascending doses (0.25, 0.5, 1.0 mg/kg) of either PD123319, the selective AT2 receptor antagonist, Sar1,Thr8-ANG II (0.25 mg/kg), the nonselective ANG II antagonist, or DuP753 (0.25, 0.5, 1.0 mg/kg), the selective AT1 receptor antagonist. Control groups received antagonist pretreatment followed by the ANG II vehicle. Neither PD123319, DuP753, or Sar1, Thr8-ANG II had any effect of their own on alcohol or water intake. Pretreatment with PD123319 did not alter the suppressive effect of ANG II on alcohol intake. DuP753 produced a dose dependent attenuation in the suppressive effect of ANG II on alcohol intake and antagonized the dipsogenic effect of ANG II on water intake. The effect of Sar1,Thr8-ANG II was similar to that of DuP753. These findings suggest that the reduction in alcohol intake produced by ANG II is mediated through the AT1 receptor subtype. PMID- 8208756 TI - Corticotropin-releasing factor and schedule-induced polydipsia. AB - Two experiments examined the effects of ICV-administered corticotropin-releasing factor (CRF) and alpha-helical CRF (9-41), a CRF antagonist, on the performance of schedule-induced polydipsia (SIP). Infusions of CRF into the lateral ventricle dose-dependently (0.02, 0.1, and 0.5 micrograms) attenuated both the volume of water consumed and licking on a fixed-time 60-s schedule. This effect of CRF on schedule-induced drinking was accompanied by a reduction in the number of nose pokes made into the food tray, suggesting that CRF may attenuate SIP through an action on appetitive motivation. Neither the temporal distribution of responding nor the locomotor activity induced by the schedule was affected by CRF. In marked contrast to these effects of exogenous CRF on the performance of SIP, infusions of alpha-helical CRF (1, 5, and 25 micrograms) into the lateral ventricle did not affect the performance of schedule-induced polydipsia. The implications of these results for the hypothesis that SIP is a coping response to stress are discussed. PMID- 8208757 TI - 5-HT3 receptor modulation of behavior during withdrawal from continuous or intermittent cocaine. AB - The present experiments examined alterations in 5-HT3 receptors during withdrawal from continuous or intermittent cocaine. Rats were pretreated with 40 mg/kg/day cocaine for 14 days by either SC injections or osmotic minipumps. The rats were then withdrawn from the pretreatment regimen for 7 days. In Experiment 1, rats received 0-16 mg/kg IP injections of ondansetron, a selective 5-HT3 receptor antagonist. In Experiment 2, the rats received 0-16 mg/kg IP ondansetron in combination with a 15 mg/kg IP injection of cocaine. In Experiment 3, the subjects received 0-16 mg/kg IP injections of ondansetron in combination with a 7.5 mg/kg IP injection of cocaine. Following these injections, the subjects' behavior was rated using the Ellinwood and Balster (18) rating scale. The results of Experiment 1 indicated that ondansetron had no effect on the behavior of the subjects, nor was there a differential effect of pretreatment regimen the effects of ondansetron. The results of Experiment 2 indicated that ondansetron had no effect on cocaine-induced locomotion in the saline control rats, but did have a slight, statistically significant, suppressive effect in the injection rats. In contrast, ondansetron had a robust facilitative effect on cocaine-induced locomotion in the continuous infusion rats. The results of Experiment 3 indicated that ondansetron had no effect on cocaine-induced locomotion in the saline control rats or the cocaine injection pretreatment subjects. In the continuous infusion subjects, ondansetron did have a slight, statistically significant, facilitative effect on cocaine-induced locomotion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208758 TI - Potassium, rubidium, and 4-aminopyridine effects on the circadian running rhythm in the hamster. AB - The period of the circadian rhythm of wheel-running was shortened when golden hamsters were given supplemental dietary potassium or rubidium for two weeks. Treatment with 4-aminopyridine, a potassium channel blocker, significantly increased circadian period. These period changes (0.17 h for potassium treatment, 0.14 h for rubidium, and 0.07 h for 4-aminopyridine) support previous data indicating that potassium is a component of the mammalian biological clock mechanism. PMID- 8208760 TI - Effects of chronic imipramine on exploration, locomotion, and food/water intake in rats. AB - Three groups of rats were subjected to 15 daily injections of imipramine (10 or 20 mg/kg) or vehicle control injections, respectively. During the treatment period, both imipramine groups failed to grow while the control group gained weight normally. Both dosages of imipramine suppressed food intake significantly, while water intake was only reduced by 20 mg/kg of imipramine and only during the first 5 days of treatment. Twenty-four hours after the last imipramine injection, the animals were subjected to a test battery designed to demonstrate potential changes in locomotion and/or exploration. While locomotion appeared unaffected by both dosages of imipramine, the group receiving 20 mg/kg of imipramine demonstrated a significantly reduced exploration. The exploration of the group receiving imipramine in the concentration of 10 mg/kg was only marginally changed. The temporal pattern of exploration of the animals receiving 20 mg/kg of imipramine revealed that chronic imipramine treatment was associated with an initial "hyperexploration" followed by an "overhabituation," resulting in an overall reduction of exploration during a 15-min period. PMID- 8208759 TI - Amphetamine-induced modification of quinine palatability: analysis by the taste reactivity test. AB - The effects of low doses of d-amphetamine (0.25-0.5 mg/kg, IP) on taste reactions elicited by quinine solutions in a 5-10-min taste reactivity test were assessed in a series of three experiments. Amphetamine consistently suppressed aversive reactions elicited by quinine solutions. The results suggest that amphetamine, like morphine, attenuates the aversiveness of the taste of quinine solution. PMID- 8208761 TI - Effects of dizocilpine in withdrawal seizure-prone (WSP) and withdrawal seizure resistant (WSR) mice. AB - Mice selectively bred to be Withdrawal Seizure-Prone (WSP) or Seizure-Resistant (WSR) after chronic ethanol administration have been reported to be differentially sensitive to the anticonvulsant and proconvulsant effects on alcohol withdrawal of drugs interacting with glutamate receptors. Several behavioral effects of the noncompetitive glutamate receptor antagonist, dizocilpine, were determined in WSP and WSR mice to see whether their differential sensitivity generalized to effects unrelated to seizures, and to see whether it was only apparent during ethanol withdrawal. Dizocilpine potentiated the loss of righting reflex induced by ethanol, and dose-dependently stimulated habituated and nonhabituated open field activity. WSP and WSR mice were equally sensitive to these effects of dizocilpine. Pretreatment with dizocilpine increased the transcorneal amperage necessary to produce maximal electroshock seizures: WSR mice were more sensitive than WSP to this effect. Ethanol withdrawal (i.e., testing 6 h after a 24-h exposure to ethanol vapor) and dizocilpine had several effects on mice tested in the hole-in-wall apparatus. Several differences between WSP and WSR mice were also found, but in no case did dizocilpine differentially affect ethanol-withdrawing WSP and WSR mice. Across these experiments, differences between WSP and WSR mice in response to dizocilpine were rather specific. For some responses, WSP and WSR mice were equally sensitive, but only in the seizure-related measure assessed were naive WSR mice more sensitive than WSP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208762 TI - Continuous or intermittent cocaine administration: effects of amantadine treatment during withdrawal. AB - Research indicates that daily cocaine injections produce sensitization to, while the continuous infusion of cocaine produces tolerance to, its behavioral and neurochemical effects. The effects of the continuous infusion of cocaine are consistent with the withdrawal syndrome reported by human cocaine abusers. The present experiment examined whether amantadine administrations during withdrawal from continuous or intermittent cocaine attenuate and/or eliminate the behavioral effects produced by these administration regimens. The rats were pretreated for 14 days with either continuous or intermittent daily injections of cocaine, and were then withdrawn from the pretreatment regimen for 7 days. On days 1-5 of the withdrawal period, half the subjects received a 5.0 mg/kg IP injection of amantadine, and the other half received a 20.0 mg/kg IP injection of amantadine. On day 7 of withdrawal from the cocaine pretreatment, all rats were given a 15.0 mg/kg IP injection of cocaine. Their behavior was rated according to the modified Ellinwood and Balster (6) scale for 60 min. The results indicated that amantadine treatment during withdrawal eliminated the tolerance normally associated with the continuous infusion of cocaine. In contrast, in both the saline control and daily injection subjects amantadine treatment during withdrawal resulted in a slight, but statistically significant, reduction in the behavioral effects of cocaine. The present results therefore indicate that low doses of amantadine should be considered as a potential pharmacotherapy for the early stages of cocaine withdrawal. Furthermore, the present experimental procedures may represent an effective screening methodology for potential cocaine pharmacotherapies. PMID- 8208763 TI - Hypothalamic infusion of the 5-HT2/1C agonist, DOI, prevents the inhibitory actions of the 5-HT1A agonist, 8-OH-DPAT, on lordosis behavior. AB - Sexually receptive, intact, proestrous rats were infused bilaterally into the ventromedial nucleus of the hypothalamus (VMN) with 200 ng of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), with 2000 ng of the 5-HT2/1C agonist, (+/-)-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), or with both 8-OH-DPAT and DOI. Alone, VMN infusions of 8-OH-DPAT, but not DOI, inhibited lordosis behavior. When 2000 ng DOI was infused simultaneously with 8-OH-DPAT, the inhibitory effects of 8-OH-DPAT were completely abolished. These results suggest that neural sites responsible for the reported facilitatory effects of 5 HT2/1C agonists on lordosis behavior coexist in the VMN with those sites in which 5-HT1A agonists are effective in reducing lordosis behavior. In contrast to the protective action of the 5-HT2/1C receptor agonist following VMN infusion, no protection was seen when both DOI and 8-OH-DPAT were administered intraperitoneally. Thus, the interaction of these two receptor subtypes in the control of lordosis behavior may be different in regions outside the VMN. PMID- 8208764 TI - Failure of triazolam to alter circadian reentrainment rates in squirrel monkeys. AB - The short-acting benzodiazepine triazolam has been shown to cause phase-dependent phase shifts of the circadian activity rhythms of squirrel monkeys maintained in constant light. The present study sought to determine whether properly timed triazolam administration can also accelerate the reentrainment of circadian rhythms following phase shifts of the daily light-dark (LD) cycle. Circadian rhythms of telemetered body temperature and locomotor activity were recorded from squirrel monkeys exposed to an 8-h phase advance of the LD cycle, followed 16 days later by an 8-h phase delay. On the day of the phase advance, each animal received a single injection of triazolam (0.3 mg) or of vehicle alone in midsubjective day (circadian time 6 [CT6], where CT0 represents the time of light onset and the beginning of subjective day, and CT12 the time of dark onset and the beginning of subjective night]), 2 h after the new time of dark onset, while on the day of the phase delay the animals received triazolam or vehicle in late subjective night (CT20), just before dark onset. This procedure was then repeated, giving triazolam to animals that had previously received vehicle alone, and vehicle to animals that had received triazolam. The daily acrophases of the temperature and activity rhythms were calculated by cosinor analysis, and exponential functions were fitted to the acrophases that followed each of the phase shifts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208765 TI - NS-3, a TRH analog, reverses repeated ECS-induced deficits in water maze performance in the rat. AB - Rats given five consecutive daily electroconvulsive shock (ECS) treatments and trained to run in the Morris water maze, starting three days posttreatment, showed deficits in learning and memory functions. Treatment before each training session with the thyrotropin-releasing hormone (TRH) analog NS-3 [(CG-3703), (3R),(6R)-6-methyl-5-oxo-3-thiomorphorinyl-l-histidyl-l-prolinamid e tetrahydrate] reversed these behavioral deficits. The possible use of TRH and its analogs as therapeutic treatment for the cognitive dysfunctions resulting from electroconvulsive shock treatment for depression and the possible involvement of central cholinergic systems in the cognitive dysfunctions are discussed. PMID- 8208766 TI - Assessing spiradoline-like discriminative effects of DuP 747: influence of route of administration. AB - DuP 747, trans-3,4-dichloro-N-methyl-N-[2-(pyrrolidin-1-yl)-1,2,3,4- tetrahydronaphthalen-1-yl]benzeacetamide methanesfonate, is a recently synthesized analgesic drug that binds with high affinity and selectivity to the kappa-opioid receptor. In order to determine if DuP 747 has kappa-like discriminative effects it was tested for stimulus generalization in rats trained to discriminate between SC injections of saline and 3.0 mg/kg of spiradoline, a potent kappa-opioid agonist. A range of drug doses was administered by each of several routes 30 min before a test session. Spiradoline occasioned orderly dose dependent increases in spiradoline-appropriate lever selection after SC or IP administration, with ED50s of 0.65 and 1.75 mg/kg, respectively. In contrast, DuP 747 (1.0-30 mg/kg) occasioned little spiradoline-appropriate lever selection when administered SC, but was generalized from spiradoline partially when administered IP (ED50 = 5.9 mg/kg) or PO (ED50 = 59 mg/kg). The 5-hydroxy-desmethoxy metabolite of DuP 747, administered SC (0.3-10 mg/kg), occasioned selection of the saline-appropriate lever only. That DuP 747 had little spiradoline-like activity after SC administration suggests that a metabolite of DuP 747 was responsible for the spiradoline-appropriate responding that followed IP and PO administration of the drug, apparently a metabolite other than 5-hydroxy desmethoxy-DuP 747. PMID- 8208767 TI - Influence of change from grouped to individual housing on a T-cell-dependent immune response in mice: antagonism by diazepam. AB - Transferring CD-1 mice from grouped to individual housing and then maintaining them individually resulted in a decline in the peak IgM plaque-forming cell (PFC) response to sheep red blood cells (SRBCs). However, the immunosuppression was dependent on the amount of time mice were maintained individually. In particular, individual housing for 5-10 days prior to SRBC inoculation and for 4 days following inoculation resulted in a suppression of the splenic PFC response and serum antibody titers. Shorter periods of individual housing (4 days following inoculation) did not provoke the immunosuppression. Likewise, following more protracted individual housing (15-30 days prior to inoculation) the immunosuppression was not evident. Inasmuch as daily treatment with an anxiolytic, diazepam (1.0 mg/kg), antagonized the suppression induced by 5 days of individual housing, it was suggested that the change from group to individual housing and then maintenance of animals individually acted much like a stressor to induce the immunosuppression. PMID- 8208768 TI - Evidence for specific interactions between 5-HT1A and dopamine D2 receptor mechanisms in the mediation of extrapyramidal motor functions in the rat. AB - Administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n propylamino)tetralin (8-OH-DPAT; 0.1 mg kg-1 SC) completely antagonised the catalepsy produced by the dopamine (DA) D2 receptor antagonist raclopride (16 mg kg-1 SC). This effect by 8-OH-DPAT was in turn completely antagonised by treatment with the new 5-HT1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(di-n propylamino)tetralin [(S)-UH-301] (3.5 mg kg-1 SC), but not by the mixed 5-HT1 receptor/beta-adrenoceptor antagonist (-)pindolol (2.0 mg kg-1 SC). The failure by (-)pindolol to antagonise the effects of 8-OH-DPAT on raclopride-induced catalepsy could be due to its beta-receptor-blocking properties, since by themselves both (-)pindolol and the selective beta-adrenoceptor antagonist betaxolol (4 mg kg-1 SC) at least partially antagonised the raclopride-induced catalepsy. The present results provide further support for specific interactions between 5-HT1A and DA D2 receptor mechanisms in the mediation of extrapyramidal motor functions in the rat. PMID- 8208769 TI - Differential sensitivity of operant behaviors to changes in the concentration of a sucrose reinforcer: effects of pimozide. AB - The sensitivity of operant response rates to changes in a sucrose reinforcer was examined in well-trained animals maintained on a variable ratio (VR) or variable interval (VI) schedule (experiment 1). Although VR performance showed greater resistance to small reductions in the concentration of the sucrose reinforcer than VI performance, VR performance was more sensitive to large reductions in the sucrose concentration. Despite this differential sensitivity only the smallest dose of pimozide (0.125 mg/kg) differentially affected these behaviors by reducing VI rates without affecting VR rates. These and other results support the view that low doses of pimozide reduce the hedonic impact of the reinforcer. The results also indicate that the attenuation of operant responding by higher doses (0.25, 0.5, and 1.0 mg/kg) cannot be solely a result of the blunting of reward. Experiment 2 demonstrated that when rats drink in daily, brief one-bottle tests they show greater resistance to reductions in the sucrose concentration than when they lever-press for sucrose, and require a higher dose of pimozide (2.0 mg/kg) to attenuate consumption. Together the results of both experiments suggest that the greater the resistance to reductions in the reinforcement value, the greater the dose of pimozide necessary to attenuate performance. We discuss the importance of attaining a more complete understanding of the factors in control of operant performance in order to better assess the effects of neuroleptics on reward. PMID- 8208770 TI - Nitrous oxide: sensory, motor, associative, and behavioral tolerance effects in classical conditioning of the rabbit nictitating membrane response. AB - Experiment 1, of a series of six experiments with the rabbit nictitating membrane response (NMR) preparation, revealed that nitrous oxide (0%, 33%, 67%) impaired acquisition of conditioned responses (CRs). Subsequent experiments indicated that nitrous oxide (N2O) had no reliable effects upon nonassociative processes (Experiment 2); impaired unconditioned response (UR) amplitude (Experiment 3); attenuated tone-conditioned stimulus (CS) intensity (Experiment 4); decremented tone-induced reflex modification of the unconditioned NMR (Experiment 5); and demonstrated no reliable evidence of behavioral tolerance (Experiment 6). It was concluded that N2O's impairment of CR acquisition was attributable to its attenuation of the intensity of tone CSs and shock USs and/or UR amplitude. These findings are consistent with the behavioral laws of conditioning: the attenuation of the intensive sensory properties of the CS and US and/or UR components of conditioning affect their ability to enter into the establishment of CS-CR connections and, therefore, the development of associative learning. PMID- 8208771 TI - Methodological issues in the administration of multiple doses of smoked cocaine base in humans. AB - Many methodological issues exist in human laboratory research with smoked cocaine base that include safety, precision of dose delivery of smoked cocaine, and the lack of an adequate placebo. All of these issues are particularly apparent with studies involving multiple doses of cocaine. Addressing these concerns is important in conducting parametric studies that require examining dose-response effects. The purposes of this study were to determine: 1) the safest interval between doses to deliver smoked cocaine; 2) the accuracy or reproducibility of administering precise and multiple doses of cocaine; 3) the potential for using a control dose of cocaine; and 4) the influence of multiple doses on these parameters. Six black males were given 10 doses of either 5 or 35 mg of cocaine base at 15-, 30-, and 45-min intervals. The dependent measures included physiological, subjective, and performance responses. These measures were taken prior to dosing and at specific time intervals after each dose of smoked cocaine. The results showed: 1) dosing at 30-min intervals allowed sufficient time for recovery of blood pressure and heart rate to permit up to 10 doses to be safely administered; 2) reproducible blood cocaine levels were obtained with repeated dosing using a heated wire-coil device; 3) significant differences were observed between the 5- and 35-mg dose with 5 mg being a low enough dose to produce minimal effects; 4) acute tolerance was evidenced with multiple doses of cocaine for most of the measures; and 5) considerable between- and within-subject variability was observed in the pattern of responses to cocaine. PMID- 8208772 TI - Evidence for serotonergic involvement in saccharin preference in a two-choice test in rehydrating rats. AB - Adult male rats were adapted to a 20-h water-deprivation schedule and trained to drink a 0.1% sodium saccharin and water in a two-choice test (30 min). Several direct acting serotonergic receptor agonists (putatively agonists at the 5-HT2C receptor), MK212, mCPP, and TFMPP, respectively, blocked the saccharin taste preference normally exhibited in this test. Water intake was unaffected. Taken with earlier evidence that these drugs reduce salt taste preference in rehydrating rats, it appears that they may inhibit taste preferences more generally, and that this effect may be closely related to their well-documented anorectic effect. At 3.0 mg/kg, d-fenfluramine almost completely blocked the saccharin taste preference, although l-fenfluramine (0.3 and 1.0 mg/kg) exhibited only hyperdipsic effects. 5-HT creatinine sulphate (0.3-3.0 mg/kg) also produced hyperdipsic effects, but showed no sign of blocking sweet taste preference. As a positive control, it was also shown that the opioid receptor antagonist, naloxone, reduced saccharin taste preference. PMID- 8208773 TI - Central and peripheral components of the inhibitory actions of 5-HTP on ethanol consumption in the rat. AB - When administered under a backward conditioning paradigm, 5-HTP administration resulted in a decrease in ethanol intake followed by a persistently decreased ethanol consumption. A central component to this inhibitory effect was suggested by the inability of xylamidine to significantly reduce the initial inhibitory effect of 5-HTP. The persistent rejection was prevented by xylamidine. Methysergide reduced the initial as well as the persistent effects of 5-HTP. In studies utilizing a forward conditioning paradigm, 5-HTP and lithium were each effective in developing CTAs to ethanol and saccharin. Only the ethanol-5-HTP pairing showed a persistent aversion. A peripheral component to the actions of 5 HTP was suggested by xylamidine blocking the CTAs induced by 5-HTP. Xylamidine also prevented the persistent ethanol avoidance induced by 5-HTP, but was ineffective in antagonizing lithium-induced CTAs. These results suggest central as well as peripheral components associated with the inhibitory effects of 5-HTP on ethanol consumption. Central actions appear to mediate the initial inhibitory effects while peripheral actions appear to be associated with persistent avoidance of ethanol following 5-HTP treatment. PMID- 8208774 TI - Acute sensitization to opioid antagonists. AB - Acute morphine pretreatment sensitizes rats to the response rate-decreasing effects of opioid antagonists naloxone and naltrexone. The effect appears to be mu-opioid receptor specific, as pretreatment with non-mu-selective opioid agonists results in less pronounced sensitization. In the present study, food deprived rats were trained to respond for food reinforcement on a FI 3-min schedule (9.5 min) with multiple trials. Doses of opioid antagonists were administered cumulatively before each trial of a session following 4-h pretreatment with either vehicle or morphine (3.0 mg/kg). Morphine pretreatment sensitized rats to naltrexone, lowering its ED50 from 20 to 0.03 mg/kg. It also sensitized rats to naloxone and to diprenorphine, another pure antagonist. Morphine-induced sensitization was stereoselective among the optical isomers of the benzomorphans, cyclazocine, pentazocine, and N-allylnormetzocine. In addition, acute morphine pretreatment resulted in sensitization to the mixed agonist/antagonist nalorphine, but not to buprenorphine or nalbuphine. The results extend previous findings concerning the importance of the mu-opioid receptor in the development of sensitization to opioid antagonists. PMID- 8208775 TI - Influence of age on the development of rapid tolerance to ethanol. AB - Fischer-344 rats of three different ages (4, 13, and 25 months) were tested to determine the extent and duration of rapid tolerance to ethanol-induced hypothermia and hypnosis. There were no significant differences among groups with regard to maximal ethanol hypothermia (3.0-3.5 g/kg ethanol), nor did any of the groups display a significant change (rapid tolerance) in the maximal hypothermic response when tested with a second identical challenge 48 h later. Rapid tolerance to ethanol hypnosis was observed across groups at 48 h, utilizing two different dosing schemes. No tolerance was observed if 14 days were allowed to elapse between the initial and the test challenge. Young rats were observed to develop a greater degree of rapid tolerance than did middle-aged or old rats, using hypnosis as a measure. PMID- 8208776 TI - Monoamine systems in the discriminative effects of spiradoline, a kappa-opioid agonist. AB - The results of studies on mice indicate that the antinociceptive effects of kappa opioid agonists are due, in part, to activation of the 5-HT2 type of serotonin receptor. One objective of this study was to determine if the discriminative effects of spiradoline, a kappa-opioid agonist, are mediated by 5-HT2 receptors in rats also. A second objective was to confirm findings that dopamine receptor antagonists produce spiradoline-like discriminative effects (Ohno et al., 1992). Rats were trained to discriminate between spiradoline (3.0 mg/kg) and saline in a discrete-trial avoidance/escape procedure. In subsequent tests of stimulus generalization, the discriminative effects of spiradoline were not mimicked by fenfluramine (0.3-10 mg/kg) or fluoxetine (1.0-10 mg/kg), drugs that enhance serotonergically mediated neurotransmission, nor were they blocked by the 5-HT2 antagonists pirenperone (0.01-1.0 mg/kg) and ketanserin (0.1-10 mg/kg), or potentiated by fluoxetine pretreatment. Neither the dopamine receptor antagonists haloperidol (0.01-0.3 mg/kg) and sulpiride (3.0-100 mg/kg) nor the agonists apomorphine (0.03-0.3 mg/kg) and d-amphetamine (0.1-3.0 mg/kg) engendered spiradoline-like discriminative effects. These results demonstrate further the pharmacological specificity of the discriminative effects of spiradoline, but provide no evidence for mediation by serotonergic or dopaminergic systems. PMID- 8208777 TI - The effects of haloperidol and clozapine on PCP- and amphetamine-induced suppression of social behavior in the rat. AB - Previous work has shown that phencyclidine (PCP) and amphetamine decrease social behavior in rats. The purpose of the present study was to determine the effects of the dopamine antagonists clozapine and haloperidol on PCP- and amphetamine induced changes in rat social behavior. An intruder paradigm was used, in which rats were injected with drug and placed into a stable home colony of three other rats. Social behaviors were recorded for 30 min. Both amphetamine (4.0 mg/kg) and PCP (4.0 mg/kg) substantially reduced social behavior. Haloperidol and clozapine did not produce a general reversal of the effects of amphetamine or PCP on the total number of social behaviors. Nevertheless, 0.025 mg/kg haloperidol did reverse the effects of PCP and amphetamine on some of the specific social behaviors observed (side threats, mounting, crawling under). Clozapine had no effect on reversing the actions of amphetamine on social behavior, but 2.0 mg/kg clozapine did reverse the effect of PCP on side threats and mounting. These results indicate that DA antagonists do not restore normal social behavior in animals treated with PCP or amphetamine, but can reverse some of the effects of PCP or amphetamine on specific social behaviors. PMID- 8208778 TI - Intracerebroventricular but not intraperitoneal administration of aluminum attenuates vasopressin-enhanced retrieval of a passive avoidance task in rats. AB - We studied the influence of single intracerebroventricular (ICV) and intraperitoneal (IP) injections of the neurotoxin aluminum on the retrieval of a passive avoidance task in rats and on the vasopressin-evoked improvement of the recall of the task. It was found that ICV administration of the metal alone strongly decreases the retention time of a passive avoidance task, whereas IP application of aluminum prolongs it. Vasopressin given ICV and IP leads to an enhancement of retrieval (prolongation of the retention time). Vasopressin in combination with aluminum does not improve the recall of the task when both substances are given ICV. Intraperitoneal injection of the neuropeptide together with the metal improves the recall of the task. Our data point to the crucial importance of the route of application of aluminum for behavioral studies. PMID- 8208779 TI - Interactions between 5-hydroxytryptamine (5-HT) and testosterone in the control of sexual and nonsexual behaviour in male and female rats. AB - Two 5-hydroxytryptamine2 (5-HT2) agents, ritanserin and 1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane HCl (DOI) (both at 0.25 mg/kg IP), were administered to castrated males bearing graded testosterone implants (empty, 2.5-, 5-, and 10 mm length) and to normal and neonatally androgenized ovariectomized females bearing 10-mm testosterone implants. The results indicate that testosterone stimulates male sexual behaviour and appears to have a dose-related anxiolytic effect, but no effect on other nonsexual activities. 5-HT and testosterone had opposite effects on male sexual behavior, with ritanserin (5-HT antagonist) enhancing activity in both sexes and DOI (5-HT agonist) inhibiting behaviour in males, the latter being testosterone-dependent. Independent of testosterone, ritanserin reduced locomotion and exploration and increased anxiety in males, while DOI increased locomotion and exploration in both sexes. Ritanserin had a gender-specific effect on anxiety which was independent of testosterone, since in castrated males it was anxiogenic whether they bore testosterone implants or not, while in females it was anxiolytic whether the female were neonatally androgenized (250 micrograms/pup testosterone proprionate [TP] on day 1) or not. These results show that 5-HT and testosterone have opposite effects on male sexual behaviour and these may be interrelated. In adulthood, their effects on nonsexual activities are not inversely related and are independent of each other in contrast to the relationship seen in the neonatal period. PMID- 8208780 TI - Phencyclidine-induced behavioral sensitization. AB - Chronic administration of a psychomotor stimulant has been shown to produce progressively enhanced effects, a phenomenon called "reverse tolerance" or sensitization. The present study reexamined the effects of the daily injection of phencyclidine on locomotor activity and stereotypy in rats, and investigated whether drug-environment conditioning was necessary for the development of behavioral sensitization and whether (5R,10S)-(+)-5-methyl-10,11-dihydro-5H dibenzo[a,b]cyclohepten-5,1 0-imine hydrogen maleate (MK-801, dizocilpine) blocked behavioral sensitization to phencyclidine. Female Sprague-Dawley rats were used. Locomotor activity and stereotypy were measured automatically with the Digiscan system. The results confirmed an earlier finding that four daily injections of phencyclidine induced sensitization to both locomotor activity and stereotypy. The development of behavioral sensitization did not require drug environment conditioning. Moreover, MK-801 did not block behavioral sensitization to phencyclidine. The results of the present study suggest that the neuronal mechanisms underlying sensitization to phencyclidine are different from those underlying sensitization to amphetamine and cocaine. PMID- 8208781 TI - Inhibition of isotonic sodium chloride intake in the rat by selective tachykinin agonists. AB - The present study investigated the effect of the central injection of selective tachykinin (TK) agonists on the need-free intake of 0.9% NaCl in rats. Isotonic NaCl was offered for 60 min (between 1800 and 1900 h); water was offered for 4 h (between 1800 and 2200 h). The TK agonists were injected into the third ventricle just before access to fluids. The NK3-selective agonists [Asp5,6,MePhe8]substance P(5-11) and Succ[Asp6,MePhe8]substance P(6-11), as well as the NK1-selective agonist [Sar9, Met(O2)11]substance P, markedly reduced salt intake, the threshold dose for their effects being 5 ng/rat. The NK2-selective agonist GR64349 reduced salt intake only at 500 ng/rat. At the dose of 31.2 ng/rat, neither the NK1 nor the NK3 agonists inhibited water intake, when water was the only fluid offered (between 1800 and 2200 h), or modified food intake in food-deprived rats. The present study shows that a) TKs inhibit not only the need-induced salt intake, but also the need-free intake of isotonic saline, b) this effect is behaviorally selective, and c) the effect is apparently mediated by NK1 and NK3 receptors. The finding that TKs suppress salt intake in a large variety of experimental conditions supports the idea that the antinatriorexic effect of TKs is independent of the physiological and hormonal status of the animal. It is hypothesized that TKs might modify taste sensitivity or the hedonic evaluation of the salty taste. PMID- 8208782 TI - Differential changes in central monoaminergic metabolism during first and multiple sodium depletions in rats. AB - To investigate the role of central monoamines in the behavior of sodium appetite, serotonergic and dopaminergic metabolism in regions of the forebrain and dorsal hindbrain were measured in sodium-depleted rats. Male Sprague-Dawley rats were sodium depleted by injection of the diuretic-natriuretic drug, Lasix (furosemide, 10 mg), and maintained on a sodium-deficient diet overnight. Rats were tested at a first sodium depletion or after multiple sodium depletions. There were three test conditions: 1) mock depletion consisted of vehicle injection and overnight sodium-deficient diet; 2) sodium depletion alone consisted of Lasix injection and overnight sodium-deficient diet; and 3) intake of NaCl following sodium depletion consisted of 9-min access to 0.3 M NaCl after Lasix injection and overnight sodium-deficient diet. Dopamine (DA), DOPAC, HVA, 5-HT, and 5-HIAA were measured by HPLC in the olfactory tubercle, amygdala-pyriform lobe, n. accumbens, hypothalamus, caudate nucleus, and the dorsal hindbrain. Ingestion of 0.3 M NaCl for 9 min after the first sodium depletion increased 5-HIAA/5-HT ratio significantly in the n. accumbens and amygdala, and increased DOPAC/DA ratio in the n. accumbens and olfactory tubercle compared to the mock treatment. In contrast to the results after the first sodium depletion, rats that ingested 0.3 M NaCl after four or more sodium depletions had no changes in 5-HT and DA metabolism in the forebrain, but they did have a significantly larger 5-HIAA/5-HT ratio in the dorsal hindbrain than mock-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208783 TI - Single gene effect on alcohol preference in the Zucker rats. AB - Zucker obese (ZO), Zucker lean (ZL), and Sprague-Dawley (SD) naive rats of both sexes were used to study the role of the fa/fa gene on alcohol preference. During the first two weeks of this experiment (weeks 1-2) all rats received a 10% alcohol solution ad lib as the only source of liquid. Animals were then given free access to both water and alcohol for the following three weeks (weeks 3-5). Thereafter, rats were deprived of alcohol every other day for two weeks (weeks 6 7), then completely deprived of alcohol for one week (week 8). Finally, unlimited access to both water and alcohol solution was available for the last two weeks of the experiment (weeks 9-10). Results of this study show that when rats were offered both water and alcohol (weeks 3-5), ZL rats consumed significantly more alcohol (2.5-fold) than their littermates, the ZO rats and the SD rats. Similarly, during alternate days of alcohol deprivation (weeks 6-7), ZL rats consumed significantly more alcohol (threefold) than the ZO rats and the SD rats. After a week of alcohol deprivation (week 8), and during the final two weeks (weeks 9 and 10), ZL rats continued to consume significantly more alcohol (2.5 fold) than the ZO group or the SD group. ZL females consumed more alcohol per kg body weight than male ZL rats. Data obtained from this study suggest that in the Zucker rat a single gene can alter the animal alcohol preference. PMID- 8208784 TI - Voluntary oral morphine self-administration in rats: effect of haloperidol or ondansetron. AB - Rats were exposed to increasing concentrations of morphine hydrochloride (up to 0.4 mg/ml) in 5% w/v sucrose solution as their sole source of drinking water. Physical dependence was established as determined by the precipitation of withdrawal behaviour following administration of 1 mg/kg IP naloxone hydrochloride on day 23. The choice between either a 5% w/v sucrose solution or a 5% w/v sucrose solution containing 0.4 mg/ml morphine hydrochloride 4 days following withdrawal resulted in rats being categorized into two groups based on their respective consumption of the morphine-containing solution. The amount of morphine solution voluntarily consumed by approximately half the rats were sufficiently high as to lead to a relapse into physical dependence to morphine. The high preference for morphine shown by these rats could not be attributed to the taste of the morphine solution. Naive rats or rats exposed to a 5% w/v sucrose solution for 23 days failed to consume significant quantities of the morphine-containing solution when provided with a choice. The administration of either an IM slow-release formulation of 70.5 mg/kg haloperidol decanoate (= 50 mg/kg haloperidol) or 10 micrograms/kg IP ondansetron hydrochloride daily did not alter morphine ingestion in the high morphine-preferring rats. PMID- 8208785 TI - Electroconvulsive stimulations, learning, and protein changes in the rat brain. AB - Two groups of rats were subjected to 17 training sessions on an operant task demanding the sequential operation of two manipulanda, while two other groups were left with no training experience. Within both the trained and passive groups one was exposed to a series of 12 electroconvulsive stimulations. The series of training and stimulation sessions were concurrent but arranged in such a way that at least 24 h always separated training and stimulation. Upon completion of the behavioural part of the experiment the concentrations of the marker proteins neural cell adhesion molecule (NCAM), D3, synaptophysin, and S100 were estimated in the prefrontal and occipital parts of the cortex, the hippocampus, and in the total forebrain. The electroconvulsively stimulated animals demonstrated severe impairment of learning. The pattern of marker protein concentrations indicated that acquisition and/or performance of the task and exposure to electroconvulsive stimulation were both accompanied by similar patterns of synaptic changes: an increased concentration of small synaptic vesicles in both the prefrontal cortex and the total forebrain and an increased synaptic remodulation in the prefrontal cortex. PMID- 8208786 TI - HPLC-purified bovine satietin suppresses food intake and weight without causing conditioned taste aversion. AB - Satietin (SAT) is a putative satiety agent found in a variety of species including man and the rat. In the present study, satietin was extracted from bovine plasma (b-SAT) and further high-pressure liquid chromatography (HPLC) purified. Rats were given chronic third ventricle cannulas and patency was verified. In experiment 1, rats were divided into three groups and ICV infused with artificial cerebrospinal fluid (a-CSF) or b-SAT: group 1, a-CSF (n = 11); group 2, 20 micrograms/rat, b-SAT (n = 11); and group 3, 40 micrograms/rat, b-SAT (n = 9). Infusions were repeated thrice three days apart. Compared to a-CSF, the high b-SAT dose suppressed food intake for 24-h after each successive infusion. The low dose significantly decreased food intake only after the first infusion. Water intake was suppressed only after the first injection of the high dose. Body weight was decreased after the first and second infusions of both doses and following the third infusion of the high dose. In experiment 2, rats were trained to drink fluid for 1 h/day while food was ad lib. On day 1, both groups received no infusions and were given tap water. On day 2, the groups were ICV infused with a-CSF, but group 1 (n = 12) was given banana-flavored fluid (BFF) and group 2 (n = 12) almond-flavored fluid (AFF). On day 3, group 1 was again a-CSF-infused but given AFF, whereas group 2 received 40 micrograms/rat b-SAT and was given BFF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8208787 TI - Drug discrimination and receptor binding studies of N-isopropyl lysergamide derivatives. AB - Isopropyl (IPLA), N-methyl-N-isopropyl (MIPLA), N-ethyl-N-isopropyl (EIPLA), and N,N-diisopropyl (DIPLA) lysergamides were evaluated for lysergic acid diethylamide (LSD)-like activity. In rats trained to discriminate 0.08 mg/kg LSD tartrate from saline, each of the subject compounds completely substituted, with an ED50 two to three times larger than that of LSD except for DIPLA, which had an ED50 about eightfold greater. Similarly, all the compounds displaced [125I](R)-1 (2,5-dimethoxy-4-iodophenyl)-2-aminopropane ([125I]DOI) from rat cortical homogenates and displaced [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH DPAT) from rat hippocampal homogenates with KI values similar to those of LSD, again with the exception of DIPLA, which had about nine- and fourfold lower affinities, respectively. Interestingly, all the compounds had four- to fivefold lower affinities than LSD in displacing [3H]ketanserin from 5-HT2 binding sites. Molecular modeling studies found that all the compounds had low energy conformations similar to LSD. No correlation between the activity of the compounds and the preferred conformation of the amide substituents was apparent. In summary, N-alkyl-N-isopropyl analogs of LSD retain LSD-like activity in drug discrimination and 5-HT1A and 5-HT2 agonist binding assays only until the N-alkyl substitution is as large as ethyl; LSD-like activity dramatically drops when the second alkyl substituent is N-isopropyl. PMID- 8208788 TI - Dihydropyridine-sensitive calcium channels and barbiturate tolerance and withdrawal. AB - We have shown previously that the dihydropyridine calcium channel antagonist nitrendipine, given chronically, prevents the development of ethanol tolerance and physical dependence. The present study examines the effects on barbiturate tolerance and physical dependence. Nitrendipine, given acutely during withdrawal, provided little protection against barbiturate withdrawal, as measured by convulsive behaviour on handling. When nitrendipine was given chronically concurrently with the barbiturate, a prolonged protection against the withdrawal syndrome was seen. Acute nitrendipine significantly increased the latency of seizures in response to the partial benzodiazepine inverse agonist FG7142 during barbiturate withdrawal, but there was no effect on the seizure incidence in response to bicuculline. Chronic treatment with nitrendipine did not alter the development of tolerance to the ataxic or general anaesthetic actions of barbiturates, but evidence was found of a possible interaction between nitrendipine and pentobarbitone, which may have been pharmacokinetic. The results suggest that neuronal calcium channels may be involved to some degree in the development of the changes responsible for barbiturate withdrawal, but to a less extent than found previously for ethanol dependence. PMID- 8208789 TI - Influence of flumazenil on the learning-enhancing effect of ambocarb in rats. AB - The effects of flumazenil (Ro 15-1788) and a new beta-carboline, ambocarb (AMB), on learning were investigated using the multichoice maze. The drugs, administered either alone or simultaneously, were injected once a day before training for eight days. AMB, administered alone, improved the performance and decreased the working errors, whilst flumazenil had no effect on performance during its sole administration but weakly prevented the learning-improving effect of AMB. More significantly, flumazenil antagonized the motor activity depressed by AMB. In the study ex vivo, flumazenil decreased and AMB increased the apparent affinity of [3H]flunitrazepam to the central benzodiazepine receptors. Flumazenil reversed the action of AMB on the central benzodiazepine receptors, but failed to reduce significantly the modulative effects of AMB on [3H]muscimol and [35S]t butylbicyclophosphorothionate ([35S]TBPS) binding. These data indicate that flumazenil, due to its action on the central benzodiazepine receptors, more effectively reverses the inhibition of motor activity than the performance improving effect of AMB. PMID- 8208790 TI - Relationship between occurrence of tremor/convulsion and level of beta-carbolines in the brain after administration of beta-carbolines into mice. AB - Fifteen beta-carboline derivatives, including those found in the South American hallucinogenic plant Banisteriopsis caapi, were injected IP and IVC into mice. Subsequent behavioral changes were observed and the levels of the compounds in brain tissue were determined. It was found that following IP administration, tremors and/or convulsions were induced by beta-carbolines having aliphatic alkyl groups, but not by those with carbonyl and oxo groups substituted at carbon-1 of the C ring. These effects were potentiated by the presence of a methoxy group at carbon-7 of the A ring, and their duration of actions were prolonged by 3,4 dihydro derivatives. When induced, tremors/convulsions correlated with levels of beta-carbolines in the brain. The smaller ED50 values of beta-carbolines that cause tremors/convulsions showed lower levels of beta-carbolines in brain tissue. PMID- 8208791 TI - FPL 14294: a novel CCK-8 agonist with potent intranasal anorectic activity in the rat. AB - Cholecystokinin octapeptide (CCK-8) induces satiety in many species including man. However, its therapeutic utility is restricted due to its short biological half-life and poor bioavailability. FPL 14294 [4-(sulfoxy) phenylacetyl(MePhe6)CCK-6] is a CCK analog with enhanced metabolic stability that was comparable to CCK-8 in potency to contract isolated gallbladder and in affinity at the CCK-A and CCK-B receptor. However, FPL 14294 was more than 200 times more potent than CCK-8 in inhibiting 3-h feeding in 21-h fasted rats. FPL 14294 also possessed intranasal anorectic activity at 5 micrograms/kg, while CCK 8 was inactive at doses up to 500 micrograms/kg. Anorectic activity was inhibited by pretreatment with a CCK-A antagonist (MK-329) but not by a CCK-B antagonist (L365,260). The anorectic effects of CCK-8 and FPL 14294 were the result of a direct effect on feeding and not caused indirectly by effects on water intake. These results indicate that FPL 14294 is a potent, intranasally active, anorectic agent whose enhanced in vivo potency over that of CCK-8 may reflect differences in stability, bioavailability, or receptor kinetics. PMID- 8208792 TI - Effects of caramiphen and phencyclidine alone and in combination on behavior in the rat. AB - Because dextromethorphan (DM) has been shown to inhibit the locomotor stimulant effects of phencyclidine (PCP), this study explored further the possible interaction between drugs acting on DM and PCP receptor sites. Caramiphen, an antitussive that binds with high affinity to the DM site, was injected (IP) alone (15-120 mg/kg) or at two doses (15 or 60 mg/kg) 15 min before a challenge dose of PCP (1.25-20 mg/kg). Caramiphen alone dose-dependently increased ataxia, increased stereotypy, and had no effect on locomotor activity. PCP alone dose dependently increased ataxia, stereotypy, and locomotor activity, the latter showing an inverted U-shaped function. At both pretreatment doses, caramiphen enhanced locomotor activity and stereotypy when combined with low PCP doses but decreased these behaviors at high PCP doses. Caramiphen produced a dose-dependent additive effect on ataxia when combined with all PCP doses. It was concluded that, although caramiphen, like DM, inhibited the locomotor stimulant effects of selected doses of PCP, that interaction appeared to be due to other behaviors (e.g., ataxia/stereotypy) elicited by caramiphen combined with high doses of PCP. This study underscored the importance of using full dose ranges of PCP when attempting to antagonize its behavioral effects with other drugs. PMID- 8208793 TI - Effect of pentobarbital and gaseous anesthetics on rats selectively bred for ethanol sensitivity. AB - Rats have been genetically selected to have a differential hypnotic response to an acute injection of ethanol. These high alcohol sensitive (HAS) and low alcohol sensitive (LAS) rats were used to investigate commonalities of the mechanism of action of several gaseous anesthetics, pentobarbital and ethanol. Similar studies have been carried out extensively with mouse lines also differentially sensitive to ethanol (short- and long-sleep mice). Like the mice, the rats are also differentially sensitive to the two gaseous anesthetics, enflurane and isoflurane. However, in contrast to results with these mice, we find that the HAS and LAS rats are differentially sensitive to halothane and pentobarbital in the same direction as their sensitivity to ethanol. In other studies, the rats also have been found to be differentially sensitive to phenobarbital as are SS and LS mice. These results show that, by the use of these anesthetics in combination with selectively bred rodent lines, many new opportunities for dissecting the molecular mechanisms of anesthetic agents present themselves. PMID- 8208794 TI - Quantification of the depressive effects of diazepam on the guinea pig righting reflex. AB - The effects of 5 mg/kg/day diazepam (IP for 21-39 days) on righting reflex latency (RRL) and neuronal activity in the medial vestibular nucleus (MVN) were investigated in guinea pigs. Diazepam treatment increased the RRL relative to vehicle-injected controls (p < 0.05, ANOVA); although the average RRL in the diazepam-treated animals did decrease over time, this decrease was not statistically significant and therefore evidence of tolerance was not obtained. MVN slices were removed from diazepam-treated animals and recordings were made from MVN neurons in vitro. The average resting activities for MVN neurons in slices from diazepam-treated animals and uninjected animals from a previous study were not significantly different. PMID- 8208795 TI - Comparison of the discriminative stimulus function of ethanol following intracranial and systemic administration: evidence of a central mechanism. AB - Rats were trained using a two-lever drug discrimination procedure to press one lever following systemic administration of ethanol (1.0 mg/kg, IP) and another lever following IP injections of saline. After determination of an ethanol generalization curve (0.25-1.25 g/kg, IP), rats were surgically implanted with bilateral stainless steel guide cannulae that terminated in the lateral ventricles. Following surgery, the generalization curve was redetermined and did not differ from presurgery values. Then, generalization to bilateral intracerebroventricular (ICV) injections of ethanol (600.0 and 900.0 mM, 1.0 microliter/side) were administered alone and in combination with IP injections of ethanol. The ICV ethanol injections produced partial generalization, but the combination of ICV ethanol (600.0 and 900.0 mM) with IP ethanol (0.25 and 0.50 g/kg) injections were two- to threefold more potent then IP injections alone. Response rates were unaffected by any dose of ethanol tested. These data suggest central mediation of ethanol's discriminative stimulus function due to: 1) increased potency of systemically administered ethanol by centrally administered ethanol, and 2) partial generalization between centrally and peripherally administered ethanol. PMID- 8208796 TI - Disruption of two-way active avoidance behavior produced by nimodipine. AB - Nimodipine, a voltage-sensitive calcium channel blocker, has been suggested to be a procognitive drug. In the studies reported herein, we found that low doses of IP-injected nimodipine (0.5 and 0.05 mg/kg) impaired two-way active avoidance behavior. The acquisition phase of the training was the same for drug-treated and control animals. However, the nimodipine-injected rats achieved a significantly lower level of performance. The no-shock tests revealed much faster extinction of the learned behavior in drug-treated vs. control animals. These results could be interpreted as indicating learning-disruptive effects of nimodipine. PMID- 8208797 TI - Prewatering and haloperidol have similar effects on rats' response rate and duration. AB - Haloperidol (0.1 mg/kg) and 5-min prewatering were given to 12 rats on three occasions each to determine effects on fixed ratio 15 (FR 15) responding for water. Compared to baseline, both treatments significantly reduced rate (prewatering slightly more) and both significantly increased duration. Though similar, drug and prewatering effects showed enough differences to suggest that there are both anhedonic and motoric deficit components to haloperidol's effects on rats' lever-pressing behavior for water. PMID- 8208798 TI - Handling and/or saline injections alter basal and morphine-evoked changes in dopamine metabolites in the striatum and nucleus accumbens of rats. AB - The effect of IP saline injections on basal dopamine (DA), homovanillic acid (HVA), and dihydroxyphenylacetic acid (DOPAC), and morphine-evoked levels of DA, DOPAC, and HVA in the striatum (STR) and nucleus accumbens (NAC) of female Sprague-Dawley rats was quantified, using in vivo microdialysis. In the STR, saline injections twice daily over 3 days, then once on day 4 (2x /day group), resulted in higher basal DOPAC and HVA levels compared to unhandled rats (naive group), or rats injected with saline once daily for 4 days (1x /day group). DOPAC and HVA were greater after IP injection of 30 mg/kg morphine in the saline 2x /day group compared to the saline 1x /day and naive groups. In the NAC, DOPAC was higher after injection of morphine in saline-pretreated rats, compared to naive rats. These results suggest that handling and/or IP saline injections affect basal and morphine-evoked changes in DA metabolites in the STR, and morphine evoked DOPAC in the NAC. PMID- 8208799 TI - Fetal nerve healing: an experimental study. AB - An experimental study was performed to assess fetal nerve repair and regeneration both qualitatively and quantitatively. The posterior tibial nerves in one hindlimb were transected in 16 midgestational fetal lambs and in their mothers. The nerves were then repaired with epineurial sutures and allowed to progress to 2, 4, 6, and 8 weeks postinjury. Qualitative assessment was performed through standard nerve histologic staining, including Luxol fast and toluidine blue for myelin and Bielschowsky stain for axons, and quantitative assessment through nerve conduction velocity studies and morphometry to determine mean myelinated fiber diameter, total fiber number, and density. A frequency histogram of the distribution of myelinated nerve fibers according to fiber diameter also was generated. In our model, the subsequent fetal nerve response to injury was characterized by earlier degeneration than in the adult counterparts. Repair and regeneration proceeded with dense collagenous scar formation in both groups. Electrophysiologic studies showed nerve impulse conduction across the repair site only at 6 and 8 weeks postinjury in both fetus and adult. Action potential amplitudes at 6 and 8 weeks were measured at 3 to 5 percent of control nerves in both nerve types. No electrophysiologic differences in the recovery of the injured fetal and adult nerves could be identified. Morphometry revealed that fetal nerve regeneration appeared to occur at a rate equivalent to that of the adult, although by 8 weeks the total percentage of remyelinated nerves appeared more complete in the fetus than in the adult (87 versus 59 percent), suggesting that fetal nerves may have a more favorable regenerative capacity than their adult counterparts. PMID- 8208800 TI - Development of a new documentation system for facial movements as a basis for the international registry for neuromuscular reconstruction in the face. AB - None of the paresis scoring systems used satisfies an adequate description of all the details necessary to document the degree of facial paresis before and after any treatment. We developed a new documentation system considering all details of the history of the patient and of the treatment that could have any influence on the functional result. The third part of this "international registry for neuromuscular reconstruction in the face" concerns paralysis assessment, including quantitative measurements of the resting and moving face, besides qualitative parameters. A map of standardized static and dynamic points in the face was designed, and three-dimensional measurements of the movements of these facial points were performed with a VICON system in 16 healthy individuals. On the basis of the results, three real static points and representative dynamic points were selected as well as relations of these points most representative for the different facial movements. For data collection, a simple instrument (Frey's faciometer) was developed. A preliminary report is given on the clinical application of this new instrument. PMID- 8208801 TI - Reinnervated lateral antebrachial cutaneous neurosome flaps in oral reconstruction: are we making sense? AB - Eight patients who underwent a partial glossectomy and associated floor of the mouth resection for squamous cell carcinoma were reconstructed with a sensate radial forearm flap in which the lateral antebrachial cutaneous nerve was anastomosed to the (divided) lingual nerve. The patients were compared prospectively with matched controls who received noninnervated forearm flaps for the same defect. A "blinded" therapist performed detailed sensory testing at least 6 months following surgery. In all modalities examined, the sensate proved superior to the nonsensate flap and not statistically different from the opposite side of the tongue. Two-point discrimination and pressure sensitivity were much greater in the innervated forearm flaps than in the forearms from which they came. The results are discussed with reference to the density of sensory receptors, the degree of cortical representation, and the subcortical anatomy of the neurosensory tracts. It appears that the density of sensory receptors is not directly related to the sensory potential in a given tissue transfer and that this potential is more related to the cortical fidelity of the recipient nerve. A historical matched cohort of 10 patients receiving pectoralis flaps for similar defects also was examined. Although the follow-up was longer, reinnervation was of a very low order--even worse than with noninnervated forearm flaps. This work supports the concept that sensory reinnervation should be attempted whenever possible following ablative oral surgery. This would include suture or grafting of major sensory nerves as well as the reinnervation of flaps. PMID- 8208802 TI - Method for preparing an exact-size model using helical volume scan computed tomography. AB - Helical volume scan computed tomography is a recently developed technology by means of which detailed data for most facial bone areas can be accumulated in a very short period, i.e., about 30 seconds, a much shorter time than required with conventional computed tomography. From a clinical standpoint, this is extremely important. In this report we discuss the principles of a method for preparing actual-size models by laser lithographic procedures based on data obtained by helical volume scan computed tomography. With these procedures, it is possible to obtain a good reproduction with high accuracy, on the order of 0.5 mm, not only of the outer morphologic structure of the cranial and maxillofacial bones but also of portions of the inner structure of cavities such as the cranium and paranasal sinuses. The difference between the original and model was under 3 percent, as confirmed by constructing a model of the dry skull with helical volume scan computed tomography. Therefore, production of exact-size models using helical volume scan computed tomography data represents an important technological development, breaking through previous limits imposed by conventional simulations prepared with three-dimensional images using CRT. With the combined use of laser lithographics and helical volume scan computed tomography, operative methods for craniomaxillofacial surgery should improve significantly in the near future. PMID- 8208803 TI - An analysis of extradural dead space after fronto-orbital surgery. AB - This study was undertaken to evaluate several concerns regarding the extradural space resulting from elective fronto-orbital advancement or frontal sinus cranialization techniques. The questions are (1) Do infants undergoing these techniques have the potential to obliterate this space at an accelerated rate, e.g., within 1 or 2 days? (2) Do adults have any potential to obliterate the space? (3) Do children obliterate the space like infants or like adults? (4) What is the specific time sequence for dead-space obliteration? Twenty patients ranging in age from 6 months to 35 years were studied before and after fronto orbital advancement. The patients were divided into three groups: (1) infants (up to 15 months), (2) children (up to 9 years), and (3) adults (9 years and beyond). Postoperative intracranial dead space was assessed by serial CT scans. Ten patients had CT scans more than 14 days after surgery. These data demonstrate that intracranial dead space in infants is obliterated in a delayed fashion. Children tend to obliterate intracranial dead space in a manner similar to that of infants. Adults are able to obliterate the space over a longer, but finite, period of time as compared with infants and children. Part of the mechanism responsible for obliteration of the postoperative space may be enlargement of the ventricular system. PMID- 8208804 TI - Forehead-brow rhytidoplasty: reassessing the goals. AB - Forehead-eyebrow rhytidoplasty traditionally has been advocated for senile brow ptosis. As the procedure became more widely accepted, it became a routine consideration in facial rejuvenation surgery. Indeed, over time, forehead-eyebrow rhytidoplasty also has withstood the initial criticism that was lodged against it of limited longevity, and it is realized that as with all other lifting procedures, it will gradually succumb to time, gravity, and the aging process. Moreover, refinements in techniques have added versatility to the procedure so that a variety of problems encountered in the upper face in addition to brow ptosis can be addressed. Consequently, an eclectic population with a range of deformities benefits from the procedure. Recently, though, it has seemed that the pendulum is swinging back, and that some surgeons are hesitating to incorporate forehead surgery because patients are voicing dissatisfaction with it. In order to assess the goals and indications for surgery, we reviewed a series of 350 patients who had a variety of aesthetic complaints in the upper face. Traditionally, patients' "other" indications for surgery, exclusive of brow ptosis, have been referred to as secondary (minor) indications. Now, with closer scrutiny, it appears that such problems, including forehead rhytids, frown muscle imbalance, upper eyelid aesthetics, lateral temporal laxity, and an abnormal expression, as a newly defined group, may actually be more frequent reasons than brow ptosis alone for performing a forehead-brow rhytidoplasty. As evaluated by the authors and supported by independent reviewers, low brow position alone should now account for less than half the forehead-brow surgery candidates. Furthermore, it is recognized that in considering the benefits achieved for patients with brow ptosis, often the results were due to "ancillary" surgical maneuvers routinely employed for the secondary indications. On balance, surgeons are advised to avoid adhering to traditional formulas for skin excision/brow elevation when operating on the brow; these can ultimately be the source of unsatisfactory outcomes. We believe that this philosophy will ultimately account for improved outcomes in forehead surgery. In addition, objective guidelines for the upper face have been reviewed and visual criteria defined which can be used in supplementing established brow spatial relationships for determining the ideal normal criteria for the upper third of the face. PMID- 8208805 TI - The superficial-plane rhytidectomy revisited. AB - Complex procedures for aesthetic facial rejuvenation, such as the deep-plane, extended SMAS, subperiosteal, and composite rhytidectomies, have received significant attention in the literature and at recent symposia. Young plastic surgeons striving to achieve excellent results may be intimidated by these procedures and find them difficult to perform. We suggest a renewed interest in the superficial plane approach for facial rejuvenation. On the basis of our experience with a synthesis of result-oriented technical modifications in 750 patients, we present a procedure to offer not only the beginning but also the more experienced surgeon a safe and satisfactory surgical alternative that will provide both predictable and lasting results while limiting risks and avoiding complications. PMID- 8208806 TI - One-stage repair of blepharophimosis: a new method. AB - Blepharophimosis is a congenital malformation involving the orbital region. It is associated with ptosis of the upper eyelids, epicanthal folds, telecanthus, and flattened and widened nasal bridge. We have surgically treated five cases of blepharophimosis by a procedure in which nasal bone graft, medial canthoplasty, and fascial suspension are performed in one stage. There is not any kind of operation for repair of the flattened and widened bridge of the nose in the literature. We have treated this anomaly using bone grafts. The follow-up period was 1 to 2 years, and good results have been obtained. A flattened and widened nasal bridge should be repaired by using bone grafts in addition to medial canthoplasty and fascial suspension in blepharophimosis. PMID- 8208807 TI - Bilateral breast reconstruction: conventional versus free TRAM. AB - Free TRAM flap transfer is now routinely offered to patients requiring breast reconstruction. This study compares results of conventional superior-pedicled TRAM flaps and free TRAM flaps in bilateral breast reconstructions. A total of 92 breasts were reconstructed in 46 patients. Eighteen patients had free TRAM flap reconstructions, and 28 patients were reconstructed with conventional TRAM flaps. Comparison of average operative blood loss and average operative time for the two techniques showed blood loss of 575 cc and an operative time of 9.6 hours for the free TRAM reconstructions and a blood loss of 313 cc and an operative time of 6.6 hours for the conventional TRAM reconstructions. For free TRAM flap reconstructions, both blood loss and operative time decreased significantly between the first and second group of nine patients: from 819 to 360 cc of blood loss and from 10.5 to 8.9 hours of operative time. Partial flap loss (skin and fat necrosis) and fat necrosis only occurred in 13 and 7 percent, respectively, of conventional TRAM flaps, but neither occurred in free TRAM flaps. However, early in the series, three free flaps were lost in two patients, requiring implant placement. Bilateral breast reconstruction using the free TRAM flap may offer a lower complication rate than the conventional TRAM flap by virtue of improved blood supply and less abdominal wall disruption. Surgeons, however, are forewarned that this procedure has a steep learning curve, and surgeons lacking microsurgical expertise may be better served by the conventional TRAM flap. PMID- 8208808 TI - Changing trends in postmastectomy breast reconstruction: a 13-year experience. AB - Over the past two decades, significant advances have been made in the treatment of breast cancer and reconstruction following mastectomy. This analysis represents a 13-year review (1979-1991) of 455 postmastectomy reconstructions involving 381 patients (age range 25 to 76 years, mean 51 years). Follow-up was 6 months to 13 years (mean 5 years). Timing of the reconstruction, reconstructive techniques used, incidence of complications, and final results were determined. Reconstructions were divided into three chronologic study groups: group I, 1979 1983; group II, 1984-1987; and group III, 1988-1991. A significant increase in the use of autogenous reconstruction was identified: 13 percent in group I to 37 percent in group III (p < 0.0002). Complication rates were not significantly different among the three groups (p > 0.02). Significant decreases in the use of implants alone and the latissimus dorsi flap with implant were identified, while tissue expansion and TRAM flap use increased significantly (p < 0.002). Also, a significant increase in immediate reconstruction from 6 percent in group I to 28 percent in group III occurred (p < 0.0002). There was no significant difference in complication rates between immediate and delayed reconstruction in any study group. Operative time averaged 2 hours less for nonautogenous techniques; however, autogenous reconstruction required significantly fewer operative revisions. The identified trends toward immediate reconstruction and use of autogenous tissue have been accomplished without an increase in complications. Despite a decrease in overall implant use, the textured silicone saline-filled expander/implant remains the most frequently used device for breast reconstruction, providing a safe and predictable method to accomplish both immediate and delayed postmastectomy reconstruction. PMID- 8208809 TI - Skin thickness in expanded human breast skin. AB - By means of an ultrasonic technique, skin thickness was measured in 13 women subjected to mammary reconstruction by tissue expansion. Measurements were performed the day before introduction of the expander, after the last inflation, the day before introduction of the permanent implant, and at 2 weeks and 6 months after this operation. Five patients had their expanders inflated every day (rapid expansion), and 8 patients, once a week (slow expansion). A decrease in skin thickness during the inflation period was recorded, and this decrease was permanent even 6 months after the second operation. After exchange of the expander for a permanent implant, there was a transient statistically significant increase in skin thickness. There was no statistical difference between the groups of rapid and slow expansion. PMID- 8208810 TI - Single-stage management of 74 consecutive sternal wound complications with pectoralis major myocutaneous advancement flaps. AB - The optimal management of sternal wound complications remains controversial. Since 1985, we have utilized a combination of immediate, aggressive debridement with simultaneous repair using bilateral pectoralis major myocutaneous advancement flaps, regardless of the degree of infection. As compared with the use of distant pedicled muscle flaps or pectoralis major turnover flaps, the management of complicated sternal wounds with immediate pectoralis major myocutaneous advancement flaps provides an effective yet simpler, quicker method of management with improved aesthetic results. In addition, basing the pectoralis major myocutaneous flaps on the thoracoacromial arteries eliminates the need for intact internal mammary arteries, valuable since the latter are increasingly used for coronary grafts. Seventy-four consecutive patients, 17 (23 percent) of whom were immunosuppressed heart transplant recipients, have been managed with this procedure. There were no intraoperative deaths. The 30-day perioperative mortality rate was 9 percent (7 of 74), with only 1 death related to persistent sepsis. The morbidity rate was 39 percent, with the most common complication being seroma managed by needle aspiration (18 of 74, 24 percent). The aesthetic and functional results have been uniformly excellent. PMID- 8208811 TI - Proximal lateral leg flap transfer utilizing major nutrient vessels to the soleus muscle. AB - A new skin flap based on the cutaneous branches of the major nutrient vessel to the soleus muscle was designed and executed. An anatomic study of the major nutrient artery to the lateral half of the soleus muscle was performed on 26 legs. An angiographic study was performed on 27 legs. The major nutrient artery to the lateral half of the soleus muscle was classified according to its origin: the tibioperoneal trunk (type 1), the bifurcation of the posterior tibial and peroneal arteries (type 2), the posterior tibial artery (type 3), and the peroneal artery (type 4). The outer diameter of the major nutrient artery to the lateral half of the soleus muscle, by direct measurement, was 1.87 mm (range 1.1 to 2.5 mm). This new flap was applied in nine patients. The recipient sites were the great toe, the hand, the jaw, the anterior leg, the popliteal fossa, and the thigh. The vascular pedicle ranged from 6.5 to 9.5 cm in length. Tissue was transferred as a free flap in eight patients and as an island flap in one patient. All the flaps survived completely. PMID- 8208812 TI - Implantation and expansion of split-thickness skin grafts: a new source of prefabricated pedicle flaps and grafts. AB - The objective of this study was to determine whether a split-thickness skin graft can be implanted deep to the skin and whether it can be expanded. We also wanted to find out whether this implanted and expanded split-thickness skin graft can be used as a new source of skin grafts and as a pedicle flap. A tissue expander mounted on a Dacron sheet backing was specially designed for this experiment. Six female Hanford minipigs weighing 20 to 25 kg were operated on in three stages. In stage one, a split-thickness skin graft 0.03 in thick was harvested from the back, placed dermal side out over the expander, and sutured to the Dacron backing. The expander with the overlying split-thickness skin graft was then implanted deep to the panniculus carnosus muscle. Daily expansion was started 2 weeks after implantation to obtain a total volume of 1300 to 2500 cc. In the second stage, performed 4 to 6 weeks after implantation, the skin over the expander was elevated superficial to the panniculus carnosus muscle as a ventrally based flap, and the panniculus carnosus muscle was next elevated as a dorsally based flap lined on its deep surface with the implanted/expanded skin. Full-thickness skin grafts obtained from this implanted/expanded skin and from normal skin were transplanted to two 3 x 3 cm skin defects. The panniculus carnosus muscle implanted/expanded skin flap was then turned 180 degrees and sutured to a dorsally created skin defect. In the third stage, 4 weeks later, we noted the quality, texture, and appearance and obtained punch biopsies from normal skin, normal skin graft, implanted/expanded skin graft, and panniculus carnosus muscle implanted/expanded flap for histopathologic examination. All skin grafts "took" well, survived implantation, and were expanded successfully. The initial surface area of implanted split-thickness skin graft showed a net increase of 8 to 193 percent (mean percentage net increase 90 percent). This implanted/expanded skin also was retransplanted successfully to a skin defect. In all six minipigs, a skin-lined panniculus carnosus muscle implanted/expanded skin flap was constructed and survived transfer to an adjacent skin defect. The smallest flap of panniculus carnosus muscle implanted/expanded skin measured 10 x 12 cm and the largest 12 x 28 cm (mean surface area 228 cm2). PMID- 8208813 TI - Full-load expansion technique and preliminary clinical application. AB - For accelerating the inflation process of soft-tissue expansion, a continuous inflation protocol regarding pain as the criterion of overinflation, the full load expansion technique, has been introduced. It is carried out by restricting persistently the pressure in the expander near the pain threshold in a state of dynamic equilibrium between the infusing rate and the skin expansion velocity with a simple and practical device. This inflation is neither at a uniform infusion rate nor at a constant filling pressure. Nineteen expanders in 13 patients were inflated following this protocol. Their inflations were fulfilled in 5 to 20 days, depending individually on their anatomic regions, total volumes of infusion, areas of the overlying skin, and patient susceptibilities. PMID- 8208814 TI - Thromboxane as a measure of cutaneous vascular damage following irradiation. AB - The present study was designed to evaluate the role of thromboxane in radiation induced cutaneous injury and to use the quantitation of cutaneous thromboxane B2 as an indicator of vascular alteration and tissue viability in canine skin. Ten adult intact male dogs underwent epithermal neutron irradiation with or without boron neutron capture. Skin biopsies were obtained from (1) within, (2) the edge of, and (3) outside the radiation field at 5, 8, 11, 14, 21, and 90 days after irradiation. Clinical changes at each sampling time were assigned a numerical score. One-half of each biopsy was assigned a numerical score based on histologic changes. Thromboxane B2 was measured from the second half by enzyme immunoabsorbent assay. Thromboxane B2 concentration paralleled the response of clinical and histologic score over time, indicating the value of thromboxane measurement for evaluation of skin changes secondary to irradiation. PMID- 8208815 TI - Clinical experience with the 3M microvascular coupling anastomotic device in 100 free-tissue transfers. AB - The microvascular surgical anastomosis remains one of the most technically sensitive aspects of free-tissue transfers. To facilitate these often time consuming, difficult anastomoses, various anastomotic coupling systems have been introduced. The 3M microvascular anastomotic coupling device, a polyethylene ring pin device, was found to be highly successful in numerous animal studies. It has been available for use in human subjects for the last 4 years, but clinical experience remains sparse. Our clinical experience with the 3M coupler is reported in 100 free-tissue transfers. The average anastomotic time was 4 minutes. Mean follow-up was 8.6 months, and flap survival was 100 percent. The overall success rate for 3M (MACD) coupler use in microvascular anastomoses is 98.4 percent (121 of 123). Nine abandoned anastomoses were converted to sutured anastomoses intraoperatively. The over-all failure rate for 3M coupler anastomoses is 1.6 percent (2 of 123). We conclude that the 3M device is best suited for minimally discrepant, soft, pliable venous microvascular anastomoses and is unsuitable for end-to-side anastomoses in clinical situations. When carefully and selectively employed by a trained microvascular surgeon, the 3M coupler can be a safe, fast, and reliable adjunct for free-tissue transfers. PMID- 8208816 TI - Global flap ischemia: a comparison of arterial versus venous etiology. AB - It has been suggested by clinical observations that acute venous thrombosis following free-flap surgery results in more severe tissue injury than postoperative arterial thrombosis. This current study, in the pig model, was designed (1) to determine the rate of survival and the percentage area of flap survival in both cutaneous and myocutaneous flaps following a secondary venous ischemic insult, (2) to compare this with findings following a secondary arterial ischemic insult, and (3) to determine the reliability of laser Doppler flowmetry and dermofluorometry index in the prediction of necrosis outcome following both venous and arterial ischemic insults. A total of 116 flaps were elevated in 29 pigs. Data analysis documented a decrease in the rate of flaps surviving venous ischemia as compared with arterial ischemia or control and of arterial ischemia as compared with control. In contrast to our previous work, a lower rate of buttock flaps survived a secondary ischemic insult (of either arterial or venous etiology) than did the cutaneous component of the myocutaneous flaps. As expected, as the length of ischemia increased, the rate of flaps surviving decreased, as did the percentage area of survival. Although laser Doppler performed slightly better than dermofluorometry index, as measured on immediate reperfusion following secondary venous ischemia, both were relatively poor predictors of eventual survival or necrosis. Under conditions of immediate reperfusion following secondary arterial ischemia, dermofluorometry index proved to be a superior predictor of ultimate necrosis as compared with laser Doppler flowmetry. PMID- 8208817 TI - Deep dissection rhytidectomy: a plea for caution. PMID- 8208818 TI - Justice and publicity: a question of responsibility. PMID- 8208819 TI - The fate of plastic surgery in the proposed health care reform: was Beethoven really necessary? PMID- 8208820 TI - On morality, ethics, and the American Board of Plastic Surgery. PMID- 8208821 TI - Pedicled greater omentum transferred to the spine in a case of postoperative infection. AB - An alternate surgical treatment was proposed in a case of vertebral postoperative chronic infection. The combination of an anterior omental flap with a posterior internal fixation plus bone grafting was successful, allowing the patient to walk 8 weeks after surgery. This relatively short recovery period compares favorably with the long months of confinement to bed usually required after an all-anterior approach with bone grafting only. PMID- 8208822 TI - Palmar ganglion producing diminished sensation in the distribution of the radial digital nerve of the thumb: a case not previously reported. AB - An unusual presentation of a ganglion pointing in the palm is presented. Treatment was rendered by surgical excision using an extensile incision. Studies that would have no effect on decisions regarding the need for or the method of surgery were avoided, thus minimizing unnecessary costs in the management of this patient. PMID- 8208824 TI - Computers and plastic surgery. PMID- 8208823 TI - David Prince, 1816-1890. PMID- 8208825 TI - The Clinton health care plan and its effect on specialists. PMID- 8208826 TI - The Clinton health care plan. PMID- 8208827 TI - A plea for reducing the number of positions for residency training in plastic surgery. PMID- 8208828 TI - Health care issues. PMID- 8208829 TI - Oncologic aspects of augmentation mammaplasty. PMID- 8208830 TI - Unusual late reactions to Zyderm I injections. PMID- 8208831 TI - Endoscopic augmentation mammaplasty. PMID- 8208832 TI - The stent for vaginal construction. PMID- 8208833 TI - Institute of Reconstructive Surgery, Peshawar, Pakistan. PMID- 8208834 TI - Management of large scalp defects with local pedicle flaps. PMID- 8208835 TI - Managing the ruptured silicone gel breast implant. PMID- 8208836 TI - Bioplasty MISTI Gold breast implants. PMID- 8208837 TI - Digital nerve grafts. PMID- 8208838 TI - Leakage of silicone gel through a cutaneous fistula. PMID- 8208839 TI - Rupture and aging of silicone gel breast implants. PMID- 8208841 TI - Vertical versus inverted-T reduction mammaplasty. PMID- 8208840 TI - Rupture and aging of silicone gel breast implants. PMID- 8208843 TI - The complaint window is open. PMID- 8208842 TI - Malar implant infections resulting from recurrent infections of adjacent dental pathology. PMID- 8208844 TI - Treating locally aggressive sinus disease. PMID- 8208845 TI - Oligosaccharides as signals and substrates in the plant cell wall. PMID- 8208846 TI - Uncoating of clathrin-coated vesicles by uncoating ATPase from developing peas. AB - A cytosolic ATPase (an enzyme that dissociates clathrin from clathrin-coated vesicles in the presence of ATP) was isolated from developing pea (Pisum sativum L.) cotyledons using chromatography on ATP-agarose. After chromatography on phenyl Sepharose, the fraction with uncoating activity was enriched in a doublet of 70-kD peptides. Using chromatofocusing, it was possible to produce fractions enriched in the upper component of the doublet of 70-kD peptides; these fractions still retained ATP-dependent uncoating activity. In western blot analysis, antibodies against a member of the 70-kD family of heat-shock proteins interacted with the upper component of the doublet of the 70-kD peptides from the phenyl Sepharose-purified fractions. On the basis of these data, it appears that the uncoating ATPase may be a member of the 70-kD family of heat-shock proteins. The uncoating activity removed clathrin from both pea and bovine brain clathrin coated vesicles. The uncoating ATPase from bovine brain also uncoated coated vesicles from peas. Pea clathrin-coated vesicles that were prepared by three different methods were uncoated to different extents by the plant uncoating ATPase. Different populations of clathrin-coated vesicles from the same preparation showed differential sensitivity to the uncoating ATPase. Limited proteolysis of the clathrin light chains in the protein coat abolished the susceptibility of the clathrin-coated vesicles to the uncoating ATPase. The properties of the uncoating ATPase isolated from developing pea cotyledons are similar to those of uncoating ATPases previously described from mammalian and yeast systems. It appears that despite dissimilarities in composition of the clathrin components of the vesicles from the respective sources, uncoating is achieved by a common mechanism. PMID- 8208847 TI - A gene that encodes a proline-rich nodulin with limited homology to PsENOD12 is expressed in the invasion zone of Rhizobium meliloti-induced alfalfa root nodules. AB - To define the early stages of the interaction between Rhizobium and host legumes, we have cloned and characterized three early nodulin-encoding sequences from an alfalfa (Medicago sativa L.) cDNA library by probing with a fragment of a cDNA clone for PsENOD12, an infection-related nodulin from pea (Pisum sativum L.). Although the coding regions of the three clones are 95 to 98% homologous to each other, they are only 43% homologous to the pea clone. However, the putative signal peptide encoded by the alfalfa cDNA clones is 100% homologous to the PsENDO12 signal peptide. The spatial and temporal expression patterns of PsENOD12 and the alfalfa clones were compared. In situ hybridization experiments detected RNA transcripts in the invasion zone of mature nitrogen-fixing nodules, the same site where PsENOD12 mRNAs are found. Transcripts were also found by in situ hybridization in cells of Rhizobium meliloti exoH mutant-induced nodules penetrated by infection threads, but northern analysis did not detect transcripts in inf- (infection thread minus) nodules elicited by R. meliloti exoB nodules or in pseudonodules elicited by treatment with the auxin transport inhibitor N-1 (naphthyl)phthalamic acid. In addition, the alfalfa gene represented by these cDNA clones exhibited a temporal expression pattern that differed from that of PsENOD12, which is transiently expressed. These data, plus information derived from Southern blot analysis, indicate that we have isolated cDNA clones for a novel early nodulin, which we have designated MsENOD10 (Medicago sativa Early Nodulin 10). PMID- 8208848 TI - The N-terminal cysteine-rich domain of tobacco class I chitinase is essential for chitin binding but not for catalytic or antifungal activity. AB - The vacuolar chitinases of class I possess an N-terminal cysteine-rich domain homologous to hevein and chitin-binding lectins such as wheat germ agglutinin and Urtica dioica lectin. To investigate the significance of this domain for the biochemical and functional characteristics of chitinase, chimeric genes encoding the basic chitinase A of tobacco (Nicotiana tabacum) with and without this domain were constructed and constitutively expressed in transgenic Nicotiana sylvestris. The chitinases were subsequently isolated and purified to homogeneity from the transgenic plants. Chromatography on colloidal chitin revealed that only the form with the N-terminal domain, and not the one without it, had chitin-binding properties, demonstrating directly that the domain is a chitin-binding domain (CBD). Under standard assay conditions with radioactive colloidal chitin, both forms of chitinase had approximately the same catalytic activity. However, kinetic analysis demonstrated that the enzyme without CBD had a considerably lower apparent affinity for its substrate. The pH and temperature optima of the two chitinases were similar, but the form with the CBD had an approximately 3 fold higher activation energy and retained a higher activity at low pH values. Both chitinases were capable of inhibiting growth of Trichoderma viride, although the form with the CBD was about three times more effective than the one without it. Thus, the CBD is not necessary for catalytic or antifungal activity of chitinase. PMID- 8208849 TI - Xyloglucan endotransglycosylase activity in pea internodes. Effects of applied gibberellic acid. AB - Xyloglucan endotransglycosylase (XET) activity extractable from internodes of tall and dwarf varieties of pea (Pisum sativum L.) was assayed radiochemically using tamarind seed xyloglucan as donor substrate and an oligosaccharidyl [3H]alditol as acceptor substrate. Internodes I and II showed little elongation during the period 15 to 21 d after sowing; XET activity remained relatively constant and was unaffected by exogenous gibberellic acid (GA3). A single application of GA3 to the dwarf genotype resulted in a small enhancement of elongation in internode III between d 17 and 21 and caused a small increase in XET activity in internode III. Repeated applications of GA3 caused internode V to elongate between d 20 and 26, to the same extent as in the tall variety, and concomitantly led to greatly elevated XET activity (expressed per unit fresh weight, per unit of extractable protein, and per internode). Thus, XET activity correlated with GA3-enhanced length in pea internodes; the possibility that this represents a causal relationship is discussed. PMID- 8208850 TI - Ripening-related polygalacturonase cDNA from avocado. PMID- 8208851 TI - A cDNA clone for flavanone 3-hydroxylase from Malus. PMID- 8208852 TI - A Cyanidium caldarium allophycocyanin beta subunit gene. PMID- 8208853 TI - Sequence of a (1-3,1-4)-beta-glucanase cDNA from oat. PMID- 8208855 TI - An Arabidopsis cDNA encoding a 33-kilodalton laminin receptor homolog. PMID- 8208854 TI - Cloning of a class III acidic chitinase from chickpea. PMID- 8208856 TI - Sequence of a novel abscisic acid- and drought-induced cDNA from wild tomato (Lycopersicon chilense). PMID- 8208858 TI - Effect of cutting on solute uptake by plasma membrane vesicles from sugar beet (Beta vulgaris L.) leaves. AB - The uptake of sucrose, 3-O-methylglucose (3-O-MeG), and valine were studied in discs and in purified plasma membrane vesicles (PMV) prepared from sugar beet (Beta vulgaris L.) exporting leaves. The uptake capacities of freshly excised leaf discs were compared with the uptake in discs that had been floated for 12 h on a simple medium (aging) and with discs excised from leaves that had been cut from the plant 12 h before the experiments (cutting). After cutting, sucrose uptake amounted to twice the uptake measured in fresh discs, whereas the uptake of 3-O-MeG and valine remained unaffected. In aged leaf discs, there was a general stimulation of uptake, which represented 400, 300, and 400% of the uptake measured in fresh discs for sucrose, 3-O-MeG, and valine, respectively. Sucrose uptake in fresh discs was sensitive to N-ethylmaleimide (NEM), to p chloromercuribenzenesulfonic acid (PCMBS), and to mersalyl acid (MA). Although cutting induced the appearance of a sucrose uptake system that is poorly sensitive to NEM but sensitive to PCMBS and MA, aging induced the development of an uptake system that is sensitive to NEM but poorly sensitive to PCMBS and MA. Autoradiographs of discs fed with [14C]sucrose show that cutting resulted in an increase of vein labeling with little effect in the mesophyll, whereas aging induced an increase of labeling located mainly in the mesophyll. The data show that cutting is sufficient to induce dramatic and selective changes in the uptake properties of leaf tissues and that the effects of cutting and aging on the uptake of organic solutes are clearly different. Parallel experiments were run with purified PMV prepared from fresh and cut leaves. The uptake of sugars and amino acids was studied after imposition of an artificial proton motive force (pmf). Comparison of the uptake properties of PMV and of leaf tissues indicate that the recovery of the sucrose uptake system in PMV is better than the recovery of the hexose and of the valine uptake systems. As observed with the leaf discs, cutting induced a 2-fold increase of the initial rate of sucrose uptake in PMV but did not affect the uptake of valine and 3-O-MeG. Cutting induced an increase of both Vmax and Km of the sucrose transport system in PMV. Measurements of the pmf imposed on the vesicles indicated that the increase of sucrose uptake induced by cutting was not due to a better integrity of the vesicles. Hexoses did not compete with sucrose for uptake in PMV from fresh and cut leaves, and maltose was a stronger inhibitor of sucrose uptake in PMV from cut leaves than in PMV from fresh leaves. The sensitivity of sucrose uptake to NEM, PCMBS, and MA in PMV from fresh and cut leaves paralleled that described above for the corresponding leaf discs. These data show that (a) the changes induced by cutting on sucrose uptake by leaf discs are due to membrane phenomena and not to the metabolism of sucrose; (b) the study of sucrose uptake with PMB gives a good account of the physiological situation; and (c) the specific effects induced by cutting on the sucrose uptake system are not lost during the preparation of the PMV. PMID- 8208857 TI - Expression of a 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from Camptotheca acuminata is differentially regulated by wounding and methyl jasmonate. AB - We have isolated a gene, hmg1, for 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) from Camptotheca acuminata, a Chinese tree that produces the anti-cancer monoterpenoid indole alkaloid camptothecin (CPT). HMGR supplies mevalonate for the synthesis of the terpenoid component of CPT as well as for the formation of many other primary and secondary metabolites. In Camptotheca, hmg1 transcripts were detected only in young seedlings and not in vegetative organs of older plants. Regulation of the hmg1 promoter was studied in transgenic tobacco using three translational fusions (-1678, -1107, -165) with the beta glucuronidase (GUS) reporter gene. Histochemical analysis of plants containing each of the three promoter fusions showed similar developmental and spatial expression patterns. In vegetative tissues, GUS staining was localized to the epidermis of young leaves and stems, particularly in glandular trichomes. Roots showed intense staining in the cortical tissues in the elongation zone and light staining in the cortex of mature roots. hmg1::GUS expression was also observed in sepals, petals, pistils, and stamens of developing flowers, with darkest staining in the ovary wall, ovules, stigmas, and pollen. Leaf discs from plants containing each of the translational fusions showed a 15- to 20-fold wound induction of hmg1::GUS expression over 72 h; however, this increase in GUS activity was completely suppressed by treatment with methyl jasmonate. Taken together, these data show that a 165-bp fragment of Camptotheca hmg1 promoter is sufficient to confer developmental regulation as well as wound induction and methyl jasmonate suppression of GUS expression in transgenic tobacco. PMID- 8208859 TI - The AVR9 race-specific elicitor of Cladosporium fulvum is processed by endogenous and plant proteases. AB - The avirulence gene avr9 of the fungal tomato pathogen Cladosporium fulvum encodes a race-specific peptide elicitor that induces a hypersensitive response in tomato plants carrying the complementary resistance gene Cf9. The avr9 gene is highly expressed when C. fulvum is growing in the plant and the elicitor accumulates in infected leaves as a 28-amino acid (aa) peptide. In C. fulvum grown in vitro, the peptide elicitor is not produced in detectable amounts. To produce significant amounts of the AVR9 elicitor in vitro, the coding and termination sequences of the avr9 gene were fused to the constitutive gpd promoter (glyceraldehyde 3-phosphate dehydrogenase) of Aspergillus nidulans. Transformants of C. fulvum were obtained that highly expressed the avr9 gene in vitro and produced active AVR9 peptide elicitors. These peptides were partially sequenced from the N terminus and appeared to consist of 32, 33, and 34 aa's, respectively, and are the precursors of the mature 28-aa AVR9 peptide. We demonstrated that plant factors process the 34-aa peptide into the mature 28-aa peptide. We present a model for the processing of AVR9 involving cleavage of a signal peptide during excretion and further maturation by fungal and plant proteases into the stable 28-aa peptide elicitor. PMID- 8208860 TI - Identification of methyl jasmonate and salicylic acid response elements from the nopaline synthase (nos) promoter. AB - Transgenic tobacco plants carrying a fusion between the nopaline synthase (nos) promoter and chloramphenicol acetyltransferase (CAT) reporter gene (cat) were studied for their inducibility by salicylic acid (SA) or methyl jasmonate (MJ) treatments. Either chemical significantly increased CAT activity to a level much higher than that achieved by wounding. Northern blot analysis showed a corresponding increase in mRNA levels. After 20 h of induction of flowering plants, the response to MJ treatment was weaker in old leaves compared with young leaves, whereas the SA response was stronger in old leaves. Kinetic experiments showed that the SA response was much faster than the MJ response, suggesting that the induction mechanism of the nos promoter by these chemicals may differ. Deletion analysis showed that both SA and MJ responses require the DNA sequence between -119 and -112 from the transcription initiation site. This region contains the hexamer sequence (TGACGT) that has been found to be an important regulatory element for several promoters. The MJ response was also reduced by deletions of the CAAT box region or the sequence between -112 and -101, whereas the SA response was not significantly affected by these deletions. This suggests that the nos upstream region containing the hexamer motif is essential for the SA or MJ response and that the CAAT box region and the sequence immediately downstream from the hexamer motif are required for maximum induction by MJ. PMID- 8208861 TI - [Brain imaging in schizophrenia -- especially by Computed Tomography]. AB - The evaluation of the contribution of structural and functional brain imaging to the contemporary understanding of schizophrenia is presented. The studies of schizophrenia using, especially, Computed Tomography (CT) and also Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET), are reviewed and their contribution to current theories of the pathogenesis of schizophrenia are discussed. This literature is reviewed for clinical, biochemical and environmental correlates of structural brain abnormalities in schizophrenia. The results are summarized and the critical questions raised by these studies are outlined. Future studies in this field are needed to yield current insight into the pathophysiology of schizophrenia. PMID- 8208862 TI - [The role of disturbances of the interhemispheric coordination in the pathogenesis of schizophrenia]. AB - In the opinion of some authors, the independent functioning of cerebral hemispheres may underlie schizophrenia. In the following study results of neuropsychological tests, similar to those obtained in split-brain patients, are presented. As a consequence of the early disturbance of interhemispheric coordination, anomalies of lateralisation of functions in schizophrenia are proven. Results of morphological examinations are presented, relating to structures responsible for interhemispheric transfer, including those in lower brain levels. Hypotheses indicating dysfunctions of those structures (especially of the pons) would explain many (not only dissociative) symptoms of schizophrenia. PMID- 8208863 TI - [Art therapy as a stimulation in the process of social adjustment of schizophrenia patients]. AB - The author presents the stimulation effect of arttherapy offered to schizophrenic patients, professional and amateurs painters--members of The Art Club of the Outpatients Clinic in Gdynia. The author shows the progress of arttherapy in the medical care not only for the psychiatric patients, but also for the chronically and terminally ill and for other people staying on long term basis in care houses, e.g. suffering from AIDS. The aim of the paper is to illustrate the positive changes in condition, familial and social status among schizophrenic patients--amateurs and professionals painters, members of "The Art Club" of the Outpatients Clinic in Gdynia. They were encouraged by therapists having the possibility of exposing their work in 9 public painting exhibition and by the collaboration with similar clubs in Poland and Belgium. One very interesting example of artist creator--whose work was exhibited at the Art Gallery in Brussels was discussed. The author observed an influence of this type of rehabilitation on club members in their private life, and stresses the very positive influence of art therapeutic stimulation on the family and social life of the chosen patients. PMID- 8208864 TI - [The influence of environment complexity and individual's reactivity on the genesis of schizophrenic delusions and on the differences in their content]. AB - The present paper tries to answer two questions: 1. Is there a connection between the occurrence of delusions in paranoid schizophrenics and the lack of them in healthy people, and the complexity of their environment and the level of their reactivity? 2. Is there a connection between the differentiation of the delusion's content, and the level of reactivity of the examined schizophrenics? Examined were 26 paranoid schizophrenics (13 with delusions of grandeur and 13 with delusions of persecution) and 26 healthy people. PMID- 8208865 TI - [Initial symptoms and risk factors in Alzheimer's dementia]. AB - The present paper summarizes recent data related to the risk factors for dementia of the Alzheimer type. More than 100 factors were reported in the literature but only two factors clearly implicated: age and family history of dementing illness. Among hypothesized environmental risk factors for dementia of the Alzheimer type, a previous head trauma was found significantly associated with the disease. Many other biological and psychosocial factors are discussed but the results are not consistent. PMID- 8208866 TI - [A reply to Dr. Bidzan's article "Relationship between the normal aging ad Alzheimer's dementia. Practical implications]. AB - In research on the etiology and pathogenesis of Alzheimer's disease much attention is devoted to the possible connections between this type of dementia and the ageing process of the brain alone, or the normal ageing accelerated or increased by certain adverse factors. There is cause to suppose, that normal ageing is only a certain ideal image. Indeed it is very difficult to meet an old person free from influences of adverse psychosocial and biological factors. There is no proof that these factors lead to primary degenerative dementia. To the contrary, there exist some indications that patients with Alzheimer's disease are physically healthier, than their undemented contemporaries. Epidemiological studies, neuropathological, neurochemical and genetics research, together with the clinical picture and the course of Alzheimer's disease, indicate that this is a different state from normal ageing. In research on the etiology of Alzheimer's disease it is important to establish not only risk factors, but also protective factors. Nevertheless due to the significance of Alzheimer's disease in Poland, in the nearest future, more attention will be devoted to vascular dementia. It is possible that the prevalence of vascular dementia is equal, if not greater than the prevalence of Alzheimer's disease. Because of the fact that the risk factors for vascular dementia are well known, it gives a possibility of prophylaxis and treatment of this type of dementia. PMID- 8208867 TI - [On the causes of homicide committed by women and the victim's character]. AB - The author discusses the importance of situational factors as victimological conditions in murders committed by women. The paper determines some objective properties of the situation, their links with motivation, and personality traits of the victim and the offender. PMID- 8208868 TI - [Court statements by psychiatrists and the information about the victim]. AB - The author examined 90 psychiatry court statements of individuals suspected of battering the women with whom they were cohabiting. The goal of the study was to assess to what extent psychiatry court experts were interested in the victim involved, and whether they considered the victim's possible influence on the offender's mental state at the time of the crime. The number and scope of the information about the victim as contained in the court statements have also been assessed. Moreover, the source of the victim data was scrutinised. It turned out that there were very few trace and random pieces of information concerning the victim. Only in two cases fact that the impact of the victim had an effect on the mental state of the offender was taken into consideration. The author suggests that experts should explore the possible influence of the victim on the mental state of the offender at least in cases of evident victim-offender interaction. PMID- 8208870 TI - Neurocognitive abilities for a clinically depressed sample versus a matched control group of normal individuals. AB - Depressed patients have been reported to show deficits in tasks that demand memory, planning/sequencing, speeded responding, and effortful responding. Many studies of depressed patients have used inadequate instrumentation or poor control groups. In this investigation, the cognitive performance of 44 patients diagnosed as clinically depressed was compared with the performance of a control group of normal individuals that closely matched the clinical group on the variables of age, gender, race or ethnic group, and educational attainment. The groups were compared on the tasks that compose the Kaufman Adolescent and Adult Intelligence Test (KAIT), which includes reliable and valid measures of most pertinent areas of purported deficit in depressed patients. Multivariate analyses of variance indicated that the depressed and control groups did not differ significantly on KAIT variables, but the depressed patients did differ significantly from the control group on the delayed versus immediate recall of verbal information. PMID- 8208869 TI - [Anxiety disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association: diagnostic and statistical manual of mental disorders (DMS-IV -- options book]. AB - In 1991 the American Psychiatric Association proposed a draft version of the IV edition of Diagnostic and Statistical Manual of Mental Disorders--the DSM IV Options Book. Authors of this version wanted to increase clarity of the criteria sets and to provide compatibility with the Tenth Edition of the International Classification of Diseases (ICD-10). The purpose of this Options Book is to propose some changes in wording, diagnostic divisions and to discuss various options concerning the placement of sections and disorders within the classification. The "Disorders of Infancy, Childhood or Adolescence" section was renamed "Disorders Usually First Evident in Infancy, Childhood or Adolescence" and moved to the front of the classification and also was expended to 11 groups of disorders. Several suggestions have been made about including new diagnostic groupings such as: Rett's Disorder, Eating Disorders and Voice Disorder. The Options Book introduces a superior category for Attention Deficit Disorders (with and without hyperactivity) and for Conduct Disorder/Oppositional Defiant Disorder. Several options are proposed regarding The Anxiety Disorders of Childhood or Adolescence. Since there is no evidence for distinction in this category according to the age criterion, one option would be to move these disorders into the adult anxiety section (similarly to the Mood Disorders and Schizophrenia). In the new version the title "Specific Developmental Disorders" is omitted. The suggestion is to include Phonological Disorder (Articulation Disorders) and Elective Mutism in the Speech and Language Disorders section. PMID- 8208871 TI - Early REM sleep: a compensatory change in depression? AB - To test for a possible mood-regulatory function of dreaming, the dream reports of 61 subjects undergoing divorce were scored for their dream-like quality (DLQ), and a difference score (DLQd) was computed between the content of rapid eye movement (REM) period 1 and the mean of the subsequent dreams of the night. Subjects with reduced latency to the first REM period had enhanced first dream DLQ scores in relation to the mean of later dreams (DLQd+ score). Those with DLQd+ had significantly higher scores on the Beck Depression Inventory (BDI). Depressed subjects with DLQd+ showed significantly lower mean BDI scores at followup assessment. Implications for a psychological function of dreaming are discussed. PMID- 8208872 TI - Influence of the cholinesterase inhibitor galanthamine hydrobromide on normal sleep. AB - Evidence from animal experiments has suggested that the triggering and maintenance of rapid eye movement (REM) sleep is mainly under the control of cholinergic neurons in the brain stem. Correspondingly, studies in humans have demonstrated that the application of cholinergic agonists or cholinesterase inhibitors provokes an earlier onset of REM sleep. The present study investigated the influence of galanthamine hydrobromide, a reversible cholinesterase inhibitor, on REM sleep regulation in 18 healthy volunteers. After an adaptation night, the subjects were given two doses of galanthamine (10 mg and 15 mg) or placebo at 10 p.m. in a randomized double-blind design. Both doses of galanthamine shortened REM latency (with statistical significance depending on the definition of REM latency used), increased REM density, and reduced slow wave sleep mainly in the first non-REM cycle. Higher doses of galanthamine (15 mg) seem to be accompanied by unwanted side effects that warrant the application of a peripheral antidote. These results are comparable to those for other cholinomimetics and stress the usefulness of galanthamine for pharmacological challenge studies in healthy subjects and depressed patients. PMID- 8208873 TI - Cholinergic REM induction test with arecoline in depressed children. AB - Children with major depressive disorder often fail to exhibit electroencephalographic (EEG) sleep abnormalities similar to those reported in depressed adults. It was hypothesized that a cholinergic rapid eye movement (REM) induction test would contribute to the identification of EEG sleep abnormalities in depressed children. To test this hypothesis, prepubertal children meeting research diagnostic criteria for major depressive disorder (n = 33) and carefully screened healthy control children (n = 15) were enrolled in a 4-day psychobiologic protocol that included 1 night with infusion of arecoline (0.5 mg) during the first non-REM sleep period. Although there had been no significant group differences in baseline sleep measures, results on the arecoline night revealed significantly shorter REM latency in the group of depressed children compared with the control children (mean +/- SD = 105 +/- 51 minutes vs. 140 +/- 46 minutes). The design of the protocol (with an interval break immediately preceding the arecoline night) prevented a direct estimation of arecoline effects within subjects; however, these data provide promising preliminary results regarding cholinergic REM induction tests in childhood depression. PMID- 8208874 TI - Lithium sustains the acute antidepressant effects of sleep deprivation: preliminary findings from a controlled study. AB - Early morning sleep deprivation (patient awake from 0200 to 2200 hours) produces a same-day antidepressant effect in approximately one-half of patients with major depression. Unfortunately, these antidepressant effects are short-lived and patients usually relapse to baseline depression levels within 48 hours. Recent work suggests, however, that the use of lithium with early morning sleep deprivation sustains this rapid antidepressant effect and makes it clinically useful. In a 30-day study, we compared the abilities of four different treatments (lithium plus early morning sleep deprivation, lithium plus a control sleep deprivation procedure, and desipramine with either of the two sleep manipulations) to induce a rapid (next-day) and sustained antidepressant response in 16 depressed patients. Lithium plus early morning sleep deprivation produced a quicker response than lithium with the control sleep deprivation, and the response was sustained for at least 30 days. In this design, however, lithium/early morning sleep deprivation was no faster than either of the two desipramine/sleep deprivation conditions in inducing remission. These results support the results of previous studies and suggest further investigation of this novel sleep/pharmacologic intervention is warranted. PMID- 8208875 TI - Nocturnal and circadian body temperatures of depressed outpatients during symptomatic and recovered states. AB - Forty-one recurrent unipolar depressed outpatients were studied at baseline (symptomatic period) and at recovery. Rectal temperatures were measured continuously between 1800h and 0600h on 2 successive nights at each time point. In those 24 patients who recovered after receiving interpersonal psychotherapy (IPT) alone ("psychotherapy responders") and who thus remained drug-free throughout, there was no difference in nocturnal body temperatures between baseline and recovery time points. Moreover, nocturnal temperature patterns appeared to be very similar to those of a healthy contrast group (n = 17). The contrast group was not matched for age and gender with the patient group, though, so the comparison was only suggestive. At baseline, those recovering after psychotherapy alone (n = 24) did not differ from those eventually failing to respond to IPT and requiring medications to achieve recovery ("medication responders") (n = 17). Medication responders did show some baseline versus recovery differences in nocturnal temperatures, but these may possibly have been a function of the medications used. At recovery, a subset of 19 psychotherapy responders and 13 medication responders underwent an "unmasking" experiment involving 36 hours of wakeful bedrest. In the resulting endogenous temperature rhythms, there was no evidence of any reliable differences between the psychotherapy responder and medication responder patient groups. Both groups showed rhythms that were very similar to those of a healthy contrast group (n = 17), although, again, the contrast group was not matched for age or gender with the patient group. In conclusion, in measures of body temperature, at least, there appeared to be little evidence of circadian dysfunction in this group of recurrent outpatient depressives. PMID- 8208876 TI - GP consultation as a factor in the low rate of mental health service use by Asians. AB - Patients attending five Health Centres in areas of NW London with a high Asian population were asked to complete a questionnaire screening for non-psychotic psychiatric illness and to state why they had come to see their doctor. The GPs were also asked to rate the purpose of the consultation for those patients who scored above the cut-off point on the questionnaire. The screening questionnaire revealed equivalent rates of non-psychotic psychiatric morbidity in the White and Asian samples and no differences in the way their symptoms were presented. The differences that did emerge showed that Asian patients scoring above the cut-off for psychiatric caseness were more likely to state that they were consulting their GP about a physical problem and GPs were more likely to identify psychiatric morbidity in White than Asian patients who exceeded the cut-off threshold. The results suggest the possibility of an interaction between the ways in which patients experience and communicate psychological distress, their ethnic origin, and their GP's mode of responding. PMID- 8208877 TI - The Dubai Community Psychiatric Survey: acculturation and the prevalence of psychiatric disorder. AB - Dubai, an Emirate in the Gulf region, has experienced spectacular social change as a result of the exploitation of its oil reserves. The Dubai Community Psychiatric Survey was designed to study the effects of this social change on the mental health of female nationals. In this paper, we approach the problem by quantifying social change in two main ways: the first focused on social change at the individual level as measured by the Socio-cultural Change Questionnaire (Bebbington et al. 1993). The second examined the effect of social change at the community level by identifying areas of residence at different levels of development. We hypothesized that attitudes and behaviours markedly at odds with traditional prescriptions would be associated with high rates of psychiatric morbidity. On the individual level, the association between psychiatric morbidity and the amount of social change reflected in the behaviours and views of the subjects was not significant. However, there was a significant association between morbidity and between social attitudes and behaviours. At the community level, in contrast, the relationship between psychiatric morbidity and social change was significant: there was more psychiatric morbidity in areas at the extremes of the social change continuum. The hypothesis put forward in this study must be modified accordingly. PMID- 8208878 TI - Symptom profiles of psychiatric disorders based on graded disease classes: an illustration using data from the WHO International Pilot Study of Schizophrenia. AB - The Grade of Membership (GoM) model is a classification procedure which allows a person to be a member of more than one diagnostic class. It simultaneously quantifies the degrees of membership in classes while generating the discrete symptom profiles or 'pure types' describing classes. The model was applied to the symptomatology, history, and follow-up of 1065 cases in the WHO International Pilot Study of Schizophrenia. The model produced an eight diagnostic class or 'pure type' solution, of which five were related to the diagnostic concepts of schizophrenia and paranoid disorder, two types were affective disorders, and one asymptomatic type. A subtype of paranoid schizophreniform disorder found primarily in developing countries was identified. There was a strong association between pure types and the original clinical and computer generated (CATEGO) diagnoses. A GoM based psychiatric classification might more clearly identify core disease processes than conventional classification models by filtering the confounding effects of individual heterogeneity from pure type definitions. PMID- 8208879 TI - A short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): development and cross-validation. AB - Data from four studies were used to assess the psychometric properties of the 26 IQCODE items. The items were assessed in terms of item-total correlations, test retest reliabilities, correlations with indicators of current cognitive functioning and correlations with indicators of premorbid cognitive functioning. These data were used to develop a 16-item short form. The short form was cross validated in a new sample using dementia/delirium diagnosis as the validity standard. It was found to perform as well as the long form. PMID- 8208880 TI - Post-traumatic stress disorder: supportive evidence from an eighteenth century natural disaster. AB - Post-traumatic stress disorder was first recognized as a diagnostic category embracing reactions in response to overwhelming environmental stress 'outside the range of usual human experience' in DSM-III (APA, 1980). Such abnormal stressors are by no means a product of the twentieth century but have featured, sporadically, in all societies from the earliest civilizations. Longitudinal investigations of traumatic stress have rarely gone further back than the nineteenth century, and have been concerned, almost exclusively, with adverse effects following railway accidents and military combat. The present study, utilizing a mid-eighteenth century medical source, presents an analysis of the impact of a natural disaster on members of a peasant family trapped in an avalanche in the Italian Alps in 1755. PMID- 8208881 TI - Memory impairment in schizophrenia--a comparison with that observed in the Alcoholic Korsakoff syndrome. AB - Until very recently, memory impairment was not considered to be a central feature of schizophrenia, except in chronic, deteriorated patients. In this study of a heterogeneous sample of 40 patients with DSM-III-R schizophrenia, episodic memory impairment was found to be prevalent, and in some cases, severe. The degree of memory impairment was not attributable to neuroleptic or anticholinergic medication, or to poor motivation or cooperation. These results, therefore, replicate those reported by McKenna et al. (1990) and Tamlyn et al. (1992), who suggested that the pattern of memory impairment in schizophrenia may conform in important respects to that of the classic amnesic syndrome. However, in a direct comparison of the schizophrenic sample with 18 patients suffering from the Alcoholic Korsakoff Syndrome (AKS), both quantitative and qualitative differences were found to exist between the two groups of patients. In particular, the level of long-term episodic memory impairment was found in the AKS sample to be far greater than that in the schizophrenic group. An interesting possible double dissociation emerged between the two groups; although demonstrating superior episodic memory functioning, the schizophrenic sample were found to perform significantly more poorly than the AKS sample on a test of semantic memory. PMID- 8208882 TI - Multiple reciprocal relationships between in vivo cellular immunity and hypothalamic-pituitary-adrenal axis in depression. AB - Major depression is reportedly characterized by increased activity of the hypothalamic-pituitary-adrenal (HPA) axis and by in vivo immune activation. The present study was carried out in order to investigate the relationships between HPA-axis activity and in vivo immune function in depression. Towards this end the following parameters were measured: 24 h urinary cortisol (UC) excretion; basal and post-dexamethasone (DST) plasma cortisol, beta-endorphin/beta-lipotropin (beta END/beta LPH) and dexamethasone concentrations; and leucocyte subsets (i.e. lymphocytes, neutrophils, monocytes, CD4+, CD4+CD45RA+, CD4+CD45RO+, CD8+, CD8+CD57+, CD8+CD57-, HLA-DR+, CD25+ T cells, HLA-DR+, CD19+, CD20+, and CD21+ B cells) both pre- and post-DST. Dexamethasone administration (1 mg orally) induced leucocytosis, lymphocytopaenia, monocytopaenia and neutrophilia. HPA-axis non suppressors exhibited a relative resistance to the enhancing (e.g. neutrophils) or depressant (e.g. lymphocytes, CD4+ T cells) effects of dexamethasone. There were significant correlations between UC excretion and the number of percentage of lymphocytes, monocytes, CD4+CD45RA+ and CD8+CD57- T cells (negatively) and neutrophils (positively). It is concluded that multiple and complex intertwined relationships between HPA-axis hyperactivity and systemic immune stimulation participate in the pathophysiology or pathogenesis of major depression. PMID- 8208883 TI - Incidence and relative risk of dementia in an urban elderly population: findings of a prospective field study. AB - To ascertain the frequency and distribution of new cases of dementing illness in the elderly population of Mannheim (population 308,000), a survey sample of community residents of > 65 years of age was re-examined after an interval of 7-8 years, and a sample of elderly persons in long-stay care after 5-6 years. The estimated annual incidence rate for all forms of dementia, after correction for ageing of the samples, was 15.4 per 1000 persons aged > 65, made up of dementia of Alzheimer type (8.9 per 1000), vascular dementia (4.4 per 1000) and other forms (2.1 per 1000). Apart from the expected association with age > 65 years, the most powerful predictors of onset of a dementing illness were residence in long-stay care and the presence of minor cognitive deficits at the initial examination, each of which was associated with a highly significant increase in risk. In addition, a number of socio-demographic characteristics (marital status, occupational history and quality of present living accommodation) was found to be predictive, though analysis of larger samples or pooled research data would be necessary to establish their importance in this respect. The findings suggest that identification of mild cognitive impairment on screening could prove helpful in assessing risk for dementia from two to three years before the condition becomes clinically apparent. PMID- 8208884 TI - Semantic memory is both impaired and anomalous in schizophrenia. AB - The integrity of semantic memory in schizophrenia was examined in a reaction time task requiring subjects to verify words as members or non-members of a conceptual category, where the words differed in their degree of semantic relationship to the category. Compared to matched normal controls, 28 schizophrenic patients were impaired on the task, showing slower responses in all conditions. In addition, their performance was anomalous in that they took longest to respond to items that were outside the category but semantically related to it, in contrast to the controls who took the longest to respond to ambiguous words at the borderline of the category. The pattern of 'yes' and 'no' responses of the patients was anomalous in a similar way. In both speed and accuracy of responding, the findings indicate that there is an outward shift of semantic category boundaries in schizophrenia. PMID- 8208885 TI - Lack of cognitive recovery following withdrawal from long-term benzodiazepine use. AB - Twenty-one patients with significant long-term therapeutic benzodiazepine (BZ) use, who remained abstinent at 6 months follow-up after successfully completing a standardized inpatient BZ withdrawal regime, and 21 normal controls matched for age and IQ but not for anxiety, were repeatedly tested on a simple battery of routine psychometric tests of cognitive function, pre- and post-withdrawal and at 6 months follow-up. The results demonstrated significant impairment in patients in verbal learning and memory, psychomotor, visuo-motor and visuo-conceptual abilities, compared with controls, at all three time points. Despite practice effects, no evidence of immediate recovery of cognitive function following BZ withdrawal was found. Modest recovery of certain deficits emerged at 6 months follow-up in the BZ group, but this remained significantly below the equivalent control performance. The implications of persisting cognitive deficits after withdrawal from long-term BZ use are discussed. PMID- 8208886 TI - Further reliability and validity studies of a procedure to assess the needs for care of the chronically mentally ill. AB - The Needs for Care Assessment Schedule (NFCAS; Brewin et al. 1987) is an itemized and systematic procedure that aims to evaluate the needs for care of long-term mentally ill patients. The present study pursues reliability and validity related issues with the NFCAS in a different cultural context applying the procedure to 98 severely mentally ill patients belonging to different patient groups: short term, long-term, in-patient and out-patient. Inter-rater reliability was found to be excellent. The results suggest that a clinician with little practical experience and adequate training may effectively use the procedure. The assessment of clinical relevance suggested that the procedure is both applicable and pertinent to all the patients in the study. Additional guidelines were developed for its use with long-term in-patients. PMID- 8208887 TI - Predictors for readmission risk in schizophrenia. AB - Readmission risk was assessed at the first and subsequent discharges in a total Danish national sample consisting of 8705 first admitted patients who had been discharged alive at least once with a diagnosis of schizophrenia. Predictors for readmission risk were identified using the Cox proportional hazards model. Following the first discharge, 19% of the surviving patients had not been readmitted after 10 years of follow-up. Readmission risk increased with the number of previous admissions. At the first discharge readmission risk decreased with increasing age and was significantly predicted by clinical subtype and gender. At later discharges (5th, 10th, and 15th) the effect of these variables gradually disappeared. At the 15th discharge readmissions were mainly predicted by the duration of the latest admission and discharge periods. Both the increase in readmission risk with the number of previous admissions and the evolving pattern of predictors for readmission risk are interpreted as supporting the existence of a smaller subpopulation among schizophrenic patients with frequent relapses. PMID- 8208888 TI - Do mental health surveys disturb? Further evidence. AB - In a community survey of 873 persons aged 70 years or over, focusing on dementia, cognitive decline, depression, and current life circumstances, we included an enquiry into the emotional impact of the interview. A large majority reported at the end of the interview that it had no adverse effect on their emotional state. About 4% reported that it made them distressed, 1% that it depressed them, and 2% that it had intruded on their privacy. By contrast, 52% said it had made them feel good about themselves. Distress seemed to be largely related to performing poorly on cognitive tests. There is no information on the duration of these effects in the period following the interview. It is recommended that respondents in community surveys, including the elderly, be informed that they can decline to answer any question, and that interviewers be trained in how to respond to the few who will be distressed by the experience. PMID- 8208889 TI - The dissociation of explicit and implicit memory in depressed patients. AB - Twenty-three in-patients fulfilling DSM-III-R criteria for major depressive disorder were submitted to a standard cued recall test, and to a word-stem completion test devised to assess the effect of the initial presentation without the explicit retrieval of the words being necessary. Results show that depressed patients are impaired on the cued recall task in comparison with controls matched for sex, age, and educational level. However, the two groups do not differ in the word-stem completion task. This dissociation between explicit and implicit expressions of memory disappeared when patients recovered, although they were still hospitalized and under psychotropic medication. These results are examined in the light of the distinction between effortful and automatic processes. PMID- 8208890 TI - A cautionary note regarding the interpretation of heritabilities. PMID- 8208891 TI - Can children with Gilles de la Tourette syndrome edit their intentions? AB - In this paper we describe a cognitive mechanism, the Intention Editor, which is triggered whenever there are several intentions competing in parallel with each other. This mechanism is hypothesized to be a subcomponent of a larger mechanism, the Supervisory Attentional System (SAS: Shallice, 1988) which serves inhibition in general. The Intention Editor interrupts one of several simultaneously activated intentions, preventing it from executing its action, utterance, or thought. This mechanism appears to develop during the first five to six years of life. We propose that an impairment in the development of this mechanism may account for the triad of symptoms in children with Gilles de la Tourette Syndrome (GTS): involuntary movements, involuntary utterances, and obsessive thoughts. This mechanism is tested with normal children aged 3-6 years old, and with children with GTS, in two experiments. In Experiment 1, subjects were required to make one hand movement while inhibiting making a (different) hand movement that the other hand was simultaneously making. In Experiment 2, they were asked to say one thing while inhibiting saying something else. On both tasks, normal 6-year olds were significantly better than normal 4-year-olds, but children with GTS performed worse than normal 6-year-olds, despite having a mean age of 12 years. These results constitute preliminary evidence for the theory that the Intention Editor is dysfunctional in GTS. PMID- 8208892 TI - The case for biology in the aetiology of anorexia nervosa. PMID- 8208893 TI - The subtyping of schizophrenia in men and women: a latent class analysis. AB - Latent class analysis on an epidemiologically based series of 447 first contact patients with a broad diagnosis of schizophrenia revealed evidence for two subtypes: a 'neurodevelopmental' type characterized by early onset, poor pre morbid social adjustment, restricted affect and a male:female ratio of 7:3; and a 'paranoid' type characterized by later onset, persecutory delusions and an almost equal sex ratio. A third 'schizoaffective' subtype, whose existence was less clear cut, was almost entirely confined to females and characterized by dysphoria and persecutory delusions, and had negligible familial risk of schizophrenia. The aetiological, biological and clinical significance of this typology remains to be tested. PMID- 8208894 TI - Clonidine infusion increases uptake of 99mTc-Exametazime in anterior cingulate cortex in Korsakoff's psychosis. AB - The effects upon regional brain function of infusing either saline or clonidine (1.5 microgram/kg) has been examined in 18 patients with alcoholic Korsakoff's psychosis using 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO or 99mTc Exametazime) and Single Photon Emission Tomography (SPET or SPECT). The hypothesis tested was that frontal lobe function would be increased by adrenoceptor stimulation. This was confirmed by an increase in the uptake of 99mTc-Exametazime into anterior cingulate regions of the frontal lobes. Patients were scanned before and after saline or clonidine infusion during performance of a verbal fluency task. There was a significantly increased performance of verbal fluency in patients given clonidine. This effect was variable and could not be unequivocably distinguished from increases in performance in the saline treated group. Nevertheless, the increase in neuropsychological performance was also correlated with increased function in left dorsolateral frontal cortex within the clonidine treated group. An exploratory examination of other brain areas suggested that relative increases in posterior cingulate cortex and changes in the symmetry of function within the thalamus may also be produced by acute infusion of clonidine in Korsakoff patients. The findings support the idea that adrenergic mechanisms may modulate cognitive performance by actions on attentional systems within the brain. These appear to be located primarily within limbic cortex. It is, of course, notable that this can occur in patients with profound and disabling amnesia. PMID- 8208895 TI - The use of psychiatric services before imprisonment: a survey and case register linkage of sentenced prisoners in Melbourne. AB - Information about contact with psychiatric services before imprisonment was obtained for a stratified random sample of sentenced prisoners, who were not receiving prison psychiatric care, in Melbourne's three metropolitan prisons. The sample of 158 men and 31 women was matched with the longitudinal person-linked records of state psychiatric service use in the Victorian Psychiatric Case Register (VPCR). Records of contact with the state services were found for 54 men (34%) and 19 women (61%), including records of in-patient treatment for 25 men (16%) and 15 women (48%). For 64% of individuals with a positive match, the case note diagnoses were substance use disorders only. Diagnoses of psychotic disorders were recorded for four prisoners, and mood disorders for another six. In addition, clinicians conducted standardized diagnostic interviews and enquired about treatment and personal history. A further 24 prisoners reported specialist psychiatric treatment outside the state treatment sector. This study links the findings from an interview survey of psychiatric morbidity in prisoners with the records available in the VPCR, and emphasizes a number of matters important to the public health. The high rates of previous treatment for substance abuse disorders, the apparent pool of prisoners with largely untreated major depression, and the service needs of those with chronic psychotic disorders are discussed. PMID- 8208896 TI - Comorbidity and co-transmission of alcoholism, anxiety and depression. AB - This paper applies data from a family study of depression to assess patterns of comorbidity and co-transmission of alcoholism, anxiety disorder, and major depression. We found that all three disorders were strongly transmissible; however, alcoholism demonstrated the greatest degree of familial aggregation. The pairwise associations among depression, anxiety and alcoholism indicated that the traits are co-transmitted in families, especially depression and anxiety. Individual associations between traits (or comorbidity) were entirely explained by transmitted (perhaps genetic) agents, because the correlations between traits due to random environment were not significant. These findings have important implications for treatment, psychiatric nosology, and aetiological investigations of these conditions. PMID- 8208898 TI - The Gospel Oak Study stage III: the incidence of dementia. AB - Of an original sample of 705 elderly (aged over 65) community residents 71% were rescreened after two years and four months using Short CARE. Thirty-one (6.7%) subjects were identified as possible new cases of dementia, implying a mean annual inception rate among the survivors of 26 per 1000. These were subjected to full clinical assessment, which yielded 10 cases of Alzheimer's disease (8 per 1000) and 5 multi-infarct dementia (4 per 1000). The remainder of the cases consisted of 6 with a dementia secondary to other causes, 1 case of mixed dementia and there was insufficient information to classify the remaining 3. Six were found not to be suffering from dementia. This yields an overall annual incidence rate for dementia among the survivors of 20 per 1000. PMID- 8208897 TI - University transition: major and minor life stressors, personality characteristics and mental health. AB - One hundred and two first-year students at an independent college in Taiwan participated in a questionnaire study. Measurements of stressors (major life events, minor daily hassles and perceived university stress), personality (locus of control, extraversion and neuroticism) and mental health (depression, anxiety and somatic symptoms) were taken. Using multivariate analyses, we found that: (1) life events predicted anxiety, while daily hassles predicted depression; (2) locus of control and extraversion correlated negatively, while neuroticism correlated positively with university stress; and (3) neuroticism had a main effect on symptom reportings across the board, while extraversion had a vulnerability effect on somatic symptoms. Relationships between life events and daily hassles, and the roles of personality in the stress process, are discussed. PMID- 8208899 TI - Psychological aspects of high and low blood pressure. PMID- 8208900 TI - Sex differences in lifetime depression rates: fact or artefact? AB - To isolate determinants of any female preponderance in depressive disorder, we earlier selected a sample of young adults, then similar in terms of several potential social determinants of depression and with equivalent rates of lifetime depression. We now report a 10-year review, which initially suggested a female preponderance in DIS-generated RDC and DSM-III lifetime depressive categories. The presence of sex differences in rates of lifetime depression was influenced by the definition of caseness used and the vantage point from which rates were determined. The longitudinal design and earlier corroborative witness reports established, however, clear evidence of instability in prevalence estimates, together with a sex effect on stability. Men were more likely to 'forget' episodes, while women were more likely to 'remember' episodes that had generally not previously reached 'case' criteria. When correction was made for such artefactual influences, a sex difference in lifetime depression rates was no longer evident. Such findings require review in general community samples, and suggest modifications to 'case' definition in epidemiological enquiries. PMID- 8208901 TI - New antiepileptic drugs. PMID- 8208902 TI - Familial nephropathic systemic amyloidosis caused by apolipoprotein AI variant Arg26. AB - A point mutation in the apolipoprotein AI (apoAI) gene causing autosomal dominant non-neuropathic systemic amyloidosis is described in a previously unreported Canadian family of British origin with five affected individuals in three generations. Amyloid deposits in the renal biopsy from the proband, a 31-year-old female presenting with hypertension and renal failure, stained immunospecifically with antiserum to apoAI. The plasma of all family members with amyloidosis contained both wild-type apoAI and a variant bearing one additional positive charge. Sequencing of the apoAI gene demonstrated that the proband was a heterozygote for a single base substitution in exon 3, changing codon 26 from GGC(Gly) to CGC(Arg). Concordance of the mutant allele with the presence of variant plasma apoAI and clinical features of amyloidosis was demonstrated. This is the third family in which this amyloidotic mutation has been described, but the distribution of amyloid deposits and their clinical effects are clearly determined by other genetic and/or environmental factors. PMID- 8208903 TI - Outcome of treatment in young adults with phenylketonuria detected by routine neonatal screening between 1964 and 1971. AB - Intellectual status at 18 years is reported in 192 patients with phenylketonuria born in the UK between 1964 and 1971, together with their school progress. Mean IQs expressed as standard deviation scores (IQ-SDS) were significantly below estimated population norms, and showed a small decrease from 14 to 18 years of age (mean IQ-SDS -1.06 +/- 1.3 at 14 years and -1.28 +/- 1.07 at 18 years, t = 5.7, p < 0.0001). At 18 years, 27% of subjects had IQs over 2 SDs below the estimated population mean. IQ-SDS at 18 years, although significantly related to average phenylalanine control both between birth and 14 years, and between 14 and 18 years, was not independently related to either variable after allowing for IQ SDS at 14 years. We conclude that general ability in young adults with early treated phenylketonuria, although reduced in comparison with their peers and closely related to phenylalanine control in early childhood, is not directly influenced by phenylalanine control in the four years preceding the 18th birthday. The apparent fall in IQ-SDS between 14 and 18 years may be due to methodological problems in the analysis of longitudinal IQ data without a control group, rather than providing evidence of intellectual decline. PMID- 8208904 TI - Classical versus non-renal Wegener's granulomatosis. AB - We investigated whether 'limited' or 'non-renal' Wegener's granulomatosis (WG) differs from classical or 'renal' WG. Renal WG is characterized by necrotizing granulomatosis of the upper and or lower respiratory tract, accompanied by systemic vasculitis and focal segmental necrotizing glomerulonephritis. This last feature is absent in non-renal WG. In a prospective follow-up study of all identified cases presenting to a single teaching hospital, we reviewed 22 patients with non-renal WG, and compared their presentation and outcome with that of 28 patients with renal WG. Clinical and laboratory assessment of disease activity, frequency of death, relapse and end-stage renal disease were assessed. The two groups differed in clinical presentation, laboratory features and outcome. The group with non-renal WG had less cutaneous and pulmonary disease; the haemoglobin, white cell count and platelet count tended to be normal. Residual mortality was confined to the renal group. However, the groups shared many features, particularly their requirement for immunosuppressive therapy, since WG causes major tissue destruction regardless of whether it is a localized or widespread process. At the immunopathological level, the two groups appear to be part of a single disease spectrum. Importantly, the non-renal WG group may change the pattern of their disease to involve the kidney. Long-term follow-up of such patients is therefore essential. PMID- 8208905 TI - Acute encephalopathy: diagnosis and outcome in patients at a regional neurological unit. AB - Sixty-five patients with a diagnosis of acute encephalitis or encephalopathy were discharged from a regional neurological unit over a 17-year period. Investigation during the acute illness, or subsequent clinical and laboratory observations, yielded a definite or probable diagnosis in 34 of these patients, including herpes simplex encephalitis (8 cases), encephalitis due to other identified viruses (7 cases), vascular disease (7 cases) and multiple sclerosis (4 cases). In these 34 patients, mortality relating to the presenting illness was 50% and a further 29% had significant long-term neurological morbidity. In the other 31 patients, no cause for the encephalopathy was identified, despite extensive investigation. These patients had an alteration in conscious state, often with recurrent seizures (45%), focal neurological signs (52%), pyrexia (65%), abnormal electroencephalogram (85%) and cerebrospinal fluid lymphocytosis (80%). During follow-up (6 months to 15 years) none had recurrent encephalopathy, and 65% eventually made a complete recovery, although delayed by seizures in 6% and psychiatric illness in 13%. The mortality in this group relating to the acute illness was 6%. Overall, nearly half the patients with a discharge diagnosis of acute encephalitis or encephalopathy had a good prognosis for recovery, following a monophasic illness of undetermined cause. PMID- 8208906 TI - Association of severe haemophilia A with osteoporosis: a densitometric and biochemical study. AB - Following a femoral neck fracture and vertebral compression fractures in two patients with severe haemophilia A, bone density and turnover were measured in 19 males with severe haemophilia A (all HIV negative, 18/19 hepatitis C antibody positive) and in 19 age/sex matched controls. Bone density at the lumbar spine (L2-4), measured by dual energy X-ray absorptiometry, was significantly lower in the haemophiliac patients (HPs) at (mean +/- SEM) 1.109 +/- 0.042 g/cm2 vs. 1.234 +/- 0.027 in controls; p = 0.018. Femoral neck density was also lower at 0.877 +/ 0.034 g/cm2 (HPs) vs. 1.067 +/- 0.032; p < 0.0005. No significant differences were evident between the groups for serum calcium, parathyroid hormone, luteinizing hormone, follicle-stimulating hormone or 1,25 dihydroxyvitamin D3, nor for fasting urinary hydroxyproline, pyridinoline or deoxypyridinoline excretion. Serum total alkaline phosphatases was elevated in HPs at 200 +/- 10 U/l vs. 158 +/- 8; p = 0.004. Similarly, gamma-glutamyl transferase was elevated at 42 +/- 7 U/l (HPs) vs. 20 +/- 2; p = 0.007. Serum total testosterone and sex hormone-binding globulin (SHBG) were higher in HPs at 26 +/- 2.5 nmol/l vs. 17.4 +/- 1.6 (p = 0.009) and 56 +/- 6 nmol/l vs. 27 +/- 3 (p = 0.0005), respectively. Free androgen index, however, was lower in HPs at 44 +/- 5 vs 69 +/- 7; p = 0.008. These results suggest significant osteopenia associated with haemophilia A. This may be partly due to liver dysfunction in HPs, but other factors, e.g. relative immobilization, may also be relevant. PMID- 8208907 TI - Why do doctors find some patients difficult to help? AB - Almost all doctors encounter difficulties in managing some patients. Previous studies have examined the characteristics of such patients: we have additionally studied the reasons why hospital doctors find these patients 'difficult to help'. Three clinics (two medical and one surgical) were studied. The consultants rated 60 (22%) of 293 attenders s severely or extremely difficult to help. Difficulty was associated with greater patient distress (odds ratio 3.9; 95% CI 2.0-7.7), less patient satisfaction (2.6; 1.3-5.0) and chronic attendance (5.0; 1.4-17.3). An interview study of 40 'difficult' patients indicated that doctors considered psycho-social factors more important in difficult patients (3.2; 1.3-7.7). Objective differences between the doctor's and the patient's aims for care also occurred more frequently for difficult patients (2.8; 1.1-7.2). Three common types of difficulty were identified; medically unexplained symptoms; co-existing social problems; and severe untreatable illness. A review of the management aims for patients whom doctors find 'difficult to help', combined with improved access to psycho-social care, could improve both the quality and the cost-effectiveness of hospital out-patient services. PMID- 8208908 TI - Drug-DNA interactions: new discoveries and possibilities for cancer treatment. PMID- 8208909 TI - Treatment of aggressive idiopathic membranous glomerulonephritis. PMID- 8208910 TI - Osteoporosis: recent advances in pathogenesis and treatment. PMID- 8208911 TI - Polymorphisms of the angiotensin-converting-enzyme gene in subjects who die from coronary heart disease. AB - It has been shown that myocardial infarction survivors are more likely to carry an insertion/deletion polymorphism (I/D) of the angiotensin-converting-enzyme (ACE) gene than age-matched population controls. To test whether the association with coronary risk had been under-estimated, the frequency of the ACE I/D was studied in 213 fatal cases of definite and possible myocardial infarction which came to autopsy in the Belfast MONICA Project area. In comparison to controls from the same population, the autopsy cases had an increased frequency of the ACE D allele (p < 0.02). The overall odds ratios were 2.2 for DD vs. II, and 1.8 for ID vs II (test for trend p = 0.01). The findings bear out the hypothesis that the ACE I/D polymorphism is a risk factor for fatal myocardial infarction and sudden cardiac death. PMID- 8208912 TI - Elevation of the 90 kDa heat-shock protein in specific subsets of systemic lupus erythematosus. AB - We have previously shown that the 90 kDa heat-shock protein (hsp90) is notably elevated in lupus patients with active neuro-psychiatric (NP) and/or cardio respiratory (CR) disease. This elevation is dependent upon enhanced transcription of the hsp90 beta gene. Serial studies have shown that changes in hsp90 levels have a high level of sensitivity for changes in activity of NP, CR, haematological and renal SLE. We now present evidence that overexpression of hsp90 in lupus patients is associated with the presence of the anti-phospholipid syndrome, and with the absence of the HLA allo-/haplotypes most commonly found in this particular cohort of patients. We conclude that the upregulation of hsp90 expression in SLE has a genetic basis, and that this may be directly involved in pathogenesis in subsets of patients with this disease. PMID- 8208913 TI - Prednisolone and chlorambucil therapy for idiopathic membranous nephropathy with progressive renal failure. AB - Twenty-one patients with membranous nephropathy, heavy proteinuria and progressive renal failure were treated with alternating monthly cycles of corticosteroids and chlorambucil for six months. Four patients received repeat courses. After a median period of follow-up of 39 months, three patients had died, six were receiving renal replacement therapy or had serum creatinine > 500 mumol/l, and one had progressive renal failure. Eleven patients had either stable or improved renal function, as judged by serum creatinine concentration. Of these eleven, four patients were in partial remission (daily protein excretion 0.2-2.0 g), and two were in complete remission. There was a tendency for those who received intravenous methylprednisolone to have a more favourable outcome. There was a high incidence of side-effects, with significant complications related to drug therapy observed in > 50% of subjects. Although individual patients appeared to respond well, sometimes dramatically, these results are less encouraging than other reports. We would urge caution in the use of this form of therapy, particularly in older patients who may have occult neoplasms, impaired glucose intolerance or pre-existing cardiac disease. PMID- 8208914 TI - Analysis of HLA-class-II-encoded antigen-processing genes TAP1 and TAP2 in primary biliary cirrhosis. AB - The search for genes involved in the aetiology of primary biliary cirrhosis (PBC) has centred on the major histocompatibility complex (MHC) on chromosome 6. Genotyping studies have confirmed an association with HLA class II allele DR8. We investigated polymorphisms in two newly identified genes (TAP1 and TAP2) situated close to the DR locus and thought to encode membrane transporter molecules involved in endogenous antigen processing. Genomic DNA extracted from PBC patients was compared with local healthy controls. TAP1 was analysed by amplification refractory mutation system (ARMS) PCR, and two alleles (A and B) were identified. In 126 PBC patients and 116 controls, allele frequencies were (A:B) 81:19% and 79:21%, respectively (NS). TAP2 analysis was by PCR followed by Bfal restriction digest, and again two alleles (A and B) were identified. Their frequencies in 109 PBC patients and 96 controls were (A:B) 76:24% and 73:27%, respectively (NS). No TAP1-TAP2 haplotype was associated with PBC. TAP allele frequencies were estimated within the DR8 subgroups (22 PBC, 14 controls). B allele frequency for TAP1 was increased in both DR8-positive PBC patients and controls compared with DR8-negative patients and controls (41% vs. 14% in PBC; 43% vs. 18% in controls), but no disease association was found. However, the increased frequency of TAP1B in DR8-positive subjects (42% DR8-positive vs. 16% DR8-negative, p < 0.001) indicates linkage disequilibrium between these two loci. PMID- 8208915 TI - DDD vs. VVI pacing in patients aged over 75 years with complete heart block: a double-blind crossover comparison. AB - We studied 16 patients aged 77-88 years to determine whether elderly patients gain significant benefit from dual-chamber (DDD) compared with single-chamber ventricular demand (VVI) pacing. The study was designed as a double-blind randomized two-period crossover study--each pacing mode was maintained for 7 days. End points included: (i) overall symptoms scores; (ii) exercise tests related to daily activities; and (iii) perceived level of difficulty (Borg score). The mean symptom score in DDD mode was 7.07 (6.38) vs. 12.27 (7.29) in VVI mode (p < 0.006). Dizziness, breathlessness and fatigue were the most noticed symptoms during VVI pacing. One patient dropped out from follow-up and three patients requested early reprogramming, all from VVI mode. Overall, no patient preferred VVI mode, 11 preferred DDD mode and four expressed no preference. There were significant improvements in all objective test performances in DDD mode. Mean (SD) total Borg scores in DDD mode and VVI mode were 36.57 (5.85) and 41.93 (6.49), respectively (p < 0.002). Ventricular demand pacing in elderly patients with complete heart block is associated with higher symptom scores, reduced exercise ability and greater perceived exercise difficulty compared with dual chamber pacing. PMID- 8208916 TI - New diagnoses for old diseases: dangers and distractions. PMID- 8208917 TI - Burnet and Nossal: the impact on immunology of the Walter and Eliza Hall Institute. PMID- 8208918 TI - Screening for early ovarian cancer. AB - There are 20,000 new cases of ovarian cancer per year and over 12,000 deaths in the United States. Seventy percent of women with ovarian cancer have advanced disease at diagnosis, and 5-year survival is less than 30%. Earlier diagnosis is essential to improve prognosis. Risk factors include age, race, ovulation, and family history. New techniques for possible earlier diagnosis include endovaginal color flow ultrasound (US) and measurement of a serum tumor marker, CA 125. CA 125 is only 25% sensitive for early disease and is nonspecific: In premenopausal women, more than 90% of findings are false-positive. Endovaginal color flow US provides superb morphologic detail of malignancy such as mural nodules and solid vascularized components. Low impedance flow has been reported in many cancers but may also be seen in benign masses and in luteal flow. There are technical and economic impediments to earlier diagnosis of ovarian cancer, and more sensitive and specific tumor markers may be required. Current techniques may show only acceptable cost-effectiveness in women at elevated risk by virtue of a family history of the disease. PMID- 8208919 TI - Glomus tumors of the skull base: combined use of MR angiography and spin-echo imaging. AB - PURPOSE: To evaluate the use of magnetic resonance (MR) angiography in the diagnosis of glomus tumors of the skull base. MATERIALS AND METHODS: In 40 patients with pulsatile tinnitus, spin-echo (SE) images, single sections, and maximum intensity projections from gradient-echo sequences, including arterial MR angiography and MR venography, were evaluated for tumor detection. Interpretations by two independent observers were correlated with findings from histologic examination, digital subtraction angiography, computed tomography, and clinical follow-up. RESULTS: Glomus tumors were detected near the tympanic plexus (n = 8) and close to the superior (n = 8) and inferior (n = 1) ganglia of the vagus nerve. Sixteen of 18 proved tumors were detected with SE images alone. Although four high-lying jugular bulbs were misinterpreted as tumor due to similar signal intensity, combined evaluation allowed differentiation between tumor and sinusal blood flow in all cases. CONCLUSION: The authors recommend combined SE imaging and MR angiography for ruling out tumor in patients with pulsatile tinnitus. PMID- 8208920 TI - Economic and cost-effectiveness investigations of radiologic practices. AB - Economic evaluations provide scientific data regarding the cost implications of radiologic practices and, most important, which strategies for patient care yield the best outcomes for the least cost. Although this article is meant to enrich understanding of cost-effectiveness studies, it cannot be regarded as a complete training program for undertaking such investigations. Just as training in clinical science is important for radiology research, training in the economics of health and medical care is important for performing economic investigations. Therefore, radiologists' work in this area is likely to be enhanced by involving an individual with appropriate economics training on the research team when conducting an economic investigation. Clinical radiologists and investigators in radiologic sciences should be capable of understanding and evaluating the design, performance, and interpretation of results of economic investigations, since radiology practice is likely to be influenced by the findings from such research. The principles described in this article are fundamental to generation of sound information that can guide radiologists' practice in an environment increasingly threatened by resource constraints (37). PMID- 8208921 TI - Intraoperative US of the pituitary gland. Work in progress. AB - PURPOSE: To evaluate the use of ultrasound (US) of the pituitary gland during transsphenoidal surgery as a means of detecting microadenomas in patients with Cushing disease. MATERIALS AND METHODS: Thirteen patients with Cushing disease and one with acromegaly underwent US during transsphenoidal surgery. Mechanically oscillating transducers (10 MHz [n = 8] or 15 MHz [n = 6]) mounted on a 15-cm long probe were used. RESULTS: Seven adenomas were definitely visualized, two were poorly seen, and four were overlooked. Small tumors (< 5 mm in diameter) tended to be hypoechoic; larger ones, hyperechoic. All four overlooked adenomas were imaged with the 15-MHz transducer. The cavernous sinuses and internal carotid arteries could be seen, but minimal invasion of the medial wall of the cavernous sinus could not. CONCLUSION: Pituitary microadenomas can be detected with transsphenoidal US; however, evaluation of larger series with instrumentation developed specifically for transsphenoidal application will be necessary to determine the ultimate value of this technique. PMID- 8208922 TI - Oscillatory motion of the normal cervical spinal cord. AB - PURPOSE: To determine the normal pattern of cervical spinal cord motion with measurement of cervical spinal cord velocity by means of phase-contrast magnetic resonance (MR) imaging. MATERIALS AND METHODS: Spinal cord velocity was measured in 11 healthy subjects with a modified gradient-echo pulse sequence on a conventional 1.5-T MR imaging system that generated phase images sensitive to slow motion. Prospective electrocardiogram gating was used to assess velocity as a function of the cardiac cycle. The accuracy of velocity measurements was estimated with images of a phantom moving at constant velocity. RESULTS: The cervical spinal cord moves with an oscillatory pattern in the craniocaudal direction. The maximum velocity (7.0 mm/sec +/- 1.4 [standard deviation]) in the caudal direction occurred approximately 109 msec +/- 20 after electrical cardiac systole. The maximum velocities in subsequent oscillations decreased toward zero before the next cardiac systole. CONCLUSION: The cervical spinal cord oscillates in a craniocaudal direction after each cardiac systole. PMID- 8208923 TI - Diagnosis of mesial temporal sclerosis with conventional versus fast spin-echo MR imaging. AB - PURPOSE: To test the accuracy of fast spin-echo (FSE) imaging versus that of double-echo conventional spin-echo (CSE) imaging in identification of the increased hippocampal signal intensity associated with mesial temporal sclerosis (MTS). MATERIALS AND METHODS: Thirty-four subjects who subsequently underwent anterior temporal lobectomy for intractable seizures and in whom the presence or absence of MTS was ascertained with certainty were imaged with CSE and FSE. Three blinded reviewers evaluated the first and second CSE images (CSE1 and CSE2) and the FSE images. RESULTS: CSE1 imaging had lower accuracy than FSE (P = .038) and CSE2 (P = .006) imaging. CSE2 imaging was slightly more accurate than FSE imaging (P = .048). Contrast-to-noise ratios were lower for CSE1 imaging than for CSE2 or FSE imaging (P < .001). CONCLUSION: The FSE sequence evaluated was more time efficient than CSE imaging but slightly less accurate. Therefore, substitution of this sequence for a CSE sequence seems unwarranted. PMID- 8208924 TI - Intracranial aneurysms: depiction on MR angiograms with a multifeature extraction, ray-tracing postprocessing algorithm. AB - PURPOSE: To compare a new method for postprocessing data, soft thresholding and depth cueing of unrestricted techniques (STANDOUT), with maximum intensity projection (MIP) for magnetic resonance (MR) angiograms of intracranial aneurysms. MATERIALS AND METHODS: Eighteen patients with 19 intracranial aneurysms were studied. Images generated with STANDOUT were compared with those of MIP for both three-dimensional (3D) time-of-flight (TOF) and 3D phase-contrast (PC) techniques. Images were assessed for detection of aneurysms, scored for delineation of aneurysmal features and overall MR angiographic characteristics, and compared with catheter angiograms. RESULTS: Both postprocessing techniques demonstrated aneurysms on most TOF and PC MR angiograms. Statistically significant improvement of aneurysmal features, aneurysmal neck definition, and delineation of adjacent arterial anatomy was seen on both TOF and PC MR angiograms with STANDOUT. Feature definition was most improved for smaller aneurysms. TOF and PC MR angiograms with STANDOUT showed improved elimination of artifactual intraluminal signal loss in normal large vessels, reduced artifactual narrowing of vessel caliber, and better small vessel delineation. CONCLUSION: STANDOUT has great benefits for postprocessing of intracranial MR angiograms, regardless of the technique of data acquisition. PMID- 8208925 TI - Snake wars. PMID- 8208926 TI - Vascularization of primary central nervous system tumors: detection with contrast enhanced transcranial color-coded real-time sonography. AB - PURPOSE: To study the potential of contrast material-enhanced transcranial color coded real-time sonography (TCCS) in detection of primary intracranial tumor vascularization. MATERIALS AND METHODS: Primary central nervous system (CNS) tumors in 28 patients were examined with TCCS before and during administration of a transpulmonary, stable, galactose, microparticle-based ultrasound (US) contrast agent. All patients underwent cranial computed tomography and magnetic resonance imaging; nine patients also underwent intraarterial digital subtraction angiography. RESULTS: All lesions were hyperechoic on B-mode US scans except one grade 2 astrocytoma. The location and extent of hyperechoic lesions correlated well with findings on CT scans and MR images. After injection of contrast material, color Doppler flow signals were seen in nine of 14 low-grade lesions and 14 of 14 high-grade lesions. High-grade malignant tumors always had atypical arterial and venous Doppler spectra with irregular distribution of Doppler shift and signal intensities; these atypical flow patterns were also detected in some low-grade tumors. CONCLUSION: In addition to depiction of primary CNS tumors in B mode, contrast-enhanced TCCS enables evaluation of vascularization associated with tumor parenchyma. PMID- 8208927 TI - Mammographic findings after stereotaxic biopsy of the breast performed with large core needles. AB - PURPOSE: To evaluate changes seen on mammograms obtained after large-core stereotaxic biopsy of the breast. MATERIALS AND METHODS: Twenty-seven patients underwent stereotaxic breast biopsy performed with large-core, 14-gauge needles. At least five core samples were obtained from each lesion. The mammograms obtained before biopsy were compared with those obtained 6 months later in the 24 patients in whom follow-up was performed. RESULTS: The only changes seen on the postbiopsy mammograms were due to tissue sampling (ie, fewer microcalcifications or defects were seen in areas of lesions from which tissue had been extracted). CONCLUSION: Large-core needle biopsy of the breast does not produce change or deformity that can be recognized on mammograms. Parenchymal scarring, architectural distortion, fat necrosis, or other identifiable changes seen after surgical biopsy of the breast are not seen after large-core, stereotaxic breast biopsy. PMID- 8208928 TI - Stability of malignant breast microcalcifications. AB - PURPOSE: To determine the frequency of stability in malignant microcalcifications and its relationship to specific histologic diagnoses. MATERIALS AND METHODS: During a 34-month period, microcalcifications were proved malignant in 182 patients referred for needle-guided biopsy. In 105 patients, the mammograms were compared with one or more than one previous mammogram. These patients were classified on the basis of interval change in two groups: those with stable and those with increasing or new microcalcifications. The histologic diagnoses were reviewed. RESULTS: Microcalcifications were stable for 8-63 months (mean, 25.4 months) in 26 patients (24.8%), only three (12%) of whom had invasive ductal carcinoma, which was found in 29 (37%) of the 79 patients with increasing or new microcalcifications. CONCLUSION: The odds for presence of invasive ductal carcinoma are statistically significantly lower (P < .025) among patients with stable microcalcifications than among those with increasing or new microcalcifications. Stability of indeterminate or suspicious microcalcifications is unreliable for exclusion of a diagnosis of malignancy. PMID- 8208929 TI - Non-Hodgkin lymphoma of the breast: imaging characteristics and correlation with histopathologic findings. AB - PURPOSE: To determine the imaging characteristics of non-Hodgkin lymphoma (NHL) of the breast and correlate these findings with histopathologic subtype. MATERIALS AND METHODS: The authors retrospectively reviewed records in 32 cases of histologically proved NHL in 29 women. Mammography was performed before biopsy in all cases, and breast sonography was performed before biopsy in eight. RESULTS: Mammary NHL was primary in 21 of the 32 cases (66%) and secondary in 11 (34%). Mammography revealed a solitary, uncalcified mass in 22 cases (69%), multiple masses in three (9%), and diffuse increased opacity with skin thickening in three (9%). Four cases (13%) had normal findings. Seven of the eight sonograms revealed masses, which were solitary in five and multiple in two. Histologic examination showed diffuse NHL in 26 cases (81%) and follicular NHL in six (19%). No mammographic or sonographic features were identified that helped distinguish primary from secondary disease or follicular from diffuse NHL. CONCLUSION: Although the imaging characteristics may suggest the possibility of breast NHL, none of the findings are pathognomonic. The imaging pattern of mammary NHL is unrelated to its histopathologic subtype. PMID- 8208930 TI - Dermal calcifications in fixed orientation: the tattoo sign. AB - Calcifications located in the dermis of the breast may appear indistinguishable from intramammary calcifications. The authors present a sign, called the tattoo sign, that can help radiologists identify dermal calcifications. When mammograms are compared, calcifications that maintain a fixed relationship to each other suggest a dermal location. This can be verified with standard techniques. Understanding the tattoo sign may help prevent unnecessary needle localization and biopsy procedures. PMID- 8208931 TI - Anterior clear space: how clear? How often? How come? AB - PURPOSE: To compare the opacity of the retrosternal clear space with that of the retrocardiac region on normal lateral chest radiographs, to measure the clear space, and to evaluate the reasons for these findings. MATERIALS AND METHODS: Left lateral chest radiographs and computed tomographic scans of 38 patients with normal studies were evaluated and the results were correlated. RESULTS: In 19 (50%) patients, retrosternal and retrocardiac opacity were equal. In 16 (42%), the retrosternal region was more opaque than the retrocardiac region (10 of 12 women, six of 26 men). The difference between the sexes was statistically significant (P = .002). In only nine (24%) patients was the anterior margin of the ascending aorta defined on the lateral study. Mean sternum-to-aorta distance in these patients was 29 mm. CONCLUSIONS: Retrosternal opacity greater than retrocardiac opacity on lateral chest radiographs is a frequent normal finding, especially in women. Sternum-to-aorta distance may be difficult to measure, and distance greater than 2.5 cm may be normal in some persons. PMID- 8208932 TI - Interpretation of subtle interstitial lung abnormalities: conventional versus film-digitized radiography. AB - PURPOSE: To evaluate the reliability of film-digitized radiography in detection of subtle interstitial lung abnormalities. MATERIALS AND METHODS: The differences in interpretation of conventional screen-film (SF) and film-digitized (FD) radiographs obtained in 80 patients were studied. Forty patients with subtle interstitial lung abnormalities and 40 patients with no lung abnormalities were selected. SF radiographs of all patients were digitized (spatial resolution, 0.175 mm; 2,000 x 2,000 pixels; 10 bits). Five chest radiologists and five residents evaluated the images with a five-level scale of confidence. Results were evaluated with receiver operating characteristic techniques. RESULTS: For the entire group, no statistically significant differences in performance were found between SF and FD radiographs. Chest radiologists performed better on SF radiographs (P = .003). For residents, no statistically significant differences were observed between the modalities. CONCLUSION: FD radiographs may be inadequate compared with SF radiographs in the diagnosis of subtle interstitial lung abnormalities. PMID- 8208933 TI - Open window thoracostomy, myoplasty, and epiploplasty for treatment of postpneumonectomy empyema: CT evaluation. AB - PURPOSE: To demonstrate the computed tomographic (CT) appearance of the postpneumonectomy space (PPS) after surgical treatment of postpneumonectomy empyema. MATERIALS AND METHODS: The authors retrospectively reviewed 22 CT scans obtained in 15 patients after open window thoracostomy (OWT) (n = 4), myoplasty (n = 12), and epiploplasty (n = 1). RESULTS: After uncomplicated OWT, the retracted PPS contained air and/or gauze without residual pleural fluid. After uncomplicated myoplasty, marked retraction of the operated hemithorax was observed. CT allowed localization of transposed muscle flaps and fatty tissue within the PPS. A moderate amount of fluid and air was present during the 1st month after surgery. After uncomplicated epiploplasty, the retracted PPS contained homogeneous tissue with characteristic fatty attenuation. Complications including recurrent empyema, recurrent bronchopleural fistula, aseptic fluid collection, necrosis and fatty transformation of muscle flaps, and tumor recurrence were accurately demonstrated. CONCLUSION: CT is useful in follow-up after surgical treatment of postpneumonectomy empyema because it permits accurate evaluation of the PPS. PMID- 8208934 TI - Reporting the "missed" radiologic diagnosis: medicolegal and ethical considerations. PMID- 8208935 TI - Chronic ankle instability: evaluation with MR arthrography, MR imaging, and stress radiography. AB - PURPOSE: To compare the efficacy of conventional magnetic resonance (MR) imaging, MR arthrography, and stress radiography in the detection of lateral collateral ligament abnormalities in patients with chronic ankle instability. MATERIALS AND METHODS: Seventeen patients with chronic lateral ankle instability underwent stress radiography, MR imaging, and MR arthrography after intraarticular injection of gadopentetate dimeglumine. Imaging findings were correlated with surgical findings. RESULTS: The anterior talofibular (ATF) ligament was torn in 14 patients, and the calcaneofibular (CF) ligament was torn in 10. MR arthrography was more accurate and sensitive in the detection of ATF tears than was MR imaging or stress radiography (P < or = .05). Associated injuries were detected with both MR imaging and MR arthrography. CONCLUSION: MR arthrography is a sensitive technique for detecting and staging tears of the lateral collateral ligaments. PMID- 8208936 TI - Imaging the pancreatic and biliary ducts with MR. PMID- 8208937 TI - Painful transient tibial edema. AB - PURPOSE: To report four cases of leg pain resembling transient bone marrow edema (TBME). MATERIALS AND METHODS: Four women aged 51-71 years had lower leg pain that regressed over 3-13 months. All patients underwent physical examination, clinical testing, radiography, scintigraphy, and magnetic resonance (MR) imaging. One patient underwent computed tomography; two underwent biopsy. RESULTS: All patients had tenderness at physical examination, and one had erythema and mild swelling over part of the leg. No laboratory results suggested systemic illness or infection. All had normal radiographs and abnormal bone scans, with increased radiopharmaceutical uptake in the tibial diaphyses. MR imaging showed decreased signal intensity with T1-weighting and increased signal intensity with inversion recovery. There were also signal intensity changes consistent with edema in the surrounding soft tissues. Biopsies showed focal marrow fibrosis and new bone formation with foci of devitalized bone. CONCLUSION: These cases resemble TBME but are unusual in their distribution. Whether they represent a previously undescribed clinical syndrome or a variant of TBME remains to be clarified. PMID- 8208938 TI - Healing flare in skeletal metastases from breast cancer. AB - PURPOSE: To identify the frequency, characteristics, and prognostic significance of scintigraphically detected healing flare in patients with breast cancer metastatic to bone. MATERIALS AND METHODS: Findings on bone scans and concomitant radiographs of 1,188 patients were reviewed. Bone metastases occurred in 426 patients. Outcomes of 101 patients (aged 21-71 years) with skeletal metastases were correlated with typical scintigraphic and radiographic features. RESULTS: Healing flare with increased radiotracer uptake and radiographically demonstrated sclerotic changes in osteolytic or mixed skeletal metastases were prospectively identified in 12% of patients with skeletal metastases. Healing flare was detected 3.2 months +/- 1.4 after initiation of hormonal treatment or chemotherapy. Skeletal metastatic activity stabilized on bone scans within 6.2 months +/- 3.0. Patients with healing flare did not survive longer than patients without healing flare but with stable metastases after treatment (3.3 years +/- 2.0 vs 3.9 years +/- 1.6). CONCLUSION: Scintigraphically detected healing flare represents a favorable response to therapy not associated with increased survival. PMID- 8208939 TI - Acromioclavicular joint fluid: determination of clinical significance with MR imaging. AB - PURPOSE: To determine the clinical significance of fluid in the acromioclavicular (AC) joint. MATERIALS AND METHODS: A total of 108 patients with clinical shoulder problems and 16 volunteers underwent MR imaging with a 1.5-T unit. Coronal T1- and T2-weighted images were evaluated for the presence of AC joint fluid, glenohumeral joint fluid, and AC joint osteophytes. Medical records were reviewed for the presence of clinical signs and symptoms. RESULTS: AC joint fluid was commonly seen in the patients (67%) but was rare in the volunteers (12%). The presence of AC joint fluid was associated with advancing patient age, presence of osteophytes, and fluid in the glenohumeral joint. AC joint fluid was not associated with focal tenderness, prior corticosteroid injections, history of trauma, findings of impingement, evidence of rotator cuff tear on MR images, or gender. CONCLUSION: AC joint fluid appears to be an asymptomatic manifestation of osteoarthritis. PMID- 8208940 TI - Age-related changes in marrow distribution in the shoulder: MR imaging findings. AB - PURPOSE: To define age-specific patterns of distribution of red and yellow marrow about the shoulder. MATERIALS AND METHODS: Red and yellow marrow distribution was reviewed on magnetic resonance images of 189 subjects aged 15-69 years. Double echo and fast spin-echo, gradient, and short inversion time inversion recovery pulse sequences were used. The acromion, glenoid, and proximal humeral epiphysis, metaphysis, and diaphysis in each shoulder were graded semiquantitatively and qualitatively. RESULTS: There was a wide variation in the normal pattern of red yellow marrow distribution both among subjects and among locations. All five anatomic locations showed an orderly progression from greater to lesser amounts of red marrow with increasing age. Many of the subjects had focal subchondral red marrow in the epiphysis, which was associated with patient age (P = .0001) and gender (P = .04). CONCLUSION: Knowledge of normal patterns of marrow distribution can prevent their being misinterpreted as marrow-based disease. PMID- 8208942 TI - The changing role of MR imaging in the evaluation of acute optic neuritis. PMID- 8208941 TI - Scapholunate interosseous ligament of the wrist: MR appearances in asymptomatic volunteers and arthrographically normal wrists. AB - PURPOSE: To determine if the carpal scapholunate ligament (SLL) can be consistently visualized with commercial magnetic resonance (MR) imaging techniques and to establish the normal range of MR appearances of the SLL as a basis for comparison with SLL tears. MATERIALS AND METHODS: MR imaging helped identify and characterize the appearance of the SLL in 80 wrists with presumably normal SLLs (54 wrists in 27 asymptomatic volunteers and 26 patients with normal arthrograms). A dual-echo, gradient-echo technique was used. RESULTS: The SLL was visible in all 80 wrists and was seen on an average of almost four sections. It was delta-shaped in 72 wrists and linear in eight; there was absent signal intensity in 63% or intermediate signal intensity traversing all or part of the SLL in 37%. Distribution and extent of hyaline cartilage signal intensity at the insertion sites into the scaphoid and lunate bones were variable but related to the location within the SLL. CONCLUSION: The SLL can be consistently identified, but the normal variation in the MR appearance of the lunotriquetral ligament must be appreciated when evaluating wrists with suspected SLL tears. PMID- 8208943 TI - Mitochondrial encephalomyopathy: correlation of P-31 exercise MR spectroscopy with clinical findings. AB - PURPOSE: To evaluate the sensitivity of standardized exercise phosphorus-31 magnetic resonance (MR) spectroscopy in screening for subclinical muscle involvement in mitochondrial encephalomyopathy and to estimate if changes seen at biopsy have functional consequences. MATERIALS AND METHODS: Exercise MR spectroscopy was performed in 52 examinations of 18 healthy volunteers and 14 patients with defects of mitochondrial respiratory chain enzymes. Calculation and kinetic analysis of the phosphocreatine (PCr) index and pH time courses were standardized with a microcomputer program. RESULTS: PCr index scores and conventional test scores matched in 10 of 14 cases. No obvious correlation existed between pH parameters and clinical score. Muscle affection, according to pH parameter score, was rated moderate (n = 3), severe (n = 1), or maximum (n = 2) in six of 14 cases in which clinical test scores showed only mild affection. CONCLUSION: Exercise MR spectroscopic PCr index parameters provide diagnostic information on skeletal muscle involvement in patients with mitochondrial encephalopathy. The sensitivity of the PCr index parameter seems equal or superior to that of conventional diagnostic tests. The role of pH parameters, however, has yet to be defined. PMID- 8208944 TI - Development of stenoses in transjugular intrahepatic portosystemic shunts. AB - PURPOSE: To evaluate the frequency and significance of stenoses or occlusions developing within transjugular intrahepatic portosystemic shunts (TIPS) and identify predictive factors. MATERIALS AND METHODS: Medical records of 52 patients who underwent TIPS placement between September 1991 and October 1993 were reviewed. Various shunt parameters were correlated with the development of shunt abnormalities. Findings at follow-up portography and frequency of variceal bleeding and paracentesis were also noted. RESULTS: Twenty-four patients were followed up for at least 6 months. In eight patients, stenoses developed within 6 months; one shunt occluded. No clear correlations were found between shunt parameters and development of shunt abnormalities. Two of four patients with recurrent variceal bleeding had associated shunt abnormalities. The frequency of stenosis of TIPS was high. CONCLUSION: Early detection and prompt revision of stenotic shunts may decrease the frequency of recurrent variceal bleeding and ascites. PMID- 8208945 TI - Variceal hemorrhage: efficacy of transjugular intrahepatic portosystemic shunts created with Strecker stents. AB - PURPOSE: To evaluate the efficacy of transjugular intrahepatic portosystemic shunts (TIPS) in treatment of variceal hemorrhage. MATERIALS AND METHODS: Forty five patients with cirrhosis underwent TIPS placement for treatment of acute (n = 12) or recurrent (n = 33) variceal hemorrhage. Shunts were created with Strecker stents. RESULTS: Shunts were established by deployment of stents in 42 patients. The portosystemic pressure gradient decreased from an average of 20.4 mm Hg +/- 5.4 to 9.2 mm Hg +/- 4.1. Complications included hepatic failure (n = 1), acute shunt thrombosis (n = 2), right jugular vein thrombosis (n = 1), bacteremia (n = 1), and stent misplacement (n = 1). Acute bleeding was controlled in 12 patients. The 30-day mortality rate was 2%; four other patients have since died. During follow-up (mean, 8.9 months), variceal bleeding recurred in six patients. Hepatic encephalopathy developed in six patients. Shunt stenosis or occlusion requiring further intervention occurred in 20 patients. CONCLUSION: TIPS are safe and effective in treatment of variceal hemorrhage; however, secondary interventions are often required to preserve shunt function. PMID- 8208946 TI - Sonography of the fetal posterior fossa: false appearance of mega-cisterna magna and Dandy-Walker variant. AB - PURPOSE: To establish that incorrect scanning of the fetal posterior fossa may falsely create the appearance of a mega-cisterna magna (MCM) or Dandy-Walker variant (DWV). MATERIALS AND METHODS: After routine sonography, 100 consecutive fetuses (gestational age range, 25-40 weeks) without abnormality underwent additional posterior fossa scanning in an attempt to create the appearance of an MCM (anteroposterior diameter larger than 10 mm) or DWV. Sonograms were obtained in a plane inferior to or angled more coronally than the routine axial plane. RESULTS: The posterior fossa was depicted in 93 fetuses. Pseudo-MCM occurred in 35 (38%) of 93 fetuses: 12 (30%) of 40 fetuses aged 25.0-29.9 weeks, 11 (50%) of 22 fetuses aged 30.0-34.9 weeks, and 12 (39%) of 31 fetuses aged 35.0-40.0 weeks. Pseudo-DWV occurred in 40 (43%) of 93 fetuses: 20 (50%) of 40 fetuses aged 25.0 29.9 weeks, 12 (55%) of 22 fetuses aged 30.0-34.9 weeks, and eight (26%) of 31 fetuses aged 35.0-40.0 weeks. CONCLUSION: Sonography of the posterior fossa in an angled semi-coronal plane should be avoided because it may create an appearance that mimics an abnormality. PMID- 8208947 TI - Brief history of comparative clinical trials in radiation oncology: perspectives from the silver anniversary of the Radiation Therapy Oncology Group. PMID- 8208948 TI - Three-dimensional US of the fetus. Work in progress. AB - PURPOSE: To develop a system for three-dimensional (3D) ultrasonography (US) that readily interfaces with conventional equipment and to apply this system to fetal imaging. MATERIALS AND METHODS: An acquisition system based on transputer technology records from the video output of standard clinical scanners was interfaced with a position-sensing device, one component of which was attached to the US probe. The method differs from other 3D US methods as any conventional probe may be used, freehand scanning is possible, and no line-of-sight limitations operate. Such scanning was performed of 25 fetuses with gestation ages of 7-30 weeks. RESULTS: Acquisition typically took 3-5 seconds. Acquisition and reconstruction were successful in 17 of 25 cases and were easiest to perform in the first and second trimester. Surface rendering revealed anatomic detail that was not depicted with two-dimensional scanning. CONCLUSION: The technique has the potential for recording complete anatomic studies for review and visualization of detail that is difficult to perceive on conventional US scans. PMID- 8208949 TI - Posterior urethral valve: transperineal US for imaging and diagnosis in male infants. AB - PURPOSE: To compare routine pelvic and transperineal scanning in the ultrasonographic (US) diagnosis of posterior urethral valve (PUV). MATERIALS AND METHODS: Longitudinal and transverse transperineal views were obtained in addition to routine renal and transvesicle views in the prospective US evaluation of 10 male infants (aged 2 days to 6 weeks) clinically suspected of having PUV. High-frequency (5.0- and 7.5-MHz) transducers were used. RESULTS: Five of the boys proved to have PUV. Each had urethral dilation clearly imaged at transperineal US. Only two of these boys had urethral dilatation imaged with the transvesicle approach. In three of the boys, a linear area of echogenicity, consistent with a valve, was imaged, but only with the transperineal approach. The other five boys had no urethral dilatation noted at transperineal or transvesicle US and proved to not have PUV. CONCLUSION: Transperineal imaging can aid in the diagnosis of PUV at US. Transperineal US may enable imaging of the valve itself. PMID- 8208951 TI - Spontaneous reduction of intussusception: verification with US. AB - PURPOSE: To report cases of spontaneous reduction of intussusception. MATERIALS AND METHODS: The authors reviewed the clinical and imaging findings in four patients with intussusception. Patients ranged in age from 3 to 7 months and were seen over a 12-year period. RESULTS: Intussusception was diagnosed with ultrasound (US) in all four patients; however, when enema studies were performed, intussusception was not identified. Repeat US also failed to demonstrate the presence of an intussusception, and all four patients showed concomitant rapid resolution of symptoms. CONCLUSION: Spontaneous reduction of intussusception is probably more common than is generally thought, and its documentation was facilitated with US. It is likely that spontaneously reduced intussusception will be documented more frequently in the future. PMID- 8208950 TI - Tunneled central venous access catheter placement in the pediatric population: comparison of radiologic and surgical results. AB - PURPOSE: To compare the success and infection rates of radiologic placement with those of surgical placement of tunneled central venous access catheters (TCVACs) in infants and small children. MATERIALS AND METHODS: In 17 pediatric patients, TCVACs were placed with vascular access under ultrasound or fluoroscopic guidance in the radiology department. In 29 other patients, TCVACs were placed with percutaneous puncture or surgical cutdown in the surgery department. RESULTS: Two (11%) of 18 attempts at radiologic placement were unsuccessful; six (38%) of the 16 radiologically placed catheters necessitated removal because of dislodgment, malfunction, or infection; six (38%) were electively removed; and four (25%) still function. Eight (23%) of 35 attempts at surgical placement were unsuccessful; 17 (63%) of the 27 surgically placed catheters required removal because of dislodgment, malfunction, or infection; nine (33%) were electively removed; and one (4%) still functions. CONCLUSION: The success and infection rates of radiologic placement of TCVACs were similar to those of surgical placement. Radiologic placement required fewer attempts and was slightly less expensive. PMID- 8208952 TI - MR-guided biopsy of suspect breast lesions with a simple stereotaxic add-on device for surface coils. AB - A guiding attachment is described that transforms a conventional magnetic resonance (MR) imaging surface coil into a stereotaxic biopsy unit. Eight patients, aged 38-66 years (mean, 54 years), with suspect breast lesions detected exclusively at contrast material-enhanced MR imaging underwent MR-guided needle biopsy with this unit. Diagnostic material was successfully aspirated in all patients (four carcinomas, three fibroadenomas, and one intraductal hyperplasia), and the diagnosis was subsequently confirmed at surgical biopsy. This technique promises to increase the diagnostic specificity for lesions seen solely at MR imaging. PMID- 8208953 TI - Three-dimensional US and volumetric assessment of the prostate. AB - The authors demonstrate a method for constructing three-dimensional (3D) images of the prostate based on standard two-dimensional ultrasonic (US) images. Transverse US images of the prostate in six patients (aged 61-83 years) and 10 water-filled balloon phantoms were recorded at video rates by manually withdrawing a biplane transrectal probe at a constant speed. Data acquisition time of the images was less than a minute. Typically, 50-70 scans of 0.2-0.5-mm thick cross sections were acquired. Postprocessing of these data enabled lifelike 3D visualization of the gland and accurate measurement of its volume. PMID- 8208954 TI - Management of probably benign lesions of the breast. PMID- 8208955 TI - Use of 2-[F-18]-fluoro-2-deoxy-D-glucose PET to locate parathyroid adenomas in primary hyperparathyroidism. PMID- 8208956 TI - Radiculopathy, radicular pain, radiating pain, referred pain: what are we really talking about? PMID- 8208957 TI - Bedside chest radiography. PMID- 8208958 TI - Modified biliary drainage catheter. PMID- 8208959 TI - Percutaneous hot saline injection therapy for hepatocellular carcinoma. PMID- 8208960 TI - Perioperative implantation of iridium-192 as the boost technique for stage I and II breast cancer: results of a 10-year study of 655 patients. AB - PURPOSE: To assess the efficacy of perioperative implantation of iridium-192 for stage I and II breast cancer. MATERIALS AND METHODS: The authors retrospectively reviewed findings from 655 patients with stage I and II cancer treated with conservative surgery and Ir-192 implantation between 1982 and 1992. Hollow plastic tubes were placed in the tumor bed as a single- or double-plane implant at lumpectomy. Ribbons with Ir-192 seeds were inserted into the tubes 4-6 hours later. The Ir-192 was left in place for approximately 50 hours. External-beam irradiation was given to the whole breast 10-14 days later. RESULTS: Follow-up ranged from 2 to 146 months. The local control at 10 years for stage I and II disease was 93% and 87%, respectively. The 10-year actuarial survival rate was 92% +/- 1 for stage I disease and 72% +/- 4 for stage II disease. The rate of survival with no evidence of disease for stage I and II disease combined was 82% +/- 1 at 5 years and 75% +/- 3 at 10 years. CONCLUSION: Perioperative implantation produced excellent local control equal to that with electron-beam therapy. PMID- 8208961 TI - Prostate cancer: are racial differences in clinical stage and survival explained by differences in symptoms? AB - PURPOSE: To better understand racial differences in data for patients referred for definitive treatment of biopsy-proved adenocarcinoma of the prostate gland. MATERIALS AND METHODS: Two groups of patients were defined for further analysis. Group 1 comprised all patients who received definitive external beam irradiation of prostatic carcinoma; group 2 comprised all patients with prostatic carcinoma referred between January 1988 and December 1992 for examination at the first clinical indication of adenocarcinoma of the prostate. All patients were evaluated for age, race (black vs white), differentiation of tumor, date of diagnosis, and clinical stage. RESULTS: In group 1, black patients were significantly younger and presented with disease at higher clinical stage but equivalent grade and survival compared with white patients. In group 2, black patients were significantly younger and had similar differentiation of tumor but with significantly higher clinical stage compared with white patients and more often had obstructive symptoms and less often had been screened for elevated prostate-specific antigen levels. CONCLUSION: Black patients should undergo earlier screening for prostate cancer. PMID- 8208962 TI - Differentiation of adrenal masses with MR imaging: comparison of techniques. AB - PURPOSE: To determine the efficacy of various magnetic resonance (MR) imaging sequences for the differentiation of adrenal masses. MATERIALS AND METHODS: Fifty three adrenal masses in 46 patients (adenomas, metastases, myelolipomas, hemorrhages, and pheochromocytomas) were evaluated by means of T1-, T2-, and T2* weighted sequences, calculated T2 values, chemical shift imaging techniques, and dynamic contrast material-enhanced imaging. The Student t test and receiver operating characteristic analysis were used to evaluate the differences in the groups of masses. RESULTS: Analysis of the chemical shift-induced signal intensity of the adrenal masses and the T2*-weighted sequence enabled differentiation of adenomas, metastases, and pheochromocytomas. Adenomas and pheochromocytomas were also differentiated by means of a heavily T2-weighted sequence. Signal intensity values for all masses overlapped. CONCLUSION: Although a chemical shift imaging technique and a T2*-weighted sequence helped correctly differentiate among the groups of adrenal masses, the degree of overlap suggests that it is still difficult to evaluate disease in individual patients. PMID- 8208964 TI - Algorithms: the new math in medicine. PMID- 8208963 TI - Staging of prostate cancer: results of Radiology Diagnostic Oncology Group project comparison of three MR imaging techniques. AB - PURPOSE: To assess accuracy of three different magnetic resonance (MR) imaging techniques, including the endorectal coil, in staging prostate cancer. MATERIALS AND METHODS: MR imaging was performed in 213 patients with prostate cancer with a conventional body coil, with fat suppression and a body coil, and with an endorectal coil. Radiologists identified tumor invasion into periprostatic tissues, neurovascular bundles, and seminal vesicles. Each technique was evaluated separately, and in a subset of 74 patients the three techniques were evaluated together. Images obtained with the two body-coil techniques were read in combination with images obtained with the endorectal coil (combination A) and alone (combination B). RESULTS: Overall accuracy for conventional body-coil, fat suppressed body-coil, and endorectal-coil MR was 61%, 64%, and 54%, respectively. Overall group accuracy for combinations A and B was 57% and 61%. Considerable interreader variability was found for combination A. CONCLUSION: No technique was highly accurate for staging early prostate cancer. Individual radiologists did achieve a high degree of staging accuracy with the endorectal-coil and body-coil combination. PMID- 8208965 TI - Setting appropriateness guidelines for radiology. PMID- 8208966 TI - Female pelvis: impact of MR imaging on treatment decisions and net cost analysis. AB - PURPOSE: To determine the impact of gynecologic magnetic resonance (MR) imaging on treatment decisions and net cost. MATERIALS AND METHODS: Sixty-nine consecutive women were referred for 70 pelvic MR imaging examinations. Diagnosis and treatment plans were obtained from referring physicians before and immediately after they were given verbal reports of MR imaging results. Outcome regarding treatment and symptoms was obtained at a mean follow-up of 10.9 months. RESULTS: Of 49 (71%) patients originally recommended for surgery, 36 (73%) either did not undergo surgery or less invasive surgery was performed. In 58 (84%) patients, the treatment performed was that recommended after performance of MR imaging. Symptoms resolved in 57 (83%) patients. Use of MR imaging resulted in an overall savings of $63 per patient ($1,736 per patient originally recommended for surgery). CONCLUSION: Use of pelvic MR imaging in diagnosis of some gynecologic diseases may alter treatment, decrease the number of invasive surgical procedures performed, and reduce total health care expenditures. PMID- 8208967 TI - Stage IIb cervical carcinoma: MR evaluation of effect of intraarterial chemotherapy. AB - PURPOSE: To evaluate magnetic resonance (MR) imaging in assessment of tumor response after intraarterial chemotherapy (IAC) in cervical carcinoma. MATERIALS AND METHODS: MR images of 19 patients who underwent IAC because of stage IIb cervical carcinoma were prospectively analyzed and compared with pathologic findings. Three courses of IAC were administered, and MR images were obtained before and after treatment. Extent of reduction of tumor volume determined eligibility for surgery. MR images of 17 patients who were candidates for surgery were correlated with pathologic specimens. RESULTS: Average reduction in tumor volume was 88.5%. Response to IAC was complete in seven patients, partial in 11, and minor in one. MR imaging findings after IAC correlated well with pathologic findings. CONCLUSION: MR imaging is useful in assessment of tumor response to IAC and provides criteria for decision making with regard to further radiation or surgical therapy. PMID- 8208969 TI - Breath-hold MR cholangiopancreatography with a long-echo-train fast spin-echo sequence and a surface coil in chronic pancreatitis. AB - PURPOSE: To assess heavily T2-weighted breath-hold magnetic resonance cholangiopancreatography (MRCP) for imaging the pancreatic duct in patients with chronic pancreatitis. MATERIALS AND METHODS: Thirty-nine patients with chronic pancreatitis were examined with a breath-hold fast spin-echo (FSE) sequence employing an echo train length of 32 and with a surface coil. Results were compared with those of endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: MRCP showed the head, body, and tail of the pancreatic duct well in 79%, 64%, and 53% of cases, respectively. Agreement between MRCP and ERCP was 83%-92% in cases of ductal dilatation, 70%-92% in cases of ductal narrowing, and 92%-100% in cases of filling defects. Interobserver variation was low (kappa > 0.5) for most findings. CONCLUSION: Breath-hold MRCP with an FSE technique depicts the pancreatic duct well in patients with chronic pancreatitis and demonstrates narrowing, dilatation, and filling defects with moderate to high accuracy. PMID- 8208968 TI - Interactive method of informing patients of the risks of intravenous contrast media. AB - PURPOSE: To evaluate interactive computer-based informed consent for use of contrast material versus the same information in a written format. MATERIALS AND METHODS: Patients (n = 160) referred for radiologic examination with intravenous contrast material were block randomized (sex, age, and previous exposure to contrast material) into two groups and were provided either written or computer based (video) informed consent. RESULTS: The female patients in the video group scored better on the test than those in the group with the written consent form. Male patients attained equivalent scores with both types of consent. The video took an average of 1.6 minutes longer to complete, probably because the majority of patients chose to be informed of every risk of intravenous contrast material. CONCLUSION: This project demonstrates that a video format for informed consent before use of intravenous contrast material offers a good alternative to the written consent form. PMID- 8208970 TI - F-18 fluorodeoxyglucose PET in vivo evaluation of pancreatic glucose metabolism for detection of pancreatic cancer. AB - PURPOSE: To evaluate positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose (FDG) for detection of pancreatic cancer compared with computed tomography (CT) and ultrasonography (US). MATERIALS AND METHODS: Forty patients with suspected pancreatic cancer underwent static PET after intravenous injection of 150-300 MBq FDG. Focal FDG accumulation was regarded as a sign of malignancy and was quantitated by calculating differential uptake ratios (DURs) and tumor-liver ratios (TLRs). RESULTS: Malignancy was histologically proved in 27 patients. PET helped correctly classify 25 of 27 malignant conditions and 11 of 13 benign disorders. DUR and TLR were statistically significantly higher in malignant compared with benign disease (P < .01). False-negative findings were obtained in patients with insulin-dependent diabetes. False-positive findings were noted in a patient with retroperitoneal fibrosis and in one with pancreas divisum with chronic pancreatitis. PET was superior to CT and US in detection of lymph node metastases (13 of 17 vs three of 17 or one of 15, respectively. CONCLUSION: FDG PET has the potential to improve the detection of lymphadenopathy and the differential diagnosis of pancreatic masses. PMID- 8208971 TI - Extraserosal invasion in advanced gastric cancer: evaluation with MR imaging. AB - PURPOSE: To evaluate the usefulness of magnetic resonance (MR) imaging in the diagnosis of extraserosal invasion in advanced gastric cancer. MATERIALS AND METHODS: MR imaging was performed in 48 patients with advanced gastric cancer, and the results were correlated with the histopathologic findings. Images perpendicular to the gastric wall with cancer were obtained with spoiled gradient recalled acquisition in the steady state (GRASS). The degree of serosal invasion was classified on the basis of the appearance of a low-signal-intensity band around the lesion. RESULTS: Advanced gastric cancer appeared as a thickened wall of high signal intensity after the administration of contrast material. A low signal-intensity band disappeared or showed irregularity in the area of extraserosal invasion by the gastric cancer. The MR imaging-determined grade correlated with the histopathologic findings for 11 of 14 (79%) pT2 tumors, 23 of 24 (96%) pT3 tumors, and eight of 10 (80%) pT4 tumors. The overall accuracy was 88%. CONCLUSION: Presence of a low-signal-intensity band at MR imaging is useful for the preoperative evaluation of serosal invasion. PMID- 8208972 TI - Abdominal CT findings in sarcoidosis: radiologic and clinical correlation. AB - PURPOSE: To estimate the prevalence of abdominal computed tomographic (CT) findings in sarcoidosis and to correlate these findings with those at chest radiography, clinical status, and level of angiotensin converting enzyme (ACE). MATERIALS AND METHODS: Abdominal CT examinations in 59 patients with sarcoidosis were evaluated for adenopathy, liver and spleen size, and discrete lesions within the liver or spleen. RESULTS: Extensive adenopathy was seen in 10% of patients. Marked hepatic and splenic enlargement was seen in 8% and 6%, respectively. Nodules were seen in the spleen in eight (15%) patients and in the liver in three (5%). Although liver size, spleen size, and adenopathy were directly related (P < .0001), the presence of nodules was not strongly related to organ size. Abdominal CT findings were related to clinical status and elevated ACE levels but not to chest radiographic stage. CONCLUSION: Marked abdominal CT findings are uncommon in sarcoidosis and correlate with disease activity but not chest radiographic stage. PMID- 8208973 TI - Salivary gland tumors: pretherapy evaluation with PET. AB - PURPOSE: To determine whether positron emission tomography (PET) can help differentiate benign from malignant lesions of the salivary glands before surgery. MATERIALS AND METHODS: Masses of the salivary glands were examined in 26 patients by means of computed tomography, magnetic resonance imaging, PET, biopsy (n = 18), and surgery. Contiguous PET scans were obtained from the midcranium to the lower chest 45 minutes after administration of 370 MBq (10 mCi) of fluorine 18 fluorodeoxyglucose (FDG). Standard uptake values (SUVs) were determined for all suspect lesions and for normal parotid glands and cerebellum. RESULTS: All lesions were visualized, and all but two showed some increase in FDG uptake. PET findings helped correctly differentiate benign from malignant masses in 18 (69%) but were false-positive for malignancy in eight (31%). SUV analysis, lesion-to normal SUV ratios, and lesion-to-cerebellar SUV ratios also failed to differentiate the lesions. CONCLUSION: FDG PET is not useful in classifying salivary gland tumors as benign or malignant. PMID- 8208974 TI - Review of carbamazepine-induced hyponatremia. AB - 1. Carbamazepine (CBZ), a commonly prescribed medication in psychiatry and neurology, produces deleterious side effects with an incidence rate ranging from 33-50%; although most of these side effects are mild, transient, and reversible. CBZ-induced hyponatremia is a moderately well described side effect and may be responsible for some of the more highly reported signs and symptoms associated with CBZ adverse effects. 2. Data from case reports and clinical studies are examined to ascertain the characteristics of CBZ-induced hyponatremia. Predisposing risk factors such as: age, dosage/level of CBZ, and polypharmacy have been explored in numerous clinical studies; however, minimal consensus has been found regarding both dosage/level of CBZ and polypharmacy as a predisposing risk factor, whereas age is most probably not a predisposing risk factor in CBZ induced hyponatremia. 3. Mechanistic studies, both clinical and basic science, also fail to acknowledge the mechanism for the antidiuretic effect of CBZ. The most probable mechanism involves an alteration in either the sensitivity or set point of the osmoreceptor. PMID- 8208975 TI - Brofaromine in endogenous depression. AB - 1. Recently, a new generation of monoamine oxidase (MAO) inhibitors has been developed which selectively and reversibly inhibit MAO-A activity. 2. One of these compounds, called brofaromine, has been administered in subjects suffering from endogenous depression, revealing antidepressive efficacy in a majority of them without inducing serious adverse events. 3. The results obtained so far suggest that brofaromine might be effective in endogenous depressed patients who failed to respond to tricyclic antidepressants. PMID- 8208976 TI - Fluoxetine efficacy in treatment resistant depression. AB - 1. As many as 30% of depressed patients fail to respond to antidepressant drug therapy, and at least 60%-75% will not achieve complete recovery. Recently, several studies have suggested that newer, "second generation" antidepressants might be beneficial in treatment resistant depression (TRD). In the present study the authors examined the potential utility of fluoxetine in TRD by comparing its efficacy in patients with and without a prior history of antidepressant response. 2. 149 patients with MDD received fluoxetine 20mg daily for a minimum of 5 weeks: 43 (29%) had never responded to drug therapy (TRD patients), 41 (28%) did have a prior drug response (non-TRD patients) and 65 (44%) had never received any antidepressant treatment. Clinical response was defined as a > or = 50% reduction in baseline Hamilton Depression Rating score plus a final score < 7. 3. Compared to non-TRD patients, the TRD patients were more likely to have unipolar depression (p = 0.002), a chronic episode of > 2 years duration (p < 0.0001), a later age of illness onset (p < 0.0001), fewer prior episodes (p < 0.0001) and fewer prior drug treatments (p = 0.04). Overall, the response rate to fluoxetine was slightly greater in the non-TRD patients (76%) compared to the TRD patients (56%); however, this difference did not achieve statistical significance. 4. The present observations suggest that fluoxetine treatment of adequate duration may be beneficial for some patients with a prior history of refractory depression. PMID- 8208977 TI - P300 differences between non-alcoholic young men at average and above-average risk for alcoholism: effects of distraction and task modality. AB - 1. P300 event-related electroencephalographic potentials were recorded from 79 young adult males, cross-classified with respect to the presence/absence of a family history of alcoholism (FHA) and the presence/absence of a personal history of antisocial personality (ASP) disorder. P300s were elicited using visual and auditory oddball tasks. Each oddball task was repeated with a tracking task added as a distractor. 2. In general, distraction increased the latencies and reduced the amplitudes of P300s elicited by the oddball stimuli. The P300 latency increase occurred only in low risk ASP- and FHA- groups. There was no adaptive increase in P300 latency in the higher risk ASP+ and FHA+ groups. 3. Group differences in P300 were restricted to visual tasks. No interpretable group differences in P300 latency or amplitude were found during the auditory tasks. PMID- 8208978 TI - Schizophrenia and substance abuse: the interface. AB - 1. Starting from the hypothesis that schizophrenia is not a defined disease entity but may be part of a variety of "anomalous need disorders", the goal of our study (a sample of 30 patients) was to establish whether schizophrenia and substance abuse are caused by completely different factors or, on the contrary, are generated by similar processes. 2. The prevailing tendency to substance abuse and of a depression phase, that may be hardly elaborated, in this sample of patients with positive symptoms led us to a common denominator of the two disorders: a lacking structure where the symptom would substitute the defective element. PMID- 8208979 TI - Lithium ratio, phospholipids and the incidence of side effects. AB - The main aims of our Lithium Centre, which has been operating since 1985, are as follows: 1. the treatment of affective disorders and particularly the recurrent ones; 2. the emphasis of the Li-ratio as a predictive index of therapeutic effects on the one hand, and of the appearance of side effects on the other hand; 3. the prevention and pharmacological control of side effects and research about their mechanism of arising.; 4. organization of a computerized bibliographic service. PMID- 8208980 TI - Subtypes of negative symptoms: the primary subtype in schizophrenic and non schizophrenic patients. AB - 1. The specificity of negative symptoms remains an open question and requires further research. 2. Subtyping negative symptoms has been showed to be a very relevant point for the identification of primary negative symptoms and for their pharmacotherapy. Negative symptoms as a whole have been demonstrated in schizophrenic and non-schizophrenic patients, but these studies did not report about the primary and secondary subtypes. 3. The present study is the first one investigating primary negative symptoms in schizophrenic and non-schizophrenic patients. 84 consecutively admitted psychiatric patients have been studied 5 years after their discharge. 4. All negative symptoms (including the primary subtype) according to Carpenter (Kirkpatrick et al. 1989) and Andreasen (Andreasen 1981) could be identified in all diagnostic groups. PMID- 8208981 TI - Symptoms of premenstrual syndrome as a function of beta-endorphin: two subtypes. AB - 1. Forty six women presenting with symptoms of premenstrual syndrome (PMS) were studied. Ages ranged from 21 to 32. All women answered a questionnaire based on DSM-III-R criteria. They then had serum beta-endorphin levels drawn on day 1 and day 20 of their menstrual Cycle. 2. Beta-endorphin levels were compared with symptom presentation. Such symptoms as anxiety, food cravings and physical discomfort were associated with significant decline in beta-endorphin. Other symptoms were found equally distributed in both groups. The existence or absence of beta-endorphin decline in specific PMS subgroup was postulated. PMID- 8208982 TI - Serotonergic function in panic disorder: endocrine responses to D-fenfluramine. AB - 1. Prolactin and cortisol responses to d-fenfluramine were measured in 16 patients with DSM-III-R panic disorder and 14 normal controls. 2. Patients showed a greater mean prolactin response than controls but the difference between groups was not statistically significant (P > 0.05, MANOVA). 3. No consistent differences were observed between patients and controls with respect to cortisol responses (P > 0.05, MANOVA). 4. The results do not support the hypothesis of hypersensitive post-synaptic serotonin receptors in patients with panic disorder. 5. Studies in larger groups are necessary to confirm the trend and to explore receptor subtype sensitivity. PMID- 8208983 TI - Correlation of clinical response (PANSS) and plasma levels of haloperidol and reduced haloperidol in schizophrenia. AB - 1. The authors attempted to correlate plasma concentrations in H/rH and clinical efficacy from 8 schizophrenic patients (DSM IIIR) on H. 2. No significant correlations were found between H, rH plasma levels and positive and negative subscale for each patient. 3. The authors observed an opposite evolution concerning the mean results between plasma concentrations and PANSS total score. PMID- 8208984 TI - L-sulpiride in young and elderly negative schizophrenics: clinical and pharmacokinetic variables. AB - 1. Clinical activity, tolerability and kinetic profile of L-sulpiride (200-300 mg/die p.o.) in relation to age, in 14 chronic schizophrenic in patients diagnosed according to DSM III-R, typed as negative forms, were studied. 2. The drug showed its efficacy in negative forms of schizophrenia, without any significant difference between negative and positive symptoms even if productive symptom scores were quite low already in pre-treatment condition. 3. No more side effects (anticholinergic and extrapyramidal) in elderly patients compared to young/adult ones were reported. 4. No significant differences between young/adult and elderly patients for the various pharmacokinetic parameters (t1/2, AUC, Cmax, Tmax, Vd and Cl), after acute and multiple dosing, were observed. PMID- 8208985 TI - Moclobemide (Aurorix) in primary major depression. AB - 1. Moclobemide (Aurorix) is a newly developed, effective, short-acting well tolerable and safe antidepressant which belongs to the new class of reversible monoamine-oxidase-A inhibitors. 2. Aurorix was given per os in an open clinical trial for 6 weeks to 30 patients with DSM-III diagnoses of (nonpsychotic, nonmelancholic), major depression. 3. Out of the 25 patients who completed the study 14 (56%) were responders and 11 (44%) non-responders. 4. The patients tolerated the drug very well, and no serious side-effects were noted. 5. Pretreatment biological markers (dexamethasone suppression test, platelet-MAO-B activity, 3H-imipramine binding, thyroid function) did not have a predictive value regarding the drug response. PMID- 8208986 TI - Early life events and panic disorder: course of illness and comorbidity. AB - 1. Some reports have suggested that there may be a link between the experience of traumatic life events in childhood and adolescence and the development of panic disorder in adults. In addition early loss event also seems increase depressive risk by a factor about two to three. 2. The authors wondered whether panic patients who experienced a traumatic life event would have a higher prevalence of subsequent major depressive episode than panic patients without history of depression. 3. One hundred fifty seven patients with panic disorder according DSM III-R criteria are included in this study. Fifty three (33.7%) had experienced a major loss or separation before the age of 15 years. 4. The panic group with early life events showed a significantly higher life time prevalence of major depression than the panic group who did not experience early life events. PMID- 8208987 TI - Additive effect of lithium and clonidine with 5-HT1A agonists in the forced swimming test. AB - 1. The aim of the present work was to demonstrate the possible additive effect of lithium and clonidine with 5-HT1a agonists in the forced swimming test. 2. Anti depressant like effects of 5-HT1a agonists was investigated using forced swimming test. When administered alone, only 8-OH-DPAT reduced the immobility time in mice. 3. 5-HT1a agonists were then tested in combination with clonidine or lithium. Only gepirone and ipsapirone pretreated by either lithium or clonidine reduced immobility time in the forced swimming test. 4. The authors conclude that lithium and clonidine might be useful to predict antidepressant-like activity of new compounds. PMID- 8208988 TI - Long-continuous observation of the effects of methamphetamine on wheel-running and drinking in mice. AB - 1. Effects of methamphetamine (MAP) on wheel-running and drinking in mice, housed under 12-hr light-dark schedule (light period; 06:00-18:00), were investigated through long-continuous observation. 2. MAP (1, 2 and 4 mg/kg, s.c.) acutely increased the wheel-running and drinking for 2-4 hr in a dose-dependent manner after the administration at 11:00, midpoint of light period. 3. MAP administered at 11:00 sub-acutely suppressed the spontaneous increment during dark period (18:00-06:00) in both the behaviors. 4. Many factors, such as the time-of-day and interval of the administration as well as the dose administered, affected the behavioral suppression induced by MAP. 5. In addition to these findings, the wheel-running and drinking during the light period increased even on the days without MAP administration. 6. These results suggest that MAP have not only acute stimulant and sub-acute depressant effects, but also long-lasting effects. PMID- 8208989 TI - The effect of chronic administration of antidepressants and electroconvulsive shock on the 5-HT1A receptor mediated hypothermic response induced by 8-OH-DPAT in the rat. AB - 1. The effect of chronic administration of antidepressants and electroconvulsive shock (ESC) on the hypothermic response (HTR) induced by 8-hydroxy-2-(di-n propyramino) tetralin (8-OH-DPAT) as an index of the function of 5-HT1A receptors was investigated in the rat. 2. 8-OH-DPAT dose-dependently decreased the rectal temperature. 3. Pretreatment with parachlorophenylalanine increased HTR. 4. Chronic administration of the antidepressants, trazodone, imipramine, amitriptyline, and fluoxetine had no effect on HTR, whereas administration of clorgyline attenuated HTR significantly. 5. Repeated ECS had no effect on HTR. 6. These results suggest that the action site of 8-OH-DPAT is post-synaptic 5-HT1A receptors and that the chronic administration of some antidepressants and ECS has no direct action on these receptors. 7. Therefore, the antidepressant effects of these drugs are not produced by direct action on postsynaptic 5-HT1A receptors. PMID- 8208990 TI - [Factors influencing yield shear stress in acute phase of ischemic stroke]. AB - In 36 patients with ischemic stroke the study of factors influencing the yield shear stress, which exemplified the red cells and fibrinogen interaction, was carried out. Patients were divided into two clinical groups: with transient ischemic attack (TIA) and with completed stroke (CS). The frequency of the intensive red cells and fibrinogen interaction was significantly higher in patients the in controls, which may be connected with dysgammaglobulinemia and with an increase of the red cell volume. The lack of significant difference between TIA and CS groups indicated the similar pathomechanism of blood flow changes in cerebral microcirculation in acute phase of TIA as well as of CS. It seems that individual hemorheological changes should be considered first of all in the therapy of this disease. PMID- 8208991 TI - [Results of 5-year activity in a program for pregnant diabetics in south-eastern Poland. I. Methodology of a unified program and evaluation of the degree of diabetes compensation in pregnant women]. AB - A model of diabetic-obstetrical management in pregnant diabetics from the south eastern Poland realized in Cracow has been described. It consists in education, intensive insulin therapy and self-control with borrowed glucose meters. The study included 102 pregnant women enrolled from 1987-1991. It was found that the patients in general with poorly normalized diabetes mellitus referred late to a special unit. It was shown that with experience normoglycemia was achieved with lower insulin doses in four injections. A characteristic feature was a very small number (4) of the patients who had thought of diabetes normalization before pregnancy. Coordinated care provides a possibility of reducing failures in pregnancy, nevertheless it is necessary to develop comprehensive care both before and during pregnancy in diabetic women. PMID- 8208992 TI - [Clinical protocols concerned with disorders of fatty acid beta oxidation]. AB - Inborn defects in fatty acid oxidation are a newly described group of diseases affecting infants and child. This disorder frequently masquerades as Reye's syndrome or sudden infant death syndrome. The known defects, now totaling 11, share many clinical similarities. Clinical manifestations include episodes of coma and hypoglycemia that are induced by fasting, or chronic, progressive muscle weakness and cardiomyopathy. Affected patients are often free of symptoms between episodes. A characteristic organic aciduria or enzyme activity in cultured skin fibroblasts permit diagnosis. Because of high mortality and morbidity rates, early diagnosis is desirable. treatment for survivors siblings is simple and is associated with avoidance of prolonged fasting. Systemic screening of the general population should be initiated to identify those affected and start treatment before they become ill. PMID- 8208993 TI - [Malignant arterial hypertension--clinical picture, prognosis, management]. AB - Malignant hypertension is the most severe form of hypertension. Untreated- quickly leads to target organs damage and death. The most important things are early diagnosis and treatment, which can improve prognosis in the group of patients with malignant hypertension. Pathogenesis of malignant hypertension is not completely established, although histopathological changes are well known. The article presents recent opinions on etiopathogenesis, clinical course and treatment of malignant hypertension. PMID- 8208994 TI - [Atherosclerosis as an inflammatory process. Potential role of adhesion molecules in development of atherosclerosis]. AB - Adherence of monocytes and their subsequent migration into intima appears to be important early event in the formation of foam cell rich atherosclerotic lesion, both in humans and experimental animals. There is increasing evidence that vascular endothelial cells play an active role in these process. In this paper, current knowledge about adhesion molecules presented on the surface of the endothelial cells has been summarized and their role in adhesion and migration or leucocyte both in inflammation and atherosclerosis was characterized. Current concept of pathogenesis of atherosclerosis has been presented, emphasizing the similarities of the mechanism involved to those in inflammation. PMID- 8208995 TI - [Prevention of emesis accompanying antitumor chemotherapy]. PMID- 8208996 TI - [Morphological pictures of renal biopsy specimens in glomerulopathies related to rheumatoid arthritis (RA)]. AB - The authors reevaluated 21 renal biopsy specimens from patients with rheumatoid arthritis (RA) and clinical symptoms of glomerulopathy. The patients were divided into three groups: in the I group they were treated with nonsteroid antiinflammatory drugs, in the II one with gold and in the III group with D penicillamine. Pathomorphological study based on light microscopy, immunohistochemistry and electron microscopy showed that forms of primary renal involvement (group I) and secondary renal involvement (group II and III) in patients with rheumatoid arthritis were very similar to the types of glomerulonephritis not related to RA. The authors pointed out, that in the most cases immunohistochemistry revealed immunoglobulins (IgG,IgA,IgM,C3) and electron microscopy investigations showed deposits in various parts of the glomeruli. This observations support opinions, that immune complex mechanism takes a great role in pathogenesis of glomerulopathy in RA. PMID- 8208997 TI - [Ischemic heart disease in a patient with hypertrophic cardiomyopathy--case report]. PMID- 8208998 TI - [CT investigation of Egyptian mummy from the XXI dynasty period]. AB - The authors presents unique CT scans of an intact egyptian mummy dating back to the 8th c. BC. The CT scans suggest a possibility of preserved papyrus and jewelry from that epoch. PMID- 8208999 TI - [Stefan Zeromski as a patient of St. Lazars Hospital in Cracow]. PMID- 8209000 TI - [Influence of long-term hemodialysis on serum trace elements concentration in patients with chronic renal failure]. AB - 52 patients with chronic renal failure treated by haemodialysis and 21 healthy subjects were observed. All patients were divided into 3 groups: patients treated by 1-50 months haemodialysis (group A), patients treated by 51-100 months haemodialysis (group B), patients treated by 100 months (group C). The blood samples of all patients were withdrawn for the estimation of creatinine, haemoglobin concentration, haematocrit value and zinc, copper, selenium and nickel concentrations immediately before and after dialysis. In healthy subjects only one estimation was provided. In all patients serum zinc, selenium and nickel concentrations were significantly lower than in healthy subjects. Copper concentration was insignificantly higher in normals than in patients with CRF. No significant difference in serum concentration of zinc copper, selenium and nickel between long term (group C) and short term (group A and B) haemodialysis patients was detected. During haemodialysis the decrease of serum zinc, copper and selenium levels was observed in all examined groups. CONCLUSIONS: 1. Serum zinc, selenium and nickel concentrations were significantly lower in patients treated by haemodialysis than in healthy subjects. 2. During haemodialysis the serum concentrations of zinc, copper and selenium were decreased. 3. Serum zinc, copper, selenium and nickel concentrations were the same in long and short term haemodialysed patients. PMID- 8209001 TI - Mortality and cancer incidence following radiotherapy for seminoma of the testis. AB - From the records of the Thames Cancer Registry, 859 patients were identified, who were treated with radiotherapy for seminoma of the testis between 1961 and 1985. Second cancer incidence and mortality and also causes of non-cancer deaths in the study population were examined. Fifty-one (6%) patients died of testicular cancer, 42 within 5 years of diagnosis. There were 42 second cancers (other than second testicular cancers), and 20 deaths from second cancer (expected, 22.1--non significant). The only subtype of cancer with a notable excess was leukaemia (4 incident cases observed; 0.64 expected; relative risk 6.2, 95% C.I., 2.7-14.8, 95% C.I., 2.7-14.7). The overall death rate from causes other than testicular cancer was not elevated (82 observed, 82.06 expected). There was some suggestion of an increase in the risk of mortality with time; for 10 or more years after treatment the relative risk was 1.31 (95% C.I., 0.95-1.81). There was no evidence of excess non-cancer deaths (62 observed, 60 expected). We conclude that there is no definite evidence from this investigation of increased risk of mortality secondary to radiotherapy; however, the excess incidence of leukaemia may be treatment-related and the cohort will be followed further. PMID- 8209002 TI - Present status and perspectives of boron neutron capture therapy. AB - Boron neutron capture therapy (BNCT) is a mode of radiotherapy with great attractiveness, but also with a burden of past failure. In this review, the principles of BNCT, the reasons for its past failure, its present clinical application, and the on-going developmental work towards clinical trials are described. PMID- 8209003 TI - Importance of timing of radiotherapy in breast conserving treatment for early stage breast cancer. AB - This study reports on the treatment results in 508 patients with 514 AJCC stage I II invasive breast carcinomas treated between July 1980 and July 1989. All patients underwent a lumpectomy with axillary lymph node dissection with postoperative irradiation. Adjuvant chemotherapy was given to premenopausal node positive patients. Postmenopausal node-positive patients received adjuvant hormonal treatment. The median follow-up period was 68 months (range, 40-152 months). The 5-year survival rates were 92.6%, 81.4% and 65.5% for stage I, stage IIA and stage IIB, respectively. Distant metastases were the main cause of death. Locoregional failures occurred in 4.9%. Breast recurrences were detected in 17 patients (3.3%). In a Cox proportional hazards analysis, T-stage, pathological margins and interval between surgery and radiotherapy were identified as independent factors predictive of breast recurrence (p < 0.05). The results suggest that radiotherapy should be initiated early after surgery to maintain the breast recurrence rate as low as possible. PMID- 8209005 TI - Continuous split course irradiation for stage I and II Hodgkin's disease: 20 year experience at the Medical College of Wisconsin. AB - Between January 1970 and December 1989, 153 consecutive patients with stage I or II Hodgkin's disease were treated at the Medical College of Wisconsin Affiliated Hospitals. Eighty-eight patients were clinically staged and 65 patients underwent staging laparotomy. Ninety-nine patients were treated using continuous split course irradiation (CSCI) technique. Overall survival (OS) at 5, 10, and 15 years was 89%, 79%, and 68%, respectively. Disease-free survival (DFS) at 5, 10, and 15 years was 75%, 72%, and 68%, respectively. No significant differences were found in OS or DFS when comparing pathologically and clinically staged patients or when comparing patients treated using CSCI with those treated with the standard technique. Patients treated using CSCI tended to complete therapy in a shorter time, without increased morbidity. PMID- 8209004 TI - Quantification of patient to patient variation of skin erythema developing as a response to radiotherapy. AB - A method is described to determine accurately skin redness during a course of radiotherapy using reflectance spectroscopy utilizing information from across the visible spectrum according to the L*a*b* color coordinate system. The method was used to quantify the development of skin erythema during and after electron beam irradiation of the chest wall following mastectomy. A number of factors were identified which could influence the wide variation in response seen between patients. These were: intra- and inter-observer variation; intra- and inter patient variation and variation in the actual dose delivered. Statistical analysis, including an analysis of variance of inter- and intra-patient variation, revealed that the major factor that accounts for the observed difference between patients is a true inter-patient variation, with a coefficient of variation, corrected for intra-patient variation, of 43%. Within the narrow dose range administered in this study, there was no demonstrable dose-effect relationship, raising questions about the role of cell death in the basal layer of the epidermis in the pathogenesis of radiation induced erythema. PMID- 8209006 TI - A re-analysis of available dose-response and time-dose data in Hodgkin's disease. AB - A re-analysis of all available dose-response data on Hodgkin's disease, compiled recently by Vijayakumar and Myrianthopoulos (Vijayakumar, S. and Myrianthopoulos, L.C. An updated dose-response analysis in Hodgkin's disease. Radiother. Oncol. 24: 1-13, 1992), fails to demonstrate any dose-response relationship at doses higher than 32.5 Gy. Thus, in contrast with these authors, we find no evidence that local control will be improved by radiation doses of more than 32.5 Gy. A review of the available data on the time-dose relationship in Hodgkin's disease indicates that overall treatment time, at least up until 7 weeks, is not of major importance. Further, there is some indication that the sensitivity to changes in dose per fraction is low. This allows the fraction size to be selected from considerations of the level of late treatment related morbidity. PMID- 8209007 TI - Maximum and mean bladder dose defined from ultrasonography. Comparison with the ICRU reference in gynaecological brachytherapy. AB - The reference bladder dose for gynaecological intracavitary brachytherapy (BT), as defined by the ICRU 38 Report, is often criticised as it is seldom representative of the highest bladder dose nor it gives an idea of the area exposed to a significant dose. Since November 1990, ultrasound measurements are routinely made in order to determine the actual dose delivered to the bladder of each patient. The technique was as follows. (1) the bladder is filled up with 150 200 cm3 of sterile isotonic saline. (2) The intrauterine position of the tube is checked. (3) The bladder anatomy is controlled. (4) Points of measurements are identified: ICRU bladder reference, minimum distance between bladder mucosa, uterine tube and other similar measurements taken every 15 mm along the radio active line. Maximum and mean doses are calculated at the sagittal plane. Measurements are performed by moving the transducer along the skin of the patient and included in the calculation of dose distribution. Doses delivered to each relevant point are compared. This enables determination to be made of the differences between the ICRU and the doses actually observed at the bladder wall with aid of ultrasonography. BT applications were checked in 58 patients (69 measurements). The method was feasible in all cases. The comparison between ICRU dose from orthogonal films and the ICRU dose from ultrasonography resulted in a 90% accuracy. The maximum and mean doses for utero-vaginal BT are higher than the ICRU dose in 75% of cases (range, 2-8). Measurements are now abandoned for vaginal applications as the ICRU dose only could be measured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209008 TI - Quality assurance in fractionated stereotactic radiotherapy. AB - The recent development of fractionated stereotactic radiotherapy (SRT), which utilises the relocatable Gill-Thomas-Cosman frame (GTC 'repeat localiser'), requires comprehensive quality assurance (QA). This paper focuses on those QA procedures particularly relevant to fractionated SRT treatments, and which have been derived from the technique used at the Royal Marsden Hospital. They primarily relate to the following: (i) GTC frame fitting, initially in the mould room, and then at each imaging session and treatment fraction; (ii) checking of the linear accelerator beam geometry and alignment lasers; and (iii) setting up of the patient for each fraction of treatment. The precision of the fractionated technique therefore depends on monitoring the GTC frame relocation at each fitting, checking the accuracy of the radiation isocentre of the treatment unit, its coincidence with the patient alignment lasers and the adjustments required to set the patient up accurately. The results of our quality control checks show that setting up to a mean radiation isocentre using precisely set-up alignment lasers can be achievable to within 1 mm accuracy. When this is combined with a mean GTC frame relocatability of 1 mm on the patient, a 2-mm allowance between the prescribed isodose surface and the defined target volume is a realistic safety margin for this technique. PMID- 8209009 TI - Dynamics of tumor cell clonogen repopulation in a murine sarcoma treated with cyclophosphamide. AB - Experiments were performed to establish the extent and kinetics of tumor cell repopulation in a murine sarcoma, designated SA-NH, treated with cyclophosphamide (CY). Mice bearing 8-mm leg tumors were treated with 200 mg/kg CY which caused a transient tumor regression. Changes in the absolute clonogen content of tumors was determined by the change in TCD50 values (50% tumor control) obtained under hypoxic conditions of local tumor irradiation at different times after CY treatment until tumors regrew to the pretreatment size. For comparison, hypoxic TCD50 values were determined during the growth of tumors not treated with CY. CY greatly depleted tumors of clonogenic cells as manifested by the reduction in the control TCD50 value of 64.5 Gy to 32.8 Gy 1 day after CY treatment. The reduced TCD50 value remained unchanged for 2 weeks after treatment with CY, at which time the TCD50 began to rapidly increase, continuing until the end of the observation period of 21 days when tumors reached the pretreatment size. In contrast, there was a constant but slower increase in TCD50 values during the growth of tumors not treated with CY. The daily increase in TCD50 was more than twice as high in CY-treated than in CY-untreated tumors: 4.5 Gy/day versus 2.1 Gy/day. This implies that the rate of clonogen production in CY-treated tumors was twice as high as that of unperturbed tumors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209010 TI - Radiobiological determination of growth kinetics and radiosensitivity of pulmonary micrometastases of the R1H tumour. AB - The aim of the study was to determine the radiosensitivity and the growth kinetics of pulmonary micrometastases of the R1H tumour of the rat. Lung metastases were induced by intravenous injection of viable tumour cells. At different time intervals (3-32 days) after injection, lungs were locally irradiated with 200 kVp X-rays, using 1.5 Gy/fraction. Total doses of 6-33 Gy were administered within 11 days. Endpoints used were survival time, local control rate, and number of metastases in the lungs at autopsy. The data were evaluated using the multi-target model. Beginning in the fifth week after tumour cell inoculation the animals started to exhibit a pronounced dyspnoea and were sacrificed. Sections revealed an extensive metastatic infiltration of the lungs. With increasing total dose a prolongation of survival time as well as an increase in cure rate was observed. The number of metastases found in the lungs decreased with increasing total dose. It is concluded that metastatic growth does not start earlier than 3 days after tumour cell inoculation and accelerates continuously. The doubling time of the tumour cells in the micrometastases decreases continuously and from 5.2 to 1.2 days between day 3 and 40, whereas larger metastases containing more than 10(6) cells show gompertzian growth kinetics. The cell doubling time in this stage of metastatic growth is longer than 5 days. During the first 4 weeks of metastatic growth the radiosensitivity of metastatic R1H cells in the lungs is the same as in vitro. PMID- 8209011 TI - Skin-sparing reduction effects of thermoplastics used for patient immobilization in head and neck radiotherapy. AB - Skin-sparing benefits derived from the use of megavoltage photon beams can be strongly reduced when filters are inserted between the source and the patient. The use of plastic masks for immobilizing the patient is the most important cause of this reduction in head and neck treatments. The influence of thermoplastics, commercially available for patient immobilization systems (Orfit Raycast (Luxilon Ind. Co.), Posicast (Sinmed bv) and Optimold (WFR Aquaplast Corp.)), on the patient skin dose value has been investigated by using an NE2534 'Markus' chamber. Indicative measurements with moulded masks (carried out with 2-mm Orfit and 3.2-mm Optimold layers) show significant differences between masks moulded with the two thermoplastics. PMID- 8209012 TI - Soft tissue sarcoma of the breast after conservative surgery and irradiation for early mammary cancer. AB - At Istituto Tumori of Milano in a series of 3295 patients treated with conservative surgery and radiotherapy for breast cancer from 1973 to 1989 three cases of soft tissue sarcoma were observed in irradiated breasts. One patient developed a fibrosarcoma of the breast stroma, 16 months after irradiation. A grade II bulky angiosarcoma was diagnosed in the breast of a patient treated 59 months previously. The third was a grade II angiosarcoma detected 41 months after therapy. At present, the risk of a second primary in the irradiated breast seems too low to justify modification of our present policy of conservative therapy of breast cancer, but a careful and longer follow-up is needed. PMID- 8209013 TI - Saccharide-based contrast agents. Characteristics and diagnostic potential. AB - Since about 1980 tiny bubbles of gas ("microbubbles") have been known to be highly effective in ultrasonography because of enhancing backscatter ultrasound. After about 25 years of experimental work, the first industrial US contrast agent was approved by health authorities, the galactose microparticle SH U 454 Echovist, Schering AG, launched on the German market in 1991. Its major limitation is represented by the fact that it does not pass the pulmonary barrier and is confined to right heart abnormalities. Therefore another agent has been developed, the transpulmonary derivative of Echovist the galactose-based agent with the code number SH U 508 A (Levovist) which is in the late phase of clinical development for cardiac B-mode and Doppler blood pool US enhancement. A wide number of application areas can be foreseen for this contrast agent, which has been used for a multicenter trial. More than 1,200 patients were included in a European phase-III multicenter trial aimed at assessing the diagnostic efficacy and safety of SH U 508 A (Levovist). The patients included in the study had diagnostically insufficient Doppler signal intensity at routine Doppler or color Doppler vascular imaging. In more than 95% of the patients Doppler signal enhancement was achieved with at least one dose at the scheduled regimen, even in peripheral vessels. Enhanced Doppler US allowed a diagnosis to be made in many patients who would have otherwise undergone more invasive procedures. The diagnostic confidence, evaluated on a numerical rating scale (0-100) increased from 25.2 +/- 22.8% (prevalue) to 77.7 +/- 22.2% after Levovist (mean value +/- standard deviation, as calculated for a subgroup of 513 patients). Repeated i.v. injections were well tolerated. No specific risk was found for patients in any disease group. PMID- 8209014 TI - Efficacy of SH U 508 A (Levovist) in color Doppler ultrasonography of hepatocellular carcinoma vascularization. AB - To assess the efficacy of a new US contrast agent [SH U 508 A (Levovist), Schering] in evaluating hepatocellular carcinoma (HCC) vascularization, 38 patients with 43 lesions were submitted to color Doppler US before and after i.v. contrast medium administration. Four patients were studied after arterial chemoembolization. The patients had been selected on the basis of suboptimal color Doppler signals on baseline images. Each patient received two to four injections of Levovist in standard doses. Tumor vascularization was qualitatively graded on a 0-3 scale. Twelve tumors (27.9%) appeared avascular at baseline examinations, while 31 (72.1%) exhibited low to moderate flow signals. After contrast agent administration, color Doppler signals were markedly enhanced in 35/43 lesions (81.4%), lasting 40 to 240 seconds. The lack of enhancement was related to tumor hypovascularity (necrosis at CT), portal vein thrombosis, deep location and successful chemoembolization. The detection of flow signals in chemoembolized tumors was explained by the persistence of viable tumor tissue. After Levovist administration, flow signals were detectable in 97.6% of the HCCs. Therefore, Levovist proved to be an effective tool for color Doppler evaluation of HCC vascularization. PMID- 8209015 TI - Efficacy SH U 508 A (Levovist) as blood pool enhancer in the Doppler evaluation of multiple vascular regions. AB - SH U 508 A (Levovist) as a blood pool enhancer to investigate multiple vascular regions with Doppler ultrasonography. Thirty patients with sub-optimal cardiac or peripheral vascular Doppler exams received 75 intravenous contrast bolus injections in all to investigate the intensity and the duration of Doppler signal enhancement after the i.v. administration of an echo contrast agent - i.e., SH U 508 A (Levovist) by Schering AG, Berlin, Germany. All cases exhibited Doppler enhancement and the investigator's "diagnostic confidence" increased from 35% (precontrast) to 91% (post-contrast) (p < 0.05). Audio Doppler intensity was measured quantitatively and more than 16 dB enhancement was demonstrated in all the vascular regions under investigation (p < 0.05). Enhancement lasted more than 60 seconds in the peripheral vessels and 120 seconds in the heart vessels. No clinically relevant adverse reactions were ever observed. To conclude, i.v., administered SH U 508 A (Levovist) is a valuable means of increasing cardiac, femoral arterial and transcranial (cerebral arterial) Doppler signal intensity. Enhancement is durable and improves the clinical diagnostic confidence in the patients with suboptimal Doppler findings. PMID- 8209016 TI - Color Doppler imaging of liver metastases. The value phase-III of a US contrast agent: SH U 508 A (Levovist) Schering. AB - In a phase-III multicenter clinical trial, the color Doppler vascular patterns were studied of 34 liver metastases in 18 patients before and after the i.v. injection of SH U 508 A (Levovist), with different US units and probes. The patients were selected as having poor color Doppler signals at unenhanced examinations. Lesion size ranged .8 to 9 cm (mean: 3.5 cm). The primary lesion site was the colon in 14 cases, the breast in 8 cases, the lung in 4, the stomach in 4 cases, the ovary in 3 and finally unknown in 4 cases. Each patient received two to four contrast agent injections, with suggested doses and concentrations (10 ml x 300 mg/ml, 8 ml x 400 mgr/ml). No adverse reactions were observed. Thirteen of 34 lesions exhibited no vascular signals at baseline examinations, 10 exhibited some perilesional color spots or small vessel branches, 5 some internal color spots or vessels and 4 small internal and peripheral vessels. After contrast agent infusion, the vascular patterns were better demonstrated in 28/34 lesions and the signal-to-noise ratio was markedly improved, in a concentration dependent manner, from 40 to 240s. Five lesions remained avascular, 11 exhibited "basket"-like vascular patterns, 10 "internal flow" patterns and finally 10 lesions exhibited both. No major correlation was observed between vascular pattern and lesion size. To conclude, the use of the intravenous contrast agent SH U 508 A (Levovist) appears to be a promising technique to improve the color Doppler demonstration of focal metastatic liver lesions. Nonetheless, further studies on larger series of cases are needed to differentiate the different primary sites of the metastases. PMID- 8209017 TI - Color Doppler ultrasonography in the differential diagnosis of focal hepatic lesions. The SH U 508 A (Levovist) experience. AB - The differential diagnosis of focal hepatic lesions is a current problem even though many study methods are available. Color Doppler US has been recently suggested as a diagnostic technique capable of depicting lesion vascularization patterns to better understand lesion nature. However, this examination is often difficult and long. In this study, we investigated the role of a US contrast agent SH U 508 A (Levovist) enhancing the color Doppler signals for easier and better depiction of lesion vascularization. Seventy-four patients with one or more focal hepatic lesions (mean diameter: 5.6 cm) were examined. The lesions were 38 HCCs, 4 cholangiocarcinomas, 1 intrahepatic biliary duct carcinoma, 1 case of multiple adenomas, 2 regenerations nodules in cirrhosis, 2 cases of FNH, 18 metastases and 8 hemangiomas. In 54 cases the US contrast agent allowed the visualization of some vessels inside the lesions which had been missed at baseline examinations. Moreover, the vessels which had been depicted on baseline images were better demonstrated. In all but one patient with severe hepatic steatosis, normal parenchymal vessels were markedly enhanced. Our results in the different kinds of tumors are here reported. PMID- 8209018 TI - Color Doppler flow imaging of renal disease. Value of a new intravenous contrast agent: SH U 508 A (Levovist). AB - This study was aimed at assessing the diagnostic value of a new intravenous contrast agent SH U 508 A (Levovist) in improving color Doppler detection of renal mass vascularity. The study included 30 patients with renal masses: 22 adenocarcinomas, 1 sarcoma, 1 leiomyosarcoma, 1 urothelioma, 1 hemorrhagic cyst and 4 angiomyolipomas. The vascularization of the renal masses was investigated by means of color Doppler US, before and after the intravenous injection of SH U 508 A (Levovist), on the basis of blood flow patterns within and around the lesions. At precontrast scanning, low color Doppler signal at the periphery or within the lesions was observed in 13/30 patients only. After contrast administration, the signal-to-noise ratio increased, which allowed the visualization of tumor vessels in 26/30 patients. In 4/30 patients only no major enhancement of tumor vessels was observed. Our experience suggests that SH U 508 A (Levovist) improves color Doppler sensitivity in depicting the tumor vessels which were missed at baseline exams and in evaluating renal vein and inferior vena cava involvement. PMID- 8209019 TI - The Italian experience with SH U 508 A (Levovist) in breast disease. AB - The authors report their experience with color Doppler US of breast disease with a new parenteral contrast agent--i.e., SH U 508 A (Levovist)--in an international multicenter experimental trial. Over a 9-month period, 17 patients with 19 solid breast lesions were examined. A baseline color Doppler study was performed on every patient, together with a second exam after injecting the contrast agent into a peripheral vein to investigate possible changes in the depiction of tumor vessels, inside and around the lesions. The 19 nodules included 16 infiltrating ductal carcinomas, 2 fibroadenomas and 1 benign phylloid tumor. Levovist improved the depiction of tumor vessels in all cases and helped detect new vascular signals which had been missed on baseline images. The increase in color Doppler signal was graded as marked and mild: in 68.75% of ductal carcinomas and in the benign phylloid tumor signal increase was marked, while in 31.25% of carcinomas and in fibroadenomas signal increase was mild. All lesions exhibited vascular signals both inside and around the lesion; many afferent poles were also depicted. Our results demonstrate that conventional color Doppler semiology changes with the use of a contrast agent and pave the way for further studies on larger series of cases to assess new diagnostic criteria to differentiate breast lesions according to color Doppler signal patterns. PMID- 8209020 TI - US contrast enhancement with intra-arterial CO2 injection in the staging of hepatocellular carcinomas. AB - Liver US contrast enhancement was obtained with the intrahepatic arterial injection of CO2 in 45 hepatocellular carcinoma patients. Before digital subtraction angiography (DSA) all the patients underwent conventional US and CT of the liver; 20 patients also underwent CT during arterial portography (CTAP). Liver US contrast enhancement with CO2 exhibited the same sensitivity as DSA (92%) in demonstrating hypervascular HCCs and proved superior to the other diagnostic procedures -- 85% for CT and 78% for conventional US. DSA combined with echocarbography, with its 2D demonstration of liver anatomy, improved the correct staging of HCCs, for better treatment planning. PMID- 8209021 TI - Ultrasound contrast agents in radiological diagnosis. AB - Contrast enhancement is widely applied to vascular imaging and has become a routine part of diagnostic X-ray, CT, MR and radionuclide methods for vascular diagnosis. Colour Doppler imaging, although offering a unique method for non invasive vascular imaging, suffers limitations determined by the low velocity of blood in small vessels and the weakness of backscattered ultrasound from blood deep in the body. While the low velocity of blood in small vessels remains a fundamental obstacle, there is clear clinical potential for a method capable of enhancing the acoustic backscatter from blood itself, especially in the systemic arterial system, by means of an ultrasound contrast agent. In this paper, studies are made on a stabilized microbubble contrast agent capable of undergoing resonant oscillation in the ultrasound field used to create an image. The effect on this resonant behaviour is that very small quantities of the contrast agent in the systemic arterial circulation can produce outstanding enhancement of Doppler ultrasound signals from major and peripheral arteries. In addition, nonlinear oscillation of these bubbles makes possible an entirely new form of imaging, referred to here as harmonic imaging. It is felt that the use of these contrast agents will enable detection of smaller vessels in the arterial and venous circulation than is currently possible, of neovascular flow associated with malignant tumours, wound healing and possibly the measurement of blood flow rates in such tissues as the myocardium. Harmonic imaging adds to this capability by effectively subtracting Doppler signals from moving solid tissue, thus lowering the threshold of detectable velocity in the vascular system. PMID- 8209022 TI - [Neuroradiology of infective diseases in the immunocompromised host]. AB - Just like the lung, the brain and the spinal cord are target organs for opportunistic infections and tumors in immunocompromised patients. HIV infections and AIDS-related conditions represent the most common cause of immunodeficiency: other causes are hemoproliferative disorders and organ transplantation, but especially long-term drug and radiation therapies. Neurologic (focal, diffuse, meningeal or spinal) signs are the results of CNS infections and/or tumors or of treatment complications. Neuroimaging techniques (MRI better than CT) allow the infective or neoplastic causes of neurologic complications to be nearly always recognized and are therefore major tools for diagnosis and treatment. Lesions characterization is more difficult, since CT and MR patterns are definitely more affected by the evolutive phases of the lesions (encephalitis, cerebritis, abscess) and by their sites than by specific infective agents. However, the knowledge of the statistical possibility of brain and spine infections according to the type of immunocompromission is useful in many cases. PMID- 8209023 TI - [Nuclear imaging in AIDS-related neurologic diseases]. AB - A total of 356 patients with HIV-1 infection at different immunological and neurologic stages were included in this study. Patients with CNS opportunistic signs were excluded. All patients underwent SPET with HMPAO-99mTc; 166 patients were submitted to brain CT and 48 to MRI no later than 30 days after SPET examination. A control group of 12 intravenous drug users with no HIV infection was also examined. In the control group all SPET exams were negative; more positive SPET exams were observed with the progression of clinical and neurologic disease. No correlation was found between SPET positivity and immunological stage. In the asymptomatic stage 54% of SPET findings were positive. SPET was more sensitive than both CT and MRI in defining the abnormal changes of the earlier stages of this syndrome. Since opportunistic infections and neoplasms were excluded from this study and a control group was also considered, our results may indicate a major activity of HIV in the brain and suggest the need to monitor the earlier stages of this disease as well. PMID- 8209024 TI - [Lung infections in acquired immunodeficiency. Clinico-radiologic correlations]. AB - Over the last decade the number of subjects with acquired immunodeficiencies has markedly increased; this phenomenon depends on both the large number of patients receiving organ transplants or antiblastic therapy and the spread of infections caused by the HIV virus. In 70-90% of these patients primary diseases include different pulmonary infections, relative to the type and degree of immune compromission. Pathogenic or, in most cases, opportunistic germs are responsible for severe pneumonia whose mortality rate can top 50%. Since prognosis depends on the promptness of treatment, the diagnosis of nature must be made quickly by integrating clinical and diagnostic findings with laboratory and instrumental results. Conventional chest radiology plays a major role as the first step in a diagnostic iter which can now include rather sensitive techniques--e.g., equalized chest films. CT and nuclear medicine often represent the necessary diagnostic complements but, in some cases, etiology can be diagnosed only with such invasive procedures as lung biopsy. The authors reviewed the current data on the diagnostic imaging findings of pulmonary infections caused by common germs, by Pneumocystis carinii mycobacteria, mycetes and viruses in immunocompromised patients, integrating their personal experience with literature data. PMID- 8209025 TI - [Abdominal manifestations in immunocompromised patients]. AB - Abdominal infections or tumors in the immunocompromised host are both common in AIDS but uncommon in transplant recipients. The role of diagnostic imaging modalities differs in the patients with specific symptoms such as dysphagia, diarrhea, malabsorption and jaundice and in the patients with aspecific clinical findings such as fever, weight loss, superficial lymphadenopathies and abdominal pain. In the former patients, the symptoms suggest a disease of one or more alimentary tracts, in which case radiology is ancillary to clinics and endoscopy plays the leading role to make the diagnosis. However, X-ray barium studies yield valuable information on different types of infections--e.g., Candida, Cytomegalovirus, mycobacterium avium intracellulare and Cryptococcus infections- in Kaposi's sarcoma and in gastrointestinal lymphoma. In these cases CT findings may suggest the diagnosis. In the patients with aspecific findings, US, as an easy immediate examination, and CT, as a panoramic means, can demonstrate deep lymphadenopathies and focal parenchymal lesions which are sometimes suspected to be abscesses or tumors. Moreover, both methods can provide indications and guide to percutaneous needle biopsies. Especially CT findings can distinguish mycobacterial infections from neoplastic lesions on the basis of the involved anatomical sites and of densitometric features. US and CT are useful means to monitor HIV+ subjects, to manage AIDS patients and to follow-up transplant recipients. PMID- 8209026 TI - [Diagnostic imaging in immunosuppressed subjects: malignant tumors]. AB - Each state of immunodeficiency is complicated by an increased incidence of certain types of cancer. The risk factors in the development of malignancies increase in a time-dependent relationship with the age of the defect in cell mediated immunity and some tumors will develop at fairly distinct time intervals during immunodeficiency. Thus, Kaposi's sarcoma appears mostly when the degree of immunodeficiency is slight (average time: 23 months), non-Hodgkin's lymphoma is prevalent in an intermediate phase (average time: 37 months) and some carcinomas will appear only if immunodeficiency lasts many years. Many hypotheses have been suggested as to the biological mechanisms by which an immunity defect contributes to the development of malignancies: the most credible of them is the one suggesting the action of some oncogenic viruses which are not sufficiently controlled by the immune system. Kaposi's sarcomas and non-Hodgkin's lymphomas are the most common types of tumor in AIDS patients. Other tumors--except for Hodgkin's lymphoma--are seldom reported in HIV patients. However, the incidence of carcinomas is thought to be likely to increase in the next few years, because the longer survival of HIV patients, without strengthening their immune system, will unfortunately allow the tumors with longer onset time to develop. As for Kaposi's sarcomas and non-Hodgkin's lymphomas, the major epidemiological data are reported, together with some etiopathogenetic hypotheses and the main clinical and radiologic patterns. Other solid tumors in HIV patients and their clinical and radiologic features are reported too. Our series of cases was collected by the GICAT (Italian Cooperative Group on AIDS-related Tumors) which coordinates epidemiological studies, supports medical research and standardizes the treatment of patients suffering from HIV-related tumors. PMID- 8209027 TI - [AIDS in childhood]. AB - HIV infection in infants is transmitted through the placenta. Antibodies reduce and annul in nearly 18 months: HIV + subjects older than 18 months are considered as infected and divided into two classes--i.e., P1: infected and P2: AIDS. The most interesting clinical and diagnostic imaging findings are reported relative to 209 babies who were born HIV + and followed-up with clinical and laboratory tests plus chest films, brain and abdomen US to assess the presence of changes and their evolution features. The following conclusions have been drawn: 1) in their early life, HIV + subjects are especially liable to the action of bacteria, viruses and protozoa: their respiratory system is easily affected with acute, recurring and/or chronic inflammations which are frequently associated with heart enlargement from dilatative cardiomyopathy. Bacterial inflammations are characterized by single or multiple opacities, with blurred and irregular patterns, which are frequently confluent in areas of inhomogeneous opacity. The diagnosis of virus and protozoa infections is more difficult because of their radiologic patterns--i.e., linear fan-like opacities, small shadow areas, enlarged hila. In some cases radiology demonstrates only or mostly lung hyperexpansion, with no opaque images, which however does not exclude the presence of severe and diffuse bronchioloalveolar and interstitial compromission with high-grade pulmonary insufficiency. The common association of cytomegalovirus and Pneumocystis carinii infections with slow-evolution changes and frequent recurrences appears on radiologic images as diffuse and blurred shadows and irregular cotton-like opacities. 2) Brain and abdomen US scans in the newborn show no particular changes, while in the following months both US and CT demonstrate hydrocephalic, atrophic and hemorrhagic changes. 3) In both early and late infancy, lung infections are mostly caused by pneumocystis and cytomegalovirus. Chronic interstitial lymphocyte pneumonia is a peculiar finding with punctiform images in the bases of lung and spreading craniocaudally with similar features to miliary tuberculosis. Different than in the adult, in our series of 209 infants no tubercular abnormalities were observed: in one patient only an active primary complex was demonstrated with broncholavage. Candida infections were observed in 3 patients in their late infancy. Hepatopancreatic and lymph node changes suggesting probably evolving inflammation were uncommon in our series; this condition must be followed-up and checked over time. PMID- 8209028 TI - [Interventional modalities in immunosuppressed patients]. AB - In immunocompromised patients interventional modalities have diagnostic and/or therapeutic purposes--in both cases they are justified on the basis of the frequently aspecific clinical and instrumental findings and because of the clinical need to carry out the most specific treatment as soon as possible. The authors stress the particular weakness of immunocompromised patients to invasive approaches and discuss the indications, contraindications and precautions which must be taken when performing interventional radiologic modalities. Diagnostic imaging uses radioscopy, US and CT for guidance, each of them allowing a rapid percutaneous confirmation of lesion nature, the assessment of infection in a collection, of a neoplastic lesion type, or of the microbiology of an infectious lesion. Interventional modalities are frequently indicated in chest diseases- e.g., for punctures and percutaneous drainage of empyematous pleural collections or of pulmonary abscesses, percutaneous needle biopsies of lung lesions, or endoscopic dilatation of tracheobronchial stenoses. The percutaneous drainage of lung abscesses in immunocompromised patients makes recovery easier. The diagnostic accuracy of the results of needle biopsy is lower in lung infections than in neoplastic lesions. Indications to abdominal interventional procedures are less frequent--i.e., percutaneous drainage of rare abscesses, percutaneous needle biopsy of nodal mesenteric or lumboaortic masses. Some clinical conditions are diagnosed only with invasive radiologic procedures--e.g., ERCP diagnoses sclerosing cholangitis in AIDS. CT is the basic and the best modality to guide percutaneous drainage in both the abdomen and the chest, to assess contraindications or to indicate some specific modes; in some cases even plurifocal abscesses can be treated with a percutaneous imaging approach. PMID- 8209029 TI - [AIDS: organizational and medico-legal problems]. AB - The medical imaging of AIDS patients may turn out a major challenge for hospital organization, since the specific problems related to this syndrome in terms of abnormal changes and increased diagnostic burden are to be matched with infection control procedures. Data obtained from 12 radiology departments in Lombardia hospitals where an Infectious Disease Department is present may yield valuable indications about the optimization of resources and how to implement sound cost benefit measures while taking care of patient needs. Professional exposure to HIV may be substantially reduced by educational and practical measures, whereas strict hygienic standards applied to hospital environment and individual patients are of great value in controlling nosocomial infections in this population of immunodepressed individuals. The growing problem of HIV seropositive health care workers may be positively addressed with a modulated approach combining the contrasting issues of patients safety and non-discriminating job policy. PMID- 8209030 TI - [Morphological study of ovum and nymphs of Dipetalogaster maximus (Uhler, 1894) (Hemiptera, Reduviidae, Triatominae)]. AB - Intending to provide new parameters to be used in Triatomines' Taxonomy, vectors of Chaga's Disease and to amplify a large range of knowledge about this species, a study of the structure of the egg and external morphology of the five nymphal instars was done. The eggs show under optical microscope (M.O.), the chorium's surface of the body and the operculum formed by poligonal areas, clearer under scanning electronic microscope (MEV). The apex of the third rostrum segment in all 5 instars nymphs, show 1 + 1 invaginated and elongated structures and the apical portion of the second tarsal segment presents a group of more or less numerous, very long, delicated and golden hairs. PMID- 8209031 TI - [Experimental study of fecal excretion of nitrogen in different nutritional conditions]. AB - Fecal nitrogen excretion in different nutritional conditions were studied in 32 adult Wistar rats, casually distributed in four groups: group A (12), with normal control rats; group B (6), with subcutaneous impalnt of Walker-256 carcinosarcoma, at the beginning of the experiment; group C (8), with tumor implant eight days before the experiment beginning; group D (6), with standard skin wound in 15th day. The animals were fed with normoproteic diet (25% casein content). Nitrogen ingestion and urinary and fecal excretion were daily measured. Evaluation selected parameters were: nitrogen ingestion and urinary, fecal and total excretion; nitrogen fecal excretion/ingestion, nitrogen fecal excretion/urinary excretion and nitrogen fecal excretion/total excretion ratios; nitrogen urinary excretion/ingestion and nitrogen urinary excretion/total excretion ratios. Adequate statistical analysis was done with p < 0.05 critical limit value. It was observed that in normal animals nitrogen fecal excretion was equal to 5.7% ingestion value, 12.0% urinary excretion and 10.8% total excretion. In presence of malignant tumor, nitrogen fecal excretion was equal to 79% of normal animals value. In rats with skin wound in cicatrization nitrogen fecal excretion was 70.5% of normal animals value. PMID- 8209032 TI - [Ultrastructure of the boundary tissue of the extratesticular rete and efferent ductules in the cat (Felis domestica, L.)]. AB - In the cat the boundary tissue of the extratesticular rete testis and efferent ductules is formed by lamellar and fibrillar collagen and elongated contractile cells. These cells are mainly represented by smooth muscle cells and myofibroblasts. PMID- 8209033 TI - [Ultrastructural characteristics of Sertoli cells of the vampire bat (Desmodus rotundus rotundus, Geoffrey, 1810)]. AB - This paper deals with the ultrastructural study of mature vampire bat Sertoli cells and their relationships with the different stages of testicular germ cells. In vampire bat seminiferous epithelium there are different types of junctional specializations among Sertoli cells and among Sertoli cells and different germ cells, with special emphasis to tight junctions and to junctions like as desmosomes. Ectoplasmic junctions through the Sertoli cells, including the smooth ER, are observed. These cellular interactions and their cytophysiological roles are discussed. Also are related some ultrastructural peculiarities of the Sertoli cell nucleus, nucleolus, cytoplasmic organelles and lipidic inclusions. PMID- 8209034 TI - [Ultrastructural morphometric study of sex dimorphism in cells of the ductus granulosus of the submandibular glands of mice]. AB - The sexual dimorphism in the secretory cell of the granular convolated tubule of mouse submandibular gland was morphometrically studied in light and electronic microscope level. In semithin sections (0.5 micron) the nuclear volume (Bach, 1963) and the fractions of cellular volume occupied by the nucleus and by cytoplasm were determined (Chalkley, 1943). In twenty electronmicrographs per animal with a final magnification of x 15.000, using the Weibel's et al. (1966) multiproposition test system, were obtained relatives morphometrics data, which multiplied by the cytoplasmatic volume provided us the respective absolute values. The results showed a presence of a sexual dimorphism at subcellular level. The secretory cell of the male is higher and exhibit a greater volume when compared with that cells of the female. In the male that cells are characterized by a higher total volume of the endoplasmic reticulum, Golgi complex and secretory granules. The secretory granules and the condensation vacuoles size are more developed in male cells. The female secretory granular cells exhibit a greater absolute number of the condensation vacuoles and secretory granules, as well as, a higher mitochondria total volume and surface. PMID- 8209035 TI - [Helminth parasites of capybaras (Hydrochaeris hydrochaeris) on sub-region of Nhecolandia, Pantanal, Mato Grosso do Sul]. AB - A sequence of 23 necropsies was carried out on capybaras (Hydrochaeris hydrochaeris) from the central area of Nhecolandia, Pantanal region, state of Mato Grosso do Sul, Brazil, from December 1984 to December 1986. The helminths identified and their respective prevalences and mean intensity were: Trichostrongylus axei--60.9 and 14, Viannella hydrochoeri--95.6 and 1031, Strongyloides chapini--47.8 and 1014, Yatesia hydrochoerus--44.4 and 6, Cruorifilaria tuberocauda--40.0 and 8, Capillaria hydrochoeri--86.9 and 156, Protozoophaga obesa--100.0 and 7212, Taxorchis schistocotyle--56.5 and 43, Hippocrepis hippocrepis--34.8 and 3832, Nudacotyle tertius--8.7 and 133, Monoecocestus hydrochoeri--54.5 and 62, and Monoecocestus hagmanni--80.0 and 75. Y. hydrochoerus was registered for the first time in Brazil. The helminths C. tuberocauda, V. hydrochoeri, S. chapini and H. hippocrepis has characteristics that induce clinical and subclinical parasitosis. Although multiple infections predominated, no interactions among the helminth parasites of the same organ were observed. The prevalences and abundances of S. chapini, Y. hydrochoerus and C. hydrochoeri were influenced by the age of the host. So, S. chapini presented higher values in young animals, while Y. hydrochoerus and C. hydrochoeri showed an opposite tendency. PMID- 8209036 TI - [Clinical and microbiological study of acute pelvic inflammatory disease]. AB - Upper genital tract infection was investigated in 46 women admitted to hospital with clinic diagnosis of acute pelvic inflammatory disease (PID) and 62 control women accepted to hospital for laparoscopy Fallopian tubes sterilization. Diagnosis was ratified by laparoscopy in mild and moderate salpingitis; culdocentesis and ultrasonography were performed in severe salpingitis and endometrial sample was made in endometritis. Microbiological specimens were taken from the cervix and abdomen. Antecedents and complete clinical studies were obtained. Patients were treated with antibiotic association sodic G penicillin, chloramphenicol and gentamicin. Risk factors to development PID were: single female (p < 0.05), multiple sexual partner (p < 0.01), previous PID (p < 0.05), infertility (p < 0.05), mean year of IUD use in severe salpingitis (p = 0.05) and mean years of age from women with sexually transmitted bacterias (STB) vs endogenous bacterias (EB) (p < 0.05). In the control group no abdomen bacterias were isolated. In patients with PID, C. trachomatis was detected by serology in 28.3%. N. gonorrhoeae was isolated from the cervix in 23.9% and from the abdomen 17.4%. Besides it was isolated from the abdomen: M. hominis 17.3% and E. coli 15.2%. STB were isolated in 54.3% and EB in 47.8% of the patients. Bacterial association was present on the 37%. Cervix isolation of G. vaginalis and Mycoplasma were not correlated with development of PID. Cervix microbiological samples were useful to know abdomen microbic etiology. They coincide with those in the 90.9%. EB were more frequently isolated from severe salpingitis (p = 0.05) and STB from mild and moderate salpingitis (p = 0.05). Antibiotic association cured all the mild and moderate salpingitis with independence of bacterial etiology. Failure occurred in 2 diffuse peritonitis and 13/14 tubo-ovarian abscesses. Surgery used in severe salpingitis and diffuse peritonitis, principally consisted in anexectomy, peritoneal toilet and drainages. No hysterectomies were performed. Colpotomy drainage was used as a laparotomy complement or as unique drainage. Severe complications of surgery occurred in 10.5%. Failure in antibiotic treatment, surgery and complications were present with preference in PID with EB. After PID 26.5% of women had both Fallopian tubes damaged; in 39.7% tube damage was not evaluated and in 34.2% one tube rested in health. Damage did not depend of bacterial etiology. Conclusion on the necessity of adequate prevention of this disease and it should need education related to the roll of STB and standards about the IUD use. PMID- 8209037 TI - [Practicability of panoramic hysteroscopy with CO2. Clinical experience: 923 cases]. AB - Between 1987 and 1990, Diagnostic Panoramic Hysteroscopies with CO2 as distending medium was proposed in 890 cases. Age groups, complications and failures are discussed. The notion of "insufficient" hysteroscopy is defined as well as the attitude toward this situation. A technique, vaginoscopy is described, making possible to perform the examination in patients that never had sexual intercourse or senile patients. Vaginoscopy and repetitive hysteroscopy after the first hysteroscopy found insufficient are important tools to achieve good diagnosis and fewer than 1% failure of the procedure among patients with narrow introitus. PMID- 8209039 TI - [Translaparoscopic surgical experience in the Dr. Gustavo Fricke Hospital]. AB - The experience of 160 translaparoscopic surgical patients with gynecological pathologic is described. The advantages and disadvantages of this technique are discussed as well as the future developments which indicate that it will replace the classical surgery by laparotomy. PMID- 8209038 TI - [Ligation of internal iliac artery as treatment of hemorrhage in obstetrics and gynecology]. AB - Twenty five cases of severe or persistent bleeding in obstetric and gynecologic patients treated with internal iliac arterial ligation are analyzed. A short history of every patient is described. There was no complication of the procedure neither ischemia after several years of control. Four pregnancies in two cases observed in seven years. The procedure failed in three cases, but was successful in the others. It is concluded that the coagulopathy when it is present must be corrected and the internal iliac arterial ligation is certainly it is a useful alternative as extreme solution in some cases of severe or persistent hemorrhage. PMID- 8209040 TI - [Acute fatty liver of pregnancy: 2 clinical cases]. AB - The clinical evolution and the laboratory pattern of two patients with histopathologically confirmed fatty liver of pregnancy is described. Both babies were delivered vaginally after oxytocic induction and the mothers recovered completely during the puerperium. There was one fetal death in labor secondary to severe abdominal vascular malformation. The other fetus was born healthy. PMID- 8209041 TI - [Depressive disorders during pregnancy and associated factors]. AB - A group of 125 pregnant women is studied that is under the control of 2 urban and 1 rural health clinic, were it was found an incidence of 29% of depressive disorders. It is observed that three aspects are strongly related with this disorders: unwanted pregnancy, unsatisfactory couple relationships and personal back-ground with depression. A working model is proposed that seeks to comprehend this phenomenon in its entirety. PMID- 8209042 TI - [Electrosurgery resection of intraepithelial lesions of lower female genital tract]. AB - Twenty patients bearing lesions caused by human papillomavirus and intraepithelial neoplasia of the lower genital tract and treated with electrosurgical excision of the lesions are presented. The technique used, the benefits of the histopathologic assessment of the specimen, and the changes that this procedure produces in the specimen tissue are analyzed. In general terms, the pre and postoperative diagnosis were concordant and the early and late morbidity was found to be not significative. The efficacy of this therapy in the long term remains to be evaluated. PMID- 8209043 TI - [Massive digestive hemorrhage secondary to typhoid ulcer in pregnancy]. PMID- 8209044 TI - [Usefulness of GnRH agonists in preoperative treatment of complicated uterine myomata]. AB - The use of long acting gonadotropin-releasing hormone (Gn-RH) agonist produces a reversible hypogonadotropic hypogonadism. This effect has been used as presurgical treatment of uterine myomata, resulting in amenorrhea and reduction in uterus and tumour sizes. We describe the case of a 43 year old patient, having a uterine myoma associated with metrorrhagia, admitted to hospital because of extensive deep phlebothrombosis requiring urgent anticoagulation. Because of the risk of exacerbating metrorrhagia and considering the high morbidity associated to emergency hysterectomy, we decided medical treatment with a depot GnRH agonist (leuprolide acetate 3.75 mg IM monthly). Bleeding ceased within 3 days, allowing the maintenance of anticoagulant treatment. A marked reduction in uterine size postponed total hysterectomy to 3 months later. The characteristics of GnRH analogues, their action mechanisms, adverse effects and other clinical indications are discussed. PMID- 8209045 TI - [About wound healing, factors that perturb, infection mechanisms, factors that help, antiseptics and sutures materials (II Part)]. PMID- 8209046 TI - [Metabolic control in patients with pre-pregnancy diabetes and risk of congenital abnormalities]. PMID- 8209047 TI - [Biographic traits of 3 gynecologic illustrious specialists. Doctors Ramon Zegers Perez, Enrique Arancibia Basterrica and Eduardo de Ramon Urzua]. PMID- 8209048 TI - [Gynecologic complications associated with prolonged use of tamoxifen to breast neoplasms]. PMID- 8209049 TI - [Usefulness of transvaginal Doppler color in ovarian neoplasms diagnosis]. AB - The vascular resistant evaluation by Doppler waveform is a method used in clinic and research. The neoplastic malignant has an increased growth with an increased amount of neomalignant vessels. The presence of these vessels produce an increase of the transversal section area from the tumoral vascular system, therefore there is a decrease in the vascular resistance. The main objective of this work is to show the usefulness of Doppler waveform as predictor factor of malignity in ovary tumors. Eighteen patients with tumoral mass in the ovary were studied. They were between 21 and 67 years old (mean = 43). The tumoral volume and the flow resistance of blood vessels which irrigated those tumoral mass were evaluated by transvaginal ultrasound with color and pulsed Doppler. The pulsatility index (SD/media) was used. The Chi cuadrado test was used to evaluate the results. The results show the presence of six malignant tumors, three of them with low malignicity and the presence of twelve benign tumors. The age of the patients between both groups (malignant and benign tumors) were significant different (40.7 versus 52 years old, p < 0.001). The mean tumoral volume was 65 ml, with a range of 17 to 225 ml in the group of patients with benign tumors and the mean tumoral volume from patients with malignant tumors was 951 ml with a range of 141 to 3142 ml. The difference in the tumoral in both groups was significative with p < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209050 TI - Selective decontamination: has the pendulum swung too far? PMID- 8209051 TI - Intravenous antibiotic therapy in cystic fibrosis: in hospital or at home? PMID- 8209052 TI - Exercised-induced asthma revisited. PMID- 8209053 TI - Cytomegalovirus pneumonia--a consequence of immunosuppression and pre-existing lung damage rather than immunopathology? PMID- 8209054 TI - Respiratory muscles in endocrinopathies. AB - The aim of this review was to demonstrate that RM function is altered in various endocrinopathies and that RM weakness is a common finding. RM function has been well-studied in diseases such as thyroid dysfunction, and steroid induced RM myopathies. Less well documented reports on RM function were found in parathyroid dysfunctions, disorders of mineralocorticoids and pituitary disturbances. Controversial reports were found in diabetes mellitus. No report was found connecting RM function with androgens, pheochromocytoma or adrenaline deficiency in humans. These diseases could potentially cause RM impairment leading to severe respiratory failure (pump failure) putting life in great danger. Therefore, it is obvious that further studies are needed to investigate the performance of RMs in endocrinopathies. Such studies are extremely urgent in Cushing's and Addison's disease, acromegaly, disorders of the adrenal medulla, and in diabetes insipidus. PMID- 8209055 TI - Variable response to bronchodilator therapy in young children born prematurely. AB - The response to nebulized therapy was studied at a median postnatal age of 16 months (range 6-24 months) in 15 children born prematurely. Thoracic gas volume (TGV) and airways resistance (RAW) were measured by total body plethysmography and specific conductance (SGAW) calculated. The measurements were made prior to, and then 5 and 10 min after, nebulized saline (3 ml), and then 5, 10 and 15 min after administration of nebulized salbutamol (2.5 mg in 2.5 ml normal saline). There was no significant change in TGV throughout the study period. One child showed a significant improvement in airways resistance following nebulized saline, and no child had a significant deterioration. RAW and SGAW both significantly improved in the group overall at 15 min following salbutamol (P < 0.05, P < 0.03 respectively). Individual patients, however, showed a variable serial response in RAW and SGAW: four children had a paradoxical response (an increase in RAW and a decrease in SGAW) at 5 min and at 10 or 15 min, seven children had a significant improvement (decrease) in RAW and eight a significant improvement (decrease) in SGAW. The children who had an initial paradoxical effect did not differ significantly in either age or baseline lung function from the other infants. Patients in whom RAW and SGAW improved following bronchodilator did not differ in age from the rest of the study group, but had tended to have worse lung function prior to bronchodilator administration. We conclude that there is a variable response to nebulized salbutamol in children born preterm, this treatment should only be administered in association with careful monitoring. PMID- 8209056 TI - Bronchoalveolar lavage and 99mTc-DTPA clearance as prognostic factors in asbestos workers with and without asbestosis. AB - The aims of this study are to investigate the change-over time of lung function and chest radiographic findings in patients with asbestosis (AS) and asbestos workers without asbestosis (AW). Secondly, to correlate these changes with broncho-alveolar lavage (BAL) profiles and with lung epithelial permeability, as detected by half-time lung-to-blood (t1/2 LB) clearance of an inhaled aerosol of diethylene triamine pentacetate labelled with technetium 99 (99mTc-DTPA) obtained a mean period of 4.2 yr (range 2.3-5.8) previously. Thirty-three patients with asbestosis and 24 asbestos workers with substantial asbestos exposure were followed-up. Nineteen healthy smokers (HS) with no asbestos exposure who were followed up for a mean period of 3.9 yr were taken as a control group for spirometric changes. Compared with AW, FEV1, FVC and TLCO were lower in AS (P < 0.0001 in each case). Smoker AS and AW had lower numbers (P < 0.03) and percentages (P < 0.004) of BAL lymphocytes and higher numbers (P < 0.04) and percentages (P < 0.02) of BAL neutrophils plus eosinophils than ex- and non smokers. Annual declines of FEV1 (dFEV1 yr-1) and FVC (dFVC yr-1) in AS and AW were significantly greater than in HS and predicted annual declines (P < 0.002 in each case). Annual declines of TLCO (dTLCO yr-1) and KCO (dKCO yr-1) in AS and AW were significantly greater than predicted annual declines (P < 0.002 in each case). No significant differences were noted between AS and AW in annual declines in any lung function measurement. dTLCO yr-1, dKCO yr-1 were significantly greater in smokers than in ex- and non-smokers, (P < 0.05 and P < 0.04 respectively). Annual decline did not relate to base line values for any lung function measurement. Numbers and proportions of BAL lymphocyte were higher (P < 0.008 and P < 0.02, respectively) and numbers and proportions of BAL neutrophils and eosinophils were lower (P < 0.02 and P < 0.03, respectively) in patients in whom dTLCO yr-1 was less than 0.3 mmol min-1 kPa-1 than in patients in whom dTLCO yr-1 was more than 0.3 mmol min-1 kPa-1. dTLCO yr-1 inversely correlated with t1/2 LB; r = 0.51; (P < 0.008). Patients in whom the radiograph remained unchanged had higher numbers (P < 0.002) and percentages (P < 0.001) of BAL lymphocytes than patients in whom the radiograph deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209057 TI - Bronchodilator response to nebulized salbutamol in elderly patients with stable chronic airflow limitation. AB - The bronchodilator response to 5 mg nebulized salbutamol was studied in 20 elderly patients with stable chronic airflow limitation. Salbutamol produced significantly greater increases in FEV1 and FVC compared with placebo although there was no difference in subjective sensation of breathlessness. Spirometry can be successfully used to assess respiratory function in appropriately selected elderly patients with chronic airflow limitation. PMID- 8209058 TI - Voluntary suppression of cough induced by inhalation of capsaicin in healthy volunteers. AB - The aim of the present study was to investigate the voluntary suppression of cough in response to capsaicin inhalation in healthy volunteers, and to determine if the dose-response curve to capsaicin was significantly altered when volunteers were asked to suppress their cough response. The quantification of the degree of voluntary suppression of induced cough could provide a new methodology for screening antitussive agents as antitussives may act by influencing voluntary control of cough. Cough was induced by inhalation of capsaicin. Two challenges were given 5 min apart, each comprising five ascending concentrations of capsaicin (1 x 10(-5) M-3.33 x 10(-4) M). During one of these challenges the volunteer was allowed to cough when required, and during the other they were asked to suppress cough. These two conditions were given in random order. The cough response was recorded by means of a microphone with the integrated sound trace displayed on a chart recorder. A dose-response relationship was obtained on administration of ascending concentrations of capsaicin. In the non-suppressed challenge 23/24 subjects coughed on inhalation of capsaicin (3.33 x 10(-4) M) with a mean number of coughs of 2.92 +/- 0.34, whereas in the suppressed challenge only 3/24 subjects coughed with a mean number of coughs of 0.29 +/- 0.18 (P < 0.001). These results demonstrate that cough induced by inhalation of capsaicin can be voluntarily suppressed. The mechanism of voluntary suppression of cough is discussed in relation to capsaicin challenge and the screening of antitussive medications. PMID- 8209059 TI - Elevated serum levels of soluble interleukin-2 receptors in lung cancer and the effect of surgery. PMID- 8209060 TI - Nasal intermittent positive pressure ventilation in acute exacerbations of chronic obstructive pulmonary disease--a preliminary study. AB - Ten patients (two male) suffering from acute exacerbations of long-standing chronic obstructive pulmonary disease and admitted in hypoxic, hypercapnic respiratory failure were treated with Nasal Intermittent Positive Pressure Ventilation (NIPPV) plus supplemental oxygen, on a general medical ward. The median (range) pH on admission was 7.30 (7.20-7.35), the median age was 67 years (47-77) with an FEV1 (percent of predicted) of 30 (17-39). On admission the median arterial oxygen tension (PaO2) was 4.71 kPa (3.45-6.26) on air, and the carbon dioxide tension (PaCO2) was 7.68 kPa (6.85-9.83). With controlled oxygen therapy there was no significant improvement in PaO2, but the median PaCO2 increased significantly to 9.75 kPa (7.04-11.70) (P < 0.05). By using NIPPV with supplemental oxygen it was possible to significantly improve the median PaO2 to 11.25 kPa (6.70-26.90) (P < 0.01) without worsening PaCO2 levels (8.96 kPa; 6.85 13.10). NIPPV was applied by a senior, respiratory physiotherapist and used intermittently depending on patient tolerance and clinical response. The median total time on NIPPV was 27 h, delivered over 1-5 days. One patient found the mask difficult to tolerate beyond a short period of time. NIPPV was well accepted on a general ward by nursing staff. Three patients later died with progressive hypercapnia, despite an initial response; with one of these patients also receiving intubation and mechanical ventilation. A further patient also received intubation and mechanical ventilation and was eventually discharged. NIPPV plus supplemental oxygen offers a method to correct hypoxaemia on a general medical ward without worsening hypercapnia for acute on chronic, hypoxic, hypercapnic respiratory failure, and warrants further investigation. PMID- 8209061 TI - A comparison of spirometric variables in cystic fibrosis and bronchiectasis over 4 years. PMID- 8209062 TI - Successful fibrin glue repair of iatrogenic bronchial rupture. PMID- 8209063 TI - Chemoprophylaxis for tuberculosis. PMID- 8209064 TI - Spontaneous intrapleural rupture of mediastinal teratoma--Ashour M, Hawass el Din, Adam KAR, Joharjy I. Respir Med 1993; 87: 69-72. PMID- 8209065 TI - Pneumothorax in patients with AIDS. PMID- 8209066 TI - Antibiotic prescribing for bronchitis: time for a change? PMID- 8209067 TI - Guidelines for the measurement of respiratory function. Recommendations of the British Thoracic Society and the Association of Respiratory Technicians and Physiologists. PMID- 8209068 TI - Asthma deaths among coloured and white South Africans: 1962 to 1988. AB - To determine whether death rates from asthma have been rising in South Africa, asthma mortality rates among coloured and white South Africans were calculated from official figures for the years 1962-1988. Sharp increases in the 1960s were noted in both groups. Since the early 1970s whites rates have generally shown a downward trend. In contrast, coloured rates have remained high, with a marked excess of male deaths. In the age stratum 5-34 years, there has been considerable fluctuation, with the long-term trend being slightly downward. Some increase in death rates occurred among the young in the early 1980s, but coloureds in this age group have shown falling rates in the most recent years. Coloured death rates in the younger age stratum have, however, continued to exceed whites rates, although by a decreasing margin, and have been high by international comparison. These group disparities are unlikely to be due to differences in certification or in coding. Variation in prevalence or severity of asthma may explain some of the disparity. However, these group differences, taken with well-known inequalities in medical care, suggest that preventable determinants of asthma deaths related to access to and quality of medical care may be important and accordingly a target for preventive strategies. PMID- 8209069 TI - The quantitative distribution of nebulized antibiotic in the lung in cystic fibrosis. AB - Nebulized antibiotic therapy in cystic fibrosis is an established procedure. The present study was designed to quantitate deposition, and assess its relation to the disease state. Twenty seven children and young adults with cystic fibrosis (mean 11.6 years, range 4-23 years, 12 females) were studied to establish the quantity and pattern of deposition of nebulized tobramycin in the respiratory tract. A single (120 mg) dose of nebulized 99 m technetium-labelled tobramycin was administered, and imaged with a gamma-camera. The mean penetration index (which compares the distribution of 81 m-Krypton gas with Tc-radioaerosol) was also used to measure peripheral deposition efficiency. The aerosol mass median diameter (MMAD) for the compressor-nebulizer system used was 5.3 u, measured with the Malvern Mastersizer. Serial sputum samples were fluroimmunoassayed for tobramycin in nine patients. A mean of 8.0 (SEM 1.0) mg tobramycin reached the lungs. There was no relationship between the total pulmonary deposition and indices of pulmonary damage in cystic fibrosis. Sixteen percent of the lung tobramycin reached the periphery. The greater the lung damage as indicated by FEV1 and Chrispin-Norman scores, the smaller the proportion of pulmonary tobramycin that reached the periphery. The mean penetration index increased with increase in the FRC, but bore no relation to other respiratory function tests or to chest X-ray scores. Sputum tobramycin concentrations reached levels bactericidal for Pseudomonas aeruginosa. Airway obstruction and damage affected the proportion of pulmonary tobramycin reaching the periphery. The proportion of tobramycin reaching the lungs was small and variable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209070 TI - Tuberculosis case-finding in Western Australia. AB - The records of a total of 497 patients notified to have active tuberculosis (TB) in Western Australia from 1986 to 1990 inclusive have been reviewed in relation to case-finding. Of these, 276 (55.5%) were Asian migrants, 92 (18.5%) Europeans and 110 (22.1%) Australians. The disease was confirmed bacteriologically in 247 (49.7%). The most common mode of diagnosis was symptomatic presentation (39.8%), followed by migrant health surveillance (36.8%), incidental finding (7.5%), regular follow-up (3.8%) and pre-employment chest radiography (1.8%). Contact examination in the non-Asians accounted for only 0.4% while diagnosis after death 2.6%. There was no statistical difference in the detection of TB disease and infection among contacts of index patients with diseases at different sites or of different bacteriological status. The results of the study justify the present strict surveillance over the Asian migrants but do not support the overcautious policy of the contact examination procedures in the non-Asians, for which changes are proposed. Twelve patients whose confirmed TB was diagnosed only at autopsy had a mean age of 75.4 (range 41-86) years. Six of them had miliary or disseminated TB, three co-existing serious medical conditions and none a past history of the disease. The pattern has been well described and clinicians should keep a high index of suspicion for TB in this group of patients. PMID- 8209071 TI - Peak expiratory flow rate in Sri Lankan schoolchildren of Sinhalese ethnic origin. AB - Normal values for lung function indices are not available for Sri Lankan children. Reference standards for peak expiratory flow rate (PEFR) in non-smoking Sri Lankan schoolchildren belonging to the Sinhalese ethnic group have been derived. A total of 1206 schoolchildren of age range 5-19 years was studied. The mini-Wright peak flow meter was used to measure peak expiratory flow rates. The highest of three readings was taken as the correct value. The results were correlated with age, standing height, weight and surface area. The flow rate was only marginally higher in pre-pubertal boys than in girls. Girls reached a maximum at 15 years of age. The boys continued to show an increase in the PEFR until, at the age of 19 years, they had values about 150 l min-1 higher than females of the same age. Up to a height of 150 cm, a weight of 35 kg and l.1 m2 surface area, the two sexes showed similar gradients of increase of PEFR. Beyond these limits, the relationships changed abruptly, the boys showing an increase and the girls, a decrease in the gradient. There was a high correlation between PEFR and the anthropometric measurements studied. The peak flow rates compared favourably with those of other ethnic groups. Prediction formulae were developed with age and height as the independent variables. A nomogram based on these equations was constructed. These results would be useful in obtaining predicted normal values in Sinhalese school children with respiratory dysfunction. PMID- 8209072 TI - Comparison of the effects on lung function of two methods of bronchodilator administration. AB - The aim of this study was to assess if administration of bronchodilator via a metered dose inhaler (MDI), rather than by a nebulizer, avoided the early paradoxical deterioration in lung function but, resulted in equally effective late bronchodilation. Fifteen children were studied at a median postnatal age of 9 months (range 9-18), all had been born prematurely at a median gestational age of 27 weeks (range 23-31). Lung function was measured by plethysmography before and 10 min after normal saline and 5 and 15 min after salbutamol given via an MDI and a nebulizer in random order. At 5 min, compared to baseline values, airways resistance (RAW) deteriorated by 16% after nebulized salbutamol but improved by 3% following salbutamol by the MDI (P < 0.03). At 15 min RAW improved by 14% following nebulized salbutamol and 15% after salbutamol via the MDI, there was no significant difference in the magnitude of bronchodilation between the two methods of administration. Our results therefore suggest, that as the early paradoxical deterioration in lung function is usually avoided by administering salbutamol via an MDI, this should be the preferred method of administration. PMID- 8209073 TI - Flow volume curves in children with cystic fibrosis--a possible risk of cross infection? PMID- 8209074 TI - Can topical zinc accentuate tuberculin reactivity in the elderly? PMID- 8209075 TI - Acute renal failure in fulminant psittacosis. PMID- 8209076 TI - [Epidemiology is a singular science]. PMID- 8209077 TI - The relation between antenatal care and birth weight. AB - The relation between gestational age at first antenatal visit and infant's birth weight was investigated in a cohort study of 846 primiparas living in the City of Dundee, Scotland, whose first antenatal visit was between 1 May 1985 and 30 April 1986. The earlier in pregnancy the first antenatal visit the greater the infants' birth weights tended to be (p < 0.01). The relation was independent of gestational age at birth, mother's age and height, social class, tobacco and alcohol consumption and the child's sex. The result supports similar findings elsewhere, but is more robust in that, in contrast to other studies, all birth weights were measured on a single electronic scale and the effects of maternal tobacco and alcohol consumption on birth weight were taken into account in the analysis. The mechanism of the effect remains to be determined but needs to be identified as it may indicate possible preventive measures for the benefit of future children. PMID- 8209078 TI - Alcohol consumption among high school students and young athletes in north Italy. AB - Alcohol consumption was assessed among 366 male high school students and 330 young men playing in sports teams. On the average, the athletes drank less wine, beer and spirits than the students and reported fewer drunkenness episodes. The association of alcohol drinking with sporting activity and with some independent variables was estimated by logistic regression techniques, fitting models for ordinal or nominal response variables. Point estimates of the odds ratios and their confidence limits showed: 1) an inverse relationship between alcohol drinking and sporting activity, especially as regards the consumption of spirits; 2) a strong positive relationship of alcohol drinking with both experimental and regular smoking; 3) peer alcohol drinking (best friend's and girlfriend's drinking) was the strongest predictor of the participant's alcohol consumption. PMID- 8209079 TI - [Psychiatric diagnosis and cause of death in a hospitalized population]. AB - Psychosomatic theories suggest that psychiatric pathology modulates mortality rates; some diagnoses could be considered as risk factors and others as protective factors regarding the different causes of death. The results obtained so far are controversial. The present study aimed at determining the associations between psychiatric diagnosis and cause of death on the basis of 1698 deaths which occurred in a regional Swiss psychiatric hospital during the 1945-1989 period. The diagnoses were divided into four groups (psycho-organic syndromes/dysthymia/schizophrenia/others) and the causes of death into five groups (cardiovascular/lung diseases/cancer/suicide/others). As data were lacking for the entire group of hospitalized patients, associations were analyzed by way of a proportional approach (PMR). The proportional variation factors attributed to a given cause were studied by logistic regression (case-control design). The results mainly reveal the specificity of dysthymic patients which were characterized by a decreasing proportion of deaths due to pulmonary diseases and an increasing proportion of deaths due to cardio-vascular disease. Suicide was proportionally more frequent in both dysthymic and schizophrenic patients. The classic hypothesis that schizophrenics are protected against cancer was not confirmed. The limits of the proportional approach (PMR) are discussed. PMID- 8209080 TI - [Psychotropic drug use in adolescence: why more girls? Study of a sample of 12-20 year-old students in Haute-Marne (France)]. AB - As part of a cross-sectional survey on adolescent health, psychotropic drug use was investigated by a self-administered questionnaire on school based adolescents aged 12-20 years (N = 3,279). 27.5% of the girls and 13.8% of the boys had taken a psychotropic drug during the 12 previous months. Female overuse was observed for different types of drugs (for distress/anxiety, sleep disturbance...) whether prescribed or not. Increased use with age was more marked for girls (14.3% to 36.2%) than for boys (10.7 to 16.9%). Psychotropic drug use increased with depressiveness, somatic complaints and medical care. A logistic regression analysis showed that female consumption was still slightly higher than that of boys after adjustment on other related factors. PMID- 8209081 TI - [Job exposure matrices]. AB - During the last years, the use of Job Exposure Matrices (JEMs) for the evaluation of past occupational exposures has grown. This approach is described in this paper. The definition of a JEM is provided. The development process of a JEM is discussed. It includes the choice of the job classification system which influences the degree to which the matrix can be used in other studies, the precise definition of exposures and the choice of entries which should provide more information than the oversimplified exposed/non exposed dichotomy. When comparing JEMs and experts' evaluation of exposure, all aspects of both methods have to be looked at and a balance struck between the advantages and shortcomings of each of them. The problem should not be reduced to a single choice between the precision provided by experts, and the cost savings and standardization offered by JEMs. Statistical analysis with a JEM must be adapted to the job classified information it provided. When an appropriate method is used, the loss of power with a JEM compared to experts' evaluation is rather small or even null. Finally, it is important to avoid a systematic opposition between JEMs and expert assessments, as one positive result of their comparison may be the improvement of both methods of exposure evaluation. PMID- 8209082 TI - [Integration of patients' preferences in individual and collective health choices]. AB - The objectives of contemporary medicine are basically to attenuate the consequences of chronic diseases and to improve the quality of life of the patient. All medical disciplines tend now to elicit therapeutic protocols directly from the general appreciation of the patients. The community is trying to obtain a transnosographic indicator which would allow the effects of its strategic choices between different areas of the health care system to be measured, taking into account the implications on the quality of life of the population. Individual preferences are now at the center of the decision-making process. Different experimental methods are being used to reveal them. Psychometricians use direct observation of a subject's reactions in a particular pathological situation: patients are asked to arrange the intensity of the impacts on bipolar numeric scales, but an actual metrical measure is not yet available. Traditionally, economists believe that in a market, only the consumer's choices enable us to estimate his level of satisfaction. In the health care field, where market mechanisms are not fully operational, they tend to extract the patients preferences through forced choices between hypothetical health states. A real metrical measure is thus obtained. The objective of this article is to exhibit these two methods: psychometric and economic, and to show how they have been implemented in French field research to obtain quality adjusted life years indicators: QALY's. PMID- 8209083 TI - [Is prevention of colorectal cancer possible?]. PMID- 8209084 TI - [Myocardial infarct following intense physical effort]. PMID- 8209085 TI - [Evaluation of the surveillance policies of infectious diseases in France]. PMID- 8209086 TI - [Nitric oxide: an intercellular gas with physiological and toxic actions. New perspectives]. PMID- 8209087 TI - [The spectral analysis of heart rate variability. The methodological aspects]. AB - OBJECTIVES: A study is made of the influence of methodology on the analysis of cardiac cycle variability in terms of frequency and time domains. METHODS: Twenty five individuals were divided into three groups: 1) non-smokers (n = 10); 2) smokers (n = 8); and 3) non-smokers without guided respiratory frequency (n = 7). An analysis was made of RR variability during 5 min intervals in time domain (standard deviation, variation coefficient, and difference between maximum and minimum RR), and frequency domain (spectral analysis, Fast Fourier Transform algorithm using 5 types of data windows). RESULTS: On comparing the results obtained in the 25 individuals with the 5 data windows, significant differences were observed (ANOVA; p < 0.001) in maximum and total amplitudes of the spectrum (in absolute terms) in the low frequency band (0.04-0.15 Hz). No significant differences were found between the normalized values or between the low/high (0.15-0.40 Hz) frequency ratio: W1 = 1.63 +/- 0.30; W2 = 1.62 +/- 0.29; W3 = 1.65 +/- 0.31; W4 = 1.52 +/- 0.26, and W5 = 1.55 +/- 0.27 (X +/- SE). On averaging the RR intervals each 5 cycles, significant differences were encountered for great part of the parameters studied. No significant differences were encountered for great part of the parameters studied. No significant differences were noted between the non-smokers as regards the use or non-use of a metronome (low/high frequency ratio in group 1 = 1.85 +/- 0.39 vs group 3 = 1.78 +/- 0.43; NS). The linear regressions between the variability parameters in terms of time and frequency domains (absolute values), and age (group 1) were significant, with greater regression coefficients on using the linear transformation of an exponential model. On comparing groups 1 and 2, a non statistically significant trend towards smaller maximum and total amplitudes (absolute values) was noted in group 2 for both frequency bands. CONCLUSIONS: 1) The type of data window (Fourier analysis) introduces significant modifications of some parameters expressed in absolute values, but not between normalized values; 2) signal averaging greatly modifies the information obtained; 3) the decrease in variability parameters observed with age fits better to an exponential model; 4) no differences were detected on guiding or not respiratory frequency, and 5) smoking appears to induce a tendency towards reducing cardiac cycle variability. PMID- 8209088 TI - [A comparison of echocardiography with dobutamine administration and the stress test in detecting coronary disease]. AB - INTRODUCTION: Echocardiography with dobutamine has been proposed as a useful tool in the diagnosis and assessment of coronary artery disease. PATIENTS AND METHODS: To determine the usefulness of echocardiography combined with dobutamine infusion (10 micrograms/kg/min, with increments of 10 micrograms/kg/min every 3 min up to 40 micrograms/kg/min) and atropine if submaximal heart rate is not achieved in detecting coronary artery disease, 45 patients with chest pain underwent this test, exercise stress test and coronary angiography. RESULTS: No significant differences were found between double product (peak heart rate x systolic pressure) after dobutamine infusion (18,774) and after exercise (16,950; p = NS). Significant coronary artery disease, defined as having 70% stenosis in, at least, one major vessel, was present in 30 patients. Although overall sensitivity of dobutamine echocardiography test (70%) was similar than that obtained by exercise stress test (66%), sensitivity of the subgroup of patients with single-vessel disease was significantly higher (66 vs 42%, respectively; p < 0.05). Specificity was slightly higher with dobutamine echocardiography test (94%) than with exercise stress test (66%; p = 0.07). Side effects and major complications (hypotension, ventricular tachycardia, heart failure) were present in 8 (18%) and 3 (6%) patients, respectively. ECG during dobutamine administration become positive for ischemia in 17 patients with and 1 without coronary artery disease. CONCLUSIONS: Dobutamine echocardiography test is highly sensitive and specific for the detection of coronary artery disease. Its sensitivity in patients with single-vessel disease is better than that obtained by exercise stress test. Complications after dobutamine infusion must be kept in mind. PMID- 8209089 TI - [The surgical treatment of sustained ventricular tachycardias. The short- and midterm results in the era of the implantable defibrillator and the heart transplant]. AB - BACKGROUND: The surgical treatment of refractory ventricular tachycardia has been shown to be effective. Its use has been limited by a high perioperative mortality. OBJECTIVE: To study the extent to which the introduction of new therapeutic options, i.e. the implantable defibrillator and cardiac transplantation, improves patient selection and results of direct antiarrhythmic surgery. PATIENTS AND METHODS: We analyzed 24 consecutive patients operated upon for ventricular tachycardia (study population). At the same time, 42 patients were treated with implantable defibrillator and 11 patients, with symptomatic ventricular arrhythmias, underwent cardiac transplantation (reference population). RESULTS: The clinical characteristics of the study population (age, functional class, ejection fraction) were significantly different from those of both reference groups. Nine patients (38%) were operated upon because of electrical instability and/or contraindication for other therapeutic options despite of having criteria of high surgical risk. There was one perioperative death (4.2%) and no other early arrhythmic recurrences. Persistence of inducibility occurred in 5 cases (22%). During follow up (35 +/- 22 months) there was a single arrhythmic recurrence. Three patients died of nonarrhythmic causes. Presently, 16 patients are in I or II NYHA functional class. CONCLUSIONS: 1) Direct surgery remains as a useful tool in the treatment of ventricular tachycardia; 2) clinical differences among groups caused by the individual selection of the three therapeutic options preclude comparison of their results, and 3) the introduction of other therapeutic approaches, although resulting in only partial improvement of patient selection, leads to acceptable short and mid term results of direct antiarrhythmic surgery. PMID- 8209090 TI - [Is the direct surgery of ventricular tachycardias a valid option in the era of implantable defibrillators?]. PMID- 8209092 TI - [Balloon percutaneous angioplasty in postoperative aortic coarctation]. AB - BACKGROUND: Percutaneous transluminal balloon angioplasty has been documented as a useful procedure in the treatment of recurrent coarctation of the aorta. In this project we present our experience and results. PATIENTS AND METHODS: Percutaneous transluminal balloon angioplasty was performed in 7 children with postsurgical coarctation of the aorta. Six of them had previous coarctation of the aorta and one had a iatrogenic result of a persistent ductus arteriosus operation. RESULTS: Mean pressure difference across the coarctation decreased from mean = 51 +/- 16 mmHg to mean = 14 +/- 6 mmHg after the angioplasty and mean diameter of the aortic lumen at the coarctation site increased from mean = 3.6 +/ 1.4 to mean = 8.7 +/- 1.2 mm. All patients are asymptomatic and normotensive at least during the following two years after the procedure. Only the patient who had iatrogenic coarctation still has a residual gradient of 30 mmHg. There were not any major complications during the procedure or after it. CONCLUSIONS: Percutaneous transluminal balloon angioplasty is a safe and effective procedure in the treatment of postsurgical coarctation of the aorta. PMID- 8209091 TI - [Radiofrequency ablation of the slow nodal pathway in cases of paroxysmal nodal reentry tachycardia]. AB - INTRODUCTION: We describe our experience in the treatment of supraventricular tachycardia due to atrioventricular nodal reentry by radiofrequency catheter ablation of the slow pathway. PATIENTS AND METHODS: Thirty-four patients (mean age 52 +/- 13 years) with recurrent drug refractory atrioventricular nodal reentrant tachycardia underwent radiofrequency catheter ablation of slow-pathway as the first procedure. Maximal energy used was 28 +/- 8 W, mean time was 4.4 +/- 2.8 min, and a mean number of 13 +/- 9 discharges per patient. RESULTS: Of the 34 patients 14 were successfully treated (no slow-pathway conduction, no AV nodal reentrant echo complexes, no inducible tachycardia), 11 were considered as partially successful (no inducible tachycardia, with slow-pathway conduction or echoes) and 9 patients were unsuccessfully treated (all of them underwent fast pathway ablation with a successful outcome). Eight recurrences were observed during a mean follow-up period of 7 +/- 4 months: One in a patient with previously successful ablation (remained asymptomatic while taking beta blockers), 6 in patients with first procedure partially successful (all of them underwent effective second slow-pathway ablation) and 1 in a patient with an unsuccessful procedure that underwent fast pathway ablation. A repeated procedure was successful in ablating the slow pathway. None of our patients developed complete atrio-ventricular block. One patient developed cardiac tamponade that needed surgical drainage. At last follow-up all patients are free from tachycardias. CONCLUSION: Slow pathway ablation is an effective method of treatment in patients with atrio-ventricular nodal reentrant tachycardia. Long term success is related to complete abolition of slow pathway conduction. PMID- 8209093 TI - [Congenital anomalies of the origin of the coronary arteries. The diagnostic and therapeutic aspects]. AB - We report 5 cases of congenital coronary artery anomalies. Two involving the right coronary artery arise from the left sinus of Valsalva, two of the circumflex artery arise from the right sinus of Valsalva and a patient with the left coronary artery arise from the right coronary ostium and passes obliquely posteriorly behind the right ventricular outflow tract and the aorta suffering an acute myocardial infarction and coronary artery by-pass surgery was performed in the acute phase. PMID- 8209094 TI - [Emboligenic mitral papillary fibroelastoma and positive antiphospholipid antibodies]. AB - Cardiac papillary fibroelastoma has been associated to high levels of antiphospholipid antibodies, either primary or in the context of systemic lupus erythematosus. We present the case of a young female with several episodes of peripheral emboli. Two-dimensional echocardiography demonstrated a tumor on the anterior mitral leaflet. The mass was resected and histologically showed a papillary architecture covered by hyperplasic endocardial cells on a layer of connective tissue and a central core of collagen and elastic fibers. The immunologic study demonstrated high titers of anticardiolipin antibodies, complement consumption and positive antinuclear antibodies. The patient keep high anticardiolipin antibodies titers at follow-up but embolization has not recurred and has no symptoms. PMID- 8209095 TI - [Aortic insufficiency in an asymptomatic girl: valve prolapse as the only finding]. AB - A case of an asymptomatic 9-year-old girl is reported. She was diagnosed of aortic regurgitation by valvular prolapse without other systemic or valvular pathology associated. We discuss her etiology and physiopathology. PMID- 8209096 TI - Effect of exercise and protein intake on energy expenditure in adolescents. AB - In order to evaluate the influence of physical exercise and protein intake on Resting Metabolic Rate (RMR) and Postprandial Energy Expenditure (PEE), 16 healthy, normal-weight, 15 year-old, adolescent males at the same stage of pubertal development were studied. They were assigned to two dietary groups receiving the same energy intake (1.3 x by measured RMR) and different proportions of macronutrients (13% protein, 39% fat, 48% CHO in Group A; 30% protein, 32% fat, 38% CHO in Group B). An increase in postprandial energy expenditure, relative to basal, was observed in all individuals. The postprandial energy expenditure was higher in group B than in group A. Postprandial Post exercise Thermogenesis (expressed as Kcal/3 h) was significantly higher in group B than group A (p < 0.05). Although the RMR on the test day was not different between the groups, the RMR on day 2 was significantly higher than on day 1 in group B (p < 0.01). In group B, the post-exercise RQ was significantly lower than the preexercise RQ (p < 0.01). It is concluded that in normal-weight-adolescents, a hyperproteic diet followed by moderately-intensive exercise induces increases in EE and decreases in RQ in the postprandial post-exercise period and is accompanied by increase in the RMR the following day. PMID- 8209097 TI - [Transmural electrical stimulation in the reticular groove of adult cattle]. AB - An in vitro study of the smooth muscle of the fore third of the reticular groove bottom was carried out in adult bovines, to determine the most favorable parameters for electrical transmural stimulation (ETS). The mechanical activity of the preparations was registered isometrically and the electric stimuli were applied by means of ring-shaped platinum electrodes. Results show that the response of this tissue to ETS is of a phasic and synchronic nature in accordance with the stimulus. The parameter values necessary to produce a homogeneous, quantifiable and reproducible response were the following: Supermaximum voltage 70-100 V, frequency 30 Hz, pulsing time 4 ms, stimulus time 5 s and intervals between each stimulus 4 min. The intervals among stimuli where 3 min long to establish the frequency curves of 2, 6, 10, 20 and 30 Hz. PMID- 8209098 TI - [Evaluation of the malate dehydrogenase activity in deteriorated sunflower seeds]. AB - Malate dehydrogenase (MDH) activity in sunflower (Helianthus annus L. cv. Peredovik) seeds stored at 65 degrees C and 90 degrees C for 1, 3, 5, 7, and 14 days was evaluated. This study was design to discern the usefulness of this viability test for deteriorated seeds. Differences in the resistance to the heat storage were detected between treatments as reflected by changes in the evolution of MDH activity. A decrease of MDH activity in both soluble and mitochondrial fractions was observed, which was more evident in seeds stored at high temperature. These differences are poorly correlated to viability as determined by tetrazolium staining, and should be related to integrity of cellular membranes as evidenced by differential MDH activity in soluble and mitochondrial fractions. PMID- 8209099 TI - Stimulation of phagocytosis against Staphylococcus aureus by teicoplanin and vancomycin. AB - The constructive interference of teicoplanin with phagocytosis of Staphylococcus aureus by murine macrophages and human neutrophils, studied in vivo and in vitro respectively, was compared with that of vancomycin. Both teicoplanin and vancomycin increased the phagocytosis by macrophages. All the concentrations of teicoplanin increased the phagocytosis by neutrophils, but only the highest concentrations of vancomycin (50 mg/l and 100 mg/l) had this effect, greater values being found with teicoplanin in all cases. PMID- 8209100 TI - Effects of bronchoconstriction on the cough reflex in the cat. AB - The present study was aimed to analyse the influence of bronchoconstriction (Carbachol, 10 micrograms/kg, i.v.) on the cough response to mechanical stimulation of the tracheal mucosa. Experiments were performed in anaesthetised and spontaneously breathing cats, using the isolated glottis technique. Airflow, pleural pressure, subglottic pressure, blood pressure and total lung resistance were recorded. During bronchoconstriction, the cough response was inhibited significantly as shown by the decrease in the number of cough efforts (p < 0.001), in maximum flow during inspiratory (p < 0.001) and expiratory (p < 0.001) movements and in the change of the expiratory (p < 0.01) and inspiratory (p < 0.01) pleural pressures. The mechanical stimulation of the tracheal mucosa evoked always a prolonged decrease of the larynx resistance, including those cases with inhibition of the cough. This study shows that the activation of some type of receptors during bronchoconstriction can modify the cough response to mechanical stimulation of the tracheal mucosa. On the other hand, the widening of the glottis, an associated component of the cough response, can be obtained separately, suggesting that the laryngeal response is centrally integrated via different mechanisms. PMID- 8209101 TI - [Chronic renal insufficiency and secondary hyperparathyroidism in rats. Biochemical and histological evaluation]. AB - Chronic renal failure (CRF) in rats (surgical nephrectomy, 5/6) as well as its derived bone lesions have been studied. Eighty-five male Wistar rats were used, to which chronic renal failure was induced in 1 or 2 surgical times, the parameters of renal function in basal conditions and at different times after surgery being determined. With the method used chronic renal failure is induced with values of creatinine clearance 2/3 times lower than the initial ones (p < 0.05), which stabilize at the 7th week. On the other hand the parathyroid hormone levels (PTH) in serum triple (from 125 +/- 49 to 395 +/- 191, p < 0.05), and a decrease in the tubular phosphate reabsorption is produced (p < 0.001). In bone histology an increase in resorption and bone formation is observed as well as paratrabecular fibrosis, all of which is compatible with the histological diagnosis of hyperparathyroidism. The model of surgical renal insufficiency with ablation of 5/6 of the renal mass, reduces renal function to 1/3 of the initial values after 7 weeks, this procedure having a 20% global mortality without differences being observed between the carrying out of nephrectomies in 1 or 2 surgical times. This degree of CRF was accompanied by secondary hyperparathyroidism both at the biochemical and histological levels, findings which are of great usefulness for future experimental studies. PMID- 8209102 TI - In vivo increase of passive intestinal absorption by cotransporter activation in rat. AB - The effect of the luminal exposure to 25 mmol/L galactose, alanine, tryptophan or sorbitol on the passive absorption of 10 mmol/L galactose, mannitol and 2 deoxyglucose has been studied in in vivo perfused rat jejunum. Absorption of mannitol or 2-deoxyglucose is markedly enhanced by the presence of any of the three cotransported substrates, but not by that of the non transportable sorbitol. Furthermore the passive absorption of galactose (measured in the presence of 2 mmol/L phloridzin) increases after alanine active transport, while it remains unmodified after sorbitol exposure. The stimulatory effect on mannitol or 2-deoxyglucose absorption can be observed 5 min after addition of galactose and it is not significantly modified during the 50 min period that followed. The passive absorption increase observed with alanine and especially with galactose seems to be easily reversed by washing with saline solution. With tryptophan, the effect remains after washing but some mucosa desquamation is observed. These results with direct measures confirm the passive absorption stimulation by the activation of Na(+)-substrate cotransporters. The passive absorption may take place by the paracellular way through the tight junctions. PMID- 8209103 TI - [Specific actions of growth factors (EGF and IGF-I) on the in vitro maturation of bovine oocytes]. AB - Growth factors (EGF and IGF-I) have different actions on mammalian cells such as proliferation and differentiation. The effect of EGF and IGF-I was examined on in vitro matured bovine oocytes. Immature oocytes were obtained by follicular aspiration from slaughtered heifer ovaries and classified in two groups, with or without cumulus cells. Oocytes (n = 1,037) were cultured in a serum-free media (TCM-199) for 24 hours at 39 degrees C in absence of hormones and were divided in 5 treatments: control, EGF (20 ng/ml and 50 ng/ml), IGF-I (100 ng/ml) and EGF + IGF-I (50 ng/ml + 100 ng/ml). Results suggest that the EGF + IGF-I treatment increases significantly (p < 0.01) the maturation rate (60.3%) as compared to control medium (36.5%) in cumulus cell-enclosed oocytes. No significant differences were observed between the treatments in the denuded oocytes. The effect of EGF + IGF-I added to the maturation media seems to be mediated by the surrounding cumulus cells and enhanced the in vitro maturation rate on cumulus cell-enclosed bovine oocytes. PMID- 8209104 TI - Reflex apnea and bronchodilation in the cat. PMID- 8209106 TI - [Mycoplasma sp. in the respiratory tract of hospitalized children]. AB - Mycoplasma pneumoniae is one of the most common bacteria causing respiratory diseases in other countries, specially in older children, adolescents and young adults and less frequently in the age group studied here, nevertheless the determination of its presence in this group was considered important. Two hundred and fifty throat swabs were taken from children, under five years of age, hospitalized with a diagnosis of acute respiratory infections (ARI) and to 50 children, same age, with no ARI (controls). The samples were placed in transport media and were incubated at 37 degrees C during 7 to 15 days. They were reinoculated in PPLO agar and typical colonies were looked for, 5 to 8 days later. The organisms were identified by biochemical tests. Eight Mycoplasma sp (3.2%) were obtained, five of them were M. pneumoniae (2.0%) and three M. hominis (1.2%). Only in 2 cases adenoviruses with M. hominis were found in the absence of other pathogens. It was shown that M. pneumoniae also infects children under five years old, so its present should be suspected, specially when the patient's health does not improve with the installed treatment. Some important suggestions for the isolation of mycoplasma are given. PMID- 8209105 TI - [Frequency of intestinal and bacterial parasites producing diarrhea in children in a regional hospital]. AB - The diarrhoea diseases are priority health problems in all countries of the Third World. The number of the cases of diarrhoea and other intestinal infections have very high morbi-mortality rate in mexican childhood. There are many factors that affect these pathologies, those related to social, economic and cultural aspects seem to be the most important. Although the intestinal viruses are frequent, the enteritis produced by bacteria are more severe and acute. There area also parasites that yield the chronic type disease. In this paper, the most frequent parasites and enteropathogenic bacteria infecting children below 15 years old, either hospitalized or being outpatients from the Hospital de Zona No. 29 del IMSS in Mexico City, were studied. The data obtained were related to the socioeconomic level. A total of 415 stool samples were collected from newborn to 14 years old children over a period of nine months. The samples were classified according to the ages, schooling and number of persons who slept with the child in the same bedroom. The samples were examined by a centrifugal concentration technique and by cultivation. The group of children up to five years old were found to be the most infected by bacteria, while children from 10 to 14 years old were by parasites. Those children whose parents either have not finished the elementary school or can not read and write were the most parasitized (40%), these children were also found to be most infected, as the number of persons who slept in the same bedroom increased, the number of infections per children either by bacteria or parasites, also increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209107 TI - [Microbiological study of nosocomial lung infections]. AB - A total of 83 adult patients between 25 and 60 years of age who acquired pulmonary infectious disease within 48 hours after being admitted to the medical, surgical and/or intensive care units at the university hospital of the "Universidad de Los Andes" (Merida, Venezuela) were studied during a period of 18 months. The most frequent clinical entity observed was pneumonia (49.4%). In all types of pulmonary samples obtained by secretion or puncture, more than half gave positive results to the microbiological analysis. Gram-negative bacilli prevailed as the etiological agents, with a preponderance of the species from Klebsiella (21.7%) and Pseudomonas (15.1%) genus. Staphylococcus aureus was also isolated in 13.3% of all cases. Satisfactory sensitivity to third generation cephalosporins and aminoglucosides was observed on these strains. Quinolones showed the highest antimicrobial activity. The application of an adequate antimicrobial therapy, according to the antibiotics sensitivity test results, allowed a successful clinical efficacy in 67.4% of all cases. PMID- 8209108 TI - [Survey of anti-Leptospira agglutinins in workers from the city of Londrina Parana, Brazil]. AB - Serum samples were obtained from 249 individuals in Londrina-Parana, Brazil. The sera were analysed for leptospiral agglutinins by microscopic agglutination tests and 22.1% were positive. Of these positives per group were 24.6% for butchers, 25.9% for farm workers, 17.2% for children and 22.2% for servants. The agglutinin titers ranged from 1:200 to 1:3200. The highest titers were obtained for the serovars sejroe (butchers), grippotyphosa (farm workers), javanica, canicola, panama, wolffi and pyrogenes (children) and butembo (servants). PMID- 8209109 TI - Characteristics of gram-stained cervical smear from patients with Chlamydia trachomatis infection. AB - Cervical discharges from 142 women attending the Public Gynecologic Service of Araraqura (SESA), Brazil were cultured for Chlamydia trachomatis. Gram-smears and plating on semiquantitative sheep blood agar and chocolate agar were also carried out. An isolation rate of 18% was reported. The presence of purulent cervical secretion was observed in 8 (32%) out of 25 women. It was also observed that a substantial proportion of culture-positive women had no symptoms. Our data demonstrate that screening tests should be based on specific diagnostic techniques for Chlamydia trachomatis since the majority of infected women we examined were asymptomatic. PMID- 8209110 TI - A new option for chemical labelling of oligonucleotide probes with biotin molecules. AB - Utilization of molecular probes for identification of pathogenic microorganisms have great advantages if we compare results obtained with classic systems traditionally employed in the clinic and research laboratories. This new method with biotin is more sensitive and specific than others and exclude the use of radioactive markers. PMID- 8209111 TI - Herpes simplex virus infection in primary neuronal cultures and antiviral activity of dsRNA. AB - Central neurons in culture represent a limitless substratum for research in neurobiology and experimental neurology. Primary cultures of NIH mouse neurons have shown that about 83% of total cells in the cultures are neuron clumps, detected by their reaction with the neuron specific-enolase (NSE) marker. Herpes Simplex Virus type 1 (HSV-1) can grow efficiently in these cultures, as it does in nonneuronal cultures usually used for antiviral drugs testing. For that reason, the primary neuronal cultures were used for testing antiviral activity against HSV-1, after an overnight treatment with different concentrations of dsRNA from phi 6 bacteriophage. The dsRNA started to be toxic for the cells at concentrations of 4 micrograms/ml, but it was found that 1 microgram/ml of this dsRNA protected all the neuronal cultures from HSV-1 infection. The dsRNA value for effective dose (ED50) was 0.27 microgram/ml. PMID- 8209112 TI - Differential specific humoral response of susceptible and resistant mice infected with Mycobacterium lepraemurium. AB - C57BL/6 and BALB/c mouse strains were infected intraperitoneally with 10(8) Mycobacterium lepraemurium (MLM). At various stages of the infection, MLM specific IgM, IgG, IgG1 and IgG2a serum antibodies were assessed. Anti-MLM antibody response varied markedly in both strains, in terms of antibody titres, Ig class distribution and kinetics of antibody secretion. C57BL/6 mice, which show intermediate resistance to MLM infection, presented the higher titres of IgM and IgG specific antibody, but without anti-MLM IgG1 detectable production. On the other hand, BALB/c susceptible strain showed a delayed but high IgG1 antibody production. Since it has been reported that Th2 lymphocyte subset modulate IgG1 antibody production, our results may reflect a differential activation of Th1 and Th2 cell subsets in both strains during a MLM infection. PMID- 8209113 TI - [Efficiency of an ELISA using complete and delipidated protein extract from Mycobacterium tuberculosis H37Rv strain as a serological test for ruling out pulmonary tuberculosis]. AB - We present the results of an enzyme-linked immunosorbent assay that detects serum antibodies to M. tuberculosis antigens. The patients sera were tested with two different antigens, one a M. tuberculosis H37Rv culture filtrate protein extract precipitated with ammonium sulfate (CFPE), and the second, a delipidized CFPE (CFPE-d). The results obtained with 52 clearly defined TBP patients was 0.50 +/- 0.16 (CFPE) and 0.38 +/- 0.11 (CFPE-d). We also tested 165 sera from patients hospitalized at the INER with a diagnosis of non-tuberculous pulmonary disease. In this patients the assay revealed 153 negative sera (CFPE = 0.053 +/- 0.01; CFPE-d 0 0.050 +/- 0.004) and 12 positive sera. Nine of these patients (CFPE = 0.38 +/- 0.08; CFPE-d = 0.32 +/- 0.09) had mycobacterias and the results of the remaining three were considered as false positive. TBP was excluded in all the 153 negative patients. The elimination of lipids in the CFPE did not alter the assay since the differences between CFPE and CFPE-d did not reach statistical significance. In non-tuberculous individuals the reactivity with mycobacterial lipids was poor and didn't induce false positive results. The assay we report can be useful in those patients with pulmonary disease where TBP has to be considered. PMID- 8209114 TI - [Sporothrix schenckii: cultures in different soils]. AB - In order to establish the conditions of temperature, pH, and organic material which favor the development of Sporothrix schenkii, the cultures of this fungus were examined in media consisting of potting soil, clay, white land and sand. The results indicate that the content of organic material in the soils is fundamental for mycelium development. The fungus shows growth in the soils rich in cellulose in the pH range from 3.5 to 9.4 and temperature of 31 degrees C. the development of the mycelium does not show alterations in phenotypical characteristics. These results show the distributions that S. schenkii can have in the soils, which can be transmission vehicles of sporotrichosis. PMID- 8209115 TI - [Comparative study of the susceptibility of 5 triatomine species (Insecta: Reduviidae) to Trypanosoma cruzi infection]. AB - In order to determine the most suitable species of triatomine for xenodiagnosis of the Chagas disease, five species triatomine (Triatoma barberi, T. infestans, T. pallidipennis, T. phyllosoma, and Rhodnius prolixus) in third and fourth instars were used to evaluate their susceptibility to one T. cruzi strain isolated in Mexico. The susceptibility was determined by: a) percentage of infected triatomines, b) amount of flagellates in bug feces and c) amount of blood ingested. We found that in most species of triatomines tested the third instar was more susceptible than fourth instar. The order of susceptibility to T. cruzi was: T. pallidipennis > T. barberi > T. phyllosoma > T. infestans > R. prolixus. PMID- 8209116 TI - [IgG antibodies against Toxoplasma gondii in Cuban blood donors]. AB - Sera from 1036 donors at the Hemotherapy Service of the General Hospital "Luis Diaz Soto" were evaluated for IgG anti-Toxoplasma gondii antibodies. No significant difference was found among sexes. The presence of T. gondii antibodies were distributed in eight age categories; a minor and a major presence of specific IgG for the young and old age groups, respectively was found. The relationship of specific antibodies and ABO blood groups were considered for the masculine gender. The AB blood group a significant difference (P < 0.05), except for the B blood group in the rate of T. gondii antibodies. PMID- 8209117 TI - [Frequency of vaginal trichomoniasis and candidiasis and its relation to the clinical profile]. AB - Eight hundred samples of vaginal swabs were taken from women with active sexual life attending the Cervicouterine Cancer Opportune Detection Service at the Familial Medicine Unit No. 18 of the National Institute of Social Security, to study the incidence and prevalence of vaginal trichomoniasis, the presence of yeasts of the genus Candida and their relationships with clinical features of vulvovaginitis. Identification of parasites was made by means of direct examination with light microscope; 14.39 per cent of candida vulvovaginitis against 3.13 per cent of trichomoniasis was found; in only five cases the two parasites were associated. Leukorrhea and vaginal pruritus were the major symptoms found and the most affected anatomical regions were vaginal walls in trichomoniasis and cervix in candidiasis. Although vaginal trichomoniasis is a worldwide distributed parasitosis, its frequency is very variable, not so vaginal candidiasis, which is more frequent. PMID- 8209118 TI - [Polymerase chain reaction (PCR) in clinical diagnosis. Review of the use of the technique]. AB - The use in clinical diagnosis of the polymerase chain reaction (PCR) technique is reviewed. This method consists of the amplification of a single molecule of DNA (50 to 2000 base pairs in length) to more than a million copies of DNA in a few hours. Relevant advantages of this technique are its specificity, sensitivity and ability to amplify impure DNA. Diagnostic methods for diagnosis of infectious diseases and genetic disorders in humans have been developed recently. PMID- 8209119 TI - [How I treat... a patient with obesity]. PMID- 8209120 TI - [Various practical schemes of substitution hormone therapy]. PMID- 8209121 TI - [Which treatment for menopause in case of gynecological cancer?]. PMID- 8209122 TI - [Prevention of postmenopausal osteoporosis in case of contraindications of estrogens]. PMID- 8209123 TI - [Menopause and aging of the skin]. PMID- 8209124 TI - [Introduction to tropical dermatology]. PMID- 8209125 TI - [Ethics (significance and history)]. PMID- 8209126 TI - [Drug of the month. Paroxetine (Seroxar, Aropax)]. PMID- 8209127 TI - [Polymerase chain reaction: basic principles]. AB - The Polymerase Chain Reaction is a technique in molecular biology, that allows million-fold amplification of DNA-fragments. It is based on specific oligonucleotides used as starting segments (primers) of both sides of the genomic region to be studied. This chain reaction is characterized by three steps: denaturation of DNA by increasing the temperature; renaturation of the DNA allowing for competition between the two original DNA segments and the numerous primers, and finally synthesis of DNA by the polymerase. The cycle is repeated from 25 to 35 times in order to exponentially duplicate the DNA-fragments between the two primers. Usage of a thermoresistant polymerase permitted automatization of the procedure. This technique represents a revolution for practical molecular biology and medicine. Its very high sensitivity, however, may cause errors that have to be recognized. Several practical examples are described and analyzed in order to illustrate the PCR-concept to physicians in practise. PMID- 8209128 TI - [Diagnosis using PCR: the direct approach]. AB - The direct approach in molecular diagnosis proposes evidences of the mutations underlying the investigated diseases. Due to its speed, specificity and low cost, the Polymerase Chain Reaction (PCR) has become the method of choice in most of these analyses. The direct approach can be either positive or negative. In the first case, the diagnosis is based on the presence of a pathognomonic PCR product, while in the latter, it is the absence of such a product that makes the diagnosis possible. It is evident that both methods have to be validated by several control reactions. Examples out of daily practice illustrate various diagnostic areas. PMID- 8209130 TI - [PCR and cancer]. AB - PCR can be used at different levels in oncology as many examples illustrate. Interchromosomal translocations that can be detected by PCR are very specifically found i.e. in follicular lymphomas. In the context of follow-up controls this may reduce recurrencies. By the identification of genetic lesions of an oncogene, aggressivity of a tumor may be estimated. PCR allows rapid analysis of such lesions. Analysing deletions of tumor suppressor-genes gains increasing importance in oncology. By amplification of microsatellites, presence of such a deletion may be detected. This analysis is not only important for studies of sporadic tumors but may also indicate in individual cases if the patient carries a predisposition for a certain tumor. PMID- 8209129 TI - [Diagnosis using PCR: the indirect approach]. AB - The goal of indirect molecular diagnostic techniques is the detection of a link between a specific allele of a polymorphic genomic marker and a given disease. This technique is used in two specific clinical situations: 1) when the gene is unknown and the search for a mutation or a gene product is impossible 2) when the gene is known but large and several mutations might be present. If none of the known mutations prevails in the local population the systematic and sequential search for every single mutation is not economical. A linkage study is required in those instances. The indirect analysis was up to the nineties based on markers detecting DNA-restriction fragments of various length. By the amplification of microsatellites by PCR the indirect approach has brought enormous progress. Together with the mapping by the Human Genome Project it will progress further. Although indirect molecular methodology can often avoid extended work it is only applicable to families with a member already affected by the disease. DNA from this individual is needed for the detection of a link of one allele to the disease. This means necessarily that the disease must be inherited and that the diagnosis is certain. Presymptomatic molecular diagnosis is illustrated by the analysis of a pedigree with familial adenomatous polyposis by microsatellite PCR techniques. PMID- 8209131 TI - [Nucleic probes and PCR: application in the diagnosis of bacterial infections]. AB - Probes and amplification systems represent new technologic developments in the domain of clinical microbiology. In spite of their high specificity, simple applicability and high velocity the DNA probes show only little sensitivity especially for the direct detection of microorganisms in clinical samples. This sensitivity lead to the development of DNA-amplification technics. PCR is the most famous of them and the most often used one. Next to the direct detection of microorganisms in clinical samples without culture these technics also allow the direct isolation of bacterial toxins, of genes for resistance to antibiotics as well as a systematic search for pathogens in diseases with unknown cause. Different problems of these methods in daily clinical practice are illustrated by four applications 1. direct detection of mycobacterium tuberculosis complex (M. tbc) in clinical samples, 2. rapid identification of mycobacterial species, 3. their typing for epidemiologic intentions, 4. rapid detection of resistance to antibiotics. PMID- 8209133 TI - [Identification of genital papillomavirus using PCR]. AB - Over 20 different types of human papillomaviruses (HPV) are associated with tumoral lesions of the anogenital tract. Some of these lesions may become cancerous at a frequency which depends, among other risk factors, upon the type of HPV. Genital papillomaviruses with high oncogenic risk (HPV16, 18, 31, 33, 35 ...) are associated with the majority of cervical cancers and to a high proportion of high grade anogenital lesions, while HPV6 and HPV11 are most often associated with benign condylomas. The recently introduced PCR (Polymerase Chain Reaction) has distinctly simplified and improved detection and typing of genital HPVs. PCR detection of HPV has its place in epidemiologic studies and basic research, its application in daily clinical practise is, however, still controversial. For routine analysis, PCR serves more as a complementary tool to cytology. PMID- 8209132 TI - [The contribution of PCR to the diagnosis and follow-up of HIV infection]. AB - PCR permits diagnosis of HIV infection by the detection of proviral DNA sequences in circulating lymphocytes. It is the method of choice for diagnosing infection in children born to seropositive mothers. PCR is also a helpful tool when the result of serodiagnosis remains indeterminate of atypical. It may allow the diagnosis of HIV infection before p24 antigen and antibodies become detectable. However, its effectiveness for early diagnosis should still be investigated systematically. The routine application of PCR is problematic at the moment because this technique is highly complex and time-consuming. Future developments should aim on one hand at a simplification of the technique and on the other hand at possibilities for quantitation. By allowing measurement of viral burden (provirus frequency in lymphocytes, virus concentration in plasma), PCR will be a decisive aid for follow-up controls of seropositive patients. PMID- 8209134 TI - [The use of PCR for detecting pathogenic microorganisms in water]. AB - This replication method, which was introduced in 1985, has been used to find and identify microorganisms in the environment, among others in samples of soil, sediments and waters. A gene or a DNA fragment specific to a microorganism is replicated in vitro by a chain reaction catalyzed by DNA polymerase (PCR: Polymerase Chain Reaction) and analyzed by electrophoretic procedures. At the moment in most legislations bacteriological criteria for drinking water depend on E. coli and other bacteria referring to fecal contamination (fecal coliforms and enterococci). Absence of these bacteria does not necessarily exclude contamination of water with protozoa or virus. Detection of the latter by common methods is difficult and time-consuming. Application of PCR to these purposes is interesting. During the last years several protocols have been developed such as methods for the detection of E. coli, bacteria referring to fecal contamination, pathogens like Legionella pneumophila as well as Salmonella and Shigella, enterovirus and protozoa i.e. Giardia. Compared to the traditional methods an obvious advantage of the new methods lies in their velocity, sensitivity and specificity. This review introduces to several different applications of PCR. Although this method is still restricted to specialized laboratories at the moment, it will gain importance as a complement to traditional methods for the detection of pathogenic microorganisms in water as soon as simple tests will be available. PMID- 8209135 TI - Isoforms of the Na,K-ATPase: family members in search of function. PMID- 8209136 TI - Skeletal muscle satellite cells. AB - Evidence now suggests that satellite cells constitute a class of myogenic cells that differ distinctly from other embryonic myoblasts. Satellite cells arise from somites and first appear as a distinct myoblast type well before birth. Satellite cells from different muscles cannot be functionally distinguished from one another and are able to provide nuclei to all fibers without regard to phenotype. Thus, it is difficult to ascribe any significant function to establishing or stabilizing fiber type, even during regeneration. Within a muscle, satellite cells exhibit marked heterogeneity with respect to their proliferative behavior. The satellite cell population on a fiber can be partitioned into those that function as stem cells and those which are readily available for fusion. Recent studies have shown that the cells are not simply spindle shaped, but are very diverse in their morphology and have multiple branches emanating from the poles of the cells. This finding is consistent with other studies indicating that the cells have the capacity for extensive migration within, and perhaps between, muscles. Complexity of cell shape usually reflects increased cytoplasmic volume and organelles including a well developed Golgi, and is usually associated with growing postnatal muscle or muscles undergoing some form of induced adaptive change or repair. The appearance of activated satellite cells suggests some function of the cells in the adaptive process through elaboration and secretion of a product. Significant advances have been made in determining the potential secretion products that satellite cells make. The manner in which satellite cell proliferative and fusion behavior is controlled has also been studied. There seems to be little doubt that cellcell coupling is not how satellite cells and myofibers communicate. Rather satellite cell regulation is through a number of potential growth factors that arise from a number of sources. Critical to the understanding of this form of control is to determine which of the many growth factors that can alter satellite cell behavior in vitro are at work in vivo. Little work has been done to determine what controls are at work after a regeneration response has been initiated. It seems likely that, after injury, growth factors are liberated through proteolytic activity and initiate an activation process whereby cells enter into a proliferative phase. After myofibers are formed, it also seems likely that satellite cell behavior is regulated through diffusible factors arising from the fibers rather than continuous control by circulating factors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8209137 TI - Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport. PMID- 8209138 TI - Complexity and versatility of the transcriptional response to cAMP. PMID- 8209139 TI - Suppression of ras oncogene-mediated transformation. PMID- 8209140 TI - Regulation of gene expression by prolactin. PMID- 8209141 TI - [Gynecology and aircraft piloting aptitude]. AB - The consequences of gynecological disorders and pregnancy are reviewed, as well as the impact of the stresses of aerospace on female and feto-maternal physiology. Current regulations leave the physician a high degree of discretion. Most of the restrictions on employment which do exist are not due to gynecological reasons. PMID- 8209142 TI - [Etiologic study of 275 cases of endo-uterine hemorrhage by uterine curettage]. AB - AIM: To determine the incidence of genital hemorrhage, to specify its etiology and define the epidemiological profile of the "hemorrhagic patient". MATERIALS: Retrospective analysis of selected medical case-histories and histological reports for 275 uterine curettages carried out due to a hemorrhagic sign. RESULTS: The incidence was estimated to be 2.7% of consultations. 292 histological lesions were identified, and their severity classified as follows: 53.8% dysfunctional, 20.0% hyperplasia, 5.5% malignant and 20.5% classified as "rare". The profile was that of a perimenopausal, multiparous woman, obese with normal menarche and menstrual cycle. CONCLUSION: In the general population, genital hemorrhage is less and less frequently indicative of a malignant lesion. PMID- 8209143 TI - [Rupture of a scarred gravid uterus at 28 weeks of amenorrhea. Conservative surgical management and results]. AB - Rupture of a scarred uterus during pregnancy is unusual, but remains a complication with serious consequences for both mother and fetus. It usually occurs towards the term of gestation and the case reported here is of interest because, atypically, the rupture of the uterus occurred some time before term in a scarred uterus and the immediate care provided was conservative surgery. The rest of the pregnancy proceeded to a successful outcome at term under clinical and obstetrical follow-up. The authors also highlight the additional precautions required in medically-assisted pregnancies in patients over 40 years of age. PMID- 8209144 TI - [Role of the gynecologist in the prevention of hepatitis B, especially in the adolescent]. PMID- 8209145 TI - [Estrogen and progesterone receptors in the human placenta]. AB - The author demonstrates the presence of estrogen and progesterone receptors in the trophoblast. He also refers to their distribution within the cytosol and the nucleus, and also discusses their diversity in the various parts of the placenta. He did not detect any difference between placentas obtained from normal deliveries and those obtained after cesarean deliveries. PMID- 8209147 TI - [Science vs. technology vs. marketing: the case of video-assisted endoscopic surgery]. PMID- 8209146 TI - [A new stage, a new image and a challenge...]. PMID- 8209148 TI - [Primary liver cancer. Its epidemiological, clinical and biochemical characteristics]. AB - Epidemiological, clinical, biochemical and topographic features of primary hepatic cancer (PHC) were reviewed retrospective and prospectively in this study. This review consisted of 76 patients from 1971 to 1990. Forty nine males and 27 females. The mean age was 66.1 +/- 11.7 years. Hepatocellular carcinoma (HC) was the most frequent histological type (84.1%), followed by cholangiocarcinoma (87.7%). Mixed carcinoma and hepatoblastoma were 4.3 and 2.9% respectively. The prevalence af PHC among 1485 autopsies was 0.74%. The most frequent sites af metastasis were the lungs (66%) and portal vein (50%). Hepatocellular carcinoma was associated to cirrhosis in 80% of the cases. A syndrome including asthenia, weight loss, hepatomegaly and cholestasis was identified in most of the patients, and alkaline phosphatase was the most frequently disturbed laboratory test. 60% of tumors were bilateral and none of the solitary tumors had less than 5 cms in diameter. 20% of HC showed normal serum levels of AFP (< 20 ng/ml). 40% had at least one of the markers of B virus hepatitis in serum. PMID- 8209149 TI - [Enteral resection in the nursing rabbit (an experimental study)]. AB - The response to enteral resection in human newborns and nursing babies depends on the site and magnitude of the resection: usually these patients have a satisfactory recovery although long term supportive measures are required in order to prevent nutritional and digestive complications. This study assessed the post-surgical response of six groups of nursing rabbits with 0, 40, 50, 60, 75 and 90% selective resection of the small intestine. A greater number of surgical complications was observed in those cases with more manipulation and greater resection. Villi hypertrophic was found at the distal extremes of the enteral remnants only with 40% jejunal resection and 75 and 90% jejunum-ileum resections. None of the groups showed growth interruption. Only in rabbits with resections greater than 60% a significant decrease in weight was found. Forty and sixty percent enteral resections, mainly proximal and distal respectively, did not yield weight or length deficits as compared with the control group. PMID- 8209150 TI - [Biliary calculi in the golden hamster. XXXVII. The prophylactic action of the creosote bush (Larrea tridentata) in pigmented cholelithiasis produced by vitamin A]. AB - In the present work the results of an experiment performed in the golden hamster (Mesocricetus auratus), strain ChCM, are presented, in which the possible preventive action of pigment cholelithiasis by a powdered, desiccated, hydroalcoholic extract of leaves of "gobernadora" (Larrea tridentata) was studied. The extract was added to the lithogenic diet (basic diet + 25,000 I.U. of Vitamin A) at the 4% level; the hamsters were fed with the experimental diets during 70 days. The results showed that the group which received the diet with "gobernadora" did not develop pigment cholelithiasis, whereas the group that received the lithogenic diet alone developed cholelithiasis in 63% of cases. It is suggested that the active principle present in the leaves of "gobernadora", responsible for the prevention of the cholelithiasis is nordihydroguiaretic acid (NDGA), a potent antioxidant. On the other hand, the hamsters that received the diet containing "gobernadora" showed serious signs of toxicity and pathological changes, such as a marked reduction of growth, pronounced irritability and aggressiveness, and a marked hypoplasia both testicular and of the accessory sex glands. PMID- 8209151 TI - [Obesity. Its medico-surgical treatment]. AB - Obesity has been defined as excessive deposition of body fat tissue that risks the health and survival of the patient. It affects almost 30 per cent of whole population in western societies and it's also becoming a common problem in developing countries as rural areas are slowly decreasing in face of urban growing. In Mexico obesity affects as much as 28 per cent of the population of selected urban areas and the trend seems to follow the incidence in North America. There are genetic, environmental, physiological, psychological, social and cultural factors that determine or influence the presence of obesity in modern societies. To date the most accepted approach to the management of this problem lays on 3 main aspects: diet, exercise and behaviour modification. Pharmacological therapy should be limited to selected cases in which associated clinical risks warrant more urgent intervention. Surgical therapy is indicated for morbid obesity in which there is greater than 70 per cent excess weight. Prevention of obesity should remain one of the top priorities in public health and should take genetic, physiological, environmental, social, psychological, cultural and economic factors into consideration. PMID- 8209152 TI - [Cystadenoma of the biliary tract]. AB - The case of a 12-year-old boy with the diagnosis of intrahepatic biliary duct cystadenoma is presented. A critical review of the literature revealed less than 100 cases described at present. Differential diagnosis with other intrahepatic cystic lesions of varied etiology is discussed too. PMID- 8209153 TI - [Massive hemorrhage of the digestive system secondary to ulcerated colonic malacoplakia]. AB - A case of malakoplakia of the colon in a 55-year-old female patient with a massive hemorrhage of the rectum is reported. A barium enema showed polypoid lesions (pseudopolyps). Colonoscopy revealed white-yellowish nodules simulating small pustulae all along the colon at 2 cm from the anal verge. A laparatomy disclosed lobulated intraluminal masses and yellowish lesions in the form of transcolonic plates infiltrating the duodenal wall as well as a fair amount of lymph nodes in the mesentery. We performed a proctocolectomy. The histologic study showed massive infiltrate of histiocytes and numerous Michaelis-Gutmann bodies. This disease is usually found in the urinary tract and rarely found in the colon. The importance of proper histologic examination in order to arrive at a correct diagnosis is emphasized. PMID- 8209154 TI - [Comparative study of larval and ovitrap efficacy for surveillance of dengue and yellow fever vectors]. AB - A comparative study of the efficiency of ovitraps and larval-traps was undertaken with a view to improving the entomological survey of vectors of Dengue and Yellow Fever-Aedes aegypti and Aedes albopictus-in S. Paulo State, Brazil. The region studied is infected only by Aedes albopictus, a species that keeps to wild habitats but colonizes artificial breeding grounds as well. The first part of the study was located in a periurban area of Tremembe county were 3 hollon trees, 23 ovitraps and 5 larval-traps were compared. The second part of these experiments took place in Lavrinhas county (Pinheiros district), where 20 ovitraps and 5 larval-traps were tested. The results showed that the ovitrap was more efficient than larval-traps and were positive even in the presence of natural breeding grounds. It was also observed un the evaluation of the results of "thermonebulization (fog)" that the ovitraps showed strong reduction in the average number of eggs, but this was not observed in the Breteau Index. PMID- 8209155 TI - [Phlebotomine behavior in forest and extraforest environments, in an endemic area of American cutaneous leishmaniasis in northern Parana State, southern Brazil]. AB - Between November 1988 and April 1990, 75,637 phlebotomines were captured with the use of Falcao light traps on Palmital farm in the north of Parana State, Brazil. Fifteen species were represented. The percentage of 95.8% of the insects were captured within the domiciliary area and the remaining 4.2% in the forest environment. The percentage of 62 were captured in one single Falcao light trap installed in a henhouse, where Blancasmya migonei predominated. In all the other traps Psychodopygus whitmani was predominant. B. migonei, P. whitmani, Pintomyia pessoai, Pintomyia fischeri and Psychodopygus intermedius are highly significant vectors of American cutaneous leishmaniasis and represented 93.8% of all phlebotomines captured with 10 Falcao light traps. The monthly densities of these insects were obtained from one Falcao light trap installed in a henhouse and increased especially in the warmer and more humid months. In the forest environment the phlebotomines were captured principally in traps installed about 10 meters above the ground and P. whitmani, B. migonei, P. intermedius, Brumptomyia brumpti, Psychodopygus monticola and P. pessoai were the dominant species. The need for information about the epidemiology of American cutaneous leishmaniasis calls for further investigation with a view to clarifying the implications of the relationship between the phlebotomines and domestic animals in the Leishmania cycle of transmission in domiciliary areas. PMID- 8209156 TI - [Atherosclerotic cardiovascular diseases, dyslipidemia, hypertension, obesity, and diabetes mellitus in a population of the metropolitan area of southeastern Brazil. I--Research methodology]. AB - An epidemiological study was carried out into the risk factors for the following atherosclerotic cardiovascular diseases: lipemic disorders, obesity, hypertension, diabetes mellitus as related to some factors which characterize life-style (sedentary, drinking, smoking and eating habits). The population studied belongs to the metropolitan area of S. Paulo. The research project had the following objectives: a) the development of an epidemiological baseline for the study of the risk factors for the atherosclerotics cardiovascular diseases represented by the lipimic disorders, obesity, hypertension and diabetes mellitus and their relationship with personal, family and social characteristics; b) the for clinical-educative treatment of patients or people at risk. In view of the objectives above it was decided that the project should in an integrated way with the local health centers and community associations in the field work phase. For this purpose, the methodology adopted was that of establishing small geographical areas, denominated "study areas", in accordance with socioeconomic criterion. Clinico-biochemical and eating surveys were carried out and interviews held with a view to obtaining data on socioeconomic and demographic and life-style characteristics. The clinical survey collected data on anthropometric measurements, arterial pressure, electrocardiogram and symptoms of heart disease. The biochemical survey consisted of the measurement of the following constituents of the blood: total cholesterol, HDL cholesterol, triglyceride, magnesium, glucose, sodium, potassium and phosphorous. The eating survey covered data of historic food consumption. By means of indicators such as income, schooling, occupation, position held in the occupation, ownership of property and respective size of property and employment of labour, the social classes were established. The clinico-educative intervention was carried out in the following way: a) the team made contact with the community associations and the health centers, that begin to participate in the project, permitting the use of their physical space for the carrying out of surveys and clinical exams and taking part in the work of publishing and explaining the project; b) those individuals with positive diagnosis or who are found at risk were referred to the health centers which then include assistance for the diseases in question in their permanent activities. After the end the project the team gave to the community a report on the prevalence of the morbidities researched in their population. PMID- 8209157 TI - [Smoking prevalence in the urban locality of southeastern Brazil]. AB - A cross-sectional study for prevalence of arterial hypertension in the population aged 15-74 years of age of the urban area of Araraquara County, 250 km from the city of S. Paulo, S. Paulo, State, Brazil, in 1987, was performed. The questionnaires presented to 1,199 people (533 men and 666 women) at the interview consisted of regarding sociodemographic variables, as well as the use of tobacco (smoking), the ways in which tobacco was used and the habit of inhaling the smoke. The sample was taken by the procedure of clustering, carried out in three stages. The sample was equiprobabilistic. The prevalence of tobacco smoking was very high being of 45.2% for men and 22.8% for women. The ex-smokers accounted for 15.9% of men and 8.0% of women. The men smoked much more than the women. The poorer smoked more than the richer, in both sexes. Among men, the prevalence of smoking was inversely proportional to duration of schooling, but that difference was not noted in women. As there have been other studies regarding the high prevalence of obesity and high blood pressure, it was concluded therefore that the population of Araraquara, an average town of the affluent urban interior of S. Paulo State, has a high frequency of risk factors for chronic non transmissible diseases. PMID- 8209158 TI - [Iron supplementation effects on zinc bioavailability in a regional diet of northeastern Brazil]. AB - The effects of supplementation with iron on the zinc bioavailability of the regional diet of northeastern Brazil (RDN), were investigated. One assay with Wistar rats, feed on RDN and control diets was carried out. The RDN diets contained 16 mg Zn/kg and levels of 35 mg, 70 mg and 140 mg Fe/kg, respectively. The control diets were prepared according to the standards of the Committee on Laboratory Animal Diets, with levels of protein, iron and zinc identical to those of RDN diets. Index of apparent absorption and zinc retained in the femur of the animals were the parameters utilized to measure zinc bioavailability. The results demonstrated that the supplementation with iron decreased the zinc bioavailability, and the effects were seen to affect diet quality and the Fe:Zn ratio. This fact must be taken into consideration in practices such as the fortying of foodstuffs and the administration of vitamin-mineral supplements to populations with nutritional deficiencies. PMID- 8209159 TI - Validity of self-reported weight--a study of urban Brazilian adults. AB - In order to evaluate the validity of self-reported weight for use in obesity prevalence surveys, self-reported weight was compared to measured weight for 659 adults living in the Porto Alegre county, RS Brazil in 1986-87, both weights being obtained by a technician in the individual's home on the same visit. The mean difference between self-reported and measured weight was small (-0.06 +/- 3.16 kg; mean +/- standard deviation), and the correlation between reported and measured weight was high (r = 0.97). Sixty-two percent of participants reported their weight with an error of < 2 kg, 87% with an error of < 4 kg, and 95% with an error of < 6 kg. Underweight individuals overestimated their weight, while obese individuals underestimated theirs (p < 0.05). Men tended to overestimate their weight and women underestimate theirs, this difference between sexes being statistically significant (p = 0.04). The overall prevalence of underweight (body mass index < 20) by reported weight was 11%, by measured weight 13%; the overall prevalence of obesity (body mass index > or = 30) by reported weight was 10%, by measured weight 11%. Thus, the validity of reported weight is acceptable for surveys of the prevalence of ponderosity in similar settings. PMID- 8209160 TI - [Dental caries prevention with semestral topical administration of acidulated phosphate fluoride]. AB - 998 children aged 6, 8 and 10, from low income families living in the Federal District, Brazil and attending public, first grade, schools, received bi-annual topical APF Gel-Tray applications. The mass methodology proposed by the National Dental Caries Preventive Program of the Brazilian Ministry of Health, without previous prophylaxis, was adopted. After one year, in fluoridated communities the reduction in the incidence of CPOS was of 31.6%, 24.9% and 39.5%, respectively, for the groups aged 6, 8 and 10. In non fluoridated communities the reductions were, respectively, of 24.3%, 26.6% and 27.7%, in every case with statistic significance at the 95% confidence level. Considering the positive results in a developing area, it is recommended that oral health institutions at all levels could adopt a comprehensive and continuous preventive program for children under their responsibility. PMID- 8209161 TI - [Information level and pharmacotherapeutic practice of dentists, 1990]. AB - Results of an investigation carried out into a population of 285 dentists in Cordoba City (Cordoba, Argentine) with a view to evaluating their pharmacological knowledge, prescriptive behaviour and proposals for the improvement of drug usage, are described. This study showed that 58.3% of the dentists surveyed get most of their pharmacological and therapeutic information through published material issued by pharmacochemical labs. At the same time, about one-third of the individuals surveyed either did not answer or gave incorrect answers to questions related to the pharmacotherapeutic effects the antimicrobial or anti inflammatory analgesics of their preference. Although 63.5% of the dentists said that they had taken the essential drug model reference list issued by the social security system into account, many of the drugs selected as preferences were not to be found on it. Regarding anti-microbial or anti-inflammatory analgesic drugs, the brands most frequently prescribed were the more expensive ones, strong 66.5% of the dentists surveyed stated the contrary. Finally, this investigation revealed that five manufacturers together held a concentration of the anti microbial and anti-inflammatory analgesics prescribed by 83.7% and 82.4% of the dentists consulted respectively. PMID- 8209162 TI - [Routine analysis of public health surveillance data: which statistical procedures to use?]. AB - In recent years an increasing interest in epidemiological surveillance (that we prefer to label public health surveillance) has emerged. The viewpoint that the ease of access to computers and statistical software may permit the use of more sophisticated statistical methodologies in the analysis of surveillance data has been profounded in many studies. It is a cause of concern that this attitude, when used indiscriminated by, may lead to analysis lacking in theoretical support. Thus, first, a viewpoint about surveillance in public health is presented and the basic propositions of the theory of statistical hypothesis tests and interval estimation are described briefly and without technicalities. The nature of surveillance data, their nonsampling character and non-random selection are also commented on. Some descriptive procedures that may be used without loss of quality in analysis are described than some procedures that are proposed in the relevant international literature but that need fuller investigation before being introduced in routine data analysis are given. PMID- 8209163 TI - Lyme disease: antibodies against Borrelia burgdorferi in farm workers in Argentina. AB - Lyme Disease is a tick-borne (specially by Ixodes ticks) immune-mediated inflammatory disorder caused by a newly recognize spirochete, Borrelia burgdorferi. Indirect fluorescent antibody (IF) staining methods and enzyme linked immunosorbent assay are frequently relied upon to confirm Lyme borreliosis infections. Although serologic testing for antibodies has limitations, it is still the only practical means of confirming B. burgdorferi infections. Because we have no previous report of Lyme disease in human inhabitants in Argentina, a study was designed as a seroepidemiologic investigation of the immune response to B. burgdorferi in farm workers of Argentina with arthritis symptoms. Three out of 28 sera were positive (#1, 5 and 9). Serum #1 was positive for Immunoglobulin G at dilution 1:320, serum #5 and #9 both to dilution 1:160; while for Immunoglobulin M all (#1, 5 and 9) were positive at low dilution (1:40) using IF. The results showed that antibodies against B. burgdorferi are present in an Argentinian population. Thus caution should be exercised in the clinical interpretation of arthritis until the presence of B. burgdorferi be confirmed by culture in specific media. PMID- 8209164 TI - [A case-control study on the association of hepatitis B virus infection and hepatocellular carcinoma in northern Brazil]. PMID- 8209165 TI - [Aedes (Stegomyia) aegypti L. and associated culicidae fauna in a urban area of southern Brazil]. AB - Some aspects of the ecology of eleven species of Culicidae that were found breeding in recipients in an urban area of Southern Brazil are presented. A great variety of recipients were listed as efficient breeding sites. Apparently Aedes aegypti has been recently introduced into the region and was limited to two areas of the city. Culex quinquefasciatus, Cx. coronator, Ae. aegypti, Ae. fluviatilis e Limatus durhamii were the predominant species. PMID- 8209166 TI - [Intelligence evaluation with short forms of WAIS for populations of low socioeconomic status]. AB - A WAIS-S short form for the assessment of intelligence as a confounding variable is proposed. A number of 161 complete WAIS-S protocols, relating to women of lower-middle and low socioeconomic status were analysed. Six subtests (Social Comprehension, Similarities, Vocabulary, Block Design, Picture Completion and Object Assembly) were chosen using two criteria: specific functions evaluated by each subtest and correlation coefficients relating IQ to the subtests. Five WAIS S short forms were evaluated: one consisting of six subtests and the others with different combinations of four of them. Data showed that they were all appropriate for the measurement of intelligence as a confounding variable; the correlation coefficients between short forms and total IQ ranged from 0.90 to 0.94. The standard errors of the short forms for the estimation of total IQ were of 3 or 4 points, and 3 to 7% of the subjects were wrongly classified. When maternal intelligence had to be measured in relation to infant development the short form that included Social Comprehension, Similarities, Block Design and Picture Completion seemed the most appropriate. Nevertheless when choosing a WAIS S short form not only economy of time but also the specific relevant functions assessed in each subtest must be considered. PMID- 8209167 TI - The social adjustment of patients with schizophrenia: implications to the mental health policy in Brazil. AB - A sample (n = 124) of schizophrenic patients from a defined catchment area of the city os S. Paulo, Brazil, who had been consecutively admitted to hospital, was assessed for psychopathological status and social adjustment levels. Sociodemographic, socio-economic and occupational characteristics were recorded: almost 30% of the subjects had no occupation and received no social benefit, more than two-thirds had a monthly per capita income of US$ 100.00 or less. Sixty-five percent presented with Schneiderian first rank symptoms. Nearly half the sample showed poor or very poor social adjustment in the month prior to admission. The most affected areas of social functioning were participation in the household activities, work and social withdrawal. The current mental health policy of promoting extra-mural care as an alternative to the previous hospital-based model will then mean the investment in a network of new community-based services, that give effective treatment and support to patients and their families. The need of further research into the current picture of mental disorders in the country is stressed. PMID- 8209168 TI - [Traffic accidents in a metropolitan area of southern Brazil--victim and lesion characterization]. AB - Casualties treated in a Emergency Hospital of Porto Alegre, Brazil, during the year 1988, for injuries received as a result of traffic accidents, are described by means of a retrospective study of the data provided by the Documentation and Statistics Sector of the hospital (n = 6.099). The results, similar to those described in the literature, draw special attention to the predominance of the male sex (69.2%), to the concentration of accidents involving individuals of between 20 and 39 years of age, inclusive, (52%) and to the frequency which the head is injured (49.6%) of the patients. Severe injuries such as bruises and fractures were found, respectively, in 61.5% and 24.2% of the patients. The data reveal, further, the large number and the seriousness of the injuries caused by accidents involving pedestrians which accounted for 32.7% of the total number of attendances related to traffic accidents, 57.2% of hospital internments; 54.6% of the victims of this kind of accident were under 9 years of age and 42.8% were over 60. PMID- 8209169 TI - [Arterial hypertension and possible risk factors]. AB - The results of a cross-sectional (prevalence) study of high blood pressure, carried out in 1987 in Araraquara County in the north of S. Paulo State, Brazil are presented. The group studies numbered 1,199 people, including 533 men and 666 women, of from 15 to 74 years of age. The results show a high prevalence of the disease (32.0% for men and 25.3% for women), with a tendency to increase with age, up to the 40's (men) and the 50's (women). There was also a greater percentage of hypertensives in the mulatto and black groups, in the obese, and among those of lower family income, with a lower level of schooling and with less well remunerated jobs. However, the logistic regression showed very small odds ratios associated with these risk factors, which could be attributed to the way these factors were considered. PMID- 8209170 TI - [Diastolic blood pressure associated with accumulated work time among drivers and collectors]. AB - The relationship between diastolic blood pressure and the variables "total cumulative working time" and "age" was examined by regression analysis. The study was carried out among 839 bus drivers and conductors, users of an occupational health center in Campinas, S. Paulo State, Brazil. The main results were a positive association between diastolic blood pressure and cumulative working time, as well as an interaction between this variable and the bus worker's age. PMID- 8209171 TI - [Comparison of two neutralization tests, used in vesiculovirus Piry serodiagnosis]. AB - A serological survey of Piry was undertaken of the sera of inhabitants of Catolancia-Bahia State, Brazil. Serum results obtained by a vesiculovirus neutralization test of C6/36 cells read by ELISA are compared with those obtained by the classic technique, carried out on newborn mice. The agreement between the results was as high as 98.7% of the 204 sera tested and the neutralization test of C6/36 cells was chosen as the most suitable technique for the sero-survey testing. PMID- 8209173 TI - [Occupation and hypertension]. AB - Scientific reports on Arterial Blood Hypertension for the period from 1970 to 1989 are reviewed, with special reference to its epidemiological focusing among workers. The knowledge gained and the theoretical and methodological advances associated with it are assessed. PMID- 8209172 TI - [Canine leishmaniasis in Parana state, southern Brazil]. PMID- 8209174 TI - [Opinions of Brazilian physicians on artificial fertilization from the ethics point of view]. AB - An ethical opinion survey was carried out among Brazilian physicians regarding artificial insemination. The results showed no statistical difference between opinions of physicians from the various regions of the country. PMID- 8209175 TI - Nomenclature of chronic hepatitis: a plea for change. PMID- 8209176 TI - The effect of gastrin-releasing peptide on porcine pancreaticobiliary bicarbonate secretion is mediated by secretin. AB - The effect of gastrin-releasing peptide (GRP) (250, 500, 1000 pmol/kg.h) on the pancreaticobiliary bicarbonate secretion, the pancreatic protein secretion, and the plasma concentrations of secretin and cholecystokinin (CCK) was studied in the anaesthetized pig. Infusion of GRP (1000 pmol/kg.h) increased the portal plasma concentrations of secretin from 0.9 to 13.6 pmol/l and CCK from 1.2 to 38.4 pmol/l, the pancreatic bicarbonate secretion from 0.01 to 5.6 mmol/h, the hepatic bicarbonate secretion from 0.5 to 4.1 mmol/h, and the pancreatic protein secretion from 3 to 680 mg/h. Blocking of CCK-A receptors by MK-329 did not significantly change the effect of GRP, whereas prevention of secretin release by removal of the small intestine caused a 13-fold reduction in the GRP-induced pancreatic bicarbonate secretion and completely abolished the effect on hepatic bicarbonate secretion but did not change the effect on pancreatic protein secretion. We conclude that the effect of GRP on pancreaticobiliary bicarbonate secretion is not mediated through the release of CCK but more likely through the release of secretin and that the effect on pancreatic protein secretion is possibly a direct effect of GRP. PMID- 8209177 TI - Helicobacter pylori gastritis in dyspeptic children. A long-term follow-up after treatment with colloidal bismuth subcitrate and tinidazole. AB - The connection between dyspeptic symptoms and Helicobacter pylori infection was studied prospectively in 21 children treated for verified H. pylori infection with bismuth subcitrate and tinidazole. Gastroscopy with biopsy was performed before and a mean of 4 months after discontinuation of the treatment. A second post-treatment check with determination of H. pylori antibodies and serum pepsinogen 1 level was made a mean of 1.5 years after cessation of treatment. The therapy given cleared the bacteria in 67% of the patients. No significant difference in symptoms was observed between treatment successes and failures. The histopathologic diagnosis of H. pylori infection was accompanied by positive IgG serology in 15 (75%) of the 20 patients tested, and a decrease in antibody levels was observed in children with successful eradication. Serum pepsinogen 1 seemed to be even a better marker in the follow-up. The healing of acute and also to some extent of chronic gastritis took place closely after successful eradication. Our results suggest that healing of H. pylori-induced gastritis should be confirmed at reendoscopy only, independent of the symptoms. PMID- 8209178 TI - Helicobacter pylori infection in north-eastern peninsular Malaysia. Evidence for an unusually low prevalence. AB - The prevalence of Helicobacter pylori infection was determined in peptic ulcer patients, in non-ulcer dyspepsia (NUD) patients, and in the general adult population. The H. pylori infection rate ascertained by microbiologic examination of multiple gastric antral biopsy specimens was 50% (17 of 34) in duodenal ulcer (DU), 5% (1 of 22) in gastric ulcer, and 9% (15 of 159) in NUD patients. A seroepidemiologic survey showed a prevalence of only 4.2% among 496 blood donors and 4.8% among 921 subjects who attended health screening clinics. H. pylori infection is relatively uncommon and does not appear to be the predominant factor in the pathogenesis of peptic ulcer disease in the area. The incidence of peptic ulcer perforations in the area in 1991-92 was 1.5 per 100,000 person-years, reflecting a relatively low frequency of peptic ulcers, which might be due to the low prevalence of H. pylori infection in the population. PMID- 8209179 TI - Cigarette smoke aggravates acid-induced duodenal mucosal injury in the rat. Role of mesenteric vasoconstriction. AB - In anesthetized rats we tested the hypothesis that cigarette smoke potentiates acid-induced duodenal mucosal injury by inducing mesenteric vasoconstriction. Rats inhaled room air or 6 or 12 ml/min cigarette smoke. Study 1: 0.1 N HCl induced duodenal mucosal injury and H+ loss were assessed by histologic evaluation and titration, respectively. Study 2: Superior mesenteric artery blood flow was assessed by pulsed Doppler flowmetry before and during inhalation of cigarette smoke or room air. Twelve milliliter per minute of cigarette smoke aggravated 0.1 N HCl-induced duodenal mucosal injury by significantly increasing the number of villi with deep villous damage. The increased damage was associated with significantly greater loss of H+ from the duodenal lumen. Cigarette smoke produced a dose-related reduction in mesenteric blood flow. We conclude that the vasoconstrictive effect of cigarette smoke on mesenteric blood flow may be involved in the potentiation of acid-induced duodenal mucosal injury. PMID- 8209180 TI - Hyperplastic manifestations of enterochromaffin-like cells in the stomach of rats with congenital moderate hypergastrinemia. AB - The effect of moderate congenital hypergastrinemia on the enterochromaffin-like (ECL) cells was investigated in Zucker rats 4 and 18 months of age by combining autoradiography after tritiated thymidine injection and selective immunocytochemistry. In both age groups the serum gastrin concentration was 200% higher in obese (fa/fa) than in lean (Fa/Fa; Fa/fa) littermates. In 4-month-old obese rats there was a 120% increase (p < 0.05) in the ECL cell labeling index and also a moderate increase in the ECL cell density (p < 0.05) compared with lean controls. In 18-month-old obese rats the hyperplasia was quantitatively more prominent, with both linear and micronodular ECL cell hyperplasia. At this stage, the ECL cell labeling indices in obese and in lean animals were similar. These data support the hypothesis that moderate hypergastrinemia initially accelerates the ECL cell proliferation rate, leading to diffuse ECL cell hyperplasia. In similar conditions, at the latter stage, linear and micronodular ECL cell hyperplasia also develop in most of the hypergastrinemic animals. PMID- 8209181 TI - Site-specific formation of thyrotropin-releasing hormone-induced gastric ulcers through the vagal system. AB - The left and right dorsal motor nuclei (DMN) separately innervate the anterior and posterior gastric walls through the left and right gastric branches of the vagus nerve (GBVN) in rats. The present study was carried out to investigate the effects of selective centrally originated excitation of the unilateral vagal system on the gastric area in which vagus-induced gastric ulcers developed. Since intracisternally injected thyrotropin-releasing hormone (TRH) stimulates neurons in the bilateral DMNs to produce gastric ulcers, selective stimulation of the unilateral vagal system was produced by contralateral gastric branch vagotomy before intracisternal injection of TRH. Intracisternal injection of TRH (2 micrograms/rat) into left gastric branch-vagotomized rats resulted in lesion formation only on the posterior gastric wall and not on the anterior wall. In contrast, in right gastric branch-vagotomized rats TRH-induced gastric lesions were observed only on the anterior gastric wall and not on the posterior wall. These results suggest that selective stimulation of the left or right DMN induces site-specific ulcer formation through the left or right GBVN. Next, gastric acid secretion was determined in pylorus-ligated rats to examine a role of acid hypersecretion in site-specific ulcer formation caused by TRH. Of interest was that gastric acid secretion in unilaterally vagotomized rats given TRH intracisternally was significantly smaller than that in sham-operated rats given intracisternal saline, although the former rats developed gastric ulcers, whereas the latter did not. It is therefore speculated that gastric hyperacidity plays a less important role in the peripheral mechanisms of TRH-induced site-specific gastric ulceration. PMID- 8209182 TI - Highly selective vagotomy in the rat: effects on bone and mineral metabolism. AB - Highly selective vagotomy (HSV) or sham operation was performed in male rats. Fifteen weeks later bone mineralization, fractional intestinal absorption and balance, urinary excretion, and serum levels of calcium, magnesium and phosphorus, together with serum gastrin, parathyroid hormone, calcitonin, vitamin D metabolites, osteocalcin, isoenzymes of alkaline phosphatase, and the urinary excretion of cyclic AMP and hydroxyproline were assessed. HSV induced chronic hypergastrinemia and enhanced the weight of the fundus, antrum, and pancreas. Body weight, food intake, intestinal absorption, mineral balance, and bone mineralization were unaffected by HSV, whereas serum parathyroid hormone levels and urinary hydroxyproline excretion were increased. It is concluded that in the rat 1) HSV has a trophic effect on gastric and extragastric tissues; 2) gastric acid production is not a major determinant of intestinal calcium absorption; and 3) normal bone mass in the presence of signs of hyperparathyroidism indicates an intrinsic capacity of HSV to interfere with calcium metabolism, probably via hypergastrinemia, gastrin being an element of the gastro-parathyroid axis. Our present findings underscore the fact that osteopenia after HSV in man may be a rare finding, but it cannot be ruled out that bone disease found after partial or total gastrectomy may be due in part to concomitant vagotomy. PMID- 8209183 TI - Serum pepsinogens in patients with gastric diseases or after gastric surgery. AB - As no comparative study is available on the categorized serum pepsinogen A and C concentrations, we have measured serum pepsinogens in patients with gastric diseases and after gastric surgery. Hyperpepsinogenemia A (> 120 micrograms/l) occurred frequently in patients with the Zollinger-Ellison syndrome (71%) and hypertrophic gastropathy (100%), whereas hypopepsinogenemia A (< 17 micrograms/l) was found mostly in patients with achlorhydria (87%) and after total gastrectomy (100%). Patients with the Zollinger-Ellison syndrome frequently (58%) had hyperpepsinogenemia C (> 40 micrograms/l), which was also the case in all patients with hypertrophic gastropathy who had in addition a low pepsinogen A:C ratio (< 1.6). Patients with achlorhydria, hypertrophic gastropathy, or after total gastrectomy fell into an aberrant category. From this study we conclude that measurement of serum pepsinogen A and C and calculation of their ratio yield information useful for differentiation of gastric abnormalities. PMID- 8209184 TI - Phospholipase C from Clostridium perfringens stimulates acetyltransferase dependent formation of platelet-activating factor in cultured intestinal epithelial cells (INT 407). AB - The mechanisms by which phospholipase C from Clostridium perfringens stimulates the formation of platelet-activating factor (PAF-acether) in cultured intestinal epithelial cells (INT 407) were investigated. Although stimulation with phospholipase C caused a significant formation of PAF-acether, there was no significant increase in the cellular levels of lysoPAF-acether after stimulation. Moreover, when cells prelabeled with 3H-1-O-alkyl-2-acyl-sn-glycerophosphocholine were stimulated with phospholipase C, the 3H-lysoPAF-acether content was not increased in stimulated cells as compared with unstimulated cells. When cells were preincubated with the calmodulin inhibitor trifluoperazine (TFPA), the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), or the combined phospholipase A2-inhibitor and lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) before stimulation with phospholipase C, the PAF acether formation was significantly decreased. The phospholipase A2 inhibitor 4 bromophenacyl bromide (BPB), on the other hand, had no significant effect on the PAF-acether formation. Preincubation with NDGA also decreased the levels of lysoPAF-acether, whereas BPB, H7, or TFPA had no such effect. These findings indicate that stimulation of acetyltransferase activity with increased acetylation of lysoPAF-acether may be one way by which phospholipase C from C. perfringens stimulates formation of PAF-acether in INT 407 cells. PMID- 8209185 TI - Prevalence and clinical significance of gliadin antibodies in healthy children and adults. AB - Coeliac disease (CD) is associated with the presence of gliadin antibodies (GA) (IgG and IgA), often used as a screening test for CD. Using a modified micro enzyme-linked immunosorbent assay for GA, we studied the prevalence of GA in three healthy groups: children (mean age, 12 years), adult blood donors (mean age, 38 years), and healthy women (mean age, 57 years). We also studied the clinical characteristics of the blood donors. On the basis of findings in 27 untreated CD patients, cut-off levels of IgG and IgA antibody titres were chosen to yield a test with relatively low sensitivity (56%) but high specificity (100%). Analysis of IgM antibodies did not improve the sensitivity. Of the 384 12 year-old children, both IgG and IgA GA positivity was found in 15 (3.91%), a rate significantly greater than that in the blood donors (22 of 1537, 1.43%; p < 0.001) or in the middle-aged women (11 of 944, 1.17%; p < 0.0001). Of the 22 GA positive healthy blood donors, 13 underwent small-bowel biopsy, but only 1 of the specimens manifested histologic changes compatible with CD. The other 12 had normal specimens, including a normal intraepithelial lymphocyte count. The estimated frequency of CD among the blood donors was thus 1 of 1500, a figure consistent with those previously published. We conclude that GA occur frequently in the Swedish population but that their prevalence decreases with increasing age. As a screening test for CD in healthy individuals, the GA titre is of poor predictive value. PMID- 8209186 TI - Faecal DL-lactate concentration in 100 gastrointestinal patients. AB - The relation between faecal DL-lactate and intestinal inflammation or malabsorption was evaluated in 100 nonselected inpatients at a referral center for gastrointestinal disorders. Twenty-one (21%) had DL-lactate concentrations (range, 8-95 mmol/l) above the 95% limit (6.1 mmol/l) in healthy individuals. Inflammatory bowel disease with active proctitis was associated with increased faecal DL-lactate in 11 of 15 patients (73%) (mean, 32 mmol/l; range, 8-95 mmol/l) and in the 1 patient with pouchitis (8 mmol/l), whereas only 1 of 8 patients (13%) with active inflammatory bowel disease without proctitis had L lactate elevation (25 mmol/l). Among 26 patients with malabsorption and quiescent or noninflammatory bowel disease, 3 of 17 (18%) with preserved colonic function and 3 of 9 (33%) with jejunostomy had increased faecal lactate. Only 2 of 50 (4%) patients with neither active inflammatory bowel disease nor malabsorption had faecal DL-lactate elevation. In vitro bacterial fermentation of most dietary polysaccharides did not cause accumulation of lactate, corresponding to a lack of correlation between faecal carbohydrate excretion and lactate accumulation. An isolated increase in faecal L-lactate was observed in 6 of 13 patients with inflammatory bowel disease, whereas D-lactate was not increased without a simultaneous increase of the L-lactate isomer. In conclusion, the faecal lactate concentration was frequently increased in patients with inflammatory bowel disease and proctitis, occasionally increased in patients with severe malabsorption, and often normal in patients with quiescent inflammatory bowel disease or localized Crohn's ileitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209187 TI - Referrals for double-contrast barium examination. Factors influencing the probability of finding polyps or cancer. AB - Predictors of the radiologic detection of colorectal polyps or cancer were studied in 1852 patients referred from primary health care for a double-contrast barium enema. Significant polyp predictors were age 40-79 years (odds ratio (OR), 2.4-5.0) and rectal bleeding (OR, 1.8). Previous colorectal neoplasm, familial history of cancer in general, and male sex were nearly significant predictors of polyps. Significant cancer predictors were age > or = 60 years (OR, 8.6-27.8), rectal bleeding (OR, 2.7), loss of weight (OR, 2.6), and male sex (OR, 2.2). Fatigue and abdominal pain were nearly significant negative predictors for cancer. No association was found between patient delay and the detection of polyps or cancer. Physician delay was significantly shorter in patients with cancer than in cancer-free patients. Age was the most important predictor for the detection of both polyps and cancer, more important than symptoms and history, including family history. PMID- 8209188 TI - A prospective study of first attacks of inflammatory bowel disease and infectious colitis. Clinical findings and early diagnosis. AB - In 105 patients with a first attack of colitis, clinical, microbiologic, laboratory, and histologic features were studied prospectively with the aim of differentiating inflammatory bowel disease (IBD) from infectious colitis as early as possible. Of the patients who proved to have IBD the mode of onset of diarrhoeal symptoms was insidious in 56% and non-insidious in 44%, whereas in 81% of those who proved to have infectious colitis the onset was acute. Most patients with infectious colitis presented within 1 week, had early fever, and did not show histologic features characteristic of IBD. Most IBD patients with a more acute onset had clinical warning signs of IBD such as slight previous bowel symptoms, a late presentation time (> 1 week), and absence of early fever or had histologic features characteristic of IBD. These features were basal plasmacytosis, crypt distortion, more than two vertical crypt branches, villous mucosa, mucosal atrophy, epithelioid granuloma, and Paneth cell metaplasia. Moreover, 61% of the IBD patients with a non-insidious onset fell ill in connection with travelling abroad, gastrointestinal infection, or treatment with antibiotics. Knowledge of the above clinical and histologic factors will facilitate differentiation of IBD from infectious-type colitis. PMID- 8209189 TI - Localization of synaptophysin immunoreactivity in the human liver. AB - The distribution of synaptophysin, specifically located in nerve terminals, was investigated immunohistochemically in normal and diseased human livers in 4 patients with normal liver, 6 with chronic active hepatitis, 12 with cirrhosis, and 8 with hepatocellular carcinoma. In normal liver and chronic hepatitis synaptophysin immunoreactivity was detected in the lobules and portal areas. In cirrhosis it was found in the fibrous septum but in no pseudolobules. Parenchymal innervation would thus appear to cease with the development of cirrhosis, and denervation from the parenchyma may lead to various functional abnormalities in liver cirrhosis. In hepatocellular carcinoma no synaptophysin immunoreactivity was found along carcinomatous sinusoids. Immunoreactive spots were present in the capsules of hepatocellular carcinoma to a much lesser extent than in the fibrous septum of cirrhosis. Neural functions may thus have little effect on the microcirculation of hepatocellular carcinoma. PMID- 8209190 TI - Gallbladder volume in patients with common hepatic duct dilatation. An evaluation of Courvoisier's sign using ultrasonography. AB - To evaluate the usefulness of Courvoisier's sign in ultrasonography, gallbladder size in patients with common hepatic duct dilatation was measured using the ellipsoid method during ultrasonographic examination. During a 6-month period 24 patients with malignant obstructions (6 with carcinoma of the ampulla of Vater, 9 with pancreatic head tumors, 5 with carcinoma of the bile duct, and 4 with malignant lymphadenopathy), 50 patients with calculous obstructions, and a group of 50 normal control patients were examined in this study. Gallbladder volumes were larger in patients with biliary tract dilatation (88.8 +/- 6.8 ml) than in the control group (34.3 +/- 2.8 ml) (p < 0.01). Although the duration and total serum bilirubin level were higher in patients with malignant obstructions, the gallbladder volumes were the same in these two groups (93.0 +/- 11.3 ml versus 86.7 +/- 8.5 ml). A linear relationship was found between gallbladder volume and total serum bilirubin in patients with malignant biliary obstructions (r = 0.6, p < 0.001) and in patients with calculous biliary obstructions without gallbladder stones (r = 0.68, p < 0.001). We hypothesized that the gallbladder volume is irrelevant in differentiating the nature of the biliary tract dilatation and that the gallbladder size is dependent on the degree of biliary obstruction when the gallbladder is not afflicted by fibrosis. PMID- 8209191 TI - Health risk evaluation of nitrogen oxides. Exposure. PMID- 8209192 TI - Absorption and metabolic fate of nitrogen oxides. PMID- 8209193 TI - Toxicity induced by nitrogen dioxide in experimental animals and isolated cell systems. PMID- 8209194 TI - Health risk evaluation of nitrogen oxide. Controlled studies on humans. PMID- 8209195 TI - Experimental studies on nitric oxide. PMID- 8209196 TI - Health risk evaluation of nitrogen oxides. Genotoxicity. PMID- 8209197 TI - Health risk evaluation of nitrogen oxides. Epidemiologic studies. PMID- 8209198 TI - Health risk evaluation of nitrogen oxides. PMID- 8209199 TI - Health risk evaluation and recommended guideline values. PMID- 8209200 TI - Nitrogen oxides in ambient air--properties, sources and concentrations. PMID- 8209201 TI - [Range of neuromuscular involvement in 47 patients infected with the human immunodeficiency virus]. AB - Over a 30 month period, 47 out of 749 patients infected with the human immunodeficiency virus had various neuromuscular symptoms. Based on clinical and electrophysiological data, 47% had distal symmetric polyneuropathy, 11% chronic inflammatory demyelinating polyneuropathy (CIDP), 8.5% toxic neuropathy related to 2-3-dideoxyinosine (DDI), 8.5% cranial neuropathy, 8.5% mononeuropathy multiplex or isolated focal neuropathy, 8.5% progressive lumbosacral polyradiculopathy, and 8.5% myopathy. Half of the patients exhibited previous or concomitant signs of central nervous system involvement and 18 patients died during the study period. CIDP and cranial neuropathies usually appeared early in the course of the disease and consequently showed neurological improvement. Nerve conduction studies of DDI related toxic neuropathies showed distal axono-myelinic sensitivo-motor neuropathy, differing from CIDP by the absence of a conduction block. Distal symmetric polyneuropathies, frequent in the advanced systemic illness, do not systematically require an extended workup, but more unusual peripheral neuropathies which might be treatable necessitate further investigations (electromyography, radiology, serological blood tests; protein chemistry and routine workup of the cerebrospinal fluid). For example, progressive lumbosacral polyradiculopathies responded to early treatment, with a better outcome in one case of herpetic origin than in another case due to cytomegalovirus infection. Our observations suggest that myopathies in HIV infected patients should first be tackled by temporary interruption of virostatic medication, followed by muscle biopsy if the symptoms persist. PMID- 8209202 TI - [Levamisole in children with frequently recurring idiopathic nephrotic syndrome]. AB - 10 children (8 boys and 2 girls) with frequently relapsing idiopathic nephrotic syndrome were treated with levamisole (5 mg/kg weekly). In 6 children with steroid dependent nephrotic syndrome a marked reduction in steroids by 62% to 75% was possible. Severe, transient neutropenia was observed in one patient. Levamisole failed to influence the disease course positively in 3 patients with relapses associated with intercurrent illness. It is concluded that levamisole may favourably influence steroid dependence in children with frequently relapsing idiopathic nephrotic syndrome. PMID- 8209203 TI - [Isolated ACTH deficiency and primary thyroid insufficiency in an atopic patient: hypophysitis?]. AB - 6 years after surgery for epidermoid lung cancer, a 58-year-old man presented with atopic dermatitis and a high level of IgE, primary hypothyroidism of autoimmune origin, slight hyperprolactinemia and adrenal insufficiency of pituitary origin. ACTH levels were low and unresponsive to CRH. There was no deficiency of the other pituitary hormones and the MRI of the pituitary was normal. The other instances of autoimmune thyroiditis associated with ACTH deficiency are reviewed. The etiology of the deficiency is discussed in the context of a possible hypophysitis. PMID- 8209204 TI - [Eosinophilia in primary biliary cirrhosis: regression under therapy with ursodeoxycholic acid]. AB - Eosinophilia can be observed in up to 40% of patients with primary biliary cirrhosis (PBC). Eosinophilia is transient, tends to occur in the early stages of the disease and seems to be associated with episodes of florid bile duct destruction [42-45]. 14 Patients with PBC were examined before and during treatment with ursodeoxycholic acid (UDCA) (10 mg/kg/d) for episodes of eosinophilia and the number of eosinophilic granulocytes in differential white blood cell counts. Group A consisted of 5 patients with one or several episodes of eosinophilia before the start of UDCA. Group B included 9 patients without known episodes of eosinophilia. Observation time before and after start of treatment for group A was 3-96 (mean 25) months and 6-24 (mean 14) months, and for group B 3-108 (mean 34) months and 6-27 (mean 19) months respectively. During treatment with UDCA the mean counts of eosinophilic granulocytes decreased in both groups from 309 +/- 47/mm3 to 135 +/- 14/mm3 (p < 0.001). In group A there was a decrease from 529 +/- 89/mm3 to 157 +/- 17/mm3 (p < 0.001) and in group B from 151 +/- 15/mm3 to 128 +/- 15/mm3 B (n.s.). In group A 9/18 differential white blood cell counts showed eosinophilia before UDCA medication (3 x relative [> or = 6%], 6 x absolute [> or = 500/mm3]) and 0/24 after the onset of UDCA (p < 0.001). In group B 0/25 differential white blood cell counts showed eosinophilia before UDCA and 2/72 after start of the therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209205 TI - [Parietal cell antibodies in primary biliary cirrhosis: pathogenetic or diagnostic significance?]. AB - 24 patients with primary biliary cirrhosis (21 female, 3 male; mean age 51 years) were examined for the occurrence of autoantibodies to gastric parietal cells (APA). APA-titers were correlated with several hematological, chemical and immunological parameters. The results of upper GI-endoscopy were available from 12 patients. APA were positive in 24/24 PBC patients. None of the endoscopies revealed evidence for type A gastritis. No pathological decrease in serum vitamin B12 was found (n = 21). Hemoglobin was either normal (n = 18) or the anemia was microcytic with low serum ferritin (n = 6). Erythrocyte MCV was < or = 97 fl in all patients. No positive correlation was found between APA and erythrocyte sedimentation rate (r = 0.13, n = 24) or the titer of antinuclear antibodies (r = -0.18, n = 24) by linear regression. Correlation coefficient between APA and total serum-Ig was 0.67 (n = 24), 0.74 between APA and serum IgM (n = 24) and 0.13 between total serum-Ig minus IgM (n = 24), indicating that APA found in PBC patients belong to the IgM-isotype. Correlation between APA and anti-M2 was 0.65 (n = 21) and between APA and antimitochondrial antibodies (AMA) 0.96 (n = 24), suggesting recognition of identical epitope(s) by APA and AMA in PBC patients. APA were consistently negative in a control group of 40 patients with various forms of chronic liver disease. We conclude that parietal cell antibodies (APA) in PBC patients seem to be of diagnostic rather than pathogenic importance. Sensitivity for PBC appears comparable to that of AMA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209206 TI - [At the death of Professor Albert A. Buhlmann]. PMID- 8209207 TI - [Are amylases in bakery products and flour potential food allergens?]. AB - The enzyme alpha-amylase from the mould Aspergillus oryzae (Asp o II) routinely used for the production of bread, cakes and pastries has in recent years been identified as an inhalative allergen for occupational diseases (bakers' asthma). It is doubtful whether this amylase in the final product, i.e. after the baking procedure, can still be regarded as an allergen. To clarify this question, detailed case histories on 138 subjects were recorded (98 allergics, 20 patients suffering form chronic intestinal diseases, 20 healthy controls). The clinical examinations included prick skin test and IgE antibody determination using one of the customary enzyme preparations. EAST showed a few of these 138 bread consumers to be weakly sensitized to the enzyme. One of the subjects displayed a significant reaction to alpha-amylase heated to 200 degrees C. As expected, eleven bakers sensitized to alpha-amylase by inhaling it in the workplace (positive prick test, positive case history) predominantly exhibited specific IgE antibodies to the native enzyme. Apart from one weakly positive finding, heated alpha-amylase yielded negative results in this collective. Baking conditions vary widely, especially with regard to single components, temperature and duration. Thus, further investigations as to residual allergenicity or the feasible occurrence of new antigenic determinants during the production of bread, cake and pastries are required. 27% of bakers examined and 9% of atopics showed antibodies to a flour inherent enzyme, a beta-amylase. On the whole, the selected conditions hinted at a weakly sensitizing potential inherent in baking flour and in added amylase. PMID- 8209208 TI - [D-penicillamine-induced myasthenia gravis]. AB - D-penicillamine has been used in the treatment of rheumatoid arthritis for years. As a rare complication of this treatment the occurrence of myasthenia gravis has been described, the clinical features of this complication being indistinguishable from that of idiopathic myasthenia gravis. Both D-penicillamine induced and idiopathic myasthenia gravis show elevated titers of acetylcholine receptor antibodies and respond to acetylcholinesterase inhibitor treatment. We report on a patient with rheumatoid arthritis who, under treatment with D penicillamine, developed severe myasthenia gravis which required temporary acetylcholinesterase inhibitor therapy. 8 months after D-penicillamine was discontinued the acetylcholine receptor antibodies had disappeared and the acetylcholinesterase inhibitors could be withdrawn. Clinical findings and possible pathogenetic aspects of D-penicillamine induced myasthenia gravis are discussed. PMID- 8209209 TI - [Interactions between the nervous and the immune system]. AB - The immune and nervous systems have the capacity to modulate inflammatory processes in an additive, synergistic or antagonistic way. In addition to direct effects, feed-back systems connecting immune and nervous systems exist which provide the basis for a better understanding of the modulation of inflammatory reactions by the central nervous system (nervous as well as neuropsychological influences). It is well established that immunocompetent cells, but also endothelial, epithelial and mesenchymal cells induce and regulate inflammation by production of cytokines. However, the expression, synthesis and secretion of neuropeptides by cells of the immune system or even connective tissue cells has only been recognized recently. These findings indicate that non-neuronal cells in the periphery can feedback to the nervous system by secretion of neuropeptides (e.g. modulation of an afferent signal by interaction of peripherally produced neuropeptides with nerve endings). Nitrogen monoxide has recently been shown to act as an important mediator of inflammatory phenomena and to play an important role in neurotransmission. The rapidly accumulating knowledge of the nature metabolism of this highly reactive substance indicate new therapeutic options in the area of neuroimmunology. PMID- 8209210 TI - [Medical-ethical guidelines for genetic studies in humans. Swiss Academy of Medical Sciences (SAMW)]. PMID- 8209211 TI - [School dental care in danger?]. PMID- 8209212 TI - Condylar rotation and anterior translation in healthy human temporomandibular joints. AB - Mouth opening is achieved by a combined rotatory and translatory movement of the disc-condyle complex within the fossa. The aim of this investigation was to analyse the relationship between condylar rotation and anterior condylar translation during deliberate opening and closing movements. Three consecutive opening and closing movements were recorded by means of the opto-electronic system Jaws-3D in 61 individuals (28 females and 33 males), aged 12 to 76 years, without a past or present history of myoarthropathies of the masticatory system. The computer provided the numeric values as well as the plots of the movement of an intracondylar point in three planes and of the relationship between condylar rotation (opening angle, OA) and anterior translation (AT). The OA/AT curves were also analysed visually for differences in shape. A marked inter- and intraindividual (left/right) variability was found for the ratio between opening angle and anterior condylar translation. Visual analysis of the OA/AT curves allowed them to be classified into five main groups. The groups differed statistically with respect to maximum opening angle and maximum mouth opening. The two groups with a more pronounced rotatory component at the end of opening had a significantly larger mouth opening than most of the other groups. PMID- 8209213 TI - [Color determination in dental ceramics]. AB - Determining the appropriate color of an esthetic restoration is an important step in dental treatment. In this study instead of a shade guide the validity of a recently available objective colorimeter Castor has been investigated. A porcelain-fused-to-metal porcelain (PFM) (Biodent B2), the sinter-porcelain Mark II and the glass-porcelain Dicor have been spectrometrically studied, as well as a Vita shade guide. The Castor equipment has been used for all measurements. The lightness (L*) of the PFM porcelain was not altered by the glaze firing, whereas the red-green-values (a*) tended towards red and the blue-yellow-values towards blue. Total color value (E*) and lightness (L*) of Mark II and Dicor decreased with rising thickness of the samples. At and above a thickness of 1.5 mm, the background had only marginal influence on the L*a*b*-values. It was noticed, that the order by decreasing lightness within the shade guide did not meet official manufacturer declarations, whereas color intensity correlated evidently with the specification. The Castor equipment for color determination is an interesting innovation in dentistry. For the first time and in an economic reasonable frame it permits objective evaluation of color characteristics, such as lightness (L*), red-green (a*) and yellow-blue (b*). PMID- 8209214 TI - Effects of blunt scaling on periodontal status and subgingival microorganisms. A pilot study. AB - Clinical and microbiological effects of 3 periodontal treatments were investigated: (i) scaling and root planing with sharp instruments combined with pocket flushing, (ii) scaling with blunt plastic curettes and pocket flushing, and (iii) pocket flushing alone. Clinically comparable, randomized sites of 8 patients with progressive adult periodontitis were treated 4 times in intervals of approximately 4 months. Prior to each re-treatment and at the end of the study all sites were clinically monitored and the subgingival microflora was examined. Results showed that all treatments were effective in reducing pocket depths and the subgingival microflora, while attachment levels remained unchanged. At individual sites treatment responses were of considerable heterogeneity. In general, clinically improving sites had strongly reduced and sites loosing > or = 3 mm of attachment high residual bacterial cell numbers. Sites with intermediate residual subgingival plaque levels showed quite variable clinical responses. This preliminary study suggests that weakly abrasive procedures could be very valuable for the initial treatment of periodontal lesions. This hypothesis should be further tested in comprehensive clinical trials. PMID- 8209215 TI - [Computed tomography/oral implantology (I). Dental CT: a program for the computed tomographic imaging of the jaws: the principles and exposure technic]. PMID- 8209216 TI - [Case report. Direct transmucosal implants (II): abutment augmentation]. PMID- 8209217 TI - [School dental care: when economies become expensive]. PMID- 8209218 TI - [What happens when school dental care wavers?]. PMID- 8209220 TI - [Video text: dentists are little interested. Survey results: video text as an instrument of internal communication of the SSO. Societe Suisse d'Odonto Stomatologie]. PMID- 8209219 TI - [School dental care: the need for a consensus]. PMID- 8209221 TI - [The etiological mechanisms and diversity of benign thyroid nodules]. PMID- 8209222 TI - [The research project on the Physiopathology of the Oral Mucosa, Molecular Aspects]. PMID- 8209223 TI - Trends in water quality of some wells in Saudi Arabia, 1984-1989. AB - A survey of the quality of 4255 well samples collected from 1062 wells in the period 1984 through 1988, 388 samples collected in 1989, and 319 tank water samples distributed to houses, has been conducted throughout the Kingdom of Saudi Arabia. Sampling included seven regions in Saudi Arabia and analyzed for total dissolved salts, nitrate, nitrite, ammonium and faecal coliforms. The data generally showed a progressive improvement in the quality of well samples during the period under investigation. However, there are still a significant number of water samples showing high levels of pollutants. Nitrate levels of > 45 mg l-1 were observed in 8% of the well samples in 1989 and 5% of them showed the presence of both elevated levels of nitrate and faecal coliforms. Five percent of the well samples in 1989 contained high levels of nitrate, ammonium and faecal coliform. It is concluded that human and animal wastes are the primary continuous source of pollution in the well water samples tested. PMID- 8209224 TI - The gastrointestinal absorption of plutonium and americium in rats and guinea pigs after ingestion of dusts from the former nuclear weapons site at Maralinga: implications for human exposure. AB - The gastrointestinal absorption of plutonium and americium present in dusts from the Maralinga test sites in South Australia has been measured as an input to dose assessments. The materials studied were from three different areas, designated Taranaki (Q380II), TM100 (10/2) and N. Plume (26). The three dusts were fed to groups of rats, mixed with their normal food. The Taranaki and TM100 dusts were also fed to guinea pigs, as a suspension in water. Expressed as fractional absorption from the gastrointestinal tract (f1), the values obtained for plutonium were 2 x 10(-6) and 8 x 10(-6) for Taranaki dust in rats and guinea pigs, respectively, 3 x 10(-6) and 10(-5) for TM100 dust in rats and guinea pigs, respectively, and 2 x 10(-6) for N. Plume dust in rats. The f1 values obtained for americium were 3 x 10(-6) and 2 x 10(-5) for Taranaki dust in rats and guinea pigs, respectively, 10(-5) and 5 x 10(-5) for Taranaki dust in rats and guinea pigs, respectively, and 10(-5) for N. Plume dust in rats. On the basis of these results, rounded f1 values used in the dose assessments were 10(-5) for plutonium and 10(-4) for americium, applying to all intakes of dust. These values compare with the International Commission on Radiological Protection recommendations of 10(-3) for unspecified chemical forms of both elements, 10(-4) for plutonium nitrate and 10(-5) for plutonium oxides. The effect of changes in f1 values on doses from 239Pu and 241Am is considered. PMID- 8209225 TI - Copper, zinc, manganese, iron, lead, cadmium, mercury and arsenic in fish from Lake Tanganyika, Burundi. AB - Atomic absorption spectrometric determination of copper, zinc, manganese, iron, lead, cadmium, mercury and arsenic in two fish species from Lake Tanganyika, Burundi, provide values that are lower than most literature data, especially for cadmium, arsenic and mercury. Tissue analysis of Lates stapersii reveals that liver accumulates the highest amount of most elements. The data illustrates that Lake Tanganyika is still a non-polluted area at the time of analysis. PMID- 8209226 TI - Determination of polychlorinated biphenyl levels in the serum of residents and in the homogenates of seafood from the New Bedford, Massachusetts, area: a comparison of exposure sources through pattern recognition techniques. AB - We measured the residues of polychlorinated biphenyls (PCBs) in the serum of 23 residents of the New Bedford, Massachusetts, area and from two homogenates each of bluefish and lobsters from the same area. We used congener-specific and total Aroclor quantitative approaches, both of which involved gas chromatography with electron capture detection. Using gas chromatography mass spectrometry (electron ionization mode), we confirmed the presence of PCBs in the combined serum samples and in the aliquots of bluefish and lobsters. In measuring the PCB levels in serum, we found good agreement between the two electron capture detector approaches (r > or = 0.97) when the serum of specific congeners was compared to total Aroclor. We used univariate and multivariate quality control approaches to monitor these analyses. Analytical results for bluefish showed a better agreement between the two techniques than did those for lobsters; however, the small number of samples precluded any statistical comparison. We also measured levels of chlorinated pesticides in the serum samples of two groups of New Bedford residents, those with low PCB levels (< 15 ng/ml) and those with high PCB levels (> or = 15 ng/ml). We found that residents with high PCB levels also tended to have higher levels of hexachlorobenzene (HCB) and 1,1-dichloro-2,2-di-(p chlorophenyl) ethylene (p,p'-DDE). The higher concentration of all three analytes appears to be influenced by employment in the capacitor industry, by seafood consumption, or both. Using Jaccard measures of similarity and principal component analysis we compared the gas chromatographic patterns of PCBs found in the serum of New Bedford area residents with high serum PCBs with the patterns found in homogenates of lobsters (inclusive of all edible portions except the roe), in homogenates of bluefish fillets taken from local waters, and in serum from goats fed selected technical Aroclors (e.g. Aroclors 1016, 1242, 1254, or 1260). The patterns found in human serum samples were similar to the patterns found in lobster homogenates. Both of these patterns closely resembled patterns found in the serum samples of the goat fed aroclor 1254, as demonstrated by both pattern recognition techniques. In addition, the chromatographic patterns of human serum and of lobsters and bluefish homogenates all indicated the presence of PCBs more characteristic of Aroclors 1016 or 1242. PMID- 8209227 TI - The concentrations, distribution and sources of cadmium, copper, lead and zinc in the atmosphere of an urban environment. AB - The four metals Cd, Cu, Pb and Zn have been measured in residential city air in a relatively small urban environment. The atmospheric concentrations are Cd, 0.516, 0.305; Cu, 12.5, 8.22; Pb, 155, 70.2; and Zn 47.4, 22.4 ng m-3 at two different sites. Except for lead the concentrations are low and more typical of rural areas in more industrialised centres. The concentrations were found to be higher in the colder and more stable air conditions existing during the winter season. Also concentrations on the flat were higher than those on a hillside probably reflecting the influence of thermal inversions. Wind direction influences the concentrations, they being greater when the wind flow comes across the industrial areas of the city. Some of the major sources of the elements are coal, soil, tyre wear and automobile emissions. PMID- 8209228 TI - Heavy metal contamination in organs of red deer (Cervus elaphus) and wild boar (Sus scrofa) and the effect on some trace elements. AB - In order to determine the contamination level for cadmium (Cd) and lead (Pb) in free ranging red deer (n = 50) and wild boar (n = 118) in 'The Veluwe', a nature reserve in the central part of The Netherlands, concentrations of these metals were measured in liver and kidney. In addition relations between Cd and Pb concentrations and iron (Fe), copper (Cu) and zinc (Zn) concentrations in these organs were studied. The levels of Cd and Pb in wild animals were higher than in farmed animals of the same age, especially in the kidneys. Kidney Cd and Pb concentrations were generally higher than concentrations in liver. However, in wild boar also high Pb concentrations were found. Unlike the kidney there was a saturation in liver Cd accumulation which might be due to an insufficient Cd binding capacity of the liver as the exposure to Cd persisted. There was a strong increase of the kidney Cd concentrations with age in red deer and wild boar, which indicates substantial chronic exposure to this metal. However, concentrations of Cd and Pb were not high enough to be toxic or to affect Fe, Cu, or Zn concentrations in the animal. Compared to other wildlife species in other countries, the kidney Cd concentrations were high in our animals; Pb concentrations in liver and kidney were about the same as Pb concentrations in wildlife in other countries. Because of the high contamination levels of red deer and wild boar from this study it was concluded that De Veluwe is a relatively highly contaminated area, resulting in liver and kidney which are unsuitable for human consumption. PMID- 8209229 TI - Simultaneous multielemental analysis of daily food samples by inductively coupled plasma mass spectrometry. AB - Several toxic elements in total composite food samples of hospital diets were determined simultaneously by inductively coupled plasma mass spectrometry (ICP MS). Trace element concentrations of Be, Cr, As, Cd, Sn, Sb, Ce, Hg and Pb changed widely ranging from a few ng.g-1 to less than 3 micrograms.g-1 in all 24 samples collected through a year. Be, Sn, and Hg were not detected in rice sample alone, and other trace elements, with the exception of Cr and As, were less than approximately 50% levels, as compared with mixed diet samples. The daily intakes of these toxic elements were in the ranges of a few to several hundreds of micrograms. PMID- 8209230 TI - The possible role of selenium in antioxidation in marine waders; a preliminary study. AB - In a marine wader, the oystercatcher (Haematopus ostralegus), the activity of the selenium-dependent enzyme glutathione peroxidase (GSH-Px) in the red blood cells (RBC) was measured. The average activity, 97 +/- 19 units/g Hb, is within the range reported for mammals. No correlation was observed between the selenium concentration and GSH-Px activity in the erythrocytes and it is calculated that only a small percentage of the selenium present in the RBC is bound to the enzyme. Therefore, it is concluded that the high selenium concentrations in the avian red cells cannot be ascribed to GSH-Px. It is argued that a function of selenium in antioxidation is still possible. The positive relationship found between selenium and iron concentrations in the tissues of the oystercatcher directs to such a role. A pitfall in the measurement of GSH-Px activity is outlined. PMID- 8209232 TI - Organochlorine pesticides in Argentinian butter. AB - Organochlorine pesticide residues were analysed in 150 samples of butter collected from several places in the cities of Santa Fe and Rosario (Argentine Republic) over a period of 18 months. Pesticides analysed in butter were: HCH (alpha and gamma isomers), heptachlor and its epoxide, aldrin, dieldrin, and DDT (p,p' DDE, o,p' DDT and p,p' DDT). Most samples contained residues of gamma-HCH (Lindane) and heptachlor (92% and 78%, respectively); alpha-HCH and aldrin were detected in 58% and 55% of samples; dieldrin, heptachlor epoxide, DDT isomers were found in few cases (30%). Mean values of pesticides residues in butter fat were: sigma HCH 0.029 ppm; sigma heptachlor 0.064 ppm; sigma aldrin 0.11 ppm and sigma DDT 0.024 ppm. Residue levels exceeded the limits prescribed by the Food and Agricultural Organization/World Health Organization in only very few cases. PMID- 8209231 TI - Have high selenium concentrations in wading birds their origin in mercury? AB - The relationship between selenium and mercury in marine waders from the Wadden Sea (known to have high tissue selenium concentrations), was investigated in the framework of the possibility that high mercury concentrations may have induced parallel selenium accumulation to detoxify the mercury. The selenium and mercury concentrations are shown to be negatively correlated in both the liver and kidneys of these birds. In the tissues and red blood cells of oystercatchers, positive correlations between the two elements are found. The atom increment Se/Hg ratio in the pooled oystercatcher tissue and red cell data is 32:1. This ratio greatly exceeds the 1:1 ratio found when selenium is accumulated to detoxify mercury. Furthermore, breeding females are able to excrete mercury independently of selenium from the red blood cells, probably into the eggs; the whole egg mercury concentrations of the local breeding populations are low. From these results it is concluded that the high selenium concentrations in waders do not have their origin in elevated levels of mercury. PMID- 8209233 TI - Effect of plumbing systems on lead content of drinking water and contribution to lead body burden. AB - Stable lead isotopes and lead contents in drinking water from a number of Australian cities have been measured to determine the contribution of drinking water to body burden. Lead contents are generally < 2 micrograms/l and thus contribute an insignificant amount to the lead budget in humans in Australia. First-flush and running water samples taken at intervals of up to 10 min show that equilibrium is reached within 1 min or approximately 10 l by volume. There is, however, large variability in both lead content and isotopic composition within the first minute which brings into question the reliability of the recommended sampling time of 30 s. Extremely large isotopic differences between individual dwellings within the one city and between dwellings and the storage tanks for the water supply are attributed to differences in lead residing in the plumbing within the dwellings, usually from lead solder in brass fittings. Isotopic analysis of solder and water from two dwellings confirm this relationship. PMID- 8209234 TI - PCBs and organochlorine pesticide residues in otters (Lutra lutra) and in otter spraints from SW England and their likely impact on populations. AB - PCB and organochlorine pesticide residues were determined in otter (Lutra lutra) spraints (faeces) from nine catchment regions in SW England over the period 1989 1991. Results of analyses of tissues from 22 otters are also presented. Dieldrin occurred in the majority of spraint samples and p,p-DDE and total PCBs in all. Lindane occurred mainly in samples collected in spring. Lindane was not found in otter tissues collected after 1991, but dieldrin, p,p-DDE and PCBs were found in all tissues. Dieldrin and p,p-DDE concentrations were strongly correlated in otter tissues, but there were no correlations with lindane or PCBs. Mean concentrations of contaminants varied widely between catchments. It was considered that PCBs were the compounds of most concern in influencing otter populations and that levels in spraints from one catchment were likely to be sufficiently high to exert a negative effect on populations. While levels of PCBs were elevated above background level in several other catchments and some individual otters had high levels of PCBs, it was considered that they were not sufficient to significantly hinder further population consolidation of otters in SW England. PMID- 8209235 TI - The Environmental Health Profile (EHP) for the Acre Valley (Israel): xenobiotics in animals and physiological evidence of stress. AB - The scope of this study was to analyse the levels of various xenobiotics in animals, wild and domestic, of the Acre Valley in the north of Israel, the most polluted and dense urbanised part of the country. The focus was placed upon the bioaccumulation of heavy metals, such as Pb, Hg, Cu, Zn, Al, Fe, as well as other elements and PCBs. Analysis was also performed on levels of cholinesterase and acetylcholinesterase in birds and man influenced by insecticides in the same region. For this study we used X-ray scanning electron microscopic (S.E.M.) electron probe, atomic absorption spectrophotometry, gas chromatography for PCBs and biochemical methods specific for enzymes. We studied four species of littoral molluscs, four species of birds and five species of mammals including dogs and cats. The results showed very high levels of metals and PCBs and enzyme deviations in birds and man around the sprayed cotton fields, as compared to man from the close to towns. All the collected data will serve as an Environmental Health Profile for immediate and future consideration. PMID- 8209236 TI - Metal content of drinking water supplied to the city of Maracaibo, Venezuela. AB - Total dissolved aluminum, calcium, iron, potassium, magnesium and sodium were evaluated in the drinking water supplied to the city of Maracaibo, Venezuela, to ascertain the water quality for human consumption. Mean concentrations (+/- S.D.) of 533 +/- 313 micrograms/l Al, 32 +/- 4 mg/l Ca, 167 +/- 104 micrograms/l Fe, 2 +/- 1 mg/l K, 5 +/- 2 +/- 1 mg/l K, 5 +/- 1 mg/l Mg and 16 +/- 4 mg/l Na were obtained during a 4-month sampling period that included dry (January-February 1991) and wet (March-April 1991) seasons. Significant seasonal variations (P < 0.002) for aluminium, potassium and magnesium were as follows: 641 +/- 275 and 445 +/- 340 micrograms/l aluminium, 3 +/- 0.5 and 2 +/- 0.5 mg/l potassium and 4 +/- 0.2 and 6 +/- 2 mg/l magnesium for the wet and dry seasons, respectively. The concentration of aluminum was consistently higher than the levels accepted by most international water quality criteria (approximate acceptable value < 300 micrograms/l aluminum), probably because of the inadequate flocculation treatment given to the raw water at the water plant. The rest of the metals under consideration complied with international guidelines of quality criteria for drinking water. The presence of an elevated concentration of humic material (22 +/- 2 mg/l of total organic carbon) in the drinking water should be a matter of public concern. PMID- 8209237 TI - Genetics and behavior. PMID- 8209238 TI - NIH R&D priorities. PMID- 8209239 TI - Risks in using transgenic plants? PMID- 8209240 TI - Electromagnetic fields. Breast cancer link claimed, criticized. PMID- 8209241 TI - AIDS vaccines. Will media reports KO upcoming real-life trials? PMID- 8209242 TI - Mouse model found for ALS. PMID- 8209243 TI - Canine distemper virus. Serengeti's big cats going to the dogs. PMID- 8209244 TI - Flesh-eating bacteria: not new, but still worrisome. PMID- 8209245 TI - Genes and behavior. PMID- 8209246 TI - Behavioral genetics in transition. PMID- 8209247 TI - From fruit flies, rats, mice: evidence of genetic influence. PMID- 8209248 TI - Manic depression. Highs and lows on the research roller coaster. PMID- 8209249 TI - Alcoholism research. A cautionary genetic tale: the sobering story of D2. PMID- 8209250 TI - Genes, environment, and personality. PMID- 8209251 TI - The mating of a fly. AB - Courtship in Drosophila is influenced by a wide variety of genes, in that many different kinds of pleiotropic mutations lead to defective courtship. This may seem to be a truism, but the broad temporal and spatial expression of most of the fly's "neuro genes" makes it difficult to exclude elements of such genes' actions as materially underlying reproductive behavior. "Courtship genes" that seem to play more particular roles were originally identified as sensory, learning, or rhythm mutations; their reproductive abnormalities have been especially informative for revealing components of male or female actions that might otherwise have gone unnoticed. Further behavioral mutations seemed originally to be courtship-specific, turned out not to have that property, and have led to a broadened perspective on the nature and action of Drosophila's sex-determination genes. PMID- 8209252 TI - Genetic animal models of alcohol and drug abuse. AB - Behavioral and pharmacological responses of selectively bred and inbred rodent lines have been analyzed to elucidate many features of drug sensitivity and the adverse effects of drugs, the underlying mechanisms of drug tolerance and dependence, and the motivational states underlying drug reward and aversion. Genetic mapping of quantitative trait loci (QTLs) has been used to identify provisional chromosomal locations of genes influencing such pharmacological responses. Recent advances in transgenic technology, representational difference analysis, and other molecular methods now make feasible the positional cloning of QTLs that influence sensitivity to drugs of abuse. This marks a new period of synthesis in pharmacogenetic research, in which networks of drug-related behaviors, their underlying pharmacological, physiological, and biochemical mechanisms, and particular genomic regions of interest are being identified. PMID- 8209254 TI - The genetic basis of complex human behaviors. AB - Quantitative genetic research has built a strong case for the importance of genetic factors in many complex behavioral disorders and dimensions in the domains of psychopathology, personality, and cognitive abilities. Quantitative genetics can also provide an empirical guide and a conceptual framework for the application of molecular genetics. The success of molecular genetics in elucidating the genetic basis of behavioral disorders has largely relied on a reductionistic one gene, one disorder (OGOD) approach in which a single gene is necessary and sufficient to develop a disorder. In contrast, a quantitative trait loci (QTL) approach involves the search for multiple genes, each of which is neither necessary nor sufficient for the development of a trait. The OGOD and QTL approaches have both advantages and disadvantages for identifying genes that affect complex human behaviors. PMID- 8209255 TI - Higher order self-assembly of vesicles by site-specific binding. AB - The association of lipid molecules into spherical vesicles in solution as a result of non-specific intermolecular forces constitutes a primary self-assembly process. Such vesicles can undergo a secondary self-assembly into higher order structures in a controlled and reversible manner by means of site-specific ligand receptor (biotin-streptavidin) coupling. Cryoelectron microscopy shows these structures to be composed of tethered, rather than adhering, vesicles in their original, unstressed state. In contrast, vesicles aggregated by nonspecific, such as van der Waals, forces are deformed and stressed, producing unstable structures. Vesicle association by site-specific binding provides a practical mechanism for the production of stable, yet controllable, microstructured biomaterials. PMID- 8209253 TI - Forward and reverse genetic approaches to behavior in the mouse. AB - Modern molecular genetic and genomic approaches are revolutionizing the study of behavior in the mouse. "Reverse genetics" (from gene to phenotype) with targeted gene transfer provides a powerful tool to dissect behavior and has been used successfully to study the effects of null mutations in genes implicated in the regulation of long-term potentiation and spatial learning in mice. In addition, "forward genetics" (from phenotype to gene) with high-efficiency mutagenesis in the mouse can uncover unknown genes and has been used to isolate a behavioral mutant of the circadian system. With the recent availability of high-density genetic maps and physical mapping resources, positional cloning of virtually any mutation is now feasible in the mouse. Together, these approaches permit a molecular analysis of both known and previously unknown genes regulating behavior. PMID- 8209256 TI - Attenuation of fungal virulence by synthetic infectious hypovirus transcripts. AB - Noninfectious, cytoplasmically transmissible viral double-stranded RNAs of the genus Hypovirus cause reduced virulence (hypovirulence) in the chestnut blight fungus Cryphonectria parasitica, providing the basis for virus-mediated biological control of a fungal disease. Synthetic transcripts corresponding to a full-length hypovirus RNA coding strand are infectious when introduced into fungal spheroplasts by electroporation. Hypovirus infections were readily established in Cryphonectria parasitica and in related fungal species not previously reported to harbor viruses. These results demonstrate the use of a synthetic mycovirus transcript to expand fungal host range, thereby broadening the potential application of virus-mediated hypovirulence to control fungal pathogenesis. PMID- 8209257 TI - Silencers and domains of generalized repression. AB - Gene expression can be affected by the chromosomal position of the gene. An example of this position effect is silencing of the HML and HMR mating-type loci of Saccharomyces cerevisiae. An in vitro assay revealed that silencing induced a transcription-independent general occlusion of the DNA at HMR from sequence specific interactions of proteins with DNA. The minimum boundaries of the silenced chromatin structure were determined, as were the contributions of the E and I silencers to the size of the silenced domain. Examination of endonuclease sensitive sites provided evidence that neither the integrity of the chromosomal duplex nor covalent linkage of the silencers to HMR was important for maintenance of the silenced structure in vitro. PMID- 8209259 TI - Molecular genetic analyses of the Tyrolean Ice Man. AB - An approximately 5000-year-old mummified human body was recently found in the Tyrolean Alps. The DNA from tissue samples of this Late Neolithic individual, the so-called "Ice Man," has been extracted and analyzed. The number of DNA molecules surviving in the tissue was on the order of 10 genome equivalents per gram of tissue, which meant the only multi-copy sequences could be analyzed. The degradation of the DNA made the enzymatic amplification of mitochondrial DNA fragments of more than 100 to 200 base pairs difficult. One DNA sequence of a hypervariable segment of the mitochondrial control region was determined independently in two different laboratories from internal samples of the body. This sequence showed that the mitochondrial type of the Ice Man fits into the genetic variation of contemporary Europeans and that it was most closely related to mitochondrial types determined from central and northern European populations. PMID- 8209258 TI - Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. AB - Mutations of human Cu,Zn superoxide dismutase (SOD) are found in about 20 percent of patients with familial amyotrophic lateral sclerosis (ALS). Expression of high levels of human SOD containing a substitution of glycine to alanine at position 93--a change that has little effect on enzyme activity--caused motor neuron disease in transgenic mice. The mice became paralyzed in one or more limbs as a result of motor neuron loss from the spinal cord and died by 5 to 6 months of age. The results show that dominant, gain-of-function mutations in SOD contribute to the pathogenesis of familial ALS. PMID- 8209260 TI - Epidemiology and risk factors for head and neck cancer. PMID- 8209261 TI - The role of surgery in head and neck cancer: standard care and new horizons. PMID- 8209262 TI - Radiation therapy in head and neck cancer: indications and limitations. PMID- 8209263 TI - Radiotherapy--new fractionation schemes. PMID- 8209264 TI - Clinical applications of DNA content parameters in patients with squamous cell carcinomas of the head and neck. PMID- 8209265 TI - The role of modern imaging studies in staging and therapy of head and neck neoplasms. PMID- 8209266 TI - Combined modality therapy of head and neck cancer. PMID- 8209267 TI - Rehabilitation of the head and neck cancer patient. PMID- 8209269 TI - Nasopharyngeal carcinoma: the Epstein-Barr virus association. AB - The etiology of NPC is multifactorial and includes virological, genetic, and environmental factors as described. These factors can be synthesized into a model for the development of NPC through a multistep process. First, an individual may carry a genetic predisposed risk of developing NPC as suggested by the HLA linkage of the disease. The nasopharyngeal epithelium becomes infected early in life by EBV and viral gene expression eventually becomes limited to EBNA-1, LMP1, LMP2A/2B, and perhaps another viral protein not yet fully characterized. LMP1 has profound growth stimulating effects in vitro and may exert similar effects in the nasopharyngeal epithelium. As cells are stimulated to divide, the presence of EBNA-1 ensures that the viral genome will replicate and be distributed to progeny cells. Finally, to reach their full malignant potential, the dividing nasopharyngeal cells may acquire cellular genetic changes involving recessive TSGs on chromosome 3. The risk for developing secondary genetic alterations involving these genes may be increased by exposure to environmental carcinogens such as volatile nitrosamines in salted fish. Thus, NPC provides a model system for understanding the interactions of genetic, infectious, and environmental factors involved in oncogenic transformation. Recent developments in organoculture systems and transgenic animal technology should allow dissection at the molecular level of the specific mechanisms involved in this process. PMID- 8209268 TI - Chemoprevention of head and neck cancer. PMID- 8209270 TI - Nasopharyngeal cancer: epidemiology, staging, and treatment. PMID- 8209271 TI - Combination chemotherapy with vinorelbine, ifosfamide, and cisplatin: a phase II study in stage IIIB-IV non-small cell lung cancer. AB - Forty-five stage IIIB-IV non-small cell lung cancer (NSCLC) patients entered a phase II study designed to evaluate the toxicity and the activity of a combination chemotherapy regimen consisting of vinorelbine (25 mg/m2 days 1 and 8), ifosfamide (3 g/m2 day 1 with uroprotective mesna), and cisplatin (80 mg/m2 day 1). The regimen, VIP, was administered on an outpatient basis every 3 weeks. White blood cell counts were checked weekly, and granulocyte colony-stimulating factor was administered in case of grade 4 neutropenia lasting for more than 48 hours. Leukopenia was the most frequent toxicity, with grades 3 and 4 neutropenia reported in 25% of cycles and 11 episodes of febrile neutropenia recorded in 175 evaluable courses. The combination of vinorelbine and cisplatin did not result in additive neurotoxicity: only five patients experienced grade 2 neurotoxicity after six courses of treatment. Thirty-five patients were evaluable for response. Twenty partial responses (57%) and one complete response (2.8%) were observed, for an overall response rate of 60% (95% confidence interval, 42% to 76%). The median time to progression, measured from the start of treatment, was 7 months (range, 1 to 18+), and median survival for the whole group was 12 months (range, 1 to 18+). VIP is a well-tolerated regimen and shows interesting activity in advanced NSCLC. PMID- 8209273 TI - Etoposide/ifosfamide/cisplatin regimens in metastatic non-small cell lung cancer. AB - Although non-small cell lung cancer has long been considered poorly responsive to chemotherapy, there are now a number of chemotherapeutic agents with reproducible activity in this disease, including cisplatin and ifosfamide. Another agent, etoposide, has been rationally incorporated into combination regimens for this disease based on demonstrated preclinical synergy. We review recent studies combining these three agents in the treatment of metastatic non-small cell lung cancer as well as prospects for further development. PMID- 8209272 TI - An ongoing randomized study of neoadjuvant chemotherapy in resectable non-small cell lung cancer. AB - The purpose of this trial is to assess the possible benefit of neoadjuvant chemotherapy before surgery in patients with operable non-small cell lung cancer. Patients with operable stages I (except T 1N0), II, or IIIA disease are eligible for this ongoing trial. Patients are randomized into two arms. Surgery is performed first in group I; patients found to have T3 tumors or N2 lymph nodes are given postoperative radiotherapy. Group 2 patients start with two cycles of chemotherapy; following surgery, two more cycles are administered in responder patients and, as in group I, patients with T3 tumors or N2 lymph nodes are given radiotherapy. Chemotherapy is the MIP protocol: mitomycin 6 mg/m2 day I, ifosfamide 1.5 g/m2 days 1 to 3, cisplatin 30 mg/m2 days I to 3, and mesna 1,200 mg/m2 days 1 to 3. One hundred fifty patients were enrolled between June 1991 and September 1993. By the time this report was prepared, 117 patients had completed all assigned treatment, 63 in group I and 54 in group 2. There were two ineligible patients, one in each group. Forty-nine patients underwent thoracotomy in the chemotherapy-surgery group and 62 in the surgery-only group. There was only one progression after two cycles of chemotherapy. Rates of exploratory and incomplete surgery were 17% in group I and 12% in group 2. The trial is ongoing. PMID- 8209274 TI - A randomized trial of mitomycin/ifosfamide/cisplatin preoperative chemotherapy plus surgery versus surgery alone in stage IIIA non-small cell lung cancer. AB - The efficacy of surgery or radiotherapy as conventional treatment for stage IIIA non-small cell lung cancer (NSCLC) is limited. Recent studies have pointed out that preoperative chemotherapy may improve survival. To reconcile the two approaches, we undertook a multidisciplinary randomized trial to examine the possible synergism between preoperative chemotherapy and surgery in improved survival. Stage IIIA NSCLC patients were randomly assigned to receive either three preoperative courses of mitomycin/ifosfamide/cisplatin chemotherapy and surgery or surgery alone. The median survival was significantly greater in the chemotherapy plus surgery group than in the surgery group (26 months v 8 months; P < .001). However, the prognostic value of the mutated K-ras gene data presented awaits the analysis of larger sample populations. Similarly, the role of high dose cisplatin in inducing higher pathologic complete remissions has to be corroborated in future randomized trials. PMID- 8209275 TI - Trials of radical radiotherapy versus chemotherapy plus radical radiotherapy in non-small cell lung cancer. AB - Currently available treatments for patients with inoperable non-small cell lung cancer have had little impact on long-term survival. Cisplatin-containing chemotherapy regimens have achieved the best response rates (ie, 30% to 50%) in this disease, but trials using these have, for the most part, been too small to detect significant improvements in survival. Two randomized trials have shown a significant impact on survival, including the largest trial published to date (353 cases). Other trials have shown a trend in favor of the combined-modality arm. The only two trials with a trend in favor of radiotherapy alone were those with the smallest number of randomized cases (48 and 65 patients). A meta analysis of trials of cisplatin-containing chemotherapy plus radiotherapy versus radiotherapy alone is thus likely to show a small survival advantage for the combined-modality approach when published in early 1994. In addition, a multicenter trial of mitomycin/ifosfamide/cisplatin (MIC) plus radiotherapy versus radiotherapy alone being performed in the United Kingdom is expected to accrue 500 patients. Preliminary results obtained in 150 patients randomized to receive the combined modality show an objective response rate to chemotherapy of 51%, which supports the findings of the phase 2 study using this regimen. Moreover, both responders and nonresponders to MIC experienced symptomatic improvement (a parameter largely ignored in previous trials) following treatment. Consequently, the MIC trial will be large enough to detect worthwhile survival improvements, should they exist, as well as illustrate the impact of treatment on patients' symptoms. PMID- 8209276 TI - Radiotherapy alone versus chemotherapy with ifosfamide/vindesine followed by radiotherapy in unresectable locally advanced non-small cell lung cancer. AB - In a German multicenter trial, previously untreated patients with unresectable stages IIIA and IIIB non-small cell lung cancer were randomly assigned to receive either radiotherapy alone (arm A) or chemotherapy followed by radiotherapy (arm B). Chemotherapy in arm B consisted of ifosfamide 1,500 mg/m2 intravenously on days 1 to 5 and 29 to 33, and vindesine 3 mg/m2 intravenously on days 1 and 5 and 29 and 33. Radiotherapy started on day 1 in arm A and on day 56 in arm B. Single doses of 2 Gy were given 5 days a week for 3 weeks and after a 2-week interval for an additional 2 weeks. The total radiation dose was 50 Gy. Concurrent to radiotherapy, cisplatin was given as a radiosensitizer at a dose of 20 mg/m2 once a week. From July 1986 to March 1989, 85 patients were randomized, of whom 78 were evaluable. Main prognostic factors were well balanced. Of the patients receiving chemotherapy, 25% had a partial remission after two cycles, 46% showed no change, and 29% had progressive disease. After radiotherapy, response rates were 49% in arm A and 58% in arm B, including a 10% complete remission rate in both groups. After two thirds of the projected sample size had been included, an analysis of survival was performed and showed a statistically significant advantage for the treatment group including chemotherapy (P = .016). Median survival was 9.0 months versus 13.7 months and 2-year survival was 12% versus 24%, both in favor of the group receiving chemotherapy. These results caused premature discontinuation of patient accrual according to the study protocol and the recommendations of the Ethics Review Board of the Philipps-University Hospital. The results of this trial indicate that chemotherapy is able to prolong survival of patients with locally advanced unresectable non-small cell lung cancer and should be considered for treatment of these patients. PMID- 8209277 TI - Future directions in the treatment of non-small cell lung cancer. AB - Lung cancer is now the leading cause of cancer-related mortality for both men and women in North America. Non-small cell lung cancer (NSCLC) accounts for 75% to 80% of all primary lung tumors. Although the survival rate for patients with NSCLC remains poor, recent advances in our knowledge of the pathophysiology and biology of lung cancer have paved the way for the development of new, more effective therapeutic interventions. This paper reviews the current status and future prospects for the management of NSCLC, including adjuvant therapy following surgical resection for stages I, II, and IIIA disease; induction chemotherapy for locally advanced stages IIIA and IIIB disease; chemotherapy for advanced stage IV disease; and biologic response modifiers, including interferons, interleukins, colony-stimulating factors, and monoclonal antibodies. PMID- 8209278 TI - Dose-intensive ifosfamide/carboplatin/etoposide plus granulocyte-macrophage colony-stimulating factor for non-small cell lung cancer. AB - Whereas non-small cell lung cancer (NSCLC) comprises 80% of all lung cancer cases, effective prolongation of survival in NSCLC patients using currently available combination chemotherapy has been problematic. Use of dose-intensive chemotherapy along with hematopoietic growth factor support is an attractive, albeit experimental, alternative. We have conducted a phase I study to determine the maximum tolerated dose of etoposide in the ifosfamide/carboplatin/etoposide (ICE) regimen when used with granulocyte-macrophage colony-stimulating factor (GM CSF) support. Twenty-three patients with solid tumors refractory to standard treatment who had not received previous platinum-containing chemotherapy or for whom there was no generally accepted curative therapy were treated. We present results obtained in 11 patients with previously untreated stage IV NSCLC. The use of ICE plus GM-CSF demonstrated promising activity in this group of patients; the overall response rate was 64%, and median survival was 10.0 months. The maximum tolerated dose of this regimen is 900 mg/m2 etoposide in combination with 5 g/m2 ifosfamide, 400 mg/m2 carboplatin, and 5 micrograms/kg/d GM-CSF. PMID- 8209279 TI - Current topics in neonatology. Proceedings of a meeting dedicated to Professor Bent Fris-Hansen. Chatham Bars, Massachusetts, July 1993. PMID- 8209280 TI - Postnatal solid accretion in preterm infants is similar to that reported in utero, but may be overestimated by energy balance techniques. PMID- 8209281 TI - Influence of antenatal betamethasone and gender cohabitation on outcome of twin pregnancies 24 to 34 weeks of gestation. PMID- 8209283 TI - Sources of carbon monoxide (CO) in biological systems and applications of CO detection technologies. AB - Carbon monoxide is produced from a variety of sources in biological systems. Heme oxygenase and heme oxygenase-like activity is the predominant source in mammals, and may be equally important in plants and lower animals. The enzyme appears to be ubiquitous, highly conserved throughout phylogeny, and tightly regulated during development. This and other evidence suggests that heme oxygenase has an important physiological role, of which CO production may be a part. Other minor sources of CO include the oxidation of organic molecules. This includes the following: (1) auto-oxidation of phenols, flavenoids, and halomethanes; (2) photo oxidation of organic compounds; and (3) lipid peroxidation of membrane lipids. No longer thought of as a waste product only, recent studies suggest that in the central nervous system cellular CO production can influence cGMP levels through effects on soluble guanylyl cyclase activity. Cellular CO production may also be linked to cell-cell interactions, and may be important in the cell's response to environmental changes. Whether CO will have a place similar to nitric oxide in cellular metabolism is still unclear, but it is apparent that these metabolic relationships will become increasingly complex. Cellular heme oxygenase activity results in the equimolar production of CO and bilirubin for each molecule of heme degraded. The CO thus formed diffuses into the blood, is carried via hemoglobin, and is excreted in the lungs. Therefore, CO production can be assessed clinically by measuring the rate of total body CO excretion, blood COHb levels, and end tidal CO concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209282 TI - A model of the effect of surfactant treatment on gas exchange in hyaline membrane disease. PMID- 8209284 TI - Deficiency in prostaglandin E2 (PGE2) receptors, mainly EP2 subtype, on brain synaptosomes in early development: implications on cerebral metabolism. PMID- 8209285 TI - Ethical decision-making and neonatal resuscitation. PMID- 8209286 TI - The impact of hate violence on victims: emotional and behavioral responses to attacks. AB - Criminal acts stemming from prejudice based on race, religion, sexual orientation, or ethnicity--frequently referred to as "hate violence"--have increased during recent years. This study explored the nature of hate attacks and victims' responses to them. The sample consisted of 59 victims and included black, white, and Southeast Asian people. Data were obtained through focus group meetings, individual interviews, and questionnaires. More than half of the victims reported experiencing a series of attacks rather than a single attack. Anger, fear, and sadness were the emotional responses most frequently reported by victims. About one-third of the victims reported behavioral responses such as moving from the neighborhood or purchasing a gun. The responses of hate violence victims were similar to those of victims of other types of personal crime. Implications for social work intervention are discussed. PMID- 8209287 TI - Asian and Pacific Island elders: issues for social work practice and education. AB - The highly diverse Asian and Pacific Island population in the United States doubled in size from 1980 to 1990 and is now the nation's fastest-growing minority group. This article describes the Asian and Pacific Island elderly population and its ethnic diversity, geographic location, gender ratios, income and poverty, health status, service utilization, and cultural values and beliefs. Also presented are the specific challenges for social workers in practice settings in designing and providing culturally relevant services and programs. A number of suggestions for social work education to meet the needs of this growing aging population are offered, including the development of an ethnogerontological and multicultural social work curriculum and the critical need for data on this population. PMID- 8209288 TI - Assessing client strengths: clinical assessment for client empowerment. AB - The proposition that client strengths are central to the helping relationship is simple enough and seems uncontroversial as an important component of practice. Yet deficit, disease, and dysfunction metaphors are deeply rooted in clinical social work, and the emphasis of assessment has continued to be diagnosing abnormal and pathological conditions. This article argues that assessment in clinical practice, among other things, is a political activity. Assessment that focuses on deficits provides obstacles to client exercise of personal and social power and reinforces those social structures that generate and regulate unequal power relationships that victimize clients. Clinical practice based on metaphors of client strengths is also political in that it is congruent with the potential for client empowerment. This article discusses the importance of a client strengths perspective for assessment and proposes 12 practice guidelines that foster a strengths perspective. PMID- 8209289 TI - Psychiatric social work and socialism: problems and potential in China. AB - At present social work is almost unheard of in China. Grassroots responses to the needs of mentally ill people and their families, based on the use of untrained officials and volunteers, are insufficient. In some cases, intervention may be unwelcome because of the stigma that surrounds mental illness in China and the families' desire to keep the matter private. The problems and difficulties- practical, emotional, and social--that families and patients face are not dissimilar to those of their counterparts in the West. Doctors and nurses adopt a biological explanatory model and show little interest in the wider environment of the patient, even when environmental factors can be clearly demonstrated to impinge on the illness. The authors conclude that there is a role and a need for social workers in psychiatric settings in China. Although this would undoubtedly be social work with Chinese characteristics, it would be recognizable as consistent with professional social work practice elsewhere. PMID- 8209290 TI - The challenge of racial difference: skills for clinical practice. AB - Just as racial injustice negatively affects the plight of minorities in society, racial tensions impede professional helping. Often, the racially dissimilar social worker and client approach each other with little understanding of each other's social realities and with unfounded assumptions. Unfortunately, professionals find it difficult to acknowledge such differences or their effect on their relationships. Yet the fruitfulness of the helping encounter often depends on the ability to develop and invest in a trusting relationship. This article identifies the societal roots of the stresses associated with cross racial relationships. Three concerns commonly experienced by clients whose workers are racially different are identified: (1) Is the helper a person of goodwill? (2) Is the helper trained and skilled? (3) Is the help offered valid and meaningful for me and my social reality? Case vignettes are used to illustrate how each concern is typically mishandled. The importance of successfully managing each concern is stressed, and skills for successful management are illustrated. PMID- 8209292 TI - Out of the closet: readers respond. PMID- 8209291 TI - Posttraumatic stress disorder or midlife crisis in Vietnam veterans? PMID- 8209293 TI - Laparoscopic cholecystectomy and the common bile duct. PMID- 8209294 TI - Intraperitoneal mesh--a word of caution. PMID- 8209295 TI - Intravenous cholangiography, ERCP, and selective operative cholangiography in the performance of laparoscopic cholecystectomy. AB - Between March 1990 and March 1993 some 822 consecutive patients underwent an attempt at laparoscopic cholecystectomy. Intravenous cholangiography (IVC), ERCP, and selective intraoperative cholangiography (IOC) were used in the evaluation of common bile duct (CBD) stones. Two hundred thirteen patients (26%) were identified preoperatively with either abnormal liver functions or a dilated common bile duct suggestive of CBD stones. IVC was performed in 143 patients (67%). Choledocholithiasis was identified in 14 patients (10%). Preoperative therapeutic ERCP was successful in all 14 patients (100%). Diagnostic ERCP was attempted in 61 patients and successful in 59 (97%). Choledocholithiasis was identified in 25 patients (41%). Successful extraction was accomplished in 23 patients (92%). Transcystic common bile duct exploration was used effectively in the patients with an unsuccessful ERCP. IOC was attempted in 50 patients and successful in 48 (96%). Choledocholithiasis was identified in three (6%). A retained CBD stone was present in eight patients (1%). There was one level I CBD injury (0.122%). The use of IVC, selective ERCP, and selective IOC is a reasonable approach in the performance of laparoscopic cholecystectomy. PMID- 8209296 TI - Laparoscopic cholecystectomy with operative cholangiogram. AB - Intraoperative cholangiography was successfully performed in 99% of 525 consecutive laparoscopic cholecystectomies. There were 386 chronic, 54 acute, 44 fibrotic, 19 gangrenous, and 22 hydrops cases. Unsuspected common duct stones were identified in 5% of patients. Routine cholangiography to clarify the biliary anatomy, however, was of greater significance than the discovery of unsuspected common duct stones. PMID- 8209297 TI - The utility of laparoscopic common bile duct exploration in the treatment of choledocholithiasis. AB - Laparoscopic common bile duct exploration (CBDE) was performed in 24 patients over a 23-month period. Fourteen of these patients were suspected preoperatively of harboring common bile duct (CBD) calculi. Of these, endoscopic sphincterotomy was unsuccessful in eight. Laparoscopic CBDE was performed either transcystically or via a choledochotomy. In all cases, completion cholangiography demonstrated that the CBD was free of stones. All patients were sent home with drains placed in their extrahepatic biliary system. Mean hospital stay was 2.7 days. There was no mortality. The overall morbidity rate was 29.1%. It included one trocar site infection (4.1%), four cases of mild postoperative amylasemia (16.6%), and two cases of retained stones (8.3%) seen in two patients on follow-up tube cholangiography that were successfully extracted percutaneously. The authors feel that laparoscopic CBDE is a safe and effective method of CBD stone removal that offers an alternative to preoperative ERCP and sphincterotomy. PMID- 8209298 TI - Cholecystocholangiography vs cystic duct cholangiography during laparoscopic cholecystectomy. A prospective controlled trial. AB - Intraoperative cholangiography performed during laparoscopic cholecystectomy provides an exact picture of the biliary anatomy. It may prevent iatrogenic bile duct injury and detect unsuspected common duct stones. Laparoscopic cannulation of the cystic duct can be difficult and time-consuming. We therefore evaluated the simpler technique of cholecystocholangiography by direct puncture and filling of the gallbladder with contrast medium. This technique was compared with cystic duct cholangiography in a prospective controlled trial of 69 patients. Cystic duct cholangiography (n = 38) showed significantly better results than cholecystocholangiography (n = 31) with optimal visualization of the biliary tree in 29 cases (76%) and seven cases (22%), respectively. The failure rate was 8% and 52%, respectively. Delineation of the cystic duct junction is important in order to prevent bile duct injury. The anatomy in this region was clearly delineated in 34 cases (89.5%) using cystic duct cholangiography but only in 11 cases (35.5%) with cholecystocholangiography. Cystic duct cholangiography revealed unsuspected common duct stones in three cases; however, choledocholithiasis was missed by cholecystocholangiography in at least two patients. Cystic duct cholangiography is clearly the optimal technique. In situations of unclear anatomy in which safe dissection of the cystic duct is not possible, cholecystocholangiography remains a useful alternative. PMID- 8209299 TI - Intraoperative cholangiography during laparoscopic cholecystectomy. Routine vs selective policy. AB - An audit of routine intraoperative cholangiography in a consecutive series of 496 patients undergoing laparoscopic cholecystectomy has been performed. Cannulation of the cystic duct was possible in 483 patients (97%). The use of portable, digitized C-arm fluorocholangiography was vastly superior to the employment of a mobile x-ray machine and static films in terms of reduced time to carry out the procedure and total abolition of unsatisfactory radiological exposure of the biliary tract. Repeat of the procedure was necessary in 22% of cases when the mobile x-ray equipment was used. Aside from the detection of unsuspected stones in 18 patients (3.9%), routine intraoperative cholangiography identified four patients (0.8%) whose management would undoubtedly have been disadvantaged if intraoperative cholangiography had not been performed. PMID- 8209300 TI - The Mexican experience with laparoscopic cholecystectomy and common bile duct exploration. A multicentric trial. AB - We present here the initial data collected since the first laparoscopic cholecystectomy (LC) was performed in our country (June 1990). Twenty-one centers were surveyed (2,399 patients). The most frequent indication for LC was chronic gallstone disease (76.2%). The female population predominated (69.4%). Seven centers always perform the laparoscopic approach. Antibiotic prophylaxis is the rule, and most centers use nasogastric tube and urinary catheterization. Perioperative cholangiography is done selectively. The instrument of choice to dissect the gallbladder is the electrosurgical hook-knife. General anesthesia is preferred (97%). The complication rate was 8.87%. Injury to the bile duct and bowel perforation occurred in 0.25% and common duct stone retention occurred in 0.29% of patients. Mortality rate reached 0.12%. It is our hope that this study will help in defining the situation of LC in developing countries and that it also can serve as a first step in the organization of minimally invasive surgery groups in Mexico. PMID- 8209301 TI - Laparoscopic transcystic choledochoscopy. AB - Preoperative prediction of common bile duct stones (CBDS) is imprecise. Cholangiography during laparoscopic cholecystectomy (LC) is the best method for detection of CBDS. Treatment of most stones detected at LC can be safely accomplished using transcystic choledochoscopy and stone extraction. This technique is applicable in nearly 90% of patients with CBD calculi. It may be preferable to endoscopic sphincterotomy (ES) in younger patients and is probably equivalent to ES in patients over 65 years of age. PMID- 8209303 TI - Hemodynamic effects of argon pneumoperitoneum. PMID- 8209302 TI - Hemodynamic effects of argon pneumoperitoneum. AB - The hemodynamic effects of argon pneumoperitoneum were studied to define its possible role as an alternative gas for intraperitoneal insufflation during minimally invasive surgery. Adult pigs were anesthetized and placed on mechanical ventilation. Parameters measured or determined included mean arterial (MAP), pulmonary arterial (PAP), pulmonary arterial wedge (PAWP), right atrial (CVP), and inferior vena cava venous (IVC) pressures, total excretion of CO2 (VCO2), oxygen consumption (VO2), minute ventilation, and arterial blood gases. Also determined were cardiac output, stroke volume, and systemic vascular resistance all indexed to weight (CI, SVI, SVRI). Data were recorded during a 1-h baseline, 2 h of insufflation with argon gas at a constant pressure of 15 mmHg, and 1 h recovery after desufflation. There was no significant change from baseline in VCO2, VO2, MAP, PAP, PAWP, CVP, PaCO2, or arterial pH. Argon pneumoperitoneum significantly increased systemic vascular resistance index and exerted a depressant effect on stroke volume index and cardiac index by 25% and 30% from baseline values, respectively (P < 0.05). Inferior vena cava pressure increased as a reflection of the intraabdominal pressure. Argon insufflation had no effect on respiratory function. Argon gas may not be physiologically inert, and in patients with cardiovascular disease its effects may be clinically important. PMID- 8209304 TI - Childhood abdominal tuberculosis. The role of echo-guided fine-needle aspiration in its management. AB - Two children presented with abdominal tuberculosis. Because of the nonspecific clinical features, the diagnosis required a high index of clinical suspicion. Fine-needle aspiration (FNA) under ultrasonographic guidance allowed an early definitive diagnosis and bacteriological confirmation to guide chemotherapy. Both patients responded well to antituberculous chemotherapy. PMID- 8209305 TI - Rare bile duct anomalies. A case report and implications for laparoscopic cholecystectomy. AB - Anomalies of the biliary ductal system are not uncommon, and are of variable clinical significance. A case is reported of an extremely unusual variation, with the cystic duct entering the left hepatic duct. Preoperative delineation of the anomaly in this patient by endoscopic retrograde cholangiography assisted in the subsequent performance of a safe laparoscopic cholecystectomy. Awareness of potential biliary variations is one factor in avoidance of ductal injuries during laparoscopic surgery. PMID- 8209307 TI - Considerations in laparoscopic surgery for acute cholecystitis. PMID- 8209306 TI - Combined use of laparoscopy and endoscopy in diagnosing and treating Dieulafoy's vascular malformations of the stomach. AB - We present the case of a 70-year-old female successfully treated for a bleeding Dieulafoy's gastric lesion with a combined laparoscopic/endoscopic approach. An increasing percentage of surgery is now being performed laparoscopically and the authors feel that combined laparoscopic/endoscopic surgery offers advantages to the patient over either of these methods individually and over open surgery. This report demonstrates that a bleeding point anywhere on the gastric wall is amenable to laparoscopic intervention if the localization techniques we describe are utilized. PMID- 8209308 TI - Response to invited commentary on SAGES study. PMID- 8209309 TI - [Telemedicine. A discipline without limits and possibly an educational revolution of the 1990's]. PMID- 8209310 TI - [Female circumcision--a genital mutilation]. PMID- 8209311 TI - [Paracetamol]. PMID- 8209312 TI - [Paracetamol--kidney and urinary tract. A cause of analgetic nephropathy or cancer?]. AB - In Norway, the total consumption of non-opioid analgesics has not changed during the last ten years and was 36 defined daily doses/1,000 inhabitants/day in 1992. However, there has been a clear switch from acetyl-Salicylic acid (ASA) to paracetamol during this period. The consumption of phenazone is relatively high. Phenacetin consumption has never been a problem, and out of 3,000 renal transplanted patients at Rikshospitalet, Oslo, during the last 25 years less than 1% suffered analgesic nephropathy. It is beyond doubt that phenacetin, when taken together with either ASA or phenazone, increases the risk of urothelial cancer, especially of the renal pelvis and ureter in humans. The dramatic reduction in the incidence of analgesic nephropathy after the sale of phenacetin was prohibited has not been paralleled by a decrease in kidney or urothelial cancer. The human carcinogenicity data for paracetamol in the kidney and urinary tract is discussed. Clinical and epidemiological data, including several population based case-control studies, provide inadequate evidence of any carcinogenicity of paracetamol in the kidney or urinary tract in humans. However, chronic use of high doses of paracetamol should be avoided, probably also consumption of paracetamol in combination with ASA. PMID- 8209313 TI - [Tele-echocardiography. Education in echocardiography via video conferences]. AB - This paper evaluates instruction via video conferences in the training of a physician previously inexperienced in echocardiography, and the diagnostic precision of this method. An inexperienced doctor performed the investigations in 38 patients at a local hospital and the ultrasound signals were transferred to a referral hospital 900 km away where a cardiologist served as instructor. The instructor was blinded to all patient identifications and later examined the patients directly. M-mode, two dimensional echo and Doppler data were assessed. There was a difference of possible clinical importance in only two patients in the two-dimensional assessment, and in one patient in the quantification of mitral regurgitation. For the M-mode measurements, the differences observed were comparable to the results of other investigators, for the Doppler measurements they were slightly larger. Except for a left ventricular aneurysm in one patient, no diagnoses of clinical importance were missed. Our experience is that teleechocardiography is a method that is suitable for basic training in echocardiography, and that the diagnostic precision is sufficient for the method to be applied clinically. PMID- 8209314 TI - [Diagnoses in medical and surgical patients. Experiences of a junior physician]. AB - This article presents the diagnoses of 1,078 patients treated during one year of internship in a local hospital in western Norway. The patients were seen in the surgical outpatient clinic or when admitted to the medical, surgical or pediatric departments. In the surgical outpatient clinic the patients usually attended for treatment of fractures, distortion traumas or traumas without fractures. The most common diagnoses in the medical department were related to acute ischaemic heart conditions, whereas the majority of the patients received in the surgical department had acute abdominal pain. Infectious diseases were the most common cause of hospitalization of children. Information about the different diagnosis encountered during work in a local hospital may be of value to others who are preparing to work in similar institutions. Such an internship may provide valuable experience in the diagnosis and treatment of the most common somatic diseases. PMID- 8209315 TI - [Teratoma of the medullary cone as a cause of peripheral polyneuropathy]. AB - This paper describes a 45 year-old man who had a teratoma in the conus medullaris. The symptoms started about 20 years earlier, and for several years consisted of peripheral motor and sensory signs. Therefore the disease was interpreted as a motor and sensory neuropathy. The tumour was diagnosed by magnetic resonance imaging. Histological examination revealed respiratory epithelium with connective tissue and fat. PMID- 8209316 TI - [Physical inactivity of adults with functional disabilities and diseases]. AB - This article describes physical inactivity among adults in Nord-Trondelag who suffer from or have suffered from heart infarction, angina pectoris, stroke, impaired motor ability, impaired vision, impaired hearing or impairment because of psychological complications. Information was collected by questionnaire during the Nord-Trondelag Health Survey 1984-86. Younger men and younger women with previous heart infarction reported less inactivity than persons with no history of infarction. In contrast, young men and women suffering from impaired hearing were more inactive than people not suffering from impaired hearing. Among the disabled or sick, more women reported physical inactivity than men. This also held good when the results were controlled for age. Among healthy persons, the highest share of physically inactive was found in the oldest age groups, regardless of gender. This survey indicates that, to some degree, physical activity has become an accepted means of improving health after heart infarction in younger men and women. Physical activity has unexploited potential as a means of treating other disabilities and illness. PMID- 8209317 TI - [Complications of acupuncture therapy. A study of the literature from 1981-92]. AB - This study presents the adverse affects of acupuncture as recorded in the Medline database for the years 1981-92. Pneumothorax is the most common mechanical organ injury caused, while hepatitis dominates the infections. Neither pneumothorax nor hepatitis is reported from any Nordic country. Most of the adverse effects of acupuncture seem to be associated with insufficient basic medical knowledge, a low standard of hygiene and inadequate education in acupuncture. The study confirms adverse effects of acupuncture in certain circumstances. Serious adverse effects are few, and acupuncture can be considered as a fairly harmless form of treatment. PMID- 8209318 TI - [Can processes connected to muscular activity explain development of chronic pain?]. AB - The pathogenetic mechanisms of chronic muscle pain are not known, but may be related to incomplete recovery between bouts of work. During monotonous repetitive static muscle contraction, fatigue develops gradually, parallel to an increase in oxidative metabolism combined with a change in Ca(2+)-homeostasis in a few muscle fibres. Ischemia or high lactate probably do not contribute to fatigue in this state. We review some recent results on muscle fatigue during a low force static work situation and also discuss the significance of K+ released from muscle as an important extracellular messenger. PMID- 8209319 TI - [Treatment of paracetamol poisoning. An indication for liver transplantation?]. AB - Development of metabolic acidosis (pH < 7.30) or the combination of encephalopathy grade III-IV, coagulopathy (PT > 100s) and oliguric renal failure are associated with a poor prognosis in paracetamol-induced fulminant liver failure. It is important to administer N-acetylcysteine as soon as possible after the overdose, but N-acetyl-cysteine also seems to improve survival when given 36 80h following ingestion. Liver transplantation has been performed in some patients with paracetamol-induced fulminant liver failure, but convincing evidence that transplantation improves survival in this group of patients is still lacking. We discuss the difficulties met in deciding if and when to perform liver transplantation. Renal failure may develop some days after paracetamol poisoning, even in the absence of severe liver damage, and haemofiltration and haemodialysis may be necessary. PMID- 8209320 TI - [DNA damages caused by paracetamol]. AB - Studies on cells in vitro and animal experiments show that paracetamol may bind covalently to DNA, inhibit DNA-replication and DNA-repair synthesis, and cause chromosomal aberrations in somatic cells. In two studies a higher level of chromosomal aberrations was found in lymphocytes after exposure of human volunteers to therapeutic doses of paracetamol, but in a third study the results were negative. Genotoxic effects of paracetamol have been demonstrated both in vitro and in vivo at or near therapeutic concentrations. Overall, the data indicate that paracetamol-use may contribute to an increase in the total burden of DNA-damage in man. Higher risk of cancer after exposure to paracetamol has not been demonstrated in epidemiological studies, nor has increased risk of cancer been unequivocally documented from animal experiments. It is generally accepted, however, that exposure that may cause DNA-damage in man should be reduced and if possible avoided. The therapeutic benefit of using paracetamol should therefore be carefully evaluated, taking into consideration its potential for inducing acute and chronic and genotoxic effects. PMID- 8209321 TI - [Month of birth and prevalence of fibromyalgia]. AB - We have studied the possible influence of season of birth on prevalence of fibromyalgia. Data from the Norwegian Fibromyalgia Association, where diagnosis is compulsory, were compared with mean figures for 1936-65 from the National Register of Births. Figures for 8,125 patients were correlated with figures for two million persons from the register. Unlike other musculoskeletal diseases, which are more prevalent in summerborn persons, and certain mental diseases, which are more prevalent in winterborn persons, no such association was found for fibromyalgia. PMID- 8209322 TI - ["The patient slipped on the ice...". Non-traffic related fractures among pedestrians, occurrence and seasonal variations]. AB - The epidemiology of non-traffic-related fractures among pedestrians in three Norwegian towns (Drammen, Harstad and Stavanger, 515,602 person years) during the period 1 January 1988 to 31 December 1990 was studied on the basis of data form The Norwegian Injury Register. 1,104 such fractures occurred during the study period (21 per 10,000). The incidence increased with age from 12 per 10,000 in the age group < or = 14 years, to 47 per 10,000 in the group > or = 65 years. 57% of all patients with fractures were under the age of 65. Higher incidence during the winter months was observed in all three towns during the whole period. The increase occurred in the age groups 25-64 and > or = 65 years, both in males and females, but not in the age groups < or = 14 or 15-24 years. In 1990 we obtained more accurate information on the injury incident. 39% of all the fractures were caused by slipping on ice or snow. 45% of these were fractures of the elbow or lower arm. There seems to be a substantial potential for targeted preventive measures. PMID- 8209323 TI - [Telemedicine--a review]. AB - Modern telecommunication technology enables medical information and images to be transmitted from the general practitioner to a hospital or between hospitals. This allows the specialist to interactively conduct and control the examination carried out by the GP via the two way sound and picture connection within radiology, pathology, dermatology, psychiatry, cardiology and otorhinolaryngology. The diagnostic quality of the technique is equal to that of an ordinary examination. The method gives the patients access to adequate medical expertise in their home environment, is highly effective and saves cost of transport. The patients are satisfied with being able to meet the experts this way. PMID- 8209324 TI - [Gynecologic help in Bosnia. Zenica, Bosnia, Europe--February 1994]. PMID- 8209325 TI - [The Frihamn center--an alternative of district psychiatry]. PMID- 8209326 TI - [Drugs and meals. Together--or separately?]. PMID- 8209327 TI - [An interest group for stroke-related diseases in Norway]. PMID- 8209328 TI - [Where is Norwegian ophthalmology going?]. PMID- 8209329 TI - [Are leadership principles of the private sector valid for hospital leadership?]. PMID- 8209330 TI - [Physicians and journalists]. PMID- 8209331 TI - [Devaluation of educational surgery departments in northern Norway]. PMID- 8209332 TI - [Microbes strike back]. PMID- 8209333 TI - [Preventive psychiatry in accidents and disasters]. PMID- 8209334 TI - [Controls are a nuisance]. PMID- 8209336 TI - [Quality control and use of resources in colonoscopy. A prospective evaluation of 1000 colonoscopies]. AB - In a prospective study 1,000 consecutive colonoscopies were registered in a specially designed database. Mean time spent on colonoscopy was 26.3 minutes. 419 colonoscopies were technically difficult. The desired level in the gut was reached in 747 examinations. There were two non-fatal complications. Both were haemorrhages following snare polypectomies. One third of the colonoscopies were control examinations. If we followed the commonly accepted policy for control of colitis and neoplasms, in a few years time, all our capacity would be used for routine examinations. A consensus for selection of patients for colonoscopy is needed. We found 107 of 230 double-contrast barium enema examinations to be false negative or false positive. This is a higher figure than obtained with colonoscopy. PMID- 8209335 TI - [Findings in 1000 colonoscopies at a county hospital. A prospective study]. AB - 1,000 colonoscopies were registered in a specially designed database. The database software secured complete registrations. We present the diagnostic results according to symptoms and pattern of bleeding. One third of the colonoscopies were routine examinations of malignant or benign neoplasms and ulcerative colitis. We found malignancy to be much more frequent in newly referred patients than in the routine control group. Pathology was found in particular in patients with overt or occult lower gastrointestinal bleeding. Colonoscopy should be a primary diagnostic procedure in the event of lower gastrointestinal tract bleeding. The authors discuss the benefit of routine colonoscopic follow-up of neoplasms and ulcerative colitis. PMID- 8209337 TI - [A shipwreck and organization of the psychosocial support work]. AB - During recent years attention has been drawn to the importance of psychosocial support to victims of accidents and disasters. Post-traumatic stress disorder seems to be more frequent than earlier believed, and early psychosocial assistance is thought to reduce the psychological effects of the traumatic experience. The authors describe the psychosocial work, as it was organized at Haukeland Hospital, after a shipwreck. Experiences with mobile medical teams with stress competence are also discussed. PMID- 8209338 TI - [Symptomatic gallstones in a patient with heart transplantation. A serious and little observed adverse reaction of cyclosporine A]. AB - A 53 year old male patient developed symptomatic cholelithiasis shortly after a heart transplantation following postinfarction heart failure. The patient was both initially cholecystectomized and later endoscopically treated for recurrent biliary pain and multiple concrements in the choledochus. He did not present any of the known predisposing risk factors for developing biliary stones. The possible role of cyclosporine in inducing biliary stones is discussed. PMID- 8209339 TI - [Dissolution of gallstones with methyl-tert-butyl ether. An alternative to surgery in high risk patients]. AB - We treated 27 symptomatic patients by dissolving cholesterol gallstones with methyl tert-butyl ether. Three patients were treated twice. Mean age was 70.2 years. Most patients had elevated risk for surgery. A 5 French polyethylene catheter was introduced percutaneously, transhepatic to the gallbladder. The placement of the catheter was successful in 26 of 30 procedures (87%). Cholecystography showed complete dissolution of stones in 22 of 26 patients treated (85%). Mean treatment time was 11.7 h. In four patients the treatment was stopped before dissolution was complete. Side effects were nausea, pain, fever and vasovagal reaction. 15 patients were followed up for a mean of 22.7 months after dissolution. Ten patients had no biliary symptoms, five patients suffered symptomatic relapse and three had asymptomatic recurrence of stones. We conclude that dissolution of gallstones by methyl tert-butyl ether is an adequate alternative to surgery in selected high risk patients. PMID- 8209340 TI - [Insulin pumps and drop in pressure]. AB - Do insulin pumps deliver more insulin at lower environmental pressures and, if so, is this due to pump dysfunction or to formation of bubbles in the insulin solutions? H-TRON V-100 (Hoechst Infusor V-100), MRS-1 (Disetronic), Nordic Infusor MK II (Novo Nordisk) and Minimed 504-S (Minimed Technology) insulin pumps were studied at 0.9 ATA and 0.8 ATA with constant infusion 2.0 I.U./hour. H-TRON V-100 was also studied at 0.7 ATA at the same infusion rate and with the motor in stop position. The results indicated that all pumps delivered slightly more insulin than the set rate during decompression (max. single value 2.68 I.U. extra delivered at 0.7 ATA, max. average value 1.32 I.U. extra delivered at 0.8 ATA). An equivalent amount of insulin (1.72 I.U.) was delivered at 0.7 ATA without running the motor. This implies that the extra insulin supplied was caused by physically dissolved nitrogen and oxygen in the insulin solution, and was not due to dysfunction of the pumps. PMID- 8209341 TI - [Pseudomonas aeruginosa as a cause of urinary tract infections]. AB - The aim of this study was to investigate risk factors for urinary tract infection with Pseudomonas aeruginosa, the course of such infection and the therapeutic approach among doctors. A total av 56 patients were included. Identified risk factors were old age, institutionalization, obstruction or other dysfunction of the urinary tract, use of urinary tract catheters and treatment with broad spectrum antibiotics. Urinary tract infection with P aeruginosa has a tendency to persist or relapse. The therapeutic approach varied widely. PMID- 8209342 TI - [Treatment of chronic shoulder tendinitis]. AB - The authors review current treatment modalities and present a study comparing supervised exercises and arthroscopic surgery in patients with rotator cuff disease. Exercises supervised by a physiotherapist emphasize relearning of normal patterns of movement and local endurance training to improve tendon and muscle tissue, and are supplemented by ergonomic advice. The clinician should try to elucidate whether the patient is supposed to benefit solely from information and self-treatment. For several of the currently used treatment modalities, such as ultrasound, soft laser, heat and massage, no effect has been documented. Surgery should be reserved for persons who do not benefit from supervised exercises. Careful rehabilitation is necessary for patients who report having a physically demanding job. PMID- 8209343 TI - [Measles. Meeting with a global health problem]. AB - The present study compares children with measles with children with other diagnoses who were admitted to a small local hospital in Angola in the year of 1988. No differences were observed in the distributions of sex, age or lethality. Nor were any differences found between the children who died from measles and the ones who survived. The children who died from measles did so during the first days after admission. The fact that no significant differences were found shows that measles in this population affected an average of the child population. This underlines the severity of measles as a threat to the health of children in developing countries. PMID- 8209344 TI - [Changes in the use of compulsory measures in Norwegian psychiatric institutions]. AB - This paper presents the second screening concerning the use of coercive measures in Norwegian mental health institutions. The use of mechanical restraint, seclusion and forced medication was recorded during the first six months of 1989 and of 1990. We found no change in the use of coercive measures from 1989 to 1990, nor did we find any differences when the results of this screening was compared with those of the first screening carried out in 1986-88. Mechanical restraint was the most commonly used coercive measure, and a total of 9402 hours of such constraint was recorded the first six months of 1990. In many cases, a substantial part of the total amount of mechanical restraint in the different institutions at different times referred to a single patient, which created large variations in the use of coercion. No correlation was found between the use of coercion on one hand and size of ward and staff ratio on the other; factors that otherwise are believed to be of importance for use of coercion. PMID- 8209346 TI - [Standardization, control and approval of surgical implants in Europe]. PMID- 8209345 TI - [Natural or synthetic surfactant in the treatment of neonatal respiratory distress syndrome]. PMID- 8209347 TI - [Geriatrics. Still a minimum-specialty at Norwegian hospitals]. PMID- 8209348 TI - [When the insurance doesn't approve of sick-listing. Sick-listing--insurance office--the physician]. PMID- 8209349 TI - [Medicine medicalizes reality. Do patients believe in the welfare state?]. PMID- 8209350 TI - [Who can follow-up on "invisible handicaps" in a community?]. PMID- 8209351 TI - [ICPC in practice]. PMID- 8209352 TI - [Legal rights of demented patients in somatic nursing homes]. PMID- 8209353 TI - [The EEC agreements and medical practice]. PMID- 8209354 TI - [Coordination of quality assurance]. PMID- 8209355 TI - [Humans and animals in the Middle Ages]. AB - Some aspects of mediaeval human-animal relationships are presented. In addition to the role of the horse in Germanic cult sacrifices and the significance of domestic animals for the agricultural society of the Middle Ages, the attitude of Christianity to animals is also described. The integration of animals as religious symbolic figures in christian iconography and literature, trials against animals, the importance of tournament sports and hunting for the aristocracy are considered as well as the hippiatry of the court equerries, the equestrian medical practices of the blacksmiths, the possibilities of mediaeval veterinary medicine in the treatment of sick cattle and the use of animal products in medicine. Further sections are dedicated to the nutrition of the mediaeval population and related problems of hygiene, to the introduction of meat inspections and to parasitic disease from food. PMID- 8209356 TI - [The clinical case. Uncastrated male cat, stray, 6 years old, feral]. PMID- 8209357 TI - [Stroke in dogs]. PMID- 8209358 TI - [Scrapie from the clinical aspect]. AB - The first cases of scrapie in the Federal Republic of Germany since 1945 occurred in 1990 and 1991. The disease was found in three flocks of Suffolk sheep and it was probably brought to Germany by breeding sheep from France. Scrapie is a transmissible degenerative disease of the central nervous system with a slowly progressing but always fatal course. The scrapie agent is highly resistant against environmental influences as well as against disinfectants. Incubation period and clinical signs of scrapie vary from flock to flock, depending on genetical factors of infected sheep and depending on the involved scrapie strain. In infected flocks normally not more than 1% of the sheep show clinical symptoms. Affected sheep are usually more than two years old (maximum incidence at three years of age). First signs of the disease may be changes in behaviour or pruritus or locomotor symptoms. When the disease progresses, all sheep loose flesh and within some weeks up to some months they get weaker and weaker until they finally die in recumbency. Scrapie cannot be detected in living animals and the disease may be overlooked during autopsy, because in the final stage of the disease many sheep die from non-specific secondary infections. In suspected cases of scrapie, the practicing veterinarian must give a precise history to the pathologist and he must ask for histopathological examination of the brain. PMID- 8209359 TI - [Severe dystocia in cattle caused by peritoneal mesotheliosis of the calf]. AB - A case of congenital peritoneal mesotheliosis in a calf which caused hindrance of parturition necessitating partial fetotomy is described; patho-anatomical, histological and environmental findings are given. PMID- 8209360 TI - [Simulation of an extrauterine pregnancy by a fatty tissue tumor in a Galloway cow]. AB - In an eight-year old Galloway cow, an ectopic pregnancy with mummification of the fetus which had been assumed because of history and clinical examination of the animal was diagnosed as a "tumor of the adipose tissue" (steatitis) following exploratory laparotomy. Possible problems of obesity in cows of extensively kept breeds are discussed. PMID- 8209361 TI - [The hemoglobin concentration in the blood of dairy cattle of different breeds and their offspring during the peripartum period]. AB - Blood samples taken repeatedly from dairy cows on pasture (50 Holstein-Friesian) and then from 181 cows and their newborn calves within 5 to 10 min after birth were used for measurement of haemoglobin content (Hb). Hb decreased with ongoing lactation and pregnancy, increased several weeks before parturition and reached its highest value shortly after birth. There was some individual, breed and age specificity of Hb in dairy cows. Assisted calvings using marked traction resulted in no difference in Hb values of the cows when compared to other calvings; whereas the calves' Hb values were smaller and the difference between calf Hb and cow Hb was greater. A strong correlation between Hb of the cow and Hb of the newborn calf and the difference Hb calf-Hb cow could be found. PMID- 8209362 TI - [Congenital cavernous hemangioma in a brown Swiss calf, a rare oral blastoma. Case report]. AB - A congenital cavernous hemangioma was found in the pars incisiva of a newborn Brown-Swiss calf. The tumour was characterized by locally invasive and destructive growth. Histopathological investigation showed a tumour that could be clearly distinguished from a capillary hemangioma as well as from a malignant hemangioendothelioma. PMID- 8209363 TI - [Function and development of autochthonous intestinal flora in domestic poultry]. AB - A report is given on the development and function of the autochthonous intestinal flora in poultry. The relevance of this flora for infections with Salmonella spp., both following egg transmission and oral intake from the 4th to 6th week of life is discussed. PMID- 8209364 TI - [Natural transmission of microsporidia (Encephalitozoon cuniculi) by way of the chicken egg]. AB - 100 chicken embryos were examined for naturally occurring infections with Encephalitozoon cuniculi (E.c.). Two embryos were found to be dead, the others were killed at an age of 18 days. Samples from the oesophagus, intestine, liver, kidneys, heart and brain were collected and examined by immunohistochemical methods. E.c. was found in about 40% of the embryos. This microsporidian was observed in all organs, particularly, however, in the oesophagus, intestine, brain and heart. The number of E.c. was significantly larger in the two embryos that died than in the others. The investigations demonstrated, that E.c. may be transmitted naturally to the chicken egg. Further, the results suggested that E.c. may be a cause of death in chicken embryos. In most cases, however, E.c. infections are inapparent in embryos. Such inapparent infections may be an important way of contamination of chicken production units with E.c. PMID- 8209365 TI - [Pemphigus foliaceus in a foal. A case history]. AB - The clinical history, clinical, pathological and immunohistological findings of a four-month-old foal with generalised pemphigus foliaceus are presented. The typical lesions of this autoimmune skin disease are described and discussed. PMID- 8209367 TI - [The thyrotropin-releasing hormone (TRH) test in the dog: injection or infusion?]. AB - The injection of 200 micrograms TRH per dog for the examination of thyroid function is superior to the long term infusion of 200 or 400 micrograms. The maximum of T3 can be measured two, and of T4 and FT4 four hours after TRH administration. FT4 reacts as the most sensitive parameter after both injection and infusion. PMID- 8209366 TI - [Case report of a complex odontoma in a horse--clinical picture, radiography, ultrasonography and computed tomography]. AB - The clinical signs, diagnosis and pathology of an adult horse with a complex odontoma are described. Computer tomography was shown to be a new diagnostic technique with outstanding potential in the investigation of diseases of the equine head. PMID- 8209368 TI - [Intestinal lymphangiectasis in the dog. A literature review with a case history]. AB - A literature review of intestinal lymphangiectasia in the dog is presented. A Yorkshire terrier with acquired lymphangiectasia as the result of enteritis is described. The single clinical symptom was marked ascites. Diagnosis was confirmed by histology, demonstrating dilated lymph vessels in the intestinal villi of the duodenum. PMID- 8209369 TI - [Hepatozoon canis: an important parasitic infection in dogs]. AB - This paper reports on a case of hepatozoonosis of a dog imported from Italy to Germany. A survey of the biology and ecology of the causative agent as well as the pathogenesis, clinics, diagnosis, therapy and prophylaxis of Hepatozoon canis infection is presented. PMID- 8209371 TI - [Cystic changes of the skin caused by Dermocystidium koi in koi carp]. AB - Skin infection in koi carp by Dermocystidium koi is described. Symptoms of disease and the parasite are illustrated. PMID- 8209370 TI - [The blood gas status in bitches with pyometra-endometritis complex]. AB - The blood gas status of 52 bitches presented with pyometra-endometritis complex was examined. Nine healthy bitches with a normal sexual cycle served as control group. Depending on the clinical symptoms, the sick bitches were divided into two groups (A and B). Compared to the control group, both test groups showed significant differences in pH, HCO3 and base excess levels. A correlation between the severity of disease and the decreasing pH level was noted. The disturbance of acid-base balance also resulted in respiratory and metabolic acidosis. A high proportion of these acidotic states was not compensated (group A: 71.4%; group B: 50.0%). PMID- 8209372 TI - [Urolithiasis in a green iguana (Iguana iguana)]. AB - In this report surgery on the urinary bladder of an iguana is documented. Clinical signs, palpation and radiography failed to reveal the cause of the illness. During surgery a distended urinary bladder which contained an urolith 3 x 2 cm in size was found and removed. The urinary bladder was closed with a double-layered, non-perforating suture. According to the results of infrared spectroscopy, the urolith consisted of 70% dehydrated uric acid and 30% ammonium hydrogen urate. After removal of the urolith the iguana recovered within two days. PMID- 8209373 TI - Circulatory failure caused by a fungicide containing iminoctadine and a surfactant: a pharmacological analysis in rats. AB - The fungicide Befran (BFR), containing iminoctadine as an active ingredient and polyoxyethylene alkylether (POEAE) as a surfactant, has been known to cause circulatory failure in human acute oral poisoning. We investigated separately the effects of iminoctadine, POEAE, and BFR on heart rate and blood pressure of rats and also on isolated atria and aortas. In isolated rat atria, iminoctadine produced positive chronotropic and inotropic responses. In contrast, POEAE produced negative chronotropic and inotropic responses. BFR produced no effects at low concentrations, but significant negative chronotropic and inotropic responses at high concentrations. In isolated rat aortas, iminoctadine produced remarkable vasodilative responses, but POEAE produced vasoconstrictive responses. BFR produced both vasodilative and vasoconstrictive responses. When intravenously administered to anesthetized rats, iminoctadine produced hypotension and tachycardia in a dose-dependent manner. POEAE produced significant hypotension and slight bradycardia. BFR, at low doses, produced hypotension without elevation of heart rate. At high doses, it produced significant hypotension and tachycardia. From these results, it can be concluded that severe hypotension induced by BFR is due mainly to the vasodilative effect of iminoctadine and partly to the cardio-suppressive effect of POEAE. PMID- 8209374 TI - Toxic potency of 2,3,3',4,4',5-hexachlorobiphenyl relative to and in combination with 2,3,7,8-tetrachlorodibenzo-p-dioxin in a subchronic feeding study in the rat. AB - Interactive effects on toxicity and biochemical parameters were studied between 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156) and 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) in a 13-week feeding study of female Sprague-Dawley rats. The diets were supplemented with PCB 156 (1.2, 6, or 12 mg/kg), with TCDD (5 micrograms/kg), or with combinations of both compounds. Estimated daily intake of 365 micrograms/kg body wt/day (6 mg/kg diet group) of PCB 156 caused a decrease in body weight gain, thymic atrophy, liver enlargement, a loss in hepatic retinoids, induction of CYP2B activity, and a decrease in plasma thyroxine concentrations. At an estimated daily intake of 81 micrograms PCB 156/kg body wt/day CYP1A1 and CYP1A2 activities were induced. Compared to a simultaneous subchronic feeding study with TCDD a toxic equivalency factor (TEF) between 0.00004 and 0.001 was estimated for PCB 156 with respect to the mentioned effects. Antagonistic effects were found between TCDD and PCB 156 for CYP2B activity and hepatic retinol levels. These effects concurred with a PCB 156 dose dependent decrease in hepatic TCDD levels. Hepatic PCB 156 levels were found to be increased at the 1.2-mg PCB 156/kg dose group in coadministration with TCDD. In conclusion, at least part of the antagonistic effects between PCB 156 and TCDD observed have a toxico-kinetic base. Furthermore, the magnitude of the antagonistic effects may be neglected in comparison with the uncertainty in the TEF value. Therefore, the interactive effects found between PCB 156 and TCDD may have no implications for the additivity of the TEF concept. PMID- 8209375 TI - Effects of benzene metabolites on receptor-mediated phagocytosis and cytoskeletal integrity in mouse peritoneal macrophages. AB - Exposure to benzene can induce a number of hematotoxicities and decrease host resistance to microorganisms and tumors. Several studies have shown that metabolism of benzene to reactive intermediates is required for myelotoxicity. Since receptor-mediated phagocytosis by macrophages is an important host defense, we have examined the effects of benzene metabolites on receptor-mediated phagocytosis in cultured murine peritoneal macrophages. 1,4-Benzoquinone (BQ) was the most potent of the metabolites examined. Ten-minute exposures to a 12.5 microM concentration inhibited Fc and complement receptor-mediated phagocytosis by > or = 90%. Macrophage viability was largely unaffected by BQ treatment. Exposure to 50 and 100 microM 1,2,4-benzenetriol (BT) inhibited Fc receptor mediated phagocytosis by 70 and 95%, respectively. Hydroquinone (HQ) elicited a major decrease (50%) only at 100 microM. The comparative inhibitory potencies of BT and HQ correlate with previously published data on their relative facility for autooxidation to quinones at physiological pH. Catechol had no effect at the concentrations employed. Macrophages treated with BQ and BT failed to recover their Fc receptor-mediated phagocytic capacity when incubated overnight in the absence of the xenobiotics. Only small differences in the inhibition of Fc receptor-mediated phagocytosis were observed between macrophages exposed to BQ at 4 versus 37 degrees C. BQ also had little effect on the Fc receptor binding of target cells. Fluorescent digital imaging microscopy demonstrated that BQ treatment markedly decreased the filamentous actin content of macrophages. However, BQ bound in low amounts to purified actin and did not affect its assembly. Our findings suggest that a mechanism for inhibition of Fc receptor mediated phagocytosis by BQ is disruption of filamentous actin via an effect(s) other than the direct alkylation of actin by BQ. PMID- 8209376 TI - Peroxisomal proliferators inhibit acyl CoA synthetase and stimulate protein kinase C in vivo. AB - The mechanism by which hypolipidemic drugs and industrial plasticizers cause hepatic tumors in rodents remains unknown. It is known, however, that protein kinase C is elevated during hepatic cell turnover, and sustained cellular replication is correlated with an increased incidence of hepatic tumors. Therefore, several peroxisomal proliferators varying in their tumorigenic potency in chronic feeding studies were examined for their ability to increase protein kinase C activity. Intragastric administration of (4-chloro-6-(2,3-xylidino)-2 pyrimidinylthio)acetic acid (Wy-14,643; 100 mg/kg) increased protein kinase C activity threefold in 5 hr and fivefold in 10 hr. Perfluorooctanoate also increased protein kinase C activity significantly in microsomes at 5 hr. Wy 14,643 and perfluorooctanoate also diminished acyl CoA synthetase activity significantly, with Wy-14,643 exhibiting competitive type kinetics. Other peroxisomal proliferators were examined [e.g., ciprofibrate, clofibrate, 2 ethylhexanol, valproate, and di(ethylhexyl)phthalate (DEHP)] and collectively an inverse relationship between their ability to stimulate protein kinase C activity and inhibit acyl CoA synthetase was observed (r = -0.80). All chemicals examined had no direct effect on protein kinase C activity in vitro. Interestingly, those compounds which are more potent as hepatocarcinogens (e.g., Wy-14,643) in long term feeding studies decreased acyl CoA synthetase and elevated protein kinase C activity to a greater extent than their weaker counterparts (e.g., DEHP). It is proposed that inhibition of acyl CoA synthetase by peroxisomal proliferators elevates free fatty acids which stimulate protein kinase C activity and ultimately promote tumor formation. PMID- 8209377 TI - The nephrotoxicity of intravenously administered cadmium-metallothionein: effect of dose, mode of administration, and preexisting renal cadmium burden. AB - Exogenously administered cadmium-metallothionein (Cd-MT) is highly nephrotoxic, producing renal damage similar to that seen following chronic Cd exposure. However, nephrotoxicity following Cd-MT administration occurs at a much lower renal Cd concentration than that following chronic Cd exposure. In the present study, the sensitivity of female rats to bolus and infused doses of Cd-MT was evaluated. The Cd-MT was administered via the jugular vein either as a bolus or infused over a 24-hr period via osmotic minipumps in naive rats and in rats which had been pretreated with 5 microM CdCl2/kg, sc, five times/week, for 9 weeks. Renal toxicity was evaluated by urinary lactate dehydrogenase, protein, and MT excretion. In naive rats, a bolus dose of 0.15 mg Cd/kg as Cd-MT was nephrotoxic. In comparison, a two-fold higher infused dose was required to cause nephrotoxicity. In Cd-pretreated rats, a bolus dose of 0.45 mg Cd/kg as Cd-MT was necessary to produce nephrotoxicity, presumably because Cd pretreatment yielded renal MT levels that were about 15 times higher than the levels in naive animals. Although a bolus dose of 3 mg Cd/kg as CdCl2 resulted in a renal Cd concentration about 1.5 times that found after administration of 0.15 mg Cd/kg as Cd-MT, it did not produce any nephro-toxicity. The results of this study suggest that a renal Cd concentration, which is nephrotoxic if the Cd-MT is administered as a bolus dose, is well tolerated if the Cd-MT is delivered at a sustained level over a 24 hr period. Furthermore, the preexisting renal Cd burden reduces the sensitivity to nephrotoxicity of Cd-MT, presumably due to elevated MT levels available for sequestration of incoming Cd. We conclude that mere accumulation of Cd in the kidney does not necessarily result in nephrotoxicity; instead, the circulating Cd MT level, as well as the intracellular MT concentration, appear to be the more important determinants of nephrotoxicity. PMID- 8209378 TI - Evaluation of the dysmorphogenic effects of procarbazine, benzylazoxyprocarbazine, and methylazoxyprocarbazine in whole embryo culture. AB - Serum from procarbazine (PCZ)-treated rats is dysmorphogenic to rat embryos cultured in vitro, but PCZ is not effective when added directly to culture medium, even with an exogenous metabolizing system. Methylazoxyprocarbazine (MPCZ) is a metabolite which we have identified by HPLC in the dysmorphogenic serum of PCZ-treated rats. PCZ, MPCZ, and benzylazoxyprocarbazine (BPCZ, an isomer of MPCZ) were tested in rat whole embryo culture to determine their effects on embryo development. The parent compound, PCZ, produced no effect on embryo growth or development at concentrations up to 200 micrograms/ml. MPCZ proved to be the most potent of the agents tested. There was significant embryo lethality at concentrations of > or = 10 micrograms/ml while 25 micrograms/ml had significantly reduced embryonic developmental score (DEVS), and 35 micrograms/ml reduced DEVS, head length, and somite number. There was 89% embryo lethality at the 50 micrograms/ml exposure level. At concentrations > 5 micrograms/ml, there were significant increases in anomalies, primarily, failure of neural tube closure, erratic neural seam, and microcephaly. In contrast, BPCZ produced embryo lethality and reductions in DEVS only at 100 micrograms/ml. These data suggest that MPCZ, which has been identified in PCZ-treated rat serum, may be the proximate dysmorphogenic metabolite of PCZ. PMID- 8209379 TI - Acetaminophen nephrotoxicity in CD-1 mice. I. Evidence of a role for in situ activation in selective covalent binding and toxicity. AB - Acetaminophen (APAP) administration (600 mg/kg, ip) to 18-hr-fasted, 3-month-old male CD-1 mice results in necrosis of the renal convoluted proximal tubules. To selectively inhibit APAP activation in the kidney but not in the liver, 10-week old male CD-1 mice were castrated under ether anesthesia and allowed to recover for a minimum of 2 weeks before use. Microsomal activation of APAP in vitro was monitored by trapping the APAP-derived electrophile as an N-acetylcysteine conjugate. Production of the conjugate was significantly decreased in renal microsomes from castrated mice. By contrast, hepatic microsomal production of the APAP conjugate was not changed by castration. Castration also did not alter APAP covalent binding in liver or APAP hepatotoxicity. Also, the overall metabolism of APAP was not altered by castration, as there were no significant differences in the 24-hr excretion of APAP urinary metabolites between castrated and sham operated mice. However, castration did significantly protect mice against APAP nephrotoxicity, as evidenced by decreases in plasma urea nitrogen levels and in the severity of histopathologic damage assessed 12 hr after APAP. Castration also reduced the level of selective covalent binding of APAP metabolites to renal proteins as detected on Western blots with affinity-purified anti-APAP antibodies. These findings suggest that, for the mouse, intrarenal biotransformation of APAP to a reactive electrophile significantly contributes to the APAP covalent binding within the kidneys and the subsequent nephrotoxicity. PMID- 8209380 TI - Environmental hormone disruptors: evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites. AB - Recent studies with vinclozolin, a dicarboximide fungicide, demonstrate that perinatal exposure to 100 mg vinclozolin/kg/day from Gestational Day 14 through Postnatal Day 3 inhibits morphological sex differentiation. At 1 year, treated male rats exhibited hypospadias, cleft phallus, suprainguinal ectopic testes, a vaginal pouch, epididymal and testicular granulomas, and atrophic seminal vesicles and ventral prostate glands. This pattern of malformations suggests that this fungicide possesses antiandrogenic activity. To test this hypothesis, we examined the ability of vinclozolin to inhibit the conversion of testosterone to the more potent androgen 5 alpha-dihydrotestosterone via 5 alpha-reductase (EC 1.3.1.22) and to compete with androgen for binding to the androgen receptor. The results indicate that neither vinclozolin nor its degradation products, 2-[[(3,5 dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1) and 3',5'-dichloro-2 hydroxy-2-methylbut-3-enanilide (M2), inhibit 5 alpha-reductase activity. Although the ability of vinclozolin to compete with androgen for binding to the androgen receptor was weak (Ki > 700 microM), the two vinclozolin metabolites, M1 and M2, were effective antagonists of androgen receptor binding (Ki = 92 and 9.7 microM, respectively). As the concentrations of M1 in the serum of pregnant rats and their pups on Postnatal Day 3 meet or exceed the in vitro Ki for androgen receptor inhibition, we suggest that the demasculinizing effects of vinclozolin exposure in vivo also may be mediated via the antiandrogenic metabolites M1 and/or M2. PMID- 8209381 TI - Reduced ability of rat preantral ovarian follicles to metabolize 4-vinyl-1 cyclohexene diepoxide in vitro. AB - 4-Vinylcyclohexene diepoxide (1-epoxyethyl-3,4-epoxycyclohexane, VCD), an industrial chemical, is a potential health hazard because it destroys oocytes in small preantral follicles in rats. We proposed that VCD destroys oocytes in these follicles because of their reduced capacity to detoxify VCD (convert VCD to tetrol, 4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane). Ovaries, livers, and adrenal glands were collected from immature and mature Fischer 344 rats. Tissues were dissociated and ovarian tissue was separated into distinct follicular fractions. Tissues were incubated with [14C]VCD and media were assayed for [14C]tetrol by HPLC. In immature rats, conversion of VCD to tetrol in large preantral follicles and hepatocytes was 1.5-fold greater than in small preantral follicles and 4-fold greater than in ovarian interstitial cells (p < 0.05). In adults, conversion of VCD to tetrol in large preantral follicles and hepatocytes was, respectively, 3- and 10-fold greater than in small preantral follicles and interstitial cells (p < 0.05). Compared with immature rats, all tissues from adult rats converted more VCD to tetrol (p < 0.05). These data demonstrate that interstitial cells and small preantral follicles from adult and immature rats have a reduced capacity to convert VCD to tetrol compared to large preantral follicles and liver cells. This may explain their increased susceptibility to VCD induced ovotoxicity. Furthermore, adult rats may be less susceptible to VCD induced ovotoxicity than immature rats. PMID- 8209382 TI - Hydrazine genotoxicity in the neonatal rat. AB - The neonatal rat, because of its relatively rapid rate of liver DNA replication without chemical or surgical induction, was used to assess the genotoxicity of the carcinogen hydrazine. Hydrazine is a more potent acute toxicant in the neonate than in the adult rat. Administration of hydrazine sc (1.5-50 mg/kg body wt) to newborn rats during the period of rapid liver DNA synthesis, 72-96 hr after birth, resulted in the formation of 7-methylguanine and O6-methylguanine in hepatic DNA; O6-methylguanine was seen only in animals given near-lethal doses of the carcinogen. Methylguanines were detectable in liver DNA only when the dose of hydrazine was necrogenic, but lethal doses of hydrazine to neonates produced more methylguanines in liver DNA than in adult rats given equal doses. Southern analyses were performed on liver DNA from neonates treated with 25 or 50 mg hydrazine/kg, doses which were necrogenic to the liver. The results indicated that one or more MspI restriction sites (5'-C decreases CGG-3') were lost or blocked in liver DNA from hydrazine-treated animals and that these sites were located at or near the genes for gamma-glutamyl transpeptidase and cytochrome P450 IIB1. Restriction sites near albumin, H-ras, and cytochrome P450 IIE1 genes cut by MspI, HpaII, or HhaI did not appear to be affected by hydrazine treatment. The results suggest that hydrazine-induced damage is not random in the DNA molecule. The neonate shows less DNA adduct formation at low doses of hydrazine, but higher levels at high doses. PMID- 8209383 TI - Lactate dehydrogenase activity and isozyme patterns in tissues and bronchoalveolar lavage fluid from rats treated with monocrotaline pyrrole. AB - Monocrotaline pyrrole (MCTP), a putative, toxic metabolite of monocrotaline, induces delayed and progressive lung injury, vascular remodeling, and pulmonary hypertension in rats. The lung injury is characterized by increased wet lung-to body weight ratio followed by increases in lactate dehydrogenase (LDH) activity and protein concentration in the cell-free bronchoalveolar lavage fluid (BALF) and increased cellularity of BALF. We evaluated total LDH activity and isozyme patterns in the tissues, cell lysates, sera and cell-free BALF of rats after treatment with MCTP to determine the source of increased LDH activity. Male Sprague-Dawley rats were given a single injection of MCTP (3.5 mg/kg) or an equal volume of the N,N-dimethylformamide (DMF) vehicle in the tail vein on Day 0. Rats were killed at 4, 8, or 14 days after toxicant administration, and several markers of lung injury, LDH activity, and isozyme patterns of various tissues, cells, and body fluids were determined. At 8 and 14 days, the lungs from MCTP treated rats had multifocal, irregularly shaped lesions of hemorrhage and consolidation. At Day 14 only, the hearts of MCTP-treated rats appeared enlarged and there was right cardioventricular hypertrophy. Rats treated with MCTP had no macroscopic lesions in kidneys, liver, or skeletal muscle. Compared to controls, MCTP-treated animals had no change in total LDH activity or isozyme patterns of samples of lungs, heart, skeletal muscle, liver, kidneys, or erythrocyte lysates. Changes in LDH activity in the cell-free BALF and BALF cell pellet from rats treated with MCTP were characterized by increases in isozymes LDH4 and LDH5 and an elevated LDH4/LDH5 ratio in the BALF only. Our results suggest the most probable source of the increased LDH activity in cell-free BALF of MCTP-treated rats originates from the lung tissue and is consistent with a contribution from the pulmonary vascular endothelium, a source rich in LDH4. A combination of plasma, macrophages, and neutrophils in the pulmonary tissue may also have made minor contributions to the increase in cell-free BALF LDH activity, particularly to the activity of LDH5. PMID- 8209384 TI - Acute behavioral toxicity of pyridostigmine or soman in primates. AB - Effects of a peripherally active carbamate (pyridostigmine bromide) and a centrally active organophosphate (OP) nerve agent (soman) on performance by rhesus monkeys of a compensatory tracking (primate equilibrium platform, or PEP) task were measured using a balanced Latin-square design to determine the ED50 for pyridostigmine (0.66 mg/kg) and the up-and-down (titration) method to determine the ED50 for soman (2.50 micrograms/kg). We concluded that the PEP performance model is a sensitive and reliable indicator of anticholinesterase (anti-ChE) behavioral toxicity. We also found that soman, an irreversible inhibitor of acetylcholinesterase (AChE), is more than 100 times more behaviorally disruptive than the reversible peripheral inhibitor pyridostigmine, as indicated by the difference in ED50 doses expressed in molar terms. Soman's behavioral toxicity is severe at levels of serum cholinesterase inhibition (70-80%) at which pyridostigmine does not significantly affect performance. As a prophylactic treatment for OP agent poisoning, pyridostigmine has a substantial safety factor, since behavioral toxicity becomes significant only at approximately four times the proposed therapeutic dose. PMID- 8209386 TI - The effects of chlordane exposure during pre- and postnatal periods at environmentally relevant levels on sex steroid-mediated behaviors and functions in the rat. AB - Technical chlordane is a mixture of four main isomers (i.e., heptachlor, cis chlordane, trans-chlordane, and trans-non-achlor) found in meat and dairy products as well as in indoor air of houses treated for termites. These isomers are metabolized to more potent epoxides (heptachlor epoxide and oxychlordane) which accumulate in lipid compartments of tissues and have been shown to reduce chloride influx through GABAA receptor complex channels and to alter steroid levels. However, considering the almost universal human exposure and the potential for accumulation of these agents, very little is known about how chronic, low-level exposures during development affect adult behavior and steroid mediated processes. Time-pregnant Sprague-Dawley dams (Day 4 of gestation through Day 21 of lactation) and offspring (Day 22 of age through Day 80) were exposed to three levels of technical chlordane (100, 500, or 5000 ng/g) on a daily schedule. The low-exposure level generated heptachlor epoxide and oxychlordane plasma levels in the dam (Day 20) and in the offspring (Day 80) representative of those found in the U.S. populace. Chlordane-dosed offspring exhibited sex- and dose dependent effects on testosterone levels, behavioral tests, and body weight conducted between postnatal Days 77 and 85. Chlordane-dosed females, but not males, had significant decreases in testosterone levels, significant improvements in spatial abilities (i.e., decreases in Cincinnati maze errors, navigation times, and failures to escape), and significant increases in body weight and in auditory startle-evoked responses. In two other tests, only males were used. These chlordane-dosed males showed significant increases in male-typical mating behaviors and decreases in 36Cl- uptake into brain microsacs. For all behavioral and body weight measurements, dose-response effects were observed for the 100 and 500 ng/g dosed groups. However, the 5000 ng/g dose group responses were closer to those of control values. These results suggest that these cyclodienes masculinize sexually dimorphic functions and behaviors by mimicking sex steroids and/or changing their levels. PMID- 8209385 TI - Protein oxidation and amino acid-DNA crosslinking by nickel compounds in intact cultured cells. AB - Oxidative damage induced by NiCl2 to protein has been investigated. We found that nickel induced a dose-dependent increase in the oxidation of bovine serum albumin (BSA) as detected by carbonyl formation in the presence of H2O2 in vitro, as well as producing carbonyl of proteins in intact cultured Chinese hamster ovary (CHO) cells. Other metals capable of producing oxidative damage to BSA in the presence of H2O2 included Cu, Co, Fe, and chromate. However, Cd2+, Hg2+, and Pb2+ were not active even in the presence of H2O2. As an indicator of nickel-induced genotoxic damage, the crosslinking of amino acids to DNA was also examined. Cysteine, histidine, and tyrosine were increased in their association with DNA based upon their persistent binding to DNA following washes with EDTA or SDS. The results suggest that DNA-protein or DNA-amino acids crosslinks induced by nickel may result from interaction of the nickel-oxidized carbonyl group of protein, peptides, and free amino acids. PMID- 8209387 TI - Protection of cytochrome c oxidase against cyanide inhibition by pyruvate and alpha-ketoglutarate: effect of aeration in vitro. AB - Toxicity of cyanide is related to its inhibitory action on cytochrome c oxidase (COx). The alpha-keto acids pyruvate and alpha-ketoglutarate are known to exert in vivo certain protective effect against CN- toxicity if present when the poison is administered. We characterized in vitro their protection of oxidative phosphorylation and of the activity of COx in rat testis, heart, and liver mitochondria, as well as that of the beef heart enzyme in the pure state. In all cases the keto acids proved to have a protective action, even when KCN was previously added to the incubation mixtures and inhibition had already been established. However, the extent of the protection seemed to depend upon the degree of aeration. In the presence of the alpha-keto acids, O2 succeeded with 77% efficiency in reversing CN- inhibition of [gamma-32P]ATP synthesis under high aeration, whereas only 15% was achieved if aeration was poor. In poisoned heart mitochondria (1 mM KCN) simultaneous estimations of ATP synthesis and COx activity in a closed oxygraph chamber showed a recovery of only 6% of both activities upon the addition of 12 mM pyruvate. Our results suggest that O2 displaced cyanide from the enzyme and the poison was then trapped by the keto acids to form the respective nontoxic cyanohydrin. The combination of both high oxygen concentration and the presence of either pyruvate or alpha-ketoglutarate was necessary to effectively protect COx against cyanide poisoning. PMID- 8209389 TI - Relationships between biomarkers of exposure and neurological effects in a group of workers exposed to acrylamide. AB - A study was performed among 41 workers heavily exposed to a mixture of acrylamide and acrylonitrile in the city of Xinxiang, Henan province, People's Republic of China. The workers underwent a complete medical and neurological examination and provided blood and urine for the determination of several biomarkers of exposure. Among the exposed workers, signs and symptoms indicating peripheral neuropathy were found with statistically significant increased frequencies compared to a group of controls from the same city. Based on neuropathic signs and symptoms and quantifiable indicators of peripheral nervous dysfunction, such as vibration thresholds and electroneuromyography measurements, a neurotoxicity index (NIn) specific for acrylamide-induced peripheral neuropathy was designed. The NIn, which adequately predicted the clinical diagnosis of peripheral neuropathy, was significantly correlated with the levels of mercapturic acids in 24-hr urine, hemoglobin adducts of acrylamide, accumulated in vivo doses of acrylamide, employment time, and vibration sensitivity. The NIn was correlated also with hemoglobin adducts of acrylonitrile, which was explained primarily by a correlation between acrylamide and acrylonitrile exposure in this workshop. However, it was not significantly correlated with momentary measures of exposure such as concentrations of acrylamide in the air or in the plasma of exposed workers. This study is the first in which adduct monitoring has been applied to the same group of individuals in which adverse health effects have been observed. The results seem to indicate that hemoglobin adducts are useful as predictors of acrylamide-induced peripheral neuropathy and that measurements of vibration thresholds are useful for identifying early neurotoxic effects in workplaces with hazardous exposures to acrylamide. PMID- 8209388 TI - Phospholipid metabolism in neural microvascular endothelial cells after exposure to lead in vitro. AB - Lead (Pb2+) is known to alter the permeability of brain capillaries. A possible mechanism for this alteration may be related to the ability of Pb2+ to substitute for Ca2+. Products derived from phospholipid metabolism, namely eicosanoids and diacylglycerol, control endothelial permeability, are partly regulated by intracellular Ca2+, and thus may be sensitive to Pb2+. We asked in this study whether Pb2+ increased arachidonic acid release or stimulated phosphatidylcholine breakdown in an in vitro model of brain capillaries, namely cultured bovine retinal endothelial (BRE) cells. Pb2+ stimulated arachidonic acid release and phosphatidylcholine and phosphatidylinositol metabolism in the presence of ionomycin, but not by itself. More arachidonic acid was released than phosphorylcholine in BRE cells stimulated with ionomycin and Pb2+, but the magnitudes of these responses were similar in cells exposed to ionomycin plus Ca2+. Ionomycin plus Pb2+ or plus Ca2+ resulted in the activation of phospholipase A2, since an increase in lysophosphatidylcholine and arachidonic acid was observed. Protein kinase C was not required for arachidonic acid release because release was observed in cells with a down-regulated enzyme. Ionomycin plus other metals (La3+, Cd2+, or Mg2+) did not result in arachidonic acid release, but Cd2+ or Co2+ inhibited arachidonic acid release by more than 80% when cells were exposed to ionomycin with either Pb2+ or Ca2+. Thapsigargin or maitotoxin plus Ca2+ increased arachidonic acid release that was inhibited by the receptor-dependent calcium channel antagonist SK&F 96365 but not by the voltage dependent calcium channel antagonist nifedipine. However, thapsigargin or maitotoxin plus Pb2+ failed to stimulate arachidonic release. Since in this in vitro model Pb2+ stimulated phospholipid metabolism solely in the presence of an ionophore, the increase in permeability observed in Pb(2+)-exposed animals is probably not due to a release of metabolites of arachidonic acid. PMID- 8209390 TI - Oxygen tension, insulin, and glucagon affect the preservation and induction of cytochrome P450 isoforms in cultured rat hepatocytes. AB - The role of oxygen tension, insulin, and glucagon on the preservation and induction of cytochrome P450 isoenzyme activities and contents was investigated in rat hepatocytes cultured for 4 days on crude liver membrane fractions at 4 or 13% O2. At 13% O2, three out of six immunochemically analyzed P450 isoenzymes were significantly higher than in 4% O2. Exposure to phenobarbital (PB) from Days 1 to 4 dose dependently increased the protein content and decreased the albumin secretion in 13% O2 cultures only. The maximal induction of P450 isoenzymes CYP2B1/2B2 (20- to 25-fold) and CYP2C6 (6-fold) were found at 0.75 mM PB at both oxygen tensions. In contrast, the highest induction of CYP1A1/1A2 (3-fold), of CYP3A (2-fold), and EROD activity were found with 3 mM PB in 4% O2 cultures. CYP2B-dependent testosterone hydroxylation at positions 16 alpha/beta was elevated to a greater extent in 13% O2 cultures (96-fold at 0.75 mM PB) compared to 4% O2 cultures (42-fold). This activity was affected by the insulin concentrations and the insulin:glucagon ratio. With decreasing insulin concentration (100 to 1 nM) or with increasing insulin:glucagon ratios (1:100 1:0.1), the enzyme activity increased preferentially in 4% O2 cultures. The results of these investigations demonstrate that different tissue oxygen tension modulates the responsiveness of the cultured hepatocytes to the glucoregulatory hormones insulin and glucagon and this modulation results in a altered activity of cytochrome P450 isoforms. PMID- 8209391 TI - The study of client-provider interactions: a review of methodological issues. AB - In recent years, increased focus on the quality of family planning and other reproductive health services has led to a better understanding of women's reproductive health needs and has drawn attention to program-client interactions as a critical and neglected dimension of program effort. In this article, the relevant methods and experience related to studying client-provider interactions within family planning programs in southern countries are reviewed. The policy relevance of this work is highlighted first by stressing the operational usefulness of examining what happens when people engage with service-delivery systems that offer family planning or reproductive health services. Subsequently, the content areas encompassed by program-client interactions are clarified by identifying manifest and latent dimensions and by distinguishing the variables that define these interactions from variables related to their determinants and consequences. Finally, a critical review of existing methods is presented, with examples of research and a discussion of ethical issues. PMID- 8209392 TI - Using situation analysis data to assess the functioning of family planning clinics in Nigeria, Tanzania, and Zimbabwe. AB - Situation analyses conducted in Nigeria. Tanzania, and Zimbabwe have revealed problems in the functioning of many of the subsystems of family planning service delivery, namely in supplies of commodities; in facilities and equipment; in staffing and training; in information, education, and communication; and in record keeping. Although a clear pattern of clinic use exists, in that only a few service-delivery points provide contraceptive services to the majority of new family planning acceptors in the three countries, an attempt to explain how clinics with more clients differ from those that are visited less frequently revealed only a weak association between subsystem functioning and use. PMID- 8209393 TI - Use of traditional medical practitioners to delivery family planning services in Uttar Pradesh. AB - This pilot study conducted in Muzaffarnagar district in the state of Uttar Pradesh, India, demonstrates the potential for using traditional medical practitioners in the delivery of family planning services after a brief training period. Practitioners participated continuously in the program for an intervention period of two years during which their services were accepted by the community. The impact of their involvement was reflected in increased knowledge of permanent as well as reversible contraceptive methods and in higher contraceptive use rates, especially of reversible methods adopted by women younger than 25 years (from 8 percent to 37 percent), in the intervention villages, as compared with increased knowledge and use (from 13 percent to 25 percent) of permanent methods alone in the control villages. PMID- 8209395 TI - The impact of condom prices on sales in social marketing programs. AB - The issue of pricing contraceptives in family planning programs is becoming more and more important. What is the relationship between consumer prices and demand, and how can we strike the correct balance between the two? This report examines the correlation between consumer prices for condoms, expressed as a percentage of per-capita gross national product, and per-capita sales of condoms in 24 social marketing programs. The correlation that emerges is strong and negative: Even when the data are controlled for age of program and other independent variables, there is a clear negative correlation between prices and contraceptive sales in these programs. The conclusion is clear that condom prices must be set very low- well below the equivalent of 1 percent of per-capita gross national product for a year's supply--in order to achieve satisfactory prevalence for condoms in either a family-planning or an AIDS-prevention context. PMID- 8209394 TI - Reproductive choice in Islam: gender and state in Iran and Tunisia. AB - This report examines the extent to which reproductive choice is compatible with Islamic principles. It presents the argument that the impact of Islam on reproductive choice is largely a function of the political context in which gender issues are defined. Indicators of reproductive health in countries of the Middle East are reviewed and the way these relate to constraints on reproductive choice is assessed. The examples of Tunisia and Iran are used to illustrate the way in which Islam is invoked to legitimate conflicting positions concerning women and their reproductive options. PMID- 8209396 TI - Morocco 1992: results from the demographic and health survey. PMID- 8209397 TI - The role of peptide in the positive selection of CD8+ T cells in the thymus. AB - Recent experiments using fetal thymus organ culture (FTOC) systems derived from class I deficient mice have provided evidence supporting the view that specific recognition of class I MHC plus peptide complexes is required for the positive selection of CD8+ T cells. The addition of class I binding peptides to FTOC systems derived from beta 2-microglobulin and TAP 1 deficient mice induced the positive selection of CD8+ T cells in a peptide specific manner. The specific recognition of peptide during positive selection implies that the repertoire of specificity's exhibited by CD8+ T cells is at least in part determined by the repertoire of self-peptides presented by class I MHC in the thymus. PMID- 8209398 TI - HMG box proteins in early T-cell differentiation. AB - The central theme of this review is the molecular basis for commitment of cells to the T-cell lineage. Principles of transcriptional regulation are illustrated by two examples; the role of GATA-1 during erythroid differentiation and the function of MyoD-like proteins in myogenesis. Several regulatory proteins have been described in the T-cell lineage. Here, we focus attention on the HMG box family of DNA binding proteins. This recently defined family can be divided in two subfamilies: the HMG/UBF and the TCF/SOX group. The first group contains at least two HMG boxes and binds DNA non-specifically, while the other group of proteins has one HMG box and interacts with DNA sequence-specifically. Characteristics of the most prominent members of both subfamilies will be discussed. In particular, we will address the role of HMG box proteins in controlling the expression of T-cell specific proteins during differentiation. PMID- 8209399 TI - Signal transduction defect in the acquired immunodeficiency syndrome and AIDS related complex. AB - Peripheral blood mononuclear cells from patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), and heterosexual controls were stimulated with anti-CD3 monoclonal antibody, phorbol myristate acetate (PMA), or both and 3H thymidine incorporation and IL-2 receptor (IL-2R alpha; CD25; Tac antigen) expression were measured. In addition, basal plasma membrane potential and plasma membrane potential following anti-CD3 stimulation were compared between the three groups. A significantly reduced DNA synthesis and CD25 expression was observed in both AIDS and ARC upon stimulation with anti-CD3 or PMA. Although, a significant synergism was observed with anti-CD3 plus PMA stimulation in both AIDS and ARC, and the responses were normalized to the levels of anti-CD3 or PMA response in normal control, the levels were significantly lower than those observed with anti-CD3 plus PMA in controls. Plasma membrane potentials were decreased (membrane depolarized) in both ARC and AIDS (AIDS > ARC), and anti-CD3 had no effect on further depolarization of plasma membrane in AIDS. These data suggest a defect in signal transduction pathway in patients with HIV-1 infection. PMID- 8209400 TI - Athymic (nude) mice fail to delete functional self-reactive helper T cells. AB - We have examined the thymic requirement for the antibody response to a foreign antigen coupled to self erythrocytes. We find that self erythrocytes mediate thymus-independent, carrier specific help for the antibody response to the pneumococcal cell wall polysaccharide antigen, PnC. Thus, athymic nude mice gave a high primary antibody plaque-forming cell (PFC) response to PnC-mouse RBC but a low response to PnC coupled to sheep or burro RBC. The meager response to PnC coupled to foreign RBCs could not be attributed to antigenic competition since the response to the carrier (burro RBC) was < 100 PFC per spleen. Reconstitution of nude mice with splenic T cells from euthymic mice enhanced rather than suppressed the antibody response to PnC-mouse RBC. The results document that in the absence of thymic deletion, functional self-reactive helper cells persist in the nude mouse. PMID- 8209401 TI - Thymus histogenesis in the lizard, Chalcides ocellatus. AB - Different stages of thymus morphogenesis and thymocyte differentiation have been studied at the ultrastructural level in the lizard, Chalcides ocellatus. On stage 36 of embryonic development, the thymus primordium was composed principally of undifferentiated epithelial cells and some lymphoid stem-cells. From stage 37 to 38, the lymphoid stem-cells differentiate into lymphoblasts and then transform into typical lymphocytes. A clasmotosis phenomenon seems to be involved in this transformation. In the developing cortical regions, lymphoblasts accumulated rapidly, stretching the epithelial cells which become stellate in shape. From stage 39 to 40, a phase of intense proliferation occurs and numerous lymphocytes die in the thymic tissue and are phagocytosed by macrophages. On stage 41, the presence of interdigitating cells in the medullary area completed cortico medullary differentiation. On neonatal and juvenile lizards, small cortical thymocytes differentiated and the thymus possessed all characteristic of an adult thymus. Thus, at birth, the histogenesis of the lizard thymus was achieved and the only further modification consisted in a gain of weight. PMID- 8209402 TI - [A restrictive antibiotic policy prevents hospital infections]. PMID- 8209403 TI - [Danish research of health care function and results should be increased]. PMID- 8209404 TI - [Staphylococcus aureus--33-year epidemiology in Denmark. From hospital epidemics to endogenous infections?]. AB - Data on 591,292 Staphylococcus aureus strains from Danish patients in the period 1960-1992 have shown that penicillin- and streptomycin-resistant strains of the 52,52A,80,81 phagetype complex dominated around 1960 and were replaced by multiresistant strains of the 83A complex during 1965-1975. Since then the majority of the strains have been resistant to penicillin only, firstly due to an increased occurrence of the 94,96 complex followed by strains of type 95 and group II. Today only 0.2-0.3% of the strains are multiresistant and often originate from patients hospitalized abroad. In the first half of the observation period strains from hospitals were more antibiotic-resistant and dominated by special phagetypes compared to community-strains, today there are no differences. Hospital outbreaks with S. aureus have in recent years only rarely been detected in Denmark and phagetyping results might indicate that today patients are mainly infected by their own strain. In the future, infection control and surveillance of antibiotic resistance and phagetypes should be continued together with new studies on carriage and foreign body infections. PMID- 8209405 TI - [Long-term carrier state of methicillin resistant Staphylococcus aureus after hospitalization]. AB - In Denmark, strains of methicillin-resistant (MR) Staphylococcus aureus constitute less than 0.1% of all S. aureus isolates and are often acquired abroad. A strain of MR S. aureus phage type 77+ was isolated from a patient, who had been hospitalized in a Portuguese hospital three months earlier. In Denmark, the patient had been admitted to a private clinic for replacement of the aortic valve and a coronary bypass operation. The strain did not produce detectable soluble coagulase, and it was multiply resistant, including resistance to gentamicin, tetracycline, erythromycin, and rifampicin. It was probably non invasive. Thirty-seven members of the staff were screened for MR S. aureus with negative results. The patient was treated with chlorhexidine to eliminate carriage, but, eight weeks after treatment, he was still colonized. Thus, in the current epidemiological situation in Denmark, it is important to take into consideration that carriage of MR S. aureus may last several months. We therefore suggest, that specific guidelines for hospital hygiene should be upheld not only for patients, who are transferred directly from hospitals in other countries, but also for patients, who have been hospitalized abroad within the last three to six months. PMID- 8209406 TI - [Support to spouses of patients with cancer]. AB - Psychosocial problems frequently arise in the families of cancer patients. Using a questionnaire, information about the problems experienced by 120 spouses to cancer patients was collected. The response rate was 85%. The results show that the patient and the children are the most important persons in supporting the spouses. Sixty-one percent felt relieved of having somebody to talk to about their problems. The amount of contact to friends and family mainly remained unchanged. Approximately 1/3 of the spouses had to work more than the normal 37 hours a week, which compromised their abilities to support the patients. Professional help was sought by 1/4 of the spouses in an attempt to solve their problems in relation to the patient's disease. Men are more likely to have their problems solved by professional support than women. Among the spouses there is a great wish for information and support offered primarily by the oncological department. It is concluded that the spouses needed more support, wanted more information, and asked for the possibilities to talk about their emotional problems. This need is emphasized by the present strategy in the health system, where still more patients are treated on an out-patient basis. It is important that the professional support is offered from the time of the diagnosis. PMID- 8209407 TI - [Switching of the great vessels (arterial switch surgery) in transpositio vasorum]. AB - Since April 1992 the arterial switch operation (ASO) has been the treatment of neonates with transposition of the great arteries (TGA) at Rigshospitalet, Copenhagen. Thirteen mature neonates with TGA underwent ASO. Ten patients had simple TGA, two had TGA associated with a ventricular septal defect (VSD), and one had TGA with VSD and in addition moderate right ventricular hypoplasia. All patients survived the operation and are still alive. Perioperative bleeding was a problem in three cases. Eleven patients had an uncomplicated postoperative course. One patient had peri- and postoperative left ventricular failure and was reoperated after three months for a residual VSD. One child developed renal failure and needed peritoneal dialysis. The patients have been followed for 5.5 (range 0-12) months, they are all in good condition and thriving well. The presented early results after ASO justify continued recommendation of ASO as the operation of choice for TGA in neonates at Rigshospitalet. PMID- 8209408 TI - [Acute pancreatitis in Denmark]. AB - The incidence, etiology, severity and mortality of acute pancreatitis in Denmark were investigated by examining published material from Denmark from the period 1979-1992 and information from the central registry of diagnoses from the period 1981-1990. The incidence of acute pancreatitis increased from 26.8 to 35.4 per 100,000 inhabitants per year from 1981 to 1990. An increase in the incidence among males was solely responsible for this total increase in incidence. Acute pancreatitis is significantly more frequent in men than in women, in men the frequencies in the age-group 15-64 and the age-group > 65 were the same. In contrast, acute pancreatitis was nearly twice as common among women of 65 or older as it was among the 15-64 year-old women. Oedematous pancreatitis accounted for 95% of the total number of cases registered, with minimal yearly variations (94.0-96.0%). The total mortality was low, with no systematic variation in the period studied (3.2%, yearly variations between 2.6 and 4.2%). Hospitalization time decreased over the period from an average of 12.8 to nine days. PMID- 8209409 TI - [Clinical significance of changing from a second to a third generation thyroid stimulating hormone (TSH) assay]. AB - In recent years new sensitive immunochemoluminiscentic methods to measure thyroid stimulating hormone, TSH have been introduced. In this investigation we have made a comparison between an older, less sensitive, second generation TSH assay and a new, sensitive, third generation TSH assay in order to evaluate if new information of clinical value is obtained. We found that 20% of all the sera that were sent to the laboratory for TSH measurement showed low values. In the sera with low TSH concentration a great variation was observed between the "correct" values found with the third generation assay and the values found with the less sensitive second generation assay. We conclude, that since many sera sent to a routine laboratory have low TSH concentrations, and since it is of clinical importance to know the correct TSH value in many different patient categories, a third generation TSH assay is recommended in the daily routine. PMID- 8209410 TI - [Cystic adventitial degeneration. A rare cause of intermittent claudication]. AB - Cystic adventitial disease of the popliteal artery is an unusual condition of uncertain etiology in which a mucin-containing cyst forms in the wall of the popliteal artery and causes symptoms of intermittent claudication. The patient is typically a young non-smoking male, whose arteries otherwise are normal. Arteriography may show a smooth-walled narrowing or a non-specific complete occlusion, but may also be normal. Non-invasive imaging techniques may be helpful. We report two cases of cystic adventitial disease. Both were successfully operated on with resection of the diseased arterial segment and vein bypass interposition. PMID- 8209411 TI - [Is smoking more dangerous for women than for men?]. PMID- 8209412 TI - [Workload in emergency departments following new organization--uninteresting?]. PMID- 8209413 TI - [Treatment of benign recurrent goiter]. PMID- 8209414 TI - A comparison of methods for isolating plasmid DNA from Clostridium perfringens. PMID- 8209416 TI - Lungworms, maedi visna and mixed infections with respiratory viruses in Syrian Awassi sheep. PMID- 8209417 TI - A mechanical stimulator for the determination of the minimum alveolar concentration (MAC) of halothane in the rabbit. AB - The minimum alveolar concentration (MAC) of halothane was determined in New Zealand White rabbits. Tracheal anaesthetic concentrations were measured using a Siemens Servo Gas Monitor. A stimulator was used to deliver precisely controlled mechanical stimuli for the determination of MAC. Movement of the rabbit's head was recorded using a force transducer attached to the teeth. Evidence is presented that for the determination of MAC a precise nociceptive threshold is preferable to the so-called supramaximal stimulus used in clinical anaesthesia and in determination of anaesthetic potency. We conclude that techniques for the determination of MAC which disregard either sensitization of sensory mechanisms by producing tissue inflammation or the possibility of nerve compression by severe mechanical stimuli are of questionable value. The use of the mechanical stimulator described, or a similar device, would help in the standardization of the determination of MAC in all species by facilitating the application of a force of controlled amplitude, duration and velocity, thereby removing some of the variables which confound comparative studies of MAC. PMID- 8209415 TI - Creatine kinase in the dog: a review. AB - In the dog, creatine kinase (CK) is mostly present in the skeletal muscles, myocardium, brain and intestine. The MM isoenzyme predominates in muscles and myocardium. In plasma, reference values depend on the technique used and CK-MB accounts for about 30-45% of total CK activity. Sex has no influence on plasma CK activity, which is higher in young dogs than in adults. Plasma CK is elevated after physical exercise. After its release from the cells, CK reaches the plasma mostly via the lymphatic route and then remains in the plasma compartment. It is rapidly cleared with a half-life of about 2 hours. Muscle diseases are the main source of plasma CK elevations: inherited myopathies, malignant hyperthermia, hypothyroidism, vitamin E-selenium deficiency, prolonged decubitus, intramuscular injections, surgery, etc. Plasma CK is also increased in experimental myocardial infarction, for which the dog is an interesting model, allowing quantification of the damage by measuring the total CK activity released. PMID- 8209418 TI - Identification of metoclopramide metabolites in the urine of cattle by gas chromatography-mass spectrometry and high-performance liquid chromatography photodiode array detection. AB - The urinary metabolites of metoclopramide (4-amino-5-chloro-N-[2 diethylaminoethyl]-2-methoxybenzamide) were identified in cows. The drug was administered intravenously, voided urine was collected, and individual urine extracts were analysed by gas chromatography-mass spectrometry and high performance liquid chromatography-photodiode array detection. The parent compound and one major metabolite (4-amino-5-chloro-N-[2-(ethylamino)ethyl]-2 methoxybenzamide) were common to all individuals. In addition to the parent and major metabolite, a second, minor metabolite was identified in two cows as 4 amino-5-chloro-N-[2-(diethylamino)ethyl]-2-hydroxybenzamide. The identity of the minor metabolite was confirmed by comparison with a standard synthesized by a new method. Metabolite identification and characterization in food animal species allows the design of safety and environmental impact studies and relative metabolite ratios between dose treatment groups. PMID- 8209419 TI - Mapping of Marek's disease virus genome: identification of junction sequences between unique and inverted repeat regions. AB - Polymerase chain reaction (PCR) to amplify MDV DNA and subsequent sequencing identified the junction of TRL/UL, UL/IRL, IRS/US, and US/TRS. The TRL/UL junction is located 192 bp downstream of the last EcoRI site in the TRL region, while the UL/IRL junction is located 192 bp upstream of the first EcoRI restriction enzyme site in the IRL region. The IRS/US junction is located 950 bp downstream of the second EcoRI site in the IRS region, while the US/TRS junction is located 950 bp upstream of the first EcoRI restriction enzyme site in the TRS region. BamHI restriction enzyme mapping of one of the PCR products identified two novel DNA subfragments, BamHI-U2 and -P4, upstream of the US/TRS junction of the MDV genome. Sequencing of the BamHI-D fragment revealed a novel open reading frame (ORF) encoding a 155 amino acid protein. The TRL/UL junction is located in this ORF. The N-terminal 65 amino acids of this protein is homologous to the N terminal region of the previously reported pp38, which is located in the UL/IRL region. Computer-assisted analysis indicated that both are transmembrane proteins and that they share an antigenic domain. PMID- 8209421 TI - Studies on the antigenicity and nucleotide sequence of the rabies virus Nishigahara strain, a current seed strain used for dog vaccine production in Japan. AB - The Nishigahara strain of rabies virus, a current seed strain used for animal vaccine production in Japan, is believed to derived from the original Pasteur strain obtained from Paris in or before 1915. In Japan, the virus was serially passaged through several kinds of animals and cell cultures. Reactions with anti nucleocapsid protein monoclonal antibodies (MAb-N) indicated the Nishigahara strain had maintained the antigenic profile of the Pasteur virus. Reactions with monoclonal antibodies to the glycoprotein (MAb-G) revealed differences between the Nishigahara strain and the Pasteur strain; however, the Nishigahara strain maintained a closer resemblance to the Pasteur virus than to other Pasteur related viruses or to rabies strains unrelated to the Pasteur strain. Comparative amino acid sequence analysis of cloned cDNA encoding the G gene confirmed the antigenic differences among these strains and the resemblance of the Nishigahara strain to the original Pasteur strain. Comparative nucleotide sequence analysis of the noncoding pseudogene region (Tordo et al., Proc Natl Acad Sci USA 83, 3914 3918, 1986) revealed different relationships. Unlike the Pasteur strain, which encodes a transcription-terminating signal at the end of the G gene (marking the beginning of the pseudogene), a long G-L intergenic sequence in the Nishigahara strain was connected to the 3' end of the cDNA, and the transcription-terminating signal was present only at the end of, but not before, the pseudogene. These results are not inconsistent with the documented origin of the Nishigahara strain, but the genome structure around the pseudogene region suggests divergence from the Pasteur strain and a closer resemblance to other strains of rabies virus. PMID- 8209420 TI - Small RNA expression from the oncogenic region of a highly oncogenic strain of herpesvirus saimiri. AB - Herpesvirus saimiri induces acute lymphomas and leukemias in primates and rabbits. Sequence divergence of the right end unique region of the genome classifies virus strains into three groups (A, B, and C), and previous studies have demonstrated correlation between DNA grouping and oncogenicity. In order to relate different oncogenicity to the underlying molecular mechanisms, we reported earlier the expression of a bicistronic mRNA from the oncogenic region in a highly oncogenic group C strain, and the present study is the first report on small RNA transcripts from the same region. The transcripts and 6.2 kbp on the oncogenic region were sequenced and characterized. We show that four U-type small RNAs are expressed in tumor cells transformed by this strain, in contrast to the seven small RNAs reported from a weakly oncogenic group A strain. Sequence comparisons between the two strains showed that the right end region of strain 484-77 of group C is about 1 kbp shorter. The conserved 5' AUUUA repeats of some small RNAs, and their proposed implication in lymphokine mRNA stabilization, are also discussed. PMID- 8209422 TI - A preliminary translational map of the frog virus 3 genome. AB - A preliminary map of the frog virus 3 (FV 3) genome was constructed by hybridization-selection of mRNAs to cloned DNA fragments and translation in reticulocyte lysates. FV 3 mRNAs were hybridized to KpnI, HindIII, and SalI restriction fragments representing the entire FV 3 genome. Two different hybridization conditions were employed in order to discriminate between the hybridization of early and late mRNAs. A total of 43 major and 18 minor early genes and nine major and three minor late genes were mapped. A 24 kb region comprised of the KpnI D, H, and E fragments encodes 8 of the 12 late genes that were mapped. PMID- 8209423 TI - Open reading frames in a 4556 nucleotide sequence within MDV-1 BamHI-D DNA fragment: evidence for splicing of mRNA from a new viral glycoprotein gene. AB - A DNA segment of the MDV-1 BamHI-D fragment was sequenced, and the open reading frames (ORFs) present in the 4556 nucleotide fragment were analyzed by computer programs. Computer analysis identified 19 putative ORFs in the sequence ranging from a coding capacity of 37 amino acids (aa) (ORF-1a) to 684aa (ORF-1). The special properties of four ORFs (1a, 1, 2, and 3) were investigated. Two adjacent ORFs, ORF-1a and ORF-1, were found by computer analysis to have the properties of two introns encoding a glycoprotein: ORF-1a encodes an aa sequence with the properties of a signal peptide, and ORF-1 encodes a polypeptide with a membrane anchor domain and putative N-glycosylation sites in the aa sequence. ORF-1a and ORF-1 were found to be transcribed in MDV-1-infected cells. Two RNA transcripts were detected: a precursor RNA and its spliced form. Both are transcribed from a promoter located 5' to ORF-1a, and splice donor and acceptor sites are used to splice the mRNA after cleavage of a 71-nucleotide sequence. This finding suggest that ORF-1a and ORF-1 are two introns of a new MDV-1 glycoprotein gene. The DNA sequence containing ORF-1 was transiently expressed in COS-1 cells, and the viral protein produced in these cells was found to react with anti-MDV serotype-1 Antigen B-specific monoclonal antibodies. These studies indicate that the protein encoded by ORF-1 has antigenic properties resembling Antigen B of MDV-1. A gene homologous to ORF-1 was detected in the genome of both MDV-2(SB1) and MDV-3(HVT), which serve as commercial vaccine strains. Two additional ORFs were noted in the 4556 nucleotide sequence: ORF-2, which encodes a 333 aa polypeptide initiating in the UL and terminating in the TRL prior to the putative origin of replication, and ORF-3, which encodes a 155 aa polypeptide that is partly homologous to the phosphoprotein pp38 encoded by the BamHI-H sequence. The 65 N-terminal aa of the two gene products are identical, both being derived from the nucleotide sequences in the TRL and IRL, respectively. Additional homologous aa sequences are the hydrophobic aa domain in the middle of both proteins. The functions of ORF-2, ORF 3, and additional ORFs are under study. PMID- 8209424 TI - Detection of a 45 kD protein derived from the N terminus of the pea seedborne mosaic potyvirus polyprotein in vivo and in vitro. AB - A 45 kD protein (Pro1) derived from the N terminus of the pea seedborne mosaic potyvirus (PSbMV) polyprotein has been detected in extracts of infected pea plants and among in vitro translation products of PSbMV genomic RNA. The genomic region coding for the first 231 amino acids of the PSbMV polyprotein was cloned and expressed in Escherichia coli as a fusion protein with beta-galactosidase. A rabbit antiserum raised against the fusion protein recognized an approximately 45 kD protein in immunoblots of extracts of PSbMV-infected pea leaves that was not present in extracts of healthy leaves. The highest concentration of the 45 kD protein was found in extracts of young leaves, suggesting the protein may be rapidly degraded in vivo. After in vitro translation of PSbMV genomic RNA in a wheat germ extract, the antiserum immunoprecipitated a 45 kD polypeptide as well as some lower molecular weight translation products. On the other hand, an approximately 90 kD polypeptide was immunoprecipitated from in vitro translation products of genomic RNA in a rabbit reticulocyte lysate, corresponding to the combined molecular weights of Pro1 and the helper component predicted from genomic sequence data. PMID- 8209425 TI - Nucleotide sequence of RNA 3 of the British type isolate (Blencowe strain) of tomato aspermy virus. AB - The complete sequence of RNA 3 of the Blencowe, British (B) isolate of tomato aspermy virus (TAV) is presented. The RNA 3 of TAV-B is dicistronic, encoding the putative movement protein 3a and the capsid protein. PMID- 8209428 TI - [A method for transporting blood samples for the determination of antibodies to HIV infection]. AB - More than 80,000 blood samples are annually transported to the Lutsk diagnostic center for assessment of antibodies to HIV. A polystyrol container for 50 vials is used for transportation of the blood samples for these purpose. The advantages of this way of transportation are discussed. PMID- 8209426 TI - Cyclosporin A resistance of herpes simplex virus-induced "fusion from within" as a phenotypical marker of mutations in the Syn 3 locus of the glycoprotein B gene. AB - We here report research in which nine strains of Herpes simplex virus (HSV) with fusing activity were investigated in order to establish precise phenotypical markers of mutations in the carboxy terminus of glycoprotein B (gB). The gene region encoding the carboxy terminus of gB was isolated, then cloned, and finally sequenced. Our investigation showed that seven strains have different mutations in the syn 3 locus. We observed no base difference in the gB gene region encoding the carboxy terminus of gB of two other strains. Strains with a mutation in the carboxy terminus of gB induced fusion from within (FFWI) in the presence of Cyclosporin A (CyA) at a concentration up to 150 microM. There are two clusters of mutations correlated with the syn 3 locus and selected in the presence of CyA: One group comprised of amino acid substitutions at position 816, the other of changes at positions 853, 854, and 857. In contrast, the fusion induced by strains with mutations in other syn loci is CyA sensitive. CyA inhibits the FFWI at concentrations of 20-60 microM. The results demonstrate the CyA resistance of HSV-induced FFWI should serve as a phenotypical marker of mutations in the carboxy terminus of gB. Moreover, our investigations revealed that fusion from without (FFWO) does not always serve as a phenotypical marker of mutations in the syn 3 locus. On the one hand, all FFWO-positive strains possess a syn 3 locus mutation, whilst, on the other hand, five strains with mutations in the carboxy terminus of gB are FFWO negative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209427 TI - [Drug and non-drug immunocorrection in peptic ulcer]. AB - Drug immunocorrection and microwave resonance therapy allowed to normalize the immune status in 93% of patients with ulcer disease. This allowed to achieve clinico-endoscopic remission in 82%, reduce scarring time on the average by 6-7 days and to reduce markedly the recurrence frequency. PMID- 8209429 TI - [A long-term prospective observation of the course of dust-induced bronchitis in mechanical engineering workers]. AB - A study of 206 machine builders in dynamics (up to 15 years) with dust-induced bronchitis showed that the disease has a tendency to advancing within the first three years, especially in those with a combination of noxious professional factors (dust, heat, hard physical work). Negative risk factors: working conditions, preceding unspecific respiratory infections, smoking. PMID- 8209430 TI - [Martorell's syndrome]. PMID- 8209431 TI - [The atypical manifestation of lymphogranulomatosis and metachronous stomach cancer in a young female patient]. PMID- 8209432 TI - [Improvement in the management of medical care under the new economic conditions]. AB - The tasks of economic methods of medical care administration include a rigid mechanism uniting quality and scope of activities with the amount of economic stimulation. This ensures protection of the patients from inadequate medical care. Expertise control commissions are forms of moral and psychological training of medical personnel for work in conditions of budget-insurance medicine. PMID- 8209433 TI - [The importance of the scientific communication media in realizing the processes of innovation in public health]. AB - A questionnaire used was to evaluate the state of providing information, implementations of science achievements into medical practice, ways and methods of its adaptation under new economic condition. Discrepancies in current scientific communications and tendencies of development of a given domain of medicine were found. Respondents emphasized a low level of implementation of novelties into practice. Ways and methods of improving the situation are outlined. PMID- 8209434 TI - [The dynamics of the indices of mortality from ischemic heart disease in a large industrial center]. AB - It was found that the dynamics of mortality from ischemic heart disease showed a negative tendency among the population of Kiev as compared with urban population of other cities of Ukraine. An increase was noted of mortality among the workable population of Kiev and also of the non-hospital mortality. PMID- 8209435 TI - [Nikolai Ivanovich Morozkin (on the centenary of his birth)]. PMID- 8209436 TI - [The activities of Honored Physician of Ukraine Nikolai Sergeevich Bogdanov]. PMID- 8209437 TI - [Mercury technogenic pollution of the environment--a priority ecological hygiene problem (a review of the literature)]. AB - The authors analyze distribution of mercury in the contaminated zone depending on the chemical formula of mercury and routes of entry, enumerate the norm rating and indices to be used in ecologo-hygienic evaluation of the hazards degrees of the actual level of mercury in the water, atmospheric air and soil, describe numerous sources of technical solutions of reducing mercury entry to environment from technogenous sources. Modern achievements of science and technology make it possible to exclude entry of mercury and its compounds into the environment. PMID- 8209438 TI - [The risk assessment of the effect of anthropogenic chemical pollutants on the health of the population (a review of the literature)]. PMID- 8209439 TI - [The immunity status of the inhabitants of the city of Kiev 5 years after the accident at the Chernobyl Atomic Electric Power Station]. PMID- 8209440 TI - [The natural body resistance of the inhabitants of the city of Kiev subsequent to the accident at the Chernobyl Atomic Electric Power Station]. AB - A study carried out among residents of the city of Kiev indicates that combined chronic radiation after the Chernobyl accident in small doses resulted in a reduction of the natural killer activity level, decrease of the number of leucocytes, lymphocytes and in their qualitative disorders. With time after the Chernobyl accident there occurred a deterioration of the above values. PMID- 8209441 TI - [Changes in the status of the indices of the immune system in people after the accident at the Chernobyl Atomic Electric Power Station]. PMID- 8209442 TI - [The status of epidemiological surveillance in rickettsioses in Ukraine]. AB - A multi-annual study of rickettsiosis in the Ukraine is presented which included Brill's disease, Q-fever, Volyn fever. The status of epidemiological surveillance is outlined. Ways of perfection of the surveillance system are described. PMID- 8209443 TI - [The autoimmune changes in children living in areas contaminated by radionuclides after the accident at the Chernobyl Atomic Electric Power Station]. AB - A study of the blood sera of 50 children from the zone contaminated by radionuclides due to the Chernobyl accident was conducted to determine the immune status (level of immunoglobulin of Ig classes (A,M,G), presence of serum autoantibodies, determination of active anti-Sm antibody zones). A statistically valid increase of the IgM and IgG, reduction IgA levels was found. Antibodies to thyroid, smooth muscles, parietal cells, mitochondria were not found; 7% of patients showed autoantibodies to DNA and antinuclear factor. PMID- 8209445 TI - [The rehabilitation of duodenal peptic ulcer patients who participated in the cleanup of the aftereffects of the accident at the Chernobyl Atomic Electric Power Station]. AB - These patients require individual rehabilitation after determination of the unspecific reactivity of the body with prodigiosane. Depending on the results of this test the patients were treated with drugs stimulating the immune response in case of hyporeactivity, with adaptogens in normoreactive course of the disease and drugs modulating B-cell immunity in hyperreactivity. This approach allows to reduce hospital time, enhances remission. PMID- 8209444 TI - [The use of surface-active substances in a 30-kilometer area of the Chernobyl Atomic Electric Power Station]. AB - A study of dining enterprises and laundry shift-workers of the 30-km Chernobyl accident zone revealed that surface-active substances extensively used in the zone produced a negative effect on the body (irritation of the upper respiratory tract, skin, allergic reactions). Prophylactic measures and treatment of this category of workers are discussed. PMID- 8209446 TI - [The current principles in the conservative treatment of peptic ulcer patients]. PMID- 8209447 TI - [Current drugs in the treatment of bronchial asthma patients (a review of the literature with the results from the author's own research)]. PMID- 8209448 TI - [The sulfanilamide resistance of patients with type-2 diabetes mellitus]. PMID- 8209449 TI - [The prognosis of work capacity in patients with rheumatic defects after heart operations]. AB - A study of rheumatic patients after operations on the heart indicates that working capacity prognosis is determined not only by the severity of the somatic state but also by social and psychological aspects. The authors revealed sociopsychological and clinical prerequisites of high and low working adaptation that allow to make a concrete working prognosis and establish rehabilitation programs for the individual rheumatic patients undergoing heart surgery. PMID- 8209450 TI - [Changes in the central and intracardiac hemodynamics of patients with rheumatoid arthritis (an echocardiographic study)]. AB - It was found that rheumatoid arthritis patients with clinical signs of cardiac involvement showed significant changes of the central and intracardiac hemodynamics that were characterized by suppression of the contractile and pumping function of the left ventricle as compared with patients showing no heart involvement. The authors describe in detail special treatment of RA patients with cardiac involvement. PMID- 8209451 TI - [The clinical significance of determining sulfhydryl groups and succinate dehydrogenase in the peripheral blood lymphocytes of patients with liver and biliary tract pathology]. AB - It was established that patients with hepatobiliary pathology showed a reduction of SH groups and activity of lymphocyte succinate dehydrogenase of the peripheral blood. The level of this reduction depended on the severity of the pathological process and was lowest in viral hepatitis and cancer of the head of the pancreas. A dynamic study of SH groups and SDG in these groups of patients makes it possible to evaluate disorders of oxidation, oxidation, severity of the disease; it is also of prognostic significance. PMID- 8209453 TI - [Comparative data on the plating out of Mycobacterium tuberculosis on Samillo's modified FIN-11 medium and on the Lowenstein-Jensen and FIN-11 media]. AB - A modification of the Fin-114 medium is proposed where sodium glutaminate was substituted for a yeast autolysate and ammonium citrate for ammonium oxaacetate. The seeding of Mycobacteria tuberculosis was higher (3-4%) as compared with the two above media (2.4 and 2.6% respectively). PMID- 8209452 TI - [Extracorporeal shockwave lithotripsy in the treatment of gallstone patients]. AB - Stroke-wave lithotripsy (SWL) was used for the treatment of patients with cholelithiasis. Indications and contraindications were strictly observed. This method provides destruction calculi down to a size of 2-3 mm which enables them to enter the intestine without local injury. Subsequent choleritics, exercises, duodenal to reduce time of gallbladder emptying and intake of litholytics. PMID- 8209454 TI - [The information value of epidemiological research in chronic nonspecific lung diseases]. AB - Results of the study indicate that in several countries there occurred during 1971-1980 a reduction of mortality of the male population at the age of 1-4 years. In those over 65 years of age this index was inconsistent. Results indicate a definite dependence of mortality on age. PMID- 8209455 TI - [The role of echo scanning of the kidneys in the diagnosis of acute pyelonephritis]. AB - The role of echo scanning in the diagnosis of acute pyelonephritis was evaluated in 123 patients. It was established that ultrasonography in acute pyelonephritis is a highly informative diagnostic method. The importance is high in acute obstructive pyelonephritis and less informative in acute non-obstructive pyelonephritis. The method has no equal counterparts in the most difficult cases for diagnosis. Association of renal echo scanning with traditional method significantly increases the diagnosis quality. PMID- 8209456 TI - [The efficacy of heparin therapy in patients with diabetic glomerulosclerosis]. AB - Heparin therapy (25,000 U/day) of 38 patients with diabetic glomerulosclerosis resulted in improvement in 31 (82 +/- 6%). The treatment was not effective in 5% and complications were seen in 2 patients. Blood coagulation control is necessary during heparin treatment and turbidimetry proved to be highly informative in objective registration of coagulation and fibrinolysis processes. PMID- 8209457 TI - [The current problems of the viral contamination of the water environment (a review of the literature)]. PMID- 8209458 TI - [The use of radioactive phosphorus in treating epilepsy patients]. PMID- 8209459 TI - [The personality-modulated dissimulative behavior of patients with paranoid schizophrenia]. AB - The revealed variants dissimulation in 120 mental patients at initial stage of schizophrenia stimulated evaluation of premorbid personality changes and their significance in the formation of dissimulative tendencies. 63 patients showed reticence, 49--affective instability, 8--increased irritability and unmotivated mood changes. Comparative analysis of clinical variants of dissimulation with the aspects of personality permit to suggest their importance in formation of behaviour motives in the development of the schizophrenia process at the paranoia stage. PMID- 8209460 TI - [The efficacy of quercetin and tocopherol acetate in treating patients with Flexner's dysentery]. AB - Quercetin and tocopherol were given to 134 patients with Flexner's dysentery intramuscularly for 7 days; 154 patients received routine treatment. It was found that quercetin and tocopherol acetate enhanced normalization of clinical indices and restoration of the immune homeostasis. The above drugs are recommended for the complex treatment of dysentery. PMID- 8209461 TI - [Cross-reacting HLA antigens as a factor increasing the risk of childlessness in a family]. AB - A comparative analysis of HLA phenotypes of fertile and infertile spouses revealed that among the infertile the sum of spouses showed compatibility in two or three HLA antigens. A detailed analysis also showed that 10 infertile couples exhibited identical and 2 antigens with a similar structure and function with so called cross-reactions increasing the histocompatibility index to 75%. The significance of these facts for infertility risk factors is discussed. PMID- 8209462 TI - [The secondary prevention of arrhythmias in coal miners]. AB - For optimal treatment IHD complicated by ventricular extrasystoles (VE) in the course of ambulatory treatment with antiarrhythmic membrane-stabilizing drugs, the authors evaluated dosage, combinations of rhythmilen, ethacirine, ethmorin with allapinin and obtained a stable antiarrhythmic effect. The pathogenetic aspects of VE were considered. PMID- 8209463 TI - [The clofelin and nifedipine treatment of hypertensive crises in elderly patients]. AB - Simultaneous use of clophelin and nifedipine for hypertensive attacks in elderly subjects resulted in a sharp fall of the AP due to decrease of the cardiac ejection. In consecutive use of these drugs nifedipine was followed 2 hours later by clophelin in small dosterinemia and increase of cardiac ejection were observed. The consecutive method is ses and a prolonged reduction of AP, peripheral resistance, diastolic values, hyperaldo- preferred in the elderly patients. PMID- 8209464 TI - [The use of sodium nitroprusside aerosols combined with ultrasound in the combined treatment of patients with ischemic heart disease and heart failure]. AB - Use of sodium nitroprusside aerosol in association with ultrasound in 51 patients with IHD plus cardiac failure (stage I-IIA) allowed to reduce the dosage and side effects of drugs as compared with a group of patients by routine complex methods. The method may be used for treatment and prophylaxis of initial stages of cardiac failure in IHD patients including those with contraindications to cardiac glycosides. PMID- 8209465 TI - [Carbohydrate metabolism in patients with Itsenko-Cushing disease following the vascular-pedicle transplantation of the adrenal gland]. AB - The study was aimed at the evaluation of functional condition of pancreatic islet apparatus in patients with Cushing's disease who underwent adrenal microsurgical transplantation after bilateral adrenalectomy. The examination of 19 patients included immunological tests as well as calculation of insulin level increase, insulin ejection rate and insulin level excess over the baseline after glucose loading. The results suggest that patients with Cushing's disease in active stage reveal increased sensitivity to glucose and functional capacity of pancreatic beta-cells. After unilateral adrenalectomy insulin base level was observed to fall while increased beta-cells responsiveness to glucose remained unchanged. At the same time adrenal autotransplantation on the vascular stem in patients with the Cushing's disease resulted not only in normalization of insulin base level but also in the improvement of the functional indices of the islet cells. PMID- 8209466 TI - [The pathomorphosis of surgical thyroid diseases in the cis-Carpathians]. AB - The results of histological study of postoperative specimens obtained from 6,892 patients with diseases of the thyroid undergoing surgery at Lviv regional hospital from 1923 to 1990 were reviewed by means of IBM PC/AT-supported information system. The pathomorphism of surgical diseases of thyroid gland consists mainly in rise of their incidence peaking in 60s and 80s. For the years 1961-90 the rate of autoimmune lesions, adenomas and early forms of the thyroid carcinoma increased substantially. PMID- 8209467 TI - [The indices of the humoral immunity status and its correction in acute drug allergy in patients with the postthrombophlebitic syndrome of the lower extremities]. AB - The state of immunity was studied in 52 patients with the post-thrombophlebitic syndrome complicated by drug allergy. Levels of immunoglobulins G, A, M were found to be increased considerably in serum protein fractions. Series of medicamentous immunocorrective measures including removal of autoimmunoaggressive focus from altered area and surgical correction of venous blood circulation in damaged extremity was suggested. PMID- 8209469 TI - [The importance of the thermographic study method in oncology]. AB - Results of the study give reason to consider distant thermography a method for detection of a tumor and differential diagnosis of tumorous and inflammatory pathology. Registering changes of temperature in tumorous lesion, that is assessment of functional condition of pathological focus, may be helpful in solving diagnostic problems and provides possibility for monitoring of the process in the course of radiation therapy. PMID- 8209468 TI - [The determination of splenic mass by sonography]. AB - Sonographic determination of spleen mass by ultrasonic tomograph "Toshiba SAL 38AS" is suggested. The results of determination obtained in healthy persons and patients undergoing splenectomy with subsequent weighing of spleen demonstrated high accuracy of the method. Spleen mass in patients with hemoblastosis was revealed to be related closely to the degree of blastosis evaluated by hemo- and myelograms. PMID- 8209470 TI - [Myocardial infarct in youth: its etiology and morphogenesis]. AB - In the article on the grounds of 22,142 autopsy reports and 5,120 case histories retrospectively analyzed the hypothesis about the important role of chronic cumulative xenobiotic influence in the development and progress of myocardial infarction is substantiated. Spectral analysis of bones of deceased indicated significant increase of lead content in such patients. Morphological variants of coronary impairment were defined. Its morphogenesis was demonstrated to consist in formation of fibrotic, myoelastic and myofibrotic plaques and their subsequent fatty degeneration. PMID- 8209471 TI - [The risk factors for the occurrence of a first and a recurrent myocardial infarct in young people]. AB - 241 patients at the age of 22-41 with primary myocardial infarction (MI) and 51 patients who previously had recurrent MI have been examined. Rate of the principal generally accepted risk factors as well as blood group, professional, characterological, nutritional and other peculiarities being able to effect IM incidence were analyzed. The likelihood of primary and recurrent MI was found to be significantly connected with arterial hypertension (AH), hereditary burden, hypercholesteremia, stenocardia, astenoneurotic syndrome. The probability of myocardial infarction, especially of recurrent one, is increased in patients associating AH with stenocardia, hereditary burden with astenoneurotic syndrome, AH with hypercholesteremia, physical and nervous overstrain. PMID- 8209472 TI - [Cardiac hemodynamics in patients with ischemic heart disease combined with chronic cholecystitis]. AB - Cardiac haemodynamics have been studied radiocardiographically in 56 men at the age of 40-60 including 15 healthy persons, 24 patients with chronic coronary disease and 17 patients associating coronary disease with chronic cholecystitis. This association was shown to reduce minute heart volume thus playing the role of a factor compromising cardiac blood circulation in such patients. Neuroreflex influence on the coronary arteries and autoimmune damage of myocardium due to similarity of myocardial and gallbladder antigenic determinants may be probable mechanisms of such an effect. PMID- 8209473 TI - [A method for the differential diagnosis of chronic persistent hepatitis and liver cirrhosis]. AB - With a view to increase the accuracy of the differential diagnosis of chronic diseases of liver--chronic persistent hepatitis and initial manifestation of hepatic cirrhosis--the method based on the determination of general bactericidal activity of neutrophils is suggested. Cytochemical reaction on cationic proteins and nitroblue tetrazolium reduction with the blood of patients having the signs of liver lesion provide data for the calculation of the integral cytochemical activity of blood neutrophils. Values fluctuating from 4.0 to 6.0 indicate hepatic cirrhosis while their exceeding 7.0 may serve as an evidence of chronic persistent hepatitis. PMID- 8209474 TI - [The clinico-immunological efficacy of triacort in bronchial asthma]. AB - Efficacy of the home-made inhalant preparation "Tricort-aerosol" in 30 patients with moderate and severe bronchial asthma was assessed. Clinical, functional and immunological measures have been analyzed in the course of treatment with the drug. Administration of the drug in complex therapy was proved to be advisable in patients with different forms of bronchial asthma. PMID- 8209475 TI - [The significance of leukotrienes in the development of ventilatory and hemodynamic lung disorders in chronic obstructive lung diseases]. AB - 82 patients aging 18-67 with chronic obstructive lung diseases have been examined. The control group consisted of 35 healthy persons. Ventilation have been assessed by "stream-volume" technique, pulmonary blood circulation was studied rheopulmographically, the content of lipoxygenase metabolites of arachidonic acid (leukotrienes B4 and C4D4E4) was determined by radioimmunoassay. All the patients were divided into three groups with regard to the degree of respiratory and heart failure: the first group--moderate ventilatory disorders, the second group--pronounced respiratory and initial heart failure, the third one -severe respiratory and heart failure. The content of leukotrienes of all classes was found to be increased mainly in patients of the second and third groups. Circulatory disorders manifested in pre- and postcapillary pulmonary hypertension. Leukotrienes' level, pulmonary hypertension and the degree of ventilatory disorders correlated closely. PMID- 8209476 TI - [The characteristics of the urinary syndrome in patients with chronic glomerulonephritis]. AB - Quantitative measures of proteinuria, hematuria, lipoiduria and cylindruria have been studied in 156 patients with chronic glomerulonephritis in the course of long-term survey. The parameters evaluated and their combinations were noted to vary considerably. Proteinuria and/or hematuria not infrequently associated with cylindruria and/or lipoiduria were common in mesangioproliferative, mesangiocapillary and membranous glomerulonephritis. Patients with focal segmentary glomerulosclerosis-hyalinosis and minimal glomerulonephritis in the stage of remission revealed no pathological changes in urine. Statistically valid correlation was established between the degrees of proteinuria (as well as between those of lipoiduria) and proteinuria while there was no link between proteinuria and hematuria. PMID- 8209477 TI - [Experience in the correction of the internal picture of the disease in psychosomatic practice]. AB - Psychotherapeutic correction activated compensatory abilities in patients with schizophrenia and augmented antipsychotic effect of medicamentous treatment. Correction of the inner picture of disease and cultivation of sanogenetic intentions increased considerably the efficacy of therapeutic and rehabilitative measures both in psychosomatic and schizophrenic patients, shortened stay in hospital by 5-10 days, reduced morbidity with temporary loss of capacity for work by 10-15%. PMID- 8209478 TI - [The efficacy of the combined antibacterial treatment of patients with colonic cancer complicated by perifocal inflammation]. AB - In patients with colonic cancer complicated by inflammation since 1989 we have been using irrigations of tumor area with antibacterial drugs (dioxidin, betadin) side by side with conventional antibacterial and detoxicating therapy. The complex antibacterial therapy having been applied in 47 patients eliminated clinical manifestation of inflammatory process. Histological and morphometrical biopsy of tumor tissue and surrounding mucosa gives a reason to conclude that the complex therapy has proved to be effective. PMID- 8209479 TI - [The diagnosis and treatment of a malignant stomach ulcer]. AB - The results of treatment have been analyzed in 587 patients with stomach ulcer in 52 of whom ulcer was found to be malign. Methods of diagnosing of ulcer malignization are not reliable. Difficulties in differential histodiagnosis, absence of trustworthy diagnostic tests as well as advisability of additional mucus assays are underlined. The results of treatment depend on extension of the process and efficiency of the operation performed. In patients radically operated on for the process limited to gastric mucosa 5-year survival was 84.6%. PMID- 8209480 TI - [The determination of human IgM rotavirus antibodies in the blood serum by an immunoenzyme method in patients with a rotavirus infection]. AB - Rotavirus infection is one of the infectious diseases which can be verified only by a laboratory assay. That is why elaboration of new methods of the infection serodiagnosis is of great importance. Enzyme-linked immunoassay was worked up for IgM rotavirus antibodies detection in human blood serum. Validation of the method provides grounds for its being recommended for the diagnosis of rotavirus infection alongside with the determination of rotavirus antigens in feces. PMID- 8209481 TI - [The prevalence of iron-deficiency anemia among women working in the industrial enterprises of Poltava Province]. PMID- 8209482 TI - [The morphological changes in the body during overheating]. AB - Acute and chronic overheating causes considerable circulatory disorders in internals of experimental animals determined morphologically by systemic lesion of microcirculatory blood vessels. Acute overheating was established to be complicated by heatstroke manifesting in acute failure of vitals--lungs, brain and myocardium. Microcirculatory lesion in chronic overheating is caused by irreversible disorders of blood circulation, secondary hypoxic damage of organs and tissues with their functional failure. PMID- 8209483 TI - [The pharmacokinetics of hypotensive agents]. PMID- 8209484 TI - [The use of low-intensity laser therapy under sanatorium-health resort conditions in proctology patients]. AB - Use of helium-neon laser in complex treatment of patients with inflammatory processes of ano-rectal area was accompanied by anaesthetic effect and elimination of inflammation. Endoscopic laser therapy improved also colonic peristalsis. PMID- 8209485 TI - [Martorell's syndrome]. PMID- 8209486 TI - [A case of primary hyperparathyroidism]. PMID- 8209487 TI - [The importance of prophylactic fluorographic studies for the timely diagnosis of lung diseases]. AB - Analysis of the results of fluorographic screening of the population in the city of Kiev and Zaporozhye region suggests unadvisability of carrying out mass chest X-rays examination if the tuberculosis morbidity is less than 30 per 100,000. Also, prophylactic fluorography of the population being performed once in 2-3 years fails to ensure timely diagnosis of bronchitis, bronchiectasis and lung cancer. PMID- 8209488 TI - [Computer technology for the automatic processing of the physician's medical documentation]. AB - In the authors' opinion for a computerized health documents processing to be attractive for practitioners it should grant them appreciable advantages and not demand special training. When creating such a technology the authors achieved the object by as close as possibly adaptation of case history schemes to concrete diagnosis. The universal schemes are noted to be less convenient for the medical practice. PMID- 8209489 TI - [The social hygiene problems of the prevention of venereal diseases]. AB - The article is devoted to the questions of venereal diseases prophylaxis. The results presented allowed to elaborate united prophylactic system which includes different aspects of the problem. Complex prophylactic system worked up by the authors when implemented into public health practice yields exceptionally good results. PMID- 8209490 TI - [Preventable population mortality and an evaluation of the activities of the medical services]. AB - To estimate the effectiveness of health service activities and work of individual doctors the author suggests to analyze retrospectively avoidable mortality caused to a considerable extent by the drawbacks of medical care. Thorough analysis of such cases allows to work out prior measures on improvement of health service activities which is especially urgent under condition of its limited financing. Being compared to standards the results of the expertise give a possibility to determine the quality of medical care and provide grounds for differentiated remuneration of medical personnel. PMID- 8209491 TI - [High- amd low-molecular-weight heparins in clinical practice]. PMID- 8209492 TI - [Hemostatic disorders in connective tissue diseases]. PMID- 8209493 TI - [The status and means for improvement of the rheumatology service in Ukraine]. AB - Morbidity, prevalence, temporary loss of capacity for work and invalidity due to rheumatic diseases for the last 5 years in the Ukraine are analysed. Ways of further improvement of rheumatological service are determined. Aspects of coordinated approach to the solution of urgent rheumatological problems on the part of doctors working in different fields of medicine are discussed. PMID- 8209494 TI - [The morphofunctional aspects of the metastatic process in malignant tumors]. PMID- 8209495 TI - [The current problems of the combined action on the body of industrial, social and domestic factors (a review of the literature)]. PMID- 8209496 TI - [The blood kinin system in persons exposed to ionizing radiation as a result of the accident at the Chernobyl Atomic Electric Power Station]. AB - Condition of blood kinin system was studied in persons engaged on liquidation of Chernobyl accident sequels in 1986 and subjected to levels of ionizing radiation ranging up to 1 Gy. Activation of kininogenesis in such persons manifested in rise of the initial protaminolytic blood activity, partial decrease of prekallikrein level and imbalance on the part of the blood inhibitory potential in the form of alpha-2-macroglobulin level fall and increase of general blood antiproteolytic activity. PMID- 8209497 TI - [Changes in the drug-metabolizing function of the liver in chronic exposure of the body to low doses of ionizing radiation]. AB - When receiving sanatory treatment in Odessa persons residing at the areas with strict radioecological control (Chernigov, Zhitomir, Kiev Provinces) revealed deterioration of drug metabolism in liver. Experimental data indicated as well suppression of the microsomal drug-metabolizing system of liver caused by long term exposure of the body to low-dose ionizing radiation. The results obtained should be taken into consideration in such patients for the slowed down drug metabolism in liver may provoke side effects. PMID- 8209498 TI - [A method for studying the effect of social hygiene factors on the health of workers in industrial enterprises]. AB - The method suggested allows to study complex and separate influence of different socio-hygienic factors on workers' health. Determining the most essential factors and creating estimate prognostic tables on their basis make it possible to form risk groups and elaborate preventive programs. The method may be used in analogous studies of different groups of population. PMID- 8209499 TI - [Hygienic study of an activated fibrous charcoal material as a sorbing filtering element for drinking water afterpurification]. AB - The results of complex toxicological and hygienic study showed that the quality of pipe water filtered through the activated carbonic fibrous material (ACFM) "Dnepr-F" forming a part of absorptive filtering element improved markedly. The content of organic substances decreased drastically as well as that of nitrates and iron. Microbiological indices did not suffer appreciable changes and were within permissible limits. The water filtered through the absorptive element with ACFM had no adverse influence on the organisms of warm-blooded animals. Proceeding from foregoing one can conclude that the "Dnepr-F" may be recommended as a part of absorptive filtering element for the final refinement of drinking water. PMID- 8209500 TI - [Structural liver changes in myocardial infarct]. AB - Structural changes of liver have been studied in 20 patients who died of acute and recurrent myocardial infarction. Dystrophic, destructive, adaptive and compensatory changes of the liver may influence the choice of pathogenetic treatment of the disease. PMID- 8209501 TI - [The principles of administering drug and non-drug treatment methods in peptic ulcer]. AB - As the result of the study optimal schemes of the ulcer disease treatment were elaborated. They include microwave resonance therapy, immunomodulatory and antibacterial drugs with regard to localisation, depth and size of the ulcerous lesion, exacerbation rate, degree of secondary immune disorders and seeding of gastric mucosa with Helicobacter pylori. The treatment suggested allows to shorten the terms of ulcer cicatrization, reduces exacerbation rate and ensures clinico-endoscopic remission in most patients with ulcer disease. PMID- 8209502 TI - [Blood plasma cyclic nucleotides and compensatory-restorative processes in duodenal peptic ulcer]. AB - Contents of cAMP and cGMP in blood plasma as well as ratio cAMP/cGMP were studied by radioimmunoassay in 56 patients with duodenal ulcer of various severity. The examination was performed twice: before the treatment and 4 weeks after the treatment in a hospital. The analysis carried out with regard to the treatment efficacy in every variant of the clinical course of the disease showed that poor treatment results are associated with the dynamics of cyclic nucleotide (CN) plasma levels, especially with the increased ratio cAMP/cGMP, regardless of the disease severity which is characteristic of blood plasma CN taking part in compensatory-adaptive mechanisms in duodenal ulcer and evidences the necessity of differentiated approach to the treatment in accordance with developed adaptive reactions. PMID- 8209503 TI - [The relationship of duodenal peptic ulcer and gastroduodenitis to a chronic staphylococcal infection]. AB - Tonsillar and pharyngeal smears revealed growth of pathogenic microorganisms, mainly of Staphylococcus aureus, in 58.0 +/- 3.7% of 174 patients with duodenal ulcer and gastroduodenitis during remission or unstable remission, in 40.0 +/- 5.3% of 85 patients with other gastroenterological diseases and in 17.5 +/- 6.0% of 40 subjects constituting control group. Urease activity ratio (biological marker of Helicobacter pylori) was found to be approximately the same in every group of patients vs 11.1 +/- 6.2% of 27 healthy persons. Pathogenetic mechanisms of relation between duodenal ulcer, chronic gastroduodenitis and chronic focuses of infection are discussed. Lymphatic pharyngeal ring is supposed to be biotopical for Helicobacter pylori. PMID- 8209504 TI - [The immunomodulating effect of vilozen and splenin in the treatment of patients with acute and chronic toxic-allergic hepatitis]. AB - 65 patients with acute hepatitis and 116 patients with chronic hepatitis of toxico-allergic nature were examined. 20 patients with acute hepatitis and 40 patients with chronic form of the disease were prescribed in addition to conventional treatment 2-4 ml i.m. of splenin daily, 20 mg of vilosen daily in 3 4 divided doses in the form of 1% solution intranasally and the same quantity- sublingually. The drugs were administered for 10-15 days. Co-administration of splenin and vilosen was established to hasten normalization of clinical indices and immune homeostasis restitution thus advocating the use of the drugs as a part of therapeutic complex in the treatment of acute and chronic toxico-allergic hepatitis. PMID- 8209505 TI - [The characteristics of the immune status of patients with chronic obstructive bronchitis in PiM phenotypic variants of the alpha 1-proteinase inhibitor]. AB - The connection between alpha 1-proteinase inhibitor variants and immunity disorders in patients with chronic obstructive bronchitis is considered in the article. As a result of investigation disorders of both T- and B-immunity systems were found. They consisted in decrease of the content and proliferative activity of T-lymphocytes, changes in their populational composition, dysfunction of B lymphocytes, dysimmunoglobulinemia. These changes were more pronounced in allele M3+ carriers constituting the risk group on chronic lung diseases. PMID- 8209506 TI - [The air-blood barrier in chronic bronchitis deformans]. AB - The authors studied the aerohematic barrier (AHB) in chronic bronchitis deformans in 30 children. Lung fragments obtained during the operation were examined. A morphofunctional study in chronic bronchitis deformans with and without bronchiectasia revealed uniform changes of the capillaries and epithelial elements. The AHB showed also some different changes. Namely, vacuolization of endothelial cells and an increase of type II alveocytes with small osmophilic lamellar bodies were more pronounced in chronic bronchitis deformans. Changes in AHB elements may be caused by immature lung parenchyma and by compensatory processes directed for restoration of structures destroyed by the inflammatory process. PMID- 8209507 TI - [Paroxysmal tachyarrhythmias in patients with alcoholic heart lesions]. PMID- 8209508 TI - [The characteristics of the nephrotic syndrome in patients with renal amyloidosis]. AB - 68 cases of histologically confirmed renal amyloidosis associated clinically with the nephrotic syndrome (NS) were studied. The age of patients (over 40 years), mounting syndrome's manifestations in developing renal failure, absence of correlation between the quantity of amyloid deposits and completeness of the syndrome's picture were characteristic of the nephrotic syndrome in amyloidosis. NS in amyloidosis was most frequently the sign of extended process in kidneys and did not differ from other nephrotic syndromes by the disorders of lipid and protein metabolism. Direct correlation between nephrotic proteinuria and severity of tubulointerstitial lesions was found. 5-year survival from the onset of NS was 48%. Vital verification of NS caused by amyloidosis is complicated, nephrobiopsy being the most informative. PMID- 8209509 TI - [The significance of lipid peroxidation in the chronicity of glomerulonephritis with a hematuric component]. AB - Measures of lipid peroxidation (malonaldehyde contents in blood, erythrocyte membranes and urine), parameters of the antioxidant system, structural and functional indices of cell membranes (cholesterol level, general content of phospholipids and phospholipid spectrum) were studied in patients with acute and chronic (stable and advancing) hematuric glomerulonephritis. Glomerulonephritis chronization was established to be associated with the activation of lipid peroxidation, predominantly on the level of damaged organ, while the condition of the antioxidant system showed a trend to normalization. Advancing glomerulonephritis when compared to stable one revealed more pronounced processes of membrane destabilization as well as accumulation of lipid peroxidation products in membranes, erythrocytes, blood plasma and urine. PMID- 8209510 TI - [The psychoneurological status of psychics]. AB - It was established that 2/3 of extrasenses sustained head injury, clinical death etc. The same ratio are left-handed. It is this group that show the deja vu phenomenon and abnormal orientation in time and space. It is suggested that in several subjects organic lesions of the brain do not result in neurological deficit, but create preconditions for the appearance of extrasensory capabilities in the victims. The necessity is postulated for a detailed and mass screening of extrasenses by neurologists that may create a basis for scientific elaboration and understanding of this complex, interesting and unclear phenomenon. PMID- 8209511 TI - [The epidemiological and clinical characteristics of campylobacteriosis in Ukraine]. AB - Clinical course and epidemiological features of campylobacteriosis in Ukraine are described. The disease accounts for 11.2% of the total number of acute enteric infectious cases. Ratio of bacterial contamination of hens and their role in spread of campylobacteriosis have been established. Possible ways of transfer of the infection are discussed. PMID- 8209512 TI - [The therapeutic efficacy of reaferon in meningoencephalitis]. AB - There have been under observation 63 patients with meningoencephalitis at the age of 15-52 years whose complex treatment included reaferon and 42 patients with the same disease who were not given the drug. Reaferon was noted to be effective in meningoencephalitis. It shortened the period of clinical manifestation of the disease, hastened sanation of the liquor, influenced beneficially interferon production and modulated activity of the natural killers. PMID- 8209513 TI - [Brain function in diabetics]. AB - Nervous system lesion is a frequent complication of diabetes mellitus. The article presented quantitative characteristics of the bioelectrical activity of the brain and analyzes integrative frequency parameters of electroencephalogram. Functional indices of brain were shown to be worsened in diabetics as compared to healthy persons. The changes in bioelectrical activity of the brain were found to be more pronounced in patients with longer history of the disease as well as in those who had specific diabetic microangiopathies. The EEG parameters in patients with insulin-dependent diabetes mellitus were poorer than in persons suffering from non-insulin-dependent form of the disease. Features of the functional brain disorders in diabetes are discussed. PMID- 8209514 TI - [A comparative physiological hygiene evaluation of the technology for using pesticides in hothouse vegetable growing and floriculture]. AB - On the grounds of physiological and hygienic studies comparative estimation of working conditions and functional state of workers' organisms is presented with regard to technologies used in hothouses. It was established that in assessment of professionally conditioned hazard not only the level of chemical substances (pesticides content in the air of working zone, quantities of preparations in skin wash-outs) but also the total duration of contact with xenobiotics matter. Complex of methods including detection of possible specific pesticide influence and tests reflecting general state of the body is suggested for use in clinical and hygienic investigations. Personal professional registers containing data on duration of work with toxic substances are recommended. PMID- 8209515 TI - [The content of free amino acids and biogenic amines in the urine of hypertension patients]. AB - Contents of free amino acids and some biogenic amines were studied in hypertonic patients at the age of 40-50 years. The study demonstrates quantitative changes in levels of free amino acids and some biogenic amines caused by disorders of protein metabolism. The data obtained may be used for diagnosis of hypertonic diseases. PMID- 8209516 TI - [Myxoma of the heart: aspects of its histogenesis]. AB - 15 cases of heart myxomas are presented. Their origin from remains of embryonal mesenchymal tissue is hypothesized. Predominant localization at the foramen ovale area, where remains of embryonal tissue can be found, and peculiarities of histological structure resembling embryonal mesenchyma may be proofs of the hypothesis. Microscopic structure of myxomas is homogeneous: branching cells of histiocytic origin amidst basophilic or eosinophilic stroma presented by myxoid tissue, capillaries and vessels of various gauges at different stages of functional activity (shut-down, compressed, dilated, filled with erythrocytes). PMID- 8209517 TI - [The diagnostic aspects of intragastric pH measurement]. AB - The article presents results of the study of gastric acidity by intragastric pH metry in 255 patients, in 62 of whom (27.5%) it appeared to be normal. Hyperacidity was revealed in 100 patients (44.5%). The remaining 63 patients (28%) showed decreased gastric acidity. Diagnostic aspects of the method in examination of gastroenteric patients are considered. PMID- 8209518 TI - [Ionizing radiation and the blood kinin system]. PMID- 8209519 TI - [The gastroenterorenal interrelationships after a single intake of naftusia mineral water]. AB - Clinico-pathophysiological study revealed both reciprocal and direct relations between gastric and renal reactions on "Naftusia". Gastric secretion and diuresis changed in different directions in urological patients and paralleled in gastro enterological pathology. Correlation between terms of "Naftusia" evacuation from stomach and intestinal absorption of xylose on one side and intensity of diuresis on the other was direct but unsignificant. Direct significant correlation between the influence of "Naftusia" on xylose excretion and diuresis was established. PMID- 8209520 TI - [The characteristics of aerophagy and its treatment]. AB - Clinical and roentgenological examination of esophagus and cervical spine were carried out in 27 patients with functional aerophagia. In 11 of them the air was found to pass through without any swallowing into the stomach and in remaining 16 -into esophagus. All the patients revealed osteochondrosis, unstable and blocked spines. Manual therapy applied to cervical zone of spine promoted elimination of aerophagia. PMID- 8209521 TI - [The peripheral blood lymphocytes in patients with autoimmune thyroiditis]. PMID- 8209522 TI - [The characteristics of the current status of urologic cancer diseases (based on data from an interdistrict urology department)]. AB - Oncourological morbidity for the last 2 years according to data of inter-district urological department is considered in the article. Ratio of oncological patients has risen end equals 5-6% of total urological contingent, cohose rejuvenation cannot but draw attention. Cancer of prostate dominates in morbidity structure accounting for 1.2-2.5% of urological cases. It is followed by bladder cancer diagnosed in 2% of urological in patients. Tumors of testicles affecting young subjects aging from 25 to pathology. 35 have got more frequent. All the aforementioned explains the necessity of more detailed examination of urological patients for the early detection of oncological PMID- 8209523 TI - [The importance of the internal picture of the disease for the rehabilitative prognosis in paranoid schizophrenia]. AB - Clinico-catamnestic analysis of internal picture of disease was carried out in 237 patients with paranoid schizophrenia. High ratio of anosognosia (52%) was found. As many as 11% of patients aimed at overcoming morbid symptoms. PMID- 8209524 TI - [Acute hepatorenal failure occurring after taking rifampicin]. AB - A case of acute hepato-renal failure which developed after the oral intake of rifampicin is reported. Allergic reaction on the drug was accompanied by chill, weakness, paraesthesia, skin itch and facial swelling. The case described in the article appears to be all the more interesting due to the fact that severe lethal complication has developed in patient who had a history of allergic reactions on rifampicin. PMID- 8209525 TI - [The clinical picture, diagnosis and treatment of chronic liver diseases (a lecture)]. AB - The lecture is devoted to the important scientific trends in study of chronic liver diseases (CLD): pathomorphosis, the role of slow viruses and immunity in the pathogenesis. Three main genetically closely interlinked forms of CLD- hepatitis, hepatosis, cirrhosis--are considered. Principal methods of treatment in various forms of CLD are also described. The conclusion about necessity of further exploration of the problem is made. PMID- 8209526 TI - [The organization of professional orientation work at the precollege stage]. PMID- 8209528 TI - [The scientific information potential of the public health system in Ukraine: the problems and the means for their resolution]. PMID- 8209527 TI - [Reperfusion arrhythmias: the theoretical prerequisites and clinical aspects (a review of the literature)]. PMID- 8209529 TI - [The functional morphology of the thrombocytes and their role in the pathogenesis of atherosclerosis and ischemic heart disease (a review of the literature)]. PMID- 8209531 TI - [The use of thermographic study in urinary system diseases (a review of the literature)]. PMID- 8209530 TI - [Connective tissue function in diseases of the digestive organs (a review of the literature)]. AB - Review of the literature presented deals with the state of connective tissue and some aspects of its metabolism in ulcer disease, chronic gastritis, chronic hepatitis, hepatic cirrhosis, acute and chronic pancreatitis. Disorders of synthesis and degradation of collagen, changes in metabolism of glycosaminoglycans, glycoproteins and aminoglycans are described, their pathogenetical role in development end exacerbation of diseases of digestive organs is demonstrated. PMID- 8209532 TI - [Memory disorders in exposure of the body to drugs (a review of the literature)]. PMID- 8209533 TI - [Left ventricular function in patients with dilated cardiomyopathy]. AB - Functional state of left ventricle was studied in 43 patients with dilated cardiomyopathy. All the patients showed pronouncedly reduced total ejection, stroke volume and cardiac index, increased final diastolic and final systolic volumes, decreased ejection rate indices. Analysis of regional contractility of left ventricle allowed to detect significant fall of ejection fraction in 96.3% of segments. Diastolic dysfunction was characterized by disorders of isovolumetric relaxation, changes in hemodynamical structure and contribution of atrial systole to ventricular filling, decrease of volumetric compliance of left ventricle. The data obtained give a reason to consider that appropriate therapy of dilated cardiomyopathy should be carried out with taking into account both systolic and diastolic left ventricle dysfunction. PMID- 8209534 TI - [A rapid turbidimetric micromethod in the determination of hemostatic and fibrinolytic disorders in arterial hypertension patients of different ages]. AB - Disorders of haemostasis and fibrinolysis were studied in 54 patients of various age with arterial hypertension by turbidimetric express micromethod. Activation of coagulative system and inhibition of fibrinolytic activity tending to get more pronounced with age were found in patients with hypertonic disease at II stage and systolic arterial hypertension. Turbidimetry has considerable advantages: it can be performed rapidly, requires as much as 0.1 ml of plasma for the assay and provides complete information about the state of haemostasis and fibrinolysis. The method may be important in detecting minor signs of disseminated intravascular coagulation in patients with hypertonic disease. PMID- 8209535 TI - [The health status of the population after the accident at the Chernobyl Atomic Electric Power Station (based on data from Kiev Province)]. AB - Since the Chernobyl accident health of the population at Kiev region, especially of children, has deteriorated considerably. The number of healthy persons has decreased. There is a strong tendency toward accumulation of chronic nonspecific diseases among the population. After the disaster thyroid pathology, chiefly early thyroid carcinoma, has been observed to rise. Determination of radiative load on the thyroid is one of the main problems of liquidation of medical sequels of the accident. Calculation of dose load should be carried out with taking into consideration not only contribution of 131I, but also dose received at the account of other iodine isotopes as well as of isotopes of other elements getting into the body by gastro-intestinal and respiratory tracts. When analyzing thyroid morbidity one should take into account state of other organs and systems at the level of integral body. PMID- 8209536 TI - [The activity of the antioxidant system and membrane lipid peroxidation in hypertension patients]. AB - With the view to study state of antioxidant protection and membrane lipid peroxidation (LPO) in hypertonic disease (HD) 200 patients with HD of I and II stage (WHO classification) were examined. Structural and functional state of myocardium was assessed echocardiographically. Enzymatic and non-enzymatic LPO, catalase and superoxide-dismutase activity were analyzed in erythrocytes. Destabilization of cell membranes due to LPO activation and alteration of antioxidant potential established in patients with HD was paralleled by the degree of left ventricle hypertrophy. PMID- 8209537 TI - [The endolymphatic therapy of patients with suppurative cholangitis (1)]. PMID- 8209538 TI - [The endolymphatic therapy of patients with suppurative cholangitis (2)]. PMID- 8209539 TI - [Stomach and duodenal ulcers in middle-aged and elderly persons (clinico pathomorphological parallels)]. PMID- 8209540 TI - [The clinico-immunological efficacy of paspat and prodigiozan in the combined treatment of infectious-allergic bronchial asthma]. AB - 64 patients with infectious-allergic bronchial asthma (IABA) were examined. 20 of them were co-administered paspat, 24 patients additionally received prodigiosan, 20 patients constituted control group and were given conventional treatment. Patients of all the groups were comparable in age, state of immunological reactivity of the body and severity of the disease. Immunomodulatory effect of the drugs, mainly of paspat, not only resulted in normalization of functional properties of granulocytes but also promoted liquidation of quantitative and functional IABA-conditioned immunodeficiency on the part of T- and B-lymphocytes, thus increasing effectiveness of the treatment in the whole. PMID- 8209541 TI - [The effect of ultraviolet-irradiated blood on bronchial hyperreactivity in bronchial asthma patients]. AB - Clinical investigation was carried out with the view to study the effect of ultraviolet-irradiated autoblood on bronchial spasm induced by acetylcholine in 11 patients with moderate and severe bronchial asthma in out-of-attack period. Reinfusion of autoblood was established to reduce bronchial hyperresponsiveness in asthma thus allowing to control one of the main pathogenetical mechanisms. PMID- 8209543 TI - [The prognostic role of complement activity in hemoblastoses]. AB - Complement activity (CA) was studied in 40 patients with acute leukosis, in 75 patients with chronic myeloblastic leukosis and in 28 patients with multiple myeloma. Results indicated that unchanged CA was associated with a usual clinical course of the diseases, its fall resulted in infectious inflammatory diseases while increase of complement activity was characteristic of leukosis exacerbation. PMID- 8209542 TI - [The clinico-pathogenetic role of the eicosanoid system in pulmonary tuberculosis]. AB - Contents of leukotrienes B4, C4, C4/D4/E4, prostaglandins E and F2a, thromboxane B2 and 6-keto-PgF1a were studied by radioimmunoassay in patients with fresh and chronic pulmonary tuberculosis. Eicosanoids were established to take an active part in pathogenetical mechanisms of tuberculous process. Local forms of the disease were characterized by moderately risen level both of leukotrienes and prostaglandins. Freshly detected disseminated destructive process was accompanied by increased activity mainly of LtC4, LtC4/D4/E4 as well as of prostacyclin thromboxane system and PgF2a. Advance of pulmonary tuberculosis was associated with activated LtB4 and TxB2 synthesis and decreased production of PgI2, PgE, LtC4, LtC4/D4/E4. PMID- 8209544 TI - [A retrospective analysis of the efficacy of the heparin therapy of glomerulonephritis patients]. AB - Retrospective analysis of heparin efficacy (25,000 IU daily for 3 weeks) was carried out in 59 patients with different morphological and clinical forms of glomerulonephritis. The treatment proved to be effective in 32.2% of patients. Among unsuccessfully treated patients those with severe clinical and morphological forms prevailed. Indication for administration of heparin were specified. Disappearance of fibrin/fibrinogen degradation products from urine or fall in their level by 50% or more a week after the start of heparin were considered prognostically favourable. Graphical turbidimetry is recognized to be the best method of haemostasis monitoring during heparin therapy. PMID- 8209545 TI - [A comparative evaluation of the subfractional composition of the blood plasma by using laser correlation spectroscopy in orthopedic-traumatological diseases]. AB - Analysis presented by the authors confirms that laser correlative spectroscopy may be in principle a method for a study of plasma homeostasis on subfractional level in various orthopedic and traumatological diseases. The method allows to assess changes in the inner environment of the body with regard to diversity of structural and functional reorganization induced by various pathological processes. PMID- 8209546 TI - [The causes of disability in injuries to the locomotor apparatus]. AB - Statistical data for the period from 1985 to 1990 showed rise of primary invalidity due to traumas in most regions of the Ukraine. Taking into consideration the ratio of fractures in trauma structure we have analyzed invalidity on account of this kind of pathology. Retarded consolidation, multiple fractures and spine fractures are the main causes. Men aged below 45 prevailed among invalids. In 25.2% of invalids consolidation of both closed and open fractures was complicated by osteomyelitis. The second invalidity group was established in most cases (75.1%). This figure corresponds to mean statistical data in the Ukraine. PMID- 8209547 TI - [The Staphylococcus aureus carrier state among the workers of a machine-building plant]. AB - 120 workers of beet-harvesting combines plant and 120 students and teachers (control group) were examined for S. aureus carrying. In workers level of carrying on nasal and pharyngeal mucosa as well as on the skin of hands was 3-7 times as high as in members of control group. Number of carriers and quantity of microbial population on the skin of hands depended on the use of oils and emulsion in production process. Contact with oils favoured skin contamination while emulsions reduced bacterial colony. 36% of mechano-assembly shop workers and 10-12% of those employed at mechano-processing constitute the risk group which is likely to develop purulent skin diseases in microtraumas of hand and fingers. PMID- 8209548 TI - [Effect of L-isoleucine and glycine on catechol 2,3-dioxygenase expression and excretion in Escherichia coli]. AB - The secretion of gene products expressed in E. coli is a problem noticeable nowadays. Effect of glycine and L-Isoleucine on catechol 2,3-dioxygenase (CatO2ase) expression and secretion was reported here. Both L-Ile and Gly could increase CatO2ase production. Gly could also cause expressed product excreted into the culture medium. The effect of Gly and L-Ile was related to the composition of culture medium, the concentration of Gly and L-Ile and the culture time. The sensitivity to lysozyme of bacterium cells grown in the Gly containing medium was a little higher and electron micrograph of bacteria grown in the Gly containing medium showed morphological changes of cell wall and outer membrane. This may have been due to interference with peptidoglycan synthesis by the Gly, and cause passability increase, as reported in other bacterium strains. PMID- 8209549 TI - [Amplification of 16S rDNAs from halobacteria by means of PCR technique]. AB - The 16S rDNAs have been amplified from four halobacteria Haloarcula vallismortis (EM201), Haloferax denitrificans (EM303). A5 and B2 through a set of specific primers using the PCR technique. The molecule of the PCR products is about 1.47 kb. The hybridization results also show that these PCR products have DNA homology with halobacteria. PMID- 8209550 TI - [Isolation and identification of an oxygen-tolerant strain of Bifidobacterium from human feces]. AB - This paper reports 136 strains suspected to be species of the genes Bifidobacterium isolated from adult human faeces. Through detection of the ability to tolerate molecular oxygen in cultural environments, we obtained an oxygen-resistant strain TQ21-2-2 according to the Bergy's manual. It was identified as Bifidobacterium longum. A limited number of drinking the beverage, the experiments also using this strain in milk as a starter revealed that this strain has been found useful for treating cases with constipation. PMID- 8209551 TI - Congenital constriction band syndrome. Pathophysiology and treatment. AB - The clinical manifestations of 88 children with congenital constriction band syndrome involvement of the hand were reviewed. Seventy-five of these children had evidence of digital or limb amputations, with 235 upper limb amputations and 138 lower limb amputations. In the hand, digital amputations were most common in the index, middle, and ring fingers, whereas in the foot, amputations of the hallux were most often noted. Band indentation was often present at multiple levels. Proximal bands may be associated with neural compression. Syndactyly was invariably associated with a proximal interdigital sinus or cleft and was frequently associated with distal amputation. Examination of a 27-week gestation stillborn specimen having manifestations of congenital constriction band syndrome demonstrated the intrauterine biologic response to band constriction. The variable clinical manifestations of congenital constriction band syndrome can best be explained as the response of the growing, embryologically defined limb to intrauterine deformation or band-induced compression and ischemia. PMID- 8209552 TI - A defect-in-continuity in the canine femur: and in-vivo experimental model for the study of bone graft incorporation. AB - The in-vivo study of bone graft incorporation has traditionally used a segmental diaphyseal bone defect. This model reliably produces a nonunion, but is complicated by graft instability and altered limb loading stresses. The authors discuss the advantages of a defect-in-continuity canine femur model which produces a more consistent union with fewer mechanical complications despite the absence of fixation. This proposed model permits analysis of radiographic, histologic and biomechanical data which are more applicable to the usual clinical setting in which bone graft is required. PMID- 8209553 TI - Cervical spondylotic myelopathy: a review of surgical indications and decision making. AB - Cervical spondylotic myelopathy (CSM) is frequently underdiagnosed and undertreated. The key to the initial diagnosis is a careful neurologic examination. The physical findings may be subtle, thus a high index of suspicion is helpful. Poor prognostic indicators and, therefore, absolute indications for surgery are: 1. Progression of signs and symptoms. 2. Presence of myelopathy for six months or longer. 3. Compression ratio approaching 0.4 or transverse area of the spinal cord of 40 square millimeters or less. Improvement is unusual with nonoperative treatment and almost all patients progressively worsen. Surgical intervention is the most predictable way to prevent neurologic deterioration. The recommended decompression is anterior when there is anterior compression at one or two levels and no significant developmental narrowing of the canal. For compression at more than two levels, developmental narrowing of the canal, posterior compression, and ossification of the posterior longitudinal ligament, we recommend posterior decompression. In order for posterior decompression to be effective there must be lordosis of the cervical spine. If kyphosis is present, anterior decompression is needed. Kyphosis associated with a developmentally narrow canal or posterior compression may require combined anterior and posterior approaches. Fusion is required for instability. PMID- 8209554 TI - Internal fixation of pilon fractures of the distal radius. AB - When closed manipulation fails to restore articular congruity in comminuted, displaced fractures of the distal radius, open reduction and internal fixation is required. Results of surgical stabilization and articular reconstruction of these injuries are reviewed in this retrospective study of 49 patients with 52 displaced, intra-articular distal radius fractures. Forty-three patients (87%) with a mean age of 37 years (range of 17 to 79 years) were available for evaluation. The mean follow-up time was 38 months (range 22-69 months). When rated according to the Association for the Study of Internal Fixation (ASIF), 19 were type C2 and 21 were type C3. We devised an Injury Score System based on the initial injury radiographs to classify severely comminuted intra-articular fractures and to identify those associated with carpal injury (3 patients). Post operative fracture alignment, articular congruity, and radial length were significantly improved following surgery (p < .01). Grip strength averaged 69% +/ 22% of the contralateral side, and the range of motion averaged 75% +/- 18% of the contralateral side post-operatively. A combined outcome rating system that included grip strength, range of motion, and pain relief averaged 76% +/- 19% of the contralateral side. There was a statistically significant decrease in the combined rating with more severe fracture patterns as defined by the ASIF system (p < .01), Malone classification (p < .03), and the Injury Score System (p < .001). The Injury Score System presented here, and in particular the number of fracture fragments, correlated most closely with outcome of all the classification systems studied. Operative treatment of these distal radius fractures with reconstruction of the articular congruity and correction of the articular surface alignment with internal fixation and/or external fixation, can significantly improve the radiographic alignment and functional outcome. Furthermore, the degree to which articular stepoff, gap between fragments, and radial shortening are improved by surgery is strongly correlated with improved outcome, even when the results are corrected for severity of initial injury, whereas correction of radial tilt or dorsal tilt did not correlate with improved outcome. PMID- 8209555 TI - Development of the cartilage canals and the secondary center of ossification in the distal chondroepiphysis of the prenatal human femur. AB - The cartilaginous epiphysis of the distal femur is vascularized by a network of cartilage canals during prenatal development. The vascular invasion of the epiphysis begins at approximately eight to ten weeks of gestation with the initiation of cartilage canal formation. A complex vascular system develops within the canals and is well defined by fourteen weeks of gestation. The vascular system is fully developed several months prior to the development of the secondary center of ossification. The formation of the secondary center of ossification within the distal femoral epiphysis is preceded by changes that occur simultaneously within both the chondrocytes in the central portion of the epiphysis and the vascular and perivascular elements contained within the cartilage canals in the central portion of the epiphysis. These concurrent changes in the cellular morphology of the central chondrocytes and in the cellular structure of the central cartilage canals appear to be linked with the initiation of the process of osteogenesis. PMID- 8209556 TI - Struthers' ligament and associated median nerve variations in a cadaveric specimen. AB - A Ligament of Struthers has been identified and studied in a cadaveric arm. Its relationships to a rudimentary supracondylar process, the pronator teres muscle, the median nerve, and the medial epicondyle of the humerus are described. Compared to an extensively studied series of normals, the ligament in this case was associated with abnormally proximal branching of the median nerve, a finding which is surgically significant and not addressed in the literature to date. PMID- 8209557 TI - Differential diagnosis in patients with disorders of the patellofemoral joint. AB - Anterior knee complaints are difficult diagnostic problems. It cannot be overstated that the most important information available is to be found in the patient's history. Onset, quality, and quantity of symptoms must be assessed. This information is then synthesized to determine the specific functional disabilities resulting from the patient's anterior knee disorder. Once a history is obtained, a consistent, methodical physical examination can be performed to narrow the differential diagnosis. Radiographic evaluation is used to further hone the differential or to confirm the most likely diagnosis. Ultimately, a specific working diagnosis is selected and treatment is tailored to changing the underlying structural or biomechanical abnormalities that led to the patient's complaints. PMID- 8209558 TI - The pathology of acute chondro-osseous injury in the child. AB - Skeletal tissues from children sustaining acute skeletal trauma were analyzed with detailed radiologic and histologic techniques to assess the failure patterns of the developing skeleton. In the physis- and epiphysis-specific fracture propagation varied, usually going through the portion of the hypertrophic zone adjacent to the metaphysis. However, the physeal fracture in types 1 and 2 sometimes involved the germinal zone. There may also be microscopic propagation at oblique angles from the primary fracture plane, splitting cell columns apart longitudinally. The cartilage canals supplying the germinal zone appear to be "weak" areas into which the fracture may propagate, especially in infancy. Incomplete type 1 physeal fractures, which cannot be detected by routine radiography, may occur. Types 1, 2, and 4 physeal injuries may be comminuted. In type 3 injuries, discrete segments of physis that include the germinal zone may "adhere" to the metaphysis, separating the cells from their normal vascularity. In types 2 and 3, comminution may occur at the site of fracture redirection from the physis. Direct type 5 crushing of the physeal germinal zone does not occur, even in the presence of significant pressure-related changes within other areas of the epiphysis. Type 7 separation between cartilage and bone at any chondro osseous epiphyseal interface may occur, but is similarly impossible to diagnose radiographically. In the metaphysis torus, fractures result from plastic deformation of the cortex, coupled with a partial microfracturing that may be difficult to visualize with clinical radiography. Some of the energy absorption may also be transmitted to the physis, causing metaphyseal hemorrhage adjacent to the growth plate and variable microscopic damage within the physis. In the diaphysis, the greenstick fracture is associated with longitudinal tensile failure through the developing osteons of the "intact" cortex. The inability of these failure patterns to "narrow" after the fracture force dissipates is the probable cause of retained bowing (plastic deformation). In both torus and greenstick fractures, the fractured bone ends show micro-splitting through the osteoid seams. In the diaphysis, metaphysis, and epiphyseal ossification center there may be areas of focal hemorrhage and microfracture that correlate with the reported MRI phenomenon of "bone bruising." Again, such injury cannot be diagnosed during routine radiography. PMID- 8209559 TI - The natural history of cervical spondylotic myelopathy. AB - This is a retrospective study of twenty-two patients with cervical spondylotic myelopathy who were admitted to the hospital for surgical treatment of their neurological condition. The purpose of the study was to evaluate the presenting symptoms, factors affecting the diagnosis and the course of the disease prior to surgical intervention. The earliest consistent symptom in all of our patients was a gait abnormality. The course of the disease was one of progressive deterioration. Spontaneous regression did not occur in any of the cases. The vagueness of the initial complaints led to considerable delay in the diagnosis (average of 6.3 years). Magnetic Resonance Imaging (MRI) was the most useful test in confirming the diagnosis. PMID- 8209560 TI - Anterior approach to total hip replacement: surgical technique and clinical results of our first one thousand cases using non-cemented prostheses. AB - Total hip replacement has evolved into one of the most frequently performed reconstructive procedures in orthopaedic surgery today. A modified anterior approach developed by the senior surgeon has been utilized in performing over 3,000 operations in the past two decades. It is a unique and facile exposure. It can be easily applied to primary and revision surgery. Noncemented prostheses have been used in over 1,000 of these operations. This article details the surgical exposure, acetabular and femoral preparation for both non-cemented and cemented prostheses, special considerations for revision surgery, and the clinical results of the experience with noncemented prostheses to date. PMID- 8209561 TI - Cervical spine arthrodesis in rheumatoid arthritis: a long-term follow-up. AB - Forty-one patients with rheumatoid arthritis involving the cervical spine had a posterior cervical arthrodesis. They were followed for a minimum period of seven years. The diagnoses prior to surgery included cranial settling, atlantoaxial subluxation, subaxial subluxation, and any combination of these three. All patients had posterior arthrodesis, with or without methylmethacrylate, and iliac crest autogenous bone graft. In addition, one patient had an anterior vertebrectomy, and two had transoral resection of the odontoid. Follow-up consisted of a subjective questionnaire, standard radiographs, and physical examination, including a neurologic exam. This information was compared to preoperative data available in the patient's medical record, postoperative data, and the information obtained in a similar study undertaken in 1987. At the time of follow-up, thirteen patients were known to be dead. One patient could not be located. Of the remaining twenty-six patients, eighteen underwent the full examination, including physical exam and radiographs. The remaining nine patients were contacted and interviewed, but were unavailable for exam and radiographs. All patients considered the operation a success. Only one patient at follow-up had a non-union. This was stable over time. No patient had a deterioration in neurologic function. There was no significant degeneration or instability seen at levels adjacent to the fused segments as compared to the rest of the cervical spine. Posterior cervical spine arthrodesis for rheumatoid involvement of the neck is a safe, efficacious procedure with no significant deterioration of effects over time. PMID- 8209562 TI - Freeze-dried fibular allograft in anterior spinal surgery: cervical and lumbar applications. AB - Fifty-six patients who underwent anterior fusion utilizing fibular allograft are reviewed. Thirty-two patients underwent multiple-level anterior cervical discectomy and fusion utilizing fibular strut allograft, and 24 underwent anterior lumbar discectomy and fusion using fibular strut allograft. Cervical surgery was performed via the strut technique of Whitecloud and LaRocca and lumbar surgery was performed via a transperitoneal or retroperitoneal approach. Postoperatively, patients were assigned a clinical grade based on symptomatic relief and medication usage. X-rays were visually inspected, and quantitatively digitized for Cobb angle and translation in order to assess the status of arthrodesis. In the cervical group, the rate of clinical success (87.5%) exceeded the arthrodesis rate. By inspection, 65% fused, at a mean time of 23.5 months postoperatively. In the lumbar group, the overall clinical success rate was 68%. This correlated quite strongly with a fusion rate of 58%. Smoking was a negative correlate with arthrodesis. Patients receiving Workers' Compensation were also more likely to have an unsatisfactory clinical outcome. The results of this study highlight the difference between anterior arthrodesis in the cervical and lumbar spine. The biomechanical stability afforded by the fibular strut in the cervical spine appears to outweigh the disadvantages of delayed time to union. The rate of posterior cervical fusion to salvage symptomatic pseudoarthrosis was quite low (9.3%), thus suggesting that additional posterior surgery in this particular group of patients should not be considered for a minimum of two years postoperatively. In the lumbar group, status of arthrodesis correlated closely with clinical outcome. Fusion rate in this group was disappointing, corresponding to other reports in the literature. Based on these data, primary anterior body fusion without allograft in the lumbar spine cannot be recommended, as a viable alternative to conventional autograft. PMID- 8209564 TI - Franklin and Mesmer: an encounter. AB - In 1784, as the Enlightenment was on the wane, Paris faced a debate in which reason confronted the supernatural and the mysterious. Dr. Mesmer, a graduate of the medical school in Vienna, had been running a "magnetic clinic" based on the belief that magnetic fluid, flowing from the stars, permeated all living beings and that every disease was due to an obstruction in the flow. By manipulating that fluid, he launched the concept of animal as opposed to mineral magnetism and claimed to cure all ills. This got him into trouble with the medical faculty, and in 1778 he emigrated to Paris, creating secret societies all over France. Six years later, mesmerism was considered a threat, possibly deleterious to both mind and body. Louis XVI appointed two commissions to investigate this likely fraud. Dr. Guillotin headed one; the other, made up of five members of the Academy of Sciences, included an astronomer and was headed by Franklin, American Ambassador to France. Both commissions concluded that the success of mesmerism was due to the manipulation of the imagination. Mesmer protested vigorously but in vain. He left France and died in obscurity in 1815. PMID- 8209563 TI - The pneumococcus and some men who came to Yale: the Dorothy M. Horstmann Lecture. AB - Yale has been fortunate indeed to have had Dorothy Horstmann as a member of its faculty for all but one of the last 50 years. It has had also the wisdom to take cognizance of her value as an individual and of her contributions to biomedical science and human welfare on two occasions in recent years. Her studies of poliomyelitis, hepatitis, and rubella, executed with perceptiveness, rigor and modesty, have benefited countless numbers; and for her many achievements all are in her debt. I am beholden to her colleagues for this opportunity to pay tribute to a wise and gracious friend. In casting about for a subject befitting this occasion, the thought occurred that it might be of interest to examine the contributions of some former and present members of Yale's faculty to the subject of a group of infections still endemic in all human societies, namely those caused by Streptococcus pneumoniae or the pneumococcus. The list is doubtless not exhaustive but includes such notables as Winternitz, Blake, Paul, Trask, Eaton, and Beeson of former days, as well as reflecting ongoing investigations today by Eugene Shapiro and his colleagues. In reviewing some of this earlier work, it will be my endeavor to place it in the context of contemporary understanding. In the interest of some semblance of order, the material will be examined in topical rather than in chronological order, dealing with bacteriologic and immunologic, pathogenetic, therapeutic, and prophylactic considerations in that sequence. PMID- 8209565 TI - [Initial clinical results with heat-treated homologous bone transplants]. AB - Several ways for HIV inactivation in bone allografts are being discussed. These methods must be efficient, but they must not compromise biologic properties of the allografts. According to animal studies, moderate heat treatment of bone allografts in a 65 degrees C waterbath has no adverse effects on osseointegration. A clinical follow-up study of 49 patients with heat treated bone allografts was conducted. 37 patients with conventional cryopreserved allografts were included in the study as controls. Average follow-up time was 27 months. Results were evaluated by clinical and X-ray examination, using a modified radiologic score. No significant differences in the two groups were detected, except for a slight retardation in bony integration of the heat treated allografts between week 39 and 52 postoperatively. Complication rates were 11.4% vs. 10.7%. In conclusion, moderate heat treatment of bone allografts appears to be a practicable and safe method to improve safety in bone transplantation in clinical practice. In addition to the known guide lines for bone banking heat treating of allografts should be further improved in order to minimize the low remaining risk of infection which exists despite of the three months test. PMID- 8209566 TI - [The stabilizing function of the glenohumeral joint capsule. Current aspects of the biomechanics of instability]. AB - The purpose of the study was to determine the influence of rotation torques on superior-inferior and anterior-posterior translation in various degrees of abduction in the glenohumeral joint. 16 cadaveric shoulders were tested using a specifically designed four-degrees-of-freedom mounting apparatus and a 6-degrees of-freedom tracking system which allowed of dynamic and static measurements by means of ultrasound (Zebris) Internal/external rotation torques and translation forces in the inferior-superior and anterior-posterior plane were applied in 0 degrees, 45 degrees, 75 degrees and 85 degrees of abduction. Shoulders were tested intact, vented, after severing of the acromion and coracoid (7 shoulders) and after subsequent division of the anterior capsule at the glenoid margin including a T-shaped incision (8 shoulders). Venting of the capsule resulted in a significant increase in ap-translation only in abduction of less than 45 degrees. Rotation torques and an abduction of more than 45 degrees effected a centering of the humeral head against translation-forces in the anterior-posterior and superior-inferior direction. The weakening of the anterior capsule by a T-shaped incision, in which circular fibers were also severed, significantly increased the anterior translation in comparison to that obtained after an incision along the glenoid margin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209567 TI - [The risk of neurovascular damage in elbow joint arthroscopy. Which approach is better: anteromedial or anterolateral?]. AB - In a cadaver dissection study the relation of the arthroscopic portals to the neurovascular structures was documented. In six cadaveric elbows the capsule was distended with 35-40cc fluid of 0.9% NaCl by using the direct lateral portal. An anterolateral and anteromedial approach to the elbow joint were established. The distance of the arthroscopic portals to the neurovascular bundles were measured at empty and filled joint after performing an anatomic dissection. The influence of flexion and extension of the joint as well as pronation and supination of the forearm on the distance of the arthroscopic sheath to the neural structures was documented. Lesions of the superficial cutaneous nerves were not seen. Using the anterolateral portal in the best position of the joint (90 degrees flexion and not distended joint at max. pronation of the forearm) we measured a proximity of 4.5 mm (range 2-10 mm) to the radial nerve. For the anteromedial approach the mean distance of the median nerve to the arthroscopic sheath was 15.5 mm (range 8 27 mm), when the optimal joint position was used (90 degrees flexed joint, distended, max. supination of the forearm). PMID- 8209568 TI - [Results of histological studies of the flexor tendon sheath in 35 flexor tenosynovectomies in carpal tunnel syndrome]. AB - This paper presents the results of histologic studies conducted in the context of tenosynovectomy of the flexor tendons to treat carpal tunnel syndrome. The most common findings were inflammatory changes of the synovial sheath, vascular pathology and fibrous changes of the connective tissue. PMID- 8209569 TI - [Spontaneous osteonecrosis of the iliac crest. Description of a formerly unverified location]. AB - In a 27-years old male a radiographically well defined and compact area with some lucent sections was found incidentally at the top of the left iliac crest. The resection and the following histomorphologic examination of this tissue brought the diagnosis: spontaneous osteonecrosis of the iliac crest. To our knowledge this is the first time that the iliac crest has been proved as a localisation of the spontaneous osteonecrosis by histomorphologic examination. PMID- 8209570 TI - [Femoral head dysplasia and its relationship to femoral head necrosis (Perthes' disease)]. AB - Fifty-five patients totaling 98 hips afflicted by Dysplasia Capitis Femoris (DFC), monitored between 1960 and 1983, were analyzed. Mean follow-up: 8 years and 4 months (minimum 2 years, maximum 22 years and 2 months). Forty-three (78%) patients were males; fourteen (25%) were females. Non displayed any alteration in other osteoarticular segments. In 24 of the 98 affected hips it was possible to determine the exact radiological age appearance of the Epiphyseal Nucleus. Thirty seven of the 55 patients had moderate signs and symptoms which were of short evolution. According to presence or absence of necrotic signs of the femoral epiphysis, two types of lesions were classified: Type 1: Pure Dysplasia Capitis Femoris (88 hips). Type 2: Dysplasia Capitis Femoris with unequivocal signs of necrosis (10 hips). Upon review of the 98 diseased hips, 80 (81.63%) had been fully repaired, while 18 (18.37%) were in reparatory stage. From the 80 fully healed hips, 56 were normal; 18 exhibited a Spherical Coxa Magna and 6 had a non spherical epiphysis. As treatment concerns, patients with D.C.F. Type 1-A or Type 1-B only require observation and periodical control in addition to moderate restrictions in physical activities upon presence of symptomatic pain that is transitional. Patients with D.C.F. Type 2 must be treated as a classic case of Perthes Disease. Finally, a hypothesis of their etiopathogenis and its relationship to Perthes Disease is brought forth. PMID- 8209571 TI - [Indication for Chiari's pelvic osteotomy]. AB - The results of 61 Chiari's pelvic osteotomies carried out during a 10 years period are reported. Present role of the operation in the correction of acetabular dysplasia in comparison to Pemberton's acetabuloplasty, to triple pelvic osteotomies and to the prosthetic replacement of the hip joint is discussed. In conclusion the operation is still indicated in special cases. Depending on the age of the patients pain can be observed already after 3-5 years however a great part of the patients is completely free of complaints even 10 years postoperatively. PMID- 8209572 TI - [5-year experience with De Bastiani's method of extremity lengthening]. AB - From 1987-1991 19 patients had 20 lengthenings in 23 bones. The average hospitalisation time was 54 days. The time to lengthen one limb was 30 weeks on an average. In a retrospective study the cases were analysed according to Paley's criteria. Our complication rate is compared to that of other authors. We have to cope with a rather high rate of complications. 17 out of 19 patients showed good or very good final results. PMID- 8209573 TI - [Visual evaluation of conventional roentgen pictures and dual x-ray absorptiometry in the diagnosis of osteopenia]. AB - Routine radiographs and PA dual x-ray absorptiometry (DXA) of the lumbar spine were performed in 253 patients. A T-score of -2SD (approximately 20% reduction from young normal bone mineral density (BMD)) as measured by DXA, was used as threshold for the diagnosis of osteopenia. A lumbar spine index (LSI) as proposed by Barnett and Nordin was assessed by one radiologist. The correlation between LSI and bone mineral density, measured by DXA, was poor, and our results indicate that osteopenic patients cannot be differentiated from non-osteopenic patients by LSI. 100 radiographs of the lumbar spine were evaluated by 9 observers in order to determine observer variation in the detection of osteopenia. A complete agreement between the readers for the diagnosis of osteopenia was achieved in 43 percent of all radiographs. DXA and observers agreed in 68 to 76 percent of all cases. For a decrease of BMD of more than 60 percent compared to young normal adults, as determined by DXA, all readers agreed in the diagnosis of osteopenia, whereas for higher BMD values the agreement between readers and DXA worsened. The inconsistency between DXA and observer agreement was greatest for patients with a BMD reduction between 10 and 20 percent. The mean values of the kappa coefficients were 0.574 +/- 0.06 for interobserver variation and 0.437 +/- 0.06 for the agreement between readers and DXA-results. An only moderate kappa coefficient of 0.573 for the intraobserver variation as determined in one reader was found. PMID- 8209574 TI - [Extra-abdominal aggressive fibromatosis: case report and literature review]. AB - The extra-abdominal aggressive fibromatosis is a locally aggressive non metastasizing fibroproliferative tumor of the locomotive system with an extremely high recurrence rate. By means of a case report the treatment possibilities are discussed. The recommended treatment of choice is a wide resection where possible. The indications for radio-, chemo- or hormone therapy are presented. PMID- 8209575 TI - [Knowledge of the human body. At the 450th anniversary of the first edition of Andreas Vesalius' life work. "De Humani Coporis Fabrica Libri Septem"]. AB - As an introduction to the symposium we pay attention successively: firstly, to the "Magister divinus", to Andreas Vesalius' personality, according to the testimony of his pupil Fallopius; secondly, to his ingenious lifework, the "De Humani Corporis Fabrica", according to the opinion of Sir William Osler, "the greatest medical book ever written", finally, to the historical evolution leading to the Vesalian way of thinking and working. All this proves that Vesalius' work is a fundamental turning point in the development of medicine as well as in the evolution of scientific practice in a general sense. It is also one of the highlights in the construction of mankind's intellectual patrimony. PMID- 8209576 TI - [Vesalius or the fascinating encounter of art and anatomy]. AB - The De Humani Corporis Fabrica is an essential moment in the history of western civilization. Being a headline of the Renaissance, it is far more than an anatomical textbook and an artistic masterpiece, that will stay unrivalled for a long time. The Fabrica indeed gives us a new vision of Man and of the World, bound together with an unprecedented rise of science and technology, providing Europe with the opportunity to outpace decisively the parallel civilizations. In this respect, we analyse the Fabrica both in its scientific and its artistic aspect; we show that if Vesalius takes part in the anatomical revolution in his time, it is too schematic to call him "the father of modern anatomy" while other anatomists of his time also took part in that revolution. On the other hand, the radically enforced a new view of the human body that will stamp anatomical knowledge and its practice for several centuries. PMID- 8209577 TI - [Andreas Vesalius and surgery]. AB - By publishing De Humani Corporis Fabrica Libri Septem in 1543, Andries van Wesel (1514-1564) gave surgical science an immense impulse. The revolutionary renovation in the knowledge of man's anatomical structure changed slowly and progressively into topographical and physiological understanding of surgical diseases. At the same time, this made better aimed and more secure operations possible. Apart from the importance of this anatomical publication, Andreas Vesalius also won his spurs as a surgeon. He taught surgery in Padua for many years. He was appointed court physician and surgeon at the Habsburg Court of Charles V and Philip II. He personally performed lots of operations known at the time as major ones. He not only quickly adopted the surgical innovations of his fellow-surgeon Ambroise Pare, but he even performed operations that had been forgotten during several centuries, among which thoracocentesis for pleural empyema. His clinical perspicacity in discovering the indication for some operations was staggering and was appreciated by all great monarchs of Europe in the 16th century. In his several consilia, numerous pieces of advice were given for the treatment of surgical patients. The surgical practice which Vesalius had in Brussels for many years, consequently became most successful. Many publications by Vesalius about surgery and blood-letting are well-known. His Chirurgia magna in septem Libros digesta still remains controversial; these books were published by Prospero Borgarruccio (1560) in 1568 by the Venetian editor Valgrisi. This book gives an excellent survey of surgical pathology as it was taught and treated in the 16th century. The scientific method that Vesalius used, not only in his anatomical studies but also in his surgical practice, deserves not only our full appraisal but should still be studied in our own time. PMID- 8209578 TI - [Vesalius and the nervous system]. AB - Before we comment the subject of this lecture, we attract the reader's attention towards two remarks. We first want to point out that, although Vesalius is rightly considered as "the father of anatomy", in physiological matters--such as e.g. the physiology of the nervous system--he remained a faithful follower of Galen. A second preliminary remark explains why the books Vesalius devoted to the nervous system, namely the fourth and seventh books, as well as a part of the third book, don't belong to the best parts of the Fabrica, when we compare them with his Osteology and his Myology. We should not forget that some technical discoveries such as keeping brain-tissue in alcohol in order to harden it and colouring methods of Weigert, Marchi and Nissl, that made a refined macro- and microscopic examination of the nervous system possible, were only invented in the 19th century. The fourth book considers the peripheral nervous system. According to Vesalius, there are seven pairs of brain-nerves. His first pair corresponds to our Nervous opticus; his second pair concerns our Nervi oculomotorius, trochlearis and abducens; this third pair embraces a great part of our Nervus trigeminus; his fourth pair corresponds to our Nervus maxillaris; his fifth pair includes our Nervi facialis and acusticus; his sixth pair includes our Nervi vagus and accessorius; his seventh pair our Nervi hypoglossus and pharyngeus. Vesalius counts thirty pairs of spinal nerves. His description of the Plexus brachialis and the Plexus ischiadicus is closely related to the modern views in these matters. However, his teleologic views about them are remarkable, e.g. about the course of the Nervi recurrentes. The seventh book covers the brain. He successively and truly describes the cerebral membranes, the Ventriculi, the Cerebrum; his description relies on a series of horizontal slices. He also describes the brain-stem and the Cerebellum. Vesalius, who had doubts about the existence of the Plexus reticularis in Man, gives a tendentious description of the Infundibulum based on a false physiological theory about the secretion of "pituita", which he considers as the sluggish refuse of the ventricular system. A chapter of the third book is devoted to the blood circulation in the nervous system, with the unavoidable errors derived from Vesalius' galenic theories about blood distribution. We should point out the fact that Vesalius emphasizes quite rightly the metameric blood circulation of the spine. Finally, we should also emphasize the beauty of the images concerning the nervous system in Vesalius' works. PMID- 8209579 TI - [Vesalius' Fabrica and the anatomy of the masticatory system]. AB - In this Tabulae sex, Vesalius does not dare contradict Galenus views too definitely: in the upper jaw he counts fifteen bones amongst which the Os intermaxillare, and two bones in the Mandibula. In the Fabrica, he maintains the unity of the Mandibula; he denies the presence in man of the Os intermaxillare and counts in the upper jaw twelve bones (amongst which the Os planum). He denies the existence of the Vomer and the lower nose-shells. He gives a lyrical description of the Sinus maxillaris, but without an evident image. The under-jaw is moved by four pairs of muscles, which he does not name but numbers. The Musculus pterygoideus lateralis is not described. Jaws, tongue and teeth are tended, not by the Nervus trigeminus, but by the third and fourth pairs of the seven "brain nerves". The thirty-two teeth are divided into "cutting-teeth", "eye teeth" and "molars", but, with their roots they are pictured in a wrong occlusion. Vesalius declares more than once, that he discovered the pulp-chamber and also the chamber of the smaller bones and concludes hereby that teeth have got all the characters of bones. They consequently are made of only one substance. Their chamber lies as far of the chewing-surface as of the summit of the root and is filled with a kind of marrow. Blood-vessels and nerves penetrate into the side of the hard substance of the hidden part. Vesalius does not make any difference between milk teeth and the permanent dentition. Just like a long bone, a tooth possesses a diaphysis and an epiphysis, for which he uses the word "appendix". In both cases the two parts only join at the end of the growth. When about seven years, the "appendices" fall out, they are replaced by their "diaphyses". If this does not happen, for instance in the big molars, diaphysis and appendix grow firmly together. Vesalius' therapy for early caries is surprising. If, in a child a permanent tooth gets injured, and if only the crown is removed, the tooth is replaced by a "new" tooth. PMID- 8209580 TI - [Vesalius and the anatomy of the female genital tract]. AB - Some of Vesalius' books allow us to clarify his knowledge of the anatomy of the female genital tract. We distinguish chronologically his Tabulae anatomicae sex (1538), the Fabrica (1543), the Letter on Chynaroot (1546), the Fabrica II (1555) and his letter to Falloppio (1564). The whole of these writings gives us an overview of the evolution of the insight concerning this important chapter of human anatomy. Anno 1538, Vesalius is in several matters Galen's pupil. Let us consider his pictures of the tractus genitalis of man and woman, which unmistakably follow the galenic theory of sexual isomorphism, a delusion to which our Brussels anatomist adhered during all his life. On other points he outdid the "Master" from the very beginning, e.g. as to the structure of the uterus. In this matter he followed da Carpi (1470-1550), his immediate predecessor and the man who pictured a woman's womb as "Uterus simplex". But even in this matter, Vesalius could not separate himself completely from the antique scheme: near the fundus uteri he draws two "ears" or cornua wherein he lets the oviducts discharge themselves, mythical structures that will disappear from his pictures, from 1543 on. The epididymis-like structure of the oviducts will nevertheless be maintained. The chapters 15 to 17 of the fifth book of the Fabrica stand centrally because herein it is the first time that these parts are systematically and thoroughly described; moreover, the pictoral aspect means a great renovation. Before Vesalius, no anatomist had ever published such detailed and artistic pictures of the female organs. But knowing that text and illustration were made at the dissection table, we should consider the author's mistakes as more conspicuous. Thus for instance, the oviduct as vas semen efferens, the structure of which he "saw" in line with Galen's propagation theory. For Vesalius the uterine tube has remained the homologue of the complex canals through which the male seed leaves the body. Another example of an erroneous "observation", inspired by the functional theories of his predecessors, is the imagined connection of blood-vessels between the female internal organs and the breasts. The needlessly complicated terminology and Vesalius' describing and paraphrasing anatomical nomenclature are not very favourable to an easy reading of this works. His classification of the parts of the genital tract is confusing, the more as it is not consistent. We already said that Vesalius attributes but one cavity to woman's uterus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8209581 TI - ['A sad and painful heart'--Andreas Vesalius as cardiologist]. AB - One needs courage to dissociate oneself from ideas maintained for ages and put forward by authorities. How laborious this process has been for Vesalius concerning the heart, is obvious when we compare the information of an eye witness with both editions of the De Humani Corporis Fabrica (1543 and 1555). He must have come hesitantly to the conclusion that the views on the permeability of the septum cordis, as they were supported by Galen, Mondino and Johann Winther, a professor at Louvain, could not be defended. However, they had been essential in the considerations about the blood-flow. Although Vesalius demonstrated by vivisection-experiments that a relation exists between the pulse and the heart contractions, he was not an experimenting cardiophysiologist. In this respect, he stood far behind his contemporary Leonardo da Vinci, who made experiments on heart ntractions and the bloodstream along the heart valves. Vesalius was an anatomist! And a morphologist! But he was also a physician. In this respect, he also was interested in the pathological aspects of anatomy. So he recalled in, his last book, Anatomicarum Gabrielis Fallopii Observationum Examen (1564) some cardiologically interesting patients, a.o. the courtier van Immerseel, with a very unequal pulse and "a sad and painful heart" (tristi in corde, sensu doloreve), by whom a heart abnormality was found post mortem, that in modern terms we could call "an old heart infarction with thrombus formation." According to Schenk von Grafenberg, Vesalius was dreaming of a big book about anatomo pathology, but alas, he never wrote it. Undoubtedly he would have trusted more his eyes and less Galen: "non solum ex Galenis testimonio, sed etiam oculis ipsis perspexeris". PMID- 8209582 TI - The educational responsibilities of a National Academy of Medicine. AB - Academies of Medicine now should see their educational mission as concern with all stages of medical education in the nation. Traditionally, National Academies have tended to regard Postgraduate Training as their proper educational responsibility. Such limitation is no longer defensible, particularly because medical education is now accepted as a continuum and, moreover, is viewed as lifelong. Discontinuities between basic education, specialist training and continuing education are now considered detrimental, and have to be eliminated. The Medical School Curriculum must be required to equip future doctors with the self-learning skills now essential for specialist training. The longest and most critically important phase of training has unquestionably become continuing medical education. It is argued therefore that basic medical education, specialist training and continuing education have all to be concerns of National Academies. National Academies in Europe, inevitably, have come to have profound international obligations now that free movement of doctors is legally established in the European Community. PMID- 8209583 TI - [Observations on current surgical viewpoints in gynecological and breast oncology]. AB - Radical surgery in gynaecological and mammary cancerology exists one century. Better results as longer survival and disease free intervals are the consequences of the progress of scientific and technical advancement. The five-year survival for the total group (stages I to IV) of malignant tumours in a personal series is 65% and the ten-year survival 53%. A general discussion about all the problems of this part of cancerology and the bibliography can be found in the recently published books. PMID- 8209584 TI - [Do hormones determine our fate?]. AB - The hormonal system is a communication system between cells and organs. Hence it is not surprising that it influences almost all physiological functions and, at least partially, our behaviour and fate. The sexual phenotype is determined by the sex hormones. Normally, the phenotype is in accordance with gonadal and genetic sex, but occasionally, as a consequence of enzymatic defects in the biosynthesis of sex hormones or of androgen resistance, gonadal and genetic sex are in discordance with the phenotype, the latter determining generally the civil sex and the sex of rearing. Whereas the gender role is generally determined by the sex of rearing and the phenotype, itself under hormonal influence, homo- and transsexuality constitute notorious exceptions to this rule. Although several authors consider homo- and transsexuality to be the consequence of an impairment in androgenic impregnation in the perinatal period, there are at present no convincing arguments for an hormonal origin for either homo- or transsexuality, although such a possibility can't be excluded either. Besides their role in psychosexual behaviour, sex hormones play also a role in our life expectancy. Indeed, although maximal life expectancy of man is genetically determined, a major determinant of individual life expectancy is cardiovascular pathology. The latter is partly responsible for the difference in life expectancy between men and women, cardiovascular mortality increasing rapidly at menopause and being halved by oestrogen replacement therapy. Also atherogenesis as such is, to a large extend, under hormonal control. Indeed insulin resistance and hyperinsulinism, which develop as a corollary of the aging process, is an important cause of atherosclerosis as well as of hypertension. Other hormones also play an important role in our behaviour. We can mention here the role of the thyroid hormones in the physical and mental development of children as well as in the regression of the intellectual functions in hypothyroidism; the role of growth (and sex) hormones in the clinical symptomatology of aging; the memory enhancing effects of the antidiuretic hormone; the role of growth factors (as well as of sex hormones) in tumorigenesis; the role of corticoids (and sex hormones) in the modulation of immunological processes etc. In brief, hormones influence all aspects of our life. PMID- 8209585 TI - [The choice of the surgical procedure in a multiple occlusive lesion of the arteries supplying blood to the brain]. AB - Over 50% of ischemic lesions of the brain are caused by great artery occlusions mainly due to atherosclerosis, various arterial deformities, as well as to extravasal compressions. Almost half the patients have a concomitant two- or more artery lesions. There are many reports on the surgical treatment of multiple occlusive lesions of extracranial arteries, but the choice of surgical policy is little studied. The author's study has shown that the surgical policy largely depends on the reserves of collateral cerebral circulation and hemodynamic parameters of all arteries. In revascularization requiring a temporary arrest of blood flow along one of the great cerebral arteries, priority should be given to correction of a less hemodynamically significant artery. In patients with multiple occlusive lesions of the great arteries, preference should be given to surgeries not requiring temporary artery occlusion. For adequate cerebral circulation maintenance, it is necessary to surgically correct as many arteries as required. If required, corrections of several arteries should be made at several stages at an interval of 1.5-2 months. PMID- 8209586 TI - [Clinico-neuropsychological studies of patients with arteriovenous malformations who have had hemorrhages with blood in the cerebral ventricles]. AB - The clinical and neuropsychological signs were studied in 32 patients with arteriovenous malformations of various site who had sustained hemorrhages into the cerebral ventricles. The studies allowed the authors to identify the neuropsychological syndrome which involved the following signs: disorientation, chiefly in time, marked inertia in various scopes of activities, emotional and volitional disorders, and dysmnesia. Memory defects were seen in all spheres of mnestic activity: there were abnormalities in the actualization of consolidated knowledge, modal non-specific memory disorders in the experiment, defects in memory for current events. The degree of defect severity was found to be directly proportional to that of prior hemorrhages. In the absence of hydrocephalus, the disorders were regressive. The authors discuss what topical belonging of the detected syndrome is and how it is related to the phase of consciousness restoration. PMID- 8209587 TI - [The combined treatment of patients with primary gliomas of the lateral ventricles and the septum pellucidum]. AB - The authors' material was based on the analysis of 49 patients with primary gliomas of the lateral ventricles and transparent septum who were treated from 1988 to 1992. The main method of patients' selection was to analyze clinical and topographic data obtained from computed and magnetic resonance tomographic studies. In 39 (79.6%) cases, the tumors were found in the cavity of the lateral ventricles, in 10 (20.4%) cases there was a partial paraventricular growth when the bulk of the tumors was located in the lumen of the lateral ventricles. Out of the 49 patients examined, 46 (93.3%) were operated on, while 3 (6.1%) patients were found inoperable. In 37 (80.4%) cases, an external ventricular drain was set at the end of an operation. The operative material was histologically studied in 46 cases. Following the operation, 24 (52.2%) patients underwent split fractional radiation therapy with a total focal dose of 60 Gy. The postoperative mortality was 15.2%. The follow-up of patients was from 1 to 4 years. The combined treatment of patients substantially prolonged the relapseless period of the disease. At the same time, the postoperative longevity of patients with malignant gliomas of the lateral ventricles and transparent septum becomes similar to that of the relapseless period in patients with low-grade gliomas untreated with radiation rays. PMID- 8209588 TI - [The ophthalmological symptoms of chiasmatic gliomas in children in the pre- and postoperative periods]. AB - The paper outlines the ophthalmological symptomatology in 61 children aged 2.5 to 15 years who had great and giant chiasmal gliomas. The ophthalmological symptomatology among the first clinical manifestations was found in 86.9% of cases and remained prevalent throughout the follow-up. There was a correlation between the status of visual functions and the site of a tumor. The tumor affected mainly the chiasma in 6.6% of cases, the chiasma and the both optic nerves in 26.2%, the chiasma and an optic nerve in 62.2%. The ophthalmological and neurological symptomatologies are of value in choosing a surgical treatment. A subtotal and partial removal of the tumor was performed in 51 and 10 patients, respectively. Its removal resulted in an improvement and stabilization of visual functions in 14.3 and 41.1% of cases, respectively. Thirty-three patients were followed up for 4 months to 8 years. Visual improvement occurred in 36.4% in the late period. There was a relapse in 9.1% of cases. PMID- 8209589 TI - [The effect of dimephosphon on the cerebral circulatory regulation system in patients with brain tumors]. AB - The paper provides the results of studies of the effects produced by the new vasoactive agent Dimephosphone, which normalizes the function of the nervous system, on the performance of the regulatory mechanisms responsible for the circulatory provision of chemical and physical homeostasis of the brain in patients with cerebral neoplasms. A five-day course of Dimephosphone monotherapy was demonstrated to normalize the cerebral circulatory regulatory system in the preoperative period. Preoperative Dimephosphone normalization of the regulatory mechanisms of cerebral circulatory provision ensures the tolerance of the cerebral circulatory system to intraoperative injury. The drug used in the course treatment of patients accelerates the normalization of cerebral vascular responsiveness at the site of surgical intervention. PMID- 8209590 TI - [Microsurgical revascularization of the brain with an autograft of the greater omentum (experimental research)]. AB - The paper deals with improvement of procedures for autografting a greater omental fragment to the vascular layer of the brain in its experimental ischemic lesions. The findings suggest that a functional vasculature has formed between the omentum and the meninx vasculosa just at hour 24 postautografting. This provides evidence to recommend the method for clinical application to compensate cerebral circulatory disorders in tumor-induced and vascular abnormalities in the brain. PMID- 8209591 TI - [Changes in the cerebral hemodynamics during Rohypnol anesthesia in neurosurgical patients]. AB - Intracranial pressure, cerebral perfusion pressure, and intracerebral blood volume changes were observed in 43 patients with volumetric intracranial processes (intracranial hematomas, tumors) during general rohypnol anesthesia. Intracranial and cerebral perfusion pressures were found to correlate with intracerebral blood volume. Rohypnol anesthesia decreased intracranial pressure by 25% due to reduced arterial blood influx into the head, mechanisms responsible for autoregulation of cerebral circulation being intact. PMID- 8209592 TI - [The microsurgical treatment of arterial aneurysms of the ophthalmic segment of the internal carotid artery]. AB - The authors summarize the experience gained in microsurgical treatment of ophthalmic segment aneurysms in the internal carotid artery at the N. N. Burdenko Institute of Neurosurgery during the past 10 years. The paper analyzes clinical data on 110 patients with arterial aneurysms of the ophthalmic segment of the internal carotid artery, of whom 50 have undergone microsurgery. A classification of ophthalmic segment aneurysms in the internal carotid artery and a differential choice of a surgical access to them are given in the paper. PMID- 8209593 TI - [A method for the stereotaxic aspiration of intracranial hematomas by using the data from ultrasonic scanning]. PMID- 8209594 TI - [A device for the monitoring control of retraction pressure during neurosurgical operations on the brain]. PMID- 8209595 TI - [The new nonionic contrast preparation for myelography iotrolan]. PMID- 8209596 TI - [Subdural hematomas in indirect head trauma]. PMID- 8209597 TI - [The diagnosis of multiple aneurysms in the acute period of subarachnoid hemorrhage]. AB - Among arterial aneurysms of the brain, multiple aneurysms occur on the average in 12.9% patients as evidenced by angiographic studies and in 22.7 as shown by autopsies. The study was undertaken to examine 66 patients with multiple aneurysms who had undergone surgical treatment. Their mean age was 45 years. The examination has demonstrated that total cerebral angiography should be performed to diagnose multiple aneurysms. The comprehensive studies of the patients that involved neurological examinations, computed tomography of the brain and total cerebral angiography have enabled the ruptured aneurysms to be detected in 68% of cases and in 85% when aneurysms are located in various vascular beds. While defining the surgical policy for patients with multiple aneurysms in the acute hemorrhagic period, it is necessary to bear in mind that there can be repeated hemorrhages from the previously unbled aneurysms. PMID- 8209598 TI - Results of the SAnGUIS study in Belgium. A concerted action of the Commission of the European Communities IVth Medical and Health Research Programme. The Belgium SAnGUIS Study Group. Safe AND Good Use of blood In Surgery. PMID- 8209599 TI - [Rehabilitation after anterior cruciate ligament suturing]. AB - The authors discuss problems of rehabilitation after suture of the anterior cruciate ligament where frequently errors are committed and where inadequate rehabilitation may cause damage to the patient. Different periods of rehabilitation after LCA sutures are discussed and suitable methods of exercise for different periods are recommended. PMID- 8209600 TI - Current state of cementless hip prostheses. AB - Cemented cups in the young patient continue to show an unacceptable rate of early aseptic loosening. A well designed cementless prosthesis, implanted with good technique, is a better alternative. With the uncertainty surrounding the femoral stem, a hybrid total hip with a cemented stem and porous ingrowth cup remains an acceptable interim solution. There is an ongoing problem with the wear debris produced by the available implant materials. There is hope that the newer materials will help in this regard. Custom made prostheses at this time, seem most suited for those hips with marked deformity making the use of standard systems difficult. The use of cement in the elderly population remains an acceptable technique with the advantages of immediate fixation and early weight bearing. PMID- 8209601 TI - [Transpedicular stabilization in fractures of the thoracolumbar spine. II]. AB - Proceeding from the literature survey and on the basis of his own experience the author presents a current concept review of the problems of the transpedicular stabilization in fractures of the thoracolumbar spine. Individual chapters are devoted to the biomechanics and transpedicular screw placement, classification of implants and to the transpedicular operations on the injured vertebral body. Based on both his own experience and survey of the literature the author recommends the following: in order to increase the stability of osteosynthesis to place transpedicular screw in anteromedial direction (Magerl approach) close to the anterior cortex of the vertebral body or (in case of osteoporosis) to perforate it by tip of the screw. in fractures with the compression of vertebral body (mainly in case of burst fractures) to perform transpedicular reduction and cancellous bone grafting after Daniaux and Dick. Out of the implants so far used the author considers the best Fixateur interne (Dick) allowing facultless reduction as well as a longterm stabilization of the fracture. PMID- 8209602 TI - [Problems with international and Czech anatomic nomenclature]. PMID- 8209603 TI - [Arthroplasty of the elbow joint]. AB - The authors present a review on the development of arthroplasties of the elbow. Modern arthroplasties are divided into basic groups and their main advantages and disadvantages are characterized. The authors describe in detail the construction and technique of Souter-Strathclyde total endoprostheses of the elbow based on the authors' own experience. Total endoprostheses of the elbow are the only solution which can ensure at the same time marked relief from pain, a satisfactory range of movement and stability of the operated joint. PMID- 8209604 TI - [Using of a Wagner stem in revision-arthroplasty following loosening of a total hip endoprosthesis]. AB - During a three-year period to 50 patients a Wagner femoral revision endoprosthesis was implanted. The mean age of the patients was 67.5 years. In 39 patients replacement of an endoprosthesis was involved, in 7 patients the indication was fracture in the area of the endoprosthesis, 4 patients were operated for other reasons. Of 44 patients, who were operated at least 12 months ago, 33 were checked. Sixteen patients were classified according to Harris' score as very good, 9 as good and in 4 the result was satisfactory or poor. Wagner's revision shank is suitable in particular in damage of the proximal femur, where in case of firm distal anchoring and early ability to burden the extremity proximally, marked new formation of bone was observed with restoration of the pipe-shaped bone structure. PMID- 8209605 TI - [Long-term results of implantation of polyethylene screw sockets using Edler's method]. AB - High-molecular polyethylene is used in many technical spheres and in orthopaedics it is used in particular as a sliding component. In orthopaedic endoprosthetics it serves as a material for the manufacture of sockets, whereby polyethylene sockets can be anchored with our without cement. Morphological research corroborates the suspicion of inadequate static firmness of the polyethylene used and this may lead to abrasion and thus mechanical loosening of Endler's screw socket and subsequently also of the metal shank. At the orthopaedic department of the General hospital in Zwettel (Austria) between 1984 and 1987 113 Endler sockets were implanted in 101 patients. So far 41 reoperations were made in 39 patients. In 71% of the patients replacement by a non-cemented socket according to Zweymuller followed, in 17% by a cemented socket according to Muller. In 4 joints at the same time also the femoral component had to be replaced, in 13 shanks bone rarefaction in the area of the calcar femoris was detected. In shanks with removable heads the head was always replaced. Clinical evaluation of the operated patients was done according to the procedure of Merle d'Aubigne. PMID- 8209606 TI - [Retrospective study of heterotopic ossification with and without prophylactic indomethacin therapy]. AB - The authors evaluate the problem of heterotopic ossifications as a complication of total endoprostheses of the hip joint. The classification into stages as elaborated by Arcque was used and compared with the clinical correlate. The authors compared the year 1989 when the total number of prostheses was 150 without prophylaxis of ossifications, with the year 1992 when the total number of endoprostheses was 200 with prophylaxis. In 94% of the patients starting on the second day after surgery to the 21st postoperative day 2 x 50 mg Indomethacin (2 x 1 capsule Indocin forte) were administered. As a gastroprotective drug the patients were given Ranitidine, 2 x 150 mg (2 x film tablets Zantac 150). Complications such as gastrointestinal complaints and skin exanthemas were observed only in 6 patients. Prophylaxis of thromboembolic disease was used in 1992 in 65% of the patients by anticoagulants and in 35% of the patients by administration of low-molecular heparin. This procedure proved a very simple, effective and safe method for prevention of para-articular ossifications: [table: see text] PMID- 8209607 TI - Custom made total knee-replacement in patients with primary and secondary bone tumors. AB - The authors present an account of a group of 51 patients to whom an individual endoprosthesis of the knee joint was implanted on account of a tumour. A primary bone tumour was involved in 42 cases and a metastatic process in 9 cases. Twenty four endoprostheses were cemented, 26 were implanted without cement. The mean follow-up period was 43 months. Functional results excellent and good in 61%, poor results only in 5%. PMID- 8209608 TI - [The Kessel-Gschwend approach to the shoulder joint]. AB - The solution of pathological conditions in the subacromial space is essentially not only a diagnostic problem but also a problem of the surgical approach. Exposure of the necessary space is practically always associated with slackening of the muscles; usually the deltoid muscle is affected which leads to hypotrophy, frequently to muscular atrophy with an adverse impact on the function of the shoulder joint. Gschwend's modification of Kessel's approach reduces muscular hypotrophy and the risk of damage to a minimum and permits to treat the described affections of the shoulder joint, with rapid restoration of normal function of the joint. The approach was used for the surgical treatment of injuries of the rotator cuff, impingement syndrome and other diseases with favourable results. PMID- 8209609 TI - [Bone marrow fibrosis in neoplastic diseases of the hematopoietic system]. AB - Bone marrow fibrosis appears with diverse extension in most neoplastic diseases of blood. It may cause difficulties in establishing a firm diagnosis. In some cases bone marrow fibrosis has a prognostic value. PMID- 8209610 TI - [Biological properties and clinical applications of interferon gamma (IFN gamma)]. AB - Interferon-gamma (IFN-gamma) is produced by activated T cells and probably by NK cells. Its production can be induced by mitogens, antigens and other molecules. IFN-gamma interacts with cells by binding to specific membrane receptors. IFN gamma--1b is an Escherichia coli--derived recombinant DNA product, which has biological activity identical to natural human IFN-gamma. This IFN type is a more potent immunomodulator than IFN-alpha and IFN-beta. Long term treatment with a therapeutic dosage of IFN-gamma--1b produces a significant reduction in the incidence of serious infections in patients with chronic granulomatous disease. This cytokine can be also useful in the treatment of patients with visceral leishmaniasis, Epstein-Barr virus infections, lepromatous leprosy and other infectious diseases. Phase I and II studies have demonstrated it to be capable of producing antitumor effects, especially in metastatic renal cell carcinoma and some hematologic malignancies. Clinical trials have suggested efficacy of IFN gamma in the treatment of severe atopic dermatitis and rheumatoid arthritis. The most common adverse reactions are fever, headaches and erythema at the injection site. PMID- 8209611 TI - [Splenectomy in adult patients with idiopathic thrombocytopenic purpura after intravenous immunoglobulin treatment]. AB - Eight patients with idiopathic thrombocytopenic purpura (ITP) and no response to steroids therapy were prepared for splenectomy, for 5 consecutive days, with intravenous immunoglobulin (IVIG, 0.4 g/kg body weight). Increase of platelet counts and/or remission of haemorrhagic diathesis were observed in 7 patients, in one case IVIG proved ineffective. Splenectomy was performed in 7 cases and the postoperative course was uneventful. IVIG treatment has proved efficient in preparing ITP patients for splenectomy. PMID- 8209612 TI - [Preliminary evaluation of adverse effects after administration of arabinoside cytosine (Ara-C) in high doses to children with acute myelogenous leukemia]. AB - Five children with AML were treated with high-doses of Ara-C (2 g/m2) during consolidation. After 17 cycles the toxicity was evaluated. Granulocytopenia (< 0.5 x 10(9)/l) and thrombocytopenia (< 25 x 10(9)/l) were stated after 15/17 and 13/17 cycles respectively. The nadir of bone marrow suppression appeared between day 10 and 14. In one case treatment related death during severe myelosuppression was noted. In individual cases jaundice with elevated activity of aminotransferases, paralytic ileus and pulmonary oedema were observed. All these adverse reactions were reversible. Other toxicities such as nausea/vomiting, stomatitis, diarrhea, infections and drug related fever were transient. No neurologic toxicity was seen. There is a need for developing a new way of the administration of high-dose Ara-C which could substantially reduce toxicity of the drug. PMID- 8209613 TI - STK-1 receptor gene is expressed in various human non-hematopoietic tumor cell lines--RT-PCR directed analysis of STK-1 mRNA expression. Preliminary report. AB - The aim of this study was to evaluate the presence of the mRNA for the hematopoietic STK-1 receptor in various human tumor cell lines using RT-PCR directed analysis of gene expression. We have found STK-1R mRNA to be expressed in non-hematopoietic malignant cells of ectodermal, endodermal and mesodermal origin confirms a hypothesis that STK-1R is similar to other receptors with intrinsic tyrosine kinase activity, is not for specific hematopoiesis and is also expressed in non-hematopoietic cells. The fact that STK-1R is detectable in different tumor cell lines should also inspire further studies to evaluate its role in the transformation and growth of malignant cells. PMID- 8209614 TI - Quality of plasma separated from (buffy coat + plasma). An alternative way of blood processing. AB - A CPD/ADSOL triple-bag system was used to produce plasma, buffy coat and resuspended erythrocytes. These components could be produced in a quadruple-bag system when working according to the conventional technique. In the experimental technique, buffy coat and plasma are transferred together into the satellite bag and are separated from each other only after the second centrifugation. The plasma complement system is not activated and factor IXa is not generated when applying the experimental technique. The quality of plasma meets the international requirements. The blood component processing technique using a triple-bag system is less expensive compared to the quadruple-bag one. PMID- 8209615 TI - [Acute undifferentiated and minimally differentiated leukemia]. PMID- 8209616 TI - [Myasthenic syndrome associated with relapse of Hodgkin's disease]. AB - Hodgkin's Disease in 12-years old boy was described. After 1-year remission, the relapse of disease localizes in the mediastinum occurred. At the same time myasthenic syndrome was diagnosed. During chemotherapy of H.D. relapse, symptoms of myasthenic syndrome regressed. PMID- 8209617 TI - [Myopathy as a first symptom in Hodgkin's disease]. AB - We present a case of Hodgkin's disease first symptom of which was paraneoplastic syndrome in a form of myopathy. It caused a delay in putting forward an appropriate diagnosis. PMID- 8209618 TI - Fludarabine therapy in a patient with progressive symptomatic Waldenstrom's macroglobulinemia. AB - A 66-year old female patient with symptomatic Waldenstrom's macroglobulinemia was treated with six courses of fludarabine monophosphate, which resulted in partial remission of the disease. Six months after completion of therapy IgM level decreased further and durable partial remission was confirmed. PMID- 8209619 TI - [Induction of hematologic remission in a patient with acute promyelocytic leukemia through the therapeutic use of trans-retinoic acid]. AB - A case of 62-year-old female with acute promyelocytic leukemia is presented, in whom in poor general condition, and with symptoms of severe haemorrhagic diathesis and biochemical signs of coagulopathy a treatment with trans-retinoic acid was induced. After three weeks of treatment with t-RA complete hematological and clinical remission was achieved, without bone marrow aplasia, worsening of hemostatic parameters, or necessity of protective or therapeutic antibiotics administration typical of conventional chemotherapy. Apart from skin allergization and increase of transaminases other side effects of the t-RA treatment were not observed. PMID- 8209620 TI - Anesthetic management of pheochromocytoma in a long term hemodialysed patient. AB - The anesthetic management of a hemodialyzed patient with a dopamine producing pheochromocytoma is described. A 56-years old man underwent surgical procedure the day after hemodialysis. Prior to intervention adrenal cortex hormones were normal as well as other endocrine variables (T3-T4-TSH-cortisol-ACTH-parathyroid hormone); epinephrine and norepinephrine, were in a normal range while dopamine was elevated (185 pg/ml). Preoperatively the patient was alpha-blocked with oral phenoxybenzamine (20 mg/day). A balanced anesthesia was performed (isoflurane and fentanyl). Plasma catecholamines were determined. During the induction of anesthesia and before tracheal intubation phentolamine and labetalol were injected till 3.4 mg and 50 mg total dose respectively. During surgical manipulation a nitroglycerin infusion was started (1.5 gamma/kg/min) and after tumor resection dopamine was given till 15 gamma/kg/min. Hormonal values increased in presence of unchanged hemodynamic parameters, likely due to alpha and/or beta blockade. In this case report our problem was especially fluid replacement after tumor resection, because of renal failure. On the basis of CVP and PCWP values, fluid treatment and dopamine infusion allowed to achieve an adequate preload. A sufficient level of analgesia and an efficient alpha blockade may assure hemodynamic stability also in a so compromised patient status. PMID- 8209621 TI - Massive ketonuria during sedation with propofol in a 12 year old girl with severe head trauma. AB - Severe ketonuria developed during sedation with propofol in a 12 year old girl with brain injury. Deep sedation with propofol (5.1 mg/kg/h) was required because of agitation and severe intracranial hypertension; as a part of our management protocol, glucose intake was restricted to 5 Kcal/h. After 18 hours of propofol infusion there was intense ketonuria (8+ by Ketostix) without any evidence of metabolic acidosis (pH, HCO3- and anion gap were within normal values). At this time, indirect calorimetry (Deltatrac) confirmed that energy expenditure was principally based on fat consumption (70% of energy expenditure). Lowering the propofol infusion rate and increasing glucose intake reduced fat consumption to 39% within 8 hours: at this time, Ketostix was negative for ketone bodies. This case illustrates a potential risk of ketonuria during prolonged sedation with propofol (a 10% solution of intralipid), particularly if glucose intake is restricted. Monitoring urinary ketone bodies is recommended under these circumstances. PMID- 8209623 TI - Transfusion depends on the doctor, not on the patient: the SAnGUIS Study of Transfusion in Elective Surgery in Europe. PMID- 8209622 TI - Malignant hyperthermia and severe hypoglycemia after reexposure to halothane. AB - A four year child presented with an episode of malignant hyperthermia induced by reexposure to halothane. The episode was associated with early onset of a severe hypoglycemia and liver enzymatic perturbances. Etiology of these perturbances is hard to state precisely in this clinical context, but a hepatic toxicity of halothane and/or by dantrolene is considered. PMID- 8209624 TI - The anesthesiologist and the law: the criminal liability of midwives and anesthesiologists for epidural anesthetic reinjection in obstetrics. AB - The issue whether an anesthesiologist can be criminally condemned for a mistaken injection by the midwife of a mixture of local anesthetics with calcium chloride into the epidural space was examined by the Criminal tribunal of Dendermonde and confirmed by the Court of Appeal of Ghent. Liability was asserted not only against the negligent midwife who did the erroneous reinjection, but also against the resident anesthesiologist who followed the rules of the anesthesia department and ordered the replacement of the syringe by telephone. The midwife was condemned not because she performed the technical act of an epidural reinjection, but because she made an obvious error in making the solution by confusing of diluting solution. The anesthesiologist was condemned because she did not directly control the midwife while she was performing her task. The current medico-legal situation in Belgium is paradoxical and even greatly inconsistent in that patients with no medical or nursing qualifications perform acts under the safety limits of the patient controlled epidural analgesia (PCEA) technique, acts which nurses or midwives are not legally permitted to perform. The author suggests that the law should be changed, allowing epidural reinjections and the replacements of the syringe of continuous epidural analgesia infusion by nurses or midwives on condition that the physician remains responsible for training and selecting his collaborators and that the injected dose does not exceed the safety limits of a spinal dose of the same anesthetic. PMID- 8209625 TI - [Characterization of chronic plantar ulcers in former leprosy patients]. AB - Between 1988 and 1992, 21 biopsies for pathological examination were taken from 20 Senegalese leprosy patients suffering from chronic plantar ulcers (CPU) suspected of malignant transformation. The diagnosis of squamous cell carcinoma was effectively made in 13 cases and that of pseudoepitheliomatous hyperplasia in the remaining 8 cases. The mean period of time between the onset of CPU and that of malignant transformation was 10 years (range: 1 to 15 years); the mean annual frequency of the malignant transformation was 2 per 1,000 CPU. In countries where pathological examination is not available, below knee amputation could be considered whenever main clinical signs of malignant transformation are present. In countries where pathological examination is available, the therapeutic decision may differ according to the diagnosis: below knee amputation supplemented with block dissection of inguinal lymph nodes whenever possible in cases of carcinoma; below knee amputation depending on the function status of the foot and on the volume of tumor in case of pseudo-epitheliomatous hyperplasia. PMID- 8209626 TI - [Apropos of a case of perforating, leprous plantar ulcer occuring at 15 years of age]. AB - Perforating ulcers of the foot occurring in leprosy are frequent, chronic, often giving mutilations. They usually affect the adult. Plantar ulcer occurred in a 15 year-old young patient affected by tuberculoid leprosy has incited us to report it. PMID- 8209627 TI - [An original experience through the creation of a new functional rehabilitation center for Vietnamese lepers]. AB - Since 1990, the creation of a Rehabilitation Center for Vietnamese leprosy patients under the aegis of "Oeuvres Hospitalieres Francaises de l'Ordre de Malte" is the result of emphasized collaboration between governmental and non governmental organizations, and between medical and paramedical specialists. This humanitarian action is not "a present home delivery". The end of this action is to set progressively a realist enterprise that depends on preliminary epidemiologic investigations on the spot to analyse means and necessities. Frequency of disabilities (49.6%) and predominance of grades 1 and 2 (83.5%) require aids. The realisation of technology transfer at all medical care levels is necessary. But at the same time, it is essential to build surroundings adapted infrastructure, to equip with effective material giving comfort and security for patients, and even to supply with pharmaceutic drugs in order to continue rehabilitation's activities. In short range, patient's selection and regular control give first objective results. PMID- 8209628 TI - [Leprosy. Bibliography]. PMID- 8209629 TI - MRI in focal lesions. AB - The advent of modern, high resolution MRI and post-processing techniques allows the identification of the underlying structural abnormalities in most (> 80%) patients with partial epilepsy undergoing presurgical evaluation. This information is crucially important for case selection, and the prediction of post operative seizure control. In consequence, the whole agenda of pre-operative assessment should change, with increasing emphasis on high quality neuroimaging. PMID- 8209630 TI - MR-scan and focal lesions. PMID- 8209631 TI - Mesial temporal sclerosis and volumetric investigations. AB - Volumetric MRI data acquisition permits reliable and accurate measurement of mesial temporal lobe structures. In normal subjects, these structures are very symmetric. A high degree of pathological specificity is associated with the finding of even minor volume asymmetries. Definition in this manner allows precise estimation of both absolute and relative volume differences, and precise anatomical localisation of volume loss within the hippocampus. There are good EEG and clinical correlates with the distribution of volume loss defined on MRI studies. Volumetric assessment is fast, reliable, non-invasive, and a relatively inexpensive component of the pre-operative work-up. It is the method of choice when imaging patients with clinical temporal lobe epilepsy undergoing pre surgical evaluation. The finding of significant hippocampal volume asymmetry in a patient with clinical temporal lobe seizures being evaluated for epilepsy surgery may obviate the need for alternative sophisticated, invasive, or expensive investigative procedures. At our centre, such MRI allows "fast track" cases to proceed to surgery without further invasive investigations, and is likely to have a dramatic effect on pre-operative evaluation in most centres practising epilepsy surgery. PMID- 8209632 TI - 1H magnetic resonance spectroscopy in the investigation of intractable epilepsy. AB - We have been using proton magnetic resonance spectroscopy (1H MRS) in the investigation of adults and children with intractable epilepsy. Spectra were obtained from 2 x 2 x 2 cm cubes in the medial region of the temporal lobe, and were analyzed on the basis of signals from N-acetylaspartate (NAA), creatine+phosphocreatine (Cr), and choline-containing compounds (Cho). In comparison with control subjects, the epilepsy patients as a group show significant reductions in the NAA signal and in the NAA/Cho+Cr ratio, with increases in the Cho and Cr signals. The reduction in NAA is interpreted in terms of neuronal loss or damage, while the increase in Cr and Cho signals may be a reflection of reactive astrocytosis. PMID- 8209633 TI - Utility of interictal SPECT of rCBF for focal diagnosis of the epileptogenic zone(s). AB - With Single Photon Emission Computed Tomography (SPECT) of regional cerebral bloodflow (rCBF) ictally and interictally, regional changes of rCBF can be detected in many cases with medically intractable complex partial seizures. Interictal SPECT shows abnormal rCBF in the epileptogenic temporal lobe in 40% to 85% of the patients. A critical survey of the methodological problems considering isotopes, scanners, data analysis and patient population is presented here as well as a few semi-quantitative studies including our own. It is concluded, that SPECT of rCBF is a useful, non-invasive method of localizing the epileptogenic zone in patients with severe partial focal epilepsy. Ictal SPECT of rCBF has a higher predictive value and is more sensitive than interictal studies for localization of the seizure focus. Interictal SPECT using a high-resolution system obtains an almost as high frequency of localization of the focus. With low resolution scanners, a minor frequency is observed. Both interictal and ictal SPECT recordings should be obtained for localization of the epileptogenic focus in presurgical cases as interictal hypoperfusion and ictal hyperperfusion demonstrated in the same focal area are highly characteristic of a seizure focus. PMID- 8209634 TI - Ictal brain imaging in presurgical evaluation of patients with medically intractable complex partial seizures. AB - At the Indiana University Medical Center, 99 patients with medically intractable complex partial seizures (MI-CPS) had presurgical evaluation with subsequent anterior temporal lobectomy. The majority of the patients had single photon emission tomography (SPECT) performed interictally as well as during an actual epileptic seizure (ictal scan). Decreased regional cerebral perfusion (rCP) was seen in 54/94 (57%) of the interictal scans corresponding to the eventual site of the surgery. However, ictal scans provided a higher yield; increased rCP in the temporal lobe during an actual seizure was observed in 60/82 (73%) concordant to the side of surgery. SPECT is a useful, noninvasive method of localizing the epileptiform focus in patients with MI-CPS considered for resective surgery. Both interictal and ictal SPECT need to be performed; combined interictal hypoperfusion and ictal hyperperfusion in the same focal area are unique to epileptogenic lesions. Ictal SPECT studies can be performed in the majority of patients during the period of continuous video/EEG monitoring with only a little additional effort. Combining the results of functional brain imaging (interictal and ictal SPECT, PET) with clinical semiology of seizures, surface and sphenoidal EEG, magnetic resonance imaging and other non-invasive tests, anterior temporal lobectomy can be recommended in approximately two-thirds of the patients without resorting to potentially dangerous intracranial EEG monitoring. PMID- 8209635 TI - Utility of ictal SPECT: peri-ictal, post-ictal. PMID- 8209636 TI - PET and functional testing in temporal lobe epilepsy. AB - Thirty-seven patients with severe temporal lobe epilepsy were studied interictally with [18F]fluorodeoxyglucose-PET in each of three conditions: resting, during emotional speech, and while performing a visual recognition task. In the resting state, each patient exhibited regional hypometabolism in agreement with his epileptic EEG focus, but that area was typically very large. The zone of maximum dysfunction was significantly better demarcated on activated scans showing an increase in whole-brain metabolism averaging 18%. Concurrently, the midtemporal-focus metabolic contrast was improved by 27%. This effect was more consistently produced by the speech paradigm that also induced significant amygdala recruitment and revealed the individual hemispheric speech dominance. Psychological trait factors played a role only for unspecific global activation. PMID- 8209637 TI - Methodological considerations. An overview of SPECT and PET. PMID- 8209638 TI - View of the brain through a flow-coloured time window. AB - Radioactive tracer substances administered to study cerebral functions open a time-dependent window to the brain. We can study e.g. regional cerebral blood flow (rCBF) or chemical properties such as receptors for transmitter substances. Since the tracer substance is carried by the blood flow into the brain its initial distribution will be proportional to the rCBF. The possibility to study more specific brain functions depends on the available time for redistribution of the tracer substance according to its specific chemical affinity. I have studied with the aid of a simple mathematic model the time needed for distribution and redistribution of freely diffusable tracer substances in the brain. The results indicate that SPECT measurements of brain receptor properties in theory give at least as good recording conditions as corresponding PET studies. Clinical SPECT receptor studies will presumably soon contribute to our knowledge of the epileptic pathogenic mechanisms. PMID- 8209639 TI - Visual inspection versus quantified analysis of functional brain images. PMID- 8209640 TI - Scalp EEG recording: interictal/ictal location and spreading of epileptiform events. AB - The relevance of scalp EEG recording on the selection of patients for epilepsy surgery usually is based on the concordance between the location of the epileptogenic focus and the presumed ictal origin of clinical seizures visually identified or video recorded. Bilateralisation and/or spreading of the epileptiform events are among the causes of the relative lack of agreement between scalp topography and origin of EEG potentials. Computer methods mainly if they are adaptive and use multistrategic approaches improve the accuracy on the detection of the epileptogenic focus, extracting relevant information on the location and spreading of epileptiform events. PMID- 8209641 TI - PET studies of patients with partial epilepsy: visual interpretation vs. semi quantification/quantification. AB - One of the advantages of PET is to allow for precise regional measurements of radioactive tracers in slices of brain. Furthermore, complex compartment modelling methods have been designed to transform the regional radioactive concentrations into biological units. The question is often raised whether quantification of PET studies is necessary in clinical practice. In epileptology, the regional biochemical changes associated with temporal lobe epilepsy are easily detected by experienced eyes and quantification is not required for diagnosis purposes. By contrast, inter-patient or inter-population comparisons can only be performed if regional measures have been obtained; if the PET method has been previously validated, simple measurements (regional activity) are sufficient and (kinetic) compartmental modelling is not necessary in routine. PMID- 8209642 TI - Epilepsy surgery: non-invasive versus invasive focus localization. What is needed from the neurosurgical point of view. AB - This paper discusses the place of non-invasive and invasive methods of investigation in the selection of patients for temporal lobe resection. Two series from the same department are compared and the relationship of the outcome to pathology is also discussed. PMID- 8209643 TI - What is needed for resective epilepsy surgery from a neurosurgical point of view? AB - Invasive versus non-invasive epileptogenic zone definition was analyzed in a series of 89 patients operated on for drug-resistant epilepsy. In the group of 69 cortical resections, 26% needed invasive recordings, 13.5% when foreign-tissue lesions had been detected by MRI and 32% when were absent. In this last group temporal resections had invasive EEG recordings in 23.5% versus 54.5% when the epileptogenic zone was extratemporal. In a group of 43 temporal resections with more than one year follow-up MRI has detected some abnormality in 84%. Excluding focal lesions, MRI detected hippocampal/temporal lobe atrophy in 66% of the cases in agreement with other noninvasive tests and in 4% contralateral to the epileptogenic zone located by subdural strips. The outcome analysis showed that 85% of the patients with MRI-EEG agreement were seizure free in contrast to only 43% when MRI was non-lateralizing. Future studies has to be oriented to better understand the epileptic process of patients without MRI abnormalities. PMID- 8209644 TI - Epilepsy surgery: non-invasive versus invasive focus localization. What is needed from a neurological point of view? AB - Epilepsy surgery should be performed as early as possible when intractable seizures are diagnosed together with a well-defined focus in a resectable part of the brain. All patients with epilepsy, and especially all children with epilepsy, should therefore be followed by a neurologist or a child neurologist specially trained in epileptology. PMID- 8209645 TI - Epilepsy surgery: non-invasive versus invasive focus localization. What is needed from the child neurologist point of view? PMID- 8209646 TI - Epilepsy surgery: non-invasive versus invasive focus localization. What is needed from a neuropsychological point of view. AB - This article discusses the neuropsychological aspects of surgery for epilepsy, and what is needed in EEG evaluation to permit the best use of neuropsychological data to help identify the most promising surgical candidates. Neuropsychological changes after surgery are first discussed, and it is noted that changes in memory are most important with less important fluctuations in intelligence and language and with other areas showing few or no changes. Emotional and psychosocial outcomes of surgery are dependent upon relief from seizures, with substantial relief being essential for improvement to be observed. Finally, it is noted that a combination of EEG and neuropsychological variables results in the best prediction of seizure relief, but reliable EEG data are critical to this effort. Obtaining such data frequently necessitates EEG monitoring, frequently with invasive electrodes. Such information often provides the clearest information and the best chance of assisting patients with epilepsy. PMID- 8209647 TI - Non-invasive localization of the epileptogenic focus by EEG dipole modeling. AB - Localization of epileptogenic foci by traditional visual inspection of EEG traces is simplistic. Voltage topography and subsequent spatio-temporal multiple dipole modeling are new techniques to assess the character of cerebral generators of EEG spikes and seizure rhythms. These predictions have been validated by intracranial monitoring. Patients with mesial temporal seizures have ipsilateral spikes and early ictal rhythms with a strong tangential (vertical) dipole component that often leads any radial source activity. This suggests propagation from baso mesial to lateral cortex. Those with infero-lateral temporal cortical seizures have similar findings, but tangential sources are synchronous with or lag radial sources. Patients with lateral temporal cortical seizures have spikes and ictal activity that are modeled principally by radial dipoles. PMID- 8209648 TI - Comments on neuropsychological evaluation of epilepsy surgery: are the tests sensitive enough? AB - Epileptic lesions often affect two of the most important functions in human behavior, memory and emotion. While cognitive functions, e.g, speech and memory, are normally carefully studied, emotional and psychosocial aspects of behavior are often overlooked in the pre- and postoperative evaluation of epilepsy patients. In my comment, I will address the need for methodological and theoretical refinement, especially regarding measurements of emotional and psychosocial aspects. In evaluating memory functions, a functionalistic approach is suggested; that is, in contrast to the entity view, studies should focus on the interaction between task demands and the available cognitive capabilities of the rememberer. We should develop a broad set of tests and demonstrate dissociations between different tasks that tap different capabilities and different memory systems: we should look for patterns of results rather than single scores. PMID- 8209649 TI - Epilepsy surgery from a health authority view point. PMID- 8209650 TI - From EEG source localization to source imaging. AB - A new functional imaging technique, "FOCUS", has been developed to transform the traditional scalp EEG into an image of source activities. The image is based on multiple spatio-temporal dipole models and consists of gross spatial patterns and source waveforms reflecting the estimated activities of the different brain regions. The application of the 'FOCUS' technique to the EEG in temporal lobe epilepsy revealed the presence of different activities at the basal and lateral aspects of the temporal lobe. The source waveforms showed propagation patterns consistent with subdural recordings which were not recognizable in the scalp EEG. PMID- 8209651 TI - EEG dipole localization: discussion. PMID- 8209652 TI - Foramen ovale and peg electrodes. PMID- 8209653 TI - "Semi-invasive" vs. invasive approaches for intracranial EEG and seizure monitoring in epilepsy. AB - When non-invasive studies fail to provide sufficient localising data to permit resective epilepsy surgery, intracranial seizure monitoring may have to be performed. Various techniques are available with specific advantages as well as disadvantages. "Semi-invasive" techniques, despite their name, remain essentially "invasive". The choice for a specific approach therefore should depend on the clinical problem in each individual patient rather than on theoretical preference. PMID- 8209654 TI - Foramen ovale and epidural peg electrodes. PMID- 8209655 TI - Subdural electrodes. AB - Physical aspects favour subdural registrations: as the solid angle under which a source is seen from a nearby electrode, the potential is large; there is no distortion by high impedence between source and electrode, nor by perpendicular short circuits; the frequency response is quasi-linear. Technical aspects and implantation strategy are outlined. Interictal and ictal ECoG patterns of diagnostical relevance and activation procedures are discussed. Advantages of subdural electrodes are: They provide detailed information on the epileptogenic zone, data on prognosis, are free of artefacts, allow electrical stimulation to determine eloquent cortex areas; by mathematical analysis methods the localizing power is increased. Disadvantages are: closed fields can be missed (recordable only by depth electrodes), in comparison to EEG, costs are considerably higher. Risks are practically absent with strip electrodes. In about half of the investigated patients, subdural electrodes were necessary to minimize the area of resection on a rational basis. PMID- 8209656 TI - Extracranial EEG work-up in epilepsy surgery: usefulness and limitations. AB - Extracranial interictal and ictal EEG provide essential information to diagnosis, seizure/syndrome classification and focus localization. Combined with structural and dynamic neuro-imaging and neuropsychological data, extracranial EEG will often provide sufficient information in preoperative work-up for temporal lobectomy. Ictal EEG recordings are essential to confirm the diagnosis and classification and, above all, to exclude patients with significant non-epileptic seizures from further surgical evaluation. The advantage of sphenoidal electrodes lies first and foremost in a more favorable signal/noise ratio, while their superiority to closely placed special scalp electrodes are more debatable. PMID- 8209657 TI - Subdural and intracerebral recording in presurgical evaluation of epilepsy. PMID- 8209658 TI - Subdural electrodes: discussion. PMID- 8209659 TI - Stereo-electroencephalography methodology: advantages and limits. AB - Since January 1990, 70 patients with medically intractable partial epilepsy underwent a stereo-EEG investigation in our center. We first described technical requirements, and gave an overview of the variety of the explored cerebral regions and implantation patterns realized, pointing out the low rate of morbidity (1.4%). The three-dimensional epileptogenic zone thus defined led to a tailored individualized surgical excision in 60 patients, while 9 are waiting for surgery and the remaining 1 has been excluded (1.4%). Conceptual and technical aspects of the stereo-EEG methodology were discussed in order to underline its peculiarities in the field of "depth recordings", and more generally among the broader group of "invasive" procedures. PMID- 8209660 TI - Discussion of stereoelectroencephalography. AB - Stereoelectroencephalography (SEEG) provides the neurosurgeon with crucial information for directing surgical strategies aimed at removing the epileptogenic foci. In lesional epilepsies the epileptogenic area does not necessarily correspond with the lesional area as defined by imaging techniques. In the case of good correspondence, lesion-directed surgery may be beneficial for the associated epilepsy even without the guide of presurgical SEEG. According to personal observation, this seems to be the case for epileptogenic cavernous angiomas, while for low grade gliomas the criteria for SEEG indication are still to be defined. The SEEG definition of the primary epileptogenic area is based on the detection of leading epileptic potentials by optimally placed depth electrodes. Experimental results demonstrate that epileptic discharges recorded from the hippocampus as the apparent leading phenomena may in fact result from subtle changes in excitability taking place upstream in the piriform cortex. This may lead to misjudgment of the location of primary epileptogenic areas unless suitable techniques of SEEG analysis are applied. PMID- 8209661 TI - Electrocorticography and stimulation. AB - Although acute electrocorticography (ECoG) is routinely used during epilepsy surgery there is little agreement as to its value nor criteria for its interpretation. Specific issues are reviewed on the basis of the literature and personal studies: does failure to resect the entire irritative zone prejudice seizure control, and are residual discharges predictive of failure; does activation of the ECoG by intravenous barbiturates provide information of clinical value; does intraoperative electrical stimulation help to improve localisation or avoid postoperative deficits; is the ECoG of value for monitoring functional procedures; can the value of ECoG be increased by new interpretive approaches? It is suggested that resection of the entire area of interictal discharge is not essential for satisfactory surgical outcome, but a distinction may need to be made between those discharging regions that function as pacemakers and those in which ECoG spikes appear secondarily. There is also evidence that, apart from any consideration of determining the area resected, the topography of epileptiform discharge may be predictive of pathology and surgical outcome. It is concluded that more detailed topographic and quantitative analysis of the ECoG is required before its value in planning surgery can be determined or objective interpretive criteria established. PMID- 8209662 TI - Magnetic source localization and morphological changes in temporal lobe epilepsy: comparison of MEG/EEG, ECoG and volumetric MRI in presurgical evaluation of operated patients. AB - Is MEG source analysis able to precisely locate the primary focal epileptic activity? 22 patients with pharmacoresistant temporal lobe epilepsy were recorded during presurgical evaluation simultaneously with multichannel MEG/EEG and invasive (subdural) electrodes to evaluate the increase of information gained by MEG concerning the localization of focal epileptic activity and lesions. With this systematic study it should become clearer how often MEG can establish a diagnostic bridge between function and morphology. In addition, MEG localization accuracy of focal epileptic activity was to be validated empirically by invasive EEG recordings and postsurgical outcome. Spikes in the MEG were used for magnetic source localization, and the result was combined with magnetic resonance imaging (MRI). All patients definitely suffered from temporal lobe epilepsy and revealed a structural abnormality in MRI. 17 patients with lesions in the temporal lobe were operated meanwhile and became markedly improved or seizure free. In 7 of 8 patients with a tumor and validated operation outcome, a very close correlation of the 3D-magnetic source localization and the border of the tumor in the brain was found (distance less than 10 mm). In 8 of 9 patients with a temporal/hippocampal atrophy and validated operation outcome, dipoles of epileptiform activity were located within the atrophic lobe.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209663 TI - Comment: MEG in the study of epilepsy. PMID- 8209664 TI - Problems with electrical signs of epileptic focal discharges recorded from the scalp. AB - From 1957-92, 3235 patients with chronic drug-resistant epilepsy were admitted and examined as candidates for surgery, in 639 classical resective intervention, removal of epileptic foci, was performed. In 101 patients other functional or disconnection surgery was performed. Based on this experience some problems and difficulties of bioelectrical investigation and localization of epileptic foci by scalp EEG recording are presented. PMID- 8209665 TI - MEG, EEG and ECoG: discussion. PMID- 8209666 TI - Transcranial magnetic stimulation. Its role in the evaluation of patients with partial epilepsy. AB - Transcranial magnetic stimulation (TMS) is a relative new method in the evaluation of patients with various neurological diseases. With the introduction of repetitive (rapid rate) transcranial magnetic stimulators (RTMS), it has been possible to apply cortical stimuli with a stimulus rate up to 100 Hz. The preliminary results with TRMS suggest that it may be used in the study of speech lateralization. Seizures have been reported in patients with partial epilepsy during TMS. In these cases it remains uncertain whether the seizures were induced by the TMS or coincidentally with it. Minor changes in paroxysmal activity have been reported in some patients. These data suggest, that TMS is neither sensitive nor specific as an activation procedure of the epileptic focus in patients with partial epilepsy. Seizures have been provoked using RTMS, but its use as a seizure-inducing method is not yet evaluated. PMID- 8209667 TI - The role of humoral immunity in endometriosis. AB - In many ways endometriosis represents yet another form of unexplained infertility. The disease is clearly associated with a decrease in fecundity and while in advanced stages of the condition this infertility can be attributed to tubal factors, in mild stages of the disease the cause for the decrease in fertility is unknown. As in unexplained infertility, we have suggested that the impairment in fertility is due to autoantibody abnormalities. Endometriosis patients exhibit the same immunologic profile as previously described in women with unexplained infertility and repeated pregnancy loss. In fact, endometriosis is not only characterized by unexplained infertility but also by repeated and excessive pregnancy wastage. Its clinical presentation mimics that of an autoimmune disease, raising the question whether endometriosis is, in fact, an autoimmune disease. Endometriosis demonstrates immunologic abnormalities not only in respect to autoreactivity. Abnormalities in immune function have been widely reported in reference to almost any lymphocyte and macrophage function and, once again, the similarity to findings in patients with unexplained infertility is blatant. Abnormalities can be found in peripheral blood and especially prominently in peritoneal fluid. Treatment of immunologic abnormalities, and especially of autoantibody abnormalities, restores a level of fertility in endometriosis patients. It has also been demonstrated, in an animal model, that non-specific immune modulation may improve fertility. PMID- 8209669 TI - Hormonal therapies for endometriosis: implications for bone metabolism. AB - The non-surgical treatment of endometriosis involves hormone therapy that either affects the lesions directly, or indirectly inhibits endometrial proliferation and induces atrophy through estrogen deprivation, or through a combination of these effects. The medications used to treat endometriosis are progestins (e.g. norethindrone, medroxyprogesterone acetate), oral contraceptives (e.g. estrogen progesterone acetate), androgens and their derivatives (e.g. danazol, gestrinone), and gonadotropin-releasing hormone (GnRH) agonists (e.g. buserelin, leuprolide acetate, nafarelin, goserelin, tryptorelin). Agents such as GnRH agonists that produce sustained and prolonged hypoestrogenemia, similar to the postmenopausal hypogonadal state, can have a significant negative impact on trabecular bone mass. Evidence from the use of oral contraceptives and medroxyprogesterone acetate indicated that they had no apparent adverse effect on bone mass. Initial studies with dual-photon absorptiometry were unable to detect any appreciable bone loss with GnRH agonists. Later studies, however, have invariably found significant bone loss as early as 3 months after the start of treatment. Quantitated computerized tomography always shows significant trabecular bone loss of the vertebrae and hip with GnRH agonists. Depot preparations appear to produce more marked loss than daily intranasal sprays. Recovery of bone loss may take 6-12 months after the end of therapy, with considerable individual variations. In contrast, treatment of endometriosis with danazol produces bone gain. If endometriosis has to be treated with bone depleting agents, prevention or attenuation of bone loss using combined therapy with progestins, etidronate or calcitonin together with GnRH agonists should be considered; however, further studies are necessary to define the efficacy of such combined therapy. Smoking and excessive caffeine intake should be avoided. The risk of bone loss should be considered when choosing the appropriate management of endometriosis, the selection of patients, repeat therapies for recurrent endometriosis, and the formulation of such therapies, in order to minimize or overcome it. PMID- 8209668 TI - New principles in the management of endometriosis. AB - The current management of endometriosis includes expectant, medical, surgical and combined therapies and the selection is based on the staging of the disease proposed by the American Fertility Society (AFS). This approach, however, has proven to be inadequate for the selection of medical treatment. Peritoneal endometriosis represents a range of lesions of different activity and stage of evolution. Surgical resection carries a risk of adhesion formation. Two to three months of medical therapy can induce inactivation and regression of active lesions. These factors should be taken into account in the selection of therapy. Ovarian endometrial cysts are indications for reconstructive surgery. The extent of adhesions and fibrosis, rather than the size of the cyst, determine the surgical outcome. The invaginated cortex explains the frequent association with lutein cysts. Large cysts can be conservatively treated at laparoscopy in a three step procedure with a 3-month medical therapy between the first and second laparoscopy. Deep nodular endometriosis presents different lesions varying from fibrosis to adenomyosis. The effect of a therapeutic medical trial can be evaluated within 2 months. Different modalities are available for long-term medical therapy. Surgical resection is the treatment of choice for the adenomyosis type. PMID- 8209670 TI - Action of danazol on plasma lipids and lipoprotein metabolism. AB - Danazol, a weakly androgenic, heterocyclic compound with anabolic properties, is used primarily in the treatment of endometriosis and other gynecological complaints. Early reports indicated that the drug had little effect on plasma lipid (cholesterol and triglyceride) levels but recently concern has been expressed over more subtle changes reported in plasma lipid and lipoprotein metabolism after danazol treatment. Therapy produces a rapid reduction in high density lipoprotein (HDL) cholesterol (particularly in the putatively cardioprotective HDL2 subfraction) coupled with a rise in the pro-atherogenic low density lipoprotein (LDL). These apparently unwanted actions are balanced against a possibly beneficial reduction in the atherogenic lipoprotein(a) fraction. The mechanism of these changes induced by danazol is unknown but probably relates to effects on hepatic lipase, LDL receptor and lecithin cholesterol acyl transferase activity. While it is prudent to recognize the potential detriment that may follow these perturbations, concern is only warranted where therapy is prolonged (> 12 months) or given to subjects with a high background risk of ischemic heart disease. PMID- 8209671 TI - Endometriosis classification for infertility. AB - The American Fertility Society (AFS) classification for endometriosis is a widely used system for categorizing the severity of pelvic endometriosis. Although this classification represents a detailed description of the location and extent of disease, it has limitations when used to predict fecundity following treatment of the different stages of endometriosis. Concern regarding the inability of the AFS classification to discriminate between mild, moderate and severe disease in terms of pregnancy outcome is related to arbitrary assignment of point scores for each pathologic observation, and to arbitrary assignment of total scores to patients divided into severity categories. Establishment of empirically-derived scores for individual pathologic observations and identification of cut-off scores based on pregnancy outcome for each category would offer a reliable, clinically useful classification system for endometriosis in infertile women. PMID- 8209672 TI - The role of cell-mediated immunity in pathogenesis of endometriosis. AB - It is well recognized that cell-mediated immune responses contribute to the elimination of foreign antigens and cells from the invading organism. It is also likely that the immune system can recognize and eliminate altered or misplaced autologous cells such as ectopic endometrial cells. This mechanism may be operative in most women, preventing the development of endometriosis. Recent studies in women with endometriosis demonstrate functional changes in cells of the immune system including monocytes/macrophages, natural killer cells, cytotoxic T-lymphocytes and B cells. These changes suggest decreased surveillance, recognition and destruction of the misplaced endometrial cells and possible facilitation of their implantation and development of endometriosis. Peripheral blood monocytes (PBM) and peritoneal macrophages (PM) may play a key role in this respect, and may control the function of other immune cells. We have demonstrated that in normal fertile women without endometriosis, PBM and PM suppress endometrial cell proliferation in vitro. In endometriosis, PBM stimulate and PM inhibit endometrial cell proliferation and the cytotoxic effect of PM is inversely correlated with the stage of the disease. The decrease in PM cytotoxic function is controlled by prostaglandin synthesis. In infertile women without endometriosis, the effects of PM and PBM are variable. In about one third of patients, the effects of PM and PBM suggest subclinical endometriosis; in the remaining two thirds of patients the effects of PM and PBM are similar to those of fertile controls. Interestingly, endometrial cells in women with endometriosis are more sensitive to the stimulatory effect of PBM, and more resistant to the cytotoxicity of the immune cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209673 TI - Perinatal and infant mortality: trends and risk factors in Norway 1967-90. AB - Neither the infant nor the under 24 hours mortality rates in Norway improved in the 1980s. The late neonatal mortality rate did not improve significantly in either the 1980s or the 1970s. The postneonatal mortality rate rose steadily throughout the last 15 years. The major mortality declines for all age groups took place in the 1970s. In the 1980s, only the 1-7-day mortality improved significantly. As a result, Norway fell behind in the international ranking of perinatal and infant mortality. Disparities among the perinatal mortality rates of Norwegian counties diminished throughout the 1970s. In the 1980s, the county disparities intermittently increased. Postneonatal deaths represented an increasing proportion; in the late 1980s, they amounted to half of the infant deaths and one-third of the total perinatal and infant deaths. In 1988, the postneonatal mortality rate was about twice as high in Norway as in Finland, Iceland, or Sweden. Birth injuries and infections almost disappeared as causes of perinatal and infant death. Other perinatal causes also diminished substantially. The incidence of congenital anomalies remained stable. The incidence of sudden infant death syndrome (SIDS), the single cause with continuous rate rise, more than doubled. In the late 1980s, SIDS caused one-quarter of the infant and more than half of the postneonatal deaths. The share of perinatal deaths from placentoumbilical causes (mostly placenta previa and abruptio placentae) and maternal diseases increased substantially. The affluence of Norway surged in the late 1970s and the 1980s, but health care was not given a higher priority. About 80% of fertile women used contraceptives. The use of modern methods increased substantially; oral contraceptives, in particular. About 60,000 confinements and 15,000 legally induced abortions took place in Norway each year. The number of induced abortions increased in women in their twenties, but decreased in all other age groups. As the total fertility decreased, each woman, on average, gave birth to 1.9 children and experienced 0.5 legally induced abortion. Maternal mortality was reduced to nil. Fewer marriages were contracted, and the divorce rate more than doubled. As a result, more than 35% of all births now occur out of wedlock, as compared with 5% in the late 1960s. The individual importance of birth out of wedlock as a risk factor has been reduced substantially. The mean maternal age increased from 26 to 28 years. The proportion of births by teenage mothers dropped from 8 to 3%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8209674 TI - Clinical approach to the dysphagic patient. AB - Dysphagia is a symptom of disease reflecting either structural or neuromuscular disorders of the oropharynx or esophagus. Dysphagia should be distinguished from globus sensation and odynophagia. The clinical evaluation of the dysphagia patient by the otolaryngologist requires taking a detailed history of the complaint, extended ENT physical examination, fiberoptic nasopharyngolaryngoscopy, to assess the oral and pharyngeal phases of swallowing. Special investigations including radiography, esophageal endoscopy, ultrasonography, pH metry, manometry may be needed for the full diagnosis. It is essential for the otolaryngologist to develop a close working relationship with the radiologist, gastroenterologist, neurologist and swallowing therapist. This team approach will allow in most of the patients with dysphagia not only to identify the cause of the complaint but also to implement an effective treatment. PMID- 8209675 TI - The radiologic investigation of dysphagia. AB - The fundamentals of the radiologic investigation of dysphagia using barium are described. Emphasis is given on videofluoroscopy. The clinical perspective of the dysphagic patient as well as the methods of examination are described. Results are exposed in terms of functional and structural analysis. Some examples of common normal and pathological findings are given. PMID- 8209676 TI - Non-imaging techniques for the study of swallowing. AB - A number of non-imaging procedures have been used to study various aspects of swallow physiology including electromyography, electroglottography, manometry, the sounds of swallow, and the blue dye test. Each of these techniques is described according to the typical procedures used, the types of information produced and advantages and limitations when applied to the study of oropharyngeal swallow. For most accurate interpretation, the majority of these techniques are used concurrently with imaging procedures such as videofluorography. PMID- 8209677 TI - Dysphagia associated with neurological disorders. AB - Neurogenic dysphagia results from sensorimotor impairment of the oral and pharyngeal phases of swallowing due to a neurologic disorder. The symptoms of neurogenic dysphagia include drooling, difficulty initiating swallowing, nasal regurgitation, difficulty managing secretions, choke/cough episodes while feeding, and food sticking in the throat. If unrecognized and untreated, neurogenic dysphagia can lead to dehydration, malnutrition, and respiratory complications. The symptoms of neurogenic dysphagia may be relatively inapparent on account of both compensation for swallowing impairment and diminution of the laryngeal cough reflex due to a variety of factors. Patients with symptoms of oropharyngeal dysphagia should undergo videofluoroscopy of swallowing, which in the case of neurogenic dysphagia typically reveals impairment of oropharyngeal motor performance and/or laryngeal protection. The many causes of neurogenic dysphagia include stroke, head trauma, Parkinson's disease, motor neuron disease and myopathy. Evaluation of the cause of unexplained neurogenic dysphagia should include consultation by a neurologist, magnetic resonance imaging of the brain, blood tests (routine studies plus muscle enzymes, thyroid screening, vitamin B12 and anti-acetylcholine receptor antibodies), electromyography/nerve conduction studies, and, in certain cases, muscle biopsy or cerebrospinal fluid examination. Treatment of neurogenic dysphagia involves treatment of the underlying neurologic disorder (if possible), swallowing therapy (if oral feeding is reasonably safe to attempt) and gastrostomy (if oral feeding is unsafe or inadequate). PMID- 8209678 TI - Dysphagia associated with pharyngoesophageal segment dysfunction. AB - This paper deals with pharyngoesophageal segment dysfunction in swallowing. The mechanisms of normal opening of the PE segment is discussed. Problems in evaluation of the PE segment are presented. Examples of various etiologies of PE segment dysfunction are discussed. PMID- 8209679 TI - Dysphagia secondary to head and neck cancer surgery. AB - This paper deals with swallowing abnormalities associated with the resection of cancers of the head and neck. The different sites of resection and the effects on swallowing as documented by modified barium swallow and manofluorography are described. Recommendations are made for the most functional types of reconstruction based upon the experience of the senior author. PMID- 8209680 TI - Esophageal dysphagia. AB - This paper is a review of esophageal anatomy, physiology and pathophysiology. The diagnosis and therapy of benign and malignant esophageal strictures are discussed including the specifics of esophageal dilation and tumor ablation procedures. The diagnosis and therapy of esophagitis in the immunocompromised (HIV, chemotherapy, transplant recipient) host is discussed. The pathophysiology and treatment of achalasia and esophageal spasm are reviewed. Finally, current concepts of the pathophysiology and therapy of gastroesophageal reflux disease. Emphasis is placed on the dual sphincter theory of gastroesophageal junction competence and the need for maintenance anti-secretory therapy. PMID- 8209681 TI - Dysphagia with systemic diseases. AB - When a patient presents with dysphagia, the physician generally expects to find a local cause for the patient's complaint. Although local causes can explain many of the patient's swallowing difficulties, diseases that affect more than one organ or organ system may manifest as first or accompanying symptom of this "systemic disease". This article attempts to give an as complete as possible overview of these systemic diseases. Blood and immunologic, cardiac, dermatologic diseases, diabetes, drugs, gastroenterologic and pulmonary diseases, sarcoidosis, systemic disorders and webs will be discussed. Aging, not really a disease but a physiological phenomenon, will also be discussed because of repeated complaint of dysphagia in the elderly. Neuromuscular disease, cancer and the immunocompromised patient will not be included in this paper as they are presented by other authors in this report. PMID- 8209683 TI - Rehabilitation of oropharyngeal swallowing disorders. AB - Patients with oropharyngeal swallowing disorders can be rehabilitated through a program of radiographic assessment to define the patient's anatomic or physiologic swallowing disorder(s), followed by use of carefully selected compensatory and/or therapeutic strategies. Compensatory strategies are designed to eliminate symptoms of swallowing disorders, i.e., aspiration and inefficient swallow, and include postural changes, enhancement of sensory input, changes in food characteristics (viscosity, temperature, taste), modifications in volume and speed of food presentation, and intraoral prosthetics. Therapeutic strategies are designed to change swallow physiology and include range of motion exercises, sensory motor integration procedures and swallow maneuvers. The effects of many of these procedures can be assessed during the radiographic diagnostic procedure, once the patient's oropharyngeal anatomy and swallowing physiology have been defined. In general, swallowing assessment should be completed as soon as the patient is identified as dysphagic, and an appropriate rehabilitation plan initiated. PMID- 8209682 TI - Dysphagia in infants and children. AB - The history and physical examination provides in most patients sufficient information regarding the aetiology of dysphagia in childhood. However, dysphagia might in some rare cases be a diagnostic challenge, as e.g. in patients with gastro-oesophageal disease without typical oesophageal symptoms (regurgitation, emesis). In this paper, most interest will be given to these conditions causing dysphagia in whom the history and physical examination are less relevant. The percutaneous endoscopic gastrostomy offers new therapeutic possibilities. Perhaps more than in adults, a correct assessment of dysphagia in childhood necessitates a close collaboration between different sub-specialists such as a paediatric oto rhino-laryngologist, neurologist, pneumologist and gastro-enterologist. PMID- 8209684 TI - Surgical treatment of oropharyngeal swallowing disorders. AB - The objectives of the surgical treatment of oro-pharyngeal swallowing disorders is (1) to improve the impaired transport of the bolus, and (2) to prevent aspiration or control it to safe levels. In this overview the common surgical procedures to improve the specific oro-pharyngeal swallowing disorders are presented. The indications, advantages and disadvantages of each surgical technique are discussed. PMID- 8209685 TI - Nutritional aspects of dysphagia. AB - Adequate nutritional support is essential in the management of the dysphagic patient. In this article we discuss the indications, advantages and limitations of different types of oral and artificial feeding schedules. PMID- 8209686 TI - Multidisciplinary management of dysphagia. AB - Multidisciplinary management of dysphagia ensures that the dysphagic patient receives careful, in-depth assessment and treatment/rehabilitation of their swallowing disorders, and of its underlying etiology. Members of the team usually include the speech-language pathologist (swallowing therapist), gastroenterologist, radiologist, otolaryngologist, neurologist, pulmonologist, pharmacist, dietitian, occupational therapist, and physical therapist. Depending upon the setting, a pediatrician, physical medicine physician (physiatrist) or gerontologist may also be on the team. Respiratory medicine and nursing are usually also involved, as is the feeding staff. Respect for each other's expertise and easy communication between members of the team are crucial to success. Team operations should be continuously monitored for their overall efficacy and cost effectiveness. PMID- 8209687 TI - Anatomy, physiology and pathophysiology of dysphagia. AB - This is a review paper examining the pathogenesis of oropharyngeal dysphagia. Pharyngeal anatomy and physiology are discussed along with a detailed description of the neuronal architecture and function of the medullary swallowing center. The oropharyngeal swallow is then examined in biomechanical terms emphasizing that the swallow is comprised of several elements (velopharyngeal closure, upper esophageal sphincter opening, closure of the laryngeal vestibule, tongue loading, tongue pulsion and pharyngeal clearance) each of which can be compromised, causing dysphagia. The key modality for evaluating patients with oropharyngeal dysphagia is the videofluoroscopic swallowing study which is analyzed according to the efficacy with which these functional elements of the swallow are accomplished. Specific therapy can then be addressed toward correcting dysfunctional elements. PMID- 8209688 TI - [Recovery from Meniere's disease]. AB - When vertigo attacks and balance disorders stop, menieric patients are generally considered recovered although they complain of more or less severe sensorineural hearing loss. As far as a true clinical recovery is concerned, the Authors think that it should correspond not only to absence of vertiginous spells but even to a long lasting normal and stable hearing level. On the basics of this presumption, they select the files of 7/207 patients showing complete recovery since not less than 8 years. Age at the onset of the disease, associated disease, isolated symptoms before the appearance of the classic triade, age at the first attack, total number of crises, length of active period of the disease, maximum hearing loss, shape of audiometric tracing are all analyzed. Healed patients are characterized by a smooth evolution, which reverses in the very first phases of the disease, as well as by the following: 1) absence of head injury and viral labyrinthitis in clinical history; 2) onset of disease with complete symptomatology; 3) slight hearing loss and up-sloping audiometric configuration; 4) few attacks of vertigo (less than 30) lasting no longer than 12 hours; 5) active period of disease not exceeding 18 months. Recovery from Meniere's disease seems possible as long as labyrinth lesions are not stabilized. PMID- 8209689 TI - [Evoked otoacoustic emissions in noise-induced hearing loss]. AB - The Authors evaluated patterns of click-evoked otoacoustic emissions (EOE) in a group of 184 patients exposed to noise in their working environment. The aim of the study was to detect changes in EOE patterns in this group compared to the EOE of healthy subjects. The clinical history of each subject was recorded and otoscopy, pure tone audiogram and impedance tests (tympanometry, stapedial reflex threshold) were carried out in all patients. Noise-induced hearing loss found in 97 patients, unilateral sensorineural hearing loss in 17, other hearing disorders in 24 and normal auditory threshold in 46. EOE recording was carried out in the group of patients with noise-induced hearing loss (97), in the group with normal threshold (46) and in a control group of 15 healthy subjects. EOE recording was obtained using the ILO 88 Otodynamic Analyzer. We introduce a probe into the external ear canal using a non-linear click stimulus (intensity at approximately 85 dB spl) at a 20/sec. rate with a 20 msec. window. Normal EOE were found in the control group. Abnormal EOE were found in 79 cases (81%) of the noise-induced hearing loss group, and in 22 (48%) of the normal threshold group. These data show that noise-exposed subjects have alterations of EOE such as threshold shift missing frequency bands, even in absence of an auditory threshold shift. When EOE were present, the frequency spectrum often showed lack of emissions at high frequencies. This study confirms that cochlear exposure to noise may produce significant alterations of EOE and that this test may be considered highly sensitive in detecting early cochlear damage in chronic acoustic trauma. Therefore, EOE may be used in screening and follow-up of high risk populations such as noise-exposed subjects. PMID- 8209690 TI - [Value of TC99m-Nanocolloid spect in diagnosis and follow-up of necrotizing external otitis]. AB - Necrotizing external otitis (NEO), or malignant external otitis, a severe penetrating infection of the ear canal and the temporal bone, which occurs almost exclusively in diabetic or immunodepressed elderly patients, is caused in most cases by Pseudomonas aeruginosa while Staphylococcus epidermidis and Aspergillus fumigatus have been described as other possible agents. Recently bone scintigraphy, carried out above all employing SPECT, has been considered an important tool in diagnosis and follow-up of NEO. Many Authors confirm the role taken by Technetium99m-methylene-diphosphonate (MDP) and Gallium67-citrate bone scanning. Benecke suggested that response to therapy could be monitored with Ga67 or In111 scans. Two cases of NEO in which diagnosis and follow-up were made using Tc99m-nanocolloid (NC) SPECT are presented in this paper. The Authors discuss the advantages of this latter radiotracer, compared to those obtained with Ga67 citrate, in the follow-up evaluation of therapy efficacy. Tc99m-NC, in fact, is a better inflammation index in that its fixation on bone tissue is determined by the permeability of the basal membrane of vessels. Furthermore, with Tc99m-NC antibiotic therapy may be continued as long as necessary. Bone scintigraphy with other radiotracers may infact result positive for a long period after disease remission in that their fixation is linked to the one remodelling process. PMID- 8209691 TI - [Anaerobic cervical cellulitis: a therapeutic approach]. AB - The possibility of life-threatening complications arising from cervico-facial infections is well known. Deep cervical infections, however, rarely spread to the mediastinus. Organisms responsible for these infections usually include either aerobic or anaerobic microorganisms, whose synergistic activity provokes virulence and contributes to the violent nature of infection. Prompt recognition is vital if appropriate treatment is to be given. Initial management of deep-neck infections consists in intensive parenteral antibiotic therapy. Nevertheless, in spite of antibiotic therapy, mortality due to suppurative mediastinitis remains high. The Author emphasizes the importance and gives priority to surgical drainage and debridement, another fundamental part of treatment. PMID- 8209692 TI - [Nasopharyngeal carcinoma: multidisciplinary treatment]. AB - One hundred and twenty-eight cases of nasopharyngeal carcinoma treated at National Cancer Institute of Naples from 1980 to 1992 were retrospectively studied in order to evaluate the effectiveness of radio and chemotherapy. The histological types were the following: 75 cases of undifferentiated carcinoma, 49 cases of squamocellular carcinoma, 3 cases of lymphoma and 1 case of chordoma. Four cases were classified as Stage I (UICC 1977), 10 cases Stage II, 30 cases Stage III and 84 cases Stage IV. The patients were classified in four groups in relation to the treatment given: group A: 46 patients treated with radical radiotherapy alone; group B: 45 patients treated with radiotherapy and adjuvant chemotherapy (VCA); group C: 13 patients treated with neoadjuvant chemotherapy (CABO); group D: 24 patients treated with alternating radio-chemotherapy (CDDP 5FU) in the period between 1990-1992. The overall actuarial survival rate in all groups was 59% at three years and 52% at five years. There was a significative difference in survival actuarial rates between group A and B: the three-year survival rate was 54% in group A vs 46% in group B and the five-year survival rate was 43% vs 35%. In group D complete remission was obtained in 62.5% of the cases and partial remission in 25% of the cases. In conclusion the use of chemotherapy in combination with radiotherapy appeared to significantly increase the chance of long-term survival and probable healing. PMID- 8209693 TI - [Cytogenetic patterns in Warthin tumor]. AB - Our systematic studies of different types of benign and malignant salivary neoplasms in humans were initiated about two years ago. Analysis of karyotypes revealed that virtually all tumors are associated with chromosomal abnormalities. That those abnormalities may also take part in tumor initiation and progression is suggested by the association of specific chromosome rearrangement with particular cancers. We here with report cytogenetical observation in five Warthin's tumors giving particular attention to the possible occurrence of cells with (a) a normal karyotype or with (b) numerical changes, either loss of the Y chromosome or monosomy 4. The present series od adenolymphomas was karyotyped by a direct chromosomal analysis method. The method reported was highly successful, in several types of tumors showing the possibility of having good banded metaphases. All Warthin's tumors showed stemline (S) with a normal karyotype. These normal cells constituted the only S in two cases and the primary S in the other three cases. The normal cells observed in all adenolymphomas could be interpreted as outgrowing stroma cells. Most types of previously well-studied benign human tumor types, however (meningiomas, pleomorphic adenomas, lipomas), has a S group with a normal karyotype, regardless of the the tissue culture technique used. Thus, we believe that these normal cells usually represent neoplastic elements. Furthermore, we think that all benign tumors originate with a rather normal S, which, however, as the first indication of neoplastic transformation, shows chromosomal instability, such as the loss of chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209694 TI - [Mucoepidermoid carcinoma of salivary glands: histologic grading as prognostic factors]. AB - Mucoepidermoid carcinomas (MEC) make up 32% of the heterogeneous cases of malignant epithelial neoplasm of salivary glands observed in our Department. From 1980 to 1990, 270 patients with salivary gland tumefaction, which had previously been treated surgically, were studies. Thirty-four proved to be cases of malignant epithelial neoplasms while 12 oh these 34 were MEC. The biological behaviour of MEC appears to be closely linked to histological grading: a tumor with a low grading has good prognosis while in the case of tumors with a high grading there is a rapid development of local as well as distant metastases. At appears that, with regard to malignancy, localization is an important factors as well submandibular neoplasms are more aggressive the other cancers, probably because they attack periglandular tissue so promptly. PMID- 8209695 TI - Does the attentional state determine processing dominance in to-be-ignored compound stimuli? AB - Previous studies (Paquet, 1992, 1994; Paquet and Merikle, 1988) have shown that identification of the local aspect of an attended compound stimulus is delayed by the presence of global distractors within a to-be-ignored compound stimulus, whereas identification of the global aspect is unaffected by local distractors. This asymmetrical pattern of interference indicates that processing of to-be ignored compound stimuli is characterized by global dominance. In this study, I investigated the hypothesis that these findings were the outcome of subjects adopting an attentional state which favoured processing of global information. Following a procedure developed by Ward (1982), subjects were asked to perform two consecutive identification judgments of the global or the local aspects of two successive relevant compound stimuli, each presented with a to-be-ignored compound stimulus. The first and second judgments were performed either at the same level (i.e., both global or both local), or required switching attention across levels (i.e., global on the first judgment and local on the second, or local on the first judgment and global on the second). The results confirmed that the attentional state (switched vs. unswitched) influences global/local processing speed on the second judgment (Ward, 1982). However, no evidence for local dominance was found when the attentional state favored processing of local information. Instead, global distractors always affected local target identification, whereas interference effects of local distractors upon global target identification were restricted to the attention switching conditions. These findings suggest that the pattern of dominance in to-be-ignored stimuli is not determined by the attentional state, but may be related to fundamental differences in the strength of global and local information channels. PMID- 8209696 TI - Personality in Anorexia nervosa: an update and a theoretical integration. AB - No single cause is likely to be of supreme importance in the etiology of Anorexia nervosa, but personality factors continue to attract researchers' attention. This paper is a review of evidence on the subject, covering psychometric, interview, and projective investigations. Significant methodological problems exist in the literature, but do not suffice to explain findings of obsessive and inhibited features intermixed with impulsivity, and a high prevalence of defined personality disorders. Adding to previous work by Cloninger and Strober we suggest that vulnerable individuals are temperamentally incapable of coping with the challenges of adolescence by anything other than repetitive, reward seeking behavior. In a social environment that greatly emphasizes thinness as a criterion for self-worth and success, the outcome may be Anorexia nervosa. PMID- 8209697 TI - [The diagnostic game]. PMID- 8209698 TI - [Medical education and science]. PMID- 8209699 TI - [The health-media relationship]. PMID- 8209700 TI - [Urinary tract infections. The causative agents and their sensitivities to chemotherapeutic drugs]. AB - A retrospective study was made of the requests for bacteriological examination of urine samples by the different clinical departments of Vila Nova de Famalicao District Hospital, between July/89-June/90 and July/91-June/92. We were interested in assessing the spectrum of occurring micro-organisms in urinary tract infections, their antibiotic susceptibility, especially to those more frequently used in clinical practice in this institution and their evolution in time. In conclusion, the prevalence of isolated pathogens was quite similar to the spectrum published by other authors for a hospital population. No significant variation was found in the bacterial population between the two periods analysed, if we exclude the great increase in coagulase-negative staphylococci. In terms of benefits/costs/resistance, we concluded that the best antibiotic for the beginning of therapy in this Hospital is cotrimoxazole. Good choices were also quinolones, third-generation cephalosporins or aminoglycosides, but with the disadvantages of greater cost for the first two and toxicity for the last. PMID- 8209701 TI - [Intestinal obstruction. The experience of the Emergency Service of S. Jose Hospital 1981-1991]. AB - The results of 3679 patients, with intestinal obstruction, submitted to emergency surgery at the UUC-HCL between November 1981 and November 1991, were analysed in a general way, with the use of a graphic presentation. In the mechanical group, hernia (1604 cases), adhesions and bands (568 cases) and cancer (713 cases) were the most common pathologies; intestinal ischaemia (143 cases) was the most frequent form in the neurogenic group. Surgical therapy was evaluated in a general way. However, we comment on the evolution of primary surgical treatment of colorectal cancer in obstruction (625 cases). The mortality rate was in general: 10.8% (adults). In relative terms, the main features were intestinal ischaemia (39%), cancer (23%) and intestinal volvulus (22%). PMID- 8209702 TI - [Hemodialysis with bicarbonate 30 mEq/l versus 34 mEq/l and acetate: better hemodynamic tolerance and electrolyte and acid-base homeostasis]. AB - The use of bicarbonate buffer in dialysis is more physiological than acetate. The aim of this prospective study was to compare the hemodynamic stability, acid-base and electrolyte balance changes in a group of 5 hospital hemodialysis (HD) patients, with 3 different dialysis fluids: one with 30 mEq/l of bicarbonate (B30), another with 34 mEq/l of bicarbonate (B34) and the last with acetate (ACE). All the patients had more than 12 months in HD. Each patient had HD treatment with one of the 3 different dialysis fluids: ACE, B30, B34. Each HD had a duration of 4 hours, with less than 5% dry weight ultrafiltration (UF) and continuous cardiac monitoring. The following clinical and laboratory data were evaluated: arterial blood pressure (BP), cardiac rate (CR), respiratory rate (RR), cardiac arrhythmias, blood urea, creatinine, sodium, potassium, magnesium, total calcium (Ca), ionised calcium (Ca++), pH, bicarbonate (HCO3-) and pCO2. Statistic analysis was performed using Student's paired t test and ANOVA with Bonferroni correction. Clinical evaluation showed a CR increase only in the ACE group (pre X = 78.4 to 4 degrees h X = 102.6 p < 0.001). Analytical results demonstrated, at the 1st h, Ca++ stability in the B30 group; in the first 30' the pH decreased in the ACE group (pre X = 7.35 to 30' X = 7.34); during HD, HCO3- was not corrected in the ACE group (pre X = 19.4 to 4th h X = 20.0); at 4th, pCO2 also decreased in this group (pre X = 34.5 to 4th h X = 28.4 p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209704 TI - [Coma with miosis and bradycardia]. AB - The authors report a clinical case of clonidine poisoning in a 20-month-old child. Although a paradigmatic case, due to extensive symptomatology, it presented a diagnostic and therapeutic challenge. PMID- 8209703 TI - [Acute alcoholic hepatitis complicated by cardiac arrhythmia. Alcohol, hepatitis, hypomagnesemia, torsades de pointes, corticotherapy]. AB - The authors present the case of a 32-year-old woman, with acute alcoholic hepatitis(AAH), severe ionic changes and ventricular tachycardia torsade de pointes. Treatment with magnesium sulphate and the use of corticotherapy for AAH are the subjects for discussion. PMID- 8209705 TI - [The transjugular intrahepatic portosystemic shunt]. AB - The case of a 66-year-old woman with several episodes of hemorrhage by esophageal varices and ascites due to portal hypertension is presented. Despite 4 sessions of endoscopic sclerotherapy bleeding recurred. A transjugular intrahepatic portosystemic shunt was performed. In the 10 months following the intervention, there was no further hemorrhage, the ascites disappeared and the shunt is open. PMID- 8209707 TI - [Neuroscience and medical instruction]. AB - The historical origins and developments of neuroscience are shortly revised. The recent advances at the molecular level and its relevance for clinical practice are emphasized. The general content of the programs and methods of neuroscience teaching in medicine are briefly discussed. It is concluded that neuroscience education in medicine must be expanded and reorganized in this country both at undergraduate and postgraduate level. PMID- 8209706 TI - [Intrahepatic cholestasis in pregnancy. Its etiopathogenesis, prognosis and therapy]. AB - Intrahepatic cholestasis of pregnancy (ICP) is a rare disease of unknown cause, recurrent, characterized by pruritus and, in some cases, mild jaundice. This cholestasis usually appears during the second half of pregnancy, and resolves in the early puerperium. ICP results in the elevation of serum total bile acids concentrations, mainly cholic acid, and abnormal routine liver function tests. Although maternal outcome is invariably good, an increased fetal risk has been reported, namely premature deliveries, fetal distress, and perinatal mortality. To avoid these deleterious consequences, strict fetal monitoring must be carried out during the final weeks of pregnancy, and the decision for delivery taken as soon as term or fetal maturity are achieved. The ursodeoxycholic acid (UDCA), that has been beneficial in other cholestatic liver diseases therapeutics, may become a promising drug in the treatment of ICP; nevertheless, due to the scarce experience with its use during ICP, and because its metabolism and mechanism of action is still poorly understood, it seems reasonable to test the effect of UDCA in these patients. PMID- 8209708 TI - [Analysis of the evaluation of demand for care in a mental health center]. AB - This study is a descriptive analysis of the evolution of a Community Mental Health Service attendance request. Three significant periods in the history of this centre are selected: its creation, a consolidation stage and, finally another period in which the Mental Health Service constitution has been unified, this period coincides with the Neuropsychiatry figure disappearance. Socio demographics and clinic diagnostic variables are analyzed so the authors can elaborate the characteristic user profile in the periods studied. PMID- 8209709 TI - [Usefulness of computerized tomography in psychiatry]. AB - Since the middle 1970s, C.T. is used to study possible cerebral morphological anomalies in psychiatric patients. In Schizophrenics: most of the studies found enlargement of ventricular volume or increase of the ventricle: brain ratio (VBR). The prevalence varied from 6 to 28% according to 2 or 1 standard deviation respectively. Some clinical researchers detected the anomaly at the first patient's admission or in young non-chronic patients. For this reason they suggest that may be a neuro-developmental process before the onset of symptoms. Others observed the same findings, in chronic patients, with out change over the time. Some authors reported more ventricular and temporal horn volume in male patients. The left temporal horn enlargement correlated with positive and negative symptoms while the right side correlated with attention impairment. The frontal horn (due to anomalies of the zone around) correlated with negative symptoms and poor treatment outcome. The third ventricle was wider in schizophrenics with persistent hallucinations and flat affect. The superficial frontal sulci and Silvian fissure were more dilated; positive psychopathology correlated with left fissure volume and negative symptoms with the right. In affective disorders: Bipolar patients had larger ventricles. Patients suffering major depression had greater cortical atrophy, neuropsychological slowness and radio-density increase of both head caudates and basal ganglia. In obsessive compulsive disorder there was decrease of the caudate nucleus volume. Psychiatrists T.C. petition studies are discussed. TC indications in psychiatry are summarized. PMID- 8209710 TI - [New perspectives on depression]. AB - Traditionally depression was considered as an episodic pathology; however, at present it is seen as a longitudinal disorder that can progress, in most of the cases, in a episodic way throughout the patient life and, in a minor percentage of patients, in a chronic way. The new longitudinal vision has changed the antidepressant treatment guidelines. The duration of the treatment of an episode has been set up in a minimum of six months. When the risk of new episodes is high, prophylactic treatment should be considered in order to keep an euthymic mood. PMID- 8209711 TI - [Endogenous and neurotic depression again, II: is the separation of the two a methodologic artifact?]. AB - The authors study the Kiloh and Garside's (1963) and Carney's et al. (1965) data. They apply a Factorial Analysis without and with Varimax rotation. Only account a bipolar factor (endogenous/neurotic) the unrotated solutions, but not in rotated solutions. They discuss the validity of the classification endogenous/neurotic depression supported by a erroneus application of the Factorial Analysis method. PMID- 8209712 TI - [Social behavior schedule: reliability and validity as an instrument for evaluating chronic mental patients]. PMID- 8209713 TI - [Study of a sample of alcoholic patients two years post-treatment]. AB - This survey analyzes the evolution of one sample of alcoholic patients two years after finishing treatment. Its target is to determine the percentage of patients that remain abstinent, their rate of retention, and what factors can have an influence on abstinence. In 1990, 72 alcoholic patients were treated in the Alcoholism Unit, who make up our study sample. The average age was 37.9 +/- 11.47 years old; 77.8% were diagnosed as being Alcohol-dependents and 22.2% as Alcohol abusers; 19.4% dropped out the treatment early. In 1992 our sample of study was 53 patients (2 died and 17 refused to participate), of whom 77.7% were abstinent and 28.3% continued ingesting alcohol; the average abstinence was 22.92 +/- 8.73 months. An important finding of this study was that the diagnosis, sex, and treatment with aversives had not an influence on abstinence; however the percentage of abstinent patients in those who had attended Therapeutic Discussion Groups was significantly higher than in those who had not. PMID- 8209714 TI - An intraleader open reading frame is selected from a hypervariable 5' terminus during persistent infection by the bovine coronavirus. PMID- 8209715 TI - Genomic organization and expression of the 3' end of the canine and feline enteric coronaviruses. AB - The genomic organization at the 3' end of canine coronavirus (CCV) and feline enteric coronavirus (FECV) was determined by sequence analysis and compared to that of feline infectious peritonitis virus (FIPV) and transmissible gastroenteritis virus (TGEV) of swine. Comparison of the latter two has previously revealed an extra open reading frame (ORF) at the 3' end of the FIPV genome, lacking in TGEV, now designated ORF 6b. Both CCV and FECV possess 6b related ORFs. The CCV ORF 6b is colinear with that of FIPV, but the predicted amino acid sequences are only 58% identical. The FECV ORF 6b contains a large deletion compared to that of FIPV, reducing the colinear part to 60%. The sequence homologies were highest between CCV and TGEV on the one hand and between FECV and FIPV on the other. The expression product of the CCV and the FECV ORF 6b can be detected in infected cells by immunoprecipitation. PMID- 8209716 TI - Effects of mouse hepatitis virus infection on host cell metabolism. AB - A time dependent decrease in cell surface expression of major histocompatibility complex (MHC) class 1 proteins was found during JHMV infection of the mouse macrophage J774.1 cells line by radioimmunoassay. MHC class I, actin and CSF-1 receptor mRNA levels were also found to decrease during infection. Surprisingly, not all host cell mRNA were similarly affected, suggesting that the apparent MHV induced translational shut off of host cell protein synthesis during infection was specific for only some host cell mRNAs. Interestingly, two mRNAs found to be refractory to JHMV infection encode monokines, suggesting a role in pathogenesis. To understand the mechanism(s) of this preferential mRNA stability and the apparent shut off of host cell mRNA, translation lysates were prepared from infected and uninfected cells. Translation of host mRNAs in these extracts showed no apparent loss of translational ability in the infected cells vs. the uninfected cells; however, viral mRNAs were preferentially translated in the lysates from the infected cells. Chimeric mRNAs containing the MHV leader upstream of a globin reporter gene showed that preferential translation was a property of the MHV leader RNA. Deletional analysis showed that the sequences responsible for this cis translational augmentation are in a 12 nucleotide (nt) tract at the 3' end of the leader. The previously reported interaction of the nucleocapsid protein with these nts suggest that it may play a role in translational augmentation of MHV mRNAs. PMID- 8209717 TI - The effect of amantadine on mouse hepatitis virus replication. PMID- 8209718 TI - Analysis of messenger RNA within virions of IBV. AB - The presence of subgenomic mRNAs (sgRNAs) in virions of infectious bronchitis virus was examined by probing Northern blots of RNA extracted from virions using as a probe a cDNA of the 3'-terminal nucleocapsid protein (N) gene. The sgRNAs were readily detected even after extensive purification of virions and after RNase A treatment of virions. The molar ratio of gRNA to each sgRNA was in the range 25 to 400 for IBV-M41 and 10 to 30 for IBV-Beaudette. After comparison with the molar ratios of genomic to intracellular viral sgRNAs it was estimated that the efficiency of incorporation of gRNA into virions was approximately 100 to 500 fold greater than for sgRNAs in the case of M41 and 20 to 100-fold for Beaudette, depending on the sgRNA species. It is concluded that sgRNAs can be present within IBV virions. Approximately 1 in 3 Beaudette virions and 1 in 20 M41 particles might contain a single copy of one sgRNA. PMID- 8209719 TI - Inhibition of mouse hepatitis virus multiplication by antisense oligonucleotide, antisense RNA, sense RNA and ribozyme. AB - Antisense nucleic acids against specific sequences of mouse hepatitis virus (MHV) RNAs were tested for their inhibitory effects on viral multiplication in mouse DBT cells. An antisense oligonucleotide containing a sequence complementary to leader RNA was synthesized and shown to induce a significant inhibitory effect on the multiplication of MHV-JHM. A vector which expressed the antisense or sense mRNA7 of MHV was transfected into DBT cells. A decreased multiplication of MHV was observed in both cell lines. The transfected cell line which expressed ribozyme against the 5'-end of the MHV genome was established. The rate of inhibition of MHV-multiplication and the quantity of synthesized virus-specific mRNAs in this transfected cell line were the same for both antisense and sense RNA. These results show that antisense nucleic acids might be eligible for use as antiviral agents against MHV multiplication. PMID- 8209720 TI - Site-specific sequence repair of coronavirus defective interfering RNA by RNA recombination and edited RNA. PMID- 8209721 TI - Site-directed mutagenesis of the genome of mouse hepatitis virus by targeted RNA recombination. AB - We have genetically characterized a nucleocapsid (N) protein mutant of the coronavirus mouse hepatitis virus (MHV). This mutant, designated Alb4, is both temperature-sensitive and thermolabile, and its N protein is smaller than wild type N. Sequence analysis of the Alb4 N gene revealed that it contains an internal deletion of 87 nucleotides, producing an in-frame deletion of 29 amino acids. All of these properties of Alb4 made it ideal for use as a recipient in a targeted RNA recombination experiment in which the deletion in Alb4 was repaired by recombination with synthetic RNA7, the smallest MHV subgenomic mRNA. Progeny from a cotransfection of Alb4 genomic RNA and synthetic RNA7 were selected for thermal stability. PCR analysis of candidate recombinants showed that they had regained the material that is deleted in the Alb4 mutant. They also had acquired a five nucleotide insertion in the 3' untranslated region, which had been incorporated into the synthetic RNA7 as a molecular tag. The presence of the tag was directly verified, as well, by sequencing the genomic RNA of purified recombinant viruses. This provided a clear genetic proof that the Alb4 phenotype was due to the observed deletion in the N gene. In addition, these results demonstrated that it is possible to obtain stable, independently replicating progeny from recombination between coronaviral genomic RNA and a tailored, synthetic RNA species. To date, we have constructed three additional mutants by this procedure. For two of these, a second-site point mutation that reverts the Alb4 phenotype has been transduced into a wild type background, which does not contain the Alb4 deletion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209722 TI - Homologous RNA recombination allows efficient introduction of site-specific mutations into the genome of coronavirus MHV-A59 via synthetic co-replicating RNAs. AB - We describe a novel strategy to site-specifically mutagenize the genome of an RNA virus by exploiting homologous RNA recombination between synthetic defective interfering (DI) RNA and the viral RNA. Marker mutations introduced in the DI RNA were replaced by the wild-type residues during replication. More importantly, however, these genetic markers were introduced into the viral genome: even in the absence of positive selection MHV recombinants could be isolated. This finding provides new prospects for the study of coronavirus replication using recombinant DNA techniques. As a first application, we describe the rescue of the temperature sensitive mutant MHV Albany-4 using DI-directed mutagenesis. Possibilities and limitations of this strategy are discussed. PMID- 8209723 TI - Identification of peplomer cleavage site mutations arising during persistence of MHV-A59. AB - Primary mouse glial cell cultures were infected with mouse hepatitis virus strain A59 (MHV-A59) and maintained over an 18 week period. Viruses isolated from these cultures 16-18 weeks postinfection produce small plaques on fibroblasts and cause only minimal levels of cell-to-cell fusion at times when wild type causes nearly complete cell fusion. However, when mutant-infected cultures were examined 24-36 hours postinfection approximately 90% of the cells were in syncytia showing that the fusion defect is not absolute but rather delayed. Addition of trypsin to mutant-infected cultures enhanced cell fusion a small (2- to 5-fold) but significant degree. Sequencing of portions of the spike genes of six fusion defective mutants revealed that all contained the same single nucleotide mutation resulting in a substitution of aspartic acid for histidine in the spike cleavage signal. Mutant virions contained only the 180 kDa form of spike protein suggesting that this mutation prevented the normal proteolytic cleavage of the 180 kDa protein into the 90 kDa subunits. Examination of revertants of the mutants supports this hypothesis. Replacement of the negatively-charged aspartic acid with either the wild type histidine or a non-polar amino acid was associated with the restoration of spike protein cleavage and cell fusion. PMID- 8209724 TI - Proteolytic cleavage of the murine coronavirus surface glycoprotein is not required for its fusion activity. AB - The surface glycoprotein (S) of the murine hepatitis coronavirus MHV normally undergoes proteolytic cleavage during transport to the cell surface. To determine whether the cleavage of the MHV-JHM S glycoprotein is required to activate its ability to fuse cellular membranes, the protease recognition sequence in a cDNA copy of the S gene was altered from Arg-Arg-Ala-Arg-Arg into Ser-Val-Ser-Gly-Gly by site directed mutagenesis. The mutated and wild type S genes were expressed by means of recombinant vaccinia viruses and it could be shown that the mutated S protein was not cleaved when it was expressed in mouse DBT cells, in contrast to the wild type S protein. Nevertheless, the non-cleaved S protein induced extensive syncytium formation in mouse DBT cells. These results clearly indicate that the non-cleaved form of the MHV S protein is able to mediate cell membrane fusion. Thus, proteolytic cleavage is not an absolute requirement for its fusion function. PMID- 8209725 TI - Cloning and sequence analysis of the spike gene from several feline coronaviruses. AB - The DNA sequence encoding the spike gene from the DF2 strain of Type II feline infectious peritonitis virus (FIPV), a temperature sensitive FIPV virus (TS-DF2) and an isolate of feline enteric coronavirus (FECV 1683) were determined. Comparison of the published WSU 1146 and DF2 FIPV S genes showed that the viruses shared a high degree of homology (99.6%). Likewise, the S gene of the virulent DF2 FIPV virus was closely conserved to that isolated from the vaccine virus strain, TS-DF2 FIPV. In contrast, the FECV S gene had numerous DNA and amino acid differences when compared to the virulent FIPV sequences. Sequence differences among the feline coronavirus isolates were localized to the amino-terminus region of the S gene. PMID- 8209726 TI - Fusogenic properties of uncleaved spike protein of murine coronavirus JHMV. AB - We have tested the fusogenic properties of cleaved and uncleaved spike (S) protein of murine coronavirus (MCV) JHMV variant cl-2 by expressing the S protein by recombinant vaccinia viruses (RVVs). The amino acid sequence of the putative cleavage site of cl-2 S protein, Arg-Arg-Ala-Arg-Arg, was replaced by Arg-Thr-Ala Leu-Glu by in vitro mutagenesis of cl-2 S gene. The RVVs having cl-2 S gene [RVV t(+)] or mutated cl-2 S gene [RVV t(-)] were tested for their ability to induce fusion as well as cleavability in DBT cells. After inoculation with RVV t(+) onto DBT cells, the fusion formation was first observed at 8 h postinoculation (p.i.) and spread throughout the whole culture by 24 h. In cells infected with RVV t(-), fusion appeared by 2 h and most of cells were fused by 30 h p.i. The S protein and its cleavage products were detected in DBT cells expressing wild type S protein. However, no cleavage products of the S protein were detected in RVV t(-) infected cells producing mutated S protein, even though fusion was clearly visible. These results suggest that the cleavage event of JHMV-S protein of MCV is not a prerequisite for fusion formation, but that it enhances fusion. PMID- 8209727 TI - Characterization of a monoclonal antibody resistant variant of MHV. AB - A monoclonal antibody resistant (MAR) variant of MHV was isolated after infection of hybridoma cells secreting the neutralizing and fusion-inhibiting monoclonal antibody, mAb 11F. The isolated variant was able to mediate syncytia formation even in the presence of high concentrations of mAb 11F. The S gene of the variant was cloned and sequenced. There were three nucleotide exchanges in comparison to the wild-type S gene, resulting in two amino acid alterations. However, both amino acid substitutions (at positions 255 and 1116) were located outside the binding site of mAb 11F. PMID- 8209728 TI - Molecular mimicry between S peplomer proteins of coronaviruses (MHV, BCV, TGEV and IBV) and Fc receptor. AB - In previous studies we have demonstrated molecular mimicry between the S peplomer protein of Mouse Hepatitis Virus (MHV) and Fc gamma Receptor (Fc gamma R) of IgG. Rabbit IgG, but not its F(ab')2 fragments, monoclonal rat and mouse IgG and the rat 2.4G2 anti-mouse Fc gamma R monoclonal antibody (mab) immunoprecipitated natural and recombinant MHV S protein. On the basis of a number of criteria, MHV S peplomer protein exhibits Fc IgG binding ability. We report here a molecular mimicry between the S peplomer protein of Bovine Coronavirus (BCV) and Fc gamma R. BCV S peplomer protein which belongs to the same antigenic subgroup as MHV also binds Fc portion of rabbit IgG and is immunoprecipitated by the 2.4G2 anti Fc gamma R mab. In contrast, Transmissible Gastroenteritis Coronavirus (TGEV) and Infectious Bronchitis Virus (IBV) S peplomer proteins which represent two distinct antigenic subgroups of Coronaviridae do not bind rabbit IgG and do not react with anti-Fc gamma R mab. However, homologous swine IgG, but not its F(ab')2 fragments, immunoprecipitated from TGEV-infected cells a polypeptide chain with molecular mass of 195 kDa, identical to that immunoprecipitated by the T36 mab anti-TGEV S peplomer protein. PMID- 8209729 TI - Complex formation between the spike protein and the membrane protein during mouse hepatitis virus assembly. AB - Using different approaches we have demonstrated the formation of a complex between the S protein and the M protein in the process of mouse hepatitis virus (MHV) assembly. Preservation of the M/S heterocomplexes was critically dependent on the solubilization conditions. Pulse-chase labeling of MHV-infected cells followed by a co-immunoprecipitation assay revealed that newly synthesized S and M engage in complex formation with different kinetics, the S protein reacting much slower. Sedimentation experiments showed the M/S heteromultimer complexes to be very large. A model for the role of the complex formation in MHV assembly is presented. PMID- 8209730 TI - Preliminary characterization of a monoclonal antibody specific for a viral 27 kD glycoprotein family synthesized in porcine epidemic diarrhoea virus infected cells. AB - We describe a new monoclonal antibody No. 204 (mcAb 204) which recognized a family of four polypeptides, consisting of a 27kD, a 24/23kD double band and a 19kD protein present within PEDV infected cell lysates. These proteins were identified by immunoprecipitation as well as by staining of immunoblots. In infected Vero cell cultures, the synthesis of the 27kD protein was initiated between 6 and 8 hours post inoculation. The 24/23kD double band and the 19kD protein were only detectable later. At least the 27 and the 24/23kD proteins were apparently glycosylated and present in purified virions. Pulse-chase as well as solubilization experiments indicated that the faster migrating bands represented processed products of the 27kD glycoprotein. The nature of the processing is not known at present. We suggest that the 27kD protein family may represent the integral membrane protein M of PEDV. Since this protein is highly abundant in virions as well as in infected cells, and since mcAb 204 is able to react with its antigen under various conditions, this monoclonal antibody may be useful to further studies of the M-protein of PEDV. In addition, it may provide a useful tool for routine diagnosis. PMID- 8209731 TI - Involvement of lipids in membrane binding of mouse hepatitis virus nucleocapsid protein. AB - Evidence is presented which indicates that membrane binding of the MHV nucleocapsid (N) protein is influenced by membrane lipid composition. Binding of N protein to membranes of mouse fibroblast L-2 cells is very specific and occurs under conditions in which no other viral or cellular proteins show detectable binding. Binding occurs rapidly and does not require the presence of divalent cations such as Ca++ or Mg++. Purified phospholipid liposomes compete against N protein binding to membranes. Phospholipids consisting of cardiolipin are the most effective in inhibiting membrane binding. Because of certain structural similarities between phospholipids and nucleic acids, we speculate that membrane lipid association of the N protein may compete for RNA binding sites on the N protein. Such a mechanism may be important for processes such as nucleocapsid uncoating and nucleocapsid assembly. PMID- 8209732 TI - A novel glycoprotein of feline infectious peritonitis coronavirus contains a KDEL like endoplasmic reticulum retention signal. AB - A new protein of the feline infectious peritonitis virus (FIPV) was discovered in lysates of infected cells. Expression of the gene encoding open reading frame (ORF) 6b of FIPV in recombinant vaccinia virus infected cells was used to identify it as the 6b protein. It is a novel type of viral glycoprotein whose function is not clear. It is a soluble protein contained in microsomes; its slow export from the cell is caused by the presence of an ER-retention signal at the C terminus. This amino acid sequence, KTEL, closely resembles the consensus KDEL signal of soluble resident ER proteins. A mutant 6b protein with the C-terminal sequence KTEV became resistant to digestion by endo-beta-N-acetylglucosaminidase H with a half-time that was reduced threefold. In contrast, a mutant with the sequence KDEL was completely retained in the ER. The FIPV 6b protein is the first example of a viral protein with a functional KDEL-like ER-retention signal. PMID- 8209734 TI - A newly identified MHV-A59 ORF1a polypeptide p65 is temperature sensitive in two RNA negative mutants. AB - Polypeptide products of MHV-A59 gene 1 have been identified in infected DBT cells and in the products of in vitro translations of genome RNA. In this paper we report the identification in infected cell lysates of a 65-kDa polypeptide (p65) encoded in ORF 1a. Studies on the kinetics of appearance and processing of p65 show that p65 is detectable after p28 but before the appearance of p290, p240 and p50. No homologue of the p65 polypeptide identified in infected cell lysates was immunoprecipitated from in vitro translations of genomic RNA, providing further evidence that in vitro processing of polypeptides encoded in ORF 1a of gene 1 differs from that which occurs late in infection of DBT cells. Although the function of p65 is unknown, two MHV-A59 ts mutants isolated and characterized by Baric et al. (3,4) do not produce detectable levels of p65 at the non-permissive temperature indicating that p65 may play an important role in the virus life cycle. PMID- 8209733 TI - Altered proteolytic processing of the polymerase polyprotein in RNA(-) temperature sensitive mutants of murine coronavirus. AB - We examined the synthesis and processing of the polymerase polyprotein in RNA(-) temperature sensitive mutant of murine coronavirus strain A59. These temperature sensitive mutants of MHV-A59 synthesize viral RNA at the permissive temperature (33.0 degrees C), but are unable to synthesize viral RNA at the nonpermissive temperature (39.5 degrees C). The ts mutants have been mapped to five different complementation groups in the polymerase gene. The 5'-most complementation groups, Groups A and B, map to a region encoding an autoproteinase responsible for the cleavage of p28, the amino-terminal product of the polymerase polyprotein. We screened six temperature sensitive mutants to determine if there was an alteration in the proteolytic processing of the polymerase polyprotein, particularly in the cleavage of the p28 protein. Two mutants, tsNC9 and tsLA16, had altered proteolytic products at both the permissive and nonpermissive temperatures. One Group B temperature sensitive mutant, designated tsNC11, was defective in the production of p28 protein at the nonpermissive temperature. To further localize the site of the mutation in tsNC11, RNA representing the 5'-most 5.3 kb region of the polymerase gene was transfected into tsNC11-infected cells and virus production monitored. The transfected RNA was able to complement the defect in tsNC11, resulting in viral RNA synthesis and production of viral particles at the nonpermissive temperature. These results indicate that a gene product from the 5.3 kb region of gene 1 is required for coronavirus RNA synthesis. PMID- 8209735 TI - Proteolytic processing of the N-terminal region of the equine arteritis virus replicase. AB - A papainlike cysteine protease (PCP) domain in the N-terminal region of the equine arteritis virus (EAV) replicase was identified by in vitro translation and mutagenesis studies. The EAV protease was found to direct an autoproteolytic cleavage at its C-terminus which leads to the production of an approximately 30K N-terminal replicase product (nsp1) containing the PCP domain. Amino acid residues Cys164 and His230 of the EAV replicase polyprotein were identified as the most likely candidates for the role of PCP catalytic residues. It was shown that cleavage occurs in cis between Gly260 and Gly261. PMID- 8209736 TI - Genomic organisation of a virulent Taiwanese strain of transmissible gastroenteritis virus. AB - Transmissible gastroenteritis (TGE) infection causes 65% of infectious piglet diarrhoea in Taiwan. A virulent Taiwanese strain, TFI, of transmissible gastroenteritis virus (TGEV) from a field outbreak was isolated in cell culture and plaque purified. Phenotypic differences were observed in the ability of TFI to infect certain cell lines. TGEV strains TLM-83 (PRCV Belgium), TO-163 (TGEV Japan) and Purdue-115 (TGEV USA) infected both ST (swine testis) and RPTG (pig kidney) cell lines whereas TFI infected ST but not RPTG cells. To investigate this phenotypic variation cDNA was generated from TFI genomic and amplified by PCR with oligonucleotides derived from published TGEV sequence data. An 8.4kb cDNA derived from the 3'-end of the TFI genome was sequenced. Eight ORFs, corresponding to the three structural protein genes, four potential genes and the 3'-end of an incomplete ORF whose amino acid sequence corresponded to the carboxyl end of the 1b subunit of the polymerase gene, were identified on the TFI sequence. The overall sequence similarity of TFI with the other TGEV strains was over 97%. However, several deletions, insertions and point mutations were found on the TFI sequence when compared with other TGEV strains. The TFI S protein was found to contain 1449 amino acids, as also identified for the FS772/70 and Miller TGEV strains, but two amino acids longer than the Purdue S protein. The TFI ORF 3a gene encodes 72 amino acids, however, a 37 nucleotide deletion was found 16 nucleotides downstream of the TFI ORF-3a stop codon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209737 TI - The coronaviruslike superfamily. PMID- 8209738 TI - Equine arteritis virus contains a unique set of four structural proteins. PMID- 8209739 TI - The Coronaviridae now comprises two genera, coronavirus and torovirus: report of the Coronaviridae Study Group. AB - At the April 1992, mid-term meeting of the International Committee on Taxonomy of Viruses (ICTV) a proposal from the Coronaviridae Study Group (CSG) to include the torovirus genus in the Coronaviridae was accepted. Following another proposal, the arterivirus genus was removed from the Togaviridae but not assigned to another family. The arteriviruses have some features in common with the Coronaviridae but also have major differences. After much debate, culminating in September 1992, it was decided that the CSG would not recommend inclusion of arterivirus in the Coronaviridae. It was agreed that (a) the nomenclature used for coronavirus genes, mRNAs and polypeptides (Cavanagh et al., 1990) should be used for toroviruses, (b) that the small (about 100 amino acids) membrane associated protein, which is distinct from the integral membrane glycoprotein M, associated with virions of infectious bronchitis (Liu & Inglis, 1991) and transmissible gastroenteritis (Godet et al., 1992) coronaviruses would be referred to by the acronym sM (lower case 's') and (c) that 'pol' (polymerase) should be used as a working term for gene 1, which comprises open reading frames (ORFs) 1a and 1b in both genera of the Coronaviridae. PMID- 8209740 TI - Coronavirus receptor specificity. PMID- 8209741 TI - Expression of MHV-A59 receptor glycoproteins in susceptible and resistant strains of mice. PMID- 8209742 TI - Mouse hepatitis virus infection utilizes more than one receptor and requires an additional cellular factor. PMID- 8209743 TI - Dissemination of MHV4 (strain JHM) infection does not require specific coronavirus receptors. AB - In this report, we demonstrate the syncytial spread of MHV4 (strain JHM) infection through non-murine cell cultures which lack a specific MHV4 receptor and are therefore resistant to infection by free virions. This was achieved by allowing infected murine cells to settle onto confluent monolayers of non-murine cells in a straightforward infectious center assay. Receptor-independent syncytium formation induced by cells expressing the MHV4 spike (S) from recombinant vaccinia viruses (VV) indicated that spread was mediated by this coronavirus glycoprotein. We conclude that the S protein of MHV4 is so potently fusogenic that it does not require prior binding to a virus-specific surface receptor to induce fusion of closely-opposed plasma membranes. PMID- 8209744 TI - Virus-ligand interactions of OC43 coronavirus with cell membranes. AB - The binding of human coronavirus OC43 to human rhabdomyosarcoma cells which are highly susceptible to infection was studied by a solid phase virus binding assay and a receptor blockade assay. It was observed that whole virions and S(spike) bound to a 90 kD glycoprotein of RD cells even after treatment of the substrate with neuraminidase or 0.1 M NaOH. A second receptor of 45 kD also bound virus and was identified as HLA class I antigen. Antibody to both receptors reduced the virus yield in a receptor blockade assay. Sera from four patients with multiple sclerosis contained receptor blocking activity which correlated with antibodies to HLA. No receptor blocking antibodies to the 90 kD RD cell protein were found in human sera. PMID- 8209745 TI - The use of PCR genome mapping for the characterisation of TGEV strains. AB - Previous studies on different transmissible gastroenteritis virus (TGEV) strains, including porcine respiratory coronavirus (PRCV), have identified regions within the genome that are polymorphic as regards insertions and deletions. For example the 672 base deletion within the S gene and multiple deletions 5', within and 3' of the ORF-3a gene were detected in strains of PRCV. The presence of deletions may be associated with a change in the virulence, attenuation or tissue tropism of the isolate. The Nouzilly (188-SG) TGEV vaccine strain was attenuated by passage of a cell culture adapted virulent isolate D-52 188 times through swine testis cells after treatment with gastric juice. PCR amplification with oligonucleotides, corresponding to known TGEV sequences, were used to analyse D 52 and 188-SG for genetic variation. Results with several pairs of oligonucleotides within the first 1565 nucleotides of the S gene did not identify a deletion within this region of the genome from either strain. However, oligonucleotides directed against the ORF-3a/3b region detected a deletion of about 250 nucleotides within the 188-SG genome but not in the D-52 genome. Since all the attenuated TGEV strains so far sequenced, PRCV, Miller SP and 188-SG, contained deletions within the ORF-3a/3b, it would suggest that this region of the TGEV genome is involved in regulating viral virulence. PMID- 8209746 TI - Recognition of N-acetyl-9-O-acetylneuraminic acid by bovine coronavirus and hemagglutinating encephalomyelitis virus. AB - The S protein of hemagglutinating encephalomyelitis virus is shown to be a hemagglutinin requiring N-acetyl-9-O-acetylneuraminic acid as a receptor determinant on the surface of erythrocytes. The ability of bovine coronavirus to recognize 9-O-acetylated sialic acid was used to establish a binding assay for the detection of glycoproteins containing this type of sugar. The assay is very fast, because it uses the acetylesterase of the viral HE protein to localize bound virus. PMID- 8209747 TI - Sequence analysis of CCV and its relationship to FIPV, TGEV and PRCV. PMID- 8209748 TI - N-acetylneuraminic acid plays a critical role for the haemagglutinating activity of avian infectious bronchitis virus and porcine transmissible gastroenteritis virus. AB - Porcine transmissible gastroenteritis virus (TGEV) was found to resemble avian infectious bronchitis virus (IBV) in its interaction with erythrocytes. Inactivation of the receptors on erythrocytes by neuraminidase treatment and restoration of receptors by reattaching N-acetylneuraminic acid (Neu5Ac) to cell surface components indicated that alpha 2,3-linked Neu5Ac serves as a receptor determinant for TGEV as has been reported recently for IBV. Similar to IBV, the haemagglutinating activity of TGEV is evident only after pretreatment of virus with neuraminidase indicating that inhibitors on the virion surface have to be inactivated in order to induce the HA-activity of these viruses. A model is presented to explain why the HA-activity of untreated virus is masked and how neuraminidase treatment results in the unmasking of this activity. PMID- 8209749 TI - MHV-JHM infections of rodent neuronal cells: replication and trafficking of structural proteins and progeny virions. PMID- 8209750 TI - The route of transmission of hemagglutinating encephalomyelitis virus (HEV) 67N strain in 4-week-old rats. AB - Four-week-old Wistar rats were inoculated with HEV by different routes. Animals died of encephalitis after intraperitoneal (i.p.), subcutaneous (s.c.) and intravenous (i.v.) as well as intracerebral (i.c.) and intranasal (i.n.) inoculation. However when inoculated subcutaneously, rats died a few days earlier than those inoculated i.p. and i.v., suggesting that the virus might be transmitted to the central nervous system (CNS) by the neuronal route rather than by blood stream. Rats which were inoculated subcutaneously at the site of the neck (group A) began to die on day 4 p.i., a few days earlier than animals inoculated in the foot pad of the right leg (group B). On day 2 and 3 after inoculation, the virus titer in the brain was higher in group A, but group B animals showed higher virus titers in the lumber region of spinal cord than group A animals. In order to follow the virus spread from the peripheral nerve to the brain, the virus was inoculated into the sciatic nerve of rats. The inoculated rats developed clinical signs on day 4 and began to die on day 6. On day 2, virus was detected in the posterior half of the spinal cord and migrated toward the anterior half and in the brain where it was present on day 3. The highest virus titers in the brain were recorded on day 4 to 6, meanwhile the virus titers in the spinal cord tend to decrease. By immunohistochemical study, antigen positive neurons were found in the spinal cord and brain on day 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209751 TI - Neurotropism of human coronavirus 229E. AB - The 299E prototype strain of human coronavirus (HCV-229E) has so far been mainly associated with infections of the respiratory tract. In the present study, we show evidence for infection of the central nervous system (CNS) by HCV-229E, both in vitro and in vivo. Various human cell lines of CNS origin were tested for their susceptibility to infection by HCV-229E. Production of viral antigens was monitored by indirect immunofluorescence with monoclonal antibodies and infectious progeny virions by plaque assay on the L132 human embryonic lung cell line. The SK-N-SH neuroblastoma and H4 neuroglioma cell lines were highly susceptible to infection. The U-87 MG and U-373 MG astrocytoma cell lines were also infectable by HCV-229E. We could also demonstrate infection of the MO3.13 cell line, which was established by fusion of human oligodendrocytes with a thioguanine-resistant mutant of the TE671 (RD) human rhabdomyosarcoma cell line. An apparently more extensive infection of the MO3.13 cells, when compared to the parental cells, supports the notion that human oligodendrocytes are differentially susceptible to infection by this virus. We also tested for HCV 229E gene expression in pathological brain specimens. For that purpose, we developed a reverse transcription-polymerase chain reaction (RT-PCR) assay to amplify a portion of the mRNA encoding the viral nucleocapsid protein. Using stringent laboratory conditions, viral RNA was detectable in brain tissue of 4 of 11 multiple sclerosis patients and none of 6 neurological and 5 normal controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209752 TI - Coronavirus JHM OMP1 pathogenesis in owl monkey CNS and coronavirus infection of owl monkey CNS via peripheral routes. AB - Two separate studies are described in this report. First, 5 Owl monkeys were inoculated intracerebrally (IC) with coronavirus JHM OMP1; this virus isolate was cultured from the brain of an animal inoculated with uncloned MHV JHM. Two of the animals became neurological impaired and were sacrificed; these animals had developed severe encephalomyelitis as previously described. Two of the remaining 3 healthy animals were inoculated IC again at 90 days post-inoculation (DPI) and all 3 were sacrificed approximately 5 months after the first virus inoculation. Despite the lack of detectable infectious virus, viral RNA and antigen, all 3 animals had significant white matter inflammation and areas of demyelination in the spinal cord. In the second study 4 Owl monkeys were inoculated intranasally (IN) and ocularly and 4 inoculated intravenously (i.v.) with JHM OMP1. The animals were sacrificed between 16 and 215 DPI with 2 IN and 2 i.v. animals receiving a second i.v. inoculum at 152 DPI. Viral RNA and/or antigen was detected in the brains of all animals and the distribution corresponded to areas of inflammation and edema. One of the animals that received the second inoculum developed neurological impairment and subsequent analysis of tissues showed viral antigen in both brain and spinal cord. Viral products were predominantly found in blood vessels suggesting hematogenous spread with entry into the central nervous system (CNS) through endothelium. PMID- 8209753 TI - Evolution and tropism of transmissible gastroenteritis coronavirus. AB - Transmissible gastroenteritis coronavirus (TGEV) is an enteropathogenic coronavirus isolated for the first time in 1946. Nonenteropathogenic porcine respiratory coronaviruses (PRCVs) have been derived from TGEV. The genetic relationship among six European PRCVs and five coronaviruses of the TGEV antigenic cluster has been determined based on their RNA sequences. The S proteins of six European PRCVs have an identical deletion of 224 amino acids starting at position 21. The deleted area includes the antigenic sites C and B of TGEV S glycoprotein. Interestingly, two viruses (NEB72 and TOY56) with respiratory tropism have the S protein with a similar size to the enteric viruses. NEB72 and TOY56 viruses have 2 and 15 specific amino acid differences with the enteric viruses, respectively. Four of the residues changed are located within the deletion present in the PRCVs and may influence the enteric tropism of TGEV in vivo. A receptor binding site (RBS) used by the virus to infect ST and other cell types might be located between sites A and D of the S glycoprotein, since monoclonal antibodies (MAbs) specific for these sites inhibit the binding of the virus to ST cells. An evolutionary tree relating 13 enteric and respiratory isolates has been proposed. According to this tree, a main virus lineage evolved from a recent progenitor which was circulating around 1941. From this, secondary lineages originated PUR46, NEB72, TOY56, MIL65, BRI70, and the PRCVs, in this order. Least squares estimation of the origin of TGEV-related coronaviruses showed a significant constancy in the mutation fixation rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209754 TI - Coronaviruses and multiple sclerosis. PMID- 8209755 TI - Electrocardiographic changes following rabbit coronavirus-induced myocarditis and dilated cardiomyopathy. AB - Rabbit Coronavirus (RbCV) infection was divided into two phases based upon day of death and pathologic findings. During the acute phase (days 2-5) heart weights (HW) and heart weight-to-body weight (HW/BW) ratios were increased with striking dilation of the right ventricle. These changes as well as increased dilation of the left ventricle were especially pronounced during the subacute phase (days 6 12). Myocytolysis, pulmonary edema, and degeneration and necrosis of myocytes, were seen during both phases. Myocarditis, pleural effusion, calcification of myocytes, and congestion in the liver and lungs were seen in the subacute phase. Electrocardiograms (ECGs) exhibited low voltage, nonspecific ST-T wave changes, sinus tachycardia, occasional ventricular and supraventricular premature complexes and 2(0) AV block consistent with myocarditis and heart failure. Forty one percent of the survivors exhibited increased HW and HW/BW ratios, biventricular dilation, interstitial and replacement fibrosis, myocyte hypertrophy and myocarditis. ECGs exhibited nonspecific ST-T wave changes, sinus arrhythmia, occasional ventricular and supraventricular premature complexes and 2(0) AV block. These data suggest that RbCV infection may result in viral myocarditis and heart failure with a proportion of survivors progressing into DCM. PMID- 8209756 TI - Role of host age and genotype in murine enterotropic coronavirus infection. PMID- 8209757 TI - Role of macrophage procoagulant activity in mouse hepatitis virus (MHV) infection: studies using T cell MHV-3 clones and monoclonal antibody 3D4.3. PMID- 8209758 TI - Early cellular events in the induction of murine hepatitis virus (MHV-3) induced macrophage procoagulant activity (PCA). PMID- 8209759 TI - Corona viruses from persistent infected cell cultures and brain tissue: molecular analysis of the S gene of an a virulent variant. PMID- 8209760 TI - Characterization of IBV variant strain PL 84084 isolated in France. PMID- 8209761 TI - Recombinant vaccinia viruses which express MHV-JHM proteins: protective immune response and the influence of vaccination on coronavirus-induced encephalomyelitis. AB - Vaccinia-virus (VV) recombinants encoding either the nucleocapsid (N) or the spike (S) protein of MHV-JHM were constructed to study the role of the immune response against defined coronavirus antigens. For the S-protein, a fusogenic (Sfus+) or non fusogenic variant (Sfus-) of the gene was inserted into the VV genome. A strong protection against acute encephalomyelitis (AE) was mediated in Lewis rats which were immunized by VV-Sfus+ and challenged with an otherwise lethal dose of MHV-JHM before the induction of S-specific IgG antibodies. By contrast, a VV recombinant encoding a variant non fusogenic S-protein or the N protein was not capable conferring protection. In addition, we demonstrated that MHV-JHM S-specific IgG antibodies elicited before MHV-JHM challenge modulated the disease process, changing it from an acute disease to subacute demyelinating encephalomyelitis (SDE). PMID- 8209762 TI - JHM virus-specific cytotoxic T cells derived from the central nervous system. AB - Spleen cells cultured from Balb/c mice immunized with the JHM strain of mouse hepatitis virus (JHMV) have CD8+ cytotoxic T cells (CTL) specific for both the S and N proteins, but not the M or HE proteins. T cell lines were established from the brains of Balb/c mice infected with JHMV. The majority of the lines (20 of 22) were specific for JHMV. Analysis of the viral structural proteins which served as target structures indicate that most (15 of 20) were specific for the N protein. One line was specific for the S protein and four lines were specific for JHMV but the protein recognized could not be determined. These data suggest that early during infection there is a preferential recruitment of N protein specific CTL into the CNS of infected mice. PMID- 8209763 TI - On the role of different lymphocyte subpopulations in the course of coronavirus MHV IV (JHM)-induced encephalitis in Lewis rats. PMID- 8209764 TI - Transmissible gastroenteritis virus and porcine respiratory coronavirus: molecular characterization of the S gene using cDNA probes and nucleotide sequence analysis. AB - Two transmissible gastroenteritis virus (TGEV, Miller strain) cDNA clones were identified and their nucleotide sequences determined. The clones were non overlapping and were located in the 5' region of the S glycoprotein gene. The TGEV clone pE21 contained 381 bp of the S glycoprotein gene and had > 98% nucleotide and amino acid sequence homology with the Purdue (P115) strain of TGEV and over 87% sequence homology with feline infectious peritonitis virus (FIPV). The TGEV clone, pD24, contained 267 bp of the S glycoprotein gene. It had > 98% nucleotide and amino acid sequence homology with P115 but only a 49% nucleotide sequence homology and a 24% amino acid sequence homology with FIPV. Using dot blot hybridization, a probe prepared from pD24 could differentiate TGEV from the antigenically related coronaviruses, FIPV, feline enteric coronavirus and canine coronavirus. This probe could also differentiate TGEV from porcine respiratory coronavirus (PRCV). Using polymerase chain reaction amplified regions of PRCV isolates and nucleotide sequencing, a 681 bp deletion in the 5' region of the S gene from PRCV isolate ISU-1 was identified. This deletion was located in the area of the S glycoprotein gene identified by the pD24 probe. PMID- 8209765 TI - Functional characterization of CD8+ lymphocytes during coronavirus MHV IV induced encephalitides in rats. PMID- 8209766 TI - Cytokine induction in vitro in mouse brain endothelial cells and astrocytes by exposure to mouse hepatitis virus (MHV-4, JHM). PMID- 8209767 TI - Structural proteins of avian infectious bronchitis virus: role in immunity and protection. AB - The antigenicity of the S1, M and N proteins of avian infectious bronchitis virus was compared following immunization of chickens with live and inactivated virus. The N protein was immunodominant antigen inducing cross-reactive antibodies in high titres whereas the S1 glycoprotein induced serotype-specific and cross reactive antibodies. The M glycoprotein elicited antibodies in low titres and of limited cross-reactivity. Immunization of chickens with the purified N and M proteins did not induce protection against virulent challenge whereas immunization with the S1 glycoprotein prevented replication of nephropathogenic IBV in kidneys but not in tracheas of immunized chickens. PMID- 8209768 TI - An overview of successful TGEV vaccination strategies and discussion on the interrelationship between TGEV and PRCV. AB - Porcine respiratory coronavirus (PRCV) is a new variant of TGE with an altered pathogenesis. PRCV multiplies mainly in tonsilar tissues and the respiratory tract. There are no enteric symptoms and in experimentally infected pigs, even the respiratory tract infection is usually asymptomatic. PRCV is spread aerogenically through herds and the significance of PRCV as a pathogen in swine has yet to be determined. Despite the differences in pathogenesis and tissue tropism, the behavior of TGEV and PRCV are closely related antigenically. PRCV induces an antibody response in pigs that cannot be distinguished from TGEV infected pigs by conventional serological assays. PRCV sensitized animals are not protected from TGEV challenge nor is the milk antibody provided to nursing piglets completely effective in prevention of TGEV infections; thus PRCV is not a good vaccine candidate for TGEV infections. PRCV subclinical infections have led to several reported cases of enzootic TGEV in herds that had been diagnosed as TGEV immune strictly on the basis of serum neutralizing titers which were later found to be due to exposure to PRCV. Vaccination studies conducted with the Ambico, oral modified live TGEV vaccine have led to some startling new results: (1) Use of Ambico TGEV modified live vaccine has been shown to provide complete protection against subsequent PRCV challenge and (2) the effectiveness of TGEV vaccination is actually enhanced by previous exposure to PRCV (3) Weanling pigs which have passively acquired circulating TGEV neutralizing antibodies are protected from subsequent PRCV infections. PMID- 8209769 TI - Construction of a recombinant adenovirus for the expression of the glycoprotein S antigen of porcine respiratory coronavirus. PMID- 8209770 TI - Sequence analysis of the nucleocapsid protein gene of porcine epidemic diarrhoea virus. AB - The nucleotide (nt) sequence of 1.7 kbp cDNA representing the 3' end of the PEDV genome has been determined. Viral RNA was reverse transcribed and the cDNA was amplified by polymerase chain reaction using degenerate primers. The sequences of the primers were based on conserved regions of coronaviral genomes. A 1323 nt open reading frame (ORF) showed good homology to the nucleocapsid (N) gene of other coronaviruses. The greatest homologies at the amino acid and the nt levels were observed with Human Coronavirus 229E. A second 336 nt ORF, which might encode a leucine-rich protein, was found within the N gene. Between the 3' end of the N gene and the poly(A) tail was a sequence of eleven nt, which is conserved among the other sequenced coronaviruses. Finally, a seven base sequence similar to the conserved intergenic sequences was present 5' to the N gene. These results confirm the classification of PEDV as a coronavirus. PMID- 8209771 TI - Genome organization of porcine epidemic diarrhoea virus. AB - In order to study the organization of the genome of porcine epidemic diarrhoea virus (PEDV), we constructed a cDNA library in a phage expression vector by using poly(A) RNA from PEDV-infected Vero cells. An anti-PEDV hyperimmune serum was used to probe the library. The first isolated clone mapped within the N gene and was subsequently used for rescreening the library. The selected clones allowed us to establish the sequence of the 3'-most 7.4 kb of the PEDV genome. Analysis of the cDNA sequences revealed a 3'-coterminal nested structure, which is typical of Coronaviridae and the presence of a hexameric sequence XUA(A/G)AC upstream of each coding region. The amino acid sequences deduced from four of the five ORFs identified showed the characteristic features of the structural proteins S, M, sM and N. Only one ORF located between the S and M genes was found to potentially encode a non-structural polypeptide. Our data lead us to conclude that PEDV is a member of Coronaviridae and belongs to the same genetic subset as TGEV, FIPV and HCV 229E. PMID- 8209772 TI - Characterization of the nonstructural and spike proteins of the human respiratory coronavirus OC43: comparison with bovine enteric coronavirus. AB - The nucleotide sequence of the region between the spike (S) and the membrane (M) protein genes, and sequences of the S and ns2 genes of the OC43 strain of human coronavirus (HCV-OC43) were determined. The ns2 gene comprises an open reading frame (ORF) encoding a putative nonstructural (ns) protein of 279 amino acids with a predicted molecular mass of 32-kDa. The S gene comprises an ORF encoding a protein of 1353 amino acid residues, with a predicted molecular weight of 149,918. Sequence comparison between HCV-OC43 and the antigenically related bovine coronavirus (BCV) revealed more sequence divergence in the putative bulbous part of the S protein (S1) than in the stem region (S2). The cysteine residues near the transmembrane domain and the internal predicted protease cleavage site are conserved in the HCV-OC43 S protein. Nucleotide sequence analysis of the region between the S and M gene loci revealed the presence of an unexpected intragenomic partial leader sequence and two ORFs encoding potential proteins of 12.9 and 9.5-kDa. These two proteins were identified as nonstructural by comparison with the homologous BCV genes. In vitro translation analyses demonstrated that the HCV-OC43 9.5-kDa protein, like its BCV counterpart, is poorly translated when situated down-stream of the 12.9-kDa ORF, but is expressed in infected cells, as shown by immunofluorescence. Interestingly, two ORFs, potentially encoding 4.9 and 4.8-kDa ns proteins in BCV are absent in HCV-OC43, indicating that they are not essential for viral replication in HRT-18 cells. PMID- 8209773 TI - Identification, expression in E. coli and insect cells of the non-structural protein NS2 encoded by mRNA2 of bovine coronavirus (BCV). AB - The coding part of mRNA 2 (ORF2) of BCV (F15 strain) was cloned and sequenced. The comparison of our sequence data with the sequence of the same ORF of BCV Quebec strain previously published revealed a major difference in the length of the C-terminal part of the NS2 protein. In vitro transcription and translation of ORF2 resulted in the synthesis of a single protein migrating with a Mr of 31 kDa. The ORF2 was fused in frame with the glutathione S transferase gene (GSH) in the pGEX vector. The fusion protein was synthesized as inclusion bodies which were concentrated and used to raise a monospecific antiserum. Alternatively the fusion protein was solubilized, purified by affinity chromatography and cleaved with Factor Xa to yield pure recombinant NS2. The ORF2 was also expressed in the baculovirus system and the recombinant proteins expressed in pro- and eukaryotic systems were compared on the basis of their size and immunoreactivity. Immunoprecipitation performed with the monospecific antiserum allowed us to identify NS2 in HRT18 infected cells, to follow its kinetic of synthesis, and to ascertain that NS2 was not incorporated in the virion as a minor structural component. PMID- 8209774 TI - Characterization of the human coronavirus 229E (HCV 229E) gene 1. AB - The sequence of the HCV 229E gene 1 has been determined and compared with the homologous sequences of the murine hepatitis virus and the avian infectious bronchitis virus. The coding sequence of gene 1 is 20,273 nucleotides in length. Within this coding region are two large open reading frames, ORF 1a (4,086 codons) and ORF 1b (2,687 codons) which overlap by 40 nucleotides. In the overlapping region, the genomic RNA can be folded into a pseudoknot structure, an element which is known to mediate -1 ribosomal frame-shifting in other coronaviruses. Assuming that -1 frame-shifting occurs at the HCV sequence UUUAAAC (nucleotides 12,514-12,520), the ORF 1a - ORF 1b product is predicted to be 6,758 amino acids in length. Our sequence analysis of the HCV 229E gene 1 has revealed a high degree of similarity within the ORF 1b of HCV, MHV and IBV, whereas ORF 1a is much less conserved. Elements which are believed to be necessary for specific (e.g. frame-shifting) and general (e.g. NTP-binding/helicase) transcriptional functions have been identified. This study completes the genomic sequence of HCV 229E which is 27.27 kb long and one of the largest known RNA genomes. PMID- 8209775 TI - Identification of coronaviral conserved sequences and application to viral genome amplification. PMID- 8209776 TI - Studies into the mechanism for MHV transcription. AB - Previous studies have demonstrated that the MHV genome is divided into seven transcriptional units which are transcribed from highly conserved intergenic start sites (UCU/CAAAC) into mRNA containing a common leader RNA at the 5' end and a coterminal 3' end. In this manuscript, we provide evidence that an additional transcriptional unit is encoded at the 3' end of the MHV genome and is transcribed from a perfect intergenic region into a leader-containing approximately 800 nt mRNA. This mRNA could potentially encode a small 17-18 kDa protein which is identical to the C-terminal third of the nucleocapsid gene. PMID- 8209777 TI - Analysis of the cis-acting elements of coronavirus transcription. PMID- 8209778 TI - Control of TGEV mRNA transcription. AB - Coronavirus proteins are translated from a nested set of subgenomic mRNAs which have common 3' termini with unique 5' extensions. Evidence suggests that coronavirus mRNAs are generated by a mechanism of leader primed transcription. Leader RNA binds to consensus sequences upstream of each gene on full length negative strand viral RNA and transcription proceeds to the 5' end of the negative strand to produce the nested set of mRNAs. Even though this gives rise to polycistronic mRNA species only the 5' extension of each mRNA is translated to give the viral proteins. The leader RNA for TGEV is about 90 nucleotides long and contains the sequence which recognises the leader binding sites on the negative strand RNA. Evidence suggests that the length of the leader binding sequence may be involved in transcriptional control of individual mRNAs. In order to investigate this a virus specific mRNA isolation method was developed to measure the relative amounts of mRNAs synthesised during an infection of LLC-PK1 cells with TGEV (strain FS772/70). Thus the relative quantity of each mRNA can be determined and correlated with the variation in size of the leader binding site. PMID- 8209779 TI - The platelet as a Ca(2+)-driven cell: mechanisms which may modulate Ca(2+)-driven responses. PMID- 8209780 TI - The use of inhibitors of protein kinases and protein phosphatases to investigate the role of protein phosphorylation in platelet activation. PMID- 8209781 TI - Serine/threonine kinases in signal transduction in response to thrombin in human platelets. Use of 17-hydroxywortmannin to discriminate signals. AB - Although the importance of protein kinases in platelet activation, particularly protein kinase C (PKC), is well established there remain many problems regarding the various phosphorylation cascades, the role of phosphatases and the importance of other serine/threonine and tyrosine kinases. A particular problem is the mechanism of activation of the fibrinogen receptor, GPIIb/IIIa, a critical step in aggregation. Although GPIIIa is phosphorylated (on threonine) neither the stoichiometry nor the minor changes on activation seem adequate to explain the response. Relatively unspecific inhibitors of PKC such as staurosporine prevent PO4 incorporation into most kinase substrates but only inhibit platelet aggregation partially. However, staurosporine does induce activation and then inhibits several renaturable serine/threonine kinases, probably via phosphatases. Staurosporine did not, however, inhibit the platelet Ca2+ signal in response to thrombin but rather enhanced it. 17-Hydroxywortmannin (HWT), a fungal metabolite, has been shown to inhibit respiratory burst in neutrophils and causes haemorrhages. It was recently reported to be a myosin light chain kinase (MLCK) inhibitor and to inhibit PKC only at much higher concentrations. In platelets, HWT inhibits aggregation and partially inhibits phosphorylation of myosin light chain and P47 in thrombin-activated platelets. It also allows the discrimination of an early and a late phase in the cytoplasmic Ca2+ signal since at lower concentrations it only inhibits the late phase. The late phase of ATP release was also inhibited in a dose-dependent manner. The activation of most of the renaturable serine/threonine kinases was also inhibited by HWT. These results support earlier conclusions that the early phase of the Ca2+ signal is phospholipase C dependent but indicate that other mechanisms must be responsible for the late phase. The relative specificity of HWT for MLCK might indicate that this has an unexpected major role in controlling these late phase reactions including activation of GPIIb/IIIa or its clustering. However, staurosporine completely inhibits phosphorylation of myosin light chain by its kinase (as well as other kinases) and has the opposite effect on Ca2+ signals. Clearly, the interactions and feed-back mechanisms between these kinases are very complex but the results suggest that phosphatases acting together with their complementary kinases should also be considered as important platelet activation regulators. P47, long considered a major PKC substrate, may also be phosphorylated by MLCK. PMID- 8209782 TI - Tyrosine phosphorylation in platelets: its regulation and possible roles in platelet functions. PMID- 8209784 TI - Inositol lipid metabolism, the cytoskeleton, glycoprotein IIb IIIa and platelets. PMID- 8209783 TI - Evidence that activation of phospholipase D can mediate secretion from permeabilized platelets. AB - Studies on electropermeabilized human platelets indicated that any two of three distinct factors must be present for marked secretion of dense or alpha-granule constituents to occur. These factors are Ca2+, activation of protein kinase C (PKC) and activation of an unidentified GTP-binding protein ('GE'). Thus, in the absence of Ca2+, phorbol ester and GTP[S] acted synergistically to promote secretion, whereas in the presence of Ca2+, either activation of PKC or addition of GTP[S] was sufficient. In all cases, secretion correlated with the activation of phospholipase D (PLD), as detected by the formation of [3H]phosphatidic acid (PA) in the absence of ethanol or of [3H]phosphatidylethanol (PEt) in the presence of ethanol. Secretion did not correlate with phospholipase C (PLC) activity or with the accumulation of 1,2-diacylglycerol (DAG), both of which required Ca2+ and were inhibited by phorbol ester. Ethanol partially inhibited secretion in the absence of Ca2+. BAPTA, a known inhibitor of Ca(2+)-independent secretion in permeabilized cells, caused parallel inhibitions of secretion and PLD activity. GTP[S] enhanced PKC activity, as indicated by pleckstrin phosphorylation, apparently by stimulating the formation of PA in the absence of Ca2+, as well as of DAG in the presence of Ca2+. PA and stable analogues, including PEt, stimulated the Ca(2+)-independent phosphorylation of pleckstrin and other proteins in platelet supernatant fraction. The results suggest that PA formed by activation of PLD may mediate secretion from permeabilized platelets by PKC-dependent and independent mechanisms. However, in intact platelets stimulated by thrombin, PLD accounted for only 10-20% of the total PA formed and can only play a major role in secretion if this PA fraction is distinct from that formed by the combined actions of PLC and DAG kinase. PMID- 8209785 TI - Agonist receptors and G proteins as mediators of platelet activation. AB - Recent studies have helped to define the earliest events of signal transduction in platelets, particularly those involved in the generation of second messengers. The best-understood of these events are those which involve guanine nucleotide binding regulatory proteins. G proteins are heterotrimers comprised of alpha, beta and gamma subunits, each of which can exist in multiple forms. Some, but not all, of the known variants of G alpha are substrates for ADP-ribosylation by pertussis toxin, a modification which disrupts the flow of information from receptor to effector. The G proteins that have been identified in platelets to date are Gs, Gi1, Gi2, Gi3, Gz and Gq. Gs and one or more of the Gi family members regulate cAMP formation by adenylylcyclase. Gi may also be responsible for the pertussis toxin-sensitive activation of phospholipase C which occurs when platelets are activated by thrombin. Gq is thought to be responsible for the pertussis toxin-resistant activation of phospholipase C by TxA2. Gz does not have an established role, but has the unique property of being phosphorylated by protein kinase C during platelet activation. Recent efforts to clone the receptors that interact with G proteins in platelets have been successful for epinephrine, thrombin, TxA2 and platelet activating factor. Each of these resembles other G protein-coupled receptors, being comprised of a single polypeptide with 7 transmembrane domains. In the case of thrombin, receptor activation is thought to involve a unique mechanism in which thrombin cleaves its receptor, creating a new N-terminus that can serve as a tethered ligand. Peptides corresponding to the tethered ligand can mimic the effects of thrombin, while antibodies to the same domain inhibit platelet activation. Shortly after activation, thrombin receptors become resistant to re-activation by thrombin. This desensitization, which appears to be due to a combination of proteolysis, phosphorylation and internalization, provides a potential mechanism for limiting the duration of thrombin-initiated signals in platelets. PMID- 8209786 TI - Regulation of platelet function by the cytoskeleton. AB - The platelet cytoskeleton contains two actin filament-based components. One is the cytoplasmic actin filaments that fill the cytoplasm and mediate contractile events. The other is the membrane skeleton that coats the plasma membrane and regulates properties of the membrane such as its contours and stability and the lateral distribution of membrane glycoproteins. Recent work reviewed in this article indicates that the GP IIb-IIIa complex can associate with the membrane skeleton. Upon platelet activation, GP IIb-IIIa becomes competent to bind its adhesive ligand, fibrinogen. This induces a reorganization of the cytoskeleton such that the membrane skeletal proteins with which GP IIb-IIIa is associated become associated with underlying cytoplasmic filaments. As in focal contacts of cultured cells, this ligand-induced association of GP IIb-IIIa with cytoplasmic actin filaments regulates the ability of GP IIb-IIIa to bind adhesive ligand. Intracellular enzymes that are activated as a consequence of ligand binding to the GP IIb-IIIa complex include tyrosine kinase(s) and calpain, making these potential candidates for enzymes inducing the two-way signaling across the membrane. Additional candidates include phosphoinositide 3-kinase and protein kinase C, other enzymes that have been detected in focal contacts of aggregating platelets. Future studies identifying interactions between the GP IIb-IIIa complex and membrane skeletal proteins should help to further elucidate the significance of the GP IIb-IIIa in cytoskeleton interaction in regulating integrin-mediated transmembrane signaling in platelets. PMID- 8209787 TI - Cytoskeletal interactions of Rap1b in platelets. AB - We have presented evidence that rap1b, a 22 kDa low molecular weight GTP binding protein, becomes associated with the cytoskeleton in thrombin-activated platelets. The initial incorporation is very rapid and occurs as fast as we can measure it. Thus, some rap1b is associated with the cytoskeleton as fast as it is formed. The remainder of the rap1b is incorporated more slowly. This biphasic incorporation of rap1b is similar to the incorporation of GPIIb/IIIa into the cytoskeleton, but no interaction between GPIIb/IIIa and rap1b could be demonstrated. Phosphorylation of rap1b by cAMP-dependent protein kinase did not inhibit its association with the cytoskeleton. We conclude that rap1b is one of an increasing number of proteins that associate with the cytoskeleton during cell activation. The function of rap1b in the cytoskeleton is unclear at this time. However, it is possible to speculate on potential roles. There is growing evidence that low molecular weight G proteins participate in the formation of multi-molecular aggregates. For example, p21rac promotes the assembly of a membrane-associated complex composed of NADPH oxidase, p47, and p67 and this complex is important for activation of NADPH oxidase in neutrophils. Similarly, in yeast, BUD1, a homolog of rap1, forms a complex with BUD5 (a homolog of GDI), BEMI, CDC24, and CDC42 (a homolog of G25K). This multi-protein aggregate may be important in cytoskeletal structure in yeast. In platelets, rad1b, which is membrane associated, may promote the assembly of a complex of proteins during cell activation and may localize this complex to the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209788 TI - Mechanisms involved in platelet procoagulant response. PMID- 8209789 TI - Histamine as an intracellular messenger in human platelets. AB - The results of investigations in platelets provide evidence for an intracellular messenger role for histamine. Studies of neutrophils and of cellular proliferation suggest that there may be a wider role for histamine as an intracellular messenger modulating activation processes in cells. PMID- 8209790 TI - Platelet activation via binding of monoclonal antibodies to the Fc gamma receptor II. PMID- 8209791 TI - Role of cyclic nucleotide-dependent protein kinases and their common substrate VASP in the regulation of human platelets. AB - The activation of human platelets is inhibited by two intracellular pathways regulated by either cGMP- or cAMP-elevating agents. There is considerable evidence that the inhibitory effects of cGMP and cAMP are mediated by the cGMP-PK and cAMP-PK, respectively, in human platelets. The cGI-PDE is an additional target for cGMP, and the cGMP-mediated elevation of cAMP levels contributes to the well known synergism between cAMP- and cGMP-elevating platelet inhibitors. Stimulation of both cAMP-PK and cGMP-PK prevents the agonist-induced activation of MLCK and PKC and inhibits the agonist-induced calcium mobilization from intracellular stores without any major effect on the ADP-regulated cation channel. These studies suggest that the inhibition of an early event of platelet activation, e.g. activation of PLC, is an effect common to both cGMP-PK and cAMP PK stimulation. A common substrate of both cGMP-PK and cAMP-PK, the 46/50 kDa protein VASP, has been recently identified as a novel microfilament- and focal contact-associated protein whose phosphorylation correlates very well with platelet inhibition. Future investigations will have to identify the precise molecular mechanism of cyclic nucleotide inhibition of Ca2+ discharge from intracellular stores and whether cGMP-PK- and cAMP-PK-mediated VASP phosphorylation is an important component of this effect of cyclic nucleotides in human platelets. PMID- 8209792 TI - Regulation of phosphoinositide-specific phospholipase C activity in human platelets. PMID- 8209793 TI - Calcium signalling and phosphoinositide metabolism in platelets: subsecond events revealed by quenched-flow techniques. PMID- 8209794 TI - Calcium influx mechanisms and signal organisation in human platelets. PMID- 8209795 TI - Ca2+ homeostasis and intracellular pools in human platelets. PMID- 8209796 TI - Measures of susceptibility from a spiral gradient of drug concentrations. PMID- 8209797 TI - Commercialization of nucleic acid probe technology: current status. PMID- 8209798 TI - Is one laboratory in town enough? PMID- 8209799 TI - The FDA review criteria for assessment of antimicrobial susceptibility devices- too much or not enough regulation? PMID- 8209800 TI - The evolution of clinical laboratory regulation--a primer for universal health care. PMID- 8209801 TI - Antimicrobial susceptibility tests: testing methods and interpretive problems. PMID- 8209802 TI - Current issues in antimicrobial susceptibility testing. PMID- 8209803 TI - The use of in-vitro kinetic models in the evaluation of beta-lactam/beta lactamase inhibitor combinations. PMID- 8209804 TI - Prevalence of ticarcillin/clavulanic acid-resistant Enterobacteriaceae in nine separate medical centers during the years 1983, 1989, and 1991. PMID- 8209805 TI - Correlation of minimum inhibitory concentration results between the Vitek system and the BIOMIC system. PMID- 8209806 TI - Clinician utilization of rapid antibiotic susceptibility data: a prospective study. PMID- 8209807 TI - The evolution of antimicrobial susceptibility testing methods. PMID- 8209808 TI - When we should be testing, how often and what to report. PMID- 8209809 TI - Areas of recent emphasis of the National Committee for Clinical Laboratory Standards Subcommittee on Antimicrobial Susceptibility Testing. PMID- 8209810 TI - Non-traditional approaches for quality control of antimicrobial susceptibility tests. PMID- 8209811 TI - Applications of medical informatics in antibiotic therapy. AB - The Infectious Disease Society of America is concerned about the excessive and inappropriate use of antibiotics in U.S. hospitals. Applications of Medical Informatics can help improve the use of antibiotics and help improve patient care by monitoring and managing enormous amounts of patient information. Monitoring the duration of every antibiotic ordered in the hospital or keeping tract of the antibiotic susceptibilities for five years are examples of tasks better performed by computers. The impact of computers in medicine is seen by some as disappointing. The computer revolution has not had the impact in medicine experienced by other areas. The acceptance and use of computers by medicine will be evolutionary rather than revolutionary. In 1979, the MYCIN project demonstrated that the computer could aid physicians in the selection of antibiotics. However, MYCIN was never clinically used because physicians were require to enter all patient information into the computer. The development of computerized medical records is an essential step to further the development and implementation of computer-aided decision support. The science of Medical Informatics is still relatively new but is emerging as a distinct academic field. A few hospitals are now installing information systems and have determined that these systems will play an essential role in their ability to survive into the next century. The telephone and the automobile have been recognized as two of the most important tools for improving medical care during the past 100 years. People could more readily get medical care and the time to transmit medical information was greatly reduced through physician use of the telephone and automobile. The computer is a tool that can be used to help physicians manage the great amount of medical information being generated every day. The computer can also alert the physician of patient conditions that need attention. However, it is the physician who must use and apply the computer provided information. Thus, the computer will assist but not replace physicians in providing medical care. PMID- 8209812 TI - Established antimicrobial susceptibility testing methods with a new twist--points to consider and a glimpse of the future. AB - The developments seen in these systems allow speculation about future trends in antimicrobial susceptibility testing methods. Microbiology system manufacturers seem to be heeding the call of all industry, for greater automation, enhanced data management capabilities and increased flexibility (see Table 2 below). [table: see text] Cost seems to be less of an issue. This may be due to the decrease in the availability of medical technologists and the need to find systems with better throughput and increased productivity. Increased automation, data management capabilities, and walkaway technology may justify the additional cost of some of these systems. The computer software package provided with these systems is becoming increasingly important with the focus on quality assurance and utilization. Computer generated data analysis gives the microbiologist the tools to educate physicians through the use of selective reporting functions, antibiograms, cost analysis and drug effectiveness comparisons. Each of the four systems is unique and will probably find a niche among the various markets that exist in the United States, European and other specialized markets. The lack of automation in the ALAMAR system may be its selling point in those areas where automation is not affordable, but new ways are being sought for ease of interpretation of results. BIOMIC and CATHRA systems may be more beneficial to those microbiologists who do not want to stop doing traditional Bauer-Kirby or agar dilution methods, but require computer enhancements. ALADIN, may fill a niche to which other walkaway systems have not adapted, but because of its expense, will face more demands than the other three systems covered in this review. PMID- 8209813 TI - Purification and characterization of IgM-like immunoglobulin from turbot (Scophthalmus maximus L.). AB - A total of 40 turbot (Scophthalmus maximus) were immunized 3 times during a 3 months period using DNP-HSA whereafter serum samples were collected and pooled. Specific immunoglobulins (Ig) were affinity purified on an agarose column with immobilized DNP-BSA and further purified by gel filtration whereafter monospecific rabbit anti Ig serum was generated. Size exclusion chromatography and non-reduced SDS-PAGE indicated a MW of 8-900 kDa of the dominant antigen binding proteins from turbot serum. Reduced SDS-PAGE showed this fraction to be composed of disulphide linked heavy and light chains with MWs of 79 and 27-29 kDa, respectively, indicating a tetrameric structure. Isoelectric focusing of the 800-900 kDa Ig showed several bands between pH 5.5 and pH 5.8. Mean Ig concentration in serum of 10 turbot was measured to 6.48 mg/ml (SD 5.4) using rocket immunoelectrophoresis. Low molecular weight antigen binding molecules were copurified with the dominating immunoglobulins with an estimated MW of 500 kDa. Reducing SDS-PAGE of this fraction revealed molecules with MWs of 97, 79, 57, 29, and 27 kDa. PMID- 8209814 TI - Cerebellar abiotrophy in a moose (Alces alces L) related to copper deficiency. A case report. PMID- 8209815 TI - Local tissue damage in cows after intramuscular injections of eight antimicrobial agents. PMID- 8209816 TI - Occurrence of Listeria species in an abattoir for cattle and pigs in Bosnia and Hercegovina. AB - Altogether 496 samples of meat, lymph nodes, process water and swabs from different places in the abattoir were examined for the presence of Listeria spp. L. monocytogenes was isolated from 31 (6%) and other Listeria spp. from 65 (13%) samples L. monocytogenes was isolated from 2 of 10 beef meat samples, 4 of 50 pig meat samples and 1 of 21 lymph nodes of pigs. No Listeria bacteria were isolated from lymph nodes of cattle. The highest percentage of Listeria was recovered from the unclean sections (cattle 22% and pigs 27%) and the highest frequency was observed during the winter months. PMID- 8209817 TI - Portal infusion of low dosage endotoxin: a model simulating translocation of ruminal endotoxin in cattle. PMID- 8209818 TI - Membrane alterations in bull spermatozoa after freezing and thawing and after in vitro fertilization. AB - Membrane alterations in bull spermatozoa after freezing and thawing and after the process of in vitro capacitation and fertilization were studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Even if the majority of the spermatozoa exhibited intact membranes after freezing and thawing (90%), one could distinguish between 3 types of membrane defects depending of the different structures involved. The first type showed loss of plasmalemma over the entire acrosome. In the second category the anterior part of the outer acrosomal membrane exhibited a pronounced extension, but was covered by a partly intact plasmalemma. The last category consisted of spermatozoa with extensive vesiculation and disruption of plasmalemma and the outer acrosomal membrane. This type of defect could not easily be distinguished from a true acrosome reaction. The cumulus cells showed an active phagocytosis of both intact and acrosome reacted spermatozoa. PMID- 8209819 TI - Biochemical phenotypes of Salmonella Livingstone isolated from humans, animals and feedstuffs in Sweden. AB - Salmonella Livingstone is occasionally isolated from humans, animals and feedstuffs in Sweden. To follow the spread of infection and trace the source of isolates, adequate typing methods are needed. We have developed an automated typing system based on biochemical fingerprinting of bacteria (the PhP system) for typing of different Salmonella serotypes. The system measures the kinetics of various biochemical reactions of bacteria grown in liquid medium in microtiter plates and uses numerical techniques to identify biochemical phenotypes (BPTs) among the tested strains. In the present study we used a set of 16 highly discriminatory tests to differentiate strains of Salmonella of serotype Livingstone and evaluated the system for its discriminatory ability using a collection of 34 unrelated human isolates of S. Livingstone. We also used the system to investigate BPTs of 45 Livingstone strains isolated from animals and feedstuffs in Sweden between 1987 and 1991. Altogether 19 different BPTs were found among human isolate giving a diversity index (Di) of 0.930. In contrast, most strains isolated from animals and feedstuffs in Sweden belonged to 2 dominating BPTs (Di = 0.704). One of these contained 17 strains mainly isolated during 1992 whereas the other contained 18 strains isolated between 1987 and 1991. None of the Swedish human isolates were identical to those of animals and feedstuffs. These findings suggest that 2 different BPTs of Salmonella Livingstone strains are particularly common among animals and feedstuffs in Sweden and that they are not related to human cases of enteritis in this country. We also conclude that biochemical fingerprinting with the PhP system is a reliable and highly discriminatory method for detecting epidemic strains of Salmonella Livingstone. PMID- 8209820 TI - Rapeseed products from double-low cultivars as feed for dairy cows: effects of long-term feeding on thyroid function, fertility and animal health. AB - Eighty-five dairy cows of the Swedish Red and White Breed (SRB) were included in a long-term experiment during 3 consecutive lactations. The cows were divided into 3 different dietary groups that received no rapeseed (NR), up to 1.2 kg dry matter (DM) 00-rapeseed meal plus 0.2 kg DM full-fat 00-rapeseed (MR), and up to 2.5 kg DM 00-rapeseed meal plus 0.9 kg DM full-fat 00-rapeseed (HR) per day. No significant differences in culling rates or disease rates were found between the feeding groups at any time during the experiment. The interval from calving to conception among the primiparous cows was longer for the HR-group (125 days) than for the NR-group (100 days). The response to a thyrotroph releasing hormone around 90 days postpartum during the first lactation was significantly higher for the HR-group (86.7 mu/L/h) than for the NR-group (55.2 micrograms/L/h). This indicates that at the highest level of rapeseed feeding, glucosinolates had a very mild, suppressive influence on thyroid hormone release, apparently compensated for by an increased activity along the hypothalamic-pituitary-thyroid axis. No significant differences in fertility or thyroid function were found among the pluriparous cows. During 2nd lactation the concentration of serum urea was higher in the NR-group (7.31 mmol/L) than in the HR-group (6.83 mol/L). The effects of independent environmental factors influenced fertility and thyroid function to a much greater extent than the rapeseed feeding. It was concluded that the feeding of rapeseed products from certified double low varieties of B. napus to adult dairy cows in amounts up to 3 kg rapeseed meal per cow and day would not have any negative effects on animal health or fertility. PMID- 8209821 TI - Haemorrhages of the sole horn of dairy cows as a retrospective indicator of laminitis: an epidemiological study. AB - Eleven herds with clinical laminitis problems and 11 control herds were studied for 2 consecutive years. All the claws were trimmed and photographically recorded once each year, 2 to 6 months after the cows had calved. The haemorrhages of the sole horn were evaluated and scored for each digit, and data relevant to the factors associated with an increased risk of laminitis for each herd were collected and related to these scores for sole haemorrhages. It was found that the laminitic herds were more prone to the sole lesions than the control herds, the hind claws were more prone than the front claws, the primiparous cows were more prone than the multiparous cows and the Swedish Friesian cows were more prone than the Swedish Red and White cows. High scores were also correlated with hard floors (ie concrete) in the cow stalls, with fewer than 4 daily feedings of concentrates, with a short time allocated for the cows to eat concentrates, with feeding concentrates only at the first meal in the morning and in the afternoon and with the interaction between these last 2 variables. PMID- 8209822 TI - The diurnal variation of urea in cow's milk and how milk fat content, storage and preservation affects analysis by a flow injection technique. AB - Six Swedish Red and White dairy cows, producing 20-39 kg of 4% fat-corrected milk were given a ration balanced in energy and protein. They had access to feed from 05.15 to 09.00 and from 13.00 to 16.30 and were milked at 06.15 and 15.30. The milk was analysed for urea with a FIA technique. There was a significant diurnal variation in milk urea. The highest values were found 3-5 h after the beginning of the morning feeding and the lowest values (down to 60% of the max. values) during late night. Within 1 h after the start of the morning feeding the urea values had increased significantly, but they had decreased within the same time after the start of the afternoon feeding. Since there was a pronounced diurnal variation in the milk fat content, the urea concentration was also recalculated to concentration in the water phase of the milk. It was higher in that phase, but the pattern of the diurnal variation was not changed significantly. However, analyses on milk with a very high fat content may give misleading results. There were no important differences in the milk urea concentration of different udder quarters. When calculated as concentration in the water phase of the milk, no differences in urea concentration were found between the beginning and the end of milking. The analytical method had a good precision (coefficient of variation max. 3%). The milk urea concentration was not changed significantly after storage during 10 days at 4 degrees C when no preservative was added; but after 17 days the milk had turned sour and the urea value had increased. When a preservative (bronopole) was added the urea concentration remained unchanged during 17 days. Deepfreezing did not influence the urea concentration. PMID- 8209823 TI - Border disease virus transmitted to sheep and cattle by a persistently infected ewe: epidemiology and control. AB - In a Swedish sheep flock comprising 202 ewes and 13 rams, a pair of twin lambs born in the spring of 1990 demonstrated signs of border disease (BD) and were persistently infected (PI) with border disease virus (BDV). Investigation showed that BDV had been introduced in the preceding tupping period 5-6 months earlier by a bought-in ewe which, on the basis of immunoperoxidase- and polymerase chain reaction techniques, was shown to be PI with BDV. Only 7 of the ewes, all of which had been in close contact with the PI ewe, seroconverted during the subsequent gestation. Apart from the PI twin lambs the losses caused by BDV were restricted to 2 barren ewes. The twin lambs, the PI ewe and lambs from the other 4 ewes that seroconverted were removed from the flock. The flock was thereafter free from an ongoing infection with BDV as shown by the absence of seroconversion. In addition, 5 heifers in late pregnancy most probably seroconverted to bovine virus diarrhoea virus (BVDV) when kept in close contact with the same PI ewe during the winter of 1989-90. When these heifers were reintroduced to the BVDV-free dairy herd from which they originated, their serum antibody titres ranged between 1:250 and 1:1250. Neither these heifers--not their calves--caused any spread of the infection in the herd, as indicated by the absence of seroconversion in 70 cows. The present investigation shows that in the control of both BDV in sheep and BVDV in cattle, it is important to ensure that the risk of transmission of pestivirus between the 2 species is minimized. PMID- 8209824 TI - Follicular development and embryo recovery following 3 versus 8 FSH injections in heifers. AB - Ovarian follicular dynamics and embryo yield were studied during 2 different FSH regimens for superovulation of cattle. Twenty heifers were given intramuscular injections of FSH (total of 35 mg NIH) either once daily for 3 days (Group 3x1) or twice daily for 4 days (Group 4x2). At 72 h after the first FSH injection, each animal was injected with 0.75 mg cloprostenol. Inseminations were performed at 12 h and 24 h after the onset of heat. Transrectal ultrasonography was performed on the day of the first FSH injection, the day of cloprostenol injection, the day of insemination and finally on the day of embryo recovery (day 6 or 7 after heat). The numbers of small (2-4 mm), medium (5-9 mm) and large (> 10 mm) size follicles were recorded. The total number of corpora lutea, eggs and transferable embryos were recorded on the day of embryo recovery. No differences were found between the 2 groups in either of the parameters studied (p > 0.05). It can be concluded that treatment with this FSH preparation once daily for 3 days gives a folliculogenic and superovulatory response similar to a treatment regimen where it is given twice daily for 4 days. PMID- 8209825 TI - Mycoplasma hyorhinis in the etiology of serositis among piglets. AB - In a study on the involvement of Mycoplasma hyorhinis in serositis of piglets, 26 routine diagnostic animals, 3-7 weeks old, with distinct serofibrinous lesions in the pericardial, pleural and peritoneal cavities were examined. M. hyorhinis was isolated in 9 cases, non-haemolytic Escherichia coli in another 9 cases and in 4 cases both species were found. Neither of the microorganisms were found in the remaining 4 cases. The presence of M. hyorhinis in the serous cavities in the absence of non-haemolytic E. coli was always accompanied by a diagnosis of other disease conditions, mainly of the respiratory tract. In the cases infected with non-haemolytic E. coli complicating problems were absent. The pathogenicity of M. hyorhinis was further studied by inoculation of 2 young pigs in which the typical serofibrinous lesions of the serous cavities were produced. It therefore appears that M. hyorhinis can be regarded as a cause of polyserositis in piglets; under field conditions, however, the synergistic presence of other debilitating syndromes appears necessary for its haematogenous spread from the respiratory tract to the serous cavities. PMID- 8209826 TI - Liberation of PGF2 alpha from whole blood as an assay to detect inflammatory mediators. PMID- 8209827 TI - Slips and mistakes in dispensing. PMID- 8209828 TI - Pharmacy malpractice: crisis or crucible? PMID- 8209829 TI - Specializing in biotechnology pharmaceuticals. PMID- 8209830 TI - Pharmacists' use of safety caps on refilled prescriptions. AB - Investigations have shown that pharmacists' use of child-resistant containers for dispensing prescriptions has been inconsistent. Use of new child-resistant containers when refilling prescription orders, however, has not been studied. For this study, an investigator presented a prescription order for 30 amitriptyline 50-mg tablets to 50 randomly selected pharmacies in Memphis. Approximately three weeks later, the investigator returned the empty prescription vials to the pharmacies for refills. Of the 44 pharmacies that completed the study, 39 (89%) dispensed the original drug in child-resistant containers, and 38 (86%) dispensed the refill in child-resistant containers. Only 29 (66%) refilled prescriptions were placed in new prescription vials, as specified by federal regulation. Chain pharmacies were twice as likely (p < 0.005) to dispense the refills in new containers as were independent pharmacies. PMID- 8209832 TI - Understanding chronic fatigue syndrome. PMID- 8209831 TI - Family violence and the community pharmacist. PMID- 8209833 TI - Implementing pharmaceutical care: evolution vs. revolution. PMID- 8209834 TI - Defining the lead detection and abatement industry: a review of the AIHA white paper on environmental lead. American Industrial Hygiene Association. PMID- 8209835 TI - Variation in quantitative respirator fit factors due to fluctuations in leak size during fit testing. AB - Variation in fit factors during quantitative respirator fit testing was studied for a high degree of fit (aerosol fit factors > 1000) and a low degree of fit (aerosol fit factors < 1000). In a controlled human study, fit factors were determined sequentially for three different exercises by (1) an aerosol fit test (using a portable condensation nuclei counter and room aerosol as the test agent) and (2) the newly developed dichotomous-flow fit test (Dichot). For the higher level of respirator fit, the aerosol fit factors were 30 to 60 times the corresponding flow fit factors, and for the lower level of respirator fit they were 2 to 4 times the flow fit factors. A coefficient of variation (CV) of 84% (GSD 1.6) for the higher respirator fit and 178% (GSD 2.2) for the lower respirator fit data was observed in the human study when aerosol fit factors for the three exercises were pooled. In a similar mannequin study, the center sampling probe gave aerosol fit factors with a CV of 5.4% (GSD 1.05). The flow fit factors for all three exercises pooled had a CV of 36% (GSD 1.3) for the higher respirator fit and 40% (GSD 1.5) for the lower respirator fit data, while the mannequin study gave flow fit factors with a CV of 2.2% (GSD 1.02). Thus, the variation in fit factors obtained in the human study was much higher than that obtained in a mannequin study. However, the variation in the aerosol method relative to the flow method, in the human study, os of the same order of magnitude as in the mannequin study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209836 TI - Visual field loss while wearing full-face respiratory protection. AB - The loss of visual field was quantified for 21 test subjects while they wore three full-face respirators. Changes in visual field were quantified for each type of respirator using a modified Goldmann projection perimeter. The loss of visual field was determined by calculating the area under the curve while wearing a respirator to that while wearing no respirator. Distinct patterns of visual field loss were apparent for the different style respirators. Analysis of the patterns could lead to the design of full-face respirators with improved visual qualities, which could improve worker safety for certain occupations. This technique also could be of help when selecting models of respiratory protection when certain visual fields must be maintained. PMID- 8209837 TI - Estimated workplace protection factors for positive-pressure self-contained breathing apparatus. AB - An analytical model is presented that estimates the distribution of workplace protection factor (WPF) values for positive-pressure respirators. Input for the model is (1) the instantaneous facepiece pressure measured as a function of time and (2) the distribution of WPF values for a negative-pressure version of the respirator. As an example application, the model was applied to 57 measurements of facepiece pressure made in a previous National Institute for Occupational Safety and Health study called "Firesmoke." That study involved professional firefighters wearing positive-pressure self-contained breathing apparatus (SCBA). During Firesmoke, there were four donnings in which facepiece pressure momentarily went negative one or more times during use. The purpose of the effort described here was to assess the significance of these momentary, negative excursions in facepiece pressure. To that end, an analytical model was developed that estimates the ratio of the mass of contaminant that enters the facepiece during these negative excursions to that which would be expected to enter a negative-pressure respirator utilizing the same facepiece. Thus, the performance of a positive-pressure SCBA can be determined relative to the performance of a negative-pressure respirator with the same facepiece--either a negative-pressure SCBA or a negative pressure air-purifying respirator. The NIOSH-assigned protection factor (APF) for a negative-pressure full facepiece is 50; the APF for a positive-pressure SCBA is 10,000. The results of the application of this analytical model are consistent with the current NIOSH APF for a positive pressure SCBA. PMID- 8209838 TI - Generation of hexahydrophthalic anhydride atmospheres in a controlled human-use test chamber. AB - A method for generating controlled atmospheres of hexahydrophthalic anhydride (HHPA) in an 8 m3 exposure chamber was developed. The permeation principle was used for gaseous HHPA generation. HHPA concentration was monitored by sampling on XAD-2 tubes and by a Fourier-transform infrared (FTIR) spectrometer using the partial least-square quantitative method. The repeatability of the FTIR was 5%, the reproducibility 12%, and the limit of detection 10 micrograms/m3. A bubbler method determined the sum of HHPA and HHP acid by using gas chromatography/mass spectrometry detection after derivatization with methanol/boron trifluoride. The precision of the work-up procedure was 3% and the recovery was 94% at 300 ng sampled amount of HHPA. The limit of detection was 10 ng HHPA. The variation in the permeation rate was 3% over 3 days. Different concentrations in the exposure chamber were generated by changing the temperature of the permeation tubes. The generated HHPA concentration range, at human exposure, was 3-90 micrograms/m3. The concentration at one temperature was reproducible even after major changes in the temperature. The coefficient of variation (CV) of six samples from different places in the breathing zone was 3%. The variation in the concentration, during an 8-hour human exposure at 10 micrograms/m3, was 3%. Time-weighted averages (8 hour) for human exposures of 10 micrograms/m3 (CV = 15%; n = 6); 37 micrograms/m3 (CV = 5%; n = 5); and 81 micrograms/m3 (CV = 6%; n = 9) were obtained at intended concentrations of 10 micrograms/m3, 40 micrograms/m3, and 80 micrograms/m3. The loss of HHPA in the exposure chamber was 54% (CV = 17%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209839 TI - Evaluation of wipe sampling materials for lead in surface dust. AB - The suitability of several commercially available wipe sampling materials for the determination of lead in dust on solid surfaces was evaluated. Criteria for the selection of wipe materials appropriate for field use and subsequent laboratory analysis were identified. These included (a) uniform background lead levels in the materials (preferably < 5 micrograms); (b) ease of digestion in nitric acid/hydrogen peroxide or nitric acid/perchloric acid leachate; (c) > or = 80% recoveries of lead from standard reference material spikes; and (d) ease of use in the field. Other candidate wipe materials that were not examined in this study can be evaluated in a similar manner. PMID- 8209840 TI - Ethanol emission factors for glazing during candy production. AB - This study determined emission rates of ethyl alcohol from a candy glazing operation and, from observation of source activities, expressed these emission rates as emission factors. A mass balance modeling approach was used in conjunction with on-site field testing. The candy was processed in a row of 24 rotating open-faced pans, each with a capacity of approximately 250 lb candy/batch. Twelve 1-hour periods were monitored during production over two days. Ethanol vapor samples were collected on charcoal tubes simultaneously at four locations at different distances from the pan line. Continuous monitoring also was carried out at one location with a gas analyzer. The tube samples were analyzed by gas chromatography. Ventilation measurements and source activity observations were collected at the same time as the gas samples. The average concentration 1.5 m in front of the line was above 1000 ppm. Average emission rates for 12 one-hour periods, determined from the concentration measurements and three different forms of the ethanol mass balance around the space, were 38.4 kg/hour, 42.5 kg/hour, and 49.6 kg/hour. When emission rates were compared with the number of batches the resulting emission factors were 500 g/batch, 291 g/batch, and 453 g/batch, respectively. These values were in good agreement with the estimate of 446 g/batch developed from the glaze mixture composition and the approximate amount of glaze mixture added to each batch. Testing using the emission factor approach removes the effect of the particular interior space in which the data are collected and reproduces changes in emissions and exposures. PMID- 8209841 TI - A comprehensive reproductive health program in the workplace. AB - This paper summarizes the reproductive health component of the AT&T Bell Laboratories occupational health program. The comprehensive R&D Reproductive Health Program is a collaborative effort between the Health Services Group and the Environmental Health & Safety Center. It provides a tailored curriculum to occupational health nurses and physicians so that they may respond to employee questions and concerns with detailed information and with referrals to appropriate subject-matter experts. Expanding on the typical regulatory approaches of hazard communication and right-to-know, the program encourages employees of both sexes to learn about workplace, environmental, and lifestyle aspects of reproductive and developmental health. PMID- 8209842 TI - Electric and magnetic fields at three pulp and paper mills. AB - Extremely low frequency (60 Hz) electric and magnetic field levels were measured at three Canadian pulp and paper mills, using area point-in-time measurements. Most electric field levels were below the limit of detection of 1 V/m (92 of 132 measurements); the highest measured field was 47 V/m. Measured magnetic field strengths ranged from less than the limit of detection (0.125 mG, 2 of 132 measurements) to 706 mG, with a median of 1.6 mG. Magnetic field levels were higher in mills that consume more electric power, but worker exposures could not be predicted according to plant power consumption. Overall, electric and magnetic field levels in the three pulp and paper mills were similar to those experienced by the general population. However, maximum magnetic field intensities in some areas were as high as those experienced by electrical workers. PMID- 8209843 TI - Evaluation of professional competency in occupational hygiene in Canada--the CRBOH program. Canadian Registration Board of Occupational Hygienists. AB - The Canadian Registration Board of Occupational Hygienists (CRBOH) was established in 1986 to provide a registration system for professional occupational hygienists in Canada. It was decided that registration would be based on a competency examination following an appropriate combination of academic qualification and relevant professional experience. While the examination was being developed hygienists who met certain educational and experience requirements and who held other certifications by examination (such as those of the American Board of Industrial Hygiene, the British Examining and Board in Occupational Hygiene, or the Conseil d'Accrediation en Hygiene Industrielle du Quebec) were registered. In 1989 CRBOH, after much deliberation and review of other existing certification examinations, selected a two-part scheme consisting of both written and oral examinations. The written examination includes both multiple choice and essay style questions. Only those candidates successfully completing the written examination are eligible for the oral examination. The first group of candidates was examined in the fall of 1990. The authors outline the strengths and weaknesses of various forms of evaluation of professional competency. The rationale for the selection of the CRBOH examination format is discussed in relation to forms of evaluation currently being used in the United States and the United Kingdom. The implication of CRBOH registration on the training and education of occupational hygienists in Canada is highlighted. PMID- 8209844 TI - Imaging indoor tracer-gas concentrations with computed tomography: experimental results with a remote sensing FTIR system. AB - This work demonstrates for the first time the feasibility of computed tomography (CT) reconstructions of pollutant concentrations in a real room setting. A remote sensing Fourier transform infrared spectrometer was mounted on a moving base in a controlled ventilation chamber. A passive tracer was released from a point source into the room under constant ventilation conditions. A series of experiments gathered multiple path-averaged measurements in a two-dimensional plane for CT reconstruction. Simultaneous readings were gathered with a multiple-point sampling array for later comparison to the CT reconstructed concentrations. Good qualitative agreement between the reconstruction and point sample data was obtained. Limitations encountered due to the temporal resolution, size, and geometry of the experimental apparatus are clearly surmountable with better instrumentation. PMID- 8209845 TI - Evaluation of algorithms for tomographic reconstruction of chemical concentrations in indoor air. AB - Numerical studies were performed to evaluate and compare four different algorithms for tomographically reconstructing pollutant concentrations in indoor air measured with an optical remote sensing system. With a remote sensing/computed tomography system, two-dimensional maps of air concentrations can be created for an entire room with good spatial and temporal resolution. The success of such a system for characterizing the flow of contaminants in air, exposure assessment, and leak detection depends on the choice of tomographic reconstruction algorithm. A systematic method was developed to evaluate the performance of four algorithms: ART, ART3, SIRT, and SART. One hundred and twenty test maps were reconstructed by each algorithm under ideal and nonideal sampling conditions, and image quality was evaluated using four criteria. The nonideal sampling conditions included simulation of measurement noise and reduction in the number density of rays. Performance of the algorithms was found to be intimately related to the number of peaks in the test maps. The importance of using multiple measures of image quality was underscored by the fact that for some sampling conditions simulated, performance of the algorithms was judged differently depending on the evaluation criteria. Results indicated that using numerical studies is successful for evaluating such algorithms. PMID- 8209846 TI - Ambient noise levels in industrial audiometric test rooms. AB - In 1983 the Occupational Safety and Health Administration (OSHA) specified maximum permissible ambient noise levels (MPANLs) that would allow valid hearing threshold measurements in an audiometric test room. However, ambient noise sound pressure levels (SPLs) in rooms used for industrial hearing tests are unknown. The present study reports octave band (125 to 8000 Hz) ambient noise SPLs measured in 490 single-walled prefabricated audiometric test rooms located in industrial settings that were obtained from eight sources. The ambient noise SPLs were highest in the lower frequencies and decreased as frequency increased. All 490 rooms met the OSHA MPANLs. Fortunately, the ambient noise SPLs were considerably lower than the OSHA MPANLs, since previous research has demonstrated that hearing thresholds cannot be obtained down to 0-dB HL in a test room having ambient noise levels equal to the OSHA MPANLs. In fact, 33%, or 162 of the 490 test rooms, met the more stringent MPANLs recently specified by the American National Standards Institute (ANSI) for industrial hearing testing. Given that the OSHA MPANLs are too high and that the test room ambient noise SPLs were considerably less than the OSHA MPANLs, that authors recommend that the OSHA MPANLs be revised to the more stringent ANSI 1991 MPANLs so that hearing thresholds for baseline and annual audiograms can be measured down to 0-dB HL. PMID- 8209847 TI - Evaluation of chemical releases and worker exposures from filter press operations. AB - The exposures (inhalation and dermal) and releases (air, water, solids, and process streams) associated with the filtration of industrial wastewater sludge from an electronics manufacturing plant were characterized. Chemical releases and worker exposures for a target chemical (total copper) were measured over four operational cycles. Various aspects of the filtration operation believed to influence the measurement values were documented. Worker exposures associated with the discreet stages of the filter operation were measured. Ventilation patterns around the filter press were also monitored. The workers' time-weighted average exposures to total copper during the 113-minute operational cycle ranged from 3.1 to 25 micrograms/m3 (2.2 geometric standard deviation, 6.4 micrograms/m3 geometric mean concentration). The manual removal of filter cake comprised only 15% of the time in an average filtration cycle, but produced 72% of the workers' inhalation exposure. During this cake-removal stage, inhalation exposures ranged from 11 micrograms/m3 to 130 micrograms/m3 (2.5 geometric standard deviation, 30 micrograms/m3 geometric mean concentration). Differences in worker technique may account for the large range of inhalation exposures during the cake-removal stage. Exposures and releases were successfully determined for a single unit operation, as well as for the discreet stages of operation. The data generated will enable EPA to more accurately estimate worker exposures and chemical releases for new chemicals as required by the Toxic Substances Control Act. The approach utilized will benefit industrial hygienists in providing estimates of worker exposures and aid in the targeting of survey sampling. PMID- 8209848 TI - Strategies for determining occupational exposures in risk assessments: a review and a proposal for assessing fungicide exposures in the lumber industry. AB - To select an exposure monitoring protocol for assessing the occupational risk of fungicides in the lumber industry, the main strategies for determining exposures for risk assessment were reviewed. A survey of lumber industry work sites using fungicides observed the methods of application and opportunities for exposure. In addition, a review of existing measurement data was done. These investigations indicated that fungicide application techniques and process locations were varied from site to site, such that it would be extremely difficult to select a few representative locations for quasi-experimental studies, as is usually done in agricultural pesticide exposure assessment. Existing measurement data mainly describe exposures to fungicides no longer in use, and do not cover the range of application techniques or process technology observed in the survey. A probability sample of the exposed population was therefore proposed. PMID- 8209849 TI - The analysis of work-related injuries in a tractor factory. AB - An analysis of work-related injuries and absenteeism was carried out in a steel production and tractor manufacturing factory from 1982 to 1986. During that period there were 1152 injuries and 16,798 working days lost. Foundry workers were the most frequently injured; fists and fingers were the most frequently affected parts of the body. The number of injuries at work as well as the number of lost working days were highly influenced by the low socio-economic position of workers and by a general recession. PMID- 8209850 TI - Tuberculosis. Role of the clinical laboratory in providing rapid diagnosis and assessment of disease activity. PMID- 8209851 TI - Role of the bcl-2 oncogene in Hodgkin's disease. PMID- 8209852 TI - Overexpression of p53 protein in adenocarcinoma of the pancreas. AB - Mutations in the p53 tumor suppressor gene are frequently identified in human neoplasms. These mutations may be associated with stabilization and, therefore, with overexpression of the p53 protein product as determined by immunohistochemical staining. Using a new antigen retrieval method and a polyclonal antibody to p53 (CM-1), the authors examined 48 formalin-fixed paraffin-embedded adenocarcinomas of the pancreas for overexpression of the p53 gene product. These 48 carcinomas were obtained from a series of patients with well-documented clinical histories and extensive follow-up. The carcinomas had been analyzed previously for K-ras gene mutations, tumor ploidy, and tumor proliferating index. Specific diffuse nuclear staining for the p53 protein was identified in 19 of the 48 (40%) infiltrating carcinomas examined. Focal or negative staining was seen in the remaining 29 cases (60%). In addition, 17 of the neoplasms contained synchronous in situ carcinomas; two (12%) of these displayed diffuse nuclear staining for the p53 protein. Overexpression of p53 was associated with aneuploidy (P = .05), which had been a poor prognosticator in this series of adenocarcinomas of the pancreas. Although overexpression of p53 appeared to be associated with poor prognosis (hazard ratio, 1.8; P = .07), this was not statistically significant. Overexpression of p53 was not significantly associated with K-ras oncogene mutations or tumor proliferating index. The authors conclude that overexpression of the p53 protein occurs frequently in invasive adenocarcinomas of the pancreas and in some in situ carcinomas, as well. PMID- 8209853 TI - A comparison of human papillomavirus detection rates by dot blot assay from smear and biopsy specimens with regard to human papillomavirus type and histologic diagnosis. AB - Colposcopic biopsy and cervical smear sampling techniques for human papillomavirus (HPV) DNA dot hybridization were compared to reveal differences related to the level of the histopathologic detection of HPV type 16. The authors used a previously published dot blot assay to analyze 814 pairs of concurrent biopsy and smear DNA specimens for the presence of DNA of HPV 6, 11, 16, and 18. The overall HPV detection rate was 38%, the most prevalent type being HPV 16 (39% of all HPV-positive cases). In detection and typing of HPV DNA, a 81% concordance (658 of 814 pairs) was noted between the smear and biopsy specimens, with a significant correlation in detection of any of the HPV types in the specimens (kappa, .609). The rate of smear-negative cases among all biopsy-positive cases was similar for HPV 11 and HPV 16 (41% and 42%, respectively). Further analysis of distribution of the smear-negative and biopsy-positive cases among different histopathologic levels of disease showed no significant difference between neoplastic and nonneoplastic lesions for either virus type. In 56 cases, only the smear specimen was positive for DNA of the studied HPV types. Both biopsy and smear specimens should be used for HPV detection in cervical dysplasias. PMID- 8209854 TI - Racial and age-related differences in incidence and severity of focal autoimmune thyroiditis. AB - To determine possible racial and age-related differences of focal autoimmune thyroiditis between white and black Americans, autopsy material from American subjects was evaluated for incidence and severity of chronic lymphocytic thyroiditis. The overall incidence of lymphocytic infiltration in thyroid sections from subjects aged more than 20 years was 41.4% in white females, 20% in white males, 17.4% in black females, and 8.5% in black males. An increase to 54.8% in incidence of thyroiditis from the first decade onward was noted in white females older than 80 years of age. Age did not cause a remarkable increase in incidence of thyroiditis in white males, in black females, or black males. The susceptibility to chronic thyroiditis in American white males and females was almost the same as that of British white males and females. The incidence of thyroiditis in black females and males was similar to that in Japanese females and males. These findings showed clear racial differences in susceptibility to chronic thyroiditis. PMID- 8209855 TI - In vitro bromodeoxyuridine labeling of malignant neoplasms. A comparative study with flow cytometry cell-cycle analysis. AB - Proliferative fraction has been defined as an independent prognostic marker for some malignant neoplasms. An estimate of the proliferative fraction can be obtained by cell-cycle analysis of flow cytometric DNA measurements. However, overlapping DNA distributions of aneuploid neoplasms are difficult to analyze, even with sophisticated computer programs, and results are not always reproducible. Bromodeoxyuridine (BrdUrd) labeling followed by immunohistochemical detection has been proposed as an alternative, simple, and accurate method for identifying and counting DNA synthesizing cells. In vitro BrdUrd labeling was performed on 87 tumors, including 35 lung cancers, 25 breast carcinomas, and 27 tumors of other origin. Results were compared with flow cytometric S-phase estimates in 46 cases. Mean BrdUrd labeling of lung tumors was 8.5% +/- 5.2%, compared with a mean flow cytometric S-phase fraction of 20% +/- 18.4%. Mean BrdUrd labeling of breast carcinomas was 6.8% +/- 3.8%, compared with a mean flow cytometric S-phase fraction of 12.5% +/- 9.9%. In both tumor types, BrdUrd labeling correlated well with histologic grade. Correlation between BrdUrd labeling and flow cytometric S-phase estimates were generally poor, particularly with aneuploid tumors. PMID- 8209856 TI - Abnormal endocervical cells. Really abnormal? Really endocervical? AB - With the increasing incidence of endocervical adenocarcinoma, cytopathologists must distinguish between benign dysplastic and malignant endocervical cells. For this reason, the authors began a retrospective review of 44 cytology specimens initially interpreted as "abnormal endocervical cells of uncertain significance" and of 10 endocervical carcinomas. Cytologic specimens were categorized according to tissue into three groups: reactive cells (9), abnormalities associated with squamous intraepithelial lesions (17 low grade, 18 high grade), and adenocarcinoma (10). Reactive cells were monolayered, with demarcated cytoplasm and bland nuclei. Abnormal cells from squamous intraepithelial lesions showed crowding and irregular nuclei with smudgy or granular chromatin. Cells from adenocarcinoma showed multilayering and nuclei with clumped chromatin and occasional mitoses. On reexamination, numerous cells were found to be of metaplastic rather than endocervical origin. Surprisingly, the presence of abnormal metaplastic or endocervical cells sometimes was the only indicator of associated squamous intraepithelial lesion. PMID- 8209857 TI - Inclusion body fibromatosis of the breast. Two cases with immunohistochemical and ultrastructural findings. AB - Two cases of fibromatosis of the breast, characterized by a proliferation of spindle cells containing intracytoplasmic, spherical, eosinophilic inclusion bodies, are reported. The light and electron microscopic features, as well as the immunohistochemical features, are indistinguishable from those found in infantile digital fibromatosis. The proliferating spindle cells are characterized as myofibroblasts, whereas the inclusion bodies show an immunohistochemically nonreactive, hollow-like pattern with peripheral reactivity for actin filaments. This lesion, observed for the first time in the breast, expands the number of extradigital inclusion body fibromatoses. PMID- 8209858 TI - Use of discriminant analysis to assess disease activity in pulmonary tuberculosis with a panel of specific and nonspecific serum markers. AB - Several cell activation markers, acute phase reactants, enzymes, and antituberculous antibody serum levels have been proposed as possible markers to monitor disease activity in patients with tuberculosis. They have all shown limited sensitivity or specificity. The authors therefore attempted to generate a canonical variable using discriminant analysis, including sensitive and specific parameters, to be a reliable marker in classifying patients correctly during the course of pulmonary tuberculosis. The following parameters were selected: two soluble cell activation markers (soluble interleukin-2 receptor and sCD8); the levels of immunoglobulin (Ig) G and IgM antibodies against the A60 antigen complex; and the presence of specific antibodies directed to eight different A60 components, revealed by Western blot analysis. The tests were performed on sera from three groups of patients with pulmonary tuberculosis. The first group comprised 25 patients with onset tuberculosis, clinically active (OTCA), evaluated at the time of admission. The second group included 28 patients with chemotherapy-treated tuberculosis, clinically active (CTCA), 2 months after therapy had begun. The third group included 20 patients with tuberculosis, nonclinically active (TNCA), who had had at least 1 year of effective therapy. The authors obtained an 80.9% rate of correct classification for the three groups and a rate of 100% when OTCA and TNCA were compared. The patients with CTCA were scarcely differentiated and tended to be distributed into the two other groups. To improve the separation between patients with CTCA and those with OTCA, a second canonical variable was generated with a 91.7% rate of correct classification, as compared with 71% obtained using the sCD8 as the best single variable. The mean values of the last canonical variable were statistically different (Mann-Whitney test, P = .049) when stratified for acid fast bacilli positive or negative CTCA patients (microscopic detection). Three patients, followed during the entire course their disease, were, as expected, correctly positioned with respect to the subsequent disease phases. PMID- 8209859 TI - Evaluation of the new DrySlide beta-lactamase test. AB - Four hundred thirteen recent clinical isolates of Staphylococcus, Haemophilus, Moraxella, and Neisseria species were tested for beta-lactamase production using the Difco DrySlide beta-lactamase test. These results were compared with those of the BBL Cefinase reagent. Of the 413 isolates tested, 258 (62.5%) were beta lactamase positive. There was 99.8% agreement between the two test methods; only one isolate of Staphylococcus aureus was DrySlide-negative and Cefinase-positive. The DrySlide beta-lactamase reagent is an accurate and convenient format for the evaluation of beta-lactamase activity in the clinical laboratory. PMID- 8209860 TI - The effects of nonclassic pediatric bacterial pathogens on the usefulness of the Directigen latex agglutination test. AB - Haemophilus influenzae type b, Escherichia coli, Neisseria meningitis, Streptococcus agalactiae, and Streptococcus pneumoniae are classically the predominant meningeal pathogens of children. The Directigen latex agglutination test identifies these pathogens by detecting specific antigens in cerebrospinal fluid (CSF) and urine. The authors tested 1151 specimens from 791 children with suspected meningeal infections. They found that the sensitivity of the Directigen test for detecting the five classic CSF pathogens of children was 83.3% with CSF and 60% with urine specimens. In detecting all pathogens, however, the sensitivity was only 50% with CSF and 37.5% with urine. Thus, an increased prevalence of nonclassic pathogens in a pediatric population adversely affects the efficacy of the Directigen test for confirming a diagnosis of meningitis and emphasizes the diagnostic importance of the clinical history and other routine CSF tests. PMID- 8209861 TI - A search for mycobacterial DNA in sarcoidosis using the polymerase chain reaction. AB - The etiology of sarcoidosis is unknown, but mycobacteria have been considered as a possible etiologic agent. The authors used the polymerase chain reaction (PCR) to search for mycobacterial DNA in paraffin-embedded granulomatous tissues from patients with sarcoidosis. The target sequence used for PCR amplification is a 383-base pair segment of the gene encoding the 65 kD mycobacterial surface antigen. This assay can detect Mycobacterium tuberculosis and atypical mycobacteria in archival material. Its sensitivity, which is superior to Ziehl Nielsen staining for acid-fast bacilli, is 1 bacterium per 2500 cells. Ten sarcoidosis blocks and 10 normal controls were negative with mycobacterial PCR but positive with beta-actin PCR, indicating the presence of amplifiable DNA. Mycobacterial PCR gave positive results for six acid-fast bacilli stain/culture positive blocks from patients with tuberculosis. These results indicate that sarcoidosis probably does not represent an active mycobacterial infection. These data also suggest that mycobacterial PCR is helpful in differentiating tuberculosis and sarcoidosis. PMID- 8209862 TI - The utility of latex agglutination assays in the diagnosis of pediatric viral gastroenteritis. AB - To design a rapid and efficient protocol for processing pediatric stool specimens, the authors used 434 specimens to evaluate two commercial latex assays to detect rotavirus (Meritec-Rotavirus and Rotalex) and one to detect adenovirus (Adenolex). Rotavirus latex assay results were compared with electron microscopic examination and adenovirus latex assay results with virus culture. Ninety-two specimens (21%) were positive for rotavirus and 28 (6.5%) for adenovirus; 5 (1%) had both viruses. The sensitivity, specificity, positive predictive values, and negative predictive values for the three assays were, respectively, as follows: Meritec-Rotavirus (97%, 99%, 97%, 99%), Rotalex (91%, 99%, 94%, 98%), and Adenolex (46%, 99%, 77%, 97%). For primary rotavirus screening, the Meritec Rotavirus and Rotalex latex assays offer a good alternative to electron microscopic examination. For primary adenovirus screening, the low sensitivity of the Adenolex latex assay precludes its use as a routine screen. Its excellent specificity, however, makes it a useful tool for culture confirmation. PMID- 8209863 TI - Evaluation of immunoperoxidase techniques to detect Rickettsia rickettsii in fixed tissue sections. AB - Standard immunoperoxidase techniques were evaluated in the diagnosis of Rocky Mountain spotted fever (RMSF). Formalin-fixed, paraffin-embedded tissue was tested to detect Rickettsia rickettsii using the same antibody provided by the Centers for Disease Control and Prevention that is used for direct immunofluorescence (DIF). Tissues from 23 patients with suspected RMSF were divided: some were snap-frozen for DIF; the remainder were fixed in formalin, processed routinely, and embedded in paraffin for immunoperoxidase and hematoxylin and eosin staining. Ten patients were ultimately determined to have RMSF; in nine of these patients, both DIF and immunoperoxidase staining were positive for R rickettsii. There were no discrepancies, positive or negative, between the two methods. In the one case with a false-negative result by both methods, the patient had received antirickettsial antibiotics 72 hours before the biopsy was performed. These data demonstrate that the immunoperoxidase technique is effective in diagnosing RMSF and may be applied to cases retrospectively. PMID- 8209864 TI - Use of semiquantitative human immunodeficiency virus type 1 culture to guide therapy in a premature infant. AB - Semiquantitative cultures for human immunodeficiency virus type 1 were used to initiate and guide therapy in an asymptomatic, heavily infected premature infant. The cultures were performed on fivefold serial dilutions of peripheral blood mononuclear cells, and viral growth was detected by the appearance of p24 antigen in the supernatant. While the patient was receiving low-dose zidovudine, her titer diminished from 206 infectious units per 10(6) cells to undetectable levels over 20 weeks, and she remained asymptomatic throughout her 1st year of life. This case suggests that semiquantitative HIV-1 culture should be further evaluated for its ability to guide practical therapeutic decisions in patients who do not fulfill currently established criteria for treatment. PMID- 8209865 TI - Bcl-2 rearrangement in Hodgkin's disease and reactive lymph nodes. AB - The chromosomal translocation t(14;18)(q32;q21), which involves the bcl-2 oncogene, occurs in most follicular lymphomas. Recent evidence suggests that this translocation occurs in Hodgkin's disease, linking its cellular origin and oncogenesis to follicular non-Hodgkin's lymphomas. Using polymerase chain reaction, the authors examined both Hodgkin's disease (n = 60) and reactive lymph nodes (n = 34) for the presence of bcl-2/JH breakpoint fragments, which are indicative of the t(14;18) chromosomal translocation in the major breakpoint region of the bcl-2 gene. The translocation was detected in approximately 10% of both Hodgkin's disease and nonmalignant reactive lymph node cases. These results suggest the possibility that the translocation may occur in the reactive component of Hodgkin's disease and not in the putative malignant cells, the Reed Sternberg cells. Furthermore, the detection of the translocation in reactive lymph nodes suggests that it may not be the primary factor in the oncogenesis of follicular lymphoma. PMID- 8209866 TI - Follicular dendritic cells have prognostic relevance in Hodgkin's disease. AB - The authors' previous study showed the presence of follicular dendritic cell (FDC) networks--though altered--in neoplastic areas, not only in the nodular lymphocyte predominance type, but also in other types of Hodgkin's disease. The present retrospective study was performed on 102 patients to determine whether the presence or absence of FDC networks, or parts of them, in neoplastic areas has prognostic relevance in Hodgkin's disease. Follicular dendritic cells were visualized with the monoclonal antibody Ki-FDC1P, which selectively stains FDCs in paraffin-embedded tissues. Univariate statistical analysis, in which nodular sclerosis (NS) and mixed cellularity (MC) types were combined, showed three prognostically different groups: the best prognosis was associated with nodular lymphocyte predominance cases; the worst with FDC-negative NS or MC cases; and an intermediate prognosis with FDC-positive NS or MC cases. In the NS group, the prognosis of FDC-positive cases was better than that of FDC-negative cases. After multivariate analysis, stepwise modeling identified three prognostic factors at diagnosis: stage (P = .001), FDC status (P = .001), and age (P = .06). The authors conclude that in the most common types of Hodgkin's disease (nodular lymphocyte predominance, NS, and MC), FDC status in the neoplastic area(s) bears prognostic relevance, a positive FDC status predicting a favorable prognosis and a negative FDC status an unfavorable one. PMID- 8209867 TI - High frequency of Epstein-Barr virus latent membrane protein-1 expression in acquired immunodeficiency syndrome-related Ki-1 (CD30)-positive anaplastic large cell lymphomas. Italian Cooperative Group on AIDS and Tumors. AB - Immunohistochemical detection of Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP-1) was used to identify EBV-associated Ki-1-positive anaplastic large-cell (ALC) lymphomas occurring in 11 patients with and 29 patients without human immunodeficiency virus (HIV) infection. In addition, 18 representative cases of other acquired immunodeficiency syndrome (AIDS)-related lymphomas and 66 cases of Hodgkin's disease, including 14 patients with HIV infection, were investigated. In patients with HIV infection, LMP-1 was found more frequently in Ki-1-positive ALC lymphomas than in other histotypes, although the difference in EBV association between Ki-1-positive ALC and other lymphomas was not significant. In these patients, the percentage of LMP-1 expressing Ki-1-positive ALC lymphomas was significantly higher than that found in patients without HIV infection (72.7% vs. 24.1%; P < .01), thus suggesting an etiologic role for EBV in a large proportion of AIDS-related Ki-1-positive ALC lymphomas. Moreover, the frequency of LMP-1 expression in Hodgkin's disease cases (71.4% in patients with and 21.1% in patients without HIV infection) was close to that found in Ki-1 positive ALC lymphoma cases, supporting the view that the higher frequency of EBV association with both entities detected in patients with HIV infection may be AIDS-related. PMID- 8209868 TI - Immunophenotypic and genotypic analysis of acquired immunodeficiency syndrome related non-Hodgkin's lymphomas. Correlation with histologic features in 36 cases. French Study Group of Pathology for HIV-Associated Tumors. AB - High-grade B-cell-type non-Hodgkin's lymphomas are observed in 5% to 8% of patients positive for the human immunodeficiency virus. Nearly all cases belong to one of the three major histologic types: centroblastic or large noncleaved cell, immunoblastic and Burkitt's lymphoma, or small noncleaved cell. Some cases that are polymorphic are termed high-grade B-cell, not otherwise specified (NOS). The authors determined the immunophenotype of each histologic category of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkins' lymphoma and sought a relationship with the presence of the Epstein-Barr virus (EBV). B-cell differentiation antigens, activation marker expression (human leukocyte antigen DR, CD10, CD19, CD20, CD21, CD22, CD23, CD25, CD30, CD38), and epithelial membrane antigen were analyzed. The clonality was determined by the detection of cytoplasmic immunoglobulin, surface immunoglobulin, and the analysis of joining region (JH) immunoglobulin gene configuration by Southern blot. Epstein-Barr virus was detected either by Southern blot analysis using BamHI W probe fragment or by in situ hybridization with EBV-encoded RNA transcripts-1 specific probe. The immunophenotypic and genotypic results were compared with the morphology results and with the presence or absence of EBV. Burkitt's lymphomas were associated with EBV in 50% of cases, were monoclonal, and expressed mostly immunoglobulin (Ig) MK, CD10, CD19, CD20, CD22, and CD38. This immunophenotypic profile closely resembled those of the centroblastic cases (large noncleaved cell), in which EBV was absent. Epstein-Barr virus was associated with 90% of immunoblastic cases, and only CD10, CD20, and CD38 were expressed. CD71 was expressed in all categories of non-Hodgkin's lymphoma, and CD21 and CD23 were rarely expressed. Two cases of immunoblastic lymphoma and one case of high-grade B-NOS were polyclonal regarding JH rearrangement, but EBV tested with 1.9-Kb Xhol fragment was clonal. No significant immunophenotypic changes were noted in relation to the presence of EBV. Such studies comparing morphology, immunophenotype, and genotype could help classify and better understand the pathogenesis of AIDS-related non-Hodgkin's lymphoma. PMID- 8209869 TI - Primary lymphoma and Paget's disease of the femur. AB - Malignant neoplasms associated with Paget's disease of the bone are most commonly metastatic and rarely primary malignant transformations. Sarcomatous transformations, such as osteogenic sarcoma, predominant in Paget's disease. The authors discuss the synchronous and synostotic occurrence of a primary lymphoma of bone in association with Paget's disease. The simultaneous occurrence of isolated primary lymphoma of bone and its phenotype in association with Paget's disease in the femur, which had not been rigorously documented in the previous literature, is reported. PMID- 8209870 TI - Thin-layer chromatography of the N-propyl and isopropyl homologs of cocaine. PMID- 8209871 TI - Noncomedo ductal carcinoma in situ. PMID- 8209872 TI - Prospective study of cigarette smoking and the risk of developing idiopathic Parkinson's disease. AB - A 26-year follow-up study of 8,006 men enrolled in the Honolulu Heart Program examined the effect of cigarette smoking on the risk of developing idiopathic Parkinson's disease. Cases were identified through an ongoing search of hospital records and by the review of death certificates and medical records of local neurologists. Men who had smoked cigarettes at any time prior to study enrollment in 1965 had a reduced risk of developing idiopathic Parkinson's disease (relative risk = 0.39). Examination of smoking by pack-years revealed an apparent dose response effect on the risk of idiopathic Parkinson's disease, but not on the age of onset. Coffee drinking was also associated with reduced risk, apparently because of its association with cigarette smoking. Although the detrimental health effects of cigarette smoking would far outweight any possible protective effect for smoking and Parkinson's disease, the association of smoking with apparent protection may contribute to understanding the underlying pathogenetic mechanisms. PMID- 8209873 TI - Maternal smoking during pregnancy as a predictor of lung function in children. AB - Recent studies have suggested that prenatal exposure to environmental tobacco smoke may lead to lower lung function in infants. The authors examined the relation of maternal smoking during pregnancy to persistent deficits in the lung function of older children. Subjects were 8,863 nonsmoking white children aged 8 12 years from 22 North American communities. Information on maternal smoking was provided by the child's mother. Pulmonary function testing of the children was conducted at school in 1988-1991. Children whose mothers smoked during pregnancy, whether or not they still smoked in the year prior to the study, had significantly lower lung function than did children whose mothers did not smoke in either period. On average, forced expiratory flow between 65 and 75 percent of forced vital capacity (FEF65-75%), forced expiratory flow between 25 and 75 percent of forced vital capacity (FEF25-75%), and forced expiratory volume in 3/4 of a second (FEV0.75) were 5.7%, 4.9%, and 1.7% lower, respectively, for children whose mothers smoked during pregnancy. After adjusting for maternal smoking during pregnancy, the authors found that current maternal smoking was not associated with significant differences on any lung function measure. These results show a persistent deficient in lung function associated with maternal smoking during pregnancy that is not explained by current maternal smoking alone. The strongest effects were observed with pulmonary function measures of flow in the small airways. The authors conclude that the effects of exposure to tobacco smoking by the mother during pregnancy and/or environmental tobacco smoke exposure in the first few years of life persist into childhood and may affect the pulmonary function attained throughout the child's life. PMID- 8209874 TI - Risk factors for the transition from noninjection to injection drug use and accompanying AIDS risk behavior in a cohort of drug users. AB - Although injection drug users have been shown to reduce high-risk injection behaviors in response to the epidemic of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), the total elimination of risk behaviors has not been achieved. A more fundamental preventive measure may be to keep drug users from starting to inject at all. The authors selected 184 drug users from a cohort study in Amsterdam, the Netherlands, from 1985 to 1992, who had reported at entry to the study that they either had never injected drugs or had injected for the last time more than 1 year before the initial visit. Over a 5-year follow-up period, impressively high cumulative rates of transition to injection drug use were found in both groups. Among drug users who had never injected drugs, 30% began injecting; among those who had injected drugs 1-5 years before their entry into the study, 70% started injecting again. These rates were stable over time. The authors also confirmed that new injectors are at high risk of acquisition of HIV infection. With the use of a survival and a nested case control analysis, the following independent risk factors that increased the likelihood of starting to inject were found: previous injecting history, ethnicity other than Surinamese/Antillean, regular long-term use of cocaine, current use of heroin, and a current steady sexual relationship with a partner who injects drugs. Given the high and stable incidence of initiation of injection among drug users within the cohort study, the prevention of this behavior appears to be difficult. Additional studies are needed to determine effective prevention strategies. PMID- 8209875 TI - Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study. AB - The prevalence of subclinical atherosclerosis and cardiovascular disease was evaluated among the 5,201 adults aged > or = 65 years in four communities participating in the Cardiovascular Health Study from June 1989 through May 1990. A combined index based on electrocardiogram and echocardiogram abnormalities, carotid artery wall thickness and stenosis based on carotid ultrasound, decreased ankle-brachial blood pressure, and positive response to a Rose Questionnaire for angina or intermittent claudication defined subclinical disease. The prevalence of subclinical disease was 36% in women and 38.7% in men and increased with age. Among women, low-density lipoprotein cholesterol, systolic blood pressure, blood glucose, and cigarette smoking were positively associated, and high-density lipoprotein cholesterol negatively associated, with subclinical disease. In men, systolic blood pressure, blood glucose, and cigarette smoking were independent risk factors in multiple logistic regression analyses. The risk factors for subclinical disease are, therefore, similar to those for clinical disease at younger ages, especially among women. It is possible that older individuals with subclinical disease are at very high risk of developing clinical disease and that more aggressive interventions to prevent clinical disease should be oriented to individuals with subclinical disease. PMID- 8209876 TI - Antioxidant vitamin intake and coronary mortality in a longitudinal population study. AB - Oxidation of lipoproteins is hypothesized to promote atherosclerosis and, thus, a high intake of antioxidant nutrients may protect against coronary heart disease. The relation between the intakes of dietary carotene, vitamin C, and vitamin E and the subsequent coronary mortality was studied in a cohort of 5,133 Finnish men and women aged 30-69 years and initially free from heart disease. Food consumption was estimated by the dietary history method covering the total habitual diet during the previous year. Altogether, 244 new fatal coronary heart disease cases occurred during a mean follow-up of 14 years beginning in 1966 1972. An inverse association was observed between dietary vitamin E intake and coronary mortality in both men and women with relative risks of 0.68 (p for trend = 0.01) and 0.35 (p for trend < 0.01), respectively, between the highest and lowest tertiles of the intake. Similar associations were observed for the dietary intake of vitamin C and carotenoids among women and for the intake of important food sources of these micronutrients, i.e., of vegetables and fruits, among both men and women. The associations were not attributable to confounding by major nondietary risk factors of coronary heart disease, i.e., age, smoking, serum cholesterol, hypertension, or relative weight. The results support the hypothesis that antioxidant vitamins protect against coronary heart disease, but it cannot be excluded that foods rich in these micronutrients also contain other constituents that provide the protection. PMID- 8209877 TI - Revision of dietary analysis software for the Health Habits and History Questionnaire. AB - The software for analysis of the Health Habits and History Questionnaire (HHHQ) has been revised and is available to researchers. As in earlier versions of the software, questionnaires other than the standard National Cancer Institute versions can be analyzed. Foods can be added or dropped, nutrients can be added or changed, and many other revisions and options are facilitated. Estimates of 33 nutrients and up to 20 user-defined food groups are produced. The validity is unchanged from the previous software. Other features include a data entry key-and verify system, standardized editing, a computer-assisted interview, and the calculation of health indices including pack-years of smoking and social network index. PMID- 8209878 TI - Validation of the Minnesota Leisure Time Physical Activity Questionnaire in Spanish men. The MARATHOM Investigators. AB - Questionnaires are frequently used for measuring physical activity. The aim of this study was to validate the Spanish version of the Minnesota Leisure Time Physical Activity Questionnaire (MLTPAQ) in Spanish men. Healthy men (n = 187) aged 20-60 years were recruited. The MLTPAQ was administered to assess the quantity (total activity metabolic index) and quality (heavy, moderate, and light) of physical activity performed in the last year, quarter, month, and week. Fitness was assessed with an exercise test. Spearman's correlation coefficients between the total activity metabolic index and exercise test duration, time to maximal theoretical heart rate, and caloric intake were 0.57, 0.46, and 0.40, respectively. The intraclass correlation coefficients between the total activity metabolic indexes in the last year and in the last quarter, month, and week were 0.62, 0.46, and 0.35, respectively. In multiple linear regression, the heavy, moderate, and light activity metabolic index, age, body mass index, and basal heart rate explained 40% of the variability of time to the maximum theoretical heart rate. The Spanish version of the MLTPAQ is a valid instrument to measure the quantity and quality of physical activity performed in the last year (also in periods shorter than 1 year) by Spanish men aged 20-60 years. Only heavy physical activity is related to cardiorespiratory fitness. PMID- 8209879 TI - A meta-analysis of colorectal cancer and asbestos exposure. AB - A meta-analysis of the relation between asbestos exposure and colorectal cancer mortality was conducted, using published reports of 20 asbestos-exposed cohorts. Summary standardized mortality ratios (SMRs) for colorectal cancer were examined in relation to asbestos type and estimates of dust exposure (as direct estimators of asbestos exposure) and in relation to lung cancer SMR and the proportion of all deaths due to mesothelioma (as proxy estimators of asbestos exposure). An elevated summary SMR was observed in cohorts exposed to amphibole asbestos (summary SMR = 1.47; 95% confidence interval (CI) 1.09-2.00), but not in cohorts exposed to serpentine asbestos (summary SMR = 1.04; 95% CI 0.81-1.33) or in cohorts exposed to both serpentine and amphibole asbestos (summary SMR = 1.03; 95% CI 0.74-1.42). Cohorts having a lung cancer SMR greater than 2.00 had a summary SMR of 1.51 (95% CI 1.29-1.76), and cohorts in which more than 1% of all deaths were attributed to mesothelioma had a summary SMR of 1.24 (95% CI 0.94 1.64). After stratifying the cohorts based on mortality due to all cancers excluding those known or suspected to be associated with asbestos exposure, lung cancer mortality was not clearly associated with colorectal cancer mortality, suggesting that the crude association between these factors may be due to misdiagnosis of lung cancer as other types of cancer in the reported causes of death. These results suggest that exposure to amphibole asbestos may be associated with colorectal cancer, but these findings may reflect an artifact of miscertification of cause of death. The results also suggest that serpentine asbestos is not associated with colorectal cancer. PMID- 8209880 TI - Re: "Arsenic ingestion and internal cancers: a review". PMID- 8209881 TI - Autosomal recessive colobomatous microphthalmia. AB - Colobomatous microphthalmia was studied in multiple relatives of 5 families. In these families, the disorder was an autosomal recessive trait as opposed to the usual autosomal dominant form of the disorder. A relatively high incidence of this recessive allele is found in the Iranian Jewish community. PMID- 8209882 TI - Parental consanguinity in two sibs with omodysplasia. AB - Two sibs with omodysplasia were born to phenotypically normal but consanguineous parents. They had severe micromelic dwarfism, facial anomalies, and mental retardation. One had a congenital heart defect. The radiographic findings are typical: hypoplastic distal end of the humerus with radioulnar diastasis. Parental consanguinity and clinical manifestations in 2 sibs suggest autosomal recessive inheritance. PMID- 8209883 TI - Juvenile variant of Schimke immunoosseous dysplasia. AB - We report on a 16-year-old girl with spondyloepiphyseal dysplasia, nephrotic syndrome, lymphopenia, and signs of defective cellular immunity. The manifestations are very similar to those reported by Spranger et al. [1991: J. Pediatr 119: 64-72] as Schimke immunoosseous dysplasia, except for age of onset. In Schimke immunoosseous dysplasia, growth retardations as an initial symptom is noted in early childhood and about 1 year after onset of progressive proteinuria. In our case the skeletal abnormality was noted at age 10 years as dislocation of the hip joints and the diagnosis of nephrotic syndrome was made at age 16 years. The findings strongly suggest that our patient has a juvenile variant of Schimke immunoosseous dysplasia. PMID- 8209884 TI - Spondyloepiphyseal dysplasia with nephrotic syndrome (Schimke immunoosseous dysplasia). AB - The first symptoms of immunooseous dysplasia were growth retardation and myopia. Nephrotic syndrome was diagnosed at the age of 8 years. Skeletal roentgenograms showed spondyloepiphyseal dysplasia. In the renal biopsy there was nodular accumulations of PAS-positive hyaline material at the base of the granular stalks. There was lymphopenia with decreased CD4 and CD8 subpopulations. The condition of the patient gradually worsened until she died unexpectedly at 10 years with clinical symptoms of encephalitis. Autopsy documented cytomegaloviral pneumonia and advanced mesangioproliferative glomerulonephritis. In the spleen there was PAS-positive hyaline material massively infiltrating the walls of the central arterioles of the splenic follicles. There was marked depletion of lymphocytes in the spleen and in lymph nodes. The differential diagnosis of immunooseous dysplasia in the framework of spondyloepiphyseal dysplasia is discussed. PMID- 8209885 TI - Preaxial brachydactyly with abduction of thumbs and hallux varus: a distinct entity. AB - We describe a father and his daughter who had a unique pattern of preaxial brachydactyly, and unusual facial appearance. Both had short broad abducted thumbs and halluces. The second digits of both hands were also short and broad and those of feet were medially angulated. The radiographic findings were short first metacarpals and first metatarsals and hypoplastic phalanges of first two digits of hands and feet. A similar pattern of brachydactyly was described by Christian et al. [1972: Am J Hum Genet 24:694-701] and Mononen et al. [1992: Am J Med Genet 42: 706-713]. Our patients differ from those described by Christian et al. in that they did not have any mental retardation and from those of Mononen et al. by the absence of short stature and epiphyseal and metaphyseal changes. The heterogeneity of this new type of brachydactyly remains to be resolved. PMID- 8209886 TI - Another family with tricho-rhino-phalangeal syndrome type III (Sugio-Kajii syndrome). AB - Tricho-rhino-phalangeal syndrome Type III (TRPS III) is a newly defined genetic entity. Only 9 patients in a family and one sporadic patient have been reported. We add another family in which 4 individuals in 3 generations are affected with this autosomal dominant trait. Although they manifested short stature, sparse hair, "pear-shaped" nose, and cone-shaped epiphyses, sharing these findings with TRPS Type I, the presence of a severe form of generalized shortness of all phalanges and metacarpals, and the absences of mental deficiency and exostoses in this family distinguish the disorder from the TRPS Types I and II. Their manifestations are quite similar to those of the patients reported as TRPS III (Sugio-Kajii syndrome). PMID- 8209887 TI - Familial 10p trisomy resulting from a maternal pericentric inversion. AB - We report a familial recombination of a pericentric inversion of chromosome 10 resulting in 2 affected relatives who had 10p trisomy and 10q monosomy with the karyotypic abnormality designated rec(10) dup p,inv(10) (p11.2q26). Both of these individuals had the typical characteristics of 10p trisomy, however, at birth the proposita had mild facial anomalies suggesting that the distinct facial characteristics may be of postnatal onset in some cases. In addition, the proposita had gastroesophageal reflux causing severe anemia. The phenotype of our patients is compared to 41 patients with 10p trisomy reported in the literature. PMID- 8209888 TI - Unbalanced 5;16 translocation in a boy with papillary thyroid carcinoma. AB - This is the first reported case of an unbalanced chromosome rearrangement resulting in trisomy 5q35.5-->qter and monosomy 16p 13.3-->pter, in a boy with mental and growth retardation, minor anomalies, and a history of bilateral papillary thyroid carcinoma. This was the result of a familial balanced translocation. The clinical and cytogenetic manifestations of the case are presented and the possible role of the chromosomal rearrangement in the etiology of the thyroid carcinoma is discussed. PMID- 8209889 TI - Diffusion of information about neurofibromatosis type 1 DNA testing. AB - There is little information available as to how individuals with genetic disorders receive information about the availability of DNA tests and what effect this has on their utilization. The purpose of this study was to survey centers where some individuals with neurofibromatosis type 1 (NF 1) are cared for, to establish how this type of information was disseminated. In 1990 announcement of the availability of testing for familial NF 1 was published in a newsletter of the National Neurofibromatosis Foundation (NNFF) and sent to individuals with NF 1 or NF 2 and their families, professionals, and NF centers in North America. Two years later these centers were surveyed to determine whether they had notified their patients of test availability. Of the 46 responding centers, 65% indicated they had attempted to notify their patients. The majority (80%) notified patients on an individual basis in clinic. The rest did so either on an individual basis in the clinic or by telephone or by letter or by a combination of these. Based on a survey response rate of 56% and approximately 1,000 enquiries received by the NNFF from families and physicians, it is concluded that 1) factors other than knowledge of test availability determined whether DNA testing for NF 1 was utilized; 2) some centers used testing more frequently than others; 100% of the referrals came from 40% of the centers, with 15% of referrals coming from a single center; 3) a significant percentage (35%) of NF centers did not inform their patients that DNA testing was available. PMID- 8209890 TI - Investigation of thermoregulatory characteristics in patients with Prader-Willi syndrome. AB - A survey instrument is used to assess temperature regulation characteristics in children with Prader-Willi syndrome (PWS) compared to 3 control groups: sibs of PWS patients (SIB), neurodevelopmentally handicapped children (ND), and age and gender matched well children (WC). Significant differences were found between PWS patients, SIB controls, and WC controls in the prevalence of febrile convulsions, fever-associated symptoms, and temperature less than 94 degrees F. No differences were noted in any variable between the PWS patients and the ND controls, suggesting that these abnormalities are not unique to PWS, but can occur in any neurodevelopmentally handicapped individual, further suggesting these do not necessarily reflect syndrome-specific hypothalamic abnormalities. PMID- 8209891 TI - Brachyolmia: an autosomal dominant form. AB - We have investigated a mother and son of South African Xhosa stock who presented with short-trunk dwarfism and kyphoscoliosis. Radiographs show the marked platyspondyly and vertebral irregularity characteristic of brachyolmia. Our patients provide further evidence for the existence of an autosomal dominant form and supports the theory of heterogeneity in this rare group of genetic skeletal disorders. Molecular investigations in this South African family are currently underway but at present the basis defect of brachyolmia remains unknown. PMID- 8209892 TI - Delineation of the da-Silva syndrome. AB - We present a 6-month-old boy with agenesis of the corpus callosum, hypertonicity, severe growth and psychomotor retardation, microcephaly, large prominent ears, and delayed bone age. Similarity of his manifestations to these in 3 sibs described by da-Silva in 1988 suggests initial delineation of the da-Silva syndrome. PMID- 8209893 TI - Population screening for carrier status: effects of test limitations on precision of carrier prevalence rates. AB - Because of genetic heterogeneity and ambiguity of test results, only rarely will carrier screening identify all carriers of a given autosomal recessive disorder. However, the fraction of carriers identified by the test can be estimated in a case frequency study. The population carrier rate then is the rate observed in a population screening study divided by the fraction of all defective alleles detected by the screening test, estimated in the case frequency study. For example, suppose 3% of a population are found to carry the delta F508 mutation for cystic fibrosis (CF) during population screening. If a case frequency study in this same population finds that 75% of the alleles of CF cases represent the delta F508 mutation, then the estimated population carrier rate is 4% (= .03/.75). The precision of this estimate involves the precision of both the fraction of carriers detected in the case frequency study and the proportion of carriers observed in the population screening study. Standard formulae for estimating the confidence interval and sample size consider only the variability in the population screening study. Since these formulae underestimate the true variability of the estimate of the population carrier rate, the sample size calculated for a population screening study is also underestimated. We present formulae which incorporate the variability in both factors, and illustrate the effect of this additional variability on confidence limits for estimates and sample size when planning a study. PMID- 8209894 TI - Restoration of half the normal dystrophin sequence in a double-deletion Duchenne muscular dystrophy family. AB - Two male cousins with Duchenne muscular dystrophy were found to have different maternal dystrophin gene haplotypes and different deletion mutations. One propositus showed two noncontiguous deletions--one in the 5', proximal deletional hotspot region, and the other in the 3', more distal deletional hotspot region. The second propositus showed only the 5' deletion. Using multiple fluorescent exon dosage and fluorescent multiplex CA repeat linkage analyses, we show that the mother of each propositus carries both deletions on the same grandmaternal X chromosome. This paradox is explained by a single recombinational event between the 2 deleted regions of one of the carrier's dystrophin genes, giving rise to a son with a partially "repaired" gene retaining only the 5' deletion. PMID- 8209895 TI - Jarcho-Levin syndrome: unusual survival in a classical case. AB - Spondylothoracic dysostosis, or Jarcho-Levin syndrome, together with spondylocostal dysostosis, constitute a heterogeneous group of rare disorders characterized by short-neck, short-trunk dwarfism and multiple vertebral anomalies at all levels of the vertebral column. The latter include hemivertebrae, fused, hypoplastic, and "butterfly" vertebrae. In most cases of Jarcho-Levin syndrome, the small size of the thorax causes respiratory death in infancy. This report of a Puerto Rican child with spondylothoracic dysostosis and unusually long survival to 11 years exemplifies the nosologic and prognostic difficulties associated with this syndrome. PMID- 8209896 TI - Stratton-Parker syndrome: confirmation of a new entity. AB - Recently, Stratton and Parker [Am J Med Genet 32:169-173, 1989] reported on a child with a previously undescribed combination of growth hormone deficiency, wormian bones, dextrocardia, brachycamptodactyly, and other midline defects. We report on another patient with similar clinical signs. PMID- 8209897 TI - McKusick-Kaufman syndrome associated with esophageal atresia and distal tracheoesophageal fistula: a case report and review of the literature. AB - A female infant with McKusick-Kaufman syndrome associated with esophageal atresia and distal tracheoesophageal fistula is presented. To the best of our knowledge, this is the second report in the literature of this association. PMID- 8209898 TI - Additional case of opsismodysplasia supporting autosomal recessive inheritance. AB - The authors describe clinical and radiological findings in a 2-year-old boy from consanguineous parents. A diagnosis of opsi(s)modysplasia (= delayed maturation) had been made (MIM 258480). The purpose of this paper is to draw attention to the striking radiological manifestations. Consanguinity in the parents of our case and occurrence in a brother and sister in a previous report support an autosomal recessive transmission. PMID- 8209899 TI - Alveolar synechia-ankyloblepharon-ectodermal defects likely CHANDS. PMID- 8209900 TI - Tricho-rhino-phalangeal syndrome type III. PMID- 8209901 TI - Facial palsy and cranial nerve abnormalities in CHARGE association. PMID- 8209902 TI - Presymptomatic testing for Huntington disease: reply to Sharpe. PMID- 8209903 TI - Thrombocytopenia in the Brachmann-de Lange syndrome. PMID- 8209904 TI - Acalvaria and occipital scalp defects. PMID- 8209905 TI - Another way to interpret the description of the Monster of Ravenna of the sixteenth century. PMID- 8209906 TI - Biparental inheritance of chromosome 21 polymorphic markers indicates that some Robertsonian translocations t(21;21) occur postzygotically. AB - Robertsonian translocations between acrocentric chromosomes are the most common structural chromosomal rearrangements in humans and many other organisms, and several mechanisms for their formation have been proposed. We have analyzed highly informative DNA polymorphisms in a family with a non-mosaic de novo Robertsonian translocation 21q;21q, to determine the parental origin of the two 21q arms of the rearranged chromosome. The genotypes indicated a biparental origin, i.e. one 21q was paternal and the other maternal. These results imply that in some cases the formation of the rob(21q;21q) occurs in the zygote or in the first few postzygotic mitotic divisions. PMID- 8209907 TI - Coincident DiGeorge anomaly and renal agenesis and its relation to maternal diabetes. AB - We describe 2 cases of DiGeorge anomaly with bilateral renal agenesis-one, who also had hemivertebrae, in an infant of an insulin-dependent diabetic mother (IDDM). In a review we identified 2 other instances of this combination, both in IDDMs. The currently accepted notion that DiGeorge anomaly and renal agenesis are developmental field defects, coupled with their coincidence in IDDM, suggests that this combination is an association. PMID- 8209908 TI - Further delineation of the Beemer-Langer syndrome using concordance rates in affected sibs. AB - Six familial cases of the Beemer-Langer syndrome (BLS) were analyzed to further elucidate the spectrum and frequency of anomalies observed in this disorder. Preaxial polydactyly was found in 3/6 affected sibs, and, therefore, its frequency previously may have been underestimated. Some patients, described as infants affected with the Majewski syndrome (MS) or "atypical" short rib polydactyly conditions, may indeed have BLS. A high frequency of brain defects (16/26) and cleft tongue, oral frenula, and/or natal teeth (13/29) widens the list of typical findings in this syndrome. The specific type of tibial defect seems to be the most important discrimination of the MS and the BLS. PMID- 8209909 TI - Congenital heart defects in Aarskog syndrome. AB - We report on 10 Japanese individuals from 3 families affected with Aarskog syndrome. Pulmonary stenosis and ventricular septal defect with spontaneous closure were detected respectively, in 2 of them as an uncommon finding. A review documented 169 non-Japanese cases (2 with congenital heart defects), while of 30 Japanese individuals reported till now, 4 (including ours) had cardiac anomalies. We propose that this combination is not coincidental and that in all cases of Aarskog syndrome a cardiac evaluation is indicated. PMID- 8209910 TI - Recombinant chromosome 18 resulting from a maternal pericentric inversion. AB - We report on a newborn girl with duplication of 18q12.2-->18qter and deficiency of 18p11.2-->18pter which resulted from meiotic recombination of the maternal pericentric inversion, inv(18)(p11.2q12.2). Her clinical manifestations were compatible with those of partial trisomy 18q syndrome. We review the previously reported 9 cases in 8 families of rec(18) resulting from recombination of a parental pericentric inversion. PMID- 8209911 TI - Smith-Lemli-Opitz (RSH) syndrome bibliography: 1964-1993. PMID- 8209912 TI - RSH/SLO ("Smith-Lemli-Opitz") syndrome: historical, genetic, and developmental considerations. AB - Thirty years after the publication of Smith et al. [1964: J Pediatr 64:210-217] of 3(4) cases of the RSH/SLO ("Smith-Lemli-Opitz") syndrome and after the publication by Roux [1964: Arch Franc Pediatr 21:451-464] on the teratogenic action of Triparanol, a defect of cholesterol metabolism was discovered by Tint and his co-workers in the blood of the patients of Irons and Elias [Irons et al., 1993: Lancet 341:1414]. In this manner, the RSH syndrome has been identified as another metabolic multiple congenital anomalies/mental retardation (MCA/MR) syndrome (prototype Zellweger syndrome) in which deficient cholesterol synthesis must be held responsible for all parts of the syndrome, including blastogenetic and organogenetic malformations, minor anomalies, more or less severe abnormalities of CNS and PNS structure and function, postnatal failure to thrive, and, in some cases, stillbirth or infancy/childhood death. PMID- 8209913 TI - Abnormal cholesterol metabolism in the Smith-Lemli-Opitz syndrome: report of clinical and biochemical findings in four patients and treatment in one patient. AB - We report on four patients with the Smith-Lemli-Opitz (SLO) syndrome who appear to have a defect in cholesterol biosynthesis. The initial results of therapy of one of the patients with cholesterol and bile acids to correct her metabolic abnormalities are described. This finding provides a biochemical marker to help in the diagnosis of this syndrome, may provide insight into the pathogenesis of this disorder, and have therapeutic and prenatal diagnostic implications as well. PMID- 8209914 TI - Nutritional requirements of infants and children with respect to cholesterol and related compounds. AB - Cholesterol is an enigmatic, essential metabolite. Breast milk contains significant quantities of cholesterol, yet human infants thrive on cholesterol free diets. Recommendations to lower serum cholesterol are widespread, yet low serum cholesterol is associated with poorly understood morbidity. Serum cholesterol is increased with diets high in fat, yet dietary cholesterol has relatively little effect on serum concentrations. Smith-Lemli-Opitz syndrome, marked with extremely low serum cholesterol, may serve as a human model for the evaluation of absorption and metabolism of dietary cholesterol. PMID- 8209915 TI - Developmental regulation of the expression of genes encoding proteins involved in cholesterol homeostasis. AB - The developmental patterns of expression of HMG-CoA reductase, farnesyl pyrophosphate synthase, cholesterol 7 alpha-hydroxylase, and LDL receptor were investigated using Northern blotting analysis to quantitate mRNA levels. It was found that HMG-CoA reductase and farnesyl pyrophosphate synthase mRNA levels in brain reached peaks at age 4 days which correlates with the time of peak enzyme activity and the onset of rapid brain growth and myelination. In liver, HMG-CoA reductase and cholesterol 7 alpha-hydroxylase mRNA both rose dramatically at weaning. This is consistent with the concept that de novo synthesized cholesterol is the preferred substrate for cholesterol 7 alpha-hydroxylase and may also be involved in the induction of the enzyme. In testes, HMG-CoA reductase activity was highest at age 21 days and then declined, while LDL receptor mRNA levels rose from age 31 to 120 days. These studies suggest a major role for de novo cholesterol synthesis in developing brain, liver, and testes. PMID- 8209916 TI - RSH/SLO (Smith-Lemli-Opitz) syndrome: designing a high cholesterol diet for the SLO syndrome. AB - A high cholesterol diet has been suggested to help prevent the poor reproductive outcomes found in heterozygote carriers of fetuses affected with the Smith-Lemli Opitz (SLO) syndrome. The theory has also been presented that a high cholesterol medical food may enhance myelination of the central nervous system of the infant and prevent demyelination in the child and adult with SLO. Clinical studies are required to test this hypothesis and to determine the optimal composition of such medical foods. FDA requires proof of efficacy and controls nutrient composition, ingredients, and label claims of medical foods. PMID- 8209918 TI - Smith-Lemli-Opitz syndrome in a female with a de novo, balanced translocation involving 7q32: probable disruption of an SLOS gene. AB - A 3-month-old infant girl had manifestations of the Smith-Lemli-Opitz syndrome (SLOS) including typical positional anomalies of the limbs, apparent Hirschsprung disease, cataracts, ptosis, anteverted nares, cleft of the posterior palate, small tongue, broad maxillary alveolar ridges, and abnormally low serum cholesterol levels. Chromosomal analysis showed a de novo balanced translocation interpreted as 46,XX,t(7;20)(q32.1;q13.2). We hypothesize that the translocation breakpoint in this case interrupts one SLOS allele and that the other allele at the same locus has a more subtle mutation that was inherited from the other parent. This case, as well as cytogenetic observations in other SLOS cases, suggests that SLOS could be due to autosomal recessive mutation at a gene in 7q32. PMID- 8209917 TI - Abnormal bile acids in the Smith-Lemli-Opitz syndrome. AB - The urinary bile acids from four patients with Smith-Lemli-Opitz (SLO) syndrome were analyzed by continuous flow fast atom bombardment mass spectrometry. Two types of abnormalities were noted: (1) a deficiency of normal bile acids (cholenoates) and (2) the presence of abnormal species postulated to be cholenoates and cholestenoates. The finding of abnormal urinary bile acids in children with SLO syndrome led to further investigation of the cholesterol metabolic pathway and to the delineation of a new inborn error of metabolism, deficient conversion of 7-dehydrocholesterol to cholesterol [Irons et al., 1993]. The abnormalities of urinary bile acids, if confirmed by further structural analyses and studies of additional patients, provide an explanation for various aspects of the gastro-intestinal abnormalities and growth retardation noted in SLO syndrome and suggest that exogenous bile acid replacement may play an important role in the therapy of patients with this syndrome. PMID- 8209919 TI - Smith-Lemli-Opitz syndrome: biochemical before clinical diagnosis; early dietary management. AB - Pursuit of a possible metabolic basis for an unrecognized pattern of multiple congenital anomalies in a newborn girl led to the detection of a huge elevation of plasma 7-dehydrocholesterol at age 8 months. The biochemical findings and the evolving clinical picture led to the diagnosis of Smith-Lemli-Opitz syndrome at age 11 months. High cholesterol diet may have improved the rate of developmental progress. PMID- 8209920 TI - Re: Pseudo-trisomy 13 syndrome with upper limb shortness and radial hypoplasia. PMID- 8209921 TI - Oligosymptomatic hypothyroidism presenting as apparent spondyloepiphyseal dysplasia. PMID- 8209922 TI - Radioulnar synostosis in Williams syndrome: a historical overview. PMID- 8209923 TI - Waardenburg syndrome and neural tube defects. PMID- 8209924 TI - Gene for Simpson-Golabi-Behmel syndrome is linked to HPRT in Xq26 in two European families. AB - Linkage analysis was performed in 2 previously described European families segregating for the Simpson-Golabi-Behmel (SGB) syndrome. In both kindreds close linkage without recombination (zmax = 4.45 at theta = 0.00) was observed between the disease locus and the HPRT locus mapped in Xq26. These data are very similar to those (zmax = 7.5 at theta = 0.00) reported recently by others after studying a large Dutch-Canadian kindred with SGB syndrome. Compiled lod scores from the 3 families reach their maximum of 11.95 at recombination fraction of 0.00 with one lod unit support interval of 0.00-0.04. PMID- 8209925 TI - Simpson-Golabi-Behmel syndrome (SGBS) in a female with an X-autosome translocation. PMID- 8209926 TI - Abdominal complications following cardiac surgery. AB - Between 1978 and 1991, 116 of 19,246 patients (0.6%) undergoing cardiac surgery developed abdominal complications (renal/hepatic failure excluded) within 30 days of their cardiac operation. Comparison with a randomly selected control group of 217 patients operated upon over the same period of time was also undertaken. Compared to the control group, the study patients were older (mean age, 63.3 +/- 12.5 years vs 57.5 +/- 21.5 years; P = 0.03), more likely to have a history of alcohol abuse (10% vs 4%; P = 0.03), and more likely to have a previous history of gastrointestinal problems (43% vs 17%; P = 0.0001). There was also a trend towards a greater number of patients having valvular surgery, particularly reoperative surgery, in the study group. Postoperatively, patients with marked low cardiac output, requiring the intra-aortic balloon pump, were more likely to develop abdominal complications. These complications included complicated peptic ulcer disease in 54 (47%), intestinal obstruction and/or perforation in 19 (16%), biliary tract disease in 13 (11%), mesenteric ischemia in 13 (11%), acute pancreatitis in 3 (3%), and miscellaneous complications in the remaining 14 (12%). Forty-three patients were treated medically and 73 patients required operative intervention. The surgical procedures performed were truncal vagotomy and drainage (12), oversewing of a perforation or a bleeding vessel (6), gastrectomy (2), intestinal resection (14), laparotomy only (14), cholecystectomy (14), and other (11). Mortality was 26% (30/116) with the mortality for medical and surgical treatment being 16% vs 32%, respectively (P = 0.112). Intestinal ischemia had the highest mortality, with a rate of 85% (11/13). Despite intensive monitoring and care of cardiac surgical patients, abdominal complications do occur, although rarely. Risk factors include older age, a positive history of gastrointestinal disease, reoperative valve surgery, and severe postoperative low cardiac output. PMID- 8209927 TI - Prospectively evaluating anal sphincter function after ileal pouch-anal canal anastomosis. AB - The decreased anal sphincter pressure that occurs after ileal pouch-anal canal anastomosis (IPAA) has usually been attributed to damage of the internal and sphincter. We hypothesized that the operation damages both the internal and the external anal sphincter. Resting pressure in the anal canal (a function of internal and external sphincters), anal squeeze pressure (a function of external sphincter only), and the rectal-anal inhibitory reflex (involving the internal sphincter) were measured manometrically in 10 patients with ulcerative colitis (4 women and 6 men; mean age, 33 years; range: 20 to 49 years). The patients were studied while awake before IPAA, under general anesthesia with striated muscle blockade just before incision, awake 2 months later before ileostomy takedown, and again under anesthesia with blockade just before takedown. The operation decreased maximum resting anal pressure while awake and during anesthesia with blockade. The decrease was detected in the proximal anal canal but not in the distal anal canal. In addition, the operation impaired anal squeeze pressure and abolished the rectal-anal inhibitory reflex. We conclude that IPAA damages both the internal and the external anal sphincter. PMID- 8209928 TI - Acute diverticulitis under age forty. AB - Acute diverticulitis in the young is increasingly common and is not confined to a particular ethnic or socioeconomic group. The majority of cases are in men and occur in the fourth decade of life. Obesity is the major comorbid condition. The disease appears to be an early manifestation of that seen in the elderly based on identical anatomy and histology. The high incidence of surgical intervention and the high incidence of emergent or urgent intervention, particularly following the initial attack, suggests that this manifestation is a more virulent form of the disease. Because of this, any patient under age 40 should undergo resection following the first documented attack of acute diverticulitis. PMID- 8209929 TI - Leukotriene C4 regulation of splanchnic blood flow during ischemia. AB - The role of endogenous splanchnic eicosanoids in mediating splanchnic vasoconstriction induced by the leukotriene C4 (LTC4) was examined during mild hemorrhage/reperfusion injury. Male Sprague-Dawley rats were anesthetized and subjected to sham or acute hemorrhage for 30 minutes, to 30 mm Hg, followed by blood reperfusion (SK+R). The superior mesenteric artery was cannulated and removed with its end-organ intestine (SV+SI preparation) and perfused in vitro with oxygenated Krebs-Henseleit buffer. Perfusion pressure was constantly recorded. Net SV+SI release of 6-keto-PGF1 alpha, PGE2 and thromboxane B2 were analyzed by enzyme immunoassay after LTC4 stimulation. Leukotriene C4 increased perfusion pressure and decreased the ratio of 6-keto-PGF1 alpha to thromboxane release (but not PGE2 to thromboxane B2) in the sham group. Hemorrhage/reperfusion increased perfusion pressure and decreased the ratio of 6 keto-PGF1 alpha to thromboxane B2. Mild hemorrhage/reperfusion increased LTC4 induced splanchnic vasoconstriction in part by decreasing the release ratio of endogenous splanchnic PGI2 to thromboxane B2. PMID- 8209930 TI - Peptide YY augments postprandial small intestinal absorption in the conscious dog. AB - Since feeding increases intestinal fluid and electrolyte losses in short bowel syndrome, an agent increasing postprandial small bowel absorption might have a therapeutic role. Peptide YY (PYY) has recently been shown to increase net small bowel absorption under basal conditions. The aim of this study was to determine whether PYY can also augment postprandial absorption. Exteriorized, neurovascularly intact jejunal and ileal segments (25 cm Thiry-Vella loops) were created in dogs (n = 6) and gastrointestinal continuity was restored. Luminal perfusion with [14C]polyethylene glycol was used to calculate the change in water (H2O) and sodium (Na+) and chlorine (Cl-) ion fluxes after an oral meal. Changes in fluxes were also determined after a 2-hour infusion of a physiological dose of PYY (100 pmol/kg per hour). In a third series of experiments, fluxes were measured after a meal, during PYY infusion. Feeding increased small bowel absorption of fluid and electrolytes independent of the luminal content. This effect persisted for 2 hours after the meal. PYY infusion significantly augmented this proabsorptive response in both jejunum and ileum. These results suggest that PYY-agonists may have a therapeutic role in conditions such as short bowel syndrome where postprandial absorption is reduced. PMID- 8209931 TI - Serum D(-)-lactate levels as an aid to diagnosing acute intestinal ischemia. AB - No serum marker has consistently proved helpful in diagnosing early acute mesenteric ischemia. D(-)-lactate is a product of bacterial metabolism and was found to be elevated in peripheral blood in a rat model of intestinal ischemia. We conducted a prospective study to evaluate preoperative D(-)-lactate levels in 31 patients undergoing laparotomy for acute abdominal emergencies, including suspected acute mesenteric ischemia. The serum was deproteinated and D(-)-lactate concentration was determined by a spectrophotometric assay. A control group was composed of patients with a benign abdominal examination who were operated on for central venous line placement. We found significant elevations in D(-)-lactate levels in patients with mesenteric ischemia compared with controls (P < 0.00005), as well as in patients with other forms of abdominal catastrophes (P < 0.00005) and with bowel obstruction (P < 0.0005). Sensitivity and specificity were 90% and 87%, respectively. The negative predictive value was 96%, and the positive predictive value was 70%. We have found that D(-)-lactate serum levels can aid in diagnosing acute mesenteric ischemia. PMID- 8209932 TI - Induction of chronic graft-versus-host disease in a rat model after transplantation of sensitized small bowel allografts. AB - The recent success in controlling acute rejection in clinical small bowel transplantation has resulted in a number of patients with functioning grafts and an occasional occurrence of graft-versus-host disease (GVHD). To better understand this complication following small bowel transplantation, a model of chronic GVHD was developed, using the Brown Norway-->Lewis rat strain combination. When the Lewis recipients were immunocompromised at the time of transplantation and received a graft specifically sensitized against Lewis, fatal GVHD developed in 3 of 5 animals. Serial histologic evaluation and determination of donor major histocompatibility complex (MHC) class I antigens were used to delineate the course of GVHD. Although the histologic results were inconsistent, with the exception of the animals developing fatal GVHD, the detection of donor MHC antigens correlated well with the development of GVHD. Determination of donor MHC class I antigens may serve as useful indicators for the development of GVHD. PMID- 8209933 TI - Diagnosing intestinal ischemia using a noncontact superconducting quantum interference device. AB - Intestinal ischemia is associated with changes of the basic electric rhythm (BER) of the small intestine. We hypothesized that these changes can be measured noninvasively using a superconducting quantum interference device (SQUID). After general anesthesia, a laparotomy was performed on 10 animals and the jejunum was placed in a nonmagnetic recording chamber containing Krebs' solution at 38 degrees C. Five animals had electrodes placed while five others were placed under the SQUID. Injection of thrombin into the mesenteric artery decreased blood flow (measured with a laser doppler flow-meter) 95% within 5 minutes. SQUID measurements showed significant decreases (P < 0.01 for all changes) in the frequency (15.5 +/- 0.3 to 8.9 +/- 0.2 cycles/min) and the propagation velocity of slow waves (3.5 +/- 0.2 to 1.9 +/- 0.3 sec). The changes in intestinal biomagnetic activity after ischemia were similar to the changes in electrical activity. The SQUID magnetometer is a reliable noncontact device that can detect early intestinal ischemia in animal models. We have recently recorded human small bowel biomagnetic activity using a SQUID magnetometer and believe further technical developments will permit the noninvasive diagnosis of mesenteric ischemia. PMID- 8209934 TI - The role of abdominal drainage after major hepatic resection. AB - The authors reviewed their recent experience with major hepatic resection in order to evaluate the role of abdominal drainage in the development and treatment of postoperative complications. Fifty-one patients underwent major hepatectomy with abdominal drainage; 44 of these patients (86%) for malignancy (average age at operation: 59 years). Drains were removed after a median period of 4 days. Major complications occurred in 16 patients (31%), and 3 patients (6%) had a fatal outcome. Twenty patients (39%) experienced minor complications, including 6 cases (12%) of ascitic leak from the insertion site. Considering the type and extent of liver resections reported in this series, these results suggest that abdominal drainage, if technically adequate and maintained for a short period, is not responsible for a high rate of postoperative complications. Its use, although questionable after limited resections, is, therefore, still recommended after difficult and extended hepatectomies. PMID- 8209935 TI - Ten-year follow-up of a prospective, randomized trial of selective proximal vagotomy with ulcer excision and partial gastrectomy with gastroduodenostomy for treating corporeal gastric ulcer. AB - Between 1975 and 1980, 30 patients with type I corporeal gastric ulcer were randomly allocated to undergo selective proximal vagotomy with ulcer excision or partial gastrectomy with gastroduodenostomy. Sixteen patients underwent selective proximal vagotomy (1 was excluded from the follow-up since microscopic examination of the excised ulcer revealed an early gastric cancer) and 14 underwent partial gastrectomy. No significant differences in the clinical results were found 3 years after surgery. During a median follow-up of 10 years, ulcer recurred in 3 patients after selective proximal vagotomy and in 2 after partial gastrectomy. One patient in each group had recurrent ulcer without symptoms and received no treatment. Two selective proximal vagotomy patients and three partial gastrectomy patients had epigastric pain with or without ulcer. One patient with selective proximal vagotomy underwent a second operation because of epigastric pain and recurrent ulcer. Bowel habits remained unchanged in all but one patient in each group, and mild or moderate dumping was recorded for two patients in each group. Very good or good results (modified Visick scale) were recorded for 11 of 15 patients after selective proximal vagotomy and for 10 of 14 patients after partial gastrectomy. Except for one patient in each group who had moderate dumping, patients classified as Visick III or IV had no symptoms during treatment with antacids or H2-blockers, or had asymptomatic ulcers and needed no treatment. Selective proximal vagotomy reduced the median acid response to insulin hypoglycemia and to pentagastrin by 100% and 80%, respectively, for at least 3 to 5 years, and partial gastrectomy reduced the median acid response to pentagastrin by 97%. In our opinion, selective proximal vagotomy with ulcer excision is an alternative to partial gastrectomy for surgically treating type I gastric ulcer. PMID- 8209936 TI - Electrocautery used to create incisions does not increase wound infection rates. AB - A prospective, randomized, blinded clinical trial was conducted to determine whether electrocautery as a means of creating abdominal or thoracic wounds would result in increased wound infection rates. Over a 15-month period, 492 consecutively studied patients were randomly placed into 1 of 2 groups: scalpel or electrocautery. There were no differences in age grouping, use of steroids, incidence of diabetes, number of days preoperative, operative time, use of preoperative antibiotic prophylaxis, use of drains, number of obese patients, or gender ratio. Wound infections developed in 38 of the 250 scalpel patients (15%) and in 30 of the 242 cautery patients (12%). The use of electrocautery to create surgical wounds does not increase wound infection rates. PMID- 8209937 TI - A pilot experience with competency-based clinical skills assessment in a surgical clerkship. AB - This investigation examines a competency-based clinical skills assessment program for surgical clerks using checklists and rating forms for precise measurement of physical exam (PE) skills, physician-patient interaction (PPI) skills, and patient write-up (PW) skills. Analysis of variance demonstrated improvement in PW skills across the academic year when measured by the rating instrument, but this improvement was not detected on traditional subjective rating forms (SRF). PPI skills improved between first rotations across 2 academic years with the addition of orientation to expectations (mean, 79% versus 92%, P = 0.000). Poor correlation was noted between the National Board of Medical Examiners Surgery Subtest scores and PE skills (r = .19), PW skills (r = .20), and PPI skills (r = .15). While the overall ratings given by faculty on SRF correlated with the SRF ratings of PE skills (r = .77) and PPI skills (r = .58), these same faculty ratings correlated poorly with these skills as assessed by checklist (r = .16 and r = .14, respectively). This pilot experience demonstrates that PE skills, PW skills, and PPI skills (1) improve only with orientation to expectations and feedback, (2) correlate poorly with fund of knowledge assessment, and (3) are best assessed with precise measurement (eg, checklist, direct observation), which avoids the halo effect of overall evaluation that occurs with subjective rating forms. PMID- 8209938 TI - The need to retrieve the dropped stone during laparoscopic cholecystectomy. AB - The effect of bile and gallstones on the peritoneal cavity was evaluated in an experimental animal study. Ninety male Sprague-Dawley rats were randomly allocated to one of six groups (n = 15). Groups 1 to 3 received an intraperitoneal injection (2 mL) of saline, sterile bile, and infected bile, respectively. Groups 4 to 6 underwent a lower midline abdominal incision (3 to 5 mm). In groups 4 and 5, a single gallstone (< 3 mm diameter) was placed in the right upper quadrant and, after closure of the wound, the animals were injected with sterile bile and infected bile, respectively. Group 6 animals underwent laparotomy alone, followed by injection of sterile saline (2 mm). All animals were killed at 4 weeks and the peritoneal cavity was carefully examined. No intra abdominal lesions were noted in groups 1 to 3. Adhesions were noted in 11 (73%) and 10 (67%) animals of groups 4 and 5, respectively. Two intra-abdominal abscesses were noted in group 4 animals. No intra-abdominal lesions were noted in any group 6 animals. This study suggests that bile in combination with gallstones in the peritoneal cavity is associated with an increased risk of intra-abdominal adhesion formation and possible abscess formation, and that every attempt should be made to retrieve stones lost during cholecystectomy. PMID- 8209939 TI - Laparoscopic splenectomy. AB - A technique for laparoscopic splenectomy is described. The patient is placed in the right semidecubitus position and pneumoperitoneum is prepared. The splenic artery and vein are exposed near the hilum, using a laparoscopic ultrasonic dissector. The larger vessels are doubly ligated, and the spleen is resected and maneuvered into a nylon surgical sack; the sack is removed through a 2-cm incision along the midaxillary line. This procedure has been used for four patients requiring splenectomy for benign disease, and the outcome has been entirely satisfactory for all concerned. PMID- 8209940 TI - The brachioaxillary interposition graft as a successful tertiary vascular access procedure for hemodialysis. AB - There is a steady increase in the number of patients with chronic renal insufficiency undergoing long-term hemodialysis, and an increasing number of these patients have exhausted veins due to multiple vascular access and salvage procedures. These patients may be candidates for an alternative vascular access procedure, the brachioaxillary interposition arteriovenous graft. This graft was used in 13 patients with a 100% patency rate and no significant complications at 81 patient months. The results indicate that the large axillary vein, which provides an adequate runoff, and a narrow graft-to-vein inflow angle may lessen the turbulence inherent in the more conventional grafts and may contribute to an improved long-term patency. If these assumptions prove correct, this graft may find more frequent application in the future. PMID- 8209941 TI - Patient- and treatment-related factors associated with acute regional toxicity after isolated perfusion for melanoma of the extremities. AB - In order to gain some insight into the cause of acute regional toxicity after isolated perfusion using melphalan, 15 patient-related and perfusion-technique related factors were tested in a logistic regression model. Acute toxicity was graded according to Wieberdink's grading system. In a group of 425 patients, 362 (85%) encountered no or slight toxicity with a grade I or II reaction, and 63 (15%) patients encountered more severe toxicity with a grade III, IV, or V reaction. Most patients were treated with a standard dose of 10 or 13 mg melphalan per liter of perfused tissue for leg and arm perfusions, respectively. Factors associated with a more severe toxicity reaction proved to be tissue temperatures of 40 degrees C or higher, female gender, a deterioration of the gas values of the venous perfusate during perfusion, and perfusion at a proximal level of isolation. Consideration of these prognostic factors may lead to a further decrease of acute regional toxicity in perfusion. PMID- 8209942 TI - Local recurrence differs from local persistence. PMID- 8209943 TI - Scoring systems for prediction of mortality in critical trauma. PMID- 8209944 TI - [Polycystic ovaries]. PMID- 8209945 TI - [Prostaglandin content in decidual tissue of women in spontaneous abortion]. AB - Prostaglandins E2 and F2 alpha were measured in decidual tissue of women after spontaneous abortions at pregnancy terms 8 to 10 weeks and after abortions induced by sulprostone, a synthetic prostaglandin E2 analog, at pregnancy term 4 5 weeks. Women in whom pregnancy was terminated surgically at relevant periods were controls. Prostaglandin E2 concentration was found to be 5 times higher and that of prostaglandin F2 alpha 40 times higher in women with spontaneous abortions than in surgical abortion. In sulprostone-induced abortion prostaglandin concentrations in decidual tissue were the same as in controls. These data indicate that a drastic increase of prostaglandin levels in spontaneous abortion is not only a result of myometrial contractions or decidual tissue rejection, but an important component in the chain of events leading to miscarriage. PMID- 8209946 TI - [Management strategy for pregnant women with portal hypertension syndrome]. AB - The authors describe their management policy with pregnant patients suffering from portal hypertension syndrome, based on the results of comprehensive examinations and deliveries in 44 women. Principal indications for abortions in such patients are active liver cirrhosis, third-degree varicosity of esophageal and gastric veins, dilatation of the esophagus. Natural labor is permitted when there are no threatened bleedings. Therapy is administered in accordance with obstetrical indications. In case esophagogastric bleedings develop emergency measures to arrest the bleeding are taken, rapid delivery and, if necessary, emergency surgical intervention. Knowledge of risk factors helps the problem of pregnancy maintenance and delivery mode to be solved by obstetricians and specialists in portal hypertension. This management policy promoted successful deliveries in 42 of 44 cases. PMID- 8209947 TI - [Experimental validation of the efficacy of laser-magnetic therapy for chronic placental insufficiency]. AB - A new pathogenetically based non-medicamentous method for correction of uteroplacental bloodflow disturbances has been developed on the model of chronic placental insufficiency in rats. A single 5 min laser-magnetic exposure on day 21 of normal pregnancy resulted in a vasodilating effect with reduction of the peripheral resistance in the uterine horn vessels and with improvement of their blood supply. A new LAMA laser magneto-therapeutic device was employed. Daily 5 min sessions of laser magnetic therapy administered to rats with chronic placental insufficiency from pregnancy days 15-16 to 21 normalized uterine horn contractility and resulted in positive morphofunctional changes in the components of the uterine horns and placenta, being associated with a noticeable improvement of fetal functions. Hence, laser magnetic therapy may be regarded as an effective non-drug method for therapy of chronic placental insufficiency. PMID- 8209948 TI - [Methods for obtaining fetal blood and its characterization]. AB - Fetal blood was collected in 83 women, 71 of these before abortions and in 12 of them with diagnostic purpose. Cardiocentesis was used in 31 cases, cordocentesis in 52. Obstetrical situation was analyzed and fetal heart beat recorded during the procedure. Blood group and rhesus appurtenance were determined in blood samples, Kleinhauer-Batke test was carried out, karyotype, HLA phenotype, and DNA analyzed. A positive result was found dependent on the adequate assessment of an obstetrical situation during fetal blood collection, as well as on equipment resolution power and physicians' experience. The possibility of practical use of cordo- and cardiocentesis is discussed with due consideration for these factors. PMID- 8209949 TI - [A method of single-row repair of the lower segment of the uterus during Cesarean section]. AB - The authors describe the technique and share their experience gained in repair of the lower segment of the uterus during cesarean section with a single-row suture. The incidence of postoperative complications was markedly reduced after such an operation, severe complications were not recorded, and the incidence of spontaneous deliveries after repeated pregnancies increased. PMID- 8209950 TI - [Pregnancy-associated alpha2-glycoprotein and trophoblastic beta1-glycoprotein in the diagnosis of pyoinflammatory diseases after Cesarean section]. AB - Blood serum pregnancy-associated alpha 2-glycoprotein and trophoblastic beta 1 glycoprotein were measured in puerperants with the normal postpartum period and with that complicated by pyo-inflammatory diseases after abdominal delivery. The levels of both proteins were found reduced in the patients with pyo-inflammatory diseases developing after cesarean section as early as on day 1 postpartum. that of alpha 2-glycoprotein by 1.2 times, that of trophoblastic beta 1-glycoprotein twofold. PMID- 8209951 TI - [Maternal and neonatal health]. PMID- 8209952 TI - [Prevention of postpartum inflammatory diseases in puerperae with pyelonephritis and toxemia]. AB - Puerperae with acute and chronic pyelonephritis complicated by gestosis often develop postpartum inflammatory complications in the presence of marked deficiency of T lymphocytes and phagocytic function. Clinical criteria are suggested to single out risk groups. Prophylactic injections of leukinferon (alpha-interferon) and other immune response first phase cytokines in complex with metabolic agents help almost normalize the immunologic parameters in the majority of puerperae within 3-6 days and reduce threefold the incidence of early and late postpartum inflammatory complications. PMID- 8209953 TI - [Autonomic nervous system activity during the normal menstrual cycle]. AB - Body adaptation reactions to changes of the internal conditions (neurohumoral shifts related to ovulation and corpus luteum development) were studied in 15 women of a reproductive age with normal biphasic cycle in the early follicular and medium lutein phases on the basis of mathematical analysis of heart rhythm, a number of cardiovascular and respiratory system parameters, and brain electric activity. Moderate tension of the regulatory mechanisms in the lutein phase of the cycle was protective and adaptive and probably related to body preparation to a would-be pregnancy. These adaptive effects are different in different women: in some internal environment parameters vary within a wide spectrum, in others these parameters show a trend to retain their functioning regimen. PMID- 8209954 TI - [Functional state of the reproductive system in patients with the hypogonadotropic form of amenorrhea during use of various protocols of ovulation induction with human menopausal gonadotropins]. AB - Clinico-hormonal parameters of cycles stimulated with human menopausal gonadotropins in patients with hypogonadotropic amenorrhea and of spontaneous cycles in healthy women of reproductive age are compared. Estradiol hypersecretion in both phases of induced cycle was revealed: hydrocortisone in phase 1 and progesterone and testosterone in phase 2. Dexamethasone in daily dose 0.25 mg was administered for correction. This resulted in a noticeable reduction of estradiol hyperproduction in the first phase of stimulated cycles and in hyperandrogenism elimination. Folliculogenesis, ovulation, and early embryogenesis conditions in schemes of induction with human menopausal gonadotropins and dexamethasone therapy were close to physiologic ones, this resulting in increased share of fertile cycles. PMID- 8209955 TI - [Endometrial and ovarian morphology in internal uterine endometriosis]. AB - The ovaries and endometrium were examined in 66 patients with internal uterine endometriosis with various degrees of the process dissemination. A high incidence of combinations of uterine endometriosis with hyperplastic processes in the ovaries was revealed (72.7%) and a relatively low incidence of uterine body mucosa involvement (31.7%). The degree of endometriosis dissemination in the myometrium and the incidence of ovarian hyperplasia were in direct proportion. The authors emphasize the usefulness of morphologic studies of the ovaries in patients with internal uterine endometriosis. PMID- 8209956 TI - [Change in phospholipid content in platelets, immunocompetent cells and myometrial tissue in patients with internal endometriosis]. AB - A method of flow horizontal chromatography has been developed permitting investigation of blood and tissue cellular phospholipids ruling out lipid peroxidation effects on cellular membranes. Phospholipid levels of blood and myometrial tissue cells were measured by this method in 67 patients with histologically verified internal endometriosis. Phospholipid and phosphatidyl inosite levels in platelets and immunocompetent cells of these patients reliably differed from those in healthy women. Phosphatidyl inosite levels of heterotopic endometrial tissue was increased by 1.4 times vs. the norm on an average. In parallel with this, a reliable change of phosphatidyl cholines and inosites levels in endometriosis foci were detected as against their levels in intact tissue. The authors suggest a method for the diagnosis of internal endometriosis by phosphatidyl inosite levels in blood lymphocytes. PMID- 8209957 TI - [Possible approaches to improvement of the efficacy of health resort treatment of women with pelvic inflammatory diseases]. AB - Hydrogen sulfide balneotherapy paralleled with thymogen (an immunocorrector) therapy improved clinical and immunologic characteristics, ruled out disease recurrences and exacerbations during 12 months after the treatment, and increased the number of pregnancies by 2.5 times in infertile patients. PMID- 8209958 TI - [Strategy and results of restorative surgery in urinary tract injuries in obstetric and gynecology practice]. AB - The author analyzes the causes and types of intraoperative injuries to the urinary tract and the results of surgical repair in 10 patients exposed to various interventions on the uterus and the tubes. He advocates single-stage reconstructive repair in patients with acute injuries to the ureters which were not recognized in time. Immediate and late results of treatment were good in all the patients operated on. PMID- 8209959 TI - [Assessment of the diagnostic value of fetal biophysical profile in multiparous women]. PMID- 8209961 TI - [Prostaglandins in obstetrics]. PMID- 8209960 TI - [Aleksandr Matveevich Makeev, professor emeritus, philanthropist]. PMID- 8209962 TI - [Female reproductive function in thyroid pathology]. PMID- 8209963 TI - [Non-Hodgkin lymphoma of the maxillary sinus]. AB - Non-Hodgkin Lymphoma is an infrequent tumor at the paranasal sinuses site, representing no more than 5.8 to 8 percent of the entire malignant neoplasias in this localization. Clinical manifestations are insignificant and the definitive diagnosis comes through its pathological study. Treatment is fundamentally radiotherapy, either isolated or in association to polychemotherapy. Its prognosis use to be better than that of those lymphomas arising in Waldeyer's area. In this paper a case of a primary lymphoma of the maxillary antrum is reported and the literature about this condition is reviewed. PMID- 8209964 TI - [Maxillary mucocele. Report and consideration of one case]. AB - An outpatient 24 years-old, with an antral mucocele is presented. Mucocele's pathogenesis of this morbid process is revised. PMID- 8209965 TI - [Magnetic resonance applied to the diagnosis of Sjogren disease]. AB - In order to characterize typical MRI-findings in patients with Sjogren's syndrome who present recurrent parotid swelling 15 patients with clinical diagnosis of this disease were examined in a prospectives study. Most of the patients showed bilateral enlarged glands with an inhomogeneous, nodular pattern. The signal intensity was very high, especially in the T2 weighted sequences. PMID- 8209966 TI - [Aggressive fibromatosis of the nasal sinuses]. AB - A case report of a feminine patient who complained of nasal ventilatory obstruction and nasosinusal polyposis is presented. She underwent surgery and the pathological study revealed the existence of an aggressive fibromatosis. The AA. review the literature dealing with this illness and explain an update state of the clinical features, treatment and the course of this rare entity, closely related to fibrosarcoma. PMID- 8209967 TI - [Interactive morphometry and densitometry for the study of epidermoid carcinoma of the larynx. Preliminary results]. AB - At present the utilization of quantitative techniques in anatomopathological studies is becoming more and more frequent, so adding the possibility of gaining measures and numerical assessments in front of conventional quantitative evaluations. In the paper the AA. report their first attempt with conventional slides of epidermoid carcinomas of the larynx, taken from the files. The aim has been to check out the contribution of this procedure compared with other traditional pathological techniques. PMID- 8209968 TI - [Distress of the airway due to vertebral ankylosing hyperostosis or Forestier Rotes' disease]. AB - The AA. present one case in which the air-way was severely compromised because of the causative vertebral ankylosing hyperostosis, the so-called Forestier-Rotes's malady. Only 7 of resembling cases are recorded in the consulted literature. Survey of the related bibliography and comments about pathogenic criteria and diagnostic and therapeutic questions as well. PMID- 8209969 TI - [Pseudosarcoma of the larynx]. AB - Paper dealing with 3 cases of laryngeal Pseudosarcoma diagnosed and treated recently (in the last 6 years) at the AA's Department. Discussion about the histogenesis of these growths which components are epithelial and sarcomatous tissues. Survey of the bibliography of the subject. PMID- 8209970 TI - [The use of implanted devices for the central venous access in ENT. Placement and aftercare]. AB - Implantable venous access system's utility in ENT is reviewed. The implantation's technique and their management are commented. PMID- 8209971 TI - [Adenocarcinoma of the nasal cavities and paranasal sinuses. On low-grade adenocarcinoma]. AB - The AA. having had the opportunity to diagnose and treat one of those cases, of low degree, sitting in the nasal cavity, discuss about its classification either in the nose or in the sinuses. Their opinion is coincidental with that of other reporters regarding to the complexity and varieties of a grouping system. They propose an other one, not original at all, but having perhaps the advantage that could make easier the comprehension and the clinical orientation when dealing with these growths. PMID- 8209972 TI - [Verification of desferrioxamine ototoxicity by high-frequency audiometry in patients undergoing dialysis]. AB - The AA. have studied the Desferrioxamine ototoxicity with high frequency audiometry (HFA), given the drug as a test for diagnosis of aluminium-related done disease in patients under dialysis. The dose of 10 mg/kg presents high sensitivity and low ototoxicity. PMID- 8209973 TI - Diagnosing malignant hyperthermia susceptibility. PMID- 8209974 TI - Basic simulations for anaesthetists. A pilot study of the ACCESS system. AB - This paper describes the design and initial testing of the ACCESS (Anaesthetic Computer Controlled Emergency Situation Simulator) system, which has been designed to simulate anaesthetic emergencies with the aim of providing training for junior doctors. The simulations require little or no capital expenditure with minimal use of time by staff or trainees. They are based on standard anaesthetic equipment, with a microcomputer providing an image of commonly used instruments. Problems are presented as scenarios administered by the teacher, and test the skills of the pupil. During 64 scenarios, five trainees caused two 'deaths' and solved the problems in a median time of 2.5 min, while an experienced group of anaesthetists caused one 'death' and took 1.8 min. The simulation was rated by the pupils as easy to use, realistic and a valuable educational tool. PMID- 8209975 TI - Effects of background stress and anxiety on postoperative recovery. AB - The effects of background stress and anxiety on both short- and long-term recovery were measured in 30 healthy patients undergoing general anaesthesia for day-case dental extractions. Standardised questionnaires presented pre operatively, assessed psychological status in terms of trait and state anxiety and stress levels. State anxiety was again measured postoperatively; recovery was assessed with pre- and postoperative batteries of cognitive tasks. Correlation coefficients revealed that the level of background stress in the preceding 6 months correlated with physical parameters of recovery such as time taken for patients to open their eyes, perceived pain and increased postoperative morbidity. The study also demonstrated that high levels of state anxiety after surgery correlated with postoperative pain. Trait and state anxiety before surgery did not correlate with any parameters of recovery or postoperative morbidity. PMID- 8209976 TI - Brainstem auditory evoked response changes following electro-acupuncture therapy in chronic pain patients. AB - Brainstem auditory evoked responses were recorded in 17 patients with chronic pain who had been given electro-acupuncture therapy. The absolute peak latencies of waves I to V, and interpeak latencies and amplitudes of waves I and V were analysed before electro-acupuncture and compared with values obtained during electro-acupuncture and 5 min after its termination after one, five and 10 sittings. At these sittings the intensity of pain was recorded with the help of a 100 mm visual analogue scale. Each patient had 10 sittings given on alternate days. The absolute peak latencies of waves I, II, and III were delayed significantly (p < 0.05) after 5 and 10 sittings and amplitudes of wave V decreased significantly (p < 0.05) after 5 and 10 sittings. Visual analogue scores also decreased significantly (p < 0.01) during these sittings. It was established that before and after 10 sittings of electro-acupuncture, there was a significant positive correlation between visual analogue scores and the amplitude of wave V (p < 0.01). There was a negative correlation between visual analogue scores and absolute peak latencies of wave III at 1, 5 and 10 sittings, suggesting that there is a definite interaction between the electro-acupuncture neural mechanism and the generators of brainstem auditory evoked responses in the lower brainstem. PMID- 8209977 TI - Effect of weaning on oxygen consumption and cardiovascular function. A comparison of continuous flow and demand valve systems. AB - This study compared the continuous positive airways pressure mode of the demand valve system of the Engstrom Erica ventilator with a custom-made continuous flow continuous positive airways pressure system in terms of the oxygen cost of breathing during weaning from mechanical ventilation. Ten consecutive patients in our intensive care unit, with thermodilution pulmonary artery flotation catheters in situ, were studied. Measurements were carried out under steady-state conditions, initially when breathing spontaneously with continuous positive airways pressure via the Erica and then when transition to the continuous flow system was achieved. There were no significant differences between the two methods of providing continuous positive airways pressure in terms of the measured and derived physiological variables studied, with the exception of oxygen consumption. Oxygen consumption with the continuous flow system was significantly less than with the Erica (142.8 (SEM 31.4) ml.min-1.m-2 compared with 165.8 (SEM 30.5) ml.min-1.m-2, p < 0.05). This difference reflects the reduced oxygen cost of breathing when the custom-made continuous flow system was used during weaning. PMID- 8209978 TI - Conjunctival oxygen tension monitoring during liver transplantation. AB - Conjunctival oxygen tension has been noted in animal studies to correlate with oxygen delivery. In order to assess this relationship in man, we compared the proportional changes in conjunctival oxygen tension with those in oxygen delivery that occur on the placement and release of the inferior vena caval clamps in 10 patients during orthotopic liver transplantation without veno-venous bypass. We also examined the changes in mixed venous oxygen saturation at these times. We found a statistically significant correlation between both parameters and oxygen delivery (p < 0.001). However, analysing the data on a Bland and Altman plot of difference versus mean, it is our conclusion that the variation in the data is such that neither conjunctival oxygen tension nor mixed venous oxygen saturation can be used clinically to predict the changes in oxygen delivery that occur during liver transplantation. PMID- 8209979 TI - A new method of veno-venous bypass during human orthotopic liver transplantation. AB - Veno-venous bypass is commonly used during orthotopic liver transplantation, but there is some controversy as to whether it contributes to a better outcome. Low shunt flows frequently reduce the efficacy of portofemoro-axillary systems and so a percutaneous cannulation technique for the subclavian and femoral vein with large bore catheters was developed in order to facilitate bypass management. This study reports the performance and complications of a portofemoro-subclavian bypass system during the anhepatic phase of human orthotopic liver transplantation in 85 patients. A percutaneous cannulation technique and two 7 mm (subclavian and femoral) catheters, inserted pre-operatively, were used in a pump driven portofemoro-subclavian bypass system. Coagulation profiles, shunt flows, haemodynamic parameters, and peri-operative complications associated with bypass were recorded for each patient. Percutaneous cannulation of the left femoral and subclavian vein was successful in 78 patients (91.8%). Mean femoro-subclavian shunt flow was 1.45 l.min-1 (SD 0.37), and mean portofemoro-subclavian flow was 4.28 l.min-1 (SD 1.03). Although oxygen delivery was not maintained at pre-shunt levels (559.7 (SD 147) vs 506 (SD 107) ml.min-1.m-2, p < 0.05) renal perfusion pressure stayed above 50 mmHg (during shunt it was 56 (SD 9) mmHg). One intra operative air embolism was observed (1.2%), and in one patient a myocardial infarction occurred during the anhepatic phase; neither complication was considered to be related to the percutaneous cannulation technique. There were no bleeding complications. After operation, all chest X rays were normal and clinical examination revealed no adverse effects of portofemoro-subclavian bypass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209980 TI - Hypomagnesaemia, cardiac arrhythmias and orthotopic liver transplantation. AB - Two patients who underwent orthotopic liver transplantation and developed peroperative cardiac arrhythmias are presented. In one, the arrhythmias were refractory to treatment with anti-arrhythmic drug therapy until serum magnesium levels were restored to normal. The other patient had a low pre-operative serum magnesium level and developed atrial fibrillation on induction of, and during, anaesthesia. Patients undergoing orthotopic liver transplantation may be a group especially predisposed to hypomagnesaemia. The importance of monitoring serum magnesium levels in such patients who develop peroperative cardiac arrhythmias is emphasised. PMID- 8209981 TI - Anaesthesia for caesarean section in a patient receiving high dose amiodarone for fetal supraventricular tachycardia. AB - We report the anaesthetic management of a Caesarean section in a woman treated with high dose amiodarone for fetal supraventricular tachycardia. Most of the interactions between anaesthesia and amiodarone therapy previously reported were observed during general anaesthesia. We therefore chose epidural anaesthesia using incremental doses of lignocaine 2% with adrenaline and fentanyl. This technique appeared to be safe, but since severe refractory vasodilation with hypotension may occur, potent vasopressor agents should be immediately available. PMID- 8209982 TI - An unusual complication of Cornelia de Lange syndrome. AB - A previously undescribed complication of Cornelia de Lange syndrome is reported. The patient developed severe chronic pericarditis with subsequent fatal postoperative cardiac tamponade. PMID- 8209983 TI - Emergency X ray-guided nasotracheal intubation in a patient with a spinal epidural haematoma. AB - A patient with a spinal epidural haematoma who developed tetraparesis and respiratory insufficiency is described. Nasotracheal intubation was successfully and rapidly undertaken with the aid of continuous fluoroscopy. PMID- 8209984 TI - Apparent massive tongue swelling. A complication of orotracheal intubation on the Intensive Care Unit. AB - The trachea of an 81-year-old woman was intubated with an orotracheal tube for emergency abdominal surgery and the tube was left in place for postoperative management on the Intensive Care Unit. After 36 h, she developed apparent massive tongue swelling. On closer examination, a normal sized tongue was found to be displayed by oedema of the floor of the mouth and submandibular space, secondary to purulent sialadenitis from right submandibular duct obstruction by the tracheal tube. PMID- 8209985 TI - Lingual haematoma following treatment with streptokinase and heparin; anaesthetic management. AB - A 79-year-old man with a diagnosis of myocardial infarction treated with streptokinase and heparin developed a large lingual haematoma, precipitating dysphagia and upper airway obstruction. Spontaneous haemorrhage into the tongue is a previously unreported but serious complication of thrombolytic therapy. Tracheal intubation was performed under local anaesthesia. PMID- 8209986 TI - Laboratory assessment of a user-assembled oxygen generation kit. AB - A laboratory assessment was made of a user-assembled oxygen generation kit designed for use in medical emergencies in the community. Twenty-five kits were studied at five different water temperatures and the rate of oxygen generation and its concentration were measured. The apparatus produced a mean (SD) oxygen volume of 37 (1.98) l which was not affected by the starting water temperature. The mean (SD) rate of flow varied from 2.2 (0.04) l.min-1 at 16 degrees C to 10.3 (2.74) l.min-1 at 40 degrees C but the duration of flow varied inversely. Oxygenation concentrations ranging from 30-51% were produced at starting water temperatures from 22 degrees C-40 degrees C, respectively. PMID- 8209987 TI - Sedation for ventilation in the critically ill. A role for isoflurane? PMID- 8209988 TI - Fidel Pages Mirave (1886-1923). The pioneer of lumbar epidural anaesthesia. PMID- 8209989 TI - The effects of dobutamine therapy in critically ill patients measured by transoesophageal echocardiography and intracardiac monitoring. AB - Fourteen patients with severe hypotension and adult respiratory distress syndrome after trauma (n = 7), general surgery (n = 6) or burns (n = 1) were studied. After volume loading with 6 ml.kg-1 hydroxyethyl starch over 30 min (time I), dobutamine was infused intravenously at 5 micrograms.kg-1.min-1 (time II) and 10 micrograms.kg-1.min-1 (time III). A 5 MHz transoesophageal echocardiographic probe was used to image a standard transgastric short axis view of the left ventricle. Haemodynamic data were obtained from thermodilution studies using pulmonary flotation catheterisation. Echocardiographic measurements (off-line from videotape) and qualitative visual assessment of left ventricular function (visual assessment, on-line) were performed. All measurements were made after fluid replacement, and during infusion of the two dobutamine doses. An improvement in mean systemic arterial blood pressure and mean stroke volume occurred from time I to the end of dobutamine infusion (p < 0.05). All patients, after volume infusion, were normovolaemic according to transoesophageal echocardiography and there was a good correlation between end-diastolic area and stroke volume (r = 0.73). During dobutamine infusion, echocardiographic measurements showed no significant dose-related increase in mean (SD) percentage left ventricular short axis area change from baseline after hydroxyethyl starch (time I: 60 (2); time II: 63 (2); time III: 64 (2)). However, a significant increase in short axis area change was seen in nine of the 14 patients (67%). Analysis of the end-diastolic area/short axis area change relationship revealed a heterogeneous response to dobutamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8209990 TI - Effects of the cervical collar on cerebrospinal fluid pressure. AB - We investigated the hypothesis that cervical collars might compress the internal jugular veins and raise intracranial pressure in head-injured patients. In a randomised, single-blind, crossover study of nine patients scheduled for elective spinal anaesthesia the cerebrospinal fluid pressure in the lumbar subarachnoid space was measured with and without a 'Stifneck' cervical collar applied. There was a significant elevation of cerebrospinal fluid pressure in seven of the patients studied when the cervical collar was applied (p < 0.01). This preliminary study raises the possibility that immobilisation of the cervical spine with the 'Stifneck' cervical collar may, by raising the intracranial pressure, contribute to secondary neurological injury in head-injured patients in whom intracranial compliance is already reduced. PMID- 8209991 TI - Spinal anaesthesia for patients with previous lower limb amputations. AB - Phantom limb pain has been reported as a transient phenomenon in patients with lower limb amputations during subsequent spinal anaesthesia. In order to determine its incidence and to define any predisposing factors we prospectively studied 23 spinal anaesthetics in 17 patients with previous lower limb amputation. Only one patient developed clinically significant phantom limb pain and we were unable to define any predisposing factors. Given the low incidence of recurrent phantom limb with spinal anaesthesia, its transient nature, and the fact that it can be treated if it occurs, we conclude that spinal anaesthesia is not contraindicated in patients with previous lower limb amputation. PMID- 8209992 TI - Infra-orbital nerve block for relief of postoperative pain following cleft lip surgery in infants. AB - The study was conducted on 20 infants scheduled for cleft lip repair surgery. Ten were randomly allocated to receive bilateral infra-orbital local anaesthetic nerve blocks at the conclusion of surgery with the other 10 receiving bilateral 'sham' blocks as controls. Postoperative pain relief was assessed using a pain assessment scoring system and by monitoring arterial blood pressure, heart rate and respiratory rate. The mean pain assessment score was significantly higher (i.e. better) (p < 0.05) in the infants receiving the local anaesthetic block. There were no significant statistical or clinical differences in the physiological measurements between the two groups. The infants receiving the block required less analgesia in the postoperative period. The results suggest that infra-orbital nerve block is a simple and effective means of achieving postoperative analgesia after cleft lip repair surgery in infants. PMID- 8209993 TI - Propofol-fentanyl anaesthesia for cardiac surgery. PMID- 8209995 TI - Laryngeal mask cuff pressures. PMID- 8209994 TI - Respiratory arrest following extradural sufentanil. PMID- 8209996 TI - Lasers and the laryngeal mask airway. PMID- 8209997 TI - Laryngeal mask in the prone position. PMID- 8209998 TI - Laryngeal mask airway and late postoperative stridor. PMID- 8210000 TI - Pilot tube of the laryngeal mask airway. PMID- 8209999 TI - Bronchial lavage with a fibreoptic bronchoscope via a laryngeal mask airway in an infant. PMID- 8210001 TI - Confirmation of feeding tube position; how about capnography? PMID- 8210002 TI - Experiences with desflurane. PMID- 8210003 TI - A complication of percutaneous tracheostomy. PMID- 8210004 TI - Silent, unstable, cervical spine injury in multiple neurofibromatosis. PMID- 8210005 TI - Anaphylaxis in pregnancy--the right treatment? PMID- 8210006 TI - Faulty central venous catheter. PMID- 8210007 TI - Another cause of failure of patient-controlled analgesia. PMID- 8210008 TI - A rebreathing non-rebreathing valve. PMID- 8210009 TI - Monitoring line failure. PMID- 8210010 TI - Postintubation uvular necrosis. PMID- 8210011 TI - Preventing postspinal headache: a new technique. PMID- 8210012 TI - Unexpected loss of resistance. PMID- 8210013 TI - Kelene (ethyl chloride) inhaler. PMID- 8210014 TI - Informed consent--recall of risk information following epidural analgesia in labour. AB - Recall of information pertaining to informed consent for epidural insertion in 40 primiparous labouring women was assessed. The recall of informed consent was compared between those patients who had attended antenatal epidural education classes, and those who had not. Overall recall of information was poor. Recall of information was significantly better in patients who had attended antenatal epidural education classes. We recommend that informed consent for epidural analgesia in labour be obtained antenatally whenever possible, and that details of the consent be recorded in the patient's notes. PMID- 8210015 TI - Ondansetron 4 mg for the prevention of nausea and vomiting after minor laparoscopic gynaecological surgery. AB - We studied the efficacy and safety of intravenous ondansetron 4 mg for the prevention of postoperative nausea and vomiting after minor gynaecological laparoscopic surgery in Oriental women. This double-blind randomised study compared ondansetron with placebo, given before the induction of anaesthesia. The anaesthetic technique used thiopentone, fentanyl, atracurium, nitrous oxide and isoflurane. Patients were studied for 24 h with nausea assessed using a verbal numeric scale from 0-10 and emetic episodes recorded as they occurred. Results were available for 102 patients in each group. In the first postoperative hour, fewer patients in the ondansetron Group (12%) had emetic episodes compared with the placebo group (33%, P < 0.01). Nausea score over the first hour (sum of three readings at 0, 30 and 60 min) was lower in the ondansetron group (median 1.6) compared with the placebo group (3.1, P < 0.05). Over the 24 h period, fewer patients in the ondansetron group had emetic episodes (25%) or nausea (43%) compared with patients in the placebo group (56%, P < 0.01) and (58%, P < 0.05) respectively. No adverse events were seen. Ondansetron 4 mg was more effective than placebo in preventing postoperative nausea and vomiting throughout the 24 h after minor laparoscopic surgery. PMID- 8210016 TI - A comparison of the effect of propofol or thiopentone on the incidence and severity of suxamethonium-induced myalgia. AB - We conducted a prospective, randomised single-blind study in 48 adult women undergoing laparoscopic gynaecological surgery to assess the incidence of suxamethonium-induced myalgia. Anaesthesia was induced with either thiopentone or propofol. All other aspects of clinical care were standardised between the groups. The propofol group had a significantly lower incidence of suxamethonium myalgia (19%) compared with the thiopentone group (63%) (P < 0.05). The mechanism of this effect is not understood. PMID- 8210017 TI - Preoperative and postoperative oxygen saturation in the elderly following spinal or general anaesthesia--an audit of current practice. AB - We have compared the incidence of preoperative and postoperative oxygen desaturation in 20 elderly patients undergoing dynamic hip screw insertion for fractured neck of femur, allocated randomly to two groups to receive subarachnoid anaesthesia (SA, n = 10) or a general anaesthetic (GA, n = 10). Oximetry data were recorded during the preoperative night and the first 48 hours after surgery using Satmaster. Data associated with zero amplitude signal were automatically invalidated by the software and decreases in SpO2 which were preceded by contemporaneous changes in signal amplitude which conformed to a previously described template were assumed to be artefactual and were discarded from final data analysis. Data demonstrated a wide interpatient variability. However, those patients who desaturated preoperatively continued to do so in the postoperative period. The differences between the preoperative and postoperative oximetry profiles were examined for each patient and demonstrated a significantly longer time spent with SpO2 < 90% in the GA group compared with the SA group, in all the recorded time periods, except on the day of surgery. The SA group showed an improvement in oxygen saturation postoperatively when compared to the preoperative night, spending less time with an SpO2 < 85%. We conclude that the subarachnoid anaesthetic technique was associated with a lower incidence of postoperative oximetry desaturation when compared with general anaesthetic for these elderly patients undergoing repair of fractured neck of femur. PMID- 8210018 TI - Sodium nitroprusside induced hypotension: haemodynamic response and dose requirements during propofol or halothane anaesthesia. AB - This study was designed to investigate the influence of anaesthesia induced and maintained with propofol on the haemodynamic effects and the dose requirements of SNP during the course of induced hypotension. Twenty-four adult ASA physical status I patients undergoing middle ear surgery were randomly assigned to receive anaesthesia with either morphine, thiopentone, d-tubocurarine, halothane 0.6% end tidal and N2O 70% in oxygen (group I n = 12), or morphine, propofol, d tubocurarine, propofol infusion 108 micrograms.kg-1.min-1 and N2O in oxygen (group 2 n = 12). Mean arterial blood pressure (MAP) was reduced to 60-65 mmHg in all patients using a continuous infusion of sodium nitroprusside (SNP) 0.01%. Propofol produced a significant (17%) reduction in the MAP before institution of SNP infusion. This was related to a 24% reduction in the systemic vascular resistance index (SVRI). In the halothane group SVRI was significantly reduced during SNP infusion. Halothane anaesthesia was associated with significant reflex tachycardia in response to SNP induced hypotension. Eight patients in the halothane group (66%) required propranolol 0.5-3 mg to control tachycardia. Propofol anaesthesia attenuated significantly the reflex tachycardia in response to SNP induced hypotension. Two patients in the propofol group (16%) required 0.5 mg propranolol to control reflex tachycardia. The mean SNP dose requirements were 7.25 +/- 1.6 and 2.1 +/- 1.4 micrograms. kg-1.min-1 in the halothane and propofol groups, respectively (P < 0.0001). None of the patients in the two groups developed rebound hypertension following SNP withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210019 TI - Efficacy of low-dose epidural anaesthesia in surgery of the anal canal--a randomised controlled trial. AB - The aim of the study was to compare in terms of patient comfort, surgical requirements and anaesthetic safety, the difference between epidural and general anaesthesia in patients undergoing surgery of the anal canal. The study was undertaken on 50 adult patients undergoing anal surgery. By random allocation 25 were given a general anaesthetic while 25 were given a low-dose epidural using 0.375% bupivacaine. Advantages and disadvantages of both methods were noted in the study. It was concluded that low-dose epidural is a more effective means of providing analgesia, while maintaining adequate sphincter tone for surgery on the anal canal, than general anaesthesia. PMID- 8210020 TI - Intensive care costing methodology: cost benefit analysis of mask continuous positive airway pressure for severe cardiogenic pulmonary oedema. AB - Costing data for intensive care admissions is important, not only for unit funding, but also for cost outcome analysis of new therapies. This paper presents an intensive care episode costing methodology using the example of a cost-benefit analysis of mask CPAP for severe cardiogenic pulmonary oedema (CPO). This analysis examines the intervention of admitting all patients with severe CPO to the intensive care unit for mask CPAP, compared with the previous practice of admitting only patients failing conventional non-CPAP treatment and requiring mechanical ventilation. The episode costs were determined from a prospective study which showed mask CPAP reduced the need for mechanical ventilation from 35% to 0%. The mean cost of a mask CPAP episode was $1,156, with a mean stay of 1.2 days, compared with ventilated patients, $5,055 and 4.2 days. The major contributors to cost in both groups were nursing and medical salaries, and hospital overheads. The cost of previous estimated yearly caseload of 35 ventilated patients ($176,925) was greater than the cost associated with an increased caseload of 100 mask CPAP patients ($115,600). We conclude that, despite an increase in admissions, mask CPAP for severe CPO is cost-effective. PMID- 8210022 TI - Robertshaw double lumen tubes: a reappraisal thirty years on. AB - A prospective analysis of 100 successive intubations with Robertshaw tubes in patients submitted for routine thoracic surgery is presented. Clinical guidelines for intubation were used as the protocol. Tube position was judged on clinical assessment only and not confirmed with fibreoptic bronchoscopy. In approximately 60% of cases the tubes were judged to be correctly placed on initial introduction. In 20-30% of cases, minor and simple adjustments were required to achieve suitable conditions for one lung anaesthesia. In no case did it prove impossible to achieve conditions adequate for surgery. Common problems related to the endobronchial portion of tubes entering the wrong bronchus, being inserted too far, or not far enough. Two of six episodes of hypoxaemia related to minor problems with tubes and were easily corrected. The experience is compared with that of other workers. The pertinence and implications of the experience and the data to the training of personnel in the techniques of one-lung ventilation and the future of Robertshaw tubes are discussed. It is concluded that the good practical results achieved are specifically related to the Robertshaw design and the material of manufacture. PMID- 8210021 TI - The use of steroids and nebulised adrenaline in the treatment of viral croup over a seven year period at a district hospital. AB - The medical records of 787 patients admitted with a diagnosis of viral croup between January 1986 and December 1992 were examined. The study was prompted by an observed change in the pattern of admissions to the intensive care unit at a large district hospital during the late 1980s. Changes in the pattern of use of adrenaline and steroids were noted. An increase in the dose and frequency of administration of steroids and nebulised adrenaline occurred during the years of the study. In 1992 one-third of patients were given nebulised adrenaline on admission. In the same year 87% of patients were given a dose of steroid. Despite an increase in the number of patients admitted with viral croup, there was a marked reduction in the number of patients requiring admission to intensive care or intubation during the years of the study. This information supports the early aggressive use of steroids and nebulised adrenaline in the management of moderate to severe viral croup. PMID- 8210023 TI - In vitro buffering capacities of proprietary non-particulate antacids available in New Zealand. AB - Four commercially available non-particulate antacid preparations were titrated against 1M hydrochloric acid to assess buffering capacity as compared to 30 ml 0.3M sodium citrate solution. All antacids were used in the manufacturers "unit dose". All antacids tested demonstrated some in vitro buffering capacity, and "Eno" (Reckitt and Colman) had a buffering capacity similar to that of sodium citrate. The retail cost per unit dose was established for each proprietary antacid and for sodium citrate. It was concluded that while proprietary antacids are cheaper per dose than sodium citrate, preparations differ in their acid neutralising capacity. PMID- 8210024 TI - Spinal anaesthesia for caesarean section in the Solomon Islands. AB - Results were kept on 43 spinal anaesthetics performed for caesarean section in the Solomon Islands, a developing tropical country in the Pacific Ocean. A 25 gauge Quincke needle was used and either 2.5 ml of heavy bupivacaine 0.5% or 2.0 2.5 ml of plain bupivacaine 0.5% were injected. Hypotension down to 85 mmHg occurred in four patients and there were no spinal headaches. Five patients had to be given a general anaesthetic. We recommend this technique to other doctors working in the Pacific Islands. PMID- 8210025 TI - Suxamethonium-induced prolonged apnoea in a premature neonate. PMID- 8210026 TI - Awake fibreoptic intubation via a laryngeal mask in an infant with Goldenhar's syndrome. PMID- 8210027 TI - Brachiocephalic vein obstruction: anti-cardiolipin antibody syndrome as a cause of failure of central venous cannulation. PMID- 8210028 TI - Anaesthetic management of a patient with severe bullous lung disease complicated by air leak. PMID- 8210029 TI - Intermittent airway obstruction during anaesthesia in a patient with an undiagnosed anterior mediastinal mass. PMID- 8210030 TI - Inhalation of nitric oxide provides selective pulmonary vasodilatation, aiding mechanical cardiac assist with Thoratec left ventricular assist device. PMID- 8210031 TI - 18th Scientific meeting of the Australian and New Zealand Intensive Care Society. Perth, Western Australia, October 1993. Abstracts. PMID- 8210032 TI - An unusual result of using a laryngeal mask airway. PMID- 8210033 TI - Electronic mail (email) for anaesthesia departments. PMID- 8210034 TI - An unexpected complication of heated hose humidification. PMID- 8210035 TI - Midazolam-opioid combination and postoperative upper airway obstruction in children. PMID- 8210036 TI - Exhale spill valve failure. PMID- 8210037 TI - AIMS and difficult intubation. PMID- 8210039 TI - Positioning of the endotracheal tube. PMID- 8210038 TI - An extreme case of resistance to anaesthetic agents. PMID- 8210040 TI - Amperometric glucose sensors based on immobilized glucose oxidase-polyquinone system. AB - Non-cross-linked and also cross-linked poly(ether amine quinone)s were prepared and tested for their efficiency as electron-transfer relay systems in amperometric glucose biosensors. Cyclic voltammetry and constant applied potential measurements showed that poly(ether amine quinone) relay systems efficiently mediated electron transfer from reduced glucose oxidase to a conventional carbon paste electrode. Sensors containing these relay systems respond rapidly to low (< 0.1 mM) glucose concentrations and reach steady-state current responses in less than 1 min. Electrodes constructed with cross-linked polymer and glucose oxidase were stable, indicating that the glucose oxidase was trapped in the polymer matrix and did not freely diffuse away from the electrode surface into aqueous solutions. The cross-linked polymer is a large molecular system which facilitates a flow of electrons from enzyme to the electrode, acting as an electron-transfer relay system and not as a diffusional mediator. PMID- 8210041 TI - Application of photochemical reaction in electrochemical detection of DNA intercalation. AB - A flow injection analysis (FIA) system for the detection of the compounds that intercalate within DNA is reported. A derivative of 9,10-anthraquinone has been used as the reference compound for photoelectrochemical detection. The sodium salts of 9,10-anthraquinone-2,6-disulfonic acid and 9,10-anthraquinone-2-sulfonic acid are photochemically activated and then reduced in the presence of an electron donor (glucose). The electrochemical signal is based on the measurement of the anodic current resulting from the oxidation of the reduced form of 9,10 anthraquinone. The reduced form of the 9,10-anthraquinone is oxidized through a mediated mechanism at the surface of a tetracyanoquinodimethane-(TCNQ)-modified graphite paste electrode covered by a Nucleopore membrane. TCNQ acts as an efficient mediator for the oxidation of reduced 9,10-anthraquinone. Cyclic voltammetry, photocyclic voltammetry, and the photoelectrochemical FIA response of 9,10-anthraquinone are reported. Experimental results show that these anthraquinones can be intercalated within the helix of double-stranded calf thymus DNA. The anthraquinone molecules that are intercalated within DNA cannot be oxidized due to their limited transport to the modified electrode surface. This results in a decrease in the anodic current at a constant concentration of anthraquinone after intercalation. There is a linear relation between the decrease in electrochemical response and the DNA concentration at a constant concentration of anthraquinone. The intercalated anthraquinone molecules can be completely replaced by another intercalating agent (i.e., ethidium bromide) that is more strongly intercalated within DNA, thereby regenerating the electrochemical response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210042 TI - Fabrication and characterization of low-loss, sol-gel planar waveguides. AB - Applications of planar integrated optical waveguide (IOW) technology to problems in surface spectroscopy and optical chemical sensing have been partly limited by the difficulty of producing high-quality glass IOWs. The fabrication of IOWs by the sol-gel method from methyltriethoxysilane and titanium tetrabutoxide precursors is described here. The physical, chemical, and optical properties of the films during and after high-temperature annealing were studied using a variety of analytical techniques. The results show that the catalyst used to accelerate the sol-gel reaction strongly influenced the optical quality of the IOW. HCl catalysis produced waveguides with propagation losses of approximately 1 dB/cm, whereas in the case of SiCl4 catalysis, propagation losses were < 0.2 dB/cm, a value significantly less than any previously reported for sol-gel derived IOWs. An examination of film surface structure and morphology by scanning electron microscopy and atomic force microscopy showed that the SiCl4-catalyzed IOWs were significantly smoother and more homogeneous on a submicrometer scale than the HCl-catalyzed IOWs. The use of SiCl4 is thought to retard formation of a microheterogeneous network containing Si-rich and Ti-rich domains, which is favored with HCl catalysis and contributes to the higher observed losses. PMID- 8210043 TI - Analytical determination of enantiomeric purity using Raman optical activity. AB - Increased restrictions on the enantiomeric purity of pharmaceuticals underscore the need for improved analytical techniques to quantitate chiral purity. The method of scattered circularly polarized Raman optical activity (SCP ROA) is examined as a potentially useful analytical technique. Preliminary studies revealed SCP ROA measurements were reproducible to within current experimental noise limits and displayed the expected linear decrease in SCP ROA with increasing racemization of the enantiomeric mixtures. Minimal interference in SCP ROA signal was observed when either an achiral or another chiral entity was present in a mixture. The advantages of spectral subtraction techniques were demonstrated for separation of SCP ROA signals when multiple chiral entities are present. SCP ROA has been shown to be capable of quantitative analysis and is capable of simultaneous identification of multiple enantiomeric species. This is significant since traditional optical activity measurements, such as polarimetry and circular dichroism, are of limited value on mixtures where the impurities are not quantitatively defined. PMID- 8210044 TI - Structural characterization of polycyclic aromatic hydrocarbon dihydrodiol epoxide DNA adducts using matrix-assisted laser desorption/ionization Fourier transform mass spectrometry. AB - Matrix-assisted laser desorption/ionization (MALDI) Fourier transform ion cyclotron resonance mass spectrometry (FTMS) has been applied for the structural characterization of four polycyclic aromatic hydrocarbon dihydrodiol epoxide (PAHDE) adducts, including the 5,6-dimethylchrysene DE adduct of 2' deoxyadenosine, the 5-methyl- and 5,6-dimethylchrysene DE adducts of 2' deoxyguanosine, and the benzo[a]pyrene-DE adduct of 2'-deoxyguanosyl 3' phosphate. Measurement of positive and negative ion mass spectra, accurate mass determinations, and CID experiments were carried out using 10-40 ng (20-70 pmol) of sample. An evaluation of five MALDI matrices showed that matrix selection can be used to control the degree of analyte fragmentation. Three MALDI matrices commonly used for the analysis of proteins (sinapinic acid, ferulic acid, 2,5 dihydroxybenzoic acid) gave positive ion adduct mass spectra showing protonated or sodiated molecular ions accompanied by abundant, structurally informative fragment ions. Fragmentation was significantly reduced when working with two matrices used for oligonucleotide analysis (an anthranilic-nicotinic acid mixture and 3-hydroxypicolinic acid). Using the CID capabilities of FTMS, isolation and activation of the MALDI-produced ions was used to provide additional structural information. While characteristic negative ions were not detected for the adenosyladduct, the guanosyl and guanosyl 3'-phosphate adducts gave [M-H]- ions when the anthranilic-nicotinic acid matrix mixture was used. The guanosyl adducts also showed [M-H-2H2O]- fragments. Compared with FAB or FAB-MS/MS for the analysis of underivatized PAH-DE adducts, MALDI-FTMS signals are long-lived, the direct MALDI-FT mass spectra show more structurally informative fragments, and accurate mass and CID experiments require lower sample quantities. PMID- 8210045 TI - Curve fitting for restoration of accuracy for overlapping peaks in gas chromatography/combustion isotope ratio mass spectrometry. AB - The effect of graded degrees of overlap on high-precision and -accuracy carbon isotope ratios determined by gas chromatography/combustion isotope ratio mass spectrometry (GCC/IRMS) is reported. Overlapping peaks of closely matched isotope ratio (difference delta 13CPDB < 1%) were analyzed by the conventional vertical drop summation algorithm and by curve fitting using the Levenberg-Marquardt algorithm. The conventional algorithm resulted in systematic bias related to degree of overlap even though precision was not noticeably affected. The exponentially modified Gaussian (EMG) and HaarhoffVanderLinde (HVL) functions were found to model GCC/IRMS peaks satisfactorily. Useful models over a wide range of overlap were obtained by applying consecutive HVL/HVL or HVL/EMG functions to overlapping peaks. Accuracy was improved in most cases and was never degraded. This study demonstrates the presence of subtle bias in isotope ratio determinations of overlapping peaks and the ability of automated curve fitting to compensate for these biases. PMID- 8210046 TI - Determination of tellurium in urine by isotope dilution gas chromatography/mass spectrometry using (4-fluorophenyl)magnesium bromide as a derivatizing agent and a comparison with electrothermal atomic absorption spectrometry. AB - The antitumor drug AS-101 [ammoniumtrichloro (dioxoethylene-O,O')tellurate(IV)] is the first tellurium-containing compound that has been identified as possessing immunomodulating properties and minimal toxicity. We have developed a stable isotope dilution gas chromatography/mass spectrometry method using 120Te as an internal standard and (4-fluorophenyl)magnesium bromide as a derivatizing agent for Te determination in urine. The urine samples were digested using HNO3 + H2O2 prior to derivatization with lithium bis(trifluoroethyl)dithiocarbamate at a pH of 3. The trifluorodiethyldithiocarbamate of tellurium was reacted with the Grignard reagent in anhydrous diethyl ether to obtain Te-(FC6H4)2 for GC/MS analysis. All isotope ratio measurements were made by selected ion monitoring with a Finnigan MAT 8230 organic mass spectrometer using a 10-m fused silica capillary column. Overall percision values for the five major Te isotopes relative to 130Te were 0.6-3.1% when 10-ng samples of chelated Te were analyzed. No appreciable memory or carry-over effect was observed when two synthetic mixtures differing in 120Te:130Te ratios by a factor of 50 were sequentially analyzed. The isotope dilution GC/MS method was validated by determining Te in urine samples and comparing the values with electrothermal atomic absorption spectrometry. Te concentrations were determined in the 100-500 micrograms/L range with CVs of 1-4%. PMID- 8210047 TI - Principles of ontogenesis of leg and foot in man. AB - Human leg and foot anlagen of different developmental stages were studied by means of light and scanning electron microscopy. The findings were compared with principles of human arm and hand development and results obtained experimentally from chicken limbs. The limbs studied have in common the shaping, cell differentiation, and spatial arrangement of different cells as basic processes of development. On the other hand, upper and lower limbs are very different in human and avian embryos with regard to their position, form, and function. We found that the different positions in relation to the dorsal and ventral surfaces and maintenance of the apical ectodermal ridge (AER) are important factors leading to the different orientations and forms of limbs. The unequal length of the fingers and toes might also be explained in this way. Differences in the position of the most distal muscles in the hand and foot could be a consequence of the cranio caudal sequence of development. The factors controlling the developmental differences between arm and leg are discussed. PMID- 8210048 TI - Distribution of NADPH-diaphorase-positive neurons in the enteric nervous system of the human colon. AB - Recent investigations have demonstrated the colonization of NOS-immunoreactivity and NADPH-diaphorase staining in central and peripheral neurons. The current study investigates the presence and distribution of NADPH-diaphorase-stained nerve cells and fibres in whole-mount preparations of the enteric nervous system of the human colon. Numerous NADPH-diaphorase-stained nerve cell bodies were found in the plexus myentericus and in the plexus submucosus externus. In contrast, we found but very few NADPH-diaphorase-stained nerve cells in the plexus submucosus internus. The majority of the NADPH-diaphorase-stained nerve cells had morphological characteristics similar to those of the Dogiel type I neuron, i.e. possessing broad flat dendrites and one major axonal projection. NADPH-diaphorase-stained nerve fibres can be observed in all three ganglionic networks and in the aganglionic plexus of the circular muscle layer. PMID- 8210049 TI - Ultrastructure and regression of the tunica vasculosa lentis in newborn Wistar rats. AB - In this study, regression of the hyaloid vessels has been followed in the tunica vasculosa lentis (TVL) of the Wistar rat using light, transmission and scanning electron microscopy. The investigation extended from the 1st to the 32nd postnatal day. On day one, the posterior tunica vasculosa lentis is made up of radiating capillaries connected by side-arm branches, the vascular walls of which possess a continuous endothelium, a basement membrane and an incomplete pericyte covering. Endothelial cell specialization is apparent in the form of extreme thinning and fenestration in capillary regions lying opposite the lenticular capsule. The earliest detectable regressive changes become apparent on approximately day 3 and initially involve the short connecting capillaries surrounding the posterior pole of the lens and proceed from there. Regression takes place in the presence of rarefaction of vessel wall cells and the accumulation of endothelial cells in the adjacent capillaries. This leads to the formation of acellular channels which are made up of only basement membrane tubes. After the complete disappearance of these transitional acellular channels, the capillary meshwork coarsens. Remnants of these capillaries are detectable until the 30th postnatal day. PMID- 8210050 TI - A quantitative study on the retial arteries in the bovine fetus. AB - The rostral epidural rete mirabile was injected with latex and the retial arteries were studied quantitatively in three groups of bovine fetuses. It was seen that the differences between the diameters of the right and left retial arteries were not significant. An interesting observation was that the diameter of the internal carotid artery decreased gradually with an increase in the gestational age, but this reduction was made up for the maxillary artery via the rostral rete branches. The proportion of the blood supply to the rete was also determined in three groups of fetuses. PMID- 8210051 TI - Microfibrils: neglected components of pressure-bearing tendons. AB - Some tendons wrap around joints and receive compressive forces besides transferring the tension forces from muscle to bone. These tendons develop a fibrocartilaginous structure which enables them to withstand pressure. This article describes the existence and distribution of microfibrils (or preelastic fibers) in the pressure-bearing tendons of rabbits and dogs by the application of histochemical assays and transmission electron microscopy. Rabbit and dog tendons possess no mature elastic fibers. The rabbit tendon exhibits some response to Weigert's method prior to oxidation which indicates the existence of the so called elaunin fibers, especially in the pressure zone. Oxidation with peracetic acid or oxone discloses intricate aspects of the oxytalan fiber distribution in both tension and pressure zones of the dog and rabbit tendons. Bundles of 12 nm microfibrils were demonstrated in the rabbit tendon by electron microscopy after fixation in the presence of tannic acid. The existence of preelastic fibers in the pressure-bearing tendons has been neglected and they are assumed to have importance in the microarchitecture of the tissue and in the ability of the tendon to support tension and compression forces. PMID- 8210052 TI - Structure and histochemistry of a pressure-bearing tendon of the frog. AB - The plantaris longus tendon of the bullfrog Rana catesbeiana has been structurally and histochemically characterized. The tendon has been shown to wrap around the distal tibio-fibular joint, extending into an aponeurosis. The region under the joint exhibits a large cartilaginous pad. In contrast to the mammalian flexor digitorum profundus tendons, the compression region of the frog tendon is not typically fibrocartilaginous but presents a unique arrangement of convoluted collagen bundles and fibers associated with a large amount of glycosaminoglycans. The sulfated nature of the glycosaminoglycans in the compressed region was determined through enzyme susceptibility as well as through CEC procedures. Cells of the modified zone exhibited morphological variation, from fibroblastic to condrocyte-like. Polarized light analysis revealed an intricate array of collagen bundles which crossed the tendon in different directions and connected the tension and compression regions. The ability of the tendon to resist compressive forces is assumed to be due to the large amount of glycosaminoglycans in the modified region as well as to the complex arrangement of collagen bundles in the tendon as a whole. PMID- 8210053 TI - Immunohistochemical detection of S-100 protein in human deciduous dental pulp. AB - S-100 protein was investigated in the temporary dental pulp by the immunoperoxidase technique, using the avidin-biotin complex method. The results showed that there was a strong positive reaction in the Schwann cells ensheathing axons and nerve fibers. The other cells within the pulp were immuno-negative. S 100 protein and the results of the present study are discussed. PMID- 8210054 TI - Anatomical and histological re-examination of Appendices colli in the goat. AB - Appendices colli (App. colli) were investigated by anatomical and histological methods in the goat. App. colli were composed of elastic cartilage located at central and the skin covering the cartilage, which included arterioles along the cartilage and nerve bundles. Three types of muscles connected to App. colli; superficial muscle bundles, a branch of the omohyoideus muscle, and a muscle arising from the pharyngeal raphe (appendico-pharyngeal muscle). The latter two muscles were connected to the root of the App. colli where the muscle fibers transformed into the perichondrium of the elastic cartilage. The appendico pharyngeal muscle was innervated by branches from the glossopharyngeal nerve which were composed of myelinated nerve fibers. The subcutaneous area of the App. colli was supplied by cutaneous rami of the vagus and the second cervical nerves. The innervation and the musculature confirmed that the cartilage of the App. colli were derived from third and fourth branchial arches. PMID- 8210055 TI - A case in which a branch from the superior gluteal nerve innervated the rectus femoris and the vastus lateralis. AB - During dissection of the gluteal region, a branch from the most cranial root of the superior gluteal nerve was found to innervate the rectus femoris and the vastus lateralis on the right side of a 41-year-old Japanese male cadaver. This case is an example of Eisler's so-called "competition for innervation areas" (Eisler 1895). PMID- 8210056 TI - [Modern image analysis processes as support for spatial reconstruction of histological structures]. AB - Spatial reconstruction of anatomic and histologic structures is of increasing importance in biological and medical research. A special kind of disease- hereditary opalescent dentine (HOD)--offered a good chance for the use of a comfortable image-analysis system (IBAS, Kontron) in combination with a special software for three-dimensional reconstruction. New aspects of the morphologic organisation of a key structure of HOD--the giant dentinal canals--could be shown, thus supporting the hypothesis of a vasal origin. PMID- 8210057 TI - Muscular composition of the gastric groove in the golden hamster. AB - The golden hamster possesses a forestomach and a glandular stomach. The gastric groove connects the cardia to the glandular stomach and is situated on the lesser curvature of the stomach. The constitution of the muscle fibers in the gastric groove was investigated. The gastric groove consisted of two lips and a groove floor. The muscle coat of the lips was composed of a mixture of smooth and striated muscle fibers. The smooth muscle fibers were components of the cardiac muscle loop. The striated muscle fibers were extensions from the esophageal inner circular muscle layer, and invaded about half the length of the lips. The muscle coat of the groove floor consisted of an inner circular muscle layer made up of smooth muscle fibers, and the outer longitudinal muscle layer of the striated muscle fibers extended from the esophageal outer longitudinal muscle layer. The present study revealed that the muscle coat of the gastric groove in the golden hamster was composed of smooth and striated muscle fibers, and that these striated muscle fibers were extensions of the esophageal muscle coat. PMID- 8210058 TI - Morphometric evaluation of paranasal sinuses for endoscopic sinus surgery. AB - Endoscopic surgical treatment of paranasal sinus infections is currently being applied in many Otorhinolaryngology Clinics. Although high rates of success are reported with this treatment method, life threatening complications sometimes do occur due to disorientation, especially when angled telescopes are used. In order to avoid such complications, we evaluated the distances from the anterior nasal spine to various important anatomic structures encountered during endoscopic surgery. The measurements obtained by a morphometric anatomic study of cadavers are presented in this study. We believe that if surgery is carried beyond the measured distances, serious complications may ensue during endoscopic surgery. PMID- 8210059 TI - [Scientists in German anatomical institutes--number, service positions, qualifications and gender]. PMID- 8210060 TI - [Biological diagnosis of pheochromocytoma: impact of technological improvement]. AB - Laboratory diagnosis of pheochromocytoma must give evidence of increased catecholamine production. This requires measurement of catecholamines and their metabolites (normetanephrine NMN, metanephrine MN and/or VMA) in urine or in plasma. The various assays can be also performed during dynamic test that stimulate or inhibit catecholamine release. The recent introduction in biochemistry of high performance liquid chromatography coupled to electrochemical detection (HPLC-ED) has greatly reduced drug-induced interference and has therefore narrowed the reference value range. The two groups of compounds that have most benefited from such analytical improvements are urinary metanephrines and VMA. The technical progress has greatly simplified the laboratory diagnosis of pheochromocytoma both by improving the reliability of already available compounds and by favouring the development of news markers. However, the diagnostic sensitivity of the various urinary and plasmatic markers remains very unequal and the diagnosis of pheochromocytoma requires a carefully planned sequence of studies including appropriate biochemical tests able to affirm or to exclude the diagnosis with a high degree of security while reducing the duration and cost of the investigation. Among urinary markers, metanephrines remain the most direct indices of catecholamine hypersecretion and provide the most reliable biochemical indicators of the existence of pheochromocytoma. The diagnostic sensitivity of urinary metanephrines (about 98%) greatly exceeds that of catecholamines and VMA (60-70%). These differences are related to the diversity and specificity of physiological mechanisms involved in the synthesis, the release and inactivation of markers (catecholamines, metanephrines, VMA) and to the variety of clinical presentations and secretory patterns of pheochromocytomas. Considering the practical necessity of simplifying the collection of laboratory samples, use of plasma assays for the diagnosis of pheochromocytoma has become increasingly routine. However, plasma catecholamines- even when assayed during the clonidine suppression test--have not fully lived up to expectations. The diagnostic sensitivity is far better (about 98%) with the recently developed assays of plasma methoxyamines which, owing to their long half life, provide long-lasting indicators of the catecholamine discharge and are elevated even in tumors without clinical expression. Laboratory diagnosis is relatively easy when the patient bears a large tumor releasing considerable amounts of catecholamines and metabolites; it becomes more challenging in the case of small tumors or of pretumoral hyperplasia in which only the most reliable biochemical markers are able to confirm the diagnosis of pheochromocytoma. PMID- 8210061 TI - Structural characterization of abnormal hemoglobins from dried blood specimens in a neonatal screening program. AB - Blood specimens dried on filter paper are now widely used for neonatal screening of hemoglobinopathies. These samples are perfectly suited for electrophoresis studies and HPLC analysis. They may also be used for DNA analysis. The structural characterization of a hemoglobin variant is also possible using protein chemistry methods. After elution of the hemoglobin from the paper, the different components are fractionated by a microscale preparative isoelectric focusing. The structural modification of the abnormal hemoglobin is then determined through a series of techniques including chain separation, aminoethylation, trypsin digestion, analysis of the peptides and determination of their aminoacid composition. The efficiency of this strategy is demonstrated by the study of an alpha-chain variant (Hb Hasharon) and three beta-chain variants (Hb S, Hb D Punjab, Hb E). Unambiguous identification of the structural abnormality was obtained with samples stored for up to 18 months and with abnormal fractions amounting to only approximately 10% of the total lysate. PMID- 8210062 TI - Free triiodothyronine (FT3) EIA-BioMerieux. Analytical and clinical evaluation. AB - We tested a new immuno-enzymatic kit: FT3-EIA BioMerieux, for direct measurement of FT3. Precision is good, with coefficients of variation below 10%. Detection limit is 0.4 pmol/l. We tested some anticoagulants and the specificity of the antibody. Results appear to be independent of plasmatic concentration of albumin and TBG. Reference range was determined to be 3.7 to 8.7 pmol/l. A clinical study, in comparison with isotopic method FT3-Coat-RIA BioMerieux shows that this non-isotopic kit is available, even for low concentrations. PMID- 8210063 TI - [Evaluation of the Vidas system for the serological diagnosis of toxoplasmosis]. AB - The recent immuno-analysis system Vidas (bioMerieux) for the serological diagnosis of toxoplasmosis was compared to the Abbott Toxo EIA system, taking the indirect immunofluorescence assay (IFA) as reference for immunoglobulin G and the immunosorbent agglutination assay (ISAGA) for immunoglobulin M. Five hundred and ninety-four individual sera and 15 seroconversions or recent infections (39 sera) were studied. Sensitivity and specificity of the Vidas system were respectively 99.7% and 99.4% for IgG, and 100% and 97% for IgM. During primary toxoplasmia infection, the Vidas system allows very early detection of the appearance of IgM and IgG. The Vidas Toxo IgG is more sensitive than the Abbott G EIA. For IgM, the Vidas Toxo M is less specific but much more sensitive than the Abbott M EIA. PMID- 8210064 TI - [Profile of hepatic and muscular acylcarnitines in chronically hyperammonemic mice after an acute treatment with sodium benzoate: dose-response study]. AB - Sodium benzoate is conjugated with glycine in the liver and the kidney, which may cause the elimination of one mole of alpha-amino N for each mole of benzoate administered. However, muscle does not possess the enzyme activity to form benzoylglycine. The object of this study was to identify the secondary effects of acute sodium benzoate treatment on the concentrations of carnitine in liver and muscle when the glycine availability in these tissues is still assured. Our studies are based on chronically hyperammonemic spf/Y mice with a deficiency of ornithine transcarbamylase. The animals were given 2.5, 5.0 and 10.0 mmol/kg sodium benzoate intraperitoneally. Control groups of normal mice received identical treatments. Our results demonstrate that sodium benzoate influences the homeostasis of liver and muscle carnitine after only 15 minutes of treatment. We observed a reduction of short- and medium-chain acylcarnitines in the liver of normal mice, and an increase of free carnitine and long-chain acylcarnitines in the spf mice. In muscle, we found a reduction of free carnitine and short- and medium-chain acylcarnitines at doses of 5.0-10.0 mmol benzoate/kg in the normal mice. However, we observed a significant reduction of long-chain acylcarnitines in muscle tissue from spf mice. The carnitine concentrations in each tissue differ depending on the dose of sodium benzoate administered, which may suggest a biphasic effect. Our results indicate that sodium benzoate has a secondary effect on the liver and muscle concentration of carnitine from the beginning of its intramitochondrial metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210065 TI - Glycated immunoglobulin M in diabetic patients. AB - Measurement of glycation levels on isolated immunoglobulin M (IgM), a short half life protein, could be an index of glycaemic control. We determined glycated IgM levels in a diabetic patients population as compared to control non-diabetic subjects in a cross-sectional and longitudinal study. For that purpose we developed a precipitation method for IgM purification, measured glycation on the purified protein by a nitroblue tetrazolium assay and correlated glycated IgM, glycated haemoglobin (HbA1c) and fructosamine rates. The purification method we developed comprises dextran sulfate-CaCl2, ammonium sulfate and polyethylene glycol precipitations and it allows extraction of IgM free of contaminants as shown by immunoelectrophoresis. Glycated IgM levels were 8.65 +/- 0.15 nmol deoxymorpholinofructose (DOMF) equivalents/mg protein for non-diabetic subjects (n = 30) and 12.08 +/- 0.60 nmol DOMF equivalents/mg protein (n = 67) for diabetic patients. Diabetic patients had then a 40% rise in glycated IgM (p < 0.0005). In a longitudinal study with patients undergoing treatment aimed at improving their metabolic control, glycated IgM levels decreased significantly (p < 0.001) between the day of admission and the fifth day. Average rate of fall was 13% with a range of 3.0 to 22.0% (n = 28). Glycated IgM clearly responds more rapidly than fructosamines which fell by 7.0% and than HbA1c, which showed a rate of fall of 3.9% in the same period. A significant positive correlation was found between these parameters, being stronger between glycated IgM and fructosamines. This method could provide an alternative approach as a short-term marker of glycaemic control for clinical trials. PMID- 8210066 TI - Comparison of three primer sets for the detection of Mycobacterium tuberculosis in clinical samples by polymerase chain reaction. AB - A number of studies have underlined the interest of the polymerase chain reaction (PCR) in the detection of Mycobacterium tuberculosis in clinical samples. Among the different parameters to be carefully studied the choice of target gene and primers is essential. The amplification of nucleotidic sequences localised on three different target genes (groEL, IS6110, Pab) was examined in 196 clinical samples from patients with suspected tuberculosis or receiving antituberculous therapy. The results obtained after hybridization with non-radioactive labelled probes were compared with the culture data. None of the primer sets studied showed a satisfactory sensitivity (79% to 84%) suitable for it to be used alone. The false-negative specimens with the PCR tests usually corresponded to those that contained few mycobacteria. With the methods described in this study, the use of two or three primer sets located on different target genes allowed to improve the positivity rate compared to the culture and sensitivity of the test (90-98%), particularly for paucibacillary samples. On the other hand, the interpretation was easier when concordant results were obtained. PMID- 8210067 TI - Transcutaneous devices for the measurements of pO2 and pCO2. State-of-the-art, especially emphasizing a pCO2 sensor based on a solid-state glass pH sensor. AB - In treating critically ill neonates it is vital to ensure optimal delivery oxygen to the tissue and simultaneously make sure that carbon dioxide is removed from the tissue. The continuous non-invasive transcutaneous measurements of pO2 and pCO2 make it possible to detect sudden changes in pO2 and pCO2 immediately, so prompt corrective action can be implemented to ensure optimal neonatal patient care. A new combined solid state transcutaneous sensor for measurement of pO2 and pCO2 is described in the paper. The pO2 part of the sensor has been redesigned and its performance improved to ensure more reliable pO2 readings during in vivo measurements. The pCO2 part of the sensor has been completely redesigned. The application of a new solid state technology in the production of the pCO2 combined with the use of a new, reinforced, composite pH sensitive glass membrane, has resulted in an extremely robust and reliable pCO2 sensor. PMID- 8210068 TI - The application of saliva, sweat and tear fluid for diagnostic purposes. AB - Despite anatomical and biochemical similarities, salivary, sweat and lacrimal glandulas differ in their physiological functions. Salivary and tear fluid are required for the proper function of the epithelial layer from which they are secreted. The physiological function of sweat is the elimination of excess heat. The products of the three glandulas can be used to measure indicators either of glandula or of non-glandular diseases. In the latter case the indicator must be transported from the particular organ to the glandula where it is then secreted. In sweat, only one example has reached well accepted clinical importance. The measurement of electrolyte concentrations is the classical laboratory test for cystic fibrosis. The use of tears for diagnostic purposes has been proposed for drug monitoring, to verify the dry eye syndrome (Schirmer test), to detect lysosomal storage diseases (eg Morbus Gaucher) and hyperglycemia. The major domains for the application of saliva are hormone analyses (especially of steroids) and drug monitoring. Furthermore, the application of saliva has been proposed for the detection of several other analytes (eg secretory IgA, peptide hormones, HIV antibodies). PMID- 8210069 TI - Diffusion-sink sampling for minimally invasive measurement of tissue available hormones. AB - The interpretation of hormone concentrations measured in blood plasma is made difficult by some features of hormone physiology that are common to many endocrine systems: 1) secretion occurs in episodes; and 2) specific binding proteins profoundly influence the availability of hormone to tissue. Frequently repeated sampling and specific measurement of the freely diffusing hormone concentration are thus desirable. Traditional methods to this end are invasive, laborious, and frequently impractical. Diffusion-sink (DS) devices that are able to continuously sample the freely-diffusing concentration of a hormone in a biological fluid over a period of time have been built; these devices can be used for minimally invasive sampling. For some steroid hormones, DS devices can be worn orally to estimate tissue-available hormone in saliva; direct installation of DS devices in interstitial fluid is also possible. Experience to date in using these devices to measure corticosteroids and progesterone suggests several practical advantages, including: 1) similar time-averaging capability as with invasive area-under-the-curve methods; 2) specificity for the freely-diffusing concentration even in the presence of varying concentrations of protein-bound forms; and 3) ability to sample under conditions where traditional methods are prohibitively invasive, such as normal work and sleep. The diffusion-sink sampling approach can probably be combined with appropriate immunoassay methodologies to yield measurements that are simple and quick enough for routine clinical use. PMID- 8210070 TI - Hybrid Rop-pIII proteins for the display of constrained peptides on filamentous phage capsids. AB - In order to increase the versatility of phage display technology, it is desirable to be able to impose some structural constraints on the peptides that are presented by the phage particles. This is currently not feasible since the conformation of the capsid proteins, used to link the foreign peptide to the phage, are either unknown (pIII) or too simple (pVIII) to permit the engineering of peptide inserts into a constrained context. To reach this scope we have modified the amino-terminus of gene III by appending a well-characterized protein motif, the four-helix bundle of the bacterial protein Rop. Phage particles displaying Rop can be separated from wild-type (wt) particles by affinity purification with an antibody. Rop can be extensively modified by substituting its solvent-exposed residues and/or by inserting peptides either into the carboxy terminal tail or into the bend region that connects the two alpha-helices of the monomer. These results open the possibility to construct peptide libraries where the peptides are constrained either into an omega-loop type conformation or an alpha-helix. Libraries formed by peptides inserted into the carboxy-terminus can also be constructed. Furthermore, the system that we have developed permits to produce large quantities of the elements of the libraries in the cytoplasm or to display them on the capsid of filamentous phages. PMID- 8210071 TI - Detection of the expression of the Epstein-Barr virus latent gene product in Hodgkin's lymph nodes by immunostaining. Comparison between paraffin sections and imprints. AB - The latent membrane protein (LMP) of Epstein-Barr virus can be detected by an immunostaining method in about 50% of Hodgkin's disease lymph node tumour cells on frozen sections. The same method had been successfully employed on paraffin embedded (PE) sections. We used this immunostaining method on imprints (IP) and PE sections of 26 Hodgkin's lymph nodes. Overall, there were 11 LMP-positive cases; immunostaining was stronger in IP than in PE samples; in nine cases both IP and PE samples were LMP-positive; in two, imprints were LMP-positive when PE sections were LMP-negative. PMID- 8210072 TI - [Microsporida microsporidiosis]. AB - Microsporidia were infrequent in man until 1985. A new species, Enterocytozoon bieneusi, responsible for diarrhea, was described in AIDS patients in 1985. Little is known about the parasite; its diagnosis is difficult, and its incidence certainly underestimated. This work summarizes current knowledge on microsporidia (parasitology, clinical features, diagnosis and drug therapy). PMID- 8210073 TI - [Evaluation of the technique of CKMB assay using Ektachem (500 and 700)]. AB - The aim of this study was to compare the dry-chemistry CKMB Ektachem method to a liquid immunoinhibition method (Merck/Cobas Bio) and to the electrophoretic method (Helena France), both on patients (n = 95) and control (4 specimens from different commercial origin) sera. The Ektachem method was found linear in the range tested (7 to 97 U/l). Within run imprecision tested with low, medium and high control sera were satisfying (CV 3-4%) as well as between run imprecision (CV < 10%), for CKMB activities of at least 30 U/l. As compared to the liquid immunoinhibition method (Merck), the results of patient sera were very close but slightly lower (y = 0.97x-1; r = 0.74; y = Ektachem, x = Merck). As compared to the electrophoretic method, the Kodak Ektachem method showed a specificity of 74% and a sensitivity of 85% (n = 95). A close agreement (r = 0.73) between these two methods was obtained for samples with a total CK activity at least 3 times over the upper limit of normal range. We therefore conclude that the Kodak Ektachem CKMB method allows a rapid and easy determination of CKMB activity for samples undergoing total CK activity 3 times over the upper limit of normal range. Like all liquid immunoinhibition methods, the Kodak Ektachem method shows some lack of specificity and does not show a better concordance with the electrophoretic method than does the Merck/Cobas Bio method. PMID- 8210074 TI - Clinical relevance of IgG subclass deficiencies. AB - Patients with primary or secondary IgG subclass deficiencies suffer from infections due to encapsulated microorganisms such as H influenzae and pneumococci. In addition to relapsing infections, some patients with primary subclass deficiencies may have autoimmune disorders. The best characterized defect in IgG2 deficiency, either isolated or combined with IgG4 deficiency. It is frequently associated with IgA deficiency or with ataxia telangiectasia. IgG1 deficiency occurs mostly in combination with disturbances of other immunoglobulin isotypes, and probably represents a form of common variable immune deficiency. Decreased IgG3 levels were reported in association with lung dysfunction and viral diseases. Except in IgG1 deficiency, total IgG serum levels in primary as well as secondary IgG subclass deficiency states may be normal or even increased. It is assumed that IgG subclass deficiencies represent an indicator of more basic immunologic abnormalities. There is evidence that antibody defects correlate better with the clinical symptoms than the total serum IgG subclass concentrations. In patients with severe recurrent infections and IgG subclass deficiency, intravenous immunoglobulin treatment at dosages of 0.3 to 0.4 g/kg body weight every 3-4 weeks is indicated. PMID- 8210075 TI - Serum IgG subclass level determination: methodological difficulties and practical aspects. AB - During the last decade, the availability of monoclonal antibodies against human IgG subclasses led to a marked increase in serum IgG subclass determinations, including in routine laboratories. Although several drawbacks of polyclonal antisera (poor specificity except in certain precipitation assays, inter-batch variability, etc) are avoided by the use of monoclonal antibodies, a number of methodological difficulties and pitfalls still remain, especially for measurement of IgG2 and with commercial kits. Moreover, most of them are hardly practicable, because of arbitrary standardization and absence of appropriate normal reference values. This increase in routine serum IgG subclass level determination led to a considerable widening of patient recruitment and a significant evolution of patterns and frequencies of subclass deficiencies was observed in patients with unexplained infection and no characterized immunodeficiency syndrome, as compared with initial studies performed in specialized clinical immunology departments. IgG3 deficiency is more frequent in mildly than in severely infected patients, and a marked decrease in the incidence of IgG2 deficiency was found in our recent survey. We also present the results of a recent retrospective study on hypogammaglobulinemia. In this condition, IgG subclass imbalances are more frequent than an overall IgG subclass decrease, and IgG2 deficiency appears to be a marker of severity. Other observations are: 1) the high frequency of selective IgG1 deficiency, especially in adults over 40 years; and 2) that of IgG2 deficiency in children of less than 4 years of age. PMID- 8210076 TI - Effector mechanisms activated by human IgG subclass antibodies: clinical and molecular aspects. Review article. AB - Secondary systemic immune responses are predominantly of the IgG class and passive administration of intravenous IgG, from pooled normal serum, is an effective prophylactic and/or therapeutic treatment for patients with defined immunodeficiencies. However, the proportions of each IgG subclass present within a specific antibody response may differ dramatically from that of the total IgG pool. For some antigens the response may be essentially restricted to a single subclass and it may be presumed that the antibody isotype produced has an optimal protective role. The clinical consequences of selective IgG subclass deficiency appears to validate this presumption. In this review we emphasize the differences in effector functions activated by the IgG subclasses and hence the mechanisms responsible for the removal and destruction of antigen/antibody complexes. These studies are relevant to diagnosis and treatment of patients with recurrent infection; the IgG isotype of monoclonal antibodies selected for passive in vivo therapy; the generation of customized antibodies having a pre-determined profile of effector functions and 'immuno-direction' with new vaccines to provoke an antibody response having an isotype profile optimal for the proposed application. PMID- 8210077 TI - The application of molecular biology techniques to the diagnosis of hyperlipidaemia and other risk factors for cardio-vascular disease. PMID- 8210079 TI - The role of the hygienist in biological monitoring. PMID- 8210078 TI - [Updating of relative data on tocopherols in clinical biochemistry]. AB - The working group on lipophilic vitamins of the FSBC has reviewed current knowledge in the field of tocopherols and tried to summarize the most important and recent aspects that may be useful to clinical practitioners. The molecular structure of tocopherols and tocotrienols, their biogenesis, their analysis in foods, their metabolism in humans, their measurement in biological fluids, and the organism's needs and dietary requirements are reviewed. Their main functions as antioxidants and free radical scavengers are described at the molecular, ultra structural, cellular and organ levels. The interest of these vitamins in three pathologies in which oxidative-stress has been implicated (atherosclerosis, cancer, kidney failure) is discussed. PMID- 8210080 TI - Exposure to metallic catalyst dust: manufacturing and handling of catalysts in the chemical industry. AB - The exposure of workers to metallic catalyst dust was assessed in manufacturing and reprocessing industries, and during catalyst handling in the chemical industry. The level of exposure was found to be generally low during the manufacturing and reprocessing activities taking place in permanent installations, and extremely variable during catalyst handling performed by workers of sub-contracting specialized firms. The difficulties in treating the occupational hygiene problems of these workers are pointed out. PMID- 8210081 TI - Detecting plant silica fibres in animal tissue by confocal fluorescence microscopy. AB - Silica fibres from the inflorescence bracts of the grass Phalaris canariensis L. cause dermatitis, and have been implicated in the aetiology of oesophageal cancer in northeastern Iran. Here we describe a method for labelling these fibres so that they can be located in mammalian tissue. Fluorescein was covalently linked to isolated, purified fibres with the silane coupling agent 3-aminopropyl triethoxysilane. The labelled hairs were then rubbed into the backs of mice. These were later killed and their skin fixed, stained and sliced at a thickness of 250 microns. A confocal laser scanning microscope gave brilliant images of the fibres at any depth up to 100 microns or more beneath the surface of the slice. Fibres penetrated deeply into the dermis. Several cubic millimetres of tissue could be surveyed in 1 h. The number of fibres present was approximately 2 mm-3 initially, falling to 0.1 mm-3 after 7 days. PMID- 8210082 TI - Occupational exposure to chromium and nickel in Finland--analysis of registries of hygienic measurements and biological monitoring. AB - Two large data bases, one with the results of analyses on total dust, nickel, total and hexavalent chromium, and the other, with concentrations of chromium and nickel in workers' urine, have been accumulated in the Finnish Institute of Occupational Health. Data were analysed to assess occupational exposure to chromium and nickel during the last decade, using the International Standard Industrial Classifications for grouping industrial activities. Number of analyses was highest in fabricated metal products manufacturing, and welders and sheet metal workers were the largest and most heavily exposed groups. Occupational exposure limits were exceeded in 15.8% of all chromium measurements (500 micrograms m-3 for total chromium and 50 micrograms m-3 for hexavalent chromium). Recommended biological action level (BAL) (1.0 mumol l.-1) was exceeded in 0.8 7.1% of the cases in different years. Altogether, 18.3% (range 7.6-28.3%) of the air nickel measurements were higher than the occupational exposure limit for nickel compounds (100 micrograms m-3), but only 0.2-3.1% of results exceeded the BAL for nickel (1.30 mumol l.-1). PMID- 8210083 TI - Health problems associated with nickel refining and use. AB - After a brief mention of history and world use the authors review the major hazards to health associated with nickel and its compounds. These include pulmonary and sino-nasal cancer from exposure to the dusts involved in certain, now obsolete, processes, dermatitis and nickel carbonyl poisoning. Brief mention is also made of other less well established or hypothetical health risks mentioned in the nickel context including asthma, pulmonary fibrosis and acute poisoning. In conclusion the authors mention some current work being undertaken in the occupational health field and give sources of further information. PMID- 8210084 TI - Influence of an anti-oxidant on the formation of allergenic compounds during auto oxidation of d-limonene. AB - Butylated hydroxytoluene (BHT), a common anti-oxidant, was added to different samples of d-limonene. The decrease in concentration of d-limonene and the formation of oxidation products were compared between the samples and with samples without anti-oxidant using gas chromatography. The aim of the study was to investigate how long d-limonene to which BHT was added could be handled when air-exposed at room temperature, without formation of oxidation products which according to previous studies increase the risk of skin sensitization. In experiments trying to mimic the handling of limonene products at workplaces the addition of BHT prevented auto-oxidation for periods depending on the purity of the products and on the room temperature. Cold and dark storage of d-limonene in closed vessels prevented auto-oxidation for 1 year without addition of anti oxidant. PMID- 8210085 TI - Concentrations of cadmium in air and urine in an alkaline battery works. AB - Concentrations of cadmium in air are available for exposed workers in an alkaline battery factory from 1965, and of cadmium in urine concentrations from rather later. Using simple statistical methods annual data sets have been analysed by department, job or other classification. Summary results of concentrations of cadmium in air from 1965 and in urine from 1970 are examined, and show a steady annual reduction. No attempt is made to relate changes in concentrations to changes in manufacturing practice or control measures, although the effects of one major change are noted. Relations between concentrations of cadmium in air and in urine since 1970 are reported. Those between cadmium in air and recent concentrations of cadmium in blood and of beta 2-microglobulin in urine are commented on. The kinetics of cadmium absorption, partition and excretion are not considered in any depth. PMID- 8210086 TI - Audiometry in industry. AB - Pure tone audiometry is the most common method of screening for hearing loss. The test itself is straightforward and the equipment readily available, so it forms part of the hearing conservation programmes of many industries. Whilst the test itself is straightforward, because of individual variability in response, interpretation of the results may be difficult. There has therefore been considerable debate on the role of audiometry in hearing conservation. The last official publication dealing with audiometry was a Health and Safety Executive discussion document 'Audiometry in Industry' published in 1978: no current recommendations are available. This article is a critical review of the advice given in that document, which aims to clarify the role that audiometry may play in the conservation of hearing. It was concluded that audiometry in the individual may perform poorly in strict cost benefit terms when used serially to detect a deterioration in hearing of an individual, but as the only form of biological monitoring it should be available to all employees who are advised to wear hearing protection at work. A distinction between audiometry in the individual and group audiometry is then made: the analysis of the hearing of a group may be useful in assessing risk to hearing. Graphical methods of analysis are shown, and more formal methods of statistical analysis discussed. PMID- 8210087 TI - Changing horses--a response. PMID- 8210088 TI - [Value of imaging in sphenoid sinus diseases. Role of magnetic resonance]. AB - The authors use case studies to illustrate the respective benefits of CT and MR imaging in the management of sphenoid sinus disease. Because the sphenoid sinus is located deep in the skull base adjacent to vital neurological and vascular structures, surgery involves a certain risk. The improved quality of imaging now available provides essential information on which to base therapeutic options. Since CT and MR findings make it possible to increase the precision of the pretherapeutic evaluation and to determine neurological and vascular involvement, these imaging studies have become an integral part of the successful management of sphenoid sinus disease. PMID- 8210089 TI - [Expression of oncogenes C-myc, C-raf and N-ras in advanced cancers of the upper respiratory and digestive tracts. Correlation with tumor clinical response to chemotherapy]. AB - A correlation between oncogenes expression (N-ras, C-myc, C-raf) and response to neoadjuvant chemotherapy has not been established in carcinology of the head and neck yet. We have studied the expression of these three oncogenes in 24 tumors patients with squamous cell carcinoma previously untreated. Tumors samples were biopsed before initiation of treatment. After extraction of total RNAs, oncogene expression was measured by northern and slot blot analysis using 32P radiolabeled probes. The endoscopic, histological and clinical response was evaluated after chemotherapy (5-FU: 1 g/m2/d, D1 to D5; CDDP: 100 mg/m2 at D1, 3 courses every 3 weeks). There was no significant difference of N-ras expression between responding or resistant tumors to chemotherapy. However, there was a significant difference of C-myc (p < 0.05) and C-raf (p < 0.01) expression between the two patients population: C-raf and C-myc expression were higher in the responding tumors than in the resistant tumors to chemotherapy. In conclusion, C-myc and C raf expression could be a marker for chemosensitivity. PMID- 8210090 TI - [Cell culture in thyroid cancers]. AB - The authors studied the diagnostic interest of cell cultures in thyroid tumors. They cultivated 10 tumours (4 papillary carcinomas, 5 medullary carcinomas and 1 sarcoma-looking tumour). In 7 cases, cultures yielded nothing more than pathologic examination. Nonetheless the study allowed to detect a double secretion (calcitonin and thyroglobulin) in 2 medullary carcinomas which turned out to be mixed proliferations. It also detected a production of thyroglobulin by the sarcoma. They think that cell cultures may have a diagnostic interest besides pathologic examination, allowing precise study of secretory features of the tumors. PMID- 8210091 TI - [Human papillomavirus and nasosinusal inverted papilloma]. AB - Eight inverted papillomas were evaluated for the presence of human papillomavirus (HPV) DNA. The techniques used were Southern Blot Hybridization in five cases and Polymerase Chain Reaction (PCR) in three cases. All eight lesions contained the characteristic features of inverted papillomas. Two lesions showed areas of dysplastic change and one lesion contained koilocytes. In three patients, invasive squamous cell carcinomas were found. The presence of HPV was noted in one of these specimen of inverted papilloma with squamous cell carcinoma. Specific testing for HPV types 6, 11, 16, 18 and 33 on this specimen was negative, thus indicating that the specimen is associated with a different HPV type. The results of this study, with only one case of positive HPV testing, leads us to question the precise role of HPV as an etiological agent in nasal inverted papillomas. The fact that this single positive case did not test positive for the HPV type 16 suggest that this is not the only "high risk" HPV type associated with the progression of inverted papilloma to a carcinoma. PMID- 8210092 TI - [Physiopathological and therapeutic values of experimental model of acute otitis media. Review of the literature]. AB - The animal model of acute otitis media (AOM) has been widely used to study the pathophysiology and treatment of this disease. Different authors have demonstrated a both mechanic and immunologic role of concomitant viral infection in the pathogenesis of AOM. The specific immune response was found mainly local in otitis media due to S. pneumoniae and systemic with H. influenzae. Local and systemic complications are currently precise. This model was proved useful in pre clinical evaluation of antimicrobial agents and development of vaccines. PMID- 8210093 TI - [Malignant external otitis. Apropos of 7 recent cases]. AB - Seven recent malignant external otitis are described. The authors report criteria of both etiology, bacteriologic, radionuclide scanning computed tomography. Now, for the positive diagnosis, the radionuclide scanning is essential. The computed tomographic scan provided the best anatomic imaging of the infection process. The treatment of choice is systemic antibiotic therapy as fluoroquinolones antibiotic. This antibiotic is active against P. Aeruginosa and has an excellent bone penetration. Only one patient died and another suffered from osteomyelitis of the base of the skull. The radionuclide scanning is very important for criteria of healing, particularly about stoppage of systemic antibiotic therapy. PMID- 8210095 TI - [Nasosinusal schwannoma. Apropos of 2 cases. Value of nasal endoscopy for diagnosis and treatment]. AB - Two cases of paranasal schwannomas are reported. These tumors are rare. Its symptomatology is no specific explaining the late diagnosis. The contribution of radiology and endoscopy for this pathology is analysed. Ct scan and MRI state precisely the extension and the relations of the tumor. Endoscopy improves the endonasal exam pre and post operative and may be an option for the surgical treatment of these tumors. In connection with that we present an original approach of the pterygopalatine fossa under endoscopic control via the middle meatus. PMID- 8210094 TI - [Herpes of the larynx. Apropos of 3 cases]. AB - Herpes laryngis is a rare inflammatory disease, caused by herpes simplex (HSV) or herpes zoster virus (HZV). Three cases of acute viral laryngitis are described. The first case of laryngitis is caused by HZV, with involvement of VII., VIII., IX. and X. cranial nerves. In the second and third cases, caused by HSV, only the laryngeal mucosa is involved. Laryngeal symptoms, diagnostic criteria and therapeutic results are described. PMID- 8210096 TI - [Uncommon caseous maxillary sinusitis of dental origin caused by Microsporum canis]. AB - The authors report an uncommon case of maxillary sinusitis due to Microsporum canis. To their knowledge this is the first observation in which a zoophilic dermatophytic fungus which grows usually on keratin has been isolated in a dental maxillary sinusitis in human. This observation makes it possible to discuss nosologic and diagnostic features of dental caseous sinusitis and fungal sinusitis which are often or too often called aspergillosis sinusitis. PMID- 8210097 TI - [Lingual necrosis after neck irradiation]. AB - Lingual necrosis is a rarely observed pathology. The authors report a case of a lingual necrosis in the follow up of an irradiation. Horton's disease is the first diagnosis to evoke facing a lingual necrosis. This pathology is also one of the radiotherapy's complication, irradiation accelerates atherosclerosis process. An early treatment of this arterial complication can be proposed by a good prepossession and a doppler-pulse supervision of neck vessels. PMID- 8210098 TI - [Laryngostroboscopy]. AB - Videostroboscopy has become an essential examination for the assessment of vocal function. The authors describe and review the development of this technique with an analysis and discussion of its indications and results. PMID- 8210099 TI - [Pigmentation of ears, bedsores and rheumatic involvement: alkaptonuric ochronosis]. PMID- 8210100 TI - [Thomson-type congenital poikiloderma with reduced DNA repair capacity]. PMID- 8210101 TI - [Ichthyosis with neutral lipid storage: Dorfman-Chanarin syndrome. Apropos of a familial case]. PMID- 8210102 TI - [Congenital aggressive fibromatosis]. PMID- 8210103 TI - [Infantile aggressive fibromatosis (desmoid fibromatosis)]. PMID- 8210104 TI - [The neurofibromatosis-Noonan syndrome: 4 cases]. PMID- 8210105 TI - [Encephalo-cranio-cutaneous lipomatosis: a case]. PMID- 8210106 TI - [Acquired acrodermatitis enteropathica associated with lymphoma]. PMID- 8210107 TI - [Congenital cutaneous aplasia in the surviving monozygotic twin]. PMID- 8210108 TI - [Pretibial epidermolysis bullosa: a study in a family with lichenoid lesions]. PMID- 8210109 TI - [Localized pemphigoid after radiotherapy]. PMID- 8210110 TI - [Pemphigus vulgaris in a 18 month-old boy]. PMID- 8210111 TI - [Amicrobial pustulosis and systemic lupus erythematosus: a case]. PMID- 8210112 TI - [Dermatomyositis in childhood with recurrence in adulthood: 2 cases]. PMID- 8210113 TI - [Schnitzler syndrome with genetic C4 deficiency. 2 cases]. PMID- 8210114 TI - [Isolated purpura of the 4 limbs disclosing scurvy]. PMID- 8210115 TI - [Cutaneous vasculitis disclosing shunt nephritis]. PMID- 8210116 TI - [Cutaneous leukocytoclastic vasculitis with circulating anticoagulant disclosing myxoma of the left atrium]. PMID- 8210117 TI - [Cutaneous manifestations disclosing T-cell gamma/delta lymphoma in a 13-year-old girl]. PMID- 8210118 TI - [Epidermotropic T-cell gamma/delta lymphoma]. PMID- 8210119 TI - [Subcutaneous localizations of Burkitt's lymphoma at laparoscopic insertion sites]. PMID- 8210120 TI - [Plane xanthoma, chronic myelomonocytic leukemia, monoclonal gammapathy and anti lipoprotein activity]. PMID- 8210121 TI - [Diffuse amyloidosis: unusual buccal form and therapeutic trial with interferon alpha]. PMID- 8210122 TI - [Eosinophilic granuloma of the vulva]. PMID- 8210123 TI - [Febrile facial cellulitis: a severe and misleading case of acute neutrophilic skin disease in chronic myeloid leukemia]. PMID- 8210124 TI - [Cutaneous malacoplakia in heart transplanted patient]. PMID- 8210125 TI - [Cutaneous malacoplakia associated with chronic hepatitis caused by hepatitis C virus]. PMID- 8210126 TI - ["Gloves and socks" papulo-purpuric syndrome]. PMID- 8210127 TI - [Streptobacillus moniliformis: a rare anthropozoonosis sometimes observed in urban area]. PMID- 8210128 TI - [Multiple cylindroma in twin brothers]. PMID- 8210129 TI - [Congenital multiple cutaneous Abrikossof tumors]. PMID- 8210130 TI - [Dermatomyofibroma: a case in a child]. PMID- 8210131 TI - [Eruptive keratoacanthoma (the Grzybowski variety)]. PMID- 8210132 TI - [Multiple disseminated eruptive Spitz nevi: a case]. PMID- 8210133 TI - [Segmental neurilemmomatosis]. PMID- 8210134 TI - [Complete remission of cutaneous squamous cell carcinoma treated with interferon alpha and 2a-isotretinoin after failure of usual treatments]. PMID- 8210136 TI - [Epidermodysplasia verruciformis and eccrine syringoid carcinoma]. PMID- 8210135 TI - [Erysipelas-like eruption with hyperleukocytosis and fever: a new paraneoplastic syndrome in melanoma?]. PMID- 8210137 TI - [Erythema multiforme caused by Amphosept contact]. PMID- 8210138 TI - [Acral erythema occurring after didanosine (Videx) therapy]. PMID- 8210139 TI - [Retentive photosensitivity induced by chlorproethazine]. PMID- 8210140 TI - [Bullous drug eruption caused by Introna]. PMID- 8210141 TI - [Calciparin hypersensitivity reaction]. PMID- 8210142 TI - [Linear IgA dermatosis induced by penicillin G]. PMID- 8210143 TI - [Acute generalized exanthematous pustulosis induced by hydroxychloroquine]. PMID- 8210144 TI - [Male genital epidermolytic hyperkeratosis]. PMID- 8210146 TI - [Conjunctival lichen planus. A case]. PMID- 8210145 TI - [Mid dermal elastolysis: a case with a study of elastases]. PMID- 8210147 TI - [Early surgical treatment of eyelid angioma]. PMID- 8210148 TI - Capsular compliance: a measure of a "hard" prosthesis. AB - Capsular contracture prevents a natural "feel" to an augmented breast and is frequently a source of patient and physician dissatisfaction postoperatively. The degree of hardness of a breast is difficult to quantitate. We have developed a rodent model that measures the pressure rise in a capsule in response to increasing intraluminal volume, generating a pressure-volume curve. The curve's break point determines the volume contained within the capsule and the slope of the steep part of the curve to the right of the break point determines capsule resistance to stretch and deformation. In a group of 14 rats, resistance to distension increased progressively over a 14-week period whereas capsule surface area, break point volume, and resting intraluminal pressure remained relatively constant. This model allows the assessment of changes in capsule contracture over time without having to kill the animal. PMID- 8210149 TI - Radiation therapy as a cause of capsular contracture. AB - The effect of radiation therapy on the final result of breast reconstruction has been debated in the literature. We have had 4 patients with bilateral breast reconstruction who then received unilateral radiation therapy. We noted in all 4 that the irradiated side became contracted, whereas the nonradiated breast reconstruction remained soft. These 4 patients were compared with the bilateral breast reconstruction not receiving radiation therapy. The contracture rate in this control group was 10% (19 of 190 breasts). The difference in contracture rate between these two groups was significant (p = 0.05). A second group of patients was reviewed, unilateral reconstruction patients receiving radiation therapy to the reconstructed breast. This group was compared with bilateral reconstructions not receiving radiation therapy as a control group. The contracture rate in the unilateral reconstruction group receiving radiation therapy was 67% (7 of 11), versus the control of 10%. This difference is also significant (p = 0.001). We conclude that radiation therapy of prosthetic breast reconstruction does increase the rate of capsular contracture. Therefore, we counsel our implant reconstruction patients that the risk of capsular contracture is increased if subsequent radiation therapy is required. PMID- 8210150 TI - Diffusion of antibiotics across tissue expanders: an in vitro study. AB - Local infection remains a significant complication of tissue expansion. Subclinical infection of pockets with permanent prosthesis used in breast reconstruction has also been associated with capsular contracture around the implant. In an in vitro model, we used four groups of eighteen 50-ml tissue expanders, each containing Bactrim, Ancef, Nafcil, or saline only, in beakers containing fresh frozen plasma, placed in a rotary shaker for 48 hours. Inoculums of Staphylococcus aureus and Staphylococcus epidermidis were then selectively added to the medium external to the expanders in each group. The growth of such strains was found to be variably inhibited. We thus determined that antibiotics can diffuse through a tissue expander's Silastic membrane and establish an efficient bacteriostatic level in the surrounding fluid. This information could have potential clinical application in reducing infections associated with the use of expanders. PMID- 8210151 TI - von Willebrand's disease and plastic surgery. AB - Von Willebrand's disease (VWD) is the most commonly inherited coagulopathy. In a group of 1,000 plastic surgery patients, 8 or 9 individuals are affected by this disease, making basic knowledge of VWD and its management imperative. In this investigation, 1,000 plastic surgery patients were studied for details of their clinical evaluation, history of bleeding and bruising, and excessive bleeding during or after surgery. If the patient reported a history of easy bleeding or bruising, in addition to routine coagulation studies such as PT, PTT, and platelet count, the bleeding time was measured. When the index of suspicion dictated, more extensive coagulation studies, such as factor VIII assay, were conducted. This resulted in the detection of VWD in 9 patients (8 female and 1 male). All patients had a positive history of easy bleeding or bruising. Six of the 9 patients had a bleeding time greater than 6 minutes. Seven patients were diagnosed to have VWD type I, 1 had type II-a, and 1 suffered from type II-b disease. Perioperative bleeding was controlled in all patients in this study with the administration of 0.3 microgram/kg of body weight (usually a total dose of 20 micrograms) of 1-deamino-8-D-arginine-vasopressin intravenously every 12 hours for the first 24 hours. Two patients with type II VWD required fresh frozen plasma and cryoprecipitate 1 week subsequent to surgery to control late bleeding. PMID- 8210152 TI - Basic fibroblast growth factor has a beneficial effect on the viability of random skin flaps in rats. AB - We investigated the effect of exogenous basic fibroblast growth factor (bFGF) on the viability of random skin flaps in rats. Thirty-six rats were divided into three groups of 12 animals: a saline control group and two bFGF-treated groups. Caudally based random skin flaps were raised on the backs of the rats. In the control group, saline was instilled under the flap after skin closure. Twelve other rats were treated with bFGF (20 micrograms) just after skin closure. The remaining 12 rats were treated twice with bFGF (20 micrograms), both just after the operation and 48 hours later. There was a significant improvement in viability in the bFGF-treated groups on postoperative day 7 compared with the control group. Total adenine nucleotide levels in the flaps on postoperative day 10 were significantly higher in the group receiving two doses of bFGF than in the other groups. Thus, bFGF can improve the viability of endangered skin flaps. PMID- 8210153 TI - Improvement of skin flap perfusion by subdermal injection of recombinant human basic fibroblast growth factor. AB - The effect of subcutaneously injected recombinant human basic fibroblast growth factor (bFGF) was studied in an arterial skin flap model on the ear of the hairless mouse. Fifty-three male, hairless mice were randomly assigned to 4 groups and pretreated in two different time intervals with different doses of human bFGF. Microvascular perfusion of the skin flaps was determined over a 5-day period by means of intravital microscopy after intravenous injection of the fluorescence marker fluorescein isothiocyanate-dextran (M(r) 150,000). Human bFGF (2,700 ng) injected 6 days before flap creation could not improve perfusion of the flap (n = 10) when compared with controls. However, when applied 18 days before flap creation (n = 13), the same dose resulted in a significant reduction of nonperfused tissue at day 5 after flap creation (12.3% vs 26.8%, p < 0.01). Eighteen-day pretreatment with 1,200 ng (n = 10) and 480 ng (n = 10) had no significant effect on skin flap perfusion. We conclude, therefore, that successful pretreatment with bFGF for prevention of skin flap necrosis is time and dose dependent. PMID- 8210154 TI - The random upper posterior thigh fasciocutaneous flap. AB - A superiorly based random posterior thigh fasciocutaneous flap has evolved as a coexisting variant of the gluteal thigh composite flap, which is frequently important due to commonly encountered vascular anomalies in this region, such as absence of the descending branch of the inferior gluteal artery. This flap is distinguished by its reliance on the longitudinally oriented axis of the fascial plexus of the upper posterior thigh that is serviced predictably by multiple perforators from the cruciate anastomosis. In a series of 8 such flaps used in 7 patients over the past 10 years, only a single major complication has ensued. Therefore, it has proved to be of tremendous value as another simple, rapidly elevated option to close adjacent ischial or trochanteric defects; it supplements the other known flaps needed here because there is always a high risk of pressure sore recurrence. No muscle needs to be sacrificed, making this flap also a reasonable alternative for the ambulatory patient. PMID- 8210155 TI - Donor site deficit of the osteocutaneous radial forearm flap. AB - A functional evaluation was made of osteocutaneous radial forearm flap donor upper extremities at a mean 19.4 months postoperatively. Donor deficits were evaluated as follows: (1) skin: subjective appearance and durability; (2) skeleton: range of motion of adjacent joints; (3) vessels: cold intolerance, digital temperature, digital--brachial index; (4) muscle: key pinch; (5) nerve: two-point discrimination of dorsal first web space. Ten consecutive patients with a mean donor site area of 51.5 cm2 and mean length of harvested radius of 10.9 cm were studied. Incomplete skin graft take at the donor site (7 of 10 patients) and appearance of fair or poor (6 of 10 patients) were frequent cutaneous complications. Wrist range of motion was decreased with pronation (90%), flexion (90%), and extension (89%). Mean digital temperature, comparing extremities that did (operated) and did not (nonoperated) undergo surgery, or comparing the radial artery-supplied fingers to the ulnar artery-supplied fingers within the same operated hand showed no effect from the lost radial artery. Mean digital-brachial index was 1.24 for the nonoperated and 1.15 for the operated extremity. Key pinch on the operated side was a mean of 74% of the nonoperated side. Although raising the flap creates multiple tissue deficits, each with the potential to alter upper extremity function, detailed functional evaluation failed to demonstrate significant alteration in upper extremity function after flap harvest. PMID- 8210156 TI - Donor leg morbidity after pedicled rectus femoris muscle flap transfer for abdominal wall and pelvic reconstruction. AB - The pedicled rectus femoris muscle and myocutaneous flap has found application for a variety of soft tissue defects of the groin, pelvis, and lower abdomen. Although a number of authors have discussed the usefulness of this muscle flap, few have documented the morbidity from loss of this muscle in the leg. We have studied 7 patients who underwent unilateral rectus femoris muscle transfer, comparing strength of the donor knee to the normal knee. All patients were studied using a computerized dynamometer for strength of knee flexion and contraction. We found that loss of the rectus femoris in patients not undergoing a postoperative program of therapy led to an average decrease in strength about the knee of 24% to 28%, depending on the motion measured. A single patient who underwent an intensive postoperative therapy program had return of normal strength in his donor leg. Despite this common loss of strength, patient complaints were few and the results of reconstruction appeared to outweigh this loss of strength. PMID- 8210157 TI - The "L" reduction mammoplasty. AB - In the breast reduction technique presented, the nipple and areola are carried on a total breast tissue pedicle elevated from the pectoral fascia. Breast tissues are resected inferior to the areola and from the pectoral aspect of the breast. The residual breast tissues are left in continuity with the nipple. Final repair is done with a medial triangular and a lateral rectangular flap. The resulting scar is "L" shaped without a medial component. The technique is applicable for breast reductions, equalizations, and mastopexies. The operation is safe, leaves satisfactory inconspicuous scars, and carries a very low incidence of complications. PMID- 8210158 TI - The medial approach to the sural vessels to facilitate microanastomosis about the knee. AB - Complex wounds about the knee in rare instances may justify the selection of a distant microvascular tissue transfer for coverage. A major preoperative consideration then is the choice of an appropriate recipient site for revascularizing the flap that is outside the zone of injury, and preferably avoids the need for vein grafts. In many cases, the heads of the gastrocnemius muscles have protected the sural vessels from injury, allowing these to be used as a vascular extension of the popliteal system to simplify the required microanastomoses in an end-to-end fashion. Access to the sural vessels can be readily achieved through a medial approach to the popliteal fossa that permits the patient to remain supine or lateral on the operating table for simultaneous exposure of multiple privileged donor sites. PMID- 8210159 TI - Argon-pumped tunable dye laser. AB - The argon-pumped tunable dye laser (APTDL) is useful in the treatment of a wide variety of superficial vascular and melanocytic lesions. Safety is enhanced by the use of a computerized scanning device--the Hexascan. Over a 1-year period, 140 patients (33 patients under the age of 21, and 21 patients from 0 to 10 years of age) were treated. Facial rosacea/telangiectasia was the most frequently treated lesion, followed by port-wine stain. Although multiple treatments were often necessary, fading was successfully achieved in most patients without scarring or other complications. PMID- 8210160 TI - Some biomechanical considerations in microsutures. AB - The purpose of this study was to measure the biomechanical performance for commercially available microsutures, nylon polypropylene, polyester, and polyglactin 910. The biomechanical performance was determined by reproducible, biomechanical parameters that included stiffness, elasticity, resistance to creep, secure knot construction, and knot breaking strength. On the basis of these comprehensive studies, the handling characteristics of the nylon microsutures were judged to be superior over the other microsutures. Knot security was achieved with a three-throw square (1 = 1 = 1) knot that allowed a preview of the ultimate apposition of the divided tissue. In addition, nylon microsutures were more supple than the other microsutures. The breaking strength of the knotted nylon microsutures was comparable with those of the knotted polyglactin 910 and polyester microsutures, and significantly greater than that of the knotted polypropylene sutures. Its resistance to creep was significantly greater than that of the polypropylene microsutures but less than those of polyglactin 910 and polyester microsutures. PMID- 8210161 TI - An improved injection system for vascular anatomical studies having dual radiopacity and visualization capabilities. AB - An improved injection system, having both radiopacity and color, based on an emulsified solution of lead oxide, mineral oil, Triton X-100, and Tris buffer, has been developed and demonstrated in rats to possess superior qualities of injectability and to allow easy visualization of vascular elements to microscopic vessels in radiography and color and black-and-white photography. PMID- 8210162 TI - Indefinite survival of human skin allografts in patients with long-term immunosuppression. AB - The transplantation of a sufficient quantity of good quality skin is of great clinical importance. Severe burn patients lack adequate skin donor sites to cover their wounds with autografts. Patients with severe injuries and burns of areas such as the entire face are presently reconstructed with multiple full- or split thickness skin grafts. The final result is a patchwork appearance of skin with inferior qualities to normal full-thickness facial skin. Before structures such as hands should be transplanted, each individual tissue component should be evaluated to determine whether the tissue will survive and function with immunosuppression. Skin is obviously an important part of the hand. One hypothesis tested is the ability of transplanted human skin to survive indefinitely with long-term immunosuppression. The early detection of rejection of transplanted organs is paramount in reversing the rejection phenomena and hence saving the transplanted organ. Another hypothesis tested is the ability of a synchronously placed, same-donor, same-recipient skin graft to be used to detect rejection of a transplanted organ. As the skin and kidney from the same donor have similar antigens and the transplantation of both these tissues is to the same recipient and immunological system, it is hypothesized that there will be a correlation of rejection between the transplanted skin and the transplanted organ. To test the above hypotheses a small skin graft was placed on renal transplant patients synchronously with renal transplantation. The skin allografts were followed by direct observation and biopsy at regular intervals and at the time of suspected rejection. The patients were treated with the usual renal transplant immunosuppressant drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210163 TI - Vitamin A-soaked gelfoam sponges and wound healing in steroid-treated animals. AB - Previous work has shown improved wound healing after the administration of systemic vitamin A in patients on chronic steroids. In contrast there have been mixed reports on the effect of topical vitamin A on wound healing in steroid treated patients. Previous laboratory work has suggested that the topical application of vitamin A may be beneficial to wound healing in a sutured wound in a steroid-treated rat. Due to some inconsistencies in previous studies and steroid animal models, we sought to develop a better wound-healing model in a steroid-treated rat and to assess the effect of topical vitamin A as part of the wound closure. With preliminary studies, we developed a consistent and reliable wound-healing model in a steroid-treated rat using dexamethasone in contrast to cortisone acetate, which had been used in previous studies. Next, rats were randomized into 8 groups, some of which received steroids. Wounds were treated with saline or vitamin A topically or via a soaked gelfoam sponge. Rats were wounded 1 week after the commencement of steroid administration. Wounds were repaired and allowed to heal for 2 weeks. Strips of the wounds were then harvested and tested for tensile strength and breaking strength using a tensiometer. Wound edges were then fixed and wound surface area was measured using digital planimetry. Steroid treatment resulted in consistent weight loss and failure to gain weight as well as decreased breaking strength. Tensile strength was not decreased. Vitamin A applied for 10 minutes before wound closure and a gelfoam sponge alone placed before wound closure both resulted in an increased breaking strength and tensile strength.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210164 TI - Latex allergy: an intraoperative hazard. AB - First described in 1979, immediate hypersensitivity to latex has been occurring with increasing frequency. Though it has not been reported in the plastic surgery literature, hypersensitivity to rubber can present in the operating room with symptoms that range from mild urticaria to frank anaphylactic shock. Frequent contact with latex products appears to predispose certain groups to hypersensitivity. Diagnostic testing is not yet standardized and, when latex allergy is suspected, referral to an allergist is appropriate. Hypersensitive patients may be operated on safely with premedication and avoidance of latex products. PMID- 8210165 TI - Anteromedial thigh: a source for phallic reconstruction. AB - The anteromedial thigh region is a fruitful site to create different types of fasciocutaneous flaps and compound flaps because of its versatile fasciocutaneous vascularization. On the other hand, phallic reconstruction is still a challenge. We used a proximally based, fasciosubcutaneous pedicle anteromedial thigh fasciocutaneous flap to reconstruct a penis for an electrical burn patient, including the gracilis muscle into the flap for additional bulk. This flap has the potential for sensory reinnervation, its application is easy with regard to a microvascular operation and it presents a remarkable option in phallic reconstruction. PMID- 8210166 TI - Traumatic self-inflicted bite with embedded tooth fragments in the lower lip. AB - An unusual case of traumatic self-inflicted bite of the lower lip in a 7-year-old girl is presented. As a result of the bite, due to a fall, four fragments of the right upper incisor tooth were embedded in the lower lip. The large tooth fragment appeared 18 days later, protruding through the skin of the lower lip. Radiographs confirmed the presence of these tooth pieces, which were removed under local anesthesia. Early diagnosis and surgical removal of the tooth fragments could prevent undesirable foreign-body reactions and scarring. PMID- 8210167 TI - Symptomatic lacrimal duct diverticulum associated with closed nasal fracture. AB - Diverticula of the nasolacrimal collecting system are rare. Their cause may be congenital, inflammatory, or traumatic. A diverticulum of the nasolacrimal duct that presented 26 years after nasal trauma is described. The location of this diverticulum is extremely uncommon, and a case occurring after closed nasal trauma has not yet been presented. Evaluative studies and pertinent anatomy are reviewed. In any patient with recurrent dacryocystitis after nasal fracture, the diagnosis of a lacrimal system diverticulum should be considered. A detailed history and physical examination combined with dacryocystography can be confirmatory. Treatment should consist of surgical exploration with a nasolacrimal system bypass procedure. PMID- 8210168 TI - Dermatofibrosarcoma with lymph node involvement. AB - Dermatofibrosarcoma protuberans is a slow-growing, locally aggressive, fibrous tumor that, on rare occasions, metastasizes to distant sites or regional lymph nodes. We have found 28 patients with metastasis in the literature; 9 of these patients had lymph node metastasis. In this report we present a case of dermatofibrosarcoma protuberans of the lower extremity with metastasis to inguinal lymph nodes appearing 10 months after wide excision and skin grafting of the primary lesion. The clinical and pathological features of this case are presented. Although, along with our patient, 10 cases of regional lymph node metastasis are not justification for regional lymph node dissections, they do emphasize the need for regional lymph node examinations in the long-term follow up of dermatofibrosarcoma protuberans cases. PMID- 8210169 TI - Reconstruction of cryptotia using a skin graft. AB - Many surgical methods have been reported for the reconstruction of cryptotia. We have devised a new modified method for surgical correction of cryptotia that uses a skin graft from the retroauricular region, and have treated 15 ears of 14 patients using this method. The method is described and cases are illustrated. PMID- 8210170 TI - Up in arms. PMID- 8210171 TI - Development of motoneuronal phenotype. PMID- 8210172 TI - The early reactions of non-neuronal cells to brain injury. PMID- 8210173 TI - The subplate, a transient neocortical structure: its role in the development of connections between thalamus and cortex. PMID- 8210174 TI - Synaptic vesicles and exocytosis. PMID- 8210175 TI - The epigenetics of multiple sclerosis: clues to etiology and a rationale for immune therapy. PMID- 8210176 TI - Neuronal polarity. PMID- 8210177 TI - Cloned glutamate receptors. PMID- 8210178 TI - Prion diseases and neurodegeneration. PMID- 8210179 TI - Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function. PMID- 8210180 TI - Determination of neuronal cell fate: lessons from the R7 neuron of Drosophila. PMID- 8210181 TI - Molecular basis for Ca2+ channel diversity. PMID- 8210182 TI - Specification of neocortical areas and thalamocortical connections. PMID- 8210183 TI - Direct G protein activation of ion channels? PMID- 8210184 TI - The anatomy and physiology of primate neurons that control rapid eye movements. PMID- 8210185 TI - Normal and abnormal biology of the beta-amyloid precursor protein. PMID- 8210186 TI - Organization of memory traces in the mammalian brain. PMID- 8210187 TI - The protein kinase C family for neuronal signaling. PMID- 8210188 TI - [Conservative rhinoplasty]. AB - In most reduction rhinoplasties, conservative rhinoplasty of the nasal roof and septum can be performed in the place of traditional rhinoplasty with resection of the hump. An anatomical and functional study of the nose justifies and explains this new surgical technique. However, impaction alone is not always sufficient, but, in some cases, must be combined with support or projection of the nose tip. In the rhinoseptoplasty proposed, the nasal roof phase is performed before the nostril roof phase. The advantages of this technique, particularly indicated in kyphosis, are related to the preservation of the natural appearance of the nose and its persistence over time. PMID- 8210189 TI - [Median and paramedian orbito-facial clefts: value of the L-shaped incision in the surgical treatment of nasal deformities]. AB - Authors have reported an interest in the latero-nasal incision for surgical treatment of nasal deformities of patients with median and paramedian orbito facial clefts. Validity of this "L" approach is correlated to its respect for the integrity of aesthetic facial units and to its position in a natural fold (naso labial fold). A series of patients with median and paramedian orbito-facial clefts were operated upon using this approach and good results were obtained which support its theoretical value. PMID- 8210190 TI - [Nasolabial flap in the repair of partial transfixing loss of substance of the nostril]. AB - The nasolabial flap has frequently been used in many ways to repair the nostril. It has also been the subject of numerous criticisms, essentially related to the poor quality of the results obtained. However, the authors consider that it has an important place in the treatment of partial transfixing defects of the nostril. The nasolabial flap must be performed according to certain precise rules: strictly nasal superior pedicle, defatting of the entire flap, rotation of the flap around the external extremity of the pedicle, plication of the flap and modelling to recreate the alar margin and to reconstitute the lining. Several clinical examples illustrate this use of the flap and allow the indications to be defined. PMID- 8210191 TI - [Reversed vascular full-thickness nasolabial flap]. AB - The author describes a vascular island full-thickness nasolabial flap, which is superior pedicled and is nourished by the distal portion of axial vessels, the facial artery and vein, by means of a reverse blood flow. When the vein is not available, a muscular pedicle can provide the venous drainage. This composite musculo-mucocutaneous flap was used in a single stage procedure for external cover and internal lining repair in 32 cases of full-thickness defect of the alar lobule (18 cases) or of the lower half of the nasal sidewall (14 cases). Some cases needed a secondary defatting (37.5 per cent). The final result was good in all cases, with minimal sequelae on the donor site. PMID- 8210192 TI - [Total reconstruction of the nose by osteocutaneous preformed forearm flap. Apropos of a case]. AB - The authors report the case of a 28-year-old woman in whom multiple surgical reconstructions were performed to cure an extensive radiation necrosis of the nose. In 1980, after the failure of a dorsalis pedis free flap and of a free groin flap, success was obtained with a free lateral mammary flap. But defatting, bone grafting and modelling produced partial necrosis of the flap. Finally, total nasal reconstruction was achieved in 1983 with a pedicled osteocutaneous forearm flap. To secure the transfer, the flap was first modelled by folding directly on the donor site. The advantages of this procedure are a lower risk of postoperative infection and a fewer number of secondary surgical stages needed to achieve the reconstruction. The reliability of the forearm flap and the simplicity of the procedure advocate its use in difficult reconstructions of the nose, when others techniques could not give better results. PMID- 8210193 TI - [History of medicine. Resection of tumors of the nose]. PMID- 8210194 TI - ["CAB" (Corpus Adiposum Buccae). Anatomical description and surgical reflexions apropos of buccal fat pads]. AB - Thirty hemi-faces of fresh cadavers and two centuries of bibliographies have been studied. Both packed fat and organ fat linked to the mastication, the Corpus Adiposum Buccae (CAB-Bichat's fat ball) is an anatomic structure which involves the entire hemi-face. The CAB stretches from the temporal region to the cheek, passing through the zygomatico-malar tunnel and the pterygomandibular fossa. It is completely enclosed within a partitioned capsule of varying thickness which allows to recognise it. From its main part, the Body, the CAB has ten extensions. Size, volume and aspect are different from one subject to another and one side to another. Its cheek extensions are inconsistent or disappear with age. However, its outline remains characteristic. This is not a ball one except in the case of the foetus and new born and for the most sloping extension, buccal, which gives its name to CAB. The CAB is always found under the SMAS plane which keeps it apart from superficial fat. Where fronto-facial liftings are more extensive and deeper, the CAB becomes an important surgical reference. It is possible to use the CAB as a local flap for filling in the cheek area. Local partial amputations have been put forward as an aesthetic goal. In the light of the present study, the author suggests a discussion with regards to the validity of these surgical manipulations. PMID- 8210195 TI - [Launois Bensaude disease. Focus apropos of 16 cases]. AB - After a review of the clinical, pathological and aetiological features, the authors describe the various surgical techniques used (conventional surgery or liposuction) to restore a normal social life to these patients, deformed by their disease. They confirm the predominant role of conventional surgery and define the limited indications in which liposuction can be used. Based on a review of 16 cases, the surgeon must make sure that the patient has ceased his or her alcohol abuse before performing this difficult treatment associated with a number of complications. PMID- 8210196 TI - [Liposuction in the plastic surgery of the abdomen. Focus on technical aspects and indications]. AB - The contribution of liposuction has transformed the plastic surgery of the abdomen, by allowing to broaden the indications and by improving a great deal the quality of the results. The most delicate question in this field and in a large number of the cases comes down to making a choice between an isolated abdominal liposuction and an abdominal liposuction associated to a cutaneous reduction plasty. Our experience during these last years has shown us that very good results in isolated abdominal liposuction could be achieved even in patients whom skin elasticity tests were fairly favourable. These results encourage us to broaden markedly the indications of isolated abdominal liposuction, even in intermediate or borderline cases: it is necessary though, to perfectly inform the patient with whom we have a true confidence agreement, even if it means in some cases a second surgical procedure: either a complementary liposuction or a secondary cutaneous reduction plasty. PMID- 8210197 TI - [Internal breast support grids in the surgery for breast hypertrophy and ptosis. Technique and indications]. AB - In breast surgery, the use of a Grade for Internal Support of the Mamma (GISM) is an elegant way to reduce the length of the scars as it becomes possible to conserve only the peri-areolar incision. The technique has been imagine by Bustos in 1985. Its principles are: the reshaping of the gland with a posterior pedicle; the use of a silicone sheet that supports the gland; the spontaneous adaptation of the skin over the reshaped breast. A new sheet (GISM) is presented allowing a modification of the Bustos's technique that becomes easier and shorter. Technique and indications are described, and results are analysed. PMID- 8210198 TI - [Microsurgical expanded musculocutaneous flaps of the latissimus dorsi]. AB - Four successful cases of expanded free latissimus dorsi myocutaneous flaps are reported. Expansion of free latissimus dorsi flaps has 2 distinct advantages: moulding of the flap prior to its transfer to a convex surface (cranium); primary closure of the donor site. The latissimus dorsi myocutaneous flap seems to be the flap of choice for pre-transfer expansion. PMID- 8210199 TI - [Free latissimus dorsi flap revascularized by double venous graft on the femoral trifurcation in the treatment of lumbar radionecrosis. Apropos of 2 cases]. AB - Two patients were operated in 1989 and 1992 for lumbar chronic osteoradionecrosis (toxi-infection collapsus in one of the two cases). Conventional coverage procedures (skin graft, local flaps) or distally based latissimus dorsi musculo cutaneous flap (second case) were attempted but failed. So we realised in a one stage procedure a free musculo-cutaneous flap in the case no. 1 and a free muscular flap, later skin grafted, in the case no. 2. Venous and arterial bypass were provided by 40 cm long saphenous veins harvested from the thighs, and allowed to reach the lumbar site with proximal anastomosis performed on the femoral artery. The results were considered to be excellent. That short experience shows that long venous bypass with microsurgical free transfer can be safely performed. This results in an extremely high flow shunt. PMID- 8210200 TI - [Comparative study of various treatment methods of mucoid cysts of the fingers]. AB - 100 mucocysts were reviewed in 93 patients. Surgical removal was done in 66 cases, associated with an osteophytectomy in 38 cases (57 p. cent). Among the 5 recurrence observed (7.6 p. cent), 3 occurred after simple excision, 2 occurred after associated osteophytectomy. PMID- 8210201 TI - [Patents and innovations. Definitions--modes of action]. AB - The author presents the various methods available for the doctor to protect and exploit his inventions or technological discoveries. In the medical field, as in other fields, there are three titles of industrial property: patent, registered model and trademark. The modalities of each of these titles are explained. Based on the his own experience, the author presents advice concerning the use of patents, contracts and the choice of industrial partners. PMID- 8210202 TI - [Reflexions on the treatment and outcome of burns]. PMID- 8210204 TI - [A hydatid cyst of the head of the pancreas causing a fistula into the duodenum. Apropos of a case]. PMID- 8210203 TI - [Ultrasonographic data of the solid organs of the abdomen in stage IV human immunodeficiency virus infection. A prospective study of 101 cases in central Africa]. AB - A systematic abdominal study of the solid organs of the abdomen (liver, spleen, pancreas, kidneys) carried out in one hundred patients from Central Africa suffering from full blown AIDS revealed disseminated hyperechoic liver in 37 cases and hypoechoic nodules of the spleen in 10 cases. The combination with abdominal adenopathy and/or serous exudates (peritoin, pleura, pericardium) suggested disseminated tuberculosis. Twenty of the 37 patients with diffusely hyperechoic liver presented within tuberculosis which was confirmed by bacteriological data (AARB present in the sputum) in 13 cases. Of the 10 patients presenting with hypoechoic nodules of the spleen, 5 presented with confirmed tuberculosis. These 10 patients were all considered to have disseminated tuberculosis. In view of the current high incidence of extrapulmonary or disseminated tuberculosis occurring in a context of AIDS and the relative infrequency of positive tests for Mycobacterium, abdominal ultrasound must be coupled with chest X-rays in screening and prompt follow-up for TB instigated in HIV-positive adult Africans. PMID- 8210205 TI - [Vaccination against the enterobacteria responsible for enteric infections]. AB - Development of vaccines against enterobacterial species responsible for enteric infections sounds like an unrealistic project. On the other hand, based on our growing understanding of the pathogenesis of infections caused by the major species (i.e. Salmonella typhi, Shigella flexneri and Shigella dysenteriae 1, Enterotoxigenic Escherichia coli) and on our better characterization of the immunological parameters of mucosal protection, it is likely that a limited number of vaccines controlling diseases such as typhoid fever, bacillary dysentery and cholera-like E. coli infections will become available. There are three major problems that still need to be solved: the variety of antigens and antigenic specificities, the nature of protective antigens and, provided that these prerequisites are fulfilled, the presentation of the vaccine and the immunization route. With the exception of typhoid fever, which has a systemic phase that probably makes immunization attempts by purified Vi antigen successful, experimental strategies rely very much on induction of a mucosal immunity. Either subunit vaccines, or genetically manipulated strains which attenuated virulence are currently considered. PMID- 8210206 TI - [Intercellular communications in cell differentiation and in hepatic carcinogenesis]. AB - The liver epoch like other tissue epochs occurs after that different events have induced heterogeneity in embryonic cells which results in distinct evolutionary processes. These events and those of organogenesis like "induction" are deeply dependent on cell-cell communications. Cell-cell interactions involve either soluble factors (hormones, growth factors), extracellular matrix or plasma membrane proteins responsible for cell-cell recognition and/or adhesion. All these plasma membrane signals are transduced to the nucleus and modulate the expression of groups of genes. To be functionally stable along the adult stage the liver has to maintain an ordered activity of cell renewal. This balance between proliferation and differentiation is, at least in part, controlled by cell-cell communications. Therefore, it is not surprising that intercellular communications are altered during hepatocarcinogenesis. They involve changes in the distribution of junctions, in the amounts of extracellular matrix components and/or growth factors which all result in modifying the differentiation/proliferation balance. Cell culture models have been used for these different studies; new in vitro systems should be set up in the near future by taking advantage of the targeted hepatocarcinogenesis in transgenic mouse. PMID- 8210207 TI - [The treatment of ureteroceles complicated by calculi]. AB - In a series of 13 adults with calculi in ureteroceles, 10 cases underwent endoscopic meatotomy associated with endoscopic lithotripsy. In 2 bulky ureteroceles with calculi, the authors performed excision of the ureterocele and reimplantation of the ureter. In one case, the authors successfully performed extracorporeal lithotripsy. The authors obtained good results in all cases. Endoscopic meatotomy with lithotripsy is a very useful procedure for treatment of small or medium sized ureteroceles with calculi in adults. PMID- 8210208 TI - [Calculous anuria. Apropos of 63 cases]. AB - Sixty-three cases of anuria secondary to renal stones were treated in the Sfax urology department between 1982 and 1990. The presenting symptoms are frequently polymorphic and non-specific. The prognosis of these patients largely depends on the infectious complications associated with anuria, the delay in management and, most importantly, the course of preexisting renal failure. Fifteen deaths (24%) were observed in this series, despite emergency urinary diversion and appropriate treatment to eliminate the obstruction. PMID- 8210209 TI - [Ureteral calculi]. PMID- 8210211 TI - [Obstructive calculus of the lumbar ureter treated by extracorporeal shock wave lithotripsy (ESWL)]. PMID- 8210210 TI - [Clinical tests on reno-ureteral lithiasis with a new Lithostar 2 model C shock wave generator system]. AB - Lithotripsy has confirmed its place in the treatment of urinary stones and there are now few indications for open surgery in this disease. Lithotripsy used to be rarely used, as it required a great deal of patience on the part of the patient, lying in the water bath, and the medical team. Increasing efficient systems are now available with a marked advantage for patients. Simple analgesia-sedation is often sufficient when requested by the patients and the duration of treatment has been considerably decreased. The authors present a review of their results with the new Lithostar 2 Model C shock wave generator system. The modifications made to this system take into account physical possibilities and medical requirements. As a result of the new configuration of this system, the treatment time per patient has been further decreased, a higher energy is applied to the stones and the disintegration rate is excellent. PMID- 8210212 TI - [Treatment of a ureteral calculus trapped in a ureterocele sac using the overhead module Lithostar C]. PMID- 8210213 TI - Ureterorenoscopy for ureteral stones. Still current? PMID- 8210214 TI - [A Calcutript-Lithoclast comparison: electrohydraulic lithotripsy versus acoustic pressure wave lithotripsy. An in vitro study on chalk cubes]. AB - Intracorporeal lithotripters are available in nearly all urological institutions. The authors compared the CALCUTRIPT made by K. Storz Co. and the Swiss LITHOCLAST in in vitro studies. No major difference in the efficacy of disintegration was observed after subjecting chalk cubes to the two modalities. Human tissue of the renal pelvis, ureter and bladder was exposed to both energy-sources. In the case of the electrohydraulic shock wave the authors found complete rupture of all three layers of the ureteric wall after exposure even with low energy, while tissue perforation was observed in only one of 72 tissue samples exposed to the LITHOCLAST. The authors recommend the LITHOCLAST because of its minimal invasiveness for the treatment of calculi especially in the ureter. PMID- 8210215 TI - [The role of Lithoclast in the endo-urologic treatment of urinary calculi (kidney and ureteral)]. AB - The authors report their experience of the use of the Lithoclast in endocorporeal lithotripsy in 19 patients. This modality allowed the fragmentation of 24 renal stones and 14 ureteric stones with complete success in 58% of cases and partial success in 42% of cases. No failures of stone fragmentation were observed in this series with the Lithoclast. The authors consider this apparatus to be an effective and inexpensive method of endocorporeal lithotripsy for all types of urinary stones. PMID- 8210216 TI - [Problems in the clinical evaluation of an endoscopic lithotripter. The case of the Lithoclast EMS]. AB - The rapid appearance of various clever and efficient techniques for fragmenting urinary stones in the past 10 years, and their often combined use, makes an objective evaluation of an intracorporeal lithotripter impossible since the criss cross of the factors to be considered is very important in the literature. Two University Hospitals, one in France (Paris), the other in Germany (Bochum-Herne) have agreed upon a common protocolic, making a coherent and numeral evaluation possible, derived from two different and independent spheres. After a methodological introduction, the results of the research concerning the EMS Lithoclast are reported. PMID- 8210217 TI - [The treatment of ureteral calculi. Open surgery retains a few indications]. PMID- 8210218 TI - [From shock-waves even to ureterolithotomy: various practical cases]. AB - The Puigvert Urology Centre in Barcelona reports the detailed results of five cases of ureteric stones all treated by first-line shock wave lithotripsy. Only one case obtained a positive result (after 4 sessions). In the other four cases, shock wave therapy had to be completed by ureteroscopy (1 case) or by open surgery (3 cases) to achieve cure. PMID- 8210219 TI - Magnetic resonance imaging of brain function. PMID- 8210220 TI - The functional organization of the hippocampal dentate gyrus and its relevance to the pathogenesis of temporal lobe epilepsy. AB - Temporal lobe seizures are frequently associated with a characteristic pattern of hippocampal pathology (hippocampal sclerosis), as well as pathology in other temporal lobe structures. Despite more than a century of study, the relationship between pathology and epileptogenesis remains unclear. Endfolium sclerosis, which is characterized by the loss of dentate hilar neurons that are presumed to govern dentate granule cell excitability, is evident whenever hippocampal sclerosis exists and is the only temporal lobe pathology in some patients. Because prolonged seizures or head trauma produce endfolium sclerosis and granule cell hyperexcitability in experimental animals, hilar neuron loss may be the common pathological denominator and primary network defect underlying development of a hippocampal seizure "focus." Physiological studies suggest that vulnerable hilar mossy cells normally excite neurons that mediate granule cell inhibition. Recent anatomical studies indicate that the axons of mossy cells project longitudinally, out of the lamellar plane in which their cell bodies lie. If mossy cells in one lamella excite inhibitory neurons in surrounding lamellae, neocortical excitation of one segment of the granule cell layer may produce lateral inhibition and limit neocortical excitation to the targeted lamella. In patients who have had status epilepticus, prolonged febrile seizures, head trauma, or encephalitis, loss of dentate mossy cells may deafferent inhibitory neurons, render them "dormant," and thereby disinhibit an enlarged expanse of the granule cell layer. The selective loss of neurons that normally govern lateral inhibition in the dentate gyrus may cause functional delamination of the granule cell layer and result in synchronous, multilamellar discharges in response to cortical stimuli. Repetitive seizures may ultimately produce the full pattern of hippocampal and mesial temporal sclerosis by destroying cells within the seizure circuit that were not injured irreversibly by the initial insult. Thus, hippocampal pathology may be both the cause and effect of seizures that originate in the temporal lobe. PMID- 8210221 TI - Antiparkinsonian effects of remacemide hydrochloride, a glutamate antagonist, in rodent and primate models of Parkinson's disease. AB - Loss of dopaminergic innervation of the striatum results in overactivity of the glutamatergic pathways from the subthalamic nucleus to the internal segment of the globus pallidus and the substantia nigra pars reticulata, the output nuclei of the basal ganglia. Previous work has shown that local blockade of glutamate receptors in the internal segment of the globus pallidus or substantia nigra pars reticulata leads to marked suppression of parkinsonian signs. We have now examined whether systemic administration of a glutamate receptor antagonist has antiparkinsonian effects in rodent and primate models of Parkinson's disease. Remacemide hydrochloride is an anticonvulsant, neuroprotective compound with antagonist activity at the N-methyl-D-aspartate receptor ion channel. In normal rats and monoamine-depleted rats, remacemide hydrochloride did not cause locomotor hyperactivity, unlike MK-801. When monoamine-depleted rats were treated with a subthreshold dose of levodopa methylester, remacemide hydrochloride (5-40 mg/kg, orally) caused a dose-dependent increase in locomotor activity. Moreover, remacemide hydrochloride (10 mg/kg, orally) potentiated the effects of each suprathreshold dose of levodopa methylester tested (100-200 mg/kg, intraperitoneally). Parkinsonian rhesus monkeys were tested with oral doses of vehicle plus vehicle, vehicle plus levodopa-carbidopa, and remacemide hydrochloride (5 mg/kg) plus levodopa-carbidopa. Blinded clinical scoring of videotapes revealed that treatment with remacemide hydrochloride plus levodopa carbidopa was substantially better than levodopa-carbidopa plus vehicle or vehicle plus vehicle. The effects of remacemide hydrochloride lasted at least 5 hours. We conclude that certain N-methyl-D-aspartate receptor antagonists have antiparkinsonian actions and low potential for side effects. Clinical trials of remacemide hydrochloride in patients with Parkinson's disease may be warranted. PMID- 8210222 TI - Functional magnetic resonance imaging of human auditory cortex. AB - Magnetic resonance imaging methods recently demonstrated regional cerebral signal changes in response to limb movement and visual stimulation, attributed to blood flow enhancement. We studied 5 normal subjects scanned while listening to auditory stimuli including nonspeech noise, meaningless speech sounds, single words, and narrative text. Imaged regions included the lateral aspects of both hemispheres. Signal changes in the superior temporal gyrus and superior temporal sulcus were observed bilaterally in all subjects. Speech stimuli were associated with significantly more widespread signal changes than was the noise stimulus, while no consistent differences were observed between responses to different speech stimuli. Considerable intersubject variability in the topography of signal changes was observed. These observations confirm the utility of magnetic resonance imaging in the study of human brain structure-function relationships and emphasize the role of the superior temporal gyrus in perception of acoustic phonetic features of speech, rather than processing of semantic features. PMID- 8210223 TI - Course and outcome of acute cerebellar ataxia. AB - We report a study of 73 consecutive children with acute cerebellar ataxia, representing all of the children evaluated at St. Louis Children's Hospital during a 23-year-period to whom this diagnosis could appropriately be assigned. Twenty-six percent had chickenpox, 52% had other illnesses that were presumed to be viral, and in 3% the ataxia was related to immunization. Nineteen percent had no definite prodrome. Sixty children were followed for 4 months or longer after onset of their ataxia (mean, 7.4 +/- 6.0 years). Ninety-one percent (55/60) of these, including all children with chickenpox, recovered completely from ataxia. Eighty-nine percent (39/44) of the children with non-varicella-related ataxia recovered completely from the ataxia, a much better rate of recovery than what was found in prior large studies. One fifth of the children followed for more than 4 months experienced transient behavioral or intellectual difficulties, but only 5 of the 60 children demonstrated sustained learning problems. This study represents the largest reported series of acute cerebellar ataxia and the most complete characterization of the clinical features and outcome of this illness. PMID- 8210224 TI - Methylmercury poisoning: long-term clinical, radiological, toxicological, and pathological studies of an affected family. AB - For 3 months in 1969 a family in the United States that included a pregnant mother consumed pork containing methylmercury. Children, aged 20, 13, and 8 years and a neonate, developed severe neurological signs. Twenty-two years later, the 2 oldest had cortical blindness or constricted visual fields, diminished hand proprioception, choreoathetosis, and attentional deficits. Magnetic resonance images showed tissue loss in the calcarine and parietal cortices and cerebellar folia. The youngest had quadriplegia, blindness, and severe mental retardation until their deaths. The brain of the 8-year-old who died at age 30 showed cortical atrophy, neuronal loss, and gliosis, most pronounced in the paracentral and parietooccipital regions. The total mercury level in formalin-fixed, left occipital cortex was 1,974 ng/gm as measured by atomic absorption. Regional brain mercury levels correlated with extent of brain damage. A control patient had 38.5 ng of mercury/gm in the occipital cortex. Systemic organs in the patient and a control subject had comparable mercury levels. In mercury-intoxicated rats, we found that only 5 to 10% of total brain mercury was lost by formalin fixation. Brain inorganic mercury in the patient ranged from 82 to 100%. Since inorganic mercury crosses the blood-brain barrier poorly, biotransformation of methyl to inorganic mercury may have occurred after methylmercury crossed the blood-brain barrier, accounting for its persistence in brain and causing part of the brain damage. PMID- 8210225 TI - MRI detects acute degeneration of the nigrostriatal dopamine system after MPTP exposure in hemiparkinsonian monkeys. AB - Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can cause an acute chemical toxicity resulting in a parkinsonian state in humans and nonhuman primates. We wished to assess whether the toxicity from MPTP is associated with changes on magnetic resonance images of brain structures containing dopamine neuronal processes or with disrupture of the blood-brain barrier. Normal rhesus monkeys and monkeys at various times after being subjected to unilateral intracarotid injection of MPTP (0.4 mg/kg) were studied with magnetic resonance imaging using T1- and T2-weighted spin-echo and gradient-echo sequences. Disrupture of the blood-brain barrier was assessed also with magnetic resonance imaging after administration of gadolinium-diethylenetriamine pentaacetic acid. Parkinsonian symptoms contralateral to the infused carotid usually appeared within 1 day after MPTP exposure, reaching their peak severity by 7 days, when all monkeys showed clear clinical abnormalities. Magnetic resonance imaging changes developed in concomitance with the clinical signs and were characterized by increased signal intensity on T2-weighted images as well as decreased intensity on T1-weighted images of the ipsilateral caudate and putamen. T2 hyperintensity was also present just dorsal to the pars compacta of the substantia nigra, in the region of the proximal nigrostriatal tract. All magnetic resonance imaging changes dissipated in the next 2 weeks. There were no abnormalities at any time in the globus pallidus, nucleus accumbens, and other structures innervated by the mesocorticolimbic dopamine system. After MPTP exposure, there was no evidence of blood-brain barrier disrupture, suggesting that vasogenic edema was an unlikely factor in the production of the observed abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210226 TI - Monoclonal IgM antibodies to GM1 and asialo-GM1 in chronic neuropathies cross react with Campylobacter jejuni lipopolysaccharides. AB - We tested monoclonal IgM anti-GM1 and asialo-GM1 antibodies from 6 patients with chronic motor neuropathies for binding to lipopolysaccharides (LPS) from three stains of Campylobacter jejuni. Four of the 6 patients showed strong reactivity with LPS from at least one of the three C. jejuni strains tested as shown by enzyme-linked immunosorbent assay or western blot. Preabsorption with GM1 or asialo-GM1, or blocking with cholera toxin, prevented antibody binding to LPS. These studies indicate that human anti-GM1 or anti-asialo-GM1 antibodies cross react with LPS from certain strains of C. jejuni, and that bacterial LPS might provide antigenic stimuli for the activation of B cells expressing anti-GM1 antibodies. PMID- 8210227 TI - Deletion in the CMT1A locus on chromosome 17p11.2 in hereditary neuropathy with liability to pressure palsies. AB - Hereditary neuropathy with liability to pressure palsies (NHPP) is an autosomal dominant disease of peripheral nerves, characterized by recurrent focal neuropathies often with an underlying asymptomatic polyneuropathy. We report the clinical, electrophysiological, and histopathological findings in three families with HNPP and confirm the presence of a deletion on chromosome 17p11.2, including all the markers known to be duplicated in Charcot-Marie-Tooth disease type 1A. This deletion appears to be the underlying molecular deficit in this disease and provides additional evidence for the importance of this locus for peripheral nerve function. PMID- 8210228 TI - The prevalence of narcolepsy: an epidemiological study of the Finnish Twin Cohort. AB - We investigated the prevalence of narcolepsy using a well-defined white population previously used for epidemiological investigations: the Finnish Twin Cohort. The Cohort consists of 13,888 monozygotic and dizygotic twin pairs born before 1958. There were 16,179 individuals who participated in the study, with a 77.3% response rate. The study methodology included a questionnaire covering sleep and alertness, the Ullanlinna Narcolepsy Scale (UNS), a scale specifically developed and tested for the study, telephone interviews, and finally, clinical evaluation, polygraphic recording, and HLA blood typing. Seventy-five subjects were selected for telephone interviews and laboratory evaluations based on data from both questionnaires. Five of them were strongly suspected of narcolepsy, but laboratory data identified only 3. All were dizygotic (fraternal) twins discordant for the disease with a negative family history and presence of DR2 DQw1 (i.e., DRw15 DQw6, new World Health Organization classification). The prevalence of narcolepsy in the Finnish population is 0.026% (95% confidence interval, 0.0-0.06). This prevalence is lower than that reported in studies performed without polygraphic recording and is close to that reported in 1945 in the black U.S. population. The tools developed to perform this study, the largest population study of its kind yet performed, can now be used for other population investigations. PMID- 8210229 TI - The relationship of essential tremor to other movement disorders: report on 678 patients. Essential Tremor Study Group. AB - We examined 678 essential tremor patients in specialty, university, and private practice clinics. The mean age of patients was 65.2 years with a similar number of men and women. Six percent of patients were left-handed. A positive family history of tremor was reported in more than 60% of patients. Alcohol ingestion was reported to decrease tremor in 74% of patients who were cognizant of the effect of alcohol on tremor. Mean age at tremor onset was 45.3 years. An earlier onset of tremor was observed in those patients having a positive family history of tremor. Tremor affected the hands in 90% of patients, head in 50%, voice in 30%, and legs and chin in 15%. Functional disability was common and impairment at work occurred in 18%. Propranolol and primidone were the most frequently used drugs and were effective in 40% of patients. Six and one-tenth percent of essential tremor patients had concomitant Parkinson's disease, 6.9% had a coexisting dystonia, and 1.8% had myoclonus. It is concluded that the frequency of Parkinson's disease in essential tremor is more than would be reported in the general population and that other movement disorders are infrequently observed in essential tremor. PMID- 8210230 TI - Interictal spiking increases 2-deoxy[14C]glucose uptake and c-fos-like reactivity. AB - Although interictal spikes are thought to share pathophysiological mechanisms with partial-onset seizure discharges, positron emission tomographic studies of the interictal state have paradoxically shown focal hypometabolism whereas seizures produce hypermetabolism. To address this question, we performed functional mapping studies in an interictal spiking model in the rat. Recording screw electrodes were inserted through the skull bone so as to depress underlying cortex. Interictal spiking was subsequently induced by systemic administration of bicuculline methiodide. 2-deoxy[14C]glucose studies revealed increased glucose utilization in superficial and middle cortical layers at spiking screw sites. Nonspiking screw sites in the same animals and in controls did not show increased uptake. Convulsive seizures caused additional 2-deoxy[14C]glucose uptake at screw sites and in widespread forebrain areas. c-fos immunoreactivity occurred in superficial cortex at interictal spiking, but not nonspiking, sites. Convulsive seizures induced widespread forebrain c-fos immunoreactivity. These data suggest interictal epileptiform activity occurs in cells adjacent to cortical injury; these activate deeper layers via local connections. Interictal and ictal epileptiform states share common mechanisms, as both induce glucose hypermetabolism and immediate-early gene product activation. Possible reasons for failure to detect hypermetabolism in interictal human subjects are discussed. PMID- 8210231 TI - Brain morphology in normal and dyslexic children: the influence of sex and age. AB - Morphometric magnetic resonance imaging techniques were used to compare the convolutional surface area of the planum temporale, temporal lobe volume and superior surface area, and an estimate of overall brain volume in a homogeneous sample of 17 dyslexic children (7 girls) and 14 nonimpaired children (7 girls). Substantial sex differences were apparent for all measured regions, with all the measurements in boys being significantly larger. Age, even within the narrow range employed here (7.5-9.7 years), was positively correlated with the size of each brain region. While initial analyses suggested smaller left hemisphere structures in dyslexics compared to control subjects, subsequent analyses controlling for age and overall brain size revealed no significant differences between dyslexics and nonimpaired children on a variety of measures, in particular surface area and symmetry of the planum temporale. We suggest that differences in subject characteristics (i.e., sex, age, handedness, and definition of dyslexia) as well as procedural variations in the methods used to acquire images and to define and measure anatomical regions of interest such as the planum temporale all may play an important role in explaining apparent discrepant results in the neuroimaging literature on dyslexia. PMID- 8210232 TI - Seizure exacerbation and status epilepticus related to carbamazepine-10,11 epoxide. AB - Over a 3-year period, we encountered 6 adults whose seizure control unexpectedly deteriorated with the occurrence of partial status epilepticus and daily multiple seizures. Analysis of the case histories and subsequent clinical follow-up for 1 1/2 to 3 years disclosed the following evidence that demonstrates the role of carbamazepine-epoxide in the development of the seizure exacerbation: (1) There were high serum carbamazepine-epoxide concentrations while serum carbamazepine concentrations were lower than or the same as baseline levels; (2) all patients were taking drugs that are known to increase serum carbamazepine-epoxide concentrations; (3) status epilepticus failed to respond to intravenous phenytoin loading; (4) seizure exacerbation in all patients was corrected by withholding carbamazepine dose; (5) seizure exacerbation recurred in 1 patient who resumed the same dose of carbamazepine; and (6) there were no prior status epilepticus or daily multiple seizures despite previous toxicities with other antiepileptic drugs in 3 patients. Our experience shows that inconspicuous elevation of carbamazepine-epoxide levels during polytherapy may precipitate a distinct state of drug toxicity characterized by severe exacerbation of seizures. Mental retardation may be a predisposition to this condition. PMID- 8210233 TI - Parceling of mesial frontal motor areas during ideation and movement using functional magnetic resonance imaging at 1.5 tesla. AB - Finger movement-related responses were identified in three discrete sites of mesial frontal cortex in 7 normal subjects using high resolution functional magnetic resonance imaging. During imagination of the same movements there was a differential response with rostral areas more active than caudal areas. Humans have multiple motor areas in mesial frontal cortex that subserve different functions in motor planning and execution. PMID- 8210234 TI - Treatment of Guillain-Barre syndrome with high-dose immune globulins combined with methylprednisolone: a pilot study. The Dutch Guillain-Barre Study Group. AB - In an open study 25 patients with Guillain-Barre syndrome were treated for 5 days with intravenous immune globulins in a dose of 0.4 gm/kg of body weight/day and 0.5 gm of methylprednisolone intravenously per day. The results of this combined treatment were compared with the results from a group of 74 patients who were treated with immune globulins only in a recent Dutch Guillain-Barre trial. In the methylprednisolone-immune globulin treatment group, 19 of 25 patients (76%) improved by one or more functional grades after 4 weeks, as compared with 39 (53%) of 74 patients treated with immune globulin alone (p = 0.04). Also the median time required to the stage of walking independently was reduced in the methylprednisolone-immune globulin treatment group. This pilot study suggests that combined treatment with methylprednisolone and immune globulins in patients with the Guillain-Barre syndrome is more effective than treatment with immune globulins alone; a randomized clinical trial might confirm this. PMID- 8210235 TI - Careers in academic neurology in the decade of the brain. PMID- 8210236 TI - Quality is in the eye of the consumer. PMID- 8210237 TI - Health care reform. PMID- 8210238 TI - Pulmonary thromboendarterectomy. Clinical profile, surgical treatment. PMID- 8210239 TI - Percutaneous transluminal coronary angioplasty. Study of open heart surgical standby; effective patient, OR management. PMID- 8210240 TI - Prostate cancer. Staging through laparoscopic lymphadenectomy. PMID- 8210241 TI - Intraoperative neural monitoring. An introduction for perioperative nurses. AB - Intraoperative neural monitoring is a new science with many potential applications. Anesthesia providers, audiologists, neurophysiologists, and neurologists use intraoperative monitoring to make patient care decisions in the OR. Perioperative nurses' knowledge of anesthesia, anatomy, physiology, surgical procedures, monitoring technology, and electrode application contributes to successful intraoperative monitoring, as does collaboration by the entire surgical team. PMID- 8210242 TI - Cervical intraepithelial neoplasia. Etiology, diagnosis, treatment. PMID- 8210243 TI - Laser education. Are current programs meeting perioperative nurses' needs? AB - As we expected, our surveys found that advanced-level respondents were more highly trained and more experienced, and they perceived themselves as more knowledgeable and more skilled than basic-level laser nurses. Respondents surveyed in 1991 were better educated and more experienced, and they perceived themselves as more knowledgeable and slightly more skilled than those surveyed in 1989. Though these apparent trends are encouraging, other findings indicate that there are large gaps in the knowledge base of even advanced-level laser nurses, particularly in the area of basic laser physics. Of those responding to the item on attendance at educational programs on lasers, 91% had attended some type of laser inservice or education program. Far more respondents, however, had attended manufacturer-provided operational inservice programs or hospital inservice programs on safety compared to those who reported having attended in-depth continuing education courses. In addition, wide discrepancies were observed between the percentages of respondents who had experience with a given type of laser and those who had education beyond the level of operational inservice programs. Apparently, a significant number of nurses who are involved in laser procedures have had no training beyond a very basic level. Respondents rated themselves most knowledgeable about areas related to laser safety and operation. When asked to identify the most important areas of laser education, patient and personnel safety was the paramount concern for all four groups. At the same time, they identified laser physics and tissue interaction as difficult-to-understand, yet important, areas of laser education. PMID- 8210244 TI - Project alpha. One committee studies its progress. PMID- 8210245 TI - How safe are your gloves? A study of protective barrier properties of gloves. PMID- 8210246 TI - Love for life, AORN, perioperative nursing drives the energetic, enthusiastic new President. PMID- 8210247 TI - Are new test methods accurate predictors of gowns' protective barrier effectiveness? PMID- 8210248 TI - Antitrust laws affect nurses. PMID- 8210249 TI - [Experimental evaluation of combination chemotherapy with UFT and cisplatin for lung cancer]. AB - Combined treatment of UFT with cisplatin (CDDP) achieved remarkable elongation of survival time of BDF1 mice, which were intravenously transplanted with Lewis lung carcinoma (LLC). Three cycles of weekly iv administration of CDDP and vindesine (VDS), and daily oral administration of UFT were scheduled. Combination UFT (18 mg/kg/day) with CDDP (6.0 mg/kg/day) yielded tumor-free survivors in all of the treated animals with slight body weight loss. Its efficacy was superior to that of the combination of CDDP with VDS. Supra-additive cytotoxic activity against LLC cells was observed by Isobologram method on the schedule of the exposure to 5 fluorouracil preceding the exposure to CDDP. Additive effect was observed by the reversed schedule of the treatment. Using human non-small-cell lung cancer (NSCLC) cell lines which derived from histologically different type, additive or greater additive sensitivity to both of the sequential treatment schedules with 5 FU and CDDP was observed. These results suggest that the combination chemotherapy of UFT with CDDP for lung cancer may show high antitumor efficacy with low toxicity in a clinical setting. PMID- 8210250 TI - [Early phase II study of MST-16 (sobuzoxane) for breast cancer]. AB - An early phase II study of MST-16 for breast cancer was conducted with the participation of 9 hospitals. MST-16 was administered at three doses; 1) 1,600 mg/body for 5 consecutive days repeating every 4 weeks, 2) 1,200 mg/body for 10 14 consecutive days every 5 weeks, and 3) 1,200 mg/body daily for at least 4 weeks. A total of 28 patients were entered, and 27 cases were eligible. Twenty five cases were evaluated for efficacy and 27 cases for safety. One patient achieved complete response, 2 patients attained partial response, and the response rate thus obtained was 12.0%. Major side effects observed were myelosuppression represented by leukopenia (69.2%) followed by gastrointestinal disorders. These symptoms, however, were reversible by the cessation of administration. PMID- 8210251 TI - [A late phase II study of CPT-11 (irinotecan) in advanced breast cancer. CPT-11 Study Group on Breast Cancer]. AB - A late phase II study of CPT-11 for advanced breast cancer was conducted at 27 institutions. Seventy-nine patients were enrolled, 75 were eligible for the study, and 65 were evaluable for efficacy. One complete response and 14 partial responses were obtained, and the response rate was 23%. The response rate of patients with prior endocrine therapy and prior chemotherapy including adriamycin or other anthracycline drugs was 27% (11/41) and 26% (12/46), respectively. The response rate for patients with estrogen receptor-negative tumors and premenopausal patients was 32% (6/19) and 27% (4/15), respectively. Responses were observed not only for soft tissue lesions such as lymph nodes (5/17), but also for distant metastases in the lungs (8/28) and bone (1/18). The major adverse reactions were myelosuppression and gastrointestinal symptoms. The incidence of Grade 2 or higher leukopenia, anemia, nausea/vomiting, anorexia, diarrhea and alopecia was 68%, 31%, 67%, 59%, 37%, and 30%, respectively. These results suggested that CPT-11 was a promising drug for advanced breast cancer. PMID- 8210252 TI - [The clinical effect of chemotherapy with 5-FU and low-dose CDDP in patients with advanced gastric cancer]. AB - A trial of FP therapy, a novel systemic chemotherapy consisting of 5-FU and low dose CDDP, was carried out in patients with advanced gastric cancer and the clinical effects were evaluated. Five hundred mg/body/day of 5-FU was continuously administered via the central venous catheter for 7 consecutive days and 10mg/day of CDDP was rapidly administered with 500ml saline on days 1-5. The regimen was repeated for at least 4 weeks. The FP therapy was carried out in 22 cases, including several patients who underwent FP as an adjuvant therapy; 1 CR, 2PR's 1MR and 2NC's were obtained among the 6 patients with clinically evaluable lesions, resulting in a response rate of 50%. In four cases, the FP therapy was given as a neoadjuvant therapy, and histopathological examination of the resected specimen revealed histological effects exceeding Grade 2 in all 4 cases. Bone marrow suppression was the most commonly observed side effect, but renal dysfunction and nausea were not found. FP therapy is considered an effective therapy against advanced gastric cancer, from the viewpoint of both the clinical and adverse effects, in comparison with conventional regimen consisting of 5-FU and a single and large dose of CDDP. PMID- 8210253 TI - [Sequential methotrexate/5-fluorouracil therapy with 5'-deoxy-5-fluorouridine against advanced gastric cancer: comparison between bolus injection and drip infusion of 5-fluorouracil administration. Hirosaki Cooperative Study Group for Cancer Chemotherapy]. AB - Forty-two patients with gastric cancer were entered in this study. Forty-one of them were eligible and administered sequential methotrexate (MTX)/5-fluorouracil (5-FU) with 5'-deoxy-5-fluorouridine (5'-DFUR). 5-FU was administered intravenously by drip infusion for 2 hours in 22 cases (group A), and was infused by bolus injection in 19 cases (group B). The treatment schedules were as follows: MTX 100 mg/m2 was given intravenously (i.v.) followed by 5-FU 600 mg/m2 i.v. 2 hours later and leucovorin 15 mg/body i.v. 8 and 20 hours later. This cycle was repeated once a week. 5'-DFUR 1,200 mg/body/day was given orally on 5 consecutive days per week. Three of 20 cases (15%) in group A showed PR, while 5 of 15 cases (33%) in group B showed PR. Median survival time was 2.8 months in group A and 3.7 months in group B. There was, however, no statistical difference. Gastrointestinal toxicity was commonly observed. Leukocytopenia was more severe in group B. Alopecia was more frequently observed in group B (p < 0.025). These results suggested bolus injection of 5-FU was a promising way of administration in sequential MTX/5-FU therapy. PMID- 8210254 TI - [Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. CPT-11 Gastrointestinal Cancer Study Group]. AB - A multi-institutional collaborative late phase II study of irinotecan hydrochloride (CPT-11) was performed on patients with advanced gastric cancer. CPT-11 was administered as a 100 mg/m2 weekly intravenous infusion or as 150 mg/m2 fortnightly. Of 81 registered patients, 77 cases were eligible and 60 cases were evaluable for response. The overall response rate for evaluable cases was 23.3% (14/60), and the response rate was 16.1% (9/45) for the patients who had received prior chemotherapy. The primary tumor showed a 4.5% response, while metastatic lesions in the lymph-nodes, lungs, and liver showed response rates of 36.4%, 33.3%, and 17.4%, respectively. The major toxicities (> or = Grade 3) were leukopenia (41.2%), anemia (28.9%), diarrhea (22.4%) and anorexia (19.7%). These toxicities were generally reversible. CPT-11 showed activity against advanced gastric cancer, suggesting that further clinical studies of CPT-11 combined with other active chemotherapy agents are warranted. PMID- 8210255 TI - [A late phase II study of CPT-11, irinotecan hydrochloride, in patients with advanced pancreatic cancer. CPT-11 Study Group on Gastrointestinal Cancer]. AB - A late phase II study of CPT-11 was conducted to evaluate the antitumor effect and toxicity of CPT-11 in patients with advanced pancreatic cancer as a cooperative study of 19 institutions. From February 1990 to June 1992, 61 patients with advanced pancreatic cancer were enrolled in this study. Fifty-seven patients were evaluable for toxicity and 35 for response. CPT-11 was administered as a 100 mg/m2 weekly intravenous infusion (regimen A) or as a 150 mg/m2 every two weeks (regimen B). The response rate was 11.4% (4/35). The primary tumor showed a 10.3% (3/29) response and the liver metastases showed a 10.5% (2/19) response. The major toxicities were myelosuppression and gastrointestinal symptoms. The incidences (> or = Grade 2) of leukopenia, anemia, anorexia, nausea/vomiting, alopecia and diarrhea were 61.4% (35/57), 56.1% (32/57), 70.2% (40/57), 56.1% (32/57), 40.4% (23/57) and 36.8% (21/57), respectively. The incidence of diarrhea was higher with regimen A than with regimen B, but the antitumor activity was no different between the two regimens. These results suggested that CPT-11 has some antitumor activity against advanced pancreatic cancer. PMID- 8210256 TI - [Late phase II clinical study of irinotecan hydrochloride (CPT-11) in the treatment of malignant lymphoma and acute leukemia. The CPT-11 Research Group for Hematological Malignancies]. AB - A nationwide multi-center cooperative phase II clinical study of irinotecan hydrochloride (CPT-11) was conducted to evaluate its efficacy in intractable malignant lymphoma and acute leukemia. In malignant lymphoma, one course of CPT 11 consisted of intravenous drip infusion at a dose of 40 mg/m2 once daily for 3 consecutive days, performed once a week. In acute leukemia, one course of CPT-11 consisted of intravenous drip infusion at a dose of 15 to 20 mg/m2 a day twice daily for 7 consecutive days (1 cycle), performed every 2 to 4 weeks. Among the 79 patients with malignant lymphoma and 50 patients with acute leukemia enrolled in the study, 66 and 41 patients, respectively, completed treatment. These patients had all undergone chemotherapy prior to treatment. Among the malignant lymphomas, the response rate in non-Hodgkin's lymphoma (NHL), including 9 CRs, was 42% (26/62, 95% CI: 30-54%); of these there was a response rate of 39% (5/13), including 1 CR, in adult T-cell leukemia (ATL) as well. In Hodgkin's disease (HD), on the other hand, there were no cases in which efficacy was demonstrated (0/4). The overall response rate in malignant lymphoma was 39% (26/66), and the response rate even among the recurrent intransigent cases was 42% (16/38). The 50% survival time (MST) in the 74 eligible cases of malignant lymphoma was 153 days. In acute leukemia, on the other hand, partial remission was observed in 2 of 17 cases (12%) of acute lymphocytic leukemia (ALL), but no cases of remission were observed in the 24 patients with acute myelogenous leukemia (AML). The overall remission rate in acute leukemia was 5% (2/41, 95% CI: 1-14%). The principal adverse effects were myelosuppression in malignant lymphoma and gastrointestinal symptoms, including diarrhea, nausea/vomiting, anorexia and abdominal pain, in both malignant lymphoma and acute leukemia, and there was little organ damage to the heart, liver or kidney. Myelosuppression and gastrointestinal adverse effects were severe in some of the patients, so caution is required. Based on the above findings, CPT-11 appears to be efficacious in the treatment of non-Hodgkin's lymphoma. PMID- 8210257 TI - Risk status for dropping out of developmental followup for very low birth weight infants. AB - Not keeping scheduled visits for medical care is a major health care issue. Little research has addressed how the interaction of demographic and biomedical parameters with psychosocial processes has an impact on appointment keeping. Typical factors are stress of daily living, methods of coping, social support, and instrumental support (that is, tangible assistance). In this study, the authors examine the role of these parameters and processes in the risk status for dropping out of a developmental followup program for very low birth weight infants. The findings suggest that the stress of daily living is a significant predictor for the mother's return when the infant is 6 months of age (corrected for prematurity). The predictors for return at 24 months corrected age include marital status, race, gestational age of the infant, maternal intelligence, and efficacy expectations. Providing transportation was found to be a successful intervention strategy for a subgroup at very high risk for dropping out due to a constellation of biomedical, demographic, and psychosocial factors. PMID- 8210258 TI - A diabetes control program in a public health care setting. AB - The Houston Diabetes Control Program is part of an effort by the State of Texas and approximately 30 other programs throughout the United States to ensure that persons with diabetes-related complications receive ongoing state-of-the-art preventive care and treatment. For the past 5 years, this program has served an urban, high-risk patient population with special cultural, ethnic, and economic challenges. The intervention has included the development and implementation of protocols for the prevention and care of diabetes-related complications of the eyes, lower extremities, and cardiovascular system, as well as general management of diabetes and patient and professional education. The program is ongoing in nine community health centers located in low-income neighborhoods of a large metropolitan area. The results thus far indicate an increase in sensitive eye examinations from 8 percent to 26 percent of the patient population, a reduction in incidence of legal blindness from 9.5 to 2.7 per 1,000 during a 4-year period, an increase in foot examinations from 18 percent to 44 percent of the patient population, and 77 percent of hypertensive patients in good control of blood pressure at less than 160 over 95 mmHg (millimeters of mercury). On the average, there have not been significant long-term improvements in weight reduction or blood glucose control. The major challenges for this program are (a) improvement in control of glycemia, hypertension, and cholesterol; (b) more effective diet and physical activity interventions; and (c) more effective education approaches that help patients to understand metabolic and cardiovascular functions. These challenges will require collaboration of health care professionals in constructive and imaginative ways through their unselfish commitment toward common goals. PMID- 8210259 TI - Integrating behavior and intention regarding mammography by respondents in the 1990 National Health Interview Survey of Health Promotion and Disease Prevention. AB - Achieving and maintaining high rates of screening mammography are major public health priorities. This report examines data from the 1990 National Health Interview Survey of Health Promotion and Disease Prevention on the utilization of mammography among women ages 40-75. Results show that progress is being made in some areas--57.7 percent of women "ever had" a mammogram; 50.3 percent, in previous 2 years. However, those not having repeated regular screening appear to be a sizable proportion. Only 28.6 percent of women ages 40-75 had been both screened on the recommended age-specific schedule and expressed an intention to continue screening; another 29.2 percent indicated no intention to have a mammogram in the near future. Income, clinical breast examination, and Pap (Papanicolaou's) test, having no regular source of care, region of the country and residential variables, smoking status, not exercising, not knowing how to do breast self-examination, and race were among the variables having the strongest associations with mammography status. Several groups in the population therefore remain at risk of not receiving regular screening. The combination of mammography status to date and future intention to have the examination provides an important perspective on efforts to reach public health screening objectives and appears to provide a strategy for targeting interventions. PMID- 8210260 TI - Characteristics and causes of penetrating eye injuries reported to the National Eye Trauma System Registry, 1985-91. AB - Ocular trauma is one of the most important preventable causes of visual impairment. The National Eye Trauma System was developed to provide optimal clinical care for severe ocular injuries, to foster research on eye injury, and to increase awareness of ocular trauma as a public health problem. From 1985 through 1991, the National Eye Trauma System Registry collected data on 2,939 cases of penetrating eye injury reported by ophthalmologists at 48 collaborating eye trauma centers in 28 States and Washington, DC. Eighty-three percent of the cases involved men; the median age of the patients was 27 years, ranging from 1 to 92 years of age. Seventy-seven percent of the injuries were unintentional, 22 percent were the result of assault, and 1 percent were self-inflicted. In 62 percent of the cases studied, the injured person's initial best corrected visual acuity in the injured eye was the ability to perceive hand motion, or worse. The settings in which the injuries occurred included the home (28 percent), the worksite (21 percent), at recreation (11 percent), and in transportation (8 percent). At the time of the injury, 1.5 percent of the injured persons were wearing safety glasses and 2.9 percent were wearing nonsafety glasses. There was evidence of definite or possible alcohol use by at least 24 percent of the injured persons and illicit drug use by 8 percent. The most frequent types of tissue damage included corneal or scleral laceration, traumatic cataract, intraocular foreign body, vitreous hemorrhage, and prolapse of intraocular tissue. Analyses of the causes and characteristics of ocular injuries reported to the National Eye Trauma System Registry will help identify high risk settings for such injuries. Results will be used to develop and implement interventions that will reduce the incidence of eye trauma. PMID- 8210261 TI - Assessment of E-coding practices and costs in Massachusetts hospitals. AB - Hospital discharge data are a potentially useful information resource for documenting the epidemiology of nonfatal injuries. However, hospitals often do not include E-codes that identify external causes of injury in discharge abstracts. One barrier has been assumed to be the cost of assigning E-codes to medical records. Directors of medical records at hospitals in Massachusetts were surveyed to assess the validity of a cost-assessment study by Rivara and coworkers and to determine what resources they would need to E-code all injury discharges. According to Rivara's estimates, injury coding an additional 500 hospital discharges would entail a continuing cost to each hospital of about $600 a year. More than half of the survey's 101 respondents believed that the estimates were accurate, 16 percent believed that the estimates were inaccurate, and 27 percent were unable to assess the potential costs. Among the resources needed to E-code all injury-related discharges, respondents most often cited training for those who assign the codes and the approval of the hospital administration. Only 20 percent of the respondents cited needs directly related to ongoing costs. The perception by hospitals of the cost of E-coding, frequently cited as a major barrier to the use of hospital discharge data as an injury surveillance source, did not emerge in this survey as an overriding concern. PMID- 8210262 TI - Knowledge, intent to use, and use of smokeless tobacco among sixth grade schoolchildren in six selected U.S. sites. AB - Questionnaires on smokeless tobacco use were completed by 781 sixth grade students in 15 schools at six locations in the United States. The students were both American Indian-Alaska Native and non-American Indian-Alaska Native. The Indian and Alaska Native schoolchildren were experimenting with and regularly using smokeless tobacco at higher rates that non-Indian schoolchildren. At Indian Health Service sites, 28.1 percent of the children reported current use of smokeless tobacco, compared with 3.3 percent of the children elsewhere. For girls reporting smokeless tobacco experimentation, the comparison was 68.9 percent at Indian Health Service sites and 8.7 percent at non-Indian sites; for boys, it was 79.1 percent from the Indian sites and 35.4 percent from the non-Indian sites. For those students who had tried smokeless tobacco, more than half also reported having tried cigarettes. The majority of all sixth grade students surveyed were aware of the health risks of smokeless tobacco use in that it is an increased risk for cancer. Additional research is needed to determine appropriate interventions. PMID- 8210263 TI - Public health department tracking of high-risk drug users. AB - The Multnomah County (OR) Health Department received a National Institute on Drug Abuse grant to develop effective interventions and education to reduce the spread among injecting drug users of the human immunodeficiency virus that causes AIDS. One year into the project, new approaches were developed to locate the drug users for followup interviews. County data bases were accessed and arrangements were made to conduct interviews in jails and prisons. Similar techniques were employed to locate tuberculosis patients with positive results. PMID- 8210264 TI - Self-reported illness among travelers to the Russian Far East. AB - This study evaluated the risk of travelers to the Russian Far East developing acute gastrointestinal or respiratory symptoms. Passengers and crew on 10 commercial airline flights from the Russian Far East to the United States were asked to complete a health questionnaire that asked age, sex, country of residence, length of stay, foods and beverages consumed, and about gastrointestinal or "flu" symptoms. Questionnaires were returned by 353 of 662 persons (53.3 percent). The most frequently reported symptoms were diarrhea (N = 18; 5.1 percent) and "flu" symptoms (N = 15; 4.2 percent). Among those people who reported symptoms, most were sick for 3 days or less, although 10 (27.0 percent) were still sick at the time that they entered the United States. Age and sex were not associated with symptoms. Persons who drank untreated tap water were more likely to have gastrointestinal symptoms (relative risk = 2.7; 95 percent confidence interval = 1.2, 5.9) while those who drank bottled or canned fruit juice were protected (relative risk = 0.4; 95 percent confidence interval = 0.2, 0.8). The incidence of "flu" symptoms was similar to the rate for the general population of the United States while the incidence of gastrointestinal symptoms was increased and only slightly less than the rate among travelers to developing countries. Travelers may wish to restrict consumption of untreated tap water and increase consumption of fruit juices. Additional work is needed to identify the pathogens responsible for acute illness among travelers to the Russian Far East. PMID- 8210265 TI - New Surgeon General's AIDS report provides updated information. PMID- 8210266 TI - Measuring the health behavior of adolescents: The Youth Risk Behavior Surveillance System and recent reports on high-risk adolescents. PMID- 8210267 TI - Measuring adolescent behaviors related to unintentional injuries. PMID- 8210268 TI - Measuring adolescent behaviors related to intentional injuries. PMID- 8210269 TI - Overview of the Youth Risk Behavior Surveillance System. PMID- 8210270 TI - Measuring tobacco use among adolescents. PMID- 8210271 TI - Measuring use of alcohol and other drugs among adolescents. PMID- 8210272 TI - Measuring adolescent sexual behaviors and related health outcomes. PMID- 8210273 TI - Measuring dietary behaviors among adolescents. PMID- 8210274 TI - Measuring physical activity among adolescents. PMID- 8210275 TI - Results from the national school-based 1991 Youth Risk Behavior Survey and progress toward achieving related health objectives for the nation. PMID- 8210276 TI - Designing health promotion approaches to high-risk adolescents through formative research with youth and parents. AB - Young people who engage in multiple health risk behaviors such as alcohol and other drug use, unprotected sexual activity, smoking, and violence, are a serious public health concern. To help identify potential strategies for influencing these behaviors, focus groups were conducted with 160 youth ages 10-18 years. For additional insights, focus groups also were held subsequently with 70 parents and grandparents of youth of similar ages. The youth participants were well-informed about most of the risky behaviors and their health consequences. Safe sex practices and the prevention of human immunodeficiency virus (HIV) infection were the exceptions. Despite this understanding, participants spoke of engaging in these behaviors as part of a lifestyle common to the high-risk environments where they live. The youth said that knowing why these practices were harmful was not enough to help them change the behavior. The need for skills building and support systems to reinforce their generally high level of awareness was evident. Love, home, family, and safety were cited as very important. Many participants said they wanted to talk to someone they could trust, who knew what they were going through. The groups of parents and grandparents were concerned about the physical dangers facing their adolescents and about peer influence. They also acknowledged their own mixed messages to their youth. The focus group findings suggest that health promotion strategies for high-risk youth should be comprehensive rather than categorical, with nonjudgmental, interpersonal communication integrated into community-based programs. To be relevant, program strategies must reach outside the usual channels and incorporate the high-risk environment where these youth live. PMID- 8210277 TI - Stereotype or reality: another look at alcohol and drug use among African American children. AB - The Center for Substance Abuse Prevention's Division of Communications Programs launched its Urban Youth Public Education Campaign in late 1990 to target African American youth in 14 cities with prevention messages about alcohol and other drugs. During the market research phase of the campaign, the Center sought to determine the extent inner city African American children are impacted by alcohol and other drugs and how widespread the use of these substances is among younger children. Is it rampant and universal, as some press accounts have it, or are the images portrayed by the news media, by popular movies, and by other communication outlets fueling harmful stereotypes? The campaign's market research consisted of in-depth reviews of the literature, of personal communications, conference proceedings, grant and contract reports, monographs, newspaper and magazine articles, and of national survey results, and the analysis of findings from focus groups conducted with 143 African American children living in several urban environments. Although information and conclusions gleaned from the market research revealed a longstanding trend of comparatively lower rates of alcohol and drug use by African American youth, also disclosed was a need for an expanded framework to address the problems of substance abuse within the African American community. An expanded framework acknowledges the dimension of substance use and abuse but also addresses three other dimensions--involvement, exposure, and victimization--that unfold as having major significance for this population of youth who live in urban, high-risk environments. PMID- 8210278 TI - Crafting effective tobacco counteradvertisements: lessons from a failed campaign directed at teenagers. AB - Focus group research conducted by the Centers for Disease Control and Prevention's Office on Smoking and Health suggested that the desire of teenagers to gain control over their lives would make them responsive to a counteradvertising strategy aimed at exposing the predatory marketing techniques of the tobacco industry. On the basis of this strategy, the office developed draft print advertisements and a rough TV commercial featuring such theme lines as "You get an image. They get an addict." In those ads, "they" referred to cigarette companies. Subsequent testing of the campaign materials, however, indicated that the subtle, sophisticated execution of this concept of manipulation by the industry did not communicate clearly and effectively to an audience of young teens. In fact, 38 percent of those who viewed the rough TV spot believed that the main message promoted smoking. These negative test findings underscore the critical need for ongoing audience research throughout the creative process to ensure that campaign planners stay "in tune" with their consumers. PMID- 8210279 TI - Longitudinal study of delinquency, drug use, sexual activity, and pregnancy among children and youth in three cities. AB - Using data from a collaborative program of research, this paper examines the prevalence of delinquency, alcohol and drug use, sexual intercourse, and pregnancy among youth in three urban settings. The findings indicate that a substantial portion of adolescents are involved in these behaviors. There are indications that for many youth the initiation of delinquency and drug use is occurring before the teenage years. There are also indications that all of these behaviors are often co-occurring, suggesting that comprehensive intervention programs may be required. Importantly, the high rate of sexual activity and pregnancy, combined with alcohol and drug use, suggests that greater attention to this combination of behaviors is needed. PMID- 8210280 TI - [Multiple sphincterotomies in the surgical treatment of cataracts in narrow pupils]. AB - Deficient mydriasis of diverse etiology renders extracapsular cataract extraction and posterior chamber intraocular lens implantation technically difficult. Several techniques are available to improve surgical results when this problem is present. We have used multiple sphincterotomies in 6 patients with narrow pupils undergoing cataract extraction. We discuss the indications, intraoperative complications and postoperatory evolution of these cases. PMID- 8210281 TI - Argon laser photocoagulation for chronic clinically significant cystoid macular edema. AB - We report the therapeutic outcome of 14 eyes of 11 patients with chronic clinically significant pseudophakic cystoid macular edema refractory to medical management who underwent argon laser photocoagulation of the perifoveal area. Inclusion criteria included chronic cystoid macular edema of more than six months duration of decreased visual acuity (20/100 or less), positive fluorescein angiogram and contact lens examination, pseudophakos with posterior chamber intraocular lens and intact posterior capsule, normal fasting blood sugar, failed medical treatment and minimal follow up of six months. Fifty per cent of the eyes improved after laser treatment (p = .0345, relative to unchanged plus worsened cases). Further prospective, randomized, clinical trials are recommended to define the effectiveness of this treatment protocol. PMID- 8210282 TI - Cations, oxidants, light as causative agents in senile cataracts. AB - Lens transparency is a function of regular cell shape, regular cell volume, minimal extracellular space, and minimal scatter elements. The cellular structure and molecular structure of the lens is reviewed. The importance of the cytoarchitecture especially the sutures, is discussed. The high cholesterol: phospholipid ratio of the lens fiber cell membranes is related to the functions of low permeability, low fluidity, and mechanical stability. Also reviewed are the contributions of the lens crystallins to lens clarity and to lens refractive index. The importance of intracellular and extracellular cation and water concentrations are reviewed. Finally the effects of systemic diseases, oxidation, and light on lens clarity are discussed relative to changes in lens fiber cell cation concentrations. PMID- 8210283 TI - Antibodies to lens crystallins after endocapsular cataract surgery. AB - Levels of serum antibodies against lens alpha, beta H and beta L crystallins were determined in 15 patients before and after endocapsular cataract extraction. The most abundant antibody at the time of surgery was anti-beta L, followed by anti beta H and anti-alpha. An increase in the basal levels of these antibodies was seen after surgery in 93 percent of the cases. Relative increase was highest for anti-alpha, followed by anti-beta H and anti-beta L. There were individual variations both in the shape of the time-dependent antibody response after surgery and in the relative intensity of the response to the different antigens. The endocapsular technique therefore leads to the release of crystallins into the anterior chamber in sufficient amounts to provoke in many patients a humoral immune response. PMID- 8210284 TI - Melanins and lens pigments: a comparative study. AB - Based on previous findings that lens pigments and melanins share many physicochemical properties, human lens pigments and natural (hair) and synthetic melanins were submitted to oxidation with permanganate under strong acidic conditions. This procedure has been utilized for the characterization of melanins and results in the well defined products, thiazole-4,5-dicarboxylic acid (TDCA) and pyrrole-2,3,5-tricarboxylic acid (PTCA), which can be quantitated by high performance liquid chromatography (HPLC). PTCA is regarded as a marker of black eumelanins and was therefore a main component of synthetic DOPA-eumelanin and dark hair. Its identity was established by synthesis from 5-hydroxyindole-2 carboxylic acid. TDCA derives from pheomelanins and was therefore an important component of red hair and synthetic GSH-pheomelanin. TDCA was identified by its retention time relative to PTCA. The analysis of a series of cataract digests of increasing pigmentation (type I < type IV < type V) and a purified fraction of lens pigments (DE52 pigment) revealed the presence in these preparations of both PTCA and TDCA. The concentration of TDCA significantly increased with the degree of pigmentation of the digests and reached a maximum in the DE52 pigment. The TDCA/PTCA ratio was high in the lens preparations and comparable to that given by hair pheomelanin. These findings support that pheomelanin is an integral part of lens pigments. By comparing the yields of TDCA in GSH-pheomelanin and in the purified lens pigment, a 9% contribution of pheomelanin to the lens pigment was estimated. PMID- 8210285 TI - Displaced amacrine cells in the ganglion cell layer of the ground squirrel retina. AB - In some mammals a large portion of the retinal neurons of the ganglion cell layer are not ganglion cells. These neurons, lacking axons which pass to the brain via the optic nerve, are termed displaced amacrine cells. The present study assessed the number of displaced amacrine cells in the thirteen-lined ground squirrel (Spermophilus tridecemlineatus). We compared the number of labeled cells in the ganglion cell layer after HRP injection of optic tracts and target nuclei with the total number of neurons in the ganglion cell layer. We conclude that approximately one half of the neurons in the ganglion cell layer are displaced amacrine cells, the other one half are ganglion cells. The displaced amacrine cells are on the average smaller than the ganglion cells. Our results provide a rationale for renewed study of relation of ganglion cell morphology and physiological functional type in this species. PMID- 8210286 TI - [Possible origins of the gene of Hermansky-Pudlak in Puerto Rico]. AB - Five out of six albino persons in Puerto Rico suffer from the Hermansky-Pudlak syndrome. This syndrome has been reported also in other countries such as Great Britain, the Netherlands, Belgium, and Mexico, among others. Due to the geographical isolation of the island it is likely that these patients share a common ancestor. In explaining how the gene may have arrived to Puerto Rico the following possibilities are considered: (1) British soldiers attacking the island since 1595. (2) Dutch attackers in 1625. (3) aboriginal tribes. (4) slave traders. PMID- 8210287 TI - [Continuing education in ophthalmology]. PMID- 8210288 TI - [Integrated model for the prevention of blindness based on the Peruvian Organization for the Campaign against Blindness (OPELUCE)]. AB - Numerous strategies and policies have been designed for the prevention of blindness. Their implementation, however, may find considerable operational difficulties in the developing countries. Following WHO (World Health Organization) recommendations, the Peruvian organization against blindness (OPELUCE) has designed an Integral Model for the Prevention of Blindness in Peru. This model includes the training of health personnel and educators, informing the community on ocular preventive aspects, medical and surgical treatment of patients and training programs for the blind. The model has been modified for its application in urban, and urban-marginal areas as specific programs for the prevention of blindness due to glaucoma, diabetes, and accidents, and for the detection of visual problems at the school level. PMID- 8210289 TI - [Phako-small port]. AB - The smallport system is a new technology that brings to surgeons who begin in phacoemulsification more advantages and control in surgery, more security and less time required for learning. The authors show the differences (advantages and disadvantages) between standard systems and the endocapsular "smallport". In nuclei up to grade 3 hardness we have good results with low phaco power (5-10%) and higher linear aspiration (200 mmHg) causing minimal loss of endothelial cells and quick visual rehabilitation. PMID- 8210290 TI - [Alzheimer's disease: the untold story]. AB - Alzheimer's Disease. The untold story. After considering the potential relationship between amyloid deposits and myxedematous infiltrations, the hypothesis is formulated that Alzheimer's disease may be due to functional hypothyroidism and may thus respond to thyroid therapy. PMID- 8210291 TI - Visual function after surgery for early cataract. AB - Glare disability and contrast sensitivity loss can be present in cataract patients with minimally reduced visual acuity. Objective and subjective visual function was analyzed in 72 patients (mean visual acuity = 20/40) before and after cataract surgery. Following surgery, most subjects regained normal function in all tests. Improvement in contrast sensitivity and reduction of glare disability were independent of preoperative visual acuity. Subjective improvement in visual function was predicted by acuity and contrast sensitivity tests. PMID- 8210292 TI - [Iridectomy, an alternative in the treatment of total hyphema]. AB - Iridectomy as a therapeutic alternative for total hyphema. Complete resorption of blood in eyes with posttraumatic total hyphema and high intraocular pressure not amenable to medical therapy was accomplished by means of peripheral iridectomy. No postoperative complications were noted in any of the six patients studied and intraocular pressure remained normal without medications for at least one year after the surgical procedure. Pupillary block and obstruction of the drainage pathway by the clot could account for the secondary glaucoma in these patients. PMID- 8210293 TI - Surgically induced astigmatism. A comparison of different cataract incisions and closures. AB - A single center, single surgeon, nonrandomized, prospective clinical trial was performed comparing the keratometric induced astigmatism by different types of incisions and closures, one day, one week, one month and three months after 255 cataract surgeries. After phacoemulsification, or in rare cases after extracapsular cataract extraction, through a scleral pocket or limbal incision, patients received either a 5 x 6 mm, 5.5 mm, or 6 mm diameter polymethylmethacrylate optic posterior chamber intraocular lens. Incision was closed with either none, one horizontal or radial, or running 10-0 nylon suture. Vector analysis calculations of prism diopters of mean postoperative-induced keratometric astigmatism showed a trend to lesser values at each interval in scleral pocket incisions but statistically significant difference only at 1 day and 1 week between 9-mm and 6-mm limbal, and 5-mm and 6-mm scleral pocket incisions. Other subgroup analyses, including incision shape and distance from limbus, and type of suture, did not reach statistical significance. Horizontal, 5 mm, sutureless scleral tunnel incision showed less induced astigmatism with more rapid stable refraction. PMID- 8210294 TI - Acute liver failure: improving outcome despite a paucity of treatment options. PMID- 8210295 TI - Complex genetics of type 2 diabetes: thrifty genes and previously neutral polymorphisms. AB - Type 2 diabetes is likely to be a polygenic disease, with a combination of major and minor genes affecting obesity, insulin secretion, and insulin action. Amongst these inputs, the 'thrifty genotype' hypothesis is most likely to apply to the predisposition to develop obesity, since the ability to store scarce fuels in periods of starvation could lead to obesity given a western lifestyle. Other genetic variations that were neutral with respect to food deprivation could be harmful with food excess. These could include 'defects' in islet cell function: examples could be mutations in the glucokinase gene and the genetic factors leading to amyloid deposition. The occurrence of associated lipid abnormalities or hypertension is probably due to additional specific genetic determinants that also become exaggerated by a modern lifestyle. The interactions between different genetic and environmental inputs are complex, and will probably be elucidated piecemeal as different genetic determinants are identified. PMID- 8210296 TI - The risks of symptomatic vaginal candidiasis after oral antibiotic therapy. AB - It is generally accepted that antibiotic use can result in vaginal fungal overgrowth, although evidence estimating the extent to which this causes symptomatic vaginitis is scant. In a study using the prescription of vaginal antifungal preparations as a surrogate measure of vaginal candidiasis, a cohort of women taking antibiotics had a higher incidence of vaginal candidiasis after antibiotic exposure than beforehand (relative risk 2.3; 95% confidence interval 1.9-3.0); this risk was highest in those aged 36-40 years (RR 6.0, 95% CI 2.9 12.5). The attributable risk was highest among those who were taking cephalosporins (AR 12.8%, 95% CI 9.1-16.5). In a case-control study, comparing previous antibiotic exposure among women using vaginal antifungal agents and matched controls, antibiotic exposure was higher among those using vaginal antifungal agents during the previous 28 days, with an odds ratio of 5.5 (95% CI 3.8-7.9). PMID- 8210297 TI - Trends in the prevalence of asthma and dyspnoea in first year university students, 1972-89. AB - The prevalence of asthma and dyspnoeic symptoms were studied in undergraduates from Ireland, north and south, entering Queen's University Belfast in the years 1972, 1978, 1983, 1986 and 1989. The records of students' compulsory entry medical examination, including responses to questions on dyspnoeic symptoms in a health screening questionnaire, were reviewed. Between 1972 and 1989, the 12 month period prevalence of asthma increased from 1.3% to 2.84% (p < 0.001). This increase was not accounted for by the changes in the sex, or socioeconomic structure of the student body. In non-asthmatics the prevalence of dyspnoea rose from 5.49% to 8.30% (p < 0.01). In students with diagnosed asthma, the proportion with dyspnoeic symptoms did not significantly increase (p = 0.167). There was a greater than two-fold increase in the prevalence of diagnosed asthma in this population between 1972 and 1989. The prevalence of asthma was higher in rural than in urban students. There was also an increased reporting of dyspnoea in non asthmatics, the significance of which is unclear. PMID- 8210299 TI - Mitochondrial DNA transfer RNA mutation Leu(UUR)A-->G 3260: a second family with myopathy and cardiomyopathy. AB - A family with maternally inherited myopathy and cardiomyopathy is described. Mitochondrial DNA analysis showed a heteroplasmic point mutation at position 3260 in the leucine transfer RNA gene, previously reported in a large Italian family with a similar phenotype. This observation confirms pathogenicity of this mutation and suggests phenotypic specificity. PMID- 8210298 TI - Rhabdomyolysis and acute renal failure in unsuspected malignant hyperpyrexia. AB - Malignant hyperpyrexia is an inherited disorder of skeletal muscle characterized by intermittent hypermetabolic crises, usually triggered by anaesthetic agents. We present the case of a 19-year-old man who developed acute renal failure following an apparently uneventful general anaesthetic for appendicectomy. His renal failure was found to be secondary to rhabdomyolysis, and he made a full recovery after requiring haemodialysis for 14 days. Both the patient and his father were later discovered to have an underlying metabolic susceptibility to malignant hyperpyrexia. We propose that an undetected hypermetabolic crisis precipitated rhabdomyolysis and subsequent acute renal failure in this patient. PMID- 8210300 TI - Hyperglycaemia and mortality from acute stroke. AB - Hyperglycaemia has been observed after acute stroke, and is associated with a poor prognosis. It is not known whether this is due to the stress response of the acute illness or whether hyperglycaemia is, in itself, harmful to ischaemic nervous tissue. Seventy-one patients admitted to hospital with acute stroke and no history of diabetes or other acute illness were recruited, and fasting blood sampling was carried out within 24 h of symptom onset, for plasma glucose and stress hormones and levels of haemoglobin A1c (HbA1c). Computerized tomography of the brain was carried out on 77% of the subjects. The subjects were followed up for 3 months or until death. Glucose levels were higher in subjects who died during the course of the study (p = 0.025), but this relationship became non significant after age (p < 0.001) and cortisol (p = 0.001) levels were taken into account with multivariate analysis. The correlation between serum cortisol and the volume of the lesion on CT scan was also stronger than the relation of glucose with volume. Haemoglobin A1c had no relationship with either mortality or lesion volume. These findings suggest that the hyperglycaemia seen after an acute stroke is secondary to a stress response and they do not support the theory of hyperglycaemia being harmful to ischaemic nervous tissue. These findings have implications for the treatment of acute stroke with hypoglycaemic agents. PMID- 8210301 TI - The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. AB - The British Isles Lupus Assessment Group (BILAG) index is a computerized index for measuring clinical disease activity in systemic lupus erythematosus (SLE), which was developed according to the principle of the physician's 'intention to treat'. The index allocates separate alphabetic scores to each of eight organ based systems; a total score is not calculated. This study demonstrated good between-rater reliability for the BILAG index for each organ-based system. There was no evidence of bias between observers. The BILAG index had good overall sensitivity (87%) and specificity (99%) when compared with the 'gold standard' criterion (starting or increasing disease-modifying therapy). There were high positive predictive values overall (80%), and for each organ-based system, with the exception of the neurological system. PMID- 8210302 TI - Genetic linkage analysis, clinical features and prognosis of autosomal dominant polycystic kidney disease in Northern Ireland. AB - Fifteen families with autosomal dominant polycystic kidney disease were analysed for coinheritance of the disease and DNA markers flanking the PKD1 locus. Eleven families demonstrated linkage to PKD1 markers. Two families were unlinked to the PKD1 locus (non-PKD1) and in two families the markers were uninformative. The clinical features and prognosis of 49 subjects with a PKD1 genotype were compared with 17 non-PKD1 subjects. The age at diagnosis in non-PKD1 subjects (37 +/- 11 years) was significantly later than PKD1 subjects (25 +/- 13 years, p < 0.001). Only two (12%) non-PKD1 subjects presented initially with clinical features of autosomal polycystic kidney disease compared to 27 (55%) of PKD1 subjects (p < 0.002). Hypertension was more common in PKD1 compared to non-PKD1 subjects (29% vs. 12%), as was stage renal failure (25% vs. 6%). Seventy-five percent of non PKD1 subjects had not developed end-stage renal failure by the age of 54 years compared to only 35% of PKD1 subjects. Most families with autosomal polycystic kidney disease in this population have disease due to mutations at the PKD1 locus. However, the proportion of non-PKD1 families appears to be higher than estimates for other populations. This study also confirms initial reports that subjects with a non-PKD1 genotype have a milder disease with a better prognosis than those with a PKD1 genotype. PMID- 8210303 TI - Fetal growth and auto-immune thyroid disease. PMID- 8210304 TI - Management of paroxysmal atrial fibrillation. AB - Paroxysmal atrial fibrillation is a common, poorly understood and difficult-to treat arrhythmia. Although it tends to be treated in a similar fashion to chronic atrial fibrillation, its pathophysiology is different, and drugs commonly used for chronic atrial fibrillation may have only limited value in treating paroxysmal atrial fibrillation. A broad range of presenting clinical symptoms may be associated with this arrhythmia, and even in the asymptomatic patient, there may be a risk of serious thromboembolic events. In symptomatic patients, effective control of paroxysms with antiarrhythmic therapy can often be difficult, and the role of anticoagulation remains controversial. This review attempts to clarify these issues, by surveying the range of therapies available. PMID- 8210305 TI - Causes of hospital-acquired septicaemia--a case control study. AB - Hospital-acquired septicaemia is common and an important cause of morbidity and expense. Few studies have explored its cause by comparing features of people who do and do not develop septicaemia--the aim of this study. All blood cultures were monitored over one year in a 400-bed tertiary care hospital where special care is taken with intravenous cannulae to prevent septicaemia. Cases had at least one positive blood culture taken at least 48 h after admission. The nearest two patients in the same ward were controls, and information was abstracted on all three from the hospital records by a research nurse. There were 84 cases during the 12 months (3.8 per 1000 admissions) and 167 controls. Univariate odds ratios (95% CI) were 5.57 (2.06-15.95) with the presence of a central venous line, 3.40 (1.16-16.40) with total parenteral nutrition, 2.41 (1.30-4.32) with blood transfusion, 2.10 (1.16-4.56) with immunosuppressive disease, 2.06 (1.02-4.44) with the presence of a urinary catheter and 0.32 (0.17-0.69) with recent surgery. Conditional logistic regression identified a central venous line and blood transfusion to be independent risk factors for septicaemia, odds ratios (and 95% CI) being 5.14 (1.74-15.23) and 2.74 (1.28-5.88), respectively, while recent surgery and antibiotic prophylaxis were independently 'protective' at 0.31 (0.12 0.79) and 0.38 (0.16-0.90), respectively. Thus, in a hospital where great care has been taken to avoid septicaemia, especially by attention to intravenous cannulae, there were only two independent risk factors for the development of hospital-acquired septicaemia--a central venous line and blood transfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210306 TI - Accelerated hypertension--patterns of mortality and clinical factors affecting outcome in treated patients. AB - We evaluated the outcome of patients presenting with accelerated hypertension, as part of an audit of the Aberdeen Hypertension Clinic database. Of 3928 patients (2005 male, 1923 female) referred for assessment of hypertension, 128 (77 male, 51 female) presented with accelerated hypertension. The main outcome measures were systolic and diastolic pressure, length of time from referral to death or censor date, and cause of death. Accelerated hypertensives had a higher death rate than other hypertensives. Using life-table analysis, age and serum creatinine at referral were sufficient to predict survival. Almost 50% (15/31) of the deceased accelerated hypertensives died of acute myocardial infarction. Mean survival after referral was estimated as 18 years for accelerated hypertensives (mean referral age 52 years) and 21 years for other hypertensives (mean referral age 48 years). Blood pressure fell most during the first year of treatment, and declined steadily thereafter. Systolic blood pressure fell by a mean of 50 mmHg and diastolic pressure by 30 mmHg in the first year, and at about 2 (diastolic) and 1 (systolic) mmHg/year for the next 10 years. Thus although the prognosis for accelerated hypertensives is not quite as good as for other hypertensives, with suitable care they can survive for a considerable period. PMID- 8210307 TI - Radioiodine therapy for hyperthyroidism in young patients--perception of risk and use. AB - Although radioiodine is increasingly the treatment of choice in hyperthyroidism, there are regional differences in its use which reflect, in part, concerns regarding safety. We investigated attitudes amongst general practitioners and consultant physicians to the role of radioiodine therapy, and reviewed our own radioiodine prescribing in patients aged less than 40 to elucidate any influence of age and/or sex. We surveyed general practitioners in the former Central Birmingham Health District and consultant physicians in the West Midlands Region to investigate treatment preferences in hyperthyroidism and perceived risk from radioiodine of hypothyroidism, carcinogenesis and infertility. Of 230 general practitioner and 130 consultant physician respondents, less than 1% considered radioiodine the treatment of choice in a 25-year-old female presenting with hyperthyroidism. At relapse after antithyroid drug treatment in a 25-year-old female, only 16.5% of general practitioners and 23.9% of physicians advocated radioiodine, the greatest number preferring partial thyroidectomy. For a 65-year old at presentation, 49.1% of general practitioners and 62.3% of physicians considered radioiodine the treatment of choice. More than 10% failed to note the risk of hypothyroidism following radioiodine, while 11-34% perceived increased risk of malignancy or infertility. Review of our own practice demonstrated that of 100 patients given radioiodine, 94% were cured of hyperthyroidism when reviewed at a mean of 2.4 years from latest treatment, 70% being hypothyroid. Females given radioiodine were treated less promptly following diagnosis of hyperthyroidism than males (2.2 +/- 0.26 years vs. 1.6 +/- 0.4) and were more likely to have received a preceding course of antithyroid drugs (78% vs. 57%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210308 TI - Transoesophageal versus transchest DC cardioversion. AB - Attempted cardioversion via the oesophagus (transoesophageal cardioversion) was compared with the transchest approach (transchest cardioversion) in a randomized trial of 100 consecutive patients with atrial fibrillation. For the transoesophageal group, 30, 50 and 100 J were delivered via an oesophageal electrode with subsequent 200 and 360 J transchest if required. For the transchest group, 50, 100, 200 and 360 J were delivered if required. In the transoesophageal group, 36/50 (72%) of patients cardioverted using the transoesophageal route alone, and in the transchest group, 41/50 (82%) of patients cardioverted (p = NS). First shock success was similar for the transoesophageal and transchest groups: 13/50 (26%) vs. 8/50 (16%) respectively. The mean number of shocks required to achieve successful cardioversion was identical for the transoesophageal and transchest groups (2.6). However, transoesophageal cardioversion was more successful than transchest cardioversion at energies < or = 100 J (36/50 [72%], and 17/50 [34%], p < 0.05). Median total energy for successful cardioversion was lower for patients in the transoesophageal group (180 J) than the transchest group (350 J) and mean peak current at successful cardioversion was also lower for patients in the transoesophageal group (21.7 A) than the transchest group (27.3 A) (p < 0.05). No oesophageal complications occurred. Thus, using an oesophageal electrode, cardioversion can be achieved as successfully as using the transchest route. The transoesophageal approach offers a low impedance, and consequently a low-energy pathway for cardioversion. PMID- 8210309 TI - Immune-related potassium-losing interstitial nephritis: a comparison with distal renal tubular acidosis. AB - Six patients with immune-related potassium-losing interstitial nephritis (IRPLIN) are described, and compared with 34 patients with immune-related distal renal tubular acidosis (IRdRTA) and 24 with familial distal renal tubular acidosis (FdRTA). Close similarities were found between IRPLIN and IRdRTA. In our experience, both syndromes are confined to postpubertal women, and are characterized by systemic features of autoimmune disease and a chronic interstitial nephritis which is probably immune-mediated and responsible for the functional tubular defects of the two syndromes. In IRPLIN, a renal potassium losing state is the main consequence (probably mediated at least in part by renin and aldosterone hypersecretion secondary to renal sodium-losing), and urinary acidification is normal or minimally disturbed; consequently there is no systemic acidosis, and the syndrome is not complicated by nephrocalcinosis or renal bone disease. In IRdRTA, the renal tubular lesion also usually causes potassium depletion, but the most prominent tubular fault is a defect in urinary acidification, which commonly causes metabolic acidosis and often leads to nephrocalcinosis and bone disease. Familial dRTA, in contrast, is equally prevalent in the two sexes and presents at an earlier age than IRPLIN and IRdRTA. Patients with FdRTA and IRdRTA have a similar urinary acidification defect and propensity to acidosis, nephrocalcinosis and bone disease. FdRTA is frequently complicated by renal potassium-losing, but hypokalaemia is less common and less profound than in IRdRTA and IRPLIN, suggesting that immune-related interstitial nephritis has a particular tendency to cause renal potassium-losing. PMID- 8210310 TI - Resuscitation decisions on a Dutch geriatric ward. AB - The use of 'do not resuscitate' (DNR) orders was analysed on a Dutch geriatric ward for a 4-month period. Of 148 admissions, 68 (58%) received a written DNR order. The use of DNR orders was significantly influenced by age (> 83 years) and the pre-arrest morbidity (PAM) index. PAM > 4 almost always resulted in a DNR order, and PAM score was the only significant contribution to DNR orders under regression analysis. The issuing of DNR orders by geriatric residents was compared with independent assessments by the other two health-care team members. In 50% of cases where significant comorbidity was zero, at least one of the team suggested a reason for a DNR order, with a mean of 1.9 reasons. The most commonly cited reasons were age (24%), depression (20%) and poor prognosis (18%). To evaluate non-patient-related factors involved in DNR decisions, we studied the involvement of patient or family in the decision, and the extent of agreement between health-care team members. Only 3% of patients and 24% of families were involved in the DNR decision. Disagreement with the residents' decisions was 20% for staff nurses and 17% for consultants. Physicians use factors besides comorbidity to make DNR decisions, and further study of such factors is necessary for the development of standardized DNR policies. PMID- 8210311 TI - Menstruation as a defense against pathogens transported by sperm. AB - Sperm are vectors of disease. During mammalian insemination bacteria from the male and female genitalia regularly cling to sperm tails and are transported to the uterus. I propose that menstruation functions to protect the uterus and oviducts from colonization by pathogens. Menstrual blood exerts mechanical pressure on uterine tissue, forcing it to shed, and delivers large numbers of immune cells throughout the uterine cavity, directly combating pathogens. The mechanisms of menstruation show evidence of adaptive design. Spiral arteries that open to the lining of the uterus trigger menstruation by abruptly constricting, which deprives the local tissue of blood, and then abruptly dilating, which causes blood to force loose the necrotic tissue. Menstrual blood flows easily, unlike blood at most wound sites, because it lacks the normal level of clotting factors. Overt (externally visible) or covert (not externally visible) menstruation has been documented in many species of primate, including Old World monkeys and apes, New World monkeys, and prosimians, as well as in various species of bat and insectivore. The antipathogen hypothesis predicts that: (1) menstruation (overt or covert) is either universal or nearly so among mammalian species; (2) if the latter, then the existence of menstruation among species varies inversely with the probability of becoming pregnant per estrous cycle (menstruation would be especially adaptive in species with significantly less than 100% probability of becoming pregnant per estrous cycle); (3) among menstruating species, the average degree of menstrual bleeding for a given species is a function of the factors affecting menstruation's costs and benefits- in particular, the degree of bleeding is positively correlated with the average body size and sexually transmitted pathogen load of that species (profuse bleeding would be especially adaptive in large-bodied species with either promiscuous breeding systems or continuous sexual receptivity); and (4) other forms of normal uterine bleeding--proestrous, periovulatory, implantation, and postpartum--also have an antipathogen function. The hypothesis presented in this article has implications for the diagnosis, treatment and prevention of uterine infection and, therefore, for the prevention of pathogen-induced infertility. The uterus appears to be designed to increase its bleeding if it detects infection: Human uteri that become infected (or otherwise inflamed) bleed more profusely, bleed on more days per cycle, and often bleed intermittently throughout the cycle. Thus artificially curtailing infection-induced uterine bleeding may be contraindicated. PMID- 8210312 TI - Damage to proteins due to the direct action of ionizing radiation. PMID- 8210313 TI - Computational challenges for macromolecular structure determination by X-ray crystallography and solution NMR-spectroscopy. PMID- 8210314 TI - Clinical research-the silent partner in dental practice. AB - For 5,000 years innovative researchers, often anonymously, have been providing dentists and their antecedents with a rich inheritance of information, techniques, and materials. The giants of dental research of the past can still serve as role models today. This paper presents a history of clinical research and relates past work to current and future trends. In the last few decades, both technical innovation and oral biology and prevention have been progressing at an accelerated rate to provide a steady influx of new answers to dental practitioners and to elicit new questions from the next generation of dental investigators. PMID- 8210315 TI - Maintenance care and supportive periodontal therapy. AB - This paper presents a review of the literature and clinical observations concerning the long-term professional care of all dental patients. Gingivitis, ubiquitous in the adult population, is often without significant consequences to the dentition; however, gingivitis may develop into periodontitis. Patients with gingivitis, therefore, should be monitored professionally, especially those patients with other risk factors (attachment loss, age, smoking, and abnormal tooth mobility). In patients without substantial attachment loss, professional examination, prophylaxis, and oral hygiene instruction should be provided once or twice a year, depending on the presence of other risk factors. All patients who have been treated for periodontitis should be recalled, after completion of treatment and a healing phase, every 3 to 4 months. Sites with active periodontitis should be re-treated. Topical use of fluorides is recommended. PMID- 8210316 TI - Common facial skin lesions in children. AB - A variety of facial skin problems are encountered in a busy pediatric dental practice. The dentist should recognize and be able to identify the more common important skin lesions. The etiology, presentation, and prognosis of acne vulgaris, impetigo, warts, molluscum contagiosum, ringworm, tinea versicolor, spider nevus, atopic dermatitis, seborrhea, herpes simplex, and lesions of child abuse are discussed. Several of these conditions require prompt referral to a pediatrician or dermatologist. PMID- 8210317 TI - Common faults in complete dentures: a review. AB - Complete-denture therapy involves a complex interplay between biologic demands and technical limitations. Success with complete-denture therapy is reportedly high. Dissatisfied denture patients, although few, do exist. This paper reviews some of the common faults reported with complete dentures. PMID- 8210318 TI - A zinc phosphate cement-luted and resin-luted fixed partial denture: a case report. AB - An innovative fixed partial denture design for restoring a posterior edentulous space is described. The distal retainer is conventionally luted with a zinc phosphate cement, and the mesial retainer is luted with a resin cement. Contingency planning, which involves placement of a nonrigid connector between the pontic and the distal retainer, allows recementation of the resin-luted segment if the resin bond fails. PMID- 8210319 TI - Replacement of missing teeth in sites with insufficient space: a case report. AB - Composite resin-retained fixed partial dentures are widely accepted as an alternative to conventional prostheses. This article describes the treatment of a patient in whom both maxillary lateral incisors were missing and space for normal sized pontics was insufficient. The incisors were replaced bilaterally with a resin-bonded fixed partial denture consisting of a cantilevered resin-bonded framework with a ceramic pontic that overlapped the mesial portion of the canine's facial aspect. This design created an esthetically acceptable prosthesis through a conservative and simple approach. PMID- 8210320 TI - Vertical root fracture: a case report. AB - A case report involving vertical root fracture in an endodontically treated mandibular left first molar is presented. Pain and extensive tissue damage occurred in the area 2 years after root canal therapy. The periapical radiograph suggested endodontic failure, and re-treatment was initially considered. However, the problem was related to a complete vertical root fracture in the distal root, which was only visible after removal of the gold crown. The tooth was extracted because severe periodontal destruction had been caused by the root fracture. PMID- 8210321 TI - Pulpal healing and dentinal bridge formation in an acidic environment. AB - This study was designed to observe the healing and bridging capacity of mechanically exposed pulps that were capped with silicate or zinc phosphate cements and biologically sealed with zinc oxide-eugenol cement to exclude bacteria. In six monkeys, Class V facial cavities with pulpal exposures were randomly distributed throughout 105 teeth, of which 80 were directly capped, 40 with silicate cement and 40 with zinc phosphate cement. Twenty of each group were filled to the cavosurface margin with the respective cement and 20 were surface sealed to the cavosurface margin with zinc oxide-eugenol cement. The remaining 25 exposures were capped with calcium hydroxide and amalgam as controls. Tissues were obtained by perfusion fixation after intervals of 21, 14, 10, 5 and 3 days. The 25 pulps capped with calcium hydroxide showed cell migration and organization at 5 days and dentinal matrix deposition at 10 days. At 3 and 5 days, all exposures in the experimental groups showed clot resolution. At 10 days, fibroblasts had stratified against the cement interface. At 14 days, pulps in both experimental groups showed new dentinal bridge formation directly adjacent to the acidic cements. The 21-day experimentally capped and sealed pulps presented healing similar to the controls. This study indicates that acidic components of silicate and Zinc phosphate cements are not directly responsible for pulpal inflammation or necrosis. The exposed dental pulp possesses an inherent healing capacity for cell reorganization and dentinal bridge formation when a bacterial seal is provided. PMID- 8210322 TI - Antibacterial activity of dentinal bonding agents. AB - The susceptibility of five bacterial species to seven dentinal bonding agents was examined in vitro. Agar diffusion tests using filterpaper disks containing 10 microL each of conditioner, primer, or resin were performed on blood agar and mitis salivarius bacitracin agar. Chlorhexidine (0.2%) was used as a positive control. After incubation, zones of inhibited bacterial growth were measured. Of all the compounds tested, Gluma cleanser and Gluma etchant showed the strongest growth inhibition for all bacterial strains. No antibacterial effect was noted for Prisma Universal Bond 2 and Superlux Universal Bond 2 systems. The primers of Gluma, Denthesive, and Scotchbond 2 displayed antibacterial activity that, in some cases, was comparable to that of 0.2% chlorhexidine. Zones of inhibition were seen for the resin materials of Scotchbond 2 and Tripton with Streptococcus mutans, Streptococcus sanguis and Actinomyces viscosus. No inhibition was seen after these resins were cured, whereas the antibacterial effect of XR-Bond on S sanguis and A viscosus was not affected by light curing. PMID- 8210323 TI - Effects of curing tip distance on light intensity and composite resin microhardness. AB - Recently, simple radiometers for measuring the intensity of dental curing lights have been introduced. This study examined the relationship among light intensity measurements by three radiometers, distance of curing tip from composite resin, and resin polymerization (as indicated by microhardness). Light intensity measurements, which decreased with increasing distance from the curing tip, were strongly correlated with composite resin hardness. Reduced light intensity produced softer composite resin, particularly on the bottom of specimens (2-mm depth). The different radiometers provided similar indications of the changes in light intensity at various curing distances. PMID- 8210324 TI - The fragmentation of 670A MeV neon-20 as a function of depth in water. III. Analytical multigeneration transport theory. AB - This is the final report of a detailed study of the interaction of 670A MeV neon ions with water, used as a presumed tissue-equivalent target. A first comparison of the data with theoretical fluence spectra predicted by the one-generation heavy-ion transport code HZESEC was reported previously. In the present article, subsequent nuclear interactions of the fragment are taken into account, using the LBLBEAM multigeneration heavy-ion transport code, which incorporated new features and modifications intended to address some of the approximations made in the previous calculation. The LBLBEAM code uses the method of characteristics and an iterative procedure to solve a one-dimensional Boltzmann transport equation for the first through third successive generations of nuclear reaction products; it includes a recent version of the semiempirical model used to derive nuclear interaction cross sections. The stopping power used for the theory was calculated in the same way that experimental time-of-flight and energy-loss data are converted to obtain a comparison independent of stopping power; accordingly, good agreement was found between calculated and measured neon fluence spectra in the Bragg peak region. Multiple scattering effects were considered separately for each isotope in the present work. Acceptance factors were calculated as previously, assuming that all projectile fragments originate from the first nuclear interaction. The results show that lower-mass isotopes can account for the high-LET portions of the spectrum in measured fluence spectra. Third generation products become increasingly important as a source of lighter fragments for depths comparable with the primary particle mean free path, accounting for between one-third and one-half of carbon and lighter particles near the Bragg peak; higher-order interactions were negligible for the detector geometry and material thicknesses examined. Agreement between measured and calculated fluence spectra is 30% (20% for integral fluences). Inclusion of hydrogen, helium, and lithium fragments improves agreement between calculated and measured RBE values for spermatogonial cell survival, but tertiary particle acceptance and track structure effects need to be understood in greater detail to predict RBE accurately. PMID- 8210325 TI - Continuous irradiation of beagles with gamma rays. AB - The effects of exposure to 60Co gamma rays for the duration of life on mortality patterns in beagles were investigated. Doses of 3, 7.5, 18.8, 37.5, 75, 127.5, 262.5, 375, or 540 mGy were delivered over a 22-h day 7 days a week. Hazard models with time-dependent covariates were used to identify radiation-related trends in mortality. Hematopoietic failure occurring early in life was positively associated with the accumulated dose and the rate at which the dose was delivered. The risk of death from causes other than cancer that occurred later in the life span also depended on accumulating dose and dose rate but was lower than the cancer risk. Once an animal survived long enough to die from cancer, failure times depended only on the accumulating dose. The slope 1 and slope 2 boundary in a Gompertz plot historically used to identify the transition between dose rate and total dose effects was also found to distinguish between late-occurring deaths associated with tumor or nontumor events. PMID- 8210326 TI - Analysis of somatic cell mutations at the glycophorin A locus in atomic bomb survivors: a comparative study of assay methods. AB - The glycophorin A (GPA) assay for in vivo somatic cell mutations was performed on blood samples from 39 survivors of the atomic bomb at Hiroshima. Parallel analyses were performed at two laboratories using three different GPA assay methods to enumerate cells lacking expression of either the M- or N-allele of GPA. All assay methods yielded significant dose-dependent increases in hemizygous GPA variant cell frequencies (VFs) and smaller increases in homozygous VFs. The slopes of the fitted linear dose-response functions did not differ significantly among assay methods used in the present study, or from slopes obtained in a study reported previously. The version of the assay described most recently (BR6) appears best suited for future studies because the assay has a higher precision than earlier methods. Variant frequencies from different assay methods measuring the same variant cell type agreed with each other better than with the estimated dose, suggesting that the imprecision in the assay is not primarily responsible for VFs that differ from the fitted dose response. Consistent deviations from the dose response were seen for some individuals, suggesting either errors in dose estimates for these individuals or interindividual differences in susceptibility or other exposures. For the study population as a whole, however, discrepancies between assays for M-loss and N-loss variants suggest stochastic factors may have an important effect on individual VFs for A-bomb survivors. PMID- 8210327 TI - Radiation dose-fractionation and dose-rate relationships for long-term repopulating hemopoietic stem cells in a murine bone marrow transplant model. AB - Fractionated and low-dose-rate total-body irradiation (TBI) were compared with single-dose high-dose-rate TBI for induction of long-term hemopoietic chimerism in a murine syngeneic bone marrow transplantation model. At 5 months after TBI and bone marrow transplantation, the degree of stable blood chimerism was determined from the proportion of stem cell-derived donor (B6-Gpi-1a) and host (B6-Gpi-1b) blood erythrocytes. This end point was used to construct radiation dose-response curves for long-term donor marrow engraftment corresponding to ablation of primitive bone marrow stem cells of the host. Increasing dose fractionation and decreasing dose rate had the effect of restoring host hemopoiesis and required higher TBI doses for equal donor engraftment. Most of the dose recovery occurred within the first 6 h between fractions, consistent with the kinetics of sublethal damage repair. The late chimerism data were fitted to the linear-quadratic model using indirect and direct analysis for a fixed threshold response. Both analyses gave relatively low alpha/beta ratios (below 2 Gy), within the range normally seen in late-responding tissues. The dose-rate data gave a repair half-time of 2 h as estimated by the incomplete-repair model. These estimates contrast with the much higher alpha/beta values and lower repair half-times derived from acute hemopoietic failure as indicated by LD50/30, with the implication that separate target cell populations with differing radiosensitivities are involved in these two bone marrow end points. PMID- 8210329 TI - Radiation-induced apoptosis measured in TK6 human B lymphoblast cells using the comet assay. AB - The comet assay, a sensitive method of measuring DNA strand breaks in individual cells, is also capable of identifying apoptotic cells which contain highly fragmented DNA. This method requires embedding cells in agarose, lysing cells to remove proteins, and providing a brief exposure to an electric field to allow broken pieces of DNA to migrate. TK6 human B lymphoblast cells undergo fragmentation which is dependent on both time after irradiation and radiation dose. While some TK6 cells undergo apoptosis within 2 h after irradiation, the fragmentation rate increases approximately 10 h after exposure to radiation doses of 2.5 to 15 Gy. Results confirm that apoptosis is a very rapid event since few cells with intermediate amounts of DNA damage were detected. The comet assay detected apoptotic TK6 cells much earlier than a flow cytometry method. PMID- 8210328 TI - Radiorecovery activity of manganese(III)2(II)(mu 3-O)-(mu-3,5 diisopropylsalicylate)6. AB - Manganese(III)2(II)(mu 3-O)(mu-3,5-diisopropylsalicylate)6 [Mn3(O)(3,5-DIPS)6] was used to treat female C57BL/6 mice irradiated with LD50/30 doses of gamma rays and examine the possibility that treatment after irradiation increases survival. Female C57BL/6 mice were treated with 0, 10, 20, or 40 mumol Mn3(O)(3,5-DIPS)6/kg of body mass 1 or 3 h after irradiation. Treatment with 40 mumol/kg 1 or 3 h after irradiation produced survivals of 72 or 92%, respectively, increases of 29 or 130% in comparison with 56 or 40% survivals in the respective vehicle-treated groups. These data support the hypothesis that Mn3(O)(3,5-DIPS)6 is an effective radiorecovery agent. PMID- 8210330 TI - Questions about radiation and risk estimates that remain after BEIR V. PMID- 8210331 TI - Important unanswered questions concerning radiation risk estimates. AB - While the most important radiobiological questions at present can be stated simply, arriving at the answers requires the development of a broad base of understanding to which collaborative interdisciplinary efforts that use a variety of techniques will make important contributions. In spite of the range of questions that remain unanswered, we probably know more about the effects of radiation than any other environmental agent. A sound and well-planned research program into the mechanisms of radiation carcinogenesis can help in many predictable ways. It will provide data needed for setting protection standards, of course, but it will also play a vital role in solving some of the enigmas of the mechanisms of carcinogenesis. In addition, the information gained by the approach focused on basic science will ultimately provide much better methods for extrapolating from cellular and animal studies to health effects in humans and thus for developing sound, science-based radiation risk estimates. PMID- 8210332 TI - Risk estimates for genetic effects of ionizing radiation. PMID- 8210333 TI - The pulmonary response to sublethal thoracic irradiation in the rat. AB - An animal model of radiation-induced lung disease was established using male Wistar rats given sublethal bilateral thoracic irradiation (15 Gy). The rats were studied for up to 20 weeks and compared to sham-irradiated controls. Three distinct syndromes were identified. Two weeks after irradiation there was an increase in wet lung weight without an increase in dry lung weight. Interstitial edema was confirmed ultrastructurally, but aside from minor abnormalities of endothelial cells, both capillary and alveolar basement membranes were intact and there was no alveolar protein leak. At 4 weeks after irradiation, there was an abrupt increase in both wet and dry lung weights, as well as intra-alveolar macrophages, lymphocytes, polymorphs, and protein. These changes persisted for periods of up to 8 weeks. Electron microscopy at 4 weeks revealed prominent interstitial edema and severe endothelial cell damage. There was patchy thickening of the cytoplasm of type I cells as well as some cells which appeared to be transforming from type II to type I cells, suggesting previous epithelial denudation. Mast cell density increased in perivascular and peribronchial areas from 4 weeks, and this and parenchymal mast cell density peaked at 7 weeks. The total collagen content of the lungs (determined biochemically) rose by up to 50% above control values from 5 weeks after irradiation, the bulk of the increase having occurred by 12 weeks. Further increases up to 20 weeks were similar to that seen in growing control animals. Collagen deposition (as defined by electron microscopy and Picrosirius polarization) was prominent in peribronchial and perivascular areas in all animals, but in alveolar walls it was increased severalfold above controls by 20 weeks after irradiation. In summary, this model provides sequential changes of interstitial edema, alveolitis, and interstitial fibrosis which can be studied independently. The temporal relationship between the appearance of mast cells and increased collagen deposition supports the hypothesis that mast cells are intimately related to the development of fibrosis. PMID- 8210334 TI - The effect of steroids on radiation-induced lung disease in the rat. AB - We have used a model of bilateral radiation-induced lung disease in the rat to study the effects of corticosteroids. This model is characterized by interstitial edema at 2 weeks after radiotherapy followed by florid alveolitis with an alveolar protein leak which peaks at 4 weeks. Mast cell density peaks at 7 weeks, and there is a progressive increase in lung collagen (fibrosis) from 5 to 20 weeks. Intraperitoneal corticosteroids or saline were given at the time of irradiation or sham irradiation (protocol 1), every second day during weeks 3 and 4 (protocol 2), or three times weekly during weeks 3 to 8 (protocol 3). In protocol 1, steroids protected the lung from interstitial edema at 2 weeks, delayed the alveolitis without reducing its intensity, and significantly reduced the alveolar protein leak. However, radiation fibrosis was not reduced at 20 weeks. Longer steroid administration (protocol 2) suppressed the alveolar protein leak and delayed and significantly reduced the severity of the inflammatory cell response. Although the tissue mast cell and fibrotic responses were suppressed during and for at least 3 weeks after steroids, the ultimate fibrotic reaction was the same in both irradiated groups. In protocol 3, steroids suppressed the alveolitis and delayed the rise in tissue mast cell density, but did not affect the fibrotic response at 20 weeks. These studies suggest that steroids can suppress the alveolitis provided they are used throughout the period of alveolitis. Although they also delay the tissue mast cell response to radiation, the ultimate fibrosis is not altered. This provides further evidence for the dissociation of alveolitis and fibrosis after lung irradiation and has potential implications for management of radiation-induced lung disease in humans. PMID- 8210335 TI - Stable chromosome aberrations among A-bomb survivors: an update. AB - Analysis of data on stable chromosome aberrations collected between 1968 and 1985 by the Radiation Effects Research Foundation (RERF) on 1703 individuals exposed to A-bomb radiation in Hiroshima and Nagasaki, Japan, reveals different dose response relationships in the two cities, as well as significant effects of both time of assay and age at exposure. In Hiroshima, the proportion of cells with aberrations increased by 0.080 per sievert at low doses, assuming a constant neutron radiation RBE of 10 relative to gamma radiation, for assays performed during the latest period (1981-1985). In Nagasaki, the low-dose increase was 0.0126 per sievert. There was evidence that radiation exposure was more effective for producing stable aberrations at some younger ages at exposure, although the interpretation of this interaction is difficult. Modeling neutron and gamma-ray components of dose separately in a way which allows the neutron RBE to vary with dose yielded an estimated low-dose limiting value of RBE of 707 (95% confidence bound 200-infinity), with a low-dose response of approximately 0.008 aberrations per sievert. This RBE is much higher than the published RBEs for induction of aberrations in vitro. The high estimated RBE and the differences in dose response by city both are suggestive of systematic dose estimation errors in which either neutrons were underestimated in Hiroshima or gamma rays were overestimated in Nagasaki. PMID- 8210336 TI - Release of interleukin-1 by human alveolar macrophages after in vitro irradiation. AB - Therapeutic thoracic irradiation may induce two late pulmonary injury syndromes: radiation pneumonitis and subsequent pulmonary fibrosis. The alveolar macrophage has been considered a radioresistant cell and not a target cell involved in the pathogenesis of either type of radiation-induced lung injury. Alveolar macrophage derived cytokines, including interleukin-1 (IL-1) and tumor necrosis factor (TNF), have been demonstrated to participate in inflammatory and fibrotic responses in the lung after various other types of lung injury. To evaluate whether the release of cytokines by alveolar macrophages is induced by radiation doses used clinically, alveolar macrophages recovered from nonsmoking volunteers were exposed in vitro to a single dose of 2 Gy and then maintained in culture for 18 h. Culture supernatants and cell lysates were then recovered and analyzed for IL-1 alpha and IL-1 beta by radioimmunoassay. Supernatants of irradiated alveolar macrophages contained significantly increased amounts of IL-1 alpha (P < 0.04) and IL-1 beta (P < 0.02) as well as total IL-1 (IL-1 alpha and IL-1 beta) (P < 0.02) compared to nonirradiated alveolar macrophages. Cell lysates of irradiated alveolar macrophages also contained increased amounts of IL-1 alpha and IL-1 beta, although differences from controls were not significant. The finding of increased release of IL-1 by alveolar macrophages after exposure to a single, clinically relevant dose of radiation suggests that the function of human alveolar macrophages is likely altered during therapeutic use of thoracic irradiation. Whether this release of IL-1 by alveolar macrophages contributes to early lung inflammation induced by thoracic irradiation is unclear. PMID- 8210337 TI - Acute effects of X irradiation on the function of rat salivary glands. AB - Radiation-induced damage to salivary glands has been recognized for over 80 years. However, the mechanisms responsible for the destruction of gland parenchyma are still not known. The purpose of this study was to describe alterations in salivary function in the rat within the first 24 h after irradiation. Saliva was collected from the parotid and submandibular glands during radiation treatment and at four times (0.5, 1, 4, and 24 h) after 15 Gy X irradiation delivered to the head and neck. Total body weight, submandibular gland weight, and food and water intake were monitored and the total protein, sodium, and potassium content of the salivas was analyzed. The effects of radiation on salivary glands of the rat could be demonstrated by 24 h. Parotid salivary flow was reduced and the sodium concentration was significantly less than that in control animals. Submandibular gland weights declined markedly by 24 h. These effects appear to be influenced significantly by the animals' limited intake of food and water during this period, as well as the anesthesia administered. PMID- 8210338 TI - Interlaboratory comparison of the effects of radon on L5178Y cells: dose contribution of radon daughter association with cells. AB - The cytotoxic and mutagenic effects of radon and its progeny were compared in murine lymphoblast L5178Y-R16 cells after exposure at three institutions. The cells were exposed to 222Rn at Case Western Reserve University (CWRU) and Pacific Northwest Laboratories (PNL) and to 212Bi, a decay product of 220Rn, at the University of Chicago (UC). The dose to the cell nucleus was calculated using a dosimetric model which addressed both the contribution of the dose from the radioactivity in the medium and that associated with the cells. The dose-response curves for cell survival showed D0's of 0.30 Gy at CWRU, 0.20 Gy at PNL, 0.37 Gy for chelated 212Bi, and 0.13 Gy for unchelated 212Bi. Induced mutant frequencies at the thymidine kinase locus at the 37% survival level were 1470 x 10(-6) at CWRU, 1518 at PNL, and 2414 x 10(-6) at UC using combined results for chelated and unchelated 212Bi. The variation between institutions was greater than obtained in a previous interlaboratory comparison of the effects of radon on CHO cells. Since less radioactivity was associated with CHO cells than L5178Y cells, we have concluded that the variation between institutions in the case of L5178Y cells is caused by the differences in cell-associated radioactivity and errors related to the measurement of this parameter. PMID- 8210339 TI - Cytotoxic and mutagenic effects of radon and radon daughters on murine L5178Y lines differing in DNA repair. AB - The effects of 222Rn were measured in mouse L5178Y (LY) lymphoblasts that differ in repair capabilities. Line LY-S1 is deficient in the repair of X-radiation induced DNA doublestrand breaks, while lines LY-R16 and LY-R83 are presumed to be deficient in the excision of UV-radiation-induced pyrimidine dimers. Line LY-R83 is hemizygous while the other two lines are heterozygous at the thymidine kinase (tk) locus. After exposure to radon the D0's were found to be very similar for the three lines (0.30-0.31 Gy), whereas for X radiation the D0 for line LY-S1 is lower (0.7 Gy) than that for the two LY-R lines (1.3 Gy). Mutant frequencies at the tk locus were higher per gray after treatment with radon than X radiation, but at equitoxic doses the mutant frequencies were similar for X and alpha particle radiation. A low radon-induced mutant frequency was observed for the hemizygous line, in agreement with the hypothesis that multilocus lesions were induced by the alpha-particle radiation and that mutants bearing intergenic lesions were not recovered in the TK+/- line. The entire active tk allele was lost by 81% of the TK-/- mutants of line LY-R16. In lines LY-S1 and LY-R16, 39 43% of the TK-/- mutants exhibited loss of galactokinase activity, indicating that the mutational lesion inactivating the tk gene frequently extended to the neighboring galactokinase gene. PMID- 8210340 TI - Increased expression of the epidermal growth factor receptor in human epidermal keratinocytes after exposure to ionizing radiation. AB - The effect of exposure of human epidermal keratinocytes to ionizing radiation, both in vivo and in vitro, on the expression of the epidermal growth factor receptor (EGF-R) was studied on the protein, mRNA, and functional levels. Quantitative fluorometry of short-term organ cultures incubated with a monoclonal antibody against human EGF-R revealed a dose-dependent increase of EGF-R expression 24 h after irradiation with 4 and 6 Gy, with an additional increase after 48 h. In biopsy specimens from patients undergoing radiation therapy a markedly increased expression could be determined by quantitative fluorometry during radiation therapy which wa still considerably above the baseline level 4 weeks after termination of treatment. Radioligand binding assays demonstrated a 50% increase in 125I-EGF binding to primary keratinocytes and A431 cells, at doses of 1 Gy, with a further increase after 72 and 96 h. Northern blots were performed with total RNA from two human epidermal cell lines (SCLII and A431). In A431 cells, increased EGF-R transcript levels could be detected 48 h after irradiation. In cells of the SCLII cell line, EGF-R expression was not affected by irradiation. These results were confirmed by semiquantitative polymerase chain reaction of primary cultured keratinocytes, demonstrating an increase of transcripts of EGF-R 24 h after irradiation with single doses of 6 Gy. Thus exposure to ionizing radiation leads to an increased expression of functionally intact EGF-R in human keratinocytes, at the protein and mRNA levels, both in vitro and in vivo; we hypothesize that this effect is part of a stress program of epidermal cells in response to ionizing radiation, ensuring rapid repopulation of irradiated areas. PMID- 8210341 TI - Visualization of nonreciprocal chromosome exchanges in irradiated human fibroblasts by fluorescence in situ hybridization. AB - A long-standing controversy in radiation cytogenetics is the precise mechanism for the formation of chromosome exchanges. The classical breakage-and-reunion hypothesis suggested by Stadler and developed by Sax was challenged in 1959 by Revell, who proposed that radiation produced an "unstable lesion" which could interact with another such lesion to form an exchange. A difference between the predictions of these two theories is that the breakage-and-reunion hypothesis would allow the two broken ends of a chromosome to join with contemporary broken ends in different chromosomes, thereby producing nonreciprocal exchanges involving more than two chromosomes. This would not occur according to the Revell theory, which demands pairwise commital to the exchange. The ability to "paint" a whole chromosome using fluorescence in situ hybridization allows a discrimination between reciprocal and nonreciprocal chromosome exchanges. We scored metaphases in AG1522 human fibroblasts irradiated in G1 phase with 6 Gy and hybridized to chromosomes 1, 4, or 8. Of the complete exchanges involving one of these chromosomes, 26% were found to possess either one or three centromeres in the exchange pair. Since we could rule out any significant contribution of complex exchanges (i.e., those involving more than one break per chromosome), these one- and three-centromere exchange pairs must have arisen from a nonreciprocal exchange. Because an equal number of nonreciprocal exchanges would be expected to have a total of two centromeres, this suggests that approximately 50% of all exchanges at this dose were nonreciprocal. These data support the breakage-and reunion hypothesis and are incompatible with the standard form of the exchange hypothesis of Revell. PMID- 8210342 TI - Radiation-induced DNA damage in tumors and normal tissues. I. Feasibility of estimating the hypoxic fraction. AB - It is well known that the type and quantity of DNA damage produced by ionizing radiation depend on the oxygen concentration around the DNA. For example, in irradiated mammalian cells, both a decrease in the DNA strand break efficiency and the induction of DNA-protein crosslinks (DPCs) occur as the extracellular oxygen concentration is decreased below 1%. In the study reported here, the feasibility of estimating the hypoxic fraction of irradiated tumors and normal tissues was investigated by measuring the single-strand scission factor, the DNA protein crosslink factor, and the amount of DNA remaining on polycarbonate filters after elution with approximately 24 ml of tetrapropylammonium hydroxide at pH 12.3 without proteinase K (PK) in the lysis solution. In anesthetized air breathing Fisher 344 rats, no radiation-induced DPCs were detected in either cerebellar neurons or cells of subcutaneous (sc) 9L tumors when the DNA was assayed at approximately one half-time of repair after doses < or = 15 Gy. Within 10 min after anesthetized rats were killed, the maximum decrease in the radiation induced strand break efficiency and the maximum formation of radiation-induced DPCs occurred in both cerebellar neurons and sc 9L tumors. When irradiated cerebellar neurons or sc 9L tumor cells from air-breathing and dead rats were mixed to simulate hypoxic fractions of 0, 10, 25, 50, 75, and 100%, only the percentage of the DNA retained on the filter after approximately 24 ml of elution without PK in the lysis solution was a linear function of the simulated hypoxic fraction after doses of both 15 and 2 Gy. At 15 Gy, the linear function was identical for 9L cells in tissue culture, sc 9L tumor cells, and cerebellar neurons. In addition, the slope, but not the intercept, of the linear function appeared to be independent of dose from 2 to 15 Gy. Consequently, if the dose and the amount of strand break repair are kept relatively constant, the linear function appears to depend primarily on radiation chemistry events, rather than the biological properties of the irradiated cells. Moreover, the data suggest that this assay can measure a hypoxic fraction of < or = 10% after a conventional radiotherapy dose of 2 Gy, provided sufficient material is available for analysis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8210343 TI - Effects of 210Po alpha particles on survival and preneoplastic transformation of primary rat tracheal epithelial cells irradiated while in suspension or in the intact tissue. AB - Rat tracheal epithelial cells exhibited exponential cell killing when exposed to 210Po alpha particles as single cell suspensions or in the intact tissue. Survival of cells in the intact tissue was not significantly different from that observed with cell suspensions. Comparison of survival of cells exposed in suspension to 300 kVpX rays yielded an RBE of 6.3. Measurements of basal cell nuclei were used to determine that a single traversal of a cell nucleus had a high probability of causing cell inactivation. This was also observed in mink lung cells and CHO cells exposed in an identical manner. There were no significant increases in frequencies of preneoplastic transformation observed for a range of exposures (0.0007 to 0.05 alpha particles/micron2). Examination of intact tracheal transplants which were irradiated with alpha particles also failed to reveal any preneoplastic or neoplastic changes. PMID- 8210344 TI - Mutation induction by different dose rates of gamma rays in near-diploid mouse cells in plateau- and log-phase culture. AB - Induction of mutation to 6-thioguanine resistance was studied in cultured near diploid mouse cells (m5S) in plateau and log phase after exposure to gamma rays at dose rates of 30 Gy/h, 180 mGy/h, or 13 mGy/h. In plateau-phase culture, lowering the dose rate from 30 Gy/h to 13 mGy/h resulted in an increase in cell survival and a marked decrease in induced mutation frequency. On the other hand, in the log-phase culture, the magnitude of the dose-rate effects was not as marked as in the plateau-phase culture, particularly within a dose range below 5 Gy. These results, together with those indicating the inverse dose-rate effects in growing mouse leukemia cells (Radiat Res. 115, 273-280, 1988), demonstrate the significant influence of cell growth that takes place during protracted irradiation, particularly for the induction of mutation. PMID- 8210345 TI - Screening for colon cancer: controversies and recommendations. AB - Colorectal cancer is the second most common cause of overall cancer mortality in the United States. This article review pertinent clinical and policy issues, details current colorectal cancer screening concepts, summarizes American College of Radiology achievements to date, and outlines projects in the next phase of the effort. PMID- 8210346 TI - Ischemic bowel disease. AB - The pathophysiologic events occurring in the ischemic process are described so that radiologic findings are understood rather than memorized. Depending on the underlying disease, the ischemic process can lead almost instantly to infarction or may be so indolent that years or even decades of low-grade ischemia may occur. The spectrum is discussed and illustrated. PMID- 8210348 TI - Appearances of the postoperative alimentary tract. AB - In summary, patients who have had alimentary tract operations are looked upon by most radiologists as a travail rather than a challenge. This article has reviewed common operations and has given some definite guidelines to ensure accurate radiologic diagnoses of patients who have had even complicated alimentary tract surgery. PMID- 8210347 TI - Radiologic evaluation of suspected gastrointestinal perforations. AB - Perforation of the alimentary tract may occur spontaneously in various gastrointestinal diseases or develop due to an ingested foreign body, iatrogenic complication, and blunt or penetrating injuries. The detection of extraluminal air on radiographs of the chest or abdomen is often the initial clue to the diagnosis. It may not, however, be visible when the perforation is small, rapidly sealed, or well contained. Further evaluation by special radiographic techniques, gastrointestinal studies using contrast media, or CT examination can demonstrate the site and nature of the perforation. This article reviews the clinical features and methods for radiologic assessment of suspected perforations involving the upper gastrointestinal tract, small bowel, or colon and rectum. PMID- 8210349 TI - Imaging of recurrent carcinoma of the gastrointestinal tract. AB - Computed tomographic scanning is currently the main imaging modality used to detect recurrent cancer of the gastrointestinal tract. Additional studies such as MR imaging, ultrasound, and immunoscintigraphy provide complementary information. Further research is needed so that these studies can be applied in a cost effective manner that has a positive impact on clinical outcomes. PMID- 8210350 TI - Contrast evaluation of the pharynx and esophagus. AB - Swallowing requires the coordinated action of the alimentary tract from the oral cavity to the gastroesophageal junction. Any structural or functional abnormality along this pathway will interfere with swallowing. The "barium swallow" or pharyngoesophagogram requires examination of the oral cavity, pharynx, esophagus, and gastric cardia. PMID- 8210351 TI - Role of the barium enema in colorectal carcinoma. AB - Colorectal carcinoma is the second most common cancer that occurs in women and men. To better appreciate the role of the barium enema in the evaluation of colorectal carcinoma, an understanding of its epidemiology, pathologic development, and current methods of detection is needed. Following review of these aspects of colorectal carcinoma, the barium enema is discussed more thoroughly regarding examination techniques, radiologic evaluation of colonic neoplasms, quality of the examinations, and radiologic efficacy. PMID- 8210352 TI - Inflammatory conditions of the stomach and duodenum. AB - Upper gastrointestinal inflammatory processes are exceedingly common and have a wide spectrum of causes and manifestations. The broad category of acid-peptic disease incorporates the most common and important conditions. Concepts of pathophysiology of gastritis and duodenitis and their relationship to ulcers and neoplasm continue to evolve. The role of infection, especially H. pylori, remains under intense investigation. The spectrum of gastroduodenal inflammation in the immunocompromised host continues to expand and becomes increasingly important. A variety of granulomatous processes, both infectious and idiopathic, involve the upper gastrointestinal tract in overlapping patterns. Although investigation of ulcers and syphilis occupied the attention of the earliest gastrointestinal radiologists, related problems continue to challenge today's radiologic imagers, clinicians, and investigators. PMID- 8210353 TI - The abdominal plain film. What will be its role in the future? AB - Conventional imaging studies are now being closely scrutinized for clinical utility. Some, like the skull film, are obsolete while others have secured an enduring place for themselves. The plain film of the abdomen occupies a middle ground with its role supplanted by other studies for many conditions but its value is still appreciated for the assessment of intestinal obstruction and perforation. Today, its special capabilities for the evaluation in diverticulitis and iron therapy have been under emphasized. In the future, the plain film will have a narrower focus but when combined with CT both examinations can be enhanced. PMID- 8210354 TI - Abdominal complications in organ transplant recipients. AB - A variety of intraabdominal complications are associated with organ transplantation. These include inflammatory changes involving the bowel, liver, and pancreas and range from technical complications associated with the surgery to organ rejection, opportunistic infections, and an increased risk of de novo malignancy in transplantation patients. PMID- 8210355 TI - Metastatic disease involving the gastrointestinal tract. AB - Secondary involvement of the gastrointestinal tract by malignancies is encountered frequently. It usually reflects a poor prognosis because it is often multicentric and associated with metastases in other organs. Any therapy is usually palliative. Because of this, conventional barium studies or CT is sufficient for diagnosis and can obviate further studies. PMID- 8210356 TI - Radiologic evaluation of constipation and anorectal disorders. AB - This article has outlined the orderly radiographic approach to evaluating the patient who presents with constipation or other anorectal complaints. Defecography alone provides only a visual record of events taking place during defecation, and it seems likely that further understanding of the pathophysiology will require manometric, electromyographic, and proctographic data in those patients. Defecography is potentially more available than these other techniques because every hospital has a fluoroscopy suite. Studies that relate the proctographic findings with other physiologic studies are underway and necessary. More studies relating pre- and postoperative defecography with clinical results are needed. PMID- 8210357 TI - Practical approaches to pediatric gastrointestinal radiology. AB - Radiologic evaluation of the pediatric gastrointestinal tract requires knowledge of the specific problems acutely afflicting the gastrointestinal tract in children and the specialized approaches required for accurate radiologic diagnosis. Efficacious radiologic evaluation and accurate diagnosis are possible only when the radiologist is aware of the presence and significance of clinical findings. The radiologist must take an active role in formulating a presumptive diagnosis and determining the best course of radiologic examination. Careful correlation of clinical and radiologic findings is necessary to assure accurate diagnosis and appropriate treatment. PMID- 8210358 TI - Current role of MR imaging in the staging of adenocarcinoma of the prostate. AB - Surgical cure of adenocarcinoma of the prostate (ACP) is possible in over 80% of cases when the disease is confined to the gland capsule. The endorectal probe for magnetic resonance (MR) imaging has increased resolution of the prostate gland and capsule, which has improved the sensitivity and specificity for staging ACP (.65 sensitivity, .69 specificity for body coil; .87 sensitivity, .85 specificity for the endorectal coil). Normal glandular regions in the peripheral zone and central zone have significantly higher citrate levels than ACP and fibromuscular and fibrous benign prostatic hyperplasia at proton spectroscopy. ACP has a higher phosphomonoester-phosphocreatine ratio than normal glandular tissue at phosphorus spectroscopy. The combination of endorectal coil MR imaging for local spread, and body coil MR imaging for advanced disease, makes MR imaging the premier imaging modality for the preoperative staging of ACP. PMID- 8210359 TI - Neural networks at the crossroads. PMID- 8210360 TI - Self-referral medicine: a growing consensus for action. PMID- 8210361 TI - The "cost-effectiveness" of radiology and radiologists. PMID- 8210362 TI - Self-referral in private offices for imaging studies performed in Pennsylvania Blue Shield subscribers during 1991. AB - PURPOSE: To define the frequency of physician self-referral for diagnostic imaging studies. MATERIALS AND METHODS: High-volume radiographic (n = 65) and ultrasound (US) (n = 29) procedural codes in claims filed by Pennsylvania Blue Shield subscribers were analyzed to determine private-office (nonhospital) utilization of these examinations by radiologists and nonradiologists during 1991. A total of 787,703 radiographic and 159,281 US claims were filed. RESULTS: Nonradiologists self-referred 550,878 radiographic examinations (69.9%) and 99,931 US examinations (62.7%). Patterns of utilization varied considerably by anatomic category: The imaging studies with the highest rates of utilization by nonradiologists were skeletal radiography, vascular US, and obstetric and pelvic US. Aggregate reimbursement allowance by Pennsylvania Blue Shield for all examinations in these 94 codes was approximately $68 million, of which $44 million (65%) went to non-radiologists. PMID- 8210363 TI - Use of radiology in U.S. general short-term hospitals: 1980-1990. AB - PURPOSE: To determine changes in usage of radiologic services between 1980 and 1990. MATERIALS AND METHODS: Complete data were obtained from 107 (42%) hospitals and incomplete data from eight (3%) (total survey response rate, 45%). Information was requested about the number of general radiologic examinations; specific modalities of computed tomography (CT), magnetic resonance (MR) imaging, nuclear medicine, and ultrasonography (US); and numbers of CT, MR imaging, and US machines. RESULTS: The number of general radiologic examinations in hospitals increased from approximately 126 million to 179 million (> 42%); for CT, from 3.6 million to 13.3 million; nuclear medicine, from 6.4 million to 7.4 million; and US, from 4.3 million to 11.8 million. MR imaging examinations performed during 1990 were estimated at 1.8 million. CONCLUSION: The number of radiologic examinations performed in U.S. hospitals increased by 30%-60% between 1980 and 1990, mainly due to increased usage of CT, MR imaging, and US. PMID- 8210364 TI - Irradiation of the cervix uteri: value of unenhanced and contrast-enhanced MR imaging. AB - PURPOSE: To analyze the value of magnetic resonance (MR) imaging after radiation therapy for cancer of the cervix. MATERIALS AND METHODS: Eighty-nine MR images were retrospectively studied in 69 patients aged 46.3 years +/- 11.5. MR findings of tumor recurrence and irradiation changes were correlated with time after radiation therapy; paracentral radiation dose (dose to point A); and in patients with pretreatment images, primary tumor size and stage. RESULTS: Overall accuracy of MR in diagnosis of tumor recurrence was 78% (positive predictive value, 65%; negative predictive value, 97%). In MR examinations less than 6 months after the beginning of radiation therapy, accuracy (69%) and specificity (46%) were significantly lower than in examinations more than 6 months later (88%, P = .0032; 81%, P = .0166, respectively). Comparison of pre- and posttreatment MR findings and knowledge of stage or initial tumor size did not affect MR results. CONCLUSION: Overall, diagnosis was best with unenhanced T2-weighted images, but in patients with adnexal or pelvic sidewall recurrence and in patients with treatment complications (eg, fistula formation), contrast enhancement did help. PMID- 8210365 TI - Routine helical CT of the abdomen: image quality considerations. AB - PURPOSE: Both helical and nonhelical abdominal computed tomographic (CT) scans were obtained to compare image quality, study the effect of patient size and collimation, and compare the frequency of visualization of normal abdominal structures. MATERIALS AND METHODS: The study group consisted of 60 consecutive patients with clinically suspected metastatic malignancy. RESULTS: Both helical and nonhelical image quality was excellent, with equal mean image quality scores of 4.1 on a 5-point scale. In patients weighing more than 175 lb (79 kg), both helical and nonhelical image quality degraded equally when 5-mm collimation was used; 10-mm collimation resulted in excellent image quality, regardless of patient size. Small in-plane structures (eg, renal arteries, renal veins, pancreatic duct) were seen best on helical scans. With the addition of retrospectively reconstructed overlapping images, improvement in visualization of these structures was statistically significant. CONCLUSION: Helical CT scanning should be the preferred means of acquiring routine abdominal CT images. PMID- 8210366 TI - Hepatic metastases: detection with multisection FLASH MR imaging during gadolinium chelate-enhanced arterial portography. AB - PURPOSE: To determine the feasibility and sensitivity of multisection fast low angle shot (FLASH) magnetic resonance (MR) imaging in the depiction of hepatic metastases. MATERIALS AND METHODS: The cases of 10 patients with 39 surgically proved hepatic metastases were prospectively evaluated. After unenhanced T1- and T2-weighted spin-echo (SE) and FLASH imaging, 4 mL of a 0.5 mol/L solution of a gadolinium chelate (tetraazacyclododecanetetraacetic acid) was injected into the superior mesenteric artery during FLASH imaging in a single breath-holding period. RESULTS: No side effects were noted. With multisection FLASH MR arterial portography, tumor-to-liver contrast-to-noise ratio (34.5 +/- 4.4) was significantly increased compared with unenhanced MR imaging. Sensitivity was 74% (29 of 39) for combined SE and multisection FLASH imaging and 95% (37 of 39) for multisection FLASH MR arterial portography (McNemar test, P < .02). CONCLUSION: Multisection FLASH MR arterial portography is a safe, feasible, and sensitive technique with which to detect hepatic metastases. PMID- 8210367 TI - Combined CT arterial portography and CT hepatic angiography for evaluation of the hepatic resection candidate. Work in progress. AB - PURPOSE: To determine whether the addition of computed tomographic (CT) angiography to CT arterial portography would improve lesion detection and heighten confidence in interpreting perfusion abnormalities. MATERIALS AND METHODS: The two examinations were performed sequentially in 10 candidates for surgical resection of hepatic tumors. Arterial vascular access was obtained with bilateral punctures of the common femoral artery and selective placement of angiographic catheters in the hepatic artery and superior mesenteric artery (SMA). CT scans were obtained first during injection of contrast material into the SMA, followed by repeated imaging of the liver during injection of contrast material into the hepatic artery. RESULTS: The procedure demonstrated, among other results, three additional lesions in two patients, a possibly nontumorous abnormality as tumorous in one, and a suspected tumorous abnormality as nontumorous in one. Suspected nontumorous abnormalities in four patients were confirmed at CT angiography. CONCLUSION: These preliminary data support a trial of this technique in a larger population. PMID- 8210369 TI - Colorectal metastases to the liver: selective chemoembolization. AB - PURPOSE: To evaluate the efficacy and safety of selective chemoembolization in patients with colorectal metastases to the liver. MATERIALS AND METHODS: Forty six patients underwent the regimen, which involved use of doxorubicin and ethiodized oil, with 75% selectively administered to different subsegments and 25% into the respective main hepatic artery. RESULTS: In eight patients, the lesions disappeared and carcinoembryonic antigen levels returned to normal. Eleven patients showed no disease progression for 12 months; two others, for 24 months. Thirteen patients died; three were lost to follow-up in the 1st year. Six patients were followed up for 5 years, seven for 3 years, 16 for 2 years, and 30 for 1 year. Five of seven patients who survived 3 years or more exhibited homogeneous distribution of the chemoembolic agent throughout the metastatic tumor. CONCLUSION: Selective chemoembolization is recommended for treatment of patients with colorectal metastases to the liver, a resectable primary tumor, and no evidence of other metastatic disease. PMID- 8210368 TI - Prospective comparison of T2-weighted fast spin-echo, with and without fat suppression, and conventional spin-echo pulse sequences in the upper abdomen. AB - PURPOSE: To evaluate use of fast spin-echo (FSE) magnetic resonance imaging with and without fat suppression in the liver and upper abdomen. MATERIALS AND METHODS: Conventional spin-echo (SE) T2-weighted, FSE T2-weighted, and fat suppressed FSE T2-weighted images from 37 patients strongly suspected to have focal hepatic lesions were evaluated. RESULTS: Quantitative analysis demonstrated that fat-suppressed FSE imaging had the highest lesion-liver contrast-to-noise ratio; conventional SE imaging, the lowest. In a qualitative analysis, FSE imaging was preferred. In a rank order analysis, FSE imaging was preferred 83% of the time and fat-suppressed FSE imaging 17% of the time as regards overall image quality; fat-suppressed FSE imaging was preferred 64% of the time, FSE imaging 23% of the time, and conventional SE imaging 13% of the time as regards signal abnormality detection. CONCLUSION: FSE imaging with and without fat suppression is a potentially useful pulse sequence for evaluating the upper abdomen. PMID- 8210370 TI - MR cholangiography: clinical evaluation in 40 cases. AB - PURPOSE: To determine the reliability and efficacy of magnetic resonance (MR) cholangiography in demonstrating the site and extent of stricture. MATERIALS AND METHODS: In 40 patients with obstructive jaundice, three-dimensional MR cholangiography was performed with a sequence of mirrored fast imaging with steady-state precession and was compared with conventional cholangiography in 39 cases. The level of obstruction was determined by examining all imaging data available. RESULTS: Diagnostic MR cholangiograms were acquired in 39 patients; absence of obstruction was confirmed in three, and obstruction was seen in 36. The level of obstruction or absence of obstruction was accurately shown in 36 of 40 patients with MR cholangiography and in 37 of 39 patients with conventional cholangiography. The peripheral biliary tree was shown more completely with MR cholangiography than with endoscopic retrograde cholangiography in all 32 patients undergoing diagnostic studies with both modalities. CONCLUSION: Three dimensional MR cholangiography shows particular promise for the assessment of complex strictures, in which conventional cholangiography carries a higher risk of sepsis, for planning optimal drainage before intervention. PMID- 8210372 TI - Laryngeal carcinoma: sclerotic appearance of the cricoid and arytenoid cartilage- CT-pathologic correlation. AB - PURPOSE: To assess the significance of sclerotic-appearing cricoid and arytenoid cartilage with computed tomography (CT) in patients with laryngeal carcinoma. MATERIALS AND METHODS: CT scans obtained in 75 patients with laryngeal carcinoma were prospectively studied; laryngeal CT studies obtained in 50 patients without laryngeal carcinoma were retrospectively reviewed. RESULTS: Twenty-four of the 75 patients (32%) with laryngeal carcinoma had sclerotic cartilage. Evaluation of pathologic specimens obtained in 12 of these 24 patients showed 11 cases of sclerotic arytenoid cartilage and two cases of sclerotic cricoid cartilage. Tumor infiltration was demonstrated in six of these cases but not in the seven others. In 11 of the 12 cases with pathologic proof, however, tumor was adjacent to the perichondrium. In the 12 cases without pathologic proof, the proportion was similar. The positive predictive value of this sign for cartilaginous invasion was 46%. CONCLUSION: Although it is not a reliable sign of cartilaginous invasion, sclerotic-appearing cricoid and arytenoid cartilage in patients with laryngeal carcinoma is predictive of the tumor to this cartilage. PMID- 8210371 TI - Natural history of fundic gland polyposis without familial adenomatosis coli: follow-up observations in 31 patients. AB - PURPOSE: To clarify the natural history of fundic gland polyposis (FGP) without familial adenomatosis coli (FAC). MATERIALS AND METHODS: Thirty-one FGP patients without FAC (six men and 25 women) were followed up with radiography and endoscopy for 1-13 years (mean, 4.3 years). RESULTS: In eight of 11 patients who initially had a single polyp, the polyp disappeared, probably due to endoscopic forceps biopsy. Of 20 patients with multiple polyps, seven (one man and six women with a mean age of 40.6 years at initial diagnosis) had obvious changes in the number of polyps, including complete disappearance in three patients, a decrease in one, transient disappearance followed by recurrence in two, and an increase in one. These patients were younger and had a greater number of polyps at initial diagnosis than the remaining 16 patients without any remarkable change. CONCLUSION: FGP without FAC is characterized by spontaneous decrease or increase in the number of polyps, especially in middle-aged female patients with a large number of polyps. PMID- 8210373 TI - Histopathologic correlates of abnormal water diffusion in cerebral ischemia: diffusion-weighted MR imaging and light and electron microscopic study. AB - PURPOSE: To correlate the findings on diffusion-weighted magnetic resonance (MR) images with the cytologic and histologic findings in ischemic tissue. MATERIALS AND METHODS: A photochemical model of cerebral infarction in rats was studied with diffusion- and T2-weighted MR imaging. The development of lesions was followed from 20 minutes to 5 days after the onset of ischemia. Apparent water diffusion coefficient (ADC) maps were calculated and correlated with light and electron microscopic findings. RESULTS: T2-weighted images clearly showed vasogenic edema but did not enable distinction between areas with cellular damage and the surrounding edematous regions. In contrast, the ADC, which was elevated in nonischemic edematous regions, was diminished in areas with histologic evidence of ischemic damage or necrosis. In the core of the infarct, the ADC became elevated when electron microscopy revealed cellular lysis. CONCLUSION: Diffusion-weighted images may help ascertain the extent of cellular damage and death after stroke. PMID- 8210374 TI - Hypoxic brain damage: cortical laminar necrosis and delayed changes in white matter at sequential MR imaging. AB - PURPOSE: To report the findings of sequential magnetic resonance (MR) imaging in hypoxic encephalopathy. MATERIALS AND METHODS: Three women and three men underwent repeated MR imaging studies. Sequential changes in signal intensity and morphologic features of the brain were evaluated. RESULTS: Involvement of the watershed zones in the parietooccipitotemporal cortex was more frequent and more severe than that in the basal ganglia, thalami, hippocampus, pons, and cerebellum. Cerebral edema was seen in the acute stage. Enhanced T1-weighted images showed cortical laminar enhancement in the early subacute stage; unenhanced T1-weighted images revealed characteristic laminar hyperintense lesions of the cerebral cortex in the late subacute stage. Both of these findings seemed to reflect the progression of cortical laminar necrosis. In the chronic stage, cortical atrophy and delayed but progressive white matter changes were seen. CONCLUSION: Changes in MR imaging features of hypoxic brain damage are complex but distinct. Cortical laminar necrosis, delayed white matter degeneration, and, probably, increased iron deposition in the white matter can be delineated. PMID- 8210376 TI - Brachial plexopathy in infants after traumatic delivery: evaluation with MR imaging. AB - PURPOSE: To determine the value of magnetic resonance (MR) imaging in diagnosing traumatic pseudomeningocele. MATERIAL AND METHODS: Five newborn infants with brachial plexopathy secondary to traumatic delivery underwent MR imaging of the spine and serial neurologic examinations, and the findings were compared. RESULTS: Cervical MR images showed focal collections of cerebrospinal fluid lateral to the spinal cord and extending into the neural foramina. These were believed to represent pseudomeningoceles in four infants, all of whom have persistent major neurologic deficits. The infant with normal cervical MR images has had nearly complete spontaneous recovery. CONCLUSION: Spinal MR images can show pseudomeningoceles, which have been associated with partial or complete nerve root avulsion in infants with birth-related brachial plexopathy. PMID- 8210375 TI - Childhood adrenoleukodystrophy: assessment with proton MR spectroscopy. AB - PURPOSE: Image-guided, single-voxel, localized proton magnetic resonance (MR) spectroscopy was performed to assess white matter in childhood adrenoleukodystrophy (ALD). MATERIALS AND METHODS: Eleven X-linked ALD subjects, seven with neurologic symptoms or white matter lesions at MR imaging and four asymptomatic patients, were compared with nine aged-matched, healthy volunteers. RESULTS: Compared with those from normal white matter, MR spectra from white matter lesions (n = 6) showed 65% reduction in the ratio of N-acetyl aspartate (NAA) to total creatine (tCr) (P < .01); 55% increase in the ratio of choline containing compounds (Cho) to tCr (P < .02); substantial levels of tCr; 94% increase in the ratio of glutamate, glutamine, or inositol to tCr (P < .02); and lactate accumulation in four patients. Patients without brain lesions (n = 4) exhibited a 51% increase in Cho-to-tCr ratio (P < .01) and 11% nonsignificant increase in NAA-to-tCr ratio. CONCLUSION: Proton MR spectroscopy may prove a valuable technique for noninvasive diagnostic and prognostic assessment of ALD. PMID- 8210377 TI - Hip aspiration: a cost-effective and accurate method of evaluating the potentially infected hip prosthesis. AB - PURPOSE: The accuracy of fluoroscopy-guided hip aspiration in the diagnosis of infection in hip prostheses was evaluated. MATERIALS AND METHODS: Results from 147 preoperative aspiration cultures were compared with results of operative cultures. The relative costs of aspiration and nuclear medicine studies were also compared. RESULTS: With the operative culture results as the standard, sensitivity of hip aspiration was 92.8% and specificity was 91.7%. The negative and positive predictive values were 99.2% and 54.2%, respectively. Aspiration arthrography costs approximately 20% as much as complementary technetium sulfur colloid-indium-111 granulocyte scans, the most accurate nuclear medicine study used to evaluate potentially infected hip prostheses. CONCLUSION: Hip aspiration is an accurate and cost-effective method of evaluating the potentially infected hip prosthesis. PMID- 8210378 TI - Spinal tuberculosis: atypical observations at MR imaging. AB - PURPOSE: To evaluate atypical magnetic resonance (MR) imaging features of spinal tuberculosis. MATERIALS AND METHODS: Between 1990 and 1993, five of 11 consecutive patients with spinal tuberculosis (two men and three women, aged 30 57 years) had MR findings more suggestive of neoplasm than infection. One patient, a European immigrant, had acquired immunodeficiency syndrome (AIDS). RESULTS: Areas involved with tuberculosis were hypointense on T1-weighted images and hyperintense on T2-weighted images, and became enhanced with gadopentetate dimeglumine. In two patients, tuberculosis affected only a single vertebral body without paraspinal abscesses or involvement of the end plates and disk spaces. In two other patients, only a single spinous process was replaced with tuberculous abscess. In the remaining patient, the sacrum and multiple lower lumbar vertebrae were affected, but the intervertebral disk spaces were not affected. More typical findings of spinal tuberculosis include destruction of two adjacent vertebral bodies and opposing end plates, destruction of intervening disk space, and/or occurrence of paravertebral abscesses. CONCLUSION: Neither clinical examination nor MR findings may be reliable in helping differentiate spinal infections from one another or from neoplasm. Adequate biopsy is essential for early diagnosis and prompt treatment. PMID- 8210379 TI - Calcification demonstrated as high signal intensity on T1-weighted MR images of the disks of the lumbar spine. AB - PURPOSE: To report that calcification of lumbar disks may not show the usual low signal intensity on T1-weighted magnetic resonance (MR) images. MATERIALS AND METHODS: The authors present five cases of high signal intensity on T1-weighted MR images of a lumbar disk that reflect the presence of calcium deposition. RESULTS: In four cases there was conventional radiographic confirmation and in one case there was computed tomographic confirmation of the disk calcification, which corresponded to the high signal intensity seen on the MR studies. One patient had undergone surgical removal of a partially calcified protruding disk. CONCLUSION: Lumbar disk calcification can vary in signal intensity from low to high on T1-weighted MR images. PMID- 8210380 TI - Relationship of osteophytes to bone mineral density and spinal fracture in men. AB - PURPOSE: To investigate the relationship of spinal osteophytes to vertebral bone mineral density (BMD) and to spinal fracture. MATERIALS AND METHODS: This relationship was investigated in 203 men. Integral BMD was measured with dual x ray absorptiometry, and both cortical and trabecular BMD were measured with quantitative computed tomography (QCT). RESULTS: Trabecular BMD was found to decrease with age in subjects with and without large osteophytes, while cortical and integral BMD decreased with age only in subjects without large osteophytes. Trabecular BMD in men without fracture was significantly higher than in those with fracture (P < .05 for BMD measured with single-energy QCT), while there was no significant difference between these groups in cortical or integral BMD. CONCLUSION: Measurement of trabecular BMD with QCT provides information useful in detection of age-related bone loss and of fracture in men with and without osteophytes. PMID- 8210381 TI - Diagnosis of low-grade chondrosarcoma. PMID- 8210382 TI - Plasma cell tumors with calcified amyloid deposition mistaken for chondrosarcoma. AB - PURPOSE: To report cases of plasmacytoma with a radiologic appearance simulating that of chondrosarcoma. MATERIALS AND METHODS: The authors describe four cases of plasma cell tumors with scattered foci of calcification within their matrix, causing them to resemble chondrosarcoma radiographically. Histologic examination was performed in three of these cases. RESULTS: Biopsy specimens demonstrated that the calcification in these tumors was contained in areas of amyloid deposition. Although amyloid formation in association with plasma cell dyscrasias is well known, sufficient calcification within the amyloid to become radiographically identifiable has only rarely been reported. CONCLUSION: Calcification in amyloid produced by plasma cell tumors may at times simulate the appearance of chondrosarcoma. PMID- 8210383 TI - Denervated skeletal muscle: MR imaging. Work in progress. AB - PURPOSE: To evaluate the change in signal intensity of skeletal muscles after denervation and to determine the clinical usefulness of magnetic resonance (MR) imaging in diagnosis of denervation. MATERIALS AND METHODS: Denervated skeletal muscles associated with various forms of peripheral neuropathy and spinal radiculopathy were studied with MR imaging in 17 patients. RESULTS: On T1 weighted images, signal intensity of denervated muscles was normal in 14 patients and high in three. On T2-weighted images, all denervated muscles showed high signal intensity on at least one MR image. High signal intensity in the denervated muscles on T2-weighted images was observed 15 or more days after onset of paralysis. In two patients, signal intensity of denervated muscles returned to normal after relief of paralysis. CONCLUSION: MR imaging is a noninvasive and accurate method for use in diagnosis of denervation and may ultimately eliminate the need for electromyography. PMID- 8210384 TI - Cardiac abnormalities: assessment with T2-weighted turbo spin-echo MR imaging with electrocardiogram gating at 0.5 T. AB - PURPOSE: To evaluate the cardiovascular system with magnetic resonance (MR) imaging performed with the turbo spin-echo (TSE) method and electrocardiogram (ECG) gating. MATERIALS AND METHODS: ECG-gated T2-weighted TSE images were obtained in 52 patients with 68 pathologic conditions (intracardiac [n = 18], myocardial [n = 23], pericardial [n = 6], paracardial [n = 10], or aortic [n = 11] disease) and 10 healthy subjects. In healthy subjects, TSE parameters were tested and optimized, and signal-to-noise ratios (S/Ns) and contrast-to-noise ratios (C/Ns) were determined. Delineation of the endo-, epi-, and pericardial borders and signal intensity characteristics of myocardium, fat, pericardium, blood flow, tumors, and clots were assessed. RESULTS: The TSE method provided good-quality T2-weighted images with sharp edge definition in a short imaging time. Increasing the turbo factor reduced motion artifacts and preserved the S/N and C/N. TSE images also helped in diagnosis of tumors, pleural effusions, inflammatory changes, and intravascular clots. CONCLUSION: TSE MR imaging is a feasible alternative to time-consuming conventional SE MR imaging, reduces motion artifact, and may help in evaluation of the cardiovascular system. PMID- 8210385 TI - Pulmonary angiography with MR imaging: preliminary clinical experience. AB - PURPOSE: To study the accuracy of magnetic resonance (MR) pulmonary angiography in 20 patients in whom pulmonary embolism (PE) was clinically suspected. MATERIALS AND METHODS: Fourteen patients (group 1) were recruited for the MR pulmonary angiography study before they underwent conventional pulmonary angiography (CPA) based on clinical findings. Six patients (group 2) did not undergo CPA but were considered to have PE on the basis of findings in other studies. MR venography was performed at the time of MR pulmonary angiography in 13 patients. RESULTS: MR pulmonary angiography had a sensitivity of 92%-100% and specificity of 62% for detection of PE. Performance of MR pulmonary arteriography and MR venography in a single examination to demonstrate thrombus in both the arterial and deep venous systems was proved feasible. CONCLUSION: This report describes an early clinical implementation of new MR pulmonary angiographic techniques. Further advances to improve specificity by enhancing sensitivity to slow flow and increasing spatial resolution are necessary before routine clinical use of MR pulmonary angiography is justified. PMID- 8210386 TI - Self-expandable metallic stent therapy for superior vena cava syndrome: clinical observations. AB - PURPOSE: To study clinical and physiologic aspects of Z-stent therapy for superior vena cava (SVC) syndrome secondary to malignant disease. MATERIALS AND METHODS: Signs and symptoms of SVC syndrome were classified, graded, and scored in 11 cases. Six patients with caval pressure higher than 22 mm Hg peripheral to the stenosis underwent stent therapy. RESULTS: Immediately after Z-stent implantation into the stenotic lesion, the diameter of the constriction increased from 3.3 mm +/- 2.0 (mean +/- standard deviation) to 14.0 mm +/- 3.2, the mean caval pressure peripheral to the stenosis decreased from 26.6 mm Hg +/- 2.5 to 8.9 mm Hg +/- 0.7, and the symptom score decreased from 6.7 +/- 1.8 to 1.3 +/- 1.4. The caval pressure, lesion diameter, and symptom score correlated highly with each other. One complication--transient pulmonary edema attributable to volume overload caused by reperfusion--was observed. Mean survival exceeded 7.1 months. CONCLUSION: Stent placement could be a useful treatment for refractory SVC syndrome. PMID- 8210387 TI - Percutaneous recanalization of iliac artery occlusions: results of a prospective study. AB - PURPOSE: To evaluate the long-term results of recanalization of occluded iliac arteries with local low-dose thrombolysis, angioplasty, and, if necessary, stent implantation. MATERIALS AND METHODS: Forty-seven patients with acute or chronic occlusions of the common or external iliac artery, or both, underwent local low dose thrombolysis (n = 47), percutaneous transluminal angioplasty (PTA) (with balloon dilation [n = 43] and rotational angioplasty [n = 30] in the patients in whom a retrograde recanalization was performed), and, if needed, intravascular stent placement (n = 18). Follow-up lasted 3-53 (mean, 21) months. RESULTS: The primary recanalization rate was 98% (46 of 47). The mean ankle-brachial index increased from 0.33 to 0.81 within 14 days after treatment and was 0.76 at the most recent follow-up. Two early (< 14 days) and two late reocclusions (after 24 and 30 months) occurred; one restenosis detected with duplex sonography and angiography was observed after 19 months. CONCLUSION: This therapy represents a true alternative to vascular surgery and a first-line treatment for acute or chronically occluded iliac arteries. PMID- 8210388 TI - Effect of local low-dose thrombolysis on clinical outcome in acute embolic renal artery occlusion. AB - PURPOSE: To determine the utility of local thrombolysis in treatment of acute embolic renal artery occlusion. MATERIALS AND METHODS: Fourteen patients with acute embolic renal artery occlusion treated with local low-dose thrombolysis were studied. Diagnosis was made with renal scintigraphy and selective renal arteriography. RESULTS: Thrombolysis was successful in 13 of 14 patients. During 1-72 months of follow-up (mean, 27.1 months), renal function did not improve on the side of complete renal artery occlusion, whereas stabilization of renal function at the pretherapy level was seen in patients with incomplete obstruction of the renal artery or complete obstruction at the level of segmental branches. In none of the patients did renal function return to normal. CONCLUSION: In acute embolic renal artery occlusion, thrombolytic therapy does not restore renal function and is therefore not indicated once the ischemic tolerance of the kidney (approximately 90 minutes) has been exceeded. PMID- 8210389 TI - Acute pulmonary embolism: artificial neural network approach for diagnosis. AB - PURPOSE: To investigate use of an artificial neural network (ANN) as a computer aided diagnostic (CAD) tool for predicting pulmonary embolism (PE) from ventilation-perfusion lung scans and chest radiographs. MATERIALS AND METHODS: The data base consisted of cases extracted from the collaborative study of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). Initially, scan findings from 1,064 patients (383 with PE, 681 without PE) were used to train and test the network by using the "jackknife" method. Then, a receiver operating-characteristic analysis was applied to compare the performance of the network with that of the physicians involved in the PIOPED study. RESULTS: The ANN significantly outperformed the physicians involved in the PIOPED study (two tailed P value = .01). CONCLUSION: The findings suggest that an ANN can form the basis of a CAD system to assist physicians with the diagnosis of PE. PMID- 8210390 TI - Diffuse panbronchiolitis: follow-up CT examination. AB - PURPOSE: The authors reviewed serial computed tomographic (CT) scans obtained in 19 patients with diffuse panbronchiolitis (DPB) to evaluate changes in disease pattern over time. MATERIALS AND METHODS: Nineteen patients with DPB were entered into the study. After initial CT examination, 12 patients were randomly assigned to receive long-term low-dose (200 mg three times daily) erythromycin therapy; seven patients received no treatment. RESULTS: Follow-up CT scans revealed that centrilobular areas of high attenuation observed initially had progressed to dilatation of the proximal airway in some patients in the untreated group. In the treated group, the centrilobular and branched linear areas of high attenuation were decreased in number and size, although the airway dilatation and decreased lung attenuation in the peripheral areas remained unchanged or were slightly increased. CONCLUSION: CT scans are valuable in the study of the disease process and response to therapy in DPB. PMID- 8210391 TI - Accessory cardiac bronchus: CT features and clinical significance. AB - PURPOSE: The accessory cardiac bronchus is a rare congenital anomaly of the tracheobronchial tree that arises from the medial wall of the bronchus intermedius. This report documents the computed tomographic (CT) appearance of this anomaly. MATERIALS AND METHODS: Six patients with this anomaly were identified. All six underwent CT; three underwent correlative bronchoscopy, and one had both bronchoscopic and surgical confirmation. RESULTS: In all six cases, a distinct airway could be identified originating from the medial wall of the bronchus intermedius. Associated lung parenchymal tissue was identified in four cases, while in three cases a discrete soft-tissue mass was seen, presumably representing vascularized bronchial or vestigial parenchymal tissue. In two cases, the lumen of the airway was filled with debris. CONCLUSION: Recognition of this anomaly is important, as associated clinical complications, including recurrent episodes of both infection and hemoptysis, may be anticipated in a small percentage of patients. PMID- 8210392 TI - Solid breast lesions: diagnosis with US-guided fine-needle aspiration biopsy. AB - PURPOSE: To ascertain the usefulness of real-time ultrasound (US)-guided fine needle aspiration biopsy as an adjunct to clinical, mammographic, and sonographic assessment of solid breast lesions. MATERIALS AND METHODS: US-guided fine-needle aspiration biopsy was performed in 225 malignant and 580 benign solid breast lesions confirmed by means of excisional biopsy or with imaging follow-up (mammography or US) performed at approximate intervals of 6, 12, 24, and 36 months. All lesions were classified as palpable or nonpalpable at clinical examination and visible or nonvisible on mammograms. RESULTS: In 213 malignant lesions (95%), the cytologic findings were malignant or suspicious, with no false positive and 12 false-negative cases. Mammography did not enable detection of 58 cancers (26%), 43 of which were palpable. Fifteen cancers discovered with US were nonpalpable and not seen on mammograms. Cytologic diagnosis of fibroadenoma or nonspecific benign cells was correct in 535 lesions. The sensitivity of this method was 95%; specificity, 92%; and overall accuracy, 93%. CONCLUSION: Real time US-guided fine-needle aspiration biopsy is a useful adjunct to clinical, mammographic, and sonographic assessment of solid breast lesions. PMID- 8210393 TI - Effects of ionizing radiation and magnetic fields on digital data stored on floppy disks. AB - PURPOSE: To evaluate the effect of x rays and magnetic fields on high-density, 3.5-inch floppy disks. MATERIALS AND METHODS: A 1-Mbyte worksheet file was stored on 20 recently purchased high-density floppy disks. Five disks were stored as controls. Five other disks were then exposed to 70-kVp and 6-MV x rays with exposures of 100-1,000 R (0.026-0.26 C.kg-1). Ten other disks were exposed to magnetic fields with a maximum strength of 1,000 G. Magnetic fields around an airport metal detector and x-ray unit were measured. Another set of 10 disks was passed through the metal detector 50 times and through the x-ray unit 12 times. RESULTS: Ionizing radiation had no effect on the data stored on the disks. Magnetic fields with a maximum strength of 500 G had no effect, but field strengths of 1,000 G completely erased the data. Neither the airport metal detector nor the x-ray unit had any effect on the data. CONCLUSION: Airport metal detectors and x-ray scanners have no effect on digital data stored on floppy disks. PMID- 8210394 TI - MR procedures and biomedical implants, materials, and devices: 1993 update. AB - PURPOSE: To provide information on ferromagnetic metallic implants, materials, and devices that may be exposed to static magnetic fields during magnetic resonance (MR) imaging or spectroscopy. MATERIALS AND METHODS: An updated compilation of the results of more than 80 studies lists the specific object tested, the material used to construct the object, whether the object was deflected or moved during exposure to the static magnetic field, and the highest field strength used for testing the object (range, 0.147-4.7 T). RESULTS: The ferromagnetic qualities of 338 objects (32 aneurysm and hemostatic clips; six biopsy needles; five carotid artery vascular clamps; 18 dental devices or materials; 11 halo vests; 29 heart valve prostheses; 20 intravascular coils, filters, and stents; 22 ocular implants; 30 orthopedic implants, materials, and devices; 62 otologic implants; 23 pellets and bullets; 13 penile implants; 38 vascular access ports; and 29 miscellaneous objects) are reported. CONCLUSION: MR imaging or spectroscopy may be contraindicated in patients with such objects because of the risk of movement or dislodgment of the object. PMID- 8210396 TI - Isolated vaginal recurrences of endometrial carcinoma. AB - PURPOSE: The authors undertook this study to evaluate the results of radiation therapy (RT) for vaginal recurrence in early stage endometrial carcinoma. MATERIALS AND METHODS: Between 1964 and 1987, 34 patients with isolated vaginal recurrences of endometrial carcinoma were treated with RT. The records were reviewed for outcome and prognostic factors, such as location of tumor recurrence, time to recurrence, size of tumor at recurrence, tumor differentiation, and total radiation dose delivered at RT. RESULTS: With a median follow-up of 48 months, the 5-year actuarial survival and disease-free survival rates were 68% +/- 4 and 60% +/- 3, respectively. Results were statistically significant for some prognostic factors, including time to tumor recurrence and total radiation dose delivered at RT to the recurring tumor. CONCLUSION: Long term survival can be obtained for patients with an isolated vaginal recurrence of endometrial cancer treated with aggressive local-regional radiation therapy. PMID- 8210395 TI - Cervical cancer: application of MR imaging in radiation therapy. AB - PURPOSE: To evaluate magnetic resonance (MR) imaging in the planning of radiation therapy for patients with cervical cancer. MATERIALS AND METHODS: MR imaging was performed in 15 patients with predominantly advanced cervical carcinomas. Skin markings of the radiation ports were labeled with MR-detectable tubing and beads to assess the adequacy of port placement. Volume and extent of tumor at MR imaging were compared with those at physical and computed tomographic (CT) examinations. RESULTS: Tumor involvement of normal structures (parametrium, vagina, endometrium) was more extensive at MR imaging than at clinical examination in six patients (40%) and at CT in five patients (33%), resulting in modification of the radiation fields in eight patients (53%). Tumor size was larger on MR images than at clinical examination in 11 patients (73%). CONCLUSION: MR imaging can depict tumor volume and better delineate the extent of involvement than physical and CT examination. This can be useful for placement of radiation ports, especially when small boost fields are used. PMID- 8210397 TI - Modification of a syringe for aspiration biopsy. AB - To reduce the risk of accidental needle-stick injury during fine-needle aspiration biopsy, a syringe to be used in such procedures was modified. In five cases, a small hole, punctured in the barrel of a syringe above the level to which the plunger is routinely retracted, allowed the syringe to fill with air. The specimen was expressed onto a slide without the necessity of removing and reattaching the needle. This modification reduces the need to handle contaminated needles. PMID- 8210398 TI - Percutaneous biopsy of osteolytic lesions: use of a biopsy gun. AB - Percutaneous bone biopsy with use of traditional trephine needles may be unsuccessful in osteolytic lesions. The authors used an 18-gauge biopsy gun in 25 consecutive lytic lesions. This procedure was safe, effective, and not technically difficult. Use of biopsy guns with detachable handles made positioning with computed tomography (CT) guidance less difficult. The only technical difficulty arose in biopsy of small lesions, in which the gun may misfire when contacting solid bone. A biopsy gun is an effective tool in the biopsy of osteolytic lesions. PMID- 8210399 TI - Differentiation of silicone gel from water and fat in MR phase imaging of protons at 0.064 T. AB - The authors present a method of identifying silicone at magnetic resonance (MR) imaging based on its chemical shift. The method relies on phase images reconstructed from a gradient-recalled-echo sequence that has an echo time chosen to maximize the phase offsets between water, fat, and silicone. Results from studies at 0.064 T of both phantoms and human subjects are presented. This technique was useful in identifying extracapsular silicone and may be applicable at other field strengths. PMID- 8210400 TI - Occluded coloanal anastomosis: transrectal US-guided balloon dilation. AB - Balloon dilation is a well-described, nonoperative, alternative treatment for postoperative strictures of the colon and rectum. This procedure may not be technically feasible when an occluded lumen prevents passage of a guide wire across the obstruction. The authors describe the use of transrectal ultrasound guidance to initially pass a needle across an occlusive web at the coloanal anastomosis after proctosigmoidectomy. This allowed placement of a guide wire across the occlusion and subsequent successful balloon dilation. PMID- 8210401 TI - Preoperative needle localization in the breast: utility of local anesthesia. PMID- 8210402 TI - Was heparin the culprit? PMID- 8210403 TI - 79th Scientific Assembly and Annual Meeting of the Radiological Society of North America. Program and Abstracts. PMID- 8210404 TI - DNR order ignored: "wrongful life" suit. PMID- 8210405 TI - Legal case briefs for nurses. MT: hospice nurses stash morphine for pts.: Board's disciplinary action voided; TS: one day's atypical behavior by R.N.: Board's licence revocation voided. PMID- 8210406 TI - Failure to follow orders: patient arrests--coma results. Case in point: Sullivan v. Sumrall By Ritchley 618 So. 2d 1274--MS (1993). PMID- 8210407 TI - [Effect of the vegetative cover on the biological activity of the soil of Chaco Arido]. AB - Vegetation plays a primal role in arid ecosystems, since it creates microclimate conditions that moderate the characteristics of the region whereby the rational use of vegetal resources is fundamental. Felling, clearing and overgrazing lead to decrease in organic contribution and stimulate soil compaction, causing an alteration of microbial activity, with losses in nutrient turnover. The global biological activity is a soil parameter easy to obtain and indicates the presence and diversity of soil life as well as substrate availability and is useful in order to characterize soil potential fertility. This work was carried out in Natural Forest Reserve Chancani, Province of Cordoba (Argentina), which is representative of Argentine Dry Chaco. Dominant tree species are: Prosopis flexuosa and Aspidosperma quebracho blanco. The global biological activity (GBA) was measured along one year, under trees, under shrubs and in interspaces. Soil samples were taken monthly from plots with four management systems: 1) forest, ii) selective clearing (only dominant species remain), iii) bush (clearing invaded by Larrea sp) and iv) grazing (cleared area, neither trees nor shrubs). GBA was evaluated using the CO2 release method, after ten days of incubation. It is concluded that in the plots with grasses and under the trees GBA was higher than with other treatments. The lesser GBA was detected in bushes and interspaces. All differences were more prominent during extreme temperature months. No significant difference between both species of dominant trees was observed. PMID- 8210408 TI - [Diagnosis of entero-invasive Escherichia coli associated with diarrhea]. AB - Sixteen Escherichia coli strains isolated from diarrhea patients, characterized as enteroinvasive (EIEC) by the keratoconjunctivitis test (Sereny test), and 15 non-EIEC strains, were studied. The aim of this study was to establish a possible correlation between the Sereny test and several other tests as enzyme-linked immunosorbent assay (ELISA) and biochemical markers, which are more easily accessible to general practice laboratories. Strains were assayed for the virulence marker antigen (the outer membrane proteins) by direct ELISA, biochemical tests, antimicrobial susceptibility profile and serotyping. Mean optical density (OD) values in the ELISA were 2.018 +/- 0.336 for EIEC strains, and 0.569 +/- 0.283 for non-EIEC strains. Difference between the OD values of the two groups was found to be significant at p < 0.01 by the one-tailed Student's test. One (6.2%) of the 16 Sereny test-positive strains was negative by ELISA. Considered as a group, the EIEC strains are rather heterogeneous in their biochemical characteristics. Lysine decarboxylase test appeared as the most relevant assay, since all EIEC strains were negative for this enzyme, whereas 66.7% of non-EIEC strains were positive. Other helpful tests performed for strain characterization were: gas production from glucose and from glycerol, sucrose and salicin fermentation, and esculin hydrolysis (p < 0.01). However, strains behaviour was variable with these tests. Differences between both groups of strains with regard to mucate utilization and dulcitol fermentation was significative only to a 5% level. Antibiotic sensitivity patterns showed differences between EIEC and non-EIEC strains: 37.5% of the former vs 80% of the latter, were resistant to at least four of the antibiotics tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210409 TI - [Isolation of antibiotic-resistant Escherichia coli from the water of the Rio de la Plata]. AB - Water of a recreational zone of the Rio de la Plata was analyzed. Levels of total heterotrophic bacteria ranged from 1.5 x 10(3) to 6.2 x 10(3) CFU/ml and total coliforms were between 5.0 x 10(2) and 7.0 x 10(3) per 100 ml. Values of fecal coliforms were between 1.0 x 10(2) and 1.3 x 10(3) per 100 ml. Among 131 E. coli strains isolated, 20.6% of cephalothin resistance was found, followed by nitrofurantoin, ampicillin, sulfisoxazole and the trimethoprim sulfamethoxazole combination. Resistance to more than one antibiotic was found in 36.7% of the strains isolated and 9.2% were resistant to three or more antibiotics. Three strains resistant to four antibiotics and one resistant to five were isolated. The highest percentage of combined resistance occurred for the pairs cephalothin nitrofurantoin and cephalothin-ampicillin. PMID- 8210410 TI - Plasticity of the dendritic spine. PMID- 8210411 TI - Audition and the auditory pathway of a vocal New World primate, the common marmoset. PMID- 8210412 TI - EEG and event-related potentials in normal aging. PMID- 8210413 TI - Visual-vestibular interaction in the control of head and eye movement: the role of visual feedback and predictive mechanisms. PMID- 8210414 TI - The toad, ugly and venomous, wears yet a precious jewel in his skin. PMID- 8210415 TI - [Morphological abnormalities of eukaryotic cells induced by microbial metabolites as indices to detect nobel physiological activities]. PMID- 8210416 TI - [A system of classifying inhibitors of cellular functions by target molecules using echinoderm gametes and embryos]. PMID- 8210417 TI - [Immunomodulators in microbial metabolites]. PMID- 8210418 TI - [Bone formation and BMPs]. PMID- 8210419 TI - [Modulators of oncogene product functions]. PMID- 8210420 TI - [Inhibitors of intracellular translocation of glycoproteins]. PMID- 8210421 TI - [Modifiers of calcium action]. PMID- 8210422 TI - [Inhibitors of tubulin assembly: specially on rhizoxin-maytansine site ligands]. PMID- 8210423 TI - [Inhibitors of cell cycle progression and its regulation]. PMID- 8210425 TI - [Antioxidative agents produced by microorganisms]. PMID- 8210424 TI - [Antioxidants from plants]. PMID- 8210426 TI - [Differentiation inducing compounds]. PMID- 8210427 TI - [Receptor agonists and antagonists: the present and future]. PMID- 8210428 TI - [Agonists and antagonists to endothelin receptors]. PMID- 8210430 TI - [NMDA agonists and antagonists]. PMID- 8210429 TI - [Cholecystokinin receptor antagonists]. PMID- 8210431 TI - [Nonpeptide angiotensin II receptor antagonists]. PMID- 8210432 TI - [Motilide, motilin-like macrolides]. PMID- 8210433 TI - [An outline of enzyme inhibitors]. PMID- 8210434 TI - [HMG-CoA reductase inhibitor, pravastatin]. PMID- 8210435 TI - [Triacsins, inhibitors of fatty acid activating enzyme]. PMID- 8210436 TI - [Protein tyrosine kinase inhibitor, herbimycin A]. PMID- 8210437 TI - [Inhibitors of protein phosphatases]. PMID- 8210438 TI - [Prolyl endopeptidase inhibitors]. PMID- 8210439 TI - [Phospholipase A2 inhibitors]. PMID- 8210440 TI - [Bafilomycins and related compounds as vacuolar H(+)-ATPase inhibitors]. PMID- 8210441 TI - [HIV protease inhibitors]. PMID- 8210442 TI - Prostaglandin E2, cAMP and cAMP-dependent protein kinase isozymes during decidualization of rat endometrial stromal cells in vitro. AB - When endometrial stromal cells from rat uteri sensitized for the decidual cell reaction are cultured in vitro, they undergo decidualization, as indicated by increased alkaline phosphatase (ALP) activity. Prostaglandin E2 (PGE2) stimulates this increase in activity. To determine the role of cAMP in the stimulation, we examined the effect of 2':5'-dideoxyadenosine (DDA), an inhibitor of adenylate cyclase, on the ability of PGE2 to increase ALP activity. As indicated by [3H]cAMP accumulation in endometrial stromal cells preincubated with [3H]adenine, DDA inhibited PGE2-stimulated synthesis of cAMP in a concentration-dependent manner. Furthermore, DDA caused a significant decrease in the PGE2-induced ALP activity on day 3 of culture. Dibutyryl cAMP overrode this inhibition. The effect of DDA was not mimicked by adenosine, which had a stimulatory effect on ALP activity in the non-stimulated cultures and no significant effect in PGE2 stimulated cultures. Thus the inhibitory effect of DDA on PGE2-stimulated ALP activity is unlikely to be mediated by adenosine-related receptors. These results suggest that cAMP is an essential, but not necessarily the only, intracellular messenger of PGE2 in endometrial stromal cells during decidualization. The isozymes of cAMP-dependent protein kinase (PKA) mediating the effect of cAMP were assessed by using cAMP analogues directed at selective sites of PKA isozymes. Synergistic activation of ALP activity in endometrial stromal cells by pairs of analogues directed at types I and II PKA suggested that both types were functionally important during decidualization. PMID- 8210443 TI - Differential induction of c-jun expression by PGF2-alpha in rat ovary, uterus and adrenal. AB - The influence of PGF2 alpha on c-jun gene expression in ovary, uterus and adrenal was examined. Three and seven day postovulatory PMSG primed immature rats received 500 ug PGF2 alpha by two subcutaneous injections 8 hours apart. Control rats received saline. Animals were sacrificed 30 minutes after the second injection of PGF2 alpha. Tissues were obtained and frozen in liquid nitrogen. RNA extracted from ovary, uterus and adrenal was analyzed by Northern and slot blot. c-jun was expressed differentially in these organs. An increase in c-jun expression by PGF2 alpha treatment occurred in the ovary but not in the adrenal and uterus. The effect of PGF2 alpha on c-jun was stronger in older compared to younger corpora lutea. These results indicate differential regulation of c-jun by PGF2 alpha in steroidogenic and steroid responsive tissues and that c-jun might be linked to the mode of action of PGF2 alpha in luteolysis. PMID- 8210444 TI - Actions of interleukin-2 on chorio-decidual prostaglandin biosynthesis. AB - The onset of preterm labor requires increased intrauterine prostaglandin production. Intrauterine infections are frequently associated with preterm labor and increased cytokine production. The cytokine interleukin-2 (IL-2) is a potent T-cell growth factor necessary for effective cell-mediated immunity. In this study we evaluated the effect IL-2 has on prostaglandin E2 (PGE2) biosynthesis by human chorion and decidual cells. IL-2 alone significantly stimulated decidual and chorion PGE2 production. IL-2 enhanced the stimulatory actions of interleukin 1 (IL-1), epidermal growth factor (EGF), ionomycin, and phorbol 12-myristate 13 acetate (PMA) on PGE2 production by decidual cells. Similarly, IL-2 enhanced the stimulatory actions of EGF and PMA, but not IL-1 or ionomycin, on PGE2 production by chorion cells. These data suggest that IL-2 could potentially participate in the mechanisms of preterm labor in association with intrauterine infection. PMID- 8210445 TI - Effect of 13-hydroperoxyoctadecadienoic acid on 15-hydroxy prostaglandin dehydrogenase activity in rabbit kidney cortex. AB - The effect of a hydroperoxy adduct of linoleic acid, 13 hydroperoxyoctadecadienoic acid (13-HPODE), on 15-hydroxy prostaglandin dehydrogenase activity in rabbit kidney cortex was examined. 13-HPODE inhibited the 15-hydroxy prostaglandin dehydrogenase activity at concentrations ranging from 1 to 10 microM. The effect was concentration-dependent and the concentration required for 50% inhibition was approximately 3 microM. Linoleic acid and 13 hydroxyoctadecadienoic acid (13-HODE) exhibited weaker inhibition of the enzyme activity than did 13-HPODE (linoleic acid, 30% inhibition at 10 microM; 13-HODE, 45% inhibition at 10 microM). Studies utilizing Fe2+ (a catalyst of peroxide decomposition), and mannitol or dimethylsulfoxide (a hydroxy radical scavenger) revealed that the inhibitory effect of 13-HPODE on the 15-hydroxy prostaglandin dehydrogenase activity is not due to the hydroxy radicals which are expected to be formed from 13-HPODE and that the hydroperoxy functional group is a prerequisite. The inhibition by 13-HPODE was uncompetitive and non-competitive with regard to NAD+ and prostaglandin E2, respectively. These results suggest that 13-HPODE has the potential to modulate the prostaglandin catabolism by affecting the 15-hydroxy prostaglandin dehydrogenase activity. PMID- 8210446 TI - Urinary excretion of 6-keto-PGF1 alpha TxB2 and PGE2 in a rat animal model for preeclampsia-like syndrome. AB - The etiology of pregnancy induced hypertension (PIH) is still unknown. The pathophysiology must be clarified. In this paper we present an animal model where hypertension in pregnant and non-pregnant rats was induced by an experimental reduction of uteroplacental blood flow. Thus, a preeclampsia-like syndrome could be studied under defined conditions. The eicosanoid system was investigated for pathophysiological alterations of the kidney by measuring urinary excretion of 6 keto-PGF1 alpha, TxB2 and PGE2 with radioimmunoassay at day 18 of pregnancy. First, in gravid control animals concentrations of all three prostaglandins were significantly elevated compared to non-gravid controls. However, in hypertensive gravid rats urinary concentrations of these prostaglandins fell even below the levels of non-gravid controls. The observed decrease was more pronounced for the vasodilatory 6-keto-PGF1 alpha and PGE2 than for the vasoconstrictive TxB2. Our results demonstrate that an experimental reduction of uteroplacental blood flow in the rat culminates in symptoms which clinically (hypertension, proteinuria) and pathophysiologically (eicosanoid system) resemble to preeclampsia. PMID- 8210447 TI - A review--role of eicosanoids in vertebrate ovulation. PMID- 8210448 TI - [The patient as manifestation and narrative: disease pictures, life stories and the first psychoanalytic case report]. PMID- 8210449 TI - [Remarks on false interpretations of Freud's seduction theory]. PMID- 8210450 TI - [On the way to the secret of Freudian psychoanalysis. From Emmy von N. to "Totem and taboo"]. AB - The authors approach the work of Sigmund Freud by regarding the theory and history of psychoanalysis in terms of a feature that they have in common, namely secrecy. This proclivity towards secrecy, which stands in contradiction to the psychoanalytic principle of total frankness and demystification, is illustrated by a number of examples-the suggestion made by Jones to Ferenczi and Freud in 1911 for the "formation of a secret committee to supervise the development of psychoanalysis"; the censorship practised by Jones in connection with the use of the Freud Archives; and the case history of Emmy von N., where Freud assumes the role of depositary for the memories communicated by his patient under hypnosis and observes strict secrecy about them. The authors give a particularly detailed account of the evidence of the "secret of psychoanalysis" to be traced in Totem and Taboo, which they elucidate with the aid of a reading of Shakespeare's Tempest. PMID- 8210451 TI - [The Olympic Games of psychotherapy: research evaluation of psychotherapy regulations]. PMID- 8210452 TI - Effects of exposure to a to-be-shocked environment upon the rat's freezing response: evidence for facilitation, latent inhibition, and perceptual learning. AB - Three experiments used the freezing response of rats to examine the effects of pre-exposure to an environment upon (1) its associability with shock and (2) its discriminability from a second environment. Experiments 1 and 2 demonstrated that freezing was proportional to the interval between exposure to the environment at time T1 and the occurrence of shock at T2. This function was shifted by pre exposure to the to-be-shocked environment, with brief pre-exposures increasing (facilitation) and extended pre-exposures decreasing (latent inhibition) the impact of a given T1-T2 interval on freezing. Experiment 3 provided evidence that the facilitatory and latent inhibitory effects resulting from brief and extended exposures to the to-be-shocked environment were accompanied by an increase in discriminability. The results were taken to have supported the claim that pre exposure changes associability as well as discriminability (Hall & Honey, 1989) and were discussed in terms of the model for perceptual learning proposed by McLaren, Kaye, and Mackintosh (1990). PMID- 8210453 TI - The effect of intertrial food presentations on anticipatory goal-tracking in the rat. AB - Four experiments examined the sensitivity of anticipatory goal-tracking in the rat to stimulus-food contingency. Contingency was manipulated by varying the probability of food delivery in the absence of a food-tray-light or clicker conditional stimulus (CS), while holding constant the probability of food coincident with the CS. CS control of anticipatory food tray investigation was examined after a period of context extinction in all experiments. Acquisition of stimulus control was undermined by the scheduling of intertrial food deliveries (Experiment 1). The rate of intertrial food deliveries influenced subsequent acquisition of CS control when all intertrial food deliveries were omitted (Experiment 2). When intertrial food deliveries were added to the training regimen subsequent to acquisition of CS control, that control was impaired (Experiments 3 and 4). PMID- 8210454 TI - Radiation therapy for malignant astrocytomas in adults. AB - High grade (or malignant) astrocytomas remain a formidable therapeutic challenge. The main prognostic factors are patient age, patient performance status, tumor grade, the extent of surgical resection and the presence of fits. These factors could help to identify different groups of patients and should be an advantage in deciding on treatment strategies. Modern imaging techniques provide a more precise idea of tumor volume. The study of tumor recurrence shows that they occur in the immediate vicinity of the primary site. Surgery aside, radiotherapy remains the most important treatment modality. Currently, its standards concerning optimal dose and target volume appear to be accepted overall. There is no doubt that a dose-response relation exists; however, doses exceeding 60 Gy increase morbidity. Therefore 60 Gy is the dose most often cited in the literature. Furthermore, as whole brain irradiation does not decrease the risk of recurrence, a focal irradiation including a defined mean volume is generally used today. Radiosensitizers and heavy particles have not fulfilled their initial promise. Brachytherapy remains an interesting alternative for a limited number of patients. Nevertheless, it seems to increase recurrence at a distance from the primary site and to lead to severe focal lesions. Interstitial thermoradiotherapy may minimize local doses and thus help avoid serious local necrosis. Amongst the other therapeutic alternatives, intravenous chemotherapy using nitrosoureas provides a certain but modest benefit. Other administration modalities are currently undergoing evaluation. These include intra-arterial chemotherapy or high dose chemotherapy with auto-bone marrow transplantation. The interest of this latter is concerned mainly with anaplastic astrocytomas. Finally, among the future alternatives, gene therapy appears to hold the most promise. Intensive therapies, combined modality treatments, with the recent help of biological innovations, should be proposed to favorable groups of patients. PMID- 8210455 TI - High-resolution computed tomography of the lungs in irradiated breast cancer patients. AB - Fifty-five breast cancer patients underwent high-resolution computed tomography (HRCT) of the lungs before, 8-12 weeks, 6, 9 and 12 months after adjuvant radiotherapy. During the follow-up time, 17 of them (30%) were found to develop minimal parenchymal alterations in the irradiated lung volume by HRCT evidence. The parenchymal alterations were classified by five scores. Scores 1-4 described chronic radiologic changes, score 5 acute radiologic changes. Three patients presented with acute radiologic changes (alveolar filling) within the first 3 months after radiotherapy. Two did not show any abnormalities at later follow ups. Chronic radiologic fibrosis (15 patients) was not seen before the sixth month post irradiation except in 2 cases. There was no correlation between acute changes and chronic fibrosis. None of these changes were seen at a lung dose of less than 40 Gy. The appearance of interstitial pulmonary lesions secondary to breast irradiation was comparable to that of other interstitial diseases of the lungs. Chest radiographs were normal in all patients. None of the 55 patients presented with clinical symptoms. PMID- 8210456 TI - Preliminary results of a hyperfractionated dose escalation study for locally advanced adenocarcinoma of the prostate. AB - The objective of this study was to build on our experience with 3-D conformal radiotherapy (CRT) by using a hyperfractionated dose escalation scheme to maximize the therapeutic ratio between improved local control and reduced morbidity in patients with locally advanced prostate cancer. Twenty patients with locally advanced (T3, T4) adenocarcinoma of the prostate were treated with a hyperfractionated radiotherapy schedule. All fields were designed with a conformal therapy based beam's eye view, 3-D planning system. The pelvic lymph nodes received 1.8 Gy/day to a total dose of 45 Gy in 5 weeks. Using partial transmission blocks, the prostate and periprostatic tissues received 1.3 Gy twice daily (minimum interval of 6 h) to a total dose of 78 Gy in 6 weeks. The dose was chosen by calculating the biologically effective dose (BED) which would produce the same effect in late reacting tissue but an increase for the tumor as our standard dose of 69 Gy delivered in 1.8-2.0 Gy fractions. The alpha/beta chosen for late damage was 3 Gy and 10 Gy was used for the tumor. All 20 patients completed the planned course of treatment. Although an increase in the tumor BED would be expected to result in increased acute effects, no significant worsening of acute side-effects was observed compared with standard treatment. All patients had only mild (Grade 1) rectal or bladder toxicity during treatment. One patient had an exacerbation of diverticulitis during treatment requiring hospitalization for antibiotics but completed treatment on schedule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210457 TI - Chemoradiation therapy for anal cancer: radiation plus continuous infusion of 5 fluorouracil with or without cisplatin. AB - Chemoradiation therapy for anal cancer was carried out in 58 patients using low dose, continuous infusion of 5-fluorouracil (5-FU) with or without continuous infusion of cisplatin (cDDP) and external beam irradiation (chemoXRT). Thirty nine patients received 5-FU chemoXRT resulting in a local control rate of 50% in those receiving a total dose of < 45 Gy, 73% for those receiving 50-54 Gy, and 83% for those receiving > 60 Gy. The actuarial local control rate at 2 years was 77% after chemoXRT alone; overall local control was 67% at 5 years. In 18 patients receiving 5-FU plus cisplatin with radiation doses of 54-55 Gy, actuarial local control was 85% at 2 years. Fifteen patients failed chemoXRT, 13 of whom had abdominoperineal resection for salvage; the overall local control rate was 93% (54/58). The actuarial survival at 5 years was 81% for the 5-FU chemoXRT group and 94% at 2 years for the 5-FU plus cisplatin chemoXRT group; median follow-up was 54 and 20 months, respectively. Diarrhea and nausea were the most frequent early reactions and were ameliorated by limiting the duration of chemotherapy to 5 days/week and by using XRT techniques to exclude the small bowel from the radiation portal. Serious late radiation complications have not been observed and may be related to XRT fractionation and the use of protracted chemotherapy infusion. The absence of late morbidity coupled with the high local control rate by the use of this chemoXRT program is an area to investigate for improving the therapeutic ratio for the treatment of anal cancers. PMID- 8210458 TI - Radiation-induced damage of the Wistar rat heart: biochemistry and function. AB - A time sequence study was performed on Wistar rats to investigate the early effects of radiation on the mechanical function and energy metabolism of the heart. Two series of rats were exposed to 20 Gy electron irradiation to a field including the heart and approximately a third of the lungs. The hearts were excised at varying time intervals (8-180 days) post irradiation. In one series of hearts the mechanical function was measured using the isolated perfused working rat heart model. At the end of the perfusion the hearts were freeze-clamped for analysis of the high energy phosphate contents (ATP, ADP, AMP and creatine phosphate). In the second series, mitochondria were isolated and the oxidative phosphorylation function measured polarographically (substrate: glutamate). Maximal depression of mechanical function was observed at 60 days post irradiation. Thereafter the work performance of these hearts improved significantly, almost reaching control levels after 180 days. The mitochondrial oxidative phosphorylation function (as measured on the total mitochondrial population) was significantly depressed 30-120 days post irradiation. As in the case of the mechanical changes, the depression was transient and after 180 days post irradiation, values similar to those of controls were obtained. Myocardial high energy phosphates remained unaltered throughout the experiment. PMID- 8210459 TI - The effect of dose fractionation on radiation injury in the rat stomach. AB - Localized 300 kV X-irradiation of the rat stomach with single and fractionated (two and five fractions given daily and in 4 weeks) doses was performed. In the second and third week after irradiation acute radiation gastritis developed which resulted in a dose-dependent drop in body weight. The alpha/beta value for a 10% drop in body weight was calculated to be 9.6 Gy (95% confidence interval 2.1-25.9 Gy). Between 4 and 40 weeks after irradiation subchronic radiation damage was observed which presented itself as atonic dilatation of the stomach. For this effect, the alpha/beta value is 4.8 Gy (graphical estimation) and 5.3 Gy (95% confidence interval 0.4-13.1 Gy; direct Poisson model). In the five-fraction (5F) experiment a significant increase in tolerance amounting to 0.8 Gy/day for the acute effect and 0.4 Gy/day for the subchronic effect was observed when intervals were increased from 1 day to 1 week. In a separate experiment animals were pre irradiated with subtoxic and toxic radiation doses. One hundred days later acute tolerance to a second irradiation was completely restored. However, no recovery of subchronic damage was observed. PMID- 8210460 TI - Spheroid control of malignant glioma cell lines after fractionated irradiation: relation to the surviving fractions at 2 Gy and colony forming efficiencies in a soft agar clonogenic assay. AB - Spheroid control doses (SCD50) were determined for ten human glioma lines after fractionated irradiation under oxic conditions. In addition, SF2 values and colony forming efficiencies (CFE) were measured in a soft agarose clonogenic assay. A significant relationship existed between the SCD50 values and the SF2 CFE data pairs (p = 0.01) but the SCD50 values were higher than expected from the SF2 and CFE values. This comparison shows the influence of environmental factors (different in both model systems) on reproductive tumour cell death after irradiation. PMID- 8210461 TI - Thermosensitization by lowering intracellular pH with 5-(N-ethyl-N-isopropyl) amiloride. AB - It has previously been reported that amiloride, a diuretic drug, sensitizes cells to hyperthermia by inhibiting the Na+/H+ exchange through the plasma membrane and thus decreasing the intracellular pH (pHi), particularly in a low extracellular pH (pHe) environment. In the present study, the efficacy of 5-(N-ethyl-N isopropyl) amiloride (EIPA), an analog of amiloride, to lower the pHi and sensitize tumor cells to hyperthermia was investigated. It was observed that 10 microM EIPA was as effective as 500 microM amiloride to lower the pHi and to increase the thermal sensitivity of SCK tumor cells in vitro. The fact that lowering the pHi and increasing thermal sensitivity of tumor cells by EIPA are more pronounced in acidic medium suggests that the acidic intratumor environment may be exploited to selectively increase the thermal damage in tumors relative to normal tissues by EIPA or its analogs. PMID- 8210462 TI - Case #5. Cinnamon-induced stomatitis. PMID- 8210463 TI - Labor shortage or cheap labor? PMID- 8210464 TI - Preceptorship raises issues of quality assurance, professional liability. PMID- 8210465 TI - Treat all bodily fluids as potentially infectious risk. PMID- 8210466 TI - Building a solid foundation of trust. PMID- 8210467 TI - Papilla reflection procedure allows better access during debridement. PMID- 8210468 TI - Vasoconstrictors. PMID- 8210469 TI - Knowledge or nursing knowledge? PMID- 8210470 TI - Body size values of white and black women. AB - The purpose of this naturalistic study was to compare values held by 36 white and 31 black women related to body size, and to identify factors that influence these values and linkages between body size values and weight management activities. Black women of lower SES were significantly different from black women of higher SES and white women, regardless of SES, in that they were heavier, viewed themselves as heavier, and perceived attractive body size as heavier. Black lower status women had to become a great deal heavier than the other groups before they defined themselves as overweight. We suggest that black lower social status women have a wider range of "normal" and attractive body size and that this wider range is developed from comparisons of other women in their social milieu and influences the initiation of weight loss activities. PMID- 8210471 TI - The confidence of Latina mothers in the care of their low birth weight infants. AB - The growing numbers of Latina mothers with low birth weight (LBW) infants in U.S. hospitals prompted an investigation of maternal confidence and caretaking ability in this group. A sample of 54 Mexican-born, Latina mothers with LBW infants was compared with a group of 25 who had full-term infants. Unexpectedly, there was no significant difference in the perceived maternal confidence of the two groups. Behaviors indicative of sensitivity and competence in caretaking, assessed in mothers with LBW infants, did not correlate with maternal confidence. Factors correlated with maternal confidence and caretaking behavior were the mother's age, education, and parity, as well as the infant's birthweight, weight at discharge, and medical complications. Weight at discharge correlated with caretaking behaviors. The strongest predictor of maternal confidence was parity, followed by infant health (fewer medical complications). These factors together accounted for 25% of the variance in confidence, suggesting that other factors that contribute to maternal confidence of Latina mothers need to be identified. PMID- 8210473 TI - Empirical evidence for the Social Stress Model of Substance Abuse. AB - The Social Stress Model of Substance Abuse builds upon and integrates knowledge from numerous psychosocial theories and models. According to this model, the likelihood of an individual engaging in drug abuse is a function of the stress level and the extent to which it is offset by stress modifiers such as social networks, social competence, and resources. This article synthesizes current empirical evidence for this model. Thirty-five primary research studies are described, with special attention to the four psychosocial constructs inherent in the model: stress, social networks, social competence, and resources. Consistencies and inconsistencies in the findings, a critique of key methodological issues, and suggestions for future research are provided. PMID- 8210472 TI - Factors associated with use of safer sex practices among college freshmen. AB - The purpose of this exploratory study was to examine the relationship of knowledge of AIDS, misconceptions about AIDS, knowledge of safer sex practices, perceived susceptibility, and future time perspective to the practice of safer sex behaviors in 352 single, sexually active, college freshmen. Data were analyzed using stepwise multiple regression analysis and discriminant analysis. There were too few black females for analysis. Future time perspective explained the most variance in safer sex practices for black males. Knowledge of AIDS, perceived susceptibility, misconceptions about AIDS, knowledge of safer sex practices, and future time perspective did not explain a significant amount of variance in use of safer sex practices for either white males or females. However, perceived susceptibility and future time perspective differentiated sexually active from nonsexually active white males and females. PMID- 8210474 TI - Factors influencing home care nursing problems and nursing care. AB - This study was conducted to determine the contributions of sociodemographic factors, medical conditions, and nursing dependency to nursing problems identified and nursing care provided to patients during a home care nursing visit. Patient interviews, direct observation of nursing care, record abstraction, and nurses' reports were used to obtain data from 438 patients receiving nursing visits from a certified home health agency. Nursing dependency was the strongest predictor of the nursing problems of and nursing care provided to home care patients. Measures of nursing dependency should be incorporated in models to determine the extent of nursing problems and nursing care provided in the home and in models of home care nursing reimbursement. PMID- 8210475 TI - Current nursing practice related to sexuality. AB - Nurses' practices related to sexuality were examined using the Survey on Sexuality in Nursing Practice (SSNP). The sample consisted of 155 practicing, registered nurses from a variety of practice settings. Twenty percent of subjects indicated they were never involved in any sexuality-related activities and only about 12% addressed sexuality with a majority of their clients. Although subjects consistently identified sexuality as a necessary part of nursing practice, few addressed sexual concerns with clients. Weighted least squares analysis of 12 variables revealed that only those variables measuring practice setting and area, nurses' knowledge, responsibility, and comfort were useful predictors of nurses' practice related to sexuality. PMID- 8210476 TI - Computer-assisted qualitative research. AB - The use of computer technology has emerged as a significant component in qualitative research methodology. This article differentiates between mechanical and conceptual activities in qualitative analysis and discusses the interplay between them. Advantages of computer technology in the mechanical activities of data management and concerns about the use of computer programs in conceptual/analytic activities are discussed. Guidelines for the judicious application of computers in qualitative research are outlined. PMID- 8210477 TI - Sum-of-products variables: a methodological critique. AB - Sum-of-products variables are integral to testing certain psychological theories (e.g., the theory of reasoned action). A sum-of-products variable is a total score computed by multiplying the scores for corresponding items from two scales and then adding the products. This type of variable is associated with methodological difficulties, however. The purpose of this article is to discuss certain methodological issues associated wtih the use of sum-of-products variables in health-related research. PMID- 8210478 TI - Cardiac ultrasound: state of the art. PMID- 8210479 TI - Magnetic resonance imaging of the heart: state of the art. PMID- 8210480 TI - Diagnostic imaging of the pericardium. PMID- 8210481 TI - Diagnostic imaging of primary cardiomyopathies. PMID- 8210482 TI - Combined diagnostic imaging of acquired valvular disease. PMID- 8210483 TI - Combined diagnostic imaging of congenital heart disease. PMID- 8210484 TI - The role of imaging in heart transplantation. PMID- 8210485 TI - Emergency in cardiovascular diseases. PMID- 8210486 TI - Diagnostic imaging of pulmonary embolism. PMID- 8210487 TI - Chest roentgenology and angiography of the ischemic heart disease. PMID- 8210488 TI - Release of tachykinins and its metabolism in the airway. PMID- 8210489 TI - Preprotachykinin mRNA expression in the synovial tissue of chronic arthritis. PMID- 8210490 TI - Capsaicin pretreatment increases inflammatory response to intratracheal instillation of endotoxin in rats. PMID- 8210491 TI - Characterization of NK-2 binding sites in rabbit lung tissue. PMID- 8210492 TI - Potentiation of sensory tachykininergic and parasympathetic cholinergic transmission by epidermal growth factor. PMID- 8210493 TI - Involvement of tachykinin and CGRP receptors in the cardio-pulmonary effects evoked by capsaicin in the guinea-pig. PMID- 8210494 TI - SR 48968, a neurokinin A (NK2) receptor antagonist. PMID- 8210495 TI - On the presence of NK2 receptor subtypes in peripheral and central tissues. PMID- 8210496 TI - Characterization of the cardiovascular and behavioral effects of centrally administered neuropeptide K in the conscious rat. PMID- 8210497 TI - CP-99,994, a nonpeptide antagonist of the tachykinin NK1 receptor. PMID- 8210498 TI - Increased synthesis of neurokinin B and enkephalin after chronic haloperidol treatment. PMID- 8210499 TI - Signal transduction and ligand-binding domains of the tachykinin receptors. PMID- 8210500 TI - Expression of Krev-1 and c-H-ras proto-oncogenes in the rat spinal cord and the effects of noxious stimulation. PMID- 8210501 TI - Stimulation and propagation of the ascending enteric reflex contraction: role of tachykinins and acetylcholine. PMID- 8210502 TI - Tachykinin receptors in the rat isolated uterus. AB - Tachykinin receptors mediating uterotonic effects were examined in preparations from oestrogen-primed rats. In the absence of peptidase inhibitors [Lys5-MeLeu9 Nle10] NKA (4-10) was 14-fold more potent than neurokinin A (NKA), but the two peptides were equipotent in the presence of phosphoramidon alone and in combination with amastatin. The NK-2 receptor antagonist SR 48968 antagonised responses to the tachykinins. These findings indicate that an NK-2 receptor is present in the oestrogen-primed rat uterus and that endopeptidase 24.11 plays a major role to inactivate NKA in this tissue. PMID- 8210503 TI - Mapping the ligand binding site of the NK-1 receptor. PMID- 8210504 TI - A novel, selective radioligand, [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10), for the tachykinin NK-2 receptor. AB - A new radioligand, [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10), based on the selective agonist [Lys5,MeLeu9,Nle10]-NKA(4-10) has been developed. Binding in rat fundus membranes was displaced by NP gamma > NKA > or = [Lys5,MeLeu9,Nle10] NK(4-10) > neuropeptide K > [Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10) > SP > [Sar9,Met(O2)11]-SP >> senktide, indicating binding to NK-2 receptors. Preliminary studies demonstrated high specific binding in membranes from rat urinary bladder, duodenum and colon. Specific binding in rat brain and lung was negligible, and binding in a range of guinea-pig tissues was no more than 35% specific. These data may indicate species differences in NK-2 receptors. PMID- 8210505 TI - 3.3 kb of 5' flanking DNA from the rat preprotachykinin gene directs high level expression of a reporter gene in microinjected dorsal root ganglion neurons but not in transgenic mice. PMID- 8210506 TI - Four novel tachykinins in frog (Rana catesbeiana) brain and intestine. PMID- 8210507 TI - Arthropod venoms affecting cell signalling system. PMID- 8210508 TI - Characterisation, CNS distribution and function of NK2 receptors studied using potent NK2 receptor antagonists. PMID- 8210509 TI - The renin-angiotensin system in the brain: an update 1993. AB - The renin-angiotensin system is considered to be one of the most important hormonal systems in the regulation of blood pressure and body fluid homeostasis. Ever since this system has been demonstrated to be present also in the brain, vast efforts have been made in investigating its central impact and function. The last few years, and especially the development of non-peptidic angiotensin II receptor subtype specific antagonists and the subsequent pharmacological characterization of these subtypes, brought this field of research a large step forward. This progress also might have opened up new avenues of developing highly specific anti-hypertensive drugs and thereby new ways of treating hypertension. This paper intends to provide a summary of the knowledge about the brain renin angiotensin system accumulated during recent years; an update 1993. PMID- 8210510 TI - Effects of bradykinin on the canine proximal colon. AB - The canine proximal colon set up in Ussing chambers responded to the serosal addition of bradykinin (BK) with changes in short-circuit current (Isc). Two preparations were used to analyze these effects - an innervated mucosal preparation and a 'functionally nerve-free' epithelial preparation. The specific questions that this study sought to answer were (1) is there a significant neural component to the effects noted?, and (2) what is the receptor subtype involved? BK produced dose-dependent increases across both the mucosa and the epithelial preparations. A secondary decrease in Isc was noted in the mucosal but not the epithelial preparation. Tetrodotoxin (TTX) significantly inhibited the magnitude of mucosal responses and delayed their onset as well, indicating the presence of a significant neural component. Addition of the B2 antagonist, D Arg0[Hyp3,Thi5,8, D-Phe7]BK produced a surmountable inhibition of the responses to the agonist. The B1 selective agonist, des-Arg9BK produced increases in Isc across both preparations, though TTX had no significant effects on these responses. Cross-desensitization was seen between BK and des-Arg9 BK. However, since the B1 selective antagonist, des-Arg9[Leu8]BK acted as a partial agonist in our preparation, these effects could not be defined further. Clearly, B2 receptors are involved in mediating canine colonic BK responses, however the role of B1 receptors in this tissue requires further definition. PMID- 8210511 TI - Gonadotropin-releasing hormones, including a novel form, in snook Centropomus undecimalis, in comparison with forms in black sea bass Centropristis striata. AB - The molecular forms of gonadotropin-releasing hormone (GnRH) in brain-pituitary extracts were determined for snook Centropomus undecimalis and black sea bass Centropristis striata. The extracts were analyzed in both isocratic and gradient high performance liquid chromatography (HPLC) programs. Eluted fractions were tested in radioimmunoassays with 4 different antisera made against 3 distinct GnRH peptides. Results show that snook contain 3 forms of GnRH, all of which are present in males and females irrespective of the stage of the reproductive cycle. Larger quantities of these GnRH peptides are present in snook in the nonreproductive phase than in snook in the reproductive phase. One form of snook GnRH is immunologically and chromatographically similar to salmon GnRH, and a second form is similar to chicken GnRH-II. However, the third snook GnRH appears to be distinct from the 7 known forms of the vertebrate hormone. In contrast, sea bass contain only the salmon GnRH-like and chicken GnRH-II-like forms of GnRH and, hence, appear to match the more usual pattern of GnRH peptides in teleosts. We speculate that one of the GnRH genes was duplicated and then altered in a fish ancestral to snook but not sea bass, even though both species of fish are in the recently evolved Perciformes order. PMID- 8210512 TI - Sympathetic nerves, but not the adrenal gland, contribute to elevated plasma levels of met-enkephalin in rats with acute cholestatic hepatitis. AB - Met-enkephalin is known to circulate in human and animal plasma in low levels. However, the source(s) of plasma met-enkephalin have not been completely elucidated. It has been proposed that the adrenal gland, sympathetic nerves, pancreas and the gut might be implicated. Recently, markedly elevated levels of met-enkephalin have been documented in the presence of liver disease. To investigate potential sources of met-enkephalin in liver disease, rats with acute cholestatic hepatitis 24 h after gavage with alpha naphthylisothiocyanate (ANIT) 100 mg/kg were studied. Plasma met-enkephalin levels were determined by radioimmunoassay in plasma samples from normal, adrenalectomized, or chemically sympathectomized animals. In control rats, ANIT treatment resulted in a striking 8.7-fold increase in systemic venous met-enkephalin levels (inferior vena cava) (P < or = 0.0005) and a significant increase in peptidase-derived met-enkephalin levels (determined after trypsin/carboxypeptidase B digestion of plasma samples) (P < or = 0.05). ANIT-treatment also resulted in a 5.6-fold increase in portal vein met-enkephalin levels (P < or = 0.005). Portal vein met-enkephalin levels were only 1.2-fold higher than IVC levels in ANIT-treated rats (P < or = 0.05). Plasma activities of the two main enkephalin degrading enzymes, aminopeptidase and enkephalinase, were similar in control and ANIT-treated rats. Chemical sympathectomy, prior to ANIT treatment, decreased the elevation in inferior vena caval met-enkephalin levels by 35% (P < or = 0.005). Adrenalectomy did not alter ANIT-induced increases in circulating met-enkephalin levels (pNS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210513 TI - Inhibitory effect of neurotensin on proline. AB - The effect of neurotensin (NT) on proline absorption across rat jejunum was investigated using the single-pass perfusion technique. This study showed that intravenous administration of NT produced a dose-dependent inhibition of proline absorption. Thus, NT at a 0.16 pmol/kg/min concentration gave 10% decrease in proline absorption while 0.32 and 1.6 pmol/kg/min concentration gave 31% and 45% decrease, respectively. In the absence of Na, proline absorption decreased to 77% from control values. No change in proline absorption was noticed when NT at a concentration of 0.32 pmol/kg/min was intravenously injected in the absence of sodium from the perfusion solution. Water absorption did not show significant changes (P > 0.05) in presence or absence of NT. Moreover, NT did not produce a significant change (P > 0.2) in intracellular proline accumulation. NT inhibited proline absorption through an indirect mechanism that is Na-dependent and independent of changes in water absorption. PMID- 8210514 TI - Intracisternal neutral endopeptidase-24.11 inhibitors produce inhibition in gastric acid output: independence from opiate, bombesin, or neurotensin-mediated mechanisms. AB - Intracisternal (ic) injection of the neutral endopeptidase-24.11 inhibitor phosphoramidon (1-100 nmol) produced a dose-dependent inhibition of gastric acid secretion in 2-h pylorus-ligated rats. The response resulted from a reduction in acid concentration and volume. Likewise, ic injection of another neutral endopeptidase-24.11 inhibitor Zincov (200 nmol) produced a 63% inhibition in gastric acid output. In contrast, neither intravenous injection of phosphoramidon (100 nmol) nor ic injection of the aminopeptidase inhibitor amastatin (100 nmol) produced any change in gastric acid secretion. The inhibitory effect of ic phosphoramidon (10 nmol) was not reversed by a dose of naloxone sufficient to antagonize the acid inhibitory effects of ic [D-Ala2-D-met5]enkephalinamide (8.5 nmol). Moreover, phosphoramidon-induced inhibition of acid was not reduced by the centrally effective bombesin antagonist N-acetyl-GRP(20-26)-O-CH3 or by reserpine pretreatment at a dose effective to antagonize ic neurotensin-induced inhibition in acid secretion. These results suggest that an endogenous neutral endopeptidase 24.11 sensitive substrate may act in the brain to inhibit gastric acid output by mechanisms independent of CNS opiate, bombesin or neurotensin activity. PMID- 8210515 TI - The rabbit saphenous vein: a tissue preparation specifically enriched in NPY-Y1 receptor subtype. AB - Neuropeptide Y (NPY), a co-transmitter in noradrenergic sympathetic nerves of the cardiovascular system, was tested on isolated segments of rabbit saphenous vein. NPY caused strong, long lasting and concentration dependent contraction resistant to adrenergic blockade. PYY, a NPY related peptide, shared this property. As pressor agents, both peptides were about 100-fold more potent than norepinephrine and at their highest concentrations caused a contraction of a similar magnitude as NE. Gradual shortening of N-terminal end of the NPY molecule caused major loss of potency and reduction of intrinsic activity; which suggests that the entire molecule is required to produce full biological activity in this vascular preparation. Addition of [Leu31,Pro34]pNPY, a NPY analog with specific agonist properties at Y1 receptors, mimicked the effect of NPY whereas NPY (13-36), a selective agonist at Y2 receptors, caused a 2 log unit shift to the right of the concentration response curve. These results suggest that the vasoconstrictor effect of NPY in rabbit saphenous vein results from a direct effect on smooth muscle cells and that the receptors involved are of the Y1 subtype. PMID- 8210516 TI - Peptide histidine methionine and vasoactive intestinal peptide levels in human cerebrospinal fluid: age-related changes and absence of a correlation with serum prolactin. AB - Serum levels of prolactin (PRL), peptide histidine methionine (PHM) and vasoactive intestinal peptide (VIP) were measured in 97 subjects and cerebrospinal fluid (CSF) levels of PHM and VIP were measured in 50 subjects by specific radioimmunoassays to investigate correlations between them. The chromatographic studies revealed that PHM and C-terminal extended form of PHM, peptide histidine valine occurred in human serum and CSF. Significant age-related increases of CSF PHM (P < 0.02) were observed in both males and females, whereas an age-related decrease of serum PRL level was found in females (P < 0.01). In contrast, neither serum VIP, serum PHM nor CSF VIP changed significantly with age. There was a significant positive correlation (P < 0.002) between VIP and PHM in serum, but not in CSF. The close relation between VIP and PHM in serum meets one's expectation because of their derivation from a common precursor. In CSF, these two peptides did not change in parallel with each other. These results may reflect the alteration in metabolism of PHM in CSF. Finally, there was no correlation between serum PRL concentrations and either serum or CSF levels of the peptides, suggesting that neither VIP nor PHM levels in CSF as well as in serum can influence the basal PRL secretion in subjects without endocrine disorders. PMID- 8210517 TI - N-terminal fragments of intestinal cholecystokinin: evidence for release of CCK-8 by cleavage on the carboxyl side of Arg74 of proCCK. AB - From porcine duodenal mucosa we have identified three major procholecystokinin (proCCK) fragments: desoctaCCK-33, desnonaCCK-33 and desnonaCCK-39. (DesoctaCCK 33 means CCK-33 devoid of the 8 C-terminal amino acids, etc.). The fragments were purified by immunoaffinity chromatography and three steps of reverse phase HPLC monitored by a radioimmunoassay specific for the N-terminal part of CCK-33. The structures could be deduced from the proCCK sequence by N-terminal sequence determination and mass spectrometry. Whereas desnona-fragments of CCK have been described before, this is the first finding of a desoctaCCK, and it indicates that CCK-8 is released from the longer forms by endogenous cleavage of the Arg Asp-bond. A carboxypeptidase B-like exopeptidase subsequently must produce the desnona-fragments by removing the arginine residue. PMID- 8210518 TI - Sensory neuropeptide release by bradykinin: mechanisms and pathophysiological implications. AB - Bradykinin (BK) and related kinins excite primary sensory neurons, thus leading to the activation of sensory impulses. More recently, both functional and neurochemical evidence have been accumulated that BK evokes release of neuropeptides, including calcitonin gene-related peptide and the tachykinins substance P and neurokinin A, from peripheral terminals of capsaicin-sensitive primary afferents. The present article will review the mechanisms and the pathophysiological implications of the ability of BK to release sensory neuropeptides at the peripheral level. An account of the clinical studies performed on this subject will be also given. PMID- 8210519 TI - Human chromostatin inhibits endothelin-1-induced contractures in human blood vessels. AB - Isolated endothelium-denuded segments of the human internal thoracic artery (ITA) and saphenous vein (SV) have been used for characterization of vasoinhibitory effects of the chromostatin (hChs) sequence of human chromogranin A (CGA124-143). In SV preincubation with hChs inhibited the response to depolarizing high K+ in Ca(2+)-free medium in a concentration dependent manner (EC50 approximately 2 nM). At 200 nM hChs the tension response to high K+ (80 mM) was inhibited by 44% (n = 8) and the tension response to noradrenaline (2.6 microM) was inhibited by 20% (n = 6), but the tension response to endothelin-1 (65 nM) (ET-1) was not affected. In ITA no effect of hChs was observed on tension response to K+ or ET-1 in Ca(2+) free medium. On the other hand, in Ca(2+)-containing medium the tension evoked by 65 nM ET-1 was no longer sustained in segments preincubated with 200 nM hChs and declined spontaneously to 76 +/- 12% (n = 6) of maximal tension after 6 min. A vascular function for the Chs sequence of the human CGA is thus indicated, inhibiting different components of vasoconstrictor responses in the human SV and ITA segments. PMID- 8210520 TI - Circulatory and metabolic responses in awake dogs to infusion of iso-rANP/(rBNP). AB - We reported that a second rat atrial peptide, iso-atrial natriuretic peptide (iso rANP(1-45)) and a potential putative homologue, iso-rANP(17-45) (identical with rat brain natriuretic peptide except for one amino acid) elicited circulatory and renal responses in anesthetized rats. In the present studies, low-dose intravenous infusions of iso-rANP(1-45) (6.3-25 pmol kg-1 min-1) and iso-rANP(17 45) (12.5-50 pmol kg-1 min-1) into conscious dogs produced subtle circulatory effects compared to control studies. Relative to oxygen consumption, cardiac output was lower and total peripheral resistance higher with both iso-rANP(1-45) and iso-rANP(17-45). Heart rate tended to be slightly lower relative to control studies during peptide infusions, and the highest infusion doses caused a decrease in mean arterial pressure. Plasma protein increased and plasma osmolality decreased with iso-rANP(1-45); infusion of iso-rANP(17-45) caused a decrease in the respiratory exchange ratio. The mechanism of action of iso-rANP may have been direct, via an active receptor. However, we previously reported for these same experiments that infusion of iso-rANP(1-45) and iso-rANP(17-45) increased plasma ANP and decreased plasma renin activity. Thus, circulatory changes during infusion of iso-rANP were consistent with an indirect mechanism related to increased endogenous ANP. PMID- 8210521 TI - Degradation and inactivation of human atrial natriuretic peptide by human pulmonary plasma membranes. AB - Atrial natriuretic peptide (ANP) is extracted from plasma during its passage through the lungs. ANP is metabolized in rat lung membrane preparations by the enzyme neutral endopeptidase-24.11 (EC 3.4.24.11), but the hydrolysis of ANP in human lung has not been characterized. In the present study synthetic human atrial natriuretic peptide 1-28 (alpha-hANP) was separately incubated with human pulmonary plasma membranes from two non-smoking patients, and the major degradation products were separated from alpha-hANP by reverse-phase high pressure liquid chromatography. The degradation products were identified by sequence analysis and by mass-spectrometry, and biological activity was studied in vitro by exposing precontracted rabbit pulmonary arteries to alpha-hANP and the degradation products. The initial cleavage appeared, with membrane preparations from both patients, in the central ring structure between Arg14 and Ile15, followed by a cleavage of the bond Arg3-Arg4 at the N-terminal region of the peptide. The biological activity of this ring-opened product was about 1/500 of the activity of uncleaved alpha-hANP. Cleavage of the Arg3-Arg4 or Arg14-Ile15 bonds could not be inhibited by EDTA, iodoacetamide, benzamidine hydrochloride or pepstatin A. Neither did phosphoramidon (1 microM) or thiorphan (1 microM) inhibit the hydrolysis, indicating the presence in human lung of an ANP-degrading enzyme different from endopeptidase-24.11. PMID- 8210522 TI - The neurogenic origin of hypertension in SHR may be mediated by angiotensin II through a receptor different from AT1 and AT2. AB - In spontaneously hypertensive rats (SHR) 15-18 weeks old, the intracerebroventricular (icv) administration of peptide angiotensin II (Ang) antagonists results in a short (30-60 min) decrease (15-25 mmHg) of blood pressure (BP). Both EXP-3174, a known metabolite of Losartan and AT1 selective, and PD-123177, a receptor AT2 specific compound, do not affect SHR BP following icv administration. The receptor AT1 selective non-peptide Ang antagonists, Losartan and L-158809, induce long-lived (days) significant BP reductions (< or = 40 mmHg) in SHR, but only 18 h after icv injection. The slow development of BP reduction and its persistence might be due to the formation of an active metabolite, different from EXP-3174, a Losartan metabolite. In older SHR (25-28 weeks), the hypotensive effect of Losartan and L-158809 is not significant. These results suggest that in the CNS of the young SHR, an active Renin-Ang-System is implicated in the establishment of the hypertensive state, and that the receptor for this function is different from AT1 and AT2, since it has a selectivity profile different from AT1 and AT2 receptor types. PMID- 8210523 TI - Bayliss and Starling 13th Annual Meeting. London, 13-14 September 1993. Abstracts. PMID- 8210524 TI - [Prolegomena to non-ionizing radiation energy. Biological effects and radiation protection]. PMID- 8210525 TI - [Computerized tomography in the evaluation of anatomic variations of the ostiomeatal complex]. AB - This work was aimed at showing the main anatomical variations in the ostiomeatal complex which are usually depicted by CT. A hundred and thirty CT exams including 59 normal cases (45.4%) and 71 cases of chronic sinus disease (54.6%) were reviewed. The following anatomical variations were considered: concha bullosa, middle turbinate, septum, uncinate process and bulla changes, Haller cells and agger nasi cells. Anatomical variations were demonstrated in 69 patients--31 normal subjects and 38 patients with chronic sinusitis. The incidence of every anatomical variation was investigated and the results were compared with literature data. Excluding agger nasi cells, which were seen in nearly all patients, the most common variations were concha bullosa and septal spur and deviations, while the least common variations were those in the middle turbinate and uncinate process. PMID- 8210526 TI - [Fibrous dysplasia of the skull. Radiologic diagnosis]. AB - The authors examined 11 patients with fibrous dysplasia of the skull pointing out its radiologic features and preferential sites. Conventional radiology, CT and MR imaging were used. As for conventional radiology, tangential scans which of great value to depict the most typical morphologic patterns. Lesions of the skull base were most frequent in the sphenoid (7 of 11 cases), where 5 of 7 exhibited a sclerotic pattern. Bone changes in the skull vault were: mixed (3 cases), pagetoid (2 cases), "ground glass" (1 case) and lytic (1 case): none of these cases was of the sclerotic type. A typical feature of vault lesions was the widening of diploic space associated with expansion of the outer bone and integrity of the inner bone. Radiologic findings, often associated with suggestive clinical manifestations, always allowed a diagnostic hypothesis; histopathologic confirmation was needed only in a few cases (4 of 11 patients). PMID- 8210527 TI - [Diagnostic imaging of Tietze's syndrome. Comparison of computerized tomography and ultrasonography]. AB - Tietze's syndrome is an uncommon disease characterized by the absence of any systemic symptom; imaging techniques play a major role in the diagnosis of this condition. A control group including 10 normal subjects and 4 patients with clinical evidence of Tietze's syndrome were submitted to US; 3/4 patients underwent CT too. In the lesion site, US demonstrated thickened cartilage and inhomogeneously increased echogenicity in 4 patients, blurred outline in 3 patients and a hypoechoic halo in 1 patient. CT showed thickened cartilage and blurred outline in 3 patients and hypodense cartilage in 1 patient. Both methods were very useful to diagnose the disease in all cases. The authors conclude that US plays a major role in the diagnosis of Tietze's syndrome thanks to its harmlessness, repeatability and cost-effectiveness. PMID- 8210528 TI - [Lung interstitial disease in systemic sclerosis: semiologic characteristics with high-resolution computerized tomography and comparison with other methods]. AB - In 28 patients with systemic sclerosis interstitial lung involvement was investigated with high-resolution Computed Tomography (HRCT) in comparison with other diagnostic methods (respiratory function tests, lung scintigraphy and conventional radiography of the chest). The most frequent CT signs were: interlobular septal thickening, intralobular interstitial thickening, and ground glass density. Their distribution was generally basal and posterior and high correlation was observed between the extent of lung disease and the cutaneous pattern of scleroderma. Pathological findings were present in 93% of cases: HRCT can must be considered more effective than the other methods in the evaluation of systemic sclerosis and should therefore be a fundamental diagnostic tool in the study and follow-up of interstitial diseases in the patients with systemic sclerosis. PMID- 8210529 TI - [Diagnosis with high resolution computerized tomography of early asbestos-induced diseases]. AB - This study was aimed at investigating the possibility of detecting lung and pleural asbestos-related lesions by means of conventional chest films and high resolution Computed Tomography (HRCT) in a study population of asymptomatic workers of a shipyard factory in northwestern Tuscany, Italy. Thus, a blind study was carried out by two radiologists who reviewed 144 conventional chest films previously considered as negative by outside readers. Thirty-eight of 144 workers were selected, whose conventional films had been confirmed as negative, together with 34 more subjects with suspected pleural plaques or mild parenchymal involvement (ILO profusion score: 0/1). These 72 subjects were submitted to HRCT: 19 of them were negative, while in 33 cases pleural plaques were found; 7 workers exhibited parenchymal involvement alone, while in 13 both pleural and parenchymal alterations were found. HRCT findings were correlated with the duration of amosite exposure and the latency time since first exposure. Relative to conventional radiographs, the threshold of exposure and latency times allowing asbestos-related diseases to be demonstrated was markedly lower. Our study suggests that pleural and/or lung involvement in asbestos-exposed workers can be shown by HRCT before the onset of clinical symptoms or the appearance of pleural/parenchymal involvement on chest films. Moreover, the HRCT-detectable lung and/or parenchymal involvement appeared to be related to exposure and latency times, as in most of clinically-apparent asbestos-related lung diseases. PMID- 8210530 TI - [Systematic evaluation of the pulmonary circulation with computerized tomography: normal and post-embolic pathologic features]. AB - Pulmonary circulation was evaluated in normal subjects and in post-embolic patients. Eight normal subjects, 3 patients with acute pulmonary embolism and 8 patients with chronic thromboembolic pulmonary hypertension underwent CT of the chest. High-resolution CT and angio-CT were performed to study pulmonary parenchyma and pulmonary arteries, respectively. CT showed thrombi in the main or interlobar pulmonary arteries in all 3 cases of acute pulmonary embolism and in 4 of 8 patients affected with chronic thromboembolic pulmonary hypertension. The diameters of the main pulmonary and right interlobar arteries correlated with systolic pulmonary artery pressure (p < 0.001), as measured by right heart catheterization. In the patients affected with chronic thromboembolic pulmonary hypertension, the ratio of the calibers of the segmental arteries to the corresponding bronchi was markedly higher, which was observed also in the patients with acute pulmonary embolism. The bronchial arteries were dilated in 4 of 8 cases of chronic thromboembolic pulmonary hypertension. Lung density was significantly high in the perihilar compartment in the patients with acute thromboembolic hypertension, but not in normal controls and in the cases of acute pulmonary embolism. In conclusion, CT can help to diagnose pathological pulmonary circulation. Particularly, the ratio of the diameters of the segmental arteries to the corresponding bronchi can be useful to evaluate blood circulation. PMID- 8210531 TI - [CT-guided thoracic biopsy. Personal experience with DBNH Haaga 20 G needles]. AB - CT-guided fine-needle biopsy of the chest is nowadays a conventional diagnostic procedure, which can be furtherly improved so as to increase its diagnostic sensitivity and to reduce complications. We studied a series of possible improvements over a 2-year period (1990-1992). In our radiology department 164 CT guided biopsies were performed in 130 men and 34 women. DBNH Haaga 20-G (15 cm) needles (Cook, Denmark) were used. This kind of needle is a coaxial cutting-edge needle used for simultaneous cytological and histological sampling. Exams were performed with a Philip Tomoscanner CX-S (scanning time: 2.8 seconds). Of 164 tissue samples, 153 (93.4%) were adequate for histological diagnosis. As for suspected neoplastic disease, our results demonstrated 108 true positives, 27 true negatives, 18 false negatives and no false positive. Sensitivity, specificity and diagnostic accuracy were 85.7%, 100% and 88.2%, respectively. In 24 cases there were minor complications--i.e., 5 cases of parenchymal hemorrhage and 19 cases of minor pneumothorax. In one case only there was major pneumothorax which required surgical drainage. On the basis of our experience, we suggest the use of such coaxial catheters as the DBNH Haaga type for the collection of both histological and cytological material because this needle reduces the need for repeated invasive and potentially dangerous maneuvers. PMID- 8210532 TI - [Quality assurance of mammography in the province of Trent]. AB - In 1991, a second program for quality control in mammography was carried out in the Physics Department of the Trento Hospital. All the six mammographic centers around Trento entered the study and 9 mammographic units were thus considered. Two main types of measurements were obtained: a) determination of the physical variables affecting radiologic system optimization; b) evaluation of image quality and average breast dose, according to DQM program criteria. The film variables, mean gradients and base plus fog level, the half-value layer (HVL) and the entrance exposure free in air were scored as acceptable in all cases. The average breast dose was calculated on the basis of literature data, given the entrance exposure free in air, the HVL and the focus-skin distance values. All the mammographic units but one were scored as "D" (acceptable) on the average breast dose curve, which is defined by the national average value obtained during phase II of the DQM program. This Quality Control program allowed all mammographic units to be optimized and also emphasized the need for periodical quality controls. PMID- 8210533 TI - [Role of magnetic resonance in the follow-up of surgically treated aortic dissection]. AB - Twenty-one patients were examined with MRI 0.5 to 200 months after surgical aortic dissection. The series included 15 type-I dissections, 1 type-II dissection and 5 complicated type-III dissections. MR images demonstrated the persistence of the intimal flap with patency of both the true and the false lumen in 17 cases, the complete obliteration of the false lumen in 1 case and the partial thrombosis of the false lumen in 3 cases. Coronary artery ostial reimplantation was depicted in all the patients who underwent this kind of surgery; in 1 case, a small hematoma was present at the site of reimplantation. In 3 patients, an organized hematoma was seen between the prosthetic graft and the native aortic wall; in 1 case the aortic lumen was markedly reduced, while in the extant 2 cases, signal intensity features were suggestive of subacute hematoma due to prosthetic graft degeneration. Seven patients underwent two MR exams: the first one immediately after surgery (in most cases) and the second one at 3-11 months. Aortic diameter progressively increased in 4 patients, 3 of them with Marfan syndrome. In conclusion, MRI proved an accurate technique to assess aortic size beyond the prosthetic graft and to demonstrate the residual dissecting process and the postoperative problems in the prosthetic conduit. PMID- 8210534 TI - [Carotid bifurcation: angiography with magnetic resonance versus carotid angiography]. AB - The reliability of Magnetic Resonance Angiography (MRA) was investigated in the study of stenosis and obstruction of carotid bifurcation; digital carotidography was the gold standard. Twenty-five consecutive patients with clinical suspicion of cerebrovascular insufficiency entered the study. MRA was performed with a 1.5 T superconductive magnet (Magnetom Siemens) and a linear head coil. The TOF 3D (FA 20 degrees, TR 30 ms, TE 7 ms) technique was applied. Images were acquired on the sagittal plane and rotated in postprocessing according to MIP on the z axis from 60 to 120 degrees (step 5). MRA exhibit 80.5% sensitivity, 96% specificity, 89.4% accuracy, 94.7% positive predictive value and 86.3% negative predictive value. When calculating the interrupted flow relative to hemodynamically significant stenoses (range 31%-occlusions), MRA sensitivity was 80.5%, specificity 100%, negative predictive value 86.3%, positive predictive value 94.7% and overall diagnostic accuracy 91.2%. MRA is to be considered a diagnostically reliable procedure in the study of carotid bifurcation and its diagnostic accuracy may even be increased in the future by the possible assessment of over- and underestimated cases. PMID- 8210535 TI - [Arterial anatomy of the celiac trunk and the superior mesenteric artery with computerized tomography]. AB - A hundred patients with different conditions underwent CT and the results were retrospectively reviewed to evaluate the visibility of the celiac trunk, of its branches and of the superior mesenteric artery. Thirty-six patients underwent angiography too, which allowed the anatomical variants suspected on CT to be demonstrated, according to Kuhns' criteria. The other 64 patients were consecutively selected and only aneurysmal changes were not included. All examinations were performed using a General Electric 9800 Advantage scanner, with 2 second scanning time and 10 mm-thick contiguous scans. In 20 patients 5 mm contiguous scans were performed. All examinations followed i.v. injections of contrast agents which were given with an automatic injector. The cases with suspected anatomical variants on CT but with no angiographic confirmation were not considered. A hundred CT exams were retrospectively reviewed: the celiac trunk and the common hepatic artery were demonstrated in all of them. Visibility of the other branches was 40% for the hepatic artery, 53% for the right branch of the hepatic artery and 39% for its left branch, 70% for the gastroduodenal artery, 82% for the left gastric artery, 97% for the splenic artery and 100% for the superior mesenteric artery. As for the 36 patients who underwent both CT and angiography, right hepatic artery from the superior mesenteric artery was seen in 19% of cases with both modalities; common hepatic artery arising from the superior mesenteric artery was detected in 2% of cases. In both instances, these anatomical variants appeared as a vessel running posterior to the portal vein. The careful investigation of axial CT scans showed the level of origin of the artery from the superior mesenteric artery. These results are in agreement with the angiographic data reported in the literature. Our study demonstrated that the celiac trunk and its variants are always depicted by the new CT scanner. The knowledge of these variants may be useful in the patients to submit to liver surgery. The celiac trunk and its variants are demonstrated with conventional 10 mm slices. The use of 5 mm slices improves the visibility of thin anatomical branches but is not essential to recognize the major vessels and anatomical variants. PMID- 8210536 TI - [Comparison of ultrasonography, computerized tomography, and magnetic resonance in the study of parotid masses]. AB - One hundred and seven patients were examined to compare advantages and pitfalls of the imaging methods currently used to stage parotid masses. Thirty patients underwent US and CT, 44 were investigated with US and MRI and 33 with US, CT and MRI. The accuracy of the three techniques was analyzed in detecting and assessing the intra-/extraglandular location of the parotid lesions and their benign/malignant nature. The intraglandular lesion spread to superficial/deep lobes was also investigated, together with its relationship to the surrounding structures. The findings were correlated with the cytohistological data from US guided biopsy or from surgical resection. US was less accurate than CT and MRI, the latter being not statistically superior to the former. Because of the low incidence of pitfalls, US with fine-needle aspiration cytology should be the technique of choice; CT and MRI must be used for lesions > 3 cm or for masses in the deep gland lobes. In conclusion, CT accurately assesses parotid lesions but MRI demonstrates the relationship to adjacent structures better. PMID- 8210537 TI - [Echo-color Doppler in the study of hypothyroidism in the adult]. AB - Color-Doppler US was performed on 20 patients with sub-clinic hypothyroidism which had been confirmed by laboratory tests. In all cases, color-Doppler US showed increased parenchymal flow, whose semiology was similar to the one known as "thyroid inferno" and currently associated, in the literature, with diffuse hyperfunction conditions. Quantitative measurements yielded no further element for differential diagnosis, while showing high flow speeds which were similar to those in hyperfunction. On the basis of consequent physiopathologic considerations, hypervascularization, as observed in hypothyroidism, is likely to be referred to the hypertrophic action of TSH, which was reported as high in all patients. In conclusion, the color-Doppler "thyroid inferno" pattern, which has been to date considered as specific of thyroid hyperfunction, has lost part of its diagnostic specificity, and further investigation--e.g. hormonal titers, scintigraphy--is needed for an unquestionable diagnosis to be made. PMID- 8210538 TI - [Gadolinium-DTPA dimeglumine administered orally for the study of the abdomen with magnetic resonance. Clinical evaluation and tolerance]. AB - The tolerance to and the clinical value of a new positive oral contrast agent, Gd DTPA-Dimeglumine, were evaluated. Ten healthy volunteers and 30 patients with abdominal and pelvic tumors were studied. Fourteen patients underwent MR scans only after cm administration, while 16 patients were examined both before and after. All images were obtained by means of a 1.5-T MR unit using SE and GE pulse sequences on the axial and coronal planes. Before the examination, a 1-mmol Gd DTPA-Dimeglumine solution with mannitol and sodium citrate diluted in 1L of water was administered to all patients in 100-150-ml fractions. The product was well tolerated and its taste was good; adverse reactions were uncommon and mild. The solution was stable during gastrointestinal tract transit. Bowel signal was hyperintense on both GE and SE pulse sequences, which clearly demonstrated the bowel lumen distinguishing it from the surrounding fatty tissue and depicting even the smallest vascular structures. Moreover, from a clinical point of view, the hepatic, pancreatic and colic borders were better demonstrated in both normal and pathologic conditions. PMID- 8210539 TI - [Metallic stents in benign biliary stenosis. A four-year follow-up]. AB - From October 1988 to September 1989, 29 self-expanding biliary metallic stents were positioned in 18 patients with recurrent benign biliary strictures, who were no longer candidates to surgical repair and did not respond to percutaneous balloon dilatation. "Z" stent were used in 17 patients and a Wallstent in one case. At four years' follow-up (range: 39-50, average: 46 months), 10 patients remain asymptomatic, without signs of bile stasis (55.5%), five patients had recurrence of symptoms and were subsequently retreated (27.7%) and three patients died from severe underlying diseases, two of them with stent obstruction, one without signs of bile stasis. Recurrences were caused by stent obstruction in three cases. At four years' follow-up the overall patency rate is 68.7%. According to the type of stricture treated, patency is 100% in the group of patients with single CBD stenosis and in the patients with single anastomotic strictures, whereas in all patients with multiple or complicated strictures the stents completely occluded within 4-22 months. PMID- 8210540 TI - [Transluminal therapy of stenosing lesions of the supra-aortic vessels. Personal experience]. AB - Percutaneous transluminal angioplasty (PTA) is commonly used to treat peripheral vascular diseases, but its use has recently spread to the treatment of stenotic lesions involving the supra-aortic vessels. The authors report their initial experience in 10 patients with left subclavian artery stenoses--8 of them treated with PTA and 2 with PTA and vascular stenting--and two more patients with fibromuscular stenosis of the internal carotid artery (ICA), which was treated by means of PTA. In the authors' opinion, PTA can be considered the procedure of choice to treat the stenotic lesions of the supra-aortic vessels. Intravascular stents can be extremely useful to prevent post-PTA restenosis, but further experience and probably further technological refinements are needed. To conclude, PTA of ICA is an effective method in selected cases--e.g., in the patients with symptomatic hemodynamic lesions and low risk of embolism, in the patients with difficult surgical access or in the event of high anesthesiological and/or surgical morbidity. PMID- 8210541 TI - [Percutaneous stenting in the treatment of iliac steno+-obstructive lesions]. AB - The authors report their experience with Palmaz stents in the percutaneous treatment of steno-obstructive iliac artery lesions. A hundred and thirty-six patients suffering from claudicatio, pain at rest or distal lesions underwent 156 percutaneous stenting maneuvers. The indications to stenting were: acute obstruction or severe dissection after angioplasty (19 cases), residual stenosis > 30% (80 cases), large ulceration (7 cases), restenosis after previous percutaneous treatment (10 cases) and finally chronic obstruction (40 cases). In 154 cases the maneuver was successful, in 2 the stent was mispositioned because of technical problems and another stent had to be inserted. In 146 cases stenting was performed after transluminal angioplasty, while 10 chronic obstructions underwent stenting with no previous angioplasty to limit distal embolization. In all cases stenting improved the angiographic pattern more than angioplasty alone. Prophylactic drugs after stenting included only anti-aggregating substances. Marked clinical improvement was observed after stenting, and almost all patients gained at least one clinical stage. During stenting, 15 complications occurred (9.6%)--i.e, 2 external iliac artery dissections, 4 mild inguinal hematomas, 1 pseudoaneurysm, 1 segmental obstruction of the superficial femoral artery and 7 distal embolisms during recanalization of chronic occlusions. The complications were caused by the procedure, and especially by the large caliber of the introducer sheat; no complication was related to the stent itself. None of these complications needed major surgery. Over 3-34 months' follow-up (mean: 9 months), 1 obstruction and 2 restenoses occurred in 134 vessels; these lesions were treated successfully with thrombolysis and/or transluminal angioplasty (primary patency: 97.8%, secondary patency: 100%). In the authors' experience, percutaneous stenting represents a simple and fast procedure with very good technical and clinical results which can increase the capabilities of percutaneous revascularization procedures. PMID- 8210542 TI - [The role of cellular kinetics as a predictive index of response to radiotherapy: state of the art and future perspectives]. PMID- 8210543 TI - [Effects of immunomodulation on antineoplastic radiotherapy. A controlled clinical study]. AB - It is well known that thymic hormones can counteract immunodepression due to radiation therapy, preventing and reducing the severity and the number of myelotoxic and hematologic reactions. We tried to confirm these findings in a controlled multicenter clinical study involving 1,060 patients undergoing radiation therapy (580 treated with thymopentin 50 mg s.c. every other day, after irradiation and for at least 6 cycles of 4 weeks each, and 480 control patients). Highly statistically significant results (to the ANOVA test) were obtained in the protection against radiation-induced leukopenia in the treated group; furthermore, the treated patients had a marked reduction (p = 0.003 chi 2 test) in the early delayed reactions to irradiation, namely in the upper aero-digestive tract. In general, we observed a better, but not statistically significant recovery of the blood parameters, lymphocyte subsets and skin tests in the treated group versus the control group. Both of the treated groups showed the same trend for Karnofsky performance status and body weight. The local and general protection provided by thymopentin against the reactions to irradiation could be advantageously used for the administration of higher doses of radiation therapy. PMID- 8210544 TI - [The irradiated volume in stage III non-small-cell carcinoma of the lung. Comparison of outdated and new techniques]. AB - March 1988 through April 1992, three hundred and ninety-six patients affected with bronchogenic carcinoma were treated at the Department of Radiation Oncology of the S. Anna Hospital, Como, Italy. A hundred and ten patients presenting stage III non-small-cell lung carcinoma were evaluable. All evaluable patients underwent radiation therapy alone, with either palliative or curative purposes. Two main periods can be distinguished: in period A, before June 30th, 1990, treatment planning included conventional techniques, with no simulators; the patients were treated with opposing anteroposterior fields only. In period B, after July 1st, 1990, either the simulator alone was used or a simulator, a CT unit and a treatment planning computer system were combined; anteroposterior opposing fields or multiportal technique were used. Median overall survival was 10 months. Independent of treatment goals, the irradiated volume was markedly different in the patients treated in period A than in those treated in period B. A marked and statistically significant increase in survival was observed in group B. Survival also increased in patients treated with doses > 40 Gy, but only if treatment planning had used adequate technology and accuracy. To conclude, better survival can be achieved only by improving treatment accuracy and quality. PMID- 8210545 TI - [Congenital sternal malformations]. PMID- 8210546 TI - [Radiologic criteria of aggressiveness and considerations regarding a case of peripheral chondrosarcoma]. PMID- 8210547 TI - Asphyxiating thoracic dystrophy without respiratory disease. PMID- 8210548 TI - [Pneumomediastinum related to cocaine use. Description of a case]. PMID- 8210550 TI - [Foci of lobular carcinoma in situ within breast fibroadenoma studied with ultrasonography. A case report]. PMID- 8210549 TI - [Primary seminoma of the mediastinum. Description of a case and review of the literature]. PMID- 8210551 TI - [Unusual cause of obstruction of the Stensen's duct. A case report]. PMID- 8210552 TI - [Incidental finding of unusual duodeno-rectal fistula in a patient with Crohn disease]. PMID- 8210553 TI - [Pelvic pheochromocytoma extending to the spine. A pediatric case]. PMID- 8210554 TI - [Perirenal spontaneous extravasation of contrast media during urographic examination. Description of a case and review of the literature]. PMID- 8210555 TI - [Post-traumatic chyluria. Presentation of a clinico-radiologic case]. PMID- 8210556 TI - [Diagnosis with combined imaging in a case of von Hippel-Lindau disease]. PMID- 8210557 TI - Atrial natriuretic peptides in the treatment of acute renal failure. PMID- 8210558 TI - Interstitial leucocyte infiltration in primary glomerulonephritis: extent and composition analysis. AB - In the interstitial cell infiltrates associated with primary glomerulonephritis, approximately the same cellular composition has been found, T cells being predominant, monocytes fewer, and B cells least. Cell composition did not seem to be related to the cell density; the lowest percentages of monocytes have been observed with either very high (FSGS) or very low (MGN) cell densities; and the highest percentages of T cells, with either the highest (FSGS) or the lowest (MGN) cell densities. On the other hand, some relationship seemed to exist with the cell distribution in the interstitium. The cell composition was nearly the same in diffuse and disseminated patterns, but was markedly different in nodular (focal) cell infiltrates; T cells were always in first place, but B cells instead of monocytes were in second place. Furthermore, IL2-receptor-presenting cells have been more often observed in nodular (focal) than in both diffuse and disseminated patterns, and more markedly in nonjuxtaglomerular than in juxtaglomerular noduli (foci). In conclusion, cell composition of interstitial infiltrates seems to reflect a cell-mediated immune reaction, leading to all interstitial cell infiltrates associated with primary glomerulonephritis. It is conceivable that the nodular (focal) pattern of distribution might correspond to a discrete mechanism and have a different meaning. PMID- 8210559 TI - Rat renal functions during the first days post-bile duct ligation. AB - Renal functions during the early stage of hepatic damage before ascites formation were studied in adult female rats. Tubular and hemodynamic parameters were analyzed for 12 days after common bile duct ligation. The fractional excretion of water, sodium, and potassium increased from control values at every day studied. Glomerular filtration rate and renal plasma flow were found to be diminished on the fourth day. Renal plasma flow remained decreased while glomerular filtration rate was recovered on the sixth day after common bile duct ligation. Filtration fraction in both experimental groups (4 and 6 days) was higher than in control animals. These observations suggested a preferential efferent arteriole vasoconstriction that could be responsible for a blood flow redistribution to the medulla. This fact might cause the sodium diuresis with diminished urine-to plasma osmolalities ratio. The onset of cortical vasoconstriction was confirmed by dopamine infusion to bile duct-ligated rats 4 days postsurgery. Hemodynamic and tubular parameters recovered to control values during dopamine administration. All the data point out diuresis and natriuresis as the earliest renal abnormalities in bile duct-ligated rats. This phenomenon could be associated not only to the cortical vasoconstriction proposed but also to another systemic modification associated to liver damage. PMID- 8210560 TI - Characterization of gentamicin-induced dysfunctions in vitro: the use of optimized primary cultures of rabbit proximal tubule cells. AB - Compared to prior studies which frequently pinpoint the impairment of one parameter or function, this paper reports for the first time an extensive characterization of the toxic effects of gentamicin in a single model of primary cultured rabbit proximal tubule cells developed without insulin and glucose. Biochemical, functional and morphological approaches were used. Cellular response pattern was examined after a 72-h exposure during either the exponential growth phase or the stationary confluency phase of the culture to 0.2, 1, and 2.5 mM gentamicin. The biochemical study after gentamicin exposure showed increased activities for N-acetyl-beta-D-glucosaminidase and alkaline phosphatase, decreased activities for sphingomyelinase, cathepsin B, Na+/K(+)-ATPase, lactate dehydrogenase and NADPH cytochrome C reductase. Functional evaluation revealed decreased protein synthesis and alpha-methylglucose transport after gentamicin exposure. Morphometric study made it possible to show that the density of lysosomes, the cell fractional volume of the lysosomal compartment, and the mean size of the lysosomal profiles are increased in the cells. Intracellular accumulation of gentamicin in proximal tubular cells was dose dependent and reached high levels in cultured cells. In conclusion, this model compared to others in the literature allowed us to demonstrate in vitro a close response pattern to the in vivo situation after gentamicin exposure. PMID- 8210561 TI - Methylprednisolone and cyclophosphamide pulse therapy in crescentic glomerulonephritis: safety and effectiveness. AB - In a previous study, we found that aggressive immunosuppressive therapy with continuous high-dose oral steroid and cyclophosphamide combined with plasma exchanges for extracapillary crescentic glomerulonephritis gave controversial results since, although disease activity was controlled, iatrogenic complications had led to death in some aged patients. We then modified our therapeutic regimen, and we analyze here the evolution of 30 consecutive patients who were admitted for biopsy-proven crescentic glomerulonephritis between 1989 and 1991. The mean plasma creatinine level at admission was 393 +/- 59 mumol/L (range 70 to 1100), and 15 patients had crescent formation in more than 50% of glomeruli on initial renal biopsy. Ten patients did not receive any immunosuppressive treatment since they either had a normal renal function or they had terminal renal failure and no severe extrarenal manifestation. The 20 other patients received initial steroid pulses 500 mg x3 (n = 17), low oral steroid treatment (n = 20), cyclophosphamide pulses (n = 13), or oral cyclophosphamide (n = 3). In 4 cases plasma exchanges were also used. As a whole, 10 patients (33%) were discharged with a normal renal function, and 18 patients (60%) had chronic renal failure, 7 of them requiring dialysis or transplantation; only 2 patients died of pulmonary hemorrhage. No severe iatrogenic complication was observed. These results indicate that reduction in oral steroid dosage, cyclophosphamide pulse therapy rather than continuous oral treatment, and plasma exchanges do not induce overimmunosuppression and iatrogenic complication. It can be safe, well tolerated, and as effective as a more intensive immunosuppressive regimen for the treatment of crescentic extracapillary glomerulonephritis. PMID- 8210562 TI - Laminin, fibronectin, and Goodpasture antigen detection in patients with Alport's syndrome. AB - Indirect immunofluorescence study with laminin and fibronectin monoclonal antibodies on paraffin sections, as well as with serum from a patient with Goodpasture's syndrome with high titer of autoantibodies that recognize the antigenic determinants in human glomerular and tubular basement membrane, was performed on 14 patients with Alport's syndrome and 5 specimens of normal renal tissue obtained from donors in cases of renal transplantation (control group). We found no binding of Goodpasture antigen to glomerular and distal tubular basement membranes in renal biopsy tissue from all 14 patients with Alport's syndrome. In contrast, there was bright linear fluorescence of Goodpasture antigen on glomerular and tubular basement membranes of normal renal material. There was no difference in laminin and fibronectin binding in patients with Alport's syndrome and controls. In all the cases binding was strongly positive. These results suggest an abnormality or absence of immunoreactive autoantigen in the glomerular and distal tubular basement membrane in patients with Alport's syndrome. Therefore, Goodpasture antigen detection could be an important diagnostic method in early stages of Alport's syndrome when characteristic morphological changes are not yet developed. PMID- 8210563 TI - Isradipine decreases exercise-induced albuminuria in patients with essential hypertension. AB - The aim of our study was to investigate the effects of exercise on albuminuria and blood pressure in patients with essential hypertension, and the short-term effect of the calcium channel blocker isradipine on exercise-induced albuminuria (UAE) and blood pressure in the same patients. Ten patients (7 males, 3 females) with essential hypertension were admitted to the study. The mean age was 54 +/- 2.7 years and the mean body mass index was 27 +/- 1 kg/m2. Patients performed two physical exercise tests on a cycloergometer. Workload was increased by 30 watts every 2 min until 90% of the theoretical maximal heart rate was achieved. This workload was maintained for 5 min. Samples for albuminuria assay were collected at the end of exercise and 1 h after exercise. The first physical exercise test was performed after 15 days of placebo washout; the second exercise was performed after 10 days of therapy with isradipine 5 mg once daily p.o. After 10 days of therapy with isradipine, UAE immediately after (31 +/- 8.3 micrograms/min) and 1 h after exercise (31.5 +/- 7.3 micrograms/min) were significantly (p < 0.05) lower as compared to the values found after placebo (37.1 +/- 9.3 micrograms/min; 43.5 +/- 9.9 micrograms/min). Our data show that short-term administration of the calcium channel blocker isradipine is able to cause a concomitant significant decrease in exercise-induced pressor and albuminuric response in patients with essential hypertension. The finding that short-term calcium channel blockade can reduce exercise-induced albuminuria in essential hypertensive patients suggests that progression of nephropathy in this early phase could be slowed by isradipine in these patients. PMID- 8210564 TI - Cerebral function analyzing monitor and visual evoked potentials as a noninvasive method of detecting cerebral dysfunction in patients with acute hepatic and renal failure treated with intermittent machine hemofiltration. AB - We monitored the effect of 7 intermittent machine hemofiltration treatments in 4 patients with fulminant hepatic failure who had progressed to grade IV coma and developed acute oliguric renal failure. Prior to treatment the processed EEG showed excess slow wave activity, and the latency of the later visual evoked potentials (N2 and P2) was delayed. Following treatment there was a further increase in both EEG slow wave activity and latency of the N1, N2, and P2 potentials. Intracranial pressure increased from a median of 8 mm Hg (2-12, range) to 14 (8-28) following treatment, p < 0.05. There was a correlation between intracranial pressure and all of the later visual evoked potentials, for N3 r = 0.71, for P1 r = 0.39, and P2 r = 0.74, all p < 0.05. Although there appeared to be a good correlation between intracranial pressure and the noninvasive electrophysiological recordings, there were major changes in intracranial pressure, cerebral perfusion pressure, and cerebrospinal fluid pH during the first hour of treatment, during which time there were no discernable changes in EEG or evoked potentials. In this study, non-invasive neurophysiological methods were not found to be reliable as invasive methods in assessing acute, minute-by-minute changes in cerebral metabolism but these methods may have a role in the longer term in assessing patient prognosis. PMID- 8210565 TI - Impaired antioxidant defense mechanisms in two children with hemolytic-uremic syndrome. AB - In the present study we have assayed antioxidant enzymatic activities of SOD, CAT, GSH-Px, GSH-Red, and G6PD in erythrocytes from two children with hemolytic uremic syndrome (HUS) during the acute phase of the disease and after their recovery; in addition, we have tested the percentage of hemolysis after 24-h incubation in PBS containing glucose (1 g/1000 mL) or in the presence of their own plasma. Endogenous plasmatic MDA levels were also evaluated as lipid peroxidation marker. A significant decrease in SOD activity was found in erythrocytes from HUS patients, and the addition of their own plasma further decreased SOD activity. Elevated percentage of hemolysis was found in HUS patients when RBCs were incubated in their own plasma; this last effect was less evident in PBS + glucose. PMID- 8210566 TI - Suppressive effect of sera from patients undergoing chronic hemodialysis on neutrophil chemiluminescence response. AB - To determine the mechanism of easy infectability of uremic patients, we studied the effect of sera from uremic patients who were undergoing chronic hemodialysis on the chemiluminescence (CL) response of polymorphonuclear leukocytes (PMN). The luminol-dependent CL response was examined following stimulation with phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (FMLP). The patient's sera suppressed the CL response following stimulation by PMA, but not by FMLP. These findings suggest that sera from uremic patients undergoing hemodialysis contain a suppressive substance that suppresses the activation of PMNs by PMA. PMID- 8210567 TI - Diagnosis and treatment of carpal tunnel syndrome. AB - Secondary amyloidosis is a complication typical for patients on long-term hemodialysis. The first clinical signs are usually shoulder joint pain and carpal tunnel syndrome (CTS). We have questioned 74 patients who were on regular hemodialysis (HD) treatment and divided them into 3 groups according to the length of HD. Group 1--on HD for 1-4 years: There were 35 patients in this group, 15 of them (i.e., 43%) had shoulder joint pain and/or CTS. None of these patients had symptoms that would require surgical treatment. Group II--on HD for 5-9 years: There were 22 patients in this group, 15 of them (i.e., 68%) had shoulder joint pain and/or CTS. Three patients from this group had severe night pain and were therefore indicated for surgical treatment for CTS, each of them on 1 hand only. In 2 cases amyloid was present in the histological examination. Group III- on HD for over 10 years: There were 17 patients in this group, 13 of them (i.e., 76%) had shoulder joint pain and/or CTS. Five patients from this group were operated on both hands for severe night pain due to carpal tunnel syndrome. Only 1 patient had positive amyloid on both hands in the histological examination. All the 8 patients (i.e., 13 hands) were examined by EMG before the operation, showing reduction of motor conduction on n. medianus by 30.7 +/- 15.1%. After the operation the EMG control was done in 4 patients (7 hands), showing no improvement in 2 cases and in 5 cases the conduction on the n. medianus was found to be in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210568 TI - Local dissolution of uric acid calculi using THAM-E. PMID- 8210569 TI - The influence of mode of dialysis pretransplantation on long-term renal allograft outcome. AB - To determine the influence of the need and the mode of dialysis prior to transplantation on long-term renal allograft survival and subsequent renal function, all 662 consecutive cyclosporine-treated renal transplants (484 cadaver and 178 living-related donors), performed between 1983 and 1989 were retrospectively analyzed. Recipients were divided into 3 groups as follows: group I and II recipients underwent hemodialysis and peritoneal dialysis, respectively, prior to transplantation; group III patients were transplanted without dialysis. All groups were similar with respect to demographic and immunologic characteristics, apart from a higher proportion of diabetic and White patients in both cadaver and living-related group III recipients and a fewer number of blood transfusions among living-related group III recipients. A trend toward a decreased incidence of dialysis dependence in the early posttransplant period was noted among cadaver donor recipients in group III (20%) when compared to group I and II patients (36% and 26%, respectively). The incidence of rejection episodes was similar in all groups. No difference in 1- and 5-year patient survival was noted among all recipient groups. Actual 1-year graft survivals in groups I, II, and III were similar (73%, 72%, and 74%, respectively, for cadaver donor; and 86%, 89%, and 91%, respectively for living-related donor recipients). Likewise, actuarial 5-year graft survivals were not significantly different (53%, 51%, and 67%, respectively, for cadaver donor; and 75%, 69%, and 82%, for living-related donor recipients). Renal function, as assessed by serum creatinine concentration, was similar and stable in all recipient groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210570 TI - Spontaneous blastogenesis profiles and IL-2 receptor expression on kidney allograft. AB - To examine immune activation rate of interstitial and glomeruli infiltrating MNC in different conditions of human renal allograft function deterioration, 33 renal transplant biopsies were performed 1-30 months after transplantations. Forty-one patients observed were on immunosuppressives: Pr, Aza, CsA following renal transplantation from a living-related donor parent. The patients were divided according to their histologic diagnosis into the following groups: 1, 15 pts in acute rejection attack (AR); 2, 10 pts with cyclosporine nephrotoxicity (CsN); 3, 10 pts with chronic vascular rejecting kidney (ChR). A conventional histologic investigation and immunohistochemical analyses of CD3 and CD25 molecules were performed in groups 1-3. Spontaneous blastogenesis (SB) of peripheral lymphocytes was simultaneously determined and compared with the controls (C)-30 healthy people, and with patients with stable renal allograft function (S)-8 pts. The highest IL-2R expression on diffuse or focal dense MNC infiltrates in interstitium was observed during AR, without IL-2R+ MNC in glomeruli. Low to moderate focal interstitial infiltrates in damaged areas of renal parenchyma due to CsN, were IL-2R negative. In ChR, moderate IL-2R expression was observed on interstitial spare mild or focal dense MNC infiltrates with IL-2R expression present on glomeruli infiltrating MNC. Significant increases of SB values were recorded during the first week after transplantation and AR in comparison to C. The highest SB values were in ChR group. Values of SB in CsN and S were on the C and before transplantation levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210571 TI - Hemolytic-uremic syndrome during recombinant alpha-interferon treatment for hairy cell leukemia. AB - We report a case of hemolytic uremic syndrome in a patient suffering from hairy cell leukemia during recombinant alpha-interferon treatment. We believe that this is the first report of the occurrence of this peculiar kind of acute renal failure following alpha-interferon therapy. This association may suggest possible speculations regarding side effects of interferon treatment and pathogenesis of hemolytic uremic syndrome. PMID- 8210572 TI - Corticotropin-dependent Cushing's syndrome in a patient with chronic renal failure--a rare association. AB - Corticotropin-dependent Cushing's syndrome was detected in a 32-year-old male suffering from membranous nephropathy and chronic renal failure. Cortisol dynamics revealed high basal cortisol, loss of circadian rhythm, and nonsuppressibility with low-dose dexamethasone. However, the latter was suppressible with high-dose dexamethasone. Treatment with ketoconazole led to a remarkable response both clinically and biochemically. The occurrence of Cushing's syndrome in a patient with chronic renal failure is extremely rare and poses significant diagnostic and therapeutic problems. PMID- 8210573 TI - Heredity, genes and osteoarthritis. AB - Human osteoarthritis (OA) is a heterogeneous and multifactorial disease with multiple pathogenetic mechanisms implicated in its development and progression. Despite its complex clinical expression, it appears that some forms of OA have a heritable component. This article briefly updates the reader on recent research that addresses the subject of heredity as one of significance in the etiology of OA. PMID- 8210574 TI - Cytokines and inflammation in cartilage degradation. AB - Since the discovery of humoral factors such as cytokines, which could modulate connective tissue metabolism, questions have arisen concerning their involvement in the pathophysiology of osteoarthritis. At least three cytokines, interleukin (IL-1), tumor necrosis factor, and interleukin-6, were identified in articular tissue and suggested to play a role during inflammation. Osteoarthritic chondrocytes have a higher sensitivity to stimulation by IL-1 with respect to metalloprotease production than normal chondrocytes that seem to be related to an increase in the level of IL-1 receptors. Natural antagonists capable of directly counteracting cytokine action on joint cells have been identified; however, their role in osteoarthritis remains to be determined, particularly in the context of their use for therapeutic intervention. PMID- 8210575 TI - The role of growth factors in cartilage metabolism. AB - The formation of articular cartilage defects in osteoarthritis arise due to an imbalance between biosynthetic and catabolic processes affecting the extracellular matrix. The compensatory synthesis of extracellular matrix proteins required to re-established normal cartilage homeostasis may be compromised by the failure of affected chondrocytes to respond to growth-stimulating peptides. Growth factors and cytokines may act synergistically to attenuate or boost chondrocyte responses. An understanding of how chondrocytes in osteoarthritic joints respond to growth factors could aid in the development of a rationale for designing new therapies to control the progression of osteoarthritic pathology. PMID- 8210577 TI - The course of osteoarthritis and factors that affect it. AB - The natural history of knee, hip, and hand osteoarthritis (OA) is variable. Pathologic changes of OA generally remain stable or worsen, although some patients with hip osteoarthritis may actually sustain reconstitution of joint space. Even with stable pathology, patients often experience symptomatic improvement. Risk factors for OA progression include elderly age, coexistent crystal disease, concurrent OA in multiple joints (generalized disease), neuropathy, and, for knees, obesity. PMID- 8210576 TI - Neurogenic factors in the etiopathogenesis of osteoarthritis. AB - In this article we have tried to unify several different lines of evidence bearing on how neuromuscular mechanisms might contribute to the etiopathogenesis of OA. Several key points bear emphasis. (1) The neuromuscular system is both the greatest threat that the joint faces and the principal means by which joints are protected, because this system exercises the definitive influence on the spectrum of forces to which the joint is exposed. If muscle contraction is not properly coordinated, the joint will exceed its normal extreme of excursion and the loading of its cartilage will be excessive. This trauma will be manifest pathologically as OA. It follows that if the neuromuscular system cannot control the mechanical environment of the joint, the articular and periarticular tissues will break down even in the face of treatment with "chondroprotective" drugs. (2) Speculation about the role of sensation in joint protection is pointless unless sensory ablation influences the development of OA. (3) Only a small minority of patients with severe peripheral sensory neuropathy develop a Charcot joint, and a clear correlation between the development of a Charcot joint and the severity of the sensory neuropathy or the activity level of the patient has yet to be established. Until proved otherwise, it should not be assumed that ipsilateral sensation plays a role in protecting the stable joint from breakdown. (4) There have been surprisingly few animal experiments in which the effect of sensory nerve ablation on synovial joints has been examined. Although the results of the early studies are not entirely consistent, they suggest that extensive deafferentation of a limb does not necessarily lead to joint pathology in the absence of exogenous trauma or infection. Such studies should be repeated under carefully controlled conditions. (5) Recent work in dogs suggests that ipsilateral sensation is not important in protecting the stable joint from OA but is necessary to protect the unstable joint from rapid deterioration. Moreover, there is evidence that sensation is temporarily important in protecting the unstable joint but that the CNS eventually acquires the ability to protect the unstable joint even in the absence of ipsilateral sensory input. PMID- 8210578 TI - Exercise: a cause of osteoarthritis? AB - A common question posed to rheumatologists by both patients and physicians is 'What is the role of exercise in arthritis?' Practitioners and patients want to know if regular exercise is a risk factor for the later development of osteoarthritis. This article briefly reviews the epidemiology of osteoarthritis and exercise and risk factors associated with the development of osteoarthritis in athletes. It also reviews how musculoskeletal tissues respond to loading in normal and injured states. Finally, the topic of exercise for arthritic patients is reviewed, and recommendations are given. PMID- 8210579 TI - Body fluid markers of cartilage changes in osteoarthritis. AB - Various markers of the metabolism of articular cartilage have been identified in synovial fluid, blood, and urine of patients with osteoarthritis (OA). The joint fluid level of a cartilage-derived molecule, or its fragment, can be used as a marker of the synthesis or catabolism of that molecule in the articular surfaces within that joint. In blood and urine, on the other hand, the level of a marker is useful in assessing systemic changes affecting the metabolism of a molecule in all the cartilages in the body. Quantification of specific markers in body fluids already has proved useful in identifying increased catabolic as well as anabolic activities in articular cartilage during preradiologic as well as later stages of OA. The markers also can be sued for monitoring the effect of drugs on cartilage matrix molecules and in differentiating among different subtypes of osteoarthritis. Markers should prove most useful in prospective studies aimed at identifying early changes in cartilage metabolism in humans at high risk for developing OA. PMID- 8210580 TI - Radiologic assessment of osteoarthritis. New techniques. AB - Of the newer imaging techniques, magnetic resonance imaging holds promise for earlier detection of features of osteoarthritis (OA). Computed tomography, bone scanning, and ultrasound play very limited roles in evaluation of OA. This article illustrates the uses of magnetic resonance imaging in the detection of OA. PMID- 8210581 TI - The role of arthroscopy in the differential diagnosis of osteoarthritis of the knee. AB - The arthroscope, currently used in OA mostly as a tool to deliver surgical therapy, can play an important diagnostic role in patients with knee pain for whom OA is part of the differential diagnosis. Concepts that may seem foreign to clinicians who take care of patients with knee OA (that is, of arthroscopy as a purely diagnostic tool and of knee OA as a clinical situation for which a differential diagnosis might be rendered) are supported by an appreciation for the heterogeneity of conditions of which OA is a part as well as an awareness of the pathoanatomic complexity of symptomatic knee OA as revealed by recent MRI and arthroscopy studies. Inspection of the perplexing OA knee with one of the newly available needle arthroscopes in an ambulatory office setting may be preferable to referral for conventional operating room--based arthroscopy, as this new technique adequately delineates intra-articular anatomical abnormalities (for which surgical therapy is not always indicated) and provides saline lavage to the joint (considered by many as a major factor in the improvement of symptoms reported by many patients with knee OA after arthroscopy). At present arthroscopy can serve to aid differential diagnostic efforts in five clinical situations involving knee OA: painful swollen knee with normal radiographs and noninflammatory fluid, clinical and radiographic OA with pain out of proportion to radiographic findings and refractory to conventional medical therapy, chronic stable (radiographic) OA with profound worsening of symptoms, OA with predominate "mechanical" symptoms, and OA with unexpected synovial fluid characteristics. Future use of needle arthroscopy in knee OA could serve to define the intraarticular correlates of pain in OA, to identify specific subgroups of knee OA upon which prospective randomized testing of arthroscopic surgical interventions could be conducted, and to quantitatively assess the effects of new treatment modalities on articular cartilage and other intraarticular structures. PMID- 8210582 TI - Should osteoarthritis be treated with nonsteroidal anti-inflammatory drugs? AB - Numerous studies have demonstrated the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) and their superiority to placebo as symptomatic treatment for osteoarthritis (OA). Unquestionably, use of NSAIDs has reduced joint pain and improved mobility for millions of patients with OA. This article explores the uncertainty that exists regarding the use of NSAIDs in the treatment of OA. PMID- 8210583 TI - Cartilage repair and conservation in osteoarthritis. A brief review of some experimental approaches to chondroprotection. AB - Osteoarthritis is the most prevalent rheumatic disease. Inasmuch as osteoarthritis is predominantly idiopathic, current treatment is aimed not at a cure but palliative management. Research, however, has made considerable forward strides with respect to feasibility of new methods for diagnostic markers of early disease and disease progression, as well as methods to conserve articular damage. This article briefly describes the authors' experience with the use of one type of surgical repair and five different medicinal agents for cartilage conservation. PMID- 8210584 TI - Role of abrasion arthroplasty and debridement in the management of osteoarthritis of the knee. AB - The role of arthroscopic debridement for the treatment of degenerative arthritis of the knee is controversial. Success rates are dependent on multiple factors including the age of the patient, degree of arthritis, activity level, and length of follow-up. This article elaborates on and defines the indications and results of arthroscopic treatment of osteoarthritis of the knee and the role of abrasion arthroplasty. PMID- 8210585 TI - Pathophysiology and treatment of intervertebral disk disease. AB - Back pain is like quality--you know it when you see it--but it is hard to precisely identify and quantify all the factors that are responsible for it. Quality of care in back pain compounds this dilemma. Because we cannot often precisely identify specific causes of back pain (we are usually overwhelmed by an excess of putative factors) and we cannot often assess therapeutic results with precision (double-blind randomized studies of multivaried pathologic and psychologic factors and multiple coexistent therapies and compliance variables), assessment of treatment modes is extremely difficult. Nonetheless, we ultimately must treat the patient. Nihilism is unrealistic. The art and science of medicine must be integrated. Pseudoscience based on high-tech dazzle must be viewed with appropriate skepticism. Treatments must enlist patients' understanding of their options with carefully directed self-care and home therapies augmented when needed by proven safe treatments as well as reasonable, inexpensive, safe remedies still lacking proof of efficacy to help comfort and support the patient during the healing process. Surgical interventions, with a few exceptions, are a last resort and should be employed judiciously and skillfully by experienced surgeons. The surgeon also must be both knowledgeable and experienced in the conservative treatment of low back pain to know when conservative treatment has truly failed. Failure to profit from an investment in a poorly managed business does not mean that the business per se has no value but rather that the business can only prosper with committed qualified management. No less can be asked of conservative rehabilitative therapies before they have been judged a bankrupt failure. Conservative treatment of low back pain is not complicated, but it does require knowledge, skill, and persistence and the ability to recognize when its failure is the result of a lack of response to optimal therapy and when further therapy is procrastination, redundant, and wasteful of time, suffering, and resources. PMID- 8210586 TI - MR imaging of bone marrow edema pattern: transient osteoporosis, transient bone marrow edema syndrome, or osteonecrosis. AB - The bone marrow edema (BME) pattern of signal intensity changes on magnetic resonance (MR) images (decreased on T1-weighted and increased on T2-weighted) is a nonspecific finding encountered with several entities, including transient osteoporosis of the hip, transient BME syndrome, osteonecrosis, trauma, infection, and infiltrative neoplasm. Transient osteoporosis, an unusual but distinct syndrome characterized by self-limited pain and radiographically evident osteopenia, can be distinguished from other causes of the BME pattern, particularly osteonecrosis, on the basis of clinical findings and the development of radiographically evident focal osteopenia within 8 weeks after the onset of pain. This is an important distinction, since all patients with transient osteoporosis recover completely, without intervention. The term transient BME syndrome can be used to describe any patient in whom a reversible BME pattern is seen on MR images. Although the transient BME syndrome is also self-limited and quite likely related to transient osteoporosis, the authors believe that to avoid confusion, this nonspecific term should be reserved only for patients who do not develop radiographically evident osteopenia. PMID- 8210587 TI - Manifestations of gastrointestinal disease on chest radiographs. AB - Diseases of the gastrointestinal tract may result in radiographic changes in the thorax. An abnormal chest radiographic finding is often the initial clue to the diagnosis of gastrointestinal disease. This article presents the commonly recognized and some unusual thoracic manifestations of significant primary esophageal diseases including achalasia, diverticula, carcinoma, duplication cysts, varices, esophageal perforation, and postoperative changes. Intraabdominal gastrointestinal processes such as pancreatitis or pseudocysts, gastric and colonic abnormalities, pneumoperitoneum, liver abnormalities, intraabdominal abscesses, and diaphragmatic hernias, which are frequently associated with intrathoracic abnormalities, are also reviewed. Awareness of changes on the chest radiograph produced by gastrointestinal disease allows prompt diagnosis and facilitates the appropriate confirmatory diagnostic study, such as esophagography or computed tomography. PMID- 8210588 TI - CT of the mesocolon. Part 1. Anatomic considerations. AB - To define the anatomy of the mesocolic attachment of the colon as seen on computed tomographic (CT) scans, the authors reviewed CT scans of patients with diseases of the colon and the pancreas and found that disease processes in these areas usually spread along the mesocolon. The plane of the mesocolon can be distinguished from the mesentery of the small bowel by identifying the vessels in the mesocolon that serve as its landmarks. These vessels include the ileocolic vessels and right colic vessels for the ascending mesocolon, the middle colic vessels for the transverse mesocolon, and the inferior mesenteric vein for the sigmoid and descending mesocolon. These vessels can be seen routinely on CT scans of the abdomen and pelvis, and knowledge of the anatomy of the mesocolon can help the radiologist understand and identify the pathways for spread of diseases of the colon and pancreas. Recognition of the anatomy of the mesocolon is also helpful in the identification of the pattern of recurrent disease after treatment. PMID- 8210590 TI - Gastrointestinal tract duplications: clinical, pathologic, etiologic, and radiologic considerations. AB - Gastrointestinal tract duplications are uncommon congenital abnormalities. By definition, they are located in or adjacent to the wall of part of the gastrointestinal tract, have smooth muscle in their walls, and are lined by alimentary tract mucosa. The lining mucosa is not necessarily that of the adjacent segment of the gastrointestinal tract. The only clinically important ectopic tissues are gastric mucosa and pancreatic tissue. Although ectopic gastric mucosa is found in duplications at all levels of the gastrointestinal tract, it is most prevalent (43%) in esophageal duplications. Peptic ulcer within this ectopic tissue can account for unusual, often misleading symptoms. Ectopic pancreatic tissue is most common (37%) in gastric duplications and is associated with pancreatitis and elevated amylase levels. Detection of associated vertebral anomalies is a helpful clue in the radiographic diagnosis of duplications. Barium studies usually reveal an intraluminal, intramural, or extrinsic mass, and ultrasonography (US) demonstrates its cystic nature. When US findings are inconclusive, computed tomography can be used to show the true nature, location, and extent of the lesion, as well as associated vertebral anomalies and possible other duplications. Technetium-99m pertechnetate scintigraphy provides definitive evidence of a duplication when it contains ectopic gastric mucosa and is particularly useful for suspected esophageal, duodenal, and small bowel lesions. PMID- 8210589 TI - Fluorodeoxyglucose PET of abdominal and pelvic neoplasms: potential role in oncologic imaging. AB - Fluorine-18-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) was used to image 38 patients with known or suspected malignant processes involving the abdomen or pelvis (including primary [n = 2] and secondary [n = 19] liver tumors, recurrent colon carcinoma [n = 1], lymphoma [n = 15], and cavernous hemangioma [n = 1]). PET results were compared with those from concurrent computed tomographic (CT) studies. Conspicuity of metastatic liver lesions on PET images often exceeded that of lesions on CT scans. Two well-differentiated primary liver tumors failed to show increased FDG uptake. Thirteen of the 15 patients with lymphoma had active disease, as determined with CT or clinical findings; 12 of 13 had increased FDG uptake on PET images. The false-negative result occurred in a patient with a low-grade lymphoma. The recurrent colorectal lesion was well demonstrated by PET, but further study is needed to determine whether it can be used to distinguish recurrent disease from radiation-induced changes. PET may be useful in determining the response to oncologic therapy, but PET does not reliably allow exclusion of low-grade lymphoma or well differentiated hepatic lesions. Clinical correlation is always required in evaluating the significance of PET findings, as inflammatory conditions can also result in increased FDG uptake. PMID- 8210591 TI - Imaging in pediatric liver transplantation. AB - Liver transplantation is an accepted and successful mode of treatment for pediatric end-stage liver disease. On the basis of a review of 229 liver transplantations in 185 children, the authors describe the imaging findings of the preoperative evaluation, the uncomplicated transplantation, various postoperative complications, and the suggested percutaneous treatment of some of these complications. The most frequent indications for liver transplantation encountered in this review were biliary atresia (52%), acute fulminant hepatic failure (11%), alpha 1-antitrypsin deficiency (9%), cryptogenic cirrhosis (6%), and chronic active hepatitis (4%). (The remaining 18% were various rare indications, representing < 4% each.) Routine Doppler ultrasound is the modality of choice for the screening of postoperative complications, supplemented with computed tomography, hepatobiliary scintigraphy, and cholangiography or angiography as needed. Familiarity with the normal graft appearance, as influenced by various surgical and technical factors, and knowledge of the underlying condition of the patient and the clinical course of postoperative complications are crucial for a correct interpretation of the findings from imaging studies. PMID- 8210592 TI - Clinical medicine is alive and well. PMID- 8210593 TI - Abdominal complications in pediatric bone marrow transplant recipients. AB - Abdominal problems and catastrophes often complicate the clinical course after bone marrow transplantation (BMT) in children. These complications can be grouped into categories of infection, chemotherapy and radiation toxicity, graft-versus host disease (GVHD), recurrent or de novo malignancy, and miscellaneous complications and can involve the hepatobiliary system, pancreas, spleen, gastrointestinal tract, and urinary tract. Infection is common after BMT: the causative organism depends on the changing immunologic state of the recipient and even on environmental factors such as recent construction, humidity, and antibiotic use. Chemotherapy and radiation therapy can cause hepatic veno occlusive disease, pancreatitis, nephritis, and hemorrhagic cystitis. GVHD is a process in which donor lymphoid cells produce damage to recipient target organs, especially skin, liver, and intestinal mucosa. Recurrent or de novo disease or malignancies, particularly B-cell lymphomas, may develop in chronically immunocompromised children. Other problems include stone disease, splenic and renal infarction, and complications of hyperalimentation therapy. Abdominal imaging, including plain radiography, contrast material-enhanced studies of the bowel, real-time and duplex sonography, and computed tomography, is essential in diagnosing these problems and evaluating response to therapy. PMID- 8210594 TI - High performance computing and communications. PMID- 8210596 TI - General case of the day. Angiosarcomatous pulmonary metastases. PMID- 8210595 TI - Cerebellopontine angle masses: radiologic-pathologic correlation. AB - The cerebellopontine angle cistern is a cerebrospinal fluid-filled space bound by the pons, cerebellum, and petrous temporal bone. Masses in this region are readily identified on cross-sectional images. Differential diagnosis of masses in this region can be simplified by using an algorithmic approach that combines morphologic and enhancement characteristics with established demographic data. Schwannomas are enhancing, round masses, most commonly arising from the vestibular nerve near the porus acusticus and associated with enlargement of the internal auditory canal. Meningiomas are enhancing, oval or hemispheric lesions with a broad attachment to the tentorium or petrous dura mater. Congenital epidermoid inclusion cysts are nonenhancing masses that have undulating margins, molding their shape to conform to the adjacent structures. Aneurysms without significant internal thrombus have prominent flow voids on magnetic resonance images. PMID- 8210597 TI - Pediatric case of the day. Aneurysm of the ductus arteriosus and vascular dysplasia. PMID- 8210598 TI - US case of the day. Polysplenia syndrome. PMID- 8210599 TI - Multiple-element transducers. AB - Multiple-element transducers, commonly called arrays, contain groups of transducer elements. The complete name of an array, such as the linear sequenced array, describes both how the array is constructed (linear) and how it is operated (sequenced); however, the names most often used are incomplete descriptions, such as the commonly used linear array. The arrays are arranged as a straight or a curved line of rectangular elements (linear or convex array) or concentric rings (annular array). Except for the annular array, which focuses the beam two-dimensionally but cannot steer it, the arrays electronically scan the ultrasound beam without mechanical movement. The image formats produced are a rectangle, parallelogram, and sector. To improve image quality, arrays can electronically focus the transmitted beam at a desired depth or at multiple depths to, in effect, achieve a long focal region. Focusing of received echoes is also accomplished electronically. Dynamic aperture and apodization also improve image quality with arrays. PMID- 8210600 TI - Endovaginal sonography of the nongravid uterus. AB - Endovaginal sonography allows excellent visualization of the endometrium, including the cyclic changes seen in premenopausal women and the normal postmenopausal endometrium. The spectrum of abnormalities affecting the endometrium and myometrium, including foreign bodies, infection, fluid collections, hyperplasia, and neoplasia, is also best assessed with endovaginal sonography. It has also become the imaging modality of choice for examining women with postmenopausal bleeding. In these patients, analysis of the sonographic appearance of the endometrium, combined with duplex and color Doppler evaluation of the endometrial vasculature, may allow differentiation of benign from malignant processes. PMID- 8210601 TI - Outcomes research: challenge for the 1990s. PMID- 8210602 TI - Duplex and color Doppler sonography of hemodialysis arteriovenous fistulas and grafts. AB - Surgically constructed Brescia-Cimino arteriovenous fistulas and synthetic loop grafts are common means of vascular access for hemodialysis. Although angiography has been the traditional method of imaging these vascular systems, duplex and color Doppler sonography offer a noninvasive method of evaluating dysfunctional hemodialysis access. In normally functioning fistulas, waveforms of flow in the supply arteries and throughout the graft are monophasic, with peak systolic velocities of 100-400 cm/sec and end-diastolic velocities of 60-200 cm/sec. The draining veins have arterial pulsations with peak velocities of 30-100 cm/sec. Arterial and venous stenoses, graft thrombosis (occlusive and nonocclusive), infection, aneurysm and pseudoaneurysm formation, and arterial steal are relatively common abnormalities that can threaten or destroy graft function and can be diagnosed sonographically. Although abnormal hemodynamics in access fistulas are usually detected during hemodialysis, sonographic evaluation at the time of initial dysfunction may reveal an underlying correctable abnormality, and specific therapy may be instituted before the condition progresses. In addition, use of sonography may obviate an invasive angiographic examination if no significant hemodynamic problem is present. PMID- 8210603 TI - Evaluating facilitated communications of people with developmental disabilities. AB - A quasi-experimental message-passing procedure was used to assess the validity of the facilitated communication (FC) by people with autism and mental retardation or with mental retardation. The 23 participants were classified as having intellectual skills within the range of severe to profound mental retardation. Message-passing consisted of showing and verbally labeling a picture of a familiar object with the facilitator absent, and subsequent facilitation to generate a label or description of the object. Three-trial blocks were conducted with each participant on two different days. Blocks were conducted in the participants' normal FC setting, with their facilitators of choice, and no special apparatus was used. No participant was able to accurately label or describe the object shown to them with facilitation. Possible reasons for findings set forth by proponents of FC and findings from the emerging quantitative literature on FC are considered. PMID- 8210605 TI - Community integration of young adults with mental retardation: a multivariate analysis of adjustment. AB - The purpose of the present study was to determine whether differences in community adjustment existed for three groups of young adults with mental retardation using data organized on the basis of four empirically validated factors identified in prior research. A descriptive discriminant function analysis was used as a follow-up to a statistically significant multivariate analysis of variance F-ratio. Results obtained from the discriminant analysis indicated that five variables (number of limiting factors, earned income, number of support services, living arrangement, number of daytime activities) contributed substantively to separation of the three group centroids. PMID- 8210604 TI - The relationship between functional assessment and treatment selection for aggressive behaviors. AB - Functional assessment seeks to elucidate the variables controlling a maladaptive behavior. Based on such an assessment, effective treatments can be designed that focus on replacing that maladaptive behavior with a functionally equivalent adaptive prosocial behavior. This technique has been promoted as an effective means of improving treatments by increasing the focus on skill development and reducing the use of aversive and restrictive procedures. The literature for the behavioral treatment of aggression for persons with mental retardation or developmental delays was examined from 1979 through 1990. During that period the use of functional assessment and skill training increased; however, the increased use of functional assessment did not result in the reduced use of intrusive procedures. Potential reasons for these results are discussed, and a call for an increased emphasis on functional assessment methodology is made. PMID- 8210606 TI - Growth hormone response after administration of L-dopa, clonidine, and growth hormone releasing hormone in children with Down syndrome. AB - We studied the response of growth hormone secretion after the administration of L dopa, clonidine, and growth hormone releasing hormone in eight growth-retarded children with Down syndrome aged 1 to 6.5 years. After L-dopa administration, five children had low growth hormone secretion (M = 3.7 ng/ml, SD = 2.12 at 30 min) and three children had elevated growth hormone levels (> 30 ng/ml). After clonidine administration, six children had relatively low growth hormone levels (M = 3.15 ng/ml, SD = 2.53 at 60 min) and two children had high levels (38.3 ng/ml and 16.8 ng/ml, respectively). There was a better response after growth hormone releasing hormone administration; only one child had a growth hormone level of < 10 ng/ml. Most of the children had a modified response of growth hormone secretion subsequent to the various stimulation tests. All children, however, were able to secrete some growth hormone (> or = 10 ng/ml) at least during one of the stimulation tests. In comparison with peak growth hormone levels reported in normal children, our cohort had significantly lower growth hormone levels only after clonidine administration. It is postulated that children with Down syndrome have both anatomical and biochemical hypothalamic derangements that may result in decreased growth hormone secretion and reduced linear growth. In addition, other mechanisms that may be in part responsible for the observed growth retardation are discussed. PMID- 8210607 TI - Assessment of depression in mentally retarded adults: reliability and validity of the Children's Depression Inventory (CDI). AB - The applicability of the Children's Depression Inventory (CDI) in the informant rating version to mentally retarded adults (> 19 years of age) of all degrees of severity is researched here for the first time. The sample (N = 798) consisted of residents in community-based group homes (56.9%) and residents of a variety of institutions (43.1%). On average, 23 of the 24 CDI items were to be assessed. Internal consistency, interrater reliability, and the item-total score correlations were adequate. The three factors derived from factor analysis were open to clear interpretation. The CDI score proved to be independent of age, sex, and degree of mental retardation. Persons with behavior problems, psychotropic drug treatment, non-Down syndrome status, as well as the residents of a psychiatric clinic, all returned a higher CDI score. Among those having a CDI score > or = 17 (n = 54), there were 57% with DSM-III-R depressive disorders. These results suggest that the CDI in an informant-rating version is suitable as a diagnostic and screening instrument for mentally retarded adults. PMID- 8210608 TI - Grief in adults with mental retardation: preliminary findings. AB - Structured direct interviews of 43 adults with mental retardation were conducted to evaluate how they express grief and deal with loss. In addition, 100 providers, social workers, and clergy were surveyed to assess their views of how adults with mental retardation cope and respond during a grief situation. Adults with moderate to severe mental retardation display grief responses similar to all adults: a mixture of sadness, anger, anxiety, confusion, and pain. Individuals continue to experience emotional turmoil 1 year beyond the initial death and personal loss. Caregivers and professionals were mixed on how long a grief reaction continues before it can be viewed as dysfunctional. Intense behaviors, such as self-injury, were noted by respondents in 10-15% of grief reactions. Ability to "feel" or display emotional behavior during grief is not contingent only on a conceptual level. Common reactions include a depressive response (crying, fatigue, sleep disruption, loss of appetite) of moderate intensity. Adults with significant mental retardation verbalized an understanding of the irreversibility of death, and their responses reflect personal beliefs as well. An unknown group of these adults may have been exhibiting a depressive disorder. PMID- 8210609 TI - Cessation of long-term naltrexone therapy and self-injury: a case study. AB - The cessation of long-term Naltrexone administration was investigated through a double-blind, placebo-controlled, withdrawal design in a 28-year-old, profoundly mentally retarded woman with a history of severe self-injurious behavior (SIB). The subject had previously exhibited a dramatic decrease in SIB subsequent to Naltrexone administration. At the end of 1 year of continuous drug treatment, the subject displayed a near-zero rate of SIB episodes. This near-zero rate continued through placebo and no-drug phases of the study and at 6-month (no-drug) follow up. This trend suggests not only that Naltrexone may be effective in reducing SIB, but that long-term administration may produce durable results after treatment cessation. Findings are discussed in relation to the endogenous opioid system theories of SIB. PMID- 8210610 TI - Hypercapnic respiratory failure. PMID- 8210611 TI - Oncogenes and onco-suppressor genes in lung cancer. PMID- 8210612 TI - Airway mucins and their role in defence against micro-organisms. PMID- 8210613 TI - The effect of nicotine and carbon monoxide on exercise performance in normal subjects. AB - In a partially blind randomized control study, nine healthy adult men performed progressive sub-maximal exercise tests, either after chewing nicotine chewing gum (4 mg) or breathing carbon monoxide (320 p.p.m.). Neither agent significantly affected exercise performance, despite a mean rise in blood nicotine to 17.0 ng ml-1 during nicotine administration and a COHb rise to 6.9% whilst breathing carbon monoxide. There was a significant rise in heart rate and blood pressure (P < 0.01) after nicotine administration. The reasons for absence of significant effect on cardiovascular or respiratory performance are discussed. PMID- 8210614 TI - Overnight urine growth hormone, cortisol and adenosine 3' 5' cyclic monophosphate excretion in children with chronic asthma treated with inhaled beclomethasone dipropionate. AB - Overnight urine samples were obtained from 34 asthmatic children, 24 of whom were receiving inhaled beclomethasone dipropionate (BDP), and 30 controls. The urine volume of the children receiving inhaled steroids was significantly greater than that of the other asthmatic children and of the controls (P < 0.05). Urine growth hormone was within the normal range for all of the subjects and there was no demonstrable relationship between urine growth hormone and height or height standard deviation score. Urine steroid output was significantly reduced in the BDP receiving group when the results were expressed in U l-1 but there was no difference between the groups when the results were expressed per specimen. Urine adenosine 3' 5' cyclic monophosphate (cAMP) results were similar for all groups. We conclude that use of BDP increases overnight urine volume but, in our study, does not appear to influence the output of urine cortisol. Urine free cortisol measurements may not be a very sensitive tool for the detection of small changes in endogenous steroid production. The use of BDP does not adversely affect the output of urine growth hormone. PMID- 8210615 TI - Effect of antibiotics on sputum inflammatory contents in acute exacerbations of bronchiectasis. AB - We studied the changes in sputum neutrophil chemotactic activity (NCA) and elastolytic activity (EA) in acute exacerbations of bronchiectasis before and after treatment with oral antibiotics. Twelve patients who chronically produced sputum were assessed in the stable state, and when they subsequently developed symptoms of acute exacerbations, prior to initiation of antibiotics, during 2 weeks of antibiotics, and at 2 and 6 weeks after stopping antibiotics. NCA was measured using modified Boyden's technique with multiwell chemotaxis chamber, and EA with N-succinyl-trialanine-p-nitroanilide as elastase substrate. All 12 patients had NCA (49.3 +/- 8.69% FMLP response) and EA (50.5 +/- 17.1 mU per 100 microliters) in their sputum in the stable state. At acute exacerbation, there was significant increase in NCA (P < 0.001) and EA (P < 0.05). All responded clinically after 1 week of antibiotics, and this was associated with a decrease in NCA and EA back to the levels in stable state. A further week of antibiotics did not result in further decline of NCA or EA. Three patients had another acute exacerbation clinically between 2-6 weeks after stopping antibiotics and their NCA and EA rose again. In the other nine patients, both NCA and EA at 2 and 6 weeks post-treatment were similar to pre-exacerbation levels. Our findings suggest that short course antibiotics effectively control the upsurge in inflammatory activity in acute exacerbations, but has little effect on chronic airway inflammation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210616 TI - Serum androgens and gonadotrophins in bronchial carcinoma. AB - The concentrations of testosterone, free testosterone index derived by two independent techniques (FTI1, FTI2), dehydroepiandrosterone sulphate (DHAS), androstenedione (AND), luteinizing hormone (LH), follicle stimulating hormone (FSH), and sex hormone binding globulin (SHBG) were measured in 38 healthy male controls aged between 40 and 60 years (Group 1) and in 52 male patients with bronchial carcinoma of whom 28 were aged between 40 and 60 years (Group 2) and 24 were aged over 60 years (Group 3). Compared with Group 1, testosterone, FTI1, FTI2, and DHAS were significantly lower (P < 0.001), AND and LH were significantly higher (P < 0.001) and there was no significant difference in FSH or SHBG, in Group 2. No significant difference between Groups 2 and 3 was found for any variable. Analysis of covariance for Groups 2 and 3 combined, showed testosterone, FTI1 and FTI2 were significantly lower in the presence of metastases. These results suggest a more widespread abnormality of androgen metabolism in male patients with bronchial carcinoma than a simple reduction in serum testosterone; DHAS is also significantly reduced while AND is significantly increased. The primary abnormality appears to be at testicular and/or adrenal level as pituitary function appears normal as witnessed by compensatory increases in LH. PMID- 8210617 TI - Lung deposition from four nebulizers. AB - The total and regional deposition of aerosol has been compared using four nebulizers; the Pari Boy 37.80, Pari IS-2, RespirGard II and Penta-Sonic. The aerosol was radiolabelled with [99Tcm]DTPA, administered to ten healthy subjects and the distributions monitored by gamma scintigraphy. Median lung aerosol depositions expressed as percentages of the doses initially loaded into the nebulizers were: Pari IS-2 19%, Pari Boy 37.80 13%, RespirGard II 9% and Penta Sonic 2%. The ratios of the peripheral to central lung deposition, however, were greater with the RespirGard II and Penta-Sonic nebulizers. The choice of the most appropriate nebulizer depends on the pharmaceutical being administered, since aerosol must be delivered to the required site in sufficient quantity, whilst minimizing the incidence of local or systemic side-effects. PMID- 8210618 TI - Primary intrathoracic tumours in children--a review of 11 cases. PMID- 8210619 TI - Primary clear-cell carcinoma of the lung. PMID- 8210620 TI - Transbronchial needle aspiration in the diagnosis of pulmonary sclerosing haemangioma. PMID- 8210621 TI - [Thrombolytic therapy]. PMID- 8210622 TI - [Good health. The results of a study (II)]. PMID- 8210623 TI - Further considerations on the changing face of pneumonia in Marche Region (central Adriatic coast of Italy). AB - The present paper provides a more detailed review of some themes already discussed in previous papers concerning the changing face of pneumonia in an area of the central Adriatic coast of Italy, including an ex novo examination of the correlations between radiological findings and serological groups not previously reported. The discussion concentrates particularly on some questions raised by the research, such as the apparent rarity of pneumococcus, the elevated number of seronegatives appearing as atypical pneumonia, the high percentage of "bacterial type" cases occurring among the viral-like, and the therapeutic problem. PMID- 8210624 TI - [Plasma fibronectin in chronic liver diseases]. AB - This study was carried out to evaluated the role of the fibronectin (FN) in chronic liver diseases. For these reasons FN plasmatic concentration was assayed in patient with different degrees of chronic liver disease. For these reasons FN plasmatic concentration was assayed in patient with different degrees of chronic liver disease; the correlation between FN and the most common parameters of liver function was also evaluated. Moreover we also correlated FN plasma levels with laminin and the N-terminale peptide of type III procollagen, serum levels, that are through to be markers of fibrogenesis. 172 patients were studied: twenty-one patients suffering from chronic persistent hepatitis (CPH), 45 from chronic active hepatitis (CAH) and 106 from liver cirrhosis (LC). Last patients were also divided according the Child-Pugh's classification. Control group was composed of 74 healthy blood donors. Significant reduction of plasmatic levels of FN was found in the LC groups in comparison with control group (p < 0.0001) and also with CPH group (p < 0.01) and with CAH group (p < 0.0001). Lower values of FN were found in the LC group at advanced stage (Child-Pugh's B and C classes). In the group of CAH significant correlations with the parameters of cholestasis (GGT, APh, Tot. Bil. p < 0.005) were found, while in the group of LC significant correlations both with the parameters of synthesis (Alb. and Protr. time p < 0.01) and necrosis (AST/ALT p < 0.001). A negative correlation was also found between FN and spleen volume (p < 0.05). No correlation between FN and the parameters of fibrosis was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210625 TI - [Thrombolytic therapy after prolonged cardiorespiratory resuscitation in acute myocardial infarct with primary ventricular fibrillation]. AB - Treatment of acute myocardial infarction with intravenous thrombolytic agents improves survival and limits the infarct's size. Despite its proved efficacy, thrombolytic therapy is currently used for only a minority of patients with acute myocardial infarction. Because of the possibility of significant haemorrhagic complications, certain groups of patients traditionally have been excluded from receiving this therapy. Patients with acute myocardial infarction following prolonged cardiopulmonary resuscitation are often considered ineligible for thrombolytic therapy, because an higher bleeding risk. The Authors report the case of a 52 yr old man with primary ventricular fibrillation and acute myocardial infarction treated with streptokinase i.v. after having a prolonged (20 min.) cardiopulmonary resuscitation. The patient did not report gross trauma and recovered to a completely functional status without any relevant bleeding complication. To date, only few case reports exist on thrombolysis in patients with recent prolonged resuscitation, and most of them are favourable. The literature on thrombolytic therapy in acute myocardial infarction following cardiopulmonary resuscitation is reviewed. Recent (< 2 w) prolonged (< 1 min.) cardiopulmonary resuscitation, per se, should not be regarded as absolute contraindication for thrombolytic therapy in patients with acute myocardial infarction if gross trauma and oldest age are absent. Prospective controlled studies are necessary to remove definitively this contraindication for thrombolysis. PMID- 8210626 TI - [The MR imaging of intracardiac masses]. PMID- 8210627 TI - [New horizons in medicine. The attractors]. AB - The discovery of the fact that chaotic systems can suddenly coagulate into deterministic systems, and that deterministic systems can precipitate into chaotic systems has, on the one hand, clearly revealed the limits of the Cartesian geometrization of random phenomena, and on the other, has made in possible to identify the attractor as the reference entity when studying the functional dynamics of biological systems. The attractors is identified as the point of equilibrium upon which the behaviour of a dynamic system stabilizes and towards which it is constantly attracted. In some systems the attractor is identified as an "ideal" optimum reference point termed "the point". In other systems, however, the attractor is identified as a closed curve: "the ultimate cycle". Lastly, in other systems the attractor is identified as a surface in which the space of the states delimits a flat doughnut-shaped image constituting a "torus". The recent discovery of the laws governing deterministic chaos has made it possible to identify a new type of attractor termed the "strange attractor". This attractor has a fractal dimension (i.e. one midway between linear and plane), is of finite dimension and depends on the initial condition of the system. In many biological functions it is now possible to demonstrate the presence of attractors that operate starting from different initial conditions or that vary with time or that display both these conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210628 TI - Anaemias and other haematological changes due to disease of the alimentary tract. AB - Often anaemia and other haematological changes are unrelated to primary diseases of the erythron but are secondary to gastrointestinal alterations, such as occult or overt blood loss or defective absorption of essential haemopoietic factors. This overview emphasizes, through the description of different pathological conditions, the fundamental role of the gastrointestinal tract in maintaining a normal haematological balance. This role is jeopardized in diseases related to the liver and to the various sections of the alimentary tract from the oesophagus to the rectum. Of primary importance in inducing haematological changes which may be modified by curing the primary condition are essentially the diseases of the small intestine, following malabsorption of iron, folic acid and vitamin B12, such as conditions associated with small intestine bacterial overgrowth, tropical sprue, gluten sensitive enteropathy whipple's disease and various infections with intestinal parasites. Moreover, the Authors briefly survey the other pathological conditions of the alimentary tract often associated with chronic bleeding. In this context of particular relevance are the screening procedures which may reveal the presence of occult bleeding caused by neoplastic diseases. It is important that the clinician be aware of this possibility and of the underlying physiopathological mechanism of the diseases of the alimentary tract, so that appropriate and timely therapeutic measures may be undertaken. PMID- 8210630 TI - Differentiation of physiological and malignant cells of the B-cell system. PMID- 8210629 TI - [The enzymatic mechanisms involved in the pathogenesis of rheumatoid arthritis and arthrosis. The role of metalloproteases and serine proteases in the breakdown of articular cartilage]. AB - Rheumatoid arthritis and osteoarthritis, expression, respectively, of inflammatory and degenerative articular involvement, are the most important diseases affecting joint cartilage. Proteolytic enzymes are the effectors of the articular damage: their increased production by chondrocytes and synoviocytes leads to cartilage breakdown. These enzymes, whose structure and specific activities have been defined in the recent years, carry out their action in the extracellular matrix. They are characterized by the presence of a particular element at the active site, that allows to distinguish four different families. The most studied and the best known among them are metalloproteinases, represented by several enzymes with common features, and serinoproteinases, some members of which, particularly urokinase and tissue-type plasminogen activator, are recently indicated as potential responsible for articular destruction. Activators, and inhibitors of proteinases play a fundamental role: a fine balance, that controls the mechanisms of activation and inhibition, seems to take place at transcriptional level. Any factor able to modify the cellular shape and the cytoskeleton, gives rise to lytic enzyme expression at the genomic level. With the progress of knowledges, serinoproteinases are assuming an increasing relevance, particularly the components of the fibrinolytic pathway. PMID- 8210631 TI - Cytogenetic abnormalities associated with childhood acute myeloblastic leukemia. PMID- 8210632 TI - DNA aneuploidy in childhood acute lymphoblastic leukemia: relation to clinical determinants and prognosis within four consecutive BFM trials. PMID- 8210633 TI - Clinical significance of cytogenetic studies in childhood acute lymphoblastic leukemia: experience of the BFM trials. PMID- 8210634 TI - Chromosomal abnormalities in adult acute lymphoblastic leukemia: results of the German ALL/AUL Study Group. PMID- 8210635 TI - Molecular genetic techniques for detection of minimal residual disease in acute lymphoblastic leukemia: possibilities and limitations. PMID- 8210636 TI - Immunophenotypic and immunogenotypic detection of minimal residual disease in acute lymphoblastic leukemia. PMID- 8210637 TI - Detection of aberrant antigen expression in acute myeloid leukemia by multiparameter flow cytometry. PMID- 8210638 TI - Normal and aberrant T-cell receptor protein expression in T-cell acute lymphoblastic leukemia. PMID- 8210639 TI - Detection of residual leukemic cells in adult acute lymphoblastic leukemia by analysis of gene rearrangements and correlation with early relapses. PMID- 8210640 TI - Interleukin-2-based immunotherapy in the management of minimal residual disease in acute leukemia patients. PMID- 8210641 TI - Preclinical studies of T-cell-mediated immune responses against autologous tumor cells in patients with acute leukemia. PMID- 8210642 TI - Susceptibility of human leukemia cells to allogeneic and autologous lymphokine activated killer cells and its augmentation by exposure of leukemia target cells to cytotoxic drugs in vitro and in vivo. PMID- 8210643 TI - Regulation of protooncogenes and cytokine genes in acute lymphoblastic leukemia. PMID- 8210644 TI - Cellular drug sensitivity of immunophenotypic subgroups of childhood acute lymphoblastic leukemia. PMID- 8210645 TI - Use of clinical and laboratory features to define prognostic subgroups in B precursor acute lymphoblastic leukemia: experience of the Pediatric Oncology Group. PMID- 8210646 TI - Incidence and prognostic significance of immunophenotypic subgroups in childhood acute lymphoblastic leukemia: experience of the BFM study 86. PMID- 8210647 TI - Incidence, clinical and laboratory features, and prognostic significance of immunophenotypic subgroups in acute lymphoblastic leukemia: the GEIL experience. PMID- 8210648 TI - Incidence and prognostic significance of immunophenotypic subgroups in childhood acute lymphoblastic leukemia: the experience of the AIEOP Cooperative Study. Associazione Italiana Ematologia Oncologia Pediatrica. PMID- 8210649 TI - Mutations in the regulatory domains of bcr/abl-positive leukemias detected by solid-phase automated DNA sequencing. PMID- 8210650 TI - Flow cytometric analysis of intracellular myeloperoxidase and lactoferrin in leukemia diagnosis. PMID- 8210651 TI - Clonal analysis of n-ras gene activation in acute myeloid leukemia. PMID- 8210652 TI - Morphologic basis for the MIC classification in acute myeloid leukemia. PMID- 8210653 TI - Molecular genetics of the t(15;17) translocation in acute promyelocytic leukemia. PMID- 8210654 TI - Immunophenotype of hematologic neoplasms with a translocation t(8;21). PMID- 8210655 TI - Diagnostic and prognostic importance of immunophenotyping in adults with acute myeloid leukemia. PMID- 8210656 TI - Immunophenotype of acute myeloid leukemia: correlation with morphological characteristics and therapy response. PMID- 8210657 TI - Multiparameter analysis of blast cells in patients with acute leukemia following a primary myelodysplastic syndrome. PMID- 8210658 TI - Immunological, ultrastructural and molecular features of unclassifiable acute leukaemia. PMID- 8210659 TI - Incidence and clinical relevance of myeloid antigen-positive acute lymphoblastic leukemia. PMID- 8210660 TI - Myeloid-associated antigen expression in childhood acute lymphoblastic leukemia. Austrian Pediatric Oncology Group. PMID- 8210661 TI - Contribution of electron microscopy to the classification of minimally differentiated acute leukemias in children. PMID- 8210662 TI - Molecular cytogenetic applications in leukemias. PMID- 8210663 TI - Expression of B-cell-associated antigens during B-cell ontogeny. PMID- 8210664 TI - [Psychoses and driving fitness--development of criteria for clinical assessment]. AB - The legal foundations for driver fitness evaluation in psychiatric conditions are enumerated in the 1985 "Illness and road traffic" expert opinion of the advisory medical council with the Federal Ministry of Transport. In case of the endogenous psychoses, in-patient episodes will invariably give rise to a call for expert psychiatric appraisement, notwithstanding the fact that reliable and valid criteria, with the exception of a standardized driving sample, continue to be almost non-existent. Carried out between 1989 and 1991 with support from the Federal Employment Institute in the framework of an employment creation project as well as from Bundesanstalt fur Strassenwesen, the present study hence had been aimed at correlation-statistical identification of as valid driving ability predictors as possible in post-acute patients with a diagnosis of schizophrenic psychosis (ICD 295.3). The patients' pre-discharge fitness for driving, for one, was assessed using a number of psychological procedures and, for the other, was examined during a 60 minute practical driving sample, involving both city and autobahn driving. Driving behaviour during the practical trial was taken down according to pertinent categories, with subsequent judgment of overall driving performance both by self-ratings and by driving instructor ratings by means of a school grades scale of 1 to 6. With reference to pertinent studies elsewhere, our test battery had consisted of procedures for testing visual perception, reaction, selective and split attention, personality structure, anxiety, and risk taking.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210665 TI - [Methodological-didactic concepts in the occupational rehabilitation of adults in Phase II facilities?]. AB - While specific methods from disabled and special education didactics are available for young people, pertinent didactical concepts and experience are lacking in case of adults, in particular for rehabilitees with chronic mental illness and brain damage. Further education schemes have hence been started in 1989 within the Federal working group of medical-vocational (phase II) facilities, focussing on appropriate learning strategies and on rooting them in the minds of educators and teachers. Oriented along the "Berlin didactical model", Stadler's approach is considered fundamental in developing a didactical concept for adults with disabilities. Practical suggestions and hints at existing, proven methodical strategies are used to help illustrate concrete possibilities for systematically gearing time-tested methodical strategies to disability-generated learning problems. An almost synchronous development, similar learning strategies are to be found in industrial and occupational didactics as well, under a "holistic education" and "enhancement of key qualifications" heading. Participant orientation as the fundamental principle of a "disability-specific" methodology, holistic didactic concepts, a fitting learning organization, application of project-, activity- and experience-based methods, fitting problem-solving techniques, as well as a reconsideration of current teaching principles, are in the foreground of the present contribution. PMID- 8210666 TI - [Results in extramural rehabilitation of chronic mental patients: 5-year follow up study]. AB - Presented are the findings of a 5-year prospective study concerning residential rehabilitation of 53 subjects with chronic mental illness living in a differentiated system of complementary facilities and services. The focus had been the chronically ill patients' development and disease course, as reflected in their psychological wellbeing, work status, therapeutic requirements, social contacts, as well as periods of rehospitalization. At the end of the 5-year period, 50% of the subjects were living in sheltered communal groups, and some 25% fully on their own. Only 10 percent had returned to psychiatric hospitals as long-term patients. Vocational integration in the general labour market is only rarely achieved, but the work available in sheltered employment is suitable for 40%. All of the patients were in medical care after 5 years. Given a differentiated system of complementary support and services in the residential and vocational spheres, for medical care and leisure activities, persons with chronic mental illness, too, are able to live outside the psychiatric hospital, above all enjoying greater normality in their lifestyles as well as a higher degree of personal autonomy. PMID- 8210667 TI - [Quality of life and coping in the comparison of various groups of chronic illness during inpatient rehabilitation]. AB - The concept of adaptation and quality of life has gained central importance in the research on chronically ill patients and their rehabilitation. This contribution examines the impact of psychological and behavioural factors on the quality of life and coping processes in two groups of chronically ill patients (i.e., n = 48 myocardial infarction survivors, and n = 48 patients with liver diseases). Coping responses and quality of life were measured using Janke et al.'s stress coping questionnaire SVF (1985), while other variables (psychosocial stress and social support) were determined by a variety of self-report data, test measures (von Zerssen's emotional state scale, 1976), as well as interview data, with repeat data compilation after three years (longitudinal study). Significant differences were found for each of the patient groups. Effectiveness of coping appeared to be negatively linked with frequent use of "avoidance", "denial", and "resignation" in patients with psychosocial strain and lack of information. The choice of coping strategy seems to be multi-determined and is related to illness state and sex, with changes occurring over time. The knowledge of coping strategy preferences is highly relevant for the relationship between physician and patient as well as for the process of rehabilitation. PMID- 8210668 TI - [The course of inpatient rehabilitation in gastrointestinal and metabolic diseases under increasing integration of behavior and experience]. AB - Starting out from the thesis that behaviour and felt experience, i.e., the patient's "subjective world", have considerable influence on chronic diseases and their consequences in the gastrointestinal field, a "basic course documentation" based comparison has been carried out of the courses of 4-week in-patient rehabilitation programmes designed to increasingly incorporate interventions directed at this area; the study population had consisted of two groups of patients (n = 688 each) without any significant differences concerning age and sex distribution admitted during the summer terms of 1990 (Group A) and 1991 (Group B), respectively. This documentation (in DBASE IV format) compiles (anonymized) patient data at an "objective" level on the one hand, i.e. basic data (such as diagnoses, age, sex), results obtained by the Edinburgh Rehabilitation Status Scale (ERSS), risk behaviour, and scope of interventions both in the organ-medical and physical therapy fields and in the area of "instruction, motivation, support, group work, and creativity" (designed to achieve integration of behaviour and felt experience); on the other hand, at "subjective level", it comprises the patient's own judgements relative to the treatment regimen and its environment, with subsequent correlational analysis of the data obtained (using the SPSSPC statistical package). As had been expected, correlations have on the one hand been stated at the "objective" level between an increased share of more "serious" conditions (ICD) in 1990 as compared to 1991 and higher ERSS scores (i.e., increased impact of disease consequences), greater organ-medical care intensity, and frequency of incapacity for work; on the other hand, at "subjective" level, strong linkages were found among the item ratings for general sense of improvement, specific and general therapy, as well as so called "therapeutic environment". When the two levels are linked, the sense of improvement, as expected, is found to correlate negatively with the ERSS, but positively with the scope of the interventions designed to foster integration of behaviour and felt experience. The judgements given for quality of care provided relative to the patient's self-reported primary disorder and for general medical care correlate positively both with the scope of diagnostic/therapeutic organ medical interventions and integration-focussed ones, which, at least from the patient's perspective, hence exercise an ascertainable, essential effect in the therapeutic setting of in-patient rehabilitation in gastrointestinal and metabolic diseases. PMID- 8210669 TI - [Professionalization in the field of psychiatric vocational rehabilitation]. AB - In this contribution the issue of professionalization is being discussed, mainly tailored to the field of vocational rehabilitation in Dutch Mental Health. Presented is an overview of existing routines frequently used in the methodical actions of industrial therapists and occupational therapists. Several important methodical suggestions for the concretization of a renewed concept of vocational rehabilitation were formulated. The last part of the contribution explores the key-question: "Professionalization?" PMID- 8210670 TI - [Disability-related rehabilitation program exemplified by the working tools of the Federal Rehabilitation Council]. AB - The social right of disabled persons to comprehensive integration assistance calls for dovetailing the benefits and services of the structured rehabilitation system in such a way that the disabled person's overall need is matched by equally comprehensive assistance. In those involved in rehabilitation, this goal presupposes adequate information concerning the various disabilities and rehabilitation objectives, as well as the course of the rehabilitation process proper. The Working Aids published by the Federal Rehabilitation Council (Bundesarbeitsgemeinschaft fur Rehabilitation) provide a state-of-the-art outline of rehabilitation in the most significant disabilities, including hints and recommendations relative to medical, psychological, psychosocial and vocational rehabilitation aspects. They underscore the need for interdisciplinary action among the professions as well as for close cooperation of the rehabilitation agencies involved, and impart the knowledge needed to be able to identify and bridge the interfaces and transitions in the course of rehabilitation. PMID- 8210671 TI - [Vocational rehabilitation of women--seminar of the BAR (Federal Rehabilitation Council) on May 18-19, 1993 in Kassel]. PMID- 8210672 TI - [Status of rehabilitation and physical medicine in Latvia. Impressions of a trip and an international physicians' meeting in June 1993 in Riga]. PMID- 8210673 TI - A bacterial periplasmic receptor homologue with catalytic activity: cyclohexadienyl dehydratase of Pseudomonas aeruginosa is homologous to receptors specific for polar amino acids. PMID- 8210674 TI - Studies on the large subunit ribosomal RNA genes and intergenic spacer regions of non-proteolytic Clostridium botulinum types B, E and F. AB - The large-subunit ribosomal ribonucleic acid (23S rRNA) genes of non-proteolytic (group II) strains of Clostridium botulinum toxin types B, E and F were amplified using the polymerase chain reaction (PCR), and cloned in Escherichia coli. Sequence determination showed that the 23S rRNA genes were 2910 nucleotides in length, and comparative analysis revealed approximately 99.5% sequence similarity. The 23S rRNA gene sequence of a strain phenotypically resembling non proteolytic C. botulinum, except in not producing botulinal neurotoxin, was also determined and displayed 99.5% sequence similarity with those from toxigenic strains. A diagnostic sequence within the 23S rRNA characteristic for non proteolytic C. botulinum was identified and used for the design of an oligonucleotide probe. Molecular hybridizations with PCR-amplified rDNA targets provided a precise and reliable method of identifying non-proteolytic (or Group II) C. botulinum and closely related non-toxigenic strains. PMID- 8210675 TI - Presence of mrr- and mcr-like restriction systems in coryneform bacteria. AB - Efficient transformation of Brevibacterium flavum MJ233C and Corynebacterium glutamicum ATCC 31831 (up to 5.0 x 10(7) transformants/microgram DNA) depends on the source of plasmid DNA. The transformation efficiencies of B. flavum MJ233C and C. glutamicum ATCC 31831 increased nearly 10(3)-fold when plasmid DNA was isolated from the recipient strain itself or from a damdcm Escherichia coli mutant, as compared with DNA passed through a modification-proficient E. coli strain. These results suggest the presence of a methyl-specific restriction system in certain strains of coryneform bacteria. In addition, electroporation conditions were optimized. PMID- 8210676 TI - The histidine operon of Azospirillum brasilense: organization, nucleotide sequence and functional analysis. AB - A 3457-base pair fragment of Azospirillum brasilense DNA which complemented mutations in the hisA and hisF genes of Escherichia coli was sequenced. The sequence analysis revealed the presence of six major contiguous open reading frames (ORF). The comparison of the predicted amino acid sequence of these ORF with those encoded by the eubacterial, archaebacterial and eukaryotic his genes sequenced thus far revealed that four of them have a significant degree of homology with the E. coli hisH, hisA, hisF and the C-terminal domain of the hisI gene products. S1 mapping experiments indicated that the putative transcription start site coincided with the AUG translational initiation codon of the hisBd gene, the first gene of the A. brasilense his operon. Downstream from the last ORF, a sequence was identified which functions as a Rho-independent transcription terminator. Comparison of amino acid sequences, gene order and organization and evolutionary aspects of the A. brasilense his cluster are discussed. PMID- 8210677 TI - Release of lipopolysaccharide during Bordetella pertussis growth. AB - The effect of the addition of (2,6-O-dimethyl)-beta-cyclodextrin (Me beta CD) during growth of Bordetella pertussis in synthetic Stainer-Scholte liquid medium (SS) on lipopolysaccharide (LPS; endotoxin) release was investigated. The Me beta CD concentration used (3 mg/ml) was chosen according to the optimal level found in previous studies to enhance major soluble antigen production. The profiles in SDS-PAGE (sodium dodecyl sulphate/polyacrylamide gel electrophoresis) of LPS extracted from cells grown in SS and SS + Me beta CD media revealed similar patterns. Although the LPS content of whole cells decreased during cell growth, yields obtained at different growth periods in cyclodextrin medium were lower than those corresponding to SS medium alone. Consequently, the level of LPS released in supernatants of both media increased during cellular growth. This amount of free LPS was higher in the cyclodextrin liquid medium and became significant at the beginning of the stationary growth phase. Binding of cyclodextrin to pertussis cells could account for the data obtained. Similar results were obtained with all species of the genus Bordetella. PMID- 8210678 TI - Polymerase chain reaction with the 30-kb circular plasmid of Borrelia burgdorferi B31 as a target for detection of the Lyme borreliosis agents in cerebrospinal fluid. AB - The polymerase chain reaction (PCR) was developed for use in the detection of Borrelia burgdorferi sensu lato, the Lyme disease agent. A 333-bp fragment of the 30-kbp circular plasmid from Borrelia burgdorferi B31 was amplified and PCR products were analysed by DNA-DNA hybridization. Sensitivity was enhanced by addition of a carrier to the samples before treatment and enabled detection of as few as 1 to 10 bacteria. Specific products were obtained only with the Lyme disease agents, but not with other spirochetes or unrelated bacteria. B. burgdorferi sensu lato was detected in cerebrospinal fluid (CSF) from 11 out of 45 patients with confirmed Lyme neuroborreliosis. In a prospective study, 20 out of 315 CSF samples from potential patients were PCR-positive. Forty uninfected patients were PCR-negative. PMID- 8210679 TI - Distinctive electrophoretic pattern of esterases produced by Alcaligenes species. AB - The esterases produced by 34 strains of Alcaligenes faecalis, 16 strains of A. denitrificans subsp. xylosoxydans, 5 strains of A. piechaudii and 10 strains of A. denitrificans subsp. denitrificans were analysed by horizontal polyacrylamide agarose gel electrophoresis. These enzymes were distinguished by their spectra of hydrolytic activity towards 5 synthetic substrates (hydrolytic type) and their electrophoretic mobilities (electrophoretic type). Four hydrolytic types of esterases were produced by A. faecalis, three hydrolytic types by A. denitrificans subsp. xylosoxydans, three hydrolytic types by A. piechaudii and 14 hydrolytic types by A. denitrificans subsp. denitrificans. Both (hydrolytic and electrophoretic) properties and the pattern of esterases produced by each strain were used to define 8 zymotypes in A. faecalis, 6 zymotypes in A. denitrificans subsp. xylosoxydans, 3 zymotypes in Alcaligenes piechaudii and 10 zymotypes in Alcaligenes denitrificans subsp. denitrificans. These results permit precise identification of strains within the four species of Alcaligenes and provide useful epidemiological markers. PMID- 8210680 TI - Evaluation of the use of 5-mycoloyl-beta-arabinofuranosyl-(1-->2)-5-mycoloyl- alpha-arabinofuranosyl-(1-->1')-glycerol in serodiagnosis of Mycobacterium avium intracellulare complex infection. AB - 5-Mycoloyl-beta-arabinofuranosyl-(1-->2)-5-mycoloyl-alpha-ar abinofuranosyl-(1- >1')-glycerol, an antigenic glycolipid from the Mycobacterium avium intracellulare complex (MAC) was examined for its applicability to the serodiagnosis of MAC infection by ELISA. Serum IgM antibody titres against this glycolipid in healthy controls, pulmonary tuberculosis patients and sputum-MAC culture-negative MAC patients were generally below the cut-off point (ELISA negative), whereas most of the MAC-culture-positive MAC patient sera were ELISA positive (93.5%) and their titres were often very high. Thus, high serum IgM titres against this glycolipid may be said to imply that the MAC disease is in an active phase. PMID- 8210681 TI - Development of a phage typing system for Staphylococcus hyicus. AB - Bacteriophages were released by 98% of 100 Staphylococcus hyicus strains studied after treatment with mitomycin C. Twenty-three phages with different lytic spectra were included in a phage typing system and used for typing S. hyicus. On a test-set of 100 epidemiologically unrelated S. hyicus strains isolated from Danish pig herds, the phages were able to type 92% of the strains, producing 16 different phage types. Reproducibility of the phage typing system after subculture of the strains and using fresh phage stock was 96%. Typability ranged from 52 to 80% when typing porcine strains originating from other countries. Although phages were isolated from porcine skin strains exclusively, the system produced phage types in S. hyicus strains of bovine origin. Ten strains of S. aureus and S. chromogens were not typable by these phages. Strains belonging to one phage type (A/B/C/W) were isolated significantly more often from piglets with exudative epidermidis than from healthy piglets. The phage typing system described appears to be a valuable tool in diagnosis of exudative epidermidis in pigs, and furthermore, might be of value in epidemiological studies of S. hyicus. PMID- 8210682 TI - The effect of indomethacin and reserpine on renal vascular escape. AB - Isolated rabbit kidneys were perfused with Krebs-Henseleit solution in an open system designed to allow study of dose-response relationships. The effects of the cyclooxygenase inhibitor indomethacin and of reserpine on (norepinephrine) noradrenaline (NOR)-induced renal vascular escape were studied. Indomethacin (50 mg/Kg) was given two hours prior to surgery followed by continuous infusion (0.33 mg/min), and blocked renal vascular escape in all doses of NOR tested (10(-7)-10( 4) M) by 70-80%. Reserpine (10 mg/Kg, given 10-12 hours prior to organ perfusion), also suppressed renal vascular escape significantly by 80-90%. We conclude that there is a participation of prostaglandins in noradrenaline induced escape in the perfused rabbit kidney. PMID- 8210683 TI - Pharmacodynamic interaction of clonidine and muscimol in hypertension. AB - The effect of the GABA agonist muscimol on the hypotensive action of clonidine in SHR was investigated. Muscimol administered before clonidine significantly (p < 0.01) intensified clonidine-induced reduction of blood pressure. This effect was achieved at muscimol doses which themselves had no influence on blood pressure. Muscimol injected after clonidine was ineffective. Our data suggest that the muscimol-clonidine interaction occurs at the level of GABAergic neurotransmission since both agents have been proved to activate the function of GABAergic neurons. PMID- 8210685 TI - Formation of fatty acid propyl esters in liver, lung and pancreas of rats administered 1-propanol. AB - The esterification of fatty acids by ethanol has been associated with a number of adverse reactions. In this study, the administration of 1-propanol (3 ml/kg 24 and 12 hours prior to measurements) to rats resulted in the formation of fatty acid propyl esters of oleic acid, lauric acid and to a lesser extent, palmitic acid and myristic acid. Formation was highest in liver and pancreas and was lower in lung. PMID- 8210684 TI - Action of estrogen and adrenocorticoids on adenocarcinoma induction by 1,2 dimethylhydrazine in male rats. AB - Groups of male Sprague-Dawley rats at 39 days of age, were injected s.c. with estradiol benzoate (15 micrograms/kg), cortisone acetate (2.5 mg/kg) and deoxycorticosterone acetate (10.0 mg/kg) in peanut oil, the controls receiving the oil vehicle on days 1 and 3 and weekly thereafter for a total of 32 injections. 1,2-Dimethylhydrazine was administered s.c. weekly after the 1st 2 drug doses, the dosage as base being 9.0 mg/kg for the 1st 7 injections, then 19.4 mg/kg for the last 13 dosages. The rats were killed 31 weeks after the 1st DMH injection. The changes in animal condition at necropsy were moderate to extreme in half of the rats and all survived the 20 DMH injection-schedule; mortality was low per group but elevated with the deoxycorticosterone acetate treatment (40%). Essentially all rats displayed colon adenocarcinomas and the total frequency and the number in the proximal and distal portions were in the control ranges except for the statistically significant decrements in overall and distal colon numbers for the estrogen-treated group and possibly, near significance in case of the cortisone acetate-injected rats. Small intestinal adenocarcinomas which were more prevalent in the upper areas occurred among the groups. As based on the current findings with estrogen, the trend was in the direction of an inhibiting effect on DMH tumorigenesis in contrast to a stimulatory response reported for androgenized males. PMID- 8210686 TI - Brain energy metabolites in mice after an acute exposure to carbon monoxide. AB - Brain energy metabolites were determined in mice over 8 days after an acute exposure to carbon monoxide (CO). The exposure of 0.5% CO for 15 min caused 33% mortality. Survived mice recovered completely within 30 min in room air. Lactate increased markedly immediately after the exposure, while glucose increased 30 min later. Four hours, 1 day, 4 days and 8 days after the exposure, the levels of brain energy metabolites including phosphocreatine and ATP did not differ from those of the control. Thus, energy metabolism in the whole brain in mice appears not to be impaired after they survive an acute CO intoxication. PMID- 8210687 TI - Nandrolone decanoate reduces the premature mortality of cardiomyopathic hamsters. AB - Male hamsters of an inbred strain carrying a genetic trait for cardiomyopathy were dosed by sc injection weekly with an anabolic-androgenic steroid, nandrolone decanoate, beginning when 3 months old. Two groups (N = 17) received doses of 2 and 4 mg per animal, while a vehicle control group received an equal volume of sesame oil. Rather than a hypothesized shortening of longevity, the steroid treatment significantly prolonged survival of the hamsters, which ordinarily die of congestive heart failure. At the median time to death for controls (355 days of age, 257 days of treatment), the steroid groups had mortality of only 2/17 and 4/17 (vs. 9/17, p < 0.01). PMID- 8210688 TI - Effect of glutathione monoethyl ester on glutathione level and cardiac energetics in reperfused pig heart. AB - The GSH level in myocardial tissue represents an important defense mechanism against oxygen toxicity. Since the ischemia-induced depletion of GSH might favour the cytotoxicity of oxygen-derived free radicals produced during reperfusion, we assessed the effects of the GSH donor, glutathione monoethylester, in anaesthetized pigs subjected to 90 minutes of coronary occlusion followed by 30 minutes reperfusion. The drug was infused intracoronarily at a dose of 1 mg/ml (0.5 ml/min) throughout the experimental period. After coronary occlusion and reperfusion, we found a decrease in GSH, ADP, ATP and phosphocreatine levels in reperfused compared with non-ischemic tissue. Less evident were the differences in mitochondrial function, there being only a reduction in the reperfused tissue of the respiratory control index and state 3 respiration values when pyruvate was used as substrate. The infusion with glutathione monoethylester decreased the depletion of tissue GSH and improved the GSH/GSSG ratio, particularly in the non ischemic tissue. Moreover, the drug decreased the mitochondrial dysfunction at the level of pyruvate utilization and partially prevented the fall in ATP in the reperfused tissue. This study confirms a possible protective effect of glutathione monoethylester in the prevention of reperfusion-induced myocardial damage. PMID- 8210689 TI - Decrease in biliary excretion of copper in Long-Evans cinnamon (LEC) rats causing spontaneous hepatitis due to a gross accumulation of hepatic copper. AB - The concentration of biliary Cu was 0.12 +/- 0.01 microgram/ml in male LEC rats aged 14 weeks and 0.43 +/- 0.09 micrograms/ml in Fischer rats of the same age. When copper chloride (170 micrograms/kg b.w. as Cu) was infused intravenously (i.v.), the concentration of biliary Cu increased to only 0.21 +/- 0.06 microgram/ml 30 min after the infusion in LEC rats. In contrast, Fischer rats showed a concentration about 10 times higher (4.02 +/- 2.2 micrograms/ml) than that before the infusion. In Fischer rats pretreated with cadmium chloride, the biliary Cu concentration was 1.04 + 0.43 micrograms/ml 30 min after infusion of copper. Horseradish peroxidase (E.C.1.11.1.7) infused iv along with copper chloride was excreted into bile at a low level in LEC rats compared to Fischer rats. Our results suggest that the gross accumulation of hepatic Cu in the new, mutant LEC rats is due to a low excretion of Cu into bile and that the hepatobiliary dysfunction is related to spontaneous hepatitis. PMID- 8210690 TI - Fluoride absorption from disodium and calcium monofluorophosphates from the gastrointestinal tract of rats. AB - The contribution of the stomach and the small intestine to the in vivo absorption of fluoride from disodium and calcium monofluorophosphates was studied in comparison with that observed when sodium fluoride is given to rats. In vitro experiments with ligated duodena were also carried out. Fasted rats were given orally 50 micrograms of fluoride in pH 6.3 buffered disodium monofluorophosphate solutions with and without 50 mM added calcium. The same amount of fluoride was administered in the form of an aqueous sodium fluoride solution. In both cases the fluoride solutions contained trace amounts of (14C)-labeled polyethyleneglycol as a marker for the study of water movement through the gastrointestinal tract. Results obtained show the small intestine as the main site of the absorption of the studied compounds. Under the fasting conditions employed in our study gastric absorption was in turn, almost negligible. While fluoride transport from sodium fluoride seems to occur through a difussion mechanism, disodium and calcium monofluorophosphates appear to be absorbed through a more complex mechanism involving an enzymatic hydrolysis and an independent and possibly parallel direct tissue absorption of a soluble, neutral calcium monofluorophosphate complex. PMID- 8210691 TI - Evidence that diazepam elicits alterations on rat renal function. AB - The effects of diazepam on rat renal function were investigated by means of clearance techniques in conscious animals. Different intravenous doses of diazepam were tested: 0.1, 0.3 and 10 mg/Kg body weight A marked increase in fractional water, sodium and potassium excretion was found in every group studied. This alteration was associated with a urine-to-plasma osmolality ratio diminution. On the other hand, no modifications in glomerular filtration rate or p-aminohippuric acid clearance were observed. The reabsorption of water in collecting tubule in diazepam treated rats was decreased as compared with control rats. To assess diazepam-effects on collecting tubule response to vasopressin, the effects of desmopressin on concentrating ability in control and diazepam treated rats were tested. Desmopressin-treatment promoted a significantly lower free water reabsorption in diazepam-treated group as referred to control rats. This results indicate that diazepam may promote impairments on renal tubular ions reabsorption and that it modifies the collecting tubule response to desmopressin. PMID- 8210692 TI - Anti inflammatory, analgesic, antiproteolytic and ulcerogenic activities of some new 1-[3-(aryloxy)-propyl]-diamines. AB - The anti-inflammatory activity of some new 1-[3-(aryloxy)-propyl] diamines using the carrageenin rat paw edema test has been investigated. Arthritis induced by Freund's adjuvant was also used. Writhing induced by acetic acid in rats was used to evaluate analgesic activity. The irritative and ulcerogenic action on the rat gastric mucosa was examined after oral administration. Antiproteolytic activity has also been studied. The experimental results are discussed from the point of view of structure activity relationships. PMID- 8210693 TI - Structural requirements for unsaturated fatty acids and fatty alcohols to induce optimal biological responses: an approach using model membranes. AB - The permeation induced by unsaturated fatty acids and fatty alcohols through the membrane of dihexadecyl phosphate vesicles was quantified, using [Ru(bpy)3(2+)] ions as a permeant probe. In both the free fatty acid and the free fatty alcohol series, the permeation induced by the unsaturated isomers is higher than that of the corresponding saturated analogues. Moreover the permeant effect associated with free fatty acids or free fatty alcohols is under the control of structural and conformational parameters: carbon chain length, number and position of the double bonds, and the geometry Z or E of the double bond. Optimal membrane perturbing effects are observed for compounds having a carbon chain length ranging from 18 to 20 carbon atoms, incorporating two or four Z double bonds in the center of the carbon chain. Good correlation has been found between the membrane perturbing effect quantified as PD50 values and some of the biological properties associated with these fatty lipids. The PD50 values obtained for free fatty alcohols are in fair agreement with anesthetic properties reported by different authors, (Pringle et al., 1981) while PD50 values obtained for free fatty acids show a good correlation with their activity on the superoxide respiratory burst induced by chemotactic peptides. These preliminary results led to the conclusion that as far as a biological activity directly associated with unsaturated fatty acids or alcohols, involved a membrane barrier passage, the measure of their permeant properties using a DHP vesicle model appears to be an excellent criterion for the quantification of optimal biological effects. PMID- 8210694 TI - Disposition of thiorphan in DOCA-salt and spontaneously hypertensive rats. AB - Thiorphan was administered intravenously (i.v.) at 10 mg/kg to conscious rats in two different models of hypertension to allow a comparison of pharmacokinetics. The two models were: 1) Deoxycorticosterone acetate (DOCA)-salt uninephrectomized rats; 2) Spontaneously hypertensive rats (SHR), and their respective normotensive controls; 3) Sprague-Dawley (SD) rats; and 4) Wistar-Kyoto rats (WKY). Pharmacokinetic parameters were calculated for total and unbound thiorphan in plasma. In normotensive SD and WKY rats, the volume of distribution, clearance and plasma protein binding of thiorphan were not significantly different. Furthermore, the apparent elimination half-life was not significantly different for total or unbound thiorphan amongst all models. The volume of distribution and plasma clearance for both unbound and total thiorphan, however, were lower in DOCA-salt rats when compared to normotensive control rats by 61-66% and 46-51%, respectively. In contrast, pharmacokinetic parameters for both unbound and total thiorphan were not significantly different between SHR and WKY rats. These results indicate that reduced clearance of thiorphan in DOCA-salt rats may be due to the co-administration of DOCA-salt or altered renal function of the hypertrophic remaining kidney and not solely due to hypertension. PMID- 8210695 TI - Effects of hydrochlorothiazide and captopril on the survival and heart weight of cardiomyopathic hamsters. AB - The current study investigated the effect of hydrochlorothiazide (HCTZ), and of captopril, on the survival and heart weight of cardiomyopathic hamsters (CMH). Groups of 51 CMH (about 200 days old) were orally treated with HCTZ (6 mg/kg), captopril (30 mg/kg), a combination of both drugs or vehicle alone (control group), for 217 days. Then survivors were sacrificed and the hearts weighed. The survival of the animals treated with HCTZ alone or in combination with captopril was similar, and was clearly increased when compared to controls (more than 70 days increase in median survival time). A more modest increase in survival occurred in animals treated with captopril alone. The efficacy of the diuretic therapy was consistent with fluid retention being the primary cause of death in CMH and demonstrated the usefulness of the model for the testing of new diuretics. HCTZ or captopril alone had no effect on the heart weight of survivors. However a reduction of cardiac hypertrophy (-18%) was seen when captopril and HCTZ were coadministered. This effect of the ACE inhibitor was considered to result from antagonism of the compensatory activation of the renin angiotensin system occurring in response to diuretic therapy. PMID- 8210696 TI - Phorbol ester (PMA) activates voltage-dependent Ca(2+)-channels in helical but not ring preparation of the rat aorta. AB - Effects of phorbol 12-myristate 13-acetate (PMA) on the helical and ring preparations from rat thoracic aorta was investigated in the present study. In helical strips, PMA produced biphasic contraction, i.e., sustained contraction followed by a phasic response superimposed on the sustained contraction. The phasic contraction was completely inhibited by removal of external Ca2+, whereas sustained contraction was not affected by the treatment. In the ring preparation, PMA produced only sustained contraction, whereas phasic contraction was not induced. On the other hand, in the ring preparation which had been treated with 15 mM K+, PMA was able to produce phasic contraction. Contractile response of the aorta to norepinephrine (NE) or clonidine in the ring preparations was significantly weaker than that in the helical strips. In the presence of nifedipine, however, these different sensitivity to NE between ring and helical preparations was not shown. These results suggest that an activation of C-kinase by PMA is able to stimulate voltage-dependent Ca(2+)-channels in the helical strips but not ring preparation of the aorta. An increased contractile response of the aorta to agonists in helical strips may be responsible for an increased activities of voltage-dependent Ca(2+)-channels. PMID- 8210697 TI - Perinatal development of amine, alcohol and phenol sulfoconjugations in the rat. AB - Development of the sulfoconjugating activities for amine, alcoholic and phenolic compounds was studied in hepatic 105,000 g supernatants of fetal and newborn rats. All activities in the fetus at the late stage of pregnancy were negligible or very low when compared with those of the adult female level. Amine and alcohol sulfoconjugating activities were low 2 days after birth, increased with age, and attained the adult female level 17 days after birth. In contrast, phenol sulfoconjugating activity was nearly half the level of adult female rats in the neonates 2 days after birth and was relatively constant before maturation. There were no sex-related differences in any of the activities in the immature rats, but in adult animals the activities for amine and alcohol were higher in the females than in the males; the opposite was observed for phenol sulfoconjugation. PMID- 8210698 TI - Dexamethasone treatment in utero enhances neonatal cholinergic nerve terminal development in rat brain. AB - Fetal glucocorticoid administration has been proposed to elicit both promotional and inhibitory effects on neuronal development. In the current study, pregnant rats were given 0.05, 0.2 or 0.8 mg/kg of dexamethasone on gestational days 17, 18 and 19, and the effects on development of central cholinergic projections was assessed on postnatal day 1 by measuring the specific binding of [3H]hemicholinium-3 to the high affinity choline transporter localized in cholinergic nerve terminal membranes. Dexamethasone produced a dose-dependent retardation of brain region growth, but enhanced [3H]hemicholinium-3 binding in both the forebrain and the midbrain + brainstem. At the highest dose, the promotional effect on [3H]hemicholinium-3 binding was lost in the forebrain, a region that is particularly sensitive during late gestation to inhibitory effects of glucocorticoids on neuronal development. These results indicate that, even in the face of growth retardation, glucocorticoids promote the development of central cholinergic projections; however, at high doses, inhibitory actions of the steroid can offset the promotional effects in some regions. PMID- 8210699 TI - Effects of carbon tetrachloride-induced chronic liver damage on glutathione and glutathione-dependent enzymes in rat gastric mucosa. AB - The present study investigated the relationship between the concentration of the reduced form of glutathione (GSH) and GSH-dependent enzyme activities in the gastric mucosa during chronic liver injury caused by carbon tetrachloride (CCl4) in rats. There were significant decreases in the mucosal GSH concentration and glutathione S-transferase (GST) activity as well as a significant increase in gamma glutamyltransferase (GGT) activity in rats exposed to CCl4 (all p < 0.001). However, no significant change was observed in glutathione peroxidase (GSH-Px) activity. A negative correlation was seen between the mucosal GSH concentration and GGT activity (p < 0.05) and a positive correlation between the GSH concentration and GST activity (p < 0.01). No correlation was noted between the GSH concentration and GSH-Px activity. Gastric mucosal damage, as evaluated by macroscopic observation and light microscopy, was more damaged in the rats exposed to CCl4 than in the control group. There was a significant correlation between histologic mucosal damage and GGT activity (p < 0.05) as well as a negative correlation between the number of macroscopic lesions and GSH and between the number of macroscopic lesions and GST (p < 0.01). From the observed abnormalities of GSH and GSH-dependent enzymes in the gastric mucosa of the rats exposed to CCl4, GSH content and the activities of GSH-dependent enzymes might play a role in the gastric mucosal defense mechanism during chronic liver injury. PMID- 8210700 TI - Protective actions of YM737, a new glutathione analog, against cerebral ischemia in rats. AB - Effects of YM737[N-(N-r-L-glutamyl-L-cysteinyl)glycine 1-isopropyl ester sulfate monohydrate], a new glutathione (GSH) analog more readily transported into cells than GSH, on cerebral ischemia were compared with those of GSH and some other drugs in rats subjected to occlusion of the bilateral carotid arteries. YM737 significantly reduced lethality, increased brain-water levels as measured by both dry-wet and NMR methods, and increased malondialdehyde (MDA) levels in the cerebral ischemic rats. On the other hand, pharmacological actions of GSH itself was less than those of YM737. In the ischemic rats used in the present study, there was no significant difference in 31P-NMR signals between the normal and the cerebral ischemic rats. These results suggest that YM737 showed anti-cerebral ischemic effects presumably due, in part, to inhibition of lipid peroxidative responses. PMID- 8210701 TI - ELISA determination and preliminary pharmacokinetics of modified human rIL-1 beta in dogs. AB - A single dose pharmacokinetic study with modified human Interleukin-1 Beta (IL-1 beta or DuP 118) was performed by injecting 5 micrograms/kg of drug into the jugular vein of three beagle dogs. Serial 5-ml plasma samples were removed from the dogs over a 120-minute period. DuP 118 plasma levels were measured using a sandwich ELISA technique capable of measuring concentrations ranging from 0.25 to 2 ng/ml with accuracy and precision constraints of less than +/- 20% variability. DuP 118 stored at -20 degrees C in dog plasma was stable for at least 1 month. Pharmacokinetic parameters were determined for the three dogs by standard model independent or non-compartmental methods. DuP 118 was rapidly distributed in the dog. The volume of distribution was approximately two-fold higher than the total body water of a lean dog. The terminal half-life was short, less than 30 minutes. Within approximately an hour after dosing, DuP 118 plasma levels were reduced 20 fold and were below the quantifiable limit of the assay. PMID- 8210702 TI - Reduced efficiency of copper transport from cytosolic to noncytosolic fractions in LEC mutant rat. AB - Long-Evans Cinnamon (LEC) mutant rat, which spontaneously develops a necrotizing hepatic injury at 4-5 months of age, exhibits an excess hepatic copper accumulation. Neonatal LEC rat showed higher ratio of cytosolic to noncytosolic copper contents than neonatal normal rat, suggesting that the efficiency of copper transportation into noncytosolic compartment is primarily inherently reduced in LEC rat. Additionally using northern blot analysis with neonates we suggested that the elevated metallothionein levels observed in adult LEC rat are probably secondary to elevated copper levels. PMID- 8210703 TI - Antitumor activity of acemetacin in mice bearing colon 26 carcinoma: a preliminary report. AB - The antitumor activity of acemetacin (ACM) was examined in mice bearing colon 26 carcinoma and its effect was compared with indomethacin (IND). The addition of ACM (0.001-0.003%) to drinking water prolonged the survival time of mice bearing colon 26. On the other hand, prostaglandin E2 (PGE2) reduced the effect of ACM. The results suggest that the antitumor activity of ACM may be associated with the reduction of PGE2 levels. PMID- 8210704 TI - l-5-formyltetrahydrofolate and l-5-methyltetrahydrofolate rescue in L1210 leukemia treated with high methotrexate doses. AB - Highly purified 5-l-methyltetrahydrofolate (m-THF) and 5-l-formyl-THF (f-THF) preparations were compared for rescuing from methotrexate (MTX) toxicity in DBA2 mice transplanted with L1210 leukemia. Mice received two doses of reduced folates (2 mg/kg, s.c.) 16 and 24 h after a single s.c. MTX dose. f-THF was 1.8 time more effective than m-THF in protecting tumor cells from MTX (800 mg/kg). This MTX dose caused a 57% fall in circulating polymorphonucleates, which was prevented by both reduced folates. Treatment with 800 mg/kg of MTX plus m-THF was 1.5 fold more effective than the same MTX dose plus f-THF in increasing survival time of tumor-bearing mice. These data suggest a higher selectivity and efficacy of l-m THF with respect to l-f-THF in rescuing from MTX toxicity. PMID- 8210705 TI - Successful mass vaccination against hepatitis B virus in a hyperendemic area in Italy. AB - A pilot model of vaccination against hepatitis B virus suitable for mass vaccination was performed from 1983-1989 in the hyperendemic area of Afragola, a town of 60,000 inhabitants near Naples. In this area of high prevalence of HBsAg carriers, a consistent reduction in the incidence of hepatitis B virus infections as well as chronic related liver complications was observed. PMID- 8210706 TI - The role of T helper lymphocyte subsets in antiviral immunity. PMID- 8210707 TI - Immunobiology and pathogenesis of hepatitis C virus infection. PMID- 8210708 TI - Replication and multiplication of hepatitis C virus genome in human foetal liver cells. AB - The ability to obtain primary long-term cultures of human foetal hepatocytes maintaining liver differentiation characteristics in serum-free medium prompted us to test their susceptibility to hepatitis C virus infection. Using PCR, we detected the presence of the HCV RNA-positive strand in the supernatants and in the cells of the virus-infected hepatocyte cultures, at various times post infection. Evidence of effective virus genome replication and multiplication was also based on the time-dependent appearance of the putative HCV RNA-negative strand, the detection of virus replicative intermediates and an increase in HCV genomic templates in the HCV-infected cells. PMID- 8210709 TI - The human bone-marrow-derived B-cell line CE, susceptible to hepatitis C virus infection. AB - The euploid-diploid cell line CE, issuing spontaneously from a normal human bone marrow culture, displays B-cell differentiation and activation markers and is positive (> or = 90% of cells) for Epstein-Barr nuclear antigens. CE suspensions were inoculated with serum from a patient chronically infected with hepatitis C virus (HCV). After inoculation, the cells were regularly subcultured with a split ratio of 1:2 every 4-6 days. RNA extracted as late as 65 days after infection from the inoculated cells were positive by polymerase chain reaction for the 5' untranslated region of the HCV genome, and viral antigens were detected by immunofluorescence. Virus was also released from the infected cells into the medium. Intracellular HCV could be successfully passaged twice in CE cultures. On the basis of these findings, the CE cell line appears promising as a model for studying HCV replication and persistent infection in vitro. PMID- 8210710 TI - Early steps in fusion between Epstein-Barr virus and a human hepatoma cell line (Li7A). AB - Epstein-Barr virus, the causative agent of mononucleosis and several human cancers, infects cells via complement receptor type 2 (CR2). Expression of this receptor is restricted to B lymphocytes, some epithelial cells and immature thymocytes; expression of CR2-like proteins has been also found on T cells. In the present report, we identified the presence, on the membrane of Li7A cells, of a novel EBV receptor distinct from CR2 capable of triggering fusion with EBV virions with more rapid kinetics than that found with lymphoblastoid cells (Raji). PMID- 8210711 TI - Do mutant woodchuck hepatitis viruses play a role in hepatocellular carcinogenesis? AB - Although hepadnaviruses are implicated in the aetiology of hepatocellular carcinoma, the pathogenic mechanisms involved remain uncertain. Clonally propagated integrations of hepadnaviral DNA into cellular DNA can be demonstrated in most virally induced hepatocellular carcinomas. Integration occurs at random sites in cellular DNA, but the highly preferred sites in viral DNA are adjacent to the directly repeated sequence, DR1, less often DR2, or in the cohesive overlap region. Integrants invariably contain simple deletions or complex rearrangements that have been thought to occur after integration. We report here the detection, in the serum of woodchucks with hepatocellular carcinoma, of mutant woodchuck hepatitis viruses that are strikingly similar to the rearranged genomes found previously as integrated sequences in cellular DNA. Of the four mutants studied, two had large inverted duplications, one a 219 nucleotide direct duplication, and one a 219 nucleotide deletion. Virus-virus DNA junctions occurred either adjacent to DR1 or DR2 or in the cohesive overlap region at topoisomerase I cleavage sites. Thus, it is possible that rearrangement of the hepadnavirus genome precedes integration of viral DNA into cellular DNA and that mutant genomes that are preferentially integrated into cellular DNA have an aetiological role in hepatocarcinogenesis. PMID- 8210712 TI - Hepatitis B virus preC mutants in human hepatocellular carcinoma tissues. AB - A comparative analysis of preC sequences of hepatitis B virus (HBV) in human hepatoma (hepatocellular carcinoma; HCC) tissues and non-tumoral liver samples from HCC patients was performed. Ten out of 17 HCC tissue samples exhibited an amino acid substitution at the level of the distal cysteine residue of the HBV preC region, while generation of a TAG translational stop codon was observed in 4 of these samples. Interestingly, substitution of the distal cysteine residue was not observed in non-tumoral liver (available from 8 of the 17 patients), thus suggesting either that a selection among different HBV variants occurs in HCC cells, or that modifications to the conformation and stability of the HBV capsid protein may play a role in the process of selection and escape of transformed liver cells. PMID- 8210713 TI - Direct detection of HBV preC mutants in heterogeneous viral populations by a modified DNA sequencing method. AB - A modified method for the direct sequencing of double-stranded DNA products of PCR amplification is described and has been applied to the analysis of hepatitis B virus (HBV) preC/C region in samples from persistently infected patients with chronic hepatitis. Data was obtained from both hepatitis B e antigen (HBeAg) positive and -negative chronic carriers. A high prevalence of mixed viral populations (wild-type genomes and mutated sequences with a TAG stop codon in the distal preC region at position 1895-1897) was shown in the HBeAg-positive group; a homogeneous (either mutated or wild-type) viral population was detected in all but one of the long-term HBeAg-negative, untreated chronic carriers, thus suggesting that pre-core mutants can be rapidly generated and selected during the natural course of HBV infection. PMID- 8210714 TI - Detection of the hepatitis B virus major pre-core mutation by the amplification refractory mutation system technique. AB - HBeAg/anti-HBe seroconversion is associated, in some patients affected by type B chronic active hepatitis (CAH), with the occurrence of HBV pre-core mutants characterized by a common G-A change at codon 83. Since this mutation has important clinical correlations, we tried to develop a fast and reliable PCR test based on the amplification refractory mutation system (ARMS) technique, which has been successfully used to identify point mutations associated with genetic diseases. Following this approached, we analysed HBV particles isolated from 7 patients with anti-HBe CAH and previously characterized by DNA sequencing. Sera containing only wild type or mutant HBV DNA or a combination of both showed a discrete amplification product only in the presence of the specific wild type or mutant upstream primer. These results confirm the efficacy of the ARMS technique in detecting in a rapid and specific fashion the most common and clinically relevant HBV pre-core mutation. PMID- 8210715 TI - The hepatitis B virus transactivator HBx causes elevation of diacylglycerol and activation of protein kinase C. AB - Chronic infection with hepatitis B virus (HBV) is accompanied by an increasing risk of developing hepatocellular carcinoma. There are indications that the HBx protein of HBV is involved in the process of tumour formation. HBx also transactivates several transcription factor binding sites. Recently, we reported that HBx can use a tumour promotor pathway for transactivation. In particular, we found that transactivation of the binding motif for transcription factor AP-1 (JUN/FOS) by HBx is dependent on functional protein kinase C (PKC), as indicated by abolition of the transcriptional stimulation following downregulation or inhibition of the enzyme. Moreover, HBx activates PKC, probably via increasing the endogenous PKC activator sn-1,2-diacylglycerol (DAG). Here we extend these data and report on the time course of PKC activation. We found that activation of PKC by HBx is transient and differs from activation of PKC by the ras oncogene product or phorbol ester in that it does not lead to rapid downregulation of the enzyme subsequent to the activation. Moreover, we provide evidence that an increase in cellular DAG is observable not only as an early event in response to HBx but also in cell lines transformed after transfection with HBV DNA and stably expressing HBx. Besides its important role in the regulation of cellular genes, PKC is also the intracellular receptor for tumour-promoting agents and an activator of proto-oncogenes, suggesting that our observations might provide an explanation for the oncogenic properties of HBx. PMID- 8210716 TI - Interleukin-6 production by human hepatoma lines is related to a low degree of cell differentiation. AB - In this study, we showed by Northern blot analysis and bioassays that scarcely differentiated human hepatoma cell line HA22T/VGH constitutively produces interleukin-6 (IL6). This cytokine was produced neither by moderately differentiated Li7A nor by well-differentiated HepG2 human hepatoma cell lines. The finding that transcripts for IL6 were not present in 2.2.15 cells, a HepG2 derived clone transfected with the intracellular replicative form of hepatitis B virus (HBV) DNA, suggests that production of this cytokine is not affected by HBV encoded gene products, but is more likely related to the dedifferentiated state of hepatoma cells. PMID- 8210718 TI - Transcutaneous O2 and CO2 monitoring of bronchial responsiveness in FEV1 non responder asthmatics during ketotifen and placebo treatment. AB - Effects of ultrasonically nebulized distilled water (UNDW) on PtcO2 and PtcCO2 time courses were studied in 26 mild asthmatics (FEV1 non-responders) in basal conditions and monitored after 2, 6, 12 and 18 weeks of randomly allocated treatment with ketotifen 1 mg b.i.d. or placebo. Magnitude and duration of both PtcO2 and PtcCO2 changes due to UNDW inhalation were progressively normalized only by ketotifen. Partial but significant protection against UNDW-induced hyperventilation was achieved after 2 weeks of treatment, complete protection (also against UNDW-induced hypoxia) being achieved later. In view of the CO2 dependency of respiratory drive and the primary structural targets of the hypo osmotic bronchial challenge employed, these results suggest that ketotifen may affect the mucosal structures of the bronchial airways, thereby acting as a mucosal protective drug. PMID- 8210719 TI - Frequency dependence of oscillatory resistance in healthy primary school children. AB - With the use of the forced oscillation technique, respiratory input impedance was measured in 371 healthy children, aged 5-12 years. How impedance values varied with height (age) and gender and to what extent negative frequency dependence of oscillatory resistance existed in these children was investigated. Negative frequency dependence of resistance between 8 and 28 Hz was a common finding in all height categories. With increasing height, resistance decreased and reactance increased in all children. Below 140 cm of height, resistance values at 8 Hz were higher, and reactance values at 8 Hz were more negative in girls than in boys. At heights above 140 cm the reverse was found. Resonant frequency was found to be higher in boys than in girls. The incidence of negative frequency dependence of resistance (FD) decreases during growth. Over heights of 130-160 cm, more negative FD existed in boys than in girls. It can be concluded that negative FD between 8 and 28 Hz can be found in healthy children up to 12 years of age, most pronounced in boys, not necessarily implicating pulmonary pathology. PMID- 8210717 TI - Oxidants from neutrophil myeloperoxidase do not enhance elastase-induced emphysema in the hamster. AB - Alpha-1-protease inhibitor is susceptible to oxidative impairment by the neutrophil myeloperoxidase (MPO) system. The purpose of this study was to assess the effect of the MPO oxidant system on elastase-induced emphysema in the hamster. Intratracheal instillation of 200 micrograms of human neutrophil elastase (HNE) induced a significant secretory cell metaplasia (SCM) and airspace enlargement [23% increase in mean linear intercept (MLI) as compared with control values]. Instillation of MPO system components [0.6 international units (U) of MPO, 5.5 U of glucose oxidase and glucose (0.02 M)] along with 200 micrograms HNE failed to enhance the severity of the SCM or emphysema induced by HNE alone. A second experiment was carried out using 50 micrograms of porcine pancreatic elastase (PPE) to induce emphysema. PPE produced a significant 45% increase in MLI, but the MPO system combined with PPE failed to enhance the emphysema induced by PPE alone. The MPO system alone had no measurable effect on airspace size or SCM. In vitro studies showed that PPE was partially inactivated by the MPO system; a 56% loss of elastolytic activity occurred during a 6-min incubation of PPE with the MPO system. This may explain why the MPO system did not exacerbate PPE-induced injury, but it does not explain the lack of enhancement for HNE. A 6 minute incubation of HNE with the MPO system resulted in a nonsignificant 10% decrease of elastolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210720 TI - CO diffusing capacity in a general population sample: relationships with cigarette smoking and airflow obstruction. AB - The single-breath carbon monoxide diffusing capacity (DLCOsb) was measured together with ventilatory lung function tests as part of a survey of a general population sample living in Northern Italy (n = 2,481). Based on answers to an interviewer-administered questionnaire, subjects free of respiratory symptoms or diseases were identified. Data from subjects who had never regularly smoked cigarettes were used to derive reference equations for the test indexes, and data from the remaining subjects who had smoked were used to derive regression equations incorporating a term expressing cigarette consumption (cube root of pack-years) and a term indicating current smoking decrement, in order to obtain expected DLCOsb percent predicted. Neither number of cigarettes smoked daily or duration of smoking, in smokers, nor duration of smoking or years since quitting smoking, in ex-smokers, entered significantly the multiple-regression model. The mean values of DLCOsb were only slightly affected by the increasing degree of airway obstruction. When subjects with confirmed asthma were analyzed, after stratifying for different levels of FEV1/FVC ratio, increased mean value of DLCOsb (over 100%) was found in those with an FEV1/FVC ratio between 75 and 65%. This cross-sectional analysis suggests that there is a decrease in DLCOsb with cumulative cigarette consumption even in healthy subjects. Further, it confirms the clinical observations of high DLCOsb values in asthmatic patients, at least in those with an initial degree of chronic airflow obstruction. PMID- 8210721 TI - Breathing pattern during and after maximal exercise testing in young untrained subjects and in obese patients. AB - More rapid and more shallow breathing (RSB) than usual, manifested by a lower tidal volume and greater breathing frequency at a given level of ventilation, may be caused by inspiratory muscle fatigue and pulmonary congestion. It has been observed during recovery in young trained adults after very high exercise levels and in middle-aged patients with cardiac disease, after their maximal work load. We studied the breathing pattern during and after exercise testing up to the maximal work capacity in a group of normal untrained, young people and in a group of young obese subjects. RSB was present in normal subjects after a work load which required a maximal O2 consumption near the theoretical value (93% in our cases) and was not present in obese patients probably because neither inspiratory muscle fatigue, nor pulmonary congestion occurs in these subjects. Maximal heart rate at peak of exercise was significantly higher in normal subjects and a direct correlation between delta Vt and maximal heart rate was found in all normal subjects. This is compatible with the hypothesis that RSB is mainly due to an initial interstitial pulmonary edema, as supposed by other authors. PMID- 8210722 TI - Decreases in serum cholesterol levels in advanced lung cancer. AB - Serum lipid concentrations, including triglycerides, free fatty acids, phospholipids, low-density lipoproteins, total cholesterol, high-density lipoprotein (HDL) cholesterol and lipoprotein fractions, were investigated in 43 male patients with advanced nonresectable lung cancer and 37 age- and sex-matched healthy male controls. The cancer patients as a group demonstrated significantly lower total cholesterol and HDL cholesterol as compared with the healthy controls. There were no significant differences between the various fractions of lipoproteins in the two patient groups. These results suggest hypocholesterolemia including decreased serum HDL cholesterol in advanced lung cancer patients. PMID- 8210723 TI - Conservative treatment of empyema in children. AB - Seventy-two children with no underlying diseases were treated for empyema. Radical surgical approaches like decortication were necessary for only 3 children. In 66 children tube drainage was applied. Staphylococcus aureus was cultured or was shown in Gram's stain in 32 (44%) and children with this microorganism had longer duration of tube drainage (p < 0.05). The period for normalization of chest X-ray was positively related with the age of the patient (p < 0.05). In 60 of 72 children, chest X-ray was normal after 3 months. Follow up of the patients 18 months after the infection revealed that pulmonary radiograms were normal in all cases and pulmonary function tests were within normal limits in all of the tested children (n = 25). It is emphasized that avoiding major surgical approaches must be encouraged in childhood empyema. PMID- 8210724 TI - Pneumocystis carinii infections in HIV-infected hemophiliacs during aerosolized pentamidine prophylaxis. AB - The frequency, presentation, diagnosis and clinical course of Pneumocystis carinii infections (PCI) were studied during aerosolized pentamidine prophylaxis (AP) and its impact on the spectrum of AIDS-related and other pulmonary infections in HIV-infected hemophiliacs. We conducted an open study on primary (PP) and secondary (SP) AP. Breakthrough P. carinii infections (BPCI) and other infectious complications were analyzed retrospectively. Hemophiliacs without prior P. carinii pneumonia (PCP) who had been reluctant to any prophylaxis and who developed PCP served as control group. Statistical analysis of the efficacy of prophylaxis was performed by calculating confidence intervals of binomial p. Of 73 hemophiliacs (56 on PP and 17 on SP) 10 developed BPCI (7 in PP and 3 in SP) during a mean observation time of 14.9 months (range 0.5-30); total 13.6% (6.7%; 23.7%), PP 12.5% (5.1%; 24%), SP 17.6% (3.7%; 43.4%), confidence intervals at a level of 95%. Three BPCI presented atypically with cavitation (1), pneumothorax (2), Pneumocystis pleuritis (1), dissemination (2) as compared to none in the control group. Sensitivity of bronchoalveolar lavage (BAL) was 88.9%, specificity 100% (both 100% in the control group). PCP was the leading AIDS manifestation (21.3%), CNS manifestations taken together were more frequent (36.2%). Bacterial pneumonia was the most frequent respiratory infection. One patient of the study group with recurrent pneumothorax possibly died of BPCI as compared to no BPCI-related deaths in the control group. Efficacy of prophylaxis in hemophiliacs was comparable to other risk groups. AP alone may be insufficient for the control of PCI in patients with long-term profound immunodeficiency, especially in SP. 30% of BPCI presented atypically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210726 TI - A comparison of bag mask and mouth mask ventilation in anaesthetised patients. AB - Anaesthetic residents used bag valve mask (BVM) or mouth mask (MM) ventilation, both with an O2 flow of 15 l min-1 to ventilate 30 ASA I or II anaesthetised patients for 4 min prior to endotracheal intubation. Mean nasopharyngeal O2 was higher with BVM (BVM 95% (S.D. 3%) MM 54% (S.D. 12%)). End tidal CO2 (ETCO2) was similar in both groups (ETCO2% at 4 min: BVM 4.65 (S.D. 0.84) MM 4.53 (S.D. 0.54)) but respiratory rate was faster with BVM (BVM 17 min-1 (S.D. 5) MM 12 min 1 (S.D. 4)). Peak (Paw) and mean (Paw) airway pressures were higher with MM and MM produced significant expiratory pressure [cmH2O: BVM Paw 16.7 (S.D. 5.3) Paw 4.2 (S.D. 2.1) MM: Paw 20.9 (S.D. 5.2) Paw 7.8 (S.D. 2.1)) minimum expiratory pressure: MM 2.4 (S.D. 1.1) BVM 0.2 (S.D. 0.4). Gastric insufflation was detected in two MM and two BVM patients. This tended to be more severe with MM ventilation. Although MM ventilation has some important disadvantages it can be used effectively by resuscitators with little or no experience in its use. PMID- 8210725 TI - Inflammatory endotracheal polyp resolved after antibiotic treatment. AB - We describe a rare case of asymptomatic inflammatory endotracheal polyp resolved by antibiotic treatment. Histological examination of biopsy specimens showed an inflammatory polyp consisting of fibrovascular stroma and sparse lymphocyte infiltration. The size of the polyp was unchanged during 3 months without any treatment and its etiology was unclear. Although a bacterial organism was never proven, the polyp decreased remarkably under treatment with an oral antibiotic (ciprofloxacin) and did not recur for 6 months. Antibiotic treatment may be of value for inflammatory tracheobronchial polyps in cases of unclear etiology. PMID- 8210727 TI - Influence of age on the survival rate of out-of-hospital and in-hospital resuscitation. AB - During a 9-year period 1472 cardiopulmonary resuscitations were analysed. Five hundred seventy-two were in-hospital and 898 out-of-hospital resuscitations. Of the out-of-hospital resuscitations 495 (55.1%) patients were less than 70 years and 403 (44.9%) older than 70 years. Survival in the former group was 71 (14.3%) in the elderly group 44 (10.9%) (P < 0.1). In the in-hospital population 245 (43%) were below 70 years and 327 patients above 70 years (57%). Seventy patients (28.2%) in the former group and 46 (14.1%) in the latter group survived (P < 0.01). The statistical analysis of the out-of-hospital resuscitations indicates no significant difference in the survival rate of patients younger than 70 years compared to those above 70 years. The survival rate however for patients above 70 years in the in-hospital group was significantly worse, probably attributed to multimorbidity of the older in-hospital patients. The results in our study indicate that old age is not a determinant of prognosis or outcome after CPR. PMID- 8210728 TI - The effect of intravenous magnesium administration on aortic, right atrial and coronary perfusion pressures during CPR in swine. AB - OBJECTIVE: To determine the effect of magnesium administration on aortic, right atrial and coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR). DESIGN: Twelve swine weighing 23.2 +/- 3.1 kg were instrumented for CPP, aortic systolic (AOSP) and aortic diastolic (AODP) pressures. INTERVENTION: Ventricular fibrillation was induced and after 20 min of CPR the animals were allocated to receive epinephrine 0.2 mg/kg, or epinephrine 0.2 mg/kg plus magnesium 0.14 g/kg. Epinephrine was repeated every 5 min. Arterial blood gases were determined during normal sinus rhythm and prior to drug administration. RESULTS: Pressures were recorded and averaged over four consecutive 5-min intervals following initial drug administration. AOSP, AODP and CPP were compared using an analysis of covariance. AOSP was statistically lower in the group receiving magnesium. There was a trend toward lower AODP and CPP in the group receiving magnesium as well. These statistical differences and trends were absent after adjusting for pressures during normal sinus rhythm and serum bicarbonate prior to drug administration. CONCLUSIONS: In this model of prolonged cardiac arrest, the administration of magnesium with epinephrine appeared to have a negative effect on aortic pressures during CPR. Further study is needed to determine the confounding effect of serum bicarbonate on the response to epinephrine and magnesium during CPR. PMID- 8210729 TI - Survival from cardiac arrest in an accident and emergency department: the impact of out of hospital advisory defibrillation. AB - A prospective 1-year audit of cardiac arrests treated in the Accident and Emergency department of the Royal Infirmary, Edinburgh is presented. During the period January 1st, 1991 to December 31st, 1991, 325 patients with cardiac arrest were treated. Two-hundred ninety-seven of these were 'out-of-hospital' and 28 were 'in-department' arrests. Of patients with 'out-of-hospital' ventricular fibrillation/pulseless ventricular tachycardia 22.8% were discharged. Survival rates for patients with asystole or electromechanical dissociation were very poor. The impact of semiautomatic out-of-hospital defibrillation upon the survival and number of patients presenting to the department is discussed. PMID- 8210730 TI - Establishment and results of an EMT-D program in a two-tiered physician-escorted rescue system. The experience in Berlin, Germany. AB - Early defibrillation by emergency medical technicians or even less qualified personnel has been shown to improve survival rates for out-of-hospital cardiac arrest caused by ventricular fibrillation. It has been questioned whether these favourable results can be applied within the context of physician-attended emergency medical systems. Taking into consideration the results of a pilot study and after a careful analysis of the logistic and epidemiological background, the first German EMT-D program was introduced in the former West Berlin in December 1988. The first 2 years of experience with 499 technician-initiated resuscitation attempts in which the mobile intensive care unit of Klinikum Steglitz was involved, confirmed the results of the pilot study with an improved long-term survival rate (18%) for patients with ventricular fibrillation. We conclude that EMT defibrillation should be introduced in emergency physician-attended two tiered emergency medical systems, whenever a thorough analysis of the existing rescue systems exhibits a 'relevant frequency' of resuscitation and response interval of 15 min or less. PMID- 8210731 TI - Quality and efficiency of bystander CPR. Belgian Cerebral Resuscitation Study Group. AB - Incorrectly performed bystander CPR might compromise survival of the cardiac arrest patient. We therefore evaluated the outcome in 3306 out-of-hospital primary cardiac arrests of which 885 received bystander CPR. bystanders performed CPR correctly in 52%, incorrectly in 11%, 31% performed only external chest compressions (ECC) and 6% only mouth-to-mouth ventilation (MMV). The initial ECG in cases without bystander CPR was ventricular fibrillation in 28% (95% confidence interval: 27-30%); 45% (41-50%) and 39% (29-48%), respectively when bystander CPR was performed correctly or incorrectly; 43% (37-49%) when only ECC was applied and 22% (11-33%) when only MMV was practiced. Long term survival, defined as being awake 14 days after CPR, was 16% (13-19%) in patients with correct bystander CPR; 10% (7-14%) and 2% (0-9%), respectively when only ECC or only MMV was performed; 7% (6-8%) when no bystander was involved; 4% (0-8%) when bystander CPR was performed incorrectly. Bystander CPR might have a beneficial effect on survival by maintaining the heart in ventricular fibrillation by ECC. A negative effect of badly performed bystander CPR was not observed compared to cases which had not received bystander CPR. PMID- 8210732 TI - Rhythm changes during resuscitation from ventricular fibrillation. AB - Defibrillation of patients with primary ventricular fibrillation (VF) results in a variety of rhythm changes. We analysed these changes in rhythm in 200 patients, using the American Heart Association's recommendation of two defibrillations prior to drug therapy. Sixty-three (31.5%) patients were immediate survivors with 38 (19%) being discharged from hospital alive. There was no difference between the age of immediate survivors (66.5 years, S.D. = 11.2) and non-survivors (68.3 years, S.D. = 13.7, P = 0.37). Immediate survivors were significantly more likely to be discharged alive from hospital if they were younger (70.0 years, S.D. 8.5 vs. 62.1 years, S.D. 15.8, P = 0.014). Increasing delays to the initiation of basic life support (CPR) and to defibrillation were associated with significantly less likelihood of cardioversion to sinus rhythm (P < 0.005 and P < 0.002, respectively). Those patients who stayed in VF were not more likely to be defibrillated into asystole or electro-mechanical dissociation. Seventeen percent (34) of patients were defibrillated to sinus rhythm after the first defibrillation and 14% (19) after the second, with similar hospital discharge rates (62% and 58%, respectively). Sixty percent (32) of patients in sinus rhythm, after two defibrillations, were discharged alive, compared to only 4% (6) of those patients not in sinus rhythm after two defibrillations. Our data provide new information on rhythm changes during resuscitation and supports the need for the earliest possible initiation of basic life support and defibrillation to improve survival from cardiac arrest due to ventricular fibrillation. PMID- 8210733 TI - Initial countershock in the treatment of asystole. AB - BACKGROUND: Routine provision of defibrillatory countershock (CS) in the initial management of asystolic cardiac arrest has been advocated because certain cases of ventricular fibrillation (VF) may present as asystole (AS). OBJECTIVE: To determine the value of initial CS versus endotracheal intubation and pharmacologic therapy alone in the treatment of asystolic cardiac arrest. DESIGN/PARTICIPANTS: A retrospective analysis of data collected prospectively during a multicenter study of out-of-hospital cardiac arrest. The study subjects were all patients whose initial cardiac arrest rhythm was AS and were treated with standard advanced cardiac life support (ACLS). SETTING: Six urban emergency medical services (EMS) systems. INTERVENTION: Patients in AS were treated initially with CS followed by ACLS therapy (CS Group), and were compared to those patients receiving endotracheal intubation and pharmacologic therapy alone (No CS Group). OUTCOME MEASURES: Those receiving initial CS were compared to those not receiving CS using both Chi-square and logistic regression analysis. Outcome parameters included: rates of return of spontaneous circulation (ROSC), emergency department admission, hospital admission and hospital discharge. RESULTS: Of the 194 patients presenting with AS, 77 received CS as their initial therapy. Of these, 13 (16.9%) had ROSC compared to 27 of the 117 (23.1%) from the No CS Group (P = 0.30). Emergency department and hospital admission rates were not significantly different; 13.0% versus 18.0% (P = 0.36), and 13.0% versus 11.1% (P = 0.69) for CS versus No CS, respectively. None of the patients in the CS Group were discharged alive versus two (1.7%) from No CS (P = 0.52). Of 42 patients with bystander-witnessed cardiac arrests, 13.3% in the CS Group had ROSC compared to 40.7% in the No CS Group (P = 0.07). Emergency department admission rates were 6.7% for the CS Group and 33.3% for the No CS Group (P = 0.07); while hospital admission rates were 6.7% and 22.2%, respectively (P = 0.39). When these comparisons were adjusted for bystander-initiated CPR, CPR interval, and paramedic response interval, the P-values became 0.10, 0.05 and 0.17, respectively. CONCLUSIONS: Although, statistically, the results for both groups were not distinguishable, outcomes for asystolic patients had a tendency to be better when the initial therapy did not involve CS. Larger study populations are recommended to confirm these preliminary observations. PMID- 8210734 TI - The optimum timing of resuscitative thoracotomy for non-traumatic out-of-hospital cardiac arrest. AB - Open-chest cardiopulmonary resuscitation (CPR) is a promising method for non traumatic cardiac arrest. In this preliminary study, we investigated the optimum timing of thoracotomy which brings high rate of return of spontaneous circulation (ROSC) and keeps the incidence of unnecessary thoracotomy minimal. Ninety-five adult patients with non-traumatic out-of-hospital cardiac arrest were analyzed. Of those, 26 patients were treated by the open-chest CPR in a prospective consecutive fashion. In this group, the ROSC rate was investigated in connection with the interval from hospital arrival, or ambulance call, to thoracotomy. Another 69 patients were treated by standard CPR. In this uncontrolled group, the interval from arrival at hospital to ROSC was investigated to define the 'natural hospital course' by the conventional treatment. Patient characteristics in the open-chest CPR group and the standard CPR group were similar. In the open-chest CPR group, 15 patients obtained ROSC. There was a tendency that the ROSC rate was highest in the patients with thoracotomy within 5 min of hospital arrival and declined as the timing of thoracotomy was delayed. Similar tendency was noted when the timing of thoracotomy was counted from the ambulance call. In the standard CPR group, only two patients obtained ROSC during the initial 5 min of hospital course. These results suggest that thoracotomy within 5 min of hospital arrival brings the highest ROSC rate while keeps the incidence of unnecessary thoracotomy acceptable. PMID- 8210735 TI - Performance of an established system of first responder out-of-hospital defibrillation. The results of the second year of the Heartstart Scotland Project in the 'Utstein Style'. AB - The Heartstart Scotland project for out-of-hospital defibrillation covers the whole of Scotland, a population of approximately 5,102,400 (14.9% > 65 years, 48.3% male). All 395 ambulances in Scotland have been equipped with an automated external defibrillator and crews are trained in basic cardiopulmonary resuscitation and defibrillator use (EMT-D). Between 1 May 1990 and 30 April 1991 a total of 1700 cardiac arrests was reported by the ambulance service. Of the 1676 arrests which we could trace, 63% were witnessed. A total of 1383 (83%) of all patients were declared dead on arrival at hospital or in the emergency department, 119 (7%) died in hospital and 174 (10%) were discharged alive. Of the 174 survivors, 87% were conscious and normal at discharge, 9% had moderate residual disability and 2% severe disability. Survival of patients discharged alive from hospital was 85% at 1 year. Defibrillation was undertaken in 71% of the reported cardiac arrests. Survival of bystander witnessed arrests was increased from 7 to 15% with bystander CPR (P < 0.005). If the cardiac arrest was witnessed by the ambulance crew and required defibrillation, survival to discharge was 39%. Of bystander witnessed arrests reached while still in VF (n = 643), 11% were discharged alive. Patients who were defibrillated within 4 min of arrest had a 43% survival rate to hospital discharge. PMID- 8210736 TI - The new recovery position, a cautionary tale. AB - In November 1992 the European Resuscitation Council issued new guidelines which included the description of a modified recovery position. Anecdotal reports have suggested that this 'new' position may result in obstructed venous return in the dependent arm. The findings of a small study to evaluate the 'new' recovery position are reported here. In a group of six healthy adult volunteers measurements of digital temperature, plethysmographic wave form and transcutaneous oxygen saturation were made in the previously favoured semi-prone recovery and repeated in the 'new' position. In the 'new' position 67% of the study group developed signs of venous or venous and arterial obstruction; no such complication was encountered when the same individuals were placed in the semi prone recovery position. The need to position unconscious persons in some form of recovery position is emphasised, however, the suggestion that the semi-prone position be re-adopted is offered for discussion. Alternatively, adequate monitoring of perfusion and venous drainage in the dependent limb must be undertaken if the 'new' recovery position is chosen. PMID- 8210737 TI - Recovery position. PMID- 8210738 TI - [Therapy for lung cancer in view of internal medicine]. PMID- 8210739 TI - [Therapy for lung cancer in view of surgery]. PMID- 8210740 TI - [Medical treatment of acute and chronic pulmonary thromboembolism]. PMID- 8210741 TI - [The surgical treatment for pulmonary thromboembolism]. PMID- 8210742 TI - [Treatment of sleep apnea syndrome]. PMID- 8210743 TI - [Operative surgery of obstructive sleep apnea syndrome]. PMID- 8210744 TI - [Spontaneous pneumothorax, giant bulla: from the view of internal medicine]. PMID- 8210745 TI - [Spontaneous pneumothorax and giant emphysematous bullae: from surgical site]. PMID- 8210746 TI - [Nonsurgical treatment of bronchiectasis and pulmonary abscess]. PMID- 8210747 TI - [Indication for surgical treatment of bronchiectasis and pulmonary abscess]. PMID- 8210748 TI - [Assessment of myocardial viability by exercise stress-redistribution myocardial scintigraphy with thallium-201: the usefulness of C-map]. AB - Standard exercise (Ex)-redistribution (RD) myocardial imaging with thallium-201 (201Tl) may not differentiate viable myocardium from necrosis. This study was intended to clarify whether 201Tl washout rate (WOR) abnormality after Ex can detect myocardial viability in the myocardium with perfusion defect using routine RD image. We performed Ex-RD (three hours after) myocardial tomography with 201Tl in 29 patients with coronary artery disease. From myocardial tomography, 201Tl distribution Bull's-eye maps (Ex and RD) and WOR Bull's-eye map were made. At RD image before PTCA, by referring to the original image, the activity of the myocardial region below 40% to 55% of the maximal 201Tl activity was considered as perfusion defect (RD-Map). Then we constructed a new image (C-Map) by adding the location of WOR abnormality (< or = 30%) to the RD-Map and each map was divided into 17 segments. If the defect-segment in the RD-Map corresponded to WOR abnormality, the segment in the C-Map was judged as viable (no defect). The C-Map and myocardial imaging after PTCA (Post-Map) were compared. In the RD-Map before PTCA, defect was found in 152 segments but in the C-Map they decreased to 59 segments, while defect was found in 62 segments in the Post-Map. In 23 patients the number of defect-segments in the C-Map decreased as compared with those in the RD-Map. And in 22 of them, the Post-Map showed the reduction of defect segments in comparison with the RD-Map, but in one of them defect did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210749 TI - [International normalized ratio (INR) for optimal anticoagulant therapy]. AB - Optimal therapeutic ranges for an oral anticoagulant therapy has been discussed for many years. Prothrombin time, prothrombin time ratios (PTR) and thrombotest have been employed so far, but, recently, International Normalized Ratio of prothrombin time (PT-INR or INR) has been introduced. We investigated paying special interest to INR, the effectiveness of oral anticoagulant therapy in 170 prosthetic valve patients and in 157 patients with various cardiovascular diseases who received warfarin at two different centers. The thrombotest, prothrombin time and INR were measured at follow-up visits every month. Regarding the 170 patients with prosthetic valves with a mean follow-up period of 2.44 years, 9 thromboembolisms (TE) were reported. The average TT and INR values in TE free patients among 101 in whom coagulability could be measured, were 21.1% and 1.73 respectively. The average TT and INR values in 5 patients with TE were 26.4% and 1.53 respectively and this was significantly (p < 0.01) higher (smaller) than in TE-free patients. 157 patients (mean age 55 +/- 12 y.o.) with various cardiovascular diseases (Table 2) were followed up for a mean of 4.9 +/- 3.2 years. As is seen in figure 4, mean INR values in TE patients were 1.28, in patients with bleeding complications 4.1, and in event free patients 2.07 respectively. In conclusion, with INR greater than 2.75, no thromboembolic complication occurred, but several hemorrhagic complications occurred at INR greater than 3. Therefore INR therapeutic ranges between 2.0-3.0 are recommendable both for the prevention of TE and bleeding complications. PMID- 8210750 TI - [Serum/tissue interleukin-6 concentrations and constitutional abnormalities in 4 patients with cardiac myxoma]. AB - Immunological features and the production of interleukin-6 (IL-6) in 4 patients with cardiac myxoma were studied. The patients' age ranged from 11 years old to 57 years old; all 4 patients were female. Case 1, an 11-year-old female patient with myxoma located in the right ventricle, was considered to be a familial case. Her mother had myxomas in the right and left atrium, and had undergone removal of both tumors 3 years before. Peripheral blood examination revealed various inflammatory parameters in all of these patients. White blood cell (WBC) count was over 8,000/cmm in 3 of the 4 patients, positive CRP was found in 2 patients, IgG was higher than 1,500 mg/dl in 3 patients, positive anti-nuclear antibody was seen in 1 patient, and positive rheumatoid factor was identified in 1 patient. The OKT 4/8 ratio of lymphocyte subpopulation was 4.65 in one patient. The lymphocyte mitogenic response to PHA was increased in 2 patients. Serum IL-6 increased in 3 of 4 patients, and returned to normal within 3 to 4 weeks after operation. The IL-6 concentration in the homogenized sample remarkably increased in all 4 patients. Tumors larger than 4 cm contained higher tissue IL-6 concentrations than those smaller than 2 cm. The cultured myxoma cells produced abundant IL-6 in the culture medium supernatant. We conclude that inflammatory signs and immunological abnormalities are common in patients with large cardiac myxoma, and, in addition, serum IL-6 levels may increase in such patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210751 TI - [The location and pattern of hypertrophy of the heart in hypertension and related hemodynamics by chest X-ray film]. AB - To answer questions where and how cardiac hypertrophy occurs, secondary to hypertension and in what state the underlying hemodynamics in the heart is when it develops, various cardiac parameters were measured in 132 patients with hypertension, including cardiothoracic ratio (CTR) as calculated on a posteroanterior view and interval (Y) between the inferior vena cava and posterior outline of the heart 2 cm above their cross section on a lateral view of chest X-ray films, Wezler's parameters of vascular dynamics, Blumberger's systolic time intervals and thickness of the interventricular septum and posterior wall as measured by cardioechography. The patients were divided into two groups by age, the young adult group including 62 ranging from 16 to 35 and the middle age group including 70 from 36 to 60. Association among these parameters were investigated by group. The results are as follows. 1. In the juvenile group, cardiac output was usually increased, and CTR was well correlated with septal thickness. In particular systolic pressure was significantly higher in patients with CTR of 50% or greater than in those with CTR less than 50%. As CTR increased, pre-ejection period (PEP) was prolonged, ejection time (ET)/PEP ratio decreased, stroke volume (Vs) and cardiac output (CO) tended to decrease, and peripheral vascular resistance (W) tended to increase. 2. In the middle-age group, Y was closely associated with thickness of the posterior wall. When the patients were divided into two groups by Y, diastolic pressure in patients having Y of 1.8 cm or greater was significantly higher than that in the rest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210752 TI - [Preoperative diagnosis of unroofed coronary sinus: a case report]. AB - A 54-year-old man was admitted to our hospital because of exertional dyspnea. A second heart sound with fixed splitting and a systolic ejection murmur along the left sternal border was audible. The chest roentgenogram showed increased pulmonary vascularity, and the electrocardiogram showed incomplete right bundle branch block. Two-dimensional echocardiography in the parasternal view demonstrated a partition defect between the left atrium and the coronary sinus. Furthermore, transesophageal echocardiography revealed a left-to-right shunt flow into the coronary sinus through the defect. At these points, the patient was diagnosed as having a partially unroofed mid-portion of the coronary sinus. Unroofed coronary sinus is a cardiac anomaly rarely diagnosed prior to surgical operation. Two-dimensional echocardiography, especially transesophageal echocardiography, is useful for the preoperative diagnosis of unroofed coronary sinus. PMID- 8210753 TI - [An autopsy case of the sinus of Valsalva aneurysm involved with tuberculous inflammation, leading to complete heart block]. AB - A case is presented of unruptured aneurysm of the non coronary sinus of Valsalva, causing involvement of A-V node and right coronary artery compression. The patient was a 68 year-old woman with a complaint of general fatigue. Electrocardiogram showed complete A-V block. Computed tomography showed an aneurysm of the non coronary sinus of Valsalva. A temporary pacemaker was implanted, but the patient developed respiratory failure and heart failure and died. At autopsy, macroscopically disseminated tuberculosis was noted in both lungs and kidneys. Microscopically a tuberculous inflammatory lesion extending into the A-V node was found. We report this rare case with some consideration of the literature. PMID- 8210754 TI - Morphometric model for pulmonary diffusing capacity. I. Membrane diffusing capacity. AB - The pulmonary diffusing capacity is related to the quantitative design characteristics of the pulmonary gas exchanger. The current model for estimating DLO2 from morphometric data breaks the diffusion path for O2 into four steps, three of which represent the membrane part of DLO2. A critique of this model on the basis of newer evidence leads to a modification of the model where the path from the alveolar surface to the erythrocyte membrane is considered as a single step. The structural determinant of this model for DMO2 is the ratio of effective diffusion surface to effective total barrier thickness. The effective surface is formulated as a fraction of the alveolar surface area, the most robust measure of lung design, whereas the effective barrier thickness is the harmonic mean distance--or mean proximity--between alveolar surface and erythrocyte surface. The methods for obtaining the morphometric measurements are discussed. The results show that the new morphometric estimates of DMO2 are 33% lower than those obtained with the old model, resulting in a reduction of the estimates of DLO2 by 10-20%. PMID- 8210755 TI - Blood gases, pH and hematology of montane and lowland coot embryos. AB - Blood gases, air cell-blood gas differences, blood pH, and hematology were compared in embryonic coots (Fulica americana peruviana) at 4150 m and sea level in Peru. Neither arterialized nor venous O2 tensions differed significantly between montane and lowland groups but blood CO2 tensions of the two groups differed significantly. The air cell PO2-arterialized blood PO2 difference of montane eggs was less than half the value in lowland eggs. Both arterialized and venous CO2 tensions differed substantially between montane and lowland groups. Despite these differences, plasma pH at both altitudes was statistically indistinguishable, due in part to variation in plasma [HCO3-]. Hematocrits of montane embryos were significantly higher than that of their lowland counterparts. PMID- 8210756 TI - Respiratory short-term potentiation (after-discharge) in elderly humans. AB - During a ventilatory stimulus, respiratory short-term potentiation (STP, after discharge) develops, so that ventilation after the stimulus is greater than that before the stimulus. When the stimulus is withdrawn STP gradually decays, tending to prevent hypoventilation and therefore stabilizing breathing pattern. STP has been demonstrated in young humans after brief hypoxic stimuli. Since respiratory arrhythmias increase with age, we examined the decay of STP in normal elderly humans (mean age 62), comparing them with young normals (mean age 27). Resting subjects were exposed to 35-50 sec hypoxia (end-tidal PO2 = 55 Torr) followed by hyperoxia and breathing analyzed during the hyperoxic period, when the subjects were also hypocapnic. With hypoxia, ventilation increased to 152% of control in both the older and younger subjects while end-tidal CO2 fell to 92.0% of control in the older subjects and 94.7% of control in the younger. In both groups the hypoxic increase in ventilation was almost entirely due to an increase of tidal volume. During hyperoxia, ventilation and tidal volume declined over 20-25 sec to control, pre-hypoxic levels, without an apparent undershoot, and there were no consistent differences between the older and younger subjects. Prolonging the hypoxic exposure to 90 sec had no influence on STP in the older subjects. We conclude that neither age nor prolonging the hypoxic stimulus from 50 to 90 sec influenced STP. PMID- 8210757 TI - Effect of sleep on changes in breathing pattern accompanying sigh breaths. AB - We studied the effect of sleep on the characteristics of sigh breaths and the associated changes in breathing pattern in breaths following spontaneous sighs in 4 unrestrained dogs with an intact upper airway. The sigh breath was characterized by its large tidal volume (VT), long TI and TE in comparison with the control breath. The volume of the sigh breath was larger in awake sighs than in those recorded during non-REM (NREM) and REM sleep. The strength of Hering Breuer reflex as determined by duration of the post-sigh apnea was similar in NREM and REM sleep. Sighs occurring during wakefulness, NREM and REM sleep were associated with augmented activity of the parasternal muscles during inspiration, and a persistent tonic abdominal muscle activity during the expiratory period. Breathing pattern in the post-sigh period was characterized by a smaller VT and longer TE in the first post-sigh breath in all sleep states (compared with the control breath), but the pattern returned to control level within the second or third post-sigh breath in both NREM and REM sleep. Sighs did not precipitate periodic breathing or other forms of abnormal breathing patterns in either wakefulness or sleep. We conclude that the respiratory control mechanisms stabilizing breathing after a sigh in the awake dog are intact in NREM and REM sleep. PMID- 8210758 TI - Transient ventilatory responses to endotoxin infusion in the cat are mediated by thromboxane A2. AB - We tested the hypothesis that ventilatory responses to endotoxin infusion in the anesthetized cat are mediated by thromboxane A2 (TxA2). Intravenous infusion of endotoxin (1.6 mg/kg of E. coli, strain 05:B55, delivered over 1 min) in six cats elicited increases in right ventricular blood pressure (Prv) and a transient systemic hypotension. These hemodynamic changes were accompanied by an abrupt apnea, followed by a transient period of rapid, shallow breathing, Cardiorespiratory changes coincided with large increases (> 10-fold) in the plasma concentration of TxB2, the stable metabolite of TxA2. These effects and the release of TxA2 did not occur if endotoxin was infused a second time into the same animal. In addition, animals that were pretreated with either indomethacin (n = 3; 3.0 mg/kg) or the TxA2 receptor antagonist, daltroban, (n = 4; 7.5 mg/kg) exhibited no change in Prv, arterial blood pressure, or respiration when given equivalent doses of endotoxin. We conclude that the release of TxA2 is responsible for the early pulmonary hypertension and rapid, shallow breathing observed during endotoxin infusion in the anesthetized cat. These TxA2-mediated responses are severe but transient in nature. PMID- 8210759 TI - Respiratory sensations in subjects who lack a ventilatory response to CO2. AB - An urge to breath is perceived during breath hold and hypercapnia (termed 'air hunger') and during heavy exercise (often termed 'shortness of breath'). To better understand the neural mechanisms responsible for these sensations we studied five patients (8-17 years old) with congenital central hypoventilation syndrome (CCHS) who lack ventilatory response to CO2. CCHS patients reported no respiratory discomfort during CO2 inhalation or during maximal breath hold which was of much longer duration than age-matched controls. However, all 3 CCHS patients who exercised heavily reported some sensations akin to shortness of breath (they increased breathing nearly as much as controls). Our results are consistent with two possibilities. First, the air hunger of hypercapnia and breath hold is caused by projection to the forebrain of respiratory chemoreceptor afferents which bypass the respiratory centers, while exercise shortness of breath is caused by direct projections of limb afferents or locomotory center activity. Second, air hunger and shortness of breath share the same origin- projection of increased brain stem respiratory center motor activity (corollary discharge) to the forebrain. PMID- 8210760 TI - Algebraic analysis of the determinants of VO2,max. AB - Considerable evidence exists to support the idea that maximum oxygen consumption in exercising mammals is determined by the quantitative interaction between diffusive and convective factors involved in the transport of oxygen between the environment and the muscle mitochondria. To complement experimental tests of this hypothesis as well as numerical modeling of the interaction between diffusion and convection, both in the lungs and tissues, this paper reports an analytical (algebraic) model of diffusive/convective interaction made possible by replacing oxygen by a hypothetical gas of similar effective solubility, obeying Henry's law. The model describes a homogeneous but potentially diffusion-limited lung arranged in series via the circulation with a homogeneous but potentially diffusion-limited muscle. Steady-state transport of gas through this system and its subsequent tissue utilization are described by three equations: (1) mass balance across the lungs, (2) diffusive transport across the lungs, and (3) diffusive transport in the tissues. The latter two equations involve interaction between diffusive and perfusive (convective) elements of gas transport. Independent variables in this analysis are inspired partial pressure, alveolar ventilation, cardiac output, effective solubility of the gas, and diffusing capacities of the lungs and of the tissues. Dependent variables are alveolar, arterial, and venous partial pressures and hence maximum O2 uptake by the tissues (VO2,max). Evaluation of this model in both normoxia and severe hypoxia is described. In normoxia, VO2,max is shown to be affected by all independent variables, but mostly by blood flow. However, in severe hypoxia, VO2,max, based on data from Operation Everest II, becomes more sensitive to muscle diffusing capacity and less so to blood flow. In normoxia, normal sea level values of the independent variables set VO2,max at a point where little further gain in VO2 would be seen without large increases in diffusive or convective properties. On the other hand, there is relatively little reserve, such that decreases in transport parameters would result in significant reductions in VO2,max. PMID- 8210761 TI - A stimulatory role of protein kinase C in feline tracheal submucosal gland secretion. AB - To determine the role of protein kinase C (PKC) in airway submucosal gland secretion, we examined the effect of a selective PKC stimulant, phorbol 12 myristate 13-acetate (PMA), on mucus glycoprotein (MGP) secretion, fluid secretion and intracellular Ca2+ concentration ([Ca2+]i) in isolated feline submucosal glands. MGP and fluid secretions were estimated by measuring trichloroacetic acid (TCA)-precipitable glycoconjugates and 22Na-efflux, respectively, from isolated glands. [Ca2+]i was measured using a Ca(2+)-sensitive fluorescent dye, Fura 2. PMA itself produced a significant increase in MGP secretion in a dose-dependent fashion (173% of control at 10(-5) M). PMA also produced a significant increase in 22Na-efflux (151% of baseline rate constant at 10(-5) M). Indomethacin failed to alter the increase in MGP secretion or in 22Na efflux in response to PMA. Two PKC inhibitors, 1-(5-isoquinolinesulfonyl)-2 methylpiperazine (H-7) and sphingosine, inhibited both MGP secretion and 22Na efflux stimulated by PMA; there was only a partial inhibition after stimulation by methacholine (MCh). PMA did not significantly alter [Ca2+]i and H-7 did not alter the MCh-induced [Ca2+]i rise. These findings indicate that PKC has a direct stimulatory role in stimulus-secretion coupling of airway submucosal gland secretion. PMID- 8210762 TI - Tone dependent nitric oxide production in ovine vessels in vitro. AB - We have determined the role of endogenous nitric oxide (NO) in regulation of vasomotor tone in ovine intrapulmonary and mesenteric vessels with resting tension and elevated vasomotor tone. Third generation intrapulmonary vessel rings and mesenteric vessel rings, 2-3 mm in diameter, were isolated from 20 sheep. NO production in the vessels was assessed by the change in tension induced by NG nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase. In vessels under resting tension, 10(-4) to 10(-3) M L-NAME induced a significant increase in tension only in veins but not in arteries. When tone was elevated with phenylephrine or U 46,619, a thromboxane A2 analogue, there was now a significant increase in tension in arteries with 10(-4) M L-NAME and in veins with 10(-5) M L-NAME. The increase in tension induced by L-NAME in veins was greater than that in arteries and greater when tone was elevated than under resting tension. Responses of pulmonary and mesenteric vessels were similar. Our data suggest that NO may play a role in regulating venous tone under baseline conditions and that the role of NO in regulation of vasomotor tone becomes more significant in the presence of nonspecific elevation of vasomotor tone in both arteries and veins. We speculate that endogenous NO production may be one mechanism by which pulmonary and systemic vessels counter the effects of vasoconstrictive agents. PMID- 8210763 TI - [Influence of the autonomic nervous system on the initial response of heart rate to active and passive orthostatism]. AB - Influence of the autonomic nervous system on the heart rate response to active and passive orthostatism. The purposes of this study were twofold. First, to compare heart rate responses as measured by R-R interval under two conditions of orthostatic stress, i.e. a change from supine to an active free standing-up position (active orthostatism, AO), and from supine to a passive 70 head-up tilt posture (passive orthostatism, PO) second, to utilize a standard pharmacological model to study the participation of the autonomic nervous system upon heart rate responses evoked by AO. In the first part of the research, eight healthy subjects (seven men, one woman) were evaluated for AO and PO. In both occasions, subjects were supine for 5 minutes and then adopted an upright or a tilted position in 3-5 seconds and remained motionless during 5 minutes. In the second part, eight men participated twice in the pharmacological studies. In day one, they stood up for control (AOC), after IV administration of atropine sulfate (0.04 mg/kg) (AO+atro) and after IV administration of propranolol hydrochloride (0.16 mg/kg) (AO+ATRO+PROPRA). In day two, subjects repeated the control AO (AOCII) and after the administration for propranolol hydrochloride alone. In the first study, AO was characterized by a fast shortening of R-R interval, which was maximal at beat 15th (relative tachycardia), followed by a rebound lengthening of R-R interval, reaching a plateau at beat 30 (relative bradycardia), demonstrating a biphasic response. PO was characterized by a small and gradual shortening of R-R interval without the biphasic responses of AO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210764 TI - [Laparoscopic cholecystectomy. First year experience at the Salvador Zubiran National Institute of Nutrition]. AB - The results at our institution with laparoscopic cholecystectomy in its first year are informed. The patients included in this study were routinely evaluated for an open procedure. The operation was done with the standard technique and equipment. In the postoperative period, ultrasound was done. Seventy-eight patients were included, 63 of them females. Age averaged 49.5 years (range 20 77). In three cases, choledocholithiasis was also demonstrated; these patients were treated with transendoscopic sphincterotomy. In 74 cases only cholelithiasis was demonstrated, two of them with shrinked gallbladder. In one case adenomyosis was found. Sixty-five cases had associated diseases which did not preclude the operation. Six cases were converted to an open cholecystectomy: two because of bleeding, the two cases with shrinked gallbladders, one with intrahepatic gallbladder, and the last one because of a Mirizzi syndrome with bile duct injury. In all cases, the conversion resolved the indication including the Mirizzi syndrome that required biliary reconstruction. No operative mortality was recorded. COMPLICATIONS: wound infection four, wound hematoma one, subhepatic hematoma two, and bile duct injury one. PMID- 8210765 TI - [Prevalence of antibodies to Pneumocystis carinii in subjects with high risk behavior for AIDS]. AB - P. carinii pneumonia affects more than 80% of patients with AIDS in developed countries. In Mexico this complication has been described in 12 to 23% of patients with AIDS, and it has been proposed that competitive disease such as TB and the low life expectancy of AIDS patients in Mexico are the possible explanations of this low percentage. However, in Mexico the frequency with which the population at risk of contracting AIDS is exposed to P. carinii is unknown. Therefore, we looked for P. carinii antibodies in a group of blood samples obtained in an AIDS detection center in Mexico City. A Western blot analysis was performed on 157 blood samples from homosexual and bisexual men and on 21 from female partners of HIV positive men. Positive results were obtained for 76.9% of the samples. No difference was observed in the frequency of P. carinii antibodies between HIV positive and negative individuals. Also, no differences by sex or age were found. Prevalence of P. carinii antibodies in this group is 76.9%, similar to that found in a comparable group in the U.S. PMID- 8210766 TI - [Molecular detection of chromosome Y DNA sequences in patients with Turner's syndrome]. AB - The presence of Y-chromosome material in the genome of phenotypic females has been associated with an increased risk of developing gonadal tumors. To assess whether DNA sequences of the Y-chromosome are present in the genome of individuals with gonadal dysgenesis and clinical features of Turner's syndrome, we have studied three patients with 45, X/46, X, + mar chromosome complement, and two Turner patients with 45, X/46, XY and 45, X karyotypes who served as positive and negative controls, respectively. Molecular detection of Y-DNA sequences was done by DNA-DNA hybridization using the specific probes pY97 and pDP1007 as well as by polimerase chain reaction. The results revealed that the marker chromosome of one of the patients contained DNA sequences from the centromeric region of the Y-chromosome in a manner similar to that found in the 45, X/46, XY patient and in the male control; the gene ZFY was negative in this patient, and was probably lost when the ring chromosome was formed. In contrast, the ring chromosomes of the other two patients did not exhibit the presence of Y-chromosome material. The results were interpreted as demonstrating the Y-chromosome origin of the ring marker in one patient with gonadal dysgenesis, and suggest an X-chromosome origin of the ring markers in the other two patients. These data further underline the relevance of practicing molecular studies in these disorders which may help to determine appropriate therapeutic strategies. PMID- 8210767 TI - Peripheral blood lymphocyte subsets and serum immunoglobulins in Sheehan's syndrome and in normal women during the menstrual cycle. AB - OBJECTIVE: There has been increasing evidence on the mechanisms underlying the interactions between the neuroendocrine and the immune systems, particularly in animal models with relatively few information in the human. In this study, we evaluate the cellular and humoral immunity in female patients with hypopituitarism and in normal women throughout the menstrual cycle in an attempt to determine the role of pituitary and gonadal hormones on the immune system. DESIGN: Serum immunoglobulins, peripheral blood lymphocyte subsets, and serum hormones were measured in eight patients with postpartum pituitary necrosis (Sheehan's syndrome) and in six normal women along different phases of the menstrual cycle, taking advantage of the lack of pituitary function and the cyclic variations in serum hormones, respectively. RESULTS: Patients with Sheehan's syndrome had higher T lymphocytes (CD2), including helper (CD4) and suppressor (CD8) cell subpopulations and B lymphocytes (CD19) when compared with normal menstruating women. An increase of serum IgA concentrations was also observed. Normal women showed little non-statistically different changes along the menstrual cycle in peripheral blood cell parameters and in serum immunoglobulin levels. CONCLUSIONS: a) Hypopituitarism in humans, in contrast with the animal model, may associate with immune up-regulation at both cellular and humoral levels; and b) hormonal changes along the normal menstrual cycle probably do not influence in great extent the immune system. PMID- 8210768 TI - [Renin: structure and expression regulation of the gene, biosynthesis, and cellular pathways of secretion]. AB - The renin angiotensin system plays a major role in the control of blood pressure and electrolyte balance. It consists of a cascade of proteolytic cleavages leading to the biologically active angiotensin II (AII). Renin acts on angiotensinogen to yield angiotensin I (AI). AI is a prohormone and must be cleaved to the octapeptide AII by the action of the angiotensin I converting enzyme. Application of recombinant DNA technology has made possible the cloning of the renin gene and its cDNA which has provided newer insights into the regulation of renin gene expression, biosynthesis, and secretion. The information gained from such molecular biology techniques may contribute importantly to the efforts in the development of an effective renin inhibitor for the treatment of hypertension. The mouse and rat renin gene contains nine exons separated by eight intervening sequences, in contrast the human renin gene contains ten exons separated by nine introns. However, the renin gene of the three species spans 12 kb approximately. In its 5' flanking region, major control elements are present which include promotors and enhancers as well as regulatory elements such as estrogen and glucocorticoid receptor sites, and cAMP induction sequences. The combined action of these elements will result in tissue specific expression and regulation of the gene. In addition to the control at the gene expression level, renin is also regulated at the post-translational and secretory levels. The translational product of renin mRNA is preprorenin, which is cotranslationally cleaved to prorenin, an inactive precursor of renin. The majority of the new synthesized human prorenin is constitutively secreted. However, prorenin is also processed intracellularly and converted to the mature single chain active renin which is stored in secretory granules. Active renin is released by a regulated mechanism which can be stimulated by cAMP and other secretagogues. Studies are under way to examine the responses of renin gene expression, biosynthesis and secretion to various physiological conditions and to determine if there are alterations in the structure and expression of the renin gene that may be involved in the development of clinical and experimental hypertension. PMID- 8210769 TI - Transport of amino acids into rat erythrocytes and its potential physiological role. AB - Previous studies have proposed the possibility that erythrocytes (RBC) are involved in the interorgan transport of amino acids; however, this role has not been confirmed. In order to study the likelihood that erythrocytes are involved in the interorgan transport, rates of influx and efflux of glycine, threonine, lysine, histidine and leucine were measured in rat red blood cells. Time course of influx of leucine, a large neutral amino acid, was very rapid (319 mumoles/L RBC. min), and a steady state was reached between 5 to 10 min of incubation, whereas glycine influx was very slow (5.04 mumoles/L RBC. min). Threonine influx was similar to leucine although the rate was slower (41.4 mumoles/L RBC. min); however, the steady state was reached in 30 minutes and its uptake showed less capacity. Histidine and lysine showed a continuous influx, and did not reach a steady state after 60 min of incubation. Efflux of leucine was extremely rapid indicating a rapid equilibration between the incubation medium and the intracellular space of the erythrocytes. Threonine efflux had a half life (t1/2) of between two to three min, independently of the medium used. Histidine showed a t1/2 of around six min, whereas for the small neutral amino acid glycine it was of 14 to 17 min. These results indicate that some large neutral amino acids are not involved in the potential interorgan transport by red blood cells due to the rapid equilibration of the concentration of amino acid between cells and the medium. PMID- 8210770 TI - [Immunoproliferative small intestinal disease. Report of a case with immunohistochemical and ultrastructural study]. AB - The clinico-pathological characteristics of a 22 years old mestizo mexican patient with immunoproliferative small intestinal disease (IPSID) are described. The patient coursed with chronic diarrhea, malabsorption, and a 30 kg weight loss. The laboratory tests revealed hypokalemia, hypocalcemia, hypoalbuminemia and decreased levels of immunoglobulins. The histological changes in the endoscopic biopsies included a dense lymphoplasmacytic infiltrate in the lamina propria that produced vellosity blunting and distortion of the crypts. The immunohistochemical analysis disclosed that almost every cell was positive to heavy chains and negative to light chains. The radiological studies showed thickening of the intestinal folds and mesenteric adenomegalies. In the full thickness biopsy of the yeyunum, in addition to the lymphoplasmacytic infiltrate, a high grade malignant lymphoma infiltrating the regional lymph nodes was documented. An ultrastructural study revealed viruses that resembled the morphology described for the Epstein-Barr virus. The main clinico-pathological findings of other eight mexican patients with IPSID previously reported are commented. It is concluded that the IPSID is a rare disease in our country but it can be found sporadically. PMID- 8210771 TI - Absence of HTLV-I infection in patients with malignancy in the Yucatan peninsula. PMID- 8210772 TI - A conceptual approach to placental pathology and pregnancy outcome. AB - This report focuses on the relationship of placental pathology to unfavorable pregnancy outcome. Relevant literature is cited and data from the author's investigations are reported and tabulated. The reader will find detailed information on placental lesions that have not been completely investigated or discussed previously. Particular considerations include placental meconium staining, edema, acute and chronic intrauterine infections, placental fetal vasculopathy with fetal nucleated red blood cells, and chorangiosis or other placental dysmaturity. These pathologic changes often signify the pathogenesis of cerebral palsy and other developmental disorders. Almost 90% of neurodevelopmental disorders are initiated before the intrapartum period. Prenatal asphyxia or severe chronic fetal hypoxia are probably present therein. Most investigations of these afflictions are invalid because they do not include placental study with well-designed epidemiologic methods. The pathologic placental findings that are most strongly associated with perinatal asphyxia include chronic ischemic changes, fetal nucleated red blood cells, intravillous hemorrhage, fetal fibrin vascular intimal cushions, meconium staining, and placental intervillous fibrin. Chorioamnionitis is a pathologic entity rather than a clinical syndrome as defined by obstetricians. When it causes severe prematurity, chorioamnionitis is also associated with cerebral palsy. PMID- 8210773 TI - Intrauterine death of a twin: mechanisms, implications for surviving twin, and placental pathology. AB - In multiple gestations, intrauterine death of one fetus occurs frequently. Sonographic studies indicate that many twin pregnancies are converted in early pregnancy to singletons. The "vanished" twin is sometimes recognized as a fetus papyraceous (compressus) incorporated into the placenta of the survivor. Death of one twin later in pregnancy may have serious implications for the survivor, especially in cases of monochorionic twins. One postulated mechanism has been that thromboplastic proteins from the dead twin are transfused into the survivor's circulation, resulting in disseminated intravascular coagulation. More recently it has been proposed that massive blood loss may occur from the survivor into the more relaxed circulation of a dead monochorionic twin through vascular anastomoses. These mechanisms may explain the higher frequency of cerebral palsy in monochorionic twins. These concepts emphasize the importance of careful examination and thoughtful interpretation of twin placentas. PMID- 8210774 TI - The placenta and viral infections. AB - Many viruses can infect the fetus in utero, by either ascending or hematogenous routes. Much is known about the maternal-fetal passage of virus from clinical, virologic, and serologic studies. Although transplacental passage is a key aspect of these infections, there is much more limited information about changes in the placenta. For a few infections, placental characteristics have been well described, and there is now increasing information on many others. Newer techniques for in situ demonstration of viruses will hopefully yield much information about diagnosis and the mechanisms of transplacental passage. PMID- 8210775 TI - Chronic villitis, chronic chorioamnionitis, and maternal floor infarction. AB - Chronic inflammatory infiltrates in the human placenta are much less common than acute inflammation. Most often, chronic inflammation is found in the villi (villitis), but rarely it may involve the fetal membranes. Villitis is associated with many well-documented maternal infections. Reviewed herein are features of the villous inflammatory infiltrate and associated villous changes that may suggest a specific bacterial or protozoal etiology. However, the majority of villitides are of unknown etiology. These may be the result of an unrecognized pathogen or, alternatively, may reflect an abnormal immune reaction. Chronic chorioamnionitis is commonly associated with villitis and has accompanied some well-documented viral, bacterial, and protozoal infections, but a specific infectious etiology is not identified in many cases. Maternal floor infarction is not a true infarct; it is characterized by the deposition of fibrin in the decidua basalis and intervillous space where enveloped villi become avascular and sclerotic. Maternal floor infarction is associated with intrauterine growth retardation and fetal demise. It frequently recurs in successive pregnancies. PMID- 8210777 TI - Placental thrombi and related problems. AB - The complex double circulation of the placenta adds diversity to the kinds of changes caused by thrombi and bleeding. Different lesions may have different clinical implications for the mother and fetus. The clinical history may be extremely important in directing the pathologic examination and in evaluating the significance of vascular lesions. PMID- 8210776 TI - The role of DNA flow cytometry in evaluation of partial and complete hydatidiform moles and hydropic abortions. AB - Knowledge of the nuclear DNA content of a hydatidiform mole is extremely useful in distinguishing a partial hydatidiform mole from a complete hydatidiform mole. Flow cytometry can be applied to both fresh or frozen tissue as well as to formalin-fixed, paraffin-embedded samples. Methodologies for extracting, staining, and analyzing nuclei are relatively simple and inexpensive, and results are accurate and reproducible. The vast majority of flow cytometers currently available or in use are more than adequate for distinguishing the large difference in nuclear DNA content between partial and complete hydatidiform moles, with sophisticated modeling programs and expensive equipment being unnecessary. We recommend that the DNA content of all hydropic placentas posing diagnostic dilemmas be analyzed by flow cytometry. When combined with clinical history and careful gross and microscopic examination, nuclear DNA content should serve as a very strong indicator of final diagnosis. PMID- 8210778 TI - Human Genome Project and cancer: the ethical implications for clinical practice. AB - The Human Genome Project has far-reaching implications for the entire spectrum of cancer care. An understanding of fundamental gene biology clarifies the role of genetics in cancer causation. The scientific advances of genetic screening for cancers have also given rise to problems such as employment and insurance discrimination, adverse psychosocial effects, and the ethical dilemma of "to screen or not to screen." PMID- 8210779 TI - Public health initiatives in cancer prevention and control. AB - Cancer-related health-care costs in dollars and in human lives are staggering. Reduction of cancer mortality depends largely on the access of the public to cancer prevention and control programs. Efforts by the federal government such as passage of the National Cancer Act and congressional appropriations have been important contributions. The national commitment to cancer prevention and control is evident through goals and programs of the National Cancer Institute, the Department of Health and Human Services, the American Cancer Society, and the Centers for Disease Control and Prevention. Prevention is also a focus of nursing organizations and industry. PMID- 8210780 TI - Commentary: expanding our horizons with an alternative approach to cancer prevention and detection. AB - In order to parallel the advances in cancer prevention science, nurses need to develop alternative approaches to viewing cancer prevention and cancer screening. An alternative cancer prevention model bases prevention and screening on the science of carcinogenesis. PMID- 8210781 TI - Breast cancer prevention and detection update. PMID- 8210782 TI - Cervix cancer prevention and detection update. PMID- 8210784 TI - Head and neck cancer prevention: the new challenge. PMID- 8210783 TI - Colon cancer prevention update. PMID- 8210785 TI - Lung cancer: prevention and detection update. PMID- 8210786 TI - Skin cancer prevention and detection update. AB - The best way to remedy the skin cancer epidemic is for the population to collectively practice primary preventive behaviors. However, many advances have been made in the areas of secondary and tertiary prevention, including the search for intermediate markers to facilitate skin cancer screening of high-risk groups and the use of chemopreventive agents in individuals with a history of high-risk lesions. PMID- 8210787 TI - Cancer risk and early detection assessment. AB - Nurses and physicians form an ideal corps for implementing cancer prevention and early detection efforts: providing health education, promoting health enrichment, defining high-risk groups and identifying patients who belong to them, and providing screening to ensure early diagnosis and prompt treatment. A personal medical history, a history of exposures in life-style, and a family history form the foundation for cancer risk assessment. The physical examination that follows takes into account the incidence and indications of cancer at various sites and the patient's risk profile. Health professionals can incorporate screening techniques into everyday practice by gathering information in the medical history, incorporating cancer detection in the physical examination, following up with more frequent screenings or referrals for those needing them, and becoming cancer detection advocates among patients and professional peers. PMID- 8210788 TI - Cancer prevention and early detection in ethnically diverse populations. AB - Providing cancer screening to the diverse minority subgroups of the United States is a challenge. In order to effectively screen the African American, Hispanic, Asian/Pacific Islander, Native American, Native Alaskan, and Native Hawaiian populations, cancer screening methods must be ethically and culturally based. Nurses must also strive make preventive care accessible to the underserved. PMID- 8210789 TI - Case management of the hospitalized patient receiving interleukin-2. AB - Patients receiving intermediate-dose CI rIL-2 therapy require hospitalization for assessment and management of the potentially severe side effects, primarily those involved with cardiopulmonary and renal toxicities. Once the tolerable dose level has been identified for a particular patient, the severity of the side effects on subsequent cycles of therapy may decrease. During therapy, nursing management includes interventions to minimize distressing side effects such as fever, flu like symptoms, fatigue, anorexia, and pruritus. Because the side effects of rIL-2 therapy are predictable, nurses can focus on early detection of these side effects and institute prompt interventions to reduce, minimize, or eliminate the symptoms. As oncology nurses prepare to care for hospitalized patients receiving rIL-2, a knowledge of the agent's side effect profile provides the foundation on which to base nursing practice. PMID- 8210790 TI - Nursing management of the nonhospitalized patient receiving recombinant interleukin-2. AB - Clinical trials have demonstrated that rIL-2 can be safely administered in an outpatient setting. A thorough nursing assessment ensures patient safety and effective toxicity management. Because it is becoming more economically advantageous to treat patients on an outpatient basis, nurses will need to become involved in all aspects of managed care. Outpatient administration of rIL-2 challenges nurses to be both technologically expert and clinically proficient. PMID- 8210791 TI - Nursing guidelines and discharge planning for patients receiving recombinant interleukin-2. PMID- 8210792 TI - Rationale and therapeutic basis for patients receiving recombinant interleukin-2. PMID- 8210793 TI - Nursing considerations for patients receiving biological response modifiers. PMID- 8210794 TI - Clinical pharmacological research with interleukin-2: implications for nursing. PMID- 8210796 TI - Radiographic signs and diagnosis of dental disease. AB - Dental radiographs are critical for the complete assessment and treatment of dental diseases. Dental radiography is commonly used to evaluate congenital dental defects, periodontal disease, orthodontic manipulations, oral tumors, endodontic treatments, oral trauma, and any situation where an abnormality is suspected. Although standard radiographic equipment and film can be used to produce dental radiographs, dental X-ray equipment and film provide superior quality images and greater convenience of animal patient positioning. An understanding of normal dental radiographic anatomy is important when interpreting dental radiographs. Stage III periodontitis is the earliest stage of periodontal disease at which radiographic abnormalities become apparent. Bone loss associated with periodontal disease can be classified as either horizontal or vertical. Periapical radiolucencies can represent granulomas, cysts, or abscesses, whereas periapical radiodensities may represent sclerotic bone or condensing osteitis. Lytic lesions of the bone of the jaw often represent oral neoplasms. Neoplasms also can displace or disrupt teeth in the dental arch. Resorptive lesions can be external or internal and appear as radiolucent areas involving the external surface of the root or the pulp cavity, respectively. Feline dental resorptive lesions, also known as odontoclastic resorptions, are a specific form of dental resorptive lesions unique to cats. PMID- 8210795 TI - Dental operatory design and equipment. AB - Improving and expanding the dental services of a practice can involve purchasing new equipment and even modifying or expanding the physical plant. Operatory design is important to the efficiency with which dental procedures can be performed. Equipment purchases to outfit the dental operatory should be made based on the specific needs and functions of a practice. PMID- 8210797 TI - Principles of dental extraction. AB - Despite major advances in the practice of veterinary dentistry during the past decade, extractions are still the most commonly performed dental procedures. A sound understanding of tooth root morphological and anatomic features is important to proper extraction. Tooth extraction techniques using sound surgical principles will permit efficient procedures, minimize trauma and discomfort to the animal patient, and encourage rapid healing. The keys to success are controlled forces and patience during the extraction process. PMID- 8210798 TI - Principles of endodontic therapy. AB - Endodontics is that branch of dentistry concerned with the treatment of damaged or diseased dental pulp. Veterinarians are now being asked to preserve tooth function and structure rather than to extract injured or diseased teeth. A variety of instruments are available that facilitate endodontic treatment. Endodontic treatment involves preparation (filing), sterilization, and obturation (filling) of the pulp cavity. Properly performed, endodontic therapy can effectively preserve dental structure and function. Complications of endodontic therapy will be discussed in "Problem Solving in Veterinary Endodontics" on page 165 in this issue. PMID- 8210799 TI - Problem solving in veterinary endodontics. PMID- 8210800 TI - Principles of restorative dentistry. AB - A great deal of information regarding materials, instrumentation, and techniques used for restorative dentistry can be borrowed from the human dental field. Veterinary restorative dentistry is in its infancy. A thorough knowledge of the commonly used materials and how they can be effectively applied is important. Treatment planning is probably one of the most critical phases of restorative dentistry as is painstaking attention to detail. If the guidelines for restorative dental techniques are followed, failures will be minimal. However, one of the most important points to remember is that the success of a restoration is not determined at the completion of the procedure. A restoration, if properly planned and performed, should last the lifetime of the animal patient. It is very important that veterinary dentists continue to evaluate and assess their restorative work at regular intervals so that restorative failures can be detected early, and so that restorative techniques and materials can be critically evaluated in veterinary patients. PMID- 8210801 TI - Feline dental resorptive lesions. AB - Resorptive lesions in feline teeth are frustrating. Despite a number of studies, there is as yet no satisfactory, clear-cut explanation for the cause, high prevalence, and recent emergence of this lesion, and experience with treatment has identified more problems, rather than indicated a successful management regime. PMID- 8210803 TI - Dental home care and preventive strategies. PMID- 8210802 TI - Systemic antimicrobials in the treatment of periodontitis in dogs. AB - Periodontitis is a common condition in dogs. Treatment of periodontitis consists of mechanical removal of plaque and calculus by scaling, root planing, and polishing the teeth. Antimicrobial therapy can provide additional improvement in severe or refractory cases of periodontitis when combined with dental prophylaxis if ongoing plaque control is not provided. The ability of various antimicrobials to reach therapeutic levels in the periodontal tissues differs greatly. The efficacy of antimicrobials against common periodontal pathogens also varies greatly. Choosing an appropriate antibiotic to treat periodontitis should be based on these considerations. Amoxicillin-clavulanate, clindamycin, and nitroimidazoles, such as metronidazole and tinidazole, seem to be particularly effective based on pharmacokinetic and clinical studies. PMID- 8210804 TI - Oral complications of cancer therapy and their management. AB - As the standards and client expectations for care of small animal patients with cancer increase, so does our awareness and understanding of the oral manifestations of complications associated with the treatment of these malignancies. This article has given an overview of some of the more common problems that can be anticipated when treating cancers, particularly those involving the head, neck, and oral cavity, and provided guidelines for the management of these problems when they do develop. In the future, as our management of these diseases becomes even more common, I would expect the veterinary dentist to play a vital role in the pretreatment evaluation, planning, and management of these animal patients. PMID- 8210805 TI - Renal development: challenge and opportunity. PMID- 8210806 TI - Renal developmental diseases. PMID- 8210807 TI - Glomerular blood flow. PMID- 8210808 TI - Biochemistry and genetic diseases of glomerular basement membrane. PMID- 8210809 TI - Research opportunities and future directions in glomerular disease. PMID- 8210810 TI - Predictions of things to come: acid-base regulation, chaos, and the molecular urologist. PMID- 8210811 TI - Interstitial macrophages. PMID- 8210812 TI - The nephritogenic T lymphocyte response in interstitial nephritis. AB - The work that has gone on regarding the development of nephritogenic T cells, their interactions with somatic structures in the kidney, and the vast biology that is engaged by their appearance are all amenable to study using the modern techniques of cellular and molecular biology. The models that have been developed to date illustrate common themes. The genes that encode for the effects of nephritogenic T cells operate by using the same general parameters as would be predicted for immune responses traditionally activated within the lymphoid compartment. Their immune response genes probably encode for structural proteins, some of which have been described, like the T cell receptor, T cell differentiation markers, MHC determinants, and cell-cell adhesion molecules. Maturation of nephritogenic T cell repertoires is fine-tuned by peripheral regulatory events and the cytokine bath produced by that microenvironment. Finally, CD8+ T cells that are programmed to damage the kidney can deliver signals which provoke phenotypically distinct patterns of injury. The future of research in this area holds great promise for developing a variety of new therapeutic modalities that involve antigen-specific regulation of nephritogenic T cell responses, control of cell-specific chemoattractants, modulation of cell cell interaction molecules, and the transcriptional attenuation of MHC class II determinants in somatic cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210813 TI - Nutritional influences on changes in kidney growth and function and the responses to kidney diseases. PMID- 8210814 TI - Modern renal biopsy interpretation: can we predict glomerulosclerosis? PMID- 8210815 TI - The continual reassessment method in cancer phase I clinical trials: a simulation study. AB - In cancer studies, the aim of phase I clinical trials is to identify an appropriate dose for experimentation in phase II and III studies. The continual reassessment method (CRM) has been developed recently and presented as the method of choice in the design and analysis of such phase I studies. However, to implement the method, some methodological and practical considerations must be addressed. This paper examines, through a simulation study, the sensitivity of CRM both to the initial modelling of the dose-toxicity relationship and the prior. It appears that the performance of CRM can be improved by using vague priors and initial tuning of the model to allow flexibility. PMID- 8210816 TI - On population and individual bioequivalence. AB - In a traditional assessment of the bioequivalence of two formulations of a drug one compares the average bioavailability from the two formulations. Anderson and Hauck argued that in some situations it is not sufficient to demonstrate average bioequivalence, and they proposed a method for the assessment of what they called individual bioequivalence, which essentially is the comparison of the individual responses to the two drug formulations within subjects. In this paper we propose a unified strategy for the assessment of bioequivalence that encompasses new approaches to the assessment of both population bioequivalence, which is the comparison of the marginal or population distributions of bioavailabilities, and individual bioequivalence, which is the comparison of the conditional or within subject distributions of bioavailabilities. The general idea is to use a comparison of the reference formulation to itself as the basis for the comparison of the test with the reference formulation. The new approaches overcome the main weakness of the current methods for the assessment of bioequivalence by considering the variability of bioavailabilities in addition to their means. The current methods for the assessment of bioequivalence, namely the conventional assessment of average bioequivalence and the proposal by Anderson and Hauck for the assessment of individual bioequivalence, emerge as special cases. One can evaluate the new bioequivalence criteria statistically by use of bootstrap confidence intervals. PMID- 8210817 TI - A note on the application of simple linear regression methods for trend detection at multiple sites and visits. AB - In comparing running median, tolerance, cusum, and regression methods for trend detection over a small number of visits, Yang et al. found that application of multiple Z-tests on the basis of a simple linear regression for each site separately was the most efficient for detection of trends at several sites simultaneously. Because the use of multiple Z-tests completely ignores the covariance among measurements taken from different sites, to improve the power we propose a global chi 2-test. Assuming the covariance matrix known, we have found that the proposed chi 2-test procedure is more powerful than multiple Z-tests for two-sided alternatives when both the correlation among measurements and the number of sites are small. We also have found that the former procedure can have power uniformly larger than the latter when ratios of slopes to standard deviations of measurements at different sites vary and the number of sites is large. In fact, in the latter situation, the proposed global chi 2-test procedure, usually used only for two-sided alternatives, can even have power larger than that of multiple Z-tests for one-sided alternatives. In the situation where the ratios of slopes to standard deviations of measurements are all equal, however, the proposed multivariate approach based on the chi 2-test distribution is the least efficient, especially when the number of sites and the correlation are moderate or large. Finally, to account for the effect of multiple tests over a series of visits on the overall alpha-level, on the basis of Monte Carlo simulations, we compute critical values for sequential use of the proposed multivariate test procedure. PMID- 8210818 TI - A Bayesian approach to logistic regression models having measurement error following a mixture distribution. AB - To estimate the parameters in a logistic regression model when the predictors are subject to random or systematic measurement error, we take a Bayesian approach and average the true logistic probability over the conditional posterior distribution of the true value of the predictor given its observed value. We allow this posterior distribution to consist of a mixture when the measurement error distribution changes form with observed exposure. We apply the method to study the risk of alcohol consumption on breast cancer using the Nurses Health Study data. We estimate measurement error from a small subsample where we compare true with reported consumption. Some of the self-reported non-drinkers truly do not drink. The resulting risk estimates differ sharply from those computed by standard logistic regression that ignores measurement error. PMID- 8210819 TI - Use of the Gibbs sampler to estimate transition rates between grades of coronary disease following cardiac transplantation. AB - Coronary occlusive disease following cardiac transplantation is monitored using serial angiography, and graded on a 3 point scale according to the amount of narrowing observed in major vessels. Disease progression is modelled as a continuous time Markov process. The Gibbs sampler is used to estimate the marginal posterior distributions of the transition rates between grades of disease and from each grade to death. PMID- 8210820 TI - An index of disease activity in rheumatoid arthritis. AB - This paper describes the Stoke Index which has been designed to give a global measure of disease activity in rheumatoid arthritis. The index is based on two objective laboratory measurements, one subjective and two semi-objective clinical measurements, chosen from 13 measurements using clinical judgement. Variable selection routines in principal components analysis are used to demonstrate that the index measures clinically defined disease activity. Its sensitivity and reversibility are also considered. A comparison is carried out with another index (Mallya-Mace) and a modification is suggested. PMID- 8210822 TI - A Bayesian strategy for screening cancer treatments prior to phase II clinical evaluation. AB - We address the problem of selecting a treatment for phase II evaluation when several candidate treatments emerging from phase I testing are available. A pre phase II Bayesian selection design which randomizes patients among treatments is proposed. The patient group in the trial has prognosis more favourable than that of phase I patients but less favourable than the target group of the subsequent phase II trial. The patient response rate distribution in each treatment arm is continually updated during the trial for comparison with early termination cutoffs, and the best final treatment must satisfy a minimal posterior efficacy criterion. The primary aim is to replace the usual informal treatment selection process with a fair comparison formally based on a combination of prior opinion and clinical data. PMID- 8210821 TI - Analysis as-randomized and the problem of non-adherence: an example from the Veterans Affairs Randomized Trial of Coronary Artery Bypass Surgery. AB - In most randomized clinical trials not all patients adhere to the therapy to which they were randomly assigned. Instead, they may receive the therapy assigned to another treatment group, or a therapy different from any prescribed in the protocol. When non-adherence occurs, problems occur with the analysis comparing the treatments under study. Rigorous statistical principles require attributing outcome events to the original random treatment assignment ('intent-to-treat' analysis). Using data from the Veterans Administration Cooperative Study of Coronary Artery Bypass Surgery, we report the intent-to-treat analysis and apply four other methods of analysis for analysing non-adherers: 1. exclude non adherers from analysis; 2. transfer them to the alternative treatment group at the time of randomization; 3. censor them at the time of treatment change, and 4. transfer them to the alternative treatment group at the time of treatment change. Inherent problems and biases of these four other methods are discussed. PMID- 8210823 TI - A comparison of the power of two tests for qualitative interactions. AB - 'Qualitative' or 'crossover' interactions arise when a new treatment, compared with a control treatment, is beneficial in some subsets of patients and harmful in other subsets. We present a new range test for crossover interactions and compare it with the likelihood ratio test developed by Gail and Simon. The range test has greater power when the new treatment is harmful in only a few subsets, whereas the likelihood ratio test has greater power when the new treatment is harmful in several subsets. We provide power tables for both tests to facilitate sample size calculations for designing experiments to detect qualitative interactions and for interpreting the results of clinical trials. PMID- 8210824 TI - Applications of extraction mapping in environmental epidemiology. AB - This paper discusses a new method which allows the extraction of a background disease rate from a data set consisting of spatial co-ordinates of morbidity or mortality events. We demonstrate its application with two data sets, one based on cancer registry data and the other on death certificates. PMID- 8210825 TI - Design effects for binary regression models fitted to dependent data. AB - Dependent data, such as arise with cluster sampling, typically yield variances of parameter estimates which are larger than would be provided by a simple random sample of the same size. This variance inflation factor is called the design effect of the estimator. Design effects have been derived for cluster sampling designs using simple estimators such as means and proportions, and also for linear regression coefficient estimators. In this paper, we show that a method to derive design effects for linear regression estimators extends to generalized linear models for binary responses. In particular, some simple expressions for design effects in the linear regression model provide accurate approximations for binary regression models such as those based on the logistic, probit and complementary log-log links. We corroborate our findings with two examples and some simulation studies. PMID- 8210826 TI - Visual and statistical assessment of spatial clustering in mapped data. AB - Maps have seen increasing use to examine regional variation in health, but there has been little research on the visual perception of spatial patterns in mapped data. Theories of graphical perception suggest that the interpretation of maps is complex relative to other types of graphical material. This paper describes an experiment in which observers assessed a series of maps with respect to their amount of clustering. Maps with various types of spatial pattern were visually distinguishable; comparisons between variants of the same map, however, using different shading and plotting symbols indicated that the method of data representation also had a strong effect on visual perception. There was some evidence for a learning effect in complex maps. The relationship between the visual assessments and a statistical measure of spatial autocorrelation was significant but imperfect. PMID- 8210827 TI - Combining independent studies of a diagnostic test into a summary ROC curve: data analytic approaches and some additional considerations. AB - We consider how to combine several independent studies of the same diagnostic test, where each study reports an estimated false positive rate (FPR) and an estimated true positive rate (TPR). We propose constructing a summary receiver operating characteristic (ROC) curve by the following steps. (i) Convert each FPR to its logistic transform U and each TPR to its logistic transform V after increasing each observed frequency by adding 1/2. (ii) For each study calculate D = V - U, which is the log odds ratio of TPR and FPR, and S = V + U, an implied function of test threshold; then plot each study's point (Si, Di). (iii) Fit a robust-resistant regression line to these points (or an equally weighted least squares regression line), with V - U as the dependent variable. (iv) Back transform the line to ROC space. To avoid model-dependent extrapolation from irrelevant regions of ROC space we propose defining a priori a value of FPR so large that the test simply would not be used at that FPR, and a value of TPR so low that the test would not be used at that TPR. Then (a) only data points lying in the thus defined north-west rectangle of the unit square are used in the data analysis, and (b) the estimated summary ROC is depicted only within that subregion of the unit square. We illustrate the methods using simulated and real data sets, and we point to ways of comparing different tests and of taking into account the effects of covariates. PMID- 8210828 TI - An empirical Bayes approach to the estimation of the incidence curve of HIV infection. AB - A new approach is proposed for estimating the incidence curve of HIV infection and obtaining short term prediction of AIDS incidence. It is based on the method of back calculation which utilizes the fact that AIDS incidence is generated from HIV infection incidence by convolution with the incubation period distribution, but avoids the difficulties associated with approximating the infection incidence curve by a class of step functions. Instead, the infection incidence is modelled as a simple stochastic epidemic process which ensures smoothness of the estimate. We first derive the distribution of AIDS incidence knowing infection incidence. The best linear estimators of infection incidence as well as future AIDS incidence are given; a smoothed past AIDS incidence is also obtained. The parameters of the stochastic infection process can be estimated by maximum likelihood using a normal approximation to the marginal distribution of the AIDS incidence. This approach is applied to AIDS incidence data in the United States up to mid 1987. We find that the epidemic started in mid 1976, peaked at the end of 1983 and dropped afterwards. PMID- 8210829 TI - Influence of model-building strategies on the results of a case-control study. AB - We evaluate the analysis of a case-control study in which many variables were investigated simultaneously. The purpose of the study was to explore some rather unspecific hypotheses about potential risk factors for adult brain tumour. Our aim is to show that in the analysis of case-control studies many decisions are necessary which are usually not published in detail. As in most studies these decisions are made during analysis and are data dependent. We demonstrate that the data allow sensible alternative decisions which influence the final results. A sensitivity analysis of several aspects of the analysis such as different measurement scales, variable selection, handling of missing values and interactions was performed, and demonstrated variation in the results based on the strategy for analysis. We conclude that details of the final analysis should be decided in the planning phase of a case-control study, and that more details of model-building strategies must be published. Results from a study where the analysis is highly data dependent must be interpreted with caution and validation of the results with new studies is essential. PMID- 8210830 TI - Comparison of methods for the analysis of longitudinal interval count data. AB - Longitudinal studies are often concerned with estimating the recurrence rate of a non-fatal event. In many cases, only the total number of events occurring during successive time intervals is known. We compared a mixed Poisson-gamma regression method proposed by Thall and a quasi-likelihood method proposed by Zeger and Liang for the analysis of such data, in the case where the mean was correctly specified, using simulation techniques with large samples. Both methods produced similar standard errors in most situations, except in the case of time-dependent covariates with non-Poisson-gamma data where they were seriously underestimated by the Thall method. A simple method for discriminating between the variance forms of the two methods is described. The findings are applied to the analyses of clinical trials of non-melanoma skin cancer and familial polyposis. This study extends the findings of Breslow concerning variance misspecification in overdispersed Poisson and quasi-likelihood models to the longitudinal setting. PMID- 8210831 TI - How to establish equivalence when data are censored: a randomized trial of treatments for B non-Hodgkin lymphoma. AB - Interest in equivalence trials has been increasing for many years, though the methodology which has been developed for such trials is mainly for uncensored data. In cancer research we are more often concerned with survival. In an efficacy trial, the null hypothesis specifies equality of the two survival distributions, but in an equivalence trial, a null hypothesis of inequivalence H0 has to be tested. The usual logrank test has to be modified to test whether the true value r of the ratio of hazard rates in two treatment groups is at least equal to a limit value r0. If prognostic factors have to be taken into account, the Cox model provides tests of Ho, and a useful confidence interval for the adjusted relative derived from the regression parameter for the treatment indicator. An equivalence trial of maintenance therapy was carried out in children with B non-Hodgkin lymphoma, and serves as an illustration. PMID- 8210833 TI - Etiology of bladder cancer. AB - That the etiology of bladder cancer involves environmental factors is well documented. Most chemical carcinogens probably affect the urothelial cells via their presence in the urine. As an important cofactor, cell-proliferative activity may be increased by urinary bladder infection, irritation by bladder stones or through the action of a variety of direct acting chemicals or agents. Among the known causative factors, avoidable major ones are occupational exposure to certain chemicals such as benzidine and 4-aminobiphenyl, cigarette smoking, and bilharzial infection, which could be eradicated by a combination of praziquantel, antihelminth therapy, education, and improvements in social welfare. An anticarcinogenic drug, cyclophosphamide, used as an immunosuppressive agent also seems to be associated with a high risk of idiopathic induction of bladder cancer and physicians should therefore pay particular attention to its diverse effects when considering its prescription. In contrast to the above, the consumption of coffee and tea containing artificial sweeteners is now thought unlikely to be a major risk. So far there is no good biochemical tool to predict individual exposure to bladder carcinogens/or relative risk of bladder-cancer development. However, acetylation capacity can be applied to assess susceptibility to carcinogenic amines in people exposed in their working environment. Progress in molecular-biological analysis will hopefully bring to light etiology-specific DNA damage in bladder tumors, and it may prove useful for prediction of tumor behavior in the near future. PMID- 8210832 TI - The use of simulation in the design of two cardiovascular survival studies. AB - Simulation has become practical as an everyday tool given the wide availability of high performance workstations. We argue that simulation can play an important role in determining the number of patients required in a survival study, particularly if the assumption of proportional hazards does not hold, or if the study design is complex. The argument is illustrated by two examples. The first considers the design of a post myocardial infarction survival trial in which the hazard ratio is not constant. The second provides sample size estimates for a multicentre heart failure study in which both the treatment effect and the control mortality rate vary across centres. PMID- 8210834 TI - The natural history of superficial bladder carcinoma. PMID- 8210835 TI - Biological markers of prognosis in transitional cell carcinoma of the bladder: current concepts. PMID- 8210836 TI - DNA flow cytometry: an update of its use in assessing prognosis for transitional cell cancer of the bladder. PMID- 8210837 TI - Image analysis in superficial transitional cell carcinoma of the bladder. PMID- 8210838 TI - Computer modeling and decision making: clinical applications in bladder cancer. PMID- 8210839 TI - [Science, non-science and false science]. PMID- 8210840 TI - [Acute hepatic insufficiency. Diagnosis, treatment and results following orthotopic liver transplantation]. PMID- 8210841 TI - [Administrative involvement in hospital information systems]. PMID- 8210843 TI - [Clinical aerosol therapy in pneumology: advantages and drawbacks of equipment and techniques]. PMID- 8210842 TI - [Memory function in elderly persons]. PMID- 8210844 TI - [Dermatological treatment and pregnancy]. PMID- 8210845 TI - [A case of Ollier's disease]. PMID- 8210846 TI - [Ergospirometry and pneumological practice]. PMID- 8210847 TI - [What is your roentgen diagnosis? Chronic subdural hematoma]. PMID- 8210848 TI - [Music therapy and internal medicine]. AB - Since December 1988 the district hospital of the Oberwallis hosts the 4 year project "Music-Therapy in Internal Medicine" under the scientific guidance of Dr. H. H. Decker-Voigt, director of the Institute of music therapy of the musical academy Hamburg. This therapy can be described as a form of psychotherapy which uses the medium music with its particularities as an adjunct for treatment. The different levels of action of music, a functional and a regressive one and their respective importance for music therapy are described first. An introduction to the two forms of music therapy, the receptive and the active with their respective particularities follows. Indications for music therapy are by large not disease-specific but depend on the assessment of the importance of psychic components in somatic disease. Coping with disease, psychosocial integration and promotion of positive resources or self-healing potential are regarded as indications for music therapy. Music therapy is not indicated when the patient is not motivated or his stay at the hospital is shorter than 2 weeks. We offer a music therapy to all patients in whose illness, according to our evaluation, emotional and psychic factors play an important role and to those patients with functional disorders on whom we would like to learn more by the psychoanalytic possibilities of music therapy. According to our experience music therapy is well suited as an adjunct in many diseases in internal medicine and represents an enrichment of our therapeutic possibilities. PMID- 8210849 TI - [Misdiagnosis of psychosomatic disorders]. AB - Considering the frequency with which the diagnosis 'psychosomatic illness' is established, it is puzzling how little attention has been paid to its differential diagnosis. The reason for this may be found not only in the difficulties with which that diagnosis is made but also in the doctor's view of the world and his or her understanding of illness in general. If the doctor only believes in what can be measured and weighed as being real, all symptoms for which no identifiable cause can be found must be considered as imaginary and 'all in the patient's head'. Most contemporary theories about the origin of psychosomatic illness are based on Freud's speculations, established at the beginning of this century. The are deeply rooted in the mechanistic, reductionistic and monocausalitic theories typical for his time. They suggested that the metamorphosis from thought-processes to somatic symptoms begin with a rather mysterious 'jump', taking place in the unconscious of the patient and thus remaining unknown to him. Today we know that all illness has a multifactorial basis and does not develop in a straight line but as a cybernetic loop. Psychosocial factors play as much a role as biological ones. Diagnosis by exclusion (no clear physical findings) or through dualistic thinking (the cause must be either psychological or physical) are, after inadequate knowledge of somatic or psychological medicine, the most common source of the erroneous diagnosis of psychosomatic illnesses. To avoid this, a psychosomatic perspective is needed, an outlook which is based on a holistic understanding of man in health and sickness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210850 TI - [Interaction of the world of dreams and wakefulness]. AB - While we are dreaming the dream is the world. This reality is extinguished when we wake up. At the same time we recognize parts of the world of wakefulness in the things we dreamed about. Both worlds merge, and each in doing so interprets the other. Interpreting dreams is like drawing out these perspectives. This is shown here with examples from a series of dreams. They are woven into the biography of the dreamer and continually transform the traces of his world. The illustrations serve to visualize the elements of the world of wakefulness and of history, which reappear in a changed form in the dream. PMID- 8210851 TI - [Dying and the concept of death in Paracelsus' perspective]. AB - The views of Paracelsus about dying and death found on medical, philosophic and christian religious argumentation. Two visualizations using different solutions can be shown: a natural way as teleologic principle, a supernatural one in the horizon of eschatology. PMID- 8210852 TI - [Death and dying in medieval times]. AB - Out of the complex theme a specific phenomenon is chosen which most likely can be assigned to the appearance of the plague in Europe in the late medieval times: 'the dance of death' mainly in its artistic, particular graphical expression. To this intent the 2600 originals of the Dusseldorf University collection are used. The prerequisites for this novel art are discussed: the sudden outbreak of the plague in Italy 1347/48, the precursors of the legend about the three living and the three dead, the so-called 'transitoriness poems', the 'Conflictus literature' and other ideas about symbolism of death in classical antiquity and early christianism are opposed to the dances of death. The latter and confrontation of the various classes and professions with the merciless death over the following centuries is used with many examples to show the changing views up to the present times. The strong religious component subsides slowly in the Baroque to a more extroverted depiction. The Age of Elightment presents yet other pictures than the 19th and 20th century where death is confronted with still new professions and events, also from technical domains. Medicine and the physicians play an important role in this from the beginning on. The question after the memento mori remains for the mortal. PMID- 8210853 TI - [Encounter of self and the world in mourning]. AB - Mourning is a process following a certain course. It permits us to part with something that was of great value for us. By mourning we do not only express our sentiments evoked by this loss but we reorient ourselves by the expressed emotion of an interrelating self to an individual one. Thereby mourning is a process of reflection on the essence of a relationship that has been lost but that still acts in us. It means reflection on ourselves and our interaction with the environment and those things in our lives that support. PMID- 8210854 TI - [The patient with chronic low back pain in a thermal spa]. AB - We have made our study over a period of five months. Out of 553 patients admitted to the Thermal Clinic at Lavey-les-Bains, we observed 111 patients suffering from chronic low-back pain, noting the changes, both subjective and objective, during their three-week stay at the clinic. From the physical aspect, they were encouraged to increase lumbothoracic mobility. From the subjective aspect, an evaluation of pain and handicap level, was made using a visual comparison scale and the completion of a questionnaire. We concluded that, in the short term, thermal treatment resulted in an appreciable relief of pain for these patients. In the long term, however, in view of the changing developments in clinical measuring techniques it is not possible to estimate in advance the functional effectiveness of treatment. PMID- 8210855 TI - [Functional therapy of Achilles tendon rupture]. AB - We are going to present two cases with functional treatment of Achilles tendon ruptures. We define a treatment as functional if the involved limb is either not immobilized at all or whenever the immobilization is incomplete and for a limited time only and when no operation is necessary. The functional treatment is presented as an alternative, and we are going to present the advantage and disadvantage. PMID- 8210856 TI - [Acute upper gastrointestinal hemorrhage in a 63-year-old alcoholic]. PMID- 8210857 TI - [Diarrhea]. AB - A 50-year-old female patient complained about watery diarrhea for two weeks. Because of back pain nonsteroidal antirheumatics had been prescribed for months before. The endoscopic and radiologic investigation demonstrated a large gastrocolic fistula due to NSAID-induced gastric ulceration and an acid-induced colitis in the transverse colon. Treatment consisted in partial gastric resection and resection of the transverse colon. PMID- 8210858 TI - [A case from practice (277). Creatine kinase increase following unusual physical exertion]. PMID- 8210859 TI - [Triple concentrated load against HIV virus]. PMID- 8210860 TI - [What is your roentgen diagnosis? Cardiogenic pulmonary edema in masked pneumonia]. PMID- 8210861 TI - [Psychopharmacological models of drug dependence. Key role of the dopaminergic mesolimbic system]. AB - The potential of a compound to induce drug dependency may be described as an interaction of its positive reinforcing and its discriminative as well as its aversive properties. Environmental factors and conditioning play thereby important, modulating roles. Drugs of abuse act via central mechanisms which mediate basal sensations such as reward and satisfaction. Neurochemical and neuroanatomical investigations suggest a key role of the dopaminergic mesolimbic system in these processes. Addictive drugs from several pharmacological classes have in common to stimulate the dopaminergic mesolimbic system, albeit by different mechanisms. However, other non dopaminergic neurotransmitter systems, e.g. the GABAergic, the opioid or the serotonergic system, are also involved in drug-seeking behaviour. PMID- 8210862 TI - [What is your diagnosis? Pulmonary sarcoidosis (stage II/III) with bone manifestations (Osteitis cystoides Jungling)]. PMID- 8210863 TI - [Should the obligation to feed continue until death?]. PMID- 8210864 TI - [Is man what he eats?]. AB - The statement 'man is what he eats' was coined by Ludwig Feuerbach (1804-1872), thus emphasizing the worldliness of human nature as a challenge to the general concentration on the life after and the religious belief of his time. Both views surely reflect only one side of the truth, since the intake of food not only grants man his material survival, but offers him also values of culture, friendship, and of partaking in the divine, for which he strives in his innermost heart. PMID- 8210865 TI - [Needs of caregivers and needs of the dying regarding food]. AB - The need for food in dying patients varies from one individual to the next. This requires the nursing staff to establish a precise history of the eating and drinking habits of these patients and their families. The necessary care is based on this history, on the professional knowledge of the nursing personnel, and on the ethical guidelines of the Swiss Association of Nursing Personnel, published in 1990. Care and nutrition programs must be reevaluated daily and adapted to the changing situation of the patient. The paper presents six major strategies drawn up by Brown and Chekryn in 1987 in order to assist nursing staff in coping with dehydration problems. Five (non-representative) interviews with experienced nurses throw light on the importance of giving special consideration to the nutritional needs of dying patients. PMID- 8210866 TI - [Feeding and hydration--an unphysiological answer to the problem of dying]. AB - A short description of the physiological changes caused by dehydration and lack of calories is followed by a framework of guidelines that could provide a basis for care dying patients beyond mere mitigation of suffering. It is derived from the observation of the laws that we perceive to govern the processes of birth and death, living and dying. Polarity and the inherent rules of human developmental changes are defined as perpetually valid aspects of wisdom and are set off against the perpetually changing frontiers of knowledge with their limited validity. In conclusion, we submit an outline of our practical efforts in dealing with dying patients at the Affoltern Bezirksspital. PMID- 8210867 TI - [Should the obligation to feed continue until death? Evaluation of the problem from the legal viewpoint]. AB - In accordance with the nowadays prevailing opinion, the right of existence and the penal protection of human life in general subsist independently of the sense and value ascribed to them by a third. Correspondingly, the dying, the patient with an apallic syndrome and the neonate with grave neural defects are entitled to protection of life and basic nursing. To these belongs--among others--the right of nutrition. If a discerning patient refuses (artificial) nutrition no-one respecting his will can be considered criminally liable. If there is no such expression of intent, it is admissible to stop--if necessary step by step--the patient's artificial nutrition, because doing so represents help in the final stage of his life. This proceeding implies that the patient does not disagree with such a renunciation (permissible passive euthanasia). In the case of patients with apallic syndrome and neonates with grave neural defects who are--in the doctor's opinion--not in the dying phase, stopping (further) nutrition is permissible solely--and only in this case--if this does not constitute the main reason for the patient's death. PMID- 8210868 TI - [Ethical aspects of the problems of nutrition of terminally ill patients]. AB - This contribution deals initially with the question whether or not the problem to be solved is an ethical one and, if so, wherein the ethical controversy consists. Following that, the wide spectrum of cultural significances of food and eating is outlined. In a last part, the limits of normative management are pointed out. The positive contribution of ethical thinking is not so much to be seen in setting up rules but in conveying fundamental attitudes which enable us to let our actions be governed by wisdom. PMID- 8210869 TI - [What is your diagnosis? Continuous hemicrania]. PMID- 8210870 TI - [liver and pregnancy]. PMID- 8210871 TI - [Sexual assault: could the perpetrators not be identified more often?]. AB - Sex crimes represent an important category of crimes. Physicians have to deal with them when treating victims in the emergency room. Forensic scientists, on their side, try to collect any trace of physical contact between victim and aggressor (sperm, fibres, etc.). But their success is largely dependent on the quality of the first intervention. Crucial evidence can be damaged or lost. Collaboration between physician and forensic scientist is essential when dealing with sex crimes to provide victims with the medical care they need, while using every piece of evidence which will allow the identification of the authors. PMID- 8210872 TI - [Autologous tumor therapy]. AB - The dermatologist from Munich developed three differently called therapies; however, they basically show the same theory. They are the treatment with transoptin, tumor identification training for autologous immunocompetent cells (TI-TAI), and the autologous target cytokine (ATC) therapy. The ATC therapy is supposed to have a positive effect on all cancers and immunodeficiencies. Side effects are denied, although oncologists have noticed fatigue, fever, pain, lymphopenia, leukocytosis and others. The dermatologist supposedly establishes tumor cell and leukocyte cultures from blood and mixes them later on. The cytokines (ATC), produced by the lymphocytes, are harvested in 40 ampules and then subcutaneously injected. One cycle with the ATC therapy costs around 3000 DM. The dermatologist believes that tumor cells can only be immunologically identified during the dividing phase. He stimulates the cultured tumor cells to divide. At the same time he adds the autologous immunocompetent cells which should be trained to identify tumor cells and to produce cytokines. The dermatologist uses many terms unconventionally and imprecisely. The in-vitro training of lymphocytes for tumor defense with the method of the dermatologist is experimentally unproven. The production of the ATC preparations is kept secret. Also unclear are the mechanisms of action and the clinical efficacy. Besides neologisms, the dermatologist does not offer any scientific or clinical facts for his therapy of cancers. PMID- 8210873 TI - [Antibiotic-resistant pneumonia]. AB - A 77-year-old lady with malaise, cough, weight loss, an elevated ESR and bilateral patchy infiltrates on the chest X-ray is described. The symptoms progressed inspite of antibiotic treatment. On the basis of clinical findings, transbronchial biopsy, bronchoalveolar lavage and lung function tests the diagnosis of a bronchiolitis obliterans, organizing pneumonia (BOOP) was established. The clinicopathological entity of BOOP, its differential diagnosis and treatment are discussed. PMID- 8210874 TI - [A case from practice (278). Familial polycystic kidney disease, adult type: increasing kidney insufficiency. Renal hypertension. Renal anemia]. PMID- 8210875 TI - [What is your diagnosis? Synovial cyst of the elbow]. PMID- 8210876 TI - [Multiresistant tuberculosis in Switzerland--a new problem?]. PMID- 8210877 TI - [Tuberculosis: diagnosis and incidence of resistance 1991/92]. AB - In the past few years new diagnostic strategies have considerably cut down the turnaround time for detection, identification and susceptibility testing of mycobacteria. Highly sensitive methods (e.g., gene probes, PCR, gas liquid chromatography/mass spectrometry) will further improve rapid and accurate laboratory testing. They which all aim at a direct detection of mycobacteria in clinical specimens. In a brief survey conducted by the NZM/IMM susceptibility data of M. tuberculosis isolates in Switzerland were obtained from 14 laboratories. As expected, the great majority of the strains exhibit full sensitivity against the primary antituberculous drugs. The patterns as well as the percentages of resistance for the period between January 1991 to June 1992 do not differ significantly from the results obtained in an earlier investigation. PMID- 8210878 TI - [Multiresistant tuberculosis in the Zurich Hohenklinik Wald from 1984 to 1992]. AB - Out of a total of 386 patients with culture-proven tuberculosis, ten cases of multidrug-resistant tuberculosis were treated in a high altitude chest clinic in Switzerland between 1984 and 1992. Two patients, Swiss, were alcoholics, the other eight foreigners. None of the patients were HIV-positive. Both Swiss had primary INH resistance, then developed secondary INH/RMP resistance due to poor compliance. All patients were treated with at least two additional in-vitro sensitive drugs as well as with INH. Five patients underwent resection of lung parenchyma. One of these patients has had three operations and remains the sole therapy failure. One patient died before an operation could be performed. All others are well. Possible reasons for multidrug-resistance and the management of the ten cases are discussed in accordance with the literature. PMID- 8210879 TI - [Incidence of resistance of tuberculosis bacteria in Switzerland]. AB - Based on a survey, results on resistant tubercle bacilli in Switzerland during October 1987 through April 1991 are presented. In 94% of 2482 tuberculosis cases reported, susceptibility testing results have been available. The radiometric BACTEC technique was used in 76%. Resistance was detected radiometrically for INH in 7%, for rifampin in 1.9% and for ethambutol in 0.7%. The age-specific resistance among Swiss was 12% in the youngest and 3% in the oldest age group. In patients from South American and from Far Eastern countries, INH and rifampin resistance was the highest. Resistance was found in 5.7% of the Swiss and in 7.5% of all. In addition, suggestions for the surveillance of resistant tubercle bacilli have been made. PMID- 8210880 TI - [Multiresistant tuberculosis in New York]. AB - New Yorkers have to deal with a tuberculosis situation which is of greater extent and a health-care system which is less prepared than in the sixties. Poverty and the HIV epidemic have had a negative impact on the control of tuberculosis. The emergence of nosocomial multidrug-resistant tuberculosis has created an explosive situation. In 1991, rifampin resistance was 33% in patients who had received antituberculosis therapy and 10% among the patients who had never been treated. PMID- 8210882 TI - [Prof. Geiser--a satirist?]. PMID- 8210881 TI - [Disseminated tuberculosis with a multiresistant strain of Mycobacterium tuberculosis in an HIV-infected Swiss male]. AB - Multidrug-resistant M. tuberculosis in HIV-infected people has not yet been reported in Switzerland, and there have been no nosocomial epidemics as they have recently occurred in the USA. We present the case of a 38-ear-old HIV-infected man who developed disseminated tuberculosis as AIDS-defining disease. Initially he was treated with isoniazid, pyrazinamide and rifampin. Due to the emergence of resistance to isoniazid and streptomycin, ethambutol was added for one month. Later the therapy was changed back to the initial three drugs. The patient responded well to this therapy, but five months later developed a relapse. In addition to the originally diagnosed double-drug resistance, a reduced susceptibility to rifampin appeared. Ethambutol, ciprofloxacin and amikacin were added to the original three-drug regimen. This resulted in rapid clinical improvement, although sputum cultures remained positive for M. tuberculosis two months later. This isolate was resistant to pyrazinamide. For that reason pyrazinamide was replaced by clofazimine. 14 months after diagnosis the patient died of hepatic failure. Because there was a delay in isolation of one week, 37 potentially exposed health care workers were tested by the Mantoux skin test. No conversions were observed. This case report demonstrates that tuberculosis in HIV infected patients in Switzerland may be caused by multidrug-resistant M. tuberculosis. We propose that until the results of a susceptibility assay are known, a four-drug combination should be used initially in this patient group. PMID- 8210883 TI - [What is your roentgen diagnosis? Enostotic osteoma eburneum (compact vertebral osteoma). Intervertebral chondrosis L5/S1 and generalized spondylosis of the lumbar vertebrae]. PMID- 8210884 TI - [Minimally invasive surgery in the treatment of extrauterine pregnancy]. AB - Of 147 patients operated by endoscopy, 86 (59%) were treated conservatively by linear salpingotomy or tubal aspiration and 61 (41%) were treated by salpingectomy. One patient with a history of bilateral salpingectomy had a cornual implantation and was also successfully treated by laparoscopic technique. There were no intraoperative complications. In eight patients (4.5%) with postoperative complications, a second operation was performed because of persistent trophoblast and/or hemorrhage. Six patients were treated by laparoscopic salpingectomy. All complications were associated with conservative treatment and typically occurred with a delay of up to 23 days. In six of these instances, the surgeon was rather inexperienced in laparoscopic operation. After an average follow-up time of 22 months, the pregnancy rate was 68%, of which 73% were intrauterine pregnancies. Laparoscopic treatment of ectopic pregnancies has proven to be an effective and safe procedure even at a teaching hospital. Since all complications occurred after conservative treatment this data suggests that salpingectomy should be the treatment of choice in ectopic pregnancy, whereas linear salpingotomy should only be performed when specially indicated. PMID- 8210885 TI - [Coffee and caffeine. Various selected aspects for everyday practice]. AB - Moderate consumption of methylxanthines, for example in coffee, tea, cola-drinks and other foodstuffs containing caffeine, is probably without particular health risks, insofar as other risk factors (smoking, alcohol, nutrition in general) can be kept under control. To avoid prohibition on one hand and to evaluate necessary restrictions concerning caffeine consumption individually on the other hand is an artful task in daily medical practice. Coffee is one of the chemically most complex consumables, and its physiologic effects are accordingly complex and to a great deal still unknown. Caffeine in moderate amounts has practically neither a negative effect on health nor does it promote pathogenesis of disease. Only excessive use may induce problems. Therefore, excessive use of caffeine is assumed in those persons, in which withdrawal is followed by withdrawal symptoms (41). Many aspects of caffeine and biomedical caffeine effects cannot yet be explained. Nevertheless, from the medical point of view, there are no objections to a moderate use of caffeine with one exception: if the coffee break is used as a pretext for smoking. PMID- 8210886 TI - [Drug-induced calculi]. AB - Drug-induced urinary calculi are rarely observed. However, it is useful to know this etiology. A complete anamnesis of drugs and dosages is mandatory if a patient presents with lithiasis, since some pharmacotherapies may carry an enhanced lithogenic risk. The list of lithogenic drugs is discussed. In order to yield preventive data, infrared, spectrophotometry is the best available analytic method. PMID- 8210887 TI - [Anemia, thrombopenia and kidney failure as a sequela to aortic valve replacement]. PMID- 8210889 TI - [A case from practice (279). 1. Chronic fatigue syndrome (CFS). 2. Psychosocial problems]. PMID- 8210888 TI - [Tetanic equivalents, cephalgia, absences]. AB - Real hypoparathyroidism may develop after surgery of the thyroid, more rarely of the parathyroid. The idiopathic form is thought to be connected with autoimmune processes. We present the case of a female patient with acquired hypoparathyroidism after strumectomy 40 years ago. A clinical picture, not only with neurologic and dermatologic manifestations but also late organic sequelae of chronic hypocalcemia, i.e. calcification of basal ganglia, had developed impressively. Without the proof of laboratory tests diagnosis is difficult to establish at the first go in medical practice, since clinical symptoms may be few or widely scattered. Since the rate of strumectomies has dropped as a consequence of restricted indications, acquired hypoparathyroidism has become rarer. A simple long-term treatment with vitamin D and calcium relieves the patient from tetanic problems and prevents severe and irreversible late organic lesions. PMID- 8210890 TI - [Review of anatomy and physiology of the vestibular system]. PMID- 8210891 TI - [Equilibrium]. PMID- 8210892 TI - [Vertigo of peripheral origin]. PMID- 8210893 TI - [Neurological approach to vertigo]. PMID- 8210895 TI - [Diabetes: a disease with multiple intervening parties]. PMID- 8210894 TI - [Physiotherapeutic treatment of vertigo]. PMID- 8210896 TI - [Dysfunction of the pancreatic beta cells observed in non-insulin-dependent diabetes]. PMID- 8210897 TI - [Factors responsible for fasting hyperglycemia in the non-insulin-dependent diabetic patient]. PMID- 8210898 TI - [Physiopathology of chronic complications of diabetes]. PMID- 8210899 TI - [How should an obese diabetic patient be treated?]. PMID- 8210900 TI - [Diabetes and terminal renal insufficiency: statement of failure or reflection on the caregiving function?]. PMID- 8210901 TI - [Functional performance of patients with rheumatoid arthritis and arthroplasty of the hip and knee. Apropos of 19 cases]. PMID- 8210902 TI - [Blast injuries]. PMID- 8210903 TI - [The concept of a coordinated health care network of The Riviera]. PMID- 8210904 TI - [The "Greek miracle" in medicine. Justification of a thesis]. PMID- 8210905 TI - [Trauma pathology of the wrist in the family practitioner's office]. PMID- 8210906 TI - [Dermatological molds of Jules Baretta (end of the 19th century)]. PMID- 8210907 TI - [Regarding the article "Diagnosis of senographically suspect but clinically occult lesions: anatomopathological study". by Claude Yves Genton, Rev. Med. Suisse Rom., 113: 451-454, 1993]. PMID- 8210908 TI - Liver cancer surgery. PMID- 8210909 TI - Surgery for small liver cancers. AB - During the last 16 years, we have resected small hepatocellular carcinomas (HCCs) measuring 5 cm or less from 362 patients, 266 of whom also had liver cirrhosis. The operative and hospital mortality rate were 1.7% and 1.9%, respectively. These showed a gradual decrease year by year in parallel with reduction of intraoperative blood loss achieved by the selective vascular occlusion technique and Pringle method. In 1989, 87% of hepatectomy patients were discharged without the need for whole blood transfusion, and 5-year survival was 43.7%. Tumor size, number of tumors, intrahepatic metastasis, vascular invasion, and capsular invasion were significant prognostic factors. Edmondson grade and the operative procedure employed were significantly related to outcome. Our standard policy for selection of operative procedures and perioperative care is described, and the selection of treatment modalities is discussed. PMID- 8210910 TI - Experience with resection of segment VIII of liver for hepatocellular carcinoma. AB - Hepatic segment VIII is located at the dome of the right liver lobe, next to the intrahepatic inferior vena cava (IVC) and is situated between the right and the middle hepatic veins. Its close relation to the IVC inferior medially makes liver cancer resection in this particular segment extremely difficult and hazardous. A personal series of 32 cases of segment VIII resection for hepatocellular carcinoma performed during the period January 1970-May 1992 is being presented. Most resections could be performed with occlusion of the porta hepatis only but some cases required total hepatic vascular exclusion. Since segment VIII is surrounded by major vessels, the extent of resection is limited in this region. Furthermore, tumor cells are easily disseminated along the vascular route. The long-term results are far from ideal. One-, 3-, and 5-year survival rates were 93.33%, 57.14%, and 28.5%, respectively. However, eight patients in this series have survived 180, 168, 104, 78, 53, 43, 43, and 36 months, respectively, and some of them have returned to work. Therefore, despite the technical difficulties involved in segment VIII resection, it is still worthwhile adopting an aggressive operative approach to this group of patients. PMID- 8210911 TI - Cryosurgery of liver cancer. AB - Cryosurgery, the in situ destruction of tissue using subzero temperatures, has been used to treat hepatic metastases. Because it is a focal treatment, cryosurgery can be used in patients with unresectable lesions due to location (next to major blood vessels) or multiplicity. In this study, 57 patients with unresectable hepatic metastases were treated with cryosurgery (with at least a 6 month follow-up). The number of lesions treated ranged from 1-16 with a mean of 4.6. Forty-three patients (73%) had bilobar disease, while 25 patients (42%) were treated with a combination of resection and cryosurgery. The disease-free survival rate (patients with normal computed tomography [CT] scans and carcinoembryonic antigen [CEA] levels) was 27% with a mean follow-up of 21 months. This is comparable to other hepatic cryosurgery studies that have found survival rates of 25-37.5%. Although the results are still short-term, this study indicates that hepatic cryosurgery offers the hope of long-term survival in patients with unresectable hepatic metastases. PMID- 8210913 TI - Rehepatectomy of primary liver cancer. AB - From January 1960 to July 1991, 72 patients underwent reoperation for recurrence of liver cancer. Hepatectomy was performed twice in 59 cases, three and four times each in nine and three cases. The 1, 3, and 5-year survival rates after the first operation were 98.6%, 69.9%, and 49.5%, respectively, while after the second operation these rates were 90.8%, 53.5%, and 36.1%, respectively. The 1,2, and 3-year survival rates after the third operation were 100%, 85.6%, and 36.7%, respectively. The preliminary results of rehepatectomy are thus encouraging. The indications for reintervention, types of operation, prophylactic measures against tumor recurrence and metastases, and evaluation of rehepatectomy are discussed. PMID- 8210912 TI - Microwave surgery in the treatment of hepatocellular carcinoma. AB - Microwave surgery was employed for the treatment of 50 patients with hepatocellular carcinoma (HCC) and liver cirrhosis, including hepatectomy in 46 patients and in situ coagulation of tumor in 4 patients. In the study, 2,450 MHz microwaves were generated and transmitted to a monopolar needle electrode. For hepatectomy, the needle electrode was inserted into the liver parenchyma to coagulate the liver tissue and this was repeated at 1 cm intervals along the line where incision is anticipated. For unresectable HCC, the needle electrode was directly inserted into HCC to coagulate the cancer in situ. The average amounts of blood loss and blood transfusion for 46 hepatectomies using microwave were 215 +/- 189 ml and 274 +/- 261 ml, respectively. Eighteen patients (39.1%) did not need blood transfusion. A significant lower volume of blood loss and blood transfusion was observed in comparison with 46 matched conventional hepatectomies, 652 +/- 1,008 ml and 841 +/- 878 ml, respectively, all being P < 0.01. There were no operative mortality and complications, such as delayed bleeding, bile leakage, and abdominal infection. These results indicate that microwave surgery can be utilized safely and effectively in the field of liver surgery. PMID- 8210914 TI - Evaluation of preoperative transcatheter arterial embolization in the treatment of resectable primary liver cancer. AB - The effects of preoperative transcatheter arterial embolization (TAE) and intra arterial injection of Lipiodol were retrospectively evaluated in patients with resectable hepatocellular carcinoma experienced during two different periods of time. In the TAE study, there were 31 patients with TAE and 107 patients without TAE. In the Lipiodol study, 60 patients had received Lipiodol injection and 68 patients served as controls. Curative hepatic resection was performed in all cases. As such preceding treatments had been performed at other hospitals, two comparing groups were fairly randomized in both the TAE and the Lipiodol study. Preoperative TAE did not influence the postoperative morbidity and mortality rates, cause of late death, and long-term survival rate in overall patients, but seemed to produce a better survival in noncirrhotic patients. Antitumor effect by Lipiodol injection was found in that the cancer free survival rate was significantly better in the group with Lipiodol injection. However, the overall 5 year survival rate was significantly better in the group without Lipiodol (67%) than in the group with Lipiodol (26%). The present study may indicate that preoperative TAE or Lipiodol injection should not be routinely performed. Such treatments may produce a substantial benefit only in selected patients with good hepatic functional reserve. PMID- 8210915 TI - Postoperative chemoimmunotherapy for the treatment of liver cancer. AB - A randomized study using spleen-derived lymphokine-activated killer (LAK) cells in hepatocellular carcinoma (HCC) is reported. We induced cytotoxic lymphocytes from resected spleen of HCC. The effect of recombinant interleukin-2 (rIL-2) activated spleen cells for prevention of recurrence of HCC after hepatic resection was studied. Enough mononuclear cells could be harvested from the resected spleens. The induction of activated spleen cells was carried out by culture in fresh medium containing 1,500 JU/ml of IL-2. The cytotoxicity of the activated spleen cells maintained high levels during the culture period ranging from 3-30 days. These autologous activated spleen cells were administered to patients 2 days after the intra-arterial infusion of Adriamycin. A randomized study using these spleen LAK cells resulted in lower recurrence rates in the LAK IL-2-treated group. No severe side effects were observed. The lymphocytes derived from resected spleens were useful as the source of effector cells in clinical adoptive immunochemotherapy for HCC, because of their higher cytotoxicity and the simplicity of gaining a large amount of cells. PMID- 8210916 TI - Role of liver transplantation in the treatment of hepatocellular carcinoma. AB - The results obtained by liver transplantation (TX) (n = 105) for hepatocellular carcinoma (HCC) were compared with those achieved by hepatic resection (HX) (n = 76). Overall 1- to 5-year survival rates after TX were 66%, 49%, 39%, 36%, and 36%, and those after HX were 71%, 55%, 47%, 37%, and 33%, respectively. The survival rates after TX and HX correlated well with pTNM stages, and the overall survival rates were similar in each stage between the TX and the HX group. However, when HCC was associated with cirrhosis of the liver, the survival rates after TX were significantly higher than those after HX at each stage of pTNM classification. Tumor recurrence rate was high both after TX (43%) and HX (50%), particularly in stage IV-A. Tumor recurrence rate was significantly lower after TX than after HX in HCCs of stages II and III. Liver TX has established its definite role in the treatment of HCC, particularly in the presence of hepatic impairment or cirrhosis of the liver. PMID- 8210917 TI - Comparison of hepatic resection and transplantation in the treatment of liver cancer. AB - One hundred twenty cirrhotic patients underwent hepatic resection (n = 60) or transplantation (n = 60) for hepatocellular carcinoma. Overall 3-year survival and survival without recurrence were 50% and 23% in the resection group compared to 47% and 44% in the transplantation group. Several characteristics of the tumors have been studied in order to determine prognostic factors in both groups. Thus, results for 3-year survival without recurrence following transplantation in patients with tumors < 3 cm/one or two nodules (83%) were superior to those following transplantation in patients with tumors larger than 3 cm or three or more nodules (37%) (P < 0.02) and to those following resection (10%). Thus, for patients with small tumors, until now the best candidates for resection, transplantation appears to have significantly better results. Conversely, for larger lesions, with three or more nodules, transplantation, in view of the critical donor situation, is probably not indicated. PMID- 8210918 TI - [The history of Revue Neurologique]. PMID- 8210919 TI - A comparison of the efficacy of etodolac SR (Lodine SR) and etodolac (Lodine) in patients with rheumatoid arthritis or osteoarthritis. AB - The efficacy and safety of a sustained-release (SR) formulation of etodolac were compared with those of conventional etodolac in two separate, randomized, double blind, multicenter, 6-week trials. This report presents an interim analysis of the data from these studies. One study included 174 patients with rheumatoid arthritis (RA): 58 received etodolac SR 400 mg once daily (q.d.), 59 received etodolac SR 600 mg q.d., and 57 received etodolac 200 mg twice daily (b.i.d.). The second study included 230 patients with osteoarthritis (OA): 80 patients received etodolac SR 400 mg q.d., 76 received etodolac SR 600 mg q.d., and 74 received etodolac 300 mg b.i.d. Efficacy was evaluated by physician's global and patient's global assessment (both studies), number of painful joints (RA study), number of swollen joints (RA study), pain intensity (OA study), and weight bearing pain (OA study). The interim analyses of the data from the studies indicates that all three regimens produced significant improvements from baseline in all mean efficacy values at each assessment; there were no significant differences between the treatment groups. The incidence of study events, except for dyspepsia, was comparable among the treatment groups in each study; dyspepsia occurred at a significantly lower rate in patients treated with etodolac SR than in patients treated with the conventional formulation of etodolac. We conclude that etodolac SR is as effective and safe as conventional etodolac for the treatment of patients with RA or OA. PMID- 8210920 TI - Meta-analysis of three double-blind comparative trials with sustained-release etodolac in the treatment of osteoarthritis of the knee. AB - A meta-analysis was done with the final data from three trials that provided the first results relating to efficacy and safety of the new sustained-release (SR) formulation of etodolac versus established nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of osteoarthritis (OA) of the knee. The studies were 4 week, double-blind, randomized, parallel-group comparisons of etodolac SR 600 mg (119 patients) against diclofenac SR 100 mg (54 patients), tenoxicam 20 mg (46 patients), or piroxicam 20 mg (18 patients). The primary efficacy parameters (assessed after 2 and 4 weeks of treatment) were physicians' and patients' overall assessments of patients' condition, night pain, and pain intensity. All patients had radiographic and clinical evidence of OA of the knee. For the meta analysis, the data from the individual etodolac SR studies were pooled and compared with the pooled data for diclofenac SR, tenoxicam, and piroxicam. The homogeneity of the treatments across studies and the changes from baseline between groups were tested using a Cochran-Mantel-Haenszel test and an analysis of variance, including "study," "treatment," and "center within treatment" effects and their interaction. The analysis for the efficacy parameters was based on the final assessment during therapy (last visit). At baseline, the two treatment groups were comparable. Improvement rates were high in both groups (range, 68-81%), indicating that treatments were effective for most patients. No significant treatment difference was observed for the patients' overall assessment, night pain, or pain intensity. Both etodolac SR and the reference preparations were well tolerated. No clinically significant changes were noted in the laboratory data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210921 TI - Meta-analysis of two double-blind comparative studies with the sustained-release form of etodolac in rheumatoid arthritis. AB - A meta-analysis was done with the data from two studies that provided the first efficacy and safety results for the new sustained-release (SR) formulation of etodolac versus established nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis (RA). The studies were 4-week, double-blind, multicenter, randomized, parallel-group comparisons of etodolac SR 600 mg (102 patients) with either diclofenac SR 100 mg (65 patients) or piroxicam 20 mg (35 patients). The data for etodolac SR were pooled and compared with the pooled data for the comparators. The primary efficacy assessments (weeks 2 and 4) were physician and patient overall evaluation of the patient's condition, number of painful/tender joints, and number of swollen joints. Patients met at least five of the American Rheumatism Association diagnostic criteria and were within Steinbrocker progression stage I, II, or III and functional class I, II, or III. The homogeneity of the treatment groups across studies and the changes from baseline between groups were tested using a Cochran-Mantel-Haenszel test and an analysis of variance including "study," "treatment," and "center within treatment" factors and their interaction. The efficacy analysis was based on the final assessment during therapy (last visit). The patients in the etodolac SR group were older than those in the comparators group (P = 0.032), and there were more patients over 65 years of age in the etodolac SR group than in the comparators group (31% versus 14%, respectively; P = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210922 TI - Pharmacokinetics of sustained-release etodolac. AB - Etodolac exhibits linear pharmacokinetics, good oral bioavailability, greater than 99% protein binding, a low oral clearance (almost exclusively non-renal), a relatively small volume of distribution and a half-life that averages 7.3 +/- 4.0 h. No significant pharmacokinetic differences have been noted in patients with mild to moderate renal impairment, in patients with cirrhosis, in the elderly or in patients with arthritis. The pharmacodynamics of the drug are well characterized in terms of pain intensity differences (PID) yielding an EC50 of 13 micrograms/ml. The extensive kinetic/dynamic characterization of etodolac, together with its short half-life, makes the drug an ideal candidate for a sustained-release (SR), once-a-day formulation. Etodolac SR formulations exhibit the same pharmacokinetic characteristics as the conventional-release (CR) formulation, except for a longer time to peak concentration and a lower peak concentration. Fluctuation ratios upon multiple dosing are comparable for equal total daily doses of etodolac SR and twice-daily doses of the CR formulation. Administration with food (high-fat meal) did not affect areas under the curve for either the CR or the SR product. Simulation analyses for etodolac SR suggest that PID responses are maintained over 24 h. PMID- 8210923 TI - The safety profile of sustained-release etodolac. AB - The safety profile of a new sustained-release (SR) form of etodolac was evaluated in 539 young and elderly patients with osteoarthritis or rheumatoid arthritis. Four long-term, open-label studies were conducted in nine different countries totaling 3,827 patient-months' exposure to etodolac SR. Patients were treated with either 400 mg or 600 mg etodolac SR once a day for up to 52 weeks. Withdrawals due to adverse reactions were low, occurring in only 5% (26/539) of all patients. The most common drug-related study events were GI-related, occurring in < 8% of patients. Elderly persons (> or = 65 years of age) were not at greater risk for adverse reactions or drug-related study events than were younger patients. Serious GI-related study events were rare (0.2%). The low level of serious GI effects was consistent with a separate study measuring gastrointestinal (GI) blood loss. Etodolac SR produced significantly less GI blood loss than naproxen in normal subjects. Because of its favorable safety profile, etodolac SR can serve as an alternative to conventional etodolac, providing the convenience of once-daily administration. PMID- 8210924 TI - Worldwide experience with etodolac (Lodine) 300 mg b.i.d. in the treatment of osteoarthritis. AB - Worldwide experience with the conventional formulation of etodolac (300 mg b.i.d.) was reviewed in 12 randomized, double-blind, parallel-group studies in patients with osteoarthritis (OA) of the hip or knee. The studies were conducted in 13 countries at 59 sites, and 1289 patients were enrolled. The results of 9 comparative and 3 placebo-controlled clinical studies were examined to compare the efficacy and safety of etodolac versus piroxicam, naproxen, indomethacin, indomethacin sustained-release (SR), and diclofenac SR. Efficacy assessments were made at pretreatment screening, baseline, and every 2 weeks thereafter during treatment until study completion up to 4, 6, or 8 weeks. The primary efficacy assessments were the patient's and physician's global evaluations, pain intensity and night pain, or joint tenderness and walking pain. Safety was assessed with reference to study events, reports of laboratory results, and vital signs measurements. Patients in all active treatment groups showed prompt response to therapy. According to the physicians' global evaluation, at least 64% of all etodolac-treated patients and 62% of all active-reference preparation-treated patients had improved by the end of the study. Similar results were seen in the patients' global evaluation. All of the study drugs were well tolerated. Eight (8%) percent of the etodolac-treated patients withdrew because of study events. The proportions of patients treated with active reference preparations and placebos who withdrew because of study events ranged from 3% to 18%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210925 TI - The "blind alley". Its significance for evolutionary theory. AB - Several scientists have apparently independently used the term "Blind Alley" to indicate that major evolutionary change has ceased. The failure to observe speciation through selection would indicate that obligatory sexual reproduction is incapable of producing progressive evolution. Favoring this conclusion is the evidence that sex determination has independently evolved and may be further correlated with the equally nonhomologous evolution of contemporary gametic sources in the same animal groups. To incorporate these facts into a meaningful theory demands the postulate of a presexual mode of reproduction which has been suggested as identical with the first meiotic division. A hypothetical scenario for macroevolution is presented. PMID- 8210927 TI - [Air contaminants]. PMID- 8210926 TI - Stability of arbitrary structures. Its implications for heredity and evolution. Part I. AB - I designate the stance of seeking, in biological processes, essential isomorphism with the phenomena encountered in the human mind, reverse-reductionism, from which I expect to find an alternative way of reconstructing biology. From the axiom that structure (relationship among components) is arbitrary as is known from the Saussurean linguistic theory, it follows that relevant structures in various living processes are potentially multiple rather than unique. Moreover, a structure may take more than one configuration, whose transition should be conceived as transformation. However, structure itself is stable, or invariant by definition, and not subject to transformation. Both structure and its configurations are hereditary in the sense that they bind, with necessity, biological processes including genetic constitution. Such an invisible structure can be maintained dynamically over generations through the constraints imposed on the survival of organisms. Many characters, including genes, in an organism are only cryptically held, and may come to be manifested under certain unusual environmental conditions. Evolution is viewed as configurational transformations and emergence of new structures: once a structure emerges, all of its possible configurations are logically laid down, at the very outset, to channel the future course of its evolution, whose materialization, however, is a matter of contingency. PMID- 8210928 TI - [Asthma induced by aspirin and arachidonic acid metabolites. I. In search of answers to an enigma (first part)]. AB - Acetylsalicylic acid, one of the most commonly used drugs and high on the list of causes of drug reactions. Since early publication on 1902 by Hirschberg, a great deal of information has emerged on aspirin sensitivity, including data on epidemiology, further characterization of the two major subtypes of sensitivity (bronchospastic and urticarial types), hereditary aspects, cross-reactions to other nonsteroidal antiinflammatory drugs, and methods of desensitization. Although the pathogenesis of aspirin-sensitive asthma remains unknown, several theories has been proposed to explain the disease enigma. PMID- 8210929 TI - [Pilomatrixoma (calcified epithelioma of Malherbe). Report of a case and brief review ot the literature]. AB - A case of a upper extremity pilomatrixoma (calcifying epithelioma of Malherbe) clinically confused with a secondary reaction to the dog antigen application presented in a young woman and diagnosed following surgically excised is presented. On cytologic examination, basaloid cells, multinucleated giant cells and deposits of calcium were identified. Adjacent to the basaloid cells were acellular masses suggestive of ghost cells. PMID- 8210930 TI - [Anaphylaxis and urticaria caused by exercise. Review of the literature and report of 2 cases]. AB - Urticaria is a common pathology, yet, urticaria induced by physical agents represent 17% of urticaria cases, they are more frequent in adolescents and young adults. Exercise may induce anaphylaxis, urticaria, asthma and rhinitis. This first two pathologies are not so usual. The incidence of cholinergic urticaria (CU) is five to seven percent. this incidence of anaphylaxis induces by exercise has not been described. It is very difficult to clinically distinguish CU and EIA, establish criteria are described in the paper. There are two clinical forms of CU; local and systemic. The ideal diagnostic methods was the ID methacholine test. Antihistaminics are the treatment of choice, together with tolerance induction by progressive exercise. Two typical cases of CU are presented as they occurred at the Allergy and Clinical Immunology Service of Hospital Infantil de Mexico, Federico Gomez. PMID- 8210931 TI - [An anticipatory and prospective scheme for the treatment of the asthmatic patient]. AB - Asthma is a chronic disease, that require familiar education and advisement in order to get control. The records of 71 asthmatics children were studied, the ages ranged from 6 months to 16 years, both sexes were included. All of them came up to the allergologic outpatient section at IMSS regional hospital located in Ciudad Madero, Tamaulipas. All cases reviewed in 1992. Males were predominant, mainly affecting school age, symptoms appeared in 56.6% before two years of age and 21.6% had less than one year of evolution, in 54.9% have received specialist medical treatment, only 18.3% know elementary information about the disease. As a result it improved control in 80% of cases, by means of a scheme that includes a specificity response to an integral diagnosis through the path that modify favorable risk factors in a six months period. PMID- 8210932 TI - General responses of the bone marrow to injury. AB - Hematologic responses in a toxicologic setting may be quite complex and may involve both local as well as systemic manifestations of toxicity and/or pharmacologic responses. Direct toxicity to bone marrow can lead to changes such as marrow necrosis, marrow dysplasia, and macrophage hyperplasia. Some toxic compounds can directly stimulate or suppress the development of 1 or more marrow cell lines. The marrow may also respond to injury at distant sites with increased production of various blood cell elements. Accurate interpretation of hematologic responses generally involves integration of peripheral blood data with bone marrow findings as well as toxicologic findings in other organ systems. This manuscript overviews the various marrow changes encountered in toxicologic studies and provides a perspective of how these changes are best approached from an interpretive viewpoint. PMID- 8210933 TI - Principles of hematotoxicology: laboratory assessment and interpretation of data. AB - The toxicologic evaluation of the hematopoietic system is part of most preclinical and clinical safety studies and has become routine in monitoring a variety of novel and conventional therapies in humans and animals. As with spontaneous disease, iatrogenic blood dyscrasias may be primary but are frequently secondary to other tissue toxicity. The latter tendency makes this easily accessible tissue particularly useful in monitoring for systemic toxicity, while primary hematotoxicity ranks with liver and kidney effects as important and often limiting complications. Although the principles driving the diagnostic approach to spontaneous (clinical) blood disorders generally apply to preclinical and clinical safety studies, there are important differences, particularly regarding control of variables, feasibility of testing, and interpretation of resulting data. The luxury of studying a homogenous population of subjects free of complicating disease under controlled (uniform) laboratory and environmental conditions allows changes to be defined with greater precision and sensitivity. There are generally more options regarding the assays available and frequency of monitoring. Moreover, the hierarchy of tests applied are influenced by regulatory as well as scientific or problem-driven indications. Finally, interpretation of laboratory findings is usually based on the use of subjects as their own controls (pretreatment and sequential monitoring), comparison to a control population and well-defined reference ranges specific for the population under study, and in accordance with the principles of pathology and internal medicine. PMID- 8210934 TI - Leukocyte response to toxic injury. AB - Exposure to a variety of drugs and toxins can induce hematopoietic damage. These agents exert their effects through several distinct mechanisms including destruction or suppression of hematopoietic stem cells, cytotoxic destruction of rapidly proliferating precursor cells, immune-mediated hematotoxicity, altered hematopoietic microenvironment, genetic mutation, and microvascular injury. Some toxins consistently produce suppression of granulopoiesis in a dose-dependent manner, whereas others produce idiosyncratic reactions. Although all types of injury tend to result in granulocytopenia, the time course of the changes varies with the type of injury. With acute destruction of the proliferative pool of granulocytes, neutropenia develops within 7 days and recovery occurs within days after discontinuing treatment. With stem cell injury, the onset of hematotoxicity is variable and damage is often permanent. Immune-mediated reactions may occur acutely or after months or years of treatment with a drug. Drugs or toxins that act as mutagens can induce a variety of hematopoietic disorders including aplastic anemia, myelodysplasia, and leukemia. Therefore, the time course of onset of leukopenia after drug or chemical exposure and the rapidity of hematopoietic recovery give clues to the mechanism by which granulopoiesis is suppressed. PMID- 8210935 TI - Evaluation of the influence of potential toxins on neutrophil function. AB - Neutrophils undergo a complex series of events when functioning to control bacterial, viral, and fungal infections. Any factor that interferes with neutrophil production or suppresses neutrophil function will rapidly make the animal more susceptible to infectious diseases. In vitro assays are used to detect and characterize defects in neutrophil function that may be induced by exposure to potential toxins. This paper focuses on important considerations in designing experiments for the evaluation of neutrophil function and interpretation of data. PMID- 8210936 TI - Cytokine-induced changes in the leukon. AB - Cytokines are regulatory peptides, produced by virtually every nucleated cell type in the body, that have pleiotropic effects on hematopoietic, lymphoid, and other cell types. Cytokines usually act locally as autocrine or paracrine cellular signals intended to maintain local homeostasis but in disease states can spill over into the circulation to initiate systemic reactions. The systemic administration of high doses of recombinant cytokines is associated with a multitude of pharmacologic and toxicologic effects, frequently involving the hemolymphopoietic system. These effects may represent direct or indirect pharmacologic or hyperpharmacologic activity or may represent toxicity. The objective of this review is to present the general types of hemolymphopoietic changes associated with cytokine administration to animals and to provide examples of cytokine-induced effects on the hemolymphopoietic system. PMID- 8210937 TI - Assessment of hemolytic and hemorrhagic anemias in preclinical safety assessment studies. AB - The general characteristics of anemia and the distinguishing features of hemolytic, hemorrhagic, hypoproliferative, maturation abnormality, and iron deficiency anemias are described. Hemolytic anemias are differentiated initially from hemorrhagic anemias by excluding hemorrhage on clinical, necropsy, or histologic examination. Next, they are distinguished from the remaining types of anemia on the basis of higher reticulocyte counts or, in some instances, by the very rapid rate of decline of the PCV. Hemolytic anemias are distinguished from each other on the basis of incidence and the presence or absence of a dose response (idiosyncratic vs toxic) and by the cause of hemolysis (oxidative, nonoxidative, or immune-mediated). Hemorrhagic anemias are subclassified on the basis of single- and multiple-site hemorrhage. The causes of multiple-site hemorrhage (hemostasis dysfunction) are established by first- and second-line tests, the type of bleeding, clinical data, and the information gained from an evaluation of the structure, activity, and metabolism of the compound. PMID- 8210938 TI - A review of myelofibrosis in dogs. AB - Myelofibrosis is a proliferative response of the bone marrow fibroblasts. Myelofibrosis can be classified as primary or secondary depending on the underlying etiology. Primary myelofibrosis is a myeloproliferative disorder in humans in which there is a clonal proliferation of a pluripotent stem cell. Hemopathology includes finding nucleated red blood cells and immature granulocytes in the circulation, extramedullary hematopoiesis, and myelofibrosis. The proliferation of the bone marrow fibroblasts is not clonal in origin. To the best of this author's knowledge, this type of myelofibrosis has not been reported to occur naturally in the dog. Secondary myelofibrosis has been reported in the dog associated with neoplastic conditions, irradiation, congenital hemolytic anemias, and a variety of unknown etiologies. It has been shown in some cases of myelofibrosis that there is often concurrent bone marrow necrosis. Bone marrow necrosis has been documented in dogs with Ehrlichiosis and septicemia, and associated with drug treatment, including estrogens and cephalosporins. It is though that this necrosis is due to the destruction of the bone marrow microvasculature and/or hematopoietic elements. Release of growth factors by inflammatory cells may lead to the subsequent fibroblast proliferation. Several cases of secondary myelofibrosis in female laboratory beagles have been recently observed. These dogs present with a severe nonregenerative anemia and often a mild neutropenia with varying degrees of myelofibrosis in the bone marrow. Some animals have had concurrent bone marrow necrosis. At this time, the exact etiology is unknown. PMID- 8210939 TI - An overview of hemostasis. AB - Hemostasis is a remarkable and a remarkably complex mechanism. It can maintain blood in a fluid state intravascularly but very quickly changes blood to a jellylike mass upon disruption of the vasculature. This review will give a synopsis of the 3 phases of hemostasis: platelet, vascular, and coagulation. Fibrinolysis and control mechanisms of hemostasis will also be covered. In addition, brief descriptions of the clinical and laboratory evaluation of patients and the diagnosis of bleeding disorders will be presented. PMID- 8210940 TI - Interruption of thrombosis and hemostasis by anti-platelet agents. AB - Blood platelets play a fundamental role in hemostasis and thrombosis. The physiological role of platelets is to preserve the integrity of the cardiovascular system such that upon injury platelets are activated and serve to interrupt a potentially deleterious situation (i.e., hemorrhage). However, platelets are also involved in the pathophysiology of thrombosis in which the normal repair process is grossly exacerbated, resulting in interruption of blood flow to vital tissues. Thus, a critical balance exists between the normal function of blood platelets to preserve tissue function and a pathophysiological function in which tissue is damaged due to thrombosis and subsequent ischemia. Numerous anti-platelet agents have been developed in an attempt to interrupt the thrombotic process without severely compromising the hemostatic state of patients. This article will be devoted to a discussion of a commonly utilized anti-thrombotic agent, aspirin, as well as a class of newer, possibly more effective anti-thrombotic agents referred to collectively as fibrinogen receptor antagonists. PMID- 8210941 TI - The search for the ideal thrombolytic agent: maximize the benefit and minimize the risk. AB - Streptokinase, acylated plasminogen streptokinase complex, and tissue-type plasminogen activator (tPA) are widely used for the treatment of acute myocardial infarction. These thrombolytic agents restore blood flow in occluded coronary arteries, salvage myocardial function, and decrease mortality. The success of thrombolytic therapy depends on the prompt and stable recanalization of the occluded blood vessel. Hemorrhagic events undermine the safety of fibrinolytic agents. Most bleeding complications occur at vascular puncture sites and can be avoided by limiting invasive procedures; however, an increased incidence of devastating intracranial bleeds is also encountered. The cause of thrombolytic induced intracranial hemorrhage is unknown but may be due to lysis of protective hemostatic plugs. Another potential contributor to bleeding is activation of circulating plasminogen by the exogenous plasminogen activator to yield fluid phase plasmin. Plasmin is a promiscuous proteinase that degrades many proteins that play pivotal roles in hemostasis and the integrity of the microvasculature. Tissue-type plasminogen activator activity is depressed in the absence of fibrin; hence, its use as a thrombolytic agent was anticipated to avoid the untoward consequences of plasminemia. However, the administration of pharmacologic doses of tPA can result in the activation of appreciable quantities of circulating plasminogen. In contrast to currently available thrombolytic agents, the activity of the vampire bat salivary plasminogen activator (BatPA) displays a strict requirement for the presence of fibrin. Assessment of BatPA using animal models of arterial thrombosis has demonstrated efficacy but without activation of systemic plasminogen. The avoidance of plasminemia when using BatPA as a fibrinolytic agent may circumvent bleeding complications that can compromise the safety of thrombolytic therapy. PMID- 8210942 TI - Immunohistochemistry and morphology of reactive lesions in lymph nodes and spleen from rats and mice. AB - The use of immunohistochemistry with anatomical and systematized classifications of nonneoplastic lesions in hematopoietic pathology of lymph nodes and spleens from rats and mice is described. Polyclonal antisera and monoclonal antibodies to leukocyte and other antigens can be used with frozen or fixed tissue sections to identify changes in cell populations in these tissues in response to tissue injury and aging. A classification for reactive lesions of lymph nodes and spleen is proposed that can be utilized for computerized pathology and toxicology data systems. These classifications are based on a systematized anatomic distribution of the lesions with the aid of immunohistochemistry. The association of some lesions with early leukemia or lymphoma of rats and mice is also discussed. PMID- 8210943 TI - The morphology, immunohistochemistry, and incidence of hematopoietic neoplasms in mice and rats. AB - Hematopoietic neoplasms in the rodent may be classified into lymphoid or nonlymphoid neoplasms. Lymphoid neoplasms include the following morphologic types: follicular center cell, lymphoblast (lymphocytic), immunoblast, plasma cell, and large granular lymphocyte (LGL). Nonlymphoid hematopoietic neoplasms include histiocytic sarcoma, granulocytic leukemia, erythroid leukemia, and mast cell tumors. Most types of hematopoietic neoplasms, exclusive of LGL lymphoma (leukemia), are more common in mice than in rats. Specific strains of mice have a hematopoietic tumor incidence of more than 50% in aged animals. Some strains of rats (i.e., Fischer-344) may have an incidence of over 50% of LGL lymphoma in aged animals. The tumor type and incidence are characteristic for each rat or mouse strain. Hematopoietic neoplasms have been better characterized immunomorphologically in mice than in rats. The specific cell type and tissue of origin for hematopoietic neoplasms may be important for safety evaluation of chemicals. Specific chemicals may induce specific types of these tumors, which may be the same or different from the spontaneous types. Lymphoid cell neoplasms should not be grouped with nonlymphoid neoplasms in determining the toxicity and carcinogenicity of test substances. PMID- 8210944 TI - Retrovirus-induced lymphoproliferation as a model for developing diagnostic criteria for malignant lymphoma in mice. AB - Several methods for evaluating lymphoproliferative lesions in mice were compared. The model systems included spontaneous lymphomas arising in CWD mice and NFS mice congenic for ecotropic murine leukemia virus (MuLV) induction loci and a series of transplants in mice with severe combined immunodeficiency disease mutation of cells derived from mice infected with LP-BM5 MuLV. Primary lymphomas and donor tissues and transplants were examined using histopathology, flow cytometry, and Southern blot analysis of DNA for rearrangements of immunoglobulin and T-cell receptor genes and for viral integrations. The use of flow cytometric analysis, to establish cell lineage and define population size, and DNA analysis, for cell lineage and clonality determination, allowed the identification of malignant lymphoproliferations. Histologic evaluation did not define clonal populations of particular lineage but did provide other indications of malignancy such as invasiveness and presence of a dominant morphologic cell type. Thus, the precision of diagnosis of mouse lymphomas can be considerably enhanced by augmenting histopathologic examination with antigenic and molecular characterizations that can define malignant populations. PMID- 8210946 TI - Cytokine technology in basic and applied research on the hematopoietic system. AB - Cytokines are polypeptide molecules important for the regulation and maintenance of immunity and hematopoiesis. Their central role in the control of a number of physiological mechanisms makes them an important area of both basic and applied biomedical research. This review presents an overview of basic and applied biology, and introduces the term cytokine technology to denote the use of cytokines as research tools for understanding the cellular and molecular regulation of hematopoiesis. A number of frontier technologies are reviewed, including fusion toxins, fusion proteins, and animal models of cytokine expression and regulation. PMID- 8210945 TI - Roles for in vitro myelotoxicity tests in preclinical drug development and clinical trial planning. AB - Myelosuppression is the dose-limiting side effect for most anti-cancer and many anti-human immunodeficiency virus agents, which can be quantitated with optimized colony-forming assays (granulocyte-macrophage, late erythroid, and megakaryocytic [for murine only] colony-forming units and early erythroid burst-forming units (BFUs)). When applied to new drug development, the assays are used for therapeutic index-based screening (e.g., less myelosuppressive analogues, structure-toxicity studies, new drug leads), interpreting efficacy data from xenotransplant models, and selecting the most accurate animal model for human hematopoietic toxicity. However, other types of assays may be required to identify the mechanism underlying myelosuppression. In clinical trial planning, in vitro colony-forming assays can be used to elucidate schedule dependency of myelotoxicity (which in turn provides clues about mechanism of action), to plan cytokine support, and to estimate dose-escalation effects. The inhibition of colony formation can be measured relative to a compound with known clinical myelotoxicity and schedule dependency to provide some idea of the toxicity expected at particular doses, and the degree of heterogeneity between individuals, during clinical trials. The predictive accuracy of the in vitro data has been proven by validation studies with alkylating agents. PMID- 8210947 TI - Tumor cell interactions with stromal elastin and type I collagen: the consequences of specific adhesion and proteolysis. AB - Elastin and collagen are abundant fibrous molecules in the stroma. Tumor cells invading the stroma are in contact with fibers of both types much of the time. Both may serve as footholds for the traction required for movement. Elastin has an additional role. Elastin peptides are known to stimulate receptor signaling and chemotaxis, which could explain the morphometric changes (membrane and organelle polarization and cell volume shrinkage) that we have reported for certain tumor cell lines invading elastic lamina. Elastin and its peptides emerge as possible invasion enhancers for some tumor cells. In ongoing work we are screening human tumors that contact elastin (e.g., breast carcinomas) to see if the presence of elastin receptors correlates with early dissemination of metastatic tumor cells. PMID- 8210948 TI - Responsiveness of murine lymphokine-activated killer activity to prostaglandin E2 at late phase of interleukin-2 induction. AB - To elucidate the inhibitory effect of prostaglandin E2 (PGE2) on the generation of recombinant interleukin-2 (IL-2)-induced lymphokine-activated killer (LAK) activity, we have examined the association between cellular 3',5'-cyclic adenosine monophosphate (cAMP) and cytolytic activity of 3-day IL-2-cultured murine LAK cells, i.e. at late phase of IL-2 induction, in the presence and absence of PGE2. The results indicate that, at the late phase of IL-2 induction, LAK cells retain their responsiveness to PGE2 inhibition, and the inhibition can be partially suppressed by additional IL-2 in proportion to the decrease in the ratios of stimulated to basal cellular cAMP levels. PMID- 8210949 TI - On the origin of pancreatic endocrine cells, proliferation and neoplastic transformation. AB - In the adult mouse, pancreatic islets contain four islet cell types: alpha, beta, delta and pancreatic polypeptide cells that synthesize glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. The early progenitor cells to the pancreatic islets are multipotential and coactivate all the islet-specific genes from the time they first appear. As development proceeds, expression of islet-specific hormones becomes restricted to the pattern of expression characteristic of mature islet cells. The phenotype of mature islet cells, however, is not stable since different environmental stimuli can induce the reappearance of embryonal traits in mature beta cells. PMID- 8210950 TI - Peptide hormone processing in tumours: biogenetic and diagnostic implications. AB - Insight into the biogenesis of peptide hormones has grown explosively by elucidation of gene, mRNA and prohormone structures. In addition, information about prohormone processing enzymes is rapidly accumulating. Prohormones vary in size and organization from poly- to monoprotein structures. According to their structural organization and sequence homology, hormones are grouped in families. Prohormones are processed to bioactive peptides by multiple modifications during the transport from the endoplasmic reticulum to secretory granules. The modifications comprise different proteolytic cleavages and amino acid derivatizations. By constitutive secretion, the processing is less pronounced. The same prohormone may be expressed in several cell types that process the precursor in different ways. Awareness of cell-specific processing patterns is important for understanding the tumour synthesis of peptides and for appropriate diagnosis of peptide-producing tumours. These tumours comprise not only well known neuroendocrine neoplasias. An increasing number of common carcinomas also expresses peptide hormone genes. However, the translation and post-translational processing in tumours are generally attenuated. Consequently, the expression is often functionally and clinically silent. A new diagnostic tool, processing independent analysis (PIA), seems promising in quantitation of hormone gene expression at peptide level irrespective of the degree of processing. Studies of progastrin expression and processing in tumours illustrate the diagnostic superiority of PIA. PMID- 8210951 TI - Factors controlling pancreatic islet neogenesis. AB - We have established a model in which cellophane wrapping induces reiteration of the normal ontogeny of beta-cell differentiation from ductal tissue. The secretion of insulin is physiologic and coordinated to the needs of the animal. Streptozotocin-induced diabetes in hamsters can be 'cured' at least half the time. There appears to be activation of growth factor(s) within the pancreas acting in an autocrine, paracrine or juxtacrine manner to induce ductal cell proliferation and differentiation into functioning beta-cells. Given the results of our studies to date, it does not seem premature to envisage new approaches to the treatment of diabetes mellitus. Identification of the factor(s) which regulates islet cell proliferation and differentiation in our model may permit proto-undifferentiated cells and islets to be grown in culture. This concept could be extended to induce endocrine cell differentiation in vitro as well. Furthermore, islet cell growth factors could be used to provide 'trophic support' to islet transplants as a means of maintaining graft viability. There may also be greater scope for gene therapy when the growth factor(s) has been isolated, purified, sequenced and cloned. PMID- 8210952 TI - [Benign tumors and pseudo-tumors of the jaws]. PMID- 8210953 TI - An audiological survey of officers at an infantry regiment. AB - We carried out an audiological survey of 204 officers at an infantry regiment in southern Sweden. The officers were exposed to impulse noise from firearms with peak levels up to 185 dB (SPL). The audiological measurement results were summarized in four age-groups, all of which showed significant hearing loss compared to ISO 1999 (1990) database A of a non-noise-exposed male population. Even officers who claimed regular use of hearing protectors during their entire military career showed these significant hearing losses. In the survey we also studied the association of the hearing thresholds with subjective exposure to heavy detonations and the annoyance of tinnitus. We found a significant relation between exposure to heavy detonations and tinnitus. PMID- 8210954 TI - The effect of hearing loss on ABR interpretation: use of a correction factor. AB - Patients suspected of retrocochlear disorders often have abnormal ABRs in the presence of high-frequency hearing loss, making clinical decisions difficult. In a retrospective study of the ABR test results of 1539 patients, the false positive and false-negative rates for ABR are presented as a function of hearing loss at 4000 Hz, both before and after using Selters and Brackmann's correction factor for hearing loss. For patients with more than 50 db HL at 4000 Hz the false-positive and false-negative rates, uncorrected for hearing loss, were 25.0% and 2.9% respectively, and when the correction factor was used were 12.5% and 5.8%. When hearing loss at 4000 Hz was over 90 dB the ABR was abnormal in 75% of nontumor patients. Conclusions are that a correction factor for hearing loss is helpful with reservations, and that ABR is not a useful test when 4000 Hz hearing loss is greater than 90 dB HL and 2000 Hz is greater than 75 dB HL. PMID- 8210955 TI - Clinical significance of probe-tone frequency ratio on distortion product otoacoustic emissions. AB - Parametric variations in the ratio of primary-tone frequencies were explored to optimize the amplitude of the 2f1-f2 distortion product otoacoustic emission for clinical purposes. Ten ears from 5 normally hearing human subjects were examined with primary tones geometrically centred around the standard audiometric frequencies of 0.5, 1, 1.5, 2, 3, 4, 6 and 8 kHz. The distortion product at the frequency 2f1-f2 (f1 < f2) was measured at six probe tone frequency ratios (f2:f1) varying between 1.15 and 1.40 using equal level primaries of 75 dB SPL. The results showed that a single f2:f1 ratio between 1.20 and 1.25 provides a reasonable value for clinical use in that it optimizes the magnitude of the distortion product at 2f1-f2, provides for sufficient resolution in the test frequency range, and is applicable to the standard clinical test frequencies. PMID- 8210956 TI - Computer-aided hearing threshold determination from cortical auditory evoked potentials. AB - The determination of the hearing threshold from cortical electric responses is usually based on the visual inspection of the recordings by an experienced evaluator. At least two factors are responsible for the limited reliability of such a procedure: first, visual inspection yields the response threshold and not the hearing threshold; and second, the result of a visual evaluation depends on subjective appraisal, which may be influenced by irrational factors. An approach of computer-aided evaluation is presented which simulates the visual inspection in that several typical features of the curves are judged numerically. The result of the classification is a single parameter, Q, whose value increases with better (subjective) perceptibility of the evoked potentials. A statistical analysis explores the relationship between the value of Q and the psychophysical hearing threshold. The results show that a prediction of hearing threshold with an accuracy of +/- 10 dB is possible. PMID- 8210957 TI - Vibrotactile support: initial effects on visual speech perception. AB - The study investigated the initial effects of the implementation of vibrotactile support on the individual's speech perception ability. Thirty-two subjects participated in the study; 16 with an acquired deafness and 16 with normal hearing. At a general level, the results indicated no immediate and direct improvement as a function of the implementation across all speech perception tests. However, when the subjects were divided into Skilled and Less Skilled groups, based on their performance in the visual condition of each test, it was found that the performance of the Skilled subjects deteriorated while that of the Less Skilled subjects improved when tactile information was provided in two conditions (word-discrimination and word-decoding conditions). It was concluded that tactile information interferes with Skilled subjects' automaticity of these functions. Furthermore, intercorrelations between discrimination and decoding tasks suggest that there are similarities between visually and tactilely supported speechreading in how they relate to sentence-based speechreading. Clinical implications of the results were discussed. PMID- 8210958 TI - Acoustic resonators in the coupler and in the ear. AB - The acoustic effect of four resonators on the output of a single hearing aid was measured on ten subjects. The purpose was to compare the effect of each of the resonators in a 2 cc (2 cm3) coupler and in real ears. Two of the resonators were special earhook resonators and the other two were contained in the earmolds. The output of the hearing aid with a standard earhook-earmold configuration was compared to the output of the hearing aid through each of four earmold-earhook configurations. One resonator was present in each of the nonstandard systems. Each of the four comparisons was made in (1) the real ears using a probe microphone in a sound-treated test booth and (2) in the coupler with the hearing aid placed in a sound-treated test box. Predictable, systematic differences were found between the 2 cc coupler measurements and the real-ear measurements. Therefore, a reliable transfer function for each resonator can be expected when 2 cc coupler specifications are used to fit resonators for specific hearing losses. PMID- 8210959 TI - Allergy caused by light-cured ear-moulds. AB - This investigation was conducted after the occurrence of allergic contact dermatitis in three laboratory technicians all engaged in the production of UV light-cured acrylate ear-moulds. Ninety patients fitted with such moulds claimed discomfort to the same extent as patients with traditionally made acryl moulds. Of thirteen patients seen for clinical examination, seven were tested for allergy in the same way as the technicians and four were found to be sensitized to monomere metacrylates in the wax. The handling of the base materials in the laboratory as well as the UV-light-curing procedure needs further investigation. PMID- 8210960 TI - Microcomputer with a sound card. Low-cost flexibility for audiometry. AB - An ordinary Personal Computer equipped with a sound card for entertainment electronics can significantly improve the flexibility of speech and pediatric audiometry. New programming tools have made it possible for the layman to construct his own user-interface. PMID- 8210961 TI - Effects of contralateral acoustic stimulation on otoacoustic emissions following vestibular neurectomy. AB - This study demonstrates that, following unilateral vestibular neurectomy, the inhibitory effect of contralateral acoustic stimulation on evoked otoacoustic emissions is absent. The patient acts as her own control in that the unoperated side shows normal suppression of otoacoustic emission amplitude with contralateral acoustic stimulation. The lack of interaural suppression of otoacoustic emissions on the sectioned side, in the presence of normal acoustic reflex threshold levels, provides evidence that observed phenomena are not merely a function of middle ear reflex activity. It is concluded that the lack of inhibition in the operated ear is due to the sectioning of the olivocochlear bundle within the inferior vestibular nerve, removing the efferent control of the receptor cells. Otoacoustic emissions recorded during contralateral acoustic stimulation may thus provide a rapid, non-invasive means of investigating the functional of the efferent auditory system. PMID- 8210962 TI - Binaural interaction in the auditory brainstem response. Multichannel recordings. AB - Binaural interaction (BI) waveforms were derived from multichannel recordings of auditory-evoked brainstem responses obtained at moderate and high intensity levels. The component latencies of all the BI responses derived from the contralateral channel were significantly prolonged compared with those derived from ipsilateral and non-cephalic channels. These channel differences were identified only at the moderate intensity level, indicating that BI cannot be isolated from the effects of stimulus interaction at higher intensities. The amplitudes were not significantly different across channels or intensities, indicating that ipsilateral, contralateral or non-cephalic recordings can be used to study BI. However, identification of channel differences on simultaneous multi channel recordings may provide an index of true neural interaction. PMID- 8210963 TI - Electromagnetic stimulation of the auditory system: effects and side-effects. AB - Extracranial electromagnetic stimulation (EMS) is a recently developed clinical technique which may be used in place of conventional transcutaneous electrical stimulation to activate the central and peripheral nervous systems. This technique is widely used in neurology and otolaryngology for non-invasive stimulation of the brain and facial nerve. EMS uses electromagnetic field pulses which pass unimpeded through the cranium and soft tissues to activate excitable membranes of volume conductors. In this series of studies, the effects and side effects of electromagnetic stimulation on the auditory system of humans and experimental animals were investigated. In the first study, 18 profoundly hard-of hearing and deaf patients who were candidates for cochlear implants were examined by non-invasive EMS in an effort to determine whether EMS could stimulate residual neurons in the cochlea, 8th nerve proper, or higher auditory brain centers, and evoke auditory sensations. The patients were stimulated with a magnetic coil positioned at the (1) auricle, (2) mastoid process, and (3) the temporal lobe area. EMS elicited auditory sensations in 26 ears (of 14 patients/subjects). The lowest threshold of auditory sensation (TAS) at each stimulus position was found to be at the 20% EMS level, with a range of 20-50% of the maximum level (2.0 Tesla), and with equal sensitivity in each coil position. There was no correlation between the EMS/TAS and the immediate postoperative psychoacoustic tests in ten patients receiving cochlear implants. A prominent side effect of EMS was found to be the high intensity, high frequency impulse noise generated by the coil which causes severe cochlear damage and permanent sensorineural hearing loss in experimental animals. Measurements of the sound pressure level (SPL) of the magnetic coil acoustic artifact (MCAA) at the tympanic membrane of the rabbit ear showed levels of up to 160 dB for maximum EMS. Measurements of the spectral content and SPL of the MCAA in the ear canal of life size models of the human cranium with the stimulating coil placed at standard clinical positions indicated that the major acoustic energy of the pulse is concentrated in the 2-5 kHz range, and that the SPL of the pulse at some positions may place persons at risk for hearing loss. Studies on computer simulated impulse noises showed that the peak sound pressure rather than the rise time (in the range 0.1-1.0 ms) determined the permanent threshold shift (PTS). The MCAA was more harmful than a 128 dB SPL continuous noise with 100 times more energy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8210964 TI - Magnetic resonance imaging and spectroscopy of the human heart. AB - Magnetic resonance imaging and spectroscopy have a great potential both for clinical cardiac diagnostics and for research in cardiac physiology, metabolism and disease. At the present time, cardiac MRI already is the method of choice in several clinical conditions, especially in imaging central vasculature and intra- and paracardiac masses. With the recent development of contrast agents and ability to measure both flow velocities and flow volume, the cardiac MRI is likely to have a profound role in evaluating coronary arterial disease as well as valvular heart disease. The limitations due to long imaging times of cardiac MRI studies are likely to be overcome with the development of ultrafast imaging techniques in the near future. On the other hand, cardiac MRS is still a research tool, which needs technical improvements before it can be widely utilized in clinical work. However, attempts to this aim are highly justified, when the possibility that MRS will provide metabolic information of the heart is considered and bearing in mind, that MR-magnets with sufficient field strength for MRS are increasingly in use in most modern hospitals. The role of magnetic resonance imaging (MRI) and spectroscopy (MRS) in the evaluation of heart diseases is still evolving. Some clear indications for clinical use of cardiac MRI have already become apparent, whereas cardiac MRS is still confined to research applications. The current paper consists of a review of the role of MRI for cardiovascular diagnosis together with a review of the currents status of cardiac MRS. PMID- 8210965 TI - The diagnostic and prognostic value of serum bone Gla protein (osteocalcin) in patients with recurrent breast cancer. AB - Serum bone Gla protein (S-BGP), a marker of bone metabolism, was measured in 60 patients included in a staging programme for recurrent breast cancer. Other diagnostic procedures comprised S-alkaline phosphatase (S-AP), bone scan (B scan), bilateral iliac crest bone marrow biopsies, and radiological bone survey. The sites of recurrence were bone (61%), bone marrow (46%), soft tissue (52%), lung (13%), pleura (11%), liver (4%), and brain (2%). Radiology and bone biopsy served as key diagnoses as to the presence or absence of bone metastases. The diagnostic efficiency of B-scan and S-AP was greater than that of S-BGP, and the result of BGP measurement was associated with neither extent nor number of bone metastases. However, the BGP values were significantly lower in patients who had visceral metastases, and the median duration of survival after recurrence was 13 months for patients with low S-BGP levels (= < 2.0 nmol l-1), compared to 18 months for patients with medium S-BGP values (2.0-2.9 nmol l-1), and 25 months for patients with high values (> 3.0 nmol l-1) (p = 0.19). Analyses of the simultaneous effect of univariate prognostic factors were performed using the Cox proportional hazards model. S-alkaline phosphatase (S-AP) and S-BGP were the only significant, independent prognostic factors. PMID- 8210966 TI - Oxygen radicals stimulate thromboxane and prostacyclin synthesis and induce vasoconstriction in pig lungs. AB - Reactive oxygen species have earlier been shown to induce vasoactive changes. In the present investigation we hypothesized that active oxygen intermediates would stimulate arachidonic acid metabolism and thereby influence the pulmonary circulation. Four groups of 8-week old pigs were studied after infusion of an oxygen radical generator. Haemodynamic changes were recorded, and thromboxane (TX)B2 (the stable metabolite of TXA2) and 6-keto-prostaglandin (PG)F1 alpha (the stable metabolite of prostacyclin, PGI2) measured by a radioimmunoassay technique after infusion of xanthine oxidase (XO) alone or in combination with pharmacological inhibitors. In the XO group pulmonary vascular resistance increased rapidly compared to baseline levels. Maximum resistance increase was 118.4 +/- 27.5%, 25 min after the XO infusion (p < 0.05 compared to baseline). The vasoconstriction was significantly attenuated after pretreatment with the cyclo-oxygenase inhibitor indomethacin. In this group the pulmonary resistance increase was 21.2 +/- 24.3% at 25 min (p < 0.01 vs. XO group). In a group given allopurinol (xanthine oxidase inhibitor), the resistance increased by 44.3 +/- 28.8% (p < 0.02 vs. XO group), and during catalase infusion (hydrogen peroxide scavenger), the increase was 52.9 +/- 24.2% (p < 0.01 vs. XO group). Along with the pulmonary vascular pressure augmentation, we measured 1.9 fold TXB2 and 2.2 fold 6-keto-PGF1 alpha concentration increases in the XO group. However, both TXB2 and 6-keto-PGF1 alpha formation was significantly inhibited by indomethacin (p < 0.01 respectively vs. XO group), allopurinol (p < 0.01 and p < 0.05 respectively vs. XO group) and catalase (p < 0.01 and p < 0.02 respectively vs. XO group).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210967 TI - Effectiveness of low-dose lovastatin combined with low-dose colestipol in moderate to severe primary hypercholesterolaemia. AB - The effect of the combination of low-dose lovastatin and low-dose colestipol was studied among 57 subjects with moderate to severe primary hypercholesterolaemia (total cholesterol > or = 7.0 mmol l-1). Following an 8-week dietary phase, participants were randomized to treatment with 20 mg of lovastatin combined with 5 g or with 10 g of colestipol, or to matching placebo. Baseline total cholesterol was 7.7 +/- 0.9 mmol l-1 after dietary stabilization. Total cholesterol levels were reduced to 5.6 +/- 0.7 mmol l-1 and 5.8 +/- 0.7 mmol l-1 after 4 and 8 weeks of treatment in the lovastatin 5 g-1 colestipol group, and 74% of the subjects achieved the goal of low density lipoprotein (LDL) cholesterol levels of > or = 4.0 mmol l-1. Among the lovastatin 10 g-1 colestipol group, total cholesterol was reduced to 5.4 +/- 0.5 mmol l-1 and 5.5 +/- 0.9 mmol l-1 following 4 and 8 weeks, and 80% of subjects achieved the LDL cholesterol goal. No change was seen in the placebo group. Thus, low-dose combination therapy with lovastatin and colestipol, in conjunction with dietary treatment, is effective in moderate to severe primary hypercholesterolaemia, and is well tolerated. PMID- 8210968 TI - Homocysteine in frozen plasma samples. A short cut to establish hyperhomocysteinaemia as a risk factor for arteriosclerosis? AB - Findings in several retrospective studies have supported the hypothesis that hyperhomocysteinaemia may be an independent risk factor for premature arteriosclerotic disease. This prompted us to investigate whether frozen plasma samples could be used to study the question prospectively. Total plasma homocysteine concentrations in 6-16-year-old (10.9 +/- 2.5, mean +/- SD) frozen ( 20 degrees C) and fresh samples from the same 76 men were 11.6 +/- 4.9 and 14.1 +/- 4.3 mumol l-1 respectively, the values being significantly correlated (r = 0.58, p < 0.001). The difference was not correlated to storage time. After the first sampling, 13 subjects had survived a stroke, 16 a myocardial infarction, and 51 were still healthy, being used as matched controls. In stroke patients, values from old and fresh samples were 14.2 +/- 5.5 and 16.4 +/- 4.8 mumol l-1, respectively, and tended to be higher (p = 0.06) than in matched controls whose respective values were 11.4 +/- 2.8 and 13.8 +/- 3.8 mumol l-1 (n = 22). No such differences were seen between patients with myocardial infarction and their matched controls. We conclude that total plasma homocysteine can be measured in up to 10-year-old frozen plasma samples, indicating that such samples can be used for prospective studies on the relationship between plasma homocysteine and vascular disease. PMID- 8210969 TI - Cyclosporine A monitoring in patients with renal, cardiac, and liver transplants: a comparison between fluorescence polarization immunoassay and two different RIA methods. AB - In the present study a new method for selectively determining parent cyclosporine (CsA) in whole blood, a fluorescence polarization immunoassay (FPIA; TDx Abbott), was compared with a RIA method (Sandimmun, Sandoz Ltd, Basle, Switzerland). A total of 974 samples were collected during the first 3 post-operative months from 63 renal, cardiac, and liver transplant recipients. The CsA concentrations measured with FPIA ranged from 14% to 19% above RIA (specific) in the middle ranges. Regression equations in renal transplants: FPIA = 1.001 x RIA + 28; in heart transplants: FPIA = 1.08 x RIA + 27 and in liver transplants: FPIA = 1.13 x RIA + 13. Considering the improved precision of the new method (inter-assay CV with FPIA: 3.8-9.5%; with RIA: 18.6%), the slightly lower specificity will usually be of minor importance in the therapeutic range for whole blood CsA concentrations following organ transplantations. The FPIA measurements which deviated most from the regression line compared with RIA-specific CsA values, tended to coincide with high CsA concentrations or rather extreme RIA specific to RIA non-specific ratios. In addition to analytical imprecision with the RIA specific method, lower specificity of the FPIA vs. some of the metabolites may explain these deviations. The majority of these observations occurred as isolated episodes with normal relationship between RIA specific and FPIA on preceding and following days. Accordingly large dosage adjustments should await verification in repeated samples. Following these precautions the FPIA method may prove useful and safe in the monitoring of cyclosporine treatment. PMID- 8210970 TI - Unchanged noradrenaline reactivity and blood pressure after corrective surgery in primary hyperparathyroidism. AB - In order to evaluate the role of the hyperparathyroid state for blood pressure and volume homeostasis, eight patients with primary hyperparathyroidism were studied before and after corrective surgery. Neither noradrenaline induced blood pressure changes nor basal blood pressure were affected by the operation, and the values were the same as in an age- and sex-matched control group. Noradrenaline infusion induced an increase in PTH(1-84) values before (72-86 ng l-1, medians, p < 0.02), in contrast to a decrease after (28 to 19 ng l-1, p < 0.05) operation for primary hyperparathyroidism. Basal plasma atrial natriuretic peptide was lower before than after removal of adenomata (3.2 vs. 4.8 pmol l-1, medians, p < 0.02). Cyclic 3'-5'-guanosine monophosphate was not significantly changed (4.7 vs. 5.5 nmol l-1). Aldosterone was higher before than after surgery (139 vs. 71 pmol l-1, p < 0.02), whereas angiotensin II was unaltered (20 vs. 9 pmol l-1). Arginine vasopressin was higher before than after the operation (0.9 vs. 0.7 pmol l-1, p < 0.05), but urinary excretion of prostaglandin E2 was unchanged. In conclusion primary hyperparathyroidism was not associated with changes in noradrenaline reactivity or basal blood pressure despite derangements of hormones adjusting sodium and water homeostasis. It is suggested that the hormonal changes may be secondary to a relative volume depletion. PMID- 8210971 TI - Oligoclonal IgG in cerebrospinal fluid detected by isoelectric focusing using PhastSystem. AB - Identification of oligoclonal immunoglobulin G (IgG) in cerebrospinal fluid (CSF) is one of the major laboratory signs in multiple sclerosis (MS). Oligoclonal IgG can also be seen in other immunostimulating central nervous system diseases, e.g. meningitis caused by Borrelia spirochetes. A convenient isoelectric focusing (IEF) method combined with polyethyleneglycol-enhanced (PEG) immunofixation and silverstaining using PhastSystem for detection of oligoclonal IgG bands in serum and unconcentrated spinal fluid was developed. Serum and cerebrospinal fluid samples earlier investigated using agarose IEF combined with immunoblotting and avidin-biotin amplified double-antibody peroxidase staining (= A-IEF) were blindly re-analysed using PhastGel IEF 3-9 modified with addition of Pharmalyte 8 10.5 followed by immunofixation and silver staining (= PhastIEF). PhastSystem IEF using PhastGel had the same capability to separate and visualize oligoclonal IgG bands as the conventional agarose IEF. However, PhastIEF was more convenient and less time-consuming than A-IEF. PhastIEF combined with immunofixation and silver staining using application of standardized amounts of IgG for both the serum and CSF samples (40-60 ng IgG/lane is fast, well-standardized and reproducible. The method is sensitive and uses only a minute volume of unconcentrated cerebrospinal fluid for the investigation of CSF IgG pattern. PMID- 8210972 TI - Studies on triglyceride metabolism: phosphatidate phosphohydrolase from guinea pig harderian gland. AB - The guinea pig Harderian gland, located in the orbit, is characterized by a high production of lipids. However, little is known about the regulation of the metabolic pathways involved. In the present paper the properties of guinea pig Harderian gland phosphatidate phosphohydrolase, a key enzyme in triglyceride biosynthesis, was investigated. The enzyme was present both in the cytosolic and the microsomal fraction from the gland. Cytosolic phosphatidate phosphohydrolase was purified by hydroxylapatite chromatography. The enzyme was dependent on magnesium ions and inhibited in the presence of fluoride. The dependence on the substrate phosphatidate was investigated and the apparent Km for phosphatidate was about 0.6 mM. Phosphatidate phosphohydrolase activity was influenced by different phospholipids. As is the case for the rat liver enzyme, phosphatidylethanolamine was found to stimulate the enzyme activity. The results indicate that Harderian gland phosphatidate phosphohydrolase has similar properties as the corresponding enzyme from rat liver, suggesting that it may be of regulatory importance. PMID- 8210974 TI - Estimation of blood-glucose variability in patients with insulin-dependent diabetes mellitus. AB - The aim of the study described here was to evaluate the standard deviation (SD) as a measure of blood-glucose variability in IDDM patients under 'normal life' conditions. One hundred IDDM patients performed self-monitoring of blood glucose (SMBG) five times every 2 days for 4 weeks. From these records the following measurements were calculated for each patient: the standard deviation of all blood-glucose values (SDBG), the M-value, the percentage of values < 3 and > 15 mmol l-1 (PE), and the mean, absolute difference of consecutive blood-glucose values (MAD), a novel measure of blood-glucose variability, also taking into consideration the succession of the values. Before the study the patients as well as their physicians were asked to estimate the blood-glucose stability of the patient, using a five-category scale of statements. The patients recorded an average of 64 (range: 32-70) SMBG values. The SDBG was normally distributed with a mean of 3.9 +/- 1.0 mmol l-1. There was a highly significant correlation between the SDBG and the other measures of blood-glucose variability (p = 0.0001, r > 0.8). It appeared that the variation of the SMBG values recorded before dinner contributed to the total glucose variability to a great extent. There was a poor agreement between the subjective estimations of the blood-glucose stability made by the patients and the physicians and the objective measures of the blood-glucose variability. It is concluded that the SD provides an accurate and easily available estimate of blood-glucose variability in IDDM patients practising home blood-glucose monitoring. PMID- 8210973 TI - Erythrocyte deformability, endothelin levels, and renal function in cyclosporin treated renal transplant recipients: effects of intervention with fish oil and corn oil. AB - Twenty nine stable renal transplant recipients, 10 receiving cyclosporin, 10 cyclosporin-prednisolone and nine azathioprine-prednisolone were supplemented in a double blind randomization cross-over study with fish oil and corn oil for a period of 4 months each. Erythrocyte deformability was reduced in the cyclosporin treated patients and returned to normal values after supplementation of either oil. The oil supplementation resulted in an increased polyunsaturated fatty acid content in the plasma phospholipids. An increased erythrocyte membrane polyunsaturated fatty acid content might correct the lower erythrocyte deformability in cyclosporin treated patients. Therefore, it is probable that these changes are membrane-related. The oil supplementation had no effect on glomerular filtration rate, effective renal plasma flow, filtration fraction or blood pressure, which does not exclude effects of the cyclosporin-induced rigidified erythrocytes in the acute phase of renal transplantation. Decreased erythrocyte deformability could play a role in the cyclosporin-induced deterioration of renal haemodynamics. This may enhance the effects of endothelin, as these patients also had elevated endothelin levels. PMID- 8210975 TI - Retinol and retinyl esters in rabbit bone marrow and blood leukocytes. AB - Due to the well documented effects of retinoids on growth and differentiation of some leukaemic cells in vivo and in vitro, we measured the amount of retinol and retinyl esters in bone marrow, blood leukocytes, and liver in rabbits fed large doses of retinyl palmitate. Both Chinchilla rabbits and Watanabe Heritable Hyperlipidaemic rabbits which lack functional low density lipoprotein receptors, were fed 26 mumoles (25.000 IU) of retinyl palmitate daily for 8 weeks. The animals stored retinoids in large amounts in the liver, whereas only minor amounts were stored in bone marrow. More than 97% of the retinoids in the liver was esterified, while most of the retinoids in bone marrow were unesterified. We also studied the post-prandial increase in chylomicron associated retinyl esters in rabbit leukocytes in vivo. After administering an oral load of 26 mumoles retinyl palmitate, retinoids increased four-fold in blood leukocytes after 5 h. There was almost no difference in retinoid uptake in leukocytes in Watanabe Heritable Hyperlipidaemic rabbits compared to normal rabbits, suggesting that chylomicron remnant retinyl esters are taken up in peripheral blood leukocytes independently of the low density lipoprotein receptor. In conclusion, bone marrow does not store high amounts of retinoids, and retinyl ester transport and storage appear normal in absence of functional low density lipoprotein receptors. PMID- 8210976 TI - Ion effects in measurement of sodium and ionized calcium in direct potentiometry. AB - In some instruments that measure sodium directly in whole blood, plasma, or serum using ion selective electrodes (direct potentiometry), the higher the ionic strength of the solution, the lower is the sodium recovery in serum, as predicted by theory. The same could be expected for ionized calcium. When measuring the recovery of serum sodium on indirect potentiometric instrument and by flame photometry, which determine concentration in prediluted samples, and on direct potentiometric instruments, we observed that two out of the three direct potentiometry instruments showed a decreased recovery of sodium, as the ionic strength was increased, while on all the other instruments the recovery was complete. No effect of increased ionic strength was noted on the ionized calcium measurements in serum on all the instruments tested. Analysing pure aqueous solutions of sodium and calcium chloride with increased ionic strength on the same instruments, the sodium recovery was always complete or positive, and the same was true for ionized calcium. We postulate some effect of ionic strength on the salt bridge of the measuring systems, which is different when analysing serum or pure aqueous solutions. PMID- 8210977 TI - Incomplete recovery of sodium determined in direct potentiometry in blood samples added with heparin salts. AB - The recent introduction on the market of apparatus for combined blood gas electrolyte and ionized calcium analyses has raised the problem of whether the same sample can be submitted to all the analyses without generating problems for some analytes. The problem is basically connected to the common use of heparin as an anti-coagulant. To elucidate the possible effect of heparin on measurements we added pooled sera to tubes containing dried heparin/sodium chloride in increasing quantity. Our data demonstrate that, for one direct potentiometric instrument, the sodium recovery is reduced by a moderately high (70-130 IU ml-1) concentration of heparin or by the concomitant addition of the sodium ion which increases the ionic strength of the sample. The effect of the increased sodium chloride was studied separately, adding pooled sera to tubes containing dried sodium chloride in increasing quantity. The sodium recovery was reduced when the ionic strength of the sample was increased. We were unable to separate the negative effects on the sodium recovery due to heparin and due to the increased ionic strength in the sample. PMID- 8210979 TI - Same-day upper and lower endoscopy in patients with occult bleeding, melena, hematochezia, and/or microcytic anemia. A retrospective study of 224 patients. AB - The purpose of this study was to evaluate the role of same-day upper and lower endoscopy in patients investigated for non-acute gastrointestinal bleeding, manifested by occult bleeding, melena, or hematochezia and/or anemia suspected to be caused by gastrointestinal bleeding. A total of 224 patients, 127 women and 97 men, were reviewed. A potential bleeding source (PBS) in the upper gastrointestinal tract could have been missed in 25% of the patients if only colonoscopy had been performed. In nearly the same proportion of patients (26%) a potential bleeding source could have been missed if only esophagogastroduodenoscopy had been performed. Nine per cent of the patients had a potential bleeding source in both locations. Forty-six per cent (19 of 41) of the patients with a PBS in colon, other than colonic cancer, had a PBS also in the upper gastrointestinal tract. The chance of finding a potential bleeding source in patients with microcytic anemia and positive Hemoccult test is threefold higher than for the patients with microcytic anemia and negative Hemoccult test and twofold higher than in patients with normal blood hemoglobin value but positive Hemoccult test. Moreover, 22% (8 of 36) of the patients with microcytic anemia and a positive Hemoccult test had colonic carcinoma. Approximately 30% of the patients with a PBS had two or more PBSs in one or more organs. Eighteen per cent of 43 patients with a history of upper gastrointestinal symptoms had a PBS in the upper gastrointestinal tract. The corresponding figure for the patients without a history of upper gastrointestinal symptoms was 29%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210978 TI - The fate of ingested 14C-urea in the urea breath test for Helicobacter pylori infection. AB - The metabolic fate of the radioactive carbon in the 14C-urea breath test for Helicobacter pylori was investigated in 18 subjects. After ingestion of labelled urea, breath was sampled for 24 h, and urine was collected for 3 days. Subjects were designated high or low expirers on the basis of their breath counts, and this agreed well with H. pylori serologic analyses. When given 185 or 37 kBq of 14C-urea, 51% (SD = 16%, n = 11) of the label was recovered from the breath of high expirers, and 7% (SD = 3%, n = 7) from the breath of low expirers. The mean combined urinary and breath recovery for high expirers was 86% (SD = 7%), and for low expirers it was 97% (SD = 3%). It is concluded that the long-term retention of 14C from ingested 14C-urea is low. The results enable a more accurate estimation to be made of radiation exposure resulting from the 14C-urea breath test. PMID- 8210980 TI - Immunologic and absorptive tests in celiac disease: can they replace intestinal biopsies? AB - The sensitivity and specificity of several immunologic and absorption tests were determined in infants with celiac disease (31 male, 39 female; median age, 2.6 years) in different phases of the disease and in a group of control subjects with chronic diarrhea of different etiologies (32 male, 28 female; median age, 1.2 years). Intestinal biopsy was performed both in the patients and in the controls as a 'gold standard' for the diagnosis. The anti-gliadin antibody (AGA) IgG values showed a sensitivity of 89% and a specificity of 47%; AGA IgA were 69% sensitive and 92% specific; anti-endomysial antibodies (EmA) were 100% sensitive and 97% specific; the xylose test was 71% sensitive and 53% specific; and the steatocrit test after a standard fatty meal was 73% sensitive and 42% specific. The authors conclude that the absorption tests cannot be used successfully in screening for celiac disease, owing to their low specificity. In contrast, EmA behavior was always in accordance with histologic findings in the various phases of celiac disease, and we would advise their use combined with AGA to obtain a sensitivity and specificity of 100%. PMID- 8210981 TI - Drug metabolism and genetic polymorphism in subjects with previous halothane hepatitis. AB - To test the hypothesis that halothane hepatitis is caused by a combination of altered drug metabolism and an immunoallergic disposition, the metabolism of antipyrine, metronidazole, sparteine, phenytoin, and racemic R- and S-mephenytoin was investigated in seven subjects with previous halothane hepatitis. The HLA tissue types and the complement C3 phenotypes were also determined. The metabolism of antipyrine and metronidazole was within normal range in all subjects, and they were all fast or extensive metabolizers of sparteine, mephenytoin, and phenytoin. HLA tissue types were unremarkable. Five of the seven subjects had complement C3 phenotypes F or FS. In the general population phenotype S is the most common, but the difference in complement C3 phenotypes is not statistically significant (p = 0.07). We conclude, although in a limited number of patients, that subjects with previous halothane hepatitis do not appear to be different from controls with regard to drug metabolism and HLA tissue type. The possibility of a higher frequency of complement C3 phenotype F and FS needs further investigation. PMID- 8210982 TI - Quality of life in patients with upper gastrointestinal symptoms. An improved evaluation of treatment regimens? AB - There is growing interest in measuring quality of life (QoL) in medicine. Together with objective variables such as healing rate, as recorded with endoscopy, this is believed to give a better basis for evaluation of treatment regimens in patients with upper gastrointestinal diseases. A strategy for the assessment of QoL in patients with upper gastrointestinal symptoms is presented here. The QoL evaluation was based on a battery of questionnaires, covering both general and specific aspects of life. General well-being was evaluated with the Psychological General Well-being Index (PGWB), and subjective symptoms with two specific questionnaires, the Gastrointestinal Symptom Rating Scale (GSRS) and the Ulcus Esophagitis Subjective Symptoms Scale (UESS). This new strategy was applied clinically in a study including 146 outpatients with suspected peptic ulcer. Initially, the patients reported a low degree of general well-being as evaluated with the PGWB, but the values returned to those found in normal populations within 4 weeks. Evaluation of the GSRS and UESS with regard to internal consistency, construct validity, and the ability to detect changes showed them to be satisfactory. The psychometric documentation of the measures indicates that they may give reliable and clinically valid information when used for evaluation of medical treatments in upper gastrointestinal disease. Further documentation of the methods is, however, needed to establish a generally acceptable QoL assessment in gastroenterology. PMID- 8210983 TI - Distribution of collagen types I, III, and IV in peptic ulcer and normal gastric mucosa in man. AB - The quality of peptic ulcer healing does not only mean complete epithelial restitution of the mucosal surface but also adequate repair of the underlying connective tissue. To obtain more information about the metabolism of extracellular matrix proteins in gastric mucosa and submucosa, we investigated biopsy specimens from six patients with antral peptic ulcers and six normal controls by staining of collagen types I, III, and IV with an immunofluorescence technique. In normal mucosa we found a certain amount of collagen types I and III in equal distribution and almost no collagen type IV. In contrast, there was a remarkable increase of collagen types I and III in peptic ulcers predominantly located at the ulcer edges. These results are compatible with the view that extracellular matrix proteins play some part in the ulcer healing process. PMID- 8210984 TI - Helicobacter pylori infection and exaggerated gastrin release. Effects of inflammation and progastrin processing. AB - Helicobacter pylori infection is associated with exaggerated gastrin release. We investigated whether this abnormality was due to the bacteria or the immune response. Fasting and meal-stimulated 'total' and amidated gastrin were measured in 10 H. pylori-infected volunteers before eradication therapy, after 2 and 14 days of therapy, and 4 weeks after completion of therapy. The exaggerated meal stimulated gastrin concentration remained unchanged after 2 days of therapy, although the polymorphonuclear cell infiltrate and H. pylori bacteria were no longer evident. The expected fall in gastrin concentration after 14 days of therapy was associated with a reduction in the density of mucosal mononuclear cells, suggesting exaggerated gastrin release was related to chronic inflammation or to H. pylori or its products. The effect of H. pylori on normal progastrin processing was also assessed; 2 control groups were included: 10 H. pylori uninfected volunteers and 13 patients with H. pylori peptic ulcers. There was a significant difference in the proportion of circulating gastrins that were biologically active amidated gastrins between ulcer patients and uninfected controls (56.7 +/- 4% versus 33.8 +/- 4%, p < 0.001). The proportion of amidated to total gastrins did not increase after successful eradication. PMID- 8210985 TI - Incidence and characteristics of pouchitis in the Kock continent ileostomy and the pelvic pouch. AB - The incidence, the median time to first appearance, and the clinical pattern of pouchitis were prospectively studied in 180 patients operated on for ulcerative proctocolitis with a continent ileostomy (CI; 84 patients) and a pelvic pouch (PP; 96 patients). Median follow-up for CI patients was 8.5 years (range, 2-15 years) and for PP patients, 5 years (range, 1-8 years). Pouchitis, with symptoms severe enough to require treatment, developed in 33% (28 of 84) of CI and 47% (45 of 96) of PP patients. The cumulative risk of developing one or more episodes of pouchitis over a 5-year follow-up was 34% in CI patients and 51% in PP patients. The median time to first appearance of pouchitis was 5 and 12 months, respectively. Eighty-six per cent of CI patients with pouchitis (24 of 28) and 71% of PP patients (32 of 45) experienced their initial episode within the first 2 years. Sixty-four per cent (18 of 28) of the CI patients and 76% (34 of 45) of PP patients had one single or a few short-lasting episodes of pouchitis with various symptom-free intervals, whereas 18% of patients in each group (5 of 28 CI patients, 8 of 45 PP patients) had frequent relapses. Most of these patients responded promptly to metronidazole treatment. Eighteen per cent (5 of 28) of CI patients and 6% (3 of 45) of PP patients had long-lasting episodes with a poor response to treatment. In this long-term study the pouch inflammation proved eventually to be Crohn's disease in four patients (2.2%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210986 TI - Cyclosporin A retention enemas in refractory distal ulcerative colitis and 'pouchitis'. AB - The aim of this study was to evaluate the use of cyclosporin enemas in patients with distal ulcerative colitis and 'pouchitis' resistant to all conventional medical therapy. In an trial 12 patients with distal ulcerative colitis unresponsive to treatment with topical and oral corticosteroids, 5-aminosalicylic acid, and oral immunosuppressive therapy together with 1 patient with 'pouchitis' unresponsive to repeated courses of antibiotics, topical corticosteroids, and oral mesalazine received 250 mg cyclosporin administered daily as a retention enema. Changes in symptoms and the sigmoidoscopic/histologic appearances of the rectal mucosa were assessed at monthly intervals. Seven of 12 patients with ulcerative colitis improved. There was a strong correlation between clinical and histologic improvement (p < 0.005). Four of 12 patients showed no response. Three of these required colectomy, two of whom had more extensive disease than had previously been documented. The patient with pouchitis showed improvement in symptoms and 'pouchoscopy' appearance but not in histologic score. Cyclosporin blood concentrations were very low and side effects negligible. Cyclosporin A retention enemas are safe and may be useful in the treatment of severe refractory distal ulcerative colitis. A controlled trial would now seem warranted. PMID- 8210987 TI - Is Helicobacter pylori involved in the pathogenesis of the gastritis characteristic of pernicious anaemia? Comparison between pernicious anaemia relatives and duodenal ulcer relatives. AB - The aim of the study was to evaluate whether Helicobacter pylori could be involved in the early stages of the severe corpus atrophy that is characteristic of overt pernicious anaemia and is usually H. pylori-negative. The behaviour of H. pylori infection and chronic gastritis was studied in 159 first-degree relatives of pernicious anaemia (PA) probands and was compared with that in 137 first-degree relatives of duodenal ulcer (DU) probands. DU is as a rule associated with H. pylori infection. PA relatives showed a markedly higher prevalence of severe corpus atrophy and of parietal cell antibodies than DU relatives. However, the prevalences of H. pylori did not show significant differences between the two groups of relatives. The age-specific prevalences of H. pylori infection increased similarly in both series of relatives up to geriatric age, together with an increase in the mean scores of corpus gastritis. However, in older age the prevalence of H. pylori in PA relatives showed a marked decrease, in spite of the increase in the mean gastritis score. The present result suggests the possibility that H. pylori is involved in the early PA stages that lead to severe corpus atrophy. The later progress of gastritis seems to be dependent on factors other than H. pylori, most likely 'autoimmune' mechanisms. PMID- 8210988 TI - Contraction and evacuation of the gallbladder studied simultaneously by ultrasonography and 99mTc-labeled diethyl-iminodiacetic acid scintigraphy. AB - Emptying of the gallbladder was studied by the simultaneous use of 99mTc-labeled diethyl-iminodiacetic acid [HIDA] scanning and real-time ultrasonography. In response to a liquid test meal the gallbladder volume was reduced for 80 min and then increased again, but the radionuclide evacuation continued and was more complete than could be explained by the reduction of gallbladder volume. In response to intravenous infusion of cholecystokinin, a maximal contraction of the gallbladder to 35% of the basal volume was obtained at 40 min, and 36% of the HIDA then remained in the gallbladder. In a separate series repeated intravenous injections of 99mTc-HIDA were given after the test meal, and the isotope was found to enter the gallbladder even when the gallbladder contracted. The results support the view that the gallbladder acts like a 'bellows' when contracting and that postprandial fluid secretion by the gallbladder mucosa may help to evacuate its contents. PMID- 8210989 TI - Effect of synthetic protease inhibitor on histologic changes and free radical activity in hamsters with pancreatic cancer. AB - To investigate the effects of synthetic trypsin inhibitors on pancreatic cancer, camostat (FOY-305) was administered orally to hamsters with experimental pancreatic cancer induced by diisopropanol nitrosamine (DIPN). The effect of free radicals on carcinogenesis was examined by measuring the tissue levels of the scavengers superoxide dismutase (SOD) and glutathione peroxidase (GSX-Px), and pancreatic tissues were examined histologically. Cancers developed in all hamsters that survived 24 weeks in the DIPN group and the FOY group, but 80% of the cancers in the DIPN group were tubular adenocarcinomas, and 91% of those in the FOY group papillary adenocarcinomas. The SOD activity in the DIPN group was significantly lower in the cancerous area and the borderline region than in the non-cancerous region and normal tissue. SOD activity in the cancerous and borderline regions was higher in the FOY groups than in the DIPN group. GSH-Px levels in the borderline and non-cancerous regions were significantly higher in the FOY group than in the DIPN group. These results suggest that the synthetic protease inhibitor slows the progress of pancreatic cancer by its free radical scavenging activity. PMID- 8210990 TI - The effect of antireflux operations on lower oesophageal sphincter tone and postprandial symptoms. AB - To elucidate potential mechanism(s) behind the mode of action of antireflux operations, the basal tone of the lower oesophageal sphincter and the relaxation after water swallows were studied before and after either a total fundic wrap (n = 25), highly selective vagotomy combined with fundoplication (n = 38), or insertion of an Angelchik prosthesis (n = 9). The basal tone preoperatively was similar in the three study groups, as was the relaxation that ensued on water swallows (nadir pressure). The fundic wrap increased the basal pressure in the lower oesophageal region from 13.0 +/- 2.3 (SE) to 21.2 +/- 2.4 mm Hg (p = 0.01), and insertion of the prosthesis around the sphincter had a similar effect (from 10.2 to 19.3 mm Hg). However, the combined vagotomy and fundic wrap procedure did not significantly change the basal pressure recordings (13.9 to 14.3 mm Hg). The mean nadir pressure after water swallows increased significantly postoperatively in all study groups. Patients with fundoplication and highly selective vagotomy relaxed their lower oesophageal sphincter less than patients with fundoplication only (p < 0.05). Similar results were obtained in patients who had an Angelchik insertion, although this did not reach statistical significance. These results suggest that the fundic wrap functions in part as a mechanical external compression and that the vagus nerve contributes to the ability of the postoperative high-pressure zone to relax on swallowing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210991 TI - Evaluation of a computer-based diagnostic score system in the diagnosis of jaundice and cholestasis. AB - A prospective series of 220 patients with jaundice and/or cholestasis was analysed by means of discriminant analysis to evaluate the diagnostic value of various symptoms and signs and basic hepatopancreatobiliary laboratory tests in the differential diagnosis of these patients. In addition, a computer-based diagnostic score (DS) system was developed and compared with the diagnostic value of clinical evaluation (CE), ultrasound (US), computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP). A multivariate stepwise discriminant analysis showed five independent diagnostic factors in distinguishing extrahepatic and intrahepatic diseases: duration of jaundice (p = 0.002), serum protein concentrations (p = 0.002), Normotest (p = 0.04), fever during the past 3 months (p = 0.54), and age (p = 0.58). To sum up the contributions of independent factors, a DS was developed. The discrimination function was as follows: duration of jaundice x 0.97 + age x -0.40 + fever during the past 3 months x 0.33 + serum protein concentration x 0.35 + Normotest x 0.27. The diagnostic sensitivity of DS in the detection of extrahepatic disease was 96%, with a specificity of 80% and an efficiency of 93%. The sensitivities of the imaging methods (62-85%) were inferior to that of DS, whereas the specificities were better (94-98%). The sensitivity of CE was only slightly lower (86%) than that of DS, but the specificity was lowest (57%). In conclusion, relatively few (5 of 40) of the classical symptoms, signs, and biochemical tests proved to be independent diagnostic factors in distinguishing extrahepatic and intrahepatic diseases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8210992 TI - Dissolution of cholesterol gallbladder stones with methyl tert-butyl ether in patients with increased surgical risk. AB - The safety and efficacy of methyl tert-butyl ether (MTBE) dissolution of cholesterol gallbladder stones were evaluated in 25 patients with increased risk for surgery. Two patients were treated twice. The MTBE was infused and aspirated manually through a percutaneous transhepatic catheter to the gallbladder. The placement of the catheter failed in three patients (11%). In 19 of 24 patients (79%) there was complete dissolution of stones after a mean treatment time of 12.2 h (range, 4.3-19.5 h). In five patients treatment was discontinued before complete dissolution owing to technical problems or side effects. Side effects were nausea, pain, vasovagal reaction, and fever. Fifteen patients were followed up for a mean of 15.7 months after dissolution. Stone recurrence was found in eight patients, five of whom suffered symptomatic relapse. We conclude that dissolution therapy with MTBE is a safe and adequate alternative to surgery in selected high-risk patients. PMID- 8210993 TI - Pancreatic extracts are necessary for the absorption of elemental and polymeric enteral diets in severe pancreatic insufficiency. AB - Tube feeding nutrition, either elemental or polymeric, is increasingly used in patients with digestive problems. Pancreatic insufficiency is a widely accepted indication for the use of an elemental formula, which requires less residual digestive capacity. To confirm this assumption, we have compared the absorption of elemental and polymeric diets and the effect of exogenous pancreatic enzymes in a patient on long-term total enteral feeding after total pancreatectomy. Malabsorption of both formulas was observed without enzyme supplementation. A marked improvement of fat and nitrogen absorption was obtained when pancreatic enzymes were added to both enteral diets. It is concluded that pancreatic enzymes should always be added to liquid diets in pancreatic insufficiency. No clear advantage is to be anticipated by the use of elemental as compared with polymeric diets. PMID- 8210994 TI - The Nobel Lectures in Immunology. The Nobel Prize for Physiology or Medicine, 1987. Somatic generation of immune diversity. PMID- 8210995 TI - Expression of secreted immunoglobulin heavy chain genes and immunoglobulin secreting cells in human lymphocytes. AB - The numbers of immunoglobulin-secreting cells in peripheral blood mononuclear cells and the expression of mRNA for secreted type of immunoglobulin heavy chains were investigated in healthy children, compared with the percentages of surface immunoglobulin-bearing cells and the expression of mRNA for membrane-bound type of immunoglobulin heavy chains, respectively. Although a difference between expression of mu s mRNA and mu m mRNA was unclear, mu mRNA was well transcribed. The expression of gamma s mRNA or alpha s mRNA was markedly higher than that of gamma m mRNA or alpha m mRNA. However, although the detection methods could be of different sensitivities, the percentage of IgM-, IgG-, or IgA-secreting cells was markedly low, compared with the percentage of surface IgM-, IgG-, or IgA-bearing cells, respectively. Therefore, additional regulation of the pattern of the immunoglobulin gene expression may be exerted at the translational and post translational stages. PMID- 8210996 TI - A subset of V delta 1+ T cells proliferates in response to Epstein-Barr virus transformed B cell lines in vitro. AB - It has previously been shown that murine tissue derived T-cells expressing the gamma delta T-cell receptor can respond to autologous (stressed) cells implying the recognition of an autoantigen. Here we report that a large proportion of human synovial tissue and peripheral blood derived V delta 1+ gamma delta T-cell clones proliferate in response to stimulation with autologous and allogeneic EBV transformed B-lymphoblastoid cell lines (LCL). In contrast, V delta 1- gamma/delta and alpha/beta TCR+ T-cell clones isolated from the same tissue samples did not display proliferation towards the LCL. The proliferative response of these V delta 1+ clones was dependent on contact between responder and stimulator cells and could be blocked by a MoAb to LFA-1 and by antibodies to the gamma delta TCR/CD3 complex. Because the responses of these clones to LCL cells appear to be independent of the gamma-chain co-expressed with the V delta 1-chain these resemble a superantigen response. The capacity of this subset of V delta 1+ T-cell clones to proliferate after stimulation with LCL may imply the recognition of an endogenous epitope. Moreover, since so far we have been able to isolate only LCL reactive gamma delta T-cell clones from synovial tissue and peripheral blood of reactive arthritis patients and not from peripheral blood of healthy individuals, the frequency of such 'autoreactive' gamma delta cells may be higher in these patients. PMID- 8210997 TI - Histocompatibility complex gene products and exposure to oestrogen: two independent disease accelerating factors in murine lupus. AB - A number of studies have demonstrated that oestrogen exerts a significant impact on the course of experimental autoimmune diseases. Exposure to oestrogen aggravates SLE glomerulonephritis whereas the opposite outcome has been demonstrated in experimental arthritis, vasculitis, thyroiditis, and sialadenitis. In this report we have analysed the respective impact of H-2z linked gene products and long-term treatment with physiological doses of oestradiol on clinical and immunological variables in castrated backcrosses of lupus prone NZB/W and NZB mice. Our results demonstrate that H-2z linked gene products accelerate B-cell activation and stimulate autoantibody production resulting in aggravation of glomerulonephritis and precocious death in renal failure. These H-2z linked gene products do not influence T-cell mediated sialadenitis. Irrespectively of the H-2 haplotype of the mice, administration of oestrogen resulted in intense polyclonal B cell activation and aggravation of glomerulonephritis. However, exposure to oestrogen resulted in amelioration of sialadenitis. Notably, our result indicates that B-cell activation achieved by oestrogen and H-2z gene linked products, respectively is mediated by independent mechanisms. In addition, we have developed a predictive in vivo test that permits forecasts regarding efficiency of oestrogen treatment for suppression of T-cell mediated lesions. Using this test procedure in young, clinically healthy SLE mice we have been able to prove that animals displaying suppressed delayed type hypersensitivity (DTH) after short-term oestrogen exposure showed significantly lower long-term morbidity regarding development of sialadenitis upon continuous treatment with physiological doses of oestradiol. PMID- 8210998 TI - Expression of a mast cell tryptase in the human monocytic cell lines U-937 and Mono Mac 6. AB - Expression of a mast cell tryptase mRNA was detected in two human monocytic cell lines, the U-937 and the Mono Mac 6, and in normal human peripheral blood (PB) monocytes. In the U-937 cell line but not in normal PB monocytes, the tryptase expression was upregulated 3-50 fold following phorbol ester (PMA)-induced differentiation, but no such induction was seen after retinoic acid, interferon gamma or vitamin D3 exposure. The tryptases expressed in PMA-induced and non induced U-937 and in Mono Mac 6 were characterized by PCR amplification and nucleotide sequence analysis. The U-937 cell line was found to express a tryptase identical to one of the previously cloned mast-cell beta tryptases (Tryptase I), and the tryptase expressed in Mono Mac 6 was found to be nearly identical to the previously cloned alpha tryptase. By northern blot analysis with oligonucleotide probes specific for the alpha and beta tryptases both cell lines were found to express only one type of tryptase. Densitometric quantifications of tryptase mRNA levels, in the two cell lines, showed approximately 80 times higher mRNA levels in Mono Mac 6 compared to non-induced U-937. Immunohistochemical staining for tryptase showed a marked heterogeneity in the Mono Mac 6 cell line. Only one out of 10 cells were positive for the protein but the levels in these cells were very high, equivalent, or even higher than the levels seen in the human mast cell line HMC-1. This shows that the expression of a single tryptase, in this case the alpha tryptase, is sufficient for the production of a stable protein and probably also a stable proteolytically active tetramer. The family of human mast-cell tryptases has been considered to represent a class of proteases specifically expressed in mast cells and basophilic leucocytes. The expression of tryptases in two monocytic cell lines and in normal PB monocytes indicate that in humans, the lineage specificity of these serine proteases is less restricted than earlier expected. The cloning of a full length cDNA for the murine counterpart to the human mast cell tryptases, the MMCP-6, is presented. No expression of the MMCP-6 was detected in a panel of mouse monocyte or macrophage cell lines indicating a species difference in the lineage specificity of the 'mast cell tryptases'. PMID- 8210999 TI - The influence of LFA 1 on human T cells stimulated by solid-phase immobilized HLA class II-peptide complexes. AB - Purified HLA class II-peptide complexes immobilized to a solid support induce proliferation of human T-cell clones, indicating that human T-cell clones can proliferate in the absence of secondary signals from accessory cells. We hypothesized that T cells can provide co-stimulatory signals to T cells. LFA-1 molecules play an important role in homotypic interactions of T cells and murine monoclonal antibodies reactive with LFA 1 can inhibit T cell-T cell interactions. LFA-1 reactive monoclonal antibodies inhibited cytolysis of peptide-pulsed T cells by T cells and partially inhibited T-cell proliferation. To study the direct effect of the LFA 1 molecule on T-cell activation, we co-immobilized HLA class II-peptide complexes with LFA-1 reactive MoAbs. Co-immobilization resulted in an enhanced proliferative response of the T-cell clones. This could indicate that the LFA 1 molecule on T cells is not a passive adhesion molecule, but is capable of transducing a signal that synergizes with the stimulatory signal via the T-cell receptor. PMID- 8211000 TI - Characterization of a multimeric polypeptide complex on the surface of thymus derived cells in the Mexican axolotl. AB - We previously raised a rabbit antiserum (L12) against a 38 kD polypeptide which is expressed on the surface of thymocytes and peripheral T cells of an Urodele Amphibian, the Mexican axolotl (Ambystoma mexicanum). Here we show that L12 antibodies immunoprecipitate several labelled molecules from surface iodinated axolotl spleen cells, including the 38 kD molecule, but also two polypeptides of 43 and 22 kD which are covalently linked to other elements. Another rabbit antiserum (L10) was raised against detergent-solubilized axolotl thymocyte membranes and shown to recognize the majority of thymocytes and about half of the splenocytes in immunofluorescence. In Western blotting, L10 antibodies recognized a limited number of surface polypeptides in thymocyte and splenocyte lysates, including 43, 38, and 22 kD elements. Immune complexes formed between L10 antibodies and solubilized splenocyte membranes were used to immunize BALB/c mice intrasplenically in the aim of raising MoAbs specific for axolotl T cells. Monoclonal antibody 87.16 was shown to stain in immunofluorescence 26.7% of thymocytes and 26.8% of spleen cells. This MoAb recognized a 43 kD polypeptide that can covalently associate on the T-cell surface with several other molecules to form a multimeric complex. PMID- 8211001 TI - Regulation of MHC class I membrane expression by beta 2-microglobulin. AB - MHC-I binding peptides and beta 2 microglobulin (beta 2-m) can upregulate the MHC I heavy chain expression on certain peptide transporter mutant cells. We have further studied this with normal cells and non-mutant cell lines. No MHC-I upregulation was seen with normal, resting or activated T cells. On mouse cell lines P815 and B16, both peptides and human beta 2-m gave an additive upregulation response. With the human small cell lung carcinoma H82, an optimal HLA.A2 binding peptide (GILGFVFTL) gave an upregulation response, whereas beta 2 m alone or in combination with this peptide had no effect. However, beta 2-m potentiated the response of H82 cells to a slightly longer peptide. Using mutant RMA-S cells, it was found that both Brefeldin A (BFA) and chloroquine, but not leupeptin, inhibited MHC-I upregulation response to both peptide and beta 2-m. In contrast to chloroquine, BFA also gave a reduction of background membrane MHC-I expression, presumably due to a block in Golgi transport. Human beta 2-m, which binds to RMA-S cells, and which is known to internalize into endosomes, did not reappear on the cell surface. When Db on RMA-S cells was upregulated by human beta 2-m, the sensitivity of these cells to Db restricted CTL cells increased. Even if beta 2-m did not upregulate the overall MHC-I expression on normal cells, it may still quantitatively increase the expression of optimally presented peptides and endosomal recycling many be important in this process. PMID- 8211002 TI - Antibodies to dsDNA are produced during primary BK virus infection in man, indicating that anti-dsDNA antibodies may be related to virus replication in vivo. AB - Experimental immunizations with both the Polyomavirus BK and with the isolated viral genomic dsDNA regularly induce antibodies with a relative affinity for BK virus dsDNA. In the present study we demonstrate that the anti-dsDNA responses to BK virus in experimental animals also appear during natural BK virus infection in man. Fifty-nine children were examined over time for serological signs of primary BK virus infection. Of eight children found to undergo primary infection with BK virus, anti-BK dsDNA antibodies appeared in all. In 4 of the 8 patients the antibodies cross-reacted significantly with mammalian dsDNA, and weak cross reactions were also noted in at least three other patients. The antibodies resembled those induced in the experimental model with regard to their relative affinity for BK dsDNA. In contrast, most, but not all, anti-dsDNA antibodies from 10 SLE patients cross-reacted extensively with dsDNA from viral and mammalian origin. Thus, a dsDNA virus like BK virus may provoke immunological intolerance to dsDNA, but, with qualities different from those produced during SLE. The present observations demonstrate that induction of anti-dsDNA antibodies is not restricted to experimental immunization of animals, but does also take place in humans during naturally acquired BK virus infection. The relevance of this model for the spontaneous production of anti-dsDNA antibodies is discussed. PMID- 8211003 TI - Human cord blood contains an IGM antibody to the 41KD flagellar antigen of Borrelia burgdorferi. AB - Natural antibodies are the IgM products of fetal and neonatal B cells. These are germline encoded low affinity antibodies with multiple specificities to self and exogenous antigens. Lyme borreliosis is the disease resulting from infection with the spirochete, Borrelia burgdorferi. The humoral response to this organism is brisk, directed at multiple proteins, and persistent. Antibody to the 41kd flagellar antigen is found early in disease, but may also be found in non-exposed individuals. These properties suggest that the anti-41kd antibody may be a natural antibody. We report here the finding of an IgM anti-41kd reactivity in 29% of cord blood samples from patients in an area non-endemic for Lyme disease. The results are consistent with the hypothesis that antibody to flagellin may be a germline encoded natural antibody, and could be important in the immunopathogenesis of Lyme arthritis and other arthritides. PMID- 8211004 TI - Postinfarction rupture of left ventricular free wall repaired with a glued-on pericardial patch. Case report. AB - In a 68-year-old man admitted in deep shock, prompt echocardiographic diagnosis of postinfarction left ventricular free wall rupture was followed by probably life-saving pericardiocentesis. At emergency surgery a 2 cm linear tear in the anterolateral wall of the left ventricle was successfully repaired with a glued on pericardial patch, without infarctectomy or placement of sutures in the infarcted area. PMID- 8211005 TI - Neurofibrosarcoma of the intrathoracic vagus nerve. Case report. AB - A rare case of neurofibrosuarcoma of the intrathoracic vagus nerve in a man with von Recklinghausen's neurofibromatosis is reported. Magnetic resonance imaging accurately demonstrated the tumour and its relations to surgically important structures. Resection, in accordance with general recommendations for such tumours, was successfully performed. PMID- 8211006 TI - Pulmonary endometriosis causing haemoptysis. Report of a case treated with lobectomy. AB - A 24-year-old woman with catamenial haemoptysis was treated with the antioestrogenic drug danazol for suspected pulmonary endometriosis. The haemoptysis then ceased, but rapidly recurred when the patient discontinued the medication 3 months later because of severe side effects. Lobectomy was performed, and the diagnosis histologically confirmed, 14 months after the onset of symptoms. Thereafter the patient was free from haemoptysis. PMID- 8211007 TI - Recent results with the modified Fontan operation. AB - From Jan 1989 to December 1991, 61 patients had modified Fontan procedures for a variety of lesions, including tricuspid atresia (18), mitral atresia (3), double inlet ventricle (14), isomeric hearts (4) and others (22). The hospital mortality was 1.6% (70% CL.0.2-5.3%). There were 2 late deaths. The median age at operation was 3.7 years (mean 5.6, range 1.5 to 20.3 years). There were two late failures at 2 months and 30 months after the operation, requiring take down of the Fontan in one and heart transplantation in the other. The 89% of the patients followed up are in NYHA class I or II at a mean follow up of 21.5 months (range 3-35 months). This suggests that the modified Fontan operation performed with the current patient selection criteria can be performed with a low mortality and that the early results are encouraging in the majority of the patients. PMID- 8211008 TI - Single lung transplantation in piglets. Technique and follow-up. AB - Single lung transplantation was performed in 21 piglets in order to develop a new experimental model for study of chronic rejection phenomena. In group I (unmodified rejection), acute rejection occurred in recipients which survived transplant and mean survival was 7 days. In Group II (triple immunodepression) the mean follow-up was 32 (0-134) days. Acute rejection was histologically detected in five of the 13 allografts and moderate to strong chronic vascular rejection in four. In group III (untreated autografts) the postoperative course was uneventful. The 60-day weight gain was 113% in group II, and 167% in group III. Computed tomography in group II showed 95% increase in allograft volume and 145% increase in contralateral lung volume (mean follow-up 102 days, n = 3). The corresponding gains in bronchial diameter were 39% and 40%. The piglet model allowed versatile monitoring of lung transplants, with manifestations of acute and chronic rejection providing valuable material for further studies. The significant recipient and allograft growth indicate that also children may be accepted as candidates for lung transplantation. PMID- 8211009 TI - Thromboplastin activities and monocytes in the coronary circulation of reperfused human myocardium. No effect of preoperative treatment with n-3 fatty acids. AB - In a double-blind study 18 patients were randomized to receive a daily dietary supplement of concentrated ethyl ester compound of n-3 fatty acids or placebo (corn oil) for at least 6 weeks before coronary bypass surgery. Three-fold increase of serum eicosapentaenoic acid and 20% reduction of triglyceride levels were found preoperatively in the n-3 group, while the two groups were similar as regards monocyte and platelet counts, mean platelet volume and monocyte activation as expressed by thromboplastin activities. For determination of transcardiac gradients, coronary sinus and aortic blood were sampled preoperatively 5, 10 and 30 minutes after release of the aortic cross-clamp. In both patient groups the monocyte count was lower in coronary sinus than in aortic blood at 5 and 10 minutes, but the differences were not significant. The platelet counts showed no significant change. In vitro stimulation of monocytes, however, evoked significantly (p < 0.05) less thromboplastin activity in coronary sinus blood than in aortic blood at all three sampling times, without significant intergroup difference. The monocytes most sensitive to activation presumably were trapped in the reperfused myocardium, and this sequestration was not hindered by pretreatment with n-3 fatty acids. PMID- 8211010 TI - Two-dimensional echocardiography for prediction of aortic valve prosthesis size. A comparative study of Medtronic-Hall and Carpentier-Edwards supra-annular valves. AB - To assess the value of two-dimensional echocardiography (2D ECHO) for predicting prosthetic aortic valve size, the diameter of the aortic annulus was measured before implantation of a Medtronic-Hall valve in 24 patients and a Carpentier Edwards supra-annular valve in 34. In the Medtronic-Hall group, the average prosthesis size was similar to the average annulus diameter, i.e. 23.2 +/- 2.1 vs 23.0 +/- 3.4 mm (NS), 95% confidence interval for the difference -1.0-0.7 mm. In the Carpentier-Edwards group the corresponding figures were 23.5 +/- 2.1 and 22.0 +/- 2.3 mm (p < 0.001), with 95% confidence interval 0.9-2.0 mm. Correlation between annulus diameter indicated by preoperative 2D ECHO and prosthesis size was stronger in the Medtronic-Hall (r = 0.88, p < 0.001) than in the Carpentier Edwards group (r = 0.73, p < 0.001). The authors conclude that prosthetic aortic valve size may be accurately predicted by 2D ECHO, with Medtronic-Hall valve size similar to, and Carpentier-Edwards prostheses on average 1-2 mm larger than the 2D ECHO-estimated annulus diameter. PMID- 8211011 TI - Doppler-derived pressure differences in normally functioning aortic valve prostheses. Studies in Bjork-Shiley monostrut and Biocor porcine prostheses. AB - To determine the normal range of maximum and mean Doppler-derived pressure differences for mechanical and bioprosthetic valves in the aortic position, Doppler echocardiography was performed on 239 stable patients with normally functioning Bjork-Shiley monostrut (BSM, n = 185) or Biocor porcine (n = 54) prostheses. The interval from aortic valve replacement to echocardiography was 3 9 days. Maximum and mean pressure differences were significantly greater in 21 mm than in 25 or 27 mm BSM prostheses. The pressure differences in 23 mm BSM valves did not diverge significantly from those in 21, 25 or 27 mm valves. The mean pressure difference did not exceed 30 mm Hg in any type or size of studied prosthesis. No significant differences were found in pressure gradients in comparisons between BSM and Biocor prostheses of corresponding sizes. The calculated velocity ratio for BSM prostheses was not significantly influenced by the valve size. We suggest that the normal range of Doppler-derived maximum and mean pressure differences determined in this study be adopted as reference in evaluations of aortic BSM and Biocor valve prostheses. PMID- 8211012 TI - Composite graft replacement of the aortic valve and ascending aorta with Cabrol technique. AB - Replacement of the aortic valve, root and ascending aorta with the technique first described by Cabrol was performed on 17 patients. In five cases the aortic arch was also replaced. The indications were type A aortic dissection with aortic insufficiency (8 cases, with acute dissection in 7), native endocarditis with severe aortic insufficiency and aortic root abscess (3 cases), prosthetic endocarditis (3), and true aneurysm of the ascending aorta with aortic insufficiency (3). Acute surgery was performed in 15 cases (88%). The overall operative mortality was 41%. For the patients discharged from hospital the mean observation time was 30 months. None died, but in one case the right leg of the interposition graft became occluded and reoperation was required 40 months after the primary operation for acute type A dissection. The described technique of aortic valve and root displacement can be used in all cases in which use of a composite graft is indicated, except in situations where the coronary ostia and arteries are damaged by acute dissection. PMID- 8211013 TI - [Surgery for arrhythmia in patients with therapy-resistant ventricular tachycardia]. AB - We reviewed the data of 42 consecutive patients (mean age 55 +/- 12 years) who underwent surgery for control of recurrent drug-refractory ventricular arrhythmia. A history of myocardial infarction was present in 38 patients, 4 patients had congenital heart disease (2 aneurysms, 1 right ventricular dysplasia, 1 hamartoma). The mean LV ejection fraction was 40 +/- 14%. At preoperative electrophysiologic study, ventricular tachycardia was inducible in 32 of 33 patients. The mean heart rate was 188/min. A mean of 3.3 +/- 2.1 antiarrhythmic drug trials were ineffective. The most frequently performed surgical procedure (n = 36) was visually guided subendocardial resection, alone or in combination with cryothermal ablation. In 30 patients additional aneurysmectomy was performed. A mean of 1.9 +/- 1.4 coronary arteries in 32 patients were bypassed. The overall in-hospital mortality (30 days) was 9.5% (1 arrhythmic death, 1 pump failure, 1 sepsis, 1 hemorrhagic shock). We found 2 significant (p < 0.05) predictors of perioperative mortality: recent myocardial infarction and patient's age. During a mean follow-up of 33 months (range 1 to 90), there were 3 sudden cardiac deaths and 6 nonfatal recurrences of ventricular tachycardia which were subsequently prevented with antiarrhythmic drug therapy. Thus, the overall success in control of arrhythmia was 92%, in 59% by surgery alone. Survival was 79% at 2 years after surgery and 63% at 5 years. We conclude that patients who have successful subendocardial resection and aneurysmectomy for control of ventricular arrhythmia have an excellent chance of arrhythmia-free survival and a relatively good prognosis. PMID- 8211014 TI - [Prognosis and epidemiology of malignant hemangioendotheliomas of the thyroid gland]. AB - Five new cases of malignant hemangioendothelioma of the thyroid are reported. This rare malignant tumor is described predominantly in regions with endemic goiter such as the Alpine zone. The estimated incidence of the disease is between 0.15 and 0.25 per 100,000 inhabitants per year for Western Austria. Two of the five patients were heavily exposed to vinyl chloride occupationally for 9 and 30 years respectively. Surgically, a R-0 resection was performed in two patients, R 1 in two, and R-2 in one patient. Postoperative radiotherapy was given in four cases. The tumor doses were between 58 and 65 Gy. Three patients received the sensitizer razoxane in addition. Local tumor control was achieved in 4 of 5 patients. The survival times of the 5 patients were 78, 68+, 38+, 7.5 and 3 months. Two patients are still alive after 68 and 38 months. This small series may indicate that the outcome of the disease may not be uniformly deleterious and the resistance to radiotherapy reported in the literature [3, 10] is debatable. PMID- 8211015 TI - [A trial of modified triple therapy for the eradication of H. pylori in recurrent duodenal ulcer]. AB - In a prospective trial we examined the efficacy and acceptability of a modified triple therapy in H. pylori (HP)-positive patients with recurrent duodenal ulcer disease. Oral administration of amoxicillin for two weeks was substituted for one single injection of intramuscular depot penicillin (benzathine penicillin G). Additionally, patients were given ornidazole 500 mg tid for 14 days and 120 mg colloidal bismuth sub-citrate qid for 28 days. The patients were investigated for H. pylori colonization using a rapid urease test (CLO), histology (H&E-, Giemsa stain), culture (including determination of the minimal inhibitory concentrations for metronidazole, penicillin G and amoxicillin) and H. pylori serology (Cobas Core Anti-H. pylori EIA, F. Hoffmann-La Roche). Control endoscopies using the same methods were performed 1 and 6 months after eradication therapy. The eradication rate was 50% and the ulcer healing rate 90% 1 month after therapy. Ulcers recurred in 2/3 of patients with persistent infection vs 0/5 of HP eradicated patients after 6 months. Both successfully HP-eradicated patients and patients with treatment failure exhibited comparable decreases in mean serum IgG anti-HP concentration within 2 months. Discrimination between the two groups and hence identification of the eradication success by serology was not possible within a time period of 2 months. After 6 months, serum IgG anti-HP concentrations in non-HP-eradicated patients returned to pre-therapy values, in HP-eradicated patients the concentrations further decreased. The above-described modified triple therapy against HP cannot be recommended as a standard therapy, mainly because of the insufficient eradication effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8211016 TI - [Unexpected thrombocytopenia in newborn infants]. AB - Severe thrombopenia of the newborn involves appreciable morbidity and mortality. Effective treatment exists for all forms of neonatal thrombopenia. Swiftest possible correction of thrombopenia must be the prime aim of all measures. Delaying of effective treatment due to workup must be avoided. If there is suspicion of nAIT, effective results have been achieved with transfusion of irradiated and washed maternal thrombocytes, and with immunoglobulin therapy in the case of suspected thrombopenia due to maternal autoantibodies (ITP or SLE). Transfusion of unselected thrombocytes is the therapy of choice in non-immune thrombopenia, and in immune thrombopenias it serves as an emergency measure if there is a high bleeding risk. PMID- 8211017 TI - [Fetal and neonatal alloimmune thrombocytopenia]. AB - Alloimmune thrombocytopenia (AIT) in fetuses and newborn, a disease resembling Rh incompatibility, is caused by transplacental transfer of an IgG-class antibody against fetal platelets. In humans five different platelet antigen systems are so far known which lead to AIT. The disease occurs in 1:2000-1:5000 deliveries. In contrast to Rh disease, immunization occurs in the first pregnancy in the majority of cases. The main significance of AIT lies in the occurrence of fetal ( 10%) and neonatal (-20%) intracranial hemorrhage. Newborns are treated with compatible platelets, if necessary in combination with immunoglobulins. The high rate of fetal intracranial hemorrhage justifies therapy during pregnancy as well. Antenatal measures include treatment of the mother with high-dose immunoglobulin, treatment of the fetus with immunoglobulin by cordocentesis, and fetal platelet transfusions. However, all therapeutic measures involving the fetus remain in the experimental stage at present. International cooperative studies are necessary to evaluate cost-benefit of intervention during pregnancy. PMID- 8211018 TI - [Problems in the classification of thyroid tumors. Their significance for prognosis and therapy]. AB - Standardized nomenclatures of tumors are mandatory for epidemiological investigations as well as for the correct interpretation of pathological diagnoses by the clinician. Not least thanks to the activity of the World Health Organization (WHO), uniform tumor nomenclatures in worldwide use have been adopted for most organs. This applies also for the thyroid, even in Switzerland, where many pathologists had formerly been convinced that only the special and rather complicated nomenclature of Langhans, adapted by Wegelin, was consistent with the special tumor situation in Switzerland, a former endemic goiter area. The simplified classification of WHO is demonstrated for the group of malignant tumors of the thyroid and the problems concerning their classification are discussed. Difficulties of classifications arise in well differentiated tumors rather than in undifferentiated, anaplastic forms. For example, it is not possible to assess unequivocally the malignancy of strongly encapsulated forms of highly differentiated follicular tumors. They are then called, rather evasively, "atypical adenomas". The difficulties do not lie in the system of classification but in the tumor's specific manner of growth, and the clinician should be aware of this. Otherwise he may overstrain the diagnostic potentialities of his pathologist. PMID- 8211019 TI - [Spondylogenic cervical myelopathy: conservative and surgical therapy]. AB - The symptoms and signs of spondylotic cervical myelopathy (SCM) in the elderly are variable, but an ataxic-spastic gait disturbance combined with tingling in the finger tips and clumsy hands are often encountered. SCM is due to degenerative changes of discs and osseous and ligamentous structures with compression of the spinal cord. The symptoms, signs, surgical and conservative treatment, and outcome were retrospectively analyzed in 36 patients. Most of the patients undergoing surgery (n = 22) improved their clinical score and maintained this improvement for the period of observation; the non-operated patients (n = 14) had a very slow progression. Diagnostic difficulties and problems of the surgical and conservative approaches are discussed. PMID- 8211020 TI - [An epidemic of typhoid fever]. AB - An outbreak of typhoid fever was observed in a group of students and accompanying teachers during a journey to Haiti in summer 1991. All (6) infected persons were symptomatic and rapidly cured by antibiotics. The Salmonella typhi strains isolated from blood cultures were all identical by ribotyping. All the participants had a medical checkup and stool cultures were obtained; asymptomatic carriers could be excluded. Secondarily infected persons were not observed. The infectious source has not been identified, but various hypotheses are considered. Oral vaccination does not appear to modify the risk of infection in exposed persons. PMID- 8211021 TI - [Trans-jugular intrahepatic portosystemic stent-shunt (TIPS) in a patient with Budd-Chiari syndrome]. AB - The surgical modalities for the management of Budd-Chiari syndrome are associated with high morbidity and mortality. The clinical course of a patient with subacute Budd-Chiari syndrome and a myeloproliferative disorder is described in whom, to reduce the portal hypertension, a transjugular intrahepatic portosystemic stent shunt (TIPS) was implanted. TIPS is a new, still experimental procedure for the treatment of patients with portal hypertension which is used mainly for patients with recurrent variceal bleeding. An intrahepatic metal wire stent connects a main branch of the portal vein with a large hepatic vein and reduces the portal venous pressure as a side-to-side portosystemic shunt. In the patient described here the implantation of a TIPS was followed by rapid reduction of ascites production and a continuing general improvement. PMID- 8211022 TI - [ARDS and mechanical ventilation--"primum nil nocere"]. AB - Present evidence demonstrates that mechanical ventilation in patients with adult respiratory distress syndrome (ARDS) contributes to the ongoing pulmonary damage, a condition known as "ventilator lung". Data from various animal studies indicate that volume, rather than pressure, is probably the main culprit. Accordingly, clinicians should use tidal volumes smaller than those usually recommended. This approach leads to hypercapnia (i.e. so-called "permissive hypercapnia"), which seems to have very few adverse effects and might even be beneficial. Moreover, there is an added risk of atelectasis, which can be prevented by the application of positive end-expiratory pressure (PEEP). The present study reviews the pathophysiological mechanisms by which mechanical ventilation is injurious to the lung, and attempts to outline an approach aimed at minimizing such damage. PMID- 8211023 TI - [Therapeutic plasmapheresis--a critical review in the light of the current literature]. AB - For centuries it has been the dream of many physicians to cure illnesses by eliminating disease provoking substances which are thought to circulate in the human body. Technical developments during the past 20 years have made therapeutic plasma exchange (TP) a useful procedure for clinical application. Because of the lack of well controlled studies the true benefit of the method remains speculative in many clinical situations. Since the report of the American Medical Association (AMA) Panel on Therapeutic Plasmapheresis in 1985 several controlled studies on this subject have been published in recent literature; they are reviewed in this article. In summary, TP seems justified only in some area and well defined situations such as thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, acute and severe myasthenia gravis, severe Guillain-Barre syndrome, hyperviscosity syndromes such as hyper- and paraproteinemia, and in several intoxications and metabolic disorders such as Refsum disease or hereditary hyperlipidemia type IIa. PMID- 8211024 TI - [Pravastatin in the treatment of primary hypercholesterolemia: a Swiss multicenter study]. AB - Conventional lipid-lowering agents displayed only limited efficacy in lowering total and LDL cholesterol and a high incidence of side effects. Pravastatin is a new potent cholesterol-lowering agent, which selectively inhibits hepatic HMG-CoA reductase. In a double-blind, placebo-controlled Swiss multicenter study with determination of lipids and lipoprotein in a central laboratory, the efficacy and safety of 6 months' therapy with pravastatin was evaluated in 50 patients with mild hypercholesterolemia and additional coronary risk factors. Compared to baseline and after 26 weeks' therapy, pravastatin significantly reduced total cholesterol (pravastatin vs placebo, -17% vs +7%, p < 0.0001) and LDL cholesterol (-26 vs +2%, p < 0.0001). The total/HDL cholesterol ratio ( = "atherogenic index") was comparable in the two groups at baseline (5.9 +/- 1.1 vs 6.3 +/- 0.9), and was distinctly lowered by pravastatin but not placebo (-20 vs 0%, p < 0.0001). In 11 patients in whom the reduction of serum total cholesterol after 13 weeks' treatment with 20 mg pravastatin was still below target (on average 9.1%), doubling of the dose produced a further decrease of 4.3%. Serum HDL cholesterol and serum triglyceride levels did not change significantly during pravastatin treatment as compared to baseline and placebo. Pravastatin was well tolerated during the 26 weeks without relevant subjective side-effects. There were 5 dropouts during the study, 2 patients in the pravastatin group and 3 in the placebo group. These findings document that pravastatin, administered in a single daily dose of 20 to 40 mg, effectively lowers serum cholesterol and total /HDL-cholesterol improving action and is well tolerated. PMID- 8211025 TI - [Effect of inpatient treatment on pulmonary findings and subjective well-being of patients with chronic bronchitis]. AB - In a prospective study, inpatient therapy results (mean duration of hospitalization 27.3 days) has been assessed in 70 patients with COPD (mean age 62.4 years). Therapeutic success was observed in the objective pulmonary parameters (an increase of FEV1 from 50.5% to 57.6%, p < 0.001) and an increase in PaO2 from 7.7 kPa to 8.5 kPa (p < 0.001) as well as an improvement in life quality established by questionnaire. The best pulmonary results were achieved by patients with least pulmonary obstruction and by those with subjective well-being on entry. Women and younger patients experienced the biggest improvement in life quality. Furthermore, there was a correlation between coping with chronic bronchitis and subjective well-being. Importantly, no correlation between changes in the objective pulmonary parameters and changes in well-being was observed; a finding which puts in question the previous rating of inpatient therapy success in COPD. PMID- 8211026 TI - [Endoscopic, biopsy and functional results in irradiated esophageal carcinoma]. AB - 83 patients of average age 64 (36-86) years with esophageal cancer were irradiated according to a prospectively defined treatment concept. After 60 Gy, re-endoscopy with biopsy was scheduled. If the tumor was still macro- or microscopically described, a boost to 70 Gy was given. During consistent weekly monitoring particular attention was focused on patients' ability to feed themselves. While initially only 7.2% could swallow solid food, by the end 84% of patients with a radiation dose of 60 Gy or more reported normal daily eating. Patients in whom the tumor was no longer present endoscopically or histologically survived four times longer (13.5 months) than those with persistent malignoma. PMID- 8211027 TI - [Cervical lymphadenitis due to Mycobacterium malmoense in a child: case report and differential diagnosis of cervical lymphadenitis and lymphadenopathies]. AB - Cervical lymphadenitis and lymphadenopathy are common in children and may be caused by local or systemic infection. There are a large number of possible etiologies. We report the case of a five-year-old boy with unilateral cervical lymphadenitis who was in good health and showed neither clinical nor laboratory signs of systemic infection. Despite repetitive empirical antimicrobial treatment, the lymph nodes increased in size. After surgical excision Mycobacterium malmoense grew from the lymph node culture. Based on a literature search (Embase and Medline 1980-1992), the most frequent infectious etiologies of pediatric cervical lymphadenitis and lymphadenopathies are summarized. Nontuberculous mycobacterial lymphadenitis is most frequent in children between one and five years of age, and is more common in girls than boys. The treatment of choice is surgical excision. In immunocompetent children treatment with antimycobacterial drugs is not needed even if relapse occurs. PMID- 8211028 TI - [50 years of Swiss Academy of Medical Sciences]. AB - The Swiss Academy of Medical Sciences is a foundation under private law, which was founded September 24, 1943, by the Medical and Veterinary Faculties of the Swiss universities and the Swiss Medical Association. It devotes its resources to the advancement of the medical sciences and awards research grants, scholarships and scientific prizes. Its other services include a scientific documentation service (DOKDI), the medical-ethical evaluation of research projects and the publication of guidelines and recommendations for physicians, particularly concerning ethical standards of behaviour. The 50 years' existence of the institution will be commemorated at a ceremony to be held in Berne September 23, 1993. PMID- 8211029 TI - [Therapy of acute salicylate poisoning]. AB - Poisoning with salicylic acid and its derivatives is a quite common event, leading to possibly life-threatening complications. A case of fatal intoxication of a sixty-year old patient with acetylsalicylic acid is described and the therapeutic options are discussed. In acute poisoning it is mandatory to initiate simple and effective measures first. This gives time for discussing and planning the more laborious procedures. The initial treatment of salicylate poisoning is based on the prevention of further absorption by a sufficiently large quantity of orally administered activated charcoal (approximately 1 g/kg b.w.). Given repeatedly, activated charcoal may enhance non-renal clearance of salicylates. Intravenously administered sodium bicarbonate counteracts the metabolic acidosis. Moreover, bicarbonate therapy limits tissue distribution of the drug and enhances its renal excretion. The availability of glycine for salicylic acid metabolism may be limited in poisoning because glycine has been used for forming the conjugation product salicyluric acid. Glycine may be administered orally to overcome this bottleneck. Gastric lavage has been proven to be of limited efficacy. This efficacy is further diminished if gastric lavage is performed late after drug ingestion. When it is performed, however, activated charcoal should be administered before and after gastric lavage. Whenever the more simple treatment options fail, hemodialysis or hemoperfusion should be additionally considered since these procedures are effective in removing salicylates from the body. PMID- 8211030 TI - [Local therapeutic fibrinolysis in ischemic cerebrovascular insults: initial findings in 6 patients]. AB - Local therapeutic fibrinolysis is considered an efficient and established treatment for peripheral arterial occlusive disease. The introduction of newer fibrinolytics along with the development of interventional catheterization techniques have extended its use to previously untreated events such as cerebrovascular occlusions. Between 1989-1991 six patients with basilar and/or middle cerebral artery thrombosis were treated at the University Hospital, Basel, by superselective local intraarterial infusion of 400,000 U/h urokinase for 1-2 hours. Two of four patients with basilar artery occlusion showed complete remission one year after the intervention. The third showed no neurological improvement despite angiographic recanalization, and 48 h later suffered a fatal brainstem haemorrhage, while the fourth did not recover from coma and succumbed. Both patients with occlusion of the middle cerebral artery showed complete recanalization, but one had complete and the other partial neurological remission. Signs of slight systemic fibrinolysis were present but never attained the intensity of systemic therapeutic fibrinolysis as the antiplasmin and fibrinogen values showed. In summary, local therapeutic fibrinolysis contributes to the reduction of mortality and to remission of symptoms in occlusions of basilar artery, and offers some advantage in occlusions of the middle cerebral artery. A definite benefit from the latter will be proved only through large scale randomized trials. The indication for local therapeutic fibrinolysis for thromboses of cerebral arteries requires a careful benefit-risk evaluation, an experienced angiography team and a special infrastructure for computed tomography and digital subtraction angiography. PMID- 8211031 TI - [Screening for alcoholism among patients of a medical polyclinic in French speaking Switzerland]. AB - In order to test an alcoholism screening strategy in a primary care population of a polyclinic, we administered two standardized questionnaires, the Michigan Alcoholism Screening Test (MAST) and the Cut-down, Annoyed, Guilty, Eye-opener Test (CAGE), to all consecutive patients seen during a week. The applicability rate was 77% (269/350). Reasons for being inapplicable were inability to understand the test questions or restricted time allowed for each visit. Tests were positive in 19 and 22%, for the MAST and CAGE, respectively. Kappa coefficient of agreement between tests was 0.69. Based on a positive MAST (cutoff > or = 5), alcoholism was more frequent in males than in females (27 vs 10%), in patients aged 40-49 years (males 45%, females 29%), in unemployed than in employed people (32 vs 22%), in native citizens than in foreigners (21 vs 17%). 23% of MAST positive patients had one or more alcohol-related somatic diseases. Only 60% of MAST positive patients were known to physicians as alcoholics or alcohol-abusers. In conclusion, we showed that (1) prevalence of alcoholism is high in this primary care population, (2) agreement between MAST and CAGE is good, and (3) alcoholism screening is better performed by standardized questionnaires than the usual clinical investigations. PMID- 8211032 TI - [Bacterial infections following sclerosing therapy for esophageal varices]. AB - Two patients with infectious complications 3 and 5 days after elective sclerotherapy of esophageal varices are presented. Both patients had liver cirrhosis (primary biliary cirrhosis and alcoholic liver cirrhosis with hepatitis B virus infection respectively). In one patient a brain abscess developed which was treated successfully by antibiotics and surgery; in the other patient pneumococcal bacteremia and gonarthritis developed. Frequency, possible causes and antibiotic prophylaxis are discussed. PMID- 8211033 TI - [Diagnosis and therapy of endobronchial and tracheal hamartomas]. AB - Endobronchial hamartomas are a tenth as frequent as the usually asymptomatic intrapulmonary hamartomas. We report on 7 patients. 2 men and 3 women had an endobronchial hamartoma. In one patient multiple endobronchial hamartomas were found in the left upper lobe. In a 56-year-old patient with an 8-year history of shortness of breath, cough and several episodes of pneumonia and acute onset of respiratory failure, a tracheal hamartoma was diagnosed. Frequently, endobronchial hamartomas can be resected without loss of lung tissue. Laser resection is often possible and may be the treatment of choice in elderly or inoperable patients. Because of lower risk, laser resection is frequently preferred to conventional operative resection in patients with tracheal hamartomas. PMID- 8211034 TI - [Role of heart transplantation in the treatment of complex congenital malformations in adolescents and adults]. AB - The number of pediatric heart transplants for complex congenital heart disease has increased in recent years, but little experience has been reported in the adolescent and adult population. Between 1987 and 1992, 6 patients (mean age 24 years, range 14 to 42) underwent transplant in our institution because of structural congenital heart disease with or without prior palliative operation or definitive repair. The diagnose covered: congenitally corrected transposition of the great vessels, late systemic ventricular failure after surgically corrected transposition of the great arteries, left superior vena cava, and tricuspid atresia with right ventricular hypoplasia. The palliative repairs included modified Blalock-Taussig shunt, cavo-pulmonary Glenn shunt, two aorto-pulmonary Waterstone shunts, two Blalock-Hanlon atrioseptectomies and one pulmonary valvotomy by the method of Brock. One patient had undergone pulmonary artery banding, in two patients atrial repair by Senning's technique had been performed for definitive repair of transposition of the great arteries. Donor cardiectomy was modified to remove complete inflow and outflow tissue and transplantation was performed without prosthetic material in all patients, in no case was deep hypothermic arrest necessary. There was no early or late mortality after a mean follow-up of 28 months. Postoperative echocardiography and cardiac catheterization demonstrated perfect anatomical and functional results. There was no early or late mortality after a mean follow-up of 28 months. Postoperative echocardiography and cardiac catheterization demonstrated perfect anatomical and functional results. Adult patients with complex congenital cardiac diseases can be transplanted with a very low perioperative risk, even after several prior operative procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8211035 TI - [Subcortical cerebrovascular accidents: correlation between clinical aspects, topography and flow measurements using single photon emission tomography]. AB - 35 patients with subcortical ischemic or hemorrhagic stroke included in the Lausanne Stroke Registry underwent cerebral blood flow measurement using I-123 IMP and 99mTc-HMPAO single photon emission tomography (SPECT). Our findings suggest that neuropsychological disturbances are not systematically correlated to cortical hypoperfusion secondary to the deep lesion (diaschisis). The role of cortical diaschisis was especially prominent in patients with aphasia and left subcortical lesion. PMID- 8211036 TI - [C-reactive protein and early diagnosis of kidney transplant rejection]. AB - C-reactive protein (CRP), which is known to rise rapidly in the serum after tissue injuries or inflammation, was measured daily after renal transplantation during hospitalization up to day 28 in 45 consecutive patients. In 16 patients who developed neither an infection nor rejection the CRP level normalized within 3 to 5 days. In 7 out of 14 patients with graft rejection the CRP level rose 1 to 3 days before the clinical signs of rejection. 11 patients with overt infection all had a CRP rise. 6 other patients had a CRP rise: in 5 the clinical situation explained this rise but in the sixth no explanation was found. We conclude from our results that periodic measurement of CRP (for example twice a week), even under aggressive immunosuppression, can help in the early diagnosis of graft rejection after renal transplantation. In the event of infection CRP loses its usefulness with respect to graft rejection and the daily measurements have no further point. PMID- 8211037 TI - [Periodic hypokalemic paralysis in thyrotoxicosis]. AB - The case is reported of a 26-year-old Chinese cook hospitalized for hypokalemic paralysis, the cause of which was found to be thyrotoxicosis. In Asian males hypokalemic periodic paralysis occurs in 2% to 10% of thyrotoxic patients with a male:female ratio of close to 70:1. In the white population the frequency is smaller by a factor of 10. This association is however considered important, since the clinical symptoms of thyrotoxicosis may be scanty. By successful treatment of thyrotoxicosis hypokalemic paralysis disappears, but may return after cessation of treatment. Pathogenetically, hyperreactivity of the sodium/potassium pump of the cell membrane seems to play an important role. PMID- 8211038 TI - [Diagnosis and therapy of community-acquired pneumonia]. AB - Whereas the diagnosis of community-acquired pneumonia usually is straightforward, in many cases the exact etiology is difficult or impossible to determine. The clinician must have a management strategy for this illness which is not dependent upon precise microbiological diagnosis in each case. Therefore, understanding of the spectrum of community-acquired pneumonias and awareness of the possible pathogens in specific clinical settings is crucial for the choice of the most appropriate antimicrobial therapy. The factors influencing prognosis of community acquired pneumonia are important for the decision as to which patients should be hospitalized. PMID- 8211039 TI - [Quadriceps myopathy as dystrophin-associated myopathy]. AB - Duchenne and Becker muscular dystrophy are both caused by a deletion in the dystrophin gene. In the past few years, many reports of atypical myopathies have been published where an association with a deletion within the same gene was found. We report one sporadic and one familial case of myopathy where we were able to demonstrate a deletion of the dystrophin locus using DNA analysis. PMID- 8211040 TI - [Childhood treatment of paroxysmal supraventricular tachycardia using i.v. adenosine]. AB - Paroxysmal supraventricular tachycardia is the most frequent significant arrhythmia in the pediatric age group, especially in the first year of life. In neonates and infants there are important limitations for the commonly used drugs such as verapamil and digitalis. In an open Swiss multicentre study we treated 19 children with a total of 29 episodes of tachycardia by means of adenosine i.v. as the drug of first choice. 76% of all the tachycardias were converted, whereas the success rate was 87% if only tachycardias with atrioventricular reentry were considered. The important advantage of adenosine lies in its very short half-life of about 15 seconds, which means that the rare relevant, and the more common mild, side effects are quite limited in duration. A major disadvantage are recurrences in about one third of cases. We conclude that adenosine is an efficient and safe treatment for paroxysmal supraventricular tachycardia in the whole pediatric age group including neonates and infants. PMID- 8211041 TI - [Hemorrheology and quality of life in fibrinogen- and lipid-lowering therapy]. AB - Previous studies have demonstrated that heparin-induced extracorporeal LDL precipitation is able to reduce total cholesterol, LDL, triglycerides and plasma fibrinogen at the same time and thus improve the hemorheologic pattern. A combination of H.E.L.P. and bezafibrate, which also has a lipid- and fibrinogen lowering potency, was applied in patients suffering from cerebral multi-infarct dementia and disturbances of the hemorheologic situation. In view of observations regarding improved quality of life after H.E.L.P., a prospective, randomized trial was conducted to determine possible interactions between improved hemorheology and better quality of life. To obtain a low baseline of laboratory parameters, all the patients underwent a single H.E.L.P. session and were then (double-blind) stratified into 2 groups: group 1 (16 males, 5 females, age 67.9 +/- 6.8 years) received sustained-release bezafibrate 400 mg (Bezalip) per day, while group 2 served as controls, and comprised 14 males and 5 females (age 69.2 +/- 6.8 years) who received placebo for a period of 56 days. After H.E.L.P. a statistically significant reduction of the following parameters relevant to hemorheology was obtained: fibrinogen (p < 0.0001), whole blood viscosity (low shear rate p < 0.007 and high shear rate p < 0.005), plasma viscosity (p < 0.002) and red cell transit time (p < 0.0001). Also, the metabolic parameters were influenced positively (p < 0.0001 for total cholesterol, LDL and triglycerides).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8211042 TI - [Health survey of 15-20-year-old adolescents in French-speaking Switzerland]. AB - During the year 1992, under the auspices of the Federal Office for Public Health, the Institute for Social and Preventive Medicine of Lausanne conducted a survey on the health and life-style of a representative sample of adolescents aged 15 to 20 years from the French speaking part of Switzerland. The main objective of the study was to explore adolescent health attitudes and behavior as well as health needs. After exclusion of non valid questionnaires (1.2%), 3324 subjects have been included in the analysis (females: 1477; males: 1847; apprentices: 59%; students: 41%). The majority of the respondents feel in good health (females: 87.5%; males: 94.3%), but a large proportion express needs in various areas: stress, depression, love, professional future, nutrition etc. Comparisons with earlier surveys show that cannabis use has become more common (lifetime prevalence: females: 24.1%; males: 39.3%). The use of hard drugs such as cocaine and heroin is not exceptional (lifetime prevalence: 1-3%). By 18 years of age, the majority of respondents are sexually active (17 years: 49.0%; 18 years: 62.6%; 19 years: 72.0%). 76.6% of respondents have used contraception on their first coitus and thereafter. Girls exhibit a tendency towards more perceived health problems and more use of health care structures, whereas boys express their problems in a more "external" way, i.e. violent behavior (injuries, fighting, theft etc.). Differences between apprentices and students are minimal, although apprentices tend to be more sexually active. The paper comments on the results in different areas such as health care, prevention and general setting. PMID- 8211044 TI - [Annual Joint Meeting of the Swiss Society of Intensive Medicine and the Swiss Society of Pneumology. Lugano, 7-9 October 1993. Abstracts]. PMID- 8211043 TI - [Giant cell arteritis and aortic dissection in 2 siblings]. AB - We present the case of two female siblings with temporal arteritis, polymyalgia and type B aortic dissection. Aortic aneurysms in families are well known in Marfan's and Ehlers-Danlos syndrome; they can, however, occur without signs of a collagen disorder. In patients with arteritis temporalis the incidence of aortic aneurysms is higher than normal. In a retrospective survey of 20,591 autopsies there were 443 aortic aneurysms (2%), 30 (7%) being a consequence of arteritis. Arteritic processes caused 15% of the thoracic and 5% of the abdominal aneurysms. This is the first description of temporal arteritis, polymyalgia and aortic dissection in siblings. The observation illustrates the danger of aneurysmatic aortic dilatation and/or dissection at a later or chronic stage of arteritis. PMID- 8211045 TI - [Assessment of gastric emptying]. AB - In the absence of overt mucosal lesions, abnormalities of gastroduodenal motorfunction are considered to be important in the pathogenesis of many upper abdominal symptoms. These may be idiopathic, occur following gastric surgery, or in association with diseases such as diabetes mellitus. A variety of investigations have been developed to examine the motility of the stomach and duodenum. To date the most reliable and useful techniques are those which assess gastric transit either radiologically or scintigraphically. Assessment of the expulsion of radio-opaque gastric markers with a single abdominal x-ray can be performed as a simple outpatient screening procedure. More precise radioisotopic definition of delayed gastric emptying, however, requires access to a Nuclear Medicine Department. A number of other approaches are currently under investigation as potential diagnostic tests. The future role of these techniques is unclear, although 13C breath testing may soon permit rapid and simple screening of gastric emptying abnormalities without exposure to ionizing radiation. At present, other techniques such as ultrasound, antropyloroduodenal manometry, and magnetic resonance imaging have application only in research centers. PMID- 8211046 TI - [Gallbladder dyskinesia and manometry of Oddi's sphincter]. AB - Sphincter of Oddi activity partly regulates bile flow into the small intestine. This regulation is mainly controlled by phasic contractions and basal tone of the sphincter, together with gallbladder contraction. Manometric studies of the sphincter have permitted a better understanding of its physiological role and implication in biliary dyskinesia symptoms. Motility abnormalities of Oddi's sphincter present classically as bouts of recurrent pain and/or idiopathic pancreatitis, that can be successfully cured by endoscopic sphincterotomy. PMID- 8211047 TI - [Evaluation of small intestinal motility]. AB - Disturbances of small bowel motor function are increasingly recognized in clinical practice, either in the setting of an underlying disease that may affect the neuro-hormonal control of gut motility, such as diabetes or scleroderma, or as part of unexplained intestinal dysfunctions such as the irritable bowel syndrome or chronic idiopathic intestinal pseudo-obstruction. In the absence of endoscopic or radiological mucosal disease, it is often clinically helpful to define the motor function of the small bowel to understand the origin of the patient's symptoms. The hydrogen breath test after a lactulose oral load is currently used to measure mouth to caecum transit time. However, the reproducibility of this test is poor, and the range of normal values is wide. Scintigraphic determination of small intestinal transit time overcomes some of the limitations of the hydrogen breath test. This is however a time consuming procedure--up to 10 hrs when the time for acquisition, processing and analysis is included--and the costs prohibit widespread application of the technique. It is further restricted by the exposure to ionising radiation, particularly if repeated evaluations are necessary, for example in drugs trials. Manometry records mechanical activity of the bowel and detects quantitative and qualitative changes of small intestinal motility. As with scintigraphy, high costs and radiation exposure limit its usefulness. The major clinical application of the technique is in the diagnosis of chronic intestinal pseudo-obstruction. PMID- 8211048 TI - [Colonic motility]. AB - Colonic motility is provided by contraction of intramural smooth muscle under the control of the enteric and the extrinsic nervous system and humoral connections. In vivo measurement of colonic motility remains difficult because of the complexity of these interactions and anatomical considerations. The possibility that symptoms are due to colonic dysmotility should be considered in patients with normal barium enema and colonoscopy. Examples of this are patients with chronic constipation, irritable bowel syndrome or colonic symptoms associated with diabetes mellitus or diseases of the nervous system. A number of techniques have been developed to assess colonic motility. The simplest is to assess colonic transient with a single abdominal x-ray following ingestion of radio-opaque markers. This is cheap, reproducible and easy to perform. Normal values for age and sex are available. Colonic transit of both liquid and solid can be determined by scintigraphic measurement. This technique provides information about regional variations in colonic function; it is however relatively demanding and requires access to a gamma camera. Manometry provides a more direct assessment of colonic motor activity. Changes in the electrical potential of the colonic smooth muscle can be determined by electromyography. Both techniques are however difficult to perform, and are currently only used for research purposes. It is likely that the combination of techniques that examine transit with more direct measurement of motor function will provide further insights into the mechanisms responsible for colonic dysmotility. PMID- 8211049 TI - [Evaluation of anorectal motility]. AB - Constipation and incontinence frequently lead to medical consultation. A careful history and a complete physical examination of both anus and rectum are required before performing anorectal motility tests, the most important of which are anorectal manometry coupled with electromyography of the external anal sphincter and defecography. The pathophysiologic origin of these symptoms can then be understood. This has led to the development of new therapies such as bio-feedback or corrective surgery. PMID- 8211050 TI - [Drugs and assessment of gastrointestinal motility]. AB - Any determination of gastrointestinal motility is based on two assumptions: (1) That the patient is examined in "physiological" conditions and (2) that the values measured truly reflect the parameter the investigator wishes to examine. A large array of very different drugs shares the ability to modify the digestive motility (i.e. gastrokinetics) or to alter the content of the digestive tube in such a way that it affects the outcome of some measurements (i.e. acid suppression leads to false results in ph-metry dependent methods). Therefore, it seems advisable to ask the patient whether he is taking any drug--including non prescription medications--and check if this substance or type of substances could affect the outcome of the motility measurement envisioned. In this paper, the authors present a list of the principal drugs known to affect different motility measurement methods. The real or apparent stimulating or inhibitory effects of drugs on four main segments of the digestive tube (esophagus, stomach, small intestines and colon) are indicated in an alphabetically ordered table. In a short review, the drugs are broadly classified according to their mechanism and site of action. Besides a number of drugs used in practice because of their action on the enteric nervous system, there is a large spectrum of compounds affecting motility, whose main therapeutic application lies outside the digestive tract, such as: psychotropic drugs, antiparkinsonian drugs, bronchodilators, antitussives, antihistamines, antimigraine drugs, antihypertensive agents, etc. This second category is more likely to escape unnoticed as a potential source of false results in the measurement of digestive motility. PMID- 8211051 TI - [Gastrointestinal motility]. PMID- 8211052 TI - [Motility disorders and assessment methods of the esophagus]. AB - Esophageal diseases frequently cause symptoms such as heartburn, epigastric pain and dysphagia. This article discusses the indications, techniques and limitations of currently available diagnostic procedures. Investigation of symptoms should proceed in a logical stepwise manner, beginning with endoscopy to exclude esophagitis or neoplasia. Symptoms due to acid reflux can be identified by 24h esophageal pH-metry to document a temporal association between symptoms and episodes of esophageal acidification. Stationary or ambulatory manometric recording of esophageal pressures can be used to diagnose esophageal motor disorders such as achalasia, nutcracker esophagus, diffuse esophageal spasm, or dysfunction of the upper or lower esophageal sphincter. Combined 24 h pH manometry should be used to test the temporal association between pain, reflux, or abnormal motility in patients with non-cardiac chest pain. Video-fluoroscopy is the most appropriate technique to diagnose swallowing disorders. Pulmonary aspiration of gastro-esophageal reflux can be documented with scintigraphy. PMID- 8211053 TI - [Homeopathy: a field of work for the veterinarian]. AB - It is generally known that Homeopathy and other so-called alternative methods of treatment have recently been gaining acceptance. The profession of lay animal practitioner is no longer a rarity in Switzerland. For some, alternative medicine is one phenomenon among others in a saturated health market and thrives on the fact that classical medicine does not yet extend to all areas. For others, the search for alternatives corresponds to a justified demand by the practitioners and denotes an extension of the medical disciplines. The Workshop for Veterinary Acupuncture and Homeopathy (AGVAH) was founded several years ago by veterinarians in Switzerland. It represents the professional interests of its members and upholds their right to practice these forms of therapy. The ensuing debate between classical and alternative medicine questions not only the basis of Homeopathy and similar forms of medicine, but also that of scientific thought. The realization that any scientific approach has its limits can open a door to deeper understanding of traditional occidental medicine. PMID- 8211054 TI - [Demonstration of a ventricular septum defect in a dog by color Doppler echocardiography, angiocardiography and selective oximetry]. AB - A ventricular septum defect in a dog has been diagnosed by angiocardiography and color-doppler-echocardiography. The results were compared with those obtained by invasive oxymetry and pressure measurements. PMID- 8211055 TI - [The glandular compartments of the canine placenta--a scanning electron microscopic study]. AB - The glandular chambers in the spongy zone grow out of the superficial endometrial glands during the implantation of the embryo. To our knowledge, no scanning electron microscopic investigations of the spongy layer in the placenta of the bitch have been published so far. We examined the placenta at the 44. day of pregnancy by scanning electron microscopy. The glandular epithelium in the spongy zone forms extensive folds, which fill up most of the lumen of the glandular chambers. They are lined by a simple columnar epithelium with high apical protrusions. The luminal surface of the cells is bordered by short microvilli. Numerous vesicles are stacked in the cytoplasm. The tips of the chorionic tufts project into the lumen of the glandular chambers. The lumen is filled with masses of mucus separating the trophoblast from the glandular epithelium. With respect to its morphology, the trophoblast lining the tips of the chorionic tufts is very different from the trophoblast in the other parts of the placenta. The cells are swollen and club-shaped. The cytoplasm is completely supplanted by big vacuoles. We feel that the trophoblast in the glandular chambers is unable to perform any resorptive activity. The significance of the mucus in the glandular chambers in stopping the invasive growth of the trophoblast is discussed. PMID- 8211056 TI - [Serologic monitoring of pullet and laying hen flocks in Switzerland: results from the years 1990 and 1991]. AB - In 1990 and 1991 4522 blood samples from 398 pullet flocks and 1338 blood samples from 128 laying flocks were monitored for antibody against infectious bronchitis virus, infectious laryngotracheitis virus, adenovirus, reovirus, infectious bursal disease virus, Newcastle disease virus, Mycoplasma gallisepticum and Mycoplasma synoviae. The results are discussed for pullets and laying hens. PMID- 8211057 TI - [Hepatic lipoprotein receptors]. PMID- 8211058 TI - [Advances in the research on interferon alpha/beta receptor and the mechanisms of signal transduction]. PMID- 8211059 TI - [Cytokines modulation of hypothalamo-pituitary-adrenal axis]. PMID- 8211060 TI - [Advances in the research on P34CDC2 kinase]. PMID- 8211061 TI - [Progress in the study of protein kinase C]. PMID- 8211062 TI - [Shock and regulatory peptide]. PMID- 8211063 TI - [Morphological study of the effect of morphine on the plasticity of the spinal cord in rats]. PMID- 8211064 TI - [Advances in the research on anti-oncogenes P53]. PMID- 8211065 TI - [Proto-oncogene c-fos and convulsion]. PMID- 8211066 TI - [Myo D1: an important myogenic transcription regulator]. PMID- 8211067 TI - [Benzodiazepines and gamma-aminobutyric acid A/benzodiazepines/chloride channel receptor complex]. PMID- 8211068 TI - [Regulation of cytosolic calcium in vascular endothelial cells]. PMID- 8211070 TI - [The role of catecholamines and adrenoceptors in cardiac hypertrophy]. PMID- 8211069 TI - [Effects of neuropeptide Y]. PMID- 8211071 TI - [The properties and function of the vacuolar proton-pump]. PMID- 8211072 TI - [Thyrotropin-releasing hormone and gastrointestinal function]. PMID- 8211074 TI - [Natural antioxidants and their anticarcinogenic effect]. PMID- 8211073 TI - [Progress in the study of the distinct luteal cell subpopulations]. PMID- 8211075 TI - [Whole cell recording from neurons in slice preparation of mammalian]. PMID- 8211076 TI - [Relation between cerebral dopaminergic system and pharmacological action of 1 tetrahydroprotoberbines]. PMID- 8211077 TI - [A brief historical retrospect (Zheng Pei-Lieu)]. PMID- 8211078 TI - [I should not have taken part in the race]. PMID- 8211079 TI - [Amphetamine doping in leisure-time mountain climbing at a medium altitude in the Alps]. AB - Although doping in leisure sports may potentially be of relevance for medical emergency situations, it has attracted much less attention than doping in elite athletes. The aim of our study was to evaluate the prevalence of amphetamine consumption in medium altitude mountaineering. Urine samples were taken from 253 males after a successful ascent. Analysis for amphetamines proved positive for 7.1% of mountaineers climbing above 3300 m. On peaks between 2500 to 3300 meters above sea level, 2.7% of the mountaineers we examined had amphetamines residues in their urine. Below 2500 meters, no positive sample was detected. For tourists living outside of the Alpine range, we noticed a significantly higher proportion of positive analyses. We conclude that attempts to induce a higher performance level by pharmacological means are not overly uncommon in leisure mountaineering. Such a behaviour may be of medical relevance in emergency situations. PMID- 8211080 TI - [An analysis of overstrain injuries in rock climbing]. AB - Between spring and autumn 1990 a study was performed with the goal of recording and classifying overstrain injuries due to rock-climbing and to define their causes. Of the 332 climbers participating in the study, 114 (34.4%) had suffered from at least one overstrain injury. The degree of climbing skill proved to be the main risk factor; with increasing climbing skills of the observed persons the percentage of injuries increased very substantially. The degree of climbing skill also was the only significant difference between injured and non-injured persons- injured persons had a climbing skill which was 1.3 degrees (UIAA) higher. Warming up was unable to prevent most overstrain injuries. A total of 237 injuries were described. 34.6% of these were long-term defects such as foot deformations and nail dystrophies of the toes. 65.4% were overstrain injuries; 90.3% of these cases concerned the upper part of the body and the upper extremities including the thoracic girdle, areas which are particularly strained in climbs of high degrees of difficulty. The areas affected were almost exclusively tendons, joint capsules and ligaments. By far the most frequent injury of the upper extremity was the proximal interphalangeal joint injury, followed by injuries to the proximal phalanx, the flexor tendons of the forearm and the distal interphalangeal joint. With regard to training injuries, finger injuries occurred most frequently in addition to elbow injuries. 51% of the overstrain injuries were severe, with healing times of months to years. Only 30% of the injured persons consulted a physician. PMID- 8211081 TI - [The pulmonary manifestations of diving accidents]. AB - Scuba diving is associated with risks of drowning, lung barotrauma and decompression sickness. In case of near-drowning, irreversible neurologic lesions or death may follow an acute hypoxemia or a cardiopulmonary arrest. Therefore, victims of drowning should benefit from an immediate and prolonged cardiopulmonary resuscitation. Lung barotrauma are due to the failure of expanding lung gases to escape during ascent; they are likely to be complicated by arterial gas embolism. They can follow a panic ascent even from a shallow depth. Most of decompression procedures induce the formation of asymptomatic venous gas bubbles, normally filtrated and eliminated by the lungs. In case of massive intravenous bubbling, the filtering capacity of the lungs can be overwhelmed and the lung microcirculation damaged up to the point of provoking a cardio-respiratory failure. PMID- 8211082 TI - [A critical assessment of Trendelenburg's position in the acute phase after a diving accident]. AB - For several years now, a controversy has developed on how to position a patient after a decompression accident with acute gas embolism. The usefulness of the so called Trendelenburg position, based on experimental evidence gathered on dogs, has recently been challenged. The basis assumption was that cerebral embolism may be reduced by the hydrostatic effect of putting the head below the body's center of gravity. This position however required much technical resourcefulness and often delayed the first therapeutic intervention. Newer experimental research shows that, contrary to the old theory, positioning the head below feet level increases the intra-cranial pressure, injuring the blood-brain barrier, even when done under hyperbaric oxygen therapy. A wide consensus has now emerged, which should be communicated to first-aid personnel, so that no more time is being lost in trying to position the accidented diver by unduly complicated means. The current recommendations asks for laying the injured diver horizontally on its back, or sideways, if he is unconscious. It is by far more important to control its vital functions, give first-aid, administer oxygen in closed circuit, and shorten as much as possible transport time to the next center for hyperbaric therapy. PMID- 8211083 TI - The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness in healthy adults. Position stand of the American College of Sports Medicine. AB - The combination of frequency, intensity, and duration of chronic exercise has been found to be effective for producing a training effect. The interaction of these factors provide the overload stimulus. In general, the lower the stimulus the lower the training effect, and the greater the stimulus the greater the effect. As a result of specificity of training and the need for maintaining muscular strength and endurance, and flexibility of the major muscle groups, a well-rounded training program including resistance training and flexibility exercises is recommended. Although age in itself is not a limiting factor to exercise training, a more gradual approach in applying the prescription at older ages seems prudent. It has also been shown that endurance training of fewer than 2 d/wk, at less than 50% of maximum oxygen uptake and for less than 10 min/d, is inadequate for developing and maintaining fitness for healthy adults. In the interpretation of this position statement, it must be recognized that the recommendations should be used in the context of participants' needs, goals, and initial abilities. In this regard, a sliding scale as to the amount of time allotted and intensity of effort should be carefully gauged for both the cardiorespiratory and muscular strength and endurance components of the program. An appropriate warm-up and cool-down, which would include flexibility exercises, is also recommended. The important factor is to design a program for the individual to provide the proper amount of physical activity to attain maximal benefit at the lowest risk. Emphasis should be placed on factors that result in permanent lifestyle change and encourage a lifetime of physical activity. PMID- 8211084 TI - Autoimmune disease. PMID- 8211085 TI - Allergy and the immune system. PMID- 8211086 TI - The immune system as a therapeutic agent. PMID- 8211087 TI - Will we survive? PMID- 8211088 TI - Malignant mimicry. False estrogens may cause cancer and lower sperm counts. PMID- 8211089 TI - Fads and feds. Holistic therapy collides with reductionist science. PMID- 8211090 TI - Life, death and the immune system. PMID- 8211091 TI - Life, death and the immune system. PMID- 8211092 TI - How the immune system develops. PMID- 8211093 TI - How the immune system recognizes invaders. PMID- 8211094 TI - How the immune system recognizes the body. PMID- 8211095 TI - Infectious diseases and the immune system. PMID- 8211096 TI - AIDS and the immune system. PMID- 8211097 TI - [Sonographic pathology of the axilla. Part I]. AB - In comparison with other diagnostic modalities axillary sonography undoubtedly is highly valuable in when examining unclear palpation findings, in the staging of tumours with lymphatic drainage to the axilla and in post-therapeutic screening of cancer patients. Usually pathologic changes of the axilla are due to diseases of the lymph nodes. Infrequently there are soft tissue tumours, inflammations, diffuse changes of the axillary soft tissue, vascular diseases and pathologic findings of the shoulder joint. Provided the most common sonographic features of morphologic changes of the axillary tissues are known, sonography of the axilla is a very important diagnostic tool and is extremely helpful in deciding on further diagnostic and therapeutic procedures. Part I deals with the pathology of the axillary lymph nodes, whereas in part II pathological changes of the other soft tissues are discussed in detail. PMID- 8211098 TI - [Sonographic findings in the hip of newborn infants after pregnancy and labor from breech position]. AB - In the period between October 1990 and July 1992 58 newborn were ultrasonographically examined because of intrauterine breech presentation and therefore higher pressure on the fetal hips. These children were compared with other 66 children who had neither risk factors nor family disposition. We noted significant differences in the distribution of hip dislocation types (by Graf) between both groups. There was a normal distribution among the control group. Children in breech presentation, whether twin or single pregnancy, showed the following: (1) shift of the fine distribution to type Ia, (2) increase of type IIa, classified as pathological not before the 3rd month of life (type IIb, persistence of delay of ossification), (3) two hip dislocations type IIg, (4) one hip dislocation type IIIa. We recommend to perform ultrasound screening after delivery in all children who have had an intrauterine breech presentation, so that treatment can be started as soon as possible. PMID- 8211099 TI - [Diagnostic value of continuous wave (cw) Doppler sonography in maternal diabetes mellitus]. AB - Doppler studies of umbilical, uterine and arcuate artery velocity wave forms were performed in 40 insulin-dependent diabetic women in the first and second half of pregnancy. Using a continuous-wave Doppler device, the resistance index (RI) was calculated to determine the degree of vascular resistance in utero-placental and foeto-placental compartment. The 90th percentile was used to classify flow velocity profiles. In addition, diastolic notching and incomplete registration of uterine and arcuate arteries were considered as an abnormal result in utero placental perfusion. The prevalence of abnormal velocity wave forms in this risk group was higher than in a non-diabetic population. No significant correlation was found between abnormal Doppler studies and White's classification. Patients with vasculopathy represent a high-risk group for foetal growth retardation, which may be detected early by umbilical and especially uterine artery Doppler studies. Abnormal uterine and arcuate artery wave forms allowed identification of patients who developed pregnancy-induced hypertension/preeclampsia. PMID- 8211100 TI - [Doppler flow measurements of the uterine artery. A prognostic factor for success in treatment by IVF?]. AB - 117 patients treated for infertility with IVF-ET were included in a prospective study to evaluate the prognostic value of Doppler-flow measurements in the uterine artery on the day of oocyte retrieval. The PI was calculated after transabdominal pulsed Duplex-Doppler-flow measurement in the uterine artery, which was localised in the B-scan or using a colour Doppler. The success of the IVF procedure could be predicted statistically significant for both--pregnant or not--(p = 0.0316) and--ongoing pregnancy or first trimester abortion--(p = 0.0079) by better uterine flow. At the same time the diameter of the endometrium was measured. There is only a statistical trend for better results in cases with larger endometrial diameter comparing pregnant and non-pregnant patients (p = 0.0708). The results suggest that the uterine flow measurements might be helpful in selecting cycles for successful embryo transfer. PMID- 8211101 TI - [Prenatal diagnosis of fetal teratomas]. AB - Teratomas are the most frequent tumours in a newborn child. Prenatal ultrasound allows an early diagnosis with high significance. Six cases are described by prenatal sonographic signs, clinical management and pathologic-anatomic findings. Since teratomas are mostly benign and surgery is often successful, sufficient cooperation between obstetricians, surgeons and neonatologists is important. PMID- 8211102 TI - [Prenatal diagnosis of type II Arnold Chiari malformation]. AB - During a 7-year-period 22 foetuses with an Arnold-Chiari deformity were diagnosed. The reason for referring to our centre were severe additional malformations. In 2 cases protrusion of the fetal brainstem is documented by sonography prenatally. Prenatal diagnosis of an ACM has not been documented in the literature. The cytogenetic and microbiological findings including the additional malformations are presented. Pathogenesis, outcome and treatment options are discussed. PMID- 8211103 TI - Immunochemical analysis of water micropollution. AB - Immunoassays for detecting and measuring organic microcontaminants in water supplies are gaining acceptance and are becoming more widely available. A number of assays for pesticides have been described. Immunoassays especially those utilising enzyme labels are ideally suited for rapid and low cost monitoring of water quality. One of the major attractions of immunoassays for water analyses is the sensitivity that can be achieved without sample preparation. Limits of detection below the EC Maximum Admissible Concentration (0.1 microgram/l) are regularly obtained with acceptable assay performance in terms of accuracy and precision. The selectivity of analysis depends on the specificity of the antibody used. Generally antisera are compound or group specific and unlike conventional analyses only one analyte can be measured at one time. Enhanced luminescence has provided an alternative sensitive and robust endpoint for immunoassays of herbicides and can be adapted to produce semiquantitative results away from the laboratory. PMID- 8211104 TI - Transport of radiocaesium from a sheep's diet to its tissues. AB - Transfer coefficients for radiocaesium transport from a sheep's diet to blood, muscle, lung, liver, kidney, spleen heart, brain, rumen, intestines and fat were measured in a controlled experiment involving 50 adult ewes. The animals were fed dry grass and wheat, both contaminated with Chernobyl fallout debris, for a period of 60 days. During this period half of the animals were killed at regular intervals and samples of their blood and tissues were measured for radiocaesium concentration. The rest of the animals were returned to uncontaminated food and were monitored for radiocaesium concentration through periodic slaughtering for an additional 60 days. Transfer coefficients were extracted from the plateau reached at the end of the contamination phase. The data were also analyzed by means of a recently proposed linear multiple compartment model and transport rate parameters for each compartment were extracted. Transfer coefficients computed through the model's transport rate parameters show remarkable agreement with the experimentally obtained values. PMID- 8211105 TI - Aquatic genotoxicity testing with rat hepatocytes in primary culture. I. SCE induction. AB - Primary cultures of adult rat hepatocytes were tested for their suitability to assess the genotoxic potential of effluent water samples by means of sister chromatid exchange induction. The results obtained with a variety of industrial effluents indicate a high sensitivity of this system since significantly elevated levels of SCE could be demonstrated in the undiluted sample and dilutions down to concentrations of 0.01%. However, the results also showed that the sole examination of an undiluted sample can lead to misinterpretations due to the shape of the dose response curves; in the worst case no genotoxic effect will be found although the sample has both toxic and genotoxic activity. Therefore, to assess the potential genotoxicity, it will be necessary to determine SCE induction with several dilutions of the effluents under investigation. PMID- 8211107 TI - Low lead level in teeth in Israel. AB - A total of 180 sound teeth extracted from people living mainly in Northern Israel and some in the center of the country, aged 14-75 years, were analysed by graphite furnace atomic absorption spectrophotometer. The average lead level in teeth roots ranged between 1.61-25.72 micrograms/g dry root, according to the donor's age. This low level was measured in all the regions which were checked, with no significant differences between them, despite differences in levels of motor traffic rates. Based on the low lead level in teeth, we assume that no further reduction in the lead level in gasoline is needed, as long as motorization rate or gasoline consumption does not change significantly. PMID- 8211106 TI - Radiocaesium transfer to sheep's milk as a result of soil ingestion. AB - Soil ingestion as a source of radiocaesium contamination to ruminants was studied by measuring the transfer coefficient to sheep milk. Eight lactating ewes, housed in individual metabolism cages, were used. Fifty grams per day of heavily contaminated sandy topsoil, collected in 1990 from the Chernobyl area, were administered orally to the animals for a period of 1 week. The daily dose intake in 137Cs was 1835 Bq day-1. During this contamination period, daily milk production and excreta output were measured. The ewes were monitored for an additional 7 day decontamination period, while they fed on uncontaminated feed. Transfer coefficients were obtained through a best fit (minimum chi 2) of the data to predictions of a linear compartment model. The values obtained were fm = (2.6 +/- 0.7) x 10(-2) and f mu = (5 +/- 2) x 10(-2) days kg-1 for radiocaesium transport to milk and urine, respectively. These results suggest that soil ingestion can be a major source of radiocontamination for sheep and other free grazing ruminants. Comparison of our results with soil-to-milk transfer coefficient values derived in two recent independent experiments suggests that there might be a strong dependence of radiocaesium availability on soil composition. PMID- 8211108 TI - Some toxic and essential trace metals in cattle from the northern part of Poland. AB - The concentrations of mercury, cadmium, lead, copper, manganese, zinc and iron have been determined in muscle (meat), liver and kidney of cattle slaughtered in the northern part of Poland between 1987 and 1991. The method of measurement was cold vapour flameless AAS for mercury and flame AAS for other metals. The arithmetic mean weighted concentrations obtained related to wet-weight for muscles, liver and kidneys of cattle were 1.2, 4.2 and 11 micrograms kg-1 for mercury; 6, 120 and 610 micrograms kg-1 for cadmium; 40, 160 and 210 micrograms kg-1 for lead; 1.2, 29 and 5.6 mg kg-1 for copper; 0.11, 1.8 and 0.93 mg kg-1 for manganese; 34, 43 and 22 mg kg-1 for zinc and 23, 44 and 72 mg kg-1 for iron, respectively. No clear trends with time of toxic trace metals have been found in bovine muscle and edible organs during the period studied. The results obtained are reviewed and discussed with the data reported for muscle, liver and kidneys of cattle in Poland from other studies. PMID- 8211109 TI - Some toxic and essential trace metals in swine from northern Poland. AB - The concentrations of mercury, cadmium, lead, copper, manganese, zinc and iron have been determined in muscle (meat), liver and kidneys of swine slaughtered in the northern part of Poland between 1987 and 1991. The method of measurement was cold vapour flameless AAS for mercury and flame AAS for other trace metals. The concentrations of such toxic metals as mercury, lead and cadmium were relatively low or very low. The arithmetic mean weighted concentrations obtained related to fresh weight for muscle, liver and kidneys of swine were 1.9, 3.7 and 7.0 micrograms kg-1 for mercury, 5, 41 and 240 micrograms kg-1 for cadmium, 20, 94 and 120 micrograms kg-1 for lead, 1.1, 8.5 and 8.4 mg kg-1 for copper, 0.11, 1.3 and 1.3 mg kg-1 for manganese, 26, 50 and 30 mg kg-1 for zinc and 13, 54 and 63 mg kg-1 for iron, respectively. No definite time trends of mercury, cadmium and lead concentrations in swine muscle and edible organ meats during the period studied were observed, while for an essential trace metals analysed the values obtained seem to be typical. The results noted are reviewed and discussed with the data reported for muscle, liver and kidneys of swine in Poland from other studies. PMID- 8211110 TI - Effect of the reduction of petrol lead on the blood lead levels of South Africans. AB - Lead has no metabolic role in the human body and its presence is associated with various toxic effects. Several countries have responded to this health hazard reducing petrol lead additives or entirely eliminating them. Studies have shown that there has been a resultant fall in blood lead levels of the particular populations. This study reports on the progressive decline in blood lead levels of South Africans during the period 1984-1990 which coincided with a stepwise reduction in petrol lead additives from 0.8 g/l to 0.4 g/l. During this period the blood lead levels of Cape Town city dwellers decreased significantly (P < 0.01) from 9.7 micrograms/dl to 7.2 micrograms/dl. This blood lead level compares favourably with that of other more industrialized countries with less lead in their petrol. Therefore, the authors question the need for further reduction of petrol lead content bearing in mind the considerable financial burden that such a step will entail and the dubious health advantage that may be gained. PMID- 8211111 TI - Daily dietary intake of copper, zinc and selenium by different population groups in Burundi, Africa. AB - Daily dietary intake of copper, zinc and selenium for different population groups in Burundi, Africa, has been determined, using different sampling strategies, by atomic absorption spectrometry. Recommended daily intakes (RDA, National Academy, USA) are met for copper and zinc. For selenium, especially the rural population risk a deficiency as observed with a daily intake of 17 micrograms. The importance of different types of food in daily intake is discussed. Legumes proved to be an important source of copper, while for selenium fish contributes in a large part in dietary intake. Calculated total daily intakes are compared with intakes recently published for other countries. PMID- 8211112 TI - Interaction of mammalian splicing factor SF3a with U2 snRNP and relation of its 60-kD subunit to yeast PRP9. AB - In the assembly of a prespliceosome, U2 small nuclear ribonucleoprotein (snRNP) functions in pre-messenger RNA (mRNA) splicing together with splicing factors (SFs) 3a, SF3b, and several other proteins. The 17S but not the 12S form of U2 snRNP is active in splicing-complex formation. Here it is shown that the SF3a subunits correspond to three of the 17S U2 snRNP-specific polypeptides. SF3a interacts with U2 snRNP in the presence of SF3b to generate a structure similar to 17S U2 snRNP, which suggests a function for SF3a and SF3b in the incorporation of U2 snRNP into the spliceosome. Furthermore, the 60-kilodalton subunit of SF3a is related to the yeast splicing protein PRP9. PMID- 8211113 TI - Correspondence between a mammalian spliceosome component and an essential yeast splicing factor. AB - None of the mammalian splicing factors that have been cloned corresponds to the yeast pre-messenger RNA splicing factors, the PRP proteins. Here, a generalizable strategy was used to isolate a complementary DNA encoding the mammalian spliceosome-associated protein (SAP) SAP 62. It is demonstrated that SAP 62 is the likely functional homolog of the yeast PRP11 protein. Both PRP11 and SAP 62 associate stably with the spliceosome, contain a single zinc finger, and display significant amino acid sequence similarity. Unlike PRP11, SAP 62 contains 22 proline-rich heptapeptide repeats at the carboxyl-terminus. PMID- 8211114 TI - Interaction between PRP11 and SPP91 yeast splicing factors and characterization of a PRP9-PRP11-SPP91 complex. AB - Several proteins are involved in the early steps of the spliceosome assembly pathway. Protein-protein interactions have been identified between two Saccharomyces cerevisiae yeast splicing factors, PRP9 and SPP91. Here it is demonstrated that protein-protein interactions occur between SPP91 and PRP11. The combination of the prp9-1 mutant and a truncated prp11 mutant exhibits a synthetic lethal phenotype, suggestive of a common biochemical defect. The PRP9 and PRP11 proteins do not interact directly, but the PRP9 and PRP11 molecules can simultaneously bind SPP91 to form a three-molecule complex. Structurally and functionally related proteins are found in mammalian cells and are associated in a single biochemical fraction. This strongly suggests that the PRP9-SPP91-PRP11 complex is a key element of the splicing machinery. PMID- 8211115 TI - Pushing at the envelope. PMID- 8211116 TI - Ordered restriction maps of Saccharomyces cerevisiae chromosomes constructed by optical mapping. AB - A light microscope-based technique for rapidly constructing ordered physical maps of chromosomes has been developed. Restriction enzyme digestion of elongated individual DNA molecules (about 0.2 to 1.0 megabases in size) was imaged by fluorescence microscopy after fixation in agarose gel. The size of the resulting individual restriction fragments was determined by relative fluorescence intensity and apparent molecular contour length. Ordered restriction maps were then created from genomic DNA without reliance on cloned or amplified sequences for hybridization or analytical gel electrophoresis. Initial application of optical mapping is described for Saccharomyces cerevisiae chromosomes. PMID- 8211117 TI - Erythrocyte P antigen: cellular receptor for B19 parvovirus. AB - The pathogenic human parvovirus B19 replicates only in erythroid progenitor cells. This virus was shown to bind to blood-group P antigen, as measured by hemagglutination. Erythrocytes lacking P antigen were not agglutinated with B19. Purified P antigen (globoside) blocked the binding of the virus to erythroid cells and the infectivity of the virus in a hematopoietic colony assay. Target cells were protected from infection by preincubation with monoclonal antibody to globoside. Knowledge of a parvovirus receptor has implications for understanding the pathogenesis of parvovirus infections and for the use of parvoviruses in gene therapy. PMID- 8211118 TI - In vivo gene therapy of hemophilia B: sustained partial correction in factor IX deficient dogs. AB - The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo. PMID- 8211119 TI - Biodiversity entreaty. PMID- 8211120 TI - The chlorine controversy. PMID- 8211121 TI - Taking stock of the Genome Project. PMID- 8211122 TI - Scientific misconduct. Michigan gets an expensive lesson. PMID- 8211123 TI - NIH told to reconsider crime meeting. PMID- 8211124 TI - Peer Review goes under the microscope. PMID- 8211125 TI - A first step toward gene therapy for hemophilia B? PMID- 8211126 TI - Cancer therapy. Hope for a magic bullet that moves at the speed of light. PMID- 8211127 TI - A new five-year plan for the U.S. Human Genome Project. PMID- 8211128 TI - Managing all those bytes: the Human Genome Project. PMID- 8211129 TI - Presymptomatic diagnosis: a first step toward genetic health care. PMID- 8211130 TI - A genetic linkage map of the mouse: current applications and future prospects. AB - Technological advances have made possible the development of high-resolution genetic linkage maps for the mouse. These maps in turn offer exciting prospects for understanding mammalian genome evolution through comparative mapping, for developing mouse models of human disease, and for identifying the function of all genes in the organism. PMID- 8211131 TI - Genome maps IV 1993. Wall chart. PMID- 8211132 TI - Protein ladder sequencing. AB - A new approach to protein sequencing is described. It consists of two steps: (i) ladder-generating chemistry, the controlled generation from a polypeptide chain by wet chemistry of a family of sequence-defining peptide fragments, each differing from the next by one amino acid; and (ii) data readout, a one-step readout of the resulting protein sequencing ladder by matrix-assisted laser desorption mass spectrometry. Each amino acid was identified from the mass difference between successive peaks, and the position in the data set defined the sequence of the original peptide chain. This method was used to directly locate a phosphoserine residue in a phosphopeptide. The protein ladder sequencing method lends itself to very high sample throughput at very low per cycle cost. PMID- 8211133 TI - Alloimmunization as an AIDS vaccine? PMID- 8211134 TI - A magic bullet against AIDS? PMID- 8211135 TI - T cell shift: key to AIDS therapy? PMID- 8211136 TI - Mother-infant HIV trial on track. PMID- 8211137 TI - Breathing while trotting. PMID- 8211138 TI - Control of the exo and endo pathways of the Diels-Alder reaction by antibody catalysis. AB - Catalytic antibodies that control the reaction pathways of the Diels-Alder cycloaddition have been generated. One antibody catalyzes the favored endo and the other the disfavored exo pathway to yield the respective cis and trans adducts in enantiomerically pure form. A comparison of the x-ray structure of the hapten with the calculated geometry of the transition structure showed that [2.2.2] bicyclic compounds are excellent mimics of the transition state of the Diels-Alder reaction. To achieve catalysis and the high degree of stereoselectivity shown here, the antibody must simultaneously control the conformation of the individual reactants and their relation to each other. In the case of the disfavored process, binding energy must be used to reroute the reaction along a higher energy pathway. The rerouting of reaction pathways has become a major focus of antibody catalysis and other disfavored reactions can be expected to be catalyzed so long as the energy barrier is not extreme. The energy requirements needed for absolute control of all of the stereoisomers of many Diels-Alder reactions fall in the energy range (approximately 20 kilocalories per mole) deliverable by antibody binding. PMID- 8211140 TI - Molecular dynamics simulations of a lipid bilayer and of hexadecane: an investigation of membrane fluidity. AB - Molecular dynamics simulations of a fluid-phase dipalmitoyl phosphatidylcholine lipid bilayer in water and of neat hexadecane are reported and compared with nuclear magnetic resonance spin-lattice relaxation and quasi-elastic neutron scattering data. On the 100-picosecond time scale of the present simulations, there is effectively no difference in the reorientational dynamics of the carbons in the membrane interior and in pure hexadecane. Given that the calculated fast reorientational correlation times and the "microscopic" lateral diffusion of the lipids show excellent agreement with the experimental results, it is concluded that the apparently high viscosity of the membrane is more closely related to molecular interactions on the surface rather than in the interior. PMID- 8211139 TI - Detecting subtle sequence signals: a Gibbs sampling strategy for multiple alignment. AB - A wealth of protein and DNA sequence data is being generated by genome projects and other sequencing efforts. A crucial barrier to deciphering these sequences and understanding the relations among them is the difficulty of detecting subtle local residue patterns common to multiple sequences. Such patterns frequently reflect similar molecular structures and biological properties. A mathematical definition of this "local multiple alignment" problem suitable for full computer automation has been used to develop a new and sensitive algorithm, based on the statistical method of iterative sampling. This algorithm finds an optimized local alignment model for N sequences in N-linear time, requiring only seconds on current workstations, and allows the simultaneous detection and optimization of multiple patterns and pattern repeats. The method is illustrated as applied to helix-turn-helix proteins, lipocalins, and prenyltransferases. PMID- 8211141 TI - Mammalian locomotor-respiratory integration: implications for diaphragmatic and pulmonary design. AB - Diaphragmatic function and intrapulmonary respiratory flow in running mammals were found to differ substantially from the corresponding conditions known in resting mammals. In trotting dogs, orbital oscillations of the diaphragm were driven by inertial displacements of the viscera induced by locomotion. In turn, oscillations of the visceral mass drove pulmonary ventilation independent of diaphragmatic contractions, which primarily served to modulate visceral kinetics. Visceral displacements and loading of the anterior chest wall by the forelimbs are among the factors that contribute to an asynchronous ventilation of the lungs and interlobar gas recycling. Basic features of mammalian respiratory design, including the structure of the diaphragm and lobation of the lungs, appear to reflect the mechanical requirements of locomotor-respiratory integration. PMID- 8211142 TI - Resistance of mice deficient in IL-4 to retrovirus-induced immunodeficiency syndrome (MAIDS) AB - The murine acquired immunodeficiency syndrome (MAIDS) is induced by a defective murine leukemia virus and has many symptoms similar to those found in patients infected with the human immunodeficiency virus. The presence of both B cells and CD4+ T cells is critical for the development of the disease. Furthermore, a Th2 cytokine response dominates during the progression of the disease. When interleukin-4 (IL-4)-deficient mice that are defective in Th2 cytokine responses were infected, there was no lethality, and the development of the T cell abnormalities associated with MAIDS was delayed. These data suggest that IL-4 or a Th2 response is involved in the development of retrovirus-induced immunodeficiency in mice. PMID- 8211143 TI - Regional codon randomization: defining a TATA-binding protein surface required for RNA polymerase III transcription. AB - The TATA-binding protein (TBP) is required for transcription by all three nuclear RNA polymerases. TBP was subjected to regional codon randomization, a codon-based mutagenesis method that generates complex yet compact protein libraries. Analysis of 186 temperature-sensitive TBP mutants yielded 65 specifically defective in transcription by RNA polymerase III (Pol III). These mutants map to a limited TBP surface that may interact with Tds4, a component of the Pol III transcription factor TFIIIB. Strains that contain the Pol III-defective derivatives have increased amounts of messenger RNA, which suggests that competition among TBP interacting factors for limiting quantities of TBP determines the ratio of Pol II and Pol III transcription in vivo. PMID- 8211144 TI - Structure-based design of a cyclophilin-calcineurin bridging ligand. AB - The affinity of a flexible ligand that adopts a specific conformation when bound to its receptor should be increased with the appropriate use of conformational restraints. By determining the structure of protein-ligand complexes, such restraints can in principle be designed into the bound ligand in a rational way. A tricyclic variant (TCsA) of the immunosuppressant cyclosporin A (CsA), which inhibits the proliferation of T lymphocytes by forming a cyclophilin-CsA calcineurin complex, was designed with the known three-dimensional structure of a cyclophilin-CsA complex. The conformational restraints in TCsA appear to be responsible for its greater affinity for cyclophilin and calcineurin relative to CsA. PMID- 8211145 TI - An antiviral soluble form of the LDL receptor induced by interferon. AB - Interferons, which induce several intracellular antiviral proteins, also induce an extracellular soluble protein that inhibits vesicular stomatitis virus (VSV) infection. This 28-kilodalton soluble protein was purified to homogeneity and identified by protein sequencing as the ligand-binding domain of the human 160 kilodalton low density lipoprotein receptor (LDLR). The existence of an antiviral soluble LDLR was confirmed by immunoaffinity chromatography with monoclonal antibody to LDLR. This soluble receptor mediates most of the interferon-triggered antiviral activity against VSV, apparently by interfering with virus assembly or budding, and not by inhibiting virus attachment to cells. PMID- 8211146 TI - Long-term synaptic facilitation in the absence of short-term facilitation in Aplysia neurons. AB - Serotonin (5-HT) induces both short-term and long-term facilitation of the identified synaptic connections between sensory and motor neurons of Aplysia. Three independent experimental approaches showed that long-term facilitation can normally be expressed in the absence of short-term facilitation: (i) The 5-HT antagonist cyproheptadine blocked the induction of short-term but not long-term facilitation; (ii) concentrations of 5-HT below threshold for the induction of short-term facilitation nonetheless induced long-term facilitation; and (iii) localized application of 5-HT to the sensory neuron cell body and proximal synapses induced long-term facilitation in distal synapses that were not exposed to 5-HT and had not expressed short-term facilitation. These results suggest that short-term and long-term synaptic facilitation are induced in parallel in the sensory neurons and that the short-term process, because it is induced and expressed at the synapse, can occur locally, but the long-term process, because of its dependence on a nuclear signal, is expressed throughout the neuron. PMID- 8211147 TI - Mutation of glycine receptor subunit creates beta-alanine receptor responsive to GABA. AB - The amino acid at position 160 of the ligand-binding subunit, alpha 1, is an important determinant of agonist and antagonist binding to the glycine receptor. Exchange of the neighboring residues, phenylalanine at position 159 and tyrosine at position 161, increased the efficacy of amino acid agonists. Whereas wild-type alpha 1 channels expressed in Xenopus oocytes required 0.7 millimolar beta alanine for a half-maximal response, the doubly mutated (F159Y,Y161F) alpha 1 subunit had an affinity for beta-alanine (which was more potent than glycine) that was 110-fold that of the wild type. Also, gamma-aminobutyric acid and D serine, amino acids that do not activate wild-type alpha 1 receptors, efficiently gated the mutant channel. Thus, aromatic hydroxyl groups are crucial for ligand discrimination at inhibitory amino acid receptors. PMID- 8211148 TI - Whither directed mutation? PMID- 8211149 TI - Leading pork opponent hog-tied by cancer project. PMID- 8211150 TI - Copper clues clarify metabolic puzzle. PMID- 8211151 TI - Special issue: Science in Asia. PMID- 8211152 TI - The China-America connection. PMID- 8211153 TI - Singapore. Entering the scientific mainstream--selectively. PMID- 8211154 TI - China beckons to drug companies. PMID- 8211155 TI - From hepatitis to hepatoma: lessons from type B viral hepatitis. PMID- 8211156 TI - Proteases in Escherichia coli. PMID- 8211157 TI - Extending the Poisson approximation. PMID- 8211158 TI - Conformational flexibility of enzyme active sites. PMID- 8211159 TI - Human CksHs2 atomic structure: a role for its hexameric assembly in cell cycle control. AB - The cell cycle regulatory protein CksHs2 binds to the catalytic subunit of the cyclin-dependent kinases (Cdk's) and is essential for their biological function. The crystal structure of the protein was determined at 2.1 A resolution. The CksHs2 structure is an unexpected hexamer formed by the symmetric assembly of three interlocked dimers into an unusual 12-stranded beta barrel fold that may represent a prototype for this class of protein structures. Sequence-conserved regions form the unusual beta strand exchange between the subunits of the dimer, and the metal and anion binding sites associated with the hexamer assembly. The two other sequence-conserved regions line a 12 A diameter tunnel through the beta barrel and form the six exposed, charged helix pairs. Six kinase subunits can be modeled to bind the assembled hexamer without collision, and therefore this CksHs2 hexamer may participate in cell cycle control by acting as the hub for Cdk multimerization in vivo. PMID- 8211160 TI - HTLV-I Tax protein stimulation of DNA binding of bZIP proteins by enhancing dimerization. AB - The Tax protein of human T cell leukemia virus type-1 (HTLV-I) transcriptionally activates the HTLV-I promoter. This activation requires binding sites for activating transcription factor (ATF) proteins, a family of cellular proteins that contain basic region-leucine zipper (bZIP) DNA binding domains. Data are presented showing that Tax increases the in vitro DNA binding activity of multiple ATF proteins. Tax also stimulated DNA binding by other bZIP proteins, but did not affect DNA binding proteins that lack a bZIP domain. The increase in DNA binding occurred because Tax promotes dimerization of the bZIP domain in the absence of DNA, and the elevated concentration of the bZIP homodimer then facilitates the DNA binding reaction. These results help explain how Tax activates viral transcription and transforms cells. PMID- 8211161 TI - Structural features of polysaccharides that induce intra-abdominal abscesses. AB - The capsular polysaccharide complex from Bacteroides fragilis promotes the formation of intra-abdominal abscesses--a pathologic host response to infecting microorganisms. This complex consists of two distinct polysaccharides, each with repeating units that have positively charged amino groups and negatively charged carboxyl or phosphate groups. Analysis of these polysaccharides as well as other charged carbohydrates before and after chemical modification revealed that these oppositely charged groups are required for the induction of intra-abdominal abscesses in a rat model. PMID- 8211162 TI - Converting tissue plasminogen activator to a zymogen: a regulatory triad of Asp His-Ser. AB - Unlike most serine proteases of the chymotrypsin family, tissue-type plasminogen activator (tPA) is secreted from cells as an active, single-chain enzyme with a catalytic efficiency only slightly lower than that of the proteolytically cleaved form. A zymogenic mutant of tPA has been engineered that displays a reduction in catalytic efficiency by a factor of 141 in the single-chain form while retaining full activity in the cleaved form. The residues introduced in the mutant, serine 292 and histidine 305, are proposed to form a hydrogen-bonded network with aspartate 477, similar to the aspartate 194-histidine 40-serine 32 network found to stabilize the zymogen chymotrypsinogen. PMID- 8211163 TI - Expression of two T cell receptor alpha chains: dual receptor T cells. AB - Although many T cells carry two in-frame V alpha rearrangements, the products of both V alpha rearrangements have never been shown simultaneously on the surface of normal cells. With the use of monoclonal antibodies to V alpha 2, V alpha 12, and V alpha 24, up to one-third of mature T cells expressed two V alpha chains as part of two functional and independent T cell receptors (TCRs). Thus, the "one cell, one receptor" rule does not apply to a large subset of alpha beta T cells. Cells that belong to this dual TCR subset may be specific for a broader range of antigens than cells with a single receptor, which may be important for autoimmunity and alloreactivity. PMID- 8211164 TI - Altered fluid transport across airway epithelium in cystic fibrosis. AB - In cystic fibrosis (CF), absence or dysfunction of a phosphorylation-regulated chloride channel [CF transmembrane conductance regulator (CFTR)] leads to the loss or reduction of chloride secretion into the airways. Active sodium absorption is also increased in CF, and both of these ion transport changes could alter fluid transport across the airways. Under baseline conditions, cultured human airway epithelia from normal individuals absorbed fluid, and this absorption was increased in epithelia from patients with CF. In normal and CF epithelial cultures fluid absorption was inhibited by amiloride. Adenosine 3',5' monophosphate stimulated fluid secretion in normal epithelial cultures but not in cultures from individuals with CF. In contrast, fluid secretion induced by nucleotide triphosphates (uridine triphosphate or adenosine triphosphate) was unaltered in cultures of epithelia from patients with CF, suggesting an approach to the treatment of CF. PMID- 8211165 TI - Transcription-coupled DNA repair. PMID- 8211166 TI - The NIH Intramural Program. PMID- 8211167 TI - The NIH Intramural Program. PMID- 8211168 TI - Sex, violence, and sociobiology. PMID- 8211169 TI - Congress seeks files on gp160 vaccine. PMID- 8211170 TI - Rocky road for Federal Research Inc. PMID- 8211171 TI - Managing the genome data deluge. PMID- 8211172 TI - NIH, DOE battle for custody of DNA sequence data. PMID- 8211173 TI - Nobel Prizes. Medicine: discovery of genes in pieces wins for two biologists. PMID- 8211174 TI - Nobel Prizes. Chemistry: laurels for a late-night brainstorm. PMID- 8211175 TI - Nobel Prizes. Chemistry: changing the landscape of the possible. PMID- 8211176 TI - Medical centers of excellence and health reform. PMID- 8211177 TI - The political debate about health care: are we losing sight of quality? PMID- 8211178 TI - The future of DNA sequencing. PMID- 8211179 TI - The two-component pathway comes to eukaryotes. PMID- 8211180 TI - Germ-line gene modification and disease prevention: some medical and ethical perspectives. AB - There has been considerable debate about the ethics of human germ-line gene modification. As a result of recent advances in the micromanipulation of embryos and the laboratory development of transgenic mice, a lively discussion has begun concerning both the technical feasibility and the ethical acceptability of human germ-line modification for the prevention of serious disease. This article summarizes some of the recent research on germ-line gene modification in animal models. Certain monogenic deficiency diseases that ultimately might be candidates for correction by germ-line intervention are identified. Several of the most frequently considered ethical issues relative to human germ-line gene modification are considered in the context of professional ethics, parental responsibility, and public policy. Finally, it is suggested that there is merit in continuing the discussion about human germ-line intervention, so that this technique can be carefully compared with alternative strategies for preventing genetic disease. PMID- 8211181 TI - Arabidopsis ethylene-response gene ETR1: similarity of product to two-component regulators. AB - Ethylene behaves as a hormone in plants, regulating such aspects of growth and development as fruit ripening, flower senescence, and abscission. Ethylene insensitivity is conferred by dominant mutations in the ETR1 gene early in the ethylene signal transduction pathway of Arabidopsis thaliana. The ETR1 gene was cloned by the method of chromosome walking. Each of the four known etr1 mutant alleles contains a missense mutation near the amino terminus of the predicted protein. Although the sequence of the amino-terminal half of the deduced ETR1 protein appears to be novel, the carboxyl-terminal half is similar in sequence to both components of the prokaryotic family of signal transducers known as the two component systems. Thus, an early step in ethylene signal transduction in plants may involve transfer of phosphate as in prokaryotic two-component systems. The dominant etr1-1 mutant gene conferred ethylene insensitivity to wild-type Arabidopsis plants when introduced by transformation. PMID- 8211182 TI - Long-range attractive force between hydrophobic surfaces observed by atomic force microscopy. AB - There is evidence from atomic force microscopy for a long-range attractive force between hydrophobic surfaces that is virtually identical to that observed with the surface forces apparatus. This force is present in the nonaqueous solvent ethylene glycol. A possible molecular mechanism involves in-plane polarized domains of solid-like monolayers adsorbed on mica, and a theoretical model has been developed that accounts for many of the observations. PMID- 8211183 TI - A yeast protein similar to bacterial two-component regulators. AB - Many bacterial signaling pathways involve a two-component design. In these pathways, a sensor kinase, when activated by a signal, phosphorylates its own histidine, which then serves as a phosphoryl donor to an aspartate in a response regulator protein. The Sln1 protein of the yeast Saccharomyces cerevisiae has sequence similarities to both the histidine kinase and the response regulator proteins of bacteria. A missense mutation in SLN1 is lethal in the absence but not in the presence of the N-end rule pathway, a ubiquitin-dependent proteolytic system. The finding of SLN1 demonstrates that a mode of signal transduction similar to the bacterial two-component design operates in eukaryotes as well. PMID- 8211184 TI - U2AF homolog required for splicing in vivo. AB - Several fission yeast temperature-sensitive mutants defective in pre-mRNA processing (prp- mutants) at the nonpermissive temperature have been identified. Here, the prp2+ gene has been cloned by its ability to complement the temperature sensitive growth defect of a prp2- mutant. The gene also corrects the pre-mRNA splicing defect of prp2- mutants and encodes a 59-kilodalton polypeptide (PRP2). A molecular characterization indicates that PRP2 is a previously uncharacterized yeast splicing factor with extensive similarity to the mammalian splicing factor U2AF65. Thus, this study provides evidence that a U2AF homolog participates in RNA processing in vivo. PMID- 8211185 TI - Potentiation by the beta subunit of the ratio of the ionic current to the charge movement in the cardiac calcium channel. AB - The voltage-activated rabbit cardiac calcium channel alpha 1 subunit was expressed in Xenopus oocytes. The charge movement of its voltage sensor was measured and related to the opening of the ion-conducting pore. The half activation potential for charge movement was 35 millivolts more negative than that for pore opening. Coexpression of the cardiac calcium channel beta subunit reduced this difference without affecting charge movement. Thus, intramolecular coupling between the voltage sensor and the channel pore opening can be facilitated by a regulatory subunit. PMID- 8211186 TI - Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. AB - Genetic and metabolic studies have been done on a large kindred in which several males are affected by a syndrome of borderline mental retardation and abnormal behavior. The types of behavior that occurred include impulsive aggression, arson, attempted rape, and exhibitionism. Analysis of 24-hour urine samples indicated markedly disturbed monoamine metabolism. This syndrome was associated with a complete and selective deficiency of enzymatic activity of monoamine oxidase A (MAOA). In each of five affected males, a point mutation was identified in the eighth exon of the MAOA structural gene, which changes a glutamine to a termination codon. Thus, isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression. PMID- 8211187 TI - Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type 1a. AB - Glycogen storage disease (GSD) type 1a is caused by the deficiency of D-glucose-6 phosphatase (G6Pase), the key enzyme in glucose homeostasis. Despite both a high incidence and morbidity, the molecular mechanisms underlying this deficiency have eluded characterization. In the present study, the molecular and biochemical characterization of the human G6Pase complementary DNA, its gene, and the expressed protein, which is indistinguishable from human microsomal G6Pase, are reported. Several mutations in the G6Pase gene of affected individuals that completely inactivate the enzyme have been identified. These results establish the molecular basis of this disease and open the way for future gene therapy. PMID- 8211188 TI - Cyclic ADP-ribose in beta cells. PMID- 8211189 TI - Empathy: the guiding value for health care reform. PMID- 8211190 TI - A profile of SD nurses with advanced education: survey results. PMID- 8211191 TI - Recurrent cutaneous melanoma: a surgical perspective. PMID- 8211192 TI - Considerations for reconstruction after surgery for recurrent cancer. AB - Refinements in our knowledge of the anatomy and physiology of myocutaneous and fasciocutaneous flaps has served as the impetus to apply these modalities to achieve healed, stable wounds in areas undergoing wide exenterative resection for recurrent rectal carcinoma. The adverse effects on tissue from adjuvant or therapeutic radiation therapy is greatly ameliorated by these healthy nonirradiated tissues, which serve as a conduit for oxygen as well as humeral and cellular factors to enhance the immune response as well as to aid wound healing. Moreover, refinements in surgical technique have allowed the reconstructive surgeon to Radical ablative surgery is possible because of the advances over the past half century in our understanding of cancer, surgical principles, anesthesia, preoperative preparation, and postoperative support. It can be argued that radical ablation without reconstruction promises increased quantity of life, which is only half of the equation. Only quality of existence can make even a few more months of life truly meaningful for a patient. This is the real contribution of reconstruction. It is with the expectation that form and function can be restored toward the premorbid state that the surgical oncologist can confidently recommend radical salvage procedures that provide both quantity and quality of life. PMID- 8211193 TI - Treatment of intrathoracic recurrent non-small-cell lung cancer. PMID- 8211195 TI - Diagnosis and management of distant recurrence in soft-tissue sarcomas. AB - Understanding of the patterns of, and treatments for, metastatic disease from soft-tissue sarcoma is of vital importance in caring for these patients. Metastasis can occur independently of adequate local control. When metastasis occurs, it usually causes no symptoms. Thus, all patients with malignant soft tissue sarcomas must be followed with a careful surveillance regimen. When metastasis is discovered, the overriding goals of surgical treatment must be total resection of all tumor with the minimal loss of functional lung tissue. Multiple subsequent resections may be needed for recurrent metastasis but the goals remain the same. Postoperative chemotherapy may be of benefit in eradicating residual micrometastases. With ongoing research and the advent of more effective and better-tolerated adjuvant therapies, we should continue to make progress obtaining better cure rates and longer duration of survival for these patients. PMID- 8211194 TI - Diagnosis and surgical management of locally recurrent soft-tissue sarcomas of the extremity. AB - The patient who presents with evidence of a recurrent soft-tissue sarcoma of the extremity should have a complete history and physical examination. A diagnostic biopsy, either fine-needle or open biopsy, should be performed to confirm recurrence. Liver-function tests, complete blood cell count, electrolytes, and chest X-ray should be performed. If preliminary evaluation confirms local recurrence and is negative for regional or distant disease, a CT scan of the chest to better exclude metastases, as well as a CT or MRI of the local recurrence, should be performed. If neurovascular structures appear at risk on noninvasive scanning, an arteriogram is performed to exclude major vascular involvement. In selected circumstances, arterial and/or venous reconstruction may be indicated to allow complete gross removal of tumor. Complete removal of tumor should be combined with radiotherapy for all sarcomas with close margins and for any high-grade lesion regardless of margin status. Brachytherapy can often be used even when the patient has had prior teletherapy to the site. Complete tumor removal combined with adjuvant radiotherapy is the best way to prevent subsequent local recurrence and provide long-term survival. PMID- 8211196 TI - Surgical management of recurrent genitourinary malignancies. PMID- 8211197 TI - Surgical management of recurrent liver tumors. AB - Hepatic resection remains the only potentially curative treatment modality for patients with primary and secondary malignant hepatic tumors. Unfortunately, most patients undergoing resection will develop recurrent disease. Aggressive local treatment of recurrent disease should be considered for patients with recurrence limited to the liver after an initial "curative" hepatic resection. In these patients, repeat hepatic resection can be performed safely and may result in long term DFS. The decision to perform a repeat hepatic resection must currently be based on the same guidelines as used in selecting a patient for an initial hepatic resection: a limited number of metastases, the technical ability to resect all gross disease, satisfactory general medical condition of the patient, and adequate functional hepatic reserve. Cryotherapy is presently the only alternative to resection that may offer patients with intrahepatic recurrence a chance for long-term disease control. Although many questions remain regarding the ultimate role of cryotherapy and because current technology limits the size of lesions that can be successfully treated, experience to date indicates that it may be comparable to resection for some patients. Combinations of resection, cryotherapy, and regional chemotherapy may expand the population of patients with recurrent hepatic disease that may be managed surgically. Further evaluation of these treatment modalities in clinical trials will establish their ultimate role in the management of recurrent primary and secondary hepatic malignancies. PMID- 8211198 TI - Isolated locally recurrent rectal cancer: a review of incidence, presentation, and management. AB - Locoregional recurrence after treatment for rectal cancer may be largely prevented by wide pelvic surgical margins, adjuvant radiotherapy, and chemotherapy. Approximately half of these recurrences will present with recurrence only at the surgical site; one third to one half will be resectable with conventional surgical procedures, but the rest will require extended resections, including sacrum and hypogastric vessels, to achieve clean margins. Only a small fraction of those treated will be cured. There is no proof that radiotherapy or chemotherapy added to surgical excision afford better results, since no trials have been or are likely to occur, given the rarity of the situation. However, best results seem to follow multimodality therapy using complete surgical resection and radiotherapy (IORT or brachytherapy with or without teletherapy) with chemopotentiation. Yet, there is no multimodality series with a sufficient number of patients and follow-up period to be able to distinguish the actual value of the treatment and which patients are most likely to benefit. It is important to note that there will be some patients with second LRR who can be further aided by aggressive locoregional therapy. PMID- 8211199 TI - Surgical considerations in nonhepatic intra-abdominal recurrence of carcinoma of the colon. PMID- 8211200 TI - Nutritional consequences of reoperative surgery in recurrent malignancy. PMID- 8211201 TI - Biologic therapies for low-grade lymphomas. PMID- 8211202 TI - Monoclonal antibody therapy for indolent lymphomas. PMID- 8211203 TI - Bone marrow transplantation for indolent lymphomas. PMID- 8211205 TI - Histopathologic subtypes of indolent lymphomas: caricatures of the mature B-cell system. PMID- 8211204 TI - Monitoring minimal residual disease. PMID- 8211206 TI - Molecular biology of lymphomas. PMID- 8211207 TI - Cytogenetics of indolent lymphomas. PMID- 8211208 TI - Immunobiologic correlates of prognosis in lymphoma. PMID- 8211209 TI - Natural history of and therapy for the indolent non-Hodgkin's lymphomas. PMID- 8211210 TI - Prognostic factors in follicular lymphomas. PMID- 8211211 TI - The platelet-refractory bone marrow transplant patient: prophylaxis and treatment of bleeding. AB - Refractoriness to platelet transfusions remains a significant problem for oncology patients, occurring in 30% to 70% of multiply transfused recipients with bone marrow failure. Nonimmune causes are often present and include disseminated intravascular coagulation, concurrent use of amphotericin B, infection, presence of palpable spleen, use of antibacterial antibiotics, bleeding, veno-occlusive disease, and fever. Immune causes are also commonly responsible for refractoriness, with HLA alloimmunization dominating the list of immune factors. HLA antibodies can be identified in 25% to 30% of transfused leukemia patients and can be present in as many as 80% of aplastic anemia patients. Developing a consistent approach to managing these refractory patients is essential to preventing and treating bleeding manifestations. An HLA type should be obtained for all patients anticipated to have chronic transfusion requirements. Screening for lymphocytotoxic antibodies can confirm suspected HLA alloimmunization. Histocompatible platelets (cross-match compatible and HLA matched) should be provided for all patients with HLA antibodies. A number of other therapeutic modalities have been used in an effort to manage the alloimmunized patient; most of these methods have had little or no proven benefit. When bleeding develops in the alloimmunized patient, there are few therapeutic choices. If histocompatible platelets are unavailable or unsuccessful, massive platelet transfusions of pooled platelet concentrates are commonly used, although this practice is of no proven benefit. While antifibrinolytic agents have been available for over 30 years, they are only recently being applied to control bleeding in chronic thrombocytopenia. We have successfully managed bleeding episodes in thrombocytopenic bone marrow transplant recipients with the use of epsilon aminocaproic acid. A number of these patients were platelet refractory with demonstrable platelet antibodies. Platelet refractoriness continues to plague multiply transfused oncology patients. While preventative measures may ultimately benefit some patients, this problem will continue to manifest itself. A consistent approach to transfusion support needs to be implemented to best manage this challenging patient population. PMID- 8211212 TI - Peripheral blood and bone marrow hematopoietic stem cells: are they the same? AB - Hematopoietic stem cells collected from the peripheral blood (PBSCs) have been successfully used for transplantation. Originally, these cells, collected from patients with chronic myelogenous leukemia, were used to restore chronic phase of the disease. More recently, PBSCs have been used principally for autologous transplantation for nonhematologic malignancies, although there are a few recorded cases of allogeneic transplantation with PBSCs. The process of obtaining peripheral blood stem cells is tedious in comparison to the process of harvesting bone marrow for transplantation, requiring multiple lengthy apheresis procedures to collect sufficient cells for transplant. Moreover, the risks associated with PBSC collection (anesthesia risk for catheter placement, risk of introducing infection during collection) are just as great as those associated with marrow harvesting. However, for the patient whose bone marrow is unharvestable due to hypocellularity or fibrosis, PBSC transplantation may reopen the option of treatment by high-dose cytotoxic therapy and autologous hematopoietic stem cell rescue. Peripheral blood stem cell transplantation may also afford the transplant option to the patient whose marrow has been infiltrated with disease. While it has not been demonstrated, it is hypothetically likely that the probability of tumor cell contamination of circulating blood is quite low, due to the lack of adherence necessary for colonization. Recent reports have indicated that autologous transplantation with PBSCs may result in more rapid engraftment relative to autologous transplantation with bone marrow. This has only been reported in programs wherein PBSCs are collected under mobilizing conditions. If it is the case that PBSCs produce more rapid engraftment, however, then the additional effort and cost associated with PBSC collection might be outweighed by the reduced morbidity, mortality, and cost associated with early return of granulocytes in the transplant patient. The biology of the early engraftment phenomenon should be studied, as it is possible that it is related to the mobilizing conditions under which the cells are collected and not due to an intrinsic quality of PBSCs. PMID- 8211213 TI - Optimizing high-dose therapy using pharmacokinetic principles. AB - The oncologic literature of the past decade contains numerous articles supporting the concept of "dose intensity." The hypothesis that greater intensity of effective drug therapy can result in higher cure rates is supported by the results obtained in bone marrow transplantation for leukemia, lymphoma, and, possibly, breast carcinoma. Stem cell infusion overcomes the first level of the dose-limiting toxicities, ie, bone marrow suppression. This predictable toxicity develops in all patients. Second organ toxicities, such as renal, hepatic, or cardiopulmonary toxicity, occur in a less predictable manner. This variation in individual patient tolerance may be related to wide variations in drug concentration between patients while receiving the same dose. This interpatient variability has been well described for many oncologic agents, but is not unique to oncologic therapy. Important but incompletely defined relationships of importance to high-dose therapy include (1) the relationship of drug dose to concentration within patient groups and for the individual patient and (2) the relationship of drug concentration, or other related parameter such as area under the concentration versus time curve, to toxicity and outcome. Assuming such relationships can be defined, the value of using improved methods to select drug doses for an individual patient to achieve therapeutic goals needs to be explored. The purpose is to optimize therapy. In the bone marrow transplantation setting, the ideal is to provide the greatest drug exposure without undo risk of life-threatening second organ toxicity. To solve these problems, we need models that predict and allow us to control therapy in a much more precise manner than is currently possible. This review examines the concept of dose intensity, defines this concept in terms of plasma drug concentrations, and reviews methods that can aid the control of therapy in the individual patient. The potential importance of this methodology to the individual patient is discussed. PMID- 8211214 TI - Lymphocyte depletion in bone marrow transplantation: will modulation of graft versus-host disease prove to be superior to prevention? AB - Despite its detrimental effects, graft-versus-host disease (GVHD) has antileukemic properties as evidenced by a lower relapse rate in patients who develop GVHD following allogenic bone marrow transplantation. Meaningful long term survival may be achieved if this latter property can be retained at the same time that the deleterious immune sequelae of acute and chronic GVHD are diminished. This is the focus of several recent graft engineering protocols. Various bone marrow components (lymphocytes, hematopoietic stem cells, and committed progenitor cells) can now be isolated and then used to reformulate the marrow graft. Combined with host immunosuppression or cytokine augmentation, it now may be possible to modulate GVHD such that its beneficial properties are enhanced without incurring its life-threatening side effects. PMID- 8211215 TI - Autologous bone marrow transplantation for leukemia. AB - Autologous bone marrow transplantation for leukemia was developed to extend the apparent curative potential of myeloablative therapy with allogeneic bone marrow transplantation to leukemia patients without histocompatible marrow donors. The conceptual problem with this approach is obvious: if the need for the transplant is based on overt or occult contamination of the marrow by leukemia, the use of autologous marrow seems destined to failure because of reinfusion of leukemia cells along with the harvested marrow. For this reason, ex vivo antileukemic treatment ("purging") of remission marrow was developed to justify autologous transplants for leukemia. Clinical trials involving thousands of patients worldwide have demonstrated curative potential of autologous bone marrow transplants, using purged or untreated remission marrow, for selected patients with acute myelogenous leukemia and acute lymphocytic leukemia. Purging appears to contribute to increased leukemia-free survival, at least in a subset of patients who are at very high risk of relapse, but this has not been tested in a prospective randomized trial and remains controversial. In acute myelogenous leukemia, in which the greatest experience exists, procedure-related mortality is much less for autologous than for allogeneic transplants; however, since leukemia relapse is much more frequent for autologous than for allogeneic transplants, the long-term disease-free survival is similar. In general, autologous transplants are preferred for older individuals and those without matched related donors, whereas allogeneic transplants are preferred for younger patients with matched related donors. Leukemia relapse has greatly limited the success of autologous transplants for acute lymphocytic leukemia. Autologous transplants for the chronic leukemias are in a much earlier stage of investigation. Autologous transplantation for leukemia is a fertile area for research. Important topics include conditioning regimens with improved antileukemic efficacy, the value of purging and the best method(s) for leukemia stem cell purging or normal stem cell selection, the possibility of inducing an autologous graft versus leukemia reaction, the use of immunomodulatory cytokines for postgrafting immune system manipulation, and the use of hematopoietic growth factors for ex vivo stem cell expansion and postgrafting support of marrow recovery. PMID- 8211216 TI - Autologous bone marrow transplantation in the treatment of breast cancer: clinical and technologic strategies. AB - Autologous bone marrow transplantation has permitted the clinical investigation of dose-intense chemotherapy for solid tumors as well as hematologic malignancies. The most widely studied solid tumor is breast cancer, the most common malignant disease cause of death in women under the age of 55 years in the United States. Promising results in terms of disease-free, chemotherapy-free survival have been achieved for patients with low-dose chemotherapy-sensitive metastatic disease. Issues such as the selection of drugs to be used in combination chemotherapy for both the induction phase and the high-dose therapy phase, the timing of high-dose therapy, the role of peripheral stem cells, and marrow purging remain under intensive investigation. The rational extension of this strategy into the adjuvant and neoadjuvant settings is also under study. PMID- 8211217 TI - Two novel high-dose treatment regimens for metastatic breast cancer--ifosfamide, carboplatin, plus etoposide and mitoxantrone plus thiotepa: outcomes and toxicities. AB - This report describes the results of two phase I/II dose escalation trials for the treatment of metastatic breast cancer. Successive groups of patients with metastatic breast cancer responsive to induction therapy following standard doses of chemotherapy were treated with escalating doses of ifosfamide (6,000 to 24,000 mg/m2), carboplatin (1,200 to 2,100 mg/m2), and etoposide (1,800 to 3,000 mg/m2) followed by autologous stem cell rescue. The maximum tolerated doses of these drugs were defined as ifosfamide 20,100 mg/m2, carboplatin 1,800 mg/m2, and etoposide 3,000 mg/m2. Major nonhematologic toxicity consisted of mucositis and enteritis, and the dose-limiting toxicities were central nervous system toxicity and acute renal failure. The overall treatment-related mortality rate was 4%. The event-free survival rate at 500 days for these patients was 31%. Patients with metastatic breast cancer refractory to all standard dose therapy were treated with escalating doses of mitoxantrone (45 to 105 mg/m2) and thiotepa (900 to 1,350 mg/m2) followed by autologous stem cell rescue. The maximum tolerated doses of these drugs were defined as mitoxantrone 90 mg/m2 and thiotepa 1,200 mg/m2 with mucositis and enteritis as the major nonhematologic toxicities and delayed myelosuppression as the dose-limiting toxicity. Twelve percent of the patients remain event free at 500 days and the treatment-related mortality rate for this group of heavily pretreated patients was 17%. These data suggest that patients with metastatic breast cancer may benefit from high-dose therapy and that treatment-related toxicity is tolerable. PMID- 8211218 TI - Allogeneic bone marrow transplantation for multiple myeloma. AB - Allogeneic bone marrow transplantation remains the only therapeutic approach with documented curative potential for patients with multiple myeloma. A survey of recently published trials reveals a 40% long-term survival rate with no evidence of residual disease in a majority of patients. While morbidity and mortality from myelosuppression and graft-versus-host disease are relatively high, allogeneic bone marrow transplantation should be considered early in the course of treatment for patients with high-risk myeloma. PMID- 8211219 TI - Autologous bone marrow transplantation for the treatment of lung cancer. AB - Non-small cell lung cancer is extremely difficult to treat in all stages, and small cell lung cancer patients are cured rarely despite initial responsiveness to conventional chemoradiation therapy, even when diagnosed in limited stage. Intensive cytotoxic therapy has been explored in both small cell and non-small cell lung cancer patients, since a number of agents showed an increased response when given in high dose followed by autologous bone marrow reinfusion. The antitumor responses of single-agent high-dose trials were short-lived, but set the stage for combination chemotherapy trials given in earlier disease stages, ie, as consolidation or intensification therapy in lung cancer. In 11 published trials, 204 small cell lung cancer patients have undergone autologous bone marrow transplants. Although the transplant-related mortality rate in these studies was 7%, the long-term disease-free survival rate was 14% in a heterogeneous group of patients receiving a variety of regimens. The data gleaned from these studies suggested that a subpopulation of lung cancer patients may benefit from the use of this approach if it were to be administered at a time when the tumor burden was low. Because of the great cost of this procedure, however, third-party payers seldom provide financial coverage for these procedures. Hence, while great strides have been made in the therapy of other solid tumors, such as breast, testicular, and ovarian cancers, the role of autologous stem cell transplantation in small cell and non-small cell lung cancer remains yet to be defined. PMID- 8211220 TI - Infections in allogeneic bone marrow transplant recipients. AB - Remarkable strides have been made in the management of infectious complications after bone marrow transplantation. Improved understanding of patterns of infection, the introduction of new antimicrobials, the advent of cytokines to enhance immune recovery, the development of better strategies to control graft versus-host disease, and the availability of more accurate and rapid diagnostic assays have all contributed to reducing the morbidity and mortality from infection after allogeneic marrow transplantation. PMID- 8211221 TI - Growth factors in allogeneic transplantation. AB - Several variables contribute to the successful outcome of allogeneic bone marrow transplantation. During the first 4 weeks after reinfusion of allogeneic marrow, morbidity and mortality rates related to pancytopenia are high. After this time the development of graft-versus-host disease and/or recurrence of malignancy may further increase morbidity and limit survival. Hematopoietic growth factors such as recombinant human granulocyte-macrophage and recombinant human granulocyte colony-stimulating factors reduce morbidity of patients receiving high-intensity chemotherapy regimens by stimulating earlier neutrophil recovery. Studies in allogeneic bone marrow transplantation patients who receive recombinant human granulocyte-macrophage, recombinant human granulocyte, and recombinant human macrophage colony-stimulating factors suggest that these factors are well tolerated. The severity of graft-versus-host disease is not adversely affected, morbidity is less, and survival may be improved in certain patient populations. Results of phase I and II trials with hematopoietic growth factors in patients undergoing allogeneic bone marrow transplantation will be reviewed. PMID- 8211222 TI - Red blood cell deformability, membrane material properties and shape: regulation by transmembrane, skeletal and cytosolic proteins and lipids. AB - An unusual combination of membrane properties allows the RBC to undergo extensive deformation without cell fragmentation, enabling it to effectively perform its function of oxygen delivery during its long life span in circulation. These material properties are the consequence of slow evolution-driven "engineering" which evolved a composite structure in which a plasma membrane envelope composed of amphiphilic surfactant molecules is anchored to a network of skeletal proteins through tethering sites (transmembrane proteins) in the bilayer. Explosive growth in our understanding of the primary structure of the various RBC membrane proteins, definition of specific mutations in various RBC phenotypes, and detailed biophysical characterization of membrane properties of normal and mutant RBCs has enabled development of models of the molecular and structural basis for RBC properties. In this review, we have attempted to synthesize all of this currently available information and define the contributions of various membrane components to different RBC properties. PMID- 8211223 TI - Rh blood group antigens: protein and gene structure. PMID- 8211224 TI - The Kell blood group system and the McLeod phenotype. PMID- 8211225 TI - The glycolipid anchor of membrane surface proteins. PMID- 8211226 TI - The red blood cell and malaria parasite invasion. PMID- 8211227 TI - Case of the season. Invasive lobular carcinoma. PMID- 8211228 TI - Breast cancer: incidence, risks, and primary and adjuvant therapy. PMID- 8211229 TI - Mammographic screening: an historical perspective. PMID- 8211230 TI - Mammographic feature analysis. PMID- 8211231 TI - Nonmammographic imaging of the breast: current issues and future prospects. PMID- 8211232 TI - Preoperative localization of breast lesions: tailored techniques and potential pitfalls. AB - Preoperative needle localization procedures can be performed using a variety of devices and tailored approaches. Success in these endeavors can be optimized through communication and coordination among the radiologist, surgeon, and pathologist. Meticulous attention to performance and radiological-pathological correlation are required to ensure the best possible results. PMID- 8211233 TI - The roles of needle biopsy and periodic follow-up in the evaluation and diagnosis of breast lesions. PMID- 8211234 TI - Pathology of the breast. PMID- 8211236 TI - Conservative surgery and radiation for early-stage breast cancer. AB - In selected patients with early-stage breast cancer, conservative surgery and radiation represent an alternative equal to mastectomy in terms of local recurrence, distant metastasis, survival, and long-term complications. Patients with early-stage breast cancer who are candidates for conservative surgery and radiation include those whose primary tumor is less than 4 to 5 cm in size without evidence of gross multicentricity or diffuse microcalcifications. Patients with an extensive intraductal component may be appropriate candidates provided that margins of resection are negative. Young age is not a contraindication to the conservative treatment. A preexisting history of collagen vascular disease or prior mantle irradiation for Hodgkin's or non-Hodgkin's lymphoma represents a contraindication to conservative surgery and radiation because of the potential for severe complications. An additional contraindication is the pregnant woman in whom delivery cannot be accomplished before the initiation of radiation. Mammography is essential in the pretreatment evaluation and posttreatment follow-up of the conservatively treated patient. The goal of the pretreatment mammogram is to assess the extent of disease in the ipsilateral breast as well as to evaluate the contralateral breast. In patients who present with microcalcifications, a postbiopsy mammogram before radiation is essential to document complete removal of all malignant-appearing microcalcifications. Mammography is an essential part of the follow-up program in order to detect a recurrence in the treated breast as well as a cancer in the contralateral breast cancer. The optimal interval for follow-up mammography has not been determined, although programs employing mammography on a yearly basis after treatment have been associated with the detection of early recurrences and excellent survival after salvage mastectomy for these recurrences. PMID- 8211235 TI - Carcinoma of the breast. PMID- 8211237 TI - [Nurses and the representations of nursing. Some ideas and facts]. PMID- 8211239 TI - [Drug liberalization: yes or no]. PMID- 8211238 TI - [Liberty and clearheadedness--the drug problem]. PMID- 8211240 TI - [The use of touch in the interaction between nurse and the elderly patient in an institution]. PMID- 8211241 TI - [Rapid neurological assessment]. PMID- 8211243 TI - [Home care in Denmark]. PMID- 8211242 TI - [Arterial hypertension in the elderly]. PMID- 8211244 TI - [The personal and interpersonal dimension of the educational relationship]. PMID- 8211246 TI - [When should a cataract be operated on?]. PMID- 8211245 TI - [The recuperation of the elderly after a coronary artery bypass]. PMID- 8211247 TI - [Death in the hospital]. PMID- 8211248 TI - Prostate cancer screening: getting your patients to follow-up. AB - Nurses have the clinical knowledge and organizational ability to carry out a quality prostate cancer screening program. In addition, nurses possess the communication and patient education skills necessary for effective follow-up. With the dramatic increase in prostate screening programs, nurses are likely to be among the leaders in this effort. Motivating patients to follow up when they have an abnormal DRE or serum PSA can increase the early detection of prostate cancer and potentially cure the disease. After all, this is the primary purpose of the screening. PMID- 8211249 TI - Nursing management for patients using external vacuum devices: a unique opportunity. PMID- 8211250 TI - Liquidate a myth: reducing liquid intake is not advisable for elderly with urine control problems. PMID- 8211251 TI - Fundamental urodynamics. Part 1. Normal bladder function and patient assessment. PMID- 8211252 TI - Spina bifida. Part 2. Family issues and psychosexual concerns. AB - This brief overview of family issues and psychosexual concerns should provide the reader with the stimulus to explore the many issues surrounding the birth of a child with spina bifida. Only two issues were presented in the care and management of children with spina bifida. There are many others, such as the financial burden imposed by multiple health care visits, that have an impact on the total treatment of the individual with spina bifida. Because of advances in the medical and surgical management of individuals with spina bifida, the life expectancy of individuals with spina bifida is expanded; as more individuals reach adulthood and beyond, other issues will emerge. It is the responsibility of the health care professional to devise methods to assist individuals with spina bifida to maximize their abilities and live a productive life. PMID- 8211253 TI - A prostate cancer support group: does it work? PMID- 8211254 TI - The six-bottle voiding routine. PMID- 8211256 TI - Women and tropical diseases. PMID- 8211255 TI - Women and tropical diseases. Introduction. PMID- 8211257 TI - Leprosy in women: characteristics and repercussions. AB - "Health is often measured in terms of low mortality; nevertheless, merely being alive is not a measure of the quality of life" H. Mendez Castellanos. Physiological, socioeconomic and cultural factors play important roles in the response of women to Mycobacterium leprae and in the impact of leprosy on their lives. They appear to develop stronger immunological responses to M. leprae than men, as suggested by lower incidence and less severe clinical forms of disease in most areas of the world, as well as stronger reactions of cell-mediated immunity after prophylactic vaccination. Genetic factors and physiological status including pregnancy, intercurrent infection and malnutrition might be among the factors which modulate this response. Women in leprosy-endemic areas of the world, with few exceptions, suffer from marked economic and social dependency and inferiority which can only be heightened by the social stigma associated with leprosy. Nevertheless, they bear an enormous responsibility for the health of their families, often as head of the household, and they often possess a unique capacity to influence community opinion. With the introduction of multidrug therapy, leprosy control throughout the world is no longer an unrealistic goal. Active vaccination may constitute the other factor necessary for eventual eradication of the disease. The incorporation of women at all levels into active roles in health care programs may constitute one of the decisive factors in the success or failure of leprosy control. PMID- 8211258 TI - An historical and clinical review of the interaction of leprosy and pregnancy: a cycle to be broken. AB - Since earliest history the person with leprosy has been shut out from society. Laws have prohibited marriage and allowed divorce of those with leprosy. Segregation of the sufferer from the rest of society has been followed by separation of the sexes, and of leprous parents from their children. With the advent of antileprotic drugs, first dapsone then multidrug therapy (MDT), infection can be treated, individuals made non-infectious, and the pool of infection in the community reduced. The clinical signs of leprosy are due not to the degree of infection but to the immunological status of the host. Hormonal changes at puberty and in pregnancy can cause variation of the host's immune status. Pregnancy in women with leprosy is a hazardous undertaking. First appearance of leprosy, reactivation of the disease and relapse in 'cured' patients is likely to occur particularly in the third trimester of pregnancy. Leprosy reactions caused by variation in cell mediated and humoral immunity are triggered off by pregnancy: type 1 reaction (reversal reaction, RR) occurs post partum, while type 2 reaction (erythema nodosum leprosum, ENL) peaks in late pregnancy. Both types of reaction continue long into lactation. Neuritis with loss of both sensory and motor function is associated with relapse and reaction. Relapse, reaction and nerve damage, especially 'silent neuritis', with subsequent deformity and disability, occur not only in women on apparently effective treatment but also in those who have received MDT and have been released from treatment (RFT). To prevent disability, research is urgently needed into the mechanisms of early and late reaction and neuritis. Pregnancy is not only a trigger factor for reaction but an ideal in vivo model for research. Up to 20% of children born to mothers with leprosy may develop leprosy by puberty. While early leprosy in young children is self-healing, when marriage and childbearing take place at an early age the daughters of mothers with leprosy are likely to run the risk of experiencing the adverse effects of pregnancy on leprosy. Increased awareness and health education, as well as long term surveillance of 'cured' leprosy patients, are essential to break a potentially vicious cycle of leprosy and pregnancy. Women with cured leprosy could play an important role in screening for and detection of both early leprosy in children and late, post-MDT RFT, nerve damage in their mothers. PMID- 8211260 TI - Bilharzia and the boys: questioning common assumptions. AB - There is insufficient and inadequate information to gauge the impact of schistosomal infection on the health of women. Biomedical research has equated women's health with the study of reproductive performance and reproductive organs and this narrow focus has left a number of important questions unanswered. Attempts to explore the economic and social aspects of schistosomal infection have been minimal and most research has focused on men rather than women. It has two characteristics: first, economists have relied on single performance indicators which are rooted in the cultural traditions of the research workers rather than the participants. Second, questionnaires have been used to elicit perceptions of health and illness; and local, culturally-specific information has not even been used to formulate the questions. Future research assessing the social and economic aspects of infection among women would be enhanced by undertaking inter-disciplinary research, with an ethnographic component; and blending qualitative with quantitative methods. Research assessing the impact of schistosomal infection on daily activities has been undertaken in Omdurman aj Jadida, Sudan. Biomedical and continuous observational data were blended with ethnographic information and the analyses of these data suggest that Schistosoma mansoni exerts a differential impact on female activity patterns. That is, infection by S. mansoni significantly impaired female activities in the agricultural sphere whereas infection by S. mansoni did not have any significant impact on female activities in the domestic sphere. Variations in the nature and extent of work undertaken by these two groups of women as well as differential exposure to solar radiation probably accounts for these recorded differences. The limited and tentative nature of biomedical, economic, sociological and anthropological information assessing the impact of schistosomal infection on the health of women adds to the current controversies about whether schistosomiasis should continue to be given priority as a public health problem. Further research is essential to clarify this important issue. PMID- 8211259 TI - Women and malaria--special risks and appropriate control strategy. AB - This paper reviews the factors which make non-immune pregnant women particularly vulnerable to falciparum malaria and examines the problems of adequately protecting them in relation to current control strategies. Women are most at risk in areas of high and continuous transmission, particularly during their first pregnancy, and also under conditions of unstable malaria which do not permit immunity to develop. Chemoprophylaxis is recommended for pregnant women in holoendemic and hyperendemic areas in Africa and Papua New Guinea. Chloroquine is safe, but drug resistance problems are beginning to limit its utility. Distribution is a formidable problem in rural areas with a poorly developed health care infrastructure, and research studies reveal widespread ignorance and lack of motivation. In countries in which primary health care systems are fairly well developed, and where malaria transmission is relatively less intense, the emphasis is on early diagnosis and treatment of cases. The assumption is made that women and men have equal access to medical facilities. The preponderance of reported cases among adolescent and adult males in some areas has been attributed solely to the well-known greater occupational risks in some traditionally male activities. Two recent studies, however, suggest that underprivileged women, weighed down by domestic chores, do not readily attend clinics at some distance from home, and therefore are liable to be missed in passive surveillance. It is essential that services within the village should be strengthened, but there are problems in implementation. Lacunae in existing knowledge are discussed. PMID- 8211261 TI - Adam's rib awry? Women and schistosomiasis. AB - The present paper reviews the literature to determine whether there are predisposing factors which influence the transmission, prevalence, intensity of infection and morbidity of schistosomiasis in women. The review suggests that: (1) the higher prevalence rates observed in males, in most endemic areas, are not due to sex per se, but to the greater opportunities afforded to males for exposure; (2) cultural and social practices often determine occupational roles and, in some circumstances, these practices may protect women from exposure; (3) when women assume typical 'male' roles, their risk and prevalence of infection increases; (4) in Muslim societies, women's exposure to water is restricted and infection rates are usually lower; (5) morbidity does not appear to be influenced by sex; and (6) the most important impact of schistosomiasis on women is its possible disruption of maternal functions, such as pregnancy, and its role in maternal, infant and child mortality and fetal wastage. Suggestions are also made for expanding existing research and for new studies concerning factors which may influence infection and disease in women. PMID- 8211262 TI - Women and congenital Chagas' disease in Santa Cruz, Bolivia: epidemiological and sociocultural aspects. AB - A total of 910 mothers attending the Percy Boland Maternity Institute in Santa Cruz were investigated. Of these mothers, 9.5% transmitted Chagas' disease to their children. It was observed that the frequency of congenital transmission in the city was influenced by certain socio-cultural factors relating to the mother, such as increased fertility, early age of motherhood and blood transfusions, and also by the movement of migrants from other endemic regions of Bolivia and from rural areas in the same department. It is postulated that the persistence of the disease in the urban setting is due to a second-generation transmission cycle. Comments are made on how regions where Chagas' disease is endemic become risk areas for women migrating from non-endemic regions, as well as on the need to develop an adequate strategy for the control of this non-vectorial form of transmission of Chagas' disease. PMID- 8211263 TI - Gender and tropical diseases: a new research focus. AB - This paper examines the underlying assumptions that have led to a lack of attention to women's health, particularly in developing countries, beyond the context of their reproductive roles. It is argued that the peculiar nature of women' responsibilities both in economic production and within the family, may have a profound impact on the extent to which they are affected by tropical diseases and their responses to disease. It is suggested that the gender relations of health are of considerable significance in explaining the differential consequences of tropical disease on women, men and children. The paper proposes a framework for gender-sensitive research on this topic and suggests some new directions for research. PMID- 8211264 TI - Strategies of influence in medical authorship. AB - The notion of a rhetoric of science argues that scientific writing is not unproblematically neutral and objective, but rather laden with both theory and value and necessarily persuasive. The nature of persuasion within the profession of medicine is studied here through an analysis of rhetorical strategies at work in medical journal articles. (All articles are on the subject of functional headache and appear after 1982 in such journals as the Journal of the American Medical Association, The Lancet, The New England Journal of Medicine and Headache.) The analysis is organized using the Aristotelian categories of invention (the discovery or creation of arguments), arrangement (their organization in the most persuasive order) and style (including such matters as the use of the passive voice and the avoidance of figurative language). The result of the analysis is a comprehensive inventory of strategies medical authors use in order to influence their peers. The inventory provides a vocabulary and a procedure for analysis of medical rhetoric in general; that is, it goes some way to enabling a medical metadiscourse. The analysis further suggests that rhetorical studies, as a discipline, has much to contribute to medicine's project of examining its own assumptions and scrutinizing its own dominant paradigm. Identifying rhetorical strategies at work in medical journals is one way to articulate medical values and to understand them as instruments of action within the profession. PMID- 8211265 TI - Factors influencing self-diagnosis and treatment of perceived helminthic infection in a rural Guatemalan community. AB - Changes in the diagnosis and treatment of helminthic infection were examined during a longitudinal study in a rural community in Guatemala. Self-diagnosis was predominant, with an increase in perceived helminthic infection during an economic crisis within the community. Allium sativum L. and Chenopodium ambrosoides L. were used as anthelmintics, often in conjunction with commercial drugs. During the economic crisis the use of plants as treatment for perceived infection increased whereas use of commercial helminthic medicine decreased. Dietary modifications were observed during periods of perceived infection, but were not consistent in the food items modified or the nature of the modification. Within the community individuals exhibited considerable heterogenity in their approaches to treatment. PMID- 8211266 TI - Cost-effectiveness of neonatal screening for Duchenne muscular dystrophy--how does this compare to existing neonatal screening for metabolic disorders? AB - Costs of screening a series of 18,152 newborn males for Duchenne muscular dystrophy (DMD) in Canada were evaluated. The final aim of neonatal screening for DMD is the avoidance of additional cases in the families identified. Total costs to avoid one case of DMD were estimated at Cdn. $172,000, while the incremental costs were found to be $83,000. Reagent costs, test sensitivity, efficacy of screening and compliance with genetic advice were identified as factors crucial for cost-effectiveness. Costs of neonatal screening for DMD are compared with costs of neonatal screening for inborn metabolic disorders. It is found that the two programmes are similar in costs. Earlier predictions of inordinate costs of screening for DMD are refuted. PMID- 8211267 TI - Organizational predictors of outcomes of long-stay nursing home residents. AB - Analysis of physical function as a measure of nursing home resident outcomes in 10 nursing homes revealed that organizational design variables were important. Results were consistent with contingency theory, which posits that to maximize performance organizational structure should be adjusted to variations in task difficulty and variability. This study revealed that better resident outcomes sometimes are achieved in faster-paced nursing homes when employees are less closely supervised and when the basis for job assignment is clear and consistent. A more hierarchical structure may be effective when workload is heavy. However, when workload and pace are held constant, better outcomes are associated with smaller hierarchies and non-specific job assignment. Implications for management and future research are discussed. PMID- 8211268 TI - The work patterns of lactating women in Madura. AB - Little is known about the work patterns of mildly malnourished lactating women: are they modified to accommodate the demands of lactation? What factors influence their pattern of work during this period of nutritional stress? These questions were addressed using quantitative and qualitative data collected from 36 randomly selected women living in a poor community in Madura, Indonesia. Work patterns of the lactating women and their family members were documented for the first 12 months post-partum. Changes in work activity were analysed within four time periods corresponding to Madurese views on development during infancy: the vulnerable neonatal (birth-40 days), early (6-12 wk) and mid (13-31 wk) stages and the independent late (32-54 wk) stage. Quantitative data suggest that women did adjust work patterns to accommodate the demands of lactation and that these adjustments went beyond the neonatal stage. Mothers curtailed their participation in high- and low-energy income-generating activities, modified their conditions of work to promote maternal-infant proximity and conserved energy while performing specific activities. These patterns were most common through the mid infancy stage. Data are presented that describe how cultural values supporting maternal-infant proximity, intra- and inter-familial work exchanges, season and resources played a role in the type of accommodations mothers were able to make to breast-feed. These data suggest that even in relatively poor environments alterations in work patterns that may be favourable to lactation are possible, particularly when cultural concepts of infancy support such a trade-off. PMID- 8211269 TI - Consensus in medical communication. AB - This paper discusses a survey which was carried out to investigate the types of risks and inconveniences which are normally disclosed by surgeons before operations. By restricting the survey to a specific operation, the Charnley Hip Replacement procedure, greater precision in replies was obtained. The results, however, shed light on both the medical and the legal aspects of informed decision in surgery generally. The survey data was analysed using the concept of neighbourhood consensus [1: Dodd F. J. and Donegan H. A. Proc. of ILIAM 6, pp. 17 29. University of Ulster Press, Ulster, 1989]. PMID- 8211270 TI - Communities, AIDS and geography. PMID- 8211271 TI - Identifying distress among general practitioners: predictors of psychological ill health and job dissatisfaction. AB - This paper attempts to identify sources of job stress and personality factors as predictors of psychological ill-health and job dissatisfaction among a large sample of general practitioners in the United Kingdom. Compared to a normative sample, male doctors exhibit significantly higher levels of anxiety and depression, whereas female doctors compare favourably to the population norms. Job satisfaction levels were significantly lower than when they were measured in 1987, although women were less job dissatisfied than men. The main predictors of lack of mental well-being were the job stressors associated with the 'demands of the job and patients' expectations', 'practice administration and routine medical work', 'role stress' and the use of 'social support' as a coping strategy. PMID- 8211272 TI - The relationship between the cost of community care and the dependency of old people. AB - In this paper the relationship between resource use, costs and dependency is examined for a 'captured population' of old people living in the community but attending day hospital care. Dependency is measured using a Guttman (activities of daily living) based scale. Resource use is assigned by category of dependency and an opportunity cost methodology is used to estimate the cost of care. The results generally confirm that the overall cost of care increases with dependency, though there are exceptions to this trend when each component of care is analysed separately. For instance, not all elements of day hospital provision increase as dependency gets worse, as witnessed by the relatively low provision of paramedical care to old people in the highest category of dependency. The results also confirm that community care is not a cheap option. Once informal care is quantified and valued, the cost rises accordingly. Moreover, if persons living in the community are attending day hospital or have occasional in-patient stays in acute hospitals, costs will rise even more. This is not an argument against community care. Rather, it is to emphasize that while it may be better for some dependent old people to live at home it is not necessarily cheaper. This will come as no surprise to the many carers of old people whose work has rarely been satisfactorily taken into account in comparative analyses of the cost of care. PMID- 8211273 TI - Patient satisfaction with communication in general surgery: problems of measurement and improvement. AB - The research reported here is taken from a pilot inquiry into patient experiences of general surgery provided in National Health Service hospitals. This study sought to identify how the cross section of patients facing general surgery experienced communication and information problems particular to their surgical 'settings', how such discontent is understood or rationalised by them, and consequently how it would be reported to relatives or researchers. Drawing on interviews with patients and surgical staff, the paper explores the range of communication difficulties facing certain types of patient which arise from the hospital setting and the routines and rituals of service providers. While it is concluded that communication should be explored with some reference to disease classification, this should not divert attention from the general context of care to the unique circumstances of patient or surgeon. It is questioned whether patients are always disposed to rationalise their difficulties in terms of 'dissatisfaction' in the way required by survey research. Drawing on interview generated comments by patients and staff, the paper illustrates less obvious validity problems for patient satisfaction studies, and addresses briefly questionnaire design which may account for them. PMID- 8211274 TI - Housing stressors, social support and psychological distress. AB - This paper explores the links between housing stressors, social supports and psychological distress. It was hypothesised that exposure to housing stressors would be significantly related to psychological distress, but that the adverse effects of housing stressors would be moderated by perceptions of social support resources. In other words, the stress/symptom relationship would be attenuated for individuals who believe that they have active and supportive social relationships. The results of a study conducted in the two New Zealand cities of Auckland and Christchurch partially confirmed this hypothesis, indicating that social support plays a role in mitigating the adverse effects of housing stressors. However, this relationship depends on the severity of the housing stressors. Among our respondents, the presence of social support was indeed associated with reduced symptom levels for those exposed to moderate housing stressors. However, among respondents subjected to high levels of housing stressors, social support was not associated with reduced psychological distress, indicating the need for a more specific policy response to the issue of seriously deficient housing. PMID- 8211275 TI - Renal disease and black Americans: selected issues. AB - Black Americans compared with their white counterparts are disproportionately hypertensive and have a greater incidence of end-stage renal disease (ESRD). Renal disease is a frequent end point of accelerated hypertension. The reasons why black Americans have a higher incidence of ESRD relative to white Americans are explored. As transplantation is a preferred mode of treatment for chronically ill ESRD patients, the paper examines some of the reasons why blacks are more reluctant than whites to donate their organs (e.g. kidneys) for transplantation. Although various reasons affect organ donation, altruism is explored as a possible factor that may influence the willingness of blacks to donate their organs. PMID- 8211276 TI - Determinants of regional differences in lung cancer mortality in The Netherlands. AB - Although regional differences in lung cancer mortality are likely to be attributable to regional differences in tobacco smoking, studies in various countries found only weak relationships. This paper aimed at explaining regional differences in lung cancer mortality in the Netherlands. In a first step, clues for the role of smoking were obtained from a detailed description of regional mortality differences. These differences were found to be strongly determined by cohort effects: they vary between birth cohorts, and have been stable for over 30 years. Regional mortality differences reflect a diffusion of the lung cancer epidemic from high-income regions to low-income regions. These findings are suggestive of a relationship with regional differences in trends in cigarette smoking. In a second step, by means of multiple regression analysis, mortality differences in 1980-84 were related to available data on cigarette smoking and two other possible risk factors: work in transport and manufacturing industry, and air contamination. The independent variables referred to the 1970s. Positive associations with various smoking measures were found for women, but for men the associations were weak or non-existent. Mortality differences among men 45-64 years were associated with work in transport and manufacturing industry. Strong associations with air contamination were found for men and women 65 years and older. Additional analysis showed that regional differences in lung cancer among old men were strongly associated with smoking in 1930, i.e. half a century before. Changes in the regional pattern of tobacco consumption between 1930 and 1970 explain why smoking in 1970 is not associated with mortality differences in the 1980s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8211277 TI - Women's satisfaction with maternity health care services in Finland. AB - The purpose of this study was to describe the Finnish maternity health care system and to determine the level of satisfaction in general with maternity health care services and specifically with hospital clinic visits in Helsinki, Finland. Information was collected using both interviews (N = 63) and questionnaires (N = 408). Care during pregnancy takes place in maternity centers, and risk pregnancies are referred to hospital clinics for consultation. The maternity health care system in Finland is regarded internationally as effective and well functioning. In recent years, however, increasingly more prenatal visits have taken place in hospital clinics. This change may lead to a system similar to Great Britain's where a large part of prenatal care takes place in hospital clinics. Although the women in this study are satisfied in general with the content of maternity health care services and regard them necessary for their well-being during pregnancy, data also indicated that women are more satisfied with visits to maternity centers than with visits to hospital clinics. The factors women complained most about in hospital clinic visits, were long waiting times, unsatisfactory doctor-patient communication, the 'assembly-line' routine of the clinic, and seeing a different doctor at each visit. The lack of social and psychological support involved in the care given at hospital clinics was also evident. In planning and evaluating maternity health care, it is important to consider women's views and experiences. PMID- 8211278 TI - The use of preventive health care services: carrier testing for the genetic disorder haemophilia. AB - A retrospective study was performed to explore carrier testing among women who were possible or obligate carriers of the haemophilia gene. Knowledge of the possibility of carrier testing and use of carrier testing were studied separately. In our exploration we were guided by the diffusion theory and the Health Belief Model. Logistic regression analysis showed that four factors were statistically significant related to knowledge of carrier testing: information via mass media, a haemophilic relative in the nuclear family rather than in the extended family, medical severity of haemophilia, and information from the patients' organization. For those women acquainted with carrier testing two of the four factors just mentioned were significantly related to the utilization of carrier testing i.e. having a haemophilic relative in the nuclear family and the medical severity of the haemophilia. In addition the following factors were associated: attitude towards abortion because of haemophilia, educational level, and marital status. Notwithstanding the prominent function of the mass media and the patients' organization, the respondents themselves stated that relatives, especially parents and sisters, were the most important source of information on genetic counselling and carrier testing. PMID- 8211279 TI - Maternal perceptions of pneumonia and pneumonia signs in Pakistani children. AB - Fifty mothers of children attending a hospital outpatient clinic with non-severe pneumonia (fast breathing but no chest indrawing) were interviewed in depth. Maternal perceptions and practices with clinical significance were documented. Results showed that most mothers initially tried "heat-producing" home remedies designed to counter the "coldness" of the disease, allowed only 2 days for any particular allopathic medicine to work, and did not go to the same practitioner twice. When mothers were asked what had alarmed them enough to come to the hospital, the symptoms named most frequently were persistent severe cough and high fever, inability to sleep and excessive crying. Fast breathing was spontaneously mentioned by only a few, although when questioned, 32/50 said that they had noticed it. The mothers who had prior experience with child pneumonia were more likely to notice fast breathing and also came to the hospital earlier than those who were inexperienced. Relatively higher levels of maternal education and income were suggestively associated with bringing a female child rather than a male child for pneumonia treatment. Fewer than half of the mothers knew where air goes when a person breathes in and where the lungs are located. Most held treatment preferences at odds with the protocols proposed for the national ARI program currently being initiated in Pakistan, e.g. they said that a doctor should use a stethoscope, should prescribe suspensions rather than tablets and should give injections. This study provides baseline data on attitudes and behaviors that can either be built on in that program or addressed through public education campaigns. PMID- 8211280 TI - Sexual practices and attitudes of street youth in Belo Horizonte, Brazil. Street Youth Study Group. AB - Street youth are at risk of HIV infection worldwide. To develop effective prevention strategies, information about the meanings and functions of sexual activity for street youth is needed. In this paper, data from structured questionnaires, focus group discussions, in-depth interviews and field observations are used to build up a picture of the sexual culture of 9-to-18-year olds living and/or working on the streets of a large Brazilian city. The findings reveal that these children and adolescents engage in sexual behavior that puts them at risk of sexually transmitted diseases, including HIV/AIDS, and reinforce that sex is a multi-determined and entrenched behavior in this population. Interventions must take into account the fact that for street youth, sex is used as a means of ensuring survival, seeking comfort, finding pleasure, and dealing with psychological issues that arise during adolescence. PMID- 8211281 TI - Me' winik: discovery of the biomedical equivalence for a Maya ethnomedical syndrome. AB - Investigation of the correspondence of ethnomedical illness syndromes and biomedical disease classification has led to the identification of a high prevalence of gallbladder disease among the Tzeltal and Tzotzil Maya populations of Highland Chiapas. This condition, known to demonstrate exceptionally high rates among North American Indians, has not previously been described among the Highland Maya. The failure to recognize this serious health problem has been due primarily to cultural differences in understanding the anatomy and difficulties arising from communication of symptomatology. A focus on the interface of ethnomedicine and biomedicine is shown to have significance from both theoretical and applied perspectives. PMID- 8211282 TI - Focus group interviews about AIDS in Rakai District of Uganda. AB - Focus group interviews about AIDS were held in Rakai district, Uganda during early 1990 with groups from various sections of the community. It was found that the knowledge of AIDS symptoms and its transmission were widespread. Attitudes regarding many aspects of sexual behavior, AIDS patients, condoms, injections, hospital treatment, sexually transmitted diseases and an AIDS cure were investigated. We found that most people no longer fear casual contact with AIDS patients but they blame spouses of people with AIDS for spreading the infection. Condoms are generally not trusted. Many people feel that condoms cannot prevent transmission of the AIDS virus and some fear that they may get torn and cause complications in women. Most people now do not like injections for treatment and when necessary, prefer disposable needles and syringes. Hospital treatment for AIDS patients is not trusted very much, and many people believe that AIDS patients are intentionally killed off by doctors. Sexual behavior was extensively discussed and it was found that there is generally a reduced level of multiple sexual partners. The reduction is more marked in rural areas but the urban areas are still having higher levels of multiple sexual partners. PMID- 8211283 TI - Family planning practice in central Sudan. AB - Community and hospital based studies were conducted to assess the major factors related to the practice of family planning during 1989 and 1990 in Central Sudan. The mothers of 1592 births in the community and 1357 births in the hospital were interviewed by trained study workers. Prevalence of contraceptive use prior to current pregnancy was 13.0% and knowledge of a family planning method was 43.0% among hospital women and 51.0% among community women. The major predictors of use of a family planning method were parity, socioeconomic status, knowledge of source of service and maternal age. The average completed family size was 7.7 children and with the exception of a lengthy breast feeding duration, the factors examined favored a high fertility. Women preferred and apparently practiced behaviors conducive to spacing rather than limiting the number of their children. The results between the hospital, the community, and the Sudan Demographic and Health Survey 1989/1990 were consistent suggesting a minimal effect of selection bias and increasing the validity of these findings. Accessible and available family planning services coupled with wider information on family planning through health personnel and the media are needed. In particular, special efforts should be made to reach women of low socioeconomic status. PMID- 8211284 TI - Constructing generaliseable socio-economic indices. PMID- 8211285 TI - A medical geographical anniversary. AB - It is now 200 years since L. L. Finke wrote his treatise on a global medical geography, Versuch einer allgemeinen medicinisch-praktischen Geographie. It was both the most extensive book in substantive content, and the most detailed in conceptual discussion on medical geography written to that point. Although it is one of the foundation pieces of medical geography, modern day practitioners seldom refer to Finke's work. There are two main reasons for this: with the exception of two passages, the work has never been translated from the original German, and many contemporary medical geographers believe that the field only developed in the mid-twentieth century. This paper's purpose is to demonstrate that this last point is unfounded and that recognition of Finke's seminal contribution is long over-due. On the 200th anniversary of the publication of An Attempt at a General Medical-Practical Geography Finke's great achievement is honoured. PMID- 8211286 TI - Space in its place: developing the link in medical geography. AB - This paper argues that a re-examination of the interrelationship between constructs of place and space is crucial to geography's involvement in the broader endeavour of health research. Place has re-emerged as nexus of ascribed meaning within contemporary social theory. Places, however, are related in space, by distance or proximity. The distinction needs to be made between this orthodox (geometric) view of space and two types of social space: the (experienced) space described by humanist geographers; and the more recent (socio-spatial) conceptualization which is both experienced and (re)produced by societal structures and advocated by social theorists in geography. We argue that advancing a recursive understanding of space and place is an appropriate direction in medical geography. This direction will include both an understanding of the ways in which space shapes the character of places and how the particularities of places resist or set in motion (orthodox) spatial processes. Illustrations are drawn from studies of mental illness and mental health care and primary health care in a remote area of New Zealand. PMID- 8211287 TI - On the validity of language: speaking, knowing and understanding in medical geography. AB - This essay examines methodological problems concerning the conceptualization and operationalization of phenomena central to medical geography. Its main argument is that qualitative research can be strengthened if the differences between instrumental and apparent validity are better understood than the current research in medical geography suggests. Its premise is that our definitions of key terms and concepts must be reinforced throughout the design of research should our knowledge and understanding be enhanced. In doing so, the paper aims to move the methodological debate beyond the simple dichotomies of quantitative vs qualitative approaches and logical positivism vs phenomenology. Instead, the argument is couched in a postmodernist hermeneutic sense which questions the validity of one discourse of investigation over another. The paper begins by discussing methods used in conceptualizing and operationalizing variables in quantitative and qualitative research design. Examples derive from concepts central to a geography of health-care behavior and well-being. The latter half of the essay shows the uses and misuses of validity studies in selected health services research and the current debate on national health insurance. PMID- 8211288 TI - Do places matter? A multi-level analysis of regional variations in health-related behaviour in Britain. AB - A number of commentators have argued that there is a distinctive geography of health-related behaviour. Behaviour has to be understood not only in terms of individual characteristics, but also in relation to local cultures. Places matter, and the context in which behaviour takes place is crucial for understanding and policy. Previous empirical research has been unable to operationalize these ideas and take simultaneous account of both individual compositional and aggregate contextual factors. The present paper addresses this shortcoming through a multi-level analysis of smoking and drinking behaviours recorded in a large-scale national survey. It suggests that place, expressed as regional differences, may be less important than previously implied. PMID- 8211289 TI - Ambiocontrol as a primary factor of health. AB - This paper is based upon the results of two research projects that took place in very dissimilar places and contexts, at different situations in the epidemiological transition process, but lead to some important common conclusions. In both studies, a geo-systemic or socio-spatial classificatory model was first constructed, comprising a series of environmental (independent) variables. Second, this model was used to reveal, measure, and try to explain the health disparities existing in the area under study, as measured by certain health indicators (dependent variables). Two socio-spatial models were constructed. The first used 26 environmental variables, measured in the 78 municipios of Puerto Rico. The dependent variables were mortality rates. The second employed 28 environmental variables, measured in the 32 community health department territories (DSCs) of Quebec. The dependent variables were physical and mental health indices. The most significant common conclusion of these studies is that the socio-economic level per se, or its classical principal defining elements (income, education level) are not the main determinants of the observed health disparities. A certain stability in the physical and social environment, the person's sense of understanding of his environment and of control over the course and setting of his own life (what is called ambiocontrol) that is induced by this stability appear to be the most important determinants of health. On the other hand, centrality, complexity and instability of the environment are the most pathogenic characteristics of the milieu. PMID- 8211290 TI - Maternal mortality in Africa: 1980-87. AB - African women of reproductive age have the highest death risk from maternal causes of any women in the world. The lifetime chance of maternal death is 1 in 21 in Africa as compared to 1 in 54 in Asia, which ranks second. Using published data, this paper examines the level and correlates of maternal mortality ratio (MMR) in Africa. The data indicates that MMR greatly differs among the countries of Africa. High MMR is found in most countries of sub-Saharan Africa, while countries of Northern Africa are characterized by relatively low maternal death. Reasons for high MMR in sub-Saharan Africa are explored in detail. Analysis using multiple regression suggests that the MMR in Africa is strongly influenced by population size, crude birth rate (CBR), crude death rate (CDR), calorie supply as a percentage of requirements, access to safe water, and percentage of urban population. Some cultural and behavioral factors, such as female circumcision and infibulation, are also associated with a high MMR. Future programs aimed at reducing the maternal mortality in African countries may benefit from the findings of this study. PMID- 8211291 TI - Cancer clusters: the importance of monitoring multiple geographic scales. AB - Analysis of cancer incidence data at a variety of geographic scales provides surveillance information that can allay fears of the general public, prevent costly and unwarranted epidemiologic studies driven by political pressures, and target appropriate cases for further investigation. We systematically examined New Jersey Cancer Registry data (1979-1985) for childhood and young adult (0-24 years) cancers at multiple geographic scales--at the state level, then by degree of urbanization, county boundaries, and minor civil divisions. The state had increased rates for some cancers when compared to four other SEER (Surveillance, Epidemiology and End Results) states. No meaningful patterns at either the most urban/suburban/most rural scales or at the county level of analysis were found. At the minor civil division level, the Ederer, Myers and Mantel method found evidence of clustering of pediatric and young adult cases statewide. Stratification of cases by race yielded even stronger findings and indicated that whites had clustering of cases for several cancer types. In-depth analysis of individual cases yielded hypotheses for investigating identified clusters. PMID- 8211292 TI - (Over)eating success: the health consequences of the restoration of capitalism in rural China. AB - This paper reviews and evaluates some of the changes that have occurred in the Chinese health care system during the reform era associated with Deng Xiaoping (1978-1993). The reforms have helped to enrich the long suffering peasants in the Chinese countryside, and in many areas the peasants have experienced a significant improvement in the quality of their lives, including greater access to health care facilities, and better diets. The paper also considers some of the potentially negative side effects of the reform era, including the increasing income inequality between urban and rural areas; the commodification of Chinese medicine; declining access to health care for peasants in the poorest regions; and a concern about the changing patterns of diet and nutrition in the newly enriched parts of the Chinese countryside. PMID- 8211293 TI - Lymphoma, multiple myeloma and leukaemia among French farmers in relation to pesticide exposure. AB - Lymphoma, multiple myeloma and leukaemia mortality among French male farmers and farm laborers (1984-1986) has been studied geographically. In each geographical area (89 "departements") exposure to pesticides in arable land has been characterized by an index taking into account different practices in the treatment of various crops as well as an estimate of the time per farmer spent cultivating each crop in 1970. The farmers population as a whole presented an increased mortality for multiple myeloma (SMR = 1.59, 95% CI = 1.32-1.89) and leukaemia (SMR = 1.33, 95% CI = 1.19-1.49) but not for lymphoma (SMR = 1.09, 95%, CI = 0.94-1.26). Using Poisson regression, leukaemia mortality appeared significantly linked to the pesticide exposure index (P = 0.04), after adjustment of farmers' economic status and a linear geographical gradient, whereas no significant relationship was found for lymphoma or multiple myeloma. This result reinforces a similar link reported from a previous French geographical study conducted at a smaller scale within a region. PMID- 8211294 TI - Epidemiological transition and geographical discontinuities: the case of cardiovascular mortality in French Polynesia. AB - The need to maintain the unity of geography justifies the use of every possible approach to the study of spatial discontinuities. The geography of health can be enriched by studying and applying routine methods of regional geography. To achieve this aim, the use of epidemiological transition theory, involving its transposition from the domain of time to space, is proposed. This requires careful analysis of sources of data not commonly used in geography and emphasizes links between health, environment and development. French Polynesia constitutes a prime study area for such an approach, especially because of its multiple contrasts in geographic scale and levels of development between the different archipelagoes and even within individual islands. To demonstrate the utility of this approach, cardiovascular mortality is studied at different geographic scales. Results are displayed as health spatiograms which show the discontinuities of human geography in French Polynesia at different scales. The results appear to constitute synthetic indicators of socio-spatial disparities and permit the geography of health to contribute not only to the measurement of regional health conditions but also to the matters of global human geography. PMID- 8211295 TI - Modelling psychosocial effects of exposure to solid waste facilities. AB - A parallel case study design was used to investigate psychosocial effects in populations exposed to solid waste facilities. Psychosocial effects were defined as a complex of distress, dysfunction and disability, manifested in a range of psychological, social and behavioural outcomes, as a consequence of actual or perceived environmental contamination. This paper presents the results of logistic regression analyses designed to identify determinants of psychosocial effects of exposure. The data come from an epidemiologic survey of residents (N = 696) living within a prescribed radius from each of three solid waste facilities in southern Ontario. The analytical model has three main components: external variables (e.g. individual and exposure-related variables); mediating variables (e.g. social network membership and involvement, general health status measures); and outcome variables (e.g. concern, effects and actions). Results for a series of site specific analyses show that outcome measures can be successfully explained by a combination of external and mediating factors. In general, variables from each of the three main components enter the concern-related models while the action models are clearly dominated by social network variables. Analyses using data from all three sites indicate the explanatory power of site related characteristics. However, given the number and diversity of variables in the models, there is no support for a simple cause and effect relationship. The implication is that strategies aimed to address and alleviate psychosocial effects need to be specific to the characteristics of the populations in particular settings. PMID- 8211296 TI - Worrying about waste: living close to solid waste disposal facilities in southern Ontario. AB - As a complement to an epidemiological survey, depth interviews were used to discover the individual level impacts of living close to waste disposal facilities in southern Ontario. The paper begins by describing the nature of the sites and reporting some of the survey findings, which the depth interviews explored. Sample selection and data analysis methods are described. A by-code analysis of the material is presented, emphasizing both within- and between-site differences in type and concern (or impact). Concern varied according to type of exposure and site context. The paper ends with a discussion which relates the study's findings on non-toxic facilities to other research on psychosocial effects, lay reasoning and risk perceptions and assessments. PMID- 8211297 TI - On the use of socio-demographic indicators in local health planning: a Canadian non-metropolitan perspective. AB - This paper argues that the use of socio-demographic indicators to represent actual or potential demand for mental health services needs to be informed by knowledge of local settlement conditions and trends. Following a selective review of the literature on the use of socio-demographic indicators in mental health care planning and on the spatial ecology of mental illness, a case study of a non metropolitan jurisdiction in southern Ontario, Canada is presented. The results of a regression-based analysis reveal a strong association between the socio demographic composition of populations and hospitalization rates for mental illness. The pattern of correlates appears to be underlain by residential location processes that 'filter' populations on the basis of age and socio economic status. It is concluded that, in the absence of this knowledge of local social geography, applications of indicators methodologies run the risk of being 'black boxes'. PMID- 8211298 TI - Avoidable mortality in Quebec and its regions. AB - Avoidable mortality has been proposed as an outcome measure of health services and our aim, in this study, is to trace its general features and regional variations in Quebec. For that purpose, comparisons are established between two time periods (1969-73 and 1982-90) and with several countries. Furthermore, regional SMRs (for the period 1982-90) are submitted to the Gail heterogeneity test and introduced in a stepwise regression with variables describing health services, socio-economic context and prevalence or incidence of related diseases. An analysis of proportional mortality is carried out in the two northern regions of Kativik and Baie-James. Avoidable mortality has dropped substantially in Quebec, except in the case of asthma, and now displays excellent scores at the international level. Only three causes of death show significant regional variations: tuberculosis, hypertensive and cerebrovascular diseases and perinatal mortality. These variations are mainly associated with socio-economic factors but also with health services. Furthermore, the highest rates of avoidable death have been observed in Gaspesie, Saguenay/Lac St-Jean and in the two northern regions. These results are discussed through information already available on health services in Quebec. PMID- 8211299 TI - Variation in duration of hospital stay between hospitals and between doctors within hospitals. AB - Whether one examines the average length of hospital stay at the level of geographic areas, at the level of hospitals, or at the level of doctors, length of-stay figures are known to vary widely. Even for hospital admissions for comparable surgical procedures among comparable groups of patients, significant length-of-stay variations have been reported. As is the case for variations in the occurrence of common surgical procedures, the overall conclusion is that large variations in duration of hospital stay associated with these common surgical procedures are the rule rather than the exception. The objective of the study is to examine whether variations in hospital medical practice, indicated by the duration of hospital stay in this study, can be reduced to differences in practice style between individual doctors within the same institutional setting or to differences in practice style between groups of doctors within the same institutional setting. The latter is assumed to be the combined effect of restrictions on the (hospital) supply side and the predilection of doctors to conform to the practice of immediate colleagues. It was found out that the variation in length of hospital stay, adjusted for patient case-mix, within hospitals is much smaller than the length-of-stay variation between different hospitals. The within hospital variation between (partnership of) doctors is in most of the cases statistically insignificant. Doctors working in more than one hospital on average choose a length of stay close to the average length of stay prevailing in the different hospitals. PMID- 8211300 TI - The biological vision: triumphs and hazards. PMID- 8211301 TI - State authority, medical dominance, and trends in the regulation of the health professions: the Ontario case. AB - The relationships amongst the health professions and between them and the state are rapidly changing. I argue that analysis of these relationships has to take into consideration: the fact that medicine played an intermediary role (through medical dominance in health care) between the state and the other health occupations; the permeability of the boundaries of the state and the professions; and the dual nature of professional organizations (as sites of intra-occupational conflict and as possible vehicles of extra-occupational control). In Ontario the medical profession partially 'mediated' the relationships between 'non-physician' health occupations and the state through medical control over other health care occupations. National/provincial health insurance brought the state into the health care system as an actor and forced a reconsideration of its relationships with medicine and with the other health care occupations. The state came to be directly involved in 'rationalizing' health care. This involvement meant curbing the power of medicine and modifying the relationships between medicine and the para-medical occupations. State influence is partly constructed through a particular kind of professional organization, namely, the professional College. These changing relationships are illustrated by historical and recent developments regarding medicine, nursing and chiropractic in Ontario. PMID- 8211302 TI - Explorations in consultation of the public and health professionals on priority setting in an inner London health district. AB - The methodology for eliciting the public's priorities for health services is in its infancy. This paper presents the results from a series of exploratory exercises on priorities in City and Hackney. The authors surveyed the opinions of members of community groups and tenants' associations, and compared their responses with those of a random sample of the public as well as general practitioners, consultants and public health doctors. This revealed some disagreement on priorities between these groups. The public, in consistency with the results from other studies, prioritised perceived life saving technologies as high, in contrast to community services and services for people with mental illnesses, which they prioritised as medium to low, in contrast to all the samples of doctors; the public also prioritised health education and family planning as fairly low, as did the GPs and consultants, in contrast to the public health doctors who prioritised them as high. Before DHAs embark on these studies as part of priority setting, they must answer the question: "what will they do if they disagree with the results?" PMID- 8211303 TI - African women's control over their sexuality in an era of AIDS. A study of the Yoruba of Nigeria. AB - Very limited knowledge is available about African women's control over their sexual relations with husbands or other stable partners in situations where there is a high risk of STDs and HIV/AIDS. Such control must be seen as encompassing women's control over their sexuality and reproduction as well as the broader areas over which they can make decisions. The paper examines other research findings in sub-Saharan Africa, and then reports a study carried out by survey and anthropological methodologies among the Yoruba people in Ado-Ekiti, a town in southwestern Nigeria. Because the AIDS epidemic is still at an early stage in Nigeria and because of the relation of STD infection to HIV-transmission, as well as the probability that the behaviour developed for limiting STD transmission will subsequently be employed to limit HIV transmission, the study focused on STDs. Yoruba women have a considerable ability to refuse sexual relations for a limited time, and they are placed at greater risk of STD infection by their ignorance of whether their partner is infected than by a lack of ability to control the situation when STDs have been identified. This ability may be more limited in the case of AIDS because of its longer duration. PMID- 8211304 TI - Ante-natal screening: what constitutes 'benefit'? AB - This paper discusses the application of economic appraisal in pre-natal screening. In particular it examines the way in which economists to date have attempted to measure and value the benefits of pre-natal screening. The authors argue that there are problems with existing approaches particularly in terms of the nature of women's utility functions and which arguments are present in these utility functions. They suggest that policy makers are unlikely to take full account of the results of such analyses until economists better attempt to reflect measures of what women want from pre-natal screening. PMID- 8211305 TI - MMPI profiles of male and female migraine sufferers. AB - Among a sample of 40 severe migraine sufferers, males and females displayed common personality profiles. Both sexes exhibit heightened scores on those MMPI clinical scales associated with neuroticism (hypochondriasis, depression and hysteria). Female migraine sufferers were further characterised by elevated scores on the primary scales constituting the psychotic tetrad (paranoia, psychaesthenia, schizophrenia, and hypomania). Migraine females appeared to differ from male patients with respect to a dimension associated with sex-role conformity (loaded on the L-scale and masculinity-femininity). The implication of these results are considered. PMID- 8211306 TI - The effect of a warning about putative adverse events on drug prescribing in general practice. AB - Many studies have looked at factors influencing doctors' prescribing. None have done this during a time when prescribers have been just made aware of potential serious adverse events that might be caused by a commonly prescribed medication. A controversy over the safety of Fenoterol (Boehringer Ingelheim) in 1989 provided an opportunity for such a study in general practice. Practitioners were exposed to conflicting and changing views from authoritative sources, patient concerns raised by the coverage of the issue in the news media, and a need to maintain patients on effective therapy. The study demonstrated that the majority of general practitioners would act promptly and conservatively when faced with uncertainty about the safety of the medication they prescribed. PMID- 8211307 TI - Social disintegration and the spread of AIDS--II. Meltdown of sociogeographic structure in urban minority neighborhoods. AB - An elementary model of sociogeographic network structure in an urban minority community suggests externally applied stress, particularly that which triggers frequent individual or family moves of increasing distance, may cause a sudden 'phase change' resulting in disconnection of previously integrated subgroups from the community. Such 'community meltdown' would seriously disrupt mechanisms for social control, economic opportunity and socialization of youth, while intensifying substance abuse and indiscriminate and frequent sexual activity, particularly among the very young. 'Phase change' of this nature would seem to preclude success of programs to control spread of HIV infection, particularly in heterosexual populations. The possibility is explored that programs of 'community recrystalization' in disintegrated urban area might likewise need to exceed some threshold of investment and organizing activity before becoming effective. However, if supported to levels above threshold, this work implies such programs might have very great impact in a very short time. The possibility of interaction between behavioral pathologies resulting from the initial meltdown and further consequent deterioration in sociogeographic network structure leads to speculation that the threshold for recrystalization may become significantly and progressively greater than for meltdown. Implications of these matters for diffusion of HIV into the general population are discussed. PMID- 8211308 TI - Essential and non-essential drugs marketed by the 20 largest European pharmaceutical companies in developing countries. AB - This study estimates the proportion of essential drugs out of all drugs offered for sale in six regions of the developing world by the 20 largest European pharmaceutical companies. The total number of drugs offered for sale by the 20 companies is estimated from citations in the most important drug compendia in each region for 1988 and 1989. Essential drugs are defined as drugs listed on the 1988 version of the World Health Organization's (WHO) essential drugs list or equivalent to WHO essential drugs. Only 482, or 16% of a total of 3021 cited drugs were essential drugs or equivalent to an essential drug. The proportion for each company ranged from a low of 5.4% to a maximum of 39.0%. A high proportion, 41.7%, of the 2539 non-essential drugs cited in the compendia contained two or more active ingredients, compared to only 9.5% of the essential drugs. The results indicate that European pharmaceutical companies have yet to focus their drug marketing efforts in developing countries on the essential drugs recommended by the WHO. The ethical responsibility of the pharmaceutical companies is discussed, particularly in respect to their sales on the private market. PMID- 8211309 TI - Physical health status at 36 years in a British national birth cohort. AB - In a nationally representative British sample of over 3000 men and women aged 36 years, those in the best or worst of health were identified on the basis of measured blood pressure, lung function and body weight, self reported health problems and disability, and recent hospital admission. Serious illness in earlier life was strongly predictive of current adult health status. Even after adjusting for this and for current social circumstances and health related behaviour, those who came from poorer family backgrounds or were least well educated did not have an equal chance of being in the best of health at 36 years. Living in adverse social circumstances in adult life increased the risk of having the worst health. The analysis suggests that a number of pathways link childhood experiences to adult health and shows the need for a lifetime research perspective on health. PMID- 8211310 TI - Hispanic Americans and the state mental hospitals in Texas: ethnic parity as a latent function of a fiscal incentive policy. AB - This paper examines patterns of utilization of the state mental hospitals in Texas by Hispanics compared to Anglos over a 5-year period from FY 1984 to FY 1988. Historically, Hispanics have been underrepresented in public mental health client populations in the United States. In the mid-1980s in Texas, the ethnic gap in use of psychiatric facilities was expected to widen as Hispanic population growth outpaced the capacity of the public system to provide accessible mental health services for persons with serious and persistent psychiatric illnesses. But in the inpatient sector, the gap narrowed significantly in the second half of the decade, due to a policy-driven sharp reduction in the overall census of the state mental hospitals. A fiscal incentive program to stimulate the development of community-based mental health services had a markedly different effect on subsequent inpatient utilization by Anglos compared to Hispanics, most notably in counties that were less urban and less affluent and counties with a relatively high proportion of Hispanic residents. The context and mixed implications of these developments are explored. PMID- 8211311 TI - Problems and prospects for health sector links in the southern African region: the role of South Africa. AB - Recent political developments in South Africa provide many opportunities for the development and extension of health sector links in the Southern African region and the possibility to move away from past hostilities towards a constructive future. The need to address health issues at an inter-governmental level is becoming more urgent as poverty, drought and homelessness take their toll on the health of the region's population. This paper examines the prospects for and problems with regional integration in the health sector. It begins by outlining the historical context of regional health sector links and by discussing crucial issues that have to be addressed in relation to future regional activities. It is suggested that future regional co-operation should be based on a new approach to regional security which seeks to overcome adverse relationships, to encourage collective action and responsibility, non-interference in domestic affairs and peaceful resolution of disputes. The second part of the paper examines areas in the health sector that would benefit from co-operation. These include disease control, nutrition, medicines, health services, health personnel and research and development. Potential problems related to health sector links are explored and possible mechanisms for regional integration in the health sector are briefly considered. PMID- 8211312 TI - Reasoning about childhood nutritional deficiencies by mothers in rural India: a cognitive analysis. AB - This study examines reasoning about the cause and treatment of three types of childhood protein energy malnutrition (PEM) by 108 mothers in rural South India. The mothers were interviewed and their explanations of the childhood nutritional problems were verbally recorded, transcribed and then analyzed using cognitive methods of analysis. The results indicated that knowledge and practices associated with traditional systems of Indian medicine prevalent in rural areas greatly influenced the mothers' reasoning. Their explanations were shown to have story-like structures, with sequences of events linked by strong causal explanations. Mothers with higher levels of formal education showed greater verbal use of concepts related to biomedical theories of nutritional disorders. However, their interpretations of these concepts were still based on the traditional theory. The study revealed both positive and negative aspects of traditional knowledge and beliefs for adequate child nutrition and health. The development of improved instructional strategies for nutrition and health education in relation to knowledge organization is discussed in the context of rural India. PMID- 8211313 TI - Ethics are local: engaging cross-cultural variation in the ethics for clinical research. PMID- 8211314 TI - Family preservation under attack. PMID- 8211315 TI - Alcohol and other drug abuse among social work colleagues and their families: impact on practice. AB - This article presents data from a 1987 random sample survey mailed to the membership of the New York City chapter of the National Association of Social Workers. The purpose of the study was to determine the prevalence of alcohol and other drug problems as perceived by social workers among their colleagues and their family members and friends. Forty-three percent of the 198 respondents said that they had known at least one social worker who had a problem with alcohol or other drugs. The large number of social workers with close personal involvement with substance abuse was significant: 60 percent had close friends or family members with a problem, 39 percent had a nuclear family member with a problem, and 11 percent were adult children of alcoholics. The latter group reported a significantly higher impact on job functioning than did the other groups. Implications of these findings and recommendations for dealing with them are discussed. PMID- 8211316 TI - In defense of long-term treatment: on the vanishing holding environment. AB - There are compelling similarities in the caregiving functions of good clinicians and good parents. Both clinicians and parents function best in a supportive environment. Yet many clinicians do not feel supported. They are under relentless pressure to find ever-briefer forms of treatment for all individuals, regardless of the individual's symptoms or circumstances. This pressure is especially distressing for the clinical social worker who, by tradition, has provided therapeutic services for the most-troubled individuals. This article is intended as a supportive gesture for the clinician who is struggling with questions about long-term treatment. Health care trends and contraindications for short-term therapy are addressed. A clinical case is presented. PMID- 8211317 TI - Improving the lives of home care workers: a partnership of social work and labor. AB - A school of social work with an occupational program specialization entered into an agreement with one of the largest trade unions in New York City to do a social and health services needs assessment for the union's newest members: home care workers. The vast majority of these home attendants are low-income African American and Latina women who care for frail aged and disabled Medicaid recipients to prevent nursing home placement. Structured interviews with a sample of 400 union members indicated a need for better health care coverage, especially for stress-related illnesses, along with personal social services to assist with housing, debt, child care, and family issues. The union used this independent university data in its subsequent collective bargaining and won expanded benefits for its members based on demonstrated need. The school then established a union funded member assistance program to institutionalize ongoing support for these members. In the end, action research helped to create both social services and social change; low-income women of color have gained tangible new benefits; and social work's important ties to organized labor have been strengthened. PMID- 8211318 TI - Childhood risk factors in dually diagnosed homeless adults. AB - Although the negative long-term effects of specific childhood risk factors- sexual and physical abuse, parental mental illness and substance abuse, and out of-home placement--have been recognized, most studies have focused on just one of these risks. This article examines the prevalence of these five childhood risk factors among dually diagnosed (mentally ill and substance abusing) homeless adults in rehabilitation programs. It further assesses the impact of each risk factor individually and in combinations of two on the social functioning skills and rehabilitation progress of these multiply disadvantaged clients. PMID- 8211319 TI - Hypnosis--a neglected tool for client empowerment. AB - Clinical hypnosis is a valuable treatment modality that deserves to be more widely known and used by social workers. The author presents an overview of this growing clinical specialty, distinguishing between directive, Ericksonian, and permissive hypnosis. The latter, which is the most common style in use today, is based on a clear contract in which a hypnotherapist helps a client develop and use his or her own hypnotic abilities toward therapeutic goals. Characteristics of a hypnotic trance and the differing capacities of individuals in trance are presented. The article describes how permissive hypnosis is used in practice and identifies the types of clients for whom it is suitable. The author stresses the consistency of modern clinical hypnosis with social work aims and values. PMID- 8211320 TI - Cocaine treatment and outcome. AB - This article describes the dimensions of the current cocaine problem in the United States, drug treatment models, and cocaine treatment effectiveness and outcome. Research on the effectiveness of specific drug treatments, including women-sensitive services, is analyzed. The recommended treatment approaches incorporate a variety of rehabilitative services (for example, housing, education, vocational training, medical services, and child care) and call for social workers to improve linkages with treatment programs and to facilitate referrals. The emerging evidence on treatment models and drug treatment effectiveness can guide social workers in better assisting their clientele by incorporating social services that encourage the development of new and rewarding lifestyles to compete with drug-using activities. PMID- 8211321 TI - Hyperlipidemia in children. AB - Advances toward improving cardiovascular health of tomorrow's adults lie both in acknowledging that the pathogenesis of atherosclerosis begins in childhood and in considering the influence of environmental factors on genetic endowment of risk. Based on current understanding of lipoprotein transport processes, an array of genetic disorders with various degrees of atherogenicity can be classified according to the predominant lipoprotein density class, as represented by a standard lipid profile, and then further defined by assaying apolipoproteins and their receptors, lipoprotein transport enzymes, or the respective variant genes. Alternatively, a simple and potentially cost-effective representation of multifactorial influences on lipid transport is provided by an assessment of apolipoprotein particle composition using serial immunologic precipitation of apolipoproteins while on their intact plasma lipoproteins. A comprehensive intervention strategy can be based on identification of inherited risk and the effects of nongenetic factors, which include dietary excess, inactivity, disease states, and medications. PMID- 8211322 TI - Systemic lidocaine therapy for poststroke pain. AB - Poststroke pain syndrome is commonly regarded as an intractable disease. We describe four patients who responded to an intravenous lidocaine infusion for relief of central pain after a stroke. The infusion was administered over a 48 hour period after an initial bolus of 50 to 100 mg intravenously over 40 to 120 seconds. Pain intensity and pain relief were measured by visual analog and numeric scales. All patients reported some relief within the first 12 hours of infusion. All patients were subsequently given a trial of mexiletine, an oral congener of lidocaine. Two have continued taking the drug and report excellent relief at 12 months' follow-up; the other two had side effects that precluded further use of the drug. We conclude that lidocaine can reduce poststroke pain, and we propose a treatment algorithm based on our experience with 40 additional patients treated for other neuropathic pain states. PMID- 8211323 TI - Clinical presentation of Paget's disease of the bone in older patients. AB - To determine the clinical presentation and manifestations of Paget's disease of the bone in patients older than 60 years, we reviewed the cases of 56 patients attending a bone clinic. Pain was the presenting symptom in 34 cases. It was attributed to the disease process in 21 cases, to osteoarthritis in 11, to trigeminal neuralgia in 1, and to osteosarcoma in 1. Other clinical manifestations included deformities (15 cases), diminished mobility and unsteady gait (9), hearing impairment (7), lethargy (4), diminished vision (3), cognitive deficit (3), sense of warmth in limbs (2), ill-fitting dentures (1), and fracture (1). We concluded that in patients older than 60 years, Paget's disease of the bone may present itself in a variety of ways, some of which may be mistakenly attributed to the "aging process" or some other disease. Furthermore, in this age group, osteoarthritis is responsible for the pain experienced by about one third of symptomatic patients. PMID- 8211324 TI - Physiologic amputation prevents myoglobinuria from lower extremity myonecrosis. AB - Myoglobinuria secondary to myonecrosis is a proven cause of renal failure, especially in critically ill patients. Physiologic amputation or cryoamputation has been used at our institution for the past two decades as a safe and effective treatment for lower extremity infection, intractable rest pain, and irreversible myonecrosis. We retrospectively studied five critically ill patients with myonecrosis of lower extremities associated with myoglobinuria. The etiology of myonecrosis included preexisting peripheral vascular disease or crush injury to the lower extremities. It was determined that all five patients were too ill to undergo emergency amputation. Myoglobinuria was documented in all five patients and cleared within 24 hours of physiologic amputation in four patients. All five patients had elevated creatine phosphokinase levels (mean 20,270 mU/mL, range 12,090 to 43,164 mU/mL) that significantly decreased within 48 hours of physiologic amputation (mean 6,488 mU/mL, range 2,250 to 13,580 mU/mL). Mechanical ventilation and cardiovascular support were required in four patients. All patients had transient episodes of renal insufficiency with two progressing to anuric renal failure and requiring dialysis. One patient's renal failure resolved after 56 days, but the other patient died of a cerebrovascular accident 22 days after initiation of physiologic amputation. The mean duration of physiologic amputation was 15.6 days (range 5 to 32 days) with no significant complication due to physiologic amputation. All five patients had surgical amputation successfully. Three patients survived. The two deaths in the study were due to a cerebrovascular accident in one patient and a cardiopulmonary arrest in another. Physiologic amputation is a treatment option that halts myonecrosis, prevents myoglobinuria, and lessens the risk of associated acute renal failure. Physiologic amputation may be appropriately used in patients with myoglobinuria due to extremity myonecrosis who are deemed too critically ill to survive emergency amputation. PMID- 8211326 TI - Procedural complications of electroconvulsive therapy: assessment and recommendations. AB - We surveyed procedural techniques in 804 routine clinical sessions of electroconvulsive therapy (ECT) over 4 2/3 years. No significant problems occurred. Side effects as agitation, physical complications such as urinary stasis, and protocol deviations such as failure to use the bite block were occasionally documented. Mechanical difficulties such as trouble gaining intravenous access and medicinal problems such as inappropriate dosing were rare. Our assessment resulted in a more precise method of diminishing the risks of ECT. For example, the chin is held manually, closing the mouth during delivery of the stimulus, to obviate oral trauma. Similarly, electrode contact is always verified visually and with the ECT machine "self-test" just before each treatment. Both cuff and electroencephalographic means are used to determine seizure timing. ECT is safe; a carefully applied protocol should make it safer. PMID- 8211325 TI - Epidural narcotic analgesia after thoracotomy. AB - The benefits of epidural narcotic analgesia (ENA) have been documented in mixed surgical populations. To assess the safety and utility of ENA after thoracic surgery and to assess potential interactions with intraoperative intravenous narcotics (IIN), we retrospectively examined the records of 130 consecutive patients having thoracotomy. The 116 patients who received ENA required a mean of 0.19 mg/kg of intravenous morphine sulfate (MS) within the first 48 postoperative hours, as opposed to 0.44 mg/kg for patients who did not receive ENA. The place in which nonepidural patients were extubated most frequently was the operating room (71%), followed by the intensive care unit (21%) and the recovery room (7%). Percentages were similar for epidural patients: 71% were extubated in the operating room, 20% in the intensive care unit, and 9% in the recovery room. Nonepidural patients had an immediate mean postoperative PCO2 of 39.2 mm Hg, epidural patients a mean of 40.1 mm Hg. There were no technical complications due to epidural catheter placement, and no reintubation was required within the first 72 postoperative hours. The concomitant administration of IIN did not produce a significant difference in postextubation PCO2 in either group of patients, although increasing doses resulted in a lower percentage of patients extubated in the operating room or recovery room. We conclude that ENA may be safely administered to patients having thoracotomy, and it diminishes the need for postoperative intravenous narcotics. PMID- 8211327 TI - Bats, cats, and rabies in an urban community. AB - Bats are the primary vectors of rabies in humans in the United States. In the urban environment they generally are found within buildings where they may bite people or be attacked by cats or dogs. Given the high probability that any bat that bites a person may be rabid, antirabies prophylaxis should be administered as soon as possible after the incident. This should not be delayed pending laboratory results on the bat. Children should be taught to avoid contact with moribund bats. Cats are more likely to be involved with rabid bats than dogs, but they are less likely to be vaccinated against rabies. The occasional rabid cat in an urban community may have acquired its infection from a bat. Therefore, it is vital that communities enforce rabies vaccination for cats as well as dogs. PMID- 8211328 TI - Evaluation of alimentary tract foreign body: clinical and imaging review of 100 consecutive cases. AB - We investigated the cases of 100 consecutive patients with alimentary tract foreign bodies for clinical findings and use of imaging and compared our findings with those of other reported series. Most of our patients were children, and the alimentary tract foreign body was metal in most cases. There was no undue morbidity or mortality related to either conservative or interventional treatment. Imaging was useful in diagnosis and management of cases. Use of computed tomography and magnetic resonance imaging in evaluation of alimentary tract foreign bodies is discussed. PMID- 8211329 TI - Protocol Doppler color flow imaging immediately after kidney transplantation. AB - Doppler color flow imaging has been used to identify obstruction, rejection, and nonfunctioning renal allografts. When done in the immediate posttransplant period on poorly functioning kidneys, it allows early and accurate detection of surgically correctable changes such as arterial or venous thrombosis or early obstruction by blood, urine, or lymph. Further, it determines changes in intrarenal flow patterns that may indicate early transplant dysfunction, such as acute tubular necrosis and/or acute rejection as well as obstruction. Additionally, baseline values can be obtained in uncomplicated cases for serial follow-up. Between July 1980 and February 1991, 20 transplant patients had Doppler color flow imaging in the immediate posttransplant period. The kidney contour, perirenal collections, vessel flow patterns, and resistive indexes were assessed. In two patients, immediate surgical intervention salvaged the allograft. In several other patients with primary nonfunctioning kidneys, the study distinguished between acute tubular necrosis and obstruction due to external compression. We concluded that protocol Doppler color flow imaging is valuable in the immediate posttransplant period for determining surgically correctable complications. PMID- 8211330 TI - Macrosomatia and ultrasonography: what is the problem? AB - It has been claimed that sonographic techniques offer no advantages over palpation of the maternal abdomen for detection of macrosomatia. We studied a group of 498 pregnant patients, 36 (7.2%) of whom gave birth to infants having macrosomatia. A sensitivity of 67%, specificity of 97%, and positive predictive value of 67% was obtained using our method without significant systematic error. Three problems that could reduce the value of ultrasonography in the detection of macrosomatia were detected: (1) use of equations with systematic errors; (2) human bias; and (3) use of ultrasonography machines/transducers with insufficient capacity. PMID- 8211331 TI - Hepatic tumors: role of computed tomographic arterial portography in surgical planning. AB - Various imaging modalities currently used to evaluate liver tumors include magnetic resonance imaging, ultrasonography, contrast-enhanced computed tomography, and computed tomographic arterial portography. In our review of 28 cases, we found CT arterial portography to be very sensitive, and in 5 of these 28 cases CT arterial portography was a key factor in altering the course of therapy. PMID- 8211332 TI - Etiology of venous ulceration. AB - The etiology of venous ulceration is far more complex than Homans' theory of stagnation and hypo-oxygenation. Indeed, studies have shown that flow in lipodermatosclerotic limbs is actually faster than normal. We suggest, therefore, that the terms "stasis dermatitis" and "stasis ulcer" be dropped from medical parlance. The term "lipodermatosclerosis with ulceration" as used by the British, or simply "venous ulcer," would seem more appropriate. Venous hypertension, produced by incompetence of deep and communicating vein valves and thrombosis of segments of the deep system, is closely correlated with the development of venous ulcers. Precisely how this venous hypertension translates into ulceration is unclear. Burnand et al showed that fibrin cuffs are deposited around the capillaries in lipodermatosclerotic limbs. These cuffs may serve as barriers to the diffusion of oxygen, leading to local ischemia and epidermal necrosis. Others suggest that trapped leukocytes in the microcirculation alter capillary permeability by releasing various inflammatory mediators that hasten the flow of fibrinogen across the capillary membrane and promote the formation of fibrin cuffs. Proof of this hypothesis is still lacking, but may eventually come from using radioactive WBC tagging procedures. A synthesis of these two theories may in fact explain the etiology of venous ulceration. PMID- 8211334 TI - Abuse of over-the-counter dextromethorphan by teenagers. AB - Dextromethorphan, the d-isomer of the opiate agonist levorphanol, has none of the analgesic or sedative effects associated with the opiates and is approved for over-the-counter use as an antitussive. It is available, in various combinations with other medications, in nonprescription cough suppressant and common cold formulations, and its availability in the United States is not controlled. In this paper we have reported two cases of recreational use of dextromethorphan containing cough syrup by two unrelated teenage boys. Despite the safety of this medication when used at the recommended dosage, there have been cases of "recreational" use of dextromethorphan as well as death by overdose. Although usually thought to be nonaddictive, dextromethorphan produces a substance dependence syndrome, and physicians should be aware of its abuse potential, particularly by youths. PMID- 8211333 TI - Pediatric cervicofacial actinomycosis. AB - It is well recognized that cervicofacial actinomycosis is rare in children. We have summarized the cases in the English language literature and reported a recent case from our hospital. In only 10% of clinical situations is actinomycosis the primary diagnosis. Failure to consider actinomycosis in the differential diagnosis of a cervical mass may compromise the ability to make the diagnosis, given the fastidious nature of the most common pathogen, Actinomyces israelii. Indeed, the recovery rate of only 30% in some of the earlier studies of actinomycosis may have been in part due to this oversight. The correct diagnosis, however, is imperative because the treatment of actinomycosis is different from that of routine cervical adenitis in that actinomycosis requires high doses of penicillin over a prolonged time, since it is subject to relapse. Our case serves as a reminder to consider actinomycosis as the possible cause of a cervical mass, not only in adults, but in children as well. PMID- 8211335 TI - Maternal death from severe retroperitoneal fibrosis. AB - Idiopathic retroperitoneal fibrosis is uncommon in pregnancy. We have described the case of a pregnant patient with a benign retroperitoneal spindle cell tumor involving the distal duodenum, right ureter, and right iliac artery and vein. She was treated with a left ureteral stent and a right percutaneous nephrostomy. Ultimate cause of death was electrolyte imbalance due to bowel obstruction. PMID- 8211336 TI - Acquired methemoglobinemia from multiple oxidants. AB - Phenazopyridine has been associated with methemoglobinemia in patients who have received an overdose, have decreased renal function, or are discovered to be unusually susceptible to the drug (ie, they may have an undetected NADH methemoglobin reductase deficiency). The case we have presented is unusual in that normal doses of phenazopyridine were given, no renal dysfunction was evident, and our patient had previously been given this drug without complication. Methemoglobinemia appeared to be the result of metabolic overload by multiple oxidants (phenazopyridine and lidocaine) of the normal reductase pathways in the erythrocytes. We saw no evidence to indicate that bupivacaine contributed to its development. Enzyme pathway changes induced by chemotherapy should be considered, though few studies have linked alterations of enzyme levels and pathways with chemotherapy and malignancy. PMID- 8211337 TI - Mediastinal mass with right pleural effusion. AB - We have described the case of a 65-year-old man who had a right hemothorax from rupture of an aneurysm of the ascending thoracic aorta and survived. This type of subacute presentation with survival of the patient has not been documented previously in contemporary medical literature. PMID- 8211338 TI - Endobronchial hamartoma treated by bronchoscopic excision. AB - Endobronchial hamartoma is a rare lesion, with only 65 cases previously reported in the English literature. An additional case is reported here. The patient was successfully treated by bronchoscopic excision of the hamartoma. PMID- 8211339 TI - Septic shock in an elderly patient: unusual presentation of echovirus infection. AB - We have described a case of fulminant echovirus infection that progressed rapidly to purpura and septic shock. To our knowledge, this is a previously unreported presentation of acute echovirus infection in an immunocompetent adult. PMID- 8211340 TI - Sedimentation level in intracerebral hematoma in patients receiving anticoagulation therapy. AB - We have described two cases of spontaneous intracerebral hematoma, characterized by sedimentation level seen on unenhanced cerebral CT, in patients receiving anticoagulation therapy. Anticoagulation or coagulopathy may be important in producing sedimentation levels. The "sedimentation level" is a more accurate term than the commonly used "blood-fluid level" or "hematocrit effect." PMID- 8211341 TI - Platelet dysfunction associated with clozapine therapy. AB - Clozapine, an atypical antipsychotic agent used in cases of treatment-resistant schizophrenia, is known for its relative absence of extrapyramidal side effects and its potential hazardous effect on white blood cell function. We have described a case of clozapine-associated epistaxis and reduction of the platelet count. Discontinuance of clozapine therapy resulted in cessation of epistaxis followed by normalization of the platelet count. We suggest routine monitoring of platelet count and function in patients treated with clozapine. PMID- 8211342 TI - Endometriosis and ascites. AB - A 29-year-old black woman had increasing abdominal girth, dullness to percussion, and an irregular mass in the left adnexal region. At laparotomy, 6 L of dark brown fluid was removed, and the abdominal cavity had the appearance of extensive carcinomatosis. Subsequent histology was consistent with endometriosis. Fourteen cases of endometriosis producing symptoms resembling ovarian cancer have been previously reported. Of the 10 patients whose race was mentioned, 9 were black, as was our patient. The etiology of the ascites is unknown. Histologically, the endometrial implants show dense stroma and a slightly hyperplastic epithelium rather than the physiologic proliferative endometrium usually associated with endometriosis. This leads us to question the prognosis of the lesion despite its apparently benign histology. PMID- 8211343 TI - Staphylococcus aureus meningitis associated with pyogenic infection of the sacroiliac joint. AB - Although we have reported the first case of Staphylococcus aureus meningitis due to pyogenic arthritis of the sacroiliac joint, this finding is actually not surprising, given the strong association between this form of meningitis and underlying bone, joint, and soft tissue infections. The physician faced with a case of meningitis due to S aureus in a patient without a history of trauma or neurosurgical manipulation must do a prompt and thorough search for underlying infectious conditions. In the case of sacroiliitis in particular, a high index of suspicion needs to be maintained, given the difficulties and delays in diagnosis associated with this infection. Radionuclide scanning with 99mTc or 67Ga is usually helpful in the early confirmation of this condition, the presence of which may be suspected on the basis of thorough physical examination. PMID- 8211344 TI - Mitral valve disease associated with long-term ergotamine use. AB - A 43-year-old woman with symptoms and signs of congestive heart failure and intermittent claudication was found to have moderately severe mitral stenosis and regurgitation, as well as severe bilateral upper and lower extremity arterial occlusive disease. She had a history of migraine headaches and had abused ergotamine tartrate (Cafergot) chronically for more than 20 years. Only rare instances of valvular heart disease have been associated with chronic ergotamine toxicity, with the majority of previously reported cases based on auscultatory findings alone. PMID- 8211345 TI - Effect of serum lithium levels on thyrotropin levels. AB - Previous research has demonstrated laboratory-detected hypothyroidism as a consequence of lithium usage in 3% to 30% of all recipients and abnormal TSH secretion in up to 15%. This has generally been considered a non-dose-related consequence of lithium therapy. This study examined whether serum levels of lithium are related directly to changes in thyroid function. In a retrospective review, data from 39 cases were analyzed for correlations between serum lithium level, TSH, T3 RU, and T4 by RIA. A positive correlation was found between changes in serum lithium concentration and changes in TSH level. None of the other variables measured showed any correlation. Results of this study suggest that lithium-induced changes in TSH are serum level dependent. Possible mechanisms and clinical implications have been discussed. PMID- 8211346 TI - Recurrent meningitis. PMID- 8211347 TI - Presence of lupus anticoagulant in patients infected with the human immunodeficiency virus. PMID- 8211348 TI - Final exit: the slippery slope begins? PMID- 8211349 TI - Management of hypertension in older patients. AB - Reduction of hypertension, whether systolic and diastolic or isolated systolic, is associated with significant reductions in mortality and morbidity rates even in older asymptomatic patients, particularly those less than 80 years old. The increased availability of antihypertensive preparations makes it possible to individualize the choice of therapy to meet the particular needs of the older patient. Although most presently available antihypertensive agents are effective, each one possesses different properties and none is free of side effects. We review the indications for and the action and side effects of diuretics, angiotensin converting enzyme inhibitors, calcium channel blockers, and adrenergic blocking drugs, and we offer treatment suggestions for hypertension associated with other diseases such as diabetes mellitus, heart failure, peripheral vascular insufficiency, depression, dementia, and urinary incontinence. Orthostatic hypotension is particularly serious in older patients because it may precipitate falls. It is also possible that the relationship between blood pressure levels and mortality and morbidity risks is not linear but J-shaped, both low and high levels increasing risks. Caution in treating hypertensive elderly patients will minimize the incidence of side effects. PMID- 8211350 TI - Cholesterol and the older adult. AB - The National Cholesterol Education Program and physician/patient awareness of the risks of hypercholesterolemia have resulted in aggressive screening and treatment of elevated cholesterol levels. The "one size fits all" concept has been used as the criterion for intervention. However, this has been promulgated without convincing evidence that levels of cholesterol are as important in older individuals as in those of middle age. Clearly, cholesterol is not the only contributor to cardiovascular risk, and other risk factors such as smoking, hypertension, diabetes, and obesity should not be ignored. To prevent unnecessary intervention, overzealous interpretation of cholesterol values should be avoided. PMID- 8211351 TI - Ischemic heart disease in the elderly: the role of coronary angioplasty and coronary artery bypass grafting. AB - Management of ischemic heart disease in the elderly is complex. Invasive therapies such as percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) are associated with significant morbidity and mortality. The short-term advantage of PTCA is that its associated noncardiac morbidity and mortality are less than that of CABG, particularly in the incidence of stroke. Unfortunately, PTCA revascularization is less complete and less durable than CABG revascularization. The advantages of CABG are that cardiac revascularization is more complete, the result is more durable, and long-term results are improved over those of PTCA. Conversely, the initial morbidity and mortality are higher for CABG and are adversely affected by factors such as recent myocardial infarction, lung disease, and renal failure. We provide an overview of the results and outcomes of PTCA and CABG in the elderly, as well as suggestions for management. PMID- 8211352 TI - Surgical management of carotid artery atherosclerotic disease. AB - Cerebrovascular disease remains an important cause of disability and death in the geriatric population. This paper reviews the current state of knowledge with respect to the pathogenesis and medical and surgical treatment of carotid atherosclerosis. The majority of strokes are probably due to embolization from an ulcerated atherosclerotic plaque at the carotid bifurcation rather than from ischemia produced by global reduction in cerebral blood flow related to obstruction of the carotid arteries. Ultrasonography is an appropriate screening examination, but most vascular surgeons consider contrast angiography to be essential in the preoperative evaluation. Large clinical trials have evaluated the efficacy of stroke prevention by carotid endarterectomy in symptomatic patients. The North American Symptomatic Carotid Endarterectomy Trial clearly demonstrated a benefit of surgery in stroke prevention as compared with optimal medical therapy after only 18 months of follow-up. The European Carotid Surgery Trial and a VA Cooperative Study produced similar conclusions. Much less information is available concerning the patient with carotid atherosclerosis who has no cerebral symptoms. No convincing evidence that surgery is beneficial has yet been demonstrated, but a large multicenter clinical trial (Asymptomatic Carotid Atherosclerosis Study) remains in progress. PMID- 8211353 TI - Treatment of myocardial ischemia and myocardial infarction in the elderly. AB - The diagnosis of coronary artery disease in the elderly is problematic because older patients often present atypical symptoms or are asymptomatic. Once coronary disease is diagnosed, the proper course of treatment is not always clear, since few studies have focused on patients older than 65 years. Moreover, older patients often have medical conditions that may aggravate coexisting cardiovascular problems or interfere with conventional pharmacotherapy. For these reasons many physicians who treat cardiovascular problems aggressively in younger patients are reluctant to do so in older individuals. There is considerable evidence, however, that older patients could benefit as much or more from aggressive therapy because of their greater risk of mortality from myocardial ischemia and infarction. PMID- 8211354 TI - Pulmonary hypertension and cor pulmonale. AB - This article is directed primarily to primary care physicians. The challenge is to suspect, diagnose, and treat pulmonary arterial hypertension when treatment is most effective and before the effects of cor pulmonale become fully manifested. A good history and physical examination should be followed by electrocardiographic and roentgenographic evaluations. Of additional value are arterial blood gas measurements, two-dimensional echocardiography, first-pass radionuclide angiography, and catheterization of the right ventricle. Chronic obstructive pulmonary disease (COPD) is one of the more common etiologies of pulmonary hypertension and cor pulmonale. COPD is most common in the elderly and cor pulmonale is fairly common among those with COPD; therefore, hypoxic pulmonary hypertension and the resultant cor pulmonale occur mostly in older patients. Because early signs are nonspecific, diagnosis and treatment are often delayed until the pulmonary disorder is severe. Thus it is imperative that the primary care physician be cognizant of this serious problem. Standard treatment of left ventricular failure (ie, "congestive heart failure") could have adverse effects in patients with cor pulmonale. PMID- 8211355 TI - Use of psychometric measures and nonorganic signs testing in detecting nomogenic disorders in low back pain patients. AB - The effect of financial compensation on responses to psychometric testing was studied in 231 chronic back pain patients. Item by item comparison of responses to two tests, readministered within 4 hours, yielded inconsistency scores. These inconsistency scores, along with scores on other psychometric measures and on Waddell's nonorganic signs test, of a group of 97 patients anticipating or receiving financial compensation (AFC), and a group of 134 patients not receiving or anticipating financial compensation (non-AFC) were compared. The AFC group had significantly higher mean scores than did the non-AFC group on the inconsistency measures, on almost all psychometric tests and on nonorganic signs. Almost all non-AFC subjects scored "0" on nonorganics, whereas 83% of AFC subjects scored "2" or higher. Prediction analysis revealed that the nonorganics score alone can predict AFC/non-AFC status; 90% of subjects were correctly classified. The inconsistency scores correctly classified 78%. Together, they correctly classified 93%. It was concluded that nonorganic scores and inconsistency scores (as defined by the investigators) distinguish between, and can predict membership in AFC and non-AFC groups. The significantly higher inconsistency scores obtained by the AFC group suggest that these psychometric test results are unreliable and hence invalid for this group. PMID- 8211356 TI - Surgical treatment for the far lateral herniated lumbar disc. AB - Twenty-nine patients underwent surgery for far lateral herniated nucleus pulposus. Average patient age was 65 years in the 14 male and 15 female patients involved. The L4-5 disc was the most commonly herniated level (59%) followed by L3-4 (31%), L5-S1 (7%), and L2-3 (3%). All patients were initially seen with radiculopathy and 23 patients (79%) had motor weakness. A pars interarticularis sparing technique is described for approaching this type of disc herniation. This approach allows direct visualization of the disc and involved root. The results are encouraging with 72% of patients having good or excellent relief of pain. Seventy-one percent of those with preoperative weakness had no weakness or improvement in strength postoperatively. In general, far lateral herniated nucleus pulposus occurs in older patients and at high lumbar disc levels. Postoperative results are similar to the more common posterolateral herniated nucleus pulposus in patients of the same age group. A surgical approach is described to better address the less familiar anatomy. PMID- 8211357 TI - Attempted experimental modification of the postlaminectomy membrane by local instillation of recombinant tissue-plasminogen activator gel. AB - A prospective, randomized, blinded trial involving 25 adult mongrel dogs was performed to evaluate whether placement of a fat graft or local instillation of recombinant tissue-plasminogen activator gel (rt-PA) could modify the development of a postlaminectomy membrane. One component of the study involved the performance of a lumbar laminectomy and placement of gel rt-PA, free fat, or no tissue placement over the exposed dura mater. Three months later the animals were killed and sections of spine were removed en bloc, decalcified, and examined histologically. No significant differences were found in the degree of cellular fibrosis or heavy collagen production. A similar laminectomy at another lumbar level was also followed by gel rt-PA, free fat, or no tissue placement. Three months after surgery, surgery was performed again at this level immediately before death. There were no differences in the adhesiveness of the laminectomy membrane to dura mater or roots. It was concluded that the local instillation of gel rt-PA after laminectomy did not inhibit scar formation or scar adherence to the dura mater. PMID- 8211359 TI - Metastatic lesions of the cervical spine. A retrospective analysis of 20 cases. AB - Twenty patients were surgically treated for metastatic lesions of the cervical spine. The primary cancer was known in 14 patients, breast cancer being the most prevalent. In six patients, the cervical metastasis was revelatory of cancer. Fourteen patients showed neurologic deficit. For the upper cervical spine, a posterior approach was employed. From C3 to C7, an anterior surgical approach was preferred. Since 1986, the authors have performed, after a corpectomy of one or more vertebrae, an acrylic corpoplasty reinforced with an anterior plate. Two cases of neurologic deterioration and one instability in lesions involving the lower cervical spine were encountered. The survival period for 17 patients was, on average, 11 months (ranging from 8 days to 46 months). Nineteen patients had pain relief. Of 14 patients with neurologic deficit, 9 experienced partial or total improvement. Three patients showed no neural recovery, whereas surgery worsened the conditions of two patients. For lower cervical lesions, the anterior approach is recommended even for C3 (retropharyngeal approach) or for cervicothoracic lesions. PMID- 8211358 TI - Anterior cervical plate fixation with the titanium hollow screw plate system. AB - Although anterior cervical plates provide excellent fixation for the anterior column, the potential risk for injury to the spinal cord or soft tissues involved with their use has been the reason they have not gained universal acceptance. Morscher introduced a system that attempts to prevent the migration and loosening of screws by using a cross-split screw head that can be locked into the plate. The secondary advantage of this system is that it eliminates the requirement for posterior cortex purchase and thereby decreases the risk for spinal cord injury. This article reports the authors' experience using the Morscher titanium hollow screw cervical plate system. Forty-two patients in the series underwent anterior cervical arthrodesis for degenerative disease or trauma. The average number of levels fused were two. The fusion rate was 100%. Significant hardware loosening occurred in two patients. There was no iatrogenic injury to the spinal cord or esophagus. In conclusion, the titanium hollow screw cervical plate provides immediate stable fixation with minimal complications. Its use should be considered in the surgical treatment of patients requiring multilevel anterior cervical arthrodesis. PMID- 8211360 TI - Concomitant noncontiguous thoracolumbar and sacral fractures. AB - Seventeen patients were identified with concomitant thoracolumbar and sacral fractures representing 26% of sacral fractures and 7.7% of pelvic fractures. The thirteen men and four women exhibited a bimodal age distribution. There were thirteen vertical compression thoracolumbar fractures, three transverse process fractures, and one traumatic herniated nucleus pulposus. There were seven Zone I, seven Zone II, and three Zone III sacral fractures using the Denis classification. Five of the sacral fractures were missed on initial presentation. Four of the patients had neurogenic bowel or bladder symptoms. Seven of the thoracolumbar fractures and three of the sacral fractures were treated operatively. Results were generally good or excellent unless significant neurologic injury was present at initial presentation. The authors recommend aggressive computed tomographic evaluation of the sacrum in any suspicious pelvic trauma or when the neurologic lesion does not match the more proximal bony lesion. They hypothesize that decompression of both sacral and thoracolumbar lesions may be necessary if either lesion could be responsible for neurogenic bowel or bladder symptoms. PMID- 8211361 TI - Paraspinal soft-tissue sarcoma. Classification of 14 cases. AB - Fourteen patients were treated surgically for soft-tissue sarcoma arising in the paraspinal muscles. Eleven patients received adjuvant irradiation administered before or after resection. In describing the treatment and outcomes of these patients, a new classification of paraspinal soft-tissue sarcoma is introduced that is based on the anatomic relationship of the tumor to the spinal lamina and the epidural space. This classification can be used in planning combined modality treatment for paravertebral sarcomas. Lesions that extend through the lamina into the epidural space present an unanswered problem for local control. PMID- 8211362 TI - Articular facets of the human spine. Quantitative three-dimensional anatomy. AB - This study provides the quantitative three-dimensional surface anatomy of the articular facets for the entire human vertebral column based on a study of 276 vertebrae. Means and standard errors of the means for linear, angular, and area dimensions of the superior and inferior articular facets were measured for all vertebrae from C2 to L5. Facet orientations were described as angles with respect to the sagittal and transverse planes and also as card angles. The plane angles are similar to the angles seen on traditional radiographic views--radiographs and computed tomographic scans. The card angles, a new concept, are better at helping visualize the three-dimensional orientations of the facets. Excluding the superior C2 facet, the following minimum and maximum dimensions were found for the facets from C3 to L5: width = 9.6-16.3 mm; height = 10.2-18.4; surface area = 72.3-211.9 mm2; interfacet width = 20.8-40.6; interfacet height = 12.2-33.0 mm; transverse plane angle = 41.0-86.0; sagittal plane angle = 67.4-154.8; X-card angle = 41.0-86.0; and Y-card angle = 5.8-66.1. The quantitative anatomy of the facets may improve the understanding of the spinal anatomy, help improve the clinical diagnosis and treatment, and provide the necessary data for constructing more realistic mathematical models of the spine. PMID- 8211363 TI - A study of the angle of inclination and facet curvature of superior lumbar zygapophyseal facets. AB - The angle of inclination and depth of curvature of L1-L5 of the superior articular facets of both sexes were measured in 112 lumbar spines. In addition to standard statistical methods data were also analyzed to show various degrees of departure from the "normal." The L3 vertebra showed the least variation and L5 and L1 showed the most. The angle and depth of L1 to L5 showed a small, albeit statistically significant, difference between the two sexes but no laterality differences were apparent. At L1 12.5% of males and 10.4% of females revealed an asymmetry of angle exceeding 20, and at L5 3.1% of males and 1.7% of females showed such tendency. An asymmetry of the depth of curvature of the articular facets exceeding 1.5 mm was recorded in 12.5% of males and 8.3% of females at L1 and 6.5% of males and 2.1% females at L5. The expected values of depth of curvature were lowest at L1 and highest at L3 and L4. It is suggested that a more quantitative approach to the study of the zygapophyseal joint would enhance precision and facilitate meaningful interlaboratory comparisons of published data. PMID- 8211364 TI - The iliac buttress. A computed tomographic study of sacral anatomy. AB - Fifty randomly selected computed tomographic (CT) scans of the lumbosacral spine (25 males and 25 females) were studied to determine: 1) if the lateral sacral masses could safely accept a 7 mm diameter rod (i.e., intrasacral rod insertion) and 2) what percentage of patients, both males and females, demonstrated coverage of the posterolateral sacrum by the ilia (i.e., iliac buttressing). In all patients the lateral masses (i.e., the lateral intrasacral mass measurements) appeared wide enough on CT to allow for safe insertion of a 7 mm diameter rod, or other similar size implant, down to at least the level of S2. The smallest distance measured for the width between the posteromedial margin of the sacroiliac joint and the lateral cortex of the S1 neuroforamen (i.e., the lateral intrasacral mass measurement) at its location approximately midway (anteroposterior) through the sacrum on CT cuts was 17 mm (mean 28 mm). This would appear to give adequate room for a 7 mm diameter rod to be inserted at this level in the lateral sacrum (i.e., intrasacral rod insertion). Forty-six patients (24 males, 96%; and 22 females, 88%) appeared to have sufficient CT coverage of the sacrum to conceptually provide for so called "sacroiliac buttressing" of rods, if rods or other implants were to be inserted distally into the lateral masses. After a review of the sacral anatomy by CT it appears that: 1) insertion of rods into the lateral sacral masses (i.e. intrasacral rod insertions), or intrasacral fixation with other similar size implants, would be possible and apparently safe; and 2) the ilia along with the sacroiliac interosseous ligaments sufficiently surround the back and sides of the posterolateral sacrum in most patients (92%), at least by CT assessment, to conceptually offer an indirect "buttress" for implants so inserted. Theoretically, this could biomechanically help resist the flexural loads across the lumbosacral level and possibly provide a method for improved sacral fixation with spinal instrumentation in certain patients. PMID- 8211365 TI - Anomalies associated with vertebral malformations. AB - A review of 218 patients with congenital vertebral anomalies demonstrates that 61% of patients had associated abnormalities affecting seven systems. The type of vertebral anomaly did not predict the location or type of associated abnormality. The site of vertebral anomaly did correlate with the occurrence of some associated diagnoses. The most common abnormalities associated with vertebral malformation were cranial nerve palsy, radial hypoplasia, club feet, dislocated hip, Sprengel's deformity, imperforate anus, hemifacial microsomia, and renal and cardiac anomalies. Comprehensive evaluation of patients with vertebral anomalies will be enhanced by knowledge of the type and frequency of associated anomalies. PMID- 8211366 TI - Outcome assessment after epidural corticosteroid injection for low back pain and sciatica. AB - Epidural corticosteroid injection is a relatively effective treatment for low back pain and sciatica with a low incidence of side effects, although the patient's perspective in terms of outcome and satisfaction has not been studied well. The assessment of outcome in low back pain patients is complex. Three types of measure were compared: 1) a clinical score, 2) patient ratings of pain and disability, and 3) patient satisfaction ratings. There were significant discrepancies among the results. Consequently, clinical trials using different outcome measures may reach different conclusions. It therefore is vital to have planned the study carefully in advance, considering the questions to be asked, especially in this area, where patient-derived measures (e.g., "patient satisfaction") are so important. This study of 35 patients showed a fall in clinical signs/symptoms, disability, and pain 1 week after the injection, with maintenance of the reduction in disability at 3 months. Eighty-five percent reported at least some improvement at 1 week and 43% had improvement lasting 3 months. Patients with a more depressed mood had higher levels of disability both before and after the procedure. Anxiety before the procedure did not adversely affect outcome, and it was well tolerated by most patients. At 3 months 83% were satisfied with the treatment they had received and a patient satisfaction questionnaire gave similar results. We continue to recommend this treatment as a well-tolerated procedure, with which most patients are satisfied. PMID- 8211367 TI - Low back pain in military basic trainees. A pilot study. AB - Many studies have been done to elucidate risk factors for low back pain in the general population. A review of the literature reveals that no studies have described low back pain in the military. A pilot study was performed to evaluate the incidence, prevalence, and risk factors of low back pain in a group of military basic trainees. We found an incidence of 17%. Of numerous demographic and risk factors studied, only cigarette use was significantly associated with low back pain. A previous history of chronic low back pain was not significantly associated with low back pain during training but was predictive of difficulty completing training. The authors conclude that low back pain occurs frequently during Army basic training and that cigarette smoking is associated with increased risk. PMID- 8211368 TI - Electrophysiologic evaluation of intermittent sacral nerve dysfunction in lumbar spinal canal stenosis. AB - Intermittent sacral nerve dysfunction, induced by walking in lumbar spinal canal stenosis, may cause symptoms including hyperesthesia and pain in perineum, urinary bladder incontinence, and penile erection. However, it is difficult to objectively document these symptoms. Evoked external urethral sphincter potentials by conus medullaris stimulation were measured both before walking and after walking in five patients who complained of sexual organ or urinary dysfunction during walking, and were compared with simultaneously induced sacral nerve symptoms. These potentials were also measured during surgery. Sacral nerve symptoms were reproduced by walking 80-350 meters (average 177.5 m). These potentials disappeared in one patient and were decreased in four patients at the time when the claudicant symptoms disabled the patient during walking. The amplitude subsequently recovered in keeping with relief of those symptoms during rest. Monitoring of these potentials during surgery showed an increase of amplitude shortly after the decompression procedure of the cauda equina. In conclusion, this measuring method was valuable as an objective evaluation of intermittent sacral nerve dysfunction in lumbar spinal canal stenosis. PMID- 8211369 TI - Comparison of sacrospinalis myoelectric activity and pain levels in patients undergoing static and intermittent lumbar traction. AB - The purposes of this study of low back pain patients were to determine: 1) if presence of sacrospinalis myoelectric activity is a consistent phenomenon in supine and prone positions; 2) if there is a difference between magnitudes of myoelectric activity for two types of lumbar traction (static and intermittent); and 3) if there is a difference in patient perceived pain level after traction between the two types of traction. Results show that surface electrode myoelectric activity is absent in resting supine and prone positions, there is no significant difference in magnitude of myoelectric activity between the two different types of traction, and more than 50% of patients in both traction groups experienced decreased pain after traction. PMID- 8211370 TI - New vertebral body impactors for posterolateral decompression of burst fracture. AB - A new type of impactor was developed to decompress the anterior aspect of the vertebral body. These instruments are particularly useful for cases of burst fracture. PMID- 8211371 TI - Cervical spondylolysis. Report of two cases. AB - Two cases of cervical spondylolysis are presented. Both cases were discovered during radiographic examination after incidental trauma. The first patient experienced transient quadriplegia that spontaneously resolved and the other experienced only neck pain. Further radiographic evaluation of the first patient revealed significant spinal cord compromise, ultimately requiring decompression and fusion. The second patient's cervical spine proved stable to dynamic studies and was without cord compromise. PMID- 8211372 TI - Thoracic spinal stenosis associated with renal osteodystrophy. Diagnosis based on magnetic resonance imaging and computed tomography. AB - We describe a case of thoracic myelopathy in a patient with renal osteodystrophy. The patient had chronic renal failure for longer than 20 years and had skeletal changes indicative of renal osteodystrophy, before the onset of myelopathy. Association between spinal stenosis and this entity has been documented only once before in the lumbar region. This is therefore the first case of thoracic myelopathy due to severe stenosis in just one vertebra in a patient with renal osteodystrophy, which was documented by computed tomography as well as magnetic resonance imaging and proven by histopathology. PMID- 8211373 TI - A new management approach to decompression, posterior stabilization, and fusion for cervical laminar exostosis with cord compression in a case of diaphyseal aclasis. Case report and review of the literature. AB - A rare case of cervical cord compression secondary to laminar exostosis (in an adolescent girl with diaphyseal aclasis) is described, which was treated by decompression, posterior stabilization by a Hartshill rectangle, and posterolateral facet fusion. A brief summary of the clinical presentation is given as well as the surgical technique employed and a brief review of the relevant literature. Posterior stabilization and posterolateral fusion are emphasized, with a view to minimize the inevitable "postlaminectomy kyphosis." This is the first report of such an aggressive treatment protocol even described for a similar lesion. PMID- 8211374 TI - Spinal cord compression secondary to osteoblastic metastasis. PMID- 8211375 TI - Analysis of mutations introduced into the chromosomal immunoglobulin mu gene. AB - We have introduced a pSV2neo-derived vector that contains a 2-base-pair (bp) deletion in its immunoglobulin mu gene constant region into hybridoma cells bearing a single copy of the wild-type chromosomal immunoglobulin mu gene. Homologous recombination between the transferred mutant C mu region and the wild type chromosomal C mu region is expected to introduce the 2-bp deletion into the chromosomal mu gene, generating recombinant cells synthesizing noncytolytic IgM. Analysis of the DNA in independent noncytolytic transformants indicates that in one case the mu gene has the structure expected for correct homologous recombination. Unexpectedly, the remaining transformants, bear chromosomal mu gene deletions. PMID- 8211376 TI - Isolation of new nonsense and frameshift mutants in the immunoglobulin mu heavy chain gene of hybridoma cells. AB - In order to expand the experimental material available for genetic and biochemical analyses of the natural immunoglobulin genes, we have isolated a variety of mutant mouse hybridoma cell lines. Some of these mutants have partial or complete deletions of the mu gene. Other mutants have nonsense or frameshift mutations in the exons encoding the variable and the second and third constant region domains of the mu heavy chain. When combined with earlier mutant data, this collection of genotypically and phenotypically tight mutants of known sequence spans most of the 10 kb of the mu gene, providing material for a variety of studies of genetic recombination and mRNA metabolism. PMID- 8211377 TI - Selection of a lysine-resistant CHO-K1 mutant with reduced amino acid transport through multiple systems. AB - High levels of L-lysine were used to select for resistant variants of Chinese hamster ovary (CHO-K1) cells. Surviving colonies were screened for altered lysine transport and two with reduced uptake were picked. Clone CH-Kr, derived from the more severely affected colony, was analyzed in detail. In starved cells the Vmax of lysine uptake in CH-Kr was half that of CHO while Km was unaltered. The intracellular pool of lysine, a substrate of cationic amino acid transport system y+, was significantly lower in CH-Kr. However, transport and pools of other amino acids, which are not substrates of y+, were also reduced in CH-Kr, as was the internal sodium concentration, while hexose import was increased. It appears that the mutation in CH-Kr is pleiotropic, affecting some general aspects of amino acid transport. PMID- 8211378 TI - Multiple regulatory elements ensure accurate transcription of a human ribosomal protein gene. AB - Previously we have shown that expression of a cloned human ribosomal protein gene, RPS14, depends upon regulatory sites located within the gene's proximal upstream DNA plus its first intron. In order to identify cis-active sequence motifs within the RPS14 promoter-enhancer complex, we transiently expressed a set of informative deletion clones in cultured Chinese hamster ovary cells. These experiments revealed three DNA sequence motifs that surround the S14 mRNA initiation site and are necessary for accurate transcription. Electrophoretic mobility shift, DNase I footprint, and methylation interference assays resolved two nuclear proteins, NF alpha-1 and NF beta-1, which bind specifically to these regulatory motifs. NF-alpha 1 recognizes a pair of 6-bp target motifs (5'-TTCCGG 3') that flank the 5' end of RPS14 exon I; and NF-beta 1 binds to a 10-bp target sequence (5'-CCGTGGGAAC-3') within the gene's first intron. Site-directed deletion mutations within the NF-alpha 1 and -beta 1 binding sites markedly inhibit S14 mRNA transcription. PMID- 8211379 TI - Sensitivity of Roberts syndrome cells to gamma radiation, mitomycin C, and protein synthesis inhibitors. AB - Roberts syndrome (RS) is a rare autosomal recessive disorder characterized by pre and postnatal growth retardation, limb reduction abnormalities, and craniofacial anomalies. Mitotic chromosomes from RS individuals display repulsion of heterochromatin regions or centromere splitting, leading to a railroad-track appearance of mitotic chromosomes. Abnormalities in metaphase duration, anaphase progression, nuclear morphology, and increased frequency of micronucleation have been reported in RS cells. Cells from RS heterozygotes are normal in these respects, and in vitro complementation of the defects in somatic cell hybrids has been reported. Therefore, in preparation for the isolation of cDNAs that complement the RS defect, we investigated various drug treatments to identify an agent that specifically involves the growth of RS cells. Based on the cytogenetic and cell biologic findings, we chose agents that increase micronucleation or inhibit protein synthesis. We found that RS cells are hypersensitive to gamma radiation, mitomycin C, G418 and hygromycin B, but not to colcemid or streptonigrin when compared to normal cells. DNA content and cell viability analysis confirmed that the sensitivity to gamma irradiation was primarily due to increased cell death. PMID- 8211380 TI - DNA methylation of the fragile X locus in somatic and germ cells during fetal development: relevance to the fragile X syndrome and X inactivation. AB - To obtain insights into mechanisms responsible for methylation of CpG islands on the inactive X chromosome of normal females, we examined methylation of the fragile X (FraX) locus in a variety of tissues from normal fetuses and adults, and from males with the FraX syndrome. We identified 20 CCGG sites (MspI-HpaII sites M1-M20) within a 12-kb BglII fragment that includes the CpG island. Sites M3-M18, within the 1.2-kb CpG island are unmethylated on the active X in normal males and females at all ages and in all tissues studied. In contrast, these sites are at least partially methylated on the inactive X chromosome in a variety of tissues from normal females by six weeks from conception. The exceptional tissues are chorionic villi and gonads, which are significantly undermethylated. In addition, fetal germ cells are unmethylated at site M3, which is methylated on the inactive X in other tissues; thus, the methylation imprint of the inactive X has been erased. Methylation of the locus on the fragile X chromosome is similar to that of the normal inactive X but is more extensive and less heterogeneous. This suggests that the expansion of the island and the greater number of CpGs that result from amplification of the CGG repeat enhance the methylatibility of the island. Additional studies show that the chromatin of the CpG island is nuclease hypersensitive on the active X but insensitive on both inactive and FraX. PMID- 8211381 TI - Regional mapping of the gene encoding dihydroorotate dehydrogenase, an enzyme involved in UMP synthesis, electron transport, and superoxide generation, to human chromosome region 16q22. AB - De novo UMP synthesis is a critical metabolic pathway for nucleic acid synthesis and for a variety of metabolic pathways. The pathway is a target for many widely used cancer chemotherapy agents, several of which are pyrimidine analogs. Humans and cattle have been described with mutations in UMP synthesis that lead to serious inborn errors of metabolism. Dihydroorotate dehydrogenase (EC 1.3.3.1) (DHODH) carries out the fourth committed step in the pathway and may also be important for mitochondrial electron transport and oxygen radical metabolism. We report here that the gene encoding this enzyme in humans is located in the chromosomal region 16q22. With the mapping of DHODH, the mapping of all the steps of UMP synthesis is complete. All three genes involved map to different human chromosomes. This information is important in consideration of regulation of UMP synthesis in mammals, including humans. PMID- 8211382 TI - [Fundamentals and applications of color-coded duplex sonography]. PMID- 8211383 TI - [Color-coded Doppler sonography of the leg veins. Fundamentals--indications- results--limitations]. PMID- 8211384 TI - [Secondary amyloidosis of the kidneys in Crohn disease: radiologic findings]. PMID- 8211385 TI - [Liver necrosis in a case of arterial thrombosis following liver transplantation]. PMID- 8211386 TI - [Osteosarcoma of the thyroid gland]. PMID- 8211387 TI - [Conservative therapy of liver injuries in children]. AB - During the 14-year period between 1979 and 1992 the authors treated by conservative methods nine children with liver injuries. They operated on four children. The liver injury did not bleed during operation or haemorrhage was only minimal and probably the patients would have also recovered after conservative treatment. In the discussion the authors mention diagnostic approaches in liver injuries and criteria and methods of conservative treatment. The authors consider conservative treatment of liver injuries in children to be a very suitable method which is associated only with a very small number of complications, and which proves successful in the majority of patients. The prerequisite for its application are high standard of diagnostic visualization methods, monitoring of the child's condition and the possibility of immediate surgery, if conservative treatment fails. PMID- 8211388 TI - [Therapy of diaphyseal fractures of the leg in a district hospital]. AB - During the period between 1987 and 1991 at the surgical department of the Trebic hospital 136 casualties with closed diaphyseal fractures were treated. All patients were older than 18 years and monotraumas were involved. The patients were treated by immobilization by a classical high plaster bandage, functional plaster as recommended by Sarmient, extension treatment, miniosteosynthesis, osteosynthesis using a splint, intramedullary fixation as described by Kuntscher and Simon-Enders-Weidner, or possibly by a combination of the mentioned methods. The author divides fractures of the leg into stable and unstable fractures and fracture with so-called urgently indicated osteosynthesis. The mean period of treatment with high plaster bandage was 31.7 weeks, functional plaster according to Sarmient 20.2 weeks, miniosteosynthesis with plaster fixation 25.5 weeks. When splints were used, the mean period of treatment was 30.5 weeks, in osteosynthesis according to Enders 20.6 weeks. The best results in stable fractures were achieved by functional plaster according to Sarmient, in unstable fractures and those with indicated osteosynthesis by using intramedullary fixation as described by Enders. PMID- 8211389 TI - [Myositis ossificans--a rare complication after axillary dissection]. AB - We are showing a case of the myositis ossificans, appearing after the dissection of axilla simulating a metastasis of a malignant melanoma. In these circumstances this is a very rare case. It can, however, lead to an unnecessary operation. For this reason it should be useful to bera this possibility in mind. PMID- 8211390 TI - [A cosmetic surgery technique for varices in the lower extremities]. AB - The author describes a variant of a cosmetic operation of varicosities of the lower extremities which proved successful in the course of 17 years. The operation was performed in a total of 1823 patients. Minimalization of the size and number of surgical incisions is made possible by the use of very simple instruments comprising an elevator of the saphena magna, strippers for subsidiary varicosities (4 sizes), an applicator of temporary tamponade and two types of chisels for suprafascial and subfascial severing of perforating veins. The number of operations on account of relapses is 9.04% during a representative period in 1990 and 1991. The period of work incapacity is by one week shorter. The cosmetic results are excellent. The instruments and the described technique are at present used in 35 institutes. PMID- 8211391 TI - [Treatment of acetabular fractures. 1. Indications for surgical approaches]. AB - The results of surgical treatment of fractures of the acetabulum depend on the selection of the surgical approach. Therefore the authors focused their attention on the surgical approaches which are best known and used most frequently at present. They present a review and brief characteristic of different surgical approaches. On a group of 70 fractures in the region of the acetabulum they demonstrate their own practical experience with the application of different approaches. Based on their experiences and analysis of data reported in the literature, they submit indications of these approaches when dealing with actual traumatological situations in the region of the injured acetabulum. PMID- 8211392 TI - [Esophageal injuries]. AB - The authors present an analysis of 33 oesophageal injuries treated at the surgical clinic of Faculty Hospital Plzen in 1976-1991. Iatrogenic injuries predominated (a total of 24 cases). Of these seven developed during oesophagoscopy performed on account of dysphagic complaints caused by benign or malignant disease. Ten injuries developed in conjunction with endoscopic extraction of a foreign body, three occurred during operation of hiatus hernia, two during sclerotization of oesophageal varices and one each during insertion of a nasogastric tube and oesophageal endoprosthesis. In the remaining cases perforation occurred during traumatic injury of the neck four times, twice as a result of a swallowed bone, and three perforations were spontaneous. The total mortality was 27.3%. The authors analyze factors which influence the morbidity and mortality--the site of injury, the time which elapsed between injury and treatment, the patient's age, mode of injury, associated diseases and method of treatment. They found that the most frequent complication and most frequent cause of death was septicaemia from mediastinitis and empyema of the chest. PMID- 8211393 TI - [Laparoscopic cholecystectomy and choledocholithiasis]. AB - Laparoscopic operations are a revolution in surgery. So far they were developed most in surgery of the biliary pathways. The authors emphasize the necessity to extend diagnostic and therapeutic examination methods of the biliary pathways pre , intra- and postoperative ERCP, pre- and intraoperative cholangiography, choledochotomy, choledochoscopy, concrement extraction. Only then laparoscopic operations attain their full importance with all advantages--postoperative comfort, reduced period of treatment, hospitalization and convalescence, cosmetic effect. The authors present in the submitted paper their own experience and world wide trends--mainly in the USA and France. PMID- 8211394 TI - [Reoperation in Crohn's disease]. AB - In 1967-1992 at the surgical clinic in Plzen 101 patients were operated with histologically confirmed Crohn's disease. A total of 32 urgent operations were performed. Due to the possibility to provide complete parenteral nutrition from this number during the past 6 years only three patients were operated. During the next and subsequent period 70 patients were reoperated. Relapses occurred most frequently four years after the first operation. As to the extent of resection, the authors agree with the view that 20 cm from the macroscopic borderline of the affection are sufficient without special regard to lymph nodes. Nevertheless it is important to keep in mind that Crohn's disease is a systemic disease and even by radical removal of the affected part this disease cannot be cured by surgery. PMID- 8211395 TI - [Arterial "crossover" reconstruction in ischemic disease of the lower extremities]. AB - The authors present a group of 20 patients where in the course of a 15-year period (1978-1992) a crossover bypass was made to save a lower extremity with advanced ischaemia. Based on their own experience which they compare with results of physicians abroad they submit an analysis of indications for this type of extra-anatomical reconstruction. In the authors' opinion crossover bypasses have their place in reconstruction surgery of the arteries of the lower extremities if they are perceived as extra-anatomical reconstructions and thus are subjects to strict criteria for indication. PMID- 8211396 TI - [Malignant thyroid tumor surgery at the Surgery Clinic of the Medical School Hospital in Pilsen 1987-1991]. AB - At the surgical clinic of the Faculty Hospital in Plzen in 1987-1991 a total of 230 operations of the thyroid gland were performed in 227 patients, incl., 30 operations on account of malignancies in 27 patients. The presented study is focused on malignant diseases. The mean age of the patients was 57.7 years, women predominated. Postoperative complications such as pareses of the recurrent nerve occurred only in one patient. Only one patient died from generalization of thyroid carcinoma. The authors compared the group with a previous clinical study made in 1967-1983 and with the year 1992. In 1992 they proved an increase of benign and malignant thyroid disease. PMID- 8211397 TI - [Osteomyelitis of the ilium and traumatic rupture of a hydronephrotic right kidney imitating acute appendicitis]. AB - The author describes two case-histories of profoundly different diseases which imitated in a similar way the symptoms of acute appendicitis. In both instances the authors had to operate under pressure of the local finding, although in the case of osteomyelitis of the ilium this diagnosis was contemplated before operation. The author draws attention to some specific features of work in developing countries. PMID- 8211399 TI - [Initial experience with transanal endoscopic microsurgery]. AB - The authors present their initial experience with transanal endoscopic microsurgery which they introduced as the first department in the Republic. So far they used the method in 10 patients. The purpose of the present paper is to provide information on the surgical approach to adenomas and carcinomas in the area of the rectum by a new surgical technique. PMID- 8211398 TI - [Diagnosis and therapy of chronic subdural hematoma]. AB - The authors evaluate a group of 72 patients with the diagnosis of chronic subdural haematoma (cSDH). All subdural collections were confirmed on a computer tomograph. Sixty-nine patients were operated by trepanation and drainage into a closed system which was maintained for a maximum of five days. Three patients with a hyperdense CT finding were subjected to extended trepanation or craniectomy with membranectomy. The CT picture made on the 2nd-4th day after operation revealed a persisting subdural collection in 35% of the patients subjected to trephination. The authors were concerned with the problem whether this percentage makes trephination with drainage controversial as the only universal therapeutic method in cSDH. Nevertheless successful reinsertion of the drain (85%) is in favour of trephination although drainage from the first trephination in not always the definite solution. Conversely revision by craniotomy was a failure in 7 patients where the drainage method was not successful. Radical surgery proved useful only in the initial period in patients who despite a chronic course had on CT a hyperdense collection. The influence of the site, volume of collection, lateral overpressure and possibly a subsidiary CT finding could not be proved on a statistically significant scale, therefore the authors did not use these CT markers when selecting surgical intervention. PMID- 8211400 TI - [The importance of perforators in surgical treatment of varices of the lower extremities]. AB - The authors discuss the role of insufficient perforating veins in the surgical treatment of primary varicosities of the lower extremities. They evaluated the frequency and site of insufficient perforating veins in 284 patients, operated in 1989-1991. Insufficient perforating veins were found in 21.8% operated patients. Most frequently insufficiency of perforating veins of Cockett's group was found, i.e. in 77.4%. Patients who were operated on account of a relapse of varicosities had insufficient perforating veins in 38% and in patients with trophic skin changes insufficient perforating veins were found in 78.5%. The haemodynamic role of perforating veins and their importance with regard to relapses of varicosities is discussed. The authors describe their own diagnostic and therapeutic procedure. PMID- 8211401 TI - [Initial experience with the fish-shaped incision in mastectomy]. AB - The authors are showing their early experiences with the modified mastectomy with the use of the fish-shape incision, first published by Nowacki and Towpik in 1988. The fish-shaped incision reduces the amount of the skin in the axilla by adding two triangles on the lateral edge of the incision, prevents the "dog ear" deformity and makes the clearance of the axilla easier. PMID- 8211402 TI - [Peroperative glove damage as a possible risk for the surgical team]. AB - With regard to the relative absence of data in our as well as the world literature on possible peroperative injuries of the surgical team, the authors investigated damage of surgical gloves during operation. They divided operations by types and the structure of the surgical team. It was found that on average 45.5% of the gloves used during operations were damaged. PMID- 8211403 TI - [A pancreatic pseudocyst in the liver]. AB - A large cystic formation in the liver of 43-years old woman was identified as pancreatic pseudocyst, using histologic examination during laparotomy. The pancreas was found quite normal without any relation to the pseudocyst. Therefore it seems to be acceptable such a pathogenetic reflection, that the pseudocyst developed as a result of pathologic changes in heterotopic pancreatic tissue (embryonic malformation). The pseudocyst was partly resected and the large cavity in the liver was drained into the small intestine using Roux loop. After 8 months uncomplicated follow-up of the patient, the CT picture of her liver was nearly normal. PMID- 8211404 TI - [Therapy of bleeding esophageal varices in children--present and future aspects]. AB - The authors' department has devoted the past 25 years to treatment of portal hypertension in children and above all to the most dramatic manifestations haemorrhage from oesophageal varicosities. In previous years a number of surgical and conservative methods was used. The milestone in therapeutic strategy and tactics was the year 1990 when endoscopic sclerotization of oesophageal varices was introduced as a routine method. Since then 14 patients aged 5-17 years were treated. In addition to sclerotization also medicamentous and surgical treatment are used. The authors evaluate their experience assembled during the past three years and recommend optimal procedures in children. They try also to foresee the future development of therapy. PMID- 8211405 TI - [Diaphragmatic relaxation in the neonate]. AB - The author demonstrates 5 children with relaxation of the diaphragm and varying intensity of clinical manifestations, in particular hypoxia. Aetiological and pathogenetic relations in relaxation of the diaphragm are discussed as well as the therapeutic procedure. The problem of early indication of surgical treatment is emphasized. PMID- 8211406 TI - D. J. du Plessis Lecture. The simple surgical audit--benefits and spin-offs of un esoteric research. PMID- 8211407 TI - Asymptomatic carotid artery bifurcation disease in patients with claudication. AB - A study was undertaken to determine the prevalence of asymptomatic atherosclerotic carotid artery bifurcation disease in patients presenting with claudication; thus 263 consecutive patients with intermittent claudication, but without recent or old cerebrovascular symptoms were studied by routine carotid duplex scanning. Of the 263 patients, 124 (47.1%) had a C, D, D+ or E lesion in some vessels of the carotid bifurcation and 54 (20.5%) had a D, D+ or E lesion of the common or internal carotid arteries. Women had a higher prevalence of significant carotid stenosis (29.6% v. 18.2% in men) as did patients over the age of 70 years (28.6% v. 16.3% if below 70 years). It is concluded that the prevalence of clinically significant carotid bifurcation disease (greater than 50% stenosis in the common or internal carotid arteries) in patients with claudication is high (20.5%). The presence of an asymptomatic high-grade stenosis (D+ or E) in 11.8% of patients with claudication should alert the clinician that he is treating a patient who is at a high risk of developing cerebrovascular ischaemic complications. PMID- 8211408 TI - The role of total enteral nutrition in pancreatic disease. AB - Conflicting data have been reported on the use of total enteral nutrition (TEN) in pancreatic disease. TEN was used in 17 patients who were candidates for nutritional support with total parenteral nutrition (TPN). There were 7 patients with internal pancreatic fistulas, 2 with protracted traumatic pancreatitis, 7 with severe alcoholic pancreatitis and 1 with a traumatic pancreatic pseudocyst. The mean inhospital stay was 30 days. Precision LR was administered orally or nasally for a mean of 16 days. Five patients with internal pancreatic fistulas were healed during the initial admission on TEN, 1 required surgery and 1 defaulted from hospital treatment. Nine patients with pancreatitis improved on TEN with resolution of pseudocysts or phlegmons (8 patients); 1 patient required a cystojejunostomy. Three patients who defaulted on TEN and consumed a ward diet had relapse of the pancreatitis, which responded rapidly to re-institution of hyperalimentation. There was no mortality in this group of patients. This preliminary report suggests that TEN may be considered as an alternative to TPN for nutritional support in pancreatic disease. PMID- 8211409 TI - [Surgery of the abdominal aorta in the presence of a horseshoe kidney]. AB - Horseshoe kidney is a rare abnormality that complicates aortic surgery. If recognised in time and treated correctly the morbidity and mortality should not be influenced. Two cases are presented and the literature reviewed. PMID- 8211410 TI - Surgical management of retroperitoneal necrotising fasciitis by planned repeat laparotomy and debridement. AB - Mortality remains high in patients with necrotising fasciitis despite use of modern powerful antimicrobial drug therapy and advances in the care of the critically ill. This is particularly so in patients with intra-abdominal retroperitoneal lesions. While necrotising fasciitis of the integument has been well described, its retroperitoneal (extraperitoneal) location has not been highlighted. Planned repeated laparotomies and debridement have been used in 10 recent patients with only 2 deaths. The initiating incident was caesarean section in 3 patients; perineal sepsis, trauma or intra-uterine death in 2 patients each; and uterine instrumentation to induce early abortion in the remaining patient. All patients received empirical antimicrobial therapy, which was changed when microbial isolates and their sensitivity indicated. Mechanical ventilation support was given to 60% of the patients early on during the illness. All received nutritional supplementation either parenterally or enterally throughout their inhospital treatment. This report focuses on intra-abdominal extraperitoneal necrotising fasciitis and the use of planned repeated laparotomy and debridement in the treatment of retroperitoneal (extraperitoneal) necrotising fasciitis per se and we recommend it as an essential part of the management of this condition. PMID- 8211411 TI - The challenges facing paediatrics and paediatric surgery in India. PMID- 8211412 TI - A critical review of hypopharyngeal carcinomas--1975-1985. AB - Seventy-seven patients with hypopharyngeal carcinomas who presented to Groote Schuur Hospital between 1975 and 1985 are reviewed. Of these patients 76.6%, mostly with pyriform fossa tumours, had advanced disease. The overall 5-year survival was poor (10.5%) despite combined radiotherapy and surgery in many. Local tumour control remains poor and a split course of radiotherapy offers no solution. PMID- 8211413 TI - Singular neurectomy in South African practice. AB - Singular neurectomy was used in intractable or prolonged benign paroxysmal positional vertigo, which was incapacitating in 7 patients. Six patients were cured, 1 patient suffered a severe sensorineural loss and 1 patient a mild-to moderate loss. Singular neurectomy is an effective treatment for this condition. PMID- 8211414 TI - An alternative method of treating comminuted intra-articular fractures of the distal radius. AB - Comminuted intra-articular fractures of the distal radius will inevitably end in poor results if inadequately treated. We recommend an external fixator by two proximal and one distal Steinmann pins incorporated into a short plaster of Paris cast. This distraction method is easy, does not need special instrumentation, and is very cost-effective. Our method differs from previous methods in its simplicity and predictably good results if the recommended technique is followed. PMID- 8211415 TI - A hypermetabolic reaction during anaesthesia and surgery. A case report. AB - A young man underwent anaesthesia and surgery after multiple fractures. After 2 hours of anaesthesia, the patient developed hypercapnia, acidosis, hyperpyrexia and mild muscle rigidity. He was treated for malignant hyperthermia. Muscle tension studies with caffeine-halothane and muscle histology proved normal. The differential diagnosis of this abnormal metabolic response is briefly discussed. PMID- 8211416 TI - Clinical economics. PMID- 8211417 TI - Frozen stored red blood cells and autologous transfusion. PMID- 8211418 TI - Why fibrinogen should be measured as part of the coronary heart disease risk profile. PMID- 8211420 TI - Mind and healing--removing obstacles which have inhibited enquiry. PMID- 8211419 TI - Brains and vitamins. PMID- 8211421 TI - The new psychiatry. PMID- 8211422 TI - The effect of a 6-month cardiac rehabilitation programme on serum lipoproteins and apoproteins A1 and B and lipoprotein a. AB - One hundred and forty-two cardiac rehabilitation patients were followed up over a period of 6 months and the percentage change over time was recorded for various lipid fractions including apoprotein AI (apo AI), apoprotein B (apo B) and lipoprotein a (Lp(a)). Data were analysed to see if improvement in peak oxygen consumption (VO2) or changes in body weight were related to any of the above. A significant percentage change was found for peak VO2, ventilatory threshold, high density lipoprotein cholesterol (HDLC) and triglyceride levels, total cholesterol (TC)/HDL ratio, apo AI, apo A/apo B ratio and Lp(a). Multiple regression analysis showed that alterations in the lipid fractions were not related to changes in physical fitness except in the case of TC levels which dropped independently of other measures. On multivariate analysis, Lp(a) correlated positively with both the Broca index and the use of drugs of the fibrate series. PMID- 8211424 TI - Unsustainability of a measles immunisation campaign--rise in measles incidence within 2 years of the campaign. AB - The 1990 national mass measles immunisation campaign resulted in a marked reduction in measles incidence in Natal/KwaZulu in the first 6 months after the campaign. Data from the measles ward admissions book at Clairwood Hospital were collated for the period 1 January 1989 to 31 May 1992 to assess the sustainability of the effects of the campaign. For the first 12 months after the campaign, measles admissions were consistently low. Thereafter, the number increased steadily, rising sharply to above pre-campaign levels 21 months after the campaign. The age distribution of measles patients indicated that the initial fall in the 10-12-month age group had been reversed in the second year after the campaign, suggesting that the high vaccination coverage achieved for this age group during the campaign had not been maintained. Measles admissions to Clairwood Hospital indicate that the effect of the measles immunisation campaign has not been sustained and that urgent action is required to avert a possible epidemic. PMID- 8211423 TI - The prevalence of antiphospholipid antibodies in women with reproductive failure or major abruptio placentae. AB - The so-called antiphospholipid syndrome may be responsible for repeated spontaneous abortion and fetal loss. We examined the plasma of 61 women with either reproductive failure or abruptio placentae for the presence of lupus anticoagulant and anticardiolipin antibodies in an attempt to assess the prevalence of this condition. No patient had haematological abnormalities consistent with the presence of lupus anticoagulant. However, 6 women had anticardiolipin antibodies with normal coagulation tests. The clinical profile together with this laboratory finding allows us to diagnose the antiphospholipid syndrome in these patients. Our incidence is considerably lower than that reported in many other studies but does suggest a place for screening for this condition in patients with recurrent complications of pregnancy. PMID- 8211425 TI - The role of private hospitals in South Africa. Part II. Towards a national policy on private hospitals. AB - This paper reviews some aspects of present state policy on private hospitals and sets out broad policy guidelines, as well as specific policy options, for the future role of private hospitals in South Africa. Current state policy is reviewed via an examination of the findings and recommendations of the two major Commissions of Inquiry into the role of private hospitals over the last 2 decades, and comparison of these with the present situation. The analysis confirms that existing state policy on private hospitals is inadequate, and suggests some explanations for this. Policy options analysed include the elimination of the private hospital sector through nationalization; partial integration of private hospitals into a centrally financed health care system (such as a national health insurance system); and the retention of separate, privately owned hospitals that will remain privately financed and outside the system of national health care provision. These options are explained and their merits and the associated problems debated. While it is recognised that, in the long term, public ownership of hospitals may be an effective way of attaining equity and efficiency in hospital services, the paper argues that elimination of private hospitals is not a realistic policy option for the foreseeable future. In this scenario, partial integration of private hospitals under a centrally financed system is argued to be the most effective way of improving the efficiency of the private hospital sector, and of maximising its contribution to national health care resources. PMID- 8211426 TI - Equity versus humanity in health care. AB - When the distinction between subjective value judgements and objective scientific analysis becomes blurred, the resulting confusion of values can result in the treatment of economic symptoms rather than causes. Advisors who confuse egalitarianism with humanitarianism may falsely believe they are helping the poor when, instead, they are only promoting equality: the two are not the same. Statistical studies on the distribution of health care provision do not lead to self-evident policy conclusions. PMID- 8211427 TI - Neurocysticercosis--experience at the teaching hospitals of the University of Cape Town. AB - In the 15 years 1975-1989, 239 patients attending the associated teaching hospitals of the University of Cape Town have been identified retrospectively as having neurocysticercosis. One hundred and twenty-three (51.46%) were children 12 years of age or younger, 14 (5.86%) were adolescents aged 13-19 years, and 102 (42.68%) were adults 20 years of age or older. Two hundred and twelve (88.7%) of these patients were black, almost exclusively Xhosa-speakers originating from the eastern Cape homeland regions of Transkei and Ciskei. Although the clinical features of neurocysticercosis are protean, these patients could be divided into three clinicoradiological groups--a group with seizures, a group with raised intracranial pressure, and an asymptomatic group. One hundred and ninety patients (79.5%) presented with seizures, either alone or in combination with other neurological deficits. Eighty-six patients (36%) presented with features of raised intracranial pressure, due to hydrocephalus in 32 cases, to focal space demanding lesions in 4 and to multifocal cysticercal encephalitis in 50. Of interest is the significant difference in the abnormality causing the raised intracranial pressure in the children as opposed to the adults--44 children had multifocal cysticercal encephalitis while only 6 had hydrocephalus, and 26 adults had hydrocephalus while only 6 young adults (including 2 adolescents) had multifocal encephalitis. In the other 4 adults the raised intracranial pressure was caused by space-demanding mass lesions. Ten adult patients (4.1%) were 'asymptomatic' and a computed tomography scan for investigation of head injury revealed neurocysticercosis. PMID- 8211428 TI - Placebo substitution for methyldopa in geriatric hypertensive patients. AB - The aim of this study was to obtain an objective evaluation of the possibly inappropriate antihypertensive therapy of elderly patients; this was done by means of placebo substitution for methyldopa, one of the drugs taken by all the participating patients. Forty patients were recruited from a hospital outpatient clinic and randomly allocated to two groups. One group remained on treatment which included methyldopa, while a matching placebo tablet was substituted in the other group. The study was conducted over a period of 6 months in a single-blind manner. Methyldopa was reintroduced in the placebo group when one of the evaluation clauses was recorded. Only 2 patients in the placebo group required reintroduction of methyldopa tablets. In the rest of this group there was no significant difference between systolic and diastolic pressures before and after 6 months of placebo substitution. Withdrawal of unnecessary antihypertensive therapy in the elderly should be considered. Patients must be observed carefully and therapy reintroduced when blood pressures rise. PMID- 8211429 TI - A South African outpatient drug treatment centre. AB - The Cape Town Drug Counselling Centre is an outpatient drug treatment service which has been operational since 1985. Statistics obtained from 1990 are detailed, describing patient characteristics in respect of referral sources, age, sex, occupational status, educational level and drugs abused. The typical client profile that emerges is of a young employed male of limited education, referred from a non-professional source, who smokes cannabis alone or with methaqualone (Mandrax). Management of clients, which includes psychotherapy with an emphasis on group-work and medical intervention, is described, and proposed areas for further research are outlined. PMID- 8211430 TI - The incidence and nature of injuries in first-league and provincial cricketers. AB - This study investigated the incidence and nature of injuries sustained by club and provincial cricketers during a season. Questionnaire responses were obtained from 183 (59%) of 308 cricketers canvassed. The overall seasonal incidence of risk of injury in all players was 49.1% and this was higher for provincial cricketers (71.6%). The single most common site of injury was the fingers (20.5%). The seasonal incidence of injuries in bowlers (42%) and fielders (40.9%) was higher than in batsmen (17.1%). Young players (< 26.2 years) sustained more injuries than older players. The majority of injuries occurred during matches (69.3%), particularly near the beginning and the end of the season. Furthermore, 23.9% of the injuries were recurrent injuries from the previous season and 22.7% of injuries sustained recurred during the season. Cricket injuries have not yet reached serious proportions, but all involved need to be aware of their incidence and nature. PMID- 8211431 TI - Risk factors for uveitis in sarcoidosis. AB - Uveitis is a potentially sight-threatening complication of sarcoidosis. The object of this study was to determine which patients with sarcoidosis are at greater risk of developing uveitis. We retrospectively assessed 136 patients with clinical, radiological and histological features of sarcoidosis. Of the 48 patients (35.3%) with signs of intra-ocular inflammation, 28 had anterior uveitis, 2 had posterior uveitis and 18 had signs of panuveitis. When patients with uveitis were compared with patients without ophthalmic involvement, no significant demographic, clinical or laboratory differences were found. On linear discriminant analysis, however, the presence of ocular inflammation could be predicted in 32 out of 48 patients (66.6%); age at diagnosis and an elevated serum calcium level were relative risk factors. Awareness of the high incidence of uveitis and education of those at greater risk may result in earlier diagnosis and treatment of ocular inflammation. PMID- 8211432 TI - Self-medication in three Orange Free State communities. AB - A study on self-care among whites, blacks and coloureds also focused on different forms of self-medication, including non-compliance. Large differences were found in the self-medication behaviour of the three groups. Different correlates of non compliance were explored, but self-medication was not found to be a substitute for formal medical care. PMID- 8211433 TI - Gender reassignment surgery for male primary transsexuals. AB - This article describes certain innovations and aspects of surgical technique together with some surgical assessments of results in a series of 58 operations for gender reassignment undertaken by the author over the past 24 years. The salient new features described are: (i) to prevent the early and late vaginal contractures that commonly follow previously accepted methods of neo-vagina construction, the technique of dissecting a new vaginal canal has been improved, and an improved skin graft (double-layered) is added to the peno-scroto-perineal flaps used to line the vaginal canal--these split-skin grafts, superimposed upon a meshed thick dermal graft, do not contract nearly as much as solitary split skin grafts; (ii) the vagina is suspended laterally by the testicular cords, threaded above the superior pubic rami; and (iii) repeated intermittent use of a vaginal vibrator is substituted for an indwelling vaginal mould, resulting in better compliance and a more pliable vagina. PMID- 8211434 TI - Alpha-galactosidase A deficiency (Fabry's disease) in a black Zimbabwean. AB - We describe a patient with Fabry's disease with renal and myocardial involvement. He has been followed up for 10 years. This metabolic defect has not been noted before in southern Africa; the clinical course is similar to that of western European and American cases. PMID- 8211435 TI - The contributions of J. C. Boileau Grant to the teaching of anatomy. AB - J. C. B. Grant (1886-1973) as been hailed as one of the greatest teachers of anatomy in the English language. Except for those who attended his lectures at Manitoba, Toronto and Los Angeles, his reputation rests on three textbooks, the first editions of which he produced between 1937 and 1943 and which, collectively, have run to 30 editions. Salient aspects of Grant's life and of these three fine books are reviewed and appraised and, unusually in modern times, tribute is paid to him as a writer, not of research works, but of textbooks. PMID- 8211436 TI - Determinants of public opinion about tobacco tax increases. PMID- 8211437 TI - Guidelines for the management of HIV/AIDS. PMID- 8211438 TI - Guidelines for the management of HIV/AIDS. PMID- 8211439 TI - The effect of o-chlorobenzylidene malononitrile (tear gas) on the polymerase chain reaction. PMID- 8211440 TI - Effects of captopril and prazosin on renal function in diabetes. PMID- 8211441 TI - Severity of fetal haemolysis in different racial groups in relation to predelivery anti-D (rhesus) titres. PMID- 8211442 TI - Caudal epidural morphine in children--a need for caution! PMID- 8211443 TI - Preventing malaria. PMID- 8211444 TI - Preventing malaria. PMID- 8211445 TI - Clinical experience with epidural buprenorphine for analgesia. PMID- 8211446 TI - Prevention of congenital syphilis. PMID- 8211447 TI - The rapid laboratory diagnosis of tuberculosis. PMID- 8211448 TI - Hunger strikers--ethical and management problems. PMID- 8211449 TI - [Artificial insemination with donor semen]. PMID- 8211450 TI - Occurrence of Fusarium moniliforme and fumonisins in maize in relation to human health. PMID- 8211451 TI - Honouring the prophets. PMID- 8211452 TI - Brain death and organ transplantation--an Islamic opinion. PMID- 8211453 TI - Sulphur dioxide sensitivity in South African asthmatic children. AB - Sulphur dioxide (SO2) is a well-known precipitant of asthmatic attacks. Many foodstuffs are preserved with SO2 and other sulphites. In this study 37 asthmatic children attending the Allergy Clinic at the Red Cross Children's Hospital were challenged with SO2 in apple juice in a dose similar to that commonly ingested in soft-drinks containing this preservative. The responses of these children were compared with the responses of 22 asthmatics challenged with apple juice alone. Sixteen out of 37 children (43.2%) challenged with SO2 reacted with a fall in forced expiratory volume in 1 second (FEV1) of more than 10% compared with none of the 22 control asthmatic children challenged with apple juice alone (P = 0.0016). Girls were found to be more sensitive than boys. A 20% or more fall in FEV1 occurred in 8 (21.6%) of the children challenged with SO2 compared with none in the control group (P = 0.039). There was an individual variability in the responses of sensitive individuals to the SO2 challenge. Reactions occurred in spite of maintenance medication and occurred within 5-30 minutes of challenge. Since sulphite sensitivity is common in asthmatic children, ingestion of sulphites should be avoided. PMID- 8211454 TI - Voluntary total fasting in political prisoners--clinical and biochemical observations. AB - Thirty-three political prisoners on hunger strike (voluntary total fast--VTF) for 6-24 days were admitted to two hospitals in Johannesburg in 1989. They had been detained without trial for 4-32 months. Sound doctor-patient relationships were established by emphasis of the principle of full patient participation in clinical decision-making at every level, by rejection of police interference in patient care, and by refusal to discharge subjects back into detention. Depression and abdominal pains were the predominant symptoms. In 6 lean subjects with complete data the expected initial period of rapid weight loss was not observed. Before hospitalisation most subjects became dehydrated from inadequate fluid intake and an apparent absence of thirst. Serum creatinine concentrations were a better indication of dehydration than serum urea levels. Mild hyponatraemia was found in one-third of patients. Refeeding after 6-27 days of VTF was initiated with a dilute lactose-free formula diet, and was uncomplicated. Close clinical monitoring of subjects during VTF is essential, and it is recommended that prisoners should be admitted to hospital at 10% of weight loss, if not before. The health care of prisoners can best be provided by professionals independent of the police and prison services. PMID- 8211455 TI - Drug and poison information--the Tygerberg experience. AB - This report is based on an analysis of 6,411 consultations processed by the Tygerberg Pharmacology and Toxicology Consultation Centre. Seventy-five per cent of the consultations were of a toxicological nature: 47% related to non-drug chemicals, 37% to drugs and 16% to plants and animals. Pesticides utilised in the home environment featured most prominently in the non-drug chemical group, while queries about paracetamol overdose topped the list in the drug group. The most frequent queries in the biological category concerned potentially poisonous plants. Twenty-five per cent of the consultations related to pharmacotherapeutics. Most potentially toxic exposures to non-drug chemicals occurred in the household setting. Contrary to popular belief, few acute pesticide poisonings were encountered as a result of exposures during farming activities. Another important finding was that there is a frustrating lack of reliable and readily available information in respect of potentially toxic ingredients contained in household and industrial preparations. The large number of household exposures high-lights the need for education in the safe storage and usage of non-drug chemicals. Legislation on the inclusion of basic toxicological information and warnings on labels of household and industrial non-drug chemical products should be considered. In addition, the Government should take responsibility for centralizing information on all potentially toxic non-drug chemicals and make this information available to poison centres at all times. It is also imperative that more attention be given to the training of health care professionals in applied pharmacokinetics and toxicology. PMID- 8211456 TI - Black and brown widow spider bites in South Africa. A series of 45 cases. AB - Cases of black widow (Latrodectus indistinctus) and brown widow (L. geometricus) spider bites referred to the Tygerberg Pharmacology and Toxicology Consultation Centre from the summer of 1987/88 to the summer of 1991/92 were entered into this series. Of a total of 45 patients, 30 had been bitten by black and 15 by brown widow spiders. It was evident that black widow spider bites caused a more severe form of envenomation than brown widow bites, characterised by generalised muscle pain and cramps, abdominal muscle rigidity, profuse sweating, raised blood pressure and tachycardia. The symptoms and signs of brown widow bites were mild and tended to be restricted to the bite site and surrounding tissues. Conditions which should be considered in the differential diagnosis include cytotoxic spider bite, scorpion sting, snakebite, acute abdominal conditions, myocardial infarction, alcohol withdrawal and organophosphate poisoning. To prevent the development of complications, the administration of black widow spider antivenom is recommended in severe cases because untreated latrodectism could become protracted, without improvement, for several days. PMID- 8211457 TI - Scorpionism in South Africa. A report of 42 serious scorpion envenomations. AB - Forty-two cases of serious scorpion envenomation, of which 4 had a fatal outcome, are presented. The clinical profile, differential diagnosis and management of scorpionism are discussed. Most envenomations occurred in the summer months, peaking in January and February. An immediate local burning pain was the most prominent symptom. Systemic symptoms and signs developed within 4 hours of the sting in most instances, characterised by general paraesthesia, hyperaesthesia, muscle pain and cramps. Other striking features included dysphagia, dysarthria and sialorrhoea with varying degrees of loss of pharyngeal reflexes. The blood pressure and the temperature were often raised and the tendon reflexes increased, while motor power was often impaired. In a considerable number of patients the course was complicated by varying degrees of respiratory dysfunction, which tended to be more serious in children. The oustanding feature in children was an extreme form of restlessness characterised by excessive neuromuscular activity. Victims of scorpion sting, particularly in high-risk localities, should be closely observed for 12-24 hours. Children and other high-risk patients should be hospitalised. All patients with symptoms and signs of systemic envenomation should receive antivenom. Parabuthus granulatus (Hemprich & Ehrenberg, 1828) has been identified as the most important venomous species in the western Cape. The antivenom is produced from the venom of the medically less important P. transvaalicus Purcell, 1899. A strong case can therefore be made for the inclusion of P. granulatus venom in the production of a polyvalent antivenom. PMID- 8211458 TI - Port-a-caths in cancer patients. AB - We report on 91 patients with cancer who underwent the insertion of 89 venous and 4 hepatic arterial, implanted vascular ports (Port-a-caths) for periods of up to 33 months (total 1,525 patient-months). There were 1 fatal, 9 serious and 8 minor complications in 18 patients which are described and discussed. In this series, complications were more common in younger patients, and infection was rare. Port a-caths are extremely useful for vascular access, and have a low complication rate. However, the occasional occurrence of serious and even fatal complications suggests that the decision to insert a device should be judiciously weighed. PMID- 8211459 TI - The 'economics' of medical technology. AB - The word 'economics' is used in this paper in its widest sense, referring to issues that 'influence the management, regulation and government of an enterprise'. In addition to the obvious monetary issues in health-care technology, social, ethical, legal and cultural issues are also discussed. The eventual, generally high cost of health care is definitely influenced to a greater or lesser extent by these factors. It is suggested that proper evaluation during the planning stage could lead to the development and introduction of technologies into health care in a more cost-effective way. PMID- 8211460 TI - Cost escalation in health-care technology--possible solutions. AB - Solutions to cost escalation due to health-care technology are proposed. It is argued that proper systems analysis, technology assessment, and planning would result in net savings and improved cost-benefits. Identification of needs early in the technological life cycle can positively influence the final form of the chosen technology. A national centre for technology assessment is proposed. Arguments in favour of a local medical equipment manufacturing industry, emulating overseas examples, are advanced, appropriateness being the main criterion. Analysis of the cost breakdown of imported technology suggests ways of reducing costs considerably, while stimulating the local economy. Digital telecommunications technology and its application to rural health care is cited as an example of a potentially worthwhile investment in making overall coverage more equitable. PMID- 8211461 TI - Traditional healers and AIDS prevention. AB - A qualitative case study of the views and experiences of an isangoma was undertaken to explore potential preventive health roles that traditional healers could play with regard to the AIDS epidemic. The isangoma's knowledge of the transmission mechanisms, risk groups and prevention strategies for AIDS was accurate. Her questionable beliefs included a Nazi conspiracy as the source of AIDS, a string ritual to prevent promiscuity and a conviction that she could treat AIDS. Notwithstanding the latter beliefs, her generally factual knowledge of AIDS indicated that she could be an important source of AIDS information in the community; she was, in fact, already providing some AIDS counselling. Considering their large clientele, established preventive health ethic, extensive distribution in rural areas and potential ability to influence the contextual factors that affect risk-reducing behaviours (e.g. condom use), it is recommended that traditional healers be incorporated into AIDS prevention programmes where they can play a role in community-based AIDS education and condom promotion. PMID- 8211462 TI - The areca nut chewing habit and oral squamous cell carcinoma in South African Indians. A retrospective study. AB - A retrospective study (1983-1989) of oral squamous carcinomas and concomitant oral habits was undertaken in South African Indians from Natal. Information came from hospital records and interviews with patients, families and friends. There were 143 oral squamous carcinomas; these occurred in a ratio of 1:1,6 for men and women respectively. Squamous carcinomas of the cheek (buccal mucosa, alveolar sulcus and gingiva) occurred most frequently, especially in women (57/89--64%), while in men tongue cancer predominated (22/54--41%). Ninety-three per cent of women (83/87) and 17% of men (9/54) habitually chewed the areca nut. Thirty-nine of 57 women (68%) with cheek cancer and 21/25 (84%) with tongue cancer only chewed the nut (no tobacco, snuff or smoking). Analyses confirmed an association between nut chewing and cheek cancer. The odds ratio (OR) for oral cancer in women 25 years and older who only chewed the nut was 43,9 and the attributable risk (AR) 0,89 (89%). With tobacco the OR increases to 47,42 and the AR to 0,91 (91%). The data showed that the areca nut habit with or without tobacco use is important in the development of oral squamous carcinoma. Elimination of this habit can reduce the risk in these women substantially (89-91%) if all other factors remain the same. PMID- 8211464 TI - Treatment of tuberculosis in patients with pre-existing liver disease or following hepatotoxic drug reactions. PMID- 8211463 TI - Kaposi's sarcoma after alpha-interferon treatment for HIV-negative T-cell lymphoma. AB - A 54-year-old HIV-negative patient suffering from T-cell lymphoma of Lennert's lymphoma (Lel) type was treated for 13 months with interferon alpha-2b. While on treatment with interferon the patient demonstrated suppression of total and CD4+ lymphocytes to levels < 0,5 and 0,2 x 10(9)/l, respectively. Although interferon was successful in controlling the lymphoma the clinical course was complicated by the rapid development of aggressive, fatal Kaposi's sarcoma shortly after cessation of interferon treatment. It is suggested that the immunosuppressive effect of interferon therapy (or the T-cell lymphoma or both) may have played a role in the development of Kaposi's sarcoma as a second malignancy. PMID- 8211465 TI - 'Map and zap'--electrode catheter techniques for treatment of supraventricular tachycardias. PMID- 8211466 TI - Occupational lung disease. PMID- 8211467 TI - Early control of malaria epidemics in Natal and Zululand. PMID- 8211468 TI - Umbilical endometriosis. PMID- 8211469 TI - Are the department's reasons for not making AIDS notifiable adequate? PMID- 8211470 TI - The reverse Esmarch bandage for venous access. PMID- 8211471 TI - Medical care in Lebowa--resources are being wasted! PMID- 8211472 TI - Possible false-positive results for parvovirus B19 IgM antibodies. PMID- 8211473 TI - The traditional healer and our future health system. PMID- 8211474 TI - Depot flupenthixol-induced mania. PMID- 8211475 TI - Para-occupational lead poisoning in Soweto. PMID- 8211476 TI - [Distribution routes of insulin secretion granules]. PMID- 8211477 TI - Antiphospholipid antibodies in South Africa blacks with connective tissue diseases--more evidence for an 'aPL-negative coagulopathy'? PMID- 8211478 TI - Inappropriate antenatal care. PMID- 8211479 TI - Adolescent health in South Africa--urgent action needed. PMID- 8211480 TI - Academic health complexes--ivory towers or national resources? PMID- 8211481 TI - Transforming national health policy. A response to the initiative of the Department of National Health and Population Development. PMID- 8211482 TI - Risk-taking behaviour of Cape Peninsula high-school students. Part I. Introduction and methods. AB - In this study, risk-taking behaviour of Cape Peninsula high-school students was investigated. Suicidal behaviour, cigarette smoking, alcohol consumption, drug use, road-related behaviour, violent behaviour and sexual behaviour were included. This article, the first in a series, describes the rationale and methodology of the project. Sixteen schools were selected so as to yield a representative sample of schools in the three major education departments in the Cape Peninsula (administered by the Department of Education and Training and the Houses of Assembly and Representatives). The final sample size was 7,340 school students. A self-administered questionnaire was completed in a normal school period. Estimates for each education department were weighted to produce an overall estimate. The results are presented by standard and home language(s), and gender. Limitations of the study include its cross-sectional nature; the possibility of under- and over-reporting; the exclusion of important groups of adolescents such as absentees and dropouts, and those attending specialised and private schools; and not being able to present the results separately for each education department. PMID- 8211483 TI - Risk-taking behaviour of Cape Peninsula high-school students. Part II. Suicidal behaviour. AB - The prevalence of a wide range of risk-taking behaviour among high-school students in the Cape Peninsula, South Africa, was investigated. In this article, the results for suicidal behaviour are presented. Cluster sampling techniques produced a sample of 7,340 students from 16 schools in the three major education departments. A self-administered questionnaire was completed in a normal school period. Estimates for each education department were weighted to produce an overall estimate. During the previous 12 months, 19% of students had seriously thought about harming themselves in a way that might result in their death, 12.4% had told someone that they intended to put an end to their life, and 7.8% had actually tried to put an end to their life. There were different trends according to gender, standard and language(s) spoken at home. Of those who had made a suicide attempt during the previous 12 months, 85.7% indicated that they had seriously thought about doing so, while 57.7% had told someone that they intended putting an end to their life. There is in many cases no continuity from suicidal ideation to communicating suicidal intent to an actual attempt. PMID- 8211484 TI - Risk-taking behaviour of Cape Peninsula high-school students. Part III. Cigarette smoking. AB - The prevalence of a wide range of risk-taking behaviour among high-school students in the Cape Peninsula, South Africa, was investigated. In this article, the results for cigarette smoking are presented. Cluster sampling techniques produced a sample of 7,340 students from 16 schools in the three major education departments. A self-administered questionnaire was completed in a normal school period. Estimates for each education department were weighted to produce an overall estimate. Of the students 18.1% indicated that they smoked at least 1 cigarette per day. Of these, 66.9% had tried to stop. Of those who did not smoke at least 1 cigarette per day, 41.2% had smoked previously and 3.6% intended to start smoking. There were different trends according to gender, standard, and language(s) spoken at home. Of note was the small percentage of Xhosa-speaking females who smoked. There is an urgent need for smoking prevention programmes in schools. PMID- 8211485 TI - Risk-taking behaviour of Cape Peninsula high-school students. Part V. Drug use. AB - The prevalence of a wide range of risk-taking behaviour among high-school students in the Cape Peninsula, South Africa, was investigated. In this article, the results for drug use are presented. Cluster sampling techniques produced a sample of 7,340 students from 16 schools in the three major education departments. A self-administered questionnaire was completed in a normal school period. Estimates for each education department were weighted to produce an overall estimate. Cannabis was the illicit drug most widely used; 7.5% had smoked cannabis, and 2.4% had done so in the previous 7 days. A small subgroup (1.6%) of students had smoked cannabis and methaqualone (Mandrax) together. Reported lifetime use of injectable drugs was 0.5%, and 10.9% had sniffed solvents, 2.6% having done so in the previous 7 days. There were different trends according to gender, standard, and language(s) spoken at home. Of particular note was the small proportion of Xhosa-speaking females who were involved with drug use. The results suggest that the majority of drug use among school students is experimental. A small number of adolescents abuse drugs and are at risk for its associated problems; intervention is indicated for this group. PMID- 8211486 TI - Risk-taking behaviour of Cape Peninsula high-school students. Part VI. Road related behaviour. AB - The prevalence of a wide range of risk-taking behaviour among high-school students in the Cape Peninsula, South Africa, was investigated. In this article, the findings for road-related behaviour are presented. Cluster sampling techniques produced a sample of 7,340 students from 16 schools in the three major education departments. A self-administered questionnaire was completed in a normal school period. Estimates for each education department were weighted to produce an overall estimate. During the previous year, 8.5% of the students had been involved in a motor vehicle accident, and 7.4% had been injured in a pedestrian accident. Of those who had driven a vehicle, 63.2% reported driving without a licence; 16.1% drove an overcrowded vehicle; and 8% reported driving under the influence of alcohol or cannabis. Of those who had been on a motorcycle, 47.9% reported riding without a helmet. Despite the availability of seat belts, 37.3% had failed to wear one on the last occasion they were in the front seat of a vehicle. Variations according to gender, standard, and home language(s) were identified. The prevalence of risk behaviour was higher in males, who also showed a more pronounced increase in such behaviour with age. The need for accident prevention programmes remains urgent. PMID- 8211487 TI - Risk-taking behaviour of Cape Peninsula high-school students. Part VII. Violent behaviour. AB - The prevalence of a wide range of risk-taking behaviour among high-school students in the Cape Peninsula, South Africa, was investigated. In this article, the results for violent behaviour are presented. Cluster sampling techniques produced a sample of 7,340 students from 16 schools in three major education departments. A self-administered questionnaire was completed in a normal school period. Estimates for each education department were weighted to produce an overall estimate. Of the total sample, 12.7%, 9.6% and 13.8% reported that they had been physically injured by another person at school, at home and in other settings, respectively; 11.0% had injured another person during the previous year; 5% had committed an act of vandalism; and 9.8% of males and 1.3% of females had carried knives at school. Other trends according to gender, school standard, and home language were identified. Males were more likely to be the perpetrators and victims of violent behaviour; for both genders the extent of victimization decreased with increasing standard; and fewer Xhosa-speaking students than students in other language groups perpetrated incidents of violent behaviour. The potential for intervention programmes is assessed in a context where much violence is determined by sociopolitical factors. PMID- 8211488 TI - Risk-taking behaviour of Cape Peninsula high-school students. Part VIII. Sexual behaviour. AB - The prevalence of a wide range of risk-taking behaviour among high-school students in the Cape Peninsula, South Africa, was investigated. In this article, the results for sexual behaviour are presented. Cluster sampling techniques produced a sample of 7,340 students from 16 schools in the three major education departments, of whom 79.7% answered the section dealing with sexual behaviour. A self-administered questionnaire was completed in a normal school period. Estimates for each education department were weighted to produce an overall estimate. Of the sample, 17.4% indicated a previous episode of heterosexual intercourse. The median age at first intercourse was 15.1 years. The median number of partners in the previous 12 months was 1.0. The median number of weeks since the most recent coital episode was 6.6; on this episode 76.6% had known their partners for more than 7 days, while 60.5% had done something to avoid pregnancy. The most frequently used method of contraception was injectable steroids for Xhosa-speaking students and condoms for the other students. Males and Xhosa-speaking students appear to be particularly at risk for the adverse consequences of sexual activity. The HIV epidemic has increased the urgency of introducing meaningful sexuality education in South African schools. PMID- 8211489 TI - Erythrocyte sedimentation rate in elderly blacks. AB - This study investigated the erythrocyte sedimentation rate (ESR) in an elderly population with the objective of establishing reference ranges and the diagnostic value of the ESR. Elderly blacks were randomly selected from communities in the Orange Free State. ESR determinations were done according to the Westergren method. Total protein, albumin, immunoglobulin and C-reactive protein (CRP) levels were measured on serum. Results were analysed by means of non-parametric statistical methods. In the group with normal CRP' and immunoglobulin levels it was found that 99% of values were below 44 mm/h for men and 62 mm/h for women. The sensitivity and specificity for these cut-off values (CRP used as 'gold standard') were 33% and 91% respectively for men and 75% and 89% respectively for women. PMID- 8211490 TI - Introducing a patient-controlled analgesia-based acute pain relief service into southern Africa--the first 10 months. AB - The 10 months after the introduction of the first acute pain relief service (APRS) in southern Africa is described. Seven hundred patients were treated with morphine by means of patient-controlled analgesia (PCA), administered to patients after major surgery or extensive burns via the intravenous (IV) or subcutaneous (SC) route. The efficacy, safety and resource implications were assessed. The results showed that pain control was good, with the majority of patients (66%) experiencing mild pain during the first 24 hours. The pump was used by each patient for an average of 4.32 days. The mean total dose of morphine used was 105.2 mg via the IV route and 114.6 mg via the SC route. Over the 10 months, the 25 PCA pumps worked 80,000 pump-hours; only 3 pumps malfunctioned. A total of 86,861 mg morphine was used during this period with rare morbidity and no mortality. Only 1 patient experienced sedation and respiratory depression. The benefits of an APRS with PCA to patients and medical staff alike are discussed. PMID- 8211491 TI - Primary and secondary infection with human parvovirus B19 in pregnant women in South Africa. AB - A study of human parvovirus B19 infection in 1,967 pregnant women of all races in Johannesburg revealed an overall prevalence of 24.9% for IgG antibodies and 3.3% for IgM antibodies. Of the 64 IgM-positive sera indicating active infection, 62 were resistant to urea denaturation. No differences in the prevalence of IgG antibodies between population groups were observed, but active infections, as demonstrated by IgM antibodies, were significantly more prevalent in black than in white, coloured or Asian mothers. PMID- 8211492 TI - Pathophysiological mechanisms of urbanisation-related hypertension and the sodium pressor response in black Zimbabweans. AB - This study examined the role of endothelin (ET), the thromboxane A2 (TXA2) prostacyclin (PGI2) ratio (TXA2/PGI2), plasma renin activity (PRA) and urinary aldosterone excretion (ALDO) in urban hypertensive patients and in the sodium pressor response in normotensives. Twenty-seven urban hypertensive patients and the same number of normotensive controls were studied on baseline diet, after 5 days of sodium restriction and after 5 days of sodium loading. Mean arterial blood pressure, plasma and ET values, PRA, TXA2/PGI2 and ALDO were assessed on each diet. The results showed that baseline PRA was suppressed in the hypertensive patients; this indicates that urbanisation-related hypertension is of the low renin type. ET levels and TXA2/PGI2 were higher in hypertensive than in normotensive subjects, suggesting an association between high blood pressure and these factors. Although the baseline PRA in hypertensives was suppressed, urinary ALDO was no different from that in the normotensive controls where PRA was normal. In addition, sodium restriction did not increase PRA in hypertensive subjects while it more than doubled it in the controls. However, ALDO in hypertensive patients increased to levels that were no different from those in the normotensive subjects. Sodium loading increased blood pressure, ET values and TXA2/PGI2 indicating an association between the latter two factors and the sodium pressor response in those with hypertension. ALDO decreased to similar levels on sodium loading in the two groups. This decrease in ALDO was accompanied by suppression of PRA only in normotensive subjects. In conclusion, the low-renin activity urban hypertensives we studied had increased baseline ET levels and TXA2/PGI2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8211493 TI - Serum CA 125 concentrations in women with endometriosis or uterine fibroids treated with gonadotrophin-releasing hormone agonist analogues. AB - We assessed the possible role of CA 125 in the monitoring of gonadotrophin releasing hormone (GnRH) agonist analogue therapy in women with endometriosis and uterine fibroids. Serum concentrations of this cell surface antigen did not correlate with uterine volume and appeared to have no value in the assessment of shrinkage of uterine fibroids during GnRH agonist treatment. While CA 125 levels were not always elevated in subjects with endometriosis, they fell during treatment in all patients. The change accurately reflected therapeutic progress in these women and was of particular value in those patients who had commenced therapy with elevated levels. It is suggested that CA 125 may be useful in the monitoring of therapeutic progress in selected patients with endometriosis treated with GnRH agonists; the need for surgical follow-up may be obviated. PMID- 8211494 TI - Polymerase chain reaction in cancer diagnosis. PMID- 8211495 TI - Human papillomavirus DNA in aerodigestive squamous carcinomas demonstrated by means of in situ hybridisation. AB - A series of 10 oesophageal and 10 laryngeal squamous carcinomas was examined by means of immunocytochemistry and in situ DNA hybridisation to demonstrate human papillomavirus (HPV) infection. Changes in the epithelium adjacent to the carcinoma were found in 5 of 10 oesophageal and 7 of 10 laryngeal carcinomas. Viral antigens could not be detected with immunocytochemistry in any of the specimens. HPV 6, 11 and 16 were detected in 3 oesophageal specimens. In one of these, HPV 16 was detected in normal as well as malignant cells. HPV 7 was detected for the first time in a laryngeal carcinoma. Our results confirm previous reports of possible HPV involvement in the pathogenesis of aerodigestive carcinomas. PMID- 8211496 TI - Neurological Association of South Africa, Annual Congress. Rustenburg, 18-21 March 1993. Abstracts. PMID- 8211497 TI - Magnetic resonance imaging in neurocysticercosis. PMID- 8211498 TI - HIV-2 at Ga-Rankuwa Hospital. PMID- 8211500 TI - The stigma of mental illness. PMID- 8211499 TI - Prostaglandins in the termination of mid-trimester pregnancy. PMID- 8211501 TI - Anomalous left postrenal inferior vena cava. PMID- 8211502 TI - Suction v. conventional curettage in incomplete abortion. PMID- 8211503 TI - Desmoids don't die. PMID- 8211504 TI - Pure red cell aplasia--antilymphocyte globulin-mediated remission. PMID- 8211505 TI - Hypotension associated with spinal anaesthesia for caesarean section. PMID- 8211506 TI - The growth of South African black children. PMID- 8211507 TI - Micronutrients and cholesterol. PMID- 8211508 TI - A modified caulking gun for contrast injection. PMID- 8211509 TI - Sensitisation, pre-emptive and total analgesia. PMID- 8211510 TI - The resurrection of primary percutaneous transluminal coronary angioplasty for the treatment of acute myocardial infarction. PMID- 8211511 TI - Primary health care depends on the district health system. PMID- 8211512 TI - Comprehensive PHC services rendered by local authorities--the experience of the Department of Health Services and Welfare, House of Representatives. PMID- 8211513 TI - The role of non-government organisations in the district health system. PMID- 8211514 TI - Managing primary health care in South Africa at district level--the MRC/IUPHC Workshop. PMID- 8211515 TI - Developing district health systems in the rural Transvaal. Issues arising from the Tintswalo/Bushbuckridge experience. AB - District health systems are increasingly acknowledged as a foundation for national health services based on primary health care. Initial efforts to institute a demonstration district health system in the Bushbuckridge area of the eastern Transvaal are described. These include efforts to overcome the organisational and administrative fragmentation caused by homeland and provincial boundaries. Close attention needs to be given to district-level health management, the complementary roles of district and regional health authorities, working relationships and accountability among professional staff from different disciplines, involvement of the community in a district health authority and the district health system as an element of local government. PMID- 8211516 TI - A district health service in Khayelitsha--panacea or pipedream? AB - Khayelitsha is an underserviced, largely informal urban settlement on the edge of Cape Town. It is home to some 350,000 people. This paper maintains that a district health service would be beneficial in Khayelitsha. Advantages include (i) the integration and co-ordination of services with coherent management of health care; (ii) the ability to prioritise and act on problems with the full range of preventive and curative measures as well as intersectoral support; and (iii) the accountability of health providers. Some of the steps taken towards the initiation of a district health service are illustrated in a discussion of the recent changes in health service structures in Khayelitsha. There are many obstacles to the implementation of a formal district health service and these are discussed briefly. PMID- 8211517 TI - Utilisation of public health services by caregivers of children from Khayelitsha presenting with acute diarrhoea. AB - Patterns of public sector health service utilisation in relation to severity and weekday or weekend occurrence were identified for children from Khayelitsha with diarrhoeal disease. The current organisation of local services is inappropriate for the provision of basic primary care for these children. Given the inadequate access to appropriate care, caregivers select their health service options rationally. This paper recommends that a 24-hour rehydration unit be established in Khayelitsha to improve the effectiveness and appropriateness of the management of these children. PMID- 8211518 TI - Far fewer missed opportunities for immunisation in an integrated child health service. AB - The mobile nature of the population of Khayelitsha makes it imperative that opportunities for immunisation of children are exploited at every visit to health services. Previous studies have demonstrated a high incidence of missed opportunities for immunisation at curative health services. The occurrence of undetected opportunities for immunisation are compared at two primary care institutions: one in which curative and preventive services are provided separately, and one in which these functions are integrated. Far fewer opportunities for immunisation were missed at the integrated service, underscoring the urgency of integrating child health services throughout the country. PMID- 8211519 TI - Missed opportunities for immunisation in Natal health facilities. AB - The World Health Organisation currently recommends that preventive measures be promoted at every contact with health services. However, there is still no uniform policy on immunisation currently implemented at curative health facilities in Natal. Surveys of missed opportunities for immunisations in four health facilities in Natal revealed that, even in those with an immunisation policy, many opportunities are still being missed. The reasons for this included a lack of emphasis on preventive measures by health workers, reluctance to open vaccines for only a few children, and vaccines not being immediately to hand. It is recommended that a firm policy be implemented in Natal, with regular self evaluation by the health facilities. PMID- 8211520 TI - Breast-feeding and weaning practices in Venda, 1990. AB - A stratified random cluster survey, using a structured interview schedule, was performed to determine the prevalence, frequency and duration of breast-feeding among Venda mothers as well as the foods that Venda children commonly ate in their first 2 years of life. Nearly all children under 2 years old were being breast-fed and virtually all of these were fed on demand. Approximately 60% of infants under 3 months of age and virtually all others under 2 years old received supplementary foods daily. A further 30% of infants under the age of 3 months were given supplementary water daily. Forty per cent of infants under 3 months old and virtually all in the other age groups were given carbohydrates daily. Protein foods, vitamin/mineral and high-energy sources were given less frequently. Only 12% in the 6-11-month age group and 21% in the 12-23-month age group received a balanced diet daily. A significant proportion of children in all age groups received only carbohydrates over and above breast-milk. Traditional mixes were infrequently given. More research is needed to assess actual breast milk production by mothers whose children are being fed supplementary foods. The effect of socio-economic status on weaning practices and that of weaning practices on nutritional status need to be investigated. Food supplementation and nutrition education programmes need to be intensified. PMID- 8211521 TI - Expectant management of early onset of severe pre-eclampsia in Durban. AB - Fifty patients with severe pre-eclampsia who presented before 32 weeks' gestation were managed conservatively (sedation, bed rest, antihypertensive therapy and intensive fetal and maternal monitoring) until intervention was indicated. Twelve patients presented before 26 weeks of pregnancy and there were no fetal survivors in this group; 23 presented between 26 and 29 weeks and 8(34,8%) of the babies in this group survived. The rate of perinatal loss in those presenting between 30 and 32 weeks was 26,6% (N = 4). Patients who had a history of a hypertensive disorder in their previous pregnancy(ies) had a higher perinatal mortality rate; 23 such mothers experienced 16 perinatal losses compared with 27 mothers who had no such history and who had only 8 perinatal losses. There was 1 maternal death, there were 2 cases of eclampsia, 3 of pulmonary oedema, 4 of abruptio placentae and 1 case of renal failure; 2 patients had disseminated intravascular coagulation. The local indigent and underprivileged black population have a more aggressive form of early onset of severe pre-eclampsia than that reported for other population groups. The high maternal complication rate of 30,8% and the low fetal survival rate before 26 weeks indicate that there is no place in our setting for expectant management of severe pre-eclampsia in patients presenting before 26 weeks. This applies particularly to those with a previous history of hypertension in pregnancy. PMID- 8211522 TI - Protein-losing enteropathy in Transkeian children with morbid protein-energy malnutrition. AB - A commercially available radial immunodiffusion assay was used to measure serum and faecal alpha 1-antitrypsin concentrations as well as alpha 1-antitrypsin clearance in 17 children with kwashiorkor, 11 children with marasmic kwashiorkor, 10 children with marasmus, and 16 normal children. Serum alpha 1-antitrypsin concentrations were significantly higher than normal in the marasmus and marasmic kwashiorkor groups, and significantly lower than normal in the kwashiorkor group. The intestinal clearance of alpha 1-antitrypsin was significantly higher than normal in the marasmus and marasmic kwashiorkor groups, and significantly lower than normal in the kwashiorkor group. There was a significant inverse correlation between the alpha 1-antitrypsin clearance and serum albumin concentration in the marasmus and marasmic kwashiorkor groups. No such correlation was evident in the kwashiorkor group. It is concluded that protein-losing enteropathy is likely to play a significant role in the development and perpetuation of hypo-albuminaemia in children with marasmus and marasmic kwashiorkor but not in those with kwashiorkor. PMID- 8211523 TI - Prevalence and causes of low vision and blindness in northern KwaZulu. AB - A survey of the prevalence of blindness and low vision was conducted in the Ingwavuma district of KwaZulu to assess the effectiveness of existing eye care facilities in the prevention and treatment of impaired vision and blindness. One hundred subjects from each of 60 randomly selected clusters (N = 6,090) were screened. Of these, 293 were identified and referred to an ophthalmologist for examination. Of the 268 (91,5%) examined, 241 were found to have visual impairment. Sixty-one of these people were blind, 85 had low vision, 61 were blind in one eye but had normal vision in the other, and 34 had low vision in one eye but normal vision in the other. The prevalence of blindness was 1,0% (95% confidence interval 0,7-1,2%), and the prevalence of impaired vision was 1,4% (95% confidence interval 1,1-1,7%). Age-related cataract (59,0%) and chronic glaucoma (22,9%) were the two main causes of blindness. Age-related cataract (75,3%), refractive error (10,0%) and chronic glaucoma (4,7%) were the main causes of impaired vision. Existing eye care services for the region have reduced the prevalence of blindness by only 7,0%. The training of ophthalmic nurses and the establishment of a sight-saver clinic in the area are necessary to reduce the prevalence of low vision and blindness. PMID- 8211524 TI - Presenting features of primary angle-closure glaucoma in patients of mixed ethnic background. AB - The relative frequency with which patients++ present with acute or chronic angle closure glaucoma depends on their ethnic background. In order to examine the presenting features and effects of primary angle-closure glaucoma in people of mixed ethnicity, we reviewed all 'coloured' patients who presented to Groote Schuur Hospital with this diagnosis during a 5-year period. Of the 92 patients, 33 (36%) presented with acute angle-closure glaucoma and 59 (64%) with chronic angle-closure glaucoma. The level of intra-ocular pressure on presentation correlated well with the number of quadrants of angle closure (correlation coefficient: r = 0.73, P < 0.001). When individual eyes were assessed, a mean cup/disc ratio of > or = 0.8 was present in 35% (65/184) and glaucomatous visual field loss was present in 56.5% (104/184). Total uni-ocular blindness secondary to chronic angle-closure glaucoma, was found in 16 (17%) patients. This study indicates that 'coloured' patients with primary angle-closure glaucoma are more likely to present with chronic symptoms and signs, and that the disease may result in devastating ocular damage and visual loss. In patients of mixed ethnic background with signs of primary glaucoma, chronic angle-closure should be excluded by careful gonioscopic evaluation of the drainage structures of the eye. PMID- 8211525 TI - The reliability of mortality data in Johannesburg. AB - Information on deaths in Johannesburg is collected on a voluntary basis by the Johannesburg City Health Department from the Department of Home Affairs regional offices as well as state mortuaries in the area. The reliability of these routinely collected data was assessed. Records of deaths of Asians, coloureds and whites from 1 July 1989 to 31 December 1989 were included in the study. Burial orders obtained from the different cemeteries and crematoria in the area were compared with the routinely collected mortality data. Two thousand eight hundred and thirty-seven deaths were included in the study. One hundred and ninety (6%) deaths in the department's records could not be found among the corresponding burial orders while 1,019 (36%) burial order records were not found among the department's routinely collected mortality data. Underreporting of deaths was greatest among the aged (43%) and infants (39%). When this underreporting was taken into account, the corrected infant mortality rate was 19.1/1,000 live births as opposed to 14.1. Recommendations are made for the improvement of the quality of routinely collected mortality data. PMID- 8211526 TI - Changes in total death rate and in ischaemic heart disease death rate in interethnic South African populations, 1978-1989. AB - Ischaemic heart disease (IHD) in prosperous Western populations rose markedly in the 1940s, peaked between 1970 and 1975 and then fell variably--by about 50% in the USA and Australia. Undoubtedly, decreases in serum cholesterol levels, in the incidence of hypertension and in smoking frequencies are largely responsible. In South Africa, in all population groups other than blacks, IHD rates rose analogously, with Asians and whites attaining very high rates. However, from 1978 to 1989, the total death rate among white males (per 100,000 world population) fell from 1,002 to 631 (37%), and the IHD mortality rate from 312 to 139 (56%). Rates for Asians were 1,306-1,130 (14%) and 355-226 (36%), respectively, and for coloureds 1,691 to 1,392 (18%) and 171 to 110 (36%). For blacks, the total mortality rate remained unchanged; IHD rates were low, but these data are unreliable. Percentage falls in the IHD rate exceed those in the total death rate, especially among whites, indicating true decreases in IHD rate. Understandably, the accuracy of the data, as with such data overseas, is questionable. Local falls are none the less in line with those noted in Western countries. Rates for whites remain very high, and are even higher for Asians. While knowledge of the reasons for the rises and falls in IHD rates remains incomplete, whites have none the less taken some preventive action, although Asians and coloureds apparently little. PMID- 8211527 TI - Primary care in South Africa. Reflections on conceptualisation and a review of the recent literature. AB - This paper reviews the various interpretations and connotations of the term 'primary care' as employed in South African literature and practice. There is a need for clear definitions of key concepts and the utility of the primary care framework proposed by Barbara Starfield is suggested in this regard. The paper also reviews and evaluates the research on primary care in South Africa published since 1988. PMID- 8211528 TI - Scheduling of occupational asthma as a compensable disease. PMID- 8211529 TI - Malaria chemoprophylaxis. PMID- 8211530 TI - Safety of non-steroidal anti-inflammatories before adenotonsillectomy. PMID- 8211531 TI - Reversal of acute resistant asthma by beclomethasone. PMID- 8211532 TI - Isolated angiitis of the central nervous system. PMID- 8211533 TI - Contact tracing and the estimation of sexual mixing patterns: the epidemiology of gonococcal infections. AB - BACKGROUND AND OBJECTIVES: The concept of a core group of individuals who change sexual partners frequently has played an important role in the study of the epidemiology of sexually transmitted diseases (STDs). It is widely believed that the core group is important in the persistence of infection and that it provides a sensible target for control interventions. GOAL OF THIS STUDY AND STUDY DESIGN: Simple mathematical models are used to assess the significance of sexual mixing between core and noncore groups. Published data from contact tracing studies, which base the definition of the core group on gonorrhea incidence by area of residence, are used to derive estimates of the degree of mixing within and between groups. RESULTS: Analyses reveal patterns of high mixing within core groups in the urban study sites, which suggests that within-group transmission ensures the persistence of gonococcal infection in the community as a whole. CONCLUSIONS: An extension of the analysis of contact tracing data to facilitate the development of mathematical models of STD transmission is detailed. PMID- 8211534 TI - Artificial nodules of the penis. Report of six cases among Russian immigrants in Israel. AB - BACKGROUND: Artificial penile nodules are foreign bodies implanted under the skin of the penis to enhance sexual pleasure. It is frequently encountered in Asian countries, but rarely in western countries. Most of the subjects are soldiers, drug addicts, sailors, prisoners, or members of low economic groups. GOAL OF THE STUDY: Our experience and review of the literature are reported. STUDY DESIGN: During a circumcision program among Russian adult immigrants in Israel, such plastic nodules were encountered. RESULTS: The nodules were found in six men, for a prevalence of 0.64%. CONCLUSION: Physicians should be familiar with this practice in certain groups of men, and especially Asian men. This report suggests that it may be widespread elsewhere in the world. PMID- 8211535 TI - Evaluation of the rapid plasma reagin "teardrop" card test for screening of syphilis in field conditions. AB - BACKGROUND AND OBJECTIVES: The availability of simple diagnostic methods may contribute to more efficient control of sexually transmitted diseases (STDs) in developing countries. For the detection of syphilis, a simple rapid plasma reagin (RPR) "teardrop" assay for finger-prick blood samples was developed in 1962. The reliability of this test is compared with RPR, Treponema pallidum hemagglutination assay (TPHA), and fluorescent treponemal antibody absorption (FTA-Abs) assays performed on venous blood samples. GOAL OF THIS STUDY: To evaluate the potential usefulness of the finger-stick RPR teardrop assay for diagnosis of syphilis in settings with poor medical resources. STUDY DESIGN: Pregnant women evaluated at two health centers in Pikine, Senegal were tested for STDs. The RPR teardrop assay was performed on plasma from blood samples obtained by finger prick, and standard RPR, TPHA, and FTA-Abs procedures were performed on serum obtained by vein puncture. RESULTS: The sensitivity and specificity of the finger-prick RPR teardrop assay were 69.7% and 96.5%, respectively, and its reactivity was correlated with RPR serum antibody titer. CONCLUSION: The finger prick RPR teardrop assay is not a reliable alternative to the classic serum RPR test. PMID- 8211536 TI - Prevalence of isolated urethral asymptomatic Chlamydia trachomatis infection in the absence of cervical infection in incarcerated adolescent girls. AB - BACKGROUND AND OBJECTIVES: Adolescent girls may have isolated asymptomatic urethral Chlamydia trachomatis infection. GOAL OF THIS STUDY: To determine if a single direct fluorescent antibody (DFA) slide can detect as many urethral and cervical infections as the use of separate slides and to determine if isolated urethral infection occurs. STUDY DESIGN: During pelvic examinations upon admission, DFA slides were prepared from the cervix, from the urethra, and with cells from both sites. RESULTS: Of 125 girls, 17 had C. trachomatis infection: 4 in the urethra only (24%), 5 in the cervical sample only (31%), 5 in both sites (31%), 3 had positive results only on the combined slide, and 1 had a positive result on the cervical slide and an inadequate urethral slide. CONCLUSION: Isolated urethral C. trachomatis infection occurs frequently, and sampling both sites as opposed to sampling the cervix alone increases the number of cases found by 24% (P < 0.002). Using a single slide to detect infection in both sites detects as many infections as using two separate slides. PMID- 8211538 TI - Mortality patterns among persons with antecedent syphilis infection. AB - BACKGROUND AND OBJECTIVES: Few studies have examined the patterns of death among persons with a history of syphilis infection. GOALS OF THIS STUDY: This analysis examines the cause-specific mortality patterns among a cohort of persons diagnosed with syphilis. STUDY DESIGN: Individuals diagnosed with serologically confirmed syphilis in New York State (excluding New York City) between 1972 and 1987 were matched to the New York State mortality files to identify the deaths among members of the cohort. RESULTS: The overall observed mortality between 1973 and 1987 was generally comparable to the expected number among both men (SMR = 0.94; 95% CI = 0.87-1.02) and women (SMR = 0.88; 0.78-0.99). An excess of deaths due to all causes was observed among men between the ages of 25 and 54 (SMR = 1.74; 1.53-1.97), with the largest excess observed in the 25- to 34-year-old age group (SMR = 2.32; 1.87-2.85). Among men, excesses were noted for deaths due to AIDS-related causes. Among both genders, excess deaths were observed for possible alcohol-related causes. CONCLUSION: The unique mortality patterns of this cohort suggest the need for increased identification of and interventions directed toward high-risk behavior of individuals diagnosed with syphilis. PMID- 8211537 TI - Patterns of condom use and sexual behavior among never-married women. AB - BACKGROUND AND OBJECTIVES: Use of condoms is one of the main methods sexually active persons may choose to prevent infection with sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV). Little is known about patterns of condom use among women in the United States. We provide a conceptualization of patterns of condom use and factors associated with these patterns. GOAL OF THIS STUDY: To examine patterns of condom use and associated characteristics among sexually active, never-married women in the United States. STUDY DESIGN: Analysis of data from the 1988 National Survey of Family Growth, which is a nationally representative sample of women in their childbearing years. RESULTS: Only a minority of sexually active, never-married women report using condoms, and even fewer report using them consistently. Women with characteristics traditionally associated with increased risk of infection with STD and HIV appear to be less likely to report using condoms and to report using them consistently. Women who report use of condoms to prevent STDs are more likely to report consistent condom use; less likely to cease using condoms; and more likely to initiate consistent condom use. CONCLUSION: Findings suggest the need for innovative programming targeted for specific sexually active populations to promote both initiation and maintenance of use of condoms. PMID- 8211539 TI - The role of spermatozoa in the pathogenesis of Chlamydia trachomatis salpingitis in a primate model. AB - BACKGROUND AND OBJECTIVES: The role of spermatozoa in carrying microorganisms from the cervix to the fallopian tubes and promoting infection was examined in eight pig-tailed macaques. GOAL OF THIS STUDY: The aim of this study was to determine whether spermatozoa play a role in the transport of Chlamydia trachomatis into the upper reproductive tract and in the pathogenesis of chlamydial salpingitis. STUDY DESIGN: Five monkeys were inoculated with Chlamydia trachomatis in the cervix and mated, and three other monkeys were infected in the cervix but not mated. RESULTS: Culture positive results were obtained for cervical samples from all animals. After cervical inoculation, no mated animals and one unmated animal had positive culture results for samples from the fallopian tubes. After mating, no spermatozoa examined in samples taken from the upper tract or cul de sac had elementary bodies (EBs) on their surfaces, and only one sample obtained from the cervix showed C. trachomatis attached to the spermatozoa, as determined by fluorescent antibody (FA) staining. Two of the mated monkeys became pregnant; one spontaneously aborted late in gestation, and the other delivered a normal female infant. The fallopian tubes of all eight monkeys were challenged directly with serovar D and examined for evidence of salpingitis. Repeat laparoscopy was performed to monitor the inflammatory response. Tubal specimens for isolation and polymerase chain reaction (PCR) were obtained. Hysterectomies were performed between 3 and 4 weeks after tubal inoculation. Histopathologic examination of the fallopian tubes revealed widespread inflammation consisting of focal collections of lymphocytes and plasma cells in the submucosa. Peritubal adhesions were observed in four of five mated monkeys and in two of three unmated monkeys. CONCLUSION: This study failed to confirm that spermatozoa play a role in the pathogenesis of C. trachomatis infection. PMID- 8211540 TI - Comparison of enoxacin and ceftriaxone in the treatment of uncomplicated gonorrhea. AB - BACKGROUND AND OBJECTIVES: The increasing prevalence of resistant strains of Neisseria gonorrhoeae has prompted investigation of new agents for the treatment of this sexually transmitted disease. GOAL OF THIS STUDY: This study compared the efficacy and safety of a single oral dose of enoxacin to intramuscular ceftriaxone in the treatment of uncomplicated anogenital infection with N. gonorrhoeae. STUDY DESIGN: A randomized open trial was conducted at a sexually transmitted diseases clinic in Brooklyn, New York. Adults with uncomplicated gonorrhea were randomly assigned to receive 400 mg of enoxacin or 250 mg of ceftriaxone. A follow-up examination was conducted 5 to 9 days later. RESULTS: 59 women and 23 men were enrolled; 40 women and 19 men were evaluable. Enoxacin eradicated 18 of 19 endocervical, 10 of 10 urethral, 5 of 5 anorectal, and 3 of 3 pharyngeal gonococcal infections. Ceftriaxone eradicated 20 of 21 pharyngeal gonococcal infections. Fifty-nine pretreatment isolates of N. gonorrhoeae were available for antimicrobial susceptibility testing. The geometric mean minimal inhibitory concentration was 0.03 mg/1 for enoxacin and 0.005 mg/l for ceftriaxone. There were few sides effects in either group, and both drugs were ineffective against concomitant infection with Chlamydia trachomatis. CONCLUSION: Oral enoxacin appears to be a safe and effective method of treatment for anogenital infections caused by N. gonorrhoeae. PMID- 8211541 TI - Underestimation of HSV-2 seroprevalence in a high-risk population by microneutralization assay. AB - BACKGROUND: Complement independent neutralizing antibody assays (CINA) have been used in seroepidemiologic studies and in diagnostic laboratories to distinguish between antibodies to herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). The accuracy of CINA has not been rigorously tested against protein-specific typing assays, such as Western blot. GOAL OF THIS STUDY: To determine the ability of CINA to identify HSV-2 antibodies alone or in the presence of HSV-1 antibodies. STUDY DESIGN: Sera from randomly selected women at the Seattle King County Sexually Transmitted Disease Clinic were tested by CINA and Western blot. RESULTS: Of 521 women tested, 81% had HSV antibodies by Western blot and 76% had neutralizing antibodies. Of 220 sera with HSV-2 antibodies by Western blot, 106 (48%) were serotyped correctly by CINA. Of the women studied, 140 (27%) had type indeterminate neutralizing antibodies; 55 of these sera (39%) had antibody only to HSV-1 by Western blot. CONCLUSION: The seroprevalence of HSV-2 in an STD clinic population was seriously underestimated by CINA. PMID- 8211542 TI - Syphilis prevalence among unregistered prostitutes in Istanbul, Turkey. PMID- 8211543 TI - Treatment of gonorrhea with ampicillin/sulbactam. PMID- 8211544 TI - [Infectious diseases and blood transfusion]. PMID- 8211545 TI - [Transmission cytomegalovirus infection by blood transfusions]. PMID- 8211546 TI - [Autotransfusion and pregnancy]. AB - PURPOSE: To analyse the results of a pre-deposit autologous transfusion programme in pregnant women on their third period of pregnancy. MATERIAL AND METHODS: Fifty donor/pregnant women were included in the study. They were in the third trimester of their pregnancy and had risk of requiring transfusion during or after surgery. Haemoglobin above 11 g/dL and haematocrit above 34% were required in each case. Phlebotomy was performed at one-week intervals, iron and folate being supplied. Constants such as foetal heart frequency were evaluated, the programme being interrupted in case of foetal bradycardia. Apart from weight, Apgar and Silverman scores were applied to each newborn. RESULTS: Cephalopelvic disproportion was the commonest obstetric indication, 26 cases (52%). For autologous blood transfusion, rare blood groups, 12 cases (24%), followed by intra- or post-operative bleeding risk, 10 cases (20%) and being Jehovah's Witnesses, 9 cases (18%), were the major indications. Ninety-four blood units were drawn, 34 of them being used. The remaining 60 units were used for homologous transfusion. No complications developed during phlebotomy and the neonatal determinations showed no significant anomalies. CONCLUSIONS: (1) Autologous blood transfusion with pre-deposit in the third trimester of pregnancy is a safe and effective way of collecting blood. (2) Its indication is not reduced to rare blood groups. (3) The procedure seems to be safe for both the mother and the newborn. PMID- 8211547 TI - [Changes in the hemogram and in the laboratory parameters indicative of iron metabolism in mild viral infections]. AB - PURPOSE: To assess the duration and intensity of the changes appearing in laboratory values related to iron utilisation during viral infection. MATERIAL AND METHODS: With previous parental consent, 120 eutrophic infants received vaccination with attenuated measles virus or a combination of measles, mumps and rubella viruses as a model of mild viral infection. A number of laboratory tests were performed on day 0 and in two later occasions (4-21, 9-14 or 9-30); these included blood cell counts, ESR, serum iron, total iron binding capacity, transferrin saturation index, free erythrocytic protoporphyrin, serum ferritin, intra-erythrocytic ferritin, direct anti-human globulin test and C-reactive protein. The statistical analyses were done in accordance with ANOVA, Student's t test, Wilcoxon, Kruskall - Wallis, Mann-Whitney and Fisher methods. RESULTS: A significant haemoglobin drop was seen on days 9 and 14 post-vaccination. This descent was > 10 g/L in 8.2% of the cases, and > or = 6 g/L in 19.6%. Serum iron and transferrin saturation decreased significantly, whereas mean corpuscular volume, free erythrocyte protoporphyrin and serum ferritin were significantly increased. All these but protoporphyrin recovered by day 30. Subjects with normal iron metabolism figures on day 0 and those whose thermal variations were above 38 degrees C had greater changes in the figures related to iron metabolism. CONCLUSION: The evaluation of iron metabolism is not reliable if the patient has suffered from infection, although a mild viral one, in the three weeks prior to the study. PMID- 8211548 TI - [The adaptation of human bone marrow adipose tissue to various degrees of hematopoietic cellularity]. AB - PURPOSE: To assess whether the variations in the number and size of the adipocytes are proportional, or not, to the changes of the fat tissue fraction (FF) associated to different degrees of hematopoietic cellularity of the bone marrow. MATERIAL AND METHODS: The material was made up of 28 specimens of bone marrow biopsy, from which 265 microscopic fields representing a wide range of FF were obtained. As index of proportionality, the ratio N/S (adipocyte number/size) was employed. RESULTS: The parameters FF and N/S showed a highly significant correlation (r = 0.89; p = 0.00000003) at low-normal FF range (< 40%), whereas at high FF range (> 40%), such a correlation was lacking (r = 0.01; p = 0.86). CONCLUSION: At low-normal FF the adipocyte number and size vary proportionally. Conversely, at high FF, in some cases a more marked increase of number and in other instances of adipocyte size is detected. Further investigations are needed to find out the responsible factors for this different behaviour. PMID- 8211549 TI - [Hemostatic changes in extracorporeal surgery: pathogenesis and treatment]. PMID- 8211550 TI - [Platelet function after allogeneic bone marrow transplantation in Wiskott Aldrich syndrome]. AB - PURPOSE: To assess the platelet characteristics and functionalism in the Wiskott Aldrich syndrome (WAS) after allogeneic BMT using cyclophosphamide and busulphan for conditioning. MATERIAL AND METHODS: Two WAS patients underwent allogeneic BMT. Platelet aggregation was studied prior to and after BMT, along with the intraplatelet amount of ADP and ATP. RESULTS: Platelet count, size and aggregation wholly recovered after BMT. The post-transplant content of platelet nucleotides was normal. CONCLUSIONS: Platelet function can be totally restored with cyclophosphamide/busulphan conditioned BMT in WAS. Platelet defects in this disease are due to defective thrombopoiesis. PMID- 8211551 TI - [Alloimmune neonatal neutropenia: flow cytometry study of the 1st patient described in Spain with identification of an anti-NA1]. AB - A strong antibody was found in a mother (first pregnancy) who had a severe neutropenic baby. The father's granulocytes were typed by flow cytometry as NA1+, NA2+, NB1+, ND1+ and the mother as NA1-, NA2+, NB1+ and ND1+. The antibody was identified as anti-NA1 by us, and confirmed later by a reference laboratory. The serum reacted with 54.8% of the 31 donors tested. The same antibody was found in the child's serum 35 days after birth, and the reactivity was stronger than in the mother's serum. The HLA-DR, DQ from the mother was DR3, DR7; DR52, DR53; DQ2. The baby's granulocytes were recovered slowly over a four-month period, but the course was benign without any specific treatment. Five months after birth, with recovery, the child's serum became negative and his granulocytes were confirmed as NA1+. Due to the difficulties in fully diagnosing and working with granulocytes we suspect that there are undetected cases; only one case has been recorded in Spain before. PMID- 8211552 TI - [Safe minor surgery in patients taking anticoagulants]. AB - The effectiveness of a commercial drug containing fibrinogen, thrombin and factor XIL (Tissucol, Immuno) was assessed in 127 patients receiving oral anticoagulant treatment with acenocoumarin who were subjected to 183 minor surgical procedures: 107 exodontia, 53 periodontal procedures, 17 combinations of the former, 4 liver biopsies and 2 skin biopsies. All but the liver biopsies were performed in the outpatient clinic. Mild haemorrhage appeared in 21 instances. None of the patients required systemic administration of coagulation factors, and the maneuvers did not take any longer than in patients with integrity of the coagulation mechanisms. The outstanding benefits of this technique are: less discomfort for patients, who can be subjected to a single procedure while otherwise requiring several sessions; anticoagulation needs not be discontinued, subcutaneous heparin being otherwise necessary; low risk of complications and avoidance of substitutive therapy; lesser economic burden, as no hospital admission is needed. PMID- 8211553 TI - [Blood bank quality control guidelines]. PMID- 8211554 TI - [Pyoderma gangrenosum and Sweet's syndrome in a case of chronic myeloid leukemia]. PMID- 8211555 TI - [Sweet's syndrome and pyoderma gangrenosum in a patient with idiopathic myelofibrosis]. PMID- 8211556 TI - [Preleukemic visceromegalic myeloma]. PMID- 8211557 TI - [Combined therapy with mitoxantrone and cytosine arabinoside as a first-line treatment in ANLL: preliminary results]. PMID- 8211558 TI - [Unfavorable effect of splenectomy on a myelodysplastic syndrome with a prolonged course]. PMID- 8211559 TI - [The study of hemostasis in the emergency laboratory]. PMID- 8211560 TI - Beneficiaries affected by the annual earnings test, 1989. AB - The earnings test of the Social Security Act has, since its introduction in 1939, been one of the more controversial provisions of the Act. The controversy has centered on the role that the test plays on the retirement decision and the issue of whether or not Social Security benefits become an "earned right" after an individual reaches retirement age and therefore should be paid regardless of subsequent earnings. This article presents a history of the earnings test and how it has evolved into the test in effect today. It presents demographic data for the 1,241,000 beneficiaries who in 1989 had at least ! in benefits withheld as a result of the test. Of this total, 926,000 were retired-worker beneficiaries. The other persons affected by the test were dependents and survivors who had benefits offset due to their own earnings. Collectively, these persons had over % billion in benefits withheld. In addition to these persons, there is a potentially large group of individuals who never filed for benefits because they knew that their benefits would be withheld. PMID- 8211561 TI - The role of pensions in retirement income: trends and questions. AB - Pensions are an important and increasingly common supplement to Social Security benefits for persons aged 65 or older--particularly for those in the the middle and upper income quintiles. By 1990, pension income was reported by 44 percent of all elderly units--57 percent of the couples and 34 percent of unmarried persons. This article discusses the role of pensions in the income of the elderly; private pension coverage, vesting, and types of plans among active workers; how the shift toward defined contribution plans poses new problems in assessing the role of private pensions in providing retirement income security; and expected pension receipt rates for the future elderly. Pension receipt among the elderly is expected to continue to grow over the next 20-30 years because of past growth in coverage and vesting. Microsimulation models are a relatively new tool for forecasting the future distribution of pension income. The models offer a framework for considering the research questions that, if answered, would help improve our understanding of the impact of the pension system on future income security. PMID- 8211563 TI - Shifting the cost of self-pay for SSI workers in supported employment. AB - Two provisions of the Supplemental Security Income (SSI) program--the Plan for Achieving Self-Support (PASS) and Impairment Related Work Expenses (IRWE)--can have the implicit result of compensating SSI recipients for work expenses they incur. That is, PASS and IRWE can, in effect, shift all or some of a working SSI recipient's expenses from the recipient to the SSI program. This article describes how PASS and IRWE operate and demonstrates the shifting effect. The analysis focuses on expenses for supported employment. PMID- 8211562 TI - Economic well-being of the old old: family unit income and household wealth. AB - This article examines the family income and the household wealth and income of old old persons. Subgroups of the old old are compared and the old old are compared with the young old. When the old old group is separated into three subgroups--widows living alone, other females, and males--the economic status of widows living alone is substantially below that of the other two subgroups. This difference is found when income, wealth, and combined income-wealth measures are used. When the old old group is compared with the young old group, the economic status of the old old is substantially lower for all measures examined. When the three subgroups within both the old old and young old groups are compared, the economic status of each subgroups is lower for the old old for most measures. Income data from the March 1991 Current Population Survey and wealth and income data from the 1984 Survey of Income and Program Participation are used. PMID- 8211564 TI - Actuarial status of the Social Security and Medicare programs. AB - The Boards of Trustees for the two Social Security and the two Medicare Trust Funds recently released their annual reports to Congress detailing the operations of the trust funds during 1992 and their projected financial status for future years. Based on the Trustees' best estimates, the reports show: The Federal Old Age and Survivors Insurance (OASI) Trust Fund is projected to be able to pay benefits for about 50 years. Congress will eventually need to take action to assure the long-range financial soundness of the program. The Federal Disability Insurance (DI) Trust Fund is projected to be exhausted in about 2 years. As a result, the Board urges that prompt legislative action be taken to improve the financial integrity of this trust fund by reallocating to the DI fund a larger share of the overall OASDI tax rate. The Federal Hospital Insurance (HI) Trust Fund is projected to be able to pay benefits for only about 6 years and is severely out of financial balance in the long-range. The Trustees urge the Congress to take additional actions designed to control HI program costs through specific program legislation and as a part of enacting comprehensive health care reform. The Federal Supplementary Medical Insurance (SMI) Trust Fund is financed on a year-by-year basis and is adequately financed. The Trustees urge the Congress to take additional actions designed to control SMI costs through specific program legislation and as a part of enacting comprehensive health care reform. PMID- 8211565 TI - Income security in transition for the aged and children in the Soviet Union and in the Russian Federation. AB - A dynamic process of social security reform took place during the economic transition in the Soviet Union from 1985 through 1991, and in the Russian Federation in 1992. Despite administrative and financial difficulties, the Gorbachev reform objectives have been incorporated (with modest revisions) into the Russian Federation pension legislation and family allowance programs. Following the adoption of a radical economic reform policy in January 1992, policymakers in the Russian Federation have been hard pressed to meet rising social needs under severe fiscal constraints. As the number of the vulnerable population has increased, and as the emerging poor have had to face more severe hardships, the social security system has overcome unprecedented political and economic disruptions to become fully operational. Local governments and civic groups are organizing assistance to help meet needs where the State-operated programs have been inadequate. These efforts, however, have been made haphazardly. PMID- 8211566 TI - Exploring the use of the public's views to set income poverty thresholds and adjust them over time. AB - This study considers how the views of the public at large may be used to define the poverty income level. The basic data for the study come from routine Gallup surveys conducted since the beginning of the post-World War II period that asked representative samples of adults in the United States to estimate the smallest amount of money that a family of four needs to "get along." Additional Gallup surveys undertaken in 1989 established the income corresponding to the poverty level using a similar approach. The author constructs a set of poverty thresholds, covering the post-World War II period, based on the single point-in time poverty/get-along income relationship in 1989 and the full get-along series. Comparison of this set of thresholds with an alternative poverty series that is consistent with the Federal Government's official poverty measure yields three principal findings: (1) a poverty level consistent with the official measure was a good deal higher than the Gallup-based poverty threshold in the immediate post World War II period, (2) the income level of the official measure was likely consistent with the public's views about the poverty level at the time when the official measure was introduced, and (3) since the late 1960's and the early 1970's, the income level of the official measure has fallen increasingly below the Gallup-based poverty threshold until 1989 when the official measure was 20 percent below the Gallup series. It is suggested that the two series have diverged over time because the views of the public about poverty level income have responded to increases in real income that have occurred since World War II while the official measure has remained fixed in real terms. PMID- 8211567 TI - Proposals to modify the taxation of Social Security benefits: options and distributional effects. AB - This article presents simulation estimates of the income-distributional effects in 1994 of several proposals to modify the taxation of Social Security benefits under the Federal personal income tax. Under the benefit-taxation provisions that have been in effect since 1984, up to 50 percent of benefits are included in taxable income for taxpayers with incomes above certain thresholds. In 1994 about 20 percent of beneficiary families will pay a larger income tax as a result of these provisions. Because of the benefit taxation thresholds, the affected families are concentrated in the upper half of the income distribution: about 70 percent of these families have incomes that put them in the top 30 percent of families by income. If the current taxation thresholds were kept and the percentage of benefits includable in taxable income were raised above 50 percent, the tax effect would remain concentrated on the upper income families. If, on the other hand, the percentage includable were kept at 50 percent while the taxation thresholds were lowered or eliminated, more beneficiary families with incomes in the middle deciles would become affected. The lowest income beneficiary families, however, would remain unaffected, because their benefits would be protected from income taxation by exemptions and the standard deduction. The simulations indicate that only a very few families in the bottom 20 percent of families by income would be affected even if the benefit taxation thresholds were eliminated entirely. PMID- 8211568 TI - Social Security and older workers. AB - Many observers have noted that the long-term decline in labor-force participation by older Americans may reflect the evolution of social institutions that effectively discourage work. Often cited factors include employer discrimination against older workers, private pension plans that penalize continued employment, and the Social Security system. Various policies, such as eliminating Social Security's retirement test, have been proposed with a view to eliminating or lessening employment barriers. This article summarizes the economic evidence that addresses the role played by the Old-Age and Survivors Insurance (OASI) programs in retirement decisions. OASI is shown to have statistically significant effects on both the timing of retirement and the amount of postretirement work; however, the influence is not large relative to the many other factors that determine the labor-supply decisions of older workers. Consequently, changes in Social Security policy of the type and magnitude that are politically feasible are unlikely to result in large changes in retirement behavior. PMID- 8211569 TI - A comparison of the recovery termination rates of disabled-worker beneficiaries entitled in 1972 and 1985. AB - This article reports on the final phase of a longitudinal analysis of two cohorts of Disability Insurance (DI) beneficiaries. The analysis shows that changes in DI program provisions and demographic shifts in the beneficiary population have considerably affected standard recovery termination rates. Several covariates were also found to affect the rates, particularly age and education. Overall, the 1985 cohort has a lower standard recovery termination tendency during the first few years of entitlement. After an attempt was made to define a recovery event for the 1985 cohort to make it comparable to the 1972 cohort, it was found that the termination rate for the 1985 cohort was still lower than the termination rate for the 1972 cohort. These findings suggest that there will be fewer recoveries for beneficiaries who entered the DI program in the late 1980's than for those who came on the rolls earlier. PMID- 8211570 TI - Social Security Bulletin. Annual statistical supplement, 1993. PMID- 8211572 TI - [Angiology 1993. 23rd Annual meeting of the Austrian Angiology Association. Feldkirch, 3-5 June 1993. Abstracts]. PMID- 8211573 TI - [Angiology 1993. 9th Joint annual meeting of the German, Austrian, and Swiss Associations for Angiology. Zurich, 24-27 August 1993. Abstracts]. PMID- 8211574 TI - Carcinoma of the anus treated with primary radiation therapy and chemotherapy. AB - Between 1983 to 1989, 24 patients with previously untreated carcinoma of the anal canal (less than 3 centimeters in five patients and more than 3 centimeters in 19 patients) were entered in a prospective nonrandomized protocol of primary radiotherapy (4,050-4,500 cGy days one to 28) and chemotherapy (10 milligrams per meter squared of mitomycin C, on day two and 1,000 milligrams of 5-fluorouracil per molar squared for days two to five and 28 to 32). Therapy was discontinued for two patients because of severe (grade 4) skin reactions. The remaining patients tolerated the regimen well, with the exception of two patients who had grade 3 hematologic toxicity and three patients with grade 3 to 4 complications of the gastrointestinal tract. All of the patients who completed the regimen had a complete clinical and pathologic response when restaged six weeks after completion of therapy. All patients with lesions of less than 3 centimeters and 13 of 19 patients with lesions greater than 3 centimeters have remained free of disease (median follow-up period of 41 months; median survival rate of 36 months). Before 1983, 19 patients underwent abdominal perineal resection as primary treatment for carcinoma of the anus. Only six of seven patients with lesions less than 3 centimeters and zero of the 12 patients with lesions equal or greater than 3 centimeters have remained alive and free of disease. Eighteen of 24 patients treated with chemotherapy and radiotherapy only have remained free of disease and have preserved anal function. These results are superior to those reported with primary surgical treatment and primary radiotherapy only. PMID- 8211576 TI - Blood lost and blood transfused in coronary artery bypass graft operation as implications for blood transfusion and blood conservation strategies. AB - We have analyzed the relationship between blood lost and blood transfusions given to 498 consecutive patients undergoing primary elective coronary artery bypass graft operations at 18 institutions. Seventy-nine percent of blood and 59 percent of patients were transfused only on the day of the operation. Patients who received none, 1 or 2 units of blood were not different when analyzed for blood transfusion risk factors except for the percentage of patients who were female. We identified 91 patients who received transfusion inappropriately, using a clinical indicator that analyzed blood losses for each patient. Forty-nine percent of all patients transfused could have avoided exposure to homologous blood if the equivalent of 4 units of the blood in erythrocyte volume had been provided for blood transfusion needs; if blood determined to have been transfused inappropriately had not been given, 95 percent of all patients would have received four or fewer erythrocyte units. We conclude that physician education and quality assurance programs need to be coupled with innovative blood conservation efforts that provide the equivalent of 4 units of homologous blood to minimize blood transfusions in this setting. PMID- 8211575 TI - Efficacy of hepatic transplantation in patients with primary sclerosing cholangitis. AB - Controlled trials to assess the therapeutic benefit of orthotopic hepatic transplantation (OHTx) for primary sclerosing cholangitis (PSC) cannot be justified in view of improvement of patient survival after this operation since 1981. However, the actual patient survival with OHTx can be compared with the Mayo model estimated survival probabilities without OHTx. This model, which encompasses physical, biochemical and histopathologic parameters of PSC, was constructed from a study of 392 conservatively treated PSC patients at five international centers in England and North America. We compared the actual survival of 216 adult patients with the diagnosis of advanced PSC who underwent hepatic replacement with the expected survival estimated by the Mayo PSC natural history model, "the simulated control technique." OHTx was performed at the University of Pittsburgh and Mayo Medical Center between 5 December 1981 and 26 December 1990. The mean (plus or minus standard deviation) post-OHTx follow-up period was 34 +/- 25 months (range of zero to 104 months). Before transplantation, biliary or portal hypertensive operation, or both, was performed upon 104 patients. At operation, the mean age of recipients was 42.1 +/- 11.3 years and the mean value of total serum bilirubin was 13.3 +/- 13.0 milligrams per deciliter. Extensive septal fibrosis and cirrhosis were histologically documented in 97 percent of the patients, with splenomegaly in 63 percent. Immunosuppressive therapy was based primarily on cyclosporin in 184 recipients and FK-506 in 32. Within six months, the Kaplan-Meier survival probability after OHTx (0.89) already was higher than predicted by the Mayo model (0.83). At five years, the Kaplan-Meier actual survival with OHTx was 0.73 compared with 0.28 expected Mayo model survival. The overall increased survival rate with transplantation was statistically significant (chi-square equals 126.6; p < 0.001). At all risk stratifications, OHTx significantly improved survival with a p value of 0.031 (low risk), 0.001 (moderate risk) and < 0.001 (high risk). Thus, OHTx is effective therapy for PSC. Disease gravity and unsuspected cholangiocarcinoma in the excised native liver adversely influenced short and long term survival rates after transplantation, respectively. PMID- 8211577 TI - Influence of mastectomy techniques on estrogen and progesterone receptor analysis in carcinoma of the breast. AB - Gradual tumor tissue devascularization during mastectomy is thought to decrease estrogen (ER) and progesterone (PgR) receptor activity. To determine whether or not hormone receptor values could be influenced by different mastectomy techniques, 62 patients with carcinoma of the breast had a Tru-cut needle (Baxter Healthcare Corporation) biopsy (premastectomy sample) and underwent modified radical mastectomy (postmastectomy sample) either before (group 1, 40 patients) or after (group 2, 22 patients) axillary lymph node dissection. When the two surgical procedures were compared in 33 patients in whom it could be assessed, no significant tendency (p = 0.51 for ER and p = 0.36 for PgR) for the postmastectomy sample to have hormone receptors levels less than samples taken at biopsy was detected. Overall, in the two groups (44 assessable patients), comparison with respect of each patient, between premastectomy and postmastectomy samples showed that the variations in either ER or PgR receptor values, determined by immunoenzymatic assays, were not statistically significant (p = 0.32 for ER and p = 0.21 for PgR). The current results indicated the relative stability of steroid receptors during the two modified radical mastectomy procedures and suggested that a systematic reference determination of hormone receptors on biopsy before modified radical mastectomy is unnecessary. PMID- 8211578 TI - Comparison of morbidity in cesarean section hysterectomy versus cesarean section tubal ligation. AB - This study was undertaken to compare the morbidity of cesarean section hysterectomy (C-HYST) and cesarean section bilateral tubal ligation (C-BTL) in a nonemergency or elective environment. Charts were reviewed for patients who underwent elective C-HYST or elective C-BTL before the onset of labor, without the use of antibiotics. Demographics, maternal morbidity, operative difficulties and postoperative complications were compared. Statistically significant differences in patient demographics include a higher maternal age in the C-HYST group than for those in the C-BTL group (31.0 +/- 5.8 versus 27.7 +/- 5.4 years; p = 0.002). C-BTL patients had higher gestational ages (39.4 +/- 1.6 versus 38.7 +/- 1.3 years; p = 0.0017). The C-HYST group had a higher estimated blood loss (1,201 +/- 472 versus 718 +/- 364 milliliters; p = 0.001), change in hematocrit level (6.0 +/- 4.4 percent versus 4.5 +/- 3.4 percent; p = 0.013) and operating time (115 +/- 37 versus 74 +/- 26 minutes; p = 0.0001). Blood transfusion was similar in both groups. Febrile morbidity was higher in the C-BTL group (68.0 percent versus 50.0 percent; p = 0.01). Endometritis was the significant determinant of febrile morbidity for the C-BTL group (41.7%) and cuff cellulitis in the C-HYST group (25.6 percent). Intraoperative and postoperative complications between the two groups were rare and not statistically different. Clinical morbidity for C-HYST is not significantly different than C-BTL. Elective C-HYST may be used in place of C-BTL when indications for hysterectomy are present. PMID- 8211579 TI - Regional and systemic immune responses in a murine model of empyema. AB - The extent to which circulating leukocytes reflect functional capacity at the site of infection is unclear despite a century of debate. We conducted experiments designed to clarify those relationships as well as the relationship of pleural and peritoneal responses to infection. Empyema was established in inbred CBA/J mice by introducing Escherichia coli and Bacteroides fragilis into the thoracic cavity through a limited thoracotomy. Walled off abscesses appeared seven days after the introduction of infection. Cell surface expression of murine class II major histocompatibility antigen was measured in peripheral leukocytes, thoracic and peritoneal cavity exudate leukocytes and abscess cells for 60 days after the introduction of infection. The peripheral antibody response was determined by measuring immunoglobulin M (IgM) and immunoglobulin G (IgG) specific for the two organisms. The results demonstrated that, after introduction of infection into the thoracic cavity, mice mounted a specific systemic humoral immune response by producing IgM and IgG. There was a pronounced concomitant cellular response in thoracic and peritoneal cavity exudate cells. However, there was no evidence of a systemic cellular response in circulating lymphocytes or monocytes and polymorphonuclear leukocytes measured as a single group. We conclude from these experiments that measurements of peripheral immune parameters may adequately reveal the humoral response to infection, but it does not reflect the local immune cellular response. Furthermore, a special relationship exists between the peritoneal and the thoracic cavities, whereby an inflammatory process in the thoracic cavity leads to a marked activation of inflammatory process in the peritoneal cavity without affecting peripheral circulating cells to the same extent. PMID- 8211580 TI - Carcinoma of the ampulla of Vater. AB - We reviewed our experience with 69 patients with carcinoma of the ampulla of Vater admitted to the Memorial Sloan-Kettering Cancer Center, New York, from October 1983 to October 1990. Of the 69 patients, 66 were explored and 55 underwent resection (83 percent resectability). The median length of survival for the 55 patients who underwent resection was 51 months, compared with eight months for the 14 patients who did not undergo resection (p = 0.000004). Of the variables evaluated, only resectability was a statistically significant predictor of survival. Positive lymph nodes in 17 of 55 patients who underwent resection were not predictive of long term survival. PMID- 8211581 TI - The effect of nonobstetric operation during pregnancy. AB - The clinical course and pregnancy outcome of all patients undergoing extensive nonobstetric operation during pregnancy during a ten-year period was reviewed. During this time, there were 49,567 births and 78 women had nonobstetric operation; an incidence of one in 635. The most common indications for surgical treatment were appendicitis, adnexal mass and cholecystitis. The perinatal mortality rate was not increased in women undergoing nonobstetric operation, provided that fetal viability was established preoperatively. In this series, there was no measurable benefit from the use of perioperative prophylactic tocolytic agents. However, nonobstetric operation was associated with an increased risk of preterm labor. Postoperatively, patients should be monitored for contractions and treated with tocolytic agents when appropriate. PMID- 8211582 TI - The role of flow cytometry in carcinoma of the colon and rectum. AB - Flow cytometry was performed upon 312 patients with adenocarcinoma of the colon and rectum, satisfactory results being obtained with 275 (108 diploid, 130 aneuploid and 37 tetraploid). The proportion of nondiploid instances increased from 28 percent if one, to 80 percent when six specimens were assessed per patient. Reproducibility of the technique showed substantial agreement in the assessment of deoxyribonucleic acid ploidy (Kappa value equals 0.74). Increasing values of cells in the diving (G2/M) phase of the cell cycle were associated with little lymphocytic tumor infiltration (p = 0.0002) and extensive tumor fibrosis (p = 0.003). Univariate survival analysis revealed that, although diploid tumors tended to have a better prognosis than nondiploid tumors (p = 0.06), no flow cytometric variable was significantly related to survival. Flow cytometry similarly was not of prognostic value in instances without lymph node metastases or without distant metastases. Multivariate regression analysis of flow cytometric and clinicopathologic variables identified Dukes' stage, patient age and tumor differentiation as the combination of variables most closely related to survival. No flow cytometric variable could significantly improve on the prognostic model containing these three variables. It is concluded that conventional histologic variables remain the best predictors of prognosis in carcinoma of the colon and rectum. PMID- 8211583 TI - Infection prevention in patients with severe multiple trauma with the immunomodulator beta 1-3 polyglucose (glucan). AB - In a effect to prevent nosocomial pneumonia and sepsis, we treated patients with severe multiple trauma with an immunomodulator--beta 1-3 polyglucose (glucan). Forty-one patients with no infection at admission were stratified using Trauma Score and included in a randomized double-blind controlled trial. They were divided into a control group (n = 20) and a glucan group (n = 21). Pneumonia occurred in 11 of 20 patients in the control group and in two of 21 recipients of glucan (p < 0.01). Sepsis occurred in seven of 20 patients in the control group and in two of 21 patients treated with glucan (p < 0.05). Considering patients with pneumonia and sepsis, a decrease was observed in nosocomial infection from 65.0 to 14.4 percent (p < 0.001). The mortality rate related to infection was 30.0 percent in patients in the control group and 4.8 percent in the group treated with glucan (p < 0.05). The general mortality rate, cerebral deaths excluded, was 42.1 percent in the control group and 23.5 percent in the glucan group. PMID- 8211584 TI - Blood loss at time of cesarean section by method of placental removal and exteriorization versus in situ repair of the uterine incision. AB - The current study was undertaken to determine if blood loss at the time of cesarean section is affected by method of placental removal (spontaneous versus extracted) or uterine position for repair (in situ versus exteriorized). This prospective randomized study involved 100 women who were undergoing a cesarean section. The patients were placed into one of four groups--1, spontaneous placenta detachment, in situ uterine repair; 2, spontaneous placental detachment, exteriorized uterine repair; 3, manual placental removal, in situ uterine repair, and 4, manual placental removal, exteriorized uterine repair. Patients with spontaneous placental separation (groups 1 and 2) compared with manual removal (groups 3 and 4) revealed a significant decrease in blood loss (p < 0.001). Uterine position did not significantly affect blood loss in the spontaneous group (1 and 2; p = 0.971) or the manual placental removal groups (3 and 4; p = 0.061). The hematocrit values for all groups were similar preoperatively, but postoperatively, were significantly lower in the manual removal groups when compared with the spontaneous placental separation groups (p < 0.001). The method of placental removal and not the position of the uterus at the time of its repair has a significant role in blood loss during cesarean birth. PMID- 8211585 TI - Acute appendicitis and the use of intraperitoneal cultures. AB - We reviewed the charts of 200 patients with a preoperative diagnosis of acute appendicitis (AA) to evaluate the influence and use of intraoperative culture results on patient management and antibiotic selection. Cultures were obtained in 66 percent of patients; 16 percent of the cultures in patients with AA yielded positive results versus 88 percent of cultures in patients with perforated or gangrenous appendicitis (complicated appendicitis [CA]) and in nine patients, positive cultures were used to adjust antibiotic therapy. Patients with CA who had antibiotic changes based on culture results had a complication rate of 25 percent versus a 29 percent rate for this group as a whole. We conclude that intraoperative cultures in patients with AA are rarely positive and do not influence antibiotic therapy or patient management. In CA, antibiotic changes based on culture results do not seem to alter patient outcome. Surgeons tend to rely on the proved efficacy of empiric antibiotic therapy and other basic surgical principles to afford the best outcome for their patients. The routine practice of obtaining peritoneal cultures in patients operated upon for AA and CA should be abandoned. PMID- 8211586 TI - Pregnancy after orthotopic continent urinary diversion. AB - Continent urinary diversion has become a common form of bladder management for the female exstrophy patient in whom primary reconstruction has failed. Reported are the results of successful pregnancies in four young adult females, who had previously undergone a flap vaginoplasty as part of earlier management and more recently a continent right colonic urinary reservoir with a perineal stoma (Indiana pouch). Pregnancy in each of these patients was characterized by several urinary tract infections, cervical prolapse and mild to severe maternal hydronephrosis. All of the patients had some degree of difficulty with clean intermittent catheterization. One patient required an indwelling catheter with prolonged bed rest. Maternal hydronephrosis resolved after delivery in all instances. All four patients delivered their infants by way of cesarean section, either emergently for maternal or fetal distress or electively. Cervical prolapse did not resolve in three patients and will require surgical repair. After delivery, all patients returned to their previous pattern of clean intermittent catheterization without loss of continence. All the infants delivered were healthy with appropriate weights and high Apgar scores (more than 8). Orthotopic (perineal stoma) continent urinary diversion is not a contraindication to pregnancy. However, our experience mandates delivery by cesarean section with close monitoring for maternal or fetal distress during gestation. PMID- 8211587 TI - Hangman's tie simplifies seton management of anal fistula. PMID- 8211588 TI - Improving peritoneal venous catheter patency. PMID- 8211589 TI - A technique for portal pancreatic transplantation with enteric drainage. AB - Twelve patients were operated upon using this technique. Early results show that hyperinsulinemia has abated in these patients and that the need for postoperative bicarbonate replacement, admissions for dehydration or hematuria resulting from pancreatic exocrine drainage into the bladder are also eliminated (9). This new technique of portal pancreatic transplantation is suitable for patients undergoing combined pancreatic and renal transplantation in whom rejection of the pancreas can be monitored through the function of the renal allograft. The procedure is technically feasible and safe. However, large trials are needed to document the full benefits and continued safety of this new procedure. PMID- 8211590 TI - Eversion technique for carotid endarterectomy. AB - Since April 1991, we have used the eversion technique to perform carotid endarterectomy in 31 consecutive procedures. There were no operative deaths in the current series, and no neurologic complications have been observed. We believe this technique decreases the possibility of early and late restenosis and recommend it for patients requiring carotid endarterectomy. PMID- 8211591 TI - Open fixation of sternal fracture. AB - Displaced sternal fractures cause extensive pain and may impair ventilatory efforts, particularly in the elderly. Most previous reports have focused on repair of sternal fractures using wires. We recommend the technique of plate fixation described herein. PMID- 8211592 TI - Ductal carcinoma in situ of the breast. AB - DCIS is an early localized stage of mammary malignancy that has an especially favorable prognosis with appropriate management. It seems to be a direct precursor to invasive carcinoma of the breast and has the same therapeutic options. There are still many outstanding issues to be resolved before the intriguing potential of this disease can be fully realized. Any physician involved in the management of diseases of the breast must be committed to a thorough understanding of all aspects of the biologic factors of this entity, so as to be able to rationally provide appropriate advice and treatment. Ongoing investigations should advance the knowledge and experience with this disease in future years. PMID- 8211593 TI - Pseudomyxoma peritonei. AB - Pseudomyxoma peritonei results from implantation of malignant tumors or irritation from ruptured benign cysts. This disease is traditionally characterized by accumulation of mucinous ascites, relatively long survival period and absence of extraperitoneal metastases. Disease progression is difficult to predict because of the spectrum of underlying pathologic entities. Four unusual instances of pseudomyxoma peritonei are presented. An instance of the neoplasm confined to the splenic parenchyma suggests potential for hematogenous dissemination. The tumor can be limited to and extend along the retroperitoneum. Retained rectal tissue after proctocolectomy may be a possible origin of disease. Enterobronchial fistula formation is a serious long term complication. Aggressive surgical approach with resection of the bulk of disease offers the optimal palliation and prognosis. PMID- 8211594 TI - Bladder neck closure with an Indiana stoma outlet as a technique for continent vesicostomy. AB - A continent vesicostomy was performed upon two patients. The opened right colonic segment was used to augment the bladder and the ileocecal portion to create a continent abdominal stoma according to the technique used in the Indiana pouch. One patient had complete obstruction of the urethra 1 centimeter distal to bladder neck. The second patient was a paraplegic with an contractile bladder and complete outlet incontinence who was reluctant to perform transurethral self catheterization. After postoperative follow-up evaluation of 36 and 22 months, respectively, both patients are completely continent day and night on self catheterization every six hours with preserved function of the upper part of the tract. PMID- 8211595 TI - Incidence, management and significance of surgical complications after pancreatic transplantation. AB - Despite recent advances, pancreatic transplantation is still in evolution and is associated with considerable surgical morbidity. We reviewed the surgical complications of 127 consecutive whole pancreatic transplants performed at the University of Iowa between March 1984 and January 1992, to evaluate the impact of these complications on graft and patient outcome. Of these transplantations, 89 were simultaneous pancreatic and renal transplants, 32 pancreas after kidney and six pancreas alone. Of all complications requiring hospital admission, 29 percent were surgical in nature. Graft thrombosis (19 percent), deep wound infection (18 percent), duodenal leak (7 percent) and iliac artery disruption (3 percent) were all associated with significant graft (n = 28) and patient (n = 6) loss. In contrast, recurrent urinary tract infections (20 percent), recurrent pancreatitis (17 percent), superficial wound infections (13 percent) and recurrent hematuria (12 percent) did not affect patient or graft outcome. Surgical complications after technically successful transplants were associated with a 4.9 percent mortality rate and a 4.9 percent graft loss. The overall one year actuarial patient and pancreas graft survival rate was 86 and 75 percent, respectively. Despite ongoing refinements in surgical technique, pancreatic transplantation is still associated with considerable surgical morbidity. However, the outcome is favorable if these complications are managed aggressively. PMID- 8211597 TI - Potential of overuse of the inferior vena cava filter. AB - To examine indications for, and morbidity and mortality rate of, inferior vena cava filter insertion at a community hospital, the records of 69 patients who received inferior vena cava filters were reviewed. Patients were assigned to three groups--group 1, 45 patients with pulmonary embolism or deep venous thrombosis and a contraindication to anticoagulation; group 2, 14 patients with a diagnosis as in group 1, who received filters without consideration to anticoagulation, and group 3, ten patients with clinically suspected deep venous thrombosis and no objective assessment of the process. Indications for filter placement were recorded. Morbidity and in-hospital mortality rates were 29 and 49 percent, 43 and 36 percent and 10 and 30 percent for groups 1, 2 and 3, respectively (29 and 43 percent overall). Only patients in group 1 had documented indications for caval interruption. Results compared unfavorably with complication and mortality rates reported previously. Non-selective use of inferior vena cava filters is associated with unacceptable morbidity and mortality rates. Strict indications for filters must be well documented. PMID- 8211596 TI - Difficulties in diagnosis of carcinoma of the breast in patients less than fifty years of age. AB - Delay in diagnosis of carcinoma of the breast is a significant cause of medical malpractice suits in the United States. Although less than one-third of the patients with carcinoma of the breast are less than 50 years of age, more than two-thirds of these suits involve women less than 50 years of age. To see whether or not there are medical factors that make diagnosis in young women more difficult, we reviewed all patient visits to the East Carolina University (ECU) Breast Clinic between 1 January 1988 and 30 June 1991. Women less than 50 years of age had many more patient visits (1,567 versus 838 visits) and many fewer carcinomas detected (38 versus 100 visits) than women who were more than 50 years old. The sensitivity and positive predictive value of mammography were significantly lower in young women than older women (68 versus 91 percent, p < 0.005, and 28 versus 53 percent, p < 0.001, respectively). Physical examination in young women was also less satisfactory. Tumors were more ill-defined and the percent that were easily palpable were significantly lower (45 versus 72 percent, p < 0.01). Furthermore, there was a basic difference in the reason tumors were not palpable in each age group. In older women, tumors were nonpalpable because they were small (mean size 1.0 versus 4.1 centimeters, p < 0.01), whereas in younger women, the non-palpable tumors were large (mean size 4.0 versus 3.4 centimeters), suggesting that they were not palpable because of background mammary density or diffuse growth pattern rather than size. Data from the Breast Cancer Detection Demonstration Project were analyzed and also suggested that carcinomas are more difficult to diagnose in young women. The percent of carcinomas that were not detectable by either mammogram or physical examination were inversely proportional to age and ranged from 36 percent at 40 years of age to 9 percent at 75 years of age. In addition, data from Blue Cross and Blue Shield and the ECU Breast Clinic indicated that it costs at least twice as much to diagnose each carcinoma in women less than 50 years of age. In conclusion, we believe that currently available techniques for diagnosis of carcinoma of the breast are not satisfactory for women less than 50 years of age and that this, rather than physician error, may account for the large number of malpractice suits in this age group. PMID- 8211598 TI - Pediatric pelvic fractures combined with an additional skeletal injury is an indicator of significant injury. AB - Traumatic fractures of the adult pelvic area have high rates of associated injuries and hemorrhagic complications resulting in significant morbidity and mortality. We studied whether or not the plain roentgenographic identification of other fractures is a reliable marker of increased morbidity and mortality in children with pelvic fractures. The records of 79 children admitted with the diagnosis of pelvic fracture from January 1986 through December 1990 were reviewed. Associated injuries were categorized as head, chest, abdomen or skeletal. The pelvic fractures were grouped using the classification system of Torode. Mechanism of injury, age, weight, vitals on admission, operative procedures performed, amount of blood transfused during the first 24 hours, number of days hospitalized, modified injury severity score (MISS) and revised trauma score (RTS) were recorded for each patient. Using any other bony fracture as an easily identifiable additional risk factor, we recorded the associated injuries in those with pelvic fracture and any additional fracture (PF+AF, n = 39) and pelvic fracture alone (PF, n = 40). The PF+AF group demonstrated a significantly higher incidence of head and abdominal injuries and a significantly higher number of required transfusion in the first 24 hours (Fisher's exact test, p < 0.05). Mortality, thoracic injuries and patients requiring laparotomy or an additional nonorthopedic procedure occurred approximately twice as often in the PF+AF group compared with the PF group. However, the numbers were too small to be statistically significant (Fisher's exact, p > 0.05). The PF+AF group also had a significantly higher MISS and average number of days hospitalized (Student's t test, p < 005). The RTS was significantly lower (p < 0.05). In children with pelvic fractures, we found that any additional bony fracture is a significant marker for head and abdominal injury. This constellation identifies patients who may benefit from early transfer to a regional pediatric trauma center. PMID- 8211599 TI - A review of the results of laparoscopic versus open appendectomy. AB - Proponents of laparoscopic appendectomy emphasize the advantages of laparoscopic operation--decreased hospitalization, paralytic ileus, postoperative pain and wound complications, including infection. This study compared open laparoscopic appendectomy with laparoscopic appendectomy. To compare the two techniques, patients undergoing laparoscopic appendectomy at four hospitals were compared with patients undergoing open appendectomy during a six month period. Excluded were incidental appendectomies and patients with perforated appendicitis. An equal number of pediatric patients undergoing laparoscopic and open procedures were included in the analysis to avoid bias, because most of the laparoscopic appendectomies were performed in the adult patient population (age of more than 16 years). A University Medical Center, a Veterans Administration and two community hospitals were the settings. Patients undergoing laparoscopic appendectomy (n = 54) had an average age of 25.7 +/- 1.5 (range of six to 59 years). These patients were compared with 121 patients undergoing open appendectomy whose average age was 23.7 +/- 1.8 (range of three to 83 years). The race and gender distribution were similar in the two groups. Traditional open appendectomy was compared with a group of patients undergoing laparoscopic appendectomy. Variables evaluated were operating room time, number of patients who reported nausea, days until patient tolerated a regular diet, days of hospitalization, postoperative pain medication and wound infection rate. Results are expressed as the mean plus or minus standard error of the mean. Analysis of variance was used to compute continuous variables and Fischer's exact test was used for discrete variables. The laparoscopic approach was attempted in 61 patients and completed in 54 patients. Open appendectomy was performed upon 121 patients. Nineteen patients (18 who underwent open operation and one patient who underwent laparoscopic operation) were excluded from further analysis because of perforated appendicitis. The open procedure took less time (p < 0.05). However, there were more wound infections than in the laparoscopic group (seven of 103 versus zero of 53; p = 0.09). Patients with acute appendicitis recuperated more quickly from the laparoscopic procedure, as evidenced by the time until eating regular diet, period of hospitalization, incidence of nausea and pain medications on postoperative day one (p < 0.05). The absence of wound infections after laparoscopic appendectomy can be attributed to the practice of placing the appendix in a sterile bag or into the trocar sleeve before removal from the abdomen. Laparoscopic appendectomy reduces the period of hospitalization, postoperative ileus, nausea and postoperative pain in patients with acute appendicitis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8211600 TI - Locally advanced carcinoma of the colon and rectum involving the urinary bladder. AB - We reviewed the records of 70 patients who underwent resection of a carcinoma of the colon and rectum with en bloc total cystectomy (36 patients) or partial cystectomy (34 patients) because of tumor directly extending into the urinary bladder. Preoperative genitourinary symptoms were present in 33 of the 70 patients (41.7 percent) and were highly predictive of malignant invasion of the bladder (97.0 percent). Duration of catheter drainage after partial cystectomy correlated with early postoperative bladder function; all 25 patients who had the catheter remain in place at least ten days had normal voiding after catheter removal, while five of nine patients whose catheter was removed before ten days had retention requiring catheter reinsertion (p < 0.01). Urologic complications occurred in two patients after total cystectomy and in three patients after partial cystectomy. There were three postoperative deaths in the total cystectomy group but none after partial cystectomy. Sixty-four patients with negative resection margins had a median survival period of 34 months and a five-year actuarial survival rate of 51.8 percent. In contrast, the median survival period for six patients who had positive margins was 11 months, with no survivors at five years. PMID- 8211601 TI - Detection of epidermal growth factor and transforming growth factor alpha protein in meningiomas and other tumors of the central nervous system in human beings. AB - Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are potent mitogens for normal cells of ectodermal and mesodermal origin. Evidence is accumulating that suggests that EGF, TGF alpha and their common receptor (EGF/TGF alpha-R) influence development and functioning of tissues of the central nervous system (CNS). To further investigate the possible roles of EGF, TGF alpha and their receptor in autocrine/paracrine regulation of tumor growth in the CNS, a series of tumors of the CNS were analyzed for the presence of specific, high affinity EGF/TGF alpha receptors and for the presence of immunoreactive TGF alpha protein. Binding of 125I-EGF to crude membranes from a pool of meningiomas was competed for equally well by low concentrations of unlabeled EGF or TGF alpha, but not by high concentrations of other protein hormones, demonstrating the high degree of specificity of the EGF/TGF alpha receptor. Specific binding of 125I-EGF was dependent upon time and temperature, with maximum specific binding achieved after two hours at 22 degrees C. Scatchard analysis of six tumors of the CNS large enough to permit titration analysis generated linear plots with an average kilodalton of 1.1 +/- 0.1 nanometer (+/- standard error of the mean), suggesting the presence of a single class of EGF/TGF alpha-R with high affinity. EGF also stimulated phosphorylation of a 170 kilodalton protein in membrane fraction of a meningioma, demonstrating that the EGF/TGF alpha-R in this tumor retained EGF-stimulated kinase autophosphorylating activity. Membranes for 17 additional smaller tumors of the CNS were analyzed for specific binding of 125I-EGF by single, high concentration method, and all 17 tumors were found to contain specific binding of 125I-EGF. The average level of 125I-EGF for all 23 tumors of the CNS was 46 +/- 27 femtomoles per milligram protein with a range of 1 femtomoles per milligram for both a pituitary adenoma and meningioma to 638 femtomoles per milligram for a glioblastoma. A series of 13 tumors of the CNS were analyzed for EGF alpha with use of a specific radioimmunoassay. TGF alpha immunoreactive protein was detected in all four malignant tumors of the CNS assayed at an average level of 2.6 +/- 1.1 nanograms per milligram soluble protein, whereas TGF alpha immunoreactive protein was detected in only two of nine benign tumors of the CNS. These results add support to the hypothesis that TGF alpha and its receptor may act by autocrine/paracrine mechanisms to influence growth of tumors of the CNS in vivo. PMID- 8211602 TI - Patient characteristics, methods of evaluation and treatment of ocular melanoma in the United States for the years 1981 and 1987. AB - The American College of Surgeons performed a patient care and evaluation study of malignant melanoma for 1981 and 1987 to determine the presenting symptoms, methods of evaluation, clinical management and resulting outcome. A previous report on malignant melanoma of the skin has been published. This report details the findings of 245 ocular melanomas in 1981 and 275 ocular melanomas in 1987. Most of the ocular melanomas were uveal. The patients with ocular melanoma were older than the patients with skin melanoma. No significant difference was found in the number of ocular instances by gender and by study year. A high percentage of non-Hispanic Caucasians were documented with this disease, and a high percentage of ocular melanomas were not classified by the standard Callender classification. A significant number of melanomas had pigmentation, and a significant number of patients had imaging studies that, in the absence of an elevated alkaline phosphatase, usually yielded negative results. Most patients were treated with enucleation, with an increase in frequency of radiation therapy from 1981 to 1987. Local and regional recurrence was not a problem, but systemic metastases occurred frequently. Type of histologic factors by the Callender classification had an influence on survival. PMID- 8211603 TI - Diagnosis and therapy of subclinically infected prostheses. AB - We believe 5 to 7 percent of prosthetic devices are "subclinically" infected by Staphylococcus epidermidis. These infections are manifested by chronic pain, migration and late extrusion of the devices. To examine this problem, we cultured penile and mammary prostheses. For the experimental arm, we cultured painful penile and mammary prostheses that were being removed because of symptoms (pain). For patients in a control group, we cultured penile prostheses being replaced because of mechanical failure (no pain) and mammary tissue expanders that were temporarily installed. Actual parts of the device were cultured in Trypticase Soy Broth. There were 14 and 12 painful penile and mammary prostheses, 13 and ten, respectively, were cultured positive, for an infection rate of 88 percent. The primary organism identified was S. epidermidis. The nonpainful penile prostheses (zero of five and three of 22 mammary prostheses) grew S. epidermidis. The differences were highly significant (p < 0.001), suggesting that the painful prosthesis is infected. In an attempt to resolve the problem of the painful prosthesis, ten prosthesis were removed and exchanged for new devices. Patients received preoperative and postoperative antibiotics. All ten had positive cultures and nine of ten were successfully exchanged (no pain). PMID- 8211604 TI - Effects of extracorporeal circulation on blood ketone body ratio reflecting hepatic energy metabolism during cardiac operation. AB - To examine the effects of extracorporeal circulation using an artificial heart and lung machine on hepatic energy metabolism in patients with cardiac operation using hypothermia, the arterial blood ketone body ratio (AKBR) reflecting the hepatic mitochondrial redox state was determined in 12 patients who had undergone cardiac operation using extracorporeal circulation from March to August 1991. Changes in AKBR were compared with those before and after extracorporeal circulation. AKBR decreased significantly after the beginning of extracorporeal circulation (p < 0.001) and remained at a lower level throughout extracorporeal circulation. On termination of extracorporeal circulation, the initial level was immediately resumed. The extent of decrease in ketone body ratio at ten minutes before termination of extracorporeal circulation was correlated with short term postoperative hepatic insufficiency. The patients whose ratio decreased below 0.4 showed increased levels in glutamic-pyruvic transaminase at the end of the first and second week after operation. Changes in AKBR were significantly associated with those in blood pressure (r = 0.433; p < 0.005) and body temperature (r = 0.472; p < 0.005). It was concluded that blood pressure and body temperature influence the blood ketone body ratio during extracorporeal circulation. PMID- 8211605 TI - The use of a disposable laparoscopic trocar for the injection and safe evacuation of echinococcus cysts of the liver. PMID- 8211606 TI - A new technique for gastric pull-through. PMID- 8211607 TI - Enucleation of parotid lymphoepithelial cyst in patients who are human immunodeficiency virus positive. AB - The incidence of benign lymphoepithelial lesions of the parotid gland in patients afflicted with HIV has increased. Enucleation is a safe and effective procedure that provides the patient with complete removal of the cyst and a low recurrence rate. Enucleation of these parotid cysts should be considered in treating these patients. PMID- 8211608 TI - A historical perspective to current review of myocardial protection in cardiac operation. AB - In the discussion of the 1955 landmark study on the first series of open heart operation using the cross-circulation technique, Lillehei stated that, "The solution of many difficult problems in medicine has ultimately been simple and in most cases obvious once sufficient basic knowledge has been brought to bear on the problem." Indeed, a few surgeons have provided the guiding lights in the development of cardiac operation, but it is the acquisition of basic knowledge by thousands of surgeons and basic scientists that have contributed to its goals. PMID- 8211609 TI - To ERCP or not to ERCP? That is the question. PMID- 8211610 TI - Laparoscopic cholecystectomy in high-risk patients. PMID- 8211611 TI - Sociopolitical intrigue in laparoscopic surgery. PMID- 8211612 TI - Practice of endoscopic surgery in Europe. Current state. AB - The outcome of a questionnaire designed to determine the current state of endoscopic surgery conducted amongst members of the European Association for Endoscopic Surgery (EAES) in April to June 1992 is presented. The data received from 266 surgical departments in 26 countries of Europe involved 2,592 staff surgeons of whom 866 practice endoscopic surgery are evaluated. The questionnaire is focused on basic aspects of minimal-access surgery--the motives, the procedures performed, attitudes to training, and different aspects of equipment used. The outcome confirms the presence of a solid beginning for the future development and spread of minimal-access surgery. PMID- 8211614 TI - ERCP in conjunction with LC. PMID- 8211613 TI - Endoscopic retrograde cholangiopancreatography in conjunction with laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy (LC) has become the primary surgical treatment for symptomatic cholelithiasis. In conjunction with the dramatic rise in LC there has been an increase in the number of endoscopic retrograde cholangiopancreatographies (ERCPs) performed. For this study, the records of patients referred to the surgical endoscopy department between January 1991 and February 1992 were reviewed. Seventy-seven ERCPs were performed in conjunction with LC. The indications for ERCP included jaundice or a history of jaundice, gallstone pancreatitis, a suspicious filling defect on either ultrasound or intraoperative cholangiogram, abnormal liver function tests, cholangitis, or postoperative bile leak. Sixty-two procedures were performed prior to LC and 15 procedures after LC. Forty-two patients were female (54.5%) and the patients ages ranged from 14 to 92 years (mean 54.1 years). Of the 62 patients having ERCP preoperatively 35 patients (56.5%) had no evidence of common bile duct (CBD) stones and underwent LC as planned. Twenty-three patients were found to have CBD stones, of which six were referred for an open cholecystectomy and CBD exploration, because of large multiple CBD stones or the presence of a large duodenal diverticulum. Seventeen patients had their CBD cleared endoscopically, and four patients were not successfully cannulated. Fifteen patients had ERCP after LC. There were two patients with CBD injuries who were referred for surgical correction. Two patients had leakage from the cystic duct stump, and four patients had CBD stones, all of whom were successfully treated with endoscopic sphincterotomy. There were four patients who had a normal postoperative ERCP and two patients who could not have their CBD cannulated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8211615 TI - Cholecystectomy. Which procedure is best for the high-risk patient? AB - Laparoscopic cholecystectomy (LC), which results in less postoperative pain, disability, and scarring, has become an attractive alternative method of surgical management of the ambulatory patient with gallbladder disease. The best procedure for severely ill patients who are poor operative risks but require cholecystectomy, however, is unknown since the operative morbidity and mortality of LC in this group of patients had not been studied. All patients (177) undergoing cholecystectomy at one institution were evaluated. Based on their preoperative state of health as defined by a modified acute physiologic score (APS), patients were divided into two groups; one group was defined by an APS of less than 10, indicating they were in good health, and the other had an APS greater than or equal to 10, indicating that the group had multiple risk factors, predicting an increased postoperative morbidity and mortality. Selection for either procedure, LC or open cholecystectomy (OC), was made independently of the patient's preoperative status. Patients' past medical histories; demographic, physiologic, and laboratory data; and postoperative complications were evaluated. When all cholecystectomy patients were arranged into the respective risk groups, the age and severity of illness scores (APS) between LC and OC were not statistically different. Intraoperative and postoperative complications were not significantly different when patients undergoing LC were compared to patients undergoing OC. Laparoscopic cholecystectomy was associated with decreased hospitalization when compared to patients undergoing OC. The overall mortality of the patients undergoing OC was significantly greater than those undergoing LC. LC is an acceptable surgical alternative for high-risk patients requiring cholecystectomy. PMID- 8211616 TI - Laparoscopic cholecystectomy for patients who have had previous abdominal surgery. AB - This paper reports 121 laparoscopic cholecystectomies (LC) in patients who had had previous abdominal surgery between June 1990 and August 1992. There were 93 cases with lower abdominal scar (LS) and 28 with upper or umbilicus midline scar (US). For insertion of the laparoscope in the scarred abdomen we use the conventional laparoscopic approach (CLA), the peritoneum perforation under vision approach (PP), and the open laparoscopic approach (OLA). One hundred twenty scarred abdomens were completed successfully. Conversion to an open procedure was required in one case with previous LS, because of injury of the jejunum. One postoperative intraabdominal hematoma was noted and treated with percutaneous catheter drainage. No reoperation was required and no further complications were noted. Patients who had a previous laparotomy had no substantially longer operative time or postoperative hospital stay. Revealing a total complication rate of 1.6%, this study shows that previous abdominal surgery should no longer be considered a contraindication to LC. PMID- 8211617 TI - Laparoscopic cholecystectomy in transplant patients. AB - Acute cholecystitis is a serious condition in transplant patients and elective cholecystectomy is generally recommended when gallstones are found. We reviewed the results of laparoscopic cholecystectomy (LC) in 10 immunosuppressed transplant patients (6 heart, 4 kidney) and compared them to the results of open cholecystectomy performed in 26 transplant patients (14 heart, 11 kidney, 1 kidney/pancreas). The LC group had a 20% incidence of minor complication with no major complications and no deaths. The open-cholecystectomy group experienced 19% minor complications, 23% major complications, and 15% deaths. The average postoperative length of stay for the LC patients was 4.6 days (2 days for the 5 straightforward cases) as compared to 9.1 days after open cholecystectomy (4 days for the 13 straightforward open cases). Oral immunosuppression was stopped prior to operation but could be restarted within 29 hours after operation in the LC patients and 68 h in the open cases. The findings at LC were helpful in assessing whether acute cholecystitis and/or choledocholithiasis was the source of fever, liver-function abnormalities, or pancreatitis in these immunosuppressed transplant patients. We conclude that LC can be performed safely in transplant patients, but that in 10-20% of patients, the operation will be converted to an open procedure. The advantages of LC in these patients are a shorter hospitalization and less delay to resumption of preoperative oral immunotherapy than after open cholecystectomy. PMID- 8211618 TI - A comparison of laparoscopic and open treatment of acute cholecystitis. AB - A retrospective review of 200 patients with acute cholecystitis, half of whom underwent open cholecystectomy and half of whom underwent laparoscopic cholecystectomy, was performed. The two groups were compared for demographic characteristics, operative course, cost of intervention, and surgical outcome. Laparoscopic cholecystectomy for acute cholecystitis was accomplished with an acceptable morbidity and provided an earlier release from the hospital and return to normal activities with a significant economic savings as compared to the traditional open approach. PMID- 8211619 TI - Laparoscopic surgery. Mistakes and risks when the method is introduced. AB - Laparoscopic cholecystectomy and appendectomy are widely accepted in clinical practice. In the initial stage, when the method is introduced, there are a number of mistakes, risks, and complications possible. The surgeons, the staff, the instruments, the anesthetist, and, last but not least, the patient, are among the possible contributing causes. We try to analyze the reasons and conditions leading to possible complications. Complications we have experienced are reported. In our conclusions we try to show how it is possible to avoid severe problems. PMID- 8211621 TI - Changes in splanchnic blood flow and cardiovascular effects following peritoneal insufflation of carbon dioxide. AB - Laparoscopic surgery has rapidly become a popular and widely used technique. Although this procedure has been shown to be generally safe, cardiovascular derangement related to carbon dioxide pneumoperitoneum has been reported. There are few data available on the relationship between systemic and regional hemodynamics in cases of pneumoperitoneum. Changes in splanchnic blood flow and cardiovascular effects following a moderate increase of intraabdominal pressure (IAP) to 16 mmHg during a 3-h period were analyzed in six anesthetized dogs. After insufflation, cardiac output and blood flow in the superior mesenteric artery and portal vein decreased progressively and returned to the preinsufflation values following deflation. Hepatic arterial blood flow did not change significantly, perhaps due to compensatory mechanisms for maintenance of hepatic blood flow. Mechanical compression of the splanchnic capillary beds due to the elevated IAP may possibly reflect the increase in systemic vascular resistance causing the decrease in cardiac output. To prevent this impairment, intermittent decompression of gas during surgical laparoscopy is recommended. PMID- 8211620 TI - The evolution of postoperative ileus after laparoscopic cholecystectomy. A comparative study with conventional cholecystectomy and sympathetic blockade treatment. AB - Our study is prompted by the arrival of laparoscopic cholecystectomy in connection with the evolution of postoperative ileus (PI) and by its avoidance of the intraabdominal handling implied in conventional cholecystectomy. With this aim a prospective, controlled, randomized, and blind clinical trial was designed using 100 patients divided into five groups (n = 20): I, conventional cholecystectomy (CC): II, CC+injection of 20 ml bupivacaine 0.5% into the mesentery root; III, CC + 7.5 mg propranolol i.v. and 0.5 mg neostigmine s.c., postoperatively until the first defecation; IV, II+III; and V, laparoscopic cholecystectomy. The shortest period of PI was observed in group V. This period increases notably in group IV (53 h), group II (72 h), and group III (84 h) relative to the control group with (89 h). This reduction in PI time runs parallel with an improvement in the patient's general state of well-being. We concluded that after laparoscopic cholecystectomy PI is nonexistent. Furthermore, this study confirms the correlation between the avoidance of intraabdominal manipulation and the evolution of postoperative ileus. PMID- 8211622 TI - Improved visibility of black surgical needles in laparoscopic surgery. AB - Black needles were compared to silver needles for quantity of reflected light and ease of laparoscopic visualization. The black needles reflected less light and were thus more easily visualized during laparoscopic surgical procedures. The silver needles resembled a mirror in that they reflected incident light from both the light source and light from the surrounding tissue. PMID- 8211623 TI - Initial clinical experience with a bipolar snare for colon polypectomy. AB - A bipolar snare was used for colon polypectomy in 86 instances in 61 patients. There were 20 pedunculated polyps ranging in size from 0.3 to 1.5 cm and 66 sessile polyps ranging in size from 0.3 to 4.0 cm. The power output selected ranged from 16 to 30 W on a bipolar electrosurgical generator. No perforation, transmural burn, or post-polypectomy bleeding was encountered. Minimal immediate oozing from a polypectomy stalk required iced-saline lavage but was easily controlled. The bipolar snare is a useful and safe addition to the endoscopic surgeon's armamentarium. PMID- 8211624 TI - 3-D vision technology applied to advanced minimally invasive surgery systems. AB - Current-generation vision for laparoscopic surgery involves flat two-dimensional display on a video monitor; this approach makes it difficult to accurately place the tip of a surgical instrument in the three-dimensional real space of the patient. The surgeon must rely on motion parallax, monocular cues, and other indirect evidence of depth to judge accurately the correct spatial relationship of objects in the field of view. Stereoscopic video can return accuracy to the surgeon. Critical elements in creating stereovision are the biophysical laws governing field of view, focal point, depth of field, accommodation, and convergence. In addition, engineering constraints must be followed, such as fitting a 10-mm port, which are compatible with current systems and economic feasibility. There are two methods for 3-D vision under development which are variations on the same theme of modifying standard laparoscopes by using lenses, mirrors and prisms, and optical shuttering. One method uses two video cameras to simultaneous capture two separate images from a paired optical system. Each image is alternately transmitted to the video monitor (field sequential video) and viewed with electronic or polarizing glasses for a 3-D image. Another method uses a standard laparoscope, optically splits this one image into alternating right/left images, and reconstructs the image as above. A major challenge for both systems is that the distance between the optical elements in the laparoscope is not greater than 10 mm apart and fixed, whereas the human interpupillary distance is greater than 650 mm and can accommodate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8211625 TI - Bile leakage after biliary tract surgery. A laparoscopic perspective. AB - The incidence of bile leaks has increased with laparoscopic cholecystectomy as compared with open cholecystectomy. Minor bile leaks are not infrequent but are clinically insignificant; of the major bile leaks the most common sequela is the biloma, the most serious, bile peritonitis. Early symptoms may be very subtle; all untoward symptoms should be investigated with a HIDA scan to rule out bile leakage. Positive HIDA scans should be followed with endoscopic retrograde cholangiography (ERC) or percutaneous transhepatic cholangiography (PTC). Management of the leakage depends on identification of its source. Prompt identification of ductal injuries permits earlier effective treatment and consequently less morbidity and/or mortality. PMID- 8211626 TI - Strategies for the prevention of laparoscopic common bile duct injuries. AB - There have been many recent reports regarding the safety of laparoscopic cholecystectomy. Common bile duct injury is considered the most significant complication. Regional tertiary centers are reporting a dramatic increase in the number of referrals for management of injuries to the common bile duct following laparoscopic cholecystectomy [22]. The high incidence of injuries has been attributed to problems inherent to the laparoscopic technique or to such secondary factors as inexperience, inadequate instruction, insufficient caution, or patient selection. In response to these numerous reports, the New York State Department of Health has recently implemented credentialing and privileging guidelines for laparoscopic surgery [11]. The purpose of this review is to assimilate the current literature on when and why common bile duct injuries occur in order to present possible strategies for their prevention. PMID- 8211627 TI - Laparoscopic oversewing of a bleeding Mallory-Weiss tear under endoscopic guidance. AB - Continuous bleeding from a Mallory-Weiss tear required laparoscopic surgery to halt the bleeding. The oversewing of the laceration at the esophagogastric junction was readily performed under video control with endoscopic guidance and the bleeding ceased. To stop bleeding from such a tear, we prefer to use this modern approach. PMID- 8211628 TI - Thoracoscopic resection of mediastinal cystic schwannoma. AB - Mediastinal cystic schwannoma is of very rare occurrence. Our patient came with chest pain of 6 months duration. Abnormal shadow on chest x-ray was found. A sharp dissection space was evident by computed tomography (CT-scan) and magnetic resonance imaging (MRI) between the tumor, the left pulmonary artery, and the descending aorta. The patient underwent surgical removal using thoracoscopic surgery. Postoperative discomfort was markedly reduced and hospitalization short. We can conclude that interventional thoracoscopy is a safe, well-tolerated procedure, with excellent therapeutic potentials. PMID- 8211630 TI - An attempt at a percutaneous retroperitoneoscopic approach to ureterolithotomy. AB - The extensive laparoscopic tubectomy programs organized by the Indian government during 1978-1981 as a measure to curb the population explosion brought some unanticipated problems for the authors. One of these, surgical emphysema, gave the authors the opportunity to explore laparoscopically extraperitoneal appearances. So deliberate retroperitoneal surgical emphysema was created, to isolate the ureter so as to locate the stone in it, and to study the feasibility of its removal via laparoscopy itself. The procedure entails minimal trauma and gives the considerable advantage of clear vision for total removal of stone(s). This procedure offers an alternative to the conventional method and to other, newer methods. The conventional method involves wide exposure with attendant morbidity and prolonged hospital stay. Other newer methods require high-tech multimode prerequisites, such as a extracorporeal shock-wave lithotriptor, ultrasound, screening, software, endourological instruments (including lithotriptor), necessarily supplemented by technical experts in each field. Hence such methods require an institutional arrangement at an exorbitant cost to the patient. PMID- 8211629 TI - Laparoscopic cecopexy for cecal volvulus. Case report and a review of the literature. AB - A case of intermittent cecal volvulus in an immunocompromised patient is presented. This patient, whose bowel was viable, was managed successfully by laparoscopic cecopexy. As a clinical entity, cecal volvulus usually presents as either an unrelenting process, culminating in gangrenous bowel, or as an intermittent, recurrent condition with spontaneous resolution but which also may lead to loss of intestinal viability. Surgical management is required in almost every case; however, a review of the literature reveals considerable controversy as to what constitutes the best operation for cases in which the bowel is viable. The most appropriate operation is usually dictated by the clinical circumstances, and in many settings cecopexy is a satisfactory choice of procedure; resection is obviated, bowel need not be opened, and the operation can be performed laparoscopically relatively rapidly. PMID- 8211631 TI - Heller laparoscopic cardiomyotomy with antireflux anterior fundoplication (Dor) in the treatment of esophageal achalasia. AB - The technique of Heller laparoscopic myotomy with associated Dor anterior fundoplication for the treatment of esophageal achalasia is described. This operation was performed on three patients with clinical, radiologic, and manometric diagnoses of achalasia. Complete relief of dysphagia and modifications of radiological and manometric patterns were achieved in all patients 1 month after surgery. Laparoscopic treatment of achalasia is technically feasible, reduces surgical trauma, and may be considered a valid alternative to open surgery. PMID- 8211632 TI - Surgery 2001. Concepts of telepresence surgery. PMID- 8211633 TI - Laparoscopic instrument grips. An ergonomic approach. PMID- 8211634 TI - Use of ultrasound to identify the ureter. PMID- 8211635 TI - The significance of Otfrid Foerster's work for the Deutsche Gesellschaft fur Neurochirurgie. PMID- 8211636 TI - An observation of the third ventricle under flexible fiberoptic ventriculoscope: normal structure. AB - The third ventricle, which is deeply seated in the center of the brain, is one of the most inaccessible regions from which to obtain information before surgery. A new flexible fiberoptic endoscope for examination of the ventricles is presented herein. The main advantages of this new device over existing fiberoptic instruments are the extended flexibility of the tip and its small diameter. Using this endoscope, one can observe the third ventricle in situ in patients with hydrocephalus associated with various lesions. The neural and vascular structures in the inner wall of the third ventricle are also illustrated. PMID- 8211637 TI - Surgery, hyperfractionated craniospinal irradiation, and adjuvant chemotherapy in the management of supratentorial embryonal neuroepithelial neoplasms in children. AB - Supratentorial embryonal neuroepithelial tumors are undifferentiated neoplasms. We have used this term in preference to the controversial classification primitive neuroectodermal tumors (PNET). These lesions in children are malignant neoplasms which are usually fatal within 2 years of diagnosis in spite of therapy with surgery, radiotherapy, and chemotherapy. We have adopted an aggressive approach to the treatment of these tumors with surgical resection, hyperfractionated craniospinal irradiation of 30.6-43.9 Gy followed by a tumor boost to a total dose of 50-63.7 Gy, and adjuvant chemotherapy with cyclophosphamide, vincristine, and cis-platinum. We have treated five children, aged 4-18 years, with this approach. In contrast to the results reported in the literature, four children are alive without evidence of tumor from 4.3 to 8.0 years following diagnosis. One has suffered a tumor relapse at 2.3 years following diagnosis but remains alive. The basis of our therapeutic strategy for childhood supratentorial embryonal neuroepithelial tumors and the implications of our clinical results are discussed. PMID- 8211638 TI - Immunohistochemical detection of carbohydrate determinant 19-9 (CA 19-9) in intracranial epidermoid and dermoid cysts. AB - We evaluated carbohydrate antigen (CA) 19-9 levels of intracranial dermoid and epidermoid cyst in serum and intratumoral tissue. The preoperative serum levels were mildly to moderately higher than their normal ranges in four of seven patients. In four patients with high serum CA 19-9 levels, they returned to normal ranges in three who had the cyst resected totally and remained slightly high in one with residual cyst. Immunohistochemical studies using anti-CA 19-9 antibody demonstrated positively stained capsule and keratinous tissue. Serum CA 19-9 levels of intracranial dermoid or epidermoid cysts with more teratomatous components may be elevated above normal levels. PMID- 8211639 TI - Hypothermic circulatory arrest and the management of giant and large cerebral aneurysms. AB - The surgical adjuncts of hypothermic circulatory arrest, exsanguination, and barbiturate cerebral protection were evaluated in nine cases of cerebral aneurysms felt unapproachable by conventional surgery. These techniques were used in seven posterior circulation aneurysms, two of which were giant and two giant anterior circulation aneurysms originating at the middle cerebral artery bifurcation. Four patients had excellent outcomes, two had a fair result, one had a poor result, and two died. The outcome of surgery reflected that of the management of patients with unruptured or ruptured aneurysms. Three of the four patients who did well had unruptured aneurysms, and all three of the cases in which death or a poor outcome resulted occurred in patients presenting with subarachnoid hemorrhage. The rationale for the use of hypothermic circulatory arrest is discussed, and the surgical indications, techniques, and anesthetic considerations are also reviewed. PMID- 8211640 TI - Neurosurgical navigation using a noninvasive stereoadapter. AB - A neurosurgical navigation system incorporating a multiarticulated arm and an isocentric stereotaxic mechanism has been developed. The usefulness of the navigation system has been increased by using it in combination with Laitinen's noninvasive, accurately reproducible stereoadapter. Stereotaxic microsurgery and surgical navigation was performed successfully in 30 cases with these systems. PMID- 8211641 TI - Cerebral circulation in moyamoya disease: a clinical study using transcranial Doppler sonography. AB - Transcranial Doppler sonography was performed on eight patients diagnosed as Moyamoya disease. Angiographically, the patients-four adults (mean age 42) and four children (mean age 7.7)-underwent a complete six- or five-vessel angiographic study. The results showed the following: (1) Despite the presence of stenosis, all middle cerebral arteries showed very low-flow velocity compared to their ipsilateral distal internal carotid arteries. In adult cases, the difference was very significant (p < 0.02). (2) Relatively high-flow velocity was observed in the posterior cerebral arteries of children, and in the ophthalmic arteries of adult cases. (3) In several occasions, very low-flow velocity values were still detected despite the fact that with angiography, the respective arterial segments were hardly opacified. The relation and discrepancy between these results and the angiographic findings, and the potential application of transcranial doppler in assessing and grading the severity of moyamoya disease are discussed. PMID- 8211642 TI - Cerebral retroflexion in holoprosencephaly developed following ventriculo peritoneal shunting: a case report. AB - Retroflexion of the hypoplastic fused cerebrum is a rare condition in holoprosencephaly. We describe a new case of this entity in a 7-year-old boy with alobar holoprosencephaly whi developed retroflexion of the holosphere 7 years after a ventriculo-peritoneal shunt was placed. The radiological findings revealed retroflexion of the cerebrum anchored to the cranial vault between the precerebral space and the dorsal sac, which were open to each other. In patients with holoprosencephaly, the possibility of retroflexion of the holosphere should be considered after placement of a ventriculo-peritoneal shunt for associated hydrocephalus. PMID- 8211643 TI - Intraorbital arteriovenous malformation: case report. AB - A case of intraorbital arteriovenous malformation presenting with visual loss, exophthalmos, and chemosis of the right eye is reported. Enhanced computer tomography and magnetic resonance imaging showed extraocular muscle enlargement and vascular abnormality in the right retrobulbar space. Angiography revealed an abnormal intraorbital vascular stain with an extremely dilated right ophthalmic artery. Total removal of the intraorbital contents was performed after unsuccessful endovascular and surgical treatment of arteriovenous malformation (AVM). Histopathological examination disclosed an AVM in the retrobulbar fatty tissue with extension into the extraocular muscles and optic nerve. PMID- 8211644 TI - Cerebral aspergillosis in immunologically competent patients. AB - Aspergillosis of the central nervous system is a rare disease, especially if the patient's immune system is not compromised. The authors report three cases of cerebral aspergillosis in the immunocompetent state: a rhinocerebral form in a diabetic patient, a direct extension from chronic Aspergillus otitis media, and a postoperative Aspergillus brain abscess after brain tumor surgery. In spite of the poor prognosis of cerebral aspergillosis, two of the patients survived. The pathogenesis, predisposing factors, radiologic findings including magnetic resonance image, and the outcome are presented. The pertinent literature of cerebral aspergillosis is also reviewed. PMID- 8211645 TI - Aneurysmal bone cyst of the occipital bone: case report. AB - A 21-year-old male with a painful, expanding mass in the occipital bone was operated on. The clinical findings were suggestive of a malignant tumor. However, appearance and histological examination of the operative specimen identified it as being an aneurysmal bone cyst, a rather rare nonneoplastic lesion of unknown origin. Besides demonstration of the case, a review of the relevant literature is presented. PMID- 8211646 TI - Cerebellar hemorrhage complicating supratentorial craniotomy: report of two cases. AB - One of the rare complications of supratentorial craniotomy is the occurrence of a hematoma in the cerebellum. Only seven previous cases have been published, and these have been ascribed to disturbed blood coagulation or decreased intracranial pressure. We present two similar patients, in whom, however, the pathogenetic role of these factors seems improbable. PMID- 8211647 TI - Skull base approaches to complex cerebral aneurysms. AB - The authors used skull base approaches to improve the surgical treatment of cerebral aneurysms. These approaches facilitate aneurysm surgery by allowing early proximal and distal vascular control, shortening and widening of the operative field, increasing the range of the surgeon's operative view and motion, and alleviating brain retraction. Twenty-two patients with ruptured giant or complex aneurysms were operated upon acutely using skull base approaches appropriate for their location: (1) the orbitocranial approach for anterior circulation, ophthalmic artery, and intracavernous lesions (n = 10); (2) the orbitozygomatic approach for aneurysms of the upper third of the basilar artery (n = 6); (3) the petrosal approach for aneurysms of the middle third of the basilar artery (n = 2); and (4) the far lateral-transcondylar approach for vertebrobasilar aneurysms (n = 4). Clipping and dissection of the aneurysms was facilitated by the skull base approaches. No surgical mortality occurred in this series of patients; transient cranial nerve paresis was the only morbidity related to the approaches. We compare the three-dimensional spatial geometry of skull base and conventional approaches, and discuss the advantages and nuances of skull base approaches. PMID- 8211648 TI - Spine surgery and the neurosurgeon. PMID- 8211649 TI - Protrusion of the first thoracic disk. PMID- 8211650 TI - Cerebral berry aneurysms in identical twins. PMID- 8211651 TI - Chordomas and chondrosarcomas involving the cavernous sinus: review of surgical treatment and outcome in 31 patients. AB - During the last 9 years, 31 patients with chordomas (20 cases) and chondrosarcomas (11 cases) involving the cavernous sinus have been treated using an aggressive surgical approach. On the basis of postoperative magnetic resonance imaging (MRI), 17 patients were considered to have undergone total removal, whereas in the remaining 14 cases the tumor was either subtotally or partially removed. Surgical complications were most commonly encountered among patients who had undergone previous operations. One patient died 3 months after the operation as a result of pulmonary embolism. Significant disability occurred in one patient because of thalamic perforator occlusion and hemorrhage. Recovery of extraocular muscle function was gratifying, and correlated to the preoperative functional level. After a median follow-up of 24 months, three recurrences (21%) occurred among the 14 patients who had undergone incomplete removal. No recurrence was observed among the 17 patients with total resection. This experience shows that gross radical removal of chordomas and chondrosarcomas involving the cavernous sinus can be accomplished with an acceptable surgical morbidity. However, much longer follow-up will be required to determine whether such aggressive surgical treatment results in cure or long-term control of these neoplasms. PMID- 8211652 TI - Cerebrovascular bypass surgery for the treatment of Moyamoya disease: unsatisfactory outcome in the patients presenting with intracranial hemorrhage. AB - While the efficacy of cerebrovascular bypass surgery for Moyamoya disease with ischemic events has been substantiated, the surgical indication for the patients presenting with intracranial hemorrhage is as yet undetermined. In an effort to prevent rebleeding from rupture of Moyamoya vessels, seven patients with intracranial hemorrhage underwent indirect bypass surgery. During the follow-up period between 2 and 11 years (mean 4.9 years), one patient suffered rebleeding 5 years after bypass surgery. Follow-up cerebral angiography failed to show revascularization and reduction of moyamoya vessels in all but one of seven patients. Thus, the author's experience suggests that bypass surgery for Moyamoya disease with hemorrhage is angiographically far less successful compared to that with ischemia. A review of the series including patients with angiographically successful revascularization and reduction of Moyamoya vessels failed to demonstrate the definitive effectiveness in eliminating the risk of further intracranial hemorrhage. PMID- 8211653 TI - Meningitis following fractures of the paranasal sinuses: accurate, non-invasive localization of the dural defect by direct coronal computed tomography. AB - A consecutive series of 30 patients admitted with non-meningococcal meningitis is presented. In all there was a history of preceding head injury. All 30 patients were investigated by direct coronal computed tomography (CT) scan to determine whether or not a site of fracture into a paranasal air sinus could be demonstrated. We postulated that such a fracture would correspond to the site of a dural tear. Direct coronal CT demonstrated a fracture in all patients, and this corresponded to the site of a dural tear at operation in every case in which an operation was carried out (28 out of the 30 patients). We propose that this method of investigation is superior to other techniques that have been, or are currently, employed in this clinical situation. PMID- 8211654 TI - Chemotherapeutic effects of intra-arterial administration of ACNU in primary intracerebral non-Hodgkin's lymphoma. AB - The authors report five patients with primary intracerebral non-Hodgkin's lymphoma who were treated with several cycles of intra-arterial injection of 1-(4 amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) at doses of 80 to 100 mg/m2/injection at several monthly intervals. There was no simultaneous use of steroids, and no patients had concomitant immunosuppression; no patient was human immunodeficiency virus positive. This therapy was initially used in four patients with advanced recurrent lymphoma. These patients experienced tumor progression despite our institutional standard therapy comprising cranial irradiation followed by repeated courses of systemic multi-agent chemotherapy (cyclophosphamide, vincristine, adriamycin, and prednisolone) more than 3 months previously. Based upon brain computed tomography scans and clinical neurologic examinations, three of the four cases showed partial responses ranging from 10 to 12 months in duration, whereas the other patient remained stable without worsening for 8 months. A fifth case was particularly noteworthy; this patient had no prior therapy and intra-arterial chemotherapy alone induced an 18-month, disease-free remission. No significant therapy-related complications nor neurotoxicity were seen. These results suggest that intra-arterial administration of ACNU may be a potential candidate for intracerebral lymphoma therapy. PMID- 8211655 TI - The paradoxical blood pressure-flow relationship in the brain with an arteriovenous malformation. AB - The responses of regional cerebral blood flow (CBF) to decrease in arterial blood pressure were studied in eight patients with arteriovenous malformations using the Xe-133 inhalation method. Measurements were performed twice for each study; before and during hypotension induced by trimethaphan camsylate (Arfonad). In all cases, there were regions where cerebral blood flow increased remarkably in response to hypotension. When the studies were repeated in five cases after total resection of the malformations, increase in the cerebral blood flow in response to hypotension was not observed. The underlying mechanisms that operate in such paradoxical blood pressure-flow relationship are discussed. PMID- 8211656 TI - Cervical intervertebral disc prolapse associated with traumatic facet dislocations. AB - Closed reduction of dislocated facet joints is considered safe by most authors. We report the occurrence of traumatic cervical disc prolapse associated with these injuries in four patients. Without adequate radiological exclusion of this pathology, reduction may have catastrophic consequences as illustrated by two of our cases. Anterior discectomy and open reduction and fixation provide safe and successful avenues of treatment. PMID- 8211657 TI - Anterior communicating artery aneurysm rupture: an unusual cause of acute subdural hemorrhage. AB - A case of acute subdural hemorrhage caused by rupture of an anterior communicating artery aneurysm is presented. The patient is a young man who presented with an acute onset of neurologic symptoms; computed tomography revealed subdural hemorrhage in the absence of associated subarachnoid or intraparenchymal bleeding. PMID- 8211659 TI - Cylindrical spinal meningioma. A case report. AB - A case of cylindrical spinal meningioma is reported. This most unusual morphology suggested a preoperative diagnosis of either lymphoma, metastatic epidural tumor, or meningioma. At operation, the tumor was found to be hard and extremely adherent to the cord, so its anterior part had to be left in place. Transient paraplegia was observed postoperatively, but the patient recovered normal stance and gait within 6 months. Three years after the operation, magnetic resonance imaging demonstrated a very slow progression of the remaining tumor with an estimated increase of 5%. The differential diagnosis of this lesion by magnetic resonance, its clinical postoperative evolution, and the surgical strategy are discussed. PMID- 8211658 TI - Systemic metastasis of medulloblastoma through ventriculoperitoneal shunt: report of a case and critical analysis of the literature. AB - An unusual case of medulloblastoma metastasizing through a ventriculoperitoneal shunt to the scrotum in a child with a hydrocele is presented. A review of the literature disclosed 160 cases of medulloblastoma with systemic metastases, 30 (18.7%) of them having undergone systemic shunts. Analysis of the distribution patterns of the metastases in relation to the shunt type revealed that shunts had probably provided the route of systemic spread in no more than 11 cases (6.9%). Only one of these cases had no intracranial tumor at autopsy, suggesting that the outcome was probably worsened by the systemic metastases through the shunt. In contrast, five patients had intraaxial tumor recurrence that largely determined the outcome. In the remaining five cases, information concerning the tumor within the central nervous system was not available, and it remains speculative whether these patients could have survived longer without the shunts. It is concluded that the chance of medulloblastoma metastasizing through cerebrospinal fluid shunt is quite small and has an even smaller chance of adversely affecting the final outcome of the medulloblastoma patient. Consequently, in our opinion there should be no contraindication to precraniotomy shunting if required in such patients. PMID- 8211660 TI - Spontaneous rupture of craniopharyngioma cysts. A report of five cases and review of the literature. AB - Reports of spontaneous rupture of a craniopharyngioma cyst are extremely rare. Five cases of spontaneous rupture of a craniopharyngioma cysts are reported. Clinical symptoms included chemical meningitis in three patients, alleviation of headache in one, and improvement in a visual disturbance in one. Reduction in cyst size was confirmed by computed tomography or magnetic resonance imaging in three of five patients, and the histopathological diagnosis was confirmed histologically in four patients. Cerebrospinal fluid findings were abnormal in the three patients with chemical meningitis. Spontaneous rupture of craniopharyngioma cysts tended to occur more frequently in adult males. Computed tomography and magnetic resonance imaging were useful in diagnosing cyst rupture, and cerebrospinal fluid findings, especially the presence of cholesterol crystals and an elevated cholesterol concentration, are suggestive, even when no reduction in cyst size is observed radiologically. PMID- 8211661 TI - Transnasal illumination to guide the craniofacial resection of anterior skull base neoplasms. AB - The authors describe use of a flexible fiberoptic light source to guide the craniofacial resection of anterior skull base neoplasms. The light is introduced transnasally and serves to outline the perimeter of the tumor, helping to direct the safe placement of intracranial osteotomies and en bloc tumor removal. PMID- 8211663 TI - Primary malignant rhabdoid tumor of the central nervous system: case report and review of the literature. AB - Malignant rhabdoid tumor (MRT) is well known as a pediatric malignant tumor of the kidney. Only nine cases of primary MRT of the central nervous system (CNS) have been reported. We are reporting in detail the clinical course and treatment of a patient with primary MRT of the CNS. We cared for a 3-year-old girl with an MRT that extended from the internal auditory canal to the cerebellopontine angle. Despite three surgical attempts at resecting the tumor combined with whole craniospinal axis irradiation, as well as chemotherapy consisting of intravenous nimustine hydrochloride and intrathecal methotrexate injections, the patient died 13 months after her initial hospitalization. The origin of CNS-MRT development is still a question of pathologic debate. Like renal MRT, the prognosis of MRT of the CNS is very poor. The dissemination of MRT of the CNS occurred in most cases. PMID- 8211662 TI - Stereotaxic radiosurgical ablation: an alternative treatment for recurrent and multifocal hemangioblastomas. A report of four cases. AB - Craniotomy and resection is usually a safe and effective treatment for hemangioblastoma. However, since the surgical removal of recurrent and multifocal tumors can be associated with greater risks, stereotaxic radiosurgery was used to ablate hemangioblastomas in four patients with von Hippel-Lindau disease. In two of these cases a symptomatic lesion was surgically resected just prior to radiosurgery. The 11 radiosurgically treated tumors (four patients) were spherical and varied in diameter from 0.75 to 2.0 cm with a mean of 1.25 cm. Dose ranged from 30 to 75 Gy with a mean of 35 Gy. After a mean clinical and radiologic follow-up of greater than 1 1/2 years, tumor size and/or cyst formation was controlled in all cases. Nevertheless, it was necessary to temporarily shunt a tumor cyst in one patient. In another case, aggressive treatment resulted in symptomatic radiation necrosis. Despite such potential problems we believe that radiosurgical tumor ablation is a reasonable alternative to craniotomy and/or radiation therapy in poor risk patients. This report is believed to be the first published description of the use of radiosurgery in the treatment of hemangioblastoma. PMID- 8211664 TI - Chronic spinal subdural hematoma. AB - A 55-year-old woman with chronic spinal subdural hematoma, diagnosed by magnetic resonance (MR) is presented. There was no coagulation defect, anticoagulant therapy, or trauma. PMID- 8211665 TI - Skull base surgery: too much, too little? PMID- 8211666 TI - Expectations and ideals of the American teacher, 1992. AB - As part of MetLife's series of annual surveys of the American teacher, a cohort of "new" teachers was identified in 1990 and followed over the first two years of their careers. Among these first-time teachers, the level of optimism associated with teaching and the educational environment decreased between 1990 and 1992. This was offset, however, by a fairly strong commitment to the teaching profession and to students as well as to a continued belief that teachers could positively affect the lives of their students. After two years of teaching, 70 percent of the teachers continued to be "very satisfied" with their work experience with students and almost 60 percent were as highly satisfied with their interactions with other teachers. Only 25 percent of the teachers were "very satisfied" with experiences with the parents of their students, however. High school teachers, teachers in inner-city schools and those with the largest proportion of minority and/or low-income students were consistently more negative than teachers in other settings about their ability to make a positive influence on their students' lives. Nineteen percent of teachers thought it likely that they would give up teaching within the next five years. Lack of support or help from students' parents was tied with lack of support from the school administrators as the major reason for leaving the profession. PMID- 8211667 TI - Trends in drug and alcohol use by youth in the U.S.A. AB - For more than a decade, use of most illicit as well as licit drugs has been declining among U.S. high school students. The top four substances used by high school seniors continue to be alcohol, cigarettes, marijuana/hashish and all other illicit drugs combined. Despite decreases in rates of use and laws prohibiting sale to minors, not only is alcohol drinking widespread among high school seniors, but the dangers of use are not appreciated. In 1992 more than half of seniors used alcohol in the past month; 28 percent reported binge drinking and less than half felt great risk was associated with consuming five or more drinks at least once during a weekend. Drug use among elementary school students has also generally decreased since the late 1980s. Between 1987 and 1990, there was a significant decrease in the perceived use of beer, wine and hard liquor by these students but a less pronounced decrease evident for drinking wine coolers. In 1990 about half of sixth graders indicated "some" or "a lot" of peer pressure to try alcohol. Pressure to try wine coolers increased from 46 to 49 percent between 1987 and 1990 among 4-6 graders, and 29 percent of these children said many of their friends had already tried these substances. For more than half of these young students, the school was the main source of their information about the dangers of alcohol and/or drug use in 1990. PMID- 8211668 TI - Diverse living arrangements of children. AB - In the United States, over the past few decades, the prominence of the traditional two-parent family has gradually faded, with its place usually being taken by homes headed by a mother. Relatively few children are raised by single fathers. The pattern of this ongoing development varies considerably by major racial groups as well as by age of child. Current living arrangements for children by three classes of age, race and presence of parents were analyzed by four parental characteristics--age, educational attainment, labor force participation and existence of other siblings. Racial similarities and differences--some significant--are noted. For example, among white children, 36 percent of those under age six had a parent under age 30. Among black children, the proportion was 57 percent and among Hispanics, 46 percent. In all groups, educational attainment was higher in families with two parents. Parents' educational levels were parallel with their employment rates. PMID- 8211669 TI - Record high life expectancy. AB - Expectation of life at birth in the United States rose to a record high of 75.7 years in 1992. Life expectancy for newborn boys and girls also established new peaks, namely 72.2 years and 79.1 years, respectively. Just as noteworthy has been the recent marked reduction in the racial longevity gap. The narrowing in the expectation of life differential between whites and nonwhites resulted from the larger gains among people of color. Also encouraging is the continued decline in infant mortality--it fell to its lowest level ever (8.5 per 1,000 births). However, the outlook for AIDS mortality is disconcerting. Because of the mounting toll of these deaths, there will be a negative impact on expectation of life sometime in the near future. PMID- 8211670 TI - Communication networks for medical image transmission. AB - Digital communication networks are of increasing importance for data exchange in health care environments. They may be used to transmit multi-media data, such as text, images, graphics, signals and sound. The essential characteristics of modern network technologies are summarized in this article and are seen in the context of local, metropolitan and wide area networks. Standardized technologies discussed are Ethernet, token oriented systems, FDDI, DQDB and ATM. Off-line communication media based on magnetic optical disk, such as IS&C, are briefly introduced. The conclusion reached is that therapy planning for radiation therapy or hyperthermia can make use of communication technologies, for example, to transmit patient images, modelling data and results of distribution calculations of physical phenomena. PMID- 8211671 TI - Alpha/beta value and importance of dose per fraction for the late rectal and recto-sigmoid complications. AB - A total of 203 patients with cancer of cervix stage IIIB, treated by radiation alone were analysed retrospectively for the incidence of late rectal and recto sigmoid complications. The patients were treated with a combination of external irradiation and a single intracavitary insertion during January 1979 to December 1983. The external irradiation was randomised to deliver by four different fractionation regimens having dose per fraction of 2 Gy, 3 Gy, 4 Gy and 5.4 Gy. The doses for various fractionation regimens were matched using the time dose factors (TDF) model. 39 cases of late radiation induced rectal and recto-sigmoid complications were observed. The complication rate increased significantly (p < 0.05) with the size of dose per fraction. Using this clinical data an alpha/beta value of 3.87 +/- 0.74 Gy was estimated for late rectal and recto-sigmoid complications. PMID- 8211672 TI - Radiation therapy of the nasopharyngeal carcinoma. Treatment results and prognostic factors. AB - Between September 1977 and December 1989, 89 consecutive patients of nasopharyngeal carcinoma were treated with radiation therapy. The study comprised of 66 males and 23 females; their ages ranged from 17 to 80 years (mean 55 years). Five-year survival rates according to stage were as follows: stages I and II (n = 10), 90%; stage III (n = 10), 43%; stage IV (n = 69), 47%. The important prognostic factors for predicting poor prognostic in this series, which were shown by stepwise proportional hazard (Cox) model, were the level of lactate dehydrogenase (LDH) and neck node involvement. LDH level also influenced nodal failure (p = 0.0002) and distant metastasis (p = 0.006). PMID- 8211673 TI - Alteration of the blood-brain barrier after irradiation: implication in boron neutron capture therapy. AB - The radiobiological and clinical data concerning the alteration of the blood brain barrier (BBB) after cerebral irradiation are reviewed. Several boron neutron capture therapy (BNCT) programs are at present under study in Europe and in the USA. In these programs, irradiation is considered to be delivered in several fractions, and one could also imagine, in principle, delivering BNCT after a full course of external radiotherapy of the brain. These options raise the question of the alteration of the normal BBB by previous irradiation. Before starting clinical applications, it then becomes necessary to assess the integrity of the BBB after different dose ranges and fractionation schemes, and after different time intervals following irradiation. Extrapolation of the available radiobiological and clinical data suggests that for rather small hydrophilic compounds, such as BSH or L-BPA, an early increase in transport through the BBB may be foreseen after single photon dose larger than 10 Gy or after a full standard radiotherapy regimen. However, there is no evidence that the first fractions of a BNCT application (typically 2 to 4 Gy equivalent per fraction) would increase the permeability of the BBB sufficiently to permit transport of large boronated compounds such as porphyrins or antibodies, or even of smaller hydrophilic compounds such as BSH and L-BPA. It can be concluded that the dose selectivity of BNCT is unlikely to be compromised by early alteration of the BBB due to the first fractions of a typical BNCT fractionated regimen. PMID- 8211674 TI - [Radiation-induced myelitis following accelerated radiotherapy]. AB - We report a case of suspected radiation-induced myelitis after twice-daily irradiation with a cord dose of 45.8 Gy. The 48-year old patient had been irradiated with two daily fractions of 1.8 Gy up to 70.2 Gy for oropharyngeal cancer T4 N2 G3 M0 and achieved a complete remission. The spinal cord received 42 Gy by open fields plus 3.8 Gy scatter irradiation after field reduction. Six months after radiotherapy clinical signs of tetraparesis occurred with two lesions in the cervical cord on MR-images. A complete neurological diagnostic procedure revealed no other causes than suspected radiation damage. This is the only case of radiation myelitis among 90 patients treated twice daily and over 2000 patients irradiated with conventional fractionation in the same technique and doses. PMID- 8211675 TI - A letter to the President. PMID- 8211676 TI - Metastatic patterns of invasive lobular versus invasive ductal carcinoma of the breast. AB - BACKGROUND: Many studies have analyzed the metastatic patterns of breast carcinoma. However, very few studies have analyzed the differences in metastatic patterns of lobular versus ductal carcinoma. METHODS: By use of our tumor registry, the metastatic sites of all invasive lobular and invasive ductal breast carcinoma cases during an 18-year period (January 1973 to December 1990) were analyzed. RESULTS: There were 2605 cases of invasive lobular and invasive ductal breast carcinoma. Lobular carcinoma accounted for 359 (14%) and ductal carcinoma for 2246 (86%) of the cases. The percentage of patients with regional lymph node metastasis at diagnosis was not significantly different between the two groups. The rates of metastasis to all lymph nodes, liver, and central nervous system were not significantly different. However, the rates of metastasis to the gastrointestinal system (4.5% vs 0.2%), gynecologic organs (4.5% vs 0.8%), peritoneum-retroperitoneum (3.1% vs 0.6%), adrenal glands (0.6% vs 0%), bone marrow (21.2% vs 14.4%), and lung-pleura (2.5% vs 10.2%) were significantly different (p < 0.05). CONCLUSIONS: The metastatic patterns of lobular and ductal carcinoma of the breast are different, with gastrointestinal system, gynecologic organ, and peritoneum-retroperitoneum metastases markedly more prevalent in lobular carcinoma. Physicians should be aware of these different metastatic patterns of lobular and ductal carcinoma of the breast. PMID- 8211677 TI - Magnetic resonance angiography and duplex imaging: noninvasive tests for selecting symptomatic carotid endarterectomy candidates. AB - BACKGROUND: This report describes our experience with the use of duplex imaging and magnetic resonance angiography (MRA) in the diagnosis and management of 70 patients with symptomatic carotid artery disease. Prospective evaluation of our first 30 patients showed that duplex imaging and MRA accurately correlated with conventional cerebral arteriograms (XRA) in patients with symptoms with greater than 70% ipsilateral carotid artery stenoses. In MRA versus XRA accuracy was 94%, sensitivity 100%, and specificity 93%. With duplex scanning versus XRA accuracy was 88%, sensitivity 93%, and specificity 93%. METHODS: We are now performing carotid endarterectomy on patients with symptoms without preoperative XRA when there is exact correlation between duplex imaging and MRA. Patients must have focal hemispheric symptoms, ipsilateral duplex peak systolic velocity greater than 2 m/sec, and high-quality MRA imaging of the carotid vessels. RESULTS: We have prospectively entered 40 patients for preoperative evaluation with duplex imaging and MRA. High-quality MRA and duplex studies were obtained in 35 patients (88%). XRA was required in the remaining five patients (12%) because of discrepancies between duplex scanning and MRA. Endarterectomy was performed without morbidity or death. Combined use of duplex scanning and MRA eliminated XRA in 35 cases and created a net savings of more than $125,000. CONCLUSIONS: Our experience suggests that preoperative XRA may not be necessary when duplex imaging and MRA confirm the presence of severe extracranial disease. PMID- 8211678 TI - Results of liver transplantation in diabetic recipients. AB - BACKGROUND: The results of orthotopic liver transplantation (OLTx) in patients with diabetes mellitus (DM) are not well defined. METHODS: Between 1985 and 1991, 45 adult patients with pretransplantation DM (5 type I, 40 type II) underwent OLTx at our center as identified by retrospective chart review. We compared this diabetic recipient group to a case-control nondiabetic group matched for age, gender, primary liver disease, weight, and timing of OLTx. A total of 30 variables were collected and analyzed with McNemar's test for categorical data, paired t tests for continuous data, and survival and repeated measures analysis for longitudinal data. RESULTS: No differences between diabetic and nondiabetic recipients were noted in patient or graft survival, the incidence or severity of rejection, blood transfusions, operative complications, readmissions, major infections, or number of hospital days after OLTx. However, the incidence of minor bacterial (p = 0.046) and minor fungal (p = 0.035) infections were higher in the DM group. Serum blood urea nitrogen (p = 0.02) and creatinine (p = 0.03) levels were also higher in patients with diabetes versus control patients during the first year after OLTx. CONCLUSIONS: In carefully selected patients with pretransplantation DM, OLTx can be accomplished with results similar to nondiabetic recipients in spite of a higher incidence of minor infections and renal dysfunction. PMID- 8211679 TI - Comparison of distal and proximal splenorenal shunts: a ten-year experience. AB - BACKGROUND: This study evaluated the effectiveness of distal (DSRS) versus the central or proximal (PSRS) splenorenal shunts in the elective treatment of bleeding varices. METHODS: A series of 48 patients with portal hypertension and established variceal bleeding were randomized to undergo PSRS or DSRS. Preoperative evaluation included endoscopic examination, angiography, serum amino acid profile, liver chemistry studies, and neurologic evaluation. Any patient with significant ascites and hepatofugal flow underwent PSRS shunt procedures; the remainder were randomized prospectively. RESULTS: Between 1979 and 1989, 29 patients underwent PSRS and 19 underwent DSRS. The mean length of follow-up was 48 months. The groups were equivalent with regard to age, gender, child's class, number of preoperative bleeds, and cause of disease. No difference was found in any of the factors measured. In particular there were no differences in the operative mortality rate (17% PSRS; 11% DSRS), 5-year survival rate (52% PSRS; 52% DSRS), rebleeding (34% PSRS; 32% DSRS), shunt occlusion (7% PSRS; 11% DSRS), development of individual episodes of postoperative encephalopathy (28% PSRS; 26% DSRS), chronic postoperative encephalopathy (17% PSRS; 11% DSRS), or mean branched-chain/aromatic amino acid ratios (PSRS = 0.88 +/- 0.05; DSRS = 0.66 +/- 0.05). CONCLUSIONS: The results do not support the contention that DSRS is associated with either greater survival or less encephalopathy than PSRS. PMID- 8211680 TI - Histocompatibility and liver transplantation. AB - BACKGROUND: The role of histocompatibility between donor and recipient in liver transplant rejection is unclear because of a paucity of data. The influence of human leukocyte antigen (HLA) type on immunologic graft loss was examined for primary liver transplantations performed at this center. METHODS: Immunologic graft loss included patient death or retransplantation as a result of rejection or impending graft loss caused by either late hepatic artery thrombosis or severe, unremitting rejection requiring FK 506 rescue therapy. HLA A, B, and DR matching was available on 205 donor-recipient combinations, and an additional 31 patients had A and B matching only. RESULTS: A mismatch of class I antigens (HLA A and B) was predictive of immunologic graft loss (p = 0.018). DR mismatch did not correlate with graft loss. When the A and B loci were analyzed separately, an A mismatch correlated significantly with immunologic graft loss (p = 0.02), in contrast to a B mismatch (p = 0.17). Better matching significantly improved patient survival (p = 0.02) and overall graft survival (p = 0.009). CONCLUSIONS: The beneficial effect of HLA class I antigen compatibility on liver transplantation outcome is in contrast to pancreatic and kidney transplantation in which class II antigen matching but not class I matching is beneficial. Immunologic mechanisms of hepatic allograft rejection may differ from those involved in kidney transplant rejection. PMID- 8211681 TI - Awake patient monitoring to determine the need for shunting during carotid endarterectomy. AB - BACKGROUND: The indications for shunt placement to prevent cerebral ischemia during carotid endarterectomy have been controversial. Some investigators have recommended empiric shunting for patients presumed to be at higher risk for cerebral ischemia with a recent stroke or severe stenosis or occlusion of the contralateral internal carotid artery. METHODS: Carotid endarterectomy was performed in 81 cases with cervical block anesthetic, monitoring the awake patient for the development of cerebral ischemia (unresponsiveness or paralysis) during carotid clamping. The need for shunting (based on awake response) was compared in patients with the arbitrarily defined empiric indications for shunting (n = 29) versus those who did not have such clinical or anatomic findings (n = 52). RESULTS: Cerebral ischemia requiring shunting was observed in five (17.2%) of 29 cases with the defined indications for empiric shunting. This was not different than the need for shunting in the control group where cerebral ischemia was seen in eight (15.4%) of 52 cases. No intraoperative neurologic events occurred in any case, but one (1.2%) patient suffered a postoperative transient ischemia attack and another (1.2%) had a postoperative stroke. CONCLUSIONS: Empiric clinical or anatomic indications for shunting were not reliable predictors of cerebral ischemia that developed during carotid clamping in this study. Awake patient monitoring during carotid endarterectomy with regional anesthetic allowed prompt, accurate identification of patients with cerebral ischemia who would clearly benefit from placement of a shunt. PMID- 8211682 TI - Endorectal advancement flap repair of rectovaginal and other complicated anorectal fistulas. AB - BACKGROUND: Surgical correction of rectovaginal and complicated anal-perineal fistulas has been associated with high rates of complications and failure of repair. METHODS: This paper reports on 107 patients treated during the past 10 years by endorectal advancement flap repair. Ninety-two percent of the patients were women with mean age of 38 years (range, 20 to 71 years). Seventy-one had low rectovaginal, 28 had anterior anal-perineal, and 8 had posterior anal-perineal fistulas. The causes were obstetric injury, 48; cryptoglandular abscess-fistula, 31; Crohn's disease, 24; and trauma or after operation, 4. The technique completely preserves the sphincter muscle, covers the internal opening of the fistula tract with healthy rectal wall, and provides counter drainage to aid healing. RESULTS: No deaths occurred in the series. Persistent or recurrent fistula occurred in 17 patients (16%). Nine patients whose initial operation failed underwent a secondary successful operation. Continence status was unchanged in 80%, improved in 18%, and was unknown in two patients who still had intestinal flow diversion. Recurrence of the fistula did not result in destruction of the sphincter mechanism in those patients who underwent simultaneous reconstructive operation. CONCLUSIONS: The endorectal advancement flap repair successfully treated 93% of the complicated anorectal fistulas, avoiding fecal diversion and improving, not injuring, sphincter function. PMID- 8211683 TI - Aortic diameter as a function of age, gender, and body surface area. AB - BACKGROUND: An aortic aneurysm is defined as a 50% or greater increase in diameter compared with normal levels or the level of the left renal vein. However, normal diameters for many aortic segments are not known, and the aortic segment at the left renal vein may be enlarged. The purpose of this study was to determine normal diameters of the thoracic and abdominal aortas in relationship to age, gender, and body size. METHODS: Aortic diameters (ADs) were determined at four anatomic levels: thoracic aorta, abdominal aorta at the celiac axis, renal arteries, and midway between the renal arteries and the bifurcation. ADs were determined with the use of a video analyzer and an electronic caliper. Computed tomographic scans (n = 389) obtained for nonvascular diagnoses were analyzed according to gender, age, height, weight, and body surface area (BSA). RESULTS: At all levels and in each decade the AD is significantly greater in men than in women (p < 0.0001). BSA is a better predictor of size than height or weight. AD increased with age at all levels, and there was a positive correlation between the AD and BSA and gender. Expected ADs for each aortic segment may be calculated according to regression equations. Age-, gender-, and BSA-matched patients with abdominal aortic aneurysms revealed significant enlargements in all proximal aortic segments. CONCLUSIONS: AD at a given level is a function of gender, age, and BSA. When these variables are known, it is possible to calculate an expected AD. The AD is greater at all levels in patients with abdominal aortic aneurysms and in men compared with women. PMID- 8211684 TI - Lymphocyte dysfunction in injured adults with elevated Candida antigen titers. AB - BACKGROUND: Lymphocytes play an important role in the activation of polymorphonuclear neutrophil (PMN) antimicrobial functions. This study was undertaken to evaluate the ability of lymphocytes from severely injured adults with elevated Candida antigen titers to activate the anticandidal function of normal PMNs. METHODS: Lymphocytes from 13 injured adults with elevated Candida antigen titers (titer+) were isolated and incubated with or without heat-killed C. albicans. After a 48-hour incubation, cell culture supernatants were harvested and tested for the ability to activate the anticandidal function of normal PMNs. Lymphocytes from 13 volunteers and 13 injury-matched patients with negative Candida antigen titers (titer-) were studied for comparison. RESULTS: The patients with titer+ and titer- were well matched in terms of age, sex, Injury Severity Score, units of blood transfused, and length-breadth of antibiotic therapy. Patients with titer+ had a higher incidence of bacterial infections than did patients with titer-. Only 2 of the 13 patients with titer+ had a positive Candida culture. Lymphocytes from the volunteers and patients with titer- released large amounts of a PMN-activating factor(s) when exposed to C. albicans. Lymphocytes from the patients with titer+ were defective in their ability to release this activating factor(s) after exposure to C. albicans. CONCLUSIONS: Although culture evidence of Candida was uncommon, injured adults with elevated Candida antigen titers have lymphocyte dysfunction and often suffer documented bacterial infections. PMID- 8211685 TI - Long-term results of liver transplantation for biliary atresia. AB - BACKGROUND: Biliary atresia can be treated by portoenterostomy, which is primarily palliative, or by liver transplantation, which is primarily curative. The purpose of this study was to determine the long-term outcome of liver transplantation for the treatment of biliary atresia. METHODS: During an 8-year period, 45 patients who underwent liver transplantation for biliary atresia and 10 patients who were referred to our center for portoenterostomy were retrospectively analyzed. RESULTS: No patient with biliary atresia died awaiting liver transplantation. The waiting time for all patients was 36.7 +/- 42.8 days. Thirty-four patients (75.6%) required one transplant, whereas 11 patients (24.4%) required 17 retransplants. Twenty-two patients (48.9%) required 39 reoperations (1.8 per patient). There were 4.9 infectious episodes, 2.2 rejection episodes, and 4.4 readmissions per patient. However, 91% of reoperations, 80% of infections, and 78% of rejections occurred within 6 months of transplantation. The overall 7-year actuarial patient and graft survival for patients with biliary atresia was 86.2% and 62.7%, respectively. CONCLUSIONS: Our results indicate that long-term patient survival after liver transplantation for biliary atresia is excellent. However, portoenterostomy continues to have an initial complementary but limited long-term role in the treatment of infants with biliary atresia. PMID- 8211686 TI - Transjugular intrahepatic portosystemic shunt in the management of variceal bleeding: indications and clinical results. AB - BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) has proved to be a successful bridge to liver transplantation in the management of variceal bleeding. The safety and ease of this technique has now challenged standard surgical approaches to portal hypertension. To define the role of TIPS, we prospectively studied patients undergoing this procedure for variceal bleeding and/or ascites. METHODS: From September 1991 to September 1992, 45 patients entered a protocol that included assessment of liver chemistries, ammonia levels, coagulation profiles, liver synthetic function by caffeine-antipyrine clearance, ultrasonographic evaluation of hepatic and portal veins, portogram and direct measurement of portal vein pressures, upper endoscopy, computed tomography for liver volume and ascites, and formal neuropsychiatric evaluation. These studies were repeated at 3-month intervals or more frequently if bleeding or complications occurred. RESULTS: Technical success and control of bleeding were achieved in all patients with only three (7%) variceal rebleeds from recurrent portal hypertension. Complete and permanent control of clinical ascites was noted in all patients with this complication. Five of six deaths occurred from sepsis and multiorgan failure in intensive care unit-bound patients with Child class C liver disease. No serial changes were noted in liver chemistries; however, progressive loss of liver volume and prolongation of caffeine-antipyrine clearance was observed in most patients. In addition, hepatic vein stricture or shunt stenosis seen in nine patients (20%) required TIPS revision, whereas the frequent appearance of symptomatic encephalopathy was a main indication for transplantation in 11 of 14 patients. CONCLUSIONS: TIPS successfully controls variceal bleeding and may serve as a novel approach to control of diuretic resistant ascites. The uncertain long-term patency and progressive decline in synthetic function emphasize the importance of initiating proper trials comparing TIPS with other management strategies before indiscriminant use of this technique is seen. PMID- 8211687 TI - Determination of malignancy of thyroid nodules with positron emission tomography. AB - BACKGROUND: Current noninvasive evaluation techniques of thyroid nodules are nonspecific. We studied the use of a new noninvasive imaging modality, positron emission tomography (PET), in the evaluation of thyroid nodules. METHODS: Nineteen patients were studied before operation with PET with [18F]-2-deoxy-2 fluoro-D-glucose (FDG). Twelve patients had solitary thyroid nodules and seven had multinodular goiters. Fourteen overlapping transverse slices were acquired through the thyroid gland. A region of interest was drawn around the abnormal area and the maximum pixel value was calculated and corrected to produce a normalized value for FDG uptake. RESULTS: Four of the 12 nodules were malignant (three papillary and one follicular carcinoma), with the others being follicular adenomas. All of the multinodular goiters were benign. All of the malignancies had an FDG greater than 8.5 and all of the benign nodules had an FDG less than 7.6. The dose uptake ratio of FDG was 10.8 +/- 3.2 (mean +/- SD) for the malignancies and was significantly greater than the dose uptake ratio of either the follicular adenomas (4.3 +/- 2.0) or the dominant nodule in multinodular goiters (3.0 +/- 2.0). CONCLUSIONS: The FDG uptake as measured by PET scanning successfully discriminated between all benign and malignant tumors. This technique appears useful in the evaluation of thyroid nodules. PMID- 8211688 TI - Two hundred consecutive simultaneous pancreas-kidney transplants with bladder drainage. AB - BACKGROUND: Since 1982, 288 pancreas transplantations have been performed at the University of Wisconsin. This report reviews our experience with 200 consecutive simultaneous pancreas-kidney (SPK) transplantations during a 7-year period. METHODS: Two hundred consecutive SPK transplantations were performed between December 1985 to October 1992. Immediate posttransplant function and surgical and infectious complications were evaluated. Frequency of rejection episodes were analyzed, as was 5-year patient and graft survival. RESULTS: All but four pancreas transplants functioned immediately after transplantation. Three pancreas transplants failed because of thrombosis and one from primary nonfunction. Five year patient survival was 90.2%, kidney survival 80.3%, and pancreas survival 78.6%. There were 54 surgical complications. Fifteen patients have died since 1985. The most frequent cause of death was infection (three patients). A total of 678 infectious episodes were recorded. Urinary tract infection (n = 344) was the most frequent type of infection. Enteric conversion was necessary in 35 patients, with the most frequent indication being a leak of the duodenal segment. CONCLUSIONS: We concluded from this series that SPK transplantation is associated with higher cost and morbidity as compared with kidney transplantation alone. However, excellent long-term survival in combination with the clearly demonstrated benefits for secondary diabetic complications indicate that SPK transplantation is the procedure of choice for carefully selected patients with diabetes. PMID- 8211689 TI - Intraoperative localization of neuroendocrine tumors with 125I-TYR(3)-octreotide and a hand-held gamma-detecting probe. AB - BACKGROUND: This study evaluates a novel method of intraoperative localization of endocrine gastroenteropancreatic tumors with a hand-held gamma-detecting probe to detect in situ tumor binding of the radioiodinated somatostatin analog 125I TYR(3)-octreotide. METHODS: Seven patients with biochemical and radiologic evidence of a specific endocrine tumor, one patient with biochemical evidence of gastrinoma but no tumor localized by conventional imaging techniques, and four patients with equivocal preoperative biochemical or radiologic study results but suspected of harboring a neuroendocrine tumor underwent abdominal exploration with intraoperative injection of 125I-TYR(3)-octreotide. 298 +/- 63 microCi. A hand-held gamma-detecting probe was used during operation to determine whether gross tumor accumulated the radiolabeled analog and occult tumor could be detected. Positive uptake was defined as tumor/background ratios exceeding 2:1. RESULTS: The tumor in all seven patients with gross disease accumulated 125I TYR(3)-octreotide. Occult tumor beyond that appreciated with preoperative imaging or by routine operative exploration was detected in a patient with carcinoid tumor. In the patient with the occult gastrinoma the probe detected the lesion within the duodenal bulb before duodenotomy and also predicted what proved histologically to be positive peripancreatic adenopathy. There was a single false positive reading from the stomach in a patient with suspected carcinoid tumor in whom no tumor could be found grossly or histologically. A pancreatic mass that probed negative proved to be an adenocarcinoma of ductal origin. CONCLUSIONS: Tumor-specific peptide-receptor binding can be detected in situ with 125J-TYR(3) octreotide and a hand-held gamma-detecting probe. This technique may facilitate neuroendocrine tumor localization and operative cytoreduction. PMID- 8211690 TI - Cigarette smoking and peripheral arterial occlusive disease. AB - BACKGROUND: The importance of cigarette smoking in the etiology of peripheral arterial occlusive disease is well known, but there have been few studies that have quantified this relationship. METHODS: A case-control study design was used in which the case subjects were men with a history of claudication for at least 1 year and abnormal findings on noninvasive blood flow studies or on arteriography; control subjects were men attending the same hospital for conditions other than cancer, with no history of cancer or vascular disease and with a normal ankle brachial index. Case and control subjects were interviewed by a trained nurse interviewer using a pilot-tested questionnaire. Current smoking status was confirmed by serum cotinine level estimation. Univariate odds ratios for smoking and other potential risk factors were calculated, and their significance was tested by comparison with the chi-squared distribution. Logistic regression analysis was used to adjust the effect of smoking for confounding variables, and the regression equation was used to estimate the proportion of disease attributable to smoking. RESULTS: Of the patients approached, 94% of the eligible case subjects and 93% of the eligible control subjects agreed to participate. Recruitment ended with 102 cases of peripheral arterial occlusive disease and 99 controls. Most of the control subjects were attending clinics for other surgical specialties. Compared with men who had never smoked the relative risk was 7 for exsmokers and 16 for current smokers (p < 0.001). The relative risk increased directly with the lifetime number of cigarettes smoked, the chi-squared test for trend being highly significant (p < 0.001). Age, lipoprotein concentration, body mass index, and history of hypertension or heart disease were also significant risk factors. CONCLUSIONS: After adjustment for confounding variables the estimate of the fraction of disease attributable to smoking was 76%. PMID- 8211691 TI - Comparison of mutations of ras oncogene in human pancreatic exocrine and endocrine tumors. AB - BACKGROUND: Ras oncogene mutations have been found in many human cancers; however, pancreatic endocrine tumors have rarely been studied. The purpose of this study was to analyze ras mutations in pancreatic endocrine tumors and to compare these results with the incidence of ras mutations in pancreatic exocrine cancers studied in our laboratory. METHODS: Ras oncogene mutations were studied in 33 foregut endocrine tumors (pancreatic 31, duodenal submucosa 2). Eleven were insulinomas, 12 gastrinomas, 2 glucagonomas, and 11 others were nonfunctioning islet cell carcinomas. Thirteen were benign and 20 were malignant. These were compared with 65 pancreatic exocrine cancers. Tumors were microdissected from paraffin-embedded sections. DNA was extracted and amplified by polymerase chain reaction. Mutations were detected by a oligonucleotide hybridization method with sequence-specific phosphorus 32-radiolabeled probes. RESULTS: No ras mutations were identified among the 33 pancreatic endocrine tumors. In contrast, 51 of 65 (78.5%) pancreatic exocrine cancers exhibited a ras mutation. Fifty were K-ras mutations and one unusual tumor exhibited a N-61 ras mutation. CONCLUSIONS: Ras oncogene mutations do not play a role in the tumorigenesis of pancreatic endocrine tumors. PMID- 8211692 TI - Laparoscopic herniorrhaphy: results and technical aspects in 450 consecutive procedures. AB - BACKGROUND: The effectiveness of laparoscopic herniorrhaphy, the patient outcome, and technical aspects have been controversial. We have performed 450 consecutive laparoscopic inguinal herniorrhaphies and have reviewed the rationale, technical aspects, and the outcomes. METHODS: Four hundred and fifty consecutive laparoscopic herniorrhaphies were performed using synthetic mesh for tensionless repair and adhering to surgical principles of preperitoneal herniorrhaphy. Patients were 16 to 83 years of age, 74% men, 26% women. Mesh was transfixed to anatomic landmarks with suture or staples. The peritoneum was closed, separating mesh from abdominal contents. RESULTS: Ninety percent of patients were discharged from perioperative care; 10% were in the hospital 23 hours as a result of urinary retention, cardiac disease, etc. No adhesive or mesh complications occurred. Three hernias recurred at 2 to 4 months after operation. Two were repaired laparoscopically. CONCLUSIONS: Laparoscopic inguinal herniorrhaphy is a safe and effective procedure. It compares favorably with other classic methods of hernia repair (especially use of a tensionless repair with mesh). Patients exhibit minimum morbidity and ambulate soon with minimal discomfort. This repair should be considered preferential in many subsets of patients. PMID- 8211693 TI - Organization and development of a university multidisciplinary wound care clinic. AB - BACKGROUND: A multidisciplinary wound care clinic was established to diagnose and treat patients with nonhealing ulcers of the lower extremity. METHODS: The clinic was organized under the direction of the departments of vascular surgery and dermatology with support by the departments of plastic surgery, hyperbaric medicine, orthopedic surgery, and podiatry, and a research nurse. RESULTS: In the first 4 years and 3 months, 683 patients were evaluated. One hundred seventy-one patients underwent outpatient testing in the noninvasive vascular laboratory and 30 patients underwent angiography. Causes of the ulcers were venous stasis, 280 patients (41%); diabetic neuropathy, 182 patients (27%); arterial insufficiency, 119 patients (17%); rheumatologic disorders, 38 patients (6%); trauma, 15 patients (2%); and in 49 patients (7%) a variety of other disorders. One hundred seventy-nine operations were performed including 86 operating room debridements, 48 amputations (43 toe, 4 below knee, 1 above knee), 23 arterial bypasses, 1 venous bypass, 14 skin grafts, 2 pedicle flaps, and 5 excisions of tumor. Fifty six patients with cellulitis were admitted to the hospital for intravenous antibiotics and 12 patients were treated with hyperbaric oxygen therapy. One hundred thirty-two patients were entered into randomized prospective trials of topical growth factors on Institutional Review Board approved protocols. CONCLUSIONS: We concluded that a multidisciplinary approach to wound care is beneficial to patients with chronic wounds and provides a mechanism for clinical investigation on the healing of problem wounds. PMID- 8211694 TI - Value of physiologic assessment of foregut symptoms in a surgical practice. AB - BACKGROUND: The aim of this study was to evaluate the reliability of symptoms in the diagnosis of gastroesophageal reflux disease and esophageal motility disorders as assessed by functional tests. METHODS: In 365 patients referred for suspected esophageal functional disease, symptomatic assessment was compared with the results of esophageal manometry and ambulatory 24-hour pH monitoring of the distal esophagus. RESULTS: Based on the patients' chief complaint, the symptomatic diagnosis was gastroesophageal reflux (44%), esophageal motor disorder (26%), chest pain of esophageal origin (9%), reflux and aspiration (8%), and abdominal pathology (12%). The symptomatic diagnosis was considerably altered by the results of the esophageal function tests: gastroesophageal reflux and motility disorders were found in all symptomatic diagnostic groups and a large number of patients in each group tested normal. The sensitivity and specificity of symptom-based diagnoses for functional disease were low. CONCLUSIONS: The results of this study showed that symptoms are an unreliable guide of esophageal abnormality, illustrating the need for objective testing in these patients, particularly to avoid inappropriate medical or surgical therapy. PMID- 8211695 TI - Right ventricular response after myocardial contusion and hemorrhagic shock. AB - BACKGROUND: Prior functional studies on myocardial contusion (MC) have emphasized left ventricular performance even though the right ventricle (RV) is more likely to be injured after blunt trauma. Furthermore, associated injuries requiring resuscitation and surgery are frequently present. Our aim was to evaluate the impact of MC on RV function after MC and subsequent resuscitation from hemorrhagic shock. METHODS: RV performance was evaluated with a modified pulmonary artery catheter that determines RV volumes and ejection fraction (RVEF), as well as filling pressures and cardiac output in an anesthetized swine model. RESULTS: MC caused a 28% fall in mean arterial pressure and a 33% decrease in cardiac output. RVEF was 82%, and RV stroke work was 49% of baseline after injury. Resuscitation of hemorrhagic shock to baseline preload or greater failed to restore mean arterial pressure or cardiac output (depressed 23% and 22%, respectively). RV end-diastolic volume returned to baseline and central venous pressure was increased. RV dysfunction was depicted by a sustained depression of RV stroke work and RVEF. CONCLUSIONS: Impaired RV compliance and contractility, which was evident throughout this study, may hamper resuscitative efforts after multiple blunt trauma. RV monitoring may be useful in this setting. PMID- 8211696 TI - Early experience with homograft aortic root replacement for complex aortic pathology. AB - BACKGROUND: Complex aortic valve and root pathology presents a serious operative challenge. METHODS: During the last 45 months 21 cryopreserved homograft root replacements have been performed in 19 patients. The ages of the patients ranged from 28 to 77 years; there were 15 men and four women. Six patients had endocarditis, four prosthetic and two native valve endocarditis. One patient underwent homograft aortic root replacement twice; one underwent concomitant homograft right ventricular outflow tract reconstruction for pulmonic endocarditis. Causes of aortic pathology in the other 13 patients included ascending aortic aneurysm with valvular regurgitation in seven, Marfan syndrome in two, and four aortic dissections with aortic regurgitation. Ten of the nineteen patients were undergoing reoperative procedures. RESULTS: There were three hospital deaths and one death at home of unknown cause. Two of the three patients who died in hospital had undergone redo cardiac procedures. Dramatic functional class improvement was seen in all survivors. CONCLUSIONS: Follow-up from 2 to 45 months in the fifteen survivors revealed no clinical or significant echocardiographic evidence of valvular regurgitation or recurrent infection. We believe homograft root replacement provides an excellent method of reconstruction with several advantages unique to human valved conduits, including ease of handling, lack of synthetic nidus for recurrent infection, and absence of thrombogenic materials. Homografts should be considered the approach of choice in complex valvular and root infectious processes. PMID- 8211697 TI - Synchronous, metachronous, and multiple hepatic resections of liver tumors originating from primary gastric tumors. AB - BACKGROUND: The role of hepatic resection for noncolorectal gastrointestinal malignancies involving the liver is not well defined. To address this issue we studied our experience with resection of liver tumors arising from primary gastric malignancies. METHODS: A retrospective study of 195 patients who underwent a total of 207 liver resections identified 12 patients with primary gastric cancer who underwent 16 resections for liver involvement. There were 10 adenocarcinomas and two leiomyosarcomas. We examined the type of hepatic surgery, the status of residual disease, and the primary histologic findings. Morbidity, mortality, and actual survival rates were recorded. RESULTS: Thirty-day operative mortality was 8.3% (1 of 12). Hospital mortality was 25% (3 of 12). Operative morbidity occurred in three of nine survivors (33%). Synchronous en bloc resection (n = 3) of stomach and liver for adenocarcinoma produced two long-term survivors (no evidence of disease for 10 and 13 years). Mean survival after synchronous discontinuous resection (n = 4) was 8 months (range, 2 to 17 months). Metachronous resection for adenocarcinoma (n = 3) produced one long-term survivor (74 months), and one patient with recurrent leiomyosarcoma underwent a total of five liver resections and survived 64 months. CONCLUSIONS: For adenocarcinoma, en bloc resection of contiguous liver involvement produced long-term survivors. Synchronous resection of discontinuous metastases did not. Metachronous resection of isolated disease and multiple resections of recurrent isolated disease may have value in carefully selected patients. PMID- 8211698 TI - Use of endoscopic retrograde cholangiopancreatography in the management of biliary complications after laparoscopic cholecystectomy. AB - BACKGROUND: Current options in the management of bile duct injuries caused by laparoscopic cholecystectomy include diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) and open laparotomy with direct repair. The goal of this review was to clarify the role and evaluate the potential of endoscopic techniques to diagnose and treat bile duct injuries. METHODS: The records of all patients undergoing biliary tract surgery at our hospitals for the period from December 1989 to February 1993 were reviewed. Twenty-five patients were identified with bile duct injuries during laparoscopic cholecystectomy. RESULTS: ERCP was performed for diagnostic or therapeutic purposes in 22 of the 25 patients; successful opacification of the biliary tree was achieved in 21 (95%) of the 22 patients. In these 21 patients the location and nature of the injury were identified correctly in 19 (90%). In six of the 25 cases, interventional ERCP was used as the primary treatment of these injuries. Successful treatment was achieved in five (83%) of the six cases, although laparotomy was required in two to drain the abscess cavity better. Open surgical repair was performed as the primary treatment in the remaining 19 patients. Interventional ERCP with stenting was required in six and transhepatic stenting in one of these patients as an adjunctive treatment for stricture or persistent fistula. Six (86%) of these seven patients have been treated successfully to date in this manner. CONCLUSIONS: ERCP is a uniquely helpful diagnostic and therapeutic technique in the management of laparoscopic biliary complications. Open surgical repair remains the procedure of choice for patients with loss of bile duct tissue or long complex strictures. ERCP with sphincterotomy, balloon dilatation, and stenting is an accepted alternative approach for bile leaks (fistulas) and treatment of shorter strictures resulting from either the initial laparoscopic injury or the initial repair. PMID- 8211699 TI - Postoperative pneumonia: a prospective study of risk factors and morbidity. AB - BACKGROUND: Postoperative pneumonia (PP) is a major complication that has been linked to microaspiration of pathogens originating in the gastrointestinal tract. This prospective study was performed to define the role of gastric bacterial aspiration in the development of PP. METHODS: Informed consent was obtained before operations from 140 veterans scheduled for major elective procedures requiring nasogastric tubes, and cultures were obtained of the gastric contents and sputum twice daily after operation. RESULTS: PP developed in 26 (18.6%) of 140 patients. The patients who had PP did not differ from those with no pneumonia after operation except for a history of chronic obstructive pulmonary disease, which was found in 38.5% of those with PP compared with 20% of patients with no pneumonia (p < 0.05). Morbidity was increased in association with PP, because length of stay in the surgical intensive care unit (6.2 vs 2.6 days), days intubated (2.7 vs 0.6), total postoperative days (15.3 vs 8.4), and mortality rates (19.2% vs 1.7%) were greater than in patients with no pneumonia. Gastric pathogens were present on entry in 38% of patients, and 32% of these had PP compared with 13% whose initial gastric cultures were sterile (p = 0.01). Colonization of sputum for greater than 24 hours with gastric pathogens occurred in 28% of patients. These patients had a 40% incidence of PP compared with 12% in patients without such evidence of microaspiration (p < 0.01). CONCLUSIONS: PP is a morbid postoperative complication associated with not only chronic obstructive pulmonary disease but also the presence of gastric bacteria during operation and transmission of gastric bacteria to the pulmonary tree after operation. PMID- 8211700 TI - Delivery room repair of gastroschisis. AB - BACKGROUND: Outcome for most abdominal wall defects is related to the presence or absence of additional anomalies or prematurity. In gastroschisis, outcome is almost as closely related to the severity of the inflammatory "peel" on bowel that is thought to result from direct contact with amniotic fluid. Improving eviscerated bowel quality would be expected to reduce morbidity in these patients. METHODS: From 1986 to 1991, 32 patients with the antenatal diagnosis of gastroschisis were treated. All were delivered by cesarean section; 13 surgical repairs were made immediately in the delivery room. Surgical repairs in 19 patients were made at less than 6 hours of age after transfer from the delivering hospital to the pediatric surgery center. RESULTS: Thirty percent of infants who underwent surgical repair in delivery room and 32% of infants who underwent urgent surgical repair were either premature or had significant associated anomalies. Seventy-three percent of delivery room repair group had fascial repairs compared with 37% in the transferred group. When infants more than 34 weeks' gestation without associated anomalies are compared with transferred infants, delivery room repair group underwent more frequent fascial repair (8 of 9 vs 5 of 13, p < 0.03), were extubated sooner (2.9 vs 7.4 days, p < 0.04), tolerated enteral feedings earlier (8.1 vs 22.2 days, p < 0.009), and required fewer hospital days (13.6 vs 31.3 days, p < 0.01). Eviscerated bowel of infants who underwent immediate surgical repair lacked the characteristic matted, edematous, and fibrinous coated appearance seen in transferred patients. CONCLUSIONS: Immediate delivery room repair of gastroschisis results in increased fascial repairs and earlier extubation, feeding, and hospital discharge. These benefits appear to be due to the minimal reactive peel on eviscerated bowel at birth. PMID- 8211701 TI - The pull-through procedure: technical factors in influencing outcome, with emphasis on pouchitis. AB - BACKGROUND: The purpose of the study was to review those features that we believed to be critical to the successful performance of the ileal pouch-anal anastomosis, or pull-through, procedure, and specifically the complication of pouchitis. METHODS: The charts of 205 patients who successfully underwent ileal pouch-anal anastomosis procedure were reviewed. No follow-up was available in five patients; therefore, the basis of this report and its analysis was based on 200 consecutive procedures in which at least two of the three surgeons participated. Particular emphasis was placed on continence, particularly nighttime continence. The incidence of pouchitis, either a single episode or intermittent episodes, was surveyed. Particular attention was paid to the level of rectal mucosectomy and anastomosis at the top of the columns of Morgagni, thus retaining the transitional zone. RESULTS: Only 5% of patients were incontinent in the absence of pouchitis. Twenty-five patients (13%) wore a pad at night, but only nine (5%) wore a pad during the day. Of those patients with pouchitis, 6% (12) have had a single episode and 12% (23) were intermittently on medication. Therapy of pouchitis was usually carried out with ciprofloxacin 500 mg by mouth everyday or twice a day. CONCLUSIONS: Ileal pouch-anal anastomosis is an excellent procedure, provided technical details are adhered to. Satisfactory outcome with respect to nighttime continence can be achieved with rectal mucosectomy with minimal manipulation and retaining the transitional epithelium, performing the pouch anastomosis at the top of the columns of Morgagni. The incidence of pouchitis is disappointing but need not be inhibiting of either patients or carrying out this life-saving procedure in patients with ulcerative colitis and familial polyposis. PMID- 8211702 TI - Breast biopsy with needle localization: accuracy of specimen x-ray and management of missed lesions. AB - BACKGROUND: One of the more frustrating complications after breast biopsy with needle localization is a missed lesion. To reduce the number of missed lesions, radiographs of the surgical specimen are usually obtained. In this study we determined the accuracy of specimen x-ray, the incidence of missed lesions, and the management of patients with this complication. METHODS: The result of specimen x-ray was compared with that of a postoperative mammogram in 192 patients who underwent breast biopsy with needle localization. The incidence of missed lesions was also determined from postoperative mammogram, and the management of patients with this complication was analyzed. RESULTS: The incidence of false-positive specimen x-ray was 7.8% and that of false-negative 55%. The sensitivity, specificity, and accuracy of specimen x-ray were 96%, 28%, and 89%, respectively. The incidence of missed lesions was 3.2% and of incompletely excised lesions 6.4%. Eighteen of 24 patients with a missed or incompletely excised lesion were treated expectantly because postoperative mammogram showed the lesion to be stable. None of these patients has required a subsequent biopsy. CONCLUSIONS: Specimen x-ray can be false positive or false negative. An important implication of this finding is that a postoperative mammography should always be performed after biopsy with needle localization, regardless of the result of the specimen x-ray, to make certain the lesion has not been missed. PMID- 8211703 TI - Effect of failed computed tomography-guided and endoscopic drainage on pancreatic pseudocyst management. AB - BACKGROUND: Computed tomography and endoscopic drainage are used increasingly to treat pancreatic pseudocysts (PP). We reviewed our experience with PP to compare the outcomes of patients operated on initially (group 1) with those whose nonoperative treatment failed (computed tomography-guided or endoscopic drainage) before operation (group 2). METHODS: The records of 70 consecutive patients operated on for PP were reviewed. The 52 patients (74%) in group 1 and 18 (26%) in group 2 were compared in terms of clinical features, laboratory test results on examination and before operation, operative findings, morbidity, mortality, and recurrence rates. RESULTS: Before the initial drainage attempt, mean serum amylase level was higher in group 2 (542 +/- 25 vs 163 +/- 17 IU/L; p = 0.01). All other laboratory values were similar. Before operative drainage, group 2 patients had lower hemoglobin (10.7 +/- 0.5 vs 12.2 +/- 0.3 gm/dl; p < 0.05) and serum albumin level (2.7 +/- 0.2 vs 3.5 +/- 0.1 mg/dl; p < 0.01) than group 1. Morbidity was twice as frequent in group 2 (33% vs 14%). The time from initial attempt at drainage to PP resolution was longer in group 2 (104 +/- 36 vs 20 +/- 4 days; p = 0.01). However, the time from operation to resolution was similar in both groups (21 +/- 8 vs 20 +/- 4 days). CONCLUSIONS: Failed nonoperative drainage is associated with a protracted illness and carries a risk of increased morbidity after operative intervention. PMID- 8211704 TI - Radiation therapy as definitive treatment for selected invasive rectal cancer. AB - BACKGROUND: Eighty-four patients with invasive rectal adenocarcinoma were definitively treated with radiation during a period of 9 years in an attempt to achieve "local control" (eradication of rectal cancer and its associated morbidity) without radical resective surgery. METHODS: Initially, endocavitary radiation alone was used in 13 patients with "ideal" carcinomas and in six patients with aggressive cancers. To improve local control, 4500 cGy external radiation before the 6000 cGy endocavitary radiation was used to treat 28 ideal lesions, 15 "nonideal" but potentially curable cancers, 14 aggressive cancers, and 8 patients with incurable metastatic disease. RESULTS: Endocavitary radiation alone resulted in local control for 8 of 13 patients with ideal carcinomas (62%); eventually 11 of 13 (85%) had control after three successful salvage abdominoperineal resections. Local control was accomplished in none of six patients with aggressive cancers. Use of external radiation before endocavitary radiation achieved local control in 93% of patients with ideal lesions, eventually 100% after two salvage abdominoperineal resections. Of the 15 nonideal but potentially curable lesions, 100% had eradication of local disease with the combined modalities. Of the 14 with aggressive cancers and 8 with metastatic disease, 19 suffered failure of local control (86%). Eight of these had local salvage by surgical resection; the others died with local failure within 6 months. CONCLUSIONS: External radiation, combined with endocavitary radiation, is excellent, definitive treatment for selected, favorable, invasive rectal cancers; however, there is little place for nonresective management of aggressive rectal cancer, even for palliation, unless life expectancy is less than 6 months. PMID- 8211705 TI - Cholelithiasis in pancreas and kidney transplant recipients with diabetes. AB - BACKGROUND: Vascularized pancreas transplantation (PTx) for type I diabetes mellitus results in euglycemia at the expense of chronic immunosuppression, hyperinsulinemia, and dyslipidemia. However, the effect of PTx on native biliary lithogenesis remains unknown. METHODS: To address this issue, we retrospectively studied 72 consecutive pancreas transplant recipients and compared them with patients both with (n = 35) and without (n = 52) diabetes mellitus undergoing kidney transplantation alone (KTA). All patients underwent pretransplantation abdominal ultrasonography, which was repeated at 6- to 12-month intervals after transplantation. PTx recipients were managed with quadruple immunosuppression with OKT3 induction. Kidney transplant recipients received cyclosporine and prednisone. RESULTS: Seventeen (30.4%) of 56 evaluable PTx recipients had gallstones at a mean interval of 13 months (range, 5 to 24) after PTx. Eleven patients underwent open cholecystectomy (with one surgical exploration of common bile duct for choledocholithiasis), three underwent laparoscopic cholecystectomy, and the other three are being managed expectantly. Gallstone analysis revealed predominantly cholesterol stones. The incidence of cholelithiasis in kidney transplant recipients with and without diabetes mellitus was 27.3% and 12.2%, respectively (p = 0.04). CONCLUSIONS: Pancreas transplant and kidney transplant recipients with diabetes are predisposed to the development of gallstones compared with recipients without diabetes. An interaction between diabetes mellitus-induced gallbladder dysmotility and cyclosporine-induced cholestasis may be a possible mechanism. We recommend serial ultrasonographic examinations in pancreas transplant and kidney transplant recipients, and cholecystectomy in pancreas transplant recipients with cholelithiasis should be considered. PMID- 8211706 TI - Localization of 5-HT1A receptors to astroglial cells in adult rats: implications for neuronal-glial interactions and psychoactive drug mechanism of action. AB - Although tissue culture studies have shown a variety of neurotransmitter receptors on astroglial cells, verifying these observations in adult animals has been difficult and rarely accomplished. In the current study we have used double immunocytochemistry to localize 5-HT1a receptors to astroglial cells in fixed sections of adult rat brain. The astroglial cells were identified using an antibody raised against the astroglial-specific protein glial fibrillary acidic protein (GFAP). To label the 5-HT1a receptor, we used an antibody we recently raised against a unique peptide sequence occurring in the second extracellular loop of the receptor. Our results show that the 5-HT1a receptor occurs in relatively high abundance on astroglial cells. There is regional specificity, the receptor being much more commonly found in septum and hippocampus than striatum. There are also intraregional differences in that even within a single brain region one astrocyte may have very high levels of the receptor while an adjacent cell has none. We propose that the cellular localization of this receptor could have significance in understanding the mechanism of action of 5-HT1a receptor active drugs in alleviating anxiety and depression. The mechanism may be through the release of a neurotrophic agent, S-100 beta, from astrocytes. This factor may then cause regeneration or sprouting of neuronal terminals which have been lost due to a disease process. PMID- 8211707 TI - Spontaneous activity and recurrent inhibition in cultured hippocampal networks. AB - As a model for an integrated neuronal network based on the concept of modular units, we have investigated the occurrence of spontaneous activity and the formation of synaptic circuits in primary cultures of dissociated hippocampal neurons from the embryonic rat. Sodium-dependent action potentials (APs) could be elicited after 1 day in vitro (DIV), whereas spontaneous postsynaptic potentials (PSPs), "miniature" PSPs and APs appeared after 3-6 DIV. The number of cells with spontaneous APs and the rate of APs increased during development of the neuritic network. In addition to a stochastic spike interval distribution, pyramid-shaped neurons could be identified after 10-12 DIV, which fired preferentially at interspike intervals between 20-120 ms and 190-400 ms. This distinctive bimodal interspike interval pattern was sensitive to GABA-A antagonists. Simultaneous recordings of pairs of neurons demonstrated recurrent inhibitory, GABA-ergic synaptic circuits. In addition, a subpopulation of GABAergic neurons could be visualized by immunocytochemistry. These results are discussed in relation to the hypothesis that spontaneous firing of connected neurons is network-driven, based on synaptic "noise" and patterned by recurrent inhibition. PMID- 8211708 TI - Long lasting changes in morphine-induced mesolimbic dopamine release after chronic morphine exposure. PMID- 8211709 TI - [Urinary tract infection--diapers control us. Interview by Kirsten Bjornsson]. PMID- 8211710 TI - [Urinary tract infection--so far an unknown risk]. PMID- 8211711 TI - [Urinary tract infection--continuously for many catheters]. PMID- 8211712 TI - [Urinary tract infection--late consequences and mortality]. PMID- 8211713 TI - [Urinary tract infection--know a little]. PMID- 8211714 TI - [Urinary tract infection--guided by infection]. PMID- 8211715 TI - [Education--the genuine article]. PMID- 8211716 TI - [Education--education close to reality]. PMID- 8211717 TI - [Urinary tract infection--a 10-year contribution]. PMID- 8211718 TI - [Urinary tract infection--painful, dangerous and expensive]. PMID- 8211719 TI - [Urinary tract infection--test your knowledge]. PMID- 8211720 TI - [Urinary tract infection--improved hygiene is necessary]. PMID- 8211721 TI - [Asylum seekers--they need kindness and mental fortitude. Interview by Tom Heinemann]. PMID- 8211722 TI - [Asylum seekers--not more than 9 months. Interview by Tom Heinemann]. PMID- 8211723 TI - [Ambulatory care. Support in difficult times]. PMID- 8211724 TI - [Health policy--save us from the incompetent. Interview by Mette Fjordbo]. PMID- 8211725 TI - [Health policy--prevention rarely pays. Interview by Mette Fjordbo]. PMID- 8211726 TI - [Care of the aged. The elderly in Japan. Interview by Anette Krarup]. PMID- 8211727 TI - [Health policy. People want to pay. Interview by Kirsten Bjornsson]. PMID- 8211728 TI - [Asylum seekers--a lot of mental stress]. PMID- 8211729 TI - [Hospice. Inger Nielsen. Interview by Mette Fjordbo]. PMID- 8211730 TI - [Hospice. Annelise og Erik]. PMID- 8211731 TI - [Taxation of pensions. So it goes with pensions]. PMID- 8211732 TI - [WHO--focus on accidents and violence]. PMID- 8211733 TI - [Organizational policy is also ethics and morals]. PMID- 8211735 TI - [Tax orientation. Nurses' income tax 1992]. PMID- 8211734 TI - [Work technology. Let the patient help you]. PMID- 8211736 TI - [Work arrangement]. PMID- 8211737 TI - [Parental leave--home with Christian]. PMID- 8211738 TI - [Executive Board]. PMID- 8211739 TI - [Negotiations 93--a clear "no"]. PMID- 8211740 TI - [Hospice--payment according to means. Interview by Mette Fjordbo]. PMID- 8211741 TI - [Health promotion--no interest. Interview by Kirsten Bjornsson]. PMID- 8211742 TI - [Health promotion--for doctors' fees. Interview by Kirsten Bjornsson]. PMID- 8211743 TI - [General practice--lacking recognition. Interview by Kirsten Bjornsson]. PMID- 8211744 TI - [Lacking involvement]. PMID- 8211745 TI - [Documentation: quality for patients on chemotherapy]. PMID- 8211746 TI - [Work environment. Lifting technique and bedside awards]. PMID- 8211748 TI - [Negotiations 93. A big task. Interview by Soren Palsbo]. PMID- 8211747 TI - [Negotiations 93. The clock to strike is ticking away]. PMID- 8211749 TI - [General practice. Nurse consultation]. PMID- 8211750 TI - [Symposium in nursing. As others see us]. PMID- 8211751 TI - [Symposium in nursing. The key to the medicine cabinet. Interview by Grethe Kjaergaard]. PMID- 8211752 TI - [Symposium in nursing. In the nurses' power]. PMID- 8211753 TI - [Drugs--greater demand on nurses]. PMID- 8211754 TI - [Management--nursing workload measurement and professional judgment]. PMID- 8211755 TI - [Malpractice--dismissal of charge of negligence]. PMID- 8211756 TI - [Malpractice--patient was her mother]. PMID- 8211757 TI - [Malpractice--nurses found innocent]. PMID- 8211758 TI - [Work environment]. PMID- 8211759 TI - [Consumer research--those friendly and capable home health nurses]. PMID- 8211760 TI - [Education--enthusiastic new health care]. PMID- 8211761 TI - [Hospital--shared management refused in West Zealand]. PMID- 8211762 TI - [Negotiations 93--conciliation officer at the bargaining table. Interview by Soren Palsbo]. PMID- 8211763 TI - [ICN--quality economics and nursing]. PMID- 8211764 TI - [Oncology--only meals are routine]. PMID- 8211765 TI - [Executive Board]. PMID- 8211766 TI - [Negotiations 93--the Executive Board negotiates indirectly]. PMID- 8211767 TI - [Research--hormones or not?]. PMID- 8211768 TI - [Yugoslavia--where war ravages. Interview by Charlotte Meldal]. PMID- 8211769 TI - Chartbook on health data on older Americans: United States, 1992. Health care use and its cost. PMID- 8211770 TI - Chartbook on health data on older Americans: United States, 1992. Health status. PMID- 8211771 TI - Chartbook on health data on older Americans: United States, 1992. Special topics. PMID- 8211772 TI - [The comparative evaluation of the efficacy of different therapeutic plans in acute nonlymphocytic leukemias]. AB - 78 previously untreated patients with acute non-lymphoblastic leukemia (ANLL) were assigned to cytosar-anthracyclines therapeutic programs: 29 (group I) received daunorubicin and AraC, 18 (group II) aclacinomycin A and AraC, 12 (group III) the scheme 3 + 7 with 12 mg/m2 novantron instead of daunorubicin, 19 (group IV) the scheme 3 + 7 with 12 mg/m2 idarubicin and cytosar. Groups I-III comprised both prognostically favorable and unfavorable ANLL variants, group 4 patients had for the most part unfavorable prognosis (MO-M3). A mean age of the patients was 41-42. Complete remissions were observed in 17 (58.6%), 9 (50%), 10 (83.3%), 11 (57.9%) patients of groups I, II, III and IV, respectively. An initial course of the treatment produced complete remissions in 65%, 33%, 80% and 90.9% of them, respectively. A mean duration of cytostatic leukothrombocytopenia was the longest in groups III and IV (16-22 days). Nonhematological toxicity occurred in the form of enteropathy and hepatitis. During the remission induction and consolidation 76% of the deaths were caused by infection and hemorrhagic diathesis. The median remission lasted 17.5, 13.5 and 5 months in groups I, II and III, respectively, and was not reached in group IV because of continuing remission in 50% of the patients by the end of the follow-up period (14 months). A 2-year survival rate was observed in 25% (group I), 11% (group II), 30% (group III) and 40% (group IV). PMID- 8211773 TI - [The prognostic factors in chronic myeloleukemia]. AB - Most informative, practicable clinical, morphological and histomorphological criteria have been identified characterizing the stage of clinical evolution of chronic myeloid leukemia (CML) by the time of its diagnosis. Such criteria can be utilized for featuring the risk of short- and long-term CML aggravation. The patients at risk of the disease acceleration are recognized, the survival for various risk groups is analyzed. By a complex of significant signs the patients may be diagnostically classified as being at standard, moderate and high risk. PMID- 8211774 TI - [The necessity for the combined use of the ultrasonic study of the abdominal cavity organs and of the histomorphometry of the bone marrow in chronic myeloleukemia]. AB - Forty-one patients with chronic myeloid leukemia (CML) were divided into 3 groups: 13 patients in a chronic phase prior to cytostatic treatment group 1; 17 patients in a chronic phase treated with myelosan group 2; 11 patients in a blast transformation phase group 3. All of them underwent abdominal sonography in line with marrow histomorphometry. Ultrasound investigation is thought indispensable in examination of CML patients as it registers negligible enlargement of the liver and spleen and provided their echo structure. It makes possible to trace stages of the tumor process development. CML involves in the pathological process the kidneys as shown by changes in the echo pattern, concrements are often formed in the pelvicalyceal system. Group 1 patients demonstrated reduced area of the bone tissue by morphometrical evaluation of the bone marrow. This means prevalence of osteolysis in CML onset. In group 3 patients this value is higher indicating osteosclerosis predominance. Comparison of the ultrasonic and histomorphometric data suggest that enlargement of the spleen and liver with diffuse vegetations of the connective tissue and their fibrotic lesion of the parenchyma correlated with the severity dissemination of hemopoietic tissue collagen fibrosis. It is evident that CML is characterized by fibrosis involving simultaneously bone marrow, splenic and hepatic parenchyma. PMID- 8211775 TI - [Critical states in hemoblastoses (their typical forms and survival in a resuscitation department)]. PMID- 8211776 TI - [The cytological and biochemical aspects of studying the cerebrospinal fluid in patients with chronic myeloleukemia]. AB - The investigation of cell composition and different biochemical parameters (ceruloplasmin, lactate dehydrogenase, aldolase, ferritin, beta-2-microglobulin) in cerebrospinal fluid has been performed in 37 patients with chronic myeloid leukemia at different clinicohematological stages. The age of the patients ranged from 16 to 67 years. CNS involvement has been diagnosed in 8 (21.6%) patients by clinical and cytological criteria and in 5 (13.5%) patients on the basis of changes in liquor cytograms and in biochemistry. Morphological substrate of leukemic infiltration may be represented by blast cells and cells of granulocytic line of all stages of differentiation. Direct correlation has been established between ferritin and beta-2-microglobulin levels in liquor and its cytological patterns. This permits a conclusion on possible usage of liquor concentration of beta-2-microglobulin and ferritin measurements as additional tests in the diagnosis of neuroleukemia in chronic myeloid leukemia. PMID- 8211777 TI - [The immunological phenotype and proliferative activity of the tumor lymphocytes in multiple myeloma]. AB - An immunological phenotype of blood lymphocytes and proliferative activity of tumor cells were studied using a panel of monoclonal antibodies to lymphocyte differential antigens and tracer 3H-thymidine, respectively, in 84 patients with multiple myeloma. CD-19 and CD38 antigens were identified as markers for circulating tumor lymphocytes. The count of CD38+ and CD71+lymphocytes correlated with the count of marrow plasmocytes including 3H-thymidine in the disease recurrence. Proliferative parameters of blood lymphocytes, plasmocytes and lymphocytes of the bone marrow were identical being, consequently, elements of the same tumor clone. PMID- 8211778 TI - [The morphofunctional properties of the blood cells and iron metabolism in the native inhabitants of the Taimyr Autonomous Okrug]. AB - The peripheral blood was studied in Dolgans, Nganasans and Nenetses, the native population living in Taimyr peninsula. The composition of their blood is really different from the European norm. In Aboriginals of Taimyr the activity of erythropoietin in blood plasma, the concentration of reticulocytes, the circulation in peripheral bed of diskocytes with one and many diverticula, the content of fetal hemoglobin are raised more than two times. The prevalence of iron deficiency anemia among the native population of Taimyr Autonomous Area is larger, than in Russia and in Aboriginals living in Evenkia and Yakutia. PMID- 8211779 TI - [Koln hemoglobinopathy: 3 patients in one Russian family]. AB - A rare disease with autosomal dominant inheritance was diagnosed in mother, her son and daughter. The condition was due to unstable hemoglobin Koln in 10% quantity. Clinical symptoms manifested most dramatically in a son, moderately in a daughter and slightly in a mother who had undergone splenectomy. All the hemolytic rises were provoked by antipyretics or, in occasional cases, by respiratory viral infections running with hyperthermia. To alleviate the symptoms, the son is scheduled for splenectomy. PMID- 8211780 TI - [The first case of Hb Camden carriage in Russia]. AB - Structural hemoglobinopathy due to carriage of Hb Camden was diagnosed in a male patient and his mother. Anomalous Hb was detected after a detailed analysis of the clinical evidence, blood smears microscopy, marrow examination, data obtained by a complex of methods to identify unstable Hb. It was defined as Hb Camden beta 131 GLN-->GLU. The carriage of this variant brings no clinical manifestations, but leads to impaired red cells morphology, decline of their life span, enhanced hemolysis. These properties are typical for mutant Hb lacking stability. Hb Camden carriage is considered as a compensatory hemolytic process. PMID- 8211781 TI - [The morphofunctional characteristics of the bone marrow erythroid cells in some forms of the myelodysplastic syndrome]. AB - Refractory anemia (RA) and RA with blast excess (RABE) showed inhibited proliferation of bone marrow erythroid cells (EC), the lowest values being in RABE. The latter, however, was accompanied with the highest count of PAS-positive EC, uneffective erythropoiesis being present in both RA and RABE. In sideroblast anemia the above proliferation was also inhibited, but uneffective erythropoiesis played much more pronounced role in pathogenesis of this anemia than in RA and RABE. The percentage of PAS-positive EC averaged 39.0%. The findings contribute to more profound understanding of anemia arising in myelodysplasia syndrome, to more accurate evaluation of therapeutic effect and prognosis in the above disease. PMID- 8211782 TI - [The clinical characteristics, complications and therapeutic problems of protein C deficiency]. AB - Examination was performed of 20 patients from 15 families with heterozygous deficiency of protein C (27-62% against the mean standard). Recurrent thromboses were seen in 17 of them. Thromboses of the lower veins, pulmonary artery thromboembolism, thromboses of the surface veins, those of cerebral vessels, myocardial infarction, of renal and mesenterial vessels were registered in 15, 5, 4, 3, 3, 1 and 1 patients, respectively. There was a tendency to recurrent thrombosis during pregnancy with high risk of spontaneous or induced abortions. The highest effect was produced with low-molecular heparin combined with transfusions of recently frozen plasma and introduction of disaggregating agents. Anabolic hormones were used to prevent thrombosis. The data are provided on a 4 fold increase in the prevalence of protein C deficiency in polythrombotic patients living in the West Siberia vs. deficiency of antithrombin III. PMID- 8211783 TI - [The effect of fibronectin on hematopoiesis in long-term cultures of the bone marrow from patients with acute leukemias in the remission stage]. AB - Hemopoietic effects in bone marrow long-term cultures (BMLTC) of healthy subjects and patients with acute myeloid leukemia (AML) in remission were studied due to fibronectin (FN) and glycoprotein of extracellular matrix of stromal microenvironment. Twelve AML patients and 6 healthy donors of allogenic transplant were examined. Blood formation in the BMLTC was assessed by weekly production of cells in nonadhesive BMLTC fraction and the content of granulocytic macrophagal colony-forming cells in it. The response of hemopoietic stroma on FN sublayer was evaluated by weekly measurements of BMLTC adhesive layer cellularity. FN is demonstrated to stimulate the growth of BMLTC adhesive cell sublayer, the cellularity increase being the same in the above groups. FN sublayer had no influence on cellularity of the nonadhesive fraction and on the number of granulocytic-macrophagal colony-forming cells in healthy subjects, whereas it increased these values in AML patients in remission. This rise, however, was not significant. BMLTC is capable of defining a favorable effect of FN sublayer on hemopoiesis in AML patients in remission. This effect may arise from higher quality of the sublayer and survival of cells-precursors at initial stages of the cultivation. PMID- 8211784 TI - [The neutrophil antibacterial function of patients with chronic bronchitis. Its immune correction by using inflammatory cytokines and allogeneic lymphocytes in vitro]. AB - In patients with acute and chronic bronchitis decreased neutrophil phagocytic, induced O2-dependent metabolic, bactericidal activity and the content of lysosomal cationic proteins, increased spontaneous O2-dependent metabolic activity were revealed. The most pronounced neutrophil functional disorders were detected in patients with chronic obstructive bronchitis (COB). The use of human immunoregulatory recombinant cytokines (interleukin-1 beta, interferon-gamma, tumor necrosis factor alpha) failed to augment in vitro suppressed neutrophil antibacterial (phagocytic) activity in patients with COB. These patient's neutrophil antibacterial activity restored in vitro in the presence of allogeneic (nonactivated or interleukin-2-activated) lymphocytes. The data obtained provide evidence for healthy donor's lymphocytes use in immunocorrection of patients with chronic bronchitis. PMID- 8211785 TI - [Bone marrow transplantation in acute leukemias: the arguments pro and con]. PMID- 8211786 TI - [The rheumatological masks of endocrine diseases]. PMID- 8211787 TI - [Physiological valvular regurgitation in healthy persons (its prevalence, hemodynamic characteristics and differential diagnosis)]. AB - Two-dimensional Doppler echocardiography (DECG) was employed to examine for valvular regurgitation 100 healthy subjects. Physiological valvular regurgitation (PVR) was detected in 32 of them. It was defined as isolated pulmonary, isolated tricuspid, combined tricuspid and pulmonary, mitral in 17%, 9%, 4% and 2% of the examinees, respectively. Hemodynamically, PVR was characterized by low maximal speed of the flow and minimal extension. It should be noted that similar hemodynamic DECG parameters can be registered in minimal aphonic valvular regurgitation arising in latent rheumatic and viral endocarditides. This fact must be taken into consideration when making the differential diagnosis. PMID- 8211788 TI - [The use of diflucan in myelotoxic agranulocytosis]. PMID- 8211789 TI - [Acute kidney failure due to obstruction of the upper urinary tract during the use of aminocaproic acid]. PMID- 8211790 TI - [Therapeutic plasmapheresis in the combined therapy of systemic lupus erythematosus (a case report)]. PMID- 8211791 TI - [The current chemotherapy of acute myeloid leukemias in adults]. PMID- 8211793 TI - [The effect of fraxiparin on thrombocytic-vascular hemostasis in patients with unstable stenocardia]. AB - Clinical examination of 25 males with new-onset and progressive angina pectoris resistant to inpatient combined antianginal treatment versus 15 healthy males established hyperfunction of the platelets in low antithrombogenic activity of the vascular walls in patients with unstable angina pectoris. A 5-day course of fraxiparin resulted in a trend to a decrease in ADP-induced platelet aggregation and in the level of platelet factor IV. The endothelium recovered normal antiaggregation and fibrinolytic properties. This may underlie the drug efficacy against unstable angina pectoris. PMID- 8211792 TI - [The role of lipid peroxides and blood rheological disorders in the pathogenesis and clinical course of ischemic heart disease]. AB - Combined assessment of primary and secondary products of lipid peroxidation, functional activity of red cells has been conducted in 130 patients with ischemic heart disease running different courses. Lipid peroxidation was found enhanced both in the whole blood and red blood cells. Blood rheology got abnormal. It is shown that lipid peroxides are involved in damaging erythrocytic membrane structure and function, thus promoting the progression of ischemic heart disease. PMID- 8211794 TI - [Left ventricular function in patients with arterial hypertension during the performance of acute drug tests with captopril and nifedipine]. AB - An examination was made of 22 hypertensive patients with clinical and echoCG symptoms of left ventricular hypertrophy. All the patients underwent coronary angiography, transvenous multiphase left ventriculography and acute captopril (11 patients), nifedipine (11 patients) tests. A single oral 25 mg dose of captopril increased energetic efficacy of cardiocycle, restored diastolic function of the left ventricle, aroused myocardial contractility. PMID- 8211795 TI - [The nondrug treatment of hypertension patients by their adaptation to periodic hypoxia in a barochamber]. AB - Patients with essential hypertension were exposed to periodic hypoxia in a pressure chamber. It is shown that adaptation to periodic hypoxia results in improvement of general condition of patients who exhibited a decline in blood pressure, minute blood volume, serum sodium concentrations as well as better microcirculation and tissue oxygen tension. Reduced concentrations of total serum cholesterol and atherogenic index were achieved in hypercholesterolemia patients. The changes obtained permitted reduction of hypotensive maintenance treatment. In view of positive results in hypertensive subjects, adaptation to periodic hypoxia in a pressure chamber is recommended for inclusion into combined regimens of hypertension therapy. PMID- 8211797 TI - [The choice of the most effective drug preparation and the assessment of its possible side effects]. PMID- 8211796 TI - [A comparative evaluation of the electric impulse treatment of atrial fibrillation based on the data from 2 clinics. 2. The late results]. AB - Long-term results of electroimpulse treatment for cardiac fibrillation in 1292 patients performed in cardiological clinics of Moscow and Kaunas have been compared. It is shown that more strict selection, longer preparation for the impulse exposure may secure a significant decrease in the number of the fibrillation recurrences both 1 and 6 months after recovery of the normal rhythm. PMID- 8211798 TI - [The use of the Lipostabil preparation in the combined efferent therapy of the clinical manifestations of an atherosclerotic process]. PMID- 8211799 TI - [The pharmacodynamics of theophylline (euphylline)]. AB - A single intravenous administration of 2.4%-10.0 euphylline to 35 patients with obstructive affections of the lungs entailed a broncholytic effect in large airways in patients with reversible obstruction under sub-therapeutical theophylline concentrations in the serum. In patients with mixed type of the obstruction and restrictive disturbances ineffective ventilation got worse, ventilation-perfusion relations disagreed, hemoglobin affinity to oxygen grew, pulmonary artery pressure dropped against the signs of pulmonary hypertension, EEG changed according to asynchronism pattern corresponding to brain hyperactivity. There was also elevation of both norepinephrine and epinephrine serum levels due to slow parenchymatous hepatic circulation which inhibited clearance of the substances. There was no relationship between changes in the indices and theophylline concentrations in the range 3.8-8.8 micrograms/ml. PMID- 8211800 TI - [The efficacy and safety of the drug treatment of cardiovascular diseases]. PMID- 8211801 TI - [The comparative efficacy of the prolonged-action theophylline preparations Theopek and Euphylong in elderly patients with chronic obstructive lung diseases]. AB - A randomized trial of long-acting theophylline drugs theopek taken twice daily and euphilong taken in a single daily dose has been performed in 59 elderly patients suffering from bronchial asthma, chronic obstructive bronchitis. The drugs' doses were adjusted to blood theophylline concentrations, clinical response, side effects. Theophylline concentrations were maintained in therapeutic doses. A 24 hour monitoring showed the highest concentrations of theophylline to be achieved at night and early in the morning in the group of patients on euphilong. A clinical response with improvement of external respiration became evident by the treatment day 5 and persisted by day 90. Side effects were not severe. Both the drugs are recommended for long-term treatment. When euphilong was given in a single evening dose, its efficacy was superior at night and early in the morning making the drug preferable in patients with night asthma. PMID- 8211802 TI - [The validation and procedure of inhalation therapy using 2-component aerosols in obstructive bronchopulmonary diseases]. PMID- 8211803 TI - [The potentials for treating patients with a recurrent course of chronic gastric erosions with the use of low-energy laser radiation]. PMID- 8211804 TI - [The correction of motor-tonic disorders of the gastrointestinal tract and of duodenogastric reflux with laser radiation]. AB - Forty-five patients with duodenogastric reflux and defective gastroduodenal motor tonicity (gastroduodenal hypotonia, duodenal hypertension, gastric hypotonia in combination with duodenal hypertension) were exposed to He--Ne laser radiation. The impact was focused on the biologically active points G14, TR5, VC15, E21. The treatment resulted in normalization of the gastrointestinal pressure gradient, in discontinuance or reduction of duodenogastric reflux. PMID- 8211805 TI - [The treatment of primary biliary liver cirrhosis with rifampicin]. AB - Seven patients with primary biliary cirrhosis were treated with rifampicin administered for 2 weeks in a daily dose 450-600 mg. Due to the treatment the itch disappeared completely in 4 and decreased significantly in 3 patients. As shown by the antipyrine test, half-life and clearance of antipyrine returned to normal suggesting cytochrome P-450 induction as a result of hydroxylation activity. There was a tendency to lowering of bilirubin, cholesterol, alkaline phosphatase, asparagine--and alanine aminotransferase against an increase in gammaglobulins. The differences were, however, insignificant. Rifampicin tolerance was satisfactory. PMID- 8211806 TI - [The treatment of osteoarthrosis deformans by needle-jet intra- and periarticular drug injections]. AB - The paper reports pilot experience with jet needle drug injections for knee joint osteoarthrosis deformans running with proliferative involvement. The treatment was performed outpatiently in the disease exacerbations associated with reactive synovitis. Injections of 20 mg kenalog were made with the semiautomatic combined jet injector ISI-I. 24 patients received 71 injections (a mean of 2.1 injections, each). Basic therapy underwent no changes. The course of injections produced improvement in 21 patients (87.5%). The majority of them got better as early as the first injection: arthrosis symptoms and pain alleviated, joint hyperthermia reduced, the mobility, on the contrary, increased. Blood counts showed no negative trends. Complications and exacerbations due to the treatment were not reported. Because of the efficacy, easy performance, painlessness, jet intra- and periarticular injections are believed beneficial and can be used outpatiently. PMID- 8211807 TI - [The level of serum thymic activity in patients with rheumatoid arthritis and systemic lupus erythematosus]. AB - Thymic serum activity (TSA) has been studied in 52 healthy subjects, 48 rheumatoid arthritis patients and 17 sufferers with systemic lupus erythematosus aged from 18 to 70. TSA was compared in patients under and over 40 years. In those under 40 TSA appeared significantly inhibited, while in older subjects it did not differ from age-matched control. No correlations were reported between TSA levels and clinical characteristics. Changes in TSA levels may be related both to low content of thymic hormones and formation of inactive complexes from thymic mediators with inhibitors. PMID- 8211808 TI - [A comparative evaluation of the clinical use of dobutamine and dopamine in patients in the early postoperative period]. PMID- 8211809 TI - [Systemic thrombolytic therapy in acute myocardial infarct: its effect on left ventricular function, body oxygen consumption and disease prognosis]. AB - Echocardiography, integral rheography of the body, Holter monitoring, assessment of oxygen consumption and blood gases were used in examination of 93 patients with macrofocal myocardial infarction (MI). 48 patients received thrombolytic therapy (TT) within 6 hours of MI which in 27 patients implied standard drugs (streptodecase, celiase, avelysin) and new medicine APSAC (21 patients). 45 patients received no TT. It was found that in acute MI period systemic TT prevented a fall in left ventricular performance, promoted advanced oxygen supply due to intensified oxygen extraction by tissues. This fact is attributed to transient changes in blood rheology. Application of APSAC prevented inhibition of myocardial contractility and development of congestive heart failure in subacute MI period. TT patients demonstrated ventricular arrhythmia on MI day 1 more often though by the number of the main arrhythmia types the groups differed insignificantly. Within 1-year postmyocardial infarction period TT patients had less repeat MI and were less frequently diagnosed to develop congestive heart failure. PMID- 8211810 TI - [A case of the lumbago-hematuria syndrome in a young man]. PMID- 8211811 TI - [The use of clindamycin in therapeutic practice]. PMID- 8211812 TI - [Current approaches to treating gallstones]. PMID- 8211814 TI - Capitation is misunderstood. PMID- 8211813 TI - Nitrous oxide: a serious look at laughing gas. AB - The purpose of this manuscript is to review the history, indications, and contraindications of nitrous oxide/oxygen as a conscious sedative agent. Included is a discussion of its addictive potential and the implications of its utilization with individuals who are recovering from addictive diseases. Additional discussion is devoted to the myeloneuropathies resulting from sustained "recreational" use. Particular attention is directed to dental personnel, the population with the greatest risk for addiction. PMID- 8211815 TI - The Texas Dental Peer Assistance Program and the impaired dental professional. AB - Chemical dependence is a devastating disease that, unless some form of intervention and treatment takes place, will ultimately destroy a person's life. Dentists are not immune to this malady. In fact, certain conditions of heredity, relative affluence, lifestyle, and drug availability may make them more susceptible. The Texas Dental Peer Assistance Program was formed to assist dentists who have a drug problem and whose goals include getting their lives back in order. Hopefully, this article will introduce this valuable program to those in need of its services. PMID- 8211816 TI - The teratogenic effects of salicylic acid on the developing nervous system in rats in vitro. AB - Aspirin ingestion in humans and animals has been reported to lead to a range of undesirable outcomes, including fetal death, growth retardation, and congenital abnormalities. Rat embryos were cultured for 48 h in 100-300 micrograms/ml of salicylic acid, a metabolite of aspirin, days 9.5-11.5 of gestation. When compared to growth in control embryos, a significant dose-dependent decrease in crown-rump lengths, somite numbers, and yolk sac diameters was observed. There was also a significant increase in overall dysmorphology, including eye, brachial arch, and heart anomalies, and an absence of forelimb buds. The neural tube was especially vulnerable and had frequently failed to close. Cellular and ultrastructural examination revealed extensive cell death in the neuroepithelium, with a lesser effect on the mesenchymal cells. Large condensed blebs projected into the ventricular lumen, and cell membranes as well as the basal lamina were severely disrupted, with all cytoplasmic organelles affected in dying cells. It is likely that the extensive cell necrosis and blebbing in the developing neuroepithelium at the site of neural tube fusion may be involved in failed neurulation, while necrosis at other sites in the cranial neuroepithelium may be linked with previously reported intellectual and behavioural abnormalities. PMID- 8211817 TI - Methyl methacrylate: inhalation developmental toxicity study in rats. AB - Methyl methacrylate (99.9% pure) was administered by vapor inhalation exposure to five groups (27 rats/group) of presumed pregnant rats (Crl:CD) at concentrations of 0 (control), 99, 304, 1,178, and 2,028 ppm for 6 hr/day on days 6-15 of gestation (G). Maternal body weight, feed consumption, and clinical signs were recorded throughout gestation. Dams were euthanized on day 20 G. Each uterus was weighed and corpora lutea, implantation sites and resorptions were counted. The number of fetuses per litter were counted and their location within the uterus recorded. All fetuses were weighed, sexed and examined for external and skeletal alterations. One half of the fetuses from each litter were examined for visceral alterations. No treatment-related deaths were noted at any concentration tested. Treatment-related effects on maternal body weight and feed consumption were noted at all exposure levels. The decreases in maternal body weight at 99 and 304 ppm were minimal and transient since they returned to control values by the next weighing period. When exposure was discontinued, body weight gain and feed consumption in all exposure groups returned to control values. There were no treatment-related changes in the number of litters produced or in the mean number per litter of corpora lutea, implantations, resorptions, live or dead fetuses, or sex ratio. Fetal body weights were similar between the control and treated groups. There were no treatment-related increases in the type or incidence of external, visceral, or skeletal malformations, developmental variations, or variations indicative of retarded development. Exposure to methyl methacrylate concentrations up to 2,028 ppm resulted in no embryo or fetal toxicity or malformations even at exposure levels that resulted in maternal toxicity. PMID- 8211818 TI - Sodium valproate-induced cardiovascular abnormalities in the Jcl:ICR mouse fetus: peak sensitivity of gestational day and dose-dependent effect. AB - Sodium valproate was administered to Jcl:ICR mice in order to determine its effect on cardiovascular development. A single dose of 600 mg/kg of sodium valproate was injected intraperitoneally on gestational days 6, 7, 8, or 9. In same animals, a single dose of 300, 400, 500, or 700 mg/kg was injected on gestational day 7. On day 18 of gestation, dams were laparotomized to observe number of live, dead and resorbed fetuses. In addition, live fetuses were examined for cardiovascular abnormalities. Although cardiovascular abnormalities were noted in 3% of live fetuses and in 26% of litters in the group treated on day 6 (600 mg/kg), there was no significant difference from the control group, suggests that there may have been a biologically significant increase, although not a statistically significant increase. Cardiovascular abnormalities were found in 30%, 11%, and 8% of live fetuses in the groups treated with 600 mg/kg on days 7, 8, and 9, respectively. These represented a statistically significant increase in effects as opposed to the control groups. Among the varying dosages administered on day 7 of gestation, cardiovascular abnormalities occurred in 2%, 6%, 16%, and 36% of live fetuses in groups treated with 300, 400, 500, and 700 mg/kg, respectively, showing a significant dose-dependent increase. These cardiovascular abnormalities observed were divided into the following groups: ventricular septal defect, endocardial cushion defect, transposition of the great arteries, double outlet right ventricle, tricuspid atresia, and hypoplastic left heart syndrome. Maternal death did not occur at any treatment level. PMID- 8211819 TI - Prevention by Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate) of vanadate induced developmental toxicity in mice. AB - Vanadate is embryotoxic and fetotoxic in golden hamsters, mice and rats. Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate), a chelating agent widely used in analytical chemistry, is an effective antidote in the treatment of oral or parenteral vanadate poisoning. The present study evaluated the effect of administration of Tiron on sodium metavanadate (NaVO3)-induced developmental toxicity in mice. NaVO3 (25 mg/kg, i.p.) was injected on day 12 of gestation, whereas Tiron was injected subcutaneously at 0, 24, 48, and 72 hr after NaVO3 administration. Tiron effectiveness was assessed at dosage levels of 0, 250, 500, and 1,000 mg/kg. Cesarean sections were performed on gestation day 18. All live fetuses were examined for external, internal, and skeletal malformations and variations. Amelioration by Tiron of NaVO3 developmental toxicity was evidenced by a significant decrease in the number of resorbed fetuses, an increase in the mean fetal weight, and a reduction in the incidence of the skeletal variations caused by NaVO3. According to these results, Tiron offers encouragement with regard to its therapeutic potential for pregnant women exposed to vanadate. However, further investigations, including the effect of increasing the time interval between acute vanadate exposure and initiation of Tiron therapy, are required. PMID- 8211820 TI - Effects of sodium bicarbonate and ammonium chloride on the incidence of furosemide-induced fetal skeletal anomaly, wavy rib, in rats. AB - Furosemide produces fetal wavy ribs when administered to pregnant rats during late gestation. The compound is also known to produce metabolic alkalosis in laboratory animals and man. In order to evaluate the effect of furosemide on maternal blood pH, Crj:CD(SD) female rats received an oral administration of 150 or 200 mg/kg of furosemide by gavage on day 16 of gestation and were bled at 4 hr post-dose. Compared to an average pH of 7.39 in control females, there was a significant elevation in blood pH in these furosemide-treated females (average pH of 7.44 to 7.48). When 2% sodium bicarbonate was provided in the drinking water for females treated with 150 mg/kg of furosemide, there was a further rise in maternal blood pH (7.52) compared to females treated with furosemide alone. Associated with this elevation in maternal blood pH was a marked increase in the incidence of fetal wavy ribs (87.6% compared to 27.6%). When females treated with 200 mg/kg of furosemide were provided with 0.5% ammonium chloride, furosemide induced maternal alkalosis was corrected (pH decreased to 7.35) and there was a reduction in the incidence of fetal wavy ribs (7.0% compared to 37.2%). In addition, maternal blood pH among individual females was positively correlated with the incidence of fetal wavy ribs (r = 0.714). These results suggest that maternal metabolic alkalosis is involved in the pathogenesis of furosemide induced wavy ribs. PMID- 8211821 TI - Teratogenicity and developmental toxicity of carbon monoxide in protein-deficient mice. AB - Experiments were carried out to determine the teratogenicity and developmental toxicity of carbon monoxide (CO) in mice fed protein-deficient diets. Pregnant CD 1 mice were fed 27 (control), 16, 8, or 4% protein diets throughout gestation and each group was exposed to 0 (control), 65, 125, 250, or 500 ppm of CO from gestation days 8-18. The CO exposure was continuous except for daily watering, feeding or cage changing. The animals were killed on gestation day 18. Pregnancy status of the dams was examined. Fetuses were examined for gross and skeletal malformations. The percentages of dead or resorbed fetuses and of grossly malformed fetuses per litter were related to the CO exposure levels and inversely related to the dietary protein levels. All levels of CO and 8 or 4% protein diets significantly decreased the fetal weight of normal fetuses. The most commonly seen gross malformations were brachygnathia accompanied by protruding tongue, microstomia, microcephaly, open mouth, or open eyes. Most of the grossly malformed fetuses also had dry, bleached and wrinkled skin. An increased incidence of skull (interparietal or supraoccipital), and jaw (mandible or premaxilla) malformation; wavy ribs and scoliosis of spine; and limb unossifications were observed in the litters of dams fed protein-deficient diet and all levels of CO exposure. Malformed litters in each protein diet were related to CO exposure levels. The data suggest that CO is teratogenic under protein-deficient conditions. Protein deficiency had additive effect on CO teratogenicity and synergistic effect on fetal mortality. Special groups at risk may include cigarette or marijuana smokers and malnourished or undernourished populations. PMID- 8211822 TI - Effects of fetal dexamethasone exposure on postnatal control of cardiac adenylate cyclase: beta-adrenergic receptor coupling to Gs regulatory protein. AB - In the adult, glucocorticoids have been shown to upregulate beta-adrenergic control of adenylate cyclase by a variety of mechanisms; glucocorticoids are also thought to play a role in development of cardiac adrenergic function. In the current study, pregnant rats were given 0.2 mg/kg of dexamethasone on gestational days 17, 18, and 19 and the effects on the development of cardiac beta-receptors and their linkage to the stimulatory G-protein, Gs, were examined at 4 days postpartum. beta-Receptor numbers and affinity were unaffected by dexamethasone exposure, nor was there any change in the ability of the GTP analog, Gpp(NH)p, to shift the affinity state of the receptor. Addition of Gpp(NH)p to cardiac membranes enhanced basal and isoproterenol-stimulated adenylate cyclase activity, but the total response to isoproterenol, with or without Gpp(NH)p, represented a very small fraction of total enzymatic activity. Quantitative analysis of Gs indicated no changes attributable to dexamethasone treatment. Although prenatal dexamethasone has been shown to increase adenylate cyclase reactivity to beta adrenergic input, the effect appears to be at the level of the catalytic subunit of adenylate cyclase, rather than at receptor or G-protein stages. PMID- 8211823 TI - What is the relationship between birth defects and pregnancy bleeding? New perspectives provided by the NICHD workshop dealing with the association of chorionic villous sampling and the occurrence of limb reduction defects. PMID- 8211824 TI - A case of a closed partial cloacal septation defect with a patent urachus. AB - A boy with a closed partial cloacal septation defect with a patent urachus is reported. He had an intact abdominal wall, a patent urachus, a colovesical fistula, intact genitalia and urethra, imperforate anus, and a lipomyelocystocoele. Patients with similar constellation of findings have been reported as cloacal exstrophy variants. What distinguishes this case from the other reported variants is the intact abdominal wall with the patent urachus, the small and normally formed phallus and urethra, and the presence of a lipomyelocystocoele. We discuss the possible embryologic mechanism responsible for this boy's findings and possible relationship with the cloacal exstrophy spectrum. We also discuss new terminology for the epispadias-exstrophy spectrum. Furthermore this case reminds us that there is considerable variability within the epispadias-exstrophy spectrum. PMID- 8211825 TI - Medicine wins big in 73rd legislature. PMID- 8211826 TI - Blood donor bill becomes law. PMID- 8211827 TI - Delegates support school-based clinics. PMID- 8211828 TI - Doctor gets injunction against anti-abortion protestors. PMID- 8211829 TI - Federal and state laws prohibit some debt collection practices. PMID- 8211830 TI - When patients file bankruptcy. PMID- 8211831 TI - A day and a night with Texas physicians. PMID- 8211832 TI - House of Delegates studies physician impairment. PMID- 8211833 TI - House of Delegates passes policy statement on health-system reform. PMID- 8211834 TI - Initial STD visits by adolescent females, Dallas County, Texas. AB - Sexually active adolescents are at high risk for unintended pregnancy and sexually transmitted diseases. We identified a cohort of 6089 women aged 13 to 21 years who in 1985 either delivered an infant at Parkland Hospital (3154) or used the outpatient clinics (2935). We reviewed those records and others in the Dallas County sexually transmitted disease (STD) clinic for the period 1983 through 1988 to determine the prevalence of visits to the Dallas County STD clinic by pregnant and nonpregnant adolescents, STD diagnoses at initial visit, whether STD visits and diagnoses varied by pregnancy status or ethnic background, and how the women were referred to the STD clinic. Similar percentages of nonpregnant (13%) and pregnant (11%) women had an STD visit, and most adolescents who visited the STD clinic had an STD diagnosis made. Gonorrhea and syphilis were the STDs diagnosed most frequently in both pregnant and nonpregnant adolescents. Regardless of pregnancy status, black adolescents were 7.3 times more likely to have an STD visit. Referral by a sexual partner was the second most common reason that adolescents sought STD care. Our study provides only minimal estimates of STDs among adolescents but indicates STDs, regardless of pregnancy status, are a more common medical problem than has been reported previously. Referral by sexual partners may be an important way to reach adolescents at risk for STDs. PMID- 8211835 TI - Physical and psychosocial needs of cancer patients. AB - A collaborative multidisciplinary study was conducted to assess both physical and psychosocial needs of 117 adults with various types of cancers. Although these patients functioned adequately in many areas of their lives, they reported that cancer and its treatment had an impact on energy, physical and recreational activities, communication with spouse, sexual and emotional functioning, occupational matters, and treatment-related situations. Younger patients reported more psychosocial, sexual, and treatment-related problems than did older patients. Female patients reported more chemotherapy-related problems than did male patients. Implications for clinicians treating cancer patients were discussed. PMID- 8211836 TI - It's time for physicians to be heard. PMID- 8211837 TI - Physicians should participate in gun safety education. PMID- 8211838 TI - Malpractice-system reform essential to health-system reform. PMID- 8211840 TI - [Injuries of the locomotor system]. PMID- 8211839 TI - Another chance for nurses with chemical dependencies. PMID- 8211841 TI - [Towards minimally-invasive osteosynthesis]. AB - While the original techniques of open reduction and internal fixation have proved their efficacy during the last decades, the development of new implants and techniques is mostly based on the experience, that soft tissues and local blood supply are the most important factors for undisturbed fracture healing. Unreamed nails with interlocking plates with limited bone contact as well as soft tissue preserving techniques with minimal fracture visualization and indirect or closed reduction techniques determine the current progress in internal fixation on the way to a minimal access invasive or biological technique. PMID- 8211842 TI - [What does the new solid unreamed tibia nail (UTN) contribute in open fractures?]. AB - In the field of trauma surgery open fractures of the lower leg remain an injury with a high complication rate. Bone and soft tissues must be treated carefully to avoid further damage, so that uncomplicated healing results. In the past, treatment of open fractures of the lower leg was done primarily by external fixation. Medullary nailing with reaming of the medullary canal has been widely used for shaft fractures without soft tissue damage, but when used in open fractures, the infection rate remained high. Intramedullary nailing without reaming required the development of new implants (i.e. the solid unreamed tibia nail (UTN) by AO). These new implants allow us to perform the nailing technique in open fractures of the lower leg with a low complication rate. This can be done primarily or secondarily after initial treatment with external fixation. Even patients with lower-leg open fractures may benefit from the advantages of early mobilization and partial weight-bearing after osteosynthesis with intramedullary nailing. PMID- 8211843 TI - [Advantages and disadvantages of various implants in fractures of the proximal femur]. AB - Fractures of the proximal femur can be stabilized by help of a number of implants. The choice depends on the site and the degree of instability of the fracture, the age of the patient, the state of the hip-joint cartilage, and last but not least on the preference of the surgeon for a certain type of osteosynthesis. PMID- 8211844 TI - [Distal radius fractures: conservative or surgical treatment?]. AB - The "classical" Colles fracture of the distal radius is the most common fracture in the adult. In order to reduce the still rather high rate of permanent disability, this fracture involving a functionally important joint requires accurate reduction. The AO-fracture classification introduced by Muller not only defines the severity of an injury, but also allows for decision-making as to the most adequate treatment. Besides the purely conservative management by closed reduction and plaster cast for the type-A fractures, we have a number of other treatment modalities for the more complex-B and C-type fractures, such as closed reduction and percutaneous K-wire application or the use of the small external fixator as well as open reduction and internal fixation by plates and screws for a few selected indications. PMID- 8211845 TI - [The surgical treatment of shaft fractures in childhood]. AB - The treatment of long bone fractures in children has been substantially changed within the past five years. The aim at conservative management, including closed reduction, retention and fixation, remains undebatable. Considerations of the biological and biomechanical healing process and the aim of short hospitalization and early mobilization have lead to an increased use of the intramedullary nailing technique. Simultaneously, the indication for osteosynthesis with plates has been limited to more restricted indications. The first multicentric results of the international working group of pediatric traumatology, together with our personal experience over 20 years, form the basis of a therapeutic concept for long bone fractures in children. Prospective studies of these recommendations will continuously analyse the quality assurance of fracture treatment. PMID- 8211846 TI - [Follow-up care of surgically-treated fractures and evaluation of healing process in the roentgen picture]. AB - The aim of surgical therapy of a fracture is the restoration of the original integrity of the limb. X-rays are the only means by which the surgeon can observe fracture healing over time. This includes direct bone healing without major radiological changes and indirect bone healing which shows callus formation. The two requirements needed for rapid bone remodelling and early mobilization after operation are an exact repositioning of the fracture fragments, if possible, and the maintenance of soft tissue and joints. Postoperative findings, complications and aftertreatment are discussed. X-ray series are presented, and the differences in fracture healing are shown. PMID- 8211847 TI - [Management of patients with multiple injuries]. AB - In severe trauma dead tissue, pain, stress, hemorrhage and ischaemia-reperfusion injury put an 'antigenic load' on defense systems which may result in 'host defense failure disease' and multiple systems organ failure. Surgical management must eliminate or reduce 'antigenic load' as soon as possible. Besides shock treatment, control of hemorrhage and repair of hollow viscus injuries, unstable 'central' fractures must be fixed, dead tissue removed and compressed muscle compartments released. Fracture fixation in multiple trauma requires modifications concerning monitoring, positioning and operative methods. PMID- 8211848 TI - [Complex internal knee lesions--diagnosis, indications and timing]. AB - Ligamentous knee injuries are nowadays more often seen in the office of the family physician, mainly because of an increase in recreational sports injuries. With the help of a questionnaire one can obtain a reliable impression of the injury pattern. The clinical examination is performed in a standardized way, so even in acute ligamentous injuries a correct diagnosis can be obtained at the first examination. The diagnosis of an instability is made with an accurate clinical examination; in case of marginal cooperation of the patient the examination is performed under anesthesia. Depending on the findings, the definitive operation will follow at the same time. In case of a big hemarthrosis we recommend an a.-p. and a lateral X-ray of the knee joint for exclusion of a bony injury before proceeding with the clinical examination. An arthroscopy is indicated in effusions of unclear origin, in the suspicion of meniscal or cartilaginous damage, in a stable knee with hemarthrosis and before definitive stabilization of complex injuries to exclude further damage to other intraarticular structures. Acute ACL ruptures are only operated on in case of bony avulsion fractures, in persons very active in sport and in case of relevant concomitant injuries. Medical collateral injuries without an ACL rupture are usually treated conservatively, except if there is an additional peripheral tear of the meniscus. PCL injuries are seldom operated, except if there is a complex concomitant instability. We aim for an early reconstruction within two weeks after the accident. PMID- 8211849 TI - [Arthroscopy of smaller joints: hand, elbow and ankle arthroscopy]. AB - These joints are accessible, though technically demanding, by arthroscope. Above all, the evaluation of the lesions is not simple. Arthroscopy always represents the last diagnostical alternative. The extraction of loose fragments, the debridement, the shaving and the treatment of infections are excellent indications. Postoperative rehabilitation is favoured and shortened with the arthroscopic approach. Elbow arthroscopy did not greatly, develop during the last years. Posttraumatic situations, corpora libera and cartilage lesions represent the main indications. The arthroscopies of the ankle and the wrist, however, are increasing. Carpal instability and discus problems of the wrist are quite interesting. Lately, endoscopic carpal-tunnel decompression has been propagated, but is still in its experimental phase. At the ankle, osteochondrosis dissecans, flake fracture and fibrosed plica [discovered through arthroscopy, mostly in athletes] are suitable for arthroscopic removal or reconstruction. Interfering osteophytes at the anterior border of the tibia can also be removed arthroscopically. Percutaneous internal fixation and fusion of the ankle joint need first to be evaluated in a long-term follow-up. Arthroscopic debridement and rinsing against infections are quite successful for all the joints. The arthroscopy of a small joint is technically quite demanding; therefore, it should be practised only by a few specialized centres. PMID- 8211850 TI - [Quality control and cost-benefit analysis in surgical fracture treatment]. AB - In recent years quality assurance is gaining increasing importance in all parts of medicine. In this article, different quality control measures in the field of operative fracture treatment are reviewed and illustrated. As in most other therapeutic specialties, the most commonly used measures are sporadic quality control studies. The Documentation Center of the association for the study of internal fixation [AO] offers in addition to all its contributing clinics an extraordinary measure for a continuous control of their treatment results. So far only a few instances of cost-benefit analysis have been published. Besides direct comparison of costs of different treatment options, improved quality of life may be calculated as well, using the method of Quality-Adjusted Life Years [QALY]. PMID- 8211851 TI - [The history of gallstone manifestations]. PMID- 8211852 TI - [Analysis and epidemiology of gallstones in deceased and autopsied patients of the Thurgau canton]. AB - In our postmortem examinations of patients in the canton of Thurgau from May 1989 through December 1991 we found a cholelithiasis or a condition after a cholecystectomy of gallstones in 44% of the women and 23% of the men. While gallstones were found in only 11% of the women and 7% of the men up to age 50, half of all women and every third man in the age group over 90 had gallstones. Among the gallstone carriers, 8% of the women and 2.5% of the men had developed a gall bladder--gall duct carcinoma. Where a liver cirrhosis was present, gallstones occurred at nearly the same rate in both sexes (45%/44%). 33% of the persons with gallstones had a solitary stone, and 31% had more than 10 stones. More than a third of all stones had a cholesterol content of more than 80%, and every seventh stone had a bilirubin content higher than 80%. The calcium content of more than 40% of the stones exceeded 5%. The examination for bilirubin can be easily performed with some exercise by means of the bilirubin test field on the urine sticks supplied by the Boehringer Mannheim company. PMID- 8211853 TI - [Pathophysiology of gallstone formation]. AB - There are two types of gallstones: cholesterol and pigment stones. The pathogenesis is divided into three phases: supersaturation, nucleation and stone growth. Hypersecretion of biliary cholesterol, crystallization promoting and inhibiting factors, gallbladder hypomotility, arachidonyl lecithin, prostaglandins, mucin and calcium play an important role in the formation of gallstones. For the formation of pigment stones a decreased secretion of biliary acids, an increased secretion of unconjugated bilirubin into the bile and an infection of the biliary tract are the most important causative factors. PMID- 8211854 TI - [Radiologic and ultrasound detection of gallstones]. AB - Ultrasonography (US) is the method of choice for evaluation of gallbladder stones with an accuracy of 96%. Number, size and calcification can be assessed by virtue of US reflection and attenuation. If more than five stones are present, the accuracy decreases. To determine the calcium content of stones more precisely, computed tomography can be used. This allows an assessment of the success rate of lithotripsy and chemolysis. Oral cholecystography is an alternative method of similar accuracy as US. It provides additional information about the patency of the cystic duct. In the presence of ductal stones, the accuracy of US decreases to 30%, mainly because of overlying bowel gas. Since 8 to 16% of all cases of cholecystolithiasis are accompanied by choledocholithiasis and since this entails a change in treatment, intravenous cholecystocholangiography with an accuracy of more than 90% is the method of choice in this case. Additionally, it provides knowledge on the biliary anatomy preoperatively. It does not, however, replace US, because opacification of the gallbladder is limited with this method. If intravenous cholecystocholangiography fails in case of impaired liver function, transcholecystic cholangiography or, in cases of dilated ducts, percutaneous transhepatic cholangiography can be used. Plain film radiography is not a suitable technique, since only 10 to 15% of all gallstones calcify. PMID- 8211855 TI - [Intraoperative cholangiography and ultrasound in laparoscopic cholecystectomy]. AB - For years there has been a controversy as to whether or not a routine peroperative cholangiography is indicated during conventional cholecystectomy. With the introduction of the laparoscopic technique, the reasoning has changed, but the controversy persists. The surgeon of today has the choice between two diagnostic modalities, which are to be presented here. Peroperative cholangiography was the technique usually employed during conventional operation. Many surgeons are in favor of routine intraoperative cholangiography during laparoscopic cholecystectomy. The goal of the examination is no longer the detection of unsuspected common bile duct stones, but the visualization of anatomical variations of the bile ducts and hepatic arteries for prevention of bile duct injuries. A difference in number of bile duct injuries in patients examined routinely or selectively has not yet been proven, so selective use of intraoperative cholangiography is still a safe strategy. A multitude of different catheters and introducer-sets for the laparoscopic operation are commercially available. We feel that a catheter should facilitate insertion without requiring the introduction of an additional cannula. An exception are the patients with known bile duct calculi, where a laparoscopic bile duct exploration is planned and the additional cannula is needed for this procedure anyway. Intraoperative cholangiography detects bile duct stones with a sensitivity of 95 to 100%. The sensitivity for the demonstration of anatomical variations of the bile ducts is smaller and anomalies of the arteries can not be demonstrated at all.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8211856 TI - [Anesthesia for laparoscopic surgery]. AB - A thorough understanding of the physiological repercussions of the pneumoperitoneum is essential in order ot properly grasp the safety rules governing anesthesia for laparoscopic surgery. As a general rule systemic vascular resistance increases as the heart flow rate and venous return circulation decrease. Variations in the ventilation/perfusion ratio explain the origin of hypercapnia observed in patients. There is little reabsorption of CO2 from the peritoneal cavity. However, this increases considerably if CO2 is insufflated outside the peritoneum (for example during pelvic lymph-adenectomy). Anesthesia must therefore limit the intra-abdominal pressure by adequate curarization and adapt the ventilation according to the P and CO2 capnographic readings. When the surgical procedure is protracted, it may be of benefit ot the patient to reduce systemic vascular resistance by using halogenic anesthetics such as isoflurane. PMID- 8211857 TI - [Does drug-induced litholysis still have a place in treatment of gallstones?]. AB - In past years, laparoscopic cholecystectomy has largely taken the place of conservative therapy. However, analysis of our data shows, that conventional litholytic therapy of cholesterol stones using bile acids: a) achieves a success rate of over 80%, as long as the patients are well selected prior to therapy (stones < 1 cm diameter, stone size < one fourth of gallbladder contraction of more than 50% as compared when fasting, isodensity of stones in CT) b) has a mortality rate of 0% c) has high patient compliance, because typical episodes of biliary colics and general dyspeptic complaints due to stones are reduced. Therefore, combination bile acid therapy for lysis of selected cholesterol gallbladder stones is still justified today. Particularly young women with small, suspended concrements or patients with recurrent cholesterol stones benefit by this treatment. Extracorporeal lithotripsy can be justified today only in combination with bile acid therapy. However, the number of treatable persons with gall stones is quite small (< 20% of all patients with stones), duration of therapy is three years and the recurrence rate 2-5 years after successful lysis is 25-50% (solitary stones recur less often than multiple ones). Considering a prevalence of 20% of persons with gall stones in the European Economic Community, there are 12 million patients potentially eligible for litholysis. PMID- 8211858 TI - [Extracorporeal shockwave lithotripsy of gallbladder calculi]. AB - Shockwave disintegration of gallbladder stones with lythic therapy of residual fragments is successful when all criteria of patient- and stone-selection, shockwave application and lysis are fulfilled. The "Four-S-stones" proved to be the best candidates: solitary, symptomatic, sonolucent in a sufficiently contractile gallbladder. The rate of complications is low. Stone recurrence rate (10 to 15% after three years) is much lower as in previous studies using lythic therapy only. The new therapeutic approach to gallbladder stone disease with fragmentation, spontaneous fragment-clearance and lysis of residual fragments is- as the only truly non-invasive procedure--for 10 to 20% of the patients an alternative equal to operation. PMID- 8211859 TI - [Laparoscopic cholecystectomy: results and complications--remaining indications for open cholecystectomy]. AB - Since the introduction in 1987, laparoscopic cholecystectomy (LC) became the method of choice to treat symptomatic cholecystolithiasis. The results of four multicenter studies show a morbidity rate of 3.0% and a mortality rate of 0.05%. Injuries to the common bile duct or to an accessory bile duct occurred in 0.43% of cases and were recognized and treated intraoperatively in 31.3%. Conversion to open cholecystectomy was performed in 4.9%. Patients were discharged to home after 3.0 to 4.4 days (european cases) and returned to full time employment 10 to 14 days following intervention. Indication for primary open cholecystectomy have become rare and include absolute contraindications to perform LC and relative contraindications, including certain cases of severe acute or chronic inflammation, especially when patients previously have undergone upper abdominal surgery. PMID- 8211860 TI - [Laparoscopic laser cholecystectomy]. AB - Although studies on laparoscopic cholecystectomy using laser surgery show no significant difference when compared to those done with cautery, the use of a laser does have substantial assets. A highly accurate dissection as well as coagulation of arteries up to a size 3 mm can be achieved if the appropriate type of laser is chosen. Our cases have shown us that trauma to the tissue due to laser surgery is minimal and causes less damage than when a monopolar hook electrode is used. The fact that patients with laser surgery have less pain than those where the operation was performed using the monopolar electrode has been noticed by various authors. The minor heat production and the better healing tendency after laser surgery may be an explanation of this phenomenon. PMID- 8211861 TI - [Training in minimally invasive methods within the scope of continuing education]. AB - Minimal invasive techniques must be trained in an early phase of surgical specialisation. These techniques are especially suited for the training of beginners, because they enforce a higher degree of manual skill than conventional operations and better 3-dimensional understanding of anatomy. Furthermore, most of the middle-sized visceral operations will be performed laparoscopically in future. PMID- 8211862 TI - [Extracorporeal shockwave lithotripsy of bile duct calculi]. AB - Shockwave therapy of bile duct stones is not dependent on difficult preconditions concerning stone-volume and -composition or subsequent lythic therapy. Its main indication is failure of endoscopic sphincterotomy (EST). Shockwave lithotripsy of bile duct stones--which may even be carried out even instead of EST in specific cases--is with a success rate of 80 to 95% as effective as shockwave lithotripsy in urology. PMID- 8211863 TI - [Laser lithotripsy in the treatment of bile duct calculi]. AB - Currently more than 90% of all common bile duct stones can be removed non surgically by means of endoscopic sphincterotomy, stone extraction and mechanical lithotripsy. For impacted, very large or very hard concrements intracorporeal shock wave lithotripsy by means of pulsed lasers represents a clinically newly established treatment procedure. Most clinical experience exists using the pulsed dye laser applied cholangioscopically via the endoscopic-retrograde or percutaneous-transhepatic route. The development of commercially available fine caliber-endoscopes allows a relatively easy access to the stone compared to conventional mother-baby-scope-systems. A new stone-tissue-detection-system (STDS) in combination with a rhodamine-6G dye laser is promising for "blind" laser-lithotripsy using standard ERCP- or balloon catheters or a special lithotriptor basket. After successful conclusion of our in vitro and animal studies concerning the STD system we report on 18 patients with giant common bile duct stones using STDS in combination with a Rhodamin-6G dye laser. PMID- 8211864 TI - [Therapy of bile duct calculi from the surgical viewpoint]. AB - Stones in the ductus choledochus can be managed endoscopic-retrograde, percutaneously-transhepatic (in case it is impossible to reach the papilla vateri) or surgically. If choledocholithiasis is found on performing a laparoscopic cholecystectomy management nowadays consists of splitting the therapeutic regimen: Laparoscopic cholecystectomy and postoperative ERCP and papillotomy. A one time surgical procedure is certainly going to be more frequent in the future: laparoscopic cholecystectomy and revision of the choledochus. This procedure has great advantages for the patient as it needs just a single operation and is easy on his papilla. The necessary laparoscopic instruments have to be perfected and the procedure demands a substantial amount of time plus a high surgical standard. PMID- 8211865 TI - After pneumonia... PMID- 8211866 TI - Chronic respiratory failure in COPD: is there a place for a respiratory stimulant? PMID- 8211867 TI - Factors of importance for the long term prognosis after hospital treated pneumonia. AB - BACKGROUND: Elderly patients admitted to hospital for community acquired pneumonia have a high risk of recurrence of pneumonia and of death during the years after discharge. In this study potential factors of importance for the long term prognosis after hospital treated pneumonia were retrospectively investigated. METHODS: A total of 241 patients (103 men) with a mean age of 60 (range 18-102) years discharged from hospital after treatment for community acquired pneumonia were studied. After an average follow up period of 31 months, 18 independent variables present during hospital treatment of the initial pneumonia were examined for association with the following end points: recurrence of pneumonia, death from any cause, and death from pneumonia. RESULTS: Age adjusted analysis showed that systemic treatment with corticosteroids correlated significantly with recurrence of pneumonia and with death. The presence of low serum albumin levels on admission or colonisation of the respiratory tract with Gram negative enteric bacteria seemed to be important negative prognostic factors for the outcome during pneumonia recurrences after discharge. CONCLUSIONS: Patients who are admitted to hospital with pneumonia are at risk of subsequent pneumonia and death after discharge. This risk seems to be even higher in patients who are treated with corticosteroids systemically, who have a low serum albumin level on admission, or who become colonised in the respiratory tract with Gram negative enteric bacteria during their hospital stay. PMID- 8211868 TI - Lung function in white children aged 4 to 19 years: I--Spirometry. AB - OBJECTIVE: A study was performed to produce reference standards for spirometric lung function in white children and to calculate standard deviation scores adjusted for gender and pubertal stage. METHODS: A cross sectional study was made of 772 white children aged 4.6 to 18.8 years (455 male) tested on an OHIO 840 spirometer and assessed anthropometrically and pubertally. RESULTS: Before puberty there was a linear increase in all lung function measurements with height. During puberty a sudden increase occurred, but subsequently the relationship was again linear. No simple single equation described this pattern. Advanced puberty in younger children conferred a respiratory advantage, whilst delayed puberty resulted in the converse. Girls had poorer volumes per unit height, but young girls had superior airflow/unit lung volume. In both sexes lung volumes and flows bore a constant relationship to external thoracic dimensions. CONCLUSIONS: Puberty has a dramatic effect on lung function. Regression equations for predicted values of lung function measurements and for calculation of standard deviation scores are given (with pubertal correction factors) for each gender. PMID- 8211869 TI - Lung function in white children aged 4 to 19 years: II--Single breath analysis and plethysmography. AB - OBJECTIVE: A study was performed to determine reference ranges for whole body plethysmographic gas volumes and single breath gas transfer in healthy prepubertal and pubertal schoolchildren. METHODS: The study was performed in 772 white London schoolchildren (455 male) who were clinically examined, assessed auxologically and, in 63% of cases, pubertally staged. Regression equations for the calculation of standard deviation scores were derived. RESULTS: Male lung function variables showed a discontinuous pattern of increase with standing height. Linear increases until puberty were followed by a sudden pubertal rise and a further increase with height which was more marked than before puberty. Correction for varying thoracic dimensions eliminated these changes. In females a smoother curvilinear relationship was observed with no correction possible for thoracic size. CONCLUSIONS: Male puberty leads to profound changes in pulmonary function mostly related to thoracic size, an effect not observed in females. PMID- 8211870 TI - Pattern of lung volumes in patients with sighing breathing. AB - BACKGROUND: Sighing breathing is observed in subjects suffering from anxiety with no apparent organic disease. METHODS: Lung volumes and expiratory flow rates were measured in 12 patients with a sighing pattern of breathing and in 10 normal subjects matched for age, gender, and anthropometric data. In both groups the measurements were made by spirographic and plethysmographic techniques. In normal subjects functional residual capacity (FRC) and residual volume (RV) were measured during normal breathing and again during simulated sighing breathing to exclude technical artifacts resulting from hyperventilation during measurement by the helium closed circuit method. RESULTS: Patients with a sighing pattern of breathing had a normal total lung capacity (TLC) but significantly different partitioning of lung compartments compared with normal subjects. The vital capacity (VC) was lower when measured by both spirographic and plethysmographic methods and RV was higher. The forced expiratory volume in one second (FEV1) was also lower in patients with sighing breathing. The FEV1/VC and the maximal expiratory flow rates at 50% and at 25% of the forced vital capacity (V50 and V25) were normal and similar in both groups. In normal subjects there were no differences in RV when measured during quiet or simulated sighing breathing. CONCLUSIONS: Subjects with sighing breathing have a normal TLC with a higher RV and lower VC than normal subjects. There was no obvious physiological or anatomical explanation for this pattern. PMID- 8211871 TI - Effect of amiloride and saline on nasal mucociliary clearance and potential difference in cystic fibrosis and normal subjects. AB - BACKGROUND: Mucociliary clearance is an important component of pulmonary defence. Maximum clearance is thought to depend on an optimal depth of the sol layer, allowing the most efficient interaction between the cilia and the overlying mucus layer. Sodium absorption, the major ion transport in human airways, is thought to be important in the regulation of the depth of the sol layer. In the airways of patients with cystic fibrosis sodium absorption is increased and mucociliary clearance decreased. Amiloride, a sodium channel blocker, has been shown to improve pulmonary mucociliary clearance in patients with cystic fibrosis. However, its effects on nasal mucociliary clearance in either normal subjects or those with cystic fibrosis are unknown. A study was therefore performed to investigate whether nebulised amiloride improves nasal mucociliary clearance in normal or cystic fibrosis subjects. METHODS: Nasal mucociliary clearance was measured by the saccharin clearance technique in 12 normal subjects and 12 with cystic fibrosis. For the control study measurements were made on two consecutive days and the mean time for each subject averaged. For the drug study measurements were also made on two consecutive days, after administration of nasally nebulised amiloride or placebo (saline) in a double blind manner. Nasal potential difference was measured in eight patients with cystic fibrosis after the administration of amiloride or placebo to assess the efficacy of deposition and duration of action. RESULTS: Baseline values of mucociliary clearance were significantly faster in the normal subjects than in those with cystic fibrosis. In both groups mucociliary clearance was increased after both saline and amiloride, with no significant difference between either treatment. As previously reported, baseline nasal potential difference was significantly more negative in the subjects with cystic fibrosis. Amiloride significantly reduced the potential difference for at least 60 minutes in these subjects. CONCLUSIONS: Nebulised saline significantly improves nasal mucociliary clearance in both normal subjects and those with cystic fibrosis. Amiloride did not appear to exert any additional effects in either group of subjects, despite evidence of its efficacy of deposition. PMID- 8211873 TI - Decrease of histamine induced bronchoconstriction by caffeine in mild asthma. AB - BACKGROUND: While high doses of caffeine may affect pulmonary function and bronchial challenge tests in patients with mild asthma, the effects of lower doses (< or = 5 mg/kg) are less well documented. Specific recommendations exist for withholding theophylline, but not caffeine, before bronchoprovocation and pulmonary function testing. METHODS: To assess the effect of a single oral dose of caffeine (5 mg/kg) on FEV1 and bronchial responsiveness to histamine a double blind, placebo controlled study was performed in eight patients with mild stable asthma. RESULTS: While caffeine had no effect on FEV1, mean (95% confidence interval) log PC20 histamine was significantly higher 150 minutes [caffeine = 0.99 (0.2) mg/ml, placebo = 0.53 (0.29)] and 240 minutes [caffeine = 0.89 (0.24), placebo = 0.44 (0.26)] after administration of caffeine than after placebo. CONCLUSIONS: Caffeine should be excluded from the diet for a period of more than four hours before bronchial provocation testing. The exact length of time for which it must be excluded requires further study. PMID- 8211872 TI - Comparison of fluticasone propionate with beclomethasone dipropionate in moderate to severe asthma treated for one year. International Study Group. AB - BACKGROUND: High dose inhaled glucocorticosteroids are increasingly used in the management of patients with moderate to severe asthma. Although effective, they may cause systemic side effects. Fluticasone propionate is a topically active inhaled glucocorticosteroid which has few systemic effects at high doses. METHODS: Fluticasone propionate, 1.5 mg per day, was compared with beclomethasone dipropionate at the same dose for one year in patients with symptomatic moderate to severe asthma; 142 patients received fluticasone propionate and 132 received beclomethasone dipropionate. The study was multicentre, double blind and of a parallel design. For the first three months patients attended the clinic every four weeks and completed daily diary cards. For the next nine months they were only seen at three monthly intervals in the clinic. RESULTS: During the first three months diary card peak expiratory flow (PEF) rate and lung function measurements in the clinic showed significantly greater improvement in patients receiving fluticasone propionate (difference in morning PEF 15 l/min (95% CI 6 to 25)), and these differences were apparent at the end of the first week. The improved lung function was maintained throughout the 12 month period and the number of severe exacerbations in patients receiving fluticasone propionate was reduced by 8% compared with those receiving beclomethasone dipropionate. No significant differences between the two groups were observed in morning plasma cortisol levels, urinary free cortisol levels, or response to synthetic ACTH stimulation. In addition, both the rates of withdrawal and of adverse events were low, and there were fewer exacerbations of asthma with fluticasone propionate than beclomethasone dipropionate. CONCLUSIONS: This study shows that fluticasone propionate in a daily dose of 1.5 mg results in a significantly greater increase in PEF and asthma control than the same dose of beclomethasone dipropionate, with no increase in systemic or other side effects. PMID- 8211874 TI - Predicting patient attitudes to asthma medication. AB - BACKGROUND: Studies of patient attitudes to asthma and its control have focused on crisis action, and little attention has been paid to attitudes to regular preventive medication. It is not clear whether attitudes to regular medication are related to the degree of distress or interference with life perceived by patients as being caused by their asthma. For this reason this study examined how far dislike of medication related to dislike of other aspects of interference of asthma with daily life. METHODS: Three hundred and ninety one patients were surveyed with a questionnaire which assessed their dislike of the interference of asthma with their physical, social, and emotional functioning, together with dislike of regular asthma medication. A response was received from 320 patients (82%). RESULTS: Four attitude clusters were identified. Recorded in descending factor order, these were (1) dislike of asthma medication, (2) dislike of disability, (3) dislike of public life interference, and (4) dislike of social and emotional interference. The attitude clusters were not related: in particular, dislike of asthma medication could not be predicted from other dislikes, or from asthma best function ratio (ratio of best recorded peak expiratory flow rate in the previous year to predicted value), age, or sex. The most significant predictors of the patients' dislike of taking their own inhaled steroid were (1) dislike of using bronchodilator, (2) dislike of steroids generally, and (3) dislike of taking medicine every day. CONCLUSIONS: Patient attitudes to regular asthma medication are not related to general anxieties and dislikes about asthma, nor to the potential for asthma control as judged by the best function ratio. Patients were not always consistent in their attitude to inhaled steroids in general, nor to their own named inhaled steroid in particular. A general cluster of antimedication attitudes existed, independent of whether the medication was for prophylaxis or relief. Attitudes to asthma medication may be helpful in predicting patient behaviour. PMID- 8211875 TI - Phospholipid content of bronchoalveolar lavage fluid in granite workers with silicosis in Quebec. AB - BACKGROUND: Some of the prominent features of silicosis are hyperplasia and hypertrophy of epithelial type II cells, which in experimental animals are often accompanied by accumulation of phospholipids in the lung. METHODS: The total phospholipid content of lung lavage fluid and its composition in 28 granite stone cutters with long term exposure to silica dust (23 with radiological silicosis) was compared with that of lavage fluid in 15 normal volunteers, 15 patients with untreated idiopathic pulmonary fibrosis, and 19 patients with untreated stage 2 or 3 sarcoidosis. All lavage fluid was obtained at the time of first pulmonary investigation, which also included lung function tests. RESULTS: In the normal subjects total phospholipid content was 1.13 (0.16) micrograms phosphorus/ml of lung lavage, in the patients with idiopathic pulmonary fibrosis 0.52 (0.07) microgram/ml (p < 0.05), and in the patients with sarcoidosis 1.02 (0.20) microgram/ml composition being in the range reported in humans. In the patients with silicosis total phospholipid content was significantly decreased to an average of 0.46 (0.08) microgram/ml compared with the findings in normal subjects and patients with sarcoidosis. Within the group exposed to silica changes in total phospholipid content did not correlate with the severity of the radiographic disease, changes in lung function, the cellularity of lung lavage fluid, or hyaluronate concentrations. The secretory capacity of rat epithelial type II cells was not significantly different when cultured with bronchoalveolar lavage fluid from all four groups of subjects. CONCLUSIONS: Total phospholipid content in lung lavage fluid was significantly reduced in granite workers with radiological evidence of lung disease, but showed no correlation with radiological or functional markers of disease severity. PMID- 8211877 TI - Pulmonary rehabilitation in chronic respiratory insufficiency. 1. Pulmonary rehabilitation in perspective: historical roots, present status, and future projections. PMID- 8211878 TI - Standardisation of gas mixtures for estimating carbon monoxide transfer factor. AB - BACKGROUND: The American Thoracic Society recommends that the inspired concentration used for the estimation of carbon monoxide transfer factor (TLCO) mixture should be 0.25-0.35% carbon monoxide, 10-14% helium, 17-21% oxygen, balance nitrogen. Inspired oxygen influences alveolar oxygen and hence carbon monoxide uptake, such that transfer factor increases by 0.35% per mm Hg decrease in alveolar oxygen. To aid in the standardisation of TLCO either a known inspired oxygen concentration should be used, or TLCO should be corrected to a standard inspired oxygen concentration. The range of gas mixtures used in practice and the implications for cost and accuracy have been investigated. METHODS: A questionnaire was sent to 185 respiratory units in the UK requesting information on (1) the method used to estimate TLCO, (2) the manufacturer of the equipment, (3) the mixture used, (4) whether "medical quality" gas was ordered, and (5) the level of satisfaction with supplier service. RESULTS: Replies were received from 106 units. Most used the single breath breath holding method for which 17 different test mixtures were ordered. One unit also used the single breath exhalation method. Inspired oxygen ranged from 17.94% to 25%, giving a wide variation in alveolar oxygen and hence TLCO. Forty seven units ordered a specific inspired oxygen, the rest ordering "air" as balance. The cost per litre of gas varied greatly, with the mixture 14% helium, 0.28% carbon monoxide, balance air (17.9% oxygen) and 10% helium, 0.28% carbon monoxide, balance air (18.8% oxygen) being cheapest to produce. Ordering a specific inspired oxygen concentration increased the cost. Large cylinders of gas were cheaper for the same mixture. The mixture for the exhalation method was the most expensive. Sixty seven units ordered "medical quality" gas and six assumed this was supplied. Twenty nine (27%) were dissatisfied with their supplier due to (1) poor service, (2) long delivery times, (3) costs, or (4) wrongly labelled cylinders. CONCLUSIONS: It is recommended that two mixtures be available: (a) 14% helium, 0.28% carbon monoxide, balance air for a helium analyser reading up to 15%, and (b) 10% helium, 0.28% carbon monoxide, balance air for lower reading helium analysers. The mixture should be produced under a medical product licence. The advantage of the single exhalation method for routine clinical use needs to be investigated in view of the higher cost of the mixture. PMID- 8211879 TI - Tracheal paraganglioma. AB - The trachea is an unusual site for paragangliomas, only four cases having been documented previously. A fifth case is presented here, together with immunohistochemical evidence that the tumour is biologically benign. PMID- 8211876 TI - Cytokines. 3. Cytokines in asthma. PMID- 8211881 TI - Upper zone cystic lung disease in HIV related Pneumocystis carinii pneumonia. PMID- 8211880 TI - Pleural effusions associated with pancreaticopleural fistula. AB - Two cases of pancreaticopleural fistula are reported. The delay in diagnosis and extensive investigations performed highlight the need for pleural fluid amylase estimation at an early stage. PMID- 8211882 TI - Chlamydia pneumoniae. PMID- 8211883 TI - Regular inhaled beta agonist in asthma: effects on exacerbations and lung function. PMID- 8211884 TI - Respiratory symptoms questionnaire for asthma epidemiology: validity and reproducibility. PMID- 8211885 TI - Pharmacokinetics, thrombogenicity and safety of a double-treated prothrombin complex concentrate. AB - The pharmacokinetic profile, the thrombogenicity and the virus safety of Preconativ, a PCC subjected both to virus removal procedure and dry-heat treatment were studied. Preconativ is produced from plasma pool, negative both for HBsAg and for antibodies to HIV. To further reduce the risk of virus transmission, the manufacturing process includes hydrophobic gel chromatography and dry-heat treatment at +68 degrees C for 48 hours. Nine patients with hemophilia B participated in a single dose, pharmacokinetic study. The decay curves of factor IX clotting activity were evaluated by model-independent methods. The Clearance and the Mean Residence Time were very similar to those previously reported for untreated PCC. The Volume of Distribution Area and In Vivo Recovery resulted inversely correlated and respectively larger and smaller than those of untreated PCC. A slight fall in platelet count and Antithrombin III level and an increase of Beta-Thromboglobulin and Fibrinopeptide A concentration were found, indicating a clear-cut activation of the coagulation process during the first hours following Preconativ administration. Seven patients (2 of the ones enrolled in the pharmacokinetic study) were completely fulfilling the SSC ISTH criteria for virus safety prospective study. The follow up of these patients did not show any transaminases elevation or seroconversion against HBV, HCV or HIV. These findings did not change over a 3-5 year follow up in 3 out of 7 patients, repeatedly infused with Preconativ. PMID- 8211886 TI - Leukotriene formation by peripheral monocytes in contact-activated human blood. AB - Contact activation of the intrinsic coagulation cascade in whole human blood in vitro has previously been demonstrated to trigger release of leukotrienes (LT) into serum samples. In our present study we intended to identify the cellular origin of the activated 5-lipoxygenase pathway leading to LT formation under these experimental conditions. Therefore, whole human blood samples incubated for 60 min in vitro were supplemented with Percoll-isolated, 5-lipoxygenase-carrying, autologous blood cells. Surprisingly, exogenously added polymorphonuclear neutrophils (PMN, 5 x 10(6) or 15 x 10(6)/ml) capable of producing cysteinyl-LT in response to ionophore A23187 (1 microM) stimulation, had no effect neither on immunoreactive cysteinyl-LT nor on thromboxane (TX) B2 formation. However, exogenously added mononuclear cells (MNC, 5 x 10(6) or 15 x 10(6)/ml) led to a cell number-dependent increase in cysteinyl-LT generation as did supplementation with peripheral monocytes (PM, 5 x 10(5) or 15 x 10(5)/ml). While MNC enhanced the TXB2 production, PM had no such effect. Incubation of PM (5 x 10(5) or 15 x 10(5)/ml) in recalcified platelet-rich plasma (PRP) induced a cysteinyl-LT formation comparable to that in whole human blood. In contrast to the TXB2 generation, the cysteinyl-LT formation appears to be largely independent from thrombin, since recombinant hirudin (HBW 023, 2 microM), a specific thrombin inhibitor, had no significant effect on the cysteinyl-LT production but nearly completely abolished the TXB2 formation. By reverse phase HPLC the immunoreactive cysteinyl-LT were shown to consist of a mixture of LTC4, LTD4 and LTE4, with LTC4 being the predominant metabolite in all samples studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8211887 TI - Spectrophotometric evaluation of the adhesion of blood platelets to collagen and microfibrils. AB - We present an easy method in which the adhesion of platelets to collagen or to MFs was measured in a spectrophotometer, after an incubation of hypercitrated platelet rich plasma (PRP), or of a platelet suspension, with an inducer, followed by the filtration of non adhering platelets through translucent Isopore membrane filters (pore diameter = 5 microns). The adhering platelets, which are retained on the filter, were stained by Coomassie blue to quantify the adhesion by the simple reading of the O.D. 580 nm of the stained platelets which appear as a blue spot on the translucent membranes. PMID- 8211888 TI - Effect of prostaglandin (PG) E1 and its initial metabolites on neutrophil-induced inhibition of human platelet aggregation. AB - We have investigated the effects of PGE1, 15-keto-PGE1, 15-keto-13,14-dihydro PGE1 and 13,14-dihydro-PGE1 on inhibition of human platelet aggregation by rat peritoneal neutrophils (RPN) and human polymorphonuclear neutrophils (PMN). Both RPN and PMN are known to synthesize nitric oxide (NO). In the presence of a threshold concentration of RPN or PMN the inhibitory effects of PGE1 and 13,14 dihydro-PGE1 on thrombin- or collagen-induced platelet aggregation were significantly increased as compared to the absence of cells, while 15-keto-PGE1 and 15-keto-13,14-dihydro-PGE1 were inactive. Oxyhemoglobin (oxy-Hb) abolished the synergistic effect of RPN and either PGE1 or 13,14-dihydro-PGE1 on thrombin induced platelet aggregation, but under the experimental conditions used had much less effect on inhibition of collagen-induced aggregation. Potentiation of the antiaggregatory effect of PGE1 and 13,14-dihydro-PGE1 by NO might contribute to the therapeutic efficacy of exogenous PGE1. This view is supported by the fact that plasma levels of PGE1 and its active metabolite in patients receiving infusions of PGE1 for treatment of peripheral arterial occlusive disease are in the order of magnitude acting synergistically with neutrophil-derived NO, while direct inhibition of platelet aggregation requires considerably higher concentrations of PGE1 and 13,14-dihydro-PGE1. PMID- 8211889 TI - Increased generation of reactive oxygen species in mononuclear blood cells from hypercholesterolemic patients. PMID- 8211890 TI - Monomerization of fragment DD by destabilase from the medicinal leech does not alter the N-terminal sequence of the gamma-chain. PMID- 8211891 TI - The influence of fluid dynamics upon adhesion of ADP-stimulated human platelets to endothelial cells. PMID- 8211892 TI - [Memento mori. A theme series on medical philosophy and history of ideas]. PMID- 8211893 TI - [More stroke units]. PMID- 8211894 TI - [Donor insemination--openess or secretiveness?]. PMID- 8211895 TI - [Methotrexate. Efficient, but not without hazards in rheumatoid arthritis]. PMID- 8211896 TI - [There are no diseases, there are only ill persons--about our use of the fibromyalgia concept]. PMID- 8211897 TI - [Fibromyalgia--a relationship between psyche and soma?]. AB - Fibromyalgia is regarded a state of pain that can both be triggered and maintained by a broad spectre of events, ranging from massive psychogenic stress to long-lasting excessive somatic strain. Based on a review of selected studies supported by the Norwegian Medical Research Council, this paper focuses on muscular exercise and related pain, the functional significance of certain neuropeptides, the contribution of the sympathetic nervous system and the psychological aspects of the condition. PMID- 8211898 TI - [Etiological aspects of fibromyalgia]. AB - The etiopathogenesis of primary fibromyalgia still remains an enigma to modern medicine. Several hypotheses have been suggested during the last years, and these are reviewed. PMID- 8211899 TI - [Experiences from a stroke unit in a county hospital]. AB - We review our experience from a stroke unit run as a project in a county hospital serving a population of 95-100,000. The average length of stay in hospital was 33.5 days. The mortality rate was low (10%). 73% of the patients were discharged to their homes, either directly or after a short stay of less than three months in nursing homes. A questionnaire sent to the patients after the end of the project period confirmed that about 70% were living at home 1-15 months after discharge. These findings are in accordance with the results from other stroke units, and support the conclusions of other investigators that treatment in stroke units improves the outcome for patients with acute stroke. We also briefly discuss complications, follow-up after discharge, and the implications for the patients' families. PMID- 8211900 TI - [Pancytopenia during low-dosage methotrexate treatment in patients with rheumatoid arthritis]. AB - Adverse effects are no more common during treatment with low doses of methotrexate than during treatment with conventional anti-rheumatic drugs. Serious events do occur, however, and among the most dangerous is pancytopenia. We describe five patients with this complication. Triggering factors for such adverse events are often interactions with other medication, especially drugs that reduce renal clearance of methotrexate, and also other anti-folate drugs, e.g. trimetoprim. Events that increase the rate of cell formation in the myelopoietic tissue, e.g. infection and haemorrhage, may also increase risk of complications. Use of leukovorin is recommended when bone marrow suppression is suspected. PMID- 8211902 TI - [Past and present--the roots of our modern concept of disease in 19th century clinical practice and science]. AB - Historically speaking, our current clinical conceptions of disease are derived from 19th century science and clinical practice. In the early 19th century, large hospitals with hundreds of patients were erected for the first time. This provided "material" to which the physicians could apply their new diagnostic techniques and tools: percussion and auscultation, aided by the newly invented stethoscope. Eventually, what was found at the bedside was systematically compared with what was discovered on the autopsy table. This clinical research programme was challenged by, though later combined with, the experimental physiology and "laboratory medicine" of men like Francois Magendie and Claude Bernard. Their strong programme to introduce pure science, i.e. physics and chemistry, into medicine was paralleled by further developments in the old solidistic pathological tradition; an improved microscope and new techniques for preparing tissues for the microscope, led to the development of truly microscopic anatomy and cellular pathology. The idea that disease may be caused by microscopic living organisms was tested by means of strict experimental, scientific methods by men such as Louis Pasteur and Robert Koch; and our current conception of infectious disease is still very similar to that of the first microbiologists of the 1870s and 80s. The last 19th century root of our modern conceptions of disease discussed in the present essay is the visualization of the interior of the body--indeed, the visualization of disease--by X-rays. PMID- 8211901 TI - [Hearing loss after erythromycin therapy]. AB - We describe the case of a patient who developed bilateral loss of hearing during intravenous treatment with erythromycin. Predisposing factors may have been reduced renal and hepatic function and treatment with diuretics and aminoglycosides. Recovery was late, but hearing was probably restored to almost pre-treatment level. Patients receiving high doses of erythromycin should, as a routine, be questioned about hearing loss and tinnitus. PMID- 8211903 TI - [Clinical decisions in a philosophical perspective]. AB - Medicine is both a scientific and a humanistic discipline. The foundation for clinical decisions has four components (two scientific and two humanistic). 1) The biological component (reasoning based on biological theory). Biological thinking is currently being revolutionised, partly through the development of systems theory. 2) The empirical component (reasoning based on experience from earlier patients), which comprises both uncontrolled and controlled experience. 3) The empathic-hermeneutic component (reasoning based on an understanding of the patient as a fellow human being). Empathy requires hermeneutic knowledge which can be acquired through personal experience and by qualitative research. 4) The ethical component which comprises both utilitarian and deontological considerations. PMID- 8211904 TI - [Therapeutic possibilities in acute cerebral infarction]. AB - Drug treatment of acute ischemic stroke may be divided into four categories: antithrombotic treatment, thrombolytic treatment, neuronal protection, and other forms of treatment. Until now, no drug treatment has been properly documented as effective. However, several treatment programmes are currently being evaluated. Maintenance of the cerebral perfusion pressure and early mobilisation are important factors when treating acute stroke. PMID- 8211905 TI - [Familial relations in connection with donor insemination. Psychological effects of secretiveness]. AB - In Norway approximately 150 children are born every year as a result of artificial insemination. In 1987 an Act was passed regulating this practice. Hospital gynaecologists are given the authority to implement this Act, and the responsibility for doing so. With the current practice of artificial insemination, two types of secrets evolve: The anonymity of the donor, as required by law, will prevent the child from ever identifying its biological father. The secrecy of conception, as recommended by experienced gynaecologists as the best method of protecting the child and the parents, will continuously present the family with unresolved questions that may create problems within the family. It is assumed that it would present an undue burden on the child not to be able to identify its biological father. As a family psychiatrist the author has discussed the secrecy issue with nine couples with children conceived by artificial insemination using donor semen, and another eight couples that were offered this treatment. A common denominator for these couples turned out to be the problem of living their entire life not knowing the origin of their child. Most of the couples are afraid that the secret could be divulged during a family quarrel. Invisible alliances could develop between members of the family. In the long run, honesty about the conception reduces the mental strain on the family. Family therapists will generally advise against secrecy in these matters and will help parents choosing alternative ways of coping with the problems. PMID- 8211906 TI - [Diagnostic rationalism. Views of general practitioners on fibromyalgia]. AB - Clinical practice is characterized by having to make numerous important decisions, including the diagnosis. In this study, general practitioners were asked to agree or to disagree with statements of fibromyalgia. The main purpose was to test the usefulness of two well-known models for decision-making when studying diagnosis in cases of uncertainty and scepticism. The results show that the models are inadequate to explain the decisions. PMID- 8211908 TI - [Are we honest in the waiting list guarantee?]. PMID- 8211907 TI - [What do Norwegians know about sexually transmitted diseases? Results from a survey on Norwegians' knowledge about sexually transmitted diseases]. AB - This paper reports on knowledge about sexually transmitted diseases in Norwegian adults. The sample (572 males and 601 females) was representative of Norwegians aged 15 and above. Data were collected by means of personal interviews and self completed questionnaires. Out of ten respondents, seven did not know that sexually diseases are not transmitted via toilet seats; six that syphilis is not the most prevalent of the sexually transmitted diseases in Norway; five that both males and females can be infected by chlamydia; four that contraceptive pills do not protect against chlamydia infection; three that condoms protect against all sexually transmitted diseases; and two that condoms protect against gonorrhoea and that females infected by sexually transmitted diseases run higher risk of infertility. Knowledge about sexually transmitted diseases was lowest in the youngest and oldest age groups, and increased monotonously with increased education. PMID- 8211909 TI - [Pro-ANF--a new diagnostic aid in heart failure]. PMID- 8211910 TI - [Surfactant therapy of neonatal respiratory distress syndrome]. PMID- 8211911 TI - [Ethics as a tradition is worth to be preserved. Considerations on medical ethics]. PMID- 8211912 TI - [Is the study veterinary medicine student-unfriendly?]. PMID- 8211913 TI - [Post-academic instruction in veterinary education]. PMID- 8211914 TI - [A new curriculum veterinary education: on the road to the 21st century]. PMID- 8211915 TI - [Back in Utrecht after 11 years]. PMID- 8211916 TI - [Specialization in veterinary medicine]. PMID- 8211917 TI - [Observations on the future of our profession]. PMID- 8211918 TI - [Diarrhea in calves]. PMID- 8211919 TI - ['Yes, yes, we confirmed everything with tests'...]. PMID- 8211920 TI - [Toxocara ova in parks and sand-boxes in the city of Utrecht]. AB - An investigation was carried out for the presence of Toxocara spp. eggs in public parks and children's sand-boxes in the city of Utrecht. The pollution of parks with the eggs of the dog's ascarid Toxocara canis is comparable with reports from other European cities. The eggs of Toxocara cati were found in small numbers only. Interestingly there was no difference between parks with or without formal exclusion of dogs. Most sand-boxes are polluted with the eggs of the ascarid of cats T. cati. Incidentally eggs of T. canis were found. Sand-boxes which were obviously kept clean or could be closed contained lower numbers of eggs. As children playing in sand-boxes have far more chances to contaminate themselves with Toxocara eggs than when playing in parks or on playgrounds, the question arises if not T. cati eggs constitute a greater menace, at least in urban areas, to public health than T. canis eggs. PMID- 8211921 TI - [Status epilepticus or cluster epilepsy?]. AB - Cluster seizures and status epilepticus may look similar but are to be treated differently. They have a totally different prognosis. During cluster seizures the daily dose of anti-convulsants is temporarily increased. Status epilepticus is treated with intravenous or rectal administration of diazepam combined with intramuscular or intravenous administration of phenobarbital. Two dogs with atypical status epilepticus are described. PMID- 8211922 TI - [Genetic modification of animals, is it allowable?]. PMID- 8211923 TI - [White exanthema in fishes]. PMID- 8211924 TI - Development of the surgical stapling device. AB - Most surgeons who use staplers today attribute their invention to researchers who worked during the mid-fifties in the Soviet Union. While the modern staplers are derivates of those instruments, it also needs to be emphasized that they were preceded by stapling devices which were used extensively as early as the first decade of this century. The early history of surgical staplers is full of imaginative new ideas and technical solutions clearly identified as the instruments we use today were developed. The great men in Hungary and Germany who invented the early staplers should be remembered for their accomplishments. PMID- 8211925 TI - Reduction of the left-ventricular outflow-tract obstruction by aortoventriculoplasty--long-term results of 96 patients. AB - The aortoventriculoplasty (AVP) is an established surgical procedure for enlargement of different types of congenital and acquired obstruction of the left ventricular outflow tract (LVOTO), especially with narrowing of the aortic valvular and subvalvular segment. Between 1974 and 1992, 96 patients underwent AVP. There were 32 female and 64 male patients, aged 3 to 32 years (mean 11.2 +/- 2.7 years) at operation. Indications for the procedure were as follows: 1. narrowing of the aortic annulus (19 patients), 2. multi-level stenosis (26 patients), 3. "outgrown"-prosthesis (8 patients), 4. recurrent hypertrophic obstructive cardiomyopathy (HOCM) (5 patients), and 5. subaortic stenosis of different origins (38 patients; out of these 19 patients had a "tunnel-like" stenosis, 7 of them with a "Shone-complex"). Seventy-six patients had previous operations at different levels of the left-ventricular tract. The mean preoperative peak transvalvular gradient was 88 +/- 27 mmHg (range 50-160 mmHg) and could be reduced by AVP to 14 +/- 13 mmHg. The early mortality was 8.3% (8/96). Among the last 58 patients there were no deaths. Three patients underwent subsequent reoperations: one for ascending aortic aneurysm, one for right ventricular outflow tract obstruction (RVOTO), and one for "outgrown" prosthesis. Three patients required pacemaker implantation for a permanent a-v block, 71 of 96 patients had sinus rhythm postoperatively. The long-term results are similar to those of standard aortic valve replacement in childhood and adolescents. The advantages and disadvantages of the AVP in comparison to the other alternative surgical methods for relief of LVOTO are discussed. PMID- 8211926 TI - Increased resistance against shortening in myocardium from recipient hearts of 7 patients transplanted for dilated cardiomyopathy. AB - The contractile behaviour of demembranized atrial and ventricular myocardium of 7 patients transplanted for end-stage heart failure (ESHF) was analyzed. Atrial muscle specimens of patients undergoing coronary artery bypass surgery (n = 9) and pig papillary muscle were used as reference preparations (n = 9). Extreme care was taken for dissection and mounting the muscle fibres (0.3 x 6 mm) in order to keep the passive series compliance small. Calcium sensitivity, cross bridge cycling rate (estimated by the force-clamping technique and calculation of the shortening velocity at zero load [Vmax]) and isometric force development were measured. Analysis on light- and electronmicroscopic level was carried out. RESULTS: 1) Calcium sensitivity was not altered in ESHF patients; 2) the velocity of the force generating process (cross-bridge cycling rate) was normal in ventricular and reduced in atrial ESHF myocardium, 3) maximum isometric force development was reduced in ventricular, but not in atrial myocardium of ESHF patients, and 4) Vmax was significantly reduced in ventricular and atrial ESHF myocardium (p < 0.0001). Perimysial and endomysial fibrosis was present in ventricular, not in atrial myocardium of ESHF patients. CONCLUSION: A normal cross-bridge cycling rate in left-ventricular ESHF myocardium combined with a decreased capability of muscle shortening indicates the presence of a resistance against shortening localized either on the cross-bridge level or/and due to intra and pericellular fibrosis. Left-ventricular contractile dysfunction in patients with end-stage heart failure may be related to a normal contractile apparatus contracting within an abnormal intracellular or interstitial environment. PMID- 8211927 TI - Implantation of the automatic implantable cardioverter defibrillator for coronary artery disease--surgical experience in 185 patients. AB - The results in 185 patients with coronary artery disease undergoing implantation of an automatic implantable cardioverter defibrillator (AICD) were reviewed with regard to the operative technique applied and problems observed. In 123 patients (group I) only AICD implantation was performed. Ninety patients were operated through sternotomy or thoracotomy while in 33 patients an endovenous/subcutaneous technique was used. Sixty-two patients (group II) underwent simultaneous coronary artery bypass grafting (CABG) and AICD implantation by median sternotomy. Perioperative mortality was 2.4% in group I with one fatality in the subgroup of endevenous/AICD placements and 11.3% in group II (p < 0.01). Overall infectious complications were low with 2 removals in group I and 1 in group II; however, no infections were observed after endovenous system implantation. It is concluded that the operative mortality rate of a combined approach is significantly higher, when compared to isolated AICD placement. However, the greater risk of the former cohort is mainly due to the impaired ventricular performance. Further investigations will have to prove whether a two-step approach using the endovenous technique in patients with a need for AICD and CABG will reduce the operative mortality. PMID- 8211928 TI - Acute renal failure after coronary surgery--a study of incidence and risk factors in 2009 consecutive patients. AB - To obtain a model for the prediction of acute renal failure (ARF) after coronary surgery, 2009 consecutive patients were investigated. ARF was defined as a peak postoperative serum creatinine value exceeding the preoperative value by 50% or more or a need for dialysis. A postoperative increase in serum creatinine of less than 50% was associated with an early mortality (< or = 30 days postop.) of 0.4%. Sixteen per cent of the patients increased their serum creatinine by more than 50% and in this group there was a mortality of 1.3%. Twenty-five patients (1.2%) required postoperative haemodialysis because of ARF and of these 11 (44%) died early, whereas another 7 patients with chronic renal failure, requiring both pre- and postoperative haemodialysis, all survived. Peak postoperative serum creatinine and changes from the preoperative value were analyzed and related to clinical variables. Multivariate analysis indicated that high preoperative serum creatinine, high age and postoperative haemodynamic instability were the most important risk factors for developing renal failure. A logistic model including these risk factors versus the probability of developing ARF is presented. PMID- 8211929 TI - Palmar thermometry for intraoperative success control of thoracic sympathectomy. AB - In a pilot study involving six patients, palmar thermometry was used as a non invasive method for intraoperative success control during thoracic sympathectomy. Using commercially available thermo-elements and amplifier modules, a marked increase in temperature could be registered in five patients after the severance of their rami communicants grisei for the hand. This effect was associated with the long-term success of therapy for hyperhidrosis in all five patients. This initial experience demonstrates that palmar thermometry is sensitive enough to measure surgical success intraoperatively. The limit of the thoracic sympathectomy in the cranial direction is indicated intraoperatively and Horner's syndrome is avoided with certainty. PMID- 8211930 TI - Selective video-assisted thoracoscopic sympathectomy. AB - Video-assisted and thermometrically controlled thoracoscopic sympathectomy demonstrates new ways in the treatment of upper-limb hyperhidrosis. An anatomical portrayal of the sympathetic chain is possible as a result of the improved visualization and magnification of the operative area provided by the video-optic technique. The difference in temperature, registered by means of a thermometric sensor in the palm of the hand, indicates that the sympathetic nerves responsible for the hyperhidrotic segments have been severed. The number of postoperative Horner's syndromes will be reduced significantly with this method. Until now, we have successfully treated six thermometrically controlled patients. No recurrences have arisen during an 18 months observation period. Neither intraoperative nor postoperative complications were recorded. One patient complained of increased compensatory sweating of the trunk. Thermometrically controlled thoracoscopic sympathectomy is expected to improve the various forms of treatment available for sympathetic reflex dystrophies in the future. PMID- 8211931 TI - Isolated man-in-the-barrel syndrome following cardiac surgery. AB - A 59-year-old chronically hypertensive patient developed "man-in-the-barrel syndrome" following urgent coronary artery bypass graft surgery (CABG). This syndrome describes a brachial diplegia with intact motor function of the legs. Magnetic resonance imaging confirmed areas of ischaemia consistent with hypoperfusion leading to border-zone infarction between the territories of the anterior and middle cerebral arteries. The patient made a complete functional recovery. PMID- 8211932 TI - A case of coronary stenosis developing after successful aortic valve repair in Cogan's syndrome. AB - Cogan's syndrome has been described as entity of progressive deafness and interstitial keratitis with variable cardiovascular involvement leading to aortic insufficiency or orificial stenosis of coronary or aortic arch vessels. So far, aortic valve replacement either with mechanical or biological prosthesis was favored for correction of the valvular lesion. A patient with primary successful aortic valve repair followed by coronary revascularization for left coronary ostial stenosis occurring after the first operation is presented. PMID- 8211933 TI - A symptomatic papillary fibroelastoma of the left ventricle removed with the aid of transesophageal echocardiography. AB - A papillary fibroelastoma, causing amaurosis fugax and paresis of the right arm, was detected by echocardiography as a free floating mass in the left-ventricular outflow tract. Based on the exact localization of the tumor by intraoperative transesophageal echocardiography the initial indication for ventriculotomy was disregarded and an atraumatic transvalvular approach was chosen. PMID- 8211934 TI - A case of cardiac hydatid cyst localized in the lungs bilaterally and on anterior wall of right ventricle. AB - A 23-year-old man had been coughing with hemoptysis, and had received tuberculostatic medication for four months without any benefit. Upon referral, two-dimensional echocardiography showed a cystic mass located in the anterior right-ventricular wall, without any protrusion into the ventricular cavity. CT examination revealed three cysts in the lung fields bilaterally, additionally a multilocular cystic image in the right-ventricular wall was observed. All components of hydatid cysts in the heart and lungs were removed in the same session by median sternotomy. Extracorporeal bypass was used in this operation. PMID- 8211935 TI - [Familial occurrence of esophageal atresia]. AB - Two siblings with esophageal atresia are reported, and literature data as to familial occurrence and heredity have been reviewed. Until now, only statistical data can be given: the recurrence risk for sibs after one affected child is around 0.5-2% and after two affected children around 20%. The risk for the children of a parent affected by congenital esophageal atresia is estimated at around 3-4%. This is compatible with the recurrence risk of a multifactorial condition in first degree relatives. However, two patients have been described in which the possibility of autosomal dominant transmission has been raised. PMID- 8211936 TI - [Interstitial pneumonia in childhood: a clinical picture different from COPD]. AB - Chronic respiratory symptoms in children are often caused by asthma. In this paper we present two children with chronic respiratory symptoms, which we first attributed to asthma. Since the presence of symptoms were not in agreement with asthma and because the children did not respond to asthma therapy, another cause of chronic lung disease was suspected. An open lung biopsy was performed. Histological diagnosis in both patients was an interstitial pneumonia. Differential diagnosis between interstitial pneumonia and asthma can be difficult, however there is a difference in symptomatology between these two diseases. Symptoms which may indicate the presence of another chronic lung disease than asthma are: absence of symptom-free periods, persistence of impaired exercise tolerance, hemoptysis, recurrent auscultation of crackles during symptomatic periods and digital clubbing. PMID- 8211937 TI - [2 children with stridor and a thymus in the posterior mediastinum]. AB - Two infants are described with an inspiratory and expiratory stridor with apnea. X-ray examination showed a mass in the posterior mediastinum. For this reason both infants underwent a diagnostic thoracotomy because detailed study didn't resolve the problem. An aberrant localized thymus was found in both infants. In both infants, however, the complaints persisted after the operation. Both infants needed a second operation to relieve the stridor, which appeared to be due to (primary and secondary) tracheomalacia. This article describes shortly the embryology of the abnormally located thymus. The possibilities to diagnose a posterior mediastinal mass without thoracotomy are also described. Using magnetic resonance imaging (MRI), the posterior located thymus can be diagnosed noninvasively in most cases. The aberrantly positioned thymus should be included in the differential diagnosis of a posterior mediastinal mass, otherwise invasive methods are needed to come to the good diagnosis. PMID- 8211938 TI - [Chronic recurrent abdominal pain in school children]. AB - The diagnostic approach of children with recurrent abdominal pain (RAP) was investigated by means of a standard protocol. The protocol consisted of recently developed laboratory techniques and 'routine' investigations. In addition, all patients were subjected to an extensive psychological investigation. The main results show that in a high percentage (42%) of patients organic abnormalities could be found. Particularly the small bowel seemed to be involved in the pathogenesis of the complaints. Furthermore, gastro-esophageal reflux appeared to be present in as many as 50% of the patients investigated and there might be a relationship with the abdominal pain complaints. Helicobacter pylori did not appear to play an important role in these patients. Comparing the results of the psychologic investigation with a pain-free control group, we did not find clear evidence that psychological factors play a role in the pathogenesis of these patients' complaints. Children with RAP, particularly when complaints exist longer than 6 months, need to be investigated for the presence of organic abnormalities that might provide an explanation for the complaints. PMID- 8211939 TI - [Central venous catheters in newborn infants. Work Group Parenteral Nutrition of the Perinatology Section of the Dutch Pediatric Society]. AB - In this article guidelines regarding the use of indwelling central venous catheters are given. Indications, insertion techniques, possible complications and management are described. Furthermore a survey of the commercially available catheters in the Netherlands is made. PMID- 8211940 TI - [Effect of age of erythrocyte concentration administered to premature infants: a retrospective study]. AB - Traditionally fresh red blood cells (RBCs, age less than 10 days) are used for neonatal transfusion. Retrospectively we studied the influence of the age (range 2-34 days, divided into age groups 1-7, 8-14, 15-21, 22-28, 29-35 days) of RBCs on hemoglobin, pH, bicarbonate, and potassium after administration of a small amount of packed RBC (10-15 ml/kg). We reviewed the hospital records of 58 preterm infants (mean birth weight 1316 +/- 543 g, mean gestational age 30 6/7 +/ 3 weeks) who received 201 transfusions (mean of 3.5 RBC transfusions per infant; range 1-22). Following transfusion there was a significant increase in hemoglobin in all age groups. No significant change occurred in pH, bicarbonate or potassium. We conclude that RBCs used for neonatal transfusions do not need to be fresh. Multiple donor exposure of neonates can be limited by splitting blood of a single donor into small portions and using them up to 35 days. PMID- 8211941 TI - [Immunoglobulin levels in premature infants on a neonatology unit]. AB - Serum IgG, IgA and IgM concentrations of premature infants, 21 boys and 17 girls, gestational age 29.8 +/- 2.5 weeks, birth weight 1243 +/- 378 gram, were measured during the first weeks post partum. At birth, IgG concentrations of newborn infants correlate with gestational age. Subsequently a gradual decline of IgG concentrations occurs. Infants of 25-29 weeks gestational age appeared to have significantly lower IgG concentrations if compared to infants of 29-32 weeks gestational age. IgA concentrations remained below the detection limit during the period covered by this study, whereas serum IgM concentrations showed a gradual increase. Significantly more infants from the group with IgG < 400 mg/dl, measured at the first day of life, had infections if compared to the group with IgG > 400 mg/dl. Exchange transfusions and administration of fresh frozen plasma (FFP) resulted in a rise of immunoglobulin concentrations, whereas administration of packed cells (PC's) and pasteurised plasma protein solution (GPO) did not. PMID- 8211942 TI - [Sudden and unexpected death in a young child. 'Crib death' in an older child]. AB - The history of a toddler who died suddenly and unexpectedly is given. The day before the child suffered from gastro-enteritis. Postmortem examination revealed hypoglycemia. Urine-analysis was highly suspective of a medium chain acyl-CoA dehydrogenase deficiency. This diagnosis was confirmed by further family investigation, including identification of the common point mutation in this disorder. The consequence of such a deficiency is discussed. PMID- 8211943 TI - [Dysmaturity as symptom of the ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome]. AB - Low birthweight as a symptom of the ectrodactyly ectodermal dysplasia clefting (EEC) syndrome is described before by Anneren. By presenting two patients (father and son) we give a brief review of the major and minor symptoms. We would like to add low birthweight as a minor symptom. PMID- 8211944 TI - Behavior of embryonic chick heart cells in culture. 1. Cellular responses to insulin-transferrin-selenium. AB - Muscle cell-enriched primary cell cultures were prepared from 8-day embryonic chick heart ventricles (74% of these cells showed positive staining with anti cardiac myosin antibody). To determine if ITS (a commercial mixture of insulin, transferrin, and selenium) affects these cardiac muscle cells, immunostaining and autoradiography were performed to determine the Muscle Cell Labeling Index (MLI). MLI represents the proportion of cardiac myosin-positive cells that specifically incorporated [3H]thymidine. The MLI for ITS-treated cells was 52%. Controls in Serum-free Nutrient Medium (SFNM) had a MLI of 27%. Combinations of growth signals also were tested. Whereas 5% Fetal Bovine Serum (FBS) was optimal for stimulation of [3H]thymidine incorporation, 10 and 20% FBS elicited an inhibitory effect. Addition of ITS enhanced the stimulatory effect of FBS and relieved some of the inhibitory effect. TGF-beta also was shown to have inhibitory effect on [3H]thymidine incorporation in these heart cells, but the inhibitory effect was not seen when it was added with ITS. Staining with anti-cardiac myosin antibody revealed that when the cells were cultured with ITS for 6 or 10 days, the percentages of muscle cells were 65 and 59%, whereas the percentages of muscle cells of controls in SFNM dropped to 44 and 31% respectively. Additional experiments showed that cell number increased in the presence of 5% FBS. In contrast, although ITS stimulated DNA synthesis, it did not immediately stimulate complete cell division. The percentage of muscle cells remained around 74% in the presence of 5% FBS, whereas it fell slightly (to 65%) in SFNM. This study showed that cardiac muscle cells from 8-day embryos in culture were responsive to ITS, FBS and TGF-beta and that ITS may be permissive for continued expression of differentiation of embryonic cardiac muscle cells. PMID- 8211945 TI - Nature, origin and fates of membranous lamellae in the lung of the neonate rat. AB - This study explores the basic nature and formation of lamellar accumulations in the vertebrate lung, and the problematical interrelationship of the lamellae with mitochondria. Autolysosomes are a constant feature of the type II alveolar pneumonocyte of the 2-day-old rat. They are characterized by a single boundary membrane, enclosing a heterogeneous collection of vesicles and membraneous lamellae. The autolysosomes result from repeated episodes of glycogen catabolism, and eventually transform into osmiophilic lamellated bodies. Membranous lamellae within autolysosomes and lamellated bodies represent isolating membranes of cellular autophagy, emptied of their digested contents. Proliferated isolating membranes themselves undergo lysis, providing recycled constituents for the differentiating or dividing cell. Mitochondria of the type II alveolar cell often display invaginations occupied by membranous masses; these masses are demonstrated by high magnification electron micrographs to be continuous with and derived from lamellated bodies, a new finding. Inner mitochondrial membranes lining the invaginations are thinned and crista-free. It is concluded that undergraded or partially lysed isolating membranes follow either of two cellular pathways: they may be eliminated from the cell into the alveolar cavity, or may fill mitochondrial indentations. PMID- 8211946 TI - Diurnal variation in adrenal gland freshweight due to vascular damming: a possible role in corticosterone storage. AB - Previous in vitro studies have disclosed the existence of a diurnal variation in adrenal gland freshweight in the minimally stressed rat (inactive phase freshweight > active phase freshweight). In the present study this active/inactive phase difference in adrenal weight was examined using light microscopy, transmission electron microscopy (TEM) and backscattered scanning electron microscopy (BSEM). Morphological and stereological examination of the resultant micrographs has shown a significant increase in gland cross-sectional width in the active phase, localised to the zona fasciculata/reticularis region of the cortex. However, TEM examination of cells from this region, comparing volume and surface densities from active and inactive phase glands, has not provided evidence of a diurnal variation in cell size. Analysis of the BSEM investigation of vascular, cellular and interstitial compartments of the glands confirmed the absence of variation in the cellular compartment but showed a diurnal variation in the vascular compartment of the zona fasciculata/reticularis. The circadian related changes in vascular volume density begin at the cortico-medullary border where greatest difference is observed between the active and inactive phases. This difference continues throughout the zona fasciculata/reticularis decreasing in size as it approaches the zona glomerulosa region. These findings are explained in terms of the existence of a cortico-medullary vascular dam that is a possible contributor to the rapid steroidogenic response seen on initial stimulation of the gland by adrenocorticotrophic hormone (ACTH). PMID- 8211947 TI - Increase of the bursal follicular medullary compartment in chicks intracloacally inoculated with Bordetella pertussis. AB - The cloacal bursa is a primary lymphoid organ responsible for the maturation of B lymphocytes. It has been suggested that the bursa may also play a peripheral role when antigens are inoculated by cloacal route. Qualitative and quantitative structural modifications in the bursa from chicks inoculated with Bordetella pertussis by the cloacal route were investigated. Observations indicated that the relative bursal growth as well as the volume fraction and the mitotic index of the follicular medulla from experimental bursae are significantly greater than those of the controls. Macrophages which have phagocytized bacteria, and a gradual relative increase of the RER of lymphoblasts, were other structural modifications found exclusively in the follicular medulla. The observations suggest that the bursal follicular cortex and medulla act as autonomous histophysiological compartments, the latter being responsible for an antigenic stimulation when Bordetella pertussis is intracloacally inoculated in chicks. PMID- 8211948 TI - Cytometric study of the female Syrian hamster gallbladder epithelium following sex steroid administration. AB - This report is a cytometric study of the female Syrian hamster gallbladder epithelium following 1-, 2-, and 3-month administration of female sex steroids. Nulliparous, multiparous, young, old and pregnant hamsters were used in this study. A 1 month treatment with estrogen alone significantly increases the nuclear volume of the gallbladder epithelial cells, while E + P treatment significantly affects the nuclear volume only after a 2 month treatment. On the other hand, E + P and P treatments significantly increase the cell volumes as compared to the E-treated groups, this effect is most striking following the 1 month period. Prolonged sex steroid treatment (2 and 3 month) does not appear to influence the gallbladder epithelial cell and nuclear volumes as dramatically as that observed following the 1 month treatment. The nulliparous, progesterone treated hamsters appear to have a greater cytoplasmic volume than the multiparous group and this is substantiated by the bulging apices and the luminal cellular excrescences observed with scanning and transmission electron microscopy. These observations are similar to those reported in ovariectomized hamsters (Gilloteaux et al., 1992). Further, the gallbladder epithelial cells and nuclei of the older female hamsters demonstrate an accentuated response to a 1 month sex steroid treatment as compared to the younger hamsters for the same treatment duration. These results enable us to hypothesize that changes induced by a short term sex steroid treatment participate in the gallstone nucleation process, while longer duration of the treatments contribute to progressive enlargement and accumulation of gallbladder calculi. PMID- 8211949 TI - Fine structure of nuptial pad surface of male ranid frogs. AB - The nuptial pad, a cutaneous secondary sexual characteristic, developed on the ventrolateral aspect of the first digit (the thumb) of the male ranid frogs was observed. Under scanning electron microscopy, numerous small elevations were observed rising above the pad's surface; they were rounded in Rana brevipoda porosa and R. rugosa, conical in R. nigromaculata, and rather tall and gradually tapering in R. ornativentris. These elevations were densely crowded, and in some cases several elevations were seen to have fused to form ridges in the R. rugosa pads. Accessory microprocesses completely covered the outermost layer of cells of the elevations. Numerous pile-like microprocesses gradually shortened from the top toward the side of the elevation in R. ornativentris and R. nigromaculata. Those on the top were noticeably longer than those on the side in R. rugosa. The bundles of thick processes radically projected above the top in R. brevipoda porosa. In R. brevipoda porosa nuptial pads were observed under transmission electron microscopy, and the outermost monolayer cells of an elevation were usually keratinized, devoid of organelles and containing closely packed, fine filaments within a dense matrix. The accessory processes also contained dense fibrous matrices. PMID- 8211950 TI - [The scientific nomenclature of domestic animals]. AB - The nomenclature of domestic animals is based on the scientific names of wild ancestors. Bohlken suggested adding the annex "forma domestica" to the binary nomenclature of wild animals in question. However, in such cases where names for domestic animals already exist, the early given names should be used in the annex instead of "domestica". On the other hand, Dennler de la Tour recommended the addition of the term "familiaris" to the scientific names of the wild ancestors. PMID- 8211951 TI - [Salmonella vaccines]. PMID- 8211952 TI - [The clinical case. Hindlimb lameness in a Fleckvieh calf, female, two months old]. PMID- 8211953 TI - [The effectiveness of intravenous administration of large quantities of glucose in the treatment of bovine ketosis]. AB - Glucose in a 40% (w/v) solution (200 g, 400 g or 600 g) was infused intravenously in clinically healthy cattle. On urinalysis, 13%, 19% and 26% respectively of the infused glucose was excreted. In cattle with elevated urinary ketone bodies, only the infusion of 400 or 600 g glucose led to a significant rise in the serum glucose concentration compared to initial values. Only the infusion of 600 g of glucose was followed by a significant decrease in serum beta-hydroxybutyrate 24 hours later compared to initial values. The present results indicate a possibility of improving the results of treatment of ketosis by infusion of high amounts of glucose. PMID- 8211954 TI - [Clinico-chemical blood values in newborn calves. 1. Effects of some internal and external conditions]. AB - In a large dairy cattle herd blood samples taken by venipuncture in newborn calves within 0 to 12 hours after delivery were analysed for hematocrit and fifteen other variables. The time of birth and the time of blood sampling and of first colostrum supply were recorded as well as body weight, sex and breed of the animals. Blood sampling in dairy cows was performed in the course of a herd health programme. The effects of the above-mentioned factors on the blood values of calves were investigated. Comparing the blood values of the pregnant cows with those of their newborn calves led to the result that in calves the measures were higher than (Hkt, Thyroxine), equal to (urea, P, Ca, Zn, Mg, K, Na, TIBC) or below (total protein, albumin, gammaglobulin, cholesterol, coeruloplasmin, Fe, Cu) those of their dams. There was great scattering of the concentrations of Zn, Cu, Mg, Fe, TIBC, total protein, albumin and in hematocrit. Uptake of colostrum caused the concentration of Mg, total protein and gammaglobulin to increase and those of albumin and hematocrit to decrease, leaving the levels of P and blood urea unchanged. PMID- 8211955 TI - [Use of a modified "antigen-capture" enzyme immunoassay for the identification of virus persistence in cattle infected with bovine virus diarrhea (BVD)]. AB - Bovine viral diarrhoea (BVD)/mucosal disease (MD) is an economically important infectious disease of cattle, and persistently infected animals are of central epidemiological significance. The identification of these animals is a prerequisite for further sanitary measures in affected herds. In order to process large numbers of samples an antigen capture enzyme immunoassay (AC-ELISA) for the detection of bovine viral diarrhoea viral antigen in peripheral blood leukocytes of cattle of all ages has been developed. In this communication an improved method for the preparation of samples is described. A total of 563 blood samples was tested using the AC-ELISA and a routine virus isolation procedure on susceptible bovine cells. When compared to virus isolation in cell culture, the sensitivity of the AC-ELISA was 97%. From the samples that were virus negative in cell culture, 99.1% were also negative in the AC-ELISA. There is some evidence that the AC-ELISA discriminated between transiently and persistently infected animals. PMID- 8211956 TI - [First description of a desmoid tumor in a goat and comparative observations to human fibromatosis. Case report]. AB - The macroscopical, histological, and ultrastructural aspects of the abdominal and extra-abdominal desmoid tumour are reported in a 1 1/2-year old goat (breed: Nera Verzasca, Tessin mountain goat). Macroscopically, the disease was characterized by glassy, whitish, very hard, plate-forming masses found in the abdominal wall and in the medial aspect of the upper hind limbs. Histologically, the masses consisted of well differentiated fibroblasts which locally infiltrated the surrounding tissues. No capsule formation was found. On electron microscopy, the cells appeared to be active, young, collagen-producing fibroblasts. The pathogenesis of this disease is unknown. PMID- 8211957 TI - [The effect of food medication alone or in combination with PGF2 alpha on the reproductive performance of swine with SUGD (swine urogenital disease)]. AB - In a large pig production unit 60 postparturient sows were divided at random into 3 groups, each with 20 sows. Group 1 (20 sows) received 30 g Farmavet Trisulfa per os daily from the beginning of the postfarrowing period for 1 week. Group 2 (20 sows) received 30 g Farmavet Trisulfa per os daily from the beginning of the postfarrowing period for 1 week, and in addition were given 3 mg Gabbrostim 24-48 hours after farrowing in a single i.m. application. Group 3 (20 sows) untreated control. The following parameters were evaluated: A: number of weaned piglets per sow, B: weaning to service interval in days, C: return to oestrus in percent. Both groups 1 and 2 showed better results when compared to the control group. Group 2 was superior to group 1. PMID- 8211958 TI - [Reproduction data in breeding mares, diseases and losses among suckling foals and preventive husbandry in German stud farms]. AB - By means of a survey, the reproductive rate of mares and the foal losses in ten Thoroughbred, Saddlebred and Pony studs in Germany, mainly from North-Rhine Westfalia, were collected and evaluated. Data for the survey were recorded for 1985-1990. The study also examined the hygienic management in the surveyed studs, and the morbidity rate of suckling foals was obtained for 1990. In addition to the survey questionnaire each stud was visited once. Two studs of each horse group were visited several times every week from March to August in order to evaluate as exactly as possible the husbandry and morbidity of the suckling foals. The main results were: The abortion rate in Thoroughbred and Saddlebred horses was about 4.5%, of the Ponies 1%. After the 299th day of gestation, fetal mortality ranged from 3.2 to 3.5%. In the more intensively observed studs 33% of Thoroughbred foals, 42% of Saddlebred foals and 11% of Pony foals became ill. Saddlebred foals were more frequently affected by respiratory disease while Thoroughbred and Pony foals were mainly afflicted by diarrhea. The scope of husbandry measures was broader and more intensive in the Thoroughbred and Pony studs compared to the Saddlebred studs. PMID- 8211959 TI - [The biologic interaction of movements in the shoulder joint of cats and dogs]. AB - The shoulder joint is a free joint which enables the free forelimb to describe curves in space, in order to perform movements and for locomotion. The movements can be measured in three planes: flexion-extension, abduction-adduction and rotation. The extent of movement in the cat, the German Shepherd and the Dachshund are described and the efficacy for these species and breeds is discussed. PMID- 8211960 TI - [Perioperative anesthesiological management in multiply-traumatized dog and cat patients]. AB - The consecutive steps in anaesthesia management of polytraumatized dogs and cats are described. First of all care must be taken of the respiration, the cardiovascular circulation and the central nervous system. Analgesia plays an important role even at this stage. After stabilizing vital functions in the phase of primary care, cautious anaesthesia management is required for life-saving surgical procedures in the phase of secondary care. Modified balanced anaesthesia has been well proven in polytraumatized small animal patients. PMID- 8211961 TI - [Blood group typing in the cat]. AB - Blood group serological diagnosis in cats is clinically relevant for the prophylaxis of blood group incompatibility reactions. In permanent blood donors, cats used for breeding and recipients with a history of prior blood transfusions, testing should consist of blood typing and antibody detection. As test sera and test cells are not commercially available and since parallel tests for various antibody qualities are necessary, they are usually performed in specialized laboratories. Incompatibility testing has a practical clinical relevance in finding a serological diagnosis before each blood transfusion and in cases of kitten mortality. In emergency situations, cross matching can be performed on slides as a screening test. Negative slide test results then should be verified using the more sensitive test tube or microtiter plate tests. PMID- 8211962 TI - [Urine characteristics in dogs with diabetes mellitus. Is there a diabetic nephropathy in the dog?]. AB - Dogs with spontaneous Diabetes mellitus were checked at regular intervals for protein excretion in the urine. A large number of dogs developed a proteinuria, very marked in some cases, with excretion of primarily macroproteins. PMID- 8211963 TI - [The intraerythrocytic acid-base status in dogs]. AB - The determination of the intracellular acid-base state is reported in this paper, using erythrocytic haemolysate in dogs as an example. Reference values are given for 217 clinically healthy dogs. The effects of various selected stages of illness and additional stresses on the erythrocytic acid-base equilibrium are reported and compared with acid-base changes in the blood. The metabolic acidosis observed may occur earlier and be stronger in the intracellular space than in the blood. There seems to be a closer correlation between a disturbed intraerythrocytic acid-base equilibrium and the degree of clinical symptoms than between the (commonly investigated) acid-base changes in the blood and the clinical presentations. The investigation of the blood alone does not provide a satisfactory indication of the patient's acid-base state and of the necessity for treatment. PMID- 8211964 TI - [Paralytic myoglobinuria in greyhounds]. AB - In five Greyhounds the provisional diagnosis of paralytic myoglobinuria was confirmed by means of serum enzyme examination and urine analysis. The importance of creatine kinase examination is emphasized. The worsening of the condition was prevented by prompt therapy with massive water and electrolyte infusion of the affected dogs. Recovery was achieved in all cases. PMID- 8211965 TI - [Anesthesia and immobilization in reptiles]. AB - In reptiles anesthesia is recommended not only for painful treatment but also for diagnostic procedures like radiology, sonography, endoscopy and MRI. Special attention should be directed to the anesthetic regimen because of anatomical and physiological differences to mammals. To achieve optimum body temperature (normally 25-30 degrees C) preanesthetic heating is useful. In most cases ketamine hydrochloride is used as an injectable anesthetic. Our own anesthesias (n = 263) are compared to those in the literature. Important disadvantages are species-specific dosages between 15 and 220 mg/kg body weight and poor relaxation. The results of 132 anesthesias performed by the authors using Isoflurane are discussed with reference to the literature. The main advantages were independence of species-specific problems and excellent analgesia and relaxation. Due to total relaxation, manual intermittent positive-pressure ventilation (IPPV) is necessary. PMID- 8211966 TI - Scanning electron microscopic study of the collagen networks of the normal mucosa, hyperplastic polyps, tubular adenoma, and adenocarcinoma of the human large intestine. AB - The three-dimensional structure of the collagen network of normal mucosa, hyperplastic polyps, tubular adenoma, villous adenoma and adenocarcinoma of the human large intestine was examined by scanning electron microscopy after cell maceration with a low temperature NaOH solution. In the normal large intestine, the surface of the sub-basal laminar collagen sheath lining the crypts was generally smooth. In hyperplastic polyps, the crypts extended and the sub-basal collagen network protruded from the surrounding normal tissue. The sub-basal laminar collagen sheath was more densely arranged near the openings of the crypts and on the luminal surface than in deeper regions of the crypts. In tubular adenoma, the tumor glands showed meandering, bending, and divisions. The sub basal laminar collagen sheath was composed of densely packed collagen fibrils. In villous adenoma, the sub-basal laminar collagen sheath formed foliate or linguiform villous cores projecting sharply into the lumen. In adenocarcinoma, the sub-basal laminar collagen sheath exhibited a dense arrangement of fibrils in the central region of the tumor. Toward the marginal region, the collagen sheaths surrounding tumor glands became thinner, and at the edge of the marginal region, basket-like collagen sheaths were observed around individual tumor cells infiltrating the interstitium. Such a tumor lesion was frequently surrounded by a thick collagen fiber zone. PMID- 8211967 TI - Effects of changes in afterload on regional wall motion in acute ischemic canine heart. AB - The aim of the present study was to examine effects of changes in afterload on regional myocardial motion in acute ischemia. Ischemic and non-ischemic segment lengths of the left ventricular free wall were measured by miniature ultrasonic gauges in eleven open chest dogs with the pericardium preserved. In a stable state after left anterior descending coronary artery occlusion, peak left ventricular pressure was varied by the infusion of angiotensin II (n = 8) and sodium nitroprusside (n = 8). To exclude effects of preload on the responses, end diastolic lengths of the non-ischemic region before and during infusion of each drug were matched with vena caval occlusion. When peak left ventricular pressure elevated from 113 +/- 2 (mean +/- S.E.)mmHg to 145 +/- 6, in isovolumetric contraction phase, degree of active shortening in the non-ischemic region and that of paradoxical expansion of the ischemic region did not change. In ejection phase, active shortening of the non-ischemic region decreased from 1.38 +/- 0.11 mm to 1.06 +/- 0.10 but that of the ischemic region remained unchanged. Stroke volume decreased from 14.5 +/- 1.3 ml to 10.8 +/- 1.0. When peak left ventricular pressure decreased from 111 +/- 4 mmHg to 101 +/- 6, in isovolumetric contraction phase, active shortening of the non-ischemic region decreased from 0.90 +/- 0.13 mm to 0.76 +/- 0.15 and paradoxical expansion of the ischemic region reduced from -0.95 +/- 0.11 mm to -0.80 +/- 0.11. In ejection phase, shortening of the non ischemic region increased from 1.05 +/- 0.13 mm to 1.31 +/- 0.15 but that of the ischemic region did not change. Stroke volume increased from 11.5 +/- 1.3 ml to 14.0 +/- 1.4. These results indicate that in acute ischemia, changes in isovolumetric shortening of the non-ischemic region and paradoxical expansion of ischemic region are related with each other in isovolumetric contraction phase when afterload is altered and suggest that stroke volume is affected by the shortening of ejection phase in the non-ischemic region. PMID- 8211968 TI - Chronic treatment with anti-endothelin antibodies fails to modify the development of hypertension in stroke-prone spontaneously hypertensive rats and DOCA-salt hypertensive rats. AB - This study was designed to assess whether blocking endogenous endothelin with anti-endothelin antibodies could alter the development of hypertension in stroke prone spontaneously hypertensive rats (SHR) and DOCA-salt treated rats. Specific anti-endothelin antibodies were produced in rabbits by standard methods. The amount of anti-endothelin antibodies employed in this study blocked the hypertensive effect of endothelin-1, 750 ng/kg, by 55% in conscious rats. Intravenous injection of anti-endothelin antibodies as a bolus twice a week for 3 weeks did not affect the rise in blood pressure of stroke-prone SHR (268 +/- 8 mmHg, n = 8) compared to control stroke-prone SHR (256 +/- 7 mmHg, n = 8) treated with normal rabbit serum. Intravenous administration of anti-endothelin antibodies in a same manner also failed to alter the development of hypertension in DOCA-salt treated rats (160 +/- 6 mmHg in anti-endothelin antibodies-treated group, n = 7 compared to 164 +/- 5 mmHg in normal rabbit serum-treated group, n = 7). The administration of anti-endothelin antibodies did not induce any significant changes in body weight, urine volume and urinary sodium excretion in stroke-prone SHR and DOCA-salt treated rats compared to those treated with normal rabbit serum. These findings suggest that circulating endothelin might not play a major role in the regulation of blood pressure in stroke-prone SHR and DOCA-salt treated rats. PMID- 8211969 TI - New double-barreled, ion-sensitive microelectrodes for measuring intracellular Cl activities in rabbit renal collecting ducts. AB - The use of the conventional ion-sensitive double-barreled microelectrodes has been unsuccessful for studying small epithelial cells such as those of the collecting duct because of the difficulty in obtaining the ideal electrodes for impaling cells. We developed a new type of ion-sensitive, double-barreled microelectrode of a size and tip configuration ideal for use in impaling small cells such as the principal cells (PCs) of the cortical collecting ducts, and remaining therein, for more than 30 min. The electrodes were pulled in two steps. The first includes the reciprocal twisting of two parallel glass capillaries, without pulling, to form a round, nontortuous fused glass capillary in the puller. In the second step, the round, fused straight capillaries are pulled so as to form the tip. This resulting procedure enabled us to impale the PCs without altering their cell membrane potentials. The basolateral membrane voltage (Vb) in PCs of the cortical collecting ducts was -69.1 +/- 1.6 mV (n = 8) and intracellular Cl- activity ([Cl]i) in PCs of the cortical collecting duct was 11.8 +/- 0.9 mmol/liter (n = 5). Changing the concentration of Cl- in the ambient solution showed that the basolateral cell membrane of the PCs was highly permeable to Cl-. This new electrode will help to obtain new information on intracellular ion handling, with the electrodes applied to the collecting duct cells. PMID- 8211970 TI - Fate of orally administered triethylenetetramine dihydrochloride: a therapeutic drug for Wilson's disease. AB - Triethylenetetramine dihydrochloride (TETA) is a therapeutic drug for Wilson's disease. We developed a simple fluorometric method for detection of TETA in biological fluids by using high-performance liquid chromatography (HPLC), and examined TETA concentrations in the serum and urine of two healthy adults who were given TETA orally. No TETA peak was detected in the serum. The amount of TETA in the urine of the two adults was only 1.6 and 1.7% of the dose administered. However, a large unidentified peak appeared in the urine after oral administration. This peak was not observed in a mixture of TETA and control urine or in urine before TETA administration. When the urine after TETA administration was analyzed after hydrolysis with HCl, the unidentified peak disappeared, while the TETA peak increased. These findings indicate that the substance which yielded the unidentified peak is a metabolite of TETA, suggesting that most of the TETA administered is metabolized and then excreted in the urine. PMID- 8211971 TI - Circadian rhythms of blood pressure and heart rate in patients with human T lymphotropic virus type-I-associated myelopathy. AB - Noninvasive ambulatory blood pressure and heart rate monitoring were used to investigate cardiovascular dysfunction in patients with human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy (HAM). The subjects were 23 patients with HAM, and 23 sex- and age-matched normotensive healthy volunteers (controls). Circadian rhythms of blood pressure and heart rate were present in both the HAM patients and controls. Amplitudes and the 24-hr mean systolic and diastolic blood pressures were significantly lower in the patients than in the controls. The 24 hr mean heart rate was significantly higher in the patients, the difference being particularly marked during the night. Differences in the acrophases of the systolic and diastolic blood pressures and heart rate between patients and controls were small but still significant. These results suggest that subclinical cardiovascular autonomic dysfunction is present in HAM patients. PMID- 8211973 TI - The biosynthesis of a cytotoxic protein, alpha-sarcin, in a mold Aspergillus giganteus. I. Synthesis of prepro- and pro-alpha-sarcin in vitro. AB - The biosynthesis of alpha-sarcin, a ribosome inactivating protein (16.9 KDa) was studied in a mold Aspergillus giganteus. The fungus begins to secrete alpha sarcin after reaching a stationary phase around 50 h of culture. The synthesis of alpha-sarcin was shown to be induced at the transcriptional level since the mRNA level of alpha-sarcin, titrated by immuno-precipitation with anti-alpha-sarcin antibodies of translation products in wheat germ cell-free system, was increased synchroniously with the production of the protein. The immuno-precipitates specific for alpha-sarcin contained two species of proteins of 22.5 and 18.5 KDa. The former was localized in the supernatant and the latter was segregated in the microsomes of the wheat germ system. The 22.5 KDa protein was thought to be the primary product of alpha-sarcin, although N-terminal methionine was removed, because it was the only product when the microsomes were solubilized by Triton X 100 prior to translation in the cell-free system. These results indicate that alpha-sarcin is synthesized as 22.5 KDa prepro-alpha-sarcin and is processed cotranslationary into 18.5 KDa pro-alpha-sarcin in endoplasmic reticulum as usual secretary proteins. PMID- 8211972 TI - Treatment of myasthenia gravis: a comparison of the natural course and current therapies. AB - Ninety-five patients with generalized myasthenia gravis were followed for 10 years to evaluate the long term effects of prednisolone, thymectomy, or both, and they were compared with a group only with anticholinesterase treatment. Only 15.0% of the patients with anticholinesterase alone had showed improvement 10 years after the onset, but more than 60% of those treated with prednisolone, thymectomy, or both showed improvement. Especially thymectomy induced complete remissions at 10 years after surgery in more than 20% of the patients. There was no difference between the histology of the thymi and clinical severity, or anti acetylcholine receptor (AChR) antibody titer. In patients who showed improvement classified "good" of higher 10 years after thymectomy with or without prednisolone, anti-AChR antibody titers swiftly decreased to 37.8% of the value before surgery, and remained low thereafter. This result suggests that the marked decrease in anti-AChR antibody titers within 1 month after thymectomy is a favorable prognostic sign in myasthenia gravis patients who have undergone thymectomy. PMID- 8211974 TI - A newborn case of extrarenal malignant rhabdoid tumor. AB - Malignant rhabdoid tumor is initially differentiated from renal tumors and characterized by extremely rapid growth. We report a newborn case of extrarenal malignant rhabdoid tumor and review the literature. PMID- 8211975 TI - A rare case of isolated atrial discordance with primary atrial situs inversus. AB - A newborn with isolated atrial discordance complicated by primary atrial situs inversus and dextrocardia is reported. She received a Mustard's corrective procedure with a good clinical outcome. To our knowledge, this is the third report of a patient with isolated atrial discordance and viscero-atrial discordance or ambiguus. PMID- 8211976 TI - Production of dihydrofolate reductase by an improved continuous flow cell-free translation system using wheat germ extract. AB - We have examined the characteristics of protein synthesis in an improved continuous flow cell-free translation system prepared from wheat germ extract with dihydrofolate reductase mRNA as the translated message. Continuous buffer flow and separation of the product from the reaction mixture were accomplished by the use of a modified Amicon ultrafiltration chamber as the reaction vessel. The system worked for 19 hours and produced 1.52 nmol (27.4 micrograms) of enzymatically active dihydrofolate reductase. PMID- 8211977 TI - Overcoming of vincristine resistance in HL-60 human promyelocytic leukemia cell line by dipyridamole. AB - Dipyridamole enhanced the anti-cancer activity of VCR toward both wild type HL-60 and VCR-resistant subline, HL-60/R, which had a 15 fold greater resistance to VCR as compared with the wild type cell line. The resistance to VCR of HL-60/R cells was associated with a marked decrease in the intracellular VCR accumulation. After incubation with VCR for 24 hrs, 0.61 and 0.24 pmol VCR per one million cells were accumulated in the wild and the resistant cells, respectively. Dipyridamole dose-dependently increased the intracellular VCR accumulation in the wild type cells and also it restored the intracellular VCR accumulation in the VCR-resistant cells. Addition of 10 microM dipyridamole to the culture medium enhanced the intracellular accumulation of VCR during 24 hr incubation by 2.6 fold and 6.0 fold in HL-60 and HL-60/R cells, respectively. The VCR-resistance in HL-60/R cells was able to be overcome by the addition of 2.5 microM dipyridamole to the culture medium. This concentration of dipyridamole could be obtained by the intravenous administration without severe adverse effects. These results indicate that dipyridamole should be effective in the treatment of patients with hematologic malignancy resistant to VCR. PMID- 8211978 TI - Nutritional improvements of soy protein isolate by different levels of methionine supplementation in pregnant rats. AB - The effects of various levels (0, 0.3, 0.4, 0.5, 0.7, 1.0 and 1.5%) of methionine supplementation to a 10% soy protein isolate (SPI) diet were investigated in pregnant and nonpregnant rats in terms of body weight gain, food efficiency, net protein utilization (NPU), growth of the conceptuses and free methionine concentration in the dam's plasma. Supplementation of 0.3 to 0.7% methionine resulted in increases in the weights of the body, fetus and placenta and improvements of food efficiency and NPU in both groups of rats. The extents of increases or improvements of these parameters were more in pregnant rats than in nonpregnant rats, though they were similar in each group independent of the dietary methionine level. No beneficial effects on body weight gain, food efficiency or reproductive performance were observed in rats fed diets with 1.0 or 1.5% methionine. The concentrations of free methionine in the plasma were increased by methionine supplementation to the diet and were consistently higher in nonpregnant rats than in pregnant rats at each level of methionine supplementation. From these results, we proposed that a level of 0.5% methionine (intermediate between 0.3 to 0.7%) is optimal for supplementing 10% SPI diet for rats. The appropriateness of this level is discussed in relation with the methionine equipment of growing rats. PMID- 8211979 TI - Incidence of ultrasonographically-detected thyroid nodules in healthy adults. AB - We studied the incidence of thyroid nodules in healthy adults, who had no history of thyroid disease, in Tokushima, Japan, where goiter is not considered endemic. Examination was performed by palpation and using a 10-MHz real-time sonographic scanner. Palpable thyroid nodules were present in two (0.9%) of 227 men and in four (1.8%) of 224 women. On the other hand, nodules were detected by ultrasonography in 42 men (18.5%) and 47 women (21.0%). There was no significant difference in the incidence detected by ultrasonography between men and women in any of the age groups, except in men above 60 years old. It is concluded that thyroid nodules are not an uncommon disorder even in men. Since, clinically, the incidence of nodularity appears to be higher in women than in men, there may be difference between men and women in the development of nodules until they become clinically detectable. PMID- 8211980 TI - Nephropathy in patients with cyanotic congenital heart disease. AB - Older pediatric patients with cyanotic congenital heart disease (CCHD) often develop nephropathy. Although felt to be secondary to glomerular dysfunction, there have been only a few papers examining renal tubular abnormalities in such patients. We therefore evaluated renal function in 16 patients with CCHD aged 3 to 28 years. The six oldest patients (aged 15 to 28 years), had documented proteinuria and low creatinine clearance levels. The urinary concentration of microalbumin was increased when compared to control values in 7 of the 16 patients; six of the patients had proteinuria while one did not. Urinary levels of N-acetyl-beta-D-glucosaminidase (NAG) were elevated in 14 patients including those without proteinuria. Concentrations of blood urea nitrogen and creatinine as well as serum and urinary concentrations of beta 2-microglobulin levels were elevated in certain patients. The serum concentration of uric acid was notably greater in all CCHD patients relative to controls. Furthermore, serum uric acid concentrations and urinary microalbumin levels correlated with patient age. In conclusion, renal tubular dysfunction as well as glomerular dysfunction occur in patients with CCHD. Urinary NAG may be useful as an early marker for the early detection of tubular dysfunction, while urinary microalbumin levels are useful in assessing glomerular dysfunction in these patients. PMID- 8211981 TI - Predictive electrocardiographic score for evaluating prognosis in patients with Duchenne's muscular dystrophy. AB - Electrocardiographic changes were evaluated in 20 patients with a diagnosis of Duchenne's muscular dystrophy (DMD) for a period of 4 to 9 years preceding their death. Certain common electrocardiographic findings were noted in patients during the terminal stage of their disease, and may have prognostic significance. These included: an R wave in lead V1 of less than 0.6 mV, in lead V5 of less than 1.1 mV, and in lead V6 of less than 1.0 mV; abnormal T waves in leads II, III, a VF, V5 and V6; cardiac conduction disturbances; premature ventricular contractions; and sinus tachycardia. A predictive scoring system was proposed based on these findings. The predictive scores for patients who died primarily from cardiac failure were significantly higher than for patients who died primarily from respiratory failure. This score increased to over 10 points as the patient's clinical condition deteriorated. In conclusion, a predictive score is useful in managing patients with DMD, particularly when evaluating for possible cardiac failure. PMID- 8211982 TI - Application of nuclear magnetic resonance (NMR) spectroscopy to legal medicine- ATP quantitation in tissue with 31P-NMR. AB - NMR spectroscopy can be used to identify and determine various molecular species in organs and tissues, and can provide information on the condition of their presence. We used NMR spectroscopy to examine postmortem changes in rabbits. ATP levels could be determined with ATP beta-position phosphorus atom signals in 31P NMR spectra of tissue samples used as parameters. Changes over time in myocardial and limb muscular ATP levels were examined from just after death due to various causes to 7 hours after death, and the following results were obtained: 1. Myocardial ATP levels were low in groups with pronounced anoxia just before death. 2. Among groups with identical causes of death, decreases in myocardial ATP levels were larger the more pronounced was anoxia. Findings 1 and 2 are applicable to determination of acute cause of death considered otherwise difficult to detect in legal medical practice. 3. The decrease in ATP level just after death was smaller in limb muscles than in myocardium, and changes over time in the decrease in ATP after death could be observed. This finding may be applicable to the estimation of passage of time after death, a problem of great import in legal medicine. PMID- 8211983 TI - Effects of methylmercury on the brain of infant rats reared artificially. AB - Fetal Minamata Disease leads to cerebral palsy, blindness, and deafness accompanying microcephaly. Fetal Minamata Disease has been considered to be exposed to methylmercury during mid and late gestation periods. Brain development in the late gestation in human seems to be equivalent to that in the postnatal stage in rats and mice. Artificial rearing systems for infant rats exclude the maternal and nutrient factors. We administered methylmercury to the infant rats in the artificial rearing system attempting to produce an animal model for Fetal Minamata Disease. Brain weight and brain weight/body weight ratio decreased, and pyknotic degeneration of the nerve cells in the inner granular layer of the cerebellum increased in the groups treated with methylmercury. But, we could not observe drastic degeneration in their brains which mimicked Fetal Minamata Disease in human. PMID- 8211984 TI - The biosynthesis of a cytotoxic protein, alpha-sarcin, in a mold of Aspergillus giganteus. II. Maturation of precursor form of alpha-sarcin in vivo. AB - Since Aspergillus giganteus ribosomes are sensitive to their own product, alpha sarcin, we studied how resistance of protein synthesizing machinery is conferred in the cells. Immunoblotting analysis of a cell-extract prepared from mycelia of alpha-sarcin-producing phase showed two anti-alpha-sarcin reactive proteins which have molecular weights of 18.5 KDa and 16.9 KDa. The former and the latter were identified as the precursor and the mature forms of alpha-sarcin, respectively. Electronmicroscopic observation examining the location in situ by labeling with protein A-gold suggested that alpha-sarcin-related proteins are exclusively localized in large and small vacuoles. The small vacuoles, distributed near cell wall, appear to be involved in maturation and in the secretion of the protein. The present results suggested that alpha-sarcin is synthesized in an inactive precursor form and segregated in the membrane compartment through the synthesis and the maturation of alpha-sarcin in the cells. PMID- 8211985 TI - Study on digestibility and energy availability of pulses (peanuts and kidney beans) in men. AB - Four male Japanese students were fed a semisynthetic diet that included rice and whole eggs as protein sources for seven days (basal diet period), and in the following seven days (test diet periods), peanuts and then, kidney beans replaced part of the sugar in the basal diet. Urine and feces were collected throughout the periods and the contents of nitrogen, fat and energy in these excreta were determined. The results obtained were: 1) Digestibility of protein was 95.1 +/- 7.9% for peanuts and 84.8 +/- 3.7% for kidney beans. 2) Digestibility of fat was 83.5 +/- 8.5% for peanuts and 82.4 +/- 9.1% for kidney beans 3) The ratio of the total available energy to intake energy (Net Energy Availability) was 86.1 +/- 6.3% for peanuts and 84.8 +/- 3.1% for kidney beans. PMID- 8211986 TI - Autopsy analyses of the muscular dystrophies. AB - Life span, causes of death, weight of heart, liver, brain, and main pathological changes of internal organs were analysed on 329 autopsy cases of muscular dystrophies. These included 249 cases of Duchenne muscular dystrophy (DMD), 3 Becker muscular dystrophies (BMD), 14 limb-girdle muscular dystrophies (LGMD), 3 fascioscapulohumeral muscular dystrophies (FSH), 18 Fukuyama type congenital muscular dystrophies (FCMD) and 17 myotonic dystrophies (MyD). In DMD the life span has definitely prolonged in recent years. Pulmonary infection, which was once the major cause of death, has greatly decreased in recent years. Instead, respiratory and cardiac failures caused by dystrophic changes of respiratory and cardiac muscles were more closely related to the causes of death in many recent cases. Myocardial fibrosis was observed in most of the patients with DMD, BMD, LGMD, FCMD and MyD. The distribution of cardiac lesions was similar in BMD, LGMD and FCMD as in DMD. In MyD the disorders involved more frequently conductive muscles resulting in arrhythmias. The dystrophic cardiomyopathy seemed to be a part of the essential changes in all types of muscular dystrophy, although different in intensity and rate of morbidity. Alzheimer's neurofibrillary changes were observed in the brain of some cases of FCMD and MyD, suggesting the possibility of precocious aging of the brain in some patients of the muscular dystrophies. PMID- 8211987 TI - Improving accounts receivable: an introduction to the key functions. PMID- 8211988 TI - Analysis of the collection cycle. PMID- 8211989 TI - Preadmission and preregistration. PMID- 8211990 TI - Admitting and registration. PMID- 8211991 TI - Using automation to control receivables: how computers can improve the revenue cycle. PMID- 8211992 TI - Medical record department's leadership role in receivables management. PMID- 8211993 TI - Strategies to optimize DRG reimbursement. PMID- 8211994 TI - Managing installment payment arrangements. PMID- 8211995 TI - Managing bad debt and charity care accounts. PMID- 8211996 TI - Selecting and monitoring external collection agencies. PMID- 8211997 TI - Performance standards and performance monitoring. PMID- 8211998 TI - Interactions between neuropathy target esterase and its inhibitors and the development of polyneuropathy. AB - This paper combines new and old data in order to offer a modified perspective of the mechanism of organophosphate-induced delayed polyneuropathy. Neuropathy target esterase (NTE) is though to be the molecular target and neuropathy to be initiated with a two-step mechanism: progressive inhibition of NTE and aging of the phosphorylated enzyme. When neuropathic organophosphates modify more than 70% of NTE in this way, neuropathy develops 2 weeks later. Other chemicals producing an inhibited NTE, which is incapable of aging, were thought to be not neuropathic. When given before a challenging dose of a neuropathic organophosphate they protect animals from neuropathy. However, recent evidence indicates that aging may not always be essential in causing neuropathy. In fact, mipafox and methamidophos as well as certain classic protective inhibitors such as carbamate and sulfonyl fluoride form an inhibited NTE which apparently does not age and yet produces neuropathy. We propose that all NTE inhibitors may have the potential to cause neuropathy. In analogy with pharmacological models of drug receptor interactions, NTE inhibitors might have variable intrinsic activities to initiate neuropathy once attached to the protein. Strong neuropathic chemicals require about 70% inhibition of NTE, others 80-90%, and the least potent almost 100%. These differences have been amplified by means of promotion. Different levels of NTE inhibition as caused by different compounds were promoted by the same dose of phenylmethanesulfonyl fluoride to similar degrees of ataxia. Conversely nearly complete NTE inhibitions obtained in chicks with different chemicals were promoted to varying severities of ataxia. Protection from delayed polyneuropathy by the least neuropathic inhibitors can be explained by their weak intrinsic activity: occupying NTE, they prevent the binding of more neuropathic compounds. Methamidophos represents a particular example because it is protective at lower doses and neuropathic at high doses. Moreover, the levels of NTE inhibited by methamidophos which can be promoted to neuropathy are lower than those required for classic protective chemicals and higher than those of classic neuropathic OPs. This suggests that methamidophos has an intermediate position between the most and the least neuropathic NTE inhibitors. PMID- 8211999 TI - Benzene metabolism by reconstituted cytochromes P450 2B1 and 2E1 and its modulation by cytochrome b5, microsomal epoxide hydrolase, and glutathione transferases: evidence for an important role of microsomal epoxide hydrolase in the formation of hydroquinone. AB - Benzene metabolism was investigated using two purified rat hepatic MFO systems containing either cytochrome P450 2B1 or cytochrome P450 2E1. Studies performed over a wide substrate concentration range indicate that cytochrome P450 2B1 represents a relatively low-affinity form of cytochrome P450 with respect to benzene metabolism while cytochrome P450 2E1 is substantially more efficient at low benzene concentrations (apparent Km value 0.17 mM). Cytochrome b5 stimulated benzene metabolism by both cytochromes P450 2B1 and P450 2E1. With cytochrome P450 2E1 the stimulation of benzene metabolism by cytochrome b5 was very pronounced (up to 6-fold) at low concentrations of benzene and was most effective (up to 15-fold) with respect to formation of hydroquinone. The metabolites observed in these studies were phenol and hydroquinone. Cytochrome P450 2E1 metabolized phenol with an affinity and capacity comparable to those of benzene. Hydroquinone was the major product formed at all substrate concentrations, while some catechol was formed at all substrate concentrations, while some catechol was formed at higher concentrations of phenol. Phenol metabolism was also stimulated by cytochrome b5. The metabolism of benzene by cytochrome P450 2E1 in the presence of the major microsomal epoxide hydrolase, mEHb, yielded phenol, hydroquinone, and benzene dihydrodiol. Interestingly, the addition of mEHb did not lead to a decrease of the toxicologically important metabolite hydroquinone as might be expected from sequestration of the intermediate benzene oxide to the vicinal dihydrodiol pathway but rather led to a marked (more than 4-fold) increase in the formation of hydroquinone, suggesting catalysis by mEHb of a predominant attack at the homoallylic position rather than at a carbon atom which forms the epoxide ring of benzene oxide. The addition of glutathione transferases plus glutathione did not yield GSH conjugates during benzene metabolism. However, metabolism of phenol by cytochrome P450 2E1 in the presence of glutathione yielded a nonenzymatically formed glutathione conjugate derived from hydroquinone or from an oxidative product of hydroquinone. PMID- 8212000 TI - Metabolism and bioactivation of 3-methylindole by Clara cells, alveolar macrophages, and subcellular fractions from rabbit lungs. AB - 3-Methylindole (3MI), a fermentation product of tryptophan produced by intestinal and ruminal microflora, has been shown to cause pneumotoxicity in several species subsequent to cytochrome P450-mediated biotransformation. Among several species studied, rabbits are comparatively resistant to 3MI-induced pneumotoxicity, especially when compared to goats or mice. In this study, rabbit pulmonary cells and subcellular fractions were used to examine the metabolism and bioactivation of 3MI. A covalent-binding metabolite was produced in 3MI incubations by both Clara cells and macrophages. The addition of the cytochrome P450 inhibitor, 1 aminobenzotriazole, to these incubations inhibited the production of covalent binding metabolite(s) by 94% in Clara cells and only 24% in macrophages. In incubations of Clara cells or macrophages with 3MI and N-acetylcysteine (NAC), a polar conjugate was detected and tentatively identified as an adduct of 3-hydroxy 3-methylindolenine (3H3MIN). Also identified were 3[(N-glutathione-S-yl)-methyl] indole (3MI-GSH) and 3-methyloxindole (3MOI). In rabbit lung microsomal incubations with 3MI and glutathione (GSH), 3MI-GSH, 3MOI, indole-3-carbinol, and a GSH adduct of 3H3MIN were identified. The addition of cytosol to the microsomal incubations with GSH did not increase the rate of formation of the GSH adducts, indicating that cytosolic GSH-S-transferases are not essential in the formation of these metabolites. GSH significantly decreased the covalent binding of an electrophilic metabolite in microsomal incubations. These data suggest that GSH may be important in the mitigation of 3MI toxicity. Furthermore, the comparison of 3MI bioactivation to electrophilic intermediates in Clara cells and alveolar macrophages suggests that 3MI is metabolized by different oxidative pathways in the two different cell types, although the same metabolites were produced by the two cell types. This study shows that rabbit pulmonary enzymes are capable of bioactivating 3MI to reactive intermediates which become covalently bound to cellular macromolecules. This indicates that the relative resistance of rabbits to 3MI-induced pneumotoxicity is probably not due to differences in metabolic enzymes which convert 3MI to reactive intermediates. PMID- 8212001 TI - Prevention of bromobenzene toxicity by N-acetylmethionine: correlation between toxicity and the impairment in O- and S-methylation of bromothiocatechols. AB - Bromobenzene (800 mg/kg, ip) caused severe liver necrosis with massive hemorrhage in the golden Syrian hamster within the first 24 hr. Kidney injury was also observed. Treatment with N-acetylmethionine (NAM) at an ip dose of 1200 mg/kg at 5 hr after bromobenzene administration significantly protected the liver and kidney against injuries. Plasma glutamate pyruvate transaminase and blood urea nitrogen levels were substantially decreased in the NAM-treated animals. Histological evaluations confirmed these results. When the urinary neutral and phenolic metabolites of bromobenzene from NAM-treated and untreated hamsters were isolated and compared by GC and GC/MS, a striking result was observed in terms of O- and S-methylated thiol-containing metabolite formation. The NAM-treated animals showed approximately a 8- to 14-fold increase in the excretion of the four isomeric O- and S-methylated bromothiocatechols. These thiocatechols, which are now known to be the 3,4-series metabolites of bromobenzene, can undergo methylation at either the thiol or the hydroxyl functional group. The excretion of 3-S- and 4-S-methylated bromodihydrobenzene thiolols was also increased significantly in the NAM-treated hamster, but other neutral and phenolic metabolites were relatively unchanged. These results suggest that bromobenzene toxicity in the Syrian hamster may be associated with impaired methylation capabilities, an impairment that could be due to methionine and glutathione depletion. PMID- 8212002 TI - O- and S-methylated bromothiocatechols. AB - Bromobenzene is metabolized by the Hartley guinea pig to two different bromothiocatechols, 4-bromo-2-hydroxythiophenol and 5-bromo-2-hydroxythiophenol. Both the thiol and phenol functional groups of thiocatechol undergo biological methylation. Methylation at the thiol group leads to the formation of (methylthio)bromophenol (S-methylated bromothiocatechol), while methylation of the phenol group leads to methoxybromothiophenol (O-methylated bromothiocatechol). This resulted in the urinary excretion of four O- and S methylated bromothiocatechols. Bromothiocatechols could be formed by dehydrogenation of their corresponding bromodihydrobenzene thiolols. Both the 3-S and 4-S-bromodihydrobenzene thiolols, as S-methylated products, were found as urinary metabolites of bromobenzene in the Hartley guinea pig. All four O- and S methylated bromothiocatechols and two S-methylated bromodihydrobenzene thiolols were also found as urinary metabolites of bromobenzene in the golden Syrian hamster. PMID- 8212003 TI - 1-Nitronaphthalene toxicity in rat lung and liver: effects of inhibiting and inducing cytochrome P450 activity. AB - In rats, 1-nitronaphthalene (1-NN) causes both pulmonary and hepatic toxicity. Pulmonary toxicity is evident as bronchiolar damage, with necrosis of Clara cells and ciliated cells, whereas hepatic injury involves vacuolation of centrilobular hepatocytes. Pretreatment with O,O,S-trimethylphosphorodithioate [OOS-MeP(S)] or p-xylene gave three- to fourfold protection against 1-NN toxicity. These pretreatments also prevented both the increase in lung weight and the rise in gamma-glutamyltranspeptidase and alkaline phosphatase activity in bronchoalveolar lavage fluid normally associated with 1-NN toxicity. Pretreatment with Aroclor 1254 or beta-naphthoflavone (beta-NF) did not alter the LD50 of 1-NN. Aroclor or beta-NF pretreatment did, however, prevent morphological signs of lung injury and any increase in either lung weight or enzyme activity in bronchoalveolar lavage fluid. Liver damage was not prevented by these treatments; indeed, injury was exacerbated and was transferred from centrilobular to periportal areas. In control rats the covalent binding of [1-14C]NN to liver microsomes was eight times greater than to lung microsomes. Pretreatment with OOS-MeP(S) decreased covalent binding to lung microsomes, without affecting binding to liver microsomes. Conversely, both Aroclor and beta-NF slightly increased covalent binding in lung, but increased liver binding by 250-300%. Phenobarbitone also increased binding to liver microsomes by 250-300%, but failed to increase, or alter, the distribution of liver damage. The reported effects of these pretreatments indicate that the toxicity of 1-NN is probably activated by isoenzyme CYP2B1 in lung, but by isoenzymes CYP1A1 or CYP1A2 in the liver. PMID- 8212004 TI - Role of 2,3,5-trichlorophenyl methyl sulfone, a metabolite of 1,2,4 trichlorobenzene, in the induction of hepatic microsomal drug-metabolizing enzymes by 1,2,4-trichlorobenzene in rats. AB - 2,3,5- and 2,4,5-trichlorophenyl methyl sulfides, 2,3,5- and 2,4,5 trichlorophenyl methyl sulfoxides, and 2,3,5- and 2,4,5-trichlorophenyl methyl sulfones (TCPSO2Mes) were detected in the urine of rats dosed with 1,2,4 trichlorobenzene (TCB). After the administration of 1,2,4-TCB to rats, swift decreases in concentrations of 1,2,4-TCB in blood, liver, kidneys, and adipose tissue were observed. On the other hand, 2,3,5-TCPSO2Me appeared in blood, liver, kidneys, and adipose tissue and remained detectable in the blood and the three tissues until 120 hr. The increases in the activities of aminopyrine N demethylase and aniline hydroxylase and the contents of cytochromes P450 and b5 in hepatic microsomes produced by 1,2,4-TCB occurred after increases in the hepatic concentration of 2,3,5-TCSO2Me. 2,3,5- and 2,4,5-TCPSO2Me increased the above four parameters in rat liver microsomes. The inducing intensity of 2,3,5 TCPSO2Me was much higher than that of 2,4,5-TCPSO2Me. 2,3,5-TCPSO2Me was considered to be a potent inducer and to play a principal role in the induction by 1,2,4-TCB. When 1,2,4-TCB was injected ip into bile duct-cannulated rats, little 2,3,5-TCPSO2Me was detected in blood, liver, kidneys, and adipose tissue. In the antibiotic-pretreated rats dosed with 1,2,4-TCB, 2,3,5-TCPSO2Me concentrations in the blood and the three tissues markedly decreased. These findings suggest that the formation of methylsulfonyl metabolites from 1,2,4-TCB depends largely upon the metabolism of some precursor(s) excreted in the bile by intestinal microflora. The increasing effects of 1,2,4-TCB administration on the activities of aminopyrine- and aniline-metabolizing enzymes and the contents of cytochromes P450 and b5 in hepatic microsomes were not observed in the bile duct cannulated rats. These findings provide evidence that the induction of drug metabolizing enzymes by 1,2,4-TCB is not due to the action of 1,2,4-TCB itself but is due to its methylsulfonyl metabolite, 2,3,5-TCPSO2Me. PMID- 8212005 TI - Autoimmune effects of hexachlorobenzene in the rat. AB - We investigated whether autoimmune disregulation underlies the formerly reported induction of IgM hypergammaglobulinemia and lymphoid organ enlargement by hexachlorobenzene (HCB) in rats. To this end blood, liver, and lymphoid organs were collected from male Wistar rats after feeding a semisynthetic diet containing 0, 500, or 1000 mg HCB/kg for 3 weeks. Sera prepared from the blood were analyzed for total and (auto)antigen-specific antibody levels by ELISA, organs were weighed, and spleens were further investigated morphologically using immunohistochemically stained cryosections. Present experiments confirmed the ability of HCB to increase total IgM, but not IgG, levels and to increase relative spleen, lymph node, and liver weights. HCB treatment elevated IgM, but not IgG, levels against single-stranded DNA, native DNA, rat IgG (representing rheumatoid factor), and bromelain-treated mouse erythrocytes that expose phosphatidylcholine as a major autoantigen. Antibody levels against the foreign antigens sheep erythrocytes, tetanus toxoid, and bovine serum albumin remained unaffected. The IgM autoantibodies proved to be polyreactive. Morphometric analysis of spleen sections showed that HCB caused a proportionally equal expansion of all splenic compartments, but when individual spleen weights were taken into account a significantly larger expansion of the predominantly B cell containing marginal zones could be noted. The latter compartment also contained an increased number of macrophages that can be recognized by the monoclonal antibody ED3. The ability of HCB to elevate serum antibody levels against autoantigens, but not foreign antigens, indicates that HCB probably does not act by polyclonal B cell activation. The IgM isotype, the repertoire, and the polyreactivity of the serum autoantibodies suggest that HCB activates a recently described B cell subset shown to be committed to the production of these autoantibodies and associated with various systemic autoimmune diseases. Since the marginal zone is considered to be the splenic lodging site of this B cell subset and since increases of ED3+ macrophages have been associated with autoimmune diseases in the rat, the observed changes of the marginal zones in HCB treated rats is in line with this notion. PMID- 8212006 TI - Quantitation of an epithelial S-phase response in the rat forestomach and glandular stomach following gavage dosing with ethyl acrylate. AB - Gavage dosing of the irritant, ethyl acrylate (EA), has been found to induce hyperplasia in the rat forestomach, but no signs of toxicity in the glandular stomach or in organs remote from the site of dosing. To quantitatively describe this effect as a background for subsequent modeling studies, pulse measurements of the number of S-phase cells were made following a single gavage dose of EA. The time-course of the S-phase response in the forestomach epithelium following a high dose (200 mg/kg or a 4% solution in corn oil) indicated that the number of S phase nuclei was decreased relative to control animals immediately following gavage dosing with a minimum at 6 hr, but that the number of S-phase nuclei increased significantly above control values by 20 hr and remained significantly elevated until at least 48 hr following the gavage dose. A single-dose dose response study with gavage doses of 0, 2, 10, 20, 50, 100, or 200 mg/kg EA and S phase analysis at 24 hr following gavage dosing indicated that a significant increase in S-phase nuclei was evident at doses of 20 mg/kg or higher. Dosing with EA for 2 weeks at dose levels of 0, 10, 50, or 200 mg/kg caused a prolonged elevation of S-phase nuclei only at the 200 mg/kg dose level during the 24 hr following the last gavage dose. Lower doses did not induce a significant increase in the S-phase nuclei. In contrast to the forestomach, the S-phase response of the glandular stomach was transient following a single 200 mg/kg gavage dose, and only a marginal response was observed following multiple 200 mg/kg doses. No effects were observed at lower doses. Comparison of these results to prior determinations of the effect of EA on the concentration of nonprotein sulfhydryls (primarily glutathione) in the forestomach and glandular stomach indicate a correlation of the stimulation in S-phase activity in the forestomach with the repletion and overshoot of tissue nonprotein sulfhydryl levels. PMID- 8212007 TI - Neonatal exposure to paraquat or MPTP induces permanent changes in striatum dopamine and behavior in adult mice. AB - We have recently reported that environmental toxicants, such as DDT, PCBs, pyrethroids, and nicotine can induce permanent functional and neurochemical changes in adult mice when given to neonatal mice during the peak of rapid brain growth. In the present investigation the neurotoxic effects following neonatal exposure to paraquat (N,N'-dimethyl-4,4'-bipyridylium), a broad-spectrum herbicide with structural similarity to the 1-methyl-4-phenylpyridium ion (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which can induce Parkinson's syndrome, and MPTP were studied. Five groups of mice were given paraquat or MPTP orally: group 1, vehicle; groups 2 and 3, MPTP 0.3 and 20 mg/kg; groups 4 and 5, paraquat 0.07 and 0.36 mg/kg when 10 and 11 days old. Neonatal spontaneous motor activity was tested on Day 18 in mice given paraquat 0.36 mg/kg body wt. Adult spontaneous motor activity testing was performed at ages 60 and 120 days. On Day 125 the mice were decapitated and the contents of dopamine (DA), serotonin (5-HT), and metabolites in striatum were analyzed. The results may be summarized as follows: (1) No signs of acute toxicity or differences in weight gain were observed in any of the groups. Nor was any respiratory distress or motor performance dysfunction evident on Day 18 in mice given paraquat 0.36 mg/kg body wt. (2) The behavioral tests at 60 days of age showed a marked hypoactive condition in the mice given paraquat (at both doses) and MPTP (at both doses). (3) At the age of 120 days the hypoactive behavior persisted and appeared even more pronounced. (4) The high doses of MPTP and paraquat--and to a less extent the low doses--reduced the striatal content of DA and metabolites without affecting 5-HT. The altered behavior, together with the dose-dependent reduction of DA and metabolites in neostriata in this study, further demonstrates the susceptibility to low-dose exposure to environmental pollutants during the neonatal period. PMID- 8212008 TI - The toxic effects of formate in dissociated primary mouse neural cell cultures. AB - Primary dissociated mouse cerebrocortical cell cultures containing both neurons and glial cells were used as an experimental model to study the neurotoxic effects of formate, the putative toxic metabolite of methanol. Neural cells were isolated and prepared from the cerebral cortex of fetal CD-1 mice on Gestational Day 15. Mature 7- to 15-day-old monolayer cultures were exposed to formate (0 to 240 mM) for 8 hr at 37 degrees C over a range of extracellular pH (6.0 to 7.6). Cytotoxicity was evaluated by histopathology, changes in membrane integrity (lactate dehydrogenase release, LDH; [14C]adenine nucleotide leakage), and mitochondrial metabolic activity [reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide, MTT]. Similar quantitative estimates of cell injury were obtained by LDH release or [14C]adenine nucleotide leakage from prelabeled cells. Exposure of neural cells produced time- and concentration-dependent toxic responses. The concentration of formate that resulted in 50% LDH leakage after an 8-hr incubation was estimated to be 45 mM. As determined by light microscopy, formate (20 to 60 mM) was specifically neuronotoxic, primarily affecting large polygonal neurons. Higher concentrations of formate (> or = 120 mM) induced nonspecific cytotoxicity. MTT reduction appeared to be a more sensitive endpoint by showing significant toxic effects at 20 mM (8-hr incubation), while significant leakage of LDH occurred only at formate concentrations > or = 60 mM. Total intracellular ATP concentration was significantly decreased following a 20 or 40 mM formate exposure for 8 hr. These results are consistent with the hypothesis that formate may inhibit mitochondrial function resulting in decreased intracellular ATP and formate-induced neurotoxicity. PMID- 8212009 TI - HgEDTA complex inhibits GTP interactions with the E-site of brain beta-tubulin. AB - We have found that EDTA and EGTA complexes of Hg2+, which conventional wisdom has assumed are biologically inert, are potentially injurious to the neuronal cytoskeleton. Tubulin, a major protein component of the neuronal cytoskeleton, is the target of multiple toxicants, including many heavy metal ions. Among the mercurials, inorganic mercuric ion (Hg2+) is one of the most potent inhibitors of microtubule polymerization both in vivo and in vitro. In contrast to other heavy metals, the capacity of Hg2+ to inhibit microtubule polymerization or disrupt formed microtubules cannot be prevented by the addition of EDTA and EGTA, both of which bind Hg2+ with very high affinity. To the contrary, the addition of these two chelating agents potentiates Hg2+ inhibition of tubulin polymerization. Results herein show that HgEDTA and HgEGTA inhibit tubulin polymerization by disrupting the interaction of GTP with the E-site of brain beta-tubulin, an obligatory step in the polymerization of tubulin. Both HgEDTA and HgEGTA, but not free Hg2+, prevented binding of [32P]8N3GTP, a photoaffinity nucleotide analog of GTP, to the E-site and displaced bound [32P]8N3GTP at low micromolar concentrations. This complete inhibition of photoinsertion into the E-site occurred in a concentration- and time-dependent fashion and was specific for Hg2+ complexes of EDTA and EGTA, among the chelating agents tested. Given the ubiquity of Hg2+ in the environment and the widespread use of EDTA in foodstuffs and medicine, these mercury complexes may pose a potentially serious threat to human health and play a role in diseases of the neuronal cytoskeleton. PMID- 8212010 TI - Pathogenesis of cholesteryl lipidosis of adrenocortical and ovarian interstitial cells in F344 rats caused by tricresyl phosphate and butylated triphenyl phosphate. AB - Triaryl phosphates including tricresyl phosphate (TCP) and butylated triphenyl phosphate (BTP) are organophosphates used in the commercial manufacture of plastics, lubricants, and hydraulic fluids. Rat steroidogenic tissues such as adrenocortical (AC), ovarian interstitial (OI), and Leydig cells use an intracellular pathway to store cholesterol (substrate for biosynthesis of steroid hormones) as cholesteryl ester (CE). This pathway and the pathway for uptake of serum cholesterol are less used in Leydig cells of the adult male rat, resulting in a lower CE pool. BTP and TCP caused cholesteryl lipidosis in steroid hormone synthesizing AC and OI, but not Leydig cells in the adult rat. The objectives of this study were to determine if the administration of triaryl phosphate fluids caused a defect in the cholesterol storage pathway of AC and OI cells and to determine the mechanism of action. Female rats received daily oral doses of 0 or 0.4 g/kg TCP in sesame oil vehicle or 1.7 g/kg neat BTP for 40 days. Adrenal glands from both treatment groups and ovaries from TCP-treated rats were heavier than controls. Microscopic and biochemical studies revealed cholesteryl lipidosis composed of CE in the adrenal glands and ovaries in BTP- and TCP-treated rats with the latter group affected most severely. The activity of neutral CE hydrolase (nCEH), an enzyme that converts CE to cholesterol in the uptake and storage pathways, also was inhibited most in the TCP-treated group (97% inhibition compared to that of control). The activity of acyl coenzyme A:cholesterol acyl transferase, an enzyme that esterifies cholesterol to make CE, was depressed 27% compared to that of control adrenal glands of the TCP group, resulting in elevated intracellular cholesterol levels in AC cells. An inhibition of nCEH in the storage and uptake pathways by triaryl phosphates most likely resulted in the striking accumulation of CE in cytoplasmic lipid droplets of AC and OI cells in F344 rats. PMID- 8212011 TI - Sustained effects of pilocarpine-induced convulsions on brain inositol and inositol monophosphate levels and brain morphology in young and old male rats. AB - Cerebral inositol and inositol monophosphates, products of phosphoinositide (PI) turnover, and neuronal injury were studied in young (10 weeks) and old (24 months) male Wistar rats after pilocarpine-induced convulsions. The goal was to explore the association between short-term cholinergic convulsions, brain PI signaling, and changes in the brain morphology in the young and the old rats. Pilocarpine caused convulsions in young rats at a dose of 300 mg/kg, whereas a dose of 175 mg/kg was required to obtain the same effect in old rats. A dose of 5 mg/kg of diazepam was used to terminate the convulsions 2 hr after their initiation; the rats were then examined on Day 5 postpilocarpine. Inositol and inositol monophosphate levels were similar in both the young and the old control rats. Pilocarpine-induced convulsions decreased cerebral inositol and increased inositol-1-phosphate in both the young and the old rats. Inositol-4-phosphate was stable in the young rats but increased in the frontal cortex and the hippocampus in the old rats. Delayed neuronal death also occurred in the convulsing rats, i.e., a variable proportion of neurons appeared shrunken with eosinophilic cytoplasm and pyknotic nuclei. The hippocampus was the most severely affected brain area. These results show that old rats are more sensitive than young ones to short-term pilocarpine convulsions, associated with sustained PI turnover, and brain injury. Mechanisms in addition to cholinergic ones are likely to be involved in the prolonged cerebral effects of cholinergic convulsions in rats. PMID- 8212012 TI - Correlation of the anticholinesterase activity of a series of organophosphates with their ability to compete with agonist binding to muscarinic receptors. AB - Some compounds that inhibit acetylcholinesterase (AChE) activity compete directly with quinuclidinyl benzilate (QNB) binding, a muscarinic antagonist which binds to all subtypes equally, and with cis-methyldioxolane (CD), an agonist that binds with high affinity to the M2 subtype of muscarinic receptors. The relationship between inhibition of AChE activity and the capability to affect muscarinic receptors directly has not been systematically explored. The interaction of eight organophosphates with muscarinic receptors was compared to their ability to inhibit AChE activity in vitro in tissue homogenates from rat hippocampus and frontal cortex, two cholinergically enriched areas of the brain. Of the compounds tested only echothiophate competed for [3H]QNB binding and only at concentrations greater than 100 microM. The anticholinesterase compounds were also tested for their ability to compete with a muscarinic receptor agonist, [3H]CD, which binds with high affinity (approximate KD = 3.5 nM) to 10 and 3% of the muscarinic receptors in the frontal cortex and hippocampus, respectively. The anticholinesterase compounds inhibited high-affinity [3H]CD binding up to 80% and the effects were similar in both tissues. Echothiophate and DFP were potent inhibitors of [3H]CD binding, as were the active "oxon" forms of parathion, malathion, and disulfoton. The parent "thio" forms of these insecticides, however, were much less effective in competing for [3H]CD binding. A similar pattern of potency was observed for the inhibition of brain AChE activity. A strong correlation was found between the ability of a compound to inhibit AChE activity and the ability to compete with [3H]CD binding. These data suggest that the biological effects of cholinesterase-inhibiting compounds may be due to more than their ability to inhibit AChE. PMID- 8212014 TI - Potential benefits of the recombinant DNA techniques. PMID- 8212013 TI - Direct suppression of superantigen-induced IgM secretion in human lymphocytes by 2,3,7,8-TCDD. AB - The superantigen, toxic shock syndrome toxin (TSST-1), can activate T-cells to proliferate and secrete lymphokines and can act as a nominal antigen to induce proliferation and immunoglobulin secretion in human B-cells. 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxicant that produces potent suppression of murine immunocompetence. The present studies were initiated in order to examine the direct effects of TCDD upon human lymphocytes stimulated with TSST-1. TCDD had no effect upon TSST-1-induced T-cell proliferation and produced only a nonsignificant suppression (15%) of TSST-1-induced B-cell proliferation only at the highest concentration tested (30 nM). In contrast, TSST 1-induced B-cell differentiation, as manifested by IgM secretion, was significantly suppressed by TCDD over the concentration range tested (i.e., 0.3 to 30 nM) in trials using B-cells from four separate donors. However, there was obvious variability in the sensitivity to TCDD in that we detected IC50 values of < 0.3, < 0.3, approximately 5.0, and approximately 25.0 nM in the four trials. These results suggest that human B-cell function, following stimulation by TSST 1, can be modulated by direct exposure to TCDD. PMID- 8212015 TI - 1993 Arnold J. Lehman Award. Thomas W. Clarkson. PMID- 8212016 TI - 1993 Burroughs Wellcome Fund Toxicology Scholar Award. Leona Samson and Debra Laskin. PMID- 8212017 TI - 1993 Education Award. Curtis E. Klaassen. PMID- 8212018 TI - 1993 Frank R. Blood Award. Thomas A. Mably. PMID- 8212019 TI - 1993 Merit Award. John Doull. PMID- 8212020 TI - 1993 Achievement Award. David L. Eaton. PMID- 8212021 TI - 1993 Zeneca Traveling Lectureship Award. Terrence J. Monks. Harihara Mehendale. PMID- 8212022 TI - No effect of dieldrin on progesterone production in gilts. AB - The effect of feeding pigs with dieldrin containing feed on the progesterone profile of the estrous cycle was investigated. Eight gilts comprising three controls and five treatment animals were given feed containing 40 ppm of dieldrin for 60 days. Dieldrin levels in mg/kg fat in tissues analysed were; fat 15.15, muscle 18.68, liver 12.21, corpus luteum 13.68, kidney 14.16, serum 2.84 and brain 1.66. On analysing serum progesterone levels no significant difference (P > 0.10) between the progesterone profile of the control and the treatment animals was observed. PMID- 8212023 TI - Effect of chronic consumption of metabisulphite on the integrity of the rat kidney cellular system. AB - The effect of chronic consumption of metabisulphite, a food preservative, on the integrity of the rat kidney cellular system was investigated. The levels of activities of some 'marker' enzymes were measured both before and after administration of between 1 and 15 doses of the chemical compound. Feeding of metabisulphite (5 mg/kg body wt.) to rats resulted in loss of alkaline phosphatase activities from the kidney beginning after the first dose. This was accompanied by a reduction of lactate dehydrogenase activity which was noticed as a secondary reaction, taking place after five daily doses. This was accompanied by an increase in alkaline phosphatase and a decrease in lactate dehydrogenase activities in the serum. An increased urinary excretion of protein and alkaline phosphatase activity was also obtained. Other enzymes assayed (acid phosphatase and glutamate dehydrogenase activities) were not significantly affected in the tissues and urine. All these results indicated that there is cellular damage to rat kidney as a result of chronic consumption of metabisulphite. They also indicate that the damage was primarily on the plasma membrane. The proximity of the soluble portion of the cytoplasm to the plasma membrane also makes it a secondary site of injury in the kidney cell. PMID- 8212024 TI - Effects of linoleic and oleic acid anilides on prostacyclin synthesis and fibrinolytic profile of human endothelial cells in culture: relevance to the toxic oil syndrome. AB - We evaluated the effects of fatty-acid anilides (FAA) on prostacyclin (PGI2) synthesis and on the fibrinolytic properties of human umbilical vein endothelial cells. Preincubation of endothelial cells with oleic- and linoleic-anilides (OAA and LAA, respectively) resulted in a time- and concentration-dependent inhibition of ionophore A23187- and thrombin-induced PGI2 synthesis. However, no significant effects of FAA on arachidonic acid-induced PGI2 synthesis were found, except with 1000 microM LAA which inhibited cyclooxygenase activity after 24 h. In general terms, OAA showed similar inhibitory effects on PGI2 production as did LAA, but with a shifted time course, since the production of PGI2 at 24 h for OAA was similar to that observed for LAA at 2 h. The release of labeled arachidonic acid from cell membranes was significantly reduced (75-85%), after 24 h, with both FAA. The effect of 100 microM LAA on thrombin-induced PGI2 production was rapid (within 15 min) and irreversible after 60 min. The recovery of PGI2 synthesis after LAA treatment was blocked by cycloheximide, suggesting a decrease of phospholipase(s) activity or cessation of enzyme synthesis. Moreover, this reduced PGI2 synthesis was not associated with [3H]adenine release. Our data indicate that FAA induce a significant impairment of stimulated PGI2 synthesis and arachidonic acid release in endothelial cells, acting primarily as inhibitors of phospholipase(s) rather than of cyclooxygenase. Finally, both LAA and OAA induce an anti-fibrinolytic activity in these cells where major changes are observed in the plasminogen activator inhibitor and the urine-type plasminogen activator. PMID- 8212025 TI - Evaluation of knit glove fabrics as barriers to dermal absorption of organophosphorus insecticides using an in vitro test system. AB - Cotton and synthetic knit glove fabrics in combination with an in vitro skin model were used to examine the capability of fabric to decrease the dermal absorption of the organophosphorus insecticides azinphos-methyl, paraoxon, and malathion. Capability for inhibition of acetylcholinesterase was determined in samples of media taken from under the skin barrier after the skin model, with or without fabric protection, had been exposed to the test compounds for 4 h. Acetylcholinesterase inhibitions caused by the direct addition of organophosphorus insecticide to the media were also included in the comparison. Results indicated that the skin model system alone had some capability to serve as a barrier to the transfer of organophosphates. Fabric covering used on the test model increased the barrier between insecticide application and resultant acetylcholinesterase inhibition. The all-cotton, 7-cut knit was especially effective in preventing the absorption of azinphos-methyl, as this organophosphorus insecticide had no capability to cause acetylcholinesterase inhibition when this fabric was used to protect the skin model. Knit glove materials of 100% cotton were demonstrated to be effective in preventing the absorption of paraoxon and malathion. These studies indicate that an in vitro model system can be used in combination with fabrics to study the relationship between clothing and skin as barriers to the absorption of organophosphorus insecticides. PMID- 8212026 TI - Developmental toxicity of methanol in whole embryo culture: a comparative study with mouse and rat embryos. AB - Methanol (MeOH), a widely used industrial solvent, has been proposed as an alternative motor vehicle fuel. Inhaled MeOH is developmentally toxic in both rats and mice but the mouse is more sensitive than is the rat. The contribution of the embryo to this differential sensitivity was studied in whole embryo culture (WEC) using equivalent stage rat (day 9) and mouse (day 8) embryos (plug day = day 0). Rat embryos were explanted and cultured in 0, 2, 4, 8, 12 or 16 mg MeOH/ml rat serum for 24 h and then transferred to rat serum alone for 24 h. Embryonic development of the 2 and 4 mg MeOH/ml groups was not significantly different from the controls whereas the higher concentrations resulted in a concentration related decrease in somite number, head length and developmental score. The 12 mg/ml dose resulted in some embryolethality as well as dysmorphogenesis, while the highest dose was embryolethal. MeOH was dysmorphogenic in vitro in rat embryos at a MeOH concentration comparable to that reported in maternal serum following teratogenic in vivo exposures. Day 8 mouse embryos were explanted and cultured in 0, 2, 4, 6 or 8 mg MeOH/ml culture medium (75% rat serum, 25% Tyrode's salt solution) for 24 h. Embryonic development in the 2 mg/ml MeOH group was not significantly different from the controls but all higher concentration groups had a significant decrease in developmental score and crown-rump length. The high concentration group also suffered 80% embryolethality. Thus, mouse embryos were affected at MeOH concentrations which were not dysmorphogenic or embryotoxic in the rat, suggesting that the higher sensitivity of the mouse to the developmental toxicity of inhaled methanol is due, at least in part, to greater intrinsic embryonal sensitivity of this species to methanol. PMID- 8212027 TI - Repeated exposure to the polychlorinated biphenyl (Aroclor 1254) elevates the basal serum levels of corticosterone but does not affect the stress-induced rise. AB - Previous studies indicate that repeated exposure of weanling male Fischer 344 rats to Aroclor can cause immune system alterations but the pattern of effects suggested the release of corticosteroids may have played a role. Rats were exposed daily by gastric intubation to the polychlorinated biphenyl (PCB) Aroclor 1254 at 0.1, 1.0, 10, or 25 mg/kg for exposure durations of 5, 10 or 15 weeks. By the 15th week of dosing all groups displayed an elevation in the basal level of serum corticosterone but no change in adrenal weight. Further, rats exposed to Aroclor 1254 for 15 weeks and subjected to stress prior to serum collection displayed elevations in corticosterone levels equivalent to stressed control rats. The failure to observe altered adrenal structure indicative of hyperactivity in the presence of increased serum levels of corticosterone suggest these basal increases may be indirect rather than direct effects of Aroclor 1254. PMID- 8212028 TI - Acetylcholine receptor binding characteristics of snake and cone snail venom postsynaptic neurotoxins: further studies with a non-radioactive assay. AB - The binding of postsynaptic neurotoxins from snake and marine cone snail (Conus sp.) venoms to nicotinic acetylcholine receptor (AchR) was investigated with an ELISA-based, non-radioactive assay. Three snake postsynaptic toxins from the long chain group (Naja naja kaouthia cobratoxin, Naja oxiana neurotoxin I, Bungarus multicinctus alpha-bungarotoxin) and short-chain group (Naja naja atra cobrotoxin, Naja oxiana neurotoxin II, and Laticauda semifasciata erabutoxin b) were studied. Both types of snake postsynaptic toxins showed a dose-response with constant AchR (50 micrograms/ml) and varying toxin concentrations (50-0.035 micrograms/ml). The minimum detection limits of the assay for snake toxins ranged from 310 to 1240 ng/ml (40-160 pmole/ml), depending on the toxin. Unlike any of the short-chain toxins, long-chain toxins consistently bound less receptor and reached maximum absorbance levels with toxin concentrations of 10-50 micrograms/ml. Competition for AchR binding between cone snail postsynaptic neurotoxins (conotoxins GI, MI, SI) and alpha-bungarotoxin or cobrotoxin resulted in a dose-response. The postsynaptic conotoxins were uniformly better competitors for AchR binding with alpha-bungarotoxin than with cobrotoxin. Heat stability studies with neurotoxin I, erabutoxin b, or cobrotoxin revealed a loss in AchR binding activity with increasing temperature. alpha-Bungarotoxin heated at 90 degrees C had increased AchR binding activity by 105%, relative to 25 degrees C samples, but lost the majority of its binding activity after 100 degrees C. The enhanced binding of heated alpha-bungarotoxin to AchR was specific, as evidenced by a competitive dose-response with unheated alpha-bungarotoxin, but heated toxin lacked any biological activity in the mouse lethal assay. When conotoxins GI or MI were heated at 100 degrees C, there was no detectable loss in AchR binding activity, and only a slight decrease in mouse lethality. PMID- 8212029 TI - Toxic effects of human pancreatic and snake and bee venom phospholipases A2 on MCF-7 cells in culture. AB - The toxicity of phospholipase A2 (PLA2) has been suggested to be involved in the pathology of a number of severe diseases including septic shock and acute pancreatitis. However, testing the toxicity of these substances is difficult in vivo. In the present study we compared the toxicity of PLA2s from three snake venoms, bee venom and human pancreas on MCF-7 cells grown in culture. Tetrazolium microculture assays were developed to test the cytostatic and cytotoxic effects of PLA2 on MCF-7 cells. These tests are based on the ability of viable cells to reduce a tetrazolium-based compound MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] to a blue formazan product. Leakage of lactate dehydrogenase (LD) from the cells into the culture medium was also measured. There were marked differences in the toxicity of the PLA2s tested. Cobra (Naja mosambique mosambique) venom PLA2 was toxic to the cells at a concentration of 4.5 U/ml. Light microscopic changes were seen in the injured cells after 3 hr treatment. Sixty-seven per cent of cells were dead after 24 hr treatment. Treatment for 4 hr caused irreversible changes in the cells. Leakage of LD was noted from 4 hr onwards. Other snake (Crotalus adamanteus and Laticauda semifasciata) venom PLA2s, even after continuous exposure to 4.5 U/ml caused only slight decreases in values obtained in the MTT test. No morphologic changes suggesting a cytotoxic effect were seen. PLA2 from bee (Apis mellifera) venom had no toxic effect, either. Continuous exposure of cells to human pancreatic PLA2 caused a 15% decrease in the MTT-test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212030 TI - Dithiothreitol generates an activated 250,000 mol. wt form of Clostridium difficile toxin B. AB - The potent cytotoxin of Clostridium difficile, toxin B, is internalized by endocytosis and activated intracellularly by an unidentified mechanism. Here it is shown that dithiothreitol treatment of toxin B resulted in (1) a mol. wt of 250,000 which is the smallest species of this toxin shown to be cytotoxic; (2) an increased endpoint titre; and (3) translocation of plasma membrane-bound toxin across the membrane at pH 4.5. Treatment with dithiothreitol can thus mimic intracellular activation of the toxin. Radiolabelling of highly purified toxin with retained activity, as well as the 32 N-terminal amino acids and the amino acid composition, is also presented. PMID- 8212031 TI - An investigation into the antigenic cross-reactivity of Ophiophagus hannah (king cobra) venom neurotoxin, phospholipase A2, hemorrhagin and L-amino acid oxidase using enzyme-linked immunosorbent assay. AB - The antigenic cross-reactivity of four Ophiophagus hannah (king cobra) venom components, the neurotoxin (OH-NTX), phospholipase A2 (OH-PLA2), hemorrhagin (OH HMG) and L-amino acid oxidase (OH-LAAO) were examined by indirect and double sandwich ELISAs. The indirect ELISAs for OH-NTX, OH-PLA2 and OH-HMG were very specific when assayed against the various heterologous snake venoms and O. hannah venom components, at 25 ng/ml antigen level. At higher antigen concentrations (100-400 ng/ml), there were moderate to strong indirect ELISA cross-reactions between anti-O. hannah neurotoxin and venoms from various species of cobra as well as two short neurotoxins. However, anti-O. hannah hemorrhagin did not cross react with any of the venoms tested, even at these high antigen concentrations, indicating that O. hannah hemorrhagin is antigenically very different from other venom hemorrhagins. Examination of the indirect ELISA cross-reactions between anti-O. hannah PLA2 and several elapid PLA2 enzymes suggests that the elapid PLA2 antigenic class has more than two subgroups. The antibodies to O. hannah L-amino acid oxidase, however, yielded indirect ELISA cross-reactions with many venoms as well as with OH-NTX, OH-PLA2 and OH-HMG, indicating that OH-LAAO shares common epitopes even with unrelated proteins. The double sandwich ELISAs for the four anti-O. hannah venom components, on the other hand, generally exhibited a higher degree of selectivity than the indirect ELISA procedure. PMID- 8212032 TI - Delivery of Duvernoy's secretion into prey by the brown tree snake, Boiga irregularis (Serpentes:Colubridae). AB - Many colubrid snakes, like the more venomous elapid and viperid snakes, can produce and inject an oral secretion that is toxic and may present a human health risk. However, colubrid oral toxins are produced in a Duvernoy's gland and delivered not through a hollow fang, but instead by long, often grooved teeth under low pressure. The possible role of Duvernoy's secretion in functions other than rapid killing of prey make it important to know how and where this secretion is delivered during a feeding strike. We used ELISA analysis to determine the quantity and proportional distribution of Duvernoy's secretion delivered into the integument compared to the viscera during a feeding strike by the colubrid snake Boiga irregularis. We determined that only about 54% (1-5 mg) of the secretion actually reached the viscera and that the rest remained in the integument. The amount reaching the viscera is about three to eight times the i.p. LD50 for mice, but these snakes depend more on constriction than toxins to kill their prey. Consequently, delivery of Duvernoy's secretion by B. irregularis is hypothesized to be part of a digestive function and its toxic properties a byproduct of this role. PMID- 8212033 TI - Inhibition of metalloproteinases in Bothrops asper venom by endogenous peptides. AB - Bothrops asper venom contains a variety of degradative enzymes, including metal ion dependent proteinases as well as low molecular weight peptides. Two of these peptides, pyroglutamate-glutamine-tryptophan (pEQW) and pyroglutamate-asparagine tryptophan are present in crude venom at concentrations of about 4.5 and 1 mM, respectively. Proteinase fractions from B. asper are inhibited from digesting oxidized insulin B-chain in vitro by both of these tripeptides with an IC50 for pEQW of approximately 0.3 mM. Digestion of purified myotoxin MIII from B. asper venom is also inhibited in vitro by pEQW, suggesting that similar inhibition of proteinase activities probably occurs in the venom gland. Inhibitory peptides present in venom allow snakes to be protected from their own toxic proteinases and inhibit hydrolysis of venom proteins during storage in the venom gland. Upon dilution, such as when venom is injected into prey, peptide inhibitors dissociate from the proteinase and allow their activation. A simple procedure for isolation of these inhibitory peptides is described. PMID- 8212034 TI - Localization of toxins in the poisonous mosaic crab, Lophozozymus pictor (Fabricius, 1798) (Brachyura, Xanthidae). AB - A hot aqueous extraction method was used to extract toxins from different parts of the poisonous coral reef crab, Lophozozymus pictor. Contrary to an earlier report that crab toxins do not show localization, the toxicity of L. pictor was found to be consistently high in the gut and hepatopancreas, whereas the muscle was less toxic and the carapace was mildly or non-toxic. Crabs kept in captivity for 10 days showed reduction in toxicity in all parts studied with almost complete loss of toxicity after 24 days. PMID- 8212035 TI - [3H]-saxitoxinol metabolism and elimination in the rat. AB - Tritiated saxitoxinol was used to obtain preliminary information on saxitoxin metabolism in the rat. Sublethal doses of tritiated saxitoxinol (18.9-microCi/kg; 3.8 micrograms/kg) were injected i.v. into each of six rats. Urine and fecal samples were collected up to 144 hr post-injection. Within 4 hr, 60% of injected radioactivity was excreted in urine. No radioactivity was found in feces. High performance liquid chromatography analyses of urine showed that saxitoxinol was not metabolized by the rats. PMID- 8212036 TI - Neutralization of tiger snake (Notechis scutatus) venom by serum from other Australian elapids. AB - Sera from four Australian elapids and one boidid (python) were tested for their ability to protect neonatal mice against the toxic action of tiger snake (Notechis scutatus) venom. Of the five serum samples tested, only serum from Pseudechis australis and Pseudechis porphyriacus were capable of neutralizing the tiger snake venom. In addition, neutralization was shown to be highly variable within serum taken from individual snakes of the same species (P. porphyriacus). Previously, only viperid and colubrid snakes have been shown to possess neutralizing factors against snake venoms. PMID- 8212037 TI - Comparison of in vitro and in vivo biological activity of mycotoxins. AB - In vitro assays developed to screen the cytotoxic activity of chemicals in murine (NIH/3T3) and bovine (BE 12-6) embryonic cells were used to determine the concentrations (microgram/ml) of mycotoxins which caused 50% lethality (LC50). Embryonic cells were seeded in 96 well plates, cultured for 72 hr with dilutions of each individual and combinations of mycotoxins, and stained and counted. Verrucarin A and roridin A had the strongest cytotoxic activity, and ergotamine tartrate was least toxic. Furthermore, results correlated with published values of in vivo activity, indicating this assay can be used for acute toxicity screening of compounds. PMID- 8212039 TI - Bibliography of toxinology. PMID- 8212038 TI - Identification of bis(agmatine)oxalamide in venom from the primitive hunting spider, Plectreurys tristis (Simon). AB - N, N'-bis(4-guanidinobutyl)oxalamide, a novel bis(agmatine)oxalamide, is identified as a major component (8 micrograms/microliters) and the predominant acylpolyamine in venom from the primitive hunting spider, Plectreurys tristis. The function of this compound is unknown since it does not confer insecticidal or fungicidal activity in the systems examined. PMID- 8212040 TI - Low molecular weight factor X activator from Cerastes vipera (Sahara sand viper) venom. AB - Fraction G from Cerastes vipera venom previously purified on Sephadex G100 was refractionated on DEAE-Sephadex A50 column. A factor X activator was obtained. It had a mol. wt of 12,500 and an isoelectric point of 4.4. It shortened the plasma recalcification time of normal plasma, and plasmas deficient in factors V, VII, VIII, IX, XI and XIII, while it had no effect on plasma deficient in factor X or factor II. It had a serine protease activity and a minimal plasmin activity. PMSF, leupeptin and iodoacetamide exerted a pronounced inhibitory effect on its serine protease activity. Polyantivenin could neutralize the coagulant activity of the activator. PMID- 8212041 TI - Purification of protein toxins from Leiurus quinquestriatus hebraeus that modify Na channels. AB - Two protein toxins (Lqh1 and Lqh2) were purified from crude venom obtained from Middle Eastern scorpions, Leiurus quinquestriatus hebraeus, by using cationic exchange chromatography. Lqh1 and Lqh2 were compared to toxin V (Lqq5) obtained from the venom of the North African scorpion Leiurus quinquestriatus quinquestriatus. Lqh1 and Lqh2 were purified to homogeneity; they had mol. wts of 6390 and 5870, respectively; thus both toxins differ in size from Lqq5 (7462). Electrophysiological experiments also suggested that all three toxins are different. In a dose-dependent manner, Lqh1, Lqh2 and Lqq5 lengthened and attenuated propagated compound action potentials (AP) recorded from frog sciatic nerves using the single sucrose-gap technique. Toxins Lqh1 and Lqh2 were found to be more effective than Lqq5 in both lengthening and blocking APs. Voltage-clamp experiments using the vaseline-gap technique on frog skeletal muscle fibres showed that Lqh1 and Lqh2 attenuated the Na current amplitude and slowed inactivation, while Lqq5 primarily lengthened the Na current duration. Increases in the holding potential increase the current attenuation caused by all three toxins. Evidence from sucrose-gap and voltage-clamp experiments suggests that all three toxins bind to Na channels and block them, besides their well-known ability to slow inactivation kinetics. The increased effectiveness of Lqh1 appears to be produced by a slowed rate of exit of the toxin from its binding site. PMID- 8212042 TI - Ciguatera and mannitol: in vivo and in vitro assessment in mice. AB - Mannitol (1 g/kg i.v.) is currently the treatment of choice for acute ciguatera, but confirmation of this treatment's apparent efficacy awaits further experimental or controlled clinical evidence. In mice, mannitol (1 g/kg i.v.) administered before or after i.p. ciguatoxin did not influence the signs of intoxication or the time to death. The effects of oral ciguatoxin differed from those following i.p. ciguatoxin, but again i.v. mannitol provided no detectable benefit. Development of hypothermia was rapid in mice receiving i.p. or oral ciguatoxin and was unaffected by i.v. mannitol. A sublethal i.p. dose of ciguatoxin initially retarded (day 0-4) but then accelerated (day 4-12) the growth of mice. Mannitol (i.v.) had no influence on these effects of ciguatoxin on the growth of mice. Ciguatoxin inhibited responses of isolated diaphragms to nerve stimulation (ED50 = 9 x 10(-11) M), while directly stimulated diaphragms were inhibited by five-fold higher concentrations. Mannitol (50 mM) added to the organ bath did not influence the ciguatoxin-induced inhibition of diaphragm responses to nerve stimulation in vitro. Responses of isolated diaphragm to nerve stimulation were normal in preparations removed from ciguatoxin-treated mice displaying pronounced dyspnoea (gasping). However, responses to nerve stimulation were reduced in preparations removed from mice immediately following death from ciguatoxin. Mannitol (i.v.) partially protected the phrenic nerve-diaphragm from this effect of ciguatoxin in vivo. We conclude that the lethal effects of ciguatoxin in mice probably stem from a central action, and suggest that species differences may account for the absence of any marked beneficial effect of i.v. mannitol in the mouse model for ciguatera in humans. PMID- 8212043 TI - Comparison of the immunogenicity and antigenic composition of ten Central American snake venoms. AB - The immunological reactivity of five crotaline antivenoms for the venoms of ten Costa Rican snakes was determined. Venoms from Bothrops asper, B. godmani, B. lateralis, B. nasutus, B. ophryomegas, B. schlegelii, B. nummifer, B. picadoi, Crotalus durissus durissus and Lachesis muta stenophrys were separated by SDS PAGE, transferred to cellulose nitrate membrane and reacted against five different antivenoms. Antisera used in the immunoblotting were prepared in rabbits to the crotaline venoms from Crotalus viridis viridis (prairie rattlesnake), Crotalus durissus terrificus (South American rattlesnake), Crotalus atrox (western diamondback rattlesnake), and Bothrops atrox (fer de lance). SDS PAGE analysis of the ten venoms indicated that all venoms had components in the high-medium mol. wt (> 15,000) and low mol. wt (< 15,000) range, but they all had at least twice as many components in the high-medium mol. wt range. The venoms of B. nummifer and B. nasutus have the greatest number of bands (24) whereas B. asper has the lowest (17). There appeared to be no difference in immunogenicity between high-medium mol. wt components and low mol. wt components; however, with the venoms of B. nasutus, B. ophryomegas, and B. schlegelii, there were few reactions between antivenoms and low mol. wt components. Half of the ten venoms tested had the highest reactivity with antivenom against B. atrox venom. Two venoms reacted most with antivenom against C. adamanteus venom; one with antivenom to C. atrox venom; one with antivenom to C. v. viridis venom and one with antivenom to C. d. terrificus venom.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212045 TI - Bibliography of toxinology. PMID- 8212044 TI - Crystallization and preliminary diffraction data of two myotoxins isolated from the venoms of Bothrops asper (Terciopelo) and Bothrops nummifer (jumping viper). AB - Two myotoxins isolated from B. asper (myotoxin II) and B. nummifer (myotoxin I) snake venoms have been crystallized and their diffraction properties are described. These myotoxins are phospholipase A2 variants which lack enzymatic activity; B. asper myotoxin II is a lysine-49 phospholipase. Crystals were obtained at room temperature by standard hanging-drop vapour diffusion methods. Crystals diffracted to a resolution of 2.8 and 2.3 A, respectively. PMID- 8212046 TI - Peptide T, a novel bradykinin potentiator isolated from Tityus serrulatus scorpion venom. AB - A bradykinin-potentiating peptide was isolated and characterized from venom of the scorpion Tityus serrulatus by chromatographic techniques followed by biological assays. The complete amino acid sequence (13 residues) of peptide is presented. The peptide potentiated the contractile activity of bradykinin on the isolated guinea-pig ileum, and inhibited the hydrolysis of bradykinin by angiotensin-converting enzyme from B. jararaca plasma and the conversion of angiotensin I to angiotensin II by kininase II from guinea-pig ileum tissue. The peptide also increased the depressor effect of bradykinin on arterial blood pressure in the anaesthetized rat. PMID- 8212048 TI - Purification, sequencing and characterization of single amino acid-substituted phospholipase A2 isozymes from Trimeresurus gramineus (green habu snake) venom. AB - Two phospholipases A2 named PLA2-III and IV were newly isolated from Trimeresurus gramineus (green habu snake) venom in addition to PLA2-I and II reported previously [ODA et al. (1991) Toxicon 29, 157; Fukagawa et al. (1992) Toxicon 30, 133]. Their isoelectric points were determined to be about 4.5. PLA2-III and IV exhibited almost unchanged lipolytic activity toward egg-yolk when compared with PLA2-I. The amino acid sequences were determined by sequencing the native proteins and the peptides produced by enzymatic (Achromobacter protease I and clostripain) and chemical (hydroxylamine) cleavages of the S carboxamidomethylated derivative of the proteins. Both proteins consisted of 122 amino acid residues. When compared with PLA2-I, PLA2-III showed only a single amino acid substitution at the N-terminal position; namely from His to Asn. PLA2 IV also showed a single substitution from Ala to Asp at position 72. It was inferred that these amino acid substitutions between PLA2-I and PLA2-III or IV are due to the single base substitution at the corresponding codons of genes, which might be preserved independently. The unique presence of Phe at position 28, where Tyr is commonly located and assumed to be a part of the Ca(2+)-binding loop, was conserved in both PLA2-III and IV as in PLA2-I. There was no significant difference in the dissociation constants (4.3-5.2 x 10(-4) M) for Ca2+ between these PLA2S and Tyr-28-containing PLA2S. These results suggested that the p-hydroxy group of Try-28 does not play a crucial role in binding of PLA2S to Ca2+. PMID- 8212047 TI - Oedema formation and degranulation of mast cells by phospholipase A2 purified from porcine pancreas and snake venoms. AB - Phospholipase A2 is ubiquitous in nature, with the highest concentrations occurring in pancreatic juice and in the venom of snakes. Local oedema formation is a common feature of the effects caused by snakebite, and indicates an increase in vascular permeability that could be produced by lipid mediators such as lysophospholipids, eicosanoids or PAF release by the enzymatic activity of PLA2. Desalted porcine pancreatic PLA2 exhibited strong oedema-inducing activity in a similar form to PLA2 venom from Naja naja or Crotalus durissus terrificus. Furthermore, all three PLA2S caused the release of histamine from rat peritoneal mast cells. However, non-desalted pancreatic PLA2 that was presented as an ammonium sulphate suspension (3.2 M) had no proinflammatory activity and clearly did not release histamine in vitro. When the enzymatic activity of PLA2 on mast cell membranes prelabelled with [3H] arachidonic acid was determined, a relationship between the enzymatic activity and mast cell degranulation and the minimum oedema dose was observed. However, non-desalted porcine pancreatic PLA2 had the same enzymatic activity as the desalted enzyme but had little proinflammatory activity. This may be due to decreased histamine secretion caused by the presence of ammonium sulphate. Our study supports the idea that the proinflammatory activity of extracellular phospholipases could depend on their ability to cause mast cell degranulation. Moreover, the biological effects of PLA2 are correlated with the specific activities of the enzymes. PMID- 8212049 TI - Properties and amino acid sequence of huwentoxin-I, a neurotoxin purified from the venom of the Chinese bird spider Selenocosmia huwena. AB - By means of reverse phase and ion-exchange high performance liquid chromatography, a neurotoxic peptide named huwentoxin-I was purified from the venom of the Chinese bird spider Selenocosmia huwena. The intraperitoneal and intracisternal LD50 in mice of the toxin were 0.70 mg/kg and 9.40 micrograms/kg, respectively. This toxin at the concentration of 1 x 10(-5) g/ml can irreversibly block the neuromuscular transmission of the isolated mouse phrenic nerve diaphragm preparation in 13.4 +/- 1.3 min (mean +/- S.D., n = 5). The isoelectric point is 8.95 determined by isoelectric focusing electrophoresis. It consists of 33 amino acids including 6 Cys and 6 Lys determined by amino acid analysis. The complete amino sequence of huwentoxin-I was determined. The N-terminal and C terminal residues were Ala and Leu, respectively. The primary structure showed partial homology with that of mu-agatoxins from the funnel-web spider Agelenopsis aperta. PMID- 8212050 TI - The structure of the venom gland of stonefish Synanceja horrida. AB - The structure of the venom gland of stonefish Synanceja horrida was studied using light microscopy, and transmission and scanning electron microscopy. The glands were covered with a fibrous capsule which divided the glandular tissue into many septa which carried numerous nerves and blood vessels. Transmission electron microscopy showed Type I cells with electron-dense material and tubular cisterns, Type II cells with dilated cisterns, sarcoplasmic reticulum and dense secretory granules. The secretory granules were globular and seen in monomer or polymer form. The secretory cells appear to be unique in comparison with the venom gland cells of snakes, scorpions or spiders. PMID- 8212051 TI - Partial purification of two proteins which sensitize ribosomes to gelonin: sensitization is not linked to phosphorylation of ribosomal proteins. AB - Inactivation of ribosomes by gelonin, from Gelonium multiflorum, requires ATP and extraribosomal protein(s) present in the rabbit reticulocyte lysate [SPERTI, S. et al. (1991) Biochem. J. 277, 281-284]. On the anion exchanger Mono Q the activity responsible for the sensitization of ribosomes to gelonin resolves in two peaks which both display a kinase activity on ribosomal proteins. However, staurosporin, an inhibitor of several protein kinases, strongly inhibits phosphorylation of ribosomal proteins without affecting the gelonin-promoting activity of Mono Q peaks. All the evidence collected contradicts a direct link between sensitization to gelonin and phosphorylation of ribosomes. PMID- 8212052 TI - Isolation and characterization of a hemorrhagin from the venom of Calloselasma rhodostoma (Malayan pit viper). AB - The major hemorrhagin (termed rhodostoxin) of the venom of Calloselasma rhodostoma (Malayan pit viper) was purified to electrophoretic homogeneity by Sephadex G-200 gel filtration followed by high performance ion exchange chromatography. The purified hemorrhagin also yielded a single peak in reversed phase HPLC. It had an isoelectric point of 5.3 and a mol. wt of 34,000. Rhodostoxin exhibited potent proteolytic, hemorrhagic and edema-inducing activities but was not lethal to mice at a dose of 6 microgram/g (i.v.). Treatment of rhodostoxin with EDTA eliminated both the proteolytic and hemorrhagic activities completely. The N-terminal sequence of rhodostoxin was determined to be NHEIKRHVDIVVVXDSRFCTK. PMID- 8212053 TI - Dose-response relationship between total cadmium intake and beta 2 microglobulinuria using logistic regression analysis. AB - The dose-response relationship between total cadmium intake and beta 2 microglobulinuria was investigated using logistic regression analysis in order to consider the effect of age on this association. The target population consisted of 1850 inhabitants of the cadmium-polluted Kakehashi River basin in Ishikawa prefecture, Japan. They were divided into 58 subgroups (27 in the men and 31 in the women) by four factors of sex, age, rice cadmium concentration and length of residence in cadmium-polluted areas. Logistic regression analysis was performed for this dose-response relationship, and both age and total cadmium intake were significantly associated with beta 2-microglobulinuria. It was confirmed that total cadmium intake had a significant association with beta 2-microglobulinuria, independent of the aging effect. PMID- 8212054 TI - In vitro inactivation of glucose-6-phosphate dehydrogenase from human red blood cells by acrolein: a possible biomarker of exposure. AB - We have investigated the possibility of utilizing glucose-6-phosphate dehydrogenase (G6PD) as a macromolecular (biological) marker of acrolein exposure. The result showed a dose-dependent inactivation of the erythrocyte G6PD in situ or as a purified enzyme from human erythrocytes or yeast. Amino acid analysis on the chemically modified yeast G6PD showed a formation of a lysine adduct which is probably linked to the inactivation. PMID- 8212055 TI - The mitogenic potential of trichloroethylene in B6C3F1 mice. AB - Male and female B6C3F1 mice were given TCE by gavage for 10 days. No histopathologic changes in the livers from control male and female mice were found. Moderate changes around central veins were noted in male or female mice that received 1000 mg/kg/body weight TCE. Histopathological changes included an increase in cytoplasmic eosinophilic staining and apoptosis around the central veins. Mitosis and DNA synthesis were examined using incorporation of [3H]thymidine into liver cells. Incorporation of [3H]thymidine was significantly increased in the DNA of animals receiving TCE. Total liver DNA extracted from TCA treated mice was not significantly different than those of control groups. Autoradiographic examination of liver sections showed that the incorporation of label in control animals was primarily in perisinusoidal cells. The majority of radiolabel incorporation in TCE-treated mice was found in intermediate zone cells that appeared to be mature hepatocytes. No outstanding differences in the distribution of radiolabel in the liver from male or female mice were noted. When incorporation of [3H]thymidine was quantified by enumeration of labeled hepatocytes following autoradiography, incorporation of the radiolabel into hepatocytes increased proportionally to the applied dose of TCE, but did not increase in peri-sinusoidal cells. Increased mitotic figures in intermediate zone cells resembling mature hepatocytes were found in all mice treated with TCE. These results suggest that liver cell DNA synthesis and mitosis are stimulated by TCE and that these effects may be in part responsible for transformation of liver cells in these mice. PMID- 8212056 TI - Electrocardiographic responses to carbon monoxide and cyanide in the conscious rat. AB - Carbon monoxide (CO) and cyanide (CN), commonly found in exhaust fumes and smoke, act as hypoxic agents in eliciting morbid and lethal effects. This study explored the effects of these two toxicants on the ECG in a controlled and well characterized animal model. Levine-prepared awake female rats were treated with 1500 and 2400 ppm CO for 90 min, CN at 4 mg/kg, or 1500 ppm CO plus 4 mg/kg CN. As in past studies, CO initially induced hyperglycemia and many-fold increases in blood lactate concentration, and rebound increases in blood glucose during recovery. CN produced hyperglycemia, however, there was no glucose rebound, nor was there a significant increase in lactate. CN plus 1500 ppm CO produced glucose changes similar to that of CO alone. CO exposure also induced hypothermia and hypotension, while CN produced little change in these parameters. CO increased heart rate, while CN tended to decrease heart rate. PR interval was increased significantly 4.5-17.0 ms by exposure to CO, with or without combination with CN, while CN alone produced minimal change in the PR interval. QT interval was increased up to 20 ms by exposure to CO, with or without combination with CN. CN alone produced no change in the QT interval. T wave duration was increased up to 22.5 ms by exposure to 1500 ppm CO, with or without combination with CN. CN alone produced minimal changes in T wave duration. There were no changes in duration of the (Q)RS complex or of the R wave. QT interval lengthening was positively correlated with the decrease in systolic blood pressure (0-30 min, r = 0.657, P < 0.05; 0-60 min, r = 0.704, P < 0.05). Hypothermia was correlated with increase in lactate concentration (r = 0.73, P < 0.05) and with decrease in blood pressure (r = 0.69, P < 0.05). No correlation between body temperature and QT interval was observed. The results indicate that CO at the concentrations used in the Levine prepared rat has major effects on the ECG in slowing AV conduction and ventricular repolarization. In contrast, CN at 4 mg/dl has little or no effect on either conduction or repolarization in this animal model. These findings are discussed in light of past animal and human studies. PMID- 8212057 TI - Behavioural effects of piperonyl butoxide in male mice. AB - Piperonyl butoxide was administered to male mice from 5 to 12 weeks of age in the diet at levels of 0 (control), 0.15, 0.30, and 0.60%, and some behavioural parameters were measured. The animals performed three trials in multiple water T maze at 10 weeks of age, and the number of errors was significantly decreased in treatment groups on the 3rd trial, while there was no biologically significant effect of piperonyl butoxide on maze learning. The motor activity of the exploratory behaviour was measured by ANIMATE AT-420 at 8 and 11 weeks of age. At 8 weeks of age, some parameters were increased in the 0.30% group, while there was no consistent compound- or dose-related effect. At 11 weeks of age, some parameters were different in treatment groups, and there were biologically consistent significant effects; i.e., number of movements, movement time, total distance, average speed, and number of turnings increased. From these results, piperonyl butoxide showed adverse effects on the motor activity of the exploratory behaviour in male mice. PMID- 8212058 TI - Change of polyamine level in various tissues of male rats intoxicated with paraquat. AB - The effects of paraquat (PQ) on the contents of putrescine (PUT), spermidine (SPD) and spermine (SPM) in the various tissues and organs were examined by means of high-performance liquid chromatography in rats intoxicated with the toxin by three intraperitoneal infusions of PQ for 6 days on every other day. The contents of PUT, SPD and SPM in the large intestine per mg of wet weight showed statistically significant decreases of 39 (P < 0.01), 73 (P < 0.01) and 27% (P < 0.05), respectively. In the liver, however, they showed statistically significant increases of 214 (P < 0.01), 39 (P < 0.05) and 78% (P < 0.01). PMID- 8212059 TI - Short-term effect of sodium benzoate in F344 rats and B6C3F1 mice. AB - F344 rats and B6C3F1 mice of each sex were administered 0, 1.81, 2.09 or 2.40% (for rats) and 0, 2.08, 2.50 or 3.00% (for mice) of sodium benzoate in the diet for 10 days. In male rats of the 2.4% group, relative liver and kidney weight, serum levels of albumin, total protein and gamma-glutamyl transpeptidase were significantly increased and enlarged hepatocytes with glassy cytoplasm were seen using light microscopy. In male mice of the 3.0% group, absolute liver weights and serum cholesterol and phospholipid levels were significantly increased, and enlargement, vacuolation and necrosis of hepatocytes were evident. PMID- 8212060 TI - Optimization issues in physiological toxicokinetic modeling: a case study with benzene. AB - This paper compares two methods for global optimization of physiologically based toxicokinetic models: Monte Carlo optimization, which searches randomly for the optimum; and the simplex method, which updates systematically an array of parameter values. Two measures of goodness-of-fit are also contrasted: criterion function and likelihood. A 14-parameter model of benzene distribution in rats is used to illustrate these techniques. Simplex optimization yields better fits overall. However, the measurement of uncertainty offered by Monte Carlo simulations is a major argument in favor of their use. PMID- 8212061 TI - Teratogenic evaluation of di-n-butyl phthalate in rats. AB - Pregnant rats were given di-n-butyl phthalate (DBP) by gastric intubation at a dose of 0, 0.5, 0.63, 0.75 or 1.0 g/kg on days 7-15 of pregnancy. A significant decrease in the maternal body weight gain after treatment with DBP was found at a dose of 0.63 g/kg and above. Maternal death and complete resorption of implanted embryos in all the surviving dams were observed in the 1.0 g/kg group. Significantly increased incidence of postimplantation loss and decreased fetal weight were detected at doses of 0.63 and 0.75 g/kg. The incidence of fetuses with malformations was higher in the 0.63 and 0.75 g/kg groups than in the control group, and the difference was significant in the 0.75 g/kg group. Cleft palate were predominantly observed. PMID- 8212063 TI - Biological monitoring of human exposure to atrazine. AB - Atrazine exposure was evaluated in six manufacturing workers by personal and biological monitoring. Total atrazine exposure varied from 10 to 700 mumol per workshift and total urinary atrazine excretion accounted for 1-2% of the external dose. The spectrum of the urinary atrazine metabolites comprises bi-dealkylated (80%), deisopropylated (10%), deethylated (8%) and unmodified atrazine (2%). The metabolites are eliminated in urine in slightly longer than 24 h: 50% of the amount is excreted in the first 8 h following the workshift. PMID- 8212062 TI - 3,3',5-triiodothyronine-induced hepatic respiration: effects of desferrioxamine and allopurinol in the isolated perfused rat liver. AB - The effect of daily doses of 0.1 mg 3,3',5-triiodothyronine (T3)/kg for three consecutive days on hepatic O2 uptake was studied in the isolated perfused rat liver, in the absence and presence of the antioxidants desferrioxamine (DFO) and allopurinol (A). T3 treatment elicited a thermogenic condition in the animals, together with a 25% increase of total O2 consumption by the liver, which is inhibited by 0.5 mM DFO or 1 mM A. The antioxidant-sensitive respiration is enhanced by 62-64% by T3 over control values and represents 16-25% of the net increase in O2 uptake elicited by the hormone treatment. The respiratory components suppressed by the antioxidants are suggested to represent O2 equivalents related to T3-induced oxidative stress, and correlate with elevated rates of fractional lactate dehydrogenase efflux from the perfused livers. PMID- 8212064 TI - Cellular mechanisms of cocaine cardiotoxicity. AB - Although cocaine abuse has been a major drug problem in the United States for over 100 years, it has only been in the last decade that the adverse effects of cocaine on the cardiovascular system have become a serious health issue. The cardiotoxic effects of cocaine are multifactorial and remain a puzzle for investigators to solve. Evidence suggests that cocaine-induced toxic effects on the cardiac and vascular cells include both direct as well as indirect components. In addition, other chemical, physiologic, and environmental factors may further complicate and alter mechanisms and endpoints of cocaine-induced cellular toxicity. In order to fully understand the overall cardiotoxic response to cocaine, the cellular mechanisms and endpoints of toxicity of each of these potentially injurious factors must be identified. PMID- 8212065 TI - Evaluation of chloroform cardiotoxicity utilizing a modified isolated rat cardiac myocytes. AB - An improved technique for the isolation of cardiac myocytes from adult rat is described. This method produced a high yield of isolated cardiomyocytes (30-35 x 10(6) cells/heart) with viability over 88%. The rod-shaped cells represented about 70% of the viable cardiac myocytes. The leakage of creatine phosphokinase (CPK) in the incubation medium from the control was about 37% at zero time. This model was used to investigate chloroform (CHCl3) cardiotoxicity by measuring dye exclusion, change the viable cardiac myocytes shape and CPK leakage. As a result of CHCl3 exposure, there was a significant decrease in Trypan blue exclusion after 30 min and during the entire time course. The percentage of rod-shaped cells decreased significantly during the whole period of the study. Also, a significant elevation in CPK leakage after treatment with 1000 ppm CHCl3 was observed. The data show that the present technique for cardiomyocytes isolation from adult rats produced high percentage of viable cells. Furthermore, the toxic effect of CHCl3 on cardiac myocytes was time dependent. PMID- 8212066 TI - A large dose of ergocalciferol does not cause deficient blood coagulation but is extremely toxic to rats. AB - Male Jcl:SD rats were fed vitamin D2 (ergocalciferol) at levels of 0 (control), 0.39, 0.63 and 1.00% or 0 (control), 0.0195, 0.0315 and 0.050% in the diet for 7 days. All rats of the 0.39-1.00% groups expired on days 2 and 3, while some rats of the 0.0195-0.050% groups died on days 3-6. LD50 (median lethal 7-day cumulative dose calculated from food intake) is 110.5 mg/kg (0.0354% dietarily). In expired and surviving treated rats, several organs (kidney, heart, etc.) were found to be mineralized; there were also renal tubular injuries and pulmonary bleeding. Centrilobular necrosis of liver was detected only in dead rats. Treatment also caused hypercalcemia but did not decrease blood coagulation factors. These results suggest that vitamin D does not have the effect of impeding blood coagulation but that it is extremely toxic, probably due to the hypercalcemia it causes. PMID- 8212067 TI - Aminoguanidine inhibits cell proliferation by prolongation of the mitotic phase. AB - Aminoguanidine has been reported to increase mitotic cells in the liver and to retard the development in chick embryos. In this study, in vitro effects of aminoguanidine on mammalian cells, BRL-3A (from normal rat liver) and HeLa-S3 (from human cervical cancer), were examined. When cells were incubated with varying concentrations of aminoguanidine for 48 h, the cell growth was inhibited at high concentrations of aminoguanidine, without cell death; the 50% growth inhibitory concentrations (IC50) against BRL-3A and HeLa-S3 cells were 4.6 and 2.2 mg/ml, respectively. After culture with aminoguanidine for 24 h, the proportion in the G2/M-phase in both cell lines was increased, but the proportion in the G1-phase was decreased, and the rate in the S-phase was slightly increased at low concentrations of this agent and decreased at high concentrations. The effects of aminoguanidine on the increase in the G2/M-phase in HeLa cells were dose-dependent. In synchronized HeLa cells, aminoguanidine clearly prolonged the M-phase. From these results, it is confirmed that aminoguanidine inhibits cell proliferation by prolonging the M-phase in the cell cycle in mammalian cells as well as chick embryo liver cells. PMID- 8212068 TI - Induction of hepatic drug metabolizing enzymes and interaction with carbon tetrachloride in rats after a single oral exposure to atrazine. AB - A single oral dose (430 mg/kg) of atrazine, a widely employed s-triazine herbicide, was administered to young male rats. There was a significant increase of the in vivo elimination of hexobarbital and a significant induction of the activity of 7-pentoxyresorufin-O-dealkylase, while cytochrome P-450 content and other mixed function oxidase activities remained unaltered. The administration of carbon tetrachloride (CCl4) to atrazine pretreated rats did not substantially augment the impairment of drug metabolizing enzymes brought about by CCl4 alone. Results suggest that atrazine behaves like a relatively weak inducer of phenobarbital-inducible families of cytochrome P-450. PMID- 8212069 TI - The toxicity of chlorophenols in V79 Chinese hamster cells. AB - The toxicity of nine chlorophenols to V79 Chinese hamster cells was determined in a survival assay which gives a direct measure of reproductive cell death by measuring single-cell cloning efficiency. Quantitative analyses of the structure activity relationships showed that the toxicity was linearly related not only to hydrophobicity, as suggested by previous mammalian-cell studies, but also to electronic (electron-withdrawing) substituent effects. The extent electronic factors were related to the toxicity was assessed apart from their influence on partition and transport. The results suggest a relationship between the toxicity and the well-known ability of chlorophenols to induce proton permeability in membranes. PMID- 8212070 TI - Radiolabeled steroidal estrogens in cancer research. AB - It has now been more than 30 years since the laboratory verification of the localization of estrogen in certain animal tissues. Much has been learned since that time regarding the details of this process, including the presence of specific receptors for these hormones in target tissues, the mechanism of ligand binding, the association of the ligand-receptor complex with unique chromatin sequences, and the activation of transcription. A concrete use of this knowledge has been the exploitation of these receptors as a targeting mechanisms for radiopharmaceuticals. This is an exciting area that encompasses both diagnosis and therapy. This review will summarize the in vitro and in vivo data obtained from evaluation of the many compounds that have been examined as radiolabeled receptor ligands, and will also discuss the chemistry necessary for their preparation. In particular, relative binding affinity values for relevant compounds will be tabulated, grouped according to molecular class. For those materials for which biodistributions have been performed, uterine (target), liver (nontarget, clearance), and, when available, tumor tissue uptake values are presented. These data should provide a reminder of what has been accomplished, and should serve as a working reference for those engaged in the pursuit of new candidates for these applications. PMID- 8212071 TI - 17O nuclear magnetic resonance spectra of steroids. AB - The 17O NMR spectra of cholesterol and 31 other steroid alcohols, esters, ketones, and acids enriched by synthesis with 17O from H2(17)O have been observed under ordinary operating conditions, and correlations between 17O chemical shift and structure have been adduced. Spectra-structure correlations for these steroids are in conformity with those previously adduced with simpler compounds by others. PMID- 8212072 TI - Preliminary assessment of luteolin as an affinity ligand for type II estrogen- binding sites in rat uterine nuclear extracts. AB - Naturally occurring bioflavonoids such as luteolin compete for [3H]estradiol binding to nuclear type II sites and mimic methyl p-hydroxyphenyllactate (MeHPLA) as ligands for this cell regulatory protein. More importantly, luteolin (3',4',5,7-tetrahydroxyflavone) contains catechol hydroxyl groups on the A and B rings that may form quinones capable of binding covalently to proteins; therefore, we evaluated luteolin as a potential affinity ligand for rat uterine nuclear type II sites. The preliminary experiments presented in this manuscript demonstrate that luteolin and a related bioflavonoid, 4,7-dihydroxyflavone (DHF), are competitive inhibitors of [3H]estradiol binding to type II sites in ammonium sulfate (AmSO4) extracts of rat uterine nuclei. This high affinity (Kd 5-10 nM) interaction is specific for type II sites, and neither compound binds to the estrogen receptor (ER). More importantly, the interaction of luteolin with nuclear type II sites was irreversible, whereas DHF readily exchanged with [3H]estradiol for type II sites in these preparations. These findings suggest that this nonexchangable occupancy of type II sites by luteolin is likely to involve covalent attachment. Spectrophotometric analysis of type II site preparations pretreated with luteolin also confirmed the [3H]estradiol exchange assay data, demonstrating that the ligand attachment is irreversible. Because luteolin did not affect [3H]estradiol binding to the ER in uterine cytosol, we suspect that this bioflavonoid may not be simply randomly interacting with a multiplicity of proteins to generate covalent complexes. These preliminary findings suggest that high-affinity binding of luteolin by type II sites is prerequisite to covalent attachment and that this bioflavonoid may be a suitable affinity ligand for the purification of this protein. PMID- 8212073 TI - Decreased cortisol-binding affinity of transcortin Leuven is associated with an amino acid substitution at residue-93. AB - Genomic DNA was isolated from two related individuals who are homozygous for transcortin Leuven, a corticosteroid-binding globulin variant with decreased cortisol-binding affinity. This material was amplified using intron-specific oligonucleotide primers in a polymerase chain reaction to obtain the four exons that encode transcortin. Sequence analysis of these exons showed several mutations within the coding sequence of both individuals, but only one of these will result in an amino acid substitution. This mutation is located within exon 2 and alters the codon (CTC) normally associated with Leu-93 in the transcortin polypeptide to a codon (CAC) for histidine in the variant genes. PMID- 8212074 TI - Two novel microbial conversion products of progesterone derivatives. AB - Two novel microbial steroid hydroxylations were found in a screening of 131 microorganisms under aerobic conditions. 17 alpha-Hydroxyprogesterone was hydroxylated in the 8 beta-position by Corynespora melonis CBS 16260, and fermentation of 17 alpha-acetoxyprogesterone with Pycnosporium species ATCC 12231 yielded 11 beta-hydroxy- and 11 beta, 12 beta-dihydroxy-17 alpha acetoxyprogesterone. The known 11 beta-hydroxy compound could be obtained as a single product with Trichothecium roseum ATCC 12519. PMID- 8212075 TI - Formation of 18-deoxy-19-noraldosterone by a human aldosterone-producing adenoma. AB - The recently synthesized 18-deoxy-19-noraldosterone is a potent aldosterone antagonist. In the present study we demonstrate the in vitro formation of 18 deoxy-19-noraldosterone from 19-noraldosterone in a human aldosterone-producing adenoma and normal adrenal tissue. The metabolite was isopolar, cochromatographed with the authentic standard on high-performance liquid chromatography, and the identity was further analyzed by mass spectrometry. The possible role of 18-deoxy 19-noraldosterone in primary aldosteronism is also discussed. PMID- 8212076 TI - Relationship of serum sex hormones to coronary heart disease . PMID- 8212077 TI - Genistein is an effective stimulator of sex hormone-binding globulin production in hepatocarcinoma human liver cancer cells and suppresses proliferation of these cells in culture. AB - Studies have indicated a correlation between a high level of urinary lignans and isoflavonoid phytoestrogens, particularly genistein, and a low incidence of hormone-dependent cancers, such as breast and prostate cancer. Previously it has been observed that a vegetarian diet is associated with high plasma levels of sex hormone-binding globulin (SHBG), reducing clearance of sex hormones and probably risk of breast and prostate cancer. In the present study we investigated the in vitro effect of genistein on the production of SHBG by human hepatocarcinoma (Hep G2) cells in culture and its effect on cell proliferation. We found that genistein not only highly significantly increases the SHBG production by Hep-G2 cells, but also suppresses the proliferation of these cancer cells already at a stage when SHBG production continues to be high. We conclude that, in addition to the lignan enterolactone, the most abundant urinary isoflavonoid genistein stimulates SHBG production and inhibits Hep-G2 cancer cell proliferation. PMID- 8212078 TI - Aldosterone secretion and the mechanism of potassium adaptation in rats. AB - In order to better understand the cellular mechanism of potassium (K+) adaptation, the sensitivity of aldosterone secretion to acute changes in extracellular K+ concentration was studied in freshly dissected adrenal capsules of rats adapted to diets of high or low K+ content, of rats adapted to low or high sodium (Na+) diets, and also of control rats. In control tissues, the aldosterone secretion from the capsules of an individual animal averages 0.44 +/- 0.05 nmol/h, increasing 4.4-fold between 2 and 8 mM K+ but decreasing between 8 and 10 mM K+. Although a high K+ diet increases aldosterone secretion by only 34% at 4 mM K+, the rate of secretion increases 3.7-fold more steeply than control as the K+ concentration increases. This change is equivalent to a parallel 3.1-fold increase in the effective number of T- and L-type calcium (Ca2+) channels, accompanied by a 1.3-fold increase in the K(+)-insensitive rate of aldosterone secretion. In contrast, after Na+ restriction, aldosterone secretion is about 3 times the control rate for all K+ concentrations tested, equivalent to an increase in the basal rate and the effective number of L-channels. Thus, the alteration in the number of effective T-channels is specific to diets of increased K+ content, not simply an effect of increased secretory capacity. After a low K+ diet, aldosterone secretion is 18% of control at 4 mM K+ and changes little with the K+ concentration, consistent with a 94% to 96% decrease in the effective number of T- and L-channels plus a 77% decrease in the K(+)-insensitive rate of aldosterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212079 TI - Hydroxylation of the native brassinosteroids 24-epicastasterone and 24 epibrassinolide by the fungus Cunninghamella echinulata. AB - 24-Epicastasterone and 24-epibrassinolide, two naturally occurring phytohormones of the brassinosteroid type, were transformed by the fungus Cunninghamella echinulata to give the corresponding 12 beta-hydroxylated compounds. The structures of these compounds were determined by spectroscopic methods, especially heterocorrelated two-dimensional nuclear magnetic resonance investigations. In the rice lamina inclination test the 12 beta-hydroxylation lowered the bioactivity at 0.1 ppm to 10% in comparison with that of the corresponding parent hormones. The described hydroxylations represent the first biotransformations of native brassinosteroids. PMID- 8212080 TI - Determination of follicular fluid estradiol levels by enzyme-linked immunosorbent assay. AB - A direct competitive heterologous enzyme-linked immunosorbent assay (ELISA) was developed and validated to determine follicular fluid estradiol levels of different antral follicular sizes (small, medium, and large) obtained from the ovaries of heifers in the follicular phase of the estrous cycle. Polyclonal antiestradiol antibodies were raised in New Zealand White rabbits using 6-keto 1,3,5(10)-estratriene-3,17 beta-diol 6-carboxymethyloxime: bovine serum albumin as immunogen and characterized by the usual methods. Horseradish peroxidase conjugated to 1,3,5(10)-estratriene-3,17 beta-diol 3-hemisuccinate was used as a label. The concentration range used for the standard curve was 0 to 1 ng per well. The low detection limit of the technique was 0.3 pg per well with a sensitivity at 50% binding of 93.62 pg per well. Intraassay and interassay CV (%) were < 5.3% and < 7.0%, respectively (n = 10). The recovery rate of the known estradiol concentrations added to follicular fluid averaged 96.1 +/- 1.3%. Compared with a radioimmunoassay (RIA), the values of ELISA were highly correlated (r = 0.99, P < 0.005). This assay was used to quantify follicular fluid estradiol concentrations without previous extraction in three antral follicular sizes; small (< 5 mm), medium (5.1 to 10 mm), and large (10.1 to 20 mm). The mean +/- SE follicular fluid estradiol concentrations were 77 +/- 5.2 ng/ml (n = 490) in small follicles, 111 +/- 19 ng/ml (n = 65) in medium follicles, and 496 +/- 144 ng/ml (n = 45) in large follicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212081 TI - Labeling of estradiol and testosterone alkyloxime derivatives with a europium chelate for time-resolved fluoroimmunoassays. AB - O-Carboxymethyl, O-(4aminobutyl)-, and O-(6-aminohexyl)-oximes of 6-oxoestradiol and testosterone were labeled using a described general labeling method with a europium chelate. A stable amide or thiourea bond was formed between the europium label and carboxyl or amino derivative of the steroid, respectively. These labeled "tracers" were purified and briefly tested in a competitive time-resolved fluoroimmunoassay using monoclonal antibodies raised against O (carboxymethyloxime)-bovine serum albumin derivatives of estradiol and testosterone. Only buffer-based standards were used in a model system for the testing. These studies indicate only minor functional differences while using these antibodies due to the length of the spacer arm, and a higher sensitivity in the clinically relevant standard range was reached with the longer spacers. PMID- 8212082 TI - Stimulatory effect of 1,25-dihydroxyvitamin D3 on calcium handling and insulin secretion by islets from vitamin D3-deficient rats. AB - Among the various vitamin D3 metabolites, 1,25-(OH)2D3 is the specific secosteroid hormone that can enhance, in vitro, the weak insulin response to glucose of islets from vitamin D3-deficient rats. Because this potentiating effect is preceded by an increase in Ca2+ handling, several putative sites of action were studied by measuring 45Ca2+ and 86Rb+ (as K+ tracer) efflux during perifusions in the presence of various stimuli known to affect Ca2+ movements in different ways: high glucose without calcium, high calcium without glucose, high potassium, or barium-theophylline without calcium or glucose. The present results show that 1,25-(OH)2D3 may activate Ca2+ handling by at least two mechanisms: (1) an increase of Ca2+ entry via voltage-dependent Ca2+ channels in the experiments in which extracellular Ca2+ was present and where Ca2+ channels were opened; this 1,25-(OH)2D3 influence on Ca2+ channels was not mediated by a possible indirect influence on K+ channels because 86Rb+ fluxes were never observed to be affected by the steroid; (2) an enhancement of 45Ca2+ mobilization from intracellular stores as suggested by barium-theophylline stimulation and probably also via the Ca2+ stimulus. Both of these 1,25-(OH)2D3 influences tended to provide more calcium to the B cell of vitamin D3-deficient rats. But this prerequisite was not sufficient in itself to potentiate the insulin response; indeed, experiments with barium-theophylline suggested that 1,25-(OH)2D3 may also activate a cAMP dependent exocytosis process. PMID- 8212083 TI - Endogenous testosterone and competition: the effect of "fasting". AB - Salivary testosterone was measured among male college wrestlers (n = 12), some of whom fasted before their matches while others did not. Nonfasting wrestlers had increasing testosterone on the day of their match, whereas fasting wrestlers had decreasing testosterone. Apparently, fasting perturbs the normal pattern of testosterone fluctuation associated with competition. As used here, the term "fasting" does not necessarily imply 100% abstinence from nourishment. PMID- 8212084 TI - Synthesis and 29-14C-labeling of 3 alpha, 7 alpha, 12 alpha-trihydroxy-27 carboxymethyl-5 beta-cholestan-26-oic acid. A bile acid occurring in peroxisomal diseases. AB - The synthesis and 14C-labeling of 3 alpha, 7 alpha, 12 alpha-trihydroxy-27 carboxymethyl-5 beta-cholestan-26-oic acid by two different approaches is described. One of them involves chain elongation of cholic acid via Wittig-Horner condensation of its formylated 24-aldehyde with tetraethyl phosphonoglutarate. The resulting cholestenoate, on deprotection and hydrogenation, affords the unusual C29 bile acid in good yield. An alternative procedure consists in a malonic ester synthesis starting from the formylated 24-alcohol which, after conversion into a mesylate, is reacted with sodium salt of 2-carboethoxy-gamma butyrolactone. Alkaline hydrolysis, decarboxylation, esterification with diazomethane and selective tosylation of the newly introduced primary hydroxyl function give a C28 precursor, which is easily chain-elongated into a labeled or unlabeled C29 bile acid by reaction with cyanide and hydrolysis. Due to the easy lactonization of some of the C28 intermediates, the latter method provides a better way for introducing a C-29 label than the sequence usually employed for carboxyl labeling of bile acids and consisting in a decarboxylative halogenation of the parent acid followed by substitution of the norhalogenide with [14C]cyanide and hydrolysis. The structure of the synthesized acid or its dimethyl ester is confirmed by 13C nuclear magnetic resonance spectroscopy and mass spectrometry, and is also shown by gas liquid chromatography to be identified with an authentic sample of biosynthetic C29 dioic bile acid extracted from body fluids of Zellweger patients. PMID- 8212086 TI - Potential bile acid metabolites. 20. A new synthetic route to stereoisomeric 3,6 dihydroxy- and 6-hydroxy-5 alpha-cholanoic acids. AB - An improved procedure for the syntheses of stereoisomeric 3,6-dihydroxy- and 6 hydroxy-5 alpha-cholanoic acids (and their methyl esters) is described. The principal reactions employed are those reported in the preceding paper of this series, with the commercially available hyodeoxycholic acid as starting material. The final step in the procedure is the reduction of the key 5 alpha C-6 ketones with either the stereoselective equatorial reagent, Li/NH3/MeOH, or the axial reagent, Zn(BH4)2. The results of analysis of the prepared 6-monohydroxylated and 3,6-dihydroxylated stereoisomers by thin-layer chromatographic, high performance liquid chromatographic and gas-liquid chromatographic mobilities, and 1H and 13C nuclear magnetic resonance spectra are discussed along with the data for the corresponding compounds in the 5 beta-series. PMID- 8212085 TI - Unsaturated fatty acid modulation of glucocorticoid receptor binding in L2 cells. AB - Glucocorticoids stimulate fatty acid synthesis during late fetal lung development by inducing fatty acid synthetase. To determine whether fatty acids modulate glucocorticoid receptor binding, we investigated the in vitro effect of fatty acids on [3H]triamcinolone acetonide (TA) binding to the cytosolic glucocorticoid receptor in L2 cells, a cell line cloned from the adult rat type II cell. The L2 cell glucocorticoid receptor exhibited specific binding of [3H]TA which was saturable and appeared to be a single species of binding sites with an apparent KD = 4.9 +/- 3.7 nM and Bmax = 395.4 +/- 84.4 fmol/mg protein. The receptor had the ligand specificity typical of a physiologically relevant glucocorticoid receptor. Long-chain unsaturated fatty acids (oleic acid [18:1], linoleic acid [18:2], and arachidonic acid [20:4]) markedly inhibited [3H]TA specific binding in a dose-dependent manner, but long-chain saturated fatty acids (myristic, 14:0; palmitic, 16:0; and stearic acid, 18:0) and phospholipids had no effect. Scatchard analysis revealed a noncompetitive type of inhibition by unsaturated fatty acids. This suggests that unsaturated fatty acids modulate L2 cell glucocorticoid receptor by binding to sites different from the glucocorticoid binding sites in the receptor. We propose that unsaturated fatty acids may act as negative feedback modulators of glucocorticoid-receptor binding in the lung. PMID- 8212087 TI - Structure of the novel steroidal antibiotic squalamine determined by two dimensional NMR spectroscopy. AB - Squalamine is a novel aminosterol recently isolated from the dogfish shark, Squalus acanthias. This water-soluble steroid exhibits potent antibacterial activity against both gram-negative and gram-positive bacteria. In addition, squalamine is fungicidal and induces osmotic lysis of protozoa. We report here the structural determination of squalamine, 3 beta-N-1-[N(3-[4-aminobutyl])-1,3 diaminopropane]-7 alpha,24 zeta-dihydroxy-5 alpha-cholestane 24-sulfate, which was deduced from the analysis of fast atom bombardment spectra and a series of two-dimensional nuclear magnetic resonance (NMR) spectra. Squalamine is a cationic steroid characterized by a condensation of an anionic bile salt intermediate with the polyamine, spermidine. This molecule is a potential host defense agent in the shark, and provides insight into a new class of vertebrate antimicrobial molecules. PMID- 8212088 TI - Steroidogenesis in sheep ovarian antral follicles in culture: time course study and supplementation with a precursor. AB - The present study was designed to explore the steroidogenic responsiveness of ovine antral follicles of different sizes when cultured for varying time-periods with different doses of pregnenolone. Antral follicles of different sizes were isolated from sheep ovaries and cultured in medium 199 with or without pregnenolone in the presence or absence of FSH for 1, 6, 10, and 24 hours at 37 C. The levels of progesterone and estradiol in the spent medium were estimated. In the absence of pregnenolone, steroid production by the follicles did not increase significantly beyond 1 hour of culture. However, in the presence of pregnenolone there was a significant increase in progesterone production at 6, 10, and 24 hours of culture compared to controls. Estradiol levels were unaffected. Addition of FSH in combination with pregnenolone failed to increase progesterone or estradiol levels beyond that seen with pregnenolone alone. These data demonstrate that short-term incubation of follicles is sufficient for the secretion of steroids into the culture medium and supplementation of the culture medium with an immediate precursor is essential for optimal steroidogenesis in vitro. PMID- 8212089 TI - Stimulation of aldosterone production by hemin in calf adrenal glomerulosa cell cultures. AB - Aldosterone production from 11-deoxycorticosterone was stimulated by hemin in primary cultures and homogenates of calf adrenal zona glomerulosa, in a time- and dose-dependent fashion. The ferrochelatase inhibitor 3,5-diethoxycarbonyl-1,4 dihydro-2,4,6-trimethylpyridine (DDC) blocked the stimulation of aldosterone mediated by adrenocorticotropin (ACTH). Addition of hemin after treatment with DDC partially restored ACTH action. These results suggest that hemin may play a role in regulation of aldosterone production. PMID- 8212090 TI - Epi-sarsasapogenin and epi-smilagenin: two sapogenins isolated from the rumen content of sheep intoxicated by Brachiaria decumbens. AB - Spectroscopic examination of purified extracts of the rumen content of sheep intoxicated by Brachiaria decumbens revealed the presence of two spirostanes, identified as epi-sarsasapogenin and epi-smilagenin. Sarsasapogenone was obtained by the oxidation of sarsasapogenin. The reduction of sarsasapogenone using lithium aluminum hydride yielded isomeric products, sarsasapogenin (20%) and epi sarsasapogenin (80%). PMID- 8212091 TI - The clandestine epidemic: the practice of unsafe abortion in Latin America. AB - In Latin America, induced abortion is the fourth most commonly used method of fertility regulation. Estimates of the number of induced abortions performed each year in Latin America range from 2.7 to 7.4 million, or from 10 to 27 percent of all abortions performed in the developing world. Because of restrictive laws, nearly all of these abortions, except for those performed in Barbados, Belize, and Cuba, are clandestine and unsafe, and their sequelae are the principal cause of death among women of reproductive age. One of every three to five unsafe abortions leads to hospitalization, resulting in inordinate consumption of scarce and costly health-system resources. Increased contraceptive prevalence and restrictive abortion laws have not decreased clandestine practices. This article addresses how the epidemic of unsafe abortion might be challenged. Recommendations include providing safer outpatient treatment and strengthening family planning programs to improve women's contraceptive use and their access to information and to safe pregnancy termination procedures. In addition, existing laws and policies governing legal abortion can be applied to their fullest extent, indications for legal abortion can be more broadly interpreted, and legal constraints on abortion practices can be officially relaxed. PMID- 8212092 TI - Contraceptive knowledge, attitudes, and practice in Russia during the 1980s. AB - In the former Soviet Union, there was a lack of valid and reliable social research on knowledge, attitudes, and practice of contraception. The few available studies have not been published outside the Soviet Union. This article reviews five surveys that were conducted in Moscow and two other cities (Saratov and Tartu) during the period 1976-84. In addition, some data from a large-scale survey conducted in 1990 and covering the entire former Soviet Union are presented. The surveys indicate that the rhythm method, condoms, vaginal douches, and withdrawal were the main contraceptive methods used; only 1 to 3 percent of the women interviewed were using oral contraceptives, and about 10 percent used intrauterine devices. The low prevalence of use of reliable modern methods may explain the high incidence of induced abortion in Russia. The chronic unavailability of reliable contraceptives is one of the main factors of poor family planning. Lack of knowledge and negative opinions about modern contraception also play an important role. Some possibilities for improving the family planning situation in Russia are discussed. PMID- 8212093 TI - The Brazilian experience with Cytotec. AB - Cytotec, the commercial name for misoprostol, which is a synthetic analogue of prostaglandin E1, was approved for use in Brazil in 1986 to treat gastric and duodenal ulcers. The drug can and has also been used to induce abortion, which has created controversy in a country in which induced abortion is illegal. A study of the drug was undertaken in 1992 that included analyses of the drug's sales profile, of information published by the media, and of its use from women's and gynecologists' points of view, the latter examined using qualitative methodologies. The analysis of Cytotec's sales volume showed quick growth from its introduction until the first half of 1991, when its use was restricted by the Ministry of Health. For women, Cytotec's main advantages have been that it is relatively inexpensive, convenient to use, and can be used in private. Data obtained from gynecologists show that Cytotec's addition to the obstetric therapeutic arsenal was welcome and also confirmed the drug's influence in reducing the complications of illegal abortions shown in other studies. PMID- 8212094 TI - Induced abortion in Indonesia. AB - Induced abortion is one of the most difficult sociomedical problems facing the Indonesian government. While well-known in traditional society, the practice was discouraged by all Indonesian religious groups, and forbidden by the Dutch colonial authorities. Although abortion was technically illegal under the criminal code, a judicial interpretation in the early 1970s permitted medical professionals to offer the procedure so long as they were discreet and careful. The numbers of medical abortions carried out in Indonesia rose dramatically, and there was evidence of matching declines in the incidence of morbidity and mortality caused by dangerous illegal procedures. Medical and community groups campaigned for a more liberal abortion law to protect legal practitioners and stamp out illegal traditional practices. Their efforts appeared to bear fruit in the draft Health Law, but when the law was passed by the legislature in late 1992, the issue was again clouded by contradictions and inconsistencies. PMID- 8212095 TI - Using self-assessment to improve the quality of family planning clinic services. AB - A follow-up study was conducted to evaluate the effect of a self-assessment technique called COPE (client-oriented, provider-efficient) on the quality of family planning clinic operations in Africa. In 1991 the Association for Voluntary Surgical Contraception revisited 11 clinics where it had introduced COPE from five to 15 months earlier. Changes that had occurred as a result of the COPE intervention were assessed by (1) determining how many of the clinic problems identified by staff at the COPE introduction had been solved; (2) comparing the results of a second client-flow analysis with the initial analysis; and (3) interviewing service providers to obtain their opinions of the effects of COPE. Of the problems identified by staff nearly three-fourths of those that could be solved internally were solved. The study revealed improvements in the quality of care provided as well as increased staff involvement in solving clinic problems. PMID- 8212096 TI - Zambia 1992: results from the Demographic and Health Survey. PMID- 8212097 TI - Environmental control: operating room air quality. AB - 1. OR staff members should familiarize themselves with basic air handling system terminology to better manage their own environment (eg, HVAC, air changes, air balancing, HEPA filtration). A working relationship with building engineers is an important skill for the OR nurse. 2. Knowledge of the standards on which air quality in the OR is based should assist in the process of planning for improved design--as well as in monitoring existing air quality. 3. Current standards balance energy savings with air changes and high levels of filtration to achieve optimum outcomes. Recommendations from design and engineering authorities (even for implant surgery) are based on average air changes and HEPA filtration, not laminar air flow. 4. The daily, operational role of the OR staff in maintaining high air quality includes managing traffic, using low-lint barrier materials, monitoring air quality indicators, and investigating unusual variances with the engineering staff for appropriate follow-up (eg, filter changes). PMID- 8212098 TI - Postoperative pneumonia. AB - 1. Postoperative nosocomial (hospital-associated) pneumonia is among the most serious complications of surgery. The mortality from these pneumonias is 30%, even with treatment with appropriate antibiotics. 2. The incidence of pneumonia in patients on ventilators averages 14 times that of patients not receiving mechanical ventilator support. These pneumonias are a major factor in the deaths of patients using ventilators. The design and necessary functions of ventilators contribute to bacterial colonization of the machinery, airway, and lungs. Burn patients also represent a particularly vulnerable group in relation to nosocomial pneumonia. 3. Health care workers can introduce organisms from the environment or the patient in the next bed by neglecting handwashing between patients. Some health care professionals think it is not necessary to change the gloves that protect them from bloodborne pathogens when moving between patients. Such erroneous beliefs add significantly to the patient's bacterial colonization, often with treatment-resistant organisms. PMID- 8212099 TI - Tuberculosis comeback: what you need to know. AB - 1. The number of tuberculosis (TB) cases in the United States has ceased to decline and is rising in some areas of the country. This means that the likelihood of caring for a patient with TB is greater. 2. To handle patients with TB, the epidemiology, transmission, pathogenesis, infectiousness, and treatment of tuberculosis must be understood. 3. TB should be considered in any patient who has a persistent cough or other general symptoms of weight loss, fever, anorexia, and night sweats. PMID- 8212100 TI - A tuberculosis outbreak from a patient's draining lesion: how did it happen? AB - 1. Mycobacterium tuberculosis can be transmitted from a pulmonary source when droplet nuclei in the 1 to 5 micron range are generated by coughing, singing, or even talking. 2. It is possible for large numbers of droplet nuclei containing M tuberculosis bacteria to be generated during the surgical drainage, debridement, and syringe irrigation of abscesses caused by M tuberculosis. These procedures can produce such a high concentration of droplet nuclei that the ventilation system cannot remove them fast enough to protect the surgical staff from infection. 3. The unrecognized case of tuberculosis is much more likely to be the source of transmission of M tuberculosis than is the individual who has a diagnosis of TB or "rule-out TB." This is because once a diagnosis is known or suspected, interventions are initiated that make the patient less infectious. PMID- 8212101 TI - Surgical blood exposures after the OSHA bloodborne pathogens standard: frequency and prevention. AB - 1. Approximately 22.4 million surgical procedures are performed annually in US hospitals. Up to 2,688,000 personnel exposures to blood may occur annually. Punctures would account for 349,940 (13%) of those exposures, and 38,493 patients would have contact with blood from the punctured personnel. 2. Epidemiologists use parameters of time, place, and person to describe situations and identify prevention strategies: who is at increased risk, what devices and activities lead to more frequent exposures, when exposure frequency is greatest, and where blood contact actually occurs. The answers to these questions form the basis for successful prevention; without the correct answers operating rooms either miss the target or spend far too much money preventing low-risk events. 3. OSHA and previous researchers estimated that a substantial portion of blood exposures could be prevented by either changing certain practices such as passing loaded suture holders, or by protective attire such as fluid-resistant gowns. PMID- 8212102 TI - Medical waste: reducing its generation. AB - 1. Materials that can be recycled have yet to be proven to be a more cost effective means of reducing medical waste. The literature indicates that the efficacy of reusable textiles is at least equal to that of some disposables--and reusable items reduce the generation of blood-contaminated waste. 2. The perioperative nursing community should consider replacing single-use items with materials intended for multiple uses. 3. "Source reduction" entails the replacement of single-use items with reusable items. Successful source-reduction programs require changes in individual and collective behavior patterns. 4. Recycling of materials renders them suitable for another use in a product similar to that in which they were originally used. On the other hand, reprocessing is an all-descriptive term of what must be done to an item to render it suitable for another identical use. PMID- 8212103 TI - Responding to irritable people in the OR setting. AB - 1. Irritability may be caused by psychologic factors, physiologic factors, external factors, or a combination of factors. 2. If the nurse reacts to another individual's irritability by feeling inadequate, becoming irritable, or any other number of nontherapeutic responses, emotions may be escalated, interpersonal relationships may be irretrievably damaged, and productivity on the job may be diminished. 3. A therapeutic response to irritability can have a steadying effect and lead to a peaceful resolution; appropriate response by the nurse to facilitate positive communication, provide support, and promote effective resolution of problems can assist in pacifying tense situations when irritability becomes a problem. PMID- 8212104 TI - A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 2. Mortality and morbidity from malaria in the study area. AB - Background data on child mortality and morbidity from malaria were obtained in a new study area in the centre of The Gambia, south of the river, chosen as the site for a malaria intervention trial. Infant and child mortality rates were 120 and 41 per 1000 respectively. Results obtained using post-mortem questionnaires suggested that malaria was an uncommon cause of death in children under the age of one year but responsible for about 40% of deaths in children aged 1-4 years. Ninety-two percent of deaths attributed to malaria occurred during or immediately after the rainy season. Parasite and spleen rates in children aged 1-5 years at the end of the malaria transmission season were 66% and 64% respectively. Malariometric indices were similar in primary health care (PHC) villages, selected as sites for an intervention with insecticide-treated bed nets and targeted chemoprophylaxis, and in smaller, non-PHC, control villages. PMID- 8212105 TI - A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 3. Entomological characteristics of the study area. AB - Baseline entomological surveillance was carried out in a rural area of The Gambia during the rainy season in 1988, one year before the implementation of a malaria control programme using insecticide-impregnated nets and targeted chemoprophylaxis in villages with a primary health care (PHC) system. Mosquito collections took place in 6 pairs of settlements each with untreated bed nets; within each pair there was a large PHC village with a resident village health worker (VHW) and traditional birth attendant (TBA) and a smaller non-PHC village without either a VHW or a TBA. The most common vectors in the study area were Anopheles gambiae sensu stricto and, to a lesser extent, An. arabiensis. These mosquitoes were found in appreciable numbers for at least 4 months of the year (geometric mean/bedroom/night = 32.5, 95% confidence interval 18.2-57.3). Numbers of mosquitoes collected in PHC villages or non-PHC villages were not significantly different. Greater numbers of mosquitoes were found in villages closer to the River Gambia than in those further away. Evidence for DDT resistance due to elevated glutathione S-transferase activity was found in one of the 12 villages, but there was no evidence of resistance to organophosphate or carbamate insecticides as suggested by the low esterase levels and carbamate sensitive acetylcholinesterase. PMID- 8212106 TI - A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 4. Perceptions of the causes of malaria and of its treatment and prevention in the study area. AB - Perceptions of the causes of malaria, its treatment and prevention were studied among 996 adults, selected randomly from 73 villages and hamlets in a rural area of The Gambia. Structured questionnaires and other interview techniques were used for data collection. Malaria has no specific name in the study area; it is referred to commonly as Fula kajewo (Fula fever). Only 28% of the respondents knew that mosquitoes transmitted malaria. However, most people believed correctly that August to October was the main malaria season. Eighty-six per cent of the subjects were bed net users. The majority of nets were produced locally, usually white in colour and made of sheeting fabrics. Usage of nets was correlated with ethnic group, age and polygamy but not with education, income, occupation or ownership of certain items which indicate high social status. Analysis of expenditure on mosquito coils indicated that non-users of nets spent 43% more on coils than did users. Bed nets have been used for a long time in the study area; 98% of users saw their parents using them during their childhood. PMID- 8212107 TI - A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 1. A review of the epidemiology and control of malaria in The Gambia, west Africa. AB - Malaria was recognized as an important cause of death among early European visitors to The Gambia, but the infection was first studied systematically in the local population only in the 1950s. Studies undertaken in the village of Keneba at that time showed that nearly all children under the age of 5 years had parasitaemia throughout the year. More recent surveys in rural areas of The Gambia have shown much lower levels of parasitaemia, probably as a result of a decline in rainfall in The Gambia during the past 30 years and because of an increase in the availability of anti-malarial drugs. Nevertheless, community surveys and reviews of hospital statistics show that malaria is still one of the most important causes of death among Gambian children; about 1 in 25 rural Gambian children die from malaria before reaching the age of 5 years. Until recently, malaria control in The Gambia relied upon prompt treatment of clinical attacks, first with quinine and more recently with chloroquine, and upon some limited vector control in the capital, Banjul. However, during the past few years, it has been shown that mortality in rural children can be reduced substantially by means of chemoprophylaxis given by village health workers. Bed nets (mosquito nets) are used widely in The Gambia and epidemiological surveys have shown an association between the use of bed nets and protection against malaria. This observation led to a series of small scale intervention trials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212108 TI - A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 5. Design and implementation of the trial. AB - A large-scale malaria intervention programme using insecticide-treated bed nets and chemoprophylaxis administered to children was introduced into a rural area of The Gambia. The operation was carried out using the existing primary health care (PHC) service in the region. Training of the village health workers, sensitization of the communities, and implementation of net impregnation and the drug delivery programme are described. This delivery system resulted in over 90% of nets being treated with insecticide and 80% of children receiving over 90% of their tablets during the rainy season. There was considerable variation in the distribution of permethrin on a bed net and between individual nets, which is likely to facilitate the spread of insecticide resistance in the local mosquito populations. Bed nets made from heavier fabrics tended to absorb more insecticide than those made from lighter materials. Four months after dipping, 89% of the insecticide had been lost from treated nets. This was probably due mainly to women washing their nets, an activity carried out on average once every 2 months during the rainy season. The high number of insecticide-treated bed nets in the study area demonstrated that a malaria control programme operated through a PHC system can be implemented successfully. PMID- 8212109 TI - A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 6. The impact of the interventions on mortality and morbidity from malaria. AB - The effects of insecticide-impregnated bed nets on mortality and morbidity from malaria have been investigated during one malaria transmission season in a group of rural Gambian children aged 6 months to 5 years. Sleeping under impregnated nets was associated with an overall reduction in mortality of about 60% in children aged 1-4 years. Mortality was not reduced further by chemoprophylaxis with Maloprim given weekly by village health workers throughout the rainy season. Episodes of fever associated with malaria parasitaemia were reduced by 45% among children who slept under impregnated nets. The addition of chemoprophylaxis provided substantial additional benefit against clinical attacks of malaria; 158 episodes were recorded among 946 children who slept under impregnated nets but who also received chemoprophylaxis. Chemoprophylaxis reduced the prevalence of splenomegaly and parasitaemia at the end of the malaria transmission season by 63% and 83% respectively. Thus, insecticide-impregnated bed nets provided significant protection in children against overall mortality, mortality attributed to malaria, clinical attacks of malaria, and malaria infection. The addition of chemoprophylaxis provided substantial additional protection against clinical attacks of malaria and malaria infection but not against death. PMID- 8212111 TI - Transfusion-associated graft-versus-host disease: scratching the surface. PMID- 8212110 TI - A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 8. Cost effectiveness of bed net impregnation alone or combined with chemoprophylaxis in preventing mortality and morbidity from malaria in Gambian children. AB - In The Gambia, insecticide impregnation of bed nets, used alone or combined with Maloprim, reduced morbidity and mortality from malaria amongst children between one and 4 years of age. Taking expenditure of both time and money by public authorities and village volunteers into account, the costs and cost-effectiveness of each intervention were estimated. Bed net impregnation alone and the combined strategy cost US $5.65 and US $7.49 per child-year protected respectively (1990 figures). Insecticide (and drugs) accounted for more than 80% of the costs of each intervention strategy. They were both highly cost-effective. Estimated costs per death and per clinical episode of malaria averted were US $188 and US $28 for bed net impregnation and $257 and $19 for impregnation combined with chemoprophylaxis. Estimated costs per healthy year of life saved, discounted at 3%, were US $7.90 and US $10.84. PMID- 8212112 TI - Meta-analysis of clinical studies: the whole is greater than the sum of its parts. PMID- 8212113 TI - Acute changes in systemic blood pressure and urine output of conscious rats following exchange transfusion with diaspirin-crosslinked hemoglobin solution. AB - This report describes acute changes in systemic blood pressure and urine output observed after a 50-percent isovolemic exchange transfusion (ET) with diaspirin crosslinked hemoglobin (alpha alpha Hb). Stroma-free Hb was crosslinked between the alpha chains by using a 14C-labeled diaspirin, bis(3,5 dibromosalicyl)fumarate. Forty conscious, chronically cannulated rats underwent ET with 14C-labeled alpha alpha Hb solution (8.0 g/dL [80 g/L]). This resulted in systemic hypertension for 3 to 4 hours after ET (mean arterial pressure rose from 120 to 145 torr at 1 to 2 hours after ET) and mild bradycardia for 2 to 3 hours (heart rate decreased from 420 to 335 beats/min [bpm] before stabilizing at 360 +/- 10 bpm). This was accompanied by significant diuresis immediately after ET (5 6-fold increase in urine output, which normalized after 12 hours), and mild hemoglobinuria. The total amount of Hb recovered in the urine was < 5 percent of the injected dose. Reversed-phase high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed the presence of crosslinked alpha alpha Hb molecules in the urine. Renal excretion of radioactivity was significantly greater, with 20 percent of total radioactivity being eliminated within 24 hours. The plasma half-life for alpha alpha Hb was 5 hours (administered dose, 2.4 g Hb/kg body weight). Thus, infusion of alpha alpha Hb caused a transient systemic hypertension, and intramolecular crosslinking alone was not enough to exclude completely the filtration of alpha alpha Hb by the kidneys. PMID- 8212114 TI - In vivo viability studies of two additive solutions in the postthaw preservation of red cells held for 3 weeks at 4 degrees C. AB - An optimized additive solution was developed for the postthaw preservation of red cells that contained adenine, glucose, disodium phosphate, and citrate buffer. This solution, called AS-17, was compared to AS-3 solution in a clinical trial using 40 subjects (20 in each arm). Fresh-frozen red cells were thawed and deglycerolized after 1 to 18 months and subjected to a second period of storage in either solution for up to 3 weeks at refrigerator temperatures. Both solutions yielded red cells with 24-hour survivals in excess of 75 percent. Cells stored in AS-3 for 21 days had a mean survival of 77 +/- 8 percent and cells stored in AS 17 a mean survival of 79 +/- 11 percent. The AS-17 solution resulted in improved maintenance of pH, p50, and 2,3 DPG compared to that with AS-3, but both solutions appear adequate for 3 weeks of postthaw storage. PMID- 8212115 TI - Factors affecting Yersinia enterocolitica (serotype O:8) viability in deliberately inoculated blood. AB - Interpretation of in vitro experiments using Yersinia enterocolitica in blood components requires information on factors affecting the organism's survival. Several factors were found to influence the survival of Y. enterocolitica (serotype O:8) in blood components. A 20-minute room-temperature incubation with plasma-containing components resulted in approximately 2 log10 inactivation. Inactivation could be prevented by preincubation treatment of the plasma at 55 degrees C for 1 hour, which suggests the involvement of heat-labile plasma factors. No antibacterial activity was observed in washed red cells during the 20 minute room-temperature incubation. However, Y. enterocolitica colony-forming units declined by up to 2 log10 in washed red cells during the first days of 4 degrees C storage. Use of a white cell-reduction filter on freshly inoculated samples removed approximately 1 log10 of the organism regardless of whether bacteria were suspended in saline or washed red cells. Thus, bacterial levels may be affected by plasma, cellular components, and white cell-reduction filters. However, caution should be exercised in interpreting in vitro spiking studies designed to investigate the potential benefits of white cell reduction to eliminate the growth of Y. enterocolitica because of potential differences between naturally infected and experimentally inoculated blood. PMID- 8212116 TI - The preparation of fibrinogen concentrate for use as fibrin glue by four different methods. AB - Fibrinogen concentrates for use as fibrin glue were prepared by modification of a cryoprecipitate method. The goals were the optimization of a method for different centrifuges and anticoagulants and the assay of factors not previously analyzed. Following a -70 degrees C freeze and a 4 degrees C thaw, CPDA-1 and ACD plasma were centrifuged at 6500 x g for 5 minutes or, alternatively, at 5000 x g for 7 minutes. The supernatant plasma was expressed to a final volume of 15.5 +/- 3 mL, and concentrates were stored at -30 degrees C. Preconcentration and postconcentration samples were analyzed for fibrinogen, fibronectin, factor XIII, and plasminogen content. Fibrinogen in CPDA-1 plasma was significantly higher than that in ACD plasma both before and after concentration at both centrifugation speeds. Fibronectin, factor XIII, and plasminogen concentrations were not significantly affected by centrifugation speed or the type of anticoagulant used. Fibronectin and plasminogen concentrations were significantly increased in components that were held for 5 to 6 days, as compared to those held for 0 to 1 day before freezing. Storage for up to 20 days in CPDA-1 and up to 5 months in ACD did not affect analyte concentration. It is concluded that ACD plasma centrifuged at 5000 x g yields a significantly low concentration of fibrinogen, while CPDA-1 plasma centrifuged at 6500 x g yields the highest amount. Acceptable yields were obtained from centrifugation of ACD plasma at 6500 x g and of CPDA-1 plasma at 5000 x g for use as fibrin glue. PMID- 8212117 TI - Efficacy of preoperative donation of blood for autologous use in radical prostatectomy. AB - To determine the amount of blood lost, the number of transfusions, and the effectiveness of preoperative autologous blood donation in radical prostatectomy, 163 patients' records from 1987 to 1991 were reviewed at four university hospitals and three community hospitals. Calculated red cell volume lost was 1003 +/- 535 mL (mean +/- SD), which corresponds to 44 +/- 18 percent (mean +/- SD) of total red cell volume. Preoperative donation of blood for autologous use reduced the rate of transfusion of allogeneic blood from 66 to 20 percent (p < 0.001). Of the patients who donated 1 to 2 units, 32 percent received allogeneic blood; 14 percent of those who donated 3 units received allogeneic blood. Donation of 4 units reduced the allogeneic transfusion rate to 11 percent. However, as the number of units donated increased (1-3 units), the units not transfused also increased (0-21%). Ninety-one (56%) of 163 patients donated fewer than 3 units. Autologous blood donation is effective in minimizing the transfusion of allogeneic blood to radical prostatectomy patients, but many patients do not donate enough blood (< 3 units). The donation of 3 units of blood for autologous use is recommended for patients who undergo radical prostatectomy. PMID- 8212118 TI - Microwave dissociation of antigen-antibody complexes: a new elution technique to permit phenotyping of antibody-coated red cells. AB - To evaluate the effectiveness of microwave irradiation in dissociating IgG from red cells (RBCs), the use of chloroquine diphosphate (CDP) was compared to that of microwaves. Fifteen paired samples of RBCs from 15 patients with positive direct antiglobulin tests (DATs) were treated with both CDP and microwave radiation. Total microwave exposure times ranged from 20 to 100 seconds. Posttreatment DATs were performed, and the reaction grades of the posttreatment DATs were compared. RBC phenotyping was also performed on repeatedly microwaved RBCs to demonstrate possible effects on RBC antigen expression. Microwaves successfully reduced the reaction grade of the DAT in 14 of 15 samples; CDP reduced the reaction grade in 12 of 15 samples. In samples with a DAT of 2+ or greater (n = 13), the microwave method yielded a greater reduction in DAT strength in six cases (results in the other 7 cases were identical with both methods) (p = 0.01). Five of eight cases with a DAT of 3+ showed a greater reduction in the DAT with microwave treatment than with CDP treatment; results in the remaining three cases were identical (p = 0.03). RBC antigenicity remained unchanged after exposure to microwave radiation (A, B, C, c, D, E, e, Fya, Fyb, Jka, Jkb, K, k, S, and s). Microwave treatment required less than 10 minutes per sample, while CDP treatment required 30 to 120 minutes per sample (mean, 88 min). The microwave technique of antigen-antibody dissociation from RBCs provides a rapid and accurate method of facilitating the phenotyping of RBCs coated with warm autoantibodies and is superior to other methods, which destroy RBC antigens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212119 TI - Filtration through a polyester white cell-reduction filter of plasma-poor platelet concentrates prepared with an acetate-containing additive solution. AB - It is of practical importance to known whether the adsorption of platelets and contaminating white cells (WBCs) by the WBC-reduction filter is altered when platelet concentrates (PCs) are prepared in a plasma-poor condition with an acetate-containing additive solution (Seto sol). Plasma-poor PCs with 11-percent residual plasma were prepared from apheresis platelet-rich plasma by using a sterile docking device with steam-sterilized Seto sol. Seto sol contains 115 mM (115 mmol/L) NaCl, 4 mM (4 mmol/L) KCl, 3 mM (3 mmol/L) MgCl2, 10 mM (10 mmol/L) Na3PO4, 15 mM (15 mmol/L) acetate, 3 mM (3 mmol/L) Na3 citrate, and 10 mM (10 mmol/L) glucose (pH 7.1). The solution was steam-sterilized under nitrogen gas. On Days 1 and 5, pooled Seto sol PCs (2.4 x 10(11) platelets) were filtered with a polyester filter at a flow rate of 10 mL per minute. The WBC-removal rate was over 99.9 percent with a platelet recovery of 88 percent following Day 1 filtration. These values were very similar to those of plasma PCs, and 84-percent recovery was achieved following Day 5 filtration. However, when 1 unit of Seto sol PCs with half the number of platelets was filtered with the polyester filter, platelet recovery was about 16 to 17 percent less than that of plasma PCs. Platelet quality was maintained if pooled Seto sol PCs were filtered on Day 1 and stored for over 4 days. Filtration did not alter platelet function in 1-day-old or 5-day-old Seto sol PCs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212120 TI - Coagulation parameters of CPD fresh-frozen plasma and CPD cryoprecipitate-poor plasma after storage at 4 degrees C for 28 days. AB - A pilot study was performed on the storage of plasma and cryosupernatant plasma at 4 degrees C for up to 28 days. Eight bags, four of CPD fresh-frozen plasma (FFP) and four of CPD cryosupernatant plasma (CSP, plasma without cryoprecipitate), were sampled during storage for assays of pH; factors V, VIII, IX, and XI; fibrinogen; prothrombin time; activated partial thromboplastin time (APTT); plasma protein electrophoresis; viscosity; and C1q binding. No changes were found in viscosity or the plasma protein electrophoretic pattern, and there was no detectable immune complex formation. The fibrinogen concentration remained constant, and the prothrombin time showed a gradual increase of 2.5 seconds for both groups of plasma. The labile coagulation factor V decreased gradually for FFP and CSP to 58 and 64 percent of its initial value, respectively (51 +/- 8% and 54 +/- 6% of the value of fresh pooled plasma). Factor VIII decreased to 36 percent of its initial value in FFP (48 +/- 14% of fresh pooled plasma). In CSP, factor VIII decreased after 28 days to 7 percent of its initial value (7 +/- 1% of fresh pooled plasma). The APTT increased for FFP from 28 to 35.8 +/- 1.1 seconds and for CSP from 36 to 49.5 +/- 4.9 seconds. The only chemical change observed for both plasmas was a rise in pH, from 7.27 to 7.56, after 28 days. The results of this pilot study indicate that FFP can be stored at 4 degrees C for 28 days with sufficient recovery of coagulation factors to maintain hemostasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212121 TI - Frequency of platelet-specific antigens among Indonesians. AB - This study reports the frequencies of the alloantigens of four major platelet specific alloantigen systems among Indonesians. One hundred and sixty-eight unrelated Indonesian blood donors were phenotyped for the alloantigens of the Zw (PIA, HPA-1), Bak (HPA-3), Yuk (Pen, HPA-4), and Br (HPA-5) systems by use of a glycoprotein-specific immunoassay. All were positive for the alloantigens Zwa, Yukb, and Brb. Three (1.79%) and 1 (0.59%) of the 168 donors were positive in testing for Zwb and Yuk(a) antigens, respectively. Fifteen (9.26%) of 162 Indonesians had Br(a) antigens. Of the 166 donors tested, 121 (72.89%) were Bak(a) positive and 134 (80.72%) were Bakb positive. In addition, the phenotype frequency of Nak(a) was determined by using monoclonal antibody OKM5 in a platelet enzyme-linked immunosorbent assay. Its frequency in the present cohort was 95.83 percent (161/168). This study confirms the differences in platelet antigen distributions in Asians and whites. Both glycoprotein IV deficiency and the Yuk polymorphism are also found among Indonesians. PMID- 8212122 TI - Perioperative blood transfusion and colorectal cancer recurrence: a qualitative statistical overview and meta-analysis. PMID- 8212123 TI - Biochemistry, physiology, and function of platelets stored as concentrates. PMID- 8212124 TI - Blood donor-, apheresis-, and transfusion-related activities: results of the 1991 American Association of Blood Banks Institutional Membership Questionnaire. AB - Approximately 2154 regional blood centers and hospital-based blood banks and transfusion services responded to the 1991 American Association of Blood Banks Institutional Membership Questionnaire that elicited data from 1990. Information from 2144 institutions was considered valid. Questionnaire topics were donor blood collections, hemapheresis, perioperative cell salvage, component usage, and transfusion-associated diseases. Institutional members reported collecting 9.3 million units, of which 90.9 percent were for allogeneic use in the community, 6.0 percent were for autologous use, and 3.1 percent were directed donations. The percentage of directed-donor units that were crossed over for allogeneic use (51%) was greater than the percentage of units transfused to the designated patient (49%). Only 12.5 percent of institutions reported obtaining specific consent for transfusion. Of the 15.4 million transfused blood components, 8.5 million were red cells, 4.1 million were platelets, 1.8 million were fresh-frozen plasma, and 0.9 million were cryoprecipitate. There were 1263 reported cases of transfusion-associated hepatitis. Approximately 44 percent of the patients who were tested proved positive for hepatitis B surface antigen, and 80 percent of the patients who were tested proved positive for antibody to hepatitis C. The questionnaire's aggregate results can be used to assess current patterns of blood donation and transfusion activities. PMID- 8212125 TI - Detection of human cytomegalovirus DNA in peripheral blood leukocytes by the polymerase chain reaction. PMID- 8212126 TI - Human monoclonal anti-D with a normal half-life. PMID- 8212127 TI - Fatal transfusion-associated graft-versus-host disease caused by blood from an unrelated donor in an immunocompetent patient. PMID- 8212128 TI - How some retroviruses got their oncogenes. PMID- 8212129 TI - Novel predictions from radiation target analysis. AB - The unusual technique of radiation inactivation has been used to determine the mass of many different macromolecules. Most of the radiation target sizes obtained agree with the known protein structures. However, in several cases the sizes obtained were not easily interpreted since they did not agree with values determined by more conventional methods. Subsequent studies have shown that many of these perplexing radiation target sizes were indeed correct, often revealing unanticipated details about the nature of the systems being studied. PMID- 8212130 TI - Lateral communication by fast proton conduction: a model membrane study. AB - Lateral communication of information along biological membranes is thought to be a key process for many cellular activities. Support for this hypothesis comes from physicochemical experiments that show that an efficient facilitated lateral proton conduction exists along lipid-water interfaces. The existence of a local two-dimensional hydrogen bond network between the lipid headgroups and their associated water molecules would explain this phenomenon. PMID- 8212131 TI - Exopolyphosphate phosphatase and guanosine pentaphosphate phosphatase belong to the sugar kinase/actin/hsp 70 superfamily. PMID- 8212132 TI - Vesicular transporters join the major facilitator superfamily (MFS) PMID- 8212133 TI - Uniform nomenclature for the mitochondrial peptidases cleaving precursors of mitochondrial proteins. PMID- 8212134 TI - The effector interactions of p21ras. AB - Genetic, physical and biochemical methods have been used successfully to identify discrete regions of the p21ras protein involved in protein-protein interactions. Of special interest are the effector residues of p21ras, which are essential for downstream signalling. This review details current understanding of what these residues are and how they bind and activate proteins essential to the ras pathway. PMID- 8212135 TI - RNA recognition by the human immunodeficiency virus Tat and Rev proteins. AB - The human immunodeficiency virus (HIV-1) regulatory proteins, Tat and Rev, are important potential targets for the development of new drug therapies against HIV infection. Both proteins are highly specific RNA-binding proteins that recognize cis-acting regulatory elements in the viral mRNAs. These interactions are fascinating paradigms of a new principle of RNA recognition in which the protein makes contact with functional groups displayed in a distorted major groove of an RNA duplex. PMID- 8212136 TI - The leucine-responsive regulatory protein: more than a regulator? AB - The leucine-responsive regulatory protein (Lrp) is the regulator of the recently discovered leucine/Lrp regulon in Escherichia coli. Like other global regulators, it regulates the expression of 35 or more specific target operons. Studies of this global response have led to the suggestion that Lrp--and perhaps some other gene regulators--may also participate in the maintenance of chromosome structure and organization. PMID- 8212137 TI - Sequence analysis by electronic mail server. PMID- 8212138 TI - The greater vulnerability of bile duct cells to reoxygenation injury than to anoxia. Implications for the pathogenesis of biliary strictures after liver transplantation. AB - The occurrence of biliary strictures in allografts following liver transplantation correlates with the duration of preservation time. The correlation between preservation time and biliary strictures suggests that anoxic or reperfusion injury of the bile duct epithelium causes stricture formation. However, the relative susceptibility of bile duct cells to anoxic or reoxygenation injury is unknown. Our aims were to determine the vulnerability of rat liver bile duct cells to anoxic and reoxygenation injury and to compare the results with hepatocytes. During anoxia, bile duct epithelial cells were significantly more resistant to cell killing than hepatocytes. Rates of cellular proteolysis were also 2.5-fold lower in bile duct cells than in hepatocytes during anoxia. In contrast to anoxia, reoxygenation of anoxic cells increased cell killing of bile duct cells but improved viability of hepatocytes. The rate of toxic oxygen species formation by bile duct cells was 5-fold greater than in hepatocytes during reoxygenation. In addition, basal levels of glutathione are lower in bile duct cells than in hepatocytes. These data suggest that bile duct cells are more susceptible to reoxygenation injury than to anoxia. These studies support the hypothesis that reoxygenation injury during liver preservation leads to bile duct injury during liver transplantation. PMID- 8212139 TI - Rat pancreas preparation for cold storage and subsequent islet cell isolation. AB - Pancreatic islets can be isolated from cold-preserved organs. They contain 60% more beta cells when prepared from organs that were stored for 24 hr in Collins solution supplemented with albumin and benzamidine (CAB) instead of University of Wisconsin (UW) solution. Recovery from CAB-stored organs was similar when CAB was perfused in situ before organ removal or ex vivo after organ harvesting in UW. In situ flush with cold Ringers before ex vivo replacement by CAB resulted in 25% lower recovery of islet beta cells and in higher contamination with nonendocrine and damaged cells. Recovery of beta cells was 50% reduced when cold storage solution was not chased before collagenase digestion of the organ. It is concluded that the isolation of rat islets from cold-preserved organs can be improved by using UW or CAB instead of Ringers for situ perfusion, by cold storage in CAB, and by adequate chase of cold storage solution with physiologic medium before collagenase digestion. These conditions can be tested in current human islet isolation protocols. PMID- 8212140 TI - Accelerated rejection of H-2-incompatible skin allografts in the absence of specific cytotoxic antibodies. AB - Second-set rejection is generally considered to be mediated by cytotoxic humoral antibodies. A few discordant data have been reported, however. To address this question, we have taken advantage of a model in which specific cytotoxic alloantibodies are not produced although transplantation cellular immunity develops. Following a transplant of allogeneic stem cells from fetal liver, chimeric mice (BALB/c-->CBA--i.e., H-2d-->H-2k) were obtained; virtually all peripheral blood lymphocytes and spleen cells were of BALB/c donor origin. Anti sheep red blood cell humoral response was present, although significantly lower in chimeras than in controls. These allochimeras were hyperimmunized by skin grafts and injections of spleen cells. The survival of skin grafts and the production of antibodies were then analyzed. When hyperimmunized against a third party, B6 (H-2b), chimeric mice were not able to raise a detectable humoral response involving anti-B6 cytotoxic antibodies, yet they rejected B6 skin allografts in an accelerated fashion (8.44 +/- 0.17 days). Control CBA mice rejecting second-set B6 skin grafts within the same delay developed high-titer, specific cytotoxic antisera (mean titer = 140). These data show that cytotoxic allospecific antibodies are not indispensable in the development of second-set accelerated rejection of skin allografts. PMID- 8212141 TI - A new technique for early detection of portal vein and arterial thromboses. Indwelling mesenteric venous catheterization and relevance to small bowel transplantation. AB - The aim of this study was to ascertain whether, in an animal model, continuous monitoring of mesenteric venous pressure (MVP) via an indwelling mesenteric venous catheter could assist in early detection of thrombosis of the portal vein (PVT) and superior mesenteric artery (SMAT). The role of portography via the catheter was also studied in confirming these complications. An animal model of PVT and SMAT was developed in pigs. At laparotomy, a 20-cm jejunal loop was isolated and a heparin-coated catheter was inserted into a mesenteric vein of the isolated jejunum and connected to a pressure transducer. Conditions of PVT were simulated by progressive occlusion of the portal vein (PV) using a silastic tourniquet and those of SMAT by superior mesenteric artery (SMA) clamping. MVPs (mm Hg) were found to significantly increase with all degrees of PV occlusion (P < 0.01, Student's t test) and to significantly decrease after SMA occlusion (P < 0.01). Portography clearly demonstrated all degrees of PV stenosis after PV occlusion and stasis of contrast medium during SMA occlusion. The authors feel that this method enables rapid diagnosis of PVT and SMAT and may be useful in the monitoring of the therapy for these complications after small bowel transplantation. PMID- 8212142 TI - Improvement of structure and function in orthotopic small bowel transplantation in the rat by glutamine. AB - Significant atrophy and impaired absorption occur in the heterotopically transplanted small intestinal isograft, and these deficits are corrected when the preferred fuel of the enterocyte, glutamine (Gln), is supplemented to total parenteral nutrition (TPN). In the orthotopic small bowel isograft, this study determined whether Gln-enriched TPN enhanced mucosal structure and function, and decreased bacterial translocation to mesenteric lymph nodes (MLN). Seventeen adult Lewis rats received orthotopic jejunal isografts and central venous catheters for TPN. Rats received either TPN with 2% Gln or the same TPN with isonitrogenous balanced nonessential amino acids for 10 days. Eight normal, chow fed rats served as baseline controls. Mucosal villous height, surface area, crypt depth, weight, protein and DNA contents, brush border enzymes, 14C glucose absorption, and bacterial translocation to MLN were evaluated in both the graft and host jejunum and the control animals. Gln-enriched TPN significantly increased mucosal villous height (P < 0.01), surface area (P < 0.01), and glucose absorption (P < 0.01), and it reduced bacterial translocation (P < 0.05) when compared with the non-Gln TPN group. For most study variables, there were no significant differences between Gln-enriched TPN or baseline and between the graft and host jejunum for Gln- and non-Gln-supplemented animals. There were no significant differences in DNA content and brush border enzymes among groups. These results indicate that Gln-enriched TPN improves mucosal structure and glucose absorption and reduces bacterial translocation to MLN in the orthotopic small bowel isograft. PMID- 8212143 TI - The immunosuppressive effect of 5-lipoxygenase inhibitor on liver allotransplantation in rats. AB - This study was performed to examine the immunosuppressive effect of a 5 lipoxygenase inhibitor, AA-861, on liver transplantation in rodents, and also to examine the production of eicosanoids during rejection of liver allograft in these animals. Rats were divided into three groups: group I (syngenic orthotopic liver transplantation from LEW to LEW), group II (allogenic OLT from ACI to LEW with dimethyl sulfoxide), and group III (allogenic OLT from ACI to LEW with AA 861 [20 mg/kg/day] s.c. dissolved in DMSO). Histological examinations were performed, survival time was monitored, and eicosanoid levels at 3, 5, and 7 days after transplantation were measured. Mean survival time in group III was significantly longer than that in group II (36.0 +/- 6.8 vs. 11.1 +/- 0.7 days, mean +/- SEM; P < 0.01). Histologically, the degree of rejection in group III was moderate compared with that in group II. On day 3, the LTB4 level in group II was significantly higher than that in group I (3361 +/- 985 vs. 407 +/- 70 pg/ml, P < 0.05), and the PGE2 level in group III was significantly higher than that in group 1 (50.3 +/- 4.8 vs. 23.5 +/- 4.7 pg/ml, P < 0.01) and in group II (32.9 +/- 4.2 pg/ml, P < 0.05). These findings suggest that AA-861 reduced liver allograft rejection by suppressing the elevation of 5-lipoxygenase products and increasing PGE2 production in the early stage of rejection. PMID- 8212144 TI - Survival and function of purified islets in the omental pouch site of outbred dogs. AB - The aims of this study were to devise an omental pouch site for islet implantation in a preclinical large animal and to compare the function of islets engrafted to this site with islets implanted into the spleen. Highly purified islets were isolated from outbred mongrel dogs, then grafted into totally pancreatectomized outbred recipients. Autografts of islets were implanted into a greater omental pouch (group [gp] 1, n = 12) or into the spleen by venous reflux (gp 2, n = 12). Allografts of single donor islets were implanted into the omental pouch (gp 3) of dogs that received CsA (n = 9) or untreated controls (n = 3). The threshold islet mass that consistently reversed diabetes in gp 1 was 10 microliters/kg, which exceeded by 2.5-fold that required in gp 2. Normoglycemia was induced and maintained for 2 months in 6 gp 1 and 8 gp 2 dogs. At IVGTT, the K value (decline in glucose, %/min) was 1.3 +/- 0.4 in gp 1 versus 1.5 +/- 0.2 in gp 2 (P > 0.2). Peripheral venous insulin levels were significantly lower (P < 0.01) in gp 1. Omentectomy (gp 1) or splenectomy (gp 2) induced prompt hyperglycemia. All gp 3 dogs (received > 10 microliters/kg) were initially normoglycemic: grafts of untreated controls failed at 4.2 +/- 1.8 days. In 1 CsA treated dog the graft failed for technical reasons; normoglycemia persisted in the other 8 for 10, 15, and 21 days, and in 5 instances for > 30 days. When CsA therapy was stopped at 30 days, normoglycemia persisted for 34 +/- 9.5 days. We conclude that purified islets restore normoglycemia after implantation into the omental pouch of diabetic dogs. Compared with intrasplenic islet implantation, an increased graft volume is required and insulin levels are lower. PMID- 8212145 TI - Diminution of an acute cyclosporin-induced cholestasis by tauroursodeoxycholate in the rat. AB - CsA is a commonly used immunosuppressive drug known to possibly induce cholestatic side effects. Ursodeoxycholic acid (UDC), a nonhepatotoxic bile acid, has proved to be efficient for several types of cholestasis. The aim of this experiment was to evaluate the ability of tauroursodeoxycholate (TUDC) in preventing CsA-induced cholestasis on bile duct-cannulated rats. After bile flow stabilization, a bolus of 30 mg/kg CsA was given i.v. to one group (n = 7) and was associated with a 2 mumol/kg/min TUDC infusion in another group (n = 7). The control group was injected with CsA-solvent. CsA, as used here, had a rapid and marked cholestatic effect. However, both bile flow and bile salt secretion were significantly enhanced in the TUDC group when compared to the CsA alone-treated group and showed no difference with the solvent control group. In addition, TUDC significantly increased elimination of CsA and its metabolites in bile. In contrast to what was found for endogenous bile salts, TUDC uptake was not affected by CsA. The anticholestatic effect of TUDC probably resulted from preventing CsA-induced hepatocyte membrane damage and from easing biliary excretion of CsA. Such properties could be helpful for CsA-treated liver recipients who are especially exposed to cholestatic problems, and thus, to toxic CsA accumulation in the liver. Moreover, regulation of CsA elimination might prevent, in part, its general toxicity. PMID- 8212146 TI - Late cyclosporine treatment ameliorates established coronary graft disease in rat allografts. AB - The development of post-transplantation coronary graft disease (CGD) is a major cause of late morbidity and mortality. Recent reports have suggested that CGD is a type of chronic vascular rejection, possibly enhanced by cofactors such as concurrent CMV infection and hyperlipidemia. It remains controversial whether established CGD can be improved by modifications in immunosuppressive therapy. The purpose of this study was to examine whether CsA could reverse or halt the progression of CGD after it was already established. Lewis to Fisher (F-344) heterotopic heart allografts develop CGD resembling human disease. Group 1 (n = 29) had no CsA therapy for chronic rat CMV (RCMV) infection in recipients for 8 weeks before transplant. Group 2 (n = 17) had chronic RCMV infection along with CsA therapy from days 15 to 28 post-transplant. Allografts were killed at 2 and 4 weeks and 90 days post-transplantation. In group 1, leukocyte adhesion to arterial endothelium and intimal hyperplasia were well established at 2 weeks and progressed to stenotic, proliferative arterial lesions at 4 weeks. In group 2, CsA therapy was effective in significantly reversing histologic parameters of vascular rejection such as leukocyte adhesion, intimal proliferation, and periarterial edema at 4 weeks. By 90 days, however, arterial pathology was as severe as in group 1. In conclusion, these results support the hypothesis that CGD is a form of chronic vascular rejection, and once established, can be significantly modified by CsA therapy. These effects are not permanent, and progressive CGD recurs after CsA therapy is discontinued. PMID- 8212147 TI - Bone marrow transplantation in miniature swine: IV. Development of myeloablative regimens that allow engraftment across major histocompatibility barriers. AB - Studies of the myeloablative regimens capable of permitting successful BMT across MHC barriers in miniature swine have been performed. To minimize graft-versus host disease (GVHD), engraftment was studied in the F1-->P combination (i.e., MHC homozygous ["parental"] swine receiving bone marrow from one-haplotype matched MHC heterozygous ["F1"] donors). Animals given total body irradiation (TBI) up to 1100 cGy, 10 cGy/min, in a single dose failed to engraft. Increasing the dose rate led to unacceptable extramedullary toxicity without improving engraftment. Eleven different fractionated TBI regimens were tested in this F1-->parent model. At all of the dose rates tested, a total dose of less than 1000 cGy was insufficient for engraftment, and a total dose of 1400 cGy led to unacceptable toxicity. Between these extremes, a window was defined in which engraftment could be obtained without unacceptable extramedullary toxicity utilizing 2 equally divided fractions of TBI delivered 24 hr apart. The addition of 50 mg/kg cyclophosphamide i.v. to fractionated TBI (1150 cGy total dose [500 + 650]) also permitted engraftment, with decreased incidence of interstitial pneumonitis as compared to fractionated TBI (1300 cGy total dose [650 x 2]). Both of these regimens were also confirmed to permit engraftment between heterozygous donors and recipients sharing a single common haplotype ("F1-->F1"). The regimen of 1300 cGy (650 x 2) also permitted engraftment in completely MHC mismatched BMT, but with subsequent death from GVHD. These studies of the myeloablative regimens permitting engraftment across defined MHC barriers in miniature swine provide a basis for further studies of allogenic BMT and GVHD in this large animal preclinical model. PMID- 8212148 TI - Human islet isolation--a prospective randomized comparison of pancreatic vascular perfusion with hyperosmolar citrate or University of Wisconsin solution. AB - University of Wisconsin solution has become the most commonly used vascular perfusate during multiorgan donation world-wide. In the UK however, hyperosmolar citrate remains in common use. The purpose of this prospective randomized study was to compare the effect of systemic perfusion with UW or HOC on subsequent islet yield and purification for pancreata with short cold ischemic times. Seven pancreata were randomized to each group, with the donor age, pancreas weight, and period of cold ischemia being similar in both. Perfusion with UW was shown to inhibit collagenase digestion, and a higher concentration of this enzyme was needed to achieve comparable numbers of islets with good separation of exocrine and islet tissue after a similar period of digestion. There were no differences in the number, size, purity, or viability of islets between the two groups. In conclusion, UW solution offers no benefits over HOC for pancreata with short cold ischemic times, and because of its expense and need to use greater amounts of collagenase enzyme, we continue to use HOC. PMID- 8212149 TI - An analysis of liver transplant experience from 37 transplant centers as reported to Medicare. AB - Analysis of 5180 liver transplant cases from 37 liver transplant centers in the United States (1982-1991) shows an overall one-year survival rate of 79.4 +/- 0.6% and a five-year survival rate of 69.2 +/- 0.9%. There was marked improvement in the one-year survival rate after liver transplantation from 36.0 +/- 9.6% in 1982 to 85.0 +/- 1.8% in 1991. One-year survival rates after liver transplantation for postnecrotic cirrhosis, primary biliary cirrhosis, alcoholic cirrhosis, primary sclerosing cholangitis, alpha-1-antitrypsin deficiency, and Wilson's disease ranged from 78.4 +/- 1.0% to 84.2 +/- 1.5% and five-year survival rates from 68.6 +/- 3.8% to 79.2 +/- 5.3%. Survival rates after liver transplantation for hemochromatosis were poor--a one-year survival rate of 53.8 +/- 6.8% and a five year survival rate of 43.1 +/- 11%. One- and five-year survival rates for the 0-13 years age group were 74.6 +/- 2.8% and 66.7 +/- 3.4%; for the 14-37 years age group, 83.3 +/- 1.2% and 73.8 +/- 1.8%; for the 38-54 years age group, 79.6 +/- 0.8% and 69.7 +/- 1.3%; for the 55-63 years age group, 76.0 +/- 1.4% and 63.0 +/- 3.1%; and for the 64-77 years age group, 76.5 +/- 3.0% and 65.4 +/- 4.6%. PMID- 8212150 TI - Quality of life of liver transplant recipients. A pilot study. AB - In a cross-sectional survey of the quality of life of 45 liver transplant recipients, physical and psychological status, physical complaints, capability to participate in daily life, social support, and global quality of life were assessed. The average time of follow-up was 9 months after transplantation. Nine patients had moderate liver damage, 12 suffered from drug side effects, and 10 had extrahepatic diseases. Physical complaints, especially rheumatism, exhaustion, and gastric complaints, were higher than in the general population. Most patients were able to participate in daily life (do housework, take part in family life, etc.). Apart from the complex "health" (use of body), they did not differ in this respect from healthy individuals. Eighty percent of the patients reported having very good social support. The psychological status was generally good, with only 5% complaining of anxiety and nervousness. Sixty percent regarded their quality of life to be very high, 31% reported medium quality of life, and 9% felt very bad. No relationship was found between low quality of life and transplant malfunction; patients with extrahepatic diseases had the lowest quality of life. Among all subgroups, the individuals who were actively working again felt best. Psychological qualities necessary for coping with daily life (self-assurance, self-realization, satisfaction, and happiness) correlated most with the global quality of life (r = 0.80), whereas no relationship was found between quality of life and complaints in total (r = -0.32). This survey shows that during the first year after transplantation, transplant recipients report a high quality of life in important areas of living, despite many physical complaints, and even display an almost euphoric mood. PMID- 8212151 TI - Relationship of the polymerase chain reaction for cytomegalovirus to the development of hepatitis in liver transplant recipients. AB - In a pilot study, the polymerase chain reaction was found to be more sensitive than standard viral culture methods for the detection of cytomegalovirus, particularly from blood and tissues. We therefore applied this technique to 71 serially collected liver biopsies from 16 orthotopic liver transplant patients. All patients were CMV-seropositive (n = 15) or seroconverted (n = 1). Seven patients (9 biopsies) had histologically proved CMV hepatitis, and all these biopsies were CMV PCR-positive. Six of these 7 patients had a prior liver biopsy that was CMV PCR-positive, but culture and histology-negative, an average of 13.2 +/- 6.9 days before the histologically positive biopsy. The 7th patient was not biopsied prior to the diagnostic biopsy. Three patients had 7 liver biopsies that were CMV PCR-positive, but histologically negative for CMV hepatitis. Two of these three had CMV infection confirmed by viral culture of blood or liver biopsy. The remaining 6 patients had a total of 26 liver biopsies that were negative for CMV by PCR, culture, and histology. Among liver transplant patients, CMV PCR performed on liver biopsy specimens correctly identified all histologically proven cases of CMV hepatitis. CMV PCR positivity in liver tissue did not correlate with latent infection and preceded the development of CMV hepatitis or other meaningful CMV infection in 8 of 10 patients. PMID- 8212152 TI - Prednisone therapy for acute graft-versus-host disease: short- versus long-term treatment. A prospective randomized trial. AB - We report the results of a controlled study in which BMT patients with moderate/severe acute graft-versus-host disease (GVHD) who responded to primary treatment with corticosteroids were prospectively randomized to short versus long taper of their steroid doses. Thirty patients with moderate/severe acute GVHD who responded by 14 days were eligible for random assignment of their steroid tapering schedule. Patients in the short taper group received a total PRED dose of 2275 mg/m2 over 86 days, whereas those in the long taper group received 6300 mg/m2 over 147 days. Patients in the long taper group achieved resolution of acute GVHD after a median of 30 days of therapy (range 6-30), whereas those receiving the short taper resolved after a median of 42 days (12-74) (P = 0.01). After 8 weeks of therapy, only 2 of 13 evaluable long taper and 3 of 13 short taper patients still had active GVHD. The median PRED dose required to achieve complete resolution of acute GVHD was not different between the two groups: 1300 mg/m2 for the long taper patients and 1800 mg/m2 for the short taper patients. Importantly, the incidence of chronic GVHD and survival at 6 months was similar in the 2 groups. The incidence of steroid-related complications was similar, as well. This study suggests that the rapid administration of high-dose PRED to a cumulative dose of 2000 mg/m2 might lead to complete and prompt resolution of acute GVHD in the majority of patients and that rapid PRED taper might provide a mechanism for minimizing steroid-related morbidity. Further investigation and formal studies of the dose-response relationships and kinetics of steroid administration may lead to improvement in the management of acute GVHD. PMID- 8212153 TI - Segmental localization and quantitative characteristics of tubulitis in kidney biopsies from patients undergoing acute rejection. AB - The term tubulitis denotes infiltration of the renal tubular epithelium by mononuclear cells. Tubulitis is one of the most reliable signs of acute renal allograft rejection. However, its segmental localization and quantitative characteristics are not precisely known. To investigate this question, formalin fixed kidney biopsy specimens from 15 patients with transplanted allografts undergoing acute rejection were studied stereologically by identifying cortical tubules with segment-specific markers. The periodic acid-Schiff reaction, peanut lectin, and antibodies against Tamm-Horsfall protein and epidermal cytokeratins, all applied to the same section, were used to identify the profiles of proximal tubules (PTs), distal convoluted tubules (DCTs), distal straight tubules (DSTs), and the cortical collecting system (CCS, connecting tubules and cortical collecting ducts), respectively. Two parameters, the relative intrasegmental length and the average intensity of tubular damage, were determined to describe the degree of tubulitis quantitatively. Tubulitis was most prominent in the DCTs, followed by the CCS. The average intensity of tubulitis was lowest in the DSTs. The results indicate that the PTs are not the main site of tubulitis, despite the fact that they are regarded primary targets of the rejection response. PMID- 8212154 TI - Anemia in renal transplant recipients caused by concomitant therapy with azathioprine and angiotensin-converting enzyme inhibitors. AB - Immunosuppression of recipients of renal transplants with azathioprine has been associated with two major side effects: hepatotoxicity and myelotoxicity, mainly in the form of leukopenia. Reports of isolated anemia in these patients have been rare. We now observed the development of severe anemia in 9 out of 11 renal transplant recipients whose immunosuppressive regimen was converted from cyclosporine plus prednisone to azathioprine plus prednisone. A significant (P = 0.001) drop in hematocrit (from 34 +/- 4% to 27 +/- 3%, mean +/- SD) and hemoglobin (from 11.6 +/- 1.3 g/dl to 9.5 +/- 1.0 g/dl) was found. Since a common variable of all these patients was their use of an angiotensin-converting enzyme (ACE) inhibitor as antihypertensive medication, we speculated that the combination of azathioprine and ACE blocker might be the reason for the anemia. We then compared 2 groups of 10 patients each who had been on azathioprine as their regular immunosuppressive agent and who did or did not take an ACE inhibitor. Hematocrit and hemoglobin were significantly (P = 0.01) lower in the group of patients taking ACE inhibitors (33 +/- 6% versus 41 +/- 5% and 11.5 +/- 2.0 g/dl versus 14.0 +/- 1.6 g/dl, respectively). Haptoglobin levels were also significantly (P = 0.05) lower in the ACE inhibitor group (116 +/- 65 mg/dl versus 210 +/- 114 mg/dl). Erythropoietin concentration in the serum and the reticulocyte index were slightly, but not significantly, higher in the ACE inhibitor group but the values were probably too low for their degree of anemia. Comparing hematological parameters of the patients in the ACE inhibitor group before and after beginning of the antihypertensive treatment confirmed a significant reduction of hematocrit and hemoglobin following therapy with an ACE inhibitor. Hematocrit fell from 41 +/- 7% to 36 +/- 6% and hemoglobin from 14.0 +/- 2.3 g/dl to 11.3 +/- 1.5 g/dl (P < 0.05 for both). We conclude that the combination of these two drugs should probably be avoided. PMID- 8212155 TI - Comparison of adrenal functions in kidney transplant recipients with different long-term immunosuppressive treatments--prednisolone and azathioprine versus prednisolone and cyclosporine. AB - Adverse effects of cyclosporine on the adrenal cortex have been documented in animal experiments, but nothing has been reported in human subjects. Endogenous cortisol in peripheral blood was monitored for three years after transplantation, with 30 kidney recipients on two different immunosuppressive treatments. In the azathioprine group, 16 patients were treated with coadministration of prednisolone at an initial dose of 120 mg/day. In the cyclosporine group, 14 patients were also treated with prednisolone, using an initial dose of 60 mg per day. Short ACTH stimulation tests were performed to reconfirm the results obtained by basal cortisol monitoring. During the first year following transplant, cortisol concentrations in the cyclosporine group were higher, though not significantly so, than those in the azathioprine group, in accordance with cumulative amounts of prednisolone administered. At three years, however, the mean cortisol concentrations in the azathioprine group were 2-3 times higher than those in the cyclosporine group (P < 0.05). All patients in the azathioprine group responded well to ACTH, whereas 4 patients out of 14 in the cyclosporine group showed continuous severe suppression without considerable response to ACTH (P < 0.01). In conclusion, we would like to suggest that adrenocortical toxicity of long-term cyclosporine use may appear one year after transplant, resulting in chronic suppression of the adrenal cortex, and, accordingly, difficulty in further reduction of prednisolone use. PMID- 8212156 TI - Risk factors for postimplantation pancreatitis and pancreatic thrombosis in pancreas transplant recipients. AB - Reperfusion pancreatitis and pancreatic thrombosis are 2 complications of pancreatic transplantation that are associated with both an increased patient morbidity and a decrease in pancreas graft survival rates. These complications are thought to be related to donor factors, procurement and preservation variables, and postimplantation recipient management. We reviewed our experience with 41 consecutive pancreas transplant patients (18 females, 23 males) performed in association with kidney transplants (n = 34), whole (n = 5) and segmental (n = 2). The average cold ischemia time (CIT) was 11.5 hr. Donor and recipient variables were related to two outcomes: (1) postoperative pancreatitis (n = 9) and (2) postoperative pancreatic thrombosis (n = 6). Steroid administration to the donor resulted in significant reduction of postimplantation pancreatitis (P < 0.001). Also, postoperative pancreatitis was significantly less common (P < 0.02) in recipients given calcium channel blockers in the early postoperative period. Pancreatic thrombosis was significantly more common in male recipients (P < 0.04) and was also significantly related to CIT (P < 0.05). These data indicate that proper donor management and pretreatment with high-dose steroids, together with shortening of CIT and postoperative administration of calcium channel blockers, are protective against pancreatic thrombosis and pancreatitis. PMID- 8212157 TI - In situ preservation of kidneys from non-heart-beating donors--a proposal for a standardized protocol. AB - The growing success in renal transplantation has resulted in an increase in the need for donor organs. Procurement of kidneys from heart-beating (HB) donors is unlikely ever to meet this demand. Non-heart-beating (NHB) donors offer a yet untapped source of renal grafts. Cadaver kidneys from patients who have sustained cardiac standstill are often considered unsuitable for transplantation due to prolonged warm ischemia time. Using an emergency in situ perfusion technique it is possible to limit warm ischemic damage and to salvage these kidneys for transplantation. The procedure requires prompt action and cooperation of emergency service personnel. This report presents a protocol for the emergency in situ preservation procedure that can be practiced in most hospitals. At the University Hospital of Maastricht, The Netherlands, implementation of this procedure resulted in 20% more kidneys available for transplantation. Although NHB donor kidneys showed a higher rate of delayed function compared with a matched HB donor kidney population, there was no significant difference in long term graft survival between the two groups. PMID- 8212158 TI - Encrusted pyelitis and cystitis by Corynebacterium urealyticum (CDC group D2): a new and threatening complication following renal transplant. AB - We evaluated the pathogenic role of Corynebacterium urealyticum in the development of encrusted pyelitis (EP) and encrusted cystitis (EC), and their clinical consequences in renal transplant recipients. During a 4-year period, we studied seven renal transplant recipients with EP and two with EC. The records of 320 other renal transplant patients studied during the same period were used as a control group. C urealyticum (> or = 10(5) CFU/ml) was isolated from 4 patients with EP (urine 3, blood 1) and from 1 patient with EC (urine). Alkaline urines with struvite crystals, microscopic hematuria, and sterile conventional urine cultures were present in all our cases. All the patients with EP developed obstructive uropathy with deterioration of the renal function and pyelonephritis (4 patients) or renal abscesses (3 patients). Chronic urinary discomfort and macroscopic hematuria were present in the 2 patients with EC. Long-term vesical and ureteral catheterization were considered the most important risk factors for the development of EC and EP, respectively. Vancomycin was successfully used in 5 cases, but all the patients required a derivative procedure or a surgical resection of the incrustations to improve. We conclude that EP and EC should be investigated in renal transplant patients who develop pyelonephritis, obstructive uropathy, or chronic urinary symptoms. EP and EC could lead to the loss of their grafts. C urealyticum appears to have a pathogenic role in these entities. PMID- 8212159 TI - In situ production of interleukin-6 within human lung allografts displaying rejection or cytomegalovirus pneumonia. AB - Interleukin-6 (IL-6) is a pleiotropic cytokine that is a regulator of inflammation and immunity. As production of IL-6 may be an important mechanism by which local and systemic inflammatory processes are regulated during lung transplantation, we measured this cytokine concentration in the serum and bronchoalveolar lavage fluid (BALF) collected in 27 lung recipients. IL-6 bioactivity was analyzed using a B cell hybridoma proliferation assay (B9 cell line). Three groups of clinical situations were analyzed: control lung recipients, rejections, and CMV pneumonia. Serum IL-6 concentrations (mean +/- SEM) were 24.2 +/- 3.3 U/ml in the 26 control samples. In 20 allograft rejection episodes, the serum IL-6 concentration was higher than in control samples but the difference was not significant (59.3 +/- 20.5 U/ml, P > 0.05). IL-6 serum levels were significantly increased during the 14 CMV pneumonias (61.2 +/- 11.5 U/ml, P < 0.01). In BALF, IL-6 levels were increased during CMV pneumonia (52.4 +/- 21.9 U/ml BALF), and to a lesser extent during rejection events (14.1 +/- 3.7 U/ml BALF), as compared with controls (5.6 +/- 1.6 U/ml BALF, P < 0.005, and P < 0.05, respectively). Similar results were observed when IL-6/albumin and IL-6/urea ratios were determined so as to compensate for possible dilution effects in BALF. IL-6 in BALF was produced in situ during CMV pneumonia as shown by in situ hybridization experiments that revealed a significant number of IL-6 gene expressing alveolar cells in this condition. IL-6 concentrations in the serum and in the BALF were compared. There was no correlation between serum and BALF IL-6 concentrations, showing that serum IL-6 levels do not accurately reflect intrapulmonary IL-6 levels do not accurately reflect intrapulmonary IL-6 production. Thus IL-6 is produced within lung transplants during CMV pneumonia, and to a lesser extent during allograft rejection. PMID- 8212160 TI - Evidence that functional deletion of donor-reactive T lymphocytes in kidney allograft recipients can occur at the level of cytotoxic T cells, IL-2-producing T cells, or both. A limiting dilution study. AB - The frequencies of circulating donor-reactive cytotoxic lymphocyte precursors (CLP) and Il-2-producing helper lymphocyte precursors (HLP) were determined by limiting dilution analysis in 19 kidney allograft recipients before and at various intervals (up to 2 years) after transplantation. A significant, selective, and stable reduction of the frequencies of donor-reactive (but not of third party-reactive) CLP and/or HLP was observed in some patients beginning 3 to 6 months after transplantation. One patient developed reduced frequency of CLP only, 3 patients reduced frequencies of HLP only, and 2 patients reduced frequencies of both CLP and HLP. The selective reduction of donor-reactive CLP and/or HLP frequencies ranged from 5-25-fold when compared with the pretransplantation level and was associated with stable graft function. These data indicate that functional deletion of circulating donor-reactive T cells can occur at the level of cytotoxic T lymphocytes, Il-2-producing helper T lymphocytes, or both. Implications of these findings for the individualization of immunosuppressive regimens will be discussed. PMID- 8212161 TI - Evidence that clonal anergy is induced in thymic migrant cells after anti-CD4 mediated transplantation tolerance. AB - Diabetic (B6) (IE-) mice treated with a depleting regimen of anti-CD4 monoclonal antibody at the time of transplantation with A/J (IEK) islets of Langerhans showed indefinite acceptance of their islet allograft, as evidenced by persistent normoglycemia. To address the mechanisms involved in such anti-CD4 induced transplantation tolerance we studied potentially IE-reactive V beta 11+ T cells from the tolerant allografted mice. Following complete repopulation of the CD4+ cells, both the CD4+V beta 11+ and CD8+V beta 11+ T cell subsets of the transplanted mice were unresponsive to anti-V beta 11 specific crosslinking. In contrast, lymphocytes tested within the first ten days following transplant were responsive to anti-V beta 11 specific crosslinking; this response decreased as a function of time and reached background levels by day 120 posttransplant. Sorting experiments indicated that the response of lymphocytes to anti-V beta 11 specific crosslinking seen during the initial 120 days posttransplant was confined to the peripheral CD8+ cells; the repopulating CD4+V beta 11+ T cells were unresponsive. In addition, administration of r-IL-2 at the time of transplantation induced rejection in anti-CD4-treated animals, again indicating that the peripheral CD8+ cells could respond shortly after transplant if provided with appropriate help. The decreasing response of CD8+ T cells from transplanted animals to anti-V beta 11 stimulation was inversely correlated with the rate of migration of cells from the thymus to the periphery, implying that new thymic migrant V beta 11+ cells, both CD4+ and CD8+, were rendered anergic upon encountering peripheral alloantigen. These data suggest the possibility that recent thymic migrants are rendered anergic upon encountering antigen in the periphery, a simple model to serve as a "fail-safe" mechanism to prevent autoreactivity. PMID- 8212162 TI - Prevention of overt diabetes and insulitis by intrathymic injection of syngeneic islets in newborn nonobese diabetic (NOD) mice. AB - Based on previous studies showing that allogeneic islets transplanted into the thymus can induce donor-specific unresponsiveness, we investigated in the nonobese diabetic (NOD) mouse the effect of intrathymic islet isografts on preventing autoimmunity directed against pancreatic islet antigens. Islets prepared from newborn NOD pancreata were injected into one lobe of the thymus of 10- to 11-day-old female NOD mice (experimental group) with no immunosuppression. PBS alone was used for injection into age- and sex-matched litter mates (control group). Thirty of 32 (94%) experimental mice remained normoglycemic for over 30 weeks. Well-formed islets with no indication of insulitis were found in the thymus of these 30 mice, whereas no grafted islets were found in the 2 mice that became diabetic at 17 and 19 weeks, respectively (technical failures). In the control group, 10 of 32 (31%) mice became diabetic between 20 and 29 weeks. This diabetic incidence was, however, lower than that in our colony female mice. In the pancreas of experimental mice, 90.9% of islets were free of infiltrates, whereas only 13.1% of islets were intact in control mice. The spleens of 30-week old experimental mice contained a slightly higher percentage of CD8+ T cells (P < 0.05) than those of control mice. Cyclophosphamide injections at 30 weeks induced diabetes in 4 of 9 experimental mice. The 2 lines of evidence, (1) marked reduction in insulitis of intrathymic islet-grafted mice and (2) induction of diabetes after treatment with cyclophosphamide, suggest that both thymic clonal deletion and peripheral tolerance may play a role in preventing diabetes. PMID- 8212163 TI - T cell subset responses to allogeneic endothelium. Proliferation of CD8+ but not CD4+ lymphocytes. AB - Endothelial cells were isolated from the hearts of neonatal mice and cocultured with syngeneic and allogeneic lymphocytes. T cells isolated by passage through nylon wool proliferated when cultured with allogeneic endothelium but not when cultured with syngeneic endothelium. This response was almost entirely confined to the CD8+ lymphocyte subset as purified CD4+ lymphocytes displayed a minimal response. Pretreatment of endothelial cells with recombinant murine gamma interferon induced expression of Ia but did not enable endothelial cells to activate CD4+ lymphocytes. Activation of CD8+ and T lymphocytes could be blocked with monoclonal anti class I antibody but was unaffected by anti-class II antibody. The failure to activate CD4+ lymphocytes was not due to suppression and did not lead to an anergic state. Instead, coculture of CD4+ cells with allogeneic endothelial cells induced a partial activation consisting of IL-2 receptor expression and accelerated secondary response kinetics. PMID- 8212165 TI - The synergism of brequinar sodium and cyclosporine used in combination to prevent cardiac allograft rejection in the rat. AB - Brequinar sodium (BQR) is a novel immunosuppressive drug that inhibits cell proliferation by virtue of its disruption of the de novo pyrimidine biosynthesis. The basis of the immunosuppressive activity of BQR is distinctively different from that of cyclosporine (CsA), and we have recently evaluated in vivo and in vitro the efficacy of the two drugs when used in combination. Subtherapeutic doses of BQR and CsA were tested for their ability to prolong heterotopic cardiac allograft survival in the MHC- and non-MHC-mismatched ACI-->LEW rat strain combination. The graft survival data derived from these experiments were analyzed using the median-effect analysis to establish the immunosuppressive interaction of both drugs. The administration of BQR 3 mg/kg three times weekly or CsA 2.5 mg/kg daily moderately prolonged cardiac allograft survival, with a mean survival of 10 +/- 0.5 and 16 +/- 5.3 days, respectively. The use of the two drugs in combination with the same dose schedule exerted a synergistic effect on graft survival, prolonging the graft function to a mean of 31 +/- 5.7 days. Sera from animals treated with the two drugs displayed, when compared with single treatment groups (BQR 3 mg/kg and CsA 2.5 mg/kg), significantly (P < 0.01) increased in vitro inhibition of lymphocyte proliferation following stimulation with PHA. Finally, a clear correlation between the mean survival time and BQR plasma levels of animals treated with BQR alone or in combination with CsA was seen. Those treatment groups with BQR levels below 2 micrograms/ml (1.5 and 3.0 mg/kg/3x/week) had a mean graft survival of less than 10 days). In contrast, recipients treated with a combination of low doses of BQR and CsA displayed higher drug plasma levels (> 2 micrograms/ml) and longer mean graft survival times. These observations suggest that BQR and CsA may be highly effective when used in combination to prevent organ allograft rejection for clinical transplantation. PMID- 8212164 TI - Reversal of ongoing heart, kidney, and pancreas allograft rejection and suppression of accelerated heart allograft rejection in the rat by rapamycin. AB - Rapamycin was examined for its effects on reversal of ongoing rejection of heart, kidney, and pancreas allografts and on suppression of accelerated heart allograft rejection in the rat. A 14-day continuous intravenous infusion of RAPA by an osmotic pump at 0.02, 0.08, and 0.8 mg/kg/day to WFu recipients, starting 4 days postoperation, significantly protected the BUF heart allografts with a mean survival time (MST) +/- 1 SD of 33.2 +/- 19.8 (p < 0.001), 48.2 +/- 14.8 (p < 0.001), and 107.0 +/- 86.3 (p < 0.001) days, respectively, as compared with 7.2 +/- 0.8 days in vehicle-treated controls. Combination of low dose RAPA (0.02 mg/kg or 0.08 mg/kg) and low dose CsA (2 mg/kg) achieved significantly longer cardiac allograft survival than RAPA or CsA alone. RAPA's effect in reversing ongoing rejection of renal and pancreatic allografts was also significant. The BUF kidney and pancreas in WFu recipients treated with a 14-day course of RAPA (0.8 mg/kg/day starting 4 days postoperation) had an MST of 44.7 +/- 15.9 (p < 0.001) and 46.4 +/- 12.5 (p < 0.001), while in vehicle-treated controls, the grafts were rejected within 10 days. RAPA could also suppress accelerated cardiac allograft rejection. Hyperimmunized WFu recipients were treated with two 14-day courses of continuous i.v. RAPA at 0.8 mg/kg/day before and after BUF heart allografting. Significantly longer survival of the grafts (25.5 +/- 3.7 days, p < 0.001) was achieved compared with that of the vehicle-treated controls (3.8 +/- 1.0 days). One-course RAPA treatment before or after heart transplantation was considerably less effective. RAPA was also shown to prevent the increase of serum IgG levels and to inhibit the production of specific cytotoxic Ab in the rat receiving repetitive immunizations. Such effects presumably contribute to the inhibition of the accelerated rejection. The results of this study suggest that RAPA is potentially useful in treatment of ongoing as well as accelerated allograft rejection. PMID- 8212166 TI - Assessment of proteinuria and neuropathy in the nonimmunosuppressed BB diabetic rat after abdominal intratesticular islet transplantation. AB - Only limited studies are available that assess diabetic complications following islet cell transplantation. Our objectives were to quantitate urine total protein, sural nerve morphometry, and sexual function in the diabetic BB/WOR male rat following islet cell transplantation into the abdominal testis. Success of islet cell transplantation was determined by nonfasting, morning, twice-weekly serum glucose and 12-hr fasting glucose, total glycosylated hemoglobin, and HbA1c after six months of diabetes and prior to death. Results showed that 9 of 16 rats were transplanted successfully for a period of at least six months. Pretransplant glucose was 21.9 +/- 4.67 (SD) mM/L and posttransplant glucose was 6.44 +/- 72 mM/L. The 12-hr fasting glucose ranged from 4.61 to 9.28 mM/L in animals prior to death, and glycosylated hemoglobins were not different from controls. Total urinary protein was significantly (P < 0.01) less than untreated diabetic rats (5.66 +/- 1.96 vs. 16.6 +/- 3.7 mg/24 hr) and not different from controls. Penile reflexes and serum testosterone remained normal in islet cell-transplanted animals. Sural nerve morphometry was normal, with 29.2% fewer abnormalities (paranodal swelling, paranodal demyelination, myelin wrinkling, Wallerian degeneration, and segmental demyelination) than untreated diabetic BB/WOR rats. We conclude that abdominal, intratesticular islet transplantation normalizes fasting blood glucose and glycosylated hemoglobin. In addition, the improvement in metabolic control at six months of diabetes was associated with normal total urinary protein, sural nerve morphometry, and sexual function. PMID- 8212167 TI - Expression of adhesion molecules in allograft renal dysfunction. A distinct diagnostic pattern in rejection and cyclosporine nephrotoxicity. AB - We have studied in thirty renal biopsies (from 30 cadaver allograft patients) the expression of both LFA-1 and VLA-4 leukocyte adhesion receptors and their respective ICAM-1 and VCAM-1 endothelial cell ligands, during early allograft dysfunction (24 +/- 5 days after transplantation), reversed either by antirejection therapy (n = 14) or by reduction in CsA dose (n = 16). We have found that the levels of expression of the integrin VLA-4 and the activation signal AIM/CD69 (activation inducer molecule) on interstitial cells were significantly (P < 0.001) higher in rejection than in nephrotoxicity. A main differential expression pattern was observed for VCAM-1, the endothelial cell ligand of VLA-4. Interestingly, a strong staining pattern of the renal vascular endothelium and 35% of tubular epithelium was obtained with anti-VCAM-1 antibody in rejection, as compared with a weak reactivity in endothelium and discrete staining pattern on tubules in nephrotoxicity. On the other hand, we found that the mean percentage of infiltrating cells bearing LFA-1 molecules and the intensity of ICAM-1 (a LFA-1 ligand) expression on endothelium were closely similar in both rejection and CsA nephrotoxicity. Nevertheless, a discrete significant (P < 0.05) "de novo" expression of ICAM-1 was present on tubular cells during rejection. Our results strongly suggest that in rejection the interstitial cell infiltrate seems to be facilitated by the contribution of both LFA-1/ICAM-1 and VLA-4/VCAM-1 cell adhesion mechanisms, and also that VLA-4/VCAM 1 leukocyte interaction does not play a role in cases with CsA nephrotoxicity. Furthermore, the differential expression patterns of VLA-4 and VCAM-1 molecules found between rejection and CsA nephrotoxicity could provide valuable immunohistochemical criteria in the diagnosis of allograft dysfunction. PMID- 8212168 TI - The frequency of pretransplant donor cytotoxic T cell precursors with anti-host specificity predicts survival of patients transplanted with bone marrow from donors other than HLA-identical siblings. AB - Transplantation with bone marrow from other than genotypically HLA-identical donors is associated with an increased incidence and severity of graft-versus host disease (GvHD). The precise influence of HLA incompatibilities is not easy to analyze as even perfectly matched, HLA-identical unrelated donors might still express HLA differences that remain undetected by conventional typing. To measure T cell activity against serologically detectable and nondetectable HLA antigens, we analyzed the frequencies of CTL precursors (CTLp) between 11 unrelated HLA matched and five related haploidentical donor/recipient pairs in graft-versus host direction. Our results show that whenever HLA class I disparities could be identified by serology, high precursor frequencies (1/28,000-1/94,000) were measured. In contrast, in donor/recipient pairs that differed for class II only, no precursors were detected. CTLp were elevated in two out of eight fully matched donor/recipient combinations. These combinations displayed activities as high (1/21,000; 1/52,000) as the combinations that were serologically HLA class I disparate. The incompatibilities detected by the cellular assay were highly significant for the clinical results after transplantation. High CTLp frequencies before transplantation correlated with unfavorable clinical results independent of the incidence of detected HLA differences. Five out of the six patients with high (> 1/100,000) CTLp frequencies died within 120 days after transplantation. GvHD IV was the cause of death for all (3/5) patients who had received an unmanipulated bone marrow. In the group with intermediate or undetectable CTLp frequencies, eight out of 10 patients are alive, seven (CTLp frequency undetectable) without GvHD more severe than grade II, while one patient (CTLp frequency = 1/180,000) suffered from GvHD grade III. One patient rejected the graft and was rescued by an autologous BMT. PMID- 8212169 TI - The effect of technical conditions and storage medium composition on the phosphomonoesters to inorganic phosphate ratio determined by 31P nuclear magnetic resonance spectroscopy in rabbit kidney. AB - Using 31P nuclear magnetic resonance spectroscopy, we compared the state of the high-energy phosphates in rabbit kidneys stored at 4 degrees C for 24 hr with 3 different solutions: Ringer (Rg), University of Wisconsin (UW), and Euro-Collins (EC) solutions. We found the highest phosphomonoester/inorganic phosphate (MP:Pi) ratio in the group of kidneys stored in the Rg solution (Rg, 0.93 +/- 0.04; UW, 0.36 +/- 0.02; EC, 0.28 +/- 0.02). This medium has been demonstrated in previous physiological studies to give poor results in terms of organ preservation compared to the solutions that mimic the "intracellular" fluid, such as the EC and UW solutions. Because the commonly used cold storage solutions contain phosphates, which superimpose on the intracellular Pi and, thus, can distort the results, we attempted to eliminate the contaminating solution around the kidney and in the vasculature by flushing the kidney with a phosphate-free solution (Rg). The MP:Pi ratio increased in the UW and EC groups (UW, 0.82 +/- 0.04; EC, 0.64 +/- 0.04) in identical proportion in the 2 groups. It remained highest in the Rg group (1.02 +/- 0.03). Comparisons of data before and after flush showed that external phosphate contamination was not predominant. There was no equilibrium in phosphate distribution between intra- and extracellular spaces at 24 hr of storage. We conclude that the validity of the MP:Pi ratio, as a viability index of renal transplant, might have to be restricted to comparisons of kidneys preserved in the same storage conditions. Therefore, it would be necessary to establish normal and pathological values of this ratio for each cold storage solution. PMID- 8212170 TI - Effects of bone marrow-derived natural suppressor activity on B cell responses to lipopolysaccharide. AB - Natural suppressor (NS) activity is detected in tissues undergoing intense hematopoietic regeneration. This includes the spleens of mice recovering from total lymphoid irradiation or cyclophosphamide treatment, or after induction of chronic graft-versus-host disease against minor histocompatibility antigens. NS cells are thought to act via an antiproliferative mechanism, based on the observation that NS cells inhibit thymidine ([3H]TdR) uptake by mitogen- or antigen-activated lymphocytes. In the present study, the mechanism of B cell inhibition by NS activity present in normal adult bone marrow is analyzed. [3H]TdR uptake of LPS-stimulated B cells is inhibited by the presence of bone marrow cells (BMC). Consistent with the decrease in DNA synthesis, cell cycle analysis reveals that the majority of B cells fail to exit G0. To determine whether cells in G1 are also susceptible to inhibition by BMC, we tested the ability of cells with NS activity to inhibit the LPS response of either low density B cells or B cells preactivated by LPS. Both populations of cells were readily inhibited in their uptake of [3H]TdR. Direct analysis of B cell growth in suppressed cultures demonstrates that B cell numbers remain constant, with only 6 30% of the control number of B cells present in cultures containing BMC. Taken together, these results indicate that the antiproliferative effect of NS cells is a result of not only resting B cells being inhibited from entering the cell cycle, but also the inhibition of B cells already in G1. PMID- 8212171 TI - In utero engraftment of fully H-2-incompatible versus congenic adult bone marrow transferred into nonanemic or anemic murine fetal recipients. AB - We have established a murine in utero bone marrow transplantation model system and have investigated the effects of donor strain differences, cell dose, and the number of injections on murine fetal survival and engraftment rates. In a series of experiments, 1221 nonanemic C57BL/6 fetuses were injected transplacentally on day 11 of gestation with 10(6) non-T-depleted adult bone marrow cells (BMC) from C57BL/6-CAST (congenic), BALB/c and DBA/1 (allogeneic) strains without recipient conditioning. Overall fetal survival was 45%, with a 4% engraftment rate in 475 evaluable day 5 newborns. Engrafted newborns initially had up to 75-100% donor peripheral blood cell engraftment, particularly with DBA/1 BMC. Surprisingly, a significantly (P < 0.05) higher incidence of engraftment was observed using allogeneic (5.2%) as compared with congenic donors (0.7%). However, engraftment in all groups was transient since engrafted recipients studied > or = 6 weeks post-natally had nondetectable levels of donor cells. In contrast, engraftment of congeneic marrow into anemic, stem cell-defective Wv/Wv recipients lead to a higher incidence (40%) of engraftment that persisted for > or = 6 weeks, increasing in the level of engraftment over time. Additional studies were performed in an attempt to further increase the incidence and permanence of engraftment. Neither doubling the cell dose nor doubling the number of injections improved engraftment rates in recipients of allogeneic bone marrow. Similarly, pretreatment of congeneic donors with 5-fluorouracil 4 days prior to harvesting marrow was not effective in increasing engraftment. Despite the inability to detect donor cells > or = 6 weeks postallografting, 2 of 10 evaluable recipients engrafted with DBA/1 BMC had specific and permanent (> 6 months observation time) tolerance to the donor skin graft with an intact capacity to reject third-party grafts. Thus short-term engraftment of allogeneic adult marrow stem cells can be successfully accomplished in a proportion of nonanemic fetal recipients. Engraftment of allogeneic donor cells can also lead to induction of a degree of tolerance in a proportion of recipients at maturity. These data form the basis of future studies directed toward understanding the mechanisms involved in in utero and postnatal marrow graft resistance, which will ultimately lead to designing strategies that will further enhance the permanence of engraftment with the use of adult marrow cells. PMID- 8212172 TI - MHC class I and II antigen expression on parathyroid cells and prospects for their allogenic transplantation. AB - Homologous parathyroid transplantation has been utilized with rare success in patients suffering from parathyroid hypofunction. Major factors determining the possibility for such transplantation comprise the hitherto essentially unexplored expression and inducibility of MHC class I and II antigens on parathyroid cells. Cryosectioned and dispersed normal human parathyroid tissue displayed no or very low immunohistochemical reactivity for both class I and II antigens on the parenchymal cells, whereas the adenomatous and hyperplastic parenchyma of pathological glands encompassed a higher expression of these antigens. Monolayer culture of parathyroid cells in the presence of IFN-alpha or IFN-gamma induced class I and II antigens on the abnormal but not on the normal parathyroid cells, and no detectable induction of these molecules was obtained by varying the extracellular calcium concentration. The results indicate that normal parathyroid cells may constitute candidates for allogenic transplantation, and that further studies on the modulation of MHC-coded molecules in these cells should facilitate the utility of this potential therapy. PMID- 8212173 TI - Increased frequency of alloantigen-reactive helper T lymphocytes is associated with human cardiac allograft rejection. AB - Endomyocardial biopsy (EMB) is the standard method of monitoring heart transplant recipients for the development of allograft rejection. To date, noninvasive methods to detect cardiac allograft rejection have lacked adequate sensitivity and specificity for wide clinical application. In this study, limiting dilution analysis (LDA) was used to quantitate the number of donor alloantigen-reactive helper T lymphocytes (HTLs) in the peripheral blood of cardiac transplant recipients. Cadaveric donor splenocytes were cryopreserved, providing a source of donor alloantigenic stimulation for these assays. Peripheral blood mononuclear cells were harvested from cardiac transplant recipients before transplantation and at the time of EMB. LDA of donor-reactive HTLs was conducted simultaneously on all time points to minimize experimental variation, and these data were related to EMB scores. Frequencies of donor-reactive HTLs in pretransplant samples were highly variable, ranging from 1/1381 to < 1/200,000, and correlated poorly with the degree of HLA disparity. During episodes of moderate rejection, donor-specific HTL frequencies increased an average of 6 times their post transplant baseline frequency. Additionally, 10-fold increases in HTL frequencies were seen preceding EMB-diagnosed rejection in several individuals. These data indicate that episodes of allograft rejection are associated with increases in the number of circulating donor-reactive HTL which are frequently detected before the development of histologically defined rejection. Thus, monitoring HTL frequencies may serve as a non-invasive method for detecting and predicting cardiac allograft rejection. Furthermore, this assay may provide a valuable means of assessing the in vivo efficacy of various immunosuppressive therapies. PMID- 8212174 TI - Transmission of Chagas' disease through cadaveric renal transplantation. PMID- 8212175 TI - Living-related liver transplantation despite major arterial and venous abnormalities. PMID- 8212176 TI - The use of intravenous gamma globulin for CMV prophylaxis. PMID- 8212177 TI - HIV, cyclosporine, and transplantation. PMID- 8212178 TI - Anemia and erythropoietin levels in recipients of solid organ transplants. The Multi-Organ Transplant Group. PMID- 8212179 TI - Local thrombolysis in a renal allograft threatened by renal vein thrombosis. PMID- 8212180 TI - Hypoaldosteronemic hyporeninemic hyperkalemia after renal transplantation. PMID- 8212181 TI - The relationship between calcium antagonist therapy and growth of T lymphocytes from human renal allograft biopsies. PMID- 8212182 TI - Recurrent postpartum renal failure in a renal allograft. PMID- 8212183 TI - Lymphoproliferative disorder of donor origin in a liver transplant recipient: complete remission after drastic reduction of immunosuppression without graft loss. PMID- 8212184 TI - Detection of IL-1 beta and TNF-alpha message and protein in renal allograft biopsies. PMID- 8212185 TI - The value of plasma-soluble interleukin 2 receptor monitoring in lung transplantation. PMID- 8212186 TI - Distribution of TCR alpha beta+ and TCR gamma delta+ lymphocytes in bronchoalveolar lavage from human lung transplant recipients. PMID- 8212187 TI - Intestinal transplantation in the mouse. PMID- 8212188 TI - Generation of lymphokine-activated killer cells with veto and natural suppressor activity from patients with leukemias and lymphomas. PMID- 8212189 TI - Orthotopic partial liver transplantation in the rat: a model of 70% hepatectomy and reduced size liver transplantation. PMID- 8212190 TI - Beneficial effect of aspirin and heparin in three-day dog kidney preservation. PMID- 8212191 TI - The immunomodulation of cryopreserved pancreatic islets by gamma irradiation. A feasibility study. PMID- 8212192 TI - The platelet-activating factor antagonist WEB 2170. Its beneficial effect on dog renal allograft survival. PMID- 8212193 TI - Protective role of asialo GM1+, NK1.1- cells in the occurrence of graft-versus host disease after total lymphoid irradiation. PMID- 8212194 TI - Specific intravenous carbohydrate therapy. A new concept in inhibiting antibody mediated rejection--experience with ABO-incompatible cardiac allografting in the baboon. AB - Heterotopic allografting of ABO-incompatible donor hearts in recipient baboons "hyperimmunized" against the incompatible A or B antigen (n = 3) was followed by hyperacute antibody-mediated vascular rejection within a mean of 19 min. The A and B epitopes against which these antibodies are directed are carbohydrates that can be synthesized. The continuous i.v. infusion of the specific synthetic A or B trisaccharide, beginning immediately pre-transplant and continued posttransplant for several days, prolonged allograft survival to a mean of 8 days (n = 2) and prevented antibody-mediated rejection, graft failure resulting from acute cellular rejection. The addition of triple pharmacologic immunosuppressive therapy (n = 4) resulted in prolongation of graft survival to a mean of > 28 days, with one heart still beating at 52 days; all grafts showed features of cellular rejection. "Accommodation" would appear to have developed in several baboons as graft function continued for periods of up to 39 days after discontinuation of carbohydrate therapy. Specific i.v. carbohydrate therapy should allow organ allografting to be performed across the ABO blood group barrier in humans. Furthermore, if the carbohydrate epitopes on the organs of discordant animals (e.g., the pig) against which human xenoreactive antibodies are directed can be confirmed, then this form of therapy might allow successful discordant organ xenotransplantation in man. PMID- 8212195 TI - Target antigens of hyperacute xenogeneic rejection in the rat to guinea pig to rat discordant combinations. AB - The increasing shortage in allografts has led to a renewed interest in xenogeneic transplantation. Discordant combinations are characterized by hyperacute rejection partly due to the presence of natural antixenogeneic antibodies in the recipient. The aim of this work was to characterize the target antigens, using 2 discordant models. In the rat into guinea pig model, analysis of organ homogenates by immunoblotting revealed numerous bands. Some of these bands were organ specific, whereas others, namely in the 55-kDa region, were detected in liver, heart, lung, and kidney. Using membrane extracts of liver cells or of aortic endothelial cells, only bands of 55 kDa were revealed. No band could be seen using extracts of isolated hepatocytes. Two bands of 55 kDa disappeared after preabsorption of guinea pig sera on the various rat tissue homogenates, suggesting that they represent xenoantigens common to these tissues. In order to investigate the in vivo relevance of these 55-kDa antigens, isolated rat livers were perfused with decomplemented guinea pig sera. Eluates revealed one single print of 55 kDa on rat tissue homogenates. Finally, preincubation of rat mononuclear cells with various xenogeneic sera did not inhibit the binding of mAb specific for rat class I or class II MHC antigens, suggesting that the latter are not recognized by natural xenoantibodies. In the guinea pig to rat model, the antigens detected had a molecular mass ranging from 95 to 110 kDa. Absorption and perfusion experiments also showed that these antigens were common to various tissues and involved in the binding of rat natural antibodies ex vivo. In conclusion, our results indicate that rat xenoantigens of about 55 kDa are recognized by guinea pig natural antibodies, while guinea pig xenoantigens of 95 110 kDa are bound by rat natural antibodies. These antigens are common to liver, heart, lung, and kidney, are borne by endothelial cells, and cannot be found on hepatocytes. PMID- 8212196 TI - Ex vivo characterization of human anti-porcine hyperacute cardiac rejection. AB - Hyperacute rejection (HAR) currently precludes the use of discordant organs for human transplantation. In order to comprehensively evaluate HAR in a clinically applicable species combination, we have developed an ex vivo perfusion model utilizing a neonatal extracorporeal membrane oxygenator circuit; this model allows for functional and sequential biopsy studies of working piglet hearts sustained by human, single donor AB+ type blood. A detailed description of the methods employed is included. Hearts perfused by allogeneic pig blood sustained normal function throughout the study period, while those perfused with human blood lost organized ventricular contraction in 25-34 min with markedly attenuated function. Compared with biopsies from piglet hearts perfused with allogeneic blood and biopsies taken prior to human blood perfusion (t = 0), biopsies of hearts perfused with human blood at t = 15 and 30 min demonstrated significant inflammatory changes involving vessels (endothelial and myointimal swelling and reaction) as well as myocardium (injury and necrosis). By immunohistology, significant vascular deposition of IgM, IgG, fibrinogen, C3, and C1q was seen, along with infiltrates of human leukocytes consisting predominantly of neutrophils, macrophages, and T cells, with occasional B cells and NK cells. Sequential studies of circulating blood demonstrated the progressive consumption of human leukocytes and human anti-porcine antibodies, but no decrease in complement activity as measured by CH50. These findings indicate that the rapid loss of function seen in human anti-porcine cardiac HAR is associated with deposition of IgM and IgG xenoreactive antibody and early complement components and that extensive infiltration by inflammatory cells occurs within 15-30 min. This model provides a useful system for the study of human anti-porcine HAR. PMID- 8212197 TI - Experimental graft arteriosclerosis. II. Immunocytochemical analysis of lesion development. AB - The development of progressive graft arteriosclerosis causes the majority of late deaths occurring in cardiac transplant recipients. The pathogenesis of this process remains unclear. In order to characterize the cellular composition of lesions progressively, we employed a model of graft arteriosclerosis in the rat involving untreated heterotopic cardiac allografts transplanted across minor histocompatibility barriers. Immunocytochemical studies were performed on arterial lesions in allografts removed at 15, 45, 75, and 120 days posttransplantation, using monoclonal antibodies specific for smooth muscle cells (HHF35, CGA7), monocytes/macrophages (ED1), T cells (W313), and endothelial cells (anti-vWf). We found areas of coronary intimal thickening demonstrated marked cellular heterogeneity. The earliest lesions involved the adherence of monocytes and T cells to the coronary endothelial surface. At later time points, we noted marked subendothelial accumulations of macrophages and occasional T cells in areas of intimal thickening. In contrast, smooth muscle cells were the major cell type identified in intimal lesions in 120-day-old allografts. Intimal macrophages are frequently seen in spontaneous human arteriosclerotic lesions; our findings suggest that macrophages, perhaps interacting with T cells, play an important role in the pathogenesis of graft arteriosclerosis. PMID- 8212198 TI - Functional and morphological assessment of rat aorta stored in University of Wisconsin and Eurocollins solutions. AB - University of Wisconsin (UW) and Eurocollins (EC) solutions are widely used for preservation of organs before transplantation. However, effect of storage solutions on vascular interface for transplant success is not known. In this study, we have used rat aorta as a model and assessed the effects of cold storage in UW and EC solutions on smooth muscle and endothelial function and the morphology. Smooth muscle and endothelial functions of the rat aorta were assessed using in vitro isometric tension measurement. Morphologic studies were done with scanning and transmission electron microscopy. No significant difference in contractile response to either norepinephrine (NE) or potassium chloride was observed between control aorta and aorta stored in UW solution for 1 hr or 24 hr. In contrast, sensitivity, but not the reactivity to NE and KCl, was increased in aorta stored in EC solution for 1 hr. If the tissues were stored in EC solution for 24 hr, both sensitivity and reactivity to NE and KCl were significantly reduced. Relaxatory response to acetylcholine, in endothelium intact vessels were reduced in aortas stored in EC solution, but not in UW solution. The magnitude of relaxations observed in tissues stored in the EC solution for 24 hr was less than in tissues stored for 1 hr. Sodium nitroprusside elicited similar relaxatory response in endothelium-denuded control tissue and in tissues stored in UW and EC solution. Electron microscopy data revealed marked swelling of the cell, loss of mitochondria and other intracellular organelles, and striking calcium deposits after preservation of the vessels in EC for 1 or 24 hr. In aorta stored in UW solution for 24 hr, endothelial and smooth muscle cells were intact, with moderate-size vacuoles in the cytoplasm. These results suggest that the UW solution is more suitable than EC solution for short-term preoperative storage of blood vessels. PMID- 8212199 TI - Effect of glycine in dog and rat liver transplantation. AB - Glycine has been shown to protect renal tubule cells and hepatocytes from ischemia, ATP depletion, and cold storage injury. Glycine may be a useful additive to organ preservation solutions or suppress reperfusion injury by infusion into recipients of liver transplantation. In this study, the effects of glycine on survival and postoperative liver injury were studied in the rat and dog orthotopic transplant model. Rat livers preserved for 30 hr in the University of Wisconsin (UW) solution were 50% viable (3 of 6 survivors for 7 days). When glutathione was replaced by 10 mM glycine, survival increased to 100% (6 of 6). There was a significant reduction in hepatocellular injury at the end of preservation (lactate dehydrogenase [LDH] in the pretransplant flush-out of the liver was lower in the glycine group) and after transplantation (serum LDH concentration 6 hr after transplant was lower in the glycine group). In the dog, omission of glutathione from the UW solution resulted in 33% survival (48-hr preservation model) versus 100% survival with glutathione. Replacing glutathione in the UW solution by glycine did not improve survival (33% after 48 hr of preservation). However, when glycine was given to recipients of livers preserved in the UW solution for 24 or 48 hr, there was a decrease in the degree of hepatocellular injury. After 48 hr of preservation, peak aspartate aminotransferase, alanine aminotransferase, and LDH were reduced by about 45-55% when glycine was given to the recipient. Although the differences, with and without glycine treatment of the recipients, did not reach statistical significance, there was a noticeable reduction in hepatocellular injury with glycine. There was 100% survival of dogs in the groups that received livers preserved with the UW solution plus or minus glycine infusion. Hepatamine, a parenteral nutrition solution containing glycine and other amino acids increased hepatocellular injury (higher concentrations of aspartate aminotransferase, alanine transferase, and LDH versus control 48-hr preserved livers), although all dogs survived. This study shows that glycine is cytoprotective when administered to recipients of livers preserved for 24 or 48 hr and suppresses hepatocellular injury, as reflected in a reduction in the concentration of serum enzymes. However, the differences, with and without glycine, were, at best, marginal and further studies are needed to determine whether glycine would make a significant improvement in liver preservation and prevent primary nonfunction. PMID- 8212200 TI - Factors influencing weight gain after renal transplantation. AB - Weight gain following renal transplantation occurs frequently but has not been investigated quantitatively. A retrospective chart review of 115 adult renal transplant recipients was used to describe patterns of weight gain during the first 5 years after transplantation. Only 23 subjects (21%) were overweight before their transplant. Sixty-six subjects (57%) experienced a weight gain of greater than or equal to 10%, and 49 subjects (43%) were overweight according to Metropolitan relative weight criteria at 1 year after transplantation. There was an inverse correlation between advancing age and weight gain, with the youngest patients (18-29 years) having a 13.3% weight gain and the oldest patients (age greater than 50 years) having the lowest gain of 8.3% at 1 year (P = 0.047). Black recipients experienced a greater weight gain than whites during the first posttransplant year (14.6% vs. 9.0%; P = 0.043), and maintained or increased this difference over the 5-year period. Men and women experienced comparable weight gain during the first year (9.5% vs. 12.1%), but women continued to gain weight throughout the 5-year study (21.0% total weight gain). The men remained stable after the first year (10.8% total weight gain). Recipients who experienced at least a 10% weight gain also increased their serum cholesterol (mean 261 vs. 219) and triglyceride (mean 277 vs. 159) levels significantly, whereas those without weight gain did not. Weight gain did not correlate with cumulative steroid dose, donor source (living-related versus cadaver), rejection history, pre-existing obesity, the number of months on dialysis before transplantation, or posttransplant renal function. Posttransplant weight gain is related mainly to demographic factors, not to treatment factors associated with the transplant. The average weight gain during the first year after renal transplantation is approximately 10%. This increased weight, coupled with changes in lipid metabolism, may be significant in terms of altering risk from cardiovascular morbidity. PMID- 8212201 TI - A prospective randomized comparison of quadruple versus triple therapy for first cadaver transplants with immediate function. AB - In January 1988, we initiated a prospective, randomized comparison of prophylactic antilymphoblast globulin (ALG; quadruple therapy) versus no prophylactic ALG (triple therapy) in the setting of immediate graft function (defined by a brisk diuresis and a 20% decline in serum creatinine within 24 hr). Recipients were stratified according to presence of diabetes and age greater or less than 50 years. Recipients on quadruple therapy (n = 61) received 7 days of prophylactic Minnesota ALG (5 mg/kg on day 1, 10 mg/kg on day 2, 20 mg/kg on days 3-7). CsA, 10 mg/kg/day, began on day 6. AZA began at 2.5 mg/kg/day and was adjusted according to white blood cell count. Recipients on triple therapy (n = 60) began immediate CsA, 10 mg/kg/day orally and AZA, 5 mg/kg/day, tapering to 2.5 mg/kg/day by day 8. Both groups received identical prednisone tapers beginning at 1 mg/kg/day, decreasing to 0.5 mg/kg/day by 2 weeks and to 0.15 mg/kg/day by 6 months. Demographic characteristics between groups were not different with respect to diabetes, age, sex, race, per cent panel-reactive antibodies (PRA), or HLA matching. Follow-up ranged from 2 to 4.5 years. Patient survival was 93% for the quadruple therapy group and 90% for triple therapy. Actuarial graft survival was 79% in the quadruple group and 72% in the triple group (P = 0.18). Graft loss due to rejection occurred in 6/61 receiving ALG versus 7/60 in the immediate CsA group. Three of 4 high PRA recipients in the immediate CsA group lost their grafts within 30 days compared with none in the ALG group. The mean time to graft loss was significantly longer for the quadruple therapy group (17 +/- 8 months) compared with the triple therapy group (4 +/- 5 months), P = 0.006. The total number of rejection episodes was similar for both groups (29/61 vs. 31/60), as was the number who were rejection free (51% vs. 47%). The use of OKT3 was also similar between groups (28% vs. 30%). The quadruple therapy group had a higher incidence of CMV infection: 20% vs. 7% (P < 0.05), but no grafts or patients were lost as a result. Serum Cr was not different at 1 and 12 months (1.5 and 1.6 vs. 1.6 and 1.7, respectively), nor were Cr clearances (63 and 68 vs. 60 and 63). Conclusion. Early initiation of oral CsA in the setting of immediate graft function is not associated with significant nephrotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8212202 TI - Serum and urine IL-6 and TNF-alpha in renal transplant recipients with graft dysfunction. AB - The object of the study presented here was to test whether measurement of blood or urine IL-6 or TNF-alpha could discriminate between the most common causes of renal allograft dysfunction, thus avoiding a biopsy. We present data here in which serum and urine IL-6 and TNF-alpha levels were measured at the same time as a diagnostic renal biopsy was performed. TNF-alpha and IL-6 were measured by sandwich ELISA. Thirty patients had acute cellular rejection, 18 had acute tubular necrosis/CsA toxicity, and 9 had chronic vascular rejection. There was no difference in the levels of IL-6 measured in serum and urine among the three categories of graft dysfunction (t < 1.31; P > 0.20). A similar result with considerable overlap between the groups was seen with TNF-alpha (t < 0.78; P > 0.44). Stratifying the results according to the precise immunosuppressive therapy, CsA dose, body weight, CsA level, body temperature, serum creatinine, the number of previous rejection episodes, original cause of renal failure, or the time elapsed since the transplant did not alter the results. The ratio of serum IL-6 divided by trough CsA level was compared among the three groups and there was no significant difference among them (t < 1.79; P > 0.09). In the light of our results, we therefore suggest that previously published reports of the clinical value of serum and or urine IL-6 and or TNF-alpha in relatively small numbers of patients, not all of whom had been biopsied and in whom rigorous clinical and statistical criteria had not been met, should be viewed with caution. PMID- 8212203 TI - Parvovirus B19 infection in pediatric transplant patients. AB - Evidence of recent parvovirus virus infection (as determined by the presence of a positive IgM antibody titer) without other identified causes of anemia was found in 5 of 26 pediatric solid-organ transplant recipients evaluated for moderate-to severe anemia between June 1990 and July 1991. Anemia tended to be chronic (median duration of anemia at the time of diagnosis was 12 weeks) and was associated with normal red blood cell indices in the absence of reticulocytes. The median age of the children at the time of presentation with anemia due to parvovirus was 1.8 years at a median time of 8 months after transplantation. Four of the 5 children were treated with i.v. immunoglobulin because of persistence of anemia requiring blood transfusions. A response characterized by an increase in reticulocyte count and normalization of hemoglobin was seen in each of these patients 2-4 weeks after treatment. The remaining patient experienced a spontaneous recovery from her anemia. Parvovirus infection should be included in the differential diagnosis of solid-organ transplant recipients presenting with severe anemia associated with low or absent reticulocytes. PMID- 8212204 TI - Fate of renal allografts transplanted in patients with urinary diversion. AB - Fifty-five kidneys were transplanted into 50 patients with supravesical urinary diversion at 16 transplant centers between 1970 and 1991. Of the 32 males and 18 females, 40 were adults (> or = 18 years) and 10 were less than 18 years old at the time of first transplant. Mean follow-up was 7.8 years. At last follow-up, 94% of recipients were alive and 73% of the kidneys were functioning. Fifteen kidneys were lost: 9 to rejection, 3 to noncompliance, and 3 patients died with a functioning kidney. Ten (18%) transplants were followed by surgical complications. Twenty-four (44%) were followed by medical complications of which urinary tract infection was most common. Recipients age 18 or younger had more urinary tract infections than older patients. No patient had urinary stones and no patient required medical treatment for metabolic abnormalities. We conclude that drainage of kidney transplants into a supravesical urinary diversion is an effective treatment for end-stage renal disease patients without adequate urinary bladders. PMID- 8212205 TI - Effect of daily oral vitamin D and calcium therapy, hypophosphatemia, and endogenous 1-25 dihydroxycholecalciferol on parathyroid hormone and phosphate wasting in renal transplant recipients. AB - Ten stable, normocalcemic renal transplant patients with good allograft function, hyperparathyroidism, and variable hypophosphatemia were treated for 2 to 9 months with oral calcium carbonate and replacement doses of vitamin D analogues. Parathyroid hormone levels (PTH) and renal phosphate wasting were not autonomous or fixed but decreased with therapy. Although serum 1-25(OH)2D3 levels could be shown to rise appropriately during oral vitamin D therapy and fall afterwards, a separate study in a larger group of patients showed no effect of elevated parathyroid hormone or hypophosphatemia to increase endogenous 1-25(OH)2D3 levels. Some 42% of patients with elevated carboxy-terminal PTH, had elevated N terminal PTH, which was closely associated with more severe phosphate wasting. Aggressive oral calcium and vitamin D supplementation in certain normocalcemic renal transplant patients may decrease endogenous PTH levels, improve hypophosphatemia, and provide a physiologic increase in levels of 1-25(OH)2D3. PMID- 8212206 TI - The cost-effectiveness of preservation with UW and EC solution for use in cadaveric kidney transplantation in the case of single kidney donors. AB - University of Wisconsin (UW) solution is now commonly used as a single-flush solution during multiorgan procurement for effective preservation of all intraabdominal organs including the kidney. Many kidneys from single kidney donors are still preserved in Eurocollins solution and the question is whether preservation in UW solution is more cost-effective. A European randomized multicenter trial was organized by the Department of Surgery of Leiden University in close cooperation with Eurotransplant to study the efficacy of UW solution as compared with EC solution. On the basis of this trial we found that at three months after transplant 92.4% of the patients in the UW group had a functioning graft in comparison with 88.4% in the EC group (similar figures after one year were 88.2% and 82.5%, P approximately 0.04), while health care expenditure during these first three months was on average US$ 700 lower for the UW group than for the EC group, taking into account the price difference in the preservation fluids. The long-term benefits of using UW solution as compared with EC solution were conservatively estimated at US$ 7000 per patient reflecting the additional expenses for dialysis in the EC group. We concluded that the extra costs of using UW solution instead of EC solution (US$ 230 per kidney) can be easily earned back within three months and that the long-term savings of such a strategy are considerable. Moreover, the health status of patients in the UW group is expected to be better on the average than in the EC group. Simply reacting to the price tag of the UW solution may be penny-wise but pound-foolish. PMID- 8212207 TI - Alterations in plasma magnesium concentrations during liver transplantation. AB - Plasma magnesium concentrations were monitored during orthotopic liver transplantation. Magnesium supplementation was not given, although intraoperative calcium, potassium, and sodium bicarbonate were given as required. We found that there were significant falls in magnesium concentration to below our laboratory lower limit of normal, occurring chiefly during the anhepatic phase of surgery. Two patients with hypomagnesemia but normal potassium and calcium ion concentrations developed ventricular extrasystoles. Magnesium is a smooth muscle relaxant, dilating coronary arteries and peripheral vessels. It also exerts an antiarrhythmic effect and may have a permissive effect on the actions of catecholamines. Magnesium supplementation may be indicated during orthotopic liver transplantation because of the potentially beneficial effects and to avoid possible deleterious effects of hypomagnesemia. However, magnesium levels need to be monitored to avoid the unwanted side effects of hypermagnesemia. PMID- 8212208 TI - Provision of prognostic information in immunocompromised patients by routine application of the polymerase chain reaction for cytomegalovirus. AB - A polymerase chain reaction (PCR) assay that amplifies a 149 base pair fragment of the cytomegalovirus glycoprotein B gene was used in the routine screening of 548 urine and 248 blood specimens from immunocompromised patients. The PCR results were compared with those obtained for the same specimens tested by the methods of conventional cell culture (CCC) and detection of CMV-specific immediate-early antigen fluorescent foci (DEAFF). For both urine and blood, PCR positivity correlated with a positive result in CCC (urine 93.2%; blood 86%). As expected for a more sensitive assay, PCR also identified CMV in samples that were negative by CCC and DEAFF such that there was no concordance between tests (Kappa test P > 0.05). The sensitivity, specificity, positive predictive value, and negative predictive values of PCR positivity in blood with respect to CMV disease were 0.8, 0.86, 0.62, and 0.94, respectively, with an associated relative risk of 5.84 (95% CI; 3.2-10.8). PCR detection of CMV in urine was more sensitive than either DEAFF or CCC (0.6 vs. 0.35 and 0.5, respectively) and had a high negative predictive value (0.89) but the positive predictive value was lower than either CCC or DEAFF (0.32 vs. 0.41 and 0.37, respectively) with respect to disease. Longitudinal data on patients with disease showed that CMV in blood was detected at a median of 5 days (range; -20 to +3 days) before disease onset whereas CMV was detected by CCC at a median of 13 days (range -4 to +20 days) after disease onset. In addition, the PCR assay was integrated into the battery of tests routinely performed on transplant patients in the diagnostic laboratory at this institution. PMID- 8212209 TI - Demonstration of cytomegalovirus by polymerase chain reaction after liver transplantation. AB - The polymerase chain reaction (PCR) is a highly sensitive and specific technique for detection of cytomegalovirus DNA. With this method we prospectively analyzed buffy coat leukocytes at weekly intervals over 3 months in 60 patients after liver transplantation (LTX). The PCR results were correlated with the pretransplant donor/recipient CMV antibody status and with the occurrence of CMV induced disease. Thirty-three of 60 (55%) patients became PCR-positive during their posttransplant course. None of the 27 patients with permanent negative PCRs developed CMV disease. Of 33 patients with positive PCRs, 13 (39%) became ill. CMV disease developed in 9 of 22 (41%) antibody-negative recipients but only in 4 of 38 (10%) seropositive graft recipients. The incidence of CMV disease was 75% (9 of 12 patients) in seronegative recipients who converted to positive PCR results and 19% (4 of 21 patients) in seropositive patients with positive PCR findings. The predictive value of a positive PCR was 75% in seronegative patients but it was low (19%) in seropositive recipients. The predictive value of a negative PCR is 100%. Thus, PCR determinations are useful in identifying patients who will not develop CMV disease and in narrowing down the number of individuals who will become sick. Further, PCR is a helpful tool in the follow-up of patients under antiviral treatment. PMID- 8212210 TI - Hemorrhagic cystitis after bone marrow transplantation. Risk factors and complications. AB - Hemorrhagic cystitis (HC) is a major cause of morbidity after BMT; we have analyzed its incidence, risk factors, and complications in 977 patients undergoing BMT between 1974 and 1988. Despite vigorous hydration and frequent voiding in all patients receiving cyclophosphamide, 135/977 (15% by Kaplan-Meier projection) developed HC (micro- or gross hematuria, dysuria, bladder pain) between -11 and +100 days (median +22) after BMT. Of these, 60 had severe HC, including major urinary obstruction (4/60), renal failure (13/60), or need for surgical or chemical bladder cauterization (16/60). By univariate analysis, allogeneic BMT recipients had more frequent HC than autologous patients (17% vs. 9%, P = 0.002). In addition, allogeneic patients with adenoviruria were at increased risk for the development of HC. Patients with aplastic anemia conditioned with high dose cyclophosphamide and total lymphoid irradiation had the highest rate of HC (22%) versus those with hematologic malignancies (15%, P = 0.03). A Cox proportional hazards regression model was used to further identify those factors independently associated with HC. In all regression models, the factor most highly associated with the development of HC was the finding of adenovirus in the urine preceding the onset of hematuria. HC-related morbidity, and its associated increased hospitalization costs, frequently complicates BMT. Improved prophylactic measures, perhaps including the use of 2-mercaptoethane sulfonate, are needed, at least for allogeneic BMT patients with their attendant risk of adenovirus infection. PMID- 8212211 TI - Cyclosporine-induced elevation in circulating endothelin-1 in patients with solid organ transplants. AB - The long-term use of cyclosporine is associated with significant complications, including hypertension and renal failure. Recent data from animal experiments suggest that alterations in renal function induced by high-dose CsA may be mediated by endothelin-1 (ET-1), a potent endothelium-derived vasoconstrictor and mitogenic peptide. The aim of the present study was to determine the effect of oral CsA on circulating levels of ET-1 in patients receiving standard immunosuppressive therapy following solid-organ transplantation (13 renal, 7 heart, 1 heart-lung, 1 liver). Plasma levels of ET-1 were measured by radioimmunoassay over a 24-hr period beginning with the oral administration of a single daily dose of CsA in 18 patients (5.6 +/- 0.5 mg/kg), or similar immunosuppressive therapy without CsA in 4 patients. Blood levels of CsA (parent compound and metabolites) were measured in 10 of the patients by RIA. Predose levels of ET-1 were similar in the two groups (1.73 +/- 0.32 and 1.29 +/- 0.9 pg/ml, respectively). Patients not receiving CsA showed no change in plasma ET-1 over the 24-hr period. In contrast, in the CsA-treated group there was a significant increase in plasma ET-1, reaching a peak at 6 hr (2.45 +/- 0.56 pg/ml, P < 0.03) that followed the peak increase in CsA parent compound and preceded the peak increase in metabolites. No significant differences were found between peak and trough levels of ET-1 in patients with moderate renal dysfunction (creatinine (Cr) > or = 150 mumol/L) compared with those with near normal renal function, or patients receiving renal compared with nonrenal grafts. However, patients with long-term grafts (> 60 days) showed an exaggerated response to CsA, with a fractional increase in plasma ET-1 of 3.67 +/- 0.52 (n = 8) compared with 2.16 +/- 0.28 (n = 10) for patients with more recent grafts (P < 0.05). Therefore, oral administration of CsA causes an increase in circulating ET 1 in patients with solid-organ transplants that might contribute to CsA associated nephrotoxicity and hypertension, particularly during long-term immunosuppressive therapy. PMID- 8212212 TI - Cyclosporine-induced stimulation of the renin-angiotensin system after liver and heart transplantation. AB - To analyze the status of the renin-angiotensin system in hypertensive transplant recipients on cyclosporine, we prospectively explored 21 cardiac (CTR: 52 +/- 8.2 yr) and 12 liver (LTR: 45 +/- 10 yr) transplant recipients on a normal salt diet with 19 normotensive controls in the same age range. Systolic and diastolic blood pressure was measured in the supine and standing positions. Renal function was assessed by serum creatinine values, and 24-hr urinary sodium and potassium excretion were recorded. Plasma renin activity (PRA), active renin, total renin, angiotensinogen, aldosterone, and cortisol plasma levels were simultaneously determined. Results were expressed as mean +/- SD, and between-group differences were compared using variance analysis. Supine blood pressure (+/- SD) was 158 +/- 15/103 +/- 8.4 in CTR and 155 +/- 21.4/102 +/- 11.7 mmHg in LTR. Serum creatinine was higher in CTR (159 +/- 52 mumol/L) than in LTR (117 +/- 24.7, P < 0.05) and values in both groups were above controls (83 +/- 14.1, P < 0.05). Urinary sodium excretion tended to be lower in transplant recipients (59 +/- 42 mmol/L) for CTR and 44 +/- 36.7 in LTR than in healthy controls (117 +/- 24.7 mmol/L). Supine and upright PRA values tended to be higher in hypertensive transplant recipients than in healthy volunteers, although not significantly. Supine active renin was significantly higher in CTR (47 +/- 42 pg/ml) and in LTR (44 +/- 29.8 pg/ml) than in normal subjects (17 +/- 4.8 pg/ml, P < 0.05). Total renin levels in CTR (supine: 716 +/- 357 pg/ml) and in LTR (supine: 647 +/- 365 pg/ml) were 3- to 4 fold higher than in controls (supine: 207 +/- 69 pg/ml) (P < 0.05), as were inactive renin levels (P < 0.01). Active renin was effectively correlated with PRA (P < 0.001) and with total renin (P < 0.001) in the supine and in the upright position. Plasma aldosterone was almost within the normal range in CTR and in LTR, and it did not correlate with PRA values. Plasma angiotensinogen levels were normal in LTR (1032 +/- 226 ng/ml) but were significantly lower in CTR (938 +/- 216 ng/ml, P < 0.05). Cortisol plasma levels were lower in both CTR (7 +/- 4.4 micrograms/L) and LTR (6 +/- 1.9 micrograms/L) than in healthy controls (11 +/- 4 micrograms/L, P < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8212213 TI - CD4-positive helper T lymphocytes mediate mouse cardiac allograft rejection independent of donor alloantigen specific cytotoxic T lymphocytes. AB - Mouse heterotopic cardiac allograft recipients were depleted of CD4+ or CD8+ T lymphocytes in vivo to assess cellular requirements for graft infiltration, tissue damage, and acute allograft rejection. Modified limiting dilution analysis was employed to quantitate IL-2-producing Th lymphocytes (HTL) and CTL infiltrating the graft. Results were correlated with graft function and histologic evidence of tissue damage. In unmodified recipients, large numbers of donor alloantigen-specific CTL infiltrated the graft, overshadowing a modest number of HTL. CTL infiltration coincided with tissue damage and loss of graft function, suggesting a key role for CTL in rejection. In vivo treatment with anti CD4 mAb inhibited both HTL and CTL infiltration, and no histologic evidence of tissue damage was observed. This observation suggested that HTL, although few in number, regulated the development of effector CTL and/or entry of these CTL into the graft. Reconstitution of HTL-depleted recipients with IL-2 resulted in graft infiltration by stimulated CTL, as assessed by modified limiting dilution analysis. However, these stimulated CTL failed to mediate tissue damage, and graft survival was prolonged. Unlike CTL obtained from unmodified recipients, graft-infiltrating CTL of IL-2-reconstituted mice were incapable of directly lysing donor cells in a 51Cr release assay. Hence, while IL-2 facilitated partial CTL differentiation and mobilization to the graft, additional signals appear necessary for maturation into lytic CTL. Furthermore, in recipients depleted of CTL by treatment with anti-CD8 mAb, HTL infiltrating the allograft, though few in number, were associated with extensive tissue damage and loss of graft function. These data suggest a less important role for CTL in the rejection process, and indicate that graft-infiltrating CTL are insufficient as sole mediators of cardiac allograft rejection. Potential mechanisms by which CD4+ HTL mediate cardiac allograft rejection independent of CTL are discussed. PMID- 8212214 TI - The prevention of accelerated cardiac allograft rejection in sensitized recipients after treatment with brequinar sodium. AB - Brequinar sodium (BQR) is a novel immunosuppressive agent that is highly effective in preventing B lymphocyte-mediated antibody production. We have examined the effects of BQR treatment in sensitized recipients on graft survival, donor-specific antibody responses (IgM and IgG), and the appearance of immunopathological lesions present in the grafts. LEW rat recipients were sensitized with single ACI skin graft on day 7 and received heterotopic ACI cardiac grafts on day 0. The recipients rejected the cardiac grafts in an accelerated fashion at day 2.5 post-transplantation, compared to day 7.0 in unsensitized recipients. The animals were treated with low (3 mg/kg/day) or high (12 mg/kg/3x weekly) doses of BQR during skin graft sensitization and/or after challenge with ACI heart allografts. All groups treated with BQR showed significant prolongation of graft survival in the sensitized recipients. The best survival was observed following high-dose BQR therapy during both sensitization and effector phases (median survival time = 40.0 days, P << 0.001). Daily treatment with BQR (3 mg/kg/day) prevented IgM (but not IgG) antibody responses. Treatment with higher doses of BQR (12 mg/kg/3x weekly) before and after skin graft sensitization was effective in preventing both IgM and IgG production. In general, BQR treatment resulted in effective suppression of anti-donor antibody responses, stable graft function, and a reduction in the severity of the acute vascular lesions in the graft. The effectiveness of BQR in preventing accelerated graft rejection when used at 12 mg/kg/3x weekly was comparable to that seen with treatment of sensitized animals with CsA at 15 mg/kg/day for 30 days. Daily treatment with cyclophosphamide at 5 or 15 mg/kg/day was ineffective for preventing graft rejection in sensitized recipients. These results indicated that BQR may provide an important addition to treatment protocols designed to prevent transplantation rejection in presensitized patients. BQR has the ability to significantly inhibit host cellular and humoral immune responses to the donor graft and this facet of the immunosuppressive activity of the drug may be responsible for preventing this aggressive form of rejection. PMID- 8212215 TI - Evidence for early Th 2 T cell predominance in xenoreactivity. AB - Two distinct subsets of CD4+ Th lymphocytes have been characterized by their cytokine profiles: Th 1 (TH1) and Th 2 (TH2). While TH1 cells predominate in cell mediated responses, TH2 cells support the humoral response. We have examined the mRNA cytokine profile of normal mouse lymphocytes in response to alloantigen versus xenoantigen (rat) in MLC, and present evidence to suggest that early in proliferative responses, alloreactivity is dominated primarily by TH1-type lymphocytes, while xenoreactivity is predominantly TH2. Normal mouse lymphocyte responding cells were cultured in a one-way MLR with either allo or xeno antigen and examined for production of mRNA for cytokines characteristically produced by TH1 (IL-2, IFN-gamma) or TH2 (IL-4, IL-10) cells. Semiquantitative reverse transcription-polymerase chain reaction analysis was performed for mouse IL-2, IL 4, IL-10, and IFN-gamma mRNA. In the mouse anti-rat xeno response, mRNA for TH2 gene products were upregulated, with greater levels of IL-4 and IL-10 at 24 and 48 hr when compared with controls. In contrast, upregulation of mRNA for TH1 gene products occurred in the mouse anti-mouse allo response, with higher levels of IL 2 and IFN-gamma at 24 and 48 hr. In the anti-xeno response, upregulation of all 4 cytokines occurred by day 4 and peak levels of mRNA for all cytokines examined were 2-3 times that seen for the peak anti-allogeneic response. These data suggest that early xenorecognition may differ from allorecognition by differential activation of the TH2 subset. A better understanding of the balance between Th subset function and cytokine profile in allo and xeno reactivity may allow a more targeted and specific approach to control the early events in xenograft rejection. PMID- 8212216 TI - A long-term study of allogeneic rat hindlimb transplants immunosuppressed with RS 61443. AB - Although technically possible, limb allotransplantation has not been applied clinically. The skin component is especially antigenic, requiring high immunosuppressant doses with an unacceptable toxicity profile. RS-61443, an experimental mycophenolic acid ester that inhibits lymphocyte proliferation without major systemic toxicity, was tested as an immunosuppressant to prevent rejection of rat hindlimb allotransplants. Utilizing Brown-Norway donors and F344 recipients to provide a major mismatch at the MHC, midfemur orthotopic limb transfer was performed with microsurgical repair of femoral vessels and sciatic nerve. Four primary groups were studied: autografts (n = 4); untreated allografts (n = 6); allografts receiving CsA 10 mg/kg for 20 days, then twice per week (n = 6); and allografts receiving RS-61443 30 mg/kg/day (n = 6). Skin and soft tissues were biopsied to assess rejection. Autografts had indefinite limb survival, while untreated allografts had complete acute rejection within 10-12 days. Five of the six CsA rats developed delayed mild-moderate acute rejection within 6 months. In contrast, 5 of the 6 RS-61443 rats had no rejection after at least 32 weeks, while the sixth rat developed only slight rejection on skin biopsy. All animals regained full sensation and partial functional return. RS-61443 is highly effective as a primary immunosuppressant for hindlimb allotransplantation. The disturbing moderate rejection observed in CsA animals, which was absent with RS 61443, may significantly hamper function of transplanted limbs. PMID- 8212217 TI - The correlation of prolonged survival of maternal skin grafts with the presence of naturally transferred maternal T cells. AB - Hypoimmune responses towards noninherited maternal MHC antigens (NIMA) have been observed on both the humoral and cellular level in humans. The mechanism involved is not known but is thought to involve transfer of material from mother to child. Here we use a mouse model to test this hypothesis. Mice exposed to NIMA either in utero and/or via breast milk showed enhanced survival of maternal skin grafts and also had maternal lymphocytes in their lymph nodes. Survival of the maternal skin graft correlated with the number of maternal T cells present and was not correlated with the number of maternal B cells. We propose that the transferred maternal T cells selectively inactivate host T cells capable of recognizing them. PMID- 8212218 TI - H-2-specific T suppressor cells. I. Evidence for T suppressor inducer and effector molecules in suppression. AB - The induction of H-2-specific Ts cells was accomplished by the i.v. injection of X-irradiated (2000R) C57BL/6 spleen cells into CBA/J mice. These Ts cells significantly (78%) suppressed the delayed type hypersensitivity (DTH) response in CBA/J mice injected s.c. with X-irradiated (2000R) C57BL/6 spleen cells and given a footpad challenge with the same cell population 5 days later. We have shown that both CD4 and CD8 T cells were involved in the observed suppression, and these cells secrete T suppressor inducer (Tsfi) and T suppressor effector (Tsfe) molecules. Both Tsfi and Tsfe molecules were shown to significantly inhibit (> 87%) one-way mixed lymphocyte responses between CBA/J and mitomycin C treated C57BL/6 spleen cells. Using an adoptive transfer method, we showed that mice given both a primary and secondary immunization with X-irradiated C57BL/6 spleen cells to induce H-2-specific Ts cells contain a significantly greater number of Ts cells than mice given only a primary immunization, suggesting the presence of memory Ts cells. PMID- 8212220 TI - Cross-species graft-versus-host-disease is accompanied by a donor-derived cellular immune response. AB - Acute graft-versus-host-disease is classically described as reactivity of donor lymphocytes to recipient alloantigens. To date there is debate as to whether GVHD can be induced across a species barrier. We recently reported the induction of stable xenogeneic chimerism (rat-->mouse) and donor-specific transplantation tolerance using the transplantation of untreated rat bone marrow cells into B10 mouse recipients. Survival of chimeras was excellent, and there was no evidence of GVHD. We now describe the induction of xenogeneic GVHD by transplanting large numbers of donor rat spleen cells with the bone marrow inoculum. All chimeras that received bone marrow and untreated spleen cells developed an external appearance compatible with GVHD and had a median survival time of 14 days. Mice that received equivalent numbers of untreated rat bone marrow alone appeared healthy, had no evidence for GVHD, and survived > 90 days. The usual epithelial target tissues for allogeneic GVHD in those mice that received xenogeneic bone marrow and spleen cells showed the presence of tissue injury and histologic features compatible with GVHD. Donor rat MHC class I and class II positive cells were prominent cell types present in the tongues of mice that developed features of GVHD, and this was accompanied by a significant inflammatory tissue response with loss of the dermal-epidermal architecture. In contrast, fully xenogeneic chimeras without GVHD had no evidence for tissue injury or pathologic cellular infiltrates when examined by immunohistochemical analysis. These data suggest that although fully xenogeneic chimeras resist GVHD, GVHD can be induced across a species barrier if sufficient numbers of donor rat spleen cells are added to the bone marrow inoculum. Further comparisons of these models may provide an approach to study the mechanisms responsible for xenoreactivity in vivo. PMID- 8212219 TI - Immunosuppressive effects of defibrotide. AB - The effect of defibrotide (DF) alone or in combination with CsA was examined using in vitro proliferation assays with human PBLs and in vivo heterotopic heart allografts in rats. DF alone (12.5-50 mg/ml) inhibited in vitro PBL proliferation more effectively after PHA (50-56%) or OKT3 (50-95%), than after alloantigenic (25-30%), stimulation. Furthermore, the combination of DF (1-4 mg/ml) with CsA (10-40 ng/ml) caused an 85.2-86.8% reduction in proliferative responses after OKT3 stimulation. Median-effect analysis documented that the combination index for DF and CsA was consistently lower than 0.3 at various concentration ratios of the 2 agents. Combination index values below 1.0 reflect drug synergism; those equal to 1.0 show additive, and above 1.0, antagonistic, interactions. Daily intraperitoneal injections of DF (150 mg/kg) failed to prolong the survival of Buffalo (RT-1b) heart allografts in Wistar-Furth (RT-1u) recipients, namely mean survival times of 7.0 +/- 0.7 days with, vs. 6.5 +/- 0.5 days without, DF treatment. Similarly, intravenous or intra-arterial infusion of DF (280 mg/kg) delivered directly into the heart allograft by a 7-day osmotic pump was ineffective. However, a course of local, but not systemic, DF (280 mg/kg) combined with a 14-day i.v. administration of a subtherapeutic dose of CsA (1 mg/kg) significantly prolonged heart allograft survival to 22.8 +/- 5.0 days (P < 0.001). Thus, in vitro DF is immunosuppressive alone at high concentrations, and in combination with CsA at low concentrations. Continuous infusion of DF into the graft combined with systemic administration of CsA prolonged transplant survival in vivo. These findings suggest that high tissue levels of DF potentiate the immunosuppressive effects of CsA. PMID- 8212221 TI - Vasoactive intestinal peptide enhances lung preservation. AB - The outcome of lung transplantation is often dependent on the quality of the donor lungs. To explore a way to improve lung preservation, vasoactive intestinal peptide (VIP) was added to pneumoplegic solutions. The 4 solutions tested were Krebs solution, Krebs solution with VIP, University of Wisconsin solution, and the University of Wisconsin solution with VIP. The lungs of 8 male Sprague-Dawley rats were flushed and stored in these solutions for 24 hr. At regular intervals, tissue was sampled and examined by light, scanning, and transmission electron microscopy. Casts of the vasculature were made after 4 hr and viewed by a scanning electron microscope. Lungs appeared well preserved by light microscopy at all intervals. Although inflammatory cells around arteries, arterial constriction, bronchiolar epithelial detachment, peribronchiolar edema, and alveolar size inhomogeneity were greater with time, there was no significant difference among the 4 groups by light microscopy. Scanning microscopy of tissue at 24 hr confirmed the information found on light microscopy but did not allow separation of the groups. The vascular casts showed that edema around large vessels was less in the lungs treated with VIP (P < 0.01). Transmission electron microscopy showed that lungs stored in the solutions with VIP had significantly more normal-shaped mitochondria, less mitochondrial edema, less distortion of mitochondrial cristae, thinner basal lamina, and less aggregation of nuclear chromatin at most intervals sampled after 4 hr. We conclude that VIP added to certain pneumoplegic solutions improves the ultrastructure of rat lung stored in the cold for up to 24 hr. VIP may be an important additive to pneumoplegic solutions to improve preservation of lung before transplantation. PMID- 8212222 TI - Characterization and administration of cyclosporine liposomes as a small-particle aerosol. AB - Systemically administered CsA has not consistently suppressed the pulmonary immunoreactivity that leads to rejection in lung transplant patients. Pulmonary T cells from patients given CsA systemically still retain their immunoreactivity, which can be suppressed with added CsA. Direct application of CsA by aerosol to the respiratory epithelium should achieve high lung concentrations with minimum systemic effects. In the present study, CsA was most efficiently incorporated into liposomes composed of egg yolk phosphatidylcholine at a molar ratio of CsA to egg yolk phosphatidylcholine of 1:20. These CsA liposomes retained their biological activity and were as effective as free CsA in the suppression of anti CD3-stimulated [3H]thymidine incorporation by mouse spleen cells. The generation of a small-particle aerosol of CsA liposomes had no effect on this biological activity. CsA liposome aerosol particles have a mass median aerodynamic diameter of 2 microns, which allows for distribution of drug throughout the respiratory tract. Quantitation of CsA in the lungs and blood of mice exposed to CsA liposome aerosols for 4 days showed that as little as 15 min daily (0.11 mg/kg/day) was sufficient to achieve an estimated concentration of CsA in respiratory secretions of 6 micrograms/ml without detectable blood levels. Thus, CsA liposomes can be produced and aerosolized that achieve pulmonary concentrations with sufficient immunosuppressive activity to be effective in the treatment of lung diseases. PMID- 8212223 TI - Correction of a lysosomal deficiency by contact-mediated enzyme transfer after bone marrow transplantation. AB - The effectiveness of bone marrow transplantation for treating lysosomal deficiency diseases relies on the ability of bone marrow cells to provide the missing enzyme to various tissues of the recipient. This has been shown to occur in vitro by endocytosis of enzyme secreted by bone marrow-derived cells and also by direct cell-to-cell-contact. To investigate the mechanism of enzyme replacement therapy in vivo we have used, as enzyme donors, bone marrow cells from coat color mouse mutants that secrete very low or very high levels of a lysosomal enzyme, beta-glucuronidase. Our results show that the level of beta glucuronidase activity acquired by the tissues of recipient, enzyme-deficient mice is not related to the ability of the donor bone marrow-derived cells to secrete the missing enzyme. This finding suggests that cell-to-cell transfer of lysosomal enzymes may play an important role in the correction of lysosomal diseases by bone marrow transplantation. PMID- 8212224 TI - The role of preservation solutions in coronary endothelial damage during cold storage. AB - The effects of cold storage and type of preservation solution on coronary endothelial function are not well understood. Experiments were designed to evaluate coronary endothelial-dependent relaxation after a 4-hr cold (4 degrees C) storage in different preservation solutions. Isolated rat hearts were studied in the Langendorff apparatus for coronary endothelial function. After 30 min of stabilization, hearts were arrested with a 10-min perfusion of 4 degrees C crystalloid hyperkalemic cardioplegic solution (CHCS) containing 24 mmol/L of KCl and stored for 4 hr in the following preservation solutions: CHCS, Krebs-Ringer's solution (KR), 0.9% NaCl (NS), and University of Wisconsin solution (UW). A fifth group was perfused and stored in UW solution. Endothelial-dependent and independent coronary artery vasorelaxation were tested, respectively, by infusing 5-hydroxytryptamine (5-HT) (1 x 10(-6) mol/L) and sodium nitroprusside (SNP) (1 x 10(-5) mol/L) before and 30 min after the storage period. In hearts stored in CHCS and KR, the coronary artery flow increase to 5-HT and SNP infusion were not significantly affected. However, in hearts preserved with NS and UW solutions, 5 HT coronary response was significantly decreased, indicating endothelial dysfunction. In addition to these findings, coronary flow increase to SNP infusion was decreased in the group perfused and stored with UW, suggesting smooth muscle damage. These experiments suggest that 4-hr cold storage in NS or UW impairs endothelial-dependent coronary relaxation in the isolated rat heart model. PMID- 8212225 TI - Major histocompatibility complex-encoded ABC transporters and rat class I peptide motifs. PMID- 8212226 TI - Genetic characterization of class I genes of the RT1(1) haplotype. PMID- 8212227 TI - Studies on the RT1.E locus of the rat major histocompatibility complex. PMID- 8212228 TI - Cloning of the RT1.L gene coding for a low polymorphic class I antigen in the rat. PMID- 8212230 TI - Rapid method to determine structural polymorphism of rat major histocompatibility complex class II genes. PMID- 8212229 TI - Intracellular distribution of the major histocompatibility complex class I antigens in the rat trophoblasts. PMID- 8212231 TI - RT1-linked heat shock protein 70 genes. PMID- 8212232 TI - Rat gene map and comparative mapping with the mouse and other species. PMID- 8212233 TI - Analysis of the T-cell receptor V beta repertoire in rejecting rat cardiac allografts using a quantitative polymerase chain reaction. PMID- 8212234 TI - Analysis of the gene for the rat T-cell alloantigen RT6: evidence for alternative splicing in the 5' region. PMID- 8212235 TI - Asymmetric expression of RT6.1 and RT6.2 alloantigens in (RT6a x RT6b)F1 rats is due to a pretranslational mechanism. PMID- 8212236 TI - Demonstration of RT6 expression on a CD3- population of intestinal intraepithelial lymphocytes of athymic nude rats. PMID- 8212237 TI - Leukocyte common antigen RT7 is characterized by more than two microsatellite alleles. PMID- 8212238 TI - Xenotransplanted thyroid tumors heterogeneously express differentiation markers in nude rats. PMID- 8212239 TI - Natural killer cell alloreactivity in the rat: I. Potent in vivo recruitment of rat natural killer cells with an interleukin-2-producing cell line in intraperitoneal diffusion chambers. PMID- 8212240 TI - Natural killer cell alloreactivity in the rat: II. Predominant role of the RT1.C region in determining target cell susceptibility and specificity. PMID- 8212241 TI - Major histocompatibility complex class I expression and sensitivity to interleukin-2 activated NK cell-mediated lysis of adenovirus-transformed baby rat kidney cells. PMID- 8212242 TI - Preincubation of tumor cells with the anti-(MHC) class I antibody OX18 enhances tumor cell lysis by interleukin-2-activated NK cells. PMID- 8212243 TI - Migration patterns of rat peritoneal macrophages and dendritic cells. PMID- 8212244 TI - Cyclosporine-induced autoimmunity: critical role of autoregulation in the prevention of major histocompatibility class II-dependent autoaggression. PMID- 8212245 TI - Quantification and phenotypic characterization of the rat thymic dendritic cell population upon in vivo cyclosporine administration. PMID- 8212247 TI - Kinetics of inducer/effector cell generation in the thymus in cyclosporine induced autoimmunity. PMID- 8212246 TI - Malignant neoplasms in cyclosporine-induced autoimmunity. PMID- 8212248 TI - Model of acute graft-vs-host-disease in adult (SHR x BN.lx)F1 rats and its inhibition by adenine analog. PMID- 8212249 TI - Mercuric chloride-induced glomerulopathy in BN-rats: application to preclinical drug testing. PMID- 8212250 TI - Further study of the anti-TBM response in the spontaneously hypertensive rat using a panel of recombinant inbred strains. PMID- 8212251 TI - Background genes confer protection against homologous rat type II collagen induced arthritis in ACI (RT1a) rats. PMID- 8212252 TI - Genetic analysis of aberrant tumor necrosis factor alpha production in prediabetic BB-rats. PMID- 8212253 TI - Resistance to multiple, low dose streptozotocin-induced diabetes in rats: dependence on RT6+ T cells. PMID- 8212254 TI - Prevention of experimental autoimmune uveoretinitis by infusions of human therapeutic intravenous immunoglobulins in rats. PMID- 8212255 TI - Inhibition of experimental autoimmune diseases by MHC-binding competitor peptides: the competitor-modulator concept. PMID- 8212256 TI - Pathogenesis of xenograft reactions in rodents and other small laboratory species. PMID- 8212257 TI - Rat strain differences in complement activity correlate with hyperacute rejection of guinea pig cardiac xenografts. PMID- 8212258 TI - Allotolerance induced by intrathymic application of alloantigen: introduction of a new and clinically relevant procedure allowing heart graft survival in high responder rats. PMID- 8212259 TI - Isolation of rat migratory Langerhans cells. PMID- 8212260 TI - Conditions required for donor passenger leukocytes in the induction of tolerance by rat liver grafts. PMID- 8212261 TI - Spontaneous tolerance induced by MHC class I incompatible kidney grafts for subsequent pancreas transplants. PMID- 8212262 TI - Release of soluble MHC class I antigens before and after orthotopic liver retransplantation in the rat. PMID- 8212263 TI - Migration of cells encoded by donor-type MHC class I antigens after liver transplantation in the rat. PMID- 8212264 TI - Characterization of the anti-CD4-induced permanent acceptance of rat renal allografts. PMID- 8212266 TI - Is the allograft response to islet transplantation antigens MHC restricted? PMID- 8212265 TI - Insulin content and immunostained insulin in the pancreatic islets allografted in intrathecal space. PMID- 8212267 TI - Glomerular immune-mediated intravascular coagulation in chronic renal allograft rejection. PMID- 8212268 TI - Immunogenetic investigations of graft-versus-host reactions after small bowel transplantation with mesenteric lymphadenectomy. PMID- 8212269 TI - Differences in immunologic unresponsiveness after MHC-incompatible heart transplantation induced by donor-specific blood transfusion. PMID- 8212270 TI - Donor-soluble histocompatibility antigen selectively potentiates suppressor elements while decreasing the frequency of alloantigen-specific T cytotoxic cells. PMID- 8212271 TI - Effect of cyclosporine alone or in combination with rapamycin and brequinar on survival of hamster heart xenograft in rats. PMID- 8212273 TI - Steroid withdrawal in paediatric renal transplant patients receiving cyclosporine and azathioprine. PMID- 8212272 TI - Teniposide, doxorubicin, melphalan, cisplatin, and total body irradiation with autologous bone marrow transplantation for advanced neuroblastoma. PMID- 8212274 TI - Outcomes of rejection in adult liver transplant recipients--the Queensland experience. PMID- 8212275 TI - Donor hyaluronic acid and MEGX levels do not accurately predict posttransplant liver function. PMID- 8212276 TI - Beneficial effect of prostaglandin E1 on hepatic allograft rejection following orthotopic liver transplantation. PMID- 8212277 TI - Cyclosporine-induced interference with uptake of bile acids by human hepatocytes. PMID- 8212278 TI - Bone marrow transplantation prevents autoimmune diabetes in nonobese diabetic mice. PMID- 8212279 TI - Synergistic prolongation of renal allograft survival with cyclosporine and rapamycin. PMID- 8212280 TI - Chronic renal allograft rejection: altered distribution and reduced expression of epidermal growth factor in a rat model. PMID- 8212281 TI - Graft survival in rats following extended cold preservation was improved with recipient pretransplant cyclosporine therapy. PMID- 8212282 TI - Normoglycaemia in dogs after splenic vein reflux of autografted pancreatic microfragments. PMID- 8212283 TI - Small bowel transplantation in rats: evaluation of graft rejection using flexible fiberoscopy. PMID- 8212284 TI - Transformation of pituitary and fibroblast cell lines using human insulin c-DNA and a dexamethasone-inducible promoter. PMID- 8212285 TI - Antisense oligonucleotides decrease expression of human CD46, a regulator of complement. PMID- 8212286 TI - Effect of immunosuppression with anti-T-cell monoclonal antibodies on the survival of organ-cultured fetal pig pancreas xenografts in nonobese diabetic mice. PMID- 8212287 TI - Rejection and histopathology of renal subcapsular fetal pig pancreas xenografts in normal and anti-CD4 monoclonal antibody-treated nonobese diabetic mice. PMID- 8212288 TI - Rejection of guinea pig cardiac xenografts post-cobra venom factor therapy is associated with infiltration by mononuclear cells secreting interferon-gamma and diffuse endothelial activation. PMID- 8212289 TI - Tolerance induction with anti-CD8 monoclonal antibodies in the mouse heart transplant model. PMID- 8212290 TI - Prolonged survival of mouse cardiac allografts after CD4 or CD8 monoclonal antibody therapy is associated with selective intragraft cytokine protein expression: interleukin (IL)-4 and IL-10 but not IL-2 or interferon-gamma. PMID- 8212291 TI - Management of end-stage cardiac and pulmonary vascular disease. PMID- 8212292 TI - Metabolic effects of liver transplantation in Wilson's disease. PMID- 8212293 TI - Management of end-stage liver disease. PMID- 8212294 TI - Beneficial effect of a stable prostacyclin analogue (OP-2507) on pig livers harvested from non-heart-beating pigs. PMID- 8212295 TI - Mutagenicity of combined immunosuppressants. PMID- 8212296 TI - Use of ulinastatin for improving the viability of liver grafts. PMID- 8212297 TI - Liver transplantation during pregnancy. AB - We present a case of successful liver transplantation during the midtrimester of pregnancy, showing that pregnancy itself is not a contraindication to liver transplantation with life-threatening illness. Improvements in anaesthetic and surgical technique will enhance the possibility of foetal survival. PMID- 8212298 TI - In situ hypothermic asanguineous liver perfusion with whole blood reperfusion: a canine hepatic autotransplantation model. PMID- 8212299 TI - Effect of experimental bile duct ligation on distribution of cyclosporin A among plasma lipoproteins. PMID- 8212300 TI - Patient compliance with annual diagnostic testing after heart transplantation. PMID- 8212301 TI - Antiviral prophylaxis for CMV infection in liver transplantation. PMID- 8212302 TI - Clinical patterns and treatment of cytomegalovirus infection after solid-organ transplantation. PMID- 8212303 TI - Use of ganciclovir plus cytomegalovirus immune globulin to treat CMV pneumonia in orthotopic liver transplant recipients. The Boston Center for Liver Transplantation CMVIG-Study Group. PMID- 8212304 TI - Review of the efficacy of cytomegalovirus immune globulin in the prophylaxis of CMV disease in renal transplant recipients. PMID- 8212305 TI - Update on CMV infection in solid-organ transplantation. PMID- 8212306 TI - Monitoring for cytomegalovirus after organ transplantation: a clinical perspective. PMID- 8212307 TI - Humanized antibodies. AB - Hybridoma technology enabled rodent monoclonal antibodies to be created against human pathogens and cells, but these had limited clinical utility. Protein engineering, reviewed her by Greg Winter and William Harris, is now generating antibodies for treatment of infectious disease, autoimmune disease and cancer by 'humanizing' rodent antibodies. Humanized antibodies have improved pharmacokinetics, reduced immunogenicity and have been used to clinical advantage. PMID- 8212308 TI - The use of monoclonal antibodies to achieve immunological tolerance. AB - Monoclonal antibodies are potentially useful immunosuppressive agents. Short course of CD4/CD8 monoclonal antibody can be used to guide the immune system of experimental animals to accept organ grafts and to arrest autoimmunity. This reprogramming, reviewed by Herman Waldmann and Stephen Cobbold, is accompanied by potent T-cell dependent, 'infectious' regulatory mechanisms. A goal for therapeutic immunosuppression should be to understand and harness these innate immunoregulatory mechanisms. PMID- 8212309 TI - Immunotoxins: magic bullets or misguided missiles? AB - Thirteen years have passed since specific in vitro and in vivo killing of tumour cells by immunotoxins was first described. Why, then, has it taken so long to determine whether these drugs will have a major impact on the treatment of cancer, AIDS and autoimmune disease? The answer is that the transfer of basic discoveries to the clinic is a slow, multistep, interdisciplinary process. Thus, immunotoxin molecules must be designed and redesigned by the basic scientist depending on the efficacy and toxicity shown in vitro and in relevant experimental models. Next, each version must be evaluated by clinicians in humans through a lengthy process (1-3 years) in which the dose regimen is optimized and in which new problems and issues frequently emerge. These problems must again be modelled and studied in animals before additional clinical trials are initiated. In this article, Ellen Vitetta and colleagues discuss both basic and clinical aspects of the development of immunotoxin therapy. PMID- 8212310 TI - Modalities for reducing interleukin 1 activity in disease. AB - The therapeutic advantage of reducing the activity of interleukin 1 (IL-1) resides in preventing its deleterious biological effects without interfering with homeostasis. As such, methods attempting to block the production or activity of IL-1 have now entered clinical trials. For example, IL-1 induction of prostaglandins is one target in treating disease, and drugs preventing the production of inhibiting cyclooxygenase have well-known toxicities because they block the normal synthesis of prostaglandins in many tissues. IL-1 blockading agents, in contrast, affect only that portion of prostaglandin synthesis due to elevated IL-1, sparing the synthesis of these molecules for homeostasis. Charles Dinarello reviews the unique pharmacological advantages of manipulating IL-1. PMID- 8212311 TI - The IL-2/IL-2 receptor system: a target for rational immune intervention. AB - The expression of interleukin 2 (IL-2), induction of its multisubunit receptor and subsequent interplay of this ligand with its receptor are pivotal events in T cell activation. Our present understanding of the normal IL-2/IL-2 receptor system, and of disorders in this network in disease, opens the possibility for more specific immune intervention. Thomas Waldmann discusses how the clinical application of IL-2, agents that inhibit IL-2 synthesis and action, and anti-IL-2 receptor-directed therapy provide a novel perspective for prevention of allograft rejection and for treatment of graft-versus-host disease, select autoimmune disorders and certain neoplastic diseases. PMID- 8212312 TI - Immunostimulants. AB - Nonspecific immunostimulation has progressed from crude microbially derived substances to chemically defined drugs with selective effects on different components of the immune system. John Hadden describes how immunopharmacological analyses of structure-activity relationships, pharmacokinetics and immunopharmacodynamics have directed the effective use of these agents in disease models and suggest that they may be of value in combination with other therapies in the treatment of immunodeficiencies, cancer, infections and even autoimmune disorders. PMID- 8212313 TI - Adjuvants: current status, clinical perspectives and future prospects. AB - Adjuvants represent a key issue for vaccines currently under development. Adjuvanticity is linked to the ability to stimulate the T-cell subsets that control the major features of specific immune responses: CD4+ TH1 and TH2 cells and CD8+ cells involved in cytotoxic T-lymphocyte responses. Some well-defined immunomodulatory compounds can achieve this stimulation by inducing selective production of appropriate cytokines. Francoise Audibert and Luc Lise review the development of adjuvants and discuss how their combination with suitable vehicles should allow customization of adjuvant preparations capable of inducing protective immune responses better adapted to each type of pathogenicity. PMID- 8212314 TI - Selective immunosuppression. AB - Experimental models of autoimmune diseases have demonstrated that such disease can be prevented or treated by selectively interfering with activation of any of these cell types: antigen-presenting cells, autoreactive T cells and regulatory T cells. Luciano Adorini and colleagues discuss these approaches to selective immunosuppression and examine how similar strategies may become applicable to the treatment of human autoimmune diseases. PMID- 8212315 TI - Structure-based drug design: applications in immunopharmacology and immunosuppression. AB - Structure-based drug design (SBDD) combines the power of many scientific disciplines, such as X-ray crystallography, nuclear magnetic resonance, medicinal chemistry, molecular modeling, biology, enzymology and biochemistry, in a functional paradigm of drug development. The current strength of SBDD lies in parlaying enzyme inhibitors into drugs, but a variety of technological advances over the past few years now makes it possible to address complex biological targets, such as those regulating immunosuppression and immunoactivation. Manuel Navia and Debra Peattie discuss the SBDD paradigm and consider several of its achievements and challenges in immunopharmacology, particularly as these apply to the design of novel, potent immunosuppressants. PMID- 8212316 TI - Challenges in the therapy of HIV infection. AB - Drugs that inhibit human immunodeficiency virus (HIV) replication have been shown to have clinical utility in patients with HIV infection. However, the immunological improvement induced by available anti-HIV therapies in patients with acquired immune deficiency syndrome (AIDS) is incomplete and transient. Explanations for this may include immunological barriers to complete reconstitution, low therapeutic indices of the available drugs, and the development of viral resistance. An understanding of these processes, as discussed here by Robert Yarchoan and colleagues, may provide important leads for the development of improved therapy for AIDS. PMID- 8212317 TI - Cancer vaccines. AB - 1993 represents the 100th anniversary of William Coley's first report of tumour regressions induced by immune system activation in response to bacterial toxins. While many subsequent cancer vaccine trials have yielded tantalizing results, active immunotherapy has not yet become an established modality of cancer therapy. Drew Pardoll reviews newer molecular vaccine approaches based on rational immunological principles that have resulted in improved systemic antitumour effects in animal models. Ultimately the genetic definition of tumour specific antigens will allow the development of targeted antigen-specific vaccines for cancer therapy. PMID- 8212318 TI - Immunosuppressive therapy of autoimmune diseases. AB - Ciclosporin and cyclophosphamide show a remarkable efficacy in most autoimmune diseases. However, their effect is dependent on continuous drug administration with risks of drug toxicity and over immunosuppression. Results recently obtained in animal models, discussed here by Jean Francois Bach particularly with anti-CD3 and anti-CD4 monoclonal antibodies, indicate that reestablishment of tolerance to self antigens is a feasible goal. PMID- 8212319 TI - Donor cell chimerism permitted by immunosuppressive drugs: a new view of organ transplantation. AB - One line of thought in organ transplantation feels that immunosuppressive drugs can lead to tolerance induction by allowing a previously unrecognized common mechanism of cell migration and microchimerism to occur, persist, and in some cases, become drug independent. It has been recognized that there is a spectrum of susceptibility of different organs to cellular rejection and that the variable ability of these organs to induce donor-specific nonreactivity reflects their comparative content of migratory leukocytes. Here, Thomas Starzl and colleagues discuss how many of the enigmas of transplantation immunology can be explained by this chimerism. PMID- 8212320 TI - Investigation of vascular mechanisms: bridging the gap between basic research and clinical trials. PMID- 8212321 TI - 5-HT and antidepressants: new views from microdialysis studies. PMID- 8212322 TI - Desensitization of cell signalling mediated by phosphoinositidase C. AB - The waning of responses to cell-surface receptor activation during persistent stimulation with agonists (desensitization) is a feature common to many forms of transmembrane signalling. However, information is scarce regarding the regulatory processes that modulate the extensive group of receptors linked via phosphoinositidase C to the production of inositol 1,4,5-trisphosphate and 1,2 diacylglycerol. This situation is now beginning to change. Recent data indicate (1) that very rapid desensitization, possibly associated with receptor phosphorylation, regulates receptors linked to phosphoinositidase C, (2) that different receptors are desensitized to varying extents, (3) that receptor internalization can mediate desensitization at later times and (4) that signalling can be regulated at additional sites downstream of phosphoinositidase C. As Richard Wojcikiewicz and colleagues discuss here, these diverse regulatory events provide the means by which the breakdown of phosphoinositides and cellular responsiveness to their products are controlled during cell stimulation. PMID- 8212324 TI - [Ultracytochemical research on the different ATPases and alkaline phosphatase of the vascular plexuses of the rat brain in aging]. AB - The ultracytochemical investigation of the localization of Mg(2+)-ATPase, Na+, K(+)-ATPase (ouabain-sensitive potassium-dependent p-nitrophenylphosphatase component of Na+, K(+)-ATPase complex), Ca(2+)-ATPase and alkaline phosphatase activities in choroid plexus of the adult and old rat brain ventricles has shown the age-related decrease in intensity of the enzymatic reactions. This can influence the character of liquor production, as well as metabolic, regulatory and transport processes in the blood-liquor barrier in aging. The most typical areas of enzymes activity localization have been established, which are zones of the greatest functional significance. PMID- 8212323 TI - [Cytofluorimetric research on the epithelium of the cervix uteri in malignancy]. AB - The cervical dysplasia and cancer of the uterine cervix of 82 patients have been studied by the cyto-fluorimetric technique. There were 46 patients with dysplasia of mild, moderate and severe degree and 36 patients with different histopathologic type cancer of the uterine cervix T1-2N0M0. DNA content was determined in cytological smears and scrapings of cervix uterus epithelium using luminescent microscope equipped with photometric device FMEI-1. The mean DNA content under dysplasia of cervix uterus reliably differed from that in control (3.504 +/- 0.054 and 4.715 +/- 0.051, respectively). The level of DNA content was heterogenic and elevated in cases of intraepithelial cancer and carcinoma in situ (8.369 +/- 0.84 and 10.098 +/- 0.28, respectively). This value was considerably higher than tumor progression (9,423 +/- 0.051). PMID- 8212325 TI - [The effect of antenatal nicotine exposure on the male germ cells in Wistar rats]. AB - Chemically pure nicotine in dose 0.4, 1.5 and 5.0 mg/kg bw were percutaneously injected into Wistar rats during 1-20 (I) and 1-8 days (II) of pregnancy. The gametotoxic effect of nicotine in two-month males from offspring of the first generation (F1) was observed in disturbance of differentiation dynamics of spermatocytes at the stage of preleptotene and spermatids of the seventh developmental stage. The suggested quantitative analysis of disturbance in the behaviour of the meiotic chromosomes in metaphase I and II and anatelophase I and II has revealed that nicotine introduction in the period of isolation and migration of the primary sex cells into embryo gonads (2nd series) induces an increase in the level of pathological maturation divisions in the male offspring. PMID- 8212326 TI - [The effect of hyperbaric oxygenation on H3-thymidine incorporation into human fibroblast cells with different ploidies]. AB - The effect of different regimens of hyperbaric oxygenation (0.2 MPa and 0.4 MPa for 1 or 3 hour) has been investigated in the culture of diploid and triploid human fibroblasts, picked out from aborts. The quantity of marked thymidine in nuclei of cells depends on both the value of pressure and time of treatment. HBO causes stimulant effect under 3-hour treatment. Influence of different regimens of HBO on human fibroblasts reveals high resistance of triploid to oxidative stress in comparison with diploid fibroblasts. PMID- 8212327 TI - [The role of the sympathetic-hypothalamo-hypophyseal-adrenocortical system in altering the morphofunctional properties of the lysosomal apparatus of neutrophilic leukocytes under conditions of immobilization stress]. AB - The investigations were carried out on rabbits. The morphofunctional properties of lysosomal apparatus of neutrophilic leukocytes under the conditions of beta adrenoreceptor and the suppression of the hypothalamic-hypophyseal-adrenocortical system (HHAS) reactivity as the result of immobilization stress have been studied. It has been noted that sympathetic nervous system and HHAS take part in the regulation activity of the lysosomal apparatus of neutrophil leukocytes. PMID- 8212328 TI - [A population genetics analysis of the structure of hybrid populations of Rana esculenta L. complex (Amphibia, Ranidae)]. AB - Population-genetic analysis conducted in hybrid populations of Rana esculenta complex from neighbourhood of Kiev has shown a high portion of recombinant frogs within Rana esculenta specimens and limitation of gene flows from one species to the other. The mechanisms of limitations are connected with assortative crossings within R. ridibunda and R. lessonae and low viability of frogs with a recombined genotype. PMID- 8212329 TI - [The distribution of deletions in the dystrophin gene in patients with Duchenne muscular dystrophy in Ukraine]. AB - DNA analysis of deletions within 14 exons and promoter region of dystrophin gene was performed in 34 Ukrainian families with high risk of muscular Duchenne dystrophy. The presence of dystrophin gene deletions in different exons was found clustering near central part of dystrophin gene. The necessity of DNA analysis of mutations in dystrophin gene and its use for screening and prenatal diagnosis of muscular Duchenne dystrophy is under discussion. PMID- 8212330 TI - [Digitalis blood determination: why and when?]. PMID- 8212331 TI - [Biological diagnosis of recurrent human hydatidosis]. PMID- 8212332 TI - [Gastritis, ulcerous syndrome without ulcer and Helicobacter pylori (250 cases)]. PMID- 8212333 TI - [Cancer of the gastric stump in 7 cases]. PMID- 8212334 TI - [The value of research on specific IgA and IgM antibodies in chlamydia trachomatis infections in adults]. PMID- 8212335 TI - [Clinical evaluation of methoxy-isobutyl-isonitrile in the diagnosis and localization of myocardial infarction]. PMID- 8212336 TI - [Human listeriosis: 2 new cases in Tunisia and literature review]. PMID- 8212337 TI - [Atypical vertebral tuberculosis: value of tomodensitometry. 2 case reports]. PMID- 8212338 TI - [Prune Belly syndrome: a new case report]. PMID- 8212339 TI - [Renal anthrax: a case report in a child]. PMID- 8212340 TI - [Role of human genetics in medical pathology]. PMID- 8212341 TI - [New tarsotomy technique in the treatment of post trachomatous trichiasis: 3000 case reports]. PMID- 8212342 TI - [Cardiac insufficiency in the young child: 82 cases]. PMID- 8212343 TI - [Seasonal variations in chronic juvenile arthritis]. PMID- 8212344 TI - [The Tunisian diabetic adolescent]. PMID- 8212345 TI - [Etiologic factors in primary bronchial carcinoma in Tunisia]. PMID- 8212346 TI - [Scorpion bites in the district of Sidi Bouzid: epidemiological study and organization of control]. PMID- 8212347 TI - [Ultra-sensitive TSH test using TRH in anterior hypophyseal insufficiency]. PMID- 8212348 TI - [Krukenberg's tumour: a case report]. PMID- 8212349 TI - [A rare case of abdominal pregnancy: lithopedion]. PMID- 8212350 TI - [Ovum transplantation in public and private practice]. PMID- 8212351 TI - [Fertilization in vitro. A review over the medical indications and suggestion to unified guidelines for public fertility clinics in Denmark]. AB - Medical indications for in vitro fertilization and embryo transfer (IVF-ET) internationally and in Denmark are reviewed. Reports from large international centres document that tubal infertility, unexplained infertility, endometriosis and male infertility are equally good indications for IVF. Traditionally, tubal infertility has been the only medical indication qualifying for IVF treatment within the National Health Service in Denmark. Thus, in this country, couples with unexplained and male infertility and with endometriosis have to pay up to 25,000 D.Kr. per IVF-ET treatment in private fertility clinics. Since there is no scientific basis for this discrimination, it is urged that the present rules are changed, so that couples with unexplained and male infertility and endometriosis are also allowed IVF treatment free of charge in the public fertility clinics. PMID- 8212352 TI - [Ovum donation. A review of and a suggestion to unified guidelines for treatment at public fertility clinics in Denmark]. AB - The most common indication for oocyte donation is ovarian insufficiency due to premature menopause or resistant ovarian syndrome and ovarian dysgenesis with either normal or abnormal (e.g. Turner's syndrome) karyotype. In Denmark, oocyte donation must be anonymous, and the donors have to be other infertile patients undergoing in vitro fertilisation (IVF), treatment. It is suggested, that the National Health Service offers oocyte donation to hypergonadotropic women with ovarian insufficiency, as well as to a few other groups who fulfil the criteria for IVF treatment, but where this treatment cannot be completed. Oocyte donors must be less than 35 years old, physically and mentally healthy and without major genetic diseases in the family. The donor must be screened for HIV, hepatitis, syphilis, chlamydia and gonorrhoea. We propose that those patients who have more than six oocytes aspirated, allowing "surplus" oocytes to be donated. It is also proposed that the departmental order from the Ministry of Health be changed, so that normally fertile women are allowed to donate oocytes. Oocyte donation should be reported to a central authority. PMID- 8212353 TI - [Freezing of human embryos. A review of and a suggestion to unified guidelines for treatment at public fertility clinics in Denmark]. AB - In Denmark, legislation has made cryopreservation of human oocytes and embryos possible since October 1992. The legislation is reviewed. Cryopreservation of embryos constitutes a significant improvement of infertility treatment. The number of oocyte pick-ups and the number of embryos transferred can be reduced without compromising the total likelihood of success of in-vitro fertilization (IVF) treatment. According to Danish law, frozen embryos can only be stored for one year. This limit will interfere with patient expectations in numerous cases, and the time limit should be expanded. Moreover, freezing of embryos should be allowed in connection with oocyte donation programmes. PMID- 8212354 TI - [Freezing of human embryos: the first Danish results]. AB - The first human pregnancies reported in Denmark following in vitro fertilization and embryo transfer of frozen and thawn embryos are presented. A total of nine embryo transfers, with a mean of one point eight embryos per transfer, were carried out, resulting in three singleton pregnancies. The benefits for the infertile couple, the ethics and technical aspects are discussed with respect to Danish legislation. PMID- 8212355 TI - [Information on parity in the medical registry of births of the National Board of Health. Validation with the help of a new fertility database in Danish Statistics]. AB - Information on parity from the Medical Register of Births kept by The Danish National Board of Health was compared with a parity value calculated with the aid of a new, individual-based Fertility Database compiled by the Danmarks Statistik. The parity information contained in the Medical Register of Births is recorded by the midwife at each birth, where the woman's number of previous live-births is noted. The Register on Population Statistics records live-born infants with reference to their mother, and parity is calculated in the Fertility Database on the basis of these records. The results show a very high degree of accordance between the two measures of parity. More than 99.5% of women with parity one who have given birth since 1978 are classified as such by both systems. Due to an ambiguity in the midwife's birth notification form there has previously been uncertainty regarding the classification of first-time mothers based on the information contained in the Medical Register of Births. This evaluation shows that this information can be regarded as valid. PMID- 8212356 TI - [Decline in semen quality from 1930 to 1991]. AB - It has been suspected for years that semen quality has declined. However, the issue is still controversial since previous studies were criticized for methodological errors. We therefore attempted to systematically review the complete international literature on semen quality since 1930 with rigorous selection criteria and statistical analysis. Based on a literature search using Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-august 1991), we identified 61 papers concerning sperm density in a total of 14,957 males without a history of infertility. A significant decline in mean sperm density from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in mean seminal volume from 3.40 ml to 2.75 ml (p = 0.027) was noted. The incidence of testis cancer and possibly also that of cryptorchidism and hypospadias has increased during the same relatively short time period. Such a remarkable deterioration in male genitourinary function is more likely to be due to environmental rather than genetic factors. PMID- 8212357 TI - [Is the new chaos- and fractal research of importance to medical science?]. AB - Living systems are characterized by a complexity of structure and function which goes well beyond the descriptive capacity of classical physical and mathematical methods. During the latest decade, the development of non-linear dynamics has introduced a series of new concepts and tools to describe even extremely complex systems. This has led to a better understanding of the processes through which complex structures can arise from very simple interactions. The present and a following paper will give a brief introduction to some concepts and methods of this new science. PMID- 8212358 TI - [Enchondroma of the scaphoid complicated by fracture]. AB - A thirteen-year old boy fell on his outstretched left palm, resulting in hyperextension. X-rays showed a fracture of the scaphoid through a cystic appearance in the center of the scaphoid. For two years, the patient was treated conservatively without any sign of healing. After operation, where curettage and autogenous-bone grafting were performed, the scaphoid healed completely. Biopsy revealed enchondroma. PMID- 8212359 TI - [Reproductive health--genetic or social heritage]. PMID- 8212360 TI - [Prognosis for children with birth weight under 1,500 gram]. PMID- 8212361 TI - [A stethoscope can also be an excellent hearing aid]. PMID- 8212362 TI - [Treatment during remission of hypertension? A new goal in antihypertensive treatment]. PMID- 8212363 TI - [Withdrawal of antihypertensive treatment]. AB - Research over the years has given considerable evidence that medically induced normalization of the blood pressure in hypertensive patients decreases cardiac and cerebrovascular morbidity. On the other hand, few studies have attempted to evaluate the consequences of a subsequent withdrawal of anti-hypertensive treatment. This paper assesses the research in this field and concludes that approximately 20-25% of patients with mild hypertension remain normotensive during a follow-up period of 1-2 years. Based on this conclusion, the following is recommended: in patients with well treated, mild hypertension, who have been normotensive for a minimum of two years, withdrawal of antihypertensive treatment could be attempted followed by monthly measurements of blood pressure. Concurrent non-pharmacological intervention is recommended. Sequential antihypertensive therapy may thus be an alternative to the currently established strategy of life long treatment. PMID- 8212364 TI - [Long-term treatment with octreotide of patients with acromegaly]. AB - We bring our experiences with and results of octreotide treatment for 0.5 to seven years in 26 highly selected acromegalic patients, i.e. they had almost all been operated upon before or were for other reasons not first-choice neurosurgical candidates. Sixteen patients responded immediately to octreotide and achieved good control of symptoms and average serum growth hormone levels below 5 micrograms/l. Five additional patients responded adequately to octreotide after a renewed neurosurgical attempt, and two other patients achieved satisfactory control after successful neurosurgery. Thus we had to resort to radiation therapy in three out of these 26 patients. We should like to emphasize the fact that acromegalic patients, who initially do not respond adequately to octreotide therapy, may often do so after a renewed partial adenomectomy. Octreotide therapy has in our hands been practically without side effects, apart from gastrointestinal symptoms during the initial days of treatment. All 26 patients had an ultrasound-scan of the gallbladder and biliary tracts before and during long-term octreotide administration, and with the exception of one patient with gallbladder sediment, in whom no pretreatment scanning had been performed, we had no development of biliary tract abnormalities in these up to 65 year old patients. This may be due to composition and timing of meal intake in relation to that of octreotide. Fecal fat excretion, D-vitamin metabolites in serum and prothrombin time were similar in octreotide-treated and untreated acromegalic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212365 TI - [Is there to be a renaissance of surgical treatment of ulcers?]. AB - Medical treatment of peptic ulcer disease with H2-blockers has over the last ten years practically replaced surgical treatment of this condition, due to greater patient compliance, high effectivity and negligible side-effects. The treatment is, however, strained by the relatively high cost of medication. Development of techniques for laparoscopic vagotomy, which is associated with a considerably reduced postoperative morbidity and reconvalescence as well as entailing only one to two days hospitalization and a minimal surgical scar, has re-opened the debate on medical versus surgical treatment of ulcers. On the basis of a literature review of risk of ulcer recurrence, risk of ulcer complications, cost and compliance associated with the two types of treatment, it is concluded that surgical treatment of peptic ulcers by laparoscopic parietal cell vagotomy should have a renaissance as regards the treatment of patients, who have frequent recurrences when maintained on ordinary medical treatment. However, the development of new, alternative principles for the cheap, effective and complication-free medical treatment of these patients, for example via elimination of helicobacter pylori infection, will necessitate a re-evaluation as regards the treatment of choice. PMID- 8212366 TI - [Laparoscopic parietal cell vagotomy. Preliminary results]. AB - The results from 11 laparoscopic parietal cell vagotomies are presented. The procedure could be carried out in all patients. The median day of discharge after the procedure was day 1 (range 1-16), median convalescence time 7 (range 4-50) days. One patient required re-operation due to a perforation at the lesser curvature. This complication is ascribed to the learning phase. If a sufficient reduction in gastric acid secretion can be documented in a larger series of patients, laparoscopic parietal cell vagotomy should be considered a serious alternative to conservative treatment. PMID- 8212367 TI - [Ambulatory labor--experience from the first 2 years]. AB - A trial arrangement for mandatory early discharge for all normal multiparae in 1990 and 1991 was evaluated. 63.4 percent of 1661 multiparous women were discharged within 24 hours of giving birth. During the period the mean time to discharge rose from 6 1/2 to 10 1/2 hours. Only 2.6 per cent of the children were readmitted to hospital, as were 1.2 percent of the mothers. The purpose of the trial was to save money, but in the trial period no money was saved from the early discharged women, the savings came from deductions in the perinatal service to the non-early discharged women. PMID- 8212368 TI - [Duration of breast feeding after mandatory early discharge]. AB - A trial arrangement for mandatory early discharge for all normal multiparae was started in 1990 and the duration of breastfeeding was investigated by a questionnaire. 89 mothers who stayed at the hospital were compared to 113 mothers who were discharged within 24 hours after delivery. The latter group was also compared to 122 early discharged mothers who delivered 14-17 months after the trial arrangement had started. The three groups were comparable in all aspects. After four weeks a large proportion of the later discharged mothers were still breastfeeding compared to the other two groups (p < 0.001). This difference disappeared later, hence when comparing the total duration of breastfeeding no differences were found between the three groups. PMID- 8212370 TI - [Surgical treatment of hypertrophic obstructive cardiomyopathy. A retrospective study]. AB - Twelve patients, three male and nine female, suffering from hypertrophic obstructive cardiomyopathy were operated during the period 1976 to 1991. Operative methods were myotomy-myectomy (Morrow-procedure), mitral valve implantation or both. During the perioperative period two patients developed conduction disturbances requiring pacemaker implantation, five patients had left bundle branch block, and one died. The NYHA class was significantly reduced postoperatively (p = 0.0002). Five of eleven patients surviving the perioperative period died postoperatively after a mean follow-up of 6.3 years. It is the authors' opinion, that operation should be considered in patients suffering from hypertrophic obstructive cardiomyopathy, who have a left ventricle outflow gradient of 50 mmHg or more, and who despite medical treatment have symptoms placing them in NYHA class III-IV. PMID- 8212369 TI - [Severe obstructive lung disease. The effect of the calcium antagonist isradipine on working capacity, pulmonary function, morbidity and survival]. AB - Several studies have reported beneficial haemodynamic effects of calcium antagonists in the treatment of patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension. Such effects include a decrease in pulmonary vascular resistance, an increase in cardiac output, and an increase in oxygen delivery, but the clinical implications of these effects remain uncertain. We therefore designed this first randomized, double-blind, placebo-controlled, long-term study to investigate the clinical effects of a calcium antagonist (isradipine) on patients with COPD. The aim of the study was to investigate the hypotheses that isradipine was able to increase working capacity and lung function, and decrease morbidity and mortality. During a 22-month observation of 52 patients with severe COPD no statistically significant differences between the isradipine group and the placebo group were found with regard to these parameters. It is concluded that the existing evidence does not justify the introduction of calcium antagonists as part of the routine treatment of COPD with pulmonary hypertension. PMID- 8212371 TI - [Cataract surgery using phacoemulsification]. AB - Clinical results are reported in a consecutive series of 111 patients undergoing cataract surgery by phacoemulsification. On the first day after surgery, 69% of all cases had a visual acuity of 20/40 or better without any spectacle correction. Four months later this percentage had increased to 79%. Compared with a series of patients, operated by conventional extracapsular extraction, the corneal astigmatism was found to be significantly reduced in the phacoemulsification series (p < 0.001). The decrease in surgically induced astigmatism together with tailoring of the power of the intraocular lens (IOL) accounted for the good unaided visual acuity in the phacoemulsification group. Phacoemulsification is concluded to offer good optical control of the postoperative refraction in cataract patients. PMID- 8212373 TI - [Papillary transitional cell carcinoma of the bladder after 1 year use of a double-J ureteral catheter]. AB - A 37-year old man with a five-year history of nephrolithiasis was catheterized with a double-J ureteral stent (Angiomed) in the left ureter before extra corporeal shock wave lithotripsy. After eight lithotripsy treatments over the course of one year, the double-J stent was removed. Papillary tumor was discovered around the left ureter ostium. Histology showed papillary transitional cell carcinoma grade 2 without invasive growth. No neoplasm has previously been observed after using double pigtail stents for longtime-stenting. One should keep this case in mind, when controlling ureteral stents that are left in place for longer periods. PMID- 8212372 TI - [Changes of sexual behavior among Danish homo/bisexual men under the impact of HIV/AIDS epidemic]. AB - In October 1991, 1.567 gay/bisexual men throughout Denmark returned an anonymous questionnaire enclosed in the magazine of the National Gay and Lesbian Association. Most were younger, well educated men living in the Copenhagen area. 76% had been tested for HIV, 15% were infected. As in 1988, the median number of partners in 1991 was 2-5. Eighty-two percent of the sexually active men engaged in anal sex, of these half used condoms consistently. Anal sex was practised more with steady partners and condom use was more common with casual partners. One out of eight had engaged in unprotected anal intercourse with a partner with discordant HIV-serostatus, down from one in three in 1988. It is concluded, that Danish gay men have not further limited their sexual life during the later years. The majority of the respondents have increased sexual safety, but risky sex still prevails among a substantial minority, and safe sex campaigns should continue. PMID- 8212374 TI - [Endothelial cyst in the adrenal gland]. AB - Suprarenal cysts are rare. A case of a 3.5 l cyst incidentally discovered in a 30 year old woman is described. Operative treatment is recommended in order to avoid spontaneous rupture and to exclude malignancy. Endothelial origin can be established by a specific immunohistochemical staining, factor VIII antibody. PMID- 8212375 TI - [Lupus nephritis]. PMID- 8212376 TI - [Psychosocial conditions and intervention in cancer patients]. PMID- 8212377 TI - [Localized nodular myositis--a focal form of myositis]. PMID- 8212378 TI - [Lighter gas and toy balloons]. PMID- 8212379 TI - [The Salmonella epidemic in Denmark]. PMID- 8212380 TI - [Infection with multi-resistant Salmonella virchow acquired in Denmark]. AB - Two cases of infection with multiply resistant Salmonella virchow were probably acquired in Denmark. A 30-year old man and a 20-year old woman had both eaten from the same buffet at a summer restaurant and developed gastrointestinal symptoms and fever after three and six days, respectively. The patients ran a fever for two and five weeks before the admission to the hospital and the woman developed a tuboovarial abscess complicated by peritonitis. S. virchow resistant to ampicillin, streptomycin, tetracycline, and sulfonamide was isolated from faeces in the male patient and from intraabdominal pus in the female patient. Among 35 Danish S. virchow isolates from January 1 to August 31, 1992 there was only one additional multiply resistant isolate (resistant to streptomycin, tetracycline, sulfonamide, and chloramphenicol) the source of which was unknown. PMID- 8212381 TI - [Cytomegalovirus infection. A review]. AB - Once considered to be an infrequent cause of human disease, human cytomegalovirus (CMV) is now recognized as being one of the most common congenital infections leading to birth defects, and furthermore, it is a common opportunistic infection associated with serious illness and death in immunocompromised patients. CMV has been assigned to the herpes family of viruses. It is an enveloped DNA virus. About 50%-60% of Danish blood donors have anti-CMV. This figure is dependent on age, race, socioeconomic status, sexual behaviour and geographical area. Patients exhibiting symptoms and signs of primary or reactivated CMV infection should be further evaluated with appropriate laboratory tests, as treatment of CMV disease with antiviral chemotherapy such as ganciclovir or foscarnet, has proven to be effective. PMID- 8212382 TI - [Recruitment of patients for clinical trials on psoriasis. A review of recent dermatological literature]. AB - Reports of 62 psoriasis clinical trials listed in the Cumulated Index Medicus during 1988 and 1989, and published only in leading dermatological journals, were evaluated with respect to different elements of research methodology concerned with the recruitment of patients. The evaluation included items such as eligibility criteria, the sampling process, ethical considerations, and sample size calculation. Major weaknesses in the description of all aspects of the recruitment procedure were demonstrated. For example, a quantitative disease activity criterion at entry was mentioned in 15% of the studies, consecutive patients were included in 5% of the trials, approval from an ethics committee and informed consent of patients was mentioned in 16% of the studies and a pre-study sample size calculation was not mentioned in any of the trials. PMID- 8212383 TI - [Psoriasis and cancer]. AB - This study reports the cancer incidence among 6910 individuals in Denmark discharged from hospital over the period 1977-1987 with a diagnosis of psoriasis. Patients were identified in the National Hospital Discharge Register and information on cases of cancer was obtained through the files of the Danish Cancer Registry. A 2,5-fold increased risk was observed for nonmelanoma skin cancer in men and women, with no preponderance of any specific histologic subtype of cancer. The incidence of non-cutaneous cancers at all sites combined was significantly increased in the study group, owing mainly to excesses of lung cancer in men (relative risk (RR) = 1.4) and women (RR = 1.6), of cancer of the larynx and pharynx in men (RR = 2.8 and 3.9), and of colon and kidney cancer in women (RR = 1.6 and 2.3). The effect of cigarette smoking on the risk for non cutaneous cancer could not be assessed in this study; however, antipsoriatic treatment such as ionizing radiation and oral arsenicals must be considered as a possible cause, particularly in relation to colon cancer which has been observed in excess in two other studies of psoriatic patients, but also in relation to kidney and lung cancer. PMID- 8212384 TI - [Semiautomatic defibrillation in out-of-hospital cardiac arrest]. AB - In a Danish suburban community the following attempts were made aimed at increasing survival of out-of-hospital cardiac arrest (CA): the citizens were offered training in diagnosis and treatment of CA and the ambulances serving the community were provided with a semiautomatic defibrillator. The results of these effects were evaluated over a two-year period. One hundred and seventy persons out of a population of 85,824 received training in CPR. The study included 113 cases of CA due to ischaemic heart disease. CA was witnessed in 84 cases (74%). Bystander CPR was attempted in 21 cases out of whom three survived (14%), compared to seven survivors among the remaining 92 patients (8%). If CPR was initiated within five minutes of CA, eight of 57 patients survived (15%), compared to one in 31 cases if resuscitation was attempted later. If ventricular fibrillation was present seven of 51 patients survived (14%); none of the 24 patients who initially had asystole, survived. In 336 situations tape recordings of the ECG at CA were available for analysis. Ventricular fibrillation was present in all of the 129 cases where DC-conversion was advised by the apparatus. There were two additional cases, one of ventricular fibrillation of low frequency and one of ventricular tachycardia where DC-conversion was not advised, but might have been beneficial. PMID- 8212385 TI - [Treatment of accidents occurring in a municipality in general practice and emergency clinics]. AB - In one Danish municipality inhabited by 9433 persons, 9119 were registered in the health security system as group 1-secured (i.e. full public health coverage). Fifteen general practitioners in seven practices participated in a one year project by registering accidents where the general practitioner was the primary treatment contact. These general practitioners were allocated 84.5% of the group 1-secured persons in the municipality. The general practitioners were the primary contact persons in 466 accidents. The one year contact incidence rate was 61 per 1000 secured persons. During the same period the total number of inhabitants of the municipality made 1006 contacts to the local emergency rooms as a direct consequence of accidents. The one year rate of contact incidence for emergency rooms was 107 per 1000 inhabitants. The total rate of contact incidences to medical practitioners in the local health system is calculated to be 166 per 1000 inhabitants. The general practitioners saw more children and more accidents that had taken place in schools and day care-centres. Injuries caused by acute muscular overtraining led more frequently to contact with general practice. Fewer fractures and open wounds due to accidents were registered in general practice than in the emergency room. During the daytime working hours, the general practitioner was contacted more frequently than the emergency room. PMID- 8212386 TI - [Distal femoral fractures treated by external fixation with Orthofix]. AB - In the period from November 1987 to March 1990 17 supracondylar femoral fractures were treated a.m. Orthofix at the orthopaedic departments in Roskilde and Koge, Denmark. The fractures were classified according to Muller et al. There were 13 in group 2A and four in group 3A. In 16 cases the fractures occurred after minimal trauma. Time of operation was 55 minutes (30-150). The patients were fully mobilized after 16 days. The dynamizising procedure took place after six weeks, and the fixator was removed when the fracture was healed after 11 weeks. According to Neer's scoring system the results were good or excellent in 12 cases, and fair on one case. In all patients we found solid bony union. In seven cases we found pin infection. It was not necessary to operate because of the infection in any of these cases. Four cases were complicated with dislocation of the fracture because of bad locking at the ball joint of the fixator. We find this method easy to use in contrast to traditional osteosynthesis. The patients are quickly mobilized. It is easy to correct the fracture and the method gives solid bony healing. PMID- 8212387 TI - [Bacteriological urine analysis as part of check-ups on children. A retrospective study from general practice]. AB - This paper presents a retrospective study of asymptomatic bacteriuria from general practice. The general practitioner had screened children's urine specimens for asymptomatic bacteriuria at the eight regular health examinations during preschool age. The urine was collected in special adhesive bags or as a midstream clean catch and investigated by stix and culture at the practitioner's. When significant bacteriuria was noted, a new urine sample was collected for analysis. If asymptomatic bacteriuria was again noted, the culture plates were sent to a microbiological hospital department for determination of bacterial type and antibiotic resistance. The children were subsequently treated with a relevant antibiotic. The material collected during 12 years consisted of 658 urine samples obtained from 1295 examinations of 208 children. Thirty-five samples (5.3%) were positive, and 30 of the children presented at least one positive sample (14.2%). Most of the positive samples were obtained during the first two years. However, the material is too small to obtain statistically positive results and must due to its retrospective nature be interpreted with care. Nevertheless, the high rate of infection in our study motivates the initiation of a regular prospective study. PMID- 8212388 TI - [Continuing clinical education in adult psychiatry is not sufficient--a questionnaire study on training and participation]. AB - In June 1990 the Section of Younger Psychiatrists affiliated to the Danish Psychiatric Society conducted a survey among junior doctors (JD) regarding clinical and theoretical training during attachments to psychiatric departments. The aim was to evaluate clinical and theoretical training and compare the results with the goals given by the Danish Psychiatric Society. Sixty-two percent (n = 362) answered a questionnaire including personal data, classification of the department, and participation in the organized training and supervision in the psychiatric departments. The introduction to the department at appointment was insufficient for 97% of the JDs. Fifty percent had been offered and 24% had participated in the advised number of clinical conferences. Sixty-nine percent had been offered and 13% had attended the theoretical conferences, while 43% respectively 41% had been offered and had attended the theoretical sessions. Two thirds of the JDs participated in 50% or more of the organized training. Reasons for not attending were day-offs and pressing duties in the department. The results are discussed in relation to ongoing changes of the educational structure and of doctors appointments in the departments. PMID- 8212389 TI - [Air cysts in the small intestine]. AB - Pneumacystoides intestinalis (PCI) is a rare disease consisting of gaseous cysts localized in the wall of the gut. PCI is described from stomach to rectum, but is most frequently associated with chronic obstructive lung disease (COLD), peptic ulcers or other lesions in the gut. Idiopathic PCI is also reported. In this report, the radiological appearance of PCI in the small intestine of a 15 year old male patient with low mechanical obstruction of the small intestine is shown to be difficult to distinguish from the radiological findings under gangrenous conditions in the intestine, where gas assembles in the gut wall. It is suggested that PCI might be considered, when gas is demonstrated in the intestinal wall on routine x-ray of the abdomen, in the absence of accompanying clinical signs of intestinal necrosis. PMID- 8212390 TI - [Systemic strongyloidiasis. Hyperinfection syndrome and disseminated strongyloidiasis]. AB - Hyperinfection syndrome and disseminated strongyloidiasis are serious complications to the rather harmless upper bowel infection with Strongyloides stercoralis. The infection is endemic in tropical and subtropical climates as well as in many parts of Eastern Europe. Systemic strongyloidiasis occurs mainly in immunosuppressed patients, but apparently not in HIV-patients. The condition has a significant mortality. Early diagnosis and sufficient treatment is essential to reduce the mortality. The treatment is thiabendazole or albendazole. With increased travel and immigration the infection and its complications can also be seen in non-endemic areas. A case report is presented to heighten awareness of this serious condition, which is preventable. PMID- 8212391 TI - [Tendovaginitis stenosans. Also an occupational disease]. PMID- 8212392 TI - [An orientation from the drug department of the Board of Health Care and Welfare and the Scientific Ethical Committee system]. PMID- 8212393 TI - [Quality assurance in general practice]. PMID- 8212394 TI - [Premature infants]. PMID- 8212395 TI - [Cervical dysplasia--is the treatment optimal?]. PMID- 8212396 TI - [Cryotherapy of cervical intraepithelial neoplasia. Long-term prognosis]. AB - Cryotherapy for the treatment of cervical intraepithelial neoplasia (CIN) was performed in 261 patients and the patients were followed for five to 10 years. Cure rate fed significantly with inoeasing grade of CIN and with endocervical involvement. In pure exocervical lesions, 91% and 77.8% of patients with respectively CIN II and CIN III were cured. In patients with endocervical involvement, the grade of lesion was not significant. Life-table calculations showed an over-all risk of persisting CIN during the first year of observation of 8.8%, and a risk of 0.8% during years 6 to 10. Patients age was of no significance. Endocervical involvement should be a contraindication to cryotherapy, and a careful follow-up schedule is mandatory. A careful colposcopic examination especially concerning the lesion area might help to increase the cure rate in patients with exocervical CIN III lesions. PMID- 8212397 TI - [Expectoration--an underestimated symptom?]. AB - The prognostic value of pulmonary mucus hypersecretion is reviewed and is found to be considerable as regards COPD-mortality, -morbidity, and respiratory cancer. In contrast to previous belief, mucus hypersecretion cannot be considered a "harmless" respiratory symptom. The most efficacious intervention seems to be cessation of smoking, whereas little evidence is available supporting the benefit of long-term medical treatment or treatment involving chest physiotherapy. PMID- 8212398 TI - [Bupivacaine in spinal anesthesia. The spread of analgesia--dependence on baricity, positioning, dosage, technique of injection and patient characteristics]. AB - The spread of sensory blockade during spinal analgesia using bupivacaine is influenced by a number of factors concerning baricity, positioning, dosage, technique of injection and patient characteristics. The glucose-free 0.5% solution acts as a hypobaric solution. The interaction of baricity and posture during and immediately after the injection of this solution is of utmost importance. However, the level of analgesia when using hyperbaric solutions seems not to be affected by posture. The dose of bupivacaine is also of great importance, independent of the type of solution used. Of modest importance is patient age, irrespective of baricity, while obesity and injection level only matter when the glucose-free solution is used. Injection speed seems of modest importance, while barbotage and direction of the needle have no or minimal clinical importance. The problem of unpredictability of the sensory blockade, a major one in spinal analgesia, is yet to be solved. PMID- 8212399 TI - [Recklinghausen neurofibromatosis in children]. AB - Neurofibromatosis Recklinghausen (NF-1) is a progressive disease, which is inherited as a monogenic, autosomal dominant trait. The NF-1 gene is localized on chromosome 17(17q11.2), allowing antenatal and postnatal diagnostic tests. The prevalence of NF-1 is 1/5000, but the disease may be more prevalent in children and young adults below twenty years of age. The pathophysiological mechanisms are presently unknown, although the gene defect can result in experimental inhibition of tumor suppression. NF-1 in childhood can be associated with a variety of clinical and psycho-social problems, and the diagnostic criteria may not be met at birth. More than six cafe-au-lait spots in individuals should give rise to suspicion, and axillary and inguinal freckels are considered to be pathognomonic for the disease. Neurofibromas are found in 15% of children below six years of age with NF-1. Sphenoidal dysplasia is pathognomonic (but very rare) in children with NF-1, and pseudoarthrosis of the tibia is seen in three percent of cases. Scoliosis is prevalent, and back deformities are found in 60% of all patients. Malignancies are more prevalent in patients with NF-1, and in children opticus glioma and nonlymphocytic leukaemia are the most frequent. In addition, learning difficulties are found. The treatment and clinical control of children with NF-1 is a specialist task, which requires a centrally coordinated function. This organization has not yet been established in Denmark. PMID- 8212400 TI - [Ethical problems of the emergency room work]. AB - We studied the incidence of ethical problems occurring in the emergency room of a large Danish provincial hospital. During a period of two months, 3620 unselected patients were treated, and in 190 (5.2%) of these cases the attending physician identified one or more ethical problems. The three most common problems identified were a. potentially suboptimal treatment due to communication difficulties, b. potentially suboptimal treatment due to a high work-load in the emergency room, and c. questions raised by patients who presented with minimal lesions not requiring any treatment. It is suggested that a reduction of the number of ethical problems encountered in the emergency room can be obtained by allocation of more resources, education of the staff, and education of the general public explaining the role of the emergency room. PMID- 8212401 TI - [In situ bypass and diabetes]. AB - From 1986 through to 1990 a total of 483 in situ bypass procedures were performed in 444 patients. Preoperative risk-factors were equally distributed among diabetic (DM) and non-diabetic (NDM) patients, except for smoking habits (DM:48%, NDM:64%, p = 0.002) and cardiac disease (DM:45%, NDM:29%, p = 0.005). Critical limb-ischaemia was more often present in diabetic than non-diabetic patients (DM:57%, NDM:36%, p = 0.0002). Diabetic patients had a significantly lower distal anastomosis than non-diabetic patients (p = 0.00001). There were no differences among diabetic and non-diabetic patients regarding three years primary and secondary patency (58% and 64% respectively), and regarding major amputations. However, the rate of minor amputations was higher in insulin-dependent compared with non-insulin-dependent diabetics, who in turn had a higher rate than non diabetics (p < 0.00001). A markedly decreased survival rate was found in diabetics (p < 0.00005). We found the in situ bypass technique very useful in the treatment of critical ischaemia of the lower limb in diabetic patients. The overall results in diabetic patients, whether insulin-dependent or not, were equal to those in non-diabetic patients. PMID- 8212402 TI - [Chronic pain after spinal cord injury--a descriptive study]. AB - Sixty-three patients with chronic pain following spinal cord injury (SCI) completed a questionnaire about different aspects of pain. Median duration from SCI to first experience of pain was four months. The duration of pain was for a median of three years. Fifty-six percent graded their pain as strong or unbearable. Ninety-two percent of the patients had daily pain, and in 43% the pain was constant day and night. The pain seriously affected daily living in 38% and sleep was disturbed in 48%. The pain had worsened in 43% and improved in 16% since its start. No association was found between performed spinal surgical procedures and the intensity of pain, the course of the pain, the time from SCI till pain started or the size of the area of pain. The most frequently used words to describe pain were "stabbing" and "tingling". This study documents the severity and course of chronic pain following SCI. PMID- 8212403 TI - [Relatives of psychotic patients: effect of group discussions and group education]. AB - Forty relatives of young psychotic patients participated in psychoeducative groups for eight sessions and filled in questionnaires at the first and the last session. They were questioned about user satisfaction, degree of strain, knowledge, attitude and behaviour in relation to mental illness, and the emotional climate in the family. The emotional climate in the family was investigated by means of the Family Questionnaire and divided in subscales, measuring criticism and over-involvement. The relatives had experienced strain in relation to the patient's behaviour. Aggression, unpredictability, dependence/helplessness were factors which the relatives felt most straining. The relatives' burden of care had consequences in economy, private life and working life. The relatives complained of lack of continuity in the treatment of the patient. Information about the condition, diagnosis and prognosis of the patient was criticized for being unsatisfactory, too vague or too scarce. After the psychoeducative group sessions, both criticism and over-involvement tended to fall (non-significant). The relatives were very satisfied with the group sessions. It is concluded that psychoeducative group sessions with relatives of psychotic patients are effective in influencing the emotional climate in the families in a desirable way. Better cooperation between psychiatric department/community mental health care centre, patient and relative can increase compliance with medical treatment and increase the relatives' ability to handle problems related to the patient's disease. PMID- 8212404 TI - [Higher mortality due to measles in Senegal for children with siblings of the opposite sex]. AB - The impact on case fatality of contracting measles infection from a sibling of the opposite sex was examined using data collected over a 20 year period in 31 isolated villages in Eastern Senegal. The interval between outbreaks of measles in a village was usually greater than ten years. During outbreaks, 766 children lived in families with two maternal siblings under ten years of age; 107 (14.0%) died of measles. The risk of dying of measles decreased with age, increased with the age difference between siblings and decreased with the size of the village. Adjusting for these factors, children in families with a boy and girl were found to have higher mortality than children in families with two boys or two girls (odds ratio (OR) = 1.81 (1.17-2.82)). The increase in risk was the same for boys and girls in male-female families. Cross-sex transmission of measles may be an important determinant of severity of infection. PMID- 8212406 TI - [Visceral leishmaniasis after a holiday in Malta]. AB - A case of visceral leishmaniasis in a 39-year-old woman is presented. It is the first case in Denmark, in an otherwise healthy person. The patient was infected on a short holiday in Malta. PMID- 8212405 TI - [Accidents affecting potato harvesters]. AB - During industrialization in agriculture, many farming machines have been introduced. It is well-known that farming is a dangerous workplace and that farm machinery cause many serious accidents every year. Four cases of accidents with potato harvesters are discussed. In three of four cases the farmers were injured while cleaning the machine without stopping it, which probably was the main cause of the accidents. Farmers are in general not careful enough when using farm machinery. Every year, farmers in Denmark are severely invalided in accidents with potato harvesters. A strategy to lower the accidents is proposed: 1. Information of farmers, farmer schools, machine constructors and importers about mechanisms of injury. 2. A better education of farmers in using potato harvesters (and other farming machines). 3. Better fencing of the potato harvesters. 4. If possibly constructional changes in the potato harvesters so things will not get stuck, or so that the machine will stop if things stuck. 5. Installation of switches on potato harvesters, which can be reached from all positions, stopping the machines immediately, or a remote switch control carried by the farmer. PMID- 8212407 TI - [Complement activation caused by beta-amyloid in Alzheimer's dementia]. PMID- 8212408 TI - [A case of pancreatic cancer]. PMID- 8212409 TI - A rat model for investigation of spinal mechanisms in detrusor instability associated with infravesical outflow obstruction. AB - A rat model of infravesical outflow obstruction was modified to allow cystometric investigation in conscious, free-moving animals after intrathecal drug administration. The catheter position and extent of drug distribution were controlled by injection of dye and dissection of the spinal canal. Continuous cystometries were performed in awake normal rats as well as rats with bladder hypertrophy and hyperactivity following infravesical outflow obstruction. In some animals of each group, cystometry was performed with simultaneous recording of intra-abdominal pressure. The possible effects of the presence of the intrathecal catheter were studied, as well as the effects of saline, local anesthetics, morphine and naloxone administered through the catheter. Neither the presence of the intrathecal catheter nor injection of saline affected the cystometric pattern. Bupivacaine (50 micrograms) produced paralysis of both lower extremities and a complete, though reversible, suppression of micturition in normal rats. In rats with hypertrophy, intrathecal bupivacaine in doses of 50 micrograms and 100 micrograms produced decreases in micturition pressure, increases in bladder capacity and dribbling incontinence. However, the amplitude of spontaneous contractile activity increased after the administration. The inhibitory effects of morphine (0.5-10 micrograms) on micturition in normal rats, which were rapidly reversed by naloxone, were in accordance with results obtained in previous studies in anesthetized animals. Rats with bladder hypertrophy showed a similar response to morphine and naloxone. However, the bladder hyperactivity was not inhibited by morphine. We conclude that the present model seems reliable for the study of spinal mechanisms in the development of detrusor instability associated with infravesical outflow obstruction. PMID- 8212410 TI - A technique for measurement of related values of pressure and cross-sectional area in the male urethra. AB - A probe for measurement of related values of cross-sectional area and pressure in the male urethra was constructed. The probe allows induction of variable pressures or fluid volumes in a distensible balloon located in the urethra and simultaneous recording of related values of cross-sectional area and pressure. Cross-sectional area is measured in the range of 11-102 mm2 using the field gradient principle. Pressure is measured in the range of 0-250 cmH2O using tip transducers. The time constant for cross-sectional area measurement is 0.02 s and that for pressure measurement, 0.007 s. The pressures required to reach the maximal and minimal cross-sectional areas of the balloon are 2.8 and -2.4 cmH2O, respectively. The shape of the probe after its placement in the urethra was studied by transrectal ultrasound in five volunteers. The results showed that the measurement error caused by the slope of the balloon walls or the forced bending of the catheter did not exceed 5%. The method enables a description of the biomechanical properties of the male urethra at rest in terms of estimated pressure at zero cross-sectional area, elastance, and stress-relaxation and at voluntary contraction in terms of work and power as evaluated at well-defined anatomical locations. PMID- 8212411 TI - Cell length measurements in longitudinal smooth muscle strips of the pig urinary bladder. AB - In this study the length of smooth muscle cells in muscle bundles of pig urinary bladder wall was determined after dissection in Tyrode buffers with different calcium concentrations ([Ca2+]). Previous studies have shown that the length of isolated smooth muscle cells decreases with an increase in [Ca2+] in the buffer. Unlike the results in isolated cells, no significant differences in length were found between cells in strips subjected to different [Ca2+]. Cells in bundles dissected from filled bladders were significantly larger than those dissected from emptied bladders. Cells in strips from emptied bladders dissected in 1.8 mM Ca(2+)-Tyrode buffer were shorter than those obtained in Ca(2+)-free buffer. From the measurements it was concluded that: (1) Cell length in intact tissue is directly related to tissue length; series elastic structures external to the cells do not allow significant shortening of the cells. (2) Passive parallel elasticity outside the cells accounts for passive shortening when bladders are emptied manually. (3) Cell length is not related to empty bladder weight. (4) A positive relation exists between empty bladder weight and bladder capacity. PMID- 8212412 TI - Response of urinary sodium excretion to elevated intravesical pressure. AB - This experimental study was designed to investigate the possibility of an interaction between elevated intravesical pressure and urinary sodium excretion. Fourteen male New Zealand rabbits were used. After performing a ureterocutaneous diversion, urinary sodium excretion was measured in two situations: with the bladder empty and with the bladder overdistended and an intravesical pressure of 60 cm H2O. There was a significant decrease in urinary sodium excretion at an elevated intravesical pressure. The urinary sodium excretion returned to normal after relief of the pressure. The results suggest the existence of a neurogenic pathway activated by the elevated intravesical pressure. PMID- 8212413 TI - Rare-earth elements in urinary calculi. AB - In vitro studies have demonstrated that trace elements have inhibitory as well as stimulatory effects on the crystallization of urinary stones. Little is known about the activities of rare-earth elements (REEs) in the human body. Although their physiological role is unclear, an effect on calcium transport mechanisms is discussed. In the present study, ten kidney stones (six oxalate and four phosphate stones) were analyzed by neutron-activation analysis for their REE patterns. Urinary stones are capable of concentrating these elements, and some fractionation into light and heavy REEs appears to take place during deposition. Significantly elevated concentrations of heavy REEs such as europium, terbium, and lutetium were detected in phosphate stones as compared with oxalate stones (P < 0.005). PMID- 8212414 TI - Effect of urinary macromolecules on aggregation of calcium oxalate in recurrent calcium stone formers and healthy. AB - The inhibitory activity of urinary macromolecules on the aggregation of calcium oxalate crystals was studied using an aggregometer originally devised to measure thrombocyte aggregation capacity by means of the optical turbidity at 660 nm. The macromolecular fraction of the urine (molecular weight above 5000) of recurrent calcium stone formers showed much less inhibitory activity than that of healthy controls (P < 0.05). It was speculated on the basis of the results of gel filtration that there were some proteins (molecular weight about 10,000-30,000) which had inhibitory activities for the aggregation of calcium oxalate. This gives support to the assumption that macromolecules are important during the phase of aggregation of calcium oxalate crystals. PMID- 8212415 TI - Relationship between the incidence infection stones and the magnesium-calcium ratio of tap water. AB - In a previous study we showed that the magnesium-calcium ratio of tap water is negatively correlated with the incidence of calcium-containing urinary stones. In this study we examined the relationship between the incidence of struvite stones, water hardness and the regional geological features on the basis of our previous study and an epidemiological study of urolithiasis performed in Japan. The magnesium-calcium ratio of tap water was found to correlate positively with the incidence of struvite stones. The tap water magnesium-calcium ratio was high in regions of basalt and sedimentary rock and was low in granite and limestone areas. The incidence of struvite stones in the regions of basalt and sedimentary rock was higher than that in the granite and limestone areas. Thus, this study suggested that the incidence of struvite stones is related to the magnesium calcium ratio of tap water and to the regional geology, as is the case for calcium-containing stones. PMID- 8212416 TI - Effects of high-energy shock waves on the viable human kidney. AB - Between September 1990 and July 1991, we treated 17 patients with renal-cell carcinoma by radical nephrectomy and two patients with urothelial carcinoma of the kidney pelvis by ureteronephrectomy. Immediately after nephrectomy, perfusion of the kidneys with cold HTK solution was performed and the organs were kept in hypothermia of 8 degrees C. The tumor-free parenchyma of the kidneys was treated 4 h later with shock waves of different energy levels in an experimental shock wave system (Siemens Company, Erlangen). Light microscopy and examinations by scanning laser microscopy were performed after treatment. High-energy shock waves (HESW) produce significant changes in the tubulary and blood-vessel system of the viable human kidney, depending on the energy applied. Although our model is limited by hypothermia of the explanted kidneys, the effects of shock waves on the organs can be studied. Our model is suitable for testing the effects of different lithotriptors on the human kidney. PMID- 8212417 TI - Determination of the energy-dependent extent of vascular damage caused by high energy shock waves in an umbilical cord model. AB - To determine the spatial extent of shock-wave-induced vascular damage human umbilical cords were exposed to electromagnetically generated, focused ultrasound waves of different energy densities. During treatment macroscopically visible hematoma and superficial holes appeared. Following exposure specimens were fixed and examined histologically. In addition to vessel wall necrosis and rupture, complete detachment of endothelial cells in defined regions was observed. A correlation of the extent of the damage with the energy density distribution revealed that a local energy density of 0.3 mJ/mm2 is the lower threshold for the occurrence of severe vascular damage. PMID- 8212418 TI - Possible advantages of aluminum-chloro-tetrasulfonated phthalocyanine over hematoporphyrin derivative as a photosensitizer in photodynamic therapy. AB - The potency of aluminum-chloro-tetrasulfonated phthalocyanine (AlS4Pc) as a photosensitizer in photodynamic therapy was evaluated in in vitro and in vivo studies. Compared with hematoporphyrin derivative (HpD), the following advantages of AlS4Pc were revealed: (1) AlS4Pc was less toxic than HpD in vitro without light irradiation. (2) AlS4Pc showed more photodynamic-dependent cytotoxicity and anti-tumor effect in the red area of the spectrum (> 660 nm) at which tissue penetration is high. (3) AlS4Pc appeared to be removed more rapidly from normal tissues such as muscle and skin. (4) AlS4Pc showed less photodynamic-dependent cytotoxicity in vitro and milder cutaneous phototoxicity in vivo with UVA irradiation. On the basis of these observations, AlS4Pc shows considerable promise as a photosensitizer for PDT. PMID- 8212419 TI - Dose-dependent half-life of glycine. AB - The serum concentration of glycine was measured at hourly intervals after administration of between 10 and 91 g glycine to 17 patients undergoing transurethral resection of the prostate and of between 15 and 22 g glycine to 18 volunteers by intravenous infusion. The apparent half-life of glycine varied 10 fold (range 26-245 min) and increased in direct proportion to the amount of glycine given. This result can be explained by assuming a marked intracellular accumulation of a surplus of glycine. The dose-dependent half-life means that patients who absorb large amounts of irrigating fluid are exposed to excessive blood levels of glycine for a prolonged period of time. PMID- 8212420 TI - Detection of endogenous receptors for carbohydrate ligands in primary and metastatic human renal cell carcinoma. AB - Frozen sections of primary and metastatic human renal cell carcinoma (RCC) were analyzed for the expression of endogenous binding sites for carbohydrates. Fluorescent neoglycoproteins, carrying chemically linked carbohydrate residues on bovine serum albumin as a carrier protein, were applied to 44 primary tumor specimens. In the majority of specimens, accessible binding sites with specificity for maltose and N-acetylgalactosamine were detected. In specimens of normal kidney no specific binding of carbohydrate ligands was observed under these experimental conditions. Specimens of both the primary tumor and a metastasis were available in 10 cases. When the expression of specific binding sites of primary tumors and metastases was compared, the respective patterns were similar with no clear gain or loss of certain lectins in the metastases. We conclude that binding sites with specificity for maltose and N acetylgalactosamine are present on human RCC and their corresponding metastases. PMID- 8212421 TI - Contact fibre Nd:YAG laser for partial nephrectomy: experimental study in pigs. AB - Thirty-two partial nephrectomies were performed without renal cooling on 13 pigs with a contact fibre Nd:YAG laser (10 W) or a steel scalpel with or without a vascular pedicle clamp. Nine pigs had a 2-week follow-up with an abdominal ultrasound 1 week postoperatively. The time for haemostasis was 6.9 +/- 5.2 min (mean +/- SD) with the laser and 9.1 +/- 5.8 min with the steel scalpel when the clamp was used (P = 0.028). There was no significant difference in the total operating time (13.2 +/- 4.5 min with the laser vs 12.6 +/- 4.6 min with the steel scalpel, P = 0.203). Intraoperative blood loss was similar in the two groups when the clamp was used. Clamping the renal pedicle decreased the blood loss by 61% in the laser group and 31% in the steel scalpel group. The number of ligatures used was significantly lower in the laser group (3.7 +/- 2.6) compared with the steel scalpel group (6.6 +/- 3.4) (P = 0.013). Five urinomas developed on the laser side and four on the steel scalpel side. These results indicate that the contact fibre Nd:YAG laser method can be used in partial nephrectomy, but it offers no definitive advantage over the conventional technique. PMID- 8212422 TI - [Immunotherapy of superficial bladder cancer]. AB - Because patients with superficial bladder cancer are in a high-risk group where tumor progression is concerned, topical therapeutic strategies are necessary to prevent tumor recurrence and tumor progression. Based on experimental studies and several case reports, during the last two decades immunotherapy for superficial bladder cancer has been developed. The effects of topical instillation of bacillus Calmette-Guerin (BCG) has been carefully investigated in numerous clinical trials. Especially patients with carcinoma in situ appear to benefit from BCG therapy. Other types of local immunotherapy, e.g., instillation of interferons, interleukins, and keyhole limpet hemocyanin have been found to have fewer side effects than BDG. These new approaches are currently under clinical investigation. PMID- 8212423 TI - [Immunotherapy of prostate cancer]. AB - In recent years immunotherapy of prostate cancer has developed into an innovative field of investigation. Nevertheless, in contrast to some other human tumors in which immunotherapy has been demonstrated to be effective, no breakthrough has been achieved with respect to a successful clinical application of this modality to prostate cancer. So far studies focus either on immunologically specific or nonspecific treatment concepts. Based on this, the modes of action of monoclonal antibodies, adoptive immunotherapy techniques, tumor cell vaccination, various biological response modifiers and substances with immunological as well as tumoritoxic/-static attributes are studied. Not all of the results obtained so far offer new insights into tumor biology. Ongoing studies in all fields continue to pursue immunological mechanisms for effective systemic therapy of prostate cancer. Major impulses may be seen only via immunologically specific concepts. Through these, new therapeutic modalities for patients with advanced prostate cancer may be developed which are more efficacious than androgen ablation. PMID- 8212424 TI - [Endoscopic lithotripsy with pneumatic shockwave (Swiss Lithoclast) using a mini ureteroscope]. AB - We performed endoscopic lithotripsy for 23 urinary stones (21 ureteral and 2 bladder stones) with a pneumatic shockwave unit (Swiss Lithoclast; EMS, Angiomed), for the first time applying the probe through the tangential working channel of a semirigid 6.9-Fr ureteroscope (Circon, ACMI). Disintegration was successful in all stones (5-24 mm). Immediately after treatment, the 2 patients with bladder calculi and 10 of the patients with ureteral stones (47.6%) were stone free, while another 5 had residual fragments < 3 mm. Migration of fragments in 4 patients (19%) led to subsequent extracorporeal shock wave lithotripsy. There were no ureteral perforations in this series. Routine application of double J stents avoided any serious postoperative complications. Endoscopic lithotripsy with the pneumatic shockwave unit was shown to be highly effective regardless of stone composition. The ltihotripsy probe is easily applied through mini ureteroscopes. PMID- 8212425 TI - [Laparoscopic training in urology. An essential principle of laparoscopic interventions in the retroperitoneum]. AB - The main problem with clinical introduction of laparoscopic techniques in urology is that despite experience with endoscopy no significant endoscopic training is given. Laparoscopic nephrectomy, in particular, is a rather complicated procedure and needs an adequate training concept: The beginner should have the possibility of practising in vitro in a closed "pelvi-trainer" to learn video-optical coordination and orientation; then it is necessary to get used to handling the instruments and practise the different steps of the procedure (i.e. clipping of vessels, sacking of the kidney) either in phantom models or in explanted animal organs. On this basis, we performed laparoscopic nephrectomy in an animal model (n = 18 porcine kidneys). We were able to standardize the technique of creating a pneumoperitoneum, the positioning of the animal, the site and size of the trocars, and preparation and clipping techniques (i.e. Endo-GIA) and entrapment of the kidney (testing different organ bags). A step-by-step approach was used for the introduction to clinical application. For simulation and training of video-assisted preparation techniques in patients and step-wise introduction to laparoscopy (instruments, endocoagulation, trocars), we created a "lap-tent", which was placed over the wound after exposition of Gerota's fascia. Further preparation was performed under laparoscopic conditions (without pneumoperitoneum) with a limited time allowed (1 h). Thereafter, we started with time-limited laparoscopy and laparoscopic lymphadenectomy prior to pelvic surgery (prostatectomy, cystectomy) to introduce the staff to the technique of pneumoperitoneum and placement of the trocars and to the use of the instruments in general. Based on this step-by-step training concept, after a 6-months period we were successful in introducing transperitoneal laparoscopic nephrectomy (TLN) to our clinical routine. So far, we have performed 20 laparoscopic nephrectomies, 1 nephro-ureterectomy, 4 tumour nephrectomies (inducing adrenalectomy), 2 adrenalectomies, and 6 modified retroperitoneal lymphadenectomies. In the lesser pelvis we have experience with 20 laparoscopic varicocelectomies, 23 pelvic lymphadenectomies, and 5 diagnostic laparoscopies for cryptorchidism (February 1993). PMID- 8212426 TI - [Value of transrectal ultrasound in determining the T-stage of prostate cancer]. AB - Accurate preoperative staging of prostate adenocarcinoma is especially important before radical prostatectomy. The purpose of this prospective study was to investigate the staging accuracy of transrectal ultrasonography in prostatic adenocarcinoma. The results of the preoperative staging evaluation in 126 patients with endorectal ultrasound were compared with the histopathologic findings after radical prostatectomy. Correct staging by transrectal sonography was possible in 82 of 126 patients (65%). For stage pT3 tumors, sensitivity, specificity and positive predictive value were 69%, 51% and 82% respectively. PMID- 8212427 TI - [Mechanical pressure regulator for transurethral surgery of the bladder]. AB - A new device is presented, rendering to constant pressure conditions during transurethral operations without need of intravesical pressure determination. Using a double sheath resectoscope the device is solely connected to the irrigation system. By backflow, intravesical pressure changes are transmitted to a membrane within the device. Irrigation is then controlled accordingly by a connected valve. In order to adapt bladder configuration to a situation ideal for performing resections, intravesical pressure can be set manually by regulating the tension of the membrane with a spring. PMID- 8212428 TI - [Renal oncocytoma. Diagnosis and its therapeutic consequences]. AB - The angiographic findings (hypovascularity, spokewheel phenomenon, lucent rim, linear course of vessels) and CT features (central scar, hyperdense without contrast medium) of 20 patients with renal oncocytomas were analyzed. Simultaneously seven patients with renal cell carcinoma preoperatively misdiagnosed as oncocytoma were compared and critically discussed. Preoperatively, reliable differentiation of renal oncocytoma and renal carcinoma is not possible. Nevertheless, in the presence of features typical for oncocytoma the operative strategy should be "kidney-preserving surgery". PMID- 8212429 TI - [Pathologic development of the kidney]. AB - In the absence of firmly established views on the development of nephropathy, we describe in this paper the embryogenetic and clinical aspects of kidney disease. Congenital reductive nephropathy always arises in the ureteral bud and is determined by two factors, endogenous dysplasia and endogenous obstruction. The nine well-known patterns of disease that may result are described herein. The most important starting points are as follows: (a) A dysplastically disorganized and hence refluxive trigone of the bladder induces, via pyramidal-medullary deficiencies, a defect of the metanephros and thus what we term reflux nephropathy (III-V). BU and PN may supervene postnatally. (b) Similarly, obstruction of the ureteral outlet in the first trimester induces dysplastic ascending nephropathy. (c) The same obstruction beginning in the second trimester induces nondysplastic, purely obstructive nephropathy, characterized by glomerular hypogenesis and hemo-obliterative cirrhosis which varies considerably from stage to stage and from case to case and may go as far as complete loss of the parenchyma. (d) Obstruction of the pyeloureteral junction, occurring late in the embryonic phase and originating outside the urinary system, provides the clearest example of fully developed nondysplastic reductive nephropathy. The lesional process may come to a halt at any time. (e) Coincidence of early embryonic dysplastic-refluxive nephropathy and late embryonic infravesical obstruction (with no causal link) accounts for half the morbidity from valvular disease. The other half results from simple nondysplastic obstruction. PMID- 8212430 TI - [Parameters influencing the incidence of recurrent urinary calculus after ESWL]. AB - With extracorporeal shock wave lithotripsy, stone fragmentation and the potential creation of residual stones has become an integral part of the treatment strategy. Therefore, true recurrence, regrowth and pseudo-recurrence determine the rate of new stone formation. In nonselected series the overall recurrence rate after ESWL varies between 6% after 1 year and 20% after 4 years. The comparison between recurrence rate after ESWL and the natural recurrence rate reveals that the results of ESWL are better than expected. Lithotripsy has no specific effect on true stone recurrence, and even the pseudo-recurrence is of minor clinical significance. Nevertheless, metaphylaxis keeps its place in treatment of recurrent urolithiasis. PMID- 8212431 TI - [Course of tissue acidosis, lactic acid production and morphologic changes in testicular tissue during ischemia. Effect of hypothermic measures]. AB - More than 90% of patients with testicular torsion lose their testis, either because orchiectomy is necessary or because ischaemic atrophy develops. The critical time before irreversible changes to the testis have taken place is, according to literature, 4-6 h. The aim of our study was to measure the tissue acidification (pH) in the testis at different temperatures and to estimate the effect of cooling on pH, lactate accumulation and morphological changes. In 36 human testes (obtained by orchiectomy in patients with metastatic prostate cancer) we measured the tissue acidification (pH), the tissue lactate level and the morphological changes at temperatures of 35, 25, 15 and 5 degrees C. We also measured the same parameters in 12 testes taken from young dogs. At the normal testicular temperature of about 35 degrees C the pH falls to 6.0 within 1 h of ischaemia. Cooling to 15 degrees C can extend this time to 6 h. The tissue lactate level rises from 25 mumol/gdw to nearly 200 mumol/gdw at 35 degrees C. The morphology of semithin sections of the testis shows swelling of the intratubular tissue (spermatogenesis) with loss of the interstitial space. Reducing temperature can also slow-down these changes. The critical pH value of the testis beyond which irreversible changes take place is not known; a pH of less than 6.0 is thought to be the probable threshold. PMID- 8212432 TI - [Trauma in urology]. PMID- 8212434 TI - Ureteroscopy for lower ureteral stones. PMID- 8212433 TI - ESWL: distal ureteral stone management--1993. PMID- 8212435 TI - Polycystic renal disease. AB - Renal cystic disease is a relatively common disorder whose development and progression currently appear to be due to an interaction between an abnormal basement membrane matrix, a potentially immature, hyperproliferative epithelium, and an abnormal epithelial secretory apparatus. RCC risk in cystic kidneys is the most controversial sequela of PKD. Currently, RCC risk in ESRD patients appears to be close to that present in the general population and only coincidentally associated with renal cysts. Screening of all ESRD patients for RCC and prophylactic native nephrectomy in dialysis and transplant patients does not seem to be indicated. PMID- 8212436 TI - Laparoscopic nephrectomy in crossed fused renal ectopia. AB - Operative laparoscopy offers the patient a minimally invasive alternative to open surgery. We have recently performed a laparoscopic nephrectomy of the upper moiety of a crossed fused renal ectopia. The procedure lasted approximately six hours, and the patient was discharged on postoperative day 3. He was able to resume normal physical activity in one week. This case demonstrates the advantages of minimally invasive surgery. PMID- 8212437 TI - Hsp-27 has no diagnostic or prognostic significance in prostate or bladder cancers. AB - Heat shock protein 27 (hsp-27) is a cytosol protein of unknown function that is concentrated in many estrogen-sensitive normal target organs and is expressed to a varying degree in many tumors, including ductal carcinoma of the breast, malignant fibrous histiocytoma (MFH) of the soft tissues, adenocarcinoma of the prostate, and transitional cell carcinoma (TCC) of the urinary bladder. Overexpression of hsp-27 has independent prognostic significance in patients with breast cancer and MFH, but its potential predictive value with prostate and bladder cancers has not been evaluated. Differential expression of hsp-27 may occur between invasive cancer and host tissue that could aid in diagnosis, and varying expression among invasive cancers may have potential prognostic significance that could influence the use of adjuvant therapy. To test these hypotheses, hsp-27 expression was evaluated by immunohistochemistry in archival formalin-fixed paraffin-embedded sections of primary prostate and bladder carcinomas where the outcome of the patient was known. In 36 prostate cancer specimens from patients who had undergone radical prostatectomy (Stages T1, T2; N0; M0), no normal glandular elements or invasive cancers expressed this protein. In 24 bladder cancer specimens from patients who had undergone radical cystectomy (Stages T2, T3A, T3B, T4A; N0, N1; M0), 12 (50%) cancers overexpressed this protein. Hsp-27 did not correlate with degree of histologic differentiation, T stage, nodal status, local recurrence, metastases, or survival. From these observations, we conclude that hsp-27 expression has neither diagnostic nor prognostic significance and will not serve as a predictive biologic marker with these important genitourinary cancers. PMID- 8212438 TI - Rectal injury occurring at radical retropubic prostatectomy for prostate cancer: etiology and treatment. AB - Of 2,212 patients who underwent radical retropubic prostatectomy for the treatment of prostate cancer, 27 had documented rectal injuries. All but one were detected immediately at the time of surgery and were repaired; a temporary diverting colostomy was established in 6 patients. Follow-up on these patients ranged from nine to one hundred eighty-five months (mean, 68 months). Four patients had fistulas between the rectum and the urinary tract that required additional surgery. Factors that predisposed patients for intraoperative injury to the rectum include a history of previous pelvic radiation therapy, previous rectal surgery, and previous transurethral resection of the prostate (P < 0.01). Higher local tumor stage did not significantly increase the risk of rectal injury at the time of radical retropubic prostatectomy. Preoperative bowel preparation may obviate colostomy; it may still be necessary in high-risk patients with suboptimal local repair. PMID- 8212439 TI - Thromboembolic complications following radical retropubic prostatectomy. Influence of external sequential pneumatic compression devices. AB - The influence of external sequential compression devices (SCD) on the development of postoperative thromboembolic events was studied in 1,300 consecutive men undergoing radical retropubic prostatectomy. Of the 784 men whose perioperative management did not involve the SCD, in 9 (1.1%) thromboembolic complications developed: 7 (0.9%) pulmonary emboli (PE), and 2 (0.3%) deep venous thrombosis (DVT). In the 516 patients with SCD prophylaxis there were 12 (2.3%) thromboembolic complications: 9 (1.7%) PE, and 3 (0.6%) DVT. In patients with SCD prophylaxis, the delay from the time of surgery to the onset of thromboembolic symptoms averaged 20 +/- 12 days, and all but 1 patient suffered the complication while an outpatient; this was significantly longer than in men without SCD (11 +/ 5 days; p < 0.05). This delay in thromboembolic events was the only benefit we could demonstrate with SCD. Recognizing that most thromboembolic complications occur after discharge, new strategies for prophylaxis may be needed during this period, and patients should be well informed about the signs and symptoms of PE and DVT to avoid a delay in diagnosis and treatment. PMID- 8212440 TI - Effect of nitric oxide-donor, linsidomine chlorhydrate, in treatment of human erectile dysfunction caused by venous leakage. AB - Recent experimental work has demonstrated that nitric oxide (NO) is the neurotransmitter responsible for cavernous smooth muscle relaxation. We studied the effect of a direct NO-donor, linsidomine chlorhydrate (SIN-1), in 30 patients with venous leakage confirmed by dynamic pharmacocavernosography and pharmacocavernosometry that was refractory to prostaglandin E1 (PGE1) under the assumption that the more physiologic approach might give better results. In all 30 patients, response to SIN-1 was no better, and in 22 cases it was less than the response to PGE1. No systemic or local side effects of SIN-1 were observed. SIN-1 is not superior to PGE1 in the treatment of erectile dysfunction caused by venous leakage, and failure of NO-mediated smooth muscle relaxation does not play a part in the entity, "venous leakage." PMID- 8212441 TI - Nonoperative management of blunt pediatric major renal trauma. AB - Although algorithms exist for the management of renal trauma in adults, guidelines have not been established in children. Of 1,175 patients entered into our Trauma Registry between 1987 and 1991, 61 (5.2%) presented with gross or microscopic hematuria. Eight of the 58 patients (13.8%) who had blunt abdominal trauma had major renal injuries. Gross hematuria (n = 10) was a significant predictor of major renal injury (n = 5) (p < 0.001). All 3 patients with microscopic hematuria and a major renal injury also had evidence of multisystem trauma. Admission blood pressure, hemoglobin, and trauma score were not predictors of major renal trauma. All cases were managed nonoperatively except for 1 patient who required a partial nephrectomy for continued hemorrhage. These data suggest that hematuria of any degree should be evaluated in the pediatric population, since major injuries can occur with even microscopic hematuria or in the absence of shock. Nonoperative management in this series resulted in no morbidity or delayed complications and suggests that surgical exploration be reserved for ongoing bleeding. PMID- 8212442 TI - Management of urachal anomalies in children and adults. AB - During a period of fifteen years, 9 children and 5 adults with a variety of urachal anomalies were treated. Infected urachal cysts were more common in children whereas adults more frequently had infected urachal sinuses. After careful physical examination, a preoperative diagnosis could be made in most patients, with ultrasound examination decisive in doubtful cases. Whenever feasible, complete excision of the umbilicovesical tract is performed, but in very ill patients, a staged treatment becomes necessary. The preoperative injection of methylene blue is helpful in the identification of communicating tracts, all of which should be removed. All affected children should undergo investigation for associated genitourinary anomalies. PMID- 8212443 TI - Experience with AS 800 artificial sphincter in pediatric and young adult patients. AB - Congenital or acquired sphincteric urinary incontinence in children and young adults is a severe social and physical burden. As a therapeutic option, we implanted 61 AS 800 artificial sphincters in 59 patients (46 males and 13 females). The mean age of the patients was 17.5 years (range, 6 to 34 years), and mean follow-up was forty-three months (range, 5 to 84 months). In addition to artificial sphincter implantation, intestinal cystoplasty was required in 22 patients to obviate problems of increased detrusor contractility or decreased detrusor compliance, or both. Continence was good in 47 patients (80%) and fair in 8 (14%). Four patients (7%) were awaiting sphincter modification or cystoplasty, or both. Careful and prolonged follow-up is mandatory in all patients managed in this fashion to preclude the deleterious effects of subtle changes in detrusor or ureteral function on the integrity of the upper urinary tracts. PMID- 8212444 TI - Resection of papillary transitional cell carcinoma using endoscopic snare. AB - We describe a method to remove papillary transitional cell carcinoma of the bladder using an adapted colonoscopic snare for transurethral electroresection. This method permits safe and accurate resection of papillary bladder tumors without the complications associated with the use of the resectoscope. PMID- 8212445 TI - Optical valvulotomy for urethral valves using a hook-blade cold knife. AB - Endoscopic disruption of urethral valves remains a mainstay of the pediatric urologic armamentarium. We describe transurethral optical valvulotomy using a hook-blade cold knife as a safer alternative to valve resection using a wire loop electrode. This technique offers precise control of the resection process and freedom from inadvertent injury to the urethra or sphincter due to a "hot" electrode. PMID- 8212446 TI - Spontaneous rupture of renal cell carcinoma associated with acute pancreatitis. PMID- 8212447 TI - Transitional cell carcinoma of bladder in children and adolescents. AB - Transitional cell carcinoma of the bladder is rare in patients under sixteen years of age. A case is described in a ten-year-old boy, and the literature is reviewed. The diagnosis and treatment of this tumor is the same in childhood as in older patients. Recurrence as well as death have been reported in this age group; therefore, these patients warrant careful long-term follow-up. PMID- 8212448 TI - Tortuous and aberrant external iliac artery precluding radical retropubic prostatectomy for prostate cancer. AB - A sixty-eight-year-old black man with clinical Stage A1 (T1a) adenocarcinoma of the prostate was found to have a tortuous and redundant left external iliac artery directly overlying the superior aspect of the prostate gland. The location of this blood vessel precluded radical retropubic prostatectomy. To our knowledge, this is the first reported example of this clinical situation. Computer-generated three-dimensional imaging from the computed tomography scan allowed accurate assessment of the vascular anomaly. PMID- 8212449 TI - Testis tumor in an adult presenting with torsion of testis. PMID- 8212450 TI - Laparoscopic use of the ureteral illuminator. AB - Laparoscopic identification of the ureters is complicated by decreased tactile sensation and magnified video imaging. We report our experience in placing a ureteral illuminator to aid in ureteral identification prior to six laparoscopic urologic procedures. The ureteral illuminator facilitated laparoscopic ureteral identification during five nephoureterectomies and one ureterolithotomy. Illuminator placement required a minimum of anesthetic time and resulted in no complications. Preoperative placement of a ureteral illuminator aids laparoscopic ureteral identification and may reduce the incidence of inadvertent ureteral injury. PMID- 8212451 TI - Periurethral collagen for urinary incontinence after gender reassignment surgery. AB - We report on 2 patients, one female and one male transsexual; in both, Type III stress urinary incontinence developed after gender reassignment surgery. Both patients were treated by periurethral injection of gluteraldehyde cross-linked collagen resulting in a marked symptomatic improvement in association with a significant rise in abdominal leak point pressures. We believe these are the first reported cases of collagen injection being used for urinary incontinence after gender reassignment surgery. PMID- 8212452 TI - Tumor suppressor genes in urologic tumors. AB - During the last decade remarkable progress has been made in our understanding of the malignant phenotype. There is evidence that a series of genetic changes are involved in the conversion of a normal cell to a malignant one. These changes have been directly identified with mutations in various genes usually involved in cell growth and proliferation. Two main classes of genes have been characterized: oncogenes, which promote growth and tumor suppressor genes, which restrain growth. While oncogenes have been studied in relative detail, little is known about tumor suppressor genes. However recent studies revealed that loss of tumor suppressor genes are a common mechanism for the progression of cancer and are of prognostic value. In this review we focus on the role of these tumor suppressor genes in urologic tumors in experimental as well as clinical studies. PMID- 8212453 TI - Pathophysiology of erectile dysfunction. AB - During the past decade, our knowledge of the hemodynamics, functional anatomy, neurophysiology, and neuropharmacology of erectile function has evolved substantially. The change of smooth muscle tone has emerged as a key factor in erection and detumescence. However, future studies are needed to elucidate the cellular and molecular basis of erectile physiology. With insight into normal physiology we will understand the pathologic process and be able to treat it. PMID- 8212454 TI - Islet amyloid polypeptide: a review of its biology and potential roles in the pathogenesis of diabetes mellitus. AB - Islet amyloidosis (IA) is the principal lesion in the endocrine pancreas of human beings with non-insulin-dependent diabetes mellitus (NIDDM) and in the similar forms of diabetes mellitus in domestic cats and macaques. As such, the delineation of the pathogenesis of this form of amyloidosis may be crucial to the understanding of the development and progression of NIDDM. Islet amyloid polypeptide (IAPP) is a recently discovered polypeptide that is the principal constituent of IA in human beings, cats, and macaques. IAPP is produced by the pancreatic beta-cells and is co-packaged with insulin in the beta-cell secretory vesicles. Immunohistochemical and physiologic evidence supports the notion that the beta-cells are heterogenous with respect to their relative contents of insulin and IAPP. Therefore, although IAPP is co-secreted with insulin in response to a variety of well-known insulin secretagogues, the molar ratio of these two proteins that is released from the islets may vary, depending upon the glucose concentration and prevailing metabolic milieu. IAPP is highly conserved among mammalian species and has about 45% homology to another neuropeptide, calcitonin gene-related peptide. IAPP is encoded by a single-copy gene located, in the human being, on chromosome 12. IAPP is expressed as a 93 (murine)-89 (human)-amino acid prepropolypeptide that is processed enzymatically, resulting in the removal of amino- and carboxy-terminal propeptide segments. The 20-29 region of the IAPP molecule is most important in the ability of IAPP to form amyloid fibrils. The role of IAPP and IA in the pathogenesis of human NIDDM and similar forms of diabetes mellitus in cats and macaques may involve several possible mechanisms, including 1) direct physical/chemical damage to beta-cells, resulting in necrosis and loss of functional islet tissue, 2) biologic activities of IAPP that oppose those of insulin or abnormally suppress insulin secretion, and 3) interference by IA deposits of passage of insulin out of beta-cells and/or entrance of glucose and other secretogogues into the islet. The roles of each of these possible mechanisms have yet to be demonstrated. In addition, the physiological significance of the apparent IAPP deficiency in both insulin dependent diabetes mellitus and NIDDM is currently unknown. PMID- 8212455 TI - Peanut agglutinin lectin immunohistochemical staining of normal and neoplastic canine tissues. AB - Peanut lectin binding sites were demonstrated in normal canine tissues and in 114 canine tumors by avidin biotin complex immunohistochemical staining on unfixed cryostat tissue sections. Peanut agglutinin (PNA) receptors occurred in a variety of normal cells and tissues, including lymphoid follicle center cells; cortical thymocytes; basal cells and the stratum spinosum of stratified squamous epithelium; columnar epithelium of the gastrointestinal tract; parietal cells and chief cells of the stomach; some endothelial cells; myelin; chondrocytes; spermatogenic cells; cells of the adrenal medulla; Bowman's capsule and the distal convoluted tubules of the kidney; prostatic, perianal and endometrial epithelium; and the extracellular matrix of connective tissues. Neoplastic cell staining was sporadic and was most often observed in benign or well differentiated neoplastic tissues in which the corresponding normal cells also expressed PNA binding sites. However, PNA also bound to some tumor cells in which the analogous normal tissues were unstained, including cells of some fibrosarcomas, rhabdomyosarcomas, hemangiopericytomas and proliferating myoepithelial cells in mixed mammary tumors. Although PNA binding is complex and heterogeneous in canine tissues and does not appear to immunohistochemically detect a moiety associated with neoplastic transformation per se in the majority of canine tumors, the expression of PNA receptors may be associated with neoplastic changes in some mesenchymal cell populations. PMID- 8212456 TI - Subepidermal vesiculobullous filarial dermatitis in free-ranging American badgers (Taxidea taxus). AB - Skin and superficial lymph nodes from the 65 juvenile (< 1 year old) and adult free-ranging American badgers (Taxidea taxus) of both sexes that were killed from late July to late October 1991 as part of the recovery program for the endangered black-footed ferret (Mustela nigripes) were examined for evidence of Filaria taxideae. Fifty-one badgers (51/64, 80%) were infected. Both adult badgers (30/32, 94%) and juvenile badgers (21/32, 67%) were infected by adult filarial worms, which occurred most commonly in subcutaneous tissues of the inguinal area, proximal thigh, and ventral abdomen. Sections of formalin-fixed skin and, from many badgers, subcutaneous lymph nodes were stained with hematoxylin and eosin, Jones' methenamine silver (for basement membrane), and an avidin biotin peroxidase complex method (for factor VIII-related antigen). Superficial dermatitis attributable to embryonated filarial ova and larvae was present in 26/64 badgers (41%), all of them adult (> 1 year old). Acute lesions consisted of multifocal vesiculobullous dermoepidermal separation and superficial perivascular dermatitis. Ultrastructural examination and Jones' silver-stained sections revealed separation between basal keratinocytes and the basal lamina (subepidermal vesiculation). Older lesions consisted of ulcerative superficial granulomatous dermatitis associated with ova and larvae. Multifocal granulomatous endolymphangitis, which involved afferent lymphatics of subcutaneous lymph nodes, was associated with viable as well as degenerative ova and larvae. Adult filarial worms were found in the subcutis alone and did not provoke an inflammatory reaction. PMID- 8212457 TI - The expression of keratins, vimentin, neurofilament proteins, smooth muscle actin, neuron-specific enolase, and synaptophysin in tumors of the specific glands in the canine anal region. AB - Eight canine tumors originating from specific glandular structures in the anal region, as well as metastatic tumor tissue of two of these cases (case Nos. 7, 8), were immunohistochemically analyzed using various monoclonal antibodies (MoAbs) directed against human keratin types, vimentin, neurofilament proteins, and alpha-smooth muscle actin. These tumors also were stained for the broad spectrum neuroendocrine markers neuron-specific enolase (NSE) and synaptophysin. In histologically normal canine anal structures, alpha-smooth muscle actin and NSE antibodies stained basally localized (probably myoepithelial) cells in the anal glands and the anal sac glands. NSE staining also was present in a limited number of luminal cells in both anal glands and anal sac glands. Synaptophysin labeling was not observed in any of these glandular structures. Histologically, the tumors were differentiated into well- and moderately differentiated perianal gland tumors (n = 5) and carcinomas without perianal gland differentiation (n = 3), corresponding to the so-called apocrine carcinomas of the anal region. Immunohistochemically, the perianal gland tumors could be differentiated from the carcinomas by marked differences in staining pattern with the various keratin MoAbs, particularly MoAbs directed against human keratin types 7 and 18. The keratin-staining characteristics of the carcinomas suggest a glandular luminal cell origin. Metastases of the carcinomas showed loss of some keratin-staining characteristics as compared with the primary tumor. Staining for NSE was only observed in solitary cells and small cell clusters in the carcinomas and their metastases, whereas the alpha-smooth muscle actin antibody did not react with the carcinoma cells. None of the tumors stained for neurofilament proteins or synaptophysin. An unequivocal neuroendocrine nature of the carcinomas could not be substantiated by our immunohistochemical study, although the presence of a population of neuroendocrine cells within these neoplasms seems likely. Because the immunohistochemical features of the carcinomas with respect to various keratin MoAbs and NSE are similar to those of the anal glands and the anal sac glands, both these glands might be considered as site of origin of these carcinomas. PMID- 8212459 TI - Granulomatous enteritis in a dromedary (Camelus dromedarius) due to green algal infection. PMID- 8212460 TI - A trematode (Phagicola sp.)-induced mesenteric lymphadenitis and enteritis in raccoons (Procyon lotor). PMID- 8212458 TI - Leptospirosis in equine fetuses, stillborn foals, and placentas. AB - Leptospirosis was diagnosed in 51 equine fetuses and 16 stillborn foals with gestational ages from 3 1/2 to 11 months. Diagnosis was based on one or more of the following: positive fetal antibody titer, positive fluorescent antibody test, demonstration of spirochetes in kidney and/or placental sections stained by the Warthin-Starry technique, high leptospiral titers in aborting mares, or isolation of Leptospira spp. from fetal organs. Gross lesions were observed in 80.3% of the fetuses, stillborn foals, and placentas. Gross placental lesions included nodular cystic allantoic masses, edema, areas of necrosis of the chorion, and necrotic mucoid exudate coating the chorion. The liver (23 cases) was enlarged, mottled, and pale to yellow. The kidneys (seven cases) were swollen and edematous with pale white radiating streaks in cortex and medulla. Microscopic lesions were observed in 96% of fetuses, stillborn foals, and placentas. Placental lesions consisted of thrombosis, vasculitis, mixed inflammatory cell infiltration of the stroma and villi, cystic adenomatous hyperplasia of allantoic epithelium, and villous necrosis and calcification. Fetal lesions included hepatocellular dissociation, mixed leukocytic infiltration of the portal triads, giant cell hepatopathy, suppurative and nonsuppurative nephritis, pulmonary hemorrhages, pneumonia, and myocarditis. Spirochetes were demonstrated with the Warthin-Starry stain in the allantochorion and/or kidney of 69 of the 71 cases. Using the direct fluorescent antibody technique, 56/60 cases tested positively for leptospires. Leptospires were isolated from fetal tissues in 20/42 cases. Sixteen of the isolates were identified by restriction enzyme analysis as Leptospira interrogans serogroup Pomona serovar kennewicki; case Nos. 36 and 41 were serovar grippotyphosa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212461 TI - Enterogenous cysts in chickens. PMID- 8212462 TI - Granulomatous lymphangitis associated with interstitial pulmonary emphysema in adult cows. PMID- 8212463 TI - Ubiquitinated inclusions in brains from Salers calves with beta-mannosidosis. PMID- 8212464 TI - Cerebellar abiotrophy characterized by granular cell loss in a Brittany. PMID- 8212465 TI - Hypomyelination of the central nervous system of two Siamese kitten littermates. PMID- 8212466 TI - Hyperplastic gastritis with intraepithelial Campylobacter-like organisms in a Beagle dog. PMID- 8212467 TI - Spontaneous pleomorphic adenoma in the submandibular salivary gland of an aged male (C57BL/6N x C3H/HeN)F1 (B6C3F1) mouse. PMID- 8212468 TI - Embryonal rhabdomyosarcoma in a sheep. PMID- 8212469 TI - Eva vaccine granted animal test certificate. PMID- 8212470 TI - Cat scratch disease organism found. PMID- 8212471 TI - Further studies of the application of live Salmonella enteritidis aroA vaccines in chickens. AB - A model was developed to simulate the lateral spread of Salmonella enteritidis infection among chickens. One group of newly hatched chicks was vaccinated orally with S enteritidis aroA. At three weeks old naive chickens were infected with a wild-type strain of S enteritidis and brought into contact with separate groups of aroA vaccinated chickens and unvaccinated control chickens. The vaccinated chickens were well protected against colonisation of the gut by the wild-type strain whereas the control group became heavily colonised. The IgG responses to a lipopolysaccharide extract of S enteritidis in the vaccinated chickens indicated a limitation of invasion from the gut. Chickens vaccinated orally at one day old with S enteritidis aroA were not protected against oral or intravenous challenge at eight weeks old with a wild-type strain of S typhimurium. A group of newly hatched female chicks was vaccinated orally with S enteritidis aroA and again at two weeks old. A second group also received oral booster doses at 16 and 18 weeks. When challenged intravenously with a wild-type strain of S enteritidis at 23 weeks old there was a significant reduction in the numbers of this strain in the spleens, livers, ovaries and caeca of both vaccinated groups. Booster vaccination at 16 and 18 weeks of age induced the greatest protection of the caeca. PMID- 8212472 TI - Piglets born after transcervical transfer of embryos into recipient gilts. AB - A method is described for the non-surgical transfer of embryos in pigs. Embryos at the 8-cell to the hatched blastocyst stage, recovered on days 4 to 7 of the oestrous cycle by flushing the oviducts and uteri of superovulated donors, were transferred transcervically into the uterine body of anaesthetised recipient gilts using a sterile disposable plastic spiral catheter and an embryo transfer cannula. Fifty-eight non-surgical transfers have been performed and six pregnancies were established. Eight and three normal fetuses were recovered from two recipients slaughtered between 35 and 45 days after embryo transfer. Three recipients came to term and gave birth to litters of two, six and seven living piglets. One recipient aborted between 45 and 60 days of gestation. PMID- 8212473 TI - Increased reproductive losses in cattle infected with bovine pestivirus around the time of insemination. AB - Unmated heifers seronegative to bovine pestivirus were used to investigate the effects on conception and embryo-fetal survival of pestivirus infection around the time of artificial insemination. The reproductive performances of three groups were compared; the control group did not become infected during pregnancy, group 1 heifers were infected by contact with a persistently infected cow and calf four days after insemination and group 2 heifers were infected intranasally nine days before insemination. Conception rates and embryo-fetal survival were monitored by serial serum progesterone assays, transrectal ultrasonography and manual palpation of the uterus. The conception rates (determined 20 days after insemination) of 60 per cent (nine of 15) and 44 per cent (eight of 18) for groups 1 and 2 were lower than the 79 per cent (11 of 14) achieved by the control group. The group 1 heifers subsequently experienced significant embryo-fetal loss, resulting in a pregnancy rate (determined 77 days after insemination) of 33 per cent (five of 15), significantly lower than the control group's 79 per cent (11 of 14). The pregnancy rate of the group 2 heifers (39 per cent, seven of 18) was also significantly lower than that of the controls, largely as a result of the group's poor conception rate. All the heifers diagnosed pregnant 275 days after insemination were induced to calve. No persistently infected calves were born. PMID- 8212474 TI - Renal tubular acidosis in a mare. PMID- 8212475 TI - Docking of dogs. PMID- 8212476 TI - 'Seeing practice'. PMID- 8212477 TI - Docking of dogs. PMID- 8212478 TI - Duty of care. PMID- 8212480 TI - Homoeopathic nosodes. PMID- 8212479 TI - Control of foot-and-mouth disease. PMID- 8212481 TI - Splenic torsion in dogs. PMID- 8212482 TI - Issues arising from recent advances in biotechnology. AB - Biotechnology offers the potential for the benefit of both animals and humans, in terms of the prevention, treatment and diagnosis of disease, and improved agricultural productivity. By the same token, it raises questions in relation to the welfare of animals and care of the environment. In 1992, the BVA Animal Welfare Foundation set up a study group to consider the ethical and welfare concerns about the genetic manipulation of animals, and the production and use of genetically engineered organisms and products. Its report is published here. PMID- 8212483 TI - Epidemiological and diagnostic features of canine and feline dermatophytosis in the United Kingdom from 1956 to 1991. AB - Between 1956 and 1991, 8349 samples from dogs and cats were received for investigation of suspected dermatophytosis, and 1368 (16 per cent) yielded positive cultures. Cats had a significantly higher proportion of positive cultures (26 per cent) than dogs (10 per cent), and of these Microsporum canis accounted for 92 per cent in cats and 65 per cent in dogs. The other isolates were diverse but mainly sylvatic dermatophytes, and M gypseum was isolated on only four occasions. Different breeds of dog and cat had significantly different prevalences of infection, with pedigree and long-haired cats, and Jack Russell and Yorkshire terrier dogs having a particularly high proportion of positive cultures. Animals less than one year old appeared to be predisposed to infection, but there was no apparent sex predisposition and no conclusive evidence of any seasonal variation in the incidence of the disease. In comparison with the results of dermatophyte culture, examination under Wood's lamp had a positive predictive value of 90 per cent and a negative predictive value of 94 per cent in determining M canis infection, and direct microscopy had positive and negative predictive values of 93 per cent in determining the presence of dermatophytosis. However, cultural examination alone was insufficient for the diagnosis of dermatophytosis owing to the occurrence of false positive and false negative results. PMID- 8212484 TI - Some effects of nutrition and management on the fertility of dairy cattle. AB - When 24 cows were classified according to whether they had a better or worse energy status (defined as a plasma beta-hydroxybutyrate level below or above 15 mg/100 ml and a plasma glucose level above or below 55 mg/100 ml) the median interval between calving and the onset of cyclicity was shorter and conception rates were better for the cows with a better energy status at seven and 14 days after calving. This was not repeated when the cows' energy status was assessed as better at either 21 days after calving or at the time of service. In the same group of cows there was a positive correlation between the loss of condition score in early lactation and beta-hydroxybutyrate levels. In a further trial 15 cows fed a silage-based diet during the dry period had better conception rates and greater luteinising hormone responses to buserelin than 14 cows fed a straw based diet. The straw-fed cows lost more weight before calving and had significantly higher non-esterified fatty acid levels. After calving both groups of cows were fed the same diet but the cows fed straw in the dry period produced less milk and lost less weight than the cows fed silage. Dry cow nutrition affected subsequent fertility and production. The non-esterified fatty acid level in the last week or two of pregnancy is suggested as a practical indication of the level of dry cow nutrition and its probable effect on productivity. No relationships were observed between plasma urea concentrations and the fertility of the cows. PMID- 8212485 TI - Demonstration of the oral path of infection with Anaplasma marginale in calves. AB - When four calves were experimentally infected orally with blood infected with Anaplasma marginale they developed anaplasmosis after an average incubation period of 30 days, as demonstrated by the presence of the organism in blood films and positive titres in a complement fixation test. PMID- 8212486 TI - Lyme disease in Scotland: results of a serological study in sheep. PMID- 8212487 TI - Aetiology of rabbit haemorrhagic disease in China. PMID- 8212488 TI - Embryo production by in vitro techniques in dairy cattle in Greece. PMID- 8212489 TI - Animals in research. PMID- 8212490 TI - Control of hypomagnesaemia in cows. PMID- 8212491 TI - Conserving wildlife. PMID- 8212493 TI - Unusual case of choke. PMID- 8212492 TI - Sebaceous adenitis in the standard poodle. PMID- 8212494 TI - Associations between viral infections and respiratory disease in artificially reared calves. AB - Market-purchased, week-old, dairy bred calves entering a commercial calf-rearing unit were blood sampled at six-week intervals until three months old. Viral infections were monitored by ELISA for antibodies to bovine herpesvirus 1, bovine respiratory syncytial virus, parainfluenzavirus-3, bovine adenovirus subgroup 1 and bovine viral diarrhoea virus (BVDV). The immunoperoxidase test was used to detect BVDV in serum. The total immunoglobulin concentration in the initial blood sample was measured by the zinc sulphate turbidity test. The relationship between clinical respiratory disease, viral seroconversion and the initial concentration of serum immunoglobulin was investigated by the use of the relative risk statistic, Fisher's exact test, chi 2 techniques and the correlation coefficient. Treatment rates for respiratory disease of 45 per cent were observed during the first period of the study and 19 per cent during the second period. During the first period there was a significant positive association between clinical respiratory disease and seroconversion for all the viruses except parainfluenzavirus-3 and BVDV but in the second period there was no such relationship. Similarly, in the first period, but not in the second, there was a significant negative association between clinical respiratory disease and both antiviral immunoglobulin as measured by ELISA and total immunoglobulin as measured by the zinc sulphate turbidity test. Two of the 536 calves that survived to three months of age were found to be persistently infected with BVDV. PMID- 8212495 TI - An outbreak of Corynebacterium pseudotuberculosis infection in an Israeli dairy herd. AB - An outbreak of Corynebacterium pseudotuberculosis infection in an Israeli dairy herd appeared in four clinical forms: cutaneous, mastitic, visceral and a mixed form. Only cows were affected and susceptibility increased with age. Most cases occurred during a short period in the summer months. The total morbidity rate was 13.7 per cent involving 41 cows. Thirty cows were affected by the cutaneous form, five by the mastitic form, four by the mastitic and cutaneous forms, one by the mastitic and visceral forms and one by the visceral form. The cutaneous form appeared as one or two pyogranulomatous lesions affecting the body or head. Subclinical to severe clinical mastitis was found in the mastitic form. In the visceral form the upper and lower respiratory system were affected by multiple purulent lymphadenitis. All the cutaneous lesions recovered irrespective of treatment. Mastitis did not respond to treatment and severely affected milk production in most cases. All the isolates of C pseudotuberculosis were nitrate reductase negative. Most isolates were sensitive to norfloxacin, cephalothin, methicillin, kanamycin and furazolidone and resistant to ampicillin, lincomycin and neomycin. PMID- 8212496 TI - External quality assessment of the technical aspects of histopathology in veterinary laboratories: a pilot study. AB - The feasibility and acceptability of an external quality assurance scheme in veterinary histopathology were assessed for one year. The format of the scheme is described and the results are discussed. It is suggested that a self-financing scheme for all laboratories offering histopathological diagnosis should be introduced as a contribution to the maintenance of standards. PMID- 8212497 TI - A new ichthyotoxic dinoflagellate: cause of acute mortality in aquarium fishes. PMID- 8212498 TI - Differential diagnosis of suspected swine fever. PMID- 8212499 TI - Women in the profession. PMID- 8212500 TI - Biomechanical considerations in the treatment of navicular disease. AB - In recent years much attention has been paid to vascular studies of the navicular bone in health and disease; however, the relative importance of these studies has overshadowed biomechanical factors which may yet prove to be of importance. This paper outlines the pertinent anatomy, and discusses current concepts in the aetiology and pathogenesis of the disease. It describes the treatment regimens which are based on biomechanical considerations and compares the results of some currently employed techniques. All aspects of navicular disease remain controversial. This paper is not intended to review or debate all current information on the subject. It reviews information on only biomechanical considerations in an attempt to focus attention on these aspects of treatment. PMID- 8212501 TI - Idiopathic hepatic fibrosis in 15 dogs. AB - Idiopathic hepatic fibrosis was diagnosed by liver biopsy in 15 young dogs, of which nine were German shepherds. Clinical signs included ascites, anorexia, weight loss and hepatic encephalopathy. Erythrocyte microcytosis was a consistent clinical feature, and clinical chemistry generally revealed hypoproteinaemia and high serum activities of alkaline phosphatase and, to a smaller extent, alanine aminotransferase. Fasting blood ammonia and serum bile acid concentrations were increased in most dogs examined, and all the dogs tested had prolonged retention of sulfobromophthalein at 30 minutes. Multiple acquired portosystemic shunts were revealed by laparotomy and/or portography. Non-inflammatory fibrosis was present to different degrees in all the dogs' livers, and on the basis of its predominant location these were classified as having central perivenous fibrosis, diffuse pericellular fibrosis or periportal fibrosis. The response to symptomatic treatment and anti-fibrotic therapy with glucocorticosteroids or colchicine was variable. Seven dogs died or were euthanased shortly after diagnosis, but one dog survived two-and-a-half years, and three dogs were still alive more than four years after the initial diagnosis. PMID- 8212503 TI - Deaths in budgerigars associated with a paramyxovirus-like agent. PMID- 8212502 TI - A field study of meningoencephalitis in calves with particular reference to analysis of cerebrospinal fluid. AB - Meningoencephalitis was recorded in 10 two- to 14-day-old calves during a two year field study. Analysis of lumbosacral cerebrospinal fluid revealed a marked increase in protein concentration with a pronounced neutrophilic pleocytosis. Three calves with positive bacteriological cultures which were treated with chloramphenicol survived whereas six calves treated with penicillin G had to be destroyed on humane grounds after their condition deteriorated. Only two of the 10 calves had concurrent lesions of omphalophlebitis which may indicate that this is not the major route of bacterial invasion in neonatal meningoencephalitis. None of the constituents of cerebrospinal fluid proved to be a reliable prognostic indicator of meningoencephalitis. It is concluded that the analysis of cerebrospinal fluid is a useful ancillary aid in the investigation of abnormal mental states in neonatal calves and a sensitive test for the presence of an inflammatory lesion involving the leptomeninges. PMID- 8212504 TI - Overestimation of copper deficiency. PMID- 8212505 TI - Basis for the evaluation of the microbiological risks due to veterinary drug residues in food. AB - The history of the establishment of safe residue levels is reviewed. Current international agreements within the FAO/WHO Codex Alimentarius programme and EC legislation establish these levels on the basis of toxicology studies. In addition to conventional toxicological effects, other effects such as the effects of drugs on the immune system, and pharmacological effects should be taken into account. The latter also include specific effects of residues of veterinary antibiotics on the human gut flora. The methods for the assessment of these effects are evaluated. Studies in human volunteers enable the establishment of a no-effect level in conditions which are the most closely mimicking the conditions of use. However, they are less favourable from a practical and ethical point of view. Studies with animal models can be used; for example human intestinal flora can be inoculated to gnotobiotic mice. These models need nevertheless to be further validated. Studies in vitro, such as those to determine the MIC, are relatively simple to carry out and inexpensive, but are not always representative of the relevant bacteria, and may not take into account factors such as, Ph, anaerobiosis and the barrier effect. PMID- 8212506 TI - The effect of antimicrobial agents on the ecology of the human intestinal microflora. AB - The most common and significant cause of disturbances in the normal intestinal microflora is the administration of antimicrobial agents. The microflora can be influenced by antimicrobial agents because of incomplete absorption of any orally administered antimicrobial agent, secretion of an antimicrobial agent in the bile, or secretion from the intestinal mucosa. Administration of these agents may seriously disturb the balance of the normal intestinal microflora. This disturbance can cause bacterial overgrowth and emergence of resistant microorganisms which may lead to serious infections and also encourage transfer of resistance factors among bacteria. The ecological effects of penicillins, cephalosporins, monobactams, carbapenems, macrolides, clindamycin, tetracyclines, nitroimidazoles and quinolones on the human intestinal microflora are presented in this review article. PMID- 8212507 TI - An evaluation of methods to assess the effect of antimicrobial residues on the human gut flora. AB - 1. Barrier effect. Relevant models should include an anaerobic dominant flora that antagonizes minor bacterial populations such as drug resistant E. coli. 2. Anaerobes vs. aerobes. Aerobe counts are more precise and much less time consuming than anaerobe counts. Minor populations of drug resistant aerobes are sensitive markers of the ecosystem balance, and are directly relevant to the potential risk of antimicrobial residues. 3. MIC vs. plate counts. The determination of minimum inhibitory concentrations (MIC) of selected clones in time consuming, does not detect subdominant resistance (less than 1%), and the MIC shift is difficult to test statistically. In contrast, direct counts of bacteria on drug supplemented media allows a rapid measure of minor resistant populations. 4. STATISTICS: Most published designs do not include adequate statistical evaluation. This is critical for trials made in conventional humans and animals, where data are highly variable. 5. Human trials: The lowest concentration of antibiotic tested in human volunteers (2 mg oxytetracycline/d for 7d in 6 subjects) significantly increased the proportion of resistant fecal enterobacteria (P = 0.05). However, the huge day-to-day and interindividual variations of human floras make this evidence rather weak. 6. Gnotobiotic mice inoculated with human flora are living isolated models in which the effect of any antimicrobial on the human gut flora can be tested. This in vivo model does include the barrier effect of dominant anaerobes. Interindividual and day-to-day variations of bacterial populations are lower in those mice than in humans. 7. Most resistant enterobacteria in the human gut of untreated people come from bacterial contamination of raw foods. The relative contribution of residues in selecting antibiotic resistance seems to be low when compared to bacterial contamination. PMID- 8212508 TI - Allergy to antimicrobial residues in food: assessment of the risk to man. AB - Meat and other dietary products from food animals and farmed fish in the West may contain residues of many antibiotics and antibacterial agents, or haptenised macromolecules, e.g. penicilloylated proteins. General surveys have shown a low incidence of detectable residues in most products (up to 0.5-2%). A notable proportion of the general population has true allergic sensitivity to these substances (up to 7-10% to "penicillin") due to prior medical treatment. However, cases of proven allergy to such substances in food are extremely rare, based on clinical and laboratory proof of an immunological reaction, whereas there are less well substantiated reports blaming antibiotics in up to 50% of cases of chronic urticaria. Consideration of nature of haptenisation by antimicrobial substances, of the inefficiency of the oral route for immunisation, and of the transient and unrepeatable nature of most examples of food-related reactions all suggest that allergy to antimicrobial residues in the diet is exceedingly rare. PMID- 8212509 TI - Mechanisms of antimicrobial resistance and implications for epidemiology. AB - The development of antibacterial agents has provided a means of treating bacterial diseases which were, previously, often fatal in both man and animal and thus represents one of the major advances of the 20th century. However, the efficacy of these agents is increasingly being compromised by the development of bacterial resistance to the drugs currently available for therapeutic use. Bacterial resistance can be combated in two ways. New drugs to which bacteria are susceptible can be developed and policies to contain the development and spread of resistance can be implemented. Both strategies require an understanding of the mechanisms of drug resistance, its epidemiology and the role of environmental factors in promoting resistance. Over the past thirty years our knowledge of bacterial resistance has increased dramatically mainly due to new technology that has become available. Bacteria are able to resist antibacterials by a variety of mechanisms: for example, altering the target to decrease susceptibility to the antibacterial, inactivating or destroying the drug, reducing drug transport into the cell or metabolic bypass. These drug resistance determinants are mediated via one of two distinct genetic mechanisms, a mutation in the bacterial chromosome or by a transmissible element; either a plasmid or a transposon. Significant differences exist between these two types of drug resistance as transmissible resistance, which is mainly plasmid-mediated, permits intraspecies and even interspecies transfer to occur. In contrast, chromosomal resistance can only be passed on to progeny. Transmissible antibacterial resistance is the major cause of concern as it can lead to the rapid spread of antibacterial resistance and has proven difficult, if not impossible, to eradicate. Furthermore, plasmids and transposons can code for multiple antibiotic resistance as well as virulence genes. Antibacterials for which transferable resistance has been identified include most commonly used antibacterials such as beta-lactams, aminoglycosides, macrolides, sulphonamides, tetracyclines, chloramphenicol and trimethoprim. One notable exception is the 4-quinolones for which plasmid-mediated resistance has yet to be identified. PMID- 8212510 TI - Evolution of resistance in microorganisms of human origin. AB - Resistance to antimicrobials in bacteria results from either evolution of "new" DNA or from variation in existing DNA. Evidence suggests that new DNA did not originate since the use of antibiotics in medicine, but evolved long ago in soil bacteria. This evidence is based on functional and structural homologies of resistance proteins in human pathogens, and resistance proteins or physiological proteins of soil bacteria. Variation in existing DNA has been shown to comprise variations in structural or regulatory genes of the normal chromosome or mutations in already existing plasmid-mediated resistance genes modifying the resistance phenotype. The success of R-determinants in human pathogens was due to their horizontal spread by transformation, transduction and conjugation. Furthermore, transposition has enabled bacteria to efficiently distribute R determinants between independent DNA-molecules. Since the genetic processes involved in the development of resistance are rare events, the selective pressure exerted by antibiotics has significantly contributed to the overall evolutionary picture. With few exceptions, experimental data about the role of antibiotic usage outside human medicine with respect to the resistance problem in human pathogens are missing. Epidemiological data about the occurrence of resistance in human pathogens seem to indicate that the major contributing factor to the problem we face today was the extensive use of antibiotics in medicine itself. PMID- 8212511 TI - Medical and veterinary use of antimicrobial agents: implications for public health. A clinician's view on antimicrobial resistance. AB - It is often proposed that the indiscriminate use of antimicrobial agents in the veterinary field leads to increased resistance in bacteria pathogenic to humans. Although for human medicine there is some potential danger behind the use of antimicrobial agents in animals, very few species (such as Staphylococci, Salmonella, Escherichia coli, Yersinia and Campylobacter) isolated in animals, which are also pathogenic to man, have been mentioned in the literature. The present paper analyzes the areas and bacteria where the clinician faces problems in the treatment of infection in man. PMID- 8212512 TI - Monitoring of resistant organisms in man and identification of their origin. AB - Information on the epidemiology of bacterial resistance is fragmentary despite an enormous number of publications since the introduction of antibiotics to human medicine, and remains a field of speculation mixed and influenced by fear of the total collapse of antimicrobial chemotherapy by development of resistance (for review see Wiedemann et al., 1986). Bacteria have evolved mechanisms to withstand the attack of antibiotics and, in parallel, mechanisms for the spread of these characters to other bacteria by means of exchange of genetic information. However the development of resistance cannot be generalized. Staphylococcus aureus gained penicillin resistance within a few years after the introduction of this drug, while Streptococcus pyogenes remains 100% susceptible to penicillin, despite of the long use of penicillins in huge quantities. Thus any statement about the development and epidemiology of resistance has to be addressed specifically to a drug, a bacterial species, and a location. Until now there is no identifiable general trend, which would allow us to deduce a general picture or a future development from a limited database. In this paper long term multicentre studies are presented to demonstrate the area of concern for the treatment of human infections. In this context it is of specific interest to try and trace the origin of bacteria which cause infections in humans. PMID- 8212513 TI - Responsible use of antimicrobials in veterinary medicine: perspectives in France. AB - In France a survey of the use of antimicrobials in veterinary medicine was set up in connection with the Committee for the Marketing Authorization of Veterinary Medicinal Products. This survey has emphasized the importance of antimicrobials in veterinary medicine and the reality of antibiotic resistance in both man and animals. Certain epidemiological data tend to demonstrate that the use of antibiotics in animals increases the risk of antibiotic resistance in man, through selection in animals of resistant pathogenic bacteria or of a non pathogenic resistant bacteria carrying resistance plasmids. Four proposals are put forward for the control of these different risks: reserve certain antibiotics (life-saving antibiotics) for human medicine, conform to a code of good practices for antibiotic use in animals, strengthen and connect up existing networks for the epidemiosurveillance of antibiotic resistance, provide for studies on the ecological impact of antibiotics in the registration dossiers for veterinary medicinal products. These evolutive measures, based on scientific progress in microbiology, epidemiology and clinical studies should respond satisfactorily to the expectations of all concerned. PMID- 8212514 TI - A veterinary antibiotic policy: a personal view on the perspectives in The Netherlands. AB - To reach a more adequate and responsible use of antibiotics in veterinary medicine a broad approach is required. The growing interest in the optimum use of antibiotics in veterinary medicine is stimulated by awareness of the necessity to prevent the emergence of resistance and the spread of resistant bacteria. This is a matter of primary importance to safeguard the efficacy of antibiotic therapy in animals now and in the future, but will also minimise possible public health risks. As resistance develops in rough relation to antibiotic use, the best way to minimise emergence of resistance, without interfering with optimal veterinary care, is to rationalize the use of antibiotics by, or under responsibility of, a veterinary surgeon. A second further improvement can be reached by developing a veterinary antibiotic policy to prevent emergence and spread of resistance as much as possible. Measures that must be taken in combination are: 1. Establishing a policy for the use of antibiotics jointly by veterinary practitioners and experts resulting in a formulary. 2. Systemic registration and analysis of patterns of bacterial resistance (not only of pathogens but of faecal flora as well) and the use (qualitative and quantitative) of antibiotics in veterinary medicine. 3. Regular feedback of these data to the veterinary practitioners and consultation about the efficacy of the formulary guidelines in daily practise. 4. Systemic monitoring and evaluation the impact of the antibiotic policy and, if indicated, updating of the formulary. 5. Continuous education of veterinary surgeons about infectious diseases and antimicrobial therapy and development of a veterinary audit system. The first step to rationalize the veterinary use of antibiotics was taken by publishing a veterinary antibiotic formulary in 1987, compiled by a group of experts. Despite the fact that this was a pure top down approach and bottom up input from veterinary practitioners was lacking, this first formulary was very well received. However the impact of this formulary on the veterinary use of antibiotics and prevalence of resistance has not been evaluated at this moment. Until now regular and nationwide systemic monitoring of resistance and registration of veterinary use of antibiotics is not practically feasible in the Netherlands. A new formulary, based on a veterinary antibiotic will be published by the end of 1992. However, to be able to evaluate the impact of this policy on the prevalence of resistance and, if necessary, to adapt the policy the development of facilities for resistance epidemiology is urgently needed. PMID- 8212515 TI - Bacterial resistance monitoring of salmonellas isolated from animals, national experience of surveillance schemes in the United Kingdom. AB - Antimicrobial resistance has been monitored in salmonellas isolated from animals in England and Wales since 1970. The current trends are indicated by comparing the results for the years 1981, 1989 and 1990. Seventy-six per cent of all salmonella isolations are still sensitive to all 16 antimicrobials used for testing. Most antimicrobial resistance is encountered in bovine isolations of Salmonella typhimurium especially phage type DT204C. This phage type, which was initially resistant to at least seven antimicrobials, has however become more susceptible in recent years. Ninety-eight per cent of S. dublin strains from cattle are still sensitive to all the antimicrobials used for testing. Although the number of porcine salmonella isolations is small, many show antimicrobial resistance especially to tetracyclines. A large increase in the number of salmonellas isolated from poultry has occurred in recent years and 75% of these strains are sensitive to all the antibiotics used for testing. Although there has been a slight decrease in the percentage of S. enteritidis strains showing susceptibility 87% of isolations are still sensitive. The emergence of resistance to the newer antimicrobials trimethoprim, apramycin and fluorquinolones has been studied and data presented. The results are discussed with regards to the choice of techniques, bacteria monitored and future surveillance programmes in relation to the veterinary use of antimicrobials. PMID- 8212516 TI - Bacterial resistance monitoring in animals: the French national experiences of surveillance schemes. AB - In France, bacterial resistance monitoring in animals is based on a national network of local veterinary laboratories organised by CNEVA following two methodologies. As part of the epidemiological surveillance of Salmonella, LCHA in Paris has been receiving since 1969 most of the strains isolated from animals (sick and healthy carriers) but also from food, feed and environment. For many years sensitivity tests have been carried out on strains collected: animal ones, mainly from cattle and poultry, show multiple antibiotic resistance more frequently than those of food or environment. Taking into account of the importance of antibiotic resistance in E. coli and Salmonella isolated from sick calves, LPB in Lyon has set up since 1982 a national system for collecting and analysing antimicrobial sensitivity patterns of main bovine pathogens determined routinely by local veterinary laboratories. In order to ensure comparability and coherency of data from different laboratories it was necessary to introduce standard techniques and reference reagents. The major bacterial species being tested concern enteric, respiratory and mammary flora. This network is useful to detect new resistances. The resistant strains collected are useful to carry out studies on the mechanism of resistance and the efficacy of new molecules. Results constitute the basis of a real predictive epidemiology necessary to lay down a policy for rational use of antimicrobials in animal breeding and veterinary medicine. PMID- 8212517 TI - The role of the pharmaceutical animal health industry in post-marketing surveillance of resistance. AB - The pharmaceutical animal health industry must be committed to the total life cycle of products, i.e. during both the pre- and post-marketing period. Support of antibacterial agents during the postmarketing period is not restricted to maintaining a well-established distribution and promotion system. Care has to be taken continuously to maintain and/or improve the quality, safety (for user, target animal and environment) and clinical efficacy. The pharmaceutical industry contributes to this by: 1. Introducing antibacterials in different animal species for the most effective disease condition only and by ensuring the veterinary profession is informed about relevant findings on: a. the mechanism of action; b. pharmacodynamic properties; c. pharmacokinetic properties (plasma, target tissue); d. clinical efficacy data and in vitro sensitivity data; e. valid species-specific MIC breakpoints; f. precise dose and treatment regime. 2. Updating on a regular basis on: a. new findings on the mechanism of action (in vitro and in vivo); b. the optimal use program in the light of changes in animal husbandry, farm management and epidemiology on national and international level; c. adjustment of species-specific MIC breakpoints when necessary. 3. Providing continuous information in collaboration with animal health laboratories about: a. clinical field surveillance for efficacy (national, international); b. in vitro sensitivity/resistance surveillance (national, international); c. use of in vitro data to support prediction of in vivo efficacy. Surveillance of resistance, in vitro, is therefore part of a package of information needed on a routine basis by the pharmaceutical industry to allow the best possible use of antibacterials and to minimize induction of resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212518 TI - The proper use and benefits of veterinary antimicrobial agents in practice in cattle. AB - A rational basis for the therapeutic and prophylactic use of antimicrobials is discussed. Different approaches are needed to deal with the individual animal, group or herd disease problem. Improved antibiotic preparations are needed to enhance the efficacy of treatment and minimise suffering and lost production. PMID- 8212519 TI - The proper use and benefits of veterinary antimicrobial agents in swine practice. AB - There are three main reasons for using antimicrobial agents in pig production: animal welfare, carcase quality and economics. The need to treat sick animals and to mitigate the effects of infection is of paramount humanitarian importance. The reduction of the pathological effects of infection is an essential aspect of carcase quality and of possible value in the control of potential zoonoses. It is beyond dispute that the judicious use of antimicrobial agents improves growth efficiency. In addition there are economic benefits to be gained from the control of infection in terms of improved carcase quality and reduced mortality. When antimicrobial agents are used, careful consideration must be given to their choice. An understanding of the disease complexes of pig herds, of pharmacokinetics and of methods of administration is necessary to achieve safe and cost-effective medication. Bacterial resistance to antimicrobial agents in pig production is of importance only in special circumstances where eradication of a disease is being attempted. Veterinarians specialising in pig production are concerned that there is a climate of restriction of use and availability of suitable agents which could jeopardize animal health and welfare. PMID- 8212520 TI - Immunohistological observations on pulmonary tissues from dogs infected with Dirofilaria immitis. AB - Pulmonary tissues from non-infected dogs, naturally Dirofilaria immitis-infected dogs and experimentally infected puppies, selectively necropsied after infection, were assessed using peroxidase-antiperoxidase (PAP) staining technology. Sequential sections of pulmonary tissue were PAP stained with anti-fresh D. immitis serum, anti-paraffin processed D. immitis serum, anti-dog immunoglobulin (IgG, IgG Fc, IgM) sera and anti-dog complement (C3) serum, and examined for antibody, complement and for D. immitis antigen. The extent of alveolar septal thickening was positively correlated with infection status. Cellular infiltration was most evident surrounding obstructed areas where D. immitis were in situ. Antigenic material (microfilariae, eggs, fragmented filariae) labelled by PAP was identified in the pulmonary arteries, alveolar capillaries and alveolar septa. Deposits of complement and IgG, presumably associated with immune complex formation, were also observed in some of the infected dogs. Identification of antigen, antibodies and complement associated with alveolar septal pathology suggested that immune mechanisms were active in its development. PMID- 8212521 TI - The disposition of carbenicillin in blood, other body fluids and tissues of buffalo calves (Bubalus bubalis). PMID- 8212523 TI - The uptake of fenbendazole by cattle and buffalo following long-term low-level administration in urea-molasses blocks. AB - Fenbendazole (Panacur bolus, Hoechst India Ltd) was incorporated at a rate of 0.5 g/kg into urea-molasses blocks made by two different processes. The concentration of the drug in blocks and its bioavailability were measured using plasma oxfendazole as marker. The recovery of the drug in blocks made by a warm process was 68% and the plasma oxfendazole concentration remained fairly stable at 0.2 and 0.12 microgram/ml from day 6 of feeding in cattle and buffalo, respectively. The drug seemed to be inactivated in blocks made by a hot process, with reduced bioavailability. A low and sustained plasma concentration of the active metabolite of the drug could be maintained by self-medication using urea-molasses blocks as fenbendazole carrier. PMID- 8212522 TI - The pharmacokinetics of primaquine in calves after subcutaneous and intravenous administration. AB - The pharmacokinetics of primaquine was studied in calves of 180-300 kg live weight. Primaquine was injected at 0.29 mg/kg (0.51 mg/kg as primaquine diphosphate) intravenously (IV) or subcutaneously (SC) and the plasma concentrations of primaquine and its metabolite carboxyprimaquine were determined by high-performance liquid chromatography. The extrapolated concentration of primaquine at zero time after IV administration was 0.50 +/- 0.48 microgram/ml (mean +/- SD) which decreased with an elimination half-life of 0.16 +/- 0.07 h. Primaquine was rapidly converted to carboxyprimaquine after either route of administration. The peak concentration of carboxyprimaquine was 0.50 +/- 0.08 microgram/ml at 1.67 +/- 0.15 h after IV administration. The corresponding value was 0.47 +/- 0.07 micrograms/ml at 5.05 +/- 1.20 h after SC administration. The elimination half-lives of carboxyprimaquine after IV and SC administration were 15.06 +/- 0.99 and 12.26 +/- 3.06 h, respectively. The areas under the concentration-time curve for carboxyprimaquine were similar following either IV or SC administration of primaquine; the values were 11.85 +/- 2.62 micrograms.h/ml after the former and 10.95 +/- 2.65 micrograms.h/ml after the latter. The mean area under the concentration-time curve for primaquine was less than 0.1 micrograms.h/ml after either route of administration. PMID- 8212524 TI - Oscillatory measurements, blood gas analysis and clinical observations after intravenous clenbuterol administration in healthy and acutely pneumonic calves. AB - The effects of clenbuterol (Ventipulmin, Boehringer Ingelheim) on respiratory functions were investigated in 6 calves aged 4-6 weeks prior to and after experimental infection with Pasteurella haemolytica A1. On days 1-3 (prior to infection) and on days 7-9 (after infection), blood gas analysis, monofrequency forced oscillation techniques and clinical examinations (heart rate, respiratory rate) were conducted for 135 min after the intravenous administration of clenbuterol (0.8 microgram/kg body weight). In healthy calves prior to Pasteurella infection, intravenous administration of clenbuterol induced a mild tachycardia and a reduction in the mean oscillatory respiratory resistance. Using the same dose of clenbuterol in diseased calves after infection, the statistically significant reduction in oscillatory respiratory resistance was more impressive and it was accompanied by a significant increase in the oxygen pressure of the arterialized blood. Heart rate and respiratory rate did not change significantly after the administration of clenbuterol in infected calves. PMID- 8212525 TI - Genetic control of cellular infection by subgroups A and C RNA tumour viruses in guinea fowl. AB - An investigation was carried out in guinea fowl to determine their susceptibility to infection by Rous sarcoma viruses of subgroups A and C. A standard dose of each subgroup virus was inoculated into 14-day-old embryos via the chorioallantoic membrane (CAM). On the 10th day after inoculation, 50% of the embryonic chorioallantoic membranes were harvested to assess their infection status (CAM(+) or (-)), while the rest were allowed to hatch. The hatchabilities of the embryos inoculated with subgroups A and C were about 50% and 57%, respectively. The relative sensitivities of guinea fowl to infection by viruses of subgroups A and C were observed to be 0.220 and 0.003, respectively, as compared to chickens (1.00). Mortality due to subgroup A virus-induced liver tumours (LT) was 54% and four phenotypic subclasses, namely CAM(+) LT(+), CAM(+) LT(-), CAM(-) LT(+) and CAM(-) LT(-), were observed in guinea fowl as in chickens. However, a higher incidence (31%) of conversely associated phenotypes, i.e. CAM(+) LT(-) and CAM(-) LT(+), were observed in guinea fowl. Mortality caused by subgroup A virus-induced liver tumours was first observed in inoculated guinea fowl keets during the 3rd week after hatching, and 93% of the mortality occurred within 6 weeks. The peak mortality occurred in the 4th week after hatching. The target organs for transformation were considered to be the liver and spleen because of the equal incidence of tumours in these organs. Males and females were equally likely to die from liver tumours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212526 TI - Potentiation of the in vitro activity of some antimicrobial agents against selected gram-negative bacteria by EDTA-tromethamine. AB - The in vitro synergistic effects of combinations of EDTA-tromethamine and six antimicrobial agents (ampicillin, chloramphenicol, oxytetracycline, streptomycin, nalidixic acid and sulphadimethoxine) on clinically isolated strains of Pseudomonas aeruginosa, Proteus mirabilis and Escherichia coli were investigated. The antibacterial activity was assessed from the minimal inhibitory concentration for the antibiotics alone or in combination with EDTA-tromethamine. EDTA tromethamine potentiated the antibacterial activity of ampicillin, chloramphenicol, oxytetracycline and streptomycin up to four-fold. There were no significant or consistent synergistic effects with nalidixic acid or sulphadimethoxine. PMID- 8212527 TI - Changes in serum C-reactive protein levels in dogs with various disorders and surgical traumas. AB - The serum levels of C-reactive protein (CRP) produced as an inflammatory response in dogs with various disorders and surgical traumas were measured by enzyme linked immunoabsorbent assay and slide reversed passive latex agglutination test (RPLA). The CRP levels were greatly increased 1-2 days after surgery in most of the dogs (n = 29) subjected to surgery. These levels had markedly decreased by the time the sutures were removed. In dogs with various disorders (n = 58), the serum CRP levels at first diagnosis were high in infectious diseases. In dogs from which paired serum samples were examined, the serum CRP usually showed a decrease with improvement in the condition (n = 11) or a terminal increase (n = 4) but, conversely, some showed an increase with improvement in the condition (n = 3). PMID- 8212528 TI - The association between antibody titres against Campylobacter fetus and reproductive efficiency in dairy cattle. AB - The relationship between the antibody titres against Campylobacter fetus and various indices of reproductive efficiency was studied in a cross-sectional study of 178 dairy cows from three California Dairy Herd Improvement Association herds. Blood samples were collected from the lactating cows during December 1986. Enzyme linked immunosorbent assays were used to determine the antibody titres of the cow against Campylobacter fetus, Haemophilus somnus and Leptospira hardjo and were classified as either negative or positive. The status of a cow as either negative or positive against Campylobacter fetus and Haemophilus somnus represents serological evidence of natural exposure to the corresponding bacterial agents. However, the status against Leptospira hardjo was assumed to reflect a vaccinal titre since all the cows studied had been routinely vaccinated against this organism in September 1986. The data on demographic and reproductive parameters pertained only to the current lactation of the cows and were obtained from Dairy Herd Improvement Association individual cow records of December 1986. Five indices of reproductive efficiency were used, namely the recent calving interval, the calving-to-conception interval, the calving-to-last-service interval, the number of services per conception, and the number of services since last calving. The serological status against Haemophilus somnus, Leptospira hardjo and other covariates suggested by the results of previous studies were included in modelling the relationships of interest. Stepwise multiple linear regression analyses were carried out to study the adjusted relationship of Campylobacter fetus with each measure of reproductive efficiency. Multivariate analyses revealed that the adjusted relationship for Campylobacter fetus with all five measures of reproductive efficiency was non-significant (p > 0.05). Among the covariates, Leptospira hardjo had a strong and independent relationship with recent calving interval, the unstandardized partial regression coefficient being 0.77. The possible biological mechanisms of these associations are discussed. PMID- 8212530 TI - Diagnostic tools for differentiating between pleural mesothelioma and lung adenocarcinoma in paraffin embedded tissue. Part I: Immunohistochemical findings. AB - Specimens of 27 histologically definite mesotheliomas and 34 proven adenocarcinomas were examined with a panel of 14 antibodies: pan-epithelial antibody Lu-5, anti-keratin-18, anti-keratin-7, Ber-EP4, anti-Leu-M1, HEA-125, anti-carcino-embryonic antigen (CEA), anti-blood group-related antigens (anti-BGR A, B, H), B72.3, anti-placental alkaline phosphatase (PLAP), anti-vimentin and BMA-120 used to determine their value in the differentiation between pleural mesothelioma and lung adenocarcinoma. Lu-5, anti-cytokeratin-7 and -18, B 72.3 and PLAP reacted in a high percentage of cases with both mesothelioma and adenocarcinoma. Anti-CEA and anti-Leu-M1 did not react with any of the 27 mesotheliomas tested but showed a reaction in 75% (anti-CEA) and 66% (anti-Leu M1) of the lung adenocarcinomas. Seventeen percent of the adenocarcinomas and 96% of the mesotheliomas showed a positive reaction with anti-vimentin. Ber-EP4 was demonstrated in all lung adenocarcinomas, but only in 2 mesotheliomas in a focal manner (7%). HEA-125 and anti-BGR A, B, H reacted with 83% (HEA-125) and 75% (anti-BGR A, B, H) of the lung adenocarcinomas. The statistical parameters, sensitivity and efficiency were estimated and a normogram for judging the diagnostic power of a single antibody for the differential diagnosis of mesothelioma versus adenocarcinoma was developed. According to this, Ber-EP4, HEA 125, anti-BGR A, B, H and anti-CEA were, in descending order, the most powerful discriminatory antibodies. PMID- 8212531 TI - Histochemical and biochemical determination of calcium in salivary glands with particular reference to chronic submandibular sialadenitis. AB - Although salivary calcification is relatively common, little is known about the localization and content of the calcium of normal and diseased human salivary glands. We investigated this in chronic submandibular sialadenitis with a variable mixture of relatively normal and extremely atrophic parenchyma and in normal submandibular, parotid and palatal glands. Calcium was localized histochemically in mucous acinar cells of submandibular and palatal glands at moderate to high levels, in serous acinar cells of submandibular and parotid glands at low to moderate or occasionally high levels, in mucous ductal cells at moderate to high levels, and in extremely atrophic parenchyma at low levels or not at all. Calcium was determined biochemically at relatively high levels in the different glands in the order palatal, submandibular, sialadenitis and parotid. However, the differences were small. The results indicate that most salivary calcium is associated with secretory granules; this is the likely source of the calcium involved in salivary calcification. PMID- 8212532 TI - In vitro study of the bronchial mucosa during Pseudomonas aeruginosa infection. AB - The route of bacterial infection of the lower respiratory tract is generally one of descent subsequent to colonisation of the oral and oropharyngeal mucosa. The interaction between Pseudomonas aeruginosa (wild type) and the bronchial epithelium was studied in bronchial mucosal probes cultured in tissue culture medium. It was possible to demonstrate that, even after loss of the mucus layer, adherence between the bacteria and the bronchial epithelium does not take place if ciliary function remains intact. Only after mechanical destruction of the bronchial epithelium, in proximity to squamous metaplasia or after loss or malfunction of the cilia of the bronchial epithelial cells was adhesion between bacteria and bronchial epithelial cells or basement membrane demonstrated by electron microscopy. After loss of the cilia following adenovirus-infection, adhesion between P. aeruginosa and the bronchial epithelial cells was visible. These results indicate that ciliary function must be of crucial significance in bacterial epithelial colonisation. PMID- 8212529 TI - The hepatic extracellular matrix. I. Components and distribution in normal liver. AB - The unique nature of the hepatic extracellular matrix (ECM) is predicated by the special configuration of the space of Disse. Whereas other epithelial organs have two basement membranes (BM) and a substantial ECM interposed between endothelial and epithelial cells, the liver lobule has no BM and only an attenuated ECM, consisting mostly of fibronectin, some collagen type I, and minor quantities of types III, IV, V, and VI. This configuration, together with the abundant fenestrations and gaps of the sinusoidal endothelial cells, seems ideally suited to facilitate the rapid bidirectional exchange of macromolecules normally taking place between plasma and hepatocytes. During organogenesis, the liver anlage is vascularized by continuous capillaries with BM, but by day 13.5 of development (in the rat) the vessels in the immediate proximity of hepatocytes become fenestrated, lacking specialized junctions and BM, suggesting that the hepatocytes produce signals capable of modulating the endothelial phenotype. In regeneration, hepatocyte proliferation precedes vascular proliferation resulting in the formation of hepatocyte clusters that, temporarily, lack sinusoids. Eventually, vascular proliferation follows and the normal hepatocyte-vascular relationships are restored. During this period laminin synthesis by Ito cells is prominent. As soon as hepatocytes become stable, secretion of the sinusoid phenotype-maintaining factors resumes and laminin synthesis and secretion terminates. The interplay between extracellular matrix and liver cells is essential for normal homeostasis and its modification results in deranged hepatic function. PMID- 8212533 TI - Altered intestinal development after jejunal ligation in fetal sheep. AB - Experimental obstruction of the fetal small intestine resulted in massive hypertrophy of the segment proximal to the site of obstruction. Villus morphology was grossly abnormal. Enterocytes developed many irregular features, most notably cytoplasmic extensions (pseudopods, or blebs) from their apical surface. Distal to the site of obstruction, morphological anomalies which resembled those seen after experimental oesophageal ligation were found. These included delayed disappearance of the apical endocytic network, disrupted or absent microvilli, glycogen accumulation and inappropriate cell extrusion. Proximal to the obstruction, where stasis of swallowed fluid occurs, distension and abnormal intestinal development ensues. Distal to the obstruction where the intestine develops in the absence of swallowed fluid, development is also abnormal. The anomalies resemble those noted after oesophageal ligation in utero, and possibly are the results of reduced cellular nutrition. These results suggest that fetal ingestion provides the developing gastrointestinal tract with an important stimulus for normal growth. PMID- 8212534 TI - Immunocytochemical detection of DNA topoisomerase type II in primary breast carcinomas: correlation with clinico-pathological features. AB - DNA topoisomerase type II (DT-II) is a major component of interphase nuclear matrix fractions, present in S-phase of the cell cycle. A series of 80 carcinomatous breast surgical samples was evaluated by immunohistochemistry, using a polyclonal antibody in a comparison with Ki-67 antiserum. A correlation with clinico-pathological data was also performed. Infiltrating ductal and lobular carcinomas constantly express DT-II with varying intensity of nuclear staining; a similar immunohistochemical pattern is observed with Ki-67. A frequent co-expression of DT-II and Ki-67 is encountered with double immunostaining; accordingly to these data, a linear relationship is evident when linear regression is employed. In addition, significant relationships between DT II values and tumour size, histological grade and node involvement are shown, while an inverse correlation is appreciable between DT-II and oestrogen receptors and progesterone receptors. DT-II may be considered to be an additional operational marker for the proliferating fraction of cells in breast carcinomas. PMID- 8212536 TI - Primary rhabdomyosarcoma of the iliac bone in an adult: a case mimicking fibrosarcoma. AB - Primary rhabdomyosarcoma of bone is exceedingly rare. We present a case of rhabdomyosarcoma of the iliac bone in a 32-year-old male. Histologically, the tumour consisted mainly of a uniform proliferation of elongated spindle cells arranged in a herring bone pattern, simulating fibrosarcoma. Focally there was a conventional embryonal pattern with scattered rhabdomyoblasts possessing an eosinophilic cytoplasm. Immunohistochemical studies disclosed expression of muscle markers such as desmin and muscle-specific actin, in both the embryonal and spindle-cell areas and myoglobin only in the embryonal areas. Such histological features are unusual for classical embryonal rhabdomyosarcoma. The anatomical site and age of the patient are also atypical. PMID- 8212537 TI - The evidence of human herpesvirus 6 infection in the lymph nodes of Hodgkin's disease. AB - Human herpesvirus 6 (HHV-6), the causative agent of exanthem subitum, has been implicated in other diseases. Recently HHV-6-specific sequences have been detected by Southern blot analysis and polymerase chain reaction in the lymph nodes of three patients with Hodgkin's disease. The pathological localization of HHV-6, however, is still unknown. In order to study the pathological role of HHV 6 in Hodgkin's disease, we investigated, by immunohistochemical and molecular methods, two lymph node biopsies taken from a 7-year-old boy with Hodgkin's disease during the course of disease evolution. Although the histopathological findings of the first biopsy differed from those of the second, HHV-6 antigens and sequences could be detected in both lymph nodes by immunohistochemistry and in situ hybridization, respectively. HHV-6 was localized in macrophages, predominantly in lymphoid follicles, but not in Reed-Sternberg cells. Antibody titres to HHV-6 were consistent with reactivation of latency. Neither cytomegalovirus nor Epstein-Barr virus was present. Our data suggest a role for HHV-6 in the pathogenesis of Hodgkin's disease. PMID- 8212535 TI - Localization of epidermal growth factor/transforming growth factor-alpha receptor in the human gastric mucosa. An immunohistochemical and in situ hybridization study. AB - Current evidence indicates that epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) play a pivotal role in the maintenance of gastric mucosal integrity, via binding to a common cell-surface receptor (EGF/TGF-alpha receptor). We examined the distribution and cellular sites of synthesis of EGF/TGF-alpha receptor in normal human gastric mucosa by immunohistochemical and in situ hybridization techniques. Intense EGF/TGF-alpha receptor immunoreactivity was observed in the basal cytoplasm and along basolateral membranes of mucus neck cells, foveolar columnar cells, and surface epithelial cells facing the gastric lumen. Parietal cells and mucus-secreting pyloric gland cells displayed a distinct basolateral immunostaining, whereas the luminal membrane was unstained. Immunoreactivity was also noted in spindle-shaped cells of the lamina propria and in smooth muscle cells of the muscularis mucosae and muscularis propria. In situ hybridization revealed EGF/TGF-alpha receptor RNA transcripts in all cell types displaying positive immunoreaction. These results suggest a physiological role for EGF/TGF-alpha in the regulation of multiple gastric functions. The receptor distribution at the luminal aspect of the gastric mucosa provides the anatomical basis for a possible interaction of gastric juice EGF (or TGF-alpha) with cells of the mucosal surface, whereas the expression of EGF/TGF-alpha receptor in cells which are not in direct contact with the gastric lumen is consistent with blood mediated or paracrine/autocrine mechanisms of EGF/TGF-alpha action on these cells. PMID- 8212538 TI - Oncocytic hyperplasia in the human minor salivary glands: a post-mortem study. AB - Oncocytic hyperplasia in the human labial salivary glands was sought in a series of 217 post-mortem subjects. Oncocytic change occurred in 183 subjects and hyperplasia was found in 19 of those (the overall incidence being 8.8%), ranging in age from the third decade to the ninth. The sex distribution showed a significantly greater rate in males (16 of 139 males, 11.5%; 3 of 78 females, 3.8%). Oncocytic hyperplasia occurred in the duct system, and not in the acinar regions; it was frequently seen in the interlobular and intralobular ducts. Oncocytic hyperplasia was classified into four types; focal hyperplasia of the duct wall resulting in partial thickening of the duct wall; marked hyperplasia resulting in thickening of the duct wall, extending over half of the circumference; marked hyperplasia extending to the whole duct wall and intralobular adeno-tubular hyperplasia with or without cystic dilatation. About half of the subjects with oncocytic hyperplasia showed a few hyperplastic foci in one gland. The changes increased in severity in older subjects. PMID- 8212539 TI - Ultrastructural changes in glomerular epithelial cells in acute puromycin aminonucleoside nephrosis: a study by high-resolution scanning electron microscopy. AB - Ultrastructural changes in the podocytes were studied during the development of, and recovery from, acute puromycin aminonucleoside (PAN) nephrosis using high resolution scanning electron microscopy (hrSEM) and transmission electron microscopy (TEM). In the process of development of PAN nephrosis, four types of early structural changes were observed before total loss of foot processes: formation of cytoplasmic blebs, masking of filtration clefts, flattening of foot processes, and retraction of foot processes. The masking of filtration clefts visualized by hrSEM corresponded to the multiplication of slit diaphragms and adhesion of foot processes in the TEM findings, and preceded retraction of the foot processes. Changes of podocyte configuration were produced. Recovery from this change of podocyte configuration began as islands of podocyte interdigitation, and was proceeded by expansion of the islands. During recovery, the primary processes were re-established either by retraction or perforation of the thin cytoplasm after the formation of foot processes. We conclude that loss of foot processes begins with the masking of filtration clefts. Recovery from the change in podocyte configuration begins with the formation of new foot processes. PMID- 8212540 TI - Widening of capillary neck and alteration of extracellular matrix ultrastructure in diabetic rat glomerulus as revealed by computer morphometry and improved tissue processing. AB - Morphological and morphometric studies of glomeruli were carried out in streptozotocin-induced diabetic rats using improved tissue processing and computerized morphometry. Increased mesangial matrix, occupying the enlarged diabetic mesangium, contained an abundance of dark granular material in addition to the microfibrils which were usually found in the control glomeruli. In the diabetic glomeruli, the lamina densa was thick and heterogeneous showing a dense layer both on its epithelial and endothelial aspects, and the lamina rara externa contained more fibrils than in control rats. Detailed estimation of the absolute values of the various compartments of the diabetic glomeruli by using perfusion fixed materials and a computer-assisted digitizer revealed that the volume and surface area of the mesangium were increased more extensively than those of the capillary; the enlargement of the mesangial-capillary interface area was the most pronounced among the morphometric changes of the diabetic glomeruli; and that the moderate increase in capillary volume was associated with an increased radius. Our quantitative results showed that capillaries in the diabetic glomeruli had an extensively wider neck which may be the first sign of structural damage to the glomerular tuft. PMID- 8212541 TI - The extracellular matrix in sarcomatoid carcinomas of the breast. AB - The distribution of the main extracellular matrix components has been investigated immunohistochemically in four cases of breast sarcomatoid carcinomas. The histogenesis of these tumours is still unclear, but most evidence suggests that the sarcomatous component originates from mesenchymal conversion of carcinomatous cells. We found that carcinomatous portions of the tumours were associated with linear basement membrane-like deposition of laminin, type IV collagen and heparan sulphate proteoglycan that partially circumscribed the epithelial nests. The sarcomatous components produced an extracellular matrix immunoreactive to fibronectin, type I, III and VI collagens and tenascin. However, in two cases, in some sarcomatous areas, focal pericellular staining for antibodies to laminin and type IV collagen was seen. These results indicate that modifications observed in the double tissue component of these tumours involve not only the cell shape and the cytoskeleton, but also the components of the extracellular matrix. The significance of these findings and their relevance in the understanding of the phenotypic pattern changes of these biphasic tumours are discussed. PMID- 8212543 TI - The hepatic extracellular matrix. II. Ontogenesis, regeneration and cirrhosis. AB - The unique nature of the hepatic extracellular matrix (ECM) is predicted by the special configuration of the space of Disse. Whereas other epithelial organs have two basement membranes (BM) and a substantial ECM interposed between endothelial and epithelial cells, the liver lobule has no BM and only an attenuated ECM, consisting mostly of fibronectin (FN), some collagen type I, and minor quantities of types III, IV, V, and VI. This configuration, together with the abundant fenestrations and gaps of the sinusoidal endothelial cells, seems ideally suited to facilitate the rapid bidirectional exchange of macromolecules normally taking place between plasma and hepatocytes. During organogenesis, the liver anlage is vascularized by continuous capillaries with BM, but by day 13.5 of development (in the rat) the vessels in the immediate proximity of hepatocytes become fenestrated, lacking specialized junctions and BM, suggesting that the hepatocytes produce signals capable of modulating the endothelial phenotype. In regeneration, hepatocyte proliferation precedes vascular proliferation resulting in the formation of hepatocyte clusters that, temporarily, lack sinusoids. Eventually, vascular proliferation follows and the normal hepatocyte-vascular relationships are restored. During this period laminin synthesis by Ito cells is prominent. As soon as hepatocytes become stable, secretion of the sinusoid phenotype-maintaining factors resumes and laminin synthesis and secretion terminates. The interplay between extracellular matrix and liver cells is essential for normal homeostasis and its modification results in deranged hepatic function. PMID- 8212542 TI - Detection of Epstein-Barr virus in a case of undifferentiated nasopharyngeal carcinoma by in situ hybridization with digoxigenin-labelled PCR-generated probes. AB - A case of nasopharyngeal carcinoma is presented. Epstein-Barr viral genome was identified in the neoplastic cells by in situ hybridization with digoxigenin labelled polymerase chain reaction-generated probes. We report the development of this technique in paraffin-embedded sections and propose that such identification may prove valuable for the diagnosis of this tumour in routine material. PMID- 8212544 TI - Muscle regeneration after exercise-induced myoglobinuria: an electron microscopic study. AB - Muscle regeneration was studied by light and electron microscopy in a case of exercise-induced acute myoglobinuria in a young patient with carnitine-palmityl transferase deficiency. Various stages of regeneration existed in the foci of necrosis scattered throughout apparently normal muscle. Activated satellite cells, myoblasts and myotubes were found, some of them containing myofibrils. Among the cells accumulating in the necrotic fibres, some apparently contained surviving myonuclei. In some fibres of normal size, developing myofibrils were abundant. Surviving myonuclei may be of significance in the reaction of muscle cells after injury. PMID- 8212545 TI - Comparative study of histopathological alterations during intestinal infection of mice with pathogenic and non-pathogenic strains of Yersinia enterocolitica serotype O:8. AB - Yersinia enterocolitica is an invasive pathogen capable of causing a wide spectrum of gastrointestinal diseases in man. While there is a considerable body of data on the invasiveness of Y. enterocolitica in vitro, little is known about the events in vivo leading to the translocation of the bacteria from the intestinal lumen into the ileal tissue. There is no detailed ultrastructural information describing the course of infection of pathogenic Y. enterocolitica in comparison with an avirulent strain. We compared a virulent plasmid-bearing strain and an isogenic avirulent plasmid-free derivative strain of Y. enterocolitica serotype O:8 at the ultrastructural level, in the established model of murine yersiniosis. At 12 h post-inoculation we found no indications of an active invasion of the intestinal epithelium, although microcolonies of the pathogenic strain were detectable closely under the follicle-associated epithelium of the Peyer's patches. The plasmid-bearing strain of Y. enterocolitica affected the gut-associated lymphoid tissue which was destroyed 36 h post-infection. Unlike the pathogenic strain of Y. enterocolitica, the nonpathogenic plasmid-free strain caused no detectable morphological alterations in the ileal tissue by this time. Morphological evidence is provided that Yersinia does not invade the ileal epithelium in an active manner, as has been observed in vitro, but appears to be transported across the epithelial barrier by M-cells. PMID- 8212546 TI - Paramyxovirus fusion: a hypothesis for changes. PMID- 8212547 TI - A cosmid-based system for constructing mutants of herpes simplex virus type 1. AB - Cosmids containing large fragments of herpes simplex virus type 1 DNA were prepared using a vector that allows intact inserts to be excised using the restriction endonuclease PacI. Two independent sets (A and B) of five cosmids were identified whose inserts overlap and represent the entire viral genome, and set C was obtained by replacing two cosmids in set B. Each set gave rise to viral plaques when digested with PacI and transfected into cells in culture. Two cosmids common to sets B and C ostensibly contain one of the origins of viral DNA replication (oriL) in a region of overlap between inserts, but both actually consist of a minority of apparently intact (ori+L) forms and a majority of deleted (ori-L) forms. These sets yielded exclusively ori+L viral progeny. When either of these cosmids was replaced by a derivative comprising only ori-L forms, ori+L and ori-L progeny were obtained, and only ori-L progeny were produced when both were replaced. One cosmid in set A contains the oriL locus in a nonoverlapping region and lacks ori+L forms. This set generated only ori-L virus. Viral mutants with lesions in either or both of genes UL2 and UL44, which are not essential for growth in cell culture, were constructed using cosmids containing specifically introduced frameshift mutations. A mutant with a frameshift mutation in an essential gene (UL33) was isolated by transfecting a complementing cell line. These results indicate that a cosmid-based system will facilitate isolation of large numbers of defined viral mutants. PMID- 8212548 TI - Immunological characterization of the feline herpesvirus-1 glycoprotein B and analysis of its deduced amino acid sequence. AB - Feline herpesvirus 1 (FHV-1) is an important viral pathogen of cats. Like other alphaherpesviruses, FHV-1 contains a HSV-1 glycoprotein B (gB) homolog. In this study, monospecific antisera to HSV-1 gB reacted with three FHV-1 proteins (100, 64, and 58 kDa) present in virion lysates by immunoprecipitation and immunoblot analyses. Reduced stringency hybridization experiments using a HSV-1 gB probe localized the FHV-1 gB gene to a 9.6-kb Sa/l fragment in the unique long region of the genome. Northern blot analyses further localized the entire coding region within a 3.3-kb SacI fragment. The nucleotide sequence of this fragment was determined and two overlapping open reading frames (ORFs) encoding gB and ICP 18.5 were predicted. The amino acid sequence of the 2829 bp gB ORF was shown to have a high degree of homology with gB analogs of HSV-1, EHV-1, BHV-1, EHV-4, and especially PRV. Two unique characteristics of gB of FHV-1 were the unusually long signal sequence of 73 residues and two potential internal cleavage sites, RTRRS and RSRRS. An evolutionary tree based on gB homologs from 12 alphaherpesviruses suggests that feline herpesvirus-1 evolved along similar lines as the varicelloviruses, pseudorabies virus, bovine herpesvirus type 1, and equine herpesvirus types 1 and 4. The gB gene of FHV-1 was expressed in vaccinia virus (WR). This recombinant induced fairly high titers of virus neutralizing antibodies in rabbits. In Western blot analyses with potassium tartrate-purified virions, a 60-kDa polypeptide reacted with the rabbit antisera. PMID- 8212549 TI - Hepatitis delta virus cDNA monomer can be used in transfection experiments to initiate viral RNA replication. AB - The complementary DNA (cDNA) of hepatitis delta virus (HDV), constructed as tandem repeats under appropriate exogenous promoters, has been used to initiate viral replication in transfection experiments. Whether the structure of tandem repeats is essential has not yet been systematically examined. In this study, expression vectors containing only an HDV cDNA monomer, permutated at unique position of the genome, were shown still able to initiate viral replication. Furthermore, HDV cDNA monomer, separated from plasmid sequences by restriction enzyme digestion, also could be used to initiate viral RNA replication. The competence of HDV cDNA alone to direct viral RNA production suggested the presence of cryptic internal promoter-like elements. Such elements actually demonstrated by the chloramphenicol acetyltransferase assay. Therefore, HDV cDNA, in contrast to that of viroids, could be used to initiate viral RNA replication in monomeric form. This observation simplified the use of HDV cDNA for studying viral biology in transfection systems. PMID- 8212550 TI - Tyrosine sulfation of varicella-zoster virus envelope glycoprotein gpl. AB - Sulfation is a common post-translational modification of secreted and membrane proteins, with the sulfate attached to tyrosine residues or to glycan side chains. I have shown that varicella-zoster virus (VZV) envelope glycoproteins gpI, gpII, and gpIII can be labeled with [35S]sulfate. The predominant VZV glycoprotein, gpI, was shown to be sulfated on asparagine-linked glycans and on tyrosine. This is the first report of tyrosine sulfation of a viral envelope glycoprotein. Examination of the predicted amino acid sequences of gpI from the Dumas and CP-5262 VZV strains revealed the presence of a single consensus sequence for tyrosine sulfation of tyr88:IWPRNDYDGFLEN. Consensus sequences are also present in the homologues of gpI in herpes simplex type 1, herpes simplex type 2, and pseudorabies virus, suggesting that tyrosine sulfation may be a general post-translational modification of the neurotropic alphaherpesviruses. PMID- 8212551 TI - Sub-cellular localization of the 25-kDa protein encoded in the triple gene block of potato virus X. AB - The 25-kDa protein of potato virus X (PVX) is encoded by the 5' open reading frame of the overlapping triple gene block, has a GKS sequence motif characteristic of nucleotide binding proteins, and is thought to play a role in movement between cells. We have produced a polyclonal antibody to the 25-kDa protein to investigate its synthesis and intracellular location. On Western blots of infected tissue extracts this antibody detected a single major protein of the expected mobility, produced earlier than the viral coat protein in infected protoplasts and located predominantly in the 1000 g pellet fraction of infected cells. Immunogold labeling of thin sections of infected tissue revealed that the 25-kDa protein is associated with the cytoplasmic inclusion bodies characteristic of PVX infections, but not with the cell wall or plasmodesmata. Therefore, although mutational studies indicate a role for the 25-kDa protein in the cell to cell movement of viral infection it is unlikely to act in precisely the same manner as the other well-characterized movement proteins of tobacco mosaic and cowpea mosaic viruses. PMID- 8212552 TI - Cutaneous and mucosal human papillomavirus E4 proteins form intermediate filament like structures in epithelial cells. AB - Human papillomavirus (HPV) type 1 (HPV 1) is associated with benign cutaneous warts and HPV type 16 (HPV 16) with mucosal epithelial lesions that can progress to invasive carcinoma. The primary structure of the HPV E4 proteins is not highly conserved between types and their role in the viral life cycle is still unknown. A large panel of Simian virus 40 (SV40)-transformed human and monkey epithelial and fibroblast cell lines were infected with recombinant SV40/HPV1 E4 or SV40/HPV 16 E4 viruses and the expression of the viral proteins was analyzed by indirect immunofluorescence. Both HPV 1 and HPV 16 E4 proteins formed extensive and organized filamentous cytoplasmic networks that co-localized with the cytokeratin intermediate filaments. However, only HPV 16 E4 induced the collapse of the cytokeratin filaments. Furthermore, when both virus type E4 proteins were expressed within the same cell the collapse of the HPV 16 E4 filaments did not induced the collapse of the HPV 1 E4 network. Similar E4 filamentous structures were also observed in the cytoplasm of cells of the parabasal layer of an HPV 1 induced experimental wart. The HPV 16 E4 protein formed cytoplasmic networks in all SV40-transformed cell lines examined, but HPV 1 E4 only formed filamentous networks in human keratinocytes and in a monkey stomach epithelial cell line. In keratinocyte cells HPV 1 E4 species of 16, 17, 32, and 34 kDa were expressed, while in Cos-1 cells (in which no E4 networks are formed) only the 17 and 34 kDa polypeptides were found. The specific behavior of E4 proteins of cutaneous and mucosal HPVs expressed in cultured cells may suggest that these viral proteins have evolved to perform a similar function at different epithelial sites. PMID- 8212553 TI - Clonal expansion of hypermutated measles virus in a SSPE brain. AB - Nucleotide sequence analysis was carried out to study genes encoding the matrix (M) protein of measles virus (MV) from several regions of the brain of a case of subacute sclerosing panencephalitis. This analysis revealed the presence of MV with "wild-type" sequences as well as variants which had undergone at least five biased hypermutation events (U to C and A to G in the positive strand sequences). Despite the presence of MV variants with genes encoding the intact matrix protein open reading frame, M protein could not be detected in any of the brain regions. The distribution of virus variants was studied by cDNA cloning and sequence analysis and by in situ hybridization. The hypermutated viruses appeared to expand clonally throughout the brain of patient B. PMID- 8212554 TI - Mice transgenic for HTLV-I LTR-tax exhibit tax expression in bone, skeletal alterations, and high bone turnover. AB - HTLV-I infection can result in adult T cell leukemia with accompanying hypercalcemia and increased bone resorption. A viral etiology has also been invoked for Paget's disease, a disease of high bone turnover. Delineation of pathogenetic mechanisms of viral-associated bone diseases has been impeded by the complexity of viral and host factors. In order to consider the relationship of HTLV-I infection to skeletal changes we have evaluated the role of a single viral gene in mice transgenic for HTLV-I tax under the control of the viral promoter. Tax mice exhibited severe skeletal abnormalities characterized by high bone turnover, increases in osteoblast and osteoclast numbers and activity, and myelofibrosis. These changes were apparent as early as two months of age. Tax mRNA and protein were highly expressed in bone but not in bone marrow nor in any other tissues except, as previously reported, salivary gland and neurofibromas when they did develop. Within bone, tax protein was detected in only two cell types, mature osteoclasts and spindle-shaped cells within the endosteal myelofibrosis. These observations suggest that local expression of the tax gene, which encodes a viral regulatory protein known to influence host gene expression, can induce within the bone environment marked changes in bone cell activity, resulting in profound skeletal alterations. PMID- 8212555 TI - Regulation of Epstein-Barr virus BamHI-H divergent promoter by DNA methylation. AB - The regulatory mechanisms which control latency and reactivation of the Epstein Barr virus (EBV) are not fully understood. To determine whether DNA methylation is involved, we examined the BamHI-H divergent promoter, which also encompasses the origin for lytic replication (oriLyt) of EBV. The divergent promoter was highly methylated in the stringently latent HH514cl16 cell line and largely unmethylated in the semipermissive FF41-1 cell line. Expression vectors in which the divergent promoter directed transcription of the chloramphenicol acetyltransferase gene were made. Using in vitro methylation and transient transfections, we found an inverse correlation between the number of sites methylated and level of gene expression. Similar patterns of inhibition were observed when the methylated promoter was activated by BZLF1 or BRLF1 and in lymphoid or epithelial cells. The role of two CpG dinucleotides in the BRLF1 binding sites of the divergent promoter was determined by site-directed mutagenesis. The results indicated that site-specific methylation of these CpGs was not solely responsible for inhibition of expression by methylation. DNA methylation also reduced DNA replication mediated by oriLyt. These results suggest that hypermethylation of the divergent promoter and oriLyt may suppress transcription and lytic replication of EBV. PMID- 8212556 TI - Phylogenetic relationships of dengue-2 viruses. AB - RNA oligonucleotide fingerprinting studies on a large number of virus isolates previously demonstrated considerable genetic variation in isolates of dengue (DEN)-2 serotype. We report the entire envelope (E) glycoprotein gene and deduced amino acid sequences of 16 DEN-2 viruses and the phylogenetic relationships of these, plus 17 additional published DEN E gene sequences. Comparison of DEN-2 E glycoprotein gene sequences revealed base substitutions scattered throughout the entire gene with as much as 22% sequence divergence. Aligned E glycoprotein amino acid sequences revealed the viruses differed by as much as 10%. There appeared to be constraints on the overall structure of the E protein to maintain biological function. Clusters of amino acid substitutions were present in the hydrophobic membrane anchor region at the carboxyl terminal end of the protein. Maximum parsimony analysis of the E gene sequences allowed construction of a phylogram indicating evolutionary relationships of the virus isolates within the DEN-2 serotype. Five genetic subtypes were identified. Phylogenetic relationships of the DEN-2 serotype and other flaviviruses based on E protein sequences reflected traditional antigenic and serologic classifications. PMID- 8212557 TI - Analysis of hepatitis C virus capsid, E1, and E2/NS1 proteins expressed in insect cells. AB - The baculovirus/insect cell expression system was used to express the capsid protein and glycoproteins (e1 and e2/NS1) of the hepatitis C virus (HCV). Each polypeptide domain was expressed individually using two different constructs varying at their carboxy termini in order to retain or delete hydrophobic domains that may be involved in membrane association. The capsid proteins were transported to the nucleus where they formed a single large crystal-like inclusion. The capsid proteins were phosphorylated in insect cells. The e1 and e2 polypeptides were present in both the soluble and insoluble cellular fractions. Deletion of a hydrophobic domain in the carboxy terminus of e2 resulted in the polypeptide becoming soluble but not secreted. Deletion of the carboxy terminus of e1 had no effect on solubility. Both e1 and e2 were glycosylated, with variable glycosylation of e1 giving rise to a series of polypeptides varying in apparent molecular weight. Co-infection of insect cells with viruses expressing e1 and e2 resulted in a complex that permitted the coimmunoprecipitation of e1 with antibodies to e2 and vice versa. Immunofluorescence staining of insect cells expressing e1 and e2 indicated that reactivity to e2 was more prevalent in anti HCV positive human sera. PMID- 8212558 TI - Resolution of genotypic and phenotypic properties of herpes simplex virus type 1 temperature-sensitive mutant (KOS) tsZ47: evidence for allelic complementation in the UL28 gene. AB - Herpes simplex virus type 1 (HSV-1) mutant tsZ47 was reported to be temperature sensitive for virus growth and transport of viral glycoproteins to the cell surface and to contain two different mutations (B. A. Pancake, D. P. Aschman, and P. A. Schaffer, (1983) J. Virol. 47,568-585). However, we found that similar amounts of glycoproteins B, C and H were expressed at the cell surface at the permissive and non-permissive temperatures and in addition, tsZ47 virus contained only a single mutation. UL28-null virus, gC delta 7B, failed to complement tsZ47 in mixed infections and tsZ47 replicated in UL28 but not gB transformed cell lines. A ts lesion of tsZ47 was mapped within a 1333 bp region of the UL28 gene by marker-rescue using overlapping DNA fragments. DNA sequencing identified a C to T transversion resulting in an R to W amino acid change at UL28 amino acid position 531. Southern Blot analysis and transmission electron microscopy demonstrated that tsZ47, is defective in cleavage and encapsidation of viral DNA. Mutant virus ts1203 (C. Addison, F.J. Rixon, and V.G. Preston, (1990) J. Gen. Virol. 71, 2377-2384) that contains a mutation in the 5' end of UL28, complemented tsZ47 in mixed infections. This suggests that allelic complementation may be occurring and UL28 may encode a protein with independently functioning domains, or that it participates in a multimer. PMID- 8212559 TI - The visna transcriptional activator Tat: effects on the viral LTR and on cellular genes. AB - U937 promonocytic cells, either treated or untreated with phorbol-esters, were used for transient expression assays. We analyzed a series of visna LTR plasmids containing either the AP-1 or the AP-4 or both target responsive sequences for visna Tat transactivation. A 5' deletion mutant of the LTR containing a truncated AP-4 target sequence lost the Tat-mediated transactivation, while phorbol ester mediated transactivation was not affected. Furthermore, the absence of this AP-4 sequence dramatically decreased the additive effect observed when U937 cells were both treated by phorbol ester and expressed the tat gene product, suggesting a high interdependence of the AP-1 and AP-4 sequences for the regulation of the transcription driven by the visna LTR. The c-Jun/AP-1 factor was a prerequisite for the modulation of the activity of the LTR since no Tat-mediated transactivation was found when transfection experiments were carried out in F9 teratocarcinoma cells which are deficient for AP-1 activity. Because the Tat product enhanced the transcription of the visna LTR via the AP-1 site, we asked whether this viral factor could regulate the expression of cellular factors involved in one of the cellular activation pathways. Northern analysis of U937 cells clearly indicated that visna Tat promoted the c-jun mRNA expression, in contrast to the c-fos mRNA expression. Next, we examined nuclear extracts prepared at various times after infection of permissive ovine cells with visna virus, and showed an increased level in the c-Jun DNA binding activity. These data indicated that viral infection can induce a cellular activation pathway in permissive cells. PMID- 8212560 TI - Penetration of Autographa californica nuclear polyhedrosis virus nucleocapsids into IPLB Sf 21 cells induces actin cable formation. AB - The budded form of Autographa californica nuclear polyhedrosis virus functionally enters cells by adsorptive endocytosis. During the period of virus uptake into Spodoptera frugiperda IPLB Sf21 cells (1 to 4 hr postinfection), filamentous F actin cables, visualized by fluorescence microscopy, were formed within the cytoplasm of infected cells. Cable formation appeared to be a direct effect of viral inoculum in that the numbers of observed cables increased with an increase in multiplicity of infection, and cable formation was not dependent on protein synthesis. Cable induction was first apparent around 30 min postinfection, although uptake of virus into endocytic vesicles began much earlier. Chloroquine, a chemical that prevents release of nucleocapsids from endosomes, inhibited cable formation. Similarly, when virus adsorbed to the exterior of cells was exposed to neutralizing antibody, release of nucleocapsids from endosomes and subsequent cable induction were prevented. Careful observation of co-labeled F-actin cables and nucleocapsids revealed a single nucleocapsid at an end of most cables. These results suggested that nucleocapsids or nucleocapsid-associated proteins of budded virus induced the polymerization or bundling of actin following their penetration into the cytoplasm from endocytic vesicles. PMID- 8212561 TI - Cell fusion activity of the simian immunodeficiency virus envelope protein is modulated by the intracytoplasmic domain. AB - The processing and biological activity of envelope glycoproteins of pathogenic and nonpathogenic simian immunodeficiency viruses (SIVs) was compared using recombinant vaccinia viruses (rVVs). The env glycoprotein of the nonpathogenic SIVmac1A11 virus caused much larger and more numerous syncytia than the glycoprotein of the pathogenic SIVmac239 virus in several CD4+ human cell lines. The env gene of SIVmac239 codes for a full-length transmembrane (TM) protein, while the SIVmac1A11 virus has a TM protein with a markedly truncated cytoplasmic domain. To determine if TM protein truncation alone might affect the biological properties of viral glycoproteins, we constructed a rVV which expresses a SIVmac239 env with a site-specific mutation yielding a truncated TM protein. This truncated env protein induced extensive fusion of rVV-infected HeLa T4 cell monolayers, whereas no fusion was observed for the parental SIVmac239 env recombinant. The truncated glycoprotein also caused larger and more numerous syncytia than the wild-type SIVmac239 glycoprotein in the human cell lines HUT 78 and CEM x 174. The mutation altered env glycoprotein transport, but did not significantly affect cell surface expression levels or the amount of secreted soluble SU protein. In coinfection assays, the full-length SIVmac239 env protein was found to interfere with fusion induced by the truncated envelope protein. The results thus demonstrate that changes in the cytoplasmic domain of the SIVmac envelope protein can markedly affect the ability to induce cell fusion, an activity of the external domains of the TM-SU glycoprotein complex. PMID- 8212562 TI - The NS 3 nonstructural protein of flaviviruses contains an RNA triphosphatase activity. AB - The genome of flaviviruses consists of an infectious single-stranded RNA molecule which contains a type 1 cap structure at the 5'-terminus. The cap is synthesized by RNA triphosphatase, guanylyltransferase and methyltransferase. Since flaviviruses replicate in the cytoplasm, it can be assumed that these functions are performed by virus-coded proteins. We previously showed that subtilisin treatment of membranes isolated from cells infected with the West Nile flavivirus results in release of a 50 kDa molecular weight fragment of the viral nonstructural protein NS 3. This so-called p50-S protein contains the residue gly (168) of NS 3 at the amino-terminus and represents an RNA-stimulated NTPase. In the present report we present experimental evidence which indicates that the p50 S protein also contains the active site of an RNA triphosphatase. The activity specifically cleaves the beta,gamma-triphosphate bond at the 5'-terminus of RNA. The localization of NS 3 protein sequence elements with known functions indicates that this multifunctional protein contains a protease in the amino-terminal part, a helicase in the central region and the RNA triphosphatase in the carboxy terminal domain. An amino acid sequence element which may be involved in recognition of the 5'-terminal RNA triphosphate is tentatively identified. A homologous element may be present in the vaccinia virus-coded RNA triphosphatase. PMID- 8212563 TI - Mutational analysis of the nucleic acid-binding 17 kDa phosphoprotein of potato leafroll luteovirus identifies an amphipathic alpha-helix as the domain for protein/protein interactions. AB - The 17 kDa protein (pr17) of potato leafroll luteovirus is translated from a subgenomic PLRV RNA by internal translation initiation and binds to single stranded nucleic acids (E. Tacke, D. Prufer, J. Schmitz, and E. Rohde, 1991, J. Gen. Virol. 72, 2035-2038). Chemical crosslinking of in vitro expressed pr17 provided evidence for the preferential formation of pr17 homodimers which were also detected in PLRV-infected potato plants and isolated from potato lines expressing the PLRV pr17 transgene. Mutation analysis identified an amphipathic alpha-helix within the acidic amino-terminus of pr17 which acts as the domain for protein/protein interactions. Pr17 was predominantly associated with subcellular fractions enriched for nuclei, chloroplasts, mitochondria, and membranous structures. In addition it was shown that pr17 was phosphorylated in planta and that this modification did not inhibit binding of the protein to nucleic acids. PMID- 8212564 TI - Paracrystalline structure of cauliflower mosaic virus aphid transmission factor produced both in plants and in a heterologous system and relationship with a solubilized active form. AB - Cauliflower mosaic virus (CaMV) aphid transmission factor (ATF), produced in a baculovirus expression system, forms paracrystalline structures, as demonstrated by electron microscopic observations. Similar paracrystals were also found in CaMV-infected plants, using immunogold techniques, thus providing the first evidence of such a structure for the CaMV ATF (P18). We demonstrated that the paracrystals can be solubilized to provide an active form of the CaMV ATF which can also be reverted into the paracrystalline aggregated form. This suggests that the paracrystalline structures might act as a source of active CaMV ATF or be the form in which it is stored within the infected cells. A point mutation within the CaMV gene II (which encodes the ATF) leads to the loss of both the paracrystalline structures and the ATF activity. Hence, the paracrystalline structure seems to be a feature of the native (unmodified ) CaMV ATF. PMID- 8212565 TI - A feature of the coat protein of potato virus X affects both induced virus resistance in potato and viral fitness. AB - The coat protein of PVX determines whether isolates of PVX are affected by Rx mediated resistance in potato. Isolates with the coat protein of PVXHB are not affected by the resistance; those with the coat protein of PVXUK3 elicit an extreme resistance in the Rx potato that prevents virus accumulation, even on the inoculated leaf. In this paper we describe the analysis of a series of hybrid and mutant isolates of PVXHB and PVXCP4 which were inoculated to plants and protoplasts of Rx and rx cultivars of potato. From the virulence phenotypes of these isolates we conclude that elicitation of the resistance is affected by amino acids 121 and 127 of the viral coat protein, with codon 121 being the major determinant. PVXHB and hybrid or mutant isolates with lysine and arginine at positions 121 and 127 were able to overcome the resistance of Rx, whereas those with threonine and arginine were resistance sensitive both on plants and in protoplasts. The viral isolates with single mutations at either codon 121 or 127 were less infectious than the wild-type or double mutant isolates although, in protoplasts of the susceptible cultivar of potato, they accumulated as well as the wild-type virus. Taken together these data suggest that amino acids 121 and 127 affect a feature of the viral coat protein which may interact with cellular components involved in the spread of PVX and with the product of the Rx resistance gene. PMID- 8212566 TI - Interferons inhibit onset of murine cytomegalovirus immediate-early gene transcription. AB - Treatment of NIH 3T3 fibroblasts with interferon-alpha or interferon-gamma (IFN alpha or IFN-gamma) significantly reduced murine cytomegalovirus (MCMV) replication. Determination of viral DNA in the nuclei of the infected cells before onset of DNA replication demonstrated that virus uptake, transport to the nucleus, and DNA stability were not decreased. Analysis of the virus specified mRNAs soon after infection revealed that in the cells exposed to IFNs expression of the immediate early (IE) genes was strongly reduced. Nuclear run-off transcription analysis showed that this inhibition is due to significant reduction of IE gene transcription rates following IFN treatment. Since transcription of the MCMV IE region is regulated by a strong enhancer element, a construct containing the chloramphenicol acetyltransferase (CAT) reporter gene, driven by an 1.2 kb segment spanning the enhancer and IE1/3 promoter region of the IE transcription unit, was transfected into NIH 3T3 cells. Treatment with IFN alpha or IFN-gamma after transfection strongly reduced CAT activity compared to untreated controls. In an attempt to define a negative IFN-responsive element in the IE enhancer, a series of deletion mutants driving the CAT reporter gene were transfected into NIH 3T3 cells that were then treated with IFN-alpha. With the sole exception of the construct containing the minimal MCMV IE1/3 promoter (-102 to the cap site), all other deletion mutants were strongly down-regulated by IFN alpha-treatment. Taken as a whole, these results suggest that IFNs inhibit MCMV replication by impairing the transcription of the IE transcription units, and that this negative regulation is carried out by sequences scattered throughout the IE enhancer region. PMID- 8212567 TI - Characterization of the foot-and-mouth disease virus 3C protease expressed in Escherichia coli. AB - We have constructed a clone encoding the foot-and-mouth disease virus (FMDV) 3C protease gene (p3C) using the polymerase chain reaction. The construct was engineered to contain initiation and termination codons and cloned into a plasmid under the control of the bacteriophage T7 promoter. The p3C gene was expressed both in an in vitro transcription-translation system and in vivo in an Escherichia coli system containing an inducible T7 RNA polymerase gene. In both systems the expressed products were of the appropriate molecular weight and immunologically reactive with bovine convalescent serum. E. coli-expressed 3C protein was mainly found in the insoluble fraction of cell lysates. The E. coli expressed protease was assayed in an in vitro system with radiolabeled P1 capsid precursor protein and P2 precursor protein as substrates. E. coli-expressed 3C completely processed the P1 and P2 precursors into mature capsid and nonstructural proteins, respectively. The kinetics of processing of P1 by E. coli expressed 3C revealed the following order of cleavage: VP3-VP1, VP0-VP3, VP1-2A. PMID- 8212568 TI - The effects of serpin gene mutations on the distinctive pathobiology of cowpox and rabbitpox virus following intranasal inoculation of Balb/c mice. AB - Intranasal infection of Balb/c mice with 106 plaque forming units (PFU) of wild type cowpox virus (CPV) and rabbitpox virus (RPV) induced strikingly different pulmonary pathology despite nearly identical clinical signs of illness and LD50. Intranasal infection with CPV induced severe peribronchial, peribronchiolar, and perivascular hemorrhage with a mixed inflammatory cell infiltrate, bronchial and bronchiolar epithelial cell hyperplasia with intracytoplasmic acidophilic inclusion bodies, and alveolar hemorrhage and edema. In contrast, infection with RPV induced a mixed peribronchial and peribronchiolar inflammatory cell infiltrate, multifocal areas of bronchiolar epithelial cell coagulation necrosis, alveolar edema, and a conspicuous absence of pulmonary hemorrhage. Viremia was not detected following CPV infection and only 1 of 11 mice had brain-associated virus at death. Mice infected with RPV exhibited a viremia 2-3 days after infection and all mice had virus associated with the brain at death. Mice infected with viruses containing certain serine protease inhibitor (SPI) gene mutations (CPV delta SPI-1, CPV delta SPI-3, and RPV SPI-1-) exhibited no difference in clinical disease manifestation when compared with those infected with wild-type viruses. However, inactivation of the SPI-2 genes in either CPV or RPV resulted in disease attenuation and alteration of pulmonary pathology. Mice infected with the CPV delta SPI-2 mutant showed decreased pulmonary hemorrhage, reduced inflammation, and an absence of alveolar edema, while mice infected with the RPV delta SPI-2 mutant had a marked increase in intrapulmonary inflammatory cells and only a transient viremia. PMID- 8212569 TI - Characterization of productive and non-productive AcMNPV infection in selected insect cell lines. AB - We have investigated the process of productive and non-productive AcMNPV infection in a variety of cultured insect cells including lines derived from Spodoptera frugiperda (IPLB-SF21), Mamestra brassicae (SES-MaBr-3), Choristoneura fumiferana (IPRL-CF-1), Bombyx mori (BmN-4), Lymantria dispar (IPLB-Ld652Y), Helicoverpa zea (Hz1b3), and Drosophila melanogaster (Dm). In each cell line, we have examined viral utilization of an early, a late, and a very late promoter, the replication of viral DNA and the production of budded virus (BV) and polyhedral inclusion bodies (PIBs). Analysis of promoter use on the single cell level was performed using fluorescence-activated cell sorting (FACS) technology. Cell cultures were infected with recombinant viruses containing CAT reporter genes under the transcriptional control of viral early, late or very late promoters. Cells were immunostained to detect the CAT gene product and the relative CAT content of infected cells on a per cell basis was determined by FACS analysis. Productive infection of IPLB-SF21 cells involved essentially 100% of the cells while analysis of less productive lines (IPRL-CF-1 and SES-MaBr-3) suggests that the virus initiates and completes the replication process only in a subpopulation of cells. Analysis of non-productive infections (in BmN-4, IPLB Ld652Y, Hz1b3, Drosophila Schneider) revealed different patterns of viral DNA replication and promoter use in each cell line suggesting a variety of obstacles to productive infection. PMID- 8212570 TI - Promoter, spliced leader, and coding sequence for BICP4, the largest of the immediate-early proteins of bovine herpesvirus 1. AB - We report the complete nucleotide sequence of the bovine herpesvirus 1 (BHV-1) immediate-early gene encoding BICP4, the homolog of the ICP4 protein of herpes simplex virus. Combined with previous mapping studies, the sequence analysis revealed that the transcript for BICP4 consisted of a noncoding leader RNA (exon 1; 0.35 kb) separated by an intron (0.46 kb) from the main body (exon 2; 4.1 kb). The open reading frame for BICP4 (1343 amino acid residues) started 27 nt after the splice site and extended across exon 2 for most of its length, BICP4 contained two domains of high homology (regions 2 and 4), which had been recognized earlier to be most conserved in the ICP4 homologs of alpha herpesviruses and to be functionally important. These domains were flanked by three regions of lower but still discernible homology. Unique features of BICP4 were two large clusters of glutamic acid residues near the end of region 3, and the displacement of a polyserine tract to region 5, which in all other ICP4 homologs residues near the end of region 1. Transient expression assays showed that BICP4 repressed its own promoter and activated other herpes-virus genes. The 8.1-kb sequence summarized here completes analysis of the inverted repeats of the BHV-1 genome; it includes a segment (2.5 kb) upstream of the BICP4 gene apparently devoid of coding sequences but containing numerous scattered transcription signals. PMID- 8212571 TI - The CAEV tat gene trans-activates the viral LTR and is necessary for efficient viral replication. AB - Caprine arthritis-encephalitis virus (CAEV) is a lentivirus which is closely related by nucleotide sequence and biological properties to visna virus. Sequence analysis of the CAEV genome revealed the presence of a small open reading frame (ORF) which shares amino acid identity with the visna virus tat gene. Using an infectious molecular clone of CAEV the role of the tat ORF in viral replication was examined. Mutations were made in the tat ORF that introduced two in frame stop codons six amino acids downstream of the tat AUG; in addition, a deletion mutant was made that removed most of the tat ORF. Both of these mutants had greatly reduced virus titers (> 1000-fold less than the wild type infectious clone). Co-transfection of a tat expressing plasmid with these viruses containing the tat ORF mutations resulted in higher levels of virus production demonstrating that the effects of both mutants are tat specific. These mutants provide data that the CAEV tat gene is necessary for efficient virus replication. Analysis of the RNA in these transfected cells showed that complementation of the tat gene was in trans and not the result of recombination. Analysis of the gag and rev proteins in the transfected cells demonstrated that these proteins were not detectable in cells transfected with the tat mutants but could be readily detected when the mutations were complemented in trans with a tat expression vector. To test for tat mediated trans-activation a plasmid expressing the CAEV tat ORF was co-transfected with plasmids containing either the CAEV or visna virus LTR driving transcription of the bacterial chloramphenicol acetyltransferase gene (CAT). These experiments indicate that one function of the CAEV tat protein is to trans-activate gene expression from the viral promoter. RNase protection analysis of CAT mRNA from co-transfected cells demonstrated that CAEV Tat trans-activates gene expression by increasing steady-state levels of mRNA. PMID- 8212572 TI - Expression of the Epstein-Barr virus immediate early gene, BZLF1, in nasopharyngeal carcinoma tumor cells. AB - The Epstein-Barr virus has been shown to be associated with nasopharyngeal carcinoma (NPC). We have shown that anti-ZEBRA transactivator antibodies were present in sera of most NPC patients. We investigated the expression of the BZLF1 gene in fresh NPC tumor biopsies. RNA transcripts of this gene could be detected by in situ hybridization. This expression is restricted to tumor cells and is not present in infiltrating lymphocytes. ZEBRA protein could also be visualized in a fraction of these cells. A cDNA library made from polyadenylated mRNA of an NPC tumor biopsy was constructed and analyzed by PCR. Transcripts of the BZLF1 gene were unspliced, incompletely spliced, or fully processed. A transcript lacking the middle exon was also observed. Fully processed BZLF1 mRNA was also detected in six more NPC tumor biopsies. PMID- 8212573 TI - The tryptophan bridge is a critical feature of the papillomavirus E2 DNA binding domain. AB - The papillomavirus E2 protein is a DNA binding protein that regulates viral transcription and replication. E2 binds DNA as a dimer. Recent crystallographic data for E2 complexed to DNA revealed that novel peptide structures in E2 mediated dimerization and DNA binding. To identify important features of these motifs we have used limited proteolysis and urea denaturation as biochemical probes for structure, applying these techniques to E2 alone, E2 bound to DNA, cross-linked products, and mutants that were targeted at Trp360, a contact point along the dimer interface. DNA binding stabilized E2 structure, shifting the point at which it denatures from 5 to 7.6 M urea. In contrast, Trp360 mutant proteins, while dimeric, were more sensitive to denaturation by urea when bound to DNA. The most striking results came from uv cross-linking studies in which Trp360 was targeted as the site of cross-linking. Ultraviolet cross-linking dramatically increased the resistance of E2 to proteolysis regardless of the protease tested and with no deleterious effect on the affinity of E2 for DNA. Cross-linking through Cys356 with bismaleimidohexane did not promote stabilization. The ability to stabilize or destabilize E2 by Trp360-targeted modifications demonstrates the importance of the Trp360-Trp360 interaction, which may represent a general feature of the beta-barrel motif. PMID- 8212574 TI - Evidence that the epidermal growth factor receptor on host cells confers reovirus infection efficiency. AB - Reovirus binds to multiple sialoglycoproteins on the host cell surface. In an attempt to probe additional specific determinants that dictate host cell susceptibility to reovirus infection, we found that two mouse cell lines (NR6 and B82) previously shown to express no endogenous epidermal growth factor (EGF) receptors were relatively resistant to reovirus infection, whereas the same cell lines transfected with the gene encoding the EGF receptor manifested significantly higher susceptibility as determined by induction of cytopathic effects, viral protein synthesis, and plaque titration. This enhancement of infection efficiency requires a functional EGF receptor since it was not observed in cells expressing a mutated (kinase-inactive) EGF receptor. The observed difference in infection efficiency is not due to differences in virus binding or internalization. These studies suggest that the reovirus infection process is closely coupled to the EGF receptor-mediated cell signal transduction pathway. PMID- 8212575 TI - Recognition of the epidermal growth factor receptor by reovirus. AB - The demonstration that alpha-sialic acid is the minimal determinant recognized by human reovirus is compatible with the finding that this virus binds to multiple sialoglycoproteins on the host cell surface. However, the identities of these proteins have remained unknown. By applying detergent-solubilized plasma membranes from the human epidermoid carcinoma A431 cell line to immobilized reovirions, we have identified the 150- to 170-kDa epidermal growth factor (EGF) receptor as one of the cell surface proteins recognized by reovirus. Direct interaction between the N-terminal extracellular domain of the EGF receptor and reovirus was confirmed by the demonstration that of a number of proteins secreted by A431 cells, the 105-kDa N-terminal cell surface domain of the EGF receptor was the major protein recognized by the virus. However, as expected, reovirus and EGF did not compete for the same binding site on the EGF receptor of intact A431 cells. PMID- 8212576 TI - Synergistic inhibition of HIV-1 by CD4 binding domain reagents and V3-directed monoclonal antibodies. AB - Human immunodeficiency virus (HIV) binds to the surface of CD4 positive lymphocytes and monocyte/macrophages via a high affinity interaction between CD4 and the HIV envelope glycoprotein gp120 and is internalized by fusion of the virus and the cell membrane. The third variable (V3) domain of gp120 also plays a central role in the fusion and viral entry process. Reagents that neutralize HIV by binding to the CD4 binding domain or V3 domain of gp120 have been proposed as therapeutics in the post-HIV exposure and perinatal setting. However, the neutralization potency of these proposed reagents, sCD4, V3 directed and CD4 binding domain directed monoclonal antibodies (MAbs), is intermediate at best and may be of limited use in a clinical setting. We have demonstrated that the combination of reagents to these two primary targets for neutralization resulted in synergy with 10- to 1000-fold increase in virus neutralization. The addition of these combined reagents a second time 3 and 5 days postinfection resulted in an additional 10-fold increase in neutralization suggesting a block in HIV spread from cell to cell. These data suggest that a combination of CD4 binding domain reagents and V3 antibody infused at intervals may significantly reduce the viral load in AIDS patients. PMID- 8212577 TI - Myristoylation-enhanced binding of the HIV-1 Nef protein to T cell skeletal matrix. AB - The negative factor, Nef, of HIV-1 was found to associate to an extent of 16-42% with the detergent insoluble cytoskeletal fraction of T lymphocytes. Furthermore, Escherichia coli expressed Nef protein was found to bind during in vitro reactions with the cytoskeletal matrix to an extent of 30-50%. Cytoskeletal association of Nef was significantly enhanced by myristoylation. The specificity of the myristoylation-enhanced binding was demonstrated by the lack of an effect of myristoylation on binding of the HIV-1 Gag protein to the cytoskeleton. Cytoskeletal binding was saturable, and inhibited by high concentrations of sodium chloride, or with SDS or urea. Binding of Nef to the cytoskeletal matrix may be important in mediating its effects on HIV-1 replication. PMID- 8212578 TI - Identification of a new subgroup of SIVagm in tantalus monkeys. AB - Simian immunodeficiency viruses from African green monkeys (SIVagm) can be classified into three subgroups based upon the species from which they were isolated. The most extensively studied subgroup are composed of SIVagm isolated from vervet monkeys (Cercopithicus pygerythrus). Fewer isolates have been characterized from either grivets (Cercopithicus aethiops) or green monkeys (Cercopithicus sabeus). An additional distinct species of African green monkeys, tantalus monkeys (Cercopithicus tantalus), has not been characterized in terms of SIV infection. A high seroprevalence of SIV-specific antibodies was identified in sera collected from Ugandan tantalus monkeys. SIV was isolated from PBMC (SIVagm/tan), the gag region amplified by polymerase chain reaction, cloned, and sequenced. Based upon gag, SIVagm/tan isolates cluster genetically with other previously recognized SIVagm strains. However, SIVagm from tantalus monkeys forms a distinct genetic subgroup. These data confirm earlier observations of species specific subtypes of SIVagm viruses and support the hypothesis that these viruses may have coevolved with their host during geographic dispersion throughout Africa. PMID- 8212579 TI - Spontaneous and inducible epidermal hyperplasia in transgenic mice expressing HIV 1 Nef. AB - The pathophysiological consequence of HIV-1 nef gene expression was investigated in transgenic mice carrying a cDNA for Nef linked to either the HIV-1 LTR or the MMTV LTR. In HIV/Nef transgenic mouse lines, nef expression was detected exclusively in the skin and a significant fraction of HIV/Nef transgenic animals (30-75%, depending on the line) spontaneously developed discrete proliferative skin lesions resembling papillomas that were often accompanied by a progressive ulceration of the epidermal cell layer. Nef protein was detected in the basal cell layer of the epidermis and was elevated in the proliferating epidermis. Epidermal cell proliferation could be induced by UV-C irradiation of HIV/Nef transgenic animals but not control mice. An increase in nef expression in the skin accompanied this proliferation. MMTV/Nef mouse lines expressed Nef RNA and protein in organs typically permissive for MMTV LTR-directed transcription but with no obvious pathological consequence. PMID- 8212580 TI - Fowlpox virus host range restriction: gene expression, DNA replication, and morphogenesis in nonpermissive mammalian cells. AB - Fowlpox virus (FPV), type species of the Avipoxvirus genus, causes a slow spreading pox disease of chickens. Following infection of mammalian cells there is no evidence of productive replication of FPV although cytopathic effects are induced and FPV recombinants have been shown to express foreign genes from vaccinia virus early/late promoters. Here we report results of a study to investigate the expression of FPV genes, the replication of FPV genomic DNA, and any ultrastructural changes in mammalian cells infected by wild-type virus, undertaken as a first step in elucidating the nature of the block (or blocks) to productive replication of FPV in mammalian cells. Early and late gene expression as well as genomic DNA replication was observed in fibroblast-like cell lines of monkey and human origin. Furthermore, viral morphogenesis was observed in monkey cells, with the production mainly of immature particles though smaller numbers of apparently mature virus particles were observed. PMID- 8212581 TI - Mapping the 5'-terminus of rice tungro bacilliform viral genomic RNA. AB - The initiation site of the major transcript of rice tungro bacilliform virus (RTBV) has been located by mapping the 5' end of the RNA to nucleotides 7404 and 7405 of the RTBV genome using an RNase protection method. This was confirmed by the 5' RACE PCR procedure which mapped the 5' end of the RNA to nucleotide 7405. These results are consistent with data from our analysis of the strong-stop DNA of RTBV. A eukaryotic RNA polymerase II promoter sequence (TATATAA) was located at nucleotide 7373 of RTBV genome which is 31-32 nucleotides upstream from the proposed initiation site of the RTBV transcript. PMID- 8212582 TI - Identification and analysis of the transport/capsid assembly protein (tp/cap) gene of human herpesvirus-6 (HHV6). AB - The transport/capsid assembly protein (tp/cap) gene of human herpesvirus 6 (HHV6) strain U1102 has been identified and localized on the restriction enzyme map of the viral genome, to the EcoRI-Q fragment. The complete DNA sequence of the tp/cap gene was determined. The tp/cap gene encodes a protein product of 726 amino acids and has the strongest similarity with the homologous gene (HCMV UL56) from HCMV. Upstream of the tp/cap open reading frame is the gene for the major DNA binding protein (mdbp) and downstream is the glycoprotein B (gB) gene. This gene block arrangement is common to all herpesviruses. PMID- 8212583 TI - DNA sequence of a simian varicella virus gene that encodes a homologue of varicella zoster virus IE62 and herpes simplex virus ICP4. AB - Clinical and biological studies indicate that simian varicella virus (SVV) infection of primates is the counterpart of human varicella zoster virus (VZV) infection. We have identified an SVV open reading frame (ORF) that is homologous to the VZV protein IE62 and herpes simplex virus (HSV) ICP4. Like the genes encoding the VZV and HSV proteins, the SVV gene is located in the repeat region of the virus genome. Its expression in SVV-infected cells yields a 4.2-kb transcript. DNA sequencing of the SVV gene reveals a coding region 3834 nucleotides in length and a G+C content of 60.3%. Like ICP4 homologues in other herpesviruses, the SVV protein has five regions, two of which (regions 2 and 4) are highly conserved. The SVV protein also contains a run of serine residues in its amino terminus that is characteristic of herpesvirus ICP4 homologues. The SVV protein shows an overall homology of 24% to HSV ICP4 and 53% to VZV IE62. PMID- 8212584 TI - Propagation of human papillomavirus type 11 in human xenografts using the severe combined immunodeficiency (SCID) mouse and comparison to the nude mouse model. AB - We report propagation of human papillomavirus (HPV) type 11 in human xenografts in the severe combined immunodeficiency (SCID) mouse and compare this new animal model for HPV infection to the previously established athymic nude mouse model. HPV-11-infected foreskin fragments grafted under the renal capsule of SCID mice formed large epithelial cysts that had the histologic and immunocytochemical features of HPV infection. This infection was successfully passaged to nude mice. Viral particles that reacted to an antibody directed to HPV-11 virions were identified from samples recovered from the SCID and nude mice. Viral DNA sequence analysis confirmed that the passaged virus was HPV-11. In a comparative experiment of the nude mouse and SCID mouse models, the latter produced HPV-11 infected xenografts that were larger and more often positive for HPV by immunocytochemistry and presence of viral mRNA than those propagated in the former model. Finally, we observed that growth of HPV-11-infected foreskin fragments in the SCID mouse model is not restricted to the kidney as in the nude mouse, but also can occur in the subcutis and the peritoneum. PMID- 8212585 TI - Demonstration of circularization of herpes simplex virus DNA following infection using pulsed field gel electrophoresis. AB - Studies of the configuration of intracellular herpes simplex virus DNA have been limited by the inability of restriction enzyme analyses to distinguish circular DNA from other configurations. To address this issue, we used pulsed-field gel electrophoresis of virus-infected, cycloheximide-treated cells and detected accumulation of viral DNA that failed to migrate out of the sample wells of the gels. This DNA lacked terminal restriction fragments and could be converted to unit-length linear species by gamma-irradiation, demonstrating the circularization of viral DNA following infection. PMID- 8212586 TI - Cytotoxic T lymphocytes cleanse viral gene products from individually infected neurons and lymphocytes in mice persistently infected with lymphocytic choriomeningitis virus. AB - Lymphocytes and/or monocytes/macrophages carry viral genetic information in most, if not all, persistent and latent viral infections, and serve as potential reservoirs for maintaining or reintroducing the infection. Similarly, neurons can be persistently infected by several DNA and RNA viruses whose continued presence can alter the physiologic function of these cells, leading to disorders in neurotransmitters and disease. Here, we document that adoptive transfer of virus specific cytotoxic T lymphocytes clears virus and viral nucleic acid sequences, in vivo, from individually infected lymphocytes, macrophages, and neurons. By plaquing, infectious center, Northern blot, and in situ hybridization at the single cell level, virus was efficiently removed from these cells. PMID- 8212587 TI - Detection of the L protein of tomato spotted wilt virus. AB - The 5'-terminal and 3'-terminal parts of the single open reading frame (ORF) in the L RNA of tomato spotted wilt virus (TSWV) were expressed using a prokaryotic expression system. Using antibodies raised against the translational products obtained a 330-kDa protein could be specifically detected in preparations of purified virions and in nucleocapsid preparations from TSWV-infected leaf tissue. The results obtained indicate that the L protein of TSWV, though much larger than that of the animal-infecting bunyaviruses, is present in virus particles in an unprocessed, intact form. PMID- 8212588 TI - Phosphorylation of the Sendai virus C proteins. AB - We show that the Sendai virus C' and C proteins exist as both phosphorylated and nonphosphorylated forms, while the Y1 and Y2 proteins are not phosphorylated in virus-infected cells. Phosphorylation occurs primarily on serine residues, most likely at the N-terminus of the C' and C proteins. Phosphatases PP1 and PP2A significantly modulate the phosphorylation status of the C proteins as evidenced by okadaic acid inhibition of these phosphatases. The other Sendai virus proteins including the cotranslationally expressed P protein are not necessary for the appropriate phosphorylation of the C' and C proteins. Differential phosphorylation and potential for the modulation of phosphorylation suggests regulatory functions for the C proteins. PMID- 8212589 TI - Genetic analysis of aquareoviruses using RNA-RNA blot hybridization. AB - The relative mobility of the 11 dsRNA genomic segments of 19 Aquareovirus isolates from fish and shellfish were compared by polyacrylamide gel electrophoresis. This study revealed distinct variations of electrophoretic profiles (electropherotypes) of many aquareovirus isolates. No correlation was observed between the electropherotype and the species from which the isolates were obtained, but there was correlation with the geographic site of isolation. Using reciprocal RNA-RNA dot blot hybridization under high-, medium-, and low stringency conditions five different genetic groups (genogroups) could be established (designated A through E). RNA-RNA hybridization showed that segment 10, the genome segment that codes for the major outer capsid protein, was the most variable gene. No genetic relationship was observed between these aquareoviruses and rotaviruses in groups A and C. PMID- 8212590 TI - Immune-based resistance to the formation of v-src-induced distal tumors. AB - Although v-src, the oncogene of Rous sarcoma virus, has been shown to be capable of inducing lethal tumors at visceral sites distal to the primary tumor mass, the mechanisms opposing visceral tumor formation remain to be elucidated. In the present study, we show that visceral tumors, many of which represent a metastasis spawned by the primary mass, are found only in hosts exhibiting reduced levels of tumor immunity. We conclude that it is the weakness of the tumor immune response, rather than a lack of expression of tumor antigen on visceral tumor cells, that is a major underpinning of the formation of v-src-induced visceral tumors. PMID- 8212591 TI - A mutation of the nucleoside triphosphate phosphohydrolase I (NPH-I) gene confers sensitivity of vaccinia virus to interferon. AB - The role of vaccinia virus nucleoside triphosphate phosphohydrolase I (NPH-I) in determining the resistance of this virus to alpha-interferon (IFN) was analyzed by using a well-defined temperature-sensitive mutant (ts36) in the NPH-I gene. Detailed analysis of viral proteins and mRNAs produced in cultured cells treated with or without IFN-alpha showed a strong inhibition by IFN of the synthesis of late virus polypeptides at the nonpermissive temperature, e.g., 83.8% inhibition for the luciferase reporter gene, which is associated with a decrease in steady state mRNA levels. Sensitivity of ts36 to IFN was only the consequence of the point mutation in the NPH-1 gene, as shown by characterization of the rescued virus, R36. Our findings demonstrate that functional NPH-1 is required, at least in part, for resistance of vaccinia virus to IFN. PMID- 8212592 TI - Complementation and recombination between mutants of complementary sense genes of DNA A of Abutilon mosaic virus. AB - Mutations have been inserted into the complementary sense ORFs of DNA A of Abutilon mosaic virus (AbMV). Mutation in both ORF AC1 and ORF AC2/3 resulted in clones incapable of infecting Nicotiana benthamiana following agroinoculation. Mutation in ORF AC1 but not in ORF AC2/3 prevented DNA replication in leaf discs. Thus ORF AC1 is essential for AbMV DNA replication whereas ORF AC2/3 is probably involved in some aspect of the spread of the virus through the plant. Coagroinoculation of both mutants and wild-type DNA B resulted in complementation and recombination. Complementation precedes recombination and once recombination is established mutant DNA can no longer be detected. Plants in which complementation alone is occurring are symptomless and contain relatively low amounts of virus double-stranded DNA whereas following recombination a wild-type infection is established. PMID- 8212593 TI - Nucleotide sequences of the VP4 and VP7 genes of a Chinese lamb rotavirus: evidence for a new P type in a G10 type virus. AB - The VP7 and VP4 genes of a group A rotavirus (Lp14) isolated from a lamb with diarrhea in Qinhai province, China, in 1981 were reverse transcribed, amplified by PCR, cloned, and sequenced. The virus was found to possess a VP7 gene, classifying it as a G10 type, and a VP4 gene which showed only limited homology with any other known VP4 gene, suggesting its classification as a new P type and providing further evidence for the vast diversity of group A rotaviruses. PMID- 8212594 TI - Characterization of poliovirus conformational alteration mediated by soluble cell receptors. AB - Soluble extracts of Spodoptera frugiperda cells expressing the poliovirus receptor (PVR) induce the native poliovirus (PV) to "A" particle conformational change (J. Virol. 64, 4697-4702). We describe the variables that regulate this passage and study the suitability of solubilized PVR both for use as an in vitro system to characterize the receptor-mediated conformational alteration and for the production of large amounts of altered virus for structural analysis. PVR seems to function in a stoichiometric fashion and the A particles produced appear as intact, stain excluding, spherical structures by electron microscopy, regardless of the extensive proteolysis of the capsid protein VP1, which takes place during the conversion. The products obtained, time course, and temperature and ionic strength dependence of the alteration of PV by the solubilized PVR are indistinguishable from those of the alteration that leads to productive infection in cultured cells. Therefore, solubilized PVR may provide a convenient in vitro system for further characterization of the cell entry process. PMID- 8212595 TI - Analysis of cis-acting sequences essential for coronavirus defective interfering RNA replication. AB - Mouse hepatitis virus (MHV) defective interfering (DI) RNA was used to determine the cis-acting sequences required for MHV RNA replication. A 2.2-kb-long cDNA clone of the MHV DI RNA DIssE was used to test the effect of deletions throughout the DI RNA on replication in DI RNA-transfected, MHV-infected cells. Data from a series of deletion mutants demonstrated that about 470 nucleotides at the 5' terminus, 460 nucleotides at the 3' terminus, and about 135 nucleotides in an internal position approximately 0.9 kb from the 5' end of DI RNA were necessary for DI RNA replication. These data suggested that cis-acting sequences which were necessary for MHV RNA replication required not only terminal sequences but also an internal sequence present at about 3.2 kb from the 5' end of the genome. PMID- 8212596 TI - Minor envelope proteins of duck hepatitis B virus are initiated at internal pre-S AUG codons but are not essential for infectivity. AB - In infected liver tissue three major and several minor duck hepatitis B virus (DHBV) envelope proteins are detectable by immunoblotting. Translation initiation at the second and the most distal internal ATG codon of the Pre-S/S gene is known to lead to synthesis of two major envelope proteins (P36 and P17) whereas the origin of a further major (P28) and other minor envelope proteins is not clear. Therefore, it was investigated whether translation initiation at pre-S ATGs leads to synthesis of these other envelope proteins and, if yes, whether they are components of viral particles and essential for infectivity. Each of the five ATG codons of the pre-S region of an infectious Chinese DHBV genome (DHBV26) was mutated separated by oligonucleotide-directed mutagenesis (point mutations or deletions) and the function of the corresponding mutant viruses were tested in vitro and in vivo. Immunoblot analysis of liver cell extracts or of extracts from hepatoma cells transfected with the DHBV genomes showed expression of minor pre-S proteins of about 35, 33, and 30 kDa. These proteins were not expressed when ATG codons at nucleotide positions 825, 882, and 957, respectively, were mutated. None of the ATG mutations abolished expression of the major P28 pre-S protein. In cell culture supernatants the minor pre-S proteins P35, P33, and P30 were identified as components of viral particles. With the exception of the DHBV genome containing the mutated ATG codon 801 (translation initiation codon for the major P36 pre-S protein) all forementioned DHBV mutant genomes were infectious. These data demonstrate that minor pre-S proteins are initiated at internal AUGs of the pre-S gene and are components of viral particles but are not essential for infectivity. In contrast to previously published speculations, the results also indicate that the major pre-S protein P28 is not initiated at AUG codon 957 but probably produced by proteolysis from larger pre-S proteins. PMID- 8212597 TI - Processing of poly-ubiquitin in the polyprotein of an RNA virus. AB - The RNA genome of several cytopathogenic (cp) strains of the pestivirus bovine viral diarrhea virus (BVDV) contains ubiquitin coding sequences (ucs). In noncytopathogenic BVDV strains, such insertions are missing. Gene expression of BVDV occurs via synthesis of a polyprotein which is subsequently processed by virus-encoded and cellular proteases. The insertion of ucs in the genomes of cpBVDV strains CP14 and Osloss leads to additional cleavages in the viral polyprotein. The respective processing events are mediated by cellular ubiquitin C-terminal hydrolases (UCHs). Release of monomeric ubiquitin (ubi) from the poly ubi fragment encoded by CP14 is achieved by cleavage at the C-terminus as well as at the N-terminus of a complete ubi monomer. This result extends the current knowledge about poly-ubi processing. Processing of the polyprotein of CP14 and Osloss by UCHs generates an 80-kDa protein (p80), the marker protein of cpBVD viruses. Thus, the cp phenotype of both strains is apparently caused by the uptake of the ucs in the viral genome. Since cpBVDV strains arise in cattle in the course of a fatal disease, a direct linkage exists between the insertion of ucs and a lethal disease. PMID- 8212598 TI - Genomic organization and mapping of transcription and translation products of the NADL-2 strain of porcine parvovirus. AB - The NADL-2 strain of PPV was cloned into pUC19 and independent infectious clones were sequenced. This permitted a correction of published sequences and to predict a cruciform structure as an alternative to the 5'-hairpin of the "-" strand. This 5'-end structural covariance is shared with other parvoviruses of the same group and two alternative sequences ("flip" and "flop") were present in the region of the cruciform. Transcript and translation product mapping allowed the prediction of the location of the different expression signals. The 5'-startpoints of the transcripts were located at nucleotides 225 and 2035, respectively, and the polyadenylation site at nucleotides 4829-4833. This indicated that the TATA boxes at 196-TATA and 2004-AATA and the 4813-AATAAA polyadenylation sequence would be functional. Alternative splicing of capsid gene (VP) transcripts (either 2280 AG/GT or 2313-AG/GT spliced with 2386-AG/GA), to maintain or remove the first AUG (at 2287) in the ORF, yielded two 2.9-kb mRNAs containing a nested set of protein coding sequences (VP-1 and VP-2 with predicted molecular mass 80.9 and 64.3 kDa, respectively). Three nonstructural (NS) protein gene transcripts were identified. The 4.7-kb transcript was not spliced in the NS gene and was predicted to code for a 75.5-kDa protein (NS-1; published value of phosphorylated form 84 kDa). The splicing sites of two different 3.3-kb NS transcripts were analyzed. These transcripts were predicted to code for the NS-2 protein (18.1 kDa). Of the two NS 2 transcripts, one had also the VP-intron removed downstream of the NS-2 coding sequences. A 2.9-kb transcript would code for an NS-3 protein (12.4 kDa) although such a protein has not been described before. A flow chart of the information from the viral DNA to the viral proteins is presented and several differences, both for the NS and the VP genes, with closely related parvoviruses are noted. PMID- 8212599 TI - Characterization of the G serotype and genogroup of New Delhi newborn rotavirus strain 116E. AB - We recently reported that the culture-adapted neonatal rotavirus strain 116E represented the first P type 11 human rotavirus, based on the close relationship of its VP4 protein to that of the bovine serotype G10P11 strain B223. In this study, we demonstrated by sequence analysis and cross-neutralization studies that the VP7 protein of 116E is closely related to those of the human serotype G9 strains, F45 and WI61, but distinct from B223 and other rotaviruses. Low-level cross-neutralization was also observed between strains 116E and B223, probably because of the antigenic similarity of their VP4 proteins. We have demonstrated by RNA-RNA hybridization that strain 116E is a reassortant between strains from the Wa and bovine (KK3-like) genogroups, deriving at least seven genes from the former and at least one gene from the latter. Together with the recent identification of serotype G10P11 newborn rotavirus strains in Bangalore, India (M. Das et al., Virology, 194, 374-379, 1993), these results are consistent with the hypothesis that reassortment may be an important mechanism for generation of rotavirus strains of newborns. PMID- 8212600 TI - The National Survey of Family Growth, Cycle IV, evaluation of linked design. AB - Research was undertaken to quantify the effects of costs of alternative methods for selecting sample women for the National Survey of Family Growth (NSFG) from the National Health Interview Survey (NHIS). This report presents estimates of the effects of alternative design options, obtained by statistical modeling techniques, for linking the NSFG with the NHIS; the cost data and the statistical precision of estimates were based on data from the NSFG, Cycle IV. The estimated survey costs and projected response rates for alternative linked design options and for the unlinked design are compared for fixed precision. The findings confirm that substantial gains in the NSFG design efficiency were obtained by linking the NSFG sample design to that of the NHIS. PMID- 8212601 TI - Health conditions among the currently employed. AB - This report presents national estimates of the prevalence and incidence of selected health conditions and their work-related consequences among currently employed persons 18 years of age and over. The major health conditions presented include back pain; hand discomfort; dermatitis; eye, nose, and throat irritation; and work injuries. Also presented are estimates of the distribution of workers on selected physical activities and exposures at work. Data are presented by age, sex, race, ethnicity, education, and broad occupational category. PMID- 8212602 TI - Health characteristics of large metropolitan statistical areas: United States, 1988-89. AB - Annual average estimates of rates or percents of limitation of activity, respondent-assessed health status, restricted-activity days, bed-disability days, work-loss days, school-loss days, physician utilization, hospital utilization, incidence of selected acute conditions, and prevalence of selected chronic conditions are shown by geographic region for all large U.S. metropolitan statistical areas combined and for individual metropolitan statistical areas with populations of at least 1.1 million persons. PMID- 8212603 TI - [A letter from the Czech Internal Medicine Society to all the members of the CIS]. PMID- 8212604 TI - [Response to the article by Fixa, Komarkova, Nozicka: H. pylori in the etiology of ulcer disease and gastritis]. PMID- 8212605 TI - [ACE inhibitors in the treatment of patients after myocardial infarct]. AB - ACE inhibitors are becoming an important part of treatment in patients after acute myocardial infarction if they suffer from asymptomatic dysfunction of the left ventricle (ejection fraction of the left ventricle evaluated by echocardiography or isotope ventriculography 40% or less). It prevents the development of cardiac dilatation, it retards progression of the disease and the development of cardiac failure and reduces the necessity of hospitalization in patients with chronic cardiac failure (stage NYHA II-IV). ACE inhibitors are the drug of choice as they reduce significantly the general mortality of these patients. Treatment should not be initiated in the acute stage but after several days have elapsed after infarction, unless contraindications of treatment are present. Extensive investigations made during the past two years revealed moreover that ACE inhibitors effectively prevent also relapses of myocardial infarction or the development of unstable angina pectoris. Prevention of coronary attacks is most probably due to several effects of ACE inhibitors: a) reduction of blood pressure, b) coronary vasodilatation, c) the antiproliferative action of ACE inhibitors on vascular musculature, d) prevention of progression of atherosclerosis, e) prevention of myocardial hypertrophy, f) the favourable effect on endothelial function. So far we indicate for treatment with ACE inhibitors only patients after acute myocardial infarction with left ventricular dysfunction. Only subsequent research will show whether treatment with ACE inhibitors is of value in patients with preserved left ventricular function. PMID- 8212606 TI - [Atrial-triggered and ventricular-inhibited ventricular VDD pacing with atrial and ventricular single catheter electrodes--the Phymos MPS pacemaker]. AB - Optimal treatment from the haemodynamic aspect in complete atrioventricular block is dual-chamber DDD pacing. It makes possible atrioventricular sequence and adaptability of the frequency of ventricular pacing to the load under the control of the sinoatrial node. DDD pacing calls, however, for an atrial and ventricular electrode on two leads. Italian authors developed in 1984 a pacemaker (PM) PHYMOS (MEDICO ITALIA) which makes possible atrial triggered ventricular VDD pacing by means of a single pass lead with a tripolar electrode. As the first ones in the post-communist countries the authors implanted to six patients a PM PHYMOS MPS. They confirmed that the advantages of the VDD system, as compared with DDD, are the use of a single pass lead. This makes the implantation quicker, simpler and safer and reduces the time of X-ray irradiation and the incidence of electrodes dislocations. Another advantage is the lower incidence of atrial fibrillation and probably also pacemaker mediated tachycardias. The disadvantages of the VDD system are that atrial stimulation is impossible and that the diameter of the single pass lead is somewhat larger. According to data in the literature and the so far small experience of the authors, when the indication is correct- atrioventricular block grade III or II with intact function of the sinoatrial node--the advantages of VDD pacing with a single pass lead, as compared with DDD pacing, predominate over disadvantages. PMID- 8212607 TI - [Atenolol and bisoprolol in the treatment of mild and moderately severe hypertension]. AB - Atenolol and bisoprolol, two beta-1-selective blockers, were compared in patients with mild and medium severe hypertension. Forty patients with a diastolic blood pressure of 95-115 mm Hg were two weeks after discontinuation of treatment divided at random into two groups treated with 50 mg atenolol and 5 mg bisoprolol. If the blood pressure was not affected by this dosage, the dose was raised to 100 mg atenolol and 10 mg bisoprolol. The blood pressure readings, heart rate, side effects of the drugs, laboratory and echocardiographic values were followed up for a period of three months. The authors recorded a marked decline of pressure and heart rate after the first week of therapy, the pressure readings in an upright position did not differ statistically from values in a sitting position, orthostatic hypotension was not recorded. The rate of success of bisoprolol was 85%, of atenolol 75%. During treatment no serious side-effects were observed. The biochemical parameters and echocardiographic values were not altered significantly by treatment. Atenolol and bisoprolol are two effective beta-1-selective blockers with a comparable effect in the treatment of mild and medium severe hypertension. They are useful in monotherapy as well as in combination with other antihypertensive drugs. In hypertension associated with diabetes mellitus, incipient bronchopulmonary disease and pregnancy they are also indicated. They are well tolerated also by elderly patients, an advantage of bisoprolol may be that it has a smaller impact on pressure and heart rate during the night. PMID- 8212608 TI - [Tiracizine in the treatment of ventricular arrhythmia (preliminary study)]. AB - Tiracizine a new antiarrhythmic drug class Ia was tested in a open crossover study in a group of 46 patients with more than 2500 ventricular extrasystoles per 24 hours or with ventricular arrhythmias III or a higher Lown class. The authors revealed a statistically significant drop of ventricular extrasystoles and a significant reduction of arrhythmias class IV of Lown's classification with a general shift of arrhythmias to lower classes. Improvement by at least one class occurred in 63%, deterioration without clinical impact in 11%. The drug does not have a clinical effect on haemodynamics. Side-effects of an anticholinergic type were recorded in 13% and a toxic allergic exanthema was observed in 6.5%. Tiracizine extends the spectrum of membrane antiarrhythmic drugs. Its effectiveness is similar as that of propafenon. PMID- 8212609 TI - [Significance of the stress score in patients with coronary artery disease]. AB - The authors tested the importance of the load score for assessment of the prognosis of patients after myocardial infarction and for assessment of the severity of the atherosclerotic affection of the coronary arteries. The score is a numerical value calculated from data assembled during evaluation of bicycle ergometry according to the following formula: total duration of the load-(5X deviation of ST)-(4X anginous index). The value of the load score was retrospectively tested in a group of 31 patients after myocardial infarction (mean age 58.1 years), who died during the subsequent five years, and in 64 subjects, mean age 50.1 years, who were subjected to coronarography. The value of the load score in 77.4% of the group who died was less than -10. In the group of patients subjected to coronarography where three arteries or the trunk of the left coronary artery was affected the score in 81.8% of the patients was smaller than -10. The authors proved a close correlation between the value of the load score and the severity of affection of the coronary arteries. Therefore the load score can be used as one of the factors when selecting patients for coronarographic examination and revascularization of the heart muscle. The lead score helps also in the estimation of the prognosis after myocardial infarction. PMID- 8212610 TI - [Immunoglobulin E and acute myocardial infarct]. AB - The authors examined repeatedly the immunoglobulin E (IgE) and immunoglobulin G (IgG) level in patients hospitalized on account of acute myocardial infarction (AMI). In a group of 33 patients aged 40-59 years (25 men, and 8 women) the authors investigated the case-history for hay fever, allergic rhinitis, eczema, allergy to grass, sensitizing household dust or domestic animals. The authors assessed also the presence of asthma and eczema in parents or relatives. Furthermore the authors investigated the relationship of different components of the immunological profile in relation to IgE and AMI. They found that in AMI the IgE serum level rises or is high on the 5th day after acute myocardial ischaemia. On the 10th and 21st day of hospitalization the IgE level declined and by the end of the third week it was close to baseline values of 300 U/ml or less. The IgG level displayed an almost indirect relation, i.e. during the first days it was close to the borderline of normal values, while it increased significantly on the 21st day of hospitalization. The rise of the IgG level is a response of the immune system to recovery of the necrotic myocardial mass. Consistent with some authors abroad, the authors found that patients with AMI with a high initial IgE serum level have a better prognosis quo ad vitam. PMID- 8212611 TI - [Long-term study of glucose tolerance in individuals with a suspected diagnosis of diabetes]. AB - The authors evaluated the results of the long-term monitoring of the glucose tolerance in 90 subjects, 40 men and 50 women, who were referred to a diabetological clinic as suspect diabetics. The mean age during the initial examination was 55.7 years (mean 55.7 +/- 12.5), a diabetic family--history was recorded in 60% of the patients, obesity in 61%. The monitoring proceeded on average for 8.5 years (mean 8.5 +/- 6.8). During the baseline examination diabetes was detected only in three subjects (3.3%), in 41 (45.6%) impaired glucose tolerance was revealed which in the course of 18 years developed in 28 into diabetes. In 32 examined subjects (35.6%) the oral glucose tolerance test (oGTT) was repeatedly normal, however, 9 subjects developed in the course of 23 years diabetes, although the stage of impaired glucose tolerance was not recorded. oGGT in 11 patients (12.2%) was variable in the course of the follow up, normal glucose tolerance alternated with impaired glucose tolerance. In three subjects (3.3%) repeated examinations are consistent with renal glycosuria. From the results ensues that subjects suspect of diabetes with a marked family-history of diabetes and who are moreover obese it is important to ensure monitoring on a long-term basis as positivity during the initial examination is low (3.3%), while during long-term follow up the prevalence of diabetes is 54%. In patients with an impaired glucose tolerance there is a high risk of the development of diabetes, although the stage of impaired glucose tolerance is not always detected. PMID- 8212612 TI - [Free oxygen radicals in patients with diabetes mellitus]. AB - Free oxygen radicals (FOR) are one of the factors which participate via lipoperoxides in the development of atherosclerosis. Atherosclerosis complications affect a large part of diabetic patients. The objective of the present work was to test whether in diabetic patients there is, as compared with healthy subjects, a difference in the FOR activity and in the lipoperoxide blood level. A total of 30 patients with insulin non-dependent diabetes and a control group of 31 healthy subjects were examined. The FOR formation in blood, the concentration of malondialdehyde (MDA) as a marker of lipid paroxidation and serum lipid concentrations were assessed. In patients with diabetes a statistically significant increase in the FOR formation in blood (p < 0.01) and an increased MDA serum concentration (p < 0.01) were found. The mean serum lipid concentrations in the two groups did not differ significantly. The results suggest a significant participation role of highly reactive oxygen species in the development of vascular atherosclerosis complications. PMID- 8212613 TI - [Experience with sulodexide (Vessel Due F) in diabetics with ischemic disease of the lower extremities]. AB - A total of nine patients with diabetes type I and II and with claudications due to macro- and microangiopathies of the lower extremities took sulodexide (Vessel Due F) by the i.m. route for a period of 20 days and then as capsules for 90 days. In all a favourable therapeutic effect was recorded, in particular as regards delay of claudications. The authors recorded lower blood sugar values, lower levels of cholesterol, triglycerides, fibrinogen and plasma viscosity. In the authors' view sulodexide is an important advance in the treatment of diabetics with claudications. PMID- 8212614 TI - [Helicobacter pylori in patients with diabetes mellitus]. AB - The authors assessed the frequency of Helicobacter pylori in diabetic patients with gastroduodenal ulceration and non-ulcerative dyspepsia. They evaluated a group of 91 hospitalized type II diabetics which non-ulcerative dyspepsia, endoscopically confirmed ulceration of the duodenal bulbus and gastric ulceration. The control group was formed by 98 hospitalized non-diabetic subjects. Between the two groups there was no difference in the frequency of Helicobacter pylori in non-ulcerative dyspepsia (61.1% as compared with 56.0% in non-diabetics) and gastric ulceration (75.0% as compared with 77.7% in non diabetics). There is a significantly (p > 0.005) lower incidence of HP infection in diabetics with active duodenal ulceration (46.6%), as compared with non diabetics (87.5%). The authors assume that active duodenal ulceration in diabetics could be more frequently caused by other factors than Helicobacter pylori. PMID- 8212615 TI - [Atrophy of the gastric mucosa and Helicobacter pylori]. AB - The authors investigated the prevalence of Helicobacter pylori (H. p.) in atrophic gastritis in the antrum and/or in the corpus of the stomach (groups I IV), as compared with mucosae without atrophy. Criteria for elimination were age under 50 years, a case-history of the use of antibiotics during the last 6 months and chronic ingestion of alcoholic beverages. Group IV was formed by probands with pernicious anaemia who were divided into sub-group IVa with atrophy of the corpus and sub-group IVb with atrophy of the corpus and antrum. It was revealed that in probands with pernicious anaemia the presence of H. p. is significantly reduced (p < 0.01) when atrophy was present not only in the corpus but also in the antrum. The authors concluded that atrophic changes in the corpus only do not have a significant effect on the presence of H. p. in the antrum. The presence of H. p. is significantly influenced in a negative sense only when atrophic changes, in particular total atrophy, affect the antral mucosa. PMID- 8212616 TI - [Primary pulmonary hypertension]. AB - The authors describe a case of primary pulmonary hypertension from the onset of subjective complaints to terminal dextrolateral cardiac failure. They give an account of an unsuccessful attempt to influence the haemodynamics in this female patient by calcium channel blockers. In the discussion they deal briefly with contemporary knowledge and treatment of primary pulmonary hypertension. PMID- 8212617 TI - [New examining technics and approaches in ultrasonography]. AB - The new examination technique and methods are causing a fundamental development in ultrasonic diagnostics. The author describes the characteristic features of new technique and methods, e.g. endosonography, peroperative sonography, computer processing of ultrasonographic images of the liver, coloured picturing of abdominal vessels by the 2-D-Doppler method in real-time, 3-D ultrasonic diagnostic and application of contrast agents in ultrasonography. All said methods require adequate erudition of the examiners and high standard instrumental equipment. They indicate wide prospects of development in ultrasonographic diagnostics in the nineties. PMID- 8212619 TI - [The Saint Vincent Declaration--a call to increase care of diabetics. IV. Diabetic retinopathy]. PMID- 8212618 TI - [Mechanisms of erythrocyte sedimentation. Do we know more today than Robin Fahraeus?]. AB - The authors analyze in detail all substantial factors which influence the red cell sedimentation. They express this one a function of time, hematocrit, hemoglobin concentration, concentration of some plasma proteins, citrate density and viscosity. These values serve to describe the plasma and red cell density, plasma viscosity, red cell aggregation and to express the influence of the hematocrit on the red cell sedimentation. The authors try to quantify all influences in order to differentiate important factors from less important ones. Finally they demonstrate on several case-histories the necessity of a rational analytical attitude to values of the red cell sedimentation rate. PMID- 8212620 TI - [Ultrasonography of the kidneys for the detection of incipient diabetic nephropathy]. AB - At the First Medical Clinic of the Faculty Hospital in Prague 5 Motol a group of 15 men and 14 women treated on account of type I diabetes for a mean period of 12.8 +/- 5.8 years was examined. Their mean age was 26.3 +/- 5.8 years and their BMI 23.91 +/- 2.82. The control group was formed by 18 healthy subjects (10 men and 8 women) mean age 23.8 +/- 8.9 years, BMI 22.44 +/- 2.48. All subjects were subjected to a detailed ultrasonographic examination and, assessment of microalbuminuria. From the assembled sonomorphometric data the volume of the right kidney was related to the BMI and thus the renal volume index (RVI) was obtained. In the group of diabetic subjects a statistically significant correlation was found between RVI and microalbuminuria (r = 0.574, p < 0.01). In the group of patients with RVI higher than 7.44 a close correlation was found between microalbuminuria and RVI (r = 0.993, p < 0.05). In the group of patients with a duration of diabetes under 5 years no correlation between the investigated parameters and the RVI was found, nor a mutual correlation of parameters. In patients with diabetes persisting for 5-20 years correlation was found between microalbuminuria and RVI (r = 0.686, p < 0.01). In the group of patients with diabetes for more than 20 years there was no correlation between RVI and other indicators. PMID- 8212621 TI - [Modelling the kinetics of C-peptide and hepatic extraction of insulin (in type 2 diabetics and non-diabetics with hypertriacylglycerolemia)]. AB - Increased glucose release from the liver which is responsible to a considerable extent for fasting hyperglycaemia in type 2 diabetics is associated with hepatic insulin resistance. Assessment of insulin extraction in the liver can therefore be useful in investigations of all pathophysiological conditions with deviations of glucose tolerance, or in the course of insulin secretion. The control group was formed by 8 healthy men, mean age 43.6 +/- 5.9 years, mean BMI 24.7 +/- 2.8. The authors examined also a group of 7 men with diabetes mellitus type II, mean age 46.7 +/- 5.9 years, BMI 31.4 +/- 8.9 and 6 men with hypertriacylglycerolaemia, mean age 44.2 +/- 3.1 years and mean BMI 26.2 +/- 1.4. All were examined by the intravenous glucose tolerance test with frequent blood sampling. In every sample the blood sugar level, insulin level and C-peptide level were assessed. The data were evaluated and the "hepatic insulin extraction index" was thus obtained. The "hepatic insulin extraction index" was significantly lower in type 2 diabetics throughout the experimental period (0-180 min.) as well as during individual intervals evaluated (0-20 min. and 20-180 min.). In subjects with hypertriacylglycerolaemia this index was lower only during the 0-20 min. interval. Changes of the "hepatic insulin extraction index" in patients with hypertriacylglycerolaemia do not reach the intensity recorded in diabetics and may thus indicate a milder grade of hepatic insulin resistance. PMID- 8212622 TI - [Reaven's metabolic syndrome X in the families of individuals with premature cerebrovascular attacks]. AB - In families of subjects with premature ischaemic cerebrovascular attacks (a total of 45 families with 190 members) the authors detected a high incidence of dyslipidaemia, arterial hypertension, impaired glucose tolerance and non-insulin dependent diabetes mellitus, frequently with striking cumulation. The authors investigated therefore the relationship of the insulin level as an indirect reflection of insulin resistance with these risk factors. The fasting insulin levels correlated significantly positively with triglyceride levels, apolipoprotein B, atherogenic indices and negatively with HDL-cholesterol. The probands and siblings with arterial hypertension had significantly higher fasting insulin levels, as compared with subjects without hypertension which was due to a more frequent incidence of overweight. Patients with an impaired glucose tolerance and NIDDM had significantly higher fasting insulin levels and insulin levels after two hours (the latter value was not assessed in diabetes) and unfavourable "atherogenic" lipid and lipoprotein values, as compared with subjects without glucose intolerance and the control group. Overweight (BMI > 26) had an adverse impact on all investigated indicators of lipid and carbohydrate metabolism whereby a W/H ratio > 0.85 as a manifestation of central obesity further accentuated this adverse effect. The authors draw from these results therapeutic conclusions as regards the mentioned risk factors in these families. They emphasize the importance of non-pharmacological intervention of the metabolic X syndrome by weight reduction and more physical activity not only in families of subjects with early atherosclerosis but in the entire population which has a high prevalence of cardiovascular diseases. PMID- 8212623 TI - [Are central hemodynamics the decisive factor in the manifestation of chronic heart failure?]. AB - In the past some authors revealed that data assembled during examinations of the central haemodynamics, echocardiography, subjective complaints, physical findings and load tolerance in patients with chronic heart failure are not mutually consistent. The authors examined therefore comprehensively 40 patients with different grades of cardiac failure. They revealed very loose relations between the grade of functional classification, echocardiographic and invasive haemodynamic parameters at rest on the one hand and spiroergometric indicators on the other hand. Closer relations with spiroergometric findings were obtained with values of invasive haemodynamic parameters after a load, in particular values of the cardiac index, and systemic vascular resistance. The authors conclude that for clinical manifestations of chronic cardiac failure the peripheral circulation and tissue metabolism is at least equally important as changes of central haemodynamics. Moreover, the importance of the right ventricular function and diastolic cardiac function is not sufficiently appreciated. PMID- 8212625 TI - [Lipostat in the treatment of hyperlipoproteinemia]. AB - Within the framework of clinical tests of LIPOSTAT (pravastatin tablets 20 mg Bristol Meyers-Squibb Co.) this hypolipidaemic preparation was administered to 28 patients with different types of hyperlipoproteinaemias, mainly of type IIa. Administration for a period of four weeks--20 mg in the evening--had a significant effect on several basic indicators of the lipid metabolism. The total plasma cholesterol level declined by 20%, the apolipoprotein B level by 11%, the HDL cholesterol level rose by 38% and the triacylglycerol level declined by 18%. During administration the serum levels of aminotransferases, creatine kinase and alkaline phosphatase did not increase. No adverse side-effects were observed which called for discontinuation of treatment. Pravastatin is according to the authors' experience and the results of others an effective hypolipidaemic agent, suitable for the majority of patients with hyperlipoproteinaemias, in particular those with elevated plasma cholesterol levels. PMID- 8212624 TI - [Treatment of resistant forms of multiple myeloma using a combination of mitoxantrone, vincristine and prednisone (the NOP regimen)]. AB - In the submitted study the authors summarize experience with the treatment of resistant forms of multiple myeloma by a combination of Mitoxantrone, Vincristine and Prednisone (NOP regime). The above treatment produced an objective therapeutic response in 33% of the patients, in 50% a partial response, in 17% it failed. The median of survival in the whole group was 10.5 months. Substantially poorer therapeutic results were recorded in patients with primary resistance to the initial chemotherapy (objective response only in one of 6 patients) than in the group with secondary resistance which developed during a relapse of the disease (objective response in 3 of 6 patients). With the exception of marked leukopenia and neutropenia treatment by the NOP regime was very well tolerated. The NOP regime is an expedient approach which extends practical possibilities, in particular ambulatory treatment of refractory forms of multiple myeloma. PMID- 8212626 TI - [Cystic lymphangioma of the retroperitoneum]. AB - The authors present the case-history of a patient with a cystic retroperitoneal lymphangioma. Its diagnosis was established only by histological examination of the resected tissue. The authors draw attention to the symptomatology, diagnosis, therapy and discuss contemporary views regarding the cause of this disease. PMID- 8212627 TI - [An unusual cause of recurrent septic states]. AB - The authors describe the septic sequelae of an unobserved embolization of a central venous catheter into right-sided cardiac compartments. The finding of an embolized fragment of a catheter which was in the patient's circulation for 89 days was quite incidental. The previous period was associated with diagnostic doubts in various departments. The most frequent diagnosis of repeated septicaemia was bacterial endocarditis, although repeated echocardiographic examinations did not confirm it. Similarly, repeated X-rays did not contribute to the diagnosis--this can be explained by dilatation of the heart of the patient. Extraction of the embolized fragment by means of a catheter resolved the problem. The fragment was colonized by the causal agent of the febrile conditions- Staphylococcus aureus. PMID- 8212628 TI - [Treatment of the leukostasis syndrome in chronic lymphadenosis using leukapheresis]. AB - The authors draw attention to the leukostasis syndrome which develops in haematological patients in case of enormous leucocyte proliferation. It occurs most frequently in chronic myelosis but may occur also in other types of leukaemia. The diagnosis is not easy. Most frequently disorders of the microcirculation develop in the lungs and brain. These are frequently very urgent clinical situations which can be resolved by leukapheresis. The authors described a patient where during chronic lymphadenosis proliferation of lymphocytes occurred to values of 1432 x 10(9)/l. After leukapheresis and cytostatic treatment rapid improvement of the condition occurred and the leucocyte values were approximately 30 x 10(9)/l. The patient's condition improved for a long period of time and became stabilized. PMID- 8212629 TI - [Lyme disease in internal medicine]. AB - The authors present a review on the aetiology, clinical aspects, diagnosis and treatment of Lyme disease. They describe three patients who were treated in their department for Lyme disease. Although this disease has been followed up in Bohemia and Slovakia only for nine years, it is probable that it is more frequent than diagnosed. Lyme disease is a disease which affects different organs. Therefore it is important that specialists in internal medicine should more frequently consider the possible presence of this disease when making differential diagnoses. PMID- 8212630 TI - [Pharmacotherapy of diastolic dysfunction in heart failure]. AB - Impaired left ventricular diastolic function is an indicator of early stages of heart disease. In cardiac failure it is not necessarily associated with impaired systolic function and correlates more closely with clinical symptoms or load tolerance. Pharmacotherapy leading to improved diastolic parameters improves also the clinical condition of cardiac failure. Based on data in the literature, the authors analyze drugs which exert a favourable effect on left ventricular diastolic function: ACE inhibitors, calcium channel blockers, beta adrenergic agonists, phosphodiesterase inhibitors, diuretic and direct vasodilating agents, from the aspect of clinical administration. PMID- 8212631 TI - [The intestinal pseudo-obstruction syndrome]. AB - Intestinal pseudoobstruction is a syndrome characterized by manifestations and signs of intestinal obstruction without evidence of a lesion obstructing the intestinal lumen. It is divided into primary and secondary forms and into acute and chronic forms. Various diseases, incl. malignant tumours, can be manifested by this syndrome. In its therapy prokinetically acting preparations are used with a favourable effect of colonoscopic decompression. PMID- 8212632 TI - [Diagnosis of primary aldosteronism]. AB - Clinical observations in recent years indicate that primary aldosteronism (PA) comprises more subtypes than was originally assumed. The author presents a brief account of the contemporary classification of different forms of the disease. He discusses some recent aspects of the laboratory and morphological diagnosis of PA with regard to the possible differentiation of the most frequent two forms: aldosterone producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). In the conclusion the author mentions the differential diagnosis of PA. PMID- 8212633 TI - [Treatment of hypertension in kidney diseases]. AB - The authors review recent therapeutic procedures in arterial hypertension associated with renal disease. Treatment of hypertension is comprehensive, it comprises non-medicamentous procedures, pharmacotherapy and in some affections also interventional and surgical therapy. Effective reduction of the blood pressure to values < or = 140/90 mmHg unequivocally retards progression of renal disease, the development of nephrosclerosis and delays the development of renal insufficiency. In medicamentous treatment of nephrogenic hypertension a wide range of conventional antihypertensive drugs is used. Their selection and dosage must be adapted to the type of the basic renal disease and the reduction of renal functions. Recently the demand has been raised that the antihypertensive drugs used should possess in addition to the blood pressure lowering effect also an additive renoprotective effect ensuing above all from diminished intraglomerular hypertension and undesirable hyperfiltration, a changed permeability of capillary membranes due to reduction of microalbuminuria and proteinuria or restriction of proliferation procedures. These demands are met by the angiotensin I-converting enzyme (ACEI) inhibitor. If the correct dosage is used, ACEI are, due to their excellent antihypertensive action, absence of undesirable metabolic sequelae and significant renoprotective effect, drugs of the first line in nephrogenic hypertension. The authors use above all ACEI with a long-term effect, i.e. those without a SH group in the molecule. Very small doses (e.g. 2.5 mg Enalapril per day) reduce microalbuminuria and proteinuria and retard progression of nephrosclerosis also in nephropathies without systemic hypertension, e.g. in diabetic glomerulosclerosis. The renoprotective effect is manifested more markedly in initial stages of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212634 TI - [Damage caused by monoclonal immunoglobulins and possibilities of therapy. 1]. AB - Pathological clones of plasma cells produce monoclonal immunoglobulins (M-Ig), either the entire molecule or only light chains. These proteins lead in the organism to various pathological process. The increased blood viscosity causes eyesight damage. Impaired coagulation or haemolysis caused by cold agglutinins are frequent. Depending on the orientation of the antigenic determinant of M-Ig, nervous and muscular structures suffer damage, as well as the kidney; metabolic disorders, hypoglycaemia or endocrinopathies may develop. Some of the mentioned disorders are readily diagnosed, some can be detected only by an aimed examination. The presented review should help early diagnosis of these pathological processes. PMID- 8212635 TI - [The Saint Vicent Declaration--a call to increased care of diabetics. V. Ischemic heart disease--ICHS in diabetics]. PMID- 8212636 TI - [The hypertensive metabolic syndrome]. AB - Systemic arterial hypertension is not merely a simple haemodynamic abnormality. It is as frequently as in 80% associated with metabolic deviations such as impaired glucose tolerance or NIDDM, obesity, hyperuricaemia, hyperlipoproteinaemia, rapid development of atherosclerosis. This cluster of different symptoms with higher BP readings is too frequent to be incidental. We speak therefore of hypertensive metabolic syndrome which is close to or identical with Reaven's syndrome X or familial dyslipidaemic hypertension. The common pathogenetic basis of the listed metabolic deviations and hypertension is probably genetic or acquired reduction of tissue sensitivity, in particular striated muscle sensitivity to the physiological action of insulin. The consequence of this insulin resistance and the effort to maintain euglycaemia is a compensating adaptational risk of plasma insulin. Hyperinsulinism in addition to an increased synthesis of triacylglycerols, VLDL and LDL lipoproteins can promote the rise of BP by a complex mechanism: it stimulates the activity of the sympathetic nervous system, it promotes sodium retention in the kidneys, it affects transmembrane transport mechanisms for electrolytes and an increase of intracellular sodium and calcium, it stimulates hypertrophy and remodelling of the vascular wall and hastens the development of atherosclerosis. Hyperinsulinaemia is also associated with resistance of hypertonic patients to antihypertensive treatment. Its reduction by non-pharmacological procedures (reduction of body weight, physical activity etc.) restore the effectiveness of antihypertensive drugs. Insulin resistance is most probably a genetically conditioned abnormality which has multiple phenotypic manifestations, depending how this congenital disposition is amplified or associated with other genetic abnormalties or external and internal factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212637 TI - [Non-invasive programmed transthoracic ventricular stimulation]. AB - In 10 healthy volunteers programmed transthoracic stimulation of the ventricles was performed using two commercially available non-invasive pacemakers. The connection of the oesophageal stimulator SP-5 with the transthoracic ventricular stimulator NP-4D made it possible to obtain a two-lead ECG tracing without artefacts. The quality of the obtained tracings (surface tracing and oesophageal tracing) made it possible to assess accurately the ventriculo-atrial conduction. The examinations performed indicate the practical use of combined oesophageal and transthoracic stimulation during non-invasive diagnosis. PMID- 8212638 TI - [Evaluation of physical rehabilitation in myocardial revascularization using echocardiography]. AB - The authors investigated 155 patients, mean age 50.6 years, after revascularization of the myocardium. The group was divided at random into a group with a high intensity of physical rehabilitation (A) and a medium and low rehabilitation group (B). The rehabilitation programme comprised physical exercise at least three times per week for at least 30 mins. with a dynamic load up to 80% of the maximum heart rate in group A and up to 40% in group B. The mean initial haemodynamic indicators in both groups were equal (LVEDP 17.5 mm Hg and 16.5 resp. and EF 52.3% and 50.5% resp. in group A and B). Six months after revascularization the mean values of work tolerance increased in group A more than in group B (58.6 kJ, as compared with 44.2 kJ) and this difference is even greater after three years (70.4 kJ as compared with 51.5 kJ). The mean values of the ejection fraction (EF) at rest do not differ in the two groups after 6 months nor after 3 years (51.3% in group A, as compared with 54.6% in group B after 6 months, and 55.2% vs. 53.7% resp. after three years). The EF after a dynamic load after 6 months and 3 years does not differ in the two groups either (57.2% vs. 56.4% after 6 months and 55.1% vs. 54.5% after three years). Similar results were also obtained on evaluation of the mobility index of the walls at rest and after a dynamic load.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212639 TI - [Comparison of the effects of molsidomine retard and isosorbide dinitrate retard in patients with stable angina pectoris using an ergometry test]. AB - In 24 men with angina after exertion the authors assessed, using ergometry, the action of molsidomine retard and isosorbide dinitrate retard after a single dose and after tree-week administration of the drug. The authors found that 8 mg of molsidomine retard in a single dose had a somewhat more potent effect than 40 mg isosorbide dinitrate retard. After prolonged administration the effect of both drugs on haemodynamics diminished and in molsidomine a significant decline of action was observed before development of a reduced S-T segment on the ECG. After three weeks' administration the effects of both drugs were comparable. After neither drug clinically significant tolerance developed when the drug was administered every 8 hours. In the conclusion the authors discuss possible mechanisms involved in development of tolerance. PMID- 8212640 TI - [Bisoprolol in the treatment of hypertension]. AB - Bisoprolol is an effective antihypertensive drug which reduces significantly the systolic, and diastolic blood pressure, the pulse rate in a recumbent, sitting and standing position. Recommended dosage is 10-15 mg once a day. Bisoprolol is suitable for use in hypertensive patients with associated diseases, in particular angina pectoris and impaired rhythm. PMID- 8212641 TI - [The significance of plasminogen activator inhibitor 2 in patients with hematologic malignancies]. AB - The authors investigated the incidence of the plasminogen activator inhibitor-2 (PAI-2) in 88 patients with haematological tumours. In four patients (4.5%) an elevated PAI-2 level was found: in patient (no. 1) with non-differentiated leukaemia which developed as a result of transformation of myelodysplastic syndrome, in a female patient (no. 2) with non-differentiated blastic crisis of chronic myeloid leukaemia, in a female patient (no. 3) with acute monocytic leukaemia (M5) and in a pregnant female (patient no. 4) with a malignant lymphogranuloma. In none of the other patients with another type of acute myeloid leukaemia or other haematological tumours PAI-2 was detected. High PAI-2 levels after successful cytostatic treatment and attainment of complete remission reached normal levels, during a relapse high PAI-2 levels were recorded again. The authors assume that the presence of PAI-2 may suggest a monocytic origin of the cells which produce it. They conclude also that its value may reflect the activity of the disease with high levels during presentation or relapse of the disease and a drop or disappearance of PAI-2 after successful treatment and achieved remission. PMID- 8212642 TI - [Do we have a sufficient supply of anti-HLA serum? Review of sera produced by the transfusion service 1974-1992]. AB - In 1974-1992 in the HLA reference laboratory of the Institute of Haematology and Blood Transfusion in Prague 15,731 sera sent by transfusion departments were examined; 4368 sera met the standard required for HLA typing, detecting 9 HLA-A, 18 HLA-B and 3 HLA-C antigens. Against these antigens with the exception of HLA B41 and public antigens HLA-Bw4 and HLA-Bw6 monospecific sera were found: against 15 HLA antigens in a large number and against 12 HLA antigens--2 to 21 for the given antigen. Sera against subtypes of HLA antigens were sought only in rare instances, as in common practice it is sufficient (and sometimes essential) to type only basic HLA antigens. PMID- 8212643 TI - [Is undirected liver biopsy a safe procedure?]. AB - In the authors' group of 976 umaimed liver biopsies (ULB) 10 complications were recorded. The authors described them and compared them with reports from the world literature. Two patients from the group died after ULB. One as a result of biopsy from haemoperitoneum, the other patient died with delirium tremens after surgery called for by persisting peritoneal syndrome. In eight patients mild complications were involved. In five patients complications receded spontaneously, in three after administration of an analgetic. From the submitted paper ensues that ULB is not quite safe, even when used by an experienced physician and when all contraindications are respected. A smooth course is not ensured by a risk-free diagnosis, previous uncomplicated biopsies normal prebioptic haemocoagulation tests. It is essential to realize this with regard to every patient where we indicate ULB. It is better to omit it unless we are unequivocally convinced of its asset. The question thus is: What will be the benefit of ULB for the patient? PMID- 8212644 TI - [Protective special shoes for diabetics. Personal experience with a group of high risk diabetics during a 2 and 1/2 year period]. AB - A group of 60 type II diabetics with the risk of development of ulceration of the feet was provided with protective specialized footwear. In the course of 2.5 years in 45 patients who could be evaluated the frequency of relapses of previous ulcerations, the development of first ulcerations and the effect on indicators of immediate high risk of a defect (formation of decubital ulcers, blisters) was investigated, as well as the general biomechanical comfort. In 10 patients with relapsing defects relapses developed twice (20%), no primary ulceration developed. As compared with common footwear, the protective footwear had a favourable effect on the formation of sores and blisters 25 patients (55.5%/ 45/100%) reported improvement of the general comfort when walking. 28 (62.2%) patients make use of the favourable experience with the specialized footwear when selecting shoes or when modifiying standard footwear. A surprising finding was delayed fatigue when walking reported by 35 (77.8%) patients, mitigation of dysaesthesias by 23 (51%), pain in the joints by 14 (31.1%), improved stability by 35 (77.8%) of the patients. With regard of the improvement of some subjective complaints the use of protective footwear can be considered a symptomatic therapeutic element. According to clinical results specialized footwear has a favourable and protective effect on already damaged feet with a reduced tolerance for combined (mechanical, ischaemic, neurotrophic, infectious) insults. Consistent with data of authors from abroad after a 2-5-year follow-up there was a cca 50% reduction in the number of relapses of ulcerations and amputations as compared with common not modified footwear. PMID- 8212645 TI - [Lymph node enlargement in hairy cell leukemia and problems with significant abdominal lymphadenopathy]. AB - Enlargement of nodes in leukaemia with hairy cells (LVB) during the initial examination is rarely encountered. In the final stage of the disease it was found in six of our ten patients. A special situation is marked enlargement of retroperitoneal nodes observed in two patients. In one of them the nodes diminished after irradiation, in the second patient irradiation was not possible because of severe pancytopenia. Treatment with alpha-interferon failed previously in this patient. The question remains whether marked enlargement of the abdominal nodes is part of the picture of the disease or whether it is the manifestation of transformation of the disease into a more acute type. The authors recommend examination of the abdominal nodes by means of computed tomography (CT) already during the initial examination and during the subsequent course of the disease, in particular when there are signs of relapse. PMID- 8212646 TI - [To what extent is it possible to noninvasively determine left ventricular diastolic function in patients with ischemic heart disease using doppler echocardiography?]. AB - The author discusses possibilities of non-invasive assessment of left ventricular diastolic function in patients with ischaemic heart disease, using Doppler echocardiography with visualization of left ventricular diastolic filling. Attention is drawn to the fact that left ventricular filling is a very complicated process which depends not only on the diastolic function of the left ventricle but also on the given haemodynamic state of the patient and on other factors; this must be taken into account when interpreting Doppler filling curves. The author concludes that during gradual development of left ventricular dysfunction non-linear changes occur of the filling flow parameters of the left ventricle and therefore they are not suited for quantitative assessment of diastolic dysfunction of the left ventricle. The value of Doppler echocardiography for evaluation of the diastolic function of the left ventricle may be above all assessment of early disorders and the non-invasive estimate of high left ventricular filling pressures. PMID- 8212647 TI - [Diuretics in the treatment of hypertension]. AB - Diuretics are one of the basic groups of antihypertensive drugs. They have also certain limitations and undesirable effects which are better defined than in other more recently developed antihypertensives. Undesirable effects can be prevented by early combination of saluretics with K+ sparing diuretics or other antihypertensive drugs and by prevention of metabolic disorders (in particular insulin resistance and dyslipoproteinaemia) and by prescription of small doses. Only prospective intervention studies will show whether the advantages of other groups of antihypertensives, as compared with diuretics, will influence the prognosis of patients with essential hypertension in a substantial way. Several studies along these lines are under way. PMID- 8212648 TI - [Mechanisms of the beneficial effect of indomethacin and nimodipine in the treatment of traumatic shock in rats]. AB - Aiming to study the pathogenetic mechanisms of the disturbed function of the central nervous system in traumatic shock we have determined the dynamics of changes of eicosanoids (PGF2 alpha, TxB2, 6-keto-PGF1 alpha, peptidoleukotrienes) in the brain structures (medulla oblongata, hypothalamus) of the experimental animals subjected to bilateral trauma of the hind legs (tourniquet trauma, LD50). Considering that our previous data have shown the importance of eicosanoid mediatory system in the pathogenetic mechanisms of shock, we have studied possible use of prostaglandin synthesis inhibitors (indomethacin) and calcium channel antagonists (nimidipine) in traumatic shock. The authors have concluded that in the pathogenetic mechanism of the disturbed function of the CNS in traumatic shock the important role has peptidoleukotrienes as well as that the combined use of prostaglandin synthesis inhibitors and antagonists of voltage dependent calcium channel would be useful in the therapy of the injured patients. PMID- 8212649 TI - [Comparative study of generation of active forms of oxygen in blood leukocytes and alveolar macrophages in patients with bronchial asthma]. AB - The aim of the study was to perform comparative simultaneous study of generation of active forms of oxygen by blood leukocytes (GAFBL) and generation of active forms of oxygen (GAFO) by alveolar macrophages (AM) and to evaluate their contribution in development of bronchial asthma. The study comprised 25 subjects: 10 with bronchial asthma, 10 with chronic bronchitis and 5 healthy subjects. GAFO AM and GAFBL were examined by method of luminol-dependent chemiluminescence (CL). The basal and stimulated CL parameters as well as the relationship of GAFBL and GAFO AM were measured. In the phase of deterioration, both CL parameters, GAFBL and GAFO AM were markedly increased in patients with bronchial asthma compared to normal subjects. However, in healthy subjects and in patients with bronchial asthma both CL parameters of GAFBL were markedly increased than the analogous parameters of AM. The relationship of GAFBL and GAFO AM for both parameters in patients with bronchial asthma was lower than in healthy subjects which prove AM to be more active than blood leukocytes. In patients with chronic bronchitis both CL parameters of GAFO AM were markedly increased than in healthy subjects and only the stimulated CL parameters of GAFBL were lower than in patients with bronchial asthma. However, the relationship of GAFBL and GAFO AM for the basal CL parameters practically do not differ from the normal which suggests the larger activity of blood leukocytes compared to AM activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212650 TI - [Antibiotic prophylaxis in elective colorectal surgery]. AB - The prospective clinical examination of 80 patients with the verified carcinoma of the colon and rectum was performed at the Clinic of General and Vascular Surgery of the M.M.A. in the period 1989-1990 with the aim to evaluate efficacy and justified use of antibiotic prophylaxis or prophylaxis and antibiotic therapy after elective surgical intervention. The preoperative mechanical preparation was performed in all patients. The combined metranidazole-gentamycin therapy was applied. In the group of patients receiving antibiotic therapy only, as a short prophylaxis, the postoperative infective complications were recorded in 5% of cases. In the second group of patients receiving antibiotic prophylaxis and therapy these complications were recorded in 10% of cases. The average duration of postoperative hospitalization was 13/14 days in both groups of patients. The use of antibiotic prophylaxis in elective colorectal surgery in patients with carcinoma of the colon and rectum is justified but it is not a substitution for nonadequate surgical intervention. PMID- 8212651 TI - [Diagnostic arthroscopy of the knee and its use in meniscus surgery]. AB - The results of 1000 diagnostic knee arthroscopies are presented. The clinical diagnosis of meniscus tear was established in 740 (74%) patients. This diagnosis was arthroscopically confirmed in 431 (58.2%) patients only. Other pathologic states of the knee were clinically diagnosed in 260 (26%) patients. In this group of patients the meniscus tear was found by arthroscopy in 41 (15.7%) patients. Complications developed in 11 (1.1T%) of all operated patients. PMID- 8212652 TI - [Surgical treatment of paralytic convergent strabismus using a modification of Jensen's method]. AB - Surgical treatment of paralytic convergent strabismus using the modified Jensen's is method was performed in 35 patients. The full success (orthophoria) was achieved in 51.5% and satisfying (approximately orthophoria) in 25.7% of cases. The six-year follow up of patients showed that surgical effect was permanent in 71.4% of cases. The most common cause of paralytic convergent strabismus has been trauma (71.4%), and, that, traffic accidents in 45.7%. According to communications and available literature this modified treatment of paralytic convergent strabismus for the first time in Yugoslavia has been applied in the Military Medical Academy. PMID- 8212653 TI - [Changes in thyroid hormone levels in patients with acute viral hepatitis]. AB - In 10 patients with acute viral hepatitis A or B the dynamics of the concentrations of the thyroid hormones thyroxine (T4), triiodothyroxine (T3) and their coefficient T3/T4, and thyroid stimulating hormone (TSH) in all phases of hepatitis have been studied. In acute phase and in the fully developed clinical picture of the diseases, the increased T4 values and decreased values of T3, T3/T4 coefficient and TSH were found. These changes are explained by the slowed down deiodinization of T3 and T4 in hepatocytes as well as by the disturbed secretion of the thyroid hormone in hepatitis and they could be of some value in diagnosis and prognosis. PMID- 8212654 TI - [Comparison of gas chromatography with headspace injectors, the Aull-McCord chemical method and the Alcotest ethylometer in the determination of blood alcohol]. AB - Gas chromatography has been more commonly used in determination of alcohol in blood and other biologic fluids as the most precise and reliable method. Using this method as the standard one, the comparison was made of the results obtained by the analysis of the same samples using the chemical method by Aullu and McCord and results obtained by alcotest ethylmeters 7010, 7110 and 7310. The high correlation was achieved by comparing gas chromatography and chemical method (r = 0.92 and n = 29), that is, etyhlmeters. The best agreement of results was achieved with the alcohol concentration 0.0 mmol/l- 21.7 mmol/l. PMID- 8212655 TI - [Pseudothrombocytes in acute leukemias]. AB - Pseudoplatelets are the cytoplasmic fragments in the size of platelets originated not from megakaryocytes but from other blood cells which were observed in some patients with leukemia and infection. The clinical importance of pseudoplatelets is manifested in the falsely increased number of platelets in these patients. Transmission electron microscopy was used in the cytologic examination of 23 patients with different types of acute leukemia. The presence of pseudoplatelets in the form of budding of the cytoplasm of the granulocytic, monocytic and lymphocytic strains of various maturity has been shown. PMID- 8212656 TI - [Depressive syndromes]. PMID- 8212657 TI - [AIDS throughout the world and possibilities of preventing the spread of HIV infection]. PMID- 8212658 TI - [Serum iron and glucose and colonization of the oral cavity with Candida species in soldiers]. PMID- 8212659 TI - [The importance of the dipyridamole stress test in the diagnosis of ischemic heart disease]. PMID- 8212660 TI - [The chronic fatigue syndrome associated with Epstein-Barr virus infection]. PMID- 8212661 TI - [A rare manifestation of benign mediastinal teratoma]. PMID- 8212662 TI - [The work of the Serbian Volunteer Medical Service Division in Dobrudza]. PMID- 8212663 TI - Prevalence of platelet transfusion reactions before and after implementation of leukocyte-depleted platelet concentrates by filtration. AB - To determine the impact of platelet leukodepletion by filtration on the overall prevalence of reported transfusion reactions associated with platelet concentrates, we audited platelet transfusion reactions after infusion of platelet concentrates reported at University Hospitals of Cleveland over 6 months before (interval 1, July 1, 1989 to December 31, 1989) and after (interval 2, July 1, 1990 to December 31, 1990) implementation of the Pall PL 50 filter on our adult Hematology-Oncology inpatient unit (Division 60). Thirty-two (1.7%) of 1,901 random, pooled platelet transfusion events resulted in blood bank transfusion reaction workups in interval 1, compared to 90 (5.3%) of 1,704 in interval 2 (p < 0.001). The Division 60 service accounted for more of our hospital-wide platelet reactions after implementation of the filter in interval 2 (84%) than before filtration in interval 1 (42%), p = 0.002. The prevalence of reaction workups for Division 60 was 0.6% for interval 1, compared to 4.3% for interval 2 (p < 0.001). No differences were found between interval 1 and interval 2 for the rate of discontinuation of platelet transfusion (36 vs. 32%, p = 0.14), rate of premedication for platelet transfusion (72 vs. 65%, p = 0.6), percentage of direct antiglobulin test-positive reactions (17 vs. 5.4%, p = 0.09), percentage showing icteric/hemolyzed serum (15 vs. 4.4%, p = 0.09), or reactions believed to be due to red blood cell incompatibility (8.8 vs. 1.1%, p = 0.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212664 TI - Serological screening, using three different test systems of platelet-transfused patients with hematologic-oncologic disorders. AB - Sera of hematologic-oncologic patients were tested regularly after platelet transfusions in three test systems: lymphocytotoxicity test, platelet adhesion immunofluorescence test, and--only selected sera--in the monoclonal antibody specific immobilization of platelet antigen test. Of 388 patients 53 (14%) had HLA antibodies 5 of these in combination with platelet-specific alloantibodies. Lymphocyte-restricted (non-HLA) reactions were observed in 20 patients, the majority of which was attributed to lymphocyte-specific auto- or alloantibodies. Sera of 27 patients showed platelet-specific reactions, usually cold-reacting autoantibodies which have no effect in vivo. PMID- 8212665 TI - HIV transmission by seronegative blood components: report of 2 probable cases. AB - HIV seroconversion was reported in 2 haemophiliacs after having corrective orthopaedic surgery. They received solvent-detergent/heat-treated factor VIII concentrate, HIV-seronegative cryoprecipitate and fresh frozen plasma during the course of surgery. HIV seroconversion was found on days 31 and 71 after surgery. It is highly probable that the infections were acquired by transfusions of seronegative blood components. In countries with a relatively low prevalence of HIV infection, transmission of HIV by transfusion of derivatives of seronegative blood is occasionally reported as a rare complication of blood transfusion [1-3]. In Thailand the prevalence of HIV infection and the incidence of new infections in the general population and in blood donors has recently increased dramatically (fig. 1) [4-5]. As a result of these components prepared from HIV-seronegative blood donations pose a significant hazard to recipients because of the risk of viraemia during the 'window period' of HIV infection. Here we report HIV infection in 2 haemophilia patients treated with HIV-seronegative (using Fujirebio agglutination or second-generation Abbott ELISA) cryoprecipitate and fresh frozen plasma in 1991, prepared locally from single-unit donations. All donors were voluntary. Anti-HIV was tested in every unit of donor blood before processing to blood components. Although not proven, it is highly probable that the infections were acquired by transfusions of seronegative blood components. PMID- 8212667 TI - Improved removal of anti-A and anti-B antibodies from plasma using blood-group active haptens. AB - Highly efficient anti-blood group A and B immunoadsorbents for extracorporeal treatment were developed by immobilizing A and B trisaccharide and A tetrasaccharide haptens on Sepharose 4FF and Fractogel TSK using three different methods. The adsorption of the IgG and IgM anti-A antibodies was essentially the same regardless of the A hapten used or the method of oligosaccharide coupling. The adsorption of IgM anti-A was found to be more sensitive than IgG anti-A to changes in column flow rate. The binding of both the IgM and IgG antibodies was slightly lower at 37 degrees C than at 22 degrees C. An anti-A/anti-B adsorbent column potentially suitable for treatment of patients was prepared. A column switching system resulted in a more efficient adsorption of antibodies. Hapten leakage from the column was very low. No nonspecific adsorption of plasma proteins to the column (other than traces of albumin) could be detected. PMID- 8212666 TI - Comparison of three different immunoassays and PCR for the detection of hepatitis C virus infection in pregnant women in Taiwan. AB - To compare different hepatitis C virus (HCV) immunoassays and HCV-RNA in pregnant women, we investigated two independent groups: 1,687 cases without screening for serum alanine aminotransferase (ALT) (group A) and 333 cases with elevated ALT (> 45 IU/l) (group B), after screening 21,459 pregnant women. In group A, 11 (0.65%) and 21 (1.24%) were anti-HCV-positive by first- and second-generation tests, respectively, while in group B 8 (2.40%) and 19 (5.71%) were positive, respectively. The results revealed by second-generation assays based on either recombinant protein or synthetic peptides were identical, as were the anti-HCV titers in group B. Among 40 second-generation anti-HCV-positive cases, 18 (86%) of 21 in group A and 17 (89%) of the 19 in group B contained serum HCV-RNA by RT PCR. Thus the prevalence of anti-HCV in Taiwanese pregnant women is 1.24% versus 5.71% in those with elevated ALT level. PMID- 8212668 TI - Heparin-associated thrombocytopenia: no association of immune response with HLA. AB - Heparin-associated thrombocytopenia (HAT) is a severe adverse reaction of heparin therapy. Patients with the immunologic type of HAT are at risk of developing arterial and venous thromboembolic complications caused by an antibody which activates platelets in the presence of heparin. Yet, there are no means to identify patients at risk of developing HAT before heparin administration. We investigated the frequency of HLA class-I and class-II antigens in 47 patients with the immunologic type of HAT verified by a positive two-point heparin-induced platelet activation assay. Compared to a control group of 629 healthy individuals HLA antigens B8 and DR3 were less frequent, whereas DR4 and DR53 had a higher frequency. However, none of these antigens proved to be statistically significant. This is another example of an immunologically mediated disease showing no discernible association with the HLA system. PMID- 8212669 TI - Paired plateletpheresis with the CS 3000 plus blood cell separator using the new 30 ml low-volume collection chamber and the A-35 collection chamber. AB - Eight blood donors underwent paired plateletpheresis using the CS 3000 Plus blood cell separator. For each donor, two samples were run: one with the TNX-6 separation and the new 30-ml low-volume collection chamber (LVCC) and one with TNX-6 separation and the A-35 collection chamber. With the LVCC, 4.8 +/- 0.5 x 10(11) thrombocytes could be harvested, whereas 4.4 +/- 1.4 x 10(11) platelets (PLT) were collected with the A-35 chamber. The separation efficiencies were 51.7 +/- 6.6% for the LVCC and 43.8 +/- 10.7% for the A-35 chamber. The leukocyte contamination of the platelet concentrates was not statistically different. PMID- 8212670 TI - Haemolytic anaemia to the alpha-interferon treatment: a proposed mechanism. AB - Auto-immune haemolytic anaemia (AIHA) has been found in a case of alpha interferon treatment. Serum antibody and eluate were positive in the absence of the drug. Although the patient recovered after the treatment was stopped, DAGT remained positive for at least 8 months. The mechanism proposed to explain why this drug induced AIHA is similar to that proposed for alpha-methyl-dopa. Drugs could alter the red cell membrane and impair the immune system. Such changes have been observed with alpha-interferon and were related with increased autoimmunity. PMID- 8212671 TI - Outbreaks of hepatitis A and emergence of new AIDS-associated agents: the need to add terminal 100 degrees C dry-heat sterilization to factor VIII and factor IX concentrates. PMID- 8212672 TI - How to determine the alanine-aminotransferase threshold in blood donors. PMID- 8212673 TI - Use of the gel test to detect mixed red blood cell populations in bone marrow transplantation patients. PMID- 8212674 TI - Neonatal alloimmune thrombocytopenia in Italy. A survey. PMID- 8212675 TI - Letter to the editor with reference to 'Gift or good' by Beal and van Aken. PMID- 8212676 TI - Process-scale purification of immunoglobulin M concentrate. AB - An IgM concentrate was purified from Cohn fraction III. Efficiency of euglobin precipitation was shown to be controlled by pH and ionic strength. Prekallikrein activator activity in the product was insignificant. Overall yield from the octanoic acid supernate and purity of the concentrate were 66 +/- 8 (n = 16) and 50 +/- 5% (n = 16), respectively. Solvent-detergent treatment to inactivate lipid enveloped viruses was demonstrated and implemented into the process. Process studies to control residual virucidal agents and C4a generating activity are presented. PMID- 8212677 TI - Studies in red blood cell preservation. 7. In vivo and in vitro studies with a modified phosphate-ammonium additive solution. AB - Studies were conducted to examine whether an experimental additive solution (EAS 2) containing, in mM: 20 NH4Cl, 30 Na2HPO4, 2 adenine, 110 dextrose, 55 mannitol, pH 7.15, would be useful to extend the storage shelf life of human RBCs. With 6 pairs of split units, ATP concentrations were better maintained for 12 weeks with EAS-2 than with Adsol (1.8 vs. 1.1 mumol/g Hb, respectively, p = 0.002). Autologous 24-hours 51Cr viability values for split units in the same donors were: on 6 paired units at 8 weeks, EAS-2 87.0 +/- 4.5%, Adsol 72.6 +/- 2.3%, p = 0.004; on 11 paired units at 9 weeks, EAS-2 79.5 +/- 7.1%, Adsol 68.2 +/- 10.1%, p = 0.0003. The data suggest that packed RBCs stored for 9 weeks with EAS-2 will be suitable for transfusion following the removal of supernatant with a single washing step. PMID- 8212678 TI - Potassium loss and cellular dehydration of stored erythrocytes following incubation in autologous plasma: role of the KCl cotransport system. AB - We studied the regulation of cell volume and cation content in erythrocytes stored at 4 degrees C under blood bank conditions for various lengths of time and subsequently incubated in autologous plasma at 37 degrees C for 4 or 24 h. Cell swelled during storage at 4 degrees C whereas marked K+ loss and cell shrinkage were observed when erythrocytes were incubated at 37 degrees C in autologous plasma. The cell shrinkage was inhibited only by the K+ Cl- cotransport-specific inhibitor, [(dihydroindenyl)oxy] alkanoic acid, and not by other specific inhibitors of cation transport systems such as ouabain (Na(+)-K+ ATPase pump), bumetanide (Na(+)-K(+)-Cl- cotransport) or carbocyanine (Ca+(+)-activated K+ channel). Acidification and swelling of the erythrocytes are well known to be able to activate the K+ Cl cotransport; such conditions, which were demonstrated to occur during the storage, could lead to activation of the K+ Cl- cotransport in reinfused cells. These data strongly support the evidence that K+ Cl- cotransport plays a role in K+ loss and dehydration of stored erythrocytes, when incubated in autologous plasma. PMID- 8212679 TI - Acute injuries from mountain biking. AB - We questioned members of 2 southern California off-road bicycling organizations about injuries associated with the use of all-terrain bicycles. Cyclists were asked about riding and safety habits, the kind(s) of injury sustained with their most recent accident and whether they sought medical treatment, and the circumstances of the accident. Of 459 mailed surveys, 268 (58.4%) were returned. Respondents (82.8% of whom were male) ranged in age from 14 to 68 years. Of these, 225 (84%) had been injured while riding all-terrain bicycles, 51% in the past year. Although most injuries were characterized as minor, 26% required professional medical care, and 4.4% of those injured were admitted to hospital. Extremity injuries--abrasions, lacerations, contusions--occurred in 201 (90%) cyclists with 27 (12%) sustaining a fracture or dislocation. High levels of helmet use (88%) may explain the low occurrence of head and neck trauma (12%). Frequent riding and riding on paved terrain were associated with increased severity of injury, although most accidents--197 (87.6%)--occurred off paved roads. These results suggest that, compared with regular bicyclists, all-terrain cyclists have more, but not necessarily more severe, injuries. Clinicians and emergency medical personnel should be aware that the increasing popularity of off road cycling may change the frequency and nature of bicycling injuries. PMID- 8212680 TI - Prevention of cesarean section. Does intracervical dinoprostone work? AB - We investigated the effect of preinduction cervical ripening with the intracervical instillation of dinoprostone (prostaglandin E2 gel, 0.5 mg) on the results of labor induced with intravenous oxytocin. We randomly allocated 79 pregnant women to receive either the intracervial application of dinoprostone gel or placebo gel. Compared with control subjects, the group who received dinoprostone had no difference in induction-to-delivery interval or in cesarean section rate. The dinoprostone group had fewer failed inductions, but there was no difference between the two groups in the number who delivered spontaneously within 24 hours. From review of the literature and a meta-analysis, it was likewise revealed that dinoprostone did not favorably affect the cesarean section rate. Contrary to current opinion, intracervical dinoprostone gel does not appreciably lower the cesarean section rate when used at this dose and route before labor is induced. PMID- 8212683 TI - Dysequilibrium in older people. AB - The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in neurology. 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 neurology 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 Neurology of the California Medical Association, and the summaries were prepared under its direction. PMID- 8212682 TI - Atherosclerosis--reversal with therapy. AB - Evidence for atherosclerosis reversal comes from studies in animals wherein atherosclerosis is induced and then allowed to regress, autopsy studies of starved humans, and angiographic studies testing antiatherosclerosis treatment. Animal models and autopsy studies have provided detailed histologic and biochemical descriptions of regression. Cellular and subcellular information exists on what can occur, but because the same lesions are not re-examined, what actually does occur is unknown. Studies of isolated arterial cell systems and intact lesions indicate that atherogenesis involves at least the following: Increased permeability of the endothelium to macromolecules such as low-density lipoprotein; platelet adherence to areas of functional endothelial injury or denudation; the entrance of monocytes or macrophages and lymphocytes into the subintimal space; and the secretion of growth factors by platelets, injured endothelium, and macrophages. These processes can be initiated or enhanced by various vasoactive agents that induce endothelial cell constriction with the opening of endothelial junctions. These processes also can recruit smooth muscle cells from the media to the subintima where they proliferate. Proliferating smooth muscle cells, along with macrophages, can internalize lipids and lipoproteins to form foam cells. Subintimal smooth muscle cells can also synthesize collagen, elastin, glycosaminoglycans, and other connective tissue elements that trap lipoproteins. Peroxidative injury increases the atherogenic potential of both cholesteryl ester-rich (low-density) and triglyceride-rich (very-low-density and intermediate-density) lipoproteins. Steep oxygen gradients within the arterial wall create local conditions for free radical generation, and any increase in residence time of lipoprotein particles can be atherogenic. In summary, there are many areas where treatment may retard or reverse atherogenesis. Angiographic trials that identify and track individual human lesions have shown that reducing known atherogenic risk factors can lessen coronary and femoral atherosclerosis. But they provide no information on events within arterial wall cells or the intracellular matrix. They deal only with lesions that intrude into the vessel lumen and obtain measurements at infrequent intervals. The weight of evidence is that regression is possible, but there is no consensus on the most effective therapy. The challenge for future trials is to select optimal targets for intervention among the known atherogenic processes. PMID- 8212684 TI - Molecular genetics in neurologic diseases. PMID- 8212685 TI - Radiosurgical treatment of brain lesions. PMID- 8212681 TI - Coccidioidomycosis. AB - Coccidioidomycosis is a systemic fungal infection endemic to the southwestern United States and other parts of the western hemisphere. Although producing a wide range of disorders in healthy persons, immunosuppression predisposes to especially severe disease. Thus, a knowledge of the pathogenesis of coccidioidal infections and its relation to the normal immune responses is useful to understand the diversity of problems that Coccidioides immitis may cause. Diagnosis usually requires laboratory studies such as fungal culture or specific serologic testing. Fortunately, many patients do not need to be treated for the infection to resolve. Therapy for the more severe forms of coccidioidal infection was once limited to amphotericin B but now includes azole antifungal agents. These expanded alternatives now require physicians to weigh many factors in determining the best management for specific patients. PMID- 8212686 TI - Ticlopidine hydrochloride and prevention of stroke. PMID- 8212687 TI - Magnetic resonance spectroscopy. PMID- 8212688 TI - Outcomes research--possible effects on clinical practice. PMID- 8212690 TI - Encephalopathy due to severe hyponatremia in an ultramarathon runner. PMID- 8212689 TI - Hyporeninemic hypoaldosteronism complicating primary autonomic insufficiency. PMID- 8212691 TI - Successful enteral refeeding after massive small bowel resection. PMID- 8212692 TI - Early diagnosis of ectopic pregnancy. PMID- 8212693 TI - Academe and government. Firm link or broken reed? PMID- 8212694 TI - Regression of atherosclerosis--an ounce of prevention. PMID- 8212695 TI - Ectopic pregnancy--becoming a nonsurgical disorder. PMID- 8212696 TI - Government and academic health science centers. PMID- 8212698 TI - Educating physicians for international health. PMID- 8212697 TI - A crisis in medical education--one person's concern. PMID- 8212699 TI - False-positive human immunodeficiency virus type I ELISA results in low-risk subjects. PMID- 8212700 TI - The resurgence of saccharin. PMID- 8212701 TI - [Therapy of epilepsy in the elderly]. AB - The incidence of epileptic seizures is high in childhood, but shows regression during adult life until the age of 65 when there is again a marked, age-dependent increase in frequency. The specific problems of anticonvulsive therapy in the elderly are discussed in the light of the sparse literature on this subject. Pathophysiological influences of aging on the pharmacodynamics and pharmacokinetics of antiepileptic drugs have to be taken into account, such as changes in the renal, hepatic and intestinal functions as well as increased neuronal receptor sensitivity, among other factors. The optimal time to start therapy is controversial. In selecting the antiepileptic drug, particular attention must be paid on cognitive dysfunction and impairment of impulse conduction. Moreover, age-dependent side effects, as well as possible additive effects due to interaction with other medication have to be taken into consideration. In view of the high rate of relapses great caution has to be taken to withdraw the antiepileptic drugs in completion of the therapeutic regimen. PMID- 8212702 TI - [Tarsal tunnel syndrome. Diagnosis and differential diagnosis]. AB - The tarsal tunnel syndrome represents an entrapment neuropathy of the tibial nerve behind the internal malleolus under the retinaculum of the flexor muscles of the foot. In more than 3 out of 4 cases, it is a late consequence of twisting or fracture of the ankle. Local pain is increased by walking. In addition to local pain on pressure behind the internal malleolus, at a later stage paresis of the small foot muscles becomes evident with impaired abduction of the toes, decreased sensation and abnormally dry, smooth skin over the sole of the foot. The impairment of tibial nerve function can also be shown electrophysiologically. Surgical treatment is recommended for advanced cases. PMID- 8212703 TI - [Pain syndromes of the tibial nerve at the leg-foot transition]. AB - The prognosis of surgical treatment of the tarsal tunnel syndrome (TTS) with regard to total pain relief is worse than following surgery of the carpal tunnel syndrome. In TTS, additional static factors play a role. The indication for surgery, therefore, is made with utmost reluctance. The surgical strategy is described extensively. In the majority of patients a considerable improvement of symptoms can be achieved. There are, however, individual patients in whom surgical intervention is followed by increased pain. Three such patients are reported. This pain syndrome is caused and increased by recurrent fibrosis of the nerve bed, eventually including the integument and inducing entrapment neuropathy by the contracted dermal covering. Surgical resolution of this problem is transplantation of soft tissues to surround the nerve and skin grafting to augment the covering dermal layer. PMID- 8212704 TI - [Pathology of the central nervous system in AIDS. An overview of 184 patients]. AB - Based on a consecutive autopsy series of 184 patients with AIDS, a critical review of the pathology of the central nervous system (CNS) is given. The lesions can be divided into three groups: 1. opportunistic/non-opportunistic infections, 2. changes due to the human immunodeficiency virus (HIV), and 3. neoplasms. The frequency and morphology of CNS lesions in our cohort are compared with those in other series. Marked lesions of the CNS were found in 111 patients (60%), while mild/nonspecific changes were seen in 52 cases (28%). Toxoplasmosis (23%) was the most frequent CNS infection, followed by cytomegalovirus (17%), and papovirus (5%). HIV giant cell encephalitis, HIV leukoencephalopathy, vacuolar myelopathy and leukoencephalopathy were observed in 11%. Primary CNS lymphomas were present in 6%, while secondary involvement of the CNS in systemic lymphomas was seen in only two cases (1%). Lesions due to CNS infections in patients with AIDS often show atypical patterns, and frequently, there are multiple infections with simultaneous involvement of the CNS by lesions of different etiology. The present study confirms the frequent involvement of the CNS in AIDS, although there are differences in the incidence and pattern of lesions related to geographic and/or demographic factors. PMID- 8212705 TI - [Apomorphine test in Parkinson disease--dose and corresponding parameters]. AB - The apomorphine test is a well known indicator of therapeutic responsiveness to dopaminergic substances and a reliable instrument for the differential diagnosis of idiopathic Parkinson's disease. The relationship between apomorphine dosage and the following parameters, namely age, duration of disease, body height, body surface, skinfold thickness of the abdominal wall and the upper arm as a measure of subcutaneous fatty tissue, and amount of administered L-dopa was studied in 45 patients with Parkinson's disease in whom the apomorphine test was positive. In addition we investigated whether different doses of apomorphine resulted in significant differences of the parameters studied. The determined parameters correlated with the given dose of apomorphine (p < 0.05) and thus, represent a potential indicator for optimal L-dopa dose determination and intermittent or continuous apomorphine administration. PMID- 8212707 TI - [Low dose acetylsalicylic acid in secondary prevention of stroke]. AB - Acetylsalicylic acid (ASA) as secondary prophylaxis after ischaemic cerebrovascular events is well established and its efficacy unquestioned since over 15 years. According to the results of two European studies a dose of 100 mg per day is sufficient to reduce the incidence of further stroke, myocardial infarction, and death due to cardiovascular causes. This satisfactory response to low-dose ASA applies to patients with transient ischaemic attacks, reversible ischaemic events, and minor strokes. In cases with severe cardiac disease, however, a high dosage of ASA or anticoagulation therapy may be necessary to prevent further vascular events. PMID- 8212706 TI - [Serevent. Salmeterolxinafoate]. PMID- 8212709 TI - [Prospective study of determining the value of D-dimer in diagnosing pulmonary embolism]. AB - Pulmonary embolism (PE) is still misdiagnosed in a high proportion of cases. 107 patients admitted for suspected pulmonary embolism were studied prospectively to shed light on the value of ELISA-D-dimer and Latex-D-dimer. Pulmonary embolism was ruled out by negative perfusion scans in 66 patients (61.7%) and by angiography in 24 patients. 58% of the scans suggesting a high probability of PE were confirmed by angiography, but only 18% of the scans suggesting a low or intermediate probability of PE. Sensitivity and specificity were 88% and 79%, respectively for the D-dimer ELISA, versus 94% and 90% for the Latex agglutination test. The Latex test increased the positive predictive value of lung scanning suggesting low to intermediate probability of PE (group B) from 18% to 75% and that of lung scanning suggesting high probability of PE (group C) from 58% to 93%. The positive predictive value was improved by ELISA-D-dimer in both groups to 75%. In order to augment the diagnostic efficacy in clinical practice the determination of Latex-D-dimer simultaneously with lung scanning is recommended. PMID- 8212708 TI - Evaluation of the role of coronary heart disease and left ventricular contractile function in systolic mitral valve displacement. AB - It has been suggested that systolic bulging of the mitral valve caused by ischaemia induced left ventricular dysfunction may ultimately lead to mitral valve prolapse, making coronary heart disease the most important cause of secondary mitral valve prolapse. The influence of coronary heart disease on systolic displacement of the mitral valve was assessed in 90 consecutive patients with chest pain who were evaluated with coronary angiography and ventriculography of the left ventricle. 22 patients had coronary heart disease affecting one vessel (one vessel disease, OVD), 35 patients had coronary heart disease affecting more than one vessel (multiple vessel disease, MVD), and 33 patients had normal coronary arteries. The prevalence of mitral valve bulging was also determined in 16 patients with dilatative cardiomyopathy (CMP). Prevalence of mitral valve bulging in patients with OVD was not significantly different from normal patients. Patients with MVD and CMP had a lower prevalence of mitral valve bulging than normal patients and patients with OVD (p < 0.001). When all patients were grouped according to their ejection fraction, regardless of their underlying disease, there was a positive correlation between prevalence of mitral valve bulging and ejection fraction (r = 0.98, p < 0.001). Patients with an ejection fraction of below 50% did not have mitral valve bulging. We conclude that coronary heart disease is not a cause of mitral valve bulging and, furthermore, that systolic mitral valve bulging may serve as indicator of good left ventricular contractile function. PMID- 8212710 TI - Selenium status of elderly Austrians suffering from circulation disorders. AB - Whole blood selenium status of 299 persons, 144 women and 155 men, with a mean age of 62 +/- 10 years, has been determined. The individuals came from all Austrian provinces to Bad Hall to improve their heart and circulation disorders. The mean selenium content was 95 micrograms/l. We found no correlations between selenium levels and GSH-peroxidase, cholesterol, HDL-cholesterol and triglycerides. PMID- 8212711 TI - [Digitoxin-induced thrombocytopenia]. AB - A 82-year-old woman was admitted to hospital because of heart failure, vomiting, and pain in the right upper abdomen. During the past three months she had received treatment with 0.07 mg digitoxin twice daily. The ECG showed sinus bradycardia with intermittent complete sinoatrial block. On the basis of the history, clinical presentation and ECG findings digitalis intoxication was suspected. Digitoxin level was 65.23 ng/ml--far beyond the therapeutic range. Laboratory examinations revealed a marked thrombocytopenia (25,000/microliters). The patient was placed on cholestyramine (4g three times daily) to accelerate intestinal excretion of digitoxin. As there were no life-threatening complications there was no indication for treatment with digitalis-specific antibodies. On the 6th day after discontinuation of digitoxin treatment the platelet count showed a marked rise and returned to normal values as from the 12th day. PMID- 8212712 TI - [Molecular biology studies of complement C4 gene in patients with systemic lupus erythematosus]. PMID- 8212713 TI - [Atrophy of mandibular bones in implanted prostheses. Evaluation of conventional assessment criteria]. PMID- 8212714 TI - [Bioprosthesis degeneration in the aortic and mitral valve position. Results and problems from the cardiosurgical viewpoint]. AB - 38 patients (20 men, 18 women) underwent reoperation between July 1989 to September 1992 because of degeneration of bioprosthetic valves implanted in aortic or/and mitral position. Retrospective analysis revealed a mean implantation time of 116.5 +/- 31.5 months for the bioprostheses (median 116). At reoperation 63.2% of them had a single valve replacement, 36.8% a more complex cardiac procedure (double or triple valve replacement, valve replacement and coronary bypass grafting). 50% (n = 9) of the reoperation cohort were symptomatic (NYHA III), 16 (42.1%) were serious symptomatic (NYHA IV). All deaths were NYHA IV preoperatively. Early mortality was 18.4% (n = 7). Mean age at the time of first operation was 51 +/- 10.7, mean age at reoperation was 60.5 +/- 10.6. There was a significantly longer aortic clamp time (AKT, p = 0.0005) and bypass time (BPT, p = 0.0000) compared to first operation, also a significantly longer BPT of the deads confronted with the survivors (p = 0.0075). Bioprosthetic valves in mitral position were significantly longer implanted (p = 0.0416) than in aortic position. But there was no difference in implantation time of commercially available Carpentier-Edwards- or Ionescu-Shiley grafts. At reoperation we changed more than 95% of the degenerated valves to mechanical devices--corresponding to international tendencies. We discuss the early tissue degeneration of bioprosthetic valves and their increasing problem during reoperation. PMID- 8212715 TI - [Antihypertensive effectiveness of enalapril and hydrochlorothiazide as a combination drug]. AB - 1062 patients with moderate to severe hypertension were enrolled in an open-label multicenter trial investigating the antihypertensive efficacy and safety of the preconstituted formulation enalapril (20 mg) and hydrochlorothiazide (12.5 mg) over a treatment period of 12 weeks. According to the inclusion criteria of the study protocol 489 patients had to be excluded from statistical evaluation of efficacy. Results were calculated from 573 patients (339 females, 234 males, mean age 59.1 +/- 12.3 years) of whom 89% (n = 510) received the standard dosage of 1 tablet daily. They revealed a significant reduction (p < 0.001) of both diastolic and systolic blood pressure (BP) from a mean of 108.2 +/- 7.8 mm Hg (182.2 +/- 17.6 mm Hg) before treatment to a mean of 88.4 +/- 6.7 mm Hg (152.6 +/- 10.8 respectively) after 12 weeks of treatment. 81% responded to therapy defined as a lowering of diastolic BP < 90 mm Hg. Heart frequency dropped significantly (from a mean of 77.8 +/- 10.6 to a mean of 71.7 +/- 8.0, p < 0.01), too. Adverse effects leading to discontinuation were seen in 2.8% (n = 30) of all participating patients. Cough and gastrointestinal discomfort were the most frequent side effects. None of the safety parameters i.e. serum potassium and creatinine changed during the period of investigation. In conclusion, the preconstituted formulation enalapril (20 mg) and hydrochlorothiazide (12.5 mg) was shown to be an effective and well tolerated treatment not only for patients with newly diagnosed moderate to severe hypertension, but also for nonresponders to previous antihypertensive therapy. PMID- 8212716 TI - [Congenital fistulas of the coronary arteries. A review with case presentations]. AB - Coronary artery fistulas are rare atypical communications between a coronary artery and a cardiac chamber or other great vascular structure and usually congenital in origin. Many are detected accidentally by the use of coronary angiography. These fistulas often have minor hemodynamical significance and the course is primarily from the proximal left coronary artery to the pulmonary artery. Though symptoms are rare they should be observed carefully in aspect of possible complications. In contrast sometimes coronary artery fistulas are found when searching for the cause of cardiac murmurs or clinical symptoms. Great amounts of shunted blood can result in cardiac volume overload and myocardial ischemia may occur by coronary steal. Surgical closure of these fistulas is the treatment of choice. In our laboratory we found in a series of 3,000 coronary angiographies a 53 year old man with an abnormal communication from the right coronary artery to the right atrium and a 68 year old woman with a fistula from the proximal left anterior descending artery to the pulmonary artery. PMID- 8212717 TI - [What coronary findings predispose to premature termination of a strong positive dipyridamole test?]. AB - Besides the exercise-ECG the dipyridamole-test is used in the noninvasive diagnosis of coronary artery disease (CAD). In many cases the test must be terminated due to angina or ST-segment depression before reaching the regular end point of the investigation. The test then is graded as highly positive. It was the aim of this study to answer the question what changes in the coronary angiogram one has to expect in patients with a highly positive dipyridamole-test. In 45 females and 173 males the dipyridamole-test was carried out giving 0.75 mg dipyridamole/kg bodyweight intravenously over a period of 10 min. In case of angina pectoris and/or ST-segment depression > 0.2 mV occurring within 12 min after beginning of injection the test was graded positive. The test was defined highly positive in the case of early termination during the injection period because of angina or ST-segment depression. All patients had undergone a coronary angiography. 70 out of 218 dipyridamole-tests had to be terminated before the regular end of the test. There was no correlation between the time of termination of the dipyridamole-test and the grade of CAD. The group of patients in which the test had to be terminated early because of angina and ST-segment depression more often had coronary stenoses > 75% in at least one major coronary artery (94.5%) compared with those patients in which only angina led to the termination of the test (69.6%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212718 TI - [Research hindrance in medicine. (A completely imaginary satire)]. PMID- 8212719 TI - [Osteoporosis. Attitude and opinion of Austrian physicians]. AB - 251 participants of a representative sample of Austrian physicians (general practitoners, gynecologists, internists) stated their attitudes towards osteoporosis risk factors and methods of prevention. About half of the doctors believe that osteoporosis has less influence on public health than coronary heart disease, stroke or diabetes. Concerning osteoporosis they estimate prevention as most important. For the doctors the most effective preventive strategies, for pre as well as for postmenopausal women, are physical activity, high calcium intake, and postmenopausal estrogen replacement therapy. Some of the risk factors are very close to the individual lifestyle (e.g. physical activity, nutrition and smoking), 83% of the physicians think that lack of exercise has a great influence on osteoporosis risk, 64% think the same about low calcium intake, 95% about lack of estrogen and 80% about positive family history. Within the physicians as well as the general population osteoporosis awareness is most important concerning growing life expectancy and demographic aspects. Due to this fact it is essential that more than two thirds of the doctors estimate preventive measures as successful. PMID- 8212720 TI - [Gender-specific differences of risk factors of atherosclerosis. A study of 3,850 Vienna employees]. AB - Atherosclerosis is the most frequent cause of death in Austria as well as in the other western industrialized countries. Sex specific differences in the various age groups concerning relative myocardial infarction-mortality stimulated us to investigate the risk factors for atherosclerosis in 3850 employees. An extensive lipid status, liver and kidney function parameters were determined, the blood pressure was measured, and a cardiovascular centered case history was examined. The mean cholesterol level and the LDL-cholesterol level in males were significantly higher than in females (cholesterol: males 223.8 +/- 56.8 mg/dl, females 208.2 +/- 43.3 mg/dl, LDL-cholesterol: male 151.9 +/- 55.1 mg/dl, female 132.2 +/- 40.1 mg/dl, p < 0.001). The mean HDL-cholesterol level in males were significantly lower than in females (males: 45.0 +/- 11.6 mg/dl, females 56.2 +/- 13.3 mg/dl, p < 0.001). No significant difference concerning smoking-behaviour could be determined between female and male participants in this cohort (33.0% of the males resp. 33.6% of the females stated that they smoked cigarettes). Hypercholesterolaemia and cigarette-smoking are the main risk factors for both sexes, however the situation of women-except for the 6th decade-is much better than that of men. Remarkable is the increasing number of female-smokers, especially at younger age. PMID- 8212721 TI - [Eating behavior of patients with metabolic diseases and metabolically healthy probands in Austria. Results of a questionnaire survey at the Graz Autumn Fair 1991]. AB - Malnutrition as the cause of developing atherosclerosis is undoubtedly of major importance. For that reason, proper nutrition and eating habits among the population is of specific significance in preventive medicine. In order to establish a more pronounced food consciousness among the population of Styria, a questionnaire was issued to 1.354 persons attending the Graz Autumn Fair in 1991. The results showed above all that approximately 40% of the subjects investigated presented a disease due to malnutrition and metabolic disorder, mainly hyperlipidemia. The choice of various foods varied according to male and female tastes; roasted pork was more often a men's favourite dish (p < 0.001) while women had a prediction for vegetarian food (p < 0.001). There was, however, no difference in the choice of eating habits in persons with or without metabolic disorders. Thus, women in general do pursue a healthier consciousness was not so pronounced in man. Yet, it could not be established by means of the questionnaire that subjects with metabolic disorders showed different eating habits with respect to their disease. PMID- 8212722 TI - Advocacy groups provide vital support for brain disease patients. PMID- 8212723 TI - Delayed recovery from post-thyroidectomy hypoparathyroidism: a case report. AB - Thirteen hours after a subtotal thyroidectomy was performed for hyperthyroidism, a patient developed carpopedal spasms, parathesias and hypocalcemia to 6.9 mg/dL. After initial stabilization with intravenous calcium administration, oral calcium carbonate and calcitriol were required. Ten months postoperatively serum calcium levels rose and supplementation was gradually discontinued. The serum parathyroid hormone (PTH) level was 1.0 pg/mL on the second postoperative day and levels were undetectable despite sensitive testing 3 months later (normal 10-65 pg/mL). Two years after surgery, the PTH level has increased to 36 pg/mL, but remains relatively low considering the patient's continued mild hypocalcemia. To our knowledge, there has been no previously reported case of long-term post thyroidectomy hypocalcemia documenting undetectable parathyroid function and subsequent spontaneous improvement. This case suggests that delayed recovery of parathyroid function and discontinuation of vitamin D and calcium supplementation may be possible in some post-thyroidectomy patients with hypocalcemia due to severe hypoparathyroidism. PMID- 8212725 TI - Statewide physician health program. PMID- 8212724 TI - Adult children of alcoholics: exploring positive life outcomes. PMID- 8212726 TI - Physicians Insurance Company of Wisconsin: state of the corporation. PMID- 8212727 TI - The fate and effects of transiting, nonpathogenic microorganisms in the human intestine. PMID- 8212728 TI - Interactions between the intestinal flora and xenobiotic metabolizing enzymes and their health consequences. PMID- 8212729 TI - Immune responses to dietary protein antigens. PMID- 8212730 TI - Human diseases due to food-borne bacterial toxins and toxins produced in the digestive tract. PMID- 8212731 TI - Physiological and pathophysiological effects of carbohydrate fermentation. PMID- 8212732 TI - Relationship between pharmacokinetics and pharmacodynamics of tinzaparin (logiparin), a low molecular weight heparin, in dogs. AB - 1. Pharmacodynamic models relating the plasma concentrations (C) of radioactive heparin material to anticoagulant effect (E) have been investigated after single i.v. and s.c. doses of 3H-tinzaparin (1 and 4 mg/kg), a radiolabelled low molecular weight heparin, to six dogs. 2. A counterclockwise hysteresis, characterizing the C versus E relationship, was observed in all animals after s.c., but not i.v., doses indicating a possible delay (lag-time) in the systemic availability of pharmacologically-active heparin material following extravascular administration. A constant (Ke) was introduced into the model to account for this hysteresis. 3. At high plasma concentrations of radioactivity (> 10 micrograms/ml), E was related to C by a sum of two sigmoid Emax models, whereas, at lower concentrations, this reduced to the well-known sigmoid Emax model. It was proposed that tinzaparin activates two 'receptors' having different affinities for the drug. The values of EC50 associated with the activation of a single 'receptor' and of a proposed additional 'receptor' were 3 and 13 micrograms/ml of heparin material, respectively. 4. Heparin material was predominantly eliminated by renal excretion and underwent widespread tissue distribution. After s.c. administration, input of heparin material into systemic plasma was complete within 12 h post-dose, and the absorption process was characterized by a bi-exponential function. 5. We conclude that sigmoid Emax models adequately describe the C versus E relationship after s.c. and i.v. doses of 3H-tinzaparin in dogs and that the interindividual variation of the pharmacodynamic parameters derived from this model was relatively small. PMID- 8212733 TI - Pharmacokinetics of a new thienodiazepine platelet activating factor receptor antagonist (E6123) in laboratory animals. Is there a metabolic polymorphism in the rhesus monkey? AB - 1. The pharmacokinetics of E6123, a platelet activating factor receptor antagonist, were studied after i.v. and oral administration to rat, guinea-pig, dog and rhesus monkey. Plasma concentrations of E6123 were determined by h.p.l.c. with UV detection. 2. After i.v. dosing (1 mg/kg), the plasma concentration-time curves fitted a two-compartment model. The half-lives for the terminal phases (t1/2) in rat, dog, and guinea-pig showed very little inter-individual variation, but t1/2 in the monkey (n = 4) varied more than four-fold. The distribution parameters were very similar in rat, dog and monkey (Vc and Vss approx. 1.2 and 1.5 l/kg, respectively) but slightly higher values were found in the guinea-pig, which also showed the lowest plasma protein binding. 3. After oral dosing (1 mg/kg), the maximum plasma concentrations were obtained within 0.3-3.0 h in all species. The half-life for each individual animal was almost the same as that after i.v. dosing. The mean bioavailabilities of E6123 in rat, guinea-pig and dog were about 65, 95 and 81%, respectively, but the values for monkey were again highly variable (range 32-99%). 4. The high variability in the monkey was confirmed by i.v. administration to a further 10 animals. The mean half-lives for the terminal phase in extensive metabolizers (EMs) (n = 4) and poor metabolizers (PMs) (n = 10) were approx. 1 and 4 h, respectively. 5. The rank order for total body clearance of E6123 was: rat > monkey (EMs) > dog > guinea-pig > monkey (PMs). PMID- 8212734 TI - Metabolic polymorphism of E6123 in rhesus monkey. AB - 1. The metabolic polymorphism of a new thienodiazepine platelet activating factor receptor antagonist (E6123) in rhesus monkey was studied in vivo and in vitro. 2. After i.v. dosing of 14C-E6123, the levels of radioactivity in blood, plasma and red blood cells were higher in poor metabolizers (PMs) with AUC(0-24 h) values which were about 1.3-1.5 times higher than those in extensive metabolizers (EMs). 3. After i.v. dosing of 14C-E6123, radioactivity was excreted rapidly by both EMs and PMs. However, EMs excreted the radioactivity mainly in urine whereas, for PMs, radioactivity was excreted fairly equally in urine and faeces. 4. In vivo and in vitro studies demonstrated that the metabolic polymorphism of E6123 in rhesus monkey is caused by a difference in the hydrolysis of an amide side chain. 5. Our results suggested that there are two types of the enzymes which metabolize E6123 by this route in EMs, but only one type in PMs. 6. The low affinity enzyme in EMs might be the same as the enzyme in PMs, indicating that the metabolic polymorphism of E6123 in rhesus monkey could depend on the existence of a high affinity enzyme. PMID- 8212735 TI - Metabolism of N-[4-chloro-2-fluoro-5-[(1-methyl-2- propynl)oxy]phenyl]-3,4,5,6 tetrahydrophthalimide (S-23121) in the rat: I. Identification of a new, sulphonic acid type of conjugate. AB - 1. Several metabolites of 14C-labelled N-[4-chloro-2-fluoro-5-[(1-methyl- 2 propynyl)oxy]phenyl]-3,4,5,6-tetra-hydrophthalimide (S-23121) were identified. 2. The major urinary metabolites were found to be 4-chloro-2-fluoro-5 hydroxyaniline, its sulphate and glucuronide by t.l.c. cochromatography with authentic standards. 3. The major faecal metabolites in addition to the parent compound were six sulphonic acid conjugates having a sulphonic acid group incorporated into the double bond of the 3,4,5,6-tetrahydrophthalimide moiety. These sulphonic acid conjugates have never been reported previously for this type of compound. 4. To confirm the mechanism of biosynthesis of the sulphonic acid conjugates, sodium sulphate, cysteine and glutathione labelled with 35S were administered to the male rat together with unlabelled S-23121. The same faecal metabolites as those detected in faeces of the rat dosed with 14C-labelled S 23121 were similarly found after dosing with any of the 35S-labelled chemicals. Their biosynthesis was most pronounced with 35S-labelled sodium sulphate, implying that the sulphonic acid is incorporated into the double bond after reduction of sulphate to sulphite. PMID- 8212736 TI - Identification of four biliary metabolites of the diterpene sclareol in the laboratory rat. AB - 1. Ag.l.c. method was developed to determine sclareol (1) and its microbial metabolites: 3-keto-sclareol (2), 2 alpha-hydroxysclareol (3), 3 alpha hydroxysclareol (4), 3 beta-hydroxysclareol (5), 18-hydroxysclareol (6), and 2 alpha, 18-dihydroxysclareol (7) in both microbial cultures and biological fluids of the laboratory rat. 2. Metabolism of the diterpene (1) was studied in the laboratory rat. This in vivo study was facilitated by the availability of microbial metabolites of sclareol as reference standards, and the g.l.c. assay for sclareol and its metabolites in biological fluids. 3. Following i.v. treatment (100 mg/kg), the disappearance of (1) from rat plasma was rapid and biphasic. No microbial metabolites of sclareol were detectable in plasma. 4. Sclareol (1) and its microbial metabolites were not detected in rat urine following either i.v. or oral treatments; unchanged (1) was excreted in rat faeces to the extent of 9% of an oral dose in 48 h. 5. Following i.v. treatment, 0.02% dose was recovered in bile as unchanged (1). Four biliary metabolites of (1) (0.4% dose) were identified as (2), and (4)-(6) based on g.l.c.-mass spectrometry and comparisons with reference standards. All four biliary metabolites of (1) in rat have been identified as microbial metabolites of (1). PMID- 8212737 TI - Generalized cytochrome P450-mediated oxidation and oxygenation reactions in aromatic substrates with activated N-H, O-H, C-H, or S-H substituents. AB - 1. The general mechanism of metabolic oxidation of substrates by cytochromes P450 (P450s) appears to consist of sequential one-electron oxidation steps rather than of a single concerted transfer of activated oxygen species from P450 to substrates. 2. In case of the acetanilides paracetamol (PAR), phenacetin (PHEN), and 4-chloro-acetanilide (4-CLAA), the first one-electron oxidation step consists of a hydrogen abstraction from the acetylamino nitrogen and/or from the other side-chain substituent on the aromatic ring. The substrate radicals thus formed delocalize their spin and the respective reactive centres of the substrate radical recombine with a P450 iron-bound hydroxyl radical to either yield oxygenated metabolites, or undergo a second hydrogen abstraction forming dehydrogenated products. By this mechanism, the formation of all known oxidative metabolites of PAR, PHEN, and 4-ClAA can be explained. Furthermore, this mechanism is consistent with all available experimental data on [18O]PAR/PHEN, [2H]PAR, and [14C]PHEN. 3. The oxidative metabolic reactions proposed for the acetanilides PAR, PHEN, and 4-ClAA are used to generalize P450-mediated oxidations of these and other acetanilides, such as analogues of PAR and 2-N acetyl-aminofluorene. 4. A further generalization of the hydrogen abstraction, spin delocalization, radical recombination concept is derived for other aromatic substrates with abstractable hydrogen atoms, notably those with activated N-H, O H, C-H, or S-H bonds directly attached to the aromatic nucleus. PMID- 8212738 TI - Urinary metabolites of pinacidil. II. Species difference in the metabolism of pinacidil. AB - 1. Pinacidil was given orally to rabbit (10 mg/kg), dog (10 mg/kg), monkey (10 mg/kg) and mouse (150 mg/kg), the urinary metabolites were separated by h.p.l.c. and their structures determined by mass spectrometry. 2. Three new metabolites, namely, omega-hydroxy-pinacidil-O-glucuronide (M-8), pinacidil-pyridine-N-oxide-O glucuronide (M-9) and pinacidil-pyridine-N-glucuronide (M-10) were isolated from rabbit urine, and one new metabolite, namely, pinacidil-pyridine-phenolic glucuronide (M-11) was isolated from mouse urine. 3. M-9 is a unique glucuronide because the glucuronic acid is linked to the oxygen of pyridine-N-oxide. 4. In man, similar to rat, dog and mouse, pinacidil-pyridine-N-oxide (M-1) was the main urinary metabolite, with pyridine-N-oxidation being the major metabolic pathway. On the other hand, M-8 and M-9 were the most abundant metabolites in monkey and rabbit urine, respectively. Therefore, rat, dog and mouse have similar metabolism of pinacidil to man, but monkey and rabbit are significantly different in their metabolism of the drug. PMID- 8212739 TI - Human liver microsomal thiol methyltransferase: inhibition by arylalkylamines. AB - 1. Thiol methyltransferase (TMT) is a microsomal enzyme catalyzing the S methylation of aliphatic sulphydryl drugs and xenobiotics. Studies of the functional significance of S-methylation catalysed by TMT have been hampered by lack of a potent, relatively specific, non-toxic inhibitor of the enzyme. 2. Human hepatic microsomal TMT was inhibited by the arylalkylamine 2,3-dichloro alpha-methylbenzylamine (DCMB), and by a series of arylalkylamines, as well as the arylamine, aniline. 3. Inhibition kinetic studies with DCMB, benzylamine, aniline, phenylethylamine and phenylethanolamine, five compounds with a wide range of IC50 values, showed 'mixed' inhibition of TMT with respect to the methyl acceptor substrate, 2-mercaptoethanol. Kis and Kii values were, respectively, 1.1 and 0.29 microM for DCMB, 160 microM each for benzylamine, 680 and 370 microM for aniline, 1640 and 1380 microM for phenylethylamine, and 2300 and 1400 microM for phenylethanolamine. Inhibition was at least partially reversible. 4. H.p.l.c. analyses were carried out with the products of enzyme reactions performed in the presence of aniline, benzylamine, and phenylethylamine to ascertain whether these compounds inhibited TMT by acting as methyl acceptors. Results showed that they did not act as methyl acceptor substrates. PMID- 8212740 TI - S-methyltransferases in human intestine: differential distribution of the microsomal thiol methyltransferase and cytosolic thiopurine methyltransferase along the human bowel. AB - 1. The activities of the microsomal thiol methyltransferase and the cytosolic thiopurine methyltransferase were measured with 2-mercaptoethanol and 6 mercaptopurine as substrates in human ileum, ascending colon, transverse colon, descending colon and liver. 2. Thiol methyltransferase activity (pmol/min per mg) (mean +/- SD) was 495 +/- 280 (ileum), 786 +/- 454 (ascending colon), 1791 +/- 233 (transverse colon), 964 +/- 484 (descending colon) and 4800 +/- 1194 (liver). 3. Thiopurine methyltransferase (pmol/min per mg) (mean +/- SD) was 53.5 +/- 15.4 (ileum), 34.6 +/- 11.4 (ascending colon), 64.3 +/- 12.1 (transverse colon), 57.0 +/- 10.1 (descending colon) and 106 +/- 20.4 (liver). 4. Transferase in intestinal mucosa followed non-Michaelis-Menten kinetics, and two phases representing high and low affinity forms, for the acceptor methyl substrates were observed. 5. Comparison of intestinal with hepatic activities showed that thiopurine methyltransferase is better expressed than thiol methyltransferase in the human intestine, at least with the substrates studied. PMID- 8212741 TI - Effect of phenobarbital and other model inducers on cytochrome P450 isoenzymes in primary culture of dog hepatocytes. AB - 1. The effects of phenobarbital (PB), beta-naphthoflavone (beta-NF), omeprazole (Omep) and rifampicin (Rif) on drug-metabolizing activities in dog hepatocytes, cultured with William's medium E, were examined. 2. The drug metabolizing activities of the hepatocytes decreased during culture; 7-ethoxycoumarin O deethylase (ECOD) activity was nearly 70% of initial value at 72 h, but 7 methoxycoumarin O-demethylase (MCOD), 7-propoxycoumarin O-depropylase (PCOD), progesterone 6 beta-hydroxylase (6 beta-OH-P), progesterone 16 alpha-hydroxylase (16 alpha-OH-P), progesterone 21-hydroxylase (21-OH-P), 7-ethoxyresorufin O deethylase (EROD) activities and total cytochrome P450 content were approx. 50%. 3. When the hepatocytes were cultured with PB, the enzyme activities increased time- and dose-dependently. MCOD, ECOD and PCOD activities increased 5-8 fold with 2 mM PB in 96 h. Similar results were obtained for 6 beta-OH-P, 16 alpha-OH P and 21-OH-P activities, and total cytochrome P450. The effect of PB was abolished when 2.5 microM cycloheximide or 0.1 microM actinomycin D was included in the culture. 4. Treatment of hepatocytes with 40 microM beta-NF for 72 h resulted in 25-fold elevation of EROD activity. beta-NF enhanced PCOD activity approx. six-fold, while ECOD increased only slightly, and 7-MCOD negligibly. 5. Omep (100 microM) increased EROD activity nearly 10-fold, and 25 microM Rif increased 6 beta-OH-P activity approx. 8-fold, but ECOD only slightly. 6. Western blot analysis of microsomes from cultured dog hepatocytes with anti-rat CYP 2B1 antibodies indicated that PB increased an immunochemically-reactive protein. The protein showed the same mobility as the major dog P450 isozyme (cytochrome P450 PBD-2 or CYP 2B11) purified from liver microsomes of PB-treated male beagle dog. In a similar manner, induction of cytochrome P450 PBD-1 (CYP 3A12) by PB was confirmed. PMID- 8212742 TI - Metabolism of 1-(4-hydroxy-3-methoxyphenyl)-2-propanone, a smoke flavour ketone, in rat. AB - 1. Metabolites of 1-(4-hydroxy-3-methoxyphenyl)-2-propanone (HMP-one), a smoke flavour compound, were isolated from rat urine using hydrolysis, ether extraction, t.l.c. and g.l.c. 2. Three metabolites were identified by mass spectrometry and independent synthesis, namely: 1-(3, 4-dihydroxyphenyl)-2 propanone (Met I), 1-(3, 4-dihydroxyphenyl)-2-propanol (Met II), and 1-(4-hydroxy 3-methoxyphenyl)-2-propanol (Met III). 3. A g.l.c. method for the quantitative determination of the parent compound and metabolites in urine was devised. Unchanged HMP-one accounted for about 74% dose, with Met I 11%, Met II 5%, and Met III 9%. All compounds were excreted both as sulphate and glucuronide conjugates. PMID- 8212743 TI - Regulation of CYP1A induction in hepatoma 27 depending on the site of transplantation. AB - 1. Rat hepatoma 27 after intrahepatic transplantation shows a low but detectable level of cytochrome P450 and P450-dependent activities. The same hepatoma transplanted intramuscularly does not show a detectable amount of cytochrome P450 and P450-dependent activities. 2. Different types of cytochrome P4501A inducers were able to induce 1A isoforms in the intrahepatic hepatoma 27 transplants but not in the intramuscular transplants. 3. Immunohistochemical analysis demonstrates that not all cells in hepatoma 27 transplanted into the liver could be induced with 1A-inducer. The cells of the adenomatous structures of hepatoma 27 are not reactive with 1A antibodies. PMID- 8212744 TI - Metabolism of phentermine and its derivatives in the male Wistar rat. AB - 1. Urinary metabolites of the male Wistar rat dosed i.p. and orally with phentermine (Ph), N-hydroxyphentermine (N-hydroxy-Ph) and p-hydroxyphentermine (p hydroxy-Ph) were examined by g.l.c. and g.l.c.-mass spectroscopy. 2. N-hydroxy-Ph which accounted for about 3% dose was identified in the urine of rat dosed i.p. and orally with Ph. The major urinary metabolite of Ph dosed i.p. and orally was a p-hydroxy-Ph conjugate (51% dose). 3. The major urinary metabolite of N-hydroxy Ph dosed i.p. and orally was a p-hydroxy-Ph conjugate (40% dose). A N-hydroxy-Ph conjugate (12% dose) was identified following i.p. administration of N-hydroxy Ph, but was not detected following oral administration. Small amounts of Ph (< 10% dose) and p-hydroxy-Ph (3% dose) were also identified after i.p. and oral administration of N-hydroxy-Ph. 4. The only urinary metabolite of p-hydroxy-Ph after either i.p. or oral dosing was a p-hydroxy-Ph conjugate (65% dose). 5. These results indicate that N-hydroxy-Ph is a urinary metabolite of Ph in rat; p hydroxy-Ph is produced by the hydroxylation of Ph itself and partly by the hydroxylation of Ph formed from N-hydroxy-Ph; the p-hydroxy-Ph conjugate is the major and final metabolite of Ph dosed i.p. and orally. PMID- 8212745 TI - [Differential therapy of ventricular arrhythmias]. PMID- 8212746 TI - [Diagnosis and clinical aspects of supraventricular tachycardia]. AB - Supraventricular tachycardias are the most frequently occurring manifestations of arrhythmia. They make very high demands on the physician in respect of differential diagnosis and clinical assessment. Atrial tachycardias, atrial flutter and atrial fibrillation are mainly associated with an underlying cardiac disease. The isolated forms of atrial flutter and fibrillation without any detectable cardiac disease are a diagnostic challenge and are associated with a relatively high rate of complications. AV node reentry and AV tachycardias with accessory path are not associated with cardiac disease; they occur in 0.8% of the population and can be assessed with satisfactory accuracy in respect of mechanism and risk by means of the 12-lead ECG alone. PMID- 8212747 TI - [Pharmacology of modern anti-arrhythmia drugs in therapy of supraventricular tachycardia]. AB - Prevention of recurrences of atrial fibrillation, slowing the ventricular rate during atrial fibrillation, and the acute management of atrioventricular junctional reentrant supraventricular tachycardia (paroxysmal supraventricular tachycardia) often require treatment with antiarrhythmic drugs. These drugs comprise a pharmacodynamically and pharmacokinetically heterogeneous group of agents whose individual properties determine correct use, contraindications and side effects. Stabilisation of sinus rhythm can be achieved with class IA and class IC sodium channel blocking drugs as well as with the class III agents amiodarone or sotalol. Verapamil, diltiazem, cardioselective beta-adrenoceptor blocking drugs or cardiac glycosides can be used to slow the ventricular rate during atrial fibrillation. Rapid termination of paroxysmal supraventricular tachycardia is achieved with i.v. administration of adenosine, verapamil, ajmaline, diltiazem, propafenone, or flecainide. If atrial flutter complicates the preexcitation syndrome, this type of supraventricular tachycardia must not be treated with calcium antagonists, cardiac glycosides or lidocaine, since these agents decrease refractoriness of the accessory pathway which may precipitate fatal ventricular fibrillation. PMID- 8212748 TI - [Current treatment of supraventricular tachycardia: drug therapy]. AB - Recurrent supraventricular arrhythmias are associated with palpitations, weakness, syncopes, etc. Pharmacological treatment with antiarrhythmic agents aims to interrupt the tachyarrhythmia episodes (acute therapy) and to stabilize sinus rhythm thereafter (chronic therapy). Due to the newer curative options (transvenous ablation), the segment for the pharmacological therapy is shrinking. Treatment with antiarrhythmic agents is still indicated, if the recurrence of tachycardia episodes can be sufficiently controlled by a well-tolerated antiarrhythmic regimen. In the cohort of atrial fibrillation, total mortality and mortality from cardiovascular causes were increased under the influence of quinidine. The risk must, therefore, be weighed against the anticipated benefit from as well as the likelihood of arrhythmia suppression, before treating a patient with class I antiarrhythmic drugs. In some cases, reduction of ventricular rate by calcium antagonists will be the better choice. In case of recurrent atrial fibrillation without or with minimal structural abnormalities, propafenone or flecainide are recommended. Sotalol, and in rare cases amiodarone, will be applied in coronary artery disease. Atrial fibrillation of recent onset may be interrupted by bolus injection of ajmaline, propafenone, or flecainide. In case of impaired cardiac function, intravenous amiodarone can be applied safely. In summary, the scientific basis for the treatment of supraventricular tachycardias has been strengthened by clinical trials. Careful evaluation of the individual patient is warranted prior to institution of the pharmacological treatment. PMID- 8212749 TI - [Electrotherapy of supraventricular tachycardia (atrial fibrillation/atrial flutter)]. AB - Contrary to patients with the WPW-syndrome and AV nodal reentry in whom radiofrequency catheter ablation is the therapy of first choice for cure from these arrhythmias instead of life-long medical therapy, pharmacologic therapy of atrial fibrillation and atrial flutter remains the treatment of choice in these patients. If, however, atrial fibrillation with rapid atrioventricular conduction is medically intractable and associated with severe haemodynamic impairment, these patients may be offered catheter ablation of AV conduction by radiofrequency energy. Compared to DC ablation, this approach is associated by an acceptable complication rate. Including the left ventricular approach in cases where it is not possible to ablate AV conduction using the venous approach, the success rate to achieve third degree AV block approaches 100%. With the development of temperature-controlled radiofrequency catheter ablation, a further reduction of side effects is anticipated. A disadvantage of this approach is the need for permanent pacemaker implantation (usually rate-adaptive VVI stimulation) after induction of complete AV block. Therefore, the advantage of normalization of ventricular rate by ablation of AV conduction has to be weighed against the risk of life-long pacemaker treatment for complete AV block in every patient. Patients with medically intractable typical atrial flutter may be offered the following alternative modes of electric treatment: selective ablation of the area of slow conduction sustaining circus movement in the right atrium underlying atrial flutter, by radiofrequency energy without interrupting AV conduction, implantation of a permanent antitachycardia pacemaker with electrodes positioned in the right atrium, radiofrequency catheter ablation of AV conduction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212750 TI - [Non-pharmacologic treatment of pre-excitation syndromes]. AB - Paroxysmal tachyarrhythmias due to accessory atrioventricular pathways are usually not completely suppressible with antiarrhythmic drug therapy. These patients can be treated by implantable antitachycardia pacemakers or surgical or catheter ablation of accessory pathways. The antitachycardia pacemaker offers a symptomatic treatment, which is indicated in patients with less often arrhythmias, without atrial fibrillation and with haemodynamically stable tachycardias. The surgical interruption of accessory pathways depends on thoracotomy and often the cardiopulmonary bypass. This therapy is a curative treatment, which is indicated in patients with further cardiac disease needing surgical intervention. Catheter ablation of accessory pathways with radiofrequency energy is the modern treatment. Our own experience with 12 patients with preexcitation syndrome and antitachycardia pacemakers, 50 patients with surgical interruption of accessory conduction and 63 patients with catheter ablation is referred and the results are discussed. PMID- 8212752 TI - [Risks and side effects in treatment of supraventricular tachycardia]. AB - Many new antiarrhythmic drugs effective in supraventricular tachyarrhythmia are now available. Since these compounds may lead to serious side-effects, the correct indication for the antiarrhythmic treatment has to be given regarding the ratio of risk and benefit. There is no doubt that aggravation of arrhythmia i.e. acceleration of tachycardia or even degeneration into ventricular flutter (including torsades-de-pointes tachycardia) and fibrillation may be related to the cardiac diagnosis depending on the extent of disease or left ventricular dysfunction and the presenting arrhythmia and possibly the electrophysiological effects of the drug. In general, negative inotropic effects of antiarrhythmic substances are overestimated; they may even be neglected as long as the antiarrhythmic agent leads to effective suppression of the symptomatic ventricular tachyarrhythmia. The best and most important consequence of the CAST study (Cardiac Arrhythmia Suppression Trial) showing an increase in mortality with antiarrhythmic drugs compared with placebo should be that physicians handle antiarrhythmic drugs now with more care than before. The problems with risks and side-effects in antiarrhythmic drug therapy of supraventricular arrhythmias underline the requirement for careful cardiological evaluation and monitoring in all patients receiving such drugs. PMID- 8212751 TI - [Anticoagulation: assessment of benefits and risks]. AB - Thromboembolism is a frequent complication of atrial fibrillation. As could be demonstrated by several placebo-controlled prospective studies in the recent years the rate of thromboembolism was reduced significantly by anticoagulation of nearly all kinds of atrial fibrillation. These results are challenging to weigh risks and benefits in every patient. The principles which have to consider in this calculation are discussed with regard to the knowledge derived from the controlled studies. PMID- 8212753 TI - [Contrast medium resorption in ERCP]. AB - During this study the absorption rates of two contrast media were measured in double-blind design. 33 patients received lopamidol (Solutrast 300), and 30 patients Meglumine iothalamate (Conray 60). A regular absorption of the contrast media during ERC, ERP and ERCP could be stated. With reference to the absorption rates a slight, but for statistically not significant advantage for the contrast medium lopamidol could be ascertained. During ERC the absorption rates ranged from 0.4 to 30%, during ERP from 2.2 to 18.8% and during ERCP from 1.0 and 30.0%. Consequently the endoscopist always has to take into account an anaphylactoid reaction due to the systemic absorption of contrast media which, compared to other examinations with contrast media, happens relatively seldom. PMID- 8212754 TI - [In vitro contractility of the musculature of human gallbladders with and without gallstones--relevance of the prostaglandin system for CCK regulated motoricity]. AB - This study describes the influence of endogenous and exogenous prostaglandins upon CCK-induced motility patterns of human gallbladders with and without stones (indomethacin and nocloprost; an exogenous PGE2-analogon). From 48 gallbladders with- and 22 gallbladders without stones (control group) longitudinal muscle stripes were dissected and transferred to an organ bath and CCK, indomethacin and nocloprost dose response curves were established. In another experimental protocol, the effect of CCK after indomethacin or nocloprost preincubation is demonstrated. Moreover, specimens of gallbladders were taken for histology and gallstones for analyse. The results demonstrate that gallbladders with stones have a significant higher basic tonus and phasic activities compared to the stone free controls. Because of these different responses to CCK, gallbladders of the stone-diseased group were divided in two groups: 64% of the gallbladders show a sensitivity and tonic response to CCK like the controls (contractors), 36% demonstrate a reduced sensitivity to CCK and only a slight tonic response (non contractors). Indomethacin causes a fall in tonus in both stone-diseased groups. It stops spontaneous activity in the contractor and non-contractor group. With indomethacin preincubation all three groups response to CCK with a significant reduced sensitivity. CCK-induced activity is reduced in the control and contractor group. In the non-contractor group, muscle strips do not contract after indomethacin preincubation. Nocloprost induces significant contractions in the control and contractor group. In both groups, the response to CCK after nocloprost preincubation is stronger than the reaction without preincubation. In the non-contractor group, a change in tonus after nocloprost application cannot be demonstrated, there also is no response to CCK after nocloprost preincubation. These results corroborate the notion of a significant contribution of the endogenous prostaglandin system to the regulation of gallbladder motility by CCK. PMID- 8212755 TI - Vero cytotoxin-producing Escherichia coli O157 infections in Austria. AB - To determine the prevalence of Vero cytotoxin-producing Escherichia coli (VTEC) serotype O157 associated diarrhea in the Austrian patient population, we surveyed all stool specimens of liquid consistency submitted to the Federal Public Health Laboratory (FPHL) in Innsbruck for 2 years for this organism. This laboratory serves a population of approximately 1 Million people. Of 5,265 stool specimens, 7 yielded O157 VTEC. Five isolates of E. coli O157 phage type 32, VT2 were cultured from specimens received during a three day period from residents in the county of Schwaz. During the investigation of this "outbreak" E. coli O157 strains were also isolated from two household contacts. Only 1 out of 8 persons with E. coli O157 diarrhea had bloody stools, although 5 of 7 tested specimens (= 71%) also yielded Campylobacter jejuni. None of our patients received antimicrobial therapy directed against E. coli O157 (one child had josamycin). There were no fatalities and no cases of hemolytic uremic syndrome (follow up period: 6 months). Consumption of hamburger, roast beef, and unpasteurized milk was not confirmed in this study. In Austria, no O157 VTEC strain was isolated till June 1992, although at the FPHL in Innsbruck stool specimens of liquid consistency were cultured for this organism since January 1991. PMID- 8212756 TI - [Prognostic value of long-term pH-metry in the B-II resected stomach]. AB - In a prospective study we investigated the clinical value of ambulatory 24-hour pH monitoring in the stomach after Billroth-II-resection. Recorded data of 10 patients with and 11 patients without ulcer recurrence after gastric resection were compared. The pH medians of the record periods "total time", "supine", "upright", "fasting" and "postprandial" were evaluated. Further the cumulative recording time of pH levels pH < 1, pH < 2, etc. was determined and compared in both groups. A pH median less than 2.8 "supine" indicated a postoperative ulcer recurrence with a sensitivity of 90% and specificity of 81%. A pH median less than 2.6 "fasting" predicted an ulcer relapse with a sensitivity of 90% and specificity of 72% (p < 0.001). In patients with ulcer recurrence pH was < 4 in more than 30% of total recording rime, pH < 5 in more than 45% and pH < 6 in more than 75% (sensitivity 90%, specificity 100%). According to these findings 24-hour pH monitoring seems to be useful for the prognostic assessment of the further course of ulcer disease after B II-surgery of the stomach. Thus pH monitoring results may be helpful in defining patient groups which may be candidates for acid reducing therapy to prevent ulcer recurrence. PMID- 8212757 TI - [Nizatidine in therapy and prevention of non-steroidal anti-rheumatic drug induced ulcers in rheumatic patients]. AB - 269 patients with various rheumatic disorders who had been treated with non steroidal anti-inflammatory drugs (NSAID) for at least three weeks, were enrolled in this randomised double-blind multicenter trial. Entry criteria were both the presence of an ulcer in gastric and/or duodenal mucosa (> 3 mm and < 20 mm in diameter) as well as dyspeptic symptoms. The patients had been treated with 150 mg nizatidine nocte (n = 86), 2 x 150 mg/d (n = 93) and 2 x 300 mg/d (n = 90) nizatidine. All patients continued to take their original NSAID-medication. The three nizatidine-groups had been well matched with respect to important patient characteristics. After 8 weeks of treatment more than 90% of gastric and duodenal ulcers had been healed under all three nizatidine-dosages. There was a tendency for higher healing rates in case of gastric ulcers after 4 weeks following the higher dose of nizatidine. Erosions in stomach and duodenum as well as esophagitis had been improved to a similar degree with all nizatidine doses. The same holds with respect to improvement of clinical symptoms such as epigastric pain, heartburn etc. Consumption of additional antacids was similar in all three groups. In the subsequent prophylactic trial 237/221 patients had been followed for 3/6 months. 116/107 received in addition to their continued antirheumatic medication nizatidine 150 mg nocte and 121/114 patients 2 x 150 mg nizatidine daily. The cumulative relapse rates within 6 months averaged 5.5% in the low and 1.8% in the high dose group (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212758 TI - Tuberculosis of the small bowel with perforation and hematogenous spread in a renal transplant recipient. AB - A 41-year-old male was admitted because of acute abdomen. A flat plate of the abdomen suggested pneumoperitoneum and a chest X-ray an infiltrate in the right upper lobe. The patient was a renal allograft recipient and was on immunosuppressive therapy with azathioprine, cyclosporine and steroids. At laparatomy inflammatory thickening of the bowel wall was found in the terminal ileum with necrotic areas and two sites of perforation. The involved terminal ileum was removed together with a right hemicolectomy. The resected segment showed exudative ileal tuberculosis and fibrinous and purulent peritonitis. During the postoperative period rapid hematogenous spread of tuberculosis developed with progressive reduction of respiratory function followed by ARDS. Autopsy revealed tuberculosis in all organs including the transplanted kidney. PMID- 8212759 TI - [Therapy of fecal incontinence from the internal medicine viewpoint]. AB - Despite a general belief is fecal incontinence a symptom rather than a diagnosis, usually occurring as a consequence of an underlying disease. Treatment of fecal incontinence, thus, is primarily treatment of this underlying disorder. If this causal treatment is not possible or effective, symptomatic treatment may become the goal. Furthermore, conservative management has to utilize all its possibilities before surgery may become a therapeutic option. This, however, is restricted by the limited number of conservative options available: Only a very few drugs act directly on the anal sphincter mechanism to increase the tone, all other medication may be contra-indicated. Laxatives are no treatment option at all in fecal incontinence, and the efficacy of electric stimulation of pelvic floor muscles has not been proven so far. Therefore, pelvic floor exercises have become treatment of choice, most effective with biofeedback support. This is supported by a variety of studies published in the past years. PMID- 8212760 TI - [Therapy of anal incontinence from the surgical viewpoint]. AB - Surgery of anorectal incontinence includes two essential forms: the traumatic lesion of the sphincter and the spontaneous proceeding incontinence. Both forms of incontinence require a surgical therapy that is concerned to its cause. Fresh traumatic lesions of the sphincter can be reconstructed directly by primary suture, elder, cicatrized lesions can be treated by doubling the sphincter or single reconstruction of internus and externus. In spontaneous proceeded incontinence, that requires a very detailed preoperative diagnostic, "post anal repair" and pubo-rectalis-plasy are therapeutic possibilities. By these surgical methods in most patients with incontinence it's possible to avoid a colostomy. PMID- 8212761 TI - [HLA-association of lymphocytic colitis: indications for an independent disease entity?]. PMID- 8212763 TI - [Use of endoscopy in stomach cancer and stomach polyps. German Society of Digestive and Metabolic Diseases]. PMID- 8212762 TI - [Chronic parenchyma ischemia and increased interstitial pressure in tissue- relevant factors in pathogenesis of chronic pancreatitis?]. PMID- 8212764 TI - [Clinic structure and timely management of emergency cesarean section--reference values and recommendations]. AB - GOAL: This retrospective clinical study was performed to analyze the relationship between the time course of an emergency Cesarean Section and the structural, logistic and circadian aspects of the clinical environment. METHODS: Statistical analysis was based on architectural and structural data from 132 Departments of Obstetrics in the region of Northrhine-Westfalia, Germany. Hospitals were compared in four groups of equal size defined by the number of deliveries per year. Data were available on 207 emergency C-Sections from 66 participating hospitals. The time of the day of each delivery was rounded to full hours. RESULTS: The size of the hospital was a highly significant predictor (p < 0.001) of the time elapsing between decision making and delivery (DD-interval) and of the preparation time required prior to the start of the operation: With increasing number of yearly deliveries the DD interval decreased from 31 minutes (SD = 15) to 19 minutes (SD = 7) with respective set-up times of 26 minutes (SD = 15) and 15 minutes (SD = 7) respectively. The time of the day had a significant influence on both variables (p < 0.05) with emergency C-Sections being slowest between 1:00 a.m. and 7:00 a.m. The mean time intervals observed may serve as a reference for the individual hospital situation: A preparation time of 15 minutes, time from start of surgery until delivery of 4 minutes and a DD interval of 19 minutes. CONCLUSIONS: The data presented in this study underline the importance of the immediate availability of a complete emergency team consisting of midwife, obstetrician, anesthesiologist, OR nursing staff and pediatrician. While not necessarily arguing in favor of a concentration of obstetrical practice in specialized centers, the following recommendations might be worth considering for any given clinical setting: 1. Immediate availability of a complete team is essential, especially during the night. 2. Well defined steps of urgency in agreement between all disciplines involved improve communication and save time. 3. The emergency C-Section in the delivery room may be a worthwhile alternative in the individual case. 4. Flexibility in the decision making process may increase efficiency. 5. Practice drills may help to identify weaknesses in the interaction and coordination of the team. 6. A functional hospital architecture is important to avoid unnecessary and uncontrollable delays. 7. Adequate training programs for the obstetrical team are essential with special emphasis on the early diagnosis of fetal distress and maternal complications. PMID- 8212765 TI - [Decrease in cerclage incidence in multiple pregnancies by vaginal ultrasound monitoring]. AB - Cervical insufficiency is a frequent complication particularly in case of multiple pregnancy and is often considered to be an indication for cerclage operation. We performed a vaginosonographic monitoring prospectively in 35 cases with multiple pregnancy in order to diagnose cervical insufficiency early and to perform cerclage operation when indicated. The results were compared with a group of 41 patients with multiple pregnancy who received prophylactic cerclage in other hospitals. No significant difference occurred concerning the duration of the pregnancy. In patients without prophylactic cerclage the frequency of preterm contractions was significantly lower, the frequency of premature rupture of membranes, however, was higher. Our results confirm the hypothesis that the application of a prophylactic cerclage does not improve fetal outcome in case of multiple pregnancy. Vaginosonographic as a single monitoring procedure seems to sufficient for the early diagnosis of cervical insufficiency. PMID- 8212766 TI - [Screening for fetal heart defects in the four chamber view with evaluation of larger arteries: possibilities and limits]. AB - The four-chamber view and the visualization of the root of the left and right ventricular outflow tracts has been proposed as a screening method for the detection of congenital heart disease in the fetus. In order to study the diagnostical value of the method we investigated 1600 fetuses between the 17th and 40th gestational week without anamnestic risk for congenital heart disease with this screening method in a two years' period. We found 33 fetuses to have an abnormality either in the four-chamber view or in the ventricular outflow tracts. The sensitivity of the method in the detection of congenital heart disease was found to be 81%, the specificity 99% and the positive predictive value 88%. Women at high risk for congenital heart disease in the fetus should still undergo a more detailed echocardiographic examination to maximize the sensitivity in the detection of structural heart defects. Nevertheless, the described screening procedure is an effective and feasible method to detect fetuses with severe congenital heart disease, whose prognosis may be improved by the delivery in a perinatological center. PMID- 8212767 TI - [Uterine activity in primiparous and multiparous women in spontaneous labor and induced labor with oxytocin]. AB - An analysis was performed of 5187 intra-amniotically measured labor pressure curves in 40 births with spontaneous labour (20 primiparae and 20 multiparae) and 40 births births in which labor was induced with oxytocin (20 primiparae and 20 multiparae). The dilatation of the os uteri was divided into three phases--Phase 1, dilatation of the cervix to 2 cm; Phase 2, dilatation of the cervix from 2 to 4 cm, and Phase 3, dilatation from 4 cm onwards until complete. During the active phase, from 2 cm until dilatation of the os uteri was complete, no differences were observed between induced and spontaneous labor with regard to frequency and amplitude of contractions. In the induced-labor cases, the parameters for uterine activity, maximum contraction and dilatation speed were higher in all three phases of labor, and those for total duration of labor lower than in the spontaneous labor cases. The contraction/dilatation speed is an important parameter for monitoring the effect of drug-induced stimulation of labor. In the latency phase in spontaneous labor, more contractions were observed in multiparae than in primiparae. This fact which should be reason enough to intensify monitoring of both mother and fetus during this phase. In light of these results it would appear advisable, in the absence of progress in labor, to make a clear distinction between the goals of cervical maturity and promotion of uterine activity, and to institute different drug therapy accordingly. PMID- 8212768 TI - [Effect of Listeria on contractibility of human uterine muscle]. AB - In Austria the prevalence of listeriosis is 2.6 cases per million inhabitants yearly, hence rather rarely the cause of spontaneous abortion or premature birth. On the other hand, Listeria monocytogenes is found in 1% of the asymptomatic population as a component of stool flora. Since the cause of premature labour contractions remains unclear in about half of all cases, we examined 29 listeria strains for their ability to cause myometrial contraction by direct contact using an in-vitro uterine strip-model. Seven of nine L. monocytogenes strains were able to cause contractions; contractions were not inducible by an nonhaemolytic mutane (SLCC 53, avirulent) nor by a rough strain (SLCC 5779, only slightly virulent). Three of six L. ivanovii isolates also exhibited the ability to induce contractions. None of the apathogenic species (L. innocua, L. seeligeri, L. welshimeri, L. grayi and L. murrayi) was capable of activating contractions in our in-vitro model. Only L. monocytogenes and L. ivanovii cause conjunctivitis after being dropped in rabbit's eyes (positive Anton Test). The influence of listeria on uterine activity as found in our in-vitro model thus correlates with the classical pathogenicity test. We consider these in-vitro results as an additional argument to oppose the presence of L. monocytogenes in ready-to-eat foods. PMID- 8212769 TI - [Antepartum prevention and postnatal therapy of respiratory distress syndrome]. AB - The introduction of surfactant in the therapy of respiratory distress syndrome (RDS) reduced mortality and long term complications in very premature infants. Nevertheless, the obstetric management influences critically the outcome. In a prospective study of 116 premature infants with RDS treated with natural surfactant preparations after birth, mortality was significantly reduced by antepartum corticosteroid therapy suggesting a synergistic effect of corticosteroids and surfactant on the immature lung. It is assumed that a preventive administration of surfactant immediately after birth would benefit neonates at risk for RDS more than a delayed surfactant replacement after the development of RDS. But without a reliable assessment of fetal lung maturity before birth more than 50% of our premature infants with birth weights less than 1500 g would be exposed to surfactant unnecessarily. It is important that fetal asphyxia is avoided. Acquired respiratory distress syndrome occur even in premature infants after shock or meconium aspiration and may respond poorly to surfactant replacement. This is also the case in lung hypoplasia or perinatal infection, where the combined efforts of obstetricians and neonatologists are needed to attain better results. PMID- 8212770 TI - [Primary hyperparathyroidism in the third trimester of pregnancy]. AB - A case of primary hyperparathyroidism in late pregnancy is described. After an initial conservative treatment surgery was performed in the 35th week of gestation. The further course of the pregnancy was uneventful, the newborn showed a normal development. PMID- 8212771 TI - [Blood flow in the umbilical artery in maternal hypotension and after therapy with Pholedrine longo--a Doppler ultrasound study]. AB - We performed a study in dopplersonography of the A. umbilicalis in pregnant women, who had either an untreated or a with Pholedrin longo (alpha receptor stimulating substance) treated hypotension. These study groups were compared with patients who had a normal blood pressure. In patients with hypotension we found higher values of the qualitative flow indices than women with normotension reflecting a low uterine perfusion. In the group with therapy of hypotension we could analyse a normalisation of the values without decrease of uteroplacental perfusion. These findings show, that hypotension is a high risk in pregnancy which we have to care for. PMID- 8212772 TI - [Fathers in the labor room--a survey before and after delivery]. AB - Meanwhile the attendance of fathers in the labour room is common. From 1. 7. 90 15. 10. 91 510 German fathers were interviewed before and 45' after labour. In comparison a smaller number (n = 56) of fathers were questioned who had decided not to attend. The evaluated data was split in the following three categories: 1. pre-post comparison; 2. "participants" and "non-participants" comparison; 3. special problems. The most mentioned reason for participation (over 85%) was the positive influence on the women. More then 70% of the attendants even wanted to support their wives during complicated delivery and surgical interventions. Approximately 5% of the fathers attending a clinic delivery would then prefer a home delivery because they more or less felt as a substitute to medical personnel. Non participants evidently were anxious due to missing preparation and information about the parturition. Sometimes the women desired no participation of their partners. About 23% of the men decided to attend labour just before birth. Practical recommendations are given and the change in the point of view of the fathers during course of labour is presented in this paper. PMID- 8212773 TI - [Indications for ambulatory therapy of alcohol dependence]. AB - The aim of the contribution is the discussion of client characteristics in regard to the indication of alcohol dependence outpatient therapy. In a first part issues of outpatient compared with inpatient treatment, in a second part results concerning indication criteria are presented. The third part shows differentiating factors in regard to the indication criteria and outcome of the clients. This part includes reabstinence, the ability to reach the goal of abstinence after relapse, the help of significant others, and arguments for the understanding of indication criteria in a broad sense. PMID- 8212774 TI - [Importance of chaos research for psychosomatic medicine]. AB - After a critical review of the many unsettled questions in psychosomatic medicine the author emphasizes the importance of the results of the so-called-research in mathematics, physics, biology and internal medicine. He developed various models for a deeper understanding not only of health and sickness but specially of the body/soul-problem and demonstrates the importance and fertility of the chaos investigation for the psychosomatic medicine. PMID- 8212775 TI - [Semantic activation phenomena in healthy probands and in schizophrenic patients. Analysis on the level of word pairs]. AB - Semantic priming in normal controls and schizophrenic patients can be demonstrated in lexical decision tasks. Data from such a lexical decision task are analyzed with special respect to the question as to whether associative processes in schizophrenic patients are characterized by the occurrence of entirely new associations or by the intrusion of normal associations, i.e., associations which can be found in normal subjects. The analysis of the semantic priming effects of single word pairs demonstrates little qualitative differences between the associations of normals and of schizophrenic patients. This finding provides further support for Maher's hypothesis of activated normal associations in schizophrenic patients. From a methodological perspective, the item-by-item analysis of lexical decision task data can be used to optimize this method. PMID- 8212776 TI - [Illness adjustment of adult patients with cystic fibrosis I. 1. Coping, personality and perceived health]. AB - The data of a coping-study of 46 adult patients suffering from Cystic Fibrosis is given. Due to several instruments of coping, personality and well-being and due to the fact, that coping with Cystic Fibrosis is here investigated for the first time with standardized coping-inventories, we emphasize high stability of coping, average values of personality, and well-being. Furthermore we can suggest several Clusters of an adequate coping with Cystic Fibrosis. PMID- 8212777 TI - [Illness adjustment of adult patients with cystic fibrosis II. 2. Social support and coping]. AB - As a part of our study of the coping with cystic fibrosis we examined the social network and the social support of adult patients. The results suggests that there is only little difference between women and men in the size of network and perceived support and that the family is of great importance as a source of support. Compared with healthy adults, perceived social support seems to be less but greater than for depressive patients. Only some coping-clusters do correlate positively with social support. PMID- 8212778 TI - [Stored intracardiac electrograms: accuracy of arrhythmia classification in patients with cardioverter/defibrillator system]. AB - A cardioverter/defibrillator that is capable of storing endocardial electrograms before and after electrical device therapy was implanted in 29 patients presenting drug refractory ventricular arrhythmias. During a follow-up period of 7.5 +/- 4.6 months 15/29 patients (51%) experienced a total number of 112 pulse generator discharges. In 104 arrhythmia episodes the stored electrogram was analyzed. Morphological criterias of the stored electrogram as detectable P-waves and changes in the QRS-morphology during tachycardia compared to sinus rhythm served for classification of the documented arrhythmia. The analysis of the stored electrogram established a definitive diagnosis of the arrhythmia and allows to distinguish supraventricular arrhythmias from ventricular arrhythmias in every episode. 72/104 (69.2%) of the discharges were classified as appropriate, 32/104 (30.8%) of the device discharges were not appropriate and caused by atrial fibrillation and flutter, sinustachycardia and AV-nodal reentrant tachycardia. In two patients device discharges caused by a sensing malfunction ot the pulse generator was detected by the analysis of the stored electrogram. The new diagnostic feature of stored electrogram shows a high accuracy of rhythm classification and represents a major advance in the treatment with cardioverter/defibrillators. PMID- 8212779 TI - [The automatic implantable cardioverter-defibrillator for prevention of sudden heart death in children and adolescents]. AB - Little experience exists with the automatic implantable cardioverter defibrillator in the pediatric population. Since 1990, an automatic implantable cardioverter defibrillator was implanted in four young patients (mean age 15.8 years, mean body weight 53.3 kg) with life-threatening ventricular tachyarrhythmias at our institution. In three patients, a cardiac anomaly was evident (dilated cardiomyopathy, status post Rastelli operation for complex transposition of the great arteries, status post atrial switch for transposition of the great arteries), the last patient had a normal cardiac anatomy. Indications for implantation were resuscitation from documented hypotensive ventricular tachycardia in one patient and recurrent syncope of suspected cardiac origin in the remaining three patients. At preimplantation electrophysiological study, all four patients had inducible ventricular tachycardia and/or ventricular fibrillation. At implantation of the cardioverter defibrillator in the operating theatre, the ventricular tachyarrhythmias were again induced and terminated reliably by the device. After a mean follow-up of 13 months, three of the four patients had appropriate discharges without syncope or resuscitation. The automatic implantable cardioverter-defibrillator appears to be a feasible and effective therapy also in pediatric patients for prevention of sudden cardiac death due to ventricular tachyarrhythmias. PMID- 8212780 TI - [Electrocardiography and electrophysiologic findings in patients with myotonic muscular dystrophy]. AB - Myotonic dystrophy is associated with diffuse cardiac conduction disturbances. Seven consecutive patients, all asymptomatic with respect to cardiac abnormalities, were investigated by means of ECG, Holter monitoring, and invasive electrophysiologic studies (EPS). During Holter monitoring, no abnormalities were found in any patient, except for one patient who showed single monomorphic VEBs. During EPS three patients showed conduction disturbances in the AV-node (AVN) as well as in the His-Purkinje-system (HPS) in another three patients. Except for two patients ventricular vulnerability was normal during programmed ventricular stimulation. A considerable number of asymptomatic patients with myotonic dystrophy reveals AVN- and HPS-conduction disturbances as shown during EPS. PMID- 8212781 TI - [Diastolic flow analysis of the left ventricle after myocardial infarct]. AB - The diastolic function of the left ventricle was investigated in 12 normal young volunteers, 10 older volunteers, 10 patients without evidence of coronary artery disease, 26 patients with inferior wall and 19 patients with anterior wall infarction at eight locations of the total circumference of the left ventricle using pulsed wave Doppler. The ratio of early diastolic inflow (Vmax E) to the maximal velocity of atrial contraction (Vmax A) was determined. Furthermore, the delay between the end of electrical diastole until the end of the A-wave of the pulsed Doppler was measured. The results were compared with a clinically used marker of myocardial ischemia, treadmill exercise testing. The E/A ratio was 2.03 +/- 0.51 in normal volunteers, 1.16 +/- 0.41 in older volunteers, 1.41 +/- 0.59 in patients without evidence for coronary artery disease, 1.28 +/- 1.13 in patients with inferior and 1.08 +/- 0.41 in patients with anterior wall infarction (p = 0.020 ANOVA). The diastolic delay at the apex was 47.3 +/- 8.9 ms in normal volunteers, 78.3 +/- 8.3 ms in older volunteers, 79.1 +/- 13.7 ms in patients without coronary artery disease, 109.1 +/- 12 ms in patients with inferior and 169.5 +/- 18.8 ms in patients with anterior wall infarction (p = 0.000 ANOVA). There was a correlation between the latter parameter of delay and the amount of pathological wall segments at wall motion analysis (r = 0.61, p = 0.007). In two patients with anterior myocardial infarction (11%) with significant diastolic delay intraventricular thrombi developed consecutively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212782 TI - [Cellularity and ultrastructural characteristics of human atherectomy specimens: comparison between restenosis and primary stenotic tissue of coronary and peripheral lesions]. AB - Restenosis in patients treated by angioplasty is clinically and angiographically defined. The question remains to which extent each restenotic lesion can be attributed to residual plaque material and/or neointimal tissue formation post primary intervention. In an effort to reveal distinct anatomical characteristics which may allow conclusions to pathogenetic mechanisms involved in restenosis, histopathologic and electron microscopic examinations of human restenotic tissue were performed. To compare tissue samples from clinically restenotic lesions with those from untreated primary lesions for cell number and ultrastructural characteristics, a total of 64 percutaneously excised tissue specimens from coronary (n = 9) and femoral lesions (n = 18) of 27 patients treated by directional atherectomy were analyzed. Semiquantitative assessment of plaque slices for cell number (12 fields of view/lesion; magnification x500) revealed a spectrum of 11.7 to 35.3 cell nuclei/field of view (C/F) for clinical restenoses (n = 10) and of 0.9 to 28.2 C/F for primary lesions (n = 17). When comparing tissue specimens from restenotic origin with those of native lesions, there was a highly significant (p < 0.001) difference in cell number (ave: 22.2 +/- 7.1 versus 8.6 +/- 7.9 C/F; x +/- SD). Hypercellularity (mean cell density defined with > 20 C/F) was observed in 6/10 restenoses, hypocellularity (< 10 C/F) in 0/10 restenoses. For primary lesions, hypocellularity was found in 10/17 lesions, but hypercellularity in 2/17 lesions. Ultrastructural analysis of hypocellular lesions by transmission electron microscopy revealed large extracellular matrix fields with infrequently embedded smooth muscle cells (SMCs). These cells were characterized by a microfilament-rich intermediate phenotype, thereby indicating decreased metabolic activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212783 TI - [Dobutamine versus dipyridamole magnetic resonance tomography: safety and sensitivity in the detection of coronary stenoses]. AB - Safety and sensitivity of gradient-echo magnetic resonance imaging (MRI) for the identification of significant coronary artery stenoses using pharmacologic stress testing was assessed in 61 patients with > or = 70% stenosis of a major coronary artery and a normal left ventricle. After MRI at rest 28 patients underwent dobutamine-MRI during steady-state dobutamine infusion (5, 10, 15 and 20 micrograms/kg/min) and 33 patients had dipyridamole-MRI after high-dose dipyridamole infusion (0.75 mg/kg over 10 min). All patients additionally performed standard ECG exercise stress testing (EST). Segmental wall motion analysis was performed in basal and midventricular short axis tomograms by two observers. A segment was graded pathologic if transient dobutamine or dipyridamole induced wall motion abnormalities could be detected. For comparison to coronary angiography findings, each segment was assigned to one of the coronary artery perfusion territories. There were no serious side-effects during dobutamine and dipyridamole infusion leading to termination of the study protocol. Peak double product during dobutamine infusion was significantly higher (p < 0.001) than after dipyridamole infusion (18.493 +/- 4.311 versus 12.799 +/- 2.694 mm Hg/min). Overall sensitivity of dobutamine and dipyridamole-MRI for coronary artery disease (CAD) was 85% and 84%. Regional asynergy by dobutamine and dipyridamole-MRI was observed in 73% versus 79% patients with single- and 100% versus 92% with multi-vessel disease. Individual coronary artery stenoses were correctly identified by segmental wall motion abnormalities in 87% versus 81% for left anterior descending, 62% versus 86% for left circumflex and 78% versus 92% for right coronary artery stenoses. In conclusion, dobutamine and dipyridamole-MRI are well tolerated and safe non-exercise dependent tests for detection and localization of hemodynamically significant coronary artery stenoses with a similar diagnostic accuracy but with a better control of stress intensity and duration provided by dobutamine. PMID- 8212784 TI - [Percutaneous transluminal coronary angioplasty in coronary multivessel disease: clinical course in relation to degree of functional revascularization]. AB - In this prospective nonrandomized study, we analyzed the influence of the degree of revascularization--determined by anatomic, morphologic, and functional criterias--on clinical follow-up after PTCA in patients with multivessel disease. 283 patients (74% with double vessel disease, 26% with triple vessel disease; mean age 59.2 +/- 8.2 years; 250 (88%) men) were treated. Clinical successful PTCA was achieved in 247 patients (87.2%): in 239 patients (84.4%) all attempted lesions and in 8 patients (2.8%) at least the culprit lesions were successfully dilated. Complications were seen in 15 patients (5.3%): seven patients underwent emergency bypass surgery, one patient had bypass surgery 8h after PTCA because of an early re-occlusion, five patients suffered an acute myocardial infarction during PTCA, and two patients, who had PTCA because of cardiogenic shock, died during PTCA. Post PTCA, 39 patients (13.8%) had anatomic complete (AK), 35 patients (12.4%) anatomic incomplete but functional complete (FK), 148 patients (52.3%) anatomic incomplete but functional adequate (FA), and 46 patients (16.2%) anatomic and functional incomplete (IR) revascularization. All patients had follow-up after 30.5 +/- 5.5 months. Fifteen patients (5.3%) died, 15 patients (5.3%) suffered a myocardial infarction, and 39 patients (13.8%) underwent an elective bypass operation during follow-up. Cumulative 2-year survival and cumulative 2-year infarct-free survival were not influenced by the degree of revascularization. In contrast to that, the cumulative 2-year bypass-free survival was significant lower in patients with IR (71.0%) compared to patients with AK (92.5%; p < 0.01), FK (89.3%; p < 0.05), and FA (92.7%; p < 0.001). Patients with IR were more likely to have PTCA of previous untreated lesions and were often less likely to have clinical improvement compared to the other subgroups. Thus, in patients with multivessel disease PTCA is a therapeutic option if AK, FK, and FA revascularization can be achieved. Provided that just an IR revascularization can be achieved by PTCA, angioplasty should be performed only for treatment of acute ischemic syndromes in order to improve clinical symptoms. Otherwise, an increased incidence of further revascularization procedures and a reduced clinical improvement can be expected. PMID- 8212785 TI - [Early hemostasis after coronary therapeutic interventions by using a collagen plug]. AB - Significant bleeding at the puncture site is one of the most important problems in the care of patients undergoing interventional coronary procedures like PTCA, rotablation, laser angioplasty or stent implantation. This is due to systemic application of heparin, acetylic salicic acid and, in stent patients, even additional coumadine. Furthermore, the interventional systems implement catheter systems with a large inner and outer lumen leading to increased vessel trauma. To decrease the risk of bleeding and to reduce the time of pressure dressing and bed rest, a bovine collagen plug (VasoSeal) was used in 600 consecutive patients undergoing one of the above-mentioned interventional procedures. In the majority of patients (pts.) (474/600 = 79%) either no (404 pts.) or minimal (70 pts.) bleeding occurred. Bed rest could be reduced from more than 24 h to 6-12 h. In 65/600 pts. (11%) significant bleeding developed which could be controlled by compression. Bed rest in these patients was 13-20 h. Larger bleedings or complications occurred in 61/600 pts. (10.2%) and could be controlled conservatively in all but eight patients. One patient (0.2%) had a narrowing of the artery at the puncture site after the procedure, probably due to intraarterial plug application. In another patient (0.2%) embolization of the plug into the popliteal artery occurred which could be treated by embolectomy using a Fogarty-catheter. Arteriovenous fistulae or aneurysms developed in 8/600 pts. (1.3%) but these are no specific complications of the hemostatic device. The plug could not be placed in 13/600 pts. (2%), mainly in the beginning of the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212787 TI - [Biology of aging]. PMID- 8212786 TI - [Coronary stent implantation: infection and abscess with fatal outcome]. AB - We report a case of coronary stent-implantation using a Palmaz-Schatz-stent in the right coronary artery (RCA) of a 66-year old woman. Coronary stenting was performed following local dissection and high-grade stenosis after PTCA. Following stent thrombosis re-PTCA was successful, but within 4 weeks progressive reduction of the patient's general condition, plus leucocytosis, subfebril temperatures, and a pericardial effusion occurred. Transesophageal echocardiography documented a perivascular myocardial abscess near the RCA stent; puncture demonstrated pericardial empyema. Emergency cardiac operation was done with segmental resection of the destructed RCA, stent explantation, and CABG to the peripheral RCA, but the patient died. To our knowledge, this is the first case of stent infection reported in the international literature. Transesophageal echocardiography was very helpful in diagnosing this fatal complication of coronary stenting. PMID- 8212788 TI - [Unit-free mathematical values of aging]. AB - From a mathematical model of aging are deduced three unit-free numbers. It is possible to calculate a critical value of the number beta t, where beta means the aging rate and t the chronological age of the organism. If beta t is greater than 1.84, then the theoretical life span is reached. Using an iteration method another unit-free number, namely, the quotient x of the growth rate and the aging rate beta is calculated to x = 4.5. PMID- 8212789 TI - Intracellular interactions under oxidative stress and aging: a hypothesis. AB - Oxygen-derived free radicals may result from various reactions, both intra- and extracellularly, but generation of oxygen free radicals from electrons escaping from the electron transport chain in mitochondria is by far the predominant process during the lifetime of a "normal", healthy cell. There is clear evidence that mitochondria are also an important target for oxygen-derived free radicals, and the resulting mitochondrial malfunction has long been suggested as the intracellular basis of aging. Moreover, there is clear evidence that free radical dependent reactions lead to lipofuscin formation and its accumulation in Lysosomes of post-mitotic cells. Lipofuscin accumulation was demonstrated to be dependent on the probability of iron-catalyzed Fenton reactions. A hypothesis is presented which assumes free radical dependent reactions in mitochondria and lysosomes to be interdependent. Production of hydrogen peroxide in mitochondria and its subsequent diffusion in the cytoplasm, and Fenton reactions in lysosomes, transferring hydrogen peroxide intra-lysosomally to the highly cytotoxic hydroxyl radical, are thought to be necessary intermediary steps in the generation of mitochondrial damage. On the other hand, damage to mitochondria increases both mitochondrial output of hydrogen peroxide and lipofuscin accumulation. PMID- 8212790 TI - [Age-dependent changes in mRNA transport (nucleus-cytoplasm)]. AB - Transport of mRNA from nucleus to cytoplasm is an ATP-dependent process which occurs strictly vectorially. Because the mRNA is structurally bound during transport, mRNA transport is a "solid-state" process consisting of i) mRNA release from the nuclear matrix, ii) mRNA translocation through the nuclear pore, and iii) cytoskeletal binding. We identified and purified the following components involved in the translocation step: i) the nuclear envelope (NE) nucleoside triphosphatase (NTPase) which is stimulated by the 3'poly(A) tail of mRNA, ii) the poly(A)-recognizing mRNA carrier, iii) the NE protein kinase, and iv) the NE phosphatase. In addition, we found that an RNA helicase activity is present in NE, which also may be involved in RNA transport. Our results show that, besides poly(A), also double-stranded RNA structures may modulate RNA export. The amount of mRNA released from nuclei markedly decreases with age. Evidence is presented that this age-dependent change is caused by an impairment of polyadenylation of mRNA, hnRNA processing, release of mRNA from nuclear matrix, and translocations of mRNA from nuclear to cytoplasmic compartment (decrease in activities of NE NTPase, protein kinase, and phosphatase; decrease in poly(A)-binding affinity of mRNA carrier). PMID- 8212791 TI - [Age-dependent changes in "intracellular immunity" to virus infections]. AB - A study of the antiviral 2',5'-oligoadenylate (2-5A) system in different tissues of rats of different age (newborn: 1-day old; young adult: 2-3 month old; middle aged adult: 12-month old; and old: 32-33-month old) revealed that the activities of the 2-5A metabolic enzymes alter during aging and development. We demonstrate that soluble 2-5A synthase (2-5OAS) activity strongly increases after birth, reaching maximal levels in young adult and middle-aged adult animals, and then significantly decreases with age. In contrast, the activity of 2',3' exoribonuclease which inactivates 2-5A increases by three-fold with age. The decrease in 2-5OAS activity and increase in 2-5A nuclease activity were found to result in a decrease in the cellular 2-5A content with age. The 2-5A-dependent ribonuclease (RNase L), which degrades viral RNA, also changes age-dependently. The amount and activity of this enzyme were determined in cross-linking experiments, in nitrocellulose binding assays; and in the ribosomal RNA cleavage assay. The livers of old rats display a 5-6-fold decrease in RNase L activity compared to the adult animal groups, while the amount of the enzyme does not change significantly during aging, with the exception of a drop by 30% in the nuclear matrix fraction. We conclude that the antiviral activity of the 2-5A system is impaired in old cells with the consequence that virus production cannot be efficiently suppressed. PMID- 8212792 TI - [Effect of cytoplasmic factors on cell nucleus binding of glucocorticoid receptor complexes in the rat liver of two age groups]. AB - The nuclei binding of activated glucocorticoid receptor complexes (GRC) was significantly diminished in old, unstressed rats compared with young ones. In animals killed at different times after physiological stress there were no significant age-dependent differences in nuclei binding of GRC, which recurred in the cytoplasm after 60, 120 and 180 min, resp. Addition of Ca2+ and ATP, resp., to the incubation system increased the nuclei bound part of GRC, especially in young animals. ATP-stimulated translocation promoter (ASTP), isolated from rat liver cytosol, raised the nuclei binding of GRC in both age groups, whereby the increase was only significant in young animals. In cytosol of old rats ASTP were found in a lower concentration; moreover, the reaction between ASTP, GRC, and the template seems to be impaired. PMID- 8212793 TI - Stimulatory effects of ascorbic acid on hyaluronic acid synthesis of in vitro cultured normal and glaucomatous trabecular meshwork cells of the human eye. AB - The outflow of aqueous humor of the primate eye occurs across the filter system of the trabecular meshwork (TM) into Schlemm's canal. Cells of TM derived from a normal (TM-N-cells) and a glaucomatous human eye (TM-G-cells) were established in monolayer culture. The present comparative experiments were performed with cells kept in a defined serum-free medium (the aqueous humor is nearly protein-free!). Under these conditions the cells stay alive for several months in a non proliferating state. TM-G-cells exhibited a lower synthesis rate of glycosaminoglycans-especially of hyaluronic acid (HA)--than TM-N-cells. Addition of 50-200 micrograms/ml ascorbic acid (the aqueous humor is characterized by a high ascorbic acid concentration of about 150 micrograms/ml) to the culture medium resulted in a significant dose-dependent stimulation of HA-synthesis and secretion, which was relatively stronger in case of TM-G-cells than with TM-N cells. Thus, the results suggest a role of ascorbic acid in the probably membrane localized HA-synthesis. Functions of ascorbic acid and HA for the morphological and functional integrity of the TM-cells in vitro and the outflow apparatus in vivo were discussed. PMID- 8212794 TI - [Age-related changes in systematic inhomogeneities of articular cartilage]. AB - We have considered the question of the quantification of differentiation processes. We investigated articular cartilage of the Caput femoris in 22 cases aged from 0 to 77 years. We measured cell size and volume density. During aging a shifting of the layer with the maximum cell size in relation to the joint surface as well as the formation of two layers with different volume densities take place. We believe that the changes in nutritional and load conditions during life play a role in these processes. We describe these with the term "diversification", characterizing the process of the changing of the degree of structural order. PMID- 8212796 TI - [Age-related changes in lipid metabolism parameters: screening studies on a population basis]. AB - Measurement of concentrations of total cholesterol, high density lipoprotein (HDL)-cholesterol and Lp(a) was carried out within a screening project on population basis including 3014 men and 5529 women of the town Leipzig. The age of the participants varied from 18 to 99 years. The aim of this population-based strategy was to identify individuals with elevated risk with regard to atherosclerotic diseases. There is an age dependence with a maximum of the ratio total cholesterol/HDL cholesterol in the age group 61-70 years. Between the ages 50 and 70 years, mean total cholesterol levels in women exceed those of men. Postmenopausal women show higher Lp(a) concentrations than premenopausal women. The observed age dependence of lipid profile may be the result of both intrinsic as well as of environmental factors which are characteristic for industrialized societies. PMID- 8212795 TI - Transport and production of cerebrospinal fluid (CSF) change in aging humans under normal and diseased conditions. AB - In three control groups of lumbar (L), cisternal (C), and ventricular (V) cerebrospinal fluid (CSF) with prealbumin contents of ventricular origin (CSF-V prealbumin) within the reference range, indications for an increased transport of V-CSF into spinal space are presented in the elderly as well as an elevated production of V-CSF. Indications for a diminished V-CSF production, respectively, an increased transport of CSF-V-prealbumin into the spinal space were found in elderly patients suffering from diverse CNS diseases. As these alterations proved to be not disease-specific, the age-related increase of CSF transport was discussed with respect to brain atrophy and enlarged CSF spaces in the elderly central nervous system (CNS). CSF serum prealbumin content, an indicator of blood brain-barrier function, increased with age similarly to albumin in the "normal" elderly, respectively with diverse CNS diseases. Age- and disease-related decreases of albumin and prealbumin contents in blood serum may lead to wrong interpretations. PMID- 8212797 TI - [The dynamics of aging of an unselected population of limited representation]. AB - Aging rates of a sample which should represent the total population living in a district of Madrid were studied using the vectorial calculation as a mathematical model. The number of individuals who finally participated was 867, homogeneously distributed by sex and age decades in the age range of 20-100 years. A total of 15 variables was applied, but they were deduced from health-related data obtained from a special elaborated questionnaire. The resulting aging factor--a dimension to evaluate the aging acceleration--agrees with the corresponding results of biological aging studies previously published. Moreover, we contend that the obtained information from the simply sent questionnaire is accurate and of biological value, and would enable studies on the aging rates of populations. PMID- 8212798 TI - [Use of psychopathometric procedures in diagnosis of dementia exemplified by a comparison between the Mini-Mental State and the MWT/KAI (Multiple-Choice Vocabulary/General Intelligence Test Short-Form) test system]. AB - Different definitions of dementia have resulted in various psychopathometric diagnostic instruments. For that reason, the validity of the test or test battery is related to the originating definition of dementia. There are short tests which can be easily handled (e.g., Mini-Mental State or the test battery Multiple Choice-Vocabulary-Intelligence Test/Short Test for General Intelligence). These tests can be used for the verification of a severe intellectual and mnemonic deterioration or a relative decrease of the mental capacity. For their objectivity, reliability and validity they are suitable for diagnostic routine. However, two aspects should be taken into consideration: Before using psychopathometric tests which aim at objectifying a decrease of mental capacity and indicating the degree of severity, it is necessary to make a differential diagnosis for particularly excluding so-called pseudodementia. It is also a fact that a single test is not sufficient for registering each degree of severity. The Mini-Mental State test can be used for documenting moderate to severe cases of dementia. The test battery Multiple-Choice-Vocabulary-Intelligence Test (MWT)/Short Test for General Intelligence (KAI) is suitable for the diagnosis and follow-up of mild to moderate cases. PMID- 8212799 TI - [Obesity and diabetes in the aged--correlation and relation to some chronic diseases]. AB - The authors analyzed obesity in 1173 persons aged 75+. They were all inhabitants of the same section of the town of Brno, CSFR, 721 of them were diabetic and 452 non-diabetics. The authors concentrated on the internal analysis of both groups regarding obesity; they found it to occur much more frequently among the diabetics (p = 0.005). The difference in obesity occurrence between men and women was found to be significantly higher among diabetic women (p = 0.005). The authors also analyzed the relation of obesity to the occurrence of coronary heart disease, hypertension, cerebrovascular incidents, and chronic pyelonephritis. Higher values were found for both hypertension in obese non-diabetics (p = 0.005) and cerebrovascular incidents in obese diabetics (p = 0.025); other differences were not statistically significant. The authors compared cholesterol levels of both groups; the results are unfavorable for the obese diabetics (Table 2); only the difference between non-obese diabetics and the obese non-diabetics was not statistically significant. The authors also compared treatment regimens for obese and non-obese diabetics. A significant difference was found for diet, by which the non-obese diabetics were more frequently treated (p = 0.05). PMID- 8212800 TI - Cumulative prevalence of urinary characteristics in very old people. AB - We studied in 1982 six urinary characteristics in very old inhabitants of Tampere, Finland, born in 1892 or earlier (N = 167). The majority (N = 132) of the subjects had also been studied in 1977 and 1978. The abnormalities were quite transient during the 5-year period. The cumulative percentage of those who had urinary infection was high in respect of bacterial culture and pyuria. Positive bacterial culture (> or = 10(5)/ml) could be detected in over half of the cohort, and pyuria (> 5/HPF) in 76%. Although persistence of albuminuria and haematuria was individually relatively rare in all three surveys, their cumulative percentages were 36% and 34%, respectively, during the 5-year period. Use of indwelling catheter was significantly more frequently connected with bacteriuria and haematuria than with albuminuria or pyuria. PMID- 8212801 TI - [Orthostatic hypotension with syncope--a problem of hypertensive therapy in the aged]. AB - In 12 of 32 elderly (> 65 years) hypertensives admitted with syncope, a diagnosis of orthostatic hypotension was made after a positive orthostatic tolerance test and extensive diagnostic evaluation with exclusion of other causes of syncope. Blood pressure of these 12 patients (pts.) after admission was 145 +/- 16/83 +/- 6 mmHg; at that time the pts. were treated with 2.6 +/- 1.6 different antihypertensive agents, and 67% of the pts. received a combination therapy. After reevaluation of treatment the pts. could be discharged with 1.3 +/- 0.7 different antihypertensive agents (significant difference, p < 0.02); in 25% of pts. (p < 0.05) combination therapy was still necessary. Before discharge casual blood pressure was 156 +/- 17/85 +/- mmHg (with the patient in the sitting position); average daytime ambulatory blood pressure was 145 +/- 18/80 +/- 5 mmHg. Three months after discharge 91% of pts. remained free of a new syncope. Orthostatic hypotension is a frequent cause of syncope in the hypertensive elderly; thus, their blood pressure should be checked more often in the sitting and standing position and by ambulatory monitoring. PMID- 8212803 TI - [Sonographic diagnosis in injuries of the shoulder joint]. AB - The value of sonography for diagnosis of injuries of the acromioclavicular joint was examined in a prospective investigation. In 22 successive patients sonography was used in two defined positions, the results were compared with standard X-rays under weight loading. Only in 9 cases the findings could be controlled during operative exploration. In 16 cases, sonographic and radiologic findings were corresponding, in 6 cases both methods lead to different results. In all corresponding cases sonography was able to demonstrate direct or indirect signs of the damage of acromioclavicular and coracoclavicular ligaments. In the operatively controlled group in all cases the sonographic diagnosis was confirmed. PMID- 8212802 TI - [Biomechanical principles in diarthroses and synarthroses. II: The humerus articulation as a ball-and-socket joint]. AB - The shoulder joint does not represent a simple ball-and-socket joint with three degrees of freedom unlike widely believed. Series of X-ray pictures show that in abduction the momentary rotational axis does not meet the center of the humerus. Morphological measurements yield the result that the radius of curvature of the cavitas is slightly greater (2 mm) than the humeral one. This physiological incongruity of the articulating surfaces is functionally necessary. Thus, the shoulder joint represents a force-locked dimeric ball-and-socket joint. In abduction e.g. the humerus simultaneously rotates around the humeral center and around the cavitas center in opposite direction. The resultant momentary rotational axis is therefore shifted towards the scapula as in vivo measurements confirm. Fundamental kinematical and statical properties of the joint are derived which explain substantial experimental finding in literature. PMID- 8212804 TI - [Can ultrasonography be used to measure torsion angle of the humerus? Comparison of ultrasonographic, computerized tomographic and anthropometric methods]. AB - Sonographic measurements on 40 cadavaric humeri of the angle of torsion according to Harland had been performed. The results were referred to different computertomographic and anthropometric methods. Sonographic measurements proofed to be accurate and were easily reproducible. Comparing sonographically detected angles with the anthropometric results there was shown a mean difference of 28.9 degrees +/- 7.8 degrees. We conclude that sonography is able to give accurate and reproducible results that do not exactly reflect the angle of torsion. PMID- 8212805 TI - [Differential diagnosis of shoulder pain: chronic neuropathy of the suprascapular nerve]. AB - Suprascapular neuropathy may present with chronic shoulder pain and weakness of abduction and external rotation of the arm. Therefore, it should always be included in the differential diagnosis of shoulder pain. Usually, the nerve is compressed at the suprascapular notch or the spinoglenoid notch. Here, the nerve is relatively fixed. In the etiology, repeated and forceful movements around the shoulder joint, especially in athletes such as volleyball players, are considered to be frequent causes of suprascapular nerve damage, whereas ligament hypertrophy and ganglia are uncommon. If conservative therapy fails, surgical decompression of the nerve is required for relief of pain and resolution of weakness. PMID- 8212806 TI - [Stress on the rotator cuff sutures in relation to joint position]. AB - In a vitro study we evaluated the influence of surgical technique on the postoperative tension of the supraspinatus tendon in rotator cuff ruptures. In ten shoulder specimens Hall-Effect Strain Gauge (HEST) were implanted in the supraspinatus tendon close to the insertion at the humerus. We documented the tension in specimens with intact rotator cuff as well as after reconstruction of small and large tears in different joint positions. In the specimens with an intact rotator cuff there was almost no tension registered. Only in adduction with external rotation and flexion we found slightly increased values. After reconstruction we found the highest tension in adduction, flexion, and external rotation of the humerus. Release of the coracohumeral ligament resulted in a decrease of tension in flexion and external rotation. Whereas in extension coracohumeral ligament release had no influence on the tension of the tendon. However, after complete capsule release the tension in extension also decreased. CLINICAL RELEVANCE: If mobilisation in cases of rotator cuff reconstruction is necessary we recommend first release of the coracohumeral ligament in small and moderate tears. In major tears a complete capsule release is necessary. During physical therapy in the early postoperative course, flexion in the adducted and externally rotated arm should be avoided. PMID- 8212807 TI - [Cancellous metal implant in the surgical treatment of recurrent post-traumatic shoulder dislocation]. AB - After a short abstract about history and principles in the operative treatment of recurrent dislocation of the shoulder joint and after an illustration of disadvantages and complications in the operative technique described by Eden Hybinette-Lange, which is favoured in the German speaking area, we are introducing a modification of this technique by use of an implant made from cancellous metal "Lubeck" instead of a bone block. In addition to the introduction of this new technique, first results in 14 patients undergoing this operation are shown up. PMID- 8212808 TI - [Sternocostoclavicular hyperostosis--case reports and differential diagnosis]. AB - Sternocostoclavicular hyperostosis (SCCH) is a disorder related to collagenoses. SCCH is typically characterised by the triad of swelling of the sternoclavicular and/or sternocostal joints of the first or second rib, palmar and plantar pustulosis (PPP), only limited elevation of inflammation indicating laboratory parameters. Till today the etiology is unclear and no causal therapy is known. Symptomatic treatment consists of administration of NSAID and cortisone, irradiation and even limited resection of the clavicle and rib. PMID- 8212809 TI - [Arthrolysis and arthroplasty of the elbow joint. A comparison of surgical results between children and adults]. AB - Because of stiffness of the elbow joint until 1988 146 operations have been done in 132 patients on the Department of Orthopaedic Surgery in Heidelberg. 55 procedures have been done in children and adolescents younger than 16 years, 91 times in adults. In both groups posttraumatic stiffness and stiffness of other origin have been treated. Procedures have been mobilisation in anesthesia, simple or enlarged arthrolysis as well as arthroplasties. Results have been evaluated by the method of Cauchoix and Deburge (relative gain of range of movement). In nontraumatic stiffness of the elbow younger patients under the age of 16 years showed better results than the adults, in posttraumatics the results seemed to be better in the adults. Mere mobilisation in anesthesia showed disappointing results in both groups generally. PMID- 8212810 TI - [Melorheostosis of the hand (report of 2 cases)]. AB - Melorheostosis is a rare monostotic or polyostotic bone disease of unknown etiology. It is characterized by a slowly progressing linear hyperostosis, fibrosis of the skin and subcutaneous tissues, contractures of joints and aching pain. The lower extremities are involved much more often than the upper extremities. The distribution of the lesion usually follows sclerotomes. Bone scanning complements standard radiologic studies and permits evaluation of the extent and activity of the disease. Here we report two cases of melorheostosis. Conservative treatment was disappointing. Thus we recommend the excision of the exostosis. PMID- 8212811 TI - [Results with Garth's modified roentgen exposures]. AB - With the apical oblique view of Garth, a modified ap-projection of the shoulder, the postero-lateral aspect of the humeral head (Hill-Sachs defect) and the antero inferior glenoidal rim (Bankart lesion) are well demonstrated. Additionally a posterior dislocation of the shoulder can be detected and an orthograde view of the glenohumeral joint can be obtained at the same time. The affected arm is kept close to the body which is advantageous in case of a fresh trauma. The apical oblique view has worked well at the radiological follow-up of 56 patients 10-23 years after the Eden-Hybbinette-Lange operation for chronic shoulder instability for an assessment of a Hill-Sachs lesion and of the fate of the bone block antero inferiorly. The results are described. Disadvantages of the apical oblique view are a geometrical distortion and an exposure to radiation which is three times that of a standard ap x-ray picture. PMID- 8212812 TI - [The use of ultrasonography in peroneal paralysis]. AB - We report the importance of ultrasound in 5 cases of neuropathies caused by popliteal compression of the peroneal nerve. The ultrasound is helpful for the indication of operative decompression. The ultrasound is a proper diagnostic method if sciatica could not be excluded. Unfortunately, not every compression can be evaluated by this method alone. PMID- 8212813 TI - [Muscle function of the thigh 10 years following a malignant bone tumor and implantation of a tumor prosthesis in the knee]. AB - To objectify the muscle function of 5 patients ten years after implantation of a tumor endoprosthesis of the knee simultaneous muscle force and IEMG was recorded. The muscular activity in the operated leg was found to be reduced for the extension muscles (8-20%) and for the flexion muscles (28-52%) when comparing to the normal leg. Knee extension of the operated leg resulted from the function of the rectus femoris muscle. During normal exercise in daily life all patients were not handicapped und some of them did sport. PMID- 8212814 TI - [Results of extensive cervical laminectomy]. AB - 39 patients were studied for late effects of cervical laminectomy. With a mean follow-up of 51 months and mean extent of laminectomy of 4.15 levels, analysis of pre- and postoperative radiographs showed changes in cervical spine curvature type in 72% and in 44% extreme spinal deformity. In addition, postoperative effects on pain and neurological symptoms are evaluated. Close follow-up during rehabilitation in essential for the prevention of clinical deterioration after laminectomy. PMID- 8212815 TI - [ligament kinematics of the ankle joint. An experimental study]. AB - In an experimental study using osteo-ligamentous preparations of ankle joints we studied the ligamentous kinematics of isolated ligament fibers of different lateral and medial ankle ligaments. Results demonstrate a different kinematic pattern of the ligaments depending on the joint position. The anterior fibula talar ligament shows an anisometric characteristic of different fibers and demonstrates a maximal ligament strain of the most anterior fiber in maximal plantarflexion; fibers located more dorsally have their maximal strain in plantarflexion of less degrees. In contrast to that the fibula-calcaneus ligament demonstrates a more isometric characteristic. At the medial side the different parts of the deltoid ligament also demonstrate a different kinematic characteristic. In contrast to the pars tibio-calcanearis which has a more isometric ligament kinematic of isolated fibers, ligament fibers of the pars tibiotalaris posterior demonstrate an anisometric ligament kinematic. For clinical aspects an anatomically correct reconstruction of ruptured ligaments and fractures as well as an anatomic reconstruction in chronic unstable ankle joints is recommended. PMID- 8212816 TI - [Standardized infection model for the study of bony ingrowth dynamics of hydroxyapatite-coated and uncoated pure titanium mesh in swine femur]. AB - The authors studied the ingrowth dynamics of bone tissue into the pores of Hydroxyapatite-coated (plasma-spraying technique) and uncoated wiremeshs of pure titanium in an infected implantation site. Samples of the tested materials were implanted into the femora of 15 adult Gottingen minipigs. Just before implantation they were contaminated with Staphylococcus aureus. The animals were sacrificed after 4, 8, 12 and 24 weeks. Undecalcified ground-sections of bone tissue were prepared (app. 100 microns) and stained with toluidine blue for comparative histological evaluation. The HA-coated implants demonstrated advanced new bone formation already after 4 weeks and nearly complete osseointegration after 12 weeks although all samples showed gross and histological signs of persisting infection. Comparable reactions of the uncoated implants could only be observed after 24 weeks. Signs of degradation of the Hydroxyapatite-coating could be seen in contact to soft tissue and were more extensive compared to the behaviour in an uninfected site. The results and possible clinical consequences are discussed. PMID- 8212817 TI - [Initial stability of an implanted cement-canal prosthesis. Results in experimental studies on human cadaver femurs]. AB - Upon implantation of a cement-canal prosthesis in the proximal femur in total hip replacement, the bone cement is injected through the prosthesis via a system of drill holes. A second system of drill holes is used in this endoprosthesis to drain the distal femoral space as well as the cavities within the cement layer which form when the cement is being injected. Since the cement pressure is sustained until the cement has cured, substantial penetration of the cement into the cancellous bone can be achieved by using low intra-medullary cement pressures. Using cadaveric human femurs, the initial stability in the trabecular intertrochanteric region was determined in pull-out experiments for three different curing cement pressures (0.5 bar, 1.0 bar and 1.5 bar). The results were compared to corresponding controls in which a conventional cementation technique was used. With respect to the contact area of the bone/bone-cement interface, the initial stability increased by the factor 2.8 (cement-curing pressure 0.5 bar), 3.7 (cement-curing pressure 1.0 bar) and 2.9 (cement-curing pressure 1.5 bar) compared to the control group. PMID- 8212818 TI - Characterization of the serum antibody response induced by Haemophilus influenzae type b tetanus protein-conjugate vaccine in infants receiving a DTP-combined vaccine from 2 months of age. AB - The serum antibody response induced by Haemophilus influenzae type b capsular polysaccharide (CPS)-tetanus protein conjugate vaccine combined to DTP vaccine was characterized in infants receiving three injections from 2 months of age. Sixty-five per cent and 94% of infants had anti-CPS antibody levels > or = 1 micrograms ml-1 after the second and third dose, respectively. The antibody response was mostly made up of IgG with a marked IgG1 predominance. Significant rises in bactericidal and in complement-mediated opsonic activities were observed after immunization. These data clearly show that this vaccine can be successfully administered in one syringe together with DTP vaccine during the regular infant immunization programme. PMID- 8212819 TI - Evaluation of different immunization schedules for oral cholera B subunit-whole cell vaccine in Swedish volunteers. AB - Different immunization schedules for oral B subunit-whole cell (B-WC) cholera vaccine were evaluated in Swedish volunteers to obtain information for recommendations of vaccine use in non-endemic areas. Two peroral doses of B-WC vaccine were as effective as three doses in inducing IgA and IgG antitoxin as well as vibriocidal antibody responses in serum. Administration of two vaccine doses either at 7, 14 or 28-42 day intervals resulted in comparable antitoxin responses in serum, whereas a 3-day immunization interval resulted in significantly lower titre increases. Vibriocidal antibody responses were comparable after the different time intervals tested (3-42 days). The B-WC vaccine can be effectively administered together with a cheap, commercially available sodium bicarbonate powder dissolved in water to protect the vaccine from gastric acid. PMID- 8212820 TI - Vaccination-induced HI antibody to influenza A(H1N1) viruses in poorly primed adults under circumstances of low antigenic drift. AB - In Autumn 1990, trivalent split influenza virus vaccine containing A/Taiwan/1/86(H1N1) was used to immunize healthy female employees (n = 104). The 11-12 amino acid differences in the HA1 domain of virus haemagglutinin between A/Taiwan/1/86 and representative epidemic H1N1 strains in Finland in 1991 did not result in lowered haemagglutination-inhibiting (HI) antibody responses to the latter viruses. In fact, higher prevaccination, postvaccination and postepidemic antibody titres were recorded against the new field strains than against the vaccine virus; the highest being against field strains grown exclusively in MDCK cell cultures. This pattern is primarily explained by differences in the sensitivity of the viruses for detecting HI antibodies. Postvaccination protection rates of 98-100% for the MDCK-grown avid viruses were noted in subjects who exhibited prevaccination antibody. Lower protection rates were recorded in initially seronegative subjects, the lowest (54-57%) being among older people, i.e. among vaccines born in 1930-1955 (p < 0.001). Moreover, conspicuous decreases in protection rates were detected during the following epidemic season in the initially seronegative subjects. Diagnostic findings during outbreaks due to H1N1 subtype viruses also support the impression that many middle-aged people are poorly primed. Thus, vaccination with two doses may be worth considering when such people join the high-risk group and receive influenza vaccine for the first time. PMID- 8212821 TI - Adhesion-mediated enhancement of the adjuvant activity of alum. AB - Alum, the only adjuvant currently licensed for use in humans, fails to adsorb influenza virus haemagglutinin (BHA) and is a poor adjuvant for this antigen. A specific monoclonal anti-BHA antibody adsorbed to alum promoted adhesion of the antigen to the adjuvant. The 'alum-anti-BHA-BHA' complex was found to be 1500 fold more immunogenic in mice and 5-fold more immunogenic in rabbits than a mixture of alum and BHA lacking the anti-BHA antibody. The biotin-binding protein, avidin, also mediated adsorption of biotinylated BHA to alum, and enhanced its immunogenicity to a comparable extent. These results indicate that the adjuvant activity of alum can be markedly enhanced by promoting a physical association between the antigen and the adjuvant. PMID- 8212822 TI - Simultaneous active and passive immunization against hepatitis A studied in a population of travellers. AB - Three hundred travellers, seronegative for hepatitis A, were enrolled into this study to evaluate a new inactivated hepatitis A vaccine. Three injections, each containing at least 720 ELISA units, were administered intramuscularly at months 0, 1 and 6. The subjects were distributed into three groups: 100 received vaccine only; 100 received a single injection of immunoglobulin enriched in HAV antibody; and the 100 remaining travellers received the vaccine and immunoglobulin administered simultaneously with the first vaccine dose. In both vaccinated groups, the rate of seroconversion was found to be higher than 90% at month 1, reaching 100% and 97.8% at month 2 in groups 1 and 3, respectively, and 100% at month 7. In the group receiving both vaccine and immunoglobulin, antibody production was somewhat slower and the final titres were, on average, slightly lower than those obtained in the group with the vaccine alone (GMT 2488 and 3614 mIU ml-1 respectively; p = 0.02). The vaccine appeared to be highly immunogenic in all subjects and was also well tolerated. The slight inhibition of antibody production, induced by the concurrent administration of immunoglobulin, does not affect the overall protection afforded by the vaccine. We conclude that simultaneous active and passive hepatitis A immunizations can be recommended. PMID- 8212823 TI - A 7-year follow-up of newborns vaccinated against hepatitis B. AB - Of 79 children born to asymptomatic HBsAg chronic carrier mothers and vaccinated at birth against hepatitis B, a total of 71, 66 and 56 could be serologically assessed after 1, 5 and 7 years, respectively. Anti-HBs titres (geometric means) of responders decreased from 2475 to 143 IU l-1 between 1 and 5 years of age and dropped to 82 IU l-1 by 7 years. At this time, a booster dose given to 34 children who showed anti-HBs titres lower or slightly higher than 100 IU l-1 significantly increased titres from 34 to 2985 IU l-1 (p < 0.001). Children whose titres following perinatal vaccination reached 100 to 1000 IU l-1 or above 1000 IU l-1 maintained protective levels (> 10 IU l-1) for 3 and 5 years, respectively. As in adults, anti-HBs titres recorded after the initial vaccination indicate the time at which infants should receive booster vaccination. PMID- 8212824 TI - Infection-permissive immunization with influenza virus neuraminidase prevents weight loss in infected mice. AB - In studies of infection of young Balb/c mice with a mouse virulent strain of X-31 (H3N2) influenza A virus we have shown a profound virus dose-related effect of infection on body weight. Most of this effect is prevented by prior administration of either inactivated whole virus vaccine, which prevents infection, or purified influenza virus neuraminidase, which is infection permissive, but reduces pulmonary virus replication by 1.5 to 3 orders of magnitude. These studies support the concept of infection-permissive immunization and suggest that levels of virus replication previously shown to be antigenic can be sustained without significant systemic effects. PMID- 8212825 TI - Vaccination with a heterologous respiratory syncytial virus chimeric FG glycoprotein demonstrates significant subgroup cross-reactivity. AB - A subunit vaccine candidate, termed FG, is a chimeric glycoprotein composed of the extracellular domains of the fusion (F) glycoprotein and the attachment (G) glycoproteins of a subgroup A respiratory syncytial virus (RSV). Two subgroups, A and B, of RSV differ primarily within the G glycoprotein. Therefore, it has been suggested that a subunit vaccine composed of the G glycoprotein would need to contain the G glycoproteins from both RSV subgroups. We have engineered a second chimeric glycoprotein, FGB, which is composed of the F glycoprotein from RSV subgroup A and the G glycoprotein from RSV subgroup B and is expressed in baculovirus. A comparison of protection between the two subunit vaccines (FG and FGB) was performed in cotton rats after homologous and heterologous virus challenge. FG and FGB appeared to afford the same degree of protection against either homologous or heterologous challenge. Serum neutralization titres against homologous or heterologous virus were nearly equivalent following FG or FGB vaccination. Radioimmunoprecipitation using sera from rats immunized with FG or FGB revealed cross-reactivity between the two G glycoproteins. Adsorption of anti F antibody from serum of rats immunized with FG significantly reduced the RSV neutralizing activity of the serum suggesting that enhanced neutralization previously observed with FG antisera compared with F antisera alone may not be entirely attributed to antibodies against the G glycoprotein but may be attributed to a function associated with the G glycoprotein portion of FG which enhances the immunogenicity of the F portion of FG. PMID- 8212827 TI - Antibody response to whole-virus and split-virus influenza vaccines in successful ageing. AB - The antibody response to influenza vaccination has been variably reported to be decreased in elderly individuals. To determine the effect of ageing alone on this antibody response, a group of carefully-screened healthy elderly subjects were compared with young adult controls. Antibody titres for several strains of influenza were measured before and after vaccination with whole-virus (WVV) and split-virus influenza vaccines (SVV) in two successive years. In general, the antibody response to WVV was greater than the response to SVV. Both groups showed a similar response to the H3N2 strain but the elderly group showed a lower response to the H1N1 and B strains of virus contained in the vaccine. Antibodies to older strains of influenza A but not B were stimulated by vaccination with SVV. In the elderly group, the response to older viral strains was relatively increased compared with newer strains. In contrast, the young control group had better antibody responses to the newer than to the older strains of influenza tested. Reductions in the antibody response to influenza vaccination may, therefore, be related to the phenomenon of original antigenic sin and the cohort effect of exposure to H1N1 during childhood in the elderly group studied. The increased immunogenicity of WVV must be considered in light of the current wide use of SVV in the elderly. PMID- 8212826 TI - Immune sera to individual Borrelia burgdorferi isolates or recombinant OspA thereof protect SCID mice against infection with homologous strains but only partially or not at all against those of different OspA/OspB genotype. AB - The outer surface proteins OspA and OspB of Borrelia burgdorferi have recently been demonstrated to be major target proteins for protective antibodies in mice against infection with the homologous spirochaetal strain. However, it has become clear from a variety of studies that B. burgdorferi isolates of different geographical origin and/or sources are heterogeneous and that they can be divided into at least six subgroups according to their distinct OspA/OspB genotypes. In order to analyse cross-protection between these subgroups we have now generated immune sera to various isolates of B. burgdorferi with different OspA/OspB genotypes. We show that passive immunization with antisera specific for whole spirochaetes or recombinant OspA of one spirochaetal isolate protects severe combined immunodeficiency mice against infection with strains of the corresponding OspA/OspB genotype but only partially or not at all against infection with isolates expressing distinct OspA/OspB genotypes. The incomplete protection mediated by individual antisera against independent isolates of B. burgdorferi suggests that an effective subunit vaccine against Lyme disease should consist of a mixture of OspA structures covering the heterogeneity of this protein within the species B. burgdorferi. PMID- 8212829 TI - Immunization of chickens with live Newcastle disease vaccine adjuvanted with oil. AB - Chickens of various ages and breeds were vaccinated subcutaneously with Newcastle disease live-in-oil vaccines. These vaccines were prepared immediately prior to the vaccination by mixing the lyophilized live vaccine with the oil adjuvant, which was kept at room temperature. The live-in-oil vaccines were shown to be 30 50 times more effective in efficacy tests than either the same vaccines reconstituted in water or killed-in-oil vaccines. In addition to its biological advantage, the method of preparation of live-in-oil vaccine saves the expensive space of cold storage and shipment necessary for conventional killed-in-oil vaccines. PMID- 8212828 TI - Cloning and DNA sequence of a 29 kilodalton polypeptide gene of Mycoplasma gallisepticum as a possible protective antigen. AB - A lambda gt11 clone, designated M1 and having a 0.8 kilobase (kb) insert, was selected by screening a Mycoplasma gallisepticum (M.g.) genomic DNA library with antisera against M.g. cells and their membrane proteins. The sequence of a 1.7 kb EcoRI fragment of genomic DNA covering the entire M1 insert revealed a long open reading frame, TM-1, that encoded a polypeptide with a deduced molecular weight of 29 kDa. An antiserum raised in chicken against the TM-1 polypeptide, which was produced by recombinant Escherichia coli cells and purified by column chromatography, inhibited growth of M.g. cells in vitro. Moreover, chickens immunized with this polypeptide were partially protected from a challenge with virulent M.g. This polypeptide may serve as the basis for a vaccine against M.g. infection. PMID- 8212830 TI - Anti-HBs and immunological memory to HBV vaccine: implication for booster timing. PMID- 8212831 TI - Efficacy of equine influenza vaccines for protection against A/Equine/Jilin/89 (H3N8)--a new equine influenza virus. AB - A new H3N8 equine influenza virus [A/Equine/Jilin/1/89 (Eq/Jilin)] appeared in Northeastern China in 1989 and caused high mortality in horses; the available evidence indicates that it has not yet spread outside this region of the world. Serological analysis with postinfection ferret sera in haemagglutination inhibition (HI) tests confirmed that Eq/Jilin is antigenically distinct from H3N8 equine influenza viruses isolated between 1963 and 1991 and also showed that a current equine influenza virus [A/Equine/Alaska/1/91 (H3N8)] had undergone antigenic drift. In the present study we determine if vaccine against a recent H3N8 influenza virus [A/Equine/Kentucky/1277/90 (Eq/Kentucky)] that was standardized for haemagglutinin content will protect mice against lethal challenge with the new H3N8 influenza virus from China. Complete protection is defined as prevention of virus replication in the lungs of mice 3 days after challenge. High doses of Eq/Kentucky vaccine in aqueous suspension (0.5-5.0 micrograms HA per dose) provided minimal protection against Eq/Jilin challenge as judged by virus titres in the lungs of vaccinated animals. Eq/Kentucky vaccine in adjuvant (1.0-5.0 micrograms HA per dose) did provide complete protection against challenge with Eq/Jilin in mice. Eq/Jilin vaccine in aqueous suspension induced complete protection of mice against challenge with Eq/Kentucky at doses from 0.5 to 5 micrograms HA and in adjuvant doses of Eq/Jilin from 0.1-5.0 micrograms HA were efficacious. Homologous protection against Eq/Jilin or Eq/Kentucky was induced by doses of vaccine from 0.5-5.0 micrograms HA per dose in aqueous suspension and from 0.01-5.0 micrograms HA per dose in adjuvant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212832 TI - The immunotargeting approach to adjuvant-independent immunization with influenza haemagglutinin. AB - By conjugating the bromelain fragment of the influenza virus haemagglutinin (BHA) to a mouse monoclonal antibody specific for a species-crossreactive, framework determinant on class II major histocompatibility complex molecules, the adjuvant independent immunotargeting approach could be compared with more conventional immunizations involving Freund's complete adjuvant (FCA) and alum, in different species. Both rabbits and ferrets made significant virus-blocking IgG responses to the immunotargeted BHA in the absence of adjuvant, and no adverse reactions were observed with the conjugate immunizations. As measured by enzyme-linked immunosorbent assay, these responses were equal to those observed with alum, and were approximately one-quarter of the level seen with FCA. In terms of influenza virus haemagglutination inhibition, immunotargeting appeared to be more effective than alum, but less effective than FCA. Collectively, the results indicate that immunotargeting may provide a safe and effective alternative to the use of adjuvants in the development of defined subunit vaccines. PMID- 8212833 TI - Vaccine therapy for HIV: a historical review of the treatment of infectious diseases by active specific immunization with microbe-derived antigens. AB - A review of the history of 'vaccine therapy' for infectious diseases is presented. The concept originated when Auzias-Turenne introduced 'syphilitic vaccination' or 'syphilization' as a treatment for syphilis in Paris in the mid 1800s; his clinical studies probably influenced Pasteur's successful rabies postexposure vaccine trials. Robert Koch in Berlin in the 1890s observed that inoculation of tuberculin into patients with tuberculosis induced an inflammatory response in affected tissues, and advocated 'tuberculin therapy'. Sir Almroth Wright in London in the early 20th century devised methods to measure changes in serum 'opsonizing' activity in response to therapeutic inoculations with microbe derived vaccines. Since the advent of antibiotics, active specific immunization with microbe-derived antigens (vaccine therapy) has been largely forgotten as a strategy for treatment of infectious diseases. Advances in antigen production and in molecular immunology now permit new tactics to probe, analyse and selectively alter in vivo human immune responses to infectious microbes. Our recent demonstration that vaccine therapy can boost natural immunity to HIV in infected patients should rekindle interest in this approach. PMID- 8212834 TI - Influenza vaccines: the effect of vaccine dose on antibody response in primed populations during the ongoing interpandemic period. A review of the literature. AB - Health authorities tend to favour an increase of the antigen dose in inactivated influenza vaccines from < or = 10 micrograms haemagglutinin (HA) per vaccine strain to 15 micrograms HA/strain. The increased dose is expected to yield a meaningful increase in the number of subjects to be protected after vaccination. To verify this expectation, we have reviewed 20 published reports (1978-1991) of serological studies in which anti-HA-IgG antibody after different doses was measured. In the review, stratification groups of previously primed subjects were formed and the antibody response was estimated for doses of 10 and 15 micrograms HA by linear k*2-chi 2 model. Despite a considerable heterogenicity of study populations, study designs, vaccine types and strains, and antibody assays, the results were consistent in revealing high protection rates (> or = 75%) for a 10 micrograms HA dose of influenza A vaccine components. For both response and protection rates, an increase of the antigenic load from 10 to 15 micrograms HA was not associated with a meaningful increase of seroresponse: in 38 out of 39 stratification groups, the increase of response and/or protection rate varied between -9% and +8%, with a median of 1.5%. These results do not justify the expectation that a vaccine dose of 15 micrograms HA per strain would be clinically superior to a dose of 10 micrograms HA. Only in a group of immune compromised patients on chronic intermittent haemodialysis were results in favour of a higher dose found, which may justify further evaluation in this special population. PMID- 8212835 TI - Pilot evaluation of influenza virus vaccine (IVV) combined with adjuvant. AB - The safety of licensed influenza virus vaccine (IVV) combined with a novel adjuvant containing muramyl tripeptide (MTP) conjugated to phosphatidylethanolamine (PE) was evaluated in a randomized pilot study. Ten healthy 23-30-year-old men were given a single intramuscular dose of IVV combined with saline (n = 5) or with 100 micrograms of MTP-PE in the MF59 adjuvant emulsion (MF59-100) (n = 5). Evaluations were performed on days 0, 1, 2, 4, 7 and 28 after inoculation. IVV alone was well tolerated. All volunteers immunized with IVV/MF59-100 experienced moderate to severe local and systemic reactions which interfered with usual activities. Discomfort at the injection site was first noted at 2-6 h; induration (5/5), erythema (3/5), and regional adenopathy (3/5) persisted for up to 4 days. Systemic symptoms including chills (5/5), fever (3/5), nausea (3/5) and/or dizziness (2/5) developed within 12 h of inoculation and resolved by 48 h. Elevated white blood cell count (days 1 and 2), erythrocyte sedimentation rate and serum fibrinogen were transiently observed. Although peak serum neutralizing antibody titres versus influenza A/H3N2 and influenza B antigens were higher in the group given IVV with MF59-100, these unexpected reactions indicate that this dose of adjuvant is unsuitable for use in combination with this IVV. PMID- 8212836 TI - Studies on the toxicities of aluminium hydroxide and calcium phosphate as immunological adjuvants for vaccines. AB - Aluminium hydroxide (Al) and calcium phosphate (Ca) have been used for many years as immunological adjuvants for biologicals. We investigated the toxic effects of both adjuvants with different physical properties. Al-gel elicited vascular permeability-increasing and toxic effects to macrophages (M phi), while its haemolytic effect was weak. Ca-gel elicited a significantly stronger haemolytic effect, but no other toxic effect. Incubation of M phi or polymorphonuclear leucocytes with Al-suspension resulted in the largest release of lactate dehydrogenase. Ca-suspension caused haemolysis of about 50% of that caused by Ca gel. PMID- 8212837 TI - Induction of T-cell immunity to oligosaccharide antigens immobilized on crystalline bacterial surface layers (S-layers). AB - Immunization of Balb/c mice with conjugates of oligosaccharide haptens and crystalline bacterial surface-layer proteins (S-layers) primed the mice for a strong, hapten-specific, delayed-type hypersensitivity (DTH) response. Conjugates of haptens with bovine serum albumin produced only weak DTH responses but, when mixed with aluminium hydroxide, elicited DTH responses comparable to those against S-layer conjugates. Surface-layer conjugates also elicited strong anti hapten DTH responses when administered by an oral/nasal route. Apparently, the natural assembly of S-layer proteins into large, two-dimensional arrays endows them with intrinsic adjuvant properties. PMID- 8212838 TI - Oral vaccination of racoons (Procyon lotor) with baculovirus-expressed rabies virus glycoprotein. AB - Successful field oral vaccination and protection against viral diseases have so far been achieved only with live-attenuated or live-recombinant virus vaccines. In this communication, we present data that demonstrate that a glycoprotein derived from recombinant baculovirus-infected insect cells is efficacious as an oral vaccine. The glycoprotein (G) of rabies virus (Evelyn Rokitnicki Abelseth strain) was abundantly expressed in a baculovirus expression system and oral vaccination of racoons with the baculovirus-expressed G protein resulted in the production of rabies virus-neutralizing antibodies and protection against a lethal challenge with a street rabies virus. The potential for using the baculovirus-expressed G protein for oral immunization of wildlife is discussed. PMID- 8212839 TI - Intestinal antibody response after oral immunization with a prototype cholera B subunit-colonization factor antigen enterotoxigenic Escherichia coli vaccine. AB - A prototype oral enterotoxigenic Escherichia coli (ETEC) vaccine containing formalin-inactivated whole bacteria expressing colonization factor antigens CFA/I and CFA/II and cholera B subunit (CTB) has been tested for safety and immunogenicity in 20 adult Swedish volunteers. When given in three doses with 2 week intervals the vaccine was found to be safe and to give rise to specific IgA antibody responses in intestinal lavage fluid in most of the volunteers (CFA/I 82%, CFA/II 82% and CTB 91%). The frequencies and magnitudes of these responses, which were already maximal after two doses, were comparable with those previously found in patients convalescing from severe ETEC diarrhoea. All the vaccinated volunteers also responded with antitoxin IgA as well as IgG antibodies in serum, whereas the serum antibody responses against the CFAs were weaker and mainly of the IgA isotype. PMID- 8212840 TI - Tetanus immunity among Italians born after the introduction of mandatory vaccination of children. AB - In Italy systematic mandatory tetanus immunization of children started in 1968. In a national sample of 241 young males born after 1968 the prevalence of non immune subjects was 11.2% (5.5% in the North-Centre, 15.9% in the South-Islands; p < 0.02). Comparing these data with the corresponding figure obtained in a previous study of subjects born before 1968 a significant decrease (11.2% versus 32.6%; p < 0.01) is observed. The prevalence of non-immune subjects born after 1968 is significantly (p < 0.01) lower than that observed in subjects born before 1968 by geographical area as well as by area (urban/rural) of residence. These findings indicate that the introduction of compulsory tetanus vaccination for all newborns has favourably affected the immune status of younger Italian men. However, more efforts should still be addressed to decrease regional inequalities in the delivery of health care. PMID- 8212841 TI - Antigenicity of a candidate varicella-zoster virus glycoprotein subunit vaccine. AB - A 1642 bp DNA fragment, encoding the N-terminal region and 511 amino acid residues of varicella-zoster virus (VZV) glI gene, was inserted into vaccinia virus genome. The expression of recombinant vaccinia virus (designated VVTgpI 511) yielded the synthesis of a 60 kDa protein species which was processed to a secretory 76 kDa polypeptide (designated TgpI-511). The antigenicity of this protein was examined by subcutaneous inoculation of one rabbit with 100 micrograms purified TgpI-511 in the Ribi adjuvant system. The animal was boosted 3 weeks after the initial inoculation and antisera were tested 7 days after the last injection by immunoprecipitation and neutralization tests. The results showed that rabbit antibodies to TgpI-511 (RAnti-TgpI-511) were reactive with purified TgpI-511 as well as native gpI in VZV-infected cells. In addition, TgpI 511 was capable of eliciting complement-dependent VZV neutralizing antibodies. These results suggested that the purified preparation of TgpI-511 may have the potential to be used as a candidate VZV subunit vaccine. PMID- 8212842 TI - Comparison of enhanced chemiluminescence and microparticle enzyme immunoassay for the measurement of hepatitis B surface antibody. AB - Two commercially available immunoassays for the quantitative measurement of antibodies to hepatitis B surface antigen (HBsAg) were compared. The Amerlite enhanced chemiluminescence assay (ECL), which utilizes capture antigen obtained from HBsAg-positive donors bound to microtitre wells, was compared with the Abbott Laboratories microparticle enzyme immunoassay (IMx), which uses a recombinant antigen coated on to microparticle carriers. A total of 310 specimens, 116 from naturally infected patients (group A), 93 from patients vaccinated with a human plasma-derived vaccine (group B) and 101 patients vaccinated with a recombinant vaccine (group C), were tested in both assays undiluted and diluted 1:11. Samples that showed discordant results were also tested in a conventional quantitative enzyme immunoassay (Sorin). The results show significant differences in the level of anti-HBsAg in patient sera using the two technologies. In general, IMx gave significantly higher values than ECL for all three patient categories tested. These differences may lead to conflicting reports being issued by laboratories who change their assay system or when a sample from one patient is tested by different laboratories using different assays. PMID- 8212843 TI - Protection against a lethal influenza virus challenge by immunization with a haemagglutinin-expressing plasmid DNA. AB - Direct DNA inoculations have been used to demonstrate that in vivo transfections can be used to elicit protective immune responses. The direct inoculation of an H7 haemagglutinin-expressing DNA protected chickens against lethal challenge with an H7N7 influenza virus. Three-week-old chickens were vaccinated by inoculating 100 micrograms of plasma DNA by each of three routes (intravenous, intraperitoneal and subcutaneous). One month later, chickens were boosted with 100 micrograms of DNA by each of the three routes. At 1-2 weeks postboost, chickens were challenged via the nares with 100 lethal doses of an H7N7 virus. Low to undetectable levels of H7-specific antibodies were present postvaccination and boost. High titres of H7-specific antibodies appeared within 1 week of challenge. In a series of four experiments, 50% (28/56) of the DNA-vaccinated and < 2% (1/67) of the control chickens survived the challenge. This exceptionally simple method of immunization holds high promise for the development of subunit vaccines. PMID- 8212844 TI - Protection of goats against peste des petits ruminants with a vaccinia virus double recombinant expressing the F and H genes of rinderpest virus. AB - Peste des petits ruminants (PPR) is a viral disease of goats and sheep characterized by necrotizing and erosive stomatitis, enteritis and pneumonia. The causative agent, PPRV, is a member of the family Paramyxoviridae and the genus Morbillivirus. Other members of the genus include rinderpest (RPV), measles, canine distemper and phocid distemper viruses. PPR has a very high rate of morbidity and mortality, and effective control of this disease is of economic importance in Africa, Asia and the Middle East. Currently, there is no safe and effective vaccine available against the disease. The tissue culture rinderpest vaccine (TCRV) protects small ruminants against severe disease; there are, however, clinical problems associated with vaccination. This laboratory has recently developed several effective vaccinia virus recombinant vaccines for rinderpest. These vaccines are easy to administer, inexpensive to produce and heat-stable. Goats were vaccinated with a vaccinia virus double recombinant expressing the haemagglutinin and fusion genes of RPV. Although vaccinated animals developed antibodies (neutralizing and ELISA) to RPV, and not to PPRV, they were completely protected against challenge inoculation with virulent PPRV. This would indicate that protection is most probably due to cell-mediated immunity. Use of the rinderpest double recombinant vaccinia virus in areas of the world where PPRV is endemic would aid in the control and eradication of PPR. PMID- 8212845 TI - Long-term antibody responses in mice following subcutaneous immunization with ovalbumin entrapped in biodegradable microparticles. AB - Ovalbumin (OVA) was entrapped in microparticles prepared from three different poly(lactide-co-glycolide) (PLG) polymers and the microparticles were administered subcutaneously to mice as a single dose. Two weeks after immunization, the serum IgG antibody response to OVA entrapped in microparticles was significantly greater than the response to soluble OVA. The response to OVA entrapped in microparticles peaked at week 10 and remained high for the full 1 year duration of the study. In a second study, the effect of particle size on the immunogenicity of PLG microparticles with entrapped OVA was assessed. Following booster immunizations in mice, microparticles of 1.5 microns were significantly more immunogenic than microparticles of 72.6 microns. Furthermore, although enhanced serum IgG responses were induced by immunization with OVA adsorbed to microparticles (1.0 microns), entrapment of the OVA in microparticles (1.5 microns) resulted in significantly better responses. PMID- 8212846 TI - Assessment of non-protein impurities in potential vaccine proteins produced by Bacillus subtilis. AB - The levels of non-protein impurities at different stages of purification of model vaccine proteins produced by Bacillus subtilis were assessed with special emphasis on peptidoglycan-wall teichoic acid and lipoteichoic acid. Intracytoplasmically produced proteins were purified by disrupting the lysozyme protoplasts using osmotic shock, depositing the inclusion bodies by low-speed centrifugation, and washing them with detergent. By this procedure most of the cell envelope-derived impurities could be removed. The final product contained less than 1% (w/w) of neutral sugars, fatty acids, phosphate, hexosamine, diaminopimelic acid and glycerol. A secreted protein was purified from the culture supernatant by successive ion-exchange and adsorption chromatography. The cell envelope-derived impurities were efficiently removed by the cation exchanger, and the final product contained only minute amounts of non-protein components. The amounts of non-protein components such as peptidoglycan and lipoteichoic acid in proteins produced in either mode were shown to be negligible in relation to their potentially harmful biological effects. PMID- 8212848 TI - Human leucocyte antigens (HLA) in neonates with an inadequate response to hepatitis B vaccination. PMID- 8212847 TI - Anti-polyribosyl-ribitol phosphate and anti-N. meningitidis outer membrane protein antibody levels following PRP-OMP conjugate vaccination. PMID- 8212849 TI - A persistent infection in MDCK cells by an influenza type B virus. AB - A persistent infection in Madin Darby Canine Kidney (MDCK) cells by an influenza B virus (B/Tecumseh/63/80) has been established and characterized. Virus recovered from the persistent state titrated lower in relation to the parental wild-type (wt) that initiated the infection as measured by hemagglutination and egg and tissue culture infectious dose, suggesting that the virus is a less cytopathic variant of the original wt virus. The persistent virus (pv) has decreased cytopathology for both MDCK and primary chick kidney (PCK) cell lines, and exhibits different RNA and protein electrophoretic migrations. Plaques of the persistent virus are smaller and take longer to appear, indicating that the pv is a slower growing variant of the wt. The small plaque mutant phenotype may play a role in the maintenance of the persistent infection in MDCK cells. The pv differs from the wt antigenically and in its ability to form deposits of uric acid-like crystals beneath the culture monolayers. PMID- 8212850 TI - The evolution of virus diseases: their emergence, epidemicity, and control. AB - The evolution of virus diseases, both their emergence and disappearance, involves complex interactions between the agent, the host, and the environment. These themes are illustrated by three examples, poliomyelitis of humans, bovine spongiform encephalopathy of cattle, and AIDS of humans. Emergence may be due to evolution of the virus genome, such as probably occurred in parvovirus infection of dogs and human immunodeficiency virus infection of humans. However, emergence of some new viral diseases can be traced to host or environmental factors with no change in the agent. Poliomyelitis, an enteric infection, probably emerged as an epidemic disease due to improvements in personal hygiene and public sanitation which led to a delay in the occurrence of initial infections from the perinatal period (when maternal antibody protected against paralysis) to later childhood when passive immunity had waned. Bovine spongiform encephalopathy is a common source epidemic which was transmitted through nutritional supplements which became contaminated due to a change in the method of production of bone meal supplements in rendering plants. The reduction of disappearance of virus diseases usually involves human intervention, as exemplified by immunization for smallpox and other virus diseases of humans and animals. Naturally occurring immunity may lead to fadeout of a virus as seen with measles in isolated island populations. Evolution of a virus can also result in waning of a disease as seen with myxomatosis among rabbits in Australia. The evolution of virus diseases is a provocative scientific topic and carries lessons relevant to the control of important diseases of humans, animals, and plants. PMID- 8212851 TI - Association of '(tropical) ataxic neuropathy' with HTLV-II. AB - Jamaican Neuropathy of the ataxic type (tropical ataxic neuropathy [TAN] and spastic type (tropical spastic paraparesis [TSP]) have been recognized for over a century in Jamaica. The recent association of TSP with HTLV-I (TSP/HAM) is now well established. We now present evidence for a possible association between a TAN-like illness with HTLV-II in four females aged 34-49. All presented with ataxic gait and all four have prominent mental changes. Three of the four also have minor motor deficits with urinary frequency and two have nocturnal leg cramps. All have serum antibody and all had PCR evidence of HTLV-II infection. Antibody to HTLV-II is present in CSF from two subjects. The distinctive picture of prominent ataxia and altered mental status in these subjects contrasts with a predominantly myelopathic picture seen in TSP/HAM. PMID- 8212852 TI - Human herpesvirus 6 (HHV-6)-associated dysfunction of blood monocytes. AB - HHV-6 is a recently described member of the herpesvirus family. HHV-6-associated marrow failure and interstitial pneumonitis where macrophages are the primary infected cell type have been described in marrow transplant patients (Carrigan, 1991; Drobyski et al., 1993). In recent studies we have shown that exposure of normal human marrow to HHV-6GS (a type A strain) or several type B strains resulted in suppression of growth factor induced outgrowth of macrophages by > 90% (Burd and Carrigan, 1993). Additional experiments using HHV-6GS to characterize the effects of the virus on peripheral blood monocytes showed that the respiratory burst capacity of these cells as determined by luminol-enhanced chemiluminescence using phorbol myristate acetate as a trigger was decreased by 83% +/- 13% in a series of 5 experiments. The decreased respiratory burst was evident as early as 15 min after exposure to virus. Experiments in which cells were separated on a fluorescence activated cell sorter prior to respiratory burst assay showed that the response was mediated solely by peripheral blood monocytes. The respiratory burst response of virus-exposed cells to opsonized zymosan was not affected, indicating that the virus may selectively interfere with the protein kinase C pathway of cellular activation. Ultracentrifugation of stock material to remove infectious virus showed that the suppressive factor was associated with the supernatant fraction. These findings suggest that HHV-6 infection may be associated with a defect in one of the major monocyte activation pathways, and this could be of importance with respect to persistent infection by HHV-6 in immune compromised patients. PMID- 8212853 TI - Frequent isolation of human herpesvirus 7 from saliva. AB - We obtained isolates of human herpesvirus 7 (HHV-7) from 6 of 8 healthy adults by culturing saliva with human umbilical cord blood lymphocytes. These isolates were identified as HHV-7 on the basis of comparisons of restriction endonuclease fragment profiles and hybridization with HHV-7 strain RK DNA. The isolates could be differentiated from HHV-7 strain RK and from each other by their restriction endonuclease fragment profiles. We confirm the finding of frequent isolation of HHV-7 from saliva of healthy adults and report the first dual isolation of human herpesvirus 6 (HHV-6) and HHV-7 from a single saliva specimen. We also describe an in situ hybridization assay that can distinguish between HHV-6 and HHV-7. PMID- 8212854 TI - Possible relation between the U54 segment of the CTHV genome and the conserved gene block C rearranged in alpha and gamma herpesvirus genomes. AB - The genome of CTHV is an atypical member of the gamma-2 subgroup of herpesvirus genomes that contains two segments (instead of one) of DNA with low G+C content flanked by highly repetitious DNA with high G+C content. The segments freely undergo polarity inversion with respect to one another. We have found nucleotide sequences in one of these segments, the U54 segment, whose putative translational products show clear similarity to two ubiquitous herpesvirus gene products, a single-stranded DNA binding protein and a protein of the helicase superfamily. These sequences are located within 5 kilobase pairs of the ends of the segment, suggesting that U54 may be related to a genetically defined entity (gene block C; Davison and Taylor (1987) J. Gen Virol. 68, 36-48) issuing from a previous sequence comparison of the gamma-1 genome of Epstein-Barr virus and the alpha genome of varicella-zoster virus. PMID- 8212855 TI - Identification of an infectious laryngotracheitis virus gene encoding an immunogenic protein with a predicted M(r) of 32 kilodaltons. AB - The nucleotide sequence of an infectious laryngotracheitis virus (ILTV) gene which maps immediately upstream from the glycoprotein 60 (gp60) gene was determined. The gene, designated p32, encodes a predicted polypeptide of 298 amino acids with an estimated M(r) of 32,000 daltons. The predicted protein sequence has four potential N-glycosylation sites and a signal sequence at the N terminal region. Amino acid residues in the NH2-terminal region of the p32 protein exhibit similarity to glycoprotein X (gX) of pseudorabies virus (PRV) and its homolog in equine herpesvirus type 1 (EHV-1). Within the conserved (N terminus) region, one putative N-linked glycosylation site and four cysteine residues are aligned in these proteins. These common structural features of the gX-like proteins were also found in glycoprotein G (gG) of human herpes simplex virus type 2 (HSV-2) and equine herpesvirus type 4 (EHV-4). High level bacterial production of the p32 protein was achieved by cloning the p32 open reading frame into a pGEX-2T expression vector. Western blot analysis of the fusion protein produced in E. coli using immune chicken sera confirms that p32 protein is of viral origin and is an immunogen in birds with infectious laryngotracheitis (ILT). An antiserum from chicken immunized with the fusion protein detected a substantial amount of p32 protein in the medium of ILTV-infected cells in Western blotting. Moreover tunicamycin treatment of cells infected with the virus indicated that p32 was glycosylated. This allows us to conclude that p32 is a glycoprotein and like gX of PRV accumulates in the medium of infected cells. PMID- 8212856 TI - Alterations of the stalk of the influenza virus neuraminidase: deletions and insertions. AB - The neuraminidase (NA) of influenza viruses cleaves sialic acids from receptors, prevents self-aggregation and facilitates release of virus during budding from host cells. Although the structure and function of the globular head of the influenza virus NA has been well studied, much less is known about the stalk of the NA, the region between the viral membrane and the globular head. Applying a reverse genetics system, we altered the stalk of the influenza A/WSN/33 virus NA by making deletions, insertions and mutations in this region of the gene. Our data show that the length of the NA stalk can be variable. Deletions of up to 28 amino acids and insertions of up to 41 amino acids in the stalk region did not abolish formation of infectious progeny virus. The data also indicate that the cysteine at position 76 is essential for formation of infectious virus, and that deletions beyond the cysteine did not result in infectious virus. Interestingly, shortening of the length of the stalk region by 28 amino acids resulted in a virus with a markedly reduced growth rate in MDCK cells as compared to that in MDBK cells. An insertion of 41 extra amino acids into the stalk did not significantly interfere with viral growth in MDCK or MDBK cells, which suggests that the stalk region would tolerate the introduction of long foreign sequences. PMID- 8212857 TI - Influenza virus strains selectively recognize sialyloligosaccharides on human respiratory epithelium; the role of the host cell in selection of hemagglutinin receptor specificity. AB - The complement of sialyloligosaccharides present on the surface of human tracheal epithelium has been implicated as an important factor in the selection of hemagglutinin receptor specificity of human influenza A virus. Human strains of influenza A virus preferentially recognize host cell receptors bearing SA alpha 2,6Gal sequences, a sequence which is found on the surface of ciliated tracheal epithelium. A fluorescently-labelled H3 human virus strain bound avidly to the apical surface of human tracheal epithelium, while a fluorescently-labelled receptor variant strain, which preferentially binds SA alpha 2,3Gal sequences, showed little binding to the epithelial surface and localized primarily to intracellular mucin droplets. Extracts of human bronchial mucin, which is known to contain sialic acid primarily in the SA alpha 2,3Gal linkage, was a potent inhibitor of the binding of the receptor variant strain to trachea sections, while the binding of the parent strain was unaffected by the presence of mucin. Human bronchial mucin also inhibited the binding of the receptor variant strains, but not the parent virus strains, to human erythrocytes derivatized to contain SA alpha 2,6Gal sequences. These results suggest that a combination of selection pressures present in the respiratory tract environment have resulted in the evolution of a hemagglutinin receptor specificity in human influenza A virus strains which optimizes recognition of, binding to and infection of host cells. PMID- 8212858 TI - The HSV-1 UL45 18 kDa gene product is a true late protein and a component of the virion. AB - Previously we constructed a null mutation in the HSV-1 UL45 gene, showed that the UL45 gene was not required for growth in Vero cells, and confirmed that it coded for an 18 kDa protein (R.J. Visalli and C.R. Brandt, Virology 185:419-423, 1991). In this study, we have continued our characterization of the UL45 gene and the 18 kDa protein. Analysis of UL45 RNA revealed that the gene was expressed late and was inhibited in the presence of phosphonoacetic acid (paa), indicating it is a gamma 2 class gene. Using a specific polyclonal antiserum, we found that the 18 kDa UL45 gene product was also expressed late and was inhibited in the presence of paa. The 18 kDa protein was present in purified virions and was substantially enriched in the envelope-tegument fraction of virions disrupted with NP-40 detergent. The 18 kDa protein is thus a structural protein of the virus and appears to be associated with the viral envelope. A 20 kDa protein that cross reacted with a polyclonal HSV-1 UL45 antiserum was also detected in cells infected with HSV-2 strain 333. PMID- 8212859 TI - Protection of three strains of mice against lethal influenza in vivo by defective interfering virus. AB - This report examines the protective effects of defective interfering (DI) WSN on three strains of mice (C3H/He-mg (H-2k), C57BL/6 (H-2b) and BALB/c (H-2d)) infected with various doses of A/WSN influenza virus. All three strains were protected in terms of morbidity and mortality, to varying extents, DI WSN protected optimally against a low but lethal dose of A/WSN in C3H/He-mg mice, but also protected this and other strains against very high doses of A/WSN. Intermediate sized inocula gave little, if any, protection. In all cases protection required an active DI genome since inactivation with beta propiolactone abrogated any sparing effect. Consolidation of the lungs was reduced by treatment with active DI virus, but at some doses of inoculum there was reduction in lung pathology without reduction of mortality. Treatment of infected mice with DI virus did not reduce the lung virus titre, but in C3H/He-mg mice resulted in recovery of infectious virus from other tissues, notably the heart, where it was not normally found. No infectivity was recovered from brain, liver or serum. Haemagglutination-inhibiting (HI) antibody could not be detected in the lungs of any of the infected mice co-inoculated with the control BPL inactivated DI WSN but was present in considerable amounts in all three strains when these were co-inoculated with DI virus. These and previous data (Morgan and Dimmock, 1992) suggested that influenza virus was immunosuppressive and that active DI virus abrogated these suppressive effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212860 TI - Structure and sequence comparison of bovine respiratory syncytial virus fusion protein. AB - The fusion (F) proteins of 10 strains of bovine respiratory syncytial virus (BRSV) were compared by radioimmunoprecipitation with fractionation on SDS polyacrylamide gels. Two different molecular weights (15 kDa and 20 kDa) of the F2 proteins were demonstrated among the BRSV strains tested. To delineate the molecular basis for differences in the molecular weights of F2 subunits among the BRSV strains, the nucleotide sequences of the F genes of FS1 and VC464 strains were determined from cDNA clones. The deduced amino acid sequences were then compared to those of BRSV strains RB94, 391-2 and A51908. The F gene was highly conserved (> 95%) among BRSV strains. Comparison of the deduced F2 amino acid sequences showed that the strain with F2 subunits of 20 kDa had three N-linked glycosylation sites, whereas the strains with F2 subunits of 15 kDa had two N linked glycosylation sites. Analysis of F2 subunits in their deglycosylated forms indicated that the difference in the molecular weights of the F2 subunits was due to the difference in the extent of glycosylation. PMID- 8212861 TI - Replication cycle and associated biosynthetic reactions for a non-oncogenic avian adenovirus. AB - The replication cycle of the non-oncogenic fowl adenovirus serotype 10 (FAV-10) has been examined. The onset of viral DNA synthesis was shown to commence at about 10 h postinfection (hpi) defining the early period of viral replication as prior to this time and the late phase as that time following the initiation of DNA replication. Virus titre rapidly increased between 18 and 24 hpi with maximum virus yield between 28 and 30 hpi. The late phase transcription profiles of the FAV-10 genome from 10 hpi to 24 hpi were determined. Late translation of virus protein began about 14 hpi increasing rapidly between 18 and 30 hpi. PMID- 8212862 TI - A parvo-like virus persistently infecting a C6/36 clone of Aedes albopictus mosquito cell line and pathogenic for Aedes aegypti larvae. AB - We have isolated and partially characterized from an apparently healthy C6/36 subclone of Aedes albopictus cell line a small icosahedral non-enveloped DNA virus, designated AaPV. This virus proved to be highly pathogenic for Aedes aegypti neonate larvae. Viral infection persisted for over 4 years in the cell culture without any cytopathic effect. Attempts to infect suckling mice, Drosophila melanogaster adults and Spodoptera littoralis larvae with AaPV were unsuccessful. Similarly, the AaPV failed to replicate in vertebrate and Drosophila cell lines. Virions, about 22 nm in diameter, had a buoyant density of 1.43 g/cm3 and contained three capsid polypeptides with molecular weights of 53, 41 and 40 kDa. A preliminary study of the viral genome indicated the presence of single-stranded DNA. By its biophysical and biochemical properties, this virus appears to be related to the genus Densovirus within the family Parvoviridae, but lacks serological relationships with the other members of this genus. PMID- 8212863 TI - [Issue devoted to Vladimir Sergeevich Rusinov on occasion of his 90th birthday and 65 years of scientific work]. PMID- 8212864 TI - [Reciprocal inhibition in the dominant]. PMID- 8212865 TI - [The cortico-hypothalamic relations of the electrical activity in a motor polarization dominant]. AB - By means of spectral-correlation analysis was studied the dynamics of the structural changes of coherent relations of the electrical activity of the sensorimotor cortex and the medical hypothalamus (MH) of the rabbit under motor polarization dominant created by the action of DC anode on the sensorimotor cortex area. During the motor dominant the spectral power of MH activity was shown to increase in the delta-band. The structural changes of coherent relations of the electrical activity of the sensorimotor cortex and the MH were manifested by a decrease of coherence in the delta- and alpha-frequency bands. Electrical stimulation of the MH inhibited the motor dominant reactions. PMID- 8212866 TI - [A coherence analysis of the electrical activity of the rabbit brain in a thirst dominant]. AB - Study of the spatial-temporal relations of the brain electrical activity at the dominant of thirst revealed a definite reconstruction of electrical processes' interrelations in the cortex and subcortex in a low-frequency range. Regular increase of coherence level in the delta-range took place between the potentials of the frontal cortical area and APL, AHA, PV testifying to a formation of a primary dominant focus in these structures. At tonic state of the dominant the greatest increase of coherence function evaluations took place in the theta 1 range; before summation movement maximal values of coherence were observed in the theta 2-range. The above-mentioned differences are probably connected with the different levels of motivational-emotional excitation, appearing at corresponding stages of a dominant manifestation. PMID- 8212867 TI - [The restructuring of the intercentral relations of the electrical processes in the rabbit brain in a motor dominant]. AB - On rabbits in chronic experiments by the method of coherent analysis were studied intercentral relations of biopotentials of the sensorimotor cortex and VPL of the thalamus at formation of the motor dominant created by serial electrical stimulation of a leg. In the structures connected with the motor function of the stimulated leg was revealed an increase of coherence of the potentials in the delta-range. At transition of the dominant focus to the inhibitory state and activation of the symmetrical centre of the other leg, in the centers constellation of this induced focus a reconstruction of the electrical processes took place being typical for the dominant. It was shown that the different functional states of the motor dominant (the background, the tonic dominant state and the state before the summation motor reaction) were characterized by different parameters of mean coherence levels of electrical activity in the rabbit's brain. PMID- 8212868 TI - [A spectral-correlational analysis of the electrical activity of the rabbit brain during the extinction of an endogenous food conditioned reflex]. AB - Spectral analysis of electrical activity showed that at the end of extinction of the alimentary conditioned responses, elaborated on the basis of the hunger dominant, the spectral density of electrical activity of the cortical centre of the goal-directed reaction (blinking) of the trained eye and that of the lateral preoptic area, lateral hypothalamus, and ventromedial hypothalamus raised in the delta-band. To the end of the extinction the coherence (Cog) of biopotentials of the cortical centres of blinking of both eyes and electrical activity of the ventro-medial hypothalamus and medial preoptic area was changed in different directions. After the extinction of the goal-directed reaction Cog between biopotentials of the lateral hypothalamus and the electrical activity of the frontal cortex raised in the delta-band and Cog between the activity of the lateral hypothalamus and that of the cortical centres of blinking of both eyes lowered. The level of excitation of the structures included in the dominant constellation was suggested to raise to the end of the extinction of the endogenous conditioned response. PMID- 8212869 TI - [Spreading depression in the corticostriatal system of the rat brain during a seizure process induced by the daily administration of pentylenetetrazole]. AB - Spreading depression (SD) in the cortex and the caudate nucleus induced by 40 mg/kg i.p. pentylenetetrazole (PTZ) injection was studied in awake rats with implanted carbon electrodes. It was shown that spontaneous bilateral occurrence of cortical SD was the most probable and had an effective inhibitory influence on seizures after the first PTZ application. Penetration of cortical SD waves into the caudate nucleus and their return to the cortex substantially prolonged the anticonvulsive effects of SD. In the course of daily repeated PTZ injections the cortico-caudate SD propagation reduced progressively being accompanied by a decrease of efficiency of its inhibitory effect and interictal spike activity intensification. Similar restriction of SD propagation was observed without any seizure manifestations under the conditions of daily cortical electrical stimulation (without systemic drug treatment). So, reducing the cortico-caudate SD incidence during PTZ kindling is rather the cause of seizure facilitation than its consequence. PMID- 8212870 TI - [The modelling of the modes of propagation of SD waves in brain structures taking into account the nonuniform density of the active elements]. AB - Character of spreading depression (SD) wave propagation was studied on two dimensional model of excitable tissue. It was shown that strips with diminished density of active elements were of different permeability for the waves depending on their front orientation and curvature. When triggered near the border with a rarefied strip the wave could not penetrate through it and the effect of wave "sliding" along this strip was observed. In several-compartment model imitating the diffusely connected cortico-striatal system of the rat brain the sequence of events was determined by a primary focus position. In this model a single stimulus could provoke not only one wave but re-entry waves and reverberators. Described mechanism of repetitive waves generation in inhomogeneous tissue allow to interpret unusual SD wave consequences observed in electrophysiological experiments. PMID- 8212871 TI - [The hunger dominant in man and the reactions of the autonomic nervous system]. AB - Formation of hunger dominant takes place in man under the conditions of alimentary deprivation and application of sensory stimuli. Summation reactions, namely, swallowing movements, appear in response to the stimuli. Time of deprivation necessary for dominant formation is different in different subjects. Study of ECG, GSR, and respiration during the dominant formation revealed an increase of vegetative reactivity during application of the testing stimuli and before the summating swallow as well. The obtained data allow to make a conclusion on the active participation of the vegetative component in the formation of dominant constellation. The former joins the summation process earlier than the motor component. PMID- 8212872 TI - [The "midbrain waves" (MBW) in the human electroencephalogram]. AB - The dynamic EEG study was performed in 19 patients with mesencephalic damages (verified by the contrast methods and during the surgery). A new EEG phenomenon, mesencephalic waves (MW), was observed in the early postsurgery period during the development of acute excitation focus. MW were recorded predominantly in the frontal and temporal neocortical areas. They appeared as a potential complex consisting of a negative monophasic wave with a superimposed one- or two-phasic spike followed by a 2-3 second theta-delta-burst. MW were recorded in 11 patients of 19 with mesencephalic damages and were not observed in the EEG of the control patients. PMID- 8212873 TI - [The electrophysiological correlates of the involvement in a pathological process of the thalamo-hypothalamic structures of the human brain]. AB - Comparative EEG studies (with the normative data control) were carried out in patients with different anatomic-topographical variants of craniopharyngioma, effecting the hypothalamus (12 patients) and involving thalamo-subcortical structures in the pathological process (17 patients). Characteristics of EEG reorganization were found to be determined in the first instance by the stage of development of the focal process. Analysis of the regional characteristics and intercentral relations of the brain biopotentials revealed besides the common features, the differences in the effects of certain diencephalic structures on the spatial-temporal EEG organization. Hypothalamic areas exert mainly global influence on the EEG pattern formation. Thalamic structures influence genesis of the rhythmic activity forms and their intercentral relations more differentially and make more important contribution to the formation of the balanced (in norm) pattern of the brain electrical processes spatial-temporal organization. PMID- 8212874 TI - [The spatial organization of bioelectrical activity during the treatment of the chronic pain syndrome]. AB - EEG studies with spectral-coherent analysis and evoked potentials recording were carried out in 35 patients with deafferentation pain syndrome before and after pain-relief surgery (DREZ operations). In the cases with a significant anti-pain effect obtained there was an increase of the mean coherence level accompanied by an increase of different frequencies rhythms correlation in symmetrical regions of both hemispheres together with a marked decrease of intrahemispheric connections, especially in the frontal-temporal areas in the theta-range. After the pain-relief surgery the late positive component of somatosensory evoked potential (P220-300) decreased and visual evoked potentials became more clearly detected. Electrophysiological results give evidence on the alterations in the nonspecific afferent system after the pain-relief surgery and weakening of emotional tension. The data may be used as an objective criterion for evaluation of efficiency of surgical interventions in patients with pain. PMID- 8212875 TI - [The characteristics of the bioelectrical activity of the human brain in lesions of different sections of the corpus callosum]. AB - This work represents the results of analysis of EEG, its structure and spreading along the cortex in 44 patients with arteriovenous malformations of the corpus callosum. The method of quantitative EEG analysis was used with computation of the spectral power and intercentral coherence. The results gave a possibility of a comparative evaluation of changes in spontaneous cerebral activity after the lesions in different portions of the corpus callosum (anterior, middle, and posterior) and permitted to characterize their contribution into the genesis of EEG. A conclusion is drown that coherence spectra are a significant parameter reflecting intra- and interhemispheric intercentral relations of electrical brain processes. These connections were more deranged after the lesions of the anterior and the middle portions of the corpus callosum than those of the posterior portion. PMID- 8212876 TI - [The specificity of the recovery processes in the brain of patients with diencephalic and hemispheric lesions (an EEG coherence analysis)]. AB - Inter- and intrahemispheric EEG coherence and its asymmetry was studied in 65 patients with head tumors, 70 patients with head injury before and after surgery. Control characteristics were obtained from 20 healthy subjects. EEG and clinical data were compared in patients with right and left hemispheric tumors. Patients with left hemispheric tumors were characterized by a shorter recovery period (EEG and clinical data), earlier stage of diencephalic activation, and by the right hemispheric asymmetry of EEG coherence. These characteristics were not observed in patients with right hemispheric tumors. Interhemispheric coherence decreased to a higher degree in patients with right hemispheric damages in comparison to those with the left ones, especially in the central leads in the theta-range. In patients with the left foci the maximal interhemispheric coherence decrease was observed in the frontal recordings. Coherence characteristics and their dynamics were shown to be alike in patients with right hemispheric and diencephalic damages. PMID- 8212877 TI - [Interhemispheric asymmetry according to evoked potential parameters in patients with depression]. AB - In depressive patients with different degrees of severity of the disorder hemispheric differences of the occipital and central EP peak amplitude and latency were estimated under the conditions of presentation of a neutral light stimulus, structural stimulus, and mental reproducing the structural stimulus during presentation of the neutral one. Affective responses to the stimuli were also taken into account. In non-psychotic depression hemispheric asymmetry was observed in all responses studied being correlated with the dominant affect. In anxiety most of the EP components were higher in the right hemisphere; in sad affect they were higher in the left hemisphere. In psychotic depression, irrespective of the dominant affect, EP characteristics were higher in the right hemisphere. PMID- 8212878 TI - [The dominant and neurodarwinism]. AB - Lately, the trends analysing the traits of likeness between the evolutionary process, immune reactions and brain activity was called as "neurodarwinism" (G. Edelman). It has been established that pre-existed diversity of the material to be selected is the main condition of successful adaptation of the living organism to unknown future. The review of the data obtained in the course of studying the dominant by V. S. Rusinov's school shows that namely the dominant mechanism does ensure the variety of neuronal and behavioural assortment from which new adaptive behavioural acts are formed. This statement allows to consider further theoretical and experimental study of the dominant phenomenon as one of the priority and promising trends of the modern neurobiology. PMID- 8212879 TI - [The detection of a latent state occurring in the hippocampus after the cessation of long-term potentiation]. AB - The possibility of restoration of long-term potentiation (LTP) due to stimulation of the locus coeruleus and the dorsal raphe nucleus was investigated in the dentate gyrus and the area CA1 of the hippocampus correspondingly. The stimulation parameters were sufficient to evoke behavioral reactions of the freely moving rats. It was shown that the stimulation of the locus coeruleus non effective before tetanization of the perforant path restored the already ceased LTP in the dentate gyrus evoked by tetanization of the perforant path. Also, the stimulation of the dorsal raphe nucleus non-effective before tetanization of the Schaffer collaterals restored the already ceased LTP in the area CA1 evoked by tetanization of the Schaffer collaterals. The mathematical model of LTP restoration is presented based on the existence of several forms of calcium/calmodulin-dependent protein kinase. LTP restoration due to stimulation of the emotiogenic brain structures is considered as a model of emotional reminder phenomenon. PMID- 8212880 TI - [The hypothalamic dominant focus]. PMID- 8212881 TI - [The principle of the dominant in the individual development of an organism]. AB - In the paper the data obtained in the laboratory in the course of the long-term studies are reviewed. The results allowed to establish that the dominanta principle is not only the basis of the nervous system activity but also a regulator of the motor activity of a developing organism at all stages beginning from the zygote, i.e. before the maturation of the nervous system. Attention is paid to the role of the dominanta principle in a realization of the "energetic rule of the skeletal muscles" and hence to its significance as a main factor determining the individual development of the organism. PMID- 8212882 TI - [The thresholds of discriminating the duration of frequency-modulated signals by cats behaving freely]. AB - Threshold values of duration if frequency modulated signals (sweeps) were measured under the free behaviour conditions in cats. Modulation of the sweeps was carried out linearly in a diapason of 2-100 ms with both increasing and decreasing frequency and embedded in tone stimuli with central frequency of 2.5 kHz and total duration of 0.5 s. The sweeping rate was the same in all cases and equal to 1.2 kHz/s. While training, animals had to discriminate "short" (2 ms) signals (heard by a human as clicks) and "long" (100 ms) signals (with well expressed frequency change when hearing). Different durations being used in experiments, at the sweeping duration of 30 ms cats qualified signals as "short" and "long" ones with equal probabilities. The results are similar to those obtained for humans in spite of significant difference in frequency resolution ability for animals and humans. PMID- 8212883 TI - [The cholinoreactive system of the neostriatum and the active avoidance behavior of rats in a T maze]. AB - In experiments with 57 Sprague-Dawley male rats was studied the influence of single right- and left-side injections of different doses of choline agonist carbachol and choline blocker scopolamine into the dorsal part of the neostriatum (the head of the caudate nucleus) on active avoidance conditioning in a T-maze and on the locomotor activity. Non-adequately high carbachol doses disturbed the process of conditioning during the whole training period inducing no significant changes in locomotor activity of the rats. Microinjections of carbachol and scopolamine in small doses did not change the process of T-maze conditioning and also did not influence the dynamics and the level of locomotor activity of the experimental rats in comparison with the control ones. PMID- 8212884 TI - [The effect of long-term adaptation to hypoxia on the open-field behavioral reactions in rats with different types of behavior]. AB - We studied the influence of long-term (30 days) adaptation to hypobaric hypoxia (daily lifting to 5000 m for 5 h) on behaviour of rats with different typological characteristics and levels of resistance to hypoxia. Correlation was ascertained between the resistance of rats to oxygen deficiency and the open field locomotor activity. Adaptation was shown to induce the state of increased anxiety in animals of all the groups under study. In rats with the low resistance to hypoxia adaptation led to increase of exploratory activity. In rats with high initial resistance hypoxic influences caused an increased extinction of orienting reaction at repeated testing in the open field as well as motor excitation increase. In animals with active and medial types of behaviour hypoxic influences increased exploratory activity. In animals with the medial behavioural type increased exploratory activity was changed later by general motor excitation. In rats with the passive type of behaviour adaptation resulted in decrease of the number of rearings testifying to suppression of exploratory reactions, and in the phase changes of locomotor activity. PMID- 8212885 TI - [A comparative study of the asymmetry in the spatial-exploratory behavior of mice in 2 populations]. AB - In two populations of contemporary generations of non-strain mice was found a considerable shift of interhemispheric asymmetry the relative activity of the right hemisphere being increased in comparison with the known data. Quantitative evaluation and the character of this shift in the two populations were different. Changes observed are suggested to be a manifestation of adaptive response of the organism to environmental pollution. PMID- 8212886 TI - [The disparate modulation by mu- and kappa-agonists of the cholinoceptor plasticity of the RPa3 and LPa3 neurons in the snail]. AB - The existence of modulatory opiate mu- and kappa-receptors on the somata of identified RPa3 and LPa3 Helix neurons was shown using double microelectrode voltage clamp techniques. Agonists of these receptors, morphine and bremazocine, inhibit activity of somatic electrogenic cholinoreceptors. The equal quantities of mu-receptors but not kappa-receptors were found on the somata of RPa3 and LPa3 neurons. There were more kappa-receptors on the soma of RPa3 neuron that on the soma of LPa3. Both opioids (50-100 microM) had a reversible influence on an extinction depth of the inward current evoked by a local acetylcholine application into the soma (ACh-current) directions of both opioids' effects being mutually opposite. Morphine deepened the extinction of Ach-current of RPa3 neuron. Bremazocine loosened the extinction of Ach-current of RPa3 neuron and did not influence cholinoreceptor plasticity of LPa3 neuron. PMID- 8212887 TI - [The characteristics of the changes in behavior and hormonal balance in chronically alcoholized monkeys under acute emotional stress]. PMID- 8212888 TI - [The neuronal activity of the motivational-emotiogenic formations of the hypothalamus during a single stimulation of the ventromedial nucleus]. PMID- 8212889 TI - Quantitative flow cytometry: analysis of protein distributions in budding yeast. A mini-review. PMID- 8212890 TI - Effects of growth with ethanol on fermentation and membrane fluidity of Saccharomyces cerevisiae. AB - Saccharomyces cerevisiae HSc was grown with ethanol at concentrations up to 10% (v/v). The immediate effects of additions of externally added ethanol on CO2 production and O2 consumption of washed organisms were studied by stopped-flow membrane inlet quadrupole mass spectrometry. Fermentative activities of organisms grown with ethanol (0-5% v/v) showed similar sensitivities to inhibition by ethanol, whereas those grown with 10% (v/v) ethanol had become protected and were markedly less sensitive. The fluidity of subcellular membrane fractions was measured by determination of the temperature dependence of the rotational order parameter of the spin label 5-doxyl stearic acid (free radical) by electron spin resonance. Mitochondria prepared from yeasts grown with 0, 7, and 9% (v/v) ethanol showed similar overall fluidity, although differences in temperature dependent behaviour indicate altered lipid composition or lateral phase separations. On the other hand the microsomal fraction from organisms grown with 9% ethanol showed a remarkable increase in fluidity. These data suggest that the protective effects of growth with ethanol near the limit of tolerance on fermentative activities may arise from altered plasma membrane fluidity properties. PMID- 8212891 TI - Analysis of the inducer-responsive CAR1 upstream activation sequence (UASI) and the factors required for its operation. AB - Induced production of arginase (CAR1) enzyme activity and steady-state CAR1 mRNA in Saccharomyces cerevisiae requires wild-type ARG80/ARGRI and ARG81/ARGRII gene products. We demonstrate here that these gene products, along with that of the MCM1 gene, are required for the inducer-dependent USAI-A, UASI-B and UASI-C elements to function but they are not required for operation of inducer independent CAR1 UASC1 or UASC2. Through the use of single and multiple point mutations, the CAR1 UASI-B and UASI-C elements were demonstrated to be at least 23 bp in length. Moreover, simultaneous mutation of both ends of an elements gave stronger phenotypes than mutations at either end. The center of the element was more sensitive to mutation than were the ends. PMID- 8212892 TI - The multifunctional regulatory proteins ABF1 and CPF1 are involved in the formation of a nuclease-hypersensitive region in the promoter of the QCR8 gene. AB - The abundant DNA-binding proteins ABF1 and CPF1 are members of a family of global regulators with diverse chromosomal functions in the yeast Saccharomyces cerevisiae. Recent evidence suggests that these protein factors may be involved in establishing and maintaining well-defined chromatin in promoter regions and other genetic elements. We have investigated the involvement of ABF1 and CPF1 in chromatin organization at the QCR8 gene, encoding subunit VIII of the mitochondrial ubiquinol-cytochrome c oxidoreductase. The promoter region of the QCR8 gene contains overlapping binding sites for ABF1 and CPF1. Nucleosome positioning studies indicate that the QCR8 gene is associated with a phased array of nucleosomes under both catabolite-repressed and derepressed growth conditions. Analysis of binding site mutants reveals that both ABF1 and CPF1 are involved in maintaining a nuclease-hypersensitive region in the QCR8 promoter. The chromatin structure at QCR8 during steady-state growth is, however, mainly dependent on binding of ABF1 to the promoter region. Implications of these findings for the role played by ABF1 and CPF1 in the regulation of mitochondrial biogenesis and other processes important for cell growth and division will be discussed. PMID- 8212894 TI - Metabolic studies of a fructose-intolerant yeast by in vivo 31P-nuclear magnetic resonance spectroscopy. AB - The metabolic effects of the administration of fructose to a yeast expressing the cDNA for rat liver ketohexokinase have been investigated by 31P-nuclear magnetic resonance spectroscopy. Cessation of growth suffered by the yeast on exposure to 5 and 25 mM-fructose was accompanied by a large accumulation of fructose 1 phosphate at the expense of cytoplasmic orthophosphate and nucleoside triphosphate. Shifts in resonances were consistent with a drop in cytoplasmic pH. Arresting growth with 1 mM-fructose, however, did not result in these changes, although a large accumulation of fructose 1-phosphate occurred which may have been supported by the mobilization of polyphosphates. PMID- 8212893 TI - Flocculation of Kluyveromyces marxianus is induced by a temperature upshift. AB - An upshift of the growth temperature from 26 to 40 degrees C in the presence of calcium leads to the aggregation of Kluyveromyces marxianus cells and to the formation of flocs. Analysis of cell wall proteins, either by sodium dodecyl sulphate-polyacrylamide gel electrophoresis of extractable mannoproteins or by immunolocalization, revealed an accumulation of a protein with Mr 37 kDa(p37), upon flocculation. Immunological studies confirmed the homology of this protein with the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). When mRNA isolated from cells growing at 40 degrees C was translated in vitro, a 35 kDa newly labelled protein was synthesized and immunoprecipitation assays showed that this protein is recognized by p37-antiserum, suggesting that the 35 kDa polypeptide might be an unglycosylated precursor for of p37. The results indicated that the presence of this cell wall mannoprotein closely related to GAPDH is dependent on the growth temperature, suggesting its role as adhesin. PMID- 8212895 TI - Cloning and characterization of the SEC18 gene from Candida albicans. AB - The SEC18 gene product is required for protein transport at different stages in the Saccharomyces cerevisiae secretory pathway. The homologous SEC18 gene from Candida albicans has been cloned by complementation of a sec18-1 S. cerevisiae thermosensitive mutant using a C. albicans genomic library in YRp7. Sequence analysis of the gene revealed a 2382-bp open reading frame which coded for a protein of 88,926 kDa. By an in vitro transcription-translation coupled reaction of the C. albicans SEC18 gene, a protein of approximately 85 kDa was obtained. Hydrophobicity analysis of the protein did not show any predicted signal sequence nor transmembrane anchor domain. These results and the fact that glycosylation was absent in the protein indicated that C. albicans Sec18p did not enter in the secretory pathway. The alignment of the amino acid sequence revealed that the SEC18 gene from C. albicans was homologous to the SEC18 from S. cerevisiae (50% amino acid identity) and to the gene that coded the N-ethylmaleimide-sensitive factor (NSF) protein (43% amino acid identity). Moreover, the C. albicans Sec18p also showed the putative ATP binding site present in S. cerevisiae Sec18p and in NSF. PMID- 8212896 TI - Linguistic analysis of chromosome III DNA sequence of Saccharomyces cerevisiae. AB - The analysis of the Saccharomyces cerevisiae chromosome III DNA sequence by computer ('in silico') permits the definition of its linguistic characteristics. These characteristics include the designation of non-randomly occurring oligonucleotides, their distribution along the chromosome, and the distribution of some particular homopolymers. All these elements may contribute to the understanding of the organization of information on the chromosome. PMID- 8212897 TI - Isolation and DNA sequence of the STE14 gene encoding farnesyl cysteine: carboxyl methyltransferase. AB - We isolated a mutant defective in C-terminal farnesyl cysteine:carboxyl methyltransferase activity from a screen for mutations causing a-specific sterility. A genomic fragment was cloned from a yeast multi-copy library that restored mating. Both the cloned gene and the sterile mutation were allelic to the STE14 gene. A ste14-complementing 2.17 kb BamHI fragment subclone was sequenced and found to encode a 239 amino acid protein with a molecular weight of 27,887 Daltons. The hydrophobicity profile of the methyltransferase reveals the presence of at least five potential transmembrane domains. In comparisons of the C-terminal methyltransferase amino acid sequence with those in the PIR and Swiss protein databases, no significantly similar sequences were found nor were conserved regions from other methyltransferases present. PMID- 8212898 TI - Sequence and function analysis of a 4.3 kb fragment of Saccharomyces cerevisiae chromosome II including three open reading frames. AB - The nucleotide sequence of a fragment of 4337 base pairs of Saccharomyces cerevisiae chromosome II has been determined. The sequence contains three open reading frames, one of them being incomplete. Deletion analysis showed that YBR12.31 is essential for yeast growth, while deletion mutants of YBR12.32 and YBR12.33 are viable. YBR12.33 is identical to SMY2, isolated as a suppressor of a myo2 mutant (Lillie, S.H. and Brown, S.S., unpublished, EMBL M90654). PMID- 8212899 TI - Cloning and sequence of ADP-ribosylation factor 1 (ARF1) from Schizosaccharomyces pombe. AB - A gene encoding a homologue of the ADP-ribosylation factor (ARF) family of small GTP binding proteins was cloned from a Schizosaccharomyces pombe cDNA library by a functional screen of suppressors of sensitivity to 3-aminotriazole in a gcn3 null strain of Saccharomyces cerevisiae. Two independent isolates each contained the full coding region of the ARF1 gene. The encoded SpARF1 protein has a predicted molecular weight of 20,618 and is 88% and 79% identical to human and S. cerevisiae ARF1 proteins, respectively. As independent isolates were obtained, this effect of the SpARF1 appears to be a real phenomenon, but cannot currently be easily understood within the context of the evidence for a role(s) for ARF proteins in the protein secretory pathway. PMID- 8212901 TI - Current awareness on yeast. PMID- 8212900 TI - CLG1, a new cyclin-like gene of Saccharomyces cerevisiae. AB - A region of chromosome VII adjacent to SKI8 has a 453 amino acid open reading frame whose sequence has significant similarity to that of HCS26, a G1 cyclin. A disruption mutation of this open reading frame has no apparent phenotype under the conditions tested. ORFD, an open reading frame adjacent to the CDC48 gene, is even more similar to HCS26. PMID- 8212902 TI - Detection and identification of the cross-linking amino acids N tau- and N pi-(2' amino-2'-carboxy-ethyl)-L-histidine ("histidinoalanine", HAL) in heated milk products. AB - An unknown ninhydrin positive compound, X, was detected in acid hydrolysates of heated skim milk samples by amino acid analysis, eluting between phenylalanine and pyridosine in the chromatogram. The formation of X correlated with heating time and temperature. preparative ion-exchange chromatography enabled the isolation of X and a second minor compound from a milk protein hydrolysate and from a model mixture consisting of N alpha-acetylhistidine and methyl-2 acetamidoacrylate (acetyldehydroalaninemethylester), in a relative abundance of 8 to 1. By 1H-NMR spectroscopy, the two compounds could be identified as the N tau- and N pi-isomers of N-(2'-amino-2'-carboxy-ethyl)-L-histidine (histidinoalanine), a cross-link amino acid that has not been described in food proteins up to now. In a number of foods containing milk protein, the N tau-histidinoalanine contents were between 50 and 1800 mg/kg protein, which is in a concentration range comparable to the potential nephrotoxic cross-link lysinoalanine, which was determined simultaneously. PMID- 8212903 TI - Monitoring cheddar cheese ripening by chemical indices of proteolysis. 3. Identification of several high-molecular mass peptides. AB - Two Cheddar cheeses from two different production plants were ripened over 24 weeks at 10 degrees C and then analysed for peptides soluble in citrate buffer at pH 4.6 by reversed-phase (RP)-HPLC. Thirteen peptides with a chain length of between 35 and 65 amino acid residues and molecular masses between 3800 and 7400 were isolated and assigned to the corresponding amino acid sequences of the casein fractions via Edman degradation and amino acid composition. All peptides were fragments of the region K29-S96 of beta-casein A1 and A2, and eleven of them had M93 as the C-terminal. The amounts and proportions of these peptides varied differently during ripening of the two cheeses, so they may be suitable markers for characterizing the stage of ripening. PMID- 8212904 TI - The levels of cadmium, nickel, manganese lead, zinc, iron, tin, copper and arsenic in the brined canned Jordanian cheese. AB - The levels of cadmium, nickel, manganese, lead, zinc, iron, tin, copper and arsenic in fresh sheep's milk, white brined cheese preserved in glass jars and in tin containers and their corresponding brines, salt and tin plates were determined by atomic absorption spectrophotometry. The results have been compared with those reported in recent years. Although metal levels were comparable with other investigators' data, our data shows that white brined cheese picked-up metals from tin containers and from the naturally contaminated salt, on the contrary brined cheese in preserved glass jars showed lower levels of metals. We recommend a purified salt for brine preparation and glass jars for white cheese preservation in order to minimize cheese contamination with metals from tin cans and salt. PMID- 8212905 TI - Kinetics of thermal degradation of thiamine and surface colour in canned tuna. AB - The kinetics of thermal degradation of thiamine and surface colour (lightness measured as Hunter L-value) in canned white tuna were determined using an unsteady-state experimental procedure. Kinetic parameters were calculated by weighted non-linear regression considering a first-order kinetic model with a dependence of the kinetic coefficient (D) with temperature of the Thermal Death Time (TDT) type. Mass-average retentions of thiamine were calculated using a mathematical model which takes into account the non-uniform and unsteady distribution of temperature inside the container during thermal processing. The high correlation obtained between the predicted and the observed retention values and the small confidence intervals found for the kinetic parameters indicate a high statistical reliability. The kinetic model thus determined permits the simulation and optimization of the process resulting in a better quality of the final product. PMID- 8212906 TI - Meta-analysis of environmental and occupational epidemiological studies: a method demonstrated using the carcinogenicity of PCBs as an example. AB - A method for a meta-analysis of several environmental or occupational epidemiological studies with small prevalences and/or incidences and long latency periods is presented. A combination of statistical evaluations of small prevalences should be done in the following way: (1) selecting relevant and comparable studies, (2) computing exact p-values of Poisson tests and aggregating them by Fisher's method, (3) estimating overall relative risks (or SMRs) by pooling the data of the individual studies and by using weighted sums of the logarithms of the individual risks, and (4) calculating confidence intervals and confidence curves for the overall risks. An example illustrates this technique by investigating the association of exposure to polychlorinated biphenyls (PCBs) at work and cancer mortality in men. PMID- 8212907 TI - Increased risk of acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) in a county of Hesse, Germany. AB - The incidence of acute and chronic myelogenous leukemia has been compared for the two neighbouring regions of Marburg and Giessen in Hesse (Germany). The investigation was based on the incident cases of the years 1983-1989 which have been diagnosed in the hematological departments of the universities of the two regions. The epidemiological evaluation of the data has been carried out in terms of a historical follow-up study, and shows an increased relative risk for the region around Marburg with a particular elevation for one community within this region. Potential determinants are discussed and focus on trinitrotoluene (TNT) and decomposition products which are known to contaminate the soil of this community, in some places severely, due to insufficient removal of remnants of the TNT production in large underground plants during World War II. PMID- 8212908 TI - Childhood leukaemia in Switzerland: comparison of different sources of data. AB - Since 1976 the Swiss Paediatric Oncology Groups (SPOG) has registered leukaemia cases occurring in Switzerland. The registration was set up for clinical research; however, since 1985 efforts have been made to complete the registers with cases not taking part in a clinical trial. The data of the SPOG register between 1976 and 1989 are compared to data from cancer registers and the mortality statistics of the Federal Office of Statistics. Between 1985 and 1988 the SPOG register included 91% of the cases recorded by the six cantonal registries. Compared to mortality data, registration was 100% in 1989. The SPOG data file can therefore be assumed to be complete enough to be used for epidemiological studies on incidence of leukaemias and on time trends of leukaemias in Switzerland. PMID- 8212909 TI - [Dietary intake of total lipids and saturated fatty acids of the Geneva population: an unexpected development]. AB - Results of two dietary surveys performed 10 years apart suggest that the Geneva population has a lower caloric intake and a lower proportion of total fat and saturated fat in the total caloric intake. These changes are observed in all ages, sexes or nationalities. They may indicate that prevention campaigns promoting a healthier diet with a lower content of calories and fat have had some impact. However, because of methodological differences between the two surveys we cannot conclude that these dietary changes are real. PMID- 8212910 TI - [The Swiss population and drug problems: perception of the problems and proposals for solutions]. AB - The aim of this study is to investigate which problems in relation with drug abuse are considered to be the most important by the Swiss population and which measures do they support to reduce them. Base for this study are the results of a representative telephone survey realized in october 1991 with 1004 Swiss residents. People are mostly concerned with problems related to the danger for youth and those concerning public order but also with the human condition of addicts. Drug addicts are considered as people who have lost the sense of live, as sick but also as dangerous and less truthful. Supported are overall prevention, offers for therapies, the repression of trafficking and money laundering but not of drug users as well as measures going in the direction of harm-minimisation (shooting rooms, medical prescription of drugs). Younger people, those with higher education and the german-speaking population have a more positive view of drug addicts and support measures in the sense of harm minimisation. Elder people and the french-speaking population have a rather negative view of drug addicts and don't favour measures for harm-minimisation. PMID- 8212911 TI - A multivariate example of case-cohort analysis: neonatal mortality in Switzerland, 1979-81. AB - A study of all births in Switzerland during the years 1979-81 is used to illustrate the advantages of the case-cohort design for this epidemiologic analysis of neonatal mortality. The example shows that familiar associations between infant mortality and explanatory variables such as sex and weight at birth can be precisely estimated using only a sample from the full cohort. PMID- 8212912 TI - [Mortality of foreign and indigenous population in the German Federal Republic]. AB - Comparative mortality studies with respect to nationality have not yet been published in a comprehensive way for the Federal Republic of Germany. A recent special analysis of causes of death for German mortality statistics of the year 1986 indicates a lower mortality risk among the migrant compared to the indigenous population. Apart from potential biases, such as underreporting of nationality of death cases or overestimation of the size of the non-indigenous population in Germany, from the perspective of socio-epidemiology the possibility arises that selection processes lastingly affect the mortality risk of migrants. The dependence of the length of stay from the quality of the state of health or rather a plausible increased likelihood of remigration in case of chronic disease may constitute important influences, which could explain the differences in mortality between indigenous and migrant population. PMID- 8212913 TI - [Perception of traffic noise emission in Basel City canton in comparison to actually measured noise levels]. AB - The objective of this study was to assess to what extent the subjective annoyance is influenced by the actually measured or calculated street traffic noise and by sociodemographic factors. In the study on air pollution and health in Basle a representative sample of 1033 families with children up to five years were asked how they perceived street traffic noise. The extent of annoyance was assessed with a scale from 0 (no annoyance) to 10 (unbearably annoyed). The actual noise levels were taken from the official noise-register. Nearly 30% of the families were exposed to > 65 dB(A) in daytime. Immigrant families as well as participants with low education more frequently lived in streets with higher noise levels than Swiss families or participants with higher education. 16.4% considered themselves heavily annoyed by traffic noise (scale 8-10). The proportion of heavily annoyed participants was positively correlated with the actual noise levels, the slope was steepest at a noise level between 60-65 dB(A). By means of a multiple regression it could be shown that, adjusting for education level and city district, the actual noise level was the best predictor of subjective annoyance. PMID- 8212914 TI - [Cost expansion of the health system as a risk process]. AB - Cost expansion in health care has been an issue of health policy for almost 20 years. Also after the health reform act of 1988 this has not changed remarkably. On the one side this may be due to pressure groups that block effective cost constraining politics. On the other side, however, scientific approaches are insufficient in explaining this phenomenon. Models of health economics often assume a one-sided cost/benefit-rationality of the health care sector. Also sociological attempts that emphasize the "Eigen"-rationality of the health system frequently cut short the problem for instance as "Selbsthypostasierierung". This paper deals with the question to what extent can cost expansion be regarded as a product of societal context conditions. Using risk-theoretical and systems theoretical approaches it is shown that the interaction of separated subsystems builds up a growing risk potential that comes out among other things as cost expansion. This includes the risk of crashes of the social structure which might result in the loss of generally equal access to health care. PMID- 8212916 TI - AIDS surveillance in Europe: status at 31st December 1992. PMID- 8212915 TI - A cross-sectional study on vaccine coverage and seroprevalence in schoolchildren in Andorra. AB - A cross-sectional study on vaccine coverage and vaccine effectiveness was carried out on a randomized sample of the cohort of schoolchildren born in 1983 attending school in Andorra, prior to the introduction of a Systematic Immunisation Plan that included centralised import and delivery of vaccines to vaccinating clinics, surveillance of the cold-chain during vaccine delivery, and a clearly-defined immunization schedule against diphtheria, tetanus, -pertussis, polio, mumps, rubella and measles. Vaccine coverage was estimated from vaccination card records; history of disease and sociodemographic variables were obtained through a questionnaire to the children's parents and vaccine effectiveness was estimated through serum antibody testing. Vaccine coverage levels for DTP and OPV were 97.8% for both. Protective serum antibody prevalence was correspondingly high except for the polio viruses. The authors suggest that decreased vaccine effectiveness, probably due to poor preservation of the cold chain, might be the cause of this finding. In countries or regions with an otherwise developed organisation of health services, an important issue like this can still be overlooked. PMID- 8212917 TI - WHO declares tuberculosis a global emergency. PMID- 8212918 TI - [Potential influence of nutrition with supplements on healthy and arthritic joints. II. Nutritional quantity, supplements, contamination]. AB - A short period of fasting leads, in the mouse, to usually reversible damage to chondrocytes and in patients with rheumatoid arthritis often to a temporary improvement. Slight hypo-alimentation and a low-caloric diet reduce the spontaneous development of osteo-arthritis in the mouse, whereas a high-caloric diet promotes the disease. In man, mice, and, in particular, fattened animals, obesity is often associated with forms of osteo-arthritis. In such cases, it may be assumed that metabolic damage to cartilage is involved as well as damage due to weight-bearing forces. Elderly people, i.e., persons with a predisposition to osteo-arthritis, often suffer from a generalized vitamin deficiency. Vitamins E, B2, and C have been shown to exert an inhibitory effect on osteo-arthritis in animals, and it has been found that supplementation therapy, particularly with vitamin E and the combination of vitamins B1, B6, and B12, can exert a beneficial effect on the symptomatology of human degenerative joint disease. Mineral deficits in calcium, zinc and selenium (Kashin-Beck disease; endemic osteo arthritis deformans) can provoke skeletal damage in humans and animals. On the other hand, calcium, iron, and copper have been reported to give rise to storage diseases, in some cases with involvement of articular cartilage. There have been indications that chondrotoxic damage may result from food contaminants. So far very little is known about the influence of phytopharmacodynamic substances (other than derivatives of rutin and rhein) on osteo-arthritis. The large gaps in our knowledge of the chondrotropic properties of the constituents of food and common stimulants underline the need for further investigations. PMID- 8212919 TI - [Yersinia arthritis. Long-term follow up]. AB - Twenty-two patients were followed for a mean of 10.7 years after acute Yersinia arthritis. Their clinical course, agglutinating antibodies, and laboratory parameters of inflammation were analyzed. In 73% of cases HLA-B27 was positive. The acute disease lasted from 1 month to 1 year. One male patient showed a bilateral synostosis of sacroiliac joints at the acute phase of the disease. He developed the clinical characteristics of severe ankylosing spondylitis. Another two patients with HLA-B27 had radiologically inflammatory changes of sacroiliac joints or symphysis without clinical findings. Agglutinating antibodies against dead Yersinia bacilli were negative in all patients. No laboratory signs of inflammation were present. The long-term prognosis of Yersinia arthritis is benign. PMID- 8212920 TI - [Expanded anamnesis and psychodiagnostic classification of psychosomatic rheumatic patients. I: Anamnestic indications of psychosomatic correlations with manifestations of the locomotor system]. AB - The author describes the information gained from anamnesis which points to a psychogenetic cause of rheumatic complaints. These symptoms are part of the diagnostically important criteria which must be supplemented still further by means of a personal discussion with the patient. A great deal depends on the skill of the physician in conducting these talks, with regard to obtaining relevant information on personal problems which may be underlying the disease patterns. Of course the possibility of a connection of the detected problems with the clinical picture should be given. PMID- 8212921 TI - [Expanded anamnesis and psychodiagnostic classification in psychosomatic rheumatic patients. II: A recommendation for diagnostic classification of psychosomatic disorders of the locomotor system]. AB - This paper tries to associate psychosomatic manifestations of the locomotion system to one of the following four diagnosis: 1) conversion disorder, 2) anxiety disorder, 3) depressive mood disorder, 4) somatization disorder. For each of these diagnosis definition, clinical manifestation, diagnostic and differential diagnostic criteria are mentioned. The diagnostic criteria can easily be associated to the new ICD-10 (V)F diagnosis. PMID- 8212922 TI - [Cartesian dualism or alchemy of medical routine practice]. AB - Whereas alchemy postulated the unity of body and soul as early as in the 15th century, Rene Descartes developed an artificial separation of the body from the soul in the 17th century, a challenge that today's doctors continue to face. This problematic nature of dualism seems to be suitable for complicating the doctor's relationship with patients of different age groups. With the help of a screening technique and a semi-standardized interview 100 patients (25 women with RA aged > 65; 25 women with RA aged < 55; 25 women aged < 65 without RA and 25 women aged < 55 without RA) were examined with regard to their basic needs in the relationships with their doctor. The patients older than 65 showed characteristic psychophysical particularities and, as compared with patients younger than 55, 86% of them articulated the needs for security as primary need in the relationship with their doctor. Seventy-six percent of the younger patients articulated the need for passing on of information as primary need. To understand the world of the elderly means the handling of pseudo-morbidity, reduced capability, social death and disease as normality, means the acceptance of the need for a mainly emotional doctor-patient relationship. From the results efficient psycho-therapeutical findings can be recommended for the doctor's practical work with regard to "pitfalls," as well as for use as the basis for talks and for a method to use in dealing with elderly people. PMID- 8212923 TI - Transient increase of aminotransferases in RA patients treated with methotrexate. AB - Sixty-two patients with rheumatoid arthritis (RA) were treated with methotrexate (MTX) for 3 months. Methotrexate was given orally in a single dose of 7.5-15.0 mg/week. At the onset of the treatment increased activity of aminotransferases has been observed. Eighteen patients (29%) displayed higher enzyme activity in the first 3 weeks. Despite the continuous drug administration the activity of aminotransferase became normal at week 12 in all but one patient. In this patient MTX had to be withdrawn. PMID- 8212924 TI - [Pathological patella fracture in gout tophus]. AB - Although gout is known to cause destruction of bone by the deposition of tophaceous material, the documented cases of pathologic fractures due to gout are rare. We report the case of a pathologic fracture of the patella. Union of the fracture was seen at 3 months after surgery. PMID- 8212925 TI - S. Freud (1918): turnings in the ways of psychoanalytic therapy--a discussion 75 years later. PMID- 8212927 TI - ["It is not all gold..."]. PMID- 8212926 TI - ["Disciplined uniform analysis" and psychoanalysis of combat neuroses]. PMID- 8212928 TI - [Discussion of S. Freud (1918)]. PMID- 8212929 TI - ["Uniform analysis" never existed, she is like "flying Dutchmen", of which we save a few]. PMID- 8212930 TI - [Changes in psychoanalysis--what has value?]. PMID- 8212931 TI - [Freud's "Paths of psychoanalytic therapy"--75 years later]. PMID- 8212932 TI - [Misunderstandings of a concept]. PMID- 8212933 TI - ["Paths of psychoanalytic therapy and the pure gold of psychoanalysis". Comments on Freud's (1918) "Paths..."--75 years later]. PMID- 8212934 TI - [Therapeutic and scientific blind alleys in correlation with Freud's gold-copper metaphor]. PMID- 8212935 TI - [Importance and determinants of early mother-child relations]. AB - In a prospective longitudinal study on child development from birth to age eight 362 first-born infants and their families were investigated. The subjects were distributed across the nine cells of a two-factorial design, factor 1 representing the degree of organic, factor 2 the degree of psychosocial risk. At age 3 months mother-child interaction was videotaped and evaluated with microanalytic technique. The quality of MCI could be demonstrated to be as predictive for later cognitive development as early developmental tests. Social emotional problems of the toddler and preschool child was predicted better by parameters of early MCI than by temperament. Disturbed interactions were associated with later cognitive retardation and enhanced behavior problems. MCI is significantly determined by neglect and rejection, which showed typical behavioral patterns. The early separation of mother and high risk newborn itself did not lead to alterations in maternal attachment. Compared with mother daughter dyads early interaction of mother and son was characterized by more reactivity and positive emotion. PMID- 8212936 TI - [Results of infant research and its clinical relevance for psychoanalysis with reference to the concept of intentionality (Schultz-Hencke)]. AB - The reception of results put forward by empirical infant research has been gaining increased significance for Psychoanalysis. This applies to analytic theory formation as well as to the clinical-therapeutic field. In this context convergencies between Schultz-Henckes concept of intentionality and new views in analytic developmental theory seem to emerge. The paper presented discusses before this background the significance of the visual domain, the affects and the explorative motivational system. The consequences of pathogenic impacts within these fields shall receive special consideration with regard to later neurotic developments. PMID- 8212937 TI - [Depersonalization and self-injury]. AB - Patients with deliberate self harm syndrome and with factitious disorders often describe depersonalisation phenomena, during which they have a diminished pain sensitivity or analgesia. The self-mutilating act can stop the depersonalisation temporarily. Concerning the psychodynamic processes there are common traits between depersonalisation and self-mutilation. The connections between depersonalisation and self-mutilating behaviour are described. Depersonalisation is understood as a defense mechanism, ranging between mature and immature defense mechanisms. An illustrative case is demonstrated. PMID- 8212938 TI - Filamentous fungi and mycotoxin detected in coconut. AB - Fifty-nine species and one variety belonging to 25 genera of fungi were isolated from 25 coconut samples on glucose-Czapek's (25 genera and 55 species + 1 variety) and dichloran-glycerol (8 genera and 32 species + 1 variety) agar media at 28 degrees C. The common fungi on both media used were Aspergillus flavus, A. niger, Penicillium chrysogenum and Cladosporium cladosporioides. On glucose Czapek's agar, A. flavus var. columnaris, P. oxalicum, Alternaria alternata, Rhizopus stolonifer and Trichoderma hamatum were recorded as common fungi while A. sydowii and Eurotium chevalieri were isolated with high frequency only on dichloranglycerol medium. Chromatographic analysis of the chloroform extracts of the coconut samples revealed that 5 out of 25 samples tested were naturally contaminated with aflatoxin B1 (15-25 micrograms/kg) and 3 samples contaminated with ochratoxin A (50-205 micrograms/kg). PMID- 8212939 TI - Effects of potassium sorbate on growth and penicillic acid production by Aspergillus ochraceus and Penicillium aurantiogriseum. AB - The effect of potassium sorbate on the growth and penicillin acid production of Aspergillus ochraceus and Penicillium aurantiogriseum was studied. Yeast extract sucrose (YES) broth at initial pH values of 5.5 or 7.0, and containing different concentrations of potassium sorbate was inoculated with fungal spores and incubated for 35 days at 28 degrees C. In all cases, although the pH changes in sorbate-containing media were delayed, patterns were similar to those of the cultures without sorbate. This was most evident when the highest concentration of potassium sorbate was used. Potassium sorbate also inhibited mycelial growth. Penicillic acid production was initially delayed by the presence of potassium sorbate but this inhibition was eventually overcome (30-35 days) and penicillic acid levels at the end of the experiment were similar or higher then the controls. Generally cultures growing in culture media at an initial pH of 5.5 produced less toxin than those growing at pH 7.0. PMID- 8212940 TI - [Serous papillary cancer of the peritoneum: a multicentric primary disease]. AB - Protocols and histologic slides of 258 patients who underwent surgery for the diagnosis of an ovarian carcinoma from 1980 to 1987 at the University Hospital Charlottenburg/Berlin and from 1987 to 1990 at the I. University Women's Hospital Munich were reexamined. 12 out of 165 patients with a serous carcinoma were classified under the diagnosis of a peritoneal serous papillary carcinoma with minimal or absent ovarian involvement. These cases could be differentiated from patients with primary serous ovarian carcinomas by the sole existence of progressed FIGO stages. Especially the picture of small disseminated nodes could be seen. The excessive involvement of pelvic and paraaortic lymph nodes was impressive as well. The peritoneal carcinomatosis consisting of small nodes in our opinion could best be explained by in situ orthotopic multifocal growth. We were able to prove the in-situ genesis of these lesions in 6 of 12 cases by histologic examination. In this group of patients with peritoneal primary serous carcinoma we find the example for a multifocal disease originating from the coelomic epithelium. PMID- 8212941 TI - [Integration of Doppler ultrasound into the obstetric department of a gynecologic clinic]. AB - This study was performed to evaluate the time interval for Doppler ultrasound and sonographic diagnostic measurement at 267 patients during antenatal risk screening. Time for biometry, screening of malformation, Doppler ultrasound, documentation and discussion with the patients were measured. Although experienced colleagues used an standardized inquiry a mean time interval of 52 minutes were needed under optimal conditions. It is interesting to note that outstanding disturbance factors extend the examination time considerable. Many data must be calculated and recorded by the obstetrician. Several proposals are drawn up and discussed in this paper on the basis of this results. This study shows that high special knowledge and a large time expense is necessary to establish Doppler technology in the routine antenatal screening. PMID- 8212942 TI - [Effect of birth interval on the rate of cesarean section for the second twin after vaginal delivery of the first twin]. AB - Cesarean section for delivery of the second twin after successful vaginal delivery of the first twin is an infrequent and unusual occurrence. But this management of twin delivery has increased during the last years. A series of 371 pairs of twins born between 1978 and 1991 were reviewed. 12 second twins (3.2%) were delivered by cesarean section after vaginal delivery of the first twin. The initial 20 minutes the main indications were fetal distress and prolapsed umbilical cord. Beyond the first 20 minutes malpresentations were more frequent. In this group we have seen a better fetal outcome. An influence of the interdelivery time on the cesarean section rate of the second twin was not noted. No significant differences were seen for neonatal morbidity for all 197 vaginal delivered second twins with increasing interval. PMID- 8212943 TI - [Attitude of patients to chorionic villi biopsy: motivation for the decision and perception]. AB - 56 patients with CVS were asked with a standardized questionnaire why they decided to undergo that surgical procedure and how they felt about it. 52 patients said, that their main motivation for CVS was the early diagnosis of a healthy baby. The low health risk of an early performed abruption in case of fetal abnormalities played a secondary role. Concerning the severity of that surgical procedure 44 patients thought, that it was harmless or tolerable and no woman had the feeling that CVS is a fearful intervention. 76% said, that CVS was not painful or only a little bit, 2 patients had the feeling of a painful surgical procedure. The most disagreeable moment during CVS was the hooking of the cervix. There were different opinions comparing CVS stress to amniocentesis stress in patients with a preceding amniocentesis. PMID- 8212944 TI - [Menarche, orgasmic capacity and coitarche]. AB - A group of 609 Czech 16 to 18 years old girls was divided according to the age of the first menses into three subgroups: first with menarche between 10 to 12 years, second in 13 and 14 years, third in 15 and 16 years. It was found that the age of menarche did not distinctly influence the course of their sexual development during the puberal period. The mean age of first rendezvous and coitarche did not significantly differ between the followed three subgroups. Out of the whole group of 609 probands 304 girls already had sexual intercourse. The percentage of coitally orgastic girls was highest in the subgroup with an early first menstrual bleeding between 10 and 12 years of age and the difference to the other two subgroups with a later menarche was statistically highly significant (p < 0.005). The opinion is expressed that changes in brain which enable girls to fall in love for the first time are from the point of view of biological prerequisites more important for the beginning of full sexual life in pubertal girls than hormonal development manifested by first menstrual bleeding. PMID- 8212945 TI - [Conservative treatment of HELLP syndrome]. PMID- 8212946 TI - Valuable indicators of physical stress in porcine plasma. AB - Various markers for stress were evaluated in the plasma of pigs. Treadmill exercise was chosen as a well defined and quantifiable stressor. One group of non stress-susceptible pigs had to carry out two intense exercise bouts at a one-week interval, and another group remained in their pens and served as controls. Large interindividual differences in the performance and in the hormonal and metabolic responses to exercise were observed. The exercise stress resulted in an immediate increase in the plasma concentrations of cortisol, lactate and hypoxanthine, with a return to the pre-exercise levels within one hour. No direct effect of physical stress on CBG binding capacity or on the concentrations of xanthine and uric acid was observed. In two very nervous pigs, even mild stress in connection with the first blood sampling resulted in an elevated concentration of lactate, but the cortisol and hypoxanthine values remained at the basal level. It is concluded that plasma concentrations of cortisol, lactate and hypoxanthine are valuable markers for physical stress. PMID- 8212947 TI - Medetomidine sedation in sheep. AB - The sedative effect of medetomidine was evaluated in 6 male Awassi sheep. Medetomidine at 40 micrograms/kg, i.m. induced sedation and recumbency in the sheep within 9 +/- 1 and 17 +/- 4 minutes, respectively. The duration of recumbency was 58 +/- 1 minutes. Medetomidine produced good analgesia and marked muscle relaxation in the recumbent animals for 30 to 45 minutes. The side effects of medetomidine were bradycardia, respiratory depression, stasis of the rumen with tympany, salivation and polyuria. The animals recovered from the sedative and side effects of medetomidine 1.5 to 2 hours after gaining the righting reflex without any apparent adverse effect. The results suggested that medetomidine could be a useful sedative analgesic in sheep. PMID- 8212948 TI - Blood pressure in the sow: an attempt of indirect measuring ante partum. AB - Farrowing disorders in the sow have detrimental consequences in pig farming and many points of the condition still remain obscure. It was suggested to investigate blood pressure since this might provide an early indication of farrowing disturbances. A first study involved 29 pregnant sows. Blood pressure was measured indirectly using a pediatric occlusive cuff unrolled around the base of the tail and connected to a manometer. The recordings were made on resting sows in recumbent position. The disposal was considered suitable. The values obtained showed a good repeatability. Then a prospective survey involving 122 sows was undertaken. Blood pressure was measured at the 111th day of pregnancy. Systolic values ranged from 89 to 142 mm Hg (mean: 112.4). Physical profile of the sows (weight, backfat thickness) slightly influenced systolic level. On the other hand the sows obtaining the lowest values for systolic pressure were more prone to develop a prolonged farrowing. According to the lack of a parallel direct blood pressure measurement, these results have to be taken with caution. The perspective of early detection of "at risk" individuals with respect to MMA through blood pressure measurement, needs further work. PMID- 8212949 TI - Influence of food deprivation on SCFA and electrolyte transport across sheep reticulorumen. AB - Net absorption rates for SCFA, sodium, chloride, magnesium, and water were measured in the temporarily isolated and washed reticulorumen of sheep. The animals were either fed hay ad lib. plus concentrates once daily or were deprived of food for two days. Food deprivation led to decreased net absorption of all the substances tested. Comparing the solutes, the relative decreases varied between 43% (butyrate) and 56% (acetate). The decrease in solute absorption was accompanied by diminished water absorption. It is concluded that the reduction in absorption may be beneficial for the animal in that energy consumption is diminished and the reservoir function of the forestomach will be maintained longer. However, the reduced absorptive capacity may lead to a deficiency of magnesium, which is thought to be absorbed mainly by the forestomachs. PMID- 8212950 TI - Immune functions of veal calves fed low amounts of iron. AB - Immune functions were studied in male calves fed milk replacer (MR) containing 10 or 50 mg iron (Fe)/kg. Calves fed 10 mg Fe/kg MR developed marked hypoferremia and anemia, whereas serum-Fe and haemoglobin concentration of calves fed 50 mg Fe/kg MR were normal. Growth performance was reduced, while feed/gain ratio, incidence of infections (especially pneumonias), febrile body temperatures and antibiotic treatments were higher in calves fed 10 than 50 mg Fe/kg MR (p < 0.05). Whereas antibody production (to horse erythrocytes) and lymphocyte stimulation (by mitogens) were not significantly altered, cell-mediated immunity (measured as cutaneous delayed-type hypersensitivity reaction to dinitrofluoro benzene), number of neutrophils with phagocytic capacity, activity of the Fe containing enzyme myeloperoxidase, blood serum IgG concentration and the number and diameter of germinal centres as a measure of the number and production of B cells in cervical superficial lymph nodes in calves fed 10 mg Fe/kg MR were reduced when compared with calves fed 50 mg Fe/kg MR (p < 0.05). In conclusion, severe Fe deficiency caused reduced growth performance, associated with and partly due to higher incidence of infections because of defective immune reactions. PMID- 8212951 TI - The morphology of synovial grooves (Fossae synoviales) in joints of cattle of different age groups. AB - The joint cartilage of the head of the radius, the metacarpal bone, the tibial cochlea, the proximal trochlea of the talus and the metatarsal bone of 26 cattle in the age groups fetuses, 0 days, 2-5 weeks, 2-5 months, 7-13 months, 2-3.5 years, and 5-7 years were examined macroscopically and histologically. Synovial grooves developed on all joint surfaces examined, but at different times. At some locations the development of the grooves began prenatally. During the groove development the same features were in principle observed on all joint surfaces: Degeneration and progressive thinning of the joint cartilage, invasion of connective tissue into the cartilage, cessation of the endochondral ossification, and depression of the groove area into the subchondral bone. The findings indicated that the synovial grooves should be considered as being part of the normal morphology of the joints. In 4 animals aged from 3 weeks to 13 months dyschondroplastic (osteochondrotic) lesions were observed in the joint cartilage both inside and outside the groove areas on one or more joint surfaces. PMID- 8212952 TI - Acute metabolic and hormonal effects of intravenously administered sodium n butyrate in untreated and alloxan-diabetic sheep. AB - Experimental diabetes was induced in 4 wethers of the Mutton Merino breed by intravenous injection of alloxan (75 mg.kg-1) in order to determine its impact on plasma glucose, immunoreactive insulin, free fatty acids (FFA), cholesterol, phospholipids, triglycerides, D-(-)-3-hydroxybutyrate (D-3-HB), bilirubin and aspartate aminotransferase (ASAT) as well as on the changes of these parameters brought about by an intravenous infusion of sodium n-butyrate (1 mmol.kg-1). Alloxan administration caused a significant elevation of plasma glucose, FFA, triglycerides, cholesterol, phospholipids, D-3-HB and bilirubin and a decrease of the level of immunoreactive insulin. The increase in glucose level brought about by a bolus injection of sodium n-butyrate in untreated sheep did not appear in alloxanized animals. Thus, it is suggested that the lack of hyperglycaemic response in diabetic sheep was due to the absence of liver glycogen stores. Unexpectedly in alloxan-diabetic sheep, a decrease in the plasma level of FFA occurred after the administration of sodium n-butyrate. Therefore, it may be assumed that beside insulin other factors may contribute to the decrease of FFA under these conditions. PMID- 8212954 TI - [Physiologic hypothermia of newborn kittens up to 6 weeks old]. AB - Kittens showed a physiological hypothermia until they were 6 weeks of age. In the first 3 weeks of age rectal temperature was constantly low (37.6 +/- 0.3 degrees C). A linear increase of rectal temperature followed from the fourth to the sixth week of age inclusively and from the seventh week on rectal temperature reached the final temperature level (38.4 +/- 0.3 degrees C). This finding has to be considered in clinical assessment of kittens' body temperature. PMID- 8212953 TI - Bone lesions of multiple myeloma in three dogs. AB - Three cases of canine multiple myeloma that showed monoclonal IgA gammopathy and bone lesions were examined. One dog was associated with Bence-Jones proteinuria as well. Radiographic examination revealed extensive skeletal involvement of flat bones such as scapula, pelvic bone, costa, and epiphysis of long bones where the hematopoiesis was active throughout the life. Histopathologically, small osteolytic lesions occurred from periosteum and Haversian canal as well as endosteum, and larger lesions were formed by gradual expansion or fusion of small lesions. Osteolytic lesions did not necessarily involve tumor growth, explaining the inconsistent confirmation of tumor cells in biopsy specimens for diagnosis of multiple myeloma and suggesting the possible mechanism for osteolysis by some other humoral factors. PMID- 8212955 TI - Observation of duodenal bile shuttle in the sheep. AB - Relation between duodenal anatomy and function was studied in cannulated sheep. It was concluded that during the interperistaltic periods, gravitational backflow of bile and admixed pancreatic juice towards the pylorus may provide a means for desorption of enterokinase from the mucosal surface of the cranial duodenum. The biliary back and forth ("bile shuttle") may contribute to the utilization of duodenal enterokinase. PMID- 8212956 TI - The response of plant NAD+ kinase to abiotic stresses. PMID- 8212957 TI - Is the 65 kDa protein a direct signal for the nuclease release from nuclear matrix, starting the apoptotic cascade? PMID- 8212958 TI - Electrochemical reduction products of azido nucleosides, including zidovudine (AZT): mechanisms and relevance to their intracellular metabolism. AB - Previous studies on electrochemical reduction of the HIV reverse transcriptase inhibitor, 3'-azido-3'-deoxythymidine (Zidovudine, AZT) and several of its analogues, have been extended to 2'-AZdT and two of the intracellular metabolites of AZT, the 5'-O-glucuronide (GAZT) and the 5'-phosphate (AZTMP). Also investigated were azido nucleosides with aglycons susceptible to electrochemical reduction, cytosine and adenine. The surface activities of these compounds at the mercury electrode were examined. In all instances, reduction of the azido group was a two-electron process, with conversion to an amino group. For an azido adenine nucleoside, it proved possible to reduce the azido group without affecting the aglycon. Electrochemical reduction is shown to provide a simple one step synthesis of amino nucleosides from the available azido nucleosides. The reduced compounds, several hitherto unknown, are useful reference standards for following intracellular metabolism of azido nucleosides, and may also prove of interest as new potential antimetabolites. PMID- 8212959 TI - Isolation and properties of the subunit form EF-1C of elongation factor 1 from Guerin epithelioma cells. AB - EF-1C is a component of the aggregate EF-1B, consisting of the subunit forms EF 1A.EF-1C; it was isolated by dissociation of this aggregate in the presence of GTP. The subunit form EF-1C stimulates binding of aminoacyl-tRNA to ribosomes, catalysed by EF-1A, similarly as EF-1 beta gamma which stimulates the activity of EF-1 in other eukaryotic cells. EF-1C in the presence of 6 M urea was separated into two polypeptides. Polypeptide of molecular mass 32,000 Da is responsible for regeneration of the EF-1A.GTP active complex. Thermal sensitivity of EF-1A was much higher than that of EF-1B, thus a protective role of EF-1C in the EF-1A.EF 1C complex is suggested. PMID- 8212960 TI - Comparative studies on fish and bird insulin receptors. AB - The comparative studies were performed on insulin receptors of erythrocytes and liver plasma membranes in fish (tench and carp) and bird (duck). The Scatchard plots indicated the presence of two pools of binding sites both in fish and duck. These pools show inter-species differences in binding ability and the number of receptors. Specific binding of insulin and the binding affinity are higher in duck than in fish. PMID- 8212961 TI - Iodine induced alteration in immunological and biochemical properties of thyroglobulin. AB - The influence of iodine-iodide solution on the biochemical and immunological properties of human thyroglobulin (hTg) were studied. Human Tg preincubated with the iodine-iodide solution is split to small molecular mass fragments after disulphide bridge reduction with dithiothreitol. The peptide bond cleavage by iodine pretreatment and reduction is possibly linked with the coupling reaction of diiodotyrosyl residues. Pretreatment of hTg with iodine-iodide solution at 1 10 microM decreased the binding of autoantibodies to hTg. The iodine-iodide induced inactivation of hTg autoepitopes is pH dependent and is possibly caused by iodination of tyrosyl residues present in the epitope structure. PMID- 8212962 TI - Continuous recording of intramitochondrial pH with fluorescent pH indicators: novel probes and limitations of the method. AB - In addition to 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) used so far to monitor intramitochondrial pH, two other fluorescent pH indicators, 4',5' dimethyl-5(6)-carboxyfluorescein (DMCF) and carboxyseminaphthofluorescein (carboxy-SNAFL-1), were applied for this purpose. These probes are taken up by isolated rat liver mitochondria in form of diacetate esters, hydrolyzed within mitochondria to free acids, and respond to changes of intramitochondrial pH by changing their fluorescence emission intensity. With all three probes energization of mitochondria by electron donors or acceptors was accompanied by fluorescence changes characteristic for alkalization, whereas deenergization by respiratory inhibitors or protonophores produced changes typical for acidification. Contrary to this, transition from State 4 to State 3, known to shift intramitochondrial pH towards acidification (equivalent to a decrease of delta pH), was accompanied by paradoxical responses of the fluorescent pH probes used: the fluorescence of DMCF increased as if the matrix compartment became more alkaline, the fluorescence of BCECF, measured in single excitation/emission wavelength mode, did not change, and the fluorescence of carboxy-SNAFL-1 could be interpreted as either alkalization or acidification, depending on the excitation/emission wavelength pair used. It was shown that depletion of intramitochondrial Mg2+ and Ca2+ using divalent metal ionophore A23187 decreased fluorescence intensity with all three probes examined, whereas subsequent addition of Mg2+ or Ca2+ increased the fluorescence. It is therefore proposed that the atypical response of intramitochondrial pH indicators upon State 4- State 3 transition is due to changes of intramitochondrial free Mg2+, as related to different complexing abilities of ATP and ADP towards magnesium. PMID- 8212963 TI - Cyclic phosphates of some antiviral acyclonucleosides: relationship between conformation and substrate/inhibitor properties in some enzyme systems. AB - Solution conformations, and substrate/inhibitor properties towards several phosphodiesterases and other nucleolytic enzymes, have been investigated for the cyclic phosphates of various acyclonucleosides, some with known antiviral activity, including 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG) and its carbocyclic congener, 9-(3,4-dihydroxybutyl)guanine (DHBG),9-[4-hydroxy-2 (hydroxymethyl)- butyl]-guanine (2HM-HBG), and 9-(2,3-dihydroxypropyl)guanine (HPG). Conformations of the cyclic phosphate rings were derived from analysis of the 1H-1H and 1H-31P vicinal coupling constants in the 1H n.m.r. spectra, subsequently optimalized by minimalization of the internal energy. The resulting structures were examined with respect to their ability to recognize various specific phosphodiesterases and nucleases, and some structural parameters were delineated for acyclonucleotide interactions. Qualitative data are presented for inhibitory properties of the acyclonucleoside cyclic phosphates, and, in those instances where they were substrates, kinetic constants were evaluated. An unusual finding was the apparent ability of nuclease P1 to hydrolyse a five membered cyclic phosphate ring of an acyclonucleoside. PMID- 8212964 TI - Comparison of pyruvate kinase variants from rat liver and Morris hepatoma 7777, obtained by an affinity chromatography on blue sepharose CL-6B. AB - Fractions A (salted out by ammonium sulphate between 21-30% saturation), and fractions B (salted out between 51-70% saturation) of pyruvate kinase (EC 2.7.1.40.) corresponding respectively to pyruvate kinase types L and M2 from rat liver and Morris hepatoma 7777 were purified by an affinity chromatography on Blue Sepharose CL-6B. Peaks of inactive proteins were eliminated and the enzyme fractions bound biospecifically to the gels were eluted by free ADP. The molecular mass of purified hepatoma pyruvate kinase fraction B was smaller than that of liver pyruvate kinase fraction B. Morris hepatoma pyruvate kinase fraction B represented a variant of type M2, characterised by greatest affinity to 2-phosphoenolpyruvate as a main substrate and different sensitivity to low molecular effectors in comparison with types L from both liver and hepatoma and in comparison with type M2 from normal rat liver. Only this hepatoma fraction B showed a tumour specific sensitivity to L-cysteine and was insensitive to normal signal molecules i.e. to ATP and fructose-1,6-diphosphate which influence liver pyruvate kinase activity. L-Cysteine inhibited the tumour fraction B of pyruvate kinase by decreasing its Vmax and increasing the Km values in relation to 2 phosphoenolpyruvate. PMID- 8212965 TI - The impaired transcription factor AP-1 DNA binding activity in lymphocytes derived from subjects with some symptoms of premature aging. AB - The study of human disorders known as premature aging syndromes may provide insight into the mechanisms of cellular senescence. The main feature of cellular senescence in vitro is cessation of cell proliferation. Down syndrome (DS) and neuronal ceroid-lypofuscinosis (NCL) are clinically characterized by the premature onset of numerous features normally associated with human aging. Phytohemagglutinin stimulated lymphocytes derived from DS subjects showed a statistically significant diminished proliferation capacity in comparison with lymphocytes derived from NCL and healthy individuals. We demonstrated, by applying the electrophoretic mobility shift assay, slightly impaired AP-1 DNA binding activity in NCL lymphocytes and strong in DS ones. Our results showed that the same molecular mechanisms of proliferation cessation could exist in fibroblasts characterized by replicative senescence and in lymphocytes derived from individuals with premature aging syndromes (Down). PMID- 8212966 TI - Expression of genes 51, 27, 28 coding for proteins of the central part of bacteriophage T4 baseplate in the bacteriophage T7 promoter/RNA polymerase expression system. AB - A fragment of T4 DNA (XbaI-HindIII) comprising the genes 51, 27, 28, which encodes the central plug proteins was cloned into plasmid pT7-5 and p7-6 (T7 RNA polymerase expressing system). The examined genes were only overexpressed when the orientation of cloned DNA to promoter phi 10 was as follows: promoter phi 10 and genes 51, 27, 28. This was achieved when the fragment (XbaI-HindIII) was cloned into plasmid pT7-5. Gene 27 and 28 were overexpressed when the intact fragment (XbaI-HindIII) was used. The high rate of the synthesis of proteins 27 and/or 28 had a strong inhibitory effect on the level of synthesis of the product of gene 51. For the overexpression of gene 51 in this system a deletion derivate which was devoid of gene 28 and a larger fragment of gene 27 was prepared. PMID- 8212967 TI - Phonocardiography: past, present and future. PMID- 8212968 TI - Does aortic regurgitation affect transmitral flow? An echo-Doppler study. AB - Recent studies suggest that the presence of aortic regurgitation can interfere with Doppler measurement of mitral pressure half-time in patients with mitral stenosis. Amongst the factors affecting the transmitral flow in aortic regurgitation a putative role may be played by the mechanical hit of the aortic regurgitant jet impinging on the anterior mitral leaflet, as is very often seen with Doppler Color Flow examination. This study was designed to evaluate the effects of pure aortic regurgitation on the transmitral flow in patients with normal mitral valves. We studied 35 patients affected by pure chronic aortic regurgitation but with a normal mitral valve and compared them with 30 normal subjects. In all the patients the aortic regurgitant jet was directed toward the anterior mitral leaflet. In all the patients and control subjects a standard echo Doppler examination was performed, sampling the transmitral flow at the level of the tip of the mitral leaflets. In 7 patients and 11 normal subjects the transmitral flow was also sampled at the level of the mitral annulus. Patients with aortic regurgitation showed significantly higher values of the mitral pressure half-time (61.04 +/- 15.14 vs 50.59 +/- 7.07 ms, P < 0.05) and of the time-velocity integral of the total transmitral flow, while the other parameters of transmitral flow, the mitral annulus diameter and the mitral stroke volume didn't show statistically significant differences. The comparison of the pressure half-time and time-velocity flow values measured at the level of the mitral annulus between patients and normal subjects didn't show significant differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212969 TI - On the relationship between nutrition, sex hormones and high-density lipoproteins in women. AB - Western women have significantly higher high-density lipoprotein (HDL) cholesterol levels than Oriental women whereas in men HDL-cholesterol levels are very similar. Oriental women have HDL-cholesterol levels similar to those of both Western and Oriental men. Western women show a markedly higher resistance against atheromatous diseases than men. Evidence is provided demonstrating that women are able to increase their HDL-cholesterol levels on a nutrition high in saturated and monounsaturated fat. This could be explained by a concurrent dietary fat related increase in female sex hormone levels (e.g. estradiol and estrone), hormones which are known to increase HDL-cholesterol levels. PMID- 8212970 TI - Membranous subvalvular pulmonary stenosis in complete transposition of the great arteries: usefulness of serial exercise testing. AB - A 22-year-old male who had Mustard repair for complete transposition presented with progressive exercise intolerance, documented by a gradual decrease in exercise capacity on cycle ergometer. Cardiac catheterization and angiography demonstrated subvalvular pulmonary stenosis. After surgical relief of the obstruction, exercise capacity returned to previous level. PMID- 8212971 TI - Apical hypertrophic cardiomyopathy. AB - Illustrated by a case report, which was rather suggestive of coronary ischemic heart disease, the principle characteristics of apical hypertrophic cardiomyopathy are outlined. Outside East Asia, it remains a very uncommon variant of hypertrophic cardiomyopathy. The electrocardiogram in basal conditions showed giant negative T-waves (-14 mm) in the precordial leads, while the ventriculogram in RAO projection revealed the typical, so called "ace of spades" configuration. Based on the present literature and the follow-up of these patients a review of apical hypertrophic cardiomyopathy is presented. One of the most important consequences of the identification of this variant seems to be the rather good prognosis when compared to other forms of hypertrophic cardiomyopathy. PMID- 8212972 TI - Early detection of left ventricular aneurysm rupture by two-dimensional echocardiography and surgical salvage. AB - A 52-year-old man was admitted to hospital emergency room with cardiogenic shock. The electrocardiogram showed normal tracing. Left ventricular aneurysm rupture at the posterolateral wall and haemopericardium was diagnosed with two-dimensional and colour Doppler echocardiography. The patient was operated on immediately and the defect was repaired. The patient made a good recovery. Four months later coronary angiography and left ventriculography were performed. The coronary vessels were found patent and there was minimal stenosis (lesser than 50%) at the proximal 1/3 portion of left anterior descending (LAD) artery. Left ventriculography showed anterolateral and posterolateral hypokinesis. The patient was symptom free and leading an active life 4 months later. PMID- 8212973 TI - Some thoughts on the treatment of non-insulin-dependent diabetes mellitus. PMID- 8212974 TI - Stereotactic radiosurgery of cerebral metastases: preliminary results. AB - The authors have treated 11 solitary cerebral metastases in 9 patients with stereotactic radiosurgery. This relatively new technique of stereotactic single high dose radiotherapy (15-30 Gy to the 70% isodose) is explained. All metastases responded to treatment: six disappeared on CT scan, while the volume of the remaining five diminished significantly. All patients with neurological symptoms had a satisfactory recuperation. There were no complications inherent to the technique. The indications and advantages of this innovative form of "surgical" radiotherapy are discussed. PMID- 8212975 TI - Importance of weight loss and sodium restriction in the treatment of mild and moderate essential hypertension. AB - The effectiveness of non pharmacological treatment of chronic arterial hypertension has been evaluated in 116 treated or not primary hypertensive out patients. Those receiving diuretics were however excluded. This population was requested to follow for 3 months a modification of their usual diet characterized by salt restriction combined with energy intake restriction when the patients were above their ideal body weight. Only 62 patients (53%) completed the study. However, this approach was effective by decreasing blood pressure and total cholesterol. The weight loss appears the most effective way to decrease blood pressure in untreated patients, but needs 3 months to be significant. In drug treated patients, the sodium restriction significantly influences the blood pressure level, already after 1 month. However, salt sensitivity has been noted, especially in the most severe forms of the hypertensive disease. The combination of both modifications (weight loss and sodium restriction) does not appear to be more effective than each separate dietary measure. PMID- 8212976 TI - Hepatic artery aneurysm. Case reports with review of the literature. AB - Two cases of hepatic artery aneurysm are reported. The first presented as obstructive jaundice, the second as an upper gastrointestinal bleeding. The diagnosis was made by performing ultrasound, CT-scan and angiography. In both cases surgery was the treatment. However, in some cases, interventional angiography with embolisation of the affected vessel offers an alternative treatment. PMID- 8212977 TI - Early complications of radioiodine treatment for hyperthyroidism. AB - Three patients were described with undesirable early complications of low dose radioiodine treatment for hyperthyroidism. The first patient with Graves' disease developed an extreme and permanent hypothyroidism within only few months after receiving this therapy. The second patient with a hyperactive nodular goiter and mild hyperthyroidism had an immediate important exacerbation of the symptoms of hyperthyroidism shortly after a low dose treatment. In the third patient with Graves' disease but without preexisting eye disease a therapy-resistant endocrine ophthalmopathy occurred two months after radioiodine administration. PMID- 8212978 TI - Combination of oral antidiabetic drugs and insulin in the treatment of non insulin-dependent diabetes. AB - Non-insulin-dependent diabetes mellitus (NIDDM) appears to be an heterogeneous disorder characterized by both relative insulin deficiency and impaired insulin action. The initial management of NIDDM should include patient education, dietary counselling and individualized programs of physical activity. It is only when such measures fail that drug therapy should be considered. Oral drug therapies include sulphonylurea derivatives, biguanides, among which metformin remains the only one commercialized in our country, and alpha-glucosidase inhibitors such as acarbose. However, insulin therapy may be required to achieve adequate glycaemic control in some patients, the so-called secondary failures to oral treatment. The rationale for combining insulin and oral drug therapy derives from a better understanding of the pathophysiology of NIDDM and of the mechanisms of action of the oral drugs available: 1) type 2 diabetic patients are both insulin-deficient and insulin-resistant, thus requiring quite high doses of exogenous insulin; 2) peripheral insulin delivery leads to hyperinsulinaemia which could play a role in the pathogenesis of late diabetic complications; 3) sulphonylureas stimulate insulin release directly into the portal vein and could also potentiate peripheral insulin action; and 4) metformin (by improving glucose metabolism and insulin sensitivity) and alpha-glucosidase inhibitors (by slowing down the digestion of complex carbohydrates and sucrose) are able to reduce the amounts of insulin needed to control postprandial hyperglycaemia. Numerous studies have shown that a combination of insulin and sulphonylurea is more effective than insulin alone in the treatment of patients with NIDDM after secondary failure to oral drugs, leading to better glucose profiles and/or decreased insulin needs. The available data suggest that combination therapy is most beneficial in the diabetic patient who still has residual insulin secretory capacity and that the best scheme comprises an evening injection of lente insulin and the administration of sulphonylureas before meals. Preliminary results suggested that insulin-metformin (when obesity is present) or insulin-acarbose (when post prandial hyperglycaemia occurs) combinations might offer some favourable features for the treatment of NIDDM patients although these therapeutical approaches still require adequate evaluation in further controlled studies. The additional cost of such combined therapy should be weighed against the potential advantages of better metabolic control. PMID- 8212979 TI - [Alcohol, liver cirrhosis and disorders in sex hormone metabolism]. AB - Abnormalities in the metabolism of sex hormones are frequently observed in cirrhotic patients, especially in chronic alcoholics. Signs of hypogonadism with disturbed reproductive and endocrine gonadal functions are found in men as well as in women. Primary hypogonadism as well as hypothalamic-pituitary inhibition seem to play a role. Primary gonadal insufficiency is the result of a direct toxic effect of ethanol and of acetaldehyde on the gonads with inhibition of LH binding to the Leydig cells, with inhibition of the enzymes responsible for the formation of sex hormones, and with inhibition of the intratesticular activation of vitamin A. Hypothalamic-pituitary hypogonadism also results from a direct toxic effect of ethanol as well as from the increasing concentrations of oestrogens in the plasma. Men with alcoholic cirrhosis may also be characterized by signs of feminization, which mainly result from an increased peripheral conversion of androgens. In men who abstain from alcohol, a spontaneous recovery of sexual functions can occur, especially when no testicular atrophy is found and when the response of gonadotrophins after stimulation with LH-RH is normal. Therapeutically, only the administration of non-aromatizable androgens in high doses seems to lead to recovery of potency. PMID- 8212980 TI - Drugs recently released in Belgium. Cefpodoxime proxetil--Fosinopril. PMID- 8212981 TI - Growth hormone "replacement" therapy--clues and claims. PMID- 8212982 TI - Life with Turner's syndrome--a psychosocial report from 22 middle-aged women. AB - Twenty-two middle-aged women (median age 44.5 years) with Turner's syndrome were interviewed about family background, social identity, emotional development, relations, female identity, sexuality and reactions to the diagnosis, to evaluate how the condition has affected their lives and coping style. During the years preceding the diagnosis and hormonal replacement therapy (HRT) they had often isolated themselves as they felt different from their peers. Ovarian failure and infertility, not the body height, were the major problems for most of the women. Infertility had affected the women very deeply and many felt depressed because of this. Adolescent behaviour, a feeling of chronic inferiority or a feeling of grief were different ways of coping with the situation. Median age at sexual debut was 19.5 years. Painful intercourse related to vaginal constriction and sore membranes was commonly reported. Most of the women had stopped HRT because of side-effects. Many of the problems experienced by the women could have been avoided if proper HRT had been administered in due time and on a long-term basis. This emphasizes the importance of regular contact with a gynecologist of special training and interest. PMID- 8212983 TI - Cardiovascular risk factors in adult patients with growth hormone deficiency. AB - Patients with adult onset growth hormone deficiency have a decreased life expectancy owing to an increased mortality from cardiovascular disease. In the present study, 104 subjects (66 men and 38 women, aged 22-74 years) with growth hormone deficiency and with adequate replacement therapy with glucocorticoids, thyroid hormones and gonadal steroids were studied with respect to known risk factors for cardiovascular disease. For comparison, data from a population study, "the MONICA study", were obtained. The patients had a significantly higher body mass index compared to controls (p < 0.001). Serum triglyceride concentration was higher (p < 0.001) but there was no difference in serum total cholesterol concentration. Serum high-density lipoprotein cholesterol concentration was lower (p < 0.001) in the patients. There was no difference in the prevalence of diabetes mellitus. The prevalence of treated hypertension was higher (p < 0.05) in the patients but the prevalence of smoking was lower (p < 0.001). Even after taking the increased body mass index into consideration, the changes in the prevalence of treated hypertension (p < 0.05) and in the serum concentrations of triglycerides (p < 0.05) and high-density lipoprotein concentrations (p < 0.001) remained. These results indicate that growth hormone deficiency alters lipoprotein metabolism and increases the risk for development of hypertension, which in turn might contribute to the increased risk for cardiovascular disease. PMID- 8212984 TI - Reduced bone mineral content in adult patients with growth hormone deficiency. AB - Bone mineral content was measured in a follow-up study of adult patients with hypopituitarism and growth hormone deficiency. There were 95 patients (59 males, mean age 54.0 years, range 21-74 years; 36 females, mean age 53.5 years, range 31 73 years). Routine replacement therapy with cortisone acetate and L-thyroxine was given. All males that were gonadal deficient were on proper testosterone therapy, except in four patients who were treated separately. Bone mineral content (g/cm) was measured using dual-photon absorptiometry in the third lumbar vertebra. Bone mineral content in the patients was compared with a control population (N = 413, 25-74 years of age). Bone mineral content was significantly lower in males (N = 55, p < 0.05) compared with controls. In females, bone mineral content was significantly lower both among the subjects with untreated gonadal deficiency (p < 0.001) and among those with treated gonadal deficiency and normal premenopausal gonadal function (p < 0.005) compared with controls. To summarize, patients with hypopituitarism on routine replacement therapy but not growth hormone have a lower bone mineral content than the controls. The reduced bone mineral content might be a result of untreated growth hormone deficiency. PMID- 8212985 TI - Restoration of gallbladder contractility after withdrawal of long-term octreotide therapy in acromegalic patients. AB - We sought to examine how the discontinuation of octreotide in long-term octreotide-treated acromegalic patients affects the well-documented side-effect of cholelithiasis. In 14 acromegalic patients, serum growth hormone levels, insulin-like growth factor I levels and percentage of relative gallbladder contractility were measured prior to and after the discontinuation of octreotide. Compared to pretreatment values, the basal growth hormone and 5-h growth hormone profiles were 36% and 24%, and 60% and 56% at the end of 1 and 2 weeks, respectively. Octreotide was found to be eliminated completely from the serum within 3 days after its withdrawal. In all of six patients who did not develop gallstones, the percentage relative gallbladder contractility normalized within 1 week. In eight patients who developed gallstones, four of them had restoration of normal contractility within 2 weeks. Our results show that upon withdrawal of octreotide, gallbladder contractility returns to normal while growth hormone suppression persists for a longer period of time. Therefore, discontinuation of octreotide therapy may allow for the clearance of stagnated bile and hence decrease the incidence of cholelithiasis in acromegalic patients receiving long term therapy. PMID- 8212986 TI - Interleukin 8 concentrations in amniotic fluid and peripheral venous plasma during human pregnancy and parturition. AB - To establish the gestational and labour-associated changes in interleukin 8 (IL 8) release, we have determined the concentration of this cytokine in maternal peripheral plasma and amniotic fluid from 15 weeks of gestation to term and in association with spontaneous-onset labour at term and preterm. No statistically significant changes in peripheral plasma IL-8 concentration were observed during pregnancy or in association with labour onset (mean concentration 56.5 +/- 14.5 ng/l, N = 64). The IL-8 concentrations in amniotic fluid were up to 50-fold greater than those observed in peripheral plasma (p < 0.05) and increased significantly (p < 0.05) during pregnancy. At term, but before the onset of labour, amniotic fluid concentrations of IL-8 averaged 969.2 +/- 553.5 ng/l (N = 12). In association with labour at term, IL-8 concentrations increased to 3895.8 +/- 1414.4 ng/l (N = 6, p < 0.03). The concentration of IL-8 in amniotic fluid obtained from women in preterm labour averaged 1854.7 +/- 1352.6 ng/l (N = 6) but was not statistically different from the concentration of IL-8 in amniotic fluid obtained from gestational aged-matched non-labouring controls. Although the precise role of intrauterine IL-8 at the time of parturition awaits elucidation, these data support the concept that this cytokine may be involved in the biochemical events associated with the onset and/or propagation of normal labour in the human. PMID- 8212987 TI - Lipoprotein(a) and postmenopausal oestrogen. AB - Epidemiological studies have shown that postmenopausal oestrogen therapy substantially reduces the risk of cardiovascular and cerebrovascular disease and this is partly mediated by oestrogen-associated changes in lipoproteins, particularly high-density lipoprotein. In this study, we investigated whether changes in lipoprotein(a) might help to account for the reduction in coronary heart disease and stroke associated with postmenopausal oestrogen therapy. The study group consisted of 18 women who had hysterectomy and bilateral oophorectomy at least 2 months prior to recruitment and had received no previous hormonal therapy. Serum samples were collected for measurement of lipoprotein(a) before and after 4 months of treatment with oestradiol valerate (2 mg/day). Lipoprotein(a) levels ranged from 35 to 720 mg/l (median 180 mg/l) before treatment and from 55 to 780 mg/l (median 130 mg/l) after oestradiol treatment and showed no consistent pattern of change. It would appear, therefore, that treatment with unopposed oestrogen in relatively low doses not have a marked effect on lipoprotein(a), at least in the short term. PMID- 8212988 TI - Pulsatile luteinizing hormone secretion during the first and the fourth cycle on two different oral contraceptives containing gestodene. AB - Oral contraceptives inhibit ovarian follicular growth by suppressing the release of gonadotropins from the pituitary. We studied basal and gonadotropin-releasing hormone-stimulated gonadotropin release, as well as pulsatile luteinizing hormone (LH) secretion, in ten healthy volunteers who had not used oral contraceptives before. Subjects received either a monophasic preparation containing 30 micrograms of ethinylestradiol and 75 micrograms of gestodene (group 1) or a triphasic formulation containing 30-40 micrograms of ethinylestradiol and 50, 70 and 100 micrograms of gestodene (group 2). Blood sampling at 10-min intervals during 6-h periods was performed on days 1, 8, 15 and 21 of both the first and fourth pill cycle. Thirteen healthy volunteers with regular ovulatory cycles served as normal controls. Both LH and follicle-stimulating hormone (FSH) were measured by a sensitive immunoradiometric assay. Pulsatile LH secretion was observed in all oral contraceptive users. Mean serum LH and FSH levels, number of pulses/6 h and the amplitude of LH pulses on day 1 in both the first and fourth pill cycle did not differ from early follicular phase controls in both groups. The FSH levels were suppressed rapidly in both groups, even in first cycles, while LH serum levels progressively declined in all cycles studied. In both groups, amplitudes of LH pulses decreased from day 8 onwards, with a substantial number of low-amplitude pulses (< 0.75 U/l) interspersed between large-amplitude pulses. On day 1 of the fourth pill cycle a significant number of pulses were of low amplitude.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212989 TI - Endocrine and morphological features of cystic ovarian condition in antiprogesterone RU486-treated rats. AB - Four-day cyclic Wistar rats (200 g body wt) were injected (sc) with the antiprogestagen RU486 (4 mg RU486/0.2 ml oil) on estrus, metestrus, diestrus and proestrus. Groups of rats (12-15) were decapitated on days 1 (day of expected ovulation), 5, 9, 13, 17 and 21 after the 4 days of RU486 treatment. Oil-injected rats decapitated on proestrus (day 0) and estrus (day 1) served as controls. In both controls and RU486-treated rats, the following parameters were noted: ovulation, vaginal smears and luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, testosterone and estradiol-17 beta serum concentrations. Also, pituitary, adrenal, uterus and ovary weight were recorded. RU486 induced ovulation blockade, persistent vaginal cornification, uterine ballooning and increased serum levels of LH, FSH, prolactin, testosterone and estradiol. Furthermore, the LH/FSH and testosterone/estradiol ratios in serum increased. Pituitary and ovary weights also increased. The enlarged ovaries showed follicular cysts undergoing atresia and/or different degrees of luteinization of granulosa cells resembling, in some cases, genuine corpus luteum containing the ovocyte. The small follicles showed extensive atresia and stimulated thecal cells. These effects are reversible and remain in a stationary state for about 9-13 days after RU486 treatment. While the endocrinological alterations found in rats treated with RU486 are similar to those exhibited in polycystic ovarian disease, the morphological alterations found in the ovaries seem to be more closely related to the multicystic ovarian condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212990 TI - Demonstration of biological activity of a growth hormone-releasing hormone-like substance produced by a pheochromocytoma. AB - The biological characteristics of a growth hormone-releasing hormone (GHRH)-like substance produced by a pheochromocytoma were studied. Analysis by gel filtration chromatography combined with the use of two distinct GHRH antisera that recognize the N- and C-termini of authentic GHRH(1-44)NH2 indicated molecular heterogeneity of the immunoreactive GHRH in the tumor extract, but a component corresponding to GHRH(1-44)NH2 was the predominant form. The biological activity of this immunoreactive component was assessed in vitro by measuring its ability to induce growth hormone release from dispersed rat anterior pituitary cells. At concentrations of 0.125-2.0 nmol/l, the test materials induced a dose-related increase in growth hormone release from the cells into the incubation medium (range 992 +/- 68-1872 +/- 32 ng.1.7 x 10(5) cells-1 x 3 h-1), similar to that observed with synthetic GHRH(1-44)NH2. (control value 640 +/- 30 ng.1.7 x 10(5) cells-1 x 3 h-1). This suggests that immunoreactive GHRH in the tumor has almost the same biological activity as the synthetic product and that a combination of pheochromocytoma and acromegaly is not always fortuitous because both diseases may be caused by a single neoplasm. PMID- 8212992 TI - Effect of triptorelin (Decapeptyl) combined with heparin on estradiol levels in MCF-7 mammary cancer cells after incubation with estrone sulfate. AB - The effects of triptorelin (Decapeptyl) and heparin, alone or in combination, on the intracellular concentration of estradiol (E2) after incubation of estrone sulfate (E1S) with the MCF-7 mammary cancer cells was investigated. Although heparin (10 mg/l culture medium) or Decapeptyl (5 x 10(-7) or 5 x 10(-5) mol/l) did not affect the levels of radioactive E2 after incubation with [3H]E1S, the combination of Decapeptyl and heparin significantly decreased the radioactive uptake and the intracellular concentrations of [3H]E2. In the absence of Decapeptyl and heparin incubations with E1S, the resulting E2 concentration (in nmol/kg DNA +/- SD) was 558 +/- 44; after heparin (10 mg/l) plus Decapeptyl (5 x 10(-7) or 5 x 10(-5) mol/l) the values were 389 +/- 55 and 165 +/- 18, respectively. It is concluded that Decapeptyl with heparin can decrease very significantly the conversion of E1S to E2 in MCF-7 cells, an observation that suggests new possibilities for the control of E2 in hormone-dependent breast cancer. PMID- 8212991 TI - Pituitary-gonadal function in neonatal and adult female rats treated with gonadotropin-releasing hormone agonist and antagonist: short- and long-term effects. AB - We have analyzed the mechanisms involved in ovarian failure after administration of gonadotropin hormone-releasing hormone agonists (GnRH-A) or antagonists (GnRH ANT). Ovarian and uterine weights, serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol and pituitary FSH and LH contents were measured in Wistar female rats injected from 1-15 or 90-104 days of age with the agonist D-Ala6-D-Gly10-GnRH or the GnRH-ANT Org. 30276. Vaginal opening, first estrous presentation, vaginal smears and reproductive capacity were also analyzed. In both neonatal and adult females GnRH-A induced pituitary desensitization and reduced ovarian and uterine weights and estradiol serum concentrations. Therefore, serum gonadotropin concentrations were increased in adults and decreased in neonatal females. Puberty occurrence and reproductive function remain unaltered after neonatal treatment with GnRH-A. In neonatal females, FSH and LH pituitary content and FSH serum concentrations decreased at the end of treatment with GnRH-ANT. The effects on LH and estradiol secretion depended on the pattern of treatment. Interestingly enough, both vaginal opening and first estrous presentation were precipitated by GnRH-ANT administration. Normal reproductive function was observed in adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8212993 TI - Proopiomelanocortin, prolactin and growth hormone messenger ribonucleic acid levels in the fetal sheep pituitary during late gestation. AB - We have measured the relative levels of proopiomelanocortin (POMC), prolactin (PRL) and growth hormone (GH) messenger ribonucleic acid (mRNA) in the anterior and neurointermediate lobes of the fetal pituitary during the last 2-3 weeks of gestation. The mean POMC mRNA/18S RNA ratio in the fetal anterior pituitary was significantly greater (p < 0.02) at 130-136 days (0.90 +/- 0.08; N = 9) than at 141-143 days of gestation (0.67 +/- 0.07; N = 6). In contrast, the mean PRL mRNA/18S RNA ratio increased significantly (p < 0.02) between 130 and 136 days (0.31 +/- 0.05; N = 9) when compared with 141-143 days of gestation (0.58 +/- 0.10; N = 6). There was no significant difference, however, between the mean GH mRNA/18S RNA ratio in fetal anterior pituitaries at 130-136 days (0.95 +/- 0.04; N = 9) when compared with 141-143 days of gestation (1.08 +/- 0.14; N = 6). The POMC mRNA/18S RNA ratio in the neurointermediate lobes was seven-, five- and tenfold higher than anterior pituitaries at 130-134, 135-136 and 141-143 days of gestation, respectively. We hypothesize that elevated circulating cortisol levels after 140 days of gestation act in the slow time domain (i.e. over days) to suppress POMC gene expression and that the increase in fetal pituitary PRL mRNA levels may be a consequence of oestrogen stimulation in late gestation. PMID- 8212994 TI - Intraventricular injection of agents that enhance cyclic adenosine monophosphate formation leads to inhibition of proestrous luteinizing hormone surge in rats. AB - The effect of increasing hypothalamic levels of 3',5'-cyclic adenosine monophosphate (cAMP) on the preovulatory surge of luteinizing hormone (LH) and ovulation was studied in cycling rats. Animals hearing chronically implanted guiding cannulae into the third ventricle were injected with agents known to enhance the cellular levels of cAMP. Hourly blood samples from the unanesthetized, unrestrained rats were obtained between 11.00 and 17.00 h through a plastic cannula inserted into the jugular vein. Intraventricular injections of serotonin (7.5 mg/ml; 2 microliters) in the morning of proestrous blocked the preovulatory surge of LH and ovulation. This effect was assigned to an increased neuronal level of cAMP because it was prevented by a serum anti-cAMP. Third ventricle injections of 2 microliters of forskolin (0.5 mmol/l), guanosine 5'-O (3-thiotriphosphate)(2 mmol/l) or dibutyryl-cAMP (1 mmol/l) at 11.00 h on the day of proestrus mimicked the inhibitory effect of serotonin on the proestrous release of LH. It is suggested that serotonin inhibits LH surge by acting directly on LH-releasing hormone neurons and/or on neurons that provide inputs to these neurons involving cAMP as a second messenger. Neurons releasing gamma aminobutyric acid (GABA) may serve as interneurons sensitive to serotonin, as well as to cAMP, inasmuch as the inhibitory effect of forskolin on the release of LH was partially blocked by the GABA antagonists, picrotoxin and bicuculline. PMID- 8212995 TI - Comment on the variable functional consequences of compound heterozygous mutations in the CYP17 gene. PMID- 8212996 TI - Use of the erythrogram in the diagnosis of iron deficiency in elderly patients. AB - In elderly patients the diagnosis of iron deficiency from full blood count indices is often difficult. We assessed an automated technique (numerical data of the erythrogram; Technicon H*1) by which the proportions of microcytic (< 60 fl) and/or hypochromic (< 28 g.dl-1) red blood cells are determined. Of 472 elderly patients investigated, 100 (21%) were found to have iron deficiency (plasma ferritin < or = 45 ng.ml-1). Less than two-thirds of patients with iron-deficient erythropoiesis (anaemia or microcytosis) had increased proportions of hypochromic and/or microcytic red blood cells. Furthermore, the erythrogram was not sensitive in detecting latent or early iron deficiency. The erythrogram also lacked specificity for iron deficiency anaemia as many patients with mild normocytic anaemia associated with chronic inflammatory disease had increased proportions of hypochromic and/or microcytic red blood cells. Although patients with iron deficiency had increased proportions of hypochromic normocytic (p < 0.01) and normochromic microcytic red blood cells (p < 0.05) compared to those with chronic inflammatory disease and normal or raised iron stores (ferritin > or = 100 ng.ml 1, n = 32), there was a large overlap between these two groups, and the grossly elevated erythrogram results in patients with iron deficiency were almost always associated with a mean cell volume (MCV) < 80 fl, whereas none of the patients with chronic inflammatory disease and normal or raised iron stores had an MCV < 80 fl. Thus the erythrogram does not appear to be of value in the routine assessment of iron status in elderly patients. PMID- 8212997 TI - Immunological analysis of T cells bearing T cell receptor alpha/beta or gamma/delta in patients with granular lymphocyte proliferative disorder. AB - Immunological analysis of 2 cases of granular lymphocyte proliferative disorder with clonal expansion of CD3+4-8+ T cells bearing either T cell receptor alpha/beta (patient 1) or T cell receptor gamma/delta (patient 2) is reported. Significant cytotoxic activity against K562 was observed in peripheral blood mononuclear cells (PBMC) isolated from patient 2, but not in PBMC from patient 1, although the cytotoxic activity of patient 1 could be augmented following incubation with anti-CD3 monoclonal antibody (MoAb). Northern blot analysis revealed that perforin mRNA was expressed in both patients. Proliferative response to phytohemagglutinin, anti-CD3 MoAb and 12-O-tetradecanoylphorbol-13 acetate was low in PBMC from both patients compared to that from healthy controls. Cytoplasmic free calcium of PBMC from the 2 patients increased similarly to that of healthy controls after treatment with anti-CD3 MoAb. PMID- 8212998 TI - Study of platelet function in patients with sickle cell anemia during steady state and vaso-occlusive crisis. AB - Although there are many reports providing evidence for platelet hyperactivity during acute infarctive crisis in sickle cell disease, little attention has been paid to the study of platelet release reaction in steady state. Plasma levels of the alpha-granule constituents beta-thromboglobulin and platelet factor 4 were measured in patients with sickle cell anemia during steady state and vaso occlusive crisis in order to determine in vivo platelet activity. Significantly higher plasma levels of both proteins were found in steady state and in crisis when compared with those of normal controls. Platelet hyperactivity was also found to be more vigorous in painful crisis, suggesting a possible therapeutic role for drugs that inhibit platelet function. PMID- 8212999 TI - Phase II study of recombinant human granulocyte-macrophage colony-stimulating factor in myelodysplastic syndrome and aplastic anemia. AB - As phase II study, we treated 18 patients with myelodysplastic syndrome (MDS) and 37 patients with aplastic anemia (AA) with recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) for 14-28 days. Administration of rhGM-CSF resulted in a dose-dependent increase in circulating granulocyte counts, which was statistically significant in patients with AA. There were no consistent changes in monocyte and lymphocyte counts. Although no increase in both thrombocyte and erythrocyte counts was detected in the majority of the patients, a response of both lineages to rhGM-CSF, in addition to granulocyte lineage, was observed in 3 patients. Drug-associated adverse events developed in 28 patients (51%). The most frequent adverse event was fever. In general, the treatment with rhGM-CSF was well tolerated. The results suggest that rhGM-CSF is effective for patients with MDS and AA. PMID- 8213000 TI - Method for the direct specific measurement of vitamin B12 bound to transcobalamin II in plasma. AB - The concentration of plasma vitamin B12 bound to transcobalamin II was measured by two methods: QUSO and Heparin Sepharose (HS). The new HS procedure provided a specific, direct measurement of vitamin B12 bound to both R binder and transcobalamin II in plasma. PMID- 8213001 TI - Results of splenectomy for idiopathic thrombocytopenic purpura. Review of 72 cases. AB - Seventy-two patients underwent splenectomy for idiopathic thrombocytopenic purpura between 1979 and 1990. Mean age at splenectomy was 36.4 years (range 11 73). Indications for splenectomy were corticodependence in 21 cases and resistance to steroids in 44 cases. Thirty-five patients had platelet kinetic studies by 51Cr alloplatelets; 22 of them had splenic sequestration. Hematologic results were evaluated on discharge, at 3 months and in the long term (median follow-up 5.4 years). We had no mortality, morbidity was seen in 7% of the cases. None of the patients suffered from secondary infectious complications. 89% had good results on discharge (> 120 x 10(9)/l), 72.6% at 3 months and 90% on long term follow-up. Factors associated with good response to splenectomy included a high postoperative platelet count (more than 120 x 10(9)/l on discharge), younger age at the time of surgery, preoperative corticodependence and predominantly splenic sequestration. PMID- 8213002 TI - Disseminated intravascular coagulopathy caused by acetic acid ingestion. AB - A case of disseminated intravascular coagulopathy following ingestion of 100% acetic acid is presented. The patient was successfully treated with fresh frozen plasma and cryoprecipitate. Complete resolution of the bleeding diathesis and the disturbed coagulation tests was achieved. PMID- 8213003 TI - Protein S deficiency associated to anti-protein S antibodies in a patient with mixed connective-tissue disease and its reversal by danazol. AB - We describe here a female patient with mixed connective tissue disease, secondary antiphospholipid syndrome, pulmonary hypertension and severe acquired, probably autoimmune, antibody-mediated type I coagulation protein S deficiency (total, free and C4bp-bound). No previous instance of anti-PS antibody-associated PS deficiency had been reported. The patient was treated initially with prednisone, but the protein S levels did not rise until danazol was added, and dropped again after its withdrawal. PMID- 8213004 TI - Autoimmune haemolytic anaemia, Sjogren's syndrome and idiopathic thrombocytopenic purpura in a patient with sarcoidosis. AB - A unique occurrence of sarcoidosis autoimmune haemolytic anaemia (AIHA), Sjogren's syndrome and idiopathic thrombocytopenic purpura (ITP) in the same patient is reported. Although the occurrence of autoimmune disease with sarcoidosis is well known, a case in which several of these diseases coexist with sarcoidosis is rare. We present a man with longstanding sarcoidosis who developed AIHA. Sjogren's syndrome and ITP. This case report seems to be the first case in which three autoimmune diseases were accompanied by sarcoidosis in 1 patient. PMID- 8213005 TI - Nonisotopic semiquantitation of low molecular weight von Willebrand factor species: its use in pulmonary hypertension. PMID- 8213006 TI - Effect of prolactin on neutrophils and monocytes. PMID- 8213007 TI - Delegation of activities to auxiliary health care workers. PMID- 8213008 TI - Interdisciplinary group meets to identify and help resolve ethical and practical issues of long-term tube feeding. PMID- 8213010 TI - World Court Project: nuclear war--is the threat gone? PMID- 8213009 TI - An Alberta nurse--in Somalia. PMID- 8213012 TI - Nursing archives: what, why and how? PMID- 8213011 TI - Breastfeeding tidbits. PMID- 8213013 TI - Nursing's "finest hours": yours to create. PMID- 8213014 TI - Low-dose midazolam antagonizes cerebral metabolic stimulation by ketamine in the pig. AB - In order to test the hypothesis that low-dose midazolam reduces excitatory cerebral symptoms by attenuating ketamine-induced increases in the cerebral metabolic rate for oxygen (CMRO2), we compared the cerebral effects of a combination of an anesthetic dose of ketamine hydrochloride (10.0 mg.kg-1 i.v.) and a subanaesthetic dose of midazolam maleate (0.25 mg.kg-1 i.v., n = 6; or 0.10 mg.kg-1 i.v., n = 6) with results recently obtained with ketamine (10.0 mg.kg-1 i.v.) in normoventilated pigs anaesthetized with fentanyl, nitrous oxide and pancuronium. Cerebral blood flow (CBF) was measured with the intra-arterial 133Xe clearance technique, and CMRo2 was calculated from CBF and the cerebral arteriovenous oxygen content difference (CaVO2). The CMRO2 did not increase significantly. In contrast, the maximal increase in cerebral CaVo2 (by 56-59% at 10 min; P < 0.01) was similar to that induced by ketamine, since CBF was more depressed (by 35-45% at 1 min: P < 0.001) by ketamine-midazolam than by ketamine only. Midazolam was found to increase CVR (P < 0.01) and further depress CBF (P < 0.01), and to antagonize the ketamine-induced increase in CMRO2 (P < 0.05). Ketamine-induced effects on mean arterial pressure (MAP) and spectral electroencephalographic (EEG) voltage were not significantly altered by midazolam. The pharmacokinetics of ketamine, as measured during an 80-min period, were not affected by the concomitant administration of midazolam. We propose that a ketamine-midazolam combination comprising a low-dose fraction (1/100-1/40) of midazolam is superior to ketamine alone for anaesthetic use. PMID- 8213015 TI - Anaesthesia for coronary artery bypass grafting: opioid-analgesia combined with either flunitrazepam, propofol or isoflurane. AB - This is a prospective, open, randomized study comparing three different anaesthetic regimens with respect to haemodynamic stability (cardiac index and pressure measurements), ischaemia (ECG), and loss of awareness (midlatency auditory evoked potentials in 58 patients undergoing coronary artery surgery. Anaesthesia was based on fentanyl 0.01 mg kg-1 bw for induction and 0.8-2.0 mg h 1 in combination with nitrous oxide for maintenance before cardiopulmonary bypass and 0.2-0.6 mg h-1 without nitrous oxide during and after cardiopulmonary bypass. Eighteen patients were anaesthetised with flunitrazepam 0.01 mg kg-1 bw for induction and received thereafter 1-2 mg h-1 for maintenance (group F). In 40 patients anaesthesia was induced with etomidate and maintained with either isoflurane 0.4-1.2 vol% (group I) or propofol 4-10 mg kg-1 bw h-1 (group P). Vasodilators and inotropes were used for haemodynamic control when needed. Haemodynamic variables and ECG were studied at five timepoints (awake; after induction before surgery; after sternotomy; before cardiopulmonary bypass; and 20 min after separation from bypass). During surgical stimulation, vasodilators were needed significantly more frequently in group F, than in groups I and P. Surgery and sternotomy caused an increase in SVI and APs/SV in all groups. Differences between the groups were only found for systemic pressures, which after sternotomy were lowest in group I and before cardiopulmonary bypass were highest in group F. After termination of bypass all groups showed an increase in HR and a decrease in SVI, SVR, and LVSWI compared to the awake state, while CI remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213016 TI - Fentanyl and pethidine are antagonists on muscarinic receptors in guinea-pig ileum. AB - In order to evaluate the anticholinergic effect of fentanyl and pethidine, the influence of these drugs on the cumulative dose-response curves of carbacholine on the guinea-pig ileum has been investigated. Fentanyl and pethidine displaced the dose-response curve for carbacholine to the right in a parallel fashion, indicating competitive antagonism. Dissociation constants determined by an agonist EC versus antagonist plot were 0.22 mumol/l for fentanyl and 1.4 mumol/l for pethidine. It is concluded that during high-dose fentanyl anaesthesia, fentanyl may bind to muscarinic receptors and thereby produce a central anticholinergic syndrome. An additional finding was that the maximal response to carbacholine increased significantly when combined with pethidine. PMID- 8213017 TI - Intrathecal anaesthesia in patients under 45 years: incidence of postdural puncture symptoms after spinal anaesthesia with 27G needles. AB - Postoperative headache and backpain has limited the use of intrathecal anaesthesia in younger patients (15-45 years). We studied postoperative complaints among 133 healthy young patients (mean age 30.0 years, 47% females) who received spinal anaesthesia with a 27G needle. Postoperatively, 5 patients (4%) complained of postdural puncture headache (PDPH), 18 (14%) reported nonspecific headache, while 27 (20%) suffered from backpain. PDPH was not related to sex, age, day-care surgery, number of puncture attempts, or obstetric procedures. Backpain was significantly more common among females, and among in patients. One hundred and sixteen patients (87%) would accept spinal anaesthesia if they were to undergo the same surgical procedure again. Compared to other studies, we find the incidence of postanaesthetic complaints to be acceptable, also among day-care patients. The PDPH seemed to be lightly incapacitating, and only one patient required blood patching. PMID- 8213018 TI - Analysis of lung density by computed tomography before and during general anaesthesia. AB - Pulmonary structure was analysed by means of computed tomography (CT) in 20 lung healthy patients, relating tissue density to the attenuation value (AV) of a picture element. Regional density of pulmonary tissue (rlung) was determined using mean lung density in five regions of interest (ROI1-5) (sector method). Vertical and horizontal distributions of x-ray attenuation were analysed by density profiles, relating AV values to evenly distributed and normalised length scales. In group I (n = 12), CT-densitometry was obtained in awake, supine patients and after induction of general anaesthesia. In group II (n = 8), the effect of mechanical ventilation with positive end-expiratory pressure (PEEP, 1.0 kPa [10 cmH2O]) was studied. In the awake state, a vertical tissue density difference between the top and bottom of the lung was found in all patients, accounting for a mean of 0.235 g.cm-3 (right lung) and 0.199 g.cm-3 (left lung). Only minor changes were seen in the horizontal lung density profiles. After induction of anaesthesia, x-ray attenuation of ROI1-4 showed no significant differences when compared with the awake state. The basal lung areas (ROI5) revealed a significantly increased tissue density (P < or = 0.01), reaching mean values of 0.94 g.cm-3 (right lung) and 0.814 g.cm-3 (left lung). Similarly, vertical density profiles showed a markedly enhanced rlung of the bottom of the lung in all patients, interpreted as atelectasis. The amount of atelectasis accounted for 4.8 +/- 2.6% (right lung) and 4.7 +/- 2.1% (left lung) of the intrapulmonary area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213019 TI - Evaluation of postural stability by computerised posturography following outpatient paediatric anaesthesia. Comparison of propofol/alfentanil/N2O anaesthesia with thiopentone/halothane/N2O anaesthesia. AB - Simple clinical tests, like Romberg's test or a walking test, have proved to be inadequate guidelines for safe discharge after outpatient anaesthesia. A randomised study was therefore planned to compare postural stability measured by computerised posturography in 31 oral midazolam-atropine premedicated children aged 6.9 (s.e. 0.4) years who had been anaesthetised with either propofol/alfentanil/N2O or thiopentone/halothane/N2O. The sway velocity of the children was measured before premedication and 1, 2 and 3 h after the end of anaesthesia. Results show that sway velocity had returned to baseline values 3 h after the end of anaesthesia in all children who had received propofol/alfentanil/N2O and in 12 of the 15 children who had received thiopentone/halothane/N2O. The quantified version of the Romberg test performed with eyes open or closed was not impaired after anaesthesia, compared with the control values, indicating that in children poor equilibrium is not compensated by vision. The clinical recovery with respect to the times to eye opening, to responding to command or to being fully awake did not differ between the two anaesthesia methods. On the basis of recovery assessed by postural stability, propofol/alfentanil/N2O anaesthesia was not preferable to thiopentone/halothane/N2O anaesthesia after minor paediatric otolaryngological surgery. PMID- 8213020 TI - Cervical epidural steroid injection for cervicobrachialgia. AB - Fifty patients with chronic resistant cervicobrachialgia were randomly divided into two groups. Twenty-five patients (group A) were treated with cervical epidural steroid/lidocaine injections and 17 patients (group B) were treated with steroid/lidocaine injections into the posterior neck muscles. Another eight patients from group B were excluded from the study because they had started the process of litigation of insurance claims and their subjective analysis of pain relief might therefore not be trustworthy. One to three injections were administered at 2-week intervals according to the clinical response. All patients continued their various pre-study treatments: non-steroidal anti-inflammatory drugs, non-opioid analgesics and physiotherapy. Pain relief was evaluated by the visual analogue scale 1 week after the last injection and then 1 year later. One week after the last injection we rated pain relief as very good and good in 76% of the patients in group A, as compared to 35.5% of the patients in group B. One year after the treatment 68% of the group A patients still had very good and good pain relief, whereas only 11.8% of group B patients reported this degree of pain relief. These differences were statistically significant. We failed to achieve significant improvement of tendon reflexes or of sensory loss in both groups, but the increase in the range of motion, the fraction of patients who were able to decrease their daily dose of analgesics, and recovery of the capacity for work were significantly better in group A. We encountered no complications in either group of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213021 TI - Effects of flumazenil during administration of midazolam on pial vessel diameter and regional cerebral blood flow in cats. AB - We implanted closed cranial windows in ten cats in order to observe the response of pial vessel diameter by microscopy using fluorescein isothiocyanate-labeled dextran and regional cerebral blood flow (rCBF) by laser Doppler flowmetry during administration of midazolam and reversal with flumazenil. Midazolam was given at 0.8 mg.kg-1 x min-1 for 10 min and maintained at 0.04 mg.kg-1 x min-1 for 50 min (total 10 mg.kg-1). The diameter of arterioles and venules and rCBF showed no significant change. During the last 10 min of midazolam administration, flumazenil, given at 0.1 mg.kg-1 x min-1 for 10 min (total 1 mg.kg-1), caused an increase of MAP and rCBF (P < 0.01) at 5 min after infusion and diameter of larger arterioles (> 50 microns) and venules (50-100 microns) were dilated (P < 0.05). These results indicate that midazolam does not affect the diameter of cerebral arterioles and venules; however, the reversal effects of flumazenil against midazolam are transient vasodilation of larger arterioles accompanied by an elevation of MAP, and an increase in CBF. PMID- 8213022 TI - Acute hyperglycaemic effect of anaesthetic induction with thiopentone. AB - The acute effects of thiopentone on plasma glucose concentration and regulation in humans have not been well described. We therefore examined the effect of a single dose (6 mg/kg) of thiopentone on plasma glucose, insulin, glucagon, adrenaline and noradrenaline in 16 healthy women undergoing elective abdominal surgery. To assess involvement of the neuroendocrine system in the response to thiopentone, half of the patients received labetalol prior to induction of anaesthesia. Thiopentone injection resulted in a 50% increase in plasma glucose levels (P < 0.001) in both labetalol-treated and non-treated patients 90 s following its administration. This was associated neither with significant increases in plasma glucagon, adrenaline and noradrenaline nor with a decline in plasma insulin. We conclude that acute hyperglycaemia following thiopentone is most likely the consequence of a non-adrenergically-mediated increase in hepatic glucose release. PMID- 8213023 TI - Biochemical changes in malignant hyperthermia susceptible swine: cyclic AMP, inositol phosphates, alpha 1, beta 1- and beta 2-adrenoceptors in skeletal and cardiac muscle. AB - It has been presumed that alteration in the concentrations of second messengers leads to alterations in the function of the ryanodine receptor. Consequently, we have determined the basal content of cyclic AMP and inositol phosphates in skeletal and cardiac muscle of malignant hyperthermia (MH) susceptible (MHS) and healthy normal control (MHN) swine. Since alpha 1- and beta-adrenoceptors are linked to these second messenger systems, the densities of alpha 1- and beta adrenoceptors were also determined. In skeletal as well as cardiac muscle, a higher basal concentration of almost all of the inositol phosphates was found. Of all inositol phosphates measured, the presumed second messenger inositol 1,4,5 trisphosphate (1,4,5-IP3) was mostly concentrated in both tissues. Each MHS sample contained more 1,4,5-IP3 than the highest value observed in MHN muscle, indicating that a threshold of 1,4,5-IP3 concentration for determination of MHS or MHN status can be defined. In addition, MHS skeletal muscle contained more cAMP than MHN, whereas there was no difference between MHS and MHN in cardiac muscle. The changes observed in the different inositol phosphate and cAMP contents were not accompanied by an altered alpha 1- or beta-adrenoceptor density in skeletal or cardiac muscle between MHS and MHN. However, the total number of beta-adrenoceptors of MHN and MHS was significantly higher in cardiac (about 80 fmol/mg protein) than skeletal muscles (about 30 fmol/mg protein). The cardiac muscles revealed about 80% beta 1- and beta 2- and 20% beta 2-adrenoceptors, whereas skeletal muscles were characterized by over 95% beta 2 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213024 TI - A two-dose epidural morphine regimen in cesarean section patients: pharmacokinetic profile. AB - The maternal pharmacokinetics, metabolism of, and possible neonatal transmission of epidural morphine in cesarean section patients were investigated. Maternal plasma, breast milk, and maternal and neonatal urine concentrations of unconjugated and conjugated (UM and CM) morphine were measured in patients given two 5-mg doses of epidural morphine for post-cesarean section analgesia. The first dose was administered after delivery and the second dose 24 h later. Maternal venous blood samples (n = 10) were collected at times 0, 0.25, 0.5, 1, 2, 3, 4, 6, 12, and 24 h after each dose, and maternal urine was collected for three consecutive 24-h periods (n = 30). Maternal breast milk (n = 30), and neonatal urine samples (n = 20) were also collected. Serum, urine, and breast milk UM and CM levels were measured using radioimmunoassay. Pharmacokinetic values were calculated using noncompartmental analysis. The results were expressed as mean +/- 1 s.e. mean and analyzed using repeated measures analysis of variance and the paired t-test. Maternal serum UM remained 40-50% higher, and CM 50-100% higher in the first hour following dose 2 than the respective values after dose 1 (P < 0.05). Values for AUC, AUMC, T1/2, and MRT increased 28%, 83%, 35% and 36%, respectively, with the second dose (P < 0.05), while CI decreased 19% (P < 0.05) with no significant difference in Vss. Total urinary excretion of morphine decreased significantly from 1.98 +/- 0.15 mg on day 1 to 1.6 +/- 0.2 mg and 0.19 +/- 0.002 mg on days 2 and 3, respectively (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213025 TI - Effects of adenosine triphosphate (ATP) on somatosensory evoked potentials in humans anesthetized with isoflurane and nitrous oxide. AB - In order to examine the usefulness of adenosine triphosphate (ATP) as an adjuvant to anesthesia for surgery requiring intraoperative somatosensory evoked potential (SSEP) monitoring, we have studied the effects of ATP on SSEPs in patients anesthetized with isoflurane and nitrous oxide (N2O). A control recording of SSEP was performed while anesthesia was maintained with 0.5% end-tidal concentration of isoflurane in 60% N2O. The recordings were repeated after an ATP infusion had been added to this basal anesthesia at the rates of 100 micrograms.kg bw-1.min-1 and 200 micrograms.kg bw-1.min-1. SSEP was also studied when end-tidal isoflurane concentration was increased to 1.5% after cessation of ATP infusion. An infusion of ATP combined with 0.5% isoflurane and 60% N2O effectively inhibited an increase in blood pressure during surgery. The amplitude of the cortical component of SSEP was lowered by 1.5% isoflurane, which also increased both cortical and spinal latencies as well as central conduction time (CCT). In contrast ATP infusions at both rates induced no significant changes in latencies, amplitude and CCT. The results indicate that ATP infusion combined with 0.5% isoflurane in 60% N2O can be a useful anesthetic technique for intraoperative SSEP monitoring because adequate anesthetic depth can be maintained by a low concentration of anesthetics without further suppression of SSEPs. PMID- 8213026 TI - Metastatic pain in the parturient: treatment with patient-controlled epidural sufentanil. AB - A 30-year-old primigravid woman presented at 28 weeks gestation with severe pain related to metastatic gastric carcinoma. Pain control was achieved with epidural sufentanil, administered via a patient-controlled analgesia pump, for 5 days, prior to caesarean delivery. Considerations in deciding the optimal therapeutic regime are discussed. PMID- 8213027 TI - Increase in lactoferrin and elastase alpha-1-proteinase inhibitor complexes but lack of complement activation and IL-6 response following thoracic surgery. AB - Polymorphonuclear neutrophil (PMN) stimulation and degranulation can be mediated by the cytokines and by complement activation. The aim of the present study was to measure TNF alpha, IL-1 alpha, IL-6 and C3d in relation to postoperative increase in lactoferrin and elastase alpha-1-proteinase inhibitor (E alpha-1-PI) levels. Eleven patients undergoing thoracic surgery took part in the study. Blood leucocytes, E alpha-1-PI, lactoferrin and C3d were measured preoperatively, at the end of surgery and postoperatively, at 4 h and on day 1, 2, 3 and 5. TNF alpha, IL-1 alpha and IL-6 were measured preoperatively, at the end of surgery and postoperatively, at 4 h, and on days 1 and 5. The leucocyte count, lactoferrin and E alpha-1-PI levels increased significantly postoperatively (P < 0.01). There was no significant change in C3d values. Plasma IL-6 levels were unchanged in the postoperative period. Plasma TNF alpha and IL-1 alpha were detectable at low levels in only two and four patients, respectively. CONCLUSION: The postoperative increase in blood levels of PMN lactoferrin and E alpha-1-PI complexes observed in the present study was not accompanied by complement activation, or increased blood levels of IL-6. PMID- 8213028 TI - Hemodynamic changes associated with thermodilution cardiac output determination in canine acute blood loss or endotoxemia. AB - Since the technique of thermodilution (TD) cardiac output measurement, per se, causes hemodynamic alterations, the author examined whether the alterations elicited by iced injectate are augmented in the presence of acute blood loss or endotoxemia, compromised conditions frequently associated with critically ill patients. Acute blood loss (N = 8) and endotoxemia (N = 8) were induced by withdrawing arterial blood approximately 20-30 ml.kg-1 over 30 min and by a slow intravenous infusion of E. coli endotoxin 2.5-3.0 mg.kg-1 over 10 min, respectively, in anesthetized dogs. The magnitudes of decreases in mean arterial and pulmonary artery pressures during slowing of heart rate (HR) following injection of iced injectate 3 ml were slightly less in acute blood loss than in normovolemia, whereas in endotoxemia the degree of mean arterial pressure decrease during slowing of HR following iced injectate 3 ml was slightly less as compared with that before endotoxemia. However, the alterations in other hemodynamic variables following injection of iced injectate 3 ml were similar between dogs with and without acute blood loss or endotoxemia. No profound hemodynamic changes were observed during any TD cardiac output measurements under both conditions. Cardiac output estimated by TD correlated closely with pulmonary blood flow measured by electromagnetic flowmeter in endotoxemia (r > 0.9) but not during acute blood loss. These results indicate that TD cardiac output determination does not cause serious hemodynamic alterations in endotoxemia or acute blood loss, and can estimate right ventricular output accurately in endotoxemia but not in acute blood loss. PMID- 8213029 TI - A double-blind comparison of lidocaine and mepivacaine during epidural anaesthesia. AB - The effects of epidural anaesthesia with plain 2% lidocaine or mepivacaine were compared in 200 patients undergoing extracorporeal shock wave lithotripsy in a double-blind manner. The onset, spread, duration and quality of analgesia were similar in both groups. The numbers of patients who needed vasoconstrictor or atropine were almost equal in both the lidocaine and the mepivacaine groups. Mild but significant hypotension continued for a longer period in the mepivacaine group than in the lidocaine group. A transient decrease in arterial oxygen saturation was seen in two patients receiving lidocaine and in three patients receiving mepivacaine. Mild systemic toxicity was observed in eight patients in both groups, although serious complications such as convulsions did not occur. It is concluded that both drugs can be used equally safely for epidural anaesthesia, although the maximum recommended doses differ. PMID- 8213030 TI - Changes in the T-wave amplitude of ECG during isoflurane anaesthesia. AB - R/T-wave amplitude ratio of electrocardiogram (ECG), heart rate (HR) and systolic arterial pressure (SAP) were recorded in 15 patients awake, at 1 minimal alveolar concentration of isoflurane before and during surgery, and in deep anaesthesia (electroencephalogram burst suppression) during surgery. R/T-wave amplitude ratio and HR were sensitive to both surgery and changes in the level of isoflurane anaesthesia; induction of anaesthesia, skin incision and the rapid increase in the concentration of isoflurane all significantly decreased the T-wave amplitude, without influence on the R-wave. Changes in the T-wave amplitude correlated directly to HR. SAP increased at skin incision and decreased when the anaesthesia was deepened. The authors conclude that the R/T-wave amplitude ratio of ECG provides a reliable method for monitoring the sympathetic tone during isoflurane anaesthesia. PMID- 8213031 TI - Effect of intravenous diclofenac or indomethacin on the emergence from anaesthesia for tonsillectomy. AB - We evaluated the effects of a single dose of diclofenac (75 mg) or indomethacin (50 mg) on intraoperative events and on the early recovery phase. The study was performed in a randomised, double-blind, placebo-controlled fashion in 63 adult patients scheduled for elective tonsillectomy. Study infusions started intravenously immediately after the induction of general anaesthesia with thiopentone; maintenance was with N2O/O2 and halothane. After intubation with the aid of suxamethonium, the patients breathed spontaneously via a Bain coaxial system. Perioperative events (bleeding tendency, bleeding, need for pain medication, physical recovery) were recorded with the aid of a questionnaire applied to the anaesthesia nurses and estimation of vigilance, attention, concentration, short-term memory, and simple motor speed during recovery was with the aid of three neuropsychological tests (thumb tapping test, digit span test and homogenic interference test). No significant differences between the three groups were found in systolic and diastolic arterial pressures, the results of the questionnaire, and those of the neuropsychological tests. The ability to keep the head elevated for at least 5 s recovered significantly later (P < 0.05) and heart rate levels in the indomethacin group were significantly lower (P < 0.001) than in the other two groups. No enhanced bleeding during the perioperative period was observed. Diclofenac and indomethacin in the doses used in our study have only a marginal effect on the patient's emergence from anaesthesia. PMID- 8213032 TI - Precision of a new bedside method for estimation of the circulating blood volume. AB - The present study is a theoretical and experimental evaluation of a modification of the carbon monoxide method for estimation of the circulating blood volume (CBV) with respect to the precision of the method. The CBV was determined from measurements of the CO-saturation of hemoglobin before and after ventilation with a gas mixture containing 20-50 ml of CO for a period of 10-15 min. A special Water's to and fro system was designed in order to avoid any leakage when measuring during intermittent positive pressure ventilation (IPPV). Blood samples were taken before and immediately after ventilation with the CO gas mixture. The amount of CO administered during each determination of CBV resulted in an increase in the CO saturation of hemoglobin of 2.1%-3.9%. A theoretical noise propagation analysis was performed by means of the Monte Carlo method. The analysis showed that a CO dose corresponding to an increase of less than 2% will result in an unacceptable coefficient of variation of repeated estimates. In the experimental study the coefficient of variation of repeated estimates of CBV was determined from duplicate measurements of CBV in nine healthy subjects and in nine intensive care patients. The coefficients of variation were 6.2% and 4.7% in healthy and diseased subjects, respectively. Furthermore, the day-to-day variation of the method with respect to the total amount of circulating hemoglobin (nHb) and CBV was determined from duplicate estimates separated by 24 48 h. In conclusion, determination of CBV can be performed with an amount of CO that gives rise to a harmless increase in the carboxyhemoglobin concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213033 TI - Undiagnosed amyotrophic lateral sclerosis and respiratory failure. AB - Two patients suffering from exacerbation of chronic respiratory insufficiency due to previously undiagnosed amyotrophic lateral sclerosis are reported. Both patients had a false diagnosis of asthma with a restrictive component. The diagnosis had been made after pulmonary function studies, and both patients had also received treatment for asthma. A central etiology was suspected when weaning from mechanical ventilation proved unsuccessful during respiratory failure, necessitating intensive care. A neurologic examination and a typical electroneuromyography recording confirmed the diagnosis of amyotrophic lateral sclerosis. Neuromuscular disorders must be excluded when treating patients with respiratory failure, even if they already have the diagnosis of chronic pulmonary disease. PMID- 8213034 TI - The additional effect of piroxicam on pain and lung function after thoracotomy. PMID- 8213035 TI - Immunoelectron microscopic distribution of actin in the spermatids and epididymal spermatozoa of the mouse. AB - The distribution of actin in spermatids and epididymal spermatozoa of the mouse was examined by electron microscopy with immunogold procedures using two monoclonal antiactin antibodies. Actin was identified by immunoblotting of proteins extracted from either whole spermatozoa or tail fractions. In round spermatids, actin immunolabeling was detected in the subacrosomal space. Labeling increased during the elongation phase, and then decreased and completely disappeared before spermiation. No labeling was found in epididymal spermatozoa and residual bodies. Our results suggest actin redistribution or the absence of G actin from the head to the flagellum in mature murine spermatids, as previously shown in other studies in various mammals. PMID- 8213036 TI - Embryological study of nasal cavity development in human embryos with reference to congenital nostril atresia. AB - An infant with congenital absence of the nostrils, incomplete prolabium, incomplete premaxilla, nasal cavity without septum, and cleft palate is presented. To clarify the embryological development of the nostril, serial sections of many embryos and fetuses of various stages were examined. Recanalization of the nostril, resulting from resorption of the temporary nasal epithelial plug, was observed in a 13- to 15-week fetus. Although textbooks of human embryology describe its occurrence in the 6th month or 24th week of fetal life. This finding suggests that the embryological cause of congenital nostril atresia, in the present case, may have been persistence of the plug. PMID- 8213037 TI - Occurrence of melanosome-containing Merkel cells in mammalian oral mucosa. AB - The occurrence and fine structure of Merkel cells with melanosomes in the labial epithelium of the dog and cat were studied by electron microscopy. These melanosomes were polarized in the Merkel cell cytoplasm opposite to the major aggregation of dense-cored granules and the closely abutting nerve terminal. None of melanosomes was found in the Golgi complex region where a few immature dense cored granules were observed. This may suggest that the melanosomes are not produced in the Merkel cell, but are taken from the melanocytes like in keratinocytes. The possible phagocytotic ability of Merkel cells is discussed. PMID- 8213038 TI - Seam structures observed along the junctional line of Hertwig's epithelial 'root' sheaths in rat incisors. AB - Linear structures were occasionally found on the lingual surface of the cementum of infant rat incisors along the long axis of the incisors, which are teeth that grow continuously from a persistent odontogenic organ. The observations strongly suggest that these linear structures on the junctional line of Hertwig's epithelial 'root' sheaths correspond to the seams on the multirooted molar teeth of rats. PMID- 8213039 TI - Morphometric analysis of parathyroids in hypophysectomized rats in normocalcaemic and short-term induced hypocalcaemic conditions. AB - The ultrastructure of parathyroid glands of hypophysectomized rats in normo- and hypocalcaemic conditions was qualitatively and quantitatively analysed. Parathyroid glands of both intact and hypophysectomized rats comprised cells of similar shape and staining intensity and of an equal number of cells in mitosis. Cell volume was not affected but the surface area of plasma membrane, RER and Golgi complex was increased in parathyroid cells after hypophysectomy. Parathyroid cells of both intact and hypophysectomized rats responded to hypocalcaemia by a drastic increase in surface area of the plasma membrane and a decrease in surface area of the Golgi complex. Since RER, Golgi complex and plasma membrane are concerned with secretion of parathyroid hormone, the data suggest that (1) the pituitary has either no effect on parathyroid cells, or a possibly stimulating effect can be compensated after hypophysectomy, or the pituitary even has a suppressive effect on parathyroid cells, and (2) the responsiveness of parathyroid cells to changes in serum calcium is unimpaired after hypophysectomy. PMID- 8213040 TI - Morphological alterations in the elastic fibers of the rabbit craniomandibular joint following experimentally induced anterior disk displacement. AB - Elastic fibers are important components of the connective tissue that attaches the articular disk of the craniomandibular joint (CMJ) to the skull and mandible. Biopsies of the articular disk proper and bilaminar zone (BZ) tissues from patients with anterior disk displacement (ADD) have shown previously that there is a marked loss of elastic fibers. In the present study, the effects of inducing ADD on the elastic fibers in the rabbit CMJ disk proper, BZ and condylar cartilage were investigated. The right CMJ was exposed surgically and the discal attachments were severed except for the BZ attachments. Then, the disk was displaced anteriorly and sutured to the zygomatic arch. The CMJs were removed after 1, 2 or 6 weeks and processed for histochemical demonstration of elastic fibers. The results showed osteoarthritic changes following ADD, and a significant decrease in the number of the elastic fibers in the disk proper and BZ. The remaining elastic fibers were abnormal in their appearance and orientation. In addition, ADD led to the appearance of fine elastic fibers among the chondrocytes in the hyaline cartilage of the condyle that were not present in the cartilage of the control condyle. We conclude that induced ADD can lead to a significant loss of elastic fibers in the articular disk, and result in the appearance of elastic fibers within the cartilage of the mandibular condyle. PMID- 8213041 TI - In vivo effect of gangliosides on non-obese diabetic mice. AB - Non-obese diabetic mice were administered 150 mg/kg body weight of Cronassial daily from the 5th to the 11th week of life. Animals were killed either at the end of the treatment with Cronassial (week 11) or at week 21. The results obtained demonstrated that the appearance of the insulitis in control and treated animals at 11 and 21 weeks did not show a significant difference. The only effect of ganglioside treatment was to slow the rate of rise in glycaemia and the progression of the islet cyto-architectural derangement. In our opinion, this is not sufficient to prove the effectiveness of this drug in reducing the final diabetes incidence. PMID- 8213042 TI - Vitamin D (soltriol) target cells in the harderian gland of the Siberian hamster (Phodopus sungorus). AB - Harderian glands of female and male Siberian hamsters (Phodopus sungorus) were studied after a subcutaneous injection of 3H-dihydroxycholecalciferol (vitamin D, soltriol). Autoradiograms revealed the presence of nuclear concentration of the hormone in certain alveolar cells and in myoepithelial cells. The proportion of labeled cells varied between 5.5 and 19% of the total cell number, with an average of 9.5% in female and 12.4% in male hamsters. The data suggest that the functions of the Harderian gland could undergo seasonal changes under the control of vitamin D. PMID- 8213043 TI - Study of sympathetic innervation of cranial bones by axonal transport of horseradish peroxidase in the rat: preliminary findings. AB - This study performed by intraneuronal tracing directly demonstrates the presence of sympathetic postganglionic fibers in the cranial vault of the rat. Superior cervical sympathetic ganglia were injected with horseradish peroxidase (HRP), and after a 48-hour period, to permit anterograde axonal transport, the animals were sacrificed after in situ perfusion. An area of the calvaria that included portions of the frontal and parietal bones was fixed, decalcified and sectioned. HRP-containing axons were localized in the developing frontal and parietal bones of the calvaria. Adrenergic innervation was not demonstrated in sutural tissue (superior sagittal, coronal or metopic) by this technique. To our knowledge, this study is the first to trace sympathetic nerve fibers in the rat calvaria by intra axonal transport of HRP. PMID- 8213044 TI - Catecholaminergic innervation of oxytocin neurons in the paraventricular nucleus of the rat hypothalamus as revealed by double-labeling immunoelectron microscopy. AB - The catecholaminergic innervation of neurons that contain oxytocin in the paraventricular nucleus (PVN) of the rat hypothalamus was examined by a combination of methods in the same tissue sections at the electron-microscopic level as follows: (1) Rats were treated with 5-hydroxydopamine (5-OHDA) with peroxidase-antiperoxidase (PAP) staining of sections for oxytocin prior to embedding. (2) Preembedding immunoperoxidase staining with avidin-biotin complexes was used to demonstrate tyrosine hydroxylase (TH) activity, with postembedding staining with immunocolloidal gold for visualization of oxytocin. (3) Prior to embedding, a double-staining technique was used that was based on consecutive staining with silver-gold-intensified PAP complex and 3,3' diaminobenzidine. We used an antiserum against oxytocin and an antiserum against dopamine-beta-hydroxylase (DBH) for localization of antigens. We found that TH- and DBH-like immunoreactive terminals were distributed throughout the rat hypothalamus and were abundant in all parts of the PVN. Ultrastructural observations revealed 5-OHDA-labeled, TH- or DBH-like immunoreactive axon terminals that contained granular vesicles (70-80 nm in diameter) and small clear synaptic vesicles (30-50 nm in diameter). The terminals appeared at times to be making synapses with cell bodies and with the processes of oxytocin-containing neurosecretory neurons in the PVN. These findings provide morphological evidence for a direct synaptic influence of catecholaminergic elements on the secretory activity of oxytocin-containing neurosecretory neurons in the rat hypothalamic PVN. PMID- 8213045 TI - Fibulo-tibial weight index--a new criterion for sex identification based on the lower leg bones. AB - This study was designed in an attempt to determine whether the fibula can provide reliable information for sexing human bones, if measurements include tibial indices. Our results allow us to introduce a new criterion for sexing long bones: the fibulo-tibial weight index. Bone weight was determined, together with conventional measurements, such as maximum bone length and mid-shaft circumference. The materials consisted of dried tibiae and fibulae of 71 recently decreased Japanese males and 31 females. The mean value of the fibulo-tibial weight index was very significantly greater in females than in males. In discriminant analysis, the rate of correct sex discrimination was improved by the inclusion of the fibulo-tibial weight index. PMID- 8213046 TI - [Asymptomatic nerve hypertrophy in lepromatous leprosy]. PMID- 8213047 TI - [Location of single skin lesions of paucibacillary leprosy]. AB - In this paper the authors study the sites of single lesions in 317 paucibacillary patients registered at the outpatient units of the CMS Jorge Saldanha and the Curupaiti State Hospital in Rio de Janeiro, Brazil. The preferential sites of lesions in the population studied, their relation with age and sex and factors likely to influence their distribution are discussed. The findings are compared with other similar studies performed in Asia and Africa. PMID- 8213048 TI - Attempts to cultivate Mycobacterium leprae in fat tissue. AB - The behaviour of M. leprae in fat tissue was studied. Preadipocyte cells were infected with M. leprae and injected intradermally (I.D.) into nude mice. Adipose nodules obtained by in vivo differentiation of infected cells were maintained in vivo for 3 months and subsequently incubated in vitro for 3 months. Counts of bacilli showed no increase over this 6 months period. It is concluded that undifferentiated preadipocyte and mature fat cells are not permissive for M. leprae. The morphological changes observed following passage of M. leprae into adipose nodules might be related to the process of adipose cell differentiation. PMID- 8213049 TI - Myiasis in leprosy. AB - During the 1989-1991 year period, leprosy patients with various ulcers, attending the surgical O.P.D. at CJIL, Agra were seen. Of these, 64 cases were found to be infested with maggots. Live maggots were collected in all cases from different sites viz. nasal cavity, hand, great toe and second toe. It was possible to rear the maggots into flies in 53 out of 64 cases. In 11 cases the maggots did not survive and died in the early part of their life cycle. Four different types of flies were identified viz. Sarcophaga haemorrhoidalis, Chrysomya bezziana, Callitroga americana and Musca domestica. PMID- 8213050 TI - Characterization of microbial flora of leprous ulcers infested with maggots. AB - Swabs from 64 maggot infested leprosy ulcers before and after treatment for maggots and 100 non-infested leprosy ulcers were studied for the bacterial flora. From maggot infested ulcers (before treatment), the cultures usually showed mixed growth. Among the Gram positive isolates, Staphylococcus aureus (37%), S. albus (18%) and Streptococcus pyogenes (36%) were frequently isolated. Gram negative bacteria isolated were Proteus spp. (21%) and Escherichia coli (7%). Anaerobic bacteria isolated were Micrococcus (3%) and Bacteroides (4%). After treatment of maggot infested ulcers, S. aureus (36%) continued to be isolated with almost the same frequency. The isolates of other Gram negative organisms were slightly reduced. Among the Gram negatives the Proteus spp. (10%) were also less in number. In few cases Neisseria (3%) was found. Anaerobic isolates were M. luteus (2%) and B. necrophorus (3%). From the cases without maggot infestation, a single organism was isolated from 16 cases and 84 mixed cultures were obtained. Isolates included the aerobic Gram positives S. aureus (46%), S. albus (21%) and S. pyogenes (38%), and the Gram negative Proteus spp. (19%) and E. coli (7%). The anaerobic isolate was M. luteus (3%). From this study no apparent association between the type of bacterial flora and maggot infestation could be observed. PMID- 8213051 TI - Radiosurgery of cerebral arteriovenous malformations with a linear accelerator: preliminary report. AB - The authors present the results obtained in seven patients with arteriovenous malformations treated with radiosurgery on a linear accelerator. In four patients obliteration of the malformation was obtained after one year. Two of the patients had a transient period of acute brain oedema surrounding the radionecrotic nidus with neurological signs. The present position of radiosurgery in the treatment of arteriovenous malformations is discussed. PMID- 8213052 TI - [Symptomatology of language disorders in cerebral palsy with mutism]. AB - Language disturbances in cerebral palsy with mutism. The analysis of the afferent side of language in 18 cerebral palsy children with no oral expression shows that they form a very heterogeneous population. The semiological analysis concerning comprehension leads to their classification into four main groups akin to the classical dysphasia syndromes. Major agrammatism occurring in phonologico syntactic dysphasia. Sensory dysphasias (or verbal deafness). Mixed (or global) dysphasias. Motor dysphasias: phonological programmation disturbances (anarthria) and motor production disturbances (dysarthria). The disclosure of these various dysphasias allows for specific rehabilitation and for education procedures suitable for each individual patient. PMID- 8213053 TI - Structural and vascular permeability abnormalities associated with lacunes of the human brain. AB - Histopathological and immune-histochemical studies were carried out in four cases with multiple lacunes of the central grey matter and in control cases without such lesions. Routine light microscopic techniques were applied on paraffin embedded material to identify lesions that may represent developing lacunes. In addition, polyclonal antisera to human albumin, IgG, fibrinogen and fibronectin were chosen as markers for extravasated plasma proteins. The brain tissue between lacunes contained several forms of focal injuries which may represent precursors of lacunes. Such lesions included foci of status spongiosus and status cribrosus, regions with dilated extracellular spaces and astrocytic gliosis, and multi locular cysts. These "lacune-associated lesions" often included albumin immune reactivity in extracellular spaces, nerve cell bodies and astrocytes. Less frequently signs of extravasated IgG, fibrinogen and fibronectin were identified. Thus, lacunes of the human brain frequently showed signs of antigenic sites to albumin. The extracellular deposits probably represent extravasated material from the blood. Vasogenic and cytotoxic oedema combined with other factors probably play important roles during the formation of some of the lacunes. PMID- 8213054 TI - Regional brain atrophy in HIV-1 infection: association with specific neuropsychological test performance. AB - Quantified magnetic resonance imaging (MRI) was related to neuropsychological (NP) test scores in an asymptomatic HIV-1 seropositive group, a non-demented AIDS/ARC group, a group of subjects with HIV-1 dementia, and a seronegative control group. The MRIs were quantified using three planimetric measures of brain structure: the bicaudate ratio (a measure of caudate region atrophy), the bifrontal ratio (a measure of frontal region atrophy), and the ventricle to brain ratio (a measure of overall cerebral atrophy). Cognitive performance was assessed with standard NP tests. Significant correlations between the MRI ratios and many of the NP tests were observed. Of the tests grooved pegboard, part B of the trail making test, the verbal fluency test, and the digit span forward were associated with MRI abnormalities. The bicaudate ratio was most closely associated with the NP tests. These findings indicate that ventricular enlargement, especially in the region of the caudate, is closely related to poor NP test performance in HIV-1 infection. PMID- 8213055 TI - Neuropsychological performance in HIV-1-infected drug abusers. AB - Twenty-five HIV-seropositive drug abusers (DA+HIV+) (groups II-III and IV [A, C2 and E] of the CDC classification) were evaluated by use of the WAIS scale to determine any possible involvement of cognitive functions in the not yet overt phases of AIDS. The results were compared with those obtained in two control populations composed of 19 seronegative drug abusers (DA+HIV-) and 24 healthy subjects (DA-HIV-) to evaluate, in addition to the disease, the possible effect of the use of alcohol and toxic substances on cognitive performance. In spite of the small number of subjects, the study indicated that drug abuse is the main factor, among those analyzed, in determining a decline in cognitive functions. PMID- 8213056 TI - Brainstem involvement in high functioning autistic children. AB - To determine involvements of the brainstem and/or cerebellum in autism, we compared midsagittal magnetic resonance images of the brains of high functioning autistic children with those of normal controls. We found that the midbrain and medulla oblongata were significantly smaller in these autistic children than in the control children. The pons area did not differ between the two groups, nor was there any difference in the cerebellar vermis area. The ratio of the brain stem and cerebellum to the posterior fossa area did not differ significantly between the high functioning autistic and the control children. A positive correlation between age and area of the cerebellar vermis was observed in autistic children but not in control children. Thus, it was suggested that significant anatomical changes in the midbrain and medulla oblongata existed in the autistic children and that growth of the cerebellar vermis in autistic children was different from normal children. PMID- 8213057 TI - Movement-related cortical potentials in patients with cerebellar degeneration. AB - We studied the topographic distribution of scalp-recorded, averaged movement related cortical potentials occurring immediately before and after the onset of voluntary movements in six patients with cerebellar degenerative disease. We placed 26 electrodes on the scalp overlying the sensorimotor area and recorded cortical potentials related to abduction of the index finger. The amplitudes and latencies of the potentials were normal in all patients except two, in whom the negative slope (NS') was absent. All patients had an abnormal topographic pattern of potentials compared with normal subjects. The initial slope of motor potential (isMP), which was focal and contralateral in the normal subjects, was diffuse and bilateral in the patients. The topography of the frontal peak of motor potential (fpMP) was more posterior in the patients than in normal subjects. The patterns found in this preliminary study indicate a derangement of sensorimotor cortex activity in voluntary movement as a consequence of cerebellar dysfunction. PMID- 8213058 TI - Practical aspects of 3,4-diaminopyridine treatment of the Lambert-Eaton myasthenic syndrome. AB - 3,4-Diaminopyridine (3,4-DAP) given alone or combined with pyridostigmine is the recommended basic therapy in the Lambert-Eaton myasthenic syndrome (LEMS). We present and exemplify our routine test protocol for monitoring drug introduction and treatment regimen of cholinergic drugs in LEMS. The individual drug responses vary and no recommended standard doses exist. Routine electrophysiological repetitive nerve stimulation studies recording amplitude of initial compound muscle action potential (CMAP) in thenar muscles correlate excellently with clinical myasthenic muscle power tests in clinically affected muscle groups. Therefore repetitive clinical muscle power tests, that often are complicated by painful myalgia and activation potentiation, can be replaced by recordings of CMAP in the introduction and clinical follow up of cholinergic drug treatment in LEMS. Also, adverse effects and other treatment problems from the experience of continuous treatment of 19 LEMS patients with 3,4-DAP for up to 10 years are presented. PMID- 8213059 TI - Axonal motor and sensory neuropathy in myotonic dystrophy. AB - We report the neurophysiological findings from 24 subjects with myotonic dystrophy of Steinert and the histological findings in two of them. The conduction data is compared with that of a group of subjects with Landouzy Dejerine muscular dystrophy. In 46% of cases, the electrophysiological data revealed slight and generalized axonal neuropathy. Histological results of sural nerve confirmed axonal damage of sensory fibres. The neuropathy was not correlated with age of patients, duration or onset of the disease, nor with the state of the deep reflexes; it did not show signs of progressing and is probably one of the multisystemic manifestations of gene pleiotropism. PMID- 8213060 TI - Carpal tunnel syndrome and hyperthyroidism. A prospective study. AB - We carried out a prospective study to determine the frequency and evolution of carpal tunnel syndrome (CTS) in patients with hyperthyroidism. An initial survey revealed CTS in 5% of these patients when hyperthyroidism was diagnosed. During the clinical and neurophysiologic follow-up for a two-year period, four more patients developed CTS; of these, two had uncontrolled hyperthyroidism, and the other two had iatrogenic hypothyroidism. The clinical and neurophysiologic evolution suggests a relationship between both diseases. The symptoms of CTS remitted if endocrinopathy is controlled. Surgery is, in general, not necessary. CTS can be considered another peripheral neurological manifestation associated with hyperthyroidism. PMID- 8213061 TI - Complete bilateral oculomotor palsy: the only clinical sign of subarachnoid hemorrhage in leukemia. AB - We report the original case of a patient with acute myelogenous leukemia who presented with a painless, complete bilateral oculomotor palsy during induction chemotherapy. Headache, signs of meningeal irritation or further neurological symptoms were absent throughout the course of illness. The CT revealed a subarachnoid hemorrhage (SAH). Within a day of the onset of symptoms, the oculomotor palsy subsided completely with no residual damage. To our knowledge, this is the first described case of SAH in leukemia with complete bilateral oculomotor palsy being the only clinical symptom. Furthermore, the spontaneous remission of this pathological condition is an extremely rare event. PMID- 8213062 TI - Excitatory amino acids and amyotrophic lateral sclerosis. PMID- 8213063 TI - T-cell subsets in the cerebrospinal fluid and peripheral blood of multiple sclerosis patients treated with high-dose intravenous methylprednisolone. AB - To determine the effects of high-dose intravenous methylprednisolone (MP) on lymphocytes and lymphocyte subpopulations in the cerebrospinal fluid (CSF) and peripheral blood (PB) in multiple sclerosis (MS) patients, we studied 67 patients with definite MS treated with MP. They were classified according to the disease course: 32 chronic progressive (CP) patients, 25 relapsing-remitting (RR) patients, and 10 patients with a chronic progressive disease course accompanied by relapses and remissions (CP + RR). MS patients were treated with 1000 mgr intravenous MP daily for 10 consecutive days. Before and after MP treatment we simultaneously studied CSF and PB CD3+, CD4+, CD8+, CD20+, and Ia1+ cell subsets. Kurtzke's Expanded Disability Status Scale (EDSS) was used for clinical evaluation. Progression rate was defined as the ratio of EDSS to disease duration. Thirteen patients with lumbar disk herniation were investigated as controls. Before MP, we found in MS patients, especially in the CP group, significantly lower CD4+ T-cell percentages in the PB with respect to controls (p < 0.05). The percentage of CD4+ T-cells in the CSF of MS patients was significantly higher compared with PB (p = 0.0001), and tended to be higher than in controls (p = 0.072). The CSF mononuclear cell counts were significantly correlated with higher percentages of CSF CD3+ (r = 0.40) and CD4+ (r = 0.47) T cells and lower CSF CD8+ (r = -0.33) T-cell percentages. B-cell percentages in the CSF were significantly elevated compared with controls for all MS groups. No relation could be obtained between T- or B-cell subsets and EDSS or progression rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213064 TI - Comparison of patient and staff assessment of MS patients' health status. AB - This study compared change scores obtained on patient self-reported symptoms (MS RS) with the neurological examination of the Kurtzke Functional Systems (FS) and change scores obtained on patient self-reported activities of daily living (ADL MS) with the neurologist-determined Expanded Disability Status Scale (EDSS) that were obtained from two separate times separated by approximately seven months for 100 patients with multiple sclerosis. Percent agreement based on < or = 1 unit difference between patient and neurologists' change scores (Time 2-Time 1) ranged between 73% and 86% for MS-RS and FS measures and was 72% for ADL-MS and EDSS. Together, the ADL and MS-RS patient self-report scales provide health status information from the patient's perspective that can be useful in guiding the physical examination, in making comparisons from visit to visit and/or between visits, in assessing patients' quality of life, and in increasing patient satisfaction with medical care. PMID- 8213065 TI - GFAP-specific oligoclonal bands in the CSF of a patient with acute myelitis. AB - The specificity for GFAP (glial fibrillary acidic protein) of oligoclonal IgG bands in the CSF of a patient with acute myelitis was demonstrated by isoelectric focusing and affinity blotting. Findings were confirmed by western blotting using a monoclonal antibody to GFAP as a reference. Immune reactions to this astrocyte protein are considered as arising secondary to spinal cord tissue lesion. PMID- 8213066 TI - Pentoxifylline inhibits experimental allergic encephalomyelitis. AB - Pentoxifylline, a widely used methylxanthine, has been proven to inhibit the production and action of the cytokine TNF alpha. Since it has been suggested that TNF alpha is the major cytokine involved in the pathogenesis of multiple sclerosis, we tested pentoxifylline for its capacity to prevent experimental allergic encephalomyelitis (EAE). 26 Lewis rats with acute EAE were treated with either pentoxifylline or saline. The pentoxifylline treated rats showed a significantly lower incidence of clinical signs as well as significantly lower histological inflammation. The exact mechanism of this preventive effect remains to be clarified but it might be mainly related to inhibition of TNF alpha release from central nervous system macrophages. PMID- 8213067 TI - Invasion of experimental rat brain tumor: early morphological changes following microinjection of C6 glioma cells. AB - We present morphological data of the early stage of tumor invasion in the central nervous system. C6 rat glioma cells were injected into the caudate-putamen of rat brain using glass micropipettes to minimize traumatic reactions. Four days after the inoculation, we examined the tumor-brain interface using light and electron microscopy. Ultrastructurally the tumor processes were attached to the perivascular basement membrane instead of the astroglial end-feet. At the tumor periphery, the vessel walls were in contact with both tumor processes and astroglial end-feet. Astrocytes withdrew their processes from the vascular walls and changed into a reactive phenotype, while the neuronal cells remained virtually intact, even when surrounded by tumor cells. Immunohistochemical study using C6 cells labeled with bromodeoxyuridine showed migration of the cells toward the perivascular space that was distant from the site of injection. These observations represent the earliest morphologically detectable changes of the tumor-brain interface, and suggest that the C6 cells possess the characteristics of high affinity to the endothelial basement membrane and invade along the preexisting blood vessels with brain parenchymal infiltration. PMID- 8213068 TI - Defects of neuronal migration and the pathogenesis of cortical malformations are associated with Small eye (Sey) in the mouse, a point mutation at the Pax-6 locus. AB - The mouse Small eye (Sey) locus is situated on chromosome 2. Molecular analyses have shown that SeyNeu represents a point mutation leading to a splice site error and loss of the functional gene product. The Sey locus has been shown to be identical with the paired box (Pax)-6 gene, which contains paired-like and homoeobox domains and is a developmental control gene. Pax-6 expression occurs in many parts of the central nervous system during embryogenesis. Therefore, we may expect the Sey mutation to result in abnormal development of the central nervous system. The present study shows that Pax-6 mutation has a bimodal effect upon neurogenesis in mouse: it causes a delay of premigratory neurons in a stage-, region-, and gene-dose-dependent manner. Additionally, Sey mutation impairs axonal growth and differentiation. Neurons of the cortical plate cease differentiation on approximately day 16 of gestation and appear to have increased cohesion: their cytoplasm is swollen and vacuolated. These changes coincide both with reduced formation of axons and with the onset of vacuolar degeneration in existing axons, glial cells and radial glial fibers. Consequently, there is an impairment of the peripheral migration of putative neurons so that the neonatal lesion pattern of the neocortical roof becomes dominated by a broad spectrum of neuronal migration disorders. PMID- 8213069 TI - Initiation of protein synthesis and heat-shock protein-72 expression in the rat brain following severe insulin-induced hypoglycemia. AB - Following stress such as heat shock or transient cerebral ischemia, global brain protein synthesis initiation is depressed through modulation of eucaryotic initiation factor (eIF) activities, and modification of ribosomal subunits. Concomitantly, expression of a certain class of mRNA, heat-shock protein (HSP) mRNA, is induced. Here we report that the activity of eucaryotic initiation factor-2 (eIF-2), a protein that participates in the regulation of a rate limiting initiation step of protein synthesis, transiently decreases following insulin-induced severe hypoglycemia in the rat brain neocortex. Expression of HSP 72, a 72-kDa HSP, in surviving neurons was seen at 1-7 days of recovery following 30 min of hypoglycemic coma, but not at 1 h and 6 h of recovery. In the neocortex, HSP 72 was first seen in layer IV, and later also in surviving neurons in layer II. In the CA1 region and in the crest of dentate gyrus, HSP 72 expression was evident in cells adjacent to irreversibly damaged neurons. In the CA3 region and the hilus of dentate gyrus, HSP 72 was expressed in a few scattered neurons. In septal nucleus, HSP 72 was expressed in a lateral to medial fashion over a period of 1-3 days of recovery. We conclude that severe insulin induced hypoglycemia induces a stress response in neurons in the recovery phase, including inhibition of protein synthesis initiation, depression of eIF-2 activity, and a delayed and prolonged expression of HSP 72 in surviving neurons. The HSP 72 expression may be a protective response to injurious stress. PMID- 8213070 TI - Morphological assessment of ethyl choline mustard aziridinium-induced neurotoxicity in rat brain reaggregate cultures. AB - Foetal rat brain reaggregate cultures have been employed to investigate the morphological changes associated with the neurotoxic action of ethylcholine mustard aziridinium (ECMA). In a companion study we provided evidence for apparent selective cholinergic neurotoxicity. Exposure of 9-day-old cultures to 12.5 microM ECMA for 3 days produced dilatation of selected axon preterminals and terminals in the outer core tissue layer. Axoplasm in these dilated terminals was electron lucent and contained a flocculent, plasma-like material with remnants of the smooth endoplasmic reticulum. Their synaptic vesicle content was much reduced or, absent. Microglial cells were engaged in phagocytosis of these effete structures and a few necrotic neurons were enveloped by glial processes. Exposure to 50 microM ECMA produced widespread necrosis with some surviving neurons, surrounded by the still-persisting capsular layer. Treatment with 100 microM ECMA generated a greater extent of tissue necrosis, with only a few surviving neurons and glial cells being contained within the necrotic tissue mass. Reaggregates frequently disintegrated following capsule loss. Our results indicate that the initial morphological manifestation of ECMA-induced toxicity is dilatation of axon terminals, that are probably of cholinergic origin and are targeted due to their possession of the high-affinity choline transport system which is unique to these neurons. PMID- 8213071 TI - Primary central white matter degeneration in old dogs. AB - Degeneration of the central white matter is described in old dogs. The presence of ubiquitin-immunoreactive free granules and intracytoplasmic globules in glial cells and macrophages, together with galacerebroside-immunoreactive precipitates and lipofusion storage, point to the likelihood of a primary myelin degeneration with deposits of non-degraded ubiquitin-protein conjugates and complex galactolipids. PMID- 8213072 TI - Synaptic stripping in the human facial nucleus. AB - An autopsy case of severe peripheral facial nerve paresis with disconnection of synapses from facial motor neurons is reported. A 77-year-old man presented with left-sided otitis media and subsequent development of facial nerve paresis. Three months later, the patient died of an acute gastrointestinal bleeding from a chronic duodenal ulcer. Gross inspection of the brain revealed non-stenosing arteriosclerotic vascular changes and a single small cystic lesion in the right putamen. Microscopically, marked chromatolytic changes were observed in the left facial nucleus. Immunocytochemistry for synaptophysin revealed a marked loss of afferent synaptic contacts from somatic and stem dendritic surface membranes of all chromatolytic motor neurons. Wrapping of a number of neurons by newly formed glial fibrillary acidic protein-positive astrocytic cell processes could be detected in the regenerating facial motor nucleus. In addition, expression of HLA DR was increased on a small number of microglia and perivascular cells. These changes were absent from the contralateral, normal-appearing facial nucleus. To our knowledge, this case provides the first evidence for disconnection of synapses following peripheral nerve lesioning in humans. Occurrence of synaptic stripping is likely to explain nuclear hyperexcitability and failure of recovery of complex fine motor movements that are commonly observed following peripheral injury to the facial nerve. PMID- 8213074 TI - The intermediolateral nucleus in sporadic amyotrophic lateral sclerosis. AB - Histological and morphometrical observations of the intermediolateral nucleus (IML) at the levels of the upper and lower thoracic segments (T2 and T9) were carried out in 18 patients with sporadic amyotrophic lateral sclerosis (ALS) and 15 age-matched control subjects. Of the 18 ALS patients 6 had been on a respirator before death. No Bunina bodies were found in the IML neurons in either the ALS patients or the control subjects. Only a small number of spheroids were encountered rarely in the IML in both the patients and controls. The number of neurons in the IML in the non-respirator-supported ALS patients were reduced at T2, but well preserved at T9 compared with the control subjects. In the respirator-supported ALS patients, there was a marked reduction of IML neurons at both T2 and T9. Considering the absence of direct synaptic contacts with anterior horn cells, these neurons, without the formation of Bunina bodies, appeared to be involved primarily in the disease process in sporadic ALS. PMID- 8213073 TI - Unusual orthochromatic leukodystrophy with epitheloid cells (Norman-Gullotta): increase of very long chain fatty acids in brain discloses a peroxisomal disorder. AB - Very long chain fatty acids (VLCFA) were found to be markedly increased and phytanic acid was borderline above normal in formalin-fixed brain white matter of case with an unusual type of familial leukodystrophy with epitheloid cells as described previously by Gullotta et al. [Neuropadiatrie (1970) 2: 173-186]. Increased VLCFA in brain clearly demonstrate that the patient had suffered from a peroxisomal disease. This diagnosis is corroborated by ultrastructural findings in brain showing typical lamellar inclusions. The particular type of peroxisomal disorder present in case (heterozygote of X-linked adrenoleukodystrophy?) remains speculative. PMID- 8213075 TI - Sclerosing fibrous tumor of the cauda equina: a fibroblastic variant of peripheral nerve tumors? AB - The case of a 43-year-old man with an unusual mesenchymal tumor of the cauda equina is presented. A well-circumscribed firm tumor was found in the lower spinal canal at L1 level. Although a nerve root was involved, the adjacent dura mater or filum terminale was unrelated to the tumor. Microscopically, the tumor was rich in collagen and made up of irregularly intertwining fascicles of fibroblastic spindle cells lacking in nuclear atypia or mitotic activity. Partial broad hyalinization of collagen was another histological feature of the tumor. Histological and immunohistochemical studies failed to reveal any findings that suggested known fibrous neoplasms, such as schwannoma, neurofibroma and meningioma, originating in the nervous system. Ultrastructural features of the tumor cells were consistent with those of fibroblasts. Hence, the present tumor is regarded as a unique pure fibroblastic tumor (fibroma) derived from the interstitium of a nerve root in the cauda equina. PMID- 8213076 TI - Nephrosialidosis: ultrastructural and lectin histochemical study. AB - The neuropathological findings in a Japanese male with nephrosialidosis are reported. Clinically, coarse face, psychomotor retardation, macular cherry-red spot and proteinuria were noted at 1 year and 7 months. He was diagnosed to have nephrosialidosis on the basis of a deficiency of alpha-neuraminidase activity in both lymphocytes and cultured skin fibroblasts, and of severe glomerular and tubular involvement on renal biopsy. He died of multiple organ failure at 8 years and 6 months. There were numerous vacuoles and storage materials in visceral organs, particularly in the glomerular and tubular epithelial cells of the kidney and Kupffer cells as well as hepatocytes in the liver. Neuropathological examination revealed severe neuronal storage in the selected part of the central nervous system: lower motor neurons of the brain stem and spinal anterior horn cells, as well as neurons in the basal nucleus of Meynert. In the peripheral nervous system, sympathetic ganglia were severely affected. There was little or no neuronal storage in the basal ganglia, cerebral cortex or cerebellum, and demyelination was not found. Electron microscopic examination showed fine wavy multilamellar structures in the spinal anterior horn cells or Zebra body-like structures in the neurons of the Meynert's basal nucleus. Lectin histochemistry was positive for wheat germ agglutinin, Ricinus communis agglutinin-1 and peanut agglutinin within distended neurons. We conclude that the neuropathological feature in nephrosialidosis is not specific except for the selectiveness of the anatomical sites of involvement. It shares some aspects found in other types of sialidosis or galactosialidosis. PMID- 8213077 TI - Paraneoplastic cerebellar degeneration with a circulating antibody against neurons and non-neuronal cells. AB - We describe a woman with paraneoplastic cerebellar degeneration associated with para-ovarian adenocarcinoma, who had a circulating antibody with a corresponding antigen not only in cerebellar Purkinje cells but also in neurons located in the molecular layer of the human and rat cerebellum. The antigen was also present in neurons in the cerebral cortex, brain stem, anterior horn cells, dorsal root ganglia, intestinal autonomic neurons, retinal ganglion cells, Schwann cells of the peripheral nerve and epithelial cells of the renal glomerulus in rats. Immunoelectron microscopy revealed immunoprecipitates in the smooth and rough endoplasmic reticulum and polyribosomes in human and rat cerebellar Purkinje cells and other neuronal cell bodies as well as Schwann cells of the peripheral nerve. Even though patients with this disorder manifest primarily with cerebellar and some extracerebellar signs, the antigen also exists in many neurons other than cerebellar Purkinje cells and even in non-neuronal cells. The clinicopathologic significance of the observed immunologic reaction in diverse neurons remains to be determined. PMID- 8213078 TI - Immunotactoid-like endoneurial deposits in a patient with monoclonal gammopathy of undetermined significance and neuropathy. PMID- 8213079 TI - Posterior cortical atrophy in Alzheimer's disease: analysis of a new case and re evaluation of a historical report. AB - Disturbances of visual function are not uncommon in Alzheimer's disease and several cases with complex impairment of visuospatial abilities have been described. For instance, posterior cortical atrophy has been demonstrated in cases displaying Balint's syndrome as the first symptom of the dementing illness. Such cases showed very high lesion counts in the occipital cortex, as well as in visual association regions in the posterior parietal and posterior cingulate cortex, whereas the prefrontal cortex was consistently less severely involved than usually observed in Alzheimer's disease. This suggests that the distribution of the lesions had been shifted to specific elements of the visual system. In the present study, we report the quantitative analysis of a new case of Alzheimer's disease with possible Balint's syndrome and re-evaluate a case originally described in 1945. The distribution of lesion in these two cases parallels previous observations of Alzheimer's disease cases with early visual impairment. Both cases displayed very high densities of neurofibrillary tangles and senile plaques in the primary visual cortex, secondary visual cortex, visual association areas of the dorsal occipital and posterior parietal lobe and in the posterior cingulate cortex, whereas the prefrontal and inferior temporal regions were comparatively less affected. These cases may define clinical subgroups of Alzheimer's disease and suggest that the breakdown of corticocortical projections that is known to occur in dementia may involve select components of specific functional systems in certain cases. In particular, pathways that subserve motion detection and visuospatial analysis appear to be dramatically affected in these cases presenting with Balint's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213080 TI - Neuroaxonal dystrophy in HTLV-1-associated myelopathy/tropical spastic paraparesis: neuropathologic and neuroimmunologic correlations. AB - Detailed neuropathologic and immunohistologic analysis of a case of serologically and polymerase chain reaction-confirmed human immunodeficiency virus type I (HTLV I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is reported in a 73-year-old North American black woman. In addition to the usual neuropathologic features of HAM/TSP, including tractal degeneration of the spinal cord, leptomeningeal and perivascular fibrosis, perivascular demyelination and chronic inflammation, neuroaxonal spheroids were prominent in the spinal cord. Neuroaxonal dystrophy was characterized by neurofilamentous masses that were immunoreactive for phosphorylated neurofilament epitopes, but not ubiquitin. Neuroimmunologic analysis of the inflammatory reaction revealed a prevalence of CD8+ T cells and class I major histocompatibility molecules (MHC) (HLA-ABC and beta 2-microglobulin), but very few CD4+ T cells. Microglia were highly reactive for class II MHC (HLA-DR alpha) and this was attributed to activation, rather than CD4 interaction, since CD4 presence was minimal. Inflammatory cytokine immunoreactivity was also detected in glia. It is concluded that the cumulative effects of cytotoxic T cell (CD8) infiltration and the possible involvement of cytokines were responsible for the unusual degree of neuroaxonal dystrophy and vascular fibrosis, as well as the observed demyelination in this case. PMID- 8213081 TI - Widespread distribution of tau in the astrocytic elements of glial tumors. AB - Recently tau immunoreactivity has been observed in astrocytes in Alzheimer's disease and other neurological diseases. We examined the immunohistochemical localization of tau in 110 human brain tumors. Tau was widely distributed in the glial neoplastic cells and the reactive astrocytes in tumor tissues. In human surgical specimens positive immunostaining for tau was frequently observed in astrocytic tumors, oligodendroglial tumors, and glioblastoma, as well as neuronal tumors. The astrocytic neoplastic cells in medulloblastoma and other poorly differentiated tumors were also stained. In contrast, no immunoreactivity was observed in meningiomas and schwannomas. The expression of tau in brain tumors was mainly restricted to those cells with astrocytic features rather than small immature cells. The expression of tau mRNA was also demonstrated in astrocytic tumors. In conjunction with the findings of tau-positive astrocytes in some degenerative disorders, astrocytes are considered to have a potential to express tau through neoplastic transformation and reactive processes. PMID- 8213082 TI - Smaller number of large myelinated fibers and focal myelin thickening in mutant quails deficient in neurofilaments. AB - The peripheral nervous system of a mutant of a Japanese quail deficient in neurofilaments (mutant) and of a normal Japanese quail (control) was morphometrically evaluated to characterize the morphological findings, especially those of the myelinated fibers of the mutant. In the proximal peroneal nerves, the frequency of the teased myelinated fibers showing the focal myelin thickening was higher in mutant than in control (P < 0.001) without obvious ongoing axonal degeneration and segmental demyelination. The total numbers of the myelinated fibers in the proximal and distal peroneal nerve, and in the tibial nerve branch to gastrocnemius muscle (pars medialis) were similar between control and mutant, although the number of the large myelinated fibers was less (P < 0.01) and the number of the small myelinated fibers was greater (P < 0.01) in mutant compared with control. The median diameters of neuronal cell bodies of the sacral dorsal root ganglia were similar in control and mutant. The percentages of light, dark and unclassified cells evaluated based on the histologic cytoplasmic features were also similar in control and mutant. Therefore, morphometric alterations were more pronounced in the peripheral myelinated nerve fibers compared with those in the cell bodies of the spinal dorsal root ganglia. We concluded that a smaller number of large myelinated fibers with a greater number of small myelinated fibers and the presence of focal myelin thickening are the main morphologic findings in this mutant, probably due to the arrest of radial growth or maturation of the axons of the myelinated fibers in the absence of ongoing myelinated fiber degeneration. PMID- 8213083 TI - Dialysis-associated encephalopathy: light and electron microscopic morphology and topography with evidence of aluminum by laser microprobe mass analysis. AB - Recently we described silver-staining variants for the demonstration of beta/A4 amyloid and neurofibrillary tangles in senile dementia of Alzheimer type (SDAT). The same methods allowed, for the first time, the visualization of characteristic patterns and distinct morphological changes in human dialysis-associated encephalopathy. Light and electron microscopy demonstrated typical silver-stained inclusions in the cytoplasm of choroidal epithelium, glia and neurons. Performing laser microprobe mass analysis on en-bloc silver-stained semithin sections, evidence for significant amounts of aluminum was obtained within the lesions. Prominent aluminum-signals were obtained additionally in adjacent structures and nuclei of sections which were stained with toluidine-blue exclusively. Silver stained paraffin sections of ten patients with a history of long-term hemodialysis were evaluated. The choroidal epithelium--obviously the most sensitive structure--showed black inclusions ranging from a few dots to a complete black staining of cells. Glial cells presented massive silver-stained deposits, which were restricted to the gray matter. Finally, neurons revealed numerous fine-granular black inclusions, scattered throughout the cytoplasm. Brain stem nuclei were primarily affected, but neurons within cortex, subcortical gray matter and spinal cord were also involved to various degrees; inclusions were not evident in the nucleus dentatus and the oliva inferior. Vessel-related deposits were found frequently. By electron microscopy the cytoplasm of neurons was filled either with large amounts of small electron-dense granules, or with lipofuscin granules, containing numerous irregular, non-membrane-bound inclusions. Massive electron-dense depositions were seen in the cytoplasm of choroidal epithelia and in proximity to nuclei of cortical astro- and oligodendroglia. The described neuronal changes and, in particular, alterations of choroidal epithelium and glia are completely different from characteristic plaques and tangles in SDAT. PMID- 8213084 TI - Vascular dementia in Spatz-Lindenberg's disease (SLD): cortical synaptophysin immunoreactivity as compared with dementia of Alzheimer type and non-demented controls. AB - The generalized form of von Winiwarter-Buerger's disease (WBD) occasionally involves the brain. However, pure cerebral forms of the disease were also described by Spatz and Lindenberg ("Spatz-Lindenberg's disease", SLD). Both, the type I, which involves the large basal arteries, and the type II, which results in a sickle-shaped granular atrophy of the cerebral cortex, are often accompanied by ("vascular") dementia, which Lindenberg and Spatz mainly attributed to the bilateral involvement of the second frontal gyrus by granular atrophy. Recently, synaptic deprivation of the cortical gray matter has been shown to occur in the dementia of Alzheimer type (DAT) and other neurodegenerative disorders. In DAT, the synaptic loss highly correlated with the degree of the mental impairment. We wanted to examine whether similar changes also occurred in dementia of vascular origin, for which SLD, although infrequent, is a typical example. In fact, we found that in three cases of typical SLD type II the synaptophysin immunoreactivity of the cortical neuropil in areas without overt infarcts or scar formation was as much reduced as in Alzheimer's disease. Although it must be taken into account that in the present cases the synapse loss might, at least in part, be due to secondary (Wallerian) degeneration as a result of the neuronal loss in the "watershed" regions of the arterial blood supply, it cannot be excluded that a decline of cortical synaptic contacts in areas without necroses or scars may occur as a primary event, contributing to the pathogenesis of the dementia. Final conclusions can only be expected from investigations into further cases of cerebro-vascular disorders with and without dementia. PMID- 8213085 TI - Neurofibrillary tangles of Guamanian amyotrophic lateral sclerosis, parkinsonism dementia and neurologically normal Guamanians contain a 4- to 4.5-kilodalton protein which is immunoreactive to anti-amyloid beta/A4-protein antibodies. AB - Neurofibrillary tangles (NFT), one of the neurodegenerative features of Alzheimer's disease, Down's syndrome and normal aging, is a constant, widespread neuropathological finding in Guamanian amyotrophic lateral sclerosis (ALS), parkinsonism-dementia (PD) and in neurologically normal Guamanians, dying of causes other than ALS and PD. NFT in brain tissue sections of patients with Guamanian ALS and PD were immunoreactive to antibodies directed against a 43 amino acid synthetic peptide homologous to amyloid beta/A4-protein (anti-SP43) associated with Alzheimer's disease. NFT extracted from frozen brain tissues of Guamanian patients with ALS and PD and from tissues of neurologically normal Guamanians were congophilic and birefringent. By negative-stain electron microscopy, NFT preparations contained bundles and/or isolated single, straight, unpaired filaments in Guamanian ALS and occasionally pairing of filaments in neurologically normal Guamanians, measuring 5-20 nm in diameter. Formic acid digestion of NFT preparations, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and size-exclusion high-pressure liquid chromatography, showed a protein with an apparent molecular mass of 4- to 4.5-kDa, which by Western blot analysis was immunoreactive to anti-SP43. Immunoabsorption of purified NFT or SP43 with anti-SP43 abolished immunostaining. Our study corroborate previous data that amyloid beta/A4-protein is present in NFT in Guamanian PD. Furthermore, our data indicate that amyloid beta/A4-protein is present in NFT in brain tissues of patients with Guamanian ALS and in neurologically normal Guamanians, suggesting a common mechanism of amyloidogenesis with NFT formation in Alzheimer's disease and normal brain aging. PMID- 8213086 TI - CD24, a signal-transducing molecule expressed on human B lymphocytes, is a marker for human regenerating muscle. AB - The expression of the CD24 molecule, a glycoprotein expressed at the surface of most B lymphocytes and differentiating neuroblasts, was studied in developing nerve and muscle (after 16 weeks of gestation), normal adult and various diseased human muscles using immunohistochemistry and Western blot analysis. Immunohistochemical studies demonstrated that: (1) in developing muscles, fibers did not express CD24, whereas only some mesenchymal areas, also expressing neural cell adhesion molecule (N.CAM) and vimentin, and developing nerves were positive; (2) in normal adult muscles, CD24 immunoreactivity was observed only in some unmyelinated nerve fibers--intra and extra fusal muscle fibers, satellite cells and neuromuscular junctions were negative; and (3) in all diseased muscles studied here, CD24 expression was always associated with a subpopulation of regenerative fibers. These fibers also expressed vimentin, desmin, developmental myosin heavy chain, N.CAM and its polysialylated isoforms (PSA-N.CAM). The number of CD24-positive fibers was always lower than that of PSA-N.CAM-positive fibers. Denervated fibers and vacuolated muscle fibers never expressed CD24. Western blot analysis indicated that the apparent molecular mass of CD24 antigen was different between muscle and developing nervous tissues, suggesting that CD24 glycosylation is tissue specific. Since the molecule was not expressed in developing human muscle fibers, it strongly suggests that regenerative and fetal myotubes are different with respect to the CD24 molecule expression. PMID- 8213087 TI - Central nervous system Strongyloides stercoralis in acquired immunodeficiency syndrome: a report of two cases and review of the literature. AB - Hyperinfection with Strongyloides stercoralis is rare in acquired immunodeficiency syndrome (AIDS), despite endemicity in areas where infection with human immunodeficiency virus is highly prevalent. We autopsied two patients with AIDS and disseminated Strongyloides and describe their central nervous system findings. The microscopic patterns of brain infection were dissimilar in the two patients, and reflected histology in systemic viscera. In one patient, a granulomatous response accompanied filariform larvae in all locations, including granulomatous ependymitis in brain. Additionally in the brain, larvae without tissue reaction were seen. In the second patient, the absence of tissue response to larvae was body wide, and isolated parasites were found in centrum semiovale. The occurrence of these patients in a region where Strongyloides is not endemic suggests that this infection may be more prevalent in AIDS than formerly suspected. PMID- 8213089 TI - Ultrastructural characteristics of glial fibrillary acidic protein expression in epoxy resin-embedded human brain tumors. AB - Thirteen surgically removed, epoxy resin (Durcupan ACM or Epon 812)-embedded human brain tumors were examined for glial fibrillary acidic protein (GFAP) content in semithin and ultrathin sections with the immunogold-silver staining method. Mild aldehyde fixation and the hydrophobic resin embedding did not interfere with the antigenicity, since silver intensification of the immunogold marker provided excellent visualization of the reaction on both light microscopic and ultrastructural levels. The GFAP reaction was usually localized on the glial intermediate filament bundles, usually correlating well with the amount of filaments. The unstained filamental regions of two ependymomas might correspond to the vimentin expression revealed by double labeling in semithin sections. Occasional GFAP immunopositivity without filamental appearance was observed in one of the oligodendrogliomas, as patchy electron-dense cytoplasmic corpuscules, in Rosenthal fibers and in some mainly necrobiotic tumor cells, reflecting a possible connection with glial filaments. PMID- 8213088 TI - Histological features of axial structures during embryonic and fetal stages of human craniorachischisis. AB - Histological characteristics of developing axial structures in human conceptuses with craniorachischisis were investigated during the embryonic and fetal periods and compared with normal samples. The morphological relationship of the notochord to the axial skeleton and neural tube was analyzed along cervical and thoracic vertebral segments using serial paraffin sections. The embryonic stage of malformed conceptuses disclosed a correlated affection of the notochord and vertebral column, as well as the overlying central nervous system. The degree of histological changes within the spinal cord depended on the level of the vertebral axis examined: completely unorganized nervous tissue was overlying cervical and upper thoracic vertebrae, while more caudally it resembled a normal spinal cord. During the fetal period the histological disturbances of all axial structures were more pronounced. Extensive notochordal branching was associated with the malformed formation and ossification of the vertebral column. At this stage we found no correlation of histological changes between the spinal cord and the mesodermally derived structures (notochord, vertebral column) along the cranio-caudal body extent, as neural tissue had completely transformed into area cerebrovasculosa. We speculate that our histological observations could be the result of primary affection of mesodermal structures during very early stages of development. Divergence in histological findings within axial structures between the embryonic and fetal periods support recent mutational investigations on animals. PMID- 8213090 TI - Distinct neuronal subset reveals perikaryal immunostaining for synaptophysin (protein p38) in the striatum of rats. AB - An immunoperoxidase technique was used to locate synaptophysin (protein p38), a major integral membrane glycoprotein of synaptic vesicles, in the rat brain. In addition to a diffuse distribution of nerve terminal stainings for synaptophysin appearing as numerous small puncta, the large-sized cells with spindled or polygonal shapes revealed perikaryal staining for synaptophysin in the striatum. The double labeling with immunofluorescence technique disclosed that the cell bodies, immunoreactive for synaptophysin, appeared to be those of the striatal giant cholinergic neurons. In addition, in rats that underwent the transient middle cerebral artery occlusion, the striatal ischemic lesions with cell type specific injury revealed a survival of synaptophysin-positive large cells, presumably identical with the cholinergic neurons. The present study suggests that the metabolism and/or axonal transportation of synaptophysin of the giant cholinergic cells may be different from those of other neuronal populations in the striatum. Also, synaptophysin can act as a neurochemical marker for identification of the giant cholinergic neurons in the striatum of rats. PMID- 8213092 TI - African overture. Malaria on the increase. PMID- 8213091 TI - Adult-onset lysosomal storage disease in a Schipperke dog: clinical, morphological and biochemical studies. AB - An adult-onset lysosomal storage disorder was diagnosed in a 5-year-old Schipperke dog with progressive cerebellar and central vestibular signs. It was characterized by cerebellar atrophy with extensive loss of Purkinje and granular cells, and hydrocephalus. Enlarged and vacuolated neurons were observed in spinal cord and brain; pancreatic centrolobular and islet cells were also vacuolated. Ultrastructurally, enlarged secondary lysosomes laden with lamellated membrane structures were present in neurons and empty enlarged vacuoles were found in pancreatic centroacinar, ductal, and islet cells. On frozen sections neurons stained with Ricinus communis agglutinin-I and wheat germ agglutinin. On paraffin sections neurons stained with luxol fast blue, periodic acid-Schiff, Concanavalia ensiformis agglutinin, and were autofluorescent. These findings indicate an accumulation of glycolipids containing terminal beta-galactosyl and alpha-sialyl residues, and N-linked oligosaccharides. Tissue activity of lysosomal beta galactosidase was 50% of normal and the activity of beta-hexosaminidase was elevated. Brain lipid-bound sialic acid was twice normal, with a small increase of GM1-ganglioside, but there was a significant elevation of GM2 (GD2) and GM3 (GD3). In addition, significant elevations of sialylated and non-sialylated oligosaccharides were noted. These clinical, biochemical and pathological findings are similar to those observed in human patients with adult-onset galactosialidosis. PMID- 8213093 TI - Fetal fibronectin and preterm birth. PMID- 8213094 TI - Calcium homeostasis in pregnancy and lactation. AB - This paper discusses different aspects of calcium homeostasis in pregnancy: the calcium demands of the mother, regulation mechanisms and the risk factors for demineralization. Special care should be paid to patients lying in bed for long periods and patients given heparin prophylaxis. One to two grams of calcium and 400 IU of vitamin D daily should be given orally to patients who are being treated for deep vein thrombosis. In addition, bone density should be checked to detect osteoporosis. The period of heparin prophylaxis must be as short as possible and bed rest must not be unnecessarily prolonged. PMID- 8213095 TI - Lithium stimulates the first meiotic division in mouse oocytes. AB - Cumulus enclosed oocytes, cumulus enclosed oocytes denuded of their cumulus and cumulus free oocytes from 21 day old unstimulated mice were cultured for 18 hours in control medium supplemented with lithium chloride, dbcAMP and forskolin at various concentrations. In control medium 66% of the cumulus enclosed oocytes, 93% of the denuded oocytes, and 94% of the cumulus free oocytes resumed meiosis (germinal vesicle breakdown), whereas the levels of polar body formation were 27%, 12% and 39%, respectively. In the presence of lithium significantly more cumulus enclosed oocytes and cumulus free oocytes resumed meiosis and formed a polar body, whereas lithium had no effect on the denuded oocytes. Forskolin and dbcAMP stimulated resumption of meiosis and cumulus expansion in the cumulus enclosed oocytes and inhibited resumption of meiosis in the cumulus free oocytes. Lithium more or less eliminated this inhibitory effect of both forskolin and dbcAMP in the cumulus free oocytes. The results indicate (i) that activation of the cAMP second messenger path in the cumulus cells induces them to synthesize a meiosis inducing substance(s) which stimulates the oocyte to resume meiosis, and (ii) that other second messenger systems than the cAMP pathway, e.g. the phosphatidylinositol cycle, are involved in resumption of meiosis and polar body formation. We conclude that lithium enhances the capability of mouse oocytes for resumption of meiosis and polar body formation. PMID- 8213096 TI - The amnion produces little of the prostaglandin E2 detected on the decidual side of human fetal membranes. AB - Cultured intact fetal membrane disks initially produced high levels of prostaglandin E2 (PGE2) on the fetal and maternal sides which declined during four days of culture. The transfer of a bolus of PGE2 from the fetal side to the maternal side of the membrane ranged from 1% to 3% after 24 hours of culture, and was a minimum over the period of 48-72 hours from the start of the incubation. To assess the handling of PGE2 synthesized by the amnion, 3H-arachidonic acid was incorporated into cultured amnion and into the amnion side of cultured intact fetal membrane disks. Labelled amnion released 3H-PGE2 on both sides of the tissue, whereas similarly labelled cultured intact fetal membrane only had detectable levels of 3H-PGE2 on the fetal side. It was calculated that no more than 9.7 +/- 1.4% of the PGE2 synthesised by the amnion crossed to the maternal side of the membrane without being metabolised during the transfer through the membrane. These results are consistent with similar indirect methods which suggested that PGE2 from the amnion may have only a limited role in human labor, and indicates the importance of using appropriate culture systems to investigate intra-uterine prostaglandin production. PMID- 8213097 TI - The effect of magnesium sulfate on maternal and fetal blood flow in pregnancy induced hypertension. AB - The purpose of this study was to evaluate the effects of magnesium sulfate on maternal and fetal blood flow in pregnancy-induced hypertension. Twelve patients with pregnancy-induced hypertension were prospectively studied with transcranial pulsed Doppler and transabdominal color flow Doppler before and after infusion of a 6 gram intravenous loading dose of magnesium sulfate. The maternal vessels studied included the middle cerebral, common carotid, and internal carotid arteries. The fetal vessels studied included the middle cerebral, renal, and umbilical arteries. In addition the maternal circulation in the placental base plate was imaged. The results of this descriptive study suggest that a 6 gram loading dose of magnesium sulfate significantly vasodilates the vascular bed distal to the maternal middle cerebral artery, and increases blood velocity in this distribution. There was no significant change in pulsatility index or blood velocity in the central large vessels of the head and neck. There were no acute effects noted in the fetal or placental vessels evaluated. PMID- 8213098 TI - The prognosis of hypertensive disease of pregnancy accompanied by intrauterine growth retardation in relation to parity. AB - Twenty-two primiparous women with hypertensive disease of pregnancy (HDP) associated with intra uterine growth retardation (IUGR) were compared with 20 parous women in whom HDP associated with IUGR appeared for the first time in a second or a later pregnancy. Both groups of women were followed up for 10-13 years. The course of the disease among the parous women was more severe as compared to the primiparous women; the mean gestational age at the first increase in blood pressure and gestational age at delivery were significantly earlier in the parous group (33.3 weeks +/- 3.5 v.s. 35.3 +/- 3.2 weeks, p < 0.01, 36.2 weeks +/- 2.2 v.s. 37.6 +/- 1.9 p < 0.01 accordingly). Maternal indication for induction of labor because of uncontrollable hypertension was present in 77% of the cases in the parous group as compared to 31% in the primiparous group (p < 0.05). These complications were present in 66% of subsequent pregnancies in the parous group as compared with 31% in the primiparous group (p < 0.05). Chronic hypertension developed in 33% of the parous group as compared with 20% in the primiparous group. These differences show that the manifestation of HDP is more severe in women in whom HDP with IUGR occur for the first time in a second or a later pregnancy than in those in whom this complication occurs for the first time in a second or a later pregnancy than in those in whom this complication occurs for the first time in their first pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213099 TI - Relationship between iron status in pregnant women and their newborn babies. Investigation in a Spanish population. AB - We studied 157 pregnant women living in Merida, Spain, during their third trimester of pregnancy and their newborns at birth, analyzing the mother's and the umbilical cord's blood for hemoglobin, hematocrit, mean corpuscular hemoglobin concentration (MCHC), serum iron and serum ferritin. We observed statistically correlations between hemoglobin and hematocrit values of the mother with erythrocyte count, hemoglobin and hematocrit values of her child and between serum iron of mother and child. The blood levels in the umbilical cord did not decrease until the ferritin value of the mother was < 12 micrograms/l. Under these conditions the ferritin levels in the umbilical cord blood (80.4 micrograms/l) were significantly lower than in those newborn infants whose mother had adequate ferritin levels (123 micrograms/l). We deduce that maternal iron status seems to condition, at least partially, fetal iron status, specially when the mother has some deficiencies. We did not find a lower birth weight in children of anemic mothers. Actually, we found an inverse correlation between maternal hemoglobin values and infant birth weight (r = -0.1731, p < 0.05). It is possible that the demands on the mother are increased in the case of a newborn infant of greater size. PMID- 8213100 TI - Meconium stained amniotic fluid is associated with maternal infectious morbidity in pre term delivery. AB - The purpose of the study was to determine if intra partum meconium stained amniotic fluid (MSAF) is associated with infectious morbidity in women with pre term delivery. The study group was composed of 89 women with pre term delivery and MSAF. The control group comprised 89 women with pre term delivery and clear amniotic fluid, matched for maternal age, gravidity, parity, gestational age, rate of premature rupture of membranes, breech presentation and mode of delivery. The parameters of maternal infectious morbidity were compared between the two groups during pregnancy, delivery and puerperium. The prevalence of recurrent urinary tract infections was significantly higher in the study group than those in the control group, 7.8% (7/89) vs. 0% (0/89), respectively (p = 0.02). During delivery women with MSAF had a significantly higher rate of clinical chorioamnionitis than women without MSAF, 6% (6/89) vs. 0% (0/89), respectively (p = 0.03). Histological chorioamnionitis was also significantly higher in patients with intra partum MSAF, as compared to those the clear amniotic fluid, 11.2% (10/89) vs. 0% (0/89), respectively (p = 0.03). In addition, women in the study group had a significantly higher post partum infectious morbidity rate and endometritis than women in the control group [52.8% (47/89) vs. 37.1% (33/89) (p = 0.05); 18% (16/89) vs. 7.8% (7/89) (p = 0.03), respectively]. We conclude that intra partum MSAF should be considered as a potential marker for infectious morbidity in women with pre term labor and delivery. PMID- 8213101 TI - Maternal and neonatal C-reactive protein after interventions during delivery. AB - To evaluate the effects of interventions during delivery on the maternal and neonatal C-reactive protein (CRP) we prospectively measured CRP by immunoturbidometry in 238 mother-infant pairs (179 normal vaginal deliveries, 36 cesarean sections and 23 vacuum extractions) at 24 and 72 hours after delivery. We additionally measured CRP in peripheral maternal and neonatal blood immediately after birth in 29 uncomplicated vaginal deliveries. CRP values in the mothers and their offspring were low at birth, but rose significantly during the first day after vaginal delivery. Cesarean section induced a pronounced elevation of maternal CRP, but had no effect on neonatal values. Delivery by vacuum extraction produced a transient elevation of both maternal and neonatal CRP at 24 hours after birth. Neonatal CRP values were not associated with presence or size of superficial birth tissue trauma evaluated simultaneously with blood sampling. Increased CRP release in mothers and their infants after interventions during delivery may be associated with varying degrees of tissue trauma and can complicate assessment of the presence of infection. PMID- 8213102 TI - Fertility outcome after treatment of tubal pregnancy by laparoscopic laser surgery. AB - In 150 women with tubal pregnancy consecutively treated over a two year period by laparoscopic techniques, 74 were treated conservatively by linear salpingotomy with carbon dioxide laser laparoscopy and 76 cases non-conservatively through the laparoscope by salpingectomy. Between 15 and 37 months later all patients were contacted by means of questionnaires to evaluate subsequent fertility outcome. Sixty-six percent (38/58) of those women who desired pregnancy after conservative laparoscopic treatment achieved an intrauterine pregnancy. The corresponding rate for women who desired pregnancy after salpingectomy was 45% (18/40). The recurrent ectopic pregnancy rates in the two groups were 7% (4/58) and 10% (4/40), respectively. This study confirms that tubal pregnancy can be appropriately managed by laparoscopic laser surgery with the advantages of minimal invasive techniques. PMID- 8213103 TI - Effect of norethisterone and levonorgestrel in low-dose multiphasic oral contraceptives on serum lipids. AB - In a parallel, multicenter study in Norway and Finland involving a total of 196 healthy women (mean age 22.4 years, range 18-30), the effects on serum lipids and lipoproteins of two multiphasic oral contraceptives containing ethinyl estradiol (EE) but different progestins were examined. One formulation contained EE 35 micrograms and norethisterone (NET) 0.5 mg on days 1-7 and days 17-21 and elevated NET 1.0 mg during the midphase (days 8-16). The other formulation contained EE 30 micrograms on days 1-6 and days 12-21 and 40 micrograms on days 7 11 and phased levonorgestrel (LGN): 50 micrograms (days 1-6), 75 micrograms (days 7-11) and 125 micrograms (days 12-21). Both formulations induced significant elevation of total cholesterol (6.7 and 4.1%), Apo B (8.1 and 7.0%) as well as HDL (6.4 and 3.7%) for the EE/NET and EE/LGN formulation respectively. Mean serum levels of triglycerides were significantly elevated (58 and 47%). However, all mean serum lipid and lipoprotein values remained within the normal range, and no change in the calculated cholesterol ratio (HDL/total cholesterol) nor lipoprotein ratio (HDL/(HDL+LDL)) was observed. No significant difference between the formulations could be detected with respect to the effect on serum lipids and lipoproteins measured. The change in total cholesterol was smaller than reported in many studies of monophasic preparations. Taken together, these data suggest that only small alterations in lipid metabolism are elicited by these oral contraceptives. PMID- 8213104 TI - No effect of single dose ofloxacin on postoperative infection rate after first trimester abortion. A clinical, controlled trial. AB - In a double-blind stratificated, placebo controlled study the efficacy and safety of a single oral dose of ofloxanin (Tarivid) (400 mg) in preventing postabortal pelvic inflammatory disease (P-PID) in women with induced first-trimester abortions were assessed. The tablets were given 1 1/2-2 h before the abortion, and the women were followed one month after the operation. Group I consisted of 308 with previous PID. Ofloxacin tablets were given to 149 women and 159 women received placebo tablets. In the ofloxacin group 20 women (13.4%) and in the placebo group 27 women (17%) developed P-PID, a non-significant difference (p = 0.39). Group II consisted of 765 women without a history of PID. Ofloxacin tablets were given to 376 women and 389 women received placebo tablets. Thirty five women (9.3%) in the ofloxacin group and 46 women (11.9%) in the placebo group developed P-PID, a non-significant difference (p = 0.26). A single oral dose of ofloxacin (400 mg) did not reduce the incidence of P-PID either among women with previous PID or among women without previous PID. PMID- 8213105 TI - The familial risk of endometriosis. AB - OBJECTIVE: To study the occurrence of endometriosis or adenomyosis in mothers and sisters of patients with endometriosis. METHODS: A total of 563 patients with endometriosis were interviewed about endometriosis or adenomyosis in their mothers or sisters. Five hundred and twenty-eight patients (94%) gave information about their relatives. Six patients were adopted and had no knowledge about their relatives. Among 522 patients were seven pairs of sisters, of which only one was included, giving a total of 515 cases. The control group consisted of 149 women without endometriosis documented at a recently diagnostic laparoscopy performed in connection with sterilization. The controls were likewise interviewed about their relatives, and none refused to give information. If a gynecological operation in a relative was reported, medical records were obtained (68%) or a description of the medical history was given by the proband. RESULTS: Endometriosis or adenomyosis was disclosed in 3.9% of mothers of cases and in 0.7% of mothers of controls, in 4.8% of sisters of cases and in 0.6% of sisters of controls. The relative risk of endometriosis in a first-degree relative (expressed as odds ratio), was 7.2 (95% confidence interval 2.1, 24.3). Severe manifestations of endometriosis were found more often among patients with a positive family history than among those without (26% versus 12%, p < 0.01). CONCLUSION: The study demonstrates a seven fold increased risk of endometriosis in mothers and sisters of patients with endometriosis. It is assumed that daughters of patients with endometriosis have a similar risk of developing endometriosis. PMID- 8213106 TI - Progesterone receptor content in endometrial carcinoma correlates with serum levels of free estradiol. AB - OBJECTIVE: To study a possible relationship between serum levels of estrogens and androgens and the tumor content of estrogen receptors and progesterone receptors in endometrial cancer. STUDY DESIGN: Fifty postmenopausal patients were included. Receptors were determined biochemically in tissue cytosol by dextran charcoal coated assay and immunohistochemically on frozen sections. Serum sex hormones were measured by radioimmunoassays. MAIN FINDINGS: Tumor biochemical progesterone receptor content correlated positively (p < 0.05) with free estradiol serum levels. No correlations were observed between estrogen receptor content and any of the serum sex hormones. The progesterone/estrogen receptor ratio, calculated from the biochemical values, correlated positively (p < 0.05) with the serum levels of free estradiol. This relation was not affected by tumor histologic grade or stage. Furthermore, this ratio correlated positively with body mass index, probably reflecting a correlation between body mass and serum estrogens. Biochemical and immunohistochemical receptor values were correlated. CONCLUSIONS: These findings suggest that hormonal regulation of receptor levels may remain preserved in at least some endometrial cancer cells. PMID- 8213107 TI - Complications after hysterectomy. A Danish population based study 1978-1983. AB - We studied complications after hysterectomy among all women in the Danish population who had a simple hysterectomy in the period 1978-81 based on data obtained from the Danish National Hospital Registry. Among patients, with neither diagnosed cancer nor major co-surgery (n = 23,386), we identified all the complications which occurred during hospital admission from the time of surgery up to six years from that point. Within 30 days of hysterectomy 2.6% of the patients had been diagnosed in hospitals as having complications according to our definition. The corresponding figures at 90 days and two years after the operation were 3.7% and 9.4%. The most frequently observed complications were post operative wound infections and bleeding, each affecting about 2% of all operated women. Logistic regression and Cox regression were used to identify prognostic indicators of readmission with complications. The probability of readmission with complications within six years after hysterectomy was estimated at 8% among low risk patients. The most pronounced increase in risk of readmission with complication occurred among women who had been admitted to psychiatric or somatic hospitals 0-12 months before they had their uterus removed (OR in the range 1.59 to 1.83). We discuss the prevailing difficulties of comparing observational evidence from different clinical settings reported in the literature, and emphasize the importance of developing a coordinated international strategy for non-experimental assessment of medical technology. PMID- 8213109 TI - Pregnancy in a non-communicating uterine horn mimicking incarceration with sacculation of a retroflexed uterus. AB - Incarceration and sacculation of a retroflexed gravid uterus is relatively benign, in contrast with pregnancy in a rudimentary uterine horn which can lead to perforation and hemorrhage. We report a case of pregnancy in an incarcerated sacculated non-communicating rudimentary horn mimicking incarceration with sacculation of a retroflexed gravid uterus. Both physical and sonographic findings were unhelpful in the differential diagnosis. Therefore, decision for laparotomy in such cases should be based on severity of symptoms. PMID- 8213108 TI - Embryonal reduction using transvaginal saline injection in a sextuplet pregnancy after ovulation induction with human menopausal gonadotropin. AB - A sextuplet pregnancy occurred in a first treatment cycle of ovulation induction with human menopausal gonadotropins. The serum 17-beta-estradiol concentration was 1245 pg/ml on the day of human chorionic gonadotropin administration. Embryonal reduction of four fetuses was carried out at nine weeks gestation using a transvaginal ultrasound-guided approach. Under general anesthesia, a 16-gauge in vitro fertilization needle was introduced through the posterior fornix and uterine wall, into the nearest gestational sac. The embryo was penetrated and 0.9% saline solution was injected until disintegration was noted, and confirmed by a lack of pulse for more than two minutes. The same procedure was applied to the three embryos in closest proximity to the needle. The patient delivered healthy twins in the 34th week of gestation after having had pre-term contractions for two weeks. PMID- 8213110 TI - Difficulties in the antenatal assessment of neonatal alloimmune thrombocytopenia. AB - In this paper we present a patient with an initially questionable history of neonatal alloimmune thrombocytopenia (NAT) due to materno-fetal HPA-1a (PLA1) incompatibility. No circulating antibodies were detectable in untreated maternal serum, but an adsorption/elution technique enabled the demonstration of the platelet-specific anti-HPA-1a (anti-PLA1) in maternal serum. Cordocentesis at 35 weeks of gestation revealed a fetal platelet count of 18 x 10(9)/l. Intrauterine platelet transfusion with HPA-1a (PLA1)-negative donor platelets was performed prior to cesarean section. PMID- 8213111 TI - Metastasis from breast lobular carcinoma to an endometrial polyp. Report of a case with immunohistochemical study. AB - A case of lobular carcinoma of the breast metastatic to an endometrial polyp is described. The patient underwent a simple mastectomy and axillary lymphadenectomy because of infiltrating lobular carcinoma diagnosed three years before. Abdominal ultrasound revealed an endometrial polyp. An endometrial biopsy was performed but only scanty material insufficient for diagnosis was obtained. A total hysterectomy and bilateral salpingo-oophorectomy was made. The uterus contained a large polyp which microscopically showed sheets and ribbons of small atypical cells infiltrating the stroma. Immunohistochemical stains were positive for epithelial cell markers. To our knowledge this is the first case of an infiltrating lobular carcinoma metastasizing to an endometrial polyp. PMID- 8213112 TI - Accessory spleen presenting as adnexal mass. AB - Pelvic splenic ectopia is a very rare entity, often unsuspected preoperatively. We report a case of an ectopic spleen presenting as an adnexal mass in a middle aged woman. Diagnosis was achieved intraoperatively, and confirmed pathologically. Pelvic ectopic spleen should be considered in the differential diagnosis of adnexal masses. PMID- 8213113 TI - Ultraviolet blood autotransfusions and plasmapheresis in preeclampsia. PMID- 8213114 TI - Wear of the polyethylene acetabular cup. Metallic and ceramic heads compared in a hip simulator. AB - Ultra-high molecular weight polyethylene acetabular cups of 5 different total hip systems (Muller, Mallory-Head, Lubinus, P.C.A. and Charnley-Elite) were worn on a new 5-station hip joint simulator. The cups articulated against modular metallic (stainless steel in Muller and Charnley-Elite, ion-implanted Ti-6Al-4V in Mallory Head, and Co-Cr-Mo in Lubinus and P.C.A.) and modular alumina ceramic femoral heads for 3 million walking cycles. The mean wear rate of cups against alumina heads (range 0-5.7 mg/10(6) cycles, corresponding to 0-0.008 mm/year) was usually lower than against metallic heads (range 3.9-178 mg/10(6) cycles, corresponding to 0.005-0.24 mm/year). In the metal-head prostheses, the mean wear rate was highest against stainless steel heads, and lowest against ion-implanted Ti-6Al-4V heads. As the wear rates are compared with published clinical observations, it can be concluded that the hip joint simulator is capable of producing realistic wear rates; it is a useful instrument in the study of the wear behavior of new designs, materials, surface treatments and coatings prior to clinical trials. However, the taper-fit attachment of modular heads proved problematical, showing corrosion and wear at the conical head-spigot interface. PMID- 8213115 TI - Failures after revision hip arthroplasties with threaded cups and structural bone allografts. Loosening of 13/18 cases after 1-4 years. AB - Uncemented threaded, smooth cup acetabular components and structural deep-frozen bone allografts harvested from femoral heads during arthroplasties were used for reconstruction of the acetabulum in 18 revision hip arthroplasties. Autogenous bone grafts were also used in every case. The mean follow-up time was 2.5 (1-4) years. Loosening of the prosthetic component occurred in 13 cases. In 8 cases revision of the acetabular component has already been performed, and 5 cases remain to be reoperated. The use of uncemented, threaded cups in combination with reconstruction of bone defects with structural allografts cannot be recommended in acetabular revisions. PMID- 8213116 TI - Prediction of fixation failure in femoral neck fractures. Comminution and avascularity studied in 40 patients. AB - We performed 99m-Tc diphosphonate scintimetries in 40-elderly patients who had undergone screw fixation for a recent subcapital femoral fracture and analyzed their preoperative radiographs. The data were subjected to a logistic regression analysis. Both comminution of the calcar femorale and reduced scintimetric uptake were predictive for failure of the osteosynthesis during the first year. Fracture comminution was more predictive for early failures during 3 months and scintimetry for the later failures. PMID- 8213117 TI - Femoral remodeling after arthroplasty of the hip. Prospective randomized 5-year comparison of 120 cemented/uncemented cases of arthrosis. AB - We compared radiographically the femurs for 5 years after cemented (Landos Titane) and uncemented (Zweymuller/Endler) hip arthroplasty (THA) for coxarthrosis in 120 patients. The bone changes followed a characteristic time course with rapid initial remodeling and almost no further changes after 3-4 years. No association between bone changes and clinical results was found. The groups did not differ in bone atrophy and ectopic bone formation, whereas the incidence of distal cortical hypertrophy and proximal radio-opaque double line was higher around uncemented stems. The age and body weight of the patients and the stem size did not affect the bone changes, but women with uncemented stems developed more bone atrophy than did men. PMID- 8213118 TI - Closed suction drainage after hip arthroplasty. Prospective study of bacterial contamination in 81 cases. AB - In a prospective study we analyzed the volume of drainage, the contamination of the drain track, and drain tip in 81 primary total hip arthroplasties in 78 patients. The drain was removed when the drainage from midnight to the following morning was 20 mL or less. The drainage in the first 12 h and in total was reduced in cases with a drain period of 24 h, compared to cases with a drain period of 48 and 72 h. 4 cases had a positive culture from the wound before closure. 5 cases had a positive culture from the tip of the drain, and 6 from the drain track. The most frequently isolated microorganism was coagulase-negative Staphylococcus. The positive cultures from the drain track and tip were not correlated to the duration of drainage. 68 drains were removed within 48 h with no risk of developing wound complications. PMID- 8213119 TI - Total condylar arthroplasty for gonarthrosis. A prospective 10-year study of 138 primary cases. AB - The results of 138 consecutive primary Insall-Burstein arthroplasties with an average observation period of 10 (9-11) years were assessed. Mean age at surgery was 71 (30-81) years. The patients were evaluated clinically, using the Hospital for Special Surgery knee rating scale, and radiographically, according to the radiolucency score of the Knee Society. At latest follow-up, the overall evaluation of the patients who completed the study was excellent or good in 86 percent, fair in 8 percent and poor in 6 percent. Residual functional pain was recorded in 12 percent of cases with prostheses in situ. An ability to walk more than 500 m was found in 62 percent. The median range of motion was 104 degrees. Arthrodesis was performed on 2 knees due to deep infection. There were 14 cases with substantial radiolucency around the prosthesis, but none of these patients had severe functional pain. The crude prosthetic survival rate was 98 percent. A correlation was found between the radiolucency score and both the total score and the intensity of the residual functional pain. PMID- 8213120 TI - Revision of the PCA unicompartmental knee. 52 arthrosis knees followed for 2-5 years. AB - We evaluated 52 unicompartmental PCA arthroplasties for primary (46) or secondary (6) arthrosis after 3 (2-5) years. Cementless fixation was used in 35 femoral and in 28 tibial components. There were indications for revision in 11 cases. Conversion to a total knee had been performed in 4 cases, and 1 tibial as well as 1 femoral component had been exchanged, mainly because of polyethylene wear with increasing deformity. 2 femoral components were loose and 1 had fractured. PMID- 8213122 TI - Osteochondral lesions and cruciate ligament injuries. MRI in 18 knees. AB - Magnetic resonance images were obtained prior to arthroscopy and surgery in 18 knees with acute anterior cruciate ligament injury. The incidence of osseous lesions was assessed and the findings were compared with those at arthroscopy. A total of 28 osseous lesions were detected by MRI in 15 knees, but none of these were detected by radiographs or arthroscopy. PMID- 8213121 TI - Cruciate ligament prosthesis vs. augmentation. A randomized, prospective 5-year follow-up of 41 cases. AB - In a prospective study, 18 patients were randomized to a prosthesis and 23 patients to the Kennedy Ligament Augmentation Device (LAD) because of functional instability due to old anterior cruciate ligament injuries. The operations were performed with use of a modified over-the-top technique. At the last follow-up (5 years), postoperative improvements in scores were maintained for both groups, but LAD-reconstructed patients had better Lysholm and activity scores than the Goretex group. The achieved postoperative improvement in anterior stability (KT 1000) did not deteriorate for either of the groups during the 5-year follow-up. The Goretex patients had more effusion and pain and more secondary operations. PMID- 8213123 TI - Knee articular cartilage injury in leg lengthening. Histological studies in rabbits. AB - The effect of lengthening the tibia, by callotasis on the articular cartilage in the knee, was investigated histologically in 18 rabbits. The distraction rate was 1 mm per day. On the right tibia, the distraction frequency was in 2 steps (0.5mm/12 hours), while on the left it was in 120 steps (0.0083 mm/12 minutes). The 18 animals were divided into 3 subgroups based on length gain. Cartilage and subchondral bone samples were examined by light and fluorescent microscopy. The incidence of cartilage degeneration on the 2-step side was 2/5, 5/6, and 6/7 at 10, 20, and 30 percent length increases. On the 120-step side it was 0/5, 1/6, and 1/7 at the same length increases. The intensity of tetracycline fluorescence of the subchondral plate on the 2-step side was higher than that on the 120-step side, showing 1.7, 2.0, and 2.3-fold increases at 10, 20, and 30 percent length increases. Our study suggests that increasing the frequency of distraction in callotasis can help to prevent damage to articular cartilage in adjacent joints. PMID- 8213124 TI - Chondrocyte behavior in fibrin glue in vitro. AB - To test fibrin glue as a vehicle in chondrocyte transplantation, chondrocytes, isolated from articular cartilage of young rabbits, were mixed with Tissucol, a highly concentrated fibrin glue, and cultured for 7 days. Histology, autoradiography (35-S) and electron microscopy were used to study chondrocyte behavior and phenotypic expression. Chondrocytes multiplied, retained their morphology, and produced matrix in fibrin glue as long as the cells were surrounded by the glue. Glue disintegration started after 3 days and was accelerated by higher cell concentrations. PMID- 8213125 TI - Arthroscopic repair of the bucket-handle meniscus. 10 failures in 27 stable knees followed for 3 years. AB - In a total of 535 meniscal lesions diagnosed by arthroscopy, 54 patients had their meniscus sutured arthroscopically. 25 cases were excluded from the study due to concomitant ligamentous injury, while 2 were lost to follow-up, leaving 27 cases of arthroscopic repair of isolated bucket-handle meniscal tears for review. 8 cases had the repaired meniscus partially resected later due to recurring symptoms. The remaining 19 cases were scored for knee function and activity after a median observation time of 36 (18-52) months. 15 of 19 patients with a supposedly healed meniscus had normal knee function, i.e., unchanged compared to preinjury levels, but a slight drop in median activity score. With 8 re-ruptures and 2 patients who stated result as poor, the 10/27 failure rate was rather high. Our results are not as good as most reported previously. PMID- 8213126 TI - Effects of distraction and compression on proliferation of growth plate chondrocytes. A study in rabbits. AB - An external fixation device was applied across the distal femoral physis in 30 rabbits, and distraction or compression was performed for 3-21 days; either no operation or a sham-operation was performed on the contralateral side. Proliferating cells were labeled with 5-bromo-2'-deoxyuridine, a thymidine analogue, and subsequently localized in decalcified histologic sections using a specific monoclonal antibody. The height of the proliferative and hypertrophic zones was increased after distraction; additionally, fracture-separation through the hypertrophic zone or at the junction of the physis and metaphysis was seen in 13 of the 15 specimens. Labeled cells were encountered only in the proliferative zone in all specimens except after early distraction, where labeled chondrocytes were seen close to the separation gap in the hypertrophic zone, too. Distraction had no effect on the number of labeled cells. A reduction in the height of the proliferative and hypertrophic zones occurred after compression, and the number of proliferating chondrocytes decreased. PMID- 8213127 TI - Screening for idiopathic scoliosis. Comparison of 90 cases shows less surgery by early diagnosis. AB - We assessed the final outcome of curve progression in 90 consecutive school children with idiopathic scoliosis. 46 children treated 1971-76 were compared with 44 treated 1978-81, after the introduction of school screening in 1977. There was a decrease in demand for surgery from 45 percent before screening to 10 percent in the screening group. When differences in subsequent brace types were accounted for, the outcome remained better in cases detected during the screening period. The most probable explanation is the earlier onset of bracing in the screened group. PMID- 8213128 TI - Injuries in competitive junior ice-hockey. 1437 players followed for one season. AB - During one season we followed 1437 ice-hockey players, 9-18 years of age, participating in a junior league. We found 128 injuries (9 percent) that caused the player to miss at least one training session or game. One third of the injuries were a result of foul play. The most common types of injury were contusions, sprains, and lacerations. However, fissures and fractures were surprisingly frequent, reflecting foul play with the stick and improper use of the protective equipment. Thanks to the mandatory use of a completely-covering face protector, there were few maxillofacial injuries. The highest yearly incidence of injuries was found in the older players. Prevention of ice hockey injuries is multifactorial, including stricter rule enforcement, improved protective equipment, and better understanding of the forces involved. PMID- 8213129 TI - Ulnar wrist pain after Colles' fracture. 109 fractures followed for 4 years. AB - 109 patients with unilateral Colles' fracture, treated with closed reduction and cast immobilization, were re-examined after 4 (1-9) years. At follow-up, 40 patients had persistent ulnar wrist pain. The most important factor for predicting ulnar pain was final dorsal angulation of the radius. Initial and final radial shortening, fracture of the distal radioulnar joint, ulnar styloid fracture, or instability of the distal ulna were not correlated to ulnar wrist pain. We suggest that ulnar wrist pain following Colles' fracture is caused by incongruity of the distal radioulnar joint. PMID- 8213130 TI - Posttraumatic carpal instability. A 9-year follow-up of 18 patients. AB - We present a 9 (1-20) year follow-up of 18 cases of carpal instability. Excluding 4 arthrodeses, 12 cases were satisfactory in terms of pain and grip strength in spite of persisting radiographic instability in 9. PMID- 8213131 TI - Fractures of the hook of the hamate in athletes. 8 cases followed for 6 years. AB - In 8 cases the fractured hook of the hamate was excised. Associated conditions included rupture of flexor tendons in 3 cases and ulnar nerve paresthesia in 2 cases. In 5 cases tomography was required to establish the diagnosis. Postoperative results with 6 years follow-up were good. PMID- 8213132 TI - Silicone replacement for non-union of the scaphoid. 7 cases followed for 9 (5-18) years. AB - In the years 1971-1983, 7 patients underwent excision of the scaphoid with replacement by a silicone rubber implant because of painful nonunion of a scaphoid fracture. The patients were reviewed 9 (4.5-18) years postoperatively. All patients returned to work, 2 patients being completely pain-free, 4 having only occasional pain on heavy activity, and 1 having pain on normal activity. The range of motion, power and pinch grip were near-normal in all. Radiographic examination showed progressive dorsal intercalated segment instability with carpal collapse and arthrosis. There was no evidence of fragmentation of, or reaction to the prosthesis. 1 prosthesis was dislocated, and no patient required a revision operation. PMID- 8213133 TI - Carpal-tunnel syndrome in hemodialysis. Syndrome diagnosed in 8 of 60 patients. AB - Clinical and electrophysiological examination for carpal-tunnel syndrome was performed in 60 consecutive hemodialysis patients. The syndrome was diagnosed in 8 patients, 6 of whom had had hemodialysis for more than 10 years. Cystic radiolucency in the carpal bone, possibly a sign of amyloid deposition, was observed more frequently in carpal-tunnel patients and amyloid-induced tenosynovitis in the carpal-tunnel had formed in 4 cases. PMID- 8213134 TI - Acute nerve compression at low pressures has a conditioning lesion effect on rat sciatic nerves. AB - Effects of acute compression for 2 hours around the sciatic nerve trunk at 30 or 80 mmHg on the regeneration potential in rat sciatic nerves were studied. Sham compression or mobilization was performed contralaterally. A week later a crush injury was inflicted proximal to the compressed segment. After another 3 or 6 days the length of axonal outgrowth was measured, using the pinch test technique. We found that compression at either level caused an increased length of axonal outgrowth compared to the mobilized or sham-compressed nerves. The results show that an acute compression at low pressures does have a conditioning lesion effect on peripheral nerves. PMID- 8213135 TI - The ankle fracture as an index of future fracture risk. A 25-40 year follow-up of 1063 cases. AB - In 1992 a retrospective case control study was performed, based on all patients with ankle fractures (n 1063) treated at the Department of Orthopedics in Malmo, Sweden, between 1950-1951 and 1961-1965. As all radiographic examinations have been saved in Malmo, we were able to study all subsequent fractures that this group had sustained. 260 patients from 1961-1965 who were still living in Malmo today were also compared with an age- and gender-matched control group regarding the location and type of subsequent fractures. The group with former ankle fractures continued to have a two-fold increase incidence of all sorts of fractures. The same result was found when looking at the upper and lower extremities separately. However, the risk of sustaining new fractures in the once fractured extremity was not increased compared to the uninjured side. PMID- 8213136 TI - The subacromial bursa and the impingement syndrome. A clinical and histological study of 30 cases. AB - Biopsies from the subacromial bursa were obtained from 30 patients with an impingement syndrome and from an autopsy series of 13 "normal" shoulders. Bursal fibrosis seemed to be a characteristic of the patient group; inflammatory cells, found in 7/30 specimens from the patients, were not found in the autopsy series. The microscopic findings could not be predicted from peroperative observations. There was an association between a poor outcome of surgery and absence of bursal fibrosis. PMID- 8213137 TI - Calcified thoracic disc herniation with paraparesis. A case report. AB - We present a case with partially calcified thoracic discs, one of which extruded into the spinal canal with paraparesis. The paste-like consistency complicated excision. PMID- 8213138 TI - A case of massive osteolysis after knee prosthesis polyethylene failure. AB - A case of massive osteolysis of the distal femur in response to particulate polyethylene from a broken uncemented tibial component is described. The osteolysis was so extensive that it made the revision arthroplasty extremely difficult. Early detection and early revision is recommended. PMID- 8213139 TI - Recovery from low back pain. 1-5 year follow-up of 287 injury-related cases. AB - This study investigated the factors affecting recovery from low back injury. The study population was designed to be representative of patients presenting with back pain following soft tissue injury. A minimum follow up rate of 90 percent was achieved with a length of elapsed time from the injury of up to five years. Three established methods of assessment of disability and functional capacity (The Oswestry disability scale, The Waddell disability scale and The Waddell physical impairment rating) were compared to each other and a new scale (The Low Back Outcome Scale) for the measurement of a patient's performance in employment, social activities and activities of daily living. The relationships of these scales to employment, psychological disturbance and other factors were defined. The Outcome Score designed for use in this study provided a comprehensive and discriminating assessment of patient function. Compensation (particularly lump sum claims), psychological disturbance at review, time off work, and age at injury were important factors in recovery; the diagnosis, type and severity of injury, migrant status and neurological deficits were not. Eight psychometric instruments were examined, and the combination of The Zung Depression Scale and The Modified Somatic Perception Questionnaire was found to be the most accurate in determining the presence of psychological disturbance in patients with low back pain. PMID- 8213140 TI - The classification and treatment of Meniere's disease. AB - The classification and treatment of Meniere's disease are especially difficult because the natural history of Meniere's disease is so variable, and not possible to relate to the cochlear and vestibular pathology present, which is constantly changing and cannot be known during life. In the many new papers written each year on Meniere's disease and the hundreds of older papers already in the medical literature, there is no good agreement about the definition of Meniere's disease, the pathology and natural history, and the real benefit of the medical and surgical treatments given. Only recently, with transtympanic electrocochleography and three-dimensional CT scans of the external aperture of the vestibular aqueduct, have we significant information during life about the pathology present, from which to predict the likely natural history and the chances for successful treatment. This paper will define Meniere's disease, will separate its pathology and natural history in five stages, and suggest reasonable methods of treatment for the stages for which treatment is possible. PMID- 8213141 TI - Management of labyrinthine fistulas in cholesteatoma. AB - Surgical management of labyrinthine fistulas caused by cholesteatoma remains controversial. In 213 patients with middle ear surgery for cholesteatoma, 18 patients (18 ears-8.5%) presented a labyrinthine fistula. These cases are reviewed in the present paper. Symptoms, audiometry, pre-operative imaging, surgical procedure and results are discussed. In all cases total removal of the pathology was pursued with preservation of cochlear function. A two-stage closed technique was used. During the first stage reconstruction with tympano-ossicular allografts, according to the technique of J. Marquet, was performed. A second look followed one year later. Three ears were deaf pre-operatively. Improvement of bone conduction was observed in more than 50% and hearing preservation in all other cases but one. In one ear total deafness occurred from extensive intralabyrinthine invasion by cholesteatoma, demanding a labyrinthectomy. The hearing was preserved in four cases in which an amputation of a large part of the membranous labyrinth could be observed. Since neither pre-operative clinical examination nor imaging can be relied on to reveal a fistula, the surgeon needs to be prepared for unexpected fistulas. PMID- 8213142 TI - [Neurinoma of the VIIIth cranial nerve with negative electrophysiological findings]. AB - Electrophysiological features in acoustic neurinoma are reviewed. A case of an acoustic neurinoma with a normal BERA is reported. The authors conclude that no isolated electrophysiological sign is able to disclose a retrocochlear hearing loss. They insist on the necessity to interpret an unilateral hearing loss on basis of an integration of a complete clinical, paraclinical and electrophysiological testing. PMID- 8213143 TI - Stereolithographic modelling for reconstructive head surgery. AB - Until now, bounds of model creation of medical objects had to be set because of the limited capabilities of available manufacturing equipment. Recently, stereolithography was developed as an alternative to current milling operations. In this process the surface of a photohardening liquid plastic compound is traced by a laser beam and hardened in layers. The models thus produced are extremely accurate and retain excellent detail. Specific implants can be designed and prepared as is illustrated in a case report. If tissue-compatible plastics are used, custom-made implants could soon be manufactured directly with the technique described. PMID- 8213144 TI - Reconstruction of defects in the anterior skull base with calcium phosphate ceramics. AB - Hydroxylapatite and tricalcium phosphate are bioactive ceramic materials resembling the mineral matrix of bone. Implants have been used for the reconstruction of the posterior auditory canal wall and the ossicular chain. In this report the application of macroporous biphasic calcium phosphate implants for the reconstruction of defects in the anterior skull base is described. A mixture of granules of tricalcium phosphate and hydroxylapatite (Triosite, Xomed Zimmer Inc) and two-component fibrin adhesive (Tissucol, Immuno AG Wien) is used. The technique is presented in detail and preliminary results are discussed. PMID- 8213145 TI - Clinical aspects of vocal cord nodules. AB - A clinical study of 251 patients with vocal nodules who underwent endolaryngeal microsurgery and speech therapy, was carried out. The postoperative results were evaluated. All patients were examined by videostroboscopy. An original acoustic method was applied for the estimation of the voice before and after therapy. Different patterns for vocal nodules were discussed. PMID- 8213147 TI - Accessory nerve electroneurography by magnetic stimulation in normal subjects. AB - An electroneurographic study was made of the accessory nerve in 15 healthy subjects by conventional peripheral electrical stimulation and transcranial magnetic stimulation at three different levels: cortical contralateral (frontoparietal), homolateral occipital and at the base of the skull. The motor evoked potential (MEP) obtained by magnetic stimulation at the skull base exhibited greater latency and amplitude than that recorded by conventional peripheral electrical stimulation. The MEP obtained by stimulating at occipital level again exhibited a greater latency than that corresponding to skull base stimulation, but the amplitude was smaller. Finally, the MEP resulting from cortical stimulation failed to appear uniformly in all of the individuals studied. Its amplitude was smaller than in the previous cases, with a mean latency of 11.76 ms and a central conduction time of 7.5 ms. The magnetic stimulation technique allowed the efficient, painless, non-invasive and easily reproducible study of the motor pathway of the spinal nerve over its entire trajectory (motor cortex-motor neuron-muscle). PMID- 8213146 TI - [3 cases of pediatric subglottic stenosis: use of high-frequency jet ventilation]. AB - High frequency jet ventilation permits an effective diagnostic and surgical approach with unobstructed view of a compromised airway allowing treatment ranging from imminent surgical intervention to an attitude of observation. PMID- 8213148 TI - The changing aspect of thyroid surgery: a review of 130 consecutive cases. AB - A retrospective analysis was performed on 130 thyroid gland operations from January 1986 to September 1992. In 69% a lobectomy and in 28% a subtotal thyroidectomy was performed for benign thyroid disorders. A total thyroidectomy for malignancy was required in only 3%. Recurrences, operated earlier elsewhere accounted for 6% of the cases. A dramatic fall in diagnostic lobectomies is seen through the years since the use of Fine Needle Aspiration (FNA) as a decisive tool in surgical strategy. The total load of thyroid surgery remains the same, but it has become more therapeutic: hyperthyroidism and relief of tracheo oesophageal compression by large goiters have become the major indications for surgery. These procedures are more demanding on the surgeon, but early surgery and standard technique can keep complications to a minimum. PMID- 8213149 TI - [Necrotizing sialometaplasia: an ignored disease]. AB - Necrotizing sialometaplasia is an ignored pathology. Differential diagnosis has to be made with a neoplasm. The presented case is characterized by an important bone defect, which, to our knowledge, has never been reported. PMID- 8213150 TI - Botulinum A toxin injection in patients with facial nerve palsy. AB - The preliminary experience of the authors with Botulinum toxin injections as a therapeutic tool for the ocular problems following facial nerve palsy is reported. Patients attained with facial nerve palsy who might benefit from Botulinum toxin were divided into three groups according to their eye problem: incomplete eyelid closure, postparalytic secondary facial spasm with synkinesis and contracture of the internal rectus muscle in the case of association with an abducens nerve palsy. PMID- 8213151 TI - [Diagnostic and therapeutic management of the patient with headache]. AB - The different diagnostical and therapeutical approaches of cephalalgia are described. The importance of a pluridisciplinary management is stressed. PMID- 8213152 TI - [Team work in the treatment of patients with congenital craniofacial malformations]. AB - The longlasting multidisciplinary approach of patients born with craniofacial deformities is reviewed. A schedule of treatment depending on the severity of the cleft is proposed. PMID- 8213153 TI - The Human Genome Project and clinical medicine: adenomatous polyposis coli and the Marfan syndrome as examples. PMID- 8213154 TI - Clinical manifestation of mitochondrial diseases in children. AB - Fourteen patients (10 boys, 4 girls) aged from 4 months to 14 years old were diagnosed with mitochondrial disease based on the clinical manifestations together with abnormal muscle mitochondrial morphologies. Their clinical diagnoses included Leigh syndrome, three; Menkes' syndrome, three; Kearns-Sayre syndrome, two; myoclonic epilepsy with ragged fibres, one; and infant-onset progressive myoclonic epilepsy, one; fatal infantile mitochondrial myopathy, one; fatty acid oxidation defect, two; and myopathy with cardiopathy, one. Organs involved other than muscles included central nervous system, ten; heart, six; eye, two; liver, two; and kidney, two. Clinical manifestations varied to include hypotonia, seizures, myoclonus, mental retardation, nystagmus, ataxia, ptosis, ophthalmoplegia, retinal degeneration, muscle atrophy, spasticity etc. Nine had an abnormal rise in lactate after glucose loading. Ragged-red fibres were found in four patients. Abnormal mitochondrial morphology included abnormal accumulation, abnormal cristae pattern of tubular, concentric, or parallel form, some contained osmiophilic inclusion bodies. One patient of Leigh syndrome had had brain necropsy which showed intramyelin splitting of myelinated axons. PMID- 8213155 TI - Candida tropicalis fungemia in children with leukemia and lymphoma. AB - Five episodes of fungemias are described; all had occurred in children with leukemia or lymphoma between January 1, 1978 and December 31, 1990. These fungemias comprised 3.4% of the total septicemias encountered during that period. Three episodes occurred during the induction phase and two during relapse. All patients had fever of varying degree and duration. In addition to steroids, all were receiving combination antibiotics before the fungemia had occurred. All patients had severe neutropenia lasting more than one week. Bacteremia preceded fungemia in four patients. Two episodes were diagnosed antemortem. The same species were isolated from other sites in three cases. Fever, chills and gastrointestinal symptoms were the most common clinical features; other symptoms included cough, dyspnea, oliguria and azotemia. One patient experienced skin lesion, dysphagia, hoarseness and hemiparesis. Only one patient survived. The prognosis from fungemia in leukemia and lymphoma patients is very poor. Empiric antifungal therapy is indicated in neutropenic patients who have recurrent or persistent fever despite one week of broad spectrum antibiotics. Early diagnosis and treatment will aid in improving the overall poor outcome of this disease. PMID- 8213156 TI - Total parenteral nutrition-associated cholestasis in infants: clinical and liver histologic studies. AB - To evaluate total parenteral nutrition-associated cholestasis (TPN-C) in infants, a retrospective clinicopathologic study was conducted of 15 infants who had received TPN. The mean gestational age and birth weight were 32.1 weeks (26-40 weeks) and 1807 g (840-5840 g) respectively. Two-thirds of the patients were kept on TPN for more than 60 days. The onset of rising direct bilirubin ranged 2-9 weeks (mean 4.5 +/- 2.4) after TPN therapy. Preterm babies less than 32 weeks of age had an earlier rise of direct bilirubin and AST. Bile sludge of the gallbladder was observed in only one case, and none had gallstone. The main histologic findings of liver biopsy or autopsy were cholestasis (intracellular and canalicular), periportal inflammation, fibrosis and bile ductular proliferation. Sixty percent of these survived, the remaining 40% died of complications unrelated to TPN-C. The liver function profile became normalized within a mean of 14.0 +/- 9.4 (8-34) weeks after discontinuation of TPN in the survival cases. It was concluded that infant TPN-associated cholestasis was mostly reversible, but that the younger preterm babies were susceptible to a prolonged TPN course with more marked clinical and pathological changes. PMID- 8213157 TI - The 30-minute (1-24)ACTH test for evaluation of adrenocortical function in childhood. AB - Twenty-eight children with normal adrenocortical function and two patients with adrenocortical insufficiency were enrolled in the present study. The ACTH test was performed in these 30 children, and the insulin hypoglycemia test was also performed for the same group, except for one with Addison's disease. Serum cortisol response after intravenous administration of (1-24)ACTH was below normal range in two patients with adrenocortical insufficiency. Neither significant correlation nor statistically significant difference was found between the serum cortisol level 30 minutes after (1-24)ACTH and the peak cortisol value during the insulin hypoglycemia test. None of these children had any adverse reaction to ACTH test. This study suggests that the 30-minute (1-24)ACTH test is a simple, safe and valuable screening procedure for evaluation of adrenocortical function in children. PMID- 8213158 TI - [Correlation between development indices and later intelligence quotients--the follow-up study of chlorinated biphenyls affected children]. AB - All intelligence tests are for children old than two and a half years; we still do not have an intelligence assessment tool for children younger than this age. If we knew the relationship between the intelligence quotient and developmental indices as measured by the Bayley Scale of Infant Development (BSID), it would allow us to assess the mental development of young children earlier and to start adequate management sooner. The present study was designed to meet this need. We collected our data from a six-year follow-up study of Yu-Cheng (oil disease) children born to mothers who had a history of ingesting rice cooking oil contaminated with polychlorinated biphenyls (PCBs) in 1978-1979 and their matched controls. We analyzed the correlations between the developmental indices of the BSID assessed on 44 pairs of Yu-Cheng children and their controls in 1985 and the Stanford-Binet Intelligence Quotients (S-B IQ) assessed on the same group of children in 1987 and 1988. For the matched controls, we found practically no significant correlation between the BSID developmental indices and the S-B IQ (r = .04-.20, p = .23-.82). In the Yu-Cheng children, that is at-risk group, there was a significant correlation between the Mental Developmental Index (MDI) of BSID and the S-B IQ (r = .33-.43, p = .01-.05) and between the Psychomotor Developmental Index (PDI) of BSID and the S-B IQ (r = .31-.47, p = .00-.07). We conclude that the development indices of BSID has a better predictive power on the intelligence among the at-risk group such as Yu-Cheng children. PMID- 8213159 TI - Investigation and elimination of epidemic methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit. AB - A recent outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infection in neonatal intensive care unit (NICU) in a teaching hospital was investigated. A total of 25 MRSA isolates, 16 from the patients and nine from the staffs (carriers), was collected for the study. The possible relationship among the isolates was investigated by using antibiograms and restriction enzyme analysis of plasmid DNA. Control strategy of the MRSA nosocomial infection was proposed after the study of antibiograms and plasmid profile. There were four plasmid patterns (I-IV), each containing 7, 8, 2, and 8 isolates. Six of the 16 isolates from the patients had identical plasmid patterns as the carriers (I and II). Person to person transfer via hand contact by medical personnel was found to be the most frequent mode of transmission identified in the outbreak of MRSA nosocomial infection in the NICU. Our strategy for control of the outbreak and elimination of the MRSA from all patients and carriers was successful after intensive surveillance and control measures. These included (a) strict isolation and cohorting; (b) hand washing between patient contacts to prevent transmission; (c) treatment of the carrier state in health care workers and patients with safe and effective topical agents such as mupirocin. PMID- 8213160 TI - Delayed-onset intraventricular hemorrhage in a full-term neonate: report of one case. AB - Intraventricular hemorrhage (IVH) in the full-term neonates is not as common as in the premature neonates. We describes a full-term neonate who presented with delayed onset of intraventricular hemorrhage and fever. Her perinatal and delivery course were uncomplicated. Clinically, omphalitis was found on admission. However, no definite etiology of IVH was discovered. Follow-up brain sonography at the age of seven months revealed complete resolution of IVH. The prognosis of the patient was good on follow-up, which was comparable with other reports. PMID- 8213161 TI - Leigh disease (subacute necrotizing encephalomyelopathy): report of one case. AB - A case is reported of a 16-month-old girl who presented with generalized hypotonia, ptosis and persistent low grade fever after a previous pneumonia. Brain CT and MRI showed symmetric necrotizing lesions in the basal ganglia, substantia nigra and periaqueduct area. Lactate and pyruvate levels were elevated in both the blood and cerebrospinal fluid. Biopsy of the rectus femoris muscle for electron microscopic examination revealed some distortion of the mitochondrial cristae. Biochemical study showed normal respiratory chain enzymes. Leigh disease was considered from the neuroradiological findings and morphological investigations. PMID- 8213162 TI - Intramyelin splitting in the spongiform lesions of Leigh syndrome. AB - A 5-month-old male infant, diagnosed as Leigh syndrome, presented with developmental delay, episodic apnea, metabolic acidosis, and myoclonic seizures. The magnetic resonance image of brain showed multiple symmetric low signals over the putamen in the T1-weighted axial view and linear high signal over the brainstem in the T2-weighted sagittal view. On electron microscopy, subsarcolemmal aggregation of abnormal mitochondria in muscle cells were found via biopsy. Small samples of myocardium, liver and brainstem, obtained via necropsy, were subjected to pathological examinations. On light microscopy, vacuoles were found in the myocardium and hepatocytes, while spongiform lesions in the neuropils, round cell infiltration, and vascular proliferation were observed in the brainstem. On electron microscopy, intramyelin splittings were observed in the spongiform lesions. We believe that intramyelin splitting must play an important role in the pathogenesis of spongiform lesions in Leigh syndrome. PMID- 8213163 TI - Cystic fibrosis in two Chinese infants in Taiwan. AB - Cystic fibrosis was diagnosed in two female infants, respectively nine months old (Case 1) and six months old (Case 2). Clinical presentation of these two infants showed frequent episodes of pneumonia, dehydration and poor weight gain, despite fair intake of food since birth. Hyponatremic, hypochloremic metabolic alkalosis had been found during their previous hospitalizations. In Case 1, stool fat was positive with negative trypsin test. Both cases had abnormal findings on chest X ray films, but the pancreas showed no remarkable cystic changes from sonography. Plastic-bag method of sweat test showed Na/Cl: 155/185 nmol/L in Case 1, Na/Cl: 127/135 nmol/L in Case 2. A family history was suggested, since each one had an elder brother who had died in early infancy with similar clinical presentations. Both patients were put on special diet therapy as well as chest physical therapy. Case 1 died suddenly at 16 months of age. Autopsy revealed mucusplugged dilated ducts with atrophy of the exocrine portion of the pancreas. DNA analysis in Case 2 showed abnormal mutation point at 1898+5 G-->T on chromosome 7. PMID- 8213164 TI - [Antithrombotic and antiplatelet effects of rosmarinic acid, a water-soluble component isolated from radix Salviae miltiorrhizae (danshen)]. AB - Wistar rats of both sex were used. Ros A was intravenously injected 5-10 min before blood collection or the ligation of vena cava. 1. Stasis-induced venous thrombosis: A tight ligature was applied to inferior vena cava below the left renal vein in anesthetized rats. The abdominal walls were closed and then reopened two hours later. The vena cava was clamped 2 cm below the ligature. This segment was cut to remove the thrombus. The dry weight of the thrombus was determined. 2. Platelet aggregation: Using Born's method the platelet aggregation induced by collagen or ADP was studied. 3. Blood coagulation times: Blood recalcium time (RT), kaolin partial thromboplastin time (KPTT) and prothrombin time (PT) were estimated. 4. Plasma fibrinolytic activity was observed by the determination of euglobulinolytic time (ELT). Plasma fibrinogen content was estimated based on the biuret reaction. The venous thrombosis was inhibited by 41.9% and 54.8% (P < 0.05) when Ros A was injected at the dosages of 50 and 100 mg/kg. The blood platelet aggregation elicited by collagen was suppressed by 30.4% (P < 0.05) and 46.4% (P < 0.01) after the injection of Ros A at doses of 100 and 150 mg/kg respectively. The ELT was shortened after the injection of Ros A (100 and 150 mg/kg) as compared with the control value (P < 0.05), while the plasma fibrinogen content remained unchanged. The results that Ros A showed mild antithrombotic effect. The mechanism of this effect might be related to its inhibition of platelet aggregation and promotion of fibrinolytic activity. PMID- 8213165 TI - [Effects of atropine on contraction of rabbit aortic smooth muscle and cell proliferation]. AB - The calcium antagonistic actions of atropine (Atr) and verapamil (Ver) were studied on the contraction of rabbit thoracic aorta strips induced by CaCl2 and KCl. Both Atr and Ver were found to depress the contraction as demonstrated by the shift-to-right of the dose-effect relationship curves and the decrease of maximal responses, with the value of pD'2 being 4.4 and 5.8 respectively. The intracellular Ca(2+)-dependent component of NE-induced aortic strip contraction was also inhibited by the 2 drugs, but the extracellular Ca(2+)-dependent component was barely or not inhibited by Atr before its concentration was raised to 100 mumol/L. These results indicate that the depressive effect of Atr on aortic contraction is mainly exerted by acting on the PDC (potential-dependent channel). The action of Atr on proliferation of cells was also studied in rabbit aortic smooth muscle cell (ASMC) culture. The growth was inhibited by Atr when Ca2+ was present in the medium. When Ca2+ was absent, however, the growth was stimulated by Atr 20.6-185.2 mumol/L, but inhibited by Atr 555.7-1666.7 mumol/L, suggesting that Ca2+ is somehow involved in the action of Atr on ASMC growth. PMID- 8213166 TI - [Pharmacokinetics of epostane in rats]. AB - After rats were given (ig) epostane 50, 100 and 200 mg.kg-1, plasma concentrations of epostane were determined by HPLC. According to concentration versus time data, the pharmacokinetic model of epostane in all rats followed a pattern of one-compartment model. The pharmacokinetic parameters of the three doses were found to be as follows: Ka were 0.578 h-1, 0.553 h-1 and 0.439 h-1; K were 0.308 h-1, 0.282 h-1 and 0.224 h-1; T1/2 were 2.27 h, 2.54 h, 3.12 h and AUC were 786.89 micrograms.h.ml-1, 1644.43 micrograms.h.ml-1, and 3335.35 micrograms.h-1.ml-1 respectively. The tissue distribution of epostane in rats were as follows: highest in adrenal, liver, gastrointestinal tract, uterus and ovary; next in kidney, heart, brain, lung and spleen. The peak concentration times were about 3 h and comparable to plasma peak time. Plasma protein binding of epostane was determined by equilibrant dialysis of the plasma of rats given the drug and found that the degree of binding was not correlated with drug dosage under our experimental conditions. Little epostane was found in the bile, urine and feces. It appears that epostane might have undergone extensive biotransformation in the rat body. PMID- 8213167 TI - [Effects of 6-(alpha alpha-diphenylacetylpiperazinyl) phenyl-5-methyl-4,5-dihydro 3 (2H)-pyridazinone on rabbit platelet aggregation and TXB2, cAMP production]. AB - 6-(alpha alpha-diphenylacetylpiperazinyl) phenyl-5-methyl-4,5-dihydro-3 (2H) pyridazinone (DMDP) is a new synthetic pyridazinone derivative. This compound was shown to inhibit AA, ADP and PAF-induced rabbit platelet aggregation, and its IC50s were found to be 1.12 +/- 0.1, 4.19 +/- 0.5 and 2.97 +/- 0.1 mumol/L, respectively. At the concentration range of 1-500 mumol/L, the compound was found to depress TXB2 content and to increase cAMP levels in washed rabbit platelets in a dose-dependent manner. These might be the mechanisms of the compound on the inhibition of rabbit platelets. PMID- 8213168 TI - [Antitumor effect of the immunoconjugate composed of antibiotic C1027 and Fab fragment from a monoclonal antibody directed against human hepatoma]. AB - Antibiotic C1027, a macromolecular peptide with highly potent cytotoxicity to cultured cancer cells, was conjugated to monoclonal antibody 3A5 and its Fab fragment separately using SPDP as the linker agent. McAb 3A5, identified as IgG1, was directed against human hepatoma BEL-7402 cells. By ELISA, McAb 3A5 and the Fab fragment were strongly reactive with hepatoma cells and weakly reactive with KB cells. Determined by clonogenic assay against hepatoma BEL-7402 cells, the IC50 values for McAb-C1027, Fab-C1027 and C1027 were 4.2 x 10(-14), 8.6 x 10(-16) and 6.5 x 10(-16) mol.L-1, respectively. Fab-C1027 was 49-fold more potent than McAb-C1027 in cytotoxicity. Moreover, Fab-C1027 was 160-fold more potent in cytotoxicity to hepatoma cells than to KB cells, indicating selective cytotoxicity of Fab-C1027 conjugate to the target cells. Therapeutic effect of the conjugate was evaluated with hepatoma BEL-7402 xenograft in nude mice. After subcutaneous transplantation of the tumor, treatment started on day 3, iv, with equivalent dose of C1027, 0.1 mg.kg-1 x 6. Fab-C1027 and free C1027 inhibited tumor growth by 85% and 59%, respectively. Fab-C1027 conjugate showed more marked antitumor effect in vivo than free C1027. PMID- 8213169 TI - [Synthesis and bio-activity of coumarin derivatives and studies on its relationships between activity and lipophilicity]. AB - 4-Methyl-7-hydroxy-6 or 8-allylcoumarin, a new type of radioprotectors, has poor solubility in water and in oil, which influences markedly its absorption in body and effectiveness of peroral administration. For improving its solubility, 14 coumarin derivatives were synthesized on the basis of increasing its hydro- or lipophilicity, and studied preliminarily on their toxicities, radioprotective activities, and relations between their hydro- or lipophilicity and activities. It is found that both compounds (5a, 6a), can be dissolved in ethyl oleate and the latter in water partially as well, retain the radioprotective activities basically, and improve the survival of 65% (P < 0.01) of mice exposed to 9.0 Gy 60Co gamma-ray when administered before irradiation. In synthesis, von Pechmann reaction was improved; 6-allyl intermediate was synthesized by the method of blocking the 8-position by iodine, and the process was studied. Mannich base was synthesized under high pressure by using CH2Cl2 as C1 synthon. PMID- 8213170 TI - [Studies on the chemical constituents of Lonicera macranthoides Hand. -Mazz]. AB - Three bisdesmosidic triterpenoid saponins I-III, have been isolated from the flowers of Lonicera macranthoides Hand. -Mazz. By spectral (IR, MS, 1H-NMR and 13C-NMR) and chemical methods, I was proved to be identical with the known dipsacoside B, II and III were new compounds named macranthoidin A and macranthoidin B. Their structures were identified as follows: The prosapogenin of II, macranthoside A(IIb), was elucidated as 3-O-beta-D-glucopyranosyl-(1-3)-alpha L-rhamnopyranosyl-(1-2)-alpha-L- arabinopyranosyl 3 beta, 23-dihydroxyl-olean-12 en-28-olic acid, II was established as 3-O-beta-D-glucopyranosyl-(1-3)-alpha-L rhamnopyranosyl-(1-2)-alpha-L- arabinopyranosyl 3 beta,23-dihydroxyl-olean-12-en 28-O-beta-D-glucopyranosyl-(1-6)-beta-D- glucopyranoside. The prosapogenin of III, macranthoside B(IIIb), was elucidated as 3-O-beta-D-glucopyranosyl-(1-4) beta-D-glucopyranosyl-(1-3)-alpha-L- rhamnopyranosyl-(1-2)-alpha-L arabinopyranosyl 3 beta,23-dihydroxyl-olean-12-en-28-olic acid, III was established as 3-O-beta-D-glucopyranosyl-(1-4)-beta-D-glucopyranosyl-(1-3)-alpha L- rhamnopyranosyl-(1-2)-alpha-L-arabinopyranosyl 3 beta,23-dihydroxyl-olean-12 en-28-O-beta-D-glucopyranosyl-(1-6)-beta-D- glucopyranoside. IIb and IIIb have not been reported in the literature. PMID- 8213171 TI - [Studies on CD spectra of derivatives of shikonin and alkannin]. AB - The circular dichroism (CD) and electronic absorption spectra of seven derivatives of shikonin and alkannin isolated from the roots of Onosma confertum W.W. Smith (from Sichuan) and Arnebia euchroma (Royle) Johust (from Xinjiang) were described. Each pair of CD spectra obtained was exact mirror images and the UV spectra of these compounds were very similar. In comparison with the CD spectra of shikonin given in literature, the configuration of the pigments from Sichuan was assigned R and from Xinjiang were all S. PMID- 8213172 TI - [Highperformance liquid chromatographic assay for lomefloxacin in plasma and its pharmacokinetics in healthy volunteers]. AB - A sensitive and simplified high performance liquid chromatographic procedure has been developed for quantification of lomefloxacin in human plasma. The recovery of lomefloxacin was 95 to 102%. The relative standard deviation was 2.1 to 7.8%. The calibration curve was linear in the range from 0.125 micrograms/ml to 5.012 micrograms/ml with r = 0.9998. The detection limit of the method is 25 ng/ml. The plasma drug concentration-time course after medication conformed to a 1 compartment open model with a first order absorption. Mean t1/2 value was 5.5 h. PMID- 8213173 TI - [The physical properties, pharmacology and antifertility action of crystal trichosanthin protein liposome]. AB - The crystal trichosanthin protein liposome (TPL) was prepared by an emulsion forming method. The rate of entrapment was 33.0-44.8% and the rate of recovery was 95.15-99.58%. The determination of trichosanthin protein was accomplished by spectrophotometry at 650 nm, thus eliminating completely the interference of lipids. The distribution of particle size of TPL was mainly in the range of 1-2 microns (96.9%). TPL was sterilized by 60Co radiation at 4 degrees C for 90 min and was stable when stored at 4 degrees C, 25 degrees C and 37 degrees C. The seepage rate of trichosanthin from the liposome was 15.22% after storage for 38 days at room temperature. Experiments showed that TPL had a slight allergic reaction, but was safe by hemolysis and coagulation tests. When the mice were given TPL ip 8 micrograms per animal 6 days after pregnancy, the rate of termination of early pregnancy was 83.3%. It thus appears that TPL can terminate early pregnancy in mice distinctly. This indicates that TPL may be expected to be developed into a new type of anti-early pregnancy preparation. PMID- 8213174 TI - [Studies on preparation technology of microspheres of contraceptives]. AB - Contraceptive poly ethylglycol-lactide (PEGL), an artificial biodegradable polymer microsphere was prepared by a solvent evaporation process using levonorgestrel (LNG) and estradiol (E2) as model drugs and PEGL as the core material. The experimental conditions were optimized, the mean volume diameter obtained being 30 microns and rate of encapsulation 75-82%. In vitro, it was found that the drug release rate decreased with decreasing drug content in the microspheres. The microspheres of the contraceptive maintained anticonception duration in mice for over 6 months, indicating that the microspheres have remarkably long acting sustained release action. PMID- 8213175 TI - [The synthesis and bioactivities of cholinergic tropane alkaloids]. AB - Ten analogs of baogongteng A, the natural cholinergic tropane alkaloid isolated from Erycibe obtusifolia Benth, were designed and synthesized. The tropane skeleton was kept unchanged, while the substituting groups on N and C3 were modified. In myotic experiments in rabbits 3-paramethyl benzoyloxy-6-acetoxy nortropane(4), 3-propionyloxy-6-acetoxy nortropane(5), and 3-isobutyryloxy-6 acetoxy nortropane(6) showed cholinergic activities. PMID- 8213176 TI - [A chiral capillary gas chromatographic method for direct determination of enantiomers of mephenytoin in human urine]. AB - A gas chromatographic method equipped with nitrogen-phosphorus detector was developed for the determination of the S- and R-enantiomers of the anticonvulsant, mephenytoin (MP) in human urine. Dichloromethane (4 ml) was added to 1 ml urine, the mixture was shaken and centrifuged. The organic phase was transferred to another tube and blown to dryness under nitrogen on water bath (37 degrees C). The residue was dissolved in 10 microliters ethylacetate and 1-2 microliters was injected into the GC. Our results showed that direct enantiomeric separation of mephenytoin was obtained by using a chiral capillary column, the retention times for S- and R-mephenytoin were 25.5 and 26.2 min respectively, with a detection limit less than 50 ng/ml of mephenytoin. Similar linear and reproducible standard curves were obtained over the concentration range of 53.2 to 2128.0 ng/ml (for S-MP, r = 0.9914 +/- 0.0070, n = 6; and for R-MP, r = 0.9939 +/- 0.0070, n = 6), and the mean recoveries of S- and R-MP were 95.4% and 95.8% respectively. The within-day relative standard deviations were less than 8.8% for both S- and R-MP, and that of between-days were less than 14.3%. There was a good reproducibility of the urine S/R mephenytoin determined in China and in Sweden by using similar method in 107 Chinese volunteers after a single oral dose of 100 mg racemic mephenytoin (r = 0.9091, P < 0.001). PMID- 8213177 TI - [Polarographic determination of carbamazepine in the presence of sodium lauryl sulfate]. AB - The electrochemical characteristics of carbamazepine (CBZ) have been studied. In a solution containing 0.40 mol.L-1 NaOH, 0.15 mol.L-1 KNO3 and 0.0020% sodium lauryl sulfate (SLS) CBZ gives a sensitive polarographic wave which can be used to determine trace amounts of the drug, the detection limit being 1.0 x 10(-6) mol.L-1. The cyclic voltammetric data show that SLS promotes adsorption of CBZ at the mercury electrode. PMID- 8213178 TI - [Study on the method for determination of analgin using flow injection spectrophotometry]. AB - A new flow injection spectrophotometric method for the determination of analgin has been developed. The main factors which affect the determination were investigated. The absorption maximum is 650 nm. Under optimum conditions the calibration graph is linear in the range of 0.2-3 mg/ml, the average recovery is 99.8% with a relative standard deviation of 0.5%. The proposed system permits the analysis of about 240 samples per hour and has the advantages of analytical efficiency, sensitivity and accuracy for the determination of analgin. PMID- 8213179 TI - Muscle fibre types and enzyme activities after training with local leg ischaemia in man. AB - Eight healthy men performed supine one-legged training on a bicycle ergometer 45 min per leg four times per week for 4 week. The ergometer and lower body were inside a pressure chamber, the opening of which was sealed at the level of the crotch. One leg trained with impeded leg blood flow (I-leg), induced by an increased (50 mmHg) chamber pressure, at the highest tolerable intensity. The contralateral leg trained at the same power under normal pressure (N-leg). Before and after training biopsies were taken from the vastus lateralis of both legs and maximal one-legged exercise tests were executed with both legs. Biopsies were repeated when the subjects had been back to their habitual physical activity for 3 months. Training increased exercise time to exhaustion, but more in the I-leg than in the N-leg. After training, the I-leg had higher activity of citrate synthase (CS), a marker of oxidative capacity, and lower activity of the M subunit of lactate dehydrogenase isoenzymes. It also had a higher percentage of type-I fibres and a lower percentage of IIB fibres, larger areas of all fibre types and a greater number of capillaries per fibre. It is concluded that ischaemic training changes the muscle metabolic profile in a direction facilitating aerobic metabolism. An altered fibre-type composition may contribute, but is not enough prerequisite for the change. PMID- 8213180 TI - The high-force region of the force-velocity relation in frog skinned muscle fibres. AB - The force-velocity relation has been studied during calcium-induced contracture of chemically skinned fibres from the semitendinosus muscle of Rana temporaria with special interest focused on the high-load region. The force-velocity curve was hyperbolic at low and intermediate loads but departed below the hyperbola as the load exceeded about 80% of the isometric force (P0). The force intercept (P*0) of the hyperbola derived from force-velocity data truncated at 0.78 P0 was higher than P0 (P*0/P0 = 1.14 +/- 0.04). At submaximum Ca2+ concentration, where the isometric force of the fibre was 65-75% of the maximum value, the force velocity data still departed below the hyperbola at high loads (P*0/P0 = 1.09 +/- 0.04). The departure of the force-velocity data from the hyperbola at high force was also found at high ionic strength (250 mM), but not at low ionic strength (150 mM) (P*0/P0 = 1.09 +/- 0.03 and 0.98 +/- 0.03, respectively). The force velocity relations derived under different experimental conditions could be fitted well by a modified version of Hill's (1938) hyperbolic equation (Edman 1988) using similar numerical values of k1 and k2 in the latter equation. The results indicate that the force-velocity relation in skinned muscle fibres is biphasic, and that the two curvatures, as in intact muscle fibres, are closely related to one another. Furthermore the evidence supports the hypothesis that the altered shape of the force-velocity relation at high loads is not related to the force level per se but rather to the speed of shortening of the contractile system (Edman 1992). PMID- 8213181 TI - Effects of metabolic inhibition on cytoplasmic calcium and contraction in smooth muscle of rat portal vein. AB - Contractions in the rat portal vein, evoked by spontaneous action potentials or depolarizing high-K+ solution, are rapidly and reversibly inhibited by hypoxia or respiratory blockade. Intracellular free calcium ([Ca2+]i) was measured using Fura-2 to evaluate the effects of metabolic blockade on excitation-contraction coupling. Spontaneous contractions were associated with transient increases in [Ca2+]i. During exposure to cyanide (0.2-0.4 mM) or 2,4-dinitrophenol (30 microM) the duration and amplitude of the Ca2+ transients were decreased, leading to a decreased mean time integral of the individual [Ca2+]i transient, and corresponding decrease in the duration and amplitude of the contraction. Basal [Ca2+]i was increased in the presence of the metabolic inhibitors. High-K+ (40 mM) contractions caused a sustained increase in [Ca2+]i, which was not inhibited by exposure to cyanide, although the amplitude of the associated contraction was greatly reduced. Together with the earlier demonstration of decreased 20 kD myosin light chain phosphorylation under these conditions, this indicates that the activation of contraction is influenced by metabolism via the energy dependence of the light chain phosphorylation reaction. Thus at least three steps in the excitation-contraction sequence are influenced by inhibition of oxidative metabolism: membrane excitation, light chain phosphorylation, and the cross bridge cycle. This provides mechanisms for a high degree of metabolic sensitivity of vascular tone, of importance for the adaptation of blood flow to tissue metabolic demands. PMID- 8213183 TI - The effect of pressure drop stabilization in arteries during variations in blood flow rate. AB - The aim of this study was to clear up whether the flow-induced dilation of arteries is sufficient to ensure invariability of pressure drop along these vessels under many-fold increase in blood flow rate. In anaesthetized rats an arteriovenous shunt was constructed by connecting the saphenous artery and the femoral vein. Resistance of the shunt was changed by a device creating either rectangular flow pulses of different amplitude or slow linear ramps of flow rate. Pressure drop along the arterial cascade, from the aortic arch up to distal saphenous artery, was recorded and the steady-state flow-pressure drop relationship was determined. At low flow rates (< 0.25-0.3 ml min-1) the pressure drop rose proportionally to flow, i.e. as in a system of ordinary tubes with non regulated diameter. In contrast, at higher flow rates (up to 1.5 ml min-1) the pressure drop either remained unchanged under 3- to 5-fold increases of flow rate or rose far less than the flow. Thus, the pressure drop stabilization effect has been evidenced. The threshold of this effect was about 0.3 ml min-1, corresponding to the 'resting' flow in the saphenous artery, i.e. the narrowest of all the cascade vessels. This coincidence suggests that the pressure drop stabilization is determined by the flow-induced dilation mainly of this artery. PMID- 8213182 TI - In-vivo effects of endothelin-1 and ETA receptor blockade on arterial, venous and capillary functions in skeletal muscle. AB - Results from in vitro studies have indicated that endothelin-1 is a main candidate for endothelium-derived contracting factors. The aim of this in vivo study was to describe in quantitative terms the effects of endothelin-1 (ET-1), and of ETA receptor blockade, on vascular tone (resistance) in large-bore arterial resistance vessels (> 25 microns), small arterioles (< 25 microns) and the veins, as well as on capillary pressure and fluid exchange in cat gastrocnemius muscle. Endothelin-1 (100-1600 ng kg-1 min-1, i.a.) elicited, after an initial transient dilation, a strong dose-dependent constrictor response in all three consecutive vascular sections, yet with a preferential action on the small arterioles and the veins. The vasoconstriction developed very slowly over about 1 h and was also long-lasting after cessation of the infusion. Our main quantitative analysis refers to effects elicited by 20 min long i.a. infusions of ET-1 at a dose of 400 ng kg-1 min-1. At the end of this period, the peptide caused, on average, a three-fold increase in total regional vascular resistance, in turn explained by a 70% increase in large-bore arterial resistance, a 280% increase in arteriolar resistance and a 220% increase in venous resistance. The latter effect was also manifested as a pronounced capacitance response, and as a decrease in the pre- to post-capillary resistance ratio leading regularly to a rise in capillary pressure, net transcapillary fluid filtration and oedema formation which is unusual for a vasoconstrictor. The new specific competitive ETA receptor antagonist FR 139317 was found to be fully effective in vivo, insofar as it abolished the constrictor response to endothelin-1. ETA receptor blockade, or administration of phosphoramidon, an inhibitor of ET-1 production, did not influence the level of basal vascular tone, indicating no significant endogenous release of ET-1 under resting conditions. This contrasts to the established pronounced endogenous release of endothelium-derived nitric oxide. Finally, vascular myogenic regulation was found not to be mediated by ET-1. The results, taken together, suggest a possible role of ET-1 in long-term, rather than short-term, regulation of vascular tone in vivo, perhaps especially during pathophysiological conditions. PMID- 8213184 TI - Endothelium determines stabilization of the pressure drop in arteries. AB - To ascertain whether the relative invariance of the pressure drop along the arterial cascade--from the aortic arch down to include the saphenous artery- during increases of saphenous outflow (Khayutin et al. 1993), is determined mainly by dilation of the latter, and to discover whether this invariability is a manifestation of endothelium-mediated vasodilation, the pressure drop along the rat saphenous artery was measured in situ during exposure of the artery to rectangular pulses or slow ramps of blood flow. At flow rates below a critical value of about 0.3 ml min-1, flow increase was followed by a proportional increase of pressure drop. In contrast, with further flow increase, up to the values five to six times beyond the critical one, the steady state pressure drop did not increase at all, or only to a minor extent. This 'pressure drop stabilization' was shown to be unrelated to the decline of distending pressure, but to result from a true artery dilation commensurate with the flow increase. Interference with the endothelium by way of 90 mM hydrogen peroxide eliminated the stabilization effect, whereas noradrenaline-induced constrictions could be increased about three-fold. The 'threshold' shear stress on the endothelium, needed to initiate saphenous artery dilation, was estimated to be 74 +/- 4 dyn cm 2. The functional importance of stabilizing the pressure drop along the arterial conductance and resistance vessels is discussed. PMID- 8213185 TI - Intense slow hypoxic pulmonary vasoconstriction in gas-filled and liquid-filled lungs: an in vivo study in the rabbit. AB - To examine the hypothesis that hypoxic pulmonary vasoconstriction may have a slower time course and greater intensity than is currently recognized, experiments were conducted in twelve anaesthetized rabbits subjected to unilateral lung hypoxia for 6 h. Endobronchial cannulation was used to maintain apnoea of one lung at constant airway pressure whilst inflating the lung with nitrogen or liquid. The second lung was ventilated with oxygen to maintain normocapnia and oxygen transfer. A pulmonary ventilated with oxygen to maintain normocapnia and oxygen transfer. A pulmonary artery catheter was introduced non invasively. Pulmonary shunt was derived from mixed venous and arterial blood gas parameters. Pulmonary artery pressure was monitored continuously and cardiac output was estimated from oxygen uptake measurements before and after 6 h unilateral hypoxia. The experiments show that a rapid phase of hypoxic pulmonary vasoconstriction is followed by a slow phase which develops over hours. The slow phase is associated with a massive blood flow diversion from the hypoxic lung, such that pulmonary shunt after 6 h unilateral hypoxia is indistinguishable from baseline shunt during bilateral ventilation with oxygen. The response is reversible, but with a similarly slow time course. Results from nitrogen and liquid filling of the lung are similar. These findings are consistent with early experiments by Dirken and Heemstra in 1948 (Quart F Exp Physiol 34, 193-211), and challenge the prevailing notion that hypoxic pulmonary vasoconstriction is always a rapid and relatively weak physiological response to hypoxia. PMID- 8213186 TI - Excitatory and depressant respiratory responses to chemical stimulation of the rostral ventrolateral medulla in the cat. AB - The rostral ventrolateral medulla (rVLM) is known to play an important role in cardiorespiratory control. In the rVLM an 'apnoea region', in which unilateral focal blocks induce strong depressant effects on inspiratory activity up to complete apnoea, has been described. This study was designed to systematically investigate the effects provoked by unilateral micro-injections (10-30 nl) of D,L homocysteic acid 160 mM into this region on respiratory activity and arterial blood pressure in pentobarbitone anaesthetized, vagotomized, paralyzed and artificially ventilated cats. Micro-injections into the rostral portion of this area caused depressant respiratory responses up to complete apnoea, while micro injections into more caudally located sites induced excitatory respiratory responses. Similar effects were observed in the activity of phrenic nerves and inspiration-related medullary neurons of both the dorsal and ventral respiratory group. The respiratory responses could be accompanied by marked increases in blood pressure (> or = 30 mmHg), especially at locations ventral to the retrofacial and facial nucleus; however, they could also occur in the absence of appreciable changes or even in association with slight decreases in blood pressure. Similar respiratory and pressor effects were observed in carotid sinus denervated cats. The results indicate that two distinct rVLM neuronal populations, one located more rostrally and the other more caudally, may have an important role in the genesis and/or maintenance of respiratory rhythm by exerting respectively inhibitory and excitatory influences on inspiratory activity. Furthermore, they support the hypothesis that different neural substrates of the rVLM are involved in the regulation of respiratory and cardiovascular functions. PMID- 8213187 TI - The shivering response during cross-circulation in the common eider duck (Somateria mollissima). AB - The possible role of humoral factors in the control of shivering in the common eider duck (Somateria mollissima) was investigated using a cross-circulation technique. Pairs of animals were coupled so that the arterial system of one animal was connected to the venous system of the other. The rate of blood transferral was 12.8 ml min-1. By adequate heparinization of the extracorporeal blood supply, cross-circulation could be maintained for periods of up to 12 h. The temperature of blood entering each animal Tinlet) was controlled by heat exchangers. During control experiments Tinlet was maintained at a temperature close to normal body temperature. During cooling experiments Tinlet was maintained at c. 20 degrees C. Changes in metabolic heat production and oesophageal temperature in response to blood cooling were measured in cross circulated pairs of animals cooled simultaneously or individually. Based on analysis of the metabolic responses under the different experimental situations, no evidence was found to indicate that blood-borne substances are involved in the shivering response in these animals. PMID- 8213188 TI - Resting oxygen consumption in rats during food restriction, starvation and refeeding. AB - Oxygen consumption was measured in male rats during starvation and during different regimens of restricted feeding and refeeding after starvation. Changes in oxygen consumption and body mass were mostly parallel, but rats with a very reduced food intake displayed the same reduction in oxygen consumption as starved rats, despite the smaller reduction in body mass. Also, rats fed different amounts of food after starvation had different oxygen consumptions, but displayed the same changes in body mass. Two different refeeding regimens with restricted food amounts either induced a further depression of oxygen consumption (i.e. below starvation oxygen consumption), or a stabilizing of oxygen consumption on the level of starvation. The changes in oxygen consumption during restriction and feeding after starvation indicate that reductions in resting metabolic rate may not always be predicted from either body mass change or food intake. PMID- 8213189 TI - A comparative study on the synthesis of dopamine in the human, dog and rat kidney. AB - The present work has examined the ability of human, canine and rat renal tissues to synthesize dopamine from added L-3,4-dihydroxyphenylalanine (L-DOPA); the deamination of newly-formed dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC) was also studied. In some experiments, slices of renal cortex obtained from the human, dog and rat kidneys were used; tissues were incubated with increasing concentrations (5-5000 microM) of L-DOPA. The accumulation of newly-formed dopamine was, in all three species, found to be dependent on the concentration of L-DOPA, being the rat renal tissues endowed with a greater ability to produce dopamine, followed by the human and the dog tissues. In experiments performed in kidney homogenates, the decarboxylation of L-DOPA into dopamine was also found to be dependent, in all three species, on the concentration of L-DOPA used (10-5000 microM). AAAD activity as determined in kidney homogenates was found to be in the rat kidney (Vmax = 7.7 +/- 0.8 nmol mg-1 protein h-1) higher than that occurring in the human (Vmax = 5.8 +/- 0.6 nmol mg-1 protein h-1) and the dog kidney (Vmax = 3.9 +/- 0.5 nmol mg-1 protein h-1). No statistically significant differences were found between the Km values of the three species (human, 62 +/- 8 microM; dog, 54 +/- 6 microM; rat, 82 +/- 12 microM). A considerable amount of newly formed dopamine in both kidney slices and homogenates was converted into DOPAC; the DOPAC/dopamine ratios in these experimental conditions were greater in the human kidney, followed by the rat and dog.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213190 TI - Effect of physical exercise on urinary excretion of CuZn-superoxide dismutase in male high school students. PMID- 8213191 TI - Effects of hyperoxia on bronchial wall dimensions and lung mechanics in rats. AB - The effects of exposure to hyperoxic conditions (> 95 kPa at normobaric pressure) on bronchial wall dimensions and lung mechanics were examined in adult rats. Measurements of baseline pulmonary resistance and changes in pulmonary resistance following acetylcholine aerosol inhalation were made in rats exposed to hyperoxia for 48 and 60 h and in control rats exposed to air. Exposures for 48 h were carried out in humid (80% relative humidity) or dry (35-40% relative humidity) conditions. Morphometric measurements of airway wall thickness in lobar bronchi were made in separate groups of similarly exposed rats. Exposure to hyperoxia was associated with an increase in baseline pulmonary resistance (control rats 0.043 (0.016) cmH2O ml-1 s-1, 60 h exposed rats 0.125 (0.042) cmH2O ml-1 s-1) but hyper responsiveness to acetylcholine inhalation did not occur. Thickness of the airway wall and its subdivisions, epithelium, lamina propria and muscularis, was not altered by hyperoxic exposure in humid conditions. However, epithelial thickening in the lobar bronchi was observed in rats exposed for 48 h to hyperoxia in dry conditions compared to rats exposed in humid conditions (mean (SD) thickness 13.2 (3.3) microns for controls, 14.5 (1.5) microns for humid exposed rats and 16.5 (3.3) microns for dry exposed rats). The increase in pulmonary resistance caused by hyperoxic exposure is unlikely to be due to airway damage as airway hyper responsiveness did not occur, and is more likely to be associated with the development of alveolar oedema. Environmental humidity may modulate lung damage induced by hyperoxia, as exposure in dry conditions was associated with significant epithelial thickening. PMID- 8213192 TI - Pulmonary function hysteresis during compression to, and decompression from 31.3 ATA. AB - Tracheal gas density breathing heliox at 31.3 atmospheres absolute (O2 at 0.42 ATA) is 6.287 g l-1, or approximately 5.5 times greater than air at 1 ATA. This constitutes a significant respiratory load, previously shown to induce respiratory adaptation. During a saturation dive to 31.3 ATA, five divers were exposed to this load for 16 days. This project aimed at investigating possible hysteresis in pulmonary function during dive compression, adaptation and decompression phases. Pulmonary function tests were performed at the surface in air, and at four pressure stops during compression and decompression, with divers breathing the helium-oxygen gas mixture. Significant hysteresis patterns were observed for pooled maximal voluntary ventilation, forced expired volume at 1 s, peak expiratory flow, and maximum expiratory flows (P < 0.05), with post adaptation flows consistently exceeding those observed during compression. Two mechanisms may explain these observations. Differences may be attributable to positive effort-dependence in the forced expiratory flow; or it is possible the subjects adapted to the respiratory load by modifying neural input to airway smooth muscle, thereby modifying airway resistance. PMID- 8213193 TI - Changes in lower limb muscle cross-sectional area and tissue fluid volume after transition from standing to supine. AB - Lower limbs show acute fluid shift in response to transition from upright to supine body position. It is hypothesized that this would affect tomographic estimations of muscle mass and composition. Seven healthy subjects were investigated during the initial 120 min of bed rest, using repeated computerized tomography (CT) and continuous bioelectrical impedance analysis (BIA). Thigh and calf muscle cross-sectional area (CSA) decreased (P < 0.05) by 1.9 and 5.5% whereas fat CSA decreased (P < 0.05) by 4.1 and 4.4%, respectively. Radiological density (RD) of muscle showed a simultaneous increase (P < 0.05) by 4.8% in calf but not (P > 0.05) in thigh. No changes occurred (P > 0.05) in muscle or fat CSA or muscle RD in either thigh or calf between the first and second hour of bed rest. Fluid shift, as estimated by BIA, showed an exponential decay in thigh (tau th = 30 min) and calf (tau c2 = 37 min) by 2.5 and 8.7%, respectively, from first to 120 min of bed rest. Moreover, the calf showed an initial rapid (tau c1 = 8 s) 2.2% decrease. The demonstrated short-term changes in leg CSA were more pronounced in the calf than in the thigh. They were similar in muscle and subcutaneous fat. These fluid shifts merit consideration when tomographic imaging techniques are used to estimate muscle mass and composition. PMID- 8213194 TI - Transcellular fluid secretion induced by cholera toxin and vasoactive intestinal polypeptide in the small intestine of the rat. AB - The permeation of intravenously administered 51Cr-EDTA and [14C]mannitol to the perfused intestinal lumen was measured in anaesthetized rats together with the net intestinal fluid. Net fluid secretion was induced by cholera toxin or by intravenous infusion of vasoactive intestinal polypeptide (VIP). The plasma clearance of Cr-EDTA and mannitol was 0.9 +/- 0.1 and 1.4 +/- 0.2 microliters min 1 g-1 intestine during the control period prior to the secretion and the net fluid absorption was about 7 +/- 5 microliters min-1 g-1. Cholera toxin induced a net fluid secretion of about 30 +/- 7 microliters min-1 g-1 but the clearance did not rise but decreased significantly. The findings for VIP-induced secretion were similar. No indication of solvent drag was seen. Thus it is concluded that the fluid was secreted in channels which were smaller than the probes and we propose that the secreted fluid entered the intestinal lumen through the epithelial cells and not by the paracellular route. The decreased permeation of Cr-EDTA and mannitol from plasma to lumen during volume secretion suggest that there was a decreased mucosal permeability during the secretion. The decrease in permeability was consistent with a decrease in pore size. One explanation of the data is that the pore radius contracted from about 35 to 15 A during cholera if we assume a homogenous pore population. However, the data indicated that there was not a uniform size of the pore.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213195 TI - In vivo regulation of mucosal transport of H+ and HCO3- in the feline gall bladder. AB - In the gall bladder of a fasting subject, a decline in the pH of the contents occurs due to secretion of H+ from the mucosa. In this study in anaesthetized cats, the gall bladder lumen was perfused with a bicarbonate buffer bubbled with 4% CO2 in air. During basal conditions, the PCO2 always rose while the pH and [HCO3-] fell in the buffer when passing through the gall bladder lumen, indicating a continuous secretion of H+ by the mucosa. This H+ secretion was enhanced by stimulation of the respective sympathetic nerves and was blocked by intraluminal amiloride. Intravenous infusion of vasoactive intestinal peptide (VIP) raised the pH and [HCO3-] in the buffer during the passage through the gall bladder lumen, indicating a secretion of bicarbonate from the mucosa. In view of the presence of sympathetic and VIP immunoreactive nerve fibres in the gall bladder wall and VIP receptors on the luminal epithelial cells, the study demonstrates that there are functional grounds for physiological variations in the secretion of H+ and HCO3- by the gall bladder mucosa. These variations may be important for the solubility of calcium salts in the gall bladder contents. PMID- 8213196 TI - Plasma oxytocin, prolactin, insulin and LH after 24 h of fasting and after refeeding in lactating sows. AB - The effects of 24 h of fasting and refeeding on the release of oxytocin, prolactin, insulin and LH in three lactating sows were investigated. The sows were starved, but supplied with water ad libitum, from 09.00 h on day 27 of lactation until 15.00 h on day 28 of lactation, when they were refed. Blood samples were collected continuously, using an automatic collection system, at a rate of 1 ml min-1 from 09.00 to 21.00 h on day 28 (P1 = 6 h period after the 24 h fast, P2 = 6 h period after refeeding). For both P1 and P2 the mean number of nursings was 7.0 +/- 1.0. Plasma insulin and glucose decreased to very low levels during fasting and increased (P < 0.001) after refeeding (insulin, 2.5 +/- 0.7 vs. 28.9 +/- 0.7 mU l-1; glucose, 2.6 +/- 0.3 vs. 6.4 +/- 0.3 mmol l-1). Following fasting, levels of prolactin were low (2.8 +/- 0.1 micrograms l-1), and sucking did not induce significant release of prolactin. However, prolactin increased rapidly after refeeding (5.4 +/- 0.1 micrograms l-1, P < 0.001). Neither the 24 h fast nor refeeding had a marked effect on basal levels of oxytocin, the percentage of sucklings with an oxytocin peak or the size of oxytocin peak. LH release (average and basal levels and number of pulses/6 h) during fasting was similar to that measured after refeeding. Plasma CCK increased significantly after feeding. The results indicate that the release of prolactin is also regulated by feed intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213197 TI - The L-arginine/nitric oxide pathway in the rabbit urethral lamina propria. AB - A non-adrenergic, non-cholinergic (NANC)-mediated relaxation has been demonstrated in the female rabbit urethral lamina propria, both in response to electrical stimulation and after administration of acetylcholine. The present study was performed to investigate if these relaxations are mediated via the L arginine/nitric oxide (NO) pathway. In the lamina propria of the female rabbit urethra, numerous NADPH diaphorase-positive, fine varicose nerve fibres were observed both around arteries, in and around smooth muscle bundles, and in arterial endothelium. Since NADPH diaphorase histochemistry may be a marker of NO synthase-containing neurons, this finding suggests the occurrence of NO synthase in this tissue. Isolated preparations of the rabbit urethral lamina propria, contracted by noradrenaline, produced frequency-dependent NANC relaxations in response to electrical field stimulation, and concentration-dependent NANC relaxations in response to acetylcholine. Electrically induced relaxations were possible to evoke even in preparations where acetylcholine-induced relaxation was poor or absent. Pretreatment with the NO synthase inhibitor, NG-nitro-L-arginine (L-NOARG) reduced the maximum relaxation obtained at 30 Hz to 12% of the control response. NG-nitro-D-arginine (D-NOARG) had no effect. The effects of L-NOARG were antagonized by the addition of L-arginine. Acetylcholine relaxed noradrenaline-precontracted strips by 36%; vasoactive intestinal polypeptide (VIP) reduced the contraction by 95%. L-NOARG, but not D-NOARG, abolished or reversed acetylcholine-induced relaxations, but failed to reduce the relaxations produced by VIP. The results demonstrate the occurrence of NADPH diaphorase positive nerve fibres in the lamina propria of the female rabbit urethra.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213198 TI - A study of cholinergic and beta-adrenergic components in the regulation of blood flow in the tooth pulp and gingiva in man. AB - In 10 subjects, laser Doppler flowmetry was used to study whether cholinergic or beta-adrenergic pathways are involved in the control of tooth pulp blood flow (PBF) in response to isometric hand grip and the cold pressor test. We also examined if differences exist between the regulation of blood flow in the tooth pulp and the nearby gingiva (GBF). Isometric hand grip (35% of maximum force, 2 min) and the subsequent ischaemia (2 min) induced a brief rise in PBF and a more long-lasting rise in GBF. Atropine increased heart rate about by 40% and changed the pulpal response to a fall in flow, without altering gingival flow. Propranolol, causing a 20% reduction in heart rate, had no effect on either flow during the actual test, but induced a rise in GBF after the ischaemic period. The cold pressor test (2 min at 0.5 degrees C) resulted in a reduction in PBF and GBF, unaffected by the blocking drugs. With atropine, however, PBF increased immediately after this test. The relative changes in arterial pressure and heart rate were unaffected by the drugs. Our study has demonstrated the existence of cholinergic nervous vasodilation in vessels serving the tooth pulp. Non adrenergic non-cholinergic mechanisms probably contribute to the evoked rise in GBF during exercise. Beta-adrenoceptors are involved in the control of GBF immediately after isometric exercise. While the two tests under control conditions evoked mostly parallel changes in PBF and GBF, the use of blocking agents showed that blood flow is controlled by different mechanisms in the two adjacent vascular beds. PMID- 8213199 TI - Effects of nitric oxide synthesis blockade and angiotensin II on blood flow and spontaneous vasomotion in the rat cerebral microcirculation. AB - The effects of N omega-nitro-L-arginine methyl ester (L-NAME) an inhibitor of NO synthesis, or angiotensin II on the frequency and amplitude of rhythmic variations (vasomotion) in blood flow of the intact rat cerebral circulation were investigated using laser-Doppler flowmetry (LDF). Experiments were performed on Sprague-Dawley rats anaesthetized with alpha-chloralose. The rat's head was fixed on a stereotaxic frame and the microvascular blood flow of the parietal cortex on the right or on both sides was measured via a small hole in the parietal bone, keeping the dura and a thin bone layer intact. Following the intravenous injection of L-NAME, the mean arterial blood pressure (MABP) increased to 123 +/- 1 mmHg (1.25 mg kg-1) or to 144 +/- 3 mmHg (5.0 mg kg-1) but no significant changes in cerebral blood flow (CBF) or vasomotion could be detected. The observed increase in MABP was sustained until L-arginine was administered. In the presence of L-NAME, during stepwise reduction of MABP, CBF remained constant when MABP was kept between 60 and 130 mmHg, the vasomotion frequency was lower when MABP was above 80 mmHg but its amplitude was two times higher than in the control group. In another group of animals, angiotensin was infused to give comparable increments in blood pressure. In contrast to L-NAME, angiotensin II had no effect on either frequency or amplitude of vasomotion, compared to the control group, within the whole range of MABP studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213200 TI - Non-uniformity of two-dimensional myocardial deformation in response to chronotropic and inotropic stimulation in cats. AB - The degree of uniformity of myocardial deformation for cross-oriented segments in the anterior wall of the left ventricle is influenced both by loading conditions and by infusion of isoprenaline. The aim of this study was to clarify the chronotropic influence (atrial pacing) compared to the combined inotropic and chronotropic effects of isoprenaline on uniformity of contraction. In eight open chest pentobarbitone-anaesthetized cats segment performance was measured by orthogonal sonomicrometry. Heart rate (HR) increased from control state, 199 +/- 5 (mean +/- SEM) beats min-1, to 224 +/- 6 and 227 +/- 7 beats min-1 during atrial pacing and isoprenaline infusion, respectively (P < 0.0005). Circumferential segment shortening remained unchanged during pacing but increased with isoprenaline (P < 0.0005). Longitudinal segments showed reduced shortening during pacing (P < 0.05), whereas shortening during isoprenaline infusion did not differ from control shortening. The ratio between shortening of longitudinal and circumferential segments, long/circ ratio, changed from 0.52 +/- 0.13 in the control state to 0.36 +/- 0.10 during pacing and 0.39 +/- 0.11 with isoprenaline (P < 0.05). End-systolic pressure-length relations were unchanged by atrial pacing but showed leftward shifts during isoprenaline infusion. Myocardial tissue blood flow (microspheres) was unchanged during interventions. We conclude that both atrial pacing and isoprenaline infusion lead to a more non-uniform deformation in the anterior wall. However, non-uniformity during atrial pacing was primarily related to reduced longitudinal shortening whereas the non uniformity during isoprenaline infusion was due to increased circumferential shortening. PMID- 8213201 TI - (R)-8-OH-DPAT preferentially increases dopamine release in rat medial prefrontal cortex. PMID- 8213202 TI - Suitability for brief dynamic psychotherapy: psychodynamic variables as predictors of outcome. AB - The success rate in predicting symptom change 2 years after brief dynamic psychotherapy increased 20% by adding quality of interpersonal relations from a psychodynamic evaluation interview to DSM-III diagnoses, Axis V and Axis II. The success rate in predicting dynamic change 4 years after therapy increased nearly 40% by adding the same variable. Selection criteria such as circumscribed focus, motivation and involvement in the evaluation interview were shown to be redundant as predictors. PMID- 8213204 TI - Patterns of treatment resistance in bipolar affective disorder. AB - The mean index episode length in 19 consecutive admissions with treatment resistant bipolar affective disorder was 21.7 months. Four patterns of resistance were identified: rapid cycling (37%), other forms of cycling (32%), chronic depression (26%) and mixed states (6%). Female gender was significantly associated with rapid cycling. Other risk factors for treatment-resistant bipolar disorder, including a high prevalence of family history of affective disorder (72%) and electroencephalographic abnormalities (54% of recordings), were not confined to the rapid cycling group. PMID- 8213203 TI - Characteristics of winter depression in the Oslo area (60 degrees N). AB - This is the first comprehensive description of winter depression (WD), as part of seasonal affective disorder (SAD), from Norway, and one of the very few from so far north. A total of 128 media-recruited people had first been screened with the Seasonal Pattern Assessment Questionnaire and were thereafter personally interviewed. The criteria for DSM-III-R mood disorder, seasonal pattern, were satisfied by 85%, whereas 73% satisfied the criteria of Rosenthal et al. for SAD. Seven percent were diagnosed as subsyndromal SAD. The main characteristics of our patient group were in reasonable accordance with other clinical SAD materials: there were 81% women; the mean age was 44 years (range: 20 to 76); the mean age for SAD debut was 24 years (range: 4 to 71); and the duration of WD was most often from October to March or April. Only 12% had ever been manic or hypomanic in summer. During their WD, most patients suffered at least one of the symptoms hypersomnia, hyperphagia or carbohydrate craving; 16% also had a craving for fatty food in winter, but this may be considered "normal" at this northerly latitude. PMID- 8213205 TI - A second labour market? Vocational rehabilitation and work integration of chronically mentally ill people in Germany. AB - In Germany, the vocational rehabilitation of chronically mentally ill people is concentrated on the sheltered labour market, supplemented by special programmes for the care and reintegration of mentally ill people on the open labour market. Our investigation covered 502 representatively selected patients in sheltered employment (outpatient work therapy, firms for mentally ill people, workshops for the disabled). The sociodemographic, anamnestic and psychopathological data reveal that these are chronically mentally ill people with significant disabilities, making comprehensive social care and psychiatric treatment essential. Most of the subjects intend to remain in sheltered employment; only 20% hope to change to the open labour market. The level of subjective job satisfaction is surprisingly high despite generally inadequate pay, though it has to be pointed out that many long-term patients are presumably resigned to their circumstances. In conclusion, the relationship of the open labour market to sheltered employment is the subject of critical discussion. PMID- 8213206 TI - Atrial natriuretic peptide and arginine vasopressin secretion in schizophrenic patients. AB - Plasma levels of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) were measured in 15 patients with schizophrenic or schizoaffective disorders and 15 healthy volunteers during oral water loading at 20 ml/kg. In the patient group, plasma AVP was secreted even when plasma osmolality was below 270 mosmol/kg, although the sensitivity of AVP secretion response to osmolality was lower than in the controls. The ANP level was higher in the group of patients than in the controls. There was a negative correlation between plasma ANP and osmolality in the patients. We speculate that the volume expansion caused by inappropriate AVP secretion stimulated plasma ANP release and that the natriuresis resulting from the elevated plasma ANP level might contribute to hyponatremia. PMID- 8213207 TI - Gender specificity of geographical variation in morbid risk for schizophrenia in rural Ireland. AB - The morbid risk for schizophrenia was determined separately for men and women within each of 36 contiguous district electoral divisions of a rural Irish county in which all cases of schizophrenia satisfying DSM-III-R criteria had been sought. The distribution of morbid risk values for men (0.0-19.2 per 1000) was in accordance with a statistical model for random occurrences in space, while for women (0.0-38.3 per 1000) it deviated markedly from such a model; thus, morbid risk for schizophrenia showed very prominent geographical variations in women, but not in men. These findings may have a basis in factors that can show both spatial inhomogeneity and gender specificity in their consequences for schizophrenia. PMID- 8213208 TI - Disparity in regional cerebral blood flow during electrically induced seizure. AB - This is a presentation of 2 cases in which the intraictal regional cerebral blood flow distribution was measured with the 99mTc-HMPAO single photon emission computerized tomography technique during an electrically induced seizure. Although the seizure was verified as generalized on electroencephalography, the regional neuronal activity expressed as rCBF unexpectedly was markedly asymmetrical in one of the cases. These findings demonstrated that the 99mTc HMPAO technique makes it possible to discriminate intraictal variation in cortical and subcortical activation between the hemispheres during electroencephalography-verified generalized seizures. PMID- 8213209 TI - Disqualifying family communication and anxiety in offspring at risk for psychopathology. AB - The association between disqualifications in parental and family communication and manifest anxiety in boys (7 or 10 years) was investigated. The sample consisted of 59 families where one of the parents had previously been hospitalized for a functional mental disorder. Parental and family communication was observed in the Couples Rorschach (CR) and Family Rorschach (FR) tasks, respectively. The results showed that the amount of one particular type of disqualification, self-disqualification, correlated positively with the boy's anxiety level. Self-disqualification refers to utterances in which the speaker communicates in vague, egocentric or paradoxical ways, which makes it impossible for the receiver to know what has been said. This correlation was evident both with respect to the communication between the parents during CR and the communication from the family to the index boy during FR. The relationship between self-disqualification and anxiety was attributable to neither the boy's age or intelligence quotient nor the dimensions of parental psychopathology or functional impairment. PMID- 8213210 TI - Thiamine pyrophosphate effect and erythrocyte transketolase activity during severe alcohol withdrawal syndrome. AB - The thiamine pyrophosphate (TPP) effect and erythrocyte transketolase activity (ETKA) in a group of 28 patients admitted to a psychiatric emergency ward because of severe alcohol withdrawal syndrome were compared with the TPP effect and ETKA in a control group of 20 healthy nonalcoholic volunteers. The patients were treated with 300 mg thiamine 3 times daily as intramuscular injections, and the TPP effect and ETKA were measured after 1 and 4 days of treatment. No difference was found between the patient group and the control group with regard to the TPP effect and ETKA and no decline in the TPP effect was found in the patient group after 4 days of intensive treatment with thiamine. ETKA increased with intensive thiamine treatment, which suggests that ETKA is a sensitive indicator of thiamine deficiency. Serum magnesium, which is a cofactor for thiamine pyrophosphate, decreased significantly with the disappearance of alcohol from the blood in patients with high initial blood alcohol levels, but this shift did not interfere with biological thiamine activity. PMID- 8213211 TI - A twin study of DSM-III-R anxiety disorders. AB - The prevalence of anxiety disorders was studied in a sample of 20 monozygotic (MZ) and 29 dizygotic (DZ) co-twins of anxiety disorder probands. A comparison group of co-twins of 12 MZ and 20 DZ twin probands with other non-psychotic mental disorders was also studied. All subjects were personally interviewed with the Structured Clinical Interview for DSM-III-R Axis I (SCID-I). Panic disorder was significantly more prevalent in co-twins of panic probands. Generalized anxiety disorder (GAD) was more prevalent in co-twins of GAD probands with a history of mood disorder (NS). Post-traumatic stress disorder was significantly more prevalent in co-twins of anxiety probands and was more prevalent in MZ than in DZ co-twins. The prevalences of social and simple phobia were equal in co twins of anxiety and comparison probands. For both panic disorder and generalized anxiety disorder the MZ:DZ concordance ratio was more than 2:1. The results support the hypothesis of a genetic contribution in the etiology of panic disorder, generalized anxiety disorder and post-traumatic stress disorder. The hypothesis that simple and social phobia are mainly caused by environmental experiences was also supported. PMID- 8213212 TI - The consequences of an open referral system to a community mental health service. AB - The first 590 patients referred to a community mental health service (the Early Intervention Service) in an inner-city district were separated into groups based on their referral source. The service has an open referral system allowing any agency (including patients) to contact the service by letter or by telephone, and priority is given to patients with serious mental illness. The results of open referral showed that the number of referrals was adequate for the service to process, the proportion of inappropriate referrals was similar in all referral agencies, and milder cases of mental illness were referred more often from doctors than from other agencies. It is concluded that an open referral system is likely to be more sensitive to need and has some advantage over closed referral arrangements in inner-city areas. PMID- 8213213 TI - The effect of visual similarity on short-term memory for spatial location: implications for the capacity of visual short-term memory. AB - Evidence from the recency effect suggests that visual short-term memory is limited to preserving information about a single pattern. Three experiments explored the capacity of visual short-term memory using a task which involved presenting a series of patterns in a random spatio-temporal sequence and probing memory for the spatial location of one of them. Experiment 1 used sequences of quasi-random block patterns which were either visually similar or dissimilar. Serial position curves showed a single-item recency effect. However, there was also a deleterious effect of visual similarity for the earlier patterns, indicating that visual short-term memory was supporting their retention. Experiment 2 showed that performance was unaffected by articulatory suppression, confirming that phonological coding is not an important factor in the localisation task. Experiment 3 switched to letter stimuli and, because of the known tendency for this type of stimulus to be phonologically recoded, required articulatory suppression. Letters were shown in a customised form in sequences which were either visually similar or visually dissimilar. The results replicated experiment 1 in showing restricted recency combined with an effect of visual similarity extending across earlier list items. When the same letters were shown in standard form, the recency effect remained but the similarity effect disappeared, ruling out possible interpretations in terms of semantic as well as phonological coding. It is concluded that the recency effect gives a misleading indication of the capacity of visual short-term memory. The visual similarity effect suggests that it is capable of supporting the retention of several patterns. PMID- 8213214 TI - Inattention and the perception of visual features. AB - Subjects selectively attended to one of two interleaved, novel figures while ignoring the other figure. In subsequent tests administered to determine the extent to which the ignored figure was perceived, recognition of shape and the location of contour gaps was at the chance level. Moreover, recognition of the presence of contour gaps was significantly below the chance level. These results indicate that preattentive visual processing of unattended objects is too crude to encode global shape and local features such as contour gaps. It is suggested that preattentive processing creates visual representations of unattended objects that contain very limited information about features. PMID- 8213215 TI - Elevated lipid peroxidation, decreased glutathione levels and changes in glutathione-related enzymes in rats treated with human placental extract. AB - The in vivo effects of human placental extract (1-4 ml/kg) on hepatic lipid peroxidation, blood and liver glutathione (GSH) levels and several enzymes associated with the antioxidant defence mechanism; i.e., catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, together with some blood biochemical responses were investigated in rats. At an optimal dose level (4 ml/kg), a single acute intraperitoneal administration of the extract caused a significant enhancement (49.9%; p < 0.001) of lipid peroxidation with a decline in GSH level both in blood (45.1%; p < 0.001) and liver (61.0%; p < 0.001) in comparison to control animals. Activities of catalase, glutathione peroxidase and glutathione reductase were inhibited in a dose-responsive way by the treatment with the extract which also increased the activity of glutathione S transferase in a dose-dependent manner. The extract was found to be hepatotoxic in terms of elevation of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum lactate dehydrogenase and blood methemoglobin concentration. Results of this study suggest the adverse consequences of the administration of the extract due to its substantial ability to alter normal cellular processes. PMID- 8213216 TI - Cell-mediated immunity in bronchial asthma evaluated by purified protein derivative- and Candida albicans-skin reaction. AB - Cell-mediated immunity was examined in 45 patients with bronchial asthma by observing the delayed cutaneous reaction to purified protein derivative (PPD) and Candida albicans (C. albicans). The delayed skin reaction to PPD showed a decrease with age starting between 50 and 59 years old. The delayed reaction to PPD decreased more prominently with aging, being significantly depressed in the patients aged over 70 years than in those aged between 30 and 49 years (induration, p < 0.02; flare, p < 0.01). The C. albicans-induced skin reaction was significantly lower in the patients aged over 70 years than in those between 60 and 69 years old (induration, p < 0.01; flare, p < 0.05). The delayed skin reaction to PPD and C. albicans was significantly depressed in the patients with a serum IgE level over 1001 IU/ml. Delayed skin reaction to PPD and C. albicans was more depressed with aging and an elevated serum IgE, and the age (50-59 years) at the initiation of depression in the PPD-induced delayed skin reaction was younger than that (over 70 years) in the C. albicans-induced reaction. PMID- 8213217 TI - Antitumor activity of platinum analogs against human lung cancer cell lines and tumor specimens. AB - Antitumor activities of five platinum analogs, including cisplatin, carboplatin, 254-S, DWA2114R, and NK121, were compared using five human lung cancer cell lines and 19 tumor specimens obtained from lung cancer patients. The antitumor activity was evaluated by determining the ratio of the maximum tolerated dose of each drug to the 70% tumor growth inhibitory concentration in a colony assay. Cisplatin was the most potent agent, followed by 254-S and carboplatin. DWA2114R and NK121 were less potent than cisplatin and 254-S. Cross-resistance to adriamycin was also investigated using an adriamycin-resistant small cell lung cancer subline, SBC 3/ADM30. SBC-3/ADM30 was 1.7- to 4.0-fold more resistant to cisplatin, carboplatin, NK121, and DWA2114R, than was the parent line, SBC-3, and the subline was 2.0-fold more sensitive to 254-S. Using SBC-3, in vitro combination effects of etoposide and cisplatin, carboplatin, or 254-S were evaluated by the median-effect principle. Synergism was noted when cisplatin and etoposide were combined at a fixed molar ratio of 1:1. Combination of carboplatin and etoposide showed an additive effect. The combination of 254-S and etoposide was antagonistic at low concentrations, but was markedly synergistic at higher concentrations. These data suggested the efficacy of 254-S in the treatment of lung cancer. PMID- 8213218 TI - MDR1 gene expression and treatment outcome in small cell lung cancer: MDR1 gene expression as an independent prognostic factor. AB - We report a preliminary study to determine whether MDR1 gene expression level in small cell lung cancer (SCLC) tumors is a useful predictor of tumor response to chemotherapy and patient survival in association with myc amplification in the tumor. We analyzed 18 patients with SCLC receiving adriamycin and etoposide combination chemotherapy between August 1989 and November 1991; 16 males and 2 females, median age of 68 years, and 7 with limited disease and 11 with extensive disease. MDR1 mRNA expression level and myc family gene amplification were simultaneously determined by polymerase chain reaction using transbronchial biopsy specimens which were obtained at diagnosis. Patients with tumors expressing low MDR1 mRNA responded more favorably to chemotherapy than those with tumors expressing high MDRI mRNA, however, the difference in tumor response was statistically not significant (84.6% versus 40%). The overall survival was significantly shorter in the latter than in the former (7.2 months versus 11.7 months; p = 0.023). The survival of the 4 patients with tumor showing myc family gene amplification was almost identical to that of patients with tumors showing no amplification of the gene (8.2 months versus 8.8 months; p = 0.73). Multivariate Cox's regression analysis supports the notion that MDR1 may be a useful independent prognostic factor. PMID- 8213219 TI - Hyperthermotherapy for postoperative local recurrences of rectal cancer. AB - Between November 1984 and August 1992 we used hyperthermotherapy in six cases of local recurrence of rectal cancer. Hyperthermotherapy was performed on the average 8.7 times (range: 3-18) for each patient for 60 min each. All patients underwent combined radiotherapy and received a mean radiation dose of 42.5 Gy (range: 9-60 Gy). Five patients underwent heating within 1 h after irradiation and one patient simultaneously with the irradiation. Four patients underwent combined chemotherapy and two patients immunotherapy. Before the treatment all patients had painful lesions, but pain decreased posttherapeutically in five patients. Performance status improved in two patients. High carcinoembryonic antigen levels prior to the therapy in four patients decreased in all cases after treatment. Posttherapeutical computed tomograms revealed only minor response or no changes. After the treatment, four patients died of exacerbations of recurrent tumors and one patient of distant metastases. The patient who underwent simultaneous radiohyperthermotherapy is presently alive, in August 1992, 38 months after initiation of the treatment. The 50% survival time after initiation of the treatment was 25 months (range: 10-38 months). Hyperthermotherapy combined with radiotherapy, chemotherapy and/or immunotherapy was useful for the alleviation of pain in patients who developed local recurrence after surgery, and improved survival after recurrences can be expected. PMID- 8213220 TI - A study on cross-reactivity of anti-DNA antibody with glycosaminoglycans. AB - To study the pathogenesis of lupus nephritis, the cross reactivity between anti DNA antibody and glycosaminoglycans (GAGs) was investigated. Monoclonal anti-DNA antibodies were obtained from hybridomas by the fusion of MRL/lpr/lpr splenocytes with murine myeloma cells. Some of these monoclonal anti-DNA antibodies showed cross reactivity with GAGs, such as hyaluronic acid, chondroitin sulfate and heparan sulfate. To elucidate the mechanism of cross reactivity, inhibition assays with propanol and polyethylenimine (PEI), a cationic agent, were carried out. Increase of the concentration of PEI (0.6-2.0% vol/vol) resulted in a dose dependent decrease in the binding ability of anti-DNA antibody to GAGs. Propanol, an organic reagent which disrupts the van der Waals bonds between epitopes and paratopes, showed little inhibitory effect on the binding activity of monoclonal anti-DNA antibody to GAGs. These results indicate that the binding of anti-DNA antibody to GAGs is due to a charge interaction rather than van der Waals forces. Anti-DNA antibody which can react with GAGs in the glomerular basement membrane seems to play an important role in the pathogenesis of lupus nephritis. PMID- 8213221 TI - Mid-term results of bilateral internal thoracic artery grafting. AB - Forty patients underwent coronary revascularization using bilateral internal thoracic artery (ITA) grafts between 1988 and 1992. A total of 111 coronary grafts were performed, or an average of 2.8 grafts per patient. Each patient received bilateral ITA grafts, and in 20 patients an additional 29 grafts were constructed with 18 autologous veins and 11 gastroepiploic arteries. The right ITA was grafted as a free graft in 20 patients. The ITA graft patency rate was 96 per cent (67/70) at the time of hospital discharge. The operative morbidity included 3 reoperations for bleeding, 1 perioperative myocardial infarction, 1 renal failure, 2 postcardiotomy shock, and 1 colon perforation. Two hospital deaths occurred; one due to colon perforation and the other due to postcardiotomy cardiogenic shock. One patient died of cerebral infarction 6 month after the operation. Thirty-four patients were in New York Heart Association functional class I, 2 were in class II and 1 was in class III. Cardiac function evaluated by echocardiography and scintigraphy showed significant improvement postoperatively. These data suggest that the use of bilateral ITA grafts is associated with an acceptable mortality and increases the versatility of arterial grafting. PMID- 8213222 TI - Neural cell adhesion molecule expression and clinical features in small cell lung cancer: a semi-quantitative immunohistochemical approach using an immunogold silver staining method. AB - The neural cell adhesion molecule (NCAM) is a family of cell surface sialoglycoproteins mediating homotypic and heterotypic cell-cell adhesion. In tumors, NCAM is supposed to be involved with the malignant features characterized by invasive growth and metastasis. In the present study, we evaluated the correlation between NCAM expression of tumors obtained from small cell lung cancer (SCLC) patients and the clinical outcome. NCAM expression was determined semi-quantitatively by an immunogold-silver staining method using the SCLC cluster 1 monoclonal antibody NCC-LU-243. Of 20 SCLC patients studied, six patients with tumors with high NCAM expression had a poor response to chemotherapy, and a short disease-free (p = 0.011) and overall (p = 0.003) survival as compared with 14 patients having tumors with low NCAM expression. These findings indicate that the therapeutic outcome of SCLC may be partly predicted by determining the NCAM expression of the tumor. PMID- 8213223 TI - Assessment of bioavailability of oral micronized progesterone using a salivary progesterone enzymeimmunoassay. AB - Salivary progesterone was measured sequentially by enzymeimmunoassay following 1 month and 6 months of oral therapy with 100 mg of micronized progesterone (MOP) in 40 healthy estrogenized postmenopausal women (aged 40-68 years). MOP was administered for 23 days every month. There were striking differences in the absorption of MOP between various subjects. Significant increases occurred in salivary progesterone concentrations over baseline and pretreatment levels and persisted for at least 10 h. Levels of salivary progesterone remained higher than pretreatment levels for at least 24 h after administration of MOP. Maximum mean concentrations of salivary progesterone of 827.2 and 888 pmol/l in the 1st and 6th months of therapy, respectively, were achieved within 2 h of administration and were above the 95th percentile of a control corridor which corresponds to the range found in the luteal phase. The areas under the salivary progesterone curve (AUC0-24 h, pmol/l) were 7177.75 and 7388.20 respectively, in the 1st and 6th months of therapy but the difference was not statistically significant. Serum and salivary progesterone peaked simultaneously and there was a significant correlation between the concentrations measured concurrently (y = 233.08 + 35.575x; r = 0.89, p < 0.001) thus supporting the current concept of a relatively rapid diffusion of steroids from plasma to saliva. Results of this study confirm those of previous investigations which monitored the bioavailability of MOP with the use of serum progesterone measurements and showed that luteal phase progesterone concentrations can be attained easily. The use of non-invasive salivary sampling and a cost-effective, direct enzymeimmunoassay showed a considerable advantage in the present study, compared with previous ones. We conclude that 100 mg MOP should be given at least twice-daily to maintain a stable physiological luteal phase level of progesterone during clinical hormone replacement therapy. PMID- 8213224 TI - Liver metabolism during treatment with estradiol and natural progesterone. AB - Serum concentrations of sex hormone-binding globulin (SHBG), corticosteroid binding globulin (CBG), ceruloplasmin, lipoprotein A and liver enzymes were measured in 30 postmenopausal women treated with 2 mg micronized 17 beta estradiol daily and micronized progesterone orally in doses of 50, 100 and 200 mg daily, as progestogen supplementation. The treatment lasted for 4 months. The serum levels of SHBG and CBG increased during treatment and a weak association between progesterone dosage and CBG was observed. Levels of lipoprotein A and liver enzymes did not change. It is concluded that micronized natural progesterone is an attractive means of progesterone supplementation in postmenopausal hormone replacement therapy without any liver-related side effects. PMID- 8213225 TI - Comparison of hCG versus GnRH analog for releasing oocytes following ultra low dose gonadotropin stimulation. AB - Previous data have suggested there is a higher incidence of luteinized unruptured follicle (LUF) syndrome (defined as failure to release any oocyte as determined by sonography) in gonadotropin-treated patients following human chorionic gonadotropin (hCG) versus the gonadotropin releasing hormone agonist (GnRH-a) leuprolide acetate. The present study was designed to determine if an ultra low dose gonadotropin regimen, designed not to raise the serum estradiol level much above normal for non-stimulated cycles, might result in a decrease in LUF following hCG treatment, and even reduce the rate to that seen following leuprolide acetate. The hypothesis tested was that the higher estradiol levels might suppress the pre-ovulatory follicle stimulating hormone (FSH) surge which, in turn, would inhibit plasmin production, thus preventing detachment of the oocyte from the follicle. The data did show a reduced rate of LUF incidence with either hCG or leuprolide acetate in ultra low-dose human menopausal gonadotropin (hMG-) treated patients compared to data from previous studies with conventional hMG/hCG therapy. Pregnancy rates were also similar following hCG or leuprolide acetate for release in low-dose hMG-treated patients. Preliminary data show that leuprolide acetate is superior to hCG for causing oocyte release when stimulation is with low-dose purified FSH, and possibly also that low-dose hMG is superior to low-dose purified FSH for producing superior pregnancy rates. PMID- 8213226 TI - Does gonadotropin suppression result in follicular development in premature ovarian failure? AB - It was hypothesized that premature ovarian failure is a self-perpetuating problem and that suppression of the endogenously raised gonadotropin levels may allow synchronization of follicular growth, so that when the suppression is removed, follicular development may be stimulated by the rapid rise in follicle stimulating hormone (FSH) levels. Microgynon (ethinylestradiol, 30 micrograms and levonorgestrel, 150 micrograms) was administered to eight women with premature ovarian failure for 12 weeks. Serum samples were collected weekly for radioimmunoassay of FSH, luteinizing hormone (LH), estradiol, progesterone and inhibin. On stopping Microgynon, ovarian ultrasonography was carried out, in addition to blood sampling, to monitor any follicular growth. Both FSH and LH levels declined to the normal follicular-phase range after 5 weeks of Microgynon treatment (mean +/- SD: FSH, 6.5 +/- 1.2 IU/l; LH, 8.9 +/- 1.6 IU/l). Both hormone levels rose rapidly after stopping treatment and were above the normal follicular-phase range by the 1st week. FSH reached pretreatment levels by 3 weeks, but LH did not reach the previously high levels until 7 weeks after stopping Microgynon administration. Estradiol and immunoreactive inhibin levels in serum were undetectable throughout the study. No follicular growth was seen on ultrasound scanning. Therefore, gonadotropin suppression in premature ovarian failure does not result in a resumption of follicular activity. PMID- 8213227 TI - Effect of dihydroergocryptine on serum prolactin levels and milk secretion in puerperal women. AB - The aim of the present study was to evaluate the efficacy and tolerability of the dopamine agonist drug dihydroergocryptine in the suppression of puerperal lactation. A single blind and placebo-controlled study was performed. A total of 90 postpartum women was acutely or repeatedly treated with dihydroergocryptine at different doses in order to investigate the efficacy of this drug in the suppression of puerperal lactation and to find the optimum dose for therapy. Prolactin levels, mammary symptomatology and rebound effects were monitored during the repeated treatment and also 1 and 8 days after drug discontinuation. With acute administration, dihydroergocryptine significantly reduced prolactin levels only at the dose of 10 mg and not at 5 mg. With repeated administration, a daily dose of 15 mg was more effective than 10 mg in reducing prolactin levels and in suppressing puerperal lactation. No side-effects occurred during the treatment. These results suggest that dihydroergocryptine might be considered an effective drug in the suppression of puerperal lactation. PMID- 8213228 TI - Endocrine and metabolic effects of guar gum in menopausal women. AB - The effect of a gel-forming dietary fiber, guar gum (15 g/day) on blood pressure, climacteric symptoms, serum hormones (estrone, estradiol, testosterone, androstenedione, follicle-stimulating hormone and luteinizing hormone) and on blood glucose and serum lipids (cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides) was studied in a double-blind, placebo-controlled, parallel-group trial involving 30 menopausal women. A total of 15 women (Group A) were treated with guar gum and 15 (Group B) with placebo, for 6 months. Patients visited the doctor at the beginning of the study and after 3 and 6 months of treatment. Climacteric symptoms decreased significantly (p < 0.001) in both groups. Serum total cholesterol decreased by 5% in the guar gum group but this was not statistically significant. No changes in serum hormone levels or in other lipid and blood glucose levels were observed in either group. Body weight and blood pressure also did not change. PMID- 8213229 TI - Effect of long-term spleen dialysate (Solcosplen) administration on plasma lipids and lipoproteins in early postmenopausal women. AB - A total of 46 early postmenopausal women with elevated levels of total cholesterol, triglycerides, low-density lipid (LDL) cholesterol and lowered high density lipoprotein cholesterol (HDL) cholesterol was treated with spleen dialysate (Solcosplen), 2 x 2 tablets daily for 6 months. Serum estradiol levels rose from 42.3 +/- 15.4 pg/ml to 60.6 +/- 23.6 pg/ml and the Kupperman Index decreased significantly after 6 months of treatment. Also, a significant decrease of total cholesterol, triglycerides, LDL cholesterol, and an increase of HDL cholesterol was observed. The changes showed no correlation with the estradiol concentration and no side-effects were evident. Solcosplen is recommended as a beneficial therapy for women in the early postmenopause. PMID- 8213230 TI - A uterine muscle contractile substance obtained from a human placental cDNA library. AB - A cDNA clone coding for an oxytocin-like substance was prepared from a human placental cDNA library using oxytocin antiserum. The cDNA size was approximately 900 bp. A mammalian expression vector containing the cDNA was constructed and transfected into Chinese hamster ovary (CHO) cells. The expression of immunoreactivity to oxytocin antiserum was observed by radioimmunoassay. The cultured medium of the transfected cells was assayed for uterine muscle contractile bioactivity using a Magnus apparatus. Bioactivity was eliminated by incubation with oxytocin antiserum. Thus, the cDNA clone, screened with oxytocin antibody, is surmised to code for an oxytocin-like activity, but the nucleotide and amino acid sequences responsible for the biological activity remain to be clarified. PMID- 8213231 TI - Cholinergic stimulation of progesterone and estradiol secretion by human granulosa cells cultured in serum-free medium. AB - Cholinergic effects on hormone secretion by human granulosa cells (GCs) are not well characterized. The aim of this study was to explore the direct action of acetylcholine and carbachol on progesterone and estradiol secretion of human GCs cultured in serum-free medium. Granulosa cells were obtained from 26 women undergoing in vitro fertilization and embryo transfer. Progesterone and estradiol production was measured in the presence and absence of acetylcholine, carbachol, or atropine using radioimmunoassays; statistical analysis of the data was performed by ANOVA. Acetylcholine significantly stimulated progesterone secretion by GCs in a dose-related manner. Estradiol secretion was also stimulated by acetylcholine, but this effect did not show dose dependency. Carbachol showed a similar stimulatory effect, but to a lower degree; both effects can be blocked by acetylcholine. The results suggest that cholinergic action on steroid production by human GCs is mediated through the muscarinic route, and cholinergic neurotransmission may have a physiological significance in the intra-ovarian regulatory pathways. PMID- 8213232 TI - Comparative effects of eel calcitonin, salmon calcitonin and [Asu1,7]eel calcitonin on hypophyseal and osteoblastic function. AB - Three different calcitonins: salmon calcitonin, eel calcitonin and the semi synthetic analog [Asu1,7]eel calcitonin have been evaluated for their ability to affect phosphoinositide hydrolysis in primary cultures of anterior pituitary cells and in the osteoblast-like UMR-106 cells. In both cellular systems a repeated treatment with any form of calcitonin induced an inhibition of inositol phospholipid turnover. Eel calcitonin and its analog were always more potent than salmon calcitonin, but the efficacy of the three polypeptides was comparable. In cultured anterior pituitary cells, the inhibitory effect on phosphoinositide hydrolysis observed after chronic treatment with calcitonin was accompanied by a reduction of prolactin release. In contrast, a single treatment of cultured anterior pituitary cells with eel calcitonin or its analog [Asu1,7]eel calcitonin induced an increase of inositol phosphate accumulation, while salmon calcitonin was inactive. Accordingly, eel and [Asu1,7]eel calcitonin, but not salmon calcitonin, induced a slight but significant stimulation of prolactin secretion. In UMR-106 cells, the three calcitonins exhibited similar potency and efficacy in reducing parathyroid hormone-stimulated 4 beta[3H]-phorbol-12,13-dibutyrate ([3H]PdBu) binding, an indirect index of protein kinase C activation. Taken together, these results suggest that, either at the pituitary or in osteoblast like cells, some of the effects exerted by calcitonin may be ascribed to an interference with the intracellular events initiated by modulation of phosphoinositide turnover. PMID- 8213233 TI - The round ligament: a target organ for steroid hormones. AB - Samples of the round ligament from pre- and post-menopausal women were analyzed immunohistochemically for estrogen and progesterone receptors. The steroid hormone receptors were localized in the smooth muscle cell nuclei, with stronger staining for progesterone receptors and somewhat weaker for estrogen receptors. Our findings support the view that the round ligament is a target organ influenced by hormones, which has implications for the changes in the ligament during pregnancy and pre- and postmenopausally. PMID- 8213234 TI - The effect of a comprehensive breast screening program on self-reported mammography use by primary care physicians and women in a health maintenance organization. AB - BACKGROUND: Mammography use is increasing in the United States, but most women older than 50 years still are not being screened regularly. A multicomponent program, with components for women and physicians, was conducted to increase screening among women aged 50 to 74 years in an independent practice association (IPA)-model health maintenance organization (HMO). METHODS: The participating women and physicians were surveyed in four waves to evaluate the program. We report on changes in mammography practices by both women and physicians between 1988 (preintervention year) and 1992 (postintervention year). Bivariate and multivariate analyses were calculated. RESULTS: The proportion of responding HMO physicians who recommended annual mammograms for women aged 50 to 74 years increased by 16 percent from 1988 to 1992 compared with an increase of 10 percent for control group physicians (nonsignificant). There was a 30 percent increase from 1988 to 1992 in the proportion of HMO women respondents who reported having had a mammogram in the past year compared with a 19 percent increase among control group women. The difference between these differences was highly significant. The intervention had the strongest effect on women with incomes of less than $30,000. CONCLUSIONS: A multicomponent program in an IPA-model HMO resulted in significant increases in the proportion of HMO women who had mammograms. Similar approaches should be tested in other settings. PMID- 8213235 TI - Oxygen saturation in children living at moderate altitude. AB - BACKGROUND: Physicians caring for newborns and infants residing at or traveling to moderate altitude have little information available about the normal range for arterial oxygen saturation (SaO2) measured by pulse oximetry. To aid clinicians in making rational decisions about the oxygen status of children at moderate altitude, we measured SaO2 in newborns and infants who came to two family practice offices located at an altitude of 2800 meters (9000 feet) to obtain normal values for both well-child and illness visits. METHODS: SaO2 measured by pulse oximetry was recorded for children younger than 2 years seen consecutively in a family practice clinic for care for any reason. The children all resided at an altitude of 2800 m (9000 ft). RESULTS: The mean SaO2 for healthy awake infants was 91.7 percent, significantly lower than the reported normal ranges for either sea level or Denver. Saturation levels in infants with minor acute illnesses did not differ from saturation levels in healthy infants, while infants with lower respiratory tract infections had significantly lower SaO2 measurements. CONCLUSIONS: SaO2 levels are significantly lower in newborns and infants living at moderate altitude. Measurement of SaO2 at moderate altitude can be helpful in the care of both healthy and ill newborns or infants. PMID- 8213236 TI - Recognition and management of obesity in a family practice setting. AB - BACKGROUND: Research on the diagnosis and management of obesity in primary care is limited. Our study goals were to describe the rate of obesity in a primary care setting, to identify factors associated with clinically recognized obesity, and to ascertain the level of diet and exercise counseling for obesity. METHODS: Medical records from a private group practice were used for a historical cohort study of 276 patients (aged 40 years and older) who were provided care for a maximum 4.5-year follow-up period. RESULTS: Forty-six percent of the study patients (95 percent confidence interval = 0.43, 0.49) received an obesity diagnosis according to medical record notations. The diagnosis of obesity, in turn, was predicted by body mass index (BMI) quartile (P < 0.001) and a positive family history of cardiovascular disease (P < 0.01). Those patients with a diagnosis of obesity had a higher mean level of subsequent weight and diet counseling (P = 0.0001) but the same level (P = 0.11) of exercise counseling as nonobese patients. Weight and diet counseling was also predicted by diabetes (P = 0.0001) and hypercholesterolemia (P = 0.0003). CONCLUSIONS: The clinical recognition of obesity was not determined by BMI alone. Although weight and diet counseling was initiated for those individuals described as obese, there was a relatively low level of exercise counseling among these patients. Additional research could provide ways of reducing both physician and patient barriers to exercise counseling. PMID- 8213237 TI - The prevalence rate of sexual trauma in a primary care clinic. AB - BACKGROUND: Despite the high prevalence rate of sexual victimization in the general population, little is known about the characteristics of abuse victims in primary care. We studied the prevalence rate of childhood and adult sexual trauma in a primary care clinic, associated psychological distress, and patients' attitudes about physician inquiry into past sexual victimization. METHODS: Self report questionnaires were given to 162 women in a primary care clinic inquiring about past episodes of childhood sexual abuse, adult sexual assault, and patients' desire that their physicians be aware of their sexually traumatic experiences. The women also completed the Trauma Symptom Checklist-40 (TSC-40), a measure of psychological distress. RESULTS: The rates of childhood sexual abuse (37 percent) and adult sexual assault (29 percent) in this primary care clinic were comparable with, but somewhat above, the rates reported for the general population. Although most of the women (61 percent) believed it was appropriate for their physician to ask about previous victimization, only 4 percent had been asked. Women who had experienced sexual trauma were more distressed when compared with nonvictimized women, as measured by the TSC-40. Childhood sexual abuse was associated with greater distress than was adult sexual assault, and combinations of childhood and adult trauma were associated with the highest distress levels. CONCLUSIONS: A history of sexual abuse or assault can be a relatively common finding in primary care clinics. Patients might benefit from routine physician inquiry into histories of childhood and adult sexual victimization, and physicians should be mindful of the long-term medical and psychological sequelae that frequently result from this trauma. PMID- 8213238 TI - Elderly outpatients respond favorably to a physician-initiated advance directive discussion. AB - BACKGROUND: Little is known about the emotional impact of physician-initiated advance directive discussions. METHODS: One hundred ambulatory patients aged 65 years and older were randomly assigned to receive either a physician-initiated discussion of advance directive choices of a discussion of health promotion issues. Prediscussion, immediate postdiscussion, and 1-week postdiscussion measures of positive and negative affect were measured for both groups. RESULTS: Neither discussion topic resulted in adverse emotional or attitudinal responses. Only the advance directive participants showed positive affective and attitudinal responses to the discussion, including an increase in positive affect, an increased sense of physician-patient understanding, and increased thought and discussion about life-support issues in the week following the discussion. For those participants receiving the advance directive discussion, longer physician patient relationships and higher educational levels significantly predicted a more positive affective response. Lower scores on indices of mental and physical health and a stronger belief that physicians should discuss advance directive issues significantly predicted a more negative affective response to the advance directive discussion. CONCLUSIONS: Physicians should anticipate positive emotional responses when they initiate advance directive discussions with their elderly outpatients. Advance directive discussions will be received most positively by patients who enjoy good psychological and physical health and when initiated in the context of an established physician-patient relationship. PMID- 8213239 TI - Preventing hepatitis B: focus on women and their families. AB - BACKGROUND: Infections contracted during infancy or childhood are responsible for 42 percent of case of chronic hepatitis B disease, and in 25 percent or more these infections result in death from hepatoma or cirrhosis during adulthood. Hepatitis B vaccine and immune globulin provide the means of preventing the disease and its sequelae, but their proper use requires clinical strategies for deciding which patients are at risk and which responses are appropriate for family practice. METHODS: A MEDLINE search of the literature pertaining to hepatitis B and its prevention, a review from the Centers for Disease Control (CDC), and critique by both practitioners and members of the CDC Hepatitis Branch led to the development of the clinical guidelines reported in this review. RESULTS AND CONCLUSIONS: Women at high risk for hepatitis B should be screened, including during pregnancy, by testing for hepatitis B core antibody. Those at low risk should be screened by testing for hepatitis B surface antigen. Susceptible high-risk women should be vaccinated; pregnancy is not a contraindication. Administration of hepatitis B immune globulin and vaccine to newborns is 95 percent effective in preventing transmission from a hepatitis B infected mother. Follow-up vaccination is critical. Prophylaxis of contacts can include hepatitis B immune globulin and vaccination with or without previous testing, depending on age group and risk. Testing for hepatitis B surface antibody to assess development of immunity after vaccination is indicated only for those with ongoing exposure. PMID- 8213240 TI - Screening for adolescent idiopathic scoliosis: a report from the United States Preventive Services Task Force. AB - The analysis of screening for adolescent idiopathic scoliosis published by the USPSTF is an important document, both because it reintroduces the task force as an important player in the clinical policies business and because it points (once again) to the deficiencies in our scientific understanding of a relatively common condition. Certainly medicolegal, cost, outcome, and patient preference issues not completely accounted for in the task force analysis need to be included in a fully developed clinical policy for this condition. The findings allow family physicians to use their own judgment pending publication of better and more complete data. On the whole the USPSTF analysis suggests that a nonaggressive approach toward screening is indicated until we have evidence clearly pointing one direction or the other. PMID- 8213241 TI - Prolonged delirium tremens requiring massive doses of medication. AB - Delirium tremens might last for weeks and treatment requires massive benzodiazepine doses, yet it is possible to manage patients with this condition successfully. In this case of delirium tremens, standard agents at the usual recommended doses were not sufficient to achieve control of confusion and agitation or to stabilize neurologic and cardiovascular parameters. The patient required extraordinarily high doses of central nervous system depressants for an extended period. Midazolam, a short-acting benzodiazepine, was used but was associated with metabolic acidosis and was extremely expensive. Although high dose midazolam should probably be avoided, extremely high dose benzodiazepine use for an extended period might be necessary in some cases. In this circumstance we advise diazepam because of its low cost and relative safety. The tendencies to withhold large doses for fear of side effects or to give up in cases requiring prolonged intensive support must be resisted to minimize the mortality from this severe illness. PMID- 8213242 TI - Cesarean section scar endometriosis. PMID- 8213243 TI - Obsessive-compulsive disorder in childhood: a behavioral approach to management. PMID- 8213244 TI - Recognition of sexual abuse. PMID- 8213245 TI - Breast cancer care: a beacon of change? PMID- 8213246 TI - Nicholas J. Pisacano, MD, Memorial Foundation. PMID- 8213248 TI - Obstetrics in family practice. PMID- 8213247 TI - Exercise stress test training. PMID- 8213249 TI - Transvaginal ultrasound and surveillance on estrogen therapy. PMID- 8213250 TI - Detection and measurement of vitamins K1 and K2 in human cortical and trabecular bone. AB - Vitamin K plays an essential role in the gamma carboxylation of the gla containing proteins of bone matrix, such as osteocalcin. We have measured the concentration of vitamin K1 (VK) and of the menaquinones MK-6, MK-7, and MK-8, the three major vitamin K2 moieties, in trabecular and cortical bone taken from the femoral neck of patients undergoing hip replacement. Both bone compartments were found to contain large amounts of VK, MK-6, MK-7, and MK-8. Concentrations were as high as those reported for the liver, the major storage organ for vitamin K. Further research is required to examine the association between vitamin K in bone and the gamma carboxylation of vitamin K-dependent bone proteins. PMID- 8213251 TI - Biologic activity of dihydroxylated 19-nor-(pre)vitamin D3. AB - Vitamin D3 and its hydroxylated metabolites are normally in thermal equilibrium with their previtamin D isomers. To evaluate the biologic activity of 1 alpha, 25 dihydroxyprevitamin D3, we synthesized 19-nor analogs of 1 alpha, 25 dihydroxy(pre)vitamin D3 because the absence of a C19 methylene group prevents the isomerization of these analogs. The affinity of 1 alpha, 25-(OH)2D3-19-nor-D3 for the intestinal vitamin D receptor and plasma vitamin D binding protein was mildly decreased [30 and 20% of the affinity of 1 alpha, 25-(OH)2D3, respectively], but the affinity of 1 alpha, 25-(OH)2-19-nor-previtamin D3 was only 1 and 6% of that of 1 alpha, 25-(OH)2D3 for the receptor and DBP, respectively. The in vitro effects on human promyeloid leukemia (HL-60 cell) differentiation and osteocalcin secretion by human osteosarcoma (MG-63) cells by 1 alpha, 25-(OH)2-19-nor-D3 were nearly identical to those of 1 alpha-25-(OH)2D3, whereas 19-nor-previtamin D3 showed poor activity (2%). The in vivo calcemic effects of both analogs, studied in vitamin D-deficient chicks treated for 10 consecutive days with the analogs, showed no activity of the previtamin D3 analog and reduced calcemic effects (< or = 10%) of 1 alpha, 25-(OH)2-19-nor-D3. We conclude that the previtamin D form of 1 alpha, 25-(OH)2D3 has lost most of its biologic activity in vitro and in vivo. PMID- 8213252 TI - Reproductive correlates of bone mass in elderly women. Study of Osteoporotic Fractures Research Group. AB - Results from previous studies of reproductive factors and bone density have been conflicting; some demonstrate a beneficial effect, but others show a detrimental effect on bone density. The present study investigates the association of parity, lactation, and menstruation with radial bone density in 2230 white women, 65 years of age and older. Bone density was assessed by single-photon absorptiometry. Linear multiple regression was utilized to determine if reproductive factors were associated with radial bone density. The number of births, duration of menstrual bleeding, age at menarche, and years menstruating were significant independent predictors of postmenopausal bone density of the radius. A 1.4% increase in distal radius bone density was observed with each additional birth. Women who began menstruation at age 9 had 6.3% higher bone density than women who began at age 16. Women who menstruated for 3 days during each menstrual cycle had 2.8% less distal radius bone density than women who bled for 7 days. Each decade of menstruation was associated with a 2% greater distal radius bone density. No difference in bone density was demonstrated for women who breast-fed and women who did not. Length of the menstrual cycle, amount of menstrual flow, and irregularity of the menstrual cycle were not significantly associated with radial bone mineral density. In conclusion, pregnancy and menstruation are associated with postmenopausal bone density of the radius. PMID- 8213253 TI - Effect of age and osteoarthritis on bone mineral in rhesus monkey vertebrae. AB - We have used vertebrae of free-ranging rhesus macaques to study the effect of age and osteoarthritis on bone mineralization and bone density and to relate these findings to weight, sex, parity, and mineral chemistry. Bone mineralization was determined using the density fractionation technique and bone density using dual photon absorptiometry. Arthritis was determined osteologically. We found a relationship between mineralization, age, and osteophytes, such that mineralization rose with age in nonarthritics and decreased with age in arthritics. This could also be seen when the females were examined separately. In males, only an increase in mineralization with age could be seen. In females mineralization decreases with parity. Also in females, DPA density decreases with age and increases with parity. No relationships with DPA density could be seen using males and females together or males alone. In conclusion, we have shown that normal skeletal aging in rhesus monkeys is accompanied by an increase in mineralization similar to that in other species, but this is not true in the presence of osteoarthritis. In the females parity has an important effect because it seems to build up bone mass even though the bone present may be undermineralized. PMID- 8213254 TI - Effect of basic fibroblast growth factor on the growth and differentiation of adult stromal bone marrow cells: enhanced development of mineralized bone-like tissue in culture. AB - Rat stromal bone marrow cells (SBMC) were shown to produce mineralized bone-like tissue in culture in the presence of dexamethasone, ascorbic acid, and beta glycerophosphate. The addition of 3 ng/ml of basic fibroblast growth factor (bFGF) resulted in a significant increase in formation of mineralized tissue. The present study was aimed at assessing the effect of bFGF on the proliferation and differentiation of SBMC and on the sequential development of mineralized bone like tissue in culture. Transmission electron microscopy of bFGF-treated cultures demonstrated the development of a multilayered structure resembling mineralized bone tissue consisting of cell layers embedded within a heavy extracellular matrix. The matrix was rich in bundles of collagen fibers associated with extensive mineral deposits consisting of hydroxyapatite as determined by infrared spectrophotometry. The addition of 3 ng/ml of bFGF resulted in significant enhancement of [3H]thymidine and [3H]proline incorporation and protein accumulation by 12-, 2.5-, and 2.5-fold, respectively. bFGF treatment increased cAMP responsiveness, alkaline phosphatase activity, osteocalcin level, 45Ca2+ deposition, and mineralized-like tissue formation and induced the earlier expression of these markers in the treated culture. A biphasic sequence of events was observed during the development of mineralized bone-like tissue in bFGF treated and control cultures. The first phase is characterized by cell proliferation and matrix accumulation and is reflected by a progressive increase in [3H]thymidine and [3H]proline incorporation until day 11. The second phase, which follows, is characterized by a sharp decline in cell proliferation and matrix accumulation and a concomitant expression of osteoblast differentiation as reflected by the progressive increase in alkaline phosphatase activity, mineral deposition, and osteocalcin expression. Treatment of cultures with bFGF accentuated this biphasic sequence of events. These results indicate that bFGF has the capacity to stimulate both the growth and the biochemical functions of SBMC obtained from a young adult animal. PMID- 8213255 TI - Effects of aerobic training on bone mineral density of postmenopausal women. AB - A total of 76 women were enrolled and 55 naturally postmenopausal women completed a 12 month study investigating the effects of aerobic training plus calcium supplementation on lumbar (L2-4) bone mineral density (BMD) and forearm BMD. Training was conducted on treadmills at 70-85% of maximal heart rate for 30 or 45 minutes, three times per week for 12 months. Lumbar BMD was measured with dual photon absorptiometry and forearm BMD with single-photon absorptiometry. Groups were similar with respect to age, weight, months since menopause, height, maximal oxygen uptake (VO2max), and lumbar and forearm BMD upon entering the study. Following training, percentage changes in VO2max were significantly different between the control and exercise groups but not between exercise groups. ANOVA evaluating lumbar BMD revealed a nonsignificant interaction effect and no significant changes (p > 0.05) between groups or times. The control (N = 19), 30 minute (N = 20), and 45 minute (N = 16) groups percentage lumbar BMD changes (X +/- SD) over 12 months were -0.61 +/- 3.40, -0.48 +/- 3.63, and 0.81 +/- 4.53%, respectively. The 95% confidence limits for percentage changes in lumbar BMD for the control, 30 minute, and 45 minute groups were -2.25 to 1.02, -2.18 to 1.22, and -1.16 to 3.22%, respectively. Forearm BMD changes were also not significant. Improvement in lumbar BMD was weakly but positively correlated with improvements in VO2max, r = 0.28, p < 0.05. Women < or = 6 years of the onset of menopause had an accelerated lumbar BMD loss compared to subjects who were > 6 years postmenopausal, and this subset's BMD changes were examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213256 TI - Effects of endurance exercise on bone mass and mechanical properties in intact and ovariectomized rats. AB - Exercise may play a role in the prevention of bone fractures in postmenopausal osteoporosis. The effects of endurance exercise on bone properties were assessed in 9-month-old sham-operated (SH) and ovariectomized (OVX) rats. The rats were either kept sedentary (SED) or were exercised (EX) on a rodent treadmill at 21 m/minute, 7% grade, 40 minutes/day, 4 days/week for 3 months. Bone mineral (by ash weight), morphometry, and biomechanical properties (by three-point bending) were evaluated after excision of bones at sacrifice. Ovariectomy resulted in a loss of bone mineral in femur, tibia, and fourth lumbar vertebra (L4), but biomechanical (force, deformation, stress, strain, and modulus of elasticity) and morphometric (length, cortical and medullary area, and moment of inertia) properties of femur were maintained. The ash weight of femur and tibia, but not L4, as well as femur yield and maximum force and moment of inertia, were improved in OVX-EX rats compared to OVX-SED animals. In SH rats exercise had no influence on ash weight of any of the three bones or femur morphometric properties, yet femur maximum force and plastic deformation were significantly enhanced compared to SH-SED rats. The results of the present study suggest that endurance exercise has beneficial effects on the bone mineral as well as biomechanical properties (femur yield and maximum force) during early stages after ovariectomy and improves the bending strength of the intact femur without an effect on bone mineral in sham-operated rats. PMID- 8213257 TI - Endothelin-1 modulates calcium signaling by epidermal growth factor, alpha thrombin, and prostaglandin E1 in UMR-106 osteoblastic cells. AB - Local factors play an important role in the regulation of bone metabolism. The homologous and heterologous desensitization of responses to these factors may be crucial in the modulation of bone cell signaling. In this study, the effects and interactions of endothelin-1 (25 nM), alpha-thrombin (0.9 microM), epidermal growth factor (40 nM), prostaglandin E1 (5 microM), and prostaglandin F1 alpha (5 microM) were examined on calcium signaling in UMR-106 rat osteoblastic osteosarcoma cells. Intracellular calcium was measured using fluo-3 fluorescent dye. All agents elicited calcium transients at these concentrations and showed homologous desensitization to their repeated administration. Preincubation for 60 minutes with 500 microM monodansylcadaverine and 30 minutes or 24 h preincubation with 0.5 microM indomethacin did not affect homologous desensitization, suggesting that neither the internalization of receptors nor prostaglandins are involved in this event. Pretreatment for 3 minutes with 2 microM 4 beta-phorbol 12 beta, 13 alpha-dibutyrate significantly reduced the calcium elevations elicited by the first application of these compounds, whereas an inactive phorbol, 12,13-didecanoate, had no effect. Pretreatment for 4 minutes with 0.5 microM forskolin decreased the calcium signal response to PGE1 only. Pretreatment with endothelin-1 for 3 minutes significantly decreased the calcium signals elicited by epidermal growth factor and alpha-thrombin. Prior administration of endothelin-1 significantly increased prostaglandin E1-stimulated calcium transients, whereas prostaglandin F1 alpha responses were not affected. Preincubation with indomethacin did not alter any of the interactions. Responses to endothelin-1 were not significantly altered by 2-3 minutes pretreatment with the other factors, nor was there cross-desensitization among the other factors. The results could indicate that endothelin-1 has a unique and specific role in the modulation of bone cell signaling. PMID- 8213258 TI - Linkage of extracellular and intracellular control of cytosolic Ca2+ in rat osteoclasts in the presence of thapsigargin. AB - Cytosolic [Ca2+] was measured in single osteoclasts using fura-2 in experiments investigating the effects of Ca2+ "receptor" activation using thapsigargin as a means of depleting intracellular Ca2+ stores. Application of 4 microM thapsigargin to osteoclasts in Ca(2+)-free solutions resulted in an elevation of cytosolic [Ca2+]. Under similar conditions, activation of the osteoclast Ca2+ receptor by the substitute divalent cation agonist, Ni2+, resulted in a transient elevation of cytosolic [Ca2+]. In both instances, restoration of extracellular [Ca2+] to 1.25 mM resulted in an "overshoot" of cytosolic [Ca2+]. Prior depletion of intracellular Ca2+ stores by thapsigargin markedly reduced the magnitude of the cytosolic [Ca2+] response to a subsequent application of 5 mM Ni2+. The application of 2 microM thapsigargin to intercept the falling phase of the Ni(2+) induced cytosolic Ca2+ signal resulted in a sustained elevation of cytosolic [Ca2+], which was terminated by a second application of the same Ni2+. Furthermore, the sustained elevation of cytosolic [Ca2+] induced by thapsigargin application alone was abolished by late application of Ni2+. We conclude that activation of the surface membrane Ca2+ receptor on the osteoclast results in the cytosolic release of Ca2+ from intracellular storage organelles; the refilling of such stores depends upon a thapsigargin-sensitive Ca(2+)-ATPase; store depletion induces capacitative Ca2+ influx; and the Ca2+ influx pathway is sensitive to blockade by Ni2+. PMID- 8213259 TI - Role of the negative glucocorticoid regulatory element in glucocorticoid repression of the human osteocalcin promoter. AB - In osteoblast-like cells in culture, the human osteocalcin gene promoter basal activity is repressed by glucocorticoids, reflecting the repression of serum osteocalcin concentrations noted in syndromes of glucocorticoid excess. 1,25 Dihydroxyvitamin D3 [1,25-(OH)2D3], the active hormonal form of vitamin D, induces the osteocalcin promoter through a vitamin D response element (VDRE), and glucocorticoids also repress the vitamin D-induced promoter. This study addresses the role of a glucocorticoid receptor (GR) binding site overlapping the TATA box of the osteocalcin promoter, which had been proposed as a negative glucocorticoid response element (nGRE), invoking a steric interference mechanism of glucocorticoid repression. Confirmation of the role of the nGRE in regulating basal activity was obtained using promoter constructs containing a TATA box swap. However, a minor component of repression of 1,25-(OH)2D3 induced activity remained in the absence of the nGRE. In addition, glucocorticoid repression of the human osteocalcin promotor was shown to be cell line specific. This result is not compatible with a simple model of repression and suggests the existence of unidentified cell-specific factors that are involved in the repression event. Repression of the osteocalcin promoter was compatible with a composite model involving both the nGRE site and glucocorticoid regulation of factors that bind the vitamin D response element. PMID- 8213260 TI - Electric fields modulate bone cell function in a density-dependent manner. AB - The influence of an extremely low frequency (ELF) electric field stimulus (30 Hz at 6 microV/cm rms), known to promote bone formation in vivo, was evaluated for its ability to affect bone cell function in vitro. To accomplish this, we developed an apparatus for the exposure of monolayer cell systems to electric fields in a manner that provides relatively uniform electric field exposure of multiple cell samples as well as a rigorous sham exposure. We show that field exposure significantly limits the normal increase in osteoblastic cell number and enhances alkaline phosphatase activity compared to sham-exposed samples. Moreover, these alterations are shown to occur in a cell density-dependent manner. Samples plated at 6 x 10(3) cells/cm2 show no effect of field exposure. In samples plated at 30 x 10(3) cells/cm2, 72 h of field exposure resulted in 25% fewer cells in the exposed samples, and a doubling of alkaline phosphatase activity in those cells compared to sham exposure. Experiments using a 12 h exposure to preclude significant changes in cell number during the exposure show this density-dependent response to be biphasic. Sparse cultures (< 50 x 10(3) cells/cm2) were not found to be affected by the field exposure, but increases in alkaline phosphatase activity occurred in cultures at densities of 50-200 x 10(3) and 200-350 x 10(3) cells/cm2 and no effect on alkaline phosphatase activity was seen in confluent cell cultures of greater than 350 x 10(3) cells/cm2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213262 TI - Tumor necrosis factor alpha decreases 1,25-dihydroxyvitamin D3 receptors in osteoblastic ROS 17/2.8 cells. AB - Bone remodeling is a complex process regulated by systemic hormones, local cytokines, and growth factors. One cytokine, tumor necrosis factor alpha (TNF alpha), is known to have potent inhibitory effects on osteoblast matrix protein production and to stimulate osteoclast recruitment. We have previously shown that TNF-alpha inhibits 1,25-(OH)2D3-stimulated synthesis of bone gla protein (BGP), an abundant and osteoblast-specific matrix constituent. We hypothesized that the mechanism of TNF-alpha action included inhibition of intracellular 1,25-(OH)2D3 receptor (VDR) number or function. To test this, the osteoblastic cell line ROS 17/2.8 was cultured in the presence or absence of TNF-alpha (100 ng/ml), and binding of [3H]1,25-(OH)2D3 to 0.3 M KCl extracts of cytosol was measured by equilibrium assay. Specific [3H]1,25-(OH)2D3 binding decreased 70%, 25 h after addition of TNF-alpha. The decrease in [3H]1,25-(OH)2D3 binding was seen by 18 h, was sustained throughout the 72 h culture period, and was greater in low-density cultures. Scatchard analysis confirmed that TNF-alpha (100 ng/ml for 24 h) caused a decrease in the number of binding sites without change in VDR affinity. Northern analysis with a VDR riboprobe revealed that the decrease in VDR occurred without a change in the 4.4 kb steady-state VDR mRNA [VDR/cyclophilin mRNA signal ratio: control, 2.25; TNF-alpha, 2.24 (24 h), 2.17 (40 h), n = 2 flasks/time point]. These results suggest that TNF-alpha action on osteoblastic cells includes an inhibitory effect on VDR number at a point distal to the synthesis of VDR mRNA. PMID- 8213261 TI - Purification and fragmentation of nondenatured bone sialoprotein: evidence for a cryptic, RGD-resistant cell attachment domain. AB - Bone sialoprotein (BSP), a small (approximately 80,000 M(r)) integrin binding, RGD-containing bone matrix glycoprotein, has been purified in milligram quantities from the serum-free medium of the rat osteosarcoma cell line UMR-106 BSP using nondenaturing conditions. Routine protein purification without serine protease inhibitors or reducing agents consistently resulted in three major fragments. The largest fragment (E1) started at amino acid 117 and did not bind to antibodies made to the RGD region of the protein. Furthermore, the smallest fragment (E3), was shown by sequencing to contain the RGD region of the protein. Digestion of intact BSP with highly purified chymotrypsin also resulted in a large fragment (C1) with properties nearly identical to those of E1. The large, non-RGD-containing fragments, E1 and C1, as well as the intact BSP, supported attachment by normal human bone cells and human skin fibroblasts in vitro. Attachment to the intact BSP was totally blocked by 0.4 mM GRGDS peptide. Both preparations of skin fibroblasts and approximately half of the preparations of normal human bone cells, however, also would not attach to the E1 and C1 fragments in the presence of 0.4 mM GRGDS peptide. In contrast, half of the bone cell preparations had significant attachment activity to E1 (> 50%) and C1 (> 25%) in the presence of 0.4 mM GRGDS peptide. These data suggest that cleavage of the BSP results in either (1) the exposure of a previously unavailable or cryptic cell attachment site or (2) a conformational change that increases the affinity of the complex between a non-RGD-encoded binding region of the E1 and C1 fragments and at least one receptor. The possible homology of the second, non-RGD suppressible site of BSP with the second cell attachment site on the gamma chain of fibrinogen is discussed. PMID- 8213263 TI - Retention and relearning of spatial delayed alternation in rats after combined or sequential lesions of the prefrontal and parietal cortex. AB - Lesions of the medial prefrontal cortex strongly impaired rats' delayed alternation behaviour in a T-maze, both when the lesion was inflicted after the initial acquisition of the task and when the lesion was added after criterion performance had been reattained following an ablation of the parietal cortex. Lesions of the parietal cortex did not impair this behaviour, either when the parietal lesion was inflicted after the initial acquisition of the task or when it was added to a prefrontal lesion after criterion performance had been reattained. Combined, one stage, parietal and prefrontal lesions did not have stronger effect on delayed alternation than did prefrontal lesions alone. These results indicate that in spite of the strong anatomical connectivity between the prefrontal and parietal "association" cortex the latter is not necessary for the recovery of delayed alternation after prefrontal lesions. In comparison with the parietal cortex, the prefrontal cortex seems to be uniquely involved in mediation of delayed alternation. PMID- 8213264 TI - The relative roles of vertices and sides in determining perceptual centres within shapes. AB - In the main experiment, subjects estimated the centre of five polygons in three variants: whole contour, only sides, or only corners. The perceived centre was closer to the area barycentre than to any other mathematical centre. Errors decreased as the number of sides of the figures increased. Larger mean deviations and variability were observed for the corner-only variant. Errors did not differ between the other two variants. However, this could be due to the fact that in the side-only variant only a small portion of the sides was erased, making in this way this variant to be similar to the complete contour. To exclude this possibility, in a Control Experiment side-only figures with different lengths erased around the corners were used. Since there was no worsening of the performance with longer erasings, it is concluded that, in finding the centre, the visual system relies mainly on the information provided by the sides, while a role of the corners is not evident. PMID- 8213265 TI - Model of visual localization. AB - The position of an object in the visual field is a global characteristic of the object which must be determined shortly after its appearance. This characteristic is useful for organizing actions towards the object or for its better examination. A model of visual localization based on the concept of "image function" is proposed. It predicts that the centroid of a visual object determines its position. The centroid could be easily extracted from the maximum in the image function under certain conditions. Symmetry and size may influence the accuracy (absolute and relative) in locating visual objects. PMID- 8213266 TI - Phototactic choice between two lights of various intensity in flies. AB - Under the conditions of double choice in a Y-maze, proportion of flies gathering in its arm depended on its relative illumination, approximately so that (1) at, or below the lower critical relative intensity limit, it assumed a constant minimum value; (2) at, or above the species-specific upper critical limit, the proportion of choice assumed a constant maximum value; whereas (3) between these illumination limits it roughly depended linearly on the logarithm of relative intensity of the light. (However, variations of behavioural responsiveness of flies towards white lights with different intensities, underlying their choice in the maze, suggest that the dependence of proportion of choice on relative light intensity has presumably not a zigzag but a sigmoid-shape course). The slope of the graph of linear proportionality of choice to the logarithm of light intensity differed in the housefly and the blowflies, similarly as did the extreme values of the proportion of choice beyond the critical intensity limits. The proportion of choice depended on a type of the maze (being different in a Y- and a T-maze), but not on its size, and it did not depend either on adaptation of flies to light or darkness prior to the experiment, or on the age of flies. PMID- 8213267 TI - Factors influencing the responses to nest damage in the African weaver ant. Oecophylla longinoda (Latreille). AB - Responses of the African weaver ants (Oecophylla longinoda) to nest damages were studied in the field in Nigeria. During the wet season, the ants responded to nest damages almost unexceptionnally by a quick onset of nest-repairing behaviour. The latencies to the start of nest-repairing activities (LN) did not depend on the size of the damage, but they were significantly shorter during the night, and positively correlated with ambient temperature. During the dry season, the ants responded to large nest damages mainly by abandonning the nest. In the case of medium size damages, the onset of nest-repairing behaviour was equally rapid as during the wet season, but in the case of small damages it was sometimes greatly delayed (up to three hours). The values of LN did not differ between the nighttime and the remaining times of the day, and they were not correlated with ambient temperature. PMID- 8213268 TI - Influence of the intertectal connection upon visual responses in the cat's superior colliculus. AB - Visual responses of single units in the superficial layers of the superior colliculus were examined in cats with pretrigeminal brainstem transections and lesions in the contralateral superior colliculus. The percentage of direction selective cells was decreased in lesioned as compared to non-lesioned cats. This effect may be a result of the elimination of suppression from the contralateral superior colliculus as well as disturbance of the projections from other structures of the contralateral hemisphere. PMID- 8213269 TI - The influence of vibrissae removal on copulatory behaviour in male rats. AB - The influence of vibrissae removal on copulatory behaviour was tested in both sexually naive and experienced male rats. The experiment consisted of 3 experimental and 3 control sessions. In some sexually naive rats, the removal of the vibrissae caused absence of copulatory behaviour during the first or all 3 experimental sessions, while in other ones this procedure remained without any apparent influence on copulatory behaviour. Three weeks later, after vibrissae have regrown, all of these rats displayed the copulatory behaviour. However, after the regrowth of the vibrissae, in rats with previously impaired copulatory behaviour a shortening of postejaculatory intervals was observed, while in rats with unaffected copulatory behaviour no such differences were observed. In contrast to observations in the sexually naive rats, in the sexually experienced ones removal of vibrissae led to the activation of copulatory behaviour, manifested by shortening of ejaculation latencies and mean interintromission intervals and an increase in hit rate. PMID- 8213270 TI - Horseradish peroxidase localization of the mylohyoid motoneurones in the rabbit. AB - Experiments were performed with anaesthetized (urethan and chloralose) spontaneously breathing rabbits. Horseradish peroxidase (HRP) was injected (1 mg) with a Hamilton syringe into the end of the sectioned mylohyoid nerve. The HRP labelled neurones could be localized in the motor nucleus of the trigeminal nerve (N.V.mt.). It was found that the labelled neurones are present in the caudal and intermediate part of the nucleus. However, their largest agglomerations were noted in the caudal part, where they occupied the entire frontal section of the nucleus. It is assumed that the N.V.mt. directing their axons to the muscles of the upper respiratory airways, simultaneously send collaterals to the central respiratory neurones participating in the regulation of the respiratory rhythm. According to this hypothesis the neurones of the N.V.mt. may ensure synchronisation between the upper and lower respiratory system. PMID- 8213271 TI - Cortical projections of the thalamic mediodorsal nucleus in the rat. Definition of the prefrontal cortex. AB - Deposits of somatopetal tracers, that filled the entire dorsolateral cortex of one hemisphere, labelled only a few cell bodies in the thalamic mediodorsal nucleus (MD). Further experiments served to confirm the existence of strong projections from MD to the mesial and suprarhinal areas of the frontal cortex. Thus, only a very small proportion of the MD neurones in the rat projects outside the cortical areas described first by Leonard (1969). We conclude that at least in the rat, cortical projections of the MD are selective enough to be used as the basis for definition of the prefrontal cortex. PMID- 8213272 TI - Prognostic parameters in benign astrocytomas. AB - To elucidate the prognosis of different types of benign astrocytomas and to ascertain whether patients with partially resected benign astrocytomas, or any subtype of these, would benefit from postoperative radiotherapy, we studied retrospectively material comprising 300 patients with benign astrocytomas treated in the period 1956 to 1991. The pilocytic type of astrocytoma was found to have an outstandingly good prognosis and should be regarded as a distinct nosological entity. For the non-pilocytic supratentorial astrocytomas, a multivariate regression analysis showed that age, tumour site, Kernohan grade and lymphocytic perivascular cuffing influenced survival. The proportion of gemistocytes increased with age. After correction for age, the proportion of gemistocytes had no significant influence on survival. It was not possible to demonstrate any influence of radiotherapy on median survival time of patients with non-pilocytic supratentorial benign astrocytomas. The study emphasizes the necessity of a prospective combined multicenter analysis of the effect of radiation on benign astrocytomas. PMID- 8213273 TI - Intracranial tumours in the first year of life. A report on 51 cases. AB - The authors report on 51 infants with intracranial tumours treated in an eleven year period; these infants represent 13% of the total population of children with intracranial tumours who have been operated on in the same institution during the same period of time. Males (28 cases) were slightly more frequent. Astrocytomas (17 cases), medulloblastomas (12 cases), and ependymal tumours (5 cases) were the commonest histologic types. Signs and symptoms of increased intracranial pressure were by far the most frequent clinical manifestations, followed by seizure disorders. Thirty tumours were localized within the supratentorial, and 21 within the subtentorial compartment. The parasellar region (10 cases) and the lateral cerebral ventricles (8 cases) for the supratentorial tumours, the inferior cerebellar vermis and fourth ventricle (13 cases) for the infratentorial tumours appeared to be the preferred topographic locations. Craniotomies were carried out in 44 infants, with a total or radical removal of the tumour in 19 cases, a subtotal removal in 6 cases, and a partial removal in 17 cases. In 3 cases only a biopsy procedure was performed. Twenty-nine of these patients required an ancillary procedure such as CSF shunting. Three subjects underwent a biopsy procedure and 1 infant the insertion of a CSF shunting device only. Surgery was not performed in 5 cases. Overall, there were two surgical deaths. Two infants died before any surgical treatment could be performed. Radiation therapy was administered to 9 patients when they had reached three years of age. Chemotherapy was given to 21 infants, according to various chemotherapeutic protocols. During the postoperative period 20 deaths (39%) were recorded. Two patients were lost to follow-up. From 1 to 10 years after the operation, 29 patients are still alive, 14 of them (28%) with a normal psychomotor development, 10 (20%) with some neurological or mental deficits, and 5 (10%) with severe psychomotor retardation. There was no apparent correlation in this series between late outcomes and the histological type of the tumour. PMID- 8213274 TI - One-year outcome in early aneurysm surgery: prediction of outcome. AB - Predictors of one-year outcome were studied in patients treated for ruptured intracranial aneurysm. A total of 929 patients, who were treated conservatively or surgically, and 839 patients as a part of this population who were surgically treated, were randomly divided into two groups in order to create predictive models by logistic regression and to validate them. The models were derived from two-thirds of these two patient groups and the remaining one-thirds were used for validation. The pre-operative variables of both conservatively and surgically treated patients were studied by Model A. The pre-operative Grade (Hunt and Hess), age, and the presence of vasospasm on angiography were the three most important predictors of the one-year outcome (Glasgow Outcome Scale 1-2/3-5). Model B consisted of pre- and per-operative, and Model C pre-, per-, and post operative variables collected from the surgically treated group. The pre operative Grade, ligation of a major vessel and age were the three most powerful determinants of outcome in Model B. In Model C high Grade, post-operative CT hypodensities and ligation of a major vessel were most closely associated with poor outcome. Model A, based on pre-operative data, most accurately predicted good outcome. All the 59 patients in the validation sample (n = 310) who were predicted to have a less than 5% probability of poor outcome had a favourable outcome (positive and negative predictive value 100%). Model C determined that 22 of 280 patients would have a more than 80% probability of poor outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213275 TI - Open stereotactic amygdalohippocampectomy--clinical, psychometric, and MRI follow up. AB - The clinical results of six cases of open stereotactic amygdalohippocampectomy for medically intractable epilepsy are presented. Outcome in terms of seizure control (highly satisfactory in five patients) and neuropsychological sequelae (all cases had poor functioning of the contralateral temporal lobe pre operatively) are detailed. In addition the use of post-operative Magnetic Resonance Imaging (MRI) is demonstrated and shown to be a valuable tool in providing the crucially accurate baseline that is required for more meaningful follow-up outcome studies. PMID- 8213276 TI - Epilepsy in chronic subdural haematoma. AB - We studied retrospectively 143 adult patients treated in our department from 1979 to 1991 for chronic subdural haematoma (SDH) in order to identify the incidence of seizures and the necessity for prophylactic anticonvulsant treatment. Furthermore, after review of the literature, we selected an additional 879 cases for comparison. Results indicated a low incidence of epilepsy. Before surgery 5.6% of patients in our series and 4.3% in the literature had epilepsy, whereas after surgery, the frequencies were 3% and 1.8%, respectively. According to our data, antiepileptic drugs need not be administered prophylactically in patients with chronic SDH. But the situation is different for alcoholic patients, because they have a major risk of epilepsy. PMID- 8213277 TI - Routine use of the CO2 laser technique for resection of cerebral tumours. AB - The CO2 laser technique has been routinely used from 1988 through 1992 for the resection of 93 cerebral tumours (meningiomas 58%, gliomas 15%, neurinomas 9%, miscellaneous 18%). The CO2 laser technique was found the more effective 1) in tumours of hard consistency, 2) in large or giant tumours, 3) in tumours with scarce vascularization. Meningiomas were the indication of choice (54 cases that is 58% of all tumours treated with CO2 laser, and 64% of all meningiomas operated on during the same period). Among the meningiomas treated with the CO2 laser, 54% were located on the skull base. The CO2 laser beam provides good haemostasis of small vessels during the vaporization process. When attached to the operative microscope, the other advantages of the CO2 laser technique are: the absence of a handle-piece, the absence of manual manipulation of the tumour, the coaxiality of the laser beam with the visual beam. The disadvantages are: the rigidity of the coupled microscope-Laser arm, the smoke produced by the vaporization of hard tumours, the noise of the device. PMID- 8213278 TI - Failed back surgery syndrome. Part I: Analysis of the clinical presentation and results of testing procedures for instability of the lumbar spine in 171 patients. AB - The clinical presentation and diagnostic approach in 171 patients with a failed back surgery syndrome is presented and analyzed with respect to the mode of the primary discectomy-approach and type of resulting instability as well as results of internal fixation. The clinical picture and physical signs are quite distinct but the indication for internal fixation is only obvious in the presence of positive results of additional testing procedures such as the anaesthesia of articular nerves and trial immobilisation in a plaster jacket. Different types of instability of the lumbar spine occur in relation to the mode of the primary and/or secondary discectomy-approach(es). By application of this diagnostic protocol excellent, good, satisfactory, moderate and poor results were obtained in 87 (53%), 42 (26%), 23 (14%), 9 (6%), and 2 (1%) patients, respectively (final evaluation was possible in 163 patients). PMID- 8213279 TI - The role of early postoperative CT scan following surgery for herniated lumbar disc. AB - 40 patients underwent lumbosacral microdiscectomy in a 12 months period covering the years 1988-1989 in our center. For the purpose of the present study, we considered the 30 cases who underwent CT control of the operated interspaces and of the adjacent vertebral endplates. This was routinely carried out on the 3rd post-operative day. The present study failed to show correlations between early post-operative CT data and subsequent clinical results in this unselected series of patients. In fact an image suggesting persistent disc herniation was as a rule observed in spite of satisfactory clinical results, and other CT findings that have been considered of clinical significance, such as intraspinal air and low attenuation of disc space, were commonly observed in patients with an uncomplicated post-operative course. The present study suggests that early post operative CT appears to be of no value in the management of potential early complications of low-back surgery. The introduction of MRI appears to offer other possibilities in the evaluation and management of failed back surgery syndrome (FBSS). PMID- 8213280 TI - Phase contrast magnetic resonance of the spinal cord preliminary results in spinal cord arterio-venous malformations. AB - In spite of the recent advances in neuroradiology including the CT scan and the spin-echo-magnetic resonance (MR), accurate diagnosis of arteriovenous malformations (AVMs) involving the spinal cord is still based on selective angiography. This last procedure is invasive and needs to be repeated during the follow up. Phase contrast angio MR was performed with a 0.5 Tesla unit on 12 patients with an AVM involving the spinal cord (7 intramedullary AVMs, 4 perimedullary fistulas, and 1 dural fistula with perimedullary venous drainage); 4 of these were investigated before and after treatment. Angio MR showed abnormal vascular patterns within the spinal canal in all cases, without distinguishing between arteries and veins; the nidus of the intramedullary AVMs was displayed in all cases. Angio MR provided images of the whole AVMs comparable to the angiographic pictures, in contrast to the spin-echo MR, which provided only discontinued images of the vessels. The efficient range of velocity providing images varied, according to the type of the malformation (slow for dural fistulas, rapid for intra-medullary AVMs). In the 4 patients investigated after treatment, comparison of the images obtained before and after treatment permitted assessment of the degree of occlusion of the malformation. Finally, angio MR as a complement of spin-echo MR can now be used as a reliable tool for detection of spinal cord AVMs, assessing the indication for angiography, and, furthermore, it can probably replace most of the post-operative control angiographies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213281 TI - The function of the hypothalamo-pituitary axis in brain dead patients. AB - In order to find out the function of the hypothalamo-pituitary axis in brain dead patients, pituitary and hypothalamic hormone concentrations were measured and several anterior pituitary releasing tests were carried out in 39 brain dead patients. In addition, cerebral blood flow measurements were simultaneously performed. In almost all cases, the blood concentration of pituitary and hypothalamic hormones were above the sensitivity of the assay. Anterior pituitary releasing tests indicated that efficient functions of the hypothalamus were severely suppressed, while the normal secretory mechanism of the anterior pituitary was partially preserved in brain dead patients. Histological changes of hypothalamic neurons varied from barely detectable ghost cells to nearly normal cells even in the same case. Although, the remaining circulation seemed not to be sufficient enough to maintain integrated hypothalamo-pituitary function, as shown by the examinations of cerebral blood flow, the presence of hypothalamic hormones in the systemic circulation suggests that these hormones were released and carried from the hypothalamus by minimal flow which is preserved even after the diagnosis of brain death. PMID- 8213282 TI - Preservation of cochlear nerve function in acoustic neurinoma surgery. AB - A total of 55 cases with unilateral acoustic neurinoma which were operated on by the lateral suboccipital approach was studied to elucidate factors which influence postoperative hearing acuity. We analyzed several factors: preoperative hearing level, tumour size, tumour consistency (cystic or solid), and anatomical location of the cochlear nerve. The size of the tumours ranged from 1.2 to 5.8 cm in diameter. Thirty of 55 cases (55%) preoperatively had remaining cochlear function. The smaller the size of tumour, the higher was the preoperative hearing level excepting those tumours with a diameter of 5 cm or greater, which had relatively good hearing and often contained large cysts. As to the consistency of the tumours, 41 were solid and 14 were cystic, where 19 (46%) and 11 (79%) cases had had preoperative hearing, respectively. Anatomical continuity of the cochlear nerve was maintained at surgery in 15 of 30 cases with preoperatively remaining hearing; cochlear function was preserved after surgery in 9 of the 15 cases. It was located counter-clockwise (caudally) to the facial nerve at an angle of 50 degrees on average when they were projected on the right side. The distance or interrelation between the two nerves had no bearing on postoperative hearing preservation. Postoperatively, hearing acuity was improved in 6 cases (20%) with a mean value of 5.6 dB, unchanged in 3 (10%), and deteriorated in 21 (70%) among the 30 cases with remaining preoperative-hearing. When the tumour was less than 2 cm or cystic, better hearing preservation was expected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213283 TI - Hemoglobin penetration in the wall of the rabbit basilar artery after subarachnoid hemorrhage and intracisternal hemoglobin injection. AB - The ability of hemoglobin (Hb) to penetrate the basilar arterial wall in vivo after experimental subarachnoid hemorrhage was examined using immunohistochemistry. The distribution of anti-Hb antibodies in rabbit basilar artery was studied following the injection of autologous blood in the cisterna magna. Vessels removed two or four days after subarachnoid hemorrhage exhibited varying degrees of vasospasm, and exhibited Hb immuno-fluorescence throughout the vessel wall. Hemoglobin immunofluorescence was most conspicuous in the adventitia but was also seen in the smooth muscle and endothelial cell layers in 7 of 10 animals. The degree of vasoconstriction correlated with the total amount of Hb fluorescence present in the vessel wall. When Hb solution alone was injected into the subarachnoid space, vasoconstriction was evident but penetration into the vascular layers was not as extensive as that observed after injection of autologous blood. These findings demonstrate that Hb is able to penetrate through the arterial wall after subarachnoid hemorrhage. The results provide direct support for the hypothesis that Hb-induced changes in smooth muscle and/or endothelial function can contribute to the pathogenesis of vasospasm. PMID- 8213284 TI - Ascorbic acid and focal cerebral ischaemia in a primate model. AB - Neuronal cell damage following ischaemia is postulated to be due to free radical induced lipid peroxidation, and ascorbic acid is supposedly an important non enzymatic scavenger of such free radicals. This study was undertaken to evaluate the protective effect of ascorbic acid on the brain in a primate model after focal cerebral ischemia. Consumption of ascorbic acid in the monkey brain following ischaemia and its effect on macroscopic infarct size as demonstrated by 2, 3, 5, Triphenyl tetrazolium chloride (TTC) staining were used as parameters. The monkeys in the treated group were given 1 gram ascorbic acid parenterally every day for six days. The mean level of total ascorbic acid in right basal ganglia was 35.1 +/- 4.2 micrograms/mg of protein in the treated group as opposed to 22.9 +/- 2.1 micrograms/mg of protein in the nontreated group both before ischaemia. After right middle cerebral artery occlusion to produce focal cerebral ischaemia, the total ascorbic acid in the right basal ganglia 2 hours post ischaemia was 13.3 +/- 3.1 micrograms/mg of protein in the treated group as opposed to 9 +/- 1.6 micrograms/mg of protein in the untreated group. The average consumption of total ascorbic acid was 21.8 micrograms/mg of protein in the treated group and 13.9 micrograms/mg of protein in the nontreated group. Macroscopic infarct size as determined by TTC staining in the right cerebral hemisphere was 11.7 +/- 6.9 in treated group whereas it was 24.4 +/- 4.4 (expressed as percentage of right hemisphere) in the non-treated group. There was significant reduction in the size of the infarct in the treated group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213285 TI - CT-guided percutaneous selective cordotomy. AB - In this article the technique of CT-Guided Selective Cordotomy is described. The advantages of CT guidance in percutaneous cordotomy are the measurement of spinal cord diameters at the lesion site for each individual patient, direct visualization of target electrode relations, demonstration of spinal cord displacement during the procedure and localization of the electrode system in a specific part of the spinothalamic tract. Local destruction of the spinothalamic tract leads to selective cordotomy. Since 1987, CT-Guided Cordotomy has been applied to 54 cases of intractable cancer pain. In 33 of the 54 cases, the cordotomy was selective enough to be successful with a local denervation of the area where the pain was dominant. Except for one temporary hemiparesis and one temporary ataxia, no complications or side effects were observed. PMID- 8213286 TI - [Heterogeneity of eating disorders]. AB - This paper revises the literature which has attempted to define subgroups within the umbrella category of eating disorders, taking into account the heterogeneity of the clinical picture regarding personality structure, its linkage to eating behavior disorders, and differences in emotional expression. Research conducted over the last few years, in light of the new definition of these disorders proposed by DSM IIR, reinforces the differences between patients following a restrictive pattern and patients with bulimic episodes. PMID- 8213287 TI - [Reactive and adaptive phenomena in bronchial asthma]. AB - Psychological phenomena secondary to bronchial asthma play a relevant role in this disease influencing in a remarkable way its clinical course in each patient. Thus, an appropriate knowledge of the reactive and adjustment phenomena may lead to an outstanding medical outcome in response to the relevant conventional medical treatments usually carried out in these patients. In our present paper diverse psychosological variables involving psychological responders to a chronic disease as bronchial asthma are analysed. Such variables include so important topics as "illness behaviour", "life style", coping style" and treatment compliance in this very clinical condition. PMID- 8213288 TI - [Relation between psychological symptoms and gynecological, hormonal and perimenopausal disorders]. AB - This works consists of two parts. In the first part an epidemiological and diagnostic study is made of all the patients of climacteric age attended during a period of four years. One group is separated that reveals a similar psychopathological picture and by means of a process of statistical association you continue relating significantly to the gynecological-hormonal alterations that patients present. A subgroup is isolated that shows the highest probability of a significant association between the psychopathological picture and perimenopausal neurohormonal changes. In the second part an open clinical study is made of twenty patients who belong to the final subgroup resulting from the previous part. Two samples are made with ten patients in each. One of these samples is treated with standard psychopharmacological medication. The other sample is treated with a centrally acting drug with repercussions mainly on the neurovegetative climacteric alterations. A symptomatological improvement is shown un the second sample of patients that is significantly higher, a result which supports the hypothesis in the first part, concerning the final subgroup and the organic alterations characteristics of the climacteric. PMID- 8213289 TI - [Plasmatic concentrations of fluoxetine, pharmacokinetics, therapeutic response and side effects]. AB - The kinetics of fluoxetine and possible relations between the drug's plasmatic concentration and therapeutic response and side effects were evaluated in a sample of 66 depressive patients, 26 men and 40 women, average age 46.6 years (SD = 14.1), diagnosed according to DSM-III criteria and evaluated using the Hamilton scale for depression (17-item HRSD). We found no difference between plasmatic concentration of fluoxetine in weeks 3 and 6 of treatment, nor in the sum of drug plus active principle in weeks 3 and 6. There was no significant linear correlation between plasmatic concentrations of fluoxetine, norfluoxetine, or the sum of both in weeks 3 and 6 and score on the Hamilton scale in week 6. By means of serial Chi-score calculation we found a "minimum plasmatic concentration" of about 30 ng/ml below which there was less therapeutic response. PMID- 8213290 TI - [Application in medical students of the Zielke questionnaire for changes after group processes]. AB - It has been studied with the Zielken questionnaire the modification of second year medical students mental health symptomatology after two different group activities. The results showed that subjects who participate in any groups improved significantly when compared those of the sensitization treatment groups with those with control groups results indicates that sensitization groups subjects grew better than controls for the perception of professional difficulties. Internal locus of control for mood disturbances diminished more in control groups. PMID- 8213291 TI - Life stressors, drinking patterns, and depressive symptomatology: ethnicity and stress-buffer effects of alcohol. AB - This paper seeks to extend previous research on stress buffer effects of alcohol use using data from a tri-ethnic community sample of 1,784 respondents. Differences in buffer effects between Anglos, Blacks, and Mexican Americans are examined to explore possible racial/ethnic variation in the role or function of alcohol vis-a-vis life stress and depressive symptoms. Both acute life events and chronic financial stress are examined to clarify the conditions under which buffer effects are most and least salient in these groups. The findings indicate that alcohol buffer effects are most pronounced among males with regard to life event stress and depression. Ethnic differences in buffer effects were suggested among males for life events, though statistical controls for demographic factors, fatalism, and religiosity accounted for these differences. The implications of these findings are examined, and the paper generally highlights the need to view alcohol use and alcohol buffer effects in the context of more general coping orientations. PMID- 8213292 TI - Cigarette smoking: effects upon self-rated stress and arousal over the day. AB - Feelings of stress and arousal were assessed over a day of cigarette smoking. Smokers reported heightened stress prior to smoking, and reduced stress immediately after smoking (p < .002). Feelings of arousal were also significantly affected by cigarette use, with lower arousal prior to smoking, and increased arousal postsmoking (p < .011). This pattern was found with both "sedative" and "stimulant" smokers, as defined by the Smoking Motive Questionnaire (SMQ). These findings demonstrate that smoking can simultaneously produce both increased arousal and decreased stress. They lend doubt to the arousal modulation theory, which states that smoking leads either to reduced stress, or to increased arousal, but not both together. The present data broadly replicated some earlier findings (O'Neill & Parrott, 1992), and confirmed that smokers experience vacilating feelings of stress and arousal over the day. Thus, while feeling-state improvements often accompany cigarette smoking, they are followed by negative feelings (during nicotine withdrawal), which are alleviated by the next cigarette. These feeling-state changes also provide a clear psychological rationale for the repetitive/addictive nature of tobacco use. PMID- 8213293 TI - Factors promoting cigarette smoking among black youth: a causal modeling approach. AB - A longitudinal model of Black adolescent smoking was tested using 223 seventh grade students attending public schools in northern New Jersey. Interpersonal and intrapersonal factors were hypothesized to have an impact on Black seventh graders' decision to smoke. After conducting an exploratory Principal Factor Analysis (PFA) using a varimax rotation with the Time 1 data, a structural equation model was developed and refined through successive iterations. The final model revealed friends' smoking to be the most significant predictor of Black adolescent smoking at Time 1, but perceived smoking norms and intrapersonal factors such as decision making, self-efficacy, and self-esteem at home and at school exerted an important influence on smoking at Time 2. These results suggest that social influence factors may be important early in the smoking initiation process, but factors such as perceived smoking norms and intrapersonal factors may play an important role in maintaining the smoking habit in Black adolescents. PMID- 8213294 TI - Three approaches to adolescent smoking detection: a comparison of "expert" assessment, anonymous self-report, and co measurement. AB - A new method designed to assess adolescent smoking was recently developed and applied by researchers in the former Soviet Union. As originally applied in Lithuania and Russia, two official student leaders from each class were chosen to estimate smoking prevalence rates for their class, and so the method became labeled as the "expert assessment." Their findings suggested that this "expert assessment" method agreed quite well with school-wide prevalence estimates based on a survey of the entire school population. The purpose of the present study was to determine whether student representatives, selected at random and coached to accurately summarize the smoking habits of their classmates, could provide accurate estimates of the smoking prevalence rate in their school. To accomplish this purpose, estimates from the student representatives were compared to those from an anonymous survey and from measurement of carbon monoxide in expired air. The results indicated that the self-report and carbon monoxide data were in close agreement, while the student representatives substantially overestimated the prevalence of smoking in their school, in spite of the coaching provided according to the "expert assessment" protocol. Additional research on alternative methods to select student representatives, such as those based on a sociometric analysis, may yet result in a low-cost method to assess schoolwide levels of smoking in adolescent populations. PMID- 8213295 TI - Personality risk for alcoholism covaries with hangover symptoms. AB - Previous work relating self-reported hangover symptoms and familial risk for alcoholism was extended to personality risk for alcoholism, as measured by the MacAndrew alcoholism scale (MAC). The MAC predicted a significant amount of unique variance in reported hangover symptoms after controlling for gender, average quantity consumed on a drinking occasion, and fathers' scores on the Short Michigan Alcoholism Screening Test (SMAST). Individuals at elevated personality risk for alcoholism apparently experience more acute withdrawal and hangover, which may initiate further drinking to relieve these aversive symptoms. PMID- 8213296 TI - Validation of smoking abstinence in newly diagnosed cardiovascular patients. AB - Three methods of assessing smoking status among newly diagnosed cardiovascular (CV) patients were compared: self-reports, collateral reports (spouse, friend, etc.), and saliva cotinine assays. Self-reported smoking status was assessed as the average number of cigarettes smoked per day at baseline, 3, 6, 9, and 12 months into treatment, and at a 6-month posttreatment follow-up. The majority of patients had quit smoking within 6 months prior to participating in the program. All participants were informed at the onset of the study and at the time of each assessment that their self-reports of smoking abstinence would be validated through collateral reports and possibly saliva cotinine analyses. Less than 5% (13 of 274) of the subjects' self-reports showed discrepancies with collateral reports. Analyses of saliva cotinine assays in a subsample of subjects, however, indicated that 16% (13 of 81) of the saliva cotinine tests were discrepant with the collateral reports. Thus, the saliva cotinine analyses picked up an additional 11% false negatives, as compared to collateral reports. It is concluded that the use of collateral reports as an index of smoking status may be an overestimate of actual quit rates. The overall discrepancy rate for this study, however, was fairly low and suggests that patients' self-reports may be reliable when they have already quit on their own and/or are notified in advance of verification procedures. PMID- 8213297 TI - Examination of pretreatment predictors of attrition in a VLCD and behavior therapy weight-loss program. AB - Seventeen pretreatment predictors of attrition in a very low-calorie diet (VLCD) and behavior therapy combined weight-loss program (Optifast) were examined. A multiple discriminant function analysis was conducted on historical data in an attempt to distinguish early dropouts (weeks 2-14) from late dropouts (weeks 15 26) from completers. The following seven predictor variables contributed to the significant discriminant function equation: the number of past diets, past emotional difficulties, past physical or emotional difficulties while dieting, expected stress over the next 6 months, the number of close friends, the number of people who annoy the dieter about his or her weight, and the expectation of insurance coverage. In addition, it was found that completers reported a significantly greater number of previous diets than early dropouts. PMID- 8213298 TI - Habituation of electrodermal reactivity to visual alcohol stimuli in alcoholics. AB - This study address the question of cued reactivity in alcoholics. Twenty alcoholic in-patients and 20 control subjects were presented with repeated exposures to a alcohol-related (A) and a neutral (B) slide, in either an ABA or BAB sequence. Skin Conductance Level (SCL) and Skin Conductance Responses (SCR) were recorded. Alcohol-dependent subjects showed increased SCR compared to the control subjects. This was, however, independent of whether the presented stimuli were alcohol-related or neutral. Thus, the results did not support the hypothesis of cued reactivity, but point to a nonspecific hyper-reactivity in alcohol dependent subjects. The results are discussed in relation to risk-factors for alcoholism and relapse. PMID- 8213299 TI - Variability in subjective responses to cocaine: initial experiences of college students. AB - Eighty psychology students were administered a short self-report questionnaire that probed their initial and most recent experiences with cocaine. Most of the subjects were relatively inexperienced with cocaine; only five had used the drug more than 40 times. Measures of Global Positive and Global Negative responses to cocaine use were obtained. There was substantial variability in the response to cocaine on both the positive and negative effects scales, although there was no relationship between the magnitude of these self-reported effects of cocaine. The initial Global Positive (but not Global Negative) scores were correlated with latency to next use of cocaine and with lifetime use of the drug, suggesting that abuse potential of the drug is related to magnitude of initial positive effect. These data suggest that studies on predisposing factors in cocaine abuse should examine the basis for the variability in initial response to cocaine. PMID- 8213300 TI - Results of a year-long incentives-based worksite smoking-cessation program. AB - This study evaluated the impact of a year-long incentives-based worksite smoking cessation program. Nineteen moderate-sized worksites, employing a total of approximately 1100 smokers, were randomized to Incentive or No Incentive conditions. All identified smokers in the worksite were considered as subjects, whether or not they participated in the intervention. Analyses were conducted at both the worksite and individual level, and using both self-reported and biochemically validated cessation as endpoints. The incentive program did not significantly improve cessation rates at either the 1-year or 2-year follow-up assessments. We conclude that more broadly focused interventions that also address worksite smoking policies, skills training, and cessation resources, or programs that target additional risk factors are needed to substantially enhance quit rates. PMID- 8213301 TI - Eye movements in recovering substance abusers: a prospective study. AB - Smooth-pursuit (SPEM) and saccadic (SEM) eye movements were studied in 11 cocaine dependent and 4 alcohol-dependent patients after 1, 3, and 12 weeks of verified abstinence. Sixteen non-drug-dependent controls were studied after comparable intervals. SPEM tracking accuracy, estimated by the Ln (S/N) statistic, was higher among cocaine-dependent patients than among alcohol-dependent patients and normal controls. A microanalysis of SPEM tracking revealed that the superior accuracy of the cocaine-dependent group was due to a small increase in eye movements at the target frequency (0.4 Hz) and a small compensatory decrease in higher frequency eye movements (i.e., saccades). In contrast to the findings of the SPEM study, the findings of the SEM study revealed that alcohol-dependent patients constituted the only abnormal group. Alcohol-dependent patients exhibited slower saccade onset latencies than the other groups. There were no significant differences among the groups with respect to saccade velocity, amplitude, or duration. PMID- 8213302 TI - Can opiate addicts tell us about their relapse risk? Subjective predictors of clinical prognosis. AB - Given the high relapse rate of opiate addicts following detoxification, it is pertinent to identify whether any subjective variables mediate outcome, since these may then be targets of treatment. The present study assessed personality, cue-elicited craving, outcome expectancies for drug use, and self-efficacy for resisting drug use, in 43 opiate addicts receiving inpatient detoxification in either a specialist drug-dependence unit or a behavioral/general psychiatric ward, within the context of a randomised, controlled-treatment trial. Subjects were followed-up at between 1 and 3 months and again at 6 months after discharge. Frequency of drug use was not predicted by any of the subjective variables at the first follow-up; but at 6 months, subjects with lower self-efficacy and higher positive outcome expectancies were found to be using less often. Latency to first lapse was greater in subjects with higher anxiety and neuroticism scores. Precipitants to the first lapse were identified, but none of the predicted relationships between subjective variables and circumstances of lapse emerged. It is suggested that greater awareness of personal vulnerability may promote effective coping strategies. PMID- 8213303 TI - Nicotine gum use in the first year of the Lung Health Study. AB - Of 3,923 special intervention participants in the Lung Health Study who were offered nicotine gum to help them quit smoking, 1,080 (28.9%) were using nicotine gum 12 months after entry into the study. This group is comprised of 33.6% sustained nonsmokers, 54.5% intermittent smokers, and 19.2% continuing smokers. The average use of gum at 12 months is 7.3 pieces per day. At 12 months, men were significantly more likely to be nonsmokers than women, but women were significantly more likely to use gum than men. Among the sustained nonsmokers, continuous gum users reported significantly more mild side effects than those who used gum intermittently, although there were no differences in moderate or severe side effects between the two groups. Overall, the rate of observed side effects was small. Factors associated with nicotine dependence were related to the use and amount of gum use at 12 months. PMID- 8213304 TI - Medicinal and therapeutic value of the shiitake mushroom. PMID- 8213305 TI - Yeast lipid biotechnology. PMID- 8213306 TI - Pectin, pectinase and protopectinase: production, properties, and applications. PMID- 8213307 TI - Microbial pentose utilization. PMID- 8213308 TI - Genetically engineered microorganisms to rescue plants from frost injury. AB - Ice nucleation active bacteria belonging to genera Pseudomonas, Xanthomonas and Erwinia contribute to frost damage to plants by initiating the formation of ice in plants that would otherwise supercool and avoid the damaging ice formation. The biological control of frost injury can be achieved by the application of non ice nucleation active bacteria to the plant surfaces before they become colonized by Ice+ species. ice genes have been cloned from Pseudomonas and isogenic Ice- derivatives constructed via genetic manipulations. These genetically engineered microorganisms (GEMs) have been released into the environment to control the frost damage. The incidence of frost injury to the plants has, thereby, been reduced by 50-85% during natural frosts. These GEMs do not survive in soil and show no aerial dispersal in the environment. PMID- 8213309 TI - Synthesis of L-carnitine by microorganisms and isolated enzymes. AB - L-Carnitine, a quaternary ammonium compound, plays an important role in beta oxidation of fatty acids in mammals. The increasing demand for this compound in medicine has led to the development of numerous procedures for L-carnitine production. This review discusses the possibilities of microbial and enzymatical synthesis of L-carnitine and gives an overview on the pathways of L-carnitine metabolism and related enzymes in microorganisms. PMID- 8213310 TI - From the panniculus carnosum (PC) to the superficial fascia system (SFS) AB - There is a renewed interest in the anatomy of the subcutaneous fat. These studies have been stimulated by the recent clinical popularity of liposuction. Attention has been drawn to the superficial fascia system and to its role in wound healing and in skin contraction. What is the origin of this SFS? This article proposes that the panniculus carnosum (except for the platysma) did not disappear in man. Instead, it is present throughout the body as the superficial fascia system. Therefore, the superficial fascia system is nothing else but the evolutionary form of the panniculus carnosum. PMID- 8213311 TI - "No-touch" submuscular saline breast augmentation technique. AB - This article represents a retrospective view of the author's 17-year experience with 2863 saline implants in 1327 patients and details his "no-touch" technique. The experience included almost an equal number of submammary and subpectoral procedures. The submammary procedures were done early on and were replaced with subpectoral procedures, done exclusively at the present time. There were significantly less complications--capsules, wrinkling (visible folds), and deflations--with the subpectoral procedures. Followup is longer for submammary procedures which could be the reason for the slight difference in number of deflations. Analyzing the results from three different periods, during which the technique changed, the last period in which the no-touch subpectoral technique was used had markedly fewer complications. The no-touch technique, which had been introduced in orthopedic surgery over 50 years ago, was added to the augmentation procedure in an attempt to eliminate any possible contact with skin or breast bacteria. There were no infections in the entire series, and, during the no-touch period, capsules were almost eliminated (0.6%). Saline implants can achieve excellent results when placed subpectorally using the no-touch technique. PMID- 8213312 TI - Treatment of alar cartilages: should the "domes" be interrupted? AB - The author emphasizes that conservative rhinoplasty techniques are frequently satisfactory, but in certain techniques there is a limit to which nasal tips can be reshaped. In certain circumstances, therefore, interruption of the "domes" of the alar cartilages is suggested to achieve the most satisfactory aesthetic results. PMID- 8213313 TI - Syringe liposculpture revisited. AB - Syringe liposculpture was introduced by Fournier almost a decade ago. Recent advances have improved the technique, making it easier for the surgeon to use. To determine the efficacy of the syringe in reducing morbidity, groups of patients who had between 1200 and 1500 mL of adipose tissue removed were evaluated using different infiltration and power source (syringe vs machine) regimens. There was less blood lost when the syringe was used. In addition, syringe-treated patients appeared to heal faster, return to work in a shorter period of time, and have less pain. The advantages of the syringe technique are considerable and increase the safety factor of the liposculpture procedure. PMID- 8213315 TI - Reduction mammoplasty for macromastia. AB - Macromastia is a common cause of physical and emotional suffering. Reduction mammoplasty can provide relief from shoulder grooving, back and neck pain, intertrigo, and symptoms of ulnar nerve compression. Similarly, emotional well being is enhanced by improved self-image, increased capacity to participate in sports and work, and the ability to wear normal, attractive clothes. In the last three years, we have performed reduction mammoplasty using the inferior pedicle technique or free nipple graft in 75 patients. Preoperative symptoms typically included back pain, shoulder grooving, and a stooped posture. Fat necrosis was the most common complication and was associated with large resections. Patient satisfaction was high for both procedures. PMID- 8213314 TI - Experience with tumescent technique in lipoplasty. AB - Tumescent injection of tissues in preparation for suction lipectomy appears to be safe and effective. It allows lipoplasty of a wide range of volumes and areas in an office setting under oral sedation and without the need for fluid replacement. Few plastic surgeons believe this or have experience with the technique. This article documents the study of the characteristics of tumescent injection, demonstrates its effectiveness and utility, and addresses issues raised by those who doubt that this is a major improvement in accomplishing suction lipectomy. One hundred consecutive cases were treated over two and a half years without using any intravenous fluid or intravenous medication. Results of this survey are tabulated and discussed. They show the safety and advantages of this adjunct to lipoplasty. PMID- 8213316 TI - A no bleed implant. AB - Breast implants have evolved from the original saline-filled, smooth-surfaced silicone rubber bag to silicone gel-filled smooth-walled sacs to a combination of a silicone gel-filled bag within a saline-filled sac, and, most recently, a reversed, double-lumen implant with a saline bag inside of a gel-filled bag. Texture-surfaced implants were first used in 1970 when the standard silicone gel filled implant was covered with a polyurethane foam. Because of concerns about the degradation products of this foam, they were removed from the market in 1991. In 1975 double-lumen silicone textured implants were developed, followed by silicone gel-filled textured implants. In 1990 a new radiolucent, biocompatible gel was produced that reduced the problem of radioopacity of silicone implants. Because of the gel's sufficiently low coefficient of friction, leakage caused by fold flaw fracture may also be decreased. We present a case where this new biocompatible gel implant was repositioned after four months. The resulting scar capsule in this soft breast was thin [< 0.002 cm (0.008 in.)] and evenly textured as a mirror image of the textured silicone surface. Scanning electron microscopy and x-ray defraction spectrophotometry revealed no silicone bleed. PMID- 8213317 TI - Another look at steroids: intraluminal methylprednisolone in retropectoral augmentation mammoplasty. AB - The authors report some preliminary results with 150 patients who had a retropectoral augmentation mammoplasty using double-lumen prostheses with intraluminal steroids. Two control groups were also studied: one (35 patients) with steroids placed in only one prostheses and the other (25 patients) with steroid-free prostheses. The use of double-lumen prostheses which might decrease the steroid diffusion rate, and retromuscular positioning of the prostheses may account for the results obtained. The data obtained from the three groups indicate that steroids might have a significant and safe role in preventing capsular contracture. PMID- 8213318 TI - Calf augmentation with new solid silicone implants. AB - Calf augmentation has been standardized by the use of banana-shaped silicone gel implants for almost 20 years. Capsule formation and resulting distignement, dislocation, gel bleeding, and implant rupture are rare but unpleasant complications. A new implant of solid silicone (McGhan, Santa Barbara, CA, USA) in the anatomical shape of one belly of the M. gastrocnemius placed subfascially appears to overcome these problems. PMID- 8213319 TI - Aesthetic incision in the subcutaneous forehead lift. AB - The forehead plays a relevant role, perhaps the most important role, in what we shall call the topographical area of the orbital rims, since it flaccidity causes the eyebrows to droop, thus dragging down the upper eyelid and producing skin redundancy. Most published works on the subject of the forehead lift describe the classic coronal incision, with subgalea dissection involving an individualized design for each patient, according to the density of the hair. However, when the forehead has hair growing high on the head, the coronal incision becomes an anterior incision, following the first hairline. However, this has the same problems as the coronal incision, namely, anesthetizing the posterior part of the scar and, in some cases, depression of the scar on the edge of the flap caused by the retraction of the galea and the inadequate elimination of forehead furrows. Over the past two years, the author has used a nonlinear anterior incision with subcutaneous dissection in many select cases. PMID- 8213320 TI - Subperiosteal lateral browlift and its relationship to upper blepharoplasty. AB - Skin redundancy of the upper eyelid is often associated with a variable degree of ptosis of the lateral third of the eyebrow, which increases the extent of the defect. Correcting this condition implies a combination of a temporal lift with a standard upper blepharoplasty. In the temporal lift it is possible to perform an easy subaponeurotic and subperiosteal dissection of the soft tissues of the temporal area through an incision behind the hairline with pleasing and long lasting results. The brow ptosis is corrected without noticeable scars and with inconspicuous damage to scalp follicles of the temporal region. PMID- 8213321 TI - A new approach to the treatment of facial aging: the three flap SMAS. AB - In treating facial aging there are three areas that need to be corrected from a deep to a superficial plane. Thus, different techniques need to be used. In this article we describe our experience in correcting these three areas and a possible solution: the three flaps of the SMAS. PMID- 8213322 TI - Treatment of traumatic earlobe clefts. AB - Torn and split earlobes are common and often due to earring trauma. Repair of split earlobe clefts is one of the most common problems in plastic surgery. However, little has been written recently about this subject. This article compares our technique for repairing cleft earlobes with other described techniques. The technique presented is sound, simple in concept, technically undemanding to perform, and has definite advantages over other methods currently in use. A waiting period before repiercing the ear is suggested to allow the earlobe tissue to soften and assume its final shape. Neither recurrence nor notching of the lobule has been a problem. PMID- 8213323 TI - Instrument technique in scalp dissection for tissue expander placement. PMID- 8213325 TI - The caging phenomenon. PMID- 8213324 TI - An intraoperative patient stabilization device. AB - An intraoperative patient stabilization device is described for use in aesthetic breast surgery. This simple device maintains the patient in the vertical position throughout the many positional changes during aesthetic breast surgery. PMID- 8213326 TI - Ageing as a global issue. PMID- 8213327 TI - Cranial computed tomography of elderly patients: an evaluation of its use in acute neurological presentations. AB - We assessed the use of cranial computed tomography (CT) in elderly patients with acute neurological deficit and its influence on patient management. Clinical notes from 100 consecutive CT referrals from geriatric admissions presenting with acute neurological deficit were reviewed and categorized according to clinical presentation. CT results and subsequent therapy were recorded. Twenty of the patients had treatable lesions (in 6 out of 14 patients with signs atypical of stroke and 7 out of 19 patients with acute confusion). These two groups contained 68% of all treatable lesions found. Forty-four scans yielded no new diagnostic information; these included all scans for transient ischaemic attacks and for progression of stroke. The remaining scans yielded information regarding pathology but did not alter patient management. CT is a valuable first-line investigation in elderly patients presenting with signs atypical of stroke and unexplained confusion but may be less useful in patients with other presentations. PMID- 8213328 TI - A study of nutritional deficits of long-stay geriatric patients. AB - Current information suggests that dietary intake of nutrients declines with age and that undernutrition in elderly long-stay hospital patients may be under recognized. We undertook to describe the daily dietary intakes of a group of elderly long-stay hospital patients (n = 92) (group A), using 7-day weighed dietary records. The aim of the study was to determine the adequacy of the diet and investigate whether any differences existed in the intakes of the hospital patients. An assessment of nutritional status was carried out by anthropometry, haematology and biochemistry and was validated by comparison with two further groups: fit young subjects (n = 41) (group B) and fit community elderly subjects (n = 92) (group C). Men in group B had the highest mean values for mid-arm circumference, arm-muscle circumference, corrected arm-muscle area and arm-fat area while women in group A had the lowest mean values for all measured anthropometric indices. There were significant correlations between daily energy intake and anthropometry for men in groups B and C. In group A 68% had intakes < 2/3 recommended daily allowance for energy, 100% for vitamin D, E, B6, folic acid; 98% for magnesium and zinc; and 90% for retinol. Serum calcium and serum alkaline phosphatase were correlated with vitamin D intake in men in group A. There was no biochemical or haematological evidence of undernutrition in the three groups. Elderly long-stay hospital patients were grossly undernourished and their dietary intake did not satisfy basal metabolic demands, based on recommended daily allowances. PMID- 8213329 TI - Role of serology in monitoring treatment for Helicobacter pylori infection in elderly patients. AB - Fifteen elderly patients with type B gastritis caused by Helicobacter pylori infection were treated with triple therapy consisting of colloidal bismuth subcitrate, amoxycillin and metronidazole. All were followed up every 6 weeks for 3 months. After triple therapy, eradication of the infection was confirmed in 12 patients (85%) by histology and bacteriology. In this group, a significant reduction in IgG antibody levels against H. pylori was detected (p < 0.001). In a control group of 15 patients with type B gastritis who received no antibacterial treatment, the specific IgG antibody titre remained unchanged during 3 months of follow-up. We conclude that this simple and noninvasive serological test would be suitable for follow-up after treatment of H. pylori infection in elderly patients. PMID- 8213330 TI - Delay in diagnosis of colorectal cancer in elderly patients. AB - The medical histories of 178 colorectal cancer patients were studied retrospectively from hospital records. The average age at the time of diagnosis was 71 years. Visible loss of blood or anaemia were the commonest features. The mean time from first symptom to first medical consultation was 82.8 days. Men under 65 years and women over 80 years waited the longest time before consulting a physician. The mean time from the first medical consultation to diagnosis was 44.7 days. The delay was longer for men than for women but longest for women aged over 80 years. Information about digital rectal examination was lacking in over half of all patients and in two-thirds of patients over 80 years. In patients in whom rectal examination had been made, as many as 60% of rectal cancers were digitally palpable. Barium enema missed the cancer diagnosis in 11.2% of patients at the first examination; the missed cancers were located in the sigmoid area and in the right colon. Colonoscopy can be recommended as the primary investigation method when colorectal cancer is suspected. Re-examination is necessary in elderly patients with sideropenic anaemia if the first examination is negative. PMID- 8213331 TI - Four-compartment model of body composition of normal elderly women. AB - A group of 186 apparently normal women was divided into three age groups (average ages 65.3 +/- 4.4, 74.7 +/- 5.5, and 80.9 +/- 4.2 years, respectively) and their body composition was studied using dual-energy X-ray absorptiometry. The fat, fat free, and mineral components were quantitated, and the fat-free compartment was calculated to define a four-compartment model of body composition (fat, fat-free, mineral, and water). Fat decreases with age, as shown by the comparison of the group whose average age was 75 years with the 65-year-old group (p < 0.01) and 80 year-old group (p < 0.005). Soft-tissue mass was greater in the 80-year-old group (p < 0.025) than in the 75-year-old group. Water was lower in the two older groups (p < 0.02 and p < 0.005, respectively), and the mineral component showed no differences. The decreased fat, increased soft tissues, and absence of changes in the mineral component may be related to an improvement in habits and lifestyle in recent years. PMID- 8213332 TI - Arterial oxygen saturation and posture in acute stroke. AB - Patients with acute stroke are at risk of hypoxaemia and the degree of oxygen desaturation may depend on posture. Using a fingertip pulse oximeter, we studied the effects of different nursing positions on arterial oxygen saturation (SaO2) in ten elderly patients within 48 hours of a hemiplegic stroke and 10 age-matched controls admitted to hospital with other acute illnesses. Mean SaO2 was consistently higher in the controls than the stroke patients in all recumbent positions, but when patients were propped up the difference between the groups was statistically insignificant. The difference between semirecumbent and lying SaO2 values was then tested in a further nine stroke patients. Overall the mean SaO2 was significantly higher and, in at least four cases, the duration of episodes of desaturation (SaO2 < 90%) was substantially less when the patients were propped up. We suggest that, wherever possible, acute stroke patients should be nursed sitting up to minimize the risk of oxygen desaturation and possible aggravation of ischaemic brain damage. PMID- 8213333 TI - Seasonal variation of serum lipids in an elderly population. AB - We investigated seasonal variation in serum lipids in 96 volunteers aged 65-74 years who were studied at 2-monthly intervals for one year. Periodic regression analysis revealed highly significant seasonal variation in serum total cholesterol and high-density lipoprotein (HDL) cholesterol. Peak levels for both occurred in winter with corresponding summer troughs. The seasonal difference for total cholesterol was 0.32 mmol/l (95% CI 0.23-0.41, p < 0.0001) and that for HDL cholesterol 0.16 mmol/l (95% CI 0.12-0.19, p < 0.0001). Low-density lipoprotein (LDL) cholesterol was highest in winter in men only (seasonal difference 0.27 mmol/l, 95% CI 0.15-0.39, p < 0.0001), and triglycerides were significantly greater in late winter for women only (seasonal difference 0.22 mmol/l, 95% CI 0.09-0.35, p = 0.002). The timing of seasonal variation in total cholesterol and triglycerides would be consistent with a role in the seasonal variation in vascular deaths, but our finding of a relatively high HDL: total cholesterol ratio in winter makes this less likely. PMID- 8213334 TI - A pilot leg ulcer clinic in a geriatric day hospital. AB - Twenty-six patients with leg ulcers with a mean age of 80 years were assessed at a day hospital to determine the aetiology and to carry out a trial of four-layer compression bandaging for those suitable. Ten had ankle brachial pressure indices (ABIs) < 0.8. Of nine patients with venous disease who received compression bandaging, only two ulcers healed and have remained healed with fitted below-knee elastic stockings. The remaining patients were unable to tolerate compression or developed deterioration of their ulcers. Nine patients had unhealing arterial ulcers all unsuitable for reconstructive surgery. Five patients presented with pressure sores due to bandages, shoes or heel pressure in bed. All healed slowly with leg elevation and pressure relief. Four patients had extensive non-venous, non-arterial ulceration associated with fluid retention and dependent oedema exacerbated by spending their nights in chairs. Varicose eczema was healed in 12 patients. All the patients had multiple pathology and poorly controlled pain. Although complete healing was achieved in only six patients, the importance of ABI measurement and the gross mixed pathology suggests that every elderly patient with a leg ulcer needs medical assessment and management and that this could form a valuable service of a geriatric day hospital. PMID- 8213335 TI - Epidemiology of proximal femoral fracture in Gran Canaria (Canary Islands). AB - An epidemiological survey of proximal femoral fracture (PFF) was carried out in Gran Canaria (Canary Islands) in 1990. We identified 211 cases of PFF affecting residents, which gave an incidence of 161 per 100,000 per year (92 per 100,000 per year for men and 176 for women). Three quarters of all fractures occurred to residents of urban areas and nearly all fractures were caused by falls indoors. There was a higher incidence in winter than in summer months. PMID- 8213336 TI - The association of age with the presentation and outcome of tuberculosis: a five year survey. AB - Of the 411 patients notified with tuberculosis in Leeds during 1986 through 1991, case notes were available on 406 (99%) and the diagnosis of mycobacterial disease was accepted in 397 (98%). Twenty-two patients had infection with atypical mycobacteria and were excluded from analysis, as were children under 16 years. Comparison between the age groups was further restricted to white patients because of a skew distribution of Asian patients towards the younger age range. Ninety-six elderly patients (aged 65 years and older) were compared with 127 younger patients. The distribution of pulmonary and extrathoracic disease was similar as was the incidence of positive bacteriology. Elderly people had more frequent lower-zone and more frequent miliary shadowing, otherwise radiographic features were similar. Elderly people were nearly three times more likely to have reactions to antituberculous drugs, six times more likely to die from tuberculosis and over twenty times more likely than younger patients to have the diagnosis made at autopsy rather than during life. PMID- 8213337 TI - Are elderly people at risk of falling taught how to get up again? AB - It is recommended that patients at risk of falling should be taught how to get up from the floor. Clinical experience suggests, however, that this is rarely done. A stratified random sample of members of the special interest group of physiotherapists working with elderly people in England and Wales (PT: n = 50) and all members of the corresponding occupational therapy group (OT: n = 41) were surveyed to ascertain whether or not this impression was justified. The response rate was 80% with 67 usable replies (74%, PT: n = 38, OT: n = 29). Replying to an open-ended question about their usual management of instability and tendency to fall, only four physiotherapists (11%) and six occupational therapists (21%) indicated that would they teach such elderly people how to get up from the floor. PMID- 8213338 TI - Hypothesis: Healthy Active Life Expectancy (HALE) as an index of effectiveness of health and social services for elderly people. PMID- 8213339 TI - Review: silent exertional myocardial ischaemia and perception of angina in elderly people. PMID- 8213340 TI - Do we need clinical pharmacology? A personal view from Eastern Europe. AB - Despite the fact that clinical pharmacology is already an established discipline in many (developed) countries, in Eastern Europe it has not yet been fully recognized and therefore its development has lagged. On the basis of the WHO recommendations--together with the planned medical educational reform--it would be desirable to establish university departments of clinical pharmacology, not only to provide a better education but also to fulfill the needs of society. PMID- 8213341 TI - Third World conference on variability in response to anti-rheumatic drugs, Singapore, July 22-24, 1992. PMID- 8213342 TI - Pharmacological profile of new thioperamide derivatives at histamine peripheral H1-, H2-, H3-receptors in guinea-pig. AB - The recent availability of potent and selective ligands, namely R-(alpha) methylhistamine and thioperamide, led to conclusive progresses as regards histamine H3-receptor knowledge. The aim of this work is to investigate by in vitro tests the pharmacological properties of new amino and methyl derivatives of the H3-antagonist thioperamide. Such original compounds, developed by the modulation of the thioperamide imidazolyl moiety, were assayed at guinea-pig ileal contractile H1-, atrial chronotropic H2- and enteric neuronal H3-receptors. None of the drugs exhibited interaction with H1 or H2 sites. On electrically stimulated ileum, two of the thioperamide methyl derivatives competitively antagonized the inhibitory effect of the H3-agonist R-(alpha)-methylhistamine. On the basis of the Schild analysis, the more active isomer (compound IV) displayed an affinity at H3-receptors only five times lower than thioperamide. These results could contribute to elucidate further the structural features required to develop potent and selective H3-antagonists. On the other hand, to prove the hypothesized apparent heterogeneity between peripheral and central H3-sites, as emerged by pharmacological and binding studies, autoradiographic investigations are in progress. PMID- 8213344 TI - The properties of A-69412: a small hydrophilic 5-lipoxygenase inhibitor. AB - A compound which inhibits leukotriene biosynthesis could be clinically useful in treating several allergic and inflammatory diseases. One site for such inhibition is at the enzyme 5-lipoxygenase. Most inhibitors of this enzyme thus far described are poorly bioavailable. A-69412 is a small, relatively hydrophilic compound of the N-hydroxyurea class, which exhibits minimal plasma protein binding (6-12%). The compound was found to be a potent long-acting inhibitor of leukotriene formation in vivo in the rat (oral ED50 = 5 mg/kg) and ex vivo in several species. In addition, the compound exhibits excellent bioavailability in dogs and monkeys with a relatively long elimination half-life in both the species (6 and 3 h, respectively). The biochemical activity and pharmacological profile of A-69412 indicates its potential utility in asthma and ulcerative colitis, and possibly other inflammatory and allergic conditions. PMID- 8213343 TI - A 5-lipoxygenase inhibitor, FR110302, inhibits ozone-induced airway hyperresponsiveness in guinea pigs and dogs. AB - Airway hyperresponsiveness is a key feature of asthma, and attenuating airway hyperresponsiveness is an important part of asthma therapy. In the present study we examined the inhibitory effect of a potent 5-lipoxygenase inhibitor, FR110302, on airway hyperresponsiveness induced by ozone exposure in guinea pigs and dogs. Respiratory resistance (Rrs) was measured by a forced oscillation method. Airway responsiveness was determined from the dose-response curve of Rrs to acetylcholine. Guinea pigs were exposed to 2.5 ppm ozone for 1 h. In a control group of guinea pigs, delta log PC100 (the index of the ozone-induced airway hyperresponsiveness) was 0.58 +/- 0.04 (log mg/ml). Treatment with FR110302 (10 or 100 mg/kg p.o.) significantly diminished delta log PC100 (10 mg/kg: 0.22 +/- 0.10; 100 mg/kg; 0.11 +/- 0.06). Dogs were exposed to 3 ppm ozone for 2 h. In a control group of dogs, delta log Dmin (another index of the ozone-induced airway hyperresponsiveness) was 1.24 +/- 0.15 (log unit). Treatment with FR110302 (1 or 3.2 mg/kg p.o.) significantly diminished delta log Dmin (1 mg/kg: 0.60 +/- 0.18; 3.2 mg/kg: 0.27 +/- 0.12). These results suggest that FR110302 may be a useful drug for attenuating airway hyperresponsiveness in asthmatic patients. PMID- 8213345 TI - In vitro pharmacology of BAY X1005, a new inhibitor of leukotriene synthesis. AB - BAY X1005, (R)-2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl acetic acid, is an enantioselective inhibitor of leukotriene biosynthesis. It effectively inhibits the synthesis of LTB4 in A23187-stimulated leukocytes from rats, mice and humans (IC50 0.026, 0.039 and 0.22 mumol/l, respectively) as well as the formation of LTC4 (IC50 0.021 mumol/l) in mouse peritoneal macrophages stimulated with opsonized zymosan. The compound is, however, less active in inhibiting LTB4 synthesis in human whole blood (IC50 17.0 and 11.6 mumol/l, as measured by RIA or HPLC, respectively). BAY X1005 exhibits a high enantioselectivity in human whole blood (31 times over the (S)-enantiomer). BAY X1005 is shown to be a selective inhibitor of the formation of 5-lipoxygenase-derived metabolites in vitro, without effects on other routes of arachidonic acid metabolism such as 12 lipoxygenase in human whole blood and cyclooxygenase in both mouse macrophages and human whole blood. BAY X1005 is devoid of any antioxidant activity (methemoglobin induction and xanthine-xanthine oxidase assay), without effects on granule release and with only weak effects on reactive oxygen species generation in human PMNL. PMID- 8213346 TI - Piroxicam-copper complexes: inhibition of polymorphonuclear leukocyte migration to Pseudomonas aeruginosa chemotactins in vivo and superoxide dismutase-like activity in vitro. AB - Piroxicam-copper (Cu2+) complexes, formed spontaneously by mixing solutions of piroxicam and CuSO4 (1:1 Cu2+:piroxicam), inhibited the superoxide anion catalyzed reduction of ferricytochrome C in a dose-related fashion. Addition of ethylenediaminetetraacetate to the mixture decreased in a dose-related manner the superoxide dismutase (SOD)-like activity of piroxicam-Cu2+. Piroxicam alone (10( 5) M, final concentration) did not display SOD-like activity but 10(-5) M Cu2+ exhibited significant activity, similar to that of piroxicam-Cu2+. Intraperitoneal treatment of mice with either 0.64 mg/kg piroxicam or its Cu2+ complexes (0.64 mg/kg piroxicam + 0.12 mg/kg Cu2+) was equally effective in diminishing both the migration of polymorphonuclear leukocytes (PMNL) to the airways and the content of myeloperoxidase activity in the lungs, induced by aerosol challenge with Pseudomonas aeruginosa peptide chemotactins. Therefore, piroxicam-Cu2+ complexes may provide both the anti-inflammatory activity of piroxicam plus the SOD-like activity of Cu2+. PMID- 8213347 TI - Differential inhibition of human secretory and cytosolic phospholipase A2. AB - The roles and relative contributions of secretory and cytosolic phospholipases A2 in physiology and pathology are not precisely known. In a search for differential inhibitors of these enzymes, which could serve as tools to clarify this issue, we evaluated the potencies of reference compounds and three series of new compounds, viz. substrate analogues, 1,2-amino alcohols and enolized beta-tricarbonyl derivatives, as inhibitors of secretory phospholipase A2 from human polymorphonuclear leukocytes (sPLA2) and of cytosolic phospholipase A2 from human U937 cells (cPLA2). With few exceptions, the compounds selected are potent inhibitors of sPLA2 with IC50 values (concentration inhibiting 50%) in the low micromolar range. Inhibition of cPLA2 was only observed with some phosphate-free substrate analogues, with 1,2-amino alcohols and two of seven reference compounds. These results suggest that inhibition of secretory and of cytosolic phospholipases A2 are independent effects. Several inhibitors could be identified with a marked selectivity for sPLA2. PMID- 8213348 TI - Synthesis and release of platelet-activating factor and eicosanoids in human endothelial cells induced by different agonists. AB - Production of platelet-activating factor (PAF) and eicosanoids by human umbilical vein endothelial cells (HUVEC) after stimulation with different agonists has been studied. Significant amounts of PAF were measured in the cellular fraction after treatment with thrombin (2 NIHu/ml), calcium ionophore A23187 (2 microM) and histamine (100 microM) (110.3 +/- 14.3, 80.7 +/- 19.2 and 119.2 +/- 22.4 pg/10(5) cells, respectively). Only thrombin caused a partial release of PAF into the supernatant. IL-1 alpha (0.1 nM), TNF (1 nM), arachidonic acid (10 microM) and endothelin (0.1 microM) were not able to induce any PAF synthesis. High levels of 6-keto-PGF1 alpha were found after stimulation with thrombin and calcium ionophore A23187 (8641 +/- 2575 and 6715 +/- 3340 pg/10(5) cells, respectively). Cytokines IL-1 alpha and TNF were also able to stimulate PGI2 synthesis, although to a lesser extent. PGE2 production increased after treatment with thrombin and calcium ionophore A23187 three- and two-fold, respectively. Our results confirm that stimulated HUVEC are able to synthesize PAF and eicosanoids simultaneously, the relative amounts depending upon the agonist used. None of the agonists studied showed any significant effect on 15-HETE production. PMID- 8213349 TI - Pharmacokinetics and biological activity of kinetensin in conscious sheep. AB - Kinetensin is a nonapeptide, originally isolated from pepsin-treated plasma, that shares some sequence homology with the C-terminal end of neurotensin. The present study was designed to determine, by infusing kinetensin to conscious sheep, the pharmacokinetics and a neurotensin-like biological activity (pancreatic polypeptide response) of kinetensin. Kinetensin was rapidly metabolized, approximately 200-fold more rapidly than neurotensin. The majority of the metabolism occurred in the circulation as demonstrated both in vivo and in vitro. The lung and gut cleared kinetensin also. Inhibition of converting enzyme, present in highest concentration in the lung, abolished lung clearance but was without effect on kinetensin metabolism by the gut or in the general circulation. Arterial infusion of kinetensin which achieved high blood kinetensin levels at the pancreas did not increase plasma pancreatic polypeptide. We conclude that the extremely rapid degradation of exogenous kinetensin, together with the lack of biological activity, makes it unlikely that kinetensin plays a role as a circulating regulatory peptide. Nevertheless, since the putative kinetensin substrate circulates at microM concentrations, it is feasible that kinetensin is generated and metabolized at the target organ. PMID- 8213350 TI - Effects of gold sodium thiomalate, cyclosporin A, cyclophosphamide, and placebo on collagen-induced arthritis in rats. AB - The prophylactic and therapeutic effects of gold sodium thiomalate, cyclosporin A, cyclophosphamide, and placebo on collagen-induced arthritis (CIA) were evaluated in DA rats. Prophylactic treatment with cyclosporin A and cyclophosphamide suppressed the arthritis incidence, clinical inflammation, destructive bone changes, and development of anti-collagen antibody in DA rats subsequently injected with porcine type-II collagen. Therapeutic treatment with cyclosporin A and cyclophosphamide had a definite suppression on established CIA when started 21 days after the initial collagen injection, but the suppression was less marked than that of prophylactic treatment. Gold had no impact on CIA in DA rats when administered either prophylactically or therapeutically. PMID- 8213351 TI - Interleukin-1 (IL-1) production in a mouse tissue chamber model of inflammation. I. Development and initial characterisation of the model. AB - A simple and reliable animal model to quantify interleukin-1 (IL-1) production at a site of inflammation has been developed and characterised. This model involves the subcutaneous implantation of sterile Teflon chambers (30 mm x 10 mm diameter) into the backs of mice. After 14 days, a straw coloured transudate fluid was present in the lumen of the implanted chamber which was withdrawn for the determination of baseline measurements of various inflammatory parameters. A localised chronic inflammatory response was then induced in the chambers by injection of 1% zymosan or Bordetella pertussis vaccine (BPV) (in presensitised animals). The local inflammatory reaction in the chamber, over a 30 day time course, was characterised by leucocyte infiltration, and marked increases in protein, prostaglandin E2, IL-1 and IL-6 concentrations in the chamber fluid. A rapid increase in plasma concentrations of the acute-phase reactant serum amyloid P (SAP) also occurred. This model allows repeated samples to be obtained from the same animal for the assessment of inflammatory parameters and may be useful for investigating the mechanisms controlling the production of IL-1 during the inflammatory response in vivo. PMID- 8213352 TI - Interleukin-1 (IL-1) production in a mouse tissue chamber model of inflammation. II. Identification of (tissue) macrophages as the IL-1 producing cells and the effect of anti-inflammatory drugs. AB - We have used our newly described mouse tissue chamber model [1], to investigate the process of IL-1 production in more detail. The inflammatory reaction in the tissue surrounding the implanted chambers was investigated histologically and by using the polymerase chain reaction (PCR). The inflammatory response included influx of leucocytes into the granuloma surrounding the tissue chamber, expression of IL-1 beta on macrophages present in the inflamed tissue and an increase in the mRNA coding for IL-1 beta and IL-6 proteins in the granuloma. The effects of three anti-inflammatory or immunosuppressive drugs, prednisolone, indomethacin and cyclosporin A, on IL-1 beta and PGE2 production in zymosan and Bordetella-pertussis-vaccine (BPV)-challenged tissue chambers were also examined. Oral treatment with prednisolone and cyclosporin A of zymosan-challenged animals showed a dose-dependent reduction of IL-1 beta concentrations, but no effect of indomethacin. Both prednisolone and indomethacin dose-dependently reduced PGE2 concentrations to control levels, while cyclosporin A was effective only at the highest dose tested (100 mg/kg/day p.o.). In drug-treated BPV-challenged animals, prednisolone and cyclosporin A also showed a dose-dependent reduction of IL-1 beta, while indomethacin was again ineffective. Prednisolone and indomethacin also dose-dependently reduced the PGE2 concentrations to control levels, whereas cyclosporin A was effective only at the highest dose tested (100 mg/kg/day p.o.). This model will be useful for investigating the mechanisms controlling the production of IL-1 beta from the mRNA level to the secretion of mature biologically active protein [1], and in the search for new drugs which could selectively interfere with this process. PMID- 8213353 TI - The effect of prenatal diazepam exposure on TNF-alpha production by rat splenocytes. AB - Prenatal exposure to diazepam and other benzodiazepines (BDZ) has been found to result in a marked reduction of T-lymphocyte proliferation during postnatal development of rats. In search for pathogenic changes underlying this effect, we investigated the mitogen lipopolysaccharide (LPS) and concanavalin A (ConA) stimulated release of tumour necrosis factor (TNF)-alpha by mixed splenocytes of male offspring from Long Evans rats treated with 1.25 mg/kg per day diazepam from gestational day 14 to 20. In response to LPS, TNF-alpha release was found to be significantly lower in mixed splenocytes of two- and four-week-old treated than in control offspring. However, at eight weeks of age, prenatally diazepam-treated animals showed a significantly higher LPS-induced TNF-alpha release than control rats. Since monocytes/macrophages represent a major source of TNF-alpha, additional experiments were performed on purified spleen macrophages and lymphocytes stimulated with LPS. TNF-alpha release was only detectable in supernatants of adherent spleen macrophages and not in supernatants of lymphocytes. Thus, our data indicate that a disturbance in TNF-alpha release from macrophages is involved in the deficient immune response of prenatally diazepam exposed rats. PMID- 8213354 TI - Apyrogenic synthetic desmuramyldipeptide, LK-409, with immunomodulatory properties. AB - The synthesis and some immunological characteristics of a new desmuramyl dipeptide 7-oxooctanoyl-L-alanyl-D-isoglutamine (LK-409) are presented. The effects of this compound were compared with those of N-acetylmuramyl-L-alanyl-D isoglutamine (MDP). The influence of LK-409 on the number of B and T cells in spleen and the number of peritoneal macrophages was studied; Jerne's plaque forming cells assay was performed to monitor the effect of B cell differentiation. The blast transformation of T cells stimulated with concanavalin A was used to detect the influences on T lymphocytes. The activation of macrophages was studied as well. In contrast to MDP, LK-409 was apyrogenic in the doses applied but had similar immunomodulatory properties. Tested immunological properties and the absence of pyrogenicity and low toxicity make LK-409 a candidate for an immunomodulatory drug and a model molecule suitable for studying and understanding the dual activity of the MDP and its analogues. PMID- 8213355 TI - Enhancing in vivo effect of propranolol on human lymphocyte function is not due to stereospecific beta-adrenergic blockade. AB - Immunoenhancing in vivo effects of beta-adrenergic blockers have been previously ascribed to a reduced beta-receptor-mediated immunosuppression. In the present study using a whole blood stimulation assay, the effects of a five-day treatment with the purified (R)- or (S)-isomer of propranolol (3 x 40 mg/day) on the polyclonal in vitro responsiveness of peripheral blood lymphocytes (PBL) of normothyroid and hyperthyroid persons were assessed. It is shown that both isomers likewise exhibit a significant enhancing effect on the proliferative response of PBL to T and B cell mitogens, which strongly argues for nonspecific effects of propranolol to be responsible rather than a specific beta-adrenergic receptor blockade. PMID- 8213356 TI - The effect of diclofenac and ketoprofen on halothane MAC in rabbit. AB - Non-steroidal anti-inflammatory drugs obviously act also on the central nervous system. We, therefore, studied the effect of diclofenac 3 mg/kg and ketoprofen 4 mg/kg on the minimum alveolar concentration (MAC) of halothane in 10 New Zealand White rabbits. After determination of halothane MAC, total doses of NSAIDs were administered intravenously as three subdoses: 12.5%, 37.5% and 50% of the total dose. Depth of anaesthesia did not increase significantly after the first two doses with either drug. With ketoprofen, halothane MAC increased after subdose 3 from 1.52 (SD 0.42) vol% to 1.9 (SD 0.36) vol% (p < 0.01). With diclofenac, halothane MAC increased after subdose 3 from 1.44 (SD 0.18) vol% to 1.60 (SD 0.39) vol% (ns). With both drugs, large interindividual differences of MAC appeared after full doses of NSAIDs. PMID- 8213357 TI - Dose-effect and evidence of escape of inhibition after indomethacin treatment in a synchronized model of bone resorption. AB - We previously showed that cyclooxygenase inhibition by indomethacin (7.5 mg/kg/d) prevented resorption in a model of synchronized remodeling. In the present paper, we (i) tested the effectiveness of three doses of indomethacin (2, 4, 7.5 mg/kg/d) in this model, and (ii) verified whether indomethacin action was sustained in time. For that purpose, on day 6 after induction, untreated controls were compared with a group treated for six days with indomethacin (7.5 mg/kg/d), and an interrupted treatment group (4 days indomethacin + 2 days free). Indomethacin inhibited resorption and total number of osteoclasts in a dose dependent manner. In the second experiment in the discontinued group, the resorption and total number of osteoclasts were similar to sham-treated animals. Indomethacin was still effective in the continuous treatment group; however, resorption was distinctly higher than in the rats treated for four days. These data indicate that despite cyclooxygenase inhibition, another metabolic pathway started resorption. The stoppage of prostanoid inhibition permitted the rapid and complete restoration of resorption. PMID- 8213358 TI - [Recent advances in the treatment of macular diseases]. PMID- 8213359 TI - [Effects of porcine pancreatic elastase-1 on the elastin in human trabecular meshwork--immunohistochemical studies: report 1]. AB - The aim of this study was to determine the localization of elastin and to estimate the influence of porcine pancreatic elastase-1 (PPE) and alpha 1 antitrypsin-elastase complex (alpha 1A-EL), a circulating form of PPE, on the elastin in human trabecular tissue. Trabecular tissues obtained from normal postmortem eyes and trabeculectomy specimens of primary open angle glaucoma (POAG) were used in this study. The tissues were embedded in Lowicryl K4M and sectioned for electron microscopy. Then the sections were subjected to protein A gold immunohistochemical staining to determine the localization of elastin in the tissues. The sections were exposed to varying concentrations of PPE or alpha 1A EL, before immunolabeling, to evaluate the density of the gold particles in the tissue. The gold particles were localized in the elastic fibers of normal and POAG specimens. The density of gold particles was reduced by relatively low concentrations of PPE and alpha 1A-EL in both normal and POAG specimens. These results suggest that elastin is localized in the elastic fibers of human trabecular tissues, and relatively low concentrations of PPE or alpha 1A-EL dissolve the elastin in the tissues. PMID- 8213360 TI - [In vivo changes in epithelial cells following PEA using the lenses of albino rabbits]. AB - In this study, the changes in epithelial cells and the lens capsules of the eyes of albino rabbits which were subjected to phacoemulsification and aspiration (PEA) with or without intraocular lens (IOL) implantation were histopathologically evaluated. In the rabbits without implantation of IOLs, Soemmerring's ring was observed more frequently, and many fusiform cells reappeared in the junction between a section of the anterior lens capsule and the posterior lens capsule. Folding in the posterior lens capsule increased over time. When IOLs were implanted, the IOLs successfully inhibited Soemmerring's ring formation. However some lens fibers still proliferated between the IOL and lens capsule. Fusiform cell growth was observed adjacent to the anterior lens capsule, but cells did not extend across the lens surface. Epithelial cells were found to cover nearly the entire surface of the posterior capsule, causing opacity of capsule. These experiments indicated that after cataracts resulted from the proliferation of lens epithelial and fusiform cells, and folds induced by contraction. PMID- 8213361 TI - [The effect of hyaluronic acid on proliferation and differentiation of capillary endothelial cells]. AB - The effects of hyaluronic acid (HA) on capillary endothelial cells were studied in cell culture. The capillary endothelial cells were obtained from the bovine adrenal cortex. The proliferation of endothelial cells was inhibited by the addition of HA to the culture medium. Significant inhibition was observed consistently at concentrations of 100 micrograms/ml or greater. Capillary-like networks were formed by the differentiated endothelial cells in co-culture with rabbit corneal keratocytes and in type I collagen gels. They were inhibited by the addition of HA at a concentration of 200 micrograms/ml. The cell proliferation and differentiation were not significantly affected by different HA molecular weights. PMID- 8213362 TI - [An experimental and clinical study of chorioretinal photocoagulation using a frequency-doubled Nd: YAG laser]. AB - We developed a new frequency-doubled Nd: YAG laser system which works on 100 volts AC and emits continuous wave green laser light of 532 nm. Histological observation of rabbit eyes revealed no difference in chorioretinal lesions produced with the frequency-doubled Nd: YAG laser or with an argon green laser. This device was then clinically applied to 69 eyes of 59 patients with several disorders such as diabetic retinopathy, retinal vein occlusion, Eales' disease, Coats' disease, age-related macular degeneration, lattice degeneration in the peripheral retina, macular hole, and retinal tear. The ophthalmoscopic findings showed no visible differences in the lesions made with this device or with the argon laser. No complications were observed in these patients except for one case of central retinal vein occlusion, which developed vitreous hemorrhage after the treatment. This solid-state laser system has some mechanical advantages over the gas laser, i.e. reduced cooling requirements, easy maintenance, and long life, and it is considered to be usable clinically. PMID- 8213363 TI - [Fluorophotometric measurement of tear volume and tear turnover rate in human eyes]. AB - Tear volume and turnover rate were measured in 31 normal eyes using a newly designed objective fluorophotometer. After instillation of 1 microliter of 50,000 ng/ml fluorescein solution, its concentration in the lower marginal strip was measured every minute for 10 minutes after instillation. The tear volume and the tear turnover rate were determined using the method of Mishima et al. (Invest. Ophthalmol. Vis. Sci., 1966). The tear volume in this study was 12.4 +/- 6.2 microliters, initial turnover rate was 31.5 +/- 14.4%/min., and basal turnover rate was 24.0 +/- 14.2%/min. (Mean +/- SD). There were no significant differences in sex, age or use of contact lens. We also measured the tear volume and turnover rate using 5 microliters of 10,000 ng/ml fluorescein solution in the same way. The result turned out to be significantly higher, suggesting that minimal irritation is required for evaluating the tear flow. PMID- 8213364 TI - [Corneal endothelium damage by air bag system]. AB - We have reported in the past a car crash in which the air bag system might have caused driver's corneal endothelial cell loss. To evaluate the corneal endothelial cell loss caused by air bag systems, we performed several air bag impact tests. We found that the corneal endothelial cell loss was greater at a distance of 240 mm than other distances. We also found that the corneal endothelial cell loss caused by the air bag which has bigger inflater and heavier material was significantly greater than that caused by other systems. This study offers basic data to improve the safety of air bag systems. PMID- 8213365 TI - [Hepatitis C virus in the aqueous humor]. AB - Since a method for detecting hepatitis C virus (HCV) antibody has been established, many cases of non-A non-B sporadic and post-transfusion hepatitis are now known to have been caused by HCV. It is important to take steps against the nosocomial transmission of HCV as with the hepatitis B virus. Sera from patients in our ophthalmological clinic were tested for the presence of HCV antibody during the seven months from Oct. 1991 to Apr. 1992, utilizing C-100-3 antigen. We then searched for the presence of HCV in human aqueous humor among HCV antibody positive patients at the time of cataract surgery, utilizing the polymerase chain reaction (PCR) method. HCV antibody was found in 11 of 226 cases (4.9%); aqueous humor of six eyes from 5 of these cases tested with PCR showed negative results. PMID- 8213366 TI - [The long term results of hyperbaric oxygen treatment for macular edema with retinal vein occlusion]. AB - We retrospectively evaluated the effect of hyperbaric oxygen treatment on seventy nine eyes of seventy cases with cystoid macular edema secondary to retinal vein occlusion. Twenty-three eyes had central retinal vein occlusion (CRVO), and fifty six eyes had branch retinal vein occlusion (BRVO). Visual acuity improved by two lines or more in 40 eyes (17%) with BRVO, and in 10 eyes (44%) with CRVO immediately after the therapy. Six months or more after treatment, visual improvement persisted in 14 of 30 BRVO eyes (47%), and in only one of 11 CRVO eyes (9%). CRVO showed poor prognosis in the long term compared with BRVO. We speculated that activation of aerobic metabolism might be more important than reduction of vascular hyperpermeability as the therapeutic effect of hyperbaric oxygen, and that hyperbaric oxygen might mainly affect the retinal cells in the marginal zone of the ischemic retina in the macular region. PMID- 8213367 TI - [Posterior sub-Tenon's injections of repository corticosteroids in uveitis patients with cystoid macular edema]. AB - Repository corticosteroid was injected into the posterior sub-Tenon's space in 29 cases (39 eyes) of cystoid macular edema (CME) secondary to uveitis. They included 12 cases of Behcet's disease, 7 cases of Sarcoidosis, one case of tuberculous uveitis and 9 cases of etiology unknown uveitis. In some of the patients injections were repeated twice to seven times at intervals of more than 2 weeks. Twenty two of the 39 treated eyes (56.4%) showed visual improvement in at least two lines of visual acuity. Eleven eyes showed no improvement in vision. Most of them had already had bad visual acuity (0.2 or less) before the injections. Complications of the treatment included cataract in 6 eyes, glaucoma in one, and blepharoptosis in one. Injection of repository corticosteroids into the posterior sub-Tenon's space was effective in the treatment of CME secondary to uveitis. However, we have to beware of the complications of this treatment. PMID- 8213368 TI - [Sensory status on Bielschowsky head tilt test]. AB - The purpose of this work was to confirm ocular deviation during head tilt in cases of superior oblique muscle palsy. Ocular vertical deviation and cyclodeviation under head tilt loading were examined in nine cases with superior oblique muscle palsy using a new device, celled a modified phase difference haploscope (M-PDH). The M-PDH is able to measure a quantitative head tilt loading towards both sides. Tests using the M-PDH revealed the difference in angle of head tilt at the onset of hyperdrift and the degree of vertical deviation during head tilt towards the paretic side. Among the cases of superior oblique muscle palsy tested, ocular vertical deviation was classified into three types depending on the angle of head tilt. PMID- 8213369 TI - [Retinal whitening following vitrectomy for epiretinal macular membrane]. AB - To investigate the clinical pictures of retinal whitening following epiretinal membrane dissection. I studied retrospectively the records of 18 eyes which had undergone vitrectomy. Two types of retinal whitening were observed: cotton wool like spots within the superficial retinal layers and a linear or dendritic pattern within the deep retinal layers. The spots were mainly noted in idiopathic cases and resolved completely in a few weeks, and the pattern was observed in macular pucker cases after retinal detachment surgery and persisted for a long time after vitrectomy. PMID- 8213370 TI - Circadian rhythms of urinary saturation levels of calcium oxalate and calcium phosphate in normal male individuals. AB - The circadian rhythms of the calcium oxalate, calcium phosphate, and brushite saturation levels as estimated by the AP(CaOx), AP(CaP), and AP(Bru) indices (Tiselius), respectively, were studied in 5 healthy males on three different occasions. These indices were calculated from the data of urinary specimens collected in 2.5-hour fractions except during sleep. The calcium oxalate and brushite saturation levels peaked between 5:30 and 8:00 am, and these were significantly higher than in the other periods. The calcium phosphate saturation level had two peaks that occurred between 8:00 and 10:30 am and between 1:00 and 6:00 pm. The ion-activity products of octacalcium phosphate and hydroxyapatite, calculated from the AP(CaP) index, exhibited a pattern similar to the AP(CaP) values, indicating a high risk of crystallization for both substances at around the same peak periods. In conclusion, early morning was found to be the high risk period for calcium oxalate and brushite crystallization, while two high risk periods for octacalcium phosphate and hydroxyapatite were detected between 8:00 and 10:30 am and between 1:00 and 6:00 pm. PMID- 8213371 TI - [Clinical studies on the need of prophylactic antibiotics during extracorporeal shock wave lithotripsy]. AB - We examined whether prophylactic antibiotics are necessary or not during the ESWL treatment for patients with urolithiasis. Twenty-eight patients with unilateral renal or ureteral stones composed of calcium oxalate, calcium phosphate or the mixed stones were treated with MPL 9000 between May 12 and September 30, 1992. Although 17 patients (60.7%) had complications of pyuria before treatment, none of the 28 patients had taken any prophylactic antibiotics during the treatment. To evaluate the clinical signs of infection, we examined the white blood cell count, in blood and urine sediment and serum C-reactive protein (CRP) value at the time of 1, 3 and 7 days after ESWL treatment, and body temperature and urine culture at the time immediately after the treatment in addition to the above mentioned days, compared with the pre-treatment data. White blood cell count at one day after ESWL treatment was significantly elevated both in the patients with and without pyuria, while body temperature at the time immediately after the treatment was significantly elevated only in the patients with pyuria. Six of the 23 patients (26.1%) with preoperative sterile urine and who had urine culture immediately after ESWL, had bacteriuria. However, none of the 28 patients had any clinically significant infectious complications during ESWL treatment without any antibiotics therapy. We concluded that it is important to examine urine culture immediately after ESWL treatment for early protection from complication of urinary tract infection and that administration of prophylactic antibiotics is not necessary during ESWL treatment for patients with non-infection stones even concomitantly with pyuria. PMID- 8213372 TI - [Clinical effects of transabdominal simple hysterectomy on micturition function]. AB - We prospectively investigated micturition function in 68 women who were operated on by transabdominal simple hysterectomy for uterine myoma. Twelve parameters including stress urinary incontinence, obstructive symptoms, irritative symptoms, uroflow curves and amount of residue were subjectively or objectively evaluated before surgery and a mean of 4.4 months post-operatively. Though 55 patients (81%) had had one or more symptoms of micturition disorders prior to operation, surgery significantly reduced this number to 32 (47%) (p < 0.01). Hysterectomy significantly decreased the number of patients suffering from stress urinary incontinence, weak urinary stream, straining micturition, interrupted stream, urgency and frequency in the daytime. The relationship between the weight of the uterus removed and pre-operative symptoms of micturition disorders was assessed. Interrupted stream was present significantly more in the patients with a uterus weighing less than 400 grams and urgency in the patients with a uterus weighing more than 401 grams. We conclude that transabdominal simple hysterectomy is of use to improve micturition disorders pre-operatively recognized. PMID- 8213373 TI - [A clinical study of lomefloxacin on the patients with urinary tract infections- focused on lomefloxacin-induced photosensitivity reaction]. AB - Between April and October 1990, photosensitivity reactions were observed in 19 out of 338 patients who were administered lomefloxacin (LFLX) for the treatment of urinary tract infections (UTI) in our hospital. To certify the effectiveness and safety of LFLX to UTI, we carried out a controlled study with fixed dosages and durations. Patients with acute uncomplicated UTI and chronic complicated UTI were enrolled and LFLX dosages of 200 mg b.i.d. for 7 days and 14 days, respectively, were administered. The overall efficacy rates were 100% and 84% respectively. Concerning the bacteriological effect, Escherichia coli and Klebsiella pneumoniae were eliminated in every case, while 3 strains of Enterococcus faecalis 2 strains of Pseudomonas aeruginosa and one strain of Enterobacter cloacae persisted. No photosensitivity reaction or noteworthy severe adverse reactions were observed among 200 cases enrolled in this study of restricted dosages and durations. We, urologists, need to be well-informed about photosensitivity reactions induced by quinolone antimicrobial agents. LFLX was proven to be effective in UTI without showing any photosensitivity reactions when administered by our fixed dosages and durations. PMID- 8213374 TI - [Age-related changes in the size and shape of the prostate observed by transrectal ultrasonography]. AB - To elucidate the change with aging in prostatic morphology, 447 cases without acute diseases and prostate cancer of the first visit from January 1988 to December 1990 were examined by transrectal ultrasonography. Total weight of the prostate, area of maximum section, lateral and anteroposterior diameter on the maximum section and supero-inferior diameter were evaluated. The total weight of the prostate was not found to be correlated with aging. The total weight of the prostate showed a high variation with aging. Prostate growth with more than 30 g was greater in the fifties and increased gradually thereafter. Similar findings were observed for antero-posterior diameter on the maximum section and supero inferior diameter. With aging, the total weight of the prostate in 20-30% of the patients showed an increase while in 30-40% of the patients, no increase. The total weight of the prostate increased in the fifties with subsequent gradual increase in the sixties. According to prostate shape, antero-posterior diameter on the maximum section and supero-inferior diameter was related to the weight of the prostate. PMID- 8213375 TI - [Chlamydia trachomatis infection in young men with acute epididymitis and their sexual partners]. AB - Untreated infection of female partners by men with chlamydial epididymitis may have serious effects on the partners' fertility. To assess the need for detailed microbiological investigation, 32 patients, 35 years old or younger, with epididymitis and their sexual partners were examined. The patients underwent thorough evaluations, including chlamydia isolation, microscopy of urethral swab, bacterial culture, and chlamydia serologic testing. An infective cause was identified in 56% of the patients. The most common microorganism was Chlamydia trachomatis. This microorganism was identified from urethral swabs in 11 patients (34%). A total of 18 sexual partners were traced and investigated for chlamydia antigen by cervical swab, urinary bacterial culture, and chlamydia serologic testing. Of the 18 female sexual partners screened, 9 were partners of patients with chlamydial epididymitis; 78% of these women had the same infection. Young men with epididymitis, as well as their partners, should undergo full microbiological evaluation including Chlamydia trachomatis for adequate treatment of this infection. PMID- 8213376 TI - [Congenital arteriovenous malformation of the kidney: report of two cases- detection by digital subtraction angiography with carbon dioxide]. AB - Two cases of arteriovenous malformation of the kidney were reported. The first case was a 19-year-old female, complaining of right flank pain and gross hematuria. Right selective renal arteriography revealed a 2 x 1.5 cm large cisoid type arteriovenous malformation at the most distal region of the lower branch of the renal artery. Transcatheter embolization, using Gelfoam and absolute ethanol, was successfully done, which was confirmed with repeated digital subtraction angiography with carbon dioxide (CO2-DSA). The second patient was a 55-year-old female with past history of right idiopathic renal bleeding, complaining of right flank colicky pain and gross hematuria. Right selective renal arteriography was done without any pathological findings, while CO2-DSA documented an arteriovenous malformation in the hilar region. Transcatheter embolization was not done, because the malformation seemed to be proximally located. Thus CO2-DSA was thought to be a reliable method in the diagnosis of arteriovenous fistula. PMID- 8213377 TI - [Fat necrosis arising in the perinerhrium]. AB - The patient was a 74-year-old woman. During the investigation for abdominal pain, a mass lesion was detected adjacent to the left kidney using ultrasound. The left radical nephrectomy was performed under a clinical diagnosis of liposarcoma. Histological examination revealed fat necrosis with hemorrhage arising in the perinephrium. No tumor cells were confirmed microscopically. We reviewed the literature, but there found, no case reports of fat necrosis arising in the perinephrium, except for reports in rats or cows. PMID- 8213379 TI - [A case of infected renal cyst: the usefulness of magnetic resonance imaging for preoperative diagnosis]. AB - A 22-year-old woman was admitted to our hospital with complaints of fever and left flank and back pain. Laboratory examinations showed leukocytosis and high C reactive protein level. On the upper pole of the left kidney, two renal cysts were disclosed by ultrasonography and computerized tomography. A simple renal cyst and an infected renal cyst could be distinguished by magnetic resonance images (MRI), because the infected renal cyst was less intense than the simple renal cyst on T2 weighted MRI. Percutaneous puncture and drainage of the cyst were performed under the guidance of ultrasonography. Bacterial culture of the infected cyst fluid was positive for E. coli. Two months after treatment, computerized tomography showed no evidence of recurrence of the infected renal cyst. PMID- 8213378 TI - [Renal or perirenal malignant lymphoma: report of three cases]. AB - We report three cases of renal or perirenal malignant lymphoma. The patients were a 69-year-old woman presenting with lumbago, a 43-year-old man with fever and erythema, and a 69-year-old woman with general malaise. In each case, renal or perirenal tumor was discovered by abdominal ultrasound. Biopsy and microscopic examination revealed the diagnosis of non-Hodgkin's malignant lymphoma. The computerized tomography patterns of the cases were different from each other; "direct invasion" in the first case, "solitary nodule" in the second case, and "engulfment" in the third case. Chemotherapy and/or radiation therapy were performed. Only the third case is still alive at present. The computerized tomography pattern of renal or perirenal malignant lymphoma was classified into five groups; I) multiple nodules, II) solitary nodule, III) engulfment, IV) direct invasion, V) diffuse infiltration. This classification should be useful in making an accurate and early diagnosis. PMID- 8213380 TI - [A case of blind-ending bifid ureter--review of 114 cases reported in Japan]. AB - A 45-year-old man was admitted to our hospital with a 3-month history of pain on micturition and a residual sensation. Intravenous pyelography demonstrated a duplication of the right ureter with one segment ending blind, measuring 2.0 cm in length and 0.4 cm in diameter. On CT scan of the abdomen, there was no evidence of an ectopic kidney at the distal end of the blind-ending branch. There have been 114 cases of blind-ending bifid ureter reported in Japan, including our own. Clinical aspects are statistically analyzed. PMID- 8213382 TI - A case of prostate cancer with a large abdominal mass effectively treated with a high dose of diethylstilbestrol-diphosphate. AB - A case is reported about a 75-year-old man with a large abdominal lymph node metastasis caused by prostate cancer effectively treated by a high dose of diethylstilbestrol-diphosphate. The usefulness of diethylstilbestrol-diphosphate for prostate cancer patients with lymph node metastasis is emphasized. PMID- 8213381 TI - [A case of metastatic urinary bladder tumor from colon carcinoma]. AB - A 62-year-old female patient underwent an operation for a brain tumor. The pathological diagnosis of the resected specimen was metastatic adenocarcinoma with signet-ring cells. The primary lesion was found in the ascending colon. In addition, a non-papillary and pedunculated tumor was found on the right wall of the bladder on cystoscopy. Biopsy of the bladder tumor showed adenocarcinoma with signet-ring cells, which was the same as the histologies of the colon and the brain tumors. Under the diagnosis of metastatic bladder tumor, transurethral resection of the tumor was performed. This is the first case of metastatic bladder carcinoma from the colon reported in Japan. PMID- 8213383 TI - [Rectal involvement by prostate carcinoma: a report of three cases]. AB - We reported 3 cases of rectal involvement by locally invasive prostate carcinoma which caused an urethrorectal fistula in case 1 and a rectal stenosis in case 2 and 3. Discriminating between primary rectal carcinoma and prostate carcinoma locally invasive to the rectum is very important because of distinct differences in treatment and prognosis. To confirm the tumor origin, tumor markers, proctosigmoidscopy, computerized tomography and biopsy with immunohistochemical staining for prostate specific antigen were useful. PMID- 8213385 TI - [A case of ectopic vas deferens with a chief complaint of male sterility]. AB - A case of ectopic vas deferens in a 40-year-old male was reported. He visited our clinic with a complaint of male sterility for the past 10 years. Urological examinations revealed azoospermia, right renal aplasia and the ectopic insertion of right vas deferens into the right lower ureter with a blind-ending ureterocele. Bilateral testicular histological studies showed normal spermatogenesis in right testis and no spermatogenesis in left one. A vasovasostomy was performed. Sperm were seen in the semen 3 weeks after the operation. Including this patient, 54 cases (74 ectopic vas deferens) have been reported in the literature to date. The characteristics of age, subjective complaints, accompanied anomalies, diagnosis, treatment and the embryology are discussed. PMID- 8213384 TI - [Urethral condyloma acuminatum with severe dysplasia in a male patient detected human papillomavirus type 11: a case report]. AB - We report a case of urethral condyloma acuminatum with severe dysplasia detected human papillomavirus (HPV) type 11. A 47-year-old male patient visited St. Luke's International Hospital complaining of tumor at the urethral meatus. One small papillary lesion was found and excised. Histopathological examination revealed condyloma acuminatum with severe dysplasia. Immunohistochemical detection for HPV antigen in the specimen of condyloma acuminatum was positive and that of severe dysplasia was negative. In an electron microscopical study, viral particles were demonstrated only in the specimen of condyloma acuminatum. Detection of HPV DNA was performed using in situ hybridization (ISH) and southern blot hybridization (SBH). HPV type 11 was found in both lesions. In conclusion, although previous studies have shown that HPV type 16/18 was especially correlated with genital severe dysplasia and carcinoma, the process of malignant transformation was suggested in the association with HPV type 11. PMID- 8213386 TI - Paratesticular leiomyosarcoma with elevated serum basic fetoprotein: a case report. AB - A case of paratesticular leiomyosarcoma associated with elevated serum basic fetoprotein level is reported. A 45-year-old male visited our hospital with a 6 month history of a painless left scrotal mass. High orchiectomy was performed under the diagnosis of left testicular tumor. Macroscopic and microscopic examination of the resected tumor demonstrated it to be paratesticular leiomyosarcoma. The value of serum basic fetoprotein, which is a newly identified oncofetal protein and useful as a tumor marker in some kinds of malignant neoplasm, was elevated before therapy, and its fluctuation was correlated with his clinical course. In spite of chemotherapy and resection of metastatic lesions in the lung, his condition gradually deteriorate with increasing serum basic fetoprotein level, and he died with carcinomatosis 2 years and 6 months after his admission. We suggest that basic fetoprotein is a useful tumor marker in this disease. PMID- 8213387 TI - [A case of malignant mesothelioma of the tunica vaginalis testis]. AB - A case of malignant mesothelioma of tunica vaginalis testis experienced in an 83 year-old male who presented with a complaint of left intrascrotal pain is reported. The tentative diagnosis was acute epididymitis. Left epididymectomy was performed following the unsuccessful treatment with antibiotics. The histology of the surgical specimen revealed malignant mesothelioma. Radical excision of the left spermatic cord and scrotal content indicated locally advanced disease with positive surgical margin. Metastatic workup, including abdominal and chest computerized tomography scan, magnetic resonance imaging and bone scan demonstrated presence of metastasis to the paraaortic lymph nodes and the lumber spine. The patient is being followed conservatively in consideration of his age and advanced stage of the disease. PMID- 8213388 TI - [Statistics of the operation at Division of Urology, Shimada Municipal Hospital: 1987-1991]. PMID- 8213389 TI - Total inclusion/zero reject models in general education. Implications for deaf children. PMID- 8213390 TI - Characteristics of effective teachers. AB - We designed and administered rating and ranking instruments to examine the perceptions about teaching characteristics held by administrators, academic department chairpersons responsible for evaluating teaching, instructional faculty, and deaf college students. The differences in perceptions found between supervisors and teachers about characteristics of effective teaching indicate a need for ongoing dialogue. In addition, teachers and deaf college students were found to differ in their views of the importance of certain characteristics, and we suggest teachers discuss these perceptions with students. We also recommend additional research on particular characteristics of effective teaching. PMID- 8213391 TI - Demographic and audiological profiles of deaf children in Texas with cochlear implants. AB - This paper reports the findings of a study that examined the demographic, educational, and audiological characteristics of a sample of children in Texas who had received cochlear implants. Children who had received implants and children who had not were compared. Differences between the two groups are discussed in the context of the criteria that have been published in the literature for selecting implant candidates. Results indicate that although the published selection criteria were predictive of the characteristics of the implanted sample, there was a degree of flexibility in applying the criteria to choose implant recipients. Audiological comparisons revealed that cochlear implant recipients experience greater reductions in average hearing thresholds than do users of conventional aids, although these findings should be viewed as preliminary. PMID- 8213392 TI - A national survey of school psychological services for deaf and hard of hearing students. AB - The survey reported on in this paper replicated and modified Levine's (1974) nationwide survey of the psychological services provided for deaf and hard of hearing students. The purpose of our survey was to up date the information in light of the requirements of PL 94-142 (1975) and current practice. We noted several changes in practice since the first survey, but unfortunately, little change has taken place in many important areas. We suggest possible areas for expanding the role of school psychologists and discuss implications for training. PMID- 8213393 TI - The expressive communication of hearing mothers and deaf infants. AB - This paper describes the expressive communication and language of seven hearing mothers and their deaf infants. Severe-profound or profound bilateral sensorineural hearing loss was identified in the infants by 7 months of age; intervention programs emphasizing use of signing systems plus speech were started before 9 months of age. Communication behaviors during free play were observed when the infants were 12 and 18 months old. The frequency of the mothers' signing at 12 and 18 months was significantly correlated: mothers' patterns of frequent or infrequent signing were evident within several months of their infants' entry into programming. Mothers who signed most frequently reported that other adults (father and other relatives, friends) were also learning and using signs. Frequency of sign production by the infants at 18 months correlated significantly with frequency of sign production by the mothers when the infants were 12 and 18 months. The mothers' reports of their typical frequency of signing and of the sign lexicon size of their infants failed to correlate significantly with observed performance. PMID- 8213394 TI - Factors that contribute to stress as reported by teachers of deaf students at residential schools. AB - Many teachers of deaf students report that they experience high levels of stress related to their work. In this paper, we report the results of research implemented to search for different responses to items possibly indicative of stress, as reported by residential school teachers who follow two different communication philosophies: an oral approach and the Total Communication approach. Data were collected using a survey instrument developed by the researchers in this study, which was completed by 31 teachers following an oral approach and 93 following the Total Communication approach. Teachers also completed a second, standardized instrument. Results indicated that the two groups did not differ significantly in their total responses to the instrument developed by the researchers in the present study. However, they did differ on 2 of 10 possible stress factors: institutional provision of technical and personnel assistance and agreement with communication methodology. Future directions for research are included. PMID- 8213395 TI - Recall of English function words and inflections by skilled and average deaf readers. AB - This study examined whether skilled deaf readers sustain a more complete memory trace of English function words and inflections compared to average deaf readers and whether this is related to processing that has a phonological component. The superior accuracy of skilled readers on a verbatim recall task indicated that they are more able than average deaf readers to sustain a record of English function words and inflections. Elevations in processing time under the recall versus a comprehension condition were highly correlated with recall accuracy. On a separate task, the relative speed of skilled readers when making lexical decisions about phonologically similar word pairs indicated greater access to phonological information during word reading. However, the phonological facilitation measure did not correlate highly with recall accuracy nor increments in processing under the recall condition. PMID- 8213396 TI - Parental expectations as a factor in evaluating children for the multichannel cochlear implant. AB - Recent developments in technology have resulted in a new assistive device for profoundly deaf children: the cochlear implant. However, many variables must be considered when evaluating children for the device, one of which is parental expectations. Because expectations are sometimes unreasonable high, cochlear implant teams need to be aware of the dynamics involved in expectations and of ways to help parents come to a realistic understanding of the benefits and limitations of implants. PMID- 8213397 TI - Getting there. Update on recommendations by the Commission on Education of the Deaf. AB - Major progress on the recommendations of the Commission on Education of the Deaf was made by the Education of the Deaf Act Amendments of 1992 (PL 102-421); the Rehabilitation Act Amendments of 1992 (PL 102-569); and a U.S. Department of Education "Notice of Policy Guidance" clarifying its views on the commission's recommendations about elementary and secondary education. The changes, taken together, brought implementation of commission recommendations almost to closure. They also represented significant steps forward on behalf of deaf children, youth, and adults, setting the stage for further progress. PMID- 8213398 TI - Better compliance: physicians making it happen. PMID- 8213399 TI - Oxidized LDL, atherogenesis and antioxidants. PMID- 8213400 TI - Family-centered birthing: a style of obstetrics for family physicians. PMID- 8213401 TI - Domestic violence. PMID- 8213402 TI - Marked variability in methanol toxicity. PMID- 8213403 TI - Treatment approaches for urinary incontinence. PMID- 8213404 TI - 'Overtraining' in athletes and decreased libido. PMID- 8213405 TI - Family physicians and adolescent medicine certification. PMID- 8213406 TI - Diary from a week in practice. PMID- 8213407 TI - Cholelithiasis: current treatment options. AB - Up to 20 percent of the U.S. population may have cholelithiasis, but most of these persons remain asymptomatic. If symptoms or complications develop, several potential management strategies may be used. Open and laparoscopic cholecystectomy are definitive surgical treatments. Nondefinitive methods, such as lithotripsy, indirect dissolution, direct dissolution, sphincterotomy and drainage, have lower success rates but may be indicated in specific cases. Although laparoscopic cholecystectomy is a relatively new technique, its morbidity and mortality rates are comparable to those of open cholecystectomy, and it tends to be less expensive than other surgical methods. For these reasons, laparoscopic cholecystectomy is rapidly becoming the surgical method of choice in the treatment of cholelithiasis. PMID- 8213408 TI - Contact dermatitis and urticaria from environmental exposures. Agency for Toxic Substances and Disease Registry. AB - Dermatitis accounts for about 30 percent of all illnesses in the workplace. A thorough exposure history is the most important element in accurate diagnosis of skin lesions. In certain cases, skin lesions may be valuable diagnostic clues to the presence of systemic toxicity. Irritant and allergic contact dermatitis, photosensitivity contact dermatitis, and contact urticaria are examples of skin lesions that may be caused by exposure to an environmental agent. PMID- 8213409 TI - Bronchial carcinoid presenting as refractory asthma. AB - Bronchial carcinoids are low-grade malignant neoplasms that usually occur in the central airways. The central endobronchial location typically results in symptoms of bronchial obstruction. Infrequently, asthma-like symptoms may be produced by endobronchial tumors. The diagnosis of bronchial carcinoid is often made after months of unsuccessful treatment for more common respiratory conditions. PMID- 8213410 TI - Traveler's diarrhea. AB - Traveler's diarrhea is the most common health problem in persons who visit developing countries. Dietary precautions are the mainstay of prevention. Since bacteria are responsible for 50 to 80 percent of cases of traveler's diarrhea, antibiotics are the drugs of choice for empiric therapy. Because bacteria are becoming increasingly resistant to trimethoprim-sulfamethoxazole and doxycycline, newer antibiotics, especially the fluoroquinolones, should be considered as first line therapy. Antimotility agents may help reduce symptoms, but they should not be given to patients who have fever or bloody diarrhea. Antibiotic prophylaxis is recommended for certain high-risk individuals. PMID- 8213411 TI - The aseptic meningitis syndrome. AB - The diagnosis and treatment of acute meningitis is a challenge for the primary care physician. Differentiating between bacterial meningitis and aseptic meningitis is not always straightforward. The aseptic meningitis syndrome is usually viral in origin, and enteroviruses account for most cases. The aseptic syndrome also may be caused by unusual bacterial organisms such as Mycobacterium tuberculosis, Leptospira species, Brucella species, Borrelia burgdorferi and others. The classic presentation consists of the acute onset of meningismus, headache, fever, malaise with pleocytosis and normal glucose and slightly elevated protein in the cerebrospinal fluid. Cerebrospinal fluid lactate and serum C-reactive protein measurements may be helpful in differentiating aseptic meningitis from treatable bacterial meningitis. Aseptic meningitis of viral origin usually responds to expectant care. Other causes of aseptic meningitis must be searched for and treated if present. PMID- 8213412 TI - Ovarian mucinous cystadenoma: evaluating the pelvic mass. AB - An ovarian mucinous cystadenoma does not cause symptoms until it becomes very large. In women who present with nonspecific abdominal complaints, a pelvic examination must be performed and a high index of suspicion for pelvic pathology must be maintained. Mucinous cystadenomas are benign, allowing a conservative approach to treatment, especially in young patients who wish to maintain fertility. PMID- 8213413 TI - Managing the Foley catheter. AB - Urethral catheterization of the bladder is a commonly performed but potentially hazardous procedure. With proper patient preparation and catheter selection, difficult catheterizations can be accomplished without injuring the patient. Complications of catheterization include infection, injury to the urethra or bladder, and catheter malfunction. Physician supervision of catheter care is essential. Most of all, prompt replacement of the urethral catheter with an alternative method of bladder drainage, such as spontaneous voiding, external condom catheterization, clean intermittent catheterization or, possibly, suprapubic catheterization, is the best way to prevent the complications of urethral catheterization. PMID- 8213414 TI - Outpatient management of chronic bronchitis in the elderly. AB - Chronic bronchitis, one of the principal manifestations of obstructive lung disease, causes significant morbidity, especially among older patients. The "blue bloater" type of clinical presentation arises from hypoxemia and is characterized by breathlessness and functional impairments of communication and mobility. Acute infectious episodes often respond to antibiotic therapy, but the underlying problems of impaired airway immune responsiveness and hypersecretions cause chronic symptoms in many patients. Long-term management strategies are directed at optimizing immune defenses, improving airway patency through the use of anticholinergic and bronchodilating medications, correcting hypoxemia, providing supportive nutritional care and instituting measures to maximize the function of respiratory musculature. PMID- 8213415 TI - ACE inhibitors: review of four new agents. AB - Angiotensin converting enzyme inhibitors are effective in the treatment of hypertension and congestive heart failure. Within the past two years, four new agents in this class-benazepril, fosinopril, quinapril and ramipril--have been approved in the United States for use in the treatment of hypertension. These agents have been shown to be as effective as the older angiotensin converting enzyme inhibitors in treating hypertension and, in limited trials, congestive heart failure. The side effect profiles of the new agents are similar to those of other agents in this class that do not contain a sulfhydryl group. Fosinopril has a unique route of elimination that may make it the preferred agent in patients with renal failure. Otherwise, the new angiotensin converting enzyme inhibitors have no proven clinical advantages over other available agents. However, at moderate to high doses, the new agents may be substantially less expensive. PMID- 8213416 TI - U.S. Preventive Services Task Force releases policy statement on home uterine activity monitoring. PMID- 8213417 TI - Recommendations issued for patients infected with HTLV type I or II. Centers for Disease Control and Prevention and a U.S. Public Health Service working group. PMID- 8213418 TI - Unusual case of total pulsus alternans that resulted from varying afterload caused by a subclavian artery rupture. PMID- 8213419 TI - Pulmonary infundibular stenosis, coronary artery disease, and aortic regurgitation caused by mediastinal radiation. PMID- 8213420 TI - Massive chylopericardium due to congenital fistulas. PMID- 8213421 TI - Intermittent regurgitation flow with Bjork-Shiley mitral prosthesis in atrial fibrillation. PMID- 8213422 TI - Torsades de pointes with Almokalant, a new class III antiarrhythmic drug. PMID- 8213423 TI - Transesophageal echocardiography in patients with heparin-induced thrombocytopenia and thrombosis. PMID- 8213424 TI - Superior vena cava syndrome after repeated insertion of transvenous pacemaker. PMID- 8213425 TI - Bepridil-induced pulmonary fibrosis. PMID- 8213426 TI - Hematologic complications of diltiazem overdose. PMID- 8213427 TI - Magnesium restores the altered force-frequency relationship in failing human myocardium. PMID- 8213428 TI - The effect of cardioversion on exercise capacity in patients with atrial fibrillation. PMID- 8213429 TI - Characterization of the aortic echo-Doppler profile in normal children during maximal treadmill exercise. PMID- 8213430 TI - Epicardial lipoma. PMID- 8213431 TI - Negative air-contrast test does not exclude the presence of patent foramen ovale by transesophageal echocardiography. PMID- 8213432 TI - Selective presaturation magnetic resonance angiography: new method for detecting intracardiac shunts. PMID- 8213433 TI - Interposed abdominal compression-cardiopulmonary resuscitation: are we missing the mark in clinical trials? PMID- 8213434 TI - Epidemiology of heart failure in the United States. PMID- 8213435 TI - Prediction of sudden cardiac arrest: risk stratification by anatomic substrate. AB - The prognostic importance of coronary artery anatomy to specific outcomes including ventricular tachycardia/fibrillation was evaluated in 372 consecutive patients undergoing cardiac catheterization at University Hospital at Stony Brook between 1981 and 1984. The hypothesis that proximal left anterior descending artery narrowing before the first septal perforator had a specific relationship to survival was again tested in this cohort. The population was prospectively followed for 8 years, with all clinical management decisions made independently by the patient's primary or referring physician. Multivariate statistical and life table analyses were performed after comprehensive follow-up. Significant narrowing in the proximal left anterior descending artery was associated with an increased risk of sudden cardiac death (p = 0.0002). Abnormalities of contractility in the diaphragmatic segment of the left ventricle in addition to an elevation of the left ventricular end-diastolic pressure and the presence of congestive heart failure (p < 0.05) were other contributory variables. Outcome in patients with proximal left anterior descending coronary artery disease who underwent aortocoronary artery bypass to the artery demonstrated improved survival (p < 0.05). Risk stratification of patients at high risk for sudden cardiac death is possible and may allow identification for an aggressive approach or interventional trials. PMID- 8213436 TI - Potential impact of pulmonary artery catheter placement on short-term management decisions in the medical intensive care unit. AB - The purpose of this study was to examine the potential impact of pulmonary artery (PA) catheter placement on short-term management decisions in the medical intensive care unit (ICU). One hundred three patients were examined over an 18 month period. The predominant indications for PA-catheter placement included refractory congestive heart failure, airspace disease, uncertain cardiac filling pressures, or hypotension. In 58 (56%) of the 103 patients, management recommendations changed as a direct result of knowledge gained by PA catheter placement. These changes involved fluid therapy recommendations in 41 patients, vasopressor use in 17 patients, intravenous vasodilator use in 24 patients, and recommendations for the use of inotropic agents in 15 patients. Although 18 patients experienced early or late complications, major events were limited to a single pneumothorax requiring chest tube insertion and four episodes of bacteremia. No deaths were directly attributable to the catheter insertion. In critically ill patients in the medical intensive care unit, PA-catheter placement leads to changes in recommendations for management in a substantial portion of patients with little risk of life-threatening complications in those who receive such invasive monitoring. PMID- 8213438 TI - Importance of ischemic preconditioning and collateral circulation for left ventricular functional recovery in patients with successful intracoronary thrombolysis for acute myocardial infarction. AB - We studied the effects of myocardial ischemic preconditioning and preexistent collateral circulation on the preservation of left ventricular function in 30 patients who had successful intracoronary thrombolysis within 6 hours after the onset of a first acute anterior myocardial infarction. The existence of ischemic preconditioning was defined as the episode of recurrent ischemic chest pain within 4 hours before the onset of acute myocardial infarction. In 16 patients with ischemic preconditioning (group A), the left ventricular ejection fraction during the convalescence of myocardial infarction was 57% +/- 11% (mean +/- SD); regional wall motion in the infarct area was 13% +/- 9%. In 14 patients without ischemic preconditioning (group B), the left ventricular ejection fraction and regional wall motion in the infarct area were 46% +/- 9% and 5% +/- 9% (both p < 0.05 vs group A). Moreover, among group A patients, seven patients having a well developed collateral circulation during the acute stage of myocardial infarction showed a more prominent improvement in regional wall motion in the infarct area compared with nine patients having poor or no collateral circulation (18% +/- 8% vs 9% +/- 7%, p < 0.05). These data indicate that ischemic preconditioning is effective for the preservation of left ventricular function in patients with successful intracoronary thrombolysis and that preexistent coronary collateral circulation potentiates this favorable effect of ischemic preconditioning. PMID- 8213437 TI - Noninvasive detection of reperfusion after thrombolysis based on serum creatine kinase MB changes and clinical variables. TAMI 7 Study Group. Thrombolysis and Angioplasty in Myocardial Infarction. AB - Coronary artery patency after thrombolytic therapy has important prognostic implications for survival after acute myocardial infarction. The ability to noninvasively identify patients early after thrombolysis may therefore allow other strategies, such as adjunctive therapy or rescue angioplasty, to be used to restore patency of the infarct-related artery. This study examined the use of a rapid creatine kinase (CK)-MB assay in conjunction with selected clinical variables for noninvasive detection of reperfusion after thrombolysis. Patients were enrolled in a study evaluating accelerated plasminogen activator dose regimens with patency assessments by first angiographic injection during acute angiography at a median and interquartile range (25th and 75th percentiles) 142 (96,195) minutes after starting thrombolytic therapy. Serum CK-MB samples measured by a rapid dual monoclonal antibody assay were obtained in 207 patients before (baseline) and 30 minutes, 90 minutes, and 3 hours after starting thrombolytic therapy. In 109 patients a CK-MB sample was obtained within 10 minutes of acute angiography (angio sample). At acute angiography the infarct related artery was patent (Thrombolysis in Myocardial Infarction trial grade 2 to 3 flow) in 71%. Baseline CK-MB values were similar in patients with and without later reperfusion at acute angiography: 3 (0,8) ng/ml and 0 (0,4) ng/ml, respectively. At acute angiography, patients with successful reperfusion had higher CK-MB values [46 (20,138) ng/ml] compared with patients with persistent occlusion of the infarct-related artery [8 (3,63) ng/ml; p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213439 TI - Sudden increase of the ST segment elevation at time of reperfusion predicts extensive infarcts in patients with intravenous thrombolysis. AB - Within 4 hours from the onset of symptoms in 61 patients with myocardial infarction and intravenous thrombolysis, ST segment elevation and creatine phosphokinase (CK) were measured every 15 minutes. Because of a premature enzyme rise, 42 patients (69%) were reperfused early (group 1). Immediately following reperfusion, eight of them (13%, group 1a) showed a marked increase of the ST elevation, in six of whom it was associated with clearly intensified chest pain. These patients exhibited a much steeper enzyme release and developed a larger enzymatic infarct size than patients (group 1b) without an additional transient ST elevation at reperfusion (CK peak 5.1 +/- 1.6 vs 9.8 +/- 4.2 hours after the start of thrombolysis; CK release 48 +/- 22 vs 19 +/- 18 IU/ml x hours, both p < 0.005). At angiography 11 days later, left ventricular function was significantly worse in group 1a than in group 1b (regional dyssynergic area 51 +/- 24 vs 21 +/- 18, global ejection fraction 39 +/- 14 vs 58 +/- 11; both p < 0.0005). During intravenous thrombolysis in acute myocardial infarction, some patients show a marked transient increase of the ST segment elevation at reperfusion. Their enzyme rise is very rapid and suggests a special reperfusion pattern. Most of these patients suffered large infarcts. PMID- 8213440 TI - High- and low-dose superoxide dismutase plus catalase does not reduce myocardial infarct size in a subhuman primate model. AB - Oxygen free radical scavengers have been found to decrease infarct size in dogs subjected to myocardial ischemia-reperfusion injury. A baboon open-chest model was used to determine if superoxide dismutase (SOD), an oxygen free radical scavenger, together with catalase would be equally effective in subhuman primates (baboons). The left anterior descending coronary artery (LAD) was ligated for 2 hours. Before reperfusion, the animals received the following: Group 1 (low-dose SOD/catalase; n = 5) received 15,000 IU/kg of SOD and 55,000 IU/kg of catalase IV over 1 hour, 15 minutes before reperfusion. Group 2 (high-dose human SOD [h SOD]/catalase; n = 5) received an intraatrial bolus of 400,000 IU of recombinant h-SOD and 27,500 IU/kg of catalase over 30 seconds, followed by 300,000 IU of h SOD and 55,000 IU/kg of catalase over 1 hour, beginning 15 seconds before reperfusion. Group 3 (n = 8) were control animals. Baboons were put to death 22 hours after reperfusion. Their hearts were excised and sectioned after the perfusion bed distal to the site of ligation was delineated with microvascular dye. The infarct zone was determined histologically. Areas of the perfusion bed and infarct zone were measured by planimetry. Infarct size did not differ significantly between the three groups: control, 66 +/- 7%; low-dose SOD/catalase, 68 +/- 5%; and high-dose h-SOD/catalase, 74 +/- 4%. In this model, high- and low-dose SOD with catalase did not result in any significant reduction in infarct size. PMID- 8213441 TI - Myocardial ischemia is not a prerequisite for the stimulation of coronary collateral development. AB - To understand better the temporal sequence of coronary collateral development and the factors that may govern that development, dogs were chronically instrumented with left circumflex (LCf) Doppler flow probe, ameroid constrictor, balloon occluder, and left atrial and aortic catheters. Collateral blood flow was measured at least weekly or when the coronary artery occluded. The reactive hyperemic response (RH) to a 15-second LCf occlusion was recorded three times per week. Most LCf arteries occluded during the 4th week after surgery. Two patterns of coronary collateral development were observed. In 11 animals collateral flow did not change for 2 or 3 weeks; peak RH and flow debt repayment, indexes of coronary vascular reserve, changed little. The next week there was an abrupt increase in collateral flow from approximately 15% of normal to 100%. This increase was coincident with a sudden loss of coronary vascular reserve and therefore suggests myocardial ischemia was the principal stimulus. However, in 11 dogs collateral flow increased gradually over 3 to 4 weeks as indexes of RH slowly decreased. The greatest increase in collateral flow occurred while peak RH was still approximately twice baseline flow, representing 80% of peak flow measured 1 week after surgery. Therefore in these animals ischemia is less likely to have been the major stimulus of coronary collateral development. PMID- 8213442 TI - Comparison of teboroxime and thallium for the reversibility of exercise-induced myocardial perfusion defects. AB - To determine the optimal technique for the scintigraphic detection of exercise induced myocardial perfusion defects, we compared teboroxime scanning to both stress/redistribution thallium imaging and the thallium reinjection method following exercise in 35 patients. The overall concordance for the presence of a perfusion defect between teboroxime and thallium scanning was 91% (p < 0.01) and 89% when teboroxime was compared with stress/reinjection thallium imaging (p < 0.01). More segments per scan with fixed defects were observed with redistribution imaging than with teboroxime or thallium reinjection (2.9 vs 2.0 vs 1.9; p < 0.02). Additionally, more transient defects were present with teboroxime than thallium, but less than with reinjection imaging. One half of the 52 fixed perfusion abnormalities on stress/redistribution thallium imaging demonstrated reversibility with both teboroxime imaging and thallium reinjection scanning, but less than 50% of these segments were concordant. Teboroxime allows for improved detection of reversible perfusion defects compared with stress/redistribution thallium scanning, but more ischemia is noted with thallium reinjection. The variation in the detection of segmental ischemic defects between teboroxime scintigraphy and thallium reinjection scanning probably reflects different physiologic properties and imaging protocols of these perfusion agents. PMID- 8213443 TI - Comparison of intimal thickening of Chinese and New Zealand coronary arteries. AB - Coronary arteries from forensic autopsies on 170 Chinese subjects aged 0 to 60 years were compared with those of 301 New Zealand individuals of corresponding ages to explore the reasons for the lower incidence of coronary artery disease in Chinese people. Intimal thickening progressed more rapidly in Chinese subjects up to the age of 30 years, but more slowly in the older age groups. The most striking difference was the much reduced lipid content of the intima and the better formed luminal surface of Chinese arteries of older subjects. These observations are consistent with the known dietary and plasma lipid differences between the peoples of China and the Western world, and they offer further evidence of the damaging effect of lipid and macrophages on the formation of an elastin membrane at the luminal surface of the intima subjacent to the endothelial cells. PMID- 8213444 TI - Histopathologic correlation of the three-layered intravascular ultrasound appearance of normal adult human muscular arteries. AB - The purpose of this study was to correlate intravascular ultrasound images from normal peripheral muscular arteries with the microscopic arterial components by using surgical microdissection techniques. There has been uncertainty about the precise anatomic constituents that are represented by the intravascular ultrasound three-layer image in human peripheral arteries. Forty of 66 grossly normal human femoropopliteal arterial segments obtained at autopsy were found to have a three-layered appearance and were subjected to selective surgical microdissection of intima, media, or adventitia. After microdissection, arteries were imaged with a 30 MHz intravascular ultrasound system; two observers blindly reviewed video tapes to assess for the presence or absence of a one-, two-, or three-layered arterial appearance. Removal of internal elastic lamina and/or intima results in a weak but evident inner ultrasound acoustic interface as a result of the media, which is normally echo-lucent. Removal of the adventitia and/or external elastic lamina results in a weak outer ultrasound acoustic interface. Isolated removal of the media does not alter the three-layered ultrasound image. In normal adult human femoropopliteal arteries the inner bright acoustic reflection (layer) is derived from the interface of blood with the intima and internal elastic lamina and the second bright interface (third layer) is from the external elastic lamina and adventitia. The mid-echo-lucent zone is the result of the media. However, any portion of the arterial wall, including muscular media, can act as an acoustic interface. PMID- 8213445 TI - Acute effects of captopril on the renal actions of furosemide in patients with chronic heart failure. AB - This study examined the effects of conventional doses of oral captopril on the renal responses to oral furosemide in ambulant patients with stable chronic heart failure. Twenty-five men (mean age 63 years) were randomized to one of two groups. Group 1 received placebo on days 1 and 2 before furosemide. Group 2 received placebo on day 1 before furosemide and captopril thereafter (i.e., captopril before furosemide on day 2). Urine was collected after either placebo or captopril and after furosemide (taken after placebo or captopril pretreatment). Captopril by itself did not affect renal function. Captopril did, however, significantly affect the renal response to furosemide. The increase in urine flow rate after furosemide in group 2 was decreased from 225% with placebo to 128% with captopril (p < 0.02). The increase in sodium excretion after furosemide was decreased from 623% with placebo to 242% with captopril (p < 0.001). Pretreatment with captopril abolished the increase in creatine clearance after furosemide. The increase in urinary albumin excretion (used as a marker of glomerular function) after furosemide was also significantly blunted by captopril. Conventional doses of captopril acutely inhibit the natriuretic and diuretic responses to furosemide at the glomerular level in ambulant patients with stable chronic heart failure. PMID- 8213446 TI - Abnormal cutaneous vasomotion and reduced cutaneous blood mass remain in congestive heart failure even with normalized cardiovascular hemodynamics. AB - To elucidate the pathophysiologic role of cutaneous microcirculation in congestive heart failure, finger cutaneous microcirculation was analyzed in 17 patients with acute heart failure (AHF) and 12 patients with hemodynamically compensated heart failure (c-HF) by using laser Doppler spectroscopy; the results were correlated with simultaneously obtained cardiovascular hemodynamics. Mean finger cutaneous blood flow in AHF was significantly lower compared with c-HF (p < 0.01) and control (n = 20, p < 0.001). Mean finger cutaneous blood mass was significantly reduced in both AHF (p < 0.01) and c-HF (p < 0.01) compared with control. Frequency of characteristic giant concave waves indicating sudden occurrence of flow reduction (B wave) was significantly higher in AHF (p < 0.01) and c-HF (p < 0.05) than that in control. Frequency of B waves correlated significantly with pulmonary capillary wedge pressure (PCWP) (r = 0.73, p < 0.01) and pulmonary artery systolic pressure (r = 0.54, p < 0.05). When changes after medical treatments were compared there were significant correlations between changes in B-wave frequency and changes in PCWP (r = 0.89, p < 0.01) and changes in finger cutaneous blood flow and changes in total systemic peripheral resistance (r = -0.75, p < 0.05). Cutaneous microcirculation in AHF was characterized by decreased finger cutaneous blood flow and finger cutaneous blood mass and prominent B waves, which reflected abnormal vasomotion activity. B-wave prominence and reduced finger cutaneous blood mass remained in c-HF even with normalized cardiovascular hemodynamics. PMID- 8213447 TI - Preoperative pulmonary hemodynamics and early mortality after orthotopic cardiac transplantation: the Pittsburgh experience. AB - The influence of preoperative transpulmonary pressure gradient (TPG) and pulmonary vascular resistance (PVR) on early post-transplant mortality was evaluated in 425 orthotopic transplant recipients. The overall 30-day post transplant mortality rate was 12.5%; the majority of the deaths (52.8%) were due to primary allograft failure. The 0- to 2-day mortality rate was threefold higher in patients with severe preoperative pulmonary hypertension (TPG > or = 15 mm Hg or PVR > or = 5 Wood units), whereas the 3- to 7-day and 8- to 30-day mortality rates were similar. Early post-transplant mortality (0 to 2 days and 8 to 30 days) was also significantly higher (15.9% vs 3.9% and 9.9% vs 2.8%, respectively; p < 0.05) in women compared with men. Women with severe preoperative pulmonary hypertension had higher (p < 0.05) 0- to 2-day post transplant mortality than comparable men. According to univariate analysis, recipients with preoperative TPG > or = 15 mm Hg had a significantly higher 30 day postoperative mortality rate, irrespective of their level of PVR. Furthermore, patients with severe preoperative pulmonary hypertension who underwent transplantation between 1980 and 1987 had a higher 0- to 2-day post transplant mortality rate compared with patients operated on after that time. Multiple logistic regression analysis identified female recipient sex and preoperative TPG but not preoperative PVR, era of transplantation, or recipient age as significant (p < 0.001 and p < 0.01, respectively) independent predictors of early post-transplant mortality. PMID- 8213448 TI - Familial calcification of aorta and calcific aortic valve disease associated with immunologic abnormalities. AB - We report three patients of the same family with linear calcification of the ascending aorta, severe calcific mixed aortic valve disease associated with increased levels of globulins, lambda-chain gammopathy, an increased T4/T8 lymphocyte ratio, and other immunologic abnormalities. None of the patients had syphilis, atherosclerosis, abnormalities of calcium or phosphorus metabolism, lymphadenopathy, or other systemic diseases. It is postulated that these cases and some previously reported in the literature as idiopathic represent a distinct pathologic entity, familial or sporadic, in which localized vascular and valvular calcific disease is associated with an underlying immunologic disorder or autoimmune process. PMID- 8213450 TI - Transdermal clonidine as an adjunct to nifedipine-GITS therapy in patients with mild-to-moderate hypertension. AB - Calcium channel blockers and central alpha-agonists are among the classes of antihypertensive drugs that yield the most favorable overall effects on risk factors for hypertension-related end-organ damage. An open-label prospective trial in 42 patients with a mean baseline blood pressure of 144/102 mm Hg sought to assess the usefulness of adjunctive treatment with transdermal clonidine (0.1 to 0.3 mg/day) in patients responding inadequately to nifedipine- gastrointestinal therapeutic system (GITS) (30 to 60 mg/day) monotherapy. Thirty nine patients who failed to reach the goal of a seated mean diastolic blood pressure of < 90 mm Hg when treated only with once-a-day nifedipine-GITS entered a transdermal clonidine (once a week) titration phase followed by an 8-week maintenance course of the two drugs combined. The 35 patients completing this last phase responded with a mean seated diastolic blood pressure of 127/87 mm Hg. Only six patients required the highest dose of clonidine for control. A 97% compliance rate with the transdermal medication contrasted with a compliance rate of only 73% for the oral nifedipine. Two of three patients who had contact dermatitis after wearing a transdermal clonidine patch withdrew from the trial prematurely; other minor side effects required no interruption of therapy. The nifedipine-clonidine combination not only achieved blood pressure control in these patients but may prove advantageous in combining the protective effects of the two agents against complications of the hypertensive syndrome. PMID- 8213449 TI - Detection of left-to-right shunt in atrial septal defect by negative contrast echocardiography: a comparison of transthoracic and transesophageal approach. AB - The occurrence of a right atrial negative contrast effect as an indicator of left to-right shunt was studied in 101 patients with atrial septal defect by peripheral venous contrast injection during transthoracic and transesophageal echocardiography. Confirmation of the diagnosis was provided by cardiac catheterization or by autopsy in 72 (72%) patients. The defect could be visualized directly in 57 (57%) patients during the transthoracic and in 93 (93%) during the transesophageal examination (p < 0.001). A negative right atrial echo contrast effect was observed in 53 of 92 (58%) patients from the transthoracic and in 86 of 92 (93%) patients from the transesophageal approach (p < 0.001). Among these were seven (7%) patients with an aneurysmal interatrial septum but no directly visible defect during conventional transesophageal imaging. Appearance of contrast in the left atrium indicating right-to-left shunting was seen in 70 of 92 (76%) patients from the transthoracic and in 91 of 92 (99%) patients from the transesophageal approach (p < 0.001). Contrast injection during transesophageal imaging also helped identify additional malformations in 12 (12%) patients. Thus transesophageal echocardiography with echo contrast injection is a very reliable diagnostic method in patients with suspected atrial septal defect. PMID- 8213451 TI - Metabolic characteristics of hypertension: importance of positive family history. AB - This study was performed to compare metabolic and endocrine characteristics of untreated hypertensive patients and normal controls. Measurements were made in age-matched, body mass index (BMI) matched, normotensive patients with (n = 40; age = 53; BMI = 28) and without (n = 39; age = 54; BMI = 27) a family history of hypertension and hypertensive patients with (n = 38; age = 53; BMI = 28) and without (n = 25; age = 54; BMI = 29) a family history of hypertension. Norepinephrine, renin activity, and total cholesterol blood concentrations were similar in normotensive patients with a positive family history of hypertension and in hypertensive patients with or without a family history. Similarly, there were no differences in plasma insulin concentrations or insulin/glucose ratios between the normotensive patients with a family history of hypertension and hypertensive patients with or without a family history. But in all three groups the values were significantly greater (at least p < 0.05 for each) than in the normotensive patients without a family history. Increases in systolic blood pressure during treadmill testing were 51 +/- 4 mm Hg in the normotensive patients with a family history, 50 +/- 3 mm Hg in hypertensives with a family history, and 45 +/- 5 mm Hg in hypertensives without a family history; these changes were all less (p < 0.05 for each) than in normotensives without a family history (65 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213452 TI - Echocardiographic diagnosis of aneurysm of the sinus of Valsalva. AB - Echocardiographic and Doppler data of 62 patients with ASOV are presented. Catheterization and angiography were performed in 38 cases and surgery in 25 of the 38. The origin of these aneurysms was the RCS in 56 cases, NCS in 5, and LCS in 1 case. Seven had unruptured aneurysms, 6 rising from RCS dissected into the ventricular septum, producing heart block in 4, AR in 5, mitral regurgitation in 1; 1 aneurysm rising from the LCS was asymptomatic. In other cases (n = 55) the aneurysm had ruptured into one of the cardiac chambers. Thirty-two of the 50 RCS aneurysms ruptured into the RVOT, 13 into the RV cavity, 2 into the RA, and 3 into the LV. Of the 5 NCS aneurysms, (3 ruptured into the RA, 1 into the RV, and 1 into both the RA and RV. Associated VSD was identified in 16 (25.8%) of 62 cases. All of these patients had RCS aneurysms that ruptured into the RVOT. Echocardiography missed VSD in three cases that at surgery were found to have VSD. AR was found in 34 of 62 cases. Echocardiography picked up discrete subaortic stenosis in two cases but missed subvalvar PS in 2 of the 3 cases. A detailed echocardiographic study (two-dimensional, Doppler, and color flow imaging) is accurate in the diagnosis of ASOV, in the identification of its site of origin and rupture, and in the evaluation of the associated defects; in the vast majority of cases, it can totally supplant the need for angiography. PMID- 8213453 TI - The role of the coronary collateral circulation in limiting myocardial ischemia and infarct size. AB - The role of coronary collateral circulation in limiting ischemia and infarction has been studied prospectively. Transient occlusion of a coronary artery angioplasty has provided evidence that collateral circulation decreases wall motion abnormalities, ST segment changes, and lactate production. Patients who have collateral flow also have a better outcome after coronary artery dissection and acute closure than patients without collateral flow. Collateral circulation also limits infarct size during acute myocardial infarction with and without thrombolysis. Although collateral flow may decrease coronary artery bypass graft patency in certain subgroups of patients, the perioperative infarct rate and mortality is decreased. Growth factors have been identified that increase the development collateral circulation and may improve ventricular function in the setting of myocardial infarction. PMID- 8213454 TI - Subacute ventricular free wall rupture complicating myocardial infarction. AB - Myocardial free wall rupture accounts for between 8% and 17% of mortality after myocardial infarction. In up to 40% of cases death occurs subacutely over a matter of hours, not minutes. Illustrative clinical cases and data suggest that a high degree of clinical suspicion, along with the early use of echocardiography, could significantly reduce mortality resulting from myocardial free wall rupture complicating myocardial infarction. Myocardial free wall rupture should be suspected in patients with recent myocardial infarction who have recurrent or persistent chest pain, hemodynamic instability, syncope, pericardial tamponade, or transient electromechanical dissociation. In this clinical situation, emergent echocardiography showing a pericardial effusion or pericardial thrombus is highly suggestive of free wall rupture. Surgical exploration and rupture repair is the definitive diagnostic and therapeutic procedure. PMID- 8213455 TI - Pulsed Doppler transesophageal echocardiographic determination of cardiac output in human beings: comparison with thermodilution technique. AB - Measurement of cardiac output is a clinically valuable and widely used index of cardiac function. Although transesophageal echocardiography has been used to assess left ventricular function, little data exist on the accuracy of this technique in the measurement of cardiac output. Therefore cardiac output derived by pulsed Doppler transesophageal echocardiography and thermodilution methods were compared in adult patients being mechanically ventilated. The left ventricular outflow tract diameter was determined from a transgastric long-axis view of the left ventricle by using the transverse plane and longitudinal plane of the transesophageal scope. The cross-sectional area of the left ventricular outflow tract was calculated from the diameter assuming a circular shape. Pulsed Doppler recordings were obtained at the left ventricular outflow tract. Doppler time-velocity integrals were measured from the leading edge of the velocity curve. Cardiac output derived by transesophageal echocardiography was calculated as time-velocity integral multiplied by left ventricular outflow tract area and heart rate. Cardiac output derived by transesophageal echocardiography from the transverse plane (n = 26) and longitudinal plane (n = 22) were correlated with simultaneous thermodilution measurements. Thermodilution-derived cardiac output demonstrated excellent correlation with cardiac output measured by using transesophageal echocardiography from the transverse plane (r = 0.97, SEE = 0.84 L/min; p < 0.0001) and longitudinal plane (r = 0.95, SEE = 0.97 L/min; p < 0.0001). Transesophageal echocardiography is a promising technique in the measurement of cardiac output and expands the clinical use of this modality in the assessment of cardiac function. PMID- 8213456 TI - Innovative emergency defibrillation methods for refractory ventricular fibrillation in a variety of hospital settings. AB - This article reviews the ability of innovative rescue defibrillation techniques for the treatment of refractory ventricular fibrillation. These data were obtained in a variety of hospital settings at the University of California, San Francisco, from 1986 to 1992. Innovative rescue defibrillation techniques were applied to 15 patients with refractory ventricular fibrillation having failed > or = 2 high-energy transthoracic shocks in a variety of hospital settings. Intracardiac defibrillation was performed from a right ventricular catheter to a posterior patch in nine patients who had refractory ventricular fibrillation in the course of invasive electrophysiologic testing. Emergency simultaneous transthoracic and epicardial defibrillation was successfully performed with standard paddles placed over the thorax in contact with epicardial patch or pacing lead connectors in two patients in the operating room who underwent implantable cardioverter-defibrillator insertion and failed standard rescue defibrillations. Transesophageal defibrillation was performed in four patients in the emergency department who had a refractory ventricular fibrillation in the field. Intracardiac defibrillation successfully terminated refractory ventricular fibrillation in 9 of 9 patients in the electrophysiology laboratory. Similarly, emergency simultaneous transthoracic and epicardial defibrillation restored sinus rhythm in two patients in the operating room. Transesophageal defibrillation performed after 50 minutes of cardiac arrest successfully terminated ventricular fibrillation in each patient. Thus alternative methods now exist that permit rescue defibrillation in a variety of hospital emergency settings. These techniques are performed with simple-to-use equipment that is compatible with standard defibrillators. PMID- 8213457 TI - In vivo radiofrequency thermal balloon angioplasty of porcine coronary arteries: histologic effects and safety. AB - The purpose of this study was to assess the safety and histologic effects of radiofrequency thermal balloon angioplasty in the coronary vasculature of normal pigs. Radiofrequency thermal balloon angioplasty was performed in 30 coronary arteries of 16 nonatherosclerotic pigs. Heated inflations were performed at either 50 degrees, 60 degrees, or 70 degrees C for 30 or 60 seconds, and were compared with five nonheated inflations in five additional arteries. All balloon inflations were performed at 2 atm pressure with a balloon/vessel diameter ratio of 1.2 to 1. Heart rate, arterial pressure, and left ventricular pressure were monitored continuously for each animal. A 12-lead ECG, coronary angiography, and two-dimensional transthoracic echocardiography were performed before and 1 hour after each balloon inflation. Each animal was subsequently put to death for postmortem cardiac examination. Heated inflations were well tolerated in 28 of the 30 arteries without significant adverse effects. During one inflation, ventricular fibrillation occurred because of prolonged ischemia from an occlusive guiding catheter. In another artery, a heated inflation resulted in a dissection with a transient decrease in distal coronary flow. Histologic examination revealed a significant increase in wall thinning and elastic fiber straightening with heating at 70 degrees C for both 30 and 60 seconds, and a significant increase in intracoronary thrombus with heating at 70 degrees C for 60 seconds. Depth of periarterial myocardial heat necrosis paralleled the increase in temperature, with an average depth of 166 microns at 50 degrees C, 312 microns at 60 degrees C, and 1031 microns at 70 degrees C. In vivo, radiofrequency coronary angioplasty can be performed relatively safely without significant electrical, hemodynamic, or ischemic changes beyond those seen with conventional nonthermal angioplasty. The extent of heat-induced vessel wall thinning, elastic tissue straightening, intracoronary thrombus formation, and periarterial myocardial necrosis are all related to balloon temperature or duration of heating. PMID- 8213458 TI - Balloon expandable intravascular stents: aortic implantation and late further dilation in growing minipigs. AB - Intravascular stents have been implanted in children with congenital and acquired vascular stenoses. Little information is known regarding the long-term results in growing patients, the implantation of multiple stents (in series), and the feasibility of further dilation. Nine stents were implanted in the abdominal aortas of 6 mini-pigs; in 3 pigs, 2 stents were implanted in series. Five pigs were recatheterized 196 +/- 17 days after stent implant. All stents were patent, with mild narrowing at the stent relative to the adjacent aorta; further stent dilation was performed. The stent diameter increased from 8.3 +/- 0.6 mm to 11.2 +/- 1.3 mm (p = 0.002), and the narrowing was relieved. These five pigs were catheterized 253 +/- 73 days after stent redilation. Each stent was patent without narrowing or pressure gradient. We conclude that intravascular stents do not interfere with normal growth, can be implanted in series, and can be further dilated. PMID- 8213459 TI - Angioplasty of the right coronary artery with origin of all three coronary arteries from a single ostium in the right sinus of Valsalva. PMID- 8213460 TI - Do arterial endothelin 1 levels affect local arterial stiffness? PMID- 8213461 TI - Hemodynamic and myocyte mitochondrial ultrastructural abnormalities in arrhythmogenic right ventricular dysplasia. PMID- 8213463 TI - Dermatomyositis with pericardial tamponade and polymyositis with pericardial effusion. PMID- 8213462 TI - Specific myocardial disease caused by multisystemic triglyceride storage in Jordans' anomaly. PMID- 8213464 TI - Very early appearance of Kaposi's sarcoma after cardiac transplantation in Sephardic Jews. PMID- 8213465 TI - Alabama pharmacies offer AIDS education. PMID- 8213466 TI - Reimbursement for outpatient biotech drugs--Part 2. PMID- 8213467 TI - Mix-ups with Norvasc and Navane. PMID- 8213468 TI - Improving adherence in patients with asthma. PMID- 8213469 TI - Children can help control their own asthma. PMID- 8213470 TI - Why I no longer recommend Triaminic Syrup. PMID- 8213471 TI - Triaminic reformulation: why we did it. PMID- 8213472 TI - Clinical review of canthaxanthin ('tanning pills'). PMID- 8213473 TI - Use of calcium channel antagonists for cardiovascular disease. AB - Until recently, only three calcium channel antagonists--verapamil, diltiazem and nifedipine--were available for managing cardiovascular disorders such as hypertension and ischemic heart disease. In the past few years, however, several dihydropyridine calcium channel antagonists, including nicardipine, isradipine, felodipine, nimodipine, and amlodipine, have been marketed. Others are currently awaiting FDA approval. In addition, bepridil, which belongs to a new class of calcium channel antagonists, has recently been marketed for refractory angina pectoris. Clinical uses of calcium channel antagonists have been expanded since the 1970s to include management of cardiovascular disorders such as supraventricular arrhythmias, CHF secondary to diastolic dysfunction, and myocardial reinfarction in selected patients. Calcium channel antagonists are also being investigated for prevention of atherosclerosis. Calcium channel antagonists are a heterogeneous group of pharmacologic agents. Differences in tissue selectivity are largely responsible for the variations in hemodynamic and electrophysiologic properties of these agents. Thus, their clinical uses and side effect profiles differ. These differences must be taken into consideration in the selection of the most appropriate agent for a specific indication. Potential advantages of some of the newer dihydropyridine calcium channel antagonists include less frequent dosing (amlodipine and isradipine) and little or no negative inotropic effect (nicardipine, felodipine, amlodipine, isradipine) compared with the prototype calcium channel antagonists. Additional clinical experience with these newer agents is required, however, before their role in the management of cardiovascular disorders can be fully delineated. The availability of sustained-release formulations of verapamil, diltiazem, nifedipine, felodipine, and nicardipine, as well as the recent marketing of calcium channel antagonists with relatively long half-lives (amlodipine and isradipine), makes once- or twice-daily dosing possible with most calcium channel blockers. However, selection of a particular agent will depend on several factors, including clinical efficacy, side effect profile, cost, and patient characteristics such as concomitant disease states and baseline hemodynamic status. PMID- 8213474 TI - Smoking and drug metabolism. PMID- 8213475 TI - Monoclonal antibody-based self-testing products. PMID- 8213476 TI - The health sciences need a controlled vocabulary. PMID- 8213477 TI - Selecting a fax modem. PMID- 8213478 TI - Alternative medicine: poised to move ahead. PMID- 8213479 TI - Counseling special populations on oral health care needs. PMID- 8213480 TI - Active listening: a key to effective communication. PMID- 8213481 TI - Ethical decision making in pharmacy. PMID- 8213482 TI - So your child has chickenpox.... PMID- 8213483 TI - Contraception: what pharmacists should tell their patients. PMID- 8213484 TI - Colorectal cancer testing. PMID- 8213485 TI - Preliminary evaluation of an active end-of-service-life indicator for organic vapor cartridge respirators. AB - Data are presented on a microwatt chemiresistor microsensor for use with negative pressure organic vapor respirators. This sensor would operate at or within a sorbent bed and detect parts per million levels of chemical vapors and/or gases as a function of sensor resistance. Sensors were evaluated against four challenge concentrations of ethyl acetate (750 ppm, 1000 ppm, 1500 ppm, and 2000 ppm). Direct comparison of breakthrough times and curves for the chemiresistor microsensor and a standard infrared (IR) detector system were made. The chemiresistor sensor responses were found to correlate well with the IR system. The evaluation showed that although the chemiresistor sensors were not as sensitive as the IR detectors, they could be used if located inside the charcoal bed. Thus, these sensors could function as organic-vapor detectors and could be used in cartridge applications. However, further improvements in stability and sensitivity of these chemiresistor sensors is necessary. PMID- 8213486 TI - Determining the service lives of organic-vapor respirator cartridges for nitroglycerin under workplace conditions. AB - Results of a field study that estimated the service lives of several different brands of organic-vapor respirator cartridges for nitroglycerin are presented. Respirator carbon tubes (RCTs) were used to sample in a workplace where gun powder was manufactured and where nitroglycerin levels varied from approximately 0.1-0.7 mg/m3. Tenax adsorbent tubes were used to monitor for nitroglycerin upstream and downstream of RCTs and were subsequently analyzed by a gas chromatography method. A series of 10 trials failed to find evidence of nitroglycerin breakthrough. Estimates of the minimum service lives of respirator cartridges varied from 7-81 hours for nitroglycerin levels of 1.0 mg/m3, 10 times the current Occupational Safety and Health Administration Permissible Exposure Level. One trial specifically examined the potential of nitroglycerin to prematurely break through a cartridge due to bed migration, and results failed to indicate this as a potential problem. A field validation of the Tenax adsorbent tube method for nitroglycerin monitoring resulted in an accuracy of +/- 77-88% at the 95% confidence level. An unexpected finding was that up to 10% of the ambient nitroglycerin collected was adsorbed to an aerosol. This finding led to the recommendation that the addition of a prefilter to an organic vapor cartridge may be required when using air-purifying respirators to protect workers from some nitroglycerin exposures. PMID- 8213487 TI - Occupational exposure to 4,4'-bipyridyl vapor and aerosol during paraquat manufacturing. AB - The mass concentrations of both vapor and aerosol phases of 4,4'-bipyridyl were determined by a glass fiber filter and an XAD-2 tube in a paraquat factory. The size distributions of 4,4'-bipyridyl aerosols and particles < 10 microns were measured by a six-stage cascade impactor. The mass concentrations of 4,4' bipyridyl aerosols were in the range of 81.9 to 159.9 mg/m3 with an average 4,4' bipyridyl vapor mass concentration of 3.1 mg/m3 at the top of the open tank. On the average, the mass ratio of vapor phase to aerosol phase of 4,4'-bipyridyl was 0.025. Therefore, the aerosol phase is the major form of 4,4'-bipyridyl exposure to the workers in this environment. From the 4,4'-bipyridyl concentrations measured by the sampling systems of an XAD-2 tube alone and a filter followed by an XAD-2 tube, the 4,4'-bipyridyl aerosol collection efficiency of the XAD-2 tube was found to be approximately 50%. The average mass concentrations of less than 10 microns aerosols and 4,4'-bipyridyl aerosol in the occupational environment were 0.42 mg/m3 and 1.26 micrograms/m3, respectively. The mass median aerodynamic diameter (geometric standard deviation) of particles < 10 microns and 4,4' bipyridyl aerosol are 3.50 microns (2.35) and 3.47 microns (2.58), respectively. The major mass fraction of 4,4'-bipyridyl aerosol occurred in the 3.3-5.8 microns size range. The enclosure efficiencies of a hood cover attached to a suction tube were found to be 88% and 82% for both aerosol and vapor phases of 4,4'-bipyridyl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213488 TI - Exposure to blood-containing aerosols in the operating room: a preliminary study. AB - A personal sampling study was conducted to assess exposure to blood aerosols in the operating room. The breathing zones of primary and assistant surgeons were monitored using a personal cascade impactor configured with three stages corresponding to effective cut-off aerodynamic diameters of 14.8 microns, 3.5 microns, and 0.52 microns, respectively. Hemastix was used to assess the hemoglobin content of each particle size fraction. The arithmetic mean exposure concentration for primary surgeons (n = 14) was 1.4 micrograms Hb/m3 (range, none detected to 7.4 micrograms Hb/m3), while that for assistant surgeons (n = 12) was 1.8 micrograms Hb/m3 (range, 0.3 to 4.8 micrograms Hb/m3). Hemoglobin was detected in Stage 2 in 26 (90%) of the samples, in Stage 5 in 19 (66%) of the samples, and in Stage 8 in 11 (38%) of the samples. These data show that the mucous membrane lining of the upper respiratory tract and alveolar macrophages in the gas-exchange region are likely to be exposed to aerosolized blood in the operating room. Until further research determines the potential of infected blood aerosols to transmit disease, the authors recommend the proper use of respiratory protection equipment instead of surgical masks because the latter do not offer adequate protection. PMID- 8213489 TI - Case study "carcinogens:" the MBOCA TLV example. PMID- 8213490 TI - Homozygous familial hypercholesterolemia: a paradigm for phenotypic variation. AB - Most, if not all, inborn errors of metabolism manifest phenotypic heterogeneity in their clinical presentation. The term "penetrance" has been used to describe the degree to which a given genotype expresses itself in the phenotype of the individual. Although many explanations for this phenomenon have been put forward, the molecular bases for this have been difficult to define. The investigation of the disease familial hypercholesterolemia (FH) has been used as a paradigm at many different levels. This condition, in which a wide variety of mutations in the low density lipoprotein (LDL) receptor gene leads to elevated concentrations of LDL particles has a wide array of clinical manifestations that are variably expressed in both patients who are heterozygous and homozygous for mutations at the LDL receptor allele. Progress in understanding lipoprotein metabolism, atherogenesis, and the development of molecular biology and transgenic expression techniques converge to utilize homozygous FH as a paradigm for understanding the molecular basis of penetrance. Elucidation of the key factors in altering the clinical features expressed by patients with FH have theoretical implications in understanding the polygenic nature of atherosclerosis as well as practical ramifications in the treatment of patients with FH. PMID- 8213491 TI - Diagnosis and case finding in familial hypercholesterolemia. AB - Heterozygous familial hypercholesterolemia (hFH) is known to be associated with a high risk for development of coronary disease. However, several issues still remain as to whether this condition merits a special approach to diagnosis and case finding. It appears that hFH meets the World Health Organization criteria as a condition worthy of a screening program. However, none of several current strategies appears to be successful in the identification of even a majority of hFH cases. These strategies include community-wide programs to test everyone for total serum cholesterol levels, the testing of first degree family members of hFH patients or family members of patients with coronary disease at age < or = 55 years, or even the screening of patients with premature vascular events. The barriers for patients and physicians to carry out screening recommendations need to be identified and removed, including the need to sensitize primary care providers about the importance of identifying those with hFH. PMID- 8213492 TI - Documented need for more effective diagnosis and treatment of familial hypercholesterolemia according to data from 502 heterozygotes in Utah. AB - A project to help Utah residents with heterozygous familial hypercholesterolemia (FH) identified affected individuals by collecting detailed questionnaires from: (1) very high-risk persons in computer files of screening data (very high cholesterol levels, very early coronary artery disease, and strong positive family history); (2) confirmed FH index cases from a university lipid clinic; and (3) relatives of any confirmed FH cases. Questionnaires were received from 2,143 persons identifying 101 living index cases and 502 relatives meeting the criteria for the diagnosis of FH. Finding new FH heterozygotes was about one fourth as expensive by tracing relatives of confirmed FH cases by evaluating very high-risk persons. Of those meeting criteria for the diagnosis of heterozygous FH, only 31% reported being told by their physicians that they had FH, only 42% indicated that they were taking a cholesterol-lowering prescription medication, and only 23% had reasonably controlled cholesterol levels (below the 90th percentile). However, the data also suggest that good control is achievable in motivated patients. Among 106 FH heterozygotes who were early responders to a second follow-up questionnaire, 79% were taking prescription medications, of whom 49% had achieved cholesterol levels below the 90th percentile, and 17% even achieved cholesterol levels below the 50th percentile. We conclude that most patients with heterozygous FH are not diagnosed and not adequately treated. We demonstrated how many of these persons needing help could be identified efficiently by tracing relatives of known index cases. PMID- 8213493 TI - Development of a program for identification of patients with familial hypercholesterolemia in British Columbia: a model for prevention of coronary disease. AB - We have developed a targeted approach to identification of high-risk patients in British Columbia, Canada, as an initial strategy for the prevention of coronary disease. Patients with the diagnosis of familial hypercholesterolemia have been identified through the Lipid Clinic. First degree relatives of these persons and subsequently identified individuals will be screened for the presence of hypercholesterolemia. Using this approach, the likelihood of identifying persons at high risk is high, close to 50%. The program will also allow collection of data on factors affecting the expression of hyperlipidemia and atherosclerosis and their response to therapy. In an effort to establish the infrastructure that would be necessary for identification and management of such patients throughout the province, a Lipid Clinic Outreach Program has been developed. The objective is to provide each community in the province with expertise to manage hyperlipidemia without traveling to a major urban area. With this infrastructure in place, this will serve patients who have premature atherosclerosis due to other causes and will also form the framework for dissemination of heart health policies and programs by different levels of government, voluntary and professional organizations, as well as the private sector. From a targeted family centered pilot program, a broad approach to the prevention of coronary artery disease in this community will be possible. PMID- 8213494 TI - Identification and treatment of heterozygous familial hypercholesterolemia in children and adolescents. AB - Heterozygous familial hypercholesterolemia (FH) is completely expressed at birth and early in childhood by significant elevations in plasma total and low density lipoprotein (LDL) cholesterol levels. High density lipoprotein cholesterol can be low in such FH children; the triglyceride levels are usually within the normal range. Screening of children for heterozygous FH using a LDL cholesterol level is reasonably efficient in families with known FH, but for general population screening, the LDL cholesterol level is often too nonspecific. Screening of offspring with a positive family history of premature coronary artery disease will provide a panoply of different lipoprotein phenotypes, reflecting the presence of other genetic conditions, including familial combined hyperlipidemia. Guidelines have been developed by the National Cholesterol Education Program (NCEP) Expert Panel on Blood Cholesterol levels in Children and Adolescents to assist in the evaluation and treatment of children with high LDL cholesterol levels. Although heterozygous FH probably counts for < or = 5% of premature coronary artery disease, its identification and treatment are important, because FH often causes marked premature coronary artery disease early in adulthood, and can be successfully treated with a combined dietary and drug approach. PMID- 8213495 TI - Who should treat familial hypercholesterolemia? AB - The treatment of various manifestations of familial hypercholesterolemia can involve a variety of health professionals over the lifetime of a given patient. The first task is to diagnose the condition. This should be done by primary physicians, i.e., pediatricians, family practitioners and internists. The same professionals, with help from dietitians as necessary, should treat the hypercholesterolemia in most cases. Homozygotes and difficult to treat heterozygotes should be referred to endocrinologists or lipidologists. The various cardiovascular manifestations, at one time or another, may require consultation with cardiologists, neurologists, radiologists, and cardiac or vascular surgeons. Physiatrists and physical and occupational therapists also may contribute to patient care. PMID- 8213496 TI - Importance of diet in the treatment of familial hypercholesterolemia. AB - The principal goal of dietary treatment of heterozygous familial hypercholesterolemia (hFH) is the reduction of the plasma low density lipoprotein (LDL) cholesterol. This is best accomplished by enhancing the activity of LDL receptors and, at the same time, depressing liver synthesis of cholesterol. Both cholesterol and saturated fat down-regulate the LDL receptor and inhibit the removal of LDL from the plasma by the liver. Saturated fat down-regulates the LDL receptor, especially when cholesterol is concurrently present in the diet. The total amount of dietary fat is also important. The greater the flux of chylomicron remnants into the liver, the greater is the influx of cholesterol ester. In addition, factors that affect LDL synthesis could be important. These include excessive calories (obesity) that enhance very low density lipoprotein (VLDL) and, hence, LDL synthesis, and weight loss and omega-3 fatty acids, which depress synthesis of VLDL and LDL. The optimal diet for treatment of children and adults has the following characteristics: cholesterol (100 mg/day), total fat (20% of kcal, 6% saturated with the balance from omega-3 and omega-6 polyunsaturated and monounsaturated fat), carbohydrate (65% kcal, 67% from starch), and protein (15% kcal). This low-fat, high-carbohydrate diet can lower the plasma cholesterol 18-21%. A new concept, the Cholesterol-Saturated Fat Index, allows people to evaluate any foodstuff for its potential to elevate the plasma LDL cholesterol level. It is an antithrombotic diet, thrombosis being another major consideration in preventing coronary heart disease. Also, it contains significant amounts of antioxidants and fiber. Dietary therapy is the mainstay of treatment of hFH to which various drug therapies can be added. PMID- 8213497 TI - How effective is drug therapy in heterozygous familial hypercholesterolemia? AB - The goals of drug therapy in adult patients with heterozygous familial hypercholesterolemia (FH) are directed at reducing plasma concentrations of low density lipoproteins (LDL), with a secondary goal in selected patients to concurrently decrease elevated plasma concentrations of lipoprotein(a), triglycerides, and potentially exert favorable effects on the concentrations of high density lipoproteins (HDL). Desirable goals of therapy are to reduce concentrations of LDL cholesterol to < 130-160 mg/dL in patients without evidence of coronary artery disease, and, in my opinion, to < 100 mg/dL in patients with evidence of coronary artery disease. The bile acid sequestrants, cholestyramine and colestipol, reduce LDL concentrations by 23-36%, when given in doses of 4-6 scoops/day, but reduce LDL concentrations to desirable levels in only 10-15% of patients. Similarly, nicotinic acid, in doses of 3-6 g/day, is capable of reducing LDL concentrations by up to 30%, but the majority of patients still remain hypercholesterolemic. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, which include lovastatin, simvastatin, and pravastatin, are the most effective of the currently available drugs and show dose-dependent effects on the concentrations of LDL cholesterol, which decrease by 20-45% in response to these drugs when used over the full dosage range. However, even with these agents, concentrations of LDL cholesterol remain > 200 mg/dL in one-third of male and female patients with heterozygous FH and remain > 160 mg/dL in 75-80% of treated patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213498 TI - Therapeutic strategies for familial hypercholesterolemia based on somatic gene transfer. AB - Inherited dyslipidemias are important risk factors for the premature development of coronary artery disease. One example is an inherited deficiency of low density lipoprotein (LDL) receptors that leads to the syndrome familial hypercholesterolemia (FH). We have used FH as a model for developing new approaches for treating this group of disorders by somatic gene therapy. Experiments in animal models that led to the initiation of a clinical trial of homozygous FH will be presented in this review. PMID- 8213499 TI - Familial hypercholesterolemia in French-Canadians: taking advantage of the presence of a "founder effect". AB - The frequency of familial hypercholesterolemia (FH) in the Province of Quebec is twice that observed in most population samples. In the French-Canadian population, 5 mutations in the low density lipoprotein (LDL) receptor gene account for 76% of FH cases diagnosed using clinical and biochemical criteria. One of these mutations, a > 10 kilobase (kb) deletion at the 5' end of the gene involving the promoter and exon 1, is present in 60% of FH patients studied in Montreal. This high frequency is attributable to a "founder effect." Contribution to this founder effect included strategies in 17th century France for the settlement of a small number of pioneers, local incentives for early marriages and large families, and geographic and cultural isolation; these factors also favored endogamy. The > 10 kb deletion is present on only one haplotype in all patients studied so far (homozygotes and heterozygotes), a major advantage for studies relating phenotypic variation to haplotype variation in the normal LDL receptor allele of these hemizygous patients. Indeed, the presence of founder effects facilitates screening, genetic counseling, and treatment. It also confers a number of advantages for research: (1) the search for new causes of FH in the 24% unaccounted for to date; (2) the study of the geographic distribution of mutations and population movements; (3) the identification of gene-gene interactions in the etiology of disease; (4) the evaluation of factors modulating phenotypic expression and search for LDL-lowering genes; and (5) the study of genetic determinants of therapeutic response. PMID- 8213500 TI - Psychological and ethical considerations in screening for disease. AB - Coronary artery disease is the leading cause of death in the United States. Serum cholesterol is a widely used screening test to detect persons at high risk for coronary artery disease, including those with familial hypercholesterolemia. However, universal screening of currently healthy persons is not without risk. Previous experience in screening for sickle cell anemia and hypertension has shown that these risks include misunderstanding of test results, misdiagnosis, labeling, stigmatization, and decreased psychological well-being. Results of screening programs may be misused by industry or insurance companies to exclude individuals from positions or benefits. Consideration of these harms suggests that screening should not be implemented until certain safeguards are in place. Physicians and the public should be educated about the potential risks and benefits of screening. Screening tests should be accurate, reliable, valid, and of demonstrated sensitivity. Informed consent for screening should be obtained. Follow-up surveillance and recommended treatments, including dietary counseling and drug therapy, should be available to all individuals identified as being at high risk regardless of their socioeconomic status. Finally, procedures to protect the right to privacy of individuals and their families should be implemented well in advance of the actual screening. PMID- 8213501 TI - Measuring adherence with therapy for chronic diseases: implications for the treatment of heterozygous familial hypercholesterolemia. AB - The failure of patients to adhere adequately to prescribed medication and behavioral regimens is an important medical problem. Poor adherence is most common when the treatment regimen is preventive rather than curative, when patients are asymptomatic, and when the duration of treatment is long. For these reasons, adherence with dietary therapy for hypercholesterolemia is well recognized to be a significant clinical and research challenge. Medication adherence has been acknowledged to be a problem for those treatments with significant side effects, such as flushing and pruritus or the low palatability of bile acid sequestering agents. The availability of drugs that lack these effects has long been viewed as an important contribution to improving overall patient compliance. However, the literature on patient adherence with life-long treatment regimens that are simple and palatable (e.g., antihypertensives) suggests that while these improved treatments can enhance adherence, the overall rates of patient compliance still average only 50%. The fact that patients with heterozygous familial hypercholesterolemia are at high risk for early coronary artery disease and death if they fail to adhere to therapy is not sufficient to assure high rates of appropriate therapy over long periods of time, as demonstrated by the poor or erratic adherence commonly reported to treatments for other life-threatening diseases, such as advanced renal disease, hemophilia, and type I diabetes. The measurement of patient adherence to hypercholesterolemia therapy is often neglected in clinical practice and inadequate in hypercholesterolemia research.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213502 TI - Cost-effectiveness considerations in the treatment of heterozygous familial hypercholesterolemia with medications. AB - When used for the primary prevention of coronary heart disease in persons with heterozygous familial hypercholesterolemia (hFH), a hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor is projected to be effective and to have very favorable cost-effectiveness ratios at low-to-medium doses. For example, 20 mg of lovastatin per day is estimated to save lives and save money in all men ages 35-44 years with hFH and in women ages 35-44 years with hFH and any other risk factor. The estimated incremental cost effectiveness of 40 mg compared with 20 mg of lovastatin for individuals with hFH ages 35-44 years was less than $45,000 per year of life saved in men with > or = 1 other risk factors and women with > or = 2 other risk factors. The estimated incremental cost-effectiveness ratio of 80 mg compared with 40 mg/day was substantially higher ($100,000 or more per year of life saved) even in the highest risk persons. The estimated cost effectiveness ratios for primary prevention in hFH were reasonably similar to the favorable ratios for secondary prevention in the general population but substantially better than the estimated ratios for primary prevention in other adults with high cholesterol levels. Any national recommendations regarding the use of medications for individuals with hFH must include cost considerations. Our analyses support the use of low-to-moderate doses of high-cost medications for primary prevention in these patients. PMID- 8213503 TI - Ethics, genetic prediction, and heart disease. AB - As we identify genes predictive of diseases such as heart disease, stroke, or cancer, we may unwittingly deprive individuals and families at risk of such diseases from access to health care. This is a problem in distributive justice. Commercial health insurance is built along lines similar to other forms of commercial insurance in which the notion of "actuarial fairness" plays a key role. Actuarial fairness contends that parties seeking insurance ought to pay according to their respective risks of filing a claim. Underwriting is the process by which insurers estimate the likelihood that an applicant would be making a claim. The human genome project has brought the latent ethical problems in commercial health insurance to the surface. In the scenario feared by insurers, predictive genetic tests will filter into general medical practice. Individuals who learn that they are at increased risk of such disease are more likely to purchase insurance. Such behavior is known as "adverse selection" by the insurance industry. Individual companies, in an effort to avoid adverse selection, may seek genetic information about their prospective customers, and other companies may follow suit. Such a scenario has led to the establishment of a national Task Force on Genetic Information and Insurance under the aegis of the human genome project. The Task Force seeks to clarify the empirical and moral components of the controversy. Key questions include the social purpose of health insurance, whether adverse selection is a genuine concern in the context of genetic testing, and the appropriateness of risk underwriting for access to health care.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213504 TI - Study of myocardial infarct remodeling by single-photon emission computed tomographic imaging. AB - Left ventricular (LV) remodeling after Q-wave anterior acute myocardial infarction (AMI) was examined with single-photon emission computed tomographic thallium imaging. Initial (after adenosine infusion) and 4-hour delayed reinjection images were obtained in 34 patients aged 65 +/- 12 years. Short-axis slices from the delayed images were quantitatively analyzed by measuring the outer and inner diameters, and wall thickness. The results were compared with those in a group of normal subjects. The outer diameter was greater in patients than in normal subjects at the apical, mid- and basal levels (all p < 0.01); the average outer diameter was 16.9 +/- 1.9 mm in patients, and 12.2 +/- 1.3 mm in normal subjects (p < 0.001). Similarly, the inner diameter was greater in patients than in normal subjects at the 3 levels (all p < 0.05); the average inner diameter was 6.5 +/- 1.8 mm in patients, and 4.7 +/- 1.3 mm in normal subjects (p < 0.01). Wall thickness was greater in patients than in normal subjects (5.2 +/- 0.5 vs 3.8 +/- 0.5 mm; p < 0.0001). There were significant correlations between LV dilation and time elapsed (in weeks) since AMI (r = 0.57; p < 0.005), and the size of the perfusion abnormality (r = 0.44; p < 0.03). Thus, LV dilation occurs after Q-wave anterior AMI, and is related to infarct size and duration. These changes can be studied by single-photon emission computed tomographic thallium imaging. PMID- 8213505 TI - Characteristics of patients with nonfatal cardiac arrest 3 to 180 days after acute myocardial infarction. AB - Patients who survive a tachyarrhythmic cardiac arrest in the first 6 months after acute myocardial infarction (AMI) are at risk for recurrent arrests, but the magnitude, timing and characteristics of this phenomenon are unknown. This study characterizes the nature of recurrent tachyarrhythmic cardiac arrests in the absence of reversible factors or new myocardial necrosis in patients between 3 and 180 days after AMI. We retrospectively assessed 28 patients (mean age 61 +/- 12 years) who survived an initial cardiac arrest a median of 10 days after AMI. Mean left ventricular ejection fraction was 36 +/- 9%. Fourteen patients (50%) had at least 1 recurrence of cardiac arrest, and 10 had > 2 arrests. Almost all (92%) recurrent cardiac arrests occurred within 5 days of the preceding arrest, and the high-risk periods were similar after the first, second or third cardiac arrest. Very fast ventricular tachycardia (mean cycle length 212 +/- 30 ms) was the documented responsible arrhythmia in 44 of 51 cardiac arrests. The morphology was either polymorphic, monomorphic or sinusoidal. No clinical or laboratory values could be found that predicted whether a patient would have a recurrent arrest. Nineteen patients (68%) survived to leave the hospital and have been followed for up to 96 months. For these, actuarial 5-year overall survival was 76% and actuarial 5-year arrhythmia-free probability was 80%. Thus, patients who survive a cardiac arrest in the first 6 months after AMI are at high risk of recurrent cardiac arrest for a further 5 days, and the arrests are due to characteristically fast ventricular tachycardias.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213506 TI - How the exercise electrocardiogram is used in clinical practice in patients with suspected coronary artery disease. AB - Clinical use of a test should be evaluated not only on the change of pretest probability but also on the increased confidence in the judged probability, and on the decision of recommending additional tests or therapy after test results. Before and after the test, cardiologists referring a patient for exercise electrocardiogram for suspected coronary artery disease were asked to estimate the probability of coronary artery disease and the minimal and maximal value of their estimate (plausible range), to judge whether to refer the patient for coronary angiography, and to specify patient's treatment. After the test, the percentage of patients with estimated probability < or = 20% increased (from 53 to 69%; p = 0.005) and the percentage of patients with intermediate probability (between 21 and 80%) decreased (from 37 to 16%; p = 0.0001). The mean plausible range decreased from pre- to post-test assessment (31 +/- 23 to 15 +/- 16%; p = 0.0001), indicating an increase in cardiologists' confidence in their estimates. After the test, the percentage of cardiologists who wished to either refer or not refer patients for coronary angiography increased (from 4 to 13%, p < 0.005; and from 37 to 65%, p < 0.0001, respectively). Test results enable cardiologists to change the assessment of disease probability, the confidence in their own estimates, and their judgment of whether to refer patients for coronary angiography. PMID- 8213507 TI - Effects of sublingual nitroglycerin on the gas exchange response to exercise in stable angina pectoris. AB - To quantitate changes in gas exchange variables that occur after administration of sublingual nitroglycerin in patients with stable angina pectoris, a randomized double-blind 2-period crossover study was performed with continuous expired gas exchange analysis and progressive exercise using individualized ramp treadmill protocols. Significant reductions in minute ventilation and respiratory rate were observed at 5 minutes of exercise during nitroglycerin therapy. Gas exchange variables i.e., minute ventilation, carbon dioxide production and oxygen uptake were significantly increased at the onset of angina after nitroglycerin administration. When techniques for optimizing the assessment of cardiopulmonary function were used, significant improvements in gas exchange variables were demonstrated in stable angina pectoris after administration of sublingual nitroglycerin. PMID- 8213508 TI - Multicenter trial of ionic versus nonionic contrast media for cardiac angiography. The Iohexol Cooperative Study. AB - Contrast agents used for cardiac angiography are different in regard to ionicity, osmolality and physiologic effects. The nonionic contrast media have been shown to have less toxic effects and a better safety profile than do higher osmolar agents. To better assess this risk, clinically stable patients undergoing cardiac angiography were stratified according to the presence of diabetes mellitus, and level of serum creatinine, and then randomized to receive either iohexol (Omnipaque 350) or sodium meglumine diatrizoate (Renografin 76). All adverse events that occurred during and immediately after angiography were tabulated. A multivariate model was used to identify patients at increased risk for adverse outcome. The 1,390 patients were randomized to iohexol (n = 696) or diatrizoate (n = 694). Significant differences were found in the number of patients with contrast media-related adverse (iohexol vs diatrizoate: 10.2 vs 31.6%; p < 0.001) and cardiac adverse (7.2 vs 24.5%; p < 0.001) events. Severe reactions and the need for treatment were more frequent with diatrizoate than with iohexol, but there was no difference in the incidence of death. The presence of New York Heart Association classification 3 or 4 and serum creatinine > or = 1.5 mg/dl predicted a higher incidence of adverse events as a result of contrast media alone. Use of iohexol is associated with a lower incidence of all types of adverse events during cardiac angiography than is diatrizoate. PMID- 8213509 TI - Cholesterol lowering, low cholesterol, and mortality. AB - Cholesterol lowering in both primary and secondary prevention has been clearly demonstrated to lower coronary morbidity and, in secondary prevention, to lower coronary mortality as well. Putative dangers of cholesterol lowering remain unproven. Population studies linking low cholesterol to noncoronary mortalities do not demonstrate cause-and-effect relations. In fact, based on current studies, the opposite is more likely to be the case. Neither gender nor age should automatically exclude persons from cholesterol screening. Drug intervention, however, should be used conservatively, particularly in young adults and the elderly. Drugs should be used only after diet and lifestyle interventions have failed. The evidence linking high blood cholesterol to coronary atherosclerosis and cholesterol lowering to its prevention is broad-based and definitive. Concerns about cholesterol lowering and spontaneously low cholesterols should be pursued but should not interfere with the implementation of current public policies to reduce the still heavy burden of atherosclerosis in Western society. PMID- 8213510 TI - Effectiveness of radiofrequency catheter ablation for treatment of atrial tachycardia. AB - Catheter ablation has been used to treat atrioventricular node reentrant and atrioventricular reentrant tachycardias with extremely high success rates. The suitability of catheter ablation for treatment of atrial tachycardia, a much less common type of supraventricular tachycardia, has not been well addressed. Fifteen patients (8 females) ranging from 10 to 83 years (mean 38 +/- 22) were referred for catheter ablation of supraventricular tachycardia. The diagnosis of atrial tachycardia was established by standard electrophysiologic techniques. A combination of activation and pace mapping was used to identify a suitable site for radiofrequency current catheter ablation. Medical therapy was unsuccessful in all but 1 patient. Two patients had surgically corrected congenital heart disease, 2 had coronary artery disease and 1 had dilated cardiomyopathy. Seven patients had depressed left ventricular function. Six patients had incessant tachycardias. Presumed tachycardia mechanism was automatic in 11 patients and reentrant in 4. Mean tachycardia cycle length was 372 +/- 74 ms. Catheter ablation was acutely successful in 12 patients (80%) with application of 11.1 +/- 6.6 lesions at a mean voltage of 60 +/- 9 V. In the other 3 patients, 16 to 38 lesions were applied. At a mean follow-up of 18.5 +/- 6.5 months, 2 patients have had recurrences with different P-wave morphologies and underwent a second successful catheter ablation procedure. An additional 2 patients had recurrences with the same P-wave morphology and 1 underwent a second successful catheter ablation procedure. Thus, radiofrequency ablation can be used in a diverse population of patients with atrial tachycardia with an acute success rate of 80% and a long-term success rate of 73%. PMID- 8213511 TI - Comparison of effects of felodipine versus hydrochlorothiazide on arterial diameter and pulse-wave velocity in essential hypertension. AB - In a double-blind cross-over study, the arterial changes produced by hydrochlorothiazide were compared with those observed after the calcium antagonist felodipine in 16 patients with mild to moderate systemic hypertension. Diameter changes at the site of the common carotid and brachial arteries were investigated using pulsed Doppler velocimetry, and pulse-wave velocities of the aortic, brachial and femorotibial areas were measured using standard noninvasive techniques. Whereas hydrochlorothiazide and felodipine similarly decreased blood pressure, hydrochlorothiazide did not change pulse-wave velocity, and the diameters of the brachial and common carotid arteries. Felodipine significantly decreased pulse-wave velocity, and increased brachial arterial diameter and compliance, with no change in carotid arterial diameter. Evidence was found that although felodipine had specific effects on the arterial system of hypertensive subjects, hydrochlorothiazide did not produce any sizable arterial change. These differential effects may influence specifically the heart afterload, with important consequences for diuretics that are known to cause minimal changes in cardiac structure and function. PMID- 8213512 TI - Comparison of single-dose nifedipine and captopril for chronic severe aortic regurgitation. AB - The effects of a single dose of either nifedipine 20 mg (n = 10) or captopril 50 mg (n = 10) were compared in 20 patients with symptomatic, chronic severe aortic regurgitation using angiography and micromanometer left ventricular pressure measurements. At 90 minutes, mean arterial pressure was reduced comparably after both drugs (86 +/- 15 to 76 +/- 18 mm Hg for nifedipine vs 95 +/- 19 to 77 +/- 18 mm Hg for captopril, p = NS between groups by analysis of variance), as was wedge pressure (11 +/- 5 to 9 +/- 4 mm Hg vs 13 +/- 9 to 9 +/- 5 mm Hg for captopril). Systemic vascular resistance was reduced more (p = 0.01) after nifedipine than after captopril (1,549 +/- 468 to 1,067 +/- 291 dynes s cm-5 vs 1,632 +/- 559 to 1,436 +/- 392 dynes s cm-5). Heart rate declined after captopril (84 +/- 14/min to 75 +/- 15/min, p = 0.002) but not after nifedipine (78 +/- 13 min to 80 +/- 14 min). Forward stroke volume increased after nifedipine (58 +/- 14 to 70 +/- 16 ml, p < 0.001) but not after captopril (58 +/- 17 to 59 +/- 16 ml). Thus, cardiac output increased after nifedipine (4.4 +/- 0.9 to 5.5 +/- 1.2 liters/min, p < 0.001) but decreased after captopril (4.8 +/- 1.2 to 4.3 +/- 1.0, p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213513 TI - Assessment of intracoronary morphology in cardiac transplant recipients by angioscopy and intravascular ultrasound. AB - Percutaneous coronary angioscopy and intravascular ultrasound are sensitive intravascular imaging methods for detecting early changes in coronary morphology in cardiac transplant recipients. To compare the 2 imaging modalities, 29 consecutive cardiac transplant recipients underwent percutaneous coronary angioscopy and intravascular ultrasound during annual coronary angiography. Surface morphology, presence of plaque, and percent area stenosis were determined with each procedure. Percutaneous coronary angioscopy was more sensitive in detecting the presence of plaque and stenosis than was coronary angiography (plaque: 79 vs 10% [p < 0.001]; and stenosis: 24 vs 3% [p < 0.01]). Intravascular ultrasound was also more sensitive in detecting plaque (76 vs 10%; p < 0.001) and stenosis (45 vs 3%; p < 0.001) than was coronary angiography. Although both angioscopy and ultrasound identified atherosclerotic plaque, only percutaneous coronary angioscopy could show luminal surface morphology and pigmentation of the plaque. Conversely, ultrasound could detect calcification and presence of intimal thickening, and was more accurate in assessing the severity of stenosis (45 vs 24%; p < 0.01). In conclusion, percutaneous coronary angioscopy and intravascular ultrasound, in conjunction, provide information not only regarding the appearance of the luminal surface, but also quantitative information regarding the structure and extent of the disease in the coronary artery wall. PMID- 8213514 TI - Comparison of left ventricular function by echocardiographic automated border detection and by radionuclide ejection fraction. AB - Echocardiographic automated border detection can provide on-line estimates of left ventricular cavity area by differentiating blood from tissue backscatter characteristics. The objective of this study was to assess the ability of short axis measurements of left ventricular cavity area by automated border detection to determine left ventricular function by comparing these measurements to radionuclide measures of ejection fraction in the same patients. Eighty-eight consecutive patients, aged 53 +/- 14 years, underwent automated border detection studies within 2 hours of radionuclide ventriculography. Short-axis imaging with automated border detection was attempted at basal, midpapillary muscle, and apical levels. Maximal left ventricular length was also measured from apical 4- and 2-chamber views by standard imaging. Fractional area change--(end-diastolic area-end-systolic area)/end-diastolic area--was determined at each short-axis level. Volumes and ejection fractions were calculated using: volume = 5/6 (midventricular area).length. Simpson's rule for 3 short-axis measurements was calculated using: volume = (length/12) (5.basal area + 2.mid-area + 4.apical area). Technically adequate automated border detection data could be obtained on 69 patients (78%) at basal and mid-levels, and at all 3 short-axis levels in 66 patients (75%). Correlations with radionuclide ejection fraction were as follows: midventricular fractional area change--R = 0.84, SEE = 12%, y = 0.86 x - 7; area length ejection fraction--R = 0.89, SEE = 9%, y = 0.96 x - 4; and Simpson's rule- R = 0.91, SEE = 8%, y = 0.89 x + 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213515 TI - Improvisation in implantable medical devices: a Gordian knot. PMID- 8213516 TI - Are all calcium antagonists equally effective for reducing reinfarction rate? PMID- 8213517 TI - Prediction of the level of left anterior descending coronary artery obstruction during anterior wall acute myocardial infarction by the admission electrocardiogram. PMID- 8213518 TI - Clinical and angiographic correlates of in-hospital death after percutaneous transluminal coronary angioplasty for conditions other than acute myocardial infarction. PMID- 8213519 TI - Hemoperfusion during right coronary artery angioplasty causing high-grade heart block. PMID- 8213520 TI - Heightened free radical activity in angina pectoris. PMID- 8213521 TI - Prognostic significance of second-degree atrioventricular block in inferior wall acute myocardial infarction. SPRINT Study Group. PMID- 8213522 TI - Sensitivity in detecting drug-induced alterations in the PR interval: comparison of the surface electrocardiogram measured by a cardiologist versus routine automated computer analysis. PMID- 8213523 TI - Evaluation of an abbreviated protocol for catheter ablation of left free wall accessory pathways. PMID- 8213524 TI - Effect of pregnancy on paroxysmal supraventricular tachycardia. PMID- 8213525 TI - Mitral regurgitation associated with reduced thromboembolic events in high-risk patients with nonrheumatic atrial fibrillation. Stroke Prevention in Atrial Fibrillation Investigators. PMID- 8213526 TI - Early recurrence of accessory pathways after radiofrequency catheter ablation does not preclude long-term cure. PMID- 8213527 TI - Prognosis of congestive heart failure in patients aged > or = 62 years with unoperated severe valvular aortic stenosis. PMID- 8213528 TI - Prevalence and clinical significance of mild paraprosthetic ring leaks and left atrial spontaneous echo contrast detected on transesophageal echocardiography three months after isolated mitral valve replacement with a mechanical prosthesis. PMID- 8213529 TI - Balloon mitral valvotomy for rheumatic mitral stenosis in children aged < or = 12 years. PMID- 8213530 TI - Usefulness of intracardiac echocardiography in transseptal puncture during percutaneous transvenous mitral commissurotomy. PMID- 8213531 TI - Usefulness of technetium-99m pyrophosphate myocardial scintigraphy in amyloid polyneuropathy and correlation with echocardiography. PMID- 8213532 TI - Subpectoral implantation of cardioverter-defibrillator combined with a nonepicardial lead system: preliminary experience with a novel approach. PMID- 8213533 TI - Earlobes, obesity and bias in observational studies. PMID- 8213534 TI - More on the diagonal earlobe crease as a marker of coronary artery disease. PMID- 8213535 TI - Is the site of maximal coronary artery narrowing the culprit for future myocardial infarction? PMID- 8213536 TI - Granular cell tumor with symptomatic cardiac involvement can be malignant or benign. PMID- 8213537 TI - Relation between patent foramen ovale and stroke. PMID- 8213538 TI - Polymorphous ventricular tachycardia early after acute myocardial infarction. PMID- 8213539 TI - Prognostic significance and the role of dual-chamber pacing in atrioventricular delay in idiopathic dilated cardiomyopathy. PMID- 8213540 TI - Comparison of dobutamine stress echocardiography, dipyridamole stress echocardiography and exercise stress testing for diagnosis of coronary artery disease. AB - To compare the value of dobutamine and dipyridamole stress echocardiography with exercise stress testing for the diagnosis of coronary artery disease (CAD), 80 patients with chest pain of suspected myocardial ischemic origin (57 with CAD and 23 without significant CAD) underwent dobutamine stress echocardiography (5 to 40 micrograms/kg/min), dipyridamole echocardiography (0.84 mg/kg over 10 minutes) and bicycle exercise electrocardiography after discontinuation of antianginal treatment. Dobutamine echocardiography and exercise testing revealed a higher overall sensitivity than dipyridamole echocardiography (79 vs 60%, p < 0.005; 77 vs 60%, p < 0.05, respectively); this finding was due to a higher dobutamine and exercise sensitivity in 1-vessel CAD (62 vs 33%, p < 0.05 for both tests), whereas sensitivity of the 3 tests was similar in multivessel CAD. Dobutamine and dipyridamole showed a higher specificity than exercise (83 vs 43%, p < 0.01; 96 vs 43%, p < 0.005, respectively). Diagnostic accuracy of dobutamine echocardiography was higher than that of exercise (80 vs 67%, p < 0.05), whereas the difference with dipyridamole (80 vs 70%) was not significant. In the tests that yielded positive results, double product during exercise was significantly higher than that during dobutamine and dipyridamole echocardiography. No major complications occurred during the tests, but adverse effects were more frequent during dobutamine testing. Thus, dobutamine echocardiography may be superior to dipyridamole echocardiography and exercise electrocardiography for the diagnosis of CAD. PMID- 8213541 TI - Eccentric dosing with isosorbide-5-mononitrate in angina pectoris. AB - In a placebo-controlled, parallel, double-blind study, 214 patients with stable angina were studied. Doses of 5, 10 and 20 mg of immediate-release isosorbide-5 mononitrate (IS-5-MN) or placebo were administered at 0800 and 1500 hours for a period of 3 weeks. On days 1 and 14, patients underwent exercise testing before, and 2 and 7 hours after both doses; on days 7 and 21, testing was performed 2 hours after morning dosing. Study variables included total exercise duration and time to moderate angina. On day 1, the active treatment groups showed improvement over the placebo group 2 and 7 hours after dose 1, and 2 hours after dose 2. Throughout the subsequent study period, each active treatment group was superior to placebo 2 hours after the first and second doses. Only the 20 mg dose increased exercise duration 7 hours after dosing, and this was observed after both doses 1 and 2 on day 14. There were fewer episodes of angina in patients receiving the 20 mg dose. There was no increase in nocturnal angina during eccentric dosing with IS-5-MN. In comparing exercise times throughout the study, tolerance did not develop during eccentric dosing. The morning exercise tests before tablet administration showed a progressive increase during the study period, with slightly greater improvement in patients receiving active therapy. This absence of a zero hour effect suggests that rebound does not occur during eccentric dosing with immediate-release IS-5-MN. PMID- 8213542 TI - Hospital mortality in acute myocardial infarction in the era of reperfusion therapy (the Myocardial Infarction Triage and Intervention Project). AB - This study was conducted in 19 hospitals in the metropolitan Seattle area and included 6,270 unselected patients who had acute myocardial infarction (AMI) between January 1988 and April 1991. Hospital mortality was determined and related to patient demographic and clinical characteristics, the use of reperfusion therapies, and to complications after AMI. Thrombolytic therapy or direct coronary angioplasty < 6 hours from symptom onset was used to treat 1,185 (19%) and 524 (9%) patients, respectively. There were 629 (10%) hospital deaths; most occurred during the first 3 days of hospitalization. Factors affecting mortality after admission included: recurrent chest pain, recurrent AMI, development of heart failure, and the occurrence of stroke. After adjustment for age, treatment with thrombolytic therapy or direct angioplasty had no independent effect on reducing the overall mortality rate. Hospital mortality rates for AMI have improved considerably since 1970, although recurrent myocardial ischemic events continue to have an adverse effect on outcome. The current use of reperfusion treatments has had minimal causal impact on overall mortality rates, principally because less than one third of patients, who are relatively "low risk," are eligible and receive these treatments. PMID- 8213543 TI - Predictors and long-term prognostic significance of recurrent infarction in the year after a first myocardial infarction. SPRINT Study Group. AB - This study was undertaken to examine whether clinical factors predict reinfarction within 1 year of a first acute myocardial infarction (AMI) and to quantify the subsequent influence of reinfarction on long-term mortality. Data from 3,695 patients with a first AMI included in the Secondary Prevention Reinfarction Israeli Nifedipine Trial Registry were analyzed. The 1-year reinfarction incidence was 6.0% (220 of 3,695) and in-hospital mortality during reinfarction was 31%. Patients with reinfarction were older (63.0 vs 60.8 years) at entry. The independent clinical predictors for 1-year reinfarction were (adjusted relative odds): peripheral vascular disease (2.12), anterior location of the first AMI (1.62), angina before the first AMI (1.53), congestive heart failure on admission (1.34), diabetes (1.33), systemic hypertension (1.28) and age increment (1.13). One-year reinfarction rate increased from 4.0% in patients with 0 or 1 risk factor to 23.3% in patients with 5 to 6 risk factors (p < 0.0001). Patients with reinfarction had significantly increased 1- and 5-year mortality compared with those who had no reinfarction (11.8 vs 5.3% and 40.1 vs 20.3%, respectively, p < 0.001). Recurrent AMI within 1 year was the most powerful predictor of long-term (mean 5.5 years) total mortality (adjusted relative risk = 4.76). PMID- 8213544 TI - Usefulness of Holter monitoring for detecting myocardial ischemia in patients with nondiagnostic exercise treadmill test. AB - To determine if Holter monitoring can predict cardiac risk in patients when the exercise test is nondiagnostic, a total of 90 eligible patients were monitored for 24 hours after their exercise test without alterations in baseline medications. Prospective follow-up was obtained and events were confirmed by investigators unaware of subjects' clinical data. Nineteen patients (21%) had a total of 71 episodes of ST depression, all of which were asymptomatic. During a mean follow-up of 719 days, there were 10 patients with adverse events: 3 with cardiac deaths, 3 with nonfatal myocardial infarctions, and 4 with admissions for unstable angina. Of the 10 adverse events, 9 occurred in the group of 19 with ST depression detected by Holter (relative risk 34, 95% confidence interval 10 to 114). The sensitivity of ST depression was 90%, the specificity 88%, the predictive positive value 47%, and the predictive negative value 99%. In a multivariate Cox proportional-hazards model that controlled for prior history of coronary artery disease, hypercholesterolemia, and all exercise test variables, the presence of ST depression detected by Holter was the only independent predictor of outcome. In patients with nondiagnostic exercise tests, ST depression detected by Holter monitoring identified those with an increased risk of adverse cardiac events. The absence of ST depression detected by Holter was a useful predictor of low risk. PMID- 8213545 TI - Infrared thermography in the detection and management of coronary artery disease. AB - Infrared thermography was used to measure and map precordial skin temperature in 60 patients undergoing elective coronary angiography; 9 patients were normal and 51 had coronary artery disease (CAD). Thermograms were graded by quartile area (zero to 4 plus) and magnitude of thermal asymmetry (recorded as degrees celsius). The presence, mean area and degree of thermal asymmetry were significantly greater in patients with CAD. Twenty-two patients subsequently underwent successful revascularization with angioplasty with a highly significant decrease in the presence, magnitude and degree of thermal asymmetry. The results demonstrate that CAD is associated with precordial thermal asymmetry. The area and magnitude of thermal asymmetry is greater in patients with CAD than in control subjects without angiographically significant CAD. Successful revascularization changed the asymmetric precordial pattern to a more symmetric one. Infrared thermography is a promising technique for the detection of CAD before and after revascularization. PMID- 8213546 TI - Short-term heart rate variability and factors modifying the risk of coronary artery disease in a population sample. AB - Heart rate (HR) variability is impaired in chronic coronary artery disease (CAD), but the mechanism is not fully resolved. This study was aimed at assessing whether HR variability is influenced by the risk factors of CAD. Of a random sample of 120 subjects born in 1954, 88 (41 men and 47 women) could be included in the analyses. No subject had clinical heart disease. The subjects' physical activity, alcohol consumption and smoking were quantified by 2-month diary follow up. Serum lipids and insulin were measured. The tests of HR variability included power spectral analysis and calculation of the root-mean-square difference of RR intervals at rest under controlled respiration. HR variability indexes were asymmetrically distributed and strongly HR-dependent, and therefore, all statistical tests were performed on log-transformed data adjusted to the population mean HR. Multiple regression analyses showed independent inverse relations between the root-mean-square RR difference and low-density lipoprotein (LDL) cholesterol (beta = -0.22; p = 0.008), and between the total RR-interval power and LDL cholesterol (beta = -0.25; p = 0.007), as well as smoking (beta = 0.19; p = 0.035). In women, alcohol use influenced the RR-interval root-mean square difference (beta = 0.31; p = 0.015), total power (beta = 0.33; p = 0.017) and high-frequency power (beta = 0.26; p = 0.056). It is concluded that short term HR variability is related inversely to LDL cholesterol and smoking in the population, and directly to alcohol use in women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213547 TI - Effects of percutaneous transluminal coronary angioplasty balloon compliance on angiographic and clinical outcomes. AB - The effect of balloon compliance on the safety and outcome of percutaneous transluminal coronary angioplasty (PTCA) is controversial. It has been proposed that PTCA balloons constructed from compliant polymers contribute to an increased risk of angiographic coronary dissection and potentially to adverse clinical results. To determine the effect of balloon material compliance on PTCA outcome, 1,076 PTCA procedures using balloons differing in compliance characteristics (polyethylene teraphthalate [noncompliant], polyethylene [intermediately compliant] or polyolefincopolymer [compliant]) were retrospectively analyzed. Baseline clinical, angiographic and procedural variables were similar among the 3 balloon material groups. In the noncompliant, intermediately compliant and compliant groups, the occurrence rates of intimal tears (10, 14 and 10%, respectively; p = NS for all comparisons) and coronary dissection (7, 9 and 8%, respectively; all p = NS) were also equivalent. The rates of acute occlusion, myocardial infarction, emergency bypass surgery and death were low and similar, and likewise unaffected by balloon material. The results provide evidence that the occurrence of adverse outcomes after PTCA is unrelated to balloon material compliance and support the clinical safety of balloons constructed of compliant or noncompliant polymers when used for appropriate coronary interventions. PMID- 8213548 TI - Outcome with implantable cardioverter-defibrillator therapy for survivors of ventricular fibrillation secondary to idiopathic dilated cardiomyopathy or coronary artery disease without myocardial infarction. AB - Patients with idiopathic dilated cardiomyopathy (IDC) constitute a minority among implantable cardioverter-defibrillator (ICD) recipients; how these patients fare versus those with coronary artery disease (CAD) is not well defined, nor is the mechanism of cardiac arrest recurrence, which may involve a more significant role of bradyarrhythmias. A retrospective multicenter study regarding outcome of ICD therapy was conducted in 224 patients with either IDC (n = 69; 31%) or CAD (n = 155; 69%) presenting exclusively with ventricular fibrillation (VF) unassociated with acute myocardial infarction. Patients with IDC were significantly younger (mean age 57 vs 61 years in patients with CAD, p < 0.04) and less male predominant (64 vs 79% in patients with CAD, p < 0.02). There was no significant difference in mean left ventricular ejection fraction (0.27 in IDC patients vs 0.29 in CAD patients), but sustained ventricular tachycardia was induced less often in patients with IDC (21 vs 58% in CAD patients, p < 0.001). Bradycardia pacing, either by an ICD with bradycardia pacing ability or a separate bradycardia pacemaker, was available in only 15% of ICD implantees. During a median follow-up duration of 1.7 years for patients with IDC and 1.9 years for patients with CAD, estimated cumulative event rates were similar for any type shock (2-year incidence of 74% in IDC patients, 69% in CAD patients) as well as for appropriate shock (2-year incidence of 46% in IDC patients, 40% in CAD patients).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213549 TI - Frequency of presumed reentry with an excitable gap in sustained ventricular tachycardia unassociated with coronary artery disease. AB - In sustained ventricular tachycardia (VT) unrelated to coronary artery disease, the incidence of reentry with an excitable gap was examined, and rapid pacing was performed to entrain VT in 48 episodes in 42 consecutive patients. Coronary artery disease was excluded by coronary arteriography. The underlying heart diseases were postoperative congenital heart diseases (n = 5), dilated (n = 7) or hypertrophic (n = 4) cardiomyopathy, arrhythmogenic right ventricular dysplasia (n = 6) and miscellaneous heart diseases (n = 5), as well as no demonstrable heart disease (n = 15) in which 8 patients had verapamil-responsive VT. Except for 1 patient with hypertrophic cardiomyopathy, 48 morphologically distinct monomorphic sustained VTs were induced. Twenty-five VTs showed right bundle branch block morphology and 23 left bundle branch block morphology, and VT was entrained in 84 and 96%, respectively. The overall incidence of the entrainment was 89.6% (43 of 48 monomorphic VTs), and the frequency of the ability to entrain VT ranged between 33.3 and 100% in the subgroups. The lowest frequency was found in hypertrophic cardiomyopathy. In conclusion, most inducible monomorphic sustained VT unassociated with coronary artery disease was presumed to be reentry with an excitable gap. PMID- 8213550 TI - Usefulness of transesophageal pacing during exercise for evaluating palpitations in top-level athletes. AB - The aim of this study was to verify the use of transesophageal atrial pacing in reproducing tachyarrhythmias in 22 top-level athletes symptomatic for palpitations, with no evidence of arrhythmias or cardiac anomalies by the standard noninvasive diagnostic techniques. The transesophageal stimulation protocol was divided in 2 sections: at rest and during exercise on the bicycle ergometer in the upright position. Although transesophageal pacing at rest did not induce any arrhythmias in 18 of 22 athletes, during exercise it induced tachyarrhythmias. This occurred in all 16 athletes who had palpitations during physical activity. Electrophysiologic characteristics of induced atrial tachyarrhythmia suggested reentry within the atrioventricular node in 9 of 18 athletes: atrial fibrillation in 5, atrial flutter in 2, orthodromic reciprocating tachycardia due to concealed anomalous pathway in 1, and automatic atrial tachycardia in 1. This study stresses the clinical importance of palpitations during physical exercise and shows that transesophageal pacing performed during exercise is an important diagnostic tool in reproducing the previously described symptoms and in detecting the underlying tachyarrhythmias. PMID- 8213551 TI - Acute and delayed hormonal changes in mitral stenosis treated by balloon valvulotomy. AB - The role of left atrial and aortic pressures on the secretion of the main hormones controlling blood volume is still subject to debate in humans. Because of increased mean left atrial pressure and decreased mean aortic pressure produced by balloon inflation in patients with mitral stenosis treated with balloon valvulotomy, the hormonal changes occurring acutely (group II of patients) were measured. The same studies (group I patients) were also performed 48 hours after this treatment, a period at which left atrial pressure permanently diminished. Inflation of the balloon resulted in a decrease in plasma renin activity and increases in plasma atrial natriuretic factor (ANF) and plasma arginine vasopressin (AVP). Forty-eight hours after balloon valvulotomy, which had produced a decrease in left atrial pressure, plasma ANF was lower (58.9 +/- 7.9 vs 95.3 +/- 11.9 pg/ml; p < 0.001), and plasma renin activity (2,575 +/- 533 vs 960 +/- 113 pg/ml/hour; p < 0.01), plasma angiotensin II (25.0 +/- 4.1 vs 9.3 +/- 1.3 pg/ml; p < 0.001) and plasma aldosterone (181.7 +/- 36.7 vs 139.9 +/- 19.8 pg/ml; p < 0.05) were higher than their respective control levels 24 hours before treatment of the stenosis. In contrast, plasma AVP (3.7 +/- 0.25 vs 4.4 +/ 0.31 pg/ml; p = 0.001) diminished moderately along with plasma osmolality (282.4 +/- 0.1 vs 286.2 +/- 0.6 mOsm/kg; p < 0.001). Urinary sodium excretion was also examined before and after balloon valvulotomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213552 TI - Prognosis in hypertrophic cardiomyopathy observed in a large clinic population. AB - Overall annual cardiac mortality in hypertrophic cardiomyopathy (HC) has been reported to be between 2 and 4%, although these numbers are primarily from retrospective studies of patients referred to large research institutions. A clinic population of 113 patients with HC was prospectively studied to assess cardiac mortality in the overall group and in selected subgroups commonly thought to be at high risk for sudden death. The mean age at diagnosis was 37 +/- 16 years. During follow-up, there were 11 cardiac and 2 noncardiac deaths. The annual cardiac mortality was 1% (95% confidence interval 0.2-1.8%). Because of the small number of deaths, relative risk for cardiac death was not significantly different in the presence of young age (< or = 30 years), family history of HC and sudden death, history of syncope or previous cardiac arrest, or both, ventricular tachycardia on 24-hour Holter monitoring, or septal myotomy/myectomy for refractory symptoms and outflow tract obstruction. It is concluded that HC has a relatively benign prognosis (1% annual cardiac mortality) that is 2 to 4 times less than that previously reported. PMID- 8213553 TI - Comparison of morphologic findings in spontaneously occurring hypertrophic cardiomyopathy in humans, cats and dogs. AB - Morphologic features of spontaneously occurring hypertrophic cardiomyopathy (HC) were compared in 38 humans, 51 cats and 10 dogs. Asymmetric hypertrophy of the ventricular septum, marked disorganization of cardiac muscle cells, abnormal intramural coronary arteries and myocardial fibrosis were each present in the ventricular septum of human, feline, and canine forms of HC; these abnormalities were generally more severe and most frequently identified in humans. Asymmetric left ventricular hypertrophy (based on the calculated septal-to-free wall thickness ratio) was most common in humans (31 of 38 [81%]) and dogs (8 of 10 [80%]), as compared with cats (16 of 51 [31%]; p < 0.001) with HC; in all 3 species, hypertrophy was often diffuse, involving substantial portions of the anterolateral and posterior free walls, and the ventricular septum. Marked septal disorganization (> or = 5% of the tissue section) was present in 35 patients (92%), but in only 14 cats (27%) and 2 dogs (20%) (p < 0.001). Abnormal intramural coronary arteries occurred with similar frequency in the ventricular septum of patients (n = 25; 66%), cats (n = 38; 74%) and dogs (n = 6; 60%) (p < NS). Moderate-to-severe septal fibrosis was identified more commonly in humans (15 of 38 [39%]) than in animals (13 of 61 [21%]; p < 0.001). In all 3 species, abnormal intramural coronary arteries were most commonly observed within or at the margins of areas of fibrous tissue. These morphologic findings describe spontaneously occurring models of HC in cats and dogs with substantial structural similarities to the well-recognized disease entity in humans. PMID- 8213554 TI - Gross and semiquantitative histologic findings in mononuclear cell myocarditis causing sudden death, and implications for endomyocardial biopsy. AB - The distribution of gross myocardial lesions and the relative density of the inflammatory cells in various myocardial locations (subepicardial and subendocardial halves of the left ventricular free wall, right ventricular and left ventricular halves of the ventricular septum, and the right ventricular free wall) were studied in 14 patients (11 male [79%], 8 black [57%], aged 7 months to 65 years [median 16 years]) who died suddenly of acute mononuclear-cell myocarditis. Grossly visible myocardial lesions were present in 8 patients, and preferentially involved the subepicardial regions of the left ventricular free wall. The highest mean number of mononuclear cells were seen in the subepicardial regions of the left ventricular free wall (193 cells per high-power field) and the lowest in the right ventricular one half of the ventricular septum (92 cells per high-power field, p < 0.001). Thus the predominant location of the gross myocardial lesions in acute mononuclear-cell myocarditis is the subepicardial region of the left ventricular free wall. A relatively low density of mononuclear cells are found in the right ventricular half of the ventricular septum, the main location of endomyocardial biopsies. PMID- 8213555 TI - Predicting hospital charge and length of stay for congenital heart disease surgery. AB - Three hundred twenty-two consecutive operations between December 1985 and December 1989 for 10 types of low-risk congenital cardiac malformations were reviewed to determine the hospital charge and postoperative length of stay. Multiple regression analysis of variance was used to predict the influence of the primary diagnosis and various preoperative parameters. The average hospital charge was $27,262 +/- $20,644 and the postoperative length of stay was 9.3 +/- 8.3 days. Age at operation alone did not influence the dependent variables. The diagnosis of atrial septal defect (p = 0.002) or coarctation of the aorta (p = 0.002) decreased the mean charge, whereas the 8 other primary diagnoses did not significantly influence the mean charge. Other preoperative factors found to be predictive of increased hospital charge were: the date of operation (p < 0.001), cyanosis (p = 0.008), previous thoracic surgery (p = 0.02), failure to thrive (p < 0.001), associated major extra cardiac anomalies (p < 0.001), oxygen requirement (p = 0.02), and distance > 100 miles from home to hospital (p = 0.05). A primary diagnosis of atrial septal defect decreased the mean postoperative length of stay by 3.1 days (p < 0.001). Other preoperative conditions increased the mean postoperative length of stay: major extracardiac malformation (p < 0.001), failure to thrive (p < 0.001), and oxygen requirement (p = 0.003). Charge and length of stay equations were generated which may assist in the prediction of resource utilization in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213556 TI - Value of the 12-lead electrocardiogram in arrhythmogenic right ventricular dysplasia, and absence of correlation with echocardiographic findings. AB - The 12-lead electrocardiogram during sinus rhythm was studied in 20 patients with arrhythmogenic right ventricular (RV) dysplasia with symptomatic ventricular tachycardia. Findings were analyzed, together with echocardiographic evaluation of site, extent and progression of RV wall abnormalities. Electrocardiographic abnormalities were found in 90% of patients. No correlation was found between abnormalities on the initial 12-lead electrocardiogram, and the echocardiographic extent and location of RV involvement. Over time, echocardiographic progression of the disease was observed; RV size increased in 6 of 7 patients from 34 +/- 3 to 39 +/- 3 mm (p = 0.01), and there was progression in the extent of RV wall motion abnormalities in 4 of 7 patients. Analysis of serial electrocardiographic recordings did not reveal changes indicative of progression of the disease during follow-up of 71 +/- 48 months. It is concluded that electrocardiographic abnormalities suggesting arrhythmogenic RV dysplasia are present in 90% of symptomatic patients on the first electrocardiogram recorded during sinus rhythm. However, serial electrocardiographic recordings in these patients do not provide information regarding anatomic progression of the disease. PMID- 8213557 TI - Cardiovascular medicine: subspecialty or specialty. PMID- 8213558 TI - Impact of patient selection biases on the perception of hypertrophic cardiomyopathy and its natural history. PMID- 8213559 TI - Comparison of QT dispersion in hypertrophic cardiomyopathy between patients with and without ventricular arrhythmias and sudden death. PMID- 8213560 TI - Tricuspid valve regurgitation as a complication of pulmonary balloon valvuloplasty or transcatheter closure of patent ductus arteriosus in children < or = 4 years of age. PMID- 8213561 TI - Prospective echocardiographic screening for coronary artery anomalies in 1,360 elite competitive athletes. PMID- 8213562 TI - Effects of smoking cessation on blood pressure. PMID- 8213563 TI - The future of directional coronary atherectomy. PMID- 8213564 TI - Experience with directional coronary atherectomy since pre-market approval. AB - Directional coronary atherectomy (DCA) received Food and Drug Administration (FDA) Pre-Market Approval in September 1990 and was then released through formal training certification of physicians at each new site. Procedure volume has increased dramatically since approval, with > 17,000 DCA procedures performed in 1991 and a cumulative total of > 33,000 procedures by mid-1992, at > 670 centers in the United States. Clinical application and results since approval have generally been similar to preapproval multicenter investigational results. Comparison of pre- and postapproval usage at the Medical College of Virginia shows similar baseline characteristics and indications, although recent patients show a higher proportion of "salvage" DCA for failed or suboptimal angioplasty (6% vs 14%) or DCA in combination with multidevice multiple vessel intervention (30% vs 38%). Overall results in 300 patients and 345 procedures included procedural success in 95%, clinical success in 94%, with major complications in 4.6% (including urgent bypass surgery in 3.8%, Q wave myocardial infarction in 1.7%, and hospital mortality in 0.3%). Results before and after FDA approval were similar for procedural success (94% vs 96%), clinical success rate (94% vs 94%), and major complications (5.5% vs 4.4%). There was a trend toward lower urgent surgery rate (5.4% vs 3.3%) in the more recent experience. In addition to its established efficacy for highly eccentric lesions, newer applications for which DCA is being used following FDA approval include treatment of saphenous vein grafts, thrombus-associated lesions, aorto-ostial lesions, failed or suboptimal percutaneous transluminal coronary angioplasty result, bifurcation lesions, and use as part of multivessel intervention.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213565 TI - Indications for directional coronary atherectomy: 1993. AB - New coronary devices are being developed in attempts to solve the limitations of balloon angioplasty. Directional coronary atherectomy was the first of these devices to gain Food and Drug Administration approval. Theoretically, directional atherectomy improves coronary stenoses by an entirely different mechanism than balloon angioplasty, removing atherosclerotic plaque and leaving a smooth surface with less elastic recoil. Nonrandomized experience has shown that directional atherectomy is most useful in proximal to mid-segment, noncalcified, large (> 2.5 mm) coronary arterial segments, yielding minimal residual stenosis and larger lumen diameters than are generally achieved with angioplasty. Experience suggests that directional atherectomy is most useful in ostial coronary lesions, bifurcation stenoses, proximal left anterior descending lesions, discrete saphenous vein graft stenoses, complex or thrombus-containing lesions, highly eccentric lesions, and lesions failing PTCA secondary to elastic recoil, recurrent thrombosis, or limited dissection. Dissection and out-of catheterization-laboratory acute closure are infrequent and appear to be improved over balloon angioplasty. However, intimal hyperplasia leading to restenosis is not solved by directional atherectomy. Randomized studies such as the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT) will help to clarify further the overall utility of directional atherectomy compared with balloon angioplasty in the future, but due to the limited power of subgroup analyses, CAVEAT may not have fully defined all the specific lesion characteristics that may be improved by atherectomy over PTCA. Review of the data presented may help the clinician identify specific areas in which atherectomy appears to offer an advantage over angioplasty, although definitive answers await specifically targeted randomized trials. PMID- 8213566 TI - How atherectomy began: a personal history. PMID- 8213567 TI - Directional coronary atherectomy of saphenous vein graft narrowings: multicenter investigational experience. AB - Directional coronary atherectomy (DCA) of saphenous vein graft lesions was performed at 21 centers between June 1988 and September 1990, which represents the multicenter investigational experience. A total of 318 procedures were performed and 363 vein graft lesions were treated. Angiographic success with DCA was achieved in 86% of lesions and clinical success was achieved in 85% (269 of 318) of patients. Major complications occurred in 2.5% of patients, with Q wave myocardial infarction (MI) in 1.3%, death in 0.9%, and urgent bypass surgery in 0.9%. Other complications included non-Q wave MI in 4.4%, distal embolization in 7.2%, coronary occlusion in 1.9%, and vessel perforation in 0.6%. Although there was a trend toward lower success rates with ostial vein graft lesions (82% vs 88% for other graft sites) and with diffuse (length > 20 mm) graft lesions (75% vs 87% for shorter lesions), the differences were not significant. Baseline clinical and angiographic factors did not identify predictors of lower success or more frequent complications in the study group. Overall restenosis rate in the 149 patients with angiographic restudy was 57%. The restenosis rate was significantly lower with primary vein graft lesions (38%) compared with a 75% restenosis rate for grafts with prior restenosis, p < 0.001. This initial multicenter investigational experience indicates that directional coronary atherectomy is a safe and effective therapy for selected saphenous vein graft disease. Although the overall restenosis rate is relatively high, the restenosis rate following DCA of primary vein graft lesions is significantly lower than for vein grafts having had prior intervention.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213568 TI - Specific indications for directional coronary atherectomy: origin left anterior descending coronary artery and bifurcation lesions. AB - Directional coronary atherectomy is emerging as the treatment of choice for many patients with significant lesions involving left anterior descending coronary artery origin or vessel bifurcations. It offers the potential advantages of safe, reliable, and predictable treatment of these selected complex lesions. Future modifications and improvements in the design of the atherectomy device (AtheroCath; Devices for Vascular Intervention, Redwood City, CA) may further expand its application to smaller and calcified vessels. PMID- 8213569 TI - Multicenter clinical experience with rescue atherectomy for failed angioplasty. AB - Directional coronary atherectomy (DCA) has been proposed as a "rescue" technique for failed or suboptimal percutaneous transluminal coronary angioplasty (PTCA) in an attempt to avoid myocardial infarction or emergency coronary artery bypass grafting. In this report we review the utilization and outcome of rescue atherectomy from the clinical experience of The Cleveland Clinic Foundation and Medical College of Virginia from November 1988 through January 1993, and from the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT) database. This analysis includes 100 patients with 103 treated lesions from 44 patients at the Cleveland Clinic, 36 patients from the Medical College of Virginia, and 20 patients from the CAVEAT database. The etiology of failed PTCA was primarily from dissection in 52 lesions (50.5%), "recoil" in 43 lesions (41.8%), and recurrent thrombosis in 8 lesions (7.8%). Complete vessel closure was present in 23 lesions (22.3%). The vessels treated included 51.5% left anterior descending, 24.3% right coronary, and 16.5% circumflex coronary arteries. The average reference vessel diameter in the group was 3.10 +/- 0.06 mm (SEM), with an average stenosis of 78.9 +/- 1.2% before PTCA, 55.8 +/- 2.4% after PTCA, and 24.1 +/- 2.2% after rescue DCA. DCA was successful (Thrombosis in Myocardial Infarction [TIMI] grade 3 flow with > 20% stenosis reduction without death, Q-wave myocardial infarction, or coronary artery bypass grafting) in 94 of 103 lesions (91.3%). Complications included 1 patient with perforation (1%), 2 deaths within 24 hours (2.0%), and 6 patients requiring coronary artery bypass grafting (6%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213570 TI - Complications of directional coronary atherectomy: incidence, causes, and management. AB - An assessment of complications is essential to the evaluation of directional coronary atherectomy. Major complications--such as death, Q wave myocardial infarction, or the need for emergency bypass surgery to correct acute vessel closure--result from a variety of familiar mechanisms, including dissection, thrombosis, or guiding catheter injury. In addition, unique complications of this device, such as catheter nose cone injury or vascular perforation, may also result in severe ischemia. With prompt recognition of the cause, most ischemic complications can be successfully treated in the catheterization laboratory. Less severe complications, such as femoral vascular injury, also require recognition and appropriate treatment in order to minimize sequelae. Although several large series have now documented that the overall incidence of atherectomy complications appears similar to that reported for conventional balloon angioplasty, no direct comparisons can be made until randomized trials (such as Coronary Angioplasty Versus Excisional Atherectomy Trial [CAVEAT]) are analyzed, to control for potential demographic or lesion-specific influences on complication rates. PMID- 8213571 TI - Clinical and angiographic outcome after directional coronary atherectomy. A qualitative and quantitative analysis using coronary arteriography and intravascular ultrasound. AB - To assess clinical and angiographic outcome after directional coronary atherectomy, the clinical course of 306 patients undergoing this procedure was reviewed. Directional atherectomy was successful in 290 (94.8%) procedures; complications developed in 8 (2.6%) patients. After atherectomy, percent diameter stenosis was reduced from 71 +/- 14 to 14 +/- 14% (p < 0.001) and minimal lumen diameter was increased from 0.87 +/- 0.42 to 2.55 +/- 0.57 mm (p < 0.001). In 128 (42%) patients, adjunct balloon angioplasty was performed to treat either complications or a residual stenosis > 30%. Intravascular ultrasound was also performed in 57 patients after directional atherectomy and demonstrated that a significant amount of residual plaque mass remained in lesions with a calcium arc > or = 90 degrees (17 +/- 5 mm2 vs 12 +/- 5 mm2 in lesions without calcium; p = 0.007). During the 11 +/- 6 month follow-up period, 69 (28.3%) patients developed recurrent clinical events (death, 5; Q wave myocardial infarction, 8; coronary bypass surgery, 31; coronary angioplasty, 36). Using a proportional hazards model, independent predictors of late clinical events included diabetes mellitus (relative risk [RR] = 1.95; p < 0.05), unstable angina (RR = 2.78; p < 0.005) and a prior history of restenosis (RR = 2.21; p < 0.01). We conclude that directional atherectomy is associated with high procedural success rates and infrequent complications in selected lesions subsets, although the degree of plaque resection may be limited if extensive calcium is present. Late clinical events develop in some (28%) patients after directional atherectomy, related to certain preprocedural clinical risk factors. PMID- 8213572 TI - Results of directional coronary atherectomy during multicenter preapproval testing. The US Directional Coronary Atherectomy Investigator Group. AB - Between 1988 and 1990, clinical testing was performed at 12 US institutions using the Simpson Coronary AtheroCath under an Investigational Device Exemption. Data on 1,069 lesions (873 patients) were analyzed and presented to the Food and Drug Administration (FDA) advisory panel in the summer of 1990, forming the basis for approval of this device in September 1990. Analysis of these preapproval data shows a primary success rate of 85% (defined as tissue removal, > or = 20% reduction in stenosis, < 50% residual stenosis after directional atherectomy, and no major complication), with somewhat higher primary success in prior restenosis and noncalcified lesions. Including the use of conventional angioplasty performed after atherectomy, the overall success rate was 92%. One or more major complications occurred in 4.9% of procedures, and included death (0.5%), nonfatal Q-wave myocardial infarction (0.9%), and emergency bypass surgery (4.0%). These complications were more frequent in right coronary, de novo, and diffuse (> 20-mm length) lesions. Six-month angiography results were available in 384 (77%) of 498 lesions eligible for follow-up when the registry closed and showed a restenosis rate (late stenosis > 50%) of 42%. The restenosis rate in both native vessels (30 vs 46%) and bypass grafts (31 vs 68%) was lower in primary (de novo) lesions compared with lesions that had developed restenosis after a prior intervention. Despite the use of prototype atherectomy catheters and still evolving procedural technique, this preapproval experience provided an important initial indication of the situations in which directional coronary atherectomy was most useful and helped set clear standards for performance of this procedure following FDA approval. PMID- 8213573 TI - Directional coronary atherectomy: how much lumen enlargement is optimal? AB - Until recently, it has not been clear how much of the effect of directional coronary atherectomy is due to tissue removal per se, and whether the long-term results of the procedure are helped or harmed when the operator attempts to obtain the "near zero percent" residual stenosis of which this technique is capable. This article summarizes the findings of a series of studies that have addressed these important questions and proposes a prescription for the optimal performance of directional atherectomy. Analysis of retrieved tissue weights compared with measured increases in luminal volume shows that about half of the improvement seen after directional atherectomy results from mechanical dilation. Because this "facilitated" dilation appears to take place within the bases of the trenches created by atherectomy cuts (rather than being randomly distributed in fractures throughout the plaque substance), a larger and smoother lumen is possible compared with that seen after conventional balloon dilation. Although the recovery of deep vessel wall components (media and even adventitia) is common, it generally does not cause either acute complications (i.e., perforation) or increase the probability of subsequent restenosis. Rather, reduction in the probability of late restenosis appears to be most directly related to the ability of directional atherectomy to provide the largest acute luminal diameter safely possible, thus providing better tolerance of subsequent intimal hyperplasia before hemodynamically significant renarrowing results at the treatment site. PMID- 8213574 TI - Balloon postdilation can safely improve the results of successful (but suboptimal) directional coronary atherectomy. AB - This study investigates whether adjunctive balloon angioplasty can be safely used to improve acute results in cases where directional coronary atherectomy alone has provided a successful (but suboptimal) outcome. Between October 1, 1990, and October 1, 1992, directional coronary atherectomy was performed successfully in 198 of 228 lesions. Individual operators believed that most acute results were satisfactory after atherectomy alone (group I, n = 115) with a minimal lumen diameter that increased from 0.82 +/- 0.45 to 3.21 +/- 0.65 mm after atherectomy, for an acute gain in lumen diameter of 2.39 +/- 0.73 mm and a residual stenosis of 6 +/- 13%. In 42% of lesions (group II, n = 83), however, results were considered suboptimal after atherectomy alone, with a minimal lumen diameter that increased from 0.85 +/- 0.45 to 2.83 +/- 0.64 mm, a smaller acute gain of 1.96 +/ 0.72 mm, and a mean residual stenosis of 17 +/- 14% (although all residual stenoses were < 50%, 19% had a residual stenosis > 30%). Adjunctive balloon angioplasty in these group II lesions provided an additional gain of 0.34 +/- 0.38 mm, bringing the total acute gain for group II lesions to 2.32 +/- 0.78 mm and the residual stenosis to 9 +/- 13%, similar to that of group I patients who underwent atherectomy alone. This strategy resulted in a 7 +/- 13% overall residual stenosis for the study population, with no higher incidence of periprocedural complications or adverse late clinical outcomes in group II patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213575 TI - Histologic analysis of directional coronary atherectomy samples. A review of findings and their clinical relevance. AB - Histologic analysis of atherectomy samples from > 400 patients who received directional coronary atherectomy at 3 separate institutions disclosed 2 major categories of tissue: atherosclerotic plaque (with or without thrombus) and intimal proliferation (hyperplasia, with or without thrombus). The predominant tissue type in atherectomy samples from native, primary, or de novo coronary artery stenoses was atherosclerotic plaque. The predominant tissue type in atherectomy samples from restenosis lesions (prior balloon angioplasty, atherectomy, or both) was intimal proliferation with variable amounts of atherosclerotic plaques (with or without thrombus). Deep vessel wall components (media, adventitia) were identified at varying frequencies. The clinical relevance of atherectomy tissue is reviewed. PMID- 8213576 TI - Molecular biology: insight into the causes and prevention of restenosis after arterial intervention. AB - Very little is known about the development of postatherectomy or postangioplasty restenosis. Morphologically, restenosis lesions are primarily composed of smooth muscle cells with associated matrix proteins and develop within 3-6 months. Although some degree of smooth muscle cell proliferation is a necessary part of the healing process after injury, it is unclear why only some individuals develop clinically significant lesions. Platelet deposition and release of growth factors have been postulated to be important in initiating the cellular growth response after vascular injury. Current data suggest that growth factors synthesized locally in the vessel wall may be very important in controlling smooth muscle proliferation. In addition, atherosclerotic plaques contain many procoagulant proteins that are exposed by angioplasty or atherectomy. These proteins stimulate a coagulation response and the activation of thrombin, resulting in platelet aggregation and thrombus formation. Thrombin mediates several biologic responses that may facilitate vascular lesion formation and can act directly as a smooth muscle mitogen. Vascular lesion formation as a result of percutaneous transluminal coronary angioplasty or atherectomy may be stimulated by a combination of factors, including platelet deposition and thrombin action, ultimately generating an autocrine growth response in the vessel wall. PMID- 8213577 TI - Analysis of atherectomy specimens. AB - Atherectomy specimens may be regarded as biopsy tissue excised from human vascular target lesions. Proceeding from contrary histologic findings that attribute focal hypercellularity to restenosis, and hypocellularity to chronic lesions, further analysis of atherectomy specimens was performed to study ultrastructural characteristics and functional aspects propagated by both lesion types. Transmission electron microscopy examination showed that intimal smooth muscle cells (SMCs) were the predominant cells in both primary and restenotic lesions. SMCs exhibited variable degrees of metabolic activation, typically higher in SMCs of restenotic lesions. This SMC phenotype was equally expressed when tissue samples were placed in a cell culture model. In an attempt to quantify SMC activity, proliferative as well as migratory activities of cultured cells were measured by growth curves and a computer-assisted motion analysis system, respectively. A 2- to 3-fold increase of both activity determinants was observed with SMCs cultivated from restenotic lesions compared with those from primary lesions, irrespective of their coronary or peripheral origin. Drug induced interference of human SMC metabolic activation and antagonism to their proliferative and migratory activities may be helpful in evaluation of therapeutic concepts to prevent restenosis. The antitubulin colchicine was studied for its effect on the defined determinants. The data in vitro demonstrate that colchicine decreased proliferative and migratory activity of SMCs and caused disorganization of the cytoplasmic ultrastructure. In conclusion, electron microscopy and cell culture studies may help to shed more light on the structures and mechanisms underlying restenosis and plaque growth. Deliberate counteraction of any of the specific early events implicated in these complex pathobiologic processes may eventually become effective means to suppress restenosis and may thus result in a prophylactic as well as therapeutic treatment of the diseased vascular wall. PMID- 8213578 TI - Attenuation of left ventricular dilatation after acute myocardial infarction by early initiation of enalapril therapy. CONSENSUS II Multi-Echo Study Group. AB - This trial investigated the effect of enalapril, administered early, on left ventricular (LV) volumes after myocardial infarction. Four hundred twenty-eight patients included in the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS II) were examined with echocardiography within 5 days, at 1 month and at 6 months after myocardial infarction. Enalaprilat (1 mg) or placebo infusion was initiated within 24 hours after infarction, followed by oral treatment to a target dose of 20 mg/day. A significant attenuation of LV dilatation was noted at 1 month in patients treated with enalapril compared with those receiving placebo. Changes in LV end-diastolic volume indexes during the first month were (mean +/- SEM) 5.7 +/- 1.0 ml/m2 for the placebo group and 1.9 +/- 0.8 ml/m2 for the enalapril group (p < 0.02). Changes in LV end-systolic volume indexes were 3.1 +/ 0.8 and 0.5 +/- 0.6 ml/m2, respectively (p < 0.02). The between-group difference was most marked in patients with anterior wall infarction (p < 0.005). Volume changes beyond the first month were similar in both groups but the differences observed at 1 month were maintained. The larger volumes in the placebo versus enalapril group were significant or borderline significant at 1 and 6 months. Thus, enalapril treatment initiated early after myocardial infarction and continued for 6 months can attenuate LV dilatation during the first month resulting in smaller LV volumes after 1 and 6 months. PMID- 8213579 TI - A difference between front-loaded streptokinase and standard-dose recombinant tissue-type plasminogen activator in preserving left ventricular function after acute myocardial infarction (the Central Illinois Thrombolytic Therapy Study). AB - A blinded, randomized trial compared the effects of front-loaded streptokinase with those of the conventional dose of intravenous recombinant tissue-type plasminogen activator (rt-PA) on left ventricular (LV) function after acute myocardial infarction (AMI). Thrombolytic therapy was administered in the emergency departments of 30 community hospitals in central Illinois, and subsequent studies were performed at 1 tertiary referral center. Patients aged < or = 75 years with a first AMI who could be treated within 4 hours of the onset of chest pain were randomly assigned to receive either streptokinase (375,000 IU bolus, followed by 1,125,000 IU over 1 hour) or rt-PA (10 mg bolus, followed by 50 mg in the first hour, and 20 mg/hour for the next 2 hours). All patients were treated with aspirin (325 mg) and intravenous heparin. Patients were transferred for angiography within 24 hours. During the 30-month study, 253 patients were treated with intravenous thrombolytic therapy 2.4 +/- 1.0 hour after the onset of AMI. In patients with anterior wall AMI (n = 90), global LV ejection fraction measured by angiography within 24 hours was 45 +/- 12% with rt-PA, and 39 +/- 13% with streptokinase (p < 0.03). Convalescent radionuclide angiography documented a persistent beneficial effect of rt-PA on LV regional wall contractility, but not global ejection fraction. There were no differences between rt-PA and streptokinase in preserving global or regional LV function in patients with inferior wall AMI. PMID- 8213580 TI - Comparison of myocardial perfusion imaging with technetium-99m tetrofosmin versus thallium-201 in coronary artery disease. AB - Technetium-99m (Tc-99m) tetrofosmin, a new myocardial perfusion imaging agent, was evaluated at exercise and rest in 50 patients with documented coronary artery disease to determine myocardial kinetics, redistribution and ideal imaging time. Planar imaging was performed at 5, 30, 60, 90, 120 and 240 minutes after an injection of Tc-99m tetrofosmin (8 to 10 mCi) at peak graded ergometric exercise. Reinjection (24 to 30 mCi) was performed at rest, 4 hours after the stress injection and also on a separate day, and imaging was repeated. All patients underwent thallium-201 (Tl-201) exercise and redistribution (4-hour) imaging. Perfusion defect to normal, and heart to lung ratios were calculated for exercise Tc-99m tetrofosmin images at each time point. The mean +/- SD defect to normal ratios were 0.75 +/- 0.10, 0.75 +/- 0.10, 0.74 +/- 0.09, 0.73 +/- 0.10, 0.73 +/- 0.10 and 0.72 +/- 0.10 at 5, 30, 60, 90, 120 and 240 minutes, respectively (p = NS), suggesting absence of redistribution. There was a significant increase in lung uptake of Tl-201 during exercise (p < 0.05), but not with Tc-99m tetrofosmin (p = NS). Washout of Tc-99m tetrofosmin was calculated in a subset of patients (n = 23). Rapid background clearance enabled postexercise diagnostic imaging as early as 5 minutes after injection. Myocardial retention curves after rest injection suggested that the optimal time for imaging was approximately 30 minutes later. Slow myocardial washout (4%/hour after exercise and 0.6%/hour after rest injection) enabled diagnostic images to be obtained up to 4 hours after each study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213581 TI - Clinical and angiographic predictors of immediate recoil after successful coronary angioplasty and relation to late restenosis. AB - The effect of immediate recoil on the results of balloon angioplasty was examined in a group of 416 patients (596 lesions) who underwent successful coronary angioplasty. Immediate recoil was responsible for loss of 0.42 +/- 0.64 mm from the potentially achievable lesion diameter, and represented 23% of the actual gain in diameter. The immediate recoil was determined mainly by the degree of arterial stretch, which is best represented by the balloon to normal artery size ratio (correlation coefficient 0.49, p < 0.0001). Classic risk factors for coronary artery disease did not affect immediate recoil, except for a trend toward lower values in patients with history of hypercholesterolemia. There was a tendency for lower recoil in patients with residual coronary thrombus and in those who underwent angioplasty within 1 week of acute myocardial infarction. Recoil was larger in the left anterior descending artery than in the circumflex or the right coronary artery. Patients with more immediate recoil developed more restenosis (> 50% stenosis at follow-up). However the late loss of luminal diameter due to the restenotic process was smaller in those who had larger initial recoil. It is concluded that immediate recoil after balloon angioplasty is an elastic phenomenon that is related mainly to the degree of arterial stretch. The relative importance of immediate recoil in determining the late outcome of coronary angioplasty is at least as important as the late restenotic process. PMID- 8213582 TI - Responses of heart rate variability to coronary occlusion during coronary angioplasty. AB - Signs of sympathetic activation are frequent during the early hours of anterior wall acute myocardial infarction, whereas parasympathetic reflexes predominate in inferior wall acute myocardial infarction. To assess the immediate autonomic responses to acute coronary occlusion, the high-frequency power and root-mean square successive difference, frequency and time domain measures of heart rate (HR) variability were analyzed in 73 cases of significant (50 to 95%) coronary artery stenosis immediately before and during balloon occlusion (mean 99 seconds). The range of nonspecific changes was formed on the basis of a control group with no ischemia during dilatations of 16 totally occluded coronary arteries. Balloon occlusion of the left anterior descending artery (n = 35) caused an abnormal increase in the measures of HR variability as a sign of vagal activation in 8 patients (23%), and a significant decrease in HR variability in 4 (11%). Occlusion of the left circumflex artery (n = 19) caused an increase in HR variability in 5 patients (26%), and a decrease in 2 (11%). Right coronary artery occlusion (n = 19) caused an increase in HR variability in 5 patients (26%) and a decrease in 4 (21%). Thus, coronary occlusion causes immediate changes in HR variability in greater than one third of patients with coronary artery disease. The direction of these initial HR variability changes cannot be predicted by the site of coronary occlusion. PMID- 8213583 TI - Effects of pravastatin in patients with serum total cholesterol levels from 5.2 to 7.8 mmol/liter (200 to 300 mg/dl) plus two additional atherosclerotic risk factors. The Pravastatin Multinational Study Group for Cardiac Risk Patients. AB - This placebo-controlled, multinational study evaluated the use of pravastatin in 1,062 patients with hypercholesterolemia (serum total cholesterol concentrations of 5.2 to 7.8 mmol/liter [200 to 300 mg/dl]) and > or = 2 additional risk factors for atherosclerotic coronary artery disease. Efficacy and safety analyses were performed on the initial 26-week, randomized, double-blind, placebo-controlled period; further safety analyses were conducted on the subsequent 52 weeks, which included an additional 26-week double-blind phase permitting other lipid-lowering agents and a final 26-week open-label period. At offweeks, pravastatin at a dose of 20 mg once daily at bedtime significantly lowered serum low-density lipoprotein cholesterol 26% (4.7 to 3.5 mmol/liter [182 to 135 mg/dl]), total cholesterol 19% (6.8 to 5.6 mmol/liter [263 to 217 mg/dl]) and triglycerides 12% (1.8 to 1.6 mmol/liter [159 to 142 mg/dl]) (p < 0.001 compared with placebo) and significantly raised serum high-density lipoprotein cholesterol 7% (1.1 to 1.2 mmol/liter [43 to 46 mg/dl]) (p < 0.001 compared with placebo). Efficacy of pravastatin was maintained at 26 weeks, and during this initial period there were significantly more serious cardiovascular adverse events in the placebo group (13 events, 2.4%) than in the pravastatin group (1 event, 0.2%) (p < 0.001). Six myocardial infarctions, 5 cases of unstable angina and 1 sudden cardiac death occurred in the placebo group, compared with none of these events in the pravastatin group. In this study, pravastatin produced beneficial effects on serum lipids and was associated with a reduction in the incidence of serious cardiovascular adverse events. PMID- 8213584 TI - Slowing of mitral valve annular calcium in systemic hypertension by nifedipine and comparisons with enalapril and atenolol. AB - Mitral annular calcium (MAC) is a condition that often occurs in patients with systemic hypertension. To evaluate the effectiveness of nifedipine in preventing MAC, 223 patients with systemic hypertension of recent onset and without MAC were selected and randomly enrolled in 3 groups: group 1 (76 patients) received nifedipine; group 2 (72 patients) received enalapril; and group 3 (75 patients) received atenolol. After 5 years, these treatments significantly reduced systolic (p < 0.001) and diastolic (p < 0.05) blood pressure (BP) in 3 treated groups. M mode echocardiography revealed MAC only in 2 patients in the nifedipine group (2.6%), in 13 in the enalapril group (18%) and in 15 in the atenolol group (20%). The degree of MAC was mild (< 5 mm) in the 2 patients in group 1, in 5 of the 13 in group 2, and in 6 of the 15 in the group 3, whereas it was severe (> 5 mm) in the remaining 8 in the enalapril group and in the other 9 in the atenolol group. There was also a significant correlation in the degree of MAC, left atrial enlargement and mitral regurgitation. In addition, atrial fibrillation and atrioventricular conduction defects were associated with severe MAC. These results indicate that nifedipine is an effective drug both in the long-term management of systemic hypertension and in preventing or delaying MAC. PMID- 8213585 TI - Risk of aortic dissection after aortic valve replacement. AB - Little information is available regarding the incidence of aortic dissection after previous aortic valve replacement (AVR), and factors associated with its development. Therefore, a meta-analysis of the literature was performed, and a patient population was studied retrospectively. Data from published studies showed that 87% of 31 patients were men (mean age 60 years), and 68% were known to have systemic hypertension. A dilated ascending aorta was observed at the time of AVR in 88% of patients. AVR was performed because of pure aortic regurgitation in 55% of patients, and combined aortic stenosis and regurgitation in 23%. More than 50% of patients did not survive dissection. The present series consisted of 7 patients. Four patients were known to the department before dissection occurred, and the other 3 were referred by other hospitals. Eighteen of 330 patients with previous AVR whose data were stored in an echocardiographic data base had an ascending aortic diameter > 50 mm. Of these 18 patients, aortic dissection occurred in 4. Three of the remaining 14 patients underwent elective ascending aortic replacement. Characteristics including sex, age, severity of dilatation, presence of progression in diameter, left ventricular function and time interval after AVR were not helpful in determining a cumulative risk for developing dissection. Because dissection occurred in 4 of 18 patients (22%) with an ascending aorta diameter > 50 mm, it is suggested to consider replacement of the ascending aorta during AVR when a value of 50 mm is exceeded. PMID- 8213587 TI - Disorders of the heartbeat: a historical overview from antiquity to the mid-20th century. PMID- 8213586 TI - Absence of left ventricular wall thickening in athletes engaged in intense power training. AB - There is a widely held perception that power training increases left ventricular (LV) wall thickness. Consequently, in individual power-trained athletes, confusion may legitimately occur with regard to the differential diagnosis of athlete's heart and nonobstructive hypertrophic cardiomyopathy. To investigate the effects of systematic strength training on cardiac dimensions (particularly absolute LV wall thickness), 100 relatively young and highly conditioned athletes participating in weight and power lifting, wrestling, bobsledding and weight throwing events for 3 to 24 years (mean 7) were studied by echocardiography. No athlete showed a maximal absolute LV wall thickness that exceeded the generally accepted upper limits of normal (i.e., 12 mm; range 8 to 12). When compared with 26 normal, sedentary control subjects of similar age and body surface area, maximal septal thickness was mildly but significantly greater in athletes (9.6 +/ 0.8 vs 9.0 +/- 0.5 mm; p < 0.001), as was the calculated LV mass index (96 +/- 12 vs 81 +/- 8 g/m2; p < 0.001); LV end-diastolic cavity dimension was similar in athletes and controls (55 +/- 4 and 54 +/- 3, respectively; p > 0.05). Consequently, echocardiographic data in this selected group of purely strength trained athletes show that whereas this form of conditioning is associated with increased LV mass and a disproportionate increase in wall thickness in relation to cavity dimension, only modest alterations in absolute wall thickness occur (which do not exceed upper normal limits). Therefore, in highly conditioned, strength-trained, competitive athletes, the presence of substantial LV wall thickening (> 13 mm) should suggest alternative explanations, such as the diagnosis of pathologic hypertrophy (i.e., hypertrophic cardiomyopathy). PMID- 8213588 TI - Cholesterol and atherosclerosis: "the new is the old rediscovered". PMID- 8213589 TI - The rapid reduction in cardiac events with lipid-lowering therapy: mechanisms and implications. PMID- 8213590 TI - On the mechanism of functional mitral regurgitation. PMID- 8213591 TI - Preserved walking-induced cardioacceleration in the elderly despite reduced heart rate response to standing. PMID- 8213592 TI - Renal, hemodynamic and neurohormonal effects of atrial natriuretic factor in cardiac allograft recipients treated with cyclosporin A. PMID- 8213593 TI - Left ventricular mass determined by transesophageal echocardiography and correlation with transthoracic echocardiography. PMID- 8213594 TI - Three-dimensional reconstruction of the descending thoracic aorta from transesophageal echocardiographic images. PMID- 8213595 TI - Pulmonary venous flow patterns assessed by transesophageal pulsed Doppler echocardiography in left atrial myxoma. PMID- 8213596 TI - Closure of hemodynamically insignificant ventricular septal defect after infective endocarditis. PMID- 8213597 TI - Two-dimensional echocardiographic and color Doppler measurements of atrial septal defect, and comparison with the balloon-stretched diameter. PMID- 8213598 TI - Assessment of left ventricular wall motion in angina pectoris by two-dimensional echocardiography and myocardial perfusion by technetium-99m sestamibi tomography during adenosine-induced coronary vasodilation and comparison with coronary angiography. AB - Myocardial perfusion and regional wall motion during adenosine-induced coronary vasodilation were assessed in 40 patients with angina pectoris by technetium-99m sestamibi single-photon emission computed tomography (SPECT) and simultaneous 2 dimensional echocardiography. Adenosine was infused intravenously at a dose of 140 micrograms/kg body weight per minute for 6 minutes, and technetium-99m sestamibi was injected at 3 minutes. Adenosine caused a significant decrease in systolic and diastolic blood pressure and a significant increase in heart rate and the heart rate-blood pressure product. Adverse effects were mild and transient and no patient required aminophylline. Completely or partially reversible defects on SPECT were present in 28 patients, a fixed defect was seen in 4 patients, and no defect was seen in 8 patients. Two-dimensional echocardiography revealed a new or worsening wall motion abnormality in 21 patients, a fixed abnormality in 4 patients and no abnormality in 15. Transient perfusion defects were associated with transient wall motion abnormalities in 71% of cases. The overall sensitivity, specificity and predictive accuracy of adenosine echocardiography in detecting significant coronary artery disease (> 50% diameter stenosis) were 74, 100 and 78%, respectively, whereas those of adenosine SPECT were 94, 100 and 95%, respectively (p < 0.05, NS, and < 0.05, respectively). Thus adenosine technetium-99m sestamibi SPECT has a higher sensitivity and predictive accuracy than adenosine echocardiography, suggesting that adenosine-induced perfusion defects are not always associated with wall motion abnormality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213599 TI - Regional myocardial blood flow in stable angina pectoris associated with isolated significant narrowing of either the left anterior descending or left circumflex coronary artery. AB - Myocardial perfusion measurements were obtained with positron emission tomography under basal conditions and after intravenous dipyridamole infusion (0.56 mg/kg over 4 minutes) to determine if myocardial perfusion is maximized in areas of resting wall motion abnormalities in patients with stable angina. Thirty-three patients with no history of myocardial infarction, and with coronary stenosis > 50% involving the left anterior descending (n = 24) and left circumflex (n = 9) coronary arteries were evaluated. Quantitative perfusion images were recorded twice in each subject using nitrogen-13 ammonia at baseline and after intravenous administration of dipyridamole. Computer-assisted analysis of left ventriculograms showed abnormal wall motion in the stenosis-related regions in 16 patients (group 1), and normal regional function in 17 (group 2). The flow values in the anterior and posterolateral wall were considered to reflect left anterior and left circumflex coronary artery flow, respectively. Quantitative angiography showed that coronary stenosis severity was higher in group 1 than in group 2 (cross-sectional area reduction 94 +/- 7% vs 87 +/- 11%; p < 0.05). Resting blood flow in the stenosis-related areas was significantly lower than in contralateral regions in group 1 (0.66 +/- 0.19 vs 0.77 +/- 0.26 ml/min/g; p < 0.05), but not in group 2 (0.73 +/- 0.18 vs 0.78 +/- 0.21 ml/min/g; p = NS). Dipyridamole significantly (p < 0.01) increased myocardial blood flow in both stenotic and remote regions in both groups 1 (0.95 +/- 0.41 vs 1.57 +/- 0.70 ml/min/g) and 2 (1.54 +/- 0.53 vs 2.01 +/- 0.84 ml/min/g).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213600 TI - Improvement in exercise tolerance and immediate beta-adrenergic blockade with intranasal propranolol in patients with angina pectoris. AB - A new intranasal spray formulation of propranolol was developed to provide beta adrenergic blocking medication on an immediate basis to patients with angina pectoris. The effects of this spray or placebo were assessed in 16 patients with effort-induced angina in a blinded, randomized, cross-over design study that compared placebo with intranasal propranolol spray (5 mg/puff) 15 minutes before exercise on a treadmill (Bruce protocol). One week later, each patient, acting as his/her own control, received the alternative treatment and repeated exercise. Mean plasma propranolol level with active therapy was 20 ng/ml. Patients with active spray demonstrated a significant increase in total exercise time than patients taking placebo (530 +/- 197 vs 460 +/- 177 seconds, p = 0.05), an increase in the time to 1 mm ST-segment depression on the electrocardiogram (384 +/- 202 vs 327 +/- 144 seconds, p < 0.05), and an increase in time to onset of angina (452 +/- 149 vs 363 +/- 175 seconds, p = 0.0005). There was a blunting of maximal exercise heart rate with active therapy compared with placebo (120 +/- 13 vs 133 +/- 17 beats/min, p < 0.01), blunting of maximal exercise systolic blood pressure (185 +/- 22 vs 194 +/- 21 mm Hg, p < 0.05), and blunting of peak double product (p < 0.0005), with more modest effects on resting heart rate. Propranolol spray is an effective approach for providing immediate beta blockade and improving exercise tolerance in patients with angina pectoris. PMID- 8213601 TI - Value of the electrocardiogram in diagnosing the number of severely narrowed coronary arteries in rest angina pectoris. AB - The aim of this study was to assess the value of the electrocardiogram recorded during chest pain for identifying high-risk patients with 3-vessel or left main stem coronary artery disease (CAD). Therefore, the number of leads with abnormal ST segments, the amount of ST-segment deviation, and specific combinations of leads with abnormal ST segments were correlated with the number of coronary arteries with proximal narrowing of > 70%. Electrocardiograms recorded during chest pain were compared with one from a symptom-free episode. In this retrospective analysis, 113 consecutive patients were included. One-vessel CAD was present in 47 patients, 2-vessel CAD in 22, 3-vessel CAD in 24 and left main CAD in 20. Stratification was performed according to the presence of an old myocardial infarction. The number of leads with ST-segment deviations, and the amount of ST-segment deviation in the electrocardiogram obtained during chest pain at rest showed a positive correlation with the number of diseased coronary arteries. These findings were more marked when the absolute shifts from baseline were considered, because ST-segment abnormalities could be present also in the electrocardiogram obtained during the symptom-free episode. Left main and 3 vessel CAD showed a frequent combination of leads with abnormal ST segments: ST segment depression in leads I, II and V4-V6, and ST-segment elevation in lead aVR. The negative predictive and positive accuracy of this pattern were 78 and 62%, respectively. When the total amount of ST-segment changes was > 12 mm, the positive predictive accuracy for 3-vessel or left main stem CAD increased to 86%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213602 TI - Health effects of dietary fructose. PMID- 8213603 TI - Manufacturing, composition, and applications of fructose. AB - High-fructose syrups (HFS) comprise fructose, dextrose, and minor amounts of oligosaccharides. The predominant syrups of commerce contain 42% and 55% fructose. HFS production was made possible by concurrent developments in refining, isomerization, and separation technologies in the 1960s. Fructose contributes many useful physical and functional attributes to food and beverage applications, including sweetness, flavor enhancement, humectancy, color and flavor development, freezing-point depression, and osmotic stability. HFS is used extensively in carbonated beverages, baked goods, canned fruits, jams and jellies, and dairy products. The use of crystalline fructose and crystalline fructose syrup have recently expanded from pharmaceutical and specialty food products to mainstream food and beverage applications. PMID- 8213604 TI - Worldwide production of high-fructose syrup and crystalline fructose. AB - High-fructose syrups (HFS) are now manufactured and used in many countries throughout the world. They are produced from a variety of starch raw materials including corn, rice, tapioca, wheat, cassava, and sugar beet pulp. Production of HFS is highly dependent on local sucrose and economics of agricultural raw materials. HFS is produced and consumed in the largest quantity in the United States by using corn starch as the raw material. Eastern Europe, the former Soviet Union, and Asia are major growth areas for HFS production. Crystalline fructose is now being used in a growing number of food applications but its production represents a small percentage of total fructose sweeteners. PMID- 8213605 TI - Intakes and food sources of fructose in the United States. AB - Examination of the per capita disappearance data for sweeteners and other sources of fructose showed that during the past two decades there was a considerable increase in the availability of free fructose in the food supply. However, the availability of the total amount of fructose, which includes both free and bound fructose, has remained relatively constant. Estimates of the average daily intake of fructose, based on the 1977-78 USDA Nationwide Food Consumption Survey, ranged from 15 g for infants to 54 g for males aged 15-18 y with a mean of 37 g for the total population. These values represent 7-9% of the energy intake (8% for the total population). For most sex/age groups nonalcoholic beverages (eg, soft drinks and fruit-flavored drinks) and grain products (eg, sweet bakery products) were the major sources of fructose; fruits and fruit products were the major sources of naturally occurring fructose; nonalcoholic beverages were the major sources of added fructose. PMID- 8213606 TI - Fructose absorption. AB - Fructose found in modern diets as a constituent of the disaccharide sucrose is absorbed by a well-characterized absorptive system integrating enzymatic hydrolysis of the disaccharide and transfer of the resulting two monosaccharides through the apical membrane of the epithelial cell. The increasing use of high fructose syrups and crystalline fructose prompted new studies aimed at the determination of the absorptive capacity for free fructose in the human gut. Results indicate that the capacity for fructose absorption is small compared with that for sucrose and glucose and is much less than previously estimated. The unexpected finding that the simultaneous ingestion of glucose can prevent fructose malabsorption suggests that the pair of monosaccharides might be absorbed by the disaccharidase-related transport system as if they were the product of the enzymatic hydrolysis of sucrose. This absorptive mechanism might not be able to transport fructose when ingested without glucose. PMID- 8213607 TI - Intermediary metabolism of fructose. AB - Most of the metabolic effects of fructose are due to its rapid utilization by the liver and it by-passing the phosphofructokinase regulatory step in glycolysis, leading to far reaching consequences to carbohydrate and lipid metabolism. These consequences include immediate hepatic increases in pyruvate and lactate production, activation of pyruvate dehydrogenase, and a shift in balance from oxidation to esterification of nonesterified fatty acids, resulting in increased secretion of very-low-density-lipoprotein (VLDL). These effects are augmented by long-term absorption of fructose, which causes enzyme adaptations that increase lipogenesis and VLDL secretion, leading to triglyceridemia, decreased glucose tolerance, and hyperinsulinemia. Acute loading of the liver with fructose causes sequestration of inorganic phosphate in fructose-1-phosphate and diminished ATP synthesis. Consequently, the inhibition by ATP of the enzymes of adenine nucleotide degradation is removed and uric acid formation accelerates with consequent hyperuricemia. These effects are of particular significance to potentially hypertriglyceridemic or hyperuricemic individuals. PMID- 8213609 TI - Fructose and mineral metabolism. AB - Fructose affects to some extent the bioavailability of iron, zinc, and copper. Its effect on copper has been studied most intensively. Fructose forms stable complexes with iron and promotes its absorption and also that of zinc. Compared with starch, fructose and sucrose decrease copper bioavailability in rats fed diets based on egg white and containing 60% carbohydrate. There is no apparent fructose effect on copper bioavailability in pigs. In humans fructose consumed as 20% of energy has no effect on copper balance and minimal effects on the criteria of copper status. PMID- 8213608 TI - Fructose and dietary thermogenesis. AB - Ingestion of nutrients increases energy expenditure above basal metabolic rate. Thermogenesis of carbohydrate comprises two distinct components: an obligatory component, which corresponds to the energy cost of carbohydrate absorption, processing, and storage; and a facultative component, which appears to be related with a carbohydrate-induced stimulation of the sympathetic nervous system, and can be inhibited by beta-adrenergic antagonists. Fructose ingestion induces a greater thermogenesis than does glucose. This can be explained by the hydrolysis of 3.5-4.5 mol ATP/mol fructose stored as glycogen, vs 2.5 mol ATP/mol glucose stored. Therefore the large thermogenesis of fructose corresponds essentially to an increase in obligatory thermogenesis. Obese individuals and obese patients with non-insulin-dependent diabetes mellitus commonly have a decrease in glucose induced thermogenesis. These individuals in contrast display a normal thermogenesis after ingestion of fructose. This may be explained by the fact that the initial hepatic fructose metabolism is independent of insulin. This observation indicates that insulin resistance is likely to play an important role in the decreased glucose-induced thermogenesis of these individuals. PMID- 8213610 TI - Protein fructosylation: fructose and the Maillard reaction. AB - Fructose, as is the case for other reducing sugars, undergoes the Maillard reaction with proteins and amino acids. The first stage of the reaction results in one or more substituted amino sugars. These products in turn enter the advanced and final stages of the Maillard reaction, which involve the formation of reactive intermediates, cross-linking of proteins, and the formation of brown and fluorescent polymeric materials. It would appear that the initial stages of the reaction occur more rapidly with fructose than with glucose. The Maillard reaction with any sugar, including fructose, results in a decrease in protein quality due to the loss of amino acid residues and decreased protein digestibility. Maillard products can inhibit the uptake and metabolism of free amino acids and of other nutrients such as zinc and some advanced Maillard products have mutagenic and/or anticarcinogenic properties. In vivo the Maillard reactions between proteins and fructose, glucose, and other reducing sugars may play a role in aging and in some of the clinical complications of diabetes. PMID- 8213611 TI - Inborn errors of fructose metabolism. AB - A review is presented of genetic defects affecting fructose metabolism in humans. Presently, six conditions have been recognized: fructose malabsorption, fructokinase deficiency, aldolase A and aldolase B deficiency, fructose-1,6 diphosphatase deficiency and D-glyceric aciduria. Clinical presentations of these conditions, enzymatic and/or molecular defects, pathophysiological consequences, and modes of treatments are discussed. PMID- 8213612 TI - Diabetes and fructose metabolism. AB - The clinical aspects of fructose supplementation in the diets of individuals with diabetes should focus on the balance between beneficial effects and possible side effects. Fructose supplementation in diabetes mellitus was advocated before insulin was discovered. Fructose elicits a lower glucose and insulin response in healthy individuals and in individuals with diabetes. The use of fructose as a sweetener in the diets of diabetics has been debated repeatedly. Short-term studies have now shown that substitution of fructose for sucrose in the diets of individuals with diabetes improves glycemic control and does not appear to have substantial side effects. In balanced diets, reasonable amounts of fructose supplementation do not affect lipoprotein metabolism or result in gastrointestinal symptoms. Long-term studies are still needed to ascertain that long-term fructose supplementation has a sustained beneficial effect in diabetes and is devoid of deleterious side effects. PMID- 8213613 TI - Dietary fructose effects on lipoprotein metabolism and risk for coronary artery disease. AB - In this chapter I have attempted to review the current literature drawing on those studies that I believe provide the best scientific evidence in regard to this issue. When those studies that provide the best scientific evidence are reviewed, there is evidence that increasing dietary fructose consumption can significantly increase fasting plasma triglyceride and cholesterol concentrations. Specifically, these changes are associated with an increase in both VLDL and LDL particles, without any apparent change in HDL particle concentrations. It appears that the magnitude of the deleterious effects vary depending on such factors as age; sex, baseline glucose, insulin, and triglyceride concentrations; the presence of insulin resistance; and the amount of dietary fructose consumed. Finally, not all studies are consistent in these findings, however, the positive data cannot easily be dismissed and may be of substantial clinical importance. This is particularly true given the fact that: 1) these deleterious changes occur in the absence of any beneficial effect on lipoprotein metabolism, and 2) these abnormalities in lipoprotein metabolism appear to be greater in those individuals already at an increased risk for coronary artery disease. PMID- 8213614 TI - Fructose and behavior: does fructose influence food intake and macronutrient selection? AB - Fructose, as compared with other sugars, may have a suppressant effect on subsequent food intake and may result in a different selection of macronutrients. The research investigating these effects and the possible underlying mechanisms of action is reviewed. These mechanisms include fructose's effects on the rate of gastric emptying, concentrations of plasma glucose and insulin, and hepatic metabolism. The research is not conclusive. Questions that remain to be examined more thoroughly are the time course of fructose's effects on food intake and macronutrient selection in the short-term, and effects of long-term administration of fructose on these appetitive processes. PMID- 8213615 TI - The influence of fructose feeding on physical performance. AB - Athletic competition requires great energy expenditure and the ability to maintain performance depends on an adequate supply of metabolic fuels, which has led to the use of dietary supplements. Much of the data concerning fructose supplementation is contradictory in nature, but it shows that fructose feeding before or during exercise can enhance performance under certain conditions. Preexercise nutrition seems to be the most important condition to be met. It has been theorized that prefeeding elevates liver glycogen and spares muscle glycogen, which prolongs activity. There is also good evidence to indicate that the addition of fructose to the diet during ultraendurance events can improve performance by 126%. The gastrointestinal discomfort created by large amounts of fructose can hinder performance and has limited research with this supplement. Therefore, even though positive effects have been demonstrated, more research is needed to determine the role that fructose can play in enhancing athletic performance. PMID- 8213616 TI - The public health significance of dietary fructose. AB - It is increasingly appreciated that some foods and food components, including fructose, have specific health benefits and/or potential risks. This recognition is associated with varied health claims and cautionary statements that can drive dynamic changes in food manufacture, selection, consumption, and views about food safety. It is imperative that the scientific and public health communities develop clear standards for evaluating potential benefits and risks, a process for accurately conveying sound public health information to consumers, and a mechanism for monitoring future changes in the food supply and relating these changes to potential health effects. In this paper we discuss specific and general considerations about the health effects of dietary fructose and provide a perspective on their public health significance. On the basis of currently available information, there is little basis for recommending increased or decreased use of fructose in the general food supply or in products for special dietary use. PMID- 8213617 TI - Issue in tribute to Jerome M. Vaeth, M.D. on the occasion of his retirement. PMID- 8213618 TI - Whole-lung irradiation for Kaposi's sarcoma. AB - Twenty-five patients were treated with whole-lung irradiation for symptomatic pulmonary KS. Treatment was most often given four days per week, 150 cGy per fraction, to 1050-1500 cGy (mean 1224 cGy). No acute toxicity was observed. 89% of patients completing therapy reported improvement in dyspnea. All patients responding symptomatically could reduce (and 78% could eliminate) oxygen use. Chest x-rays showed concurrent improvement in 78% of cases, although this was > or = 50% clearance of infiltrate in only 28%. Symptomatic improvement was prompt, always occurring during the 2-2 1/2 week therapy course. Clinical response was transient in some patients, but 12 weeks after therapy 56% remained symptomatically improved. Pulmonary KS indicated an advanced stage of AIDS and survival was short (mean: 15.7 weeks after completion of therapy). Patients with poor performance status (Karnovsky: < or = 30%) and progression of disease despite chemotherapy had very short survival (mean: 3.2 weeks). For such patients, a supportive care only approach without radiotherapy is suggested. For others, whole-lung irradiation provides prompt symptomatic improvement for most patients, and offers a simple treatment approach with little toxicity for often debilitated patients. PMID- 8213619 TI - Definitive external irradiation in stages A (T1) and B (T2) carcinoma of the prostate. AB - This is a retrospective review of records of 38 patients with clinical stage A (T1a,b), 131 with stage B1 (T2a), and 113 with B2 (T2b) histologically proven adenocarcinoma of the prostate treated with definitive irradiation. All patients have been followed for a minimum of 3 years (median follow-up: 6.5 years; maximum: 23 years). Patients were treated with high-energy photons (18-22 MV) with either 4,500 cGy to pelvic fields and a boost of about 2,000 cGy to the prostate or 6,600 cGy to the prostate and periprostatic tissues. Five patients with stage A1 (T1a) tumors had no failures. The local recurrence rate was 11% in stage T1b, 14% in T2a, and 17% in T2b tumors. Distant metastasis rates were 16% in patients with stage T1b, 20% in T2a, and 21% in T2b. The disease-free survival rate was approximately 70% at 5 years and 55% at 10 years in patients with stages T1b or T2, without significant differences among the various groups. The cause specific survival was 90% at 5 years and 70% at 10 years in the various groups. The results are comparable to those reported in several surgical or radiation therapy series at various institutions. A significantly lower disease-free survival was observed in patients with poorly differentiated tumors (40% at 5 years) in comparison with those with well- and moderately differentiated tumors (80% DFS at 5 years) (p < .001). Likewise, the cause-specific survival was lower in patients with poorly differentiated tumors (75% at 5 years) than in the other patients (91%) (p = .0003). No difference in the local recurrence rates with various degrees of differentiation was noted. However, patients with poorly differentiated tumors had a greater incidence of distant metastasis (30%-40%) than patients with well or moderately differentiated lesions (10%-20%). Performance of transurethral resection also was associated with a higher incidence of distant metastasis (40%) in patients with stage B2 (T2b) tumors than in those diagnosed by needle biopsy (20%) (p = .12) but not in the other groups. Age, race, volume irradiated, or doses of irradiation lower or higher than 6500 cGy did not significantly affect outcome. Radiation therapy is an effective treatment for patients with stage A (T1) or B (T2) carcinoma of the prostate. Careful selection and refinement of treatment techniques, including three dimensional treatment planning and conformal delivery irradiation or brachytherapy, may improve the management of these patients. PMID- 8213621 TI - Conservative treatment of retinoblastoma. The use of plaque brachytherapy. AB - Retinoblastoma is the most common intraocular malignancy in childhood. The tumor arises from multipotential retinal cells. Treatment options include enucleation, external beam radiotherapy, episcleral plaque radiotherapy, photocoagulation, cryotherapy or a combination of these modalities. In retinoblastoma 10% have a positive family history and of the remaining 90%, 35% represent germinal chromosomal mutations while 65% represent somatic chromosomal mutations. Therefore, approximately 40% of all retinoblastomas are hereditary and are transmitted as a highly penetrant autosomal dominant trait. In the Wills Eye/Hahnemann University experience an analysis of 400 consecutive patients, 103 tumors in 103 eyes were treated with solitary plaque radiotherapy. Tumor regression was observed in all patients initially. After 40 months mean follow up, persistent regression was observed in 89 cases (87%) and recurrences in 13 cases (13%). Of the 13 recurrences, five were in the group treated primarily (5/31) and eight in the group treated after failing other modalities (8/72). Plaque brachytherapy is an important tool in the management of retinoblastoma. Our preliminary data suggest that plaque brachytherapy is an effective treatment modality for primary treatment as well as after failure using other modalities. PMID- 8213620 TI - "Compensated" split-course versus continuous radiation therapy of carcinoma of the tonsillar fossa. Final results of a prospective randomized clinical trial of the Radiation Therapy Oncology Group. AB - The Radiation Therapy Oncology Group conducted a prospective comparison of a compensated split course radiotherapy technique (300 cGy x 10, 3 weeks rest, 300 cGy x 10), versus continuous radiotherapy (200-220 cGy up to 6000-6600 cGy), in 137 evaluable patients. The complete response (CR) was 57% in 63 patients, treated with the split-technique vs 61% in 74 patients submitted to continuous course radiotherapy. The completion of therapy as planned was better in the split technique, but acute and late tissue reactions were the same. Locoregional control of tumor at 5 years was 25% for split and 28% for continuous therapy. At 7 years this was 25% and 24%, respectively. Absolute survival in the split-course patients tended to be lower than in the continuous group, but when the sample of patients was enlarged by the addition of cases from similar trials of nasopharynx and base of tongue lesions, the survival difference was eliminated. On the basis of the results of this study we conclude that the stated compensated split-course technique gives equal clinical results as conventional continuous therapy, with the advantage of requiring fewer radiation fractions, and less burden on the patient and therapy facilities. PMID- 8213622 TI - An evaluation of the efficacy of postoperative irradiation in rectal adenocarcinoma. AB - Cancer of the colon and rectum is the second most common form of cancer in the United States. Although surgery is the primary treatment for rectal cancer, the overall 5-year survival approximates 50%. Pelvic failure rates and their associated morbidity have led to the use of postoperative irradiation, either alone or combined with chemotherapy. We reviewed 77 consecutive patients treated with postoperative irradiation to the pelvis following curative surgery. The prognosis is dependent on surgical stage and histologic grade. The minimal decrease in local recurrence in this study is offset by treatment-related small bowel injury. A subset of patients who may benefit from adjuvant treatment is yet to be defined. PMID- 8213623 TI - The in vitro radiosensitization of human glioblastoma with pentoxifylline. AB - There is evidence that pentoxifylline may be both a radioprotector of normal tissue and a radiosensitizer of tumor cells. This article reviews this evidence and then describes our own laboratory study to determine whether pentoxifylline is a radiosensitizer of human glioblastoma cells in vitro. Human glioblastoma multiforme cells (SNB19 cell line) were irradiated in vitro with and without pentoxifylline. Regression of the log ratios (quotient of surviving colonies) revealed greater tumor cell kill in the PTX group, and the difference increased as the radiation dose increased (p < 0.01 at the 750 and 1000 cGY doses). Before the hypothesis that PTX is a radiosensitizer of hypoxic tumor cells can be confirmed or denied, it must be determined if the agent also has a separate mechanism of tumoricidal activity. Whereas in vivo models allow the well documented rheologic, immunologic and oxygen-related effects of PTX to be active simultaneously, the in vitro model described herein excludes the effects of such systemic actions and focuses on mechanisms at the cellular or subcellular level. These data suggest there exists such a mechanism of tumoricidal activity of PTX that has not been previously identified. PMID- 8213624 TI - Interstitial iodine 125 and concomitant cisplatin followed by hyperfractionated external beam irradiation for malignant supratentorial glioma. Preliminary experience at the University of Tennessee, Memphis. AB - Between November 1989 and October 1992, 28 consecutive patients with glioblastoma multiforme (n = 18) or anaplastic astrocytoma (n = 10; includes one patient with oligodendroglioma with anaplastic astrocytoma component) were treated with interstitial iodine 125 (60 Gy over 6 days) and with concomitant cisplatin (via infusion on days 2-6 of the implant), then followed by hyperfractionated external beam irradiation (110 cGy delivered twice daily; 66 Gy planned total dose). Of 26 patients (60%) who received both 125I and HEBI, 15 are alive with no evidence of recurrent disease at a median follow-up of 18 months post-125I (range: 11 to 34 months). Four other disease-free patients succumbed to nontumor-related events. Two patients with local control had distant failure outside the HEBI treatment fields. Overall local control is 77%. Local failure occurred in 6 patients (23%) 2 to 11 months post-125I. Time to disease progression ranged from 4 to 18 months (median: 10 months). Survival (measured from the date of diagnosis) has ranged from 6 to 26 months (median: 15 months). All patients have maintained Karnofsky Performance Status within 20 points of their preimplant status, with the exception of a single patient who, following diagnosis of radiation necrosis and surgical intervention for symptomatic relief, had a 30-point drop in KPS. Radiation necrosis or persistent mass effect were noted by neuroimaging in seven patients, four of whom required surgical intervention following failed medical management. Ototoxicity, nephrotoxicity, peripheral nerve dysfunction, or hematologic toxicities have not been observed. This new innovative treatment approach offers a promising alternative to the normally dismal prognosis for patients with malignant gliomas. PMID- 8213625 TI - Intraoperative radiotherapy. A positive view. PMID- 8213626 TI - Nasopharyngeal brachytherapy. AB - There has been a recent resurgence of interest in implementing brachytherapy in the management of nasopharyngeal carcinoma, not only as treatment for recurrent disease, where it has secured a notable role, but also as an elective boost following external beam irradiation in an attempt to improve local control. Examination of the use of nasopharyngeal brachytherapy over nearly the last century may provide guidance for such endeavors and encourage further evolution of these techniques. Throughout this interval, ingenuity has prevailed in attempts to treat a secluded anatomical site which has been difficult to access, explore, and implant in an acceptable manner. PMID- 8213627 TI - Women's knowledge about breast cancer. Dimensions of knowledge and scale development. AB - Evidence suggests that knowledge about breast cancer may influence secondary prevention, care-seeking behavior, and participation in treatment decision making. Yet few standardized measures of breast cancer knowledge are in existence. Using factor analysis, this paper describes the structure of women's knowledge about breast cancer and uses that structure to develop a measurement scale. Principal axis factoring and varimax rotation yielded a nine factor solution, which accounted for 59.3% of the common variance. Interpretation of the conceptual structure of these factors suggests that knowledge is organized around breast cancer treatment, misconceptions, risk factors, symptoms, menstruation, and prevalence. Considering only those items with factor loadings of .35 and greater, and including only those factors containing three or more items, a 16 item scale, which included four factor-based subscales covering knowledge about breast cancer treatment, misconceptions, risks, and symptoms was developed. Internal consistency reliability of the total scale and of the four subscales was high (alphas = .76-.95). Using chi square analysis, it was found that levels of knowledge on the total scale and on the treatment and symptom subscales are associated with age, education, income, and history of breast cancer. Knowledge on the misconceptions subscale was associated with age, education, and income. Knowledge on the risks subscale was associated with age and education. Issues of reliability and validity of the scale as well as directions for future research in this area are discussed. PMID- 8213628 TI - Computer-aided documentation. Quality, productivity, coding, and enhanced reimbursement. AB - PURPOSE: Physicians currently use technology, where appropriate, to improve patient care, for example, MRI and three-dimensional radiotherapy dose planning. One area that has seen limited benefit from current technology is in documenting of medical information. DESIGN: Review of related literature and directed interviews. RESULTS: Technology is available to assist in documenting the initial patient encounter. Patient care, quality of practice, and reimbursement may be improved with careful implementation. CONCLUSION: It will be worthwhile for practices to examine how to implement this technology to obtain the potential benefits. PMID- 8213629 TI - The development of a small, economic mobile unit for intraoperative electron beam therapy. PMID- 8213630 TI - Progress in the classification of non-Hodgkin's lymphoma. PMID- 8213631 TI - Recommendations of the International Council for Standardization in Haematology for Ethylenediaminetetraacetic Acid Anticoagulation of Blood for Blood Cell Counting and Sizing. International Council for Standardization in Haematology: Expert Panel on Cytometry. AB - Of the three ethylenediaminetetraacetic acid (EDTA) salts used for anticoagulation of blood specimens for hematologic testing, potassium salts are the most readily soluble. Tripotassium EDTA is dispensed as a liquid and thus causes a slight dilution of the specimen. This salt also has been shown to affect the red blood cell size more at increased concentrations and on storage than the dipotassium salt. Therefore, dipotassium EDTA is recommended as the anticoagulant of choice in specimen collection for blood cell counting and sizing. The amount of dipotassium EDTA used is 1.5-2.2 mg (3.7-5.4 mumol) per milliliter of blood. PMID- 8213632 TI - Diffuse low-grade B-cell lymphomas. Four clinically distinct subtypes defined by a combination of morphologic and immunophenotypic features. AB - The authors studied 56 cases of diffuse low-grade B-cell lymphoma using frozen tissue sections and a large panel of monoclonal antibodies that distinguish subsets of normal B cells. They compared the immunophenotypes with the histologic subtypes defined by the Rappaport classification, Working Formulation, and Kiel classification to correlate antigen expression with the morphologic subtypes defined in these classification schemes and to define the contribution of immunophenotype to clinically relevant subclassification. All categories in all classifications showed some heterogeneity of antigen expression; however, antigen expression correlated better with four major subgroups defined by the Kiel classification: (1) CD5+ CD10- CD23+ CD43+: chronic lymphocytic leukemia (CLL); (2) CD5+ CD10-/+CD23- CD43+: centrocytic (mantle cell) lymphoma; (3) CD5- CD10+/- CD23-/+ CD43-: centroblastic/centrocytic (CB/CC) lymphoma; and (4) CD5- CD10- CD23-/+CD43-/+: immunocytoma, mucosa-associated lymphoid tissue (MALT)-type, and monocytoid B-cell lymphoma. These subgroups had distinctive clinical features. Patients with centrocytic lymphoma were predominantly male (5.5:1) and had a significantly worse probability of survival than those with either CLL or MALT type lymphoma (P = 0.001). The group with CB/CC lymphoma had an equal male-female ratio and an intermediate prognosis. Most patients with MALT-type and nodal monocytoid B-cell lymphomas were female (2:1); the disease-free survival for patients with extranodal MALT-type lymphoma was significantly better than that for all patients with other lymphoma subtypes except CB/CC (P < 0.01). The group with non-MALT immunocytoma had a slight male predominance, a high frequency of monoclonal gammopathy, and an intermediate prognosis. In differential diagnosis, CD23 was useful in distinguishing B-cell CLL from centrocytic lymphoma (P < 0.0001); CD5 (P < 0.0001), CD6 (P < 0.005), and CD43 (P < 0.0001) distinguish centrocytic lymphoma from CB/CC lymphoma; and CD10 (P < 0.005), CD43 (P = 0.06), Leu-8 (P = 0.08), and Ig heavy chain (P = 0.01) may help distinguish CB/CC lymphoma from immunocytoma, monocytoid B-cell lymphoma, and MALT-type lymphoma. Differences in antigen expression and clinical features among these Kiel classification subgroups suggest that they represent distinct biologic entities. The Working Formulation categories do not delineate these diseases clearly. PMID- 8213633 TI - Pattern of expression of CD45 RA/RO isoformic antigens in acute myeloblastic leukemia cells. AB - The authors used cell surface immunofluorescence to investigate the expression of CD45 RA (4KB5)/RO (UCHL1) antigen by acute myeloblastic leukemia (AML) cells from 78 patients. Four types--RA+/RO- (RO < 15%), RA-/RO+ (RA < 15%), mixed (20% RA and 20% RO), and RA-/RO- (RA < 10% and RO < 10%)--were observed. The number of cases with RA+/RO-, RA-/RO+, mixed, and RA-/RO- types in each French-American British subclass of AML were as follows: M1 (n = 22): 18, 4, 0, 0; M2 (n = 21): 16, 0, 5, 0; M3 (n = 14): 11, 0, 0, 3; M4: 2, 2, 1, 0; and M5: 5, 5, 6, 0, respectively. The M1 RA-/RO+ type, which was always CD7- CD34- HLA-DR-, constituted a rare and distinct M1 subtype because there was no mixed type among the M1 cases. All CD7+ AML cells were the RA+/RO- type and HLA-DR+ except one. The expression of CD45 RO antigen, found in patients with M2, M4, and M5 subtypes of AML, was thought to be associated with the maturity of blasts as monocyte or granulocyte lineage cells. CD45 antigen has tyrosine phosphatase activity in association with nonreceptor-type tyrosine kinases. It was speculated that the functional status and stage of differentiation of the granulocyte/monocyte lineage determine which type of nonreceptor-type tyrosine kinases will operate, which then select the pattern of expression of the CD45 isoform. Thus, the determination of tyrosine kinases associated with CD45 isoforms seems to be important in understanding the AML subsets defined by the pattern of CD45 RA/RO expression. PMID- 8213634 TI - Secondary (AA) amyloidosis associated with Castleman's disease. Report of two cases and review of the literature. AB - This article describes two patients with localized Castleman's disease (CD) of the mixed hyaline vascular and plasma cell type located at the mesentery of the small bowel, associated with systemic symptoms, anemia, an increased plasma level of acute phase reactants, and systemic amyloidosis. There were amyloid deposits on the vascular walls of the liver, spleen, and mesenteric lymphoid mass. On immunohistochemical studies, amyloid was shown to be of the AA type in both cases. After surgical resection of the mesenteric mass, clinical and laboratory manifestations improved, and the amyloidosis showed no progression in these patients 23 years and 1 year later. The authors' review of the literature shows a striking similarity of CD cases associated with amyloidosis in terms of the abdominal localization of the lymphoid mass, secondary pattern (AA type) of amyloidosis, and improvement of clinical manifestations after removal of the tumor, without progression of amyloid deposition. PMID- 8213635 TI - Rapid screening of Salmonella species from stool cultures. AB - The authors compared a three-minute fluorescence method (MUCAP test; Biolife Italiana, Milan, Italy) with standard microbiologic procedures for the presumptive identification of Salmonella from stool cultures on three solid culture media. From 976 suspect colonies, 176 proved to be Salmonella by the traditional methods. They all were detected by the MUCAP test (sensitivity, 100%). There were 65 false-positive results, corresponding mostly to Pseudomonas (specificity, 91.8%). Neither the culture medium used nor the production of H2S affected the accuracy of the test. The results from this study showed that the MUCAP test is a rapid, simple, and sensitive method for the presumptive identification of Salmonella species. PMID- 8213636 TI - Diagnosis of cytomegalovirus pneumonia by the polymerase chain reaction with archived frozen lung tissue and bronchoalveolar lavage fluid. AB - The authors developed a polymerase chain reaction (PCR) procedure to detect cytomegalovirus (CMV) in archived, frozen lung tissue and bronchoalveolar lavage (BAL) fluid preparations. The procedure incorporated an internal beta-globin control to assess the adequacy of the sample. Twenty-nine lung tissue and 96 archived BAL specimens from marrow transplant recipients were tested. One of the lung tissue specimens and 46 of the BAL specimens had insufficient tissue for PCR analysis because they did not show a beta-globin band. In lung tissue, the PCR had a sensitivity of 100% and specificity of 89% compared with conventional tube culture. In BAL specimens, the PCR had a sensitivity of 87% and specificity of 90% compared with conventional tube culture or centrifugation culture. Provided tissue was sufficient, the results suggest that the PCR can be used to diagnose CMV interstitial pneumonia effectively from frozen specimens of lung tissue or BAL fluid. PMID- 8213637 TI - Protein-osmolality ratio for the quantitative assessment of proteinuria from a random urinalysis sample. AB - Proteinuria evaluation is important for the differential diagnosis of renal disease and the assessment of prognosis and response to therapy. Qualitative proteinuria correlates poorly with quantitative 24-hour protein levels because of hydration and methodologic problems associated with observer error. The authors automated quantitative urinary protein and osmolality measurements and evaluated whether a urinary protein-osmolality ratio (mg/L/mOsm/kg) in the random urinalysis predicts the 24-hour urine protein level. They compared this ratio with the (1) 24-hour protein levels in 78 normal women and 53 normal men; (2) 24 hour protein levels in 129 proteinuric patients; and (3) urinary protein creatinine ratio in 131 normal patients and 105 proteinuric patients. The normal urinary protein-osmolality ratio was less than 0.12 (sensitivity, 96%; specificity, 93%). This compared to a urinary protein-creatinine ratio of less than 0.05 (sensitivity, 96%; specificity, 90%). A urinary protein-osmolality ratio of greater than 2.5 indicates a level of more than 3.0 g/24 hour (sensitivity, 91%; specificity, 98%). The urinary protein-osmolality ratio = 1.12x + 0.05 (r = 0.88), where x = 24-hour protein. The authors conclude that the quantitative urinary protein-osmolality ratio is better than a qualitative urinalysis and urinary protein-urinary creatinine ratio for detecting or assessing abnormal proteinuria and allows for a reasonable prediction of 24-hour protein levels. PMID- 8213638 TI - Subclinical human immunodeficiency virus-related changes in oral mucosa shown by image analysis of tongue smears. AB - There is evidence that certain lesions of the oral mucosa, such as hairy leukoplakia (HL), in patients seropositive for human immunodeficiency virus correlate with the subsequent development of acquired immune deficiency syndrome. The authors suggest that HL is a final manifestation of alterations that gradually develop after HIV infection. To recognize inapparent early subclinical changes in oral mucosa, the authors applied methods of digital image analysis to investigate tongue smears from healthy control subjects and immunosuppressed patients after chemotherapy and HIV infection. Their studies concentrated on nuclear morphologic features and chromatin structure. The results obtained with a large set of subvisual parameters indicated significant differences in nuclear and chromatin features between the smear patterns of investigated groups. One important implication of these studies is that computerized image analysis of simply prepared tongue smears enables one to recognize subvisual HIV-related changes before clinical evidence of HL appears. PMID- 8213639 TI - More advanced-stage tumors among smokers with endometrial cancer. AB - To determine whether endometrial cancer is unusually aggressive in smokers, smokers were compared with nonsmokers among 157 women who had undergone hysterectomy for these tumors between 1979 and 1988. The following factors were analyzed: tumor stage and grade, duration of tumor-related symptoms, host age, degree of obesity, use of estrogen supplementation, and smoking habits. Multivariate analysis indicated that women with advanced-stage disease (stages II IV) more often had been smokers than women with early-stage disease (stages 0-I; 12 of 30 [40%] versus 14 of 127 [11%], respectively; odds ratio, 5.38; confidence interval, 2.23-11.31). Smokers and nonsmokers were similar in age, parity, degree of obesity, use of estrogen supplementation, tumor grade, and duration of symptoms. Advanced-stage disease also was associated with a high tumor grade (odds ratio, 3.16). Among women with early-stage tumors, a trend toward more frequent myometrial invasion in smokers was not significant by conventional criteria. These observations apparently reflect a smoking-related decrease in the incidence of early-stage tumors, plus smoking-related increases in tumor invasiveness and metastasis. PMID- 8213640 TI - DNA analysis (ploidy) of molar pregnancies with image analysis on paraffin tissue sections. AB - Hydatidiform moles can be subclassified based on their ploidy. In general, complete moles are diploid, and partial moles are triploid. The standard method for the determination of DNA content is flow cytometric analysis. In this study, the authors investigated whether static cytometric analysis with the CAS 200 Image Analyzer (Cell Analysis Systems, Inc., Elmhurst, IL) with a software program designed for quantitation of nuclear DNA content in tissue sections can be used to classify moles. Tissue sections from 17 moles were analyzed with this system, and the results were compared with those obtained with flow cytometric analysis. It was found that cell selection was an important factor. A high proportion of the hyperplastic trophoblast was in G2M. Exclusion of these areas and measurement of the trophoblast lining the villi only led to reliable results, and complete agreement between the results of the two methods was obtained. The findings indicate that cytometric analysis on tissue sections is a reliable alternative to flow cytometric analysis for the designation of moles as diploid or triploid. PMID- 8213641 TI - A comparative study of DNA quantitation in breast carcinoma with image cytometric analysis and in vitro fine-needle aspiration with flow cytometric analysis. AB - The DNA ploidy status of 53 fresh primary breast carcinomas was analyzed in a comparative study of flow cytometric (FCM) and image cytometric (ICM) analyses. Samples for FCM analysis were obtained with an in vitro fine-needle aspiration technique. Touch imprints from the same tumors were analyzed by three independent observers by ICM analysis. An ICM comparative study of "sequential" and "visually selected" nuclei also was performed. There was an overall concordance of 0.85 in the classification of diploid and nondiploid tumors by FCM and ICM analyses. In most discordant cases, a nondiploid population was identified by FCM analysis alone. This is attributed to the superior resolution of and sampling/preparatory method used for FCM analysis. There was an overall concordance of 0.91 in the classification of diploid and nondiploid tumors by ICM analysis. Selective analysis of atypical nuclei resulted in increased sensitivity in the detection of DNA aneuploid populations by ICM analysis. PMID- 8213642 TI - More on intravascular lymphomatosis. PMID- 8213643 TI - Cell Dyn 3000 and Coulter STKS automated differential counters. PMID- 8213644 TI - Large granular lymphocytosis and NK-associated expansions of CD3+ CD4- CD8+ type. PMID- 8213645 TI - Acculturation and delinquent behavior among Cuban American adolescents: toward an empirical model. AB - Uses data derived from a study of 6th- and 7th-grade Cuban American adolescents in the greater Miami, Florida, area. The effects of immigrant cultural adjustment on the behavior of adolescents, especially deviant behavior, has been a subject of interest for decades. However, heretofore, little empirical research has been conducted. Key findings indicate that family factors are related to the development of attitudes favoring deviance, whereas acculturation conflicts are associated with delinquent behavior. Results are considered tentative but important for developing a comprehensive and theoretically grounded model of factors contributing to deviant behavior among Hispanic adolescents. PMID- 8213646 TI - Ethnic group differences in vulnerability to parental alcoholism and life stress: a study of Hispanic and non-Hispanic Caucasian adolescents. AB - Tested Hispanic and Caucasian adolescents' vulnerability to parental alcoholism and life stress. Sixty-nine Hispanic and 237 Caucasian adolescents completed measures of life stress, social support, and alcohol use. Their parents reported on the adolescents' psychological symptoms and their own alcohol and substance use. Parental alcoholism and life stress were related to almost all indicators of adolescents' psychological distress and alcohol use. In addition, results showed some evidence that Caucasian adolescents were more vulnerable to the effects of life stress and parental alcoholism than Hispanics. Neither social support nor the higher substance use of Caucasian parents provided a good explanation for this differential vulnerability. PMID- 8213647 TI - Describing the homeless mentally ill: cluster analysis results. AB - Presented descriptive data on a group of homeless, mentally ill individuals (N = 108) served by a two-site demonstration project, funded by NIMH. Comparing results with those from other studies of this population produced some differences and some similarities. Cluster analysis techniques were applied to the data, producing a 4-group solution. Data validating the cluster solution are presented. It is suggested that the cluster results provide a more meaningful and useful method of understanding the descriptive data. Results suggest that while the population of individuals served as homeless and mentally ill is quite heterogeneous, many have well-developed functioning skills--only one cluster, making up 35.2% of the sample, fits the stereotype of the aggressive, psychotic individual with skill deficits in many areas. Further discussion is presented concerning the implications of the cluster analysis results for demonstrating contextual effects and thus better interpreting research results from other studies and assisting in future services planning. PMID- 8213648 TI - Presentation of the James E. Brophy AAO Distinguished Service Award. PMID- 8213649 TI - Sten Linder-Aronson receives the 1993 Albert H. Ketcham Award. PMID- 8213650 TI - Comment on Roth appliance. PMID- 8213651 TI - Comment on nonextraction treatment. PMID- 8213652 TI - Long-term effect of treatment with the headgear-Herbst appliance in the early mixed dentition. Stability or relapse? AB - In this investigation of the long-term effect of mandibular protrusive function in children with severe Class II malocclusions, a group of children age 8 years 8 months were initially treated for 5 months with a headgear-Herbst appliance followed by a 3- to 5-year period of activator retention. The patients were studied out of retention at the mean age of 17 years 4 months and compared with an untreated control group. Part of the sagittal correction relapsed. As compared with the control group, the average 3.9 mm protrusive effect of treatment on the mandible decreased to a nonsignificant 1.5 mm out of retention. The significant 2.0 mm therapeutic increase of the condylion-gnathion distance decreased to 1.3 mm and was not significantly different from control values at age 17 years 4 months. However, the 1.5 mm posterior effect of treatment on the maxilla continued to increase during activator retention and the difference compared with the control group was 2.3 mm postretention. This effect on the maxilla partly compensated the relapse tendency observed in the mandible so that 3.8 mm of the 5.4 mm posttreatment sagittal improvement still remained out of retention. Because of the sample size and individual variability, the results should be interpreted cautiously, but the findings indicate that maxillary sutural remodeling might be more receptive long-term to orthopedic treatment than the mandibular condylar growth process. PMID- 8213653 TI - Growth of mandibular prognathism after pubertal growth peak. AB - This study deals with the growth changes of the Japanese face associated with mandibular prognathism during 3 years after the pubertal growth peak. The investigation was based on the serial lateral cephalometric roentgenograms of prognathic and normal males and females, respectively. Maturational stages of the pubertal growth were determined individually by the ossification events taken from hand-wrist radiographs. Results indicate that the morphologic characteristics of the mandibular prognathism, which are established before the pubertal growth peak, are strongly maintained during the period studied. However, mandibular prognathism seems to show a manner of growth change fairly similar to that of the normal after the pubertal growth peak. PMID- 8213654 TI - Effect of head posture on cephalometric sagittal angular measures. AB - The definitions of cephalometric landmarks include relative terms that are dependent on the orientation of the head (e.g., lowest, most posterior) and head orientation differ widely during cephalometry (e.g., Frankfort plane horizontal, natural head posture). The purpose of this study was to quantify the effect of head posture changes on the commonly used sagittal angular measures SNA, SNB, and SNPogonion (SNPg). The sample comprised 30 Chinese skulls. Cephalograms were taken in a purpose designed skull holder with the Frankfort plane horizontal and at +10 degrees, +20 degrees, +30 degrees, -10 degrees, -20 degrees, and -30 degrees. A geometric grid was used to locate the deepest landmarks, and the landmarks were digitized followed by computer superimposition on the S-N line. To compare the values of the SNA, SNB, and SNPg angles in the different head postures, t tests were used. Head (skull) posture changes produced significant effects on the cephalometric values even at +/- 10 degrees of tilting. Overall, the angles were underestimated by approximately 1 degrees. In general, the angular differences and their standard deviations increased as the skull rotation increased with most of the differences for the SNB and the SNPg angles being clinically significant and also statistically significant at the 0.1% level. It was concluded that head posture needs to be standardized during cephalometry. Changes in posture significantly affect the location of some landmarks and the subsequent data obtained. PMID- 8213655 TI - The interaction between soft tissues and the sagittal development of the dentition and the face. AB - The purpose of this study was to investigate whether there are relationships between the cross-sectional surface area (CSSA) of the lips and the sagittal structure of the skeletal parts of the face and the dentition in the midsagittal plane and whether the sagittal structure of the face and the dentition is related to the class of malocclusion. The CSSA of the upper and lower lip was measured with a planimeter on the lateral cephalograms of 156 patients before their orthodontic treatment with a closed lip relation in rest. They were divided into 18 groups according to their age, sex, and Angle classification. The Quick Ceph program (Orthodontic Processing, Chula Vista, Calif.) was used to digitize and analyze 23 dental and skeletal parameters. The parameters were tested by an analysis variance to show differences between the three classes of malocclusion. The regression analysis was used to look for relations between the CSSA and the skeletal or dental parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213656 TI - Subtraction radiography to assess reproducibility of patient positioning in cephalometrics. AB - Subtraction radiography is a way to measure differences in landmark positions between cephalometric films without using tracings that introduce another source of error. This method was used to evaluate the reproducibility of head positioning in 54 pairs of cephalometric films taken within hours of each other, before and after splint removal in orthognathic surgery patients. There were no statistically significant changes in two cranial and four maxillary landmarks; the expected changes in mandibular landmark served to validate the method. The results suggest that patient positioning is not a major contributor to the error of cephalometric methods. PMID- 8213657 TI - Comparisons of the five analytic reference lines of the horizontal lip position: their consistency and sensitivity. AB - One-hundred ten lateral facial profiles were judged to be attractive and were selected from 1000 Taiwanese pupils by a panel of four men and three women from different educational backgrounds. The 110 in the attractive group were analyzed by using five analytic reference lines: Ricketts E line, Holdaway's H line, Steiner's S1 line, Burstone's B line, and Sushner's S2 line. Comparisons of the "consistency" (the smaller coefficient of variation the better the consistency) and the "sensitivity" (the power to differentiate the attractive lateral facial profiles from the unattractive ones) of the five analytic lines were performed. The B line was found to be best in terms of both consistency and sensitivity. From the point of view of convenience, the E line is of great value because its anterior location makes it convenient for the clinician to use. However, the B line appears best from the perspective of the value of reference. This study found that those analytic reference lines that do not transverse an anatomic landmark of the nose most likely have poor consistency and sensitivity. This finding is consistent with the idea that the nose should be taken into consideration when a line is to be used as a reference for beauty on the lateral facial profile. PMID- 8213658 TI - The effects of extraction versus nonextraction orthodontic treatment on the growth of the lower anterior face height. AB - The effect of orthodontic treatment on the lower anterior face height (ANS-Me) is of fundamental importance to the orthodontist. However, the choice between the two main methods of treatment, extraction versus nonextraction, is not clear cut. It is believed that the extraction method decreases ANS-Me, whereas nonextraction methods result in an increase in ANS-Me. This study examined the effects of both methods on ANS-Me for a sample of 174 subjects divided equally between Class I and II malocclusions. Most studies controlled for growth by using subjects in the same age group. However, we controlled for the effects of growth by normalizing ANS-Me measurements to the Michigan Growth Standard. With this method, we can compare subjects who differ in terms of the age at which treatment was started, as well as subjects whose treatments were of different duration, thereby enlarging the sample size. In addition to growth and duration of treatment, other factors like the effects of treatment choice and treatment mechanics were considered. The results obtained show that nonextraction treatment in Class I and II subjects is associated with a significant increase in the lower anterior face height. However, extraction treatment is not associated with any significant change in ANS-Me. PMID- 8213659 TI - Prediction of the size of unerupted canines and premolars in a Saudi Arab population. AB - The estimation of the size of unerupted permanent teeth is an essential aspect in treatment planning in the mixed dentition. The commonly used prediction methods of Moyers and Tanaka and Johnston are based on data from a sample of children of Northern European descent. The accuracy of these methods when applied to a different population is questionable. When we applied the Moyers probability tables to a limited sample of a Saudi Arab population, we found that the 35% level was a more accurate determinant than the commonly used 75% confidence level. Likewise, the prediction equations of Tanaka and Johnston overestimated the size of buccal segments in this population. The data illustrate the limitations of these methods when applied to a sample population of other than European descent. From this data, two linear regression equations were developed for tooth size prediction in Saudi Arab children. PMID- 8213660 TI - Force decay of elastomeric chain--a serial study. Part II. AB - This study was designed to evaluate the relaxation of elastomeric chain over time. The purposes were to compare the force decay curves of three variously stretched lengths, as well as to compare transparent and grey elastomeric chains. The elastomeric chains were fixed on a stainless steel framework that was submerged in 37 degrees C water bath for 6 weeks. The elastic forces of the chains were measured by a Dial-Type dynamometer, and recorded at the initial activation, first hour, eighth hour, twenty-fourth hour, third day, and then weekly to 6 weeks. The stretched length of the chains were decreased 0.5 mm per week. The results showed: (1) The sequence of stretch force at each time measurement of the Rocky Mountain clear energy chain was 40 mm > 35 mm > 30 mm. However, the percentage of remaining force was 40 mm < 35 mm < 30 mm. (2) The remaining force and the percentage of remaining force of the American Orthodontic short transparent chain were greater than the remaining force of the gray chain. (3) The remaining force and the percentage of remaining force of the Rocky Mountain clear chain with 40 mm stretch were greater than that of the American Orthodontic transparent and grey chains. (4) The effective force for canine retraction (184 gm) can be maintained by the Rocky Mountain energy chain with 40 mm, 35 mm, and 30 mm stretch for about 3 weeks, 1 week, and 3 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213661 TI - Correlates of objective patient compliance with removable appliance wear. AB - Patient compliance is considered a major problem in orthodontics. Yet, to date, few conclusive findings have been noted on determinants and consequences of failing adherence, probably because of method flaws and a lack of objective criteria. By following an outline of conceptual issues and selected research, we considered an investigation into correlates of patient compliance with removable appliance wear. We studied a sample of 77 university clinic patients ages 9 to 14 years over several months by means of psychologic inventories and electronic measurement of removable appliance wear. The actual compliance rate proved to be associated with many variables. Among those, characteristics of the patient and his family background, such as conformity and degree of consistent parental support and supervision are interpreted as determinants of satisfactory adherence, whereas treatment related and interactional correlates, such as duration of treatment, dominance of provider, and interpersonal perceptions, are conceived of in terms of mutually interdependent and/or consequent variables. The factors identified might be paralleled in the wearing of headgear and intraoral elastics that require a similar degree of active patient cooperation. After a critical discussion of our data in the light of previous findings, suggestions are provided for future research along with conclusions for clinical practice. PMID- 8213662 TI - The role of the headgear calendar in headgear compliance. AB - This study was undertaken to determine the role of the headgear calendar and its relationship to headgear compliance. Headgear timers were used covertly to monitor actual headgear wear of 28 patients for three consecutive orthodontic appointments. Fourteen patients were asked to monitor their daily headgear wear by using a headgear calendar. The other 14 did not use a calendar. The results show that patients who monitor their headgear wear with a headgear calendar are more compliant than those patients who do not (7.9 hours compared with 5.3 hours). All age groups in this study wore their headgear more when a headgear calendar was used with the exception of the > 16-year-old group. There is a high degree of correlation (r2 = 0.60) between the number of hours recorded on the calendar compared with the number of hours actually worn. There was a poor correlation (r2 = 0.02) between the number of hours the patient said he wore his headgear compared with the actual number of hours worn. PMID- 8213663 TI - Robert J. Isaacson. PMID- 8213664 TI - Growing up in the golden age of orthodontics. PMID- 8213665 TI - An American Board of Orthodontics case report: the surgical-orthodontic management of a Class I malocclusion with excessive overbite and periodontal bone loss. PMID- 8213666 TI - Automate your word processing system with three shell macros. PMID- 8213667 TI - Sexual harassment: an issue in the orthodontic office? PMID- 8213668 TI - The dangers of illegal child labor. PMID- 8213669 TI - Race and infant mortality. PMID- 8213670 TI - Intrauterine meconium aspiration in an extremely premature infant. PMID- 8213671 TI - Brucellosis presenting as prolonged fever and hemophagocytosis. PMID- 8213672 TI - Accidental strangulation of a toddler involving a wall light switch. PMID- 8213673 TI - Deaths at work among children and adolescents. AB - OBJECTIVE: To identify and describe all nonmilitary on-the-job injury fatalities in North Carolina among persons younger than 20 years over 10 years, with special attention to potential violations of the Fair Labor Standards Act. DESIGN AND SETTING: Historical, population-based case series, with cases identified by the computerized files of the North Carolina Office of the Chief Medical Examiner. CASES: Persons younger than 20 years who died of injuries received on the job in North Carolina between January 1, 1980, and December 31, 1989. RESULTS: We identified 71 cases. Decedents ranged in age from 11 to 19 years, with 41% aged 17 years or younger. Cases were disproportionately male (90%), white (80%), and injured during June, July, and August (44%). Farm or field was the most frequent place of injury (27%). More than 50% of injuries involved a motorized vehicle, frequently a tractor. Similar to studies in adults, homicide was the leading cause of fatal occupational injury for females. At the time of injury, 86% of workers younger than 18 years were involved in activities that appeared to violate the Fair Labor Standards Act of 1938. CONCLUSIONS: This study raises questions about the adequacy of federal child labor policies as minors continue to work under conditions that place them at risk for fatal injuries. PMID- 8213674 TI - Caudal duplication syndrome. AB - OBJECTIVE: To present the clinical and roentgenographic features of caudal duplication syndrome. DESIGN: Retrospective review of the medical records and all available imaging studies. SETTING: Two university-affiliated teaching hospitals. PARTICIPANTS: Six children with multiple anomalies and duplications of distal organs derived from the hindgut, neural tube, and adjacent mesoderm. INTERVENTIONS: None. RESULTS: Spinal anomalies (myelomeningocele in two patients, sacral duplication in three, diplomyelia in two, and hemivertebrae in one) were present in all our patients. Duplications or anomalies of the external genitalia and/or the lower urinary and reproductive structures were also seen in all our patients. Ventral herniation (in one patient), intestinal obstructions (in one patient), and bowel duplications (in two patients) were the most common gastrointestinal abnormalities. CONCLUSIONS: We believe that the above constellation of abnormalities resulted from an insult to the caudal cell mass and hindgut at approximately the 23rd through the 25th day of gestation. We propose the term caudal duplication syndrome to describe the association between gastrointestinal, genitourinary, and distal neural tube malformations. PMID- 8213675 TI - Self-perception of infertility among female adolescents. AB - OBJECTIVE: To determine the prevalence and correlates of the self-perception of infertility among female adolescents. DESIGN: Cross-sectional survey. SETTING: Urban adolescent clinic in a neighborhood health center in Denver, Colo. PARTICIPANTS: Two hundred sexually active, nulliparous, 14- through 18-year-old female adolescents. MEASUREMENTS/MAIN RESULTS: Concerns about fertility were expressed by 43 (21.5%) of the 200 respondents. Logistic regression analysis revealed that the factors most strongly associated with the self-perception of infertility were as follows (odds ratios; 95% confidence interval): a history of discussing infertility with anyone (4.3; 1.8 to 10.4); desire for pregnancy (3.8; 1.4 to 10.3); boyfriend desiring pregnancy (3.0; 1.1 to 8.3); a history of sexually transmitted disease(s) (3.0; 1.2 to 7.1); and having an older boyfriend (2.6; (1.1 to 6.2). Adolescents who doubted their fertility used contraceptives less frequently than other teens (30% vs 55% of the time; P < .01). CONCLUSIONS: The self-perception of infertility is common among sexually active urban female adolescents and may pose another barrier to contraceptive use. Our findings may help clinicians counsel adolescents about contraceptives more effectively. PMID- 8213676 TI - Prolactin-secreting macroadenomas in adolescents. Response to bromocriptine therapy. AB - OBJECTIVE: To report five cases of prolactin (PRL)-secreting macroadenomas in adolescents, including their presentations and responses to bromocriptine mesylate treatment. PATIENTS: Five adolescents (three females and two males) aged between 12.5 and 17 years were diagnosed as having PRL-secreting macroadenomas at the pediatric endocrine service at New York University Medical Center between 1987 and 1989. Presenting complaints included visual field deficits, gynecomastia, and amenorrhea, both primary and secondary. All patients demonstrated some feature of hypogonadism or pubertal arrest. Diagnostic criteria included an elevated serum PRL level (mean, 1670 micrograms/L; range, 610 to 3700 micrograms/L) and visualization of a pituitary tumor that measured greater than 1 cm by either a computed tomographic scan or magnetic resonance imaging (mean size, 2.7 cm; range, 1.4 to 4 cm). INTERVENTIONS: Each patient was treated with bromocriptine mesylate at an oral dose of 7.5 mg/d. The patients continued with that treatment for the duration of the study period. MEASUREMENTS AND RESULTS: Anterior pituitary function was evaluated in four of five patients before treatment. All four were growth hormone deficient. Three patients were also gonadotropin deficient. Thyrotropin (thyroid-stimulating hormone) and corticotropin (adrenocorticotropic hormone) deficiencies were demonstrated in three patients who had multiple pituitary deficits. Follow-up testing included serial PRL measurements and radiographic imaging of tumor size. All patients demonstrated a marked decrease in PRL levels, as well as in tumor size (mean shrinkage, 70%). The three patients who initially had visual field deficits showed significant improvement of vision with bromocriptine therapy. Follow-up study of anterior pituitary function showed significant improvement with bromocriptine treatment in three patients. CONCLUSIONS: Bromocriptine was quite effective in the shrinkage of PRL-secreting macroadenomas in all our patients. It is a noninvasive treatment that can preserve and restore vision, as well as pituitary function, which is integral to continued growth and sexual maturation of the adolescent. Bromocriptine is preferable to surgery or radiation in the treatment of PRL-secreting macroadenomas in the adolescent. PMID- 8213677 TI - Firearms and adolescent suicide. A community case-control study. AB - OBJECTIVE: To assess the association between firearms in the home and adolescent suicide. RESEARCH DESIGN: Matched, case-control. SETTING: Population-based community sample. SUBJECTS: Sixty-seven adolescent suicide victims and a demographically matched group of 67 living community controls. SELECTION PROCEDURE: The series of adolescent suicide victims was consecutive, with an overall participation rate of 74% (67/91). MEASUREMENTS AND RESULTS: The presence, type (hand-gun vs long-gun), number, and method of storage (locked vs unlocked, loaded vs unloaded) of firearms in the home were compared between the suicide victims and controls. Even after adjusting for differences in rates of psychiatric disorders between suicide victims and controls, the association between suicide and both any gun (odds ratio [OR] = 4.4, 95% confidence interval [CI] = 1.1 to 17.5) and handguns (OR = 9.4, 95% CI = 1.7 to 53.9) in the home were both highly significant. Long-guns in the home were associated with suicide only in rural areas, whereas handguns were more closely associated with suicide in urban areas. Handguns (OR = 12.9, 95% CI = 1.5 to 110.9) and loaded guns (OR = 32.3, 95% CI = 2.5 to 413.4) in the home were particularly significant risk factors for suicide in those with no apparent psychiatric disorder. CONCLUSIONS: When pediatricians are faced with a suicidal adolescent, they should insist on the removal of firearms from the home. Pediatricians should also inform parents that the presence of firearms may be associated with adolescent suicide even in the absence of clear psychiatric illness. PMID- 8213678 TI - Neonatal hemochromatosis associated with maternal autoantibodies against Ro/SS-A and La/SS-B ribonucleoproteins. AB - Liver disease in the fetus and neonate may be associated with maternal Sjogren's syndrome (neonatal lupus erythematosus). The infant of a mother with Sjogren's syndrome and high anti-Ro/SS-A and anti-La/SS-B antibody titers presented at 2 1/2 weeks of age with overwhelming hepatic insufficiency and died at 6 weeks of age. Autopsy confirmed the antemortem diagnosis of neonatal hemochromatosis. We discuss the possibility of a relationship between these two conditions. PMID- 8213679 TI - Effect of weight loss by obese children on long-term growth. AB - OBJECTIVE: To assess height growth over 10 years in children treated for obesity. DESIGN: Longitudinal, prospective follow-up of a series of randomized, controlled weight control trials. SETTING: Specialized pediatric weight control clinic. PARTICIPANTS: One hundred fifty-eight 6- to 12-year-old obese children who were followed up for 10 years after treatment. INTERVENTIONS: Family-based behavioral weight control. MEASUREMENTS/MAIN RESULTS: At entry the height percentiles of the obese children were significantly higher (71.6 percentile) than same-sex parent (52.0 percentile) or midparent (51.5 percentile) height (an estimate of parental contribution to height). After an average growth of 22.7 cm, children were 2.2 cm taller than their same-sex parent and decreased to an average height percentile of 57.8. Multiple regression analysis showed that child sex, age, baseline height and percent overweight, midparent height, and height change of the child from baseline to 5 years accounted for 94% of the variance in growth. Child percent overweight change made no contribution to predicting height change. Comparison between children obese and nonobese at 10 years showed no differences in growth. CONCLUSIONS: Moderate energy restriction with dietary guidance by overweight children did not negatively influence long-term growth. PMID- 8213680 TI - Missed opportunities in preventive pediatric health care. Immunizations or well child care visits? AB - OBJECTIVE: To determine the percentage of patients in a large pediatric practice in compliance with national recommendations regarding immunizations and well child care visits. RESEARCH DESIGN: Chart review. Point estimates with 95% confidence intervals were determined for reviewed charts in compliance with recommendations of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention and schedule of well-child care visits, screening, and anticipatory guidance recommended by the American Academy of Pediatrics (AAP). SETTING: A large, multisite urban public pediatric practice. PATIENTS: Three hundred eighty-six infants and children (aged 0 to 60 months) who had a total of 7595 patient visits. SELECTION PROCEDURE: A random sample of charts. RESULTS: There was a large discrepancy in compliance for patients aged 0 to 23 months in ACIP-recommended immunizations (90.5% +/- 3.9%) vs AAP recommended well-child care visits (37.6% +/- 6.4%) and for patients aged 24 to 60 months in ACIP-recommended immunizations (87.8% +/- 5.1%) vs AAP-recommended well-child care visits (31.0% +/- 7.1%). CONCLUSIONS: The data suggest that immunization alone does not ensure that children will receive all aspects of preventive care, raising questions about the practicality of the current AAP recommendations for preventive pediatric health care. PMID- 8213681 TI - Birth-weight-specific infant mortality risks and leading causes of death. Illinois, 1980-1989. AB - OBJECTIVE: To describe birth-weight-specific differences in mortality risks between white and black Illinois infants by age at death and leading cause of death. DESIGN: Population-based birth cohort study. SETTING: State of Illinois. PATIENTS: All Illinois infants who were born from 1980 through 1989 and reported to the Illinois Department of Public Health. The death certificates of these infants were matched to corresponding birth certificates using a computerized linkage algorithm. INTERVENTIONS: None. RESULTS: The high black infant mortality rate is attributable to higher mortality risks in the neonatal period for black, normal birth-weight infants and in the postneonatal period for all black infants, regardless of birth weight. CONCLUSION: Efforts to narrow the black-white gap in infant mortality and to reduce black mortality should not be limited to reduction of low birth weight and premature birth in black infants but should also include efforts to reduce risk factors associated with mortality among normal birthweight black infants. PMID- 8213682 TI - Child abuse, sudden infant death syndrome, and unexpected infant death. AB - There is now evidence, from a variety of approaches, that indicate that between one tenth and one fifth of children currently diagnosed as cases of sudden infant death syndrome are not natural deaths. There is also equally strong evidence, where the possibility of filicide has been explored, that the majority of children diagnosed as cases of sudden infant death syndrome do die of natural causes. PMID- 8213683 TI - Are febrile seizures provoked by a rapid rise in temperature? AB - Pediatricians are frequently taught that a rapid rise in temperature is responsible for causing a febrile seizure; yet there are no clinical data to support this hypothesis. The few experimental data are based on hyperthermia induced seizures in animals and are of no clear relevance to naturally occurring fevers and accompanying seizures. Further, the experimental findings are not consistent across studies. By contrast, there is substantial evidence indicating that the height of temperature plays a role in eliciting a febrile seizure. Although febrile seizures are now recognized as benign and, in general, a disorder that should not be treated with chronic anticonvulsant therapy, an understanding of how fevers lead to febrile seizures may be useful for evaluating the appropriateness and efficacy of treatments that involve intermittent therapy given at the time of fever. PMID- 8213684 TI - Children with unrecognized human immunodeficiency virus infection. An emergency department perspective. AB - OBJECTIVE: To provide an approach toward the diagnosis of children with human immunodeficiency virus (HIV) infection in the acute care setting. DESIGN: Patient reports and review of recent literature. SETTING: Emergency departments or acute care clinics. SELECTION PROCEDURES: Analysis of important recent clinical publications. INTERVENTIONS: None. RESULTS AND CONCLUSIONS: The clinical and historical findings associated with pediatric HIV infection are occasionally subtle and differ from those findings in adults. In this article, we have divided the first presentation of HIV in the acute care setting into five categories: recurrent bacterial infections, failure to thrive, unexplained organomegaly, adolescents with HIV, and late presentation of perinatally acquired HIV. Each category is illustrated by a patient treated in the acute care setting. Recognition of these categories of presentation will hopefully assist acute care physicians in the early diagnosis of HIV infection. PMID- 8213685 TI - Critical evaluation of the 2-minute orthopedic screening examination. AB - OBJECTIVE: To determine the sensitivity and specificity of the 2-minute, 12-step, orthopedic screening examination. DESIGN: Prospective, single-blind study. SETTING: National Collegiate Athletic Association Division 1 athletics program. PARTICIPANTS: Two hundred fifty-nine male and female varsity athletes. INTERVENTIONS: The athletes were screened by five primary care physicians who were "blind" to each patient's history. The athletes were then evaluated by a team of orthopedic surgeons who had knowledge of each patient's history. Significant injuries were injuries that would limit participation, predispose to injury, or need further evaluation or rehabilitation. MAIN RESULTS: A total of 120 significant injuries were identified by compiling the results of the history and both physical examinations. Of the significant injuries, 91.6% were detected by history alone. Fourteen of the significant injuries were missed by the detailed orthopedic examination, but they were detected by the screening examination. The overall sensitivity of the screening examination compared with the results of all three methods was 50.8%, with a specificity of 97.5%, positive predictive value of 40.9%, and negative predictive value of 98.3%. Almost half of the false-positive screening findings were shoulder asymmetries. CONCLUSIONS: Even in mass screenings, the screening orthopedic examination should be used only in conjunction with an orthopedic history. Some modifications may improve the sensitivity of the screening examination. PMID- 8213686 TI - Radiological cases of the month. Juvenile nephronophthisis. PMID- 8213687 TI - Radiological cases of the month. Presacral ganglioneuroma. PMID- 8213688 TI - Picture of the month. Cerebral malaria. PMID- 8213689 TI - Pathological cases of the month. Accessory tragus. PMID- 8213690 TI - Pathological cases of the month. Dystrophic calcification. PMID- 8213691 TI - Social networks and methadone treatment outcome: the costs and benefits of social ties. AB - OBJECTIVE: This study assessed the impact of social ties on substance abuse treatment outcome. Two models which predict alternative hypotheses were evaluated. 1) Based on the self-medication model, it was hypothesized that social support would aid in coping with painful affect and decrease the need for drugs. 2) Based on a social learning model, it was hypothesized that drug use in the social network would threaten abstinence due to modeling and conditioning effects. METHOD: Seventy methadone maintenance patients were given baseline measures of mood, stress, social support, and drug use in the network and followed prospectively for 3 months with weekly urine drug screens. RESULTS: Social support was correlated with positive affect (r = .59, p < .001), and stress with negative affect (r = .46, p < .001), but no measures of social support, affect, or stress correlated with the proportion of drug positive urines. However, patients with at least one drug user among the closest significant others had 63 +/- 38% positive urines versus 35 +/- 36% positive among those without a drug-using significant other (t = -3.2, p < .002). CONCLUSIONS: Substance use in the social network had a substantial negative impact on treatment outcome. Consistent with the social learning model and the traditional "persons, places, and things," this suggests interventions should get drug-using significant others into treatment and teach patients coping skills to reduce their negative influence. PMID- 8213692 TI - Toward a comparative overview of dependence potential and acute toxicity of psychoactive substances used nonmedically. AB - A procedure is outlined for comparing dependence potential and acute toxicity across a broad range of abused psychoactive substances. Tentative results, based on an extensive literature review of 20 substances, suggested that the margin of safety ("therapeutic index") varied dramatically between substances. Intravenous heroin appeared to have the greatest risk of dependence and acute lethality; oral psilocybin appeared to have the least. Hazards due to behavioral deficits, perceptual distortion, or chronic illness were not factored into the assessments. PMID- 8213693 TI - Social competence among cocaine abusers: moderating effects of comorbid diagnoses and gender. AB - Levels of social competence and maladaptive behaviors were examined among 184 male and 85 female treatment-seeking cocaine abusers. Social competence was assessed based on indices of functioning at work and in relationships, maladaptive behaviors included severity of drug and legal problems, and difficulties in interpersonal relationships. Consistent with developmental interpretations, results indicated that addicts with comorbid depression had higher social competence than those with comorbid antisocial personality disorders. In contrast with research on other psychiatric groups, female addicts had lower social competence than males; however, they also had lower levels of maladaptive behaviors. Findings are discussed in terms of implications for preventive interventions and treatment for drug abusers. PMID- 8213694 TI - HIV infection and i.v. drug use: medical examiner cases in Essex and Hudson Counties, New Jersey. AB - Patterns of HIV infection and IV drug use in 697 Essex and Hudson Counties, New Jersey, 1986-1987 Medical Examiner (ME) cases, aged 15-59 years, were examined. All cases had toxicology tests for drugs and had been autopsied. Postmortem stored sera were blind-tested and confirmed for the presence of HIV-1-antibody by the New Jersey Department of Health. All cases and IV drug users were dichotomized according to the presence/absence of HIV-1-antibody and were then analyzed for differences in demographic and postmortem characteristics. Subjects were predominantly Black men aged 30-44 years; the 119 HIV(+) cases were even more likely to be Black or Hispanic and in the 30-44 age group. Evidence of IV drug use and HIV(+) status were very highly correlated; 86 of 181 IV drug users were HIV(+). There was a low rate of suicide among HIV(+) cases and IV drug users. Only 3 of 63 suicide victims were HIV(+), and they were the only IV drug users whose manner of death was certified as suicide. Cases with toxicology findings of both heroin and cocaine were most likely to be HIV(+), followed in order by those with heroin or cocaine alone present. Cocaine alone was the illicit drug most often present in toxicology tests on all cases. Among IV drug users, heroin with cocaine was most often present. PMID- 8213695 TI - LIGHT model: an effective intervention model to change high-risk AIDS behaviors among hard-to-reach urban drug users. AB - Two thousand thirty-three hospital emergency room (ER) patients who were current, active injecting drug users (IDUs) were voluntary participants in a pretest, posttest research project which utilized a nursing model, the Personalized Nursing LIGHT Model, as a counseling approach to decrease high-risk AIDS behaviors. The LIGHT Model works by directly improving well-being and thereby indirectly decreasing high-risk behaviors associated with AIDS. Addicts from an urban ER in each of three cities (Detroit, Michigan; Brooklyn, New York; and Baltimore, Maryland) were treated with teams consisting of nurses and indigenous outreach workers. Posttest data were gathered on 995 of the clients who received the Personalized Nursing LIGHT Model teaching and counseling intervention. In a posttest at least 3 months after the initial interview, these IDUs reported a significant increase in well-being, t(530) = -11.77; p < .001, and significant reductions in frequency of IV heroin use, z = -18.4; p < .001, IV cocaine use, z = -16.0; p < .001, and IV speedball use, z = -14.3; p < .001, as well as significant decreases in sharing of cookers (a type of drug-using equipment), z = -13.8; p < .001, and other high-risk behaviors associated with AIDS acquisition and transmission. At a second posttest, at least 6 months after the initial interview, these results were unchanged. PMID- 8213696 TI - Elevated serum CK in long abstinent cocaine abusers. AB - In preparation for an exercise program in cocaine abusers maintained abstinent in a hospital setting (average 98.4 days), we measured resting serum creatine kinase (CK). Surprisingly, many were elevated. Further tests confirmed the observation. We measured 19 long abstinent cocaine abusers, 22 abstinent abusers of other substances, and a later group of 26 long abstinent cocaine abusers. While none of the other substance abusers showed elevated serum CK levels, 53 and 31% of the abstinent cocaine groups did (p = .000082 and .00041, respectively). All CK elevations were muscle derived; repeated sampling demonstrated stability. Cocaine abusers' CK showed a bimodal distribution: the lower bell curve approximated controls and the higher bell curve centered above normal range, at 400 U/L. Demographics did not influence the results. With complementary findings of impaired spatial motor performance, these persistent CK elevations suggest that a large minority of cocaine abusers maintain tendencies to coarse motor control and impulsive movements, and perhaps hyperactivity. PMID- 8213697 TI - Religiosity and drug abuse among psychiatric inpatients. AB - Clinical impressions and data from a limited number of studies suggest that membership in certain groups such as Alcoholics Anonymous may promote well-being and abstinence from alcohol and drugs. The present study examines measures of religiosity and drug/alcohol consumption in an inpatient psychiatric population in order to test the possible association between these variables. One hundred sixty-eight adult admissions to a private psychiatric hospital were asked to complete the Religious Involvement Questionnaire (RIQ), a self-report instrument containing validated measures of intrinsic and extrinsic religiosity. Responses of general adult psychiatric patients (N = 103) were compared with those of patients admitted to a chemical dependence unit (N = 65). Correlations between alcohol/drug use and RIQ responses were measured for the entire sample. Patients admitted for chemical dependence were significantly less likely than general adult psychiatry patients to avoid certain food/music/drink because of their religion, and were less likely to help with the running of their church. Measures of alcohol, hallucinogen, and prescription drug consumption had significant negative correlations with religiosity scores. Chemically dependent patients differ from psychiatric patients with other diagnoses on measures of religiosity. Religious belief and involvement may be clinically relevant variables in the treatment outcome of chemically dependent patients. PMID- 8213698 TI - Morbidity risk for alcoholism and drug abuse in relatives of cocaine addicts. AB - The morbidity risks for alcoholism in the first-degree relatives of a cohort of male cocaine addicts with or without alcoholism comorbidity were studied. Of the 71 patients who participated in our study, 40 (56.3%) had a history of alcoholism and 37 (59.1%) a history of opioid abuse. Twenty-two patients (30.1%) also met criteria for a lifetime diagnosis of a major psychiatric disorder. Significant increases in morbidity risks for alcoholism were found among male relatives of cocaine addicts with comorbid alcohol dependence when compared with relatives of cocaine addicts with no alcohol comorbidity. Among fathers, risks were .69 vs .32 (z = 2.98, p < .003). Among brothers, risks were .38 vs .15 (z = 2.35, p < .03). Significantly increased risks were also observed in male relatives when probands with a psychiatric diagnosis were excluded from the analyses. Among female relatives, increases in morbidity risks were found but they failed to reach statistical significance. Two interpretations are consistent with these findings. One of these interpretations is that alcoholism is a disorder distinct from other addictions and has its own mode of transmission. The second interpretation is that the transmission of substance use disorders lacks specificity and that the substances selected are influenced by sociocultural or biological factors. PMID- 8213699 TI - Substance abuse among subjects screened out from an alcoholism research program. AB - Three hundred and eight subjects were screened over the phone for admission to an inpatient alcohol treatment research unit. Using a structured interview, the prospective patients were asked questions regarding demographics, drinking history, previous treatments, physical health, family history, and a detailed history of past and present substance use. Drug use was studied as regular use versus no use or brief experimental use of five drug categories: cannabinoids, stimulants, sedatives, opiates, and hallucinogens. Fifty-one percent of the men and 48% of the women reported regular use of one or more of the drugs in addition to alcohol. For women, the amount of alcohol intake was positively correlated with use of stimulants (r = .32, p = .001), cannabinoids (r = .24, p = .019), sedatives (r = .30, p = .003), and hallucinogens (r = .30, p = .003). For men, correlations between the amount of alcohol intake and drug use were weaker but significant for stimulants (r = .21, p = .002), opiates (r = .15, p = .028), and hallucinogens (r = .15, p = .029). Women with alcoholic mothers displayed higher alcohol intake than women with nonalcoholic mothers (p = .02) and also showed more frequent use of most drugs. Although men with alcoholic fathers also showed greater alcohol intake compared to men with nonalcoholic fathers, the two groups did not differ in drug use. Younger subjects of both sexes were more likely to use cannabinoids, stimulants, opiates, and hallucinogens. Alcohol and sedative use was relatively constant across all age groups. PMID- 8213700 TI - Alcohol-related blackouts in a medical practice. AB - One hundred thirty-five individuals seeking help for an alcohol or drug problem from a family physician completed a self-report questionnaire. Eighty-six percent of respondents reported having experienced alcohol-related blackouts. Blackouts were found to be most strongly related to severity of alcohol problems. They were not clearly early-stage nor middle-stage indicators of alcohol problems and were not associated with a variety of neuropsychological indicators. PMID- 8213701 TI - Clinician assessment of psychiatric comorbidity and alcoholism severity in adult alcoholic inpatients. AB - Although psychiatric comorbidity and alcoholism severity are risk factors for poor outcomes in treating alcoholism, little is known about whether clinicians assess these conditions accurately. In this study we evaluated four clinicians' assessments of two indicators of alcoholism severity and three psychiatric co morbidities in 78 inpatients in their third to seventh day of hospitalization in alcohol treatment programs. Clinicians overestimated the number of days drinking in 28% of subjects, and the number of drinks per drinking day in 37% of subjects. Clinicians underestimated alcohol consumption for patients with higher incomes. Clinicians correctly diagnosed 67% of 18 subjects with antisocial personality disorder, 65% of 26 with major depression, and 89% of 28 with drug abuse. These preliminary results need to be replicated in larger samples of clinicians to determine whether interventions are needed to improve the recognition of important prognostic factors in the treatment of alcoholic patients. PMID- 8213702 TI - Hospital resource utilization by American Indians/Alaska Natives for alcoholism and alcohol abuse. AB - Previous work examining the issue of alcoholism and alcohol abuse among American Indians and Alaska Natives can be broadly categorized as either descriptions of the consumption patterns and behaviors of specific tribes or mortality studies, focusing on deaths due to alcoholism, alcohol abuse, chronic liver disease, or cirrhosis. A major shortcoming of previous studies has been that they have not looked at the burden this problem has imposed upon the system of health care delivery for this minority population. By using an International Classification of Diseases, Ninth Revision, Clinical Modification taxonomy of diagnostic codes developed by the National Institute on Alcoholism and Alcohol Abuse (NIAAA) and the national Indian Health Service (IHS) inpatient database for direct and contract admissions, utilization patterns for 43 IHS facilities were investigated. The period of study was 1980-1988, and our case definition included any individual 14 years and older who had any mention upon discharge of an alcohol-related diagnosis (ARD). For the 9-year period under investigation, 43,302 adult inpatient admissions occurred at the 43 IHS facilities for ARD. These admissions accounted for an overall estimated per annum rate of 13.7% of the adult inpatient days. In addition, age and gender specific discharge rates for ARD were estimated and compared to reported ARD discharge rates of the United States civilian population prepared by the NIAAA using the National Hospital Discharge Survey over the period 1979-1988. In contrast, the IHS discharge rates for ARD were three times greater than reported ARD discharge rates for the United States civilian population. PMID- 8213703 TI - Multi-phase chemoprevention of large bowel carcinogenesis. PMID- 8213704 TI - Gastroesophageal reflux disease: the roles of motility in pathophysiology and therapy. PMID- 8213705 TI - NSAID effect on sporadic colon polyps. AB - In this study, our objective was to determine whether 6 months of open-label therapy with sulindac 400 mg/daily or piroxicam 20 mg/daily promote regression of adenomatous colonic polyps left in situ. Left-sided colonic polyps (size 3-12 mm) detected at colonoscopy were measured and left without being biopsied. The bowel wall opposite to the polyps was marked with India ink submucosally. Patients were assigned to drug therapy, and compliance was determined by pill count. Polyps were measured during sigmoidoscopy after 3 and 6 months of treatment; polyps were removed at the 6-month examination. Examiners were not blinded to drug therapy or previous polyp measurements. Seven patients completed 6 months of therapy (five sulindac and two piroxicam). Two additional patients treated with piroxicam were withdrawn secondary to adverse events (bleeding gastric ulcer and rash). In one patient treated with sulindac, a 6-mm polyp disappeared, and two other polyps seemed to regress partially. One polyp regressed partially in a piroxicam-treated patient. All other polyps remained unchanged. CONCLUSIONS: We did not observe dramatic regression of sporadic colon adenomatous polyps to either sulindac or piroxicam after 6 months of therapy in this small uncontrolled pilot study. PMID- 8213706 TI - Effect of single and repeated doses of metoclopramide on the mechanisms of gastroesophageal reflux. AB - Decreased lower esophageal sphincter pressure, transient relaxations of the lower esophageal sphincter, and acute increases in intra-abdominal pressure are among the most common pathogenic factors in gastroesophageal reflux. This study examines the effect of metoclopramide on these factors in patients with gastroesophageal reflux disease. Six patients with clinical and endoscopic evidence of esophagitis underwent esophageal manometry and intraesophageal pH monitoring over a 5-h period (1 h basal, and 4 h postprandially). The study was done on three different days: on day 1, after placebo, on day 2, after 10 mg po metoclopramide (order randomized), and on day 3, after metoclopramide 10 mg po quid for 7 days. Metoclopramide given for 1 wk significantly increased the basal lower esophageal sphincter pressure as compared to placebo and a single dose (p < 0.05). It also significantly decreased reflux episodes during the 3rd and 4th hour postprandially when given both as a single dose or after 1 wk of treatment. There was no significant difference in the other parameters measured. Repeated metoclopramide doses decrease reflux episodes in patients with reflux esophagitis by increasing basal lower esophageal sphincter pressure and possibly by accelerating gastric emptying. PMID- 8213707 TI - Update on the medicinal management of phytobezoars. AB - The purpose of this review article is to provide the clinician with complete information concerning available medicinal agents for the management of phytobezoars. Data sources were obtained by a Medline search from 1966 to present. All citations containing references to patients with a phytobezoar treated with medicinal agents were selected and reviewed for treatment regimen, number of patients treated, length of therapy, success rate, and adverse effects. A total of 36 patients with phytobezoars were reviewed. Papain was successful in treating 87% (13 of 15) and cellulase in 100% (19 of 19) of the patients. Adverse effects reported in the papain group were gastric ulcer, esophageal perforation, and hypernatremia; the cellulase group did not report any adverse effects. Papain and cellulase appeared to be effective in the management of phytobezoars in the small number of patients studied. However, controlled clinical trials are needed to compare the safety and efficacy of the two agents. PMID- 8213708 TI - Antibiotic therapy for bacterial enterocolitis: a comprehensive review. AB - The treatment of bacterial enterocolitis is a major health care issue throughout the world. Many cases of diarrhea due to invasive bacterial pathogens can be managed by oral rehydration, only. Nonetheless, antibiotics play an invaluable role in the management of patients suffering from severe diarrhea or extraintestinal symptoms. This article reviews the literature supporting current recommendations for antibiotic therapy. PMID- 8213709 TI - Colonic toxicity of administered medications and chemicals. AB - Although medication-induced colonotoxicity is uncommon, it is important that it be recognized, because the initial therapy for this condition is medication discontinuation. This review categorizes the association between the listed medications and colonotoxicity as "well-established" or "probable," according to the following criteria: number of clinical studies by independent clinical investigators, total number of reported cases, plausibility of an association based on experimental and pharmacologic studies, and validity of an association in each reported case. Medications associated with colonic ischemia include cocaine, ergotamine, estrogen, amphetamines, digitalis, methysergide, and vasopressin. Medications associated with colonic pseudoobstruction include narcotics, phenothiazines, vincristine, atropine or other anticholinergics, ganglionic blocking agents, and tricyclic antidepressants. Medications promoting infectious or necrotizing enterocolitis include numerous antibiotics associated with pseudomembranous colitis, deferoxamine associated with Yersinia enterocolitis, chemotherapy associated with neutropenic colitis, and hyperosmolar medications or formulas in infants. Medications associated with an allergic, inflammatory, or cytotoxic colitis include gold compounds, nonsteroidal antiinflammatory drugs, alpha-methyldopa, flucytosine, methotrexate, salicylates, and sulfasalazine. Potassium chloride, administered in slow-release wax matrices, can cause intestinal ulcers. Chronic cathartic use leads to colonic hypomotility and abdominal distention. Methysergide can cause a colonic stricture due to retroperitoneal fibrosis. Intrarectally administered compounds that have produced a toxic colitis include powerful acids, bases, and other corrosives. Enemas using hypertonic radiographic contrast agents have been associated with colitis in patients with colonic obstruction. PMID- 8213710 TI - Endoscopic transpapillary biopsy for diagnosis of patients with pancreaticobiliary ductal strictures. AB - We used recently developed biopsy forceps to acquire transpapillary tissue in a consecutive series of 43 patients with pancreaticobiliary ductal strictures found during endoscopic retrograde cholangiopancreatographic examinations. There were 19 cholangiocarcinomas, 15 pancreatic carcinomas, five benign biliary, and four benign pancreatic ductal strictures. Tissue sampling from the strictures was successful in 41 patients (95.3%), without complications. All specimens were adequate for histologic evaluation. Eighty-one percent of the patients with carcinomas were diagnosed histologically by this technique. Sensitivity was 88% for cholangiocarcinoma and 71% for pancreatic carcinoma. There were no false positive results. We conclude that transpapillary biopsy, being a simple, safe, and convenient method, should be applied as an initial diagnostic means during endoscopic retrograde cholangiopancreatography. PMID- 8213711 TI - The effect of ursodeoxycholic acid therapy on gallstone formation in the morbidly obese during rapid weight loss. AB - Obesity is a significant risk factor for cholesterol gallstone formation, particularly when patients are morbidly obese and rapidly losing weight. Our objective, in a double-blind, placebo-driven trial of ursodeoxycholic acid, was to study the prevention of gallstone development in 29 morbidly obese subjects after bariatric surgery. These subjects included 20 women and nine men, ages 43 +/- 7.3 yr, weight 142.5 +/- 31 kg (mean +/- SD), representing 224% +/- 28.2% of their ideal body weight. Gallbladders were free of stones according to preoperative ultrasound and palpation at surgery. Microscopy of aspirated gallbladder bile revealed cholesterol crystals present in only one patient. After recovery from vertical-band gastroplasty, 13 patients received ursodeoxycholic acid 1000 mg/day. Ten patients completed the 3-month study: two were noncompliant, one experienced heartburn. Fourteen of 16 subjects on matching placebo also were compliant; two were not. There were no differences in clinical characteristics or bile composition between these two groups on entry into the study. The cholesterol saturation index in these obese patients at 1.62 +/- 0.46 was definitely supersaturated, and higher than that in 10 non-obese patients without stones (0.96 +/- 0.29) or 10 with pigment stones (1.01 +/- 0.28) (p < 0.05). At 3 months, the two obese groups had similar weight loss (17% of preoperative weight) and had repeat ultrasounds. Six of the 14 placebo-treated patients (43%) developed gallstones: two became symptomatic, requiring cholecystectomy. There was no correlation between the risk of developing gallstones and pretreatment bile composition or the degree of weight loss. None of 10 patients or ursodeoxycholic acid formed gallstones. CONCLUSIONS: Morbid obesity is associated with gallbladder bile supersaturated with cholesterol. A high percentage will develop gallstones following gastroplasty. This can be prevented by ursodeoxycholic acid therapy. PMID- 8213712 TI - Fundic gland polyps: prevalence and clinicopathologic features. AB - We evaluated prospectively all gastroscopic examinations performed at two institutions for a period of 24 months with the aim of studying fundic gland polyps in our patient population. Forty-four patients with fundic gland polyps of the stomach were identified among 5554 patients who underwent endoscopy, for a prevalence of 0.8% in our patient population. Twelve additional patients with fundic gland polyps were identified through our surgical pathology referral practice. The patients' ages ranged from 27 to 82 yr, with an average age of 53 +/- 13 yr. The vast majority of the patients were female, with a female-to-male ratio of approximately 5:1. The polyps averaged 2.3 +/- 1.2 mm in size. An average of four polyps per patient were seen, with a range of one to 11. PMID- 8213713 TI - Gastric dysplasia. A follow-up study. AB - Gastric dysplasia is generally accepted as a precancerous lesion. Ninety-nine patients with an initial diagnosis of gastric dysplasia, based on examination of endoscopic biopsies taken because of symptoms of dyspepsia, were followed to define the magnitude of the neoplastic risk. The degree of dysplasia in the initial biopsy was mild in 73 cases, moderate in 16, and severe in 10. Mild dysplasia was no longer detected in 74% of patients, persisted in 19%, and progressed in 7% (in four cases, to carcinoma). Moderate dysplasia regressed to mild dysplasia in 31% of cases, it was no longer found in 56%, and progressed to cancer in 13%. Our data show that both lesions can progress slowly, although in most instances they remain stable or regress. Thus, annual endoscopic and histologic controls appear to be advisable. Severe dysplasia was no longer detected in 20% of cases, regressed to moderate in 10%, persisted in 10%, and progressed to cancer in 60%; in half of these patients, carcinoma was detected within 3 months. Thus, severe dysplasia indicates a high risk of cancer, often a synchronous one, and it requires gastrectomy when it persists in repeated biopsies. PMID- 8213714 TI - Computer-assisted fluorescence identification of colon cancer in rats. AB - Hematoporphyrin derivative (HPD) fluorescence is highly sensitive in identifying colon cancers in the rat. Its specificity, however, is compromised by HPD accumulation in lymphoid follicles. We developed a computer-assisted method to distinguish lymphoid from malignant tissue using HPD fluorescence. Colon cancer was induced in rats by weekly injections of 1,2-dimethylhydrazine. Twenty-four hours after intravenous HPD injection, the animals were sacrificed and the colonic surface was illuminated with a blue light (340-410 nm). Computer images were examined for characteristic patterns of fluorescence at 632 nm. The ratio of fluorescence intensity between lesions and adjacent background areas was also determined. The fluorescent areas were then coded and examined histologically. Eighty-one lesions (21 cancers, 60 lymphoid follicles) were identified. Only two lesions (one cancer, one lymphoid follicle) were incorrectly identified using computer images (concordance rate = 98%). The lesion:background fluorescence ratio was higher in malignant tissue than lymphoid follicles, but significant overlap was seen. These results indicate that computer-enhanced images of HPD fluorescence can distinguish malignant from lymphoid tissue in the rat colon and may have a potential role in the diagnosis of colon cancer. PMID- 8213715 TI - A role for culture in diagnosis of Helicobacter pylori-related gastric disease. AB - In this study, our objective was to determine the presence of Helicobacter pylori and other rapid urease-positive (RUP) organisms in gastric biopsies in 70 patients, 30 of whom had ulcers or erosions. A retrospective chart review was undertaken to correlate diagnostic tests (culture and direct urease) with results of endoscopic examination and the patient's clinical information. Eleven of 70 (15.7%) patients' biopsies were positive by both culture and direct urease for H. pylori, seven (10%) patients' biopsies were positive by culture only, and eight (11.4%) biopsies by direct urease only. Of 30 patients with ulcers (esophageal, antral, stomach, or duodenal), 15 had evidence of H. pylori infection by culture and/or direct urease test. In addition, patients with a positive direct urease test but a negative culture for H. pylori were more likely to have other rapid urease-positive organisms (RUP) isolated from their gastric biopsy cultures than patients with negative results from both tests. CONCLUSIONS: As a result of problems associated with commonly used diagnostic tests, a combination of tests performed on multiple biopsies is more sensitive and specific for the diagnosis of H. pylori infection than any single test. The common occurrence of RUP streptococcal and staphylococcal species in gastric biopsy tissue is demonstrated and proposed as a cause of false-positive direct urease tests. PMID- 8213716 TI - A comparison of the effect of olestra and triglyceride on postprandial esophageal acid exposure. PMID- 8213717 TI - Clinical and nutritional factors predictive of plasma lipid unsaturation deficiency in advanced liver cirrhosis: a logistic regression analysis. AB - AIM: To identify those clinical and nutritional factors associated with plasma lipid unsaturation deficiency in cirrhosis. METHODS: Fatty acid profiles of plasma phospholipids (PL) and cholesteryl esters (CE) were measured in 101 inpatients with advanced cirrhosis and in 44 age- and sex-matched healthy controls. Double-bond index (DBI) was calculated for each fraction and binarily categorized in each patient using the 5th percentile of the control group as the cut-off limit. The association of 12 routine clinical, biological, and nutritional variables with derangement of each DBI was multivariately assessed by means of stepwise logistic regression analysis. RESULTS: The DBI of PL and CE were below the 5th percentile of the control group in 60 and 68 of 101 cirrhotic patients, respectively. After multivariate analyses, the variables found to be independent predictors of impaired unsaturation were: 1) The presence of moderate/severe malnutrition (odds ratio: 1.3-8.0 (95% CI); p < 0.05) and serum tau-GT > 1 mukat/L (odds ratio: 0.2-1.0; NS) for plasma PL, and 2) the presence of moderate/severe malnutrition (odds ratio: 1.8-17.4; p < 0.05), serum bilirubin > 50 mumol/L (odds ratio 1.7-14.5; p < 0.05) and serum tau-GT > 1 mukat/L (odds ratio 0.1-1.1; NS) for CE. CONCLUSION: Malnutrition appears to be a major factor for impaired lipid unsaturation in advanced cirrhosis. Thus, the possibility of improving plasma lipid unsaturation in these patients by means of nutritional support should be further investigated. PMID- 8213718 TI - Circulating growth hormone and insulin-like growth factor-I in nonalcoholic liver cirrhosis with or without superimposed hepatocarcinoma: evidence of an altered circadian rhythm. AB - Adult liver is considered the major source of circulating insulin-like growth factor-I (IGF-I). Growth hormone (GH) exerts its effects by stimulating IGF-I release from the liver, which then mediates the somatogenic actions in target tissues. In turn, circulating IGF-I levels operate a negative feedback mechanism on GH release. In cirrhotic patients, single daily determinations, performed after an overnight fast, indicated that serum IGF-I are decreased, whereas GH levels are increased. To verify whether this phenomenon occurs through the 24-h period, we have studied the profiles of GH and IGF-I in cirrhotic patients with or without superimposed hepatocellular carcinoma (HCC) and in a group of control subjects. The results of the present studies suggest that in cirrhotic patients, the above changes are constantly present through the 24-h period, and are associated with a loss of circadian rhythm for both GH and IGF-I. These data are consistent with a failure of the liver to synthesize and release IGF-I in response to GH. In addition, the presence of constantly higher IGF-I levels in cirrhotic patients with superimposed HCC, compared with cirrhotic patients without HCC, raises the hypothesis of a causal relationship between IGF-I and the development of HCC. PMID- 8213719 TI - Effect of esophageal intraluminal mechanical and chemical stressors on salivary epidermal growth factor in humans. AB - Although various animal and clinical studies have demonstrated the significant effect of salivary epidermal growth factor (sEGF) on esophageal morphology and function, its secretory patterns still remain inadequately explored. Therefore, we have studied the impact of esophageal mechanical and chemical stimuli on sEGF in humans. sEGF was measured in saliva collected during basal conditions, chewing of parafilm, placement of esophageal tubing, inflation of intraesophageal balloons, and perfusion with NaCl, HCl, and HCl/pepsin solutions. The concentration of sEGF was measured with a radioimmunoassay kit from Amersham (Arlington Heights, IL). The concentration of sEGF in basal saliva was (mean +/- SEM) 2.08 +/- 0.22 ng/ml. Chewing the parafilm resulted in a significant decline of sEGF concentration to the value of 1.39 +/- 0.16 ng/ml (p < 0.0005). Similar decline in sEGF concentration also prevailed after placement of intraesophageal tubing (p < 0.03), and inflation of intraesophageal balloons (p < 0.01). This decline intensified significantly when prolonged esophageal perfusion with saline was implemented (p < 0.03 vs. tubing). Substitution of NaCl with HCl in the second and third perfusion periods prevented the decline in sEGF concentration, whereas HCl accompanied by pepsin enhanced sEGF concentration. The rate of sEGF output was 0.90 +/- 0.13 ng/min during basal conditions and increased significantly during parafilm chewing (1.53 +/- 0.25 ng/min; p < 0.05). However, sEGF secretion during both placement of esophageal tubing and inflation of balloons increased 4.1- and 4.9-fold, respectively (p < 0.002 and < 0.00005), over the basal value, and 2.4- and 2.9-fold, respectively, over the parafilm stimulated secretion. Subsequently, we observed a further significant decline of sEGF output (p < 0.05) which was sustained during perfusion of the esophagus with saline. Interestingly, esophageal perfusion with HCl prevented the decline of sEGF secretion observed during perfusion with saline. sEGF output during esophageal perfusion with HCl/pepsin exhibited a strong increase, reaching the value of 5.86 +/- 0.70 ng/ml. This value corresponds to a 58% increase over the secretory rate observed during mechanical stimulation by placement of esophageal tubing (3.71 +/- 0.47; p < 0.05). HCl/pepsin-induced potentiation of sEGF secretion was also highly significantly increased over both the value recorded during basal (p < 0.0005) and parafilm-stimulated (p < 0.002) conditions. Subsequent substitution of HCl/pepsin solution with a final saline perfusate still maintained enhanced sEGF output, compared with both basal (p < 0.02) and parafilm-stimulated conditions (p < 0.02).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8213720 TI - Exacerbation of psoriasis due to interferon-alpha treatment of chronic active hepatitis. AB - Interferon-alpha is an immune modulating drug which is indicated for the treatment of chronic viral hepatitis B and C. Several previous reports have suggested an association between treatment of patients with interferon-alpha and the development or exacerbation of autoimmune diseases. We report two patients with chronic viral hepatitis in whom treatment with interferon-alpha was associated with dramatic worsening of previously diagnosed psoriasis, necessitating discontinuation of the drug. PMID- 8213721 TI - Eosinophilic sclerosing cholangitis associated with hypereosinophilic syndrome. AB - We describe the case of a 41-yr-old man who presented with signs and symptoms of cholestasis including abdominal pain, jaundice, and fever, with peripheral eosinophilia of 10% and bone marrow eosinophilia. Liver biopsy revealed an eosinophilic infiltrate and an ERCP demonstrated bile duct changes, compatible with primary sclerosing cholangitis (PSC). After treatment with prednisone and ursodeoxycholic acid, the patient's liver profile tests returned to normal, the ERCP changes resolved, and all symptoms disappeared. A literature review has not shown any previous reports of reversible sclerosing cholangitis, secondary to eosinophilic infiltration. The purpose of this report is to describe eosinophilic cholangitis, an entity that mimics PSC in the context of the hypereosinophilic syndrome. PMID- 8213722 TI - Multistep, multicentric, and simultaneous development of hepatocellular carcinoma. AB - We resected a multiple hepatocellular carcinoma (HCC) which contained portal tracts, showed evidence of an early multistep condition, and a multicentric development of HCC which progressed simultaneously. A preoperative working examination revealed a tumor in S5 of the liver, which was 2.5 cm in diameter. In addition, a "nodule-in-nodule" appearance was seen on the ultrasonographic imaging. At intraoperative ultrasonography, an additional two HCCs were detected. At histologic examination of the resected specimen, the main nodule showed a nodule-in-nodule appearance. In the outer nodule, there was a well-differentiated HCC, while the portal tracts remained. The less-differentiated HCC grew in the inner nodule and was replacing the well-differentiated HCC in the outer nodule. These findings suggests morphological transition in the early stages of the multistep development of HCC. Two additional tumors (1.1 cm and 1.0 cm in diameter) detected at intraoperative ultrasonography proved to be HCCs (grade I) with marked fatty change, and with portal tracts remaining within both the HCCs. Furthermore, both of the HCCs retained their preexisting liver structure. These histologic findings coincided with the characteristics of the early stage HCC, whereas the coexistence of early stage HCCs suggests the multicentric development of HCC. Distortion, compression, and invasion of the portal tracts may appear as the tumor grows, thereby evoking an increasing risk of metastasis via the portal tracts. Therefore, the early diagnosis and treatment of HCC before the portal tracts disappear, when 1.5 cm in size or less, may be very important for surgeons and diagnosticians, as an effective curative resection may be feasible. PMID- 8213723 TI - Subhepatic appendicitis. PMID- 8213725 TI - Acute gastric volvulus: pathogenesis, diagnosis, and treatment. AB - A 61-yr-old women presented with vomiting, abdominal pain, and distention. Nasogastric and endoscopic decompression failed to relieve her distention. Radiographic studies suggested gastric necrosis without other pathology. Laparotomy revealed a rare form of mesenteroaxial volvulus of the fundus with frank necrosis. The patient underwent gastric resection with anterior gastropexy followed by an uncomplicated postoperative course. This paper discusses the etiology, anatomic definition, and therapeutic options in patients with acute gastric volvulus. PMID- 8213724 TI - Three-dimensional demonstration and endoscopic treatment of pancreaticoperitoneal fistula. AB - An alcoholic man presented with bloody ascites, which was confirmed as pancreatic ascites complicating chronic pancreatitis. Endoscopic retrograde pancreatography [ERP] demonstrated a ductal disruption at the head of the pancreas, a fistulous tract, and extravasation to the peritoneal cavity. Furthermore, a computerized tomographic scan subsequent to the endoscopic retrograde pancreatography (ERP-CT scan) gave the three-dimensional anatomy of the fistulous tract by the residual contrast media in the pancreatic duct and the fistulous tract. The pancreatic ascites, which was refractory to conventional medical treatment of a 5-wk duration, was successfully treated by endoscopic placement of a pancreatic stent and administration of a somatostatin analogue. PMID- 8213726 TI - Multicentric granular cell tumor of the colon: report of a patient with 52 tumors. AB - Granular cell myoblastoma is an uncommon benign tumor that can be located anywhere in the body. Multiple tumors of the gastrointestinal tract are quite rare, having been reported infrequently in the English literature. The histologic, immunohistochemical, and electron microscopic findings in our case, as well as in others reported, suggest that its histogenesis may be related to Schwann cells. One case of multifocal granular cell tumor presenting 52 tumors from the cecum to the sigmoid is described, and the previously reported cases with similar presentation are reviewed. We suggest that in such cases, a long period of observation with repeated colonoscopy may be more appropriate than an aggressive approach. PMID- 8213727 TI - The "brown bowel syndrome" associated with jejunal carcinoma. PMID- 8213728 TI - Familial stomach cancer. PMID- 8213729 TI - Celiac disease and tropical calcific pancreatitis. PMID- 8213731 TI - Pathological rupture of spleen in hepatitis B virus-related cirrhosis. PMID- 8213730 TI - Candida albicans cholecystitis. PMID- 8213732 TI - Zenker's diverticulum: new pieces to the pathogenesis puzzle. PMID- 8213733 TI - Benign versus malignant pancreatic cysts: seeing through the haze? PMID- 8213734 TI - Pancreatitis and CBD stones: when to seek and destroy. PMID- 8213735 TI - Flat feeding PEG button. PMID- 8213736 TI - Re: Positive tests for cytomegalovirus in AIDS patients. PMID- 8213737 TI - Identification and characterization of an ATPase system of Helicobacter pylori and the effect of proton pump inhibitors. PMID- 8213738 TI - Budd-Chiari syndrome associated with the hypereosinophilic syndrome. PMID- 8213739 TI - Rumination in a patient with achalasia. PMID- 8213740 TI - Electrocardiographic abnormalities in inflammatory bowel disease. PMID- 8213741 TI - Untreated blood pressure level is inversely related to cognitive functioning: the Framingham Study. AB - It was hypothesized that blood pressure would be inversely related to cognitive functioning, if unconfounded with antihypertensive medication and measured over many occasions prior to neuropsychological testing. For stroke-free Framingham Study participants aged 55-88 years (n = 1,702), blood pressure levels were averaged over five biennial examinations (1956-1964) when few hypertensives were being treated, and examined in relation to neuropsychological tests administered between 1976 and 1978. With age, education, occupation, cigarette smoking, alcohol consumption, and gender controlled, blood pressure levels and chronicity of hypertension were inversely related to the composite score and measures of attention and memory. This was true for the full sample, for a subsample untreated during blood pressure measurement (n = 1,485), and for a subsample untreated throughout the entire study period (n = 1,038). For example, decline per 10 mmHg increment in blood pressure ranged from -0.04 to -0.07 standard score units (z) for the composite score. A negative finding previously was most likely due to blood pressure measurement concurrently with neuropsychological testing, or too few measurements. Hypertension-associated pathogenic processes may cause mild cognitive impairment, but other mechanisms need to be considered. PMID- 8213742 TI - Modification of increasing systolic blood pressure in the elderly during the 1980s. AB - The authors examined whether changing attitudes and approaches to modifying blood pressure during the 1980s affected the previously described pattern of increasing systolic blood pressure in the elderly which continues through the ninth decade of life. In 1982-1983, a door-to-door census identified 4,497 community-dwelling residents of East Boston, Massachusetts aged 65 and over, of whom 3,657 had baseline blood pressure assessments. Follow-up blood pressure assessments occurred in 1985-1986 and in 1988-1989. Cross-sectionally, the relation of age with systolic blood pressure was quadratic with levels predicted to increase until about age 84 after which they were lower among oldest-old survivors. Longitudinally, mean age-sex-adjusted systolic blood pressure was 3.3 mmHg lower in 1985-1986 compared with 1982-1983 (95 percent confidence interval (CI) 2.4-4.2 mmHg) and 10.6 mmHg lower in 1988-1989 compared with 1982-1983 (95 percent CI 9.5 11.7 mmHg). Utilization of antihypertension medications increased over time and accounted for some, but not all, of the observed decreases in systolic blood pressure. Large shifts occurred in the use of specific antihypertension medications including increases in use of angiotensin converting enzyme inhibitors and calcium entry blockers and decreases in use of thiazide diuretics. Previously described trends for increasing systolic blood pressure in the elderly were reversed during the 1980s when the continued decline in cardiovascular mortality was greatest among the elderly. PMID- 8213743 TI - No association between caffeine intake and postmenopausal breast cancer incidence in the Iowa Women's Health Study. AB - The association of caffeine intake and postmenopausal breast cancer incidence was assessed among 34,388 Iowa women aged 55-69 years in 1986 and followed through 1990. Caffeine intake was assessed by a food frequency questionnaire. Median caffeine intake was 212 mg/day in women who developed breast cancer (n = 580) and 201 mg/day in women who remained free of the disease (p = 0.95). There was no apparent association between breast cancer occurrence and quintile of caffeine intake, either adjusted for age or for multiple breast cancer risk factors. The same was true for regular coffee and other caffeine-containing foods. PMID- 8213744 TI - Risk factors for injurious falls leading to hospitalization or death in a cohort of 19,500 adults. AB - Falls are the most common cause of nonfatal injuries and a major cause of injury death. In order to identify risk factors for injuries from falls, 19,518 persons aged 20-92 years from four regions of Finland were examined and followed up from between 1973 and 1977 to 1984 for 8 to 11 years by identifying hospital admissions or deaths due to fall injuries. During 187,405 person-years, 628 injuries from falls were documented. The risk for injuries from falls was significantly and independently of other factors associated with alcohol intake in all age and sex groups. After adjustment for all the other risk determinants, the relative risks (RR) (95% confidence intervals (CI)) in persons with monthly ethanol intake of 100-499 g, 500-999 g, and > or = 1,000 g were 1.43 (1.13-1.82), 2.32 (1.71-3.17), and 3.05 (2.05-4.55), respectively, compared with abstainers. Body mass index (kg/m2) > or = 30 was associated with an increased risk among women aged < 45 years (RR = 2.8, 95% CI 1.28-5.89), whereas in persons aged > or = 65 years it seemed to be a protective factor both among men (RR = 0.3, 95% CI 0.06-1.19) and women (RR = 0.5, 95% CI 0.30-0.76). Also single marital status, smoking, heavy physical activity during leisure time, use of psychopharmacologic agents, diabetes mellitus, and cardiovascular diseases other than stroke were found to carry independent predictive significance in at least one subgroup of sex and age. In conclusion, alcohol consumption, relative weight, and use of psychopharmacologic agents were seen to be the most relevant risk determinants. Intervention trials based on the predictive factors and on high-risk groups are needed. PMID- 8213745 TI - Old age and race as determinants of initiation of glaucoma therapy. AB - Demographic differences in the prevalence of blindness may be partly due to undertreatment of susceptible population subgroups. The authors examined the relation of age, race, and other demographic characteristics with initiation of treatment for glaucoma and compared treatment rates with expected rates based on known disease prevalence. Data were from Medicaid enrollees aged 65-99 years in New Jersey between March 1981 and February 1990. Based on review of all claims for prescription medications and laser and incisional surgery, there were 6,173 cases with at least 6 months of documented system eligibility before their initial treatment for glaucoma. The overall rate of new treatment was 11.5 cases per 1,000 person-years, and increased throughout the 1980s. The age-adjusted relative rate of new treatment was 1.58 times higher in blacks compared with whites; however, this was less than half the relative rate expected based on estimated relative incidence rates. Similarly, enrollees aged 70-99 years had only 7% to 27% higher treatment rates than those aged 65-69 years, substantially less than expected. Treatment for glaucoma was also less likely to be initiated in nursing home residents, compared with those living in the community. Blacks and the very old are much less likely to have treatment for glaucoma initiated than would be predicted based on the magnitude of disease burden in these populations. PMID- 8213746 TI - Oral polio vaccination during pregnancy: no increase in the occurrence of congenital malformations. AB - To examine the possible association between maternal vaccination with oral polio virus and congenital malformations of the child, use was made of a nationwide mass vaccination in Finland. During a restricted period in 1985, a vaccination with trivalent oral poliovirus was implemented with coverage of 94% of the population. The study population was chosen from three major hospitals in the Greater Helsinki Region in Finland which deliver over 95% of the children of their catchment area. One study and two reference cohorts were delineated; the former consisted of pregnancies that were in their first trimester during the vaccination period. The two reference cohorts included mothers from the same hospitals whose pregnancies were likewise in the first trimester during the corresponding time period in 1984 and 1986, i.e., 12 months before and after the study period. Each cohort consisted of approximately 3,000 mothers/children whose delivery and hospital records were manually perused by trained nurses. All the structural malformations reflecting an impaired organogenesis during the sensitive first trimester were monitored. A total of 209 (2.3%) such malformations were recorded and characterized. There were no differences between the study and reference cohorts (risk ratio = 0.7, 95% confidence interval 0.5 1.0). According to the authors' power estimate, an additional prevalence greater than 0.5% would have been detected. The authors conclude that administration of oral poliovirus vaccine during early pregnancy was not associated with an elevated risk of congenital malformations. PMID- 8213747 TI - Racial and ethnic differences in human immunodeficiency virus type 1 (HIV-1) seroprevalence among homosexual and bisexual men. The Multicenter AIDS Cohort Study. AB - To determine whether the excess prevalence of human immunodeficiency virus type 1 (HIV-1) infection in US black and Hispanic homosexual men relative to white men can be explained by differences in sociodemographic factors, history of sexually transmitted diseases, or sexual and drug-use behaviors, the authors conducted a cross-sectional analysis of baseline HIV-1 seroprevalence and HIV-1 risk factors among 4,475 non-Hispanic white, 234 Hispanic white, and 194 black homosexual men from four centers in the United States (Baltimore/Washington, DC, Pittsburgh, Chicago, and Los Angeles). HIV-1 seroprevalence was significantly higher in Hispanic men (50%; odds ratio (OR) = 1.83, 95% confidence interval (CI) 1.41 2.39) and black men (47%; OR = 1.62, 95% CI 1.21-2.16) compared with white men (35%). Both Hispanic and black men more frequently reported a history of sexually transmitted diseases. Overall, Hispanics had the highest risk profile and blacks the lowest risk profile with respect to certain high-risk sexual behaviors (e.g., receptive anal intercourse and use of anonymous sexual partners) and recreational drug use. After multivariate adjustment, black race remained a significant independent risk factor for HIV-1 seropositivity (OR = 1.60, 95% CI 1.13-2.26), but Hispanic ethnicity was no longer statistically significant (OR = 1.17, 95% CI 0.82-1.69). Most of the excess HIV-1 prevalent infection among Hispanics was explained by their predominant recruitment from Los Angeles--the study center with the highest HIV-1 seroprevalence--and their greater prevalence of a history of sexually transmitted diseases and certain high-risk sexual practices. By contrast, adjustment for these same risk behaviors failed to explain the observed black-white differences in HIV-1 seroprevalence, and further studies are needed to elucidate the reasons for these unexplained racial differences. HIV-1 educational programs for homosexual men should take into account the behavioral differences that exist between white and minority racial/ethnic groups. PMID- 8213748 TI - A Bayesian approach to measurement error problems in epidemiology using conditional independence models. AB - Risk factors used in epidemiology are often measured with error which can seriously affect the assessment of the relation between risk factors and disease outcome. In this paper, a Bayesian perspective on measurement error problems in epidemiology is taken and it is shown how the information available in this setting can be structured in terms of conditional independence models. The modeling of common designs used in the presence of measurement error (validation group, repeated measures, ancillary data) is described. The authors indicate how Bayesian estimation can be carried out in these settings using Gibbs sampling, a sampling technique which is being increasingly referred to in statistical and biomedical applications. The method is illustrated by analyzing a design with two measuring instruments and no validation group. PMID- 8213749 TI - Primary versus proxy respondents: comparability of questionnaire data on alcohol consumption. AB - Questionnaire data on alcohol consumption obtained from primary respondents participating in a community-based case-control study of coronary heart disease were compared with similar data obtained from their next of kin. The primary respondents were men and women aged 25-64 years who were a representative sample of myocardial infarction cases (n = 58) and controls (n = 456) from the case control study. The study was conducted in Auckland, New Zealand between 1986 and 1988. When alcohol drinking frequency was collapsed into five categories, exact agreement between primary respondents and next of kin was 64% for cases and 62% for controls. Agreement within one category (plus or minus) was 89% for both cases and controls. Tests of marginal homogeneity showed no evidence that next of kin systematically over- or underestimated the primary respondents' self-reported drinking frequency. With respect to the amount of alcohol drunk, mean differences between primary respondents and next of kin were small (mean difference: 2.25 g per day for cases; -0.77 g per day for controls), although there was considerable variability between individual pairs in the level of agreement. The findings suggest that studies which use proxy sources of data to assess alcohol drinking are unlikely to produce biased estimates of alcohol consumption at the aggregate level, particularly with regard to frequency measures. PMID- 8213750 TI - Misclassification bias arising from random error in exposure measurement: implications for dual measurement strategies. AB - Despite the resulting loss of information, continuous exposure variables are often categorized in epidemiologic data analysis. It has been shown that nondifferential measurement error of exposure can lead to differential misclassification under these circumstances. This paper extends these findings to the misclassification bias that results from nondifferential measurement error if dual measurement strategies are employed with dichotomized exposures. Different scenarios of random measurement error are presented in the context of case control studies. Although differences in the misclassification rates between cases and controls are generally small, the bias toward the null is usually much weaker than expected under truly nondifferential exposure misclassification even with single exposure measurements. In most cases, the bias is further reduced by the use of dual measurements. Caution is needed, however, if the analysis is restricted to individuals with concordant exposure classifications (both measurements above or both measurements below the cutpoint). In this case, the true exposure-disease association is often overestimated. PMID- 8213751 TI - Magnetic fields and cancer in children residing near Swedish high-voltage power lines. AB - A case-control study was conducted to test the hypothesis that exposure to magnetic fields of the type generated by high-voltage power lines increases cancer incidence in children. The study base consisted of everyone under age 16 years who had lived on a property located within 300 meters of any of the 220 and 400 kV power lines in Sweden during the period 1960-1985. Subjects were followed from their entry into the study base through 1985. A total of 142 cancer cases were identified through a record linkage to the Swedish Cancer Registry. There were 39 leukemia and 33 central nervous system tumor cases. A total of 558 controls were selected at random from the study base. Exposure was assessed by spot measurements and by calculations of the magnetic fields generated by the power lines, taking distance, line configuration, and load into account. Information about historical loads on the power lines was used to calculate the magnetic fields for the year closest in time to diagnosis. When historical calculations were used as exposure assessment for childhood leukemia with cutoff points at 0.1 and 0.2 microtesla (microT), the estimated relative risk increased over the two exposure levels and was estimated at 2.7 (95% confidence interval (CI) 1.0-6.3) for 0.2 microT and over; p for trend = 0.02. When the upper cutoff point was shifted to 0.3 microT, the relative risk was 3.8 (95% CI 1.4-9.3); p for trend = 0.005. These results persisted when adjustment for potential confounding factors was made. For central nervous system tumor, lymphoma, and all childhood cancers combined, there was no support for an association. PMID- 8213752 TI - Determinants of papillary cancer of the thyroid. AB - Determinants of papillary thyroid cancer were evaluated in a questionnaire-based case-control study from southeastern Sweden. A total of 104 cases, diagnosed from 1977 to 1987, and 387 randomly selected controls were included in the analyses. Female subjects with papillary cancer reported a work history as dentists/dental assistants, telephone operators, teachers, and day nursery personnel, and an occupational contact with chemicals and video display terminals more often than did controls. The 11 male cases more often reported working as mechanics and metal workers and having occupational contact with solvents. Other factors associated with increased risk for female papillary cancer were having private well water at the birth address; leisure time exposure to combustion smoke; low intake of cruciferous vegetables and seafood; and a family history of goiter, heart disease, biliary disorder, or female genital cancer. Diagnostic radiographic examinations, especially to the head, neck, or upper back/chest area, or repeated dental examinations, were also found to be associated with this form of cancer. With regard to the possible influence from hormonal factors among women less than age 50 years at time of diagnosis, an increased risk was found for a pregnancy soon after puberty. Tendencies toward a decreasing risk with increasing age at first pregnancy as well as an increasing risk with increasing number of pregnancies were found as well. Multiparity seemed to potentiate the effect from prior radiographic examinations. PMID- 8213753 TI - Case-control study of bladder cancer and water disinfection methods in Colorado. AB - A population-based case-control study of bladder cancer and drinking water disinfection methods was conducted during 1990-1991 in Colorado. Surface water in Colorado has historically been disinfected with chlorine (chlorination) or with a combination of chlorine and ammonia (chloramination). A total of 327 histologically verified bladder cancer cases were frequency matched by age and sex to 261 other-cancer controls. Subjects were interviewed by telephone about residential and water source histories. This information was linked to data from water utility and Colorado Department of Health records to create a drinking water exposure profile. After adjustment for cigarette smoking, tap water and coffee consumption, and medical history factors by logistic regression, years of exposure to chlorinated surface water were significantly associated with risk for bladder cancer (p = 0.0007). The odds ratio for bladder cancer increased for longer durations of exposure to a level of 1.8 (95% confidence interval 1.1-2.9) for more than 30 years of exposure to chlorinated surface water compared with no exposure. The increased bladder cancer risk was similar for males and females and for nonsmokers and smokers. Levels of total trihalomethanes, nitrates, and residual chlorine were not associated with bladder cancer risk after controlling for years of exposure to chlorinated water. PMID- 8213754 TI - Inconsistent associations of caffeine-containing beverages with blood pressure and with lipoproteins. The CARDIA Study. Coronary Artery Risk Development in Young Adults. AB - The authors examined associations of caffeine and caffeinated beverage intakes with blood pressure and with lipoproteins in 5,115 black and white men and women aged 18-30 years during 1985-1986. Caffeine and beverage intakes were not consistently associated with blood pressure in analyses controlling for race, sex, Keys score, sucrose intake, physical activity, oral contraceptive use, body mass index, alcohol use, age, and smoking. Associations of caffeine and beverage intakes with cholesterol, triglycerides, high-density lipoprotein cholesterol, and high-density lipoprotein2 cholesterol were also inconsistent. There is little or no association of caffeine with lipoproteins or with blood pressure in this cohort of healthy young adults. PMID- 8213755 TI - Long-term risk of hysterectomy among 80,007 sterilized and comparison women at Kaiser Permanente, 1971-1987. AB - To study the long-term risk of hysterectomy after tubal sterilization, the authors analyzed historical hospital discharge data on 39,502 parous women sterilized during 1971-1984 and 40,505 comparison women matched on age, race, parity, and interval since last birth. Sterilized women were significantly more likely than were comparison women to undergo hysterectomy (relative risk (RR) = 1.35, 95% confidence interval (CI) 1.26-1.44), especially for diagnoses of menstrual dysfunction and pelvic pain (RR = 1.88, 95% CI 1.65-2.13). Higher relative risks were not associated with greater tissue-destructive methods of tubal occlusion. Relative risks were highest for women who were young on the reference date (RR = 2.45, 95% CI 1.79-3.36 for women aged 20-24 years), but declined steadily as age increased (RR = 0.96, 95% CI 0.72-1.28 for women aged 40 49 years). In all age groups, relative risks were significantly above 1.00 after 7 years of follow-up. Reasons for elevated risks may be related to a greater willingness of sterilized women to forgo their uteruses. The emergence of greater risk in all age groups, however, prevents the authors from ruling out a possible latent biologic effect of tubal sterilization. PMID- 8213756 TI - Post-traumatic stress disorder in adolescents after a hurricane. AB - A school-based study conducted in 1990, 1 year after Hurricane Hugo, investigated the frequency and correlates of post-traumatic stress disorder (PTSD) in 1,264 adolescents aged 11-17 years residing in selected South Carolina communities. Data were collected via a 174-item self-administered questionnaire that included a PTSD symptom scale. A computer algorithm that applied decision rules of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised to the symptoms reported was used to assign a diagnosis of PTSD and to designate the number of individuals who met the reexperiencing (20%), avoidance (9%), and arousal (18%) criteria. Rates of PTSD were lowest in black males (1.5%) and higher, but similar, in the remaining groups (3.8-6.2%). Results from a multivariable logistic model indicated that exposure to the hurricane (odds ratio (OR) = 1.26, 95% confidence interval 1.13-1.41), experiencing other violent traumatic events (OR = 2.46, 95% confidence interval 1.75-3.44), being white (OR = 2.03, 95% confidence interval 1.12-3.69) and being female (OR = 2.17, 95% confidence interval 1.15-4.10) were significant correlates of PTSD. PMID- 8213757 TI - Factors associated with the decline in cirrhosis death rates among young adults in Allegheny County, Pennsylvania, 1973-1985. AB - From 1973 to 1985, the age-adjusted death rate from liver cirrhosis (International Classification of Diseases, Ninth Revision, code 571) dropped by 62.7% among adults aged 25-54 years in Allegheny County, Pennsylvania. The authors investigated factors associated with this decline by verifying causes of death on death certificates from medical records, coroner's reports, and autopsy reports. Although death rates from cirrhosis were slightly underestimated from death certificates, the underestimation did not alter the declining mortality trend. This decline in rates was significant after adjustment of the age, sex, and race effect using statistical modeling. No significant variability in the time trends was noted between sexes, races, and age groups. Neither did the trends in alcohol-related and "unspecified" cirrhosis differ. However, the trends varied significantly between the cirrhosis deaths certified by the coroner and by noncoroner physicians. From 1973-1975 to 1976-1978, the rate initially dropped by 51% among the coroner cases, whereas it dropped by only 9% among the noncoroner cases. By the period 1982-1985, the death rates of both coroner and noncoroner cases declined to approximately 50% of their 1973-1975 rates. These results suggest that the decline during the years 1973-1985 was real and that the trend was initiated by the pronounced decline during the early years in the coroner certified cirrhosis deaths. PMID- 8213758 TI - Seroprevalence of hepatitis B viral markers in 52,000 Alaska Natives. AB - As a part of a program to screen and immunize as many Alaska Natives as possible against hepatitis B infection, hepatitis B virus seromarkers were measured in 52,022 Alaska Natives between 1983 and 1987. Hepatitis B surface antigen (HBsAg) was found in 1,603 persons (3.1%), and 7,155 persons (13.8%) exhibited hepatitis B virus seropositivity. While the prevalence of total seropositivity increased with increasing age (p < 0.001), the proportion of seropositive persons who were also positive for HBsAg was significantly higher in children under age 5 years than in persons over age 60 (p < 0.001). The total hepatitis B virus seropositivity was significantly higher in males than in females (p < 0.001), and a greater proportion of seropositive males than seropositive females had HBsAg (p < 0.001). The prevalence of HBsAg and total seropositivity differed significantly by geographic region (p < 0.001), ranging from 0.5% to 8.2% for presence of HBsAg and from 5.4% to 29% for total seropositivity. Of persons who were HBsAg positive, hepatitis B e antigen was found in 35.4%, and antibody to hepatitis e antigen was found in 49.6%. The prevalence of hepatitis B e antigen significantly decreased with age, while that of antibody to hepatitis e antigen significantly increased. The prevalence of hepatitis B virus seropositivity is high in Alaska Natives, and there are significant differences in both the prevalence of HBsAg and total hepatitis B virus seromarkers by age, sex, and geographic region. PMID- 8213759 TI - Re: "Serum ceruloplasmin level and the risk of myocardial infarction and stroke". PMID- 8213760 TI - Re: "Increased mortality from brain tumors: a combined outcome of diagnostic technology and change of attitude toward the elderly". PMID- 8213761 TI - Re: "Childhood weight and growth rate as predictors of adult mortality". PMID- 8213762 TI - Growth retardation in homozygous sickle cell disease: role of calorie intake and possible gender-related differences. AB - To evaluate the possible role of inadequate food intake in the pathogenesis of the growth retardation of patients with sickle cell anemia, we determined the daily intake of calories and macronutrients and measured several anthropometric indices in 20 patients with sickle cell anemia aged 17-35 years and in 15 of their normal siblings of similar age. Compared to the control groups, the male patients, but not the females, had a significantly lower mean weight, body mass index, midarm circumference, and triceps and subscapular skinfold thicknesses. Also, while the male patients consumed significantly less total calories, proteins, carbohydrates, and fats per day than their control group, no difference was noted between the daily intake of calories or macronutrients in the female patients and their control group. However, when the intake of calories and macronutrients was corrected for body weight, there was no statistically significant difference between the intake of nutrients in the male patients and their control subjects or between the female patients and their control group. These results suggest a sex-related difference in the somatic growth of adolescent and adult patients with sickle cell anemia and also suggest that, although an inadequate food intake may be partly responsible for the impaired somatic growth in sickle cell anemia, other factors are also probably important. PMID- 8213763 TI - Recombinant interferon alpha-2b in the treatment of polycythemia vera. AB - We studied the effects of recombinant alpha 2-b interferon (alpha 2-b IFN) in a dose of 3 x 10(6)U intramuscularly three times a week for 1 year in 13 patients affected by polycythemia vera (PV) previously treated with phlebotomy only. Response to treatment was evaluated by reduction of the number of phlebotomies required to retain normal hematocrit value. Ten out of 13 patients (77%) responded to treatment; in 4 of them the exigency of phlebotomy was completely eliminated. In all responders a concomitant decrease of platelet count and splenomegaly was obtained. Treatment was well tolerated and side effects were easily controlled. We conclude that alpha-IFN may represent an attractive therapeutic option in the management of the proliferative stages of PV. PMID- 8213764 TI - Characterization of nondeletion alpha-thalassemia mutations in the Greek population. AB - alpha-Thalassemia is usually due to deletions within the alpha-globin gene cluster, leading to loss of function of one (-alpha) or both [-(alpha) or --] alpha-globin genes. Nondeletion mutations (denoted alpha alpha T or alpha T alpha) are less frequent and in Greece are not well defined. We report the analysis of 16 nondeletion alpha-thalassemia chromosomes using a polymerase chain reaction method to amplify specifically the alpha 2-globin gene, which was subsequently screened using ASO hybridization or restriction enzyme analysis for four mutations already characterized in other Mediterranean and Middle Eastern populations. Of the 16 nondeletion chromosomes, nine had the polyadenylation signal mutation (alpha PolyA alpha), two the IVSI 5' pentanucleotide deletion (alpha Hph alpha), two the Hb Icaria mutation (alpha Ic alpha), and one the initiation codon mutation (alpha Nco alpha). In two, the defects are still undefined. These findings show that nondeletion alpha-thalassemia in Greece is heterogeneous and that the most frequent mutation (accounting for > 50%) is the polyadenylation signal mutation, which to date was most commonly found in the Saudi Arabian population. PMID- 8213765 TI - Graft versus host anti-Rho(D) following minor Rh-incompatible orthotopic liver transplantation. AB - Hemolysis caused by ABO antibodies after ABO-compatible, nonidentical solid organ transplantation has been previously reported. The passenger B lymphocytes within the donor organ presumably generate an acute, primarily red cell-directed graft vs. host (GVH) response. Graft survival may also be compromised. GVH Rh antibodies have also been described, primarily in renal transplants. Only three cases, two only in abstract form, have been reported thus far describing GVH Rh antibodies in liver transplant patients, to which we add a fourth. A 62-year-old blood group A Rho(D)-positive woman with cirrhosis underwent orthotopic liver transplantation from a group A Rho(D)-negative, previously Rho(D)-sensitized donor and subsequently developed acute, self-limited hemolysis requiring four units of packed red cells. Anti-Rho(D) was identified in both serum and red cell eluate. An antibody detection test, identification, and assessment of the antibody reactivity score from the pretransplant donor specimen may identify patients at risk for hemolysis due to GVH Rh antibodies. PMID- 8213766 TI - Synergistic effect of heme and IL-1 on hematopoietic stromal regeneration after radiation. AB - Results from this study show that a combination of heme and interleukin-1 (IL-1) treatment resulted in the most improved recovery of hematopoietic-stromal regeneration after sublethal irradiation. Less pronounced effects were obtained when heme or IL-1 were given singly. Sublethal irradiation of mice produced an initial (as early as day 1) intense depression of the hematopoietic system as evidenced by leukopenia. In vivo treatment of animals with heme in combination with IL-1, accelerated hematopoietic and stromal regeneration as determined by hematopoietic spleen colony forming unit assay (CFU-S), erythroid (BFU-E), myeloid (CFU-GM) clonal cultures, long-term bone marrow cultures (LTBMC), and the ability to regenerate hematopoiesis by ectopic (renal) stromal hemopoietic transplantation. Sixteen days after irradiation, leukocyte levels in heme and IL 1 treatment groups were higher than non-treated animals and were near normal values by 27 days. One day after irradiation, the capacity of stromal progenitors to form new bone and hematopoietic cells (ectopic foci) was severely impaired, but recovered after 2-4 weeks. This recovery process was accelerated in heme and IL-1-treated animals. BFU-E, CFU-GM, and CFU-S capacity was also severely impaired in all animals 1-27 days after irradiation. CFU-S was only 0.15% of control by day 1 and 5% of control by day 16. Treatment with heme or IL-1 improved recovery by as much as 70% after 27 days of irradiation. A similar but enhanced recovery was seen for BFU-E and CFU-GM, with erythroid recovery the best. Total cellularity, adherent cell layer (ACL) formation, and clonogenic capacity by LTBMCs (10 weeks) derived from irradiated animals was severely reduced, whereas the hematopoietic capacity by LTBMCs derived from heme- and IL-1 treated animals had recovery values similar to non-irradiated controls. These results suggest therapeutic use of heme and IL-1 after chemotherapy or bone marrow depression may be beneficial. PMID- 8213767 TI - Tracing iron and transferrin in the macrophage by visual means. AB - The purpose of the study was to investigate the movement of iron and transferrin in the macrophage using light and electron microscopy. First, depicted here are the phagocytosis of antibody sensitized murine red cells by the murine bone marrow derived macrophage and the formation of red cell phagosomes. Second, we show the fusion of the lysosomes with the red cell phagosome to form a lysophagosome and the lysis of the red cell using acid phosphatase as a lysosome marker. Third by autoradiography, the presence of 55Fe silver grains in the phagocytosed red cells and its delivery to the organelles of the macrophage are demonstrated. Fourth a transferrin species is shown in red cells of all ages, in the phagocytosed as well as the non-phagocytosed, and in the phagocytosed as well as the non-phagocytosed, and in the macrophage itself. Transferrin was detected using immunogold and fluorescence labelling. These studies suggest that iron, using vesicles as means of transport, moves from the effete red cells inside the macrophage to the outside possibly bound to transferrin. PMID- 8213768 TI - Anticoagulant activity of an anti-beta 2-glycoprotein I antibody is dependent on the presence of beta 2-glycoprotein I. AB - We studied whether or not an anti-beta 2-glycoprotein I antibody (aGPI) had lupus anticoagulant-like activity, employing the diluted Russel viper venom time (dRVVT) and kaolin clotting time (KCT) as indices. aGPI prolonged the dRVVT and KCT of beta 2-glycoprotein I (GPI)-depleted normal plasma in the presence of extrinsic GPI. This prolongation of the dRVVT and KCT occurred immediately after the addition of aGPI and GPI, and was subsequently enhanced further in a time dependent manner. The GPI/aGPI combination was judged to have lupus anticoagulant like activity by the dRVVT-platelet neutralization test, but this was not confirmed by a lupus anticoagulant-specific test, i.e., the activated partial prothrombin time (APTT) using hexagonal phospholipid. From these findings, it can be concluded that aGPI has lupus anticoagulant-like activity in the presence of GPI, but may be a partially or considerably different antiphospholipid antibody from lupus anticoagulant. Further investigations may be needed to clarify this point. PMID- 8213769 TI - Hemoglobin sickle-Lepore: report of two siblings and review of the literature. AB - Hemoglobin Lepore is composed of two normal alpha-globin chains and two delta beta fusion globin chains that result from nonhomologous crossing over of genetic material during meiosis. The doubly heterozygous condition of sickle hemoglobin with Lepore hemoglobin (Hb S-Lepore) is rare, having been described previously in only nine patients. We report two siblings with Hb S-Lepore who have similar hematologic characteristics but a marked difference in clinical severity. PMID- 8213770 TI - Coincidental polycythemia vera and multiple myeloma: case report and review. AB - Polycythemia vera (PCV) and multiple myeloma are both clonal disorders of hematopoietic stem cells. The simultaneous occurrence of these diseases in an individual patient is rare. A case of synchronous PCV and smoldering myeloma is presented and the literature is reviewed. The issues of clinical importance in this unusual case include the mechanisms of anemia in multiple myeloma, the difficulty in using anemia as a parameter on which to base the initiation of therapy for myeloma, and the risks of treatment-induced leukemia and myelodysplasia. PMID- 8213771 TI - Macrophage-megakaryocyte interaction in bone marrow after high-dose intravenous immunoglobulin therapy. AB - Localization of IgG in bone marrow after high-dose intravenous immunoglobulin therapy (IVIG) was investigated via light and electron microscopy. IgG was incorporated into the cytoplasm of various types of bone marrow cells of all the three lineages, particularly in reticulum cells, fat cells, and megakaryocytes. In addition, both reticulum cells and fat cells showed many elongated cytoplasmic protrusions, which were in contact with the various types of blood cells, especially the megakaryocytes. A filamentous structure was also seen near the point of contact between the cells. Ultrastructural changes of macrophages in bone marrow after IVIG suggest that these cells were activated by IVIG. PMID- 8213772 TI - Weak N activity of En(a-) human erythrocyte membranes. AB - The propositus's erythrocytes with phenotype En(a-), which was found for the first time in a Japanese family, reacted more weakly with anti-N serum than the ordinary phenotype N erythrocytes. The En(a-) erythrocytes lack the major membrane sialoglycoprotein (glycophorin A) as demonstrated by Bio-Gel 1.5m gel filtration from active sialoglycoproteins, which were isolated from En(a-) erythrocyte membranes by the method of lithium diiodosalicylate (LIS)-phenol extraction. It is suggested from observation via enzyme-linked immunosorbent assay (ELISA) that N activity is derived from the glycophorin B molecule on En(a ) erythrocyte membranes. PMID- 8213773 TI - Human parvovirus B19 infection in bone marrow transplantation patients. AB - We report the results of a survey of parvovirus B19 infection carried out with the aim to evaluate the frequency and the role of this infection in bone marrow transplant (BMT) recipients, as it is known that B19 virus can persist in clinical circumstances of immunodeficiency. Fifty-one patients subjected to BMT in the Bone Marrow Transplantation Center of Florence were enrolled in this study. Immunological and virological indications of B19 infection were tested weekly during the stay in hospital. A high rate of seroconversion or B19 antibody rise was observed, but, in absence of B19 IgM or B19 DNA presence, this result seems to be attributable to a passive immunization, rather than to a recent viral infection. In these 51 patients, as well as in 59 others not included in this study, clinical manifestations imputable to B19 infection have never been observed. It is possible that the isolation measures and the intravenous immunoglobulins (IVIG) administration may contribute in preventing B19 infection in the BMT recipients at least until the hospital discharge. PMID- 8213774 TI - Iron deficiency anemia in hemoglobinopathy. PMID- 8213775 TI - Evaluation of reticulocyte subtype distribution in myelodysplastic syndromes. PMID- 8213776 TI - Availability for absorption of egg yolk-bound cobalt-57-labeled vitamin B12 administered as an omelette or an eggnog. PMID- 8213777 TI - Translocation (11;14)(q13;q32) and partial trisomy 1q in a case of multiple myeloma. PMID- 8213778 TI - Detection of platelet-derived microparticles in patients with diabetes. PMID- 8213779 TI - Cutaneous necrosis caused by injection of alpha-interferon in a patient with chronic myelogenous leukemia. PMID- 8213780 TI - Deleterious effects of intravenous immunoglobulin in a patient with thrombotic thrombocytopenic purpura. PMID- 8213781 TI - Comment on "Study of glucose-6-phosphate dehydrogenase: history and molecular biology," by Ernest Beutler, Am J Hematol 42:53-58, 1993. PMID- 8213782 TI - Late transition of hairy cell leukemia to multiple myeloma. PMID- 8213783 TI - Vesnarinone induced agranulocytosis. PMID- 8213784 TI - Successful treatment of deep vein thrombosis in homozygous protein C deficiency with activated protein C. PMID- 8213785 TI - Blue nasal secretions: a presentation of Gaucher's disease and concurrent hemosiderosis. PMID- 8213786 TI - Does sarcoidosis induce multiple myeloma? PMID- 8213787 TI - Endothelins in the kidney: physiology and pathophysiology. AB - In summary, ET may be important in the pathogenesis of multiple diseases of the kidney. Alterations in ET-1 production and action may lead to severe vasoconstriction, mesangial cell contraction, glomerular cell proliferation, and enhanced sodium and water retention. It is not surprising, therefore, that intense investigations are under way in an effort to develop specific inhibitors of ET action, including ECE inhibitors and ET receptor blockers. It is likely that with the development of these agents, we will uncover even more diseases in which ET mediates renal dysfunction and in which, hopefully, blockers of ET action will be of therapeutic benefit. PMID- 8213788 TI - Autosomal dominant polycystic kidney disease. PMID- 8213789 TI - Renal stone disease in autosomal dominant polycystic kidney disease. AB - Nephrolithiasis is an important manifestation of autosomal dominant polycystic kidney disease (ADPKD), which occurs in approximately 20% of patients. It should always enter the differential diagnosis of flank pain in patients with ADPKD. The diagnosis is hindered by the distorted anatomy of the polycystic kidneys and the frequent occurrence of parenchymal and cyst wall calcifications, and requires demonstration of the relationship to the collecting system by intravenous urography and/or computed tomography. Computed tomography is the most sensitive imaging technique for detection of stones or calcifications, whereas intravenous urography is the most sensitive for visualization of the intrarenal collecting system. Precaliceal tubular ectasia can be detected in 15% of patients with ADPKD and nephrolithiasis, but this association may not be specific to ADPKD. The composition of the stones is most frequently uric acid and/or calcium oxalate. Metabolic factors are important in their pathogenesis. Distal acidification defects may be important in a few patients, while an abnormal transport of ammonium, low urine pH, and hypocitruria are the most common abnormalities. The treatment of nephrolithiasis in patients with ADPKD is not different from that in patients without ADPKD. Extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy in patients with early disease and normal renal function are not contraindicated. PMID- 8213790 TI - Hepatic cysts in autosomal dominant polycystic kidney disease. PMID- 8213791 TI - Intracranial aneurysms in patients with autosomal dominant polycystic kidney disease: how to diagnose and who to screen. PMID- 8213792 TI - Surgical management of painful polycystic kidneys. AB - In patients with symptomatic PKD who have failed medical management, surgical intervention is a reasonable option, providing long-term pain relief in the majority of patients. Individuals for whom this approach is indicated are usually narcotic dependent or disabled by pain. Cyst decompression surgery does not appear to significantly retard or arrest progressive renal insufficiency. On the other hand, widespread fears that cyst decompression might hasten renal failure are clearly unfounded. The application of newer laparoscopic techniques to this problem may allow for a wider range of symptomatic patients to realize the benefits of cyst decompression. PMID- 8213793 TI - Reduced renal hemodynamic response to atrial natriuretic peptide in elderly volunteers. AB - Aging is associated with decreased ability to excrete salt and water, thus increasing the susceptibility to volume overload in older individuals. Meanwhile, plasma levels of atrial natriuretic peptide (ANP) increase progressively with age for unknown reasons. We compared the natriuretic and renal hemodynamic responses to low-dose ANP infusion in an elderly group of volunteers (mean age, 74 years) with those of a group of younger subjects (mean age, 29 years). A significant reduction below baseline values in effective renal plasma flow occurred in the young group after the 2-hour peptide infusion (657 +/- 125 v 476 +/- 92 mL/min [mean +/- 1 SD]) when compared with the elderly group (two-way analysis of variance; P < 0.02). A concomitant increase in renal vascular resistance was noted in the young group only during the same period (6,631 +/- 1,384 v 9,136 +/- 2,126 dyn s cm2 x 10(6)). This increase was also significantly higher than that in the elderly group (analysis of variance; P < 0.02). Both groups demonstrated similar natriuretic responses. Absolute sodium excretion had increased significantly above baseline values in both young and elderly subjects at the end of the 2-hour peptide infusion (111 +/- 25 mumol/min to 183 +/- 33 mumol/min v 107 +/- 23 mumol/min to 198 +/- 56 mumol/min) and remained elevated until 1 hour postinfusion. We conclude that the elderly subjects in our study demonstrated a diminished renal hemodynamic response to infusion of ANP while preserving a natriuretic response similar to that found in the younger subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213794 TI - The use of the automatic core biopsy system in percutaneous renal biopsies: a comparative study. AB - We describe our experience with the use of the automatic core biopsy system for percutaneous renal biopsy and compare this with our experience with a standard biopsy needle. Three hundred twenty-three biopsies were performed between June 1983 and January 1993. From June 1983 through October 1990, 232 biopsies were performed with the use of a standard biopsy needle (Tru-cut needle; Travenol Laboratories, Deerfield, IL) and from November 1990 through January 1993, 91 biopsies were conducted with the use of the automatic core biopsy system (Biopty gun and needle; C.R. Bard, Inc, Covington, GA). Biopsies performed prior to January 1990 were reviewed retrospectively, while those performed after January 1990 were reviewed in a prospective manner. The primary indications for renal biopsy were to evaluate proteinuria (48.9%) and renal manifestations of systemic lupus erythematosus (26.0%). The two groups of patients were similar with respect to sex, age, serum creatinine, and coagulation parameters. Material for light microscopy, immunofluorescence microscopy, and electron microscopy was obtained in 98.9%, 98.9%, and 97.8% of cases, respectively, with the use of the automatic core biopsy system, and these values did not differ significantly from those with the use of the standard needle (99.6%, 96.1%, and 97.8%). Significantly more glomeruli were obtained by light microscopy per biopsy specimen with the use of the automatic core biopsy system versus the standard needle (28 +/- 15 and 21 +/- 13, respectively; P < 0.0001). Complications were assessed and separated by severity. Total complications were observed in 13 patients (14.3%) with the automatic core device and in 31 patients (13.4%) with the standard needle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213795 TI - Identification of the component part in an epoetin alfa preparation that causes pain after subcutaneous injection. AB - The subcutaneous administration of epoetin alfa preparations may cause pain at the injection site. To identify the pain-causing substance in these formulations we performed two double-blind, placebo-controlled, randomized order, cross-over studies. Differences in pain experienced after subcutaneous injection of an epoetin alfa solution and its vehicle were assessed in 36 patients. The vehicle and its component parts, albumin and citrate, were compared in 36 volunteers. Normal saline served as a placebo control in both studies. Pain scores were obtained from visual analogue pain scales with no divisions and from five point verbal descriptive pain scales. Both the epoetin alfa solution and its vehicle caused significantly more pain than normal saline (P < 0.0001) in the patients studied. In volunteers the pain scores with the vehicle or its citrate component were significantly higher (P < 0.0001) when compared with normal saline or with the albumin component of the vehicle. In conclusion, the local pain experienced after subcutaneous administration of epoetin alfa preparations is mainly caused by the citrate component of the buffered solution. Epoetin alfa and the albumin component of the preparation do not play a role in this phenomenon. PMID- 8213797 TI - Multicenter study of hepatitis C virus infection in chronic hemodialysis patients and hemodialysis center staff members. AB - Between April 1990 and December 1991, 499 (65%) of 767 patients and 142 (59%) of 239 staff members from 11 chronic hemodialysis centers in different geographic regions of the United States participated in a multicenter prospective cohort study that determined the prevalence and incidence of antibody to hepatitis C virus (anti-HCV) and evaluated their risk factors for HCV infection. Serum samples were tested for anti-HCV by enzyme immunoassay and HCV neutralization assay at baseline and 9 and 18 months later. Collected data included patient and staff demographics, number of years a patient had been on dialysis or staff were employed in the dialysis field, history and dates of blood transfusions, history of injecting drugs, and history of non-A, non-B hepatitis. Anti-HCV was detected in 52 (10%) of 499 patients and in two (1%) of 142 staff members. Logistic regression analysis revealed that in patients, an anti-HCV-positive test was associated with length of time on dialysis (3 or more years), history of injecting drugs, and history of non-A, non-B hepatitis. Anti-HCV positivity was not associated with history of blood transfusions, race, gender, or age. In patients, the cumulative incidence of HCV infection over an 18-month period was 4.6%. Throughout the 18-month follow-up period, no staff members became anti-HCV positive. The association between anti-HCV positivity and increasing patient years on dialysis may reflect the cumulative risk of exposure to infectious blood in the dialysis environment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213796 TI - Medicare payment policy and recombinant erythropoietin prescribing for dialysis patients. AB - The Medicare payment policy for recombinant human erythropoietin (rHuEPO) treatment for dialysis patients changed in January 1991 from a relatively fixed payment per treatment (allowed charge of $40 per < or = 10,000 units injected) to a more variable payment based on the amount of rHuEPO administered with each treatment (allowed charge of $11 per 1,000 units injected). This change provided an opportunity to examine how payment policy can effect the use, cost, and health outcome of a biotechnology product used in the dialysis population. In cross sectional (n = 71,880 Medicare-entitled dialysis patients) and longitudinal (n = 29,088 Medicare-entitled dialysis patients) study designs, we used Medicare end stage renal disease program and claims data in bivariate and multivariate analyses to examine the effect of the change in payment policy for rHuEPO on access to the biotechnology, dosing, costs, and hematocrit, including the prescribing patterns at for-profit versus not-for-profit providers. The observation period included several months before (July 1989 to December 1990) and 6 months after (January to June 1991) the change in Medicare payment policy. The mean dose per treatment during the initial and fourth month of therapy was low (2,742 [95% confidence interval, 2,703 to 2,781] units and 2,632 [95% confidence interval, 2,598 to 2,667] units, respectively, in June 1990) and increased 3.4% and 5.0%, respectively, in the next 6 months prior to the change in Medicare payment policy compared with 14.6% and 14.8%, respectively, in the 6 months following the change in payment policy. The average monthly allowed charge for rHuEPO per dialysis patient receiving rHuEPO decreased from $455 before the policy change to $349 immediately following the policy change, because the allowed charge per unit of rHuEPO was lower when payment became more dependent on the amount of rHuEPO administered with each treatment than when the payment was fixed at $40 per treatment. The average monthly allowed charge for rHuEPO increased to $375 in the sixth month following the change in payment policy as a result of the increase in dose and the new variable payment. The unadjusted and adjusted changes in mean hematocrit 6 months after the payment change were positive but clinically very small (0.3 and 0.2 percentage points, respectively).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8213798 TI - Detection of hepatitis C infection by polymerase chain reaction among hemodialysis patients. AB - One hundred forty-five patients on regular hemodialysis (HD) at our institution were evaluated for the presence of hepatitis C virus (HCV) infection. Forty-three patients (29%) were found to have detectable antibodies to HCV using second generation enzyme-linked immunosorbent and recombinant immunoblot assays. Forty positive patients (anti-HCV+) and 10 negative patients (anti-HCV-) were tested for direct detection of the HCV genome by the polymerase chain reaction (PCR). Twenty-one anti-HCV+ patients (52%) had detectable RNA HCV in plasma (PCR+). No anti-HCV- patient had viremia. In addition, we compared the 43 anti-HCV+ patients with the 102 anti-HCV- patients for duration of HD, history of blood transfusion, serologic markers of hepatitis B virus, and acute and chronic liver disease. On retrospective univariate analysis, statistically significant associations with anti-HCV+ were duration of HD (P = 0.0001), blood transfusions (P = 0.0005), co infection with hepatitis B virus (P = 0.01), and acute and chronic liver disease (P = 0.06 and 0.01, respectively). Three significant variables (duration of HD, chronic hepatitis, and blood transfusions) of the multivariate analysis permit the classification of 65% of anti-HCV+ patients and 81% of anti-HCV- patients. In the anti-HCV+ group, when the same parameters were compared in PCR+ or PCR- patients, no statistical difference appeared. These results reveal that 52% of anti-HCV+ HD patients have HCV infection. The clinical consequences of HCV infection in that population are not characterized since no difference has been documented between PCR+ and PCR- results. PMID- 8213799 TI - Nontuberculous mycobacterial infections in continuous ambulatory peritoneal dialysis patients. AB - Nontuberculous mycobacterial infections are a rare but clinically important cause of infections in continuous ambulatory peritoneal dialysis (CAPD) patients. We describe seven cases of catheter-related nontuberculous mycobacterial infections associated with CAPD. Six patients had Mycobacterium fortuitum infections and one had a Mycobacterium kansasii infection. Three patients presented with peritonitis, three presented with exit site infections, and one developed an infection at the exit site after catheter removal. There were no specific clinical findings that differentiated these infections from those caused by common bacterial pathogens. Initial routine peritoneal dialysis fluid and exit site cultures were negative in two patients and grew M fortuitum in four patients and M kansasii in one patient. M fortuitum and M kansasii were sensitive to amikacin, and M fortuitum was sensitive to ciprofloxacin when tested. Sensitivities to other antibiotics were variable. All patients were treated with a combination of antibiotics from 3 weeks to 6 months. Catheter removal was necessary for cure of the infection in all patients with peritonitis and in a majority of patients with exit site infections. The majority of patients changed to hemodialysis after catheter removal. Two patients remained on CAPD, with follow-up ranging from 2 months to 4 years. One patient has received a successful renal transplant. In conclusion, M fortuitum is the most common nontuberculous mycobacterial catheter-related infection in CAPD patients. Nontuberculous mycobacterial infections should be considered in the differential diagnosis of any culture-negative infection associated with CAPD. In patients with infections secondary to M fortuitum, our findings suggest that amikacin and ciprofloxacin are the initial antibiotics of choice until antibiotic sensitivities are available. PMID- 8213800 TI - Advanced glycosylation end products in continuous ambulatory peritoneal dialysis patients. AB - Low molecular weight advanced glycosylation end products (AGEs) were evaluated for by an enzyme-linked immunosorbent assay in 30 patients on continuous ambulatory peritoneal dialysis (29 patients) and continuous cyclic peritoneal dialysis (one patient). Thirteen patients were diabetic and 17 patients were nondiabetic. All patients underwent peritoneal equilibration tests and, in addition to routine chemistries, serum and dialysate were evaluated for AGEs. Serum creatinine levels were similar in the diabetic and nondiabetic patients, but serum AGE levels were significantly higher in the diabetic patients (16.2 +/- 5.3 v 8.2 +/- 2.3 U/mL; P < 0.0001). Overall, the dialysate to plasma ratio at 4 hours was 0.69 +/- 0.08 for creatinine and 0.18 +/- 0.06 for AGEs. The mass transfer area coefficient for all patients was 12.4 +/- 3.12 mL/min for creatinine and 2.03 +/- 0.93 mL/min for AGEs. The peritoneal transport of AGEs as measured by dialysate to plasma ratios at 4 hours and by mass transfer area coefficients was significantly less (P < 0.001) than that for creatinine. No significant difference in dialysate to plasma ratios or mass transfer area coefficient for creatinine or AGEs was noted between diabetic and nondiabetic patients. The peritoneal transport of AGEs is poor and leads to elevated serum levels, especially in patients with diabetes mellitus. The accumulation of AGEs may contribute to the increased cardiovascular mortality seen in patients with end stage renal disease. This is most marked in patients with diabetes mellitus. PMID- 8213801 TI - Ablation of irreversibly rejected renal allograft by embolization with absolute ethanol: a new clinical application. AB - Surgical allograft nephrectomy has been the conventional therapy for removing failed kidney allografts when clinical manifestations of graft intolerance appear. However, removal of a transplanted kidney is an extensive surgical procedure. On the other hand, transcatheter vascular embolization (TVE) has proven useful in ablating organs and could be applied to renal transplant ablation. The aim of this study was to present the results of TVE for the treatment of graft intolerance syndrome (GIS) in failed allograft kidneys. Transcatheter vascular embolization was performed in 14 allograft recipients (33 +/- 13 years of age; 10 men and four women) affected by GIS after irreversible kidney allograft failure. Graft intolerance syndrome was diagnosed by fever (93%), hematuria (50%), graft pain (36%), flu-like symptoms (29%), and increased graft size (29%). Absolute ethanol (0.1 mL/kg body weight) was injected in the allograft artery, and in seven patients a stainless steel coil was left in the renal artery following ethanol injection. All patients showed clinical disappearance of the GIS. No major complication occurred, although a postembolization syndrome of pain, fever, hematuria, numbness, and paresthesia of the affected area appeared in 11 of the 14 patients. After 2 to 56 months of follow-up no late complications occurred, with the exception of a graft abscess formation in one patient after 6 months of embolization. Subsequent transplantectomy was uneventful. In conclusion, TVE is a safe and effective method for kidney graft ablation, and it may become an alternative treatment for GIS following irreversible rejection. PMID- 8213802 TI - Health care payment policies: lessons from erythropoietin. PMID- 8213803 TI - Ciprofloxacin-induced granulomatous interstitial nephritis and localized elastolysis. AB - Ciprofloxacin is known to cause acute interstitial nephritis. We report the first case of ciprofloxacin-induced granulomatous interstitial nephritis and localized elastolysis. The patient presented with acute renal failure and skin lesions following a 14-day course of ciprofloxacin administered for cellulitis. The patient had symmetric, palm-sized, tender violaceous plaques on both axillae. The renal biopsy revealed granulomatous interstitial disease. A skin biopsy revealed an elastolytic process with histocytic infiltration and calcification. After discontinuing ciprofloxacin and starting a short course of steroid therapy, the skin lesion and renal function improved promptly. The nephritis relapsed after prednisone was discontinued and responded to a second course of steroid therapy. Ciprofloxacin, like penicillin, can cause granulomatous interstitial nephritis and elastolysis. A prolonged course of steroid therapy may be indicated in patients with ciprofloxacin-induced granulomatous interstitial nephritis to avoid early relapse. PMID- 8213804 TI - Hyperkalemia with high-dose trimethoprim-sulfamethoxazole therapy. AB - In a patient with the acquired immunodeficiency syndrome, a progressive increase in the serum potassium concentration occurred with high-dose trimethoprim sulfamethoxazole (TMP-SMX) therapy for Pneumocystis carinii pneumonia. In this patient, factors known to alter transcellular potassium shifts to induce hyperkalemia were not present. There was no evidence of glucocorticoid or mineralocorticoid insufficiency at the time of hyperkalemia, while the transtubular potassium gradient decreased. The hyperkalemia resolved spontaneously on discontinuation of TMP-SMX therapy, suggesting that this electrolyte abnormality is related to altered renal tubular secretion of potassium as a consequence of the high-dose TMP-SMX therapy. PMID- 8213805 TI - Macroscopic hematuria as a presenting manifestation of oliguric acute tubular necrosis. AB - Macroscopic hematuria associated with acute renal failure usually results from glomerulonephritis or structural abnormalities (stones, tumors, or infections). Acute tubular necrosis is rarely associated with macroscopic hematuria in the absence of other genitourinary abnormalities. We describe a patient who presented with macroscopic hematuria, in whom only acute tubular necrosis could be identified as a causative factor. PMID- 8213806 TI - Rapidly progressive acute renal failure due to acyclovir: case report and review of the literature. AB - Acyclovir nephrotoxicity has been described since the inception of the drug's use more than a decade ago. Acute renal failure mediated by this compound is characterized by abrupt elevations in serum creatinine and a gradual return to baseline renal function on discontinuation of the drug. Drug crystal formation in collecting tubules resulting in an intraparenchymal form of obstructive nephropathy has been suggested as the mechanism for acyclovir nephrotoxicity. The patient we present developed rapidly progressive acute renal failure with concomitant mental status changes in the setting of treatment with high-dose parenteral acyclovir. Acyclovir therapy was discontinued and an open renal biopsy was obtained to further evaluate our patient's diminishing renal function. Pathologic examination of the biopsy specimen revealed loss of proximal tubule brush border and dilated proximal and distal tubules with flattening of lining cells and focal nuclear loss. No crystals were noted. These changes were consistent with acute tubular necrosis with regeneration. Over the next 4 days our patient's renal and neurologic levels recovered to their prehospitalization statuses. It appears that our patient was affected by acyclovir-mediated nephrotoxicity that manifested on biopsy by acute tubular necrosis and the absence of crystalluria or crystal deposition. Intravenous acyclovir treatment can therefore produce rapidly progressive acute neurologic and renal toxicity that is usually reversible. The pathologic changes of acute tubular necrosis must now be included as part of the spectrum of renal damage associated with acyclovir therapy. PMID- 8213807 TI - The measurement of dialysis access recirculation. AB - The measurement of dialysis access recirculation has important diagnostic implications. Recent recognition that its traditional means of measurement is fraught with the potential for substantially overestimating access recirculation requires that we alter current practice. Most of the potential error in the measurement can be overcome by using an arterial rather than a venous specimen for the "systemic" sample. For practical purposes, such a sample can be drawn from the dialysis afferent (arterial) line as long as it is done in a manner that minimizes both contamination by recirculated blood as well as the increase in blood urea nitrogen that occurs when the arteriovenous blood urea nitrogen gradient is dissipated by slowing or stopping dialysis. PMID- 8213808 TI - Heparin and urokinase in situ for partial thrombosis of indwelling hemodialysis catheters. PMID- 8213809 TI - Improved diuretic response with immunosuppressive therapy. PMID- 8213810 TI - Evidence that methylation of the FMR-I locus is responsible for variable phenotypic expression of the fragile X syndrome. AB - DNA at the FMR-1 locus was analyzed by Southern blot using probe StB12.3 in an unusual fragile X family with six brothers, three of whom are affected with fragile X to varying degrees, two of whom are nonpenetrant carriers, and one of whom is unaffected. Fragile X chromosome studies, detailed physical examinations, and psychological testing were completed on all six. Two of the affected brothers and the two nonpenetrant brothers were found to be methylation mosaics. The three affected males spanned the phenotypic and cognitive spectrum of the fragile X syndrome. A correlation was seen between the degree of methylation and the phenotypic expression identified in the three affected males. The two males initially classified as nonpenetrant were found to have mild phenotypic expression which consisted of minor cognitive deficits and a partial physical phenotype. These two, who were negative on fragile X chromosome studies, were found on DNA analysis to have large broad smears, with approximately 97% of the DNA unmethylated. The results described here indicate that some "nonpenetrant" carrier males may have varying amounts of methylation of the FMR-1 region, which can result in mild expression of the fragile X syndrome. The apparently mild phenotypic and cognitive expression of the fragile X syndrome in the two males, initially classified as nonpenetrant, who are mosaic for hypermethylation of an expansion of the CGG repeat in the premutation range, indicates that expression of the syndrome is not confined to males with large, hypermethylated expansions (full mutation) but has instead a gradient effect with a threshold for the full expression of the phenotype. PMID- 8213811 TI - Overexpression of esterase D in kidney from trisomy 13 fetuses. AB - Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses and has been compared with normal age- and sex matched fetal tissues, by using northern analysis. More than a twofold increase in expression of esterase D was found in the kidney of two trisomy 13 fetuses, with normal levels in a third. Overexpression was not seen in the muscle tissues from these fetuses. PMID- 8213812 TI - A new nucleotide-excision-repair gene associated with the disorder trichothiodystrophy. AB - The sun-sensitive, cancer-prone genetic disorder xeroderma pigmentosum (XP) is associated in most cases with a defect in the ability to carry out excision repair of UV damage. Seven genetically distinct complementation groups (i.e., A G) have been identified. A large proportion of patients with the unrelated disorder trichothiodystrophy (TTD), which is characterized by hair-shaft abnormalities, as well as by physical and mental retardation, are also deficient in excision repair of UV damage. In most of these cases the repair deficiency is in the same complementation group as is XP group D. We report here on cells from a patient, TTD1BR, in which the repair defect complements all known XP groups (including XP-D). Furthermore, microinjection of various cloned human repair genes fails to correct the repair defect in this cell strain. The defect in TTD1BR cells is therefore in a new gene involved in excision repair in human cells. The finding of a second DNA repair gene that is associated with the clinical features of TTD argues strongly for an involvement of repair proteins in hair-shaft development. PMID- 8213813 TI - Sequence variation in the androgen receptor gene is not a common determinant of male sexual orientation. AB - To test the hypothesis that DNA sequence variation in the androgen receptor gene plays a causal role in the development of male sexual orientation, we have (1) measured the degree of concordance of androgen receptor alleles in 36 pairs of homosexual brothers, (2) compared the lengths of polyglutamine and polyglycine tracts in the amino-terminal domain of the androgen receptor in a sample of 197 homosexual males and 213 unselected subjects, and (3) screened the the entire androgen receptor coding region for sequence variation by PCR and denaturing gradient-gel electrophoresis (DGGE) and/or single-strand conformation polymorphism analysis in 20 homosexual males with homosexual or bisexual brothers and one homosexual male with no homosexual brothers, and screened the amino terminal domain of the receptor for sequence variation in an additional 44 homosexual males, 37 of whom had one or more first- or second-degree male relatives who were either homosexual or bisexual. These analyses show that (1) homosexual brothers are as likely to be discordant as concordant for androgen receptor alleles; (2) there are no large-scale differences between the distributions of polyglycine or polyglutamine tract lengths in the homosexual and control groups; and (3) coding region sequence variation is not commonly found within the androgen receptor gene of homosexual men. The DGGE screen identified two rare amino acid substitutions, ser205-to-arg and glu793-to-asp, the biological significance of which is unknown. PMID- 8213814 TI - Polymorphic microsatellites and Wilson disease (WD). AB - Wilson disease (WD), an autosomal recessive disorder of copper metabolism, has been previously mapped to chromosome 13q. Highly informative PCR-based polymorphic microsatellites closely linked to the WD locus (WND) at 13q14.3, as well as sequence-tagged sites for closely linked loci, are described. Two polymorphic microsatellite markers at D13S118 and D13S119 lie within 3 cM of WND. Two others (D13S227 and D13S228) were derived from a yeast artificial chromosome containing D13S31. These were placed on a genetic linkage map of chromosome 13 and were typed in 74 multiplex WD families from a variety of geographic origins (166 affected members). Multipoint analysis provides very high odds that the location of WND is between D13S31/D13S227/D13S228 and D13S59. Previous odds with RFLP-based markers were only 7:1 more likely than any other location. Current odds are 5,000:1. Preclinical testing of three cases of WD by using the highly informative polymorphic microsatellite markers is described. The markers described here ensure that 95% of predictive tests using DNA from both parents and from at least one affected sib will have an accuracy > 99%. PMID- 8213815 TI - A radiation hybrid map of 15 loci on the distal long arm of chromosome 4, the region containing the gene responsible for facioscapulohumeral muscular dystrophy (FSHD). AB - A physical map of 4q35 was constructed through radiation hybrid analysis of 134 clones generated from the cell line HHW416, a chromosome 4-only human-hamster somatic cell hybrid. This subtelomeric region contains the as-yet-unidentified gene responsible for facioscapulohumeral muscular dystrophy. The most likely order of 15 loci within 4q35 was determined. The loci ordered on this radiation hybrid map include both genes and polymorphic loci, as well as monomorphic loci which cannot be placed on a genetic linkage map. The physical distance spanning these loci was estimated to be approximately 4.5 Mb, by using a kilobase/centiray conversion factor derived from 4p16.3 marker analysis through the same set of radiation hybrids. The comparison of this physical map to establish genetic maps suggests that this region is smaller than initially estimated and that recombination rates are increased near the telomere. PMID- 8213816 TI - Mutations in acid beta-galactosidase cause GM1-gangliosidosis in American patients. AB - We describe four new mutations in the beta-galactosidase gene. These are the first mutations causing infantile and juvenile GM1-gangliosidosis to be described in American patients. Cell lines from two patients with juvenile and from six patients with infantile GM1-gangliosidosis were analyzed. Northern blot analysis showed the acid beta-galactosidase message to be of normal size and quantity in two juvenile and four infantile cases and of normal size but reduced quantity in two infantile cases. The mutations are distinct from the Japanese mutations. All are point mutations leading to amino acid substitutions: Lys577-->Arg, Arg590- >His, and Glu632-->Gly. The fourth mutation, Arg208-->Cys, accounts for 10 of 16 possible alleles. Two infantile cases from Puerto Rico of Spanish ancestry are homozygous for this mutation, suggesting that this allele may have come to South America and North America via Puerto Rico. That these mutations cause clinical disease was confirmed by marked reduction in catalytic activity of the mutant proteins in the Cos-1 cell expression system. PMID- 8213818 TI - An autologistic model for the genetic analysis of familial binary data. AB - Regressive logistic models specify the probability distribution of familial binary traits by conditioning each individual's phenotype on those of preceding relatives; therefore, the expression of the joint probability of the familial data necessitates ordering the observations. In the present paper, we propose an autologistic model of this familial dependence structure, which does not require specification of a particular ordering of the phenotypic observations. Genetic effects are introduced into the model in order to perform segregation analysis that is aimed at detecting the role of a major locus in the expression of familial phenotypes. In this model, the conditional probabilities have a logistic form, and large patterns of dependence between relatives can be considered with a simple interpretation of the parameters measuring the relationship between two phenotypes. The model is compared with the regressive logistic approach in terms of odds ratios and by using a simulation study. PMID- 8213817 TI - Hereditary overexpression of adenosine deaminase in erythrocytes: evidence for a cis-acting mutation. AB - Overexpression of adenosine deaminase (ADA) in red blood cells is inherited as an autosomal dominant trait and causes hemolytic anemia. The increased ADA activity in erythrocytes is due to an increase in steady-state levels of ADA mRNA of normal sequence. Increased ADA mRNA may be due to a cis-acting mutation which results in increased transcription or a loss of down-regulation during erythroid differentiation. Alternatively, it is possible that the mutation is in a trans acting factor which interacts with normal ADA transcriptional elements to cause overexpression in red blood cells. To discriminate between a cis-acting and a trans-acting mutation, we took advantage of a highly polymorphic TAAA repeat located at the tail end of an Alu repeat approximately 1.1 kb upstream of the ADA gene. Using PCR to amplify this region, we identified five different alleles in 19 members of the family. All 11 affected individuals had an ADA allele with 12 TAAA repeats, whereas none of the 8 normal individuals did. We conclude that this disorder results from a cis-acting mutation in the vicinity of the ADA gene. PMID- 8213819 TI - Two-locus models of disease: comparison of likelihood and nonparametric linkage methods. AB - The power to detect linkage for likelihood and nonparametric (Haseman-Elston, affected-sib-pair, and affected-pedigree-member) methods is compared for the case of a common, dichotomous trait resulting from the segregation of two loci. Pedigree data for several two-locus epistatic and heterogeneity models have been simulated, with one of the loci linked to a marker locus. Replicate samples of 20 three-generation pedigrees (16 individuals/pedigree) were simulated and then ascertained for having at least 6 affected individuals. The power of linkage detection calculated under the correct two-locus model is only slightly higher than that under a single locus model with reduced penetrance. As expected, the nonparametric linkage methods have somewhat lower power than does the lod-score method, the difference depending on the mode of transmission of the linked locus. Thus, for many pedigree linkage studies, the lod-score method will have the best power. However, this conclusion depends on how many times the lod score will be calculated for a given marker. The Haseman-Elston method would likely be preferable to calculating lod scores under a large number of genetic models (i.e., varying both the mode of transmission and the penetrances), since such an analysis requires an increase in the critical value of the lod criterion. The power of the affected-pedigree-member method is lower than the other methods, which can be shown to be largely due to the fact that marker genotypes for unaffected individuals are not used. PMID- 8213820 TI - Pitfalls in the molecular genetic diagnosis of Leber hereditary optic neuropathy (LHON). AB - Pathogenetic mutations in mtDNA are found in the majority of patients with Leber hereditary optic neuropathy (LHON), and molecular genetic techniques to detect them are important for the diagnosis. A false-positive molecular genetic error has adverse consequences for the diagnosis of this maternally inherited disease. We found a number of mtDNA polymorphisms that occur adjacent to known LHON associated mutations and that confound their molecular genetic detection. These transition mutations occur at mtDNA nt 11779 (SfaNI site loss, 11778 mutation), nt 3459 (BsaHI site loss, 3460 mutation), nt 15258 (AccI site loss, 15257 mutation), nt 14485 (mismatch primer Sau3AI site loss, 14484 mutation), and nt 13707 (BstNI site loss, 13708 mutation). Molecular genetic detection of the most common pathogenetic mtDNA mutations in LHON, using a single restriction enzyme, may be confounded by adjacent polymorphisms that occur with a false-positive rate of 2%-7%. PMID- 8213821 TI - Prevalence of nine mutations among Jewish and non-Jewish Gaucher disease patients. AB - The frequency of nine different mutated alleles known to occur in the glucocerebrosidase gene was determined in 247 Gaucher patients, of whom 176 were of Jewish extraction, 2 were Jewish with one converted parent, and 69 were of non Jewish origin. DNA was prepared from peripheral blood, active glucocerebrosidase sequences were amplified by using the PCR technique, and the mutations were identified by using the allele-specific oligonucleotide hybridization method. The N37OS mutation appeared in 69.77% of the mutated alleles in Jewish patients and in 22.86% of the mutated alleles in non-Jews. The 84GG mutation, which has not been found so far among non-Jewish patients, existed in 10.17% of the disease alleles among Jewish patients. The IVS + 1 mutation constituted 2.26% of the disease alleles among Jewish patients and 1.43% among the non-Jewish patients. RecTL, a complex allele containing four single-base-pair changes, occurred in 2.26% of the alleles in Jewish patients and was found in two (1.43%) of the patients of non-Jewish extraction. Another complex allele, designated "RecNciI" and containing three single-point mutations, appeared in 7.8% of alleles of non Jewish patients and in only two (0.56%) of the Jewish families. The prevalence of the L444P mutation among non-Jewish Gaucher patients was 31.43%, while its prevalence among Jewish patients was only 4.24%. The prevalence of two other point mutations--D409H and R463C--was 5.00% and 3.57%, respectively, among non Jewish patients and was not found among the Jewish Gaucher patient population. The prevalence of the R496H mutation, found so far only among Jewish patients, was 1.13%. The results presented demonstrate that seven mutations identify 90.40% of the mutations among Jewish patients and that these seven mutations allow diagnosis of only 73.52% of the non-Jewish patients. Identification of additional mutant alleles will enhance the accuracy of carrier detection. PMID- 8213822 TI - Genetic heterogeneity in neuronal ceroid lipofuscinosis (NCL): evidence that the late-infantile subtype (Jansky-Bielschowsky disease; CLN2) is not an allelic form of the juvenile or infantile subtypes. AB - The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurons and other cell types. Inheritance is autosomal recessive. Three main childhood subtypes are recognized: infantile (Haltia-Santavuori disease; MIM 256743), late infantile (Jansky-Bielschowsky disease; MIM 204500), and juvenile (Spielmeyer-Sjogren-Vogt, or Batten, disease; MIM 204200). The gene loci for the juvenile (CLN3) and infantile (CLN1) types have been mapped to human chromosomes 16p and 1p, respectively, by linkage analysis. Linkage analysis of 25 families segregating for late-infantile NCL has excluded these regions as the site of this disease locus (CLN2). The three childhood subtypes of NCL therefore arise from mutations at distinct loci. PMID- 8213823 TI - Confirmation of chromosome 9p linkage in familial melanoma. AB - Malignant melanoma occurs as a familial cancer in 5%-10% of cases where it segregates in a manner consistent with autosomal dominant inheritance. Evidence from cytogenetics, fine-mapping studies of deletions in melanomas, and recent linkage studies supports the location of a human melanoma predisposition gene on the short arm of chromosome 9. We have carried out linkage analysis using the 9p markers IFNA and D9S126 in 26 Australian melanoma kindreds. Multipoint analysis gave a peak lod score of 4.43, 15 cM centromeric to D9S126, although a lod score of 4.13 was also found 15 cM telomeric of IFNA. These data confirm the existence of a melanoma susceptibility gene on 9p and indicate that this locus most probably lies outside of the IFNA-D9S126 interval. No significant heterogeneity was found between families, when either pairwise or multipoint data were analyzed using HOMOG. PMID- 8213824 TI - HLA polymorphism in the Havasupai: evidence for balancing selection. AB - The characterization and analysis of genetic variation at the HLA loci provides important insight for population geneticists trying to understand the evolutionary forces that have shaped human populations. This study describes the HLA-A and HLA-B loci serotyping and statistical analysis on an isolated Native American population, the Havasupai of Arizona. Four alleles at the HLA-A locus were identified, while eight alleles were found at the HLA-B locus. These variants were present as 20 of 32 potential two-locus haplotypes, with five of the six most common haplotypes exhibiting high positive linkage disequilibrium. Significant homozygote deficiency (heterozygosity excess) was detected both at HLA-A and at HLA-B. This deviation from Hardy-Weinberg proportions was not attributable to nonselective causes such as different allele frequencies in males and females or avoidance of consanguineous matings. In addition, the distribution of alleles at both HLA-A and HLA-B was more even than expected from neutrality theory; that is, the observed Hardy-Weinberg homozygosity was only 62.4% of that expected under neutrality. These observations suggest that balancing selection is of major importance in maintaining genetic variation at HLA-A and HLA-B. PMID- 8213826 TI - Further concerns about the genetics of pre-eclampsia. PMID- 8213825 TI - When does bilateral optic atrophy become Leber hereditary optic neuropathy? PMID- 8213827 TI - An A-to-G transition at nucleotide pair 11084 in the ND4 gene may be an mtDNA polymorphism. PMID- 8213828 TI - Exon skipping and translation in patients with frameshift deletions in the dystrophin gene. AB - Although many Duchenne muscular dystrophy patients have a deletion in the dystrophin gene which disrupts the translational reading frame, they express dystrophin in a small proportion of skeletal muscle fibers ("revertant fibers"). Antibody studies have shown, indirectly, that dystrophin synthesis in revertant fibers is facilitated by a frame-restoring mechanism; in the present study, the feasibility of mRNA splicing was investigated. Dystrophin transcripts were analyzed in skeletal muscle from individuals possessing revertant fibers and a frameshift deletion in the dystrophin gene. In each case a minor in-frame transcript was detected, in which exons adjacent to those deleted from the genome had been skipped. There appeared to be some correlation between the levels of in frame transcripts and the predicted translation products. Low levels of alternatively spliced transcripts were also present in normal muscle. The results provide further evidence of exon skipping in the dystrophin gene and indicate that this may be involved in the synthesis of dystrophin by revertant fibers. PMID- 8213829 TI - Influence of sex of the transmitting parent as well as of parental allele size on the CTG expansion in myotonic dystrophy (DM). AB - In patients with myotonic dystrophy (DM), the severity of clinical signs is correlated with the length of a (CTG)n trinucleotide repeat sequence. This sequence tends to expand in subsequent generations. In order to examine the kinetics of this process and, in particular, the influence of the mutant-allele size and the sex of the transmitting parent, we have studied (CTG)n repeat lengths in the offspring of 38 healthy carriers with small mutations (less than 100 CTG trinucleotides, mean length [CTG]67). In these studies, we found a weakly positive correlation between the size of the mutation in the carrier parents and that in their offspring. Furthermore, we observed that, in the offspring of male transmitters, repeat lengths exceeding 100 CTG trinucleotides were much more frequent than in the offspring of carrier females (48 [92%] of 52 vs. 7 [44%] of 16, P = .0002). Similarly, in genealogical studies performed in 38 Dutch DM kindreds, an excess of nonmanifesting male transmitters was noted, which was most conspicuous in the generation immediately preceding that with phenotypic expression of DM. Thus, two separate lines of evidence suggest that the sex of the transmitting parent is an important factor that determines DM allele size in the offspring. On the basis of our data, we estimate that when both parents are asymptomatic, the odds are approximately 2:1 that the father carries the DM mutation. Because expansion of the CTG repeat is more rapid with male transmission, negative selection during spermatogenesis may be required to explain the exclusive maternal inheritance of severe congenital onset DM. PMID- 8213830 TI - Exclusion of the APC gene as the cause of a variant form of familial adenomatous polyposis (FAP) AB - Familial adenomatous polyposis (FAP) is a premalignant disease inherited as an autosomal dominant trait, characterized by hundreds to thousands of polyps in the colorectal tract. Recently, the syndrome has been shown to be caused by mutations in the APC (adenomatous polyposis coli) gene located on chromosome 5q21. We studied two families that both presented a phenotype different than that of the classical form of FAP. The most important findings observed in these two kindreds are (a) low and variable number of colonic polyps (from 5 to 100) and (b) a slower evolution of the disease, with colon cancer occurring at a more advanced age than in FAP in spite of the early onset of intestinal manifestations. To determine whether mutations of the APC gene are also responsible for this variant syndrome, linkage studies were performed by using a series of markers both intragenic and tightly linked to the APC gene. The results provide evidence for exclusion of the APC gene as the cause of the variant form of polyposis present in the two families described. PMID- 8213831 TI - A single-gene explanation for the probability of having idiopathic talipes equinovarus. AB - It has been hypothesized that the pathogenesis of idiopathic talipes equinovarus (ITEV, or clubfoot) is explained by genetic regulation of development and growth. The objective of the present study was to determine whether a single Mendelian gene explains the probability of having ITEV in a sample of 143 Caucasian pedigrees from Iowa. These pedigrees were ascertained through probands with ITEV. Complex segregation analyses were undertaken using a regressive logistic model. The results of these analyses strongly rejected the hypotheses that the probability of having ITEV in these pedigrees was explained by a non-Mendelian pattern of transmission with residual sibling correlation, a nontransmitted (environmental) factor with residual sibling correlation, or residual sibling correlation alone. These results were consistent with the hypothesis that the probability of having ITEV was explained by the Mendelian segregation of a single gene with two alleles plus the effects of some unmeasured factor(s) shared among siblings. The segregation of alleles at this single Mendelian gene indicated that the disease allele A was incompletely dominant to the nondisease allele B. The disease allele A, associated with ITEV affection, was estimated to occur in the population of inference with a frequency of .007. After adjusting for sex specific population incidences of ITEV, the conditional probability (penetrance) of ITEV affection given the AA, AB, and BB genotypes was computed to be 1.0, .039, and .0006, respectively. Individual pedigrees in this sample that most strongly supported the single Mendelian gene hypothesis were identified. These pedigrees are candidates for genetic linkage analyses or DNA association studies. PMID- 8213832 TI - Genotype-phenotype relationships in fragile X syndrome: a family study. AB - Relationships between the measures of intellectual and physical status in the fragile X syndrome and the size of amplification of the fragile X-specific fragment, equivalent to the number of CCG repeats within the FMR1 locus, were studied by a maximum-likelihood scoring technique for analysis of pedigree data. This allows for estimation of random effects (genetic and environmental variance) concurrently with other (fixed) effects in a quantitative trait. FMR1 expression is usually shut down in males penetrant for the fragile X syndrome who have hypermethylated CCG amplifications of > or = 0.6 kb. The assumption of the step versus curvilinear function representing this relationship was tested by the likelihood-ratio criterion. The maximum-likelihood parameters were based on the most appropriate model for each measure. The results were indicative of the presence of a curvilinear relationship between the amplification size and the two intellectual scores, the Peabody Picture Vocabulary Test and Block Design Test, measuring verbal and spatial abilities, respectively. Reasons for the unexpected curvilinear regression between the amplification size and intellectual scores were explained further by methylation analysis of fragile X males with amplifications of 0.6 < delta < or = 1.2 kb who appeared to be responsible for the curvilinearity of the relationship. Four of these showed unmethylated status of the amplified bands in lymphocytes, which were presumably transcriptionally active. Removal of the aberrant individuals led to the anticipated step function between amplification and intellectual scores. For the combined anthropometric score, as well as for several single physical measures, the step function was the most appropriate model regardless of the inclusion or omission of the aberrant individuals in the pedigree sample. PMID- 8213833 TI - Normal phenotype with paternal uniparental isodisomy for chromosome 21. AB - Uniparental disomy (UPD) involving several different chromosomes has been described in several cases of human pathologies. In order to investigate whether UPD for chromosome 21 is associated with abnormal phenotypes, we analyzed DNA polymorphisms in DNA from a family with de novo Robertsonian translocation t(21q;21q). The proband was a healthy male with 45 dup(21q) who was ascertained through his trisomy 21 offspring. No phenotypic abnormalities were noted in the physical exam, and his past medical history was unremarkable. We obtained genotypes for the proband and his parents' leukocyte DNAs from 17 highly informative short sequence repeat polymorphisms that map in the pericentromeric region and along the entire length of 21q. The order of the markers has been previously determined through the linkage and physical maps of this chromosome. For the nine informative markers there was no maternal allele contribution to the genotype of the proband; in addition, there was always reduction to homozygosity of a paternal allele. These data indicated that there was paternal uniparental isodisomy for chromosome 21 (pUPiD21). We conclude that pUPiD21 is not associated with abnormal phenotypes and that there are probably no imprinted genes on chromosome 21. PMID- 8213834 TI - Evidence for human meiotic recombination interference obtained through construction of a short tandem repeat-polymorphism linkage map of chromosome 19. AB - An improved linkage map for human chromosome 19 containing 35 short tandem repeat polymorphisms (STRPs) and one VNTR (D19S20) was constructed. The map included 12 new (GATA)n tetranucleotide STRPs. Although total lengths of the male (114 cM) and female (128 cM) maps were similar, at both ends of the chromosome male recombination exceeded female recombination, while in the interior portion of the map female recombination was in excess. Cosmid clones containing the STRP sequences were identified and were positioned along the chromosome by fluorescent in situ hybridization. Four rounds of careful checking and removal of genotyping errors allowed biologically relevant conclusions to be made concerning the numbers and distributions of recombination events on chromosome 19. The average numbers of recombinations per chromosome matched closely the lengths of the genetic maps computed by using the program CRIMAP. Significant numbers of chromosomes with zero, one, two, or three recombinations were detected as products of both female and male meioses. On the basis of the total number of observed pairs of recombination events in which only a single informative marker was situated between the two recombinations, a maximal estimate for the rate of meiotic STRP "gene" conversion without recombination was calculated as 3 x 10( 4)/meiosis. For distances up to 30 cM between recombinations, many fewer chromosomes which had undergone exactly two recombinations were observed than were expected on the basis of the assumption of independent recombination locations. This strong new evidence for human meiotic interference will help to improve the accuracy of interpretation of clinical DNA test results involving polymorphisms flanking a genetic abnormality. PMID- 8213835 TI - Genotype relative risks: methods for design and analysis of candidate-gene association studies. AB - Design and analysis methods are presented for studying the association of a candidate gene with a disease by using parental data in place of nonrelated controls. This alternative design eliminates spurious differences in allele frequencies between cases and nonrelated controls resulting from different ethnic origins and population stratification for these two groups. We present analysis methods which are based on two genetic relative risks: (1) the relative risk of disease for homozygotes with two copies of the candidate gene versus homozygotes without the candidate gene and (2) the relative risk for heterozygotes with one copy of the candidate gene versus homozygotes without the candidate gene. In addition to estimating the magnitude of these relative risks, likelihood methods allow specific hypotheses to be tested, namely, a test for overall association of the candidate gene with disease, as well as specific genetic hypotheses, such as dominant or recessive inheritance. Two likelihood methods are presented: (1) a likelihood method appropriate when Hardy-Weinberg equilibrium holds and (2) a likelihood method in which we condition on parental genotype data when Hardy Weinberg equilibrium does not hold. The results for the relative efficiency of these two methods suggest that the conditional approach may at times be preferable, even when equilibrium holds. Sample-size and power calculations are presented for a multitiered design. The purpose of tier 1 is to detect the presence of an abnormal sequence for a postulated candidate gene among a small group of cases. The purpose of tier 2 is to test for association of the abnormal variant with disease, such as by the likelihood methods presented. The purpose of tier 3 is to confirm positive results from tier 2. Results indicate that required sample sizes are smaller when expression of disease is recessive, rather than dominant, and that, for recessive disease and large relative risks, necessary sample sizes may be feasible, even if only a small percentage of the disease can be attributed to the candidate gene. PMID- 8213836 TI - Two-trait-locus linkage analysis: a powerful strategy for mapping complex genetic traits. AB - Recent advances in molecular biology have provided geneticists with ever increasing numbers of highly polymorphic genetic markers that have made possible linkage mapping of loci responsible for many human diseases. However, nearly all diseases mapped to date follow clear Mendelian, single-locus segregation patterns. In contrast, many common familial diseases such as diabetes, psoriasis, several forms of cancer, and schizophrenia are familial and appear to have a genetic component but do not exhibit simple Mendelian transmission. More complex models are required to explain the genetics of these important diseases. In this paper, we explore two-trait-locus, two-marker-locus linkage analysis in which two trait loci are mapped simultaneously to separate genetic markers. We compare the utility of this approach to standard one-trait-locus, one-marker-locus linkage analysis with and without allowance for heterogeneity. We also compare the utility of the two-trait-locus, two-marker-locus analysis to two-trait-locus, one marker-locus linkage analysis. For common diseases, pedigrees are often bilineal, with disease genes entering via two or more unrelated pedigree members. Since such pedigrees often are avoided in linkage studies, we also investigate the relative information content of unilineal and bilineal pedigrees. For the dominant-or-recessive and threshold models that we consider, we find that two trait-locus, two-marker-locus linkage analysis can provide substantially more linkage information, as measured by expected maximum lod score, than standard one trait-locus, one-marker-locus methods, even allowing for heterogeneity, while, for a dominant-or-dominant generating model, one-locus models that allow for heterogeneity extract essentially as much information as the two-trait-locus methods. For these three models, we also find that bilineal pedigrees provide sufficient linkage information to warrant their inclusion in such studies. We also discuss strategies for assessing the significance of the two linkages assumed in two-trait-locus, two-marker-locus models. PMID- 8213837 TI - Molecular and statistical approaches to the detection and correction of errors in genotype databases. AB - Errors in genotyping data have been shown to have a significant effect on the estimation of recombination fractions in high-resolution genetic maps. Previous estimates of errors in existing databases have been limited to the analysis of relatively few markers and have suggested rates in the range 0.5%-1.5%. The present study capitalizes on the fact that within the Centre d'Etude du Polymorphisme Humain (CEPH) collection of reference families, 21 individuals are members of more than one family, with separate DNA samples provided by CEPH for each appearance of these individuals. By comparing the genotypes of these individuals in each of the families in which they occur, an estimated error rate of 1.4% was calculated for all loci in the version 4.0 CEPH database. Removing those individuals who were clearly identified by CEPH as appearing in more than one family resulted in a 3.0% error rate for the remaining samples, suggesting that some error checking of the identified repeated individuals may occur prior to data submission. An error rate of 3.0% for version 4.0 data was also obtained for four chromosome 5 markers that were retyped through the entire CEPH collection. The effects of these errors on a multipoint map were significant, with a total sex-averaged length of 36.09 cM with the errors, and 19.47 cM with the errors corrected. Several statistical approaches to detect and allow for errors during linkage analysis are presented. One method, which identified families containing possible errors on the basis of the impact on the maximum lod score, showed particular promise, especially when combined with the limited retyping of the identified families. The impact of the demonstrated error rate in an established genotype database on high-resolution mapping is significant, raising the question of the overall value of incorporating such existing data into new genetic maps. PMID- 8213839 TI - Further evidence of a relationship between the retinoic acid receptor alpha locus and nonsyndromic cleft lip with or without cleft palate (CL +/- P) PMID- 8213838 TI - Gene for the alpha-subunit of the human interleukin-3 receptor (IL3RA) localized to the X-Y pseudoautosomal region. AB - Interleukin-3 (IL3) and granulocyte/macrophage colony-stimulating factor (CSF2) stimulate proliferation and differentiation of various hemopoietic cell types. As is characteristic of the cytokine receptor family, the receptors for these proteins comprise alpha- and beta-subunits. While IL3 and CSF2 receptors each have unique alpha- subunits, they share a common beta-subunit. By Southern analysis of somatic cell hybrid panels, pulsed-field gel electrophoresis (PFGE), and fluorescence chromosomal in situ hybridization, we have mapped the cloned sequence for the IL3 receptor alpha (IL3RA) to the X-Y pseudoautosomal region at bands Xp22.3 and Yp11.3, near the gene for the alpha-subunit of the CSF2 receptor (CSF2RA). The CSF2RA and IL3RA genes are so close that their order could not be determined by two-color interphase in situ hybridization. They share PFGE fragments generated by different restriction enzymes down to the 50-100-kb size range. Pseudoautosomal inheritance was demonstrated by an EcoRI RFLP detected with the IL3RA cDNA probe. PMID- 8213840 TI - Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes. AB - Mucopolysaccharidosis type I (MPS-I) is an autosomal recessive genetic disease caused by a deficiency of the lysosomal glycosidase alpha-L-iduronidase. Hurler (severe), Scheie (mild), and Hurler/Scheie (intermediate) syndromes are clinical subtypes of MPS-I, but it is difficult to distinguish between these subtypes by biochemical measurements. Mutation analysis was undertaken to provide a molecular explanation for the clinical variation seen in MPS-I. Using chemical cleavage and direct PCR sequencing, we have defined four previously undescribed mutations for MPS-I (delG1702, 1060 + 2t-->c, R89Q, and 678-7g-->a). R89Q and 678-7g-->a were found to be present in 40% of Scheie syndrome alleles. Expression of R89Q demonstrated reduced stability and activity of the mutant protein. The deleterious effect of R89Q may be potentiated by a polymorphism (A361T) to produce an intermediate phenotype. 678-7g-->a was found to be a mild mutation, since it was present in an index Scheie syndrome patient in combination with a severe allele (W402X). This mutation appears to allow a very small amount of normal mRNA to be produced from the allele which is likely to be responsible for the mild clinical phenotype observed. Both the 5' and 3' splice site mutations (1060 + 2t-->c and 678-7g-->a, respectively) result in high proportions of mature mRNAs containing introns, which has not been observed for other splicing mutations. The frameshift mutation (delG1702) and the 5' splice site mutation (1060 + 2t-->c) are both thought to be associated with severe MPS-I. The identification of these MPS-I mutations begins to document the expected genetic heterogeneity in MPS-I and provides the first molecular explanations for the broad range of clinical phenotypes observed. PMID- 8213841 TI - Genetic heterogeneity among blue-cone monochromats. AB - Thirty-three unrelated subjects with blue-cone monochromacy or closely related variants of blue-cone monochromacy were examined for rearrangements in the tandem array of genes encoding the red- and green-cone pigments. In 24 subjects, eight genotypes were found that would be predicted to eliminate the function of all of the genes within the array. As observed in an earlier study, the rearrangements involve either deletion of a locus control region adjacent to the gene array or loss of function via homologous recombination and point mutation. One inactivating mutation, Cys203-to-Arg, was found in 15 probands who carry single genes and in both visual pigment genes in one subject whose array has two genes. This mutation was also found in at least one of the visual pigment genes in 1 subject whose array has multiple genes and in 2 of 321 control subjects, suggesting that preexisting Cys203-to-Arg mutations constitute a reservoir of chromosomes that are predisposed to generate blue-cone-monochromat genotypes by unequal homologous recombination and/or gene conversion. Two other point mutations were identified: (a) Arg247-to-Ter in one subject with a single red pigment gene and (b) Pro307-to-Leu in one subject with a single 5' red-3' green hybrid gene. The observed heterogeneity of genotypes points to the existence of multiple one- and two-step mutational pathways to blue-cone monochromacy. PMID- 8213842 TI - Classification of radiographs for pneumoconiosis: the Canadian Pneumoconiosis Reading Panel. AB - A method of providing experience for readers in the classification of radiographs for pneumoconiosis is described. It is based on an exchange of films by mail, with provision for ongoing feedback of results. The effects of this feedback on reading levels is described. The method is suitable for readers who are unable to attend major centers for formal instruction, and has the additional advantage of continual monitoring of reading levels. PMID- 8213843 TI - Asbestos-related mesothelioma in Monfalcone, Italy. AB - The Monfalcone area, in northeastern Italy, is a small industrial territory (population about 60,000), with a large shipyard. Between October 1979 and April 1992, ninety-two malignant mesotheliomas were diagnosed at the Monfalcone Hospital. The series included 84 men and 8 women, aged 42 to 89 years (median age 68 years). There were 89 pleural and 3 peritoneal tumors. Seventy patients (69 men and 1 woman) had worked in the shipyards; six were seamen, and four insulators. Five men had been exposed to asbestos in various industries; six women had histories of domestic exposure, and one woman had a history of possible environmental exposure. The latency periods (intervals between first exposure to asbestos and diagnosis of the tumor) ranged from 20 to 65 years (median 52 years). Latency periods among insulators were significantly lower than among shipyard workers, as well as lower than among the other categories (p < 0.01). Lung asbestos bodies were isolated after chemical digestion in 73 cases at necropsy, and in two cases at surgery. In necropsy cases, asbestos body burdens ranged between 100 and 10,000,000 bodies per gram of dried tissue (median 11,000). Pleural plaques were observed at necropsy in 62 out of 73 cases, and in two cases at surgery. In the time period we considered, the annual incidence rates for pleural mesothelioma were very high among male Monfalcone residents, being 189 per 100,000 among people aged 75 years or more. On the basis of occupational data and of objective signs (lung asbestos bodies, pleural plaques), all the cases of the present series but one (that with possible environmental exposure) were considered as asbestos-related. The role of co-factors in the development of asbestos-related mesothelioma is suggested. PMID- 8213844 TI - Cor pulmonale and pneumoconiotic lung disease: an investigation using hospital discharge data. AB - Cor pulmonale has been reported in the past to be associated with pneumoconiosis as an end-stage complication. However, whether the association can be demonstrated among cases of pneumoconiosis acquired in more recent decades is not clear. We examined the relation between these conditions using data summarized in hospital records in Ontario for males discharged between 1979 and 1990 with a diagnosis of chronic cor pulmonale or one of the pneumoconioses. Based on the age specific frequency rates, cor pulmonale was diagnosed 17 (95% confidence interval 13-22) times more frequently than expected among men diagnosed with pneumoconiosis than among other men admitted to hospital. Our investigation indicates that cor pulmonale still appears to be associated with dust exposure in the workplace, and it demonstrates the usefulness of hospital discharge information in addressing questions in occupational health. However, we recommend that hospital medical records be examined to confirm the diagnoses and to determine the smoking histories of these men. PMID- 8213845 TI - Median sensory distal amplitude and latency: comparisons between nonexposed managerial/professional employees and industrial workers. AB - To test for associations between occupation and median nerve dysfunction, measures of median motor and median and ulnar sensory amplitude and distal latency were compared among three populations: control subjects without occupational exposure to highly forceful or repetitive hand exertions (N = 105), industrial workers with hand/wrist symptoms (N = 103), and asymptomatic industrial workers (N = 137). Mean sensory amplitudes were significantly smaller (p < 0.05) and motor and sensory distal latencies were significantly longer (p < 0.001) in the industrial "asymptomatic hand" population compared to the control population. Prolongation of median relative to ulnar latency was significantly longer in the asymptomatic industrial population (p < 0.05). Results were most plausibly explained by differences in checklist identified ergonomic stressors. Median sensory amplitudes were significantly smaller (p < 0.01) and latencies longer (p < 0.05) for industrial workers with exposure to high grip forces compared to those without. Exposure misclassification may have reduced power to detect statistically significant differences between exposed and nonexposed population groups. PMID- 8213846 TI - Utility of the complete blood count in routine medical surveillance for ethylene oxide exposure. AB - The 1984 OSHA Standard for ethylene oxide (EtO) mandates medical surveillance under various circumstances. When performed, medical surveillance for EtO must include a complete blood count (CBC) with differential leukocyte count. This requirement is based on reports of EtO-associated absolute lymphocytosis and other hematologic effects. This paper describes our experiences in providing EtO medical surveillance for a 300 bed hospital over a 6 year period. We observed an apparent relative lymphocytosis which persisted over 3-4 years in sterilization workers with documented TWA personal EtO exposures averaging 0.07 ppm. In addition, three workers had a history of acutely toxic overexposure to EtO as a result of a sterilizer malfunction. These workers became symptomatic following the high accidental overexposure, but did not show absolute lymphocytosis or altered patterns in the relative lymphocytosis. Finally, a cross-sectional comparison of the CBC data from the EtO-exposed workers to data from non-EtO exposed hospital workers showed no significant differences, ruling out an association of the relative lymphocytosis with EtO exposure. These observations led us to review the basis for the inclusion of the CBC in routine EtO medical surveillance. Our experience, review of the literature on EtO-associated lymphocytosis and anemia, and review of the literature on the use of the CBC with differential as a screening test suggest that the leukocyte differential may not be useful in routine medical surveillance for EtO exposure. PMID- 8213847 TI - Serum IgG antibodies to mold spores in two Norwegian sawmill populations: relationship to respiratory and other work-related symptoms. AB - Wood trimmers and planing operators from two separate sawmill populations (N = 303 and 170) were studied by serology assessment and a self-administered questionnaire. IgG antibodies to Rhizopus microsporus ssp. rhizopodiformis, Paecilomyces variotii, and Aspergillus fumigatus were measured by ELISA. The questionnaire included questions about general respiratory symptoms and symptoms after handling moldy timber. Personal exposure of wood trimmers to mold spores and wood dust was measured in one part of the sawmills. R. microsporus was the most prevalent mold assessed by serology. Antibody levels were higher and symptoms suggestive of mucous membrane irritation, chronic nonspecific lung disease, allergic alveolitis, and organic dust toxic syndrome were more frequently reported by wood trimmers than by planing operators. The mean level of IgG antibodies to R. microsporus in sawmill workers working in the same work area was the best predictor of symptoms in both populations. The consistent results indicate that exposure to spores of R. microsporus may cause several respiratory symptoms in wood trimmers. PMID- 8213849 TI - Cluster of testicular cancer in police officers exposed to hand-held radar. AB - Within a cohort of 340 police officers, six incident cases of testicular cancer occurred between 1979 and 1991 (O/E 6.9; p < 0.001, Poisson distribution). Occupational use of hand-held radar was the only shared risk factor among all six officers, and all routinely held the radar gun directly in close proximity to their testicles. Health effects of occupational radar use have not been widely studied, and further research into a possible association with testicular cancer is warranted. PMID- 8213848 TI - Cancer in Illinois construction workers: a study. AB - A series of case-control studies using subjects from the Illinois State Cancer Registry have been conducted. Logistic regression was used to control for age and history of tobacco and alcohol use. Construction workers were consistently found to be younger than other subjects and to have used alcohol and tobacco more often. Significant positive associations between cancer of the stomach and welding (odds ratio [OR] = 2.11, 95% confidence interval [CI] = 1.09, 4.09), lung cancer and employment in the construction industry (OR = 1.18, 95% CI = 1.02, 1.26), and lung cancer and welding (OR = 1.68, 95% CI = 1.03, 2.76) were found. Significant negative associations between cancer of the colon and welding (OR = .54, 95% CI = .29, 1.00), cancer of the prostate and employment in the construction industry (OR = .76, 95% CI = .65, .89), cancer of the prostate and plumbing (OR = .44, 95% CI = .38, .50), cancer of the prostate and metal working (OR = .43, 95% CI = .19, .93), and bladder cancer and employment as an electrician (OR = .60, 95% CI = .36, 1.00) suggests that construction workers did not consistently experience excesses of cancers known to be associated with tobacco use, and an overall excess of sites not known to be related to tobacco use may have occurred. PMID- 8213850 TI - Technique dependent variations in asbestos burden as illustrated in a case of nonoccupational exposed mesothelioma. PMID- 8213851 TI - Epidemiologic problems related to misclassification of outcomes. PMID- 8213852 TI - Re: Work-related mesothelioma in Quebec, 1967-1990. PMID- 8213853 TI - Diagnostic bias in occupational epidemiologic studies. PMID- 8213854 TI - Re: Exposure to diesel exhaust in the trucking industry and possible relationships with lung cancer. PMID- 8213855 TI - Hazards of inexperience in swine confinement work. PMID- 8213856 TI - The rising cost of pharmaceuticals: an ethicist's perspective. PMID- 8213857 TI - New approaches to understanding and managing the rising cost of pharmaceuticals: summary remarks. PMID- 8213858 TI - Work group recommendations. PMID- 8213859 TI - The rising cost of pharmaceuticals: understanding and managing the escalating cost of pharmaceuticals in health care institutions. Executive summary. PMID- 8213860 TI - The rising cost of pharmaceuticals: an industry observer's perspective. PMID- 8213861 TI - The rising cost of pharmaceuticals: a hospital executive's perspective. PMID- 8213862 TI - The rising cost of pharmaceuticals: a director of pharmacy's perspective. PMID- 8213863 TI - The rising cost of pharmaceuticals: a physician's perspective. PMID- 8213864 TI - Why new definitions of sepsis and organ failure are needed. PMID- 8213865 TI - Ehrlichiosis presenting as a life-threatening illness with features of the toxic shock syndrome. AB - OBJECTIVE: To describe clinical and laboratory features of patients with severe ehrlichiosis, some of whom presented with toxic shock syndrome (TSS)-like illnesses, and to report, to our knowledge, the first documented fatal case of ehrlichiosis in a child. DESIGN: Case series. SETTING: Tertiary-care medical center. PATIENTS: All patients with documented ehrlichiosis during a 3-year period, August 1, 1989, to July 31, 1992. RESULTS: Eight patients (age range: 2 to 46 years) met clinical and serologic diagnostic criteria for ehrlichiosis. The mean interval from first contact with a physician to initiation of appropriate antibiotic therapy was 4.6 days (range: 1 to 11 days). All eight patients with ehrlichiosis had fever, chills, thrombocytopenia, and abnormal liver function test results. Most patients also had rash (seven), conjunctival hemorrhage or erythema (six), and leukopenia (six). Four cases met diagnostic criteria for TSS with fever, hypotension, rash, and multiorgan dysfunction. Two patients required mechanical ventilation, and one of these, a 6 1/2-year-old boy, died of complications of the infection. A ninth patient with probable ehrlichiosis also met diagnostic criteria for TSS. CONCLUSIONS: Human ehrlichiosis can present as a severe, life-threatening illness that may resemble TSS. The diagnosis of ehrlichiosis was not considered by the physicians who first cared for these patients. Greater awareness of the potential severity of ehrlichiosis is needed to ensure that proper treatment is initiated early in the course of the disease. PMID- 8213866 TI - Utility of bronchoalveolar lavage in assessing pneumonia in immunosuppressed renal transplant recipients. AB - PURPOSE: To determine if initial results obtained from diagnostic bronchoalveolar lavage (BAL) in immunosuppressed renal transplant patients with pulmonary infiltrates, fever, or hypoxemia can affect therapeutic decisions, morbidity, and mortality. DESIGN: A retrospective study of all BAL specimens obtained from renal transplant patients from January 1985 through June 1991. Initial results of Gram stain, cytology, cell differential count, and semi-quantitative bacterial cultures, all available within 24 hours of bronchoscopy, were compared with clinical outcomes and final diagnoses. SETTING: University hospital nephrology transplant/pulmonary service. PATIENTS: Seventy renal transplant patients with a suspected pneumonia were stratified into 3 groups. A total of 48 patients underwent 58 bronchoscopies. Group 1 was comprised of 32 BALs that yielded 1 or more infectious organisms and was considered diagnostic. Group 2 (n = 26) were those BALs in which no organism was isolated and were thus nondiagnostic. Twenty two additional immunosuppressed renal transplant recipients with pneumonia were considered by the admitting transplant nephrologist to have an uncomplicated community-acquired lung infection and thus were empirically treated and did not undergo BAL (Group 3). METHODS: BAL fluid analysis included cell differential count, cytopathologic examination, and culture for mycobacteria, legionella, fungi, viruses, and bacteria using a semi-quantitative technique. Etiologic diagnosis and the time of onset of the infectious processes were recorded. Therapeutic outcome and mortality were determined for each group. RESULTS: Thirty nine etiologic organisms were found in 32 patients, with 6 patients having more than 1 infection. Twenty-two patients had 26 negative BALs, and 8 of these patients were clinically believed to have a volume overload state. Eight of 13 (61%) patients with bacterial pneumonia had BAL neutrophil counts greater than 20%, whereas 11 of 13 (84%) patients without bacterial pneumonia had neutrophil counts less than 20% (p < 0.05). Those patients with an infectious etiology remained in the hospital longer than patients without a specific etiologic organism identified (p < 0.02). Therapeutic decisions leading to the institution of specific antibiotics were more frequently made in patients with a diagnostic BAL (p < 0.0001). An overall 3-month mortality (16%) was low compared with the historical rate (30%). CONCLUSION: BAL is a useful procedure in the diagnosis of an infectious process in immunosuppressed renal transplant patients where initial results can alter therapy in more than 70% of cases. PMID- 8213867 TI - Catheter-related Malassezia furfur fungemia in immunocompromised patients. AB - PURPOSE, PATIENTS, AND METHODS: Malassezia furfur has usually been described as a cause of catheter-related sepsis in neonates receiving intravenous lipid emulsion. We report seven cases of catheter-related M. furfur fungemia that occurred in seven immunocompromised patients including four adults and three children who were not neonates. Only two of these patients were receiving concurrent intravenous lipid emulsion. RESULTS: All positive blood cultures were obtained from a central venous access device, one of which was a port device. Quantitative M. furfur colony counts ranged from 50 cfu/mL to greater than 1,000 cfu/mL. All seven patients were treated with amphotericin B. Blood drawn through the central lines of three patients yielded additional organisms. One central venous access device required removal due to persistently positive M. furfur blood cultures despite treatment with amphotericin B. CONCLUSION: We conclude that catheter-related M. furfur fungemia occurs in immunocompromised patients with central venous access devices whether or not they are receiving intravenous lipids. Prompt, aggressive treatment with amphotericin B (1 mg/kg/d) may spare patients removal of their central venous access device. Further studies are needed to determine the role of endogenous lipids in the development of catheter related M. furfur fungemia and to determine if there is a seasonal incidence in populations other than neonates, since all of our cases occurred between late March and July. PMID- 8213868 TI - Assessment of early post-infarction ischemia: correlation between ambulatory electrocardiographic monitoring and exercise treadmill testing. AB - PURPOSE: Demand-related myocardial ischemia detected by treadmill testing is commonly used to identify high-risk patients after myocardial infarction (MI). Although ischemia detected by ambulatory electrocardiographic monitoring (AECG) has also been shown to predict poor outcome in some patient groups, the relationship between AECG-detected ischemic ST changes and post-MI treadmill ischemia is unknown. PATIENTS AND METHODS: We screened 94 patients after MI with 24-hour AECG monitoring and a Naughton treadmill test. Forty-two patients were excluded because of left bundle branch block, left ventricular hypertrophy, abnormal baseline ST segments, or digoxin therapy. In the remaining 52 patients, AECG was performed 5.1 +/- 2.2 days after MI (mean +/- SD) and the treadmill test 8.4 +/- 2.2 days after MI. Each patient was taking the same drugs for both studies, had no interim revascularization procedures, and all studies were interpreted blindly. RESULTS: The treadmill test (ETT) was positive for ST changes and/or thallium reperfusion defects in 19 of 52 patients (36%). The AECG was positive for ischemia (ST depression greater than 1 mm, for more than 1 minute) in 14 of 52 patients (27%) (Group I), with 9.9 +/- 8.2 ischemic episodes per patient lasting 13.5 +/- 7.5 minutes per episode. The AECG was negative for ischemia in the remaining 38 patients (73%) (Group II). The ETT and AECG correlation was as follows: 9 patients with AECG-detected ischemic ST changes had positive ETT results; 10 patients without AECG-detected ischemic ST changes had positive ETT results; 5 patients with AECG-detected ischemic ST changes had negative ETT results; and 28 patients without AECG-detected ischemic ST changes had negative ETT results (p < 0.02 by chi 2). The predictive accuracy of a positive AECG identifying a positive ETT was 65% (specificity 85%, sensitivity 47%), and the predictive accuracy of a negative AECG identifying a negative ETT was 74%. Group I patients were older than Group II patients (63.6 +/- 8.2 years versus 53.2 +/- 10.6 years p < 0.02), more commonly had painless ETT ischemia (43% versus 18% p = 0.08), and tended to have positive ETT results at a lower level of exercise (366 +/- 210 seconds versus 588 +/- 212 seconds, p = 0.04). CONCLUSION: Ischemic ST changes as detected by AECG monitoring correlate significantly with post-MI treadmill test results with a high specificity, albeit a low sensitivity. In patients without baseline ST-segment abnormalities and limited exercise capability, AECG monitoring may be of limited use in identifying early post-MI ischemia. PMID- 8213869 TI - Clinical and laboratory features of measles in hospitalized adults. AB - PURPOSE: Description of the epidemiology, morbidity, and mortality of hospitalized adults with typical measles. PATIENTS AND METHODS: Retrospective case analysis of 33 adults who required acute care for complications of measles in a public hospital in Los Angeles, California. The diagnosis of measles was established on standard clinical or serologic grounds. RESULTS: Of 68 patients (age greater than 14) with signs and symptoms of measles who presented for medical care, 33 (19 males and 14 females) required hospitalization; 18 were natives of the United States. The patient age was 26.1 +/- 7.3 (mean +/- SD) years; four patients, all natives of the U.S., were born before 1957. The duration of hospitalization was 6.8 +/- 8.8 days for all patients and 13.4 +/- 14.2 days for the nine patients who required intensive care unit (ICU) care. Six of the ICU patients required mechanical ventilation for 11.0 +/- 15.0 days; two deaths occurred among these patients. During the course of their illness, 7 of 25 (28%), 11 of 28 (39%), 6 of 28 (21%), and 5 of 16 patients (31%) had peak lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and creatine kinase values, respectively, that were greater than 5 times the upper limit of normal. Fifteen of 28 patients (54%) developed total serum calcium levels less than or equal to 2.0 mmol/L. Ten cases were serologically confirmed; 23 cases were diagnosed as probable measles on clinical grounds. There were no significant demographic, clinical, or laboratory differences between patients with confirmed and probable measles. No patients had characteristic manifestations of atypical measles. The sole immunocompromised patient died. CONCLUSIONS: Measles in adults may result in severe, life-threatening complications that utilize substantial medical resources. Physicians need to appreciate the clinical presentations and manifestations of severe measles in adults and to provide measles vaccine to nonimmune adults during community-wide outbreaks. PMID- 8213870 TI - Bone density is not reduced during the short-term administration of levothyroxine to postmenopausal women with subclinical hypothyroidism: a randomized, prospective study. AB - PURPOSE: Controversy exists as to whether patients with subclinical hypothyroidism benefit from treatment. Two randomized trials reported that hypothyroid symptoms improved following thyroid hormone replacement therapy. However, during the initial treatment of overt hypothyroidism with levothyroxine, three studies have demonstrated short-term (6 to 12 months) 5% to 13% reductions in bone density. The current study measures bone density during the initial treatment of subclinical hypothyroidism. PATIENTS: Seventeen postmenopausal women with subclinical hypothyroidism (elevated serum thyrotropin [TSH] and normal serum free thyroxine concentrations) and no prior history of thyroid disease were randomly assigned to levothyroxine treatment or no treatment and followed prospectively. Patients in the treatment group had similar initial serum TSH concentrations (9.8 +/- 3.3 versus 8.4 +/- 2.7 microU/mL) but were slightly older (68 +/- 7 years versus 60 +/- 5 years [p < 0.02]). The average dose of levothyroxine needed to normalize serum TSH concentration was 0.072 +/- 0.027 mg. RESULTS: Bone density determinations were not significantly different between the two groups at baseline. After 14 +/- 1 months, single-photon absorptiometry of the wrist decreased by 1.8% +/- 3.2% in the untreated patients and 0.5% +/- 4.1% in the levothyroxine-treated patients (p = NS). Dual-energy X-ray absorptiometry of the lumbar spine decreased by 0.7% +/- 2.9% in the untreated patients and rose 0.1% +/- 4.75% in the levothyroxine-treated patients (p = NS). CONCLUSIONS: Unlike the early treatment of overt hypothyroidism, there is no short-term reduction of bone density with levothyroxine treatment of subclinical hypothyroidism in postmenopausal women. These data suggest that potentially symptomatic women with subclinical hypothyroidism should be given a trial of levothyroxine therapy without concern about adverse effects on skeletal integrity. PMID- 8213871 TI - Teaching cardiovascular examination skills: results from a randomized controlled trial. AB - PURPOSE: To evaluate the effectiveness of a teaching program designed to improve interns' cardiovascular examination skills. PARTICIPANTS: All 56 interns rotating on a mandatory 4-week inpatient cardiology service during 1 academic year (July 1989-June 1990). METHODS: We randomly assigned interns to receive either an eight session physical diagnosis course ("teaching group") taught on the cardiology patient simulator ("Harvey") or to receive no supplemental teaching ("control group"). Before and immediately after the teaching or control period, the interns were evaluated on three preprogrammed simulations (mitral regurgitation, MR; mitral stenosis, MS; aortic regurgitation, AR). Immediately after the control or the intervention period, the interns also evaluated patient volunteers. RESULTS: There were no baseline differences in the interns' ability to correctly identify the disease simulations. Both the intervention and the control interns showed similar, moderate improvement in their diagnostic ability on the simulator. The intervention interns improved on MR from 42% correct to 54% correct; on MS from 8% correct to 23% correct; and on AR from 46% correct to 58% correct. The intervention and the control interns performed similarly on patient volunteers: for MR, 20% correct versus 31%; for AR, 29% correct versus 33%; and for aortic sclerosis, 64% correct versus 33%, respectively. CONCLUSIONS: The interns had difficulty correctly identifying three valvular heart disease simulations before and after an educational intervention employing a cardiovascular-patient simulator. At no time did the proportion of correct responses exceed 64%. Our teaching intervention during internship was either of insufficient intensity or of insufficient duration to produce significant improvement in cardiovascular diagnostic skills. PMID- 8213872 TI - Effect of pelvic irradiation on gastrointestinal function: a prospective longitudinal study. AB - PURPOSE: Although radiation enteritis is a well-recognized sequel of therapeutic irradiation, the effects of abdominal and/or pelvic irradiation on gastrointestinal function are poorly defined and treatment is often unsuccessful. To determine both the short- and long-term effects of therapeutic irradiation on gastrointestinal function, we performed a prospective study. PATIENTS AND METHODS: Various aspects of gastrointestinal function were evaluated in 27 patients with potentially curable malignant disease (23 female, 4 male) before the commencement of, during, and 6 to 8 weeks, 12 to 16 weeks, and 1 to 2 years following completion of radiation therapy. Seventeen patients received pelvic irradiation alone and 10 patients received both abdominal and pelvic irradiation. Gastrointestinal symptoms, absorption of bile acid, vitamin B12, lactose, and fat, gastric emptying, small-intestinal and whole-gut transit, stool weight, and intestinal permeability were measured. Results were compared with those obtained in 18 normal volunteers. RESULTS: All 27 patients completed at least 2 series of measurements and 18 patients completed all 5 series of experiments. During radiation treatment, increased stool frequency (p < 0.001) was associated with decreased bile acid and vitamin B12 absorption (p < 0.001 for both), increased fecal fat excretion (p < 0.05), an increased prevalence of lactose malabsorption (p < 0.01), and more rapid small-intestinal (p < 0.01) and whole-gut (p < 0.05) transit. Although there was improvement in most of these changes with time, at 1 to 2 years after the completion of irradiation, the frequency of bowel actions was greater (p < 0.001), bile acid absorption was less (p < 0.05), and small intestinal transit was more rapid (p < 0.01) when compared with that of baseline and the normal subjects. At this time, at least 1 parameter of gastrointestinal function was abnormal in 16 of the 18 patients. Stool weight was greater (p < 0.05) and whole-gut transit faster (p < 0.01) in patients who received both pelvic and abdominal irradiation, when compared with those who received pelvic irradiation alone. Stool frequency (p < 0.001) and fecal fat excretion (p < 0.05) were greater in those patients who had surgery before radiation therapy. CONCLUSION: Pelvic irradiation is usually associated with widespread, persistent effects on gastrointestinal function. PMID- 8213873 TI - Serum angiotensin-converting enzyme as a marker for the chronic fatigue-immune dysfunction syndrome: a comparison to serum angiotensin-converting enzyme in sarcoidosis. AB - PURPOSE: To study the reliability of a serum angiotensin-converting enzyme (ACE) assay as a marker for the chronic fatigue-immune dysfunction syndrome (CFIDS), and to compare some enzyme characteristics of ACE in CFIDS with that in sarcoidosis. PATIENTS AND METHODS: Forty-nine patients with CFIDS and 56 endemic control subjects from Lyndonville, New York, and Charlotte, North Carolina; plus 23 untreated patients with active sarcoidosis, 24 with sarcoidosis receiving corticosteroid therapy, and 32 patient controls without sarcoidosis from California. Serum ACE levels were determined with a spectrophotometric method. The effect of freezing and thawing and the effect of storage at 4 degrees C were compared between CFIDS and sarcoidosis samples. RESULTS: Serum ACE levels were elevated in 80% of patients with CFIDS and 30% of endemic control subjects as compared with 9.4% of nonendemic California control subjects. The ACE activity in CFIDS differed from that in sarcoidosis because of its lability with storage at 4 degrees C in CFIDS and its partial activation with freezing and thawing. Thus, ACE activity was elevated in the majority of CFIDS patients either upon initial assay or upon a subsequent assay after refreezing. ACE activity was elevated in 87% of patients with active sarcoidosis and was not affected by storage or freezing and thawing. CONCLUSIONS: Serum ACE elevations may be a useful marker for CFIDS, especially if a method can be developed to distinguish ACE in CFIDS from that in sarcoidosis. The sensitivity for CFIDS was 80%, with 68% specificity in an endemic area. The increased prevalence of serum ACE elevations in endemic controls as compared with nonendemic controls suggests that an ACE increase may be an early manifestation of CFIDS and supports the concept that CFIDS is a definite disease state. PMID- 8213874 TI - Failure of the circulatory system limits exercise performance in patients with systemic sclerosis. AB - OBJECTIVE: To determine the mechanisms for exercise impairment in symptomatic patients with systemic sclerosis (SSc) using breath-by-breath expired-gas analysis with incremental exercise testing. DESIGN: Prospective, open trial. PATIENTS AND METHODS: Fifteen consecutive patients with SSc seen at the Medical University Hospital (a tertiary referral center) with complaints of exercise intolerance underwent pulmonary function testing (spirometry, helium dilution lung volumes, and diffusing capacity of carbon monoxide) and incremental exercise testing on a cycle ergometer measuring oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (R), oxygen saturation, blood pressure, and heart rate (HR). Values for oxygen uptake at anaerobic threshold (VO2AT) were derived graphically by blinded clinicians experienced in exercise testing, and the results were averaged. Ventilatory reserve and oxygen pulse were calculated from measured values, and all data were subjected to analysis by standard clinical algorithms. MEASUREMENTS AND MAIN RESULTS: Of 15 patients studied, 14 had either restrictive lung disease or normal results of spirometry on pulmonary function testing. One patient with a history of tobacco use had evidence of airways obstruction. Three patients were unable to exercise maximally (as determined by maximum respiratory exchange ratio [Rmax] greater than 1.09 or maximum heart rate [HRmax] greater than 85% predicted), and exercise testing was terminated in one with Mobitz type II atrioventricular block. The following data (mean +/- SEM) were obtained from 11 maximally exercising patients: VO2max 795 +/ 75 mL oxygen (O2)/min, R 1.34 +/- 0.05, VO2AT/VO2max predicted 0.21 +/- 0.02, O2 pulse 5.1 +/- 0.4 mL O2/beat, ventilatory reserve 0.52 +/- 0.06, and tidal volume/forced vital capacity ratio 0.46 +/- 0.02. Of the 11 patients completing breath-by-breath expired-gas analysis, all had circulatory impairment to exercise, as determined by low O2 pulse and low VO2 at anaerobic threshold, and circulatory impairment was limiting in 9 of 11 patients. Of those nine patients, four had evidence of impaired gas exchange compatible with pulmonary vascular disease. Arterial oxygen desaturation occurred in 2 of 11 patients. CONCLUSION: Circulatory impairment to exercise is common in SSc patients with exercise intolerance. Restrictive lung disease, although also common, does not limit exercise tolerance in patients capable of maximal effort. PMID- 8213875 TI - Groshong catheter-associated subclavian venous thrombosis. AB - PURPOSE: To identify factors associated with the development of clinically significant venous thrombosis in cancer patients with long-term indwelling subclavian Groshong catheters (GC). Also, to assess both the subsequent performance of affected catheters and the effect of heparin and warfarin therapy on subsequent catheter function and longevity. METHODS: Longitudinal study of the outcome of clinical practice. Subset analysis of those catheters developing catheter-related venous thrombosis (CRVT). RESULTS: Thirty-seven cases of CRVT were identified in a population of 255 consecutive patients in whom a GC was inserted. Seventy percent of the thrombi occurred after an episode of previous catheter dysfunction; only 30% of the thrombi occurred de novo. An unexpectedly high risk of thrombosis was associated with insertion into the left-subclavian circulation (25 of 35 versus 135 of 220, p = 0.02) or with an antecedent episode of aspiration difficulty ("ball-valve effect" [BVE]) (20 of 35 versus 60 of 220, p < 0.01). No correlation was identified between thrombosis and tumor type, tumor histology, or preexisting medical disorders. Once identified, 79% of the involved patients received anticoagulant therapy with sequential heparin and warfarin. Overall longevity of the catheters preserved by anticoagulation (mean dwell = 202 days) far exceeded catheter longevity among the population of catheters that never developed thrombosis (mean dwell = 142 days). The mean catheter longevity after thrombosis (169 days) also exceeded the mean dwell time of all other catheters that were complication-free. CONCLUSIONS: CRVT is more likely in patients in whom the catheter is inserted in the left-subclavian circulation or who have experienced a previous episode of aspiration difficulty with the catheter (BVE). Catheter preservation with sequential heparin and warfarin therapy precludes the need for catheter removal and extends dramatically the useful life of the catheter. PMID- 8213876 TI - Vascular abnormalities in non-insulin-dependent diabetes mellitus identified by arterial waveform analysis. AB - PURPOSE: The arterial pressure waveform is derived from the complex interaction of the left ventricular stroke volume and the physical properties of the arterial circulation. Widespread abnormalities in the physical characteristics of the arterial vessels associated with diabetes mellitus can produce consistent changes in the shape of the pressure pulse waveform, providing information about arterial structure and tone that can be quantitated by pulse contour analysis. PATIENTS AND METHODS: We analyzed intraarterial brachial artery waveforms in 28 patients with non-insulin-dependent diabetes mellitus and 22 control subjects matched for age and sex. A computer-based assessment of the diastolic pressure decay and a modified Windkessel model of the circulation were employed to quantify changes in arterial waveform morphology in terms of the large-artery compliance (C1), the oscillatory diastolic waveform (C2), inertance, and systemic resistance. RESULTS: No differences were found in heart rate, mean arterial pressure, cardiac output, or stroke volume between groups. The mean oscillary arterial compliance estimate was significantly reduced in diabetic subjects versus controls: 0.02 (95% confidence interval [CI], 0.01 to 0.03) mL/mm Hg versus 0.08 (95% CI, 0.04 to 0.12) mL/mm Hg (p < 0.001). Oscillatory compliance values were uniformly reduced in the diabetic subjects regardless of the presence or absence of physical complications of the disease. No differences in large-artery compliance, inertance, or systemic resistance were found between groups. No positive correlations were found between indices of glycemic control, the known duration of diabetes, and any of the hemodynamic variables. CONCLUSIONS: Quantitative changes in the arterial pressure pulse waveform, reflected by a reduced oscillatory compliance estimate, were found in patients with non-insulin dependent diabetes mellitus. This estimate appears to act as an early marker for the vascular abnormalities associated with diabetes before complications of the disease become clinically apparent. By contrast, no changes in large-artery compliance were found in this patient population free from clinically obvious macrovascular disease. PMID- 8213877 TI - Verapamil intoxication: a literature review of overdoses and discussion of therapeutic options. AB - Calcium channel antagonists can be quite toxic. In the management of poisoning, early recognition is critical. Calcium channel antagonists are frequently prescribed, and the potential for serious morbidity and mortality with overdosage is significant. Ingestion of these agents should be suspected in any patient who presents in an overdose situation with unexplained hypotension and conduction abnormalities. The potential for toxicity should be noted in patients with underlying hepatic or renal dysfunction who are receiving therapeutic doses. Because there is no specific antidote, decontamination of the gastrointestinal tract is crucial. Intravenous calcium should be administered to symptomatic patients because it is relatively innocuous and may be beneficial. Volume expansion should be the initial approach to hypotension unrelated to bradycardia. Patients who have had a verapamil overdose should be observed in intensive care units where Swan-Ganz catheterization and ventricular pacing are routinely available. The choice of sympathomimetic agents for treatment remains controversial. According to the published literature, isoproterenol, epinephrine, and norepinephrine may be more effective in improving bradycardia and the resultant hypotension than dopamine. However, none of these agents is universally effective. A more logical approach may be to improve cardiac output with agents like amrinone. Bay K 8644 and 4-aminopyridine show promise as potential antidotes but at present are still experimental. PMID- 8213878 TI - Formation of neutralizing antibodies after treatment with human calcitonin. AB - PURPOSE: Calcitonin is used for the treatment of Paget's disease of bone, hypercalcemia, and postmenopausal osteoporosis. The formation of antibodies against heterologous calcitonins, such as salmon calcitonin (sCT), has been described frequently. Neutralizing effects of these antibodies have been demonstrated in many cases. As far as antibody formation against human calcitonin (hCT) is concerned, only a single case has been reported in the literature; however, investigations concerning the biologic activity of the antibodies were not performed. We have now assessed the sera of 33 patients treated with hCT for postmenopausal osteoporosis for a period of at least 12 months to evaluate the occurrence of hCT-binding and hCT-neutralizing antibodies. PATIENTS AND METHODS: Binding antibodies were detected by incubation of patient sera with 125I-labeled hCT; neutralizing activity was assessed in an in vitro bioassay that measured the impairment of the hCT-induced cyclic adenosine monophosphate (cAMP) formation in the human breast cancer cell line T47D. RESULTS: Prior to hCT treatment, none of the patients showed evidence of the presence of either binding or neutralizing antibodies. During the course of treatment, binding antibodies occurred in a single patient. These antibodies had a neutralizing activity characterized by 15% impairment of cAMP formation after 6 months and 27% impairment after 12 months of treatment compared with pretreatment control values. The neutralizing effect observed in this particular patient was comparatively mild compared with the effects seen after the formation of neutralizing antibodies against sCT, so major clinical sequelae were not expected in this patient. This may be due to the lower antigenicity of hCT as compared with sCT. CONCLUSION: Although antibody formation against hCT is a rare phenomenon, we nonetheless recommend monitoring of postmenopausal osteoporosis patients treated with sCT or hCT for neutralizing antibody formation in order to evaluate the therapeutic effect of treatment. PMID- 8213879 TI - Syncope and cardiac arrhythmia due to an interaction between itraconazole and terfenadine. PMID- 8213880 TI - Pheochromocytoma presenting as a prolonged attack of Chinese restaurant syndrome. PMID- 8213881 TI - Misinterpretation of serum transaminase elevation in "occult" myositis. PMID- 8213882 TI - Group III acute bacterial nephritis. PMID- 8213883 TI - Pneumococcal endocarditis on an artificial mitral valve. PMID- 8213884 TI - Stenosis of the lingual artery. PMID- 8213885 TI - Skin necrosis due to vitamin K deficiency. PMID- 8213886 TI - Clinical significance of anaerobic bacteremia in a Veterans Affairs medical center. PMID- 8213887 TI - Human T lymphotropic virus type II (HTLV-II) infection among female prostitutes in Yucatan, Mexico. AB - The antibodies to human T-lymphotropic virus type I/II (HTLV-I/II) were determined in non-intravenous drug-using female prostitutes from Merida Yucatan, Mexico. Serum specimens from 282 female prostitutes collected during 1990 were tested initially by enzyme immunoassay and further confirmed by western blot assays. Of these, 5 (1.8%, 95% confidence interval 0.2 to 3.3) were shown to be HTLV-I/II positive (reactivity to p24gag and gp68/r21eenv). All five specimens were shown to be infected with HTLV-II by immunoassays using type-specific synthetic peptides and recombinant proteins. Long-term cell lines developed from two individuals demonstrated active viral replication and were of CD8 phenotype. Polymerase chain reaction analysis from four of these five prostitutes demonstrated HTLV-II-specific amplification of all four specimens, of which one was subtype a (HTLV-IIa) and three were subtype b (HTLV-IIb). These data show that HTLV-II is the predominant HTLV type among female prostitutes from the Yucatan. PMID- 8213888 TI - Protein S levels during the normal menstrual cycle and during estrogen therapy for premature ovarian failure. AB - Protein S levels have been reported to be decreased in pregnancy and with oral contraceptive use. This study monitored the effects of estrogen shifts on protein S levels. Four patients with premature ovarian failure were treated with either oral or transdermal patch estrogen replacement. Blood drawn on days 1, 14, and 28 of therapy was analyzed for estradiol, estrone, free and total protein S, and C4b binding protein (C4b-BP) levels. Similar studies were performed on six normally cycling control patients and seven postmenopausal women. In healthy females, total levels of protein S fell from 22.1 +/- 0.73 micrograms/mL on day 1 to 19.2 +/- 1.29 micrograms/mL on day 14 (p < 0.023). Free protein S levels declined from 6.45 +/- 0.70 micrograms/mL to 5.59 +/- 0.69 micrograms/mL (p < 0.016). C4b-BP levels did not change during the normal menstrual cycle. Baseline total protein S (44.1 +/- 7.0 micrograms/mL) and C4b-BP (193 +/- 18%) levels were elevated in patients with premature ovarian failure. On oral therapy, there was a strong, negative correlation (r = -0.979, p < 0.021) between C4b-BP and estradiol levels. C4b-BP levels did not change in patients with the patch. Both estrogen therapies produced similar declines (44 to 26 micrograms/mL) in total protein S levels. In all cases, total protein S levels changed as a reciprocal function of estradiol. C4b-BP (128 +/- 6.5%) and total protein S (32.2 +/- 3.0 micrograms/mL) levels were higher in postmenopausal women than in nonmenopausal females. Free protein S levels in postmenopausal women (9.6 +/- 0.6 micrograms/mL) were normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213889 TI - Augmented central pressor action of magnesium in SHR. AB - This study attempted to determine whether central magnesium (Mg) influences the regulation of blood pressure (BP). An intracerebroventricular (icv) injection of a high Mg2+ solution (190.0 mEq/L, 10 microL), made by adding MgC12 to artificial cerebrospinal fluid, increased the mean BP in both conscious spontaneously hypertensive rats (SHR; n = 17, p < 0.001) and Wistar Kyoto rats (WKY; n = 8, p < 0.005). Spontaneously hypertensive rats showed a greater pressor response than WKY (+11.7 +/- 0.9 mm Hg versus +3.5 +/- 1.1 mm Hg, p < 0.001). This pressor response to Mg2+ given icv was dose-dependent in the range of Mg2+ concentration between 47.5 and 190.0 mEq/L in SHR. A high Mg2+ solution (190.0 mEq/L), made by adding MgSO4 given icv, also increased the mean BP in SHR (n = 7, p < 0.001) and WKY (n = 6, p < 0.01), whereas the high osmolarity solution (340 mOsm/kg H2O) given icv did not change the mean BP in either SHR or WKY. Also administered was a high Mg2+ solution icv after either hexamethonium bromide (Hx; 50 mg/kg intravenously) or arginine vasopressin antagonist (aAVP, (CH2)5Tyr(Me)AVP, 30 micrograms/kg i.v.). The pressor response to the high Mg2+ solution was abolished by arginine vasopressin antagonist both in SHR and WKY, although it was not canceled by Hx. A high Mg2+ solution administered icv caused a 3.5-fold increase in plasma arginine vasopressin concentration in SHR (n = 5, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213890 TI - Fungemia in patients with leukemia. AB - A nine-year retrospective study on fungemia in patients with leukemia was conducted. A total of 79 episodes of fungemia in 77 patients with leukemia were documented. Candida parapsilosis fungemia was associated more frequently with the presence of a central venous line and to the use of parenteral nutrition than the other fungal species (p = 0.00026 and p = 0.01, respectively). The same fungus was isolated from both blood and surveillance cultures in 95% of Candida albicans and in 89% of Candida tropicalis fungemia (p < 0.01 and p = 0.02, respectively). The neutropenia and fungus colonization that resulted was associated significantly with the presence of invasive disease (p = 0.0024 and p = 0.0028, respectively). Conversely, central venous catheterization and parenteral nutrition appeared to be associated with episodes without deep tissue invasion (p = 0.000037 and p = 0.001, respectively). Invasive mycosis due to the fungus isolated from blood was documented in 51 patients with a mortality rate of 69%, whereas in 20 patients without invasive mycosis, mortality rate was 21% (p = 0.000059). In patients with fungemia, related or unrelated to the presence of a central venous catheter, mortality was 24% and 64%, respectively (p = 0.00042). Mortality was highest with C. tropicalis (p = 0.0017) and lowest with C. parapsilosis (p = 0.057). Severe neutropenia (polymorphonuclears < 100/mmc) appeared associated with a higher mortality rate (p = 0.012), whereas the recovery of neutropenia was related adversely to a fatal outcome (p < 0.01). With antifungal therapy, there was no statistically significant difference whether antifungal therapy was given or not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8213891 TI - Case report: spinal cord compression due to metastatic hepatocellular carcinoma. AB - Hepatocellular carcinoma is an uncommon cancer in the United States. Its initial presentation as spinal cord compression due to vertebral metastasis is rare. This article reports a case of radiculopathy and rapidly developing spinal cord compression because of bony metastasis from this form of liver cancer. This article also reviews pertinent literature and discusses the diagnostic modalities for early detection. PMID- 8213892 TI - Case report: bacillary angiomatosis with massive visceral lymphadenopathy. AB - Bacillary angiomatosis is a newly characterized infectious disease occurring mainly in patients with AIDS. Most patients have cutaneous angiomatosis lesions resembling Kaposi's sarcoma or pyogenic granuloma. Although the disease may be life-threatening if not treated, it is curable with appropriate antibiotic therapy. A patient had a fever, nightsweats, abdominal pain, pleural effusions, and asymmetric peripheral lymphadenopathy. Computed tomography of the chest and abdomen revealed a unique pattern of enhancement of lymph nodes that, to this research team's knowledge, has not been reported previously with this condition. Appropriate antibiotic therapy resulted in a complete resolution of the disease. Included is a discussion of the clinical presentation, etiology, histology, and treatment of bacillary angiomatosis. PMID- 8213893 TI - Radiofrequency catheter ablation for the management of cardiac tachyarrhythmias. AB - Radiofrequency catheter ablation techniques allow for safe and highly effective curative therapy of a variety of cardiac dysrhythmias. The technique involves the delivery of a high-frequency, alternating electrical current through an intravascular catheter to sites of arrhythmogenic myocardium. This current induces resistive electrical heating of the tissue, resulting in discrete areas of myocardial destruction through coagulation and desiccation. Dysrhythmias most commonly treated with these techniques are atrioventricular nodal reentry and tachycardias related to accessory atrioventricular bypass tracts. For these dysrhythmias, success rates of 90% to 95% are achievable with a low (2% to 4%) risk of complications. Radiofrequency catheter ablation techniques also have been used to treat ventricular tachycardias, atrial flutter, ectopic atrial tachycardia, and sinus node reentry, albeit with lower success rates. These techniques are still evolving, alternate energy sources (such as microwave and laser) and improved catheter technology should enhance the technique's safety and efficacy for a wider range of dysrhythmias. PMID- 8213894 TI - Diagnosis and treatment of the major hepatotropic viruses. AB - The hepatotropic viruses currently include hepatitis A, B, C, D, and E, and are associated with a spectrum of acute and chronic liver disease syndromes. The epidemiology and natural history of each are discussed, with emphasis on uncommon or newly recognized clinical presentations. The serodiagnosis of hepatitis A, B, and D is well established; the serodiagnosis of hepatitis C and E continues to evolve as serologic and virologic assays become refined. Hepatitis A and E only cause acute liver injury; current medical approaches therefore focus on vaccination strategies. Hepatitis B, C, and D can cause both acute and chronic liver injury. Sequelae of chronic liver disease, including portal hypertension and hepatocellular carcinoma, are not uncommon. Medical therapy of resulting chronic liver disease currently consists of interferon, though other anti-viral strategies are being explored. Advanced chronic liver disease due to hepatitis B, C, or D can be treated by orthotopic liver transplantation, but viral recurrence is near uniform and can be problematic. Further study of the hepatotropic viruses at the molecular biologic, epidemiologic, and clinical levels will continue to provide greater insight into the diagnosis and management of their associated clinical syndromes. PMID- 8213895 TI - Incidental pituitary adenomas. AB - Because adenomas of the pituitary are present in 10% to 20% of healthy individuals, the finding of incidental sellar lesions on computed tomography scanning or magnetic resonance imaging has become relatively common. Hyperfunctioning of such lesions can be excluded clinically and by hormonal screening. Hypopituitarism must be excluded only in lesions more than 10 mm in diameter. Although most such lesions are pituitary adenomas, other lesions such as craniopharyngiomas, meningiomas, and metastatic disease also must be considered. In the absence of visual field defects or hypothalamic/stalk compression, it may be appropriate to follow these patients with repeat imaging. If tumors enlarge, surgery is indicated. PMID- 8213896 TI - Southwestern internal medicine conference: restenosis: the Achilles heel of coronary angioplasty. AB - Percutaneous transluminal coronary angioplasty has become the treatment of choice for many patients with symptomatic coronary artery disease. Increased experience with the procedure and improvements in equipment have resulted in high initial success rates; however, a significant number of patients develop restenosis. Insights into the pathophysiologic mechanisms of restenosis have led to the use of various pharmacologic agents and devices to prevent its occurrence. Although many have been successful in decreasing the incidence of restenosis in animal studies, none has yet proven successful in decreasing the incidence of restenosis in humans. Newer approaches and novel therapies are needed to prevent restenosis after percutaneous transluminal coronary angioplasty. PMID- 8213897 TI - The Costello syndrome. AB - In 1971 and again in 1977, Costello reported on two unrelated children with multiple congenital malformations associated with growth and developmental retardation and nasal papillomata (Costello, NZ Med J 74:397, 1971; Costello, Aust Paediatr J 13:114-118, 1977). Subsequently, two similar cases were described (Der Kaloustian et al., Am J Med Genet 41:69-73, 1991; Martin and Jones, Am J Med Genet 41:346-349, 1991). Costello syndrome is now a distinct entity. We describe another patient who additionally had hitherto unreported malformations, such as hydrocephalus, seizures, atrial fibrillation, and flutter with atrial septal defect. Although no nasal lesions were found he had laryngeal papillomata associated with a congenital web. A skin biopsy showed no evidence of lipid or mucopolysaccharide storage disease and muscle biopsy was normal by gross and electron microscopic examination. PMID- 8213898 TI - Further delineation of Costello syndrome. AB - We report on a 6-year-old girl with Costello syndrome. Main manifestations included poor postnatal growth, relative macrocephaly, curly hair, distinct "coarse" face, mild mental retardation, happy and sociable personality, loose dark skin particularly of hands and feet, acanthosis nigricans, thin deep set nails, enamel hypoplasia of teeth, and hyperextensible joints. The absence to date of perioral and nasal papillomata in this girl suggests that Costello syndrome is clinically recognizable even before appearance of such papillomata. Manifestations are compared to the four previously reported sporadic cases. PMID- 8213899 TI - Facio-cutaneous-skeletal syndrome is the Costello syndrome. PMID- 8213900 TI - Not a new MCA/MR syndrome but probably Costello syndrome? PMID- 8213901 TI - Costello or facio-cutaneous-skeletal syndrome? PMID- 8213902 TI - Costello syndrome and facio-cutaneous-skeletal syndrome. PMID- 8213903 TI - Costello syndrome: further clinical delineation, natural history, genetic definition, and nosology. AB - In 1977 Costello described two unrelated children with poor postnatal growth, mental retardation, curly hair, coarse face of similar appearance, and nasal papillomata, suggesting the existence of a previously undescribed syndrome of uncertain familial nature [Costello, Aust Paediatr J 13: 114-118, 1977]. The existence of this syndrome as a separate entity was substantiated several years later by two additional reports by Der Kaloustian et al. [Am J Med Genet 43:678 685, 1991] and Martin and Jones [Am J Med Genet 41:346-349, 1991]. More recently Borochowitz et al. [Am J Med Genet 43:678-685, 1992] described a new "multiple congenital anomalies/mental retardation syndrome with facio-cutaneous-skeletal involvement." Whether this condition should be considered separately from the Costello syndrome is currently a matter of debate. We present three cases, two of whom are sibs, who support the identity of the two syndromes. Our aim is to better redefine the diagnostic criteria, describe the natural history, and confirm the genetic cause of the Costello syndrome, whose pattern of inheritance is most likely autosomal recessive. PMID- 8213904 TI - Multiple meningiomas in a patient with constitutional ring chromosome 22. AB - We report on a patient with multiple congenital anomalies and ring chromosome 22 who died at age 16 years of bronchopneumonia. Autopsy documented multiple psammomatous meningiomas of the spinal dura and tentorium. Tumor tissue for cytogenetic analysis was not available. Although abnormalities of chromosome 22 in tumor tissue have been reported, to our knowledge, this is only the third report of a constitutional chromosome 22 abnormality associated with the development of meningiomas. Thus, a constitutional chromosome 22 abnormality may predispose to the development of meningiomas. PMID- 8213905 TI - Long-term follow-up of two sibs with Larsen syndrome possibly due to parental germ-line mosaicism. AB - Larsen syndrome is a heterogeneous (autosomal dominant or recessive) disorder of characteristic facial changes, multiple joint dislocations, and bone deformities. Few data on the adult presentation of the recessive form of this disorder have been reported; thus, we set out to describe two sibs thought to be affected with autosomal recessive Larsen syndrome who were evaluated as infants and later as adults. Aside from secondary joint changes and the presence of cataracts, changes described in children with autosomal recessive Larsen syndrome were noted. Three years after evaluation, the sister gave birth to a daughter with Larsen syndrome. This occurrence raises the possibility of germ-line mosaicism as the mode of inheritance in this family. Thus, germ-line mosaicism must be considered in the genetic counseling of families with Larsen syndrome in which neither parent appears affected. These patients also illustrate that despite the severe skeletal and joint deformities, the prognosis can be good with careful orthopedic management. PMID- 8213906 TI - Julia Pastrana, the nondescript: an example of congenital, generalized hypertrichosis terminalis with gingival hyperplasia. AB - Julia Pastrana (1834-1860) has gained immortality as one of the most extreme cases of generalized hypertrichosis upon record. When she was exhibited for money in the United States and Europe during the years 1855-1860, people thronged to see her, and she was several times described in the medical press of the day. After Julia Pastrana's death in childbirth, her corpse was embalmed in a very life-like manner, and exhibited all over Europe for several decades. Later, the mummy was believed to be lost, but in 1990 it was discovered at the Oslo Forensic Institute. Some writers have included Julia Pastrana among the cases of congenital hypertrichosis languinosa. However, a microscopic examination of hair samples from the mummy shows that her hairy growth is unmistakably terminal in character, and we propose that she instead was an example of congenital, generalized hypertrichosis terminalis with associated gingival hyperplasia. While many earlier writers have asserted that Julia Pastrana's dentition was abnormal, a radiographic examination of the mummy has shown that she had a complete permanent dentition. PMID- 8213907 TI - Screening for carriers of Tay-Sachs disease in the ultraorthodox Ashkenazi Jewish community in Israel. AB - A screening program for the detection of Tay-Sachs disease (TSD) carriers in the ultra Orthodox community of Ashkenazi Jews has operated in Israel since 1986. The purpose of this program is the prevention of marriages of 2 heterozygotes. The screened individuals are mostly couples in the engagement process or students in religious high schools. Two mandatory requirements guide this program. First, anonymity of the tested individuals who are identified only by code numbers; second completion of the test results of couples in the engagement process within a few days. The screening program is performed by the determination of hexosaminidase A (Hex A) activity in serum which is repeated in serum and leukocyte extracts in couples where both partners were found in the heterozygote range in the initial tests. The minimal carrier frequency was estimated to be 1:26 or higher, which is higher then in the general Jewish Ashkenazi population. This higher carrier frequency apparently stems from the fact that most members of this community originate from central Europe where the TSD carrier frequency was previously reported to be the highest in the Ashkenazi population. Since the beginning of the screening program no TSD child has been born to newlywed couples of this community in Israel. PMID- 8213908 TI - Adaptive behavior in the fragile X syndrome: profile and development. AB - In this study we present data on the adaptive behavior profile and on the development of adaptive functioning in 39 fragile X [fra(X)] males, age 4-26 years. Social adaptability is relatively well developed as compared to cognitive level and especially self-help skills continue to grow with age despite a stagnation in intellectual growth. PMID- 8213909 TI - Terminal deletion of 7q presenting in utero with a truncus arteriosus and nonimmune hydrops. AB - Terminal deletion of 7q presents with variable anatomical and developmental findings. This case is the first reported in utero diagnosis based on cytogenetic findings and in utero demonstration of resolving congestive heart failure due to a truncus arteriosus. PMID- 8213910 TI - Clarification of subtle reciprocal rearrangements using fluorescence in situ hybridization. AB - Fluorescence in situ hybridization (FISH) using chromosome-specific DNA libraries as painting probes was applied in the analysis of six subtle, balanced chromosome rearrangements. Both fresh and older slides, some of which had been previously G banded, were used to determine if FISH could identify unambiguously very small amounts of translocated material. Our results indicate that this procedure can clearly and precisely distinguish the specific components of extremely subtle translocations, in different cell types, such as leukocytes, aminocytes, and chorionic villus, and irregardless of preparation age. This ability makes FISH a valuable tool in clinical cytogenetics for the confirmation of preliminary G banded karyotypes. PMID- 8213911 TI - Combined pedigree and twin family study to determine the sources of variation in serum biotinidase activity: the usefulness of multiple study designs. AB - Biotinidase, the enzyme responsible for recycling the vitamin biotin, is deficient in most individuals with late-onset multiple carboxylase deficiency. Based on clinical criteria, biotinidase deficiency appears to be inherited as an autosomal recessive trait; however, the inheritance of biotinidase serum activity as a quantitative trait has not been studied previously. In this study, both segregation analysis of proband families and the analysis of twin family data were used to determine the relative contributions of a major gene, polygenes and environment to the variation in serum biotinidase activity. Segregation analysis of 24 families of biotinidase-deficient individuals indicated that serum biotinidase activity is determined by the segregation of a single codominant major gene with the variability about the mean of each major genotype attributable to environmental effects. Significant polygenic effects could not be detected by this analysis. Variance component analysis of 128 twin families, which included the twins, their spouses, and their offspring, indicated that 70% of total variance in biotinidase activity is attributable to additive genetic effects, 22% to individual environmental effects, and 8% to shared environmental effects. The model also included an age effect for females. A portion (27%) of the estimated additive variance may be attributed to the segregation of the major gene. This study emphasizes the usefulness of studying multiple data sets representing different types of family relationships. PMID- 8213912 TI - Pallister-Killian and Fryns syndromes: nosology. AB - Fryns syndrome is a lethal autosomal recessive multiple congenital anomaly syndrome characteristic "coarse" facies, cleft palate, diaphragmatic hernia, and distal digital hypoplasia. The appearance of the face and digits is very similar to that observed in Pallister-Killian syndrome (mosaic isochromosome 12p), although the incidence of cleft palate, diaphragmatic hernia, and neonatal death is much lower in the latter condition. We report on an infant with many manifestations of Fryns syndrome ("coarse" face, cleft palate, cloudy corneae, diaphragmatic hernia, distal digital hypoplasia, and neonatal death) who was found to be mosaic for i(12p). Her diagnosis was changed to Pallister-Killian syndrome and the family was counselled accordingly. The clinical overlap between Fryns and Pallister-Killian syndromes is discussed. Because the chromosome abnormality in Pallister-Killian syndrome is often limited to fibroblasts and may be selectively eliminated both in vivo and in vitro, some Pallister-Killian patients may be misdiagnosed with Fryns syndrome and given an erroneously high recurrence risk. Newborn infants with the Fryns or Pallister-Killian phenotypes should have chromosome studies involving multiple tissues so that the correct diagnosis can be made. This will contribute to the understanding of both disorders and facilitate appropriate genetic counselling. PMID- 8213913 TI - Joint contractures, hyperkeratosis, and severe hypoplasia of the posterior columns: a new recessive syndrome. AB - We report on 2 brothers with arthrogryposis, hyperkeratosis, and severe hypoplasia of dorsal roots and posterior columns in the one sib who was examined at autopsy. This appears to represent a new arthrogryposis syndrome with poor prognosis, most likely inherited as a single gene, either autosomal or X-linked recessive trait. PMID- 8213914 TI - Galloway-Mowat syndrome of abnormal gyral patterns and glomerulopathy. AB - The combination of microcephaly, gyral abnormalities, developmental delay, and a glomerulopathy constitutes a recognizable syndrome. The inheritance is autosomal recessive. Additional abnormalities may include seizures, minor facial anomalies, and hiatal hernia. Onset of proteinuria often occurs in the first 3 months of life, but always before age 3 years. A uniform pattern of renal histologic changes has not been found. There is no effective treatment for the neurologic or renal manifestations of this condition. The prognosis is extremely poor; every patient but one has died before age 5 1/2 years. Antenatal diagnosis may be possible. PMID- 8213915 TI - Possible association between the hernia of Morgagni and trisomy 21. AB - Of the 5 liveborn infants with the hernia of Morgagni recorded in the California Birth Defects Monitoring Program, 3 had trisomy 21. This significant association (P < 10(-6)) between the hernia of Morgagni and trisomy 21 may reflect defective dorsoventral migration of rhabdomyoblasts from the paraxial myotomes, caused by increased cellular adhesiveness in trisomy 21. PMID- 8213916 TI - Whose DNA is it anyway? Relationships between families and researchers. AB - DNA obtained for research may, at a later time, become crucial for carrier and prenatal diagnosis. Continuing rapid advances in human genetics make this scenario more and more common. The following case illustrates some of the problems that may occur when DNA donors and researchers do not establish a verbal or written agreement at the time the DNA is obtained. The legal and ethical ramifications of this situation are examined through case discussion and review of the literature. We propose that even in the absence of a verbal or written agreement, researchers continue to have a responsibility to share any significant information obtained from linkage studies with donor families if such information becomes available. If the DNA specimens become critical for prenatal or carrier testing at a later time, we feel that the family has a right to request and receive aliquots of such specimens. The research unit should have the right to charge a storage fee for DNA banking. Clear agreement between donor and researcher at the time of specimen collection may avoid legal and ethical problems in the future. PMID- 8213917 TI - Gerodermia osteodysplastica: report on two patients and surgical correction of facial deformity. AB - We present four individuals with Gerodermia Osteodysplastica in a Jewish family from Morocco confirming the autosomal recessive inheritance of the disorder. Three previously unreported findings are described: a) enlarged funnel-shaped mandibular lingula; b) extension of the mandibular premolar and molar roots below the inferior dental canal, and of the second molars into the lower border of mandibular cortical bone; and c) hypercementosis of the maxillary incisors and mandibular molars surrounded by a radiolucent halo in several teeth. The facial deformity resulting from maxillary hypoplasia and mandibular prognathism was corrected by orthognathic surgery: Le Fort I maxillary osteotomy and vertical mandibular osteotomy. PMID- 8213918 TI - Hereditary nodular heterotopia accompanied by mega cisterna magna. AB - This is the first report of hereditary nodular heterotopia accompanied by mega cisterna magna. Magnetic resonance imaging documented multiple bilateral subependymal nodules, which were isointense to gray matter. This disease entity is considered a dominant trait, since the mother and two daughters, half-sisters, were affected. PMID- 8213919 TI - Hydrops-ectopic calcification-moth-eaten skeletal dysplasia (Greenberg dysplasia): prenatal diagnosis and further delineation of a rare genetic disorder. AB - An offspring of consanguineous parents of East-Indian origin was found prenatally to have hydrops fetalis, short limb dwarfism, polydactyly and chondro-osseous changes consistent with Greenberg hydrops-ectopic calcification-moth-eaten skeletal dysplasia (HEM) dysplasia. The radiological changes include platyspondyly with multiple extra ossification centers, extraneous calcification in the ribs, sternum, pelvis, and epiphysis, and moth-eaten long bones. The histopathological changes included chondrocytes with dilated rough endoplasmic reticulum and inclusion bodies with homogeneous material of intermediate electron density. These findings further delineate the spectrum of this rare autosomal recessive skeletal dysplasia. PMID- 8213920 TI - Newly recognized autosomal recessive MCA/MR/overgrowth syndrome. AB - We report on two sibs, born to nonconsanguineous parents, presenting with mental retardation, overgrowth, craniosynostosis, distal arthrogryposis, sacral dimple, and joint laxity. These patients may have a previously undescribed autosomal recessive syndrome. PMID- 8213921 TI - Carpenter syndrome with normal intelligence: Brazilian girl born to consanguineous parents. AB - We report on a Brazilian girl with Carpenter syndrome born to consanguineous parents. She had normal neuropsychological development, postnatal overgrowth, and oligodontia of the permanent teeth. Clinical and genetic aspects are discussed. PMID- 8213922 TI - Mobius sequence: further in vivo support for the subclavian artery supply disruption sequence. AB - Mobius sequence consists of a congenital bilateral facial nerve palsy and external ophthalmoplegia often associated with malformations of the limbs and orofacial structures. The pathogenesis of the sequence is a subject of debate. However, a new hypothesis proposes that Mobius sequence results from an interruption of embryonic blood supply (subclavian artery supply disruption sequence). Here we present an infant with bilateral facial nerve palsy (VII), external ophthalmoplegia (IV, VI), paresis of cranial nerves V, IX, X, XI, and XII, absence of the pectoralis major muscle (Poland anomaly), terminal transverse limb defects, and absence of the right diaphragm. Also, he was found to have discrete foci of brainstem calcifications in the region of the dorsal respiratory group on both CT scan and the histologic sections with microscopic evidence of diffuse brainstem "injury." The anomalies and histopathology noted in this infant imply that vascular insufficiency prior to the sixth week of gestation involving the proximal sixth intersegmental artery may result in the manifestations presented in this report and lend further support for the existence of a subclavian artery supply disruption sequence. PMID- 8213923 TI - Variable clinical expression of mosaic trisomy 16 in the newborn infant. AB - Trisomy 16 is common in embryos and fetuses aborted early during development. Mosaicism for trisomy 16 is sometimes encountered during prenatal diagnosis, particularly with chorionic villi biopsy specimens, and, until recently, was thought to be confined to the placenta. However, recently, several liveborn infants with trisomy 16 mosaicism have been described. We report on an additional liveborn infant with trisomy 16 mosaicism and compare the clinical findings with those of the previously reported cases in an attempt to delineate a mosaic trisomy 16 syndrome. Cytogenetic analysis from our patient showed that there was a different proportion of abnormal cells in different tissues and that the anomaly was undetectable in blood lymphocyte cultures. This observation was consistent with some of the previous reports. DNA analysis of parents and child was carried out using a polymorphic dinucleotide marker that maps to the long arm of chromosome 16. This analysis showed that the extra chromosome 16 in the infant was maternal in origin and suggested that the nondisjunction was probably a first meiotic division error. Our results suggest that an investigation of multiple tissues is required before concluding that mosaicism is confined to the placenta. We conclude that a finding of trisomy 16 mosaicism at prenatal diagnosis should be regarded with extreme caution. This diagnosis may be associated with a highly variable phenotype that may occasionally be compatible with extrauterine life. PMID- 8213924 TI - Two siblings with midline field defects and Hirschsprung disease: variable expression of Toriello-Carey or new syndrome? AB - We describe 2 sibs with multiple congenital anomalies. The main manifestations include hypoplasia of the corpus callosum and/or cerebellar hypoplasia, Robin sequence, pharyngeal and laryngeal hypoplasia, abnormal ears, excessive neck skin, cardiac defect, and Hirschsprung disease. The presence in 2 sibs born to healthy, consanguineous parents suggests autosomal recessive inheritance. These anomalies must have arisen during blastogenesis; the syndrome resembles most the condition described in 1988 by Toriello and Carey. PMID- 8213925 TI - Neonatal proteus syndrome. PMID- 8213926 TI - Oral-facial-digital syndrome and retinal abnormalities with autosomal recessive inheritance. PMID- 8213927 TI - Oxygen administration increases plasma digoxin-like substance and renal sodium excretion in chronic hypoxic patients. AB - Despite the absence of cardiac or renal pathologies, edema and mild hyponatremia may often occur in patients affected by chronic obstructive pulmonary disease (COPD). Therefore, it has been suggested that hypoxia may influence the release of different hormones regulating renal sodium handling. To evaluate the effect of hyperoxia and O2 removal on plasma digitalis-like substance (DLS) levels, 9 patients affected by COPD and 7 normal subjects were studied. After 1 h in supine position, O2 was administered for 3 h by a tight-fitting face-mask. Blood samples for plasma DLS were taken at time 0, 60, 180 min and then for 3 h after O2 removal. In normal subjects, plasma DLS did not vary after O2 administration (from basal values of 162.25 +/- 8.59 to 107.75 +/- 6.65 pg/ml at 180 min; NS), and O2 removal (143.7 +/- 16.87 pg/ml after 3 h from O2 removal; NS). On the contrary, in patients affected by COPD, plasma DLS levels increased during O2 administration (from basal values of 138.98 +/- 8.31 to 202.14 +/- 8.21 pg/ml at 180 min; p < 0.05), and returned to baseline levels (142.59 +/- 8.28 pg/ml) 3 h after O2 removal. In the same patients, DLS increase was accompanied by a rise in Na+ excretion (from 0.08 +/- 0.01 at time 0 to 0.16 +/- 0.02 mEq/min after 3 h of O2 administration; p < 0.05). In conclusion, our findings showed an oxygen related increase in plasma DLS levels and in urinary Na+ excretion in patients affected by COPD. This phenomenon could promote Na+ urinary loss during prolonged O2 therapy in these patients and should be taken into account in their management. PMID- 8213928 TI - Morphometric study showing the importance of distal tubular damage in impaired creatinine clearance. AB - It is established that the glomerular filtration rate (GFR) is affected by tubulointerstitial lesions (TIL) in various glomerulonephritides. The fall in GFR is believed to be the result of damage to tubules, mainly the proximal tubules, and interstitial widening. We performed the morphometric point-counting study in 45 renal biopsies with various glomerular diseases, and 10 controls, to quantify interstitial widening, proximal and distal tubular damage, and to study their relation to serum creatinine clearance, and also to determine the best predictor, and the degree of damage in each component of the tubulointerstitium. There was a statistically significant correlation of serum creatinine clearance to interstitial widening (r = -0.748; p = 0.0001) and decrease in proximal (r = 0.611; p = 0.0001) and distal tubular area percentages, with a maximum value of the correlation coefficient for the distal tubules (r = 0.818; p = 0.0001). On the basis of relative mean difference values, it appeared that in the presence of tubulointerstitial damage, the distal tubule sustained greater damage. Therefore, distal tubular damage may serve as an important prognostic parameter. PMID- 8213929 TI - Effect of dietary manipulations on glomerular filtration rate of mice offspring of nephrectomized mothers. AB - We have previously reported that mice, offspring to uninephrectomized mothers, have greater than normal kidneys with supernumerary glomeruli. In this study we assessed glomerular filtration rate (GFR) in 40 mice offspring of nephrectomized mothers and 40 mice offspring of sham-nephrectomized animals aged 7 weeks. Each group was divided into 4 equal subgroups according to the following dietary manipulations: regular, high protein, high salt and high protein/high salt. At the end of 1 week, GFR was determined by 51Cr EDTA. In the first group, GFR was significantly greater in each experimental subgroup compared to control. In the offspring of sham-nephrectomized mothers, only the subgroup on the combined diet had a significantly greater GFR. We conclude that the capacity to raise GFR in response to dietary manipulations is greater in offspring of nephrectomized mothers. It remains to be elucidated whether the difference results from the increased number of nephrons or from an augmented single nephron GFR reserve. PMID- 8213930 TI - Relationship of the recovery in the glomerular filtration rate to the duration of anuria in diarrhea-associated hemolytic uremic syndrome. AB - The relationship of the duration of anuria to the recovery in glomerular filtration rate (GFR) was studied in 71 children with diarrhea-associated hemolytic uremic syndrome. A significant relationship was found, and regression analysis revealed that y = 114.61 - 5.68 x, where y is predicted GFR (ml/min/1.73 m2) and x is the square root of the duration of anuria in days. The presence of hypertension or proteinuria on follow-up was significantly related to the duration of anuria (p = 0.005 and p = 0.002, respectively). PMID- 8213931 TI - Blood lead in hemodialysis patients. AB - Blood lead corrected for hematocrit (PbC) was measured in 115 hemodialysis (HD) patients. Information was collected with a questionnaire about personal and environmental factors thought to influence blood Pb levels. HD patients had significantly higher mean blood Pb than healthy subjects (p < 0.001). A non negligible percentage of the HD population (13%) had values over 30 micrograms/dl, the threshold for risk in occupational exposure, and 4% over 40 micrograms/dl which reflects Pb intoxication. No association was found between sex, age, duration of HD and PbC. The prevalence of high diastolic blood pressure was associated with PbC over 30 micrograms/dl (p < 0.01). Also, at blood Pb levels generally considered as 'nontoxic' (less than 40 micrograms/dl), we found a low correlation with diastolic blood pressure (r = 0.19, p = 0.049). A correlation was found between PbC and parathyroid hormone (r = 0.22, p = 0.01) and between PbC and mean corpuscular volume (r = -0.21, p = 0.02). The patients with individual risk factors (smoke, alcohol consumption and alkyl Pb from air contamination) had PbC levels higher than patients without (p = 0.001). The patients with environmental risk factors (professional exposure, tap water consumption and older houses) had PbC levels higher than patients without (p = 0.01). Patients with past occupational exposure had the highest mean PbC levels (34.1 micrograms/dl = 1.65 nM/ml). PMID- 8213932 TI - Scintigraphic evaluation of functional renal reserve using angiotensin-converting enzyme inhibition in patients with type II diabetes mellitus. AB - Acute effects of 20 mg oral enalapril (E), and angiotensin-converting enzyme inhibitor, on renal function and the renin-angiotensin-aldosterone system were investigated in 13 patients with type II diabetes mellitus (8 female, 5 male) and 10 hypertensive controls using a radionuclide method. Plasma glucose control was evaluated with fructosamine (F) determinations. After intravenous administration of 370 MBq 99mTc-DTPA, sequential images were recorded. Glomerular filtration rate (GFR), perfusion index (PI), time to maximum activity and reno index values of the kidneys were calculated. Two days later, renal scintigraphy was repeated after oral administration of E. Plasma levels of renin, angiotensin II and aldosterone were analyzed using RIA. Basal GFR values (mean: 92.6 ml/min) correlated with F (r = 0.364; p < 0.05). In the diabetic group, 5 patients had a decrease in GFR and an increase in PI after oral E. The mean percent change of GFR was 12 +/- 32 for patients and 20 +/- 12 for controls, respectively. Percent change of GFR had a slightly negative correlation with F values (r = -0.51; p < 0.05) and with PI (r = -0.65; p < 0.001). The patients with good metabolic control had an increase in GFR and a decrease in PI indicating an increase in renal blood flow and glomerular filtration. In patients with proteinuria and poorly controlled diabetes, in response to E-induced efferent arteriolar dilation, there is a decrease in GFR and an increase in PI which indicates a fall in filtration and renal blood flow. This glomerular hemodynamic pathology precedes morphological changes due to diabetes. PMID- 8213933 TI - Parathyroid hormone-parathyroid hormone related protein receptor messenger RNA is present in many tissues besides the kidney. AB - Parathyroid hormone (PTH) acts on a large number of cells derived from many different tissues that are not traditional targets (kidney and bone) for their action. Also, the acute exposure of many of these cells to PTH resulted in the generation of cAMP. These observations are consistent with the presence of PTH receptors on these cells. However, there is no evidence that the cells that are not traditional targets for PTH, express the receptor of the hormone. The cloning of the PTH-PTH related protein (PTH-PTHrP) receptor provided the tool to examine whether these cells contain the mRNA for this receptor. Poly A+RNA from a variety of rat tissues was probed with a 1,200-bp fragment of the cDNA of the PTH-PTHrP receptor by the Northern blot technique. We found that mRNA for the PTH-PTHrP receptor is present in the heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis. Transcripts of 2.4 kb were found in all these tissues with the strongest expression in the kidney. In addition, smaller RNAs were detected in the kidney (approximately 1.8 kb) and testis (1.5 kb). These results indicate that many cell types express the PTH-PTHrP receptor gene. The data provide a possible explanation for the direct effects of PTH on so many cells and for the understanding of the harmful effects of chronic excess of PTH on the function of many organs in chronic renal failure. PMID- 8213934 TI - Iodine-131 treatment of hyperthyroidism in a patient on dialysis for chronic renal failure. AB - A 7- to 8-cm diffuse toxic goiter with associated symptoms of hyperthyroidism developed in a 38-year-old black female undergoing regular hemodialysis for renal failure. Our treatment of choice was an ablative dose of radioactive iodine in the form of sodium iodide (Na-131I). To our knowledge, this is only the 4th documented case of hyperthyroidism in a patient with renal failure. Detailed monitoring of 131I radioactivity in the blood, thyroid gland and the dialysate demonstrated that there was no radiation hazard to personnel involved in the patient management. PMID- 8213935 TI - Rapidly progressive glomerulonephritis associated with bacterial endocarditis: efficacy of antibiotic therapy alone. AB - A 65-year-old woman presented rapidly progressive glomerulonephritis with purpura and mitral insufficiency. Blood cultures grew Streptococcus mitis. By light microscopy, the renal biopsy revealed necrotizing glomerulonephritis 56% associated with cellular crescents and tubulointerstitial changes. By immunofluorescence, deposits of IgM and C3 were found to be present in the mesangium. Electron-microscopic study showed subendothelial and intramembranous deposits. Treatment with antibiotics alone resulted in renal recovery with disappearance of proteinuria, circulating immune complexes and cryoglobulinemia. A 2nd renal biopsy, performed after 3 months, showed segmental sclerosis and tubulointerstitial lesions. Eight months after the first hospitalization, cardiac insufficiency occurred. Four years later, a valve replacement was performed. No abnormal serum creatinine, serum creatinine clearance or urinalysis levels were present. These data suggest that rapidly progressive glomerulonephritis associated with bacterial endocarditis may be treated by antibiotics alone and result in normal and stable renal function. PMID- 8213936 TI - Marcello Malpighi. 1628-1694. PMID- 8213937 TI - Check that methotrexate dose. PMID- 8213938 TI - Watch out for misleading chemical names. PMID- 8213939 TI - Dialysis considerations. PMID- 8213940 TI - Dialysis considerations. PMID- 8213941 TI - Marjorie. PMID- 8213942 TI - Orchestrating the care of mechanically ventilated patients. PMID- 8213943 TI - How to keep adrenal insufficiency in check. PMID- 8213944 TI - The gentle art of nurturing yourself. PMID- 8213945 TI - 9 common i.v. complications and what to do about them. PMID- 8213946 TI - Managing isolated systolic hypertension. PMID- 8213947 TI - Subdural hematoma. PMID- 8213948 TI - Recognizing, treating, and preventing lead poisoning. PMID- 8213949 TI - Evaluating arterial blood gas syringes. PMID- 8213950 TI - No more locked doors. PMID- 8213951 TI - Discover the healing power of books. PMID- 8213952 TI - Needlesticks and spatter to the face and eyes. PMID- 8213953 TI - Two years of exposure to Cytovene. PMID- 8213954 TI - To the mother I never met. PMID- 8213955 TI - Carbon dioxide cautions. PMID- 8213956 TI - Prayer is a nursing intervention. PMID- 8213957 TI - Let them see the scars. PMID- 8213958 TI - My neighbor, my patient. PMID- 8213959 TI - What you should know about thrombolytic therapy for acute MI. PMID- 8213960 TI - When the physician won't give up. PMID- 8213961 TI - Unconventional PCA: making it work for your patient. PMID- 8213962 TI - TB skin testing: how to do it right. PMID- 8213963 TI - From expert to novice. PMID- 8213964 TI - Street-smart advice on treating drug overdoses. PMID- 8213965 TI - Defining moment. PMID- 8213966 TI - Christopher's art. PMID- 8213967 TI - For refusing to treat an AIDS patient. PMID- 8213968 TI - Role of the vitreous in the prognosis of peripheral uveitis. AB - We studied 116 eyes with peripheral uveitis (mean follow-up, 5.0 years) to ascertain the effect of the vitreous on prognosis. At the initial examination, the prevalence of partial posterior vitreous detachment was significantly higher in eyes with macular edema (27%) than in those without (7%, P = .01). During follow-up, the prevalence of no posterior vitreous detachment initially was significantly higher in eyes that developed macular edema (78%) than in those that did not (22%, P = .01). The prevalence of no or partial posterior vitreous detachment was also significantly higher in eyes with decreased visual acuity of three or more Snellen lines (57% and 38%, respectively) compared with those with visual acuity decreases of two Snellen lines or less (21% and 11%; P = .02 and P = .01, respectively). Eyes with peripheral uveitis with vitreous adhesion may have a less favorable prognosis compared with those with complete posterior vitreous detachment. PMID- 8213969 TI - Behcet's disease associated with one of the HLA-B51 subantigens, HLA-B* 5101. AB - The strong association of Behcet's disease with HLA-B51 in several ethnic groups is well known. Because the HLA-B51 antigen has been recently identified to comprise three alleles, HLA-B* 5101, HLA-B* 5102, and HLA-B* 5103, we sought to investigate whether there is any correlation of one particular allele among them with B51-positive patients with Behcet's disease. Forty-six Japanese patients with Behcet's disease and HLA-B51 were typed by using the alloantisera, which allowed the subdivision of B51 antigen by the microlymphocyte toxicity assay. All the patients were found to carry HLA-B* 5101. This result suggests that amino acid substitutions at residue 167 or 171 prevent the development of Behcet's disease, because HLA-B* 5101 differs from HLA-B* 5102 and HLA-B* 5103 by single amino acid substitution at residues 171 and 167, respectively, or that another non-HLA gene tightly linked to the HLA-B* 5101-associated haplotype around the HLA class I gene region is responsible for the susceptibility to Bechcet's disease. This study provides insight into the molecular mechanism underlying an HLA association with Behcet's disease. PMID- 8213970 TI - Membranoproliferative glomerulonephritis type II associated with central serous retinopathy. AB - Membranoproliferative glomerulonephritis type II is specifically associated with the presence of dense deposits in the basement membrane of Bruch's membrane, which result in lesions similar to basal laminar drusen, exudative drusen, and retinal pigment epithelial detachments. In advanced stages of this dense-deposit retinopathy, choroidal neovascularization may occur. We observed a 36-year-old patient with membranoproliferative glomerulonephritis type II who developed central serous retinopathy in the presence of specific dense-deposit-associated fundus lesions. The diffuse drusenlike dense deposits (at the level of Bruch's membrane) and associated retinal pigment epithelial detachments appear to contribute to the pathogenesis of central serous retinopathy. Thus changes in Bruch's membrane may be involved in the development of central serous retinopathy. PMID- 8213971 TI - Paresis of a vertical rectus muscle after cataract extraction. AB - Nine patients had a permanent paresis of a vertical rectus muscle after cataract extraction. We sought to determine the common factors associated with and their contribution to vertical muscle paresis after cataract extraction. The study design included a survey that was conducted among the referring cataract surgeons and anesthesiologists with particular attention to surgical technique and anesthetic administered, as well as a medical history and examination and appropriate laboratory tests. Patients had a complete ophthalmic examination including prism cover testing in all nine diagnostic positions, forced-duction testing, and saccadic velocity and generated muscle force estimation. The results of the study demonstrate no correlation between the pareses and the use of a bridle suture, antibiotic or corticosteroid injection, systemic disease, or surgical technique. Peribulbar anesthesia was the most consistent feature in seven of the nine cases. In the other two, an atypical retrobulbar injection had been given. On the basis of the location of the injections, the needle type, and the concentration and quantity of the anesthetic injected, we conclude that permanent pareses of a vertical rectus muscle may be caused by a myotoxic effect of the local anesthetic. PMID- 8213972 TI - Depth of anisometropic amblyopia and difference in refraction. AB - Disagreement exists as to whether the depth of anisometropic amblyopia correlates with the degree of anisometropia. We reviewed the charts of 303 consecutive patients with the diagnosis of amblyopia. Thirty-five patients with untreated anisometropia without strabismus were identified. The best-corrected visual acuities, manifest refractions, and autorefractions were recorded. The differences in spherical equivalent, root mean square, and an index of anisometropia, which we defined, were calculated. The depth of amblyopia was strongly correlated to all three measures of anisometropia for both hyperopic and myopic individuals. Our new index of anisometropia was an excellent predictor of the depth of amblyopia. PMID- 8213973 TI - The visual-evoked response in infants with central visual impairment. AB - We studied ten children with central visual impairment with a known neurologic defect and an abnormal visual-evoked response who had results of repeat electrophysiologic testing evaluated at the Children's Hospital of Philadelphia from December 1989 through July 1991. Central visual impairment is defined as poor visual function with a normal anterior visual pathway. Age at first examination ranged from 5 to 48 months with a followup of two to 31 months. Repeat visual-evoked response testing showed improvement in seven patients and no change in three. Grating acuity as measured by the Teller acuity card procedure, performed in nine of ten patients, improved in seven, showed no change in one, and declined in one. We found a potentially favorable prognosis for those infants with central visual impairment, despite an initially abnormal visual-evoked response. We used a clinical approach to this disorder to improve diagnostic categorization and prognostic capabilities in central visual impairment. PMID- 8213974 TI - Diode-laser photocoagulation for zone 1 threshold retinopathy of prematurity. AB - We used the diode-laser indirect ophthalmoscope in the treatment of 17 (30 eyes) infants with zone 1 (a circle centered on the optic disk with a radius of twice the distance from the disk to the fovea) threshold retinopathy of prematurity (at least five continuous or eight cumulative 30-degree sectors [clock hours] of ridge with extraretinal fibrovascular proliferation in the presence of plus disease). Mean follow-up was 31.2 weeks. Two eyes (6.7%) required retreatment of missed areas that had persistent plus disease (enlarged posterior veins and tortuous arterioles). A favorable outcome was attained in 25 eyes (83.3%). Five eyes (16.7%) developed retinal detachments, three of which remained stable at Stage 4A (extrafoveal retinal detachment) and two of which ultimately progressed to Stage 5 (total retinal detachment). Both eyes that went on to Stage 5 had severe posterior pole hemorrhages at the time of treatment. Two eyes that developed retinal detachments (one, stage 4A and one, stage 5) had rhegmatogenous components. Among 14 infants followed up for more than three months, four developed nystagmus, and six developed strabismus. In contrast to cryoablation, diode-laser photoablation of the peripheral retina was found to be an effective treatment for threshold retinopathy of prematurity located in zone 1. Portability and ease of use of the laser system, precision of treatment, and minimal postprocedural adnexal inflammation are further advantages of this therapeutic modality. PMID- 8213975 TI - Corneal allograft rejection after multiple blood transfusions. AB - We treated two patients with corneal allograft rejections, both of which occurred within a few weeks after administration of multiple blood transfusions. In the first case, a patient with a graft that had been previously clear for 11 years developed severe endothelial rejection six weeks after transfusion of ten units of packed red blood cells. In the second case, a graft that had been clear for 14 months irreversibly rejected two weeks after transfusion of six units of packed red blood cells. These cases suggest that multiple blood transfusions may be a risk factor for corneal allograft rejection. PMID- 8213976 TI - Conjunctival epithelial cell hypermitosis and goblet cell hyperplasia in atopic keratoconjunctivitis. AB - Atopic diseases that include eczema (atopic dermatitis), asthma, and seasonal and perennial rhinoconjunctivitis are common manifestations of abnormal immediate hypersensitivity. Ocular involvement, such as atopic keratoconjunctivitis, characteristically includes conjunctival and corneal inflammation, and in a severe form, conjunctival scarring, symblepharon, corneal epitheliopathy, and visual loss. To examine the conjunctival cellular abnormalities in atopic keratoconjunctivitis, we studied the in vivo differentiation and tissue-culture growth characteristics of conjunctiva from normal subjects and patients with severe atopic keratoconjunctivitis. We examined conjunctival biopsy specimens to determine epithelial mitotic rate and goblet cell frequency, and we studied conjunctival explants to determine the latent period for fibroblast outgrowth and fibroblast doubling time. The mitotic rate for atopic keratoconjunctivitis, 6.7% +/- 2.1% (11 patients), was statistically significantly greater than for normal subjects, 2.0% +/- 0.63% (seven subjects) (P = .05). Also the goblet cell frequency for atopic keratoconjunctivitis, 14.6% +/- 3.4% (11 patients), was statistically significantly greater than for normal subjects, 4.8% +/- 0.92% (seven subjects) (P = .02). The latent period for fibroblast outgrowth and the fibroblast doubling time for atopic keratoconjunctivitis were not statistically significantly different from normal control subjects. Therefore, atopic keratoconjunctivitis was associated with conjunctival epithelial hypermitosis, goblet cell hyperplasia, and normal fibroblast tissue-culture growth. These characteristics may be useful in the diagnosis of atopic keratoconjunctivitis. We previously studied another disease characterized by chronic conjunctival inflammation and scarring, cicatricial pemphigoid, which also demonstrated conjunctival epithelial hypermitosis, but in contrast there was near absence of goblet cells, and the fibroblasts were hyperproliferative. These differences may be used to distinguish atopic keratoconjunctivitis from cicatricial pemphigoid. PMID- 8213977 TI - A prospective, randomized comparison of thermal cautery and argon laser for permanent punctal occlusion. AB - Permanent punctal occlusion was performed by two techniques on 27 patients (73 puncta). Patients were randomly assigned to be treated with either thermal cautery or argon laser for keratitis sicca. Follow-up assessment disclosed that the puncta to which thermal cautery was applied remained closed significantly longer than those to which laser treatment was applied (P < .05, log-rank test). Using time to recanalization of a punctum as the end point, we found a long-term advantage of thermal cautery over argon laser treatment. PMID- 8213978 TI - Optic nerve sheath decompression for visual loss in patients with acquired immunodeficiency syndrome and cryptococcal meningitis with papilledema. AB - Visual dysfunction developing in association with acquired immunodeficiency syndrome (AIDS) can be multifactorial. Two patients with this syndrome and cryptococcal meningitis had papilledema and visual loss. Both were treated by optic nerve sheath fenestration. One patient had bilateral nonsimultaneous optic nerve sheath fenestrations; visual function improved in one eye. The other patient had bilateral visual improvement after a unilateral optic nerve sheath fenestration. Cryptococcal organisms were present in the dural sheath specimens of both patients despite ongoing therapy with antifungal medication. Postoperative orbital infectious complications did not occur. Autopsy examination of one patient showed that the sites of fenestration were patent. Medical treatment of cryptococcal meningitis associated with AIDS has a guarded prognosis. Optic nerve sheath fenestration offers a treatment alternative for papilledema and visual loss that occur with cryptococcal meningitis. PMID- 8213979 TI - Reproducibility of postural changes in intraocular pressure with the Tono-Pen and Pulsair tonometers. AB - Reproducibility of measurements of postural changes in intraocular pressure was determined by using the Tono-Pen (Mentor O & O, Inc., Norwell, Massachusetts) and Pulsair (Keeler Instruments, Inc., Broomhall, Pennsylvania) tonometers. Thirty subjects had three repeated sitting and reclining measurements performed on three separate visit days. Reproducibility coefficients of 3.3% for the Tono-Pen and 6.3% for the Pulsair were obtained for the within-visit postural change measurements. Across-visit reproducibility coefficients were 7.9% and 26.2% for the Tono-Pen and Pulsair, respectively. The estimated standard deviations for both the within-visit and across-visit postural change measurements were high for both instruments. These results indicate poor reproducibility of measurements of postural changes in intraocular pressure. PMID- 8213980 TI - Stereoscopic photography with a scanning laser ophthalmoscope. AB - Digital fundus angiography has advantages over conventional photography. However, digital angiography as it is normally performed, provides no stereoscopic information. Because stereoscopic data can be crucial in the evaluation of conditions such as age-related macular degeneration, we developed methods to record stereoscopic information during video angiography with a scanning laser ophthalmoscope and to produce high-quality static stereoscopic images. Stereoscopic information was collected by moving the scanning laser ophthalmoscope side-to-side and with a modified Allen separator. Stereoscopic images were displayed as stereoscopic pairs on 35-mm film, stereoscopic pairs from a digital printer, and as stereoscopic images directly on a conventional video monitor. This system to capture and display stereoscopic information is convenient, uses readily available technology, and can be adapted to any digital angiography system. PMID- 8213981 TI - The retinal irradiance and spectral properties of the multiport illumination system for vitreous surgery. AB - The multiport illumination system was developed as a fiberoptically illuminated pars plana cannula system for vitreous surgery. The retinal irradiance of the multiport illumination system and several other commonly used endoilluminators (light pipes) measured at 5 mm are comparable, ranging from 94 to 256 mW/cm2. In the actual surgical setting, however, the retinal irradiance of the multiport illumination system is far less (56 mW/cm2) because the end of the fiberoptic cables are fixated in the pars plana 16.5 mm away from the retinal surface. A reduction in the maximal intensity (100%) to 50% reduces the retinal irradiance by approximately two thirds to 3.7 mW/cm2. The light emitted by the multiport illumination system used in conjunction with a long-wave pass filter with a cutoff wavelength of 420 nm reduces the amount of short-wavelength light by one third to about 4% of the overall irradiance. PMID- 8213982 TI - Potential retinal phototoxicity. PMID- 8213983 TI - Conjunctival Kaposi's sarcoma treated with interferon alpha-2a. PMID- 8213984 TI - Optisol containing streptomycin. PMID- 8213985 TI - Propionibacterium acnes endophthalmitis after Staphylococcus epidermidis endophthalmitis. PMID- 8213986 TI - Subconjunctival miconazole and anterior segment blastomycosis. PMID- 8213987 TI - Intraocular lymphoma after liver transplantation. PMID- 8213988 TI - Ocular and orbital toxicity after intracarotid cisplatin therapy. PMID- 8213989 TI - Cysticercosis as a cause of severe medial rectus muscle myositis. PMID- 8213990 TI - A glass micropipette holder for ophthalmic surgical procedures. PMID- 8213991 TI - Vitreous photography with a wide-angle preset slit-lamp lens. PMID- 8213992 TI - Late detachment of Descemet's membrane after subconjunctival THC:YAG (holmium) laser thermal sclerostomy ab externo. PMID- 8213993 TI - Effect of insulin therapy on progression of retinopathy in noninsulin-dependent diabetes mellitus. PMID- 8213994 TI - Another reevaluation of combined cataract and glaucoma surgery. PMID- 8213995 TI - Expression of osteopontin messenger RNA by macrophages in atherosclerotic plaques. A possible association with calcification. AB - Calcification is a common complication in atherosclerosis. As osteopontin (OPN) and osteonectin (ON) are not only involved in the physiological but also the pathological calcification of tissues, we examined the expression of OPN and ON messenger (m)RNAs in normal and atherosclerotic human aortas. By Northern blotting, the OPN mRNA expression was related to the severity of the atherosclerosis. However, ON mRNA expression decreased with the development of atherosclerosis. By a combination of in situ hybridization and immunohistochemistry of serial sections, the macrophages surrounding the atheromatous plaques were identified as the OPN mRNA-expressing cells. The ON mRNA-expressing cells in aortas of a newborn baby and a 3-year-old boy were medial smooth muscle cells, but in aortas of adults, smooth muscle cells that had invaded the intima were found to express ON mRNA. As OPN mRNA-expressing macrophages surrounded the atheromatous plaques, and as the level of OPN mRNA expression increased as atherosclerosis advanced, it is possible that OPN plays a role in the calcification of atheromatous plaques. PMID- 8213996 TI - Polymorphonuclear leukocytes as a significant source of tumor necrosis factor alpha in endotoxin-challenged lung tissue. AB - The kinetic expression and potential cellular source of tumor necrosis factor alpha (TNF-alpha) in lipopolysaccharide-(LPS) induced acute lung inflammation was investigated using a rat model by Northern blot analysis, in situ hybridization and immunohistochemistry. LPS induced a polymorphonuclear leukocyte infiltrate in the lung that peaked between 6 and 24 hours. TNF-alpha messenger (m)RNA was strongly induced by LPS in whole lung tissues shown by Northern analysis. Both alveolar macrophages and polymorphonuclear leukocytes (PMNs), purified from bronchoalveolar lavage fluids of LPS-treated rats, were shown to express TNF alpha mRNA by Northern analysis. However, PMNs displayed several times more TNF alpha mRNA, relative to actin mRNA, than alveolar macrophages at 6 and 12 hours. By in situ hybridization, most of the cells positive for TNF-alpha mRNA at 6 and 12 hours seemed to be PMNs located within the tissue near bronchioles or vessels. By immunohistochemistry, TNF-alpha protein was localized mainly to alveolar macrophages at early times (1 to 3 hours) after LPS challenge, and thereafter, PMNs seemed to be the predominant source of TNF-alpha protein as more than 90% of total intraalveolar positive cells at 6 and 12 hours were PMN. Thus, our data provide the first in vivo evidence that PMNs can serve as a significant source of TNF-alpha at sites of acute inflammation. PMID- 8213997 TI - Interferon-gamma and tumor necrosis factor-alpha exert their antirickettsial effect via induction of synthesis of nitric oxide. AB - How the host defenses control rickettsiae in the cytosol of nonphagocytic host cells, where they are not exposed to antibodies or phagocytes, has posed a difficult question. Rickettsia conorii infection of a mouse fibroblast cell line was inhibited in a dose-dependent manner by nitrogen oxide synthesized by eukaryotic host cells stimulated by interferon-gamma or tumor necrosis factor alpha. L-arginine was the source of the nitric oxide as demonstrated by competitive inhibition by NG-monomethyl-L-arginine. Nitric oxide synthesis required host cell protein synthesis and had an approximately 48-hour lag phase following cytokine stimulation. At low doses of interferon-gamma and tumor necrosis factor-alpha, which had no detectable response as single agents, dramatic synergistic nitric oxide synthesis and antirickettsial effects were observed. PMID- 8213998 TI - Basic fibroblast growth factor: its role in the control of smooth muscle cell migration. AB - The formation of an intimal lesion in an injured artery is the consequence of the replication and migration of smooth muscle cells. Recent studies have implicated basic fibroblast growth factor (bFGF) as an important mediator of replication in the arterial media, and platelet-derived growth factor as an important mediator of migration. However, the degree of arterial trauma produced during injury has a significant influence on the time of onset of intimal thickening, suggesting that factors released from damaged smooth muscle cells may affect migration. We have investigated the role of one of these factors, bFGF, in smooth muscle cell migration in vivo. We found that 1) deendothelialization of the rat carotid artery results in significantly more migration when it is accompanied by traumatic injury to the underlying smooth muscle; 2) the rate of migration in arteries that have been gently deendothelialized is significantly stimulated by systemic injection of bFGF; and 3) inhibition of bFGF with a blocking antibody significantly reduces the amount of migration after traumatic deendothelializing injury with a balloon catheter. These findings suggest that bFGF plays an important role in the mediation of smooth muscle cell migration after arterial injury. PMID- 8213999 TI - Productive infection of human fetal microglia by HIV-1. AB - Central nervous system disease is a frequent finding in both pediatric and adult AIDS. Microglia have been shown to be the major target of HIV-1 infection in the central nervous system. However, studies in vitro concerning susceptibility of human microglia to HIV-1 infection reported conflicting results; microglia from adult brain showed productive infection by HIV-1, whereas microglia from fetal brain did not. To investigate this further and to define the possible mechanisms responsible for this difference, we prepared highly purified human microglial cell cultures from fetuses of 16 to 24 weeks' gestation and exposed them to monocytotropic (HIV-1 JR-FL and HIV-1 JR-CSF) isolates of HIV-1. Culture supernatants were examined for the presence of p24 antigen for a 4-week period after viral exposure. Concurrently, potential cytopathic effects and cellular viral antigen expression (gp41 and p24) were examined by light microscopy in combination with immunocytochemistry. The results showed that human fetal microglia can be productively infected by HIV-1 as judged by p24 antigen capture assay, syncytia formation, and gp41 and p24 immunoreactivity of infected microglia. In addition, by electron microscopy, numerous viral particles characteristic of HIV-1 were present both in the intracellular and extracellular compartments. Uninfected cultures or astrocytes overgrown in the microglial cultures did not show evidence of infection under identical experimental conditions. These data demonstrate that human fetal microglia, like their adult counterparts, are susceptible to HIV-1 infection in vitro and can support the production of virus. PMID- 8214000 TI - ICAM-3 expression on endothelium in lymphoid malignancy. AB - Intercellular adhesion molecule-3 (ICAM-3), the third receptor for lymphocyte function-associated antigen molecule-1 and a new member of the immunoglobulin superfamily has been recently characterized using specific monoclonal antibodies. In the present study, we show immunocytochemically that ICAM-3 is present on T and B cells in the mantle zones and on a subpopulation of follicular center cells in reactive lymph nodes and only occasionally in endothelium. In 52 cases of Hodgkin's disease, ICAM-3, although present on the majority of the reactive lymphoid cells, was absent from the Reed-Sternberg cells and their variants. However, in 28 cases (54%), there was prominent endothelial staining in small vessels. Similar findings were noted in 16 out of 49 cases (33%) of non-Hodgkin's lymphomas. This finding suggests that analogous to ICAM-1 and ICAM-2, ICAM-3 expression can be induced on endothelial cells in lymphoid neoplasms, probably by an as yet unidentified cytokine-mediated mechanism. PMID- 8214001 TI - Epstein-Barr virus in pyothorax-associated pleural lymphoma. AB - Pleural B-cell lymphoma was found in five patients with a history of pyothorax that was the sequelae of tuberculosis 35 to 47 years previously. Epstein-Barr virus (EBV) DNA was detected in all five pleural tumors by polymerase chain reaction and Southern blot hybridization. The lymphoma cells were shown to express the latent membrane protein-1 and the EBV-encoded nuclear antigen-2 by immunocytochemistry and EBV-encoded small RNA by in situ hybridization. Three cases were shown to be EBV subtype A, whereas the remaining two were subtype B, as determined by differences in the EBV-encoded nuclear antigen-2 nucleotide sequence. The patients also had high titers of antibodies against EBV. These findings suggest that EBV is causally associated with the pleural lymphomas that originate at the site of chronic inflammation and fibrosis with a latent period of more than 40 years. PMID- 8214002 TI - Association of Epstein-Barr virus with gastric carcinoma with lymphoid stroma. AB - Epstein-Barr virus (EBV) has been detected in lymphoepithelioma of nasopharynx and lymphoepitheliomalike carcinomas in various organs. To clarify the association of EBV with gastric carcinoma with lymphoid stroma, which often resembles lymphoepithelioma, the authors examined 22 such cases by polymerase chain reaction and in situ hybridization techniques. In 18 informative cases, EBV DNA was detected by polymerase chain reaction in 14 (77.8%) cases, including lymph node metastases. EBV RNA was detected within the nuclei of carcinoma cells by in situ hybridization in all cases that were positive by polymerase chain reaction. Infiltrating lymphocytes and normal epithelia adjacent to carcinoma were EBV-negative. Southern blot analysis indicated clonal proliferation of tumor cells and episomal form of EBV. These findings suggest that EBV infection occurs before transformation and may be related to oncogenesis of EBV-associated gastric carcinoma. PMID- 8214004 TI - Major histocompatibility complex class I and class II antigen expression in diffuse large cell and large cell immunoblastic lymphomas. Absence of a correlation between antigen expression and clinical outcome. AB - The major histocompatibility complex (MHC) class I (HLA-A, B, C) and class II (HLA-DR) antigens are involved in cell-to-cell recognition and in regulating the immune response. Others have shown previously that MHC class I and class II antigens may be absent in a subset of malignant lymphomas, prompting the hypothesis that the absence of MHC antigen expression may be one of the mechanisms involved in the growth and dissemination of malignant lymphomas (by allowing a neoplasm to escape immune surveillance). To address this hypothesis, we analyzed MHC class I and class II (HLA-DR) antigen expression by diffuse large cell and large cell immunoblastic lymphomas in 88 and 117 patients, respectively, using frozen sections and the monoclonal antibodies W6/32 (HLA-A, B, C), anti beta 2-microglobulin, and L203 (HLA-DR). Although there were no statistically significant clinical differences by MHC class II antigen expression, a small group of patients with MHC class I antigen-negative lymphomas were significantly younger (P = 0.03), less often had small neoplasms (P = 0.03), and were treated with doxorubicin-based chemotherapy more frequently (P = 0.04) than those with antigen-positive lymphomas. However, neither MHC class I nor class II antigen expression by the lymphomas consistently correlated with patient survival or freedom from relapse. This lack of correlation was true for all patients assessed, as well as for the subsets of patients with B-cell lymphomas, T-cell neoplasms, or those treated with doxorubicin-based chemotherapy. In accordance with previously published studies, stage, presence of B symptoms, and treatment with doxorubicin-based chemotherapy were of prognostic importance in univariate or multivariate analyses for survival or freedom from relapse. The findings may be considered evidence against the hypothesis that the absence of MHC class I or II antigen expression by malignant lymphomas plays a role in their tumorigenicity. However, we cannot completely exclude the possibility that the therapies used for this group of patients may have obscured any effect that MHC antigen expression exerts on prognosis. PMID- 8214003 TI - Epstein-Barr virus-latent gene expression and tumor cell phenotype in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. Correlation of lymphoma phenotype with three distinct patterns of viral latency. AB - We investigated 49 acquired immunodeficiency syndrome-related lymphomas (ARLs) for Epstein-Barr virus (EBV) by Southern blotting and in situ hybridization and, in positive cases, used cryostat immunohistology to compare EBV-latent gene expression (EBV encoded small RNA-1 [EBER-1], EBV nuclear antigen-2 [EBNA-2], latent membrane protein-1 [LMP-1] and host cell immunophenotype (CD11a, CD18, CD54, CD58, CD21, CD23, CD30, CD39, CDw70, immunoglobulin) patterns with those reported in other EBV infections. EBV+ immunoblast-rich/large cell ARLs (n = 22) showed three patterns of latency: broad (EBER+EBNA-2+/LMP-1+; n = 9), reminiscent of a lymphoblastoid cell line phenotype; restricted (EBER+/EBNA-2-/LMP-1-; n = 6), similar to endemic Burkitt's lymphoma; and intermediate (EBER+/EBNA-2-/LMP 1+; n = 7), a pattern rarely described in vitro but seen in certain EBV-related malignancies. EBNA-2 expression was associated with extranodal lymphomas. EBV+ Burkitt-type ARLs (n = 11) usually showed the restricted latency pattern (n = 8), but some expressed the intermediate form (n = 3). Adhesion (CD54, CD58) and activation (CD30, CD39, CDw70) molecule expression varied with morphology (immunoblast-rich/large cell versus Burkitt-type), but was not independently correlated with EBV-positivity. CD30 and LMP-1 expression were associated. ARLs show heterogeneity regarding both the presence of EBV and latency pattern. Comparison of these phenotypically distinct lymphoma groups with known forms of EBV infection provides clues to their possible pathogenesis. PMID- 8214005 TI - White pulp reconstitution after human bone marrow transplantation. AB - To reveal the reconstitution process of the white pulp after bone marrow transplantation (BMT), spleens of 24 marrow recipients whose survival times ranged from 34 to 303 days after BMT, were analyzed at the histopathological and immunohistochemical level. Up to 3 months after BMT, the white pulp was atrophic and consisted mainly of T cells forming periarteriolar lymphatic sheaths (PALS). Approximately 100 days after BMT, B cells aggregated in some of the white pulp, forming primary follicles, whereas marginal zones could not be detected. Beyond 4 months after BMT, the PALS, the lymphoid follicle, and the marginal zone of the white pulp could be seen in most of the recipients' spleens. However, the recovery of the marginal zone was poor up to 10 months after BMT. Thus, the white pulp was reconstituted sequentially, beginning in the PALS, followed by reconstitution in lymphoid follicles, and finally in the marginal zone. The development of the PALS corresponded well with the appearance of interdigitating dendritic cell, as did the development of lymphoid follicles with the appearance of follicular dendritic cell. The sequential reconstitution of the white pulp demonstrated in this study provides the morphological basis for the functional immune recovery of marrow recipients. In particular, the delay of the marginal zone reconstitution seems to be responsible for the functional asplenia of long term survivors. PMID- 8214006 TI - Differential expression of tumor necrosis factor and interleukin-6 by peritoneal macrophages in vivo and in culture. AB - To investigate the differences in cytokine regulation in vitro as compared to in vivo, we examined the synthesis of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by peritoneal macrophages in response to lipopolysaccharide (LPS). Mice (CBA/J) were primed with an intraperitoneal injection of complete Freund's adjuvant and after 2 weeks, peritoneal cells were harvested for culture or mice were injected intraperitoneally with LPS for in vivo studies. In ascites fluid, TNF-alpha peaked 1 hour after LPS and returned to baseline levels by 4 hours. In contrast, TNF-alpha in the media reached maximum at 7 hours. Expression of TNF-alpha messenger (m)RNA in vivo was rapid but transient, as levels peaked at 15 minutes and returned to baseline 1 hour after LPS. In contrast, TNF-alpha mRNA in vitro became maximal at 1 hour, but remained elevated to 5 hours after LPS. In vivo, IL-6 in ascites fluid peaked at 2 hours, whereas in vitro, IL-6 continued increasing to 24 hours. In vivo, IL-6 mRNA reached maximum at 30 minutes, but fell below baseline by 1.5 hours after LPS. In contrast, IL-6 mRNA in vitro was sustained at maximal expression between 5 to 9 hours after LPS. These results demonstrate that both TNF-alpha and IL-6 synthesis is more rapid in vivo than in vitro. The rapid kinetics of cytokine expression in vivo must considered when designing strategies to inhibit cytokine action in vivo. PMID- 8214008 TI - Constitutive and cytokine-induced expression of human leukocyte antigens and cell adhesion molecules by human myotubes. AB - Understanding the immunobiology of muscle is relevant to muscular autoimmune diseases and to gene therapies based on myoblast transfer. We have investigated the constitutive and cytokine-induced intra- and extracellular expression of histocompatibility human leukocyte antigens (HLA) and cell adhesion molecules by multinucleated human myotubes using immunofluorescence microscopy. Myotubes constitutively expressed HLA class I but not HLA class II. Exposure to interferon gamma, but not tumor necrosis factor-alpha, induced HLA-DR in the cytoplasm and on the surface membrane of approximately 40 to 95% of cultured myotubes. Surface expression was strongest in perinuclear membrane areas, and cytoplasmic expression was strongest at branching points and at the tips of myotubes. HLA-DP and HLA-DQ were not expressed in detectable amounts. Both interferon-gamma and tumor necrosis factor-alpha induced the intercellular adhesion molecule-1 (CD54) in the cytoplasm and on the surface of nearly all myotubes. The distribution of intercellular adhesion molecule-1 and HLA-DR was similar but not identical in double-positive myotubes. The leukocyte function-associated (LFA) adhesion molecules LFA-1 (CD11a/CD18), LFA-2 (CD2), and LFA-3 (CD58) could not be detected in the cytoplasm or on the surface. Our results indicate that cytokine-induced myotubes can participate in immune interactions with T lymphocytes. PMID- 8214007 TI - Analysis of p60 and p80 tumor necrosis factor-alpha receptor messenger RNA and protein in human placentas. AB - Tumor necrosis factor-alpha (TNF), a pleiotrophic, multifunctional polypeptide factor, has been reported in both normal and infected human placentas. To identify potential targets for this cytokine, the cells in early and late gestation placentas and extraplacental membranes that express the two TNF receptor (TNF-R) genes, p60 and p80, were identified by using in situ hybridization and immunocytochemistry. Gestation-related, cell lineage-specific differences in steady-state levels of p60 and p80 TNF-R messenger RNA were observed. p60 TNF-R messenger RNA predominated at both early and late stages of gestation, being high in both mesenchymal and trophoblastic cell lineages. By contrast, p80 TNF-R messenger RNA was abundant only in intermittent stretches of first trimester syncytiotrophoblast and term placental mesenchymal cells. Overall, intensities of the TNF-R hybridization signals were stronger in term than in first trimester tissues. Transcription of the two TNF-R genes was confirmed by Northern blot hybridization. Translation was verified in all samples by immunohistology using polyclonal antibodies specific for the receptor proteins. p60 and p80 TNF-R proteins were identified both intracellularly and in maternal and fetal blood. Because TNF-Rs exist in both membrane-bound and soluble forms, the results of this study are consistent with the postulate that placental TNF-R have two critical functions: 1) modulation of TNF utilization by specific placental cell lineages during the course of pregnancy; and 2) protection against excessive TNF produced during infections. PMID- 8214009 TI - A tumorigenic murine Sertoli cell line that is temperature-sensitive for differentiation. AB - The Sertoli cell is the epithelial cell within the seminiferous tubule responsible for supporting germ cells. Most current in vitro studies of Sertoli cell function use primary cultures because of the limited number of available Sertoli cell lines. In addition, few in vivo models of Sertoli cell malignancy have been described. In this study, a tumorigenic Sertoli cell line was developed by infection of isolated murine Sertoli cells by simian virus 40 tsA255; the ts mutation causes the inactivation of the large T antigen at elevated temperatures. A cloned Sertoli cell line, called S14-1, demonstrated temperature-dependent growth in soft agar and formed tumors in nude mice. Electron microscopy of the S14-1-derived tumor revealed extensive basal intercellular junctions and tubulobulbarlike processes supporting its Sertoli cell origin. Cytogenetic analysis showed that S14-1 cells were aneuploid with an average of 70 chromosomes per cell. At the nonpermissive (40 C) temperature, S14-1 cells in vitro demonstrated a reduced growth rate, enhanced secretion of transferrin, and increased expression of sulfated glycoprotein-2 messenger RNA, indicating the cells manifested increased differentiation following large T antigen inactivation. The murine S14-1 Sertoli cell line should be useful for both in vitro studies of Sertoli cell function and in vivo studies of Sertoli cell malignancy. PMID- 8214010 TI - Expression of parathyroidlike protein in normal, proliferative, and neoplastic human breast tissues. AB - Parathyroidlike peptide (PLP), or parathyroid hormone-related protein, is a protein of uncertain biological function that is structurally homologous to parathyroid hormone. Immunohistochemical studies have identified aminoterminal epitopes of PLP in breast carcinomas, but not in normal breast. In the present studies, immunohistochemistry and in situ hybridization were performed to evaluate further expression of PLP in normal, proliferative, and neoplastic breast tissues. Using a polyclonal antibody that recognizes epitopes within the middle and carboxyl-terminal domains of PLP, immunoreactive protein was detected within the cytoplasm of lobular and ductal epithelial cells in all normal and fibrocystic breast tissues from 74 patients. The intensity of cytoplasmic staining was increased in association with lactation, adenosis, and simple or atypical ductal hyperplasia and decreased in atrophic lobules. Cytoplasmic reactivity was also observed in 69% (56 of 81) of breast adenocarcinomas. Expression of immunoreactive PLP was inversely correlated with tumor stage and extent of nodal involvement at the time of diagnosis. However, there was no significant correlation with tumor grade, patient age, or hormone receptor status. In situ hybridization studies confirmed the epithelial expression of PLP messenger RNA in PLP-positive normal and neoplastic breast tissue. Interestingly, tumor-associated calcifications were identified in 43% of PLP-positive carcinomas, but in only 12% of PLP-negative carcinomas (P < 0.007). Our results suggest that PLP plays some role in the normal differentiated function of mammary epithelial cells and are consistent with the hypothesis that expression of this protein influences local calcium metabolism. PMID- 8214011 TI - Localization of dystrophin and beta-spectrin in vacuolar myopathies. AB - We examined the expression of the cytoskeletal proteins dystrophin and beta spectrin on vacuolar boundaries in vacuolar myopathies. We also localized utrophin, a dystrophin homologue, and laminin, which served as a marker for the basal lamina. Four types of vacuoles were identified. Type 1 vacuoles, found in all diseases, were lined by laminin, dystrophin, and beta-spectrin and arose from infoldings of the basal lamina and sarcolemma into splitting or branching fibers. Type 2 vacuoles were lined by dystrophin and beta-spectrin and were most common in adult acid maltase deficiency, chloroquine myopathy, and periodic paralysis. Traces of utrophin were also noted on the boundaries of some type 2 vacuoles, but only in those fibers that also expressed utrophin on their surface membrane. Type 3 vacuoles were lined by small patches of dystrophin and beta-spectrin and occurred in any vacuolar myopathy. Type 4 vacuoles were unlined by any of the above antigens and were most common in infantile acid maltase deficiency and in the nonlysosomal glycogenoses. Immunoelectron microscopy confirmed the dystrophin label on vacuolar boundaries but revealed no reaction product on any other membranous component within the muscle fiber. We conclude that dystrophin and beta-spectrin provide cytoskeletal support for a species of membrane-bound vacuoles in diverse myopathies. PMID- 8214012 TI - Cell density modulates growth, extracellular matrix, and protein synthesis of cultured rat mesangial cells. AB - Mesangial cell (MC) hyperplasia and accumulation of extracellular matrix are hallmarks of chronic glomerular disease. The present in vitro study examined the effects of cell density on growth, extracellular matrix formation, and protein synthesis of cultured rat MCs. A negative linear relationship was found between initial plating density and DNA synthesis per cell after 24 hours incubation in medium with 10% fetal calf serum (range: 1 x 10(3) to 7 x 10(5) MCs/2cm2, r = 0.996, P < 0.001). Enzyme-linked immunosorbent assay of the amount of fibronectin in the conditioned medium after 72 hours showed a negative relationship with increasing cell density. In contrast, the amount of cell-associated fibronectin increased to maximal values in confluent cultures, and no further increase was seen at supraconfluency. The relative collagen synthesis in the conditioned medium and cell layer--assessed by collagenase digestion after 5 hours [3H]proline pulse labeling--showed a similar pattern. Secreted collagen decreased with increasing cell density from 3.4% to 0.2% of total protein synthesis. In contrast, cell-associated collagen increased from 1.1% to 11.8% of newly synthesized protein until confluency followed by a decrease to 4.2% at supraconfluency. Specific immunoprecipitation of collagen types I, III, and IV revealed a significant (twofold) increase in collagen I synthesis per cell at confluency. Collagen III and IV synthesis was not affected by cell density. Specific protein expression in both the medium and cell layer were analyzed by two-dimensional polyacrylamide gel electrophoresis (150 to 20 kd, pI 5.0 to 7.0) after 20 hours steady-state metabolic labeling with [35S]methionine. Supraconfluent MCs displayed overexpression of 10, underexpression of four, new expression of five, and changed mobility of three different intracellular proteins. Of interest was the overexpression of two proteins (89 kd, pI 5.31 and 72 kd, pI 5.32) that were identified by immunoblotting as the stress proteins heat-shock protein 90 and glucose-related protein 78, respectively. The progressive increase of cell-associated fibronectin and collagens, particularly collagen type I, in confluent MCs resembles extracellular matrix accumulation in glomerular disease. The increased expression of stress proteins in supraconfluent MCs is of interest in view of the analogy between glomerulosclerosis and atherosclerosis in which stress proteins are expressed in high concentrations. PMID- 8214013 TI - In vivo role of phagocytic synovial lining cells in onset of experimental arthritis. AB - The in vivo role of phagocytic synovial lining cells (SLC) was studied in acute experimental arthritis in the mouse. SLCs were selectively depleted by injecting liposomes encapsulating the drug dichloromethylene diphosphonate (CL2MDP, Clodronate). Optimal depletion of phagocytic lining cells occurred 7 days after CL2MDP liposome injection. Eliciting an immune complex-mediated arthritis in SLC depleted knee joints largely prevented inflammation if compared to control arthritic knee joints. Joint swelling and influx of inflammatory cells into the joint cavity was markedly diminished. Cartilage damage, in this model related to influx of inflammatory cells, was significantly decreased. Reduced influx of inflammatory cells (mainly polymorphonuclear neutrophils) was correlated to a decreased production of chemotactic factors as measured in washouts of arthritic joints in a two-compartment Transwell system. Interleukin-1-driven chemotactic factors seem to be involved. Interleukin-1 levels were significantly lowered in SLC-depleted arthritic knee joints as compared to controls. Injection of recombinant murine interleukin-1 in SLC-depleted knee joints caused less influx of inflammatory cells as compared to injection into control knee joints. A specific damage of CL2MDP liposome treatment to synovial blood vessels was excluded as intraarticular injection of human recombinant C5a in lining-depleted knee joints showed similar influx of inflammatory cells if compared to human recombinant C5a injection in control knee joints. This study indicates that in immune complex-mediated arthritis, phagocytic lining cells regulate the onset of the inflammatory response. PMID- 8214015 TI - Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides. AB - Extracellular ATP, at micromolar concentrations, induces significant functional changes in a wide variety of cells and tissues. ATP can be released from the cytosol of damaged cells or from exocytotic vesicles and/or granules contained in many types of secretory cells. There are also efficient extracellular mechanisms for the rapid metabolism of released nucleotides by ecto-ATPases and 5' nucleotidases. The diverse biological responses to ATP are mediated by a variety of cell surface receptors that are activated when ATP or other nucleotides are bound. The functionally identified nucleotide or P2-purinergic receptors include 1) ATP receptors that stimulate G protein-coupled effector enzymes and signaling cascades, including inositol phospholipid hydrolysis and the mobilization of intracellular Ca2+ stores; 2) ATP receptors that directly activate ligand-gated cation channels in the plasma membranes of many excitable cell types; 3) ATP receptors that, via the rapid induction of surface membrane channels and/or pores permeable to ions and endogenous metabolites, produce cytotoxic or activation responses in macrophages and other immune effector cells; and 4) ADP receptors that trigger rapid ion fluxes and aggregation responses in platelets. Current research in this area is directed toward the identification and structural characterization of these receptors by biochemical and molecular biological approaches. PMID- 8214016 TI - Angiotensin II type 2 receptor-modulated changes in potassium currents in cultured neurons. AB - We have previously shown that angiotensin II (ANG II) stimulates an increase in net outward ionic current (Ino) in neurons cocultured from neonate rat hypothalamus and brain stem, an effect mediated by ANG II type 2 (AT2) receptors. Ino consists mainly of K+ and Ca2+ currents, and in the present study we used whole cell voltage clamp procedures to define which of these currents are modulated by AT2 receptors. We determined that ANG II (50-100 nM) stimulated both transient K+ current (IA) and delayed-rectifier K+ current (IK) in cultured neurons. The effects were mediated by AT2 receptors (blocked by 1 microM PD 123177 but not by 1 microM losartan). For both IA and IK, ANG II elicited an increase in maximal conductance. By contrast, ANG II altered neither Ca(2+) activated K+ current nor Ca2+ current. Our data demonstrate discrete AT2 receptor mediated effects of ANG II on IA and IK in cultured neonate neurons. Importantly, these data provide an electrophysiological basis for behavioral or physiological effects (as yet undefined) mediated by this ANG II receptor subtype in the brain. PMID- 8214014 TI - Rous-Whipple Award Lecture. Atherosclerosis: a defense mechanism gone awry. PMID- 8214017 TI - Changes in calcium channel current densities in rat colonic smooth muscle cells during development and aging. AB - The age-related changes of Ca2+ channel currents were investigated in freshly isolated single smooth muscle cells from the circular layer of the distal colon from the rat using the whole cell voltage clamp technique. Under physiological conditions (Ca2+ concentration of 2.0 mM), the averaged total Ca2+ current density increased markedly from 1.25 pA/pF in the newborn rat to 6.46 pA/pF in the 60-day-old rat; it then gradually declined with aging. Two types of Ca2+ channel currents seemed to be present; one type possessed more negative threshold potentials (-70 to -60 mV) when the cells were held at -80 or -100 mV and inactivated quickly. The voltage for peak current was -20 to -10 mV, and the reversal potential was +60 to +70 mV. This current was highly sensitive to low concentrations of Ni2+ (30 microM) but was resistant to nifedipine, diltiazem, cadmium, and tetrodotoxin. In contrast, the other type of Ca2+ channel current possessed more positive threshold potential (-40 mV) and inactivated more slowly. The voltage for peak current was 0 mV, and the reversal potential was +60 to +70 mV. This current was insensitive to low concentrations of Ni2+ but highly sensitive to nifedipine, diltiazem, and cadmium. These results suggest that the fast inactivating (transient) current might be T-type Ca2+ current [ICa(T)], and such cells were ICa(T) positive cells; whereas the sustained Ca2+ current was L type Ca2+ current [ICa(L)], and such cells were ICa(L) positive cells. Our results showed that the fraction of ICa(T) positive cells increased with development; the current densities of both ICa(L) and ICa(T) also increased with development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214018 TI - Physiological programmed cell death in thymocytes is induced by physical stress (exercise). AB - Thymic involution occurs in young adult male Wistar rats that have performed two runs to exhaustion (RTE) on a treadmill, separated by a 24-h rest period, but not after a single RTE. We were interested in determining whether programmed cell death (or apoptosis) is responsible for the corresponding decrease in T-cell numbers in the thymus. DNA fragmentation, which is an early feature of apoptosis and easily detected by agarose gel electrophoresis, was found in rat thymocytes after the second RTE (the duration of 1 RTE was approximately 5 h). It was also detected after a single RTE or after 2.5 h of running only, and the levels of DNA fragmentation were always roughly similar. In addition, DNA fragmentation was decreased in RU-486 vs. vehicle-treated rats that had run for 2.5 h. These results indicate that physical stress induces glucocorticoid receptor-mediated apoptosis of rat thymocytes. Because apoptosis is induced to similar levels during mild and severe physical stresses, some additional events must be associated to provoke thymic involution. PMID- 8214019 TI - Culture-induced alterations in alveolar type II cell Na+ conductance. AB - Changes in Na+ transport in rat alveolar type II (ATII) cells during culture were quantified and related to alterations in spatial distribution of proteins antigenically related to amiloride-sensitive Na+ channels. Adult rat ATII cells were cultured for periods ranging from 24 to 96 h. When patch clamped in the whole cell mode, both freshly isolated and cultured ATII cells exhibited outwardly rectified Na+ currents. At 0 and 24 h in culture, these currents were equally inhibited by amiloride, benzamil, and 5-(N-ethyl-N-isopropyl)-2',4' amiloride (inhibitory constant approximately 1 microM). These conductive pathways were equally permeable to Na+ and K+. Immunocytochemical localization at 0 or 24 h in culture revealed the presence of plasma membrane antigenic sites; after 48 h, the appearance of intracellular antigenic sites increased significantly. A single band of molecular mass 135 kDa in membrane proteins of freshly isolated ATII cells was recognized in Western blots; at 48 h in culture, two lower bands with molecular masses of 75 and 65 kDa were detected in either membrane or cytoplasmic proteins. Photolabeling with 2'-methoxy-5'-nitrobenzamil showed that the 135-, 75-, and 65-kDa bands contained amiloride-binding sites. These results suggest the presence of low amiloride affinity conductive pathways in freshly isolated and cultured ATII cells. Culturing ATII cells resulted in internalization and possible breakdown of these pathways and decreased Na+ transport. PMID- 8214020 TI - Cl- secretion by cultured shark rectal gland cells. III. Ca2+ regulation of apical membrane Cl- conductance. AB - Calcium ionophores (ionomycin and A-23187) were employed to assess the effects of increased intracellular Ca2+ concentration ([Ca2+]i) on apical membrane Cl- conductance (GaCl) and rate of transepithelial Cl- secretion in cultured shark rectal gland (SRG) cells. Apical 2 microM ionomycin induced dramatic changes in cellular electrophysiological properties: the apical membrane electrical potential difference (V(a)) depolarized from -66 mV to -46 mV, the fractional resistance of the apical membrane (fRa) decreased from 0.88 to 0.23, and the transepithelial electrical potential difference (Vab) increased slightly from +1.2 mV to +1.4 mV. These effects result from increased GaCl because apical low Cl- shark Ringer (SR) depolarized V(a) by 32 mV and increased fRa from 0.23 to 0.36. Ionomycin-stimulated Vab or short-circuit current (Isc) results largely from increased Cl- secretion because approximately 80% of the increase in Isc is Cl- dependent. Establishing the Ca2+ dependence of ionophore activation of GaCl was confounded because apical low-Ca2+ SR [Ca2+ concentration ([Ca2+]) 1 mM to 0.1 microM] alone activated this conductive pathway. To establish the Ca2+ dependence of ionophore action, we assessed the effect of ionomycin on Isc in low Ca2+ SR ([Ca2+] = 0.1 microM) and in SR. In low-Ca2+ SR, apical ionomycin stimulated Isc by 14.0 microA/cm2. In SR (normal [Ca2+]), ionomycin increased Isc further by 27.0 microA/cm2. Superfusing the basolateral surface with 2 microM ionomycin for 8-16 min failed to activate GaCl. In every case, subsequent superfusion of the apical surface with ionophore for 1.5-2 min activated GaCl. Bilateral 4 microM indomethacin (45-min superfusion) failed to block the ionomycin-induced GaCl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214021 TI - Uptake and caffeine-induced release of calcium in fast muscle fibers of Xenopus laevis: effects of MgATP and P(i). AB - To elucidate the origin of the reduction in force during prolonged muscle fatigue, the dependency of Ca2+ uptake and release on MgATP and P(i) concentration was studied in saponin-skinned fast skeletal muscle fibers of the iliofibularis muscle of Xenopus laevis at 3 degrees C. The sarcoplasmic reticulum was loaded with Ca2+ for 5 min at pCa 7.0. The amount of Ca2+ released was derived from the area of the caffeine-induced force response. Ca2+ uptake increased with the MgATP concentration present during loading. It was half maximal at 20 microM and saturated at higher concentrations. The kinetics of Ca2+ release were affected for MgATP concentrations between 0.1 and 0.5 mM or less, but the amount of Ca2+ released by caffeine in ATP-free solutions was substantial. Phosphate (15 mM) only slightly reduced Ca2+ uptake when the loading period was short (1 min). It is unlikely, therefore, that the reduction in MgATP concentration contributes to the depression of Ca2+ released from the sarcoplasmic reticulum during fatigue. The increase in P(i) concentration could play a small role by reducing Ca2+ uptake. PMID- 8214022 TI - Muscarinic stimulation of tracheal smooth muscle cells activates large conductance Ca(2+)-dependent K+ channel. AB - We investigated the regulation of the large-conductance Ca(2+)-dependent K+ (KCa) channel by acetylcholine (ACh) in freshly dissociated tracheal smooth muscle cells. Channels were recorded in the cell-attached patch configuration, and cells were stimulated with ACh, muscarine, or caffeine. We identified KCa channel activity based on 1) the voltage dependence of channel opening; 2) the large unitary conductance (242 +/- 5 pS with symmetrical 135 mM K+); 3) dependence of the reversal potential on the [K+] gradient, shifting 56 +/- 3 mV/10-fold change in extracellular [K+]; and 4) opening of channels after elevation of cytosolic free Ca2+ concentration ([Ca2+]i) using the Ca2+ ionophore A23187. When cells were bathed either in a physiological saline solution or a solution containing 135 mM K+ (to clamp cell membrane potential near 0 mV), ACh caused contraction of cells and activation of voltage-dependent channels. With 135 mM extracellular K+, the channels activated by ACh had a unitary conductance of 247 +/- 10 pS, and currents reversed near the K+ equilibrium potential (-1 +/- 1 mV). The effects of ACh were reversible, blocked by atropine, and mimicked by muscarine. From these characteristics we conclude that muscarinic stimulation of canine tracheal smooth muscle cells leads to activation of the large-conductance KCa channel. Because the KCa channels were isolated from ACh by the patch pipette, the increased channel activity was probably mediated by a cytosolic second messenger. ACh shifted the threshold for KCa channel opening to less positive membrane potentials, similar to that seen with elevation of [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214023 TI - Pharmacological characterization of muscarinic receptors in neonatal rat cardiomyocytes. AB - [N-methyl-3H]scopolamine methylchloride ([3H]NMS) was used to characterize the muscarinic receptors (mAChRs) in the intact cardiomyocytes. The specific binding of [3H]NMS was proportional to cell concentration, saturable with respect to [3H]NMS concentration, and time dependent. Scatchard analysis of binding isotherms showed that [3H]NMS bound to the freshly isolated and cultured cardiomyocytes with dissociation constants of 275 +/- 64 and 207 +/- 20 pM as well as maximum receptor densities of 0.13 +/- 0.09 and 5.36 +/- 0.20 fmol/10(5) cells, respectively. Heterogeneity of mAChRs was demonstrated by competitive binding experiments against [3H]NMS with M2 and M3 antagonists. These receptors (80%) exhibited high affinities for 11-([2-[(diethylamino)methyl]-1-piperidinyl] acetyl)-5,11-dihydro- 6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX-116) and methoctramine similar to those of M2 subtype. The low-affinity M2 antagonist binding constants were close to those reported for M3 receptors and possessed high affinity for 4-diphenylacetoxyl-N-methylpiperidine (4-DAMP) and hexahydrosiladifenidol. On the basis of biochemical studies, AF-DX-116 blocked adenosine 3',5'-cyclic monophosphate (cAMP) inhibition with high affinity (pKB 7.4), while it antagonized inositol phosphate formation with low affinity (pKB 6.5). 4-DAMP possessed high affinity in blocking inositol phosphate formation (pKB 9.0) and low affinity for antagonism of cAMP inhibition (pKB 7.7). Although no other muscarinic receptor mRNA has been detected in these cells, these data suggest the presence of a second population of mAChRs, which may not be identical to the classical cardiac "M2" receptors. PMID- 8214024 TI - Ca-dependent action of cocaine on K current in freshly dissociated dorsal root ganglia from rats. AB - The actions of cocaine on K currents were analyzed in enzymatically dissociated neurons from adult rat dorsal root ganglia. The whole cell voltage clamp configuration was used to determine that in the presence of Ca cocaine inhibited a K conductance that was activated from a holding potential of -55 mV. The cocaine concentration that decreased K currents half-maximally was 18 microM. At a concentration of 40 microM, cocaine had no significant effect on K current remaining in the absence of external Ca, whereas at 80 microM a significant 17% depression of this current was observed. Large transient K currents occurring with depolarizations from -90 mV were also resistant to 40 microM cocaine, suggesting that cocaine specifically inhibits a Ca-dependent K current. Ca currents elicited from a holding potential of -55 mV were largely unaltered by 40 microM cocaine. The data suggest that cocaine may be a useful tool for experimental blockage of Ca-dependent K currents and also provide additional insight into the overall actions and toxicity of the drug. PMID- 8214025 TI - Thyroid hormone specifically regulates skeletal muscle Na(+)-K(+)-ATPase alpha 2- and beta 2-isoforms. AB - The purpose of this study was to determine the pattern of thyroid hormone (triiodothyronine, T3) regulation of the Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) alpha- and beta-subunit expression in skeletal muscle, which expresses alpha 1-, alpha 2-, beta 1-, and beta 2-subunits, and compare it with that seen in kidney, which expresses only alpha 1 and beta 1. Three steady states were studied: hypothyroid, euthyroid, and hyperthyroid (hypothyroids injected daily with 1 microgram T3/g body wt for 2-16 days). Protein and mRNA abundance, determined by Western and Northern analysis, were normalized to a constant amount of homogenate protein and total RNA, respectively. In skeletal muscle, there was no change in alpha 1- or beta 1-mRNA or protein levels in the transition from hypothyroid to hyperthyroid. However, alpha 2 was highly regulated; mRNA reached a new steady-state level of fivefold over hypothyroid by 8 days of T3 treatment and protein abundance increased threefold. In addition, beta 2-mRNA and protein were detected in skeletal muscle and were also highly regulated by T3; beta 2 mRNA increased nearly fourfold over hypothyroid level, and beta 2-protein abundance increased over twofold. In kidney in the transition from hypothyroid to hyperthyroid, there were coordinate 1.6-fold increases in both alpha 1- and beta 1-mRNA abundance that predicted the observed changes in alpha 1- and beta 1 protein levels and Na(+)-K(+)-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214026 TI - Cross-bridge kinetics during shortening in early and sustained contraction of intestinal smooth muscle. AB - Mechanisms responsible for the decrease in shortening velocity after prolonged contraction ("latch" state) were investigated at identical force during early (20 s, "phasic") and sustained (5 min, "tonic") phases of high-K+ (25-30 mM) contractions in smooth muscle of guinea pig taenia coli. Cytoplasmic Ca2+ concentration, myosin light-chain phosphorylation, and maximum shortening velocity all declined from 20 s to 5 min of contraction. The time course of shortening following isotonic quick release was biexponential, with a fastest rate constant of approximately 80 s-1 in both phasic and tonic contractions. Stiffness was identical in phasic and tonic contraction; however, after a release to slack length and unloaded shortening, stiffness during restretch was greater in tonic contraction (51 vs. 43% of isometric stiffness after 16 ms of unloaded shortening). Stiffness decreased after release with a rate constant of approximately 200 s-1, slightly greater in phasic than in tonic contraction. The results indicate that the number of attached cross bridges during unloaded shortening, while substantially reduced relative to the isometric value, is higher in latch than in nonlatch, consistent with a lower detachment relative to attachment rate. PMID- 8214027 TI - Disulfide-linked aggregation of thyroglobulin normally occurs during nascent protein folding. AB - In the endoplasmic reticulum (ER) of cultured porcine thyrocytes, newly synthesized thyroglobulin (Tg, the precursor in thyroid hormone synthesis) initially forms protein aggregates, which are dissolved into monomers and then assembled to dimers, before intracellular transport and secretion. However, studies suggest that in different physiological states and in different cells, folding efficiency in the ER may vary; with this in mind we have set out to further characterize the phenomenon of nascent Tg aggregation. In primary cultured thyrocytes, fresh thyroid follicular tissue (of porcine and rat origin), and the FRTL-5 cell line, nascent Tg appears transiently aggregated with mispaired, interchain disulfide linkages. Using a cell lysis procedure that maximally inhibits proteolysis as well as artifactual disulfide formation, Tg aggregates of M(r) > or = 2,000,000 can be stably isolated by gel filtration. Furthermore, stimulation with thyrotropin and other hormones that enhance Tg production may alter but does not eliminate formation of these aggregates. We conclude that transient disulfide-linked aggregation occurs normally during Tg folding in the ER of thyroid epithelial cells. PMID- 8214028 TI - Nitric oxide synthesis is impaired in glutathione-depleted human umbilical vein endothelial cells. AB - Human endothelial cells cultured from umbilical vein (HUVEC) were tested for their ability to synthesize nitric oxide (NO), which has been identified as an endothelium-derived relaxing factor. The synthesis of this free radical (detected as citrulline, which is produced stoichiometrically with NO from arginine) in HUVEC is Ca2+ dependent, is increased sevenfold by the calcium ionophore ionomycin, and accounts for most basal and ionomycin-induced guanosine 3',5' cyclic monophosphate (cGMP) production. Loading of cells with reduced glutathione (GSH), but not with N-(2-mercaptopropionyl)- glycine (MPG), led to increased citrulline production, both basally and after ionomycin stimulation. When the cells were depleted of GSH by incubation with 1-chloro-2,4-dinitrobenzene (CDNB), citrulline synthesis and cGMP production were inhibited in a concentration dependent way. CDNB was not cytotoxic and did not inhibit cGMP increase elicited by sodium nitroprusside; cell loading with GSH (but not with MPG) relieved the block of citrulline synthesis. These results suggest that GSH is necessary in HUVEC for NO synthesis rather than for the NO effect on guanylate cyclase. PMID- 8214029 TI - Structural changes in the apical membrane of lamprey chloride cells after acclimation to seawater. AB - Freeze-fracture replicas demonstrate that the apical membrane of the chloride cells of young adult lampreys (Geotria australis) undergoes a structural change when the animal is acclimated from freshwater to seawater. Although the particles on both the P face and the E face of this membrane are randomly distributed in freshwater animals, they are usually arranged in clusters on both fracture faces in seawater-acclimated animals. Light optical diffraction analysis demonstrates that the particles forming the clusters are periodically arranged. Although comparable clusters of particles have not been recorded in other epithelial membranes that are engaged in transporting ions into a hypertonic environment, they may be involved in the final step of Cl- secretion by the chloride cells of lampreys in seawater. PMID- 8214030 TI - Sphingolipids as mediators of effects of platelet-derived growth factor in vascular smooth muscle cells. AB - The role of sphingolipids in mediating the action of platelet-derived growth factor (PDGF) has been investigated in the vascular smooth muscle-derived A7r5 cell line. L-Cycloserine (2 mM), an inhibitor of sphingolipid synthesis, caused time-dependent inhibition of [3H]serine incorporation into [3H]sphingomyelin in A7r5 cells. PDGF-AB (10 ng/ml), PDGF-BB (10 ng/ml), or sphingosine (10 microM) independently stimulated [3H]thymidine incorporation into DNA in A7r5 cells. L Cycloserine (2 mM) inhibited stimulation of DNA synthesis by both PDGF-AB and PDGF-BB. L-Cycloserine (2 mM, 16 h) did not affect the ability of PDGF or sphingosine to increase intracellular free calcium ([Ca2+]i) in A7r5 cells loaded with the fluorescent indicator fura 2. Measurement of adenine nucleotide levels in A7r5 cell extracts by reverse-phase high-performance liquid chromatography indicated that treatment with L-cycloserine did not adversely affect cellular metabolism. To determine directly whether PDGF activates sphingolipid metabolism, A7r5 cells were labeled with [3H]serine for 48 h and then treated with PDGF-AB (10 ng/ml) for 1 h. Sphingolipids were separated by thin-layer chromatography and quantified by liquid scintillation counting. PDGF-AB stimulated an increase in [3H]sphingosine from 25.5 +/- 3.0 to 37.5 +/- 4.1 counts.min-1 (cpm).micrograms protein-1 and a concomitant decrease in [3H]ceramide from 24.3 +/- 3.2 to 18.5 +/ 2.9 cpm/micrograms protein. These data suggest that the PDGF-stimulated increase in [Ca2+]i is not sufficient for induction of DNA synthesis and that mitogenic effects of PDGF in vascular smooth muscle cells are mediated by sphingolipid metabolism. PMID- 8214031 TI - Vasopressin depolymerizes apical F-actin in rat inner medullary collecting duct. AB - In amphibian bladder, arginine vasopressin (AVP) depolymerizes F-actin in the apical region of the granular cell, promoting fusion of water channel-carrying vesicles with the apical membrane. We now report the effect of AVP on F-actin in the mid- and terminal segments of rat inner medullary collecting duct (IMCD2 and IMCD3). In IMCD3, 5 min of stimulation by 2.5-250 nM AVP significantly depolymerized F-actin by 13-24% in whole cell assays employing the rhodamine phalloidin binding technique. The IMCD2 was more sensitive, responding to subnanomolar (0.25 nM) AVP with 6 +/- 2% depolymerization. Depolymerization occurred as early as 2 min after 2.5 and 25 nM but not 250 nM AVP. 8 Bromoadenosine 3',5'-cyclic monophosphate depolymerized F-actin in IMCD3 at both 2 and 5 min. Immunogold labeling of the apical actin pool in IMCD3 principal cells was reduced by 26 +/- 5% (P < 0.05) by 2.5 nM AVP; the lateral and basal pools showed no significant changes. Capillary endothelial, thin limb of Henle, and intercalated cells showed no changes in immunogold labeling after AVP. Thus reorganization of the apical actin network by AVP is a consistent finding in both mammalian and amphibian target cells. PMID- 8214032 TI - Swelling-activated K fluxes in vascular endothelial cells: volume regulation via K-Cl cotransport and K channels. AB - K efflux pathways responsible for regulatory volume decrease (RVD) were examined in bovine aortic endothelial cells. Hypotonic swelling produced a rapid and reversible threefold increase in bumetanide-insensitive 86Rb efflux. Swelling activated 86Rb efflux was inhibited 43% when Cl was replaced with NO3, and this Cl-dependent efflux was inhibited by 1 mM furosemide. Neither Cl replacement nor furosemide inhibited the efflux stimulated by a Ca ionophore (A23187) in isotonic medium. Swelling-activated 86Rb efflux was also inhibited by 4,4' diisothiocyanostilbene-2,2'-disulfonate but not by dinitrostilbenedisulfonate. Cell swelling induced a volume-regulatory K loss that was incomplete in hypotonic medium but complete and more rapid when bumetanide was added or when cells were swollen isosmotically. K loss in the presence of bumetanide was partially blocked by furosemide. We conclude that two separate swelling-activated K fluxes mediate RVD in aortic endothelial cells: a Cl-dependent, furosemide-sensitive, but bumetanide-insensitive flux that is consistent with K-Cl cotransport, and a Cl independent efflux that presumably is mediated by K channels. PMID- 8214033 TI - Endothelial cell phospholipid distribution and phospholipase activity during acute and chronic hypoxia. AB - We have previously reported alterations in cyclooxygenase metabolism in cultured aortic and pulmonary arterial endothelial cells exposed to acute and chronic hypoxia. These alterations depended on the duration and degree of the hypoxic exposure, on the vascular bed from which the endothelial cells were derived, and possibly on the availability of arachidonic acid secondary to modifications in metabolic substrate, membrane phospholipids, and/or membrane phospholipase activity. To investigate this last point further, we have compared plasma membrane phospholipid distribution and phospholipase activity in cultured aortic and pulmonary arterial endothelial cells exposed to both acute and chronic hypoxia, using two different precursors (acetic acid and arachidonic acid) and three different membrane preparations (cell homogenates, partially purified plasma membranes, and highly purified plasma membranes). We found that exposure to acute and chronic hypoxia has profound and complicated effects on endothelial cell phospholipid composition and phospholipase activity and that these effects depend on the origin of the endothelial cells and the duration of hypoxia. Furthermore, we found that the alterations in endothelial cell phospholipid distribution in response to hypoxia depend on the purity of the plasma membrane preparation and the metabolic precursor used to study phospholipid metabolism. Finally, these studies suggested that alterations in phospholipids during hypoxia occurred to a greater extent in compartments of endothelial cells other than the plasma membranes and that the well-recognized tolerance of endothelial cells to hypoxia may be due, in part, to preservation of the integrity of their plasma membranes during exposure to acute and chronic hypoxia. PMID- 8214034 TI - Histamine stimulates a biphasic calcium response in the human tracheal epithelial cell line CF/T43. AB - We have studied the cytosolic free Ca2+ concentration ([Ca2+]i) response to histamine and other inflammatory mediators in a cystic fibrosis tracheal epithelial cell line (CF/T43) using digital fluorescence imaging. Brief pulses of histamine increased [Ca2+]i in a concentration-dependent manner with threshold, half-maximal, and maximal responses at approximately 5 microM, 120 microM, and 10 mM, respectively. The calcium response to sustained histamine exposure was markedly biphasic, consisting of an early peak (to approximately 2.4 microM [Ca2+]i) followed by a smaller second peak that lasted 45-60 s. Neither peak was directly dependent on Ca2+ influx. In contrast, stimulation with bradykinin gave a single peak followed by a smooth decay back to baseline levels. Sustained perfusion with histamine did not affect the bradykinin response, which is known to be mediated by inositol 1,4,5-trisphosphate (IP3). The H1-type histamine receptor blockers mepyramine, diphenhydramine, and (+)-chlorpheniramine were potent antagonists of the histamine response. Diphenhydramine was also a weak agonist at high concentrations (> or = 1 mM) and gave a biphasic response similar to that with histamine. The H2-type receptor blocker cimetidine and the H3-type receptor blocker thioperamide had no effect. Indomethacin failed to inhibit the second phase of the histamine-stimulated [Ca2+]i response, suggesting that the second [Ca2+]i peak is not due to secondary production of prostaglandins. Neomycin, which inhibits IP3 production, completely abolished the [Ca2+]i response to bradykinin stimulation but did not affect the second phase of the histamine response. The biphasic nature of the histamine response, the insensitivity of the second [Ca2+]i peak to neomycin, and the independence of bradykinin and histamine responses suggest that histamine may modulate [Ca2+]i through multiple IP3 and non-IP3 pathways. PMID- 8214035 TI - Effects of repeated eccentric contractions on structure and mechanical properties of toad sartorius muscle. AB - It has been proposed that lengthening of active muscle at long lengths is nonuniformly distributed between sarcomeres, with a few being stretched beyond overlap and most hardly being stretched at all. A small fraction of the overstretched sarcomeres may fail to reinterdigitate on subsequent relaxation, leading to progressive changes in the muscle's mechanical properties. Sartorius muscles of the toad Bufo marinus were subjected to repeated lengthening (eccentric) contractions at long lengths, while controls were passively stretched and then contracted isometrically or stretched at short lengths. The muscles undergoing eccentric contractions showed a progressive shift to the right of the length-tension curve, a fall in the yield point during stretch, an increase in slope of the tension response during stretch, and a fall in isometric tension. In control muscles, changes, if any, were significantly less. In electron micrographs, muscle fibers that had been subjected to a series of eccentric contractions showed sarcomeres with A bands displaced toward one half-sarcomere, leaving no overlap in the other half. Adjacent regions often looked normal. These results are all in agreement with the predictions of the nonuniform stretch of sarcomeres hypothesis. PMID- 8214036 TI - Autocrine control of wound repair by insulin-like growth factor I in cultured endothelial cells. AB - The repair process of the vascular endothelium is modulated by growth factors from both endogenous (within the vessel wall) and exogenous (blood borne) sources. We utilized a tissue culture model of endothelial wounding to gain further insight into the potential autocrine control of proliferation during wound repair. Cultured porcine aortic endothelial monolayers were mechanically wounded by passing a 7-mm sterile glass rod over the surface of the culture. Proliferation at the wound edge was quantified using [3H]thymidine autoradiography. In wounded cultures incubated in media supplemented with 10% fetal calf serum, 81 +/- 2% of the nuclei at the wound edge were labeled. When the cultures were incubated in serum-free media, proliferation at the wound edge was only slightly diminished with 65 +/- 3% (P < 0.05) of the cells labeled. These findings raise the possibility that there is a significant contribution from autocrine growth factors to endothelial wound repair. To evaluate the potential role of insulin-like growth factor I (IGF-I) in the wound repair process, we used a radioimmunoassay to measure IGF-I secretion. Wounded cultures exhibited a 187 +/- 58% increase in IGF-I production when compared with nonwounded cultures (P < 0.05). To determine the extent to which endogenous IGF-I mediates the proliferative response of endothelial cell monolayers to wounding, wounded cultures were incubated with inactivating concentrations of IGF-I antibody. When IGF-I antibody was present in the culture media, only 26 +/- 3% of the nuclei at the wound edge were labeled with [3H]thymidine (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214037 TI - Thrombin-induced mitogenesis of vascular SMC is partially mediated by autocrine production of PDGF-AA. AB - Previous studies have shown that alpha-thrombin (Thr) is a mitogen for cultured smooth muscle cells (SMC), but controversy exists concerning mechanisms of growth stimulation. The purpose of these studies was to determine whether autocrine production of platelet-derived growth factor-AA (PDGF-AA) mediated Thr-induced SMC mitogenesis. SMC derived from aortae of Sprague-Dawley rats were grown to confluence, growth arrested in serum-free medium, and treated. Conditioned medium (CM) was harvested by adding bovine serum albumin as a carrier and hirudin to neutralize residual Thr. Results demonstrated that CM from Thr-treated SMC (Thr CM) had increased mitogenic activity compared with control CM (Cnt CM) and that PDGF-AA levels were increased 12-fold in Thr CM compared with Cnt CM. The excess mitogenic activity in Thr CM was markedly inhibited by PDGF-AA-neutralizing antibodies. Cotreatment with Thr and PDGF-AA-neutralizing antibodies resulted in a 30% decrease in Thr-induced [3H]thymidine incorporation. These results demonstrate that autocrine production of PDGF-AA partially mediated Thr-induced SMC mitogenesis. PMID- 8214038 TI - ATP-sensitive K+ channels in rat aorta and brain microvascular endothelial cells. AB - The endothelium plays an important role in the modulation of vascular tone and blood cell activation. Extensive work has demonstrated that the release of endothelium-derived relaxing factor (EDRF) from the endothelium is evoked by a number of physical and chemical stimuli requiring Ca2+. Because endothelial cells do not express voltage-dependent Ca2+ channels, Ca2+ influxes following receptor activation may be facilitated by cell hyperpolarizations mediated by the activation of K+ conductances. There has been recent interest in the role of ATP sensitive K+ channels (KATP) suggesting that KATP may play a role in the regulation of blood flow. We have investigated the electrophysiological properties of an ATP-sensitive K+ conductance in whole cell and membrane patches from rat aorta and brain microvascular endothelial cells. Whole cell as well as single-channel currents were increased by either intracellular dialysis of ATP or application of glucose-free/NaCN (2 mM) solutions. Both currents were reversibly blocked by glibenclamide (1-100 microM). The KATP channel opener pinacidil (30 microM) caused activation of an outward current in the presence of physiological intracellular ATP concentrations. In inside-out patches, 10 microM-1 mM ATP invariably caused a dramatic decrease in channel activity. We conclude that both rat aorta and brain microvascular endothelial cells express KATP channels. KATP may play a role in the regulation of endothelial cell resting potential during impaired energy supply and therefore modulate EDRF release and thus cerebral blood flow. PMID- 8214039 TI - Adaptations in myosin heavy chain expression and contractile function in dystrophic mouse diaphragm. AB - The X chromosome-linked muscular dystrophic (mdx) mouse lacks the subsarcolemmal protein dystrophin and thus represents a genetic homologue of human Duchenne muscular dystrophy. The present study examined alterations in diaphragm contractile properties and myosin heavy chain (MHC) expression in young (3-4 mo) and old (22-24 mo) control and mdx mice. In young mdx mice, maximum isometric tension (Po) was reduced to 50% of control values. An increase in fibers coexpressing types I (slow) and IIa MHC as well as regenerating fibers expressing embryonic MHC occurred, whereas IIx/b fibers were decreased. In the old mdx group, Po underwent a further reduction to 25% of control, and there was a slowing of twitch kinetics along with markedly increased diaphragm endurance. These changes were associated with an approximate sevenfold increase in type I MHC fibers and virtual elimination of the IIx/b fiber population; there was no detectable embryonic MHC expression. We conclude that the mdx diaphragm responds to progressive muscle degeneration with transition to a slower phenotype associated with reduced power output and augmented muscle endurance. In the setting of progressive muscle fiber destruction, these changes may help preserve contractile function and promote greater survival of remaining muscle fibers by decreasing cellular energy requirements. PMID- 8214040 TI - Single fiber analyses of type IIA myosin heavy chain distribution in hyper- and hypothyroid soleus. AB - The objectives of this study were to 1) examine the effect of hypo- and hyperthyroidism (triiodothyronine treatment) on the distribution of type IIA myosin heavy chain (MHC) in the soleus at the single fiber level and 2) correlate changes in the single fiber distribution of type IIA MHC with the maximal shortening velocity of whole skeletal muscle. The presence of the type IIA MHC in single fibers was determined using a monoclonal antibody reactive to the type IIA MHC and quantified with a Meridian ACAS 570 interactive laser cytometer. The findings of this study demonstrate that 1) hyperthyroidism significantly increases the relative number of muscle fibers that express type IIA MHC, 2) not all type I fibers are capable of expressing fast type IIA MHC under hyperthyroid conditions, and 3) there is a high correlation between maximal shortening velocity and the relative number of type IIA fibers. This latter observation suggests that the maximal shortening velocity of whole skeletal muscle may not be solely determined by its fastest fiber(s) but rather by the relative proportion of fibers expressing fast type IIA MHC. PMID- 8214041 TI - Imaging of reconstituted biological channels at molecular resolution by atomic force microscopy. AB - Using atomic force microscopy (AFM), we obtained high-resolution surface images of the bacterial outer membrane channels Escherichia coli OmpF porin and Bordetella pertussis porin that were reconstituted in artificial bilayer membranes as two-dimensional crystalline arrays. These porins were chosen because they are among the most extensively studied proteins of this type and are known for their well-defined crystalline nature in the native membrane. Such reconstituted membrane proteins are ideal specimens to assess the suitability and resolution of AFM for imaging biomembranes and associated proteins. Although OmpF porin often showed a mixed pattern of rectangular and hexagonal arrays with approximately 8.4 x 9.8- and approximately 7.2-nm-spacings, respectively, B. pertussis porin showed mostly a rectangular pattern with an approximately 7.9 x 13.8-nm spacing. The packing patterns of the E. coli OmpF porin in the membrane are very close to those found in electron-microscopic studies. When B. pertussis porin was imaged in a buffer solution, its trimeric subunits were apparently resolved, and the surface of each monomer revealed beadlike structures. This is the first report of such a high-resolution structural analysis of B. pertussis porin by any imaging method. We also imaged the lipid bilayer itself as an internal control for imaging and to further ascertain the resolution. Individual polar head groups of bilayer lipid molecules were resolved, suggesting the intrinsic resolution of AFM for bioimaging. PMID- 8214042 TI - Glucose metabolism during fasting through human pregnancy: comparison of tracer method with respiratory calorimetry. AB - Glucose turnover and glucose oxidation were quantified in six normal pregnant women serially throughout pregnancy, using [U-13C]glucose tracer in combination with open-circuit indirect respiratory calorimetry. Five normal nonpregnant women were studied for comparison. With advancing gestation and increase in maternal body weight, there was a proportionate increase in the rate of appearance (Ra) of glucose so that Ra expressed per kilogram body weight did not change from the first to third trimester. The tracer measured rate of glucose oxidation expressed per kilogram body weight also did not change significantly throughout pregnancy. Oxygen consumption (VO2) in pregnant subjects did not differ from that in nonpregnant subjects. However, the respiratory exchange ratio (RER) increased significantly during pregnancy (0.88 +/- 0.53 3rd trimester and 0.76 +/- 0.50 nonpregnant, P < 0.01). The estimated contribution of carbohydrate to VO2 measured by respiratory calorimetry was greater than that measured by the tracer method. This discrepancy became wider as the respiratory quotient increased in late pregnancy. These data suggest that maternal glucose metabolism adjusts throughout pregnancy to meet the increased demands of the conceptus. The discrepancy between tracer method and respiratory calorimetry was probably due to the contribution of (fetal) lipogenesis and (maternal) gluconeogenesis to RER. PMID- 8214043 TI - Do nonesterified fatty acids regulate skeletal muscle protein turnover in humans? AB - We examined whether elevated plasma nonesterified fatty acid (NEFA) levels exert a direct effect on protein metabolism by measuring [2H5]phenylalanine skeletal muscle exchange and whole body turnover. [2H5]phenylalanine was infused (0.5 mg.kg-1 x h-1) for 300 min in seven healthy subjects on two occasions. Intralipid (10%; 30 ml/h) or 0.154 mol/l NaCl was infused in random order from 120 min. Measurements were taken during basal (90-120 min) and infusion (270-300 min) periods. Intralipid infusion increased plasma NEFA levels [1.31 +/- 0.13 vs. 0.49 +/- 0.05 (SE) mmol/l; P < 0.05] and forearm NEFA uptake [45 +/- 76 vs. -51 +/- 44 nmol . 100 ml forearm-1 x min-1; P < 0.05]. Serum insulin and blood ketone body levels were similar with the two treatments. Elevated plasma NEFA levels were associated with a comparable decrease in forearm phenylalanine uptake (11 +/- 2 vs. 17 +/- 2 nmol x 100 ml forearm-1 x min-1; lipid vs. control, P < 0.05) and release (20 +/- 2 vs. 26 +/- 3 nmol x 100 ml forearm-1 x min-1; lipid vs. control, P < 0.05). However, there were no significant changes in net forearm phenylalanine exchange and whole body phenylalanine turnover. Therefore, elevated plasma NEFA levels were associated with a comparable decrease in the rates of skeletal muscle protein synthesis and breakdown but did not appear to influence overall protein balance, as assessed using [2H5]phenylalanine. PMID- 8214044 TI - Pressor doses of angiotensin II increase insulin-mediated glucose uptake in normotensive men. AB - The effect of pressor doses of angiotensin II infused intravenously on insulin mediated glucose uptake was determined in normotensive men. A 3-h hyperinsulinemic euglycemic clamp was employed in 14 normotensive subjects to determine insulin-mediated glucose uptake with or without an infusion of angiotensin II (approximately 15 ng.kg-1.min-1), which increased blood pressure by 20/15 mmHg (systolic/diastolic). Addition of angiotensin II increased whole body glucose uptake by 15% (9.2 +/- 0.5 vs. 10.8 +/- 0.8 mg.kg-1 x min-1; P = 0.011), and glucose oxidation (determined by indirect calorimetry) by 25% (4.0 +/ 0.3 vs. 4.9 +/- 0.4 mg.kg-1 x min-1; P < 0.05) over insulin alone. There was no significant increase in hepatic glucose output during angiotensin II infusion (2.2 +/- 0.1 vs. 2.4 +/- 0.1 mg.kg-1 x min-1; P = NS). We conclude that angiotensin II in pressor doses increases insulin-mediated glucose disposal and oxidation. The mechanism for this may involve a redirection of blood flow into skeletal muscle during angiotensin II infusion or a direct biochemical action of angiotensin II. Although performed in lean normotensive subjects, these results cast doubt on a significant role for angiotensin II in the insulin resistance associated with essential hypertension. PMID- 8214045 TI - Second messenger signaling of PTH- and PTHRP-stimulated osteoclast-like cell formation from hemopoietic blast cells. AB - The second messenger signaling mechanisms of parathyroid hormone (PTH)- and PTH related peptide (PTHRP)-stimulated osteoclast-like cell formation were investigated in mouse hemopoietic blast cells that possessed PTH binding sites. Human (h) PTH-(1-34) or hPTHRP-(1-34) resulted in a dose-dependent stimulation of tartrate-resistant acid phosphatase-positive multinucleated cells (MNC) formation. Pretreatment with [Nle8,18Tyr34]hPTH-(3-34) significantly blocked hPTH (1-34)- and hPTHRP-(1-34)-stimulated MNC formation. Dibutyryladenosine 3',5' cyclic monophosphate (10(-4) M) and forskolin (10(-5) M) as well as the stimulatory diastereoisomer of adenosine 3',5'-cyclic phosphorothioate (Sp cAMPS), a direct activator of adenosine 3',5'-cyclic monophosphate (cAMP) dependent protein kinase (PKA) (10(-4) M), stimulated MNC formation, and Rp cAMPS, an inhibitor of PKA activation (10(-4) M), almost completely inhibited MNC formation stimulated by the aforementioned agents but not by 1,25 dihydroxyvitamin D3. Moreover, Rp-cAMPS significantly blocked PTH- and PTHRP stimulated MNC formation. Treatment with calcium ionophores (10(-8) and 10(-7) M) and phorbol 12-myristate 13-acetate, a protein kinase C (PKC) activator (10(-8) to 10(-6) M), but not 4 alpha-phorbol 12,13-didecanoate, a phorbol incapable of activating PKC, stimulated MNC formation. Two PKC inhibitors [1-(5 isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride and staurosporine] equally blocked PTH- and PTHRP-stimulated MNC formation. The combined pretreatment with Rp-cAMPS and PKC inhibitors completely blocked PTH- and PTHRP stimulated MNC formation. Present findings indicate that the activation of PKA and PKC is directly linked to PTH- and PTHRP-stimulated osteoclast-like cell formation from hemopoietic blast cells. PMID- 8214046 TI - In vitro lipid synthesis in human adipose tissue from three abdominal sites. AB - The association between abdominal deposition of adipose tissue and morbidities accompanying obesity may be related to high rates of free fatty acid release from enlarged intra-abdominal stores. To investigate cellular mechanisms that might contribute to enlargement of intra-abdominal adipocytes, lipolysis, triacylglycerol (TG), and diacylglycerol (DG) synthesis from [14C]glucose was measured in abdominal subcutaneous, omental, and mesenteric adipose tissue from severely obese women and men. Subcutaneous adipose tissue from women showed the highest rates of TG synthesis compared with the intra-abdominal site, or any site in men. isoproterenol stimulated TG synthesis more in intra-abdominal than subcutaneous adipose tissue. In the basal state, intra-abdominal adipose tissue from both men and women showed rates of [14C]DG accumulation approximately 50% total [14C]acylglyceride accumulation, whereas, in subcutaneous adipose tissue, [14C]DG accumulation was approximately 25% of total. Basal lipolysis was lower in intra-abdominal than subcutaneous adipocytes. Stimulation of lipolysis reduced [14C]DG accumulation more in intra-abdominal than subcutaneous adipose tissue. Low rates of acylglyceride synthesis in intra-abdominal adipocytes may prevent accumulation of large intra-abdominal fat stores in women. PMID- 8214047 TI - Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. AB - Stable isotope tracers and indirect calorimetry were used to evaluate the regulation of endogenous fat and glucose metabolism in relation to exercise intensity and duration. Five trained subjects were studied during exercise intensities of 25, 65, and 85% of maximal oxygen consumption (VO2max). Plasma glucose tissue uptake and muscle glycogen oxidation increased in relation to exercise intensity. In contrast, peripheral lipolysis was stimulated maximally at the lowest exercise intensity, and fatty acid release into plasma decreased with increasing exercise intensity. Muscle triglyceride lipolysis was stimulated only at higher intensities. During 2 h of exercise at 65% VO2max plasma-derived substrate oxidation progressively increased over time, whereas muscle glycogen and triglyceride oxidation decreased. In recovery from high-intensity exercise, although the rate of lipolysis immediately decreased, the rate of release of fatty acids into plasma increased, indicating release of fatty acids from previously hydrolyzed triglycerides. We conclude that, whereas carbohydrate availability is regulated directly in relation to exercise intensity, the regulation of lipid metabolism seems to be more complex. PMID- 8214048 TI - Regulation of glucose transporter and hexokinase II expression in tissues of diabetic rats. AB - Glucose transport and phosphorylation are decreased in muscle and adipose tissue in diabetes mellitus. The glucose transporter GLUT-4 and hexokinase II (HK II) are the main isoforms of proteins involved in glucose transport and phosphorylation in insulin-sensitive tissues, adipose tissue, skeletal muscle, and heart. The molecular mechanisms responsible for the decrease of glucose transport and phosphorylation have been studied during the first 3 days after streptozotocin (STZ) administration in adult male Wistar rats. GLUT-4 mRNA and protein and HK II mRNA and enzyme activity were measured. After the injection of STZ (30 h), GLUT-4 and HK II mRNAs were decreased to 10 +/- 1 and 20 +/- 3% that found in nondiabetic rats, respectively; they remained at these low levels for 72 h. Normalization of the blood glucose level by phlorizin infusion did not restore GLUT-4 and HK II mRNA concentrations to normal. In contrast, normalization of the blood glucose level by physiological infusion of insulin resulted in a total normalization of GLUT-4 and HK II mRNA concentrations. When insulin therapy was stopped, GLUT-4 and HK II mRNA and protein concentrations fell in 6 h to 40 and 20% of control levels, respectively. Minimal changes of GLUT-4 and HK II mRNA, and of HK II activity, were observed in skeletal muscle and heart of diabetic rats. We conclude that GLUT-4 and HK II mRNA are coordinately expressed in white adipose tissue. They are rapidly affected by an acute decrease of the plasma insulin concentrations but are not modified by hyperglycemia. In contrast, skeletal muscle and heart GLUT-4 and HK II mRNA are not greatly affected by short term diabetes. PMID- 8214049 TI - Leucine metabolism in lactating and dry goats: effect of insulin and substrate availability. AB - Early lactating goats show insulin resistance with respect to extramammary glucose utilization. However, much less is known about the two major factors, insulin and plasma amino acid concentration, that regulate protein metabolism in lactating goats. To examine this question, the in vivo effect of acute insulin was studied in goats during early lactation (12-31 days postpartum), midlactation (98-143 days postpartum), and the dry period (approximately 1 yr postpartum). Insulin was infused (at 0.36 or 1.79 nmol/min) under euglycemic and eukaliemic clamps. In addition, appropriate amino acid infusion was used to blunt insulin induced hypoaminoacidemia or to create hyperaminoacidemia and maintain this condition under insulin treatment. Leucine kinetics were assessed using a primed continuous infusion of L-[1-14C]-leucine, which started 2.5 h before insulin. In all animals the insulin treatments failed to stimulate the nonoxidative leucine disposal (an estimate of whole body protein synthesis) under both euaminoacidemic and hyperaminoacidemic conditions. Thus, in goat as well as humans, infusion of insulin fails to stimulate protein synthesis even when combined with a substantially increased provision of amino acids. In contrast, insulin treatments caused a dose-dependent inhibition of the endogenous leucine appearance (an estimate of whole body protein degradation). Under euaminoacidemia the initial slope from the plot of the endogenous leucine appearance as a function of plasma insulin (an insulin sensitivity index) was steeper during early lactation than when compared with the dry period. A similar trend occurred during midlactation but not to any significant degree. These differences were abolished under hyperaminoacidemia. It was concluded that the ability of physiological insulin to inhibit protein degradation was improved during lactation, demonstrating a clear cut dissociation between the effects of insulin on protein and glucose metabolism. This adaptation no doubt may provide a mechanism to save body protein. PMID- 8214050 TI - Angiotensin II is the mediator of the increase in hepatic angiotensinogen synthesis after bilateral nephrectomy. AB - The present study investigated the hypothesis that the increase in plasma angiotensinogen after nephrectomy is mediated by endogenous renin and angiotensin (ANG) II. Rats were divided into control, nephrectomy, or nephrectomy plus adrenalectomy groups. In addition, similar cohorts were divided as just mentioned and then given either atenolol (selective beta 1-adrenoceptor inhibitor that prevents renin release) or Dup-753 [ANG II (AT1) receptor antagonist]. The plasma angiotensinogen levels increase approximately fivefold after 24 h in nephrectomized rats. Pretreatment with atenolol blunted this increase. A significant reduction was observed 4 h (P < 0.05) and 8 h (P < 0.005) after surgery. Dup-753 nearly abolished the increase in angiotensinogen plasma levels. After pretreatment with Dup-753, significantly higher angiotensinogen levels (P < 0.005) were found only after 24 h. Nephrectomy plus adrenalectomy also blunted the rise in plasma angiotensinogen. A significant increase in angiotensinogen plasma levels could only be observed after 8 h (P < 0.005) and 12 h (P < 0.005) but not after 24 h. Atenolol further reduced this increase. After atenolol pretreatment, significantly higher angiotensinogen levels could only be observed after 12 h (P < 0.05). Dup-753 completely abolished the increase of plasma angiotensinogen after nephrectomy plus adrenalectomy. In anesthetized control rats at time 0 the plasma ANG I levels were 0.7 nM. Pretreatment with atenolol decreased the ANG I values by 30%, whereas Dup-753 caused a sixfold increase in plasma ANG I levels in the control rats at time 0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214051 TI - Effects of exercise training on muscle GLUT-4 protein content and translocation in obese Zucker rats. AB - The rates of muscle glucose uptake of trained (TR) and untrained (UT) obese Zucker rats were assessed by hindlimb perfusion under basal conditions (no insulin) in the presence of a maximally stimulating concentration of insulin (10 mU/ml) and after muscle contraction elicited by electrical stimulation of the sciatic nerve. Perfusate contained 28 mM glucose and 7.5 microCi/mmol of 2-deoxy D-[3H]glucose. Muscle GLUT-4 concentration was determined by Western blot analysis and expressed as a percentage of a heart standard. The rates of insulin stimulated glucose uptake were significantly higher in the plantaris, red gastrocnemius (RG), and white gastrocnemius (WG), but not the soleus or extensor digatorum longus (EDL) of TR compared with UT rats. After muscle contraction the rates of glucose uptake in the TR rats were significantly higher in the soleus, plantaris, and RG. TR rats had significantly higher GLUT-4 protein concentration and citrate synthase activity than the UT rats in the soleus, plantaris, RG, and WG. Basal plasma membrane GLUT-4 protein concentration of TR rats was 144% above UT rats (P < 0.01). Stimulation by insulin and contraction resulted in a significant increase in plasma membrane GLUT-4 protein concentration in UT rats only. However, plasma membrane GLUT-4 protein concentration in insulin- and contraction-stimulated TR rats remained 53% and 30% greater than that of UT rats, respectively (P < 0.05). Exercise training did not alter basal, insulin-, or contraction-stimulated GLUT-4 functional activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214052 TI - Aldose reductase gene expression and osmotic dysregulation in cultured human retinal pigment epithelial cells. AB - A "compatible osmolyte hypothesis" proposes that intracellular nonionic organic osmolytes such as sorbitol, myo-inositol, taurine, betaine, and glycerophosphorylcholine respond coordinately to changes in external osmolality, thereby maintaining the intracellular ionic milieu. Osmoregulation may be the primary physiological function of aldose reductase, which catalyzes the conversion of glucose to sorbitol. Glucose-induced sorbitol accumulation in isosmotic hyperglycemic states is associated with compensatory depletion of myo inositol and taurine. Because such depletion may predispose to chronic diabetic complications, the relationship between osmolyte shifts and aldose reductase gene expression was studied in two human retinal pigment epithelial cell lines, one exhibiting osmoregulated and the other high basal aldose reductase gene expression. High basal expression of the aldose reductase gene was associated with rapid sorbitol accumulation and myo-inositol depletion in response to hyperglycemic (20 mM) concentrations of glucose. Myo-inositol and sorbitol behaved as compensating intracellular osmolytes by accumulating markedly in response to hyperosmolality (300 mM mannitol). Thus the pattern of response of myo-inositol to hyperglycemic and hyperosmotic levels of glucose and mannitol was related to the degree of basal aldose reductase gene expression, which may therefore influence the development of diabetic complications. PMID- 8214054 TI - Atrial natriuretic peptides are present throughout the plant kingdom and enhance solute flow in plants. AB - The present investigation was designed to 1) determine if atrial natriuretic-like peptides are present throughout the plant kingdom and 2) to determine if these peptides increase the flow of solute and/or water upward to leaves and flowers of plants. The 126-amino acid prohormone of atrial natriuretic factor (proANF)-(1 30), proANF-(31-67), and atrial natriuretic factor (ANF)-like peptides were present in the roots, stems, leaves, and flower petals of the more highly developed plants (Tracheophyta), with their highest concentrations being: Florida beauty > buddhist pine > Boston fern > rose = geranium = resurrection plant or club moss > Moses-in-the-cradle > Florida coontie. These peptides were also present in Bryophata (plants without vascular tissue or roots) and even in Euglena, flagellated chlorophyll-containing plants without leaves, stems, or roots. proANF-(1-30), proANF-(31-67), and proANF-(79-98) but not ANF (each at < 5.9 pg/ml) significantly increased (P < 0.001) the flow of colored water up stems, coloring their flowers 15-35 min earlier than the other one-half of the same flowers without exogenous peptide addition. These same peptides increased the rate of transpiration (i.e., loss of water from the leaves) and the absorption of solutions. High-performance gel permeation chromatography revealed that proANF-(1-30), proANF-(31-67), and ANF extracted from plants are very similar to their pure synthetic human sequences, with elution profiles and molecular weights of the plant extracts duplicating those of the pure synthetic peptides. PMID- 8214053 TI - Immunolocalization of GLUT-1 glucose transporter in rat skeletal muscle and in normal and hypoxic cardiac tissue. AB - We compared the expression and cell-type localization of GLUT-1 mRNA and protein between cardiac and skeletal muscle of normal rats. Also, since we recently showed that cardiac GLUT-1 is upregulated in rats exposed to hypobaric hypoxia, we examined the cellular localization of GLUT-1 in cardiac tissue of normal and hypoxic rats. Confocal light microscopy and double immunofluorescent labeling revealed intense localization of GLUT-1 around neurofilament immunoreactivity within gastrocnemius muscle consistent with the previously described localization of large amounts of GLUT-1 in perineurial sheaths of skeletal muscle. However, using the same methods, we were unable to visualize GLUT-1 adjacent to nerve fibers in numerous sections of right or left ventricles or atria. Compared with skeletal myoctes, however, GLUT-1 immunofluorescence among cardiomyocytes was much more intense, particularly along the plasma membrane and especially intercalated discs. GLUT-1 immunofluorescence was also seen within the walls of arterioles within the heart. The predominant localization of GLUT-1 expression to cardiomyocytes in heart tissue was confirmed by in situ mRNA hybridization to digoxigenin-conjugated GLUT-1 cDNA. Northern blot analysis demonstrated that GLUT 1 mRNA was increased severalfold in the cardiac tissues compared with skeletal muscle. Although we detected GLUT-1 protein by immunoblotting of detergent extracts of the heart, we could not detect GLUT-1 in similar extracts of skeletal muscle. The cell type distribution of GLUT-1 in hearts of hypoxic rats was not different by immunohistochemistry from normals. These data indicate that 1) the cell-type distribution of GLUT-1 in the heart differs markedly from that in skeletal muscle. GLUT-1 in cardiac tissue, unlike skeletal muscle, is predominantly expressed within myocytes. 2) Cardiac GLUT-1 is not located along nerve fibers. 3) GLUT-1 mRNA and protein levels in cardiac tissue are considerably greater than in skeletal muscle. 4) The hypoxia-induced increase in cardiac GLUT-1 that we previously reported must occur within cardiomyocytes. PMID- 8214055 TI - Onset of excess fat deposition in Zucker rats with and without decreased thermogenesis. AB - To study the first stages of excess fat deposition in Zucker rats, we artificially fed littermates with identical amounts of milk from 4 to 15-16 days of age while continuously recording oxygen consumption (VO2) and deep body temperature. Under intermittent cold loads simulating the periodic thermoregulatory stimulation experienced in the nest, differences between the amounts of body fat deposited by artificially reared fatty (fa/fa) and lean (Fa/ ) pups were as large as those seen in mother-reared pups. The decreased VO2 of the cold-reared fatty pups could account for 90-100% of their extra fat deposition. At thermoneutrality, 16-day-old littermates reared with low feeding rates showed small but significant genotype differences in body fat that were not energetically accounted for by differences in VO2 or lean body mass. Slightly but significantly lower fecal energy losses indicated that differences in resorption might account for the positive energy balance of thermoneutrally reared fa/fa pups. Reduced energy expenditure thus efficiently fuels excess fat deposition but is not essential for the onset of excess fat deposition in fa/fa pups. Other factors than reduced sympathetic activation of brown adipose tissue must be considered as a primary cause for the development of fa/fa obesity. PMID- 8214056 TI - Effect of hepatic nerves on disposition of an intraduodenal glucose load. AB - We examined the disposition of a continuous 4-h intraduodenal glucose infusion (8 mg.kg-1 x min-1, labeled with [1-13C]glucose and [3-3H]glucose) in nine conscious hepatic-denervated dogs. Cumulative net hepatic uptakes (in grams of glucose equivalents) were 13.7 +/- 2.5 glucose, 3.1 +/- 0.6 gluconeogenic amino acids, and 0.8 +/- 0.1 glycerol. Net hepatic glycogen synthesis totalled 11.0 +/- 0.9 g, 55-62% via the direct pathway. All values were similar to those in hepatic innervated dogs. Glycogen synthase activity and rate of glycogen synthesis were positively correlated (r2 = 0.913, P < 0.05). Variability in net hepatic glycogen synthesis and the mass of glycogen synthesized via the indirect pathway was reduced in hepatic-denervated dogs (P < 0.05). In conclusion, the glycemic response and rate of net glycogen synthesis during an intraduodenal glucose infusion was no different in hepatic-denervated and -innervated dogs. Net hepatic glucose uptake was sufficient to account for all net hepatic glycogen synthesis and lactate production, consistent with an intrahepatic source of gluconeogenic precursors for glycogen synthesis via the indirect pathway. Hepatic nerves appear responsible for much of the variability in net hepatic glycogen synthesis and in the mass of glycogen synthesized via the indirect pathway in normal dogs. PMID- 8214057 TI - Alanine umbilical uptake, disposal rate, and decarboxylation rate in the fetal lamb. AB - Fetal plasma alanine disposal rate (DR) and decarboxylation rate were measured at 132 +/- 1 days gestation in nine fetal lambs infused with L-[1-14C]alanine via a brachial vein. In five experiments, L-[1-13C]alanine was added to the infusate. Using L-[1-14C]alanine, we found mean DR to be 15.5 +/- 1.8 mumol.min-1 . kg-1. DR was significantly correlated to both arterial plasma alanine and whole blood lactate concentrations. Placental uptake of fetal plasma alanine accounted for 19 +/- 4% of DR. Fetal and placental production of CO2 from the first carbon of alanine were 61 +/- 2 and 16 +/- 2% of DR, respectively, for a total uterine excretion of 77 +/- 3%. Net alanine flux from placenta to fetus was 5.2 +/- 0.5 mumol.min-1 x kg-1, which was less than fetal plasma alanine decarboxylation (9.4 +/- 1.2 mumol.min-1 x kg-1) plus fetal alanine accretion (2.4 mumol.min-1 x kg 1). Utilizing L-[1-13C]alanine, we found DR to be 14.2 +/- 0.8 mumol.min-1 x kg 1, not significantly different from the 14C data. We conclude that both the umbilical uptake of alanine from the placenta and fetal alanine synthesis contribute to fetal alanine supply and that oxidation is the main route of fetal plasma alanine disposal. PMID- 8214058 TI - Metabolic and thermogenic effects of lactate infusion in humans. AB - Lactate has been suggested to interfere with intermediary metabolism by restricting both lipolysis and glucose utilization. To test this hypothesis, in paired studies in healthy volunteers, sodium lactate (25 mumol.min-1 x kg-1) or saline was infused for 1 h in the fasting state and during 2 h of euglycemic (4.75 mM) hyperinsulinemia (approximately 400 pmol/l). Hyperlactatemia (approximately 2 mM) had no inhibitory effect on fasting free fatty acid or glycerol levels nor did it alter the suppressive action of insulin on these substrates. Likewise, sodium lactate infusion did not influence hepatic glucose production ([3-3H]glucose technique) or its suppression by insulin. During the clamp, hyperlactatemia was associated with a small increase in whole body glucose disposal (34.9 +/- 4.1 vs. 30.3 +/- 3.7 mumol.min-1 x kg-1, P < 0.05) with no major change in the pattern of substrate (carbohydrate vs. lipid) oxidation. By simultaneously measuring arteriovenous gradients across the deep tissues of the forearm (forearm technique), it was found that hyperlactatemia did not impede insulin-mediated glucose uptake; furthermore, it could be estimated that muscle tissues were responsible for the disposal of roughly one-fifth of the lactate load. Whole body energy expenditure was stimulated above the level achieved with hyperinsulinemia when lactate was also infused. Thus, under the present experimental conditions, physiological hyperlactatemia did not interfere with lipolysis, hepatic glucose production, or whole body or forearm muscle glucose utilization, or with insulin action on these processes, and was accompanied by a strong thermogenic effect. PMID- 8214059 TI - A minimal model for human whole body cholesterol metabolism. AB - Important work by others has shown that human whole body cholesterol metabolism can be described by a three-compartment model computed from plasma cholesterol specific activity after an intravenous infusion of labeled cholesterol. However, some parameters of that model cannot be estimated precisely [coefficient of variation (CV) 15-19% after 40 wk of follow-up], making its use in routine clinical investigation difficult. On the other hand, a simpler two-compartment model can be calculated with excellent precision from only 10 wk of data (CV 2 8%), but its parameters are inaccurate (for example, the size of the central pool is overestimated by 20%, and the rate constant for fractional excretion of cholesterol from the body is underestimated by 15%). Thus both three-compartment and two-compartment models of cholesterol turnover have important limitations. An alternative is provided by a minimal model that takes advantage of the increased precision expected in the solution of models with fewer parameters. A three compartment structure is used, but only four (rather than 6 or more) parameters are calculated: the mass of the rapidly mixing central cholesterol compartment, the fractional rate of cholesterol elimination from the body, and the average forward and reverse rate constants for cholesterol transfer between the rapid compartment and both slower compartments. Each of these parameters can be determined unambiguously (without the need to use a minimum or maximum estimate), accurately (mean values within 2% of theory), and with precision (CV 3 13%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214060 TI - 5'- and 5-deiodinase activities in adult rat cecum and large bowel contents inhibited by intestinal microflora. AB - Enzymatic mechanisms for deiodination of 3,5,3'-triiodothyronine or thyroxine in the phenolic ring (5'-deiodinase) or tyrosyl ring (5-deiodinase) are found in cells of many organs, including the intestinal wall. Deiodinases are highly active in intestinal tissue of developing rat fetuses and relatively inactive in adult intestinal cells, but little is known about these systems in the luminal contents of intestines. We have found both 5- and 5'-deiodinase activities in adult rat intestinal contents and have shown that their expression is inhibited by resident intestinal microflora, which are normally present in the adult but not in the fetus, possibly because they are bound by intestinal bacteria in the adult. PMID- 8214061 TI - On the coupling of membrane digestion with intestinal absorption of sugars and amino acids. AB - An hypothesis is advanced to account for the large paracellular component of absorption of nutrients by the small intestine. High concentrations of hexoses and amino acids in the immediate vicinity of transporters and cell junctions are generated by membrane-bound saccharases and peptidases. After saturation of membrane carriers, the concentrations of monomers in the microenvironment increase until paracellular plus transcellular absorption equals rates of formation. During hydrolysis of maltose, the concentration of glucose at which rates of absorption and formation are equal is 200-300 mM, and at these concentrations paracellular transport accounts for 60-80% of total absorption. Transcellular concentrative transport provides the force for osmotic flow and at the same time triggers contraction of perijunctional actomyosin, thereby increasing transjunctional coefficients of osmotic flow and solvent drag. Paracellular absorption requires no oxidative energy other than that required to maintain the transjunctional concentration gradient and to energize contraction of cytoskeletal elements controlling junctional permeability and functional surface of lateral membranes. Almost all glucose generated by membrane hydrolysis is absorbed, but some may diffuse from high concentration in the microenvironment to the lumen thus accounting for the small amounts of free glucose found in macrosamples of chyme. Unstirred layers adjacent to the brush border retard backdiffusion to lumen, thus maintaining high concentrations for passive paracellular absorption. Coupling of membrane digestion with paracellular transport provides almost perfect matching of absorption to digestive loads because transport by solvent drag is proportional to concentration at cell junctions and this in turn is proportional to rate of hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214062 TI - Nitric oxide generators and cGMP stimulate mucus secretion by rat gastric mucosal cells. AB - The effect of nitric oxide (NO) donors on the release of mucus from a suspension of isolated gastric cells was investigated by using an enzyme-linked immunosorbent assay for rat gastric mucin. Isosorbide dinitrate (ISDN, 0.1-2 mM) produced a dose-related stimulation of mucus secretion, without affecting the viability of the isolated cells as determined by trypan blue exclusion or acid phosphatase release. In a comparable concentration range to that stimulating mucus release, ISDN elevated the guanosine 3',5'-cyclic monophosphate (cGMP) content of cell suspensions enriched with mucous cells. The nitrosothiol S nitroso-N-acetylpenicillamine (0.3 mM), which spontaneously liberates NO, likewise stimulated mucus release, and this action was blocked by 10 microM oxyhemoglobin, which scavenges NO. Nitroprusside (1 mM), dibutyryl cGMP (0.01-1 mM), and the cGMP phosphodiesterase inhibitor M & B 22948 (0.1 mM) also increased mucus release. Thus generators of NO stimulate mucus secretion by rat gastric mucosal cells, which may reflect the elevation of intracellular cGMP. These findings, along with the presence of NO synthase in the gastric epithelial cells, suggest an effector role for NO in mediation of gastric mucus release. PMID- 8214063 TI - Stimulation of Cl permeability in colonic crypts of Lieberkuhn measured with a fluorescent indicator. AB - Crypts of Lieberkuhn were isolated from rabbit distal colon and the halide sensitive dye 6-methoxy-N-[3-sulfopropyl]quinolinium was used to monitor changes in cell Cl by fluorescence microscopy. Distal colon from rabbits actively secretes Cl and K when stimulated with prostaglandin (PG) E2 but secretes only K in response to epinephrine. The secretagogues PGE2 and epinephrine each produced transient decreases of the apparent cell Cl concentration in about one-half of the crypt cells. Permeability to Cl was assessed by brief substitutions with gluconate or Br in the bath. After stimulation of secretion by PGE2 or epinephrine, Cl efflux and Br influx were increased but only in the cells that exhibited the decrease in cell Cl at the onset of stimulation. Although Cl efflux during gluconate substitution was stimulated similarly with either PGE2 or epinephrine, epinephrine stimulation led to a lower apparent Cl concentration after 2 min of gluconate substitution. Together these results support the concept that a particular epithelial cell type in the crypts responds to secretagogues and that the Cl permeability pathways differ between the secretory states induced by PGE2 and epinephrine. PMID- 8214064 TI - Plasticity in the gastric inhibitory innervation after immunization against VIP and vagotomy in the ferret. AB - Changes in gastric corpus tone have been characterized during two procedures that compromise the major inhibitory innervation of the stomach: immunoneutralization of endogenous vasoactive intestinal polypeptide (VIP) and chronic vagotomy. After both procedures, there was a small but significant increase in intracorpus pressure generated during ramp increases in volume compared with sham immunized controls but not when the procedures were combined in vagotomized immunized animals. Adaptation in the mechanisms controlling corpus tone was most apparent after atropine (100 micrograms/kg) and acute vagal section when tone was low in sham immunized vagotomized and vagotomized immunized animals (4.4 +/- 0.3 and 3.7 +/- 0.8 cmH2O, respectively) and high in immunized and sham immunized animals (6.5 +/- 0.4 and 6.2 +/- 0.5 cmH2O) despite a similar sensitivity to atropine. Corpus responses to low-frequency vagal stimulation were maintained in immunized animals despite the absence of a response to exogenous VIP. We conclude that gastric reservoir function adapts to the loss of the vagal inhibitory innervation by an upregulation of intrinsic reflex pathways controlling myenteric inhibitory neurons, which are non-VIPergic. PMID- 8214065 TI - Gastrin cell responses to acidification of the achlorhydric rat stomach. AB - In the rat, gastrin cells are normally exposed to the stimulatory effects of food and the inhibitory influences of acid in the gastric lumen. We have studied the effects of intragastric acid on gastrin cell function in animals in which the tonic inhibitory action of acid was removed by prior treatment with the proton pump blocker omeprazole. In fasted rats with gastric fistula treated with omeprazole, instillation of acid into the stomach produced a prompt decrease in plasma gastrin, but gastrin mRNA abundance showed a modest transient increase over a period of 2 h and thereafter no change; there was also a transient increase in tissue concentrations of the gastrin precursor progastrin that was compatible with increased gastrin synthesis. Concentrations of tissue gastrins, in general, increased after acid instillation, which can be attributed to continued synthesis in the presence of suppressed gastrin release. In rats fed ad libitum, a single dose of omeprazole (which produces achlorhydria for 24-30 h) produced an increase in plasma gastrin that peaked after 24 h and declined to control levels over the following 48 h; in contrast, gastrin mRNA abundance peaked 48 h after omeprazole before declining to control levels. The results indicate that whereas gastrin release might be promptly inhibited by intragastric acid, the changes in gastrin mRNA abundance are much slower: achlorhydria increases gastrin mRNA within 24 h, but acid takes longer to depress gastrin mRNA abundance. Over periods of a few hours, gastrin release and synthesis need not, therefore, change in parallel. PMID- 8214066 TI - Preserved organic anion transport in mutant TR- rats with a hepatobiliary secretion defect. AB - The in vivo biliary secretion of a number of organic anions in mutant TR- rats was studied. The secretion of bilirubin glucuronide (BG), the glutathione conjugate of bromosulfophthalein, dibromosulfophthalein, and indocyanine green was reduced to 2, 15, 50, and 75% of normal, respectively. Surprisingly, the secretion of bilirubin ditaurate (BDT) was entirely normal under these conditions. In isolated TR- rat liver perfusion experiments (recirculating setup), the hepatobiliary secretion of BG and BDT was reduced to 1 and 50% of normal, respectively. There was considerable residual concentrative transport of BDT under these conditions (bile-to-perfusate concentration ratio of 190 +/- 60; normal, 730 +/- 480), whereas for BG the concentration step was completely abolished (bile-to-perfusate concentration ratio of 1.3 +/- 1.0; normal, 60 +/- 40). In a single-pass isolated TR- rat liver perfusion study, BDT secretion after bolus administration (1 mumol) was abnormal; the peak secretion was retarded to 20 min after injection (normal 7.5 min), and the secretion rate was decreased to 19% of normal. BDT, as an organic dianion, is a substrate for the "canalicular multispecific organic anion transporter" (cMOAT), a carrier protein that is defective in TR- rats. Its considerable residual secretion in certain experimental conditions suggests the preservation of a low-affinity pathway for secretion of some cMOAT substrates in TR- rats. PMID- 8214067 TI - Prostaglandin modulation of the gastric vasculature and mucosal integrity in cirrhotic rats. AB - Gastric bleeding is a frequent occurrence in cirrhotic patients and may be related to altered microcirculatory responses to luminal irritants and/or vasoactive mediators. Because gastric prostaglandin synthesis has been reported to be altered in cirrhosis, we have examined the role of prostaglandins in modulating gastric perfusion velocity and mucosal integrity in cirrhotic rats. Cirrhosis was induced by bile duct ligation. Gastric perfusion velocity was measured in an ex vivo gastric chamber preparation by laser-Doppler flowmetry. The responsiveness of the mucosa to topical application of 20% ethanol was assessed. Effects of pretreatment with indomethacin or misoprostol were also determined. Gastric and hepatic prostaglandin E2 syntheses were significantly depressed (by approximately 60%) in cirrhotic vs. normal rats. Administration of indomethacin (7.5 mg/kg) to normal rats did not significantly affect gastric perfusion velocity, but in cirrhotic rats it caused a 45% reduction (P < 0.05). Topically applied misoprostol produced significantly greater (2- to 5-fold) increases in gastric perfusion velocity in cirrhotics than in controls. Cirrhotic rats were significantly more susceptible to gastric injury induced by topically applied 20% ethanol than were controls. These results suggest that gastric perfusion velocity in cirrhotic rats is modulated by endogenous prostaglandins to a much greater degree than in controls. Gastric vascular hyperresponsiveness to misoprostol may be attributable to an adaptive response to depressed endogenous prostaglandin synthesis in the cirrhotic animals. PMID- 8214068 TI - Epidermal growth factor and the maturation of intestinal sucrase in suckling rats. AB - The regulatory effect of epidermal growth factor (EGF) on the postnatal maturation of sucrase was investigated in the small intestine of suckling and weanling rats. Administration of EGF (0.5 micrograms.g body wt-1.day-1) to suckling rats caused a slight precocious induction of sucrase expression. In weanling rats EGF markedly stimulated sucrase activity; however, at both ages, the effect of hydrocortisone was more potent. When the glucocorticoid antagonist RU-38486 was administered to sucklings, the precocious induction of sucrase activity by hydrocortisone was inhibited by 80%. However, RU-38486 or adrenalectomy did not prevent the inductive effect of EGF, indicating that EGF acts in a glucocorticoid-independent manner. EGF also potentiated the effect of hydrocortisone and dietary sucrose on the precocious induction of sucrase activity in the sucklings. At weaning, administration of an antiserum specific to rat EGF significantly decreased sucrase activity. This study shows the involvement of EGF in the postnatal maturation of intestinal sucrase in the rat. PMID- 8214069 TI - Mechanism of leukotriene D4 stimulation of Cl- secretion in rat distal colon in vitro. AB - Lipoxygenase metabolites of arachidonic acid have been implicated as mediators of inflammation in inflammatory bowel disease (IBD). To assess their role in regulation of electrolyte transport, we investigated the effect of leukotriene D4 (LTD4) on ion transport across isolated rat colonic mucosa under voltage-clamp conditions. Serosal addition of LTD4 caused a dose-dependent rapid and transient increase in both short-circuit current (Isc) and potential difference, with maximal response at 1 microM. Pretreatment of the tissue with a specific LTD4 receptor antagonist (SKF-104353) inhibited these LTD4 effects. The effect of LTD4 on Isc and potential difference was also abolished by the absence of Cl- from both bathing solutions or by the presence of a Na(+)-K(+)-2Cl- cotransport inhibitor (bumetanide). A cyclooxygenase inhibitor (piroxicam) completely prevented the LTD4-induced increase in Isc. In addition, the effect of LTD4 on Isc was inhibited by either 5-hydroxytryptamine2 or 5-hydroxytryptamine3 antagonists (ketanserin and ICS-205-930, respectively). These results are consistent with a model in which LTD4 initially stimulates the synthesis from lamina propria cells of cyclooxygenase metabolites that induce electrogenic Cl- secretion, most likely via serotonergic receptors. PMID- 8214070 TI - Role of endogenous endothelin in pathogenesis of ethanol-induced gastric mucosal injury in rats. AB - The major objective of this study was to elucidate the role of endogenous endothelin (ET)-1, a potent vasoconstrictor peptide, in the pathogenesis of ethanol (EtOH)-induced gastric mucosal injury. Two series of experiments were performed in anesthetized rats. First, we examined the time course of relationships among changes in ET-1 concentrations in gastric mucosal and portal plasma, gastric mucosal hemodynamics, and mucosal damage produced by EtOH. Intragastric EtOH stimulated release of endogenous ET-1 in gastric mucosal tissue. Plasma ET-1 concentrations in the portal vein also increased after intragastric EtOH administration. ET-1 concentrations in gastric mucosal tissue and portal plasma increased significantly before gastric mucosal hemorrhagic damage occurred. Moreover, 30 min after EtOH administration there were significant correlations between gastric mucosal ET-1 concentrations and both area of gastric hemorrhagic damage as well as concentration of EtOH administered intragastrically. After intragastric EtOH administration, increase in gastric mucosal hemoglobin concentration and decrease in gastric mucosal hemoglobin oxygen saturation, estimated using reflectance spectrophotometry, occurred within 2.5 min and continued throughout the experiments. The time course of microcirculatory changes correlated closely with increases in gastric mucosal ET 1 and portal plasma ET-1 concentrations after intragastric EtOH administration. Gastric microcirculatory disturbances induced by EtOH were associated with significant decreases in gastric mucosal ATP content. Second, we examined whether pretreatment with anti-ET-1 antibody protected against EtOH-induced mucosal injury by improving mucosal microcirculation. Pretreatment with anti-ET-1 antibody microscopically and macroscopically reduced gastric mucosal hemorrhagic damage induced by EtOH and significantly reduced EtOH-induced gastric microcirculatory disturbances and decreases in gastric mucosal ATP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214071 TI - Differential expression of the neurotensin gene in the developing rat and human gastrointestinal tract. AB - Neurotensin (NT) is an important hormone regulating gut motility, secretion, and growth. The purpose of this study was to determine the developmental expression of the NT/neuromedin N gene (NT/N) in the gut and pancreas of rats and humans. We found that NT/N expression, initially low in the fetal rat jejunum and ileum, is increased by postnatal day 3. This increase is independent of contact with luminal nutrients as demonstrated by elevated NT/N expression in rat jejunoileal grafts implanted in nude mice. NT/N expression reaches maximal levels in the small bowel by postnatal day 14. After postnatal day 28, NT/N mRNA levels remain constant in the ileum but decrease in the jejunum. Transient NT/N expression is found in the colon of fetal and postnatal rats. Similar to the rat, NT/N expression is low in the human fetal ileum but increases in the adult. In the human colon, NT/N is transiently expressed in the fetus at midgestation but disappears by birth and, similarly, is not apparent in the adult. We conclude the following. 1) The NT/N gene demonstrates a complex pattern of tissue-specific expression; the jejunum and ileum show a similar pattern of expression until the end of the fourth postnatal week, when NT/N levels decrease in the jejunum to assume the distinctive adult topographical distribution with NT/N increasing along the jejunoileal axis. 2) NT/N is transiently expressed in the colon of rats and humans during a developmental stage characterized by morphological and functional similarities to the small bowel; therefore, NT/N may provide a useful endocrine marker to further define the complex differentiation pathway leading to small bowel and colonic phenotypes. PMID- 8214072 TI - Gastric ulcer induced by submucosal injection of ET-1: role of potent vasoconstriction and intraluminal acid. AB - To investigate whether submucosally applied endothelin-1 (ET-1) can induce gastric ulcer, ET-1 (62.5, 125, 250, and 500 pmol/kg) was injected in the submucosal layer of the rat gastric body. Twenty-four hours later, gastric ulcer (ulcer area: 10.31 +/- 5.13 mm2, mean +/- SE, at 500 pmol/kg, n = 8) was induced. The mucosal damage induced by the two highest doses was present even at 2 wk after their injection. Measurement of the mucosal blood flow at the injected area with three different methods (laser-Doppler flowmetry, hydrogen gas clearance, and reflectance spectrophotometry) revealed that injected ET-1 produced an extremely long-lasting vasoconstriction. Pretreatment with nicardipine, a Ca(2+) channel blocker (1 mg/kg iv), significantly attenuated the ET-1-induced mucosal damage as well as the decrease in mucosal blood flow. Pretreatment with omeprazole (5-40 mumol/kg) also, significantly attenuated the ET-1-induced mucosal damage. Combined pretreatment with omeprazole (40 mumol/kg) and nicardipine almost abolished the ET-1-induced damage. The present study shows that a novel model for experimental ulcers can be induced by submucosal injection of ET-1. PMID- 8214073 TI - Transcriptional and posttranscriptional control in synthesis of growth marker polypeptides in mouse parotids. AB - The chronic daily administration of isoproterenol provokes in mouse parotid glands the induction and progressive accumulation of a family of secretory polypeptides named polypeptides C, D, E, F, and G (polypeptides C-G). These polypeptides, which seem to be part of the family of proline-rich proteins, have been considered as molecular markers of the growth-in-size response in the mouse parotid acinar cells. In the present study, two pharmacological approaches were used to determine whether the induction and the postsecretory reappearance of polypeptides C-G may be distinguished from each other. First, actinomycin D, a transcriptional inhibitor, was found to interfere with the induction by isoproterenol but not with the postsecretory reappearance. Second, pilocarpine, a secretagogue that was found to be a very weak inducer of polypeptides C-G, was able to provoke secretion and then reappearance of the whole group of isoproterenol-induced polypeptides. Accordingly, these data suggest that the induction of polypeptides C-G is dependent on transcriptional activity and that it is unrelated to secretion stimulation. By contrast, the postsecretory reappearance of polypeptides C-G may occur even when transcriptional activity is inhibited and it would be related to the secretory activity. PMID- 8214074 TI - The human sucrase-isomaltase gene directs complex patterns of gene expression in transgenic mice. AB - Sucrase-isomaltase (SI) is an enterocyte-specific gene that is expressed in complex developmental and spatial patterns. In this study, we examine the ability of regulatory elements within the human SI (hSI) gene to direct appropriate cell lineage and spatial patterns of expression in transgenic mice. Transgenic mouse lines were established using a construct containing bases -3424 to +54 of the hSI gene linked to the human growth hormone (hGH) structural gene. In each transgenic line, hGH mRNA and protein were expressed only in the small intestine and colon. In contrast to the endogenous mouse SI (mSI) gene, which was expressed along the entire length of the small intestine, hGH mRNA expression was predominantly found in the distal jejunum and ileum, with very low levels in more proximal portions of the small intestine. However, the pattern of transgene expression along the small intestinal crypt-villus axis was identical to the pattern of the endogenous mSI gene. These results suggest that regulatory elements necessary for intestine specific transcription and differential expression along the intestinal crypt villus axis are included in the 5'-flanking region of the hSI gene. Furthermore, these data suggest that different DNA regulatory regions regulate transcription along the horizontal intestinal axis. In the colon, there was aberrant expression of hGH in a subpopulation of enteroendocrine cells that contained peptide tyrosine tyrosine (PYY). This suggests that there are DNA regulatory elements, missing in the transgene construct, which normally suppress expression of the endogenous mSI gene in these cells. Taken together, these findings define the SI gene as a useful model for studies of differentiation, cell lineage determination, and mechanisms of complex spatial gene expression in the intestine. PMID- 8214075 TI - Duodenal acid-induced inhibition of gastric motility and emptying in rats. AB - The mechanism by which acid in the duodenum inhibits proximal gastric motor function and delays emptying was investigated in urethan-anesthetized and awake rats. Gastric motility inhibited by duodenal acid (0.2 N HCl) in urethan anesthetized rats was attenuated by 68 and 54%, respectively, by functional ablation of the vagal or spinal sensory innervation with capsaicin. 5 Hydroxytryptamine3 receptor blockade with zacopride (0.2 mg/kg ip) or cholecystokinin (CCK)-A-type receptor blockade with MK-329 (1 mg/kg ip) had no effect on the motility response to acid. In awake rats with chronically implanted gastric and duodenal cannulas, perfusion of the duodenum with acid (0.1 and 0.2 N HCl) inhibited gastric emptying of a nonnutrient liquid (38 and 59%, respectively). Blockade of CCK-A-type receptors reduced by 30% inhibition of gastric emptying induced by 0.1 N HCl. However, functional ablation of the vagal or spinal sensory innervation, 5-hydroxytryptamine3 receptor blockade, or immunoneutralization of secretin by systemic administration of a polyclonal antibody (no. 7842, 1 ml ip) had no effect on acid-induced (0.1 N HCl) inhibition of gastric emptying. Perfusion of the duodenum with 0.2 N HCl but not 0.1 N HCl inhibited proximal gastric motility in awake rats. These results suggest that 1) a duodenal acid load inhibits gastric emptying in part by a mechanism involving CCK and 2) decreased proximal gastric motility plays a minor role in inhibition of gastric emptying in response to acid. PMID- 8214076 TI - Calibration of albumin-fatty acid binding constants measured by heptane-water partition. AB - Most measurements of binding affinity of albumin for long-chain fatty acids are based on heptane-water partition. In this method, equilibrium partition of fatty acid between heptane and an albumin-containing buffer is calibrated using the partition ratio between heptane and buffer in the absence of protein. In the current study, we used a variety of techniques to examine potential problems with this approach. Hydrophobic impurities in commercial [3H]palmitate preparations were incompletely removed by standard purification techniques. These impurities contributed from 5% of the total radioactivity in the heptane phase at low albumin concentrations (5 microM) to 62% at higher albumin concentrations (500 microM), thus confounding determination of binding affinity. These were identified by gas chromatography/mass spectroscopy as radio-labeled glycerol monopalmitate and monostearate. When albumin was not present, the partition ratio was similar to values reported by others. However, our results varied by a factor of four (265-1,119) depending on how the solutions were prepared. Although a true equilibrium partition must not depend on starting conditions, the partition ratio after 24-72 h was > 2x as large when tracer [3H]palmitate was added to the heptane phase than when it was added to the aqueous phase. Results also depended on the relative volumes of heptane and buffer used, approaching a maximum of 1,445 +/- 112 for very low heptane/buffer volume ratios. Much of this variability was due to hydrophilic impurities in [3H]palmitate, which ranged from 0.2 to 1.2% in commercial lots down to 0.1-0.5% after alkaline ethanol extraction and < 0.05% after thin-layer chromatography (TLC).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214077 TI - Propionate activates multiple ion transport mechanisms in the HT29-18-C1 human colon cell line. AB - Short-chain fatty acids (SCFAs) are the major solutes and the major anions in the colonic lumen. We studied the response of suspended HT29-18-C1 cells (an epithelial cell line derived from a human colon carcinoma) to SCFA exposure. Cellular response was evaluated by measurement of cell volume (Coulter counter), intracellular pH [pHi; measured fluorometrically with 2',7'-bis(2-carboxyethyl)-5 (6)-carboxyfluorescein (BCECF)], and intracellular Na+, K+, and Cl- content (flame photometry and chloride titrator). Exposure to 130 mM propionate in isosmotic medium causes a rapid decrease in pHi and activates pHi recovery via amiloride-sensitive Na-H exchange. In the presence of propionate, Na-H exchange also causes cell swelling to a peak volume 11% above control cells and causes a 2.8-fold increase in intracellular Na+ content. After peak swelling, a regulatory volume decrease (RVD) significantly reduced volume and intracellular Na+ returned to baseline. Other SCFAs (acetate, butyrate, and valerate) also elicit swelling and RVD. Activation of the Na(+)-K(+)-adenosinetriphosphatase (ATPase) is required to return Na+ to normal levels and to indirectly provide ion gradients required for propionate-induced RVD, but Na(+)-K(+)-ATPase activity does not directly mediate RVD. When 1 mM 4-acetamido-4'-isothiocyanostilbene-2,2' disulfonic acid (SITS) is added in the presence of propionate, RVD was inhibited and cell Na+ content increased. Cl- depletion inhibited propionate-induced RVD and diminished the effect of SITS. PMID- 8214078 TI - Cerebral metabolic and histological effects of thioacetamide-induced liver failure. AB - Acute liver failure was induced in rats by successive administrations of thioacetamide over 3 days. At progressing stages of hepatic encephalopathy (HE), brains were fixed with microwave irradiation for analysis of metabolite levels or with formaldehyde for histopathological analysis. Metabolite levels were determined using 1H-nuclear magnetic resonance spectroscopy of perchloric acid extracts of the frontal cortex, parietal or occipital cortex, hippocampus, striatum, brain stem, and cerebellum. After thioacetamide treatment, thioacetamide and its metabolites were detected in the brains at levels that did not correlate with the stage of HE. No changes were observed in the levels of N acetylaspartate, alanine, gamma-aminobutyric acid, aspartate, or inositol in any brain region after thioacetamide treatment. HE was accompanied by elevated glutamine, glucose, and lactate throughout the brain. At all stages of HE, taurine was decreased in the neocortex and hippocampus, and glutamate and choline compounds were decreased in the frontal cortex. None of the metabolite changes showed progression with the stage of HE. Progressing HE was accompanied by increasing neuronal injury in layer III of the neocortex, in the Purkinje cells of the cerebellum, and in the hippocampus, particularly in the CA4 sector. The similarity of this distribution of injury to that associated with excitotoxic injury suggests that metabolic abnormalities after acute hepatic failure may give rise to adverse effects at excitatory (glutamatergic) neuronal receptors, leading to neuronal injury and clinical symptoms of progressing encephalopathy in this model. However, neuronal injury and the presence of thioacetamide and its metabolites in the brain raise questions about the validity of thioacetamide induced liver failure as a model for clinical HE. PMID- 8214079 TI - Evaluation and validation of microsphere technique for determination of pancreatic blood flow. AB - The purpose of this study was to evaluate the radiolabeled microsphere technique for pancreatic blood flow measurements. Using a canine model with an isolated pancreatic circulation, we assessed the shunting of 11- and 15-microns-diam microspheres in the pancreas, correlated pancreatic blood flow measurements obtained with the microsphere technique with those made with an ultrasonic flow probe, and determined the effects of high doses of microspheres on pancreatic blood flow and its measurement. Microspheres of 11 microns demonstrate significant shunting through the pancreatic microcirculation with underestimation of pancreatic blood flow of approximately 10% compared with results obtained with 15-microns microspheres. There is a close linear relationship between flow results obtained with 15-microns microspheres and with an ultrasonic flow probe for both the resting (r = 0.85) and the secretin-stimulated pancreas (r = 0.97). Left atrial injections of very large doses of 15-microns microspheres (50 x 10(6)) caused an acute transient reduction of pancreatic blood flow (to 39% of baseline flow) with a return to baseline values within 2 min. The accuracy of flow results and absence of physiological changes after repeated injections support the use of 15-microns microspheres for pancreatic blood flow measurements. PMID- 8214080 TI - Limitations of laser-Doppler velocimetry and reflectance spectrophotometry in estimating gastric mucosal blood flow. PMID- 8214081 TI - A protein structural approach to the solution of biological problems: alpha 1 antitrypsin as a recent example. AB - alpha 1-Antitrypsin is a circulating serine proteinase inhibitor that protects the lungs against proteolysis by the enzyme neutrophil elastase. Most northern Europeans have only the normal M form, but some 4% are heterozygotes for the Z deficiency mutant. This mutant is characterized by the substitution of a positively charged lysine residue for a negatively charged glutamic acid at position 342 and results in normal gene translation but reduced protein secretion into the plasma. The plasma levels of antitrypsin in homozygotes are only 15% of normal, the other 85% being retained in the endoplasmic reticulum of the hepatocyte. This review describes the effect of the Z mutation on the structure and function of antitrypsin and illustrates the importance of understanding protein structure in solving the mechanism of Z antitrypsin retention within the liver. We demonstrate that antitrypsin accumulation in the liver results from a unique interaction between antitrypsin molecules. The Z mutation perturbs the gap between the third and fifth strands of the A sheet, allowing the reactive center loop of one molecule to insert into the A sheet of a second. This loop-sheet polymerization results in the formation of chains of protein which form insoluble inclusions in the endoplasmic reticulum, resulting in hepatocellular damage and cirrhosis. In addition, the Z mutation results in a distortion of the circular dichroic spectrum, a rearrangement of the reactive center loop with respect to the A sheet, and a reduction in association rate constant with the cognate proteinase neutrophil elastase. PMID- 8214082 TI - Sulfhydryl-depleting agents, but not deferoxamine, modulate EDRF action in cultured pulmonary arterial cells. AB - The potential role of intracellular sulfhydryls and iron on the biological activity of endothelium-derived relaxing factor (EDRF) released basally from bovine pulmonary arterial endothelial (BPAE) cells was investigated in a cultured cell bioassay system, by measuring N omega-nitro-L-arginine-sensitive guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in rabbit pulmonary arterial smooth muscle (SM) cells. The role of sulfhydryls in the biosynthesis of EDRF was studied by selectively exposing the endothelial cells to thiol-depleting agents. Both N-ethylmaleimide (NEM) and maleic acid diethyl ester (DEM) inhibited EDRF induced cGMP accumulation in a dose-dependent manner. To study the requirement of SM thiols in the metabolism of EDRF to a stimulator of cGMP formation, SM were selectively exposed to NEM and DEM before bioassay with control, untreated BPAE. DEM and NEM inhibited cGMP formation in response to EDRF by 30 and 68%, respectively. The requirement of SM sulfhydryls was further investigated in the stimulation of SM cGMP accumulation elicited by nitrosothiols [S-nitroso-L cysteine, S-nitroso-mercaptoproprionic acid, and sodium nitroprusside (SNP)]. NEM pretreatment of SM cells abolished cGMP responses to all vasodilators; DEM did not affect the nitrosothiol responses but reduced by 30% the cGMP accumulation to SNP. The role of iron in the endothelial synthesis of EDRF was assessed by chelating endothelial low-molecular-weight iron compounds. Exposure of BPAE to deferoxamine mesylate had no effect on cGMP accumulation in SM, suggesting that deferoxamine-available iron is not necessary for the endothelial stimulation of SM cGMP formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214083 TI - Prostaglandin secretion by guinea pig tracheal epithelial cells caused by eosinophil major basic protein. AB - We examined the effect of eosinophil major basic protein (MBP) on prostaglandin (PG) secretion from guinea pig tracheal epithelial (GPTE) cells. Primary cultures of GPTE cells were incubated with 10(-6) M MBP for up to 6 h and then stimulated with 10(-6) M bradykinin (BK). PGE2, 6-ketoprostaglandin F1 alpha (PGF1 alpha), PGF2 alpha, and thromboxane B2 (TxB2) concentrations in media were determined by enzyme-linked immunoabsorbent assay (EIA). Incubation with MBP for 6 h caused secretion of both PGE2 (17,614 +/- 4,416 vs. 1,426 +/- 555 pg/10(6) cells at baseline, P < 0.001, n = 7) and PGF2 alpha (20,303 +/- 5,724 vs. 3,790 +/- 1.075 pg/10(6) cells at baseline, P < 0.002, n = 7). Secretion of PGE2 and PGF2 alpha stimulated by MBP required at least 2 h. Incubation with MBP for 6 h also augmented the subsequent response to BK: PGE2 secretion was 29,215 +/- 6,853 vs. 3,445 +/- 1,041 pg/10(6) cells for BK alone (P < 0.0001), and PGF2 alpha secretion was 25,407 +/- 6,237 vs. 5,213 +/- 1,535 pg/10(6) cells for BK alone (P < 0.0001). MBP did not change 6-keto-PGF1 alpha and TxB2 secretion. Incubation of GPTE cells from seven animals with polylysine, a protein with mass and ion charge similar to MBP, for 2 h, both caused secretion of PGE2 (8,579 +/- 3,244 vs. 788 +/- 419 pg/10(6) cells at baseline, P < 0.01) and augmented the response to BK (12,732 +/- 4,788 vs. 1,653 +/- 680 pg/10(6) cells after BK alone, P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214084 TI - Neutrophil-mediated endothelial angiotensin-converting enzyme dysfunction: role of oxygen-derived free radicals. AB - We examined the mechanisms whereby phorbol 12-myristate 13-acetate (PMA) activated rabbit peritoneal neutrophils [polymorphonuclear leukocytes (PMN)] altered endothelial-bound angiotensin-converting enzyme (ACE) activity in cultured bovine pulmonary arterial endothelial cells (EC). PMA or PMN alone had no effect on ACE activity. When PMN were coincubated with PMA (10 ng/ml) for 4 h in Earle's salt solution, endothelial ACE activity was decreased by 87%. No EC cytotoxicity was observed at this time as determined by 51Cr release from prelabeled EC. Activated PMN-mediated decreased ACE activity was inhibited by catalase (2,000 U/ml) but not by superoxide dismutase (300 U/ml). The decrease in ACE activity was also inhibited by the hydroxyl radical scavenger dimethylthiourea (5 mM) but not mannitol (5 mM), which does not cross cell membranes. Pretreatment of EC with the iron chelator deferoxamine mesylate (1-10 mM) for 4 h attenuated the PMN-mediated decrease in ACE activity, as did the thiol reducing agent, 2-mercaptoethanol (0.1 mM), and the myeloperoxidase inhibitor, cyanide (5 mM), but not azide (1-50 mM). Treatment with the proteinase inhibitor phenylmethylsulfonyl fluoride, with human alpha-antitrypsin, or with the nitric oxide synthase inhibitor N omega-nitro-L-arginine had no effect on PMN mediated ACE dysfunction. These results suggest that PMN-mediated ACE dysfunction may be due to the production of hydrogen peroxide by PMN and its subsequent conversion into hydroxyl radicals. PMID- 8214085 TI - Effect of tunicamycin on maturation of fetal mouse lung. AB - The mesodermal capsule of the fetal lung plays a role in differentiation of the respiratory region. It has been proposed for other epithelial organs that the mesodermal capsule influences development by modifying the basal lamina or the extended extracellular matrix. The effect could be on deposition or turnover of collagens, proteoglycans, and/or glycoproteins. This study tests the role of glycoproteins in differentiation of respiratory endings by inhibiting their synthesis with the antibiotic tunicamycin (TM). Lungs at 16 and 18 days gestation and 3 days after birth were cultured with TM and examined for morphological and biochemical differences from normal controls. With TM, alveolar regions did not expand properly and formed fewer type I pneumocytes, although type II pneumocytes were unaffected. The epithelium of untreated respiratory regions showed greater incorporation of radioactive mannose than the airways region or mesenchyme. This incorporation was diminished in TM, but the pattern persisted. Comparison with the results obtained with beta-xyloside suggested that differentiation of type I and type II pneumocytes is under separate control. PMID- 8214086 TI - Mucinlike glycoproteins from cat tracheal gland cells in primary culture. AB - In a recent study (D. J. Culp, D. K. P. Lee, D. P. Penney, and M. G. Marin. Am. J. Physiol. 263: L264-275, 1992), we reported that primary cultures of cat tracheal gland cells expressed histological, ultrastructural, and immunological characteristics of mucous cells when cultured on floating gels of rat tail collagen (released-gel cultures) compared with cells cultured on glutaraldehyde fixed collagen gels (fixed-gel cultures). We therefore collected culture medium from gland cells grown under both culture conditions for determination and comparison of glycoconjugates with characteristics of mucin glycoproteins. Cells were cultured in the presence of [3H]glucosamine, and material of high molecular weight and density (HMD material) was isolated. HMD material from both culture conditions were each resistant to heparitinase and heparinase, whereas 72 and 25% of the radiolabel in released-gel and fixed-gel HMD material, respectively, was resistant to chondroitinase ABC. Material resistant to chondroitinase ABC was analyzed further. Both samples contained a single broad glycoprotein band [relative molecular weight (M(r)) > 250,000] after sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and had amino acid profiles similar to airway mucin. The sample from fixed-gel cultures had nearly equal amounts of carbohydrate and protein, was highly enriched in N-acetylglucosamine, contained mannose, displayed little blood group A immunoreactivity, and had few O-linked oligosaccharides. Conversely, the sample from released-gel cultures contained 80% carbohydrate, was composed of monosaccharides characteristic of airway mucins, displayed blood group A immunoreactivity, and contained oligosaccharides O-linked via N-acetylgalactosamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214087 TI - Matrix Gla protein mRNA expression in cultured type II pneumocytes. AB - Matrix Gla protein (MGP) was first isolated from the matrix fraction of bone. This highly conserved vitamin K-dependent protein of 14 kDa has been identified in numerous tissues and cells, and its mRNA was recently found to be abundant in rat lung. Relatively low MGP protein levels in many soft tissues where its mRNA is high suggests an important secretory function for this protein. We have found a high specific activity of vitamin K-dependent carboxylase in microsomes of rat pulmonary type II cells and the presence of numerous endogenous substrates, including one of 13-15 kDa. To investigate the possibility that MGP and its mRNA could be localized in type II cells, rat MGP and actin cDNA probes were hybridized to total RNA obtained from freshly isolated type II cells and from cells cultured for up to 6 days. MGP mRNA increased 5- to 6-fold relative to beta actin mRNA from days 3 to 6 in primary culture and MGP secretion increased nearly 60-fold during that interval. MGP mRNA and MGP secretion decreased 25-75% if cultures were supplemented with vitamin K quinone. Vitamin K deficiency, caused by carbon stripping the serum or treatment of cell cultures with warfarin, resulted in an induction of carboxylase activity and elevated MGP mRNA. In parallel experiments, carboxylase specific activity also increased during culture in the presence or absence of vitamin K. Retinoic acid further increased steady state mRNA levels and MGP secretion at later culture intervals, an effect which was serum dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214088 TI - PO2-dependent hydroxyl radical production during ischemia-reperfusion lung injury. AB - Pulmonary ischemia-reperfusion results in transient hypertension and edema formation. Implicated in this injury are partially reduced oxygen species including the highly reactive hydroxyl radical. We measured ischemia-reperfusion injury and hydroxyl radical production following 90 min of either air-ventilated, N2-ventilated, or nonventilated ischemia in an isolated rabbit lung preparation. We found that edema formation was independent of alveolar oxygen tension (PO2); all ischemic groups had similar edema formation, regardless of the type of ventilation. Weight gain was 37-50 g of fluid during 40 min of reperfusion. Production of hydroxyl radical, measured by nonenzymatic hydroxylation of salicylate, was influenced by PO2 with a significant increase after air ventilated ischemia (P < 0.05) but not after N2-ventilated ischemia. Treatment with dimethylthiourea or superoxide dismutase reduced edema formation 60-80% after air (P < 0.05)- and N2 (P < 0.05)-ventilated ischemia, whereas treatment with catalase protected only N2-ventilated ischemia (P < 0.05). Our results implicate two distinct mechanisms by which partially reduced oxygen species may contribute to pulmonary ischemia-reperfusion injury. One is by a mechanism capable of generating hydroxyl radical at normal PO2; the second is from reactions active at low PO2, the products of which are metabolized readily by extracellular enzymatic scavengers. The precise mechanisms of oxidant generation are not clear, but the findings suggest that a complex oxidative injury occurs during ischemia-reperfusion. PMID- 8214089 TI - Hyperoxic exposure of developing rat lung decreases tropoelastin mRNA levels that rebound postexposure. AB - These studies were undertaken to determine whether tropoelastin message expression in lung parenchymal tissue is altered in rats reared in an hyperoxic environment during the period of time that alveolar septation normally occurs. Rat pups were exposed to > 95% oxygen from days 4 to 14 and killed during the exposure and recovery periods. Results of in situ hybridizations indicated a delay in peak tropoelastin (TE) message levels in oxygen-exposed rats vs. controls, day 16 vs. day 11, respectively. In addition, lung parenchymal TE mRNA levels in the oxygen-exposed pups remained elevated through day 23, 1 wk after TE mRNA levels had decreased in controls. These observations suggest that the regulatory control of elastin synthesis during lung alveolar septation is altered by hyperoxic exposure. In a separate experiment, rat pups were exposed to > 95% oxygen during the period of alveolarization and followed for 4 wk postexposure. Pulmonary function measurements were conducted to determine whether lung function was altered postexposure and, if so, whether recovery occurred. We also used stereological techniques to quantitate the total length of lung parenchymal elastic fibers to determine whether elastic fiber content in the oxygen-exposed pups was restored to normal levels during the month postexposure. Although the total length of elastic fibers in lung parenchyma was found to be greater in oxygen-exposed than control pups from postnatal days 22 to 41, pressure-volume curves indicated that lungs of the oxygen-exposed pups tended to be more compliant than controls, suggesting that abnormal elastic fiber assembly might have been a contributing factor. PMID- 8214090 TI - Effects of activated eosinophils cultured from human umbilical cord blood on guinea pig trachealis. AB - We studied the biochemical indexes and corresponding induction of airway smooth muscle contraction and hyperresponsiveness in guinea pig trachealis in situ caused by cultured eosinophils derived from mononuclear cell fractions of human umbilical cord blood. A method was developed that permitted isolation of large numbers of cells (approximately 2.6 x 10(6)/ml cord blood) having morphological and immunohistological characteristics of human peripheral blood eosinophils. After activation with 10(-6) M formyl-Met-Leu-Phe + 5 micrograms/ml cytochalasin B (fMLP + B), in situ application to the epithelial surface of 6 x 10(6) cord derived eosinophils (CDE)/surface area (cm2) caused 1.46 +/- 0.24 g/cm maximal active tracheal tension in guinea pig tracheal smooth muscle (P < 0.005 vs. zero baseline). Muscarinic responsiveness also was augmented in situ in trachealis preparations treated with activated 3-wk CDE. Contraction caused by 3 x 10(-7) mol/kg iv methacholine (MCh) was 0.94 +/- 0.18 g/cm at baseline vs. 1.80 +/- 0.24 g/cm after activated CDE (P = 0.02). Control (sham-activated) 3-wk CDE caused neither significant contraction [0.41 +/- 0.16 g/cm active tension (AT); P < 0.05 vs. fMLP+B] nor augmented muscarinic responsiveness. Cells cultured for 5 wk contained fewer granules than 3-wk CDE and also caused less direct contraction of trachealis (0.73 +/- 0.14 g/cm AT) after activation (P < 0.01 vs. 3-wk CDE). Both contraction and muscarinic augmentation were blocked in 3-wk CDE after blockade of leukotriene C4 (LTC4) synthesis by pretreatment with the 5-lipoxygenase inhibitor, A63162 (50 microM). Treatment with A63162 had no effect on the stimulated release of eosinophil peroxidase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214091 TI - Heat stress protein-associated cytoprotection of inner medullary collecting duct cells from rat kidney. AB - Although heat stress proteins (HSPs) mediate thermotolerance, the cellular targets of thermal injury and mechanisms of acquired cytoprotection are unknown. To describe the metabolic effects of hyperthermia and the potential mechanisms of thermotolerance, the following were measured in inner medullary collecting duct cells after a 43 degrees C and/or a 50 degrees C thermal insult: 1) state III mitochondrial respiration (SIII MR), 2) glycolytic rate, 3) lactate dehydrogenase activity, 4) membrane permeability, and 5) HSP 72 content. Compared with controls incubated at 37 degrees C, cells heated to 50 degrees C showed a 30 and 50% reduction in glycolysis and SIII MR, respectively. After heating to 50 degrees C, the cell membrane remained intact and immunoreactive HSP 72 was not detected. In contrast, heating to 43 degrees C induced accumulation of HSP 72 and transiently increased both SIII MR and glycolysis. In addition, prior exposure to 43 degrees C completely prevented the fall in SIII MR and glycolysis anticipated with a subsequent 50 degrees C insult. Cytoprotection gradually diminished over several days and correlated with the disappearance of HSP 72. Preservation of oxidative and anaerobic metabolism associated with HSPs may be important in developing resistance to thermal injury. PMID- 8214092 TI - Renal mouse proximal tubular cells are more susceptible than MDCK cells to chemical anoxia. AB - To elucidate the mechanisms responsible for the resistance of continuous cell lines to anoxic injury, we have compared the effects of ATP depletion induced by chemical anoxia on primary cultures of mouse proximal tubular (MPT) cells and on Madin-Darby canine kidney (MDCK) cells. Inhibition of ATP production by cyanide and 2-deoxyglucose (CN+DOG) in the absence of dextrose reduced cell ATP content to < 5% of control values in MPT cells and caused progressive deterioration in mitochondrial function as well as loss of cell viability in these cells. Cell free fatty acid (FFA) content rose from 4.3 +/- 0.9 to 23.7 +/- 2.0 micrograms/mg of total lipid weight after 4 h of CN + DOG (P < 0.05). The mitochondrial injury and cell death induced by CN + DOG in MPT cells was ameliorated by the addition of fatty acid-free bovine albumin to the cell medium, which reduced cell FFA content during chemical anoxia from 25.0 +/- 3.0 to 10.4 +/- 2.0 micrograms/mg (P < 0.05). The phospholipase A2 (PLA2) inhibitor, mepacrine, also resulted in functional protection and reduction of cell FFA content from 20.2 +/- 2.3 to 15.9 +/- 1.7 micrograms/mg (P < 0.05). These data suggest a role for phospholipase activation and accumulation of toxic lipid metabolites in the pathophysiology of MPT cell injury. We then compared cell injury induced by CN + DOG in MPT and MDCK cells. Despite comparable reduction in cell ATP content in the two cell types, injury was far more severe in MPT than MDCK cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214093 TI - PDGF-induced Egr-1 expression in rat mesangial cells is mediated through upstream serum response elements. AB - Platelet-derived growth factor (PDGF) has been implicated in the process of mesangial cell (MC) proliferation in vitro and in vivo. To investigate early changes in gene expression that couple biochemical events with changes in phenotype in PDGF-stimulated cultured MC, we studied expression of the early growth response gene 1 (Egr-1), a member of the family of immediate early genes. Our findings show that protein tyrosine phosphorylation is required for induction of Egr-1 mRNA and proliferation by PDGF in MC. Nuclear run-off assays show that Egr-1 induction occurs at the transcriptional level. An 11.3-fold increase in Egr 1 transcription rate was observed as early as 5 min after PDGF stimulation of MC. Promoter deletion analysis revealed that the region critical for Egr-1 inducibility by PDGF contains serum response element (SRE) consensus sequences. Sequential deletion of the Egr-1 SREs led to a stepwise drop in promoter activity, suggesting that PDGF induces Egr-1 transcription through SREs in the Egr-1 promoter region. Interestingly, electrophoretic mobility shift assays, with an Egr-1 SRE as probe, demonstrate that protein-SRE complexes of differing size undergo modest quantitative changes following PDGF stimulation. These data in MC suggest that the upstream SREs mediate the transcriptional induction of Egr-1 by PDGF. PMID- 8214094 TI - Insulin stimulates Na+, Cl-, Ca2+, and Mg2+ transports in TAL of mouse nephron: cross-potentiation with AVP. AB - Insulin (Ins) decreases Na+ delivery in the final urine. To determine whether the loop of Henle participates in this reduction, the effects of Ins were tested on cortical (CTAL) and medullary thick ascending limbs (MTAL) of the mouse nephron, microperfused in vitro. In the MTAL, Ins increased the transepithelial potential difference (Vt) and the Na+ and Cl- net reabsorption fluxes (JNa and JCl, respectively) in a dose-dependent manner, the threshold being below 10(-9) M. At 10(-7) M, Ins reversibly increased JNa and JCl, leaving Mg2+ and Ca2+ fluxes (JMg and JCa, respectively) close to zero. In the CTAL, 10(-7) M Ins reversibly increased Vt, JNa, JCl, JMg, and JCa. In CTAL segments perfused under asymmetrical conditions, with a bath-to-lumen-directed NaCl gradient (lumen 50 mM NaCl, bath 150 mM NaCl), addition of 10(-7) M Ins to the bath resulted in a large increase in JMg and JCa. Thus the responses of CTAL and MTAL to Ins are in all ways similar to those already reported for the adenosine 3',5'-cyclic monophosphate (cAMP)-generating hormones acting on these nephron segments. When 10(-10) M arginine vasopressin (AVP) and 10(-7) M Ins were used in combination, previous addition of one hormone to the bath potentiated the response to the second hormone. In cAMP accumulation experiments, performed in the presence of a phosphodiesterase inhibitor, the amounts of cAMP formed with 10(-7) M Ins and 10( 10) M AVP (which elicit maximal physiological responses in these segments) were in the same range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214095 TI - Thyroid hormone stimulates Na(+)-K(+)-ATPase gene expression in cultured rat mesangial cells. AB - Thyroid hormone 3,3',5-triiodothyronine (T3) is an important regulator of Na(+) K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity in a variety of mammalian target tissues. In the present study, we examined the expression of Na(+)-K(+)-ATPase alpha- and beta-subunit mRNAs by T3 in cultured rat mesangial cells. Northern blot analysis of total RNA isolated from cultured rat mesangial cells revealed the expression of mRNAs encoding Na(+)-K(+)-ATPase alpha 1- and beta 1-subunits; mRNAs encoding alpha 2- and alpha 3-subunits were undetectable. Exposure of mesangial cells to T3 (10(-8) M) caused a threefold increase in the alpha 1-mRNA expression, which was first detected at 6 h and sustained for at least 48 h. The beta 1-mRNA expression was gradually increased by T3, with a maximum fourfold elevation at 48 h. The 50% effective concentration (EC50) for the alpha 1- and beta 1-mRNA induction by T3 was approximately 10(-10) M. The half-life of alpha 1-mRNA analyzed by actinomycin D chase was approximately 3 h and was not affected by T3. The augmented alpha 1-mRNA expression by T3 was associated with a 2.4-fold increase in the alpha 1-subunit protein accumulation and a 1.6-fold increase in Na(+)-K(+)-ATPase activity. These data suggest that thyroid hormone stimulates Na(+)-K(+)-ATPase gene expression, protein accumulation, and enzyme activity in rat mesangial cells. PMID- 8214096 TI - Oxidant-induced alterations in glucose and phosphate transport in LLC-PK1 cells: mechanisms of injury. AB - To determine the effects of oxidant injury on specialized functions of proximal tubular epithelial cells, we determined sodium-dependent uptake of glucose ([alpha-14C]methylglucoside) and phosphate (32Pi) in LLC-PK1 cells after exposure to 0-500 microM hydrogen peroxide. Oxidant stress resulted in significant (P < 0.01) inhibition of glucose and phosphate transport. Decreased transport of glucose and phosphate was associated with marked ATP depletion, decreased activity of the sodium pump as determined by 86Rb uptake, direct inhibition of Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity, and an increase in intracellular sodium content, whereas intracellular potassium content declined. Decreased glucose and phosphate transport, inhibition of 86Rb uptake and Na(+)-K(+)-ATPase activity, and altered intracellular ion content were prevented by catalase and partially prevented by the membrane-permeable iron chelator phenathroline, whereas the slowly membrane-permeable iron chelator deferoxamine had little or no effect. To determine whether oxidant injury could also inhibit transporter function at the membrane level, plasma membrane vesicles were isolated from LLC-PK1 cells exposed to 500 microM hydrogen peroxide. Such membrane vesicles exhibited decreased sodium-dependent glucose transport, whereas sodium-dependent phosphate transport was not altered. We conclude that oxidant injury results in ATP depletion and inactivation of Na(+)-K(+)-ATPase which leads to disruption of the normal ion gradients sufficient to interfere with glucose and phosphate transport. Glucose transport is also inhibited by disruption of transporter activity within the plasma membrane. These alterations are mediated in part by the intracellular generation of an iron-dependent radical. PMID- 8214097 TI - The urease inhibitor acetohydroxamic acid is transported by the urea pathway in rat terminal IMCD. AB - Acetohydroxamic acid (AHA), a urea analogue, is used clinically to dissolve struvite stones because it inhibits the urease produced by Proteus mirabilis. To be effective, the concentration of AHA must be high in the collecting duct system and final urine. Because AHA is structurally similar to urea, we investigated whether AHA is transported by the urea carrier found in the terminal inner medullary collecting duct (IMCD) and the erythrocyte. We examined AHA transport under four conditions known to affect urea movement across the terminal IMCD, i.e., stimulation by vasopressin (AVP) and hyperosmolality, and inhibition by phloretin and urea analogues. The AHA permeability was determined with a 10 mM bath-to-lumen AHA gradient. AHA was measured by ultramicrocolorimetry. Addition of 1 nM AVP to the bath increased the AHA permeability of the perfused terminal IMCD. Increasing perfusate and bath osmolality from 290 to 690 mosmol/kgH2O (by adding NaCl) also increased tubule permeability to AHA. Addition of either 0.25 mM phloretin to the bath or 200 mM thiourea to the lumen reversibly inhibited the AVP-stimulated AHA permeability. AHA-induced osmotic lysis of erythrocytes was inhibited by phloretin or thionicotinamide; AHA inhibited the osmotic lysis induced by the urea analogue acetamide. Thus, in the rat terminal IMCD, both urea and AHA transport are stimulated by AVP and hyperosmolality, and both are inhibited by phloretin and thiourea. In erythrocytes, both urea and AHA transport are inhibited by phloretin or thionicotinamide. Thus AHA is transported by the urea carrier in the terminal IMCD and erythrocyte.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214098 TI - Continuous telemetric blood pressure monitoring and glomerular injury in the rat remnant kidney model. AB - The pathogenesis of glomerular injury in the remnant kidney (RK) model remains controversial. Increased glomerular transmission of systemic hypertension has been postulated to be an important pathogenic mechanism, but the precise relationship between systemic pressures and glomerular injury has not been defined because of the limitations of the tail-cuff method. Systolic blood pressure (BP) was continuously recorded radiotelemetrically at 10-min intervals for 6 wk in rats after approximately 5/6 renal ablation (n = 16) or sham ablation (n = 7). Overall mean systolic BP in RK rats was significantly higher than sham (138 +/- 3.3 vs. 117 +/- 1.3 mmHg, P < 0.01). Additionally, marked lability of systolic BP was observed in RK rats as compared with sham rats. Glomerular injury was essentially confined to RK rats, but the percentage of injured glomeruli ranged between 1 and 55%. Glomerular injury in individual animals was strongly correlated (r = 0.88) with the mean systolic BP during the last approximately 4 wk and with the frequency of systolic BP readings of > 140 mmHg. These data strongly suggest that transmission of systemic hypertension to the renal microvasculature plays a predominant role in the pathogenesis of glomerular injury in the RK model and also support the potential usefulness of the radiotelemetric technique to investigate hypertensive target organ injury. PMID- 8214099 TI - Different mechanisms of renal Na-K-ATPase regulation by protein kinases in proximal and distal nephron. AB - We recently reported a novel intracellular mechanism of Na-K adenosinetriphosphatase (Na-K-ATPase) regulation in the cortical collecting duct (CCD) by agents that increase cell adenosine 3',5'-cyclic monophosphate (cAMP), which involves stimulation of protein kinase A (PKA) and phospholipase A2 (PLA2). We now determined whether this mechanism also operates in other nephron segments. In the medullary thick ascending limb (MTAL) dopamine, the DA1 agonist fenoldopam, forskolin, or dibutyryl-cAMP inhibited Na-K-ATPase activity, similar to results in CCD. In both segments this effect was blocked by 20-residue inhibitory peptide (IP20), a peptide inhibitor of PKA, but not by staurosporine, a protein kinase C (PKC) inhibitor. PKC activators phorbol 12-myristate 13 acetate, phorbol 12,13-dibutyrate, and 1,2-myristate 13-acetate, phorbol 12,13 dibutyrate, and 1,2-dioctanoylglycerol had no effect on Na-K pump activity in either CCD or MTAL. In contrast, all three PKC activators inhibited pump activity in the proximal convoluted tubule (PCT), an effect reproduced only by dopamine or by parathyroid hormone [PTH-(1-34)]. In PCT the pump inhibition by dopamine or PTH-(1-34) was abolished by staurosporine but not by IP20. The PLA2 inhibitor mepacrine prevented the effect of all agents, and arachidonic acid produced a dose-dependent pump inhibition in each of the three segments studied. We conclude that intracellular mechanisms of Na-K-ATPase regulation differ along the nephron, as they involve activation of PKA in CCD and MTAL and of PKC in PCT. These two pathways probably share a common mechanism in stimulating PLA2, arachidonic acid release, and production of eicosanoids in both the proximal and distal nephron. PMID- 8214100 TI - Regulation of intracellular pH in two cell populations of inner stripe of rabbit outer medullary collecting duct. AB - The inner stripe of the outer medullary collecting duct (OMCDis) is a major site of HCO3- reabsorption and urinary acidification. Whether this nephron segment consists of a single or multiple cell types remains unclear. Apical incubation of rabbit OMCDis via luminal perfusion with 2',7'-bis(2-carboxyethyl)-5(6) carboxyfluorescein acetoxymethyl ester resulted in heterogeneous fluorescence, suggesting two cell types. This heterogeneity was not prevented by inhibition of either carbonic anhydrase or organic anion transport. Subsequent studies were directed at characterizing the major intracellular pH (pHi) regulatory transporters in these two cell populations. Both cell populations demonstrated similar rates of Na+/H+ exchange, as assessed by peritubular Na(+)-dependent, amiloride-sensitive pHi recovery from an intracellular acid load. In contrast, Na(+)-independent, HCO3(-)-independent pHi recovery from an acid load was present in both cell populations but had two to three times greater activity in a minority cell population. In vivo deoxycorticosterone acetate administration increases this rate in both populations but to a greater extent in the minority cell population. In CO2/HCO3(-)-containing solutions, Cl- removal from the peritubular solution caused 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid sensitive alkalinization of all cells. Again, the magnitude and rate of alkalinization were significantly greater in the minority cell population. These studies demonstrate that the OMCDis consists of qualitatively similar cells in different states of functional activity. Although they are similar in most characteristics, a minority of cells more actively secrete H+ (independent of Na+) and reabsorb HCO3-. PMID- 8214102 TI - Endogenous EGF as a potential renotrophic factor in ischemia-induced acute renal failure. AB - The time course for the increases in soluble renal epidermal growth factor (EGF) after ischemia has been established. These elevated levels of EGF have been compared with the degree of tissue injury as well as the extent of cell proliferation in the recovering tissue. Levels of soluble immunoreactive EGF (irEGF) in control animals were 9.74 +/- 1.1 ng/g wet wt (n = 4-8 for all values) and rose to 83.9 +/- 30 ng/g within 12 h after injury. Soluble irEGF content peaked at 88.8 +/- 15 ng/g at 24 h postinjury and returned to control values by 72 h. We previously reported that trypsin digestion of crude renal membranes (CRM) generates rat EGF that is indistinguishable from that isolated from the submandibular gland. Initial levels of trypsin-releasable membrane-associated irEGF were 439 +/- 26 ng/g. These levels fell to 46.6 +/- 9.6 ng/g at 48 h after injury. The total renal EGF demonstrated an 80% decline 48 h after injury but returned to 50% of the initial values after 72 h representing significant new synthesis of EGF-containing proteins between 48 and 72 h postinjury. Immunohistochemical staining of kidney paraffin sections for EGF immunoreactivity demonstrated staining intensities that paralleled the amount of irEGF in the trypsin-digested CRM fraction, suggesting that the membrane-associated irEGF is the predominant form detected by this technique. Regenerative hyperplasia subsequent to tubular insult was monitored by immunostaining nuclei of S phase cells after pulse labeling with the thymidine analogue 5-bromo-2'-deoxyuridine. Cell proliferation was particularly prominent in the outer stripe of outer medulla of kidneys exposed to ischemia and reached a maximum (19-fold higher than the baseline value) 48 h after reperfusion. Renal cell turnover returned to control values by day 7. The observation that the peak in soluble EGF levels (24 h) precedes the peak in tubular regeneration (48 h) by 24 h is consistent with the hypothesis that EGF is one of the mitogenic signals triggering regenerative hyperplasia after renal injury. PMID- 8214101 TI - An osmotically tolerant inner medullary collecting duct cell line from an SV40 transgenic mouse. AB - The terminal inner medullary collecting duct (IMCD) plays an important role in determining the final urinary composition. Currently, there is no continuous cell line derived from this nephron segment. We have developed a cell line derived from the terminal IMCD of mice transgenic for the early region of simian virus SV40 (large T antigen). This cell line, mIMCD-3, retains many differentiated characteristics of this nephron segment including high transepithelial resistance (1,368 +/- 172 omega.cm2), inhibition of apical-to-basal sodium flux by amiloride (41 +/- 7%) and by atrial natriuretic peptide (ANP) (40 +/- 9%), the presence of the amiloride-sensitive sodium channel as determined by Western blot analysis, and accumulation of the major organic osmolytes in response to hypertonic stress. Significantly, mIMCD-3 cells adapted readily and were able to grow in hypertonic medium supplemented with NaCl and urea up to 910 mosmol/kgH2O. These extreme osmotic conditions exist in the renal medulla in vivo but are known to be lethal to most other cells. This cell line should be highly useful for the study of the cellular adaptation to osmotic stress and the cell biology and transport physiology of this nephron segment. PMID- 8214103 TI - Gentamicin-induced mobilization of iron from renal cortical mitochondria. AB - Iron, presumably by participating in generation of hydroxyl radical or other oxidant species or initiation of lipid peroxidation, has been shown to play an important role in several models of tissue injury, including acute renal failure induced by the antibiotic gentamicin. However, the sources of iron remain unknown. Rat renal mitochondria incubated at 37 degrees C with gentamicin resulted in a time- (15-60 min) and a dose-dependent (0.01-5 mM) iron release as measured by formation of iron-bathophenanthroline sulfonate complex FeII-(BPS)3 [at 60 min, control: 1.2 +/- 0.1 nmol/mg protein, n = 7; gentamicin (5 mM): 5.1 +/- 0.4 nmol/mg protein, n = 7]. No formation of FeII(BPS)3 complex was detected in the absence of mitochondria or when incubations were carried out at 0 degrees C. Similar results were obtained when 2,2'-dipyridyl, another iron chelator, was used for measurement of iron release. On the basis on our previous study that gentamicin enhances generation of hydrogen peroxide by renal cortical mitochondria, we examined whether effect of gentamicin on iron release is mediated by hydrogen peroxide. Catalase (which decomposes hydrogen peroxide), but not heat-inactivated catalase, as well as pyruvate, a potent scavenger of hydrogen peroxide, prevented gentamicin-induced iron mobilization. Superoxide dismutase, a scavenger of superoxide anion, or hydroxyl radical scavengers (dimethylthiourea or sodium benzoate) had no effect. Taken together, the data with scavengers indicate that gentamicin-induced iron mobilization from mitochondria is mediated by hydrogen peroxide. PMID- 8214104 TI - Acute phosphate depletion inhibits the Na+/H+ antiporter in a cultured renal cell line. AB - We studied the effect of acute Pi depletion on the regulation of intracellular pH (pHi) in the OK opossum kidney cell line by using the pH-sensitive dye 2'7' bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Cell recovery from an NH4Cl acid load in HCO3-free buffer disclosed an Na(+)-dependent component blocked by amiloride and a smaller Na(+)-independent component that increased on exposure of the cells to a high-K+ buffer. After 24-h incubation of the cells in phosphate free medium, pHi recovery by the Na+/H+ exchanger was markedly inhibited, whereas the Na(+)-independent pHi recovery was not affected. The inhibition of Na+/H+ exchange was reversible on correction of cellular Pi deficit. A similar phenomenon was observed when cellular Pi depletion was induced by acute exposure (min) to fructose. Pi depletion shifted the pHi dependence of the exchanger and also reduced its maximal activity. Time-course studies revealed that the effect of Pi depletion could not be attributed to attenuation of Na(+)-K(+) adenosinetriphosphatase activity and resultant diminution of the transmembrane gradient for the Na+ influx. We conclude that acute Pi depletion in cultured proximal tubular cells leads to reversible inhibition of the Na+/H+ exchanger. This in vitro finding may relate to the in vivo observation of impaired HCO3 reabsorption and bicarbonaturia in acute Pi depletion. PMID- 8214105 TI - Localization of central pressor action of bradykinin in medulla oblongata. AB - The intracerebroventricular injection of bradykinin produces an increase in arterial blood pressure. The site of action for this effect has been reported to be in the lateral septal area, in the hypothalamus, or in the ventral portion of the third ventricle. Bradykinin injected into the fourth cerebral ventricle of unanesthetized rats produced a pressor effect with a shorter latency and a larger maximal effect than when injected in the third or lateral ventricles. Bradykinin in the fourth ventricle was also 10 times more potent than in the third ventricle and 100 times more potent than in the lateral ventricle. No changes in blood pressure were observed when bradykinin was injected into the cerebellum or in the subarachnoid space of the ventral surface of the brain or of the medulla. Microinjections in the medulla oblongata showed that the pressor responses were obtained when bradykinin was injected in the nucleus tractus solitarius or in the dorsal spinal trigeminal tract. No effect was observed after injections were given into the ventral, ventral lateral medulla, or other medullary regions. The data suggest that bradykinin may play a regulatory role in the central control of blood pressure by stimulating sites that are near the dorsal and dorsal lateral surfaces of the medulla and accessible to kinins in cerebrospinal fluid and in the cerebral arterial circulation. PMID- 8214106 TI - Validity of thermal dilution technique for measurement of cardiac output in rats. AB - The validity of the thermal dilution technique for the measurement of cardiac output was verified in experiments on a circulation model and on anesthetized rats under open- and closed-chest conditions. In the circulation model thermal dilution was compared with direct (Fdir) and electromagnetic (F(elm)) flowmetry. Flow values measured in the circulation model with the thermal dilution (Fth) technique correspond well with direct flowmetry (Fth = 0.92 Fdir + 7.0; r = 0.888) and with electromagnetic flowmetry (Fth = 0.95 F(elm) + 1.2; r = 0.990). In the anesthetized rat cardiac output was determined with thermal dilution and simultaneously with Fick's method and/or with electromagnetic flowmetry. Fick's method and electromagnetic flowmetry resulted in identical cardiac output values (COFick = 0.95 COelm; r = 0.865), whereas the thermal dilution technique yielded unequivocally higher values. The extent of overestimation is much more pronounced at low cardiac output than at a high output. The study clearly demonstrates that this overestimation is due to heat diffusion, which is obviously of greater significance in small animals than in large animals or humans. Therefore, the thermal dilution technique is not appropriate for the measurement of cardiac output in the rat. PMID- 8214107 TI - Tyrosine kinase inhibitors suppress endotoxin- and IL-1 beta-induced NO synthesis in aortic smooth muscle cells. AB - Nitric oxide (NO) formation via the expression of an endotoxin- and cytokine inducible NO synthase (iNOS) within the vascular smooth muscle is thought to be responsible for the cardiovascular collapse that occurs during septic shock and antitumor therapy with cytokines. Because the molecular mechanisms that underlie induction of iNOS are still unclear and because tyrosine kinases are implicated in interleukin-1 beta (IL-1 beta)-induced prostaglandin synthesis in mesangial cells and in NO generation by an insulinoma cell line, we investigated the influence of tyrosine kinase inhibitors on iNOS induction in cultured rat aortic smooth muscle cells (RASMC). The production of biologically active NO was demonstrated by L-arginine-dependent guanosine 3',5'-cyclic monophosphate (cGMP) accumulation after a 3-h exposure to either IL-1 beta or lipopolysaccharide (LPS). Pretreatment of RASMC for 30 min with the tyrosine kinase inhibitor genistein prevented both IL-1 beta- and LPS-elicited cGMP accumulation in a concentration-dependent manner. Geldanamycin, a chemically different tyrosine kinase inhibitor, also blocked cGMP formation in response to both LPS and IL-1 beta at nanomolar concentrations. Genistein and geldanamycin inhibited cGMP accumulation even when added 90 min after LPS exposure, but no inhibition was observed when they were included at later time points (120-180 min), suggesting that the inhibitors had no direct effect on iNOS activity after its induction. Formation of cGMP in response to sodium nitroprusside and to NO released from bovine aortic endothelial cells remained virtually unaffected by genistein and geldanamycin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214108 TI - Differential actions of cAMP on endothelial [Ca2+]i and permeability in microvessels exposed to ATP. AB - We investigated the hypothesis that one of the actions of adenosine 3',5'-cyclic monophosphate (cAMP) to attenuate agonist-induced increase in microvessel permeability is to reduce the initial increase in endothelial cell cytoplasmic Ca2+ concentration ([Ca2+]i). ATP (10 microM) was used to increase hydraulic conductivity (Lp) and [Ca2+]i in venular microvessel in frog mesentery. The cAMP analogue, 8-bromo-cAMP (8-BrcAMP, 2 mM) significantly attenuated the initial increase in Lp (from a peak increase of 7.1 +/- 2.4 times control with ATP alone to 1.2 +/- 0.34 times control with ATP and cAMP). In contrast, cAMP did not significantly change the magnitude or time course of the biphasic increase in [Ca2+]i, which increased from 54 +/- 5 nM to peak of 187 +/- 48 nM with ATP alone, and from 55 +/- 8 nM to 190 +/- 28 nM with ATP and cAMP. Thus the action of cAMP to attenuate microvessel permeability increase in the presence of ATP does not involve modification of the initial Ca2+ transient in endothelial cells. Our results enable alternative hypotheses, such as the suggestion that cAMP might modulate a Ca(2+)-calmodulin-dependent actin-myosin cascade, to be investigated without the added complications of having to account for the modulation of initial changes in [Ca2+]i. Our data also demonstrate, for the first time in the endothelial cells of intact microvessels, that an increase in [Ca2+]i is not always associated with an increase in microvessel permeability. PMID- 8214109 TI - Rapid expression of the Na(+)-Ca2+ exchanger in response to cardiac pressure overload. AB - This report identifies a rapid increase in the expression of cardiac Na(+)-Ca2+ exchanger mRNA in response to an acute pressure overload. This enhanced exchanger expression appeared within 1 h after the onset of right ventricular pressure overload in the cat and was sustained during cardiac overloading for at least 4 h. Maintenance of this right ventricular pressure overload for 48 h evoked an increase in the production of exchanger protein. Because of our previous finding that load imposition on the heart initiates cell growth and our hypothesis that this is in response to the enhanced entry of cellular cations, we then examined the effect of Na+ influx into cultured adult cardiac myocytes, or cardiocytes, in terms of early anabolic responses. Pressure overload of the heart and cardiocyte Na+ influx were found to produce a common, rapid result in terms of both enhanced Na(+)-Ca2+ exchanger expression and accelerated synthesis of general and contractile proteins, the hallmarks of cardiac hypertrophy. PMID- 8214110 TI - TBA test and "free" MDA assay in evaluation of lipid peroxidation and oxidative stress in tissue systems. PMID- 8214111 TI - Role of sympathetic nerves in the vascular effects of local temperature in human forearm skin. AB - The role of adrenergic nerve function in the cutaneous vascular response to changes in local skin temperature in the human forearm was examined using three protocols: 1) blocking release of norepinephrine presynaptically by local iontophoresis of bretylium (BT), 2) altering background adrenergic tone by changing whole body skin temperature, and 3) blocking cutaneous nerves by proximal infiltration of local anesthetic. Forearm skin blood flow was measured by laser-Doppler flowmetry (LDF) and cutaneous vascular conductance (CVC) was calculated as LDF/blood pressure. In protocol 1, local cooling (29 degrees C) elicited a rapid and sustained fall in CVC at control sites (-43 +/- 8%) in contrast to a biphasic response at BT-treated sites, consisting of an initial vasodilation followed by a vasoconstriction (percent change CVC = 28 +/- 13 and 34 +/- 18, respectively). Local warming (39 degrees C) increased CVC at control and at BT-treated sites by 331 +/- 46 and 139 +/- 31%, respectively. In protocol 2, at a neutral, cool, or warm whole body skin temperature, local cooling (29 degrees C) elicited similar reductions in CVC (-34 +/- 8, -29 +/- 5, and -30 +/- 4%, respectively), and local warming (38 degrees C) produced similar increases in CVC (89 +/- 15, 85 +/- 21, and 74 +/- 22%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214112 TI - Variable effects of endothelin-1 on [Ca2+]i transients, pHi, and contraction in ventricular myocytes. AB - We examined the effects of endothelin-1 (ET-1) on intracellular free calcium concentration ([Ca2+]i) transients, intracellular pH (pHi), and cell contraction in both embryonic and neonatal as well as in adult ventricular myocytes. Exposure of chick ventricular myocytes to ET-1 (10 nM) significantly decreased both peak systolic and end-diastolic [Ca2+]i (from 949 +/- 43 to 628 +/- 59 nM and from 230 +/- 13 to 162 +/- 8 nM, respectively; P < 0.05, n = 12). The amplitude of cell contraction was also decreased during exposure to 10 nM ET-1 (81.7 +/- 1.2% of control, P < 0.01, n = 12). Exposure to 10 nM ET-1 slightly decreased pHi (-0.055 +/- 0.020 U; P < 0.05). Exposure of cultured neonatal rat ventricular myocytes to ET-1 (10 nM) produced similar effects. Responses of adult rabbit ventricular myocytes to ET-1 were dramatically different from those of embryonic or neonatal ventricular myocytes. Exposure to 10 nM ET-1 increased the amplitude of cell contraction to 159 +/- 32% of control (P < 0.01) without an increase in [Ca2+]i transients. ET-1 also increased pHi (+0.081 +/- 0.047 U; P < 0.01). These results indicate that ET-1 produces a negative inotropic effect by decreasing [Ca2+]i transients and induces a slight intracellular acidosis in immature ventricular myocytes. However, ET-1 causes a positive inotropic effect in adult ventricular myocytes via an intracellular alkalinization, rather than by an increase in the [Ca2+]i transient. Thus the response of myocytes to vasoactive peptides may vary with development and/or species. PMID- 8214114 TI - Temporal sequence of endotoxin-induced systolic and diastolic myocardial depression in rabbits. AB - Twelve anesthetized rabbits received endotoxin (175 +/- 38 micrograms/kg i.v., mean +/- SD) to evaluate the temporal sequence of alterations in left ventricular (LV) function. LV volume was calculated from LV minor- and long-axis diameters, and wall thickness was measured with sonomicrometers. Hypotension, acidosis, and hypoxia were immediately corrected to eliminate these causes of myocardial depression. LV dilation developed early (1.2 +/- 0.5 h) with a significant (21 +/ 23%) increase in end-diastolic volume measured at a LV end-diastolic pressure of 5 +/- 6 mmHg. The LV stiffness did not change, and the LV dilation did not progressively worsen. Significant systolic depression developed later (2.8 +/- 1.0 h) with a 32 +/- 22% increase in end-systolic volume measured at a LV end systolic pressure of 69 +/- 9 mmHg. The late preterminal phase (4.1 +/- 0.8 h) was characterized by a progressive increase in end-systolic volume (73 +/- 41% above control) and a significant (53 +/- 34%) increase in tau, the time constant of LV pressure fall. Diastolic abnormalities (LV dilation and increased tau) were not attributable to depressed contractility or altered hemodynamics. We conclude that endotoxin impairs systolic and diastolic LV function with distinct differences in time course. This suggests that contractility, relaxation, and passive LV properties are impaired by different endotoxin-mediated pathways and/or have different sensitivities to endotoxin. PMID- 8214113 TI - Impaired regional subendocardial coronary flow reserve in conscious dogs with pacing-induced heart failure. AB - The purpose of the present investigation was to examine coronary flow and vasodilator reserve in conscious, chronically instrumented dogs with pacing induced heart failure, a model of severe biventricular cardiomyopathy devoid of significant hypertrophy. Twelve dogs were studied after 28 days of rapid right ventricular pacing and were compared with six sham-operated controls. Left ventricular (LV) average transmural flow was significantly less in conscious dogs with pacing-induced heart failure, whereas the endocardial-to-epicardial flow ratio was not significantly different. In response to near maximal coronary vasodilation with adenosine, subepicardial coronary flow and vasodilator reserve were preserved in congestive heart failure (CHF), yet there was evidence of impaired subendocardial flow and vasodilator reserve, and the endocardial-to epicardial ratio was significantly less. When the markedly elevated LV end diastolic pressure was normalized in heart failure, there was restoration of subendocardial coronary flow reserve and a normalization of the endocardial-to epicardial ratio. Thus, in CHF, there is impaired coronary flow and vasodilator reserve that is selective to the subendocardium of the LV. At this point in the heart failure process, this impairment is not associated with structural changes but is a consequence of the marked elevation in LV end-diastolic pressure. PMID- 8214115 TI - Effect of an increase in systemic blood pressure on nailfold capillary pressure in humans. AB - Moderate autoregulation of capillary pressure occurs during changes in arterial and/or venous pressure in animals. Whether an increase in systemic blood pressure is transmitted to capillaries in humans is unknown. Eight healthy volunteers performed isometric handgrip exercise (30% of maximum) while nailfold capillary pressure (CP) and digital arterial blood pressure (DBP) were measured in the contralateral hand. CP was measured for 40 s before exercise and 40-100 s during exercise. Only experiments with no change in pipette position and no artifactual changes in flow were accepted. Basal DBP was stable [91.5 +/- 12.7 mmHg (-40 to 20 s basal) and 91.3 +/- 11.8 mmHg (-20 to 0 s basal)], and isometric exercise increased DBP [100.4 +/- 13.9 mmHg (0-20 s exercise) and 103.1 +/- 15.3 mmHg (20 40 s exercise); P < 0.05]. CP was unchanged during the first 40 s of exercise [18.9 +/- 4.9 mmHg (-40 to 20 s basal), 18.9 +/- 5.2 mmHg (-20 to 0 s basal), 18.4 +/- 4.7 mmHg (0-20 s exercise), and 18.3 +/- 5.3 mmHg (20-40 s exercise)] and remained unchanged for up to 100 s (n = 5), despite a continued elevation of DBP. These data suggest that protective mechanisms minimize the transmission of increases in systemic blood pressure to the capillary bed in humans. PMID- 8214116 TI - Selective brain cooling increases cortical cerebral blood flow in rats. AB - To evaluate the effect of selective brain cooling on cortical cerebral blood flow, we reduced brain temperature in nitrous oxide anesthetized adult rats using a high speed fan while keeping rectal temperature at 37-38 degrees C. During selective brain cooling, cortical cerebral blood flow, as measured by laser Doppler flowmetry, increased to 215 +/- 26% (mean +/- SE) of baseline at a cortical brain temperature of 30.9 +/- 0.5 degrees C and a rectal temperature of 37.5 +/- 0.1 degrees C. During rewarming, as brain temperature increased, cortical cerebral blood flow decreased. The cerebral vasodilatory response to hypothermia may explain its protective effects during and after cerebral ischemia. PMID- 8214117 TI - Use of 2,3-butanedione monoxime to estimate nonmechanical VO2 in rabbit hearts. AB - The purpose of the present study was to evaluate the feasibility of partitioning myocardial O2 consumption (VO2) into mechanical and nonmechanical components in the whole heart preparation using a negative inotrope, 2,3-butanedione monoxime (BDM), which has been reported to have a selective effect on the contractile proteins in a low concentration range (< 6 mM). In six isolated bovine red blood cell-perfused rabbit hearts, VO2 and force-time integral (FTI) were measured during infusion of varying concentrations of BDM at a constant left ventricular volume chosen such that control left ventricular peak isovolumic pressure was approximately 100 mmHg. The VO2-FTI relation with BDM concentrations < or = 5 mM was highly linear (median r = 0.98). Its VO2-axis intercept at zero FTI had a positive value (mean 23% of control, 0.014 ml O2.beat-1 x 100 g-1). To confirm the selective effect of BDM on the contractile proteins, the intracellular free Ca2+ transient was measured with the fluorescent indicator indo 1 in three isolated buffer-perfused rabbit hearts. The amplitude of the Ca2+ transient was not altered by BDM at concentrations < or = 10 mM, although left ventricular developed pressure was markedly depressed. This finding indicates that BDM < or = 10 mM does not affect excitation-contraction coupling. We conclude that the VO2 axis intercept value of the VO2-FTI relation during BDM infusion in a low concentration range represents VO2 for nonmechanical energy utilization. The BDM method to partition VO2 into mechanical and nonmechanical components is thus feasible in the whole rabbit heart. PMID- 8214118 TI - Changes in rat mesentery interstitial matrix due to superfusate. AB - Animal preparations for microscopy often require a superfusate solution to cover surgically exposed tissue. There are few, if any, data concerning the effects of this solution on extravascular protein concentration and hydration. The effect of superfusion on mesenteric tissue in anesthetized male Sprague-Dawley rats was studied. Tissue samples were taken from nonsuperfused and superfused tissue and analyzed for hydration, albumin, and transferrin content. The mesenteric tissue interstitial matrix was rapidly altered by normal saline superfusate. After superfusion, there was a decrease (P < 0.01) in tissue albumin concentration from 1.17 +/- 0.27 to 0.10 +/- 0.08 g/dl (n = 9). Tissue hydration increased from 4.98 +/- 0.8 micrograms water/microgram dry wt in controls to 7.38 +/- 1.2 micrograms water/micrograms dry wt after superfusion. When a range of superfusate albumin concentrations was used (0, 1, 2, and 3 g/dl), tissue albumin concentration changed 0.59 +/- 0.09 g/dl for each gram per deciliter change in superfusate concentration (P < 0.0001). The large changes in interstitial matrix protein content and hydration suggest that superfusate solution effects need to be considered in microvascular protein transport experiments. PMID- 8214119 TI - Hyperpolarization of in situ rat saphenous vein in response to axial stretch. AB - The goal of this study was to measure the effect of axial stretch on vascular smooth muscle (VSM) transmembrane potential (Em) and external diameter (De) of intact and deendothelialized rat saphenous veins (SV). Incremental increases in length of SV were produced in situ by biaxial stretch of its perivascular connective tissue. Em was measured in situ with glass microelectrodes and De with a high-resolution eyepiece or on-line video microangiometer. Vessels were locally denervated by 20 min superfusion with 6-hydroxydopamine. Endothelium was removed by maintaining an air bolus in the lumen for 6 min. Axial stretch of endothelium intact SV from a baseline length (Lo, at which there was no vessel buckling or folding) to 120% Lo induced a small depolarization from -56 +/- 1.2 to -53 +/- 0.8 mV. This was followed by a substantial hyperpolarization to -65 +/- 1.4 mV at 140% Lo. However, a depolarization was observed in deendothelialized SV from -47 +/- 1.3 mV at Lo to -43 +/- 1.8 mV at 140% Lo. Neither Em response was influenced by local denervation. Relative to Lo, 40% stretch also attenuated norepinephrine induced vasoconstriction. These results suggest that axial stretch of SV can lead to release of endothelium-derived factor(s) that hyperpolarizes venous VSM and possibly attenuates stretch-induced and adrenergic vasoconstriction. Such a response may act as a protective mechanism to attenuate vasoconstriction induced by axial stretch. PMID- 8214120 TI - Nitric oxide prevents leukocyte adherence: role of superoxide. AB - The objective of this study was to determine whether the antiadhesive effects of NO for leukocytes are related to its ability to scavenge superoxide in vivo. Intravital microscopy was used to monitor leukocyte adherence and flux as well as velocity and number of rolling leukocytes in 25- to 40-microns venules. The superoxide-generating system, hypoxanthine and xanthine oxidase (HX-XO), was infused into the mesenteric circulation in untreated animals and in animals pretreated with either superoxide dismutase (SOD) or the NO donor, SIN 1. In another series of studies, the mesenteric preparation was superfused with either platelet-activating factor (PAF) or leukotriene B4 (LTB4) followed by the administration of either SIN 1 or SOD. HX-XO infusion caused a significant increase in the number of rolling and adherent leukocytes (responses that were entirely inhibited by SOD or SIN 1). SOD and SIN 1 both attenuated the PAF induced but not the LTB4-induced leukocyte adherence. The observation that both SOD and SIN 1 inhibit leukocyte adhesion only under conditions associated with superoxide formation (HX-XO and PAF, but not LTB4) strongly suggests that the antiadhesion properties of NO are related to its ability to inactivate the superoxide anion. PMID- 8214121 TI - Resistance to O2 diffusion in anemic red muscle: roles of flux density and cell PO2. AB - Normal and anemic dog gracilis muscles were compared at equal O2 uptake rates (VO2) to locate the principal site of resistance to diffusive O2 transport. Anemia halved the hematocrit and the number of red blood cells per square millimeter of muscle cross section. Flow doubled in anemia, and flow times arterial O2 content, PO2 of effluent blood, and O2 extraction per red blood cell were approximately the same as control. Nevertheless, intracellular PO2 was significantly lower in anemia. At any instant the aggregate red blood cell surface area for O2 release was about half normal. Because the flux (VO2) was the same as control, the driving force for diffusion from red blood cell to myocyte should have doubled. An estimate of the total driving force from red blood cell to mitochondria was greater in anemia. This increase was much less than a factor of 2 because lower intracellular PO2 increases myoglobin-facilitated diffusion, thus decreasing resistance inside the myocyte. The role of myoglobin and the coupling of convective to diffusive transport are discussed. We conclude that the principal resistance to O2 diffusion lies outside the myocyte. PMID- 8214122 TI - Adenosine and insulin mediate glucose uptake in normoxic rat hearts by different mechanisms. AB - The effect of adenosine (ADO) and its interaction with insulin (I) on myocardial glucose uptake was evaluated in the normoxic isolated rat heart using 2 [3H]deoxyglucose. Isovolumic hearts were perfused at constant flow with a nonrecirculating bicarbonate buffer containing 5.5 mM glucose as the sole substrate. After a 30-min equilibration period, the glucose and extracellular ([14C]sucrose) tracers were infused for 15 min before initiation of the 15-min experimental period. Both 100 microM ADO and 4 mU/ml I significantly increased glucose uptake (GU) compared with control values (in mumol.min-1 x g-1: ADO = 0.34 +/- 0.03, I = 0.44 +/- 0.03, control = 0.23 +/- 0.02; P < 0.05). In combination, ADO and I produced an additive increase in GU (0.54 +/- 0.03; P < 0.05 vs. control). The mechanism of enhanced GU by ADO and I was investigated with the glucose uptake inhibitors phloridzin (PZ) and phloretin (PT), each of which has a unique site of action on the cell membrane. ADO-mediated GU was completely blocked by 3 mM PZ (ADO + PZ = 0.20 +/- 0.01; P = NS vs. control), but I-stimulated GU was unaffected (I + PZ = 0.38 +/- 0.03; P = NS vs. I). Only GU attributable to ADO was blocked by PZ infused with ADO and I (ADO + I + PZ = 0.43 +/- 0.03; P = NS vs. I). Both ADO- and I-mediated GU were inhibited by 100 microM PT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214123 TI - Lack of modulation by dietary unsaturated fats on sympathetic neurotransmission in rat hearts. AB - We examined the effect of dietary polyunsaturated fatty acids (PUFA) on cardiac sympathetic neurotransmission. Rats were fed semisynthetic diets (18.5% fat wt/wt) high in saturated fatty acids (control diet), high in n-6 PUFA (corn oil), or enriched with n-3 PUFA (Maxepa). A perfused innervated heart model was used to examine different aspects of sympathetic neurotransmission 10 wk after the feeding. Dietary PUFA increased the content of n-6 or n-3 PUFA in myocardial phospholipids compared with animals fed control diets. Myocardial norepinephrine content, sympathetic nerve stimulation-induced norepinephrine release, neural reuptake, presynaptic alpha-adrenergic inhibition of norepinephrine release, and postsynaptic inotropic response (+/- dP/dt) to sympathetic nerve stimulation or to a beta-agonist were essentially not influenced by dietary PUFA. Neural norepinephrine release during prolonged ischemia (60 min) was also similar in hearts from rats fed n-6 PUFA and control diets. Thus a modification of sympathetic neurotransmission was not achieved by feeding PUFA-enriched diets for 10 wk. PMID- 8214124 TI - Norepinephrine levels in paraventricular nucleus of spontaneously hypertensive rats: role of neuropeptide Y. AB - Recent evidence supports the view that the sympathetic system actively participates in the development of hypertension. Because norepinephrine, contained within central neurons involved in cardiovascular sympathetic regulation, is known to coexist with neuropeptide Y, it is possible that a functional interaction between neuropeptide Y and norepinephrine exists within the brain. In an effort to clarify whether or not central catecholamine systems are modulated by neuropeptide Y in hypertensive situations, the paraventricular nucleus of spontaneously hypertensive rats was exposed to neuropeptide Y (10(-9) M), and levels of norepinephrine were sampled by microdialysis. Norepinephrine levels in spontaneously hypertensive rats were significantly increased and did not change after exposure to neuropeptide Y, in sharp contrast to the decreases seen in Wistar-Kyoto controls. To ascertain whether these alterations in norepinephrine control were specific to the model used, a similar series of experiments was carried out in the paraventricular nucleus of aortic-banded rats. These studies supported the previous findings. Norepinephrine levels in aortic banded rats were markedly elevated when compared with sham-operated controls and demonstrated no change after exposure to neuropeptide Y, whereas decreases of > 50% were seen in sham-operated controls. These results support the view that mechanisms normally involving neuropeptide Y as a neuromodulator in the paraventricular nucleus are altered in hypertensive situations. It is suggested that hypertension may precipitate changes in mechanisms involving brain neuropeptide Y and increased sympathetic activity. PMID- 8214125 TI - Impact of ejection on magnitude and time course of ventricular pressure generating capacity. AB - This study focuses on elucidating how ventricular afterloading conditions affect the time course of change of left ventricular pressure (LVP) throughout the cardiac cycle, with particular emphasis on revealing specific limitations in the time-varying elastance model of ventricular dynamics. Studies were performed in eight isolated canine hearts ejecting into a simulated windkessel afterload. LVP waves measured (LVPm) during ejection were compared with those predicted (LVPpred) according to the elastance theory. LVPm exceeded LVPpred from a time point shortly after the onset of ejection to the end of the beat. The instantaneous difference between LVPm and LVPpred increased steadily as ejection proceeded and reached between 45 and 65 mmHg near end ejection. This was in large part due to an average 35-ms prolongation of the time to end systole (tes) in ejecting compared with isovolumic beats. The time constant of relaxation was decreased on ejecting beats so that, despite the marked prolongation of tes, the overall duration of ejecting contractions was not greater than that of isovolumic beats. The results demonstrate a marked ejection-mediated enhancement and prolongation of ventricular pressure-generating capacity during the ejection phase of the cardiac cycle with concomitant acceleration of relaxation. None of these factors are accounted for by the time-varying elastance theory. PMID- 8214126 TI - Curvilinearity of LV end-systolic pressure-volume and dP/dtmax-end-diastolic volume relations. AB - We investigated the effect of contractile state (CS) on the curvilinearity of the left ventricular (LV) end-systolic pressure-volume (Pes-Ves) and the dP/dtmax-end diastolic volume (dP/dtmax-Ved) relations in eight anesthetized open-chest dogs. LV volume was determined from three orthogonal diameters measured by sonomicrometry. The Pes-Ves relation and dP/dtmax-Ved relation were assessed during transient vena caval occlusion and aortic constriction, while CS was altered with dobutamine. At all CS, both relations were linear when volumes were decreased by caval occlusion. However, at higher volumes obtained by aortic constriction, the relations became nonlinear. At enhanced CS, the nonlinearity of both the Pes-Ves relation and the dP/dtmax-Ved relation increased. The dP/dtmax Ved relation began to deviate from linearity at larger volumes, but closer to baseline operating volume, than the Pes-Ves relation. The relation between end systolic mean circumference stress and wall strain (sigma es-epsilon es) was linear at control CS when the Pes-Ves relation was nonlinear but became nonlinear with enhanced CS. We conclude that both the Pes-Ves relation and the dP/dtmax-Ved relation are nonlinear, saturating at higher volumes. With increased CS, the nonlinearity of both relations increases. This CS-dependent curvilinearity of the Pes-Ves relation is due to both CS-dependent nonlinearity of the sigma es-epsilon es relation (consistent with length-dependent activation) and geometric factors that alter the relation between Pes and sigma es. PMID- 8214127 TI - Carotid baroreflex responsiveness to lower body positive pressure-induced increases in central venous pressure. AB - Lower body positive pressure (LBPP) was applied at 4 and 30 Torr to increase central venous pressure (CVP). CVP increased with LBPP (r = 0.55, P < 0.01), and the increases were significant at 4 and 30 Torr (7.4 and 7.8 mmHg) from the control (6.0 mmHg). During LBPP cardiac output increased, which was significantly related to the increase in CVP (r = 0.63, P < 0.01). The carotid baroreflex was elicited by trains of neck pressure and suction from 40 to -65 Torr. The carotid cardiac and carotid-vasomotor baroreflex responses were assessed by determining the maximal gains of heart rate (HR) interval and intraradial mean arterial pressure (MAP) to changes in carotid sinus pressure using a logistic model. The carotid-cardiac and carotid-vasomotor baroreflex gains were negatively related to LBPP, and at 30 Torr, both gains (5.6 ms/mmHg and -0.14 mmHg/mmHg) were significantly smaller than the control (12.4 ms/mmHg and -0.24 mmHg/mmHg). The decreases in carotid-cardiac and carotid-vasomotor baroreflex sensitivity during LBPP were primarily associated with the increases in CVP (r = -0.52, P < 0.01, and r = -0.74, P < 0.01, respectively). These data suggest that the increases in CVP and/or central blood volume diminish the sensitivity of the carotid baroreflex control of HR and MAP by enhancing the tonic inhibitory influence from the cardiopulmonary baroreceptors. PMID- 8214128 TI - Glomerular atrial natriuretic factor receptors in experimental congestive heart failure. AB - Heart failure is usually characterized by a relative insensitivity to atrial natriuretic factor (ANF). Downregulation of ANF receptors has been reported but remains controversial. Renal response to ANF infusion, glomerular ANF receptors, and guanosine 3',5'-cyclic monophosphate (cGMP) production have been studied in rabbits with congestive heart failure (CHF) after traumatic aortic regurgitation and abdominal aortic stenosis. Diuresis and natriuresis induced by ANF infusions were significantly decreased in CHF animals. Plasma cGMP was higher in CHF rabbits before ANF administration than in controls (37.6 +/- 7.2 vs. 17.1 +/- 3.9 pmol/ml, P < 0.02) and increased to a same level after ANF in both groups (48.8 +/- 4.2 vs. 52.5 +/- 2.8 pmol/ml, NS). No difference was found in glomerular ANF receptor density (436 +/- 54 vs. 425 +/- 57 fmol/mg protein, NS) nor in affinity between the two groups (dissociation constant; 240 +/- 24 vs. 347 +/- 49 pM, NS). Moreover, in vitro glomerular cGMP production in response to exogenous ANF was preserved. In conclusion, despite a blunted renal response to ANF in vivo, glomerular ANF receptors were unchanged in this model, and no defect in cGMP production in response to ANF was found. This suggests the existence of an intracellular defect beyond the second messenger. PMID- 8214129 TI - Monkey cerebral arterial relaxation caused by hypercapnic acidosis and hypertonic bicarbonate. AB - In helical strips of Japanese monkey cerebral arteries contracted with vasoconstrictors, applications of high CO2 (15% compared with 5% CO2 in control media) and hypertonic NaHCO3 (50 mM) produced relaxations. Similar relaxations were also obtained in human cerebral arterial strips. Hypercapnia increased PCO2 and resulted in acidosis in the bathing media, and the addition of NaHCO3 restored the pH to normal with high PCO2 and increased the osmotic pressure. The relaxant responses were not influenced by endothelium denudation and treatment with indomethacin. The hypercapnia-induced relaxation was suppressed by ouabain but was unaffected by amiloride. On the other hand, hypertonic bicarbonate induced relaxations were inhibited by ouabain as well as by amiloride. Removal of Na+ from the bathing media abolished the hypercapnia-induced relaxation but did not alter the hyperosmolar relaxation. In contrast to hypertonic NaHCO3, isotonic bicarbonate solutions contracted the arterial strips by neutralizing the pH under hypercapnia. It may be concluded that relaxations elicited by hypercapnic acidosis are associated with a fall of extracellular pH and an activation of the electrogenic Na+ pump, and those caused by hyperosmolarity are due to stimulation of the Na(+)-H+ exchange and the Na+ pump. Endothelium-derived vasoactive substances and cyclooxygenase products do not appear to be involved in these relaxations of monkey cerebral arteries under the experimental conditions used. PMID- 8214131 TI - Nitric oxide does not mediate the attenuated pulmonary vascular reactivity of chronic pneumonia. AB - Chronic Pseudomonas pneumonia is associated with decreased acute hypoxic pulmonary vasoconstriction. However, it is not known whether this is a result of a generalized reduction in contractile responsiveness. We therefore examined the effect of chronic Pseudomonas pneumonia on in vitro pulmonary vascular responsiveness to agonists. We then investigated the role of nitric oxide (NO) in the altered pulmonary vascular contractility. Control rats or rats infected with Pseudomonas (pneumonia) were killed, and small intrapulmonary arteries (100-200 microns effective lumen radius) were removed. In the pneumonia group, arteries were harvested from the pneumonic area of the lung. Vascular responsiveness was assessed in vitro by obtaining cumulative dose-response curves to contractile agonists [phenylephrine (PE), 5-hydroxytryptamine (5-HT), prostaglandin F2 alpha (PGF2 alpha), and KCl]. KCL-induced (voltage-operated) contractions were not significantly depressed in small pulmonary arteries from pneumonic lungs, suggesting that the smooth muscle contractile apparatus in these arteries was preserved. Contractile responses to the three receptor-operated agonists (PE, 5 HT, and PGF2 alpha) were significantly depressed in arteries subserving the pneumonic lobe of infected rats. NG-monomethyl-L-arginine, which blocks the synthesis of NO, caused a shift toward the left in the dose-contraction curves to PE, PGF2 alpha, and 5-HT in vessels from the sterile control lungs, but it had little effect on arteries from the pneumonic lungs. Chronic Pseudomonas pneumonia is associated with depressed pulmonary vascular contractility in vitro, particularly affecting the receptor-mediated contractile responses. Excessive NO release does not contribute to this attenuated vascular contractility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214130 TI - Ejecting deactivation does not affect O2 consumption-pressure-volume area relation in dog hearts. AB - We studied the effects of ejection velocity and resistive properties of the left ventricle (LV) on myocardial oxygen consumption (VO2) in 13 excised cross circulated dog hearts. Increases in peak ejection velocity (-dV/dt) from 4.0 +/- 1.3 (SD) end-diastolic volume (EDV)/s to 12.7 +/- 5.3 EDV/s with constant EDV and end-systolic volume (velocity run) induced systolic pressure deficit. This decreased pressure-volume area (PVA; a measure of ventricular mechanical energy) and LV end-systolic elastance (Emax) by 47 +/- 14 and 38 +/- 15%, respectively. Unchanged maximum rate of left ventricular pressure rise and time-varying elastance during the isovolumic contraction period at the same EDV indicated that these contractions started with the same contractile state although the quicker ejection caused the greater deactivation. If the PVA deficit due to systolic pressure deficit is attributable to an internal energy-dissipating resistive element, VO2 in the velocity run will not as much decrease in proportion to PVA as in the isovolumic or slowly ejecting control run. However, the decreases in PVA due to increased -dV/dt decreased VO2 to the same extent as in the control run. This result negated the possibility that the pressure and PVA deficits would be caused by a mechanical energy-losing process. The same results were obtained whether or not Emax was decreased by quick ejection. We conclude that the pressure and PVA deficits and the proportionally decreased VO2 during quick ejection are mainly attributable to suppression of a ventricular mechanical energy generation process, but not of mechanical energy-losing process, by ejecting deactivation. PMID- 8214132 TI - Postural vascular response in human skin: passive and active reactions to alteration of transmural pressure. AB - Laser-Doppler (LD) fluxmetry was performed in the palmar finger skin of healthy subjects to study the mechanisms contributing to the postural vascular response. Local transmural pressure in the skin blood vessels of the region studied was altered for 1 min in two experimental series either by passive movement of the arm to different vertical hand positions relative to heart level or by application of external pressure (-120-180 mmHg) to the finger. Heart and respiratory rate, arterial blood pressure, and LD flux in the contralateral finger (kept at heart level) were measured. The measurements suggest a compound reaction of local (myogenic) and systemic (neurogenic) mechanisms: the local regulatory component appears as a graded active vascular response elicited by passive vessel distension or compression. A systemic component, associated with a single deep inspiration, is frequently observed during the actual movement of the arm. In addition, prolonged holding of the test hand in a given vertical position also elicits a delayed vascular response in the control hand at heart level, which may be generated by volume receptors in the intrathoracic low-pressure system. PMID- 8214133 TI - Release of vasoactive intestinal peptide and neuropeptide Y from canine heart. AB - The effects of right cervical vagal and left sympathetic stimulation on release of immunoreactive vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) into cardiac venous and lymphatic effluent was tested in 11 anesthetized adult mongrel dogs. After stimulation of the right cervical vagus (1 ms, 20 Hz, 5 V) for 3 min, VIP output in lymphatic effluent was significantly increased at 1.90 +/- 0.56 pg/min compared with control of 0.90 +/- 0.42 pg/min. NPY output in lymphatic effluent and VIP and NPY release into coronary venous effluent, as measured by the arterial-coronary sinus concentration difference, were not changed. After stimulation of the ansae of the left sympathetic ganglion (1 ms, 10 Hz, 5 V) for 3 min, NPY output in lymphatic effluent was significantly increased at 4.72 +/- 1.58 pg/min compared with a control of 0.73 +/- 0.66 pg/min. VIP output in lymphatic effluent was not changed. VIP arterial-coronary sinus concentration difference decreased slightly but significantly, and NPY arterial-coronary sinus concentration difference decreased markedly after left sympathetic stimulation. In three additional dogs in which coronary sinus blood flow was measured, NPY overflow during left sympathetic stimulation increased from 28.2 +/- 23.5 to 129.6 +/- 212.7 pg/min. Thus VIP and NPY release from the canine heart can be evoked by right cervical vagal and left sympathetic stimulation, respectively. VIP and NPY may play a role as cardiac noncholinergic nonadrenergic neurotransmitters. PMID- 8214134 TI - Endothelial cell dysfunction occurs very early following trauma-hemorrhage and persists despite fluid resuscitation. AB - Although hemorrhage produces alterations in hemodynamics and cellular functions, it remains unknown if endothelial cell function is depressed in a nonheparinized model of trauma-hemorrhage and resuscitation. To study this, rats underwent a 5 cm midline laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleed-out volume was returned in the form of Ringer lactate (RL). They were then resuscitated with four times the volume of the shed blood with RL over 60 min. At the time of maximal bleed out (approximately 50 min from the onset of hemorrhage), 1.5, and 4 h after the completion of resuscitation, aortic rings (approximately 2.5 mm in length) were isolated and mounted in organ chambers. Dose responses for an endothelium-dependent vasodilator (acetylcholine) and endothelium-independent vasodilator (nitroglycerin) were determined. The results indicate that endothelium-dependent relaxation was depressed at the time of maximal bleed out and persisted even after resuscitation. However, there was no significant difference in nitroglycerin-induced relaxation at any point during the study period. In addition, hypoxia-induced contraction, a process mediated by endothelium-derived contracting factor, decreased significantly following hemorrhage and resuscitation. Thus endothelial cell dysfunction (i.e., reduced release of endothelium-derived relaxing and contracting factors) occurs very early after trauma-hemorrhage and persists despite fluid resuscitation. PMID- 8214135 TI - Antagonism of LTD4-evoked relaxation in canine renal artery and vein. AB - The goal of this study was to characterize further the manner in which the peptide leukotriene (LT) D4 evokes endothelium-dependent relaxation of the canine renal vein (RV) and artery (RA). The effects of four chemically and structurally dissimilar LT receptor antagonists and pertussis toxin (PTX), on LTD4-evoked relaxation of RV and RA rings, were determined and compared. In the presence of ICI 198,615 (10(-5) M), relaxation of both the RA and RV evoked by LTD4 was markedly attenuated. MK-571 (10(-5) M) altered neither RA nor RV relaxation evoked by LTD4. Relaxation of the RV but not the RA, evoked by LTD4, was attenuated in the presence of LY171,883 (10(-5) M). L649,923 (10(-5) M) solely inhibited LTD4-evoked relaxation of the RA. Pretreatment of vascular rings with PTX (250 ng/ml) for 2 h attenuated the vasomotor relaxation evoked by LTD4 in the RA but not in the RV. These observations suggest that LTD4-evoked relaxation of the RA and RV is dependent on different mechanisms. The endothelium-dependent response produced in the RA apparently involves a PTX-sensitive G protein. It is proposed that multiple signal transduction pathways and perhaps different LTD4 receptors may account for the diverse activity of LTD4. PMID- 8214136 TI - Arterial pressure-flow relationships in hypertensive dogs: effect of carotid sinus baroreflex. AB - The effect of the carotid sinus baroreflex reflex on arterial pressure-flow relationships was studied in Goldblatt hypertensive and normotensive dogs on cardiopulmonary bypass. Dogs were anesthetized with pentobarbital sodium, vagotomized, and the carotid sinuses were isolated at controlled carotid sinus pressures (CSP). The mean arterial pressure-flow relationships were measured at different levels of CSP. The arterial pressure-flow relationship was found to be linear except at extreme levels of flow. The slopes derived from the linear regression of the pressure-flow relationships [total peripheral resistance (TPR)] were 1.466 +/- 0.111 and 0.786 +/- 0.13 mmHg.ml-1 x min.kg at CSP of 50 and 200 mmHg in the normotensive group and 1.758 +/- 0.183 and 0.937 +/- 0.114 mmHg.ml-1 x min.kg at CSP of 50 and 250 mmHg in the hypertensive group. The increases in slope measured when CSP was decreased from saturation to threshold were 0.68 mmHg.ml-1 x min.kg (187% increase) in the normotensive group and 0.82 mmHg.ml-1 x min.kg (188% increase) in the hypertensive group. Zero-flow arterial pressures at CSP of 50, 125, and 200 mmHg were found to be 23.1 +/- 2.9, 21.7 +/- 2.2, and 17.1 +/- 1.8 mmHg in the normotensive group and 28.4 +/- 2.2, 23.8 +/- 1.5, and 20.0 +/- 1.2 mmHg in the hypertensive group. A nonlinear model fit was found to give a significantly better fit [coefficient of determination (r2) = 0.932 linear, 0.956 nonlinear] of the arterial pressure-flow relationships. We conclude that, in experimental hypertension, carotid baroreflex control of TPR is shifted to a higher operating point without any reduction in overall reflex gain. PMID- 8214137 TI - Cholecystokinin octapeptide analogues suppress food intake via central CCK-A receptors in mice. AB - To examine the mechanism of the satiety-producing effect of cholecystokinin (CCK) in the central nervous system, we compared the potency of intraperitoneally (ip) or intracerebroventricularly (icv) administered CCK-8 and its analogues on food intake in fasted mice. The icv administration of a small dose of CCK-8 (0.03 nmol/brain) or of Suc-(Thr28, Leu29, MePhe33)-CCK-7 (0.001 nmol/brain) suppressed food intake for 20 min, whereas CCK-8 (1 nmol/kg, which is equivalent to 0.03 nmol/brain) or Suc-(Thr28, Leu29, MePhe33)-CCK-7 (1 nmol/kg) had satiety effect after ip administration. Dose-response studies indicated the following rank order of potency: Suc-CCK-7 > or = Suc-(Thr28, Leu29, MePhe33)-CCK-7 > or = CCK-8 > or = (Nle28,31)-CCK-8 >> desulfated CCK-8 = CCK-4 = 0 in the case of ip administration and Suc-(Thr28, Leu29, MePhe33)-CCK-7 >> Suc-CCK-7 > or = CCK-8 > or = (Nle28,31)-CCK-8 >> desulfated CCK-8 = CCK-4 = 0 in the case of icv administration. The selective CCK-A receptor antagonist MK-329 reversed the inhibitory effect of the centrally as well as peripherally administered CCK-8, or of Suc-(Thr28, Leu29, MePhe33)-CCK-7, whereas the selective CCK-B receptor antagonist L-365260 did not. The icv administered CCK-8 did not appear in the peripheral circulation. These findings suggest the participation of CCK-A receptors in the brain in mediating the satiety effect of CCK and the difference in CCK-A receptors in the brain and peripheral tissues. PMID- 8214138 TI - Skeletal muscle Ca2+ flux and catabolic response during sepsis. AB - Membrane Ca2+ flux and net protein catabolism were studied in the skeletal muscle during experimental sepsis. Sterilized rat fecal pellets with (septic) or without (sterile) gram-negative bacteria, Escherichia coli [10(2) colony-forming units (cfu)] and Bacteroides fragilis (2 x 10(3) cfu), were implanted into the abdomens of male Sprague-Dawley rats (110-120 g). Septic and sterile rats were febrile and hyperlactacidemic on day 1 postimplantation. These responses subsided by day 2 in sterile but not septic rats. Initial Ca2+ flux, estimated from measurements of 45Ca uptake by soleus muscles in vitro, was elevated on day 1 in both sterile and septic rats and on day 2 and 3 in septic rats only. The septic rat soleus muscle showed a significantly increased net protein catabolic response (measured as tyrosine release by soleus muscle, in vitro) over that found in muscles of sterile rats on day 1-3 postimplantation. The increase in Ca2+ flux in septic (day 1-3 postimplantation) and sterile (day 1 only) rats was abolished when the rats were treated with the calcium channel blocker diltiazem. In unoperated control rat soleus muscles the Ca2+ ionophore, ionomycin, concomitantly caused an increase in Ca2+ flux and net protein catabolism. Overall, the present study suggested that altered cellular Ca2+ regulation plays a role in the net protein catabolic response in the skeletal muscle during sepsis. PMID- 8214139 TI - Ventilatory CO2-induced optical activity changes of cat ventral medullary surface. AB - We examined neuronal activation of the ventral medullary surface (VMS) during hypercapnic challenges using optical recording procedures. With a coherent imaging probe, we assessed reflected 700-nm light from 18 VMS sites in 11 spontaneously breathing adult cats and from the suprasylvian cortex in two cats. Video frames were acquired during a baseline period, hypercapnic (3, 5, and 10% CO2 in O2) exposure, and recovery. Hypercapnic exposure elicited overall reflectance changes in all VMS sites, but no changes in the suprasylvian cortex. Light reflectance changes, suggesting altered neuronal activity, were reproducible, occurred as early as 30 s after CO2 exposure, and were dose dependent. The changes persisted approximately 20-25 min beyond the stimulus, but respiratory responses consistently recovered within 2-3 min. Although more rostral VMS sites tended to be associated with decreased activity and caudal regions with increased excitation, no uniform topographical organization was apparent across animals. The variability in VMS optical reflectance patterns across animals during CO2 stimulation may reflect the heterogeneous topographical distribution of responsive neurons in the structure. PMID- 8214140 TI - Role of hypothalamic interleukin-6 and tumor necrosis factor-alpha in LPS fever in rat. AB - The purpose of this study was to determine, using push-pull perfusion, the levels of interleukin (IL)-1-like, IL-6-like, and tumor necrosis factor-alpha (TNF)-like activity in the anterior hypothalamus during lipopolysaccharide (LPS)-induced fever in rats. Additionally, slow anterior hypothalamic infusions of human recombinant IL-6 (hrIL-6) or TNF (hrTNF) for several hours were performed to determine possible febrile effects of these two cytokines. Artificial cerebrospinal fluid (aCSF) was infused as a control. Samples of cerebrospinal fluid were collected 60 min before and 60, 180, 300, and 420 min after the intraperitoneal injection of LPS. A control group was injected intraperitoneally with saline. The core temperature (measured by biotelemetry) of LPS-injected rats was significantly higher (P < 0.05) than the temperature of the rats injected with saline at 180, 300, and 420 min after the injection. The average postinjection IL-6 levels were significantly higher (P < 0.05) in the LPS injected group. TNF was significantly higher (P < 0.05) than the baseline only at 180 min. There were no changes in levels of IL-1-like activity. Infusion of hrIL 6 at a level similar to the peak IL-6 level measured during LPS-induced fever resulted in a slowly developing and long-lasting increase in core temperature. Infusion of hrTNF at a level corresponding to the peak TNF level measured during LPS-induced fever did not induce a significant increase in core temperature. These results support the hypothesis that elevated hypothalamic concentrations of IL-6 are involved in the induction of fever elicited by peripheral (intraperitoneal) injection of LPS. PMID- 8214141 TI - Nitric oxide and superoxide in cultured cells: limited production and influence on DNA synthesis. AB - The ability of superoxide (O2-) and NO to influence DNA synthesis, as estimated by [3H]thymidine incorporation in logarithmically growing cells, was evaluated in three human cell types: embryonic lung fibroblasts, skin fibroblasts, and mesangial cells. Nontoxic rates of O2- generation (0.2 nM/min-0.2 microM/min) only slightly stimulated DNA synthesis in mesangial cells (10-13% increase) and did not affect fibroblast DNA synthesis. Nontoxic rates of NO generation (0.1-10 microM/min) also had only limited effects, inhibiting DNA synthesis in lung and skin fibroblasts slightly (10-20% decrease) but not affecting mesangial cells. In all three cell types, neither O2- nor NO was generated at high enough endogenous rates to support an autocrinic regulation of DNA synthesis. This and other lines of evidence indicate that a reaction between O2- and NO is unlikely to account for their opposing effects on DNA synthesis. PMID- 8214142 TI - Role of V1 receptors in the action of vasopressin on the baroreflex control of heart rate. AB - Arginine vasopressin (AVP) elicits a larger decrease in heart rate for a given increase in arterial pressure than do other vasoconstrictors, but there is disagreement as to whether this results from an increase in baroreflex gain or a resetting of the baroreflex to a lower blood pressure. It is also unclear which type of vasopressin receptor mediates the action of vasopressin on the baroreflex. In the present study, the effects of vasopressin, selective vasopressin V1 and V2 receptor agonists, oxytocin, and a vasopressin V1 receptor antagonist on the baroreflex control of heart rate were investigated in conscious, chronically prepared rabbits. Baroreflex curves were generated with intravenous infusions of phenylephrine and nitroprusside and analyzed using a four-parameter logistic model. Intravenous infusion of vasopressin at 5 ng.kg 1.min-1 increased mean arterial pressure by 9 mmHg and decreased heart rate by 31 beats/min. The arterial pressure at the midrange of the baroreflex curve (BP50) decreased from 75.9 +/- 4.8 to 57.6 +/- 1.7 mmHg (P < 0.01), indicating a shift of the baroreflex curve to a lower pressure, but the gain did not change significantly. The actions of vasopressin on blood pressure, heart rate, and BP50 were completely blocked by pretreatment with d(CH2)5[Tyr(Me)2]AVP, a selective V1 receptor antagonist. Infusion of [Phe2,Ile3,Orn8]AVP, a selective V1 receptor agonist, produced cardiovascular effects similar to those of vasopressin and decreased the BP50 of the baroreflex from 73.0 +/- 2.2 to 63.8 +/- 2.2 mmHg (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214143 TI - A comparison of inhibitory effects of neuropeptide Y on rat urinary bladder, urethra, and vas deferens. AB - The effects of human and porcine neuropeptide Y (NPY) on electrically induced contractions of smooth muscle strips from rat urinary bladder, urethra, and vas deferens were investigated. NPY (10 nM-10 microM) inhibited to the contractile response in all preparations. The magnitude of inhibition by NPY was dependent on frequency of stimulation in each organ, the inhibition being in general much greater (80-100%) at low frequencies (2-5 Hz) than at high frequencies (30-40% at 10-100 Hz). The vas deferens and urethra exhibited nearly maximal inhibition (90 100%) over a broader range of stimulus frequencies (1-20 Hz), while the bladder exhibited a more prominent inhibition at frequencies of stimulation below 2 Hz. When tested at 20 Hz stimulation the urethra and vas deferens were very sensitive (70-90% inhibition) to both types of NPY, whereas bladder strips were much less sensitive to NPY and the effect differed with the two types of NPY (16% inhibition with human NPY and 39% inhibition with porcine NPY). In the urinary bladder, NPY inhibited the cholinergic component of the contractile response, while in the urethra adrenergic transmission was primarily affected. These studies suggest that NPY, which is present in both cholinergic and adrenergic neurons in the pelvic ganglia, may have an important role in the neural control of the lower urinary tract by participating in autoinhibition at autonomic nerve terminals as well as in the heterosynaptic interactions between the cholinergic and adrenergic pathways. PMID- 8214144 TI - Insulin-mediated glycogen synthase activity in muscle of spontaneously insulin resistant and diabetic rhesus monkeys. AB - Altered insulin action on glycogen synthase activity has been well recognized in non-insulin-dependent diabetes, and some prior evidence has suggested this alteration may be one of the earliest disturbances preceding the development of diabetes. The present study, using the spontaneously insulin-resistant and diabetic rhesus monkey, examined insulin's effect on glycogen synthase at the earliest point of identification of developing diabetes. The normal monkeys (n = 11) had a greater insulin-mediated change in glycogen synthase-independent activity compared with the hyperinsulinemic (n = 8) (P < 0.05) and diabetic (n = 8) (P < 0.01) monkeys. Compared with normal monkeys, the diabetic monkeys had lower basal and insulin-stimulated total glycogen synthase activity (P < 0.05). Monkeys with normal beta-cell responsiveness to intravenous glucose had greater insulin-mediated change in glycogen synthase fractional velocity compared with those with exaggerated (P < 0.01) or absent beta-cell responses to glucose (P < 0.05). We conclude that an alteration in insulin action on glycogen synthase is present as early as beta-cell hyperresponsiveness, one of the earliest detected abnormalities in the progression toward diabetes. PMID- 8214145 TI - Tamoxifen antagonizes the effects of estradiol on energy balance and estrous behavior in Syrian hamsters. AB - Ovariectomized Syrian hamsters were treated with estradiol benzoate (5 micrograms/day for 4 wk), tamoxifen (500 micrograms/day), an antiestrogen that competes with estradiol for central and peripheral estrogen receptors, or both estradiol benzoate and tamoxifen. As expected, estradiol treatment caused significant decreases in body weight and fat content without affecting food intake. Given alone, tamoxifen had no effect on body weight or composition, but when given concurrently, tamoxifen significantly attenuated the effects of estradiol. These results stand in contrast to findings in rats where nonsteroidal antiestrogens, including tamoxifen, mimic the effects of estradiol on body weight and energy metabolism and are completely devoid of any antiestrogenic actions. As in rats, tamoxifen was a potent inhibitor of estrous behavior, whether induced with estradiol alone or with sequential treatment with estradiol and progesterone. Again, as in rats, tamoxifen acted as an antagonist and a weak estrogen agonist on uterine weight. These findings support the notion that the relative agonistic and antagonistic actions of tamoxifen, and other antiestrogens, vary with species and with the estrogen-sensitive endpoint being investigated. PMID- 8214146 TI - Energy balance in pregnant hamsters: a role for voluntary exercise? AB - During pregnancy or after experimental manipulations of ovarian hormone levels, Syrian hamsters exhibit changes in energy balance and body fat content without modifying their food intake. The present experiments determined whether fluctuations in voluntary exercise play a role in these changes in energy balance, as they appear to do in other species. As expected, pregnant hamsters maintained a constant level of food intake and lost approximately 40% of their body fat. These animals did not show the abrupt decrease in activity after mating that is seen in rats. Instead, they maintained their high, premating level of running wheel activity until the last 3 days of pregnancy. Similarly, ovariectomy and replacement therapy with estradiol or estradiol+progesterone caused substantial changes in energy balance in the absence of significant changes in food intake or running wheel activity. These findings indicate that, unlike rats, Syrian hamsters do not exhibit substantial changes in voluntary exercise during pregnancy or in response to manipulations of ovarian steroid levels. Therefore, neither changes in food intake nor in voluntary exercise play any important role in the pregnancy- or steroid-induced changes in energy balance in Syrian hamsters. PMID- 8214147 TI - Endothelium-derived relaxing factor responses in Doca-salt hypertensive rats. AB - This study examined the contribution of endothelium-derived relaxing factor (EDRF) to the susceptibility of uninephrectomized rats to deoxycorticosterone acetate (DOCA)-salt hypertension. N omega-nitro-L-arginine, a probe for EDRF, produced smaller increases (P < 0.001) in mean arterial pressures in anesthetized hypertensive DOCA-salt rats than in sham rats. Acute L-arginine administration (300 mg/kg body wt i.v.) failed to reduce pressure in anesthetized DOCA-salt rats. Chronic oral and intraperitoneal L-arginine did not lower pressure in conscious DOCA-salt rats with established hypertension, nor did it prevent hypertension when begun in prehypertensive DOCA-salt rats. Preconstricted aortic rings from DOCA-salt rats had attenuated relaxation to acetylcholine compared with sham rats. Rings L-arginine-treated DOCA-salt rats had responses similar to DOCA-salt rats. Relaxation to nitroprusside was not different between any rat group. Thus EDRF is attenuated in DOCA-salt hypertension. However, unlike several other hypertensive models, the blunted EDRF response cannot be overcome by provision of L-arginine. These data suggest synthesis or release of EDRF may be noncompetitively inhibited in DOCA-salt hypertension. PMID- 8214148 TI - Cardiovascular actions of dogfish urotensin II in the dogfish Scyliorhinus canicula. AB - Bolus injections of synthetic dogfish urotensin II (0.1-1.0 nmol) into the celiac artery of the conscious dogfish Scyliorhinus canicula (n = 8) resulted in sustained and dose-dependent increases in arterial blood pressure and pulse pressure. A maximum rise in mean arterial pressure of 10.5 +/- 1.2 mmHg (equivalent to 38.6 +/- 4.2% over mean basal values) and a maximum increase in pulse pressure of 3.9 +/- 0.8 mmHg was elicited by injection of 0.5 nmol of peptide. In comparison, a bolus injection of epinephrine (5 nmol) elicited a rise of 24.8 +/- 3.3% in mean arterial pressure. Bolus injection of 0.5 nmol synthetic goby (Gillichthys mirabilis) urotensin II under the same conditions did not elicit a significant hypertensive response. When dogfish urotensin II (0.5 nmol) was administered 3 min after an intra-arterial injection of phentolamine, the rise in arterial blood pressure was completely abolished. Dogfish urotensin II produced a dose-dependent contraction (pD2 = 6.58 +/- 0.07; n = 8) of isolated rings of vascular muscle prepared from the first afferent branchial artery of the dogfish. A maximum contractile force of 1.3 mN was produced by 10(-5) M peptide. The urotensin II-induced contraction of the vascular rings was unaffected by pretreatment with tetrodotoxin (1 microM) or indomethacin (14 microM). It is concluded that urotensin II has potent hypertensive activity in the dogfish that is mediated, at least in part, through release of catecholamines, but the sustained nature of the pressor response suggests that the peptide may have a direct action on the heart. PMID- 8214149 TI - Norepinephrine- and insulin-resistant glucose transport in brown adipocytes from diabetic SHR/N-cp rats. AB - The effects of norepinephrine and insulin on glucose transport were investigated in brown adipocytes isolated from obese nondiabetic Lister and Albany (LA/N-cp strain) rats (O-LA), obese diabetic spontaneously hypertensive (SHR/N-cp strain) rats (O-SHR), and from their lean (L) controls to test whether the decreased calorigenic response to norepinephrine of O-SHR adipocytes was specifically associated with alterations in glucose metabolism. Norepinephrine and insulin independently stimulated glucose transport in L-LA, O-LA, and L-SHR brown adipocytes, but their stimulatory effects were markedly reduced in O-SHR cells. Both insulin responsiveness and the total number of insulin receptors were significantly decreased in O-SHR adipocytes but not in O-LA cells. The number of high-affinity beta 1/beta 2-adrenoceptors was significantly increased (+70%) in O LA adipocytes but was similar in L-SHR and O-SHR cells. These results indicate that 1) major metabolic defects are present in brown adipose tissue (BAT) of O SHR but not of O-LA, although these two strains are homozygous for the cp allele, 2) postreceptor defects are predominantly involved in O-SHR adipocyte refractoriness to norepinephrine, and 3) a reduced mitochondrial content may represent the principal metabolic alteration explaining the decreased effects of norepinephrine on both thermogenesis and glucose transport. It is postulated that the marked insulin resistance of O-SHR leads to a decreased mitochondriogenesis in BAT, resulting in a diminished tissue thermogenic capacity and reduced glucose metabolism, thereby contributing to obesity and diabetes. PMID- 8214150 TI - Atrial natriuretic factor counteracts sodium-retaining actions of insulin in normal men. AB - It has been hypothesized that hyperinsulinemia is causally related to hypertension by its effect on renal sodium transport. To examine the relationship between the sodium-retaining actions of insulin and atrial natriuretic factor (ANF), 16 healthy subjects were studied on three occasions, approximately 1 wk apart, using standard clearance techniques to evaluate responses during the acute administration of insulin, low-dose ANF, or both. In study 1, the euglycemic clamp was used to increase plasma insulin 10-fold to an average of 320 +/- 14 (SE) pM. This maneuver produced an immediate and persistent fall in sodium excretion from 0.315 +/- 0.02 to 0.207 +/- 0.02 mmol/min (P < 0.001) independent of change in renal hemodynamics, lithium clearance, and catecholamines. The decline in sodium excretion was associated with a marked increase in fractional distal sodium reabsorption. Systolic and diastolic pressure did not change significantly. In study 2, low-dose ANF (0.3 pmol.kg-1.min-1) designed to raise plasma levels to twice baseline was administered simultaneously in a repeat of study 1. This maneuver abolished insulin-mediated sodium reabsorption. In study 3, low-dose ANF infusion alone produced no changes in tubular handling of sodium. Our findings indicate that insulin at levels found in hyperinsulinemic states caused sodium retention and that physiological increases in plasma ANF concentration abolished the sodium-retaining action of insulin. Our findings suggest that if hypertension is causally related to hyperinsulinemia, mechanisms besides renal sodium retention are responsible for the hypertensive properties of insulin. PMID- 8214151 TI - Role of arteria baroreceptor input on thirst and urinary responses to intracerebroventricular angiotensin II. AB - Intracerebroventricular (icv) infusion of angiotensin II (ANG II) in rats elicits greater water intake under hypotensive, compared with normotensive, conditions. The present experiments used sinoaortic baroreceptor-denervated (SAD) rats and sham-operated rats to examine if the modulatory effects of arterial blood pressure on water intake in response to icv ANG II are mediated by arterial baroreceptors. Mean arterial blood pressure (MAP) was raised or lowered by intravenous (i.v.) infusions of phenylephrine (1 or 10 micrograms.kg-1 x min-1) or minoxidil (25 micrograms.kg-1 x min-1), respectively. The angiotensin converting enzyme inhibitor captopril (0.33 mg/min) was infused i.v. to prevent the endogenous formation of ANG II during testing. Urinary excretion of water and solutes was measured throughout. Water intake elicited by icv ANG II was inversely related to changes in MAP. Specifically, rats drank more water in response to icv ANG II when MAP was reduced by minoxidil but drank less water when MAP was elevated by phenylephrine. The influence of changing MAP on the icv ANG II-induced drinking responses was not affected by SAD. These results suggest that the modulatory effects of arterial blood pressure on icv ANG II-induced drinking can occur in the absence of sinoaortic baroreceptor input. PMID- 8214152 TI - Autonomic modulation of ovine fetal responses to atrial natriuretic factor infusion. AB - The aim of this study was to determine whether the autonomic nervous system modulates the cardiovascular, endocrine, and/or urinary responses to atrial natriuretic factor (ANF) infusion in the fetus. We infused ANF intravenously for 30 min into chronically catheterized, late-gestation sheep fetuses with autonomic blockade and compared the responses to those in autonomically intact fetuses. During the infusions, plasma ANF concentration increased similarly in the blocked and intact fetuses. Arterial pressure decreased by 2 mmHg in both groups, but the decrease occurred earlier in the blocked fetuses. Heart rate was significantly decreased by an average of 15 beats/min in the blocked compared with the intact fetuses. Plasma protein concentration decreased in the blocked fetuses compared with a rise in the intact fetuses. In the blocked fetuses, the restoration of blood volume to normal during the postinfusion period occurred earlier. In the blocked animals, low doses of ANF produced a diuresis, whereas high doses did not increase urine flow; the opposite responses occurred in the intact group. Plasma arginine vasopressin (AVP) concentration increased during the infusion only in the blocked animals. The fetal venous pressure, plasma renin activity, and norepinephrine responses were similar in both groups. These data suggest that the autonomic nervous system may play a role in modulating the fetal arterial pressure, heart rate, blood volume, plasma protein concentration, AVP, and urine flow responses to ANF. Thus the autonomic nervous system appears to significantly modulate multiple responses to ANF in the late-gestation ovine fetus. PMID- 8214153 TI - Abdominal vagotomy dissociates the anorectic mechanisms for peripheral serotonin and cholecystokinin. AB - These studies compared the effects of total abdominal vagotomy (VGX) on ingestive actions produced by peripheral serotonergic and cholecystokinergic (CCKergic) stimulation in rats. Subcutaneous injection of 0.01-0.16 mumol/kg of the serotonin (5-HT) analogue 5-carboxamidotryptamine (5-CT) dose-dependently reduced mash intake equally in VGX rats and their laparotomized (LAP) controls but concurrently stimulated drinking only in the controls. The sulfated octapeptide of cholecystokinin (CCK-8, 4.0 nmol/kg ip) also reduced food intake only in the controls. In a second set of rats, vagotomy did not alter anorexia after intraperitoneal administration of either 2.0 or 8.0 mumol/kg of 5-HT or of 0.03 mumol/kg of 5-CT but abolished anorexia after a large dose of CCK-8 (8.0 nmol/kg). The completeness of vagotomy was verified histologically by immunohistochemical staining of the vagal bundles for the high molecular weight form of neurofilament-H protein. We report for the first time that 5-CT produces anorexia by a vagally independent mechanism. In contrast, 5-CT stimulates drinking by a pathway that does involve vagal function. Finally, we confirm the prediction that vagotomy dissociates the neural mechanisms for the anorectic action of peripheral 5-HTergic and CCKergic stimulation. PMID- 8214154 TI - Gastric vagus mediates immobilization-induced hypocalcemia in rats. AB - The involvement of the parasympathetic nervous system in the etiology of stress induced hypocalcemia was investigated in the rat. Atropine methyl bromide (0.1 and 0.6 mg/kg ip) given 20 min before immobilization (IMB) was observed to suppress the induction of hypocalcemia in a dose-dependent manner. A vagotomy of the bilateral cervical trunks also abolished the IMB-induced hypocalcemia. A vagotomy on either the thyroid/parathyroid branches or the celiac branches had no effect on the IMB-induced hypocalcemia, but a vagotomy on the gastric branches completely abolished it. Pretreatment with either secretin (2 and 6 micrograms/kg ip), an inhibitor of gastrin release, or cimetidine (5 and 10 mg/kg ip), a histamine H2-receptor antagonist, diminished the IMB-induced hypocalcemia. The concentration of serum gastrin increased significantly during IMB. It is thus concluded that the decreased levels of plasma calcium caused by IMB are due to the activation of the vagus innervating the stomach. Gastrin and histamine are also involved as a consequence of the activation of the vagus. PMID- 8214155 TI - Anti-TNF-alpha antibodies normalized body temperature and enhanced food intake in tumor-bearing rats. AB - Anorectic weight-losing Fischer 344 rats bearing a methylcholanthrene-induced sarcoma received intraperitoneal injections of rabbit antiserum raised against murine tumor necrosis factor (TNF)-alpha at 14, 18, and 24 days after tumor induction. Treatment of tumor-bearing rats with TNF antiserum partially reversed the tumor-induced reduction in food intake compared with tumor-bearing rats that received control serum. In the same tumor-bearing animals, treatment with TNF antiserum delayed the onset and significantly reduced the decline in mean 12-h daytime and nighttime intra-abdominal temperatures on days 18-25. However, anti TNF antibody treatment did not alter the declines in carcass weight or motor activity measured from day of tumor induction until death or reduce the tumor burden at death. We conclude that an endogenous TNF response may be one of the factors involved in the development of cancer anorexia and that this cytokine has temperature-lowering properties. PMID- 8214156 TI - Blockade of type A, but not type B, CCK receptors postpones satiety in rhesus monkeys. AB - The exogenous administration of the brain/gut peptide cholecystokinin (CCK) inhibits food intake in a variety of species, including subhuman primates and humans. To determine the role of endogenously released CCK in the control of food intake in rhesus monkeys, we examined the ability of the selective type A and type B CCK antagonists devazepide and L-365260 to affect total daily food intake and various meal patterns. Various doses of the antagonists were administered intragastrically 30 min before a daily 4-h feeding period. One-gram food pellets were delivered in response to lever pulls, and intake was computer monitored. Intragastric administration of the type A CCK receptor antagonist devazepide (10 320 micrograms/kg) significantly increased food intake in a dose-related fashion. The threshold for increasing intake was 32 micrograms/kg, and a maximal effect was obtained at a dose of 100 micrograms/kg that increased total 4-h food intake by 47%. The effect of devazepide on food intake was mediated by significant increases in the size and duration of the initial meal, lengthening of the subsequent intermeal interval, and a decrease in the satiety ratio (intermeal interval/1st meal size). In contrast, intragastric administration of the type B CCK receptor antagonist L-365260 (3.2-320 micrograms/kg) did not significantly affect total food intake or any of the meal parameters. These data demonstrate that endogenously released CCK acting through type A CCK receptors plays a role in regulating food intake in rhesus monkeys. PMID- 8214157 TI - Cardiovascular consequences of microinjection of vasopressin and angiotensin II in the area postrema. AB - Microinjection of angiotensin II (ANG II) into the area postrema (AP) of urethan anesthetized male Sprague-Dawley rats elicited statistically significant increases in mean arterial blood pressure at doses ranging from 10 pg to 500 ng (10 pg, mean +/- SE, 10.8 +/- 1.1 mmHg, P < 0.001; 250 ng, 15.2 +/- 2.6 mmHg, P < 0.001). Heart rate was also significantly increased at doses > 10 pg, although these increases were not dose dependent. Systemic administration of losartan (Dup 753), an AT1 antagonist, was able to significantly reduce the pressor response to 250 ng ANG (post-losartan: 81.9 +/- 9.5% reduction in blood pressure response, P < 0.0001), whereas PD123319, an AT2 antagonist, was without significant effect (P > 0.1). Microinjection of vasopressin (VP) (10 pg-500 ng) into the AP also resulted in statistically significant increases in blood pressure at doses ranging from 10 to 100 pg (10 pg, 7.0 +/- 1.5 mmHg, P < 0.05) and 100-500 ng (250 ng, 12.2 +/- 1.8 mmHg, P < 0.0001). Small but significant changes in heart rate were observed only at 100 pg and 100 ng. Systemic administration of a V1 antagonist significantly attenuated the increases in blood pressure in response to 50, 100, and 250 ng VP (250 ng, post-V1 antagonist: 66.4 +/- 8.6% reduction in blood pressure response, P < 0.001), whereas [desamino,D-Arg8]vasopressin (DDAVP), a V2 agonist, had a depressor effect when microinjected directly into the AP (250 ng, -9.9 +/- 1.6 mmHg, P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214158 TI - Plasma catecholamine and corticosterone and their in vitro effects on lizard skeletal muscle lactate metabolism. AB - Lizard skeletal muscles utilize primarily lactate as a gluconeogenic substrate for glycogen replenishment following exercise. To understand the influence of selected hormones on this process, we measured changes in plasma catecholamines and corticosterone resulting from exercise in the lizard Dipsosaurus dorsalis and then investigated the physiological effects of those hormones on skeletal muscle lactate and glucose metabolism in vitro. Plasma epinephrine (Epi), norepinephrine, and corticosterone (Cort) increased 5.8, 10.2, and 2.2 times, respectively, after 5 min of exhaustive exercise. Epi and Cort levels remained elevated after 2 h of recovery. Skeletal muscle fiber bundles isolated from the red and white regions of the iliofibularis muscle were incubated 2 h at 40 degrees C in the presence of postexercise concentrations of [14C]lactate (15 mM) and glucose (8.5 mM) in the presence and absence of Epi or Cort. Red muscle oxidized both substrates at 2-3 times the rate of white muscle, and both red and white fibers oxidized lactate at 5-10 times the rate of glucose oxidation. Epi had a stimulatory effect on lactate oxidation by white muscle. Lactate incorporation into glycogen proceeded at 2-3 times the rate of glucose incorporation in both muscle types, with rates in red muscle again 2-3 times that for white muscle. Epi stimulated lactate carbon incorporation into glycogen by 50 140% in both red and white muscle but had no effect on glucose incorporation into glycogen in either tissue. We interpret these data as evidence that epinephrine stimulates lactate removal by skeletal muscle. Cort had no effect on lactate metabolism in either muscle type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214159 TI - Increased uteroplacental production of prostaglandin E2 during ethanol infusion. AB - Experiments were conducted in 14 pregnant sheep to determine the effect of a 1-h maternal infusion of ethanol (1 g/kg maternal body wt) on placental efflux of prostaglandin E2 (PGE2), umbilical blood flow (Qum), and carbohydrate metabolism at 123-130 days gestation. This ethanol dosage regimen produced peak ethanol concentrations in fetal and maternal blood in the range of 1.48-1.64 mg/ml at the end of the infusion. Umbilical venous and fetal arterial PGE2 concentrations increased (P < 0.05) from 315 +/- 47 and 202 +/- 25 pg/ml to 740 +/- 172 and 489 +/- 67 pg/ml, respectively, at the end of the infusion. Placental secretion of PGE2 into the fetal circulation increased by 45% (P < 0.05). Uterine venous and maternal arterial PGE2 concentration increased (P < 0.05) from 370 +/- 27 and 262 +/- 28 pg/ml to 705 +/- 51 and 487 +/- 69 pg/ml, respectively. Fetal and maternal blood glucose concentration decreased (P < 0.05) from 0.98 +/- 0.11 and 2.88 +/- 0.25 mmol/l to 0.81 +/- 0.21 and 2.44 +/- 0.16 mmol/l, respectively. Fetal and maternal blood lactate concentration increased (P < 0.05) from 1.40 +/- 0.11 and 0.68 +/- 0.07 mmol/l to 1.67 +/- 0.14 and 1.82 +/- 0.16 mmol/l, respectively. Qum, fetal heart rate, fetal blood pressure, and fetal and maternal blood gases were unchanged by the ethanol infusion. These results support the hypothesis that the placenta is the major source of the elevated fetal and maternal plasma PGE2 concentrations produced in pregnant sheep by maternal ethanol administration. PMID- 8214160 TI - Antioxidant defenses in the tolerance of freezing and anoxia by garter snakes. AB - The garter snake Thamnophis sirtalis parietalis can readily tolerate several hours of freezing or anoxia exposure. Both stresses halt oxygen availability to tissues and to endure these stresses snakes must cope with potential oxidative stress arising as a result of the ischemic/anoxic condition followed by reperfusion of aerated blood during recovery. To determine whether antioxidant defenses are important for freezing and anoxia survival, we monitored the activities of antioxidant enzymes and the levels of glutathione (GSH and GSSG) during freezing (5 h at -2.5 degrees C) and anoxia (10 h under N2 gas at 5 degrees C) exposures in three organs (muscle, liver, and lung) of snakes. Freezing resulted in a significant rise in the activity of muscle and lung catalase (by 183 and 63%) and in muscle glutathione peroxidase (52%). Anoxia enhanced muscle and liver superoxide dismutase activities (by 59 and 118%) and also caused a 57% increase in muscle GSH levels. The increase in muscle GSH concentration in anoxia (from 0.45 to 0.71 mM) could also stimulate muscle glutathione peroxidase activity in vivo by 1.5-fold because of its low affinity for GSH (Km = 11 mM). The ratio of GSSG/GSH was not affected by experimental state in any tissue, suggesting that oxidative stress did not occur during the freezing or anoxic exposure. Rather, H2O2- and O2(-)-detoxification systems may be activated in preparation for possible oxygen free radical overgeneration during thawing or reoxygenation. Antioxidant defenses appear to be part of the adaptive machinery for reptilian tolerance of freezing and anoxia. PMID- 8214161 TI - Kinetics of systemic and intrahypothalamic IL-6 and tumor necrosis factor during endotoxin fever in guinea pigs. AB - The time course of activity of interleukin-6 (IL-6) and tumor necrosis factor (TNF) was measured in blood plasma and hypothalamic push-pull perfusates during the febrile response to intramuscular injection of bacterial endotoxin (Escherichia coli, 20 micrograms/kg) in 24 guinea pigs. Injection of endotoxin caused a dramatic increase of IL-6 activity in plasma. The logarithmic values of plasma IL-6 activities showed a linear correlation to the febrile change in body temperature (r = 0.898) during the whole time course of fever. IL-6 activity in hypothalamic perfusates increased 12-fold in the first hour after pyrogen application and declined slowly despite the further increase in body temperature. Hypothalamic IL-6 activity did not correlate with the febrile increase in body temperature (r = -0.048). TNF activity in plasma, not detectable before pyrogen application, had its peak in the first hour after endotoxin injection and rapidly declined to 15-20% of the peak activity within the next 2 h and to an undetectable value 5 h after injection. In the hypothalamus TNF was not detectable before endotoxin injection, but it could be monitored in most animals after pyrogen application without a clear correlation to the fever response. These results taken together indicate that endotoxin fever represents a physiological situation in which production and release of cytokines in the peripheral immune system and in the hypothalamus are regulated and stimulated in independent patterns. PMID- 8214162 TI - Asymmetrical transfer of inert hydrophilic solutes across rat placenta. AB - Transfer of [14C]mannitol, 51Cr-labeled EDTA, and [14C]-inulin from mother to fetus and from fetus to mother was measured in rats under pentobarbital anesthesia. The clearance of the three substances from the mother to fetus (Kmf) was 2.69 +/- 0.38, 1.93 +/- 0.73, and 0.47 +/- 0.14 microliter/min (means +/- SE), respectively, and the clearance from fetus to mother (Kfm) was 5.97, 6.66, and 4.95 microliters/min, respectively (the SE could not be estimated). Kfm appears to be consistently higher than Kmf by an almost constant value of approximately 4 microliters/min. To explain this a hypothesis was proposed according to which volume flow circulates across the placenta. Solute-free water is driven transcellularly across the placental barrier from the maternal to the fetal side by a difference of osmotic pressure created by active transport of some solutes (mainly Na+) to the fetus. Water together with all solutes dissolved returns from fetus to mother by filtration through wide extracellular channels in the placenta down a hydrostatic pressure gradient. PMID- 8214163 TI - Postnatal development of uncoupling protein, uncoupling protein mRNA, and GLUT4 in adipose tissues of goats. AB - Adipose tissues have been characterized in newborn goats on the basis of the presence of the 32,000-M(r) mitochondrial uncoupling protein (UCP) diagnostic of brown fat, and early postnatal developmental changes have been determined. Both internal (perirenal, pericardial, and omental) and subcutaneous (hindlimb and neck regions) adipose tissues in newborn goats contained UCP and are therefore brown fat. The insulin-sensitive glucose transporter, GLUT4, was also present in adipose tissues of newborn goats, implying a potential for insulin-stimulated glucose uptake at birth. UCP was still evident in the perirenal fat of goats at 3 wk of age, but the mitochondrial concentration was only 4%, and the amount per cell a mere 0.2%, of that in the newborn. UCP was not detectable, however, in either the omental or subcutaneous adipose tissue at 3 wk of age and had disappeared from the subcutaneous fat before 2 wk. In contrast to UCP, GLUT4 remained throughout the initial 3 wk of postnatal life. The mRNA for UCP was detected in perirenal adipose tissue of newborn goats, indicating that the gene coding for the protein is being expressed at around birth. UCP mRNA was not, however, detectable in the other fat depots; nor was it evident in the perirenal adipose tissue at > or = 2.5 days of age. It is concluded that the adipose tissues of newborn goats (both internal and subcutaneous) represent brown fat and that there is a rapid transition toward white fat over the first weeks of life. This transition occurs at different rates in different depots but is not markedly faster in goats than in other ruminants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214164 TI - Involvement of central vs. peripheral mechanisms in mediating sympathoadrenal activation in endotoxic rats. AB - The contribution of central vs. peripheral mechanisms in mediating increases in plasma norepinephrine (NE) and epinephrine (Epi) during endotoxicosis were studied. Plasma catecholamine responses after endotoxin were assessed in conscious animals and in animals without central regulatory mechanisms (pithed rats). In conscious rats, endotoxin (1.5 mg/kg i.v.) induced a marked elevation in plasma NE after 90 min (3-fold), but elevations were not seen in pithed rats. Endotoxin also induced a profound increase (12- to 13-fold) in plasma Epi in conscious rats, but increases were less (2- to 3-fold) and delayed in pithed rats. These results suggest that central mechanisms are essential in plasma NE response to endotoxic challenge, whereas plasma Epi response involves both central and peripheral mechanisms, with the former being dominant. In conscious adrenal-denervated animals, plasma Epi was not elevated until 90 min postendotoxin. This delayed Epi elevation was approximately one-third of the maximal response observed in conscious adrenal-intact rats. In pithed adrenal denervated rats, plasma Epi at 90 min postendotoxin was also increased to a level comparable to that in pithed adrenal-intact rats. These results imply that a significant fraction of peripheral release of Epi with endotoxicosis is nonneurogenic. PMID- 8214165 TI - Brain lactate and pH dissociation in edema: 1H- and 31P-NMR in collagenase induced hemorrhage in rats. AB - Brain edema has been shown to increase brain lactate, but the effect on pH is unclear. We used in vivo nuclear magnetic resonance (NMR) spectroscopy to measure lactate and pH in a region of brain edema. Ninety-five anesthetized rats underwent proton and 31P-NMR spectroscopy with a 7-T 89-mm vertical bore spectrometer, using a surface coil over the edematous regions and distant from a hemorrhage produced by the injection of bacterial collagenase. Brain water content was measured from multiple regions after the NMR measurements in all rats. Lactate was significantly increased 4 h after the hemorrhage and remained elevated for 48 h, but brain pH was unaffected. The increase in lactate correlated (P < 0.01) with the increase in water content in the measured region. We conclude that lactate and pH are dissociated in a region of primarily vasogenic edema. PMID- 8214166 TI - Intestinal lymphatic pressure increases during intravenous infusions in awake sheep. AB - Intravenous fluid infusions cause increased venous pressure and increased lymph flow throughout the body. Together the increased lymph flow and increased venous pressure (the outflow pressure to the lymphatic system) should increase the pressure within the postnodal intestinal lymphatics. To test this, we measured the pressure in postnodal intestinal lymphatics and the neck vein pressure in five awake sheep. At baseline, the neck vein pressure was 1.2 +/- 1.5 (SD) cmH2O and the lymphatic pressure was 12.5 +/- 1.7 cmH2O. When we infused Ringer solution intravenously (10% body weight in approximately 50 min), the neck vein pressure increased to 17.3 +/- 0.9 cmH2O and the lymphatic pressure increased to 24.6 +/- 3.8 cmH2O (both P < 0.05). In two additional sheep, the thoracic duct lymph flow rate increased from 0.8 +/- 0.4 ml/min at baseline to 5.5 +/- 2.0 ml/min during the infusions. Our results show that postnodal intestinal lymphatic pressure may increase substantially during intravenous fluid infusions. This is important because increases in postnodal lymphatic pressure may slow lymph flow from the intestine. PMID- 8214168 TI - The linkage of health care reform and health services research. PMID- 8214167 TI - A quantitative method for classification of EEG in the fetal baboon. AB - Electroencephalographic (EEG) activity is used as a primary indicator of sleep states in adults and infants of many species and in the ovine fetus. We recently reported that the baboon fetus exhibits visually discernable patterns of EEG activity. One pattern of activity, characterized by the intermittent presence of repetitive bursts of high-voltage EEG, is indistinguishable from trace alternant (TA). TA is a distinctive pattern of EEG activity found only during early stages of development in primates. TA is the predominant pattern of EEG activity during quiet sleep in human infants < 2 mo of age. The focus of this study was to derive quantitative parameters that would discriminate TA from other activity and then to develop a method for automated categorization of EEG patterns. Results demonstrate that several parameters derived from frequency-domain analyses are related to visually coded EEG states. Among these parameters, high-frequency power (12-24 Hz) and spectral-edge frequency are good discriminators of EEG patterns. This paper describes a new parameter, EEG ratio, computed as spectral power in the rectified EEG within a band that corresponds to the frequency of bursts of activity during TA (0.03-0.20 Hz) divided by power in the 12- to 24-Hz band. This new composite parameter of EEG activity provides a markedly better correlate of visually coded EEG than any of the individual parameters tested. Using cluster analysis, we devised a method for objective minute-by-minute dichotomization of EEG ratio. The method produces results that agree with visual coding of EEG activity 87.1% of the time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214169 TI - Understanding the experience of schizophrenia. PMID- 8214170 TI - The DST as a predictor of outcome in depression: a meta-analysis. AB - OBJECTIVE: The authors undertook a review of the literature on the dexamethasone suppression test (DST) as a predictor of course and outcome in major depression, to illustrate clinical and pathophysiological implications of studying the relation between biological measures and course of illness in psychiatry. METHOD: In computerized searches and cross-references, 144 articles were found that related DST results to prediction of treatment response or outcome. Meta-analysis was performed on pooled data from all of the studies and separately on data from selected studies that had used stricter methodology. RESULTS: 1) Baseline DST status did not predict response to antidepressant treatment or outcome after hospital discharge. 2) Non-suppression of cortisol on the baseline DST predicted poorer response to placebo. 3) Persistent nonsuppression of cortisol on the DST after treatment was associated with high risk of early relapse and poor outcome after discharge. CONCLUSIONS: Baseline DST results may be devoid of prognostic value, but posttreatment nonsuppression of cortisol on the DST is strongly associated with poor outcome. Persistent nonsuppression may reflect a partially treated index episode or identify sicker patients who are unresponsive to treatment. The findings reiterate the importance of studying biological measures in relation to multiple validators of psychiatric illness beyond cross-sectional diagnosis. PMID- 8214171 TI - Follow-up of chronically homeless mentally ill men. AB - OBJECTIVE: To supply information on the efficacy of on-site day treatment for homeless mentally ill men in shelters, the authors followed up homeless mentally ill men 18 months after placement in community housing. METHOD: The 42 subjects had been evaluated before and 6 months after entering an on-site day treatment program. The authors reinterviewed 34 of these patients again 1 year after the first follow-up to determine housing status, hospitalization, aftercare, criminal justice contacts, income, and employment. RESULTS: By the 18-month follow-up the positive effects of the program at 6 months had deteriorated; 44% of the men had returned to shelters at some point during the follow-up period, and the number of men with criminal justice contacts had increased to a proportion exceeding that before the program. A concurrent diagnosis of substance abuse increased the risk of homelessness during follow-up. CONCLUSIONS: These findings underscore the need for innovative treatment and support services for the homeless mentally ill who have concurrent substance abuse. PMID- 8214172 TI - Use of psychopathology vignettes by patients with schizophrenia or schizoaffective disorder and by mental health professionals to judge patients' insight. AB - OBJECTIVE: The goal of this study was to clarify more precisely where patients with psychotic disorders and the mental health professionals who care for them disagree regarding whether the patient is ill or needs treatment. METHOD: The authors prepared brief vignettes in everyday descriptive language that provided examples of the classical positive and negative psychopathological features of schizophrenia. Fifteen men and 11 women diagnosed as having schizophrenia or schizoaffective disorder and one physician used these vignettes as a common frame of reference to rate 1) the degree to which the patients demonstrated the features described in each vignette and 2) the degree to which the features signified the presence of mental illness. RESULTS: Disagreements between the physician's and patients' ratings, indicating deficits in insight, were associated with the recognition of the presence of conceptual disorganization, avolition-apathy, and affective blunting in the patients by the physician but not the patients and with the conceptualization of hallucinatory behavior and suspiciousness as signs of mental illness by the physician but not the patients. CONCLUSIONS: The authors conclude that the failure to acknowledge conceptual disorganization, avolition-apathy, and affective blunting and the failure to view hallucinatory behavior and suspiciousness as signs of mental illness, which proved to be additive in this study, contribute to deficits in insight. PMID- 8214173 TI - Childhood precursors of schizophrenia: facial expressions of emotion. AB - OBJECTIVE: This study sought to determine whether affective abnormalities could be detected in home movies of children who later developed schizophrenia. METHOD: Trained observers coded facial expressions of emotion of 32 schizophrenic patients and 31 of their healthy siblings from home movies made when they were children. All of the patients met the DSM-III criteria for schizophrenia with onset in late adolescence or early adulthood. The sibling comparison subjects had no history of psychiatric illness. Nine emotions and a neutral category were rated. RESULTS: Analyses revealed significantly lower proportions of joy expressions among the total expressions of the preschizophrenic female subjects than among the same-sex healthy siblings. This difference extended from infancy through adolescence. Among the male subjects, there were inconsistent differences between diagnostic groups in expressions of joy across age levels. However, both the preschizophrenic male subjects and the preschizophrenic female subjects showed greater negative affect than their same-sex comparison groups. CONCLUSIONS: These findings lend support to the assumption that vulnerability to schizophrenia may be subtly manifested in emotional behavior long before the onset of clinical symptoms. PMID- 8214174 TI - "True" schizotypal personality disorder: a study of co-twins and relatives of schizophrenic probands. AB - OBJECTIVE: The aim of the study was to investigate the type and nature of personality disorders among biological relatives of schizophrenic probands. METHOD: A total of 176 nonschizophrenic co-twins and other first-degree relatives of schizophrenic probands were compared to 101 co-twins and first-degree relatives of probands with major depression. RESULTS: Schizotypal personality disorders were more common and histrionic personality disorders less common among the biological relatives of schizophrenic probands than among relatives of probands with major depression. A further exploration of the schizotypal criteria revealed that the so-called "negative" criteria such as odd speech, inappropriate affect, and odd behavior, as well as excessive social anxiety, were significantly more common among the relatives of schizophrenic probands. The latter criterion seems particularly important. The so-called "positive" schizotypal criteria were partly, although not statistically significantly, more common among the relatives of probands with major depression. There were only minor differences in frequencies of the negative criteria between monozygotic co-twins, dizygotic co twins, and other first-degree relatives of schizophrenic probands. CONCLUSIONS: The present study suggests that DSM-III-R schizotypal disorder is defined by a set of criteria that partly describe a "true" schizophrenia-related personality disorder and partly features that are not specific for relatives of schizophrenic probands. Furthermore, the genetic relationship between schizophrenia and "true" schizotypal personality disorder seems weak. Excessive social anxiety may be a marker of a possible genetic link between the disorders. PMID- 8214175 TI - Shifts in diagnostic frequencies of schizophrenia and major affective disorders at six North American psychiatric hospitals, 1972-1988. AB - OBJECTIVE: This study tested the impression that there have been significant shifts in the relative diagnostic frequencies of schizophrenia and major affective disorders. METHOD: Data on discharge diagnoses from 1972 to 1988 were gathered from six North American psychiatric teaching hospitals (data from one extended through 1991), and rates for schizophrenia and major mood disorders were evaluated. RESULTS: Total annual discharges increased by 6.6% during the study period. Large reciprocal shifts in the frequencies of diagnoses of schizophrenia and major affective disorders were found; schizoaffective disorder was a minor diagnosis. Beginning in the early 1970s, a gradual increase in the frequency of diagnoses of major affective disorders at all sites was accompanied by a corresponding decrease in diagnoses of schizophrenia at five of the six centers. Schizophrenia diagnoses decreased from a peak of 27% in 1976 to 9% in 1989 (a threefold decrease), and diagnoses of major affective disorders rose from a low of 10% in 1972 to 44% in 1990 (a fourfold increase). CONCLUSIONS: Several forces may have influenced these changes. 1) DSM-III narrowed the definition of schizophrenia and broadened the category of major affective disorders. 2) Treatment-oriented diagnostic bias associated with the availability of lithium and other mood-altering agents may have encouraged consideration of affective disorders. 3) Economic and social forces, including better third-party reimbursement rates, may have favored affective diagnoses. 4) True increases in the incidence of affective disorders may have occurred. 5) Although a real decrease in new cases of schizophrenia may have occurred, this effect was probably minor and dominated by a larger shift of such diagnoses to affective categories. PMID- 8214176 TI - Cortisol levels, immune status, and mood in homosexual men with and without HIV infection. AB - OBJECTIVE: Alteration in cortisol levels has been reported in HIV infection and may be related to levels of psychiatric distress and immune function. The goals of this study were to assess cortisol levels in subjects with HIV infection and to determine whether stress-related activation of the hypothalamic-pituitary adrenal (HPA) axis results in compromised immune function. METHOD: As part of a longitudinal study, the authors assessed urinary free cortisol levels of HIV positive and HIV-negative homosexual men at four time points during a period of 2 years. Subjects' scores on the Hamilton depression and anxiety rating scales, medical stage of HIV infection, and CD4+ and CD8+ cell counts were also assessed. Repeated measures analysis of variance was used to determine whether subjects' cortisol levels at the four time points differed according to their serological status. Pearson correlation coefficients were computed to examine the relationships among mood ratings, cortisol levels, medical stages, and cell counts. RESULTS: Cortisol levels did not differ significantly between the HIV positive and the HIV-negative subjects and were not associated with stage of medical illness in HIV infection. An association between cortisol level and depressed and anxious mood was found only at the first assessment. Cortisol level was not associated with CD4+ cell count in either group of subjects. CONCLUSIONS: There were no significant elevations of cortisol levels in the HIV-infected subjects, nor was there consistent evidence for stress-related activation of the HPA axis in either the HIV-positive or the HIV-negative subjects. PMID- 8214177 TI - Outcome of cognitive-behavioral and support group brief therapies for depressed, HIV-infected persons. AB - OBJECTIVE: Although many studies have documented patterns of emotional distress in persons with HIV disease, there have been few controlled evaluations of therapy outcomes with these individuals. This research evaluated the effects of brief cognitive-behavioral or social support group therapy with this population. METHOD: Sixty-eight depressed men with HIV infection were randomly assigned to one of three conditions: eight-session cognitive-behavioral groups, eight-session social support groups, or a comparison condition. Before and after intervention and at 3-month follow-up, all participants were individually assessed by using measures of symptoms of distress as well as substance use and sexual practices. RESULTS: Relative to the comparison group, both the cognitive-behavioral and social support group therapies produced reductions in depression, hostility, and somatization. The social support intervention also produced reductions in overall psychiatric symptoms and tended to reduce maladaptive interpersonal sensitivity, anxiety, and frequency of unprotected receptive anal intercourse, while the cognitive-behavioral intervention resulted in less frequent illicit drug use during the follow-up period. Tests for clinical significance of change particularly underscored benefits of the social support group intervention both at postintervention and at long-term follow-up. CONCLUSIONS: Brief group therapy for depressed persons with HIV infection produced reductions in symptoms of distress. The two forms of therapy resulted in shared and unique improvements in functioning, although social support groups focused on emotional coping presented greater evidence of clinically significant change. As more persons contract HIV infection and live longer with HIV disease, further research is needed to evaluate outcomes of mental health services with these individuals. PMID- 8214178 TI - Factors associated with suicide attempts by depressed older adults: a prospective study. AB - OBJECTIVE: This study sought to ascertain demographic, clinical, and interpersonal factors prospectively associated with suicide attempts by older adults with major depressive disorder. METHOD: Elderly inpatients diagnosed as having major depressive disorder according to the Research Diagnostic Criteria were administered a structured diagnostic interview and then followed up for 1 year. Factors bearing on the interpersonal context of depression, including the emotional adjustment of patients' spouses and adult children, interpersonal strains, and relatives' concerns related to the care of their depressed family members, were also ascertained at the time of the patients' hospital admission. The elderly patients who attempted suicide during the follow-up period were compared with the nonattempters across demographic, clinical, and interpersonal factors assessed during the initial interviews. RESULTS: A suicide attempt was made by 8.7% (N = 11) of the 126 elderly depressed patients within 1 year after hospital admission. Compared with the nonattempters, the attempters were of a higher socioeconomic status, evidenced more past suicide attempts and current suicidal behavior, and constituted a disproportionately large percentage of those patients who had never had a remission of their index depressive episodes. Notably, the spouses and adult children of patients who later attempted suicide evidenced more psychiatric symptoms, more strain in the relative-patient relationship, and more difficulties in caring for the patient than the relatives of nonattempters. CONCLUSIONS: The findings emphasize the need for careful attention to both clinical and interpersonal factors in the assessment of suicide risk in the elderly. PMID- 8214179 TI - Group psychotherapy during radiotherapy: effects on emotional and physical distress. AB - OBJECTIVE: The purpose of this study was to ascertain whether group psychotherapy during radiotherapy for cancer significantly decreases patients' emotional and physical distress. METHOD: Twenty-four patients receiving radiotherapy were randomly selected for group psychotherapy (six patients per group, 90-minute weekly sessions for 10 weeks). Another 24 patients served as control subjects. Each patient was given the Schedule for Affective Disorders and Schizophrenia (SADS) at the onset of radiotherapy, midway through radiotherapy, at the end of radiotherapy, and 4 and 8 weeks after radiotherapy ended. RESULTS: The combined SADS items for depression, pessimism and hopelessness, somatic preoccupation and worry, social isolation and withdrawal, insomnia, and anxiety and agitation were used as a measure of emotional distress. The combined SADS items for anorexia, nausea and vomiting, and fatigue were used as a measure of physical distress. By 4 weeks after the end of radiotherapy, the patients who received group psychotherapy showed significant decreases in both emotional and physical symptoms, and the decreases were greater than those for the control patients. The subjects who initially seemed unaware of their cancer diagnoses had the lowest baseline levels of emotional and physical distress, but 4 weeks after the end of radiotherapy they had high distress levels. CONCLUSIONS: Group therapy may enhance quality of life for cancer patients undergoing radiotherapy by reducing their emotional and physical distress. The degree to which patients acknowledge the diagnosis of malignancy may be a factor in their initial distress level and their response to radiotherapy and group therapy. PMID- 8214180 TI - Gender differences in substance use disorders. AB - OBJECTIVE: The goals of this study were to explore gender differences in demographic variables, psychiatric comorbidity, and personality disorders in individuals with substance use disorders. METHOD: A total of 100 treatment seeking substance users (50 men and 50 women) admitted to a university-based and a university-affiliated private chemical dependency hospital were compared with regard to demographic variables and comorbid psychiatric and personality diagnosis according to the Structured Clinical Interview for DSM-III-R after 14 21 days in treatment. RESULTS: Men were significantly more likely to have a higher household income and to be alcohol dependent. Women were significantly more likely to have another axis I disorder in addition to substance use disorder, particularly anxiety disorders, but these gender differences were not substantially different from the gender prevalence of these disorders in the general population. Men had more affective disorders relative to women than would be expected from the general population data. Female alcoholics had substantially more psychopathology than male alcoholics, and generally these differences were consistent with the ratios of these disorders in the general population. For cocaine users, female/male ratios of anxiety and affective disorders were inconsistent with general population ratios and indicated more psychopathology than would be expected in male cocaine users. There were no gender differences in axis II diagnoses. CONCLUSIONS: Some of the gender differences in psychopathology in substance users are at odds with gender differences for psychopathology in the general population. Further exploration of these differences could have important theoretical and treatment implications. PMID- 8214181 TI - Sensitivity to subjective effects of cocaine in drug abusers: relationship to cerebral ventricle size. AB - OBJECTIVE: The purpose of this study was to assess the functional significance of ventricle-brain ratio (VBR) in terms of how it might affect sensitivity to cocaine, an indirect dopamine agonist. METHOD: Relationships between VBR and subjective responses to acute intravenous cocaine hydrochloride were examined in 20 male polydrug abusers. Tests were performed in conjunction with positron emission tomography scans to measure cerebral glucose metabolism. RESULTS: Subjective measures of effects of cocaine, including self-report ratings of intensity of the drug effect, scores on the morphine-benzedrine scale of the Addiction Research Center Inventory, and several items on visual analogue scales, correlated negatively with VBR. VBR also differed significantly among subjects who were grouped according to scores on items ("rush" and "crash") of the Cocaine Sensitive Scale (larger VBR in subjects with weaker responses). VBR was not correlated with cocaine-induced changes in cerebral metabolic rates for glucose. CONCLUSIONS: Relative insensitivity to the subjective effects of cocaine in polydrug abusers with ventricle enlargement suggests that ventriculomegaly may reflect changes in periventricular brain regions that mediate these effects of cocaine. PMID- 8214182 TI - Depressive personality in nonclinical subjects. AB - OBJECTIVE: This study explored the reliability and clinical correlates of the depressive personality in nonclinical subjects. In particular, the authors were interested in determining the relationship between depressive personality and mood disorders. METHOD: The subjects were 185 college students who were selected by using a battery of screening inventories assessing a variety of psychopathological symptoms and traits. The subjects were given structured diagnostic interviews that included a section on depressive temperament. RESULTS: There were significant relationships between depressive personality and lifetime. DSM-III diagnoses of major depression and dysthymia. However, the magnitude of the associations was modest, indicating that these are distinct, although overlapping constructs. In addition, the subjects with depressive personality (N = 36) had significantly greater impairment and a higher rate of mood disorders in their first-degree relatives than did the subjects without depressive personality (N = 149). Moreover, these results were evident even after the subjects with a lifetime history of mood disorder were excluded. CONCLUSIONS: These data suggest that depressive personality is a clinically important condition that is not subsumed by existing mood disorders categories but can be viewed as falling within the affective spectrum. PMID- 8214183 TI - Alzheimer's-disease-related protein in geriatric schizophrenic patients with cognitive impairment. AB - The authors compared Alz-50 immunoreactivity in the brain tissue of nine cognitively impaired elderly schizophrenic patients and 13 elderly comparison subjects, both without neuritic plaques or neurofibrillary tangles, and 13 patients with Alzheimer's disease. Alz-50 reactivity was absent in the schizophrenic patients, indicating that geriatric, cognitively impaired patients are unlikely to display the pathology of Alzheimer's disease. PMID- 8214184 TI - Baclofen-induced growth hormone release in major depression: relationship to dexamethasone suppression test result. AB - Fifteen patients with DSM-III-R major depression and 15 matched comparison subjects underwent baclofen-induced growth hormone (GH) release and the dexamethasone suppression test (DST). The GH responses of the patients were significantly blunted, especially those of the patients who were DST nonsuppressors. These findings may indicate lower than normal responsivity of type B gamma-aminobutyric acid (GABA-B) receptors in depression and a relationship between GABA-B receptor abnormality and dysfunction of the hypothalamic-pituitary-adrenal axis. PMID- 8214185 TI - Plasma and platelet excitatory amino acids in psychiatric disorders. AB - Plasma and platelet levels of excitatory amino acids were measured in 38 psychiatric out-patients and in 19 comparison subjects; the patients had DSM-III R diagnoses of organic mental disorders (N = 3), mood disorders (N = 15), schizophrenia (N = 13), and anxiety disorders (N = 7). The glutamate plasma levels were significantly higher in the patients with mood disorders than in the comparison group. PMID- 8214186 TI - Gender differences in clinical characteristics of first-admission psychotic depression. AB - The authors explored differences in the clinical characteristics of 17 male and 13 female patients experiencing their first admission for psychotic depression. Few differences were observed for most depressive and psychotic features, but fewer male than female patients reported fatigue, psychomotor agitation, and systematized and mood-incongruent delusions and more male patients reported feelings of worthlessness. Overall, the findings were consistent with those derived from samples of patients with chronic, nonpsychotic mental illness. PMID- 8214187 TI - Computer-assisted telephone administration of a structured interview for obsessive-compulsive disorder. AB - A computer-assisted telephone system using digitized human speech was developed to administer two rating scales for obsessive-compulsive disorder. For 18 patients, scores derived with this system agreed well with scores from human administration of the scales by telephone and paper-and-pencil scales returned by mail. This approach provides reliable, low-cost, and instantaneous data acquisition. PMID- 8214188 TI - Dopaminergic hallucinosis with fluoxetine in Parkinson's disease. PMID- 8214189 TI - Transient thrombocytopenia while continuing carbamazepine. PMID- 8214190 TI - An interaction of sertraline and desipramine. PMID- 8214191 TI - Fluoxetine-pimozide interaction. PMID- 8214192 TI - Seasonal bulimia treated with fluoxetine and phototherapy. PMID- 8214193 TI - Neuroleptic-induced extrapyramidal side effects. PMID- 8214194 TI - Sertraline in the treatment of bulimia nervosa. PMID- 8214195 TI - First quarter births in Alzheimer's disease. PMID- 8214196 TI - Schizophrenia research. PMID- 8214197 TI - Cocaine abuse among methadone-maintained patients. PMID- 8214198 TI - The eye roll sign and psychopathology. PMID- 8214200 TI - Anticholinergic effects of drugs for the elderly. PMID- 8214199 TI - Refractoriness induced by lithium discontinuation. PMID- 8214201 TI - Visual hallucinations in macular degeneration. PMID- 8214202 TI - The issue of side effects and the "blind ability" of clinical drug trials. PMID- 8214203 TI - The issue of side effects and the "blind ability" of clinical drug trials. PMID- 8214204 TI - beta-Endorphin and specific clinical symptoms of depression. PMID- 8214205 TI - The conflict and process theory of Melanie Klein. AB - This article depicts the theory of Melanie Klein in both its conflict and process dimensions. In addition, it outlines Klein's strategic place in psychoanalytic history and in psychoanalytic theory formation. Her major contributions are seen in light of their clinical imperatives, and aspects of her metapsychology that seem negligible are differentiated from these clinical imperatives. Klein's role as a dialectical fulcrum between drive and object relations theories is explicated. Within the conflict theory, drive derivatives of sex and aggression are reformulated as object-related passions of love and hate. The process dimensions of Klein's theory are outlined in terms of dialectical increments of depressive position process as it alternates with regressive paranoid-schizoid position mental phenomenology. The mourning process as a developmental process is particularly high-lighted in terms of self-integrative progression within the working through of the depressive position. PMID- 8214206 TI - Dora: desire and ambiguity in the fragment of a psychoanalysis. PMID- 8214207 TI - On typographical errors. AB - In his overall assessment of parapraxes in 1901, Freud included typographical mistakes but did not elaborate on or study this subject nor did he have anything to say about it in his later writings. This paper lists textual errors from a variety of current literary sources and explores the dynamic importance of their execution and the failure to make necessary corrections during the editorial process. While there has been a deemphasis of the role of unconscious determinants in the genesis of all slips as a result of recent findings in cognitive psychology, the examples offered suggest that, with respect to motivation, lapses in compulsivity contribute to their original commission while thematic compliance and voyeuristic issues are important in their not being discovered prior to publication. PMID- 8214208 TI - Parapraxes in song recall: a neglected variable. AB - In addition to expressing themselves with verbal and nonverbal communications, and by the countertransference reactions perceived by analysts, patients also reveal their inner world of images and feelings specifically with music evocations. This paper presents an initial attempt to identify and classify some of the parapraxes produced in the evocation of lyrics and music by polyglot members of treatment dyads in two empirical studies and in private practice. There may be many others, particularly related to the music per se. This paper has focused mainly on the lyrics, the equivalent of the manifest content of dreams, which nonmusician therapists can learn to handle well. Instead, in the case of the musical latent content, some knowledge of music is necessary. Supervisors' songs were considered beyond the scope of this paper and will be addressed separately. Parapraxes in song recall signal unconscious transference countertransference states in process at the moment of evocation. PMID- 8214209 TI - Studies in feminine psychology 6: Kundry. AB - The problem of feminine rage, feminine psychology, and feminine self-destruction must be understood as multiply determined and not merely an appropriate manifestation of social inequality in a male-dominated culture. This is illustrated by a study of pathological and borderline women, in the present paper represented by Wagner's creation from Parsifal, Kundry. Kundry suffers from pathological splitting, in which she oscillates from mature nurturing service to hatred, seduction, and destruction of men. What is most emphasized is her misery and guilt, which is a consequence of her reality testing being sufficiently intact for her to be aware of this splitting and its consequences for her. She receives no understanding from the men around her; even the hero or "pure fool" Parsifal at first attempts to strangle her like an animal. But Wagner's intuition emphasizes her conflict and guilt rather than the splitting and deficits, making her redemption possible. This approach to borderline psychopathology has a more hopeful prognosis, given the presence of a dedicated, determined, and competent psychoanalytic psychotherapist. PMID- 8214210 TI - Psychoanalytic teachings of the Talmud. PMID- 8214212 TI - Adolescent psychotherapy research: a practical review. AB - Most of the review studies, including meta-analyses that pay special attention to internal and external validity, support the efficacy of individual psychotherapy for children and adolescent. However, methodological flaws in existing research on outcome of this form of therapy prevents us from getting incontrovertible proof. This paper reviews these studies, emphasizes factors thought to be important to the outcome--variables such as the development process, family and environment, the young person's motivation for therapy, etc.--that have to be taken into consideration by researchers. Special recommendations for the design of future research are offered. PMID- 8214211 TI - Psychotherapy under siege. PMID- 8214213 TI - Adolescence, social development, and psychotherapy. AB - Based on a clinical theory that guides an interpersonal approach to adolescent psychotherapy, the author advances the proposal that there is a developmental sequence of the capacity for relatedness from early to late adolescence: from a stage of Detachment in Relatedness through Disappointment in Relatedness to Mature Relatedness. In this paper, evidence from several broad-based studies of the social development of normal adolescents is presented in support of this proposal. These studies have attempted to track the developmental changes in intimacy, peer conformity, and qualities of friendship. PMID- 8214214 TI - Issues unique to psychotherapy with adolescent girls. AB - New research on development and risk factors has increased our knowledge of adolescent girls and given those of us working with them more available information to aid our understanding of psychotherapy. Advancing social theory has also promoted an understanding of the problems that adolescent girls begin to face including gender discrimination and conflict around social roles. Educated therapists can utilize this information with their adolescent female patients, providing knowledge about choices available to girls and promoting understanding and problem-solving. Growing knowledge about the importance of relationships for this population also informs us about the therapeutic alliance. In summary, therapists working with adolescent girls face many challenges and also have increasing access to information that can aid them with this process. PMID- 8214215 TI - Brief psychotherapy with adolescents: individual and family approaches. AB - Brief psychotherapy with adolescents is a widely employed clinical procedure. In this paper key principles that inform brief individual and family therapy with adolescents have been described. The most important principle is to establish and maintain a therapeutic relationship with the teen; the second most important principle is to find a focal theme or focal point for mutual work. Many adolescents respond well to a course of brief therapy arbitrarily defined here as 20 or fewer sessions. While such an approach is not "curative," it does provide the opportunity for substantial symptom relief and improved adaptation. In selecting patients for brief therapy negative exclusion factors are more helpful than positive inclusion factors. If the teen experiences brief therapy as a positive intervention, the road is paved for his/her return if and when future problems arise. Economic pressures during the next decade will favor brief therapy over long-term therapy. The most adaptive response for therapists to this challenge is to improve their brief therapy skills. A frequently neglected skill is the ability to set modest but achievable goals in brief psychotherapy. Finding a focus for therapy lays the foundation for reasonable goal-setting. PMID- 8214216 TI - The relationship between psychotherapy and pharmacotherapy: an introduction. PMID- 8214217 TI - The psychotherapy of giving medications: therapeutic techniques for interpersonal interventions. AB - We believe that the duration and mileu of medication visits can be appropriately and effectively used for ongoing psychotherapy in patients who must come for the prescription and follow-up of psychiatric medications. Many physicians make unplanned therapeutic suggestions as a matter of course; in contrast, when interventions are planned, codified, and examined with respect to patient's needs and physician's personal internal responses, their effectiveness and consistency can be enhanced. Specific interventions such as role modeling mental health, identifying transference reactions, and addressing family systems process are easily and effectively made, without being onerous or threatening to patients with severe mental illness. Overall, our clinical experience suggests that planned psychotherapy can be advantageously combined with pharmacologic treatment to enhance patients' overall response. PMID- 8214218 TI - The interaction between pharmacotherapy and psychotherapy in the treatment of posttraumatic stress disorder. AB - For patients with PTSD, the effective initiation of additional therapeutic modalities to ongoing individual psychotherapy is challenging. When pharmacologic agents are added, the therapist must carefully consider and monitor the impact of medications on PTSD core symptoms and on adjunctive symptoms such as depression. Further considerations include issues of countertransference, the possible symbolic meaning of medications for both the patient and the therapist, and the appropriate staging of medications. When nonphysician treaters work together with a medical back-up, both parties should frequently communicate with one another in order to avoid unnecessary treatment distortions and disruptions. PMID- 8214219 TI - Psychotherapy vs. pharmacotherapy: are psychiatrists polarized?--A survey of academic and clinical faculty. AB - Recent debate about the Osheroff vs. Chestnut Lodge case has highlighted the potential for polarization in psychiatric treatment. The degree to which community clinical psychiatric practice is polarized between psychological and biological treatments is not known. There are limitations in the combined treatment studies performed to date that influence their applicability to treatment planning in the community setting. A nearly exclusive focus on mood disorders and a neglect of the role of concurrent personality disorders and treatment interactions are among these. The data base available to guide a truly integrated practice of differential therapeutics is therefore quite limited. Against this background, we surveyed academic and clinical psychiatric faculty to determine treatment practices and rationales in three case with both Axis I and Axis II diagnoses. In each case, greater than 75% would utilize psychotherapy and consider its omission inappropriate. Medication use varied significantly from case to case. Our findings suggest that practicing psychiatrists combine psychotherapy and pharmacotherapy and that the perceived polarization between "biological" and "psychosocial" psychiatry may be more a matter of "philosophy" than practice. PMID- 8214220 TI - Insanity and war: the Gulf War and a psychiatric institution. AB - The threat of a chemical war has profound impacts on all layers of society. Hospitalized mental patients, as we have observed them, react in more extreme ways than staff members. They may react overanxiously, totally apathetically, or in context-related flights to partial sanity. Denial and projection were heavily used defense mechanisms together with a tendency of the more acute patients to plunge into their bizarre idiosyncratic world, lending strange meanings to what was happening in the world. Many patients were found to have strong narcissistic traits and to invest most of their libidinal energies in their private world. In times of stress this results in even greater social isolation. Different types of patients in different phases of their illness react differently to such overpowering stress, and the way they react illustrates their cognitive, behavioral, and social deficiencies. WWII literature on the reactions of mentally ill patients to "fly-bombing" seem not to take into consideration the different possible reactions of patients. This may be due to a change in emphasis in the care of mentally disturbed individuals in the last two decades. We propose to use even such an extremely stressful situation as a challenge to the mental health profession to further the well-being of their patients. PMID- 8214221 TI - Therapeutic wisdom in Indian mythology. AB - The usefulness of anecdotal analogies from Indian mythology in therapeutic work with rural mental health patients has been reported. The author encountered evidences for the same in his clinical work. He then undertook to collect from Indian mythological literature excerpts containing psychotherapeutic and related themes. Examples of a few of those themes are presented to stimulate the interest of therapists in the vast therapeutic potential in mythologies. The mental health profession would benefit from examining mythologies of other cultures, and experimenting in using them in therapy. PMID- 8214222 TI - We are all Berliners: notes from the Ninth International Conference on AIDS. PMID- 8214223 TI - HIV prevention: an update on the status of methods women can use. PMID- 8214224 TI - When ideals meet reality--the global challenge of HIV/AIDS. PMID- 8214225 TI - Clinical research, prophylaxis, therapy, and care for HIV disease in Africa. AB - By the end of the century, citizens of resource-poor countries will constitute 90% of the world's human immunodeficiency virus (HIV)-infected people. Clinical management of such persons in developing countries has been neglected; most AIDS research has concentrated on epidemiology, and donor agencies have generally invested in the prevention of HIV infection. The heavy burden of HIV disease in Africa requires that care for AIDS be addressed, and prevention and care should be seen as interrelated. Prevention and treatment of tuberculosis, the commonest severe infection in persons with AIDS in Africa, illustrate this interrelationship. We outline priorities for applied research on the management of HIV disease in a resource-poor environment, and discuss prophylaxis, therapy for opportunistic diseases, terminal care, and use of antiretroviral therapy. Research should define the standard of care that can realistically be demanded for HIV disease in a resource-poor environment. Research and public health programs for AIDS in developing countries must address AIDS care and attempt to reduce the widening gap between interventions available for HIV-infected persons in different parts of the world. PMID- 8214226 TI - HIV-1 seroprevalence and risk behaviors in an urban African-American community cohort. AB - OBJECTIVES: Previous attempts at obtaining population estimates of human immunodeficiency virus type 1 (HIV-1) seroprevalence have been beset by problems of cooperation bias. As part of the fourth round of study with an urban African American community cohort, the following investigation was aimed at assessing HIV 1 prevalence and the relative importance of sex and drug injection as risk factors in infection. METHODS: Personal interviews were conducted in the home with 364 respondents, followed by voluntary blood sample collection from 287 of these individuals. RESULTS: Blood assays showed a point prevalence of 8.4% HIV-1 seropositivity in this community cross section, with a higher female-to-male ratio than appears among acquired immunodeficiency syndrome (AIDS) case reports. Most infected persons were unaware and unsuspecting of their infection. CONCLUSIONS: First, findings underscore the need to focus on risk behaviors rather than on risk groups. Second, the smaller than 2:1 ratio of infected men to women suggests that current AIDS case reports seriously underestimate HIV-1 infection among certain cohorts of African-American women. Finally, widespread ignorance of own infected status and inaccurate risk assessment signal the substantial task for community health educators in reaching inner-city African American men and women at risk. PMID- 8214227 TI - HIV risk among Latino adolescents in two New England cities. AB - OBJECTIVES: Latino adolescents in two urban New England areas were surveyed to assess risk of human immunodeficiency virus (HIV) transmission. METHODS: Probability of HIV infection during the previous 6 months was estimated from self reported sexual contacts, condom usage rates, and number of partners. Teens were also asked to show condoms in their possession to the interviewer to validate self-reports of condom use. RESULTS: Overall, 8% of the 586 respondents were classified as high risk for HIV infection (estimated infection probability greater than .0001), 34% were at moderate risk, and the remaining 58% were classified as not at risk (no sexual activity or needle sharing). Teens who said they had purchased condoms or claimed to have used them recently were more likely than others to have condoms in their possession at the time of the interview. CONCLUSIONS: These estimates suggest that a small percentage of Latino adolescents may be at substantial risk for HIV infection over periods as short as 6 months, that self-reports of recent condom use are strongly related to condom possession, and that questionnaire items regarding condom use at last intercourse are poor surrogates for HIV risk. PMID- 8214228 TI - The sexual behavior of US adults: results from a national survey. AB - OBJECTIVES: One consequence of the acquired immunodeficiency syndrome (AIDS) epidemic has been to highlight the need for population-based estimates of the number of individuals engaging in sexual behaviors that place them at risk for human immunodeficiency virus (HIV) infection. This paper describes the prevalence of various sexual behaviors in a nationally representative sample of adults in the United States. METHODS: Data were collected as part of a household probability survey of adults (n = 2058) in the United States. Data collected on sexual behavior included sexual orientation, frequency of intercourse, condom use, and number of sexual partners. RESULTS: Nearly all respondents were sexually experienced. Of those who were currently sexually active, 13% (1% of married respondents) had had sex with more than one partner in the previous year. Of those reporting having intercourse with more than one partner in the previous year, 7% used condoms consistently and 23% used condoms consistently with their casual partners. CONCLUSIONS: A significant proportion of individuals were found to have intercourse with multiple partners without using condoms. A minority of these respondents acknowledged that their behavior may place them at risk for HIV transmission. PMID- 8214229 TI - Estimated condom failure and frequency of condom use among gay men. AB - OBJECTIVES: Condoms are designed to bar transmission of the human immunodeficiency virus (HIV), but they sometimes fail. This paper explores the effect of experience with condoms on condom failure among gay men. METHODS: Risk of condom failure (breakage or slippage) on a single occasion is estimated for four sexual acts reported over 12 months by a sample of gay New York City men (n = 741). The estimation procedure assumes that each episode in which a condom is used is an independent event. Evidence is offered to support this assumption. RESULTS: Risk of condom failure in a single episode was fairly high, particularly in anal intercourse, for men who had engaged in each act only a few times in the previous year. It declined rapidly with experience (e.g., to below 1% for receptive anal intercourse after about 10 episodes in the previous year). Condoms failed less often in oral than anal sex, but estimated risk of failure also decreased with experience. CONCLUSIONS: Gay men should be especially cautious the first few times they use a condom; after moderate experience, however, they may expect a low risk of condom failure. PMID- 8214230 TI - Are HIV-infected injection drug users taking HIV tests? AB - OBJECTIVES: Knowledge of infection is essential for human immunodeficiency virus type 1 (HIV-1) treatment initiation and epidemic control. This study evaluates infection knowledge among infected injection drug users and acceptance of confidential testing among injection drug users, particularly those infected with HIV-1. METHODS: A total of 810 injection drug users entering treatment in Contra Costa County, Calif, were examined. Clients were tested with unlinked (blinded) tests and simultaneously counseled and offered voluntary confidential HIV-1 antibody testing. Data on confidential testing acceptance, previous testing, drug use, and demographic information were collected. RESULTS: Of the 810 tested, 105 (13.0%) were infected. The current confidential test was accepted by 507 (62.6%). HIV seroprevalence in the unlinked survey was four times greater than in the voluntary survey (13% and 3.5%, respectively). HIV-1 infection was associated with refusal of a confidential test largely because most infected injection drug users (n = 58; 55.2%) already knew of their infection. Of the 47 injection drug users who were not aware of their infection, 12 (25.5%) accepted the test. Although African-American injection drug users presented with a higher infection rate (37.3%), they were three times less likely to know of their infection. CONCLUSIONS: "In-clinic" HIV-1 testing is highly accepted, and most infected clients in treatment will learn their status. Nevertheless, voluntary testing data are likely to yield considerable underestimates of the true rate of infection among injection drug users. PMID- 8214231 TI - Partner notification for control of HIV: results after 2 years of a statewide program in Utah. AB - OBJECTIVES: We sought to evaluate the utility of partner notification for control of human immunodeficiency virus (HIV) infection and to identify subgroups in which it may be most effective. METHODS: All persons reported to be HIV-positive during a 2-year period were interviewed. Outcome measures included proportion of index patients cooperating; number of partners named, located, counseled, and tested; number of persons newly testing positive; and costs. RESULTS: Of 308 index patients, 244 (79%) cooperated. They named 890 partners; 499 (70%) of in state partners were located. Of these, 154 (34%) had previously tested HIV positive. Of 279 partners tested for the first time, 39 (14%) were HIV-positive. Injecting drug users were significantly more likely to cooperate than persons in other risk groups (93% vs 76%) and named more partners (median 4 vs 1). Women and persons choosing confidential testing were more likely to cooperate and named more partners. The estimated cost of the program was $62,500 per year. CONCLUSIONS: Partner notification identified a group with a high seroprevalence of HIV. It was not successful among populations that may be difficult to reach with other interventions. PMID- 8214232 TI - Race and survival time with AIDS: a synthesis of the literature. AB - OBJECTIVE: This study summarizes the evidence concerning the association of Black and White race with acquired immunodeficiency syndrome (AIDS) survival time. METHODS: English-language articles measuring survival time with AIDS for Black and White persons were reviewed. Each article was assigned to one of three groups based on the method of subject accrual. RESULTS: Of the nine eligible studies identified, five studies had inclusive methods of accruing study subjects, and four of these five showed decreased survival time among Black persons. In the studies with more restrictive accrual methods, survival time for Blacks was not decreased. CONCLUSIONS: Although the published studies vary in their results, this variation appears to be systematic according to the method of accruing study subjects. If the accrual method serves to minimize socioeconomic differences between Blacks and Whites, there is no difference in survival time by race. However, if a more inclusive method is used, a significant decrease in AIDS survival time is observed among Blacks. This analysis suggests that, in some studies, race may function as a marker for socioeconomic factors and/or access to health care and that AIDS patients in the lowest socioeconomic or access group have significantly shorter survival times. PMID- 8214233 TI - Causes of death among persons reported with AIDS. AB - OBJECTIVES: This study describes causes of death in persons with acquired immunodeficiency syndrome (AIDS) and assesses the completeness of reporting of human immunodeficiency virus (HIV) infection or AIDS on death certificates of persons with AIDS. METHODS: AIDS case reports were linked with death certificates in 11 local/state health departments; underlying and associated causes of death were available for 32,513 persons with AIDS who died. RESULTS: HIV/AIDS was designated as the underlying cause of death for 46% of persons with AIDS who died between 1983 and 1986 and 81% of persons with AIDS who died since 1987 (the year specific coding procedures were implemented for HIV/AIDS). Most other underlying causes of death were conditions within the AIDS case definition (notably Pneumocystis carinii pneumonia), pneumonia, infections outside the AIDS case definition, and drug abuse. Unintentional injuries, suicide, and homicide were less common. HIV/AIDS was listed as underlying or associated on 88% of death certificates from 1987 to 1989; reporting varied primarily by HIV exposure category and time between diagnosis and death. CONCLUSIONS: Physicians and other health care professionals should realize their critical role in accurately documenting HIV-related mortality on death certificates. Such data can ultimately influence the allocation of health care resources for HIV-infected individuals. PMID- 8214234 TI - AIDS deaths shift from hospital to home. AIDS Mortality Project Group. AB - OBJECTIVE: This study monitors trends in place of death among persons with acquired immunodeficiency syndrome (AIDS) as a measure of health care usage patterns and terminal health care among persons infected with human immunodeficiency virus (HIV). METHODS: Sixteen health departments collected death certificates for 55,186 persons with AIDS whose deaths occurred through 1991. Place of death was categorized as hospital, residence, hospice or nursing home, and other. RESULTS: The percentage of AIDS deaths at hospital facilities decreased from 92% in 1983 to 57% in 1991. In 1988, 23% of deaths occurred at home or in hospices and nursing homes. This trend was more evident among men, Whites, and men who had sex with men; less so among persons with other modes of exposure; and not at all among injecting drug users and children with perinatally acquired AIDS. Place of death varied by geographic location, with the greatest percentage of hospital deaths in the Northeast (91%) and the greatest percentage of at-home deaths in the West (27%). CONCLUSIONS: The percentage of AIDS deaths at home or in hospices and nursing homes has increased since 1983. These trends may reflect changes in hospital use for end-stage HIV infection. Decreasing hospitalization and increasing outpatient services and home care will decrease costs and may allow HIV-infected persons improved social support. PMID- 8214235 TI - HIV-related knowledge and precautions among Michigan nurses. AB - OBJECTIVES: The present study examined human immunodeficiency virus (HIV)-related knowledge and precautionary behaviors in a large random sample of registered nurses in all regions of the state of Michigan, allowing for comparisons among nurses in a wide range of occupational experiences, exposures, and backgrounds related to HIV. METHODS: A random sample of all registered nurses living in Michigan completed surveys in the fall of 1989. RESULTS: Although nearly all respondents indicated a high level of knowledge of known viable routes of HIV transmission, many respondents also reported misconceptions about several unverified nonviable routes of HIV transmission. Of the respondents who were involved in situations with potential risk of exposure to HIV, many failed to consistently use the universal precautions recommended by the Centers for Disease Control and Prevention. The respondents also reported significant barriers in applying infection control procedures. CONCLUSIONS: The findings of the present study support the need for continued and intensified efforts to ensure that nurses have the knowledge necessary to provide quality care, are aware of the risk of potential exposures to HIV, and are engaging in appropriate precautionary behaviors. PMID- 8214236 TI - Risk due to inactivity in physically capable older adults. AB - OBJECTIVES: This study examined the association between recreational physical activity among physically capable older adults and functional status, incidence of selected chronic conditions, and mortality over 3 and 6 years. METHODS: Data are from three sites of the Established Populations for Epidemiologic Studies of the Elderly. RESULTS: A high level of recreational physical activity reduced the likelihood of mortality over both 3 and 6 years. Moderate to high activity reduced the risk of physical impairments over 3 years; this effect diminishes after 6 years. A consistent relationship between activity and new myocardial infarction or stroke or the incidence of diabetes or angina was not found after 3 or 6 years. CONCLUSIONS: Findings suggest that physical activity offers benefits to physically capable older adults, primarily in reducing the risk of functional decline and mortality. Future work must use more objective and quantifiable measures of activity and assess changes in activity levels over time. PMID- 8214237 TI - Increase in unprotected anogenital intercourse among homosexual men. AB - Results are presented from two sources, data of which indicate an increase in high-risk sexual behaviors for human immunodeficiency virus infection among homosexual men. The number of cases of gonorrhea among homosexual and bisexual visitors to municipal sexually transmitted disease clinics in Amsterdam, The Netherlands, is increasing. An increase was also observed in unprotected anogenital intercourse among homosexual participants in the Amsterdam cohort. These findings indicate that a rebound in the behavior change process among homosexual men is occurring. Furthermore, longitudinal behavioral data show that lapse and relapse into unsafe sex are prevalent in the Amsterdam cohort. PMID- 8214238 TI - HIV infection in the Women's Jail, Orange County, California, 1985 through 1991. AB - The incidence and prevalence of human immunodeficiency virus (HIV) infection among injection drug users, prostitutes, and other women seeking confidential testing in the Orange County Women's Jail were assessed from 1985 to 1991. A total of 4616 voluntary tests were completed on 3051 women, and 865 women were tested repeatedly. Eighty-two women tested positively, a ratio of 1.8 positives per 100 tests or 2.7% of all persons tested. Cumulative HIV prevalence increased from 2.5% to 2.7% between 1985 and 1991, increased by age, and showed racial differences. Of women with multiple tests, 29 seroconverted. Incidence declined from 5.7 to 1.4 cases per 100 person-years of observation between 1985 and 1991. The overall rate of seroconversion was 1.6 per 100 person-years of observation. PMID- 8214239 TI - HIV infection in hospitalized patients and Medicaid enrollees: the accuracy of medical record coding. AB - To evaluate the accuracy of computerized medical-record coding for human immunodeficiency virus (HIV), medical charts were reviewed in six sites. In 7601 hospital and 867 Medicaid records with a listed diagnosis of HIV, the predictive value for HIV was 91% or higher. HIV was identified in 34% of 1155 Medicaid records listing immune disorder or illness in the acquired immunodeficiency syndrome (AIDS) surveillance definition (without an HIV code). In hospital and Medicaid records, AIDS was identified both in records listing AIDS and records listing HIV without AIDS. HIV codes on hospital and Medicaid records were highly predictive for HIV; undercoding of HIV occurred in Medicaid records. PMID- 8214240 TI - Subjective knowledge of AIDS and use of HIV testing. AB - Increasing knowledge is an important goal of human immunodeficiency virus (HIV) prevention strategies, although increased knowledge may not be associated with increased preventive behaviors. This study examines the association of (1) objective and subjective acquired immunodeficiency syndrome (AIDS) knowledge, and (2) both objective and subjective AIDS knowledge with HIV testing use. Data are from the 1988 National Health Interview Survey. Objective and subjective knowledge were only moderately correlated. In regression analyses, higher subjective knowledge was significantly associated with higher testing use, but objective knowledge was not. The results are relevant to other preventive behaviors for which knowledge is an important factor. PMID- 8214241 TI - Behavioral outcomes of AIDS educational interventions for drug users in short term treatment. AB - This paper reports the behavioral outcomes of informational vs enhanced small group educational interventions for drug users among 407 subjects in a short-term drug treatment program. Logistic regression was used to analyze drug use and sexual behaviors at the final follow-up visit. Among lower risk subjects, the enhanced intervention was more effective in reducing injection practices that produced risks in terms of human immunodeficiency virus infection; among those at highest risk, the informational interventions were more effective. The enhanced intervention was more effective than the informational interventions in reducing cocaine use at follow-up. No differential intervention effect on sexual risk behaviors was found. PMID- 8214242 TI - The taking of free condoms in a drug abuse treatment clinic: the effects of location and posters. AB - Drug abuse treatment programs can help reduce high-risk sexual behavior in drug users by promoting condom use. This study examined the influence of distribution location and poster prompts on the taking of free condoms in a drug abuse treatment clinic. Over 6 months, condoms were available alternately, with and without poster prompts, in the clinic's private restroom or public waiting area. Overall, 381% more condoms were taken from the restroom. The presence of poster prompts did not affect condom taking. These results suggest that distribution location is a critical factor in promoting condom taking in public clinic. PMID- 8214243 TI - Preventing tap water scalds: do consumers change their preset thermostats. AB - One goal of the regulatory approach to tap water scald prevention is the installation of hot water heaters at thermostat settings considered safe. In this strategy, it is assumed that consumers will not change preset thermostat settings, an assumption evaluated in a study of 62 families. It was found that 60% of the sample did not change their preset thermostats. Surprisingly, some of those families (27%) who did not increase their settings still had unsafe (> 54 degrees C) water temperatures. PMID- 8214244 TI - AIDS and the limits of control: public health orders, quarantine, and recalcitrant behavior. AB - We undertook a survey to document the extent to which public health powers have been used to warn or restrict individuals infected with human immunodeficiency virus (HIV) whose behavior poses a risk of transmission to others. In the period from 1981 through 1990, 24 state health departments either had no mechanism for receiving reports about individuals whose behavior posed a risk of HIV transmission or took no action if they had received such reports. In states that had developed programs for dealing with such individuals, the most common response was the use of cease and desist orders. As of 1992, 10 instances of quarantine had been reported, almost all of which involved relatively brief periods of isolation. Whatever justification exists for using public health authority to confront individuals whose behavior poses a risk of HIV transmission to others, it is clear that the central focus of HIV prevention efforts must remain education, counseling, voluntary testing and partner notification, drug abuse treatment, and needle exchange programs. PMID- 8214246 TI - Mini funds, maxi impact: subcontracting injury prevention projects. PMID- 8214245 TI - Understanding AIDS: historical interpretations and the limits of biomedical individualism. AB - The popular and scientific understanding of acquired immunodeficiency syndrome (AIDS) in the United States has been shaped by successive historical constructions or paradigms of disease. In the first paradigm, AIDS was conceived of as a "gay plague," by analogy with the sudden, devastating epidemics of the past. In the second, AIDS was normalized as a chronic disease to be managed medically over the long term. By examining and extending critiques of both paradigms, it is possible to discern the emergence of an alternative paradigm of AIDS as a collective chronic infectious disease and persistent pandemic. Each of these constructions of AIDS incorporates distinct views of the etiology, prevention, pathology, and treatment of disease; each tacitly promotes different conceptions of the proper allocation of individual and social responsibility for AIDS. This paper focuses on individualistic vs collective, and biomedical vs social and historical, understandings of disease. It analyzes the use of individualism as methodology and as ideology, criticizes some basic assumptions of the biomedical model, and discusses alternative strategies for scientific research, health policy, and disease prevention. PMID- 8214247 TI - Michigan's public health program for indoor radon. PMID- 8214248 TI - Crack users' cracked lips: an additional HIV risk factor. PMID- 8214249 TI - The methodology of fatal occupational injury surveillance. PMID- 8214250 TI - Classifying unspecified and/or unexplained causes of death. PMID- 8214251 TI - Violence, injury, drugs, and maternal mortality. PMID- 8214252 TI - The availability of disaster preparation courses at US schools of public health. PMID- 8214253 TI - Germ cell neoplasms of the testis. AB - Testicular germ cell neoplasia, a disease predominantly of young men, is, for unknown reasons, increasing in incidence. Cryptorchidism, a prior testicular germ cell tumor, a family history of testicular germ cell tumors, and somatosexual ambiguity syndromes remain well-established risk factors. Intratubular germ cell neoplasia of the unclassified type represents the common precursor to the great majority of testicular germ cell tumors, and its identification in testicular biopsies reliably identifies those patients who will often progress to an invasive lesion. Seminoma appears to represent the invasive derivative of intra tubular germ cell of neoplasia of the unclassified type; problematic variants include seminomas with tubular, granulomatous, and edematous patterns. Spermatocytic seminoma is an essentially nonmetastasizing neoplasm unless complicated by the rare development of a sarcomatous component. Embryonal carcinomas usually occur admixed with other germ cell tumor types. The combination of positivity for placental alkaline phosphatase and negativity for epithelial membrane antigen can assist in the distinction of embryonal carcinomas from somatic carcinomas. The treatment of clinical stage I patients with nonseminomatous germ cell tumor with "surveillance only" may be contraindicated depending on features that include the proportion of embryonal carcinoma and the presence of lymphovascular invasion in the orchiectomy specimen. It is important to be aware that pure, mature teratomas in postpubertal patients may be associated with metastases of teratomatous or nonteratomatous type Yolk sac tumor is characterized by numerous patterns including glandular, myxomatous, sarcomatoid, hepatoid, and parietal variants. Choriocarcinomas classically have a biphasic pattern of syncytiotrophoblast and cytotrophoblast; trophoblastic proliferations lacking a biphasic pattern also occur but are difficult to classify unless this category is broadened. Mixed germ cell tumors, consisting of two or more different elements, are quite common. The polyembryoma is a distinctive, well-organized form of mixed germ cell tumor consisting of embryonal carcinoma and yolk sac tumor. PMID- 8214255 TI - Chondroid lipoma. A unique tumor simulating liposarcoma and myxoid chondrosarcoma. AB - We report 20 cases of a peculiar fatty tumor that occurred in 16 female and four male patients who were 14-70 years old (median, 36 years). Most lesions were situated in the subcutis, superficial muscular fascia, or skeletal muscle of the limbs and limb girdles (15), trunk (3), and the head and neck (2). They were 1.5 11 cm in size (median, 4 cm) and usually described as yellow (13 of 15) and encapsulated (13 of 15). Microscopically they were well circumscribed and consisted of nests, strands, and sheets of eosinophilic and vacuolated cells, which contained glycogen and fat droplets, resembling brown fat cells, lipoblasts and chondroblasts. In all cases there was a variable background of mature adipose tissue associated with a prominent, partially fibrinous to hyalinized myxoid matrix that contained acid mucopolysaccharides usually resistant to hyaluronidase digestion. Several cases had foci of serous atrophy, perivascular fibrosis, and small thrombi; two were focally calcified. The lesions stained for S100 protein (11 of 12), vimentin (10 of 11), and CD68 antigen with KP1 (9 of 11); focal staining for keratin was also seen (4 of 11), but none stained for epithelial membrane antigen or actin or with HMB45. Follow-up in 12 cases (median, 9.5 years) revealed no local recurrences or metastases. Despite its deep location and atypical cellular features, the lesion's nonaggressive behavior suggests it is benign and neither a myxoid liposarcoma nor a myxoid chondrosarcoma, with which it is most frequently confused. The presence of glycogen in vacuolated fat cells is similar to brown fat, and the presence of sulfated stromal mucins supports focal chondroid differentiation. Although the pathogenesis remains uncertain, a lipoma with hibernomatous features, myxoid change, chondroid metaplasia, and secondary degenerative features is favored over a lipogranulomatous process. PMID- 8214254 TI - Transbronchial biopsy in lymphangiomyomatosis of the lung. HMB45 for diagnosis. AB - We have investigated the presence of smooth muscle cells with immunoreactivity for melanoma-related marker HMB45 in pulmonary lymphangiomyomatosis (PLAM). Of 75 lung specimens, including a variety of lesions (obtained with both transbronchial and open lung biopsies), only PLAM (six specimens from three patients) showed the presence of HMB45-positive cells. In addition, 20 specimens of normal lung were unreactive with this monoclonal antibody. It is concluded that the smooth muscle cells of PLAM regularly exhibit a peculiar phenotype, characterized by HMB45 immunoreactivity, distinct from other smooth muscle proliferations; and the histological diagnosis of PLAM can be made when only a transbronchial biopsy is available. PMID- 8214256 TI - Proposal for standardized criteria for the diagnosis of benign, borderline, and malignant hepatocellular lesions arising in chronic advanced liver disease. AB - Although current literature contains many cases of putative premalignant hepatocellular proliferations and small hepatocellular carcinomas, no consistent nomenclature and diagnostic criteria have been put forward to describe them. These nodules, which are being detected by radiographic techniques in cirrhotic livers and removed during transplantation procedures, represent a new and challenging histologic spectrum of liver pathology. In this study, a multinational panel of five liver pathologists reviewed 23 such nodules and were able to reach a consensus on the diagnostic criteria and to devise a standard nomenclature to describe the histologic lesions. We recommend that benign nodules showing little histologic difference from cirrhotic nodules be classified as regenerative or macroregenerative, and nodules with atypical features not diagnostic of carcinoma be classified as borderline. Such standardization should facilitate further study of the pathologic features and clinical behavior of these lesions. PMID- 8214257 TI - Testicular intratubular germ cell neoplasia in children and adolescents with intersex. AB - In a review of 102 cases with various intersex states, the frequency of intratubular germ cell neoplasia (IGCN) unclassified in testes of children and adolescents was 6%. It was seen in 2 of 87 cases in the prepubertal age group and 4 of 23 cases in the pubertal age group. The frequency of IGCN was 0 of 23 in androgen insensitivity syndrome (testicular feminization), 3 of 38 in gonadal dysgenesis, 1 of 12 in true hermaphroditism, 1 of 22 in male pseudohermaphroditism, and 1 of 7 in the group with multiple congenital anomalies and ambiguous genitalia. Five cases showed unilateral and one showed bilateral IGCN. Three pubertal cases had unilateral gonadoblastoma associated with IGCN. Invasive germ cell tumor was absent in all six cases. The atypical germ cells in all testes with IGCN showed immunoreactivity with placental alkaline phosphatase. Review of the literature revealed 30 prepubertal and pubertal cases with IGCN. The median age of the combined series of 36 cases with IGCN was 13 years (range 1 month to 19 years). Concomitant invasive tumor was present in 3 of 14 cases with gonadal dysgenesis and IGCN and 2 of 18 cases with androgen insensitivity and IGCN. PMID- 8214258 TI - Pancreatic (acinar) metaplasia of the gastric mucosa. Histology, ultrastructure, immunocytochemistry, and clinicopathologic correlations of 101 cases. AB - The occasional finding within the gastric mucosa of unidentified epithelial cells with morphological features closely resembling those of pancreatic acinar cells has prompted us to investigate a retrospective series of 8,430 consecutive gastric biopsies and of 126 surgical specimens of gastric resection and total gastrectomy. The aims of the study were to morphologically and immunocytochemically characterize these cells, to define their actual prevalence in a large series of unselected cases, and to assess the clinicopathologic correlates of their occurrence. Pancreatic acinar-like cells characterized by abundant cytoplasm, which was acidophilic and finely granular in the apical and middle portions and basophilic in the basal compartment, have been identified in 101 cases (84 gastric biopsies and 17 gastrectomies). These cells, arranged in nests or in variably sized lobules among the gastric glands, were morphologically indistinguishable from pancreatic acinar cells, both by light and by electron microscopy. Furthermore, they were consistently immunoreactive for pancreatic lipase and trypsinogen and, in 75% of the cases, for pancreatic alpha-amylase. The appearance of these cells within the gastric mucosa was correlated significantly with chronic gastritis (p = 0.032) and with the simultaneous occurrence of intestinal and pyloric types of gastric metaplasia (p = 0.021). The findings indicate that this is a previously unrecognized pancreatic (acinar) metaplasia of the gastric mucosa, clinically and morphologically distinct from pancreatic heterotopia. PMID- 8214259 TI - Metastatic meningioma. Hemangiopericytoma or angioblastic meningioma? AB - The question of whether meningeal hemangiopericytoma is a variant of meningioma ("angioblastic meningioma") or a nosologically distinct entity remains controversial. We present the case histories of an intracranial meningioma and of a meningeal hemangiopericytoma, both of which developed extracranial metastases. The metastatic lesions in both cases were studied by electron microscopy, which demonstrated pericytomatous differentiation in one instance and meningothelial differentiation in the other. This report supports the opinion that meningeal hemangiopericytomas and meningiomas of the CNS are distinct pathological entities. PMID- 8214260 TI - Nodular regenerative hyperplasia in partial hepatectomy specimens. AB - To investigate possible associations of nodular regenerative hyperplasia (NRH) with antitumor chemotherapy, we reviewed 72 partial hepatic resections (55 with metastatic tumor, 12 hepatocellular carcinomas, and five benign neoplasms). Thirty autopsy livers from adults without malignancies served as controls. Studies included hematoxylin and eosin, reticulin, and trichrome stains and immunostaining for proliferating cell nuclear antigen (PCNA). Five of 72 livers (7%) had NRH. All five patients had received chemotherapy, one by intrahepatic artery infusion. Four had received chemotherapy 2 months or less before undergoing partial hepatectomy. These five cases represented 15% of the 33 patients who received chemotherapy. No NRH was seen in autopsy control livers. In contrast to NRH, multiple hyperplastic foci were seen in 28 of 72 livers (39%). This finding did not correlate with chemotherapy. Two of 30 control livers (7%) showed similar mild regenerative changes. In only one case of NRH was PCNA staining increased over controls. A band of PCNA-positive hepatocytes was seen adjacent to the tumor in 21 cases, suggesting that the presence of tumor may cause a local increase in PCNA expression. Mitoses in hepatocytes and assessment of the thickness of liver cell plates were more sensitive indicators of regeneration than PCNA. Vascular changes, such as sinusoidal fibrosis (11 of 72 cases), thickened hepatic arterioles (13 of 72 cases), and mild thickening of central veins (10 of 72 cases), did not correlate with NRH, hyperplastic foci, or chemotherapy. No cases of hepatoportal sclerosis were identified. PMID- 8214261 TI - Inflammatory fibroid polyp of the stomach. A special reference to an immunohistochemical profile of 42 cases. AB - Forty two cases (46 lesions) of inflammatory fibroid polyp (IFP) of the stomach were reviewed histologically and studied immunohistochemically. The paraffin sections were stained with a panel of antibodies against alpha-smooth-muscle actin, HHF-35, desmin, vimentin, lysozyme, alpha-1-antitrypsin, alpha-1 antichymotrypsin, KP1, Mac 387, S-100 protein, neuron-specific enolase, factor VIII RAg, and with Ulex europaeus agglutinin I. The lesions ranged in size from 0.3 to 3.5 cm with a mean of 1.2 cm. Forty (87.0%) IFPs occurred in the antrum, five in the gastric body, and one in the cardia. In all but two lesions, the mucosal layer was involved, and 20 (43.5%) lesions were entirely restricted to the mucosa. All 46 IFPs tested diffusely positive with vimentin. Positive reactions for alpha-smooth-muscle actin and HHF-35 were observed in 12 (26.1%) and 10 (21.7%) IFPs, respectively. Two lesions with alpha-smooth-muscle actin and one lesion with HHF-35 showed a diffuse staining. Seventeen (37.0%) lesions were focally positive for KP1, and seven (15.2%) IFPs were focally positive for Mac 387. All other antibodies and agglutinin were negative with the proliferating cells. The results of this study confirmed (a) the presence of myofibroblastic and histiocytic lines of differentiation in addition to the main fibroblastic features for the main cellular component in IFP, and (b) the heterogeneity of the immunoprofile of IFP. PMID- 8214262 TI - Cystic hamartoma of the renal pelvis. AB - We describe three hitherto undocumented cases of renal lesion in the adult age group that share a similar site and histological features. They are three adult women, with a short clinical history of pain and an abdominal mass. A partial or complete nephrectomy resulted in clinical cure. All cases showed an intrarenal multicystic mass situated adjacent to the pelvicalyceal system. These vaguely circumscribed lesions had no true capsule and blended in with the adjacent renal parenchyma. The histological appearance was distinctive and characterised by disorderly biphasic proliferation of epithelial and mesenchymal elements. The epithelial component consisted of tubules and cysts lined by cuboidal and columnar epithelium showing focal oncocytic changes. The stroma was cellular and predominantly fibroblastic with scattered bundles of smooth muscle cells. Despite extensive sampling, blastemal cells were not identified. The tubular epithelium was positive for CAM 5.2, epithelial membrane antigen, carcinoembryonic staining, and vimentin immunostaining. The stroma stained positively for vimentin and smooth muscle bundles for alpa smooth muscle actin and desmin. The cytological appearances of these lesions were benign. We propose that these are benign hamartomatous lesions arising as a result of faulty focal embryogenesis. They are distinct from well recognised lesions such as multilocular cysts, partially differentiated nephroblastomas, mesoblastic nephromas, and nephrogenic adenofibromas. PMID- 8214263 TI - Visceral myogenic tumors. A manifestation of HIV infection in children. AB - We report a primary smooth-muscle tumor of undetermined malignant potential of the liver in a child with acquired immune deficiency syndrome (AIDS). This patient represents the eighth child infected with the human immunodeficiency virus who developed a mesenchymal tumor other than Kaposi's sarcoma. All these children were younger than 10 years of age. These tumors often were histologically or clinically malignant and all but one were smooth-muscle tumors. These tumors arose exclusively in visceral organs, and the hepatobiliary, gastrointestinal, and tracheopulmonary systems were involved. Transmission of the virus occurred both vertically (in six children) and via blood transfusion (in two). Given the rarity of smooth-muscle tumors in uninfected children, the unusual frequency of these tumors suggests that immunosuppression induced by the virus permits the unregulated proliferation of a primitive mesenchymal cell disposed to myogenous differentiation, a situation not unlike that observed in the development of AIDS-related Kaposi's sarcoma in adults. PMID- 8214264 TI - Primary hepatic B-cell lymphoma in a child. AB - Lymphoma arising in the liver is uncommon in adults and rare in children. A 12 year-old boy with hepatomegaly and jaundice had a calcified intrahepatic large cell lymphoma of B-cell origin that expressed bcl-2 protein and had near tetraploid chromosome number with a t(8;14) (q24;q32) and a homogeneously staining region (HSR). This tumor, only the fourth example of primary hepatic lymphoma in a child, has the rare finding of an HSR before treatment and is the first human lymphoma with t(8;14) that expresses bcl-2 protein. In addition, the demonstration of extensive calcification in the tumor by computed tomography scan is highly unusual for lymphoma. Lymphoma must be considered in the differential diagnosis of primary liver tumors in children and adults, especially if the serum alpha-fetoprotein level is normal. PMID- 8214265 TI - Struma salpingis associated with struma ovarii. AB - We report a case of a struma salpingis, a benign teratoma consisting entirely of thyroid tissue in the fallopian tube. This 0.2-cm tumor was an incidental finding in a 44-year-old, clinically euthyroid, woman. The ipsilateral ovary showed a 0.1 cm struma ovarii, and there was a 7.0-cm mucinous cystadenoma of the contralateral ovary. To our knowledge, this is the second report of struma salpingis and the first account of concurrent thyroid tissue in both the tube and ovary. Struma salpingis probably arises from germ cells arrested in their migratory path towards the genital crest. PMID- 8214266 TI - Surgical pathology sign-out. Routine review of every case by a second pathologist. AB - This article describes a 1-year study undertaken to evaluate the cost and effectiveness of a surgical pathology quality assurance system in which a second pathologist routinely reviews (before release of the report) all surgical pathology cases requiring microscopic sections. The study included 5,397 cases. Fourteen discrepancies of potential clinical significance were detected by the second observer, for an error rate of 0.26%. Consultation with the clinical physicians involved in these cases indicated that in seven of these cases, the error would have resulted in a different clinical intervention than actually occurred. This "checker" sign-out system added an estimated $7 to the cost of each case, or $2,700 for each discrepancy of potential clinical significance. The value of the dual pathologist sign-out system as described here requires confirmation, because there is a paucity of information in the literature relating to routine surgical pathology sign-out accuracy. PMID- 8214267 TI - Inflammatory pseudotumor of the urinary bladder. PMID- 8214268 TI - Nasal lymphomas in Peru. PMID- 8214269 TI - Field trial of 1% niclosamide as a topical antipenetrant to Schistosoma mansoni cercariae. AB - A randomized, double-blind, placebo-controlled field trial of a topical antipenetrant lotion, 1% niclosamide, applied daily to the upper and lower limbs of farmers occupationally exposed to Schistosoma mansoni cercarial-infested water, was conducted in the Nile Delta to assess its safety and efficacy in preventing reinfection. Farmers aged 18-40 years were treated to cure their S. mansoni infections three months prior to the onset of the trial. Subjects were randomly assigned to receive niclosamide or placebo lotion that was self-applied daily for five months. A total of 186 subjects met the inclusion criteria and completed the trial. The exposure to schistosomal-infested water occurred during routine irrigation activities from June to November 1991. Stool specimens were evaluated monthly during and for two months following the lotion application period. The subjects applying the niclosamide lotion were comparable to those applying placebo lotion in age (mean 30 years for both), total water contact (184.5 hr versus 173.8 hr), reported lotion application compliance (88% versus 92%), and reported water contact involving skin exposure other than upper and lower limbs (23% versus 27%). The schistosomal reinfection rate was lower in the niclosamide group (53.3%) compared with the placebo lotion group (71.3%), (P < 0.02). Increased protection might be obtained with total body application for shorter, less intense, water contact exposures. PMID- 8214270 TI - Permethrin-impregnated bed nets for malaria control in northern Guatemala: epidemiologic impact and community acceptance. AB - Permethrin-impregnated bed nets were evaluated as a control measure for malaria in northern Guatemala. Twelve hundred forty participants were allocated to one of three experimental groups (impregnated bed nets [IBN], untreated bed nets [UBN], and controls) and followed up for a period of 13 months. The incidence density of malaria was significantly lower in both IBN (86 cases/1,000 person-years) and UBN groups (106/1,000) compared with that in controls (200/1,000). No difference in malaria incidence was noted between the IBN and UBN groups. Complaints of fever and chills were less frequent in the IBN group compared with controls. The participants were enthusiastic about the nets, which they saw as a means for avoiding nuisance insects more than for preventing malaria. Most (85%) wanted to wash their nets every 4-12 weeks, a practice known to shorten the duration of residual insecticide action. Larger studies are needed to determine whether or not impregnated bed nets offer an advantage over untreated nets in this setting. PMID- 8214271 TI - Anopheles hermsi, probable vector of malaria in New Mexico. AB - Samples of Anopheles freeborni s.1. were collected from areas of New Mexico where malaria had once been common and sporozoites had been isolated from this species. Specimens were identified by analysis of polytene chromosome banding patterns and by specific rDNA fragments generated through the polymerase chain reaction. All samples collected in New Mexico were identified as An. hermsi, which was the probable vector of malaria in this region during the early 20th century. PMID- 8214272 TI - A new focus of scrub typhus in tropical Australia. AB - A new focus of scrub typhus (Rickettsia tsutsugamushi) is described in a remote rain forest region of the Northern Territory of Australia. Five serologically confirmed cases, two near fatal with multisystem involvement, have occurred since the area became accessible to tourists. As tourism increases, other remote foci of vectors and organisms may also be recognized in tropical Australia. PMID- 8214273 TI - Ciguatera on Kauai: investigation of factors associated with severity of illness. AB - Epidemiologic characterization of ciguatera fish poisoning has been limited by lack of laboratory confirmation, absence of prospective follow-up, and incomplete analysis of age-related factors. A 1985 outbreak on the island of Kauai in the state of Hawaii that involved 15 persons of various ages was investigated to determine factors associated with disease severity. The presence of ciguatoxin was detected in leftover portions of the implicated fish by enzyme immunoassay. All cases were medically and epidemiologically investigated and followed prospectively. Ten of the 15 cases demonstrated bradycardia; seven were hospitalized, including two requiring placement in intensive care. Bradycardia was associated with increasing age and body weight (P < 0.01 and < 0.05, respectively) as well as the amount of toxic fish consumed (P < 0.01). Duration of illness ranged from two to 132 days. Increasing duration of illness was correlated with both increasing age and weight (rs = 0.64 and rs = 0.72, respectively, both P < 0.01) and was independent of amount and components of toxic fish consumed. The correlation between increasing age and weight with duration and severity of symptoms may be explained by prior subclinical toxin exposure and is consistent with the observation that repeated ciguatoxin exposures are associated with more severe illness. The association between amount of toxic fish consumed and bradycardia is consistent with an increased dose of ciguatoxin. The findings of this outbreak investigation support previously unconfirmed observations. PMID- 8214274 TI - Increased serum phospholipase A2 activity in Malawian children with falciparum malaria. AB - Some clinical manifestations of severe malaria resemble those of sepsis and there may be mediators of the host response that are common to both sepsis and malaria. Phospholipase A2 (PLA2), a proinflammatory enzyme whose expression is induced by tumor necrosis factor (TNF), has been implicated in the pathogenesis of complications of the sepsis syndrome. We examined levels of circulating PLA2 in Plasmodium falciparum malaria and studied the association of PLA2 with disease severity. Plasma PLA2 and TNF were measured in 75 Malawian children with P. falciparum malaria. The mean (SD) plasma PLA2 activity in children with acute malaria was 53,804 (37,256) units/ml as compared with 424 (349) units/ml in 34 healthy controls (P < 0.00001). The mean PLA2 activity in 45 convalescent patients was 2,546 (7,372) units/ml (P < 0.00001). In 48 patients with pretreatment PLA2 activity less than 60,000 units/ml, mortality was 8.3%, while in 27 patients with pretreatment PLA2 levels greater than 60,000 units/ml, mortality was 33.3% (P = 0.008). There were significant correlations between PLA2 and TNF (r = 0.471, P < 0.01), density of parasitemia (r = 0.443, P < 0.0001) and a decrease in hematocrit (r = 0.352, P < 0.005). These data show that P. falciparum malaria is associated with a markedly increased circulating PLA2, especially in patients with severe disease, as manifested by high parasite burden, anemia, coma, and death. PMID- 8214275 TI - Chloroquine bioassay using malaria microcultures. AB - The in vitro microculture technique was used to develop a relatively simple bioassay for estimating chloroquine (CQ) in plasma or serum. Chloroquine concentrations were determined by multiplying the maximum inhibitory dilution of plasma/serum required to inhibit growth of the CQ-sensitive FC27 isolate of Plasmodium falciparum by the minimum inhibitory concentration of CQ against the same isolate. Human serum samples spiked with CQ gave similar measurements using both bioassay and high-performance liquid chromatography. The antimalarial activity of plasma or serum samples collected from 13 patients treated with CQ was equivalent to the sum of the combined activity of CQ and its metabolite, mono desethylchloroquine. The concentration of these components using the bioassay could be expressed conveniently in terms of CQ concentration equivalents. This bioassay can be used to estimate drug concentrations without the use of sophisticated methods or equipment. Since it is based on the microculture technique, it can be easily carried out in conjunction with the drug susceptibility test to assess CQ treatment failures in malaria patients. PMID- 8214276 TI - Predictors of treatment failure in multiple drug-resistant falciparum malaria: results from a 42-day follow-up of 224 patients in eastern Thailand. AB - We report here the results of a 42-day follow-up of 224 patients treated with mefloquine for uncomplicated falciparum malaria in Eastern Thailand. The risk of treatment failure among the 209 patients who completed the follow-up was 57% (95% confidence interval [CI] = 50,64). The daily risk of treatment failure, estimated through an exponential survival function, was constant during the follow-up period and equal to 1.9%. Five patient characteristics were found to be independent and important predictors of treatment failure in a Cox proportional hazards model: a young age (adjusted hazard ratio [AHR] for an increase of 10 years of age = 0.75 [95% CI = 0.62, 0.90]); a history of at least three documented mefloquine treatments in the past year (AHR = 1.89 [95% CI = 1.10, 3.24]); a parasitemia count > 100,000/microliter (AHR = 1.80 [95% CI = 1.16, 2.80]); and a history of diarrhea in the first two days after treatment (AHR = 1.51 [95% CI = 0.99, 2.31]). A hemoglobin level < or = 10 g/dl on the day of consultation was also a predictor of treatment failure, but only among patients who had been treated for malaria in the past 120 days (AHR = 4.38 [95% CI = 1.55, 12.1]). These latter patients may have become anemic while they were unsuccessfully treated with mefloquine for an infection by a multiple drug resistant strain in the past 120 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214277 TI - Causal prophylactic and radical curative activity of WR182393 (a guanylhydrazone) against Plasmodium cynomolgi in Macaca mulatta. AB - Primaquine is the only currently available drug effective against persistent tissue stages of relapsing malaria in humans. Causal prophylactic and radical curative properties of WR182393 (a guanylhydrazone) were investigated as part of an effort to evaluate alternatives to primaquine in the rhesus monkey (Macaca mulatta)/Plasmodium cynomolgi test model. The drug was suspended in dimethylsulfoxide for intramuscular (im) injection. A pilot study indicated causal prophylactic activity in a regimen of 40 mg base/kg/day im for three days beginning the day before intravenous challenge with 1 x 10(6) P. cynomolgi sporozoites. Regimens of 31, 10, 3.1, and 0 mg base/kg/day im for three days were then tested in groups of two monkeys given a similar challenge. The two animals given 31 mg base/kg/day remained parasite-free. Average time to parasitemia for the lower dosage groups was 38, 18, and 8 days respectively. Groups of two monkeys with sporozoite-induced P. cynomolgi infections were also treated for seven days with 31, 10, 3.1, and 0 mg base/kg/day im in combination with 10 mg base/kg/day of chloroquine orally. Both monkeys given 31 mg base/kg/day did not relapse. The average time to relapse following treatment was 48, 29, and 8 days, respectively, for the lower dosage groups. Compound WR182393 is the first non-8 aminoquinoline class of drug to exhibit both causal prophylactic and radical curative properties against a relapsing primate, vivax-like malaria. PMID- 8214278 TI - Response of Plasmodium vivax variants to chloroquine as determined by microscopy and quantitative polymerase chain reaction. AB - Genotypic heterogeneity in the repetitive portion of the circumsporozoite (CS) protein of Plasmodium vivax has been reported from many P. vivax-endemic areas. The objective of this study was to determine if the VK210 and VK247 CS variants of P. vivax differed in their clearance rates following chloroquine (CQ) therapy. One hundred seventy-one cases of P. vivax infection occurring in patients presenting to a research treatment center in Thailand were analyzed. Finger-prick blood samples were collected for microscopy and spotted onto filter paper at presentation and on each of five days of observation through supervised CQ therapy. A portion of the CS gene was amplified from filter paper samples by the polymerase chain reaction (PCR) and genotyped by oligoprobes specific for the VK210 and VK247 CS repeat regions. The mean time to clear parasitemia as determined by thick blood smear was significantly longer for pure VK210 infections (51 hr; 95% confidence interval [CI] 47.4-54, P = 0.006) and mixed infections (53 hr; 95% CI 49.2-56.7, P = 0.0009) as compared with VK247 infections (44 hr; 95% CI 39.8-47.9). Five patients matched for parasitemia, age, sex, and previous malaria experience were selected from each of the three genotype groups in the larger study for further analysis by quantitative PCR of P. vivax genotype-specific DNA during a treatment course. The mean time to clear parasite DNA, as determined by PCR, was significantly slower for VK210 parasites (65 hr; 95% CI 51-79) than for VK247 parasites (47 hr; 95% CI 30-63, P = 0.045).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214279 TI - Morphologic effects of artemisinin in Plasmodium falciparum. AB - Ultrastructural changes induced in Plasmodium falciparum by artemisinin were studied in vitro. Electron microscopic autoradiography was performed on infected erythrocytes that were exposed in vitro to 3H-dihydroartemisinin and 14C artemisinin. These drugs consistently were located in food vacuoles and mitochondria. Two hours after administration, changes were observed in parasite mitochondria, rough endoplasmic reticulum, and nuclear envelope. At four hours, in addition to the earlier changes, nuclear membranes and, to a lesser extent, some plasma membranes formed myelin figures. In addition, there was a disappearance of ribosomes, and a destruction of food vacuole membranes. These changes may lead to the total disorganization of the parasites. Approximately 30% of the parasites manifested these alterations. PMID- 8214281 TI - Immunization against porcine cysticercosis in an endemic area in Mexico: a field and laboratory study. AB - An antigenic extract from Taenia solium metacestodes was evaluated for immunogenicity in pig populations from a large area of endemic porcine cysticercosis in the State of Guerrero, Mexico. A total of 3,295 pigs from 18 villages were immunized with a single dose of 250 micrograms of protein administered intramuscularly. Systematic immunization was also performed on pigs (1,076 immunizations) from two of the villages with the highest percentages of cysticercosis. A year after immunization, porcine cysticercosis decreased from 4.8% and 5.4% to 0%. Immunity against the T. solium metacestode was estimated in vitro by measurements of 3H-thymidine uptake and inhibition of leukocyte migration. Peripheral blood lymphocytes from immunized cysticercotic (pigs that had cysticercosis prior to immunization), cysticercotic immunized (pigs that acquired cysticercosis after immunization), and normal control pigs incorporated 3H-thymidine better than lymphocytes from cysticercotic pigs when stimulated with concanavalin A. A significant inhibition in the leukocyte migration inhibition test was also found in leukocytes from immunized cysticercotic pigs (P < 0.01). Histopathologic studies revealed granuloma formation surrounding the metacestodes of the immunized cysticercotic and cysticercotic immunized pigs. These metacestodes exhibited several stages of destruction. Large numbers of eosinophils were frequently observed in a close association with the degeneration and destruction of parasites. Metacestodes in control cysticercotic pigs were intact and surrounded by a minor inflammatory reaction. Finally, the rate of in vitro evagination of scolices was high in metacestodes obtained from cysticercotic pigs and low or absent in those from immunized pigs (P < 0.01). PMID- 8214280 TI - Characterization of a circulating antigen involved in immune complexes in visceral leishmaniasis patients. AB - Complications of visceral leishmaniasis are explained in part by immune complex pathology, particularly nephritis. Using the polyethylene glycol precipitation method, we identified among these complexes a Leishmania infantum circulating antigen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Monoclonal antibodies were produced to specifically detect this antigen. This protein (molecular weight 51 kD) is a cytoplasmic antigen of L. infantum and its synthesis by promastigotes is related to stationary-phase culture. It was present in sera from dogs whose leishmaniasis was associated with nephritis, and it was found in the sera of 30% of human patients with visceral leishmaniasis. It was also detected in the sera of patients with cutaneous leishmaniasis, and it persists in the sera of clinically cured subjects. PMID- 8214282 TI - Sequestration pattern of parasitized erythrocytes in cerebrum, mid-brain, and cerebellum of Plasmodium coatneyi-infected rhesus monkeys (Macaca mulatta). AB - Six rhesus monkeys (Macaca mulatta) infected with Plasmodium coatneyi were studied for parasitized red blood cell (PRBC) sequestration in microvessels of the brain. The degree of PRBC sequestration is different in the cerebral, mid brain, and cerebellar microvessels, with sequestration occurring preferentially in the cerebellum. This pattern resembles that of PRBC sequestration in cerebral and cerebellar microvessels in human falciparum malaria. The morphologic appearance of sequestered cells under light and electron microscopy as well as the PRBC sequestration pattern bolsters the contention that the rhesus monkey infected with P. coatneyi is an appropriate primate model for the experimental study of human cerebral malaria. PMID- 8214283 TI - Identification of single specimens of the Anopheles gambiae complex by the polymerase chain reaction. AB - A ribosomal DNA-polymerase chain reaction (PCR) method has been developed for species identification of individuals of the five most widespread members of the Anopheles gambiae complex, a group of morphologically indistinguishable sibling mosquito species that includes the major vectors of malaria in Africa. The method, which is based on species-specific nucleotide sequences in the ribosomal DNA intergenic spacers, may be used to identify both species and interspecies hybrids, regardless of life stage, using either extracted DNA or fragments of a specimen. Intact portions of a mosquito as small as an egg or the segment of one leg may be placed directly into the PCR mixture for amplification and analysis. The method uses a cocktail of five 20-base oligonucleotides to identify An. gambiae, An. arabiensis, An. quadriannnulatus, and either An. melas in western Africa or An. melas in eastern and southern Africa. PMID- 8214284 TI - Hayes Martin Lecture. Less can mean more. PMID- 8214285 TI - Influence of prior radiotherapy on the development of postoperative complications and success of free tissue transfers in head and neck cancer reconstruction. AB - The purpose of this study was to determine whether prior radiotherapy had any effect on the development of postoperative complications in patients undergoing microvascular tissue transfers for reconstruction of head and neck cancer. A prospective database was used to review 354 consecutive patients who had a total of 368 free tissue transfers limited to the head and neck during the 4-year period from July 1988 to June 1992. Postoperative complications in 167 patients who received preoperative radiotherapy (XRT) were compared with those of 187 patients who did not undergo radiotherapy preoperatively (NR). No statistical differences in complications or flap loss between the two groups were noted using the chi 2 test or Fisher's exact test (p > 0.2). Total flap loss occurred in 5.3% of the XRT group (9 of 169) and 5.0% of the NR patient group (10 of 199), and partial flap loss occurred in 4.1% of the irradiated patients and 2.5% of the nonirradiated patients. Major wound complications requiring additional surgery occurred in 16% of the XRT group and 11% of the NR group. Minor wound complications that did not require further surgery occurred in 21% of the irradiated patients and 18% of the nonirradiated patients. No significant difference in the timing or dose of preoperative radiation, previous neck dissection, or anastomotic type could be documented in failed versus successful flaps (two-tailed t-test, p > 0.80, and chi 2, p > 0.2). Our results show that, in a large group of cancer patients undergoing free tissue transfers to the head and neck, prior radiotherapy or surgery did not predispose them to a higher rate of acute flap loss or wound complications than their nonirradiated cohorts. PMID- 8214286 TI - Lobectomy versus total thyroidectomy for differentiated carcinoma of the thyroid: a matched-pair analysis. AB - The extent of surgical resection for differentiated carcinoma of the thyroid gland confined to one lobe remains controversial. Although primary tumor size and extrathyroid extension are associated with a poor prognosis, the presence of multifocal lesions is not associated with an adverse prognosis. Therefore, the role of lobectomy versus total thyroidectomy must be studied in a prospective, randomized trial. Due to the need for long-term follow-up, such a trial has not yet been undertaken. As an alternative to such a trial, we have identified 146 patients from a consecutive series of 931 previously untreated patients undergoing surgical treatment at 1 institution between 1930 and 1980. For this study of matched-pair analysis, 73 patients, aged 45 years or older, were matched in each arm for significant prognostic factors. One group underwent lobectomy, and the other group underwent total thyroidectomy. The 20-year survival rate in the lobectomy group was 82% compared with 73% in the total thyroidectomy group (p = not significant). The patterns of failure in these two groups of patients were examined. A comparison of the patients who underwent lobectomy with an unmatched group of patients who underwent lobectomy showed similar survival rates. On the other hand, unmatched patients undergoing total thyroidectomy had a poorer survival rate than the matched group. This signifies a more aggressive nature of disease in the unmatched group of patients undergoing total thyroidectomy. We therefore conclude that low-risk patients undergoing lobectomy are likely to do as well as those undergoing total thyroidectomy and without the increased risk of the morbidity of total thyroidectomy. PMID- 8214287 TI - Transoral-transpharyngeal approach to the upper cervical vertebrae. AB - The classical operative approaches to the cervical spine include the posterior one and the anterior exposure along the sternomastoid muscle. However, neither of these are helpful in exposing the upper cervical vertebrae, especially the odontoid process, atlas, and axis. We have used the transoral-transpharyngeal exposure for lesions of the odontoid process and upper (first to third) cervical vertebrae in six patients. The pathologic processes included rheumatoid disease and fracture of the cervical vertebrae, suspected tumor with compression of the spinal cord, basilar invagination, and compression of the medulla. In all six patients, the exposure was excellent, and postoperative morbidity was minimal. Tracheostomy was performed routinely in all these patients. In five patients, vertebral stabilization was performed as a secondary procedure a few days after the initial anterior decompressive surgery. The transoral-transpharyngeal approach appears to be relatively easy. It is associated with minimal complications and provides excellent exposure of the odontoid and upper cervical vertebrae for a microneurosurgical approach. Modifications of this approach include incision of the soft palate, excision of a portion of the hard palate, and, occasionally, transmandibular median labio-mandibulo-glossotomy (Trotter's) approach. Although the technique was described initially approximately 35 years ago, this neglected anatomic approach will facilitate cooperative efforts between head and neck surgeons and neurosurgeons. PMID- 8214288 TI - Osseous free flaps for orbit and midface reconstruction. AB - Osseous free flaps were used for reconstruction of the orbit and midface in 10 patients. The reconstruction was done at the time of tumor resection in two patients (20%) and secondarily in eight patients (80%). Nine patients (90%) had previously received radiotherapy. The flaps used were fibula (four), radial forearm (two), scapula (two), and split iliac crest (two). Flap loss occurred in one patient. Complications occurred in 2 of 10 (20%) patients. The results were classified as good in seven patients, fair in two, and poor in one. The patient classified as having a poor result was the one who sustained the flap loss; he refused further surgery. Reconstruction was directed to the maxilla in five patients, the orbit in two, and both in three. The radial forearm flap was best used for orbit-only reconstruction because of the small amount of bone required. The fibula, iliac crest, and scapula were best used for larger defects involving the maxilla. Osseointegrated dental implants were used successfully in three patients. Osseous free flaps are indicated for midface reconstruction when bony support is needed and previous irradiation prevents the use of nonvascularized grafts. PMID- 8214289 TI - Ultrasound-guided fine-needle aspiration biopsy in the management of thyroid disease. AB - During a 23-month period, 59 patients were referred for ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) of the thyroid gland because of inadequate orthodox (office) FNAB, a clinically small lesion, or an occult lesion. Seventy percent of the group (41 patients) was referred for surgery, which revealed cancer in 37% of patients, adenoma in 19%, and benign disease in 44%. US-guided FNAB yielded false-positive reports in 0% of patients, false-negative reports in 5% to 12%, and inadequate aspirates in 32%. The US-guided FNAB technique had a sensitivity of 60% to 90%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 80%, and an accuracy of 85%. US-guided FNAB provides cytologic information in 60% of patients in whom a diagnosis cannot be established by orthodox (office) means, thus enhancing the diagnostic ability of clinicians who can recommend a treatment program with confidence. PMID- 8214290 TI - Importance of repeat fine-needle biopsy in the management of thyroid nodules. AB - Fine-needle aspiration (FNA) biopsy of a thyroid nodule was performed in 797 patients. Ninety-six patients had resection of the thyroid nodule performed subsequent to a one-time FNA biopsy. The surgical pathology of these 96 cases demonstrated a 5.8% false-negative rate and a 9.9% false-positive rate. As a consequence, we prospectively evaluated the routine practice of repeat FNA of cytologically benign thyroid nodules. Repeat FNA confirmed the original benign cytology in 183 (93%) of 196 patients. Seventeen of these 183 patients with benign FNA on both biopsies had resection of the nodule performed because of the development of suspicious clinical signs or in response to the patient's choice; 1 recurrent cyst was found to be carcinomatous. Of the 13 patients demonstrating a change in cytology on repeat FNA biopsy, 9 had a nodule that was classified as possibly malignant (suspicious); 6 of these patients underwent resection, and 1 patient was found to have a carcinomatous nodule. Four patients had nodules that were classified as probably malignant on repeat FNA biopsy; all of their nodules were resected, and three of them were found to be carcinomatous. This study demonstrates that, although one-time FNA biopsy of thyroid nodules is highly accurate, with a relatively low false-negative rate, repeat fine-needle biopsy improves on this diagnostic accuracy, thereby decreasing the risk of misdiagnosing a thyroid nodule that is malignant. PMID- 8214291 TI - Influence of fine-needle aspiration biopsy and frozen section examination on the management of thyroid cancer. AB - In order to delineate the influence of fine-needle aspiration biopsy (FNAB) and frozen section examination (FS) on the management of patients with thyroid cancer, a review of 310 patients with thyroid cancer, seen in follow-up during a 3-year period, was completed. Combined FNAB and FS examination were assessed in 225 patients, 172 (76%) with papillary carcinoma, 36 (16%) with follicular carcinoma, 13 (6%) with Hurthle cell carcinoma, and 4 (2%) with medullary carcinoma. The diagnosis according to FNAB was malignant in 78 patients (35%), cellular in 135 (60%), and benign in 12 (5%). All 78 patients with a malignant FNAB diagnosis had papillary cancer. The results of FS examination correlated with the FNAB findings in 74 patients (95%), whereas 4 patients (5%) had a false negative FS diagnosis of "adenoma." Of the 135 patients with a cellular FNAB diagnosis, FS examination showed cancer in 75 (56%): 58 with papillary carcinoma, 7 with follicular carcinoma, and 10 with Hurthle cell carcinoma. Sixty patients (44%), 30 with papillary carcinoma, 27 with follicular carcinoma, and 3 with Hurthle cell carcinoma, had a cellular FNAB diagnosis and a FS diagnosis of a follicular neoplasm. Twelve patients (5%), 6 with papillary carcinoma, 4 with medullary carcinoma, and 2 with follicular carcinoma, had both false-negative FNAB and FS. From these results, we conclude that FS examination is indicated for intraoperative decision-making in patients with a cellular FNAB diagnosis but is unnecessary when the FNAB diagnosis is either benign or malignant. In order to avoid possible reoperation, near-total thyroidectomy should be presented as an alternative for the treatment of a hypofunctioning thyroid nodule when both FNAB and FS results are consistent with "follicular neoplasm." PMID- 8214292 TI - Parathyroid localization: inability to predict multiple gland involvement. AB - Preoperative localization using various imaging techniques can accurately predict the location of solitary parathyroid adenomas in about 75% of patients. Its value has been questioned because of the high success rate of parathyroid exploration without localization. The ability of localization studies to differentiate preoperatively between patients with solitary adenomas and those with multiple gland disease would be valuable because bilateral exploration might be avoided in many cases. Ultrasonography, thallium-201/technetium-99m subtraction scintigraphy, and magnetic resonance imaging were used to evaluate 16 patients with primary hyperparathyroidism who were ultimately found at surgery to have multiple enlarged parathyroid glands. No single imaging technique was able to identify more than 53% of enlarged glands, and only four patients were accurately predicted preoperatively to have enlargement of multiple parathyroid glands. Existing imaging techniques cannot be relied on to predict multiple gland involvement preoperatively. Bilateral surgical exploration is mandatory in all patients with primary hyperparathyroidism. PMID- 8214293 TI - Improved survival in the treatment of squamous carcinoma of the oral tongue. AB - During the past 15 years, newer trends in the management of oral tongue cancer have included increased use of elective neck dissection and mandible-sparing procedures, as well as a commitment to postoperative radiotherapy in patients with stage III and IV tumors. We retrospectively reviewed the records of 297 consecutive patients who underwent primary treatment of a squamous cancer of the oral tongue at our institution between 1978 and 1987 to determine the effects of the aforementioned therapeutic approaches on patients' survival. Determinate 5 year survival was 65% overall (82% for stages I and II, 49% for stages III and IV), which represents a significant improvement when compared with the survival rates we reported for the preceding 10-year period, despite the fact that the distribution of patients according to stage was about the same. Some type of lymphadenectomy was performed in 130 patients, 63 of whom underwent elective node dissection for T1 or T2 lesions. Forty-one percent of the latter had positive nodes, which upstaged the disease in a significant proportion of N0 patients. The number of positive nodes (more than two positive nodes) was a significant predictor of survival (p = 0.03). Postoperative radiotherapy was performed in 70% of patients with stage III or IV tumors. In this group of patients, the incidence of neck recurrence was reduced (13% versus 29% for patients who did not receive radiotherapy). The only long-term survivors among patients with stage IV tumors were those who received postoperative radiotherapy. Our results strongly suggest that the improvement in results is related to a more aggressive and effective treatment of the neck. PMID- 8214294 TI - Differential oncogenic expression in thyroid follicular and Hurthle cell carcinomas. AB - Although Hurthle cell tumors are considered to be variants of follicular neoplasms, they have distinct cytologic and behavioral characteristics. To elucidate the basis for these differences, the expression of 5 oncogenes and growth factors (Pan-ras, N-myc, transforming growth factor-alpha [TGF-alpha], transforming growth factor-beta [TGF-beta], and insulin-like growth factor 1 [IGF 1]) was compared between 12 follicular carcinomas and 8 Hurthle cell carcinomas by immunocytochemistry. The percentage of follicular carcinomas and Hurthle cell carcinomas that stained positively for the different oncogenes was as follows and respectively: Pan-ras 8% versus 63%; TGF-alpha 17% versus 63%; TGF-beta 25% versus 88%; IGF-1 17% versus 88%; and N-myc 17% versus 100%. All these differences were highly significant by the chi 2 test. This difference in the expression of oncogenes between Hurthle cell carcinomas and follicular carcinomas suggests that these two tumors could, in fact, represent separate entities. PMID- 8214295 TI - Prospective comparison of technetium-99m-sestamibi/iodine-123 radionuclide scan versus high-resolution ultrasonography for the preoperative localization of abnormal parathyroid glands in patients with previously unoperated primary hyperparathyroidism. AB - Surgery for primary hyperparathyroidism is successful in 95% of patients, but ectopic glands and anatomic variations in location are causes of surgical failure. The radionuclide imaging agent, technetium (Tc)-99m-sestamibi, in conjunction with subtraction iodine-123 scanning, is a new method of preoperative localization of abnormal parathyroid glands. In a study approved by the Institutional Review Board, 22 patients with primary hyperparathyroidism underwent preoperative evaluation with high-resolution ultrasonography and Tc-99m sestamibi/I-123 radionuclide scanning for attempted localization of abnormal parathyroid glands. Results of Tc-99m-sestamibi scanning and ultrasound were correlated with surgical and pathologic findings. Of 22 patients, 16 had a solitary parathyroid adenoma, 1 had a double adenoma, and 5 had diffuse parathyroid hyperplasia. The Tc-99m-sestamibi/I-123 radionuclide scan preoperatively identified a solitary adenoma in 14 of 16 patients (sensitivity: 88%). However, when the data were analyzed retrospectively along with surgical and pathologic findings, the Tc-99m-sestamibi scan correctly localized all parathyroid adenomas for a sensitivity of 100%. The one patient with a double adenoma had a localization image consistent with two enlarged glands. All patients with diffuse parathyroid hyperplasia had Tc-99m-sestamibi imaging consistent with diffuse hyperplasia, although delineation of individual enlarged glands was not possible. High-resolution ultrasound identified 11 of 16 parathyroid adenomas (sensitivity: 69%). The patient with a double adenoma had a negative ultrasound. Ultrasound was less accurate in five patients with diffuse hyperplasia: one scan was completely negative, two scans revealed only one enlarged gland, and two scans revealed two enlarged glands. The Tc-99m sestamibi/I-123 subtraction radionuclide scan is more sensitive than high resolution ultrasonography for the preoperative localization of abnormal parathyroid glands. Tc-99m-sestamibi/I-123 radionuclide scanning may be more useful than ultrasonography to the surgeon in the preoperative localization of abnormal parathyroid glands. PMID- 8214296 TI - End results of 114 extended "commando" operations for retromolar trigone carcinoma. AB - Retromolar trigone carcinomas invade the mandible and the pterygoid and/or masseter muscles in a large number of cases. There is also a significant risk of ipsilateral lymph node neck metastasis. The purpose of this retrospective study was to report the survival results of 114 consecutive patients who underwent an extended "commando" operation (retromolar operation) from 1960 to 1991. The technique is a variation of a composite resection. The operation consists of hemimandibulectomy with resection of the pterygoid and masseter muscles, with an ipsilateral neck dissection (radical classical, modified, or supraomohyoid). The oral cavity and oropharyngeal defects were closed primarily in 83 patients. In the remaining 31 patients (27.2%), it was reconstructed by a tongue flap (12 patients), pectoralis major myocutaneous flap (10 patients), and other flaps (9 patients). There were 104 men and 10 women, with a median age of 55 years. All patients had squamous cell carcinoma. Tumor stages were T1 (5 patients), T2 (44 patients), T3 (24 patients), T4 (28 patients), and Tx (13 patients). The metastases were predominantly in levels I and II. Only patients with positive nodes at levels I and/or II had histologically positive nodes at levels IV or V. Complications occurred in 51.8% of the patients (wound infection in 21 patients, 18.4%). Sixty-six patients underwent postoperative irradiation (4 to 70 Gy, median: 50 Gy). To date, 41 patients have presented with 50 tumor recurrences: 31 local, 9 in the dissected neck, 3 in the contralateral neck, and 7 distant. The 5 year actuarial overall survival rate was 80.0% in patients with T1 tumors, 57.8% in those with T2 tumors, 46.5% in those with T3 tumors, and 65.2% in those with T4 tumors. In conclusion, the retromolar operation can be performed with acceptable morbidity, and it is effective (5-year overall survival rate of 55.3%). The rate of local recurrences (27.2%) suggests that radiotherapy as an adjunctive modality should be indicated in patients in whom recurrences are likely. PMID- 8214297 TI - Management of occult neck metastases in oral cavity squamous carcinoma. AB - A large experience with patients who had radical neck dissection for oral squamous carcinoma has been reviewed in order to compare elective lymphadenectomy results with those achieved when neck dissection was delayed until metastases appeared or was performed initially for limited N1 neck disease. No significant difference in survival rates was observed, but neck failure was a more significant problem when treatment was delayed. This was most obvious in patients treated for tongue cancer. Although the impact of elective neck treatment on "cure" rates will require prospective studies, it seems clear that elective lymphadenectomy can enhance regional control of cancer and improve the quality of the patients' survival. PMID- 8214298 TI - Surgical management of squamous cell carcinoma of the base of the tongue. AB - An 11-year experience with 100 patients who had surgery as definitive treatment for squamous cell carcinoma of the base of the tongue between 1979 and 1989 has been retrospectively reviewed. Although 81% of the patients had stage III or stage IV disease, mandible continuity was maintained in 86%, and the larynx was preserved in 80%. Lymphadenectomy was performed in conjunction with the primary resection in a total of 89 patients, including 62 patients who had clinically evident metastases. Postoperative radiation was administered to 63 patients because of positive resection margins (17), positive cervical lymph nodes (34), or high tumor stage (12). Overall and disease-specific 5-year survival rates for the entire group were 55% and 65%, respectively. The 5-year disease-specific survival rates for stages I/II, III, and IV were 77%, 64%, and 59%, respectively. Local control was achieved in all but 18 patients. Our results indicate that surgery remains a viable treatment option for patients with advanced base-of tongue cancer. Prospective trials are necessary to compare surgery versus definitive radiotherapy with respect to patients' survival and quality of life. PMID- 8214299 TI - Contribution of serum inhibitory factors and immune cellular defects to the depressed cell-mediated immunity in patients with head and neck cancer. AB - The immune system of patients with head and neck cancer is frequently depressed. Serum inhibitory factors and immune cell dysfunction are known contributors to this depression, but their relative roles are unclear. We have examined these factors to determine whether a common pathway is involved. Is the defect an unresponding "switched-off cell" or is it a remedial defect responsive to the removal of serum inhibitory factors and/or to lymphokine restoration? Immune tests were performed in 66 patients with high-stage head and neck cancer. Serum inhibitory factors were measured by incubation of heat-inactivated serum (10%) with phytohemagglutinin (PHA)-stimulated lymphocytes or natural killer (NK) cells using the K562 assay. Lymphokine-activated killer (LAK) cell cytotoxicity was measured (in the presence/absence of serum) using chromium 51-labeled Raji tumor cells cultured 5 days with interleukin-2 (IL-2) (100 or 1,000 U/mL) and/or interferon-alpha (INF-alpha) (100 U/mL). IL-2 receptors, CD25 or p55 (low affinity) and p75 (high affinity), were measured by flow cytometry through fluorescence-activated cell sorter analysis. Serum inhibitory factors were detected in more than 50% of the patients. Head and neck cancer sera significantly inhibiting the normal lymphocyte response to PHA (11 of 22 patients), as well as significantly inhibiting the NK response of normal lymphocytes and the functional expression of the IL-2 receptor. LAK cell function at low-dose IL-2 was depressed in 45% of the patients (9 of 20) and was restored by increased IL-2 (1,000 U/mL) or a combination of IL-2 and INF-alpha. Twenty five percent of the patients were unresponsive to maximum lymphokine stimulation. Half of the patients had depressed expression of the low-affinity IL-2 receptor (CD25). The cause of immune depression in patients with head and neck cancer is multifactorial and is related to serum inhibitory factors, as well as to inherent cellular defects. Based on these data, we would suggest a therapeutic approach in selected patients that includes the removal of serum inhibitory factors by plasmapheresis and restoration of cellular defects by combined IL-2 with or without INF-alpha. PMID- 8214300 TI - Posterior triangle metastases of squamous cell carcinoma of the upper aerodigestive tract. AB - The trend toward function-conserving surgery in the treatment of squamous cell carcinoma of the head and neck has led to a progression from radical neck dissection to modified neck dissection and selective neck dissection has growing support. These surgical modifications have resulted from an effort to spare structures uninvolved with malignancy. Level V dissection can be associated with spinal accessory dysfunction in some patients even when the nerve remains intact. In this study, we have attempted to address the need for level V dissection by determining the prevalence of level V metastases in a large series of patients undergoing radical neck dissection. There were 1,123 patients who underwent 1,277 neck dissections between 1965 and 1986. A review of pathologic and clinical records revealed 40 patients (3%) with positive nodes at level V. The prevalence of level V metastases was greatest with hypopharynx and oropharynx primary tumors (7% and 6%, respectively). Level V metastases were found in 1% of patients with oral cancers and 2% of those with larynx cancers. Groups were divided into N0 (282), N+ (719), and subsequent N+ (276), depending on the clinical status at the time of surgery. Thirty-seven of 40 patients with posterior triangle metastases were clinically N+. The prevalence of metastases at level V was 1% for N0, 5% for N+, and 0% for subsequent N+. This large series shows minimal involvement of metastases at level V. The low likelihood of metastases at level V, even in N+ disease, should be considered when performing lymphadenectomy for squamous cell carcinoma of the upper aerodigestive tract. PMID- 8214301 TI - Selective jugular node dissection in patients with squamous carcinoma of the larynx or pharynx. AB - We reviewed our experience with 66 patients who had 85 jugular node dissections (JND) between 1984 and 1991. When JND was used as a staging procedure in 56 patients with N0 squamous carcinoma of the larynx or hypopharynx, it identified 15 of 19 patients (79%) who had occult metastases. The pattern of neck failure in six patients after JND strongly suggests that the dissection must be carried posterior to the internal jugular vein in order to achieve adequate sampling. Neck failure was a relatively minor problem in this patient population, and the indications for elective JND may be less than compelling in most patients with N0 class laryngeal or pharyngeal squamous carcinomas. Our very limited experience with JND for resection of N1 disease supports a growing consensus that limited lymphadenectomy and aggressive radiotherapy may yield comparable results in carefully selected patients with palpable metastases. Obviously, these are issues that can only be resolved by prospective, randomized studies. PMID- 8214302 TI - Benign lymphoepithelial lesions of the parotid. AB - Persistent generalized lymphadenopathy has been well described in patients with seropositivity to the human immunodeficiency virus (HIV). Moreover, isolated enlargement of the parotid gland and parotid lymphadenopathy have been noted much more frequently over the past few years. Histologically, these lesions demonstrate follicular hyperplasia, cystic dilatation of the ducts lined by pseudo-stratified squamous epithelium, and lymphocytic infiltrates. They are generally considered to be benign lymphoepithelial lesions of the parotid or hyperplastic periparotid lymph nodes. The relationship of this entity to the AIDS related complex (ARC) and the subsequent development of AIDS is not clear. Over the past 7 years, we have seen 50 patients with parotid enlargement in whom the diagnosis of benign lymphoepithelial lesion was made. Fine-needle aspiration was performed in 32 patients. Although not conclusively diagnostic, needle aspirates ruled out primary salivary glandular pathology. Most patients gave a history of intravenous drug abuse. HIV tests have been performed on a routine basis only in the last 2 years, and these were positive in the majority of the patients. Thirty five patients underwent surgical excision. In the initial 20 patients, we routinely performed parotid exploration, identification of the facial nerve, and superficial parotidectomy. In the last 15 patients, we changed our surgical approach to parotid exploration and excision of the mass in the tail of the parotid. The exposure of the posterior belly of the digastric muscle, with identification and removal of the deep jugular node, has become routine. In each case, we found an enlarged lymph node in the deep jugular region, which was not clinically palpable preoperatively. The rate of surgical complications was minimal, and, after resection of the mass, patients improved symptomatically. If the patient shows obvious signs of AIDS, a nonsurgical approach with repeated aspirations should be considered, and treatment with zidovudine offered. PMID- 8214303 TI - Prevention of Frey's syndrome with superficial musculoaponeurotic system interposition. AB - Frey's syndrome after parotidectomy has an incidence generally reported to be 50% to 60% and is thought to be due to aberrant reinnervation of sweat glands by postganglionic parasympathetic fibers normally supplying the parotid gland. One hundred twelve patients had interposition of a flap of the superficial musculoaponeurotic system between the parotid bed and the overlying skin. Only one patient developed symptomatic Frey's syndrome, and one other patient had positive results on starch iodine testing. In patients not having the interposition, the incidence of symptomatic Frey's syndrome and positive starch iodine testing was 83% and 87%, respectively. PMID- 8214304 TI - Mandible preservation with oral cavity carcinoma: rim mandibulectomy versus sagittal mandibulectomy. AB - Rim mandibulectomy, a mandibular-preserving procedure, has proven to be a successful method of treating squamous cell carcinoma with limited mandibular involvement. The operation involves resection of the occlusal rim of the mandible. Using strain gauge techniques, we investigated how much bone should remain at the rim mandibulectomy site. Maintenance of a 1-cm-thick segment of bone inferiorly is required to reduce the risk of fracture formation. In comparing the relative strength of the different mandibular preservation techniques, the rim mandibulectomy was found to be more resistant to fracturing than was lingual sagittal mandibulectomy. PMID- 8214305 TI - A-O reconstruction plate and sternal osteomyocutaneous flap in primary mandibular reconstruction. AB - Mandibular arch reconstruction remains a functional and aesthetic challenge for the head and neck surgeon. The recent popularity of vascularized free composite flaps has made them a first choice for many surgeons. However, the increased operating time, high failure rate, frequent need for operative rescue, specialized postoperative care and facilities, and specialized training required to perform them have prompted many extirpative surgeons to attempt other techniques or to leave the mandible unreconstructed. Six sternal osteomyocutaneous flaps, a variant of the familiar pectoralis major myocutaneous flap, were utilized to reconstruct mandibular defects of up to 10 cm in patients undergoing composite resection for cancer, with or without preoperative radiotherapy. The use of the A-O reconstructive plate to secure the bony portion of the flap to the unresected mandible has considerably simplified and speeded the procedure over external fixation as originally described. When both soft tissue and bone are required to rehabilitate the operative defect, the sternal osteomyocutaneous flap has proven to be a reliable and time-effective procedure. PMID- 8214306 TI - Face and neck neurogenic neoplasms. AB - Surgeons should be aware that any mass in the region of the cranial nerves, brachial plexus, cervical sympathetic plexus, or a major peripheral nerve can be of neurogenic origin. Solitary neurogenic tumors of the head and neck can simulate metastatic masses or congenital lesions. If they are resected unrecognized and/or without regard to their nerve origin, major and permanent nerve defects can unnecessarily occur. Thirty-two patients, 16 males and 16 females, ranging in age from 5 to 69 years, had 33 extracranial solitary neurogenic neoplasms resected. The nerves involved were the cervical sympathetic plexus in 7 patients, branchial plexus in 6, spinal accessory nerve in 5, vagus nerve in 4, hypoglossal nerve in 3, facial nerve in 2, and 6 other nerves in 1 patient each. The technique is to dissect out the neurilemoma without destroying the nerve sheath or nerve trunk. Despite careful dissection, the four patients with masses of the vagus nerve had permanent ipsilateral cord paralysis. PMID- 8214307 TI - Accuracy of frozen section in the evaluation of salivary tumors. AB - The records of 333 patients who underwent surgery were reviewed to document the accuracy of frozen section in the evaluation of salivary gland tumors. Frozen sections were obtained in 310 patients. The final pathologic diagnoses included 210 benign tumors and 45 malignancies. The sensitivity for the detection of malignancy was 69%, and the specificity was 96%. The specific accuracy to correctly identify the type of malignancy present was only 51%. In four patients, a false-positive diagnosis of malignancy was made. Frozen section was much more accurate in the evaluation of benign salivary tumors. Forty-three of 45 Warthin's tumors were correctly identified by frozen section. Two tumors thought to be Warthin's tumors on frozen section proved to be low-grade mucoepidermoid carcinomas. One tumor reported to be a benign mixed tumor was actually a malignant mixed tumor. In this series of patients, frozen section proved to be no more accurate in the evaluation of salivary tumors than what has been reported in the literature for fine-needle aspiration biopsy. PMID- 8214308 TI - Thyroid carcinoma presenting as an enlarged cervical lymph node. AB - Differentiated thyroid cancer most commonly presents as a thyroid nodule. Cervical node metastases are commonly observed. In the present report, we describe the clinical presentation, pathologic findings, surgical approach, and follow-up of 43 patients in whom the initial presentation of thyroid cancer was that of an enlarged cervical lymph node. At surgery, 65% of the patients had additional lymph node involvement. The thyroid pathology was papillary carcinoma in all patients, and, in two thirds of patients, the thyroid primary was 1 cm or smaller in size. Forty patients underwent thyroidectomy and modified neck dissection; 3 were treated by thyroidectomy alone. One patient died of disease, 7 were lost to follow-up after 4 to 27 years, 5 died of unrelated causes, and the remaining 30 are alive and free of disease 1.5 to 33.5 years after surgery (mean: 14.8 years). PMID- 8214309 TI - Comparative evaluation of fixation methods after mandibulotomy for oropharyngeal tumors. AB - Mandibulotomy for gaining access to the posterior aspect of the oral cavity and oropharynx for excision of tumors has been widely employed for several decades. However, the technical aspects of the procedure continue to evolve. This study compares the complications and bony union rates in a consecutive series of 135 patients undergoing mandibulotomy at 1 institution between 1987 and 1991, using wires and miniplates. The primary tumor sites were oral cavity in 35 patients, oropharynx in 98, and deep lobe of the parotid gland in 2. Twenty-eight patients were previously irradiated, and 62 received postoperative radiotherapy. Thirty eight patients had a straight-line osteotomy, 31 had step osteotomy, and 66 had notched osteotomy. The fixation of the osteotomy site was done with wires in 59 patients and miniplates and screws in 76 patients. The duration of follow-up ranged from 1 to 5 years. No difference in complications or bony union was observed in patients who underwent repair with wires or miniplates. Due to the number of surgeons and their preferences for different types of osteotomies, as well as the differences in surgical techniques, we further studied the 2 methods of fixation employed by 1 surgeon who performed notched osteotomies on all of his patients (56 patients). Twenty-two underwent repair with wires, and 34 with miniplates. Four patients with wires and seven with miniplates developed wound complications requiring removal of wires in two and miniplates in one. Delayed union or nonunion was not observed in any patient. Fixation with wires or miniplates is equally satisfactory as long as adequate immobilization of the mandibular segments is achieved. PMID- 8214310 TI - Composite resection with mandibulectomy in the treatment of posterolateral oral cavity and lateral oropharynx squamous cell carcinoma. AB - From 1972 to 1987, 403 patients underwent a composite resection consisting of segmental mandibulectomy and neck dissection for the treatment of bucco-pharynx squamous cell carcinoma (303 patients had postoperative radiotherapy [XRT], 29 patients had preoperative XRT, and 100 patients had tissue salvage performed after XRT). Of the 303 patients who received preoperative XRT, 32 were clinically staged T2, 149 were staged T3, and 122 were staged T4; 194 of the 303 patients were staged N0. In the 100 patients who experienced relapse and who required "salvage surgery," the restaging found 20 patients staged T2, 39 staged T3, and 41 staged T4; 73 of the 100 patients were staged N0. The patients' mean postoperative stay was 15 days for those who had prior surgery and 21 days for those who had salvage surgery. With a minimum follow-up of 5 years, locoregional recurrences and postoperative death occurred in 86 of 274 patients (31%) in whom surgery and postoperative XRT were performed; in 17 of 29 patients (59%) who had preoperative XRT performed; and in 61 of 100 patients (61%) who had salvage surgery performed. In addition, in terms of functional results, only 61% of patients (206) were able to maintain normal speech function, and only 23% (91) were able to maintain normal oral feeding. Of the 403 patients, the 5-year survival rates were 33% for the overall population, 42% for patients with postoperative XRT, 16% for patients in whom operation was performed after preoperative XRT, and 17% for patients who underwent salvage surgery. PMID- 8214311 TI - Laparoscopic monopolar electrosurgery. PMID- 8214312 TI - PEG/PEJ and the incidence of aspiration. PMID- 8214313 TI - Paragangliomas of the temporal bone. AB - Recent advances in diagnosis and surgical therapy of glomus tumors of the temporal bone have been made. These advances make it possible for surgeons to benefit patients affected by this locally aggressive and morbid tumor. More sensitive diagnostic modalities and a physician alertness make early surgical cure a possibility. Careful planning and observation of basic surgical principles help to minimize morbidity and improve functional results. PMID- 8214314 TI - Clinical review of olfaction. PMID- 8214316 TI - Inverted follicular keratosis. PMID- 8214315 TI - Closure of tracheocutaneous fistula using a modified cutaneous Z-plasty. PMID- 8214317 TI - Successful treatment of zygomycosis of the paranasal sinuses with surgical debridement and amphotericin B colloidal dispersion. PMID- 8214318 TI - Endoscopic debulking of a pituitary tumor. PMID- 8214319 TI - Selected problems treated by vocal fold injection of collagen. AB - INTRODUCTION: This study evaluates the results of vocal fold injection of bovine collagen. METHODS: A group of patients were selected because they were not good candidates for other forms of treatment. This included patients with scarred vocal folds, bilateral vocal fold pathology with a small glottic gap, and unilateral vocal fold pathology with atrophy. Assessment used patient self evaluation, perceptual judgments of voice recordings, laboratory data based on acoustic signal analysis, and aerodynamic measures during voice production. Vocal folds were also studied by videostroboscopy. RESULTS: Most of the 45 patients treated with collagen injection were helped. In some cases, the improvement was marginal but documented using a variety of measures. Significant improvement was noted in jitter (P = .002), shimmer (P = .002), and maximum intensity (P = .026). There were no major complications and no hypersensitivity reaction. CONCLUSION: This study demonstrates the potential usefulness of collagen injection in the treatment of a selected group of patients with glottic insufficiency who are not good candidates for other forms of therapy. Objective analysis of results suggest improved function in this difficult to treat patient population. Further clinical investigation is warranted. PMID- 8214320 TI - Propofol for maintenance of general anesthesia: a technique to limit blood loss during endoscopic sinus surgery. AB - PURPOSE: Most cases of endoscopic sinus surgery are amenable to techniques using local anesthesia with monitored sedation. However, it is frequently the preference of the patient to have surgery under general anesthesia. One major drawback of general anesthesia is the increased bleeding encountered which can interfere with optimal visualization of the intranasal anatomy. In this study, an analysis was made to see if technique of general anesthesia has an impact on estimated blood loss in patients undergoing endoscopic sinus surgery. METHODS: Twenty-five patients undergoing outpatient endoscopic sinus surgery under general anesthesia over a 1-year period were reviewed retrospectively to determine if anesthetic technique had an impact on estimated blood loss. Twelve patients were identified who received a continuous intravenous infusion of the nonbarbituate hypnotic agent propofol as the primary anesthetic agent, and 13 patients were identified who received anesthesia based on inhalational isoflurane. RESULTS: There was no difference between the duration of surgery or the intraoperative mean arterial blood pressure when comparing the two groups. The average estimated blood loss in the propofol group was 101 mL compared with an average estimated blood loss of 251 mL in the isoflurane group (P < .01). CONCLUSIONS: General anesthesia based on propofol infusion may have the advantage of decreased bleeding compared with conventional inhalation agents, making endoscopic sinus surgery technically easier and safer by improving endoscopic visualization of the surgical field. This anesthetic technique may have other applications in otolaryngology, where bleeding within a confined space frequently can interfere with visibility. PMID- 8214321 TI - Recommendations for therapy of head and neck cutaneous melanoma. AB - PURPOSE: The essential element in the treatment of a primary cutaneous malignant melanoma is an adequate definitive excision. The breadth and depth of such excisions and the appropriateness of a prophylactic neck dissection, however, remain a source of controversy. METHOD: A review of our experiences with 500 patients with head and neck malignant melanoma treated in our clinic between 1967 and 1987 is presented. RESULTS AND CONCLUSIONS: The thickness of the lesion, the factor that correlated most closely with potential for metastatic development, can be used as a guide for determining the extent of excision and the appropriateness of elective node dissection. Wide excision of invasive lesions varies in their margins from 1 cm for lesions that measure less than .75 mm in thickness to 3 cm if the melanomas measure greater than .75 mm or show ulcerations or have a scalp localization. Prophylactic neck dissection is necessary for lesions between .75 and 1.5 mm in thickness, whereas in tumors with a depth of invasion greater than 1.5 mm the outcome of the disease is not improved by prophylactic neck dissection. PMID- 8214322 TI - Tubeless anesthetic technique for optimal carbon dioxide laser surgery of the larynx. AB - PURPOSE: To evaluate the operative conditions and safety of a tubeless technique of anesthesia for carbon dioxide laser surgery of the larynx. MATERIALS AND METHODS: This prospective study evaluated 78 consecutive procedures in 72 adult patients undergoing carbon dioxide laser microlaryngeal surgery. Anesthesia was maintained by an intravenous infusion of Propofol (ICI Pharmaceuticals, Cheshire, UK) while the patient breathed spontaneously without endotracheal intubation. RESULTS: The operative conditions were optimal in 76 of the 78 procedures providing a clear uninterrupted view of the larynx with no combustible material in the surgical field. CONCLUSIONS: This series shows the technique described to be safe without risk of combustion and provides an unobstructed view to the larynx. PMID- 8214324 TI - The influence of elective neck dissection on neck relapse in NO supraglottic carcinoma. AB - INTRODUCTION: Mortality due to cancer in patients treated for squamous cell carcinoma of the supraglottic larynx is closely associated with regional relapse in the neck. Controversy exists relative to the most effective way to manage potential cervical metastases. METHODS: The records of 126 patients with carcinoma of the larynx treated between 1975 and 1986 were reviewed. Sixty-three patients with T2-4,NO squamous cell carcinoma of the supraglottic larynx are the subject of this report. Twenty-one patients underwent surgical resection of the primary tumor plus elective neck dissection while 42 patients underwent surgical resection of the primary tumor without neck dissection. Subsequent relapse in the neck was ascertained. RESULTS: The overall neck relapse rate was 31.7%. In patients treated with neck dissection, the relapse rate was 14.3%, while relapse in the patients who did not have neck dissection was 40.5%. Radiation therapy did not seem to make a significant difference in relapse rate in this patient population. CONCLUSIONS: We conclude that elective neck dissection decreases the neck relapse rates significantly in patients treated for NO supraglottic carcinoma. PMID- 8214323 TI - Anticardiolipin antibody-induced sudden profound sensorineural hearing loss. AB - INTRODUCTION: A link between sensorineural hearing loss (SNHL) and autoimmune disease is postulated. The association of SNHL in a patient with systemic lupus erythematosus is reported. METHODS: An adolescent female with left lateral medullary syndrome and right internuclear ophthalmoplegia was diagnosed with systemic lupus erythematosus. Treatment with prednisolone markedly improved her symptoms. Two years later, profound SNHL developed in the right ear. Extensive serologic testing was undertaken. RESULTS: Serologic tests for syphilis were false-positive. Enzyme-linked immunosorbent assay to the immunoglobulin (Ig)G anticardiolipin antibody was positive. The anticardiolipin antibody is strongly correlated with episodes of recurrent venous or arterial thrombosis. CONCLUSIONS: It appears that the anticardiolipin antibody may be associated with sudden profound sensorineural hearing loss in patients with autoimmune disease. PMID- 8214325 TI - Computed tomographic evaluation of otosclerosis. PMID- 8214326 TI - Changes in nasal resonance secondary to adenotonsillectomy. PMID- 8214327 TI - Mitochondrial dysfunction in Rett syndrome. An ultrastructural and biochemical study. AB - We report the ultrastructural and biochemical alterations of muscle mitochondria in two girls with Rett syndrome. Our findings suggest the presence of an energy metabolism impairment the primary or secondary role of which in the pathogenesis of this syndrome cannot be defined at present. PMID- 8214328 TI - Cerebral magnetic resonance spectroscopy in Rett syndrome. Failure to detect mitochondrial disorder. AB - A total of eight girls with Rett syndrome were examined, by 31phosphorous magnetic resonance spectroscopy (31P MRS) (4 girls), proton MRS (1H MRS) (4 girls), muscle biopsying (2 girls), and determination of pyruvate and lactate in plasma (5 girls), to investigate the hypothesis of a mitochondrial malfunction as the etiology for this neurologic disorder. Almost all examinations, including electron microscopy in search of structural mitochondrial abnormalities, gave normal results, the only exception being the not unexpected finding of slight neurogenic atrophy in the muscle biopsy specimen from a 15-year-old girl. PMID- 8214329 TI - An epidemiological survey of severely mentally and physically disabled children in Okinawa. AB - A survey of severely mentally and physically disabled children (SDC) aged 6-15 years was conducted in Okinawa. There were a total of 170 SDC on 1 May 1989, the prevalence rate being 0.89/1,000. The prevalence rate of SDC over the last 20 years has shown a decreasing trend, which seems to be associated with the decreased incidence of cerebral palsy (CP) in the latter half of the 1970s and the first half of the 1980s. Furthermore, CP accounted for the largest percentage (51.8%) of underlying disorders or conditions of SDC, similar to 20 years ago. This suggests that the incidence of CP could be an important factor in the prevalence of SDC. In addition, the percentages of SDC with CP with profound mental impairment and epilepsy, 97.7% and 79.5%, respectively, were larger than 20 years ago. This suggests that SDC with CP who have severe associated impairments have increased. PMID- 8214330 TI - Two siblings with partial trisomy 1(q42.3-ter). AB - Two brothers, aged 6 and 4 years, with an unbalanced chromosome translocation (partial trisomy 1), and their mother, a balanced carrier of the translocation, t(1;3)(q42.3;p26.3), were described. Both patients show minor anomalies; a large head with a prominent forehead, low-set and soaring ears, a high-arched palate, a shallow nasal bridge, hypertelorism, and slender hands and feet. The manifestations in our cases were very mild compared to in the previously reported cases of partial trisomy 1. And our patients exhibit psychomotor retardation and ventricular dilatation on brain CT. We speculated that the amount of extra material reflects the phenotype. Our cases and previous reports indicate that the minimum clinical features of partial trisomy 1 are poor psychomotor development, a prominent forehead, and slender hands and feet. And many cases have macrocephaly with ventricular dilatation or hydrocephalus. So these features may be a key for the diagnosis of very mild partial trisomy 1. PMID- 8214331 TI - Chronic subdural hematoma, as an initial manifestation of glutaric aciduria type 1. AB - A 10-month-old male with glutaric aciduria type-1 (GA-1) is reported. This patient showed frequent partial motor seizures, irritability, and involuntary movements, including oral dyskinesia at the age of 3 months. On admission, magnetic resonance (MR) scanning revealed a chronic subdural hematoma and widening of the bilateral insular cisterns. Urine organic acid analysis showed marked excretion of glutaric acid, 3-hydroxy glutaric acid and glutaconic acid, suggesting GA-1. Removal of the subdural hematoma was effective for the irritability but not for the extrapyramidal signs. This is the first report of a subdural hematoma as an initial symptom in a patient with GA-1. However, the complication of subdural fluid collection in GA-1 is not rare. To our knowledge, of 29 patients with GA-1 who underwent computed tomographic or MR scans, 5 had subdural fluid collection. Disproportional hypoplasia of the temporal lobes may be a suggestive etiology of subdural fluid collection/chronic subdural hematoma. PMID- 8214332 TI - A case of Isaacs syndrome with high CSF protein and a large cisterna magna. AB - An 11-year-old boy exhibited continuous muscle fiber activity. He had suffered from stiffness of his hands, difficulty in relaxing his hands after gripping, and making skilled movements with his fingers. His clinical symptoms improved after treatment with carbamazepine. Electromyography (EMG) showed that he had continuous electrical discharges both at rest and during sleep. These discharges completely disappeared after the peripheral nerve was blocked with Lidocaine. An evoked electromyogram showed suppression of abnormal discharges after the F response. These electrophysiological findings indicated that the disorder originated in the spinal anterior horn cells. CT scanning showed a large cisterna magna in the posterior cranial fossa. Protein in the cerebrospinal fluid was elevated. PMID- 8214333 TI - A case of early infantile epileptic encephalopathy (EIEE) with anatomical cerebral asymmetry and myoclonus. AB - The authors report a case of early encephalopathy with myoclonus, tonic spasms and a suppression-burst pattern on electroencephalography (EEG) associated with unilateral cerebral hypertrophy following hemiatrophy. This patient showed frequent myoclonus in relation to a suppression-burst pattern resembling that in early myoclonic encephalopathy (EME). Moreover, the case also showed tonic spasms, from the age of 13 days, in series, as seen in Ohtahara syndrome. On the other hand, there was a previously undescribed peculiar CT scan finding, which showed hypertrophy of the right cerebral hemisphere at birth, following hemiatrophy. Neuropathological examination revealed cerebral atrophy associated with heterotopia and an ependymal hyperplasia in the right hemisphere, suggesting hemimegalencephaly. This case should be classified as Ohtahara syndrome accompanied by myoclonus, because of the spasms in series interrupting the suppression-burst pattern, and the etiological factor of brain malformation. The nosological aspects of this epileptic encephalopathy are discussed. PMID- 8214334 TI - Chronological SPECT studies of a patient with subacute sclerosing panencephalitis. AB - We describe here chronological single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) of a patient with subacute sclerosing panencephalitis (SSPE) from the early clinical stages. The case, an 8 year-old Japanese girl, was in clinical stage I of the disease on admission. A SPECT study with 99mTc-hexamethylprophyleamine oxime (99mTc-HM PAO) and 123I-IMP revealed hypoperfusion of cerebral blood flow in the bilateral occipital areas and a part of the cerebellum. Initially, no abnormal findings were observed on CT and MRI. Subsequently, however, MRI indicated abnormal signal intensity dominantly in the area of the occipital white matter where hypoperfusion of cerebral blood flow was found by the initial SPECT studies. This abnormal cerebral hypoperfusion appeared to improve after treatment with oral inosiplex and intrathecal interferon-alpha over 6 months of the clinical course. The abnormal signal intensity on the MRI also decreased, but simultaneous cranial CT demonstrated diffuse cortical atrophy and slight ventricular dilatation. PMID- 8214335 TI - Computed tomography and magnetic resonance imaging of affected muscle in childhood acid alpha-glucosidase deficiency: a case report. AB - A 13-year-old boy with the juvenile type of acid alpha-glucosidase deficiency is presented. Muscle CT scans performed before muscle biopsy revealed high image density over the entire rectus femoris, and partial high density over the iliopsoas, adductor magnus and tibialis anterior. MRI of the rectus femoris in the transaxial plane showed high image intensity over the entire length of the muscle in both T1- and T2-weighted images. A biopsy revealed a surprising histological difference between the rectus femoris, which showed pronounced vacuolar myopathy with excessive glycogen, and the vastus lateralis, in which deposition of glycogen was minimal and the CT image indicated a normal muscle density. The findings in this case suggest that CT scanning and MRI are useful in recognizing muscle involvement in acid alpha-glucosidase deficiency, which is characterized by images of increased density compared to normal muscle, presumably because excessive deposition of glycogen and lysosomal membranes cause high X-ray absorption on CT and high signal intensity on MRI. PMID- 8214336 TI - Two possible cases of Alexander disease. Multimodal evoked potentials and MRI. AB - We describe two unrelated girls with slowly progressive leukodystrophy with macrocephaly. On MRI, both patients exhibited diffuse involvement of the cerebral white matter, excluding the internal capsule and optic radiation. Their visual evoked potentials were normal. Short-latency somatosensory-evoked potentials exhibited the absence of early scalp components. Auditory brainstem responses in both patients showed intramedullary conduction disturbance. These MRI and electrophysiological findings are similar to those in infantile Alexander disease. PMID- 8214337 TI - Urinary excretion of N-acetyl-beta-glucosaminidase and beta-galactosidase by patients with epilepsy. AB - In an effort to detect active renal tubular dysfunction in 74 epileptic patients being treated with antiepileptic drugs (AEDs), we measured the urinary activity of two lysosomal enzymes, N-acetyl-beta-glucosaminidase (NAG) and beta galactosidase (beta-gal). The heterogeneity of the types of seizures and therapeutic regimens permitted us to examine the potential differences in AED effects. We also examined the chronological changes in the urinary excretion rates of NAG and beta-gal in 132 healthy controls, aged 3 months to 37 years. Increased NAG excretion rates (defined as > or = 2 S.D. compared with age-matched controls) were found in 36.5% of the patients. Valproic acid was highly associated with this increase, and in combination with potassium bromide caused the highest levels of NAG excretion. Among the patients taking carbamazepine, only 11.1% exhibited high levels of NAG in urine. Children under 1 year of age showed higher levels of NAG excretion than older patients. In spite of the abnormally high urinary excretion of NAG, we could not detect any signs of renal dysfunction by urinalysis and measurement of blood urea nitrogen and serum electrolytes. We cannot exclude the possibility that the increased levels of urinary NAG in epileptic patients might be due to renal tubular enzyme induction by AEDs. PMID- 8214338 TI - Simultaneous EEG-VTR and transverse topographical analyses of absence seizures in children. Some prognostic implications. AB - The clinical symptoms and electroencephalographic (EEG) features of typical absence seizures, including transverse topographical analysis (TTA), were studied retrospectively using a simultaneous EEG-VTR system in 36 children aged between 3 and 17 years. Complex absences were more common than simple, and oral automatisms were the most frequent complex symptoms. Occurrence of complex symptoms was directly proportional to the length of seizures. There was no association between lateral TTA type and simple absences. Prognosis was favorable in patients with long seizure duration (P < 0.01), bilaterally synchronous monomorphic spike-waves throughout the seizure discharges (BSMTSD) (P < 0.005) and lateral TTA type (P < 0.05). Two different mechanisms of origin for BSMTSD/non-BSMTSD and lateral/non lateral TTA types are probably responsible for the difference in prognosis. Favorable prognosis in patients with long seizures is discussed in relation to the duration of the illness. EEGs with BSMTSD and lateral TTA type may indicate a favorable prognosis in children with absence seizures. PMID- 8214339 TI - Regional cerebral blood flow in diagnosis of childhood onset partial epilepsy. AB - We compared regional cerebral blood flow assessed by [123I]N-isopropyl-p iodoamphetamine (IMP) single-photon emission tomography (SPECT) with magnetic resonance imaging (MRI), computed tomography (CT) and interictal surface electroencephalography (EEG) to evaluate its diagnostic potential in 24 patients with partial seizures with onset in childhood. Focal low uptake areas were observed on SPECT scans of 18 patients and were presumed to represent epileptogenic areas in 17. MRI revealed an abnormality in 12 and CT in 6 patients, and all organic lesions showed SPECT abnormalities, too. Six patients without focal structural abnormalities showed regional perfusion deficit on SPECT. Routine scalp EEG revealed an epileptic focus in 17 patients and three of them showed discordant results between SPECT and EEG, which suggested more serious brain disorders. In two patients without EEG localization only SPECT showed focal abnormalities in the probable epileptic area. [123I]IMP-SPECT was useful in locating the epileptic focus, particularly during the early period after the onset of partial seizures when the EEG gave inconclusive results. PMID- 8214340 TI - Learning disorders and delinquency. AB - Learning disorders of various types are relatively common, and the reaction of the affected child can lead to social problems. The higher the children's intelligence the more frustrated they can become. Lack of self-esteem can cause unacceptable behaviour in trying to counteract this, and boost the child's confidence. There is evidence that learning disabilities are prevalent among those who are delinquent. Theories suggest this may be due directly to the learning difficulties, or to failure at school, starting a series of events leading to delinquency, or to the idea that those with learning difficulties are treated differently, especially when it comes to legal proceedings. Epilepsy can easily lead to learning disorders; particularly if the temporal lobes are involved, there are associated emotional disorders, or side effects of treatment. Also this association is often found amongst children with attention deficit disorders. If the link between learning disorders and delinquency is recognised there is considerable scope for prevention. PMID- 8214341 TI - Long latency event-related potentials (P300) in gifted children. AB - In children, P3 latency decreases with increasing age. This decrease could be linked with the maturation of cognitive processes. According to this hypothesis, event-related potentials P3 were recording in gifted children to research an electrophysiological correlation with the mental precocity. Auditory long latency event-related potentials were recorded in 10 gifted children (IQs over 140) and 23 control subjects. The part of variance related to age was extracted by comparing deviations from regression line as a function of age. Stimulus-evoked N1 component latency was not statistically different in the two populations. Event-related P3 component latency was significantly shorter in the gifted children at Cz (P < 0.05). Inter-peak interval N1-P3 was significantly shorter at all three recording sites (P < 0.01 at Fz and CZ, P < 0.02 at Pz). These results suggest a relationship between the P3 component and cognitive ability in children. PMID- 8214342 TI - Chorea as a presentation of herpes simplex encephalitis relapse. AB - Three infants, ages 3 months to 3 years, presented with chorea as the initial manifestation of herpes simplex encephalitis (HSE) relapse. Patient 2, treated with repeated 10 day courses of 30 mg/kg/day of acyclovir, had no clear improvement in neurological status. Patient 1, treated with a repeated 10-day course, improved only to have another HSE relapse 4 years later. Patient 3 clearly improved soon after a 3-week course of acyclovir at conventional dosages. A fourth patient (Patient 4) who relapsed with chorea after what was thought to be HSE, and who did not respond to repeated acyclovir treatment, was negative for herpes simplex virus indicators on brain biopsy and DNA testing. We recommend treating all patients suffering from HSE with a minimum 3-week course of acyclovir at 30-35 mg/kg/day in 3 divided doses. PMID- 8214344 TI - Epidemiology of acute childhood encephalitis. Aichi Prefecture, Japan, 1984-90. AB - The case records for 256 patients with acute encephalitis, including meningoencephalitis, acute encephalopathy and Reye syndrome, were obtained from 36 departments of pediatrics in large hospitals through questionnaires which were sent in 1990-92. The incidence rate per 100,000 child years was 3.3, and was more frequent in children aged 0-4 years (rate 6.6) than 5-15 years (rate 2.0), with statistical significance. The disease in the 105 etiologically diagnosed patients was due to measles virus (24), herpes simplex (21), rubella (24), and other agents (36), including two cases of human herpesvirus 6. A third of the infants with measles encephalitis were first seen at less than 18 months of age. Eighteen cases of rubella encephalitis occurred during an epidemic of rubella in Aichi Prefecture, 1987-88. The short-term outcome (mean length of follow-up: 2 years 3 months) of encephalitis was death in 20 cases (7.8%) and sequelae in 58 (24%). Eleven patients died within 7 days and five by the 8-14th day from onset. Thirty six children had multiple residual impairments, including twelve who were severely handicapped. The prognosis for both life and sequelae was significantly poor for herpes simplex encephalitis in etiologically diagnosed patients. We stress the importance of an increase in the vaccination rate and the establishment of an early diagnostic system. PMID- 8214343 TI - Fukuyama-type congenital muscular dystrophy and the Walker-Warburg syndrome. AB - We compared the neuropathological findings in two cases of the Walker-Warburg syndrome (WWS) with those in 6 of Fukuyama-type congenital muscular dystrophy (FCMD). Remarkable differences were noticed between the two conditions. The central nervous system (CNS) dysplasia in WWS, which involved diffuse agyria and hydrocephalus, was more severe than that in FCMD. In WWS the septum pellucidum was absent, and the corpus callosum, basal ganglia and thalami were markedly hypoplastic. The cerebellum was severely hypoplastic and the vermis was partly absent. The pyramidal tracts could not be identified. On the other hand, the general configuration of the CNS was well preserved in FCMD. The cerebral cortices exhibited diffuse or focal micropolygyria with or without a few pachygyric lesions, but the severity was variable. The cerebellum was not hypoplastic, but exhibited focal micropolygyria. The pyramidal tracts were aberrant. WWS and FCMD, however, did not show any distinct differences on microscopic analysis of the cerebral cortices. There was leptomeningeal glio mesenchymal overgrowth, and the horizontal lamination of the nerve cells was distorted throughout by proliferating gliovascular bundles or septa. We found in this study that the CNS pathology in WWS was compatible with type II lissencephaly, and thus differed from that in FCMD. Hypoplasia of the cerebellum and a partial absence of the vermis also seemed to be predominant features of WWS, which can be used to differentiate WWS from FCMD. In this study, we concluded that FCMD and WWS are different disease entities because they differ in their clinical manifestations, including eye lesions and CNS pathology, and because no familial concomitance of FCMD and WWS has been reported. PMID- 8214345 TI - Magnetic resonance signal intensity ratio of gray/white matter in children. Quantitative assessment in developing brain. AB - Magnetic resonance imaging (MRI) findings in 87 children with various clinical entities were used to determine the signal intensity ratio of gray/white matter in T1- and T2-weighted images using a 1.5 T MR Scanner. Signal intensity ratio changes in both T1- and T2-weighted images correlated well with advancing age (y = 0.9349-0.001575, r = -0.584, P < 0.0001 in T1-weighted images; y = 0.9798 + 0.002854, r = 0.723, P < 0.0001 in T2-weighted images), but the correlation was more linear when we included only normally developed (34) children (y = 0.9689 0.001967, r = -0.654, P < 0.0001 in T1-weighted images; y = 0.9882 + 0.002965, r = 0.747, P < 0.0001 in T2-weighted images). Abnormal ratios were observed in patients with congenital hydrocephalus, inherited metabolic diseases and cerebral palsy. Although the gray/white matter differentiation would not delineate the myelination itself, measurement of the signal intensity ratio of gray/white matter is a practical way to evaluate delayed myelination in a busy MR center. PMID- 8214346 TI - Biological rhythms in patients with lissencephaly (agyria-pachygyria). AB - Lissencephaly is a congenital malformation of the brain characterized by an extensive absence of cerebral gyral formation. Polysomnograms were recorded in 8 cases with lissencephaly (4 of agyria and 4 of pachygyria), and 24-h secretion of growth hormone, prolactin, luteinizing hormone, follicle-stimulating hormone and cortisol was examined in 6 of the 8 cases. The sleep-waking cycle and body temperature (BT) rhythm were studied in all 8 cases. The results were as follows: (i) the sleep-waking circadian rhythm was well preserved in 6 of the 8 cases; (ii) %REM (rapid eye movement) sleep decreased in 4 cases, but the ultradian rhythm of REM sleep was well observed in all cases except one; (iii) the secretion of GH and PRL showed normal or borderline increases with sleep; (iv) although these cases had not reached puberty, LH and FSH increased with sleep in 3 of 5 cases; (v) the circadian rhythm of cortisol secretion was preserved in all cases except one; (vi) BT showed a circadian rhythm after infancy. These findings suggest that the circadian rhythms function normally in lissencephaly, that the secretion of GH and PRL during sleep occurs almost normally, and that the cerebral cortex does not play a significant role in the regulation of these biological rhythms in lissencephaly. PMID- 8214347 TI - Brain perfusion SPECT in children with frequent fits. AB - We studied 14 children with frequent fits using 99mTc-HM-PAO single photon emission computed tomography (SPECT). There were 11 patients with partial secondary generalized epilepsy (PSGE) and 3 with Lennox-Gastaut syndrome (LGS). The typical regional cerebral blood flow (rCBF) finding in PSGE was a single area of abnormally low perfused cortex, and that in LGS, multiple hypoperfused areas. Clinically, the LGS patients were more severely affected. SPECT was more sensitive in detecting abnormalities than EEG, CT or MRI. Extensive impairment of rCBF may thus indicate unfavourable development of intellectual performance and poor seizure control. PMID- 8214348 TI - Lack of serum neutralizing antibody against poliovirus in patients with juvenile distal spinal muscular atrophy of upper extremities. AB - Serum neutralizing antibodies for type 1, 2 and 3 poliovirus were studied in 15 Chinese patients in Taiwan with juvenile distal spinal muscular atrophy of the upper extremities and 15 age-matched normal subjects. Significantly lower serum antibody titers were found in the study group, suggesting that patients with this chronic focal form of acquired motor neuron disease are, to some degree, immunologically unresponsive to the neutralizing epitope of poliovirus. PMID- 8214349 TI - A case of Duchenne muscular dystrophy with truncated dystrophin. Significance of a cysteine-rich domain for functional expression of dystrophin protein. AB - A Duchenne muscular dystrophy case showed truncated dystrophin (320 kDa) with an isoelectric point slightly shifted towards a more alkaline pH. From the polymerase chain reaction and immunochemical analysis data, the expressed dystrophin protein was predicted to lack the portion comprising the tail of the rod-like domain, the cysteine-rich domain, and the head of the C-terminal domain. These results indicated the functional importance of the cysteine-rich domain in the dystrophin protein. PMID- 8214350 TI - Electroencephalographic features of epileptic drop attacks and absence seizures: a case study. AB - A study of epileptic drop attacks (EDA) by simultaneous video-polygraphic recordings was carried out in one epileptic patient with myoclonic astatic seizures (Doose syndrome). EDA was shown to correspond to a burst of generalized bilaterally synchronous spike and wave complexes (GBSSW) at 3 Hz. Absence seizures were also observed with a burst of GBSSW with similar characteristics. The amplitudes of the corresponding slow wave component of GBSSW among the three intensities of atonia, i.e. complete atonia, minor atonia and no discernible atonia (control), was compared. A high amplitude was demonstrated to correspond with more pronounced atonia and a lower amplitude with reduced or absent atonia. These findings suggest that EDA corresponding to GBSSW have a neurophysiological mechanism in common with absence seizures, and that if the GBSSW is intense, it may be sufficient to cause immediate loss of global muscle tone. PMID- 8214351 TI - The use of intravenous immunoglobulin in Miller Fisher syndrome. AB - We report a patient with Miller Fisher syndrome who was treated with an intravenous high-dose of immunoglobulin. This syndrome is considered to be a benign variety of acute inflammatory demyelinating polyneuropathy (Guillain-Barre syndrome). However, there have been several reports of the need for ventilatory support and a few cases have had a fatal outcome. We observed a case of progressive Miller Fisher syndrome in a 3-year-old boy. Following 2 episodes of apnea lasting about 50 s each, he was treated with intravenous immunoglobulin (400 mg/kg/day) for 5 consecutive days. His respiratory state, general muscle strength, truncal ataxia and emotional state improved remarkably after this therapy. PMID- 8214352 TI - Familial schizencephaly. AB - Schizencephaly is a brain malformation characterized by infolding of cortical gray matter along a hemispheric cleft near the primary cerebral fissures. Although the etiology is unknown, genetic counseling has not been advocated because of its sporadic occurrence. We describe a family with two affected siblings. Both cases were characterized by hemiparesis, lack of gestational or postnatal complications, and diagnostic radiologic findings. We raise the possibility of a genetic etiology in some cases of schizencephaly and suggest a re-examination of the need for genetic counseling. PMID- 8214353 TI - Familial periventricular nodular heterotopia. AB - We describe herein a 13-year-old girl, her 34-year-old mother and her 60-year-old grandmother who have periventricular heterotopic nodules. The mother has suffered from epileptic seizures since she was 15 years old, but the daughter and grandmother have had no epilepsy. They showed multiple uncalcified nodules on the lateral ventricular walls on CT. On MRI the intensity of the nodules was the same as that of the cerebral gray matter, suggesting heterotopia, and no other cerebral abnormalities were observed. Despite extensive examinations, neither have exhibited evidence of tuberous sclerosis. The periventricular nodular heterotopia observed in this family are a unique form of migration disorders, which may be caused by a dominant mutation. PMID- 8214354 TI - Classification of the cerebro-oculo-muscular syndrome(s). Commentary to Kimura's paper (pp. 182-91) PMID- 8214355 TI - Fukuyama-type congenital muscular dystrophy and the Walker-Warburg syndrome. Commentary to Kimura's paper (pp. 182-91) PMID- 8214356 TI - Massive thymic enlargement associated with myasthenia gravis and hyperthyroidism. PMID- 8214357 TI - Tumor necrosis factor-alpha in malignant disease. AB - PURPOSE: Due to its important role in immunoregulation, we have investigated serum levels of tumor necrosis factor-alpha (TNF alpha), in children with newly diagnosed, untreated, malignant disease. PATIENTS AND METHODS: These levels have been related to the presence of infection and to the serum content of three other cytokines, namely interleukin-1 beta, interleukin-2, and interferon-gamma. All cytokine analyses were performed using highly sensitive radioimmunoassays. RESULTS: Children with leukemia had higher mean levels of TNF alpha (63.6 +/- 12.3 pg/ml) than did children with solid tumors (21.5 +/- 4.2 pg/ml) and control patients (10.5 +/- 2.6 pg/ml). TNF alpha levels in patients did not correlate with the levels of the other cytokines or with the presence of infection. CONCLUSIONS: Children with malignant disease often have elevated TNF alpha levels. This elevation is dependent on the malignant disease process itself, and could either reflect the host immunological response or tumor cell production of TNF alpha. PMID- 8214358 TI - Brief unconscious sedation for painful pediatric oncology procedures. Intravenous methohexital with appropriate monitoring is safe and effective. AB - PURPOSE: We report here our experience in using intravenous methohexital (MHX), an ultrashort-acting barbiturate, for brief unconscious sedation of pediatric oncology outpatients undergoing painful, invasive procedures. METHODS: Following published monitoring guidelines for deep pediatric sedation, 1.0 mg/kg MHX was administered immediately before the procedure, 1% xylocaine was given locally, and MHX was additionally titrated to maintain minimal response to pain during the procedure. Clinical data reported here were gathered retrospectively from permanent medical records. RESULTS: Data reported here represent 132 evaluable consecutive procedures in 33 patients ranging in age from 1.6 to 20.5 years. Patients underwent an average of 4 +/- 3 procedures and received a mean total MHX dose per procedure of 5.8 +/- 2.1 mg/kg. The mean length of time from start of sedation to full arousability was 30 +/- 12 min. Twenty-three (17.4%) procedures were associated with clinically insignificant decreases in diastolic blood pressure or heart rate below resting normal ranges for age. Eight (6.1%) procedures in six patients were associated with minor complications requiring no intervention, such as transient behavioral changes, transient myoclonus, and minimal stridor. Five procedures (3.8%) in five patients required simple suctioning to manage secretions. Only two procedures (1.5%) in two patients required brief bag-mask ventilation plus suctioning for suspected laryngospasm. None required intubation. No differences in clinical features or MHX doses were noted for patients with, as compared to those without, complications. All procedures were completed with a satisfactory level of sedation. CONCLUSIONS: Our experience indicates that MHX, with appropriate monitoring as described here, is a safe and effective agent for use in pediatric oncology outpatient sedation programs. PMID- 8214359 TI - Bone marrow transplantation for Fanconi anemia. Adjustment of the dose of cyclophosphamide for preconditioning. AB - PURPOSE: Five patients with Fanconi anemia have been treated by bone marrow transplantation. PATIENTS AND METHODS: They were conditioned with cyclophosphamide (CY) (20-150 mg/kg), antilymphocyte globulin, and thoracoabdominal irradiation (4-6 Gy). The dose of CY for preconditioning was adjusted individually, based on the in vitro effect of CY metabolites on the chromosomes of patients with Fanconi anemia. Four patients received marrow from human leukocyte antigen (HLA)-identical siblings, and one received marrow from his HLA phenotypically identical father. RESULTS: All patients achieved engraftment, and acute graft-versus-host disease (GVHD) grade II or more was not observed. Three developed chronic GVHD. All patients are surviving 2-5 years after grafting, with hematological improvement. CONCLUSIONS: These results indicate that the individual dose adjustment of CY used for preconditioning may prevent graft failure and severe acute GVHD. PMID- 8214360 TI - Transient erythroblastopenia of childhood. Evidence for cell-mediated suppression of erythropoiesis. AB - PURPOSE: T cell-mediated red cell aplasia in a 4 1/2-year-old child with transient erythroblastopenia of childhood (TEC) is described. PATIENTS AND METHODS: Erythropoiesis was studied by assessing the colony growth of marrow erythroid progenitors at the time of diagnosis and during recovery. RESULTS: The colony-forming unit-erythroid (CFU-E) growth of whole marrow at diagnosis was only 28% that of the control. T-cell depletion of the patient's marrow was followed by a more than fivefold increase in CFU-E growth, as compared with 20% inhibition of CFU-E and 40% inhibition of burst-forming unit-erythroid (BFU-E) growth in control marrow. The number of colony-forming unit-granulocyte macrophage (CFU-GM) in both control and patient's marrow was not significantly altered by all of these manipulations. During early and late recovery, CFU-E and BFU-E growth improved substantially, and the effect of T-cell depletion diminished. Increased numbers of peripheral T-suppressor lymphocytes, as well as activation of natural killer (NK) cells and high levels of interferon, all consistent with viral infection, were found at presentation. Clinical recovery was associated with normalization of T-suppressor lymphocyte number. CONCLUSIONS: The results suggest that in this child with TEC, a preceding viral infection may have caused activation of suppressor T-cells and interferon secretion leading to cell-mediated suppression of erythropoiesis. PMID- 8214361 TI - Transient abnormal myelopoiesis of infancy associated with trisomy 21. AB - PURPOSE: A unique myelodysplastic syndrome referred to as transient abnormal myelopoiesis (TAM) has been reported to occur primarily in infants with Down's syndrome (DS) or other abnormalities of chromosome 21. This disorder raises basic questions regarding the pathogenesis of leukemia, yet its natural history is poorly documented and derives from small series and isolated case reports. PATIENTS AND METHODS: To better characterize TAM, we accumulated data on 35 cases identified through a questionnaire mailed to pediatric oncologists in the United States. These cases, pooled with two that we recently encountered, and 58 comparable cases reported in the literature comprise a series of 95 cases of TAM in DS. RESULTS: The patients in this series were notable for the high morbidity and mortality of this reportedly benign condition. Eleven percent of the patients died during the initial event, and the overall mortality for the entire series was 27%. Twenty-eight of the 85 patients (33%) who survived the initial event developed a subsequent hematologic disorder, most often acute nonlymphocytic leukemia, at a median age of 16 months. CONCLUSIONS: No initial clinical or hematologic features predicted the development of a subsequent hematologic disorder. However, those patients initially mosaic for the presence of trisomy 21 did not develop subsequent abnormalities. This series reviews questions regarding leukemogenesis in DS and underscores the importance of conducting future prospective studies of this unique hematologic disorder. PMID- 8214362 TI - Thrombosis in children receiving L-asparaginase. Determining patients at risk. AB - PURPOSE: A prospective study of coagulation in 15 children who received L asparaginase, vincristine, or prednisone plus or minus an anthracycline as part of a treatment program for leukemia or leukemia-lymphoma syndrome was conducted. PATIENTS AND METHODS: One patient developed a central nervous system thrombosis. RESULTS: The inhibitors of coagulation, including antithrombin-III, protein C, protein S, and plasminogen, were decreased in many individuals, but were not significantly different in the patient who had experienced the thrombotic event. Platelet aggregations to low molar ADP were performed in four patients, and in three patients showed a hyperaggregable pattern. CONCLUSIONS: The patient with thrombosis developed a transient acquired type II pattern on multimeric analysis of the von Willebrand factor, which was not seen in the other individuals studied. PMID- 8214363 TI - Hypercalcemia: a dose-limiting toxicity associated with 13-cis-retinoic acid. AB - PURPOSE: 13-cis-Retinoic acid (cis-RA) has efficacy in the treatment and prevention of certain malignancies. In vitro effects against neuroblastoma include induction of differentiation, inhibition of proliferation, and decreased N-myc expression. We hypothesized that cis-RA may be effective against minimal residual disease in neuroblastoma patients. A phase I trial to determine the maximal tolerated dosage and toxicity of cis-RA in pediatric patients with neuroblastoma after bone marrow transplantation was initiated. PATIENTS AND METHODS: Forty-nine pediatric patients (status post-bone marrow transplant for neuroblastoma) were treated for 14 days with oral cis-RA in escalating doses from 100 to 200 mg/m2/day followed by a 14-day rest period for up to 12 months. RESULTS: In three of 39 patients (7.7%) evaluable for calcium levels, hypercalcemia (12.6-18.7 mg/dl) was the dose-limiting toxicity. Grade 1-3 hypercalcemia occurred in nine of 39 patients (23%). The overall incidence of hypercalcemia was 31% (12 of 39). Only one patient was symptomatic due to the hypercalcemia, with arthralgias and myalgias. The hypercalcemia resolved with temporary discontinuation of the drug and a 25% dose reduction for subsequent courses. CONCLUSIONS: Hypercalcemia is a novel dose-limiting toxicity for cis-RA. Patients receiving high doses of cis-RA should have monitoring of serum calcium levels. PMID- 8214364 TI - Acute myocardial infarction complicating prothrombin complex concentrate therapy in an 8-year-old boy with hemophilia A and factor VIII inhibitor. AB - PURPOSE: An 8-year-old boy with mild hemophilia A and inhibitors developed an acute myocardial infarction during treatment with prothrombin complex concentrates. CONCLUSIONS: This rare complication warrants restriction of dosage and length of treatment with these products to the recommended guidelines. It also appears that noninvasive cardiac monitoring of these patients is beneficial. PMID- 8214365 TI - B19 parvovirus-induced anemia in a normal child. Initial bone marrow erythroid hyperplasia and response to intravenous immunoglobulin. AB - PURPOSE: Human B19 parvovirus infection may cause severe erythroid hypoplasia in patients with an underlying hemolytic anemia. We report a case of severe parvovirus-induced anemia with initial marrow erythroid hyperplasia in a child with no underlying hematologic disorder. CONCLUSIONS: The patient's rapid hemoglobin recovery after treatment with i.v. immunoglobulin further supports this form of therapy for children with parvovirus-induced anemia. PMID- 8214366 TI - Clinical features of primary human herpesvirus-6 infection in an infant with acute lymphoblastic leukemia. AB - PURPOSE: The primary infection with human herpesvirus-6 developed concurrently with diagnosis of acute lymphoblastic leukemia and initiation of intensive chemotherapy for the disease in a 4-month-old girl. RESULTS: Prolonged viremia persisted for 7 days in the presence of neutralizing antibodies, and clinical features such as prolonged febrile and diarrheal period, no appearance of skin rash, and marked bulging fontanelle for 7 days in the absence of the virus DNA in spinal fluid may suggest an atypical clinical course of exanthem subitum and an unusual viral replication in immunocompromised condition. PMID- 8214367 TI - Acute lymphoid leukemia associated with Maffucci's syndrome. AB - PURPOSE: Maffucci's syndrome is a nonhereditary congenital disorder associated with multiple enchondromas, soft tissue hemangiomas, or lymphangiomas. It carries an associated high risk of the development of malignant neoplasms, particularly sarcomatous transformation of an enchondroma, as well as other malignant mesodermal and nonmesodermal neoplasms. Hematopoietic malignancies arising in Maffucci's syndrome are exceedingly rare. We report the case of a 14-year-old girl with Maffucci's syndrome who developed acute lymphoid leukemia. PATIENTS AND METHODS: The patient presented at 18 months of age with enchondromatosis. Maffucci's syndrome was established at 10 years of age after the appearance of multiple hemangiomas. RESULTS: At 14 years of age the patient developed fatigue, frequent nosebleeds, easy bruising, and weight loss, with circulating blasts in the peripheral blood. Bone marrow examination showed replacement of marrow spaces with leukemic blasts. Immunohistochemical and flow cytometric findings were consistent with a diagnosis of acute lymphoblastic leukemia with myeloid antigen expression. CONCLUSIONS: The occurrence of acute leukemia in a patient with Maffucci's syndrome may represent predisposition to yet another malignancy and reflect further expression of a generalized mesodermal dysplasia in these patients. It also emphasizes the need for aggressive surveillance in patients with Maffucci's syndrome. PMID- 8214369 TI - Alveolar soft part sarcoma. A rare tumor of unusual evolution in pediatrics. AB - PURPOSE: A case of alveolar soft part sarcoma of the arm with metastatic pulmonary miliaria is reported in a 12-year-old girl. RESULTS: Although the size of the metastases increased greatly and progressively for 9 years with no improvement under chemotherapy, the patient's general condition remained good. CONCLUSIONS: The course in pediatric oncology of this rare mesenchymatous tumor is very unusual; the histologic pattern is characteristic but the histogenesis remains unclear. The treatment of choice is tumoral excision. Other therapies involving secondary deposits are far from satisfactory, and the prognosis is poor because of the high rate of metastases. PMID- 8214368 TI - Yersinia enterocolitica bacteremia in a chronically transfused patient with sickle cell anemia. Case report and review of the literature. AB - PURPOSE: Yersinia enterocolitica sepsis is rarely encountered in patients without an underlying susceptibility and is most frequently reported in iron-overloaded patients. This is thought to be related to the unusual utilization of iron by this microorganism. We report a case of Y. enterocolitica bacteremia in a chronically transfused adolescent with sickle cell anemia. This type of serious infection in sickle cell disease is previously unreported. A description of the case and the relationship between Y. enterocolitica and iron is discussed. A review of the literature is presented. RESULTS: Y. enterocolitica can cause a severe septicemia, and increased virulence of this organism has been shown to correlate with increased iron burden and/or use of the chelator deferoxamine. It may also occur as a consequence of a contaminated blood transfusion. CONCLUSIONS: We believe our case demonstrates that Y. enterocolitica should be considered a possible pathogen in febrile chronically transfused patients with sickle cell disease. Broad antibiotic coverage should be initiated and deferoxamine discontinued pending results of cultures. PMID- 8214370 TI - Pulmonary carcinoma associated with hamartoma in an 11-year-old boy. AB - PURPOSE: We describe a poorly differentiated adenocarcinoma of the lung in an 11 year-old boy who had had a pulmonary hamartoma for at least 8 years. CONCLUSIONS: A hamartoma, even if clinically silent, may lead to the development of malignant tumors on rare occasions. PMID- 8214371 TI - Localized non-Hodgkin's lymphoma of the testis in a child. PMID- 8214372 TI - Frostbite: experience with rapid rewarming and ultrasonic therapy. Part II. 1960. PMID- 8214373 TI - Peripheral non-freezing cold injury: immersion injury. PMID- 8214375 TI - Treatment of frostbite. PMID- 8214374 TI - Psychological and psychophysiological factors in prevention and treatment of cold injuries. AB - Cold injured patients in Alaska come from many sources. Although sport and work continues to provide large numbers of cold injured, most severe repeat injuries tend to reflect other biopsychosocial consequences. Certain behaviors can increase the probability of injury, however all persons living in cold climates are potential candidates. One can decrease risk by education, knowledge and intelligent behavior. Proper respect for adequate protection and hydration seem to be critical factors. Understanding the psychological, physiological and psychophysiological aspects of the cold environment performer helps refine the prevention and treatment strategies for cold injury. Skill training with bio behavioral methods, such as thermal biofeedback, and the value of medical psychotherapy appear to offer continued promise by facilitating physiologic recovery from injury, as well as assisting in long term rehabilitation. Both approaches increase the likelihood of a favorable healing response by soliciting active patient participation. Medical Psychotherapy for traumatic injuries can also help identify and manage cognitive emotional issues for families and patients faced with the permanent consequences of severe thermal injuries. Thermal biofeedback therapy has the potential benefit of encouraging greater self reliance and responsibility for self-regulating overall health by integrating self-management skills regarding physiology, diet and lifestyle. Inpatient and outpatient biofeedback training offers specific influence over vascular responses for healing, as well as providing an effective tool for pain management. Interest in cold region habitation has continued to expand our study of human tolerance to harsh, extreme environments. Biological, psychological, sociological, and anthropological views on adaptation, habituation, acclimatization, and injury in cold environments acknowledges the role of development, learning and educated responses to cold environments. The study of health, performance, and injury prevention in extreme isolated cold environments has important strategic and scientific implications. What is learned from behavioral studies of cold survival provides an opportunity to increase our scientific knowledge and understanding. These cold research findings can assist in our future exploration of cold, underwater farming at great depths, and to far distance space travel to cold planets. The relatively new research frontier "Polar Psychology" has evolved to study how interactions with cold environments can have both positive and/or negative consequences. This research simulates the psychological factors likely to be encountered while exploring isolated cold regions of distant galaxies. The psychological and psychophysiological correlates of cold experience appear to be a function of four interactive issues: the environment, genetic predisposition, learning or experience, and finally perception or cognition. Individual cold tolerance seems to relate heavily on sensation, perception and behavior.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8214377 TI - Frostbite and hypothermia--current concepts. 1973. PMID- 8214376 TI - Frostbite: experience with rapid rewarming and ultrasonic therapy. Part III. 1961. PMID- 8214378 TI - Frostbite. A discussion of the problem and a review of the Alaskan experience. 1973. PMID- 8214379 TI - Summary of treatment of the cold injured patient. 1980. PMID- 8214380 TI - Accidental hypothermia: management approach. 1980. PMID- 8214381 TI - Summary of treatment of the cold injured patient: hypothermia. 1983. PMID- 8214382 TI - Frostbite: experience with rapid rewarming and ultrasonic therapy: Part I. 1960. PMID- 8214383 TI - Summary of treatment of the cold injured patient: frostbite. 1983. PMID- 8214384 TI - Comments on this issue of Alaska Medicine--from then (1960) until now (1993). AB - The drugs used in frostbite injury care are: Plasma volume expanders (low molecular weight dextran); vasodilating agents (tolazoline hydrochloride); hypotensive agents (guanethidine monosulfate, reserpine); hemorrheologic agents (oxpentifylline); calcium blocking agents (nifedipine); sympatholytic agents (phenoxybenzamine hydrochloride); anticoagulating agents (heparin); thrombolytic enzymes (streptokinase, tissue plasminogen activator--TPA); an industrial solvent (dimethyl sulfoxide--DMSO); anti-inflammatory agents such as nonsteroidal drugs, and acetylsalicylic acid, Ibuprofen. As yet, no clear treatment policy has been determined for preventing injury secondary to the formation of oxygen free radicals, damaging neutrophils or reperfusion injury. The role of oxygen free radical scavengers and factors causing reperfusion injury is unclear at this date. Since that first reported series of 51 patients in 1960-61, 1,282 patients have been seen. Of that number, 1,026 had a diagnosis of frostbite; 151 were diagnosed as hypothermia; and 105 diagnosed as immersion injury. PMID- 8214385 TI - Cold and freezing: a historical chronology of laboratory investigation and clinical experience. PMID- 8214386 TI - Histopathologic correlates of structures seen on dermoscopy (epiluminescence microscopy). AB - Dermoscopy (epiluminescence microscopy) is an in vivo technique that enables the clinician to visualize a variety of structures in pigmented cutaneous lesions that are not discernible by naked-eye examination. To identify the histologic correlates of these structures, a series of 71 pigmented neoplasms was documented photographically with and without dermoscopy. These lesions then underwent total excision and careful step-sectioning so that the resulting histologic slides could be correlated with the dermoscopic photographs. The histologic correlates of the pigment network, brown globules, black dots, blotches, hypopigmented areas, white areas, grey-blue areas, and whitish veil are identified. The structures seen under dermoscopy have specific histologic correlates. Understanding these histopathologic correlates will allow clinicians to better evaluate the dermoscopic features of pigmented lesions. PMID- 8214387 TI - Mantleoma. A benign neoplasm with mantle differentiation. AB - Four cases of neoplasms with mantle differentiation are presented. The mantle (sebaceous mantle) is a well-described but little known part of the sebaceous gland cycle. In the resting phase of that cycle, the mantle is seen as cords of undifferentiated cells that emanate from the infundibulum of a hair follicle and droop down aside the follicle in the form of a mantle or skirt. Cyclically, vacuolated sebocytes appear at the terminus of these cords, singly, then in groups, and finally as fully developed sebaceous lobules and glands. Presumably, sebaceous glands involute to become undifferentiated mantles. Clinically, neoplasms with mantle distribution occur on the face. Three of our cases were found fortuitously in sections of tissue removed because of basal-cell carcinoma. One was thought by the clinician to be a basal-cell carcinoma. Histopathologically, mantleomas vary in complexity. Presumably early neoplasms consist only of cords and columns of undifferentiated epithelial cells that radiate from an infundibulum. Later on, these cords interweave in a retiform pattern that contains sebocytes of varying degrees of vacuolization and sebaceous ductal structures. Mantleomas are benign because none in our series recurred after surgical removal and no atypical neoplastic cells were seen histopathologically. PMID- 8214388 TI - Benign cephalic histiocytosis: a distinct entity or a part of a wide spectrum of histiocytic proliferative disorders of children? A histopathological study. AB - When benign cephalic histiocytosis (BCH) was described for the first time in 1971, it was considered a nosologic entity due to its peculiar clinical presentation, but in the last few years its individuality has been questioned because of histopathological features overlapping with other non-X histiocytoses such as generalized eruptive histiocytosis (GEH). To solve this question, we examined with light microscopy using blinded technique 18 biopsy specimens obtained from 14 patients affected by BCH in comparison with 4 biopsies of GEH, 11 biopsies of papular xanthoma, and 25 biopsies of juvenile xanthogranuloma (JXG) of childhood. In the examined specimens, we identified three distinct patterns of proliferation of histiocytes we named "papillary dermal," "lichenoid," and "diffuse." With the exception of some peculiar histopathological features of BCH, observed only in the "papillary dermal pattern," a close histological relationship was observed among BCH, GEH, and JXG early nonxanthomatous stage. Our data suggest that BCH might be a localized form of GEH or an aborted phase of JXG. PMID- 8214389 TI - Ultrastructural findings in mucocutaneous infections of patients seropositive to HIV. AB - Tissue samples from 19 HIV-seropositive immunocompromised patients suffering from oral hairy leukoplakia, chronic vesicular or ulcerative herpes simplex, chronic nonmetameric herpes zoster, secondary syphilis, condylomata acuminata, molluscum contagiosum, or disseminated cutaneous mycobacteriosis were examined ultrastructurally in order to better define the fine structure of the causative organisms in parasitic conditions and to clarify the host-parasite relationships. Taking into account the few data in the literature regarding the same disorders in immunocompetent subjects, no striking differences in the morphology of the infectious agents or in the types of parasitism were found. Nevertheless, isolated herpesvirus and papillomavirus virions were found outside the infected cells, and this observation, if confirmed in a larger series of cases, could suggest a persistent infectivity of the lesions in immunocompromised patients. Moreover, electron microscopy proved to be useful for diagnostic purposes; in one case of disseminated cutaneous mycobacteriosis, repeated cultures failed to grow the organism. PMID- 8214391 TI - Solitary keratoacanthoma is a squamous-cell carcinoma: three examples with metastases. PMID- 8214390 TI - Histopathology of actinic prurigo. AB - Actinic prurigo (AP) is an idiopathic familial photodermatosis seen in American Indians. We report on 17 patients; 16 had dermatitis and one had actinic cheilitis. Ten patients had acute dermatitis and six had chronic dermatitis. The histologies of acute AP and polymorphous light eruption (PLE; limited concept) are eczematous and indistinguishable. Both show spongiosis, superficial (and sometimes deep) perivascular lymphocytic infiltrates, and papillary dermal edema. Both also show vacuolar degeneration of the basal layer. In contrast, the chronic lichenified AP lesions are associated with marked hyperkeratosis, acanthosis, elongation of the rete ridges, and tissue repair. The large lymphoid germinal centers in the lamina propria are the main features of the lip histology. Seven biopsies were positive in the basal membrane zone on direct immunofluorescent testing, four were negative, and one was inconclusive. IgM was present in six and C3 in two. These immunofluorescent results are probably not significant. Immunofluorescent testing of the lip was negative. Although it is not possible to distinguish acute AP from PLE histologically, it is possible to differentiate the two conditions when chronic AP changes are present. PMID- 8214392 TI - Horny perifollicular mucinosis. An atypical pityriasis rubra pilaris-like eruption associated with HIV infection. AB - We present a case of pityriasis rubra pilaris (PRP)-like eruption, in association with human immunodeficiency virus (HIV) infection, clinically characterized by follicular papules with some elongated spines and comedo-like lesions. The lesions were located on the back, flanks, and proximal extremities. Orthokeratotic follicular plugs and perifollicular mucinous degeneration were consistently observed on three biopsies. The most characteristic histological features of PRP were absent. To our knowledge, this is the first reported case of this kind. Such a case could suggest an atypical PRP modified by HIV infection. It is also possible that it represents a new entity associated with advanced HIV infection (horny perifollicular mucinosis). PMID- 8214393 TI - Primary soft tissue lymphoma associated with mesenteric lipodystrophy. AB - Skin involvement in non-Hodgkin lymphoma is usually specific and may precede systemic manifestations of the disease by months or even years. We report the case of a man with an inguinal plaque lesion of 1 year's evolution, diagnosed as polymorphous lymphoplasmocytoid lymphoma (immunocytoma). The evaluation of spread only revealed mesenteric lipodystrophy, whose association with lymphoid processes is more common than would be expected. PMID- 8214394 TI - Localised histiocytic lipofuscinosis. An unusual pigmented lesion. AB - We report a case in an 86-year-old woman, of a localised aggregate of lipofuscin laden histiocytes presenting as a pigmented lesion with local itching. Histologically, there was a diffuse dermal infiltrate of mononuclear cells, predominantly histiocytes containing golden-brown pigment shown to be lipofuscin. The typical ultrastructural appearance of this pigment was demonstrated on electron microscopy, and adjacent iron deposition was confirmed. The etiology of this rare lesion is unclear. Clinical distinction from pigmented cutaneous malignancies may be difficult. PMID- 8214395 TI - Cutaneous cryptococcosis--primary versus secondary disease. Report of two cases with review of literature. AB - The clinical, immunological, and pathological features of solitary cutaneous cryptococcosis in two apparently healthy Chinese adults are reported. In patient 1, regional cryptococcal lymphadenopathy also occurred. Both patients showed lymphopenia with a proportionate decrease in T-helper and T-suppressor cells. Both skin and lymph node biopsies showed granulomatous inflammation and the presence of cryptococcus. A chancriform syndrome developed in patient 1, indicating primary cutaneous cryptococcosis. Chancriform syndrome is rare in cryptococcal skin infection, probably due to immunosuppression in susceptible patients. In patient 2, the deep dermal and subcutaneous inflammatory involvement and anatomic location of the lesion on the upper medial thigh are supportive of secondary skin disease. Unless negated by a reliable history, the following features are indicative of secondary disease: inflammation centered in deep dermis or subcutaneous fat, lesion on covered parts of body, and multifocal skin lesions. Some cases remain unclassifiable. In practice the distinction between primary and secondary cutaneous cryptococcal disease is not essential because less toxic, effective antifungal drugs are now available. PMID- 8214396 TI - Malignant epithelioid schwannoma of the skin showing partial HMB-45 positivity. AB - A malignant epithelioid schwannoma occurred on the right second toe of a 30-year old Japanese man. It was a firm, flesh-colored, benign-appearing nodule and measured 13 x 9 mm in diameter and 6 mm in height. To our knowledge, this is the first case of malignant epithelioid schwannoma occurring on the toe. Histopathology was characterized by a circumscribed nodule in the dermis that predominantly consisted of atypical large epithelioid cells with some spindle cells whose proliferation was similar to that of the Verocay bodies seen in ordinary schwannoma. Fontana-Masson staining demonstrated no melanin pigment in the tumor at the light microscopic level. The eosinophilic cytoplasm contained abundant glycogen and was positive for S-100 protein and HMB-45, as usually seen in melanomas. Electron microscopy revealed that there was an abundance of long spacing collagen in the extracellular matrix, and the cells contained numerous dense-cored granules. But no definite melanosomes were observed in any stage. As far as we are aware, this is the first case of a malignant epithelioid schwannoma showing HMB-45 positivity. PMID- 8214397 TI - Capture of the leader of shining path. A dermatologic disease changes the course of history. PMID- 8214398 TI - A critical analysis of textbooks of dermatopathology in historical perspective. Part 8. PMID- 8214399 TI - Letters from afar. PMID- 8214400 TI - Dysplasia. PMID- 8214401 TI - Lymphatic valves of the rat pancreas. PMID- 8214402 TI - Origin of Triton tumor. PMID- 8214403 TI - Alcohol and immunology--progress and questions. PMID- 8214404 TI - Attention allocation: effects of alcohol and information salience on attentional processes in male social drinkers. AB - The purpose of this study was to examine the interactive effects of alcohol and salience of social cues (personality traits) on allocation of attention in the intoxicated male social drinker. It was expected that inebriated subjects would preferentially attend to high threat relative to low threat information contingent on the information's personal relevance. Seventy-six participants received either alcohol or a placebo, or were in a control condition, and were given the opportunity to attend to personally salient or nonsalient positive, negative, and neutral information. Intoxicated participants viewed negative traits longer than did nonintoxicated subjects and attended to these traits longer in the salient than in the nonsalient condition. Findings are compared to the attention allocation model, and their implications for alcohol-mediated cognitive processes are discussed. PMID- 8214405 TI - Personality characteristics of sisters and spouses of male alcoholics. AB - Sisters of alcoholics from high-density multigenerational families were assessed to determine personality characteristics. Spousal similarity was evaluated in proband/spouse pairs and in spouse pairs from the parental generation, allowing for comparisons of selection versus contagion as explanations for this similarity. Sisters were found to differ from control women with respect to Alienation and Social Closeness from the Multidimensional Personality Questionnaire, and Scale 6 (Paranoia) from the Minnesota Multiphasic Personality Inventory. Only spouses from the parental generation were similar on Alienation, suggesting that exposure over time (contagion) leads to greater similarity in parents from High-Risk families. Modest correlations in spouse pairs from both generations suggest that assortative mating for Social Closeness occurs among the parents of these individuals from High-Risk families, and further suggest that a diminished level of Social Closeness for sisters of alcoholics may be mediated in part by additive genetic variance. It is concluded that assortative mating for particular traits may contribute to increased risk for alcoholism. Also, failure to mate assortatively for other traits (e.g., Traditionalism, Harm Avoidance) may also contribute to increased rates in High-Risk families. PMID- 8214406 TI - Acute and chronic alcohol tolerance in humans: effects of dose and consecutive days of exposure. AB - Male social drinkers received doses of either 0.75 or 1.0 g/kg body weight of alcohol over 5 consecutive days. The beverage was divided into three equal drinks, and subjects performed an eye-hand coordination motor task after each drink. The breath alcohol concentration (BAC) was assessed at each performance measurement period. Performance was also assessed when the BAC level on the descending limb of the BAC curve was similar to each of the three BAC measurements on the ascending curve. Each group developed chronic tolerance (comparing the daily postalcohol performance with the daily prealcohol performance) by the 4th day of exposure. The development of a degree of acute tolerance (assessed by comparing the performance on the ascending and descending limbs of the BAC curve) was not observed consistently in the 1.0 g/kg dose group, but was seen in more than half of the subjects in the 0.75 g/kg dose group by the 4th and 5th day of exposure. PMID- 8214407 TI - Toward an alcohol treatment entry model: a comparison of problem drinkers in the general population and in treatment. AB - Building on a model used in the health services literature, this article examines differences among problem drinkers in treatment and in the general population to understand treatment utilization further. Discriminant function analysis showed significant differences between treated and untreated groups for men and women. For women, lifetime general treatment history, ethnicity, and employment were major contributors to the model; for men, the most important variables were social consequences, treatment history, and employment. For women, only the domain of individual predisposing variables provided a unique contribution to the model (p < 0.01). For men, the individual predisposing (p < 0.001), need (p < 0.001), and enabling (p < 0.01) domains did so. Findings indicate important differences in the factors that influence treatment entry for women and men. PMID- 8214408 TI - Intravenous flunitrazepam in the treatment of alcohol withdrawal delirium. AB - Alcohol withdrawal delirium (AWD) requires treatment with an adequate sedative, anticonvulsant, and antipsychotic agent next to general intensive care measures. Optimal medication should have a rapid onset of action and the possibility of parenteral application. A specific antagonist should be available. Flunitrazepam is a benzodiazepine that fulfills all these criteria. Twenty five patients suffering from AWD (mean age 45 years) took part in an open trial and underwent treatment with infusions of flunitrazepam (concentration: 8 mg/250 ml NaCl; speed, 250 ml/hr). Psychopathological, vegetative, and vital parameters were assessed every hour. All patients survived. They were treated with a mean total dose (SD) of 83.9 (45.4) mg of flunitrazepam (1.3 mg/kg body weight), which induced sedation 13.2 (5.3) min after the initiation of intravenous treatment. The mean duration of AWD (85.1 +/- 39.4 hr) corresponded to other studies, whereas the frequency of preexisting and concomitant diseases was higher (92%) in our patients. A patient who suffered from bronchitis and had a nasopharyngeal tamponade showed severe respiratory depression after having received 4 mg of flunitrazepam. This complication remitted immediately when 0.5 mg of flumazenil was given intravenously. No epileptic manifestation was observed during the treatment or after discontinuation of flunitrazepam. Vegetative and psychopathological symptoms (tremor, sweating, hallucinations, confusion, and restlessness) remitted rapidly. Our data suggest that intravenous flunitrazepam can be an efficacious and safe alternative to traditional treatment strategies of AWD. PMID- 8214409 TI - Influence of socially desirable responding in a study of stress and substance abuse. AB - Socially desirable responding is the reluctance to admit unpopular beliefs or behavior in order to avoid making a negative impression. It poses a problem for researchers who rely on self-report of heavy drinking and drug use. The Marlowe Crowne Social Desirability Scale (SDS), which measures socially desirable responding, was administered to 1933 respondents in a general population survey. The relationships between SDS and various self-report measures were examined. SDS was not correlated with gender or race, it increased with greater age and decreased with higher socioeconomic status. With age and socioeconomic status controlled, SDS had a moderate negative relationship with alcohol and drug use, and a strong negative relationship with variables reflecting the expression of anger. Correlations between drinking/drug use and such variables as age, marital conflict, and stressful life events were not substantially changed by controlling for SDS. It was concluded that social desirability response bias probably results in underestimates of rates of heavy drinking and drug use, but does not compromise the study of predictors of heavy drinking or drug use. PMID- 8214410 TI - Alcohol, injury, and risk-taking behavior: data from a national sample. AB - The association of alcohol consumption and injury is well documented in the literature. It has also been suggested that alcohol consumption is associated with risk-taking behaviors. No studies have reported the association of alcohol consumption and risk-taking behaviors with injury across all injury types, however. Data were collected (1990) from a national probability household sample (n = 2058; weighted n = 1150) on: injuries that required treatment during the last year; quantity and frequency (Q-F) of drinking; and behaviors associated with risk perception, risk-taking/impulsivity, and sensation seeking. The injured (12% of the sample) were more likely to be male, younger, and to report moderate and heavy drinking and more frequent drunkenness compared with those with no injuries. They were also less likely to score high on risk perception and more likely to score high on risk-taking/impulsivity and sensation seeking than those with no injuries. However, using logistic regression analysis to predict a treated injury during the last year, only the interaction term of gender by Q-F was significant, with Q-F a significant predictor of injury among males but not among females. PMID- 8214411 TI - Subtypes of early age onset alcoholism. AB - Forty-three adolescents qualifying for a DSM-III-R diagnosis of alcohol abuse/dependence were classified according to the internalizing-externalizing behavior dimension. Two clusters were identified. The majority of subjects clustered into a group characterized by behavioral dyscontrol and hypophoria (history of suicide attempts) (cluster 2), whereas the other group was primarily featured by negative affect (cluster 1). Cluster 2 subjects demonstrated more severe alcohol and drug use-related problems, behavioral disturbances, and general psychopathology; lower prevalence of depressive disorders; and less severe anxiety disorders. These results, implicating two variants of adolescent alcohol abuse/dependence, suggest the need to tailor differential treatments to adolescents with alcohol abuse/dependence based on personality characteristics and clinical presentation. PMID- 8214412 TI - Simple reaction time event-related potentials: effects of alcohol and sleep deprivation. AB - The effects of two levels of alcohol intoxication and 30 hr of sleep deprivation on visual event-related potential (ERP) waveforms concomitant to simple reaction time (RT) were examined in 54 normal male subjects. In a previous study, we reported that alcohol and sleep deprivation each increased RT. At a 0.05 breath alcohol concentration (BAC), the combined treatments produced an additive increase in RT, whereas at a 0.08 BAC the combined treatments produced no increase beyond that seen with each alone. In this study we present the ERP findings. Sleep deprivation alone increased the latency of a 150 msec negative component (N1) of the ERP. Alcohol increased the latency of a 250 msec negative component (N2), but only in the absence of sleep deprivation. Furthermore, this increased latency of N2 was correlated with RT measures. These results suggested that sleep deprivation slowed initial stimulus detection, whereas alcohol slowed later processing and response activation. PMID- 8214413 TI - Sexuality of alcoholic women with menstrual cycle function: effects of duration of alcohol abstinence. AB - Although improvement in sexual function has been reported to occur in postmenopausal alcoholic women after long-term sobriety, little is known about the role alcohol abstinence may play in terms of improving sexual functioning in alcoholic women with menstrual cycle function. The responses of 58 menstruating alcoholic Italian women to a standardized questionnaire that included questions related to sexual function, behavior, and performance are reported. Women were categorized as alcohol abstinent (AA) for > 1 year (long AA, n = 22) or < 1 year (short AA, n = 36). In both groups, 100% reported that they had a regular sexual partner, and the response rate to the sexuality questions was > 99%. Compared with short AA women, long AA women were significantly older at the time of study, at menarche, and at onset of heavy drinking, alcohol dependence, and alcohol abstinence. Sexual desire was defined as willingness to engage in sexual activity; sexual capacity was defined as the ability to become sexually aroused; sexual responsiveness was defined as the ability to achieve orgasm. On all three measures, ts well as intercourse frequency, both long AA and short AA women improved significantly with alcohol abstinence. These findings suggest that sobriety, even of relatively short duration, improves sexual function in menstruating alcoholic women. PMID- 8214414 TI - Atypical liver alcohol dehydrogenase in the Spanish population: its relation with the development of alcoholic liver disease. AB - The presence of atypical liver alcohol dehydrogenase (ADH) was determined in samples of liver tissue from 222 alcoholic and nonalcoholic subjects to determine its prevalence in the Spanish population, and to evaluate the possible relationship between the presence of this isoenzyme and the development of alcoholism and alcoholic liver disease. Alcoholic patients were classified into the following groups: control subjects, with normal liver pathology (group 1), patients with noncirrhotic liver disease (group 2), and patients with cirrhosis of the liver (group 3). Nonalcoholic subjects were also divided, following the same criteria, into groups 4, 5, and 6, respectively. The prevalence of atypical ADH in the population analyzed was 16.2%. Atypical ADH was present in 14.9% of alcoholics and in 17.4% of nonalcoholics (p = NS). There were no significant differences when the prevalence of atypical ADH of alcoholic and nonalcoholic patients with similar degrees of liver pathology was compared (group 1 vs. 4, group 2 vs. 5, and group 3 vs. 6). The prevalence of atypical ADH was also similar in cirrhotic patients with respect to those of noncirrhotic liver disease and control patients, either in alcoholic or nonalcoholic groups. Our findings indicate that the prevalence of atypical ADH in the Spanish population is similar to that reported for other Caucasian groups. Moreover, the presence of atypical ADH does not play a role in the development of alcoholism nor in the development of alcoholic liver disease in the population analyzed. PMID- 8214415 TI - Alcohol and estrogen levels in postmenopausal women: the spectrum of effect. AB - Compared with alcohol-abstaining normal postmenopausal women, estradiol levels are known to be statistically increased in normal postmenopausal women who consume alcoholic beverages moderately, and to be even further increased in alcoholic postmenopausal women with cirrhosis. This study was undertaken to evaluate whether or not there is a spectrum of changes in levels of sex steroids and pituitary hormones associated with alcohol abstinence, alcohol use, and alcohol-induced cirrhosis in the absence of current alcohol abuse. For levels of estradiol and testosterone, as well as for the estradiol to testosterone ratio, all three groups differed significantly from each other; for the pituitary hormones, levels in the abstainers and alcohol users were similar and statistically different from levels in the alcoholic cirrhotic women. Compared with the alcohol-abstaining women, the relationships of age and estradiol with levels of the other hormones were disturbed for 4 of 11 correlations examined among the alcohol users, and for 9 of 11 correlations evaluated among the alcoholic cirrhotic women. These findings suggest that not only are hormonal relationships markedly disrupted among alcoholic cirrhotics, but also that alcoholic beverage consumption in the range of 0.1-28 total weekly drinks results in detectable perturbations of the normal hormonal relationships expected in postmenopausal women. PMID- 8214416 TI - Low-dose thyrotropin-releasing hormone effects in cognitively impaired alcoholics. AB - The cognitive effects of a low dose of thyrotropin-releasing hormone (TRH) (2.0 mg, IV) were evaluated in 18 chronic alcoholic patients who exhibited memory dysfunction secondary to chronic alcohol abuse. The study used a double-blind crossover design that compared cognitive functions in patients with 2.0 mg of TRH IV as compared with a placebo. TRH was chosen because of its ability to enhance cholinergic transmission. Only minimal effects were seen with TRH. Patients with a shorter duration of alcohol use (mean of 16 years) performed significantly better with TRH as compared with placebo on a test involving verbal learning and memory. Those with a more chronic history of alcohol abuse (mean of 27 years) did not show such a response. All of the subjects showed cardiovascular response to TRH. Factors that may have contributed to the results of our study are discussed. It is our impression that future studies evaluating the cognitive effects of TRH in chronic alcoholics need to include an evaluation of the functional activity of TRH in the brain. PMID- 8214417 TI - Decline in alcohol use among 7-12th grade students in New York State, 1983-1990. AB - The prevalence and patterns of alcohol use and alcohol-related problems were determined in two large representative samples of 7-12th grade students in New York State in 1983 and 1990. Comparable sampling procedures and measures were used in both surveys. Logistic regression analyses showed that overall drinking, heavy drinking, and alcohol-related problems decreased significantly for the population as a whole; furthermore, all subgroups according to age, gender, and racial/ethnic status showed significant declines in alcohol use and related problems over this time period. The social context of this change is discussed. PMID- 8214418 TI - Heart rate as an index of stress response in alcohol administration research: a critical review. AB - Heart rate has been a widely used measure in experimental investigations of alcohol and stress. Meaningful interpretations from this measure, however, may be threatened due to methodological problems. This article critically reviews alcohol administration studies that have utilized heart rate as an index of stress response. Potential confounds stemming from the use of heart rate are identified and suggestions for its future use are presented. Implications for high-risk studies are discussed. It is concluded that (a) the amount of time provided for the absorption of an alcohol or placebo beverage is highly correlated with postdrink heart rate change, (b) the magnitude of this postdrink heart rate change is highly associated with the probability of finding a subsequent stress response dampening effect, and (c) offspring of alcoholics appear to manifest a heightened heart rate response to alcohol, which may account for apparent enhanced stress response dampening effects among these subjects. PMID- 8214419 TI - Effects of ethanol on cultured fetal astroglia. AB - This study investigated the effects of a 4-day ethanol exposure on cultured rhombencephalic astroglia. The contents of astroglial protein and DNA, and astroglial uptake of serotonin (5-HT) were determined. Fetal rhombencephalic astroglia were examined because of this laboratory's evidence that in utero ethanol exposure markedly impairs the development of serotonergic neurons, which are located in this fetal brain area, and because of the recently demonstrated importance of local support glia in neuronal development. The results of these experiments demonstrated that protein was significantly reduced in astroglia cultured in ethanol at either 150 or 300 mg/dl. In addition, these astroglia exhibited decreased [3H]5-HT uptake per well. However, no significant ethanol associated differences were detected when [3H]5-HT uptake was expressed per mg protein rather than per well. In contrast to the effects of a 4-day ethanol exposure, the acute ethanol exposure did not significantly alter astroglial uptake of [3H]5-HT/well. In addition, the 4-day exposure to 50 to 300 mg/dl of ethanol did not significantly alter astroglial DNA content. In summary, it appears that a 4-day exposure of cultured fetal rhombencephalic astroglia to 150 to 300 mg/dl of ethanol reduces astroglial protein content and astroglial 5-HT uptake. A reduction in total astroglial proteins, potentially including those that act as essential growth factors, could contribute to some of the ethanol associated alterations in central nervous system development. PMID- 8214420 TI - Ethanol alters hormone production in cultured human placental trophoblasts. AB - Maternal alcohol abuse during pregnancy can lead to abnormalities in fetal development, including the fetal alcohol syndrome (FAS). Although intrauterine growth retardation is a hallmark of FAS, the pathophysiology is not fully understood. A contributing factor may be altered placental function, which could affect fetal growth and development. As a major endocrine organ during pregnancy, changes in the production of placental hormones could affect pregnancy and possibly fetal development. In this study, the effect of continued exposure to ethanol on placental hormone production was examined using cultured human placental trophoblasts. Ethanol exposure involved diffusion of ethanol from the atmosphere into the culture medium. This was refreshed daily, leading to daily peak concentrations of 280 to 300 mg/dl (60-65 mM) at 16 to 24 hr. This ethanol exposure for 2 or 4 days significantly increased the production of human chorionic gonadotropin and progesterone by the cultured trophoblasts. However, ethanol treatment had no effect on human placental lactogen production. Acute stimulation (10 min) of cultured trophoblasts with adenosine (50 microM) normally results in increased production of cyclic adenosine 3',5'-monophosphate (cAMP). With ethanol exposure, adenosine-stimulated cAMP production was significantly elevated relative to that in controls. However, the effect of ethanol on adenosine-stimulated cAMP did not appear to be secondary to chronic alterations in adenosine in the culture medium. Measurement of adenosine in the culture medium revealed no difference in concentration or production between control and ethanol treated groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214421 TI - Immune function in offspring of nonhuman primates (Macaca nemestrina) exposed weekly to 1.8 g/kg ethanol during pregnancy: preliminary observations. AB - A preliminary investigation of immune host response was conducted in a group of fetal alcohol-exposed nonhuman primates (Macaca nemestrina) who were part of a broader ongoing study of ethanol teratogenicity. The mothers of the offspring received weekly oral doses of ethanol (1.8 g/kg) for the first 3 or 6 or the entire 24 weeks of gestation. A control group received sucrose solution weekly throughout pregnancy. Four of the 18 ethanol-exposed animals (22%) died or were euthanized after infectious disease or failure to thrive during the first year of life; none of the seven control animals died. This imbalance in survival prompted the present review of immune function in the remaining offspring. Parameters assessed included: (1) white blood cell count (WBC), (2) peripheral blood leucocyte subsets (CD4+, CD8+, CD20+, and CD11c+), (3) T-cell proliferation after activation with phytohemagglutinin (PHA), staphylococcus enterotoxin B (SEB), and tetanus toxoid (TT), (4) phagocytic activity of monocytes, and (5) serum immunoglobulin levels and serum antibody titers after TT vaccination. Mean T-cell proliferation to TT was significantly decreased (p = 0.01) in all ethanol-exposed animals relative to controls, with near-significant decreases (p = 0.06) in response to SEB in the ethanol-exposed animals. Lymphocyte proliferation in response to PHA was not altered. Ethanol-exposed animals had significantly lower TT titers than controls after initial vaccination and booster. WBC, leukocyte subsets, serum immunoglobulins, and monocyte phagocytic activity were not significantly different from control values. These preliminary observations suggest that T-cell proliferation and antigen-specific memory responses may be altered in offspring exposed to weekly doses of ethanol in utero and warrant further evaluation for confirmation. PMID- 8214422 TI - Cloning and expression of the full-length cDNAS encoding human liver class 1 and class 2 aldehyde dehydrogenase. AB - The amino acid sequences of both human class 1 and 2 aldehyde dehydrogenase (ALDH) and the sequences of the genes coding for them are known. Based on this sequence data, we designed primers and isolated the full-length cDNAs encoding both isozymes from a human liver mRNA pool. cDNAs were subcloned in the plasmid pT7-7 and expressed in Escherichia coli with a yield of approximately 3 mg ALDH protein/liter of cell culture, although only one-third of the enzyme was soluble. The soluble recombinantly expressed ALDHs were purified to homogeneity using a hydroxyacetophenone-Sepharose affinity column. The mitochondrial isozyme had a subunit molecular weight of 55 kDa, an isoelectric point of 4.9, and a specific activity of 1.10 units/mg, which were in good agreement with that from the native enzyme. The expressed cytosolic isozyme had the same subunit molecular weight (55 kDa) and pI (5.4) as that reported for the native enzyme and had a specific activity of 0.26 units/mg. The expressed mitochondrial isozyme could be recognized by antibodies raised against rat mitochondrial ALDH, whereas the cytosolic isozyme could be recognized by antibody raised against horse cytosolic ALDH. PMID- 8214423 TI - Sex differences and the effects of alcohol on immune response in male and female rats. AB - Although it is clear that both alcohol and sex hormones impact immune function, very little information is available on the effects of alcohol on immune response in males versus females. We decided to determine if the alterations in immune response resulting from alcohol feeding might be expressed differently in males and females. To accomplish this we utilized pair-fed male and female Sprague Dawley rats. Animals were fed a liquid diet for 60 days containing 30% of their calories as ethanol, and after 1 week this concentration was increased to 45% ethanol. Controls received liquid control diet of the same caloric and nutritional composition, and immune status was monitored with in vivo and in vitro techniques. Ethanol feeding significantly reduced the phytohemagglutinin skin response in males (p = 0.020) and females (p = 0.012). The concanavalin A blastogenic response of spleen cells prepared from female rats fed ethanol was significantly depressed with respect to spleen cells prepared from female rats fed the control diet (p = 0.0071). Alcohol also appeared to depress spleen cell blastogenic response in males, but this trend did not quite reach significance (p = 0.071). Spleen cells from groups of ethanol and control male and female rats were labeled with fluorescent monoclonal antibodies and run on a Fluorescent Activated Cell Sorter. Ethanol significantly increased the percentage population of CD4 (T-helper cell) in males (p = 0.017), but not in females, and promoted an apparent, although nonsignificant, increase in the CD4/CD8 ratio in both sexes. An ELISA was used to measure IgM and IgG antibody elaborated by pokeweed mitogen stimulated spleen cells in cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214424 TI - Chronic ethanol ingestion modifies the renin-aldosterone axis independent of alterations in the regulation of atrial natriuretic peptide. AB - Using an animal model, we have investigated the effects of chronic ethanol ingestion on the regulation of atrial natriuretic peptide (ANP) synthesis and release. Male Sprague-Dawley rats were maintained for 6 weeks on a liquid diet of ethanol (up to 20% v/v) as part of a 2% solution of calf milk replacer. Weight matched controls received an equal volume of ethanol-free solution, and normal animals drank ad libitum. All animals received rat chow throughout the experiment. This model produced physiologically relevant levels of blood ethanol, as concentrations at the time of sacrifice were 171.98 +/- 39.26 mg/dl. Plasma renin activity was significantly elevated in response to ethanol treatment, whereas circulating aldosterone concentration was reduced. No alterations in the plasma or atrial tissue levels of ANP were evident, although we did observe a significant increase in the ventricular tissue levels of ANP from 45.1 to 71.8 ng/g as a consequence of ethanol treatment. Levels of both atrial and ventricular ANP mRNA were not different between alcohol-treated and liquid-restricted control animals, although both groups showed significant increases in the amount of transcript in comparison with rats drinking ad libitum. No significant increases in either arterial blood pressure or heart/body weight ratio were observed for ethanol-treated rats. These results suggest that modifications in the renin aldosterone axis can occur independently of alterations in the regulation of ANP under the influence of chronic ethanol ingestion. PMID- 8214425 TI - Impact of chronic alcoholism on the aging rat: changes in nutrition, liver composition, and mortality. AB - The adverse effects of chronic alcohol consumption (mean 6.68 g/kg/d) were assessed in 150 male Sprague-Dawley rats over their life span (25 months). Evaluations were performed at 2, 3, 8, 13, 19, and 25 months of age for changes in nutrition status, biochemical tests for liver injury, compositional changes in liver, and hepatic regenerative capacity. In spite of nearly identical caloric intake, alcohol treatment was associated with nutritional levels 10-30% lower than controls. Maximal changes were observed at the two extremes of ages (2-3 months and 19-25 months). Hence, a nutritional contribution to other adverse changes could not be excluded. Fatty compositional increases (triglycerides) occurred early (5-fold increases after 1 month of treatment) then declined to levels only slightly above controls. Biochemical tests on sera for liver injury (AST and total bilirubin) were consistently higher with alcohol treatment. Regenerative capacity measured by [3H]thymidine uptake after partial hepatectomy was initially elevated in the alcoholic then rapidly declined beyond 7 months of age. In control animals, an age-related decline was also observed but occurred later beyond 12 months of age. Consistent with these adverse effects, ethanol diet survival was poorer than the pair-fed control groups by 15% (median survival for alcoholics, 17 months vs. 20 months in controls. PMID- 8214426 TI - Female rats release more corticosterone than males in response to alcohol: influence of circulating sex steroids and possible consequences for blood alcohol levels. AB - The hypothalamic-pituitary-adrenal (HPA) axis of female rats is more responsive to a variety of stimuli than that of males. Proestrous females are also reported to release more ACTH and corticosterone in response to restraint stress than females at other stages of the estrous cycle. Finally, blood alcohol levels (BALs) reached in response to a standard dose of alcohol also indicate the presence of a gender specificity, with females exhibiting higher BALs than males. The aim of this study was therefore 2-fold: first, we investigated the influence of gender on the ability of alcohol to increase plasma ACTH and corticosterone secretion in the rat. Second, we tested the hypothesis that corticosterone alters alcohol metabolism and asked whether this might represent a mechanism underlying the sex difference in BALs. We observed that compared with intact males, intact females taken at random stages of the estrous cycle secreted significantly (p < 0.01) more ACTH and corticosterone in response to alcohol (0.2-1.8 g/kg). Within females, the intraperitoneal administration of alcohol was followed by higher plasma ACTH and corticosteroids levels during proestrus and estrus, compared with diestrus. Removal of circulating sex steroids abolished the gender difference in terms of ACTH secretion, but ovariectomized females still released more corticosterone than castrated males in response to 0.6 and 1.8 g alcohol/kg. This difference could not be explained by a sex-related component of pituitary responsiveness to corticotropin-releasing factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214427 TI - Increased natural killer cell activity in a model of immunoglobulin A nephropathy secondary to chronic alcohol consumption. AB - We investigated natural killer (NK) cell activity in an animal model of ethanol induced immunoglobulin A (IgA) nephropathy. Two groups, of 10 rats each, received a continuous intragastric infusion of liquid diet through a permanent cannula for 6 weeks. The alcoholic group was infused additionally with intragastric ethanol, representing from 32% to 40% of the caloric requirement. The group of control rats received an isocaloric diet supplemented with glucose instead of alcohol. IgA nephropathy was observed in all the alcoholic rats but in none of the controls. NK cell activity was investigated in the two groups by measuring the cytotoxicity of spleen cells using the chromium release method. NK cell activity was found to be significantly increased in the alcoholic rats. In view of the known modulation of IgA synthesis by NK cells, we suggest that increased NK cell activity may be a contributing factor to the high levels of circulating IgA seen in IgA nephropathy secondary to chronic alcohol consumption. PMID- 8214428 TI - Age-related differences in sensitivity to alcohol in the rat. AB - Female F344 rats of three different ages (4, 13, and 25 months) were tested for sensitivity to the ataxic, hypothermic, and hypnotic effects of injected ethanol. Challenges with ethanol sufficient to produce similar blood alcohol concentrations (BACs) in all age groups at the time of testing were observed to produce greater ataxia in old rats (25 months > 13 months > 4 months). Old rats also were observed to recover the righting reflex at lower BACs than those present in young or middle age rats. BAC at a target rectal temperature of 36 degrees C was observed to be lower in old than in young or middle-age rats when measured as body temperature was falling after doses of 3.0 g/kg to old and 3.5 g/kg to young and middle rats. However, no differences among groups in BAC at target temperature (36 degrees C) were observed as body temperature was recovering from peak hypothermia back up to 36 degrees C. With the exception of the last observation cited, these findings appear to confirm and extend earlier reports of increased target tissue sensitivity to ethanol with advancing age in rodents. PMID- 8214429 TI - Effects of postnatal exposure to alcohol on reproductive physiology and sexually dimorphic behavior in a marsupial, the gray short-tailed opossum (Monodelphis domestica). AB - The effects of postnatal exposure to alcohol on reproductive physiology and sexually dimorphic behavior and anatomy in adult male and female gray short tailed opossums were examined. Female responsiveness to male pheromones and fertility in both sexes were essentially normal in postnatally alcohol-treated animals. However, aspects of sexually dimorphic behavior were masculinized and defeminized in females and demasculinized in males following gonadectomy in adulthood and treatment with male (testosterone) or female (estradiol) hormones. The possible role of alterations in neural aromatase activity by perinatal alcohol exposure in mediating these behavioral effects and the potential use of this marsupial species in perinatal alcohol studies are discussed. PMID- 8214430 TI - Production of antibodies that recognize the heterogeneity of immunoreactive sites in human hemoglobin chemically modified by acetaldehyde. AB - Human hemoglobin (Hgb) was incubated with acetaldehyde under two different conditions: (a) in the presence of 250 mM acetaldehyde for 1 hr then reduced with 100 mM NaCNBH3 for an additional 4 hr at room temperature; and (b) in the presence of 500 mM acetaldehyde for 10 days at room temperature and then reduced with 1 mM NaBH4 for 1 hr. It was found that 44% and 27% of free amino groups in Hgb-acetaldehyde adduct (AA) remained unmodified when Hgb was treated under conditions (a) and (b), respectively. SDS-PAGE analysis revealed that the molecular weight of Hgb-AA(a) [Hgb modified under condition (a)] was slightly greater than that of unmodified Hgb and extensive protein cross-linking had occurred in Hgb-AA(b) [Hgb modified under condition (b)]. Electrophoresis on agarose gel showed the order of negative charge was Hgb-AA(b) > Hgb-AA(a) > unmodified Hgb. Polyclonal antibody raised in rabbits using keyhole limpet hemocyanin as the carrier protein modified by acetaldehyde under condition (a) [i.e., KLH-AA(a)] preferentially recognized Hgb-AA(a), whereas antibody raised using KLH-AA(b) as the immunogen recognized only Hgb-AA(b). In conclusion, antibodies raised with protein-AA antigens produced under different conditions recognize different epitopes. PMID- 8214431 TI - Dose- and age-dependent effects of prenatal ethanol exposure on hippocampal metabotropic-glutamate receptor-stimulated phosphoinositide hydrolysis. AB - Prenatal ethanol exposure reduces the density of the N-methyl-D-aspartate (NMDA) receptor agonist binding sites and decreases the capacity to elicit long-term potentiation (LTP) in hippocampal formation of 45-day-old rat offspring. We hypothesized that prenatal ethanol exposure would reduce metabotropic-glutamate receptor (mGluR)-activated phosphoinositide hydrolysis also. Sprague-Dawley rat dams were fed a liquid diet containing either 3.35% (v/v) ethanol or 5.0% ethanol throughout gestation. Control groups were pair-fed either isocalorically matched 0% ethanol liquid diets or lab chow ad libitum. (1S,3R)-1-aminocyclopentane-1,3 dicarboxylic acid (trans-ACPD) stimulated inositol-1-phosphate (IP1) accumulation via activation of the mGluR in offspring whose mothers consumed the 3.35% ethanol liquid diet was not different compared with the control groups. Furthermore, trans-ACPD stimulated IP1 accumulation in 10- to 13-day-old offspring of the 5.0% ethanol diet group was not different compared with the control groups. However, trans-ACPD stimulated IP1 accumulation was reduced significantly in 56- to 82-day old offspring of dams fed the 5.0% ethanol liquid diet compared with the control groups. In contrast, bethanechol stimulated IP1 accumulation, mediated via activation of muscarinic cholinergic receptors, was not affected by maternal consumption of either ethanol liquid diet. These results suggest both dose- and age-dependent effects of prenatal ethanol exposure on hippocampal responsiveness to trans-ACPD-activated phosphoinositide hydrolysis. Furthermore, the ability of the 3.35% ethanol diet to alter hippocampal NMDA receptors without altering the mGluR response suggests a differential sensitivity to the effects of ethanol exposure in utero among hippocampal glutamate receptor subtypes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214432 TI - Comparison of levels of cytochromes P-450, CYP1A2, CYP2E1, and their related monooxygenase activities in human surgical liver samples. AB - Hepatic microsomal cytochromes P-450 CYP1A2, and CYP2E1 contents and catalytic activities have been simultaneously investigated in 42 patients undergoing diagnostic liver biopsy. CYP1A2 contents, measured by Western blotting, were correlated with methoxyresorufin-O-demethylation and ethoxyresorufin-O deethylation (r = 0.65 and r = 0.66, p < 0.001, respectively). CYP2E1 contents were correlated with 1-butanol oxidation and 6-hydroxylation of chlorzoxazone (r = 0.75 for both, p < 0.001). CYP1A2 catalytic activities varied by 30- to 40 fold, whereas CYP2E1 activities varied by 6- to 20-fold. In our study, these variations were not related to liver diseases or cancer of the digestive tract nor to alcohol drinking or smoking habits, because patients were alcohol- and tobacco-free for 1 month before the study. Other environmental factors, diet habits, and/or genetic factors could explain the large interindividual variations observed. PMID- 8214433 TI - Fetal alcohol exposure attenuates lipopolysaccharide-induced fever in rats. AB - Exposure to alcohol in utero can lead to long-lasting impairments of immune functions and to decreased resistance to infectious agents. We studied the effects of fetal alcohol exposure (FAE) in rats on the core body temperature response to an exogenous challenge of the immune system with lipopolysaccharide (LPS). We report that FAE rats show markedly decreased LPS-induced fever [i.e., they require a higher dose than control rats to show any LPS-induced hyperthermia (50 micrograms/kg vs. 10 micrograms/kg)], and even with the higher LPS dose they manifest a weaker hyperthermia, which declines faster than in control animals. These results suggest that FAE produces an impairment in the release of endogenous pyrogens and/or in the neural substrate for body temperature regulation. This impairment may account for at least some of the decreased resistance to infections observed in FAE animals and humans. PMID- 8214434 TI - Purification and partial amino acid sequence of a high-activity human stomach alcohol dehydrogenase. AB - To understand the relative importance of alcohol dehydrogenase (ADH) isoenzymes in gastric ethanol metabolism, a stomach-specific ADH (sigma-ADH) was purified to homogeneity from human transplant donor and surgical tissues, and its activity for ethanol oxidation was examined. The enzyme from these tissues had a specific activity at pH 10 of approximately 70 units/mg, about 10 times that reported by Moreno and Pares (J. Biol. Chem. 266:1128-1133, 1991). The enzyme exhibited a high Km for ethanol at pH 7.5 and 10 (29 and 5.2 mM, respectively). This high activity sigma-ADH isoenzyme migrated on starch and isoelectric focusing gels to a position slightly anodic to the liver pi pi isoenzyme. It was subjected to digestion by endoproteinases, and approximately 40% of the protein was sequenced. The sigma-ADH exhibited 75%, 68%, and 62% sequence identity to the human class I (beta 1), II (pi), and III (chi) isoenzymes, respectively, and 61% identity to the deduced ADH6 amino acid sequence. Phylogenetic analysis indicated that precursors to this high-activity sigma-ADH and the class I isoenzymes diverged more recently than precursors to the class II and III isoenzymes, after reptilian and avian divergence. The high-activity sigma-ADH isoenzyme therefore represents a distinct class of ADH (class IV), more closely related in evolution to the class I isoenzymes than to the other known human isoenzymes. PMID- 8214435 TI - Ethanol metabolism in deermice: role of extrahepatic alcohol dehydrogenase. AB - The relative contributions to ethanol metabolism of extrahepatic alcohol dehydrogenase (ADH) and of liver microsomes were assessed in deermice, which lack hepatic low Km ADH (ADH-). In vitro kinetic studies showed the existence of high Km (> 1 M) ADH activity in the liver and kidney, and an enzyme with intermediate Km in the gastric mucosa (Km = 133 mM), whereas the low Km ADH was missing. With deuterated ethanol, ADH- deermice showed a significant exchange of reducing equivalents that had been equated with ethanol metabolism by others, whereas we found a poor correlation between the rate of exchange and the rate of metabolism. In vitro studies with subcellular fractions, isolated hepatocytes, and tissue slices revealed that neither liver, nor kidney, nor stomach from ADH- deermice contributed to exchange of reducing equivalents. These findings clearly indicated that the ADHs with high or intermediate Km of the tissues studied are not responsible for the exchange. Furthermore, gastrectomized ADH- deermice still showed an exchange of reducing equivalents, thereby dissociating exchange from gastric ADH activity. Moreover, pretreatment with cimetidine (50 mg/kg body weight), an inhibitor of gastric ADH, did not alter the rate of total ethanol elimination when ethanol was given intraperitoneally. In conclusion, when ethanol was given parenterally, the microsomal ethanol-oxidizing system rather than gastric ADH is a major pathway of ethanol oxidation in ADH- deermice, whereas both pathways contribute significantly to the metabolism of orally administered ethanol. PMID- 8214436 TI - Lp(a) levels increase after ethanol withdrawal. PMID- 8214437 TI - Alcohol, deafness, epilepsy, and autism. PMID- 8214438 TI - Vitamin E and ethanol-enhanced carcinogenesis. PMID- 8214439 TI - Early dermatologic signs of alcohol abuse. PMID- 8214440 TI - [Undifferentiated carcinoma of nasopharyngeal type sitting in the hypopharynx]. AB - Nasopharyngeal-like carcinoma is an extremely rare tumor when localised in the laryngopharyngeal mucosa. Only 10 of such tumors could be found by the AA. in the medical literature. They report this additional case in which the radiotherapy plus the chemotherapy have controlled, till now, the primary disease and its spreading to the cervical lymph nodes. PMID- 8214441 TI - [Histopathological aspects of the benign lymphoreticulosis, cat scratch disease, or cervical localization]. AB - Report about 2 children affected with the cat scratch disease or lymphoreticulosis. The AA. discuss some etiological and clinic features of the malady, especially emphasizing the typical anatomopathological findings, which in the majority of the occurrences, allow the actual diagnosis. This is a disease of low incidence, but must be bear in mind when dealing with any cervical lump. PMID- 8214442 TI - [Tuberculosis of the parotid gland]. AB - We present a case of parotid tuberculosis diagnosed through F.N.A.C. (fine needle aspiration cytology). Due to this rare extrapulmonary location of the tuberculosis, the AA. make a review of the last 12 years concerning literature together with a monographic study of the process. PMID- 8214443 TI - [Cervical cystic metastasis in ENT carcinoma. Differential diagnosis with the branchioma]. AB - This study report 3 cases of nodal cystic metastasis in the neck. One of them was diagnosed as an epidermoid carcinoma of unknown origin and the other 2 were an epidermoid carcinoma and an mucoepidermoid carcinoma respectively, arising in the larynx. Treatment of these patients included removal of the cystic metastasis with or without neck dissection and irradiation. Cystic metastasis from squamous cell carcinoma have often been mistaken for primary squamous cell carcinoma of branchiogenic origin. The distinctive histological features of cystic metastasis reviewed after its correct identification, can lead to the discovery of an unsuspected primary lesion and result in specific treatment options. PMID- 8214444 TI - [The Stewart-Morel syndrome in the differential diagnosis of patients with frontal headache]. AB - Hyperostosis frontalis interna is the name generally applied to skull thickening more or less restricted to the squamous portion of the frontal bone and involving, in particular, its subdural or inner surface. The association of this calvarial thickening with virilism and obesity is a clinic-anatomic complex often know as the Morgagni's syndrome and is also referred to as the Stewart-Morel syndrome or metabolic craniopathy, when accompanied by mental disorders. Hyperostosis frontalis interna is being discussed here mainly in connection with the Stewart-Morel's syndrome of which it is the pivotal feature. Frontal headache is a common complaint and is severe in some cases. In addition various neuropsychiatric disturbances may be manifested. PMID- 8214445 TI - [Reconstructive results in 31 cases using a myocutaneous flap from pectoralis major]. AB - A study was carried out about the general features of myocutaneous flap taken from the pectoralis major muscle. This flap is employed in the reconstructive step after ablative surgery for carcinomata of the oropharynx, tongue, floor of the mouth, hypopharynx and other growths of the neck with skin involvement. The AA. review their 31 cases results, both cosmetic and functionally, and consider that the end-condition is favorable and hopeful in the whole. PMID- 8214446 TI - [Deafness in patients with osteogenesis imperfecta]. AB - This study deals with 8 cases of progressive deafness in patients with abnormalities in growth and skeletal disease, suffering from Osteogenesis imperfecta (5 of them are a familial case). The work is both and audiological and radiological research of the temporal bone, done in order to uncover the reasons of the patient's deafness. This curses just like otosclerosis with a conductive component (fixation of the stapes) and a sensitive one (cochlear demineralization), starting up in adolescence as bilateral and symmetric process. Because of its progressive nature the AA, recommend as treatment the ear prostheses and refuse the surgery of the stapes. PMID- 8214447 TI - [Topical treatment of otorrhea]. AB - A study has been carried out with 167 cases of discharging ears treated topically by means of lavages with a formic solution followed by the instillation of a quantity of boric drops. The material and methods used are exposed, together with the results achieved, taking into account that most the cases had been previously multi-treated with antibiotherapy, with adverse outcome. This procedure is cheap, effective and with scarce side-effects. PMID- 8214448 TI - [The usefulness of provoked acoustic otoemissions in the study of olivo-cochlear reflex]. AB - The paper reports the experimental task done by the AA, in order to probe objectively the being of a feed-back circuit of cochlear interconnexion. This loop is basically represented by the medial efferent olivo-cochlear system. With that purpose they have analyzed the variations produced in the provoked acoustic otoemissions by clicks registered in one ear when the contralateral ear is stimulated with a white noise of 80 dB HL. The results shows that after stimulation of the contralateral cochlea with a white noise a decrease of the global amplitude of the PAOE is observed and also a decrease of the several amplitudes composing the frequency spectrum, but retaining the same morphological pattern. PMID- 8214449 TI - [Lymphoepithelioma of the larynx]. AB - Non-nasopharyngeal Lymphoepithelioma is a tumor of undifferentiated non keratinizing cells enclosed in an lymphocytic stroma. The lymphoid tissue does not participate in the tumor process. Its tendency is to precociously spreading in the lymph nodes and viscera, but shows a good radiotherapeutic response. Unlike the nasopharyngeal lymphoepithelioma there is no etiological relationship with the Epstein-Barr virus, in spite of the histological similitudes, therefore the pathogenesis must be different in each. Discrimination between lymphoepithelioma and other neoplasms of the epithelial lineage is important in order to indicate the treatment and also to provide prognostic information. PMID- 8214450 TI - Setting standards for cardiopulmonary resuscitation. PMID- 8214451 TI - Implicit memory during balanced anaesthesia. Lack of evidence. AB - The effect of the number of presentations on implicit memory for words was studied in anaesthetised patients. During standardised, balanced anaesthesia, 81 surgical patients were presented with less common specimens of familiar word categories. For each of three word categories the number of word presentations varied between the patients (0 (control), 5, or 30 presentations). Postoperatively, repetition priming was tested by asking patients to generate exemplars for each of the word categories. No implicit memory for the words presented during anaesthesia was found and consequently no effect of number of word presentations could be demonstrated. It is suggested that this finding, which contradicts previous results, may be caused by the relatively low familiarity of the words used. PMID- 8214452 TI - Propofol-fentanyl anaesthesia in cardiac surgery: a comparison in patients with good and impaired ventricular function. AB - The haemodynamic effects of propofol-fentanyl anaesthesia for elective cardiac surgery were compared in 24 patients with good left ventricular function (ejection fraction > 45%, left ventricular end-diastolic pressure < 16 mmHg) and nine patients with impaired function. Anaesthesia was induced with fentanyl 25 micrograms.kg-1 and pancuronium 0.1 mg.kg-1 and was maintained with a variable rate propofol infusion, mean rate 2.61 mg.kg-1 x h-1 in the good ventricular function group and 2.71 mg.kg-1 x h-1 in the impaired function group. Additional fentanyl 7.5 micrograms.kg-1 was given before sternotomy. Ventilation to normocarbia was with air and oxygen (FIO2 0.6). Haemodynamic measurements were made before induction, after tracheal intubation, before and after sternotomy and before aortic cannulation. There were no significant differences between the groups in any haemodynamic variables during the study. Twenty minutes after intubation both groups showed a decrease from pre-induction values in mean arterial pressure (p < 0.05) and left ventricular stroke work index (p < 0.05), the reduction in left ventricular stroke work index remaining significant during the prebypass period in both groups. There were no significant changes in right or left sided filling pressures, systemic vascular resistance or heart rate. The technique decreased cardiac work and effectively controlled the autonomic responses to sternotomy in both groups. This study suggests that propofol may be a suitable adjunct to opioid anaesthesia in patients with impaired ventricular function having cardiac surgery. PMID- 8214453 TI - Capnothorax: implications for the anaesthetist. AB - Ten patients underwent a laparoscopic surgical technique for thoracic and cervical dissection of the oesophagus during oesophagogastrectomy. Thoracotomy was avoided with potential benefits to the patient. To facilitate surgical access the right lung was collapsed using a double-lumen bronchial tube and carbon dioxide was insufflated into the right pleural cavity to compress the lung. Changes in haemodynamic and respiratory variables occurred. In the majority of the patients airway pressure and end-tidal CO2 increased, despite alterations in ventilation. In five patients systolic blood pressure decreased suddenly by between 15 and 35 mmHg, and in four patients SpO2 decreased to 91% or less, despite an FIO2 of 1.0. If carbon dioxide was insufflated too fast, or the lung failed to deflate adequately, the clinical picture was that of a tension pneumothorax. One patient developed surgical emphysema and a contralateral pneumothorax. Postoperatively two patients had recurrent laryngeal nerve damage. Suggestions are made to minimise the changes in haemodynamic and respiratory variables during carbon dioxide insufflation into the thorax. PMID- 8214454 TI - Laryngeal mask airway insertion. A comparison of the standard versus neutral position in normal patients with a view to its use in cervical spine instability. AB - The ease of insertion of the laryngeal mask airway with the patient's head in the standard position and the neutral position was compared, in a study of 80 healthy patients. Successful insertion was assessed by fibreoptic bronchoscopy and the functioning of the airway. In terms of function the successful insertion rate for the standard position was 100% (40/40) and for the neutral position 95% (38/40). There were no significant differences in scores as assessed by fibreoptic bronchoscopy. The laryngeal mask airway may have a role in the management of some patients with cervical spine instability, although confirmation of this ultimately depends on the results of outcome studies. PMID- 8214455 TI - Fibreoptic intubation. Influence of tracheal tube tip design. AB - A randomised study was carried out in 60 patients to assess the influence of tracheal tube tip design on the ease of railroading a tracheal tube during fibreoptic intubation. A new design of tracheal tube with a tapered tip, without a bevel, was compared with a tracheal tube of standard design. The new design was found to be greatly superior in both oro- and nasotracheal fibreoptic intubation, when compared with the traditional tracheal tube (p < 0.001). The shape of the tip of a tracheal tube is an important determinant of the ease of railroading the tube over an inserted fibrescope. PMID- 8214456 TI - Lumbar plexus block: an anatomical study. AB - The anatomy of the lumbar plexus and the various approaches used to perform lumbar plexus blockade are reviewed. A single needle technique for a posterior approach to the plexus at the L2-3 interspace is described. This technique was used bilaterally in six intact cadavers, and the extent of spread of an injected dye was documented photographically during a subsequent detailed dissection of the region. In all cases, dye was confined to the posterior part of the psoas muscle, and tracked down the nerves of the lumbar plexus. No dye was seen anterior to the psoas, around the sympathetic chain, on the sacral plexus or in the extradural or subarachnoid spaces. Further studies in patients with needle position and drug disposition being confirmed using computerised tomography and X ray scanning were in agreement with the results observed in the cadavers. This technique represents a simple approach to the lumbar plexus which does not require needle localisation by X ray screening. PMID- 8214457 TI - Near fatal pulmonary hypertension after surgical repair of congenital diaphragmatic hernia. Successful use of inhaled nitric oxide. AB - The addition of 10-20 parts per million nitric oxide to the inspired gas was successful in controlling near fatal pulmonary hypertension after surgical repair of a congenital diaphragmatic hernia in a neonate. A preceding prostacyclin infusion was unable to prevent the failure of pulmonary perfusion. No side effect of nitric oxide therapy was observed, and ventilatory support could be substantially reduced as a result of the treatment. On the basis of the striking and lifesaving effects of nitric oxide therapy demonstrated in this child, we believe that nitric oxide treatment will prove to be a major contribution to the management of postoperative pulmonary hypertensive crises. PMID- 8214458 TI - Cardiorespiratory arrest following combined spinal epidural anaesthesia for caesarean section. AB - A 31-year-old woman had an elective Caesarean section under combined spinal/epidural anaesthesia. At the end of the operation, diamorphine 2.5 mg in 5 ml of 0.25% bupivacaine plain was injected through the epidural catheter. Forty minutes after this, the patient had a cardiorespiratory arrest in an ordinary postnatal ward. PMID- 8214459 TI - Inadvertent suppression of a fixed rate ventricular pacemaker using a peripheral nerve stimulator. AB - Electromagnetic interference usually produces only minor effects in patients with pacemakers. Nevertheless, the possibilities of serious and even fatal consequences of this complication must be recognised. This case reports an unusual anaesthetic source of interference, caused by activation of a popular nerve stimulator, resulting in cardiac arrest in a patient with a fixed-rate ventricular pacemaker. PMID- 8214460 TI - A computer-controlled closed anaesthetic breathing system. AB - We describe the design and working of a computer-controlled, closed anaesthetic breathing system which rapidly achieves and maintains a prescribed end-tidal concentration of isoflurane in oxygen. The system is simple to set up and not expensive; the only nonstandard component is a modified glass syringe. We have demonstrated that gas analysers may contribute as much as the patient to the accumulation of nitrogen within the breathing system. Details of our clinical experience with the system are presented in an accompanying article. PMID- 8214461 TI - Near infrared spectroscopy in adults. Does the Invos 3100 really measure intracerebral oxygenation? AB - Does the Invos near infrared spectroscopy monitor detect intracranial oxygenation, or reflect oxygenation of extracerebral tissues? The change in Invos regional cerebral oxygenation was studied during a doubling of middle cerebral artery flow with hypercapnia. There was no significant change in regional cerebral oxygenation, which suggests that the Invos does not reflect intracerebral oxygenation, possibly because of its narrow optode separation. The use of near infrared spectroscopy in adults may require a more powerful machine. PMID- 8214462 TI - Evaluation of pulse oximetry during cardiopulmonary resuscitation. AB - This study evaluates whether the pulse oximeter is useful during cardiopulmonary resuscitation. The instrument was of undoubted benefit in the management of primary respiratory arrest, but of equivocable value in cardiac arrest. Data were displayed during external chest compressions, but were generally unreliable. The ear probe was not able to produce a consistently good signal during cardiopulmonary resuscitation. Nevertheless, the provision of an oximeter amongst the first-line resuscitation equipment available at a cardiopulmonary arrest significantly altered the management of seven out of 20 patients, five of whom survived. PMID- 8214463 TI - Beyond the lung: oxygen delivery and tissue oxygenation. PMID- 8214464 TI - John Mervyn Nooth. An update and some Bath memorials. PMID- 8214465 TI - Zingiber officinale (ginger)--an antiemetic for day case surgery. AB - The effect of powdered ginger root was compared with metoclopramide and placebo. In a prospective, randomised, double-blind trial the incidence of postoperative nausea and vomiting was measured in 120 women presenting for elective laparoscopic gynaecological surgery on a day stay basis. The incidence of nausea and vomiting was similar in patients given metoclopramide and ginger (27% and 21%) and less than in those who received placebo (41%). The requirement for postoperative antiemetics was lower in those patients receiving ginger. The requirements for postoperative analgesia, recovery time and time until discharge were the same in all groups. There was no difference in the incidence of possible side effects such as sedation, abnormal movement, itch and visual disturbance between the three groups. Zingiber officinale is an effective and promising prophylactic antiemetic, which may be especially useful for day case surgery. PMID- 8214466 TI - An audit of extradural infusion analgesia in children using bupivacaine and diamorphine. AB - One hundred and fifty extradural infusions of diamorphine and bupivacaine after major surgery in children were audited over a 15 month period. The majority of the children (69%) were less than 5 years of age. Analgesia was assessed or self rated as 'very good' in over 75% of patients. Urinary retention was seen in 11% of patients and pruritus in 10%. Respiratory depression requiring intervention was only seen in one patient--a premature infant of 39 weeks post-conceptual age. Technical complications resulted in the early loss of 16.7% of the infusions. Although analgesia was good the complexity of the extradural infusion technique demanded significant medical and nursing time especially to overcome technical problems. PMID- 8214467 TI - A combined chest drain and intrapleural catheter for post-thoracotomy pain relief. AB - This study examined the effectiveness of a new type of chest drain, which incorporates an additional lumen within its wall to facilitate the administration of intrapleural bupivacaine. Nine patients who received a bolus dose of 1.5 mg.kg 1 bupivacaine with 1:200,000 adrenaline through this chest drain used less morphine, and had lower visual analogue pain scores in the first 6 h after thoracotomy than patients in whom a standard chest drain had been used. Bupivacaine levels were found to be within safe limits in all patients. PMID- 8214468 TI - The anaesthetist and HIV. PMID- 8214469 TI - Pathogenesis of postimmersion collapse. PMID- 8214470 TI - Detection of leaks in anaesthetic machines. PMID- 8214471 TI - Leakage of fresh gas from vacant CO2 cylinder yoke. PMID- 8214472 TI - Oxygen delivery and oxygen consumption. PMID- 8214473 TI - Insertion technique for reinforced laryngeal mask airway and its use in recovery. PMID- 8214474 TI - Regurgitation using a laryngeal mask. PMID- 8214475 TI - The laryngeal mask airway: safe in the X ray department? PMID- 8214476 TI - Percutaneous dilational tracheostomy. PMID- 8214477 TI - Percutaneous dilational tracheostomy. PMID- 8214478 TI - Percutaneous dilational tracheostomy. PMID- 8214479 TI - Critical incident 10 years later--ability to cope and other behavioural factors. PMID- 8214480 TI - Disconnection and inspired oxygen alarms--a hazard. PMID- 8214481 TI - Abreaction and midazolam. PMID- 8214482 TI - Pulmonary artery catheters--a new complication. PMID- 8214483 TI - Intra-operative heat loss--wrapping up the problem with a space blanket. PMID- 8214484 TI - ENT and eye anaesthesia: to spray or not to spray--a rationalisation. PMID- 8214485 TI - Unusual defect in a Tuohy needle. PMID- 8214486 TI - A safe anaesthetic in Huntington's disease? PMID- 8214487 TI - Sinus arrest during cholecystectomy. PMID- 8214488 TI - Getting back to normal. PMID- 8214489 TI - The uptake of isoflurane during anaesthesia. AB - The uptake of isoflurane at a constant end-expired concentration of 1.5% in oxygen was studied in 15 women, ASA 1 or 2, undergoing elective total abdominal hysterectomy. The anaesthetic was administered by a simple computer-controlled to and-fro closed system. After an initial period of wash-in to the system, the rate of uptake of isoflurane decreased bi-exponentially with a rapid reduction during the first 15 min. Perturbations from this bi-exponential decline reflect changes in cardiac output. The mean (SD) cumulative use of isoflurane was 4.5 (0.43) ml after 30 min and 7.3 (0.79) ml after 60 min. PMID- 8214490 TI - Intranasal fentanyl titration for postoperative pain management in an unselected population. AB - A randomized, double-blind study was undertaken to investigate the suitability of intranasally administered fentanyl for postoperative pain management under routine conditions in an unselected population. For postoperative pain relief, patients received either 0.027 mg fentanyl intranasally and sodium chloride 0.9% intravenously (intranasal group, n = 53) or sodium chloride 0.9% intranasally and 0.027 mg fentanyl intravenously (intravenous group, n = 59). These doses were repeated every 5 min until the patients were free of pain or refused further analgesia. Pain severity was evaluated before beginning opioid titration and 5, 10, 15, 20, 30, 40, 50, 60, 70 and 80 min thereafter. Adequate pain relief was achieved in 52 of 53 patients in the intranasal and in all patients in the intravenous group. Pain intensities evaluated on a 101-point numerical rating scale as well as on a verbal rating scale decreased significantly in both study groups within 5 min. At the 15 min measurement point, numerical rating scale pain intensity and at the 10 and 20 min point, verbal rating scale pain intensity was significantly lower in the intravenous group. The incidence of side effects was low in both groups and no patient complained of intranasal pain. Intranasally administered fentanyl would appear to be suitable for the management of postoperative pain. PMID- 8214491 TI - The influence of the H1 and H2 receptor antagonists, terfenadine and ranitidine on the hypotensive and gastric pH effects of the histamine releasing drugs, morphine and tubocurarine. AB - Morphine and tubocurarine may release histamine by direct mast cell degranulation which may result in systemic effects such as cutaneous flushing, local wheal and flare formation and hypotension. This randomised, double-blind study examined whether preoperative combined oral terfenadine (60 mg) and ranitidine (150 mg) attenuates the reduction in blood pressure and cutaneous flushing after the administration of tubocurarine and morphine in 60 patients undergoing elective gynaecological surgery. In addition, investigation was made of whether tubocurarine and morphine cause a significant decrease in gastric pH in comparison to the nonhistamine-releasing agents fentanyl and vecuronium. Patients were randomly assigned to one of three groups receiving either pre-operative terfenadine and ranitidine and intra-operative tubocurarine and morphine (group A); pre-operative placebo and intra-operative tubocurarine and morphine (group B); pre-operative placebo and intra-operative fentanyl and vecuronium (group C). Compared to group B, group A had less hypotension and tachycardia but no significant decrease in cutaneous flushing immediately following morphine and tubocurarine (p > 0.05). There were no significant differences in haemodynamic changes between the groups A and C. In those patients not pretreated with terfenadine and ranitidine (groups B and C), gastric pH decreased between 5 and 10 min following bolus administration of morphine and tubocurarine (group B), whereas patients receiving fentanyl and vecuronium (group C) had an increase in gastric pH. This suggests that histamine release following administration of morphine and tubocurarine is sufficient to increase gastric acidity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214492 TI - Creatinine and 51Cr-EDTA clearance after liver transplantation. AB - We have compared glomerular filtration rate measured by creatinine clearance with that measured by 51Cr-EDTA clearance after liver transplantation. Fourteen pairs of values were obtained from seven patients on the first and second days after operation. There were wide discrepancies between the values for glomerular filtration rate measured by the two methods, with a regression co-efficient of 0.43 (p = 0.12). Both methods assume a steady state, with no change of extracellular fluid volume or in the rates of exchange between physiological compartments, that does not apply in the immediate period after operation. The results show the difficulties of using clearance techniques to assess renal function after major surgery. Since drug therapy may be based on these measurements, we suggest that in this group of patients isolated clearance values should not be used. PMID- 8214493 TI - Implicit learning during enflurane anaesthesia in spontaneously breathing patients? AB - Forty-one patients breathing spontaneously during enflurane anesthesia were presented (via headphones) either with statements about common facts of some years ago, or new verbal associations, i.e. names of fictitious people. Postoperatively, there were no differences between the two groups in the responses to questions about the common facts or attribution of fame to the fictitious people. This finding suggests that unconscious learning and activation may not occur during enflurane anaesthesia without neuromuscular block. PMID- 8214494 TI - Intra-arterial versus intravenous regional analgesia for hand surgery. AB - Twenty-six adult patients participated in this study of intra-arterial and intravenous regional analgesia. The radial or the brachial artery was cannulated in patients randomised to receive intra-arterial regional analgesia and a hand vein was cannulated in patients randomised to receive intravenous regional analgesia, with a 22-G cannula. A double cuffed tourniquet and Esmarch's bandage were used. Lignocaine 0.5%, (1.5 mg.kg-1 intra-arterially, and 3.0 mg.kg-1 intravenously) was injected over 3 min. There were two failures (one in each group). Intra-arterial injection of lignocaine was more painful than intravenous injection. Onset and offset of analgesia, surgical and tourniquet pain scores, motor blockade, and bruising after cannulations were similar. Surgical conditions were good in all patients having intra-arterial regional analgesia, fair and poor in five having intravenous regional analgesia (ns). Three of the intravenous regional analgesia patients had transient adverse affects after tourniquet release (ns). No permanent sequelae of cannulations were observed. It is concluded that intra-arterial regional analgesia with lignocaine 0.5%, 1.5 mg.kg 1 has similar onset, offset, quality, failure rate and patient acceptance, as intravenous regional analgesia with lignocaine 0.5%, 3.0 mg.kg-1. PMID- 8214495 TI - A preliminary assessment of epidural chloroprocaine for day procedures. AB - Twenty-five patients underwent epidural anaesthesia with a new formulation of chloroprocaine 3% (1.0-1.5 ml x 10 cm body height-1) for a variety of day procedures. The mean (range) duration of surgery was 17 (5-35) min. The mean (range) time taken to establish maximal block was 16 (15-21) min and the mean (range) time to ambulation was 78 (55-95) min after administration of chloroprocaine. Twenty-three patients experienced a decrease in systolic arterial blood pressure of up to 15% of baseline values with another two decreasing by up to 25%. Two patients complained of severe backache immediately after operation and a further 16 and four patients reported mild or moderate backache respectively. Operating conditions were excellent in all but one patient and 23 patients said they would be happy to have the same anaesthetic again. PMID- 8214496 TI - Classification and severity of postdural puncture headache. Comparison of 26 gauge and 27-gauge Quincke needle for spinal anaesthesia in day-care surgery in patients under 45 years. AB - Two hundred and five patients, aged 16-45 years, undergoing day care surgery were given a spinal anaesthetic using either a 26- or a 27-gauge Quincke point spinal needle. The occurrence of headache and accompanying symptoms postoperatively was analysed from 186 returned questionnaires. The incidence of classical postdural puncture headache was 4.5% following the use of a 26-gauge needle and 8% with a 27-gauge needle (p > 0.05). A further group of patients suffering headache after dural puncture was identified, the postdural puncture-related headache. The headache and accompanying symptoms were similar to that seen with a postdural puncture headache except that it was not aggravated by posture. A system of grading the severity of both type of headache is presented and standardised criteria for the classification of postdural puncture headache are proposed. PMID- 8214497 TI - Repeated doses of suxamethonium in the myasthenic patient. AB - The neuromuscular block of successive doses of suxamethonium 100 mg, monitored by electromyography, was investigated in a myasthenic patient (class IIB), undergoing thymectomy. The results suggest that successive doses of suxamethonium in the myasthenic patient are followed by a progressive prolongation of the neuromuscular block. This may be attributed to rapid desensitisation of the myasthenic endplate receptors and the rapid development of phase II block, as evidence by a progressive decrease of the T4/T1 ratio. PMID- 8214498 TI - A blind nasal intubation using a laryngeal mask airway. PMID- 8214499 TI - Postpartum meningitis. PMID- 8214500 TI - Three diagnostic conundrums solved using the laryngeal mask airway. PMID- 8214501 TI - Pharyngeal teratoma. AB - A 30-week newborn patient presented with acute respiratory obstruction due to a large pharyngeal teratoma. At laryngoscopy no view of the larynx was obtained, and a tracheal tube was unintentionally passed blindly into the oesophagus. This relieved the obstruction by anterior displacement of the mass. PMID- 8214502 TI - A comparison of keyed and non-keyed vaporizer filling modes and volatile agent wastage. AB - Two hundred and forty bottles of enflurane were collected after their contents had been emptied into vaporizers equipped with keyed or non-keyed filling ports. The volume of agent remaining, the residual volume, was measured. There was a greater (p < 0.001) residual volume in 'empty' bottles which had been used to fill keyed compared with non-keyed enflurane vaporizers. Five hundred and fifty two bottles of isoflurane were also collected after they had been used to fill keyed vaporizers. There was no significant difference between the residual volume remaining in bottles of isoflurane and enflurane used to fill keyed fillers; however, the difference was statistically significant if the residual volume was expressed as a proportion to the volume of agent contained in the full bottle. The results show that volatile anaesthetic agent wastage is increased by the use of keyed fillers. Isoflurane wastage caused by utilisation of keyed fillers could be reduced by a factor of 2.5 by supplying isoflurane in 250 ml rather than 100 ml bottles. PMID- 8214503 TI - Noninvasive blood pressure measurements with single and twin-hose systems--do mixtures matter? AB - Noninvasive blood pressure monitors which use twin- and single-hose cuffs complicate the movement of patients between bed spaces with different cuff-hose systems. We assessed, using a commercially available noninvasive blood pressure monitor function analyser, the use of single-hose cuffs coupled via a Y-piece adaptor to the twin-hose of noninvasive monitors designed for use with twin-hose cuffs. Assessments were made at three simulated pressures (200/150 mmHg, 120/80 mmHg, and 60/30 mmHg) and at normal and weak arterial pulsations. The use of a single-hose cuff attached with the Y-piece adaptor did not adversely affect the performance of the monitors. PMID- 8214504 TI - A new epidural catheter. Closer eyes for safety? AB - A new design of epidural catheter with three lateral eyes placed in close proximity to its closed end is described. Prototype models of this catheter were tested in 200 obstetric and surgical patients. In a single-blind randomised study it was found to be easy to insert and highly satisfactory in use, when compared to the current catheter type, with three widely spaced lateral eyes. It is hoped that the close spacing of the eyes will eliminate the complication of multicompartment block, as seen with earlier multihole catheters, and improve the safety of epidural block. PMID- 8214505 TI - Evaluation of three portable suction devices. AB - Three portable suction devices were evaluated and compared with a wall-mounted vacuum driven suction unit. The Repro-med Res-Q-Vac, the Drager Sujector 2000 and the Laerdal suction unit were assessed by measuring the time taken to aspirate 140 ml of mock gastric contents. The respective times for each device, expressed as mean and (range) were 7.39 (4.3-10.4), 8.6 (7.8-9.4) and 11.4 (9.4-12.6) s. These compare favourable with the Ohmeda suction unit (7.27 (6.2-8.9)). Each type of device has advantages and disadvantages when factors such as size, power supply and portability are considered, and each will be the most suitable for a particular situation. PMID- 8214506 TI - The anaesthetic management of patients with dystrophic epidermolysis bullosa. A review of 44 patients over a 10 year period. AB - The case notes and anaesthetic charts of 44 patients with dystrophic epidermolysis bullosa were reviewed retrospectively. A total of 390 general anaesthetics were performed for 469 surgical procedures over a 10-year period. Procedures included repair of syndactyly, dilatation of oesophageal strictures, extraction of teeth, excision of skin tumours and other procedures related to dystrophic epidermolysis bullosa. Anaemia, thrombocytosis and hypoalbuminaemia was found in many patients pre-operatively. Damage to skin or mucosa occurred peri-operatively. Four patients developed bullae around the head and neck, two patients developed oral or pharyngeal bullae and three patients developed conjunctival abrasions including one with a new corneal ulcer. There were no reports of laryngeal bullae and no bullae associated with intramuscular injections or the use of limb tourniquets. Thirty-one patients (70%) had evidence of oesophageal strictures and six regurgitated peri-operatively. In all cases there was a history of oesophageal disease. In 10 patients (23%) intubation of the trachea was difficult. It was carried out by various methods including blind nasal and fibreoptic intubation or by using the laryngeal mask airway. One patient requiring a series of general anaesthetics had a tracheostomy formed after fibreoptic intubation. Previous reports have suggested problems with the use of suxamethonium, nondepolarising muscle relaxants and thiopentone. These agents were all used in many of our patients without any adverse effects. There was one intra-operative death in a 35-year-old woman having an oesophageal dilatation which was complicated by oesophageal rupture. PMID- 8214507 TI - The effectiveness of pre-operative advice to stop smoking: a prospective controlled trial. AB - Patients who smoke cigarettes suffer increased postoperative morbidity. A prospective, controlled trial was designed to evaluate the effectiveness of written pre-operative advice to stop smoking before admission for elective surgery and to record the duration of abstinence immediately before the operation. Although the advice was ineffective in persuading patients to stop smoking, it was associated with a reduction in the amount of tobacco consumed. Nicotine and carbon monoxide have important short-term adverse effects but 15% of all patients continued to smoke within an hour of surgery. If patients are unable to give up cigarette smoking completely, it is still worthwhile stopping on admission to hospital. PMID- 8214508 TI - Dural taps revisited. PMID- 8214509 TI - Convulsions following day case anaesthesia. PMID- 8214510 TI - Diathermy and failure of cardiac pacemakers. PMID- 8214511 TI - An inappropriate recommendation for minimising the risk of pacemaker failure during unipolar diathermy. PMID- 8214512 TI - A problem with the Intersurgical Mapleson F breathing system. PMID- 8214513 TI - The laryngeal mask airway in mediastinoscopy. PMID- 8214514 TI - The laryngeal mask airway and intra-ocular surgery. PMID- 8214515 TI - A faulty pulmonary artery flotation catheter. PMID- 8214516 TI - Sickle cell crisis and pain management. PMID- 8214517 TI - Cerebrospinal fluid flashback in spinal needles. PMID- 8214518 TI - Percutaneous versus subconjunctival injection for eye blocks. PMID- 8214519 TI - To cut or not to cut. PMID- 8214520 TI - A problem with the Mallampati sign. PMID- 8214521 TI - Prolonged anaesthesia and carpal tunnel syndrome. PMID- 8214522 TI - An alternative technique for jugular vein catheterisation. PMID- 8214523 TI - Acute organophosphorous insecticide poisoning. PMID- 8214524 TI - Intermediate-like syndrome. PMID- 8214525 TI - Pressurised irrigation. PMID- 8214526 TI - Combined spinal-epidural anaesthesia through the Portex set. PMID- 8214527 TI - Equipment safety checks. PMID- 8214528 TI - Suxamethonium in the deadspace of an adult's indwelling intravenous cannula. PMID- 8214529 TI - Ethyl chloride and venous cannulation. PMID- 8214530 TI - [Recovery of psychomotor and cognitive functions following anesthesia. Propofol/alfentanil and thiopental/isoflurane/ alfentanil]. AB - Recent changes in the medical system have resulted in a significant increase of ambulatory surgical procedures. Therefore, a safe and short postoperative recovery period and, especially, the full recovery of complex psychological function after general anaesthesia have become increasingly important. In the present study we investigated the recovery of psychomotor and cognitive function after general anaesthesia with propofol/alfentanil and thiopentone/isoflurane/alfentanil. PATIENTS AND METHODS. Institutional approval and informed consent was obtained in 40 female ASA I or II patients undergoing diagnostic laparoscopy. As oral premedication the patients received chloracepat (10-20 mg) 45 min before the start of anaesthesia. Anaesthesia was induced in group I with propofol (2.5 mg/kg) and maintained with propofol (6-12 mg/kg/h)/alfentanil (0.05 mg/kg) and 50% N2O in O2. The patients of group II received thiopentone (5 mg/kg) for induction and isoflurane (0.5-1.5 vol%)/alfentanil (0.05 mg/kg) and 50% N2O in O2 for maintenance of general anaesthesia. In particular we measured the following parameters: (1) The recovery time, defined as the interval between the termination of the anesthetic and the patient's correct recall of her birth date. (2) The choice reaction times to optical stimuli (red or green light), which was used as a parameter for attention and psychomotor function. (3) The score in the "Zahlen-Verbindungs-Test" in which the patients had to connect numbers from 1 to 90 in correct order. This is also a parameter to quantify attention and psychomotor function. (4) The digit span which is a value derived from the number of correctly reproduced digits from a list presented to the patients. It is a measure of numerical memory. (5) The Munich Verbal Learning Test, which is the German version of the California Verbal Learning Test. It represents the number of correctly reproduced words from a previously presented list and is a measure of the verbal memory. (6) The Wisconsin Card Sorting Test, which serves to test the ability to plan and act and to form terms and concepts. (7) The State-Trait Anxiety Inventory, to quantify state anxiety. (8) Pain score, using a visual analogue scale. The tests were performed at four measurement points: the day before the operation and 30, 60, and 240 min after recovery. The "Zahlen-Verbindungs-Test", the digit span and the Munich Verbal Learning Test were presented in four parallel forms to minimize learning effects. For statistical analysis of the data the Wilcoxon test was employed within groups and the Mann-Whitney test between groups. RESULTS. The groups were comparable in age, weight, height and level of education. No significant difference was found between them in operation or anaesthesia time or in the total dosage of alfentanil. Recovery time in the propofol group was, at 10 min, significantly shorter than in the isoflurane group, with 16 min. Choice reaction times were significantly increased 30 min after recovery from anaesthesia in both groups. In the propofol group they returned to normal after 60 min, whereas in the isoflurane group significant increases could be observed even 240 min after recovery from the anaesthetic. Choice reaction times were significantly longer in the isoflurane group than in the propofol group 60 min and 240 min after anaesthesia. In the "Zahlen-Verbindungs-Test" the patients showed significantly worse results 30 min and 60 min after anaesthesia. The propofol group tended to be better than the isoflurane group, but the difference did not reach statistical significance. Also in the digit span, the scores were significantly lower 30 min after recovery from the anaesthetic. Here again the propofol group tended to be a little better than the isoflurane group 30 min, 60 min and 240 min after anaesthesia. In the Munich Verbal Learning Test both groups had lower scores 30 min and 60 min, the isoflurane group also 240 min, after recovery... PMID- 8214531 TI - [Ornipressin (POR 8)--effect on coronary blood circulation and the peripheral circulation. An animal experimental study]. AB - Ornipressin (POR 8), referred to below as OR, is a synthetic derivative of natural vasopressin. It was introduced into clinical practice to replace epinephrine as a local vasoconstrictor because OR was presumed to produce fewer undesirable side-effects. However, mayor cardiovascular complications following local infiltration of OR have been reported in recent time. Beside increased blood pressure and changes in heart rate, there is evidence that the systemic effects of OR include a distinct vasopressor activity on coronary arteries. This study was planned to investigate the effects of OR in haemodynamics and the coronary vascular system. METHODS. The effects of OR on systemic haemodynamics and coronary circulation were studied in nine anaesthetized closed-chest mongrel dogs. Anaesthesia was administered using N2O/O2 (FiO2:0.33) and enflurane (1.0 vol% endtidal). Saline-filled catheters were used to measure intravascular pressures. Left ventricular pressure change (dP/dt) was monitored with a tip catheter manometer. Cardiac output (CO) was determined using thermodilution and coronary sinus blood flow, using a Pitot catheter. Recording of baseline values was followed by bolus injection of OR (0.03 U/kg) and changes in haemodynamics were measured for 90 min at fixed time intervals. Statistical analysis was performed by analysis of variance for repeated measures. A value of P < or = 0.05 was considered to indicate statistical significance. RESULTS. Significant maximum changes occurred within 3-5 min after administration of OR. Systolic and diastolic arterial pressures increased by 33% and 39%, respectively. With only minor changes in heart rate, cardiac output markedly decreased by 44% and total peripheral resistance increased by 159%. Impaired pump function of the left ventricle became obvious by a decrease in maximum dP/dt, a decrease in ejection fraction by 35%, and a concomitant sharp increase in left ventricular enddiastolic pressure by 68% and in endosystolic volume by 41%. At the same time, OR produced a marked impairment of coronary perfusion. Myocardial blood flow fell by 32%, while coronary vascular resistance rose by 112%. Increased myocardial oxygen demand and reduced oxygen supply resulted in very low values of coronary venous oxygen saturation (< 20%). CONCLUSIONS. Systemic effects of OR are characterized by a sharp rise in arterial blood pressure. Concomitantly a decrease of myocardial contractility leads to a compromised left ventricular function with marked increases in left ventricular enddiastolic pressure. These haemodynamic changes are associated with an imbalance of myocardial oxygen demand and delivery due to the distinct OR-induced coronary constriction. With regard to the deterioration of systemic and cardiac haemodynamics the indications and use of ornipressin in clinical practice need to be reevaluated. PMID- 8214532 TI - [Ropivacaine 1% versus bupivacaine 0.75% without a vasoconstrictor. A comparative study of epidural anesthesia in orthopedic surgery]. AB - The long-acting local anaesthetic agent ropivacaine, S(-)-1-propyl-2',6' pipecoloxylidid, is characterised by lower lipid solubility and lower cardiotoxicity compared with bupivacaine. This study was designed to evaluate its clinical efficacy and motor blocking properties when using lower volumes and higher concentrations of both plain substances. METHODS. In a randomised, double blind study plain ropivacaine (ro) 1% (150 mg) and bupivacaine (bu) 0.75% (112.5 mg) were compared in 44 patients. In the lateral position, epidural anaesthesia was performed at L2/3 or L3/4 using the loss-of-resistance technique. A test dose of 3 ml was given followed by 12 ml (total volume 15 ml). Sensory blockade was registered by the pin-prick method after 2 min at 5-min intervals up to maximal levels and after the operation at 30-min intervals. Simultaneously, the motor block was determined by means of the Bromage scale. Results are given as median values. RESULTS. The onset of analgesia was 6.0 min for both substances (L2), the time to level L5 16.0 and 17.0 min, respectively. The median maximum upper level of sensory analgesia was achieved after 24.5 min with ro (Th 5) and after 21.0 min (Th 7) with bu. The maximum durations (regression to L2) were 321.5 (ro) and 266.0 min (bu) (P < 0.05). Times for 2-segment regression were comparable at 177.5 and 176.0 min, respectively, and for 4-segment regression at 201.3 and 222.0 min. Twenty-one of the 22 patients developed a first-degree motor block (latency 15 and 12 min); 16 patients in the ro group developed a second-degree block, as did 14 in the bu group (latency 24 and 22 min). Third-degree motor block was recorded in 3 patients (latency 45 and 38 min). The duration of first degree motor block was 233 min and 207 min, of second-degree block 150 and 155 min, and third-degree block 135 min in both groups. The mean arterial pressures and heart rates did not differ. The diastolic pressures were lower after bu ( 8.3%) than after ro (-0.4%) at 30 min. No major side effects were observed. Theodrenaline and/or dihydroergotamine (1:10 diluted) was administered to 38.6% of the patients; 34.1% received atropine for the treatment of bradycardias (decrease > or = 12%) and hypotension of more than 20%. No significant differences were found in frequency of analgesia (pin-prick) between both groups. One of 22 patients in the ro group and 6 of 22 in the bu group required additional analgesics or general anaesthesia. The difference is not statistically significant, but is of clinical relevance. With 2 patients after ro and 4 patients after bu the relaxation was insufficient for good operating conditions. CONCLUSION. Ropivacaine 1% produced a longer duration of analgesia and better clinical efficacy than bupivacaine 0.75%. The clinical difference in motor blockade was not statistically significant. The Bromage scale is not representative for a substance with good analgesic effects and moderate motor blocking properties, as has been shown in sophisticated studies on ropivacaine motor blockade. PMID- 8214533 TI - [Modification of oxygen consumption following major abdominal surgery by epidural anesthesia]. AB - In the postoperative period patients are at risk of excessive oxygen consumption (VO2). However, patients suffering from cardiovascular disease may be unable to increase their oxygen transport capacity sufficiently and may be especially vulnerable to tissue hypoxia as part of the reaction to intraoperative stress. During the last 10 years conflicting results concerning the benefits of a combined epidural and light general anaesthesia have been published. Some of the results indicate that postoperative catabolism may be depressed and that the neuroendocrine response to stress may be inhibited by such a combined technique. We studied the effect of a combined epidural and light general anaesthesia on VO2 in the early post-operative period. PATIENTS AND METHODS. Three groups of patients were studied: group 1 contained 10 patients scheduled for major urological procedures of at least 3 h duration who received a combined epidural and light general anaesthesia. Group 2 contained 17 patients with procedures comparable to group 1 but received a standard general anaesthesia with isoflurane, N2O and fentanyl. In addition, 13 patients undergoing minor urological procedures of less than 2 h duration and undergoing standard general anaesthesia were included in the study as a control group (group 3). All patients gave informed consent. Preoperative management was the same in the three groups. Perioperative risk was assessed according to the ASA classification. In group 1 patients, an epidural catheter was placed preoperatively at the L3/4 interspace and tested for correct positioning using 4 ml of 2% mepivacaine with epinephrine 1:200,000. After induction of anaesthesia an epidural block was established with 0.5% bupivacaine for intraoperative analgesia and 0.25% bupivacaine for postoperative pain relief. The initial dosage was determined (according to Bromage's method) to reach a sensory level of T-6. Two-thirds of the initial dose was the given on two occasions, each 90 min after the dose before. End-tidal isoflurane concentrations ranged between 0.3 and 0.6 vol% in this group. In groups 2 and 3, endtidal isoflurane concentrations of 1.0 to 1.5 vol% were applied. Postoperative analgesia was achieved in these groups using repeated doses of 7.5 mg piritramide i.v. Oxygen consumption was measured in the recovery room using the Deltatrac (Datex) metabolic monitor. Measurements were performed with a canopy room air dilution technique. Arterial oxygen saturation of the patients was monitored continuously using pulse oximetry. Data acquisition was started within 10 min after extubation and continued for at least 60 min until a steady state of oxygen consumption was reached. We recorded the average VO2 during the initial 5 min of the measurement period and during another 5-min period after the steady state was reached (45-60 min after extubation). RESULTS. Patients in the three groups were comparable in age, height and body weight (Table 1). The duration of procedures in groups 1 and 2 ranged between 4 and 7 h. Groups 1 and 2 were further comparable in terms of intraabdominal procedures, intraoperative blood loss, fluid replacement, and fall in body temperature during the operation (Table 2). Heart range was significantly higher in group 2 during the 5-min test interval (Table 3). Figure 1 shows the typical course of oxygen consumption in patients of groups 1, 2, and 3. The readings in the group 1 patient as well as in the group 3 patients were stable throughout the observation period. Oxygen consumption was in the physiological range. In contrast, in the group 2 patients during the early postoperative period, increased values of VO2 (approx. 50% above normal) were observed. These findings were highly significant in our study. In the early postoperative period (5 min) patients in group 1 showed a VO2 or 3.6 +/- 0.4 ml.kg-1.min-1. This was the same as in group 3 (3.5 +/- 0.3 ml.kg-1.min-1). In contrast, in group 2 a VO2 of 5.3 +/- 0.7 ml.kg-1.min 1 PMID- 8214534 TI - [The bactericidal effect of oxybuprocaine. A possible cause of false negative results in bronchoalveolar lavage]. AB - New approaches in the diagnosis of pneumonia, especially in intensive care units, are quantitative cultures of bronchoalveolar (BAL) fluid or the protected specimen brush. The sensitivity of these methods, however, has often been found to be as low as 50-60%. One possible explanation for the low sensitivity of these diagnostic tools is the antimicrobial activity of local anaesthetics used in bronchoscopy. Therefore, we investigated the bactericidal properties of oxybuprocaine, a topical anaesthetic used for bronchoscopy in our clinic, in order to test the reliability of specimens obtained from BAL. METHODS. The bactericidal activity of oxybuprocaine in concentrations of 1%, 0.1%, 0.05% and 0.01% was tested by constructing time-kill curves for Streptococcus pneumoniae, Hemophilus influenzae, Pseudomonas aeruginosa and Escherichia coli. Five stains of each bacterial species were tested. The inoculum size was 10(4) ml, and bacteria were counted after 10, 20, 30, 60 and 120 min. RESULTS. The resulting time-kill curves are demonstrated in Figs. 1-4. The most sensitive bacteria were S. pneumoniae and H. influenzae, in which significant bactericidal activity could be shown even with a 0.01% solution of oxybuprocaine. E. coli and P. aeruginosa were also inhibited, but only at the highest concentration of 1%. CONCLUSIONS. The use of local anaesthetics before material is taken for culture, e.g. from BAL, may give rise to false-negative results and should therefore be avoided or reduced. For each local anaesthetic used in bronchoscopy, the concentrations that can be used without the risk of false-negative results should be determined. PMID- 8214535 TI - [Organizational forms of emergency medicine in international comparison]. AB - The tasks of preclinical emergency medicine systems (PEMS) are to stabilize and maintain the vital functions and to guarantee qualified transport to the hospital. Worldwide, different structures exist as a result of historical developments. Legal regulations for PEMS have been introduced in most of the industrialized countries since 1960. More and more aspects have been subject to detailed regulations. PEMS are provided either by state-owned or by state controlled (private) organisations. In most of the "underdeveloped" countries legal regulations do not exist and PEMS is often provided by social workers, by the army or by volunteers. In most countries, PEMS are financed by the state with a charge on the patient. In a few states PEMS are totally financed by the public health structure. Modern PEMS are controlled from dispatch centres which receive emergency calls (mostly by telephone) and send the appropriate rescue unit. In most states the staff of dispatch centres are paramedics; in some countries and in some urban areas physicians control the dispatch centre. In PEMS without physicians on the scene, an information exchange between the scene and the hospital can be observed frequently, in contrast to systems with physicians on the scene. Worldwide, ground-based PEMS are preferred, but in most countries an additional air rescue system has been established. The quality and quantity of the technical equipment of the ground-based PEMS differ widely: nationwide regulations exist, however, in the USA and Germany. Generally, there are two main concepts concerning the personnel structure: PEMS are either physician based or not. Requirements for emergency physicians differ greatly: in some countries no formal requirements exist, in others extensive practical and theoretical training is required.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214536 TI - [Anesthetic gas consumption and costs in a closed system with the PhysioFlex anesthesia equipment]. AB - A marked decrease in both personal and environmental pollution with anaesthetic gases as well as in costs is possible with anaesthesia machines which can be run with a low fresh gas flow (FGF) [9]. Low-flow anaesthesia can be performed with appropriately equipped circle systems, although strongly reduced FGF minimises the control of depth of anaesthesia and gas concentrations. Microprocessor controlled feedback systems allow the utilisation of closed-circuit systems throughout the whole duration of anaesthesia, maintaining full anaesthetic control [3,5]. The aim of this investigation was to determine the costs resulting from gas consumption and clinical suitability of the recently marketed PhysioFlex anaesthesia machine. METHODS. We used a PhysioFlex (Physio, Hoofdorpp, Netherlands) in a series of 15 routine otorhinolaryngological interventions. After induction with thiopentone and suxamethonium, general anaesthesia was maintained with nitrous oxide in 30% oxygen and isoflurane and supplemented with fentanyl and atracurium. The expenditure of anaesthetic gases was recorded during a total of 61 h and 27 min and differentiated into its components. Anaesthetic gas uptake and costs were compared with different breathing systems (low-flow anaesthesia, semiclosed system and non-rebreathing system) under similar clinical conditions. RESULTS. The average minute volume was 6.84 (+/- 1.17) l and the expiratory isoflurane concentration was 0.91% (+/- 0.14%) (Table 1). These settings resulted in an oxygen expenditure of 27.9 (+/- 8.46) l/h with total costs of SFr. 0.04, nitrous oxide 11.9 (+/- 5.4) l/h and 0.27, isoflurane 3.9 ml/h and SFr. 5.42. In contrast, other breathing systems in analogous settings resulted in greater costs by a factor of 0.77 for low-flow anaesthesia (FGF 1 l/min), 2.47 for a semiclosed system (FGF 3 l/min) and 5.63 for a valve controlled non-rebreathing system (FGF 6.84 l/min) (Table 2). DISCUSSION. The emission of anaesthetic gases can be lowered by measures that avoid unintended gas fallout, the application of filters, scavenging systems and efficient air circulation in operation and recovery rooms [8]. Above all, the use of the lowest possible FGF is advantageous for the patient insofar as better conditioned breathing gases are available, and economic and environmental effects are more significant (Table 3). With the method of quantitative anaesthesia as performed by the PhysioFlex, it is now possible to reduce gas expenditure according to the requirements of the patient as well as maintaining full control of anaesthesia depth. Simultaneously, multiple secured feedback control systems guarantee adequate monitoring and storage of respiratory and metabolic parameters. The duration of nitrous oxide wash-out can be a problem, in particular, when a changeover to O2/air is required. PMID- 8214537 TI - [Use of the laryngeal mask in difficult intubation]. AB - Although the incidence of difficult airway is very low, involving less than 1% of all patients, failed air-way management is the main cause of mortality or serious morbidity during anaesthesia. Successful management of a difficult airway starts with recognition of the potential problem. A careful preoperative history and clinical examination should elicit obvious problems to allow prediction of a potentially difficult airway. Besides the introduction of different instruments and techniques, the laryngeal mask (LMA) has been suggested to be effective both in when difficult airway is known in advance to be present and after failed intubation. CASE REPORT. The use of the LMA in a patient scheduled for endoscopic resection of a ureteral stone as day surgery is described. The patient presented reduced mobility of the atlanto-occipital joint, temporomandibular ankylosis (mouth opening of 1.9 cm), dislocated teeth, and kyphosis of the thoracic spine. Due to deformation of the spine, the patient was placed in a half-sitting position (30 degrees). Anaesthesia was induced with fentanyl (1.5 micrograms.kg 1) and propofol (2 mg.kg-1). Although the conditions made it difficult to manage the patient's airway, the LMA was inserted without complications or trauma. Anaesthesia was maintained with isoflurane and nitrous oxide in oxygen. After 1.5 h of assisted ventilation the LMA was removed when the patient opened his mouth on request. DISCUSSION. Significant advances in the management of the difficult airway have been achieved in recent years. However, avoidable deaths on intubation have been attributed to unexpected difficulties and poorly managed situations. Thus every anaesthetist should be prepared for potential difficulties by training and be able to follow a rational plan of action. If despite all manoeuvres a tracheal tube cannot be passed, a failed intubation drill must be instituted, and if oxygenation is still not possible a failed ventilation drill must be followed. The LMA is a new device developed to provide an airway for anaesthesia. However, since the LMA can be inserted quickly and blind, it can be used as an alternative airway in patients in whom the trachea is difficult to intubate. The lower incidence of post-operative complications than with endotracheal intubation is a further advantage, particularly during anaesthesia for day surgery. PMID- 8214539 TI - [ST trend analysis. Monitoring of risk patients?]. AB - ST-segment monitoring has been proved to be an effective tool in detecting silent myocardial ischaemia, which is an important factor for perioperative cardiac morbidity. The case of a 72-year-old patient with peripheral vascular disease who underwent iliaco-femoral bypass surgery due to acute occlusion of a existing femoropopliteal bypass is reported. As part of a study the patient had perioperative ST-segment holter monitoring which showed pre-, peri- and postoperative severe episodes of silent myocardial ischaemia. No episode was accompanied by anginal symptoms. Post-operatively, a long-lasting episode of severe ST-segment deviation with complex arrhythmias occurred, resulting in cardiac failure and lung oedema. This ST-segment deviation began when the surgical procedure had been concluded and the patient extubated. The peak of the deviation occurred during transport from the operating room the recovery room. The existing ECG changes and the raised heart rate, from the beginning of the time in the recovery room to arrival on the normal ward, were not adequately recognized. The lack of clinical symptoms was misinterpreted. Many hours before, ST deviations and higher heart rate could be seen as precursors of a severe cardiac event. This demonstrates the importance of silent ischaemia in the perioperative period and shows the usefulness of ECG monitoring, especially of the ST segment, in detecting silent ischaemia and enabling early treatment. PMID- 8214538 TI - [Postoperative air embolism caused by pneumatocephalus following occlusion of the posterior fossa. A rare complication indicative of a bridging vein disruption]. AB - Many neurosurgeons prefer the sitting position for patients undergoing surgery in the posterior fossa because of the easier access and better conditions for haemostasis. Pneumatocephalus is a possible consequence of surgery in the posterior fossa with the patient in the sitting position. When this occurs air may enter the subarachnoid space, the cisternae, the ventricular system or the subdural space; it becomes more likely when any of the following is/are present: loss of CSF, a large cavity resulting from surgery, external or internal drainage of CSF, osmotic diuresis, and hyperventilation. Distances of 1-2 cm between cranium and brain may be found. The rupture of bridging veins may cause a subsequent subdural haematoma. Air embolism due to pneumatocephalus via the same vein after closure of the cranium is in this paper for the first time. Case report. A 37-year-old man with known Hippel-Lindau disease presented for posterior fossa surgery for treatment of a haemangioblastoma of the right cerebellar hemisphere. Surgery was done with the patient in a sitting position. Apart from one short episode of air embolism without haemodynamic changes no intraoperative complications occurred. After closure of the cranium and galea an unexpected and inexplicable air embolism of 10 min duration occurred again. TEE demonstrated the air looking like a string of beads in the right atrium. As complete skin had already been closure no explanation for the air embolism could be found. The patient was positioned supine, and air was no longer detectable in the right heart after 1 min. Approximately 1 h later both pupils were dilated and unreactive to light.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214540 TI - [The clinical picture and therapy of septic shock]. AB - This special article for continued education begins with a broad definition of septic shock. The following section describes the fundamental organ dysfunctions and pathomechanisms. The different pattern of septic shock and a clearly defined therapeutic concept are also offered. The specific therapeutic interventions (only those which have been proven effective and recommendable for routine clinical use) will be presented. Monitoring of infection and organ function are discussed briefly. PMID- 8214541 TI - Anaesthesia in rural general practice. PMID- 8214542 TI - Intensive care utilisation: the Baragwanath experience. AB - Intensive care medicine is an expensive service whose impact on health care has been questioned. South Africa is a country undergoing rapid social and political change and the role of intensive care medicine in the health care system of this country needs to be assessed. In this paper we evaluated the quality, cost effectiveness and utilisation of technology in the intensive care unit of Baragwanath Hospital, a hospital serving the black community of Soweto. PMID- 8214543 TI - Cranial computed tomography in the assessment of neurological complications in critically ill patients with systemic lupus erythematosus. AB - The cranial computed tomography findings in 22 critically ill patients with systemic lupus erythematosus in the intensive care unit were reviewed to document the spectrum of pathology encountered and to assess the contribution of cranial computed tomography to the diagnosis and management of such patients, many of whom had severe multisystem disease. Thirty-one scans were performed in 22 patients, all of which were abnormal. Premature cerebral atrophy was identified in fifteen patients (68%), cerebral infarction in five (23%), intracranial haemorrhage and cerebral oedema in four each (18%), and hydrocephalus in three (14%). Six patients had multiple pathologies. The cranial computed tomography findings confirmed the clinical diagnosis in 13 of 22 cases (59%) and altered it in nine (41%). The contribution to diagnosis and management justifies transportation and computed tomography scanning. The contribution to patient outcome, however, is uncertain as mortality was 91%. PMID- 8214544 TI - The systolic blood pressure variation as an indicator of pulmonary capillary wedge pressure in ventilated patients. AB - Animal data have suggested that the systolic pressure variation (SPV) noted during positive pressure ventilation may be a sensitive indicator of hypovolaemia. The aim of this study was to correlate the SPV with the pulmonary capillary wedge pressure (PCWP) in a heterogeneous group of ICU patients on volume-cycled ventilation. Three hundred data sets were collected on 226 patients. The correlation coefficient between the SPV and PCWP for the first half of the data set was -0.84 (P < 0.001). The linear regression formula from this data set was: PCWP = 20-(SPV*0.7). Using this formula the predicted PCWP was then correlated with the measured PCWP using the second half of the data base. The correlation coefficient was 0.87 (P < 0.001). The correlation coefficient between the SPV and PCWP for the entire data base (300 observations) was -0.86 (P < 0.001). It is concluded that analysis of the arterial pressure tracing may be useful in estimating the pulmonary capillary wedge pressure in ventilated patients. PMID- 8214545 TI - End-tidal oxygen measurement compared with patient factor assessment for determining preoxygenation time. AB - Time to adequate preoxygenation was assessed in 200 elective surgical patients, using measurement of end-tidal oxygen concentration. A variety of patient factors were assessed as to their ability to predict the time required to preoxygenate a patient. Of the 200 patients, 23 (11.5%) were unable to be adequately preoxygenated; most of these cases were due to a poor mask fit. The average time for preoxygenation was 154 seconds (range 43-364 seconds). Of those patients who could be preoxygenated, 46 (23%) required more than three minutes. Although a regression equation could be constructed to calculate time required for preoxygenation, the wide standard errors of the coefficients preclude a clinically useful predictive equation. We thus found that we could not accurately predict time required for preoxygenation and that a routine three minutes preoxygenation may not be sufficient for many patients. However, the measurement of end-tidal oxygen concentration is a very useful method of determining the end point for preoxygenation. PMID- 8214546 TI - "Whoosh" test as a teaching aid in caudal block. AB - Fifty-three patients presenting for minor gynaecological procedures received caudal blocks performed by residents. These residents used the standard technique which relied on the "give" felt as a needle penetrates the sacrococcygeal membrane and the loss of resistance to air when the needle is correctly placed. The "whoosh" test was noted by the supervising anaesthetist who did not reveal his findings to the residents. A positive test consisted of a characteristic "whoosh" sound on auscultation of the thoracolumbar region when 2 to 3 ml of air was injected into the caudal extradural space. The predictive value of a positive test was found to be 78%, 80.7% and 97.7% (P < 0.01) for a positive "give", loss of resistance and "whoosh" test respectively. Negative tests had no predictive value for "give" and loss of resistance whilst the predictive value of an absent "whoosh" was 100% (P < 0.05). Thus we conclude that the "whoosh" test is an excellent aid in the teaching of caudal anaesthesia. PMID- 8214547 TI - Analgesia after caesarean section with intramuscular ketorolac or pethidine. AB - We compared, in a double-blind randomised study, intramuscular ketorolac 30 mg (n = 49) and intramuscular pethidine 75 mg (n = 51) for analgesia after elective caesarean section under general anaesthesia. Anaesthesia was induced with thiopentone and suxamethonium and maintained with atracurium, nitrous oxide and isoflurane. Intravenous fentanyl 100 micrograms was given after delivery of the neonate. In the recovery ward, patients who requested analgesia were allocated randomly to receive ketorolac 30 mg or pethidine 75 mg intramuscularly. Analgesia was assessed at intervals up to six hours, using a visual analogue scale and a four-point verbal scale, while duration of analgesia was taken as the time until the patient requested additional analgesia. There was no difference in the duration of analgesia between groups (Mann-Whitney test P = 0.27, Mantel Haentszel test P = 0.17). Twenty-six patients in the ketorolac group and 17 patients in the pethidine group requested further analgesia by 90 minutes. However, four patients in the ketorolac group and six patients in the pethidine group requested no further analgesia within 24 hours. Pain VAS and overall assessment of analgesia was similar between groups, although more side-effects (nausea, dizziness) were noted in the pethidine group. Ketorolac 30 mg and pethidine 75 mg provided similar but variable quality of analgesia after caesarean section. PMID- 8214549 TI - Acute normovolaemic haemodilution and idiopathic scoliosis surgery: effects on homologous blood requirements. AB - After the introduction of acute normovolaemic haemodilution(NVHD) in our hospital, we prospectively studied 19 patients managed with moderate NVHD (mean haematocrit 0.28, SD 0.02) during idiopathic scoliosis surgery (mean angle 53.2, SD 16.7 degrees) with the Cotrel-Dubousset instrumentation (CDI). Our standard scoliosis anaesthetic technique was used. Intraoperatively, one patient received one unit of homologous blood. Postoperatively, seven patients received ten units of homologous blood. Homologous blood used was reduced by about 83% for this procedure in our institution. In the assessment of fluid and blood requirements we found physical signs reflecting tissue perfusion and oxygen supply more reliable than the estimated blood loss using the suction bottle and swabs. The similar postoperative complications (nine fever, five atelectasis/pneumonia, one urinary infection, one phlebitis), anaesthetic duration (mean 5.21, SD 1.13) hours, hospitalisation (mean 6.67, SD 1.19) days and return to normal activity (mean 8, SD 7.68) weeks indicate that the NVHD patients did just as well as with our previous regimen when only homologous blood was used. PMID- 8214548 TI - A comparison of caudal epidural bupivacaine with adrenaline and bupivacaine with adrenaline and pethidine for operative and postoperative analgesia in infants and children. AB - This study compares the effectiveness of two drug combinations--(a) bupivacaine with adrenaline and (b) bupivacaine with adrenaline and pethidine--on operative and postoperative pain relief when administered by the caudal route in infants and children. A randomised controlled trial was conducted on fifty children below the age of twelve years: 25 children were randomly allocated to each group. Both groups had a significant period of analgesia in the postoperative period. None of the children in either group required parenteral analgesia. Though the group with pethidine had a longer duration of analgesia and sedation, the very high incidence of vomiting and delay in urination observed in this group would preclude the use of pethidine routinely. No respiratory depression was seen in either group. PMID- 8214550 TI - Education for general practitioners proposing to administer anaesthesia in rural general practice. PMID- 8214551 TI - Anaesthetists and euthanasia. PMID- 8214552 TI - The baron and severe sepsis--a clinical model of self-induced endotoxaemia. PMID- 8214553 TI - Anaesthesia for aortoesophageal fistula. PMID- 8214554 TI - Diathermy and the telectronics "META" pacemaker. PMID- 8214555 TI - Neurological damage resulting from extracorporeal shock wave lithotripsy when air is used to locate the epidural space. PMID- 8214556 TI - Ludwig's angina causing respiratory arrest in the Solomon Islands. PMID- 8214557 TI - Propofol i.v. for intrathecal pethidine-induced pruritus. PMID- 8214558 TI - Ondansetron in theophylline overdose. PMID- 8214559 TI - Use of a size 2 LMA to relieve life-threatening hypoxia in an adult with quinsy. PMID- 8214560 TI - Temperature gradient down the oesophagus? PMID- 8214561 TI - Reaction to ketorolac. PMID- 8214562 TI - Neuroleptic malignant syndrome and malignant hyperthermia. PMID- 8214563 TI - Lack of extrapyramidal side-effects from droperidol in low dose. PMID- 8214564 TI - Analgesia after VTOP. PMID- 8214565 TI - Complication of arm abduction. PMID- 8214566 TI - Intra-arterial injection of propofol. PMID- 8214567 TI - Medical involvement in the recovery room. PMID- 8214568 TI - An unusual reason for cancellation of day case surgery. PMID- 8214569 TI - Convulsion during lignocaine infiltration. PMID- 8214570 TI - Automated allyl cleavage for continuous-flow synthesis of cyclic and branched peptides. AB - An automated allyl cleavage scheme on a continuous-flow peptide synthesizer was used for the preparation of "head-to-tail" cyclic peptides, branched peptides, and multiple antigenic peptides. Standard allyl removal uses a suspended palladium catalyst. This approach is not feasible on a batch and continuous-flow peptide synthesizer due to problematic delivery of the insoluble palladium catalyst. Solvent conditions were examined and optimized to solubilize the catalyst, prevent undesired Fmoc deblocking and be compatible with sensitive amino acids (Trp and Met) and with glyco- and sulfopeptides. Protocols for a continuous-flow peptide synthesizer were modified using new conditions to carry out the allyl cleavage scheme for the facile preparation of complex peptides. PMID- 8214571 TI - Determination of p-nitrophenol hydroxylase activity of rat liver microsomes by high-pressure liquid chromatography. AB - p-Nitrophenol hydroxylation to p-nitrocatechol is a useful metabolic marker for the presence of functional cytochrome P450 2E1 in mammalian cell microsomes, but the assay is limited by the sensitivity of the spectrophotometric method used to monitor p-nitrocatechol formation. In this paper, a reverse-phase high-pressure liquid chromatography method, which is nearly 20 times more sensitive than the spectrophotometric method and more specific for p-nitrocatechol determination, is described. The method involves monitoring the presence of p-nitrocatechol in the trifluoroacetic acid-quenched reaction mixtures at 345 nm. The utility of the method was demonstrated with rat liver microsomes, where p-nitrocatechol formation was found to be NADPH dependent, was linear with incubation times (2.5 to 30.0 min) and protein concentrations (0.03-0.48 mg/incubation), and exhibited typical Michaelis-Menton kinetics (Km = 197 microM, Vmax = 2.8 nmol/mg protein/min). PMID- 8214572 TI - The use of high-performance electrophoresis chromatography for the micropurification of cerebrospinal fluid proteins in the rat. AB - Using reversed-phase high-performance liquid chromatography (HPLC) on a Vydac C8 column in conjunction with sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) and silver staining, we have identified more than 30 proteins in cerebrospinal fluid collected from adult rats by cannulation of cisterna magna. When these partially purified cerebrospinal fluid proteins were further fractionated by high-performance electrophoresis chromatography (HPEC) on an Applied Biosystems 230A HPEC system using a 10% T SDS-polyacrylamide gel with a phosphate base running buffer system under nonreducing conditions, we have purified more than 10 proteins to apparent homogeneity from a pool of 10 ml of rat cerebrospinal fluid as verified by silver staining and direct N-terminal amino acid sequencing. Two additional series of experiments using rat cerebrospinal fluid over a 12-month period yielded virtually identical results. A major advantage of HPEC over conventional HPLC is that the recovery of protein is almost quantitative and is in the range of 90-95% using as little as 1 microgram of protein. The purified proteins from HPEC are ready for direct protein sequencing following a buffer exchange to remove residual Tris and phosphate without additional manipulation. The potential use of HPEC for micropurification of proteins was discussed. PMID- 8214573 TI - Arsenical-based affinity chromatography of vicinal dithiol-containing proteins: purification of L1210 leukemia cytoplasmic proteins and the recombinant rat c-erb A beta 1 T3 receptor. AB - Proteins containing vicinal dithiols were purified by affinity chromatography using Sepharose 4B linked to aminohexanoyl-4-aminophenylarsineoxide (As Sepharose). The protein vicinal dithiols form stable dithioarsine derivatives with the arsine oxide moieties of the gel. The adsorbed proteins were eluted, at physiological pH, by buffers containing beta-mercaptoethanol or dithiothreitol. The dithiol proteins were identified by their specific labeling with N-iodoacetyl 3-[125I]-iodotyrosine. Cytoplasmic thiol proteins of L1210 murine leukemia lymphoblasts were separated into three classes by interaction with As-Sepharose. Proteins that did not bind to the gel consisted of monothiol proteins; proteins eluted by beta-mercaptoethanol include vicinal dithiol-containing proteins with low affinity for the arsine oxide. DL-Dithiothreitol (DTT) elutes a large group of vicinal dithiol-containing proteins with high affinity for the arsine groups. Gradient elution allowed characterization of the relative affinities of dithiol proteins for the As-Sepharose. A one-step purification of the L-triiodothyronine recombinant rat c-erb A beta 1 T3 receptor synthesized in yeast required pretreatment with DTT for binding to As-Sepharose and resulted in a 62-fold increase in specific activity. The procedure allows purification of proteins inhibited by phenylarsine oxide such as phosphotyrosine phosphatases, proteins that are subject to redox regulation, and dithiol proteins that are targets of oxidative stress. PMID- 8214574 TI - Development and optimization of reactivation techniques for carbamate-inhibited brain and plasma cholinesterases in birds and mammals. AB - Two biochemical assays were developed which promote and measure the induced reactivation of carbamate-inhibited cholinesterases in avian and mammalian brain and plasma samples. The effects of inhibitor concentration, temperature, and the extent of dilution on the achievement of a steady state equilibrium and the subsequent level and rate of recovery of brain cholinesterase activity were investigated. A similar procedure for reactivation of carbamate-inhibited plasma cholinesterase activity involved the removal of excess carbamate from a small sample volume (< 400 microliters). Both methods begin by measuring cholinesterase activity immediately following dilution and involve an incubation period during which conditions for spontaneous reactivation of the inhibited enzymes are maximized. Both assays are suitable for large-scale, rapid use and appear able to restore inhibited cholinesterase activity to levels closely approximating that of control values for each species tested. These methods will not only maximize the usefulness of cholinesterases in monitoring carbamate pesticide exposure but should prove to be extremely useful tools in the forensic assessment of carbamate exposure in human and wildlife pesticide incidents. PMID- 8214575 TI - Compositional analysis of peptidoglycan by high-performance anion-exchange chromatography. AB - A high-performance anion-exchange chromatography method with pulsed-amperometric detection has been developed for the simultaneous analysis of both amino acids and amino sugars and applied to the compositional analysis of peptidoglycan hydrolysates. Chromatography of the acid hydrolysis products was performed on a CarboPac PA-1 anion-exchange column, with pulsed-amperometric detection. Complete resolution of the two amino sugars (glucosamine and muramic acid) and eight of the nine amino acids (Ala, diaminobutyric acid, diaminopimelic acid, Glu, Gly, homoserine, Lys, Orn, and Ser) known to occur in various peptidoglycans was achieved within 70 min. Only homoserine and glycine (retention times 26.8 and 26.9 min, respectively) were not resolved by this procedure, but the simultaneous occurrence of these two amino acids in peptidoglycan is extremely rare. Reproducibility of the separations was shown to be very high and detection limits exceeded 10 pmol for glucosamine. This convenient and simple analysis was applied to the quantitation of many crude peptidoglycan samples isolated from the species of the Proteeae (Proteus, Providencia, and Morganella) for the determination of the extent of peptidoglycan O-acetylation. PMID- 8214576 TI - High-resolution liquid chromatography of oligonucleotides on nonporous alkylated styrene-divinylbenzene copolymers. AB - Phosphodiester-oligonucleotides were separated by ion-pair reversed-phase HPLC on nonporous polystyrene-based particles having a diameter of 2.1 +/- 0.12 microns. With unmodified poly(styrene-divinylbenzene) beads it was not possible to resolve oligonucleotides efficiently. However, upon addition of polyvinyl alcohol during polymerization baseline resolution of phosphorylated oligodeoxyadenylic acids with a chain length of up to 30 bases was obtained, with triethylammonium acetate serving as ion-pairing reagent. An even higher separation efficiency was achieved by Friedel-Crafts alkylation of poly(styrene-divinylbenzene) particles. At a column temperature of 50 degrees C, the number of theoretical plates exceeded 6 x 10(5) per meter. The maximum loading capacity for a 50 x 4.6-mm i.d. column still resulting in the highest resolution was 0.1 microgram. Calibration curves showed excellent linearity over a range of at least 4 magnitudes, with a lower mass detection limit of 0.16 ng. Recoveries ranged from 96.7 to 100.8%. The same stationary phase also allowed the separation of phosphorylated from dephosphorylated oligonucleotides, the former ones being eluted earlier. PMID- 8214577 TI - A spectrophotometric assay for nitrate using NADPH oxidation by Aspergillus nitrate reductase. AB - An assay based on the oxidation of NADPH during the enzymatic conversion of nitrate to nitrate by Aspergillus nitrate reductase [EC 1.6.6.2] was developed for specific quantification of nitrate. This spectrophotometric method was used to measure nitrate present in human urine, human serum, and tissue culture medium. Used as a kinetic assay, the method exhibited (1) linearity over a range of 1.25 to 40 microM nitrate, (2) an upper sensitivity of 20 microM, (3) a lower sensitivity of 1.25 microM nitrate, and (4) intraday and interday variability ranging from 0.6 to 6.1%. To judge the acceptability of this method as a kinetic assay, we determined the Km for Aspergillus nitrate reductase to be 199 microM. The Km was based on analyzing three separate lots of commercially purified enzyme. Mean nitrate content of eight urine specimens analyzed by this assay (1111 microM) was not significantly different from that determined by a chemiluminescence method (1144 microM). Analysis of serum using the two methods showed mean nitrate concentrations of 23 and 36 microM, respectively. Based on serial dilutions of serum, the lower nitrate content of serum observed with nitrate reductase assay could not be explained by the presence of inhibitors. Rat pulmonary alveolar macrophages were induced to produce nitric oxide which oxidizes to nitrite and nitrate. Nitrite and nitrate present in tissue culture medium of unactivated and activated macrophages were in proportion to total nitrogen oxides (NO(x)) determined by the chemiluminescence method. We conclude that the Aspergillus nitrate reductase assay is an accurate spectrophotometric method for determining nitrate content of human urine and tissue culture supernatants. PMID- 8214578 TI - Compact protein sequencer for the C-terminal sequence analysis of peptides and proteins. AB - We describe the construction of a compact protein sequencer designed specifically for the C-terminal sequence analysis of peptides and proteins. This sequencer has a vertical flow path and is equipped with a continuous flow reactor (CFR). The flow paths for the various reagents and solvents have been minimized. A unique feature of this instrument is the design of a quadrate valve (quad valve) which permits the delivery of four solvents or reagents to the conversion flask (CF). Combination of two of these quad valves in series permits the delivery of eight solvents and reagents to the CFR. The CF contains three inputs from the top, one for transfer of the contents of the CFR, one which is used as a vent, and one for input of solvents or reagents from the CF quad valve. The CF drains from the bottom, connecting to a switching valve which allows delivery either to a waste bottle or to an on-line HPLC. Another unique feature of this instrument is the design of an optical flow detector which permits injection of approximately 90% of the contents of the CF for HPLC analysis. The overall size of the instrument (11 w x 16.5 h x 23.5 d in.) is smaller than commercially available instruments for protein sequencing and represents the first time an instrument has been constructed specifically for C-terminal sequence analysis. The utility of this instrument is demonstrated with the C-terminal sequence analysis of protein samples noncovalently applied to Zitex strips and with a peptide covalently attached to carboxylic acid-modified polyethylene film. PMID- 8214579 TI - Determination, purification, and characterization of alpha-NADH. AB - alpha-NADH can be determined in the presence of high concentrations of beta-NADH using anion exchange HPLC combined with oxidation of beta-NADH by lactate dehydrogenase. The method is suited for the detection of a large number of impurities. Residual absorption is a poor measure of alpha-NADH. By combination of preparative anion exchange chromatography and reversed-phase HPLC, alpha-NADH can be prepared with 95-98% purity starting from beta-NADH. Commercially available preparations contain only 80-90% alpha-NADH. The anomerization kinetics of alpha- and beta-NADH has been investigated at pH 7.0 and 7.3 taking into account the irreversible conversion reactions of alpha- and beta-NADH. The H+ ion activity related anomerization rate constants kappa 1 (alpha to beta) and kappa 2 (beta to alpha) have been found to be 170 and 29 M-1 s-1, respectively, at pH 7.0 and 192 and 36 M-1 s-1, respectively, at pH 7.3. The equilibrium constants kappa 1 /kappa 2 are 5.8 and 5.3 at pH 7.0 and pH 7.3, respectively. Absorption and fluorescence properties of alpha-NADH preparations have been determined newly. At 25 degrees C, maximum absorption was found at 260.1 and 346.6 nm, whereas at 37 degrees C the wavelengths were 260.1 and 345.3 nm. Maximum fluorescence excitation was found at 348 nm, and maximum emission was at 453 nm. PMID- 8214580 TI - A concentrating two-phase partitioning: its application to isolation of plasma membrane from maize roots. AB - An improved two-phase partitioning technique, widely applicable to the purification of biological materials, is developed. With this technique, the two phase system is obtained by mixing only two kinds of single-polymer solutions in appropriate proportions. One of the more distinctive features of this improvement is that the volume ratio between the top and the bottom phase can be changed freely without affecting the equilibrium state of the two-phase partition; this allows concurrent concentration of the objective material of purification with its partition. This technique was adapted from the conventional method of purifying maize root plasma membrane vesicles. By comparison, it was found that the improved method was simple to use, was efficient, and consumed less time and polymer material. PMID- 8214581 TI - Enzymatic amplification of a flow-injected thermometric enzyme-linked immunoassay for human insulin. AB - A flow-injected thermometric enzyme linked immunoassay for human insulin which employs the lactate dehydrogenase/lactate oxidase (LDH/LOD) substrate recycling system for signal amplification is described. The system is composed of two columns, an immunosorbent column containing immobilized anti-insulin antibodies for sensing and a recycling column containing immobilized LDH/LOD/Catalase for detection. The effect of flow rates, conjugate concentrations, and chromatographic support material upon the sensitivity of the assay are investigated. The assay has a detection limit of 0.025 microgram/ml and a linear range from 0.05 to 2 micrograms/ml. This corresponds to a 10-fold increase in sensitivity over the unamplified system. A recombinant human insulin-proinsulin conjugate was also tested. The results show that enzymatic amplification can be employed to increase the sensitivity and reproducibility of flow injection assay based biosensors. The implications of these results upon on-line analysis are discussed. PMID- 8214582 TI - A modified alkaline lysis method for the preparation of highly purified plasmid DNA from Escherichia coli. AB - We have developed a very efficient and rapid method for the preparation on a small or large scale of highly purified plasmid DNA from Escherichia coli. The procedure consists of five steps: (1) cell lysis by NaOH-SDS, (2) precipitation of cell lysate with 2 M potassium acetate-1 M acetic acid, (3) precipitation of the resulting supernatant with isopropanol, (4) treatment of the precipitate with RNase, and (5) a second isopropanol precipitation. The new procedure yields a plasmid DNA that is more than 90% in the supercoiled form and virtually free from proteins, RNA, and chromosomal DNA. We have thoroughly tested the method in the preparation of several thousand samples of different plasmids from various E. coli strains. We found that it consistently produced samples of plasmid DNA suitable for all routine uses such as restriction analysis, sequencing, and preparation of DNA probes for cloning and hybridization experiments. Moreover, plasmids purified by this procedure could fully replace plasmids purified on CsCl gradients for more demanding tasks such as the in vitro synthesis of RNA probes by phage RNA polymerases, the generation of deletion mutants with exonuclease III, and the transfection of mammalian cells by the calcium phosphate coprecipitation method, as tested on human fibroblasts and on CV-1 cells. PMID- 8214583 TI - Synthesis of PCR-derived, single-stranded DNA probes suitable for in situ hybridization. AB - We report the novel synthesis of polymerase chain reaction (PCR)-derived single stranded DNA (ssDNA) probes and their subsequent application in in situ hybridizations. Serial transverse sections of an 11.5-day postcoitum mouse embryo were hybridized to a 33P-ssDNA, 33P-RNA, or 35S-RNA probe corresponding to the same 181-bp sequence in the myogenin cDNA. Signal obtained using 33P-ssDNA was more intense than that using 33P-RNA probe, while signal/noise ratios obtained with both 33P-probes were far superior to those obtained with 35S-probe. Digoxigenin-labeled chicken growth hormone (GH) ssDNA gave slightly more intense signal than did digoxigenin-labeled chicken GH RNA when hybridized to chicken pituitary sections. 32P-ssDNA probes were found to be suitable for Northern blot hybridization. Advantages of using ssDNA probes for in situ hybridization include: (1) The ssDNA technique is rapid and simple. There was no need to clone a DNA template into a special RNA vector or order special T7-containing PCR primers. ssDNA probes can be synthesized in less than 1 day using any primers which currently exist in a laboratory (optimal probe length for in situ hybridization is between 50 and 200 bp). (2) In three separate in situ experiments, ssDNA probes yielded more intense signal than RNA probes. (3) ssDNA probes are potentially more stable than RNA probes. (4) Since the RNAse rinse is eliminated, posthybridization rinses are shortened when hybridizing with ssDNA probes. The ssDNA probes produced by this protocol can be labeled with a variety of different isotopes (both radioactive and nonradioactive), and are excellent probes for use in in situ hybridizations. PMID- 8214584 TI - Use of random primer extension for concurrent amplification and nonradioactive labeling of nucleic acids. AB - A method for efficient nonradioactive labeling of DNA with biotin using random primer extension has been developed. Under the conditions described, a significant amount of DNA synthesis occurs during incorporation of the nonradioactive label, resulting in amplification of the original template DNA. The effect of primer size, substrate concentration, enzyme concentration, and ratio of biotinylated nucleotide to normal nucleotide on the amount of DNA synthesis was determined. Amplifications of 10- to > 300-fold were attained, depending on the starting template concentration. Template may be varied from 1 to 500 ng per reaction. The size of the resulting biotinylated probes is 100-1000 nucleotides with a significant proportion in the 100-300 nucleotide range. The biotinylated probes were used to detect single-copy genes on Southern blot hybridizations and to identify specific loci in metaphase chromosome spreads by in situ hybridization followed by fluorescent detection with streptavidin fluorescein isothiocyanate. Random primer amplification and labeling provides a convenient method for preparation of biotinylated probes from small amounts of template DNA. PMID- 8214585 TI - Analysis of native collagen monomers and oligomers by size-exclusion high performance liquid chromatography and its application. AB - Collagen extracted from tissues by pepsin digestion is a mixture of monomeric and oligomeric molecules. The oligomers are held together by covalent crosslinks between molecules. A simple size-exclusion high-performance liquid chromatography (HPLC) method for separation of collagen monomers and oligomers using a Bio-Gel TSK 60XL column has been developed for type I collagen from calf skin. Factors influencing the resolution include flow rate, the protein concentration of the sample, and the injection volume. To overcome electrostatic interactions between the protein and the column packing, addition of sodium chloride to the mobile phase was required to recover protein from the HPLC column when using 5 mM acetic acid as the mobile phase. Optimum recovery and oligomer content were obtained at 0.25 M NaCl. Component peaks eluting from the column were identified as monomers and oligomers by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Application of the method showed that increasing the oligomer content of collagen preparations accelerated fibrillogenesis in vitro and decreased the ultimate fibril size produced. Also during fibrillogenesis, collagen oligomers were preferentially incorporated into fibrils, leaving only monomeric collagen in the soluble supernatant fraction. The assay was also shown to be useful for measurement of conversion of monomers to oligomers during accelerated aging of collagen fibrils at 30 degrees C in vitro. PMID- 8214587 TI - An improvement in the pyruvate dehydrogenase complex assay: a high-yield method for purifying arylamine acetyltransferase. AB - A new method for purifying arylamine acetyltransferase (AAT) has been devised using polyethylene glycol fractionation and hydroxylapatite chromatography. The new procedure gives a final yield of approximately 70% based on activity in crude homogenates and can be performed in a single day. This represents a threefold higher yield than previous methods. The procedure may be used to purify AAT from pigeon, chicken, and duck livers with equivalent yield of the final enzyme. However, the preparation from pigeon liver is preferred because of the sevenfold higher activity in this tissue. Nevertheless, if fresh pigeon livers cannot be acquired, calculations reveal that the preparation from chicken liver is comparable to that from pigeon liver acetone powder with respect to total activity obtained per gram wet weight starting material. One can also calculate that the chicken liver preparation is approximately 40 times cheaper than that from pigeon liver acetone powder, making the preparation of AAT from fresh chicken livers a good alternative when pigeon livers are not available. PMID- 8214586 TI - Reducing the heterogeneity of chemically conjugated targeted toxins: homogeneous basic FGF-saporin. AB - Basic fibroblast growth factor-saporin (FGF-SAP) is an extremely potent cytotoxic agent for cells bearing the FGF receptor. For its synthesis, the two free cysteines on the surface of basic FGF are available for linking by disulfide bridge to SAP which has been derivatized with a reactive sulfhydryl. Because of the heterogeneous nature of the synthesis, the resulting conjugate is heterogeneous as judged by gel electrophoresis. We have removed by site-directed mutagenesis one of the reactive cysteines of basic FGF and have purified monoderivatized SAP to use as the reactants. The resulting chemical conjugate shows a single band containing only 1 mol of basic FGF and 1 mol of SAP per molecule. This homogeneous conjugate is a potent cytocidal agent to cells bearing the FGF receptor. PMID- 8214588 TI - Determination of rate and equilibrium binding constants for macromolecular interactions using surface plasmon resonance: use of nonlinear least squares analysis methods. AB - Surface plasmon resonance (SPR) is a label-free, real time, optical detection method which has recently been commercialized as the BIAcore (Pharmacia). The technique relies on the immobilization of one of the interactants, the ligand, onto a dextran-coated gold surface. The second interactant, the ligate, is then injected across the surface and the interaction of the soluble ligate with the immobilized ligand is observed continuously and directly. The process of dissociation of bound ligate may also be observed directly after the sample plug has traversed the layer. Thus, the data generated contain information on the kinetic rate and equilibrium binding constants for the interaction under investigation. Historically, data from this instrument have been analyzed in terms of linear transformations of the primary data and requires that data from several ligate concentrations be analyzed to determine a single value for the association and dissociation rate constants. Here we discuss the analysis of untransformed BIAcore data by nonlinear least squares methods. The primary data are analyzed according to the integrated rate equations which describe the kinetics of the interaction of soluble ligate with immobilized ligand and the dissociation of the formed complex from the surface, respectively. Such analyses allow the direct determination of the association and dissociation rate constants for each binding experiment and, further, allow the analysis of data over a wider concentration range with lower associated errors compared to previously described methods. Through the use of modeling these interactions, we also demonstrate the limitations in determining the dissociation rate constant from the association phase of the interaction, thereby requiring that the dissociation process be analyzed. Indeed, the dissociation phase should be analyzed first to yield a relatively precise and unambiguous value of the dissociation rate constant, kd, which can then be used to constrain the analysis of the association phase to yield a better estimate of the association rate constant, k(a). We further demonstrate that, at least for the interaction investigated, the apparent rate and equilibrium binding constants determined using SPR are concentration independent and can be determined with good reproducibility. PMID- 8214589 TI - Separation and quantitation of monoclonal antibody aggregates by asymmetrical flow field-flow fractionation and comparison to gel permeation chromatography. AB - During the downstream processing of monoclonal antibodies (Mab) the formation of dimers and/or oligomers may occur. Today, the most common technique for determination of aggregate content is gel permeation chromatography (GPC) but it has limited resolution and separation speed. Oligomers are particularly difficult to resolve. Asymmetrical flow field-flow fractionation (FFF) is a new analytical method for the separation of Mab aggregates. The monomer and dimer peaks were well resolved and three additional peaks, thought to be trimers, tetramers, and pentamers were partially resolved. The total time for a separation can be kept as short as 6 min. The GPC separation takes about 15 min with less resolution. A study of the reproducibility for the two techniques revealed that the precision was slightly better for GPC. Investigation of the dependence of sample concentration showed that the load limit for FFF was about 4 micrograms of Mab. The GPC technique requires prefiltered samples in order to avoid clogging of the column. For FFF it is possible to inject samples containing precipitated material without any pretreatment. The flow conditions can be adjusted so that the precipitated material elutes with the front, well separated from the monomer peak. PMID- 8214590 TI - Assay of the acetyl-CoA probe acetyl-sulfamethoxazole and of sulfamethoxazole by gas chromatography-mass spectrometry. AB - We present gas chromatographic-mass spectrometric assays for (i) the concentration of sulfamethoxazole and (ii) the concentration and molar percentage enrichment of acetyl-sulfamethoxazole in biological fluids. The compounds are extracted with ethyl acetate, derivatized with either diazomethane or pentafluorobenzyl bromide, and analyzed by gas chromatography-mass spectrometry. Quantitation is achieved using internal standards, [2H4]sulfamethoxazole and acetyl-[2H4]sulfamethoxazole. Limits of detection are 200 nmol for the methyl derivatives and 2 nmol for the pentafluorobenzyl derivatives. The high sensitivity of the assay with the pentafluorobenzyl derivatives allows measuring in plasma and urine (i) the pharmacokinetics of sulfamethoxazole and acetyl sulfamethoxazole and (ii) the stable isotope enrichment of the acetyl moiety of acetyl-sulfamethoxazole. The latter is used as a probe for the noninvasive chemical biopsy of liver extramitochondrial acetyl-CoA. PMID- 8214591 TI - A method for the determination of UDP-glucuronosyltransferase activity toward arylcarboxylic acids. AB - A fast and reliable method for the assay of UDP-glucuronosyltransferase (UGT) activity toward aglycones containing a carboxylic acid function is described. The procedure involves incubation with UDP-[U-14C]-glucuronic acid, the common substrate for the reaction, solid-phase separation of the radiolabeled acylglucuronides and unreacted cofactor, and quantification by liquid scintillation counting. The technique was validated for each of the seven substrates tested by reversed-phase HPLC, and was then applied successfully to the determination of optimal conditions for the activation of the carboxylic acid UGT, and the estimation of kinetic constants for the glucuronidation of clofibric acid, 2-naphthylacetic acid, naproxen, and 4,4,4-triphenylbutanoic acid in rat liver microsomes. From the results obtained, we believe that this is an assay which, with only minor modification, could be applied to a wide range of carboxylic acid substrates for which, until now, specific and sensitive assays have been largely unavailable. PMID- 8214592 TI - A strategy for the amplification, purification, and selection of M13 templates for large-scale DNA sequencing. AB - A strategy addressing various aspects of generating and processing DNA sequencing templates is described. The strategy is designed for large-scale DNA sequencing projects and involves procedures for the amplification, purification, and selection of M13 DNA templates. The amplification is based on growth in liquid culture, the purification is based on a novel thermoextraction method which replaces phenol extraction and ethanol precipitation, and the template selection is based on hybridization of gridded template arrays on membranes with chemiluminescent probes. All steps are currently carried out manually but the use of standardized formats (96-well format) throughout the entire strategy provides for possible transition to partial or full automation in the future. The strategy has been developed and tested within the ongoing project of sequencing the class II region of the human major histocompatibility complex but it should be equally applicable to any large-scale DNA sequencing project. PMID- 8214593 TI - Assay of succinate dehydrogenase activity by a colorimetric-continuous method using iodonitrotetrazolium chloride as electron acceptor. AB - A spectrophotometric assay method for determining succinate dehydrogenase activity is described in which iodonitrotetrazolium chloride is used as a final electron acceptor. The enzyme activity is determined by measuring the formation of formazan due to the tetrazolium salt reduction. The assay is continuous, rapid, simple, and sensitive, and may be used in the determination of enzyme activity either in tissue homogenates or as a marker of the mitochondrial fraction in cell fractionation procedures. PMID- 8214594 TI - Quantification of free carnitine, individual short- and medium-chain acylcarnitines, and total carnitine in plasma by high-performance liquid chromatography. AB - This paper describes a method for the quantitative determination of free carnitine, acetylcarnitine, propionylcarnitine, hexanoylcarnitine, octanoylcarnitine, and total carnitine in plasma. Carnitine and acylcarnitines were extracted from 100 microliters of plasma with acetonitrile/methanol and isolated using 0.5-ml columns of silica gel. Samples were then derivatized with 4'-bromophenacyl trifluoromethanesulfonate and quantified by high-performance liquid chromatography with detection at 260 nm. Carnitine and acylcarnitines were quantified in normal human plasma and the plasma of patients diagnosed with methylmalonic aciduria, propionic acidemia, and medium-chain acyl-CoA dehydrogenase deficiency. PMID- 8214595 TI - Infrared investigation on the conformation of proteins deposited on polyethylene films. AB - Aqueous protein solutions deposited and dried on thin polyethylene sheets were analyzed by Fourier transform infrared spectroscopy. This convenient sampling method produced reliable estimates of protein secondary structure on relatively small quantities of protein. The total amount of protein deposited and examined by infrared spectroscopy ranged from 200 to 80 micrograms. To estimate secondary structure, principal component regression and partial least squares (PLS) analyses were applied to the infrared spectra from 12 different deposited proteins. Principal component regression with five principal components provided the fractions of helix, beta-sheet, turn, and other or random structure present in the proteins with standard deviations of 6.3, 7.3, 7.0, and 6.3%, respectively, compared to a reference data set of X-ray structures. Similar results were achieved through PLS analysis. Factor analysis provided reliable estimates of helix and beta-sheet structure with prediction errors similar to those obtained by other infrared methods. Analysis of various types of turn structure grouped together was unsuccessful. PMID- 8214596 TI - Determination of the 13C-labeling pattern of glucose by gas chromatography-mass spectrometry. AB - We developed a gas chromatography-mass spectrometric method which allows to determine the complete 13C-labeling pattern of glucose. The method uses four derivatives of glucose (methyloxime trimethylsilyl, bisbutylboronate acetate, aldonitrile pentaacetate, and permethyl) and selective analysis of fragment ions retaining specific carbon atoms. The technique was tested by analyzing glucose from rat livers perfused with various 13C tracers. The labeling patterns agree with theoretical calculations and with literature reports where [14C]glucose was analyzed by degradation and [13C]glucose was analyzed by NMR. PMID- 8214597 TI - Hormone-inducible expression and metal affinity chromatography of recombinant proteins in Saccharomyces cerevisiae. AB - An economical method to express recombinant protein in yeast (Saccharomyces cerevisiae) was developed. We combined two principles: Ni(2+)-agarose-based affinity purification of fusion proteins and expression from a cassette regulated by steroid hormones. After induction by desoxycorticosterone, > 90% pure protein was obtained after a single round of metal affinity chromatography. Gentle lysis conditions allowed the preservation of enzymatic activity. Average yields of 10 mg protein per liter of culture were obtained at a fraction of the cost of other eukaryotic expression systems. PMID- 8214598 TI - Detection of ascorbate peroxidase activity in native gels by inhibition of the ascorbate-dependent reduction of nitroblue tetrazolium. AB - A method for the detection of ascorbate peroxidase activity in native electrophoretic gels is described. The assay is based on the ability of ascorbate peroxidase to prevent the ascorbate-dependent reduction of nitroblue tetrazolium in the presence of H2O2. The method was found to be both sensitive (detection of less than 0.01 units of ascorbate peroxidase activity) and specific for ascorbate peroxidase activity. The application of the method for the detection of ascorbate peroxidase activity in protein extracts from several plant sources was investigated by comparing staining for activities of ascorbate peroxidase, horseradish peroxidase, and ascorbate oxidase and by immunodetection of ascorbate peroxidase in these extracts. PMID- 8214599 TI - Cloning of a cDNA encoding an RNA binding protein by screening expression libraries using a northwestern strategy. AB - Successful cloning with cDNA expression libraries involves interaction of ligand molecules (probes) with expressed fusion proteins of interest. So far those ligands leading to successful results fall into three classes: (i) antibodies, (ii) protein ligands that interact with the protein of interest, and (iii) DNA sequences recognized by transcription factors. We have previously identified a 50 kDa protein (called DSEF-1) which interacts with a functionally important 14-base G-rich RNA sequence located downstream of the simian virus 40 late polyadenylation signal. By using small RNAs containing the DSEF-1 binding site as probes, a cDNA clone was isolated whose gene product interacted in a sequence specific fashion with the DSEF-1 binding site. This RNA binding protein contains three potential RNA recognition motifs. We present here a procedure to obtain cDNA clones of RNA binding proteins using recognition site probes. PMID- 8214600 TI - Variation of one unit of activity with oxidation rate of organic substrate in indirect superoxide dismutase assays. AB - Although numerous reviews and articles have been written about indirect superoxide dismutase assays, little has been reported about the variation of the amount of superoxide dismutase giving 50% inhibition (SOD50), defined as one unit of dismutase activity, with variations in assay conditions. This report indicates that there is a linear dependence of the SOD50 on the magnitude of the uninhibited rate of oxidation of the organic substance for two indirect assays, one involving epinephrine autoxidation and the other NADH oxidation. For one indirect assay involving an acceleration of the oxidation rate of an organic substrate, the amount of superoxide dismutase giving a doubling of the oxidation rate, defined as one unit of dismutase activity, also shows this linear dependence on the autoxidation rate of the organic substance. The significance of this dependence and its implications for experimenters using these assays is discussed. PMID- 8214601 TI - DNA sequencing on minigels: an alternative technique for routine analyses. PMID- 8214602 TI - A small volume infrared transmission cell for aqueous solutions. PMID- 8214604 TI - Quantitation of reactions by reference to maximal peak values rather than to baseline values. PMID- 8214603 TI - Cross-linking of [35S]ATP gamma S to cell surface ATP binding sites. PMID- 8214605 TI - Effect of solvent type on the determination of total iodine in milk powder and human serum by inductively coupled plasma mass spectrometry. AB - A method for the determination of the total iodine content in milk powder and human serum by inductively coupled plasma mass spectrometry is described. It is shown that the oxidation state of the analyte has a strong impact on the analytical performance. If iodine is present as iodide and nitric acid is used for acidification, the observed ion signal is not stable and samples spiked with iodide yield erroneous recoveries up to 750%. Hence, as the iodine in milk powder is present almost exclusively as iodide, destruction of the sample with nitric acid is not suitable. It was found that such an excessive spike recovery does not occur if ammonia solution instead of nitric acid is used as the diluent. The proposed sample preparation was tested by analysing three reference milk powders, namely Certified Reference Materials 150 and 151 Spiked Skim Milk Powder (from the Community Bureau of Reference) and Standard Reference Material 1549 Non-Fat Milk Powder (from the National Institute of Standards and Technology). Good agreement with the certified values was obtained, indicating that no significant errors are introduced. For human serum, samples treated with nitric acid or with ammonia solution gave results that were not significantly different from each other. Results are given for both a 'second-generation' biological reference material, Freeze-Dried Human Serum (University of Ghent), and for sera from healthy individuals. PMID- 8214606 TI - Atomic absorption spectrometric detection of biotin-cymantrene as a metallo tracer for the avidin-biotin system. AB - Biotin-cyclopentadienylmanganese tricarbonyl (biotin-cymantrene; biotin-Cy) is proposed as a universal metallo-tracer for immunoassays. Associated with the possibility of detecting this type of label (organometallic moieties) along with different analytical procedures, this reagent appears to be a universal system with the advantages of being inexpensive, stable and directly detected (no substrate is required). The optimum conditions for detecting the organometallic label biotin-Cy with a Zeeman atomic absorption spectrometer and the affinity of biotin-Cy for the streptavidin ligand immobilized on the walls of microtitre plates, wells or tubes are described. The results obtained demonstrate the possibility of assaying a wide range of clinical parameters because the detection limit of biotin-Cy is about 1 pg per assay. Based on the competition between immobilized bovine serum albumin adsorbed on the wall and free bovine serum albumin for specific polyclonal antibodies, the streptavidin-metallo-biotin system was tested on a competitive immunoassay model and a satisfactory calibration graph was obtained. PMID- 8214607 TI - Electrocatalytic reduction of hydrogen peroxide at a stationary pyrolytic graphite electrode surface in the presence of cytochrome c peroxidase: a description based on a microelectrode array model for adsorbed enzyme molecules. AB - Electrochemical reduction of H2O2 at pyrolytic graphite disc electrodes of radius 2.5 mm occurs at readily accessible potentials (600 mV versus the standard hydrogen electrode) in the presence of yeast cytochrome c peroxidase. Introduction of the enzyme into the electrolyte solution initiates large changes in the ellipsometric angles measured for the electrode-solution interface, consistent with time-dependent enzyme adsorption. This process may be correlated with changes in electrochemical activity. Over the same time course, linear-sweep voltammograms are characterized by a transition from a sigmoidal to a peak-type waveform. It is proposed that the time-dependent behaviour may be rationalized by use of a microscopic model for substrate mass transport, in which the two electron reduction of peroxide occurs at electrocatalytic sites consisting of adsorbed enzyme molecules. A voltammetric theory based on treating the adsorbed redox enzymes as an expanding array of microelectrodes is in excellent agreement with experiment. PMID- 8214608 TI - Layer V pyramidal cells in the adult human cingulate cortex. A quantitative Golgi study. AB - The anterior and posterior parts of the human cingulate cortex differ in their absolute number of neurons per unit volume, with fewer neurons in the anterior part. To test the hypothesis that lower absolute number and packing density of neurons in the anterior cingulate cortex are associated with an increased complexity in the neuropil compartment, dendritic arborizations of layer V neurons in both cingulate parts were analyzed in a Golgi study. Results show that these neurons in the anterior cingulate cortex have more primary and secondary basal dendrites than those in the posterior cingulate cortex. This establishes an association of a higher complexity of the dendritic arborization in the anterior cingulate cortex with a lower cell number per unit volume and larger neuropil compartment. The significant lower degree of dendritic arborization in the posterior cingulate cortex is accompanied by a higher cell packing density. These structural differences are associated with functional differences between the two parts of the human cingulate cortex. PMID- 8214609 TI - Characteristics of cultured subepithelial fibroblasts of rat duodenal villi. AB - Subepithelial fibroblasts, which form a cellular network beneath the epithelium of rat intestinal villi, were cultured, and their morphological characteristics were examined. These fibroblasts, which migrated from epithelium-free villi (isolated primarily from duodenum) were flat in shape after 2 days of culture. The flat cells, each resembling a maple leaf, were rich in bundles of microfilaments, and were connected to each other by a few small gap junctions, ascertained from freeze-fracture and dye-coupling experiments. The morphology of the flat cells changed to a stellate form, with thin processes, within 30 min-1 h of reducing the serum concentration and adding dibutyryl cyclic AMP (dBcAMP), forskolin, and cholera toxin. Upon removal of dBcAMP and addition of fetal calf serum, the cells rapidly reassumed their original flat shape. Cells that were stellate in the presence of dBcAMP reassumed a flat morphology within several minutes after the addition of endothelin-1. This conversion occurred with or without extracellular Ca2+. An accompanying rearrangement of the cytoskeleton during shape conversion was observed by fluorescence immunohistochemistry. PMID- 8214610 TI - Lectin-binding sites during postnatal differentiation of normal and cystic rabbit renal corpuscles. AB - Fluorochrome-labeled lectins were used to study the expression of glycoconjugates during the postnatal differentiation of normal and cystic rabbit renal corpuscles. Glomerular cysts (GC) are induced in the rabbit by a single injection of corticoids. The Bowman's capsule of these cysts is exclusively formed of podocytes (parietal podocytes). During normal development, the cell coat of the podocytes is intensely positive for wheat germ agglutinin (WGA) and Maclura pomifera agglutinin (MPA). This reaction decreases considerably during maturation, in parallel with an increase in the number of binding sites masked by terminal sialylation. Throughout the stages studied, the podocyte coat is peanut agglutinin (PNA)-negative, but it becomes intensely positive after neuraminidase treatment. Visceral and parietal podocytes in the glomerular cysts show the same pattern of glycosylation as the normal podocytes. In contrast, normal parietal cells only transiently expressed a weak reactivity to WGA and MPA during the first stages of differentiation, and did not express cryptic binding sites at any stage. The glomerular basement membrane (GBM) is positive to WGA, to succinylated WGA, and to MPA, in all the stages studied. Maturation of the GBM is characterized by expression of cryptic MPA-binding sites, and by a considerable increase in the number of cryptic PNA-binding sites. The basement membrane of the parietal layer of the cystic Bowman's capsule shows the same pattern of glycosylation, despite the fact that this epithelial layer is solely formed of podocytes and lacks endothelial cells. In contrast, the normal parietal basement membrane does not express PNA or MPA cryptic sites at any stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214612 TI - Chick gonadogenesis following early surgical bursectomy. I. Histological, morphometric and histochemical data on the embryonic left ovary. AB - Left ovaries of bursectomized chick embryos were examined on the 17th day of incubation in comparison to normal and sham-operated controls, by histological and histochemical observations. The results show that in bursectomized embryos the cortex appears irregularly developed, with a significant decrease in the mean thickness and in the percentage of the secondary sex cords in the total cortical area. Furthermore, the germinal epithelium appears thicker and the subcortical medulla and the tunica albuginea more compact. The greater activity of the enzyme delta 5-3 beta-hydroxysteroid dehydrogenase (delta (5)3 beta HSD) found in ovaries of bursectomized embryos (histochemical method) could be related to an endocrine dismetabolism affecting the cortical development. On the basis of these results and those of other authors, some hypotheses are advanced. In particular, an action of the bursal factor on GTH receptors could be the factor responsible of the enhanced steroidogenic activity altering the hormonal environment. PMID- 8214611 TI - Co-localization of serotonin and GABA in neurons of the Xenopus laevis retina. AB - Serotonin-synthesizing neurons in the retina of Xenopus laevis have been identified using anti-phenylalanine hydroxylase (PH) antibody which recognizes tryptophan 5-hydroxylase, the rate-limiting enzyme for serotonin synthesis. Double-labelling experiments, using anti-PH antibody and anti-serotonin antibody/5,7-dihydroxytryptamine (5,7-DHT) uptake, have shown that some serotonin like immunoreactive/5,7-DHT-labelled neurons exhibit PH-like immunoreactivity (PH LI) (serotonin-synthesizing neurons), but the others do not (serotonin accumulating neurons). In the present study, triple-labelling experiments were performed using 5,7-DHT uptake and antibodies raised against GABA and PH, to determine the possible co-localization of y-aminobutyric acid (GABA) in serotonin synthesizing and/or -accumulating neurons in the Xenopus retina. All 5,7-DHT labelled bipolar cells lacked PH-LI; all of them were immunoreactive to GABA. In contrast, all 5,7-DHT-labelled large amacrine cells exhibited PH-LI, but none of them expressed GABA-LI. Small amacrine cells labelled with 5,7-DHT but not PH-LI exhibited GABA-LI, whilst the small amacrine cells with PH-LI lacked GABA-LI. These observations indicate that GABA is co-localized in serotonin-accumulating amacrine and bipolar cells, whereas serotonin-synthesizing large and small amacrine cells do not contain GABA-LI. PMID- 8214613 TI - Late developmental changes of the innervation densities of the myelinated fibres and the outer hair cell efferent fibres in the rat cochlea. AB - The baso-apical distributions of the myelinated nerve fibres (representative for the inner hair cell afferent fibres) and the outer hair cell efferent fibres were studied during postnatal development of the rat cochlea. The myelinated fibres were counted in the primary osseos spiral lamina from semi-thin sections. The outer hair cell efferent fibres were counted in the tunnel of Corti by means of ultra-thin sections. The developmental changes of the myelinated fibres were investigated between 8 and 60 days after birth (DAB); those of the outer hair cell efferent fibres between 20 and 30 DAB. Between 12 DAB (onset of hearing) and 20 DAB the baso-apical distribution of the myelinated fibres does not change. Striking maturational changes occur later after the onset of hearing, between 20 and 30 DAB. The innervation density of the myelinated fibres increases in the lower middle region of the cochlea. In this region a maximum of innervation density appears. The efferent fibres to the outer hair cells show at 20 DAB a maximum of innervation density in the middle of the cochlea but between 20 and 30 DAB, the fibre density decreases in this region. During the same period the maximum of innervation density shifts towards the base. The change in the innervation densities of the myelinated fibres and the outer hair cell efferent fibres occurs late in development, after the onset of hearing, and after the organ of Corti shows an adult-like appearance. PMID- 8214614 TI - The involvement of TGF beta 1 in early avian development: gastrulation and chondrogenesis. AB - We examined the effects of transforming growth factor-beta 1 (TGF beta 1) and a neutralizing monoclonal antibody on two phases of early chick embryo development: gastrulation and chondrogenesis. We carried out experiments in vivo and in vitro on mesoderm cells from the gastrulating embryo at day 1, and on sclerotome cells from day 3 embryos, having previously shown that this factor is present among these cells at these stages of development. Addition of the antibody to cultures of these cells produced a dose-dependent decrease in cell out-growth and spreading and concomitantly reduced fibronectin deposition. In vivo studies of the effects of TGF beta 1 on mesoderm during gastrulation were carried out by grafting beads carrying this agent into gastrulating embryos. We used beads of ion-exchange resin as well as hydrolysed polyacrylamide, and found that the grafts produced an accumulation of mesoderm cells around the implant and, at later stages, the formation of enlarged somites. There was no effect on embryonic axis formation. Studies of bromodeoxyuridine (BrdU) incorporation indicated that the mesoderm accumulation was due, at least in part, to an increase in cell proliferation. However, examination of the effect of TGF beta 1 on BrdU incorporation by mesoderm during gastrulation and sclerotome cells in vitro indicated in inhibition of cell proliferation, an inconsistency explained in terms of the variation between the in vivo and in vitro conditions. We conclude that TGF beta 1 is both appropriately located, and is able, to influence cell proliferation among the mesodermal cell populations during early development, and that this effect contributes to the overall control of mesodermal morphogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214615 TI - Ontogeny of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta HSD) in rat testis as studied by immunocytochemistry. AB - The enzymatic complex 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) is a step essential in the biosynthesis of all biologically active steroids, including androgens. In order to obtain information about the expression of 3 beta-HSD during testis development, we have localized this enzyme by light microscope immunocytochemistry during fetal and postnatal periods of development in the rat. In fetal testis, the enzyme was first detected in a few Leydig cells on the 17th day of gestation. The number of labeled cells and intensity of labeling increased with fetal development. From days 19 to 21 of gestation, strongly immunoreactive Leydig cells were arranged in clusters between seminiferous tubules. During the first days following birth, the number and size of positive cells rapidly decreased so that on postnatal days 5 and 10 only small, poorly stained cells could be seen. Fifteen days after birth, positive Leydig cells appeared more numerous and localized in peri- and intertubular spaces. At the onset of puberty, the intensity of labeling markedly increased. After puberty, and during adulthood, both strongly and weakly stained Leydig cells were mainly localized in intertubular spaces. Since the fluctuations in 3 beta-HSD content revealed in the present study by immunocytochemistry appear similar to those already observed for androgen secretion, such data suggest that regulation of 3 beta-HSD by trophic hormones might play an important role in regulating testicular androgen production during fetal as well as postnatal development. PMID- 8214616 TI - The ciliary ganglion of the cat: a light and electron microscopic study. AB - The ciliary ganglia of eight healthy adult cats were studied by light and electron microscopy. The ganglion, measuring about 2 mm in length, was consistently found to be attached to the branch from the oculomotor nerve supplying the inferior oblique muscle. The number of neurons varied from 2773 to 3794 after applying Abercrombie's correction. The mean of average somal diameter of the neurons was 36.5 microns (SD = 5.0 microns) and the mean of somal cross sectional area was 904.2 microns 2 (SD = 262.8 microns 2). The mean of average nuclear diameter was 13.9 microns (SD = 1.8 microns) and the mean of nuclear cross-sectional area was 142.2 microns 2 (SD = 37.1 microns 2). The mean of the aspect ratios of the soma and nucleus were 1.2 (SD = 0.1) and 1.1 (SD = 0.1) respectively. The frequency distributions of these parameters were all unimodal. Under the light microscope, the Nissl granules in the neurons were prominent and were distributed peripherally, perinuclearly or randomly in the cytoplasm. Under the electron microscope, the rough endoplasmic reticulum showed a similar pattern of distribution in the cytoplasm. In some neurons, glycogen-like granules were present; these were either distributed randomly throughout the cell, or aligned in single rows in relation to subsurface cisterns and between the cisterns of smooth and rough endoplasmic reticulum. Most of the dendrites were short protrusions from the cell body; some contained glycogen-like granules. Occasionally, the dendritic protrusions were electron-dense. All the synapses encountered were axodendritic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214617 TI - Ultrastructural localization of laminin subunits during the onset of mesoderm formation in the mouse embryo. AB - Using ultrastructural immunogold histochemistry on LR-Gold-embedded 6- and 7-day old mouse embryos we investigated the appearance of the A- and B1-chains of the laminin molecule during mesoderm formation. With the help of antibodies against the A-chain and the E4 fragment of the B1-chain of the laminin molecule we were able to detect the subunits in vivo. Staining for the E4 fragment of the short arm of the laminin molecule from day 6 was negative. In contrast, strong staining for the A-chain of laminin was observed. Our results show, that the A-chain of laminin appears before the B1-chain in the 6-day-old mouse embryo before a basement membrane is seen between the ectodermal and entodermal cell layers. Furthermore, the staining pattern indicates, that the laminin molecule changes its orientation in the basement membrane of the ectoderm during mesoderm formation. On day 7 staining for the A-chain of laminin and for the E4 fragment was seen in a random distribution throughout the entire basement membrane, whereas in areas were the onset of mesoderm formation was taking place, the E4 fragment was restricted to the edge of the disintegrating basement membrane. PMID- 8214618 TI - Ultrastructural localization of calcium in the chick yolk sac membrane endodermal cells as revealed by cytochemistry and X-ray microanalysis. AB - The yolk sac membrane (YSM) of the chick embryo transports calcium from the yolk into the embryonic circulation during the first half of development, but the intracellular pathway of calcium transport is poorly understood. In the present study, the ultrastructural localization of calcium was investigated in cells of the YSM of 9-day chick embryos. X-ray microanalysis as well as cytochemical techniques performed on yolk sac membrane cells treated with potassium oxalate, potassium ferricyanide and potassium antimonate demonstrated accumulation of calcium in yolk granules, digested yolk products, electron-dense bodies (EDBs; 100-400 nm diameter) and electron-dense granules (EDGs; 30-50 nm diameter). When strontium ions were injected into the yolk, they were incorporated into the endodermal cells and sequestered specifically in EDGs. From these results, we propose that calcium enters the endodermal cells by endocytosis of calcium containing yolk granules, as well as through calcium channels in the apical cell membrane. In the cytoplasm, digested yolk products, EDBs, and EDGs act as sites of sequestration and accumulation of calcium. Extrusion of intracellular calcium into the extracellular space and embryonic circulation is accomplished by exocytosis of calcium-containing material and via an ion pump in the basal cell membrane. PMID- 8214619 TI - Axis development in avian embryos: the ability of Hensen's node to self differentiate, as analyzed with heterochronic grafting experiments. AB - A series of experiments consisting of transplantation of Hensen's nodes has been conducted to examine axis development in avian embryos. In the first group of experiments, Hensen's nodes from quail embryos were transplanted homotopically and either isochronically or heterochronically to chick embryos, and the structures derived form the grafted nodes were assessed. The grafted Hensen's nodes typically self-differentiated structures appropriate for their stages, and the host embryos developed normally; the structures formed from grafted tissue usually merged caudally with the comparable host structures. Thus, even when the stages of the donor and host tissues were significantly mismatched (e.g., stage 3 donors and stage 9 hosts or vice versa), the graft was unable to repattern the host's neuraxis, and the host was unable to respecify the types of structures derived from the graft. In the second group of experiments, Hensen's nodes from quail embryos were transplanted to sites located just lateral to Hensen's nodes of host chick embryos, thereby providing the potential for development of additional axes. A single axis always resulted in each case in which further development occurred, with the graft self-differentiating its typical stage specific structures, all of which merged caudally with comparable host structures. A final group of experiments served principally as a control and tested the ability of a part of Hensen's node, when it was transplanted to the extraembryonic germ cell crescent, to organize an ectopic embryo. In these experiments, the entire thickness and length of each Hensen's node, but only the central one-third to one-half of its width, was transplanted to host blastoderms, yet ectopic embryos, complete with induced neuraxes, were formed. Therefore, a part of Hensen's node has the ability to function fully as an organizer when placed in a conducive environment. Collectively, these results provide further documentation of the strong ability of Hensen's node to self-differentiate, and they suggest that once morphogenetic movements are under way, neuraxial structures can form, and characteristic rostrocaudal patterning of the neuraxis can occur, without sustained influence from Hensen's node. PMID- 8214620 TI - Chondroitin sulphate proteoglycan and embryonic brain enlargement in the chick. AB - Previous studies of the early development of the neural tube have shown the existence of an intraneural fluid, which causes a positive pressure inside this primordium, and seems to play a key role in the early development of the central nervous system. In the present study we investigated the composition and synthesis of this intraneural fluid. By using a sequential method, which includes fixation with glutaraldehyde plus cetylpyridinium chloride, opening the neural cavity after critical point drying and scanning electron microscopy analysis, we found a water-soluble extracellular matrix that filled up the brain vesicles of chick embryos at the earliest stages of the neural tube. An ultrastructural study of the neural epithelium during these stages revealed the existence of a secretion process in the neural cells toward the apical side, the future neural cavity. An immunocytochemical study to assess the nature of the secreted material has shown that the intraneural matrix contains chondroitin sulphate proteoglycan, which appeared homogeneously distributed throughout the neural cavity. Our findings demonstrate that the intraneural liquid is a fluid of complex composition and includes chondroitin sulphate proteoglycan as an osmotically active molecule. This suggests a morphogenetic role for the proteoglycan during early brain enlargement. The neural ectoderm is a polarized epithelium from early developmental stages and secretes the intraneural matrix. PMID- 8214621 TI - Expression of the neural cell adhesion molecule (NCAM) during second- and third molar development in the mouse. AB - Distribution of the neural cell adhesion molecule (NCAM) during the development of the mandibular second- and third-molars of the mouse was studied by indirect immunofluorescence techniques. At the initial stage, NCAM was intensely expressed by the mesenchymal cells surrounding the dental lamina, and by the cap stage NCAM expression by the mesenchymal cells became restricted to the dental follicle. After that, in addition to the follicular mesenchyme, some cells in the basal part of the dental papilla showed NCAM-immunoreactivity for a while after the hard tissue formation had started. During root formation, the follicular cells lost NCAM first from the level of the cervical root and later from the coronal part, while an additional NCAM positive area appeared deep in the dental papilla. Even after the teeth had erupted, NCAM was expressed in the tissue surrounding the apical root and in the pulp core. During the initial and bud stages, the pattern of NCAM expression in the second and third molars was different from that in the first molar, where NCAM was found only after the late bud stage; while from the cap stage onward, it changed in the same sequence as in the first molar. The different pattern of NCAM expression implies that there is a difference in developmental events between the early stages of the first and the other two molars. On the other hand, the common sequence of NCAM expression in the tooth germs later than the cap stage suggests that NCAM plays an essential role in the formation of the basic structure of the teeth and periodontal tissues. PMID- 8214622 TI - Perivascular astrocytes and endothelium in the development of the blood-brain barrier in the optic tectum of the chick embryo. AB - The role played by perivascular astrocytes in neural vessel maturation was investigated in microvessels of the chick embryo optic tectum. Three-dimensional reconstructions and quantitative analyses were made, and permeability was studied. On embryonic days 14-16, 12.5% of the microvessel wall is surrounded by astrocyte endfeet which, in most cases (82%), are located under endothelium junctions; the latter, at this stage, partly prevent the extravascular escape of the marker horseradish peroxidase. On days 18-21, the astrocyte processes form a nearly complete perivascular sheath enveloping 96% of the microvessel perimeter; the junctions of the endothelial cells are much wider and impermeable owing to extensive fusion of the endothelial plasma membranes. This investigation suggests a close relationship between the perivascular arrangement of glia and differentiation of the endothelium tight junctions and indicates that the morphofunctional maturation of the latter takes place progressively during the prenatal organogenesis of the chick central nervous system. PMID- 8214623 TI - The process of calcification during development of the rat tracheal cartilage characterized by distribution of alkaline phosphatase activity and immunolocalization of types I and II collagens and glycosaminoglycans of proteoglycans. AB - The rat tracheal cartilage was shown to calcify during development. The process of calcification was characterized in terms of distribution of alkaline phosphatase (ALP) activity and alterations to immunolocalization of types I and II collagens and glycosaminoglycans of proteoglycans during the development of the tracheal cartilage, in comparison with calcification of the epiphyseal growth plate cartilage. ALP activity was not identified in the tracheal cartilage in the course of calcification, which therefore differed from that in the growth plate. The tracheal cartilage matrix was not resorbed or invaded by type I collagen during calcification. This suggests that no osteogenesis is involved in calcification of the cartilage. Immunoreactivity for type II collagen became weaker in the central region of the tracheal cartilage during development. No net loss of proteoglycans was identified with Alcian blue staining after calcification of the tracheal cartilage. Immunoreactivity for chondroitin 4 sulphate increased in the calcified tracheal cartilage, while reactivity for chondroitin 6-sulphate was weaker in the calcified area than in the surrounding uncalcified region of the tracheal cartilage. The alteration of the extracellular matrices during development may be involved in the calcification of the rat tracheal cartilage. PMID- 8214624 TI - A pilot study on morphological compartmentalization and heterogeneity in the elasmobranch olfactory bulb. AB - The olfactory bulb of many elasmobranch fishes is morphologically subdivided into distinct units or sub-bulbs immediately adjacent to the olfactory epithelium. We investigated this morphological feature in two species of shark and one species of ray in order to understand its impact on the arrangement of the primary olfactory projections onto the bulb. Using anterograde tracing methods in vitro (biocytin) as well as in fixed tissue (DiI), we observed a direct segregated projection of the olfactory afferents onto the bulb. Application of tracers to the lateral part of the olfactory epithelium resulted in staining restricted to this region of the bulb, whereas the same tracers applied to the medial part of the epithelium resulted in staining of the medial olfactory bulb. The sub-bulbs appear to be individual anatomical units that each receive input from the olfactory lamellae. Nissl and myelin staining as well as the Golgi method show that the cytoarchitecture of the sub-bulbs is not substantially different from that of other anamniotes. However, we did note the existence of two types of mitral cell, based on the morphology of their dendritic arborization. Type L cells exhibit a loose dendritic arborization, whereas type T cells are characterized by a dense, bush-like dendritic arborization. Both types of mitral cells lack basal dendrites. PMID- 8214625 TI - Postnatal development of parvalbumin and calbindin D28K immunoreactivities in the cerebral cortex of the rat. AB - Parvalbumin and calbindin D28k immunoreactivities were examined in the neocortex of the rat during postnatal development. Parvalbumin-immunoreactive nonpyramidal neurons first appear in layer V and later in layers VI and IV, and then in II and III. Immunoreactive terminals forming baskets surrounding unlabelled somata appear about 2 days later. The first parvalbumin-immunoreactive neurons appear in the retrosplenial and cingulate cortices, and the rostral region of the primary somatosensory cortex at postnatal days 8 or 9 (P8-P9). These regions are followed by the primary visual, primary auditory and motor cortices at P11. Parvalbumin immunoreactivity appears last in the secondary areas of the sensory regions and association cortices. Adult patterns are reached at the end of the 3rd week. Calbindin D28K-immunoreactive nonpyramidal neurons are found at birth in all cortical layers excepting the molecular layer. The intensity of the immunoreaction increases during the first 8 or 11 days of postnatal life, first in the inner and later in the upper cortical layers, following, therefore, an "inside-out" gradient. Heavily-labelled calbindin D28K-immunoreactive nonpyramidal cells dramatically decrease in number from P11 to P15 due mainly to a decrease of the multipolar subtypes. This suggests that two populations of calbindin D28k-immunoreactive nonpyramidal neurons are produced in the neocortex during postnatal development: one population of neurons transitorily expresses calbindin D28k immunoreactivity; the other population is composed of neurons that are permanently calbindin D28k immunoreactive. In addition to heavily labelled nonpyramidal cells, a band of weakly labelled pyramid-like neurons progressively appears in layers II and III throughout the cerebral cortex, beginning in layer IV in the somatosensory cortex by the end of the 2st week. Adult patterns are reached at the end of the 3rd week. These results indicate that parvalbumin and calbindin D28k immunoreactivities in the cerebral neocortex follow different characteristic patterns during postnatal development. The appearance of parvalbumin immunoreactivity correlates with the appearance of the related functional activity in the different cortical regions, and, probably, with the appearance of inhibitory activity in the neocortex. On the other hand, the early appearance of calbindin D28k immunoreactivity in the neocortex may be related to the early appearance of calbindin immunoreactivity in many other brain regions, and suggests another, as yet unknown, role for this calcium-binding protein during development of the cerebral cortex. PMID- 8214626 TI - Testicular and epididymal development in the brown marsupial mouse, Antechinus stuartii (Dasyuridae, Marsupialia). AB - Reproductive tissues were collected monthly from male Antechinus stuartii during the first 5 months of post-partum development, a period corresponding to the time between birth and the initial increase in plasma androgen above non-detectable levels. The gonad appeared undifferentiated at day 3 after birth, but the basic structure of the testis (tunica albuginea, sex cords, stroma) was well established at 1 month of age. At this stage the developing sex cords contained a single layer of pre-Sertoli cells which surrounded a central core of gonocytes. Mitotic division of cells within the cords was common. Intertubular fetal Leydig cells, often observed in clumps, and perivascular and peritubular fetal Leydig cells were common and readily identified. By 2 months of age there was an obvious increase in cord diameter and the abundance of pre-Sertoli cells, while a marked reduction in the density of connective tissue cells and fetal Leydig cells was observed in the interstitium. Fetal Leydig cells appeared to persist only in close association with the developing seminiferous cords. Testicular size and the diameter and convolutions of the seminiferous cords increased substantially (two fold increase in cord diameter) by 3 months of age. Gonocytes had begun to migrate toward the basal lamina of the cords, and connective tissue cells and Leydig cells appeared in large numbers throughout the interstitium. By 4 and 5 months of age, gonocytes were commonly seen in contact with the basement membrane, and the cords remained non-patent. Leydig cell number and density increased greatly during these months. The epididymal epithelium remained undifferentiated throughout the first 5 months of development. Epithelial cells characteristically contained a large nucleus which occupied most of the cell, very little cytoplasm and few organelles. The diameter of the epididymal duct was similar throughout for the first 3 months of the study. In months 4 and 5 the diameter of the duct in caput and corpus regions increased, ahead of that of the cauda, possibly in relation to variations in androgen exposure at different regions along the developing duct. Further histological and quantitative studies on the growth and development of Leydig cells within the Dasyuridae are needed for comparison with eutherian mammals, which together with knowledge of the changing levels of fetal androgens may provide a greater understanding of the role of the different populations of Leydig cells in the differentiation of the testis and male reproductive tract.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8214627 TI - Zinc-positive afferents to the rat septum originate from distinct subpopulations of zinc-containing neurons in the hippocampal areas and layers. A combined fluoro gold tracing and histochemical study. AB - The purpose of the present study was to examine whether zinc-positive and zinc negative hippocampal neurons in rats differed with respect to their projections to the septum. By combining retrograde axonal transport of the fluorescent tracer Fluoro-Gold with histochemical demonstration of zinc selenide complexes in zinc containing neurons after intraperitoneal injection of sodium selenite, we were able to visualize the distribution of retrogradely Fluoro-Gold labeled neurons and zinc-containing neurons in the same sections. After unilateral injection of Fluoro-Gold into the rat septum a few retrogradely labeled cells were observed in layer IV of the ipsilateral medial entorhinal area, and numerous labeled cells were observed mainly in the superficial layers of the ipsilateral subicular areas and throughout the CA1 and CA3 pyramidal cell layers, as well as in the contralateral CA3 pyramidal cell layer. Zinc-containing neurons were observed in layers IV-VI of the medial entorhinal area, layers II and III of the parasubiculum, layers II, III and V of presubiculum, and in the superficial CA1 and deep CA3 pyramidal cell layers. Cells double-labeled with Fluoro-Gold and zinc selenide complexes were primarily located in distal (relative to the area dentata) parts of the superficial CA1 pyramidal cell layer and distal parts of the deep CA3 pyramidal cell layer and in layers II and III of presubiculum. Only a very few double-labeled cells were seen in the contralateral CA3. The result demonstrates that the hippocampo-septal projection of rats is a mixture of zinc positive and zinc-negative fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214628 TI - Several neuronal and axonal types form long intrinsic connections in the cat primary auditory cortical field (AI). AB - Intrinsic connections in the cat primary auditory field (AI) as revealed by injections of Phaseolus vulgaris leucoagglutinin (PHA-L) or biocytin, had an anisotropic and patchy distribution. Neurons, labelled retrogradely with PHA-L were concentrated along a dorsoventral stripe through the injection site and rostral to it; the spread of rostrally located neurons was greater after injections into regions of low rather than high characteristic frequencies. The intensity of retrograde labelling varied from weak and granular to very strong and Golgi-like. Out of 313 Golgi like retrogradely labelled neurons 79.6% were pyramidal, 17.2% multipolar, 2.6% bipolar, and 0.6% bitufted; 13.4% were putatively inhibitory, i.e. aspiny or sparsely spiny multipolar, or bitufted. Individual anterogradely labelled intrinsic axons were reconstructed for distances of 2 to 7 mm. Five main types were distinguished on the basis of the branching pattern and the location of synaptic specialisations. Type 1 axons travelled horizontally within layers II to VI and sent collaterals at regular intervals; boutons were only present in the terminal arborizations of these collaterals. Type 2 axons also travelled horizontally within layers II to VI and had rather short and thin collateral branches; boutons or spine-like protrusions occurred in most parts of the axon. Type 3 axons travelled obliquely through the cortex and formed a single terminal arborization, the only site where boutons were found. Type 4 axons travelled for some distance in layer I; they formed a heterogeneous group as to their collaterals and synaptic specializations. Type 5 axons travelled at the interface between layer VI and the white matter; boutons en passant, spine-like protrusions, and thin short branches with boutons en passant were frequent all along their trajectory. Thus, only some axonal types sustain the patchy pattern of intrinsic connectivity, whereas others are involved in a more diffuse connectivity. PMID- 8214629 TI - Neuroanatomical study of afferent projections to the supramammillary nucleus of the rat. AB - We examined the regions projecting to the supramammillary nucleus of the rat with retrograde transport of WGA-HRP and WGA, and anterograde transport of Phaseolus vulgaris leucoagglutinin. The supramammillary nucleus receives major descending afferents from the infralimbic cortex, the dorsal peduncular cortex, the nucleus of the diagonal band of Broca, the medial and lateral preoptic nuclei, bilaterally. The major ascending afferents come from the pars compacta of the nucleus centralis superior, the ventral tegmental nucleus, and the laterodorsal tegmental nucleus. The supramammillary nucleus also receives a few (but distinct) fibers from the anterior and lateral hypothalamic nuclei, the ventral premammillary nucleus, the interpeduncular nucleus, the cuneiform nucleus, the dorsal raphe nucleus, the incertus nucleus, and the C3 region including the prepositus hypoglossi nucleus. All descending fibers run through the medial forebrain bundle. Almost all ascending fibers from the pars compacta of the nucleus centralis superior and the laterodorsal tegmental nucleus run through the mammillary peduncle, and terminate throughout the supramammillary nucleus. A few fibers from the laterodorsal tegmental nucleus and the C3 region run through the fasciculus longitudinalis dorsalis and terminate in the dorsal part of the supramammillary nucleus including the supramammillary decussation. PMID- 8214630 TI - Morphometry of the vestibular organ in neonate and adult African mole-rats Cryptomys species. AB - The dimensions (length and cross-sectional area) of the semicircular canal of the inner ear in Cryptomys (a rodent with long gestation, and altricial young with slow, extended postnatal growth) did not change after birth. This is further evidence for the relative morphometric postnatal stability of semicircular structures in mammals. PMID- 8214631 TI - Immunocytochemical localization of corticotropin-releasing factor in the brain of the turtle, Mauremys caspica. AB - Brain sections of the turtle, Mauremys caspica were studied by means of an antiserum against rat corticotropin-releasing factor. Immunoreactive neurons were identified in telencephalic, diencephalic and mesencephalic areas such as the cortex, nucleus caudatus, nucleus accumbens, amygdala, subfornical organ, paraventricular nucleus, hypothalamic dorsolateral aggregation, nucleus of the paraventricular organ, infundibular nucleus, pretectal nucleus, periventricular grey, reticular formation and nucleus of the raphe. Many immunoreactive cells located near the ependyma were bipolar, having an apical dendrite that contacted the cerebrospinal fluid. Immunoreactive fibers were seen in these locations and in the lamina terminalis, lateral forebrain bundle, supraoptic nucleus, median eminence, neurohypophysis, tectum opticum, torus semicircularis and deep mesencephalic nucleus. Parvocellular bipolar immunoreactive neurons from the paraventricular and infundibular nuclei projected axons that joined the hypothalamo-hypophysial tract and reached the outer zone of median eminence, and the neural lobe of the hypophysis where immunoreactive fibers terminated close to intermediate lobe cells. From these results it can be concluded that, as in other vertebrates, corticotropin-releasing factor in the turtle may act as a releasing factor and, centrally, as a neurotransmitter or neuromodulator. PMID- 8214632 TI - Histochemical distribution of zinc in the brain of the zebra finch (Taenopygia guttata). AB - The distribution of zinc was studied in the brain of the zebra finch (Taenopygia guttata) by means of the selenium histochemical method. A specific pattern was seen, which usually correlated with the main known architectonic subdivisions. In addition, a few as yet unidentified structures were observed. In the telencephalon, the pallial components were stained with moderate to strong intensity. The only exceptions were the hyperstriatum intercalatus superior, a small medial area in the hyperstriatum accessorium and in the dorsolateral cortex, and the dorsomedial part of the hippocampal complex, which were virtually devoid of staining. Staining of the dorsal ventricular ridge components varied considerably. The archistriatum, the nucleus accumbens, the nucleus of the stria terminalis, the hyperstriatum ventrale and the lateral septum showed moderate to strong staining. The medial septum was weakly stained. The neostriatum showed a rather complex pattern of staining with unstained areas, such as the magnocellular nucleus of the anterior neostriatum, and other parts intensely stained, especially in its caudal region. Both paleostriatii primitivum and augmentatum showed a rostro-caudal gradient that was increasingly stained. We also observed an intensely stained area ventral to the fasciculus prosencephali lateralis and lateral to the tractus septomesencephalicus, a weakly to moderately stained band ventral to the lobus parolfactorius, an intensely stained zone along the lateral ventricle in the hyperstriatum ventrale, and an unstained almond shaped nucleus in the lateral hyperstriatum ventrale. In the diencephalon, the hypothalamus showed a moderate to strong, rather uniform staining, whereas the thalamus was usually weakly to moderately stained, with the exception of a few unstained nuclei. Only the lateral nucleus of the habenula was stained, and with strong intensity. Most of the mesencephalon stained rather uniformly with a moderate to strong intensity. The most intense staining was seen in the substantia grisea centralis, the substantia grisea et fibrosa periventricularis, the torus semicircularis and the nucleus intercollicularis. The tectum opticum was virtually devoid of stain except for two light bands in the stratum griseum et fibrosum superficiale. The formatio reticularis was moderately stained. All the other structures were either weakly stained or unstained. Some staining was seen in the Purkinje and the granular layers of the cerebellum, as well as around its internal nuclei. The pons and the medulla oblongata showed an overall moderate to intense staining, with the exception of a few unstained nuclei. When compared in three bird species belonging to different genera, zinc distribution shows remarkable similarities, despite species, age and methodological differences.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8214633 TI - Molecular heterogeneity of chondroitin sulphate in the early developing chick wing bud. AB - Proteoglycans are ubiquitous extracellular matrix molecules whose role in development remains poorly understood. In the developing chick limb, the nature and possible roles of a number of extracellular matrix proteins is well documented. Much less is known of the biochemical nature, and more importantly, the roles of proteoglycans. Using a panel of monoclonal antibodies (Mabs) which recognise specific epitopes on the constituent chondroitin/dermatan sulphate chains, we show that distinct sub-populations of proteoglycans are dynamically expressed within the limb ectoderm, the ectodermal basement membrane and the limb mesenchyme. In particular, prior to chondrogenesis, chondroitin-6-sulphate-rich proteoglycans containing over-sulphated domains residue predominantly within the mesenchymal extracellular matrix ECM, whilst chondroitin-4-sulphate (C-4-S) is associated with the ectodermal basement membrane and subjacent mesenchymal ECM. At stage 24, C-4-S is also localized in the prechondrogenic condensation. Concomitantly with overt chondrogenesis, the epitopes recognized by the Mabs become restricted to the chondrifying skeletal elements and the undifferentiated distal mesenchyme. The significance of these findings has yet to be elucidated. PMID- 8214634 TI - Modification of the phalangeal pattern of the digits in the chick embryo leg bud by local microinjection of RA, staurosporin and TGF beta's. AB - Many experimental studies show that in the avian chick limb the digits are specified at early stages of development by characteristic concentrations within the limb mesoderm of a still unidentified morphogen diffusing from the posterior margin of the bud, linked with a specific pattern of homeobox gene expression. In all these studies, digits are distinguished by their size, morphology and phalangeal pattern rather than by their position within the autopodium. In this work we report the induction of digits that have otherwise normal morphology but lack an interphalangeal joint. This suggests that the patterning of these joints is not necessarily linked to the control of the outgrowth of the digital rays. Missing interphalangeal joints were induced by microinjection into the third interdigital space of the leg bud of stage 28 to 31 chick embryos of retinoic Acid (RA), staurosporine and TGF beta 1 and beta 2, but not by microinjection of FGF or EGF. Our results also suggest that the pattern of insertion of the long tendons and the formation of the flexor cutaneous pad at the plantar surface of the digits are both linked to the establishment of the interphalangeal joints. PMID- 8214635 TI - Stretch induces non-uniform isomyosin expression in the quail anterior latissimus dorsi muscle. AB - Stretch-overload has been shown to elevate muscle mass in the avian anterior latissimus dorsi (ALD) by increasing both fiber size and fiber number; however, it is not known if these adaptations result in uniform regulation of myosin isoform expression along the length of the fibers in this slow tonic muscle. When a weight was added to the left wing of 20 adult quail for 30 days, ALD mass was increased by 161%. ALDs were divided into proximal, middle, and distal portions. Tissue cross-sections from each muscle portion were reacted against monoclonal antibodies for either fast (FM) or slow myosin (SM), or processed for identification of native myosin isoforms. The number of fibers expressing FM increased by 190% in the distal region after stretch; however, most of these were small fibers. Electrophoretic analyses of stretched muscles demonstrated an upregulation of SM2 in all regions of the ALD. SM1 was only down-regulated in the proximal region of the ALD. FM isoforms had greater increases in the proximal region than other regions of the overloaded ALD. These data indicate that stretch induced hypertrophy induces a non-uniform increase in fast myosin isoforms and SM1 along the length of the fibers of the ALD. PMID- 8214636 TI - Quantitative morphological changes in neurons and glia in the frontal lobe of the aging rat. AB - The quantitative morphological changes in neurons and glia during the aging process were analyzed in the different cortical layers, grouped as I, II-IV, V, and VI, of the frontal cortex of the rat. The parameters analyzed were cortical volume, neuronal density, glial density, and neuronal soma and nucleus areas. No changes with age were found in the volume of the layers, in neuronal density (with the exception of layer I), or in the area of the neuronal soma. However, older animals showed a 10 to 20% increase in glial density, depending on the layer studied. In addition, there was an age-related decrease in the area of the neuronal nucleus in layers II-IV, V, and VI. These results support the idea that the aging frontal cortex undergoes structural changes that may be involved in the morphological basis of memory and cognitive impairments characteristic of aging. PMID- 8214637 TI - Nucleus ambiguus of the rabbit: cytoarchitectural subdivision and myotopical and neurotopic representations. AB - The cytoarchitectural subdivisions of the nucleus ambiguus of the rabbit and its myotopical and neurotopical representations were investigated with HRP labeling. The nucleus was subdivided into the compact cell group (CoG), the medial and lateral scattered cell groups (SGm and SGl), and the diffuse cell group (DiG). The CoG was formed by esophageal, pharyngeal constrictor, and palatal motoneurons in the rostral half of the nucleus. The SGm and SGl were located medial and lateral to the CoG, respectively, in the rostral one-third of the nucleus. Stylopharyngeal and cricothyroid motoneurons were located in the most rostral one fifth of the SGm and the remaining four-fifths, respectively, whereas the SGl was not labeled with HRP injections into the palatal, pharyngeal, esophageal, and laryngeal muscles. The DiG was formed by recurrent laryngeal motoneurons in the caudal two-thirds of the nucleus. Neurons of origin for the glossopharyngeal nerve occupied the stylopharyngeal region, with a few of them scattered in the CoG and SGl. Neurons giving rise to axons in the superior laryngeal nerve occupied the cricothyroid region, with a few of them scattered in the pharyngeal constrictor region; whereas the pharyngeal vagal branch originated from the pharyngeal constrictor and palatal regions. Neurons of the DiG, SGl, and esophageal region contributed to the infranodosal vagus nerve; esophageal fibers of the recurrent laryngeal nerve originated from the dorsal esophageal region. Laryngeal fibers of the recurrent laryngeal nerve originated from the DiG, the caudal neurons of which had axons traversing the cranial accessory root. PMID- 8214638 TI - A scanning and transmission electron microscopic analysis of the cerebral aqueduct in the rabbit. AB - An examination of the surface of the cerebral aqueduct with the scanning electron microscope revealed that the walls of the cerebral aqueduct were so heavily ciliated that most of the ependymal surface was obscured, yet certain specialized supraependymal structures could be discerned lying on (or embedded within) this matt of cilia. These structures were determined by transmission electron microscopy and Golgi analysis to be either macrophages, supraependymal neurons, dendrites from medial periaqueductal gray neurons, or axons of unknown origin. Some axons, which were found to contain vesicles, appeared to make synaptic contacts with ependymal cells. Using the transmission electron microscope, the ependymal lining was found to consist of two different cell types: normal ependymal cells and tanycytes which have a long tapering basal process that was observed to contact blood vessels or, more rarely, seemed to terminate in relation to neuronal elements. While there have been previous reports on the structure of the third and lateral ventricles in other species, there are limited reports in the rabbit. The present report is not only the first description for the rabbit, but it is the first complete scanning and transmission electron microscopic analysis of the cerebral aqueduct in any species. PMID- 8214639 TI - Acetylcholinesterase activity is associated with efferent endings in the sensory epithelia of the utricle and semicircular canals of the rainbow trout inner ear. AB - The mechanosensory hair cells of the utricle and semicircular canals of the trout inner ear are morphologically similar to type II hair cells of the avian and mammalian vestibular end organs. These cells are innervated by two types of nerve terminals. The nonvesiculated terminals are considered to be afferent, and the vesiculated endings are presumed to be efferent. The presumptive efferent endings contain numerous clear, round vesicles and a few that are dense-cored. Histocytochemical, electron microscopic analysis has localized acetylcholinesterase activity to plasma membranes of vesiculated, presumptive efferent nerve terminals in sensory epithelia of the utricle and semicircular canals. No reaction product was observed at the receptoneural synapse or found in nonvesiculated, presumptive afferent endings. Control specimens incubated in the presence of eserine sulfate, an inhibitor of acetylcholinesterase, were devoid of reaction product. These results support the tenet that vesiculated nerve endings in the sensory epithelia of the utricle and semicircular canals of the trout are cholinergic. PMID- 8214640 TI - Ultrastructural characteristics of in vivo and in vitro fertilization in the grey short-tailed opossum, Monodelphis domestica. AB - To establish the mode of fertilization in a marsupial, a morphological investigation was made of the gametes of the South American grey short-tailed opossum. Monodelphis domestica, at the time of fertilization in vivo and in vitro. Oestrus was induced in females by the introduction of an unfamiliar male. To obtain oocytes recently fertilized in vivo, females were killed 18-24 hours after the first mating and the region of the oviduct containing eggs excised and fixed. Unfertilized mature oocytes were recovered from ovarian follicles 15-18 hours after first mating and fertilized in vitro with cauda epididymal spermatozoa in a modified MEM medium supplemented with bovine serum albumin at 37 degrees C in 5% CO2 in air. Following sperm-egg binding and fertilization, oocytes were fixed and prepared for light and electron microscopy. Spermatozoa unpaired prior to fertilization in vivo and in vitro and single spermatozoa bound to the zona surface by their plasmalemma overlying the acrosome on the dorsal face of the sperm head. The acrosome reaction was only observed at the zona surface (suggesting that it may be induced by zona components) and involved a vesiculation of sperm plasma and acrosomal membranes over the main body of the acrosome but not over the narrow, marginal region which persisted after the acrosome reaction was complete. Sperm penetration of the zona pellucida caused a large breach in the zona and the dispersal of perivitelline material. The fusion of the spermatozoon with the oolemma occurred first over the marginal acrosomal region and was accompanied by a fertilization cone which protruded through the zona penetration hole. Activation of the egg was characterized by the release of material from vesicles in the peripheral cytoplasm and extrusion of the second polar body. The mode of fertilization in Monodelphis was compared with what is known in other marsupials (New World and Australian) and eutherian (placental) mammals. It was concluded that the general features of the acrosome reaction and sperm-egg fusion may be essentially similar in both groups and that an evolutionary schism did not occur following the development of the eutherian mode of fertilization. PMID- 8214641 TI - Morphometric analysis of fetal rat lung development. AB - Applying the zone concept described previously, we quantitatively analyzed fetal rat lung development. The zone concept allowed us to coherently define reference spaces in the developing lung, a prerequisite for morphometric analysis. The peripheral zone I corresponds to a zone of growth of yet undifferentiated tissues; zone II arises from zone I and represents a region of structural and cellular differentiation; zones III and IV comprise the conducting airways and vessels. Lungs of fetal rats aged 17-23 days and 20 hours postnatal were fixed with OsO4 and glutaraldehyde and processed for light and electron microscopic morphometry implemented by point and intersection counting. Fetal lung volume grew in proportion to body weight. Zone II being the largest compartment, its volume changes largely determined lung growth rates. Zone II increased in mass owing to differentiation processes at the interface to zone I where the proximal portions of zone I were continuously shifted into zone II by differentiation. New tissue was generated within zone I. Due to these combined processes zone I changed little in volume until it disappeared at the end of the canalicular stage. The presence in the pseudoglandular stage of half of the parenchymal epithelial mass available around birth indicated that parenchymal development started earlier than assumed so far. While the endothelial surface increased most at birth, the epithelial surface grew by more than 600% at day 21, reflecting the onset of canalisation. The study confirmed the usefulness of the zone concept for morphometry and provided some new insights into lung development. PMID- 8214642 TI - Cell behaviors underlying notochord formation and extension in avian embryos: quantitative and immunocytochemical studies. AB - Formation and extension of the notochord is one of the earliest and most obvious events of axis development in vertebrate embryos. In birds, prospective notochord cells arise from Hensen's node and come to lie beneath the midline of the neural plate, where they assist in the process of neurulation and initiate the dorsoventral patterning of the neural tube through sequential inductive interactions. In the present study, we examined notochord development in avian embryos with quantitative and immunological procedures. Extension of the notochord occurs principally through accretion, that is, the addition of cells to its caudal end, a process that involves considerable cell rearrangement at the notochord-Hensen's node interface. In addition, cell division and cell rearrangement within the notochord proper contribute to notochord extension. Thus, extension of the notochord occurs in a manner that is significantly different from that of the adjacent, overlying, midline region of the neural plate (i.e., the median hinge-point region or future floor plate of the neural tube), which as shown in one of the previous studies from our laboratory (Schoenwolf and Alvarez: Development 106:427-439, 1989), extends caudally as its cells undergo two rounds of mediolateral cell-cell intercalation and two-three rounds of cell division. PMID- 8214643 TI - Light and electron microscopic analysis of two divisions of the suprachiasmatic nucleus in the young and aged rat. AB - The suprachiasmatic nucleus (SCN) is a principal controller of mammalian circadian rhythms. However, in spite of documented disturbance of biological rhythms in old animals, few significant age-related changes have been observed in this nucleus. This study examined age-related differences in SCN volume, neuronal number, density, and ultrastructural features in the entire rat SCN and in its two divisions, the denser ventromedial (compacta) and less dense dorsolateral (dissipata). Light and electron microscopic morphometric techniques were utilized in weanlings (21-28 days), young adults (3-6 mo), and aged (30-36 mo) animals. The total SCN volume, as well as volumes of the compacta region, were significantly greater in young adult and aged rats than in weanlings. Thus, as the rat ages the SCN increases in total size. However, the dissipata region appears to decrease in volume while the compacta increases. Even though the total number of SCN neurons was quite constant in the three age groups, the number of neurons in the dissipata region was decreased significantly in the young adult and aged groups as compared to the weanling. Neurons in the compacta region were usually spindled-shaped with two dendritic processes, while oval to spheroidal cells with 3-4 processes predominated in the dissipata. Nuclei of SCN cells were often invaginated. In weanlings, more SCN neuronal nuclei had invaginated nuclei in the dissipata region (66%) compared to the compacta (37%). In the two older age groups of rats, a higher percentage of invaginated neuronal nuclei were found in both regions. However, more were still found in the dissipata (90%) compared to the compacta (72%), even though the number of these cells in the compacta doubled. Thus, there was a large increase in the number of invaginated nuclei, as well as the number of invaginations, in the young adult rats compared to the weanling group, and this increase persisted in aged rats. SCN neurons usually had nuclei surrounded by a thin perimeter of cytoplasm containing sparse mitochondria and granular endoplasmic reticulum, multiple Golgi regions, and a moderate number of free ribosomes. In weanlings, mitochondria contained dense cristae and the granular endoplasmic reticulum was relatively prominent. Degenerative ultrastructural changes which included mitochondrial enlargement/vacuolation, Golgi vacuolation, lysosome, and lipofuscin development occurred in less than 10% of young adult SCN cells, and were more frequently found in the dissipata. In aged, rats 30% of the neurons showed degenerative changes in the dissipata compared with 18% in the compacta. Degenerative changes appeared highly correlated with the degree of membrane folding.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8214644 TI - Immunolocalization of collagen type I and laminin in the uterus on days 5 to 8 of embryo implantation in the rat. AB - This study investigated the immunohistochemical distribution of collagen type I and laminin during remodeling of the uterine extracellular matrix in response to embryo implantation in the rat. Collagen type I was found to be virtually absent around the embryo on the evening of day 5 of pregnancy. On days 6 to 8 of pregnancy the areas of primary and secondary decidualized tissue contained very little collagen in contrast to the outer nondecidualized stroma and myometrial tissues in which the staining patterns did not appear to alter. Day 8 of pregnancy was also notable for the appearance of collagen type I at the site of the developing placenta. Localization of laminin corresponded to areas of basement membrane and was associated with the redistribution of blood vasculature during implantation. By day 7 laminin staining was diminished in the basal areas of the lumenal epithelium around the implanting embryo. Laminin was also located in a punctate fashion at the margins of the primary decidual cells on day 6 of pregnancy, but by days 7 and 8 this staining pattern was no longer evident. This study has provided further evidence for a decline in a major fibrillar collagen during natural decidualization and also revealed a localized and transient expression of laminin in association with the differentiation of cells during primary decidual formation. PMID- 8214646 TI - Down-regulation and desensitization of the beta-adrenergic receptor system of human lymphocytes after cardiac surgery. AB - We used the beta-adrenergic receptor (beta AR) system of human lymphocytes as a model to examine perioperative adrenergic regulation in 12 patients undergoing coronary artery bypass grafting and 12 patients undergoing mitral or aortic valve replacement. beta AR function was assessed by measuring cyclic adenosine monophosphate (cAMP) production in the unstimulated state and in response to maximal stimulation by isoproterenol and prostaglandin E1. Receptor number and dissociation constant (KD) were assessed with [125I]iodopindolol. In the valve surgery patients, basal, isoproterenol-stimulated, and prostaglandin E1 stimulated cAMP production were significantly decreased postoperatively, by 39%, 55%, and 24%, respectively. beta AR number decreased from a mean of 1333 +/- 143 sites/cell to 897 +/- 56 sites/cell postoperatively, whereas the KD increased from 12.9 +/- 1.1 pM to 37.0 +/- 7.3 pM. In the coronary artery bypass graft patients, there were no significant alterations in cAMP production or receptor number, but the KD increased from 19.8 +/- 2.9 pM to 57.5 +/- 11.8 pM. These findings suggest that cardiac surgery and/or cardiopulmonary bypass may result in significant down-regulation and desensitization of the beta AR system of lymphocytes, which may parallel alterations in other organ systems. PMID- 8214645 TI - The publication of commercially sponsored supplements. PMID- 8214647 TI - Combined inotropic effects of amrinone and epinephrine after cardiopulmonary bypass in humans. AB - Amrinone, a phosphodiesterase inhibitor, and epinephrine, an alpha- and beta adrenergic receptor agonist, are inotropic drugs used during cardiac surgery to reverse myocardial depression after cardiopulmonary bypass. However, these drugs have not been compared separately, or in combination, in this patient population. We hypothesized that the combination might have complementary actions in improving myocardial function. We, therefore, compared amrinone, epinephrine, and the combination of amrinone and epinephrine in a randomized, blinded, placebo controlled study in patients undergoing coronary artery bypass grafting. Forty patients with ejection fractions > 0.45 were studied. Right ventricular ejection fraction pulmonary artery catheters and radial arterial catheters were inserted before fentanyl-midazolam anesthesia. After separation from bypass, patients received either a placebo (n = 20) or amrinone bolus (1.5 mg/kg, n = 20) at time 0 and a placebo (n = 20) or epinephrine (30 ng.kg-1.min-1, n = 20) infusion at time 5 min. This resulted in four study groups, n = 10 in each group. Data were collected every 2.5 min for 10 min. Epinephrine, amrinone, and the combination of both drugs significantly increased cardiac output, stroke volume, O2 delivery, and left ventricular stroke work. The increase in stroke volume (P < 0.05) was 12 +/- 6, 16 +/- 4, and 30 +/- 4 mL/beat with epinephrine, amrinone, and the combination of amrinone and epinephrine, respectively. The amrinone-epinephrine combination increased stroke volume as much as the sum of amrinone and epinephrine given separately. Systemic vascular resistance and pulmonary vascular resistance decreased with amrinone and amrinone-epinephrine, but not with epinephrine. Epinephrine increased mean arterial and mean pulmonary arterial pressures. Right ventricular ejection fraction did not significantly increase (P = 0.09) with epinephrine, but increased significantly with amrinone (0.45 to 0.53, P = 0.01), and with the combination (0.43 to 0.55, P = 0.006). These data indicate that amrinone and epinephrine effectively increase myocardial performance during cardiac surgery. Right ventricular function especially was improved with amrinone and the combination of amrinone and epinephrine. The combined effects of amrinone and epinephrine may be useful in patients recovering from the ischemia and reperfusion injury resulting from coronary artery bypass grafting. PMID- 8214648 TI - Comparison of bedside coagulation monitoring tests with standard laboratory tests in patients after cardiac surgery. AB - We compared portable bedside tests of whole blood coagulation with standard laboratory plasma coagulation tests to assess the accuracy and precision of the bedside tests in a clinical setting (postcardiac surgery). The Ciba Corning 512 Coagulation Monitor (Ciba Corning Diagnostics Corp., Medfield, MA) and the Hemochron 801 (International Technidyne Corp., Edison, NJ) were tested. One hundred forty-one patients who underwent cardiac surgery requiring cardiopulmonary bypass were evaluated upon arrival in the intensive care unit. Nine milliliters of fresh whole blood were used to obtain the prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and the heparin-neutralized thrombin time (HNTT) that were measured by bedside coagulation monitors. TT and HNTT were only measured by the Hemochron method. Blood from the same sample was also sent to the Hospital Stat Laboratory for simultaneous comparison of bedside results and standard coagulation tests. For PT and aPTT testing, an accuracy of +/- 10% and a precision of +/- 25% were considered clinically acceptable. Both of the PT tests met the dual criteria for clinical acceptability, but the aPTT tests did not meet either criterion. The difference between Hemochron TT and Hemochron HNTT correlated weakly, but significantly, with laboratory aPTT ratio (r = 0.52, P < 0.001). The slope of the regression line indicated that a TT-HNTT difference > 30 s correlated with an aPTT > 1.5 x control. We conclude that, in the postoperative cardiac surgical patient, PT was both accurate and precise in two commercially available tests, but aPTT was not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214649 TI - Myocardial metabolic and hemodynamic changes during propofol anesthesia for cardiac surgery in patients with reduced ventricular function. AB - This study examined the hypothesis that the use of propofol for induction and maintenance of anesthesia in patients with reduced ejection fraction (< 0.5) undergoing coronary artery revascularization would not be associated with a greater degree or incidence of myocardial ischemia as compared to patients receiving a moderate dose sufentanil-enflurane anesthetic technique. Two groups of patients were assigned randomly to receive one of two propofol anesthetic regimes. Group A (n = 21) received propofol 1-2 mg/kg as the induction drug and sufentanil 0.03 micrograms.kg-1.min-1 (fixed rate) plus propofol 50-200 micrograms.kg-1.min-1 (variable rate) infusions for maintenance of anesthesia. Group B (n = 21) received sufentanil 5 micrograms/kg for induction and propofol 50-200 micrograms.kg-1.min-1 (variable rate) infusion for maintenance of anesthesia. For comparison, a third group (Group C, n = 18) was studied subsequently. This group received sufentanil 5 micrograms/kg for induction of anesthesia which was maintained with enflurane. Adverse hemodynamic changes (hypertension, tachycardia) were managed by additional propofol (Groups A and B), sufentanil (Group C), or vasopressors (hypotension). Hemodynamic and myocardial metabolic profiles were measured when awake and sedated and at postinduction, postintubation, postincision, poststernotomy, and precardiopulmonary bypass times. Ischemia was assessed by measuring myocardial lactate production. The incidence of myocardial lactate production was reduced in Group B as compared to Group C (Group A, 45/126; Group B, 23/126; Group C, 58/107; P < 0.05). Myocardial lactate flux declined in all groups as surgery progressed; but apart from the reduction in flux (indicative of increased ischemia) noted in Group C versus Group B postinduction, no between-group differences were detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214650 TI - A comparison of propofol and etomidate for cardioversion. AB - Bolus doses of propofol in patients for cardioversion often produce hypotension and apnea. Etomidate provides cardiovascular stability in these patients, but myoclonus may interfere with electrocardiographic interpretation. This study was designed to demonstrate whether propofol, when given as a low-dose infusion, can attain etomidate's hemodynamic stability without its attendant side effects. Forty consenting patients were randomly assigned to receive either propofol infusion (50 mg/min) for induction of anesthesia followed by a maintenance infusion (100 micrograms.kg-1.min-1) or etomidate (8 mg/min and 20 micrograms.kg 1.min-1). Calculation of loading infusion rates for propofol and etomidate resulted in averages of 0.64 mg.kg-1.min-1 (range, 0.39-1.04) and 0.09 mg.kg 1.min-1 (range, 0.05-0.14), respectively. Induction times (2.2 min) and the times from terminating drug administration to awake states (4.5 min) were similar for each group. Etomidate produced myoclonus in 45% of the patients; otherwise side effects were minimal, with no significant differences between groups. The means of systolic blood pressures in the etomidate group rose a maximum of 15.3 +/- 7.9% (95% confidence), while a modest decrease of 7.2 +/- 7.3% occurred with propofol. Administration of propofol by infusion for cardioversion retains all its beneficial qualities while attenuating its hypotensive effects, making it a suitable choice for these patients with cardiac arrhythmias. PMID- 8214651 TI - Respiratory effects of intravenous morphine infusions in neonates, infants, and children after cardiac surgery. AB - We evaluated the respiratory effects of intravenous morphine infusions in 30 patients (2 to 570 days old, mean 155 days) after cardiac surgery. PaCO2 during spontaneous breathing and CO2 response curves during rebreathing were obtained on morphine infusions at drug steady state and during drug washout. Steady state morphine serum levels > 20 ng/mL resulted in hypercarbia (PaCO2 > 55 mm Hg) and depressed CO2 response curve slopes (< 10 mL.min-1.mm Hg ETCO2(-1).kg-1) in 67% and 70% of patients, respectively (P < 0.05, compared to those with levels < 20 ng/mL). During washout, morphine levels more than 15 ng/mL resulted in hypercarbia in 46%, whereas levels less than 15 ng/mL were associated with hypercarbia in 13% (P = 0.025). No age-related differences in respiratory effect were seen in these studies at the same serum morphine level. Careful observation of any patient receiving morphine remains necessary, but neonates and young infants seem to have the same respiratory response to morphine infusions as older infants and children at the same blood level. PMID- 8214652 TI - Blood conservation during pediatric cardiac surgery: ultrafiltration of the extracorporeal circuit volume after cardiopulmonary bypass. AB - After separation of pediatric patients from cardiopulmonary bypass (CPB), the authors salvaged red blood cells (RBCs) from the extracorporeal circuit by ultrafiltration and reinfused them to the patients. The purposes of this study were to determine 1) the effects of infusion of hemoconcentrated RBCs on hemoglobin, plasma free hemoglobin, and activated clotting time, and 2) the incidence of perioperative homologous RBC transfusion. Data were collected prospectively from 200 consecutive infants and children undergoing CPB during correction of congenital heart defects. The patients' hemoglobin, plasma free hemoglobin, and activated clotting time were measured both before and after infusion of 10 mL/kg of hemoconcentrate. Guidelines for intraoperative and postoperative transfusion of homologous RBCs were followed, and such transfusions were recorded. Significant increases in hemoglobin concentrations occurred when the hemoconcentrate was infused, as did statistically significant, but clinically manageable, increases in plasma free hemoglobin and activated clotting time. Perioperative homologous RBC transfusion was performed in 67% of patients (56% received intraoperative transfusion). Intraoperative transfusion was more frequent in small infants who were more hemodiluted by the clear CPB priming solution. Postoperative transfusion was more frequent in patients who had operation for cyanotic heart disease. Hemoconcentration by ultrafiltration after CPB is an effective and safe means of salvaging RBCs and reducing homologous RBC transfusion. PMID- 8214653 TI - Respiratory frequency and artifact affect the capnographic baseline in infants. AB - We sought to determine the effect of rebreathing on the capnographic waveform baseline. In anesthetized infants, we studied the effect of respiratory frequency (f) and breathing circuit type (Bain, n = 6, and pediatric circle, n = 4) on capnography of respiratory gas aspirated from the circuit for mass spectrometry (PCO2asp) and flowing through an infrared analyzer (PCO2f-t). As f increased, measured values of PiCO2asp and PiCO2f-t increased in both Bain and circle groups, with the exception of PiCO2f-t values that remained zero in the circle group. PETCO2 decreased as f increased in the circle groups, but remained constant in the Bain groups. These data suggest that artifact, most likely due to parabolic distortion of CO2 plugs traversing long sampling catheters, makes up a significant percentage (8%-36%) of the aspiration capnographic baseline elevation depending on f and breathing circuit type. Despite increases in PiCO2 as f increased, PETCO2 does not increase in Bain circuits due primarily to an increase in minute ventilation (Ve) that offsets the increase in the PiCO2 to provide balance in the CO2 mass relationship (PETCO2 approximately VCO2/Ve+PiCO2). These findings are useful in the correct interpretation of elevated capnographic baseline in infants. PMID- 8214654 TI - Clinical pharmacology of mivacurium in pediatric patients less than off years old during nitrous oxide-halothane anesthesia. AB - We determined the dose-response relationship of mivacurium in infants 2-6 and 7 11 mo of age during nitrous oxide-halothane anesthesia. The neuromuscular and cardiovascular effects of a bolus dose of mivacurium larger than the ED95 in infants and young children from 2-23 mo of age were observed. The infusion rate of mivacurium required to maintain approximately 95% neuromuscular block was determined. There was no significant difference between the estimated dose response relationship in infants 2-6 mo and that in infants 7-11 mo. The ED50 and ED95 were 44 micrograms/kg and 85 micrograms/kg for infants 2-11 mo (n = 70), r = 0.53. A bolus dose of 150 micrograms/kg mivacurium in infants (2-6 mo) produced 100% depression of the initial twitch height (T1) in 8 out of 9 infants and 85% depression in 1 infant. The time to onset of maximum block was 1.6 +/- 0.3 (0.7 2.7) (mean, SEM [range]) min, and time to recovery to 25% of T1 (T25) was 7.5 +/- 0.7 (5.5-11) min after 150 micrograms/kg in these patients. A bolus dose of 200 micrograms/kg mivacurium in infants and young children (7-23 mo) produced 100% depression of T1 in 14 of 17 patients, 97% depression in 2, and 90% depression in 1. The time to onset of maximum block was 1.5 +/- 0.1 (0.8-3) min and T25 was 10.3 +/- 1.5 (4.8-30.5) min after 200 micrograms/kg in these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214655 TI - Thermoregulatory response thresholds during spinal anesthesia. AB - Reportedly, during spinal anesthesia, the shivering threshold is reduced approximately 1 degree C but the vasoconstriction threshold remains normal. Such divergence between the shivering and vasoconstriction thresholds is an unusual pattern of thermoregulatory impairment and suggests that the mechanisms of impairment during regional anesthesia may be especially complex. Accordingly, we sought to define the pattern of thermoregulatory impairment during spinal anesthesia by measuring response thresholds. Seven healthy women volunteered to participate on two study days. On one day, we evaluated thermoregulatory responses to hypothermia and hyperthermia during spinal anesthesia; on the other day, responses were evaluated without anesthesia. Upper body skin temperature was kept constant throughout the study. The volunteers were warmed via the lower body and cooled by central venous infusion of cold fluid. The core temperatures triggering a sweating rate of 40 g.m-2 x h-1, a finger flow of 0.1 mL/min, and a marked and sustained increase in oxygen consumption were considered the thermoregulatory thresholds for sweating, vasoconstriction, and shivering, respectively. Spinal anesthesia significantly decreased the thresholds for vasoconstriction and shivering, and the decrease in each was approximately 0.5 degree C. The range of temperatures not triggering thermoregulatory responses (those between sweating and vasoconstriction) was 0.9 +/- 0.6 degree C during spinal anesthesia. The synchronous decrease in the shivering and vasoconstriction thresholds during spinal anesthesia is consistent with thermoregulatory impairment resulting from altered afferent thermal input. PMID- 8214656 TI - A comparative study of analgesia after knee surgery with intraarticular bupivacaine, intraarticular morphine, and lumbar plexus block. AB - Following arthroscopic surgery of the knee, 60 ASA I-II patients were randomly allocated to three different groups (n = 20 each) in an attempt to establish the best postoperative analgesic protocol: 20 ml of bupivacaine (0.25%; 50 mg) intra articularly (IA) (Group 1); continuous three-in-one lumbar plexus block using a catheter to administer 0.25 ml/kg of bupivacaine (0.25%; single-shot) plus continuous pump infusion of the same drug (0.03 ml.kg-1 x h-1 of 0.25% bupivacaine for 24 h) (Group 2); or 1 mg of morphine with 20 ml of saline IA (Group 3). The results were appraised in a double-blind manner, and the degree of postoperative pain was evaluated by visual analog scale (VAS) at constant hourly intervals for the first 24 h, by the incidence of secondary effects, and by the need for complementary analgesia. Group 2 (three-in-one) VAS values were lower 16 and 24 h after surgery and also globally (P < 0.05), with respect to the other two groups. Five patients in Groups 1 and 3 required complementary analgesia, while three patients in Group 1 suffered nausea. No other secondary effects were observed. We conclude that all three analgesic methods proved efficient, as reflected by the scant requirements for additional analgesics and the degree of expressed patient satisfaction. However, lumbar plexus block (three-in-one) with continuous bupivacaine infusion was most effective, and, although it constitutes an added technique, its scant complications and easy performance make its use advisable. PMID- 8214657 TI - A neurotoxicologic evaluation of the spinal cord after chronic intrathecal injection of R-phenylisopropyl adenosine (R-PIA) in the rat. AB - Studies in animals have shown that the adenosine receptor agonist R phenylisopropyl adenosine (R-PIA) induces antinociceptive effects after intrathecal administration. Before such a potentially antinociceptive drug could be considered for intrathecal injection in humans, a neurotoxicologic examination of the spinal cord must be performed in animal models. Rats were injected once every day for 14 consecutive days with R-PIA or saline (controls). The number and density of neuronal cells were calculated by using light microscopy, and further examined with electron microscopy. The "disector method," which is an unbiased stereologic estimator of cell number and mean cell volume, was used for quantitative morphometric analyses. With this technique no significant changes could be seen in rats that had received R-PIA as compared to control rats. We conclude that no significant histologic changes could be detected after chronic intrathecal administration of R-PIA. PMID- 8214658 TI - Segmental wall motion abnormalities in patients undergoing total hip replacement: correlations with intraoperative events. AB - We examined the effect of methylmethacrylate cement on venous embolization and cardiac function in 20 patients having total hip arthroplasty under general anesthesia. Segmental wall motion abnormalities and intracardiac targets (presumably emboli) were investigated by making videotaped recordings of the transgastric short axis and longitudinal 4-chamber views of the heart with transesophageal echocardiography at different points during surgery. The incidence of segmental wall motion abnormalities was the most frequent during insertion of cemented femoral prostheses (8 of 14 patients had wall motion abnormalities). This was significantly different from baseline measurements taken at the beginning of surgery (P < 0.05). In addition, there were also significantly more segmental wall motion abnormalities in patients having a cemented femoral component compared to those having an uncemented femoral prosthesis (P < 0.05). The incidence of wall motion abnormalities during acetabular and femoral reaming and during wound closure was not significantly different from baseline. Intracardiac targets (emboli) were seen in all 20 patients during surgery. The largest number of emboli occurred during reaming of the femur and during insertion of the femoral prosthesis. Significantly more emboli were seen with cemented components (P < 0.02). Most emboli were small (< 2 mm) and appeared similar to the microbubbles produced by agitating saline with a small amount of air. Six patients also had larger (> 5 mm) emboli that appeared to be solid material. One patent foramen ovale was detected (5% incidence). There were no adverse cardiac or neurologic events, and heart rate and arterial blood pressure remained within normal limits throughout surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214659 TI - Previous administration of indomethacin or naloxone did not influence ketorolac antinociception in mice. AB - We studied the effects of the inhibition of prostaglandin biosynthesis and opioid antagonism in the antinociceptive action of ketorolac using the mouse acetic acid writhing test. Ketorolac was administered via the intraperitoneal, intrathecal, or intracerebroventricular routes. Although the ketorolac induced a significant dose-dependent antinociceptive effect, the intracerebroventricular administration was the most effective route. Indomethacin and naloxone pretreatments did not change the ketorolac-induced antinociception. The present findings suggest that this antinociceptive action of ketorolac is not mediated by the inhibition of prostaglandin biosynthesis nor by activation of opioid receptors. PMID- 8214660 TI - Pathogenesis of gastric particulate lung injury: a comparison and interaction with acidic pneumonitis. AB - Experimental aspiration pneumonitis studies in general have focused on the pathogenesis of the acidic component of the lung injury, although the injury produced by the particulate component of gastric contents largely has been ignored. The present study compares the inflammatory potential of small gastric particles to acidic lung injury and examines their interaction. Washed and filtered rat gastric food particles, 2-30 mu were resuspended in saline/HCl, pH = 5.3 or 1.25 at different particle densities and instilled intratracheally into anesthetized rats. Nonlethal lung injury was assessed at different times postaspiration by measuring changes in lung permeability and histology. Maximal survival after lung injury in this model occurred at a particle concentration of 40 mg/mL and at a volume of 1.5 mL/kg. Under these conditions, the alveolar capillary leak was less severe during the first 4 h after injury than that seen with a maximal nonlethal acidic injury (1.5 mL/kg, pH = 1.25). However, after 4 h postinjury the alveolar capillary leak increased to levels that were no different from the acidic injury. When the small gastric food particles were suspended in saline/HCl, pH = 1.25, the alveolar capillary leak was increased synergistically. Intratracheal instillation of inert, 10 mu (glass) particles, 40 mg/mL at 1.5 mL/kg, did not result in an increase in lung injury or interact additively or synergistically with acidic saline. Histologically, the small gastric particle injured lungs were associated with focal inflammatory changes as the acidic damage was diffuse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214661 TI - Nitrous oxide decreases solubility of isoflurane and halothane in blood. AB - This study investigated the effects of carrier gases on the solubility of isoflurane or halothane in blood. The blood/gas partition coefficients (lambda blood/gas) of 1 minimum alveolar anesthetic concentration of isoflurane or halothane in 100% oxygen, 30% oxygen with 70% nitrous oxide, 100% nitrous oxide or air were measured at 37 degrees C, with blood from four donors. The values of isoflurane or halothane in 100% nitrous oxide (1.42 +/- 0.03; 2.59 +/- 0.05) were lower (P < 0.05) than those obtained when using 100% oxygen (1.53 +/- 0.02; 2.71 +/- 0.05) or air (1.54 +/- 0.03; 2.74 +/- 0.05). To determine the effect of absence of oxygen in the blood containing nitrous oxide on solubility, lambda blood/gas of 1 minimum alveolar anesthetic concentration of isoflurane or halothane in 100% oxygen, a gas mixture (30% oxygen and 70% nitrous oxide) or 100% nitrous oxide were measured under the same conditions. The values of isoflurane or halothane in 100% nitrous oxide (1.29 +/- 0.03; 2.25 +/- 0.08) and in a gas mixture of 30% oxygen and 70% nitrous oxide (1.33 +/- 0.04; 2.29 +/- 0.05) were lower (P < 0.05) than those obtained with 100% oxygen (1.40 +/- 0.03; 2.37 +/- 0.04). We conclude that nitrous oxide decreases the lambda blood/gas of isoflurane or halothane, and that this change of solubility, although small, increases the uptake rate of halothane or isoflurane. PMID- 8214662 TI - Growth of Staphylococcus aureus in four intravenous anesthetics. AB - Patient infections related to the use of propofol have been reported. To investigate the growth of Staphylococcus aureus in propofol, thiopental, methohexital, etomidate, and 0.9% saline containing no bacteriostatic drug, these preparations were inoculated and samples were plated onto blood agar at 0, 3, 6, 21, 24, and 27 h. The number of colony-forming units (CFU) on the plates was then determined after 24 h of incubation. Samples from the inoculated etomidate solution showed zero CFU at 3 h and thereafter, whereas 21 h were required by the methohexital and thiopental solutions to reduce the number of CFU to zero. For normal saline, no significant change in CFU was seen before the first 6 h, then the number of CFU gradually declined, although some S. aureus CFU were still present at 27 h. Inoculation of the propofol emulsion resulted in a substantial growth of S. aureus between 6 and 21 h after inoculation. We conclude that, of the preparations tested, only propofol was an excellent medium for the rapid growth of S. aureus. Meticulous sterile technique, therefore, is advised when handling it. PMID- 8214663 TI - Anesthesia-induced modulation of in vivo antibody levels: a study of pentobarbital, chloral hydrate, methoxyflurane, halothane, and ketamine/xylazine. AB - The influence of anesthesia on long-term changes in in vivo antibody levels after antigen challenge was examined. Rats experienced a surgical plane of various anesthetics alone (anesthesia/intact) or in combination with laparatomy (anesthesia/laparatomy) and were given 1 or 3 wk to recover. Antigen, keyhole limpet hemocyanin, was then administered, and antibody levels specific to the antigen were measured during the next 14 days. Comparisons were made between anesthesia-treated animals and home cage controls. Pentobarbital and chloral hydrate produced decreases in in vivo antibody levels even 3 wk after exposure, whereas halothane, methoxyflurane, and ketamine/xylazine did not. Ketamine/xylazine produced moderate but not significant decreases in antibody levels when 1 wk intervened between exposure and antigen administration, but not when 3 wk intervened. Surgery did not produce larger changes in antibody levels than did anesthesia itself. These data suggest the possibility that some anesthetics, per se, may contribute to infection that may occur postoperatively. PMID- 8214664 TI - The orbicularis oculi and the adductor pollicis muscles as monitors of atracurium block of laryngeal muscles. AB - The aim of this study was to determine whether atracurium-induced neuromuscular block at the laryngeal adductor muscles could be predicted by visual inspection of either adductor pollicis or orbicularis oculi responses. Twenty-one ASA Class I or II patients were anesthetized with propofol (2-2.5 mg/kg) and fentanyl (2-5 micrograms/kg). Tracheal intubation was performed without neuromuscular blocking drugs. Patients were assigned randomly to receive atracurium 0.3 or 0.5 mg/kg intravenously. Train-of-four stimulation was applied to the ulnar, facial, and recurrent laryngeal nerves. Laryngeal response was measured as the pressure change in the tracheal tube cuff positioned between the vocal cords. The response at the adductor pollicis and orbicularis oculi was evaluated visually by two observers who detected if and when block was complete. Twelve patients, including all those receiving 0.5 mg/kg, had complete orbicularis oculi block. The same patients, except one, also had 100% laryngeal block. Adductor pollicis response was abolished in the same 12 patients plus an additional 4 patients. In patients receiving atracurium 0.5 mg/kg, laryngeal and orbicularis oculi responses were abolished faster (mean +/- SD: 132 +/- 80 and 146 +/- 58 s, respectively) than the adductor pollicis muscle (243 +/- 55 s; P < 0.05). There was a significant correlation (r = 0.94; P < 0.001) between neuromuscular block onset time at the laryngeal adductor and orbicularis oculi muscles but not between laryngeal and thumb muscles. The authors conclude that, after injection of atracurium, laryngeal adductor and orbicularis oculi blocks have similar intensities and time courses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214665 TI - Interaction between famotidine and neuromuscular blockers: an in vivo study in rats. AB - The effect of histamine 2-antagonist famotidine on neuromuscular paralysis induced with either nondepolarizing or depolarizing neuromuscular blocking drugs was examined in anesthetized and mechanically ventilated rats. Neuromuscular paralysis, as judged by tibialis anterior muscle twitch tension in response to sciatic nerve stimulation, was maintained at about 50% with intravenous bolus and infusion regimens of either atracurium, gallamine, succinylcholine, or decamethonium. Famotidine, 0.1, 1, and 4 mg/kg, intravenously, were then administered at 5-min intervals as the infusion of the neuromuscular blocker was continued. Famotidine at any of these three doses failed to alter the steady state neuromuscular paralysis produced with either atracurium (prefamotidine versus final postfamotidine paralysis (mean +/- SE depression of twitch tension, n = 6, 49.8 +/- 2.8 vs 51.5 +/- 2.6%), gallamine (47.8 +/- 1.6 vs 47.6 +/- 3.0%), succinylcholine (49.2 +/- 1.8 vs 49.4 +/- 2.0%), or decamethonium (50.3 +/- 2.1 vs 51.5 +/- 2.0%). Intravenous famotidine at human therapeutic doses, fails to alter neuromuscular function in vivo in rats. PMID- 8214666 TI - Metoclopramide decreases thiopental hypnotic requirements. AB - We compared the effect of metoclopramide (MCA) with droperidol (DPD) on thiopental hypnotic requirements in 96 unpremedicated female patients. The study was randomized, double-blind, and placebo-controlled. The response to the verbal command was used as an end-point of anesthesia. Two methods of determination of thiopental hypnotic requirements were used: titration (infusion of thiopental at a rate of 0.5 mg.kg-1 x min-1) until the end-point was reached and construction of the dose-response curve based on bolus injections of predetermined doses of thiopental (with the use of probit analysis). The ED50 value of thiopental determined by probit analysis was reduced after the 0.2 mg/kg MCA administration by 44% (P < 0.0001). The thiopental hypnotic requirements obtained with the titration method were as follows: 5.3 +/- 0.3 mg/kg in control, 4.5 +/- 0.2 mg/kg (delta 14%, P < 0.03) with 0.1 mg/kg MCA, 3.2 +/- 0.2 mg/kg (delta 39%, P < 0.0001) with 0.2 mg/kg MCA, and 2.9 +/- 0.2 mg/kg (delta 45%, P < 0.0001) with 0.4 mg/kg MCA. DPD decreased thiopental hypnotic requirements almost to the same degree as MCA, with the ceiling effect observed at doses of 0.01 and 0.02 mg/kg (delta 44%, P < 0.0001). The results indicate that MCA causes a profound decrease in thiopental hypnotic requirements. The similarity between the thiopental sparing effects of MCA and DPD suggests that the blockade of D2 receptors is the main mechanism underlying this effect. PMID- 8214667 TI - A new model to evaluate the hypertensive response to noxious stimuli in the anesthetized, spontaneously hypertensive rat. AB - We have developed a method to evaluate the hypertensive response after noxious stimuli in anesthetized rats. Anesthetic level, stimuli, and responses were standardized by using an etomidate infusion, a series of stimuli of increasing intensity applied to the tail, and measuring maximal changes in systolic blood pressure (delta SBP) after each stimulus. Normotensive Sprague Dawley rats (SD) (n = 7) were studied using an etomidate infusion of 4.2 mg.kg-1 x h-1. This method was then applied to spontaneously hypertensive rats (SHR) anesthetized with three rats of etomidate infusion: Group 1 (n = 8), 7.0 mg.kg-1 x h-1; Group 2 (n = 8), 5.6 mg.kg-1 x h-1; and Group 3 (n = 11), 4.2 mg.kg-1 x h-1. Under anesthesia, three types of noxious stimuli were applied to the tail at 1-min intervals (13 total): (a) Type 1:11 2-s electrical stimuli of increasing intensity (0.4-12 mA, to produce threshold to maximal responses); (b) Type 2: one intense, prolonged electrical stimulus (10 mA, 5 s); and (c) Type 3: tail clamping. After each stimulus, delta SBP was measured. In the SHR, comparing single delta SBP responses to single noxious stimuli after each of the three most intense stimuli showed no statistically significant differences among the three anesthetic groups. In contrast, comparison of dose-response curves of multiple delta SBP responses to multiple Type 1 (2-s) stimuli demonstrated a significant difference among the three anesthetic groups of SHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214668 TI - Neuroprotective doses of N-methyl-D-aspartate receptor antagonists profoundly reduce the minimum alveolar anesthetic concentration (MAC) for isoflurane in rats. AB - N-methyl-D-aspartate (NMDA) receptor antagonists, which block one of the glutamate receptors, have provided evidence of cerebral protection in animal models of focal cerebral ischemia. We examined the effect of neuroprotective doses of one noncompetitive (dizocilpine) and two competitive (D-CPP-ene, CGS 19755) NMDA antagonists on the minimum alveolar anesthetic concentration (MAC) of isoflurane in rats. A single bolus injection of any of the three NMDA antagonists produced a significant (P < 0.01) and sustained (> 3 h) decrease in the MAC of isoflurane. Dizocilpine decreased MAC by 33%-38% at a dose of 0.15 mg/kg and 48% 54% at a dose of 0.5 mg/kg. D-CPP-ene decreased MAC by 32%-37% at a dose of 1.5 mg/kg and 39%-45% at a dose of 4.5 mg/kg. CGS 19755 decreased MAC by 19%-24% at a dose of 3 mg/kg and 49%-58% at a dose of 10 mg/kg. Dizocilpine, but not the competitive antagonists, produced a small transient decrease in mean arterial blood pressure. The sustained anesthetic potency of neuroprotective doses of NMDA antagonists supports the idea that glutaminergic receptor activity is involved in determining the anesthetic state. PMID- 8214669 TI - Predictive accuracy of continuous alfentanil infusion in volunteers: variability of different pharmacokinetic sets. AB - To evaluate the variability of the predictive accuracy of alfentanil by using different pharmacokinetic data sets, eight healthy young male adult volunteers were given the same alfentanil infusion for 4 h. Nineteen venous blood samples were taken from each volunteer, and alfentanil concentrations were titrated by radioimmunoassay. For each volunteer, the pharmacokinetic variables of a two compartment model were calculated, averaged, and considered as a reference set. Based on the infusion profile given to the volunteers, central compartment concentrations were calculated by using the reference set and nine previously published pharmacokinetic sets of alfentanil concentrations in healthy adults. The bias, inaccuracy, and dispersion of each data set were assessed by determining the median performance error, the median absolute performance error (MDAPE) and the 10th and 90th percentiles, respectively. By using the pharmacokinetic variables of the volunteers, the predictive accuracy was excellent (MDAPE, 7.25%). Among the 10 averaged pharmacokinetic sets, there was a significant correlation between their bias and clearance (R2 = 0.996). The reference set had the best predictive accuracy (MDAPE, 23.6%). Five sets from the literature also showed a reliable predictive accuracy but four other sets with a clearance more than 5 mL.kg-1.min-1 and derived from a large bolus injection were inaccurate (MDAPE > 50%) as they underestimated the alfentanil concentrations. We conclude that pharmacokinetic sets derived from large bolus should not be selected to accurately predict alfentanil infusion. PMID- 8214670 TI - The direction dependence of thermoregulatory vasoconstriction during isoflurane/epidural anesthesia in humans. AB - We tested the hypothesis that once thermoregulatory vasoconstriction is triggered at a given core temperature during isoflurane anesthesia, redilation starts at a substantially higher core temperature. To avoid direct perception of cutaneous cooling and warming, we used epidural anesthesia and limited our thermal manipulations to the blocked area. Seven volunteers were anesthetized with isoflurane/epidural anesthesia (approximately T9 dermatomal level). Core hypothermia was induced by surface cooling restricted to the legs. Cooling was continued until fingertip blood flow suddenly decreased (vasoconstriction threshold). The core was then rewarmed by heating the legs until fingertip flow suddenly increased toward initial values (redilation threshold). The difference between the two thresholds defined the direction-dependent hysteresis. Vasoconstriction occurred at 35.2 +/- 0.6 degrees C and vasodilation at 36.2 +/- 0.5 degrees C (P < 0.01, paired t-test); consequently, the hysteresis was 1.0 +/- 0.6 degrees C. The observed hysteresis suggests that thermoregulatory responses during combined isoflurane/epidural anesthesia are not determined simply by instantaneous thermal input to central controllers, but may also depend on the direction of core temperature change. PMID- 8214671 TI - Renal function after sevoflurane or enflurane anesthesia in the Fischer 344 rat. AB - Sevoflurane is metabolized to inorganic fluoride, a potential nephrotoxin. To evaluate the nephrotoxic potential of sevoflurane, 1-yr-old male Fischer 344 rats were anesthetized with 10 minimal alveolar anesthetic concentration (MAC) h sevoflurane or enflurane with or without pretreatment with biotransformation enhancing agents. Peak serum fluoride levels reached 35 microM with sevoflurane anesthesia after pretreatment with phenobarbital and 40 microM after enflurane anesthesia after pretreatment with isoniazid. One day after anesthesia, sevoflurane-anesthetized rats concentrated urine normally in response to subcutaneous administration of 1-deamino-8-D-arginine vasopressin and exhibited no increase in urinary excretion of N-acetyl beta-glucosaminidase. Isoniazid treated, enflurane anesthetized rats developed a 31% reduction in maximal urinary concentrating ability and a 3.5-fold increase in excretion of N-acetyl-beta glucosaminidase. Sevoflurane produced no evidence of fluoride-induced nephrotoxicity in noninduced or enzyme-induced rats. Under similar conditions, enflurane produced laboratory evidence of nephrotoxicity. PMID- 8214672 TI - G proteins: basic characteristics and clinical potential for the practice of anesthesia. PMID- 8214673 TI - Cocaine abuse in the parturient and effects on the fetus and neonate. AB - The growing use of cocaine among pregnant women and women of childbearing age has become an issue of great concern to physicians. Cocaine abuse among parturients is associated with multi-target organ involvement, including the cardiovascular, respiratory, neurologic, and hematologic systems. Cocaine use during pregnancy is also an independent contributor to the risk of placental abruption, preterm labor, precipitate delivery, stillbirth, and others. Although a history of premature rupture of membranes, smoking, alcohol use, syphilis serology, and use of other illicit drugs suggests cocaine abuse, the single most important predictor is the absence of prenatal care. The intraoperative anesthetic management should take into consideration the different effects of cocaine on the mother, the fetus, and the neonate. PMID- 8214674 TI - Prevention of cautery-induced airway fires with special endotracheal tubes. PMID- 8214675 TI - Are we obsessed with masseter muscle rigidity? Temporomandibular joint disease mistakenly diagnosed as masseter muscle rigidity on two separate occasions in one patient. PMID- 8214676 TI - Spinal anesthesia in a patient with hyperthyroidism due to hydatidiform mole. PMID- 8214677 TI - Awake, blind nasotracheal intubation for cesarean section in a patient with autoimmune thrombocytopenic purpura and iatrogenic Cushing's syndrome. PMID- 8214678 TI - Upper airway obstruction and Menkes syndrome. PMID- 8214679 TI - Transesophageal echocardiography-guided pulmonary artery catheter placement. PMID- 8214680 TI - Hyponatremia and possible uterine perforation during endometrial rollerball ablation. PMID- 8214681 TI - Propofol and the patient with hereditary coproporphyria. PMID- 8214682 TI - Saline versus water for epidural injection. PMID- 8214683 TI - Dental appliances can complicate an otherwise normal airway. PMID- 8214684 TI - Concealed illegal drugs: an actual cause of airway obstruction. PMID- 8214685 TI - Volatile anesthetics and myocardial stunning. PMID- 8214686 TI - Epinephrine in local anesthetics does indeed produce hypokalemia and ECG changes. PMID- 8214687 TI - Glucose-insulin-potassium regimes during cardiac surgery. PMID- 8214688 TI - Supramaximal second gas effect--a nonexistent phenomenon. PMID- 8214690 TI - Central venous access--a potential hazard with insertion needle! PMID- 8214689 TI - Epidural blood patch for Jehovah's Witness patient. PMID- 8214691 TI - The initial clinical experience of 1819 physicians in maintaining anesthesia with propofol: characteristics associated with prolonged time to awakening. AB - In October 1989, propofol underwent Phase IV Food and Drug Administration testing that involved 25,981 patients, 1722 institutions, and 1819 anesthesiologists. Participants were 18-80 yr of age and ASA physical status I-III; they could not have a continuing pregnancy or prior adverse anesthetic experience. Anesthesiologists completed detailed forms to describe their use of propofol in this three-step study: propofol for induction only (Step 1), for induction and then maintenance by intermittent bolus injection (Step 2), or for continuous infusion (Step 3). In early 1992, our group of anesthesiologists and epidemiologists analyzed the resulting data base. We evaluated data from 14,882 patients (8095 given bolus injections and 6787 given continuous infusion) to determine factors predicting prolonged time (> 15 min after cessation of all anesthesia) to awakening, one measure of recovery from anesthesia. The incidence of prolonged awakening was 6.8% (1016 patients); the median and mean (+/- SD) times to awakening were, respectively, 5 min and 7.2 +/- 7.3 min. The following variables were associated (P < 0.05) with prolonged awakening from propofol maintenance anesthesia: a total dose of propofol > 8 mg/kg, male gender, endotracheal intubation, age > 65 yr, abdominal surgery, continuous infusion of propofol, and concomitant use of isoflurane or benzodiazepines. These results support the clinical impression that recovery from propofol anesthesia is remarkably rapid; although the vast majority of physicians participating in this study were using propofol for maintenance for the first time, only 6.8% of patients had awakening times exceeding 15 min. PMID- 8214692 TI - Effects on recovery when isoflurane is used to supplement propofol-nitrous oxide anesthesia. AB - During propofol-nitrous oxide (N2O) anesthesia, volatile anesthetics are frequently administered to treat signs of inadequate anesthesia and to decrease the possibility of intraoperative awareness. Because the clinical effects of this combination have not been examined rigorously, we used data from the 1989-90 Phase IV clinical trial with propofol to evaluate recovery from propofol-N2O anesthesia with and without supplementation with isoflurane. In this study involving 15,806 patients at 1722 institutions, propofol was administered for induction and maintenance of anesthesia with N2O for procedures lasting less than 60 min. At the discretion of the anesthesiologist, volatile anesthetics were administered as needed during maintenance of anesthesia (the incidence of use of inhaled anesthetics was 14.7% for isoflurane, 2.2% for enflurane, and 0.2% for halothane). Other intraoperative medications included opioid analgesics, muscle relaxants, and anticholinergic drugs. The present study concerns the subset of 7796 patients given propofol-N2O maintenance anesthesia (intermittent bolus or continuous infusion) with or without isoflurane supplementation for procedures lasting less than 60 min. Isoflurane was used more frequently for procedures lasting 30-60 min than for those less than 30 min. Nevertheless, the maintenance dose of propofol was significantly (P < 0.05) less with isoflurane (178 vs 235 mg). Adjunctive use of isoflurane prolonged the time to awakening and to becoming oriented, but discharge times were similar for the two groups. The incidence of postoperative nausea, vomiting, recall, and excitement did not differ between the two groups. We conclude that the addition of isoflurane to a propofol-N2O anesthetic does not alter recovery from anesthesia. PMID- 8214693 TI - Hemodynamic effects of propofol: data from over 25,000 patients. AB - To investigate clinically important hypotension and bradycardia after induction of anesthesia with propofol, we analyzed data from a Phase IV stepwise study involving 25,981 patients, 1722 institutions, and 1819 anesthesiologists. In Step 1, propofol was used for induction only. In Step 2, propofol was used for induction and then maintenance by intermittent injection. In Step 3, an induction dose was followed by a maintenance infusion. Participants were to be 18-80 yr of age and ASA physical status I-III; they could not have a continuing pregnancy or prior adverse anesthetic experience. Detailed data on demographic, perioperative, and outcome variables were recorded on data collection forms. The overall incidence of hypotension (systolic blood pressure < 90 mm Hg) was 15.7%; 77% of the episodes were recorded within 10 min of induction of anesthesia with propofol. Bradycardia (heart rate < 50 beats/min) occurred in 4.8% of patients, with 42% of the episodes in the first 10 min. Only 1.3% of patients had both hypotension and bradycardia. The incidence of hypotension was significantly higher for the elderly, females, Caucasians, those undergoing abdominal and integumentary procedures, and those given propofol with opioids, benzodiazepines, or propranolol. Bradycardia was significantly more common when propofol was combined with opioids or chronically taken beta-adrenergic receptor-blocking drugs. Bradycardia and hypotension were not commonly associated. Giving this new drug by protocol, even inexperienced anesthesiologists incurred few adverse hemodynamic changes. Hemodynamic changes were transient and rarely (< 0.2%) required drug therapy. Cardiovascular changes and drug interactions were predictable and manageable based on knowledge of the pharmacology of propofol. PMID- 8214694 TI - Adverse events in a multicenter phase IV study of propofol: evaluation by anesthesiologists and postanesthesia care unit nurses. AB - Phase II and III studies are tightly controlled trials investigating adverse effects before government approval of a new drug. However, because postapproval Phase IV studies involve a much larger and more complex population, the true nature of adverse effects can be seen. We analyzed Phase IV data for the new drug propofol with regard to the incidence of adverse events, and evaluations of such events by anesthesiologists versus postanesthesia care unit (PACU) nurses. Data pertained to 25,981 patients, 1722 institutions, and 1819 anesthesiologists giving propofol in three anesthetic regimens. Inclusion criteria were liberal: age, 18-80 yr; ASA physical status I-III; no continuing pregnancy; and no prior adverse anesthetic experience. Anesthesiologists and PACU nurses used data collection forms to record demographic, perioperative, and outcome variables; to evaluate recovery (excellent, good, or poor); and to describe adverse events. Adverse events were reported for 2813 patients (10.8%); the most common events were pain on injection (5.2%), hypotension (1.1%), nausea/vomiting (1.9%), and excitement (1.3%). The incidences of pain on injection and nausea/vomiting were approximately one-half and one-fifth, respectively, the values reported in earlier studies. Six hundred thirty-three patients (2.4%) had a "poor" recovery according to one or both of the evaluators (the anesthesiologist or PACU nurse). The PACU nurse was more influenced by nausea, vomiting, or postoperative pain; and the anesthesiologist was more influenced by postoperative confusion or delayed emergence from anesthesia. For only 0.6% of patients did both evaluators rate recovery as poor. Anesthesiologists gave more weight to intraoperative adverse events, and nurses to postoperative events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214695 TI - How do anesthesiologists select patients when introducing a new drug into practice? AB - As part of the marketing strategy for the anesthetic drug propofol (Diprivan), Stuart Pharmaceuticals began a Phase IV postmarketing study soon after the drug received Food and Drug Administration approval in 1989. We used data from this study to test the hypothesis that anesthesiologists would initially use propofol for young, relatively healthy patients and then, with experience, for older, sicker patients. The Phase IV study involved 1722 institutions, 1819 anesthesiologists, and 25,981 patients. The study incorporated three sequential steps, each to be tested in five patients. In Step 1, propofol was used for induction only; in Step 2, for induction and maintenance of anesthesia by intermittent injection; and, in Step 3, for induction and maintenance by continuous infusion. Inclusion criteria were age 18-80 yr and ASA physical status I-III. Exclusion criteria were continuing pregnancy and a previous adverse anesthetic experience. Physicians used standardized data collection forms to voluntarily compile detailed demographic, perioperative, and outcome variables for patients. Data were then evaluated by an independent, multicenter team of seven anesthesiologists and three epidemiologists to determine whether the first two patients selected to participate in each step (Patients 1 and 2, 6 and 7, and 11 and 12) were less sick, younger, or undergoing less invasive or shorter procedures than patients enrolled later in the same steps (Patients 4 and 5, 9 and 10, and 14 and 15). Physicians gave propofol first to patients with fewer concurrent diseases than are found in the general population (10% were hypertensive versus 16%; 3% were diabetic versus 10%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214696 TI - Phase IV study of propofol: validation of the data set. AB - In 1989-1990, Stuart Pharmaceuticals conducted a Phase IV study of propofol on over 26,000 patients, later making the large data base available to a team of epidemiologists and anesthesiologists for analysis. We now describe the process of verifying the data to provide a sound basis for further analyses. Original data were collected by 1819 physicians at 1761 hospitals. In that study, anesthesia was induced by bolus injection of propofol and was maintained by inhaled drug and N2O-O2 (Step 1), or by propofol (either intermittent bolus injection [Step 2] or continuous infusion [Step 3]) and N2O-O2. Forty-six recorded variables described history, physical examination, course and quality of anesthesia and recovery, and adverse events. Data were scrutinized for inaccuracy or bias regarding adverse events, completeness of data, data entry, and violations of the study protocol. The initial data set pertained to 26,841 patients (10,698, Step 1; 8886, Step 2; and 7257, Step 3). Because we excluded data if 25% of the items were missing from the data set, 3.2% of the case reports were eliminated: the final data set used for subsequent analyses contained 25,981 patients (10,184, Step 1; 8672, Step 2; and 7125, Step 3). Inaccuracy of data entry was not excessive, and violations of study protocol were less frequent than in similar studies. The nature and frequency of adverse events were similar to those reported in Phase II and III clinical trials of propofol. Analysis showed that missing data occurred randomly and did not introduce obvious bias. We conclude that the data set was valid and most likely represents perioperative events occurring in similar patients; that Phase IV studies can be valuable because of the range of patients studied and the ability to detect even rare events; and that future Phase IV studies could be improved by more efficient design of data collection forms for both hypotheses to be tested and the entry of data onto forms. PMID- 8214697 TI - The role of pharmacoepidemiology research in postmarketing surveillance and anesthesia practice/critical care medicine. AB - Despite tremendous efforts to ensure the safety and effectiveness of newly marketed medications, a number of these have had significant problems after introduction of the drug to the market. Such problems highlight the practical limitations of clinical trials performed to obtain FDA approval for marketing. Pharmacoepidemiology research methodologies provide a powerful mechanism for exploring the determinants of drug safety and effectiveness in broad-based populations and can serve as a scientific foundation for outcome research. Using these methodologies, largescale postmarketing surveillance studies similar to the type described in the accompanying articles would constitute an important way of confirming and identifying the determinants of drug safety and effectiveness in large, diverse patient populations. PMID- 8214698 TI - Concentration-effect relationships of propofol after total intravenous anesthesia. AB - To evaluate the concentration-effect relationships of propofol during recovery after total intravenous anesthesia, 20 female patients undergoing lower abdominal surgery were studied. In 10 patients (Group B) the propofol infusion was supplemented with an epidural block with bupivacaine to evaluate the relation between the blood concentration of propofol and various pharmacodynamic end points. The remaining 10 patients (Group A) received an alfentanil infusion intravenously instead of the epidural block to assess the dynamic interactions of alfentanil and propofol. Postoperative performances (drowsiness, amnesia, cooperation, and orientation) were evaluated by means of scoring scales. Critical flicker fusion threshold (CFF) also was used to assess the level of postoperative alertness. A propofol blood concentration of 2.5 micrograms/mL was required for satisfactory hypnosis during surgery and at 0.8 +/- 0.4 microgram/mL, the patients were considered fully awake. A concomitant alfentanil infusion reduced the propofol concentration required by 0.2-0.4 microgram/mL for the same degree of effect. Rapid recovery was seen in all patients, but in the group receiving alfentanil infusion there was a shift to the left of the concentration-effect curve in regard to drowsiness and a statistically significant prolongation of recovery by CFF-measurement which suggests a possible dynamic interaction with alfentanil. We conclude that there is a good correlation between the blood concentration of propofol and the pharmacodynamic responses during recovery. PMID- 8214700 TI - Cerebral awakening concentration of sevoflurane and isoflurane predicted during slow and fast alveolar washout. AB - We studied 49 patients of ASA physical status I to determine cerebral anesthetic concentration on awakening calculated with end-tidal anesthetic concentration, when the end-tidal concentration decreased spontaneously. We also attempted to explain the difference in the average of the bracketing alveolar anesthetic concentration that allows and prevents the response to verbal command during recovery from anesthesia (MAC-Awake) between slow and fast alveolar washout by comparing the cerebral anesthetic concentrations with MAC-Awake determined by fast and slow washout. Slow washout was obtained by decreasing anesthetic concentrations in predetermined steps of 15 min, assuming equilibration between brain and alveolar partial pressures. Fast alveolar washout was obtained by discontinuation of the inhaled anesthetic, which had been maintained at 0.5 minimum alveolar anesthetic concentration (MAC) for at least 15 min. MAC-Awake values for sevoflurane and isoflurane obtained by slow washout were 0.34 +/- 0.05 and 0.31 +/- 0.05 (mean +/- SD), respectively, when MAC-Awake was expressed as a ratio to age-adjusted MAC. MAC-Awake values obtained by fast washout (0.22 +/- 0.07 MAC for sevoflurane, 0.22 +/- 0.05 MAC for isoflurane) were significantly smaller than those obtained by slow washout. Anesthetic concentrations in the brain at first eye opening calculated with end-tidal concentrations during fast alveolar washout (0.34 +/- 0.08 MAC for sevoflurane, 0.30 +/- 0.08 MAC for isoflurane) were nearly equal to MAC-Awake obtained by slow alveolar washout. The difference in MAC-Awake between fast and slow alveolar washout could be explained by arterial-to-cerebral and end-tidal-to-arterial anesthetic differences. PMID- 8214699 TI - Excitatory effects and electroencephalographic correlation of etomidate, thiopental, methohexital, and propofol. AB - Excitatory movements have been observed during induction of anesthesia with etomidate, thiopental, methohexital, and propofol. We studied the frequency of these excitatory effects and correlated movements with electroencephalographic (EEG) findings in 67 unpremedicated patients (mean age 66.1 yr, range 45-82 yr). Excitatory effects, including myoclonus, tremor, and dystonic posturing, occurred in 86.6% of patients receiving etomidate; 69.2% of the patient responses were myoclonic. Multiple spikes appeared on the EEG in 22.2% of the etomidate patients. The frequency of excitatory effects was 16.6% after thiopental, 12.5% after methohexital, and 5.5% after propofol. None of the patients receiving thiopental, methohexital, or propofol developed myoclonic or seizure activity. In most patients, the excitatory movements were coincident with the early slow phase of the EEG which corresponds to the beginning of deep anesthesia. We conclude that perhaps caution should be exercised when administering etomidate to patients with a history of seizures as the myoclonic activity is associated with seizure activity. The incidence of excitatory movements after administration of propofol is very low. PMID- 8214701 TI - Serum inorganic fluoride levels in mildly obese patients during and after sevoflurane anesthesia. AB - Serum inorganic fluoride levels in obese versus control patients were compared during and after sevoflurane anesthesia. Mean serum inorganic fluoride levels in the obese group increased more rapidly and were significantly higher than in the control group at each sampling time (P < 0.01). The area under the curve of fluoride concentration, versus time up to 24 h and 48 h in the obese patients, was significantly greater than that in the nonobese patients (P < 0.001). Peak serum fluoride level in the obese patients was 51.7 +/- 2.5 mumol/L and exceeded 50 mumol/L for nearly 2 h. Our study showed that serum fluoride concentrations between mildly obese and nonobese patients differed during and after sevoflurane anesthesia. PMID- 8214702 TI - Immediate responses of arterial blood pressure and heart rate to sudden inhalation of high concentrations of isoflurane in normotensive and hypertensive patients. AB - Inhalation of pungent volatile anesthetics elicits respiratory reflex responses. To clarify whether an upper airway irritation produced by pungent anesthetics can also induce circulatory reflex responses that are clinically significant, a sudden administration of 5% isoflurane by mask was performed during continuous measurement of arterial blood pressure (BP) and heart rate (HR) in eight normotensive and eight hypertensive patients anesthetized with thiamylal and paralyzed with vecuronium. The sudden administration of 5% isoflurane caused immediate increases in BP, HR, and rate pressure products (RPP) in both normotensive and hypertensive patients. The responses observed were more pronounced in hypertensive than in normotensive patients. The circulatory changes in hypertensive patients were sufficient to be clinically significant. Our findings suggest that sudden administration of a high concentration of pungent volatile anesthetics may be associated with transient hypertensive responses in hypertensive patients with coronary artery disease. PMID- 8214703 TI - Staurosporine, a protein kinase C inhibitor, decreases the general anesthetic requirement in Rana pipiens tadpoles. AB - Protein kinase C, the intracellular effector for the inositol phosphate-mediated signal transduction pathway, plays a key role in neurotransmission in the central nervous system. Although the in vitro activity of protein kinase C is inhibited by therapeutic concentrations of volatile anesthetics, the relation of this effect to in vivo obtundation has not been established. If obtundation by volatile anesthetics involves protein kinase C inhibition, then an inhibitor of this enzyme should decrease the anesthetic requirement. To test this hypothesis, we compared the EC50S of halothane and diethylether for loss of the righting reflex in Rana pipiens tadpoles pretreated with staurosporine and in untreated controls. Anesthetic concentrations were confirmed by gas chromatography and staurosporine concentrations by ultraviolet absorbance spectrophotometry. Results obtained in more than 1000 animals indicated that pretreatment with staurosporine concentrations in the nanomolar range significantly decreased the EC50 for both halothane (68% of control; P < 0.035) and diethylether (41% of control; P < 0.001). This finding implies that protein kinase C inhibition may play a role in general anesthetic-induced obtundation. PMID- 8214704 TI - A proposal to use confidence intervals for visual analog scale data for pain measurement to determine clinical significance. AB - Visual analog scales (VAS) ranging from 0 cm (no pain) to 10 cm (worst imaginable pain) are used widely for pain measurement, but various investigators have not treated these data consistently. Conventional statistical tests of such data, although evaluating the "statistical significance" may obscure the clinical value of a treatment. On the other hand, confidence intervals (CIs) can illuminate both statistical and clinical importance. CIs give a range of values based on the observed data which contain, with a specified probability, a true but unknown variable typifying a population. We reviewed 112 articles published recently in anesthesia journals for statistical reporting of VAS data. Of the 112 articles, only two used CIs to report mean pain scores and one used CIs to report differences in median pain scores between the study groups. Only two articles presented 95% CI for the mean pain scores graphically. Analgesic techniques that produce VAS values in the range of 0-3 have been reported to represent adequate analgesia. A graphical method using CIs is proposed that allows ready interpretation of VAS data. With this approach, one evaluates whether the 95% CI for the mean pain score in a group during a particular period lies entirely within the zone defined as "analgesic success" (0-3). Such an analysis allows a visual assessment of whether a particular technique would produce clinically important effects in the population at large. This approach seems to provide more information than the use of conventional hypothesis testing in the interpretation of VAS data for pain measurement. PMID- 8214705 TI - Adverse effects of stellate ganglion block on Raynaud's phenomenon associated with progressive systemic sclerosis. PMID- 8214706 TI - Loss of blood pressure monitoring during shunt positioning for carotid endarterectomy. PMID- 8214708 TI - Anesthetic management of children with moyamoya syndrome. PMID- 8214707 TI - Epidural anesthesia complicated by fluid collection within the spinal cord. PMID- 8214709 TI - Propofol sedation may disrupt interictal epilepiform activity from a seizure focus. PMID- 8214710 TI - Occult pheochromocytoma in association with hyperthyroidism presenting under general anesthesia. PMID- 8214711 TI - A hot mnemonic for the treatment of malignant hyperthermia. PMID- 8214712 TI - Combined interpleural analgesia/continuous brachial plexus block for breast surgery. A new solution for a problem? PMID- 8214713 TI - Univent tube: a simple method for avoiding a potentially disastrous complication. PMID- 8214714 TI - An intraoperative use of a laser pointer. PMID- 8214715 TI - Damage to laryngeal masks during sterilization. PMID- 8214716 TI - Rotating the epidural needle: a caution. PMID- 8214717 TI - Prevention of latex allergy. PMID- 8214718 TI - The best prophylaxis for succinylcholine myalgias: extension of a previous meta analysis. PMID- 8214719 TI - Preoxygenation in women: effect of posture. PMID- 8214720 TI - An alternative technique for locating the radial artery. PMID- 8214721 TI - Epidural meperidine provides surgical anesthesia for critically ill patients undergoing major surgery. PMID- 8214722 TI - A simpler method of administration of metered dose inhalers during general anesthesia via gas sampling port. PMID- 8214723 TI - A practical way of performing Allen's test to assess palmar collateral circulation. PMID- 8214724 TI - N omega-nitro-L-arginine methyl ester prevents cerebral hyperemia by inhaled anesthetics in dogs. AB - The mechanism by which halothane, isoflurane, and nitrous oxide increase cerebral blood flow (CBF) is unknown. We assessed the cerebrovascular effects of nitrous oxide (70%; n = 6), isoflurane (1 minimum alveolar anesthetic concentration: 1.4%; n = 6) or halothane (1 minimum alveolar anesthetic concentration: 0.8%; n = 6) before and after blockade of nitric oxide (NO) synthase with 40 mg/kg N omega nitro-L-arginine methyl ester (L-NAME) intravenously in dogs with baseline pentobarbital anesthesia. Baseline CBF (microspheres) was determined after 1 h of pentobarbital anesthesia. Cerebral perfusion pressure (CPP) was maintained during inhaled anesthetic or L-NAME by either hemorrhage or inflation of an intra-aortic balloon. Before L-NAME, halothane and isoflurane increased CBF (40 +/- 4 to 56 +/ 6 mL.min-1 x 100 g-1 and 43 +/- 6 to 78 +/- 12 mL.min-1 x 100 g-1, respectively) with no change in cerebral oxygen consumption (baseline: halothane, 2.6 +/- 0.2; isoflurane, 2.0 +/- 0.2 mL.min-1 x 100 g-1). On the contrary, nitrous oxide increased CBF similarly (40 +/- 6 to 57 +/- 8 mL.min-1 x 100 g-1), but increased cerebral oxygen consumption (2.2 +/- 0.3 to 3.0 +/- 0.3 mL.min-1 x 100 g-1). L NAME decreased blood flow in the neurohypophysis by 80% with no change in blood flow in other brain regions. After L-NAME, reexposure to nitrous oxide, halothane, or isoflurane resulted in no change in CBF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214725 TI - Effects of isoflurane, fentanyl, or thiopental anesthesia on regional cerebral blood flow and brain surface PO2 in the presence of a focal lesion in rabbits. AB - These studies were conducted to determine the effect of anesthetic drugs on tissue perfusion and O2 supply in the brain with focal cerebral edema. Using an open cranium preparation, we studied the effects of isoflurane (I; 1 minimum alveolar anesthetic concentration), of fentanyl (F; 0.5-1 microgram.kg-1 x min 1), or of thiopental (T; 32.5 mg.kg-1 x h-1) on regional cerebral blood flow (rCBF) and regional brain tissue PO2 in albino rabbits (n = 6 per group) with a focal brain lesion (cold injury). The doses of anesthetics were sufficient to suppress nociception. rCBF (H2 clearance) and tissue PO2 (multiwire surface electrode) were studied adjacent to and distant from the lesion. Cerebral hyperemia developed immediately after trauma in all groups, although the flow increase did not attain statistical significance. rCBF was subsequently reduced by about 25% in the vicinity of the lesion. Distant from the trauma, a continuing hyperemia (+30%) was later observed in animals with isoflurane, whereas rCBF was decreased then by 10%-20% in animals with fentanyl, or was unchanged with thiopental. Brain tissue PO2 was increased with isoflurane in areas distant from the lesion, but decreased with fentanyl. However, with thiopental, the PO2 level had already been lowered before trauma with a subsequent tendency toward normalization. The heterogeneity of the tissue PO2 in fentanyl anesthesia, as well as the increased frequency of hypoxic PO2 values with thiopental, might have resulted from microcirculatory disturbances. Thus, although isoflurane seemed to facilitate hyperemia with an increased O2 supply to the brain, fentanyl tended to induce the opposite response. Although these properties suggest the potential to manipulate perfusion and O2 supply in cerebral ischemia or hyperemia after head injury, the effects of such measures on intracranial pressure, neurologic status, and outcome have yet to be proven. PMID- 8214726 TI - Monitoring of intraoperative motor-evoked potentials under conditions of controlled neuromuscular blockade. AB - Motor-evoked potentials were recorded after electrical spinal cord stimulation in 19 patients undergoing neurosurgical or orthopedic procedures. Anesthesia was maintained with nitrous oxide, opioids, and inhaled anesthetics. Vecuronium was infused sufficient to eliminate 90% of twitch tension. The spinal cord was stimulated using either epidural or subarachnoid electrodes. Compound muscle action potentials were recorded from quadriceps and tibialis anterior muscles. Well-formed, stable motor-evoked potentials were recorded in all but one patient, in whom a preexisting myelopathy was felt to preclude recording. Intraoperative deterioration of motor-evoked potentials occurred in one patient who had a postoperative neurologic deficit. This study demonstrates the feasibility and utility of intraoperative motor tract monitoring using direct spinal cord stimulation. Controlled neuromuscular blockade permits recording of compound muscle action potentials while eliminating patient motor activity that could interfere with surgery. PMID- 8214727 TI - Epidural anesthesia for labor in an ambulatory patient. AB - The effectiveness of two epidural analgesic regimens on the ability to ambulate was compared in women in labor by a prospective, randomized, double-blind design. One group of patients received epidural fentanyl, a 75-micrograms bolus and an infusion of fentanyl 2.5 micrograms/mL at 15 mL/h (FENT, n = 53). A second group received ultra low-dose bupivacaine (0.04%), epinephrine (1.7 micrograms/mL), and fentanyl (1.7 micrograms/mL) (BEF, n = 77), a 15-mL bolus followed by an infusion at 15 mL/h. Adequate analgesia was rapidly obtained in 90.6% of patients in the FENT group and 92.2% of patients in the BEF group (P = 0.89). Seventy percent of patients in the FENT group ambulated versus 68% in the other group. The BEF mixture provided analgesia of longer duration (287 +/- 171 min versus 156 +/- 72 min, P = 0.0001). The number of patients delivering during administration of only their study drug (without needing higher doses of local anesthetics) was 52% for BEF and 21% for FENT (P = 0.0005). Hip flexion weakness precluding ambulation occurred in 17% (P = 0.002) of BEF patients and orthostatic hypotension in 9% (P = 0.08). Neither problem occurred in FENT patients. Neonatal outcome was similar in both groups. Approximately 70% of women receiving epidural analgesia with fentanyl or ultra low-dose bupivacaine, epinephrine, and fentanyl may ambulate safely during labor. PMID- 8214728 TI - Opioid antagonist adjuncts to epidural morphine for postcesarean analgesia: maternal outcomes. AB - This prospective, randomized, controlled investigation compared the effects of three prophylactic mu-opioid antagonists, epidural butorphanol (BU) 3 mg, epidural nalbuphine (NB) 10 mg, and oral naltrexone (NX) 6 mg, on postcesarean epidural morphine analgesia. After randomization, 102 term parturients underwent cesarean delivery with epidural anesthesia, 2% lidocaine and epinephrine 1:200,000. When the umbilical cord was clamped, each patient received one epidural solution (containing morphine 4 mg plus either saline or treatment drug), and one oral capsule (containing either placebo or treatment drug) in a double-blind manner. Maternal outcomes included pain and satisfaction [assessed with 100-mm visual analog scales (VAS)], and the incidence and severity of respiratory depression, somnolence, pruritus, nausea, and emesis. Through the first 12 h postpartum, the BU group achieved significantly greater analgesia than the morphine sulfate (control) (MS), NB, and NX groups, a significantly lower incidence of severe pruritus than the MS group, and significantly greater satisfaction than MS and NX groups. Epidural morphine and BU promoted better analgesia and satisfaction than any previously documented postcesarean regimen. PMID- 8214729 TI - Multiple effects of morphine on facial scratching in monkeys. AB - The medullary dorsal horn (MDH), the medullary homolog of the spinal dorsal horn, is a site where opioid-receptor agonists can act at opioid receptors to produce pronounced facial scratching, the behavioral correlate of pruritus. In the present study, after a 10-min baseline period, morphine (5.0 micrograms) was micro-injected into the MDH of monkeys. Behavior was videotaped and facial scratches were counted by two independent raters. Morphine greatly increased facial scratching behavior, which is consistent with previous findings where mu opioid receptor agonists microinjected into the MDH have been to induce dose dependent, naloxone-reversible facial scratching in monkeys. In the current research, intramuscular (IM) administration of the opioid-receptor antagonist, naloxone (0.5 mg/kg), reversed this MDH morphine-induced scratching. Additionally, IM morphine (1.0 mg/kg) produced a substantial reduction in facial scratching behavior. Scratching behavior continued at a high rate after injection of saline (0.1 mL/kg, IM). These findings support the hypothesis that morphine has both pruragenic and antipruragenic activity, depending on the site of action. PMID- 8214730 TI - Prolonged intrathecal fentanyl analgesia via 32-gauge catheters after thoracotomy. AB - We hypothesized that intrathecal fentanyl infusion would provide excellent analgesia, require lower doses than necessary for the epidural or intravenous route of administration, and reduce the incidence and/or severity of side effects. Accordingly, we studied 12 patients during 48 h after thoracotomy (three pneumonectomies, six lobectomies, and three multiple resections of metastases or pleural surgery). The mean dose of fentanyl infused intrathecally was 0.81 +/- 0.26 microgram.kg-1 x h-1, and plasma fentanyl concentrations ranged between 0.49 +/- 0.19 and 0.72 +/- 0.34 ng/ml. Four patients needed a supplementary bolus of intrathecal fentanyl. Pain scores decreased below 30/100 within 1 h when measured at rest but required 24 h to decrease to the same level during coughing. Pulmonary function tests returned to approximately 50% of preoperative values within 1 h of fentanyl infusion. Mean respiratory rates averaged 19 +/- 4, and no episode of apnea was detected. Pruritus, nausea, and headache occurred, respectively, in four, one, and zero patients. Excessive pressure in the infusion system occurred frequently, limiting fentanyl infusion in two patients. All catheters were removed intact; however, one broke outside of the patient's back. This study demonstrates that intrathecal fentanyl infusion can safely provide rapid and intense analgesia but that current 32-gauge intrathecal catheters are not well suited for prolonged postoperative use. PMID- 8214731 TI - Minimum effective combination dose of epidural morphine and fentanyl for posthysterectomy analgesia: a randomized, prospective, double-blind study. AB - Recent studies have produced conflicting results regarding whether the addition of epidural fentanyl improves postoperative analgesia from epidural morphine. Therefore, we prospectively determined the dose-response relationship and the minimum effective combination dose of epidural morphine and fentanyl (fentanyl given after morphine) for posthysterectomy analgesia. We studied 120 patients undergoing radical abdominal hysterectomy. All patients had epidural lidocaine 1.5% with epinephrine (1:200,000) for surgical anesthesia followed by light general anesthesia with endotracheal intubation. They were assigned randomly into six groups according to the combination of each narcotic dose: morphine 2 mg, morphine 2 mg/fentanyl 50 micrograms, morphine 2 mg/fentanyl 100 micrograms, morphine 4 mg, morphine 4 mg/fentanyl 50 micrograms, and morphine 4 mg/fentanyl 100 micrograms. Morphine and fentanyl were given epidurally in a double-blind manner approximately 60 and 15 min, respectively, before the completion of surgery. For 2 mg of morphine, the addition of 50 or 100 micrograms of fentanyl improved pain relief during the first 6 h postoperatively (P < 0.05), provided longer duration of analgesia (P < 0.05), and required less analgesic supplement (P < 0.05), but did not alter the incidence of side effects. For 4 mg of morphine, the same conclusion was drawn, except that vomiting occurred more frequently with addition of 100 micrograms of fentanyl (P < 0.05). Among fentanyl groups, there was no significant difference in pain scores, duration of analgesia, and analgesic requirements. Therefore, we conclude that epidural fentanyl given after morphine improves early postoperative analgesia from epidural morphine, and the minimum effective combination dose is morphine 2 mg/fentanyl 50 micrograms for posthysterectomy surgery analgesia. PMID- 8214732 TI - Effects of ephedrine on indocyanine green clearance during spinal anesthesia: evaluation by the finger piece method. AB - We measured indocyanine green (ICG) clearance in 20 patients scheduled for elective surgery during spinal anesthesia to determine whether ephedrine affects the hepatic circulation during spinal anesthesia. The clearance was measured by a new noninvasive finger piece method. We found that a decrease in arterial blood pressure secondary to spinal anesthesia significantly reduced ICG, whereas there were no significant changes in ICG clearance in the patients whose arterial blood pressures were maintained at preanesthetic levels by ephedrine. Other hemodynamic variables, heart rate, cardiac index, and stroke volume index, did not change significantly in either group. We conclude that hepatic blood flow is decreased by hypotension due to spinal anesthesia and can be attenuated by ephedrine administration. PMID- 8214733 TI - Establishing intravenous access: a study of local anesthetic efficacy. AB - We performed a double-blind, randomized, prospective study to determine the local anesthetic that provided the best analgesia for insertion of an 18-gauge intravenous (i.v.) catheter and to determine whether alkalinization of lidocaine decreases the pain of intradermal injection. There were 280 healthy adult patients assigned randomly to seven different groups: benzyl alcohol 0.9% in normal saline, 2-chloroprocaine 3%, lidocaine 1%, lidocaine 1% with preservative, alkalinized lidocaine 1% with preservative, normal saline, and a control group that received i.v. catheter placement without previous drug injection. A 10-cm visual analog pain scale (VAPS) was used to obtain pain scores after pre-i.v. drug injection and after iv catheter insertion. Benzyl alcohol in normal saline (0.61 +/- 0.11) and alkalinized lidocaine (0.69 +/- 0.10) had the lowest mean pain scores for drug injection and these were significantly different from other drugs (P < 0.05). Alkalinized lidocaine (0.7 +/- 0.18) had the lowest mean pain score for i.v. catheter insertion with nothing (no previous drug injected) (3.47 +/- 0.38) and normal saline (3.97 +/- 0.18) had the highest mean pain scores (P < 0.05). We conclude that alkalinized lidocaine decreased the pain associated with its injection. Alkalinized lidocaine was the best local anesthetic for i.v. catheter placement. Benzyl alcohol in normal saline was also effective. PMID- 8214734 TI - The effect of nitrous oxide on left ventricular pump performance and contractility in patients with coronary artery disease: effect of preoperative ejection fraction. AB - To elucidate the effects of nitrous oxide (N2O) on left ventricular (LV) pump performance and contractility, 28 patients undergoing coronary artery bypass graft surgery were studied, of whom 15 had depressed global LV function at preoperative catheterization. Transesophageal echocardiography and simultaneous hemodynamic measurements were used to assess LV preload, afterload, and systolic performance during inhalation of 100% oxygen (O2) and 60% N2O:40% O2. Systolic function indices were expressed as a percent of the predicted value for observed end-systolic stress to provide estimates of LV contractility. In the entire study population, N2O reduced pump performance (cardiac index 2.4 +/- 0.8 to 2.2 +/- 0.6 L.min-1 x m-2; P < 0.02). Heart rate and mean arterial pressure were reduced (67 +/- 13 to 64 +/- 13, P < 0.01, and 87 +/- 9 to 80 +/- 15, P < 0.005) as were left and right ventricular stroke work index. Preload, as measured by end diastolic stress, was unchanged but afterload, as measured by end-systolic stress, tended to decrease (88 +/- 31 to 78 +/- 28, P = 0.053). In the 13 patients with normal preoperative LV function, mean arterial pressure and LV stroke work index decreased significantly (91 +/- 8 to 84 +/- 14, P < 0.04, and 40 +/- 13 to 34 +/- 10, P < 0.04, respectively) and end-systolic stress tended to decrease (P = 0.054).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214735 TI - Reperfusion injury and exhaled hydrogen peroxide. AB - Reactive oxygen species have been implicated in the pathophysiology of lung injury associated with the sequence of ischemia-reperfusion. To study this, we measured the exhaled breath hydrogen peroxide concentration [H2O2] in human and canine models of reperfusion lung injury. Our models were patients subjected to cardiopulmonary bypass (CPB) (Group 1), patients undergoing pulmonary thromboendarterectomy (Group 2), canine single lung transplant (Group 3), and patients subjected to peripheral ischemia resulting from aortic cross-clamping or tourniquet application (Group 4). In addition, we studied two groups with severe lung injury as positive controls. These consisted of hydrochloric acid (HCl) induced canine lung injury (Group 5) and patients with adult respiratory distress syndrome (Group 6). The exhaled H2O2 was collected by using a -2 degrees C glass coil and assayed by a spectrophotometric method. In Group 1 samples were collected before and immediately after CPB. Group 2 samples were obtained before CPB, immediately after CPB, 3 h later, and daily until extubation. Samples in Group 3 were collected before lung transplant, and hourly for 3 h beginning immediately afterward. Group 4 samples were collected at the onset of reperfusion. Samples from Group 5 were collected before HCl and after HCl injury, at 0.5-1.5 and 2-3 h. Group 6 samples were collected when criteria for adult respiratory distress syndrome were met. Groups 1, 3, and 4 exhibited no significant increases in exhaled [H2O2] compared to control values. Group 2 had significantly increased [H2O2] (5.59 +/- 3.07 x 10(-7) mol/L, P = 0.028) on postoperative Day 2, but there was no correlation of [H2O2] with physiologic indicators of lung injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214736 TI - Reliability of a new generation transesophageal Doppler device for cardiac output monitoring. AB - A new generation continuous-wave transesophageal Doppler (TED) device for cardiac output (CO) monitoring (Accucom 2, Datascope), which displays aortic blood flow velocity in real time, was evaluated by 140 simultaneous comparisons with thermodilution (TD) in 16 patients early after coronary artery bypass surgery. The aim was to determine whether this technologic advancement improves the accuracy of COTED assessment. Absolute COTED values showed a considerable scatter as compared to COTD [COTED = 1.77 + 0.75.COTD (L/min), r = 0.52]. The bias, i.e., the mean of individual CO differences (COTD-COTED) was -0.37 +/- 1.70 L/min (SD). In contrast, relative CO changes (delta CO, % of preceding value) showed a satisfactory agreement between TED and TD [delta COTED = 1.04 + 0.91.delta COTD (%), r = 0.84, n = 124], the bias (delta COTD-delta COTED) being -0.66 +/- 9.72%. In 8 of 124 situations (6.45%), however, significant COTED changes opposite in direction to that of significant COTD changes occurred. This frequency was significantly greater (P < 0.01) than the ideal frequency of 0%. The agreement between delta COTD and delta COTED improved (P < 0.05) when the aortic diameter changes induced by changes in mean arterial pressure were considered [delta COTEDMAPC = 1.10 + 0.95.delta COTD (%), r = 0.87, n = 124]. Compared with previous results, the reliability of the second generation device to monitor relative CO changes was considerably improved. Provided that the aortic blood flow velocity signal was stable and free from any disturbances, the second generation TED device may be regarded acceptable for CO trend monitoring in sedated, paralyzed patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214737 TI - Absence of agonist effects of high-dose flumazenil on ventilation and psychometric performance in human volunteers. AB - Flumazenil, a specific benzodiazepine antagonist, reverses sedative and respiratory depressant effects of benzodiazepines. We determined whether a large dose of flumazenil, injected alone, induces respiratory depression or alteration of psychomotor performance. After informed consent, eight healthy volunteers participated at three different sessions: 1) flumazenil (0.1 mg/kg) (a dose 7-15 times the clinically recommended dose) injected intravenously over a 5-min period, followed by placebo (NaCl 0.9%); 2) flumazenil at the same dose and injection rate as in Session 1, followed by midazolam (0.1 mg/kg) injected over 5 min; and 3) placebo followed by midazolam at the same dose as above and administered over 5 min. All drug combinations were administered in a randomized and double-blind manner. Tidal volume, respiratory frequency, minute ventilation, and mean inspiratory flow were continuously measured from 15 min before until 120 min after drug injection by noninvasive on-line data acquisition methods. Psychometric performance was evaluated 15 min before the first drug and 15 min after administration of the second drug. During the placebo-midazolam session, tidal volume (-40%), minute ventilation (-25%), and inspiratory flow (-25%) were significantly (P < 0.01) decreased compared both with baseline and with the other two sessions, and psychometric performance was significantly (P < 0.01) altered; in contrast, there was no significant change in any of the measured respiratory or psychometric variables during the flumazenil-placebo or flumazenil-midazolam sessions. We conclude that flumazenil, administered at about 10 times the clinically recommended dose, has no agonist effects on resting ventilation or psychomotor performance in normal subjects. PMID- 8214738 TI - Pharmacokinetics and technique of endotracheal and deep endobronchial lidocaine administration. AB - To determine absorption characteristics of endotracheal lidocaine, we administered lidocaine to hemodynamically stable patients by different techniques. Blood samples were taken for measurement of lidocaine plasma concentrations (fluorescence polarization immunoassay), and pharmacokinetics were calculated by regression analysis. Plasma concentrations at 1.5 and 2 min after drug administration were higher (P < 0.05) after instillation into the endotracheal tube (1.40 +/- 0.19 and 1.26 +/- 0.14 microgram/mL) than after deep endobronchial administration (1.00 +/- 0.08 and 0.83 +/- 0.05 microgram/mL). A biphasic absorption with a division of the area under the curve (AUCtot) into two parts (AUC1 and AUC2) could be assumed. After tube instillation, the AUC1/AUCtot ratio (2.6%) was higher (P < 0.05) than after deep endobronchial instillation (1.1%). To achieve high plasma concentrations within a short time, AUC1, representing a nearly instantaneous absorption, seems to be more important than AUC2, representing a higher but delayed absorption (depot effect). Because deep endobronchial lidocaine administration accentuated the late absorption, presumably by preventing drug distribution to the whole lung, this technique was detrimental to obtaining high plasma concentrations within a short period of time. PMID- 8214739 TI - Comparison of three techniques to inflate the bronchial cuff of left polyvinylchloride double-lumen tubes. AB - Correct inflation of the cuff of any breathing tube is important; overinflation can damage the mucosa of the tracheobronchial tree and underinflation will cause a leak. Three different techniques to determine cuff seal/leak during inflation of the bronchial cuff of left double-lumen endobronchial tubes (DLT) were each evaluated in 10 patients. DLT size was chosen from a formula based on the patient's height and sex. In the first technique, designated the positive pressure technique of bronchial cuff inflation (PPT), the bronchial side of the DLT is pressurized during connection of the tracheal side to a beaker of water. Air bubbles will appear in the beaker in the absence of bronchial seal. The second technique, designated the CO2 analysis technique of bronchial cuff inflation (CAT), is based on analysis of CO2 content of gas sampled from the tracheal side of the DLT during ventilation of its bronchial side. When the bronchus is sealed, the normal CO2 waveform changes to a flat line. In the third technique, designated the negative pressure technique of bronchial cuff inflation (NPT), suction is applied to the tracheal side of the DLT. The absence of bronchial seal will result in collapse of the reservoir bag within a breathing system connected to the bronchial side of the tube. The bronchial sealing volumes were 1.1 +/- 0.9 mL, 0.9 +/- 0.7 mL, and 0.3 +/- 0.4 mL (mean +/- SD) when measured with the PPT, CAT, and NPT, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214740 TI - Leg warming minimizes core hypothermia during abdominal surgery. AB - The efficacy of leg skin warming in preventing hypothermia and shivering was evaluated in two separate prospective, randomized trials in patients undergoing abdominal surgery. In the first trial, 22 patients were randomized to receive no hypothermia prevention (control group) or active warming with an electric warming blanket (electric blanket group). In the second trial 33 patients were randomized to receive no hypothermia prevention (control group) or forced-air warming (Bair Hugger group) or forced-air warming with insulation of the air blanket from the environment (insulated Bair Hugger group). The core and skin temperatures were measured and changes in body heat content calculated. In the first trial, core temperature was 34.6 +/- 0.3 degrees C at the end of surgery in the control group vs 36.4 +/- 0.1 degrees C in the electric warming blanket group (P < 0.001). Shivering occurred in nine control patients and in one warmed patient (P < 0.05). In the second trial, core temperature was 35.1 +/- 0.2 degrees C at the end of surgery in the control group, 36.3 +/- 0.1 degrees C in the Bair Hugger group (P < 0.01) and 37.1 +/- 0.1 degrees C in the insulated Bair Hugger group (P < 0.01 versus control; P < 0.05 versus Bair Hugger). Shivering occurred in one patient of each warmed group and in seven of the control group (P < 0.05). Skin-surface warming limited to the legs provides sufficient heat (ranging 34 to 43 watts) to counterbalance heat losses during abdominal surgery. PMID- 8214741 TI - Another call for patience instead of patients. Developing novel therapies for chronic pain. PMID- 8214742 TI - ASA Award. Kai Rehder. PMID- 8214743 TI - Subarachnoid adrenal medullary transplants for terminal cancer pain. A report of preliminary studies. AB - BACKGROUND: The prolonged use of opioids to treat intractable pain with currently available therapeutic modalities is often unsatisfactory, usually because of tolerance or complications. Extensive studies carried out in the authors' laboratories have indicated that the transplantation of adrenal medullary tissue into the spinal subarachnoid space can significantly reduce pain in animal pain models, most likely via release of opioid peptides and catecholamines. The current study was undertaken to assess the feasibility and efficacy of subarachnoid adrenal medullary transplantation in alleviating terminal cancer pain in humans. METHODS: Two milliliters of human adrenal medullary tissue were prepared in the laboratory and then transplanted via lumbar puncture into the subarachnoid space in five patients suffering from terminal cancer pain. Pain scores (VAS), functional activity, and opioid intake were assessed and recorded before and after the transplantation procedure. In addition, CSF samples were collected before and (when possible) at fixed intervals after transplantation for biochemical and cytologic analysis. RESULTS: Four of the five patients demonstrated progressive decreases in pain scores after the transplant procedure, with concomitant reductions in opioid intake. Three of these four patients remained pain free, two for over 10 months, while the other had a recurrence of her pain after surgery for spinal cord compression secondary to metastases 10 weeks after transplant. The fifth patient had no pain reduction by 1 month after the procedure, and refused further followup. After the transplants, spinal CSF samples revealed increased concentrations of met-enkephalin in three of the five patients, and increased concentrations of catecholamines in the four patients in whom they were determined. CONCLUSIONS: The results obtained in this study indicate that subarachnoid adrenal medullary transplantation may provide a unique and effective approach to the management of intractable chronic pain in humans. PMID- 8214744 TI - Diaphragmatic shortening after thoracic surgery in humans. Effects of mechanical ventilation and thoracic epidural anesthesia. AB - BACKGROUND: Diaphragmatic function is believed to be inhibited after thoracic surgery and may be improved by thoracic epidural anesthesia. METHODS: Diaphragmatic function after a thoracotomy was monitored by implanting one pair of sonomicrometry crystals and two electromyogram (EMG) electrodes on the costal diaphragm of six patients undergoing an elective pulmonary resection. Crystals and EMG electrodes remained in place for 12-24 h. RESULTS: During mechanical ventilation, costal diaphragmatic length (as a percent of rest length; %LFRC) decreased passively as tidal volume (VT) increased (%LFRC = 2.81 + 1.12 x 10(-2) VT (ml), r = 0.99). During spontaneous ventilation, the costal shortening (2.1 +/ 2.3 %LFRC) was less than during mechanical ventilation (7.9 +/- 3.0 %LFRC, P < 0.05) at the same VT. Comparing spontaneous ventilation before and 30 min after thoracic epidural anesthesia, there were increases of VT (390 +/- 78 to 555 +/- 75 ml), vital capacity (1.37 +/- 0.16 to 1.68 +/- 0.21 l), and esophageal (-8.5 +/- 1.5 to -10.6 +/- 1.7 cmH2O), gastric (-0.7 +/- 0.8 to +0.8 +/- 0.8 cmH2O), and transdiaphragmatic (7.7 +/- 1.5 to 11.5 +/- 1.9 cmH2O) pressures, but diaphragmatic EMG and shortening fraction remained constant. In three of six patients, epidural anesthesia produced paradoxical segment lengthening upon inspiration. CONCLUSIONS: Thoracotomy and pulmonary resection produce a marked reduction of active diaphragmatic shortening, which is not reversed by thoracic epidural anesthesia despite improvement of other indices of respiratory function. PMID- 8214745 TI - The effect of tirilazad mesylate (U74006F) on cerebral oxygen consumption, and reactivity of cerebral blood flow to carbon dioxide in healthy volunteers. AB - BACKGROUND: The 21-aminosteroids are a series of compounds designed to inhibit lipid peroxidation in the cell, and, as such, may have cerebral protective effects. The current study was performed to evaluate the effect of a 21 aminosteroid, tirilazad mesylate (U74006F), on cerebral blood flow, metabolism, and carbon dioxide reactivity. METHODS: Using a double-blind study design, eight volunteers received tirilazad mesylate, and eight others received only vehicle. The cerebral blood flow was measured by single photon emission computerized tomography using 133Xe inhalation in the resting condition at the beginning of the study and after infusion of tirilazad mesylate (1.5 mg/kg) or vehicle. Cerebral oxygen metabolism was calculated from the cerebral blood flow and the measured cerebral arteriovenous oxygen content difference. After both of the above cerebral blood flow measurements, arterial carbon dioxide tension was decreased by voluntary hyperventilation, and, later, increased by breathing an air/carbon dioxide mixture. The relative changes in cerebral blood flow induced by the PaCO2 variations were estimated from the changes in the arteriovenous oxygen content difference. RESULTS: Blood pressure, pulse rate, and PaCO2 were similar before and after the infusion of tirilazad mesylate in both groups, and there was no difference between the groups. The cerebral blood flow and oxygen metabolism did not change after the tirilazad mesylate infusion. The slope of the regression line of relative change of estimated cerebral blood flow and PaCO2 (regression coefficients in both groups, > 0.90) was unchanged after infusion. CONCLUSIONS: Tirilazad mesylate has no effect on cerebral blood flow, cerebral oxygen metabolism, or reactivity of cerebral blood flow to carbon dioxide in healthy volunteers. PMID- 8214746 TI - Epidural versus intravenous fentanyl for reducing hormonal, metabolic, and physiologic responses after thoracotomy. AB - BACKGROUND: Previous attempts to prevent all the unwanted postoperative responses to major surgery with an epidural hydrophilic opioid, morphine, have not succeeded. The authors' hypothesis was that the lipophilic opioid fentanyl, infused epidurally close to the spinal-cord opioid receptors corresponding to the dermatome of the surgical incision, gives equal pain relief but attenuates postoperative hormonal and metabolic responses more effectively than does systemic fentanyl. METHODS: Forty patients were randomly assigned to receive either fentanyl epidurally and saline intravenously, or fentanyl intravenously and saline epidurally, in a double-blind fashion for the first 20 h after thoracotomy. For each patient, the fentanyl infusion was titrated to the rate required for pain relief (pain score < 3, maximum 10). Postoperative changes in blood pressure, heart rate, rectal temperature, and blood concentrations of adrenocorticotrophic hormone, beta-endorphin immunoreactivity, cortisol, growth hormone, prolactin, glucose, and leukocytes were assessed. RESULTS: Patients reported similar median pain scores, but the epidural group required about 40% less fentanyl than the intravenous group. Four hours postoperatively, the beta endorphin immunoreactivity concentrations were less in the epidural than in the intravenous group. Plasma cortisol increased in a similar manner in both groups within 4 h of surgery, but the increase persisted to the next morning only in patients receiving intravenous fentanyl. Adrenocorticotropin, growth hormone, and prolactin responses were similar in both groups. The postoperative hyperglycemic response, leukocytosis, and blood pressure were greater, and mean rectal temperature was lower, in the intravenous than in the epidural fentanyl group. CONCLUSIONS: The authors' results indicate that some aspects of the hormonal response to surgery are blocked more completely with epidural than with intravenous fentanyl. Adequate pain relief with epidural fentanyl, with a smaller mean dose, led to a smaller increase of some hormonal, metabolic, and physiologic responses after thoracotomy than in association with the adequate pain relief provided by intravenous fentanyl. PMID- 8214747 TI - Absence of nonshivering thermogenesis in anesthetized adult humans. AB - BACKGROUND: Typically, core temperature rapidly decreases after induction of anesthesia, but reaches a stable plateau after several hours. This plateau typically occurs in conjunction with the onset of thermoregulatory vasoconstriction. Decreased heat loss, caused by vasoconstriction, may not be sufficient to establish thermal steady state without a concomitant increase in heat production. Accordingly, the authors tested the hypothesis that nonshivering thermogenesis contributes to thermal steady state during anesthesia. Rewarming from hypothermia is often associated with an afterdrop (a further reduction in core temperature, despite cutaneous warming). Because total body heat content increases during cutaneous warming, heat storage during afterdrop must reflect increased temperature and heat content of the peripheral tissue mass. Thermal balance was measured during rewarming to estimate the thermal capacity of the peripheral tissues. METHODS: Five volunteers were anesthetized with isoflurane and paralyzed with vecuronium. Oxygen consumption was measured during cooling to a core temperature at least 1 degree C less than that which triggered vasoconstriction. Volunteers were subsequently rewarmed using a circulating-water blanket and forced-air warmer. Oxygen consumption and cutaneous heat flux were measured to assess thermal balance and peripheral tissue heat storage during rewarming. RESULTS: The core temperature threshold for vasoconstriction was 35.2 +/- 0.8 degrees C. Oxygen consumption decreased 9 +/- 5%/degrees C during active cooling before vasoconstriction and 9 +/- 3%/degrees C after vasoconstriction. After the start of rewarming, core temperature continued to decrease for an additional 32 +/- 8 min. The magnitude of this afterdrop was 0.6 +/- 0.1 degree C. Peripheral tissue heat storage measured from the start of rewarming until the first net increase in core temperature was 144 +/- 60 kcal, which approximately equals 2 h of resting metabolic heat production. CONCLUSIONS: The authors concluded that nonshivering thermogenesis is not an important thermoregulatory response in adults anesthetized with isoflurane. Afterdrop and delayed core temperature recovery during rewarming reflect the large heat storage capacity of peripheral tissues. PMID- 8214748 TI - Effects of sevoflurane on cerebral circulation and metabolism in patients with ischemic cerebrovascular disease. AB - BACKGROUND: Sevoflurane is a newly developed volatile anesthetic that has a low blood-gas partition coefficient. The effects of sevoflurane on the cerebral circulation or metabolism in humans have not been studied. The authors examined the cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) during sevoflurane anesthesia. The carbon dioxide response and autoregulation of cerebral circulation were also examined. METHODS: Ten patients with ischemic cerebrovascular disease undergoing extra-intracranial artery anastomosis were studied. Cerebral blood flow and CMRO2 were determined by the Kety-Schmidt method using argon. These procedures were performed during the inhalation of 33% N2O, 33% argon, and oxygen with 1.5% sevoflurane (0.88 minimum alveolar concentration). To examine the relationship of CBF to a change in PaCO2, CBF was measured repeatedly at steady state PaCO2, of 40, 35, and 45 mmHg. Furthermore, CBF was measured before and after an increase in mean arterial pressure (MAP) caused by intravenous infusion of methoxamine to determine the relationship between CBF and MAP. RESULTS: Cerebral blood flow and CMRO2 were 28 +/- 4 ml x 100 g-1 x min-1 and 1.34 +/- 0.23 ml x 100 g-1 x min-1, respectively. Cerebral blood flow was found to vary directly with PaCO2 alteration. The slope of the regression line between PaCO2 and CBF was 1.29 ml x 100 g-1 x min-1 x mmHg-1. On the other hand, CBF was constant throughout the elevation of MAP with vasopressor. CONCLUSIONS: Both carbon dioxide response and cerebral autoregulation were well maintained under 0.88 MAC sevoflurane anesthesia in patients with ischemic cerebrovascular disease. PMID- 8214749 TI - Minimum alveolar concentration of desflurane in patients older than 65 yr. AB - BACKGROUND: The minimum alveolar concentration (MAC) of desflurane/oxygen is 7.25% in the 18-30-yr age group, and 6.0% in the 31-65-yr age group. The addition of 60% N2O reduces MAC to 4.0 and 2.83%, respectively. Because MAC of other inhaled anesthetics is less than that for younger adults, we determined MAC of desflurane in adults aged 65 yr and older. METHODS: Thirty-nine patients, 21 of whom received 60% N2O/O2/desflurane, and 18 of whom received desflurane/oxygen, scheduled for surgery, were enrolled. They received no premedication, intravenous induction agent, opioid, or neuromuscular blocking agent for intubation. After 10 min or more at a steady end-tidal desflurane concentration, the incision was made. In both groups, six crossover pairs of patients responses (movement-no movement) provided a mean end-tidal concentration. Minimum alveolar concentration was defined as the average of the six crossover midpoints in each subgroup. RESULTS: MAC was 5.17 +/ 0.6% (mean +/- SD) in the desflurane/oxygen group. It was 1.67 +/- 0.4% in the desflurane/nitrous oxide/oxygen group. CONCLUSIONS: In the geriatric patient, MAC of desflurane, with or without nitrous oxide, is less than that reported in patients aged 18-65 yr. This is in agreement with results with all other inhalation agents. PMID- 8214750 TI - Transcutaneous cardiac pacing during thoracic surgery. Feasibility and hemodynamic evaluation by transesophageal echocardiography. AB - BACKGROUND: Occasionally, emergency perioperative pacing is necessary. Transcutaneous cardiac pacing is noninvasive, safe, and readily available. Its feasibility and hemodynamic effects during thoracic surgery and one-lung ventilation have not been established. METHODS: Twenty anesthetized patients (aged 25-70 yr) without cardiac disease undergoing elective pulmonary resection (right n = 10, left n = 10) were studied in normal sinus rhythm and during transcutaneous cardiac pacing. Patients were paced in supine and lateral decubitus positions (with closed and opened chest) at the minimal current necessary to produce ventricular capture. Invasive arterial monitoring permitted calculation of mean arterial pressure, and transesophageal echocardiography was used to assess atrial and ventricular wall motion and the evaluation of transmitral flow. Twelve patients underwent Doppler analysis of pulmonary venous flow. RESULTS: Pacing was achieved in all patients, with a mean threshold of 86.9 +/- 20.6 mA for the right thoracotomy group, and 106.7 +/- 16.2 mA for the left thoracotomy group. The mean paced heart rates for the right and left thoracotomy groups were 101.6 +/- 18.2 and 105.4 +/- 11.5 beats/min, respectively. During pacing, all patients sustained reversible transient decrements in mean arterial pressure (9-19%) from baseline, the loss of AV synchrony, and the development of paradoxical ventricular septal wall motion. No patient had significant mitral regurgitation during sinus or paced rhythms. Decreased systolic pulmonary venous flow velocity and abnormal systolic flow reversal were seen during pacing in 11 of the 12 patients studied. CONCLUSIONS: Transcutaneous cardiac pacing is effective in patients undergoing thoracotomy and one-lung ventilation. Its use in patients in normal sinus rhythm induces reversible decrements in mean arterial pressure because of the effects of altered atrioventricular association, ventricular wall motion, and pulmonary venous return. PMID- 8214751 TI - Does nitrous oxide antagonize isoflurane-induced suppression of learning? AB - BACKGROUND: A greater MAC fraction of nitrous oxide than isoflurane is required to prevent response to verbal commands and suppress the capacity to learn. Speculating that this difference between these agents may be caused by nitrous oxide's capacity to increase sympathetic activity, we tested the hypothesis that nitrous oxide may antagonize the suppression of learning found with isoflurane. METHODS: We administered a combination of isoflurane and nitrous oxide at three subanesthetic test concentrations (0.43, 0.56, and 0.68 MAC) to 24 healthy male volunteers. Assuming additivity of the anesthetics, the first test concentration was selected to suppress learning of new information by 50% (ED50 for suppression of learning); the second concentration, to suppress the ability to respond appropriately to verbal command by 50% (MAC-awake); and the third, to provide 1.4 times MAC-awake. Three tests of learning were applied. At each test concentration, we provided 7 answers to "trivial pursuit"-type questions, resulting in a set of 21 answered questions for each volunteer; an additional 7 unanswered questions served as controls. At the highest test concentration, each volunteer also heard two examples from each of two categories (4 words) repeated 30 times (the category-example task), and a message instructing them to touch either their nose or their ear during a specified interval in the postanesthetic interview (the behavior task). RESULTS: The MAC-awake value for the combination of isoflurane and nitrous oxide was 118 +/- 4% of the expected value (i.e., the two anesthetics were antagonistic for this effect). Consistent with antagonism, the anesthetic concentration predicted to suppress learning by 50% permitted significantly more learning, and the ED50 was 105 +/- 2% of that predicted. Neither the category task nor the behavior task demonstrated evidence of learning at 1.4 times MAC-awake. CONCLUSIONS: Our results are consistent with an antagonism between nitrous oxide and isoflurane; however, the degree of antagonism is small. PMID- 8214752 TI - Disposition and respiratory effects of intrathecal morphine in children. AB - BACKGROUND: The extent and duration of respiratory depression after opioid administration are poorly defined in infants and children. METHODS: The disposition and respiratory effects of intrathecal morphine were studied in ten patients (ages 4 months-15 yr) after repair of craniofacial defects. Morphine, 0.02 mg/kg, was administered intrathecally before the end of surgery. Postoperatively, we determined the minute ventilation (VE) in response to increasing partial pressure of end-tidal carbon dioxide (PETCO2) during carbon dioxide rebreathing. The slope (VE/PETCO2) and intercept (VE at PETCO2 60 mmHg, VE 60) of the carbon dioxide response curve were calculated at 6, 12, and 18 h after morphine administration. Cerebrospinal fluid (CSF) and blood were analyzed for morphine concentration by radioimmunoassay. RESULTS: Mean VE/PETCO2 decreased from a preoperative value of 35.1 +/- 3.7 to 16.3 +/- 2.8 ml.kg-1 x min-1 x mmHg 1 at 6 h after morphine, and remained depressed to 23.4 +/- 2.9 and 23.5 +/- 3.3 ml.kg-1 x min-1 x mmHg-1 at 12 h and 18 h, respectively, compared to preoperatively). The infants' (n = 3) VE/PETCO2 at 6 h were 21, 4, and 27 ml.kg-1 x min-1 x mmHg-1. Mean VE 60 decreased from 874 +/- 125 to 276 +/- 32 ml x kg-1 x min-1 at 6 h, but then recovered at 12 and 18 h to 491 +/- 68 and 567 +/- 82 ml.kg-1 x min-1, respectively. The infants' VE 60 at 6 h were 350, 142, and 245 ml.kg-1 x min-1. Mean CSF morphine concentration was 2,860 +/- 540 ng/ml at 6 h, and decreased to 640 +/- 220 and 220 +/- 150 ng/ml at 12 and 18 h, respectively. CONCLUSIONS: Intrathecal morphine, 0.02 mg/kg, depressed the ventilatory response to carbon dioxide for up to 18 h concomitant with increased CSF morphine concentrations. Infants (4-12 months of age) did not exhibit greater ventilatory depression than did children (2-15 yr of age). PMID- 8214753 TI - Dose-response relationships for edrophonium and neostigmine antagonism of rocuronium bromide (ORG 9426)-induced neuromuscular blockade. AB - BACKGROUND: Rocuronium bromide (ORG 9426) is a new nondepolarizing muscle relaxant with a rapid onset but an intermediate duration of action. The dose response relationships for neostigmine and edrophonium were studied during antagonism of neuromuscular block induced by rocuronium bromide. METHODS: Sixty four ASA physical status 1 or 2 adults were given 0.6 mg/kg rocuronium bromide during thiopental-fentanyl-nitrous oxide-isoflurane anesthesia. Train-of-four (TOF) stimulation was applied to the ulnar nerve every 10 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg/kg) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg/kg) was administered by random allocation. Neuromuscular function in another eight subjects was allowed to recover spontaneously. Assisted recovery was defined as actual recovery minus mean spontaneous recovery in patients who were not given antagonists. RESULTS: The dose-response curves for neostigmine- and edrophonium-assisted antagonism of rocuronium bromide neuromuscular blockade for the single twitch and TOF ratio were not parallel. The doses of neostigmine required to achieve 50% and 80% recovery (ED50 and ED80, respectively) of the first twitch after 10 min were 0.017 (0.001) and 0.033 (0.001) mg/kg (mean (standard error of estimate for the mean)), respectively. Corresponding ED50 and ED80 values for edrophonium were 0.161 (0.001) and 0.690 (0.001) mg/kg, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 9.5 (0.56) and 21 (0.67) for first twitch ED50 and ED80 height, respectively. The calculated doses producing ED50 of the TOF ratio at 10 min were 0.017 (0.001) and 0.469 (0.001) mg/kg for neostigmine and edrophonium, respectively. These values corresponded to a potency ratio of 27.5 (1.66). CONCLUSIONS: Under the conditions described in this study, if reversal was attempted at 10% first twitch recovery, edrophonium was less capable than neostigmine of reversing fade (potency ratio of 19.2 and 27.5 at 5 and 10 min, respectively) than first twitch (potency ratio of 6.7 and 9.5 at 5 and 10 min, respectively) during antagonism of rocuronium bromide-induced blockade. Edrophonium was found to be less effective than neostigmine at reversing rocuronium bromide-induced TOF fade. PMID- 8214754 TI - Potentiation of antinociceptive effects of morphine by calcium-channel blockers at the level of the spinal cord. AB - BACKGROUND: Opioids inhibit voltage-dependent calcium-channel conductance, which is essential for the nervous system to be able to signal a painful event. Accordingly, interference with calcium-channel conductance may enhance opioid analgesia. The current study was designed to investigate the effects of calcium channel blocking drugs on the antinociception of morphine at the level of the spinal cord. METHODS: Rats were chronically implanted with catheters in the lumbar intrathecal space. Tail-flick test was used to assess thermal nociception. Intrathecally administered drugs were morphine, calcium-channel blockers (verapamil, diltiazem, and nicardipine), or a combination of morphine and calcium channel blocker. RESULTS: Intrathecal administration of morphine produced a significant dose-dependent antinociception in the tail-flick test. In contrast, intrathecal administration of calcium-channel blockers, verapamil, diltiazem, and nicardipine, did not show any antinociception at the employed doses. However, when intrathecally administered calcium-channel blockers, verapamil (50 micrograms), diltiazem (100 micrograms), or nicardipine (20 micrograms), were combined with ineffective (0.25, 0.5, 1, or 2 micrograms) or moderately effective (5 micrograms) doses of intrathecally administered morphine, significant antinociception was produced. These interactions were synergistic. There were no significant changes in MAP or HR after the intrathecal administration of 200 micrograms verapamil or 2 micrograms morphine combined with 50 micrograms verapamil. CONCLUSIONS: The authors interpreted these results to indicate that calcium-channel blocking drugs synergistically potentiate the analgesic effects of morphine at the level of the spinal cord. Before these results can be translated into clinical use, however, adequate toxicity studies must be conducted to examine the effect of the perispinal administration of calcium channel blocking drugs on spinal cord function. PMID- 8214755 TI - Amrinone enhances myocardial contractility and improves left ventricular diastolic function in conscious and anesthetized chronically instrumented dogs. AB - BACKGROUND: Volatile anesthetics depress left ventricular mechanical performance in vivo by altering intracellular calcium regulation. Although amrinone has been shown to reverse the negative inotropic effects of volatile anesthetics, the actions of amrinone on anesthetic-induced diastolic dysfunction are unknown. This investigation examined and compared the direct effects of amrinone on left ventricular systolic and diastolic function in conscious and anesthetized dogs. METHODS: Experiments were conducted in the presence of pharmacologic blockade of the autonomic nervous system, because autonomic activity may influence the hemodynamic actions of volatile anesthetics and amrinone in vivo. Three groups, comprising a total of 27 experiments, were conducted using 9 dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dt, subendocardial segment length, diastolic coronary blood flow velocity, and cardiac output. Myocardial contractility was evaluated using the preload recruitable stroke work relationship slope (Mw). Diastolic function was characterized by a time constant of isovolumic relaxation (tau), a regional chamber stiffness constant (KT), and maximum segment lengthening velocity during rapid ventricular filling (dL/dtmax). On three separate days, an amrinone bolus of 1 mg/kg, followed by an infusion at 10, 20, 40, or 80 micrograms.kg-1.min-1, was administered. Hemodynamics and ventricular pressure-segment length loops and waveforms were recorded after a 15-min equilibration at each dose in the conscious state or during isoflurane or halothane anesthesia (1.25 MAC). RESULTS: In conscious dogs, amrinone significantly increased myocardial contractility in a dose-dependent manner (Mw of 65 +/- 8 to 108 +/- 10 mmHg at the high dose). Amrinone also shortened isovolumic relaxation (tau of 32.7 +/- 2.1 to 24.8 +/- 0.9 ms at the high dose) and enhanced rapid ventricular filling (dL/dtmax of 34.8 +/- 1.2 to 45.1 +/- 2.3 mm/s at the high dose) in a dose-related fashion. In addition, amrinone reduced regional chamber stiffness (Kp of 0.49 +/- 0.09 to 0.31 +/- 0.08 mm/s at the high dose) in conscious dogs. Amrinone also enhanced left ventricular systolic (increase in Mw) and diastolic function (decreases in tau and Kp and increases in dL/dtmax) when this drug was administered to dogs anesthetized with isoflurane or halothane. CONCLUSIONS: Amrinone produced positive inotropic and lusitropic effects in both conscious and anesthetized dogs with autonomic nervous system blockade. These results indicate that amrinone induced improvement of left ventricular performance are related to actions in diastole, as well as systole. PMID- 8214756 TI - Specific enhancement by fentanyl of the effects of intrathecal bupivacaine on nociceptive afferent but not on sympathetic efferent pathways in dogs. AB - BACKGROUND: Bupivacaine alone, or in combination with opioids, has been shown to provide adequate pain relief without motor paralysis. This study examined the effects of bupivacaine administered intrathecally on sympathetic efferent and A delta- and C-fiber-mediated afferent pathways in dogs and the interactions with intrathecal fentanyl. METHODS: Spontaneous activity in renal sympathetic nerves was observed, as were reflex somatosympathetic responses mediated by A delta and C fibers evoked by supramaximal electrical stimulation of the tibial and radial nerve. Bupivacaine was administered intrathecally in doses of 0.5, 1, 2, and 3.5 mg, each in 0.5 ml, and 7 mg in 1 ml with or without pretreatment with 5.4 mg intrathecal fentanyl (ED25 for depression of C tibial reflexes) in each of five preparations. RESULTS: Bupivacaine caused a dose-dependent inhibition of both A delta- and C-fiber-mediated somatosympathetic responses evoked by tibial nerve stimulation. The depression of radial and tibial nerve reflexes and spontaneous renal sympathetic activity was similar. Pretreatment with fentanyl (5.4 micrograms, intrathecally) depressed tibial C-fiber reflexes by only 23.8% without any significant effect on either tibial A delta or radial A delta and C fiber responses. Fentanyl markedly enhanced the effect of subsequent doses of bupivacaine on tibial A delta and C reflexes without any additional effect on either spontaneous sympathetic activity or radial responses. CONCLUSIONS: Intrathecal bupivacaine has no selectivity for the afferent and efferent pathways, and intrathecal fentanyl acts synergistically to enhance the effect of bupivacaine on the afferent pathway without a measurable effect on sympathetic outflow. PMID- 8214757 TI - Inhibition of plasma membrane Ca(2+)-ATPase activity by volatile anesthetics. AB - BACKGROUND: The precise sites and mechanisms of action of volatile anesthetics remain unknown. Recently, several integral membrane proteins have been suggested as potential targets to which anesthetics can bind at hydrophobic regions. Impairment of cell Ca2+ homeostasis has been postulated as one of the possible mechanisms of anesthetic action. To test these hypotheses, the authors selected the human erythrocyte Ca(2+)-ATPase as a model membrane protein. This enzyme is an integral membrane protein that is instrumental in maintaining Ca2+ homeostasis in the cell in which it is the sole Ca(2+)-transporting system. Thus, any functional alteration of the Ca(2+)-ATPase by anesthetics may lead to serious perturbations in Ca(2+)-regulated processes in the cell. METHODS: The Ca(2+) ATPase activity was measured as a function of increased concentration of four volatile anesthetics: halothane, isoflurane, enflurane, and desflurane. RESULTS: All four anesthetics significantly inhibited the Ca(2+)-ATPase activity in a dose dependent manner. The half-maximal inhibition occurred at anesthetic concentrations from 0.3 to 0.7 vol% at 37 degrees C, which, except for desflurane, is a clinically relevant concentration range. The greater the clinical potency of the volatile anesthetics studied, the less was the concentration required to inhibit the Ca(2+)-ATPase activity. The inhibition was less at 25 degrees C than at 37 degrees C, which is consistent with direct interactions of the nonpolar interfaces of the enzyme with the nonpolar of the portions of the anesthetics. CONCLUSIONS: The authors' findings indicate that the Ca(2+)-ATPase is a suitable model for investigating the mechanism of action of volatile anesthetics on the integral membrane protein, and that this inhibition may be specific. PMID- 8214758 TI - Propofol activates GABAA receptor-chloride ionophore complex in dissociated hippocampal pyramidal neurons of the rat. AB - BACKGROUND: The molecular mechanism of propofol anesthesia has been related to facilitation of the inhibitory neurotransmission mediated by gamma-aminobutyric acid (GABA). In the current study, the authors examined the direct actions of propofol on the acutely dissociated mammalian central neurons. METHODS: Hippocampal pyramidal neurons were dissociated after enzymatic treatment of the brain slices of the rat. Single neurons were voltage-clamped using the whole cell configuration of the patch clamp technique, and drugs were applied with a rapid drug-application system. RESULTS: In the pyramidal neurons voltage-clamped at -60 mV, propofol evoked a transmembrane inward current, which desensitized at high concentrations of the anesthetic. The peak amplitude of the current increased sigmoidally with increasing doses of propofol applied. A least-squares fitting gave a dissociation constant of 1.2 x 10(-5) M and a Hill coefficient of 1.8, thereby indicating that clinical concentrations of propofol evoke the current, and that the anesthetic cooperatively activates the channel. The threshold concentration was less than 10(-6) M. The reversal potential for the current shifted according to the chloride equilibrium potential predicted by the Nernst equation, indicating that the current was carried by chloride ions. Bicuculline and strychnine suppressed the current in a concentration-dependent manner, in which the former was almost 40-fold more potent than the latter. The propofol induced current cross-desensitized with the GABA-induced current, but no such interaction was observed with the glycine-induced current. Ro15-1788 (10(-6) M), an allosteric benzodiazepine antagonist, had no effect on the response. Diazepam (10(-6) M) enhanced the propofol-induced current, but pentobarbital (10(-6) M and 3 x 10(-5) M) did not affect the current. CONCLUSIONS: Propofol at clinically relevant concentrations directly activates the GABAA receptor-chloride ionophore complex in the mammalian central neurons and, hence, increases the chloride conductance, which may contribute to anesthesia produced by the agent. The desensitization of the GABAA receptor in the presence of high concentrations of propofol may result in a suppression of the GABAA inhibitory system. PMID- 8214759 TI - Amrinone attenuates airway constriction during halothane anesthesia. AB - BACKGROUND: Phosphodiesterase (PDE) inhibitors should, in theory, be useful in patients with both cardiac and reactive airway disease who require anesthesia. The effects of the PDE inhibitor, amrinone, on the release of endogenous catecholamines and on airway reactivity to aerosol methacholine challenge were evaluated during thiopental/fentanyl and halothane anesthesia in five mongrel dogs. METHODS: Responses to methacholine aerosol challenge (0.03, 0.075, 0.15, 0.30, 0.75, and 3.0 mg/ml) were measured during four conditions: thiopental/fentanyl anesthesia, thiopental/fentanyl anesthesia with amrinone infusion, halothane anesthesia, and halothane anesthesia with amrinone infusion. Increase in pulmonary resistance (RL) and decreases in dynamic compliances (Cdyn) were calculated for each methacholine dose. Plasma epinephrine and norepinephrine concentrations were measured during thiopental/fentanyl anesthesia with amrinone infusion. RESULTS: Before aerosol challenge, baseline RL and Cdyn did not differ in the four groups. Amrinone significantly attenuated the pulmonary response to methacholine during both thiopental/fentanyl and halothane anesthesia. Plasma catecholamine concentrations did not increase during amrinone infusion. CONCLUSIONS: Amrinone attenuates methacholine-induced airway responses even during halothane anesthesia. These data indicate that isozyme-selective PDE inhibitors hold promise for the perioperative treatment of bronchospasm. PMID- 8214760 TI - Identification of cytochrome P450 2E1 as the predominant enzyme catalyzing human liver microsomal defluorination of sevoflurane, isoflurane, and methoxyflurane. AB - BACKGROUND: Renal and hepatic toxicity of the fluorinated ether volatile anesthetics is caused by biotransformation to toxic metabolites. Metabolism also contributes significantly to the elimination pharmacokinetics of some volatile agents. Although innumerable studies have explored anesthetic metabolism in animals, there is little information on human volatile anesthetic metabolism with respect to comparative rates or the identity of the enzymes responsible for defluorination. The first purpose of this investigation was to compare the metabolism of the fluorinated ether anesthetics by human liver microsomes. The second purpose was to test the hypothesis that cytochrome P450 2E1 is the specific P450 isoform responsible for volatile anesthetic defluorination in humans. METHODS: Microsomes were prepared from human livers. Anesthetic metabolism in microsomal incubations was measured by fluoride production. The strategy for evaluating the role of P450 2E1 in anesthetic defluorination involved three approaches: for a series of 12 human livers, correlation of microsomal defluorination rate with microsomal P450 2E1 content (measured by Western blot analysis), correlation of defluorination rate with microsomal P450 2E1 catalytic activity using marker substrates (para-nitrophenol hydroxylation and chlorzoxazone 6-hydroxylation), and chemical inhibition by P450 isoform selective inhibitors. RESULTS: The rank order of anesthetic metabolism, assessed by fluoride production at saturating substrate concentrations, was methoxyflurane > sevoflurane > enflurane > isoflurane > desflurane > 0. There was a significant linear correlation of sevoflurane and methoxyflurane defluorination with antigenic P450 2E1 content (r = 0.98 and r = 0.72, respectively), but not with either P450 1A2 or P450 3A3/4. Comparison of anesthetic defluorination with either para-nitrophenol or chlorzoxazone hydroxylation showed a significant correlation for sevoflurane (r = 0.93, r = 0.95) and methoxyflurane (r = 0.78, r = 0.66). Sevoflurane defluorination was also highly correlated with that of enflurane (r = 0.93), which is known to be metabolized by human P450 2E1. Diethyldithiocarbamate, a selective inhibitor of P450 2E1, produced a concentration-dependent inhibition of sevoflurane, methoxyflurane, and isoflurane defluorination. No other isoform-selective inhibitor diminished the defluorination of sevoflurane, whereas methoxyflurane defluorination was inhibited by the selective P450 inhibitors furafylline (P450 1A2), sulfaphenazole (P450 2C9/10), and quinidine (P450 2D6) but to a much lesser extent than by diethyldithiocarbamate. CONCLUSIONS: These results demonstrate that cytochrome P450 2E1 is the principal, if not sole human liver microsomal enzyme catalyzing the defluorination of sevoflurane. P450 2E1 is the principal, but not exclusive enzyme responsible for the metabolism of methoxyflurane, which also appears to be catalyzed by P450s 1A2, 2C9/10, and 2D6. The data also suggest that P450 2E1 is responsible for a significant fraction of isoflurane metabolism. Identification of P450 2E1 as the major anesthetic metabolizing enzyme in humans provides a mechanistic understanding of clinical fluorinated ether anesthetic metabolism and toxicity. PMID- 8214761 TI - Thoracic epidural anesthesia increases diaphragmatic shortening after thoracotomy in the awake lamb. AB - BACKGROUND: Prolonged inhibition of diaphragmatic function occurs after thoracic and upper abdominal surgery. It was hypothesized that thoracic epidural anesthesia on the day after a thoracotomy could block inhibitory neural pathways and increase the shortening of costal and crural diaphragmatic segments. METHODS: Pairs of sonomicrometer crystals were implanted into the costal and crural regions of the diaphragm through a right lateral thoracotomy in 14 30-kg, 4-5 month-old lambs. One day after surgery, a thoracic epidural catheter was placed at the T8-T9 level. Regional diaphragmatic shortening normalized to end expiratory length (%LFRC), was measured by sonomicrometry in these awake lambs. Changes in gastric (delta Pgas), esophageal (delta Pes), and transdiaphragmatic (delta Pdi) pressures were measured with transnasal balloon catheters. End-tidal carbon dioxide (FETCO2), costal and crural electromyogram (Edi), and tidal volume (VT) were measured. Inductance plethysmography was used in four lambs to assess relative contributions of the rib cage and abdomen to VT. Control values were obtained during quiet breathing and while rebreathing at up to 10% FETCO2. To block thoracic dermatomes, 1% or 2% lidocaine was injected through the epidural catheter. Measurements were repeated after each lidocaine injection. RESULTS: There was no change of resting length with 1% lidocaine; costal resting length increased by 22% with 2% lidocaine. After 2% lidocaine, costal %LFRC increased from control both during quiet breathing (8.7 +/- 0.7 to 18.1 +/- 1, mean +/- SEM%) and at FETCO2 10% (22.1 +/- 2 to 33.7 +/- 3%). VT during quiet breathing was unchanged after 1% lidocaine but increased from 235 +/- 16 to 283 +/- 28 ml after 2% lidocaine. At 10% FETCO2, delta Pdi was unchanged after 1% lidocaine and decreased from 36.5 +/- 4.3 to 26.3 +/- 4.9 cmH2O after 2% lidocaine. Regional delta Edi was unchanged with both 1% and 2% lidocaine at rest and during carbon dioxide rebreathing. Plethysmography in three lambs showed a reduction in rib cage contribution to tidal volume with 2% lidocaine during quiet breathing. CONCLUSIONS: Improved postoperative tidal volume and diaphragmatic shortening after thoracic epidural blockade may be due to changes of chest wall conformation and resting length and a shift of the workload of breathing from the rib cage to the diaphragm caused by intercostal muscle paralysis. PMID- 8214762 TI - Increased pulmonary perfusion worsens ventilation-perfusion matching. AB - BACKGROUND: Severe exercise and administration of vasopressors may adversely affect pulmonary gas exchange in humans. The role of increases in pulmonary perfusion in worsening ventilation-perfusion (VA/Q) relationships is unclear, however, because concomitant changes in ventilation and alveolar gas composition occur. The purpose of this study was to determine whether increasing of lobar blood flow increased VA/Q heterogeneity in the absence of changes in respiratory parameters. METHODS: Six pentobarbital-anesthetized dogs underwent bilateral thoracotomies, left upper lobectomy, and placement of an electromagnetic flow probe on the left lower lobe (LLL) pulmonary artery, and catheters were inserted into the LLL pulmonary artery distal to the flow probe and confluent trunk of the LLL pulmonary vein. A bronchial divider was inserted to allow separate ventilation of the right lung and LLL. Blood flow to the LLL (QLLL) was increased in random order to two and three times baseline blood flow by opening an arteriovenous fistula and partially occluding the right pulmonary artery. Minute ventilation and alveolar PCO2 of the lobe were unchanged due to use of constant tidal volume and respiratory rate and inspiration of variable amounts of carbon dioxide. VA/Q distributions of the LLL were obtained using the multiple inert gas elimination technique. The tracer inert gas arterial-alveolar difference ([a-A]D) area was used to assess VA/Q mismatch. RESULTS: Increasing QLLL increased mean pulmonary artery pressure in the LLL (LLL Ppa). The PO2 of the LLL pulmonary venous blood remained unchanged, as the mixed venous oxygen tension (PvO2) was markedly increased. VA/Q inequality was increased, indicated by a 40% increase in the [a-A]D area when QLLL was increased to two times greater than baseline QLLL and a 58% increase in the [a-A]D area with three times greater than baseline QLLL. The [a-A]D area was highly correlated with the lobar blood flow (r = 0.97) and LLL Ppa (r = 0.97). CONCLUSIONS: Marked increases in lobar blood flow and Ppa worsened pulmonary gas exchange. The degree of impairment was correlated with the degree of increase in lobar perfusion. However, increased lobar perfusion did not affect LLL pulmonary venous blood oxygenation because the decrease in PO2, due to increased VA/Q mismatch, was opposed by an increase in PO2, due to increased PvO2. PMID- 8214763 TI - Effect of isoflurane and halothane on in vivo ischemia-induced dopamine release in the corpus striatum of the rat. A study using cerebral microdialysis. AB - BACKGROUND: Dopamine is released in large quantities into the corpus striatum during cerebral ischemia and may exacerbate tissue damage. METHODS: Using cerebral microdialysis, the effect of isoflurane on in vivo ischemia-induced dopamine release was studied in rat corpus striatum. Reversible cerebral ischemia was induced using carotid ligatures and induced hypovolemia and was monitored with laser-Doppler flowmetry. Following baseline measurements, 28 normothermic, anesthetized rats were subjected to cerebral ischemia followed by reperfusion. The rats were divided into four groups. Group 1 (n = 10) was anesthetized using chloral hydrate. Groups 2 and 3 received 1.5% end-tidal isoflurane. In group 2 (n = 6), hypotension was left untreated during the reperfusion period, and in group 3 (n = 6), mean arterial pressure was maintained using phenylephrine. Group 4 (n = 6) received 1-1.2% end-tidal halothane. RESULTS: Compared with pre-ischemic levels, large quantities of dopamine (350 x baseline levels) were released in group 1 animals during cerebral ischemia. Compared with group 1, ischemia-induced dopamine release was significantly reduced in group 2 (by 58%) and in group 3 (by 56%), but not in group 4. Group 2 animals were uniformly hypotensive during reperfusion and continued to release substantial amounts of dopamine (8 x baseline levels). In groups 1, 3, and 4, dopamine release decreased to near baseline levels during reperfusion. In group 3, dopamine metabolite production was significantly increased during ischemia, suggesting that enzymatic function and neuronal reuptake of dopamine was preserved. CONCLUSIONS: Isoflurane, compared with chloral hydrate and halothane, inhibits the release of the neurotransmitter dopamine during cerebral ischemia. PMID- 8214764 TI - Left ventricular diastolic function in the normal and diseased heart. Perspectives for the anesthesiologist (1). AB - Attempts to quantitatively describe ventricular function during diastole have been stimulated by the recognition that diastolic mechanics significantly influence overall cardiac performance, and that diastolic dysfunction may precede, or substantially contribute to, abnormalities of systolic function in various pathologic conditions (table 1). Indices of diastolic function can be derived invasively or noninvasively, and focus on the measurement of a diverse and complex set of separate, but intimately interrelated, processes that, while complementary, may not be directly comparable. Measurement of these indices is complicated, because diastolic function depends on several determinants: active, energy-dependent forces (isovolumic ventricular relaxation); passive and dynamic filling characteristics (chamber and myocardial stiffness); and extrinsic factors (left atrial function, ventricular interaction, valvular integrity, pericardial restraint, and myocardial blood flow), as well as other conditions that affect myocardial function during systole (preload, afterload, heart rate, and inotropic state). The diversity of events occurring during diastole indicates that a single index of diastolic function cannot adequately describe this period of the cardiac cycle, and the physiologic implications of diastolic dysfunction may be different, depending on the period of diastole affected (table 1). Thus, assessment of diastolic function is complicated, because of the heterogeneity of the event and the multiple factors that influence it. Despite the inherent potential limitations of indices describing diastolic function, these parameters provide useful references for evaluating the natural history of patients with diastolic heart failure, for assessing the benefits of therapeutic interventions of anesthetic actions, and for enhancing our knowledge of cardiac pathophysiology. PMID- 8214765 TI - Spontaneous ventilation and epidural anesthesia in a patient with a large tracheoesophageal fistula and esophageal cancer undergoing colon interposition. PMID- 8214766 TI - Vicodin-induced fulminant hepatic failure. PMID- 8214767 TI - Why we should use pulse oximetry. PMID- 8214768 TI - On evaluating the efficacy of anesthetic practices: need for attention to clinical details. PMID- 8214769 TI - Sympathetically maintained pain may be rekindled by surgery under general anesthesia. PMID- 8214771 TI - A new method of communication between anesthesiologists. PMID- 8214770 TI - Jet venturi ventilation via the Bullard laryngoscope. PMID- 8214772 TI - A rapid method for negative inspiratory pressure measurement. PMID- 8214773 TI - Changes in life-style in men under sixty years of age before and after acute myocardial infarction: a case-control study. AB - A case-control study was conducted to examine the presence of psychosocial factors before, during, and after acute myocardial infarction (AMI) in Dutch men under sixty years of age. The study included 42 AMI patients and 48 individuals in an age-adjusted sampled control group. The psychological factors included high level of psychological stress, of social isolation, type A1 and A2 behavior, and mental depression. They were assessed by means of the Health Insurance Questionnaire of Greater New York. Univariate analysis indicated that the presence of psychological factors was common at the onset of the myocardial infarction (MI). It clearly diminished, however, after the MI had taken place. In a stepwise logistic regression analysis after adjustment for the independent variables hypertension, cholesterol, and smoking, the following three characteristics were independently related to the risk of MI: no talking (item of social isolation, P = 0.008), need to excel (item of type A1 behavior, P = 0.04), and blue feeling (item of mental depression, P = 0.09). The authors conclude that in men under 60 with AMI, the presence of psychosocial characteristics is common and that this group is going to change its life-style soon after the MI, even without any psychosocial rehabilitation therapy. Follow-up studies investigating the influence of psychological factors on survival and reinfarction should be adjusted for these changes in life-style. PMID- 8214774 TI - Compliance changes in venous insufficiency. AB - In 37 patients (69 limbs) referred to Mayo Clinic's Vascular Center for possible venous valvular insufficiency in the lower limb, calf muscle pump function, calf compliance, and venous refilling times were measured by strain gauge plethysmography techniques. Patient limbs were separated into four categories based on 90% refilling time (T90) following fifteen deep knee bends: normal (n = 16), mild/moderate (n = 28), severe (n = 16), and edema of nonvenous origin (n = 9). Pump function was assessed in actual pumping volumes (mL) and in percent pumping volumes (mL/100 mL), and was reduced in all noncontrol categories. Calf compliance was assessed in actual volume change (mL/mmHg) and in percent volume change (mL/100 mL/mmHg) and was increased in the severe reflux category. Ten study patients had 1 normal category limb and 1 reflux category limb. Paired analysis of these limbs showed pump function to be decreased and calf compliance to be increased in the diseased group limbs. PMID- 8214775 TI - Cardiovascular effects of nifedipine in the dog. AB - This study was designed to measure certain cardiovascular effects of 2 or 11 micrograms nifedipine/kg body weight given intravenously to dogs anesthetized with fentanyl-droperidol-pentobarbital. Parameters measured were: cardiac output, stroke volume, stroke work, systemic arterial pressure and vascular resistance, splenic weight (a measure of venous capacitance), and fractionation of cardiac output to many tissues. In response to doses of nifedipine, systemic vascular resistance decreased, cardiac output and flows to most organs increased, and heart rate, stroke work, and splenic capacitance were unchanged. The flow to the diaphragm increased more than that to other organs. PMID- 8214776 TI - Surface electrocardiogram in the detection of myocardial ischemia during percutaneous coronary angioplasty. AB - The purpose of this study is to examine how frequently myocardial ischemia was manifested on the surface electrocardiogram (ECG) during percutaneous transluminal coronary angioplasty (PTCA) and to select the most sensitive leads for the duration of ischemic ST changes. The study population consisted of 126 patients (pts), 116 men and 10 women, who underwent PTCA for one-vessel coronary artery disease. A 12-lead ECG was recorded in all patients before inflations and at ten-second intervals during each inflation. ST segment deviation, R wave amplitude, and rhythm disturbances were analyzed on all ECG tracings. Ischemic ST changes occurred in 114 pts (90%), 80 with left anterior descending (LAD) artery occlusion, 22 with right coronary artery (RCA) occlusion, and 12 with left circumflex (LCX) artery occlusion (p < 0.01 LAD vs LCX, p < 0.01 RCA vs LCX). Angina pectoris occurred in 74 pts (59%) and coincided with ST changes in 68 of these pts (92%). No significant changes of R wave amplitude were found during balloon inflations. The most sensitive ECG leads for detection of ST elevation were V2 or V3, V4 and V1 for the LAD, leads a VF and II for RCA, and leads III, aVF, or II, and V6 for LCX. The best leads for detection of ST depression were III, aVF and II for LAD, V2 or V3 and aVL for RCA, and V2 or V3, V1, and V4 for LCX. In conclusion, surface ECG represents a simple and very sensitive method for myocardial ischemia monitoring during PTCA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214777 TI - Felodipine and vasomotion physiology. AB - This study concerns the investigation of felodipine's influence on some parameters of vasomotion physiology. Felodipine is a new generation 1,4 dihydropyridine (1,4 DHP) Ca(2+)-entrance blocker with marked vascular selectivity. It was found that felodipine 1-10 microM presents a Ca2+ entrance blocking activity when the bovine aortic smooth muscle is normal or stimulated by K+ 65.4 mM or the alpha-adrenoceptor agonist phenylephrine 1 microM. The same action is observed after nifedipine, a first-generation 1,4 DHP derivative with less angioselectivity in clinical practice. It was also found that felodipine 1 10 microM antagonizes the contraction of the bovine aortic ring that is induced by phenylephrine 10 microM or KCl 65.4 mM. On the contrary, felodipine 1-10 microM increases the contraction of the rat aortic ring that is induced by the same substances. It is known that some 1,4 DHP derivatives that are Ca2+ activators can also behave as Ca2+ blockers and that their final action is dependent upon membrane potential. Now it is also proved that the kind of animal species may also influence the action of the 1,4 DHP derivatives. It was finally found that felodipine increases the catecholamine stores of the sympathetic nerve terminal at the mouse heart (H) and liver (L). Obtained values were as following: control 15.00 +/- 7.7 (H) and 17.72 +/- 3.5 (L). Felodipine 54.50 +/- 4.9 (H) and 41.54 +/- 10.4 (L). Since catecholamine stores depend on secretion (Ca(2+) dependent) and reabsorption (mostly Na(+)-dependent) rates, the increase after felodipine may be attributed to a decreased secretion due to a Ca2+ entry inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214778 TI - Acetylcholine-induced myocardial ischemia without epicardial coronary artery spasm: a possible vasospasm of small coronary arteries--a case report. AB - Small-vessel vasospasm has been speculated upon as a possible cause of chest pain in patients with normal-appearing coronary angiograms. In this report, a patient who experienced typical chest pain during acetylcholine testing, which caused ST segment elevation without epicardial coronary spasm, is presented. This finding suggests that small-vessel vasospasm may be involved in the induction of myocardial ischemia in patients with normal epicardial coronary arteries. PMID- 8214779 TI - The diagnostic importance of computed tomography in aortobronchial fistula--a case report. AB - Aortobronchial fistula secondary to thoracic aortic aneurysm is an unusual cause of hemoptysis. Computed tomography is the diagnostic procedure of choice. An illustrative case is reported. PMID- 8214780 TI - Reversal of gangrenous lesions in the blue toe syndrome with lovastatin--a case report. AB - A seventy-six-year-old man with ischemic heart disease, peripheral vascular disease, and chronic renal failure developed bilateral cyanotic toes, which upon muscle biopsy, were shown to be caused by atheromatous emboli. The probable source was atheromatosis of the abdominal aorta. The toes became gangrenous, but surgical therapy was deferred because the patient was considered a high risk. With lovastatin therapy there was complete healing and except for transient cyanosis related to temporary cessation of therapy, there has been no recurrence for the past thirty months. The possible role of lovastatin in the conservative treatment of this disorder is discussed. PMID- 8214781 TI - What do orthodontic patients really want? PMID- 8214782 TI - "Two-by-four" expression. PMID- 8214783 TI - Videoimaging: the pros and cons. AB - I have tried to make some thoughtful points based on a fair amount of experience in the use of videoimaging, both in research and clinical application. The technical development of computerized videoimaging has progressed greatly in the past several years, in response to the profession's interest in it. While many orthodontists have become interested in this technology because of its potential in communication and marketing, I feel its greatest potential lies in the area of diagnosis and treatment planning. The use of integrated and facial images has allowed me to visualize the face (primarily in profile, although the frontal view can be useful when evaluated and manipulated properly) and recognize particular aspects and patterns of treatment options I had not recognized before (Figures 4 6). Obviously, a great deal of research must be done in the future before we can completely integrate this technology into our treatment of patients. These studies are just beginning. I feel confident that computerized videoimaging will help expand our vision as we strive to deliver the best care possible; nevertheless, we must evaluate this technology rationally and define its strengths and weaknesses just as clearly as we have for our cephalometric tools. PMID- 8214784 TI - Anterior tooth position and motivation for early treatment. AB - During 1989-90, 473 parents of children being screened at an orthodontic graduate clinic completed a self-report form about the child's dental/facial appearance, reasons for seeking care and referral paths. Almost all (85%) of the 313 parents of children under the age of 16 years expressed concern about the appearance of the child's teeth, and 44% reported the child had been teased about this. Only 14% of the parents reported that it was the child who had first noticed the need for treatment. The rank order of reasons for seeking treatment were appearance of teeth (85%), advice of dentist (73%), and appearance of face (46%). Using logistic regression, overjet and malalignment were observed to be significant predictors of the parent-report of the child being teased (odds ratios, OR, 5.5 and 2.4, respectively). Overjet predicted citing facial appearance as the reason for seeking treatment (OR 2.9), while age predicted patient-referral (OR 2.2) and overjet predicted parental referral (OR 3.0). Increased overjet is an important focus for early treatment and might accordingly be expected to influence the value of early intervention. PMID- 8214785 TI - Evaluation of horizontal and vertical differences in facial profiles by orthodontists and lay people. AB - A novel video image processing technique was used to evaluate changes in the facial profile mimicking the effects of various orthognathic surgical techniques. Incremental changes were introduced in male and female images simulating the effects of mandibular advancement or set-back, maxillary advancement or set-back, and maxillary impaction. Twenty-two clinicians and 22 lay people completed questionnaires evaluating their level of sensitivity to changes in the facial profiles and their preferences regarding alternative profiles. The results indicate that in judging realistic color video images, both orthodontists and lay people are sensitive to relatively small horizontal changes in the facial profile. In contrast, orthodontists are less sensitive to relatively large vertical changes but more sensitive to horizontal mandibular changes. PMID- 8214786 TI - An evaluation of smiles before and after orthodontic treatment. AB - The purpose of this investigation was threefold: 1) Determine if a person's smile improves with orthodontic treatment, 2) Determine if the amount of improvement varies among clinicians, and 3) Determine reasons for the variances. Results of this investigation were: 1) In all four categories of evaluation there was a definite improvement in the average scores from the pretreatment to the posttreatment evaluation. 2) The amount of improvement varied from orthodontist to orthodontist. 3) Some patients did not show improvement in one or more of the areas evaluated. 4) A profile photograph is not a reliable source of information to determine what a smile will look like. 5) To maximize the potential for improving a patient's smile, we must consider moving maxillary anterior teeth vertically. PMID- 8214787 TI - Influence of surgical tongue reduction on pressure from the tongue on the teeth. AB - Pressures from the tongue on the teeth were recorded in 21 children and adolescents before and after surgical reduction of the tongue. The recordings were made before surgery, and 6 and 12 months after the operation. Simultaneous measurements were made at the lingual surfaces of the maxillary and mandibular central incisors and at the left first molar, in the rest position and during chewing and swallowing. The method had been used in a previous study of normal cases, which served as a reference. Presurgical pressures recorded in the rest position at the maxillary incisors agreed with measurements recorded in the same location in the reference sample. Measurements recorded during rest in the other locations were somewhat higher than those of the reference group. Pressures recorded before the surgery during chewing and swallowing varied from similar measurements made in the reference group. At the recording 6 months after surgery, resting pressures at the molars were lower than they had been presurgically. No significant differences were found for pressures during chewing. A lower pressure was recorded in one location during swallowing. At the recordings made 12 months after surgery none of the pressures differed significantly from the presurgical values. Resting pressures were, however, lower than they had been before surgery and were closer to those of the reference sample. PMID- 8214788 TI - Case report: three typical cases of glossectomy. AB - Glossectomy, or tongue reduction, is not commonly performed in Japan even though the proportion of patients with Class III skeletal pattern is higher among Japanese people than among Caucasians. The case reports on the ensuing pages follow three patients--one adult with bimaxillary dentoalveolar protrusion, another adult with Class III malocclusion, and a 10-year-old with Class III malocclusion and posterior crossbite--through treatment which included tongue reduction. PMID- 8214789 TI - Midline diastemas: closure and stability. AB - In growing patients, midline diastemas often appear during a transitory stage of development, and then close spontaneously. Occasionally a local cause must be identified and eliminated before the diastema can be closed orthodontically with a stable result. In nongrowing adult patients, the situation is quite different. The following case report shows two patients with similar malocclusions who received similar treatment but whose results were quite different. The patients had relatively rare mandibular midline diastemas in which the causative factor was tongue resting pressure. The report concludes with a description of two posttreatment alternatives to avoid relapse. PMID- 8214790 TI - Bond strength of aged composites found in brackets placed by an indirect technique. AB - The "Thomas" indirect technique for bracket attachment produces an interface not present in direct techniques, that is, an aged composite-sealant interface. Our primary goal was to determine if a weakened interface was produced by a modified (sealant was mixed prior to placement of brackets) Thomas indirect technique when the composite was aged for 7 days. The enamel-bracket system was investigated in vitro by comparison of shear bond strengths for metal and ceramic brackets bonded to bovine teeth by a direct and indirect method. Nearly all specimens failed at the bracket-composite interface and, subsequently, no difference was found between specimens placed by direct or indirect methods. No evidence was found to suggest that an aged composite would predispose the enamel-bracket system to fail at the sealant-composite interface. The ceramic brackets used in this investigation had lower bond strengths then metal ones, but the breaking loads were similar. PMID- 8214791 TI - Clinical effects of reduction of acid concentration on direct bonding of brackets. AB - A total of 600 metal mesh-backed brackets were directly bonded to the anterior teeth of randomly selected orthodontic patients. Prior to bonding, enamel etching was carried out with 37% phosphoric acid on one side and with 2% phosphoric acid on the other side. The etch duration was 30 seconds. After 1 year no statistically significant difference was found between the failure rates of the two etching procedures. The assessment of the Adhesive Remnant Index (ARI) after debonding, however, revealed that the application of 37% acid resulted in significantly higher amounts of residual adhesive left on the teeth. The present study demonstrates that a phosphoric acid concentration of 2% can be sufficient for bracket bonding on anterior teeth. PMID- 8214792 TI - Bond strength of younger and older permanent teeth with various etching times. AB - The purpose of this study was to analyze the tensile bond strength and debonding failure mode in younger and older permanent teeth after etching for 15 and 60 seconds. Bond strength did not change significantly when etching time was increased from 15 to 60 seconds in younger or older permanent teeth. However, regardless of etching time, the bond strength of the older permanent teeth was greater than that of the younger teeth with statistically significant differences. Four types of debonding interface were found; bracket base-resin, within the resin, resin-enamel and enamel detachment. There were no statistically significant differences noted among younger and older permanent teeth with 15 or 60 second etching fracture mode incidence at debondings. Enamel detachment was found only at etching times of 60 seconds. To reduce enamel destruction and save chair time, 15 second etching on either younger or older permanent teeth is suggested. PMID- 8214793 TI - Direct bond brackets: cotton roll versus rubber dam isolation. AB - Forty-four brackets were bonded "in vivo" using cotton roll and rubber dam isolation. Maxillary and mandibular premolars, to be extracted for orthodontic reasons, were used in this study. After bonding, the teeth were retained in the mouth for at least 30 days. They were extracted using surgical elevators. After extraction, the teeth were secured in plastic rings using gypsum and kept in water for 7 days until debonding. A Universal Instron Machine was used to produce a shear force at a speed of 0.1 cm/min until each bracket was removed. No statistically significant differences for debonding strength were observed between the two types of isolation, nor between the buccal and palatal surfaces of the teeth. One hundred percent of the failures occurred at the bracket/composite interface. PMID- 8214794 TI - The role of clinical research in orthodontics. PMID- 8214795 TI - Practice of allergy in the United Kingdom. PMID- 8214796 TI - Eosinophilic pneumonia. PMID- 8214797 TI - Drug therapy for human immunodeficiency virus infection. PMID- 8214798 TI - A 13-month-old child with chronic diarrhea, weight loss, and tachypnea. AB - We present a case of a patient with common variable immune deficiency presenting as the Letterer-Siwe syndrome (disseminated Langerhans cell histiocytosis). To our knowledge, this is the only known patient with this association. The clinical presentation was chronic diarrhea, weight loss, recurrent infections, hepatosplenomegaly, and interstitial pneumonitis. Laboratory evaluation revealed evidence of immunodeficiency, with agammaglobulinemia and diminished number and function of T cells. The diagnosis of Langerhans cell histiocytosis was confirmed by electron microscopic examination of the lung biopsy specimen demonstrating Birbeck granules in the cells of the infiltrate. It is known that patients with the combined immunodeficiency syndrome may present as disseminated Langerhans cell histiocytosis, and the case presented demonstrates that patients with common variable immune deficiency may similarly present. It is advisable that patients newly diagnosed with Langerhans cell histiocytosis be evaluated to screen for immunodeficiency. Conversely, patients presenting with combined immunodeficiency or common variable immune deficiency may display features of disseminated Langerhans cell histiocytosis. These associations must be considered in newly diagnosed immunodeficient patients. PMID- 8214799 TI - Acute eosinophilic pneumonia following intentional inhalation of Scotchguard. AB - We present a case of acute pneumonia associated with eosinophilic infiltration of the lung accompanied by respiratory failure preceded by repetitive inhalation abuse of Scotchguard. The patient responded to mechanical ventilation and corticosteroid therapy. This case is similar to other idiopathic acute eosinophilic pneumonia cases except for identifying an associated chemical abuse. This case supports the use of diagnostic bronchoalveolar lavage in acute respiratory failure and presents a previously unreported complication of the inhalation abuse of 1,1,1-trichloroethane. PMID- 8214800 TI - Cytokines and their role in the pathogenesis of severe food hypersensitivity reactions. AB - Cytokines are proteins produced by one cell that are capable of altering the behavior of another cell. Their biologic effects are both pleomorphic and redundant. A number of cytokines have been implicated in the genesis of allergic reactions, including IL-4, IL-5, IL-6, and tumor necrosis factor (TNF). In contrast, other cytokines such as gamma interferon (gamma-IFN) may have biologic actions that act to limit allergic responses. In studies on patients with severe food allergy, we have found cytokine production from peripheral T cells to be abnormal following mitogenic stimulation. These lymphokine abnormalities may contribute to the elevation in IgE and the eosinophilia seen in severe food allergy. PMID- 8214801 TI - Influence of dietary manipulation on incidence of atopic disease in infants at risk. AB - Of 5,500 newborn infants whose family histories were screened, 900 were found to have anamnestic risk. Cord-blood IgE was evaluable in 4,677 of these newborns, of which 394 had levels > or = 1 IU/mL; 84 infants had both anamnestic risk and elevated cord-blood IgE levels. Parents of infants with anamnestic risk were informed of their child's risk of atopy. Additionally, for 391 infants at two of the three participating hospitals, a preventive diet was prescribed that recommended breastfeeding for the first 6 months of life, with maternal diet restricted to no more than 200 dL of cow milk per day, no more than one egg per week, and no tomato, fish, shellfish, nuts, or foods allergenic to the mother. Only soy formula was recommended, and introduction of solid foods was also carefully prescribed. Furthermore, doctors recommended against exposure to tobacco smoke, animal allergens, and early entrance into daycare. Evaluable infants whose parents complied with the prescribed diet were found to have a lower incidence of atopy during the first year of life (13.3%, n = 158) than infants whose parents had ignored the prescribed diet (54.7%, n = 86) or infants whose parents were offered no dietary recommendations (28.9%, n = 218). Differences between the compliant group and the two groups with unrestricted diets were significant, indicating that this prescribed diet may protect against or delay onset of food allergies during the first year of life. PMID- 8214802 TI - Effect of loratadine on human eosinophil function in vitro. AB - We investigated the in vitro effect of loratadine, a new nonsedating H1 histamine antagonist, on the eosinophil functions of chemotaxis, superoxide anion (O2-) generation and eosinophil cationic protein (ECP) release, using purified eosinophils obtained from allergic patients. Loratadine significantly attenuated platelet-activating factor (PAF)-induced eosinophil chemotaxis and O2- generation at therapeutic concentrations (equivalent to serum concentrations after single oral administration of 20 mg or 40 mg). Loratadine, however, had no effect on PAF induced ECP release. These findings suggest that loratadine has a direct inhibitory effect on eosinophil activation and may be beneficial in the therapy of allergic disorders with its anti-allergic properties. PMID- 8214803 TI - Adverse reactions to food additives. AB - Food additives can induce a wide range of adverse reactions in sensitive individuals. A prevalence of 0.03% to 0.23% is estimated. The complexity of the different pathophysiologic mechanisms possibly involved in the allergic (immunologic) or in the intolerant (nonimmunologic) reactions to food additives continues to create great difficulties in the understanding of such conditions. From the clinical point of view it is useful to make a distinction between an intolerance reaction and intolerance provocation. The pathogenic mechanisms of adverse reactions to the azo dye tartrazine and to sulfite preservatives are discussed briefly. Due to the lack of reliable skin or in vitro tests, the diagnosis of an intolerance to food additives is still based on placebo controlled oral provocation tests. Two typical cases of a "restaurant syndrome" due to sulfite allergy or sensitivity are described, as well as a case of disulfite-induced urticaria-vasculitis and a case of anaphylactoid purpura associated with tartrazine and benzoates. PMID- 8214805 TI - Density change of neutrophils from allergic subjects by granulocyte-macrophage colony stimulating factor. AB - We investigated neutrophil density change by platelet activating factor or granulocyte-macrophage colony-stimulating factor (GM-CSF). Although PAF significantly converted neutrophil density, there was no significant difference in density change between allergic subjects and normal subjects by platelet activating factor. Neutrophils from allergic subjects, however, were significantly converted by GM-CSF when compared with neutrophils from normals (P < .05). We conclude that neutrophils from allergic subjects are more sensitive to density change by GM-CSF than neutrophils from normal subjects. This might be due to preactivation or priming by biologic agents. PMID- 8214804 TI - Local hyperthermia and nasal irrigation for perennial allergic rhinitis: effect on symptoms and nasal airflow. AB - Local hyperthermia or inhalation of heated water vapor is often recommended as a home remedy for various nasal disorders such as the common cold and allergic rhinitis. With technical advances in vapor generation, water can be heated to a range of 41 degrees C to 43 degrees C with variation in particle size. The effect of inhaled heated vapor treatments was studied in patients with perennial rhinitis for changes in nasal airflow and patient perception of symptoms. Thirty symptomatic patients underwent three treatments at weekly intervals: (1) a large particle heated water vapor at 43 degrees C for 20 minutes with a particle size of 4 to 8 microns, (2) a molecular water vapor at 41 degrees C for 20 minutes which is a vapor phase, and (3) nasal irrigation. Nasal airflow increased after both vapor treatments at four and six hours (P < .05) whereas airflow decreased after simple nasal irrigation treatment. Rhinitis symptoms improved after vapor treatments but not with nasal irrigation. Patients preferred the molecular water vapor treatment over the large particle vapor treatment and nasal irrigation by 2:1 margin. This study demonstrated the usefulness of heated vapor treatments in improving rhinitis symptoms and nasal airflow. PMID- 8214806 TI - The lesson of agammaglobulinemia 40 years after Bruton's discovery. AB - Forty years after Bruton's discovery, the spectrum of primary defects of immunoglobulins has been largely extended and characterized. An increasingly more accurate recognition of the basic pathogenetic mechanisms of disease has helped to design more effective drugs and therapeutic strategies for patients with both primary and secondary immune deficiencies. In recent years, major advances in molecular biology have allowed characterization of the genetic basis of many primary immunodeficiencies, resulting in more accurate genetic counseling and leading to the first successful application of genetic therapy to the treatment of a human disease. PMID- 8214807 TI - [Viral theory of atherosclerosis. Role of cytomegalovirus]. AB - The multifactorial aetiology of atherosclerosis is nowadays well established. In parallel with confirmation of the lipidic hypothesis, a tumoral theory for this pathology was built up during the past decade. This theory considers atheroma a benign tumor. Among agents that can induce cell proliferation, oncogenic viruses seem to be the most efficient. In this review, we present several works suggesting viral involvement in atherosclerosis. The viral theory is based not only on clinical and epidemiologic data, but also on cell and molecular biology research. These three complementary approaches have established a relationship between herpes viruses and the atherogenic process. Cytomegalovirus (CMV) seems to be the suspect in human atherosclerosis. Several studies of the effects of CMV on cells involved in atheroma, especially smooth muscle cells and endothelial cells, are consistent with a possible role of this virus in atherosclerosis. This paper presents not only recent research developments in this increasingly explored field, but also questions that remain to be elucidated and the consequences of the viral theory of atherosclerosis. PMID- 8214808 TI - [Comparative evaluation of unfractionated and low molecular weight heparins. Results of the French Etalonorme interlaboratory quality control]. AB - Four recent interlaboratory surveys have been conducted by the French National "Etalonorme" Group of Quality Control in Haematology, involving about 3,800 laboratories working in coagulation. They have been concerned with human lyophilised plasma samples heparinized in vitro either with unfractionated heparins (UFH), or with low molecular weight heparins (LMWH) (Fragmin 89 D, and Fraxiparin 90 A). The doses added simulated therapeutic situations or were on the border-line of over- or underdosage: UFHs 89 B3/B4, 0.14 and 0.22 IU/ml; 89 C3/C4, 0.3 and 0.4 IU/ml respectively; LMWHs: D3-A3, 0.6; and D4-A4, 1.2 IU/ml. Automated partial thromboplastin times (APTT) were prolonged at these high doses of LMWH, due to noticeable residual anti-IIa activity. A relationship between APTT and heparinaemia was observed with both types of heparin; sensitivities of cephalin reagents to heparin were also noted, but they were different for UFH compared to LMWH. Dispersion on APTT results was still high (CV: 12-23% for the UFH samples, 12-19% for the four LMWH samples). Dispersion on heparin determinations was higher for UFH than for LMWH, even for lower anti-IIa activity, but they involved more heterogeneous assays. The anti-Xa activity for LMWH samples was mainly determined using clotting assays (70% of the laboratories) with larger dispersions (CV: 32-37%), than those observed on amidolytic assays (CV: 28%); however, these amidolytic assays were performed in 90% of the laboratories with only two reagents available from a single manufacturer. The clotting techniques, more than the colorimetric assays, seemed to underestimate the high heparinaemias.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214810 TI - [Correlations between clinical pharmacodynamics and pharmacokinetics of cisplatin and etoposide]. AB - Currently, the dose of anticancer drugs is adjusted according to patient body surface area, although the best criterion for dose adjustment seems to be the plasma concentration of the drug, since a correlation has been established between plasma concentration and efficacy for several drugs. We report here similar results with etoposide and cisplatinum. The plasma concentration and the area under the curve (AUC) of etoposide and platinum (Pt) were higher in responders compared to non-responders, and etoposide clearance was higher in responders. The etoposide toxicity (assessed by the polymorphonuclear blood count) was higher in responders. There was a good correlation between the Pt concentration and creatininaemia. The AUC for Pt was significantly higher in patients with nausea and vomiting. There was no correlation between the infected dose of either drug and efficacy or toxicity. It is not possible to assign efficacy to either compound since they were injected simultaneously. We conclude that when the plasma etoposide or platinum concentrations are low, tumour response is unlikely. PMID- 8214809 TI - [Enzymatic determination of cholesterol in bile without interference of bilirubin]. AB - The authors describe an enzymatic method for cholesterol determination in bile after elimination of bilirubin interference. During sample pretreatment, bilirubin is oxidized by hydrogen peroxide produced by adding glucose, glucose oxidase and peroxidase. Excess hydrogen peroxide is oxidatively coupled with 4 amino-antipyrine and a phenolic derivative (P-hydroxybenzoic acid). Cholesterol is then measured by use of a CHOD-PAP kinetic fixed-time method adapted to two different centrifugal analyzers (Multistat and Monarch IL). This method has a good within-run precision (CV = 1.6%) and good linearity (up to 23 mmol/l). Results have been compared to gas-liquid chromatographic (method selected by the Lipids-Lipoproteins Commission of the SFBC). The allometric regression line is: y = 1.016 x - 0.07 with r = 0.9975 (P < 0.001). PMID- 8214811 TI - [Malaria: two complementary methods for Plasmodium detection in hospital practice]. AB - In non-endemic areas, malaria diagnosis must be reliable and sensitive. Using acridine orange staining of centrifuged parasites (QBC) and Giemsa- stained thin blood films, we detected Plasmodium in 170 blood samples (158 samples were positive with both methods; 7 were positive with the QBC technique only and 5 were positive with the thin smear only). The QBC technique is useful for rapid screening and thin smear is necessary for Plasmodium identification and parasitaemia determination. The two complementary methods provide rapid and efficient diagnosis of malaria in non-endemic areas as well as control of parasitaemia following therapy. PMID- 8214812 TI - [Anti-cytoplasm antibodies to polynuclear neutrophils: specificity in renal vasculitis]. AB - We present a retrospective study of all patients with a positive anti-neutrophil cytoplasm autoantibodies (ANCA) result from July 1987 to December 1990. The aims of the study were to assess specificity of ANCA in renal vasculitis and to correlate ANCA immunofluorescence subtypes with clinical aspect, diagnosis, severity and outcome. Anti-myeloperoxidase antibody (A-MPO) was sought in 31 cases. Specificity was 86% and false-positive results were 11%. ANCA subtypes varied with the clinical picture. C-ANCA were more often present when renal vasculitis was associated with pulmonary and ear, nose and throat involvement; P ANCA were more often present when there was no respiratory tract involvement. Thus C-ANCA were preferentially associated with Wegener's granulomatosis and P ANCA with microscopic polyarteritis and pauci-immune necrotizing and crescentic glomerulonephritis. No correlation was found between ANCA subtypes and severity or outcome. A-MPO were positive in 14 cases (especially in micropolyarteritis and necrotizing glomerulonephritis). PMID- 8214813 TI - Determination of erythrocyte protoporphyrin with a hematofluorometer: interference due to malarial parasitaemia. PMID- 8214814 TI - Immunological methods for the detection of structural components and metabolites of bacteria and fungi in blood. AB - This review compares the clinical usefulness of immunological methods for the detection of structural components and metabolites of bacteria and fungi. Bacterial antigens (especially those of Mycobacterium, Neisseria, Staphylococcus aureus, Yersinia enterocolitica, Escherichia coli, Salmonella, Chlamydia, and Brucella) are best detected by enzyme-linked immunosorbent assay. Methods involving antibodies are more expensive and are effective only when performed in series. The detection of antibodies that recognize S aureus teichoic acid merely confirms the presence of a metastatic complication. Tissue invasion by Candida albicans is not yet reliably detectable by the presence of a specific antigen. Simple, but not completely reliable methods are available such as the latex test for mannans detection and/or agglutination with liposomes for detecting 48-kDa cytoplasmic protein antigen and an assay for detecting enolase antigen. A latex agglutination test has also been developed for the mannans antigen of Aspergillus and for Cryptococcus neoformans capsular polysaccharide; the latter test is more cost effective. The sensitivity of both tests is improved by serial assays. A negative finding with hemagglutination-based antibody tests rules out C albicans infection, and titers of 1/640 or higher have been associated with disseminated infection by Aspergillus. Concentrations of C albicans blastopore antigen antibodies higher than 400 IU/ml can be seen in disseminated candidiasis. High concentrations of endotoxin are indicative of imminent septic shock. Some biological indicators (C reactive protein, angiotensin converting enzyme, fibronectin, elastase-alpha 1-antitrypsin complex, tumor necrosis factor and interleukin-6) have been used to rule out a bacterial cause of fever.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214815 TI - [Mobile species of the genus Aeromonas: difficulties of identification and pathogenicity]. AB - Sixty-two Aeromonas strains (39 of clinical and 23 of environmental origin) were identified. The suicide phenomenon and autoagglutination were studied. Identification is based on esculin hydrolysis; fermentation of arabinose salicin, sucrose and mannitol; gas production from glucose, indole and beta hemolysis; Voges-Proskauer and decarboxylation reactions; and finally resistance to cephalothin (30 micrograms) and colistin (4 micrograms/ml). Thirty-four per cent of A hydrophila, 33% A caviae, 28% A veronii subspecies sobria, 3% A jandaei, 2% A veronii subspecies veronii were accurately identified. Also, several new species were identified such as A trota, A enteropelogenes, A schubertii, A ichthiosmia, according to the more recently proposed taxa. This identification scheme could enhance our knowledge concerning virulence factors, pathogenicity and environmental distribution. PMID- 8214816 TI - Flow dynamics across end-to-end vascular bypass graft anastomoses. AB - In this article, a numerical simulation of steady flow across an end-to-end vascular bypass graft anastomosis is presented. In vitro experiments were performed to determine the variations in the conduit cross section at the anastomosis. Penrose surgical drainage tubing was used to simulate an artery and was anastomosed with Polytetrafluoroethylene (PTFE) vascular grafts using a continuous suturing technique. Artery to artery anastomosis was simulated by suturing two Penrose tubing segments. The anastomotic specimens were subject to static transmural pressure in the physiologic range to determine the instantaneous diameter and compliance as a function of the distance from the anastomotic site. The experimentally determined geometries were used to simulate steady flow through an end-to-end anastomosis using the finite analytic (FA) numerical solution technique. The results demonstrated a region of flow separation 2 mm distal to the Penrose tubing-Penrose tubing anastomosis (simulating an artery-artery anastomosis) at higher transmural pressures. Moreover, wall shear stresses increased proximal to the anastomosis in flow from the Penrose tubing to the graft. In flow from the graft to the Penrose tubing, low wall shear stresses were observed distal to the anastomosis. Flow separation was observed distal to the anastomosis at higher transmural pressures with uniform inlet velocity condition. The region of low shear stress in flow from PTFE graft to the Penrose tubing was located nearer to the anastomosis with thin wall grafts than that with standard wall thickness grafts. Our steady flow model studies suggest a correlation between regions of low wall shear stress and the development of anastomotic neointimal fibrous hyperplasia in end-to-end anastomoses. PMID- 8214817 TI - Modification of DiFrancesco-Noble equations to simulate the effects of vagal stimulation on in vivo mammalian sinoatrial node electrical activity. AB - We present a new mathematical model for vagal control of rabbit sinoatrial (SA) node electrical activity based on the DiFrancesco-Noble equations. The original equations were found to be unstable, resulting in progressive cycle by cycle depletion or accumulation of ions in intra- and extracellular compartments. This problem was overcome by modifying the maximum Na-K pump current and the time constant for uptake of intracellular calcium. We also included a formulation for the acetylcholine (ACh)-activated potassium current which was consistent with experimental data. This formulation was based on kinetics first proposed by Osterrieder and later modified by Yanagihara. The resulting model exhibits cycle cycle ionic stability, and includes an ACh-activated potassium current which accurately reproduces experimentally observed effects of vagal stimulation on both the membrane potential and its time-derivative. Simulations were performed for both brief-burst and prolonged vagal stimulation using simplified square wave profiles for the concentration of ACh in the synaptic cleft space. This protocol permits the isolation of cardiac period dynamics caused by changes in membrane potential and intra- and extracellular ionic concentrations from those caused by other mechanisms including the dynamics of ACh release, diffusion, hydrolysis and washout. Simulation results for the effects of brief-burst single cycle stimulation on the cardiac period agree closely with experimental data reported in the literature, accurately reproducing changes in membrane potential and the phasic dependency of the response to the position of vagal stimulus bursts within the cycle. Simulation of the effects of prolonged vagal stimulation accurately reproduced the steady-state characteristics of heart period response, but did not yield the complex multimodal dynamics of the recovery phase, or the pronounced post vagal tachycardia observed experimentally at the termination of the stimulus. Our results show that the major chronotropic effects of vagal stimulation on the SA cell membrane can be explained in terms of the ACh activated potassium current. The effects of this membrane current however are generally fast acting and cannot contribute to any long lasting dynamics of the cardiac period response. The modified DiFrancesco-Noble model presented in this article provides a valuable theoretical tool for further analysis of the dynamics of vagal control of the cardiac pacemaker. PMID- 8214818 TI - Multistage enhancement of surface recordings of canine gastric electrical signals. AB - This article describes a multistage signal processing scheme to enhance the quality of canine gastric signals recorded from the abdominal surface. The scheme involves a cascade application of linear prediction followed by a nonlinear processing known as alpha-TM filtering. The linear prediction is used to separate, in the minimum mean square error sense, the slow wave from other uncorrelated interference signals. We make novel use of the order versus frequency response characteristics of linear predictors to achieve this separation. The nonlinear filtering is used to suppress the residual wide band impulsive noise. Our studies have indicated that such an optimized signal enhancement scheme produces a clean time domain signal, which is easy to interpret visually. It not only preserves the periodicity of the slow wave, but also seems to track any irregularities in the periods. We believe that this last feature, namely the potential to track nonstationarities in the signal, is the main contribution of our approach. PMID- 8214819 TI - Noninvasive blood pressure measurement on the temporal artery using the auscultatory method. AB - Blood pressures in the temporal artery of five normotensive subjects were recorded using a modified auscultatory setup. The setup comprised a pediatric cuff to occlude the artery and a piezoelectric contact microphone to record the Korotkoff sounds. Both the cuff and microphone were held in their respective positions with an adjustable head band. The recordings were taken under four different conditions: the subject lying supine, the subject sitting at rest, the subject sitting immediately after exercise and the subject moving the head gently. These recordings were compared with readings from the brachial artery, obtained with a commercially available automatic blood pressure measuring device. Korotkoff sounds were analyzed in the time and frequency domain. Results indicate that Korotkoff sounds in the temporal artery are much smaller in amplitude, and do not exhibit the same distinctive phases as those of the brachial artery. Despite these differences, these sounds can be used to detect blood pressures at head level. The accuracy of the readings was within +/- 10%. Successful readings were also obtained with gentle head motions, demonstrating that this setup has the potential to be developed into an ambulatory blood pressure monitoring system. PMID- 8214820 TI - Continuous blood density measurement for hemodynamic monitoring: an analysis of its accuracy and sensitivity. AB - Continuous measurement of arterial blood density after bolus injection of fluids of different density into the right atrium has been used to measure cardiac output and mean transit time through the central circulation. The transit time distribution for density, however, differs from that for plasma-phase tracers such as indocyanine green. This difference may yield important information about red cell transit times through the microcirculation. We analyzed the potential of the density technique to resolve small changes in transit time distributions. Rayleigh's Method was used to calculate the relationship between density distribution within the U-tube and frequency of oscillation. Fourier integral transformation of a functional representation of indocyanine green dye curves provided an estimate of amplitude versus frequency for likely input density signals. We found that the ability of the densitometer to accurately follow blood density changes depends upon physiologic parameters associated with the experimental animal and upon the physical characteristics of the densitometer itself. Even for small animals, such as a rabbit, the densitometer theoretically has the ability to accurately follow rapid density changes over time. PMID- 8214821 TI - Factors affecting perceived tumor volumes in magnetic resonance imaging. AB - Irregularly structured brain tumors, such as glioblastomas, challenge attempts to visualize and quantify their three dimensional structure. Magnetic resonance imaging (MRI) represents one tool for attempting to noninvasively track tumor size. MR images demonstrate widely varying perceived tumor margins. In addition, adjunct therapies, such as the administration of steroids, greatly affect the volumes perceived in images formed by certain pulse sequences. In this study tumors were grown in 15 dogs and the tumor size tracked for a period of time. The dogs were placed on dexamethasone for a week and another series of scans was obtained. No other therapies were provided. The data for visualized tumor size are provided for T1, T2, and proton density. Weighted images are provided and the relationships between the scans are discussed. PMID- 8214822 TI - Muscle electric activity. I: A model study on the effect of needle electrodes on single fiber action potentials. AB - Needle recorded electromyographic signals can be expected to be influenced by the presence of the needle, the electrical double layer at the metal-electrolyte interface, and by an edematous layer around the needle electrode. The magnitude of each of these effects is derived from a cylinder symmetrical volume conductor model. Analytical solutions of Laplace's equation have been derived. These are used for simulating single muscle fiber action potentials (SFAPs) recorded by a typical single fiber electrode. The results indicate that there is no short circuiting effect, in spite of the presence of a highly conducting needle shaft, which is due to the high impedance of the electrical double layer. The insulating properties of the double layer cause the SFAP amplitudes to increase, when the muscle fiber passes the electrode at the side of the leading-off point. The edematous layer counteracts this increase depending on the thickness and the conductivity of this layer. Only slight SFAP wave-form changes are found. PMID- 8214823 TI - Muscle electric activity. II: On the feasibility of model-based estimation of experimental conditions in electromyography. AB - From regular one-channel registrations of single muscle fiber action potential no measures on the recording configuration can be derived. When multichannel recordings are made, experimental parameters such as the distance between muscle fiber and needle electrode can be estimated. With the help of a volume conductor model, the single fiber activity at each of the electrodes can be predicted as a function of the recording conditions. Within known physical and physiological constraints such a model approach can be inverted (the inverse model) and used to estimate basic experimental conditions. From eight simultaneous single fiber action potential recordings we estimated (a) the distance between fiber and needle, (b) the axial position of the needle with respect to the muscle fiber, (c) a factor related to the muscle tissue anisotropy, and (d) a factor combining the muscle fiber diameter and the effective muscle tissue conductivity. With the help of a model describing the influence of the needle shaft it is made plausible that the needle inhomogeneity influences the results of the proposed procedure. PMID- 8214824 TI - Nonlinear summation of junction potentials in a three-dimensional syncytium. AB - A three-dimensional "cable" equation with reversal potentials is derived for an infinite syncytium. Its solution is found analytically by using Green's function methods for the special case of two impulsive conductance changes activated at different "points" in space. It is shown that junction potentials generated at different sites in the syncytium do not in theory sum linearly. PMID- 8214825 TI - Shear-augmented dispersion in non-Newtonian fluids. AB - The rate of spread of a passive species is modified by the superposition of a velocity gradient on the concentration field. Taylor (18) solved for the rate of axial dispersion in fully developed steady Newtonian flow in a straight pipe under the conditions that the dispersion be relatively steady and that longitudinal transport be controlled by convection rather than diffusion. He found that the resulting effective axial diffusivity was proportional to the square of the Peclet number Pec and inversely proportional to the molecular diffusivity. This article shows that under similar conditions in Casson and power law fluids, both simplified models for blood, and in Bingham fluids the same proportionalities are found. Solutions are presented for fully developed steady flow in a straight tube and between flat plates. The proportionality factor, however, is dependent upon the specific rheology of the fluid. For Bingham and Casson fluids, the controlling parameter is the radius of the constant-velocity core in which the shear stress does not exceed the yield stress of the fluid. For a core radius of one-tenth the radius of the tube, the effective axial diffusivity in Casson fluids is reduced to approximately 0.78 times that in a Newtonian fluid at the same flow. Using average flow conditions, it is found that the core radius/tube radius ratio is 0 (10(-2)) to 0 (10(-1)) in canine arteries and veins. Even at these small values, the effective diffusivity is diminished by 5% to 18%. For power law fluids, Pec2 dependence is again found, but with a proportionality constant dependent upon the power law exponent n.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214826 TI - Body volume changes during simulated microgravity: auditory changes, segmental fluid redistribution, and regional hemodynamics. AB - Space adaptation syndrome (SAS), manifested by cephalad fluid shifts, spacial disorientation, nausea, and vomiting, is of varied expression and uncertain etiology. One theory is that fluid shift to the upper body alters the function of the vestibular apparatus to create an entity similar to Meniere's disease. Since clinical vestibular dysfunction syndromes are mirrored by altered cochlear function, this experiment was undertaken to study the relation between fluid redistribution and the auditory effects of initial antiorthostatic bed rest. Manual and bone audiometry, impedance tympanometry, and brain-stem evoked potentials were used to monitor auditory changes prior to, during, and following short term exposure to -6 degrees head down tilt. Impedance plethysmography was performed to assess the segmental and intracranial fluid redistribution and hemodynamic changes during short-term head down tilt simulated microgravity. Even though significant cephalad fluid shift produced marked intracranial congestion and the subjects exhibited SAS symptoms, no clinically significant changes in the auditory system could be detected. PMID- 8214827 TI - Coronary flow patterns in normal and ischemic hearts: transmyocardial and artery to vein distribution. AB - The dynamics of the transmyocardial coronary flow patterns during normal and ischemic conditions are complex and relatively inaccessible to measurements. Therefore, theoretical analyses are needed to help in understanding these phenomena. The proposed model employs compartmental division to three layers, each with four vessel-size compartments which are characterized by resistance and compliance. These compartments are subjected to the extravascular compressive pressure (ECP) generated by cardiac contraction, which by modifying the transmural pressure causes changes in cross-sectional area of the vessels in each compartment continuously determining the resistance and capacitance values. Autoregulation and collaterals are also included in order to simulate the flow patterns during regional ischemia. Using these features, the model predicts the typical out of phase arterial and venous flow patterns. Systolic collapse of the large intramyocardial veins during the normal cycle, as well as systolic arteriolar collapse during ischemia are predicted. The transmural flow during ischemia is characterized by alternating flows between the layers. The ECP is considered here is two ways: (a) as a function of left ventricle (LV) pressure, decreasing linearly from endocardium to epicardium and (b) as the interstitial fluid pressure, employing a multilayer muscle-collagen model of the LV. While both of these approaches can describe the dynamics of coronary flow under normal conditions, only the second approach predicts the large compressive effects due to high ECP obtained at very low cavity pressure, resulting from significant muscle shortening and radial collagen stretch. This approach, combining a detailed description of transmural coronary circulation interacting with the contracting myocardium agrees with many observations on the dynamics of coronary flow and suggests that the type of LV mechanical model is important for that interaction. PMID- 8214828 TI - Hand injuries in children presenting to a pediatric emergency department. AB - STUDY OBJECTIVE: To study the epidemiology of pediatric hand injuries. DESIGN: Retrospective chart review. SETTING: Emergency department of a children's hospital. PARTICIPANTS: All patients with a final diagnosis of hand injury from July through December 1989. INTERVENTIONS: None. RESULTS: Four hundred sixty-four patients (287 boys and 177 girls; median age, 10 years) with a total of 477 hand injuries were enrolled in the study. The most common types of injuries were lacerations (38.1%), soft tissue injuries (28.7%), and fractures (19.3%) and sprains (8%); most (60.8%) were sustained at home. Children with lacerations and burns were significantly younger than those with other types of hand injuries (P < .0001). Children with fractures, sprains, and sports injuries were significantly older than those with other types of hand injuries (P < .001). The fifth finger was the most commonly fractured digit (37%), and the fifth metacarpal was the most commonly fractured bone (P < .01). Boys were more likely than girls to sustain sports-related injuries (P < .05) and hand injuries resulting from first fights (P < .01). More hand injuries were associated with football than with any other organized sport (P < .01). All but 16 children (3.4%) were managed as outpatients. CONCLUSION: Hand trauma accounts for a significant number of pediatric ED visits. Physicians caring for children in the ED setting must be prepared to manage a wide spectrum of pediatric hand injuries. PMID- 8214829 TI - A randomized, controlled trial of radiograph ordering for extremity trauma in a pediatric emergency department. AB - STUDY OBJECTIVES: The objectives of this study were to determine whether triage nurses using the Brand protocol would order fewer radiographs than would physicians carrying out standard practice procedures, without missing an increased number of joint or bone injuries; the test characteristics and the interobserver reliability of the Brand protocol; and whether having triage nurses order radiographs could reduce total patient waiting time in the emergency department. DESIGN: Randomized, controlled trial. SETTING: The ED of a free standing children's hospital with approximately 55,000 visits annually. TYPE OF PARTICIPANTS: Children less than 18 years of age who had a history of extremity trauma in the preceding seven days. INTERVENTIONS: Triage nurses applied the Brand protocol to determine the need for a radiograph. MEASUREMENTS AND RESULTS: Of the Brand protocol group, 81.9% had radiographs ordered compared with 87.1% of the control group (P = .03). The percent of positive radiographs was 40.8% in the Brand protocol group compared with 42.6% in the control group (P = .21). There were 3.2% (16) missed radiographic findings in the Brand protocol group compared with none in the control group (P < .001). Patients randomized to the Brand protocol group spent 3.3 hours in the ED compared with 3.6 hours for the control group (P < .001). CONCLUSION: Having triage nurses use the Brand protocol reduced the number of radiographs ordered but at the same time increased the number of missed radiographic findings. However, having triage nurses order radiographs also significantly shortened waiting time in the ED. PMID- 8214830 TI - Substance abuse in adolescent trauma. AB - STUDY OBJECTIVE: To determine if there is a significant prevalence of drug or alcohol use among adolescents evaluated for significant acute trauma. DESIGN: A prospective, age-matched controlled study over a 20-month period. SETTING: Urban pediatric emergency department in a Level I pediatric trauma center. PARTICIPANTS: Patients between 13 and 19 years of age requiring admission to the trauma service following evaluation in a pediatric ED and an age-matched control group of asthmatic patients. RESULTS: A total of 134 patients (mean age, 14.8 years) were admitted for trauma-related injuries, and 22 of 65 (34%) were positive for alcohol or drugs of abuse. The mean age of patients with a positive toxicology screen was 15.4 years. Most commonly detected drugs were alcohol (eight), benzodiazepines (eight), cocaine (five), and cannabinoids (four). The number of positive screens in the trauma group (22 of 65) was significantly higher than controls (one of 49) (P < .001). This remained statistically significant even when those trauma patients not screened were assumed to have a negative toxicology screen (22 of 134 versus one of 49) (P < .01). There was also a significantly higher number of positive toxicology screens among adolescents with an intentional versus unintentional mechanism of injury (21 of 71 versus one of 63) (P < .001). CONCLUSION: A significant number of adolescents admitted to the hospital for trauma-related injuries have a toxicology screen positive for alcohol or drugs of abuse. A toxicology screen should be a standard laboratory test in adolescents involved in significant trauma, especially if the mechanism was intentional. PMID- 8214831 TI - Pediatric head injuries: can clinical factors reliably predict an abnormality on computed tomography? AB - STUDY OBJECTIVE: To assess clinical features that might reliably predict the need for computed tomography (CT) imaging in pediatric head trauma. DESIGN/SETTING/TYPE OF PARTICIPANT: Prospective cohort of 324 head CT scans performed on 322 consecutive trauma patients at an urban children's hospital. RESULTS: Sixty-two percent of patients were male. The mean age was 7.1 years (10 days to 20.6 years); half were less than 5 years of age. The two most frequent mechanisms of injury were falls (32%) and motor vehicle accidents (25%). Abnormalities were detected in 74 scans. Intracranial injuries were apparent in 39 patients (12%); 16 had a concomitant fracture. An isolated cranial abnormality was observed on 35 scans (11%). Loss of consciousness, amnesia for the event, a Glasgow Coma Scale (GCS) of less than 15, and the presence of a neurologic deficit were more common in children with intracranial injury (P < .05). Vomiting, seizures, and headache were not discriminating clinical features. No single characteristic consistently identified the children with an intracranial injury. Of the 195 children who were neurologically intact (GCS, 15) at the time of presentation, 11 (5%) had evidence of intracranial pathology on CT scan. CONCLUSION: This study demonstrates a poor correlation between the clinical symptoms of significant traumatic brain injury and findings on CT. PMID- 8214832 TI - Routine screening of Halloween candy: helpful or hazardous? AB - STUDY OBJECTIVES: To determine the frequency of radiopaque items found in radiologic screening of Halloween candy and to determine the possibility of missing a small item. DESIGN: Prospective observational study on Halloween night, 1992. Data were collected from area medical centers that were screening Halloween candy. The ability to detect small sharp items was tested at five centers. SETTING: Five hospitals and three immediate care centers. PARTICIPANTS: Four hundred fifty-four bags of candy were screened. RESULTS: No unknown radiopaque items were discovered. One of five centers tested for accuracy failed to detect a small radiopaque item. Only one hospital required parents to sign a waiver of liability. The immediate care centers recorded patients' names; the other hospitals kept no record of the names of children whose bags were screened. No physicians viewed the radiographs or fluoroscopy. CONCLUSION: The routine radiologic screening of Halloween candy has an extremely low yield in detecting radiopaque items. PMID- 8214833 TI - Accuracy of bar codes versus handwriting for recording trauma resuscitation events. AB - STUDY OBJECTIVES: To compare the accuracy of computerized bar code data entry with conventional handwritten data entry during videotaped trauma resuscitations. SETTING: Laboratory; video simulation. TYPE OF PARTICIPANTS: Twenty-four emergency nurses. DESIGN: The nurses viewed videotapes of four different major trauma resuscitations during a single session. Each nurse recorded resuscitation events by handwritten entry in two cases and by bar code entry in another two. A computerized bar code system was designed specifically for contemporaneous charting of rapidly occurring events during trauma resuscitations. The handwritten and bar-coded records then were compared with a master list of events, and the number of entry errors were counted. Errors were defined as "omissions" (failing to record an event), "commissions" (recording an event that did not occur), or "inaccuracies" (errors in recording details of an event). ANALYSIS: Differences in the number of entry errors between the two recording methods were compared using unpaired t-tests. Differences in the number of errors after adjusting for the different nurses, different case being viewed, and order of viewing were analyzed using balanced analysis of variance techniques. P < .05 was considered significant. MAIN RESULTS: The mean +/- SEM number of total errors per record for bar codes was 2.63 +/- 0.24 compared with 4.48 +/- 0.30 for handwriting (P < .0001). The mean number of omissions per record for bar codes was 2.25 +/- 0.21 compared with 3.65 +/- 0.27 for handwriting (P = .0001). The mean number of inaccuracies per record for bar codes was 0.38 +/- 0.10 compared with 0.83 +/- 0.12 for handwriting (P = .0038). There were no commission-type errors. CONCLUSION: Computerized bar code data entry of trauma resuscitation events had significantly fewer entry errors than handwritten data entry in a laboratory setting. Potential advantages of bar code data entry include keyless data entry, automatic time-stamping, standardization of documentation, legibility of the medical record, and "point-of-care" data capture. PMID- 8214834 TI - Rapid transfusion of packed red blood cells: effects of dilution, pressure, and catheter size. AB - STUDY OBJECTIVE: To examine flow rates and quantify red blood cell (RBC) destruction using various catheter sizes, pressures, and dilutions in the transfusion of packed RBCs. DESIGN: Study equipment was identical to that used in clinical practice. Laboratory tests consisting of plasma free hemoglobin, hematocrit, RBC count, and plasma potassium were used to assess RBC destruction. Statistical analysis was performed using the two-tailed Student's t-test. Statistical significance was considered to be .05. INTERVENTION: Packed RBCs were transfused in vitro through 16-, 18-, 20-, and 22-gauge catheters using no pressure, 150 mm Hg, and 300 mm Hg pressure as well as dilutions of 0, 100, and 250 mL normal saline. OUTCOME MEASURES: Flow rates in milliliters per minute were recorded for all combinations. The extent of RBC destruction was estimated using RBC count, hematocrit, plasma free hemoglobin, and serum potassium. RESULTS: Increases in flow rates of tenfold simply by diluting the units with 250 mL normal saline and sevenfold with the application of a pressure device were seen at all catheter sizes. The combination of both dilution and pressure increased flow rates 33-fold, varying between 70 and 300 mL/min for 22- and 16-gauge catheters, respectively. No significant difference in RBC destruction was seen among the four catheter sizes. CONCLUSION: Flow rates of packed RBCs sufficient for volume resuscitation can be achieved using 20- and 22-gauge catheters without evidence of increased RBC destruction. When it is impossible to obtain large-bore venous access or when such access would necessitate a delay of five to ten minutes, smaller catheters used in conjunction with dilution, pressure, or both should be considered. PMID- 8214835 TI - Nonoperative management of blunt abdominal trauma: the role of sequential diagnostic peritoneal lavage, computed tomography, and angiography. AB - STUDY OBJECTIVE: To determine the usefulness of sequential nonoperative diagnostic studies in the evaluation and treatment of stable patients after blunt abdominal trauma. DESIGN AND SETTING: Retrospective review of a prospective treatment plan in a large urban Level I trauma center. PARTICIPANTS: Fifty-two patients deemed stable after initial evaluation following blunt abdominal trauma. INTERVENTIONS: Patients with a positive diagnostic peritoneal lavage for red blood cells underwent abdominal computed tomography (CT) scanning. If CT demonstrated a visceral injury, it was followed by diagnostic angiography. Attempts were made to treat on-going bleeding by transcatheter embolization. RESULTS: Fifteen patients had negative CT scans and were successfully observed. In the other 37 patients, CT identified 17 liver, 16 splenic, and eight kidney injuries; eight extra-peritoneal bleeds; and one mesenteric hematoma. Six of these patients were observed. Thirty underwent diagnostic angiograms. Twelve had no active bleeding, and all were observed successfully. Seventeen underwent successful embolization of the bleeding site(s). One had injuries not controllable by embolization and required exploration. Six patients required laparotomy later in their course, but none had intra-abdominal bleeding or a missed intestinal injury. Despite being performed after diagnostic peritoneal lavage, CT missed only two injuries. There was one main complication, delayed recognition of a diaphragmatic injury. Three patients died, two from multiple organ failure and one from a pulmonary embolus; none was believed to be related to this technique. With our algorithm, 45 patients (86%) were spared laparotomy. CONCLUSION: Diagnostic peritoneal lavage and CT are complementary when evaluating blunt abdominal trauma. Diagnostic peritoneal lavage is an effective screening tool. CT may be reserved for stable patients with a positive diagnostic peritoneal lavage to specify the organs injured. Bleeding often may be treated by embolization, limiting the rate of surgery. PMID- 8214836 TI - Splatter during jet irrigation cleansing of a wound model: a comparison of three inexpensive devices. AB - STUDY OBJECTIVE: Pressurized jet irrigation is commonly used to cleanse traumatic wounds but results in splatter of blood, a biohazard. Three inexpensive irrigation devices were compared to assess the degree of splatter produced: a 1.25-in. 18-gauge angiocath, an Irrijet Irrigation System with a 12.7-cm splash shield, and a Zerowet Splashield held directly against the wound (Zerowet-C) and held 4 to 10 cm from the wound, an incorrect technique (Zerowet-I). DESIGN: A standard laceration was created in pieces of beef. This wound model was placed 1 m from the floor. Paper grid sheets were placed on the irrigator's face and chest. Six grid sheets were suspended at the 9:00, 12:00, and 3:00 positions 1 m from the wound model and 1 and 1.5 m from the floor to simulate exposure to nearby individuals. Two grid sheets were placed flat on the floor, at the 10:30 and 1:30 positions, 1 m from the base of the wound model stand. The study area was contained in a 3 x 2 x 2 m plastic sheet enclosure to prevent air drafts. INTERVENTION: Ten irrigations were performed with the angiocath, Irrijet, Zerowet I, and Zerowet-C. Each run used 200 mL methylene blue solution delivered with a 50-mL syringe by one-hand pressure. The methylene blue splatter on each of the grids was counted by size (diameter, less than 1 mm, more than 1 mm and less than 5 mm, more than 5 mm and less than 10 mm, and more than 10 mm). RESULTS: There was significantly less splatter onto the irrigator's face and chest with Irrijet, Zerowet-I, and Zerowet-C. No facial splatter occurred with Zerowet-C. There was significantly less splatter at the 9:00 and 12:00 positions at both heights, and on the floor with Irrijet, Zerowet-I, and Zerowet-C. Less significant splatter difference was noted at the 3:00 position. CONCLUSION: Irrijet, Zerowet-I, and Zerowet-C were superior to the angiocath in preventing splatter during this wound model irrigation. The correct use of Zerowet (Zerowet-C) was particularly effective in preventing splatter onto the irrigator's face. PMID- 8214837 TI - Prognostic value of the emergency department cardiogram for in-hospital complications of acute myocardial infarction [corrected]. AB - STUDY OBJECTIVE: To identify patients who are admitted from the emergency department with chest discomfort who are at low risk for life-threatening complications. DESIGN: Retrospective chart review. SETTING: A 450-bed military medical center providing active duty and military beneficiaries. TYPE OF PARTICIPANTS: Six hundred twenty-one patients admitted to an ICU from the ED with the chief compliant of chest discomfort. MEASUREMENTS AND MAIN RESULTS: Study participants were placed into low- and high-risk groups based on clinical criteria and ECGs. The groups were compared with respect to occurrence of life threatening complications during the hospital course. Three of the 262 patients in the low-risk group experienced life-threatening events; two died. Twenty-nine of the 224 high-risk patients experienced life-threatening events; 17 died . Results were statistically evaluated using Fisher's exact test. Significance was achieved at a value of P < .01. CONCLUSION: Patients who meet low-risk group criteria have a low likelihood of immediate life-threatening events and could be admitted to an intermediate care unit. PMID- 8214838 TI - Emergency intubation with the Combitube: comparison with the endotracheal airway. AB - STUDY OBJECTIVE: To evaluate the safety and effectiveness of the Combitude as used by ICU nurses under medical supervision compared with endotracheal airway established by ICU physicians during CPR. DESIGN: Prospective study of ICU patients over a seven-month period. SETTING: Medical ICU. PARTICIPANTS: Thirty seven patients suffering from cardiac arrest. INTERVENTIONS: Emergency intubation with either the Combitube by nurses or the endotracheal airway by physicians and subsequent mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Evaluation of blood gases after 20 minutes of mechanical ventilation. Intubation time was shorter for the Combitube (P < .001). Blood gases for each device showed comparable results; PaO2 was slightly higher during ventilation with the Combitube (P < .001). CONCLUSION: The Combitube as used by ICU nurses was as effective as establishment of the endotracheal airway by intensivists during CPR. The Combitube may be used whenever endotracheal intubation cannot be performed immediately. PMID- 8214839 TI - Beliefs and practices of emergency medicine faculty and residents regarding professional interactions with the biomedical industry. AB - STUDY OBJECTIVES: To examine emergency medicine resident training and understanding of general bioethics and resident and faculty attitudes and behavior regarding professional interactions with the biomedical industry. DESIGN: Two companion questionnaire surveys. SETTING: Annual resident in-service examination and written director survey with telephone follow-up. PARTICIPANTS: Emergency medicine residents and program directors. INTERVENTIONS: chi 2 analysis was used for questions involving relationships among variables with dichotomous or categorical response. An analysis of variance or Pearson Product Moment Correlation was calculated for questions with continuous variables. MEASUREMENTS AND MAIN RESULTS: The surveys were completed by 1,385 of 1,836 (75%) residents and 80 of 81 (99%) residency directors. On average, residents receive eight hours of bioethical instruction per year but believe that they need 12 hours per year. Seventy-five percent of residents believe that company representatives sometimes cross ethical boundaries. The amount of resident understanding of bioethical concepts correlated with the number of hours of bioethics training they received. A sensitivity to bioethical conflicts index was correlated with the residents' behavior. CONCLUSION: There is wide variation in beliefs and practices regarding the interaction between emergency medicine residents and directors and the biomedical industry. Our results suggest that residents need training regarding conflicts of interest, accepted standards of practice, and dealing with potential conflicts with the biomedical industry. PMID- 8214840 TI - Nonoperative management of blunt abdominal trauma: time for a practice guideline? PMID- 8214841 TI - A trauma center for the United Kingdom. AB - In July 1991, a pilot trauma center was established in the United Kingdom as part of a government-funded evaluation of trauma services. The North Staffordshire Hospital is at the center of a trauma system that serves 2 million people. This system involves the five surrounding hospitals and the ambulance service. Key developments have been the provision of a consultant trauma team leader in the center 24 hours a day, closer networking of all the hospitals, and an expansion of the paramedic training program. Two comparator sites have been identified and are also being studied. The results of this three-year experiment are being evaluated independently and by the trauma research group of Keele University. Whatever the outcome, the project will have a significant influence on the future development of trauma care in the United Kingdom. PMID- 8214842 TI - Myth of the dangerous sternal fracture. AB - STUDY OBJECTIVE: To look at the hospital course and the outcome of patients with an isolated sternal fracture. DESIGN: Retrospective analysis of hospital records. SETTING: A large urban Level I trauma center. TYPE OF PARTICIPANT: Blunt trauma patients with an isolated sternal fracture. Patients with other chest radiograph abnormalities were excluded, as were those with abnormal admission ECGs. MEASUREMENTS AND MAIN RESULTS: Thirty-one patients with an isolated sternal fracture were identified. No patient developed new ECG changes or arrhythmias during the hospital stay. Cardiac enzymes were elevated in one patient (3.2%). No patient had any adverse cardiopulmonary outcome attributable to the sternal fracture. CONCLUSION: The outcome of patients with an isolated sternal fracture and a normal ECG is very good. Routine admission and cardiac monitoring do not appear to be warranted in this subset of patients with a sternal fracture. PMID- 8214843 TI - Pharmaceutical representatives and emergency medicine residents: a national survey. AB - STUDY OBJECTIVES: To determine the extent and diversity of involvement of pharmaceutical representatives in emergency medicine residency programs and to assess chief residents' beliefs and attitudes concerning this activity. DESIGN AND PARTICIPANTS: A multi-item survey with cover letter was mailed to the chief resident at each of the 87 Accreditation Council on Graduate Medical Education approved emergency medicine residency programs in the United States at the time of study conception. MEASUREMENTS AND MAIN RESULTS: Eighty-three percent (72 of 87) of the questionnaires were returned. Ninety-three percent (66 of 71) of responders reported the involvement of pharmaceutical representatives in their emergency medicine residency. The most frequent activities (90%, 63 of 70) were to distribute small gifts (pens, notepads) and to provide meals during department functions such as journal clubs (80%, 56 of 70). Only 32 of 70 responding chief residents (46%) were aware of any established guidelines in their institution or residency program concerning relationships with pharmaceutical representatives, and 14 respondents (20%) believed that accepting gifts from pharmaceutical companies could affect their own prescribing habits. A few stated that pharmaceutical representative-sponsored educational functions were inappropriate. CONCLUSION: The interaction of pharmaceutical representatives with emergency medicine residents and residencies is widespread. More than 50% of the institutions supporting emergency medicine residency programs have no formal guidelines with regard to the interaction of their residents with pharmaceutical representatives or their guidelines are not known to the person most responsible for approval and arrangement of the pharmaceutical representative interaction- the emergency medicine chief resident. While most chief residents believed that accepting small gifts was reasonable, they also believed that accepting gifts valued at $100 or more and pharmaceutical representative sponsorship of trips was inappropriate. PMID- 8214844 TI - Prehospital delay interval for patients who use emergency medical services: the effect of heart-related medical conditions and demographic variables. AB - STUDY OBJECTIVE: To investigate the effect of heart-related medical conditions and demographic variables on patients' tendency to delay contacting emergency medical services for symptoms of acute myocardial infarction. TYPE OF PARTICIPANTS: A sample of 2,947 patients with acute myocardial infarction but no cardiac arrest, transported by paramedics to the coronary care units of 19 hospitals in King County, Washington, between January 1988 and April 1991. MEASUREMENTS: Patient record abstracts contained information on medical history, age, gender, delay interval, and means of transportation. RESULTS: Multiple regression analyses showed that prehospital delay interval was significantly greater for individuals who were older and female and who had a history of angina, congestive heart failure, or diabetes. CONCLUSION: It is important to investigate further how people interpret and evaluate their symptoms in light of other medical conditions. It is also critical to find out why women delay longer than men and why older individuals delay longer than younger people before they contact emergency medical services. Interventions need to be developed that are targeted at populations at risk for delaying use of emergency medical services for acute myocardial infarction symptoms. These interventions must legitimize the use of emergency medical services and encourage patients to act quickly when confronted with acute myocardial infarction symptoms. PMID- 8214845 TI - Evolving concepts in pediatric bacterial meningitis--Part I: Pathophysiology and diagnosis. PMID- 8214846 TI - Evolving concepts in pediatric bacterial meningitis--Part II: Current management and therapeutic research. PMID- 8214847 TI - Severe hypernatremic dehydration and hyperkalemia in an infant with gastroenteritis secondary to rotavirus. AB - A case of severe hypernatremic dehydration (sodium, 191 mmol/L) with associated severe hyperkalemia (potassium, 11.2 mmol/L) and hyperosmolality (502 mOsm/kg) is described in a 3-month-old infant secondary to acute infection with rotavirus. The patient was managed with i.v. fluid resuscitation in conjunction with intracranial pressure monitoring and was discharged well and without any permanent sequelae. Review of the literature reveals the case described to be the most profound example of hypernatremic dehydration with a favorable outcome reported from diarrheal illness. Strategies for management of hypernatremic dehydration are discussed. PMID- 8214848 TI - Polymyalgia rheumatica and giant cell arteritis in emergency department patients. AB - Elderly patients with undiagnosed polymyalgia rheumatica and giant cell arteritis are not uncommon, and they may present to the emergency department with nonspecific physical complaints. We describe the cases of two patients who had the "typical" constellation of symptoms. It is important that emergency physicians consider the diagnosis and provide appropriate testing, therapy, and follow-up. PMID- 8214849 TI - Discharging heroin overdose patients after observation. PMID- 8214850 TI - Provision of medical care at sea. PMID- 8214851 TI - Meperidine and ketorolac in the treatment of painful sickle cell crisis. PMID- 8214852 TI - Animal research--laudable principles or room for improvement? PMID- 8214853 TI - Predicting survival from out-of-hospital cardiac arrest: a graphic model. AB - STUDY OBJECTIVE: To develop a graphic model that describes survival from sudden out-of-hospital cardiac arrest as a function of time intervals to critical prehospital interventions. PARTICIPANTS: From a cardiac arrest surveillance system in place since 1976 in King County, Washington, we selected 1,667 cardiac arrest patients with a high likelihood of survival: they had underlying heart disease, were in ventricular fibrillation, and had arrested before arrival of emergency medical services (EMS) personnel. METHODS: For each patient, we obtained the time intervals from collapse to CPR, to first defibrillatory shock, and to initiation of advanced cardiac life support (ACLS). RESULTS: A multiple linear regression model fitting the data gave the following equation: survival rate = 67%-2.3% per minute to CPR-1.1% per minute to defibrillation-2.1% per minute to ACLS, which was significant at P < .001. The first term, 67%, represents the survival rate if all three interventions were to occur immediately on collapse. Without treatment (CPR, defibrillatory shock, or definitive care), the decline in survival rate is the sum of the three coefficients, or 5.5% per minute. Survival rates predicted by the model for given EMS response times approximated published observed rates for EMS systems in which paramedics respond with or without emergency medical technicians. CONCLUSION: The model is useful in planning community EMS programs, comparing EMS systems, and showing how different arrival times within a system affect survival rate. PMID- 8214854 TI - Prolonged resuscitation efforts for cardiac arrest patients who cannot be resuscitated at the scene: who is likely to benefit? AB - STUDY OBJECTIVE: To determine who may benefit from prolonged resuscitation efforts after therapy by emergency medical services system (EMS) personnel has failed to restore vital signs. DESIGN: Retrospective chart review. TYPE OF PARTICIPANTS: Two hundred sixteen consecutive adult patients with out-of-hospital cardiac arrest who were admitted to the emergency department without vital signs. METHODS: Identification of prehospital resuscitation data, therapy in the ED, hospital course, and final outcome. RESULTS: Thirty-nine patients (18.1%) were resuscitated successfully. The odds ratio of successful resuscitation in the ED for the patients with ventricular fibrillation at the scene versus those with asystole or electromechanical dissociation was 3.4 (95% confidence interval, 1.5, 7.9). All patients with asystole or electromechanical dissociation, either at the scene or in the ED, died (95% confidence interval, 0, 4.3). CONCLUSION: Prolonged resuscitation efforts in the ED for patients with asystole or electromechanical dissociation usually are futile after previous efforts by the EMS personnel have failed to restore vital signs. Transportation to the hospital may not be indicated. However, for patients with persistent ventricular fibrillation, transport is indicated. PMID- 8214855 TI - Prehospital cardiac arrest treated by urban first-responders: profile of patient response and prediction of outcome by ventricular fibrillation waveform. AB - STUDY OBJECTIVES: To determine the speed and characteristics of patient response to urban first-responder defibrillation and to determine whether amplitude of ventricular fibrillation (VF) can predict outcome in these patients. TYPE OF PARTICIPANTS: All adult patients in prehospital VF treated by fire department first-responders (265). DESIGN AND INTERVENTIONS: A prospective observational study occurring between February 1, 1989, and January 1, 1991. Patients were defibrillated according to advanced cardiac life support and first-responder protocols. ECG and time data were recorded digitally. MAIN RESULTS: Sixty-five percent of patients converted from VF to a more stable rhythm at least once during first-responder monitoring. Fifty-four percent of converted patients refibrillated at least once, and 42% of all stable conversions occurred after at least one episode of refibrillation. Seventy percent of all refibrillations occurred less than six minutes after the defibrillator was turned on, and 23% occurred after more than ten minutes. The proportion of stable conversions decreased from 30% on first conversion to 2% on fourth conversion. With each successive conversion the interval to refibrillation grew shorter, and development of a pulse or blood pressure became less likely. Presence of blood pressure or pulse after conversion had a sensitivity for hospital discharge of 54% and a specificity of 98%. Maximum VF amplitude before countershock was highly predictive of postshock rhythm, stable conversion in the field, time interval before refibrillation, inpatient admission, and hospital discharge. VF amplitude was unrelated to response interval or interval to defibrillation but was positively related to bystander CPR. Logistic regression identified VF amplitude as the most important predictor of hospital discharge; traditional variables such as response interval and bystander CPR were not predictive once amplitude had been accounted for. Changes in VF amplitude during the course of resuscitation efforts were frequent and also predictive of outcome. CONCLUSION: Patients in VF who were treated by early countershock refibrillated much more frequently than previously reported. Refibrillations occur both early and late. Initial VF maximum amplitude is strongly predictive of outcome. Future reports of VF cardiac arrest should control for this previously neglected variable. Increased amplitude of VF during repeated refibrillation episodes is associated with increased hospital discharge, so future studies of advanced cardiac life support interventions should explore changes in VF amplitude as an outcome variable. PMID- 8214856 TI - Emergency vehicle intervals versus collapse-to-CPR and collapse-to-defibrillation intervals: monitoring emergency medical services system performance in sudden cardiac arrest. AB - STUDY OBJECTIVE: To compare emergency vehicle response intervals with collapse-to intervention intervals to determine which of these system data better correlated with survival after prehospital sudden cardiac arrest. STUDY DESIGN: A 22-month case series, collected prospectively, of out-of-hospital cardiac arrests. Times of collapse, dispatch, scene arrival, CPR, and initial defibrillation were determined from dispatch records, recordings of arrest events, interviews with bystanders, and hospital records. SETTING: Southwestern city (population, 400,000; area, 390 km2) with a two-tiered basic life support-advanced life support emergency medical services system. Emergency medical technician firefighters without electrical defibrillation capability comprised the first response tier; firefighter-paramedics were the second tier. PATIENTS: One hundred eighteen cases of witnessed, out-of-hospital cardiac arrest in adults with initial ventricular fibrillation. MAIN OUTCOME MEASURES: Survival was defined as a patient who was discharged alive from the hospital. RESULTS: Eighteen of 118 patients (15%) survived. Survivors did not differ significantly from nonsurvivors in age, sex, or basic life support or advanced life support response intervals. Survivors had significantly (P < .05) shorter intervals from collapse to CPR (1.7 versus 5.2 minutes) and to defibrillation (7.4 versus 9.5 minutes). CONCLUSION: Collapse-to-intervention intervals, not emergency vehicle response intervals, should be used to characterize emergency medical services system performance in the treatment of sudden cardiac death. PMID- 8214857 TI - Inter-rater agreement of paramedic rhythm labeling. AB - STUDY HYPOTHESIS: Substantial inter-rater agreement is present in the labeling by paramedics of ventricular fibrillation and asystolic rhythms. DESIGN: Prospective, cross-sectional study. TYPE OF PARTICIPANTS: One hundred five practicing paramedics from nonvolunteer agencies who are advanced cardiac life support certified. METHODS: Five static cardiac arrest rhythm strips, classified by Cummins' average peak amplitude method, were arranged into five different orders of presentation and placed into five booklets. The paramedics were instructed to label each rhythm ventricular fibrillation or asystole based on rhythm recognition, not on treatment plan. RESULTS: The overall kappa value for labeling the five rhythms was .63, indicating a moderate degree of inter-rater agreement. However, as the rhythm's amplitude decreased, the amount of inter rater agreement also decreased. When the amplitude was approximately 1 mm, agreement was no different than chance; the proportion of paramedics labeling the rhythm ventricular fibrillation was .46 (95% confidence interval, .36, .56). Only a flat line (0 mm) demonstrated perfect inter-rater agreement, with no paramedic labeling the rhythm ventricular fibrillation. CONCLUSION: Inter-rater agreement of ventricular fibrillation rhythm labeling by paramedics in this emergency medical services system was amplitude dependent. An analysis of ventricular fibrillation rhythm data that does not address the degree of inter-rater agreement of rhythm labeling cannot ensure uniform reporting of out-of-hospital cardiac arrest data. PMID- 8214858 TI - Emergency medical services priority dispatch. AB - STUDY OBJECTIVE: To test the ability of a locally designed priority dispatch system to safely exclude the need for advanced life support (ALS). DESIGN: Retrospective review of emergency medical services (EMS) incident records to determine how often the lone dispatch of basic life support (BLS) units, staffed with basic emergency medical technicians, subsequently required or involved ALS care. SETTING: A large centralized municipal EMS system with a tiered ALS/BLS ambulance response. All BLS units carry automated defibrillators. MEASUREMENTS: Consecutive EMS records (35,075) were reviewed by computerized search for ALS procedures. Records indicating ALS procedures were tabulated and then manually reviewed for the nature of and probable indication for the ALS intervention. INTERVENTION: Brief sequences of computer-stored questions that help dispatchers identify (or exclude) signs and symptoms indicating the need for ALS. RESULTS: The dispatch triage system spared ALS units from initial dispatch in 14,100 of the EMS incidents (40.2%), increasing their availability and use for more serious calls. Among these 14,100 cases, only 41 patients (0.3%) later received drugs such as nitroglycerin and naloxone; another 27 patients (0.2%) received resuscitative interventions such as epinephrine or defibrillation. Furthermore, on closer analysis, the immediate presence of a paramedic might have provided a true potential for advantage in outcome for only five or six patients (less than 0.04 of the 14,100 BLS dispatches). Meanwhile, many important operational, fiscal, and cost-effective patient care benefits were realized with this system. CONCLUSION: A computer-aided dispatch triage algorithm can facilitate improvements in both EMS system operations and prehospital patient care by safely and reliably identifying EMS incidents requiring only BLS. PMID- 8214859 TI - Role of the emergency medical services system in regionwide health monitoring and referral. AB - The emergency medical services (EMS) system of the future has the opportunity to serve as a regional community health monitoring and referral system. Such a system would shift attention from care of the individual to cost-effective community health efforts using community resource integration, while emphasizing individual responsibility for health. This health care system model requires the establishment of a centralized monitoring agency, the "regional center." The regional center would coordinate the monitoring of regional EMS use and linkage of patients with essential health promotion and behavior change organizations. Many of these supporting organizations are in place but are functioning without the benefit of communitywide health monitoring or effective referral and follow up links with other resources. Coordination through the EMS system and a regional center would permit these resources to be used in an efficient and accountable fashion. We propose a model in which the EMS system could contribute to coordinated regional health monitoring and maintenance, timely and appropriate health care legislation and regulation, and high-impact health care education and intervention in the setting of self-destructive individual behavior. PMID- 8214860 TI - A simplified prehospital advance directive law: Arizona's approach. AB - Many of the approximately 400,000 deaths that occur outside of hospitals or chronic care facilities each year in the United States are not only expected but also welcomed as relief from terminal disease. However, patients who lack decision-making capacity cannot communicate to emergency medical services system and emergency department personnel their wish not to be the recipient of advanced life support procedures. Prehospital advance directives (PHAD) offer that opportunity. Arizona is only the fourth state to pass a PHAD statute and the first to simplify the law so it is interpreted easily by both providers and patients. PHAD laws need not be complex, either in their language or in their implementation requirements. Simple and easily understood statues and their resulting directives increase the likelihood that those most likely to need and use this directive will be able to comply with its provisions. Arizona's law addresses several controversial areas yet to be worked out by other states. Placing the PHAD in statute ensures that a statewide attempt will be made to comply with its provisions, and as a law it should be more permanent than advance directive protocols based on administrative fiat. Physicians in other states may want to follow Arizona's lead and employ a joint effort by their state's bar association, hospital association, and medical association to smooth the passage of similar legislation. All parties involved, however, must not seek a perfect statute. Arizona's experience suggests that legislators will need to strike a balance between the needs of the citizens and the fears of lawyers wary of any potential liability for the state or the emergency medical services system. PMID- 8214861 TI - A proposed model for a residency experience in mass gathering medicine: the United States Air Show. AB - STUDY OBJECTIVE: Mass gathering medicine is an increasingly important responsibility for emergency physicians. A formal experience in mass gathering medicine can introduce emergency medicine residents to this aspect of community medicine. DESIGN: Educational model based on field experience and retrospective chart review from 1981 through 1991. SETTING: The US Air Show is a summer event that attracts an average of 223,000 spectators annually. Medical care is provided by physicians, nurses, and technicians operating within an organized system of care. Emergency medicine resident physicians (first-, second-, and third-year) evaluate and treat patients appropriate for the resident's level of responsibility. Residents provide immediate medical control and are integrated into the event disaster plan. On-site attending physician supervision is available at all times. Didactic instruction and event orientation are integrated into the residency curriculum. Residents participate in the planning stages of the event. RESULTS: During the study period, 2,091 patients were seen. The most common presenting problems were heat illness (28%), blisters and scrapes (25%), headaches (23%), fractures and lacerations (9%), and eye injuries (5%). One hundred forty-eight patients (7%) required transportation to the hospital. Approximately 16 residents participate each year and treat an average of 13.7 patients during their four-hour shift. A resident training model for a mass gathering experience is proposed to include adequate crowd size to generate useful patient volumes; a regularly scheduled event; organized medical and disaster preparations meeting local or published standards; didactic instruction on history, principles, and current issues; on-site attending supervision; degree of responsibility appropriate for training level; participation in planning and organizing the event; and postevent debriefing. CONCLUSION: A residency experience and training program in mass gathering medicine can introduce the principles of planning and providing care for crowds attending large public events. PMID- 8214862 TI - Disaster assessment: the emergency health evaluation of a population affected by a disaster. AB - In the past decade, interest in the operational and epidemiologic aspects of disaster medicine has grown dramatically. State, local, and federal organizations have created vast emergency response networks capable of responding to disasters, while hospitals have developed extensive disaster plans to address mass casualty situations. Increasingly, the US armed forces have used both their ability to mobilize quickly and their medical expertise to provide humanitarian assistance rapidly during natural and man-made disasters. However, the critical component of any disaster response is the early conduct of a proper assessment to identify urgent needs and to determine relief priorities for an affected population. Unfortunately, because this component of disaster management has not kept pace with other developments in emergency response and technology, relief efforts often are inappropriate, delayed, or ineffective, thus contributing to increased morbidity and mortality. Therefore, improvements in disaster assessment remain the most pressing need in the field of disaster medicine. PMID- 8214863 TI - Analysis of medical treatment at a field hospital following Hurricane Andrew, 1992. AB - STUDY OBJECTIVE: To determine what medical care was required of a special operations response team by a community devastated by a major hurricane. STUDY DESIGN: Retrospective analysis of 1,544 patient encounter forms generated at a field hospital set up in Homestead, Florida, after Hurricane Andrew in August 1992 and staffed by the special operations response team from Forsyth County, North Carolina. TYPE OF PARTICIPANTS: All persons presenting for treatment. RESULTS: One thousand two hundred three adult patients and 336 pediatric patients were seen by the special operations response team. Only five of the injuries treated were due directly to the hurricane, whereas 285 of the treated injuries were sustained during clean-up activities. Most of the care provided was routine medical care denied the citizens due to the loss of their physicians' offices and clinics. Supplies of tetanus toxoid, antibiotics, and insulin were depleted in 24 hours. Resupplying these items and acquiring other medication to refill prescriptions constituted a pressing problem. CONCLUSION: The primary function of medical personnel responding to an area hit by a major hurricane will be to provide general medical care. Any trauma encountered will be primarily due to clean-up activities and not due to the hurricane itself. Responding medical personnel should plan on providing their own food and water for the first 72 hours and be well stocked with antibiotics, tetanus toxoid, and insulin. PMID- 8214864 TI - Emergency department immunization of the elderly with pneumococcal and influenza vaccines. AB - STUDY OBJECTIVE: To determine the feasibility of immunizing unvaccinated elderly patients with influenza and pneumococcal vaccines in the emergency department. PARTICIPANTS AND SETTING: A convenience sample of elderly patients presenting to an urban university-affiliated ED. DESIGN AND INTERVENTIONS: Elderly ED patients were asked about prior influenza and pneumococcal immunization. Nonimmunized patients were given information sheets, were informed of the changes for vaccination, and were asked if they desired immunization as part of their ED care. Those desiring immunization who lacked contraindications were immunized. RESULTS: One hundred thirty-three patients were enrolled. Eighty-two percent had not been immunized with pneumococcal vaccine; 62% of these nonimmunized patients stated they desired pneumococcal vaccination, and 58% were immunized. Sixty-three percent of the 133 patients had not received current influenza vaccine; 54% of these nonimmunized patients stated they desired influenza vaccine, and 50% were immunized. CONCLUSION: The majority of elderly ED patients are not immunized adequately with influenza and pneumococcal vaccines as recommended by the Centers for Disease Control and Prevention. Most elderly patients will accept immunization with these vaccines as part of their ED care. These vaccines can be delivered effectively to elderly patients in the ED. PMID- 8214865 TI - Relationship of clinical presentation to time to antibiotics for the emergency department management of suspected bacterial meningitis. AB - STUDY HYPOTHESIS: The acuity and specificity of the clinical presentation of bacterial meningitis are significantly associated with the time to antibiotic administration. DESIGN: Retrospective case series. SETTING: Seven hundred-bed university and 1,000-bed community hospital. PARTICIPANTS: One hundred twenty-two children and adults primarily evaluated in the emergency department and admitted with the diagnosis of suspected bacterial meningitis. METHODS: The ED chart was reviewed for demographic, historical, physical examination, and time data and sequence of interventions. In addition, we categorized patient presentations as "sick" or not and as "classic" or not based on the following predetermined definitions. A "sick" presentation was defined as at least two of the following: temperature of more than 40 C, lethargic or comatose mental status, hypotension, or tachycardia. A "classic" presentation was defined as temperature of more than 39 C and at least one of the following: nuchal rigidity, bulging fontanelle, or abnormal mental status. Association of clinical variables and management practices to time to antibiotics was analyzed by analysis of variance and regression. RESULTS: The geometric mean time from ED registration until antibiotic initiation was 2.7 hours (range, 0.5 to 18 hours). Clinical factors that were associated independently with less time to antibiotics (hours less, P value) were a history of vomiting (0.5 hour, P = .06), no history of headache (0.8 hour, P = .01), hypotension (1.0 hour, P = .02), a bulging fontanelle (0.9 hour, P = .01), and a "sick presentation" (0.5 hour, P = .06). Management scenarios in which antibiotics were not administered until after return of results of computed tomography head scan or laboratory cerebrospinal fluid analysis and the practice of initiation of antibiotics on the ward compared with in the ED were associated independently with even greater delays (1.7 to 1.8 hours, P < .0001). CONCLUSION: Certain clinical factors, particularly those associated with acute illness compared with those that suggest the specific diagnosis, are associated with less time to antibiotics. Management practices, such as the order of interventions and the site of initiation of antibiotic therapy, appear to be of much greater importance in predicting antibiotic timeliness and represent an area of potentially avoidable delay for the ED management of suspected bacterial meningitis. PMID- 8214866 TI - Safety of lumbar puncture in patients with hemophilia. AB - STUDY OBJECTIVE: To determine the safety of lumbar puncture in patients with hemophilia who are pretreated with clotting factor. DESIGN: Retrospective analysis of medical records between 1980 and 1990. SETTING: Three hospitals, each serving as a regional hemophilia center. PARTICIPANTS: Thirty-three patients with hemophilia A or B who received one or more lumbar puncture. INTERVENTION: All patients received replacement of deficient factor before the lumbar puncture. Serious post-lumbar puncture complications were defined as motor or sensory deficits, incontinence, or documented intraspinal hemorrhage. RESULTS: Thirty three patients with hemophilia A or B received a total of 52 lumbar punctures during the study period. Thirty of 33 patients (91%) had severe baseline factor deficiency, two (6%) had moderate deficiency, and one (3%) had mild deficiency. There were no serious complications reported as a result of the lumbar puncture. The 95% confidence interval for the risk of a serious complication was 0% to 5.8%. CONCLUSION: With adequate factor replacement, a lumbar puncture can be done safely in patients with hemophilia. PMID- 8214867 TI - The future role of emergency medical services systems in prevention. AB - Like all new health system reform proposals, the RC proposal is not perfect. It does, however, begin to raise many of the right questions. Asking the right questions is the first step in creating workable answers. Let us judge the RC approach, as John Kitzhaber, MD, suggests, when evaluating any new health plan by applying the following criterion: To what degree is it an improvement over the status quo? PMID- 8214868 TI - Medicaid managed care and emergency care. PMID- 8214869 TI - To live and die in Arizona. PMID- 8214870 TI - Disaster medical assistance teams: a key role. PMID- 8214871 TI - Selection of emergency medicine residents. AB - The selection of emergency medicine residents requires review of medical school performance and, usually, an interview in which applicants and program directors exchange important information. Computer technology is available to assist programs in the analysis of information about applicants. Ethnic diversity and minority recruitment should also be considered as 40% of all emergency medicine residencies have no minority residents. Suggestions for developing a valid, humane, and fair selection process are made. PMID- 8214872 TI - Avulsion of the internal mammary artery caused by blunt trauma. AB - Injury to the subclavian artery or its branches is uncommon after blunt trauma. We report a case of blunt thoracic trauma resulting in avulsion of the right internal mammary artery from its origin on the subclavian artery. This presented as an atypical mediastinal hematoma in a patient with multiple injuries. PMID- 8214873 TI - Bungee jumper's foot drop peroneal nerve palsy caused by bungee cord jumping. AB - Peroneal nerve injury is a common peripheral neuropathy from a variety of conditions and injuries. We encountered a case of peroneal nerve palsy in a professional bungee cord jumper. Review of the literature showed no previous report of this particular injury in bungee cord jumping. PMID- 8214874 TI - Simultaneous asymmetric bilateral traumatic hip dislocation. AB - A 25-year-old man presented to the emergency department with simultaneous right anterior and left posterior hip dislocations resulting from a motor vehicle accident. Simultaneous bilateral traumatic hip dislocation is an uncommon occurrence. More rare is asymmetric simultaneous bilateral hip dislocation, with only ten cases documented in the English-language literature. The importance of an anteroposterior pelvic radiograph after significant major trauma is emphasized. Several serious complications can be associated with this condition, so expeditious management in the ED is warranted. PMID- 8214875 TI - Jewels--the peanut butter kid and the girl with the rose. PMID- 8214876 TI - Whole-bowel irrigation for theophylline overdose. PMID- 8214877 TI - Whole-bowel irrigation for theophylline overdose. PMID- 8214878 TI - XAP--an alternative to cocaine for topical anesthesia. PMID- 8214879 TI - Scleral icterus may be unilateral. PMID- 8214880 TI - 911 access and trauma deaths: a complex association. PMID- 8214881 TI - 911 access and trauma deaths: a complex association. PMID- 8214882 TI - 911 access and trauma deaths: a complex association. PMID- 8214883 TI - Medical staff responsibility for emergency department patients. American College of Emergency Physicians. PMID- 8214884 TI - Evaluation of agar gel immunodiffusion and indirect fluorescent antibody assays as supplemental tests for dourine in equids. AB - The agar gel immunodiffusion (AGID) and indirect fluorescent antibody (IFA) assays were evaluated as supplemental tests to the complement-fixation (CF) test, the official US importation certification test for dourine in equids. The American stabilate (n = 10 animals) or the Canadian stabilate (n = 6 animals) of Trypanosoma equiperdum cultured in rat blood was administered by catheterization and infusion in the urogenital tract of 16 equids. To assess parasitemia and serologic responses by use of the CF, AGID, and IFA tests, a total of 787 serum and blood samples were obtained from equids before exposure and 3 times a week after exposure to T equiperdum. Results of the IFA and AGID tests were compared with the CF test results. The disease was diagnosed earlier by the IFA test than by the AGID test, regardless of antigen preparation or exposure group. The mean number of days between exposure and positive result by the CF and IFA tests was the same when either homologous or heterologous antigen was used in the IFA test. In general, the IFA test was more sensitive than the AGID test in diagnosing dourine, regardless of the antigen preparation used in the test or exposure group. Differences in test specificity were observed among both groups of exposed equids when either antigen was used (P < 0.05). The AGID test, using the American antigen, was more specific than the IFA test for sera from both groups of equids. When the Canadian antigen was used, the IFA test was a more specific test than the AGID test (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214885 TI - Serum osteocalcin concentration in horses treated with triamcinolone acetonide. AB - The effect of triamcinolone acetonide (0.09 mg/kg of body weight, IM) on serum osteocalcin concentration was studied. Two groups of horses were investigated and included clinically normal horses (group 1, n = 5) and horses with chronic obstructive pulmonary disease (group 2, n = 5). Before treatment, results of a t test did not reveal any significant difference in serum osteocalcin concentration between the 2 groups. After treatment, a significant (P < 0.05) decrease in serum osteocalcin concentration was observed for both groups. Osteocalcin concentration in individual horses reached a minimum by 24 to 48 hours after treatment. In both groups of horses, serum osteocalcin response to glucocorticoid administration was similar. In 7 of 10 horses, return to pretreatment values was observed after 28 days. Pretreatment values for the other 3 horses were reached between 62 and 150 days. PMID- 8214886 TI - Comparison of the properties and concentrations of the isoforms of retinol binding protein in animals and human beings. AB - We used size-exclusion high-performance liquid chromatography (HPLC) to investigate the properties of the 2 isoforms of Vitamin A-containing (holo) retinol-binding protein (RBP) in animals: the form that is bound to transthyretin (holo-TTR-RBP), and the form that does not bind to TTR (holo-free RBP). We also used radial immunodiffusion to measure immunologically active RBP (apo + holo RBP). We compared the isoforms of RBP in animals with those of human beings to determine which animal is the best model of human RBP. Size-exclusion HPLC detected holo-free and holo-TTR-RBP in every animal species studied. Apparent concentration of holo-TTR-RBP varied among species: that of rabbits and dogs >> that of apes, sheep, goats, monkeys, rhinoceroses, felids, rats, human beings, and deer > that of pigs, zebra, and bison > that of penguins. Dogs have unusual RBP chromatograms; they have high concentration of RBP, but also appear to transport much of their vitamin A on protein other than RBP. Human RBP antibody preparations could detect apo + holo RBP immunologic activity only in apes, monkeys, and felids. Apes and monkeys appeared to have complete cross-reactivity to human RBP antibodies. Felids may have substantial, but partial, cross reactivity. Apes and monkeys appear to be the most relevant animal models for study of human RBP transport. However, there is a need for less-expensive models. Further research is needed, but in the interim, rats or sheep may be satisfactory for some purposes. PMID- 8214887 TI - Histomorphometric analysis of the omasum of sheep during development. AB - Histomorphometric and scanning electron microscopic analyses were performed on 74 embryos and fetuses and 20 sheep (early postnatal to adult age). Histologic differentiation of the omasum took place at 33 days of fetal life, with the appearance of first-order laminae. Second-, third-, and fourth-order laminae appeared at 39, 50, and 59 days, respectively. Neutral mucopolysaccharides first appeared in epithelial cells at 46 days of fetal life, decreasing quantitatively until birth, before subsequently stabilizing in postnatal life. Acid mucopolysaccharides, mucins, and mucoid compounds were not detected. Growth curves and formulas were constructed for each tissue layer. Initial tests involved multiplicative (y = axb), exponential (y = EXP [a + bx]), linear (y = a + bx), and polynomial models (y = a + bx + cx2 + dx3). PMID- 8214888 TI - Hemostasis in cows with endotoxin-induced mastitis. AB - Hemostasis was evaluated in cows with experimentally induced endotoxemia and mastitis, caused by intramammary infusion of endotoxin (1 mg) derived from Escherichia coli. Hemostatic tests included prothrombin time; activated partial thromboplastin time; thrombin time; fibrinogen, fibrin(ogen) degradation products, and platelet concentrations; and antithrombin-III and plasminogen activities. Significant alterations were observed in the mean values of most analytes (prothrombin time was increased; thrombin time was increased with subsequent decrease; activated partial thromboplastin time, fibrinogen concentration, plasminogen activity, and platelet concentration were decreased; and antithrombin-III activity and fibrin(ogen) degradation products concentration were unchanged) at 1 or more postchallenge sample collection times (3, 12, or 24 hours) after endotoxin administration, compared with mean values obtained from samples prior to endotoxin administration. These data indicated activation of hemostatic mechanisms, initiated either directly by endotoxin or by inflammatory mediators released or produced in response to endotoxin infusion. PMID- 8214889 TI - Platelet, antithrombin, and fibrinolytic activities in taurine-deficient and taurine-replete cats. AB - Cats with cardiomyopathy, especially dilated cardiomyopathy associated with taurine deficiency, often develop systemic thrombi. To investigate the relation of taurine deficiency to formation and persistence of thrombi, cats were made taurine-deficient by consumption of a casein-based taurine-deficient diet, then were evaluated for anticoagulant and profibrinolytic activities and platelet function. The cats served as their own controls in the taurine-replete state; then, values were compared for the taurine-deficient state. Plasma (P < 0.01), blood (P < 0.05), and platelet (P < 0.05) taurine concentrations were decreased markedly after cats consumed the taurine-deficient diet for 6 weeks, compared with baseline concentrations before diet. Compared with the taurine-replete state, taurine deficiency induced significantly (P < 0.05) increased mean antithrombin III activity, no significant change in plasminogen and fibrinolytic activities, and similar clot retraction/lysis test results. Decreased (P < 0.01) adenosine diphosphate (ADP)-induced platelet aggregation and [14C]serotonin release, and slightly increased (P < 0.05) collagen-induced platelet [14C]serotonin release, but unchanged collagen-induced platelet aggregation were observed in taurine-deficient cats, compared with taurine-replete cats. Changes in antithrombin III activity most likely reflected hepatocellular acute-phase reaction, which indicates that taurine deficiency may induce a stress-responsive state. Results of platelet function testing indicate that taurine may modulate platelet responsiveness to physiologic agonists, but not in consistent manner. That platelets from the taurine-deficient cats had decreased responsiveness to ADP, but increased responsiveness to collagen is surprising, because irreversible aggregation is mediated by release of granule-associated ADP after sufficient initial stimulus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214890 TI - Variation of abscess formation in cattle after vaccination with a modified-live Pasteurella haemolytica vaccine. AB - During the spring of the first year of a vaccine study, 57 of 238 calves (24%), in which modified-live Pasteurella haemolytica vaccine (MLV) was injected twice, developed 1 or more abscesses. Abscesses were not observed after multiple visual examinations of 437 calves given killed P haemolytica bacterin or placebo injections of similar adjuvants used in the vaccine and bacterin. Calves that developed abscesses after the second injection of MLV weighed significantly (P < 0.05) less (on the basis of body weight adjusted for weaning weight) at the second injection than did those that did not develop abscesses. Compared with calves given MLV that did not develop observable abscesses, calves developing abscesses after the second injection of MLV weighed 11.0 and 14.2 kg less, respectively, at 56 days and 112 days after injection, and they had 11.0 kg less gain at 56 days after injection. Abscess prevalence tended to be highest on certain days or at certain locations used for cattle processing, and the prevalence of abscesses increased in cattle processed later on a given day. Abscesses were not observed in 2 other groups of similarly treated calves vaccinated in the autumn or in the subsequent spring. PMID- 8214891 TI - Vaccination of calves with orally administered aromatic-dependent Salmonella dublin. AB - Genetically altered stable nonreverting aromatic-dependent (aro-) Salmonella dublin, strain SL5631, was administered orally to healthy colostrum-fed calves as vaccine. Twenty-six calves were allotted to 4 groups. There were 2 experiments, each with a vaccinated and nonvaccinated control group. Skin testing with 0.1 ml of sonicated S dublin was performed 3 days prior to challenge exposure. The IgG and IgM titers to S dublin lipopolysaccharide (LPS) antigen were determined by ELISA on sera before initial vaccination and at 1.5 to 2 weeks after each vaccination. In experiment 1, six calves received a dose of 1.7 x 10(10) colony forming units (CFU) of aro-S dublin SL5631 orally at 2 and 4 weeks of age. After the first vaccination, 2 of 6 calves developed fever, but all 6 calves continued to have normal appetite and mental attitude. Adverse changes were not observed after the second vaccination. At the time of challenge exposure at 6 weeks of age, all 12 calves were seronegative for IgG and IgM LPS-specific antibodies, and the difference in percentage increase in skin test reaction at 48 hours was not significant. At 6 weeks of age, the 6 vaccinates and 6 controls were orally challenge-exposed with 1.5 x 10(11) CFU of virulent S dublin T2340. Protection from challenge was not evident, as 3 of 6 controls and 5 of 6 vaccinates died after challenge exposure. In experiment 2, eight calves received a dose of 5 x 10(11) CFU of aro-S dublin SL5631 orally at 2, 3.5, and 5 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214892 TI - Transmission of proliferative enteritis to swine by use of embryonating chicken eggs. AB - Embryonating eggs were inoculated with filtered porcine ileal mucosa containing intracellular curved rods (ICR) and incubated for 4 to 6 days. Three of 12 pigs given the eggs per os developed microscopic lesions of proliferative enteritis (PE). Nonchallenge-exposed control pigs did not develop lesions of PE. Four of six positive control pigs given ileal mucosa from pigs with PE also developed microscopic lesions of PE. All of the PE lesions were found in pigs necropsied 10 to 29 days after challenge exposure. None of the swine in the study had clinical signs or gross lesions of PE. Campylobacter spp were isolated from pigs with and without exposure to the ileal mucosa from pigs with PE. There was no relationship between Campylobacter spp isolation and development of lesions. Deoxyribonucleic acids extracted from embryonating chicken eggs injected with the equivalent of 0.5 mg of mucosal lesions and incubated for 4 days hybridized to a DNA probe specific for the ICR, whereas DNA extracted from 1.5 mg of mucosal homogenates of the same proliferative tissue did not hybridize with the same probe. Results of these experiments indicated that ICR injected into eggs remained infective for pigs and suggest replication of ICR in the first-passage eggs. PMID- 8214893 TI - Adherence of Mycoplasma hyopneumoniae to porcine ciliated respiratory tract cells. AB - Adherence of Mycoplasma hyopneumoniae to the mucosa of the distal portion of the respiratory tract of swine is an important initial event in development of mycoplasmal pneumonia. A suitable in vitro model of adherence would be useful for investigation of mycoplasmal and host cell factors involved in this process. We have developed an adherence assay, using suspensions of porcine respiratory tract ciliated epithelial cells and M hyopneumoniae. Tracheal epithelial cells, collected by use of cytologic brushes, were mixed with broth cultures of M hyopneumoniae and the mixtures were incubated, diluted, vortexed, and sedimented. Pellets were spread on glass slides, stained with a fluorescent antibody against M hyopneumoniae, and evaluated by fluorescent microscopy. Fluorescence was observed principally among cilia on the ciliated tufts of epithelial cells. Only a few organisms were observed adhering on the nonciliated parts of ciliated cells or on other cell types. When mycoplasmas were preincubated with low dilutions of serum from swine convalescing from M hyopneumoniae disease, attachment was partially inhibited (P < 0.05). Significant inhibition of attachment was not observed when organisms were preincubated with higher dilutions of convalescent serum, with purified IgG from hyperimmune serum against M hyopneumoniae, or with low dilutions of lung lavage fluids (from convalescent swine) that contained specific IgA antibodies against M hyopneumoniae. Preincubation of the organisms with periodate and trypsin abolished attachment and formaldehyde decreased it (P < 0.05), whereas a variety of carbohydrates had no effect on attachment. Preincubation with dextran sulfate, ammonium sulfate, magnesium sulfate, and methionine reduced attachment (P < 0.05). Treatment of cell-Mycoplasma mixtures with the hydrophobic bond-breaking agent tetramethylurea, or incubation in absence of salt, or at low temperature also reduced attachment (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214894 TI - Determination of hemagglutination-inhibition titers to influenza A virus in porcine sera by use of an enzyme-linked immunosorbent assay. AB - An ELISA-based method to estimate hemagglutination-inhibition (HI) titer was developed. Subtype specificity was obtained by using purified H1 and H3 hemagglutinin antigens. Using the linear relation that exists between ELISA and HI methods, regression lines for H1N1- and H3N2-monospecific porcine antisera were constructed. Approximation of actual HI titer could be obtained from insertion of ELISA values into the appropriate regression line. The HI estimations were within 50% of the actual measured HI value 84% of the time. In young pigs that had suckled immune sows, use of this ELISA revealed estimated HI titer > 320 at 2 and 4 weeks of age. After a typical farm outbreak of influenza A/swine (H1N1), estimated HI titers remain high for 4 to 6 months. Sub-type specific estimation of the distribution frequency of positive influenza A (H1N1 or H3N2) results for sera from swine in regional herds indicated that 31.3 and 7.4% of the swine tested were positive (HI > 41) for H1N1 and H3N2, respectively. From these observations, we conclude that in many circumstances, an ELISA-based HI estimation method could be used as a substitute for the HI test. PMID- 8214895 TI - Seroepidemiologic survey for adenovirus infection in lambs. AB - A serologic survey was conducted to determine the prevalence and seroconversion rates for ovine adenovirus (OAV) serotypes 1-4 and bovine adenovirus (BAV) serotypes 2, 3, and 7 in sheep in Iowa and in surrounding states. For 2 consecutive years, paired serum samples were obtained from 1- to 2-month-old lambs as they entered a ram test station and, again, 2 months later. Sera were tested for adenovirus antibodies by use of a microtitration serum virus neutralization test. At the time of entry, high prevalence of antibody (titer > or = 2) was detected to all tested adenoviruses except BAV-3. All adenoviruses were active in the ram test station both years, as indicated by > or = fourfold increase in adenovirus antibody titer (seroconversion) in some of the lambs. The prevalence and seroconversion rate for OAV-1 was 94.0 and 7.2%, respectively; for OAV-2, 98.6 and 15.1%; for OAV-3, 86.5 and 11.0%; for OAV-4, 98.4 and 13.2%; for BAV-2, 97.6 and 22.4%; for BAV-3, 11.4 and 3.8%; and for BAV-7, 81.6 and 4.5%. The results indicate that adenovirus infections were widespread in the sheep population and that the prevalence of active infection based on seroconversion rates was approximately 45%. PMID- 8214896 TI - Toxin production by Pasteurella multocida isolated from rabbits with atrophic rhinitis. AB - Naturally acquired turbinate atrophy in rabbits was associated with Pasteurella multocida infection. Several in vitro and in vivo studies were conducted to document toxin production from P multocida isolates and to determine the relation of toxin to atrophic rhinitis in rabbits. Ten isolates of P multocida serotype A:12 were obtained from adult New Zealand White rabbits with noninduced atrophic rhinitis. Specific-pathogen-free rabbits inoculated intranasally with isolates of P multocida developed rhinitis and turbinate atrophy. However, inoculation with filtrates of the same bacteria failed to induce turbinate atrophy. Cytotoxicity was observed in assays, using bovine embryonic turbinate cell cultures with extracts of P multocida, but not in agar overlay cytotoxicity assays, using bovine embryonic turbinate, bovine embryonic lung, or Vero cell cultures, or in a sandwich ELISA, using monoclonal antibodies to purified P multocida toxin. Thus, turbinate atrophy was experimentally reproduced in rabbits with isolates of P multocida, but toxin was only detected in vitro by cell culture assay of P multocida extracts. PMID- 8214897 TI - Effects of shipping, handling, adrenocorticotropic hormone, and epinephrine on alpha-tocopherol content of bovine blood. AB - In 2 studies, plasma, erythrocyte, and neutrophil alpha-tocopherol concentrations were monitored in beef cattle after shipping, handling, and sample collection. On the basis of alpha-tocopherol results, an additional 2 studies were designed to measure the effects of administration of adrenocorticotropic hormone (ACTH) and epinephrine on the alpha-tocopherol concentration in the aforementioned blood constituents and on creatine kinase (CK) activity in Holstein calves. In the first of these studies, 15 beef cattle that had recently arrived at the feedlot consumed feed supplemented daily with 1,000 IU of dl-alpha-tocopheryl acetate. Values for initial blood samples indicated that CK activity was high. Although plasma alpha-tocopherol concentration indicated that vitamin supplementation was adequate, RBC and neutrophil alpha-tocopherol values were generally nondetectable. After 4 weeks of supplementation, plasma alpha-tocopherol concentration increased (P < 0.05), and neutrophil and RBC alpha-tocopherol values became measurable in most of the cattle. In the second study, 6 beef heifers had decreased (P < 0.05) plasma, RBC, and neutrophil alpha-tocopherol values after multiple periods of handling and blood sample collection. In the third and fourth studies, 10 tamed Holstein heifer calves, 5 of which were administered ACTH and epinephrine to simulate stress effects on blood alpha tocopherol concentrations and CK activity. In study 3, the vitamin E-adequate heifers had increased blood CK (P < 0.001) activity and cortisol (P < 0.01) concentration, and decreased (P < 0.05) neutrophil alpha-tocopherol concentration after hormone injections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214898 TI - Abomasal interstitial fluid-to-blood concentration gradient of pepsinogen in calves with type-1 and type-2 ostertagiosis. AB - Pepsinogen and protein concentrations were determined in blood samples, collected from the left gastroepiploic artery and vein, and in abomasal lymph from 15 steers naturally infected with Ostertagia ostertagi and 4 uninfected steers. In steers with type-1 ostertagiosis, the concentration gradient between the mucosal interstitium and the blood alone could account for higher than normal serum pepsinogen concentrations. High interstitial pepsinogen concentrations may have resulted from increased epithelial permeability or increased pepsinogen production and secretion. However, in steers with type-2 ostertagiosis, the concentration gradient could not entirely account for the high serum pepsinogen concentrations, suggesting that capillary permeability or surface area may have been altered. Lymphatic uptake contributed pepsinogen to the blood in all infected steers. PMID- 8214899 TI - Consequences of dose-dependent immunosuppression by progesterone on parasitic worm burdens in lambs. AB - Eighteen female lambs with prior exposure to Haemonchus contortus infections were ovariectomized and assigned to 1 of 3 replacement regimens: 0, 25, or 250 mg of progesterone/d delivered IM. After 3 weeks of hormonal treatment, all lambs were inoculated with 100,000 infective larvae of H contortus. After 8 weeks of hormonal treatment, a blastogenic assay was performed on blood lymphocyte populations, and the abomasum from each lamb was obtained for larval and adult worm recoveries of H contortus. Lambs of the 25 mg of progesterone group had significantly (P < 0.05) reduced blastogenic response to concanavalin A and greater adult and larval populations, compared with controls. Lambs of the 250 mg of progesterone group had worm burdens and lymphocyte blastogenesis values intermediate between those of the other treatment groups. PMID- 8214900 TI - Treatment of experimentally induced trichinosis in dogs and cats. AB - Studies were undertaken to determine the efficacy of milbemycin oxime against the enteric adult stages of Trichinella spiralis and of albendazole against the muscle stage larvae in experimentally infected dogs and cats. Specific-pathogen free Beagle pups (n = 6) and domestic shorthair kittens (n = 6) were inoculated with 7,500 first-stage larvae of Trichinella spiralis. Physical examination (including collection of blood and fecal samples) was performed weekly. During the first week after inoculation, all animals had mild gastrointestinal tract disturbances, but stages of T spiralis were not observed in the feces. Beginning on postinoculation day (PID) 10, 3 pups and 3 kittens were treated with milbemycin oxime (1.25 mg/kg of body weight, PO, q 12 h) for 10 days. Muscle biopsy specimens were taken from dogs and cats on PID 26 and 29, respectively. Mean numbers of larvae per gram of muscle were 30.3 in the control and 37.7 in the treated dogs. Mean numbers of larvae per gram of muscle in the control and treated cats were 318.7 and 89.3, respectively. Two dogs and 2 cats were removed from the study at that time. The remaining animals, 2 each of the control and milbemycin oxime-treated animals, were given albendazole (50 mg/kg, PO, q 12 h) for 7 days starting at PID 31 and 34 in dogs and cats, respectively. Muscle biopsy specimens were again taken at PID 46 and 49, for dogs and cats, respectively; mean numbers of larvae recovered from muscle were 0.6 for dogs and 13.5 for cats. PMID- 8214901 TI - Evaluation of bacterins containing three predominant phage types of Salmonella enteritidis for prevention of infection in egg-laying chickens. AB - Six Salmonella enteritidis bacterin formulations differing in adjuvant content and whole-cell inactivation procedures were evaluated in egg-laying chickens. Chickens given S enteritidis bacterins containing modified Freund's incomplete adjuvant had greater humoral immune responses to S enteritidis than did birds given other bacterin formulations (P < 0.05). Better protection against infection by S enteritidis phage types 8, 13a, and 23 was obtained in birds vaccinated with bacterin 5. Bacterin 5 contained S enteritidis cells inactivated by 20% acetone and modified Freund's incomplete adjuvant. PMID- 8214902 TI - Effects of triamcinolone acetonide on pulmonary function and bronchoalveolar lavage cytologic features in horses with chronic obstructive pulmonary disease. AB - Effects of triamcinolone acetonide (TA) on pulmonary function, bronchoalveolar lavage cytologic features and serum cortisol concentration, were studied in 5 control horses and 5 horses with chronic obstructive pulmonary disease (COPD). In experiment 1, horses were brought in from pasture 3 weeks before administration of 1 injection of TA (0.09 mg/kg of body weight, IM), and were stabled in dusty conditions throughout the experimental period. Measurements of respiratory rate (f), tidal volume, minute ventilation, expiratory-to-inspiratory time ratio, maximal change in transpulmonary pressure (delta PL), pulmonary resistance (RL), and dynamic compliance (Cdyn) were obtained during quiet breathing, immediately before (baseline) and 1, 2, 3, 5, and 9 weeks after administration of TA. Pulmonary airway cells were collected by bronchoalveolar lavage while horses were at pasture, at baseline, and 2, 5, and 9 weeks after TA administration. Serum cortisol concentration was measured before and after adrenocortical stimulation with 100 IU of adrenocorticotropic hormone, 1 week prior to TA administration, and 4 and 8 weeks thereafter. In experiment 2, 4 months after TA injection, pulmonary function measurements were repeated in all horses immediately before and 30 minutes after administration of atropine (0.015 mg/kg, IV), to evaluate the reversibility of airway obstruction. In experiment 1 at baseline, COPD affected horses had significantly (P < 0.05) higher values than did controls for f, delta PL, RL, and percentage of neutrophils, and had lower values for Cdyn and percentage of lymphocytes and macrophages. There was significant reductions in delta PL and RL, and increase in macrophage percentage after TA administration in COPD-affected horses only.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214903 TI - Cefazolin antibacterial activity and concentrations in serum and the surgical wound in dogs. AB - An antibiotic selected for surgical antimicrobial prophylaxis must be present in the surgical site throughout the operation in concentration sufficient to prevent growth of contaminating pathogens. The antimicrobial spectrum, minimal toxicity, and low cost of cefazolin make this first-generation cephalosporin a logical choice for antimicrobial prophylaxis in small animal surgical procedures in which the normal microbiologic flora of skin and gastrointestinal tract are the most likely pathogens. Pharmacokinetic variables of cefazolin were determined in serum and surgical wounds in dogs. Drug concentration in interstitial fluid of muscle biopsy specimens taken at random from wound surfaces and in postoperative wound fluid samples were determined. Effective surgical wound concentration of cefazolin was defined as 4 micrograms/ml, a concentration that inhibited the growth in vitro of 100% of staphylococcal and 80% of Escherichia coli clinical isolates. After IV and SC administrations, cefazolin equilibrated rapidly between serum and the surgical wound, and concentrations in the 2 sites decreased in parallel. With a bolus dose of 20 mg/kg of body weight given IV at the beginning of surgery and repeated by SC administration at 6 hours, cefazolin concentration in the surgical wound remained > 4 micrograms/ml for longer than 12 hours. PMID- 8214904 TI - Benzocaine-induced methemoglobinemia attributed to topical application of the anesthetic in several laboratory animal species. AB - In a screening study, a common benzocaine-containing anesthetic was topically applied to the following species: dogs (n = 11), domestic shorthair cats (n = 38), Long-Evans rats (n = 22), Sprague-Dawley rats (n = 11), ferrets (n = 6), rhesus monkeys (n = 10), cynomolgus monkeys (n = 10), owl monkeys (n = 10), New Zealand White rabbits (n = 18), miniature pigs (n = 9), ICR mice (n = 4), C3H mice (n = 4), and C57BL/10SnJ mice (n = 24). All animals, except mice and rats, received a 2-second spray to the mucous membranes of the nasopharynx for an estimated dose of 56 mg. A 2-second spray to rodents' oral mucous membranes delivered too great a volume of fluid for these animals; therefore, an equivalent dose was applied to the oral mucosa membranes by use of a 23-gauge needle and syringe. Initial (baseline) blood samples, as well as 4 blood samples taken every 15 minutes after drug application, were analyzed for methemoglobin (MHb), using an oximeter. Positive MHb response (> 3 SD above baseline) was seen in individuals of all groups. The study was repeated in dogs several months later to confirm low response. Response to benzocaine spray was observed in most animals tested, with response peaking between 15 and 30 minutes after dosing. Positive MHb response ranged from 3.5 to 38%, was detected in > 95% of individual animals, and ranged from 15 to 60 minutes after drug administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214905 TI - Evaluation of the effect of alfentanil on the minimum alveolar concentration of halothane in horses. AB - The effect of 3 plasma concentrations of alfentanil on the minimum alveolar concentration (MAC) of halothane in horses was evaluated. Five healthy geldings were anesthetized on 3 occasions, using halothane in oxygen administered through a mask. After induction of anesthesia, horses were instrumented for measurement of blood pressure, airway pressure, and end-tidal halothane concentrations. Blood samples, for measurement of pH and blood gas tensions, were taken from the facial artery. Positive pressure ventilation was begun, maintaining PaCO2 at 49.1 +/- 3.3 mm of Hg and airway pressure at 20 +/- 2 cm of H2O. The MAC was determined in triplicate, using a supramaximal electrical stimulus of the oral mucous membranes. Alfentanil infusion was then begun, using a computer-driven infusion pump to achieve and maintain 1 of 3 plasma concentrations of alfentanil. Starting at 30 minutes after the beginning of the infusion, MAC was redetermined in duplicate. Mean +/- SD measured plasma alfentanil concentration during the infusions were 94.8 +/- 29.0, 170.7 +/- 29.2 and 390.9 +/- 107.4 ng/ml. Significant changes in MAC were not observed for any concentration of alfentanil. Blood pressure was increased by infusion of alfentanil and was dose-related, but heart rate did not change. Pharmacokinetic variables of alfentanil were determined after its infusion and were not significantly different among the 3 doses. PMID- 8214906 TI - Influence of labor and neonatal hypoxia on sympathoadrenal activation and methionine enkephalin release in calves. AB - Labor and delivery stimulate increased release of catecholamines and endogenous opioid peptides in neonates. Catecholamines promote adaptation to the extrauterine environment after birth. Enkephalins are stored together with catecholamines in the adrenal medulla and have an inhibitory effect on catecholamine release. We investigated the influence of labor and neonatal hypoxia on epinephrine, norepinephrine, and met-enkephalin release in calves. Blood samples were taken from the umbilical artery before rupture of the umbilical cord and from the jugular vein repeatedly after birth. Highest plasma norepinephrine concentration was found in calves delivered at the end of gestation (term calves) before umbilical cord rupture. In calves delivered before the physiologic end of gestation (preterm calves), norepinephrine values increased after cord rupture, but remained lower than values in term calves. Epinephrine release followed a similar pattern, but norepinephrine was clearly predominant. In term calves, met-enkephalin values were significantly higher than values in preterm calves. In calves of both groups, met-enkephalin release increased after cord rupture. During birth, the increase in catecholamine release seems to take place earlier than that of enkephalins. Norepinephrine-dominated stimulation during expulsion of the calf might be followed by increasing enkephalinergic inhibition after cord rupture and onset of respiration. Reduced release of catecholamines and enkephalins in preterm calves may be connected with delayed adaptation to the extrauterine environment. PMID- 8214907 TI - Effect of phenylbutazone and repeated endotoxin administration on hemostasis in neonatal calves. AB - Twenty newborn Holstein calves were allotted at random to 4 groups: group A received 0.9% sterile saline solution; group B received phenylbutazone (5 mg/kg of body weight, IV) and 0.9% sterile saline solution; group C received progressively increasing doses of endotoxin (0.1 to 15 micrograms/kg); and group D received phenylbutazone and endotoxin similarly as did calves of groups B and C, respectively. Phenylbutazone was given once daily and saline solution or endotoxin were given every 8 hours for 5 days. Clinical variables--PCV, plasma total protein and fibrinogen concentrations, platelet count, prothrombin time, activated partial thromboplastin time, and fibrin degradation products concentration were measured at 24-hour intervals. Necropsy was performed on each calf. Phenylbutazone suppressed the clinical response to endotoxin challenge until large doses (7.5 to 15 micrograms/kg) were administered. Calves of groups C and D remained stable until they abruptly developed severe dyspnea necessitating euthanasia. Thrombocytopenia and leukopenia developed after the initial endotoxin dose. Prothrombin time was prolonged and PCV suddenly decreased at 96 hours. Necropsy revealed consistent lesions in the vascular endothelium and lungs. Phenylbutazone administration did not enhance or ameliorate endotoxin-induced hemostatic alterations or pathologic lesions. PMID- 8214908 TI - Reproducibility of urethral pressure profiles in clinically normal sexually intact female dogs by use of microtransducer catheters. AB - Urethral pressures profiles (UPP) obtained by use of microtransducer catheters were determined in 8 anestrous sexually intact female Beagles during general anesthesia. A UPP study consisted of 3 consecutive recordings, and 4 UPP studies were repeated at an interval of 5 days in each dog. Maximal urethral pressure (cm of H2O), bladder pressure (cm of H2O), and anatomic urethral length (cm) were recorded. Maximal urethral closure pressure (cm of H2O) was calculated. Mean +/- SD (for all measurements) maximal urethral closure pressure was 12.8 +/- 5.6 cm of H2O (range, 2.4 to 25.2 cm of H2O). Maximal urethral closure pressure was significantly (P < 0.05) decreased during the first recording period (11.4 +/- 5.8 cm of H2O), compared with the second (13.0 +/- 5.2 cm of H2O) or third (14.1 +/- 5.7 cm of H2O) recording periods within a UPP study (3 consecutive recordings). Mean maximal difference in urethral closure pressure during a single UPP study was 4.8 +/- 2.4 cm of H2O. Significant difference in maximal urethral closure pressure was not observed between studies. Mean (for all measurements) anatomic urethral length was 6.2 +/- 0.9 cm (4.1 to 7.8 cm). Anatomic urethral length was significantly (P < 0.05) less during the first recording period (6.1 +/- 0.9 cm), compared with values for the second and third periods (6.3 +/- 0.9 cm, 6.4 +/- 0.9 cm respectively). Anatomic urethral length for time 3 was significantly (P < 0.05) less than the value for time 1 (5.8 +/- 0.7 cm vs 6.6 +/ 0.8 cm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214909 TI - Effects of abdominal insufflation with nitrous oxide on cardiorespiratory measurements in spontaneously breathing isoflurane-anesthetized dogs. AB - Cardiorespiratory effects of abdominal insufflation were evaluated in 8 dogs during isoflurane anesthesia. Each dog was studied 3 times, in 1 of the following orders of insufflation pressures: 10-20-30, 20-30-10, 30-20-10, 10-30-20, 20-10 30, and 30-10-20 mm of Hg. Anesthesia was induced by use of a mask, dogs were intubated, and anesthesia was maintained by isoflurane in 100% oxygen. After instrumentation, baseline values were recorded (time 0), and the abdomen was insufflated with nitrous oxide. Data were recorded at 5, 10, 15, 20, 25, and 30 minutes after insufflation. The abdomen was then desufflated, with recording of data continuing at 35 and 40 minutes. Mean arterial pressure increased at 5 minutes during 20 mm of Hg insufflation pressure, and from 20 to 30 minutes during 30 mm of Hg pressure. Tidal volume decreased from 5 to 30 minutes during 10 and 20 mm of Hg pressures, and from 5 to 40 minutes during 30 mm of Hg pressure. Minute ventilation decreased at 10 and 20 minutes during 20 mm of Hg pressure. End-tidal CO2 concentration increased from 5 to 30 minutes during 20 and 30 mm of Hg pressure. The PaCO2 decreased at 40 minutes during 10 mm of Hg pressure, at 30 minutes during 20 mm of Hg pressure, and from 10 to 40 minutes during 30 mm of Hg pressure. Values for pH decreased from 10 to 30 minutes during 20 and 30 mm of Hg pressures. The PaO2 decreased from 20 to 40 minutes during 10 mm of Hg pressure, at 30 minutes during 20 mm of Hg pressure, and from 10 to 40 minutes during 30 mm of Hg pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214910 TI - Effect of intramuscularly administered polysulfated glycosaminoglycan on articular cartilage from equine joints injected with methylprednisolone acetate. AB - Intra-articularly administered, long-acting corticosteroids are a beneficial treatment for many equine joint disorders because they alleviate inflammation and signs of pain, but they also exert detrimental effects on the biochemical composition and morphologic features of articular cartilage. Chondroprotective drugs have been shown to mitigate some of the deleterious effects of intra articularly administered corticosteroids on articular cartilage of laboratory animals. Twenty-one ponies were assigned at random to receive 1 of 3 treatments in the right middle carpal joint. Group-1 ponies (n = 8) had methylprednisolone acetate (MPA; 0.2 mg/kg of body weight) and saline solution administered intra articularly and IM, respectively. Group-2 ponies (n = 9) received MPA (0.2 mg/kg) and polysulfated glycosaminoglycan (GAG; 2 mg/kg). Group-3 ponies (control; n = 4) had saline solution administered intra-articularly and IM. The corticosteroid or saline solution was injected into the right middle carpal joint on day 1. The IM administered polysulfated GAG or saline solution was administered at the same time, then was repeated every 3 days for 20 days. Ponies were euthanatized 21 days after initial injection by overdose of pentobarbital sodium. The cartilage of younger ponies was significantly (P < 0.05) more responsive to the proteoglycan-depleting effects of MPA. Ponies < 10 years old of groups 1 and 2 had significantly (P < 0.05) lower GAG content in the articular cartilage than did control ponies. Systemic treatment with polysulfated GAG did not result in a protective effect against proteoglycan loss from the articular cartilage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214911 TI - Inhibition of myelopoiesis by conditioned medium from cultured canine thymic cells exposed to estrogen. AB - Therapeutic doses of estrogens can cause fatal bone marrow damage in dogs, which are more sensitive than other species to these myelotoxic effects. Investigations with mice indicated that estrogens did not directly damage the bone marrow progenitor cells, but that the thymus responded to estrogen by producing a factor that inhibited bone marrow granulocyte-macrophage progenitor cell replication. A similar estrogen-induced myelopoiesis-inhibitory factor was produced by canine thymic cells in culture. This canine factor was more inhibitory to myelopoiesis than was the murine factor. Canine bone marrow progenitor cell growth was not significantly inhibited by direct estrogen treatment, which supported evidence for indirect thymus mediation of estrogen toxicity in vivo. Estrogen receptors were detected in canine nonlymphoid thymic cells by use of immunocytochemical staining. These findings indicate that the high estrogen sensitivity of dogs may relate to greater estrogen-induced myelopoiesis-inhibition by the thymus. PMID- 8214912 TI - Inhibition of myelopoiesis by serum from dogs exposed to estrogen. AB - The mechanism of estrogen-induced myelotoxicosis is unknown, although evidence indicates that estrogen does not directly damage the bone marrow granulocyte macrophage progenitor cells and that the thymus is a probable mediator of the bone marrow suppression. Estrogen-induced production of a myelopoiesis-inhibitory factor by canine thymic stromal cells in vitro has been observed. Then, presence of a myelopoiesis-inhibitory factor in canine serum was investigated immediately after estrogen administration in vivo. Maximal reduction in colony-forming units granulocyte/macrophage growth by sera from individual dogs varied. Individual dog sensitivity to estrogen-induced myelotoxicosis is seen clinically, and the cause is unknown. This serum factor could have a role in the eventual bone marrow hypoplasia seen in estrogen-treated dogs and is possibly the same factor produced by cultured thymic stromal cells exposed to estrogen. PMID- 8214913 TI - Twin, sibling, and adoption methods. Tests of evolutionary hypotheses. AB - Twin, sibling, and adoption studies have long been used by behavioral geneticists to identify genetic and environmental influences underlying human behavioral and physical variation. The full potential of these methodologies for unraveling the blend of biological, cultural, and experiential factors affecting human development has been insufficiently appreciated. The application of twin, sibling, and adoption designs for examining hypotheses generated by evolutionary theory is described. Potential contributions from a closer association between these disciplines are underlined. PMID- 8214914 TI - On sin versus sickness. A theory of perceived responsibility and social motivation. AB - Lack of effort as a cause of achievement failure evokes more punishment than does lack of ability. Perceptions of the controllability of these causes, inferences about personal responsibility, and affective reactions of sympathy and anger mediate between the causal perceptions of ability and effort and punishment responses. This general theory of social motivation explains some reactions to stigmatized persons as well as observations related to help giving, peer rejection, and aggression. The proposed conceptual system distinguishes the reactions to sin versus sickness. PMID- 8214915 TI - Political intervention in scientific peer review. Research on adolescent sexual behavior. AB - In 1991, the Secretary of Health and Human Services (HHS) rescinded funding for a survey of adolescent health risk-taking behavior. The decision overturned a series of scientific and ethical peer and administrative reviews of the research, which had been chosen in a competitive evaluation of proposals to advance knowledge about the prevention of acquired immunodeficiency syndrome (AIDS) and other diseases. The cancellation, coupled with congressional action to block similar research, left a gap in scientific data about adolescent health risk taking. The cancellation may also encourage the further use of political criteria in evaluating proposals for scientific research. Procedures for funding scientific research should be reformed to protect peer review from arbitrary political intervention. Through a discussion of this decision and its consequences for AIDS prevention research, principles that justify autonomous peer review are clarified and a reform that could strengthen it is discussed. PMID- 8214916 TI - Amiloride inhalation therapy in cystic fibrosis. Influence on ion content, hydration, and rheology of sputum. AB - Amiloride inhalation as treatment for cystic fibrosis (CF) lung disease has been shown in independent studies to increase mucus clearance by ciliary and/or cough action and to retard the decline in lung function. It is hypothesized that amiloride therapy decreases the excess sodium and water absorption that is a characteristic of CF airway epithelium and that it leads to an improvement in the rheologic properties of mucus favoring airway mucus clearance. The aim of this study was to investigate whether amiloride treatment (5 x 10(-3) M amiloride in one-third normal saline four times a day) would change sputum electrolyte composition in patients with CF after 25 wk of therapy as compared with placebo (one-third normal saline), and whether appropriate changes in sputum water content and rheologic properties would accompany any changes in electrolyte composition. Sputum samples were obtained from six patients with CF undergoing amiloride therapy, using the dental cotton protection technique to avoid salivary contamination. The samples were stored at -80 degrees C until analyzed. For electrolyte analyses an aliquot of the sputum (minimum, 30 mg) was analyzed with ion-selective electrodes for sodium and potassium, and a chloride meter was used to measure chloride content. Chronic (25-wk) amiloride therapy increased significantly the sputum sodium (94.8 +/- 16.4 to 121.4 +/- 15.4 mmol/L, p = 0.001) and chloride (64.4 +/- 11.8 to 77.2 +/- 8.0 mmol/L, p = 0.10) content when compared with 25 wk of saline treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214917 TI - Comparison of airway resistance and total respiratory system resistance in infants. AB - Airway resistance (Raw) can be measured throughout the respiratory cycle by whole body plethysmography. Total resistance of the respiratory system (Rrs) can be measured from the relaxed expiration that follows end inspiratory occlusion. The purpose of this study was to compare the two methods in normal infants and in infants with airway obstruction of different types and severity. Fifteen infants with essentially normal lungs aged 24.6 +/- 18.0 (SD) wk, nine infants with congenital stridor aged 36.0 +/- 17.3 wk, and eleven wheezy infants aged 20.1 +/- 11.3 wk had simultaneous measurements of Raw and Rrs. Rrs was similar to Raw both during inspiration and expiration in the normal infants, to all expiratory Raw in those with congenital stridor, and to all inspiratory and early expiratory Raw in the wheezy infants. Raw was markedly and significantly higher than Rrs during mid and late inspiration in infants with congenital stridor and during late expiration in the wheezy infants. We conclude that Rrs is a good estimate of Raw in normal infants and of early expiratory Raw in all infants. In infants with airway obstruction, Rrs does not reveal the dynamic changes in Raw during tidal breathing, nor can it differentiate between infants with upper and lower airway obstruction. PMID- 8214918 TI - A developmental study of the dose-response curve of the respiratory sensory reflex. AB - We have shown previously that inhalation of high concentration of CO2 (about 8%) inhibits breathing in preterm infants, presumably through an upper airway sensory reflex. To study the developmental aspects and the dose-response curve of this reflex, we studied eight preterm infants (body weight, 1.6 +/- 0.1 kg mean +/- SE; gestational age, 31 +/- 1 wk; postnatal age, 22 +/- 5 days) and eight term infants (body weight, 3.2 +/- 0.1 kg; gestational age, 39 +/- 1 wk; postnatal age, 8 +/- 6 days) using a flow-through system; eight adult subjects (weight, 67 +/- 5 kg; age, 30 +/- 4 yr) were studied during quiet sleep using a nasal mask. We gave 2, 4, 6, and 8% CO2 in 21+ O2 randomly for 20 to 30 s. A clear inhibition of breathing typically occurred during inhalation of 8% CO2 only in preterm infants, as reflected by the presence of an apnea of 11 +/- 1 s occurring at 7 +/ 2 s after the beginning of CO2 inhalation. Short apneas were occasionally observed with lower concentrations of CO2, but they were significantly fewer and shorter than with 8% CO2. No clear inhibition was observed in term infants or adult subjects, but pauses of 4 and 6 s were observed in the former group and a pause of 7 s was observed in the latter one. The associated changes in minute ventilation during inhalation of 2, 4, and 6% CO2 were not significantly different between the three groups. During inhalation of 8% CO2, minute ventilation decreased only in preterm infants (-26 +/- 10 compared with +32 +/- 10 in term infants and to +17 +/- 5% in adult subjects; p = 0.003 between groups).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214919 TI - Myotonia of the respiratory muscles in myotonic dystrophy. AB - Myotonic dystrophy is a muscle disorder in which there is a tendency to rapid shallow breathing and a reduced ventilatory response to chemical stimuli. Respiratory failure may occur when respiratory muscle weakness is not marked. One explanation proposed for these observations is that myotonia of the respiratory muscles reduces the compliance of the chest wall. However, direct electrical evidence of myotonia in the respiratory muscles with breathing is lacking. In 11 patients with myotonic dystrophy the scalene, sternocleidomastoid, a parasternal muscle, and a lateral intercostal muscle were studied using intramuscular bipolar wires. Five of the 11 patients had an elevated PaCO2. All patients had a FVC greater than 70% of predicted. Myotonia was sought with needle insertion, quiet tidal breathing, voluntary large breaths, and involuntary larger breaths with chemical stimulation. Two of the 11 patients demonstrated no myotonia. Myotonia on insertion of the needle was seen in four patients. Myotonia was rare in an isolated respiratory cycle during quiet breathing, and repetitive myotonia with consecutive breathing cycles was never noted. Voluntary big breaths produced myotonia in five patients, whereas chemically stimulated larger breaths produced myotonia in seven patients. In two of these seven patients, myotonic activity with consecutive respiratory cycles was seen at higher levels of ventilation. In conclusion, the rare occurrence of myotonia with tidal breathing would suggest myotonia in the muscles does not account for the respiratory failure and tachypneic breathing pattern found in myotonic dystrophy. Its occurrence at higher levels of ventilation may contribute to the reduced ventilatory response to chemical stimuli. PMID- 8214920 TI - Digital monitoring of sleep-disordered breathing using snoring sound and arterial oxygen saturation. AB - A new portable digital recorder (SNORESAT) that uses the sound of snoring and arterial oxygen saturation (SaO2) to monitor breathing abnormalities during sleep was constructed and compared in the laboratory with standard overnight polysomnography (PSG). The device digitally records sound from a transducer applied to the chest and SaO2 from a commercially available ear oximeter. A snore is identified when the moving time average of the sound exceeds a threshold voltage level longer than 0.26 s. The stored data are transferred to a personal computer for poststudy analysis. An analysis algorithm identifies a respiratory disturbance event when a quiet period of 10 to 120 s separates two snores and is associated with a fall in SaO2 exceeding 3%. The respiratory disturbance index (RDI), mean apnea duration, mean lowest SaO2, and number of desaturations > 3% are computed. A total of 129 referrals to the sleep apnea outpatient clinic underwent simultaneous all-night recording of PSG and SNORESAT. Using the computed RDI recorded by the SNORESAT, the sensitivity and specificity of the monitor in detecting sleep apnea syndrome (SAS) ranged between 84 and 90% and 95 and 98%, respectively, depending on the PSG value of RDI used to define SAS (range, > or = 7 to > or = 20 events/h). Using a PSG value of RDI > or = 10, or > or = 20 RD/h as the definition for SAS, the prevalence of SAS in the referral population was 45 and 31%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214921 TI - Theophylline improves gas exchange during rest, exercise, and sleep in severe chronic obstructive pulmonary disease. AB - The effects of theophylline on pulmonary function and gas exchange during rest, sleep, and exercise were assessed in 10 patients with severe but stable chronic obstructive pulmonary disease (COPD; median FEV1, 31% of predicted). The study was randomized, double blind, placebo controlled, and crossover in design, with each study period lasting 3 wk, and all other usual bronchodilator therapy was continued unchanged. All patients had detailed pulmonary function tests, in addition to exercise testing and overnight sleep studies by standard polysomnography. Theophylline significantly improved gas exchange during rest, exercise, and sleep. Awake resting arterial blood gases showed a higher PaO2 on theophylline (78 [53 to 93] mm Hg, median [range]) than placebo (72 [47 to 83] mm Hg; p < 0.01 by ANOVA), and PaCO2 was lower on theophylline (42 [38 to 54]) compared with placebo (45 [40 to 51], p < 0.05 by ANOVA). Arterial oxygen saturation (SaO2) was significantly higher on theophylline than placebo during exercise and sleep (p < 0.01), and transcutaneous CO2 was lower during sleep (p < 0.05). Theophylline also resulted in significantly improved pulmonary function and reduced trapped gas volume (p < 0.05). Exercise performance was no different during theophylline or placebo phases of the study. Sleep quality, however, was significantly impaired on theophylline. We conclude that theophylline has clinically significant benefits in patients with severe COPD. PMID- 8214922 TI - Intrinsic PEEP in patients with chronic obstructive pulmonary disease. Role of expiratory muscles. AB - Many patients with severe chronic obstructive pulmonary disease (COPD) contract the transversus abdominis (TA) muscle during expiration. The mechanical correlates of this contraction, however, are uncertain. In the present study, we have measured airflow, esophageal (Pes), and gastric (Pga) pressures, the anteroposterior (AP) diameter of the abdomen, and the electromyogram of the TA during resting breathing in 25 seated patients with severe COPD (FEV1 = 28 +/- 8% of predicted). Nine patients (Group I: FEV1 = 29 +/- 8% of predicted) in general had no TA activity during breathing, and 16 patients (Group II: FEV1 = 27 +/- 8% of predicted) had invariable phasic expiratory TA activity. In all patients of Group II, the decrease in abdomen AP diameter during expiration was associated with a gradual fall in Pga. In contrast, in 13 patients of Group II, the expiratory decrease in abdomen AP diameter was associated with a rise in Pga; this rise in Pga averaged 2.8 +/- 2.2 cm H2O. Furthermore, most patients had positive alveolar pressure at end-expiration, as shown by the time lag between the fall in Pes at the beginning of the inspiratory effort and the onset of inspiratory flow. However, whereas end-expiratory alveolar pressure averaged 2.4 +/- 2.2 cm H2O in Group II, it was only 0.8 +/- 0.6 cm H2O in Group I (p < 0.05). For the patient group as a whole, there was a close relationship between the rise in Pga during expiration and end-expiratory alveolar pressure (r = 0.87; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214924 TI - Role of atrial natriuretic factor in impaired sodium excretion of normocapnic and hypercapnic patients with chronic obstructive lung disease. AB - To investigate the mechanisms of sodium retention in patients with chronic obstructive lung disease (COLD), we examined the renal and hormonal responses to volume expansion with isotonic saline and to infusion of atrial natriuretic factor (ANF) in 10 hypercapnic (PaCO2 52 +/- 2 mm Hg) and 12 normocapnic patients (PaCO2 39 +/- 1 mm Hg). Sodium excreted within 4 h of loading (expressed as % sodium load) was 23.5 +/- 2.5% (p < 0.05) in normocapnic and 8.5 +/- 1.5% (p < 0.001) in hypercapnic patients, compared with 32.5 +/- 3.0% in 11 age-matched control subjects. Sodium excretion and renal blood flow correlated negatively with arterial PCO2 and positively with FEV1. Basal plasma ANF concentrations were 72 +/- 5 pg/ml in controls, 100 +/- 14 pg/ml in normocapnic patients, and 230 +/- 52 pg/ml in hypercapnic patients (p < 0.001). Plasma renin activity and aldosterone did not differ between groups. In response to volume expansion, plasma ANF increased in both normocapnic and controls (with a greater increase in normocapnic patients) but remained unchanged in hypercapnic patients. Exogenous ANF increased glomerular filtration rate, renal plasma flow, natriuresis, and diuresis in both groups of patients. Patients with COLD have depressed renal function that appears unrelated to activation of the renin-angiotensin aldosterone system. An increased secretory response of ANF to volume expansion may help to maintain volume homeostasis in normocapnic patients, while a blunted secretory response of ANF may contribute to sodium retention in hypercapnic patients. PMID- 8214923 TI - Chronic hypoxic pulmonary hypertension. Is thrombin involved? AB - Thrombin contracts vascular smooth muscle and stimulates its proliferation. Using a specific thrombin inhibitor, hirudin, we studied whether thrombin contributes to the pulmonary vasoconstriction and vascular proliferation that occurs in pulmonary hypertension. Hirudin was infused intravenously (0.2 mg/h/kg) by minipumps in nine rats during a 3-wk exposure to hypobaric hypoxia (HH). Vehicle (normal saline) was infused in eight hypoxic control (HC) and seven normoxic control (NC) rats. Sufficient hirudin delivery was confirmed by a failure of undiluted plasma from HH, but not from NC and HC, to clot in response to thrombin. When the plasma samples were diluted 1:10, the thrombin time was significantly prolonged in HH when compared with that in both NC and HC. Although hirudin slightly reduced mean pulmonary arterial pressure in open-chest rats, there was no significant difference between the hypoxic groups in total pulmonary resistance, right ventricle weight, morphologic remodeling of lung vessels, or the perfusion pressure-flow relationship in isolated lungs. Vasoconstrictor responses of isolated lungs to angiotensin II and acute hypoxic challenges were not affected by hirudin treatment. We conclude that hirudin, in a dose sufficient to reduce thrombin's catalytic effect on fibrinogen, does not significantly prevent the development of chronic hypoxic pulmonary hypertension. PMID- 8214925 TI - Erythromycin inhibits the production of elastase by Pseudomonas aeruginosa without affecting its proliferation in vitro. AB - Extracellular proteases from Pseudomonas aeruginosa play important roles in infections in the respiratory tract. The effect of erythromycin (EM), a macrolide antibiotic, on the production of elastase by P. aeruginosa was investigated in vitro and compared with the effect of other antibiotics. Thirty-four (94.4%) of thirty-six different strains produced detectable amounts of elastase determined by the gel diffusion method. The elastase production was inhibited completely by EM in 27 (79.4%) of 34 strains at some concentrations between 0.125 and 64 micrograms/ml. At 4 micrograms/ml or less, the elastase production was inhibited completely in four (11.8%) strains and more than 50% in the other 10 (29.4%). At 8 micrograms/ml or less, the elastase production was inhibited completely in 11 (32.4%) strains and more than 50% in the other nine (26.5%). The proliferation was partially inhibited at 32 and 64 micrograms/ml. Roxithromycin inhibited the elastase production at higher concentrations than EM without inhibiting the proliferation. Midecamycin and ampicillin did not inhibit the elastase production or the proliferation. Doxycycline and ticarcillin inhibited the elastase production and/or the proliferation at concentrations greater than 16 micrograms/ml. Although ofloxacin (OFLX) inhibited both the proliferation and the elastase production in parallel at low concentrations, there were six (16.7%) strains resistant to OFLX. Among them the elastase production was inhibited in five strains by EM. These results suggest that EM acts on P. aeruginosa to inhibit extracellular production of elastase without affecting the proliferation of the bacteria. PMID- 8214926 TI - Selective inhibition of the cutaneous late but not immediate allergic response to antigens by misoprostol, a PGE analog. Results of a double-blind, placebo controlled randomized study. AB - The objective of this study was to investigate the effect of misoprostol on allergen-induced cutaneous immediate- and late-phase allergic reactions in a double-blind placebo-controlled randomized study. We also studied the mechanism of antiallergic effects of misoprostol. A total of 16 dust mite-allergic patients received misoprostol (200 micrograms) or placebo and then had skin testing on 2 different days. The immediate- and late-phase skin response was monitored for 6 h. Skin biopsy was obtained from 5 selected donors at 5 h. In vitro studies included the effect of misoprostol on eosinophil chemotaxis, eosinophil survival, basophil histamine release, and cytokine production by lymphocytes. All subjects developed an immediate wheal reaction and a late-phase induration in response to dust mite allergens after taking placebo. Misoprostol selectively inhibited the late- but not the immediate-phase response (p < 0.05). Histologic studies revealed a trend toward a reduced number of inflammatory cells in the skin dermis after misoprostol treatment. Misoprostol significantly (p < 0.05) inhibited eosinophil chemotaxis and the production of granulocyte-macrophage colony stimulating factor by lymphocytes at concentrations > or = 10(-8) M. However, at significantly lower concentrations (> or = 10(-12) M) misoprostol blocked cytokine-stimulated eosinophil survival. Thus, misoprostol has potent antiallergic effects and blocks the cutaneous late-phase allergic inflammation. PMID- 8214927 TI - Neural cell adhesion molecule and prognosis of surgically resected lung cancer. AB - The prognostic significance of the expression of neural cell adhesion molecule (NCAM), a neuroendocrine antigen in lung cancer, was analyzed by an indirect immunoperoxidase method in 97 surgically treated patients. Reactivity of MOC-1 and S-L 11.14, both cluster-1 monoclonal antibodies directed against NCAM, was positive in all nine small-cell lung cancers and in 16 of 88 (18%) non-small-cell lung cancers. For the latter group, this expression demonstrated a phenotypic heterogeneity that was mainly observed in poorly differentiated squamous cell carcinomas and in stage N2 non-small-cell lung cancers. Patients with NCAM positive non-small-cell lung cancer proved to have a shorter survival than those with NCAM-negative disease. In Cox's model for multivariate analysis, nodal status and histology were the main independent determinants of prognosis. We therefore concluded that NCAM expression in non-small-cell lung cancer is correlated to nodal status and that it indicates a poor prognosis. These findings confirm that the diversification of lung cancer phenotype leads to tumor progression and brings a negative prognosis to surgically resected non-small-cell lung cancer. However, nodal status remains the most important prognostic variable, suggesting that NCAM expression is only one of numerous biological events that promote tumor progression. PMID- 8214928 TI - The predictive value of appearances on thin-section computed tomography in fibrosing alveolitis. AB - Fibrosing alveolitis, a condition characterized by a poor prognosis and a limited response to treatment, is readily identified by thin-section computed tomography (CT). Fibrotic and inflammatory histologic results, obtained at open lung biopsy, both have characteristic CT patterns. To evaluate whether CT could predict prognosis and response to therapy, we examined the CT appearances of 76 patients with lone cryptogenic fibrosing alveolitis and 66 patients with fibrosing alveolitis associated with systemic sclerosis. CT abnormalities were categorized as predominantly a ground-glass pattern (Grade 1), mixed (Grade 2), or predominantly a reticular pattern (Grade 3). In cryptogenic fibrosing alveolitis, 4-yr survival was highest in association with CT Grade 1 and higher with CT Grade 2 than with CT Grade 3, independent of the extent of abnormal lung on CT, duration of dyspnea, or severity of depression of DLCO or FVC, p < 0.001. A response to therapy in previously untreated cryptogenic fibrosing alveolitis was seen most frequently with CT Grade 1 and more frequently with CT Grade 2 than with CT Grade 3, p < 0.025. In systemic sclerosis, CT appearances were not predictive of 4-yr survival; a response to therapy was seen more frequently with CT Grade 2 (three of seven patients) than with CT Grade 3 (zero of six patients). These data have shown that CT appearances are of prognostic value in fibrosing alveolitis and that they are likely to play an increasing role in disease-staging in this condition. PMID- 8214929 TI - Tracheal sound spectra depend on body height. AB - Tracheal sounds originate from turbulent flow in upper and central airways. Turbulent flow characteristics are influenced by conduit dimensions. Because tracheal dimensions are a function of body height, we hypothesized that there should be a correlation between sound spectra and body length. We recorded tracheal sounds at standardized airflows in 21 healthy children 9.1 +/- 0.6 yr of age (mean +/- SE) and in 24 healthy adults 30.2 +/- 0.8 yr of age. A contact sensor was attached at the suprasternal notch of the sitting subject, and airflow was measured at the mouth with a calibrated pneumotachograph. Tracheal sounds were low-pass-filtered at 2.4 kHz and digitized at 10 kHz. A 2048 point FFT was applied at a successive 100-ms intervals, using a Hanning data window. Resulting spectra were normalized to a reference power of 0.1 (mV)2/5 Hz. We applied a gating algorithm to extract sounds at inspiratory flows of 1 L/s (+/- 10% tolerance), and we computed average power spectra from the collected samples. We calculated the average spectral power (Pavg), the quartile frequencies below which 25% (Q1), 50% (Q2), and 75% (Q3) of the power in the range of 50 to 2,000 Hz was contained, the spectral edge frequency (SE95) below which 95% of the power was found, and the frequency where spectral power rolled off sharply (Fcut).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214930 TI - Hypersensitivity pneumonitis and exposure to zirconium silicate in a young ceramic tile worker. AB - We describe a nonsmoking ceramic tile worker 25 yr of age who developed a worsening dry cough and dyspnea after 3.5 yr as a sorter and glazer of tiles. Open lung biopsy revealed an intense granulomatous interstitial pneumonia with mild fibrosis, compatible with hypersensitivity pneumonitis, and numerous very small birefringent crystals around the terminal airways and occasionally in granulomas. Pulmonary particle analysis revealed an inhaled dust burden nearly 100-fold the normal background level, mainly consisting of clay minerals and zirconium silicate. The patient had no history or clinical or laboratory findings suggesting any organic etiologic agent. A sarcoid granulomatosis type of chronic pulmonary hypersensitivity reaction is known after long-term exposure to zirconium, but this case demonstrates that zirconium can also cause an acute and fulminant allergic alveolitislike hypersensitivity reaction. PMID- 8214931 TI - Cryptogenic constrictive bronchiolitis. A clinicopathologic study. AB - Four women with a chronic respiratory illness characterized by chronic cough, dyspnea, mild to severe physiologic abnormalities, relatively normal chest radiographs, and lack of response to bronchodilators or prednisone were identified and prospectively evaluated. Constrictive bronchiolitis, defined as concentric narrowing of the bronchiolar lumen, mural scarring, smooth muscle hyperplasia, and mucus stasis, was the major histologic finding on open lung biopsy in all cases. Each presented with an illness clinically distinct from asthma, connective tissue disorders, occupational or environmental lung disease, bronchiectasis, diffuse panbronchiolitis, cystic fibrosis, and emphysema. None of the patients smoked cigarettes. None had clinical evidence of a recent viral lower respiratory tract infection. The physical examinations were normal except for rales heard on chest examination in two patients. Chest radiographs showed increased bronchovascular markings in three patients. Lung function was normal in one patient, two of the patients had a reduced diffusing capacity associated with moderate hypoxemia and an obstructive ventilatory defect, and one patient exhibited a mixture of restrictive and obstructive defects. None have experienced significant progression of their disease over 1 to 5 yr of follow-up. However, complete return to normal function did not occur. We hypothesize that patients with the constellation of findings described represent a distinct and definable clinicopathologic entity and further clarifies the spectrum of "small airways disease." Establishing the diagnosis appears important for prognostic and possibly therapeutic reasons. PMID- 8214933 TI - Training programs in adult pulmonary disease and critical care and training programs in pediatric pulmonary disease. 1993 editions. American Thoracic Society/American Lung Association. PMID- 8214932 TI - NHLBI workshop summary. Assessment of lung function and dysfunction in studies of infants and children. PMID- 8214934 TI - Partitioning of intrinsic PEEP. PMID- 8214935 TI - Respiratory control during exercise in patients with cardiovascular disease. PMID- 8214936 TI - Surfactant replacement therapy. New levels of understanding. PMID- 8214937 TI - Changes in exogenous surfactant in ventilated preterm lamb lungs. AB - Preterm lambs were treated with either a surfactant from bovine lung (Survanta) or three synthetic surfactants (Exosurf), a 69:22:9 mixture of dipalmitoylphosphatidylcholine, phosphatidylglycerol, and palmitic acid prepared by heat annealing (Lipid Mixture 1) or with glass beads (Lipid Mixture 2). After 5 h of ventilation, large and small aggregate surfactant fractions were isolated from alveolar washes by centrifugation. SP-A was used as an indicator for the association of endogenous surfactant components with the treatment surfactants. The large aggregate fraction from Survanta-treated lambs contained more SP-A than did the fractions from the lambs treated with the other surfactants (p < 0.05). The surfactants used to treat the sheep and the large aggregate surfactants from alveolar washes increased compliances when tested in surfactant-deficient, immature rabbits, relative to that in control animals. The large aggregate fractions in alveolar washes from lambs treated with Survanta, Lipid Mixture 1, and Lipid Mixture 2 improved compliances in the preterm rabbits to a greater extent than did the surfactants used to treat the lambs. The small aggregate fractions were inactive as surfactants. The function of exogenous surfactant can be improved after exposure to the preterm lung. The improvement may result from the association of exogenous surfactant with components of endogenous surfactant. PMID- 8214938 TI - 99mTc-DTPA clearance in preterm lambs. Effect of surfactant therapy and ventilation. AB - Surfactant therapy and high-frequency oscillatory ventilation (HFO) may minimize damage to the pulmonary epithelium of surfactant-deficient newborns. Using pulmonary clearance of insufflated, aerosolized 99mTc-DTPA (molecular weight 492) as an index of lung epithelial permeability, we examined the effects of 300 mg bovine lipid extract surfactant (S) administered at birth to preterm lambs ventilated by either HFO or conventional mechanical ventilation (CMV). Four groups of lambs, delivered by cesarean section at 129 to 133 days of gestation, were studied: (1) HFO + S, (2) CMV + S, (3) HFO, and (4) CMV. 99mTc-DTPA clearance was assessed at 2, 4, and 5.5 h after birth. Surfactant treatment improved oxygenation and lung pressure-volume relationships, with oxygenation best maintained by the combination of HFO + S. All groups had similar biexponential clearance curves at the three time points, however, and there was no significant difference in the mean rates of clearance (k) between the four groups at 2 h (k = 6.03 +/- 0.60 [SEM], 7.04 +/- 1.46, 5.67 +/- 0.91, and 7.23 +/ 0.97 %/min for Groups 1, 2, 3, and 4, respectively), 4 h (k = 6.95 +/- 0.77, 5.60 +/- 0.51, 6.39 +/- 0.64, and 6.78 +/- 1.71 %/min), and 5.5 h (k = 7.43 +/- 0.78, 6.08 +/- 0.80, 7.86 +/- 0.90, and 7.95 +/- 0.66 %/min). These data suggest that neither surfactant nor HFO significantly alters pulmonary epithelial permeability to a small radiolabeled molecule in preterm lambs. PMID- 8214939 TI - Airway occlusion pressure and breathing pattern as predictors of weaning outcome. AB - Airway occlusion pressure (P0.1) and the ratio of breathing frequency (f) to tidal volume (VT) (f/Vt) are good predictors of weaning outcome. However, the specificity of f/VT in predicting weaning success is relatively low. We postulated that the product of P0.1 and f/VT (P0.1*f/VT) would better predict weaning outcome than either variable alone. In 45 male patients, we prospectively evaluated P0.1*f/VT, P0.1, and f/VT in predicting weaning outcome. The threshold values of each variable were determined from published data. The sensitivity, specificity, and positive and negative predictive values in detecting weaning success, and the area under the receiver operating characteristic (ROC) curves were calculated. Ten (22%) of the 45 patients failed weaning. P0.1*f/VT yielded the highest specificity and positive and negative predictive values. P0.1*f/VT, P0.1, and f/VT were all highly sensitive (0.97); but they were less specific, 0.60 for P0.1*f/Vt and 0.40 for P0.1 and f/VT. The areas under the ROC curves for P0.1*f/VT, P0.1, and f/VT were not significantly different. We conclude that P0.1*f/VT has equivalent sensitivity as P0.1 and f/VT. P0.1 slightly improves the specificity of f/VT in predicting weaning success. PMID- 8214940 TI - Arteriovenous differences in PCO2 and pH are good indicators of critical hypoperfusion. AB - Recent reports have suggested that increases in venoarterial difference in PCO2 (VAPCO2) and arteriovenous difference in pH (AVpH) represent valuable markers of tissue hypoxia in shock states associated with low cardiac output. We compared the values of VAPCO2 and AVpH with that of blood lactate in their relationship to changes in O2 uptake (VO2) and O2 delivery (DO2) during an acute reduction in blood flow induced by cardiac tamponade. In 13 anesthetized and mechanically ventilated dogs, a catheter was inserted into the pericardium to inject saline and to measure the intrapericardial pressure. VO2 was derived from expired gas analysis. DO2 was calculated by the product of the thermodilution cardiac index and the arterial O2 content. The critical DO2 (DO2crit) was found at 9.9 +/- 1.8 ml/kg.min. VAPCO2 and AVpH, which were 7.1 +/- 4.6 mm Hg and 0.028 +/- 0.025 U, respectively, at baseline, progressively increased to reach 17.5 +/- 6.6 mm Hg and 0.114 +/- 0.054 U, respectively, at DO2crit (both p < 0.01). Below DO2crit they increased more dramatically. These changes were related to both arterial hypocapnia and mixed venous hypercapnia. CO2 excretion decreased from 5.8 +/- 2.0 ml/kg-min at baseline to 3.9 +/- 0.9 ml/kg.min at DO2crit (p < 0.01). End-tidal CO2 tension significantly fell below DO2crit. Lactate levels increased from 2.1 +/- 0.5 to 3.5 +/- 0.5 mmol/L at DO2crit (P < 0.01) and to 6.9 +/- 2.1 mmol/L (p < 0.01) at the end of the study. There was no statistically significant difference between the DO2crit calculated for VAPCO2, AVpH, lactate, or VO2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214941 TI - Delivery of ultrasonic nebulized aerosols to a lung model during mechanical ventilation. AB - Ultrasonic nebulizers may be particularly suitable for the administration of therapeutic aerosols to patients undergoing mechanical ventilation, but the amount of aerosol that reaches the patients' respiratory tract during ultrasonic nebulization has not been adequately studied. The delivery through an endotracheal tube of nebulized aerosols labeled with 99mTechnetium human serum albumin was therefore measured for five commercially available ultrasonic nebulizers using an in vitro model representing mechanical ventilation of an adult patient. Delivery of aerosol through the endotracheal tube ranged from 3.1 +/- 0.3% for Samsonic to 10.1 +/- 2.0% for Portasonic using 3 ml nebulizer solution. Increasing the volume of nebulizer solution to 18 ml (not possible for the Portasonic) increased delivery to 11.5 +/- 2.0 for the DP 100, 8.7 +/- 3.1 for Ultraneb, and 15.9 +/- 1.8% for Samsonic. Addition of a 600 ml aerosol storage chamber to the ventilator circuit increased delivery for the Samsonic (18 ml solution) to 22.3 +/- 5.0%. Aerosol delivery was also increased by reducing the respiratory rate and minute volume and by increasing the inspiratory time settings on the ventilator. These results confirm the potential value of ultrasonic nebulizers during mechanical ventilation and indicate that clinical trials in ventilated patients are warranted. PMID- 8214942 TI - Changes of pulmonary glucocorticoid receptor and phospholipase A2 in sheep with acute lung injury after high dose endotoxin infusion. AB - In a sheep model of acute lung injury induced by an Escherichia coli endotoxin (5 micrograms/kg) with chronic lung lymph fistula (n = 15), we measured the changes in glucocorticoid receptor (GCR) binding capacity in lung tissue by means of radioligand binding assay. The content of cortisol and the activity of phospholipase A2 (PLA2) were also measured. The results showed that the maximal binding capacity (Bmax) of GCR in lung cytoplasma decreased continuously 2 h (113 +/- 3 versus 66 +/- 2 fmol/mg protein, p < 0.01), 4 h (105 +/- 6 versus 52 +/- 3 fmol/mg protein, p < 0.01), and 6 h (105 +/- 5 versus 37 +/- 2 fmol/mg protein, p < 0.01) after endotoxin infusion. Its affinity decreased markedly (p < 0.05) at 6 h after the infusion. The contents of cortisol in plasma elevated at 0.5 h and remained at a high level until 4 h after the infusion. PLA2 activity rose from 97 +/- 25 to 188 +/- 12 U (p < 0.05), 99 +/- 13 to 285 +/- 25 U (p < 0.01), and 106 +/- 14 to 354 +/- 32 U (p < 0.01) at 2, 4, and 6 h after endotoxin infusion, respectively. There was a negative correlation between the Bmax of GCR and PLA2 activity (r = -0.87, p < 0.01). The findings indicate that there was a secondary GCR abnormality and a higher PLA2 activity during endotoxin-induced lung injury. The glucocorticoid hypofunction caused by reduced GCR binding capacity may accelerate the pathologic response of acute lung injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214943 TI - Amelioration of post-ischemic lung reperfusion injury by prostaglandin E1. AB - To reduce ischemia-reperfusion injury, a number of clinical lung transplant programs employ prostaglandin E1 (PGE1) or prostacyclin (PGI2) before donor lung flush and harvest. The effect of prostaglandins on the reperfusion component of this ischemia-reperfusion complex is unknown. We investigated the effect of PGE1 given only during the period of reperfusion, on ischemic lung injury in an in situ rabbit model. To examine the mechanisms involved, we measured pulmonary hemodynamics as well as myeloperoxidase, circulating platelet, and tumor necrosis factor (TNF) values. Two hours of warm ischemia of the left lung was produced in anesthetized New Zealand white rabbits. The animals were randomly allocated into four groups based on treatment received only during reperfusion: PGE1, PGI2, nitroprusside (NP), or no treatment (controls). After 2 h of reperfusion, PaO2 in the PGE1 group was significantly higher (423 +/- 52.7 mm Hg) than in all other groups (PGI2, 239 +/- 43.4, p < 0.05; NP, 146 +/- 14.2 p < 0.01; controls, 74 +/- 19.1 mm Hg, p < 0.01), despite similar pulmonary vascular resistance in the PGE1 and NP groups. Although lower than in the PGE1 group, PaO2 in the PGI2 group was still significantly higher than that in controls. Wet/dry lung weight ratios were significantly lower in the PGE1 and PGI2 groups (6.5 +/- 0.2 [p < 0.01] and 6.9 +/- 0.6 [p < 0.05], respectively, versus 8.2 +/- 0.1 in controls). There were no significant differences in plasma TNF levels, platelet sequestration across the lungs, or lung myeloperoxidase activity in the four groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214944 TI - Interleukin-8 production in patients undergoing cardiopulmonary bypass. The influence of pretreatment with methylprednisolone. AB - Pulmonary dysfunction caused by pulmonary neutrophil sequestration is a frequent postoperative complication in patients undergoing cardiopulmonary bypass (CPB) surgery. It is yet unclear whether treatment with corticosteroids in vivo in these patients can prevent complement-mediated neutrophil activation and sequestration in the lungs. Therefore, we conducted a prospective study in order to investigate whether methylprednisolone (MP) pretreatment (30 mg/kg) could influence the appearance of IL-8 (a recently discovered cytokine with potent neutrophil-chemotactic activity) in the peripheral circulation. We also studied the effects of MP pretreatment on the inflammatory parameters in the bronchoalveolar lavage (BAL) fluid 4 h postoperatively. Although peripheral neutropenia and the rise in IL-8 serum levels was less pronounced in MP-treated than in non-steroid-treated patients, there was no significant difference in albumin, total protein, concentrations of IL-8 and C3a, and the number of neutrophils in the BAL fluid between the two groups. However, when cultured in vitro, alveolar macrophages from patients treated with MP released significantly lower IL-8, both in basal conditions and after stimulation with lipopolysaccharide. Our results show that MP does not prevent (IL-8-mediated) pulmonary neutrophil infiltration after CPB, although it might affect certain aspects of the microvascular lung injury. PMID- 8214945 TI - Leukotriene B4 markedly elevated in the epithelial lining fluid of patients with cystic fibrosis. AB - Persistent neutrophil infiltration into the airways of patients with cystic fibrosis (CF) results in lung destruction. Eicosanoid lipid mediators, particularly leukotriene B4 (LTB4), may play a role in neutrophil influx and activation. We compared the eicosanoid content of epithelial lining fluid (ELF) obtained by bronchoalveolar lavage (BAL) from 17 patients with CF and 10 healthy subjects. LTB4 was the predominant eicosanoid in the CF airway (16.7 +/- 9.1 ng/ml ELF in CF versus 0.5 +/- 0.1 ng/ml ELF in healthy subjects). Prostaglandins (PG) and thromboxane (TX) were also elevated in CF (PGE2, 8.5 +/- 2.2; PGF2 alpha, 6.0 +/- 2.0; and TXB2, 14.0 +/- 3.0 ng/ml ELF) compared with healthy subjects (PGE2, 0.4 +/- 0.2; PGF2 alpha, 0.5 +/- 0.2; and TXB2, 1.2 +/- 0.4 ng/ml ELF). We also developed a protocol for the storage and subsequent analysis of BAL fluid that assures accurate and reproducible measurements of these eicosanoids. BAL samples stored for up to 8 months retain greater than 80% of their original eicosanoid content if the BAL fluid is immediately treated with methanol, concentrated, and stored at -70 degrees C without further purification. These data suggest that CF airways contain sufficient amounts of LTB4 both to recruit additional neutrophils into the airways and to stimulate neutrophils to release their injurious products. Therapies aimed at interfering with the production or action of LTB4 may be beneficial in CF and other lung diseases with a significant neutrophil response. PMID- 8214946 TI - The in vivo effect of tachykinins on airway mast cells of the rat. AB - The tachykinins substance P (SP) and neurokinin A (NKA) have been demonstrated in sensory airway nerves of animals and man and are thought to be neurotransmitters of local axon reflexes, generated by stimuli such as cigarette smoke, dust, histamine, and bradykinin. We previously showed that intravenous SP and NKA caused bronchoconstriction in anesthetized, mechanically ventilated rats. Pharmacologic studies suggested that this occurred by an indirect mechanism, probably mediated by acetylcholine and serotonin. In this study, we demonstrate that the bronchoconstriction caused by SP and NKA in Fisher 344 rats is accompanied by a dose-dependent release of histamine and serotonin in bronchoalveolar lavage (BAL) fluid. In rats depleted of mast cell mediators by pretreatment with compound 48/80, the effects of SP and NKA on lung resistance and serotonin in BAL fluid were abolished. Local instillation of NKA in the airways caused a significant dose-dependent increase in BAL histamine. After pretreatment with thiorphan, an inhibitor of neutral endopeptidase (NEP), the bronchoconstriction and the histamine and serotonin release in BAL fluid caused by SP and NKA were enhanced. After pretreatment with a combination of thiorphan and the angiotensin-converting enzyme inhibitor captopril, NKA and SP were almost equipotent in causing bronchoconstriction and serotonin release in the airways. This study indicates that mast cells are largely involved in the bronchoconstrictor effect of intravenously administered neurokinins in rats. As in the guinea pig, NEP is involved in the termination of the bronchoconstrictor effect of tachykinins. Moreover, NEP also affects the airway histamine and serotonin release caused by these tachykinins in the Fisher 344 rat. PMID- 8214947 TI - Effect of dexamethasone on airway inflammation and responsiveness after antigen challenge of the rat. AB - The purpose of this study was to examine the effects of dexamethasone on airway responsiveness and lung inflammation of rats at 8 h, 32 h, and 7 d after allergen challenge. Brown-Norway male rats, 7 to 8 wk old, were actively sensitized to ovalbumin (OA) and challenged 14 d later. The rats were divided into a control group (n = 31) and a test group (n = 34) that received dexamethasone (DEXA) (0.3 mg/kg intraperitoneally) 14 h and 2 h before saline or OA challenge. For challenge, rats were anesthetized with pentobarbital and intubated endotracheally. Aerosols of OA (5% wt/vol in saline) were administered for 5 min. Responsiveness to inhaled aerosols of methacholine and the total and differential leukocyte counts in the large airways (generations 0 to 5), small airways, and parenchyma isolated by tissue mincing and digestion were measured at 8 h, 32 h, and 7 d after OA challenge. The cellular influx into the airways and parenchyma was highest at 8 h and decreased progressively over 7 d. DEXA significantly inhibited the cellular influx after allergen challenge. At 8 h, cellular return from the large airways was 3.61 +/- 0.5 x 10(6) (controls) versus 1.0 +/- 0.2 x 10(6) (DEXA), and from the small airways and parenchyma was 31.7 +/- 2.8 x 10(6) (controls) versus 21.9 +/- 2.9 x 10(6) (DEXA) (p < 0.05). The differences were attributable mostly to decreases in neutrophils in DEXA-treated animals. In control animals, neutrophil yield fell between 8 and 32 h, whereas eosinophils and 32 h, whereas eosinophil and lymphocyte counts increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214948 TI - Long-term variability of bronchial responsiveness to histamine in a random population sample of adults. AB - Long-term variability of bronchial responsiveness has been studied in a random population sample of adults. During a follow-up period of 18 yr, 2,216 subjects contributed 5,012 observations to the analyses. Each subject could have as many as seven observations. Bronchial responsiveness was assessed with a histamine challenge test. The threshold value was defined as the concentration of histamine that caused a decrease in FEV1 of 10% of more (PC10). After a 3-yr interval, a change of the threshold value with two or more doubling concentrations occurred in 21% of the subjects. This proportion increased to 43% if the time between two measurements increased to 18 yr. Of all subjects with multiple observations, 41% were always nonresponders (PC10 > or = 32 mg/ml), 11% were always responders (PC10 < or = 16 mg/ml), and 48% changed responder status. Of the subjects with greater than three observations, 65% changed responder status. Regression analyses, stratified by symptom status, sex, and smoking habit, were used to estimate intraclass correlation coefficients (ICC) as a measure of variability of responsiveness. On average, ICC values were low (0.40), also indicating considerable variability. With adjustment for FEV1, age, area of residence, and eosinophil count, the ICC values decreased slightly. This indicated that with adjustment, the total variability decreased more than the within-subject variability. ICC values did not differ significantly between asymptomatic and symptomatic subjects. Analyses of responsiveness as a binary variable revealed similar results. PMID- 8214949 TI - Exercise-induced refractoriness in asthmatic subjects involves leukotriene and prostaglandin interdependent mechanisms. AB - Exercise-induced bronchoconstriction is caused, in part, by leukotriene (LT)D4 release in asthmatic airways. Asthmatics become refractory to exercise bronchoconstriction with repeated challenges, due to inhibitory prostaglandin release. The purpose of this study was to test the hypothesis that exercise refractoriness is caused by LTD4-induced inhibitory prostaglandin release. Fourteen stable asthmatic subjects with exercise-induced bronchoconstriction were studied. On the first 2 days, subjects underwent two challenges, 1 h apart, with either exercise or inhaled LTD4. Eight subjects then took part in three double blind, randomized, placebo-controlled, crossover studies with flurbiprofen, a prostaglandin synthetase inhibitor, to determine whether cross refractoriness occurs between exercise and LTD4, whether flurbiprofen attenuates this effect, and whether flurbiprofen attenuates LTD4 tachyphylaxis. There was a reduction in the intensity of bronchoconstriction to the second challenge both with exercise (refractoriness) and with LTD4 (tachyphylaxis). The degrees of refractoriness and tachyphylaxis were correlated (r = 0.72, p = 0.005). Flurbiprofen attenuated LTD4 tachyphylaxis. Cross refractoriness occurred between exercise and LTD4, and flurbiprofen treatment also attenuated this effect. One hour after LTD4 challenge, the mean fall in FEV1 after exercise was 12.3% (%SEM 2.3) on placebo and 17.1% (%SEM 3.8) on flurbiprofen (p = 0.027). Similarly, 1 h after exercise, the LTD4 PC20 increased to 0.73 (%SEM 1.4) microgram/ml on placebo and 0.30 (%SEM 1.8) microgram/ml on flurbiprofen (p = 0.026). These results suggest that LTD4 released in asthmatic airways as a result of exercise stimulates inhibitory prostaglandin release, resulting in exercise refractoriness. PMID- 8214950 TI - Expired breath hydrogen peroxide is a marker of acute airway inflammation in pediatric patients with asthma. AB - Airway inflammation is important in the development and progression of many pulmonary disorders, including asthma. We hypothesized that the hydrogen peroxide (H2O2) concentration in expired breath may be a marker of airway inflammation. Expired breath condensate was collected by cooling and the H2O2 concentration was measured fluorimetrically. Thirty-five samples were collected from 22 pediatric patients with asthma who were 7 to 18 yr of age and from 11 healthy, nonasthmatic controls. Asthmatic subjects were determined to be well or sick (acute disease of the upper or lower respiratory tract) by clinical examination. Pulmonary function tests were determined to be abnormal if there was a > 15% reduction in FEV1 or > 20% reduction in FEF25-75 compared with baseline values. Expired breath H2O2 was elevated in asthmatic subjects compared with controls (0.81 +/- 0.70 versus 0.25 +/- 0.27 mumol/L). The difference was primarily due to elevation of H2O2 in sick asthmatic subjects, whose expired breath H2O2 level of 1.5 +/- 0.5 (n = 10) was different from that of well asthmatics (0.54 +/- 0.56, n = 25). There was a high correlation between expired breath H2O2 and clinical status. Elevation of expired H2O2 occurred with either acute upper or lower respiratory tract disease. There was no statistically significant correlation between expired breath H2O2 level and pulmonary function test results. We conclude that elevation of H2O2 in the expired breath condensate is a simple, noninvasive method that can be used as a biochemical marker of airway inflammation. PMID- 8214951 TI - Ambient ozone causes upper airways inflammation in children. AB - Ozone constitutes a major air pollutant in Western Europe. During the summer national air quality standards are frequently exceeded, which justifies concern about the health effects of ozone at ambient concentrations. We studied upper airways inflammation after ozone exposure in 44 children by repeated nasal lavages from May to October 1991. During this time period five to eight lavages were performed for each child. On 14 days following high ozone exposure (daily maximum > or = 180 micrograms/m3) 148 nasal lavages were performed, and on 10 days following low ozone exposure (daily maximum < or = 140 micrograms/m3) 106 nasal lavages were performed. A significant increase of intra-individual mean polymorphonuclear leukocytes (PMN) counts from low ozone days (median, 20.27 x 10(3)) to high ozone days (median, 27.38 x 10(3); p < 0.01) was observed. Concomitant with a decrease of ozone concentrations in the fall mean PMN counts showed a downward trend. Linear regression analysis of log-PMN counts yielded a significant effect for ozone (p = 0.017). In a subsample humoral markers of inflammation were measured for each child's highest and lowest exposure. A significant increase was observed for eosinophilic cationic protein (median, 77.39 micrograms/L on low ozone days versus 138.6 micrograms/L on high ozone days; p < 0.05). Thus we conclude that ozone at ambient concentrations initiates a reversible inflammatory response of the upper airways in normal children. PMID- 8214952 TI - Effects of nitric acid gas alone or in combination with ozone on healthy volunteers. AB - Nitric acid (HNO3) is the most prevalent acid air pollutant in the western United States and has the potential to cause adverse respiratory effects through both acidification and oxidation reactions. To study this potential, we measured physiologic (specific airway resistance, SRaw, FEV1, and FVC) and bronchoalveolar lavage (total and differential cell counts, LDH, fibronectin, and total protein) end points in a group of 10 healthy, athletic subjects who were exposed to 500 micrograms/m3 of HNO3 gas or filtered air for 4 h during moderate exercise (ventilatory rate, 40 L/min) and underwent bronchoscopy 18 h later. Under an identical protocol, 10 healthy subjects were exposed to 500 micrograms/m3 of HNO3 gas plus 0.20 ppm ozone (O3) or 0.20 ppm O3 alone to determine if HNO3 might enhance the toxicity of O3. In addition to bronchoalveolar lavage (BAL), we employed the techniques of isolated left mainstem bronchial lavage and bronchial biopsy to determine if proximal airway injury was caused by pollutant exposure and whether there was any correlation with the degree of distal lung injury as assessed by BAL. We found no significant differences in pulmonary function tests or in the cellular or biochemical constituents in either the BAL or the left mainstem lavage fluids between the HNO3 and the air exposures. Similarly, there were no differences in these end points between the HNO3/O3 and the O3 exposures. Furthermore, there were no significant differences in the bronchial biopsy specimens between the HNO3 and air exposures or between the HNO3/O3 and O3 exposures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214953 TI - Investigation of a unique time-space cluster of sarcoidosis in firefighters. AB - A unique cluster of three cases of sarcoidosis developed recently among 10 white firefighters who trained together as apprentices in 1979. This led us to hypothesize that firefighters are at increased risk of this condition because of the combined effect of smoke exposure and infection with a communicable agent, such as Chlamydia pneumoniae, a recently proposed cause of sarcoidosis. We conducted a case-finding questionnaire survey of 1,282 active and retired male Providence firefighters and police officers and then evaluated both the index apprenticeship class and two control cohorts by chest radiography, seromarkers of T lymphocyte activation (neopterin and sIL-2R), and chlamydial serology. One additional case of sarcoidosis was identified among the 990 (77%) survey respondents. No new cases were detected in the subsequent laboratory investigation of 46 (87%) firefighters from the index 1979 apprenticeship class, 53 (75%) firefighter controls from the 1974 and 1980 classes, or 50 (30%) police officer controls from 1973-1981 classes. The cohorts did not differ with regard to either C. pneumoniae antibody titers or sIL-2R levels, but serum neopterin was elevated (> 9.0 nmol/L) in 20% (eight of 41) of the index cohort, 22% (11 of 51) of firefighter controls, and 4% (two of 48) of police officers. Logistic regression found firefighting to be the only significant predictor of neopterin elevation (odds ratio 5.8; 95% CI, 1.3 to 26.9). Our results suggest that firefighters may be at risk of T lymphocyte activation. Determining whether this reflects an enhanced risk of lymphocytic alveolitis and whether firefighters are more likely to develop sarcoidosis requires further study. PMID- 8214954 TI - The left-sided predominance of asbestos-related pleural disease. AB - In a series of 406 subjects with a diagnosis of asbestos-related pleural disease (ARPD), the left-right symmetry of radiographically diagnosed ARPD was assessed using the International Labour Organization (ILO) system for classifying radiographic abnormalities and three different statistical models for testing the degree of symmetry. The extent of chest disease was found to be greater on the left than on the right for a number of parameters of pleural disease, including the width and extent of localized pleural thickening, the extent of enface pleural thickening, and the extent of diaphragmatic and chest wall calcification. Current cigarette smoking significantly enhanced the observed asymmetry, with the most pronounced effect being in diaphragmatic calcification. Using a composite scale for each subject's pleural disease, the left side had 1.6 times more localized disease than did the right (p < 0.001). Asymmetry in one parameter was associated with asymmetry in another for a number of pairs. The most significant of these associations was between enface pleural thickening and chest wall calcification (Kendall's tau B = 0.42). The pathophysiologic mechanisms that explain these findings remain elusive and need further investigation. PMID- 8214955 TI - Epidemiology of beryllium sensitization and disease in nuclear workers. AB - We examined the epidemiology of chronic beryllium disease among a stratified, random sample (n = 895) of nuclear weapons workers using the blood beryllium lymphocyte transformation (BeLT) test and chest radiograph for case identification. Of 18 new cases of beryllium sensitization, 12 had beryllium disease, and three more developed pulmonary granulomas on lung biopsy over the succeeding 2 yr. Beryllium-sensitized cases did not differ from noncases in age, gender, race, ethnicity, smoking, most respiratory symptoms, spirometric or radiographic abnormalities, or job tenure. The six sensitized cases without initial disease differed from beryllium disease cases in having greater pack years of smoking. Sensitization occurred among workers with inadvertent or bystander exposure, such as a secretary and security guard. However, beryllium sensitization risk was higher for machinists (4.7%) and for persons reporting measured overexposure (7.4%, odds ratio 5.1); exposure beginning before 1970 (3.6%, odds ratio 2.7); consistent beryllium exposure (3.4%); and sawing (4.7%) or band sawing (6.0%) of beryllium metal. We conclude that both individual susceptibility to sensitization and exposure circumstances are important in developing disease. PMID- 8214956 TI - Pseudomonas aeruginosa bronchopulmonary infection in late human immunodeficiency virus disease. AB - Pseudomonas aeruginosa infection is unusual in individuals with human immunodeficiency virus infection, and it most often occurs in the setting of other risk factors, such as neutropenia or cytotoxic drug use. We noted an increasing number of pulmonary isolates of this organism in our clinic population and sought to describe the clinical correlates of this finding. Our study consisted of a retrospective review of the microbiology, radiology, and clinical records of 1,852 HIV-seropositive adults seen at a university-based outpatient AIDS clinic. We identified 16 individuals with Pseudomonas bronchopulmonary infection. All subjects had advanced HIV disease with prior AIDS diagnoses, and mean CD4 counts of 25/mm3 (0.025 x 10(9)/L). Pseudomonas was the sole pulmonary pathogen in 14 of 16 patients and was associated with new chest X-ray abnormalities in 14 cases. Four individuals had acute pseudomonal pneumonia with sepsis; this presentation was associated with hospitalization and other known risk factors for Pseudomonas infection. In contrast, 12 patients had more indolent, community-acquired infection, which had a low mortality rate and occurred in the absence of other risk factors. Survivors of the initial bout of Pseudomonas infection had an 86% relapse rate despite a median survival of only 4.5 months. This pattern of pseudomonal disease is reminiscent of cystic fibrosis and suggests a role for maintenance therapy. PMID- 8214958 TI - Efficacy and safety of inhaled corticosteroids in asthma. Report of a workshop held in Eze, France, October 1992. AB - Inhaled glucocorticosteroids have now become first-line therapy for the treatment of chronic asthma in many countries. They are the most effective asthma therapy currently available, and numerous studies have documented their long-term efficacy in asthma control in adults and in children. Inhaled steroids suppress inflammation in asthmatic airways, although their precise molecular mechanism of action is not yet certain. It is likely that steroids affect the transcription of several steroid-responsive genes, and, of particular importance, they may inhibit cytokine gene transcription and cytokine effects, thereby reducing the chronic inflammation in asthmatic airways. Inhaled steroids are now used at a much earlier stage in asthma therapy, and there is a strong argument for their early introduction in both adults and children to prevent asthma morbidity and mortality and possibly the structural changes resulting from uncontrolled chronic inflammation, which may lead to irreversible airflow obstruction in some patients. Of paramount importance is the question of safety as inhaled steroids are likely to be required for a long time. Local side effects caused by oropharyngeal deposition of the inhaled steroid may be reduced by the use of spacer devices and mouthwashing. Systemic side effects caused by gastrointestinal absorption of the fraction deposited in the oropharynx may also be reduced by these devices. There are differences in the systemic bioavailability of the different inhaled steroids currently in use, and inhaled steroids with the lowest bioavailability should be chosen when high doses of inhaled steroids are required for asthma control. Systemic side effects are usually observed only when daily doses of > 800 micrograms are inhaled, and whether effects on very sensitive biochemical indices are relevant to long-term deleterious effects is not yet certain. There is now overwhelming evidence that the doses of inhaled steroids required to control asthma in the majority of adults and children are safe and without systemic side effects. It is important to control asthma with the minimum dose of inhaled steroids possible, however. In the future it may be possible to develop inhaled steroids with even fewer systemic effects if the fraction absorbed from the respiratory tract can be rapidly metabolized in the bloodstream. PMID- 8214957 TI - Clinical evaluation of rapid serodiagnosis of pulmonary tuberculosis by ELISA with cord factor (trehalose-6,6'-dimycolate) as antigen purified from Mycobacterium tuberculosis. AB - Immunoglobulin G (IgG) antibodies against purified cord factor (trehalose-6,6' dimycolate) prepared from Mycobacterium tuberculosis H37Rv were determined by enzyme-linked immunosorbent assay (ELISA), and its diagnostic usefulness was evaluated. Serum specimens from 65 patients with active pulmonary tuberculosis, 58 patients with inactive pulmonary tuberculosis, 36 patients with diseases other than tuberculosis, and 66 healthy adults were examined. Patients with active pulmonary tuberculosis showed significantly higher titers of IgG antibodies against cord factor than did other groups (p < 0.001). The antibody titer greater than 0.29 in absorption difference (492 to 630 nm) of 160-times diluted serum was set as positive in ELISA. For patients with active and untreated pulmonary tuberculosis, the ELISA had a sensitivity of 81% and a specificity of 96%. From these results, it was concluded that the detection of IgG antibodies against cord factor is useful for serodiagnosis of active pulmonary tuberculosis. It was also indicated that the anticord factor antibody titers decline to the normal level as a result of antituberculosis chemotherapy. PMID- 8214959 TI - Results of Heineke-Mikulicz type choledochoplasty in benign biliary strictures. AB - During a 20-year period from 1970 to 1991, a total of 30,800 patients underwent biliary tract surgery at the Department of Surgery, University of Chile Clinical Hospital. Of these, seven female adults with a mean age of 39.7 years (range 29 to 54) were considered for analysis in this study. The results of the Heineke Mikulicz type choledochoplasty repair in patients with short localized strictures of the biliary tract were analyzed in these patients. In six cases, the repair was performed at a mean time of 20 months after cholecystectomy and accidental injury of the common bile duct; in one case it was carried out during cholecystectomy and repair of a Mirizzi type II cholecysto-hepatic fistula. This patient remained asymptomatic during a follow-up of 120 months. Of the six cases on whom choledochoplasty was performed as treatment of short strictures, five patients (83%) developed a new stricture at a mean time of 14 months after surgery; a hepatico-jejunostomy was performed in all. After this procedure, only one patient was re-operated again, and all remained asymptomatic long after surgery. We believe that this Heineke-Mikulicz type choledochoplasty, which has been recommended in short distal strictures, is not advisable as a definitive surgical repair for this kind of stricture. PMID- 8214960 TI - Nasogastric decompression following elective colorectal surgery: a prospective randomized study. AB - A prospective, randomized study was conducted to determine the need for nasogastric decompression following elective colorectal surgery for malignant and premalignant lesions. Seventy-seven consecutive patients were randomly assigned to one of two groups: Group 1--nasogastric decompression was maintained postoperatively until resumption of bowel function; Group 2--the nasogastric tube was removed in the recovery room. Forty patients were assigned to Group 1 (21 males, 19 females) and 37 to Group 2 (22 males and 15 females). Eleven patients in Group 1 (28%) developed nausea postoperatively, with six patients (15%) having an average of less than two emeses and five (12%) requiring nasogastric reintubation. Thirteen patients in Group 2 (35%) developed nausea, with 10 patients (27%) having an average of two emeses and three (8%) requiring nasogastric intubation (P = 0.80). Abdominal distention was observed in 13 patients (32%) in both Group 1 (32%) and Group 2 (35%). Two of the latter patients required nasogastric reintubation. Postoperative fever was noted in 23 patients (58%) in Group 1 and 14 (38%) in Group 2 (P = 0.13); atelectasis was diagnosed in 38 per cent of patients in Group 1 and 14 per cent in Group 2 (P = 0.03). These data support that nasogastric decompression is not necessary following elective colorectal surgery for malignant and premalignant lesions. PMID- 8214961 TI - Gastrointestinal bleeding caused by angiodysplasia: a difficult problem in patients with chronic renal failure receiving hemodialysis therapy. AB - Anemia in patients with renal failure is a common problem. Bleeding from small angiodysplastic lesions within the gastrointestinal tract appears to be a significant source of blood loss in some patients with renal failure receiving chronic hemodialysis. We describe a group of patients treated with estrogen therapy who had amelioration of their bleeding tendency. Correction of bleeding time may be one potential mechanism for this action. PMID- 8214962 TI - Results using the biofragmentable anastomotic ring for colon anastomosis. AB - The Biofragmentable Anastomotic Ring (BAR) (Valtrac, Davis & Geck, Inc.) is a newly approved device intended for colonic anastomosis. We have used the device in 47 patients to date. These patients were studied to determine the effectiveness, uses and limitations of this new device. The BAR is similar in concept to the older Murphy "Button" used circa World War I, but it's constructed of polyglycolic acid rather than metal. Anastomosis is effected by placing the two bowel lumens over the device, tying the purse-string sutures snugly, and "clicking" the device closed. The BAR fragments and is passed 2 to 3 weeks postoperatively. The patients ranged from 14 to 82 years of age. Thirty-nine patients were operated on for cancer, four for diverticulitis, and four for colostomy closure. One transverse colectomy (THC), 15 left hemicolectomies (LHC), 23 sigmoid colectomies (SC), two low anterior resections (LAR), four colostomy closures, and two right hemicolectomies were performed. There were no anastomotic leaks and no complications. We found that because of the need to have access distally to "click" the device closed, BAR anastomosis after LAR is rarely feasible. Because of the small lumenal size of the distal ileum, the BAR is seldom usable for ileocolonic anastomosis after right hemicolectomy (RHC). The newly approved 25-mm BAR may change this. We found that the time required to perform an anastomosis with the BAR is equivalent to stapled techniques. At our hospital, the cost of the device is equivalent to one intestinal stapler. Since multiple staplers are used in most colon anastomotic techniques, there is a modest cost advantage for the BAR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8214963 TI - Etiology and outcome of total parenteral nutrition-induced hepatic dysfunction. AB - Hepatic dysfunction is commonly encountered during total parenteral nutrition (TPN), but it is likely that factors other than TPN play an important role. This study divides TPN patients, before TPN administration, into two groups according to whether the pre-TPN liver function test was normal or abnormal. Among the 729 cases studied, liver function impairment was progressively downhill in patients with abnormal pre-TPN liver function, but liver function maintained normal in most patients with normal pre-TPN liver function test. The TPN formula did not differ between the two groups. Thus, TPN formula itself is probably not a crucial causal factor for hepatic dysfunction. Instead, the etiology of that dysfunction is more likely a result of multiple factors. From this study, it is suggested that digestive disease, nothing per os, and infections all play an important role (P < 0.001). The rates of morbidity, mortality, and organ failure are significantly increased in the group with abnormal pre-TPN liver function (P < 0.05). Aggressive treatment of underlying disease and early restoration of enteral feeding are suggested to reduce TPN-induced hepatic dysfunction. PMID- 8214964 TI - Postoperative bowel obstruction following laparoscopic surgery. AB - The rapid expansion of laparoscopic surgery has not been achieved without attendant complications, some of them unique. Visceral herniation into abdominal trocar entry sites is occasionally mentioned but seldom reported. We present three cases of postoperative bowel obstruction resulting from visceral herniation into trocar entry sites in different surgical settings, suggesting that this complication may be more common than is appreciated. Awareness of this clinical problem confirms the need for meticulous closure of larger abdominal trocar sites and should be considered when dealing with abdominal disorders following laparoscopic surgery. PMID- 8214965 TI - Elective one-stage abdominal operations after percutaneous catheter drainage of pyogenic liver abscess. AB - During the past 10 years, 15 patients have had percutaneous catheter drainage (PCD) of pyogenic liver abscesses (PLA) at a major teaching hospital. Five PLA were related to biliary tract disease, two were secondary to colonic diverticulitis, two developed after abdominal surgery, and the remaining were associated with hepatic trauma, gastric ulcer, Crohn's ileitis, and colon cancer. Two abscesses were cryptogenic. Mean diameter of PLA was 8 cm and ranged from 2 14 cm. Three patients had multiple PLA. All patients were initially treated by PCD without major complications. However, one patient required a second PCD after developing a recurrent abscess. Fever and leukocytosis defervesced at a mean 3.6 days and 7 days, respectively, after PCD. Seven of the 15 patients subsequently had one-stage elective abdominal operations for treatment of diseases underlying PLA including two cholecystectomies, two colon resections, one gastrectomy, one ileostomy closure, and one laparotomy for unresectable gall bladder cancer. There were no postoperative complications. These results demonstrate that PLA are best treated by using PCD as primary treatment with surgical drainage reserved for patients who do not respond clinically to PCD. The need for operative treatment in diseases underlying PLA should not deter use of PCD as primary treatment. PMID- 8214966 TI - Hepatic duct transection during laparoscopic cholecystectomy. AB - A rare anatomical variation was encountered during a laparoscopic cholecystectomy. The right hepatic duct emptied into the infundibulum of the gallbladder. This confluence then joined the left hepatic duct to form the common bile duct. The right hepatic duct was transected between the gallbladder and the common bile duct as a normal cystic duct would have been isolated and divided laparoscopicaly. This anatomic variant was recognized after further mobilization of the gallbladder from the liver bed. A laparotomy was performed to create a right hepatic duct enteric anastomosis. The case illustrates one possible pitfall that may be encountered during laparoscopic cholecystectomy. PMID- 8214967 TI - Clinical presentation of chronic anal fissures. AB - Chronic anal fissures have a varied and often confusing clinical presentation. To clarify this picture, we retrospectively studied 172 patients to determine associations between patient characteristics and manifestations of these lesions. We found that anterior fissures and sentinel piles were significantly more common in women; pruritus and rectal drainage occurred significantly more often in men; and patients with a longer duration of symptoms and those with pruritus and drainage were more likely to have a fistula. Younger patients were more likely to report rectal bleeding. Patients with chronic anal pruritus or an anal abscess should be carefully evaluated for an anal fistula, since anorectal problems may recur if a fistula remains untreated. PMID- 8214968 TI - Perforated gastric ulcers: resection compared with simple closure. AB - One hundred thirty-four patients with perforated gastric ulcers who underwent emergency surgery at a tertiary referral center during a 20-year period were reviewed. Short-term outcome of 94 patients whose perforation was simply closed was compared with 40 who had a gastrectomy. Morbidity (simple closure 51%; resection 45%) and mortality (simple closure 10.6%; resection 7.5%) were similar, but four deaths after simple closure were procedure-related. In patients older than 65 years, morbidity (67%) and mortality (24%) increased significantly. The higher mortality in the elderly was particularly apparent after simple closure (29% vs 11%), but this may reflect selection bias. Simple closure is safe and effective in the majority of patients with perforated gastric ulcers. However, our data indicate that gastrectomy can be performed safely even in high risk cases and should be considered where there is a well documented history of chronicity or when the nature of the ulcer, or associated ulcer hemorrhage, preclude safe simple closure. PMID- 8214969 TI - The Stamm gastrostomy: a sound procedure. AB - A review of 100 personal cases of open gastrostomy using a modified Stamm technique showed that the majority (82.7%) could be performed using local anesthesia with intravenous sedation. Only one patient suffered a wound infection, and there were no other technical complications. The use of a separate stab wound for the introduction of the tube and the routine use of antibiotic irrigation might have contributed to the reduction of wound complications. The overall mortality was 18 per cent, and all of the deaths were due to the patients underlying diseases. The Stamm procedure, which can be performed under local anesthesia without undue discomfort in the majority of patients, has a very low morbidity and no intrinsic mortality. It has a proper place in the armamentarium of nutritional support for these terminally ill patients. PMID- 8214970 TI - The management of massive lower gastrointestinal bleeding. AB - To evaluate what has been the most effective surgical treatment for massive lower gastrointestinal bleeding, we reviewed the records of 31 patients who underwent colon resection for hemodynamic instability and/or the need for continued transfusions. These 31 patients underwent either segmental colectomy (21 patients) or subtotal colectomy (10 patients). Resections were performed for diverticular disease (19 patients), angiodysplasia (eight patients), acute ulceration (three patients), and polyps (one patient). The re-bleeding rate (mean follow-up 1 year) for subtotal colectomy was 0 per cent, segmental resection with positive angiography was 14 per cent, and segmental resection with negative angiography was 42 per cent. The complication rate including myocardial infarction, ARDS, pneumonia, and renal failure was highest (83 per cent) in those patients receiving segmental resection with a negative angiogram. The mortality rate was also highest for segmental resection patients with negative angiography (57 per cent). The results of this review suggest that segmental resection should be performed when the bleeding site is identified angiographically. Subtotal colectomy should be reserved for massive bleeding with negative angiography. PMID- 8214971 TI - Cytomegaloviral acalculous cholecystitis in acquired immunodeficiency syndrome patients. AB - Abdominal pain and fever in patients with the acquired immunodeficiency syndrome (AIDS) may indicate cytomegaloviral (CMV) acalculous cholecystitis. We reviewed clinical, laboratory, and outcome data from 12 patients with CMV cholecystitis. Ten of 12 patients were homosexual males. Six patients had markedly low CD4: CD8 lymphocyte count ratios. Total leukocyte counts were normal or decreased, serum liver function tests normal or cholestatic, and only one patient had hyperbilirubinemia. Sonographic transmural gallbladder edema is typically more severe than expected for the presenting illness. Five of six patients investigated with HIDA scintigraphy had a nonvisualizing gallbladder. Open cholecystectomy had a 9.1 per cent operative morbidity and a 0 per cent mortality. Cholecystectomy is a safe and curative intervention, regardless of the immunocompromised condition of the host. Intraoperative cholangiography will identify papillary stenosis or sclerotic bile ducts as a potential cause of recurrent symptoms following surgery. A search for other sites of tissue invasion by CMV should follow cholecystectomy. PMID- 8214972 TI - Duodenectomy and reimplantation of the ampulla of Vater for megaduodenum. AB - After several unsuccessful surgical procedures, a case of megaduodenum in a 29 year-old woman was treated successful with duodenal resection and reimplantation of the ampulla with a Roux en Y limb of jejunum. Alternate approaches to this complicated condition are discussed. PMID- 8214973 TI - Cardiorespiratory effects of laparotomy in patients with spinal cord injury. AB - Patients with spinal cord injuries who require laparotomy are often difficult to diagnose and have an acute illness superimposed on a background of respiratory and cardiovascular abnormalities. Although pulmonary capacity is markedly reduced by paralysis, these patients tolerate elective laparotomy well. Emergency surgery for abdominal infection led to cardiac instability in two patients and prolonged respirator support in a third. This series of 12 patients supports elective colostomy for colon and perineal problems in these patients, even those with poor ventilatory volumes. Emergency surgery was marked by dramatic cardiovascular problems, which were corrected with pulmonary artery pressure monitoring of fluid resuscitation. PMID- 8214974 TI - Vascular injuries during pancreatobiliary surgery. AB - Fourteen cases of vascular injury during pancreatobiliary surgery have been treated at our institution. The patients' mean age was 49 years, and nine were males. Six operations were performed for chronic pancreatitis, six for cancer, and two for an inflammatory process. Operations included 11 pancreatic resections and one laparoscopic cholecystectomy, one sphincteroplasty, and one pseudocyst drainage. Vessels injured included the portal vein (7), superior mesenteric vein (6), superior mesenteric artery (3), hepatic arteries (4), splenic vein (3). Six patients experienced more than one vascular injury. In all but one case, the injury was recognized and repaired during the initial operation. Primary repair was possible in seven cases. Six cases utilized autogenous tissue for repair. The one unrecognized injury was a right hepatic artery ligation, and a delayed repair was not possible. Follow-up demonstrated two occlusions, one following a portal vein repair without clinical sequela and a superior mesenteric artery repair which resulted in a small bowel stricture. The one unrecognized hepatic artery injury resulted in necrosis of the proximal common hepatic duct. Vascular injury following pancreatobiliary injury tends to occur in the presence of pancreatitis or cancer with its associated dense adhesions and inflammatory process. The variable anatomy of this area contributes to vascular injuries. Immediate recognition of the injury and repair appears to yield excellent results. PMID- 8214975 TI - The advantages of early operation with splenorrhaphy versus nonoperative management for the blunt splenic trauma patient. AB - The importance of splenic preservation in reducing the risk of overwhelming post splenectomy sepsis as well as the heightened awareness of transfusion-related infections have led to changing concepts in the management of blunt splenic trauma. A 10-year retrospective review (1980-1989) of blunt splenic trauma at a Level I trauma center is presented. One hundred eighty five blunt splenic injuries were treated, with a mortality rate of 7 per cent. Splenorrhaphy was performed in 7 per cent of patients in the first 5-year period (48% underwent splenectomy, and 45% were managed nonoperatively). The rate of splenorrhaphy increased to 22 per cent during the second 5-year period, with a subsequent decrease in both splenectomy (39%) and nonoperative management (39%). During the last year of review, 65 per cent of bluntly injured spleens were able to be salvaged (35% managed by splenorrhaphy and 30% by observation). Blood usage averaged 1.1 units/patient in the nonoperative group, 3.3 units/patient in the splenorrhaphy group, and 7.9 units/patient in those undergoing splenectomy. Nonoperative management of blunt splenic trauma can clearly be successful. However, patients chosen for this method should be completely hemodynamically stable to avoid requiring blood transfusions. A combination of early operation and splenorrhaphy with the use of autotransfusion devices, remains a better alternative in the less stable patient with multiple injuries. This method provides for a high rate of splenic salvage while decreasing the need for homologous blood transfusions. PMID- 8214976 TI - A new bedside test of cognition for patients with HIV infection. AB - OBJECTIVE: To compare the Mental Alternation Test, a new 60-second bedside test of cognition, with the Mini-Mental State Exam (MMSE) and the Trailmaking Test, parts A and B, in patients with human immunodeficiency virus (HIV) infection. DESIGN: Cohort study. PARTICIPANTS: Sixty-two inpatients with HIV infection. SETTING: The AIDS service of a referral hospital. MEASUREMENTS: Scores on the MMSE; the Trailmaking Test, parts A and B; and the Mental Alternation Test were compared using correlation calculations and analyses of variance. Receiver operating curves were constructed to identify the best cutoff score on the Mental Alternation Test for detecting impaired performance on the MMSE and the Trailmaking Test. MAIN RESULTS: The Mental Alternation Test score correlated significantly with MMSE (r = 0.68, P < 0.01) and Trailmaking Test, part B, scores (r = -0.54, P < 0.01). The receiver operating curves showed that a Mental Alternation Test cutoff score of 15 yielded the best results for the detection of abnormal performance on the MMSE (sensitivity, 95% [95% CI, 90% to 100%]; specificity, 79% [CI, 69% to 89%]) and the Trailmaking Test, part B (sensitivity, 78% [CI, 68% to 88%]; specificity 93% [CI, 90% to 100%]). Patients making fewer than 15 alternations in 30 seconds were significantly more likely to have abnormal MMSE (P < 0.0001) and Trailmaking Test, part B, scores (P < 0.0001). The Mental Alternation Test had good reproducibility; analyses of reliability included test-retest correlation (r = 0.80) and inter-rater reliability (r = 0.85, kappa = 0.84). Time of administration was approximately 60 seconds. CONCLUSIONS: The Mental Alternation Test of cognition has good sensitivity and specificity and is easily administered. It is a valuable test to identify patients who may need further cognitive evaluation. PMID- 8214977 TI - Autoantibody reactive with RNA polymerase III in systemic sclerosis. AB - OBJECTIVE: To determine the clinical significance of anti-RNA polymerase III antibody in systemic sclerosis (SSc). DESIGN: A point prevalence study of autoantibody to RNA polymerase III and longitudinal examination of its clinical significance in patients with SSc and in controls. SETTING: University medical center rheumatology practice. PATIENTS: Two hundred fifty-two consecutive new patients with SSc and 170 controls (150 patients with other connective tissue diseases and 20 normal volunteers). MEASUREMENTS: The presence of anti-RNA polymerase III antibody was determined by immunoprecipitation, immunoblotting, and immunodepletion studies. MAIN RESULTS: Serum specimens from 57 of the 252 patients with SSc (23%; 95% CI, 18% to 28%) reacted with RNA polymerase III, compared with none of the specimens from 170 controls (0%; 95% CI, 0% to 2%). In 40 of these 57 specimens, immunoprecipitation studies also showed the presence of RNA polymerase I or II, or both. Anti-RNA polymerase III antibody was detected in sera from 50 of the 111 patients (45%) who had SSc with diffuse cutaneous involvement (dcSSc), 7 of 114 patients (6%) who had SSc with limited cutaneous involvement, and none of 27 patients with an SSc overlap syndrome (P < 0.001). Among patients with dcSSc, anti-RNA polymerase III antibody was more common than antitopoisomerase I antibody (45% compared with 27%; P = 0.008). Patients with anti-RNA polymerase III antibody had a statistically significant higher mean maximum skin thickness score but statistically significant lower frequencies of telangiectasias, inflammatory myopathy, restrictive lung disease, and serious cardiac abnormalities than did patients with antitopoisomerase I antibody. CONCLUSION: Anti-RNA polymerase III antibody is a new marker autoantibody for many patients who have SSc with diffuse or extensive cutaneous involvement. PMID- 8214978 TI - Successful treatment of refractory sprue with cyclosporine. PMID- 8214979 TI - The medical complications of drug addiction and the medical assessment of the intravenous drug user: 25 years later. AB - PURPOSE: To review changes in the medical complications of drug abuse that have occurred since the authors reviewed them 25 years ago. DATA SOURCE: Manual search of the internal medicine and subspecialty literature of the past three decades that was selected by the authors. STUDY SELECTION: Selected studies were of three types--baseline studies for the period ending in 1968, studies after 1968 that emphasized changes from baseline, and studies after 1968 that emphasized change (or the absence of change) and the manner in which clinicians conceptualized problems. DATA EXTRACTION: We extracted data that showed changes in the diseases, the appearance of new diseases, or the disappearance of formerly common diseases. RESULTS OF DATA SYNTHESIS: The diseases complicating drug abuse are now more widely disseminated than they were in the last 25 years. Some former "diseases of addiction" such as tetanus and malaria are now rare. Diseases (such as human immunodeficiency virus infection) not known to exist or rare 25 years ago now occur frequently. The drugs of abuse have also changed; for example, cocaine is now much more common. CONCLUSIONS: Treating the acute medical problems (mostly infectious diseases) in poor, undereducated, and often noncompliant intravenous drug users is far more complex than previously described. Although some features have remained constant, the emergence of human immunodeficiency virus infection and changes in patterns of drug use have radically altered patient management. PMID- 8214980 TI - Contributions of obesity and weight loss to gallstone disease. AB - OBJECTIVE: To examine the relation of obesity and weight loss to the formation of gallstones according to pertinent clinical and research issues. DATA SOURCES AND EXTRACTION: Original reports obtained through a MEDLINE search from 1966 to 1992 on gallstones plus obesity or reducing diets, supplemented by a manual search of bibliographies, a Current Contents title search from 1991 to 1992 on gallstones and gallbladder, and expert opinion. Only studies of humans were cited. DATA SYNTHESIS: For women, but less so for men, obesity is a strong risk factor for gallstones, and this risk is increased during weight loss. Between 10% and 25% of obese men and women may develop gallstones within a few months of beginning a very low calorie diet, and perhaps one third of these will develop symptoms of gallstones. Persons with the highest body mass index before weight loss and those who lose weight most rapidly appear to be at the greatest risk for gallstones. Treatment with ursodeoxycholic acid (ursodiol) during weight loss dieting is the only proven prevention for the formation of gallstones. Issues to be resolved include how different diets affect the risk for developing gallstones, the identification of other risk factors for gallstone formation during weight loss, the effect of weight loss among people with preexisting gallstones, and the optimum means of preventing gallstones during weight loss. CONCLUSIONS: During weight loss, particularly among the obese, an increased risk exists for symptomatic gallstone formation. This acute risk offers the opportunity to investigate the cause of gallstones and possibly to prevent them. PMID- 8214981 TI - The introduction of computer-based patient records in The Netherlands. AB - Computer-based patient records, although an area of active research, are not in widespread use. In June 1992, 38% of Dutch general practitioners had introduced computer-based patient records. Of these, 70% had replaced the paper patient record with a computer-based record to retrieve and record clinical data during consultations. Possible reasons for the use of computer-based patient records include the nature of Dutch general practice and the early and active role of professional organizations in recognizing the potential of computer-stored patient records. Professional organizations issued guidelines for information systems in general practice, evaluated available systems, and provided postgraduate training that prepares physicians to use the systems. In addition, professional organizations successfully urged the government to reimburse general practitioners part of the expenses related to the introduction of computer-based patient records. Our experience indicates that physicians are willing and able to integrate information technology in their practices and that professional organizations can play an active role in the introduction of information technology. PMID- 8214982 TI - Tobacco, tulips, and terminal care. PMID- 8214983 TI - Illicit drug use revisited: what a long, strange trip it's been. PMID- 8214984 TI - The computer-based clinical record--where do we stand? PMID- 8214985 TI - Didanosine-induced disorders of glucose tolerance. PMID- 8214986 TI - Quantifying lymphocytes in bronchoalveolar lavage fluid. PMID- 8214987 TI - Effect of inhaled steroids on the course of asthma. PMID- 8214988 TI - Isolated right ventricular infarction. PMID- 8214989 TI - Reversible marked splenomegaly in pernicious anemia. PMID- 8214990 TI - Silicone breast implants and atypical autoimmune disease. PMID- 8214991 TI - Cost-effectiveness of prostate cancer screening and treatment. PMID- 8214992 TI - Cost-effectiveness of prostate cancer screening and treatment. PMID- 8214993 TI - Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS). AB - OBJECTIVE: To assess the effects of lipid-lowering therapy with lovastatin on coronary angiographic findings in patients with coronary artery disease and to compare the findings with those of two lipid-lowering angiographic trials using similar end points. DESIGN: Randomized, double-blind, placebo-controlled, multicenter coronary angiographic trial. SETTING: Community- and university-based cardiac catheterization laboratories. PARTICIPANTS: A total of 270 patients, 37 to 67 years old, with total cholesterol ranging from 4.92 to 7.64 mmol/L (190 to 295 mg/dL) and angiographically defined coronary artery disease. INTERVENTION: A cholesterol-lowering diet and either lovastatin, 80 mg/day, or placebo. OUTCOME: Per-patient change in percent diameter stenosis as determined by quantitative coronary angiography (primary end point). Global change score, based on the consensus of blinded expert readers regarding angiographic change (secondary endpoint). RESULTS: Lovastatin lowered total cholesterol level by 32%, low density lipoprotein cholesterol by 38%, and the apolipoprotein B by 26% and raised the high-density lipoprotein cholesterol by 8.5% (P < 0.001). Average percent diameter stenosis increased 2.2% in placebo recipients and 1.6% in lovastatin recipients (P > 0.20). For lesions 50% or greater, average percent diameter stenosis increased 0.9% in placebo recipients and decreased 4.1% in lovastatin recipients (P = 0.005). The mean global change score was +0.9 (indicating progression) in the placebo group and +0.4 in the lovastatin group (P = 0.002); 13 placebo recipients and 28 lovastatin recipients had global change scores indicating regression (P < 0.02). CONCLUSION: Treatment with lovastatin plus diet slows the rate of progression and increases the frequency of regression in coronary artery lesions (by global change score), especially in more severe lesions (by quantitative angiography). This is the third lipid-lowering trial to show a benefit using the global change score, an end point predictive of clinical coronary events. Differences between two of these trials, using quantitative coronary angiographic end points, may have theoretical bearing on the mechanisms by which lipid-lowering therapy operates at the level of the arterial wall. PMID- 8214994 TI - An algorithmic approach to chronic cough. AB - OBJECTIVES: To evaluate a stepwise approach to chronic cough that emphasized initial treatment of all patients with an antihistamine-decongestant for postnasal drip and to determine the value of routine bronchoprovocation challenge in the evaluation of chronic cough. DESIGN: Prospective trial using an algorithm for chronic cough in immunocompetent nonsmoking out-patients. SETTING: University based pulmonary practice. PATIENTS: Forty-five patients met the inclusion criteria. The mean duration of cough was 140 weeks (range, 3 to 2080 weeks), and the mean severity of cough as assessed by patients on a four-point scale was "severe." RESULTS: Marked improvement and resolution (mean, 3.1 and 7.1 weeks, respectively), with resolution in 96% of patients. Antihistamine-decongestant therapy was beneficial in 39 of 45 patients and was the only therapy needed for 16 patients. Bronchoprovocation challenge had a negative predictive value of 100% and a positive predictive value of 74% for cough caused by asthma. No significant relationship was found between the time to cough resolution and duration or severity of cough. Eighteen percent of patients experienced a recurrence of cough at a follow-up interval of 3 months. CONCLUSIONS: A sequential approach to chronic cough that emphasizes initial treatment with an antihistamine decongestant is effective. Bronchoprovocation challenge is useful in evaluating patients with chronic cough but can be delayed until the initial response to antihistamine-decongestant therapy has been assessed. The 18% incidence of recurrence highlights the fact that cough often is the manifestation of a chronic or recurring process that requires chronic or episodic therapy. PMID- 8214995 TI - Cytomegalovirus immune globulin prophylaxis in liver transplantation. A randomized, double-blind, placebo-controlled trial. AB - OBJECTIVE: To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants. DESIGN: Randomized, multicenter, placebo-controlled, double-blind trial. SETTING: Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). PATIENTS: One hundred forty-one liver transplant recipients completed the study. INTERVENTION: CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16. MEASUREMENTS: Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness. RESULTS: Using a Cox proportional hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group). CONCLUSION: CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies. PMID- 8214996 TI - Smoking cessation in relation to total mortality rates in women. A prospective cohort study. AB - OBJECTIVE: To examine the temporal relationship between stopping smoking and total mortality rates among middle-aged women. DESIGN: Prospective cohort study with 12 years of follow-up. SETTING: Registered nurses residing in the United States. PARTICIPANTS: 117,001 female registered nurses, ages 30 to 55 years, who were free of manifest coronary heart disease, stroke, and cancer (except nonmelanoma skin cancer) in 1976. MAIN OUTCOME MEASURES: Total mortality, further categorized into deaths from cardiovascular diseases, cancers, and violent deaths. RESULTS: A total of 2847 deaths (933 among "never smokers," 799 among former smokers, and 1115 among current smokers) occurred during 1.37 million person-years of follow-up. The multivariate relative risks for total mortality compared with never smokers were 1.87 (95% CI, 1.65 to 2.13) for current smokers and 1.29 (CI, 1.14 to 1.46) for former smokers. Participants who started smoking before the age of 15 years had the highest risks for total mortality (multivariate relative risk, 3.15; CI, 2.16 to 4.59), cardiovascular disease mortality (relative risk, 9.94; CI, 5.15 to 19.19), and deaths from external causes of injury (relative risk, 5.39; CI, 1.84 to 15.78). Compared with continuing smokers, former smokers had a 24% reduction in risk for cardiovascular disease mortality within 2 years of quitting. The excess risks for total mortality and both cardiovascular disease and total cancer mortality among former smokers approached the level of that for never smokers after 10 to 14 years of abstinence. The health benefits of cessation were clearly present regardless of the age at starting and daily number of cigarettes smoked. CONCLUSIONS: The risk of cigarette smoking on total mortality among former smokers decreases nearly to that of never smokers 10 to 14 years after cessation. PMID- 8214997 TI - Treatment of rheumatoid arthritis with gammalinolenic acid. AB - OBJECTIVE: To assess the clinical efficacy and side effects of gammalinolenic acid, a plant-seed-derived essential fatty acid that suppresses inflammation and joint tissue injury in animal models. DESIGN: A randomized, double-blind, placebo controlled, 24-week trial. SETTING: Rheumatology clinic of a university hospital. PATIENTS: Thirty-seven patients with rheumatoid arthritis and active synovitis. INTERVENTION: Treatment with 1.4 g/d gammalinolenic acid in borage seed oil or cotton seed oil (placebo). MEASUREMENTS: Physicians' and patients' global assessment of disease activity; joint tenderness, joint swelling, morning stiffness, grip strength, and ability to do daily activities. RESULTS: Treatment with gammalinolenic acid resulted in clinically important reduction in the signs and symptoms of disease activity in patients with rheumatoid arthritis (P < 0.05). In contrast, patients given a placebo showed no change or showed worsening of disease. Gammalinolenic acid reduced the number of tender joints by 36%, the tender joint score by 45%, swollen joint count by 28%, and the swollen joint score by 41%, whereas the placebo group did not show significant improvement in any measure. Overall clinical responses (significant change in four measures) were also better in the treatment group (P < 0.05). No patients withdrew from gammalinolenic acid treatment because of adverse reactions. CONCLUSION: Gammalinolenic acid in doses used in this study is a well-tolerated and effective treatment for active rheumatoid arthritis. Gammalinolenic acid is available worldwide as a component of evening primrose and borage seed oils. It is usually taken in far lower doses than used in this trial. It is not approved in the United States for the treatment of any condition and should not be viewed as therapy for any disease. Further controlled studies of its use in rheumatoid arthritis are warranted. PMID- 8214998 TI - The weight-based heparin dosing nomogram compared with a "standard care" nomogram. A randomized controlled trial. AB - OBJECTIVE: To determine whether an intravenous heparin dosing nomogram based on body weight achieves therapeutic anticoagulation more rapidly than a "standard care" nomogram. DESIGN: Randomized controlled trial. SETTING: Two community teaching hospitals in Phoenix, Arizona, and Rochester, New York. PARTICIPANTS: One hundred fifteen patients requiring intravenous heparin treatment for venous or arterial thromboembolism or for unstable angina. INTERVENTION: Patients were randomized to the weight-based nomogram (starting dose, 80 units/kg body weight bolus, 18 units/kg per hour infusion) or the standard care nomogram (starting dose, 5000-unit bolus, 1000 units per hour infusion). Activated partial thromboplastin time (APTT) values were monitored every 6 hours, and heparin dose adjustments were determined by the nomograms. MEASUREMENTS: Activated partial thromboplastin times were measured using a widely generalizable laboratory method. The primary outcomes were the time to exceed the therapeutic threshold (APTT > 1.5 times the control) and the time to achieve therapeutic range (APTT, 1.5 to 2.3 times the control). Bleeding complications and recurrent thromboembolism were also compared. RESULTS: Kaplan-Meier curves for the primary outcomes favored the weight-based nomogram (P < 0.001 for both). In the weight based heparin group, 60 of 62 patients (97%) exceeded the therapeutic threshold within 24 hours, compared with 37 of 48 (77%) in the standard care group (P < 0.002). Only one major bleeding complication occurred (in a standard care patient). Recurrent thromboembolism was more frequent in the standard care group; relative risk, 5.0 (95% CI, 1.1 to 21.9). CONCLUSIONS: The weight-based heparin nomogram is widely generalizable and has proved to be effective, safe, and superior to one based on standard practice. PMID- 8214999 TI - Cigarette smoking inhibits acid-stimulated duodenal mucosal bicarbonate secretion. AB - OBJECTIVE: To determine the effect of cigarette smoking on proximal duodenal mucosal bicarbonate secretion, an important defense mechanism against acid and peptic damage. DESIGN: Prospective study. SETTING: Clinical research laboratory in a university hospital. PATIENTS: Thirteen healthy adults (7 smokers and 6 nonsmokers) who had no history of peptic ulcer disease. INTERVENTIONS: Participants smoked (1 cigarette/15 min during a period of 1 hour, smokers only) or sham smoked (puffing on an unlit cigarette) during duodenal perfusion with either saline, hydrochloric acid, or prostaglandin E2 (PGE2). MEASUREMENTS: Collection of proximal duodenal secretions using a modified duodenal tube with occluding balloons and quantitation of duodenal mucosal bicarbonate secretion. RESULTS: During sham smoking both smokers and nonsmokers had comparable basal as well as H(+)-stimulated and PGE2-stimulated duodenal mucosal bicarbonate secretion. Compared with sham smoking, smoking did not significantly alter basal bicarbonate secretion (201 mumol/cm per hour [95% CI, 152 to 250 mumol/cm per hour] compared with 178 mumol/cm per hour [CI, 134 to 222 mumol/cm per hour], respectively). However, compared with sham smoking, smoking markedly reduced (P < 0.01) the increase in duodenal bicarbonate secretion in response to luminal acidification by approximately 80% (from 242 mumol/cm per hour [CI, 41 to 443 mumol/cm per hour] to 53 mumol/cm per hour [CI, -107 to 197 mumol/cm per hour]); a decrease was observed in each participant. In contrast, smoking had no significant effect on the response to luminal PGE2. CONCLUSIONS: Cigarette smoking markedly inhibited acid-stimulated human duodenal mucosal bicarbonate secretion. This adverse effect of smoking may, at least in part, explain the role of cigarette smoking in the pathogenesis and natural history of duodenal ulcer disease. PMID- 8215000 TI - Positive end-expiratory pressure increases the right-to-left shunt in mechanically ventilated patients with patent foramen ovale. AB - OBJECTIVE: To determine the effect of the presence of a patent foramen ovale on the right-to-left shunt in patients with respiratory failure who receive positive end-expiratory pressure (PEEP). DESIGN: Convenience sample with randomized application of PEEP. SETTING: General intensive care unit of a university teaching hospital. PATIENTS: A total of 46 mechanically ventilated patients with respiratory failure requiring an inspired oxygen concentration of at least 50% and a PEEP of at least 5 cm of H2O. INTERVENTION: Randomized application of PEEP (0 and 10 cm of H2O). MEASUREMENTS: A patent foramen ovale was detected by saline contrast transesophageal echocardiography. The alveolar-to-arterial oxygen difference and the right-to-left shunt were calculated from arterial and venous blood gas sampling. RESULTS: In patients without a patent foramen ovale (n = 39), the alveolar-to-arterial oxygen difference and the shunt fraction decreased (-50 mm Hg [95% CI, -21 to -67] and -0.05 [CI, -0.03 to -0.07], respectively) after adding PEEP (10 cm of H2O). In patients with a patent foramen ovale (n = 7), minimal changes were noted in the alveolar-to-arterial oxygen difference (4 mm Hg, P > 0.2), but the shunt fraction increased (0.05, CI, 0 to 0.09). Adding PEEP (10 cm of H2O) increased the shunt fraction in 6 of 7 (86%) patients with a patent foramen ovale, whereas the shunt increased in only 7 of 39 (18%) patients without a patent foramen ovale (P < 0.007). CONCLUSIONS: A patent foramen ovale was found in 7 of 46 patients (15%; CI, 6% to 29%) with acute respiratory failure. This condition is a common cause of lack of improvement in oxygenation with the addition of PEEP in the mechanically ventilated patient. In patients with a patent foramen ovale, the right-to-left shunt is usually increased by using PEEP. PMID- 8215001 TI - The role of Microsporidia in the pathogenesis of HIV-related chronic diarrhea. AB - OBJECTIVE: To determine whether infection with Microsporidia leads to diarrhea in patients with human immunodeficiency virus (HIV) infection. DESIGN: Case-control study. SETTING: Primary care outpatient HIV clinic at a Veterans Affairs medical center. PATIENTS: One hundred six HIV-infected men, 55 with and 51 without chronic diarrhea. MEASUREMENTS: Each patient underwent upper endoscopy and flexible sigmoidoscopy to obtain duodenal, rectal, and sigmoid colonic biopsy specimens. At the time of endoscopy, a fresh stool was obtained for culture, ova and parasite assessment, and Cryptosporidium examination. Biopsy tissue was examined using electron microscopy to detect Microsporidia. RESULTS: The microsporidian parasite Enterocytozoon bieneusi was detected in the duodenal biopsy specimens of 31 of 106 men (29%); 24 of 106 men (23%) had other enteric pathogens. No significant difference was observed in the occurrence of microsporidiosis in patients with (18 of 55 [33%]) and without (13 of 51 [25%]) chronic diarrhea (odds ratio, 1.42; 95% CI, 0.61 to 3.31). A similar nonsignificant difference was observed after controlling for CD4 count and other enteric pathogens (odds ratio, 1.66; 95% CI, 0.68 to 4.06). Among patients with microsporidiosis, no difference was observed in the intensity of infection (defined by the presence of few, moderate, or abundant organisms) among cases and controls (P > 0.2). CONCLUSIONS: This is the first report to document the presence of E. bieneusi in HIV-positive patients without gastrointestinal symptoms. No significant difference was observed in the occurrence of E. bieneusi infection in HIV-infected patients with or without chronic diarrhea. Thus, the association between microsporidiosis and diarrhea, if one exists, may not be as strong as is currently believed. PMID- 8215002 TI - Sudden death of a carrier of X-linked Emery-Dreifuss muscular dystrophy. AB - OBJECTIVE: To report a sudden death in a female carrier of Emery-Dreifuss muscular dystrophy and to describe the cardiac abnormalities associated with this disease. STUDY DESIGN: Case series. SETTING: University hospital. PATIENTS: A 45 year-old carrier who died suddenly and two affected men who also died of cardiac manifestations of Emery-Dreifuss muscular dystrophy. MEASUREMENTS: Post-mortem gross pathologic and histopathologic study of the heart. RESULTS: All three hearts showed a unique pattern of pathologic findings. Marked loss of atrial myocardium had occurred. Myocardium had been replaced by adipose and fibrous tissue. The conduction system showed no significant abnormalities. Varying degrees of interstitial and replacement fibrosis were present in the ventricular myocardium. CONCLUSIONS: Emery-Dreifuss muscular dystrophy is associated with characteristic pathologic changes in the heart that can cause death in female carriers and affected men. Female carriers should be identified and evaluated because of the risk for sudden cardiac death. PMID- 8215003 TI - Subcutaneous morphine for dyspnea in cancer patients. PMID- 8215004 TI - Comparing the status of women and men in academic medicine. AB - OBJECTIVE: To explore the status and academic productivity of women compared with men in academic internal medicine. DESIGN: Mail survey done in 1986. SETTING: A total of 107 major teaching hospitals in the United States. PARTICIPANTS: Full time (1693 of 2510) faculty in cardiology, rheumatology, and general internal medicine; 67% of eligible men and 70% of eligible women. MEASUREMENTS: Academic productivity defined as research grants awarded, abstracts accepted, and papers published in refereed journals; academic advancement as determined by academic rank and tenure status; and monetary compensation. RESULTS: Women entered academic medicine with shorter periods of fellowship training and were less likely to be members in the Alpha Omega Alpha honor society, but they had job descriptions similar to those of men, with similar allocation of work between research, clinical, and teaching activities. After adjustment, women and men were similar in the numbers of research grants funded as principal investigator (1.9 compared with 2.0), abstracts accepted (6.8 compared with 6.1), and papers published in refereed journals (28.8 compared with 29.2; all with P > 0.20). Women were as likely as men to have tenure, but they had lower academic rank (full or associate professor; 33% compared with 47%, P < 0.001) and received less compensation ($72,000 compared with $79,600 annually; P < 0.001). CONCLUSION: Although women do similar professional tasks and achieve similar levels of academic productivity, they receive fewer rewards for their work, both in academic rank and monetary compensation. PMID- 8215005 TI - Gastrointestinal cytomegalovirus disease. AB - OBJECTIVE: To describe the pathogenesis of gastrointestinal cytomegalovirus (CMV) disease, the types and locations of gastrointestinal lesions, the clinical settings in which they occur, and the specific methods available to diagnose and treat the disease. DATA SOURCES: Relevant English-language articles were identified through a MEDLINE search from 1985 to 1992. Articles referenced in the bibliographies of these articles and others were searched by hand. STUDY SELECTION: All articles that documented the occurrence of gastrointestinal CMV infection in humans, based on the finding of typical cytomegalic cells in histologic specimens, were selected for review. DATA EXTRACTION: Studies were grouped by content pertaining to pathogenesis, clinical setting, gastrointestinal location, diagnosis, or treatment. DATA SYNTHESIS: Gastrointestinal CMV disease is an erosive or ulcerative process that can occur at any location in the gastrointestinal tract, from mouth to rectum. Cytomegalovirus infection of columnar epithelial cells, endothelial cells, myocytes, and fibroblasts causes tissue destruction and ulceration. Serious CMV disease most frequently occurs with immune deficiency, such as the acquired immunodeficiency syndrome, after organ transplantation, after cancer chemotherapy, and after steroid therapy. Symptoms and signs depend on which part of the gastrointestinal tract is involved. Diagnosis depends on a positive mucosal biopsy that shows the presence of CMV by histopathologic or other techniques. In patients with persistent immune deficiency, progressive intestinal disease and death are frequent. Treatment with ganciclovir or foscarnet often heals intestinal lesions. CONCLUSIONS: Internists should be aware of the various clinical settings and locations in the gastrointestinal tract in which CMV disease occurs. Patients with immune deficiency and gastrointestinal signs and symptoms should have imaging tests and mucosal biopsies to investigate the possibility of CMV intestinal disease. Treatment with antiviral chemotherapy improves outcome in many patients. PMID- 8215006 TI - HIV lessons. PMID- 8215007 TI - The Clinton health care plan: fundamental or incremental reform? PMID- 8215008 TI - Fluconazole prophylaxis in patients with leukemia. PMID- 8215009 TI - Fluconazole prophylaxis in patients with leukemia. PMID- 8215010 TI - Isolating Borrelia burgdorferi from erythema migrans. PMID- 8215011 TI - The missing macroglobulin. PMID- 8215012 TI - Thrombolytic therapy for acute myocardial infarction in actively menstruating women. PMID- 8215013 TI - Worsening of neurocardiogenic syncope by beta-blockers. PMID- 8215014 TI - Community-based HIV trials are rigorous, says NIH. PMID- 8215015 TI - Insulin-like growth factors. AB - The purpose of this review has been to emphasize, in general terms, the major aspects of the structure, expression, and regulation of the IGF-I and IGF-II genes. The complex organization of these genes provides ample opportunities for control of gene expression at multiple levels. It is important to realize that regulation at one level can influence regulation at a different level. While such regulatory interactions are characteristic of both the IGF-I and IGF-II genes, they are particularly evident in the case of IGF-I gene expression. For example, the choice of transcription start site influences the length and the sequence of the 5'-UTR, which can influence mRNA translatability and prepeptide sequence, which may influence the amounts of protein produced and, potentially, the intracellular processing and secretion of the final gene product, the mature hormone. Another example is provided by the alternative splicing of E-peptide encoding exons, which determines the primary structure of the prohormone, which could influence its processing, stability, or function. Thus, this complex gene organization may reflect the need to carefully control, through a multilevel process, the synthesis, processing, and secretion of these important regulatory peptides. PMID- 8215016 TI - Somatotroph insulin-like growth factor-I signaling. PMID- 8215017 TI - Transport of insulin-related peptides and glucose across the blood-brain barrier. PMID- 8215018 TI - The role of the insulin-like growth factor system in neuronal rescue. PMID- 8215019 TI - Expression of insulin-like growth factor-I in transgenic mice. AB - The studies reviewed above provide strong evidence for the concept that IGF-I plays an essential role in mediating the growth-promoting actions of GH, and thus, they support the central elements of the "somatomedin hypothesis." The data, however, also point to actions of each GH and IGF-I that are not linked. Many hormones and factors, other than GH, are known to regulate the expression of IGF-I, as well as its binding proteins (modulators of its actions), in a tissue specific fashion. Some of these influences, e.g., estrogens, thyroid hormone, and nutritional factors, also effect GH synthesis and/or secretion. This complex and precise regulation undoubtedly plays a key role in coordinating the somatic and visceral growth stimulated by GH and IGF-I. The evidence that GH and IGF-I actions are not always coupled, therefore, is not surprising. The challenge is to dissect the precise role(s) of GH and IGF-I, as well as other hormones and growth factors, in the control of growth. Study of transgenic animals provides a powerful way to approach these issues in vivo. These studies demonstrate that IGF I is capable of stimulating in vivo brain growth. The transgene IGF-I-stimulated increase in brain size appears to result both from an increase in cell number and, as demonstrated by Carson et al., from an increase in myelin content, which in turn may result from proliferation of oligodendrocytes. Other roles for IGF-I in brain growth and development, however, are possible and amply supported by numerous studies of brain-derived cultured cells (see other papers herein). Because IGF-I is normally expressed in brain, it seems reasonable to assume that the IGF-I-stimulated brain growth observed in these transgenic mice represents a response to IGF-I overexpression rather than a pharmacologic response that is not indicative of a normal IGF-I function. Study of this IGF-I transgenic line cannot address the developmental period(s) when IGF-I normally stimulates brain growth, but this transgenic line provides a model to investigate IGF-I's specific role and its mechanisms of action. PMID- 8215020 TI - Insulin-like growth factors and nerve regeneration. PMID- 8215021 TI - Regulation of peripheral nerve regeneration by insulin-like growth factors. PMID- 8215022 TI - The biological role of truncated insulin-like growth factor-1 and the tripeptide GPE in the central nervous system. PMID- 8215023 TI - The potential of insulin-like growth factor-I as a therapeutic for the treatment of neuromuscular disorders. PMID- 8215024 TI - Activity-sensitive signaling by muscle-derived insulin-like growth factors in the developing and regenerating neuromuscular system. AB - In the nervous system, activity-sensitive retrograde signaling pathways couple the status of postsynaptic activation to elimination of collaterals during development and collateral sprouting in the adult. This article presents evidence supporting the hypothesis that in the neuromuscular system, skeletal muscle fiber derived insulin-like growth factors play a central role in such signaling. This evidence includes (1) timing and activity-sensitive expression of IGFs in skeletal muscle fibers, (2) identification of an IGF- and activity-sensitive retrograde signaling pathway from developing muscle to motoneurons in the spinal cord, (3) demonstration that IGFs in the muscle are both sufficient and necessary to induce interstitial cell proliferation and intramuscular nerve sprouting in adult muscle. PMID- 8215025 TI - The use of insulin-like growth factor I in the prevention of vincristine neuropathy in mice. PMID- 8215026 TI - Chronic morphine decreases insulin-like growth factor-I levels in the ventral tegmental area of the rat brain. PMID- 8215027 TI - Comparison of protein synthesis in brain and peripheral tissue during aging. Relationship to insulin-like growth factor-1 and type 1 IGF receptors. PMID- 8215028 TI - Chronic peripheral hyperinsulinemia induced by a variety of mechanisms fails to alter hypothalamic IGF-II receptor binding. PMID- 8215029 TI - Reversibility of serum removal effects on IGF-II mRNA in human neuroblastoma cells. PMID- 8215030 TI - Insulin, but not insulin-like growth factor-I, is expressed during early nervous system development in prepancreatic Xenopus embryos. PMID- 8215031 TI - Pharmacology of nerve growth factor output by target cells. PMID- 8215032 TI - Insulin-like growth factor-II in developing murine cerebellum. PMID- 8215033 TI - Trophic effects of melanocortins on neuronal cells in culture. PMID- 8215034 TI - Pituitary and peripheral insulin-like growth factor-I regulation by thyroid hormone. PMID- 8215035 TI - Effects of insulin and insulin-like growth factor-2 on the in vitro regeneration of the frog sciatic nerve. PMID- 8215036 TI - Inactivation of the IGF-I gene in mice results in perinatal lethality. PMID- 8215037 TI - IGF-I stimulates chick sympathetic neuron proliferation in vitro and in vivo. PMID- 8215038 TI - IGF-I-induced c-fos and c-jun expression in bovine chromaffin cells in primary culture. PMID- 8215039 TI - IGF-I supports the survival and/or differentiation of multiple types of central nervous system neurons. PMID- 8215040 TI - rhIGF-I enhances functional recovery from sciatic crush. Time-course and dose response study. PMID- 8215041 TI - Effects of multiple subcutaneous doses of rhIGF-1 on total and free IGF-1 levels and blood glucose in humans. PMID- 8215044 TI - Nerve growth factor as a neurotrophic agent. PMID- 8215043 TI - Patterns of insulin-like growth factor and IGF receptor gene expression in the brain. Functional implications. PMID- 8215042 TI - Regulation of oligodendrocyte development and central nervous system myelination by insulin-like growth factors. AB - In summary, our studies show that IGFs are potent regulators of oligodendrocyte development and myelination in vitro and in vivo. IGFs act at several levels: by promoting proliferation of oligodendrocytes and oligodendrocyte precursors, by inducing immature oligodendrocyte precursors to develop into oligodendrocytes, and by regulating myelin gene expression and the amount of myelin produced per oligodendrocyte. Our findings indicate that IGFs play a crucial role in normal oligodendrocyte development and myelination, and suggest that IGFs may have applications for the promotion of remyelination in myelin disorders such as MS. PMID- 8215045 TI - Insulin, neuropeptide Y, and food intake. PMID- 8215046 TI - Insulin and IGF-I receptor signaling in cultured neurons. AB - The data presented in this chapter are summarized in the schematic shown in Figure 9. Insulin binds to and stimulates autophosphorylation of neuronal insulin receptors, whereas, IGF-I and IGF-II binds to and stimulate autophosphorylation of neuronal IGF-I receptors. IGF-II is also capable of binding to the insulin receptor. Whether or not it activates the insulin receptor kinase remains to be clarified. Activated insulin and IGF-I receptor kinases phosphorylate a 70-kDa protein at early times in culture. This protein may mediate some actions of insulin, but we speculate that there are other intermediary proteins involved in the transduction pathway resulting in the activation of S6 kinase and PKC epsilon. The stimulation of S6 kinase by insulin and IGF-I may be associated with the translational activation of protein synthesis by these peptides. The stimulation of PKC epsilon appears to be a necessary step in the transcriptional regulation of the c-fos gene by insulin and IGF-I. The regulation of neuronal protein synthesis at a translational step and the initiation of transcriptional programs regulated by AP-1 represent two mechanisms by which insulin and IGFs alter neuronal growth and differentiation. PMID- 8215047 TI - Salivary diagnosis: promises, promises. PMID- 8215048 TI - Salivary macromolecules. A structure/function synopsis. AB - The status of our structure/function studies is at a crossroad. Further studies are needed to understand events on a molecular level, particularly how saliva is made and processed. Animal models as well as tissue and cell culture systems are being developed to address these issues. Nevertheless, enough information is now available to begin enhancing the natural defense properties of salivary secretions through clinical modalities such as the development of (1) diagnostic reagents and tests for local and systemic disease, (2) artificial salivas for the treatment of salivary dysfunction, and (3) topical vaccines to combat against oral diseases. PMID- 8215049 TI - Factors influencing the saliva/plasma ratio of drugs. PMID- 8215050 TI - Steroid hormone analysis in human saliva. AB - Despite the aforementioned complications, noninvasive saliva collection has provided the medical and research community with an excellent medium for the monitoring of plasma steroid levels. This noninvasive method has permitted the evaluation and assessment of a multitude of endocrine studies that would have been extremely difficult, if not impossible, using other more familiar methods. PMID- 8215051 TI - Status report on measurement of salivary estrogens and androgens. PMID- 8215052 TI - Measurements of salivary progesterone. PMID- 8215053 TI - Salivary testosterone measurements in behavioral studies. PMID- 8215054 TI - Saliva as a manifestation of the common mucosal immune system. PMID- 8215055 TI - Practical applications for saliva in perinatal HIV diagnosis. PMID- 8215056 TI - Significance of salivary antibody in dental disease. PMID- 8215057 TI - Simple and reliable salivary tests for HIV and hepatitis A and B virus diagnosis and surveillance. PMID- 8215058 TI - Salivary monitoring in oral diseases. PMID- 8215059 TI - The role of salivary measurements in the diagnosis of salivary autoimmune diseases. PMID- 8215060 TI - Mechanisms of fluid secretion by salivary glands. PMID- 8215061 TI - Plaque-mediated disease. Basic and clinical studies on the value of salivary monitoring. PMID- 8215062 TI - Considerations in the development of diagnostic tests on saliva. PMID- 8215063 TI - Development of a prototype, rapid saliva test for hepatitis B surface antigen (HBSAg) utilizing a "dipstick" method. PMID- 8215064 TI - A new device for collection of parotid saliva. PMID- 8215065 TI - Relationship of parotid saliva C-reactive protein to catecholamine release. PMID- 8215066 TI - Cystatin C levels of whole saliva are increased in periodontal patients. PMID- 8215067 TI - Biochemical changes in (glyco)proteins of saliva of epileptic patients. PMID- 8215068 TI - Effect of postmenopausal estrogen treatment on some diagnostic salivary variables. PMID- 8215069 TI - Anti-hepatitis A in the general population and in hepatitis A vaccinees using saliva and serum as diagnostic media. PMID- 8215070 TI - Quantitative determination and comparison of ethanol in saliva samples of unknown volumes with blood ethanol levels in human test subjects following ethanol ingestion. PMID- 8215071 TI - What accounts for the interindividual variability of sIgA concentration in saliva? PMID- 8215072 TI - Pleomorphy of individual protein patterns and cyclic AMP reactions in human saliva. PMID- 8215073 TI - Saliva and dental caries risk assessment. PMID- 8215074 TI - Protein composition, IgG, and IgA analysis in the saliva of patients with multiple sclerosis. PMID- 8215075 TI - Methods of simplified saliva collection for the measurement of drugs of abuse, therapeutic drugs, and other molecules. PMID- 8215077 TI - A bilateral collection device for noninvasive monitoring of drug levels in parotid saliva. PMID- 8215076 TI - HIV antibody EIA and western blot assay results on paired serum and saliva specimens. PMID- 8215078 TI - Salivary excretion of anticancer drugs. PMID- 8215079 TI - Applicability of saliva as a diagnostic fluid in Sjogren's syndrome. PMID- 8215080 TI - Detection of cotinine in oral fluid recovered with the OraSure collection system. PMID- 8215081 TI - Diagnosis of hepatitis A, B, and C using oral samples. PMID- 8215082 TI - Therapeutic drug monitoring using oral samples collected with the OraSure device. PMID- 8215083 TI - Detection of antibodies to Helicobacter pylori using oral fluid specimens. PMID- 8215084 TI - Pharmacokinetic principles of drug distribution in saliva. PMID- 8215085 TI - Clinical correlates of drugs in saliva. PMID- 8215086 TI - New approaches to monitoring environmental neurotoxins. PMID- 8215087 TI - Methods for collecting saliva. PMID- 8215088 TI - Fundamental principles involved in developing a new saliva-based diagnostic test. PMID- 8215089 TI - The role of saliva in drug monitoring. PMID- 8215090 TI - Saliva testing for drugs of abuse. AB - Saliva testing for drugs of abuse can provide both qualitative and quantitative information on the drug status of an individual undergoing testing. Self administration by the oral, intranasal, and smoking routes often produces "shallow depots" of drug that contaminate the oral cavity. This depot produces elevated drug concentrations that can be detected for several hours. Thereafter, saliva drug concentrations generally reflect the free fraction of drug in blood. Also, many drugs are weak bases and saliva concentrations may be highly dependent upon pH conditions. These factors lead to highly variable S/P ratios for many of the drugs of abuse. Table 3 provides a compilation of experimental and theoretical S/P (total) ratios determined for drugs of abuse. Estimations of the theoretical S/P (total) ratios for acidic and basic drugs were based on the Henderson-Hasselbalch equation. Saliva pH was assumed to be 6.8 unless reported otherwise by the investigators. Generally, there was a high correlation of saliva drug concentrations with plasma, especially when oral contamination was eliminated. Assay methodology varied considerably, indicating that saliva assays could be readily developed from existing methodology. There are many potential applications for saliva testing for drugs of abuse. Table 4 lists several general areas in which information from saliva testing would be useful. Clearly, saliva drug tests can reveal the presence of a pharmacologically active drug in an individual at the time of testing. Significant correlations have been found between saliva concentrations of drugs of abuse and behavioral and physiological effects. Results indicate that saliva testing can provide valuable information in diagnostics, treatment, and forensic investigations of individuals suspected of drug abuse. It is expected that saliva testing for drugs of abuse will develop over the next decade into a mature science with substantial new applications. PMID- 8215091 TI - Tussometry: an objective assessment of vocal cord function. AB - A number of techniques have recently been developed for altering laryngeal function, including structural framework surgery, reinnervation procedures, augmentation of the vocal cords, electrical stimulation, and pharmacologic intervention. The application of such procedures to appropriate disorders would be facilitated by better objective measures of the outcome. This study describes the new technique of tussometry, which investigates the airflow pattern produced during coughing. The value of 1 parameter, peak value time, is shown by a study of 35 vocal cord palsies versus a control, and of 17 vocal cord palsies before and after augmentation, to be an accurate assessment of vocal cord position. The technique is independent of lung function parameters and intraoral pressures. It is truly objective, having an interobserver variation of 0%, and is eminently reproducible, with an intrasubject coefficient of variation of 3.1% to 5.7%. Tussometry is a rapid, noninvasive technique providing inexpensive objective assessment of vocal cord function in the office setting. PMID- 8215092 TI - Teflon granulomas and overinjection of Teflon: a therapeutic challenge for the otorhinolaryngologist. AB - We have found that Teflon granulomas and the overinjection of Teflon with the resulting laryngeal dysfunction, although uncommon, present a challenge to the otorhinolaryngologist, due in large part to the inflammatory reaction to the injected Teflon. This report addresses the management of 16 patients (12 women and 4 men) treated surgically for symptoms secondary to Teflon granulomas or vocal folds that had been overinjected with Teflon. The presenting symptoms varied and included airway obstruction, cough, choking, swallowing difficulties, and dysphonia. In each case the granuloma and Teflon were removed endoscopically via a lateral cordotomy. A second procedure to address dysphonia due to vocal cord lateralization was frequently required and presents the challenge for the surgeon to select the appropriate procedure and time of intervention. The results of this retrospective review suggest that resolution of inflammatory changes and fibrosis subsequent to Teflon removal requires significant lengths of time and that thyroplasty techniques provide a means for medialization without reintroduction of the original inflammatory material. PMID- 8215093 TI - Outcome of open surgical therapy for glottic carcinoma. AB - A retrospective review was undertaken of the medical records of 270 patients with carcinoma of the glottic larynx. Patients were staged pathologically, and clinical pathologic correlates were made with outcome. In 92 patients with early glottic cancer, the 2-year rate of no evidence of disease for T1 was 98%, and for T2, 84%. Vertical partial laryngectomy resulted in voice preservation in 89%. Patients treated for advanced (T3 or T4) glottic carcinoma underwent total laryngectomy with or without neck dissection. Cervical nodes were involved in 22% of T3 and 41% of T4 patients at the time of treatment. Survival with no evidence of disease was chiefly determined by the development of regional recurrence, distant metastasis, and new primary cancer. Distant metastasis was associated with extracapsular spread (p = .003). Patients treated for T4 glottic carcinoma with neck dissection had improved survival compared with patients treated with laryngectomy alone (p = .006). Improved survival must be aimed at regional control, prevention, and management of distant metastasis and new primary carcinoma. PMID- 8215094 TI - Vocal granuloma, including sclerosis of the arytenoid cartilage: radiographic findings. AB - Vocal granulomas are uncommon benign tumors that may not respond readily to medical treatment or surgical removal. Gastroesophageal reflux is said to be a causative factor. Osteosclerosis of the arytenoid cartilage was found on computed tomographic scan in a series of 21 consecutive patients. The relationship of vocal granuloma to so-called contact ulcer (better called contact pachydermia) is discussed. Imaging of the granuloma and the arytenoid has little, if any, place in management, but should be recognized in the differential diagnosis of a vocal cord mass if the mass lies immediately adjacent to a sclerotic arytenoid. PMID- 8215095 TI - Effect of tension, stiffness, and airflow on laryngeal resistance in the in vivo canine model. AB - This study used an in vivo canine model of phonation to determine the effects of airflow on glottal resistance at low, medium, and high levels of recurrent laryngeal nerve (RLN) and superior laryngeal nerve (SLN) stimulation. Static and dynamic trials of changing airflow were used to study the effects of airflow on glottal resistance during phonation. As reported previously, glottal resistance varies inversely as a function of airflow. Increasing levels of RLN stimulation resulted in a statistically significant increase in glottal resistance for each level of airflow evaluated. Variation in SLN stimulation had no statistically effects on the relationship between flow and resistance. At airflow rates greater than 590 milliliters per second (mL/s), glottal resistance approached 0.1 mm Hg per mL/s for all levels of RLN and SLN stimulation tested. These data support the collapsible tube model of phonation. PMID- 8215096 TI - Function of the thyroarytenoid muscle in a canine laryngeal model. AB - Fundamental frequency is controlled by contraction of the thyroarytenoid (TA) and cricothyroid (CT) muscles. While activity of the CT muscle is known to tense and thin the vocal folds, little is known about the effect of the TA muscle on vocal fold vibration. An in vivo canine laryngeal model was used to examine the role of the TA muscle in controlling phonation. Isolated TA muscle activation was obtained by stimulating sectioned terminal TA branches through small thyroid cartilage windows. Subglottic pressure measures, electroglottographic and photoglottographic signals, and acoustic signals were obtained in 5 mongrel dogs during dynamic and static variations in TA muscle activity. Results indicated that TA muscle activation is a major determinant in sudden shifts from high frequency to modal phonation. Subglottic pressure increased and open quotient decreased gradually with increasing TA activation. PMID- 8215097 TI - Air pulse quantification of supraglottic and pharyngeal sensation: a new technique. AB - There are no published studies evaluating the sensory capacity of the region innervated by the superior laryngeal nerve. A normal sensory capacity is important in this area, since hypesthesia or anesthesia of the pharynx and supraglottic larynx may result in dysphagia and aspiration. This often occurs after stroke or after ablative surgery of the pharynx and larynx. Evaluating the efficacy of restorative procedures for supraglottic and pharyngeal sensation is dependent on defining and quantifying the sensory deficit. We have developed a new, noninvasive method to measure sensation in the pharynx and supraglottic larynx. A puff of air--of precisely controlled duration and pressure--was delivered via a flexible telescope to the anterior wall of the pyriform sinus. Surface sensibility was determined according to the psychophysical method of limits by varying air pressure while holding puff duration constant. We conducted 204 trials in 20 healthy adults. The average sensory discrimination threshold was 2.09 +/- 0.15 mm Hg. An intraclass correlation revealed excellent consistency (R = .80). There was no statistically significant difference between the right and left sides. Brief air pulse stimulation is an easy, relatively safe, and reliable method of determining supraglottic and pharyngeal sensory discrimination thresholds. PMID- 8215098 TI - Hair relaxer ingestion: a new trend. AB - Although the health care system has done much to reduce the incidence of ingestion of such alkalis as drain and oven cleaners, in recent years we have seen an overwhelming increase in the incidence of hair relaxer ingestion. In a 5 year review (1987 to 1992) of 48 cases of caustic ingestion, 15 cases involved alkaline hair-relaxing agents. This retrospective study was undertaken to evaluate the agents ingested, the presenting signs and symptoms, the diagnostic procedures, and the outcomes in those 15 cases. Oral cavity and lip burns were common in these children, but none of the 15 had significant esophageal burns. Education of the medical and lay community about the risk of hair relaxer ingestion should be undertaken to reverse this worrisome trend. PMID- 8215099 TI - Dedifferentiated chondrosarcoma of the larynx with regional and distant metastases. AB - Chondrosarcoma of the larynx is an unusual tumor, with only approximately 200 cases having been reported. This tumor is relatively nonaggressive and tends to remain localized in the larynx. Two cases with aggressive clinical behavior manifested by regional or distant metastasis are presented. In the first case, cervical node metastasis appeared 6 months after total laryngectomy. A dedifferentiated chondrosarcoma was identified by pathologic examination. In the other case, clavicular metastasis developed 7 years after initial local excision. Despite additional treatments, the patient later developed cervical node, lung, and vertebral metastasis. Transformation from low-grade to dedifferentiated chondrosarcoma was verified by pathologic examination. We believe this case to be the first reported laryngeal chondrosarcoma with bone metastasis. A review of the literature regarding regional and/or distant metastasis of laryngeal chondrosarcoma, including the present observations, reveals a total of 20 cases. In all cases, tumor grade has been directly correlated with the development of metastasis. PMID- 8215100 TI - Voice rehabilitation after total laryngectomy and tracheoesophageal puncture using nonmuscle closure. AB - The successful production of voice with a tracheoesophageal puncture (TEP) and voice prosthesis requires a compliant pharyngoesophageal segment. Speech failure is commonly attributed to spasm of the pharyngoesophageal segment. During total laryngectomy (TL), a 3-layer closure is typically performed. This prospective single-arm study examines the safety and efficacy of TL and TEP with nonclosure of the pharyngeal musculature to prevent pharyngoesophageal spasm as an alternative to 3-layer closure with pharyngeal plexus neurectomy and/or pharyngeal constrictor myotomy. Twenty-one consecutive patients were enrolled by a single surgeon. The mean duration of follow-up was 19.5 +/- 7.9 months. Surgical complications and voice rehabilitation outcomes were examined. An overall complication rate of 28.5% was observed. Fluency was achieved in 75% of patients within a mean of 4.3 +/- 5.1 months. Speech failure was attributable to early primary site and neck recurrence (5%), hypoglossal nerve palsy (5%), hypopharyngeal stricture and recurrence (5%), dementia (5%), and intransigent alcohol abuse (5%). Pharyngoesophageal spasm was not observed in any subjects. We conclude that primary TEP with nonclosure of the pharyngeal muscle during TL is relatively safe. Furthermore, it is preferable over 3-layer closure because it avoids pharyngoesophageal spasm, a factor limiting voice rehabilitation. PMID- 8215101 TI - Positron emission tomography of auditory sensation in deaf patients and patients with cochlear implants. AB - The present study investigated the function of the auditory cortices in severely hearing-impaired or deaf patients and cochlear implant patients before and after auditory stimulation. Positron emission computed tomography (PET), which can detect brain activity by providing quantitative measurements of the metabolic rates of oxygen and glucose, was used. In patients with residual hearing, the activity of the auditory cortex measured by PET was almost normal. Among the totally deaf patients, the longer the duration of deafness, the lower the brain activity in the auditory cortex measured by PET. Patients who had been deaf for a long period showed remarkably reduced metabolic rates in the auditory cortices. However, following implantation of the cochlear device, the metabolic activity returned to near-normal levels. These findings suggest that activation of the speech comprehension mechanism of the higher brain system can be initiated by sound signals from the implant devices. PMID- 8215102 TI - Early-stage development of auditory center: an experimental study of auditory evoked electrophysiologic recordings from fetal and newborn guinea pigs. AB - Five guinea pig fetuses at 8 weeks' gestation (term is 9 weeks) were tested for auditory brain stem response (ABR) generated by earphones placed outside the maternal abdomen. The results obtained from these fetuses were compared with the ABRs in 10 term newborn guinea pigs on the 1st and 20th day after delivery. The ABRs indicated a decreasing peak latency over wave III with increasing age. The interpeak latency to wave III-V decreased markedly, with very little change in wave I-III. The results suggested rapid maturation of the upper brain stem and midbrain during late gestation and in newborns. They also exhibited an increasing peak latency of ABRs from both fetuses and newborns with decreasing stimulus intensity. PMID- 8215103 TI - Growth rate of acoustic neuroma expressed by Ki-67 nuclear antigen versus symptom duration. AB - The growth rate of acoustic tumors varies widely. An immunohistochemical study with Ki-67 monoclonal antibody was performed on a random sample of 21 acoustic neuromas. The tumors belonged to 2 well-defined groups: 1 with a short duration of preoperative symptoms (< 1 year) and 1 with a long duration of preoperative symptoms (> 5 years). The tumors were of small to medium size (7 to 27 mm), and no large, cystic, or Recklinghausen tumors were included. The tumor proliferative fraction expressed by monoclonal antibody Ki-67 was determined. The results revealed a significant relation between the tumor proliferative fraction and symptom duration. Tumors with a high proliferative status had a short preoperative symptom duration, while tumors with a low proliferative status had a long symptom duration. The clinical implications of these results are discussed. PMID- 8215104 TI - Recurrent laryngeal nerve paralysis during transvenous insertion of a permanent endocardial pacemaker. AB - We present 2 patients with sudden onset of dysphonia due to acute unilateral vocal cord paralysis that occurred during transvenous insertion of a permanent endocardial pacemaker. Acute paralysis of the vocal cord due to this kind of medical intervention is a very unusual complication that has been rarely reported. We believe that traumatic insertion of a pacemaker through the subclavian vein triggered a dynamic process that led to vocal cord paralysis. Three hypothetic explanations are presented: 1) a direct vagus nerve lesion, 2) a direct inferior laryngeal nerve lesion, and 3) a central nervous system lesion caused by a cerebral microembolus. Physicians should be aware of the possibility that associated acute paralysis of the vocal cord may occur after transvenous insertion of an endocardial pacemaker. PMID- 8215105 TI - Dexamethasone inhibition of the development of dysplastic bony lesions in LP/J mice. AB - Inbred LP/J mice have been observed to spontaneously develop abnormal bony lesions of the ossicles and otic capsule that progress throughout the life of the animals. This genetically inherited murine disorder produces bony lesions that share some gross and histologic features with bony lesions seen in human tympanosclerosis. Previous studies on LP/J mice have demonstrated evidence of immunologically mediated injury in the progression of the newly forming bony lesions. This study was designed to examine the effects of dexamethasone on the development of the bony lesions in LP/J mice. The purpose was to attempt to elucidate the relationship of the immunologic injury observed in earlier studies and the progression of the dysplastic bony lesions. The results show that LP/J mice treated with dexamethasone developed significantly fewer dysplastic bony lesions compared to the age-matched, saline-treated controls. There was also a statistically significant difference in the quantity and cellularity of the middle ear effusions between the experimental and control animals. PMID- 8215106 TI - Unilateral acoustic neuroma associated with a tenth cranial nerve schwannoma. PMID- 8215107 TI - Fibrosarcoma of the posterior neck. PMID- 8215108 TI - Squamous odontogenic tumor. AB - The squamous odontogenic tumor is almost exclusively an intraosseous lesion of the jaw bones. Only 1 extraosseous variant has been reported. The tumor is histologically benign, with only occasional recurrences after surgical removal. Malignant alteration is unknown, but the lesion must be distinguished from intraosseous squamous cell carcinomas. PMID- 8215109 TI - Monophyletic origin of the genus Leishmania Ross, 1903. PMID- 8215110 TI - [Observation in France of Simulium erythrocephalum De Geer, 1776 as an agent of human simuliidosis]. AB - Second observation of this black-fly in human simuliidosis. The country is the department of Vaucluse. PMID- 8215111 TI - [Nomenclature of Strongylidae above the family group]. AB - It is necessary to distinguish the three main evolutionary lines which presently constitute the Trichostrongyloidea. We propose to raise the following taxa of Strongylida as presented in the CIH keys (1974). Ancylostomatina for Diaphanocephaloidea and Ancylostomatoidea. Strongylina for Strongyloidea. Trichostrongylina for Trichostrongyloidea. Metastrongylina for Metastrongyloidea. The Trichostronglyina suborder includes three superfamilies: Trichostrongyloidea, Molineoidea superfam. nov. and Heligmosomoidea superfam. nov. PMID- 8215112 TI - Change of isoenzyme pattern during long-term polyxenic cultivation of Entamoeba histolytica. AB - Isoenzymes of phosphoglucomutase and hexokinase were repeatedly evaluated using starch gel electrophoresis in polyxenic cultures of Entamoeba histolytica. In two out of 18 strains spontaneous changes of isoenzyme patterns were recorded. While originally they were categorized into virulent group of zymodemes, following isoenzyme analysis classified them as non-virulent. The relation between virulence and isoenzyme pattern is questionable. PMID- 8215113 TI - [Contribution to the study of Microphallidae travassos, 1920 (Trematoda). XLV. Description of Maritrema feliui n. sp., parasite of shrews (Mammals) in Spain]. AB - The authors describe and illustrate the morphology of the adult stage of Maritrema feliui n. sp. (Trematoda Microphallidae) obtained from the intestine of the shrew Crocidura russula (Hermann, 1780), definitive host of the fluke present in the estuary of the river Llobregat (Catalonia, Spain). The larval stages are found in two hosts obtained from the area: 1) Mercuria confusa (Frauenfeld) [= Pseudamnicola similis (Draparnaud)] (Mollusca: Hydrobiidae), and 2) Gammarus aequicauda (Martynov) (Crustacea: Amphipoda). The adult stage is anatomically related to the Maritrema with a mean size of the body, two equal suckers, a short oesophagus and long caeca, and a short and transversal cirrus pouch with a smooth and filiform cirrus. According to morphological and geographical affinities, the authors propose the synonymies of 1) Maritrema "opisthometra" sensu Bridgman et al., 1972 with M. chiriacae Deblock, 1975; 2) Maritrema longiforme Kifune et al., 1972, with Maritrema laricola Ching, 1963. Besides Maritreminoides congjiangensis Chiu et Gu, 1981 is transferred into the genus Quasimaritrema Deblock, 1973 according to Maritreminoides Rankin is invalidated. PMID- 8215114 TI - [Study by the immunofluorescence reaction of antibodies directed against antigens of the gut epithelium of Schistosoma mansoni. V. Modulation of granulomatous reaction around the egg under the influence of an IgM monoclonal antibody]. AB - The periovular granulomatous reaction has been reduced in vivo by an IgM monoclonal antibody. The granulomatous reaction has been obtained either in unsensitized, or sensitized as well as immunized mouse. The granulomatous reduction could be explained by a decrease in egg viability, owing to the fact that the monoclonal antibody is lethal against an in vitro miracidium suspension. PMID- 8215115 TI - Human bilharzial ureters. II. Cellular dynamic against deposited eggs. AB - The cellular dynamic against deposited Schistosoma haematobium eggs was studied in the submucosa and muscularis of the lower ureteral segments of Saudi patients with chronic urinary schistosomiasis. This dynamic activity was greatly affected by the damaged phase of the egg embryo. Freshly deposited eggs with "healthy" embryos were entirely surrounded by long cytoplasmic extensions of fibroblasts. Eggs with partially damaged embryos were surrounded by plasma cells which were focally adhered to spines of egg-shells and releasing their granular contents over their surface. Eggs with "dead" embryos, or empty egg-shells, were surrounded by actively mobile macrophages possessing numerous lysosomes, phagocytic vacuoles, and convoluted surface projections. After "peeling" off the outer and intermediate shell layers, macrophages invaded into eggs and fused together forming multinucleate giant macrophages. This study showed that the fibroblastic extensions acted as barriers between the parasite eggs or their products, and the host tissue; the plasma cell secretion over the egg surface may be involved in the migration of macrophages towards deposited eggs; and macrophages were the only dynamic cells responsible for the egg-shell invasion possibly for elimination. PMID- 8215116 TI - Effect of ivermectin on two filaria-vector pairs. Brugia malayi-Aedes aegypti; Litomosoides sigmodontis-Bdellonyssus bacoti. AB - The effect of ivermectin was studied on two filaria-vector pairs, Brugia malayi Aedes aegypti and Litomosoides sigmodontis-Bdellonyssus bacoti. The rodent hosts, respectively Mastomys coucha and Meriones unguiculatus, were treated with ivermectin doses of 0.05 mg/kg, or 0.2 mg/kg or 2 mg/kg. Batches of vectors were fed on rodents, infected or not, treated or not, from H7 to D43 post-ivermectin. Vector survival was observed and dissections were performed to study the filarial development. It appears that ivermectin has no systemic effect on vectors, or very little. The drug acts on transmission because it affects the microfilariae. Transmission of L. sigmodontis is blocked because microfilariae are eliminated from the blood. Transmission of B. malayi is blocked although microfilaremia remains present at a low level. Two particular features are observed: microfilariae are hyper-ingested, but they do not cross the stomach wall (in contrast, they cross at a high rate in the control batch of Aedes, due to the "stomach wall limitation"). These events might be explained by a muscular passivity of the microfilariae treated with ivermectin. Transmission of the two filarioid species is restored normally about D25-40 post ivermectin because a new population of microfilariae has appeared. These ivermectin experiments emphasize the diversity and complexity of two important phases of the filarial cycle in the vector: the ingestion of microfilariae and the passage through the stomach wall. PMID- 8215117 TI - [Appreciation of the evolution of the price of drugs in Rouen from 1640 to 1788]. AB - 34 accounts of medicines found in the rolls of "Maitrise Notre-Dame" of Rouen were studied. Data concerning clysters, ptysans, violet sirup, theriac, marsh mallow paste and physic were particularly collected. Their interpretation showed a relative stability of the market prices of drugs and medicines, expressed in pounds, during a century and a half, in Rouen. PMID- 8215118 TI - [Current challenges for the pharmaceutical research industry]. AB - The Research Pharmaceutical Industry is currently facing a number of increasingly complex challenges. Today indeed, the discovery and marketing of innovative medicines is linked: not only to Compagnies' abilities to solve relatively basic and traditional difficulties which have deeply changed over the past few years, for instance: the regulatory constraints, the dramatic increase in development costs, the critical mass required for investments, the development time periods and the protection of innovation, human resources and organization; but also to the acceptance of recent factors which the Research Pharmaceutical Industry must imperatively overcome, such as: the new Research channels and namely biotechnologies, the building of a pharmaceutical Europe and the internationalization of molecules, the needs of the third world, the innovation financing and the control of Health expenditures, the public opinion's shift in expectations regarding ethical and environmental issues. The Pharmaceutical Industry is currently in a shake-up phase during which it will undergo deep changes, with regard both to its activities and in relations with its environment. PMID- 8215119 TI - [Multiparameter approach to undesirable effects of drugs that may represent risk for the automobile driving]. AB - Drugs part in traffic accidents is not well known. We attempted to specify it taking out of pawn the adverse effects which could be liable: drowsiness; consciousness lose; dizziness; eye-sight troubles; hallucinations, hearing troubles; drunken feelings, behaviour modification; propensy to suicide, interference with alcohol. Drugs involving such effects were indexed; their therapeutic indications and their chemical structure were taking into account. Statistical classical count allowed us to quantify relative importance of this ten adverse effects category. Multivariate analysis worked out structuration this undesirable effects into 97 different profiles by the mean of the Minimum Spanning Tree method and established proximity links between the 409 active principles recorded. This results are reported here. PMID- 8215120 TI - [Synthesis and pharmacological activity of ethyl N-acetic and N-malonic esters of heterocyclic derivatives]. AB - The pharmacological study of heterocyclic N-ethylacetic and N-ethylmalonic esters indicate a stimulating effect on central nervous system. Some derivatives show antidepressive and psychostimulant activities. PMID- 8215121 TI - [Decontamination of some spices by ethylene oxide. Development of 2-chloroethanol and ethylene glycol during the preservation]. AB - After the disinfection by ethylene oxide and storage by ethylene oxide in definite conditions of 16 spices (parsley, chervil, tarragone, chive, thyme, rosemary, coriander, nutmeg, mace, cinnamon, allspices, clove, pepper), the authors observed the fast loss of residual ethylene oxide and ethyleneglycol. On the contrary, the persistence of 2-chloroethanol was followed up for 6 months. They turn their attention to the toxicity of this compound to ensure the protection of customers. PMID- 8215122 TI - [Action mechanism of L-dopa: dopaminergic activation or glutamatergic inhibition?]. AB - Since 25 years ago, it was postulated that the antiparkinsonian activity of L DOPA was due to the activation of the synthesis and the release of dopamine that it could trigger in the dopaminergic terminals preserved during the Parkinson's disease. Recent experimental data, presented in this paper could show that L DOPA, far from activate the nigro-striatal dopaminergic neurons, would rather inhibit them and that its antiparkinsonian action could be attributed to the antiglutamatergic activity that L-DOPA, converted to dopamine, could exert by acting on the D2 receptors of the striatal glutamatergic afferences. This antiglutamatergic action of L-DOPA would concern the NMDA as well as the non-NMDA receptors and it is therefore unlikely that the NMDA antagonists could be good anti-parkinsonian drugs (unless they would be coadministered with non-NMDA antagonists). Dopaminergic (D2) agonists could be interesting antiparkinsonian drugs all the more they could be devoid of the potentially neurotoxic properties of L-DOPA. PMID- 8215123 TI - A mechanical leech for transverse rectus abdominis musculocutaneous flaps. AB - Venous congestion in the intraoperative and postoperative period can be a problem with some transverse rectus abdominis musculocutaneous flaps. We evolved a technique to allow us the ability to bleed the congested flap in a controlled manner both intra- and postoperatively. Arteriotomy cannulae are placed within the lumens of the deep inferior epigastric artery (DIEA) and vein (DIEV) and they are brought out on the lateral aspect of the reconstructed breast. We believe that intermittent venous bleeding from the DIEV allows a congested flap time to improve venous outflow and adapt to the new reversed blood circulation. When laser Doppler flow meter is simultaneously used as a monitor, bleeding from the DIEV or DIEA can improve balance between arterial and venous pressure in the flap. PMID- 8215124 TI - Enhancing fibula free flap skin island reliability and versatility for mandibular reconstruction. AB - Although the fibula osteocutaneous free flap has many advantages when used in mandibular reconstruction, many investigators have found the skin island is not always reliable. We present a technique that enhances skin island reliability by including a maximal number of skin perforators. This method has been used in 10 consecutive osteocutaneous free flaps without any skin loss. This technique also expands the usefulness of the fibula free flap, allowing it to be used for shorter bone defects or in cases when skin coverage is needed at a distance from the bone. In addition, this method provides additional vascularized soft tissue for neck contour restoration and coverage of fixation plates. PMID- 8215125 TI - Use of split anterior tibial muscle flap in treating avulsion injury of leg associated with tibia exposure. AB - Avulsion injury of the leg may result in exposure of the anterior surface of the tibia in addition to skin loss. This exposed bone should be covered by a soft tissue flap to facilitate healing and provide durability. The split anterior tibial muscle flap is ideal in this situation because of its adjacent location, reliability, and simplicity. A cadaveric study demonstrated rich intramuscle vascular anastomoses between the segmental branches from the anterior tibial artery that provide safety in partial transfer. The technique of split anterior tibial muscle flap was applied successfully in 4 patients with leg avulsion injury associated with tibial bone exposure. The cosmetic result was good and the function of the muscle was preserved. PMID- 8215126 TI - Microvascular augmentation of the blood supply of the contralateral side of the free transverse rectus abdominis musculocutaneous flap. AB - The free transverse rectus abdominis musculocutaneous (TRAM) flap is a recognized, reliable method of breast reconstruction after mastectomy. However, blood supply to the contralateral side of both the free and pedicled TRAM flap, especially in zone four, is often precarious. In patients with previous midline abdominal scars or with significant rectus divarication, both zones three and four are at risk of necrosis. Various techniques have been described to improve the reliability of the blood supply to the contralateral tissue in the pedicled TRAM flap, including prior delay and microvascular supplementation. We describe a new technique for augmentation of the blood supply of the contralateral side by microvascular anastomosis of the distal end of the ipsilateral deep inferior epigastric vessels to a contralateral periumbilical perforator of the opposite side. This technique produces reliable survival of contralateral tissue in zones three and four, even in the presence of midline scars, with minimal damage to the contralateral rectus muscle. The technique is also beneficial where large bulk of tissue is needed, such as in radical mastectomy patients, or when abdominal tissue is thin but the normal breast is large. Five patients in a series of 50 free TRAM flaps have been treated with the technique and the results are compared with other techniques. PMID- 8215127 TI - Mandible fragment fixation during reconstruction: the splint-and-plate technique. AB - One of the most popular methods of mandible fragment fixation is the precontoured reconstruction plate technique. Unfortunately, this method is not a reliable option when tumor distorts the mandibular contour or extends through the buccal cortex of the mandible. An alternative to the precontoured reconstruction plate is the splint-and-plate technique of mandible fragment fixation. An application of this appliance and method in 10 patients revealed the technique's advantages. The splint can be applied quickly and does not obstruct the ablative or reconstructive procedure. Further, the splint accurately keys the dentition and reliably maintains temporomandibular joint relationships. Finally, this technique provides a reference point to the exact position of the symphysis and angle when these landmarks have been resected. PMID- 8215129 TI - Crotalidae envenomation in children. AB - Poisonous snakebites cause a severe envenomation syndrome in children, yet treatment remains controversial. Sixty-seven patients were treated for poisonous snakebites at our institution between 1975 and 1990; 18 were children < or = 12 years old. There were 13 rattlesnake bites, 4 copperhead bites, and 1 unidentified bite. Initial management included intravenous fluids and antibiotic administration, laboratory studies, tetanus prophylaxis, affected limb elevation, and a limited excision of the bite site in the emergency room. Antivenin was administered only if signs of systemic involvement such as shock, coagulopathy, gastrointestinal cramping, or neurological involvement were present. Children developed systemic involvement 72% of the time, 9 children (50%) developed coagulopathy. Consequently, 11 (61%) children received antivenin. The dose of antivenin they received was 3.2 ml/kg and the children tolerated it well with only 36% of them demonstrating adverse reactions to the antivenin. Clinically, the pediatric patients demonstrated signs and symptoms of a fulminant envenomation syndrome (8 days, average hospital stay), yet, they had a good eventual outcome. Only 11% of children reported long-term morbidity. No deaths occurred and 100% of patients were able to return to full preinjury activities. We conclude that Crotalidae envenomation in children is a serious disease and warrants hospitalization, early surgical involvement, and frequent use of antivenin. PMID- 8215128 TI - Tissue expansion in the pediatric patient. AB - Although tissue expansion has many advantages over other reconstructive options, potential complications require consideration. The purpose of this study was to evaluate the experience of tissue expansion in the infant and child. During the 6 year period from 1985 to 1990, a total of 147 expanders were placed in 76 patients. Age of the patients at the time of insertion of the expanders ranged from 1 to 18 years (median, 8 yr). Twenty of the 76 patients studied suffered from complications, a rate of 26%. Despite the high complication rate, complications did not compromise the final result because they occurred near the end of the expansion period and usually involved one of the many implanted expanders. With the appropriate selection of patients, tissue expansion has proved extremely valuable as a reconstructive option in the pediatric patient. PMID- 8215130 TI - Closure of mediastinal wounds with deepithelialized rectus abdominis musculocutaneous flaps. AB - Deep and narrow mediastinal defect after sternal debridement can be effectively obliterated by deepithelialized vertical rectus abdominis musculocutaneous flaps, based on the superior epigastric vessels. This composite flap has sufficient mass to obviate the need for additional vascularized tissue and is, therefore, offered as an alternative to multiple flap procedures. It offers a superior cosmetic appearance and better chest stability than a traditional island myocutaneous flap. Eleven patients had their mediastinal wounds repaired by this method with a low complication rate and good final results. PMID- 8215131 TI - Simultaneous inflatable penile prosthesis insertion and corporoplasty for septal chordee attributed to Peyronie's disease. AB - Impotent patients with Peyronie's disease who qualify for penile prosthesis surgery may pose a reconstructive challenge that can best be resolved at the time of exploration. Restrictive plaques, especially septal chordee, that persist after prosthesis insertion deserve resection. The surgical technique, pathophysiology, and management of postoperative edema facilitated by percutaneous access to the Resipump are described. PMID- 8215132 TI - Ear-piercing technique by using an eyelet-type Teflon piercer (Eyelet-Piercer). AB - We devised a new method of piercing earlobes. This method, in which an eyelet shaped Teflon tube (Eyelet-Piercer) is left in the earlobe continuously, is advantageous in that any type of pierced earrings the subject wishes can be used immediately after treatment and in that subjects with metal allergies can safely use pierced earrings. In addition, the incidence of complication was lower with this technique than with conventional methods that use metal earrings for piercing. PMID- 8215133 TI - Contraction rates of meshed, nonexpanded split-thickness skin grafts versus split thickness sheet grafts. AB - Contraction rates of wounds covered by meshed, nonexpanded split-thickness skin grafts were compared with split-thickness sheet-grafted wounds in a porcine model. No significant difference was found in wound contraction. When compared with previous studies, this study shows that differences in contraction previously observed were not a result of meshing and suggests that expansion may be the cause of the difference previously observed. PMID- 8215134 TI - Comparison of skin necrosis in rats by using a new microneedle electrocautery, standard-size needle electrocautery, and the Shaw hemostatic scalpel. AB - "Microneedle" electrocautery was compared against the standard-size needle electrocautery and the Shaw hemostatic scalpel to determine the differences in tissue necrosis when used as a cutting instrument. Incisions were made on the dorsal skin of anesthetized white rats using each of the three devices with the no. 15 scalpel as control. The specimens were submitted for histological evaluation. The microneedle caused less necrosis than the standard-size needle electrocautery (0.18 vs 0.27 mm, p < 0.01) and less necrosis than the Shaw hemostatic scalpel set at 220 degrees F (0.18 vs 0.25 mm, p < 0.05). The microneedle electrocautery was also found to be an instrument that causes very little tissue distortion during fine dissection and helps to minimize blood loss in craniofacial and neurosurgical operations. PMID- 8215135 TI - The combined tensor fasciae latae/rectus femoris musculocutaneous flap: a possibility for major soft tissue reconstruction in the groin, hip, gluteal, perineal, and lower abdominal regions. AB - A 57-year-old man, with a long-lasting multiple hereditary cartilaginous exostoses, presented with a progressive tumor growth in the left iliac wing and in the gluteus maximus muscle. An open biopsy revealed a secondary chondrosarcoma, which had developed from an osteochondroma. A wide surgical resection, sparing the inferior limb, was the option for treatment. The fairly constant and reliable vascular anatomy of the lateral circumflex femoral artery, as confirmed by 27 previous anatomical dissections, gave us the opportunity to repair the wide postoperative defect by means of a single, very large flap, combining the vascular territories of the tensor fasciae latae and rectus femoris musculocutaneous flaps. The postoperative period was uneventful, and 1 year after surgery the man had no sign of local recurrence or metastases, and the flap was fully viable without sign of local complication. A functional evaluation was performed on a Kin-Com II dynamometer, showing major impairment of the limb that had undergone surgery. Despite the severe functional disturbance, the man prefers the impaired status to an amputation after a hemipelvectomy. PMID- 8215136 TI - A combined anterolateral thigh flap, anteromedial thigh flap, and vascularized iliac bone graft for a full-thickness defect of the mental region. AB - A triple combined anterolateral thigh flap, anteromedial thigh flap, and vascularized iliac bone graft was used for reconstruction of a full-thickness defect of the mental region after wide resection of advanced tongue cancer. The distal end of the pedicle vessels of these double skin flaps, i.e., the lateral circumflex femoral system, was directly anastomosed in tandem to the pedicle of the iliac bone graft, which was enveloped by these flaps. The advantages of this iliac osteocutaneous flap are as follows: It can be transferred within a shorter surgical time because the flaps can be obtained in the supine position simultaneously with tumor resectioning; and its skin components can be separated from the bone because each component has its own pedicle vessels, has a longer vascular pedicle (> 10 cm), and has a thicker crest of the bone graft. This flap is believed to be suitable for reconstruction of large full-thickness defects in various sizes of the mandibular and maxillary regions of the face. PMID- 8215137 TI - The gluteus maximus superior split muscle flap for complex posterior pelvic wounds. AB - Coverage of complex posterior-lateral pelvic wounds can be difficult with currently described flaps. Using a superior transposition of the superior portion of the gluteus maximus, coverage can be obtained without resorting to free tissue transfers. No functional deficits are seen in ambulatory patients. We present a cadaver dissection and 2 patient reports to illustrate this versatile flap. Coverage of wounds involving the deeper aspects of the sacroiliac joint, or the posterior iliac crest, can be difficult without resorting to free tissue transfers. After trauma, osteomyelitis of these two areas can be treated by adequate and extensive debridement, but in doing so, significant dead space can be created. We have found the superior split gluteus muscle rotation flap to be an excellent choice in 2 patients whom we have encountered. To our knowledge, the superior rotation of this muscle flap has not been previously reported. PMID- 8215138 TI - A new osteotomy for genioplasty--stepped osteotomy: preliminary report. AB - A new osteotomy for genioplasty, stepped osteotomy, is described. This osteotomy is a combination of horizontal and sagittal osteotomy of the mandibular symphysis. It consists of horizontal osteotomy at a distance of 3 to 4 mm below the apexes of the anterior teeth, connecting at right angles with the conventional horizontal osteotomy below the mental foramen, making a step fashioned osteotomy of the chin. This procedure is particularly advantageous in simultaneous elongation and advancement genioplasty because the central portion between the apexes of the anterior teeth and the conventional horizontal osteotomy line is available as augmentation and the bony contact of the osteotomized mandible can be retained in elongating the chin. The characteristics of this procedure are described and typical patients are shown. PMID- 8215139 TI - "The blood-red blossom of war". PMID- 8215140 TI - High-energy war wounds: flap reconstruction. AB - In this article, we emphasize that knowledge of terminal ballistics is essential for understanding the pathophysiology of war wounds. We present our own experiences in treatment of high-energy war wounds in 75 patients treated in the Institute of Plastic and Reconstructive Surgery, Department of Surgery, Clinical Hospital Center in Zagreb. Patients were divided into three groups with regard to the time of definite reconstruction, using local or free microvascular flaps. About 12% of patients underwent flap reconstruction in the acute phase, associated with low complication rate and the shortest hospital stay. Group II was comprised by 18% of the patients and, considering the number of complications, presented the most unfavorable time for reconstruction. Flap reconstruction in the chronic phase resulted in a substantial prolongation of the hospital stay in 82% of patients. Therefore, we advocate proper primary treatment of wounds aimed at early flap closure. This type of management results in a significantly shorter hospitalization and leads to more effective rehabilitation and recovery of patients. PMID- 8215141 TI - Review of the perceptions of general surgical staff within the Wessex region of the status of quality assurance and surgical audit. AB - The opinion of surgical staff about the present state and effectiveness of surgical audit within a single regional health authority has been obtained by questionnaire. Seventy-five per cent of registrars/senior registrars and 72 per cent of consultants completed and returned the proforma. The majority of registrars (86 per cent) believe that it is vital or very important to collect clinical outcome information that is relevant, accurate and complete. However, more than half (56 per cent) felt that these objectives were not being met. All consultants also agreed with the statement that meaningful surgical audit and quality assurance must be based on confidential critical peer review of relevant, accurate, ongoing and complete information. None, however, believed that this objective was being met completely, while only 41 per cent felt that they were doing even 'fairly well', with the principle reason for failure being lack of time. These results support the view that most surgeons are keen to achieve meaningful audit, but at present this objective is not being satisfactorily met. PMID- 8215142 TI - Guidelines and standards in surgical training. PMID- 8215143 TI - Audit and research: complementary but distinct. PMID- 8215144 TI - Acute intestinal ischaemia: options in surgical management. AB - Seven patients (mean age 67 years, range 52-82 years) presented with acute intestinal ischaemia over a 4-year period. Massive bowel resection was performed in all patients. Exteriorisation and secondary restoration of intestinal continuity was employed in four patients. In two patients a primary anastomosis was performed at the time of resection and one patient underwent a 'second-look' procedure. Massive bowel resection and exteriorisation allows direct observation of stoma viability, avoids the risk of anastomotic breakdown and should be considered in all but moribund patients with acute intestinal ischaemia. In elderly patients resection and primary anastomosis may be an alternative option. PMID- 8215145 TI - A trauma centre in the UK. PMID- 8215146 TI - Trauma audit: clinical judgement or statistical analysis? AB - Comparisons have been made between two methods currently used to assess the effectiveness of management of major trauma. These are the review of fatal cases by senior clinicians and the use of statistical analysis of severity scores. The former was assessed by a re-examination of the Coroners' reports of 508 patients reviewed by senior clinicians at the request of The Royal College of Surgeons of England Working Party on the Management of Patients with Major Injuries. The latter was based on the 665 fatalities on the files of the UK Major Trauma Outcome Study. The two groups of patients had comparable age and sex profiles and broadly similar ranges of injury severity. There were major differences between and inconsistencies within the two assessments. Clinicians more frequently judged death avoidable in those with very severe injuries. In contrast, the statistical analysis suggested, paradoxically, that the proportion of avoidable deaths in those patients who had minor injuries was less than the proportion of avoidable deaths in those who had more serious injuries. These variations underline the limited values of retrospective peer review and will not encourage clinicians to adopt currently available statistical methods. Further refinements of anatomical and physiological scoring systems and their integration to provide a statistically valid and clinically acceptable measure of outcome are essential prerequisites to the wider introduction and success of trauma audit. PMID- 8215147 TI - An audit of peripheral nerve blocks for hand surgery. AB - A prospective audit of 140 median, radial and ulnar blocks, given for 70 hand operations is described. The surgery was completed successfully in every patient. A further injection of local anaesthetic was required in 13 operations. Four patients experienced severe tourniquet pain. The results of the audit have shown that if a careful technique is used, a wide range of minor hand operations can be performed under regional nerve block. PMID- 8215148 TI - Reduction in incidence of glove perforation during laparotomy wound closure by 'no touch' technique. AB - Intact surgical gloves provide an efficient barrier against the HIV and Hepatitis B viruses but glove perforations are common, particularly during mass closure of laparotomy wounds. Attempts to develop gloves immune to perforation have failed. A series of 100 consecutive laparotomy wounds were randomised to mass closure by either the 'hand in' technique currently favoured by many surgeons, or a 'no touch' technique manipulating the wound edges with instruments only. The two groups were similar with regard to grade of surgeon and assistant, proportion of routine and emergency cases, and proportion of clean or dirty cases. The wound lengths in each group were similar, and the time taken to close the abdominal wall was similar in both groups. Although a similar number of perforated gloves occurred in each group while the operative procedure was being performed ('hand in', 9 of 50 vs 'no touch', 12 of 50; P = 0.62); a significantly reduced number of glove perforations occurred in the 'no touch' group during wound closure ('hand in', 16 of 50 vs 'no touch', 3 of 50, P = 0.0017). No touch closure of the abdominal wall may provide protection to surgeons against blood-borne viruses such as HIV and hepatitis B. PMID- 8215149 TI - Blood contamination of the feet during orthopaedic procedures. AB - Contamination of the feet with blood represents a potential hazard for the surgeon. The incidence of such contamination during major orthopaedic surgery has been shown in this study to be 54%. The use of protective leggings during surgery is recommended. PMID- 8215150 TI - Physical status is the principal determinant of outcome after emergency admission of patients with colorectal cancer. AB - A prospective study of 825 consecutive patients with colorectal cancer presenting to three general surgeons in a district general hospital over a 10-year period are reported. In all, 735 patients had an operation and are grouped according to whether their operation was within 24 h of admission (n = 63), more than 24 h after admission (n = 151), or elective (n = 521). Operative mortalities for these groups were 15.9%, 15.2% and 6.5%, respectively, significantly higher in both the emergency groups. Delayed surgery to allow complete resuscitation did not improve the operative mortality when compared with those patients having urgent surgery. Both groups of emergency patients, delayed (27%) urgent (19%), showed poorer 5 year survival than the electively treated patients (36%), many dying of non cancer causes. Patients who undergo emergency surgery for colorectal carcinoma are more likely to be in poorer physical condition than patients undergoing elective surgery for the same condition. It appears that the physical status is the principal determinant of outcome after emergency colorectal surgery rather than any other factor. PMID- 8215151 TI - Factors influencing blood transfusion during adult liver transplantation. AB - From 1982 to 1990, 300 adults received liver transplants in Birmingham UK with a median intraoperative blood transfusion rate of 23.5 units for the first 50 patients falling to 8 units for the last 50. The major factors in the reduction of blood usage were the experience of the team, the use of venovenous bypass and the use of an argon beam coagulator. Univariate analysis of preoperative factors in an attempt to predict patients at risk of excessive intraoperative transfusion showed that levels of serum sodium, urea, creatinine, haemoglobin, patient weight and the presence of ascites were significantly related to the quantity of blood transfused, although stepwise discriminant analysis showed that only blood urea and platelet count had an independent association with transfusion. The final model was poorly predictive of intraoperative transfusion requirements. Technical factors rather than patient-related factors are more important in the control of intraoperative bleeding in newly established transplant programmes. PMID- 8215152 TI - Post-cholecystectomy symptoms after laparoscopic cholecystectomy. AB - Abdominal symptoms persist in up to 40% of patients after laparotomy cholecystectomy and biliary lithotripsy. Laparoscopic cholecystectomy is now the treatment of choice for symptomatic gallstone disease. However, no data exist as to the influence of laparoscopic cholecystectomy on symptoms. We analysed 100 patients who had undergone laparoscopic cholecystectomy at a median of 12 months (range 10-19 months) previously. Pre- and postoperative symptoms were compared and patient satisfaction was graded from 1 (best) to 5 (worst). Time to resumption of full activity (mean +/- SD) was recorded. All patients had more than two symptoms preoperatively. Postoperatively, 61 patients had complete absence of symptoms, 14 patients complained of only one symptom during the postoperative period and 25 patients continued to have at least two symptoms. The mean time taken to return to full activity was 2.4 +/- 1.7 weeks. In patients without any symptoms postoperatively, time taken to return to full activity was 2.3 +/- 1.5 weeks, 2.7 +/- 1.4 weeks for patients with one symptom postoperatively, while patients with two or more symptoms returned to full activity in 2.3 +/- 1.3 weeks and 2.6 +/- 1.7 weeks, respectively. Notwithstanding that 25% of patients reported two or more symptoms postoperatively, most patients (n = 84) considered the procedure to be a complete success. A further 10 patients had significant improvement after laparoscopic cholecystectomy. Five patients considered themselves only slightly improved, while a single patient was no better off postoperatively. These data indicate that after laparoscopic cholecystectomy most patients return to full activity within 3 weeks. Thus, the incidence of post-cholecystectomy symptoms is similar after laparoscopic and laparotomy cholecystectomy and biliary lithotripsy.Patients should be advised of the risk of persistent symptoms after these procedures. PMID- 8215153 TI - Investigation and significance of short saphenous vein incompetence. AB - In this study, 186 limbs with varicose veins or venous skin changes were examined using duplex ultrasonography. Limbs were classified on the basis of short saphenous or popliteal venous incompetence and the number of limbs with venous ulceration (active or healed) recorded. Short saphenous incompetence did not produce a significant increase in the incidence of ulceration, whereas popliteal reflux produced an increase in the risk of ulceration which was statistically significant when compared with limbs without reflux in these two veins (chi 2 = 4.55, P = 0.003). There was no significant difference in the proportion of limbs with concomitant long saphenous reflux between these two groups. Short saphenous reflux is not important in the pathogenesis of venous ulceration. Popliteal reflux is an important factor in the pathogenesis of venous ulceration. More attention should be paid to the surgical correction of popliteal reflux when present in limbs with venous ulceration that fail to heal by conservative measures. PMID- 8215154 TI - Case mix and outcome of patients referred to the vascular service at a district general hospital. AB - A prospective audit has been carried out to evaluate the trends in case mix and initial management of vascular surgical referrals to a single surgeon at a district general hospital. Over a 3-year period there were 1096 new emergency or routine referrals from a population of approximately 450,000. A total of 613 of these patients underwent vascular procedures, with a further 297 procedures subsequently being undertaken on the same patients during the period of the audit. There was a steady increase in the total number referred with little change in case mix with regard to age or diagnosis. Elderly patients had more severe symptoms and were less likely to be treated by minimally invasive means. The number of patients undergoing angioplasty or thrombolysis increased steadily without any corresponding reduction in the number of surgical procedures. It is concluded that there is a steady trend towards increasing vascular surgical workload which is not easily explained by a change in disease incidence or case mix. Elderly patients appear unlikely to be referred unless symptoms are severe and there are few referrals of elderly patients who might benefit from minimally invasive treatments. PMID- 8215155 TI - Oesophageal perforation after button battery ingestion. PMID- 8215156 TI - From flint to stainless steel: observations on surgical instrument composition. AB - Man's failure to extract deeply embedded thorns and arrowheads, with bare hands and teeth, stimulated 'instrument substitutes' mimicking these appendages. Evidence from primitive communities suggest animal, plant and mineral items were employed, both before and after metal became the standard material of today's armamentarium. Changing surgical instrument composition has mirrored concurrent technology and manufacturing methods both of which are reviewed. Particular significance is accorded flint, bronze, crucible steel, thermal sterilisation, nickel-plate, stainless steel and disposable plastics. The paper is based on an exhibition From Flint to Stainless Steel on display at the College. PMID- 8215157 TI - Comparison of 'intraoperative' parathormone measurement with frozen section during parathyroid surgery. PMID- 8215158 TI - Strap muscles in thyroid surgery: to cut or not to cut? PMID- 8215159 TI - Strap muscles in thyroid surgery: to cut or not to cut? PMID- 8215160 TI - [Celioscopic surgery and law about the protection of persons in biomedical research]. PMID- 8215161 TI - [Intraductal carcinoma of the breast (DCIS). Should the treatment be conservative or not?]. AB - Due to systematic mammography, DCIS is being seen with increased incidence than in the past. Asymptomatic women screened by mammography show a high incidence of microcalcifications. Lymph node involvement is seen in very few patients. Total mastectomy provides local control and long term survival approaching 100%. Immediate breast reconstruction allows better acceptance of mutilations. Conservative treatment has been advocated for localised DCIS. The classification system dividing DCIS into comedo- and non-comedo subtypes could be an oversimplification because of the frequent histological heterogeneity. Other criteria such as cytological features oncogene activity of C erb 2 and clinical and radiological features must be considered. It has now been demonstrated that DCIS does not have a multicentric distribution. Assessment of lesion size appears to be primordial for breast conservative treatment indications. A relationship has been demonstrated between lesion size and microinvasion. The aim is complete excision with free margins and a cosmetically acceptable postoperative result. Radiotherapy seems to lower the incidence of local recurrences in retrospectives studies. Prospective randomized trials are being conducted to compare lumpectomy with and without radiotherapy. PMID- 8215162 TI - [When will we stop mastectomies for intraductal carcinoma?]. AB - There has been growing interest in intraductal carcinomas of the breast (DCIS) over the last ten years mainly because of their increasing frequency and their difficult diagnosis. Their natural history is often surprising. For the time being, it is impossible to establish which proportion of DCIS might turn into an infiltrating carcinoma, and which factors are predictive for such a risk. These uncertainties are responsible for many controversies about their treatment. Based on a critical review of the latest publications, this paper deals with the possibilities of conservative treatment, challenging the remarkable results of total mastectomy (nearly 100% survival at 10 years). The risk of conservative treatment depends on the frequency of local recurrence, and on the potential vital risk of such recurrences, knowing that half of these recurrences will develop in an invasive, and no longer in situ, pattern. Randomized trials are being conducted on this question; they will not give an answer before the year 2000. In the mean time, conservative treatment seems to be reasonable for small low grade histologic lesions widely excised by surgery, and with rigorous possibilities of follow-up. The operation is followed by external irradiation. In case of recurrence, mastectomy has to be. It is not impossible that, performed under these conditions, a slight increase in mortality might follow such a strategy, thus heavily balancing the benefits of conserving the breast. Besides, surgical excision alone should only be performed as part of randomized trials, or for infra-centimetric lesions discovered by histology after resection of supposed benign lesions. PMID- 8215163 TI - [Transjugular portacaval shunt. Preliminary experience]. AB - Transjugular intrahepatic portosystemic stent-shunt (TIPS) is a new technique in interventional radiology. This procedure is based on the creation of an intrahepatic channel between a main branch of the portal vein and an hepatic vein. A metallic stent is implanted to keep this shunt patent. From July 1990 to March 1992, 28 out of 32 patients with a history of gastric or esophageal variceal rebleeding, were treated by TIPS and followed for up to 20 months (mean 9.36 +/- 5.42). According to the Child Pugh's classification, 9 patients had class A cirrhosis, 17 class B and 6 class C. TIPS led to reduction of the portal pressure gradient by 57% and improvement of the portal blood flow by 250%. Early complications were: one technique-related death due to a medial stent implantation on the portal bifurcation (massive extrahepatic bleeding), other cases consisted of hemobilias (3 patients), intra-abdominal bleeding (1 patient) and gastrointestinal bleedings (4 patients). All of the complications except the deat were spontaneously reversed after withdrawal of Heparin. Follow-up showed a considerable improvement of ascites, seen in 55% of the patients with 100% reduction or disappearance after 3 months. Duplex-sonography follow-up found shunt stenosis in 43% of the patients, allowing preventive redilatation to restore patency of the shunt. Variceal rebleeding occurred in 20% of cases. These results remain interesting with regard to the high risk of bleeding in the patients of this preliminary study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215164 TI - [Cancers of the stomach and peritoneal carcinoses: will hyperthermia be a new therapeutic approach?]. AB - Overall survival rate of gastric adenocarcinoma is poor whatever the therapeutic is. Main reasons for this poor prognosis are regional failure and local recurrences. Using hyperthermia could be of interest in peritoneal carcinomatosis during gastric carcinoma: in vitro cytotoxic effect of hyperthermia is well known. Using hyperthermia in combination with intra peritoneal chemotherapy could improve local control. Preliminary results of pilot studies treating peritoneal carcinomatosis with intra peritoneal chemohyperthermia are reported. PMID- 8215165 TI - [Pancreatic endocrine tumors: contribution of ultrasound endoscopy in the diagnosis of localization]. AB - Endoscopic ultrasonography is a new imaging technique which has previously demonstrated its accuracy in localization of small pancreatic cancers. The aim of this retrospective study was to report our experience of this new method for localization of small endocrine tumors of potential pancreatic origin. Thirteen patients with insulinoma and 17 patients with Zollinger-Ellison syndrome were studied. All were imaged in a reference center by ultrasound (US) and CT scan (CT) before endoscopic ultrasonography. Insulinomas: 78.5% of tumors were 15 mm or less in size. The endoscopic ultrasonography was more accurate (79%) than US (7%) and CT (14%) for localization of the 14 tumors removed in the 13 patients who underwent surgery. Gastrinomas: Endoscopic ultrasonography was able to image 7 to the 9 pancreatic gastrinomas, the 2 duodenal gastrinomas, and the 2 gastrinomas located in peripancreatic lymph nodes which were removed in the 9 patients who underwent surgery. US and CT were able to image only one of the two peripancreatic lymph nodes. We concluded that endoscopic ultrasonography is a highly accurate tool for localization of small pancreatic endocrine tumors and should be performed early in the management of these tumors. PMID- 8215166 TI - [Requirement for thoracotomy in thoracic trauma]. AB - With intensive care, pleural drainage and judicious physiotherapy most thoracic injuries can be treated adequately. 571 patients were treated for severe thoracic injuries over the last 10 years. A thoracotomy was necessary in 14% of the patients with blunt trauma (BT) and 33% with penetrating trauma (PT). Thoracotomy for PT was performed earlier and had better results than thoracotomy for BT. Seventy-five percent of PT were operated in the first hour after admission against 29% of BT. Postoperative mortality for PT was three times lower than for BT (18% vs 56%). Reasons for this are the higher rate of injuries associated with BT. Surgical procedure depends on the type and extent of the thoracic and general injuries and on the patient's general condition. PMID- 8215167 TI - [Partial splenectomy requiring ligation of splenic vessels. Apropos of 40 cases]. AB - Conservative treatment of the spleen is generally based on segmental terminal vascularization of the spleen. The practise of partial splenectomies in the case of major trauma and hilar hydatid cyst led us to perform subtotal splenectomies after splenic vessel ligation. The upper pole splenic remnant after reduction of its volume, remains vascularized by other short vessels through the gastro splenic ligament. The lower pole splenic remnant remains vascularized by the left gastro-epiploic artery. The follow-up of 40 subtotal splenectomies performed in these conditions revealed better results than those obtained after spleen autotransplantation in the omentum. Conservation of all the vessels of the gastro epiploic ligament allows gastric transposition of the spleen. PMID- 8215168 TI - [Cysto-hepatic ducts; surgical consequences. Apropos of 29 cases]. AB - Cysto-hepatic ducts are a rare entity constituting less than 2% of biliary tract operations. Twenty-nine cases have been encountered in our General Surgical Service between 1980 and 1989. The frequency is about 2.3% in a series of 1,265 operative and/or postoperative cholangiographies analysed during the same period. Cystohepatic ducts were discovered in 3 cases at dissection, in 10 cases on operative cholangiography, in one case after biliary tract lesion, and in 15 cases on postoperative cholangiography. The cystohepatic duct was voluntarily or involuntarily respected in 23 cases, voluntarily ligated in one case, involuntarily in 2 others, cut and drained outside in one case, injured and repaired in one case, and cut in another. From our experience, we conclude that the roles of dissection of the cystic duct and the recognition of well known biliary bifurcation do not permit in all cases to avoid common bile duct lesions, particularly in the presence of an unforeseeable and dangerous variant such as a cystohepatic duct draining a large hepatic territory. As a result, the first stage of cholecystectomy should not be dissection of the biliary bifurcation, ligation of the cystic duct and its intubation but especially dissection of all elements of Budd's triangle before intubation of the supposed cystic duct. This avoids leaving upstream from the sectioned cystic duct, an hepatic territory not drained by the common bile duct. A good quality systematic operative cholangiography reveals in the other cases this anatomical variant and constitutes an essential medico-legal document for the patient's and surgeon's safety. PMID- 8215169 TI - [Neoplastic transformation of a cyst in the thyroglossal tract. Apropos of a case]. AB - Cancers of the thyroglossal tract are very rare. Seventy-four patients with a cyst of the thyroglossal tract were operated in our hospital between 1978 and 1991. A papillary carcinoma was discovered on histological examination in one case. This cancer was treated by Sistrunk's operation. The patient had no sign of recurrence one five years after the operation. This paper presents the case report of this unusual cancer of which fewer than 100 similar cases have been reported in the literature. PMID- 8215170 TI - [Loco-regional anesthesia for surgery of limbs]. AB - This article is a review of recent data concerning: plexus and peripheral nerve blocks for the upper and lower limbs, intravenous regional anesthesia, and medullary, epidural and spinal anaesthesia. We have focused on the advantages and disadvantages of each technique which should be taken into account for their selection. Regional anaesthesia techniques are not without risks, and advantages are perhaps not as obvious now as was reported in the past, especially in the case of medullary spinal or peridural anaesthesia. PMID- 8215172 TI - [Parietal dissemination of carcinoma of the gallbladder after celioscopic surgery]. AB - A case of tumor seeding in an abdominal trocar hole after laparoscopic extraction of an incidental gallbladder carcinoma is reported. The high incidence of occult tumors of the gallbladder and appendix warrants caution when dissecting and extracting operative specimens. PMID- 8215171 TI - [Volvulus of the transverse colon. Apropos of three cases]. AB - Volvulus of the transverse colon is a very rare entity, representing 1 to 3.4% of all volvuli of the colon. We report three cases illustrating the problems of this pathology. The presentation is usually acute, leading to prompt surgery. Multiple etiologies may be combined: congenital malrotations of the gut, chronic constipation in the elderly enhanced by psychiatric medications, and mechanical by adhesion bands which help to create anomalous rotation axes for the volvulus. The best treatment must be surgical, and we recommend an aggressive approach: an extended right colectomy, which gave good results in our patients. PMID- 8215173 TI - [Guide to writing film scripts to improve the quality of didactic medical videotapes]. PMID- 8215174 TI - [Antibiotic prophylaxis in adults in surgical units. Paris, 10-11 December 1992]. PMID- 8215175 TI - [Colorectal cancer in patients over the age of 80 years]. AB - Between January 1, 1973 and December 31, 1986, 1.734 patients underwent colorectal resections for carcinoma. The patients were divided into two groups: group I included 163 patients > 80 years on first presentation; group II comprised 1.571 patients < 80 years. The total perioperative mortality rates of the elderly and younger group were 15.3 percent and 5 percent respectively (p < 0.001). The surgical mortality rates in group I were 7.4 percent after elective operations versus 4.5 percent in group II and were not statistically different. Emergency surgery was associated with a significantly higher incidence of perioperative deaths at any age (p < 0.001). In the elderly group, most deaths (88%) resulted from complications of coexisting medical disorders or thrombo embolic complications. The 5 year survival for the young and elderly groups were 46.2 percent and 35 percent respectively (p < 0.05). However, excluding patients dying from nonmalignant disease, the 5 year survival rate did not differ significantly between the two groups of patients (49.5 percent versus 42.2 percent). PMID- 8215176 TI - [Celioscopic treatment of acute obstructions of the small intestine. Immediate results in 25 patients]. AB - Laparoscopic treatment of small intestinal obstruction is associated with immediate advantages and it may be expected that the recurrence rate will be decreased because of the reduction of wound scars. Between september 1989 and september 1991, 25 patients (16 men and 9 women), mean age 53.8 years, underwent initial laparoscopy for acute small intestinal obstruction. These patients had undergone a total of 43 (1.7 per patient) laparotomies an average of 13 years previously. One patient had never been operated on, 13 had one previous laparotomy, five had two, four had three, and two had four previous laparotomies. Laparoscopic treatment of intestinal obstruction was possible in nine cases including three cases of bands and six cases of adhesions. In sixteen cases, laparoscopy had to be completed by laparotomy, 13 immediately and 3 secondarily. The cause of immediate failure was the impossibility of finding and/or treating the cause in seven instances, four cases of intestinal wounds, on case of intestinal necrosis which required resection, and one case of missed right colonic carcinoma. The cause of secondary failure were incomplete release of adhesions, volvulus, and missed left colonic carcinoma in one case each. Mean hospital stay and postoperative ileus were significantly shorter in the "laparoscopy" group than in the laparoscopy + laparotomy group (p < 0.001). Two complications, with one death, were noted in the laparoscopy + laparotomy group. In conclusion, laparoscopic treatment of intestinal obstruction seems possible but in less than half of cases. Failures are related to the difficulty with which the abdomen may be explored. Laparoscopic treatment should not be pursued in case of problems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215177 TI - [Celioscopic appendectomy. Results in 137 consecutive patients]. AB - Between September 1990 and August 1992, laparoscopic appendicectomy was attempted in 137 patients: 98 females and 39 males (sex-ratio: 2.5:1) with a mean age of 31 years (range: 15-85). The patients were operated on by 9 surgeons. Laparoscopic appendicectomy was possible in 120 patients (87.6%). In 19 patients the procedure was converted into open surgery. The main causes of unsuccessful laparoscopic procedures were: retrocaecal appendix (n = 5) and injury of appendiceal artery (n = 4). The rate of unsuccessful procedures was 31% in retrocaecal appendix and 9.4% in the other cases (P < 0.02). In exclusively laparoscopic procedures, the mean operating time was 63 (2.9) minutes. It was 49 (3) minutes for experienced surgeons and 69 (3.3) for other surgeons (P < 0.05). Histological examination of the appendix revealed inflammatory signs in 97 specimens (71%). There were no wound infections after successful laparoscopic appedicectomy. One female patient developed an abscess in the pouch of Douglas. The median postoperative hospital stay was 3 days (range: 1-16). These results suggest that laparoscopic appendicectomy is a safe technique, with low morbidity allowing short postoperative hospital stay. PMID- 8215178 TI - [Obstruction of the small intestine caused by adhesions after appendectomy. Argument for repeated surgery as proposed by Mac Burney]. AB - After appendectomy, mechanical obstruction of the small intestine is often due to local bands. This type of obstruction is classically treated by median laparotomy. We present ten cases of such obstruction treated via the initial gridiron incision, whose advantages are discussed. PMID- 8215179 TI - [Hydatid cyst of the liver. Treatment by resection of the cyst wall. Our experience apropos of a series of 495 cases]. AB - From January 1976 to December 1990, 495 cases of hydatid cyst of the liver were treated by resection of the cyst wall. The mean age of the patients was 42 years with a female predominance (71% of cases). Confirmation of the diagnosis was essentially based on ultrasonography. At operation, the hydatid cysts were located in the right lobe of the liver in 83% of cases. The hepatic dome (segments VII + VIII) was involved in 52% of cases. After resection of the cyst wall, biliary tract lesions required common bile duct drainage with a Kehr drain in 50 cases, transcystic drainage in 22 cases and cysto-biliary disconnection in 22 cases. In every case, drainage of the residual cyst cavity was performed by a two-way catheter. Seven deaths were recorded in this series, including one from anaphylactic shock associated with intracystic injection of formalin, 3 from bronchopulmonary complications, 2 from subphrenic abscesses and 1 after surgical revision for evisceration on the 5th day. The postoperative morbidity and, consequently, the hospital stay depended on the condition of the pericystic tissues. The mean hospital stay was 12 days in the case of soft pericystic tissues and 32 days in the case of fibrotic and calcified pericystic tissues. Due to the benign nature of hydatid cysts of the liver, the authors emphasise the value of resection of the cyst wall which carries a lower operative risk and which can be performed by most surgeons. PMID- 8215180 TI - [Is your scalpel correctly adjusted? The correct use of electric scalpels in digestive system endoscopy]. AB - Progress has been made in electric scalpel technology, as applied to endoscopy, over recent years. Lamp or spark gap scalpels have been replaced by more reliable transistor scalpels fitted with a return electrode avoiding any defective circuits. Before using an electric scalpel, it is essential to understand the basic physical laws governing their use with section, coagulation or mixed currents. Any interference with other electrical apparatuses in the surgical endoscopy room must be avoided and precautions must also be taken in patients with cardiac pacemakers. Different settings are required for colonic polypectomy and endoscopic sphincterotomy in order to ensure a clean cut without oedema and with perfect haemostasis. Although monopolar currents are generally used, some haemostatic or tumour destruction electrodes use a bipolar current which avoids deep necrosis. Diathermy is a precise technique in interventional endoscopy, but surgeons must adapt their knowledge to the equipment used. PMID- 8215181 TI - [External iliac lymphadenectomy by celioscopy: surgical technique]. AB - A complete description is provided of all the various operating steps for external iliac laparoscopic lymphadenectomy. The umbilical artery is easy to identify via laparoscopy and immediately provides the internal boundary for node excision. Laparoscopic vision also enables the other boundaries to be located, that is, the obturator nerve to the bottom and the iliac external and internal bifurcation towards the top. Examination of the nodes thus removed provides a means of assessing the spread of malignancy from cervical and uterine cancers, using a codified operation which can be included during staging or complete cancer surgery. PMID- 8215182 TI - [Biliary surgery using the ligamentum teres. Technique for repairing loss of substance in the common bile duct]. AB - Ligamentum teres was used to repair a total or partial common duct defect in seven cases: 4 cases of biliobiliary stone fistula, 2 cases of hydatid cysto biliary fistula and one case of iatrogenic common bile duct trauma. Biliary duct reconstruction is possible in the above cases of biliary damage. The short-term and long-term results were satisfactory. PMID- 8215183 TI - [Giant cell chondroma of soft tissues. Apropos of a case and review of the literature]. AB - Soft tissue chondroma is a benign cartilaginous tumour most often located at the extremity of the upper limbs. We report a very unusual case of soft tissue chondroma due to its location in the sole of the foot resulting in delayed diagnosis. Diagnosis of soft tissue chondroma was confirmed by microscopic examination and by immunohistochemistry showing S 100 protein in the cells of mature and immature areas. The presence of numerous giant cells is exceptional. Labelling of the giant cells by KP 1 protein in the present case suggest that they are derived from macrophages. PMID- 8215184 TI - [Arterial complications of arthroscopic meniscectomies. Apropos of three cases]. AB - The authors report three exceptional cases of vascular lesions occurring during arthroscopic meniscectomies involving the posterior horn of the lateral meniscus. These lesions consisted of false aneurysms of the popliteal artery detected early (1 month) or later (5 months and 3 years) after the procedure, one of which formed a fistula with the accompanying vein. This later case resulted in intermittent claudication of the calf and the other two cases presented with painful flexion deformity of the knee. In the case diagnosed after 1 month, the false aneurysm arose from a punctate injury to the artery and was treated by direct arterial suture. In the other two cases, treatment consisted of excision of the false aneurysm and restoration of arterial continuity by an autologous saphenous vein graft. The quality of the clinical result was confirmed angiographically in all three cases. The anatomy predisposes to this complication which can be avoided by respecting a few simple precautions. The surgeon must be avoided by respecting a few simple precautions. The surgeon must be aware of and look for signs of this complication in order to allow early diagnosis. PMID- 8215185 TI - [Abdominal cystic lymphangioma in children]. AB - Cystic lymphangioma is a rare tumour (6% of benign tumours in children), frequently situated in the cervical or axillary region and exceptionally intraabdominal. It arises due to a congenital defect in the connection of the primary lymphatic channels with the central collecting system. It presents clinically either in the form of a pseudo-appendix or pseudo-ascites syndrome or in the form of an abdominal tumour with or without compression of adjacent structures. It can now be easily diagnosed by ultrasonography. Treatment is well defined and consists of surgical resection of the isolated lymphangioma or associated with the adjacent intestine, depending on the site of the tumour. It has a good prognosis. PMID- 8215186 TI - [Aneurysm of the splenic artery: an uncommon etiology of segmental portal hypertension]. AB - A patient presented with gastrooesophageal varices secondary to splenic vein compression by a splenic artery aneurysm. Splenectomy and aneurysm resection ensured a good clinical result and disappearance of the segmental portal hypertension. PMID- 8215187 TI - [The cost of a surgical videotape and its financing]. PMID- 8215188 TI - The decade of the brain. PMID- 8215189 TI - Treatment of symptomatic vasospasm with nimodipine. AB - Over a seven-year period, 130 patients with delayed ischaemia after cerebral aneurysm haemorrhage were treated with intravenous nimodipine. The delay from the last haemorrhage to the appearance of ischaemic symptoms was one to 18 days, and vasospasm was confirmed in most cases. Nimodipine treatment was started within three days of delayed ischaemic deficit (DID) onset, at a low dose increased quickly to 30-45 ug/kg/hr, and reduced gradually over the last day or two of the course. The duration of treatment was one to 27 days. Side effects were minor, and serious complications few. Hypotension occurred in 35 cases. During treatment, there were highly significant improvements in both clinical grade and Glasgow Coma Score. The final outcome was 98 good (Glasgow Outcome Score 1), 18 permanent deficits (eight GOS 2, ten GOS 3), and 14 dead. Ischaemia was directly involved in only half the deaths. These results are much better than the natural history (about 1/3 dead and 1/3 disabled), and a considerable improvement over fluid and hypertensive treatment (17% dead, 29% deficits), calculated from a literature review. Nimodipine is also safer than induced hypertension, especially pre-operatively. PMID- 8215190 TI - Posterior fossa extradural haematoma--experience of nineteen cases. AB - Twenty-four cases of posterior fossa extradural haematoma constituted 4.16% of all extradural haematomas (576) and 1.12% of all craniocerebral trauma requiring surgery (2150). Five cases were excluded from this study. Of the remaining nineteen cases (the study group), lucid interval was present in eight (42.10%) cases. In half of the cases, the clinical course was acute. Neck stiffness and drowsiness were the commonest clinical signs. Occipital bone fracture was present in 57.89% cases. CT scan was the most valuable investigation in the diagnosis and detection of the associated intracranial injury in 18 cases. Associated intracranial injury was present in seven (36.84%) of these cases. Two (11.1%) of these patients died despite emergency surgery. The Glasgow Coma Scale prior to operation and the presence of associated supratentorial injuries were important prognostic factors. It is concluded that posterior fossa extradural haematoma should be suspected in the presence of a fall on the back of the head, drowsiness, neck stiffness or an occipital bone fracture. PMID- 8215191 TI - Failed back surgery syndrome: problems, pitfalls and prevention. AB - Several basic and fundamental principles remain prime considerations in lumbar spine surgery, so a review of these is appropriate in view of the current headlong rush into the use of new and developing technology for lumbar spine surgery. Eighteen hundred and sixty-one laminectomy procedures are reviewed, the majority of these for simple lumbar disc protrusion and spinal canal stenosis but also 204 cases where patients required a surgical procedure for failed back surgery syndrome. Surgical technique and technology will fail when an inappropriate patient is selected for surgical intervention; failure also occurs particularly in lumbar disc protrusion if lateral recess stenosis is undiagnosed and untreated at the time of surgery. The patient's motivation status also has a significant effect on surgical outcome and the optimum patient to submit to surgery for failed back surgery syndrome has sciatica, more severe than backache, a recurrent or residual disc protrusion associated with the stenosis and excellent motivation which is not affected by workers' compensation or other insurance claims or benefit. PMID- 8215192 TI - Evaluation of intraoperative ultrasound in neurosurgery. AB - The value of real-time ultrasonography as a means of guidance during neurosurgical operations was assessed in a prospective study comprising 89 cases. There were 75 cranial and 14 spinal cases. After every such operation involving the ultrasonographic guidance, the operating surgeon subjectively assessed its usefulness vis-a-vis the information and/or help provided by it, on a scale ranging from 0 (no use) to 3 (invaluable). The intraoperative ultrasonographic guidance has been found to be extremely helpful in quickly and easily locating a small, deep-seated supratentorial lesion as also in certain spinal cases. In the absence of the much costlier CT/MRI-guidance system, intraoperative use of ultrasonography offers the desired help in majority of neurosurgical cases requiring intraoperative guidance. Additionally, it has got certain distinct advantages over the CT/MRI-guidance system. PMID- 8215193 TI - Huntington's disease in five siblings. AB - Huntington's disease is an autosomal dominant neurodegenerative condition which is rare in Singapore. Five siblings with progressive chorea and dementia were treated at the Singapore General Hospital and followed up over a seven-year period. Family history revealed five deceased affected individuals, two living affected siblings and more than 35 "at risk" offspring spanning another two generations each with about a 50% probability of carrying the Huntington's disease gene. We believe this is the largest kindred with Huntington's disease in Singapore. PMID- 8215194 TI - Computed tomography in patients with recurrent seizures. AB - Eighty patients had Computed Tomography (CT) performed for evaluation of epileptic seizures. Abnormal scans were found in 37 of the 80 patients (46.3%). Focal CT abnormalities were seen in 26 of the 80 patients (32.5%). Tumors were present in four and arteriovenous malformation (AVM) in three. Simple partial motor seizures were most strongly correlated with abnormal scans (five, 45.4%). Nineteen out of 21 patients with focal electro-encephalographic (EEG) abnormalities had focal CT abnormality compared to one out of 15 of those with generalised abnormality. 88.9% of patients with hemiplegia had abnormal scans. Whilst focal EEG abnormalities and abnormal neurologic signs pointed to a higher likelihood of CT abnormality, two subjects who were shown to have vascular malformations had normal EEG and neurologic exams. Routine CT scanning for evaluation of patients with recurrent seizures is advocated. PMID- 8215195 TI - Transcallosal approach to anterior and mid-third ventricular tumors--a review of 62 cases. AB - Sixty-two consecutive patients with anterior and mid-third ventricular lesions were operated on by a limited anterior transcallosal approach from 1987 to 1992. Fifty-six cases were operated on by B K M. Following lateral ventricular entry, transforaminal route to the third ventricle was preferred and utilised in 44 cases. An interfornicial or subchoroidal approach was employed only if transforminal entry was not adequate and was the route in 16 and two cases respectively. Enlargement of the foramen of Monro by incising its margins was not resorted to in any case. The age of the patients ranged from six to 64 years, (mean 29 years). Males were twice as often affected as females. There were 50 benign lesions: 43 colloid cysts, two craniopharyngiomas, one arachnoid cyst and four cysts of uncertain histology, and 12 malignant tumours: eight intrinsic astrocytomas, two oligodendrogliomas, one ependymoma and one primary lymphoma. The outcome in the benign cases was excellent in 42, good in six and poor in one. There was one post-operative death due to meningitis. PMID- 8215196 TI - Low energy laser therapy for treatment of post-herpetic neuralgia. AB - Post-herpetic neuralgia is a significant and severe disability that afflicts some patients following the acute manifestation of the disease despite what may be considered adequate pharmacological treatment at the time of onset of the vesicular rash. Surgery in general has little to offer in this condition although dorsal route entry zone lesions may be appropriate in some situations. Low dose laser therapy has been of value in a small series, to date, of cases that the treatment has been used on. This has been both in the early phase soon after the vesicles have cleared and often late, many years after the onset of the pain. Reported is a good improvement rate in approximately 60% of cases. The treatment is non-invasive and consideration of initial laser therapy is advocated. PMID- 8215197 TI - Study of Circle of Willis in 1021 consecutive autopsies: incidence of aneurysms, anatomical variations and atherosclerosis. AB - Incidence of subarachnoid haemorrhage from aneurysmal rupture is very low in India when compared with that in the Western world and Japan. Either they are not recognised or diagnosed adequately or there may be a true decreased geographical/racial incidence. To have an idea of the true incidence of aneurysms, a study of Circle of Willis with its anatomical variations and incidence of atherosclerosis was carried out in 1021 consecutive autopsies. The incidence of anatomical variations was slightly less than that seen in most of the other studies. Atherosclerosis was seen in 9.2% of the Circles of Willis. There were only two aneurysms, both located at the bifurcation of middle cerebral artery. This incidence of 0.2% is definitely much lower than that seen in other series, thus, suggesting that the incidence of subarachnoid haemorrhage from aneurysmal rupture is likely to be genuinely less in India. PMID- 8215198 TI - Stereotactic management of intrinsic brain stem lesions. AB - Between 1981 and 1991, seventy-two cases of brain stem lesions have undergone CT or MRI-directed stereotactic surgery using the Brown-Roberts-Wells or Cosman Roberts-Wells stereotactic systems. In 16 cases, the pre-operative diagnosis of haematoma had been made and the procedure was for therapeutic aspiration. In fifty-six cases, the pre-operative diagnosis was uncertain although intrinsic tumour was suspected. Histological diagnosis was obtained in fifty-four of these and unexpected findings of haematomas, granulomas, leucoencephalopathy, demyelinating disease, vasculitis and radiation necrosis occurred in over 15% of the cases. There were no operative deaths and morbidity was low. Advances in neuroradiological imaging with CT and MRI have increased the detection rate of brain stem lesions and image-directed stereotactic biopsy makes it possible in most cases to obtain histological diagnosis with relatively low morbidity which is important for treatment and prognosis. MRI-directed biopsies can compliment CT guided biopsies in most cases where the lesion is not adequately delineated on the CT image. PMID- 8215199 TI - Influence of basal cisterns, midline shift and pathology on outcome in head injury. AB - The relationship of outcome to the basal cisterns, midline shift and pathology as seen on initial CT scan was assessed in 107 moderate and severe head injured patients. The mortality rates were 82 cases (76%) and 29 cases (27%) among those with obliterated and normal basal cisterns, and 74 cases (69%) and 42 cases (39%) when the midline shift was present and absent, respectively. The state of the cisterns and midline shift was correlated with the type of intracranial pathology and Glasgow Coma Scale (GCS) scores. The state of the cisterns and midline shift was more important for those with single contusions and intra-cerebral haematoma (ICH) than for those with multiple lesions, extradural haematoma, subdural haematoma, diffuse cerebral oedema and normal CT scan. The state of the above two parameters when correlated with GCS score, showed that they were important for those with higher GCS scores. This indicates that the status of the cisterns and midline shift is correlated with the type of pathology and GCS score rather than these parameters taken alone in prediction. PMID- 8215200 TI - Diverse applications of continuous lumbar drainage of cerebrospinal fluid in neurosurgical patients. AB - From 1984 to 1991, continuous lumbar drainage (CLD) of cerebrospinal fluid (CSF) had been applied in 48 neurosurgical patients. Eleven of them had CSF accumulation and/or leakage at the operative sites and 37 of them suffered from CSF rhinorrhea. Successful treatment was achieved in 98% (47/48) of patients. There was neither death nor infection noted in this series. Complication was found in only one patient who developed acute subdural haematoma with pneumocephalus six days after CLD. After emergency craniotomy and evacuation of haematoma, the patient recovered without neurological deficit. The results suggest that CLD is a simple, safe and effective method in the treatment of CSF accumulation and/or leakage at the operative sites, as well as CSF rhinorrhea of various aetiologies. PMID- 8215201 TI - Minimally invasive brain surgery. AB - Minimally invasive brain surgery refers to technological advances refining surgical access that have enabled neurosurgeons to reduce the morbidity and improve the accuracy and quality of neurosurgical procedures. These advances include computer-assisted stereotaxis, intraoperative ultrasound, brain mapping and neuroendoscopy. Computer-assisted stereotaxis includes not only smaller and accurate craniotomies but precision radiotherapy with radiosurgery and interstitial brachytherapy. PMID- 8215202 TI - Current issues in neural transplantation. AB - Neural transplantation research has resulted in many important advances in neurobiology in the last hundred years. Neural transplantation for Parkinson's disease (PD) has developed since 1985, but the overall results of autogenous adrenal medulla transplantation have been disappointing. Graft survival is poor, benefits transient and morbidity high. Peripheral nerve is a rich source of nerve growth factor (NGF) and has been co-grafted with adrenal medulla in an attempt to improve these results. Foetal tissue grafting has shown more promise with sustained clinical improvements noted, and some evidence of graft survival noted on Positron emission tomography (PET) scans. The optimal technique is to use three to four foetuses from induced abortions of 6.5 to eight weeks gestation with multiple stereotaxic implants into the putamen and caudate nucleus. Most investigators recommend immunosuppression post-operatively. Host tissue recovery appears to be an important mechanism for this clinical improvement. Foetal neural grafting has also been performed for Huntington's disease, diabetes insipidus, and hereditary cerebellar ataxia. Although foetal forebrain cholinergic and spinal grafts have been performed in animals, these have not yet been attempted for Alzheimer's disease, or spinal cord damage respectively in humans. Neural transplantation as a therapy for human central nervous system disease is at an early stage of development, but holds much promise for the future. It should only be undertaken by multidisciplinary groups, using strict research protocols. PMID- 8215203 TI - Photodynamic therapy of brain tumours. AB - Photodynamic therapy is a binary treatment combining the selective uptake of a photosensitizer into a tumour followed by irradiation of the tumour with light of the appropriate wavelength to cause activation of the sensitizer as selective tumour kill. Photodynamic therapy has been extensively investigated in laboratory studies in the treatment of cerebral tumours and has been utilised in clinical trials to treat a variety of tumours including cerebral glioma. The clinical trials have usually used PDT as an adjuvant therapy following tumour resection but studies are being undertaken to use the treatment in combination with stereotactic techniques. The photosensitizer haematoporphyrin derivative (HpD) has been shown to be selectively localised into all grades of glioma with a direct correlation between the grade of glioma and HpD level in the tumour. The levels were highest in the glioblastoma multiforme (mean uptake of 5.9 micrograms HpD/g tumour wet weight) and lower in the intermediate grade anaplastic astrocytoma (2.4 micrograms/g) and low grade astrocytoma (1.6 micrograms/g). Uptake into normal brain tissue taken from HpD sensitized patients was 0.2 microgram/g. HpD was also localised into the brain adjacent to the tumour region. PMID- 8215204 TI - Surgery for stroke. AB - Studies on the natural history of cerebrovascular disease have shown that patients with symptomatic tightly stenosed and occlusive disease of the internal carotid artery are at high risk of subsequent stroke. However, carotid endarterectomy is still unpredictable in its outcome and morbidity and mortality levels do not support surgery in asymptomatic mild or moderate stenosis. The prime indications for surgery are transient ischaemic attacks (TIAs) and transient stroke with focal lesions of the origin of the internal carotid artery. Combined severe stroke morbidity and mortality should be less than 4%. Extra intracranial bypass is indicated when cerebral symptoms are associated with low cerebral perfusion. Symptomatic smooth tight stenoses of the origin of the aortic arch branches are effectively treated with angioplasty and occlusion of these origins with bypass surgery. More research is required into the prevention of atheroma, methods of reducing thrombo-embolism and means of undertaking safe surgery. With this must be linked the study and management of acute ischaemia and post-stroke rehabilitation. PMID- 8215205 TI - Epidemiology of epilepsy in Singapore. AB - Though epilepsy is recognised as a major medical and social problem in Singapore, there is no epidemiological survey to realise the size of the problem. We studied this problem from data collected from hospitals, school health clinics and from military statistics. The prevalence varied in the three sample populations studied. The most accurate data for prevalence study were obtained in army recruits. A life-time prevalence of 3.8 per 1000 was noted. The prevalence variation with age, sex and races is discussed. The mortality from epilepsy was 0.5 per 100,000. The types of epilepsies and the treatment patterns are discussed. PMID- 8215206 TI - Neuro-radiology of skeletal fluorosis. AB - Though fluorosis is prevalent in certain geographic parts of the world, it is likely to occur in other parts due to industrial intoxication and also in people with latent kidney disease even when they consume relatively lower amounts of fluoride than in endemic regions. A sizeable number of patients suffering from ossified posterior longitudinal ligament (OPLL) may have fluoride intoxication as the underlying cause. The clinical, radiologic and pathologic manifestations of OPLL in non-orientals have been reported to be very similar to those in orientals. The question whether all these entities reported from different ecospheres of the globe have common aetiological factors is worthy of further research. Though plain radiology shows the characteristics of fluorosis, CT and MR imaging modalities are very helpful in early diagnosis and also in planning proper surgical intervention. PMID- 8215207 TI - Epilepsy surgery in children and adults. AB - Epilepsy surgery is now accepted as a treatment modality for medically intractable epilepsy. A careful and detailed evaluation of patients is required by a trained epilepsy team which includes neurosurgeons, neurologists, neuroradiologists, psychologists and psychiatrists. For intractable complex partial seizures of temporal lobe origin, epilepsy surgery offers an 80% success rate. PMID- 8215208 TI - Intraoperative sonography in neurosurgery. AB - Intraoperative sonography is not employed as often as it should be. This report describes the techniques of intraoperative sonography during craniotomy. The authors have performed this in 15 cases. Details of three cases wherein the lesion was localised easily at operation are given. Surgical excision can be done after this procedure without producing any major deficit. PMID- 8215209 TI - Acute necrotising myopathy in association with carcinoma of the tongue. AB - Acute necrotising myopathy (ANM) is a rare complication of carcinoma. The myopathy is proximal, rapidly progressive, associated with rhabdomyolysis and usually fatal. We report an unusual case of acute necrotising myopathy in a woman with squamous cell carcinoma of the tongue who is alive, without tumour recurrence two years after diagnosis. This association of ANM with head and neck cancer is unique. PMID- 8215210 TI - A proposed pathogenetic process in the formation of Aspergillus mycotic aneurysm in the central nervous system. AB - By selectively infiltrating and destroying the internal elastica of a major cerebral artery, Aspergillus fungus (Af) induces disruption and incipient dilatation of the vascular wall with or without inflammation. This unique pathogenetic mechanism of forming "true" fungal mycotic aneurysms (FMAs) was clearly demonstrated in a middle-aged adult male who died of a pontine stroke. The latter was secondary to thrombosis in the basilar artery of which the internal elastica was infiltrated and replaced by Af hyphae. The patient had diabetes, liver cirrhosis with oesophageal varices, and received multiple blood transfusions. However, leukopenia was not present and immunosuppressive drugs were not used. This case prompted comparison of the natural history and pathogenesis of bacterial and fungal mycotic aneurysms in cerebral arterial branches. Selective destruction of the internal elastica with progressive dilation at a segment of vascular wall insinuates a potential pathogenetic process involved in the formation of saccular or berry aneurysm. Management and therapeutic approaches for FMA are discussed. PMID- 8215211 TI - Recovery from aphasia and conversion of handedness: a case report. AB - A remarkably rapid and complete recovery from aphasia and conversion from right to left handedness was documented in a hemiplegic individual after surgery for an arteriovenous malformation (AVM) in the dominant hemisphere. The possible mechanisms of recovery were discussed and we have reviewed the literature about the pattern of cerebral dominance. Her rapid recovery could be explained by the co-dominance of the right and left cerebral hemispheres. PMID- 8215212 TI - Unusual non-osseous compression at the craniovertebral junction--a report of four cases. AB - A variety of congenital and acquired non-osseous compression elements at the craniovertebral junction have been known and a fibrous band among them is unusual. Unaccompanied by any bony abnormality, non-osseous compression due to thickened epidural tissue, possibly congenital, presenting in adulthood is described in four cases. The onset of symptoms was in the fourth and sixth decades. Three were males and one was a female. The clinical picture was a slowly progressive spastic quadriparesis except in the only female patient who developed sudden quadriplegia while carrying a weight over her head. MR tomography was diagnostic while CT scan ruled out any bony pathology. Release of the localised epidural constriction was performed in all; in one transorally. Good recovery ensued postoperatively while histopathology excluded infective or neoplastic pathology. PMID- 8215213 TI - Bilateral proptosis after post-traumatic hydrocephalus: a case report. AB - Hydrocephalus can cause several neuro-ophthalmological complications but only rarely has it been reported to cause proptosis. A 23-year-old woman developed post-traumatic hydrocephalus after a road traffic accident. She was found to have deteriorating visual acuity bilaterally and bilateral proptosis. Both these complications resolved after a ventriculo-peritoneal shunt was inserted. PMID- 8215214 TI - Morphology and nuclear contents in IVF embryos. AB - Human pre-embryos, at 2-8 cells, with different morphology have been examined for chromosome constitution. Concerning the informative pre-embryos (23/65), 11 showed a normal karyotype and in 12 an abnormal karyotype was observed; there was not a complete correspondence between pronucleation and chromosome set. Also in the interphasic pre-embryos the presence of chromatin masses at different sizes was revealed. The observation of polyploid and/or polynucleated blastomeres can suggest a failure of synchronization between cytoplasmatic and nuclear division. Mosaicism, polyploidy and polynucleation are phenomena that could be caused by in vitro culture conditions or dependent upon the genetic anomaly of the zygote. PMID- 8215215 TI - Cytogenetic findings in echographically defined blighted ovum abortions. AB - A sample of 52 spontaneous blighted ovum abortions (BO) was examined cytogenetically and compared with a sample of abortions with echographic evidence of the embryo (AE). Abnormal karyotypes were 67% in the BO sample and 53% in the AE sample, a non significant difference. In the BO abortions trisomies were 74% of the abnormal karyotypes but 35% in the AE abortion, and the 45,X karyotype was absent among the BO but was found in 10 cases of AE. The prevalence of trisomies 16 and 22 in the BO abortions indicates that genes on these chromosome may be responsible for the early arrest of embryonic development. PMID- 8215216 TI - A genetic study of otosclerosis in a population living in the north of Tunisia. AB - The frequency of otosclerosis has been estimated to be 0.6 per 100 inhabitants in a population living in the North of Tunisia. The sex ratio in probands is 0.73 with clinical otosclerosis being approximately twice as frequent in females than in males, an observation which could be due to hormonal factors. The main risk period for otosclerosis is between 25 and 35 years of age in both sexes. Segregation analysis was performed in 193 nuclear families belonging to 65 pedigrees of otosclerosis. The pattern of the disease is due to a rare dominant major gene with a high polygenic component. This finding was unexpected since otosclerosis is usually considered to be a disease with simple dominant inheritance and incomplete penetrance. The authors have estimated that only 13% of affected patients are carriers of the rare dominant gene. This gene has strong penetrance which, however, varies according to age and sex. PMID- 8215217 TI - An unusual Gazella dama karyotype. AB - The chromosomes of a female gazelle (Gazella dama) were investigated using GTG, RBG and C banding techniques. Their banding patterns showed that autosomes are involved in a complex of four Robertsonian translocations. PMID- 8215218 TI - Identification of ring Y chromosome: cytogenetic analysis, Southern blot and fluorescent in situ hybridization. AB - A young male with a 45, X/46, X, r(Y)/47, X, r(Y), r(Y)/48, X, r(Y), r(Y), r(Y) karyotype was described. The phenotype was substantially characterized by short stature (< 3rd centile) and by a scrotal hypospadias with a normal sized penis. Fluorescent in situ hybridization (FISH) and molecular analysis by X and Y chromosomes specific probes were performed to identify the origin of the marker chromosomes which had been impossible to define by conventional and high resolution cytogenetics techniques. Small rings was identified as Y-derived ring chromosomes, lacking the entire heterochromatic portion of the long arm and the very distal tip of the short arm. The correlation between the phenotype and the chromosome constitution of the propositus was discussed. PMID- 8215219 TI - A distinct multiple congenital anomalies syndrome associated with distal 5q deletion (q35.1qter). AB - In this report the authors describe a multimalformed female newborn with terminal deletion of the long arm of chromosome 5 (q35.1qter). The multiple congenital anomaly syndrome consisted of a combination of oral, facial and digital anomalies. The present observation indicates that cytogenetic studies are needed in all patients presenting developmental delay and oro-facio-digital anomalies not consistent with the diagnosis of oro-facio-digital syndromes type I and type II. PMID- 8215220 TI - A specific phenotype associated with trisomy 15 mosaicism. AB - In this report the authors describe the phenotype of a female newborn with trisomy 15 mosaicism and double aneuploidy (47, XX, +15/47, XXX). Comparison with the two other patients with trisomy 15 mosaicism reported up to now, reveals a distinct phenotype with typical craniofacial dysmorphism, severe hypotonia and general symptoms and signs compatible with a fetal akinesia sequence. PMID- 8215221 TI - Evidence of chromosomal fragile sites in schizophrenic patients. AB - Chromosomal fragility and other chromosomal abnormalities were frequently observed in subjects with neuropsychiatric disorders, such as fragile X syndrome, autism or schizophrenia, but only for the first one the fragility is accepted to be associated to a specific pathology, so that it is used as a diagnostic marker. In this study the authors analyzed 50 schizophrenic males, searching for the rare fragile sites or other aberrations with the method suitable for fra(X) detection. Chromosomes from schizophrenic patients resulted more fragile than those from normal controls, especially chromosome 9. The authors discuss the implications of a possible association of these data with the aetiopathogenesis of schizophrenic syndrome. PMID- 8215222 TI - Acrocallosal syndrome and 12p. PMID- 8215223 TI - [Brain morphometry using MRI in Cri-du-Chat Syndrome. Report of seven cases with review of the literature]. AB - The authors present the results of a morphometric study of the brain of 7 patients with cat cry syndrome, explored with Magnetic Resonance Imaging (MRI). A method is proposed in order to facilitate the identification of the anatomical slices. A characteristic anomaly is observed as a marked atrophy of the brainstem predominating at the pontine level and associated with a small cerebellum, atrophic middle cerebellar peduncles and cerebellar white matter. This apparently systematized atrophy obvious in children, seems similar to the one observed in patients presenting a olivopontocerebellar atrophy, possibly correlating with disturbance of coordination and developmental delay in motility as observed in these patients. This does not implicate the same subjacent functional neuroanatomical pathways. PMID- 8215224 TI - Karyotypes of single blastomeres isolated from abnormal preimplantation human embryos. AB - Two hundred and thirty three-isolated blastomeres originating from 82 abnormal human 2 to 11-cell embryos were fixed separately for cytologic and cytogenetic analyses. These embryos were rejected from our in vitro fertilization program because of either the presence of 1 or 3 pronuclei when observed 17 hours after insemination, or a wide fragmentation of normally fertilized eggs, or delayed fertilization. Twelve per cent of the blastomeres had no nuclei, whereas 7% were binucleated. When comparing the different types of embryos, parthenogenetic ones were those displaying the closest to normal development, since only 3% were cytologically abnormal. Seventy-six percent of the embryos had at least one analysable mitosis. Only 33% had 2 analysable mitoses, and 11% at least 3. Embryos with more than 1 analysable mitosis were the most often mosaicisms. When compared with classical techniques involving the fixation of whole embryos, cytogenetic analysis of isolated blastomeres permits ensuring that the number of chromosomes per cell is not overestimated as a consequence of mixed mitoses and demonstrates the very high incidence of mosaicism in abnormal human embryos. PMID- 8215225 TI - [Cytogenetic study of fragmented embryos not transferred in in vitro fertilization]. AB - A cytogenetic analysis was performed on a sample of 411 human grade IV embryos (i.e. poor morphological quality embryos, never transferred in our in vitro fertilization (IVF) pro Gram) in order to investigate the chromosomal status of these embryos. One hundred eighteen were successfully karyotyped from at least one metaphase. Only 10% displayed normal diploid metaphases. Aneuploidy was the most frequently observed abnormality, with a rate of 36.4%. Six cases of single chromatids were noted and 9 embryos showed structural aberrations. Polyploidy (from 3n to 7n) and haploidy were also observed, suggesting parthenogenetic activation, polyspermy or chromosomal duplication. Mosaicism constituted 6% of the abnormalities. Thirty embryos exhibited fragmented chromosome sets which might result from in vitro delayed fertilization. PMID- 8215226 TI - Genetic polymorphisms in the white population of Victoria, Australia. AB - Genetic variation in the rural population of the State of Victoria, Australia, is demonstrated through the analysis of eight genetically independent red cell antigen, red cell enzyme and plasma protein systems in a sample of more than 2000 blood donors. The polymorphisms investigated were ABO, RH, KEL, esterase D (ESD), glyoxalase 1 (GLO1), phosphoglucomutase locus 1 (PGM1), haptoglobin (HP) and the third component of complement (C3). For genetic distance analysis the sample was subdivided into nine regions using the Victorian Government's Statistical Divisions. Considerable regional genetic heterogeneity exists; with the Goulburn and the Central Highlands divisions being the most distinct, not only from the other seven divisions, but also from each other. The pattern of micro differentiation is complex and cannot be easily explained, but there is evidence of varying levels of systematic evolutionary pressure on the Victorian divisions. The investigation of the proportion born overseas in each division, and their respective countries of origin, did not help in the interpretation of the findings. Overall, rural Victorians exhibited allele frequencies very similar to the populations of both Melbourne, the Victorian capital, and the island State of Tasmania. PMID- 8215227 TI - Relation between serum uric acid and blood pressure in adolescents. AB - In adults, serum uric acid is positively associated with blood pressure levels. It is also a predictor of the development of hypertension in normotensive adults. The purpose of this study was to examine the relation of serum uric acid to systolic and diastolic blood pressure in adolescents. The data, from Cycle III of the National Health Examination Survey, consisted of a national probability sample of 6768 youths, 12-17 years old, in the United States. With age, height, weight, and sexual maturity controlled, serum uric acid significantly predicted blood pressure in adolescents. This relationship of uric acid and blood pressure was evident in male, but not female, adolescents. In association with findings from adult studies, these results indicate that uric acid levels may be useful indicators of adolescents at risk for hypertension. PMID- 8215228 TI - Inertial characteristics of children and their application to growth study. AB - The water displacement method was used in this study to obtain volume distribution data on limb segments. A mathematical method was then applied to those data to calculate the values for centre of gravity, radius of gyration, principal moment of inertia, and volume. The results showed the water displacement method is not sensitive to random error, while giving a good estimation of inertial properties. Centre of gravity, expressed as percentage of segment length, has a very small variance; the variance of radius of gyration was even smaller. These two variables show sex-related differences, the former also displaying differences relating to age, especially for multi-segment units such as the forearm with hand. The principal moment of inertia and volume were highly correlated with anthropometric variables. Volume ratios had significant sex and age differences, absent for the absolute value for volumes. Since the results demonstrated characteristics absent from conventional anthropometric investigation, the inertial properties may find an application as new indicators of children's growth. It has also noted that the results from previous studies had different results for some inertial characteristics, indicating a need for further studies of the inertial properties of the human body. PMID- 8215229 TI - Phenotypic and genetic affinities among ethnic populations in Daghestan (Caucasus, Russia): a comparison of polymorphic, physical, neurophysiological and psychological traits. AB - Daghestan contains many distinct populations characterized by different degrees of isolation, ethnic backgrounds and ecological conditions. This report introduces a large-scale family study conducted in seven Daghestan populations as well as in Moscow, using four categories of measures: (1) single gene polymorphisms, (2) anthropometric, (3) physiological, and (4) psychological quantitative traits. Such a study permits the analysis of both phenotypic and genetic variation within and between populations. The implications of such variation are discussed, especially in the context of the measures used. These derive from Soviet conceptualizations of the nervous system and related assessment of individual differences, and vary considerably from conventional Western approaches to behaviour. From the anthropometric through the physiological to the behavioural measures there was a clear trend towards increased phenotypic variation but reduced genetic variation. Possibly because the genetic variance was less on the more complex phenotypes, measures of generalized distance indicated much greater population similarity when based on phenotypic data on the genetic component of variation. Issues that arise when using behavioural traits to study human population diversity are discussed, particularly in relation to inbreeding and the specific cultural and linguistic practices in the Daghestan region. PMID- 8215230 TI - The association between height and some structural social variables: a study of 10-year-old children in Stockholm during 40 years. AB - The associations between height of 10-year old children and mother's age, family size, number of inhabitants per room and father's occupational level were investigated over a period of 40 years. The analyses were based on samples of 10 year-old Stockholm schoolchildren born in 1933, 1943, 1953 and 1963. Family size consistently associated with height. Father's occupational level showed a statistically significant association only for children growing up in the 1930s and 1940s, and the number of inhabitants per room only during the 1930s. Mother's age was significantly associated with height only in the cohort of children born in 1963, taller children having older mothers. The influence of the structural social factors taken together on height variation was lowest in the 1953 cohort; its magnitude in the 1963 cohort was the same as in the 1943 cohort. PMID- 8215231 TI - A new method for accurate dental measurement. AB - Using digital dividers (analogue-digital transformer, Brandt-Hermanussen device), it has become possible to measure distances between human teeth with a technical error of 0.04 mm. The technique implies a small preparation (trough) into the respective teeth. The ball-shaped metal probes of the instrument fit into these troughs and enable the determination of this distance directly in the patient. It does not require the use of casts. The present method was compared with two conventional and popular techniques of tooth arch determination, using the natural retentions of the deepest points of the central fossa of the respective teeth without the preparation of an artificial trough (manual caliper rule with nonius, digital caliper rule). The technical error of these techniques ranged between 0.46 mm and 0.52 mm. In order to investigate whether the preparation of an artificial trough could be avoided, the digital measuring dividers were modified and equipped with sharp probes for the determination of the natural distance between the deepest points of the central fossa, in analogy to the conventional techniques. Under these circumstances however, the technical error increased up to 0.27 mm (observer 1), and 0.21 mm (observer 2). It is concluded that dental marking is necessary for accurate dental measurement. PMID- 8215232 TI - Co-evolution of glucose-6-phosphate dehydrogenase deficiency and quinine taste sensitivity. AB - We hypothesized that 'quinine' taste sensitivity functions to regulate the intake of bitter-tasting, naturally occurring antimalarial substances of plant origin, and that this genetic trait has co-evolved with the G6PD locus. This hypothesis was tested by evaluating taste sensitivity to quinine sulphate and sodium chloride among 17 G6PD-deficient and 25 G6PD-normal African American subjects 14 40 years of age. There was no significant difference in mean 'quinine' taste sensitivity between the two groups, although there was a trend towards greater 'quinine' taste acuity among the G6PD-deficient subjects. A larger study sample would provide a fairer test of the hypothesis. PMID- 8215233 TI - A prevalence and fertility study of haemochromatosis in Saguenay-Lac-Saint-Jean. AB - The prevalence of hereditary haemochromatosis (HH) in Saguenay-Lac-St-Jean (SLSJ), a geographically isolated region of northeastern Quebec, was estimated at 0.014; the heterozygote frequency was 0.21. These are among the highest frequencies found thus far in white populations. The fertility study completed in SLSJ showed that carriers of the HH gene tended to have more children than non carriers. However, since these differences were not statistically significant, there appears to be no basis on which to accept that HH heterozygotes are at a selective advantage. Therefore, genetic drift cannot be excluded. PMID- 8215234 TI - High-density lipoprotein cholesterol concentrations and postheparin hepatic and lipoprotein lipases in obesity: relationships with plasma insulin levels. AB - The concentration of high-density lipoprotein (HDL) cholesterol in patients with severe obesity is generally subnormal. The exact mechanism linking obesity with reduced levels of HDL cholesterol remains unclear. In this study we evaluated the postheparin plasma lipolytic enzymes lipoprotein lipoprotein lipase (LPL) and hepatic lipase (HL) in a group of 24 obese women compared with controls and analyzed the interrelationships between insulin, postheparin lipolytic enzymes and HDL subfractions. Total HDL cholesterol was significantly lower in the obese subjects than in the controls, and the difference was mainly due to HDL2 cholesterol concentrations. Mean fasting glucose, insulin and the summated means of glucose (sigma glucose) after the oral glucose tolerance test (OGTT) were not significantly different in the two groups. The summated means of insulin (sigma IRI) after the OGTT were significantly higher in the obese women than in the controls. LPL, HL and the HL-to-LPL ratio were significantly higher in the obese women than in the controls. HL and LPL correlated positively with sigma glucose, sigma IRI and body mass index (BMI) and negatively with plasma triglycerides. Partial correlation analysis demonstrated that, when exposed to similar sigma IRI values, HL and LPL were no longer correlated with sigma glucose, plasma triglycerides and BMI. HDL2 cholesterol levels were negatively correlated with HL, posthepatic plasma lipolytic activity, sigma glucose, plasma triglycerides and BMI. HDL2 cholesterol concentrations were directly correlated with LPL. Partial correlation analysis showed that when exposed to similar HL and LPL values, HDL2 cholesterol values were no longer correlated with sigma glucose, sigma IRI, plasma triglycerides and BMI. Therefore, our results demonstrate that the low HDL2 cholesterol levels found in obese women may be related to the high levels of HL and to the high HL-to-LPL ratio which in turn could be determined by the peripheral insulin resistance. PMID- 8215235 TI - Dietary diacylglycerol-dependent reduction in serum triacylglycerol concentration in rats. AB - The effects of dietary diacylglycerol consisting of 1,3 (65.2%) and 1,2 species (32.6%) and triacylglycerol (rapeseed oil) on the serum and hepatic lipid profiles were compared in the rat. The fatty acid composition was similar between these dietary lipids. The dietary acylglycerols were added to the experimental diets so as to provide the same amounts of fatty acids (9.39%). Dietary diacylglycerol compared with triacylglycerol significantly reduced concentrations of serum triacylglycerol at 17 and 34 days of the feeding periods without influencing those of phospholipid and cholesterol. There were no significant differences in the concentrations of hepatic triacylglycerol, cholesterol and phospholipid between the two groups of rats at 34 days of the feeding period. In the second trial, triacylglycerol in the experimental diet was replaced by varying amounts of diacylglycerol while maintaining the fatty acid contents (9.39%). After 14 days of the feeding period, significant reductions in serum triacylglycerol levels were confirmed in the groups of rats fed the diets in which diacylglycerol fatty acids supplied more than 50% (50, 75 and 100%) of total dietary fatty acids. Thus, it was confirmed that dietary diacylglycerol compared with triacylglycerol exerts a potent serum triacylglycerol-lowering effect in the rat. PMID- 8215236 TI - Hepatic de novo fatty acid synthesis in the rat. AB - Generally, the rate of hepatic de novo fatty acid (FA) synthesis (lipogenesis) in vivo is determined by measuring the amount of newly synthesized FA present in the liver 1 h or less after injection of label (3H2O) for FA synthesis (1-hour value of labelled FA). Since this value may well be affected by momentary conditions, our objective was to investigate whether the amount of labelled FA present in the liver 24 h after injection of 3H2O can be used as a parameter of lipogenesis (24 hour value of labelled FA). To this end, effects of the amounts of dietary fat, sucrose and linoleic acid and the effect of meal feeding versus d libitum feeding on this 24-hour value were investigated. The 24-hour value decreased with the dietary fat level and was higher in rats fed a diet in which starch was partly replaced by sucrose [20% of metabolizable energy (E%)]. This is in accordance with literature data on the 1-hour value of labelled FA. No effect of meal feeding versus ad libitum feeding on the 24-hour value of labelled FA was found. Furthermore, no significant effect of the dietary linoleic acid level (1-10 E%) on the 24-hour value of labelled FA was found, although when lipogenesis was stimulated by feeding a diet containing 20 E% sucrose, the 24-hour value tended to be higher at 1 E% linoleic acid than at 2.5 E% linoleic acid or higher. PMID- 8215237 TI - Importance of exogenous cholesterol in diabetic rats: effects of treatment with insulin or with an acyl-CoA:cholesterol acyltransferase inhibitor. AB - Contrary to normal rats, diabetic rats fed a cholesterol-rich diet become markedly hyperlipidemic. We have previously reported [J Lipid Res 1992; 33:1475 14841bd that the intestinal acyl-CoA:cholesterol acyltransferase (ACAT) plays a major role in the initiation of diabetes-associated hypercholesterolemia. In the present study, we have shown that within the 3 days following diabetes induction by streptozotocin, diabetic rats responded to dietary cholesterol in a dose dependent manner and their livers developed a large capacity to store cholesteryl esters (up to 10.6 +/- 1.4 mg/g tissue). We also examined the effects of treatments with insulin or with the ACAT inhibitor CL-277082 on the uptake of exogenous [3H]-cholesterol in 3-day diabetic rats. The amount of [3H]-cholesterol in chylomicrons was dramatically increased by the diabetic state (+110%; p < 0.01) reflecting a higher rate of cholesterol absorption compared to normal rats. This change was dependent on the ACAT activity since the CL-277082 treatment largely prevented the appearance of [3H]-cholesterol in chylomicrons (-88%; p < 0.001), and as a consequence in the other lipoprotein classes. Insulin treatment reduced only by 35% (p < 0.05) the [3H]-cholesterol in chylomicrons compared to the diabetic control rats, and failed to normalize the resulting lipoprotein profile. These results indicate that as early as 3 days after diabetes induction, diabetic rats are highly sensitive to dietary cholesterol concentrations, and that insulin deficiency is not the sole factor involved in the cholesterol hyperabsorption, which was totally suppressed by the ACAT inhibitor treatment. PMID- 8215238 TI - Evolution of Mg deficiency in rats. AB - We performed weekly analyses of the evolution of the bioavailability of the Mg cation over a period of 70 days in adult rats fed an Mg-deficient (0.02%) diet. The results generally showed an increase in digestive utilization (% absorption) and a decrease in Mg balance during the experimental period. The parameters most sensitive to Mg deficiency were increase in body weight and blood concentration of Mg (mg/100 ml), which had declined significantly after 7 days (p < 0.05). Significant declines in plasma (p < 0.02) and muscle Mg (p < 0.01) were not apparent until after 35 days. Magnesium content in bone decreased from day 49 onward (p < 0.05), whereas renal Mg concentration tended to rise slightly during the last 2 weeks of study. No change was found in brain Mg concentration. PMID- 8215239 TI - Protective effects of sesamin against liver damage caused by alcohol or carbon tetrachloride in rodents. AB - The effects of sesamin, a potent inhibitor of delta 5-desaturase in polyunsaturated fatty acid biosynthesis, on the fatty acid compositions of tissue lipids and liver functions were examined in rodents. When a mixture of sesamin and episesamin (51.1:48.2, w/w) was given to rats at a dietary level of 0.5% for 13 days, the proportions of dihomo-gamma-linolenic acid significantly increased not only in the liver but also in plasma and hemocytes, suggesting an interference with delta 5-desaturation by these lignans. The sesamin preparation at the dietary level of 1% improved changes in various blood parameters of the mouse, such as aspartate aminotransferase and alanine aminotransferase activities, and the concentrations of total cholesterol, triglyceride and total bilirubin, caused by continuous inhalation of ethanol. In addition, sesamin showed a significant protective effect against the accumulation of fat droplets and vacuolar degeneration in the mouse liver, as confirmed on histological examination. Sesamin, at the level of 100 mg/kg body weight, also tended to prevent liver lipid accumulation by carbon tetrachloride in mice. These results indicate that sesamin and a related lignan compound have an ability to improve liver function. PMID- 8215240 TI - Sensory modulation and the spinal cord. PMID- 8215241 TI - Diffuse noxious inhibitory controls in humans: a neurophysiological investigation of a patient with a form of Brown-Sequard syndrome. AB - In normal subjects, the application of heterotopic painful stimuli induces simultaneous and parallel decrease in the sensation of pain and of the spinal nociceptive flexion (RIII) reflex evoked by electrical stimulation of the sural nerve. This inhibition of the RIII reflex is absent in tetraplegic patient with clinically complete spinal cord transections and can be triggered only from the analgesic hand in patients with Wallenberg's syndrome. These findings suggest that the inhibitory phenomena observed in normal subjects are likely to be examples of diffuse noxious inhibitory controls (DNICs), being sustained by a loop involving supraspinal structures, the ascending part of which is localized in the spinoreticular tract. We now report an exceptional case of a patient with Brown-Sequard syndrome due to a 4-year-old spinal cord lesion (left side, T-6 level) produced by a knife-wound in the back. Nociceptive flexion (RIII) reflexes elicited by stimulation of cutaneous afferents in the ulnar and sural nerves were studied in the upper and lower limbs by recording from the biceps brachialis and biceps femoris muscles, respectively. For each limb, the RIII reflex threshold was determined. The reflex was then elicited regularly by stimuli of 1.2 times threshold before, during, and after periods of nociceptive electrical conditioning stimulation (15 mA; 4 Hz; 1 min) applied successively to the other three limbs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215242 TI - The polymerase chain reaction in the diagnosis of Lyme neuroborreliosis. AB - The polymerase chain reaction is sensitive and specific in the detection of defined DNA sequences and holds promise for diagnosing the presence of fastidious microorganisms in human infectious diseases. We developed a methodology for nested polymerase chain reaction and hybridization analysis of the cerebrospinal fluid using primers from a genomic Borrelia burgdorferi sequence and applied it to the cerebrospinal fluid (CSF) of patients suspected of having Lyme neuroborreliosis and other diseases. Polymerase chain reaction and hybridization demonstrated extremely high sensitivity for spirochetal DNA, and was highly specific, with a false-positivity rate of less than 3%. However, the results were negative or indeterminate in 54% of CSF samples from patients with definite or probable disease, indicating an absence, or extremely low level, of spirochetes or spirochetal DNA in a significant percentage of patients with Lyme neuroborreliosis. Polymerase chain reaction and hybridization of the CSF can thus be considered a useful adjunct in diagnosis, but its negativity does not rule out Lyme neuroborreliosis. PMID- 8215243 TI - Cytochrome c oxidase reaction improves histopathological assessment of zidovudine myopathy. AB - Zidovudine can induce a mitochondrial myopathy with ragged-red fibers and partial cytochrome c oxidase deficiency. In an attempt to improve histological assessment of zidovudine myopathy, we evaluated cytochrome c oxidase histochemical reaction in the muscle of 10 patients with biopsy-proven zidovudine myopathy (Group 1), 10 myopathic zidovudine receivers without typical histopathological features of zidovudine myopathy (Group 2), and 10 human immunodeficiency virus (HIV)-infected patients not treated by zidovudine who had an immunohistological profile of HIV associated myopathy or other neuromuscular disorders (Group 3). Among zidovudine receivers, cytochrome c oxidase deficiency was found in 10 of 10 patients from Group 1 and 7 of 10 from Group 2. No cytochrome c oxidase deficiency was observed in patients not treated by zidovudine. When present, cytochrome c oxidase negative fibers accounted for 2 to 28% of fibers, and there was no difference for the number of cytochrome c oxidase-negative fibers between Group 1 and Group 2. Most patients with cytochrome c oxidase deficiency that could be evaluated clinically after muscle biopsy improved after withdrawal of zidovudine (5 of 7 in Group 1, 5 of 5 in Group 2). Patients who did not improve had an HIV-associated myopathy concurrently with zidovudine myopathy. We conclude that cytochrome c oxidase reaction may be used as a reliable marker of zidovudine mitochondrial toxicity in HIV-infected patients with muscular symptoms. PMID- 8215244 TI - Pathological markers associated with normal aging and dementia in the elderly. AB - We investigated the associations of pathological markers of Alzheimer's disease (AD) and diffuse Lewy body disease as well as possible markers of vascular dementia with cognitive function in a sample of 20 nondemented and 35 demented subjects (median age of both groups, 88 years) who had been studied prospectively for 4.0 +/- 2.1 years. Very old demented subjects almost always had nonneuritic senile plaques, but over half had no neuritic senile plaques and little other AD pathology. Five subjects had cortical Lewy bodies; all were demented. We propose that hippocampal sclerosis, leukoencephalopathy, and multiple lacunae are possible markers of vascular dementia. When grouped together, these markers were significantly associated with dementia and occurred in 40% of demented subjects. As the relative frequency of neuritic markers of AD (and possibly AD itself) declines in the tenth decade, vascular dementia may become an increasingly important type of dementia. PMID- 8215245 TI - Impairment of retinal increment thresholds in Huntington's disease. AB - We have investigated detection thresholds for a foveal blue test light using a Maxwellian view system in 61 normal subjects, 19 patients with Huntington's chorea, 14 patients with Tourette's syndrome, and 20 patients with schizophrenia. Ten measurements were made: The blue test light (1 degree diameter, 500 msec duration) was presented either superimposed on a yellow adaptation field (5 degree diameter) or 500 msec after switching off this field (transient tritanopia effect). In both cases five different background intensities were presented. The only abnormality found was in patients with Huntington's chorea. During adaptation these patients' thresholds are significantly higher than normal (p < 0.005). No change was found in the transient tritanopia effect. Huntington's disease causes degeneration of several different transmitter systems in the brain. Increment threshold testing allows for noninvasive investigation of patients and confirms the involvement of the retina in the degenerative process in Huntington's chorea. PMID- 8215246 TI - Side of onset of motor symptoms influences cognition in Parkinson's disease. AB - Studies attempting to relate cognitive impairment to asymmetry of motor symptoms in Parkinson's disease (PD) have found contradictory results. We examined 88 patients with unilateral onset of idiopathic PD who underwent a comprehensive neuropsychological assessment, including language, visuospatial abilities, abstraction and reasoning, attention and mental tracking, set shifting, and memory. Patients whose motor signs began on the left side of the body consistently performed more poorly on the battery of cognitive measures than did patients with right-side onset. Significant differences were found on immediate and delayed verbal recall, word retrieval, semantic verbal fluency, visuospatial analysis, abstract reasoning, attention span, and mental tracking. These differences could not be attributed to differences in the overall severity of motor symptoms at the time of cognitive assessment, or the current pattern of motor asymmetry. This finding suggests that damage to right-hemisphere dopamine systems plays a disproportionately greater role in PD-related cognitive decline than a presumably comparable left-hemisphere dopamine depletion. PMID- 8215247 TI - Procedural learning in Parkinson's disease and cerebellar degeneration. AB - We compared procedural learning, translation of procedural knowledge into declarative knowledge, and use of declarative knowledge in age-matched normal volunteers (n = 30), patients with Parkinson's disease (n = 20), and patients with cerebellar degeneration (n = 15) by using a serial reaction time task. Patients with Parkinson's disease achieved procedural knowledge and used declarative knowledge of the task to improve performance, but they required a larger number of repetitions of the task to translate procedural knowledge into declarative knowledge. Patients with cerebellar degeneration did not show performance improvement due to procedural learning, failed to achieve declarative knowledge, and showed limited use of declarative knowledge of the task to improve their performance. Both basal ganglia and cerebellum are involved in procedural learning, but their roles are different. The normal influence of the basal ganglia on the prefrontal cortex may be required for timely access of information to and from the working memory buffer, while the cerebellum may index and order events in the time domain and be therefore essential for any cognitive functions involving sequences. PMID- 8215248 TI - The transport of L-6-fluorodopa and its metabolites from blood to cerebrospinal fluid and brain. AB - The transport of L-6-fluorodopa and its major metabolites from the blood to the brain, cerebrospinal fluid (CSF), and muscle was studied in carbidopa-pretreated cynomolgus monkeys. A bolus intravenous injection of 18F-L-6-fluorodopa was followed by serial positron emission tomography scans and sampling of cisternal CSF and arterial blood. The relative concentrations of L-6-fluorodopa and its metabolites were determined in blood plasma and CSF by high-performance liquid chromatography. Raising the blood concentration of phenylalanine by intraperitoneal injection markedly reduced the accumulation of tracer in the brain. This indicates that L-6-fluorodopa and 3-O-methylfluorodopa, like native L dopa and its O-methylated derivative, are transported at the brain capillary by the large neutral amino acid carrier-mediated system, which is subject to saturation and competition by other large neutral amino acids (such as phenylalanine) at physiological plasma concentrations. In contrast, administration of phenylalanine had no effect on the accumulation of tracer either in muscle, or as L-6-fluorodopa and 3-O-methylfluorodopa, in CSF. This suggests that the transport of L-dopa and its derivatives at the blood-CSF barrier differs from the transport at the blood-brain barrier and also that measurement of CSF L-dopa is not a good index of the transport and pharmacokinetics of L-dopa in the brain. However, the effect of phenylalanine administration in reducing the concentration of fluorohomovanillic acid in the CSF suggests that the concentration of homovanillic acid in the CSF is an accurate reflection of dopamine turnover in the brain. PMID- 8215249 TI - Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. AB - A major theory of aging is that oxidative damage may accumulate in DNA and contribute to physiological changes associated with aging. We examined age related accumulation of oxidative damage to both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in human brain tissue. We measured the oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (OH8dG), in DNA isolated from 3 regions of cerebral cortex and cerebellum from 10 normal humans aged 42 to 97 years. The amount of OH8dG, expressed as a ratio of the amount of deoxyguanosine (dG) or as fmol/micrograms of DNA, increased progressively with normal aging in both nDNA and mtDNA; however, the rate of increase with age was much greater in mtDNA. There was a significant 10-fold increase in the amount of OH8dG in mtDNA as compared with nDNA in the entire group of samples, and a 15-fold significant increase in patients older than 70 years. These results show for the first time that there is a progressive age-related accumulation in oxidative damage to DNA in human brain, and that the mtDNA is preferentially affected. It is possible that such damage may contribute to age-dependent increases in incidence of neurodegenerative diseases. PMID- 8215250 TI - Carbamazepine-induced heart block in a child with tuberous sclerosis and cardiac rhabdomyoma: implications for evaluation and follow-up. AB - We describe a young child with tuberous sclerosis and cardiac rhabdomyoma who developed reversible heart block after being placed on carbamazepine treatment for seizures. Patients of any age with known or suspected intrinsic cardiac disease should be monitored for conduction disturbance if they are treated with carbamazepine. PMID- 8215251 TI - Herpes simplex type 1 encephalitis in acquired immunodeficiency syndrome. AB - A severe acute necrotizing herpes simplex virus type 1 encephalitis, apparently mediated by macrophages or cytokines or both, was seen in a patient with acquired immunodeficiency syndrome. The necrosis had a distribution similar to that seen in immunocompetent subjects. Viral inclusions were abundant and meningeal reaction was minimal, as previously described in one anergic patient. PMID- 8215252 TI - Long-term follow-up of 121 patients with benign fasciculations. AB - Using the case records of Mayo Clinic patients, 121 patients with a diagnosis of benign fasciculations were identified. All had a normal neurological examination and normal electrophysiological studies, except for fasciculation potentials. Interviews by telephone were conducted 2 to 32 years after diagnosis. None of the patients developed symptomatic motor neuron disease. Forty individuals were in health care careers. A subset of 19 patients described acute onset of fasciculations following a viral infection. Benign fasciculations are not a preclude to progressive motor neuron disease. PMID- 8215253 TI - Recurrent ascending myelitis: an unusual presentation of herpes simplex virus type 1 infection. AB - We report on a healthy female with a unique relapsing transverse myelitis accompanied by herpes simplex virus type 1 (HSV-1) infection. Magnetic resonance imaging showed cord enlargement and increased signal intensity on T1-weighted image with gadolinium enhancement from T-4 to T-10 during the first attack and from C-1 to C-2 during the second episode. She was not diagnosed during the first attack. During the second episode, laboratory studies disclosed IgM and IgG antibodies to HSV at the outset with greater than fourfold increases in antibody levels in the serum and cerebrospinal fluid (CSF). Cells cultured from the CSF were positive for HSV-1 according to the immunofluorescence method. The presence of HVS-1 DNA in CSF was documented by polymerase chain reaction (PCR) technique. Acyclovir was given with a partial recovery. We anticipate that PCR assay of CSF will assist early diagnosis of herpetic central nervous system disorders. PMID- 8215254 TI - Ictal single-photon emission computed tomography demonstrates localized epileptogenesis in cortical dysplasia. AB - We investigated the use of ictal single-photon emission computed tomography (SPECT) in 2 children with intractable epilepsy. Ictal scalp electroencephalographic studies failed to localize the epileptic focus and interictal data demonstrated widespread lateralized abnormalities. Ictal SPECT studies with technetium 99m-hexamethylpropyleneamineoxime demonstrated focal areas of hyperperfusion in the frontal lobes. Resection of the abnormal areas shown by SPECT was carried out despite evidence of large areas of epileptogenesis demonstrated by scalp and subdural electroencephalographic studies. Pathological material revealed cortical dysplasia. Ictal SPECT provides functional evidence for localized epileptogenesis in focal cortical dysplasia. PMID- 8215255 TI - Cerebrospinal fluid inhibits Alzheimer beta-amyloid fibril formation in vitro. AB - Alzheimer's disease is characterized by the deposition of beta-protein (A beta) as amyloid. Recently, it was found that A beta is a normal component of serum and cerebrospinal fluid. Synthetic peptides homologous to A beta form amyloid-like fibrils spontaneously in water or physiological solutions. Using a peptide homologous to A beta 1-40, we find that fibril formation is inhibited by the presence of cerebrospinal fluid. PMID- 8215256 TI - Antiparkinson efficacy of deprenyl. DATATOP Steering Committee of Parkinson Study Group. PMID- 8215257 TI - Ethnicity of Scandinavian populations from 1050-1500 A.D. AB - In a skeletal material of five individuals from a non-christian cemetery in Middle Sweden (Vivallen) non-metric traits in skulls and mandibles were studied. Burial gifts and burial customs indicate Saamisch/Lappish origin of these individuals. Their affinities are explored here by comparing the traits with data on crania of Saamish populations from Northern Norway as well a with data of Nordic populations from Middle Sweden and Middle Norway. The Nordic populations from Sweden and Norway are dated to the Medieval period and the Saamish population is post-Medieval. The individuals of the Vivallen burial ground were found to exhibit Saamish as well as Nordic traits. These anthropological investigations together with odontological and palaeopathological studies constitute parts of the South-Saami project, in which also archaeologists from Sweden and Norway participate. PMID- 8215258 TI - [The new growth norm of Czech and Slovakian children and adolescents]. AB - This paper introduces the new growth values of body height and body weight of the Czech and Slovak children and youths aging 1 1/2 to 18 years. This investigation was carried out during 1987-1988 on the whole territory of the Czech and Slovak Federative Republic and includes 47,099 probands. Comparing the older and recent Czech and Slovak body height and body weight data the effects of long-termed and short-termed secular trends are seen. The present-day Slovak children are equal or somewhat taller than the Czech ones. During the period of adolescence they differ, however, from the Czech children. Similar observations are seen in the boys concerning the body weight. The Slovak girls are on the average somewhat lighter than the Czech girls already from the age of nine years onward. The counte poise between Czech and Slovak children and youths are most likely due to the improvement of the nutritional conditions in the Slovak population since the end of World War II. The mean intersexual differences at the end of the adolescent period in Czechs as well as in Slovaks come to 11-12 cm in body height and 12-13 kg in body weight. PMID- 8215259 TI - Secular trend in height in Sardinian conscripts drafted from 1879-1883 to 1983 1986. AB - This paper deals with the secular height trend in Sardinian conscripts. Between 1883 and 1986 an increase in height of 6.77 cm (0.66 cm/decade) was found. On comparing conscripts born in 1948-1949 (immediately after the Second World War) with those born in 1964-1968 one sees an increase in average height of 2.39 cm/decade, with a peak of 3.67 cm/decade in the comparison between subjects born in 1948-1949 and those born in 1955-1958. PMID- 8215260 TI - Biology of aging in an Israeli population. 1. Review of literature and morphological variation analysis. AB - This article reports the results of a comparative morphological assessment carried out on five age segments of an Israeli population: 1. neonates, 2. early school age children (6.5-7.5 years old), 3. young adults (18-29), 4. mature adults (30-45) and 5. elderly people (75-94). The aim of the investigation was to analyze the relationship between developmental homeostasis phenomena and the aging process. Developmental homeostasis was assessed via group coefficient of variation (CV) for 21 morphological traits and fluctuating asymmetry (FA) for 8 bilateral traits. The majority of traits was found to show significantly increased CV and FA in the elderly group. This finding is consistent with the hypothesis that the aging process is accompanied by the total breakdown of the individual's developmental stability. PMID- 8215261 TI - [Sex hormone concentrations and body dimensions of postmenopausal women as correlates of age at menarche]. AB - The present study focused on the correlations between age at menarche and body dimensions as well as sex hormone levels in 142 postmenopausal Austrian women. Statistically significant correlations occurred between the age at menarche and levels of the sex hormones estradiol, progesterone, testosterone and androstenedione as well as several cephalic and post-cephalic length- and height dimensions. Women with a late menarche showed lower sex hormone levels and surpassed women with an early menarche in all length- and height dimensions. Regarding the circumference measures and the amount of subcutaneous fat tissue, no statistically significant correlations with the age at menarche could be observed. Nevertheless the women with an early menarche were more corpulent than women with a late menarche. The fact, that with postmenopausal women no statistically significant correlations between the amount of subcutaneous fat tissue and the age at menarche could be observed is caused by several exogenous factors, like changes in nutritional habits and less physical training in ageing women. PMID- 8215262 TI - Finger dermatoglyphics in Delta de l'Ebre: a Mediterranean Spanish population. AB - Pattern types and quantitative finger dermatoglyphics have been analyzed in a Spanish population samples (141 males, 200 females) from the Mediterranean coast. For both dermatoglyphic traits sexual and bilateral differences were tested by means of Chi-square and Student's t-test. Concerning the pattern types the male samples show an intermediate position in the Spanish variation range, whereas the female sample differs from all the populations compared. In regard of the quantitative values the Delta de l'Ebre population is within the general range of ridge counts described for other Iberian samples. This is valid for both sexes. PMID- 8215263 TI - Role of the mandibular first molar in the development of the supraorbital region in apes and humans. AB - Our previous studies in apes and humans have demonstrated that the development of the supraorbital ridge is a direct consequence of masticatory forces. The smaller the power arm/load arm ratio of the mandible, the greater the force exerted by the temporalis muscle and the larger the supraorbital ridge. The purpose of the present study is to further elucidate the role of the masticatory apparatus, in particular the role of the first mandibular molar. Measurements of the size of the supraorbital ridges in ape skulls and in human skulls from Tuscany, Italy and St. Lawrence Island, Alaska, were determined using parasagittal CAT scans as in our previous studies. For the purpose of this study, the mesio-distal and buccolingual dimensions of the first molar were measured from the actual tooth in all cases. Statistical analysis shows a positive correlation between the mesio distal dimension of the mandibular first molar and the size of the ridge in humans (r = 0.61, p < 0.005) and in apes (r = 0.79, p < 0.01), which explains much of the variation in the size of the supraorbital ridge, 37% (0.61(2)) in humans and 62% (0.79(2)) in apes. The role of the mandibular first molar differs in humans versus apes because of differences in masticatory mechanics. PMID- 8215264 TI - Genetics and mechanisms of glycopeptide resistance in enterococci. PMID- 8215265 TI - Treatment of typhoid fever with ceftriaxone for 5 days or chloramphenicol for 14 days: a randomized clinical trial. AB - To compare the therapeutic efficacy of ceftriaxone given once daily for 5 days and chloramphenicol given four times daily for 14 days, a controlled trial was carried out with 59 patients who were culture positive for Salmonella typhi. Ceftriaxone was given to 28 patients in once-daily intravenous doses of 75 mg/kg of body weight to children and 4 g to adults for 5 days; chloramphenicol was given to 31 patients at a dosage of 60 mg/kg/day until defervescence and then at 40 mg/kg/day to complete 14 days of treatment. All Salmonella isolates were susceptible to both antibiotics. Clinical cures (defervescence without complications, no relapse, and no need for further treatment) occurred in 79% of the patients treated with ceftriaxone and 90% of those treated with chloramphenicol (P = 0.37). On the third day of treatment, blood cultures were positive for S. typhi for 60% of the patients in the chloramphenicol group and 0% of the ceftriaxone group (P = 0.001). Defervescence occurred in half the patients in both groups during the first 7 days, but on days 9 to 13 after the start of treatment, nine patients in the ceftriaxone group, compared with six patients in the chloramphenicol group, remained febrile (P = 0.4). The median hematocrit and total leukocyte counts at day 14 were significantly lower for the chloramphenicol group than those for the ceftriaxone group (P = 0.01 and P = 0.02, respectively). These results indicate that the effects of therapy with ceftriaxone for typhoid fever differed from those of chloramphenicol therapy in that blood cultures became negative earlier, prolonged fever persisted in some patients, and bone marrow suppression was reduced. We conclude that a short, 5-day course of ceftriaxone is a useful alternative to conventional 14-day chloramphenicol therapy in the treatment of typhoid fever. PMID- 8215266 TI - Treatment of hospitalized patients with complicated skin and skin structure infections: double-blind, randomized, multicenter study of piperacillin tazobactam versus ticarcillin-clavulanate. The Piperacillin/Tazobactam Skin and Skin Structure Study Group. AB - We compared the efficacy and safety of two beta-lactam-beta-lactamase inhibitor combinations, namely, piperacillin-tazobactam and ticarcillin-clavulanate, in the treatment of complicated bacterial infections of skin that required hospitalization. The study was a randomized, double-blind, comparative trial involving 20 centers. The infections were classified as (i) cellulitis with drainage, (ii) cutaneous abscess, (iii) diabetic or ischemic foot infection, and (iv) infected wounds and ulcers with drainage. The clinical response rates were comparable for the two treatment regimens (61% of the patients were cured with piperacillin-tazobactam and ticarcillin-clavulanate and improvement was seen in 15 and 16% of patients treated with piperacillin-tazobactam and ticarcillin clavulanate, respectively). Both regimens were found to be safe and well tolerated. These data support the use of piperacillin-tazobactam for initial empiric therapy of hospitalized patients with complicated skin and skin structure infections. PMID- 8215267 TI - Randomized trial comparing ceftriaxone with cefonicid for treatment of spontaneous bacterial peritonitis in cirrhotic patients. AB - We compared cefonicid (2 g every 12 h) and ceftriaxone (2 g every 24 h) for their efficacy and safety in treating spontaneous bacterial peritonitis in cirrhotic patients in an open randomized clinical trial (30 patients in each group). Clinical, laboratory, and bacteriologic characteristics were similar in both groups. Ceftriaxone-susceptible strains were isolated on 44 occasions (94%), and cefonicid-susceptible strains were isolated on 43 occasions (91.5%). The antibiotic concentration in ascitic fluid/MIC ratio for ceftriaxone was > 100 throughout the dose interval (24 h), while it was lower for cefonicid (between 1 and 18). A total of 100% of patients treated with ceftriaxone, and 94% of those treated with cefonicid were cured of their infections (P was not significant). Hospitalization mortality was 37% in the cefonicid group and 30% in the ceftriaxone group (P was not significant). The time that elapsed between the initiation of treatment and the patient's death was shorter in the cefonicid group patients (5.3 +/- 3.90 days) than in the ceftriaxone group patients (11.8 +/- 9.15 days) (P < 0.05). None of the patients presented with superinfections, and only two patients treated with cefonicid and three patients treated with ceftriaxone developed colonizations with Enterococcus faecalis or Candida albicans. Ceftriaxone and cefonicid are safe and useful agents for treating cirrhotic spontaneous bacterial peritonitis, although the pharmacokinetic characteristics of ceftriaxone seem to be more advantageous than those of cefonicid. PMID- 8215268 TI - WIN 54954 treatment of mice infected with a diabetogenic strain of group B coxsackievirus. AB - The therapeutic efficacy of an experimental antiviral agent, WIN 54954, was evaluated in a mouse model in which infection by coxsackievirus B4 (CVB4) strain E2 was followed by diabetes mellitus. Male CD1 mice (age, 5 weeks) were inoculated with 10(4) PFU of CVB4. WIN 54954 was administered orally via gavage tube in a dose of either 5 or 50 mg/kg of body weight per day. Treatment was initiated on the day of inoculation and was continued for 10 days. Control animals received the xanthan gum carrier only. At 3 days postinoculation (p.i.), the mean titer of virus in the pancreas was found to be significantly lower in both the high-dose (P < 0.001) and low-dose (P < 0.05) treatment groups compared with that in the controls. Furthermore, islet histologic abnormalities were significantly less common in the high-dose group (P < 0.02) than in the controls. At 7 weeks p.i., both fasting and 1-h postprandial glucose levels in blood were significantly lower for both the high-dose (P < 0.001) and the low-dose (P < 0.01) treatment groups than in controls. The proportion of mice with persistent viral RNA in the pancreas at this time, as detected by polymerase chain reaction, was significantly reduced in the high-dose treatment group (4 of 11 mice) compared with that in the controls (7 of 8 mice). When mice received 50 mg of WIN 54954 per kg daily beginning at either 48 or 72 h postinoculation, the titers in the pancreas were again significantly reduced at 3 days p.i. compared with those in the controls (P < 0.01 and P < 0.05, respectively). Thus, WIN 54954 effectively reduces virus replication and islet histologic changes acutely and decreases, at 7 weeks, both the metabolic alteration associated with diabetes mellitus and the incidence of detectable viral RNA in the pancreas. PMID- 8215269 TI - Effect of increased dosages of amoxicillin in treatment of experimental middle ear otitis due to penicillin-resistant Streptococcus pneumoniae. AB - A gerbil model of acute middle ear otitis was used to evaluate the efficacy of increased dosages of amoxicillin in eradicating infection induced by penicillin resistant Streptococcus pneumoniae. Three different strains were used: (i) a serotype 23 penicillin-susceptible strain; (ii) a serotype 23 penicillin resistant strain (MIC of penicillin, 2 micrograms/ml); and (iii) a serotype 19 highly penicillin-resistant strain (MIC of penicillin, 4 to 8 micrograms/ml). Animals were inoculated bilaterally with 10(7) CFU per ear by transbulla challenge and treated 2 to 4 h postinfection by amoxicillin administrated subcutaneously. The course of the disease was monitored bacteriologically on days 2, 4, and 8 postinfection. The three strains had a similar pathogenicity in untreated animals in terms of the duration of the disease, bacterial counts in middle ear (ME) fluid, and systemic complications. Infection due to the penicillin-susceptible strain was cured after two injections of 2.5 mg/kg of body weight. No bacteria were recovered at day 2 after two injections at 10 and 25 mg/kg with the penicillin-resistant and highly penicillin-resistant strains, respectively. Under these experimental conditions, increased does of amoxicillin consistent with MICs were able to clear ME infection. Pharmacokinetic parameters of amoxicillin in serum and ME fluid were within the clinical range at the doses used in the study. PMID- 8215270 TI - A gene conferring resistance to vancomycin but not teicoplanin in isolates of Enterococcus faecalis and Enterococcus faecium demonstrates homology with vanB, vanA, and vanC genes of enterococci. AB - We report the sequence of a 630-bp fragment of a gene associated with resistance to high levels of vancomycin in a clinical isolate of Enterococcus faecalis which retained susceptibility to teicoplanin. This gene was similar to the recently sequenced vanB and partially homologous with vanA, but it showed less-marked similarity to vanC. A DNA probe, derived from this polymerase chain reaction amplified gene fragment, hybridized specifically with genomic DNA from Enterococcus faecium and E. faecalis isolates which were vancomycin resistant (MICs ranged from 8 to 512 micrograms/ml) but susceptible to teicoplanin. Curing of vancomycin resistance was associated with loss of DNA hybridization with the gene probe. Transfer of DNA which hybridized with the probe accompanied transfer of vancomycin resistance to a susceptible recipient strain. Neither curing nor transfer of vancomycin resistance was consistently related to loss or acquisition, respectively, of plasmid DNA. PMID- 8215271 TI - Effect of zidovudine on preimplantation murine embryos. AB - It previously has been demonstrated that zidovudine (AZT) is lethal to early murine embryos. The effect of the drug on pre- and postimplantation embryos was examined to delineate the timing of this toxicity and to investigate its possible mechanisms. Embryos exposed in the whole mouse during preblastocyst development were unable to proceed beyond the blastocyst stage. Similarly, when two-cell embryos harvested from unexposed females were exposed to low-concentration (1 microM) AZT in vitro over 24 h, development beyond the blastocyst stage was inhibited. In contrast, drug exposure during in vitro blastocyst and postblastocyst development resulted in little or no morphologic toxicity. Further investigation revealed that preblastocyst AZT exposure resulted in the development of blastocysts with significantly lower cell numbers than control embryos. While embryonic exposure to AZT at the blastocyst and postblastocyst stages also resulted in retarded cell division, the effects were milder than those recorded after preblastocyst exposure. These data demonstrate that the critical period of AZT toxicity toward murine embryos is between ovulation and implantation and indicate that AZT directly suppresses cell division in the preimplantation embryo. PMID- 8215272 TI - Modification of the C terminus of cecropin is essential for broad-spectrum antimicrobial activity. AB - Cecropin A is a naturally occurring peptide with bactericidal activity against gram-negative and gram-positive bacteria. Production of large quantities of bactericidal peptides that are similar in structure and activity to cecropin A has been achieved by combining recombinant DNA techniques and techniques and chemical modification. Expression of the bactericidal peptide in Escherichia coli was accomplished through the formation of a fusion protein. The 5' end of the L ribulokinase gene was fused to a single copy of a synthetic gene encoding cecropin A. A methionine codon was engineered between the two genes, and a methionylglycine extension was introduced at the C terminus of cecropin A. Cyanogen bromide treatment of the fusion protein yielded cecropin A with a C terminal homoserine. The recombinant cecropin A with a homoserine at the C terminus did not kill most gram-positive bacteria tested. However, recombinant cecropin A with a chemically modified C terminus has antimicrobial activity similar to that of cecropin produced by cecropia pupae. PMID- 8215273 TI - Cefprozil versus penicillin V in treatment of streptococcal tonsillopharyngitis. AB - In a randomized multicenter study, the efficacy and safety of cefprozil were compared with those of penicillin in the treatment of group A streptococcal tonsillopharyngitis in children. Of the 409 patients enrolled, 323 were evaluable for their clinical and bacteriological responses; of these 323 children, 172 received cefprozil and 151 received penicillin V. The clinical responses in patients treated with cefprozil were significantly better than those in patients who received penicillin (95.3 versus 88.1%; P = 0.023). Eradication of the original serotype of group A streptococci was achieved in 91.3% of patients treated with cefprozil and 87.4% of patients treated with penicillin, the difference not being statistically significant (P = 0.125). However, there were significantly more symptomatic patients among the bacteriological failures in the penicillin group (68.4%) than in the cefprozil group (26.7%). beta-Lactamase producing Staphylococcus aureus was more frequently isolated from the throat flora during penicillin therapy than during cefprozil treatment. No difference in the incidence of adverse events probably related or of unknown relationship to the study drugs was observed in the two treatment groups (5.2% of those treated with cefprozil and 6.0% of those treated with penicillin). Cefprozil can be considered a safe and reliable drug for the treatment of streptococcal pharyngitis in children. PMID- 8215274 TI - Detection of tetracyclines and efflux pump inhibitors. AB - Screening assays for the detection of tetracyclines and inhibitors of tetracycline efflux pumps are described. The tetracycline assay is based on the observation that the tetA(B) gene encoding the efflux pump of transposon Tn10 is induced by tetracycline. The Escherichia coli strain designed to detect tetracyclines contains a single copy of a tetA(B)-lacZ transcriptional fusion integrated into the chromosome and the tetR gene encoding the tetracycline repressor on a plasmid. The assay specifically detects tetracyclines of distinct structures, but not other classes of drugs. A strain capable of detecting inhibitors of the TetA(B) efflux pump contained the tetA(B)-lacZ fusion and, in addition, a tetA(B) structural gene lacking its transcriptional regulatory signals which mediated resistance to only 5 micrograms of tetracycline per ml. This strain was more refractory to induction by tetracycline because of the action of the pump. Inhibitors were detected in two ways: (i) beta-galactosidase induction in the presence of 5 ng of tetracycline per ml, a subinducing concentration, and (ii) growth inhibition in the presence of 5 micrograms of tetracycline per ml. A strain designed to detect inhibitors of the Tet(K) efflux pump from Staphylococcus aureus was constructed by substituting the tet(K) structural gene for the tetA(B) gene. Nocardamine and other siderophores were found to interfere with the action of tetracycline efflux pumps. PMID- 8215276 TI - OXA-11, an extended-spectrum variant of OXA-10 (PSE-2) beta-lactamase from Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa ABD, which was isolated in October 1991 from blood cultures of a burn patient in Turkey, was resistant to cephalosporins, particularly ceftazidime (MIC, 512 micrograms/ml), penicillins, aztreonam, and meropenem, but not to imipenem. Cephalosporin and penicillin resistance transferred to P. aeruginosa PU21 and was associated with a beta-lactamase with a pI of 6.4 encoded by a 100-MDa plasmid designated pMLH52. Like extended-spectrum TEM and SHV beta-lactamases, this enzyme hydrolyzed penicillins and newer cephalosporins but did not hydrolyze cefoxitin or carbapenems. However, it differed from TEM and SHV derivatives in being a potent oxacillinase, and its encoding gene did not hybridize with probes to TEM and SHV genes. To characterize the enzyme, libraries of total DNA were cloned into plasmid pUC19 and were transformed into Escherichia coli DH5 alpha. Recombinant plasmids that gave ceftazidime resistance all contained a 3.65-kb BamHI fragment. Deletions from this fragment allowed the beta-lactamase gene to be located on a 1.4-kb section of DNA, which contained an open reading frame of 798 bases. This encoded a protein that was deduced to differ from PSE-2 beta-lactamase only in having serine instead of asparagine at position 143 and aspartate instead of glycine at position 157. It is concluded that the resistance of isolate ABD dependent on an extended-spectrum variant of the PSE-2 enzyme. The ability of this enzyme to cause ceftazidime resistance dependent primarily on a low Km for the compound; Vmax remained low. It is proposed that PSE-2 should be transferred to the OXA group as OXA-10 and that the new enzyme be designated OXA-11. PMID- 8215275 TI - Evaluation of antimicrobial regimens for treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. AB - The most appropriate therapy for meningitis caused by Streptococcus pneumoniae strains resistant to the extended-spectrum cephalosporins is unknown. We evaluated ceftriaxone, vancomycin, and rifampin alone and in different combinations and meropenem, cefpirome, and clinafloxacin alone in the rabbit meningitis model. Meningitis was induced in rabbits by intracisternal inoculation of one of two pneumococcal strains isolated from infants with meningitis (ceftriaxone MICs, 4 and 1 microgram/ml, respectively). Two doses, 5 h apart, of each antibiotic were given intravenously (except that ceftriaxone was given as one dose). Cerebrospinal fluid bacterial concentrations were measured at 0, 5, 10, and 24 h after therapy was started. Clinafloxacin was the most active single agent against both strains. Against the more resistant strain, ceftriaxone or meropenem alone was ineffective. The combination of vancomycin and ceftriaxone was synergistic, suggesting that this combination might be effective for initial empiric therapy of pneumococcal meningitis until results of susceptibility studies are available. PMID- 8215277 TI - Use of rifabutin in treatment of systemic Mycobacterium paratuberculosis infection in mice. AB - BALB/c mice were infected intraperitoneally with Mycobacterium paratuberculosis and, after allowing the infection to progress for 30 days, were treated with rifabutin at 0, 12.5, 25, and 50 mg/kg of body weight. Rifabutin was administered in drinking water under conditions of water deprivation, whereby the entire daily dose was delivered within a 1-h period. Animals were killed at biweekly intervals from time zero of treatment to 180 days. Spleens and livers from each animal were examined by quantitative bacteriologic culture and histopathology. Restricted water availability was found to be a viable alternative to daily gavage for single-dose bolus administration. Infection, as assessed by bacterial counts, was reduced only in animals that received 50 mg of rifabutin per kg. In these animals, bacterial counts in the liver and spleen were reduced from 7.2 x 10(5) +/- 4.1 x 10(4) and 6.5 x 10(5) +/- 4.1 x 10(4) to 3.0 x 10(3) +/- 1.8 x 10(2) and 3.1 x 10(3) +/- 2.2 x 10(2), respectively, over the 6-month treatment period. Rifabutin may be an appropriate chemotherapeutic drug for long-term treatment of M. paratuberculosis infection and should be considered in any multidrug regimen. PMID- 8215278 TI - Susceptibilities of 428 gram-positive and -negative anaerobic bacteria to Bay y3118 compared with their susceptibilities to ciprofloxacin, clindamycin, metronidazole, piperacillin, piperacillin-tazobactam, and cefoxitin. AB - The susceptibilities of 428 gram-negative and gram-positive anaerobes (including selected cefoxitin-resistant strains) to Bay y3118 (a new fluoroquinolone), ciprofloxacin, clindamycin, metronidazole, cefoxitin, piperacillin, and piperacillin-tazobactam were tested. Organisms comprised 115 Bacteroides fragilis group, 116 non-B. fragilis Bacteroides, Prevotella, and Porphyromonas spp., 40 fusobacteria, 58 peptostreptococci, 48 gram-positive non-spore-forming rods, and 51 clostridia. beta-Lactamase production was demonstrated in 87% of the gram negative rods but in none of the gram-positive organisms. Overall, Bay y3118 was the most active agent, with all organisms inhibited at an MIC of < or = 2.0 micrograms/ml (MICs for 50% [MIC50] and 90% [MIC90] of strains tested, 0.125 and 0.5 microgram/ml, respectively). By contrast, ciprofloxacin was much less active, with only 42% of strains susceptible at a breakpoint of 2.0 micrograms/ml (MIC50, 4.0 micrograms/ml; MIC90, 16.0 micrograms/ml). Metronidazole was active against all gram-negative rods, but 7% of peptostreptococci, 83% of gram-positive non spore-forming rods, and 4% of non-Clostridium perfringens, non-Clostridium difficile clostridia were resistant to this agent (MICs, > 16.0 micrograms/ml). Clindamycin was active against 94% of Bacteroides, Prevotella, and Porphyromonas spp., 91% of peptostreptococci, and 100% of gram-positive non-spore-forming rods, but was active against only 70% of fusobacteria and 53% of clostridia. Cefoxitin was active against > or = 90% of all groups except the B. fragilis group and non Propionibacterium acnes gram-positive non-spore-forming rods (both 85%) and C. difficile (20%). Significant enhancement of piperacillin by tazobactam was seen in all beta-lactamase-positive strains (99% susceptible; MIC90, 8.0 micrograms/ml), and all beta-lactamase-negative strains were susceptible to piperacillin (MIC90, 8.0 micrograms/ml). Clinical studies are required to delineate the role of Bay y3118 in the treatment of anaerobic infections. PMID- 8215279 TI - Controlled trial to evaluate protection of high-risk infants against respiratory syncytial virus disease by using standard intravenous immune globulin. AB - We performed a randomized, controlled trial of intravenous immune globulin (respiratory syncytial virus [RSV] neutralizing [Nt] antibody titer of 1:950 in 5% solution) to evaluate protection against RSV-induced disease over two respiratory virus seasons. Forty-nine children (mean age at enrollment, 4.5 months) with severe congenital heart disease or bronchopulmonary dysplasia were randomized as follows. Twenty-four patients were followed as controls and received no immune globulin. Twenty-five patients received monthly infusions of immune globulin at a dose of 500 mg/kg of body weight. There was a similar distribution between groups of patients with heart disease and bronchopulmonary dysplasia. There were 12 culture-proven RSV infections, 6 in the prophylaxis group and 6 in the control group. There was a trend toward less severe RSV illness in immune globulin recipients, as measured by length of hospitalization. Four of the six immune globulin recipients were hospitalized for a total of 35 days (mean, 8.8 +/- 5.0 days) because of RSV illness, in contrast to 51 hospital days (mean, 12.8 +/- 7.6 days) among RSV-infected controls. We conclude that monthly infusions of standard immune globulin containing RSV Nt antibodies may be safely administered to high-risk children, but that standard intravenous immune globulin does not contain sufficient RSV Nt antibody titer to fully protect against severe RSV illness. PMID- 8215280 TI - Antimicrobial resistance in human oral and intestinal anaerobic microfloras. AB - In the present study we determined the resistance patterns of anaerobic bacteria from human saliva and stool specimens and investigated whether there were significant differences in resistance between outpatients and hospitalized patients, regardless of whether they had received antimicrobial agents. No bacterial strains resistant to ampicillin, piperacillin, cefoxitin, cefuroxime, imipenem, clindamycin, doxycycline, chloramphenicol, or metronidazole were isolated from the saliva samples. However, resistance to ampicillin, cefoxitin, and cefuroxime was found in strains from 70% of the fecal samples (mainly Bacteroides thetaiotaomicron, Clostridium innocuum, and Bacteroides ovatus). Resistance to both ampicillin and cefuroxime was frequently found in 19% of the isolated strains (mainly B. thetaiotaomicron, B. ovatus, and Bacteroides vulgatus). No strains that were resistant to imipenem, chloramphenicol, or metronidazole were found. Hospitalization and/or intake of antimicrobial agents was associated with an increase in the relative number of resistant anaerobic intestinal bacteria. The percentage of resistant anaerobic strains encountered, compared with the total number of anaerobic bacteria in the normal fecal microflora, was between 5.2 and 14.8%, with the lower value associated with the outpatient group. Two-thirds of the resistant strains from this group had a relative frequency of less than 1% of the total anaerobic flora, while one-third of the strains were present at a level of greater than 1%; for the hospitalized patients, two-thirds of the strains were present at a level of greater than 1%, and one-third of the strains were present at a level of less than 1% (P < 0.001). Patients who had received antimicrobial agents for 6 days or more (n=20) had an average of 1.6 resistant anaerobic strains each, while patients treated for 3 to 5 days (n = 30) had a mean number of 0.87 resistant strains each ( P < 0.05). PMID- 8215281 TI - Comparison of ciprofloxacin and ceftriaxone as single-dose therapy for uncomplicated gonorrhea in women. AB - Although women bear the brunt of gonococcal infection-related morbidity, few large studies of gonorrhea treatment in women have been conducted. In a multicenter, double-blind, placebo-controlled trial, 181 evaluable women with uncomplicated gonorrhea were treated with ciprofloxacin (250 mg orally; 94 women) or ceftriaxone (250 mg intramuscularly; 87 women). Twenty-four percent of the participants were infected with antibiotic-resistant Neisseria gonorrhoeae. Cervical gonorrhea was cured in 100% (93 of 93) of the women treated with ciprofloxacin and 99% (83 of 84) receiving ceftriaxone. All pharyngeal (n = 5) or rectal (n = 20) infections treated with ciprofloxacin were cured, as were ceftriaxone-treated patients with pharyngeal (n = 6) or rectal (n = 21) infection. Geometric mean MICs (range) for 248 pretreatment isolates were: penicillin, 0.28 (0.015 to 8.0); tetracycline, 0.46 (0.06 to 4); ciprofloxacin, 0.003 (0.002 to 0.015); and ceftriaxone, 0.004 (0.001 to 0.125) microgram/ml. Both drugs were well tolerated. Despite the high prevalence of antibiotic resistant gonococci in these populations, 250 mg of oral ciprofloxacin was as effective as an injection of ceftriaxone. PMID- 8215282 TI - Development and characterization of a rapid screening assay for identifying antipneumocystis agents. AB - We developed a rapid assay for screening of compounds with potential antipneumocystis activity on the basis of incorporation of [35S]methionine into proteins newly synthesized by Pneumocystis carinii. Unambiguous evidence that P. carinii synthesizes proteins in vitro was provided by immunoprecipitation studies demonstrating the incorporation of [35S]methionine into the major surface glycoprotein. Treatment with two clinically active antipneumocystis agents, atovaquone (10(-4) M) or pentamidine (10(-4) M), prevented this incorporation. Total [35S]methionine incorporation paralleled incorporation into the major surface glycoprotein, permitting rapid assessment of anti-P. carinii activity by scintillation counting. Treatment with pentamidine (1 x 10(-4) M), atovaquone, trimethoprim (1 x 10(-4) M)-sulfamethoxazole (7.9 x 10(-4) M), piritrexim (1 x 10(-7) M), RO11-8958 (1 x 10(-4) M), and amphotericin B (1 microgram/ml) resulted in a greater than 67% inhibition (P < 0.05) of [35S]methionine incorporation. No decrease in [35S]methionine incorporation was seen with dapsone (10(-5) M), trimethoprim (10(-4) M), recombinant mouse tumor necrosis factor (500 ng/ml), or gamma interferon. This rapid in vitro assay should be a useful adjunct in the development of new antipneumocystis agents. PMID- 8215283 TI - Therapy of human hydatid disease with mebendazole and albendazole. AB - We report our experience in the treatment with benzoimidazole carbamates (mebendazole and albendazole) of 337 patients affected by hydatid cysts with different localizations. The treated cysts showed degenerative modifications in 50.6% of the cases after mebendazole treatment and in about 80% after albendazole treatment. Relapses after therapy were observed in 30% of the cases; about 95% of the recurring cysts showed good susceptibility to a further cycle of therapy with benzoimidazole carbamates. Side effects observed with either drug were not severe and always reversible, consisting mainly of abdominal pains and increased levels of transaminases in serum. Among the factors that may influence the therapeutic results are the drug employed, the age of the cysts, the age of the patient, and the localization of the cysts and their morphological characteristics. Moreover, it can be hypothesized that each hydatid cyst has an intrinsic sensitivity to benzoimidazole carbamates. PMID- 8215284 TI - Mathematical model for comparison of time-killing curves. AB - The relevance of mathematical modeling to investigations of the bactericidal effects of antimicrobial agents has been emphasized in many studies of killing kinetics. We propose here a descriptive model of general use, with four parameters which account for the lag phase, the initial number of bacteria, and the limit of effectiveness and bactericidal rate of antimicrobial agents. The model has been applied to several kinetic datum sets with amoxicillin, cephalothin, nalidixic acid, pefloxacin, and ofloxacin against two Escherichia coli strains. It is a useful tool to compare killing curves by taking into account model parameter confidence limits. This can be illustrated by studying drug effects, strain effects, and concentration effects. For the antibiotics used here, concentration effects had an influence mainly on the length of the lag phase and the minimum number of living cells observed. It is therefore clear that differences in the killing curves with changes in one or more parameters could occur. PMID- 8215285 TI - Clarithromycin, minocycline, and rifabutin treatments before and after infection of C57BL/6 mice with Mycobacterium avium. AB - C57BL/6 mice were pretreated with rifabutin or clarithromycin alone or combined with minocycline 3 days before intravenous challenge (day 0) with Mycobacterium avium. Treatment was continued until sacrifice at days 1, 8, 15, and 21. Rifabutin or clarithromycin decreased the level of infection in both the lungs and the spleen. Rifabutin was as effective as clarithromycin in the lungs but was less [corrected] effective in the spleen. The clarithromycin-minocycline combination was as effective as clarithromycin alone. PMID- 8215286 TI - Multicenter comparison of in vitro activities of FK-037, cefepime, ceftriaxone, ceftazidime, and cefuroxime. AB - In a multicenter study, the MICs of FK-037 for 90% of the strains tested (MIC90s) were < or = 1 microgram/ml for members of the family Enterobacteriaceae other than Citrobacter freundii, Enterobacter spp., and Serratia marcescens. Activity against Pseudomonas aeruginosa was variable, with a MIC50 and a MIC90 of 4 and 32 micrograms/ml, respectively. Relative to cefepime, however, FK-037 was less active against ceftazidime-resistant isolates of Enterobacter cloacae. The MIC90 of FK-037 for methicillin-resistant staphylococci was > 16 micrograms/ml. PMID- 8215287 TI - Inhibition of Toxoplasma gondii protein synthesis by azithromycin. AB - Azithromycin was shown to specifically inhibit the protein synthesis of Toxoplasma gondii in experimental systems by using free tachyzoites and T. gondii infected mouse macrophages. RNA synthesis of the parasite was not affected by azithromycin. Inhibition of protein synthesis was also proportional to the relative anti-Toxoplasma activity of three macrolides. PMID- 8215288 TI - Comparative in vitro activities of clarithromycin, azithromycin, and erythromycin against Borrelia burgdorferi. AB - The in vitro activities of the macrolide antibiotics clarithromycin, 14-hydroxy clarithromycin, azithromycin, and erythromycin against 19 isolates of Borrelia burgdorferi were investigated. MICs ranged from 0.003 to 0.03 microgram of clarithromycin per ml, 0.007 to 0.03 microgram of 14-hydroxyclarithromycin per ml, 0.003 to 0.03 microgram of azithromycin per ml, and 0.007 to 0.06 microgram of erythromycin per ml. Time-kill studies using the B31 strain of B. burgdorferi demonstrated a > or = 3-log10-unit killing after 72 h with each of the macrolide antibiotics tested in concentrations representing twice the respective MICs. PMID- 8215289 TI - Synthesis and virucidal activity of a water-soluble, configurationally stable, derivatized C60 fullerene. AB - The bis(monosuccinimide) derivative of p,p'-bis(2-aminoethyl)diphenyl-C60 (compound 1), prepared by the fulleroid route, is active against human immunodeficiency virus type 1 (HIV-1) and HIV-2 (50% effective concentration [EC50] averaging approximately 6 microM) in acutely or chronically infected human lymphocytes and is active in vitro against 3'-azido-3'-deoxythymidine-resistant HIV-1 (EC50, approximately 3 microM). The virucidal properties of compound 1 were confirmed by virus inactivation assays. Compound 1 was noncytotoxic up to 100 microM in peripheral blood mononuclear cells and H9, Vero, and CEM cells. In cell free assays, whereas the fullerene showed comparable activity against HIV-1 reverse transcriptase and DNA polymerase alpha (50% inhibitory concentration of approximately 5 microM), it demonstrated selective activity against HIV-1 protease. PMID- 8215290 TI - In vivo effects of rufloxacin and ciprofloxacin on T-cell subsets and tumor necrosis factor production in mice infected with Bacteroides fragilis. AB - We investigated the in vivo effects of rufloxacin and ciprofloxacin on T-cell subsets and tumor necrosis factor production in mice infected with Bacteroides fragilis. These quinolones did not alter the helper/suppressor ratio but did modulate the kinetics of tumor necrosis factor production in infected animals. This result correlated with the observed therapeutic efficacies of the quinolones. PMID- 8215291 TI - Activity of cationically substituted bis-benzimidazoles against experimental Pneumocystis carinii pneumonia. AB - On the basis of a previously observed correlation between the antimicrobial activity and DNA binding strength of dicationic molecules, a series of 10 dicationically substituted bis-benzimidazoles were tested for activity in the rat model of Pneumocystis carinii pneumonia. One of the compounds, 1,4-bis[5-(2 imidazolinyl)-2-benzimidazolyl]butane, was found to be more potent and less toxic than pentamidine. PMID- 8215292 TI - Antibiotic susceptibility of group A streptococci: a 6-year follow-up study. AB - The susceptibility patterns of group A streptococci over the last 6 years in our hospital were determined. Since our last study, carried out in 1987, all isolates have remained very susceptible in vitro to penicillin and all of the other beta lactam agents tested. We observed resistance to erythromycin, clindamycin, tetracycline, and ofloxacin. The prevalence of erythromycin-resistant group A streptococci did not change appreciably throughout the study period. PMID- 8215293 TI - In vitro postantibiotic effect following repeated exposure to imipenem, temafloxacin, and tobramycin. AB - The postantibiotic effect (PAE) following three consecutive 2-h exposures to imipenem, temafloxacin, and tobramycin was determined in Pseudomonas aeruginosa. A PAE and a bactericidal effect were consistently observed for imipenem following each cycle of drug exposure and regrowth. In contrast, the PAE increased with repeated exposure with temafloxacin (1.8 to > 5 h), but disappeared with tobramycin by the third exposure (0.9 to 0 h). These data show that the in vitro PAE may change within a strain following multiple cycles of drug exposure and bacterial regrowth. PMID- 8215294 TI - Susceptibilities of Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum to a new quinolone, OPC 17116. AB - The susceptibilities of human mycoplasmas to OPC 17116 (Otsuka America Pharmaceutical, Inc., Rockville, Md.) and temafloxacin (Abbott Laboratories, Chicago, Ill.) were determined by the agar dilution method and were compared with those to sparfloxacin and ofloxacin. The MICs of OPC 17116 for 90% of Mycoplasma pneumoniae (0.25 microgram/ml) and Mycoplasma hominis (0.125 micrograms/ml) isolates tested were closely similar to those of sparfloxacin and were four- to eightfold greater than those of ofloxacin. Temafloxacin was two- to fourfold more active than ofloxacin. Ureaplasma urealyticum was less susceptible; the MICs of OPC 17116 and temafloxacin for 90% of isolates tested were 2 and 4.0 micrograms/ml, respectively. PMID- 8215295 TI - Isolation of moderately penicillin-susceptible strains of Neisseria meningitidis in Argentina. AB - Four strains that were moderately susceptible to penicillin and/or ampicillin were found among 54 consecutive isolates of meningococci recovered from patients in one pediatric hospital in Argentina from October 1991 to December 1992. Disk diffusion tests performed with 2 U of penicillin failed to detect one strain. These findings suggest that attention should be paid to changes in the susceptibility patterns of meningococci in order to anticipate therapeutic failures in the future. PMID- 8215296 TI - Dental amalgam and multiple antibiotic resistance: an untested hypothesis. PMID- 8215297 TI - Inhibition of HIV-1 replication in cultured cells with phosphorylated dideoxyuridine derivatives encapsulated in immunoliposomes. AB - Among the 2',3'-dideoxynucleoside 5'-triphosphates containing a physiological base, 2',3'-dideoxyuridine 5'-triphosphate (ddUTP) has been reported to be among the most powerful inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT) in cell-free systems. However, in contrast to other dideoxynucleosides, 2',3'-dideoxyuridine (ddU) is inactive in treatment of HIV infected cells in culture, since it is a poor substrate for cellular nucleoside kinases. This problem cannot be overcome by the use of phosphorylated ddU because such compounds are unable to cross cell membranes. To promote entry and thus bypass the limiting steps of intracellular phosphorylation, we have encapsulated mono- and tri-phosphorylated ddU in liposomes coupled to monoclonal antibodies (immunoliposomes). We investigated antiviral effects in two human T cell lines (MT-4, CEM). We observed that ddU nucleotides remain phosphorylated for several weeks after encapsulation in immunoliposomes, and potent antiviral activity is obtained when these drugs are delivered into infected cells by cell-specific antibodies (ED50 < or = 1 microM on CEM). In contrast, no inhibition was observed with non-targeted liposomes containing phosphorylated ddU, or with empty liposomes, whether targeted or not. PMID- 8215298 TI - Inhibitory activity of S-adenosylhomocysteine hydrolase inhibitors against human cytomegalovirus replication. AB - Various acyclic and carbocyclic adenosine analogues, which are apparently targeted at the S-adenosylhomocysteine (AdoHcy) hydrolase have been reported to inhibit the replication of a number of pox-, rhabdo-, paramyxo-, arena-, and reoviruses. Here we show that this activity spectrum extends to human cytomegalovirus (HCMV). Of the compounds tested, neplanocin A, 3-deazaneplanocin A, 6'-C-methylneplanocin A and 5'-noraristeromycin were found to be the most potent inhibitors of HCMV replication in vitro. Their 50% inhibitory concentration ranged from 0.05 to 1.35 micrograms/ml. In general, the anti-HCMV activity of the adenosine analogues correlated well with their affinity (Ki) for AdoHcy hydrolase, suggesting that AdoHcy hydrolase may be considered as a target enzyme for anti-HCMV agents. For four compounds (3-deazaneplanocin A, 6'-C methylneplanocin A (isomers I and II) and 3-deazaadenosine), anti-HCMV potency was greater than could be expected solely from their interaction with AdoHcy hydrolase, suggesting that these compounds may be functioning by an additional mechanism. PMID- 8215299 TI - The subclass IgG responses of mice to influenza surface proteins formulated into liposomes. AB - Unprimed mice and mice primed by prior infection with an H1N1 subtype of influenza virus were used to assess the total and subclass IgG serum antibody responses to influenza virus A/Sichuan/2/87 (H3N2) surface haemagglutinin and neuraminidase proteins incorporated into four different formulations of liposomes. Only one of these liposome preparations, DSPC(B), induced greater total IgG, and subclass IgG1 and IgG2a antibody levels, in sera from both primed and unprimed mice than the aqueous A/Sichuan surface preparations alone administered at equivalent levels of haemagglutinin protein. The same DSPC(B) liposome formulation of A/Sichuan antigens was also the only preparation found to elicit levels of IgG2b and IgG3 subclass antibodies above baseline values in these animals. PMID- 8215300 TI - Intravascular distribution of zidovudine: role of plasma proteins and whole blood components. AB - Knowledge of drug protein-binding and blood cell partitioning may be important for evaluating the pharmacokinetic parameters of zidovudine, particularly because of its intracellular site of action and potential to induce side effects. Equilibrium dialysis studies of zidovudine were performed over 2 h to identify the extent and site of binding. Zidovudine was added to anticoagulated whole blood to study blood cell distribution over a 24 h period at 37 degrees C and at 21 degrees C. Concurrent plasma and whole blood samples were determined at various time-points and blood partitioning was determined by application of a mass balance equation. All samples were analyzed using radioimmunoassay. The free fraction of zidovudine at a concentration of 500 ng/ml (1.7 microM) was 0.77 +/- 0.05 in plasma, 0.78 +/- 0.03 in serum, 0.88 +/- 0.03 in 4 g/dl albumin solution, and 1.0 in 100 mg/dl alpha 1-acid glycoprotein solution. A free fraction of 0.72 +/- 0.10 was observed in plasma from HIV-infected patients with zidovudine concentrations ranging from 16 to 91 ng/ml. Zidovudine equilibration between plasma and blood cells occurred rapidly, being complete within 10 min. After equilibrium was complete, the mean whole blood:plasma ratio was 0.86 +/- 0.02 and 0.80 +/- 0.04 (P = 0.20) and mean blood cell Partitioning ratio, [cell]/[plasma free], was 0.85 +/- 0.06 and 0.66 +/- 0.14 (P = 0.25) for studies at 37 degrees C and 21 degrees C, respectively. The partitioning ratio was relatively consistent over the study period, suggesting no accumulation in blood cells. These results suggest that zidovudine binds to a small extent primarily to albumin. The free concentration equilibrates readily between blood cells and plasma independent of concentration and without signs of accumulation. PMID- 8215302 TI - Efficacy of ganciclovir in combination with zidovudine against cytomegalovirus in vitro and in vivo. AB - In cultured MRC-5 cells, ganciclovir (GCV) alone had good activity against both the established AD169 strain (IC50 8 and 9 microM) and a clinical isolate (IC50 14 microM) of human cytomegalovirus (CMV), while 3'-azido-3'-deoxythymidine (AZT) was relatively inactive [IC50 508 and > 800 (AD169 strain); > 800 microM (clinical isolate)]. When reductions in plaques were compared against reductions in the cellular metabolism of MTT at all GCV and AZT combination concentrations using an improved 3-dimensional linear regression analysis, AZT had an additive effect on the antiviral activity of GCV against the AD169 strain and potentiated the antiviral activity of GCV against the clinical isolate. Calculations showed that, in the presence of 50 microM AZT, the anti-CMV activity of GCV was unchanged for the AD169 strain, whereas the activity of GCV was increased approximately 5-10-fold for the clinical isolate. An increase in GCV efficacy for the AD169 strain first became apparent at 100 microM AZT with an approximately 3 fold increase in activity. In Swiss-Webster mice, the anti-CMV activity of GCV against murine CMV was unaffected when administered in combination with AZT. GCV given alone subcutaneously had an ED50 of 6 mg/kg which was unaffected by daily intraperitoneal doses of 320 mg/kg AZT. These results suggest that AZT will not adversely affect the efficacy of GCV against CMV in HIV-positive, non-neutropenic patients. PMID- 8215301 TI - Inhibition of the infectivity of influenza virus by tea polyphenols. AB - (-)Epigallocatechin gallate (EGCg) and theaflavin digallate (TF3) (1-10 microM) inhibited the infectivity of both influenza A virus and influenza B virus in Madin-Darby canine kidney (MDCK) cells in vitro. Study by electron microscope revealed that EGCg and TF3 (1 mM) agglutinated influenza viruses as well as did antibody, and that they prevented the viruses from adsorbing to MDCK cells. EGCg and TF3 more weakly inhibited adsorption of the viruses to MDCK cells. EGCg and TF3 (1-16 microM) also inhibited haemagglutination by influenza viruses. These findings suggest that tea polyphenols bind to the haemagglutinin of influenza virus, inhibit its adsorption to MDCK cells, and thus block its infectivity. PMID- 8215303 TI - In vitro activity of a Combretum micranthum extract against herpes simplex virus types 1 and 2. AB - The authors demonstrate in vitro antiviral activity of a methanolic extract of Combretum micranthum leaves against HSV-1 and HSV-2. This activity is present only in the extract dissolved 7 days before the assay, but not in the freshly prepared extract, thus indicating the presence of inactive precursors which undergo spontaneous transformations into active compounds. The alkaline autooxidation of the methanolic extract promotes this rapid transformation. The precursors have been identified as condensed catechinic tannins, which, under alkaline conditions, suffer rapid cleavage, intramolecular rearrangement to catechinic acid and autooxidation. The alkaline autooxidation products of the methanolic extract of C. micranthum and those of the synthetic catechinic acid show similar I.R. and U.V. absorption curves, as well as similar anti-HSV-1 and HSV-2 activities. EC50s of catechinic acid autooxidation products against HSV-1 and HSV-2 replication were 2 micrograms/ml and 4 micrograms/ml, respectively, when cell cultures were treated with the compound during virus infection. PMID- 8215304 TI - Effects of tumor necrosis factor-alpha treatment on mortality in murine cytomegalovirus-infected mice. AB - The effects of treatment with recombinant DNA-derived Tumor Necrosis Factor-alpha (TNF-alpha) in a murine model of cytomegalovirus infection were investigated. Treatment of 3-week-old Swiss Webster mice with murine TNF-alpha prior to infection with murine cytomegalovirus (MCMV) had no demonstrable effect on mortality. However, if mice were treated prior to infection with a combination of murine IFN-gamma and murine TNF-alpha, the dose of IFN-gamma required to achieve significant reduction in mortality was reduced by a factor > 10. In contrast to the beneficial effects of prophylactic TNF-alpha treatment in combination with IFN-gamma, TNF-alpha treatment of mice after MCMV infection resulted in increased mortality. The increased mortality occurred when nonlethal doses of TNF-alpha were used and required virus replication. The effects of TNF-alpha treatment on mortality in MCMV-infected mice were not predicted from cell culture experiments which evaluated the effects of TNF-alpha treatment on MCMV replication in primary mouse embryo fibroblasts. PMID- 8215305 TI - Comparative anti-influenza virus activity of 2'-deoxy-2'-fluororibosides in vitro. AB - The anti-influenza virus activity of 2'-deoxy-2'-fluoroguanosine was determined in cell culture and in explants of human respiratory epithelium by yield reduction assay. The concentration causing at least 1.0 log10 reduction in influenza A (H3N2) virus yield (EC90) at 24 h was 2.5 micrograms/ml in primary rhesus monkey kidney and 12 micrograms/ml in Madin-Darby canine kidney (MDCK) cells, compared to 0.5 micrograms/ml and 0.9 micrograms/ml, respectively, for ribavirin. The estimated therapeutic ratios for both compounds were low (< 5 to 25) in these cell types. In contrast, the EC90 values at 48 h for influenza A and influenza B virus were < or = 0.1 micrograms/ml in human respiratory epithelial explants, and concentrations up to 100 micrograms/ml did not inhibit explant outgrowth. Ribavirin was approximately 50-fold less active in this system and inhibited outgrowth at 10 micrograms/ml. 2'-deoxy-2'-fluoroguanosine was also approx. 45-fold more potent than the corresponding adenosine and inosine compounds in explant cultures. Partially resistant variants, with approximate 5 fold increases in EC50 values, could be selected by serial influenza A virus passage in MDCK cells in the presence of 2'-deoxy-2'-fluoroguanosine, which indicated that its antiviral activity is at least partially virus specific. The exceptional activity of 2'-deoxy-2'-fluoroguanosine in human respiratory epithelial cells against both influenza A and B viruses makes this compound an interesting candidate for further investigation. PMID- 8215306 TI - We need to question health care's sacred cows, fatted calves. PMID- 8215307 TI - The effectiveness of preoperative skin preparations. An integrative review of the literature. PMID- 8215308 TI - Clean vs sterile surgical skin preparation kits. Cost, safety, effectiveness. PMID- 8215309 TI - Implementation of the AORN skin shaving standard. Evaluation of a planned change. PMID- 8215310 TI - Care of the patient undergoing spinal surgery. Perioperative considerations. AB - Surgical procedures on the spine have become increasingly complex and require careful preparation and astute assessment of the patient. When the details of good patient care are attended to by a knowledgeable and well-coordinated surgical team, spinal surgery should have a successful outcome. PMID- 8215311 TI - A comprehensive guide to the halo brace. Application, care, patient teaching. AB - In several studies of different aspects of halo brace patient care, patients say they were taught very little about what to expect and how to adapt. Mangum's experience was similar. Teaching was sporadic and centered around pin-site care. There is so much more that can be done to teach and support the patient with a halo brace as he or she undergoes a difficult and challenging experience. Access to accurate information and the ability to recognize patient needs are keys to successful patient care. PMID- 8215312 TI - Sterile defibrillator test probe checks circuits, cords. PMID- 8215313 TI - Are do-not-resuscitate, do-not-intubate orders appropriate for trauma patients? PMID- 8215314 TI - Nonsteroidal anti-inflammatory drugs. PMID- 8215315 TI - The differences between clinical practice guidelines, recommended practices. PMID- 8215316 TI - Proving causation, damages in malpractice cases. PMID- 8215317 TI - New federal program encourages health professionals to report drug, device problems. PMID- 8215318 TI - Proposed recommended practices. Reducing radiological exposure in the practice setting. Association of Operating Room Nurses, Inc. PMID- 8215319 TI - Our front-line leaders deserve more than ibuprofen, junk food. PMID- 8215320 TI - Research study misleading. PMID- 8215321 TI - Gun control editorial illogical. PMID- 8215322 TI - Changes in health care result in new definitions. PMID- 8215323 TI - Fire drill in the operating room. Role playing as a learning tool. PMID- 8215324 TI - Local area network. Preparing for installation in the operating room. PMID- 8215325 TI - Documenting local anesthesia patient care. Developing the tool. PMID- 8215326 TI - Self-awareness, self-renewal, self-management. Learning to deal effectively with stress. PMID- 8215327 TI - Total knee arthroplasty. Indications, preparation, procedure. PMID- 8215328 TI - Radical gastrectomy. The role of the RN first assistant. PMID- 8215329 TI - Protecting patients, personnel, instruments in the OR. AB - The AORN "Recommended practices for care of instruments, scopes, and powered surgical instruments" should be followed: Decontamination of instruments should occur immediately after completion of the surgical procedure. Following initial decontamination by manual or automatic decontamination, instruments should be processed in an ultrasonic cleaner. Nurses should review the equipment available for decontamination and ask themselves the following questions. Are instruments being cleaned thoroughly? Does the decontamination system clean the item in a timely manner? Is precleaning of instruments necessary? Does the system save time? Is there an adequate area for decontamination? If the answers to any of these questions are debatable, nurses should reevaluate their present decontamination system. Regarding sterilization, nurses should ask the following questions. Are instruments routinely flash sterilized? Does the current procedure follow the Centers for Disease Control and Prevention recommendations for sterilizing instruments that will invade the body and enter sterile areas? Are instruments being damaged? Does the current method of sterilization offer quick turn-around time? Proper instrument processing is part of an effective infection control program. It is an important way to protect your patients from harm. PMID- 8215330 TI - Rumor vs facts in health care reform. Interview by Kathleen Hastings. PMID- 8215331 TI - Recommended practices. Environmental responsibility in the practice setting. Association of Operating Room Nurses. PMID- 8215332 TI - The American Nurses Association approves, AORN endorses more policy statements on HIV-related issues. PMID- 8215333 TI - Required technology breakthroughs to assume widely accepted biosensors. AB - Silicon microsensors have been very successful over the last decade in a wide variety of applications. Although commercialization of silicon-based biosensors has been slow, careful applications of microfabrication technologies to the development of biosensors will drive the formation of many new markets. The most promising high-volume, emerging markets include clinical analysis, health care, and environmental. For example, the worldwide sales of clinical sensors are expected to reach several hundreds of millions by 2000, whereas the total worldwide market for biosensors is forecast to reach $1 billion by the year 2000. In this article, an overview of current and potential markets is presented with an emphasis on technological barriers to overcome before biosensors will become more widely accepted. We start by explaining the relative success of physical sensors compared to biosensors. Subsequently, we review several biosensor approaches and techniques and their associated problems. Finally, the markets that these sensors are meant to serve are analyzed. PMID- 8215334 TI - Micromachined detectors for an enzyme-based FIA. AB - Micromachining techniques were applied to construct biosensor systems. The micromachined biosensors have small size, low production cost, and good reproducibility. We made some detection units for flow injection analysis (FIA). An electrochemical flow cell was fabricated, and both the enzyme immobilized column and electrochemical detector were integrated onto the same chip. A chemiluminescence detector was also fabricated and applied to the determination of glucose and lactic acid contained in human serum and urine. PMID- 8215335 TI - Fluorescent optical sensors. AB - Optical sensors are prepared by immobilizing an indicating layer on the distal end of a fiber optic cable. Dyes, enzymes, and antibodies can all be incorporated into the layer using a variety of immobilization techniques. Much of the present work is devoted to developing novel indicating schemes by combining appropriate recognition schemes into polymeric matrices. PMID- 8215337 TI - Mediated microbiosensors. PMID- 8215336 TI - A method for the assay of hydrolytic enzymes using dynamic light scattering. AB - Dynamic light-scattering techniques have been successfully used for the assay of several hydrolytic enzymes. The enzymes were assayed using substrate-coated colloidal particles. Hydrolysis of the substrate coat causes destabilization of the particles followed by particle aggregation. The rate of particle aggregation can be related to the initial concentration of added enzyme. PMID- 8215338 TI - Microfabrication and microsensors. AB - In order to fabricate microsensors, a micromachining, microfabrication technique based on LSI technologies has been used. In this paper, useful micromachining techniques are described. Examples of integrated microsensors, such as a pressure sensor including a readout circuit and a multisensor cell for blood gas analysis, are introduced. Microflow control devices, such as microvalve and a micropump for integrated chemical analysis systems, are also described. PMID- 8215339 TI - Miniaturized detectors for a chemical analysis system. AB - Recently, several studies about miniaturized chemical analysis systems fabricated with micromachining methods were reported. These systems have some advantages, such as fast response, small amount of sample, and low consumption of reagents, as compared with the conventional system. With such a small system, design of the detector units is very important to monitor analytical performance. This paper introduces some examples of micromachined detectors for miniaturized chemical analysis systems. PMID- 8215340 TI - Potentiometric response of lipid modified ISFET. AB - The gate surface of an ion-sensitive field effect transistor (ISFET) was modified with Langmuir-Blodgett (LB) film composed of fatty acid or crown ether amphiphiles to examine their potentiometric response to H+ and K+ ions. The results demonstrate the possible use of the lipid films for preparing ISFET ion sensors. PMID- 8215341 TI - Enzyme modification of LB membrane-deposited ISFET. PMID- 8215342 TI - Noninvasive blood glucose concentration monitoring method with suction effusion fluid by ISFET biosensor. PMID- 8215343 TI - Highly sensitive immunosensor with a surface photovoltage technique. PMID- 8215344 TI - New MOS-type glucose sensor using sputtered LaF3 film. PMID- 8215345 TI - Biosensors based on polymer networks formed by gamma irradiation crosslinking. AB - Water-soluble polymers immobilized by gamma irradiation have been investigated as a means of developing electrochemical sensors. Enzyme-based sensors for glucose and lactate have been made by immobilizing glucose oxidase and lactate oxidase, respectively, on platinized graphite electrodes. The enzyme is entrapped in a polymeric network of poly(vinyl alcohol) that is formed by gamma radiation crosslinking. Electrodes coated with poly (N-vinylpyrrolidone) and its corresponding monomer and then crosslinked with gamma radiation show an extraction of catecholamines into the polymer film that enhances the analytical signal for their detection by electrochemical oxidation. Poly(dimethyldiallylammonium chloride) spin-coated on a screen-printed electrochemical cell provides sufficient ionic conductivity for the cell to function as a gas sensor for oxygen, which is detected by reduction at a platinum working electrode. PMID- 8215346 TI - Applications of microfabrication techniques in electrochemical sensor development. AB - Electrochemical sensors have been used either as a whole or as an integral part of a chemical and biological sensing device. Microfabrication technology has been used in the development of electrochemical sensors. The recent advancement of micromachining techniques adds new impetus to electrochemical sensor development. Most noticeable is the application of anisotropic chemical etching, plasma etching, sacrificial layer methods, and high aspect ratio X-ray lithography to enhance the opportunity to produce scientifically and commercially viable electrochemical sensors. Examples will be used to illustrate the potential of microfabrication and micromachining techniques in electrochemical sensor development. PMID- 8215347 TI - Bacitracin production by a new strain of Bacillus subtilis. Extraction, purification, and characterization. AB - A new strain of Bacillus subtilis C 126 was isolated from sugar cane fermentation and produced an antibiotic that inhibited the growth of Micrococcus flavus. The production of the antibiotic in culture medium followed to extraction with n butanol, thin layer chromatography, and microbiological tests indicated that a polypeptide antibiotic was produced. The fraction obtained by Sephadex G-25 column and analyzed by HPLC indicated that bacitracin complex was produced. PMID- 8215348 TI - An inexpensive optical probe for measuring the local specific interfacial area. AB - An in situ optical probe was developed to measure reliably the local specific interfacial area of the suspended phase (specifically air bubbles) in a bioreactor. The light transmission-based probe can be simply and inexpensively constructed from readily available components. The probe's performance was tested in a suspension of opaque monodisperse polystyrene spheres as well as in the presence of nonspherical, nonuniformly distributed bubbles. The probe signal is directly related to the local specific interfacial area by a calibration equation obtained with polystyrene beads, as opposed to the cumbersome direct photographic bubble measurements that the probe attempts to replace. Its utility was demonstrated by measuring the specific bubble interfacial area at two locations in a bioreactor at various agitation intensities. PMID- 8215349 TI - Electroporation technique of DNA transfection. PMID- 8215350 TI - Purification and properties of Clostridium thermocellum endoglucanase 5 produced in Escherichia coli. AB - Endoglucanase 5 (EG5) has been isolated from the strain of E. coli TG1 harboring recombinant plasmid pCU108, which contains the cel5 gene of C. thermocellum. The enzyme has been produced with 98-fold purification and a final yield of 27% by using subsequent twofold high performance ion-exchange chromatography on Mono Q and high performance chromatofocusing on Mono P. The protein has a mol mass of 35 kDa and includes 3 multiple forms with pI 4.4-4.8 as evidenced by analytical gel isoelectrofocusing. EG5 cleaves CMC (Km = 0.097 g/L, Vmax = 8.2 mg/min.mg of protein), amorphous cellulose, xylan, lichenan as a substrate with an optimum temperature of 80 degrees C and pH 6.0 and Avicel (Km = 18.2 g/L, Vmax = 0.035 mg/min.mg of protein) with an optimum temperature of 60 degrees C and pH 6.0. Cellobiose in concentrations up to 200 micrograms/mL do not inhibit the hydrolysis of CMC by EG5, but 10-30 micrograms/mL of glucose significantly decrease the activity of this enzyme. The stimulating role of calcium chloride and concentration of protein in the system has been demonstrated for Avicel hydrolysis by EG5. PMID- 8215351 TI - Detection of hepatitis A virus in Mercenaria mercenaria by coupled reverse transcription and polymerase chain reaction. AB - Hepatitis A virus (HAV) is a major cause of infectious hepatitis in humans. In this respect, bivalve mollusks pose a major health concern because they are filter feeders and can concentrate the virus up to 900-fold from contaminated water. Detection of HAV has been hampered because wild-type HAV grows poorly if at all in cell culture. Here we describe a technique for the detection of HAV in shellfish based on reverse transcription coupled with the polymerase chain reaction. RNA is isolated from hard-shell clam tissue and reverse transcribed with avian myeloblastosis virus reverse transcriptase. A portion of the cDNA pool is then amplified with primers specific for HAV. In experiments with an in vitro synthesized HAV transcript, we were able to detect HAV sequence in the presence of a 200-million-fold excess of shellfish RNA. When intact virus was added to shellfish tissue before the isolation of RNA, the method was capable of detecting 10 viral RNA molecules in a reaction mixture. PMID- 8215352 TI - Phenotypic characterization of copper-resistant mutants of Methylosinus trichosporium OB3b. AB - Cultures of Methylosinus trichosporium OB3b grown in the presence of very low concentrations of copper synthesize a soluble methane monooxygenase (sMMO) that efficiently catalyzes the oxidation of trichloroethylene and other organic pollutants. Recently, we isolated five M. trichosporium OB3b mutants that express sMMO activity when grown in the presence of elevated copper concentrations (P.A. Phelps, S. K. Agarwal, G. E. Speitel, Jr., and G. Georgiou, Appl. Environ. Microbiol. 58:3701-3708, 1992). Here we show that, in contrast to the results for the wild-type cells, the addition of copper to mutant cultures grown on methane and nitrate as the nitrogen source has no noticeable effect on the growth rate and sMMO expression. In vitro experiments indicated that the copper-resistant phenotype does not arise from an increased stability of sMMO to copper deactivation. Furthermore, the mutant cultures exhibit altered speciation of copper in the extracellular fluid and have substantially decreased levels of cell associated copper. On the basis of these results, we propose that the mutant phenotype arises from defects in copper uptake and metabolism rather than from changes in sMMO expression or enzyme stability. PMID- 8215353 TI - Variation in chlorobenzoate catabolism by Pseudomonas putida P111 as a consequence of genetic alterations. AB - Pseudomonas putida P111 is able to utilize a broad range of monochlorinated, dichlorinated, and trichlorinated benzoates. The involvement of two separate dioxygenases was noted from data on plasmid profiles and DNA hybridization. The benzoate dioxygenase, which converts 3-chlorobenzoate (3-CB), 4-CB, and benzoate to the corresponding catechols via reduction of a dihydrodiol, was shown to be chromosomally coded. The chlorobenzoate-1,2-dioxygenase that converts ortho chlorobenzoates to the corresponding catechols without the need of a functional dioldehydrogenase was shown to be encoded on plasmid pPB111 (75 kb). Cured strains were unable to utilize ortho-chlorobenzoates for growth. DNA hybridization data indicated that catabolism of the corresponding chlorocatechols was coded on chromosomal genes. Maintenance of plasmid pPB111 was dependent on the presence of ortho-chlorobenzoates in the growth media. A unique variant of P111 (P111D), able to grow on 3,5-dichlorobenzoate (3,5-DCB), was obtained by continuous subculturing from media containing progressively lower and higher concentrations of 3-CB and 3,5-DCB, respectively. The low frequency of segregants able to grow on 2,5-DCB, 2,3-DCB, and 2,3, 5-trichlorobenzoate was evident by lag periods greater than 200 h. Continued subculture on 3,5-DCB resulted in the formation of new plasmid pPH111 (120 kb), which was homologous to pPB111. A probe from the clc operon, which encodes for the chlorocatechol pathway, hybridized to plasmid pPH111 and to the chromosome of the wild-type strain P111 but not to its plasmid pPB111 nor to the chromosome of strain P111A, which had lost the ability to utilize chlorobenzoates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215354 TI - A simple RNA probe system for analysis of Listeria monocytogenes polymerase chain reaction products. AB - The synthesis of an RNA probe specific for the hlyA gene of Listeria monocytogenes by in vitro transcription from a polymerase chain reaction (PCR) generated template incorporating bacteriophage T7 promoter sequences is described. This simple method produced a high yield of RNA which hybridized specifically with hlyA PCR products on a membrane, resulting in RNA-DNA hybrids which were detected by an immunoenzymatic assay with an anti-RNA-DNA hybrid antibody. The RNA probe hybridization system was more sensitive in the analysis of the PCR products than was the conventional agarose gel electrophoresis method. When applied to the analysis of PCR samples from cultures of various Listeria and non-Listeria organisms, the RNA probe was reactive in the assay of 62 different L. monocytogenes isolates but not other Listeria species. Among the non-Listeria organisms tested, only Enterococcus faecalis gave a weak positive reaction with more than 10(9) cells per ml. This reactivity disappeared at lower cell densities. This strategy for the synthesis and application of RNA probes should facilitate the analysis of PCR products in the detection of L. monocytogenes and possibly other food pathogens. PMID- 8215355 TI - Construction of a recombinant wine yeast strain expressing beta-(1,4) endoglucanase and its use in microvinification processes. AB - A genetic transformation system for an industrial wine yeast strain is presented here. The system is based on the acquisition of cycloheximide resistance and is a direct adaptation of a previously published procedure for brewing yeasts (L. Del Pozo, D. Abarca, M. G. Claros, and A. Jimenez, Curr. Genet. 19:353-358, 1991). Transformants arose at an optimal frequency of 0.5 transformant per microgram of DNA, are stable in the absence of selective pressure, and produce wine in the same way as the untransformed industrial strain. By using this transformation protocol, a filamentous fungal beta-(1,4)-endoglucanase gene has been expressed in an industrial wine yeast under the control of the yeast actin gene promoter. Endoglucanolytic wine yeast secretes the fungal enzyme to the must, producing a wine with an increased fruity aroma. PMID- 8215356 TI - Isolation, characterization, and sequence analysis of cryptic plasmids from Acinetobacter calcoaceticus and their use in the construction of Escherichia coli shuttle plasmids. AB - Three cryptic plasmids have been discovered in Acinetobacter calcoaceticus BD413. These three plasmids, designated pWM10 (7.4 kb), pWM11 (2.4 kb), and pWM12 (2.2 kb), exhibited extensive homology to one another, as shown by Southern blot hybridization and restriction site analysis data, and also hybridized with three plasmids having slightly different sizes detected in a second strain, A. calcoaceticus BD4. Plasmid pWM11 and a fragment of pWM10 were each subcloned into pUC19, yielding plasmids pWM4 and pWM6, respectively, and were used in a series of inter- and intraspecies transformation experiments. Both plasmids replicated as high-copy-number plasmids in A. calcoaceticus BD413, as well as in strains of Escherichia coli. However, when transformed into the oil-degrading strain Acinetobacter lwoffii RAG-1, both plasmids were maintained at low copy numbers. No modification of the plasmids was detected after repeated transfers between hosts. An analysis of a series of deletions demonstrated that (i) a 185-bp fragment of pWM11 was sufficient to permit replication of the shuttle plasmid in A. calcoaceticus BD413, (ii) the efficiency of transformation of A. calcoaceticus BD413 decreased according to the size of the deletion in the insert by up to 4 orders of magnitude, and (iii) the entire insert was required for transformation and replication in A. lwoffii RAG-1. The sequence of pWM11 contained several small (150- to 300-bp) open reading frames, none of which exhibited any homology to known DNA or protein sequences. In addition, a number of inverted and direct repeats, as well as six copies of the consensus sequence AAAAAAATA previously described for a cryptic plasmid from A. lwoffii (M. Hunger, R. Schmucker, V. Kishan, and W. Hillen, Gene 87:45-51, 1990), were detected. Cloning and expression of the alcohol dehydrogenase regulon from A. lwoffii RAG-1 were accomplished by using the Acinetobacter shuttle plasmid. PMID- 8215357 TI - Application of multilocus enzyme electrophoresis in studies of the epidemiology of Listeria monocytogenes in Denmark. AB - A total of 245 strains of Listeria monocytogenes were investigated. These strains were isolated from human and animal cases of listeriosis as well as from different kinds of raw and processed foods. Thirty-three electrophoretic types (ETs) were identified among the 245 strains. The strains investigated included all human clinical strains isolated in Denmark during 1989 and 1990. Seventy three percent of the strains isolated in this period were assigned to one of only two ETs (ET 1 and ET 4). ET 1, which was found to be the most frequently occurring ET among strains isolated from human clinical cases, was also found to occur rather frequently in animal clinical cases. ET 1 was, however, found only sporadically among strains isolated from foods and food factories. The data indicate that there might be something distinctive about the physiology or ecology of the ET 1 clone which makes it more likely to bring about disease in human beings either because of high pathogenicity or because of a special ability to multiply to infectious doses in processed foods. Another type, designated ET 4, was found to be the next most frequently occurring ET, after ET 1, among human clinical isolates. This could be explained by the fact that ET 4 was found to be the most frequently occurring ET within food isolates. PMID- 8215358 TI - Glucose toxicity in Prevotella ruminicola: methylglyoxal accumulation and its effect on membrane physiology. AB - When the ruminal bacterium prevotella ruminicola B(1)4-M was grown in a defined medium with an excess of glucose (3.6 mM ammonia and 50 mM glucose), the cells accumulated large amounts of cellular polysaccharide and the viable cell number decreased at least 1,000-fold. This decrease in viability was correlated with an accumulation of methylglyoxal in the supernatant (3 to 4 mM). Other genetically distinct strains of P. ruminicola produced methylglyoxal, but methylglyoxal production was not ubiquitous among the strains. When P. ruminicola B(1)4-M was grown in continuous culture (dilution rate, 0.1 h-1) with an excess of glucose, there was an oscillating pattern of growth and cell death which was correlated with the accumulation and washout of methylglyoxal from the culture vessel. Mutants which resisted an excess of glucose took up glucose at a slower rate and produced less methylglyoxal than the wild type. These mutants were, however, not stable. There was always a long lag time, and the mutants could only be maintained with a daily transfer schedule. When the mutants were transferred less frequently, methylglyoxal eventually accumulated and the cultures died. The mutants transported glucose at a threefold-slower rate than the wild type, and in each case the carrier had more than one binding site for glucose. Because glucose transport could not be driven by phosphoenolpyruvate or ATP, the glucose carrier of P. ruminicola is probably a proton symport system. When P. ruminicola B(1)4-M cultures were treated with 4 mM methylglyoxal, the delta psi decreased even though intracellular ATP concentrations were high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215359 TI - Mechanism of adsorption of hard and soft metal ions to Saccharomyces cerevisiae and influence of hard and soft anions. AB - The applicability of the hard-and-soft principle of acids and bases in predicting metal adsorption characteristics in a biological context was investigated for metabolism-independent uptake of the metal ions Sr2+, Mn2+, Zn2+, Cu2+, Cd2+, and Tl+ by Saccharomyces cerevisiae. Metal adsorption increased with external metal concentration (5 to 50 microM), although some saturation of uptake of the harder ions examined, Sr2+, Mn2+, and Zn2+, was evident at the higher metal concentrations. Cation displacement experiments indicated that, with the exception of Tl+, relative covalent bonding (H+ displacement) of the metals was greater at low metal concentrations, while weaker electrostatic interactions (Mg2+ plus Ca2+ displacement) became increasingly important at higher concentrations. These results were correlated with curved Scatchard and reciprocal Langmuir plots of metal uptake data. Saturation of covalent binding sites was most marked for the hard metals, and consequently, although no relationship between metal hardness and ionic/covalent bonding ratios was evident at 10 microM metal, at 50 microM the ratio was generally higher for harder metals. Increasing inhibition of metal uptake at increasing external anion concentrations was partially attributed to the formation of metal-anion complexes. Inhibitory effects of the hard anion SO42(-) were most marked for uptake of the hard metals Sr2+ and Mn2+, whereas greater relative effects on adsorption of the softer cations Cu2+ and Cd2+ were correlated with complexation by the soft anion S2O32(-). Inhibition of uptake of the borderline metal Zn2+ by SO42(-) and that by S2O32(-) were approximately equal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215360 TI - Cloning and nucleotide sequence of a gene from Lactobacillus sake Lb706 necessary for sakacin A production and immunity. AB - Sakacin A is an antilisterial bacteriocin produced by Lactobacillus sake Lb706. In order to identify genes involved in sakacin A production and immunity, the plasmid fraction of L. sake Lb706 was shotgun cloned directly into a sakacin A nonproducing and -sensitive variant, L. sake Lb706-B, by using the broad-host range vector pVS2. Two clones that produced sakacin A and were immune to the bacteriocin were obtained. A DNA fragment of approximately 1.8 kb, derived from a 60-kb plasmid of strain Lb706 and present in the inserts of both clones, was necessary for restoration of sakacin A production and immunity in strain Lb706-B. The sequence of the 1.8-kb fragment from one of the clones was determined. It contained one large open reading frame, designated sakB, potentially encoding a protein of 430 amino acid residues. Hybridization and nucleotide sequence analyses revealed that the cloned sakB complemented a mutated copy of sakB present in strain Lb706-B. The sakB gene mapped 1.6 kb from the previously cloned structural gene for sakacin A (sakA) on the 60-kb plasmid. The putative SakB protein shared 22% amino acid sequence identity (51% similarity if conservative changes are considered) to AgrB, the deduced amino acid sequence of the Staphylococcus aureus gene agrB. The polycistronic agr (accessory gene regulator) locus is involved in the regulation of exoprotein synthesis in S. aureus. Similar to the AgrB protein, SakB had some features in common with a family of transmembrane histidine protein kinases, involved in various adaptive response systems of bacteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215361 TI - Trypsin-dependent production of an antibacterial substance by a human Peptostreptococcus strain in gnotobiotic rats and in vitro. AB - An antibacterial substance appeared within 1 day in feces of gnotobiotic rats harboring a human intestinal Peptostreptococcus strain. It disappeared when the rat bile-pancreatic duct was ligatured or when the rats ingested a trypsin inhibitor. Anaerobic cultures of the Peptostreptococcus strain in a medium supplemented with trypsin also exhibited an antibacterial activity, which was also inhibited by the trypsin inhibitor. In vitro the antibacterial substance from both feces and culture medium was active against several gram-positive bacteria, including other Peptostreptococcus spp., potentially pathogenic Clostridium spp. such as C. perfringens, C. difficile, C. butyricum, C. septicum, and C. sordellii, Eubacterium spp., Bifidobacterium spp., and Bacillus spp. Whatever the order of inoculation of the strains, a sensitive strain of C. perfringens was eliminated within 1 day from the intestine of rats monoassociated with the Peptostreptococcus strain. These findings demonstrate for the first time that very potent antibacterial substances can be produced through a mechanism involving intestinal bacteria and exocrine pancreatic secretions. PMID- 8215362 TI - Methods to investigate the expression of lignin peroxidase genes by the white rot fungus Phanerochaete chrysosporium. AB - Two methods allowing the analysis of expression of specific lignin peroxidase (LPO) genes from white rot fungi are presented. In the first method, degenerate oligonucleotide primers derived from amino acid sequence motifs held in common among all members of the LPO gene family are used to prime the polymerase chain reaction (PCR) amplification of LPO-related nucleotide sequences from cDNA prepared by using RNA from ligninolytic cultures. The PCR products are cloned and analyzed by restriction cleavage and DNA sequencing. This method was applied to the analysis of transcripts from carbon-limited cultures of Phanerochaete chrysosporium BKM-F-1767, revealing two major classes of PCR products. One class showed DNA sequences with a high degree of similarity to the previously described CLG4 cDNA sequence (H. A. De Boer, Y. Zhang, C. Collins, and C. A. Reddy, Gene 60:93-102, 1987), whereas the other harbored DNA sequences with similarities to the L18 cDNA sequence previously described for P. chrysosporium OGC101 (T. G. Ritch, Jr., V. J. Nipper, L. Akileswaran, A. J. Smith, D. G. Pribnow, and M. H. Gold, Gene 107:119-126, 1991). The second method is based on nuclease protection assays involving isoenzyme-specific RNA probes. By using this method, the L18 related gene of P. chrysosporium BKM-F-1767 was found to be expressed under conditions of carbon and of nitrogen limitation, although the transcript levels were found to be higher in carbon-limited cultures. Furthermore, it was found that omission of veratryl alcohol addition to the culture did not affect the levels of the L18-related transcripts in carbon-limited cultures. PMID- 8215363 TI - Lignin and veratryl alcohol are not inducers of the ligninolytic system of Phanerochaete chrysosporium. AB - Phanerochaete chrysosporium is a white rot fungus which secretes a family of lignin-degrading enzymes under nutrient limitation. In this work, we investigated the roles of veratryl alcohol and lignin in the ligninolytic system of P. chrysosporium BKM-F-1767 cultures grown under nitrogen-limited conditions. Cultures supplemented with 0.4 to 2 mM veratryl alcohol showed increased lignin peroxidase activity. Addition of veratryl alcohol had no effect on Mn-dependent peroxidase activity and inhibited glyoxal oxidase activity. Azure-casein analysis of acidic proteases in the extracellular fluid showed that protease activity decreased during the early stages of secondary metabolism while lignin peroxidase activity was at its peak, suggesting that proteolysis was not involved in the regulation of lignin peroxidase activity during early secondary metabolism. In cultures supplemented with lignin or veratryl alcohol, no induction of mRNA coding for lignin peroxidase H2 or H8 was observed. Veratryl alcohol protected lignin peroxidase isozymes H2 and H8 from inactivation by H2O2. We conclude that veratryl alcohol acts as a stabilizer of lignin peroxidase activity and not as an inducer of lignin peroxidase synthesis. PMID- 8215364 TI - Biological inactivation of adhering Listeria monocytogenes by listeriaphages and a quaternary ammonium compound. AB - The use of listeriaphages as a means of disinfecting contaminated stainless-steel and polypropylene surfaces was investigated. Surfaces artificially contaminated with L. monocytogenes 10401 and 8427 were sanitized with suspensions of listeriaphages (H387, H387-A, and 2671), all belonging to the Siphoviridae family. Phage suspensions at concentrations of up to 3.5 x 10(8) PFU/ml were at least as efficient as a 20 ppm solution of a quaternary ammonium compound (QUATAL) in reducing L. monocytogenes populations. A synergistic activity was observed when two or more phages were used in combination and when phages were suspended in QUATAL. The biological activity of the three phages was not affected by QUATAL concentrations of 50 ppm and a contact time of 4 h. PMID- 8215365 TI - Cloning and sequence analysis of the meso-diaminopimelate decarboxylase gene from Bacillus methanolicus MGA3 and comparison to other decarboxylase genes. AB - The lysA gene of Bacillus methanolicus MGA3 was cloned by complementation of an auxotrophic Escherichia coli lysA22 mutant with a genomic library of B. methanolicus MGA3 chromosomal DNA. Subcloning localized the B. methanolicus MGA3 lysA gene into a 2.3-kb SmaI-SstI fragment. Sequence analysis of the 2.3-kb fragment indicated an open reading frame encoding a protein of 48,223 Da, which was similar to the meso-diaminopimelate (DAP) decarboxylase amino acid sequences of Bacillus subtilis (62%) and Corynebacterium glutamicum (40%). Amino acid sequence analysis indicated several regions of conservation among bacterial DAP decarboxylases, eukaryotic ornithine decarboxylases, and arginine decarboxylases, suggesting a common structural arrangement for positioning of substrate and the cofactor pyridoxal 5'-phosphate. The B. methanolicus MGA3 DAP decarboxylase was shown to be a dimer (M(r) 86,000) with a subunit molecular mass of approximately 50,000 Da. This decarboxylase is inhibited by lysine (Ki = 0.93 mM) with a Km of 0.8 mM for DAP. The inhibition pattern suggests that the activity of this enzyme in lysine-overproducing strains of B. methanolicus MGA3 may limit lysine synthesis. PMID- 8215366 TI - Detection of pathogenic Yersinia enterocolitica in foods and water by immunomagnetic separation, nested polymerase chain reactions, and colorimetric detection of amplified DNA. AB - A two-step polymerase chain reaction (PCR) procedure with two nested pairs of primers specific for the yadA gene of Yersinia enterocolitica was developed. The PCR assay identified all common pathogenic serogroups (O:3, O:5,27, O:8, O:9, O:13, and O:21) from three continents and differentiated pathogenic Y. enterocolitica from Y. pseudotuberculosis and from a variety of nonpathogenic yersiniae representing 25 serogroups and four species. The performance of the method was evaluated with seeded food and water samples. We compared two procedures for sample preparation prior to PCR: one was based on immunomagnetic separation of the target bacteria from the sample, using magnetic particles coated with immunoglobulin antibodies to Y. enterocolitica serogroup O:3, and the other method consisted of a series of centrifugation steps combined with proteinase treatment. Regardless of the method used, the PCR assay was capable of detecting 10 to 30 CFU/g of meat in 10(6)-fold excess of indigenous bacteria. When the samples were enriched overnight in a nonselective medium, the sensitivity was increased to approximately 2 CFU/g, except for samples with an extremely high background flora (> 10(7) CFU/g). We compared gel electrophoretic detection of PCR products with a colorimetric detection method designated DIANA (detection of immobilized amplified nucleic acids), which enabled easy visualization of amplified fragments in a microtiter plate format with an optical density reader. DIANA and gel electrophoresis showed complete concordance in their discrimination between positive and negative samples. The combination of immunomagnetic separation, nested PCR, and DIANA makes possible the development of a fully automated analytic process which requires a minimum of laboratory manipulations. PMID- 8215367 TI - F-specific RNA bacteriophages are adequate model organisms for enteric viruses in fresh water. AB - Culturable enteroviruses were detected by applying concentration techniques and by inoculating the concentrates on the BGM cell line. Samples were obtained from a wide variety of environments, including raw sewage, secondary effluent, coagulated effluent, chlorinated and UV-irradiated effluents, river water, coagulated river water, and lake water. The virus concentrations varied widely between 0.001 and 570/liter. The same cell line also supported growth of reoviruses, which were abundant in winter (up to 95% of the viruses detected) and scarce in summer (less than 15%). The concentrations of three groups of model organisms in relation to virus concentrations were also studied. The concentrations of bacteria (thermotolerant coliforms and fecal streptococci) were significantly correlated with virus concentrations in river water and coagulated secondary effluent, but were relatively low in disinfected effluents and relatively high in surface water open to nonhuman fecal pollution. The concentrations of F-specific RNA bacteriophages (FRNA phages) were highly correlated with virus concentrations in all environments studied except raw and biologically treated sewage. Numerical relationships were consistent over the whole range of environments; the regression equations for FRNA phages on viruses in river water and lake water were statistically equivalent. These relationships support the possibility that enteric virus concentrations can be predicted from FRNA phage data. PMID- 8215368 TI - NADP(+)-dependent D-threonine dehydrogenase from Pseudomonas cruciviae IFO 12047. AB - NADP(+)-dependent D-threonine dehydrogenase (EC 1.1.1.-), which catalyzes the oxidation of the 3-hydroxyl group of D-threonine, was purified to homogeneity from a crude extract of Pseudomonas cruciviae IFO 12047. The enzyme had a molecular mass of about 60,000 Da and consisted of two identical subunits. In addition to D-threonine, D-threo-3-phenylserine, D-threo-3-thienylserine, and D threo-3-hydroxynorvaline were also substrates. However, the other isomers of threonine and 3-phenylserine were inert. The enzyme showed maximal activity at pH 10.5 for the oxidation of D-threonine. The enzyme required NADP+. NAD+ showed only slight activity. The enzyme was not inhibited by EDTA, o-phenanthroline, alpha,alpha'-dipyridyl, HgCl2, or p-chloromercuribenzoate but was inhibited by tartronate, malonate, pyruvate, and DL-2-hydroxybutyrate. The inhibition by these organic acids was competitive against D-threonine. Initial-velocity and product inhibition studies suggested that the oxidation proceeded through a sequential ordered Bi Bi mechanism. The Michaelis constants for D-threonine and NADP+ were 13 and 0.12 mM, respectively. PMID- 8215369 TI - Nitrogen limitation and nitrogen fixation during alkane biodegradation in a sandy soil. AB - We investigated nutrient limitations during hydrocarbon degradation in a sandy soil and found that fixed nitrogen was initially a limiting nutrient but that N limitation could sometimes be overcome by N2 fixation. Hydrocarbon biodegradation was examined in an unsaturated sandy soil incubated aerobically at 20 degrees C with propane or butane and various added nutrients. Propane and butane degradation proceeded similarly during the first 3 months of incubation. That is, bacteria in soil amended with N oxidized these hydrocarbons more rapidly than in controls without nutrient additions or in soil with added phosphate or trace minerals. Both propane- and butane-amended soil apparently became N limited after the initial available inorganic N was utilized, as indicated by a decrease in the rates of hydrocarbon degradation. After 3 months, propane and butane degradation proceeded differently. Bacteria in propane-degrading soil apparently remained N limited because propane degradation rates stayed low unless more N was added. In contrast, bacteria in butane-degrading soil appeared to overcome their N limitation because butane degradation rates later increased regardless of whether more N was added. Analyses of total N and acetylene reduction assays supported this apparent surplus of N in butane-amended soil. Total N was significantly (P < 0.01) higher in soil incubated with butane and no N amendments than in soil incubated with propane, even when the latter was amended with N. Acetylene reduction occurred only in butane-amended soil. These results indicate that N2 fixation occurred in butane-amended soil but not in propane-amended soil. PMID- 8215370 TI - A highly purified enrichment culture couples the reductive dechlorination of tetrachloroethene to growth. AB - A microscopically pure enrichment culture of a gram-negative anaerobic bacterium, in the present article referred to as PER-K23, was isolated from an anaerobic packed-bed column in which tetrachloroethene (PCE) was reductively transformed to ethane via trichloroethene (TCE), cis-1,2-dichloroethene (cis-1,2-DCE), chloroethene, and ethene. PER-K23 catalyzes the dechlorination of PCE via TCE to cis-1,2-DCE and couples this reductive dechlorination to growth. H2 and formate were the only electron donors that supported growth with PCE or TCE as an electron acceptor. The culture did not grow in the absence of PCE or TCE. Neither O2, NO3-, NO2-, SO4(2-), SO3(2-), S2O3(2-), S, nor CO2 could replace PCE or TCE as an electron acceptor with H2 as an electron donor. Also, organic electron acceptors such as acetoin, acetol, dimethyl sulfoxide, fumarate, and trimethylamine N-oxide and chlorinated ethanes, DCEs, and chloroethene were not utilized. PER-K23 was not able to grow fermentatively on any of the organic compounds tested. Transferring the culture to a rich medium revealed that a contaminant was still present. Dechlorination was optimal between pH 6.8 and 7.6 and a temperature of 25 to 35 degrees C. H2 consumption was paralleled by chloride production, PCE degradation, cis-1,2-DCE formation, and growth of PER K23. Electron balances showed that all electrons derived from H2 or formate consumption were recovered in dechlorination products and biomass. Exponential growth could be achieved only in gently shaken cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215371 TI - Recombinational inactivation of the gene encoding nitrate reductase in Aspergillus parasiticus. AB - Functional disruption of the gene encoding nitrate reductase (niaD) in Aspergillus parasiticus was conducted by two strategies, one-step gene replacement and the integrative disruption. Plasmid pPN-1, in which an internal DNA fragment of the niaD gene was replaced by a functional gene encoding orotidine monophosphate decarboxylase (pyrG), was constructed. Plasmid pPN-1 was introduced in linear form into A. parasiticus CS10 (ver-1 wh-1 pyrG) by transformation. Approximately 25% of the uridine prototrophic transformants (pyrG+) were chlorate resistant (Chlr), demonstrating their inability to utilize nitrate as a sole nitrogen source. The genetic block in nitrate utilization was confirmed to occur in the niaD gene by the absence of growth of the A. parasiticus CS10 transformants on medium containing nitrate as the sole nitrogen source and the ability to grow on several alternative nitrogen sources. Southern hybridization analysis of Chlr transformants demonstrated that the resident niaD locus was replaced by the nonfunctional allele in pPN-1. To generate an integrative disruption vector (pSKPYRG), an internal fragment of the niaD gene was subcloned into a plasmid containing the pyrG gene as a selectable marker. Circular pSKPYRG was transformed into A. parasiticus CS10. Chlr pyrG+ transformants were screened for nitrate utilization and by Southern hybridization analysis. Integrative disruption of the genomic niaD gene occurred in less than 2% of the transformants. Three gene replacement disruption transformants and two integrative disruption transformants were tested for mitotic stability after growth under nonselective conditions. All five transformants were found to stably retain the Chlr phenotype after growth on nonselective medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215372 TI - Detection of the genes encoding botulinum neurotoxin types A to E by the polymerase chain reaction. AB - The polymerase chain reaction (PCR) was used as the basis for the development of highly sensitive and specific diagnostic tests for organisms harboring botulinum neurotoxin type A through E genes. Synthetic DNA primers were selected from nucleic acid sequence data for Clostridium botulinum neurotoxins. Individual components of the PCR for each serotype (serotypes A through E) were adjusted for optimal amplification of the target fragment. Each PCR assay was tested with organisms expressing each of the botulinum neurotoxin types (types A through G), Clostridium tetani, genetically related nontoxigenic organisms, and unrelated strains. Each assay was specific for the intended target. The PCR reliably identified multiple strains having the same neurotoxin type. The sensitivity of the test was determined with different concentrations of genomic DNA from strains producing each toxin type. As little as 10 fg of DNA (approximately three clostridial cells) was detected. C. botulinum neurotoxin types A, B, and E, which are most commonly associated with human botulism, could be amplified from crude DNA extracts, from vegetative cells, and from spore preparations. This suggests that there is great potential for the PCR in the identification and detection of botulinum neurotoxin-producing strains. PMID- 8215373 TI - Effect of water and nitrogen additions on free-living nitrogen fixer populations in desert grass root zones. AB - In this study we measured changes in population levels of free-living N2-fixing bacteria in the root zones of potted Bouteloua eriopoda and Sporobolus flexuosus plants as well as the photosynthetic indices of the plants in response to added nitrogen, added water, and added water plus nitrogen treatments. In addition, N2 fixer population changes in response to added carbon source and nitrogen were measured in plant-free soil columns. There were significant increases in the numbers of N2 fixers associated with both plant species in the water and the water plus nitrogen treatments. Both treatments increased the photosynthetic index, suggesting that plant exudates were driving N2 fixer population changes. Population increases were greatest in the water plus nitrogen treatments, indicating that added nitrogen was synergistic with added water and suggesting that nitrogen addition spared bacteria the metabolic cost of N2 fixation, allowing greater reproduction. Plant-free column studies demonstrated a synergistic carbon-nitrogen effect when carbon levels were limiting (low malate addition) but not when carbon was abundant (high malate), further supporting this hypothesis. The results of this study indicate the presence of N2 fixer populations which interact with plants and which may play a role in the nitrogen balance of desert grasslands. PMID- 8215374 TI - DNA sequences and expression in Streptomyces lividans of an exoglucanase gene and an endoglucanase gene from Thermomonospora fusca. AB - Two genes encoding cellulases E1 and E4 from Thermomonospora fusca have been cloned in Escherichia coli, and their DNA sequences have been determined. Both genes were introduced into Streptomyces lividans, and the enzymes were purified from the culture supernatants of transformants. E1 and E4 were expressed 18- and 4-fold higher, respectively, in S. lividans than in E. coli. Thin-layer chromatography of digestion products showed that E1 digests cellotriose, cellotetraose, and cellopentaose to cellobiose and a trace of glucose. E4 is poor at degrading cellotriose and cleaves cellopentaose to cellotetraose and glucose or cellotriose and cellobiose. It readily cleaves cellotetraose to cellobiose. E1 shows 59% identity to Cellulomonas fumi CenC in a 689-amino-acid overlap, and E4 shows 80% identity to the N terminus of C. fimi CenB in a 441-amino-acid overlap; all of these proteins are members of cellulase family E. Alignment of the amino acid sequences of Clostridium thermocellum celD, E1, E4, and four other members of family E demonstrates a clear relationship between their catalytic domains, although there is as little as 25% identity between some of them. Residues in celD that have been identified by site-directed mutagenesis and chemical modification to be important for catalytic activity are conserved in all seven proteins. The catalytic domains of E1 and E4 are not similar to those of T. fusca E2 or E5, but all four enzymes share similar cellulose-binding domains and have the same 14-bp inverted repeat upstream of their initiation codons. This sequence has been identified previously as the binding site for a protein that regulates induction. PMID- 8215375 TI - Metabolism of the plant toxins nitropropionic acid and nitropropanol by ruminal microorganisms. AB - The nitro toxins 3-nitro-1-propionic acid (NPA) and 3-nitro-1-propanol (NPOH), which are found in many leguminous plants, are known to be detoxified by ruminal microorganisms. The rates of the detoxification reactions are critical to acquisition of tolerance to the plants by ruminant animals, but further information is needed about factors which influence reaction rates and about the nature of the detoxification reactions. We found that rates of disappearance of NPA and NPOH varied somewhat between samples of ruminal fluid but were usually about 0.4 and 0.1 mumol/ml of ruminal fluid per h, respectively, and that rates with threefold-concentrated cells from rumen fluid were correspondingly higher. We present evidence that ruminal microbes from both cattle and sheep reduce these nitro groups in situ, so that NPA is converted to bet-alanine and NPOH is converted to 3-amino-1-propanol. These products were identified by thin-layer chromatography and, as their dabsyl derivatives, separated by high-performance liquid chromatography. The product beta-alanine was itself metabolized by these mixed suspensions of rumen microbes, so its recovery was always less than what would be estimated from NPA loss, but as much as 87% of the NPOH lost from incubation mixtures was recovered as 3-amino-1-propanol. Addition of sulfide and ferrous ions to suspensions of ruminal microbes increased the rate of NPOH reduction about threefold, but rates of NPA reduction were not similarly increased. When incubations were under hydrogen gas instead of carbon dioxide, the addition of sulfide and ferrous ions led to even greater (five- to eightfold) increases in the rates of NPOH metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215376 TI - Production of L-dihydroxyphenylalanine in Escherichia coli with the tyrosine phenol-lyase gene cloned from Erwinia herbicola. AB - The gene (tutA) encoding tyrosine phenol-lyase from Erwinia herbicola was cloned into Escherichia coli, and fusions to the lac and tac promoters were constructed. The enzyme was expressed at high levels in E. coli in the presence of isopropyl beta-D-thiogalactopyranoside or lactose as an inducer. L-Dihydroxyphenylalanine was synthesized in high yield from catechol, pyruvate, and ammonia by induced cells. PMID- 8215377 TI - Purification and characterization of a cell wall peptidase from Lactococcus lactis subsp. cremoris IMN-C12. AB - A peptidase from the cell wall fraction of Lactococcus lactis subsp. cremoris IMN C12 has been purified to homogeneity by hydrophobic interaction chromatography, two steps of anion-exchange chromatography, and gel filtration. The molecular mass of the purified enzyme was estimated to be 72 kDa by gel filtration and 23 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme has a pI of 4.0, and it has the following N-terminal sequence from the 2nd to the 17th amino acid residues: -Arg-Leu-Arg-Arg-Leu-?-Val-Pro-Gly-Glu-Ileu-Val-Glu-Glu Leu-Leu. The peptidase is most active at pH 5.8 and at 33 degrees C with trileucine as the substrate. Reducing agents such as dithiothreitol, beta mercaptoethanol, and cysteine strongly stimulated enzyme activity, while p chloromercuribenzoate had an inhibitory effect. Also, metal chelators lowered the peptidase activity, which could not be restored with Ca2+ and Mg2+. The divalent cations Cu2+, Zn2+, Fe2+, and Hg2+ completely inhibited peptidase activity. The peptidase is capable of hydrolyzing tripeptides and some dipeptides, with a preference for peptides containing leucine and with the highest activity towards the tripeptides Leu-Leu-Leu, Leu-Trp-Leu, and Ala-Leu-Leu, which were hydrolyzed with Kms of 0.37, 0.18, and 0.61 mM, respectively. PMID- 8215378 TI - Bioluminescent sensors for detection of bioavailable Hg(II) in the environment. AB - Biosensors for the detection of pollutants in the environment can complement analytical methods by distinguishing bioavailable from inert, unavailable forms of contaminants. By using fusions of the well-understood Tn21 mercury resistance operon (mer) with promoterless luxCDABE from Vibrio fischeri, we have constructed and tested three biosensors for Hg(II). Bioluminescence specified by pRB28, carrying merRo/pT, by pOS14, mediating active transport of Hg(II), and by pOS15, containing an intact mer operon, was measured in rich and minimal media. The highest sensitivities were achieved in minimal medium and were 1, 0.5, and 25 nM Hg(II) for pRB28, pOS14, and pOS15, respectively. The utility of the biosensors in natural waters was demonstrated with freshwater, rain, and estuarine samples supplemented with Hg(II). mer-lux carried by pRB28 and pOS14 responded to Hg(II) in mercury-contaminated water samples collected from a freshwater pond. Semiquantitative analyses based on light emission in samples collected from the inlet (analytically determined total mercury, approximately 20 nM) and outlet (total mercury, approximately 7 nM) of the pond showed bioavailable mercury at approximately 20 and 1 to 2 nM, respectively. Thus, the biosensors described here semiquantitatively detect bioavailable inorganic mercury (at a nanomolar to micromolar concentration range) in contaminated waters. PMID- 8215379 TI - Energetics and kinetics of maltose transport in Saccharomyces cerevisiae: a continuous culture study. AB - In Saccharomyces cerevisiae, maltose is transported by a proton symport mechanism, whereas glucose transport occurs via facilitated diffusion. The energy requirement for maltose transport was evaluated with a metabolic model based on an experimental value of YATP for growth on glucose and an ATP requirement for maltose transport of 1 mol.mol-1. The predictions of the model were verified experimentally with anaerobic, sugar-limited chemostat cultures growing on a range of maltose-glucose mixtures at a fixed dilution rate of 0.1 h-1. The biomass yield (grams of cells.gram of sugar-1) decreased linearly with increasing amounts of maltose in the mixture. The yield was 25% lower during growth on maltose than during that on glucose, in agreement with the model predictions. During sugar-limited growth, the residual concentrations of maltose and glucose in the culture increased in proportion to their relative concentrations in the medium feed. From the residual maltose concentration, the in situ rates of maltose consumption by cultures, and the Km of the maltose carrier for maltose, it was calculated that the amount of this carrier was proportional to the in situ maltose consumption rate. This was also found for the amount of intracellular maltose. These two maltose-specific enzymes therefore exert high control over the maltose flux in S. cerevisiae in anaerobic, sugar-limited, steady-state cultures. PMID- 8215380 TI - Development of a random amplification of polymorphic DNA typing method for Listeria monocytogenes. AB - The 10-mer primer OPM-01 (5'-GTT GGT GGC T-3') was used to generate random amplification of polymorphic DNA (RAPD) profiles by polymerase chain reaction for 91 strains of Listeria monocytogenes from raw milk, food, and veterinary, medical, and food-environmental sources. The profiles obtained contained 1 to 10 bands within the molecular size range of 0.5 to 5.0 kbp. Reproducibility was enhanced by annealing at low stringency and introducing a 1-min ramp time between annealing and extension temperatures. Thirty-three RAPD profiles were observed, with specific profiles being observed for strains from each source. RAPD profiles allowed discrimination within serogroups, although five RAPD profiles which were not confined to one serotype were found. Within food strains, one RAPD profile was more common than others, suggesting this to be a common type among strains from this source. PMID- 8215381 TI - Effects of temperature shift on acid and heat tolerance in Salmonella enteritidis phage type 4. AB - The transfer of cells of Salmonella enteritidis phage type 4 from 20 to 37-46 degrees C resulted in marked increases in acid and heat tolerance. The former was maximized within 5 to 15 min of the shift and was largely independent of protein synthesis. In contrast, induction of increased heat tolerance was slower, requiring more than 60 min to be completed, and was prevented by inhibition of protein synthesis. When cells were transferred to medium at temperatures between 47 and 50 degrees C, the kinetics of induction of heat tolerance were essentially the same as at the lower temperatures. In contrast, the cells became more acid sensitive. The results of these studies clearly show that although both acid and heat resistance can be enhanced by preexposure to high incubation temperatures, the mechanisms involved are different. PMID- 8215382 TI - Gene cloning, sequencing, and biochemical characterization of endoxylanase from Thermoanaerobacterium saccharolyticum B6A-RI. AB - The gene encoding endoxylanase (xynA) from Thermoanaerobacterium saccharolyticum B6A-RI was cloned and expressed in Escherichia coli. A putative 33-amino-acid signal peptide, which corresponded to the N-terminal amino acids, was encoded by xynA. An open reading frame of 3,471 bp, corresponding to 1,157 amino acid residues, was found, giving the xynA gene product a molecular mass of 130 kDa. xynA from T. saccharolyticum B6A-RI had strong similarity to genes from family F beta-glycanases. The temperature and pH optimum for the activity of the cloned endoxylanase were 70 degrees C and 5.5, respectively. The cloned endoxylanase A was stable at 75 degrees C for 60 min and displayed a specific activity of 227.4 U/mg of protein on oat spelt xylan. The cloned xylanase was an endo-acting enzyme. PMID- 8215383 TI - Comparison and genomic sizing of Escherichia coli O157:H7 isolates by pulsed field gel electrophoresis. AB - Genomic DNAs of Escherichia coli O157:H7 strains isolated from patients and food samples were analyzed by pulsed-field gel electrophoresis. The rare-cutting endonucleases SfiI and XbaI generated 6 and 10 distinct genomic profiles, respectively, for the 22 strains analyzed, indicating that this technique may find application for epidemiologic studies. Summation of XbaI fragments from five E. coli O157:H7 strains estimated the genomic length at ca. 4.7 Mb. PMID- 8215384 TI - Evaluation of radioactive and nonradioactive gene probes and cell culture for detection of poliovirus in water samples. AB - Five nonradioactive probe assays were evaluated by using chemiluminescent and colormetric signals, along with two isotopic assays and cell culture, for the detection of poliovirus in concentrated water samples. In environmental samples, a 100% correlation existed between digoxigenin and single-stranded [32P]RNA probes. All probe assays detected more positive samples than the cell culture did. PMID- 8215385 TI - Breakdown of N-terminally modified peptides and an isopeptide by rumen microorganisms. AB - Treatment of Trypticase peptides with acetic anhydride, succinic anhydride, or maleic anhydride inhibited their breakdown to ammonia by rumen microorganisms by an average of 89% after 12 h of incubation in vitro. All three treatments gave similar protection. Acetylation also protected dipeptides containing lysine and methionine from degradation. However, more effective protection was obtained by linking lysine and methionine as N-epsilon-methionyl lysine. PMID- 8215386 TI - Molecular cloning and sequence analysis of the crtB gene of Thermus thermophilus HB27, an extreme thermophile producing carotenoid pigments. AB - We have cloned and sequenced a 1.5-kb chromosomal fragment of Thermus thermophilus which promoted the overproduction of carotenoids in T. thermophilus. An open reading frame (ORF-A) coding for a polypeptide with 289 amino acids was responsible for carotenoid overproduction. The putative ORF-A protein showed significant homology with the amino acid sequences of crtB gene products (phytoene syntheses) of other microorganisms. The clone containing the ORF-A on a multicopy plasmid produced about three times as much carotenoid as that produced by the host strain, suggesting that the crtB gene product is a rate-limiting enzyme for carotenoid biosynthesis in T. thermophilus. PMID- 8215387 TI - Substrate induction and metabolite accumulation during anaerobic toluene utilization by the denitrifying strain T1. AB - The denitrifying strain T1 utilizes toluene anaerobically. We now report that anaerobic toluene degradation is inducible in strain T1. Fluoracetate treatment of cell suspensions inhibited both the rate of toluene metabolism and the formation of the toluene dead-end products benzylsuccinate and benzylfumarate, which is consistent with the pathway proposed by Evans et al. (Appl. Environ. Microbiol. 58:496-501, 1992). In addition, when either nitrate was limiting or fluoroacetate was added, benzoate was detected during toluene metabolism. PMID- 8215388 TI - Biosynthesis of the plant photoreceptor phytochrome. PMID- 8215389 TI - Processing and transport of the precursor of cathepsin C during its transfer into lysosomes. AB - The biosynthesis and processing of a lysosomal cysteine proteinase, cathepsin C (dipeptidylaminopeptidase I), was investigated by pulse-chase experiments in cultured rat macrophages. Cathepsin C is first synthesized as procathepsin C with a molecular mass of 55 kDa. Procathepsin C is then cleaved and modified within 1 h into mature cathepsin C with two chains of 25 and 7.8 kDa. A combination of pulse-chase experiments and the subcellular fractionation analysis showed that procathepsin C and cathepsin C are located in low-buoyant-density organelles and lysosomes, respectively. The reactivity of endoglycosidase H and N-glycanase and analysis of phosphorylation indicated that both precursor and mature cathepsin C are phosphorylated and N-glycosylated to give a high-mannose-type. The addition of 300-kDa mannose 6-phosphate receptor antiserum to the chase medium caused extensive release of procathepsin C into the medium, whereas the addition of control serum did not. The membrane association of procathepsin C was tested by successive extraction of cells pulse labeled for 75 min with hypotonic buffer, alkaline solution, and Triton X-100. Procathepsin C was totally extracted by hypotonic solution, whereas procathepsin D was a membrane-associated form requiring Triton X-100 for its extraction. Gel-filtration chromatography analysis of the pulse-labeled products revealed that the precursor product exists as an oligomeric form. It is suggested that the oligomerization of cathepsin C occurs before its entry into lysosomes. PMID- 8215390 TI - The state of the copper sites in human ceruloplasmin. AB - The state of the various, spectroscopically distinguishable copper sites (type 1, type 2, and type 3 copper) of human ceruloplasmin was investigated by electron spin resonance (ESR) spectroscopy. The ESR measurements were performed at 100 K and at X-band during the reaction of the protein with either ascorbate or with ferricyanide. A method was developed to directly measure the contribution of type 1 and type 2 copper signals to the ESR spectrum of the native protein. A signal arising from an unperturbed type 2 copper site, obtained by aerobically treating the protein with ascorbate, allowed the estimation that the number of type 2 copper centers detectable by ESR was substantially lower than unity. A fraction of type 1 copper sites was found to be in the reduced state and could be reoxidized by treatment with ferricyanide. The data obtained were consistent with the presence of three type 1 copper sites per protein molecule. Based on the experimentally determined stoichiometries, computer simulations of the ESR lineshape were carried out which confirmed the presence of three nonequivalent type 1 copper sites and of a noninteger amount of ESR-detectable type 2 copper in human ceruloplasmin. PMID- 8215391 TI - Effects of diacylglycerol on the activation and kinetics of the respiratory burst oxidase in a cell-free system from human neutrophils: evidence that diacylglycerol may regulate nucleotide uptake by a GTP-binding protein. AB - The respiratory burst oxidase from human neutrophils is a membrane-associated enzyme that catalyzes the reduction of oxygen to O2- at the expense of NADPH. The oxidase is dormant in resting neutrophils, but comes to life when the cells are exposed to certain activating agents. Activation requires GTP or a GTP analog and is associated with the transfer of cytosolic oxidase polypeptides to the plasma membrane. Treatment of resting neutrophil membranes with phospholipase C caused an eightfold rise in their diacylglycerol content, increased the sodium dodecyl sulfate-mediated transfer of cytosolic polypeptides to the membrane, and enhanced O2- production by the membranes after treatment with cytosol and sodium dodecyl sulfate. Use of phospholipase C-treated membranes in the cell-free system caused only a minor change in the Km and Vm for NADPH as compared with the same system containing untreated membranes, but caused the Km for the nonhydrolyzable GTP analog GTP gamma S to fall from 200 to 34 nM. Similar kinetic changes were observed with membranes treated with dioctanoylglycerol. These findings are consistent with the idea that the activity of a G protein can be regulated by diacylglycerol. PMID- 8215392 TI - Release of carcinoembryonic antigen from human tumor cells by phosphatidylinositol-specific phospholipase C: highly effective extraction and upregulation from LS-174T colonic adenocarcinoma cells. AB - Carcinoembryonic antigen (CEA), produced by gastrointestinal tumor cells, is anchored to cell membrane by a glycosyl-phosphatidylinositol moiety which can be cleaved with phosphatidylinositol-specific phospholipase C (PI-PLC). We studied the extraction of CEA from living human colon carcinoma (LS-174T, HT-29, COLO 205, and HRT-18) and pancreatic carcinoma (CAPAN) cells by PI-PLC from Bacillus cereus. The total CEA content of LS-174T cells, quantitated by Triton X-114 extraction followed by radioimmunoassay or by immunohistochemistry, was 3.5-fold higher than that of other cells (P < 0.001). The spontaneous release of CEA from LS-174T cells into culture medium was also higher than from other cells (P < 0.001), reaching 620 ng/10(7) cells (approximately 28% of cellular content) after 24 h. Overall, living LS-174T cells were highly susceptible to CEA extraction by PI-PLC, which was dependent on PI-PLC dose and on treatment time, leading in optimal conditions to the solubilization of 4100 ng/10(7) cells after 24 h (approximately 75% of total CEA). After 24 h treatment at the highest PI-PLC dose, cell lines remained viable and growing, and membrane CEA expression was not exhausted but only reduced as compared to untreated cells. At the same time, the amount of CEA solubilized by PI-PLC exceeded the CEA reduction in membranes, suggesting that enzyme treatment increased CEA turnover. This was particularly true for LS-174T cells which maintained 54% of the expression of untreated cells, whereas the amount of CEA extracted by PI-PLC reached 190% of this expression. Growing LS-174T cells thus constitute an effective material for producing high quantities of CEA by PI-PLC cleavage, especially since these cells probably "regenerate" because of enhanced turnover during PI-PLC action, thus allowing continuous CEA production. These experimental conditions also provide an interesting model for studying the modulation of CEA expression and release. PMID- 8215393 TI - Interaction of Ant-ATP with tubulin: evidence for ATP competition for the GTP E site on tubulin. AB - The interaction of the ribose-modified ATP analogue 3'-O-anthraniloyl adenosine 5'-triphosphate (Ant-ATP) with tubulin has been studied using steady-state fluorescence techniques. This analogue inhibits the polymerization of tubulin induced by ATP or GTP. When this analogue binds to tubulin, an increase in the fluorescence intensity of the analogue and a blue shift of about 10 nm in the emission maximum have been observed. It has been found that Ant-ATP binds to tubulin at a single binding site in the hydrophobic region with a dissociation constant of 0.5-1.0 microM. It has been possible to restore the fluorescence emission intensity of the tubulin-bound analogue to that of the free ligand with a concomitant shift in the wavelength of emission maximum to that of the free analogue by displacing the analogue with ATP or GTP. These results can be interpreted to suggest that ATP and GTP compete for the Ant-ATP binding site and that ATP binds at the GTP exchangeable site (E-site). PMID- 8215394 TI - Effects of oxygen and antioxidants on the mitochondrial Ca-retention capacity. AB - 2-Oxoglutarate-supported rat liver mitochondria were loaded with moderate amounts of calcium and submitted to O2 deprivation and reoxygenation. In the presence of acetoacetate, anaerobic energy production maintained Ca2+ retention by mitochondria during the anoxia period unless the Pi concentration of the incubation solution was raised to 4-6 mM. Acetoacetate prompted Ca2+ release from O2-deprived mitochondria at elevated Pi levels, presumably due to occurrence of a permeability transition of the inner membrane. Providing 3-hydroxybutyrate and malate, together with acetoacetate, was found to delay the permeability transition until O2 was reintroduced, i.e., O2 triggered a paradoxical release of Ca2+ from mitochondria under these conditions. Whether initiated by O2 in the presence of Pi or by Pi under aerobic conditions, Ca2+ release was initially activated and subsequently inhibited or reversed in the presence of alpha tocopherol (10-90 mumol.g protein-1). Similar effects were exerted by alpha tocopherol during Pi-induced Ca2+ release from oligomycin-treated mitochondria supported by succinate (+ rotenone). In addition, the permeability transition was delayed by retinol (3-30 mumol.g protein-1) while beta-carotene, ubiquinone, and water-soluble antioxidants, including Trolox C, were ineffective. Other observations suggest that the Ca(2+)-releasing and/or -retaining effects of alpha tocopherol and retinol may be independent from pro- and/or antioxidant activities. Effects resembling those of alpha-tocopherol were exerted by alpha tocopherol succinate, which is devoid of antioxidant activity. Our data indicate that the permeability transition of Ca(2+)-loaded liver mitochondria may be triggered by O2, in the presence of ketone bodies, and affected by lipid-soluble antioxidants through mechanisms seemingly unrelated to free-radical generation or scavenging. PMID- 8215395 TI - Conversion of chlorophyll b to chlorophyll a by isolated cucumber etioplasts. AB - Chlorophyllide b was converted to chlorophyll a when incubated with cucumber etioplasts in the presence of phytol, ATP, and MgCl2. Chlorophyll a was identified by retention time on HPLC, absorption, fluorescence, and excitation spectra. It is suggested that the interconversion of chlorophyll a and b plays a significant role in the establishment of the required chlorophyll a/b ratio during the adaptation of leaves to high and low light conditions. PMID- 8215396 TI - Purification and enzymatic characterization of the geranylgeranyl pyrophosphate synthase from Erwinia uredovora after expression in Escherichia coli. AB - Geranylgeranyl pyrophosphate (GGPP) synthase from Erwinia uredovora was overexpressed in Escherichia coli and purified to homogeneity from solubilized inclusion bodies. In this protein the first 13 N-terminal amino acids were replaced by 16 other amino acids resulting from the cloning vector pUC18. Nevertheless, the enzyme showed activity after purification which could be stimulated sixfold by appropriate activation conditions. The homogeneous enzyme was used to study substrate and product specificity as well as to determine Km values for isopentenyl pyrophosphate, dimethylallyl pyrophosphate (DMAPP), geranyl pyrophosphate (GPP), and farnesyl pyrophosphate (FPP). Reaction rates and Km values indicate that FPP and GPP are the genuine allylic substrates for GGPP synthase, but not DMAPP. Independent of the allylic substrate employed, GGPP was the only reaction product of the enzymatic reaction. PMID- 8215397 TI - Interaction of heme with amphiphilic peptides: use of hemin-CN to probe the interaction of calmodulin with its target peptides. AB - The interaction of heme with several amphiphilic peptides has been studied by absorption and fluorescence spectroscopy. The binding can be followed by the changes in the absorption spectrum of the heme group or by the decrease in the peptide tryptophan fluorescence due to energy transfer to the heme. Despite their small size, ranging from 26 residues for melittin to 14 for mastoporan, a high affinity for heme-CO and hemin-CN (Kd < 100 nM) may be observed. Spectral shifts in the absorption peaks and appreciable geminate recombination after photodissociation of CO from the complex peptide-heme-CO suggest the formation of a heme pocket, as for the natural heme proteins. APPLICATION: hemin-CN can be used as a probe for the interaction of calmodulin with these target peptides. Amphiphilic peptides such as melittin bind to calmodulin with a high (nM) affinity. While both the peptide and calcium-bound calmodulin bind heme-CO, only the peptide binds hemin-CN. These interactions permit studies of the competition between hemin-CN and calmodulin for binding to the peptide: while hemin-CN quenches the melittin tryptophan fluorescence, addition of calmodulin to the [melittin*hemin-CN] complex displaces the hemin-CN and the melittin tryptophan fluorescence is recovered. PMID- 8215398 TI - Antioxidant defenses of baker's yeast against free radicals and lipid peroxides in rat brain. AB - We examined through the electron spin resonance spectrometry/spin trapping technique the antioxidant activity of baker's yeast Saccharomyces cerevisiae which is known to have both enzymatic and nonenzymatic antioxidants. The components in baker's yeast were separated by differential filtration/centrifugation using centrifuge-type filter tubes, yielding four nonenzymatic thermostable fractions of varied molecular weights which scavenged 85-95% of 1,1-diphenyl-2-picrylhydrazyl in organic solution, of hydroxyl and superoxide radicals in aqueous solution, and of lipid carbon-centered radicals induced by equimolar mixture of ascorbic acid and Fe(II) salt in rat brain homogenate. Baker's yeast also inhibited the thiobarbituric acid-reactive substance formation in the cortex, midbrain, pons-medulla oblongata, cerebellum, hippocampus, and striatum. Partial characterization of the antioxidative defenses in baker's yeast against free radicals and lipid peroxides in the brain confirmed the presence of superoxide dismutase, catalase, peroxidase, and glutathione. PMID- 8215399 TI - Heme binding to calmodulin, troponin C, and parvalbumin, as a probe of calcium dependent conformational changes. AB - Heme-CO binds to the active (calcium-bound) form of calmodulin (CaM), but not to the inactive form. Despite a similarity in structure of another calcium-binding protein, skeletal muscle troponin C, both the affinity and the spectral red-shift of the absorption of the heme group are greatly decreased for troponin C relative to calmodulin. Parvalbumin, another calcium-binding protein, shows a twofold greater affinity for heme-CO relative to CaM. Unlike calmodulin and troponin C, the affinity of parvalbumin for heme-CO is even greater in the absence of calcium. The affinity of the tryptic and thrombic fragments of CaM for heme-CO are decreased relative to the entire calmodulin. The binding of heme-CO is specific as demonstrated by the discrimination of the calmodulin, troponin C, and parvalbumin pockets. The interaction of heme-CO with active (calcium-bound) CaM is rapid (ms) as determined by stopped flow measurements. No difference in kinetics was observed for mixing inactive (calcium free) CaM with a solution of [heme-CO plus calcium], indicating that the calcium-binding step and subsequent change in protein conformation are rapid. PMID- 8215400 TI - Prostaglandin G/H synthase isoenzyme 2 expression in fibroblasts: regulation by dexamethasone, mitogens, and oncogenes. AB - Mitogens increase prostaglandin synthesis in fibroblasts. In the present studies, transcriptional activation of the prostaglandin G/H synthase isoenzyme 2 (PGHS-2) gene is shown to be responsible for this induction. Transcription of the PGHS-2 gene maximally increased within 15 min of stimulation, and elevated cellular PGHS 2 mRNA, protein, and prostaglandin synthase activity were detected shortly thereafter. Pulse-chase experiments showed induced isoenzyme 2 is short lived, with a half-life of 22 min in chicken embryo fibroblasts. Neoplastic transformation of fibroblasts by a variety of oncogenes induced either or both PGHS-1 and PGHS-2 mRNAs in immortalized murine NIH3T3 cells. Some preference of oncogenes such as v-src to induce PGHS-2 mRNA has been previously observed. However, in this study exceptions in which v-src did not induce PGHS-2 mRNA were noted. Analysis of independent cell lines transformed by v-fes showed this oncogene induced both PGHS-1 and PGHS-2. Dexamethasone, a synthetic glucocorticoid, selectively decreased both basal and induced levels of PGHS-2 mRNA. Simultaneous addition of the steroid with mitogen reduced mitogen-induced PGHS-2 mRNA levels by 80%. However, nuclear run-on experiments failed to detect any decrease in PGHS-2 mRNA transcription. This suggested dexamethasone rapidly caused PGHS-2 mRNA destabilization. Cycloheximide blocked PGHS-2 mRNA decrease. A fibroblast cell line, RS2, was identified that contained only isoenzyme 2 and possessed PGHS activity that was more highly mitogen-inducible than in any other cell line yet described. Mitogen-inducible activity in RS2 cells was inhibited by aspirin, indicating that PGHS-2, like PGHS-1, can be inactivated by this drug. PMID- 8215401 TI - Renaturation of lysozyme--temperature dependence of renaturation rate, renaturation yield, and aggregation: identification of hydrophobic folding intermediates. AB - Renaturation of denatured-reduced hen egg white lysozyme was analyzed at temperatures between 4 and 70 degrees C using the reduced/oxidized glutathione renaturation system. With an increase in temperature to 50 degrees C both renaturation rate constant and renaturation yield increased while formation of aggregates decreased. Denatured-reduced lysozyme and early folding intermediates were less stable against heat than native lysozyme at temperatures above 60 degrees C. Renaturation at 70 degrees C resulted in no reconstitution of lysozyme activity but the highest level of aggregation. Renaturation of denatured-reduced hen egg white lysozyme was further analyzed in the presence of the hydrophobicity indicating fluorescence dye 1-anilinonaphalene-8-sulfonate at temperatures between 10 and 40 degrees C. The change in fluorescence intensity, the generation of enzyme activity, renaturation yield, and the formation of aggregates were studied. The results showed that early folding intermediates possess a strong hydrophobic nature. With an increase in temperature both the renaturation rate and the decay rate of hydrophobicity-mediated fluorescence increased. Consequently, with increasing temperature, accumulation of hydrophobic folding intermediates and formation of insoluble aggregates decreased, leading to an increase in the renaturation yield. PMID- 8215402 TI - Characterization of alpha-glucosidases from rainbow trout liver. AB - Three forms of alpha-glucosidase were separable in trout liver by DE-52 chromatography, isoelectrofocusing, and gel filtration. Two forms showed acid pH optima, hydrolyzed glycogen, maltose, and 4-methylumbelliferyl alpha-glucoside, and were associated with the lysosomes. The third enzyme form was largely associated with microsomes and was present in the highest activity; it showed a neutral pH optimum and did not hydrolyze glycogen. Molecular weights were 181 +/- 2, 130 +/- 1.5, and 365 +/- 3 kDa for the acid types I and II and the neutral enzyme, respectively. Maximal activities and kinetic and physical properties of the three enzymes were compared in liver samples from control, resting fish versus fish that underwent exhaustive swimming exercise. The properties of liver acid alpha-glucosidase type I changed significantly in response to exercise; maximal activity increased by 80% and Km values for both glycogen and maltose dropped by 50% in exercised, versus control, fish. Under the same exercise condition, liver glycogen phosphorylase a activity also increased 4.4-fold. These changes in alpha-glucosidase type I are consistent with an activation of the enzyme, in parallel with phosphorylase activation, under physiological stress conditions that promote glycogenolysis and glucose export from liver. These results are, we believe, the first demonstration of the activation of the glucosidic route of glycogenolysis in response to a physiological stress and suggest that the glucosidic route has a significant role to play in complementing the phosphorolytic pathway in the metabolic response by liver to the fuel demands of working muscle. PMID- 8215403 TI - A diffusion-controlled step in the catalytic cycle of nitrous oxide reductase from Wolinella succinogenes. AB - The viscosity test was applied to the highly active nitrous oxide reductase purified from Wolinella succinogenes to determine whether the catalytic cycle may contain a diffusion-controlled step. For this test, the benzyl viologen cation (BV+)-N2O oxidoreductase reaction, which exhibits a kcatBV/KmBV approximately 2 x 10(8) M-1 s-1 at 23 degrees C and pH 7.1, was run in solutions of nominally nondenaturing viscogens that were used to increase microviscosity. The parameters kcatN2O and kcatBV were unaffected by viscosity in the range of viscogen concentrations that were not inhibitory and where the data were well behaved. KmBV, but not KmN2O, was observed to increase linearly with relative viscosity with a slope of 0.14 for all viscogens surveyed. The results, when considered in the context of a plausible kinetic model for the BV(+)-N2O oxidoreductase reaction, suggest that one of the two one-electron reactions between BV+ and enzyme is diffusion-controlled but only partially rate determining. The ratio of the second-order-rate constants for these two one-electron steps is estimated to be about 6.1, and the larger rate constant to be about 1.1 x 10(9) M-1 s-1. There would appear to be no diffusion-controlled step associated with the half-reaction which results in reduction of N2O to N2. PMID- 8215404 TI - Dimer- and oligomerization of the erythropoietin receptor by disulfide bond formation and significance of the region near the WSXWS motif in intracellular transport. AB - The receptor for erythropoietin (EpoR), a primary regulator of erythropoiesis, belongs to the cytokine receptor family. Although the mechanisms of signal transduction through the receptors of this family are largely unknown, increasing numbers of the receptors have been shown to form a hetero- or homodimer. To address the possibility that the EpoR dimerizes, we made a truncated mutant receptor that lacks most of the cytoplasmic domain and expressed it either alone or with the wild-type receptor in an IL-3-dependent cell line, DA-3. Dimerization of the receptor was demonstrated by a coimmunoprecipitation using an antiserum against the cytoplasmic domain of the receptor. Epo stimulation did not have a detectable effect on dimerization. Coimmunoprecipitation experiments in COS-7 cells further revealed that only the extracellular domain of the receptor is required for dimerization. The "WSXWS" motif, conserved in the cytokine receptor family, was shown to not be required for dimerization. Diagonal two-dimensional gel analysis of the EpoR expressed in DA-3 transfectants showed that a substantial portion of the receptor forms dimers or oligomers with disulfide bonds. Western blot analysis, using an antiphosphotyrosine antibody, revealed that a portion of these dimers or oligomers become tyrosine phosphorylated after Epo stimulation, thus suggesting that these forms are expressed on the cell surface and activated by Epo stimulation. PMID- 8215405 TI - Cytosolic protein phosphatase may turn off activated NADPH oxidase in guinea pig neutrophils. AB - Protein phosphatase inhibitors, okadaic acid and calyculin A, potentiated and elongated N-formyl-methionyl-leucyl-phenylalanine-induced superoxide anion (O2-) production in guinea pig neutrophils. The activity of NADPH oxidase in the membrane fraction prepared from phorbol 12-myristate 13-acetate-stimulated neutrophils was inactivated by the addition of the cytosol from resting neutrophils, such inactivation of NADPH oxidase was also suppressed by the protein phosphatase inhibitors. We previously reported that phosphorylation of the 46-kDa protein by protein kinase C is one of the activation mechanisms of NADPH oxidase-dependent superoxide anion production. In the cytosol fraction, we found protein phosphatase activity that catalyzed dephosphorylation of 32P labeled phosphoproteins including the 46-kDa protein. Dephosphorylation of the 46 kDa protein was inhibited by the addition of okadaic acid and calyculin A. These results indicate that dephosphorylation of the 46-kDa protein by protein phosphatase is involved in the inactivation of NADPH oxidase. NADPH oxidase activity in guinea pig neutrophil may be regulated by the phosphorylation/dephosphorylation state of the 46-kDa protein by protein kinase C and protein phosphatase. PMID- 8215407 TI - Effects of diabetes on the activity and content of the branched-chain alpha ketoacid dehydrogenase complex in liver. AB - Severe ketotic diabetes induced in rats by streptozotocin resulted in a reduction in activity of the hepatic branched-chain alpha-ketoacid dehydrogenase complex, regardless of whether activity was expressed on the basis of liver wet weight, total liver, liver protein, or liver DNA. A decrease in enzyme specific activity (units of enzyme activity per mg of enzyme protein) was found responsible for the reduction in measurable enzyme activity of the complex. Insulin treatment reversed the decrease in enzyme specific activity. Treatment of tissue extracts with phosphoprotein phosphatase had no effect, indicating that activity of the complex was decreased by some mechanism other than reversible phosphorylation. Specific protein components of the complex were also not found reduced by the diabetic state. Induction of severe ketotic diabetes in rats previously fed a low protein diet resulted in activation of the enzyme as a consequence of dephosphorylation. Nevertheless, the specific activity of the dephosphorylated enzyme of diabetic, low-protein-fed rats was decreased relative to that of control, low-protein-fed animals. Reconstitution studies with tissue extracts fortified with the purified E1 component indicate that severe diabetes induces a defect in this component of the hepatic branched-chain alpha-ketoacid dehydrogenase complex. PMID- 8215406 TI - Amino acid sequence of a high redox potential ferredoxin (HiPIP) from the purple phototrophic bacterium Rhodopila globiformis, which has the highest known redox potential of its class. AB - Rhodopila globiformis HiPIP has a redox potential (ca. 450 mV) that is 100 mV higher than any other known iron-sulfur protein. The amino acid sequence contains 57 residues and can be aligned with that of Thiobacillus ferrooxidans without any insertions or deletions and is 51% identical. Rp. globiformis HiPIP is also similar to that of Rhodocyclus tenuis, but six- and two-residue gaps must be postulated and there is only 37% identity. Most of the amino acid residues near the iron-sulfur cluster are similar in these two species based on inspection of the three-dimensional structure of Rc. tenuis HiPIP. The reason for the higher redox potential may be a more hydrophilic environment of the Rp. globiformis HiPIP iron-sulfur cluster due to the above two deletions and to substitution of Ser 32 for Gly. Rp. globiformis is unusual in that it has a cytochrome c2 in addition to the HiPIP, and it too has a very high redox potential. These results suggest that the cytochrome c2 and HiPIP may function interchangeably and that the species normally resides in a very high potential environment, although it is not known to grow aerobically in the dark. PMID- 8215408 TI - 6-substituted 3,4-benzocoumarins: a new structural class of inducers and inhibitors of CYP1A1-dependent activity. AB - A new synthetic route was utilized to prepare 6-substituted 3,4-benzocoumarins where the substituents were iodo, fluoro, trifluoromethyl, bromo, chloro, isopropyl, ethyl, t-butyl, methyl, hydrogen, amino, phenyl, or nitro; 3,4 naphthocoumarin was also synthesized. The relative affinities of these congeners for the aryl hydrocarbon (Ah) receptor were determined using rat hepatic cytosol and 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin ([3H]TCDD) as the radioligand. In addition, the Ah receptor agonist activity of the 6-substituted 3,4 benzocoumarins was determined from their concentration-dependent induction of ethoxyresorufin O-deethylase (EROD) activity. In contrast with many other structural classes of halogenated aromatics, there was not a correlation between the structure-binding versus structure induction relationships for the 6 substituted 3,4-benzocoumarins. These results suggested that some of these congeners may exhibit partial Ah receptor antagonist activities and this was investigated by determining the inhibitory effects of 6-substituted 3,4 benzocoumarins on TCDD-induced EROD activity in rat hepatoma H4II E cells in culture. Only four compounds (6-isopropyl, 6-phenyl, 6-fluoro, and 6-t-butyl) inhibited the TCDD-induced response (21.7 to 64.4% inhibition) and the mechanism of action of the most active inhibitor, 6-t-butyl-3,4-benzocoumarin, was further investigated. In contrast, with other partial Ah receptor antagonists such as alpha-naphthoflavone, cotreatment of rat hepatoma H4II E cells with 1 nM TCDD plus 1 and 10 microM 6-t-butyl-3,4-benzocoumarin did not result in decreased levels of the Ah receptor complex (liganded with TCDD). In addition, there was not significant inhibition of TCDD-induced CYP1A1 mRNA levels or protein as determined by Northern and Western blot analyses. The results suggest that 6-t butyl-3,4-benzocoumarin or one of its metabolites is a post-translational inhibitor of CYP1A1-dependent enzyme (EROD) activity in this cell line and thus represents a novel Ah receptor-independent inhibition of CYP1A1. PMID- 8215409 TI - Molecular cloning, sequencing, and analysis of the cDNA for rabbit muscle glycogen debranching enzyme. AB - Six peptides were isolated from glycogen debranching enzyme purified from rabbit muscle, and their sequences were determined. A cDNA library made from rabbit muscle using random hexamer primers was screened with oligonucleotide probes constructed in accordance with these peptide sequences. Seven cDNA clones comprising the open reading frame were found, whereas oligo(dT) cDNA libraries yielded no positive clones because of the long 3'-nontranslated region of 2.3 kb. The open reading frame of 4665 bases codes for a 1555-amino-acid protein of M(r) 177,542. Compared to the sequence from human muscle, there are an additional 40 amino acid residues upstream from the N-terminus, and the next 10 residues show no homology. For the remaining 1505 residues, the two sequences exhibit an identity of 93%. The four consensus sequences commonly found at the carboxy termini of beta-strands in the alpha/beta barrel domains of amylases and glucanotransferases are also found in the N-terminal half of the debranching enzyme, suggesting that this structural domain may be present. This and other evidence suggests that the N-terminal half may encompass the transferase activity, leaving the glucosidase activity for the C-terminal half. The latter shows no significant homology to known proteins. An unusual feature of the sequence is the presence of three pairs of adjacent cysteines, which may explain inhibition of the enzyme by organic arsenites. PMID- 8215410 TI - Isolation and characterization of human liver cytochrome P450 2C19: correlation between 2C19 and S-mephenytoin 4'-hydroxylation. AB - In an effort to identify and characterize minor forms of human liver cytochrome P450, immunoblot analyses of microsome samples were developed with antibodies to various P450s that recognized multiple human P450s. Four P450s were recognized in immunoblot analyses of human liver microsome samples developed with an antibody previously demonstrated to specifically recognize rat 2B1/2. Three of these P450s were identified as 2A6, 2C9/10, and 2E1 and the fourth was termed P450UK. A monoclonal antibody to 2C9/10 recognized P450UK in addition to 2C9/10. In order to identify P450UK, it was purified and subjected to amino-terminal amino acid analysis. The amino-terminal sequence obtained for P450UK was identical to the sequence deduced from a cDNA encoding CYP2C19, thus identifying P450UK as 2C19. The relative levels of 2C19 were determined in 14 human liver microsome samples by quantitative immunoblot analyses developed with the anti-2C9/10 antibody. These analyses demonstrated that 2C19 was not detected in one sample and its levels varied 10.5-fold in the remaining samples. The levels of 2C19 were compared to the relative levels and catalytic activities of multiple human liver P450s. The levels of 2C19 and the ability of the samples to 4'-hydroxylate S mephenytoin were found to strongly correlate (r2 = 0.79). In summary, this is the first demonstration of the expression of 2C19 at the enzyme level, and the correlation studies suggest that 2C19 plays a role in the 4'-hydroxylation of S mephenytoin. PMID- 8215411 TI - Spermine inhibition of the permeability transition of isolated rat liver mitochondria: an investigation of mechanism. AB - Mitochondria that have accumulated Ca2+ can be induced to undergo a permeability transition: the inner membrane becomes nonselectively permeable to small (< 1500 Da) solutes. The molecular mechanism(s) underlying this transition, which is Ca(2+)-dependent and cyclosporin A-sensitive, has yet to be clearly elucidated. Our laboratory has recently identified the polyamine spermine as an inhibitor of the permeability transition of isolated rat heart mitochondria. In this study, we have used spermine, in combination with a series of triggering agents, to clarify several mechanistic details of the transition process in isolated rat liver mitochondria. Mitochondrial swelling was monitored as an indicator of transition occurrence. Our results indicate that: (1) spermine inhibits the permeability transition of isolated rat liver mitochondria; (2) the sensitivity of the permeability transition of liver mitochondria to spermine is highly dependent on the ionic composition of the assay medium; (3) K+ interacts with a site outside the mitochondria to decrease spermine effectiveness; (4) spermine likewise acts at an external site; and (5) the Ca2+ uniporter in its inactive form is not the protein responsible for mediating the permeability transition. PMID- 8215412 TI - Characterization of the plasmalemma ATPase from the cyanobacteria Synechococcus PCC 6311 and PCC 7942. AB - Biochemical properties of the ATPase from the plasma membrane of the cyanobacteria Synechococcus PCC 6311 and PCC 7942 were examined. ATPase activity associated with purified plasma membrane vesicles was strongly inhibited by 100 microM vanadate (87%), 100 microM diethylstilbestrol (70%) and 100 mM fluoride ions (83%). No inhibition was observed in the presence of dicyclohexylcarbodiimide, nitrate, azide, or molybdate. A 50% activation was observed in the presence of 50 mM KCl but none was observed in the presence of NaCl or NH4Cl. This ATPase was able to form a pH gradient, the amplitude of which was decreased by the presence of 100 microM vanadate. On Western blot of the plasmalemma proteins, no labeling was observed with a monoclonal antibody against the beta subunit of the F0-F1 ATPase, although staining was observed with the 55 kDa subunit of the thylakoid membrane ATPase. After phosphorylation of plasmalemma vesicles, by [gamma-32P]ATP, the autoradiograms of the electrophoreses, performed under acid conditions, exhibited labeling of a 110-kDa protein. The results indicated that the Synechococcus plasma membrane ATPase can be classified as a H+ translocating P-type ATPase and compared to the plant plasmalemma ATPase. PMID- 8215413 TI - Free radical scavenging action of baicalein. AB - TJ-960 is a Japanese Kampo (traditional herbal) medicine used for the treatment of epilepsy. It's a crude drug, an extract of nine herbs, and consists of many known and unknown components. Among the known components of TJ-960, we found that 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (baicalein) might be the most potent scavenger for radicals. In the present study, we examined in vitro the radical scavenging effect of baicalein in detail using electron spin resonance spectrometry. Furthermore, we examined in vivo its effect on the thiobarbituric acid-reactive substances (TBARS) levels and superoxide dismutase in the brain of rats with FeCl3-induced epilepsy and on hippocampal delayed neuronal death in gerbils with transient ischemia. In in vitro experiments, baicalein quenched in a dose-dependent manner 1,1-diphenyl-2-picrylhydrazyl, superoxide, and hydroxyl radicals. In the FeCl3-induced epileptic model, baicalein suppressed the increase in the TBARS level at the FeCl3-injected site. Baicalein also inhibited hippocampal neuronal death induced by 5 min of cerebral ischemia in gerbils. Hence the present study suggested that baicalein is one of the active components in TJ-960, which partially contributes to the antiepileptic and neuronal protective effects of TJ-960, and that the mechanism of its pharmacological action is based upon radical quenching and antioxidative effects. PMID- 8215414 TI - Studies on the inhibition of collagen synthesis in fibroblasts treated with paraquat. AB - Paraquat (methyl viologen) is an industrial herbicide which upon entering many cell types can be enzymatically reduced and in the presence of oxygen, subsequently generate the superoxide radical anion (O2-). This is its mode of toxicity in many of these cells. In vivo, it has been shown to preferentially accumulate in lung tissue, leading to tissue destruction and marked fibrosis. Collagen accumulation has also been noted in paraquat-treated lung slices in vitro. In studies designed to investigate these effects, it has been found, unexpectedly, that paraquat inhibits collagen synthesis in isolated fibroblasts. This inhibition is not due to overt cellular toxicity nor to inhibition of prolyl hydroxylase (directly or by cofactor depletion). While this effect could be unique to paraquat, it may be relevant to a more generalized role for free radicals in regulating collagen synthesis at the level of the individual cell. PMID- 8215415 TI - An engineered change in the L-malate sensitivity of a site-directed mutant of sorghum phosphoenolpyruvate carboxylase: the effect of sequential mutagenesis and S-carboxymethylation at position 8. AB - A recombinant, site-directed mutant form of sorghum phosphoenolpyruvate carboxylase (PEPC), in which the phosphorylatable serine residue (Ser-8) was changed to cysteine (S8C), was chemically modified by iodoacetic acid and iodoacetamide for the purpose of testing the effect of introducing a negative charge at position 8. S-Carboxymethylation of the Cys-8 enzyme by iodoacetic acid decreased its sensitivity to L-malate from an I0.5 (50% inhibition) value of 0.12 to 0.35 mM at pH 7.3 when the active-site domain was protected during modification by the substrate phosphoenolpyruvate (PEP). In contrast, neither S carboxymethylation of the wild-type enzyme nor modification of the mutant enzyme by iodoacetamide caused any change in the enzyme's sensitivity to L-malate. The modified, substrate-protected forms of the Ser-8 and S8C PEPCs had Km(total PEP) and Vmax values virtually identical to those of the unmodified control enzymes. Similar specific increases in the I0.5 value of L-malate have been reported previously for in vitro phosphorylated leaf and recombinant Ser-8 PEPCs, the site directed mutant Asp-8 enzyme, and C4-leaf PEPC purified from light-adapted sorghum or maize (in vivo phospho-form). Therefore, these data from different but complementary experimental approaches provide convincing evidence that the effect of phosphorylation of Ser-8 on the L-malate sensitivity of sorghum C4-PEPC is caused by the introduction of negative charge into this N-terminal regulatory domain. PMID- 8215416 TI - Regulation of the activity and phosphorylation of the plasma membrane Ca(2+) ATPase by protein kinase C in intact human erythrocytes. AB - Previously the plasma membrane-bound or purified Ca(2+)-translocation ATPase (Ca2+ pump) was found to be activated and phosphorylated by protein kinase C in vitro (K. K. W. Wang et al. 1991, J. Biol. Chem. 266, 9078-9085). We now show that in intact human erythrocytes phorbol-12-myristate 13-acetate (PMA), a known stimulator of protein kinase C, decreases the amplitude of the intracellular calcium ([Ca2+]i) transient induced by 2.5 microM CaCl2 and 10 microM A23187. Since PMA did not affect Ca2+ influx, the decrease in amplitude was most likely due to the stimulation of the Ca2+ pump, the major mechanism of calcium extrusion in these cells. The effect was dose-dependent, the maximum decrease in amplitude (33%) occurring at 1 microM PMA. The depression of the [Ca2+]i transient was further enhanced by the phosphatase inhibitor okadaic acid. It was reversed by the protein kinase C inhibitor staurosporine and could not be mimicked by inactive PMA analogues. In erythrocytes labeled with [32P]orthophosphate, PMA treatment phosphorylated the Ca(2+)-ATPase in a dose-dependent manner. The phosphorylation was inhibited by staurosporine and was slightly enhanced by okadaic acid. Changes in lipid phosphorylation and content were studied under the same conditions in intact cells. The turnover of 32P and lipid phosphate in phosphatidylinositol 4,5-bisphosphate (PIP2) was inhibited by 1 mM adriamycin, concomitant with an increased amplitude of the [Ca2+]i transient. The PIP2 content and its 32P radioactive did not, however, change with PMA stimulation. We conclude that while both protein kinase C and polyphosphoinositides are regulators of Ca(2+)-ATPase activity in the intact human erythrocyte, stimulation of the enzyme activity by PMA is predominantly protein kinase C-mediated. PMID- 8215417 TI - Brain hexokinase and intramitochondrial compartments of ATP: fact and artifact. PMID- 8215418 TI - Multiple attack mechanism in the porcine pancreatic alpha-amylase hydrolysis of amylose and amylopectin. AB - The action pattern of the porcine pancreatic alpha-amylase (PPA) is studied with amylose and amylopectin used as substrates. For initial stages of enzyme hydrolysis, the shape of the product chain length distribution is estimated and compared with predictions of the theory of multiple attack. The theory assumes sliding of the enzyme along the substrate polysaccharide chain without dissociation between successive cleavages. Very different initial distributions of oligomers are observed for amylose and amylopectin. In both cases, however, the theory describes the chain length distributions well. The temperature dependence of the shape of the multiple attack product distribution indicates that with rising temperature the probability of sliding increases with respect to that of dissociation. This dependence can be expected if the sliding occurs in a loose complex where enzyme and substrate are bound mainly due to hydrophobic interactions between their two continuous hydrophobic surfaces. The possible physiological role of the multiple attack in the mechanism of pancreatic amylases of mammals is discussed. The correspondence between the average length of the sliding of PPA and characteristic chain lengths of alpha-1,4-bound glucose fragments in amylopectin suggests that the degree of multiple attack of PPA is close to the optimum level required for efficient digestion of starch in the small intestine. PMID- 8215419 TI - Inhibition of actin stimulation of skeletal muscle (A1)S-1 ATPase activity by caldesmon. AB - We have previously shown that caldesmon inhibits the actin-activated ATPase activity of myosin subfragments in parallel with inhibition of myosin subfragment.ATP binding to actin (M. E. Hemric, and J. M. Chalovich, 1988, J. Biol. Chem. 263, 1878-1885; L. Velaz, R. H. Ingraham, and J. M. Chalovich, 1990, J. Biol. Chem. 265, 2929-2934). From these data, we suggested that caldesmon is a competitive inhibitor of binding of myosin subfragment-1 to actin. To confirm this result, we now show the effect of caldesmon on the steady-state parameters of ATP hydrolysis by (A1)S-1 at increasing actin concentrations. Low ionic strength conditions were used to maximize the interaction between (A1)S-1 and actin. In both the presence and absence of smooth muscle tropomyosin, caldesmon caused a twofold decrease in the kcat and more than a 12-fold change in the KATPase. Therefore, competition of binding of myosin to actin by caldesmon contributes to the reduction in ATPase activity in both the presence and the absence of tropomyosin. PMID- 8215420 TI - Cancer cachexia, malnutrition, and tissue protein turnover in experimental animals. AB - The role of malnutrition in the development of cachexia in rats bearing the Yoshida ascites hepatoma AH-130 was investigated by comparing the changes in tissue protein turnover in these animals with those observed in pair-fed controls. The tumor elicited in rats an early and conspicuous loss of body weight and tissue waste. Protein loss was particularly prominent for the gastrocnemius muscle and the heart and less pronounced for the soleus, while the diaphragm was little affected. Liver, kidneys, and spleen transiently increased in weight then regressed and eventually atrophied, while adrenals were enlarged over the whole experimental period. Protein waste was mainly due to acceleration of tissue protein breakdown, this protein hypercatabolic state being associated with increased cathepsin D activity in liver and gastrocnemius. In pair-fed animals the liver showed a marked protein loss resulting from enhanced catabolism, while the sharp decrease of heart protein content and the less prominent waste of the gastrocnemius were due to a reduction in protein synthesis. The total plasmatic concentration of free amino acids in AH-130-bearing rats was decreased at Day 4, when the tumor was actively proliferating, and returned to control values at Day 10, when the tumor had reached a stationary state. On the contrary, in pair-fed animals total plasma amino acids decreased over the whole experimental period. Plasma branched-chain amino acids were unchanged or even decreased in tumor hosts, while the Gly/Pro ratio was elevated in pair-fed rats. The intracellular concentration of free amino acids was higher in stationary than in exponentially- growing tumors, reflecting the enhanced proteolytic rates observed in stationary tumor cells. On the whole, the results suggest that reduced food uptake and metabolic competition by the tumor are not sufficient to justify the marked hypercatabolism in host tissues during the AH-130 hepatoma growth. The profound differences between tumor-bearing and pair-fed animals suggest that, if malnutrition undoubtedly played a role in this model of cancer cachexia, its effects were overwhelmed and subverted in the frame of the tumor-host interplay that dictated a distinctively peculiar syndrome. PMID- 8215421 TI - Relationship between lipid peroxidation, fatty acid composition, and ascorbic acid in the liver during carbohydrate and caloric restriction in mice. AB - Growing OF1 mice were treated on a short-term basis with ad libitum, caloric restricted, or carbohydrate-restricted diets, maintaining the same intake of vitamins and minerals in the three groups. Caloric intake was 60% of controls both in the caloric-restricted and in the carbohydrate-restricted groups. Neither global nor carbohydrate restriction changed liver superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, cytochrome oxidase, GSH, uric acid, or malondialdehyde (HPLC). Ascorbate was decreased in both restricted groups. Carbohydrate restriction, but not caloric restriction, increased unsaturation indexes of fatty acids in all lipid classes analyzed and increased sensitivity to peroxidation by one order of magnitude. It is concluded that short term caloric restriction does not seem to increase antioxidants and decrease peroxidation in the mouse liver whereas long-term restriction can avoid decreases of antioxidants and increases of peroxidation during aging. Our experiments support the prevailing view that the caloric restriction phenomenon is due to a reduction in calories themselves instead of to a reduction in carbohydrates. This last manipulation strongly increases sensitivity to peroxidative damage in the liver. The results show that in vivo fatty acid unsaturation is a main factor in determining the sensitivity to lipid peroxidation. PMID- 8215422 TI - Accumulation of the nuclear dioxin (Ah) receptor and transcriptional activation of the mouse Cyp1a-1 and Cyp1a-2 genes. AB - The treatment of C57BL/6 mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to the nuclear uptake of the arylhydrocarbon receptor (AhR) and transcriptional activation of Cyp1a-1 and Cyp1a-2 (S. T. Okino, et al., J. Biol. Chem. 267, 6991, 1992). In the present study, early nuclear uptake of the AhR and its role in transcriptional activation of the Cyp1 genes have been evaluated. After 30 min following a dose of TCDD to C57BL/6 mice, the AhR could be detected in liver nuclei. The effect of TCDD treatment within 30 min enhanced the transcriptional rate of the Cyp1a-2 gene to 70% of its maximal rate, with maximal levels of transcription occurring after 1 h. Early increases in 1a-2 mRNA were also observed by 30 min and increased to maximal levels by 12 h. In contrast, the levels of Cyp1a-1 transcription were 5 to 10% of maximal levels at 30 min, and gradually increased to maximal levels by 2 h. Concordant with the levels of transcription, 1a-1 mRNA was not detected until 1 h following TCDD treatment. While the AhR is responsible for transcriptional activation of the Cyp1a-1 gene, the concordant increase in the nuclear accumulation of the ligand-dependent AhR and Cyp1a-2 gene transcription suggests that the receptor plays an important role in the regulation of the Cyp1a-2 gene. PMID- 8215423 TI - Reductive activity of a manganese-dependent peroxidase from Phanerochaete chrysosporium. AB - A manganese-dependent peroxidase (MnP) from Phanerochaete chrysosporium catalyzed the reduction of cytochrome c in a reaction mixture containing H2O2, Mn(II) tartrate, and p-hydroquinone. Electron spin resonance studies have shown that the hydroquinone-dependent reductive activity of MnP is due to the benzosemiquinone formed upon the one-electron oxidation of p-hydroquinone by Mn(III)-tartrate, which is formed upon the oxidation of Mn(II) by MnP. The reductive activity increased linearly with an increase in the concentration of p-hydroquinone. The reductive activity was also observed using other hydroquinones such as methylhydroquinone, 2,5-dimethylhydroquinone, and trimethylhydroquinone. The apparent Km values for Mn(II) and H2O2 for the hydroquinone-dependent reductive activity were similar to those for oxidative reactions of MnP. A stoichiometry study showed that about 1.5 mol of cytochrome c was reduced per mole of H2O2 consumed. The stoichiometry decreased with an increase in the concentration of H2O2. The optimal pH for the reductive activity was 5.0, approximately the physiological pH of the fungus. The reduction of cytochrome c was also observed using a quinone and cellobiose:quinone oxidoreductase isolated from the extracellular medium of the fungus. PMID- 8215424 TI - Inhibition of spinach D-glyceraldehyde 3-phosphate: NADP+ oxidoreductase (nonphosphorylating) by adenylate compounds: the effect of dead-end inhibitors on a steady state random reaction mechanism. AB - D-Glyceraldehyde 3-phosphate: NADP+ oxidoreductase, nonphosphorylating (GNR; EC 1.2.1.9) purified from spinach leaves was investigated by initial velocity analysis. The hyperbolic saturation curves became nonhyperbolic when NADP+ was varied at elevated D-glyceraldehyde 3-phosphate (G3P) concentrations (sigmoidicity) or when G3P was varied at low NADP+ concentrations (pseudo substrate inhibition), suggesting a random bi bi mechanism (Scagliarini et al. Plant Physiol. 94, 1337-1344, 1990). Free ATP was a linear competitive inhibitor of both NADP+ with KI 0.5 +/- 0.2 mM (SD) and G3P with KI 3.2 +/- 0.2 mM as determined by data in the hyperbolic range of responses when the nonvaried substrate was saturating. Similarly ADP inhibited competitively with KI 1.9 +/- 0.4 mM (NADP+) and 3.5 +/- 0.5 mM (G3P). Inhibition was mixed-type when the nonvaried substrate was below saturation. ATP, but not ADP, tended to enhance the nonhyperbolic behavior of GNR, resulting in potentiated inhibition at high [G3P]/[NADP+] ratios. The Mg-chelated form of ATP was less effective. The rate equation of a steady state random bi bi reaction mechanism in the presence of a dead-end inhibitor was derived. Suitable values of the rate constants were chosen to fit the kinetic data for the uninhibited enzyme. These values and the measured inhibition constants inserted in the rate equation can satisfactorily account for the nonhyperbolic inhibition patterns of ATP and ADP. The generalized model represents a possible alternative to allosteric models in interpreting nonlinear kinetics and dead-end inhibition of two-substrate enzymes. PMID- 8215425 TI - Amino acid sequences of cytochromes c-551 from the halophilic purple phototrophic bacteria, Ectothiorhodospira halophila and E. halochloris. AB - The cytochromes c-551 from Ectothiorhodospira halophila and E. halochloris contain 78 and 79 residues, respectively. The sequences can be aligned without the need to postulate any internal deletions or insertions to give 63% identity. They are apparently distantly related to the class I cytochromes c, based on the location of the heme attachment site near the N-terminus and the sixth ligand methionine near the C-terminus. Alignment with cytochromes c5 from Azotobacter and Pseudomonas, with cytochromes c6 from cyanobacteria and algae, and with cytochromes c-555 from the green phototrophic bacteria suggests that residues which occupy important positions in the three-dimensional structures of these proteins have their equivalents in the Ectothiorhodospira cytochromes c-551, but the levels of overall identity are very low, around 30%. Although the Ectothiorhodospira cytochromes c-551 are apparently distantly related to the above, they should be regarded as representative of a new subclass of type I bacterial cytochromes c. Homologs of all of the cytochromes c normally found in Pseudomonas and Azotobacter have now been found in one or more purple bacterial species. Among these, cytochrome c5 homologs are the most widely occurring in purple, green, and cyanobacteria. For the first time, all families of phototrophic bacteria plus Pseudomonas can be related to one another at the molecular level. PMID- 8215426 TI - Serum and glucocorticoid regulation of gene transcription and expression of the prostaglandin H synthase-1 and prostaglandin H synthase-2 isozymes. AB - Mitogenic stimulation has been shown to increase both prostaglandin H (PGH) synthase-1 (PGHS-1) and PGH synthase-2 (PGHS-2) mRNA levels, although the time course and magnitude of induction are different for the two genes. To investigate the mechanism for mRNA induction, we conducted nuclear run-off assays of these two genes in 3T3 cells and correlated mitogen-induced changes in PGHS gene transcription with changes in PGHS mRNA and PGHS isozyme expression. We also examined the mechanism for glucocorticoid inhibition of PGHS mRNA expression and the effects of glucocorticoids on PGHS isozyme expression. Serum stimulation of quiescent 3T3 cells led to a sequential increase in PGHS-2 gene transcription, PGHS-2 mRNA, and PGHS-2 enzyme levels. PGHS-2 gene transcription increased over 25-fold within 30 min of serum addition resulting in an over 70-fold increase in PGHS-2 mRNA by 1 h, and maximal PGHS-2 enzyme expression by 2 h. Increased PGHS-2 isozyme expression thus appears to depend on transcriptional activation of the gene. Transcription of the PGHS-2 gene declined after 30 min, and PGHS-2 mRNA levels declined similarly after 1 h, leading to a return of PGHS-2 levels to near basal levels by 6 h. Glucocorticoids, which previously have been shown to inhibit mitogen-stimulated increases in PGHS-2 levels, were found to inhibit serum stimulated increases in PGHS-2 gene transcription by 70%, resulting in a 70% reduction in peak serum-stimulated PGHS-2 mRNA levels also. Western blotting with PGHS-2 specific antisera demonstrated that while dexamethasone simply reduced PGHS-2 mRNA levels, it completely suppressed expression of PGHS-2 protein. The coincidental reduction in PGHS-2 transcription, PGHS-2 mRNA, and enzyme levels by dexamethasone, provides further support for the hypothesis that control of transcription is one primary control mechanism for regulating PGHS-2 expression. That complete suppression of PGHS-2 enzyme expression occurs following partial suppression of PGHS-2 mRNA, however, suggests that other mechanisms may also contribute to the glucocorticoid effect. A small, but reproducible, increase in transcription of the PGHS-1 gene occurred 3 h following serum stimulation, coincident with a three- to fourfold increase in PGHS-1 mRNA; PGHS-1 mRNA remained elevated for at least 3 h. Dexamethasone reduced, but did not completely inhibit, the serum-stimulated increases in PGHS-1. However, changes in PGHS-1 mRNA were not accompanied by detectable changes in PGHS-1 protein in the presence or absence of dexamethasone. PMID- 8215427 TI - The concept of energy-rich phosphate compounds: water, transport ATPases, and entropic energy. PMID- 8215428 TI - Secondary substrate binding in aspartic proteinases: contributions of subsites S3 and S'2 to kcat. AB - The kinetic parameters kcat and Km were determined at 25 degrees C and pH 5.5 for endothiapepsin and rhizopuspepsin acting on the series of substrates Ac-Ala(m) Lys-Nph-Ala(n)-amide where Nph is p-nitrophenylalanine, and m and n equal 0-4. Kinetic parameters were also determined at 25 degrees C and pH 3.5 for pig pepsin acting on the series of substrates Ac-Ala(m)-Phe-Nph-Argn-Ala(n)-amide, where m equals 0 to 2 and n equals 0 or 1, and another series based on -Ile-Glu-Phe-Nph Arg-, which is the core of a series of peptides designed by Dunn et al. (1986, Biochem. J. 237, 899-906). Km values were found to be largely independent of increases in the chain length of the substrates whereas kcat values showed large increases with increasing chain length. With endothiapepsin and rhizopuspepsin the largest increases (between 13-fold and over 150-fold) were obtained when alanine residues were added in positions P3 and P'2 and thus are similar to those observed previously with penicillopepsin. Additions of alanines to positions P2, P'3, and P'4 gave much smaller increases. In the case of pig pepsin the results were not as clearcut. Whereas the largest increases were seen for positions P3 and P'2 only with some of the peptides, the increases were strongly dependent on the length of the peptides. With some of the longer peptides the increases were comparable to those seen for positions P2 and P'3. Thus, whereas the addition of two alanines in position P3 to the dipeptide Ac-Phe-Nph-amide caused a large proportional increase in kcat, the increase was much smaller when the addition was made to the homologous tetrapeptide and even smaller when made to the pentapeptide Ac-Ala-Phe-Nph-Arg-Ala-amide. Additions of arginine in position P'2 gave large increases in kcat for all three peptides of the series. PMID- 8215429 TI - A new, sensitive fluorogenic substrate for papain based on the sequence of the cystatin inhibitory site. AB - We have designed and tested a new papain substrate with intramolecularly quenched fluorescence. It is based on a highly conserved sequence in all members of the cystatin superfamily that participates in the inhibition of cysteine proteinases. This substrate, O-aminobenzoyl (Abz)-QVVAGA-ethylenediamine-2-4-dinitrophenyl (EDDnp) is very sensitive to papain with a second-order rate constant kcat/Km of 3.1 10(7) M-1S-1. It is also efficiently hydrolyzed by cathepsin L, although the kcat/Km for this proteinase is about 60-fold lower than that for papain. This change is due to a decrease in kcat, the Km's are almost identical. This allows clear functional discrimination between these two proteinases, and may lead to the development of selective inhibitors for individual cysteine proteinases. Unlike most commonly used papain substrates, Abz-QVVAGA-EDDnp is not hydrolyzed by trypsin. The papain cleavage site was identified as the A-G bond by N-terminal amino acid sequencing. The use of sensitive and specific substrates such as the one described here will prove invaluable for investigating cysteine proteinase activities in parasite infections. The close interaction between papain or cathepsin L with Abz-QVVAGA-EDDnp is compared to that with cystatin inhibitors, which all include a QxVxG consensus segment in their structure. PMID- 8215430 TI - Evidence for a glycosaminoglycan chain on a portion of articular cartilage fibronectins. AB - Fibronectin heterogeneity is, in part, the result of post-translational modifications. In these experiments, cartilage fibronectins were purified by anion exchange chromatography, followed by gelatin affinity chromatography or immunoprecipitation, and, finally, sodium dodecyl sulfate--polyacrylamide gel electrophoresis (NaDodSO4 PAGE). A substantial, although variable, portion of the fibronectins from canine and equine cartilages of all ages required salt concentrations from 0.2 to 1.0 M for elution from DEAE-cellulose. This was in contrast to plasma fibronectin which eluted with 0.1 M NaCl, but these results were consistent with observations made on human cartilage by Brown and Jones (1990 J. Rheumatol. 17, 65-72). When cartilage explants were incubated with Na2 35SO4=, the cartilage fibronectins were sulfated and the fibronectins which eluted with high salt contained from 5- to 50-fold more radiosulfate than the fibronectins which eluted with 0.1 M NaCl. A fraction of the 35SO4= which copurified with the cartilage fibronectin and comigrated with it in NaDodSO4-PAGE could be removed by digestion with chondroitinase ABC. This suggested that a percentage of cartilage fibronectins are covalently linked to a chondroitin sulfate or dermatan sulfate chain and thus might also appropriately be called proteoglycans. Alternatively, there is a proteoglycan which binds so tightly to fibronectin that separation is not achieved even in the presence of urea, sodium dodecyl sulfate, and mercaptoethanol. PMID- 8215431 TI - The influence of amino acid sequence on the fibrillogenicity and amyloidogenicity of the carboxy-terminus of beta-amyloid precursor protein. AB - C-APP, a synthetic peptide corresponding to the C-terminal 20 amino acids of beta amyloid precursor protein, forms amyloid fibrils in vitro. We investigated the effect of altering the C-APP sequence or deleting part of it on its ability to form amyloid fibrils. Substituting any single amino acid in the C-APP sequence with alanine did not prevent the formation of CAPP-like fibrils. Peptides with single or multiple substitutions that included T11, F14, F15, or Q19 showed reduced fibril-forming capacity while those with K1 and/or K13 replaced with alanine or glutamic acid showed enhanced capacity. When P10 or F14 was replaced with alanine, the fibrils were less congophilic than C-APP fibrils. All of the truncated peptides that were able to form fibrils contained at least 9 amino acids from the N-terminus of C-APP or amino acids 7-20 from the C-terminus. However, several peptides that met these criteria, but started at Q3 or contained only 2-4 amino acids C-terminal to P-10, failed to form many or typical fibrils. Peptides that contained the C-APP sequence plus 5-20 adjacent amino acids from the beta-amyloid precursor protein formed fibrils less readily than C-APP and most of the fibrils were not congophilic. The exception was CAPP-30, which formed moderate amounts of congophilic fibrils resembling C-APP fibrils morphologically. Therefore, proteolysis which releases C-APP from these peptides (except CAPP-30) would be predicted to enhance their amyloidogenicity. These results suggest that several features of C-APP peptide may be important in fibril formation. One of these features is the length of the peptide, with lengths of about 10, 20, or 30 amino acids, favoring fibril formation. PMID- 8215432 TI - Isolation of an inhibitor for the independent mannose 6-phosphate receptor endocytosis of bovine beta-glucuronidase by human fibroblasts. AB - Adsorptive endocytosis of bovine beta-glucuronidase by human fibroblasts is mediated by two different membrane receptors: one recognizes phosphomannosyl residues on the enzyme, the other is yet a undefined recognition marker (A. Gonzalez-Noriega, R. Coutino, V. M. Saavedra, and R. Barrera (1989) Arch. Biochem. Biophys. 268, 649-658). We have purified a bovine liver inhibitor for the endocytosis of the bovine beta-glucuronidase mediated by the recently proposed recognition marker. The inhibitor is partially susceptible to periodate oxidation, can be released from a peptide backbone by mild alkali treatment, can be reduced by sodium borohydride, and can be adsorbed to anionic but not to cationic resins. Although the chemical structure of the isolated marker has not been determined, results indicate a 122-Da molecule which may contain amino alcohol groups and may be found in a 1800-Da glycosidic chain. PMID- 8215433 TI - Electrical conductivity of differently treated isolated cuticular membranes by impedance spectroscopy. AB - A comparative study of the electrical properties of isolated tomato cuticles (native, Na+, and Ca2+ forms) in contact with different NaCl solutions has been performed by impedance spectroscopy measurements. In all cases, equivalent circuits consisting of a parallel combination of a constant phase element and a resistance were found, and variation with NaCl concentration of both parameters has been considered. From the electrical parameters, the cuticle conductivities and equivalent capacities were determined, and a comparison between conductivity values at C = 0 (without electrolyte contribution) and those obtained with dry membranes is also made. Differences in conductivity and capacity values for the three cuticles are explained by some changes in the structure and electrical interactions. PMID- 8215434 TI - Manganese(II) activation of 3-phosphoglycerate mutase of Bacillus megaterium: pH sensitive interconversion of active and inactive forms. AB - The effects of manganese(II) ions and of pH were studied on 3-p-glycerate mutase purified from Bacillus megaterium. Mn2+ ions converted the enzyme within a few minutes from a catalytically inactive form to one that was catalytically active even after Mn2+ had been removed. The enzyme reverted over 60-90 min to the inactive form, from which further activation-deactivation cycles could be elicited. The slow, temperature-dependent, activation, and deactivation is suggestive of change in protein conformation. No other metal ion was found that activated more than 4% as much as Mn2+. Activation by Mn2+ was strongly pH dependent in the physiological pH range, consistent with displacement of 2 H+. Together with the pH dependence of the catalytic activity itself, the system displayed pronounced pH sensitivity in the pH range 6.5-8.0. The findings suggest that pH changes, documented for forming and germinating spores of B. megaterium, can account for much of the mutase control associated with accumulation and later utilization of 3-phosphoglycerate depots. PMID- 8215435 TI - Covalent dimerization of recombinant human interferon-gamma. AB - An apparently nonreducible covalent dimer has been consistently observed as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE). These studies endeavor to understand the nature of this covalent dimerization. Amino acid sequence analysis of a recombinant human interferon gamma stored for 2 years showed a major sequence starting with the intact N terminal methionine and a minor sequence corresponding to the C-terminal seven amino acids of the intact protein. Moreover, when the same material was analyzed by gel filtration in the presence of 8 M urea, a minor peak corresponding to the dimer was observed prior to the monomer peak. Reducing and nonreducing SDS-PAGE also showed a minor band corresponding to a dimer. These results suggest that the reactions of C-terminal processing and dimerization have occurred during storage. Reverse-phase chromatography of stored, unfractionated material showed three peaks. Mass spectral analysis of the first, second, and third peaks gave molecular weights of 16,900, 16,100, and 33,000. Since no major cleavage was observed in the N-terminal region of the protein, the observed masses suggest that the first peak corresponds to residues 1 to 144 (a full-length molecule), the second peak to residues 1 to 137 (des 7 interferon-gamma), and the third peak to a dimer. Calculation of theoretical molecular weight from the amino acid sequence suggests that this dimer corresponds to some combination of the intact protein and des 7 protein. Tryptic peptide maps in conjunction with sequence and mass analyses identified a new tryptic peptide in the map of the dimer corresponding to residue 133 to 137 followed by residues 1 to 7. The conclusion is recombinant methionyl human interferon-gamma undergoes a specific cleavage at the C-terminal side of residue 137 phenylalanine, and a conventional peptide bond was formed between residues 137 and 1 methionine. PMID- 8215436 TI - Purification and characterization of a tripeptidyl peptidase I from human osteoclastomas: evidence for its role in bone resorption. AB - Tripeptidyl peptidase I (EC 3.4.14.9), which cleaves tripeptides from the N terminus of synthetic substrates, has been purified from human osteoclastomas (a bone tumor containing large numbers of normal osteoclasts). The enzyme has an M(r) of 48 kDa but forms aggregates with an M(r) of about 700 kDa. The tripeptidyl peptidase has an acidic pH optimum (approximately pH 5.0), suggesting that it has a lysosomal localization and prefers substrates with a hydrophobic amino acid in the P1 position. There is an absolute requirement for a nonsubstituted N-terminus. The enzyme is inhibited by reagents which modify serine and histidine residues. Lysosomal tripeptidyl peptidase is known to be capable of cleaving Gly-Pro-X triplets from synthetic collagen-like polypeptides. Ala-Ala-Phe-CH2Cl, a potent inhibitor of osteoclastoma tripeptidyl peptidase, inhibits osteoclastic bone resorption in an in vitro test system. This suggests that tripeptidyl peptidase I, secreted by osteoclasts, is involved at some stage in the degradation of bone collagen. PMID- 8215437 TI - Photosynthesis in Phosphoenolpyruvate carboxykinase-type C4 plants: mechanism and regulation of C4 acid decarboxylation in bundle sheath cells. AB - The mechanism and regulation of C4 acid decarboxylation in phosphoenolpyruvate (PEP) carboxykinase-type C4 plants was examined in isolated bundle sheath cell strands. These cells decarboxylated added oxaloacetate to PEP at rates exceeding 2.5 mumol min-1 mg-1 chlorophyll when ATP was added. This requirement for ATP could be replaced by malate plus ADP; under these conditions this cytosol-located decarboxylation of oxaloacetate via PEP carboxykinase was sustained by respiratory ATP. It was confirmed that respiratory ATP production was linked primarily to the oxidative decarboxylation of malate via NAD malic enzyme. This process, measured as pyruvate production, was highly dependent on Pi. Besides being required to generate ATP, Pi had a second role which was probably associated with the transport of malate into mitochondria. Maximum rates of malate decarboxylation via NAD malic enzyme substantially exceeded the minimum rates necessary for providing ATP for cytosolic oxaloacetate decarboxylation. When malate was added with oxaloacetate, ADP and Pi rates of malate decarboxylation of between 3 and 4 mumol min-1 mg-1 chlorophyll were recorded. About half of this activity was sustained by the reoxidation of NADH coupled to reduction of oxaloacetate via malate dehydrogenase. When malate was added without oxaloacetic acid, respiration by these bundle sheath cells was stoichiometrically linked with the oxidation of malate to pyruvate. This malate-dependent respiration was stimulated by adding ADP or phosphorylation uncouplers; it was not significantly inhibited by including oxaloacetate. Possible mechanisms of regulation of the partitioning of C4 acid decarboxylation between PEP carboxykinase in the cytosol and mitochondrial NAD malic enzyme are discussed. PMID- 8215438 TI - Alpha-tocopherol interacts with natural micelle-forming single-chain phospholipids stabilizing the bilayer phase. AB - The effect of the association of alpha-tocopherol (vitamin E) with single chain or very asymmetric phospholipids has been studied by 31P nuclear magnetic resonance, Fourier transform infrared spectroscopy, and light microscopy. Our results demonstrate that alpha-tocopherol stabilizes and forms bilayer structures in systems composed of either 1-palmitoyl-sn-glycero-3-phosphocholine, 1-O hexadecyl-2-acetyl-sn-glycero-3-phosphocholine, 1-O-hexadecyl-sn-glycero-3 phosphocholine, or 1,2-dipalmitoyl-sn-glycero-3- phosphocholine/1-palmitoyl-sn glycero-3-phosphocholine, whereas in the absence of alpha-tocopherol all these systems produce micellar structures. The free hydroxyl group of alpha-tocopherol is shown to be important in stabilizing the bilayer structure by comparing the effects produced by an analog of alpha-tocopherol, alpha-tocopheryl acetate, which has the hydroxyl group blocked by an acetyl group. It is suggested that the complementary shapes of alpha-tocopherol and the asymmetric phospholipids may be the reason for the stabilization of the bilayer structure. PMID- 8215439 TI - Direct photoaffinity labeling of rat liver carbamoyl phosphate synthetase I with ATP. AB - The adenine subsites of the ATP sites of rat liver carbamoyl phosphate synthetase I have been localized by direct photoaffinity labeling with ATP. The synthetase is known to utilize two molecules of ATP, apparently in mechanistically discrete steps and at separate ATP sites. UV irradiation of the synthetase in the presence of [alpha-32P]ATP resulted in the incorporation of label. Peptide analysis of the ATP-photolabeled synthetase demonstrated that the labeling was extremely selective. To localize the sites of ATP photoincorporation to discrete regions of the synthetase which appear to be structural domains, the enzyme was photolabeled with [alpha-32P]ATP and subjected to limited proteolytic digestion. Consideration of these data indicated that the internal domains B and C were preferentially labeled and that there was lesser, but significant, labeling of the N-terminal domain A. Omission of the required allosteric activator N-acetylglutamate from the photolabeling mixture resulted in an approximately 60% decrease in label incorporation and an accompanying decrease in the extent of label incorporation in domain B. Consideration of these N-acetylglutamate effects, together with previous findings on the effects of the allosteric activator, confirmed the following functional identification of the ATP sites: domain B participates in binding the molecule of ATP involved in bicarbonate activation, whereas domain C participates in binding the molecule of ATP involved in carbamate phosphorylation. PMID- 8215440 TI - Modulation of bradykinin-induced calcium signals by oxidative stress in PC12 cells. AB - The influence of oxidative stress on agonist-stimulated changes of intracellular free calcium and inositol trisphosphate in the neurosecretory PC12 cell line was investigated. The oxidant H2O2 modulated the bradykinin-induced calcium signal by decreasing the initial peak and the plateau phase in the same manner as tetraphorbolacetate, an activator of protein kinase C. Inositol trisphosphate formation, induced by bradykinin was also decreased by oxidative stress. Thiol protecting agents were able to restore the altered signal. In contrast to this, radical quenching substances had no influence on calcium signals in stressed cells. Inhibitors of several protein kinases, such as protein kinase C, protein kinase A, or cyclic GMP-dependent protein kinase showed the ability to protect the plateau phase of calcium signals against oxidative stress, but not the peak response. These results indicate that under the influence of oxidative stress multiple targets within the signal transduction cascades are affected. PMID- 8215441 TI - The mannose receptor and the cation-dependent form of mannose 6-phosphate receptor have overlapping cellular and subcellular distributions in liver. AB - The trafficking of newly synthesized lysosomal enzymes is mediated by two distinct mannose 6-phosphate receptors (MPRs). These receptors have been shown previously to have nonidentical distributions among subcellular fractions purified from bovine liver [D. J. Messner et al. (1989) J. Cell Biol. 108, 2149 2162]. In that study, a 170-kDa protein was discovered to be strikingly enriched in a subclass of bovine liver membranes containing the 46-kDa cation-dependent MPR (CD-MPR). The identity and distribution of this protein are described in the present study. The apparent size, extent of glycosylation, and amino-terminal amino acid sequence (XXTRPFLIYNED) of the 170K protein suggest it is the mannose receptor, a cell-type specific protein present at high levels in liver sinusoidal cells (but not hepatocytes). This identification was confirmed by demonstrating that the 170K protein can bind to mannose affinity columns. Antibodies specific for the 170K protein/mannose receptor were generated and purified using a synthetic peptide corresponding to its N-terminal sequence. Western blotting with the anti-170K peptide antibodies indicate the mannose receptor is highly enriched in membrane fractions immunoisolated with antibodies to the CD-MPR, but less enriched (by several-fold) in fractions obtained with antibodies specific for the 270-kDa insulin-like growth factor II/cation-independent MPR (IGF-II/CI-MPR). A differential overlap between the mannose receptor and the MPRs can also be detected by indirect immunofluorescence of bovine liver sections. These observations indicate that mannose receptor-enriched membranes of liver sinusoidal cells contain significant levels of the CD-MPR, but not the IGF-II/CI MPR. PMID- 8215442 TI - Cobalt(II) and nickel(II) ions as promoters of free radicals in vivo: detected directly using electron spin resonance spectrometry in circulating blood in rats. AB - We employed an electron spin resonance (ESR)2 spectrometer and used a direct detection technique for determining free radicals in circulating blood in rats. We found that the simultaneous intravenous injection of CoCl2 (10-500 mM) and ascorbic acid (100 mM) led to the formation of ascorbic acid free radicals. The potential of the Co(II) salt for producing ascorbic acid radicals was found to be dose-dependent, and was 10-fold stronger than that of a Fe(III) salt. Low height signals of the ascorbic acid radical were also observed during the simultaneous injection of NiCl2 (500 mM) and ascorbic acid (100 mM). This study clearly demonstrated that the metal ions of iron family are promoters of free radicals in vivo. These results also provide evidence to support the speculation based predominantly on in vitro experiments, that the mechanism responsible for the toxicity produced by excessive intake of transitional metal ions may involve the formation of free radicals. PMID- 8215443 TI - Reversal of the red beet tonoplast H(+)-ATPase by a pyrophosphate-generated proton electrochemical gradient. AB - The reversal of the tonoplast H(+)-ATPase to mediate ATP synthesis was investigated in tonoplast vesicles isolated from red beet (Beta vulgaris L.) storage tissue. Our approach involved use of the H(+)-PP(i)ase to establish a proton electrochemical gradient (delta muH+) across the tonoplast vesicle membrane to drive the H(+)-ATPase in reverse. However, an initial problem with this approach was the presence of an adenylate kinase activity in the tonoplast fraction that interfered with measurement of ATP synthesis as a coupling between the H(+)-ATPase and H(+)-PP(i)ase. Inclusion of the adenylate kinase inhibitor p1p5-di(adenosine)pentaphosphate (Ap5A) in assays at 50 microM led to a complete inhibition of this activity and allowed measurement of ATP synthesis coupled to PPi hydrolysis. When measured in the presence of Ap5A, PPi-dependent ATP synthesis was blocked by Triton X-100 and inhibited by gramicidin D, imidodiphosphate, nitrate, and bafilomycin A. These results are consistent with PPi-dependent ATP synthesis occurring as a coupled process involving a delta muH+ established across the membrane. Furthermore, the observation that ATP synthesis is inhibited by inhibitors of the tonoplast H(+)-ATPase (nitrate and bafilomycin A) would suggest that this enzyme is involved in the synthetic reaction and can operate in reverse to synthesize ATP from ADP and Pi. A thermodynamic analysis of coupling between the H(+)-PP(i)ase and H(+)-ATPase suggests that PPi-driven ATP synthesis could only occur under these reaction conditions if the H+/substrate stoichiometries for the H(+)-PP(i)ase and H(+)-ATPase were 1 and 2, respectively. These values are consistent with transport stoichiometries previously determined for these enzymes in red beet tonoplast vesicles using kinetic methods. PMID- 8215444 TI - Excess substrate inhibition of xanthine oxidase: a reexamination. AB - Xanthine oxidase has long been considered to be subject to inhibition by excess substrate. It is now shown that, although such inhibition can be seen in Tris or N,N-bis(2-hydroxyethyl)glycine buffers, earlier reports in which phosphate, pyrophosphate, or Veronal buffers were used were probably the result of a spectrophotometric artifact imposed by stray light in the incident beam. PMID- 8215445 TI - 8-Azido-adenine nucleotides as substrates of ecto-nucleotidases in chromaffin cells: inhibitory effect of photoactivation. AB - The components of the ecto-nucleotidase pathway at the extracellular surface of adrenal chromaffin cells are the enzymatic activities responsible for the hydrolysis of granular nucleotide compounds released during the secretory response. The azido-nucleotides have been largely employed to characterize nucleotide binding sites. The 8-azido-adenine nucleotides were studied as substrates of ecto-nucleotidases in cultured chromaffin cells by HPLC procedures. 8-Azido-ATP (8-N3-ATP) was a good substrate for ecto-ATPase activity, the Km value was 256.30 +/- 36.41 microM, and the Vmax value was 14.33 +/- 0.84 nmol/min x 10(6) cells. 8-Azido-ADP (8-N3-ADP) was dephosphorylated by the ecto-ADPase activity with a Km value of 595.29 +/- 67.44 microM and Vmax value of 6.86 +/- 0.45 nmol/min x 10(6) cells. These kinetic parameters were similar to those obtained with ATP and ADP in the same culture and incubation conditions. 8-Azido AMP (8-N3-AMP) was not hydrolyzed by the ecto-5'-nucleotidase activity. The 8 azido-nucleotides competitively inhibited the hydrolysis of adenine nucleotides, with Ki values in the same range as the Km. After uv photoactivation, the three 8 azido-nucleotides (100 microM) irreversibly inhibited and to a similar extent, between 40 and 55%, each of ecto-nucleotidase activities. UV photoactivation in the presence of nucleotides in the same concentration range was an effective protection from the inhibition. PMID- 8215446 TI - Interaction of the amino-terminus of an influenza virus protein with mitochondria. AB - Reye's Syndrome is characterized in part by liver mitochondrial damage. Previous studies in an animal model have demonstrated the presence of viral antigens in hepatocytes, but replication of the virus does not occur. Evidence is presented in this paper for the interaction of an influenza virus protein with mitochondria as a mechanism for mitochondrial damage in Reye's Syndrome. The amino-terminal 22 amino acids of the PB2 protein of influenza A interact with mitochondria alone (5 micrograms/mg mitochondrial protein) and, when conjugated to bovine serum albumin, mediate the binding of BSA to mitochondria (14 micrograms/mg mitochondrial protein). PMID- 8215447 TI - Purification and characterization of a mannose-specific lectin from Shallot (Allium ascalonicum) bulbs. AB - A new mannose-binding lectin was isolated from shallot (Allium ascalonicum) bulbs by affinity chromatography on an immobilized D-mannose column. The lectin (A. ascalonicum agglutinin, AAA) appeared homogeneous by polyacrylamide gel electrophoresis at pH 4.3 and gave a single protein band with an apparent M(r) of 11 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a single symmetrical peak of 11 kDa by gel filtration on a Sephacryl S-200 HR column, indicating that AAA exists as a monomeric protein at neutral pH under the gel filtration condition employed. However, chemical cross-linking studies revealed that some degree of self-association of the lectin molecules occurs and that the lectin exists in solution as a mixture of monomers and oligomers. Scatchard analysis of equilibrium dialysis data showed the presence of one carbohydrate binding site for Man (alpha 1-3) Man-alpha-O-Me per monomer, with Ka = 1.62 x 10(4) M-1. The carbohydrate-binding properties of the purified AAA were investigated by quantitative precipitation and hapten inhibition assays. Purified AAA precipitated asialofetuin, asialotransferrin, asialothyroglobulin, asialoorosomucoid, as well as their agalacto derivatives, but did not precipitate either sialylated glycoproteins or mucins. AAA also reacted strongly with the highly branched yeast mannan obtained from Saccharomyces cerevisiae. Of the monosaccharides tested only D-mannose was a hapten inhibitor of the AAA asialofetuin precipitation system, whereas D-glucose, D-altrose, D-talose, N acetyl-D-mannosamine, and derivatives of D-mannose, including 2-deoxy-, 2-deoxy-2 fluoro-, 3-deoxy-, and 6-deoxy-D-mannose were noninhibitors. These results suggest that the presence of equatorial hydroxyl groups at the C-3 and C-4 positions, an axial hydroxyl group at the C-2 position, and a free hydroxyl group at the C-6 position of the pyranose ring are the most important loci for the binding of D-mannose to AAA. Of the oligosaccharides tested, the best inhibitors were oligosaccharides containing terminal Man(alpha 1-6) [Man(alpha 1-3)]Man groups. Oligosaccharides containing either Man(alpha 1-3)Man or Man(alpha 1-6)Man units were also moderately good inhibitors of the AAA-asialofetuin precipitation system. These results indicate that AAA has an extended carbohydrate-binding site, which is most complementary to a branched mannotriosyl residue, i.e., Man(alpha 1-6)[Man(alpha 1-3)]Man.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8215448 TI - Characterization of the rat hemoglobin thiyl free radical formed upon reaction with phenylhydrazine. AB - The characterization of the radical formed from rat hemoglobin (Hb) by methemoglobin-generating agents and trapped by 5,5-dimethyl-1-pyrroline N-oxide (DMPO) has shown it to be a thiyl radical. The two-electron oxidation of hemoglobin forms a ferryl species with one or more free radicals located on the globin moiety. While the radical species has not been observed by use of uv visible spectrophotometry, the species can be detected by use of electron paramagnetic resonance spectroscopy (EPR). In previous studies, in vitro experiments have shown that the EPR signal from the rat Hb radical adduct formed by t-butyl hydroperoxide decreased following pretreatment of the oxyHb with thiol blocking agents except for iodoacetamide. In this study the power saturation profile of the DMPO radical adduct obtained from the reaction of rat oxyHb with phenylhydrazine exhibited a pattern similar to that obtained from human oxyHb, in which the beta-93 cysteine was labeled with 2,2,6,6-tetramethyl-1-piperidinyloxy 4-maleimide (4-maleimide-TEMPO). EPR spectra were taken at 77 K and computer simulations were performed. The calculated value for a(iso)N obtained by simulation indicates that the radical adduct is in a hydrophobic region. The value for a(iso)H has little structural significance, as the steric effect of the protein makes comparison with radical adducts in solution problematical. The value of gx from the rat Hb radical adduct was significantly higher than that obtained from bovine Hb, whose radical is not thiol-derived, as demonstrated by negative thiol-blocking agent experiments. A higher gx value is consistent with the radical adduct containing a heavy atom such as sulfur. Rat Hb was analyzed for thiol content by use of iodoacetamide, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) and uv-visible spectrophotometry. It was found that 1.15 +/- 0.34 thiols/tetramer of Hb were reactive with DTNB, but not iodoacetamide. PMID- 8215449 TI - Expression of modified cytochrome P450 2C10 (2C9) in Escherichia coli, purification, and reconstitution of catalytic activity. AB - The human cytochrome P450 (P450) 2C gene family is complex and heterologous expression methods are needed to facilitate the isolation of individual P450 proteins and the elucidation of their catalytic specificities. We prepared a series of constructs of P450 2C10 in the plasmid vector pCW, with modification of the 5' end of the coding sequence of the cDNA. Some were not expressed at all in Escherichia coli; two were expressed at levels of 5-20 nmol membrane-bound P450 (liter culture)-1--one (2C1028) with original codons 2-7 altered by substitution of the 5'-terminal sequence described by Barnes et al. (Barnes, H. J., Arlotto, M. P., and Waterman, M. R., Proc., Natl. Acad. Sci. USA 88, 5597-5601, 1991) and one (2C1029) with original codon 2 modified, codons 3-20 deleted, and alteration of the immediate downstream codons. In both cases the P450 2C10 proteins were found essentially only in the bacterial membranes. These proteins could be purified to a high degree by solubilization and a single DEAE chromatography step. Typical P450 Fe2+.CO absorption spectra were observed in the bacterial membranes and the purified preparations. The P450 2C1029 protein was found to have its N-terminal Met removed and the expected residues 2 (Ala)-24 were identified by amino acid sequence analysis. However, the other P450 (2C1028) was apparently blocked at the N-terminus. Three native P450 2C9/10 preparations isolated from human liver showed the expected sequences (beginning with Met) for at least the first 17 residues. The blocked N-terminus in the P450 2C1028 protein may be the result of the MALLLAVF sequence, which was also used in the expression of P450 3A4 and resulted in a blocked protein. Catalytic activities of P450 2C1028 and P450 2C1029 for tolbutamide hydroxylation were similar to those measured with purified liver P450 C29/10 in the presence of cytochrome b5, although the effect of cytochrome b5 did not always show the same pattern as with the isolated liver enzyme. The recombinant P450 2C10 enzymes did not catalyze (S) mephenytoin 4'-hydroxylation. PMID- 8215450 TI - Substrate specificity of the heparin lyases from Flavobacterium heparinum. AB - A detailed knowledge about the substrate specificities of the heparin lyases is necessary when using these enzymes as tools for elucidating the sequence of heparin and heparan sulfate. The substrate specificity of heparin lyases I, II, and III have been profiled with structurally defined, heparin-derived oligosaccharides. The primary substrate specificities of heparin lyases I and III require the presence of 2-O-sulfated alpha-L-idopyranosyluronic acid and beta-D glucopyranosyluronic acid residues, respectively, at the linkages being cleaved. Heparin lyase II demonstrates an intriguingly broad primary specificity for oligosaccharides, acting at linkages containing alpha-L-idopyranosyluronic and beta-D-glucopyranosyluronic acid as well as at linkages containing alpha-L galactopyranosyluronic acid residues. In addition to their primary specificities, each lyase also demonstrates secondary specificities under forcing conditions. Differences in the sulfation pattern within uronic acid residues and sulfation of adjacent residues has profound impact on the ease of lyase cleavage of a glycosidic linkage. Specifically, heparin lyases I and III exhibit secondary specificity for oligosaccharides containing an unsulfated alpha-L idopyranosyluronic acid residue. The lack of sulfation on residues adjacent to the linkage undergoing cleavage increases the action of heparin lyase III on a glycosidic linkage. In contrast, reduced sulfation on adjacent residues make glycosidic linkage resistant to heparin lyase I. The primary and secondary specificity can be rationalized on the basis of most favorable solution conformation of the uronic acid residues. PMID- 8215451 TI - Identification of 5-keto-(7E,9E,11Z,14Z)-eicosatetraenoic acid as a novel nonenzymatic rearrangement product of leukotriene A4. AB - Leukotriene A4 (LTA4), the reaction product of 5-lipoxygenase in human polymorphonuclear (PMN) leukocytes, is transformed both to LTB4 and a mixture of 5,6- and 5,12-dihydroxy-eicosatetraenoic acids (diHETE) via nonenzymatic hydrolysis. Evidence has been obtained that LTA4 is also converted to 5-keto (7E,9E,11Z,14Z)-eicosatetraenoic acid (5-oxo-ETE). The compound was isolated from the products of the 5-lipoxygenase reaction and its structure elucidated by UV spectroscopy, LC-MS, two-dimensional [1H]NMR spectroscopy and chemical reduction to the corresponding alcohol. The 5-oxo-ETE represented about 14% of the LTA4 hydrolysis products as compared to 72 and 14% for the 5,12-diHETE and 5,6-diHETE, respectively. A similar profile of hydrolysis products was obtained after incubation of synthetic LTA4 in aqueous buffer. Human PMN leukocytes produced 5 oxo-ETE in an arachidonic acid-dependent and MK-886-inhibitable manner. The 5-oxo ETE caused 50% inhibition of 5-lipoxygenase activity at 1 microM. These results demonstrate that the nonenzymatic conversion of LTA4, in addition to the previously described hydrolysis products, yields 5-oxo-ETE during both the 5 lipoxygenase reaction and arachidonic acid oxidation by human PMN leukocytes. They indicate that allylic epoxides can rearrange in aqueous media at physiological pH to spontaneously form beta,gamma-unsaturated ketones. PMID- 8215452 TI - Site-specific interaction of a partially purified human lens factor(s) with conserved sequences of the human gamma crystallin gene. AB - In an attempt to understand the molecular mechanisms governing the cell-type specific expression of human gamma crystallin genes we have analyzed human lens extract for the presence of factors which specifically interact with the regulatory regions. Our analyses indicate that a partially purified fraction contains an activity which specifically recognizes the proximal domain (-46 to 26) of the human gamma crystallin gene. This conserved region has been previously shown to function as a strong transcriptional activator of the mouse gamma crystallin gene. Methylation interference experiments further suggest that the factor makes contact with several G residues within this protected region. A similar (but not necessarily identical) activity is also found to be present in HeLa cell, lens epithelial cell and retinal pigment epithelial cell extracts. However, no such activity is detectable in nonlens fibroblast extract. Further characterization of the proteins reveals that the lens factor differs in its physical properties from that of the HeLa factor. These results demonstrate the presence of a candidate regulatory factor(s) in human lens which may be directly or indirectly involved in modulating the tissue-specific expression of the human gamma crystallin gene. PMID- 8215453 TI - Purification and immunological analysis of phospholipase D from castor bean endosperm. AB - Phospholipase D (EC 3.1.4.4) has been implicated in diverse cellular processes, but its physiological role is not well established in plants. In order to develop immunological and molecular biology approaches to address the problem, we report here the immunological analysis and N-terminal amino acid sequence of a cytosolic phospholipase D from castor bean (Ricinus communis L.). The enzyme was purified to apparent homogeneity from germinating castor bean endosperm. The specific activity of the purified enzyme was enhanced by approximately 670-fold with an overall yield of 4%. Its molecular mass was estimated at 92 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of this enzyme was KLVENIEETVGFGKG. Polyclonal antibodies were raised against the purified enzyme. The antibodies inhibited the activity of transphosphatidylation more than that of hydrolysis of phospholipase D. The differential effect on the two activities of this enzyme implies that different active sites on this enzyme may be involved in the two reactions. Immunoblot analyses showed that the amounts of phospholipase D protein relative to the total endosperm proteins increased during the first 5 days of germination. The antibodies cross-reacted to proteins from several tested plant species, and those proteins had molecular masses similar to that of castor bean phospholipase D. These results indicate that the expression of phospholipase D in castor bean changes according to growth stages and that phospholipase D enzymes of different plant species are structurally related. PMID- 8215454 TI - The role of water in the dissociation of enolase, a dimeric enzyme. AB - Exposure of enolase to hydrostatic pressure results in a reversible inactivation of the enzyme; increasing the osmotic pressure, by adding glycerol, glucose, or sucrose to the solutions stabilizes the enzyme against the effects of hydrostatic pressure. The effects of both hydrostatic and osmotic pressure on the rate of inactivation have been determined. As hydrostatic pressure increases, the rate of inactivation increases. As osmotic pressure increases, the rate of inactivation decreases. We have interpreted these results using the following model: hydrostatic pressure causes the active, dimeric enzyme to dissociate into inactive monomers; during the dissociation, the subunit interfaces become hydrated. As osmotic pressure increases, hydration becomes more difficult and dissociation is reduced. The combined effects of hydrostatic and osmotic pressure suggest that much of this hydration occurs during formation of the transition state. PMID- 8215455 TI - The main chain dynamics of a peptide bound to calmodulin. AB - The main chain dynamics of a peptide corresponding to the smooth muscle myosin light chain kinase calmodulin-binding domain bound to calcium-saturated calmodulin have been studied by 15N relaxation techniques. Laboratory and rotating-frame spin lattice relaxation times and nuclear Overhauser effects have been determined for nine amide 15N sites in the peptide using two-dimensional NMR spectroscopy. The global motion of the 1:1 complex is shown to be isotropic and is characterized by a correlation time of 10 ns rad-1. The generalized order parameters (S2) of the nine backbone amide N-H vectors of the peptide all fall closely about a value of 0.83. The corresponding effective correlation times all tend to zero, indicating that, on the subnanosecond time scale, backbone motion of the bound peptide is highly restricted and dominated by extremely fast motions. PMID- 8215456 TI - Transient proton uptake and release is associated with the photocycle of the photoactive yellow protein from the purple phototrophic bacterium Ectothiorhodospira halophila. AB - Upon excitation by a laser flash at 445 nm, the photoactive yellow protein (PYP) undergoes a bleach and red-shift occurring in less than 10 ns, undergoes a further bleach in approximately 200 microseconds, and then recolors in approximately 200 ms. A conformational change occurs during photobleaching which exposes a hydrophobic site. We have now shown that this photocycle also involves a net uptake of one proton during formation of the fully bleached second intermediate, followed by an equivalent proton release upon return of PYP to the ground state. Proton uptake lags slightly behind PYP bleaching and is first order, indicating that the protein conformational change occurs in two steps. The results suggest that a basic residue which is normally buried in the protein interior is transiently exposed to solvent during the PYP photocycle and, as a consequence, undergoes a change in pK. On the basis of the crystal structure of PYP, we propose that this basic residue is lysine 111. PMID- 8215457 TI - Effects of paraquat on Escherichia coli: sensitivity to small changes in pH of the medium--a cautionary note. AB - Uric acid appears to protect Escherichia coli against the growth-inhibiting effect of paraquat, but this is actually due to acidification of the medium and does not occur when the pH of the medium is readjusted to neutrality. Any compound which lowers the pH of the medium will thus diminish the effect of paraquat on E. coli, whether that effect is inhibition of growth or adaptive induction of members of the soxRS regulon. PMID- 8215458 TI - Hydrophobic side chain requirements for lauric acid and progesterone hydroxylation at amino acid 113 in cytochrome P450 2C2, a potential determinant of substrate specificity. AB - To determine the requirements for hydrophobic amino acids at position 113 in cytochrome P450 2C2, a series of hydrophobic and uncharged polar amino acids was substituted for isoleucine in P450 2C2 and in C2MstC1, a chimera of P450 2C2 and P450 2C1. Lauric acid hydroxylase activity was determined in COS1 cells transfected with P450 2C2 mutants and both lauric acid and progesterone hydroxylase activities were determined for C2MstC1 variants. In P450 2C2, 40 to 120% of the wild type (omega-1) lauric acid hydroxylase activity was retained in all hydrophobic mutants, but activity was reduced to near background by substitutions of the polar amino acids, tyrosine and cysteine. Likewise, in C2MstC1 mutants, hydrophobic substitutions were 20 to 50% as active as wild type for lauric acid hydroxylation, and polar amino acids again resulted in strong reductions of activity. In contrast, a different pattern of activity for progesterone C21-hydroxylase was observed for C2MstC1 mutants. A valine substitution had a modest effect on activity but substitutions of leucine and alanine reduced progesterone C21-hydroxylase activity 5- to 7-fold, respectively, and the large hydrophobic amino acid, phenylalanine, reduced activity about 30 fold. No changes in the regiospecificity of progesterone hydroxylation were observed for any of the mutants. Similar steady-state levels of immunoprecipitated, radiolabeled protein were observed for each mutant except for the glycine substitution which resulted in degradation of the protein. The different patterns of the effects of the mutations on progesterone and lauric acid hydroxylase activity provide additional support for the critical role of residue 113 in substrate recognition. The low activities in mutant proteins with hydrophilic amino acid substitutions indicate that the hydrophobic nature of this residue is important. The hydrophobic requirements are more stringent for a larger, more rigid steroid substrate than for a saturated fatty acid with a flexible hydrocarbon tail. PMID- 8215459 TI - Heparin-von Willebrand factor binding as assessed by isothermal titration calorimetry and by affinity fractionation of heparins using synthetic peptides. AB - The ability of proteins to bind heparin, a heterogeneous sulfated glycosaminoglycan, likely depends on the conformational uniqueness of specific binding domains. Based on the motif of a consensus heparin-binding synthetic peptide, a 23-residue sequence (Y565-A587) of human von Willebrand factor (vWF) was previously identified which binds heparin with affinity comparable to that of the native protein (Sobel, M., Soler, D. F., Kermode, J. C., and Harris, R. B. 1992 J. Biol. Chem. 267, 8857-8862). This peptide undergoes a conformational change upon binding heparin. Isothermal titration calorimetry has now been used to further quantify this binding reaction. In experiments done at 25 degrees C, Y565-A587 bound heparin with about the same affinity (Kd = 9.0 x 10(-7) M) as a "core" sequence peptide encompassing residues K569-I580. Binding between these peptides and heparin is overwhelmingly enthalpically favored and is dependent on the formation of productive electrostatic bonds; hydrophobic interactions do not play a significant role in mediating binding. Furthermore, when immobilized on Sepharose in a manner which does not compromise essential cationic residues, the vWF domain peptides are effective affinity ligands. They bind a species of heparin which possesses significantly enhanced affinity for native vWF. The Kd for binding between the high-affinity heparin and Y565-A587 is about threefold lower than that determined with crude, unfractionated heparin. Thus, the vWF peptides are a useful model for studying the physiological role of heparin binding to the native protein. PMID- 8215461 TI - [Antisense DNA]. AB - Antisense DNA has been given a big attention as future therapeutic reagents. However, there are several shortcomings including biological instability and low membrane permeability. In order to overcome these shortcomings, the first generation of oligonucleotides has been synthesized. The efficacy of these analogues in vitro or in vivo seems to be promising. In this reviewing article, we mainly describe the intracellular delivery of oligonucleotides from the pharmaceutical point of view. PMID- 8215460 TI - The 85-kDa, arachidonic acid-specific phospholipase A2 is expressed as an activated phosphoprotein in Sf9 cells. AB - A human, 85-kDa arachidonoyl-specific, cytosolic phospholipase A2 was expressed using the baculovirus-insect cell expression system. Expression resulted in the production of an active protein which consisted of approximately 3% of the total protein in the host Spodoptera frugiperda (Sf9) cells at 67 h after infection. The phospholipase A2 was purified to apparent homogeneity and exhibited calcium dependent phospholipase A2 activity with a specific activity of 8 mumol/min/mg protein, as well as calcium-independent lysophospholipase activity with a specific activity of 17 mumol/min/mg protein. The phospholipase A2 was expressed as a phosphoprotein and was primarily phosphorylated on serine residues. Phosphatase treatment of the recombinant phospholipase A2 resulted in dephosphorylation of the enzyme and a 63% decrease in phospholipase A2 activity. This decrease in activity is similar in magnitude to the decrease in activity observed with phosphatase-treated phospholipase A2 from stimulated mammalian cells. These data demonstrate that the 85-kDa phospholipase A2 is expressed as an activated phosphoprotein in Sf9 cells. PMID- 8215462 TI - [Chemotherapy for osteosarcoma--trends in recent years]. AB - Therapy for osteosarcoma has changed considerably over the last two decades. We reviewed 49 cases of osteosarcoma treated in our department after 1970 and examined the present status of chemotherapy, results and the side effects. We classified the 49 cases according to treatment policy into 4 groups by age. 1) 11 cases before 1977 did not receive systematic therapy with high dose-methotrexate (HD-MTX) and such. 2) 10 cases between 1977 and 1982 were basically given HD-MTX therapy alone. 3) 15 cases between 1977 and 1982 were given preoperative HD-MTX therapy, and cisplatin (CDDP) after surgery, if necessary. 4) After 1988, patients received MTX together with CDDP before surgery and ifosfamide (IFO) or newly developed drugs, if necessary. The results for those treated after 1988 were superior to those for patients treated earlier. Further efforts to develop a more effective therapy are being made, since even present therapies have many problems. PMID- 8215464 TI - [Intra-arterial versus intra-venous infusion as a preoperative chemotherapy for bone and soft tissue sarcomas]. AB - The literatures concerning intra-arterial versus intra-venous infusion as a preoperative chemotherapy for bone and soft tissue sarcomas were reviewed in this paper. The initial purpose of the therapies are to give the surgeons useful and helpful preparation for limb salvage surgery. Otherwise, they are also useful to evaluate the efficacy of the chemotherapeutic agents. However, it takes a few months for the therapy to be able to evaluate the response to the tumors and the therapy do not always have good response, therefore, it is important to pay a great care in performing the therapy. From the literatures, it is difficult to clarify the differences of each methods because of the variable histological results. Some authors report the higher local concentration of the agents in intra-arterial infusion. Arterial infusion have to be indicated as a locally useful method with a attention to systemic therapy. PMID- 8215463 TI - [Chemotherapy for Ewing's sarcoma, malignant fibrous histiocytoma and malignant lymphoma]. AB - Recent advances in adjuvant chemotherapy for malignant bone tumor have been improving the survival rate and making limb-salvage surgery a reliable technique. Ewing's sarcoma is treated by multiple agent chemotherapy. We treat Ewing's sarcoma by Rosen's T-11 protocol (CYT.ADM.MTX.VCR.ACT-D.BLM). This protocol is very effective, but results are poorer than for osteosarcoma. Newly developed protocols such as EICESS (European Intergroup Cooperative Ewing's Sarcoma Study) 92, including new drugs, should be investigated. The results with malignant fibrous histiocytoma are comparable to those for osteosarcoma. We have performed an original chemotherapy protocol, called "K-1 protocol." Patients were treated with three courses of intraarterial infusion of cisplatin (120 mg/m2) and caffeine (1.0-1.5 mg/m2/day for three days continuously) at two-week intervals. If the effect was insufficient, ADM (30 mg/m2/day for two days continuously) is added to this protocol. We treat malignant lymphoma in collaboration with a hematologist and radiologist. The 5-year survival rate of non-Hodgkin's lymphoma in our series was 56% in clinical stage III and 34% in clinical stage IV. We are trying third-generation chemotherapy to improve the survival rate. PMID- 8215465 TI - [The significance of preoperative chemotherapy for thermopreservation of limbs]. AB - Preoperative chemotherapeutic effects on 42 osteosarcomas treated with CDDP intra arterial infusion protocol were compared with the effects of treatment of same by local perfusion only, following administration of adriamycin (ADR) or high doses methotrexate and leucovorin (HD-MTX). Thirteen cases were further given local hyperthermic perfusion (LHP) treatment. The preoperative local treatment resulted in a poor response in cases in which the serum ALP failed to fall down the normal range, those with angiographically demonstrated tumor stains remaining, and those with reactive zones remaining as indicated by T2 MR imaging. The ratios of necrotic areas were significantly higher in the LHP group, while those of viable areas were significantly lower in the LHP group compared to other groups. Total tumor cell killing was possible in six of 13 cases in the LHP group. Post necrotic fibrosis and post-necrotic osteosclerosis were significantly higher in the LPH group. The results suggested that, in selected cases treated with LHP, conservative surgery may well be possible so as to preserve all functional activity. PMID- 8215466 TI - [Chemotherapy for soft tissue sarcoma--current concepts and review]. AB - The role of chemotherapy for soft tissue sarcoma with the exception of rhabdomyosarcoma remains controversial. Several randomized trials have suggested only doxorubicin (ADR) and ifosfamide produced a single-agent response rate above 20% in advanced sarcoma. As a combination chemotherapy, the doxorubicin-based combination, ADR + DTIC (ADIC) and CYVADIC, showed a higher response rate. Ifosfamide in addition to doxorubicin (Ifos + ADR or ADIC) appeared to have major activity with a higher complication rate. The role and value of adjuvant chemotherapy have not yet been established. Most randomized studies have suggested that no survival benefit was observed in the chemotherapy group relative to the control group. Further basic and clinical investigation is necessary to obtain a better prognosis in high-grade malignant soft tissue sarcoma. PMID- 8215467 TI - [In vitro chemosensitivity test of human renal cell carcinoma using three dimensional gel-supported culture system]. AB - Surgical tumor specimens obtained from twenty-five patients with renal cell carcinoma were subjected to the gel-supported culture developed by Hoffman for a clinical approach. Cell viability was determined by exposure to 3H-thymidine. The anti-cancer drugs examined in this set were 13 in total: ADM, AMR, BLM, MMC, VCR, VLB, etoposide, CDDP, 5-FU, MTX, IFN-alpha, IFN-gamma and TNF. The specimens were exposed to media containing 1x and 1/10x achievable human plasma peak concentrations of the agents. The overall susceptibility rate for growing tumors obtained from patients was 88% (22 of 25 patients). Susceptibility (less than 50% of control 3H-thymidine uptake) to ADM was observed to be highest (56%) in 12 of 22 patients, and to VLB and BLM (50%) in 11 patients each. On the other hand, that to MTX was observed in 1 patient at the lowest rate (5%), and that to the BRM group drugs was observed in 3 in IFN-alpha (14%), 1 in IFN-gamma (5%) and 2 in TNF (9%). However the number of effective drugs was not correlated to the grade, architecture and cell type. These results suggest that this assay system may be useful for a chemosensitivity test. PMID- 8215468 TI - [Relationship between tissue concentrations of 5-FU and degeneration of tissues after UFT administration in patients with bladder tumor]. AB - The relationship between the 5-FU concentration and tissue degeneration was studied in the bladder tumor tissue after UFT administration. In 12 patients with bladder tumor, UFT 400 mg/day was administered orally for about 2 weeks before TUR, and tegaful, 5-FU and uracil concentrations were examined in the blood and the tumor tissue taken about 6 hours after the last administration. Tumor tissue was also taken before and after the UFT administration, and the degree of cell degeneration due to UFT administration were evaluated by light and electron microscopy. The 5-FU concentration was significantly higher in the tumor tissue (0.078 +/- 0.091 microgram/g) than in the serum (0.017 +/- 0.010 microgram/ml). Signs of degeneration were observed in tumor cells after UFT administration in all 6 patients in whom the tumor tissue 5-FU concentration was 0.046 microgram/g or higher. Mitosis was not increased after UFT administration in any of the 12 patients. PMID- 8215469 TI - [Effect of UFT and CBDCA combined therapy on human laryngeal cancer transplanted into nude mice]. AB - Nude mice transplanted with a human tumor of the larynx were treated by combination therapy with UFT and carboplatin (CBDCA) for a prolonged period (3 months). To compare the combination therapy with UFT or CBDCA treatment alone, the mice were divided into four groups; control group, group orally given UFT (20mg/kg, five times a week for 3 months), group intraperitoneally given ip CBDCA (50mg/kg, every 3 weeks for 3 months), and group given combination therapy with UFT and CBDCA. No antitumor effect was observed in the group received UFT or CBDCA alone, while a significant antitumor effect was noted in the combination therapy group, compared to the control as evidenced by DNA histogram, showing a decrease in atypical cell count. The results of this study suggest that the combination of UFT and CBDCA provides an efficacious chemotherapy for cancers of the head and neck. PMID- 8215470 TI - [Effects of cisplatin, carboplatin, etoposide and human hepatocyte growth factor on the colony formation of four human liver cancer cell lines]. AB - Antitumor activity of cisplatin, carboplatin, etoposide, or human hepatocyte growth factor (hHGF), was compared by examining the colony formation ability of four liver cancer cell lines (PLC/PRF/5 and HuH-7, hepatocellular carcinoma; HuH 6 and HepG2, hepatoblastoma). Antitumor activity was evaluated from the drug concentration causing 50% cell death by a colony assay. PLC/PRF/5 cells were most effectively killed by cisplatin and etoposide, HuH-7 cells by cisplatin and carboplatin, HuH-6 cells by etoposide, and Hep G2 cells by cisplatin. These results indicate that among four liver cancer cell lines, the three were the most sensitive to cisplatin, the two were to etoposide and the only one cell line was to carboplatin. There was no significant relationship between each drug and types of liver cancer. Combined treatment with cisplatin (0.01-1.0 microgram/ml) and etoposide (0.1 microgram/ml) showed synergistic cytotoxic effects on the colony formation of PLC/PRF/5 cells, while combination of carboplatin (0.01-0.1 microgram/ml) and etoposide (0.1 microgram/ml) caused subadditive cytotoxic effects. hHGF stimulated the colony formation of HuH-6 cells, while it inhibited that of Hep G2 cells. The treatment of HuH-6 with cisplatin and hHGF showed a higher cell survival percentage compared with the treatment with cisplatin alone. On the other hand, cell survival of Hep G2 cells was remarkably decreased by the combined treatment with cisplatin and hHGF. PMID- 8215471 TI - [Reservoir system implantation technique via the inferior epigastric artery for local recurrence of rectal cancer]. AB - A reservoir system was implanted via the inferior epigastric artery into the internal iliac artery for local recurrence of rectal cancer under lumbar anesthesia. At the same time, the internal iliac artery on the opposite side of the tumor and the superior and inferior gluteal artery on the tumor side were embolized by gelform and coil. Five-hour continuous intraarterial infusion of 1,000 mg/m2 of 5-FU with intravenous drip infusion of 20 mg/m2 of leucovorin and one shot intraarterial infusion of 50 mg/m2 of cisplatin were performed as the treatment. This technique allows easier insertion of the catheter than by the conventional method, elevates the anticancer drug levels in the pelvic cavity and prevents ulcer of the buttocks and perineum. The technique is considered an effective form of treatment for local recurrence of rectal cancer. PMID- 8215472 TI - [Chemotherapy with high-dose carboplatin for inoperable non-small cell lung cancer]. AB - The clinical efficacy and side effects of high-dose CBDCA therapy were studied in 35 cases of inoperable non-small cell lung cancer. A positive effect was obtained in about 30% of the subjects, all of who were squamous cell carcinoma patients. Incidence of clinical side effects was very low, thrombocytopenia being the major hematologic side effect. AUC, calculated from periodic measurements of free-Pt concentration in 19 subjects, was sensitive renal function, having a positive correlation with Cmax and a negative correlation with platelet nadir levels. This finding suggested the importance of establishing optimum dose levels with regard to pharmacokinetics. Patients in whom bone marrow suppression did not hamper continued therapy were treated as outpatients, many of whom retained sufficient QOL while undergoing outpatient therapy. Considering the present status of chemotherapy for NSCLC, characterized by the lack of long-term clinical efficacy and the presence of severe side effects, the present therapy is of great importance, since it can be continued with constant efficacy rates while maintaining good PS. PMID- 8215473 TI - [Intensive 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) and cryopreserved autologous bone marrow transplantation]. AB - High-dose ACNU followed by autologous bone marrow transplantation was administered alone or together with other agents such as cyclophosphamide, dacarbazine, carboquone or/and VP-16. The starting dose of ACNU was 200 mg/m2, with gradual escalation up to 400 mg/m2. Median duration of granulocytes of less than 100/mm3 and platelets of less than 30,000/mm3 was 4.5 days (range; 0-9) and 10.5 days (range; 0-43), respectively. Bacteremia occurred in 4 cases, but no case of pneumonia was encountered. Heart failure possibly due to the cyclophosphamide was noted in one case with arrhythmia. Out of 13 cases with measurable diseases, three patients with Hodgkin's disease, two patients with diffuse lymphoma, and one patient with follicular lymphoma attained a complete response. Partial response was obtained in two patients with non-Hodgkin's lymphoma. Two patients with melanoma and one with acute nonlymphocytic leukemia without measurable disease still remain disease-free. PMID- 8215474 TI - [A late phase II comparative study of idarubicin + cytarabine and daunorubicin + cytarabine in adult patients with acute non-lymphocytic leukemia. Idarubicin Study Group]. AB - In adult patients with acute non-lymphocytic leukemia (ANLL), idarubicin (IDA) and daunorubicin (DNR) were compared for efficacy and safety in combination with cytarabine (Ara-C). IDA 12 mg/m2/day and DNR 40 mg/m2/day were administered iv bolus for 3 consecutive days (day 1-3), respectively, in combination with Ara-C 80 mg/m2 given by 2-hour intravenous infusion, every 12 hours for 7 consecutive days. The number of evaluable patients was 32 for each group previously untreated. The rates of complete remission (CR) were 59.4% (19/32) in the IDA group and 40.6% (13/32) in the DNR group. The clinical equivalence test with delta = 10% demonstrated that the IDA group is equal or superior in remission rates (p = 0.010) compared to the DNR group. In addition, the Cochran-Mantel Haenszel test for response means with scores of 3 (CR), 2 (PR) and 1 (NR) showed the significant superiority (p = 0.044) of the IDA group to the DNR group. The duration needed to attain less than 5% leukemic cells in bone marrow tended to be shorter in the IDA group (p = 0.072), and in the CR patients the number of days needed to reach the nadir value in leukemic cells were significantly fewer in the IDA group (p = 0.037). The nadir value of WBC was significantly lower in the IDA group (p = 0.022). As for adverse reactions, high incidences of diarrhea and stomatitis were observed in the IDA group, while the incidences of other adverse reactions were similar between the two groups. When effects of the drug on the ECG were examined, significant changes in ECG parameters were observed in the DNR group after treatment but not in the IDA group. From the above, remission induction in adult AN LL, IDA + Ara-C therapy showed better efficacy than DNR + Ara-C therapy, and IDA was considered to be a drug of first choice in the treatment of ANLL patients. PMID- 8215475 TI - [A late phase II study of idarubicin hydrochloride in adult patients with acute lymphocytic leukemia. Idarubicin Study Group]. AB - A late phase II study of idarubicin hydrochloride combined with vincristine and prednisolone was conducted in adult patients with acute lymphocytic leukemia (ALL) in the first relapse as a multi-center joint research project. The dosages used were idarubicin 12 mg/m2/day i.v. for 3 consecutive days (day 1-3), vincristine 1.4 mg/m2 i.v. (day 1) and prednisolone 60 mg/m2/day po for 5 consecutive days (day 1-5). The number of evaluable patients was 20. The patients showed responses including 3 complete remissions (CR) and 10 partial remissions (PR), with an efficacy rate (CR + PR) of 65.0%. Adverse reactions occurred in 19 of 20 patients. The main symptoms were gastrointestinal symptoms including anorexia, nausea/vomiting, and stomatitis and fever, infection, and alopecia. Abnormal laboratory data were observed in 6 of 20 patients with 13 events. Although one case of an increase in GPT with WHO grade 3 was observed, the other cases were not of significance. From the above study, idarubicin hydrochloride was considered to be effective in relapsed ALL patients in combination therapy with vincristine and prednisolone. PMID- 8215476 TI - [Multi-center cooperative phase II study of combined infusion of PJ-203 (degradable starch microspheres) into hepatic artery in metastatic liver cancer]. AB - In the present multi-center cooperative phase II study, in which 16 institutions participated, PJ-203 and mitomycin C were concomitantly infused into the hepatic artery of patients with metastatic liver cancer and the tumor response and safety of the combined therapy were examined. Of 81 patients treated with PJ-203, 52 patients were complete cases in which bidimensionally measurable lesions could be assessed for anticancer effect in accordance with the Direct Evaluation Criteria of Chemotherapy. The number of treatments given to the complete cases until the assessment of therapeutic effect ranged from 1 to 11 times, with the mean of 3.1 times. The overall response rate was 48.1% (25/52). The response rate for each primary lesion was 68.8% (11/16) for stomach cancer, 40.7% (11/27) for colorectal cancer and 33.3% (3/9) for other types of cancer including the gallbladder. The 25 patients with CR or PR, a 50% decrease in tumor size was confirmed after the treatment ranged from 1 to 5 times, with the treatment periods of 2 to 3 weeks. Adverse reactions were found in 56 (69.1%) out of 81 patients assessed for safety. Relatively frequent symptoms were pain in 49.4% (40/81), nausea and vomiting in 33.3% (27/81), fever in 30.9% (25/81) and anorexia in 6.2% (5/81). Principal abnormal laboratory values included a transient elevation of GOT (26.3%), GPT (22.5%), LDH (12.7%) and Al-p (8.8%). Blockade of blood flow could be observed by angiography when the amount of PJ-203 infused was in the range from 180 to 900 mg as degradable starch microspheres. The blood flow blockade could be observed most frequently at the amount of 600 mg (37.7%). The period attaining over 50% of tumor response in 25 complete cases was 42 days as a median. After the treatment was initiated in 81 patients, 50% survival duration and one-year survival rate averaged 277 days and 35.7%, respectively. The corresponding figures for each primary cancer were 419 days and 51.0% for patients with liver cancer metastasized from colorectal cancer, against 239 days and 11.8% for those with liver cancer metastasized from stomach cancer. PMID- 8215477 TI - [Comparative clinical study in metastatic liver cancer between intra-arterial infusion of mitomycin C alone and intra-arterial infusion of mitomycin C combined with PJ-203 (degradable starch microspheres)]. AB - In the present comparative study, we examined an intra-arterial chemotherapy combined with PJ-203 in 60 patients with liver cancer metastasized from gastrointestinal cancer, using an intra-arterial chemotherapy alone as the control. Sixty patients who had been registered by telephone contact were allocated to groups either treated with the intra-arterial chemotherapy alone or with PJ-203 combined, 30 patients each. Mitomycin C was used as the anticancer drug and given at the dose of 8mg/m2 per time. The dose of PJ-203 was 600 +/- 300 mg as degradable starch microspheres. A significantly higher response rate (CR + PR/complete cases) of 54.5% (p = 0.021) was noted in the PJ-203 combined group, as compared to 20.0% for the control group. The 50% survival duration was 282 and 214 days for the PJ-203 combined group and control group, respectively, with no significant difference being noted between the two groups. Principal adverse reactions such as pain, gastrointestinal symptoms and fever were statistically more frequent (p < 0.01) in the PJ-203 combined group than in the control group. Among the abnormal laboratory values, the incidence of decreased leukocytes was significantly lower (p = 0.022) in the PJ-203 combined group than in the control group. One of the patients concomitantly treated with PJ-203 died of drug-induced hepatitis, which was probably attributed to mitomycin C. However, overall utility assessment was significantly better (p = 0.002) in the PJ-203 combined group. PMID- 8215478 TI - [Comparison of granisetron alone and granisetron plus hydroxyzine hydrochloride for the prophylactic treatment of emesis induced by cisplatin-containing chemotherapy]. AB - In this study, the utility and safety of granisetron alone (Group G) and granisetron plus hydroxyzine hydrochloride (Group G/H) for nausea and vomiting were evaluated in patients with head and neck cancer treated by cisplatin containing chemotherapy. There was no statistically significant difference between the two groups in the severity of nausea or frequency of vomiting, although all patients in the G/H group showed complete response (no nausea or vomiting) from the fifth day after cisplatin administration. The clinical utility rate was higher in Group G/H than in Group G. The only side effect observed was headache in one patient from Group G. No drug-related abnormality in laboratory tests was observed. These results demonstrate that the antiemetic efficacy of granisetron can be augmented by the addition of hydroxyzine hydrochloride, providing superior control of emesis induced by cisplatin-containing chemotherapy. PMID- 8215479 TI - [Clinical effects of granisetron and methylprednisolone against nausea, vomiting and anorexia induced by cisplatin]. AB - We investigated the usefulness of concurrent therapy of granisetron with methylprednisolone sodium for on nausea, vomiting and anorexia induced by chemotherapy, including cisplatin, in patients with oral cancer. Group A: 10 patients who were on concurrent therapy of granisetron (3.0 mg/body) with methylprednisolone sodium (750 mg/body) (19 courses). Group B: 13 patients who were given coktail therapy of methylprednisolone sodium (750 mg/body) as the base drug plus metoclopramide (46.7 mg/body on average) and domperidone (82.9 mg/body on average) (21 courses). Efficacy rates for nausea, vomiting and anorexia were 89.4%, 100% and 100% in group A, and 33.3%, 47.6% and 42.9% in group B, respectively. Statistical significance was found with nausea, vomiting and anorexia (p < 0.01). The results suggest usefulness of concurrent therapy of granisetron with methylpredonisolone sodium for cisplatin-induced nausea, vomiting and anorexia. PMID- 8215480 TI - [Efficacy of the treatment of gastric cancer as neo-adjuvant chemotherapy of 48 hour continuous intravenous infusion of 5-fluorouracil (5-FU) with leucovorin (LV)]. AB - A 51-year-old female with inoperable gastric cancer and with infiltration of pancreatic tail diagnosed by abdominal CT was treated with leucovorin (LV) and 5 fluorouracil (5-FU). The regimen was: LV 30 mg/body/24 hr prior to 5-FU 1,000 mg/m2/day for 48 hrs. This treatment was repeated 6 times. After treatment, the size of tumor decreased so that the patient was able to be operated (Total gastrectomy with partial distal pancreatico-splenectomy). During the treatment, patient showed no side effect except for slight nausea. This neo-adjuvant chemotherapy might be a recommendable treatment of advanced gastric cancer. PMID- 8215481 TI - [A case of malignant fibrous histiocytoma of jejunal origin with marked response to cisplatin, ifosfamide and adriamycin]. AB - A case of malignant fibrous histiocytoma (MFH) of jejunal origin with brain and lung metastases was treated by jejunal resection. Four courses of sequential chemotherapy that combined cisplatin, ifosfamide and adriamycin were performed starting on day 20 following operation. Both brain and lung metastases showed marked reduction in size, and toxicity was minimal. PMID- 8215482 TI - [Mitomycin C associated hemolytic uremic syndrome--a case report and review of the Japanese cases]. AB - A 36-year-old man who developed hemolytic uremic syndrome (HUS) associated with mitomycin C (MMC) after the radical operation for early gastric cancer was reported. He was successfully treated with hemodialysis and transfusion of fresh frozen plasma. However, the pathogenesis and the effective treatment of this syndrome are still undetermined. The literature on MMC-induced HUS in Japan was reviewed, and the relationship between the prognosis and the patients conditions, such as sex, age, site of primary cancer, total dose of MMC, latent period from MMC administration, laboratory findings at the time of diagnosis and treatment with steroids or plasma exchange, were analysed. Patients less than 60 years old or treated with plasma exchange were found to be associated significantly with a favorable outcome. The most frequent cause of death was pulmonary edema or respiratory failure. In conclusion, early treatment with plasma exchange appeared to result in a better prognosis. PMID- 8215483 TI - [Photodynamic therapy for superficial esophageal cancer: a phase III study using PHE and excimer dye laser]. PMID- 8215484 TI - [Preliminary results of a combination therapy of irradiation, MCNU, carboplatin (CBDCA) and IFN-beta (MCI therapy) for gliomas]. PMID- 8215485 TI - [A histological observation after a short-term administration of 5'-DFUR and tamoxifen in patients with advanced breast cancer]. PMID- 8215486 TI - [Clinical significance of serum pepsinogen levels for prediction of recurrence in gastric carcinoma]. PMID- 8215487 TI - [Growth inhibition of pancreatic cancer cells by flavonoids]. PMID- 8215488 TI - [Polyethylene glycol modification to reduce the immunogenicity of monoclonal antibody]. PMID- 8215489 TI - Successful treatment of adult's Langerhans cell histiocytosis with thalidomide. Report of two cases and literature review. PMID- 8215490 TI - Acquired purpura fulminans induced by alcohol and acetaminophen. Successful treatment with heparin and vitamin K. AB - Purpura fulminans is a rare syndrome of progressive hemorrhagic necrosis of the skin that may present as a dermatologic emergency. It most commonly affects children during the convalescent phase of a streptococcal infection or a viral exanthem. In adults, it may be associated with sepsis or acquired causes. Its pathogenesis has challenged physicians for decades. It has been discovered that purpura fulminans is almost always associated with disseminated intravascular coagulation and can occur in subjects with inherited or acquired deficiencies of the protein C anticoagulant pathway. Patients with liver compromise may also be potential candidates for coagulopathies secondary to hepatic dysfunction and impaired protein synthesis. It is widely recognized that individuals who consume alcohol on a long-term basis may develop severe hepatotoxicity from ingestion of therapeutic doses of acetaminophen (500 to 1000 mg every 4 to 6 hours). We have observed a patient with chronic alcoholism in whom hepatotoxicity and purpura fulminans developed secondary to the ingestion of acetaminophen. PMID- 8215491 TI - Cyclosporine in the treatment of palmoplantar pustulosis. A randomized, double blind, placebo-controlled study. AB - BACKGROUND AND DESIGN: Palmoplantar pustulosis (PPP) is an inflammatory skin disease characterized by pustule formation, erythema, induration, and scaling of the affected skin of the palms and soles. Palmoplantar pustulosis is usually resistant to treatment. In a double-blind study (phase 1) of 4 weeks, 40 patients with PPP were randomized to receive oral cyclosporine, 2.5 mg/kg per day, or placebo. An open-label dose-finding phase 2 with cyclosporine doses of 1.25, 2.5, and 3.75 mg/kg per day was performed in the following 3 months. The patients were then followed for at least 2 months after termination of cyclosporine treatment. Response to treatment was judged by the number of fresh pustules. Patients displaying a reduction of 50% or greater in the number of pustules, compared with baseline, were defined as responders. RESULTS: Of the patients who completed phase 1, 17 of 19 patients in the cyclosporine group and four of 15 in the placebo group were classified as responders (P < .001). Cyclosporine, but not placebo, significantly reduced formation of new pustules (P = .001). In the subsequent open phase, a daily cyclosporine dose of 1.25 mg/kg appeared to be an effective treatment of PPP in approximately half of the treated patients. Many patients relapsed after initial success with cyclosporine. However, only one patient studied totally failed to respond to cyclosporine treatment. At the end of phase 3, most of the studied parameters had returned to pretreatment levels. The most common side effect was headache in the 2.5 mg/kg per day dosage group; no significant side effects were observed in the 1.25 mg/kg per day dosage group. CONCLUSIONS: Low-dose cyclosporine treatment (1.25 to 2.5 mg/kg per day) is effective in PPP. PMID- 8215492 TI - Role of sun exposure on nevus. First study in age-sex phenotype-controlled populations. AB - BACKGROUND: These studies were designed to assess the influence of sun exposure on nevi in white people. To eliminate the confounding effect of age, sex, and phenotype, two parallel studies were conducted on people of the same age (17 to 24 years; median, 20 years old), sex (male), and phenotype: one in people with "red" phenotype (red or red-blond hair, white complexion on the inner part of the arm, and inability to tan) and one in people with "dark" phenotype (brown or black hair, dark complexion on the inner part of the arm, absence of freckles, and easy tanning without burning). RESULTS: In both groups, comparison of nevus counts on the inner and outer side of the upper extremities and comparison of mean density of nevi (number per square meter) in always-exposed and never exposed skin show that the number of nevi is higher in sun-exposed areas. The density of large and atypical nevi was maximal on intermittently sun-exposed skin while the density of small nevi was maximal on always-exposed skin. The number of large nevi on intermittently exposed skin correlated with cumulative intensive exposure during beach recreation in the red phenotype group. The number of large nevi was significantly higher in red phenotypes who repeatedly experienced severe sunburns in their first 20 years of life. CONCLUSIONS: The number of nevi at the end of the second decade is influenced by cumulative sun exposure from birth. "Traumatizing" sun exposure, which is more frequent in the red phenotype than in the dark phenotype, has an influence on the number of large nevi and is therefore likely to make small nevi grow. PMID- 8215493 TI - Nonmelanoma skin cancer mortality in the United States, 1969 through 1988. AB - BACKGROUND AND DESIGN: Nonmelanoma skin cancer is the most common malignancy in the United States. Despite its importance, patterns of mortality from this cause are poorly documented. Recent insights into sources of misclassification allow for more accurate estimation of these patterns. This investigation describes nonmelanoma skin cancer mortality in the United States during 1969 through 1988 on the basis of routine death certification and adjusts reported mortality data for two major sources of misclassification. RESULTS: Nonmelanoma skin cancer mortality rates decreased by approximately 20% to 30% for both men and women and for both whites and blacks, although the decline among blacks was less consistent than among whites. Mortality was greater among men than among women and greater among whites than among blacks, although the most pronounced difference was between white men and the other three racial/gender groups studied. Approximately 1200 deaths per year are attributable to nonmelanoma skin cancer. CONCLUSIONS: Nonmelanoma skin cancer mortality is diminishing despite increasing incidence. Mortality rates among blacks are extraordinarily high in comparison with their incidence rates. More careful attention to misclassification in mortality statistics is crucial for an accurate assessment of the public health burden of nonmelanoma skin cancer. PMID- 8215494 TI - Low dose recombinant interferon alfa treatment for classic Kaposi's sarcoma. AB - BACKGROUND: High doses of interferon alfa are used to treat Kaposi's sarcoma in patients with immunodeficiency, whereas low doses are generally ineffective. Following low-dose recombinant interferon alfa treatment for lymphoma, two patients showed a regression of their hematologic malignancy-associated Kaposi's sarcoma. This observation prompted us also to try low-dose interferon alfa treatment in uncomplicated classic Kaposi's sarcoma, and two additional patients were thus treated on an outpatient basis. OBSERVATIONS: Initial response was noted after 3 to 13 weeks of treatment. Remission was achieved after 4 to 6 months of low-dose interferon alfa treatment and its duration was 8 to 14 months. Recurrences were treated again and additional remissions were obtained after only 5 to 8 weeks of treatment. CONCLUSION: Low-dose interferon alfa treatment may represent an effective therapeutic modality for the treatment of patients with both lymphoma-associated and uncomplicated classic Kaposi's sarcoma. PMID- 8215495 TI - Leukemia cutis in congenital leukemia. Analysis and review of the world literature with report of an additional case. AB - BACKGROUND: Congenital leukemia cutis is rarely reported in the dermatology literature despite various authors citing 50% of infants with congenital leukemia have skin involvement. These seemingly disparate facts prompted a review of the world literature that was performed by searching the MEDLINE database from 1966 up to and through December 1992, reviewing Index Medicus for the years prior to computerized MEDLINE search, and reviewing appropriate case report references. OBSERVATIONS: A 2-month premature male infant was born with 182 x 10(9)/L circulating monoblasts, prominent hepatosplenomegaly, and multiple firm blue and red cutaneous nodules. CONCLUSION: Approximately 175 cases of congenital leukemia have been reported with at least 41 and possibly 56 cases identified with leukemia cutis. Specific cutaneous leukemic infiltrates occur in 25% to 30% of infants with congenital leukemia and usually appear as firm blue, red, or purple nodules in a generalized distribution. In contrast to the 50% incidence of gingival and oral infiltrates reported in adult monocytic leukemia, only 1% of congenital leukemia patients have oral involvement. Congenital leukemia cutis may precede other manifestations of leukemia by as much as 4 months. Whereas leukemia cutis is associated with a poor prognosis in adult leukemics, the natural history of congenital leukemia is not altered by leukemia cutis. PMID- 8215496 TI - Pterygium inversum unguis. Report of 19 cases and review of the literature. AB - BACKGROUND: Pterygium inversum unguis is a rare abnormality of the nail bed that remains adherent to the ventral surface of the nail plate, resulting in a subungual extension of the hyponychium and obliteration of the distal groove. OBJECTIVE: The aim of our article is to illustrate the cases of pterygium inversum unguis that we observed in the last 20 years and to discuss them according to a broad review of the literature. RESULTS: Nineteen new cases of pterygium inversum unguis have been observed: one congenital idiopathic form, five acquired idiopathic forms, and 13 secondary forms. CONCLUSION: Our study and the review of the literature demonstrate that the most common forms of pterygium inversum unguis are the acquired secondary ones. They are generally related to systemic connective tissue diseases and, in particular, to progressive systemic sclerosis and systemic lupus erythematosus. PMID- 8215497 TI - Dermatosparaxis in children. A case report and review of the newly recognized phenotype. AB - BACKGROUND: Dermatosparaxis is an autosomal recessive connective tissue disorder in animals that is caused by abnormal processing of type I procollagen and results in skin laxity and fragility. Only three humans with characteristic biochemical and electronmicroscopic findings have been recognized to date. OBSERVATIONS: We describe the clinical and electronmicroscopic findings in an affected boy who presented at birth with large full-thickness groin fissures, micrognathia, large fontanelles, umbilical hernia, and dental laminal cysts. He subsequently exhibited marked skin fragility, blue sclerae, joint laxity, increased bruisability, and growth retardation. The diagnosis of dermatosparaxis was made by electron-microscopic findings consisting of characteristic small, irregular, and circular collagen fibers in the skin. His phenotype is strikingly similar to two other reported children with the disorder, which is now classified in humans as Ehlers-Danlos VII-C. CONCLUSIONS: The newly recognized phenotype of Ehlers-Danlos VII-C is a distinct connective tissue disorder characterized by marked skin fragility and laxity, blue sclerae, increased bruisability, micrognathia, umbilical hernia, and growth retardation. A suspected clinical diagnosis can be confirmed by electron-microscopic and biochemical studies of connective tissue. PMID- 8215498 TI - Ehlers-Danlos type VII-C, or human dermatosparaxis. The offspring of a union between basic and clinical research. PMID- 8215499 TI - Kaposi's sarcoma. Where do we go from here? PMID- 8215500 TI - Interface dermatitis. How specific are its histopathologic features? PMID- 8215501 TI - Psoriasis and cigarettes. Another nail in the coffin. PMID- 8215502 TI - Widespread erythematous scaly plaques in an adult. Psoriasiform eruption induced by quinidine. PMID- 8215503 TI - Multiple tender, erythematous subcutaneous nodules on the lower extremities. Membranous fat necrosis. PMID- 8215504 TI - Subcutaneous masses with multiple myeloma. Cutaneous extramedullary plasmacytoma. PMID- 8215505 TI - Poliosis in a scalp nodule. Congenital intradermal nevus with poliosis. PMID- 8215506 TI - The sensitivity and specificity of the potassium hydroxide smear. PMID- 8215507 TI - Sporotrichosislike infection caused by Mycobacterium avium in the acquired immunodeficiency syndrome. PMID- 8215508 TI - Hailey-Hailey disease of the vulva. PMID- 8215509 TI - Fissured tongue in generalized pustular psoriasis. PMID- 8215510 TI - Pityriasis rubra pilaris and cyclosporine. PMID- 8215511 TI - Metastatic Crohn's disease of the face: an uncommon presentation. PMID- 8215512 TI - Cysteine ameliorates photosensitivity in erythropoietic protoporphyria. PMID- 8215513 TI - Children First--the Audit Commission study of hospital services. PMID- 8215514 TI - Bone marrow transplantation for sickle cell disease. PMID- 8215515 TI - The value of urodynamic studies. PMID- 8215516 TI - Dietary management in nephrotic syndrome. PMID- 8215517 TI - How much wrapping do babies need at night? AB - In a longitudinal, population based study, overnight temperature recordings were made in the bedrooms of 152 babies aged 3-18 weeks and the insulation provided by their bedclothing was assessed. Outdoor temperatures for the study nights were also available. Parents applied more insulation on colder nights with lower bedroom temperatures than on warmer nights (mean 8.5 tog at 15 degrees C minimum bedroom temperature falling to 4.0 tog at 25 degrees C). For a particular temperature they also applied 2 tog more insulation in winter than in summer. The amounts of bedclothing used in the home were compared with insulation levels predicted to achieve thermo-neutrality over a similar range of environmental temperature from heat balance studies in young infants. They corresponded closely. The average amount of bedclothing chosen for babies in Avon allows them to remain in thermoneutral conditions throughout the night. These values are proposed as broad guidelines for the thermal care of young babies at night. PMID- 8215518 TI - Rebreathing expired gases from bedding: a cause of cot death? AB - The reported association of cot death and sleeping prone could be due to rebreathing of expired gases. A mechanical model simulating the respiratory system of an infant, exhaling warm humidified air with an end tidal carbon dioxide of 5%, has been used to investigate this. Some commonly used bedding materials caused an accumulation of carbon dioxide of 7% to over 10% with the model lying face down. This phenomenon persisted even with the head inclined at 45 degrees, but only on very soft materials, and could be a cause of cot death in a baby unresponsive to asphyxial blood gas changes. A coir fibre mattress allowed complete dispersal of exhalate as did a rubber sheet between any mattress and the covering sheet. PMID- 8215519 TI - Breathing abnormalities in sleep in achondroplasia. AB - Overnight sleep studies were performed in 20 subjects with achondroplasia to document further the respiratory abnormalities present in this group. Somatosensory evoked potentials (SEPs) were recorded in 19 of the subjects to screen for the presence of brainstem abnormalities, which are one of the potential aetiological mechanisms. Fifteen children aged 1 to 14 years, and five young adults, aged 20 to 31 years were included. All had upper airway obstruction and 15 (75%) had a pathological apnoea index (greater than five per hour). Other sleep associated respiratory abnormalities, including partial obstruction, central apnoea, and abnormal electromyographic activity of accessory muscles of respiration, also showed a high prevalence. SEPs were abnormal in eight (42%), but there was no correlation between abnormal SEPs and apnoea during sleep, either qualitatively or quantitatively. A high prevalence of both sleep related respiratory abnormalities and abnormal SEPs in young subjects with achondroplasia was demonstrated. However, the sleep related respiratory abnormalities do not always result in significant blood gas disturbances or correlate with abnormal SEPs in this group. PMID- 8215520 TI - Changes in nocturnal oximetry after treatment of exacerbations in cystic fibrosis. AB - Sleep related arterial oxygen desaturation has been described in clinically stable young adults with cystic fibrosis. The incidence and severity of nocturnal oxygen desaturation in children during infective exacerbations and the changes that occur with treatment were examined. Forty five children with proved cystic fibrosis, median age 8.9 years, admitted to the Regional Cystic Fibrosis Unit underwent clinical evaluation, spirometry, and measurement of peak flow and nocturnal oxygen saturation on admission and after 10 days' treatment. There was a significant improvement in all the above measurements, with the averaged overnight saturation changing from a mean (SD) 92.7 (2.7)% to 94.3 (2.0)%, mean (SE) difference 1.58 (0.37). The time spent with a saturation 4% or more below their clinic value showed a marked improvement from 122 (152) minutes on the first night to 21 (30.7) on the second, mean (SE) difference 101 (22.4). Eight young children could not perform pulmonary function tests, all desaturated on the admission night. Nocturnal hypoxaemia is a common finding in young cystic fibrosis patients during infective exacerbations but improves with treatment. Overnight oximetry is simple to perform, well tolerated, and identifies patients with marked nocturnal desaturation. PMID- 8215521 TI - Audit strategies to reduce hospital admissions for acute asthma. AB - An eightfold rise in hospital admissions for acute asthma from 1971-85 prompted two studies to audit the admissions policy at the Royal Alexandra Hospital. In the first study the on call senior house officer (SHO) was replaced by an experienced registrar and over a four month period 53 children out of 158 were sent home from the receiving room compared with six out of 39 seen by the SHOs. In the second study an SHO training programme was established together with a home treatment package. Over a 12 month period the on call SHOs assessed 687 children with acute asthma; 229 (43.5%) were deemed fit to be sent home. Only seven of these were readmitted within one week. Diary symptom score cards filled in by parents indicated that children sent home without admission fared no worse at home than those admitted and then discharged for the two weeks after leaving hospital. The development of strategies to improve assessment and immediate management in the hospital receiving room can reduce hospital admissions for acute asthma, allowing more children to be safely managed in the community. PMID- 8215522 TI - Comparison of the efficacy and safety of inhaled fluticasone propionate 200 micrograms/day with inhaled beclomethasone dipropionate 400 micrograms/day in mild and moderate asthma. AB - This study was designed to compare the efficacy and safety of a new inhaled corticosteroid, fluticasone propionate at a total daily dose of 200 micrograms, with beclomethasone dipropionate 400 micrograms/day in childhood asthma. A total of 398 asthmatic children (aged 4-19 years) were randomised to receive either fluticasone propionate 200 micrograms daily or beclomethasone dipropionate 400 micrograms daily for six weeks inhaled via a spacer device from a metered dose inhaler. During the study the patients recorded morning and evening peak expiratory flow rate (PEFR), symptom scores, and use of beta 2 agonist rescue medication. In addition, clinic visit PEFR and forced expiratory volume in one second were measured. Safety was assessed by recording all adverse events and by performing routine biochemistry and haematology screens including plasma cortisol concentration before and after treatment. For the purposes of analysis the diary card data were grouped into three periods: week 3 (days 15-21), week 6 (days 36 42), and weeks 1-6 (days 1-42). The results showed no significant difference between treatments on most efficacy parameters. However, there were significant differences in changes from baseline in favour of fluticasone propionate for % predicted morning PEFR both at week 3 (fluticasone propionate 6.1%, beclomethasone dipropionate 3.9%) and at week 6 (fluticasone propionate 8.3%, beclomethasone dipropionate 5. 9%) and % predicted evening PEFR at week 6 (fluticasone propionate 7.3%, beclomethasone dipropionate 4.9% and over weeks 1-6 (fluticasone propionate 5.5%, beclomethasone dipropionate 3.6%. Comparison between groups showed that the group receiving fluticasone propionate had a lower % of days with symptom-free exercise at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 81%) and % days without rescue medication at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 80%) and over weeks 1-6 (fluticasone propionate 80%, beclomethasone dipropionate 73%). Except for a higher incidence of sore throat in the fluticasone propionate group, the two treatments did not differ with regard to safety. There was no evidence of adrenal suppression with either treatment. In conclusion, fluticasone propionate 200 microgram daily ws at least as effective and as well tolerated as beclomethasone dipropionate 400 microgram daily in childhood asthma. PMID- 8215523 TI - Glycine site of the excitatory amino acid N-methyl-D-aspartate receptor in neonatal and adult brain. AB - The N-methyl-D-aspartate (NMDA) receptor complex in brain is a glutamate receptor subtype with several recognition sites including a glycine site that is able to modulate and activate allosterically the receptor. This receptor may be important in the regulation of developmental synaptic plasticity. The release of glutamate and consequent overstimulation of NMDA receptors that follows hypoxia-ischaemia leads to brain damage. Brain tissue obtained at necropsy was studied in a total of 16 term infants aged less than 1 week to 22 weeks and in four adults aged from 66 to 84 years. Glycine sites were determined in brain sections by the binding of the selective ligand [3H]5,7-dichloro-kynurenic acid and measured by autoradiography. In infant brains the amount of binding to the glycine site was higher in temporal cortex and hippocampus than in basal ganglia and was also higher than in comparable areas of adult brain. The amount of glycine site binding in infant cortex increased with postnatal age. The data suggest that infant brain acquires a relatively high density of NMDA receptors in temporal lobe due to postnatal proliferation of glutamatergic synapses. These findings have therapeutic implications as drugs that reduce NMDA receptor function by blocking the glycine modulatory site would be pertinent to preventing brain damage after hypoxia-ischaemia. PMID- 8215524 TI - Right heart pressure determination by Doppler in infants with tricuspid regurgitation. AB - Doppler and direct measurements of right ventricle to right atrial pressure drop were made during cardiac catheterisation on 28 occasions in 26 infants with congenital heart disease. Age was 10 days to 12 months (median 4.5 months), and weight was 3.1 to 9.0 kg (median 4.7 kg). We measured peak velocity of tricuspid regurgitation by continuous wave Doppler, and the pressure drop was calculated using the modified Bernoulli equation (delta p = 4v2). There was a high correlation (r = 0.95) between direct and Doppler measurements. Doppler values tended to underestimate the right ventricle to right atrial pressure drop, but this was not of clinical significance (mean 2 mm Hg). The 95% confidence interval for the Doppler velocity was -0.41 to +0.26 m/sec, and was consistent across the range of pressures studied. Variability between observers was tested, by two observers performing sequential paired examinations on 16 newborn babies with tricuspid regurgitation. The coefficient of repeatability was 6.3 mm Hg (95% confidence interval 4.7 to 9.5 mm Hg) or 0.26 m/sec (0.18 to 0.50 m/sec). This method of right ventricular pressure estimation, validated previously only in older children and adults, is a reproducible and accurate technique in infants with tricuspid regurgitation. PMID- 8215525 TI - Prolonged carriage of Clostridium difficile in Hirschsprung's disease. AB - The role of Clostridium difficile in the aetiology of diarrhoea in children with Hirschsprung's disease was investigated in a prospective longitudinal study. In 64 children with Hirschsprung's disease no significant difference was found in the isolation rate of C difficile in patients with diarrhoea (32%) and without diarrhoea (26%). Comparable isolation rates were found in 47 control children with and without diarrhoea (27% and 16% respectively). The number of strains producing toxin B was similar in the four groups of children. In contrast to the disappearance of C difficile by 12 months of age in the control groups of children, C difficile could be repeatedly isolated from a proportion of children with Hirschsprung's disease over 12 months of age. These findings help to reconcile the existing contradictory reports on the incidence of C difficile in Hirschsprung's disease associated enterocolitis. PMID- 8215526 TI - Invasive Haemophilus influenzae type b disease in the Oxford region (1985-91). AB - For a seven year period (1985-91) clinical and epidemiological data were prospectively collected on children aged < 10 years with microbiologically confirmed invasive Haemophilus influenzae type b infection in the Oxford region to study the epidemiology of the disease and determine the potential impact of early primary immunisation in infants. Computer records of primary immunisations given to these cases were retrospectively analysed and, where necessary, hospital and general practitioner records were searched to determine the immunisation history. Over the seven year period, 416 cases of invasive H influenzae type b disease were reported. Widescale immunisation against H influenzae type b began in 1991 as part of a regional trial. The estimated annual incidence for invasive disease between 1985 and 1990 was 35.5 cases per 100,000 children aged less than 5 years; for H influenzae type b meningitis it was 25.1 per 100,000 children aged less than 5 years. The cumulative risks for invasive disease and meningitis by the fifth birthday were one in 560 and one in 800 respectively. The majority of disease (71%) occurred in children less than 2 years of age with the peak monthly incidences at 6 and 7 months of age. The overall mortality was 4.3% and 50% of these deaths occurred suddenly. Most (91%) of the children had received at least one primary immunisation against diphtheria, tetanus, and pertussis before H influenzae type b infection and there was only one case of parental refusal of immunisation. None had received H influenzae type b immunisation. Given a vaccine uptake of 90% by 5 months of age it is estimated that at least 82% of the H influenzae type b infections could have been prevented. Extrapolated nationally, 1150 cases of infection and 50 deaths could be prevented each year by routine primary immunisation. PMID- 8215527 TI - Mycobacterial infection in an inner city children's hospital. AB - Childhood tuberculosis is perceived by many as a disease of the past. Experience in a children's hospital serving a deprived population suggested that tuberculosis and other mycobacterial infections were not declining in clinical practice. Fifty three tuberculous and 11 atypical mycobacterial infections were identified between 1978 and 1992. There was no decline in tuberculosis and nine of the 11 atypical infections occurred in the last five years. Altogether 40% of cases of tuberculosis were in non-Asian children; 32% had arrived in the UK or visited family overseas in the previous year; and 38% had a history of tuberculosis contact, usually a close adult relative. Nationally, the previous decline in tuberculosis in all ages has reversed. In the local health districts in London's east end, childhood tuberculosis has also stopped declining and seems to be increasing. It is regrettable that BCG vaccination has been abolished by some districts in the UK, against current recommendations. Childhood tuberculosis is still common in the practice described here, including among children who do not fall into conventionally recognised high risk groups. Inner city dwellers and junior doctors are both highly mobile populations, adding to the risk that paediatricians, particularly those in training, may encounter tuberculosis with little or no previous experience of the condition. PMID- 8215528 TI - Correlation of serum neopterin concentrations with disease activity in juvenile dermatomyositis. AB - Serum neopterin concentrations were measured in 15 patients with juvenile dermatomyositis and their correlation with the severity of muscle impairment was evaluated. Neopterin concentrations were measured by radioimmunoassay. When compared with controls (median 0.75 ng/ml; range 0.33-1.18), serum neopterin concentrations were increased in patients with active juvenile dermatomyositis (median 3.21 ng/ml; range 0.95-13.81), but not in patients during remission (median 0.81 ng/ml; range 0.55-1.34). In horizontal and longitudinal studies, serum neopterin was significantly correlated with the severity of muscle strength impairment, whereas serum muscle enzyme values were not. These data suggest that measurement of serum neopterin may be used, together with clinical examination, to guide the treatment of patients with juvenile dermatomyositis. PMID- 8215529 TI - Immunoadsorption plasmapheresis for severe generalised myasthenia gravis. AB - Two patients with severe generalised myasthenia gravis of childhood were successfully treated with immunoadsorption plasmapheresis. One patient was a 5 year old girl and the other was a 12 year old girl. A dramatic improvement in bulbar symptoms and generalised muscle weakness was achieved without any side effects. Plasma exchange may also yield clinical improvement for myasthenia gravis, but the treatment is accompanied by the risk of viral infections and hypersensitivity reactions. Immunoadsorption plasmapheresis is an effective treatment for severe generalised myasthenia gravis of childhood and is superior to plasma exchange with respect to safety. PMID- 8215530 TI - Clostridium difficile after haemolytic uraemic syndrome. AB - Six children are described who developed diarrhoea associated with Clostridium difficile during the course of haemolytic uraemic syndrome. The significance of this infection is discussed within the context of the pathophysiology of haemolytic uraemic syndrome. PMID- 8215531 TI - Aneurysmal cyst of the petrosal bone. AB - An aneurysmal cyst of the petrosal bone presenting as hearing loss and recurrent bacterial meningitis is reported. None of the clinical or radiographic signs described previously were present. Because other diagnostic methods are not reliable, it is recommended that coronal thin section computed tomography be performed in every case of suspected malformation of the skull base and in the diagnosis of recurrent bacterial meningitis. PMID- 8215532 TI - Hepatic abscess in sickle cell anaemia: a rare manifestation. AB - A child with sickle cell anaemia developed a hepatic abscess, which was managed successfully by percutaneous drainage under ultrasound control. A history of attacks of pain dissimilar to usual vaso-occlusive crises should be treated with suspicion and investigated appropriately. PMID- 8215533 TI - Group psychotherapy for children and adolescents. PMID- 8215534 TI - Paediatrics in The Netherlands: challenges for today and tomorrow. PMID- 8215535 TI - Data transformations. PMID- 8215536 TI - Acquired protein S deficiency. PMID- 8215537 TI - Do paediatricians use problem lists when writing to general practitioners? PMID- 8215538 TI - Snoring, sleep disturbance, and behavior in 4-5 year olds. PMID- 8215539 TI - MRCP (UK) Part 1 examination: new arrangements. PMID- 8215540 TI - Recent advances in paediatric neurosurgery. PMID- 8215541 TI - Body composition assessment. PMID- 8215542 TI - Galactosaemia: results of the British Paediatric Surveillance Unit Study, 1988 90. AB - Ascertainment of cases of classical galactosaemia over a three year period in the UK and the Republic of Ireland, through the British Paediatric Surveillance Unit, identified 58 proved cases and two in whom the diagnosis was strongly suspected. One patient died at 4 days, and severe morbidity was no more frequent in babies diagnosed clinically because of their symptoms compared with those who were screened for galactosaemia. Treatment of four babies in the non-screened group was delayed until after 5 weeks of age, but it is concluded that all cases of galactosaemia could be diagnosed in an acceptable time without screening, providing clinical vigilance is maintained. PMID- 8215543 TI - Normal gastric antral myoelectrical activity in early onset anorexia nervosa. AB - Anorexia, epigastric discomfort, nausea, and vomiting may result from disordered gastric motility and emptying. These features have been found in many adults with anorexia nervosa, but have never been investigated in early onset anorexia nervosa. In 14 patients with early onset anorexia nervosa (eight of whom had upper gastrointestinal tract symptoms), six children with other eating disorders, four children with non-ulcer dyspepsia, and 10 controls matched for age and sex, the non-invasive technique of surface electrogastrography was used to measure fasting and postprandial gastric antral electrical control activity, which underlies antral motility. The electrical signal was recorded by four bipolar silver/silver chloride electrodes attached to the upper abdomen, amplified and low pass filtered at 0.33 Hz before being displayed on a polygraph, digitised at 1 Hz, and stored on the hard disk of a personal computer for later offline analysis. Patients with non-ulcer dyspepsia had gastric antral dysrhythmias. No significant difference was found in the mean (SD) dominant frequency of the antral electrical control activity between patients with early onset anorexia nervosa (2.86 (0.35) cycles/minute (cpm)), patients with other eating disorders (3.14 (0.65) cpm), and controls (3.00 (0.46) cpm). The amplitude of electrical control activity increased postprandially in all but one subject and the fasting/postprandial amplitude ratio did not significantly differ between patients with early onset anorexia nervosa and controls, though patients with longer established disease had a smaller increase in amplitude. Gastric antral electrical dysrhythmias are not a feature of early onset anorexia nervosa and therefore do not induce or perpetuate food refusal in this disorder. PMID- 8215544 TI - Radiological assessment of the atlantoaxial distance in Down's syndrome. AB - People with Down's syndrome are pre-disposed to atlantoaxial instability. As part of a study to determine whether those with Down's syndrome should be screened for atlantoaxial instability before they participate in sport, a series of 279 children, aged 6 to 17 years was investigated radiologically. Lateral radiographs of the cervical spine were taken in neutral position and in flexion. The magnification factor was assessed by means of a marker attached to the nape of the neck. After correction for magnification 15% of the patients were found to have an atlantoaxial distance greater than 4 mm on the flexion film, especially boys under 11 years of age. However, sex and age together explained at most 9% of the variation in atlantoaxial distance. The maximum distance found was 6.5 mm. The disagreement between the means of first and second measurements by the same (test-retest) and by another (inter-) observer was more for those taken in the neutral position than in flexion. On a group level the results for reliability were satisfactory. PMID- 8215545 TI - Use of budesonide in severe asthmatics aged 1-3 years. AB - The treatment of severe asthmatics aged 1-3 years with budesonide administered via Nebuhaler and Laerdal facemask was assessed in a six month, double blind, placebo controlled study. Patients were randomised to budesonide (n = 20) or placebo (n = 20) treatment. Daily symptom scores were recorded by parents and clinic visits occurred every six weeks. Cough scores improved significantly with budesonide: nocturnal and daytime cough scores (0-2) fell by a mean (SEM) of 0.4 (0.2) and 0.5 (0.2); while with placebo the nocturnal score increased by 0.1 (0.2) and daytime score was unchanged at 0.0 (0.2). All other data showed improvements for active over placebo treatment. Thirteen children in each group completed six months' treatment. Parents of 25 of these found the delivery system convenient and easy to use. While blinded to treatment it was assessed to be beneficial in nine of 13 receiving budesonide and four of 13 receiving placebo. The Nebuhaler and facemask is an acceptable delivery system for long term asthma treatment. Symptoms are significantly reduced when it is used to give 400-800 micrograms budesonide/day to children aged 1-3 years who cannot use other delivery systems. PMID- 8215546 TI - Deaths from volatile substance abuse in those under 18 years: results from a national epidemiological study. AB - The epidemiology of deaths from volatile substance abuse (VSA) in those under 18 years that occurred in the UK from 1981-90 is described. The analysis of deaths is based on a national register, which has information obtained from a regular survey of coroners, the Office of Population Censuses and Surveys, and a press clippings agency. Altogether 605 people under 18 died from VSA during this period. Seventy per cent of deaths occurred between the ages of 14 and 16. The largest number of deaths were attributed to butane gas lighter refills. There was a large north-south gradient in age specific mortality ratios (Scotland 180, south east England 87) and nearly four times as many deaths occurred in social class V compared with social class I. Deaths from VSA are an important and preventable cause of deaths in those under 18. Strategies aimed at prevention should include measures to reduce experimentation, intervention to reduce socioeconomic deprivation, and health education campaigns aimed at schools and parents. PMID- 8215547 TI - Measurement of fat digestion in early life using a stable isotope breath test. AB - 13C breath tests are a safe, non-invasive way of assessing nutrient digestion and absorption that can be used repeatedly in infancy and childhood. The aim of this study was to assess their value for measuring fat digestion in infants and young children with cystic fibrosis, and healthy controls whose pancreatic exocrine function is immature, and to monitor pancreatic enzyme supplementation. Six infants with cystic fibrosis (aged 10-18 months) and nine healthy controls (aged 6-19 months) were studied. After an overnight fast each child ingested 7.5 mg/kg 13C trioctanoin (99 atom % excess) followed by a known volume of milk. Breath samples were collected before and at 30 minute intervals thereafter for five hours. The 13C enrichment of expired carbon dioxide was measured by gas isotope ratio mass spectrometry. The mean (SD) percentage dose recovery of 13C was 13.5 (5.3) for the cystic fibrosis group and 24.2 (6.7) for the healthy controls. When those with cystic fibrosis were studied after supplementary pancreatic enzymes, the mean percentage dose recovery rose to 17.1 (6.9). Total intraluminal lipolysis was diminished by 44% in young children with cystic fibrosis. Pancreatic enzyme supplements improved digestion by 27%. The 13C trioctanoin breath test was effective in detecting fat maldigestion and can be used to measure the benefits of enzyme supplements in early life. PMID- 8215548 TI - Tuberculosis in infants less than 3 months of age. AB - The clinical and radiological features in 38 infants less than 3 months of age with tuberculosis proved by culture are described and may aid early diagnosis of this often fatal condition. Respiratory symptoms, cough in 33 (87%) and tachypnoea in 31 (82%), were the commonest presenting symptoms. Twenty five infants (66%) had hepatomegaly and 20 (53%) splenomegaly. Mantoux testing gave an induration of > 15 mm in three of 17 (18%) infants. In a further five a Tine test gave confluent response. Chest radiography in 27 infants showed miliary tuberculosis in seven (26%) and hilar or paratracheal adenopathy in 14 (52%) and 10 (37%) respectively. Compression of either the bronchi or trachea or both was noted in 15 (56%). Detection of this complication was aided by high kilovolt radiographs. A culture of Mycobacterium tuberculosis was obtained from gastric aspirate in 35 (92%) infants, but positive cultures were also obtained from cerebrospinal fluid, tracheal or bronchial aspirate and liver and lymph node biopsy. Of 30 mothers evaluated seven (23) had previously unsuspected pulmonary tuberculosis. PMID- 8215549 TI - Different features of coeliac disease in two neighbouring countries. AB - Against the background of reported different trends of incidence and presentation of coeliac disease in Sweden and Finland, a joint study was done to explore potential causes. The clinical study confirmed that classical symptoms and diagnosis before 2 years of age dominated in Sweden. In Finland, the symptoms were more diffuse and diagnosis in most cases was made after the age of 8 years. A significantly lower weight score attained at diagnosis was seen in Swedish patients compared with Finnish. No significant difference in HLA expression was found. Infant feeding was investigated by studying food records of healthy infants. Swedish infants ingested three times more wheat protein at 9 months and twice as much at 12 months compared with Finnish children. It is concluded that the intake of infant cereal protein might influence when and how clinical coeliac disease appears. The question whether or not it is important for if coeliac disease will be acquired still remains to be answered. PMID- 8215550 TI - Overwhelming sepsis presenting as sudden unexpected death. AB - Four children, including three infants, who died suddenly and unexpectedly are described. In three of the cases group A beta haemolytic streptococcus was cultured and in the fourth Streptococcus pneumoniae. The organism was grown from multiple sites including blood in two of them. Without microbiological investigation the diagnosis would have been sudden unexpected death syndrome. PMID- 8215551 TI - Spermaturia and puberty. AB - The pattern of spermaturia in boys at different stages of puberty was investigated. Fractionated 24 hour urine was collected for nine consecutive days from eight boys aged 13-14 years and 10 boys aged 15-17 years. Spermatozoa were detected by microscopic examination of the sediment. Sex characteristics were recorded. Fifty five per cent of all urine samples were positive for sperm and all boys showed spermaturia. A large variation in spermaturia was found between and within boys at the same stage of puberty. Spermaturia was a more common and regular event during early and mid-puberty than in more mature subjects. This indicates that the mechanism of spermaturia in early and late puberty could be different. It is suggested that spermaturia in non-virilised boys could be a result of a spontaneous, continuous flow of spermatozoa to the urethra in contrast with the peristaltic flow during ejaculation occurring at a later stage of puberty. PMID- 8215552 TI - Effect of sucrose on crying in response to heel stab. AB - It has been suggested that sucrose acts as an analgesic in the neonatal period. To evaluate this further, 52 infants received either 2 ml of 7.5% sucrose or 2 ml of sterile water before heel stab blood sampling. The duration of crying in response to sampling did not differ in the two groups but was related to level of arousal at the time of stimulation. PMID- 8215553 TI - Magnetic resonance imaging in tracheal compression by the innominate artery. AB - Tracheal compression by the innominate artery is frequently suspected in infants with noisy breathing and no obvious aortic arch anomalies or pulmonary artery sling. However the diagnosis is difficult to confirm. The findings after using magnetic resonance imaging in two infants with tracheal compression syndrome are presented. PMID- 8215554 TI - Near fatal ingestion of oil of cloves. AB - A case of ingestion of oil of cloves is presented, which resulted in coma, fits, a coagulopathy, and acute liver damage. This is not unlike the syndrome produced in the late stages of a substantial paracetamol overdose, and a similar treatment regimen is proposed. PMID- 8215555 TI - Child health surveillance for psychiatric disorder: practical guidelines. PMID- 8215556 TI - Physically handicapped school leavers. PMID- 8215557 TI - Management of mucopolysaccharidosis type III. PMID- 8215558 TI - Liver cirrhosis in cystic fibrosis. PMID- 8215559 TI - Hair loss in children. PMID- 8215560 TI - Chicken scratches. PMID- 8215561 TI - Surgical management of neonatal necrotising enterocolitis. PMID- 8215562 TI - Doppler and fetal growth retardation. PMID- 8215563 TI - Role of erythropoietin in the newborn. PMID- 8215564 TI - Multicentre randomised trial comparing high and low dose surfactant regimens for the treatment of respiratory distress syndrome (the Curosurf 4 trial). AB - A randomised trial was conducted in 82 centres using the porcine surfactant extract, Curosurf, to compare two regimens of multiple doses to treat infants with respiratory distress syndrome and arterial to alveolar oxygen tension ratio < 0.22. Infants were randomly allocated to a low dosage group (100 mg/kg initially, with two further doses at 12 and 24 hours to a maximum cumulative total of 300 mg/kg; n = 1069) or a high dosage group (200 mg/kg initially with up to four further doses of 100 mg/kg to a maximum cumulative total of 600 mg/kg; n = 1099). There was no difference between those allocated low and high dosage in the rates of death or oxygen dependency at 28 days (51.1% v 50.8%; difference 0.3%, 95% confidence interval (CI) -4.6% to 3.9%), death before discharge (25.0% v 23.5%; difference -1.5%, 95% CI -5.1% to 2.2%), and death or oxygen dependency at the expected date of delivery (32.2% v 31.0%; difference -1.2%, 95% CI -5.2% to 2.7%). For 14 predefined secondary measures of clinical outcome there were no significant differences between the groups but the comparison of duration of supplemental oxygen > 40% did attain significance; 48.4% of babies in the low dose group needed > 40% oxygen after three days compared with 42.6% of those in the high dose group. The total amount of surfactant administered in the low dose regimen (mean 242 mg phospholipid/kg) was probably enough to replace the entire pulmonary surfactant pool. Adopting the low dose regimen would lead to considerable cost savings, with no clinically significant loss in efficacy. PMID- 8215565 TI - Early or late parenteral nutrition for the sick preterm infant? AB - No one doubts that good nutrition is an important component of neonatal intensive care, nor that this can only be accomplished by the use of intravenous fat. With regard to the effects of nutrition on bronchopulmonary dysplasia, however, we are facing a dilemma. On the one hand there is the suggestion that inadequate nutrition increases the severity of bronchopulmonary dysplasia and on the other that the use of intravenous fat predisposes to it. In an attempt to narrow the area of uncertainty we randomly allocated 129 infants of less than 1750 g birth weight to receive either early or late lipid containing parenteral nutrition. The median duration of ventilation support in the 'early' group was 8.5 days and in the 'late' group eight days; this was not significantly different. PMID- 8215566 TI - Randomised controlled trial of plasma protein fraction versus dopamine in hypotensive very low birthweight infants. AB - Around 20% of very low birthweight infants admitted to a neonatal intensive care unit become hypotensive within 24 hours of their admission. Standard treatment is either expansion of the circulating volume by the infusion of plasma protein fraction or by using dopamine to improve cardiac function. The purpose of this study was to investigate by a randomised controlled trial which was the most appropriate treatment. Thirty nine infants were randomised to receive either plasma protein fraction or dopamine as first line treatment if they became hypotensive within 24 hours of admission to the neonatal intensive care unit. Seventeen of 19 (89%) infants responded to dopamine, whereas only 9/20 (45%) responded to plasma protein fraction. The median dose of dopamine needed to increase the blood pressure to at least the 10th centile was 7.5 micrograms/kg/min and was infused for a median duration of 18 hours. These observations suggest that dopamine should be used earlier in the treatment of these infants than has previously been recommended. PMID- 8215567 TI - Malformations, withdrawal manifestations, and hypoglycaemia after exposure to valproate in utero. AB - An unselected series is presented of 17 infants born to epileptic mothers and exposed to sodium valproate during pregnancy. Nine infants had minor abnormalities and of these infants five also had major malformations, described as the 'fetal valproate syndrome'. The most frequent malformation was congenital heart disease. Nine of the infants had manifestations of withdrawal, such as irritability, jitteriness, abnormalities of tone, seizures, and feeding problems. Four of these infants had an unrelated hypoglycaemia. The frequency of withdrawal symptoms was significantly related to the dose of valproate given to the mothers in the third trimester, and there was a tendency for both the frequency of the minor abnormalities and the major malformations to be related to the valproate dosage in the first trimester. PMID- 8215568 TI - Neonatal symptoms in medium chain acyl coenzyme A dehydrogenase deficiency. AB - Medium chain acyl coenzyme A dehydrogenase (MCAD) deficiency has not been thought to be associated with significant neonatal symptoms. To determine the validity of this, all known MCAD cases from New South Wales were reassessed. A total of 16 confirmed and three presumed cases has been identified in New South Wales, from 15 families. The casenotes of patients were reviewed, and where possible the mothers interviewed, either directly or by telephone, to obtain information about neonatal events. Six of the 16 confirmed cases had significant neonatal symptoms, with onset from 17 hours to 3 days of age. All required intravenous dextrose and four of the six needed other interventions, including hospital transfer. One baby died. All six were breast fed, but so were five of the eight asymptomatic neonates for whom information was available. Four of the six symptomatic neonates were homozygous for the common MCAD mutation, an A to G transition at position 985, and one was heterozygous. It is concluded that serious neonatal symptoms are common in MCAD. Newborn siblings of MCAD cases must have careful monitoring and support during the first few days of life. PMID- 8215569 TI - Annual audit of three year outcome in very low birthweight infants. AB - Annual odds ratios, standardised for known confounding variables, were used to examine trends in outcome at 3 years of age among 1499 infants of less than 1500 g birth weight admitted to a regional referral centre between 1980 and 1989. Despite improved survival, the chance of survival with a major disability or with cerebral palsy was unchanged. The likelihood of dying or surviving with a major disability significantly reduced during the decade. PMID- 8215570 TI - Urinary saturation and nephrocalcinosis in preterm infants: effect of parenteral nutrition. AB - Urinary lithogenic and inhibitory factors were studied in 27 preterm infants; 16 had total parenteral nutrition (TPN) and 11 had breastmilk with an additional glucose-sodium chloride infusion. Urines were collected for 24 hours on day 2 (period A), day 3 (B), and once between days 4 and 10 (C). Urinary calcium oxalate saturation was calculated by the computer program EQUIL 2. Renal ultrasonography was performed every second week until discharge. The calcium/creatinine ratio increased in infants on TPN (A 0.91; C 1.68 mol/mol) and was significantly higher at period C than that in infants on breastmilk/infusion (A 0.52; C 0.36). The oxalate/creatinine ratio was persistently higher with TPN (203 mmol/mol) than with breastmilk/infusion (98; 137). The citrate/creatinine remained constant with TPN (0.44 mol/mol), whereas it increased significantly with breastmilk/infusion (0.26; 0.49). Calcium/citrate rose considerably with TPN, but decreased with breastmilk/infusion to a significantly lower level than with TPN. The urinary calcium oxalate saturation increased with TPN (2.4; 4.5) and decreased with breastmilk/infusion (2.1; 1.5) to a significantly lower value than with TPN. Nephrocalcinosis developed in two infants on TPN. Mean daily calcium intake was similar in both groups, whereas protein, sodium, and phosphorus intake were significantly higher on TPN. It is concluded that the increase in urinary calcium oxalate saturation observed with TPN is due to the combined effect of an increased urinary calcium excretion and higher urinary oxalate/creatinine and calcium/citrate ratios. The changes observed are likely to be caused by TPN itself, which differs in several respects from breastmilk feeding. PMID- 8215571 TI - Neonatal cerebral blood flow velocity responses to changes in posture. AB - Maintaining a constant cerebral blood flow during a change in cerebral perfusion pressure is known as autoregulation. The integrity of this phenomenon is considered to be important in preventing cerebral lesions in preterm infants. A study was carried out using Doppler ultrasound measurements of cerebral blood flow velocities (CBFV) as an indicator of alterations in cerebral haemodynamics. CBFV were recorded on a beat to beat basis over 60 second epochs, during which time the cerebral perfusion pressure was changed by rapidly altering the infants' posture from horizontal to either 20 degrees head up or head down. An informative response in CBFV was considered to be either (a) a uniphasic, immediate, passive alteration in velocity occurring with the change in posture and without a subsequent change or (b) a biphasic response of an initial change in CBFV followed within 20 seconds by a second response. This latter response is considered to be consistent with autoregulatory activity. A total of 501 epochs in 60 neonates of gestational age 24-41 weeks was analysed. It was shown that any one infant can make either response, but the reliability of making an active, biphasic response increases with increasing gestational age. PMID- 8215572 TI - Tuberculin response in preterm infants after BCG vaccination at birth. AB - A total of 101 preterm infants between 26 and 37 weeks' gestation who received BCG vaccination at birth were evaluated between two and four months after vaccination. Altogether 32% of these infants had no visible BCG scar. All infants were then tested with tuberculin purified protein derivative (PPD) but only 70 returned for the test to be read 48-72 hours later. The test was negative in 22 (31%) and there was an induration of < or = 5 mm in another 26 (37%) of the infants. Of 22 infants with no BCG scar, 19 (86%) had an induration of < or = 5 mm. In infants with a positive BCG scar a significantly higher number had an induration of PPD > 5 mm. There were no significant differences between the rate of scarring and tuberculin conversion in the infants born before or after 32 weeks' gestation. It is considered that routine BCG vaccination at birth on preterm infants is not indicated until a much larger study has been performed. PMID- 8215573 TI - Skin disinfection in preterm infants. AB - Greater care and a more thorough approach to intravenous catheter site disinfection may be important for the prevention of catheter related sepsis, especially with coagulase negative staphylocci in preterm infants. The efficacy of skin disinfection was evaluated in preterm infants using a skin swabbing technique after disinfectant exposure. In the first part of the study, 25 peripheral intravascular catheter sites were quantitatively sampled immediately after routine cannula insertion. Bacterial counts greater than 100 colony forming units/cm2 were observed from 10 (40%) sites. In the second part, sampling for bacterial colony counts was done after skin cleansing with various durations of exposure of chlorhexidine/alcohol swabs or povidone iodine. The overall mean reduction in bacterial colony counts after skin cleansing ranged from 90-99%. Skin sterilisation was achieved in 33-92% of cases. The use of two consecutive 10 second exposures resulted in a significantly improved reduction in colony counts compared with a single 10 second wipe. A longer 30 second exposure also resulted in a greater reduction of bacterial numbers compared with a shorter duration of 5 or 10 seconds. Repopulation of disinfected sites occurred within 48 hours. This effect was delayed by occluding the cleansed site with a semipermeable dressing. There were no significant differences between povidone iodine and the chlorhexidine swabs in reducing bacterial numbers. This study has demonstrated that a brief exposure with a premoistened disinfectant swab is not sufficient for complete elimination of resident skin flora of newborn infants. The use of two consecutive cleanings, or a longer duration of cleansing is recommended for more effective skin sterilisation. PMID- 8215574 TI - Pneumococcal infection in the newborn. AB - Two fatal cases of invasive pneumococcal disease in the newborn are reported, both acquired from the maternal vagina. The rarity of vaginal carriage of pneumococcus suggests that this organism has a higher invasion to colonisation ratio than group B streptococcus and maternal carriage or neonatal colonisation should be more aggressively treated. PMID- 8215575 TI - Self limiting neonatal primary hyperparathyroidism associated with familial hypocalciuric hypercalcaemia. AB - A boy is described who presented aged 7 weeks with severe biochemical and radiological neonatal hyperparathyroidism that had completely resolved by the age of 6 months. His mother had a normal serum calcium concentration but his father, paternal aunt, and paternal cousin all had a raised serum calcium due to familial hypocalciuric hypercalcaemia. PMID- 8215576 TI - How have recent changes in the NHS affected perinatal audit? PMID- 8215577 TI - Dr Thomas Radford (1793-1881) of Manchester and obstructed labour. PMID- 8215578 TI - Neonatal respiratory distress syndrome. PMID- 8215579 TI - Varicella zoster virus infection in pregnancy. PMID- 8215580 TI - The effectiveness and side effects of dexamethasone in preterm infants with bronchopulmonary dysplasia. PMID- 8215581 TI - A novel antigen of the dermal-epidermal junction defined by an anti-CD1b monoclonal antibody (NU-T2). AB - NU-T2 is a mouse monoclonal IgG1 antibody to the CD1b molecule, (cross-)reacting with an antigen of the dermal-epidermal junction (NU-T2 DEJ AG). Further immunohistochemical characterization of the NU-T2 DEJ AG showed it to display unique properties that differentiate it from other known antigens of the dermal epidermal junction. Indeed, the NU-T2 DEJ AG is primate-specific and present only in epithelial basement membranes. In normal human skin it is expressed within the lowermost lamina lucida of the dermal-epidermal junction but not in the deep part of epidermal appendages nor in the deep part of epidermal appendages nor in the basement membrane of dermal vessels, smooth muscles or nerves. In diseases with intraepidermal or intradermal cleavage, NU-T2 reactivity was observed at the floor of the blister. In various skin specimens with a cleavage through the lamina lucida (NaCl--or dispase-split skin, bullous pemphigoid, junctional epidermolysis bullosa), NU-T2 immunoreactivity seemed reduced, being localized at the dermal side of the cleavage. These results suggest that the antigen recognized by NU-T2 is a novel component of the lamina lucida of the dermal epidermal junction, that seems to be important for dermal-epidermal adhesion. PMID- 8215582 TI - Serum markers of collagen synthesis and degradation in skin diseases. Altered levels in diseases with systemic manifestation and during systemic glucocorticoid treatment. AB - Serum concentrations of the markers of collagen synthesis and degradation, collagen I propeptide (PICP), collagen III propeptide (PIIINP) and the cross linked telopeptide of type I collagen (ICTP) were measured in young male dermatological patients and in control subjects. No significant differences were noted between patients suffering from atopic eczema (n = 24), other eczemas (n = 11), acne (n = 8), psoriasis (n = 7) or tinea (n = 9) and the control subjects (n = 24). In the total study population representing patients with common skin diseases and control subjects there was a significant correlation between the serum concentrations of PICP and PIIINP and between the concentrations of PICP and ICTP. This suggests that synthesis of type I and III collagens in vivo is coordinated and that the degradation and synthesis of type I collagen is balanced. These markers were also measured in older patients suffering from psoriasis, eczema and various connective tissue diseases. It was noted that the degree of skin involvement in these diseases was not related to the serum concentrations of the markers of collagen metabolism. The highest levels of PICP and PIIINP were observed in a patient with systemic mastocytosis (PICP 309 micrograms/l and PIIINP 8.0 micrograms/l). Increased levels of PIIINP were also found in patients with a high alcohol consumption. We have previously demonstrated that systemic glucocorticoids reduce collagen propeptide levels in serum. In the present study we also proved that systemic glucocorticoids have no effect on collagen degradation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215583 TI - In situ hybridization analysis of cytokine, proto-oncogene and tumour suppressor gene expression in psoriasis. AB - The purpose of this study was to investigate and to compare, by in situ hybridization, gene expression of IL-1 beta, IL-8, TGF-beta 1, TGF-beta 2, TGF beta 3, TGF-alpha, p53 and c-myc in lesions and in non-involved skin of patients with psoriasis. All lesional skin biopsies showed overexpression of IL-1 beta, IL 8 TGF-alpha mRNAs. IL-1 beta hybridization signals were strong in a small number of cells localized predominantly in the dermal papillae and in the suprapapillary epidermis. Overexpression of TGF-alpha was observed in all suprabasal keratinocytes, whereas strongly elevated IL-8 mRNA expression was found to be restricted to clusters of suprabasal keratinocytes. TGF-beta 3, p53 and c-myc transcripts were clearly detected in the epidermis of all biopsies, although expression levels were comparable in lesional and non-lesional skin. PMID- 8215584 TI - The effect of reactive oxygen species on the biosynthesis of collagen and glycosaminoglycans in cultured human dermal fibroblasts. AB - The purpose of this study was to evaluate the possibility that the biological changes observed in connective tissue matrix components of photoaging skin may be induced by an alteration of biosynthesis in fibroblasts damaged by reactive oxygen species (ROS). We investigated the effect of ROS induced by xanthine and the xanthine oxidase system on the biosynthesis of connective tissue matrix components, collagen and glucosaminoglycans (GAGs) in cultured human dermal fibroblasts. ROS decreased collagen production and increased GAGs synthesis. Interestingly, these changes were consistent with the biological alterations of connective tissue matrix components observed in photoaging skin. Moreover, catalase and alpha-tocopherol completely prevented the ROS-induced alterations of collagen and GAGs biosynthesis, whereas superoxide dismutase had no effect on the ROS-induced changes. These results suggest that ROS may be one of the factors which cause the biological changes of connective tissue matrix components observed in photoaging skin. PMID- 8215585 TI - Expression of different immunological markers by cultured human melanocytes. AB - The expression of different immunological markers by cultured human melanocytes (MC) in relation to immune phenomena, were investigated on ten different MC cell lines from early (1st) to late (22nd) passage. Four melanocyte lines (MC-a) which had undergone changes in growth behaviour during prolonged culture were included in the study, together with two melanoma lines. Cytospin preparations of the cells were stained for the presence of a set of different immunological markers and a melanoma-associated antigen (MAA). All MC lines, including the MC-a and the melanoma lines, showed expression of MHC class I, IL-1, IL-2, ICAM-1 and the MAA, NKI-Beteb, during all passages tested. Interestingly, four of the MC lines showed staining for the Fc receptor. A tendency towards a stronger expression of ICAM-1 on a higher percentage of cells was observed on MC with increasing passage number, the MC-a and the melanoma lines. Expression of the MAA was strongly reduced for the MC-a lines in comparison with the MC and the M14 melanoma lines. Positive staining for the HLA class II molecules was obtained on MC of intermediate and late passages, and on the MC-a and the melanoma lines in the decreasing order HLA-DR, DP and DQ. Additionally, we carried out a preliminary study showing that cultured MC also produce IL-1 and IL-6. However, we were not able to show the production of biologically active IL-2 testing several cultured MC lines. Nevertheless, the overall results taken together suggest that MC are immunologically important cells that are susceptible to changes during long-term culture. PMID- 8215586 TI - Detection and characterization of endogenous protease associated with desquamation of stratum corneum. AB - In order to identify the endogenous protease associated with stratum corneum (SC) desquamation, we examined properties of proteases in the stratum corneum of normal human skin. SC were obtained by tape stripping, washed in toluene and then dried. The proteolytic activity in SC was measured using peptidyl 4-methyl coumaryl-7-amides (MCAs). The SC was dispersed uniformly in the reaction mixture with dimethylformamide and Triton X-100 and incubated with the peptidyl MCAs. The protease in the SC hydrolysed both Boc-Phe-Ser-Arg-MCA and Boc-Gln-Ala-Arg-MCA (substrates for trypsin) very effectively. The hydrolytic activity was inhibited by the serine protease inhibitors diisopropyl fluorophosphate (DFP), aprotinin, antipain and leupeptin, but not by chymostatin, a chymotrypsin inhibitor. These results show that one or more trypsin-like serine protease is present in the SC of normal human skin. Casein-acrylamide electrophoresis showed that the molecular weight of this serine protease was about 30 kDa. We have previously shown that cells dissociate from human SC sheets in a detergent mixture (N,N dimethyldodecylamine oxide and sodium lauryl sulphate). This cell dissociation was inhibited by aprotinin and leupeptin. In addition, the proteolytic activity in the outer SC was higher than that in the inner SC, and the activity in the SC of scaly skin induced by SLS treatment was higher than that of untreated skin. These results strongly suggest that the trypsin-like serine protease described here is involved in SC desquamation. PMID- 8215587 TI - Genotoxicity of blue rayon extracts from river waters using sister chromatid exchange in cultured mammalian cells. AB - Using cultured Chinese hamster lung (CHL) cells, sister chromatid exchange (SCE) assays were carried out with blue rayon extracts recovered at seven sampling locations from the Katsura, Nishitakase and Kamo Rivers, tributaries of the Yodo River, in Kyoto City, Japan. The downstream extracts of wastewater treatment plants showed higher SCE frequencies than the upstream extracts both with and without metabolic activation, suggesting that the effluents from wastewater treatment plants were the possible pollution sources of genotoxic chemicals in the rivers. The results show the possible use of SCE in CHL cells for the monitoring of genotoxicity of blue rayon extracts from river waters. In addition, simultaneous treatment with sodium thiosulfate significantly reduced the frequencies of SCE induced by blue rayon extracts. PMID- 8215588 TI - Heavy metal and selenium levels in feathers of young egrets and herons from Hong Kong and Szechuan, China. AB - Several species of herons and egrets frequently nest in colonies in areas where humans also concentrate. Since the birds feed on intermediate-sized fish that themselves concentrate pollutants, they can be used not only to assess the levels of contaminants in avian tissues but as indicators of contaminants in the environment. The concentration of heavy metals and selenium in the breast feathers of fledgling black-crowned night herons Nycticorax nycticorax and Chinese pond herons Ardeola bacchus from the Tu Jing Yan heronry outside Chengdu, Szechuan Province in China; and from fledgling black-crowned night heron, little egret Egretta garzetta, great egret Egretta alba and cattle egret Bubulcus ibis from the Mai Po heronry in Hong Kong, were determined. Breast feathers were also collected from adult great egrets in Hong Kong. Adult great egrets had significantly higher levels of all heavy metals than did young great egrets. There were no significant interspecific differences in metal levels among the young at Szechuan China, except for chromium (pond herons had higher levels). There were significant differences among the young nesting at Hong Kong for all metals examined. Great egrets had lower, and night herons had higher, levels of lead than the other young. Night herons also had the highest levels of cadmium, manganese, and selenium compared to the other young. Great egret chicks had the lowest mercury levels, while little egret had the highest levels. Lead levels for all the birds in both Hong Kong and Szechuan were among the highest in the world, and this was attributed to the continued use of leaded gasoline. PMID- 8215589 TI - Distribution patterns of polychlorinated biphenyl congeners in harbor seal (Phoca vitulina) tissues: statistical analysis. AB - Tissue samples from five harbor seals (Phoca vitulina) have been analyzed for coplanar and other polychlorinated biphenyl (CB) congeners, in order to measure variations in levels and patterns of the CBs. Blubber samples contained the highest levels of CBs in all animals; kidney and liver were relatively high-level tissues. CB-153 and CB-138 were the most abundant CB congeners in all samples analyzed. Variations in the patterns of CB congeners in tissues were studied by principal component analyses and multivariate analysis of variance. The CB congener patterns in seals from different geographical regions had distinctly different patterns, whereas the patterns appeared quite similar in tissues within each seal. Based on multivariate analysis of variance, it was, however, possible to detect some systematic variation of the principal components with individual seals and with tissue type within the seals. The assessment of differences in CB congener patterns was possible by comparison to results obtained by repeated analyses of a quality control sample. The calculated dioxin toxic equivalents of the CB congeners followed the levels of the CB congeners, with the highest levels being found in the blubber samples. PMID- 8215590 TI - Distribution of hydrophobic ionizable xenobiotics between water and lipid membranes: pentachlorophenol and pentachlorophenate. A comparison with octanol water partition. AB - We have studied distribution of pentachlorophenol (PCP)--a major environmental pollutant--between egg-phosphatidylcholine (egg-PC) membranes and water. The objectives were (1) to compare the membrane-water partition of the un-ionized (HA) and ionized (A) PCP, and (2) to establish similarities and differences between the partition of PCP into lipid membranes and into octanol. The studies were made with egg-PC liposomes. It is shown that the distribution isotherms can be understood in terms of the Langmuir-Stern-Grahame adsorption model. The model is applicable to both the HA and A species; it takes into account the electrostatic interactions at the membrane-water interface charged by the adsorbed pentachlorophenate. Relationships between the membrane surface adsorption and bulk partition characteristics were presented and used to relate the partition of PCP into egg-PC membranes to those for octanol-water systems. Results (egg-PC membranes): bulk distribution coeff. gamma HA = 2.9 x 10(5), gamma A = 1.6 x 10(4), association constant KmHA = 2.9 x 10(5) M-1, KmA = 0.7 x 10(5) M-1, adsorption site area PsHA = 0.6 nm2, PsA = 3.5 nm2, and linear partition coeff. Beta mHA = 550 microns, beta mA = 30 microns. Comparable to gamma HA and gamma A for octanol-water are P(ow)(HA) approximately 1.3 x 10(5) and P(ow)(A) approximately 30. The major difference is in the distribution of ionized PCP which is several hundred times greater for egg-PC membranes compared to octanol. The difference is associated with the properties of the membrane water interface. PMID- 8215591 TI - Cancer risk and tetrachloroethylene-contaminated drinking water in Massachusetts. AB - A population-based case-control study was used to evaluate the relationship between cases of bladder cancer (n = 61), kidney cancer (n = 35), and leukemia (n = 34) and exposure to tetrachloroethylene from public drinking water. Subjects were exposed to tetrachloroethylene when it leached from the plastic lining of drinking water distribution pipes. Relative delivered dose of tetrachloroethylene was estimated, using an algorithm that accounted for (1) residential history and duration, (2) whether lined pipe served the neighborhood, (3) distribution system flow characteristics, and (4) pipe age and dimensions. Whether or not latency was considered, an elevated relative risk of leukemia was observed among ever exposed subjects (adjusted OR = 1.96, 95% CI = 0.71-5.37, with latency; adjusted OR = 2.13, 95% CI = 0.88-5.19, without latency) that increased further among subjects whose exposure level was over the 90th percentile (adjusted OR = 5.84, 95% CI = 1.37-24.91, with latency; adjusted OR = 8.33, 95% CI = 1.53-45.29, without latency). When latency was ignored, there was also an increased relative risk of bladder cancer among subjects whose exposure level was over the 90th percentile (adjusted OR = 4.03, 95% CI = 0.65-25.10). Given that tetrachloroethylene is a common environmental and workplace contaminant in the United States, its carcinogenic potential is a matter of public health concern. PMID- 8215592 TI - Exposure to tetrachloroethylene via contaminated drinking water pipes in Massachusetts: a predictive model. AB - A computer model was developed to estimate exposure to tetrachloroethylene leaching from drinking-water pipes in Massachusetts between 1968 and 1979. The model was to be used for an epidemiologic study of cancer in five communities in Massachusetts. This model assigned a relative cumulative exposure score to each individual participant in the study, based on the geometry, size, age, and water flow through the water pipe that supplied a particular household and on the individual's duration of residence in that household. The results of modeling showed a wide range of exposure levels among the study participants. The epidemiologic study is described in the accompanying paper by Aschengrau et al. PMID- 8215593 TI - Sick building syndrome in a Canadian office complex. AB - A comprehensive questionnaire survey with limited environmental measurements was undertaken in a large sealed office complex where health complaints had been made by employees since the complex was first occupied. Most respondents suffered from upper respiratory tract irritation, eye and skin irritation, and many less specific complaints. Symptoms started shortly after first employment, were troublesome only at work, and persisted at other work locations within the complex. Employees who worked in cubicles tended to complain more than those who worked in open areas or closed offices; however, evidence of less than optimal ventilation, temperature, and humidity correlated poorly with symptom prevalence. The building was designed and ventilated for open-plan use; later partition into offices and cubicles appeared to aggravate the situation. Although concern about pregnancy outcome was expressed by women who conceived while employed at the complex, rates of spontaneous abortion and fetal defect were close to expectation. PMID- 8215594 TI - Performance, mood, and health during exposure to intermittent odors. AB - The effects of intermittent bursts of pleasant, unpleasant, and no experimental odor on human task performance, mood, and perceived health were tested in this study. Odors did not influence any of these measures; however, subjects who had been exposed to the malodors reported retrospectively that they thought the odors had a negative effect on all of these factors. These findings have implications for the methodological design and interpretation of air quality studies. PMID- 8215595 TI - Efficacy of volatile organic compounds in evoking nasal pungency and odor. AB - Sensory irritation (pungency) figures prominently among the symptoms associated with polluted indoor environments. In order to separate the pungent from the olfactory response, we measured nasal pungency thresholds in subjects lacking olfaction (anosmics) and odor thresholds in normal controls (normosmics) for a homologous series of ketones and for selected secondary and tertiary alcohols and acetates. As seen previously for homologous alcohols and acetates, both types of nasal thresholds decreased with increasing carbon chain length. Pungency thresholds decreased exponentially with chain length. With respect to all nonreactive chemicals studied so far, threshold nasal pungency is achieved at a fairly constant percentage of vapor saturation, irrespective of molecular size or chemical functional group. Such a relationship does not hold for odor thresholds. The outcome for pungency implies an important role for a physical, rather than chemical, interaction with nasal mucosa. PMID- 8215596 TI - Possible time-dependent sensitization to xenobiotics: self-reported illness from chemical odors, foods, and opiate drugs in an older adult population. AB - The present paper summarizes key features of time-dependent sensitization (TDS) in neuropharmacology (progressive amplification of behavioral, neuronal, endocrine, and/or immune responses to repeated intermittent exposures to an environmental agent or cross-sensitizing agents) as a possible model for cacosmia (subjective sense of feeling ill from low levels of environmental chemical odors) in nonindustrial and industrial populations; and extends previous cacosmia research in nonpatient populations to an elderly sample. This study examined the symptom and psychological profiles of 263 older adults (aged 60-90 y, 71% women, 29% men); 57% reported that at least one chemical and 17% reported that at least four of five chemicals (pesticide, automobile exhaust, paint, new carpet, perfume) made them feel ill. Cacosmia ratings correlated weakly and negatively with age (r = -0.19, p = .001) over the whole sample. Cacosmia correlated significantly with self-reported illness from foods that may mobilize or generate opioid peptides (wheat, dairy, eggs) (r = 0.32, p < .0001) and with illness from opiate drugs (r = 0.23, p < .0001). When the sample was divided into four cells on the basis of above-versus below-median total chemical-induced illness score (CI) and total food-induced illness score (FI), the high CI and high FI, high CI only, and high FI only groups had more frequent indigestion, and the high CI group had more frequent difficulty concentrating than the groups below median for illness from both chemicals and foods (NOILL), even after covarying for age and anxiety. The most cacosmic subjects noted higher prevalence of physician diagnosed allergies and irritable bowel than did noncacosmic subjects. In contrast with previous young adult cohort studies, the older illness groups did not differ with regard to sex distribution, depression, shyness, or repressive defensiveness. When considered with prior surveys of young adults, the present findings are consistent with the presence of previously established, time dependent sensitization to multiple xenobiotic agents in susceptible individuals for whom psychological variables do not explain the symptom of cacosmia. If cacosmia is a symptom of TDS, then the neuropharmacology literature suggests the possibility of excitatory amino acid, hypothalamic-pituitary-adrenal axis, dopaminergic, and/or opioid involvement. Prospective studies with objective measures testing the possible induction of TDS to specific chemicals are indicated. PMID- 8215597 TI - Acute effects of a winter air pollution episode on pulmonary function and respiratory symptoms of children. AB - The acute respiratory effects of a wintertime air pollution episode were studied in a general population sample of 112 children who were 7-12 y of age and who lived in a nonurban community. Spirometry was performed on 6 d, with a fixed interval of 3 wk between successive tests. During an air pollution episode, an additional pulmonary function test was made. Acute respiratory symptoms of the children were noted in a diary. Ambient concentrations of sulfur dioxide, black smoke, particulate matter with an aerodynamic diameter less than 10 microns, and nitrogen dioxide were considered as exposure variables. The association of air pollution with pulmonary function and prevalence of acute respiratory symptoms was assessed by individual linear regression analysis and time series analysis, respectively. In February 1991, an air pollution episode occurred during which daily average sulfur dioxide concentrations were slightly above 100 micrograms/m3, and particulate matter (with an aerodynamic diameter of less than 10 microns) concentrations reached 174 micrograms/m3. During the episode, forced vital capacity, forced expiratory volume in 1 s, and maximal mid-expiratory flow were lower than on baseline tests. Significant negative associations were found between the concentration of sulfur dioxide, black smoke, and particulate matter with an aerodynamic diameter of less than 10 microns. No association between prevalence of acute respiratory symptoms and the concentration of these compounds was found. PMID- 8215598 TI - The association of air pollution and mortality: examining the case for inference. AB - An association between air pollution measured as particulate matter, and mortality has been reported in several different locations. These studies have been conducted over a wide range of climates and populations. The time-series studies, which examine the joint occurrence of daily fluctuations in air pollution and mortality, provide the strongest evidence of a true association. However, several criteria, including the consistency of the results, need to be explored before causality is inferred from these studies. A striking consistency in the results was observed, after the different studies were converted into a common metric. The mean effect of an 10 micrograms/m3 change in PM10 implied by these studies varies between 0.64 and 1.49%. The fulfillment of other criteria, including specificity, presence of a dose-response relationship, and coherence of results, lend strong support to the existence of an actual association between particulate matter and mortality. However, the biologic mechanism is not well understood at this time. In addition, the precise measure of the pollutant responsible for the health effect--total suspended particles, PM10, fine particles, sulfates, acidic aerosols, sulfur dioxide, or some as yet unmeasured pollutant--is unclear, based on current available evidence. PMID- 8215599 TI - What is the relationship between hemolytic potential and fibrogenicity of mineral dusts? AB - The hemolytic reaction to a dust is often used as a potential indicator of fibrogenicity of silicon dioxide polymorphs. However, occasionally the hemolytic response may not correlate with the observed fibrotic response in vivo. For example, amorphous silicas are very hemolytic but have little or no fibrogenic activity. In our study, heat treatment was used to alter alpha-cristobalite, a known fibrogenic dust, to a more hydrophobic surface. Comparisons were made between heated and unheated alpha-cristobalite for hemolytic activity in vitro and for lung response in vivo. Heat treatment resulted in decreased hemolytic response, but no change in the fibrotic response occurred in vivo. In addition, the heat treatment resulted in increased initial dust accumulation, reduced short term clearance, and enhanced long-term clearance in vivo. Increased inflammatory cell recruitment was also observed in lungs of animals exposed to alpha cristobalite. Thus, whereas heat-induced surface changes in alpha-cristobalite markedly altered the hemolytic activity of the particles, no changes were observed in the fibrotic response. PMID- 8215600 TI - Cholinesterase and self-reported pesticide exposure among pregnant women. AB - Ascertainment of exposure to cholinesterase-inhibiting pesticides in pregnant subjects is complicated by altered enzyme activity that results from metabolic changes associated with pregnancy. Nevertheless, this study found a high correlation (Pearson chi-square = 13.67, p = .008) between classification of pesticide exposure using self-reported interview information and plasma cholinesterase activity for 203 pregnant women for whom three trimester cholinesterase values were available. All plasma cholinesterase activity values were referenced, by trimester, to a larger sample of 1,050 plasma cholinesterase values from 535 pregnant women. Subjects who lived nearest to agricultural land and who reported that they worked with pesticides in agricultural and other occupations tended to have lower plasma cholinesterase activity than those who reported use of household pesticides only. PMID- 8215601 TI - The role of agricultural pesticide use in the development of non-Hodgkin's lymphoma in women. AB - Non-Hodgkin's lymphoma has been found to be associated with agricultural pesticide use in men, but little is known about the risk in women. In a recent population-based, case-control study conducted in eastern Nebraska, no increased risk of non-Hodgkin's lymphoma was found in women who had ever lived or worked on a farm (odds ratio [OR] = 1.0). Neither the use of insecticides (OR = 0.8) nor herbicides (OR = 0.7) on the farm was associated with non-Hodgkin's lymphoma; however, the number of women who mixed or applied pesticides was small, particularly in comparison to men on farms. Small nonsignificant associations were observed among the women who personally handled insecticides (OR = 1.3) or herbicides (OR = 1.2). Women who personally handled organophosphate insecticides had a significant 4.5-fold increased risk of non-Hodgkin's lymphoma. Use of chlorinated hydrocarbon insecticides was associated with an OR of 1.6; however, the use on dairy cattle was associated with a 3-fold increased risk. Pesticide related risks were greater among women with a family history of cancer, particularly a history of lymphatic or hematopoietic cancer among first-degree relatives. PMID- 8215602 TI - Effect of exposure to organophosphate pesticides on serum cholinesterase levels. AB - In this paper are reported the effects of organophosphate pesticide exposure. Agricultural workers were compared with an age- and sex-matched control group selected from the general population. A significant difference was detected (Student's t = 1.99, p = .05) between the median activity levels of serum cholinesterase in agricultural workers at the end of the work day (mean 4.44, 95% CI = 4.12-4.77), compared with those in the control group (mean = 4.85, 95% CI = 4.57-5.13). The decrease in cholinesterase activity, measured at the beginning (mean = 4.70, 95% CI = 4.38-5.02) and end of the work day, was very significant (paired t = 2.70, p = .01). An interaction was identified between the type of work and the worker's age. Younger workers tended to perform more dangerous activities, and they experienced a greater decrease in cholinesterase activity. This study indicates that subclinical intoxication of agricultural workers, by pesticides, is occurring in Mexico and indicates the need for primary prevention programs that address occupational contact with such substances. PMID- 8215603 TI - Pesticides in the workplace: a worldwide issue. PMID- 8215604 TI - Multiple chemical sensitivity: respect the observations ... suspect the interpretations? PMID- 8215605 TI - Symptoms, syndrome, and semantics: multiple chemical sensitivity and chronic fatigue syndrome. PMID- 8215606 TI - Epidemiological study of endocrinological effects of carbon disulfide. AB - One hundred seventeen viscose rayon workers exposed to carbon disulfide, and 66 workers who were not exposed to any toxic agent in the working environment, underwent an endocrinological examination that included determination of thyroxine, luteinizing hormone, follicle-stimulating hormone, prolactin, and testosterone in serum by radioimmunoassay methods. In the viscose rayon factory, the working conditions had not changed subsequent to 1932. Personal monitoring performed in 17 jobs showed that carbon disulfide exposures varied from 4 to 112 mg/m3. A carbon disulfide cumulative exposure index was calculated for each individual. Univariate analysis of the hormone levels versus exposure showed significantly lower levels of prolactin in the exposed versus nonexposed subjects (p = .01). After adjustment for age, alcohol, smoking, body mass index, and stress level, the carbon disulfide cumulative exposure index was not associated with any of the hormones. This discrepancy from previous studies may result from differences in exposure, in selection of the population, or in confounding biases. PMID- 8215607 TI - Clinical evaluation of the fetus and neonate. Relation between intra-partum cardiotocography, Apgar score, cord blood acid-base status and neonatal morbidity. AB - The relation between intra-partum cardiotocography (CTG), cord blood acid-base status, Apgar score and neonatal morbidity was studied in 1228 consecutively live born babies and in a subgroup of 200 babies (148 babies with a 1 min Apgar score < or = 8 and 52 randomly selected babies with a 1 min Apgar score > or = 9). The scores for the individual components of the 1 min Apgar score were strongly associated with each other, whereas the scores for the individual components of the 5 min Apgar score were less strongly associated. At 1 min the scores for muscle tone, reflex irritability and respiration but not the scores for heart rate and skin colour were associated with arterial and venous cord blood pH (low scores being associated with low pH). Out of the individual components of the Apgar score, heart rate and reflex irritability at 1 min were the best discriminators between "healthy or relatively healthy" and "severely ill" babies. Intrapartum CTG, total Apgar score and cord blood acid-base status were only weakly related. Venous cord blood pH was the best predictor of the 1 min Apgar score. Intra-partum CTG (silent pattern), 5 min Apgar score and venous cord blood pH were the best predictors of severe neonatal morbidity. PMID- 8215608 TI - Serotonin induces progesterone release from human granulosa cells in a superfused granulosa cell system. AB - The dynamics of the release of progesterone (P) by human granulosa cells (GCs) was investigated in a granulosa cell-superfusion system using serotonin (5-HT), propranolol (PR), or mianserin (MI). Granulosa cells were obtained from 8 women undergoing in-vitro fertilization and embryo transfer. Progesterone was measured using radioimmunoassay. Serotonin (100 pMol) induced P release from human GCs. This effect was specifically blocked by 100 pMol MI whilst 100 pMol PR was ineffective in this condition. The results suggest, that the superfused GC system is suitable for studying the dynamics of steroid secretion by human GCs. PMID- 8215609 TI - The bone mineral density change with aging of Japanese women measured by single energy X-ray absorptiometry and dual energy X-ray absorptiometry. AB - The calcaneus bone mineral density of 473 Japanese women was measured by single energy X-ray absorptiometry (SXA) and the vertebrae bone mineral density of 198 Japanese women was measured by dual energy X-ray absorptiometry (DEXA). The calcaneus bone mineral density of Japanese women starts decreasing from age 30, and the rate of decrease accelerates from the age of 50. The vertebrae bone mineral density starts decreasing from the age of 35, and a conspicuous decrease can be seen from the age of 50 as well. Because bone deterioration of Japanese women is thought to start earlier than Caucasian, 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- 8215610 TI - When applied to facial skin, does estrogen ointment have systemic effects? AB - We examined cytological vaginal smears of 17 women before and after three months of dermal estrogen (1 g of 0.01% estradiol ointment or 0.3% estriol ointment once daily), applied to the face for dermatological indications. The mean age was 57.1 +/- 7.6 years (range from 46 to 66). Seven women had estrogenic smears (more than 10% superficial cells) before therapy. Nine women were treated with 0.01% estradiol ointment and 8 were treated with 0.3% estriol ointment. Both groups had gynecological examinations including cervical and vaginal smears before and after treatment and also monthly measurements of serum follicle-stimulating hormone, prolactin and estradiol levels. Serum hormone levels and the appearance of vaginal smears showed no significant change during treatment. PMID- 8215611 TI - Detection and typing of human papillomavirus infection affecting the cervix, vagina and vulva. Comparison of DNA hybridization with cytological, colposcopic and histological examinations. AB - The sensitivity of human papillomavirus (HPV) detection was compared by colposcopy, histology and DNA hybridization among 304 women with abnormal Papanicolaou (Pap) smear. Colposcopically directed biopsies revealed HPV infection in 71% of cases, DNA hybridization in 35%, and both together in 78%. DNA hybridization detected HPV in 24% of the 84 benign cases with no histological signs of HPV, in 32% of the 133 condylomas verified by biopsies and in 51% of the 85 cases with intraepithelial neoplasia, 95% of which presented histological signs of HPV. The pattern of occurrence of different HPV-types resembled findings in earlier reports. HPV infection is common with abnormal Pap smears and it can be identified relatively reliably by means of cytology, colposcopy and histology. DNA hybridization serves as a complementary technique which may reveal the oncological potential of the virus. PMID- 8215612 TI - Pseudo-decidualization at the site of implantation in tubal pregnancy. AB - The tissue from three tubal pregnancies at the site of implantation has been investigated with light and electron microscopy. Large seemingly "decidual" cells were found to be present between the anchoring villi and the tissue of the uterine tubes. These cells are or cytotrophoblastic column origin. Through discontinuities of the syncytiotrophoblast they migrate into the underlying tissue were they grow and synthesize large amounts of glycogen. It is suggested that these cells be named pseudo-decidual cells in order to distinguish them clearly from genuine decidual cells to which they only bear a resemblance on the light microscopical level. The fibrinoid present at the utero-placental interface in ectopic implantation cannot be found in ectopic implantation. From this fact it is deduced that fibrinoid is formed through the action of genuine decidual cells and therefore must be of maternal origin. PMID- 8215613 TI - The modulatory effect of catecholamines on gonadotropin-stimulated granulosa cell steroid secretion. AB - The physiological role of catecholamines in the regulation of gonadotropin stimulated ovarian steroid secretion is unclear. This study was undertaken to investigate the influence of catecholamines on gonadotropin stimulated cultured human granulosa cells under serum-free conditions. Adrenaline and dopamine had no influence on LH stimulated estradiol production. Noradrenaline, however inhibited it (P < 0.01). FSH response was enhanced by adrenaline and decreased by dopamine and noradrenaline (P < 0.05). Noradrenaline and adrenaline decreased the progesterone stimulating effect of LH (P < 0.01), but dopamine had no influence. Adrenaline treatment enhanced, dopamine and noradrenaline decreased slightly the progesterone production of FSH treated granulosa cells (P < 0.05). The results suggest that catecholamines modulate the stimulating effect of gonadotropins. PMID- 8215614 TI - Coping with rheumatoid arthritis. PMID- 8215615 TI - Prediction of the progression of joint space narrowing in osteoarthritis of the knee by bone scintigraphy. AB - OBJECTIVES: To test the hypothesis that bone scintigraphy will predict the outcome of osteoarthritis (OA) of the knee joint. METHODS: Ninety four patients (65 women, 29 men; mean age 64.2 years) with established OA of one or both knee joints were examined in 1986, when radiographs and bone scan images (early and late phase) were also obtained. The patients were recalled, re-examined, and had further radiographs taken in 1991. Paired entry and outcome radiographs were read by a single observer, blinded to date order and other data. Scan findings and other entry variables were related to outcome. Progression of OA of the knee was defined as an operation on the knee or a decrease in the tibiofemoral joint space of 2 mm or more. RESULTS: Over the five year study period 10 patients died and nine were lost to follow up. Fifteen had an operation on one or both knees (22 knees). Of the remaining 120 knees (60 patients) analysed radiographically, 14 (12%) had progressed in the manner defined. Of 32 knees with severe scan abnormalities, 28 (88%) showed progression, whereas none of the 55 knees with no scan abnormality at entry progressed. The strong negative predictive power of scintigraphy could not be accounted for by disease severity or any combination of entry variables. Pain severity predicted a subsequent operation, but age, sex, symptom duration, and obesity had no predictive value. CONCLUSIONS: Scintigraphy predicts subsequent loss of joint space in patients with established OA of the knee joint. This is the first description of a powerful predictor of change in this disease. The finding suggests that the activity of the subchondral bone may determine loss of cartilage. PMID- 8215616 TI - Labial capillary microscopy in systemic sclerosis. AB - OBJECTIVES: To investigate whether in vivo capillary microscopy of the lower lip mucosa can be used to assess microvascular disease in systemic sclerosis. METHODS: Thirteen patients with systemic sclerosis and 11 healthy control subjects were studied by conventional nailfold capillary microscopy and labial capillaroscopy. The following parameters were analysed: loop length; loop width (maximum distance between the arteriolar and venular limbs); loop density (number of capillaries/mm2); venular plexus visibility; megacapillaries; and the architectural arrangement of the capillary network. RESULTS: A typical 'scleroderma pattern' at the nailfold was observed in 12 of 13 (92%) patients with systemic sclerosis. Labial capillaroscopy showed a different morphological pattern of microangiopathy. A diffuse architectural derangement of the capillary network was the most striking abnormality in 12 (92%) patients. Labial capillaries in the patients with systemic sclerosis were shorter (mean (SD) loop length 133 (32.2) microns) than in healthy controls (211 (48.4) microns) and showed an increased loop width (41.7 (13.1) v 27.6 (5.5) microns in controls. The loop density was 10.5 (4.6) capillaries/mm2 in patients with systemic sclerosis and 9 (1.7) capillaries/mm2 in controls. Labial capillaroscopy in patients with systemic sclerosis did not provide definite evidence of enlarged capillaries or avascular areas, or both, even where such abnormalities were clearly evident at the nailfold. CONCLUSIONS: This study shows that labial capillary microscopy is a simple, non-invasive technique which allows a careful morphological assessment of the mucosal microcirculation. Labial capillaroscopy in patients with systemic sclerosis showed significant microvascular changes with respect to the controls. The results of labial and nailfold capillaroscopy are not superimposable, even if some common findings, such as architectural derangement, are present. PMID- 8215617 TI - Osteoarticular infection in intravenous drug abusers: influence of HIV infection and differences with non drug abusers. AB - OBJECTIVES: To determine (a) the influence of HIV in developing osteoarticular infections in intravenous drug abusers (IVDAs) and (b) the differences between the clinical features of osteoarticular infections in IVDAs and a control group of non-IVDAs. METHODS: A comparative study of the clinical features of osteoarticular infections in all HIV positive and HIV negative IVDAs admitted to the departments of rheumatology and internal medicine during a 10 year period was carried out. The joint infections of all IVDAs, irrespective of HIV status, were compared with those of a control group of non-IVDAs lacking risk factors for HIV infection. RESULTS: A total of 482 HIV positive and 85 HIV negative IVDAs was studied, in whom 25 (5%) and six (7%) osteoarticular infections were found respectively. There were no differences in age, sex, joints affected, and causative agents between these two groups. A comparison of the 31 (5.5%) osteoarticular infections in all IVDAs with 21 infections in 616 (3.4%) non-IVDAs showed significant differences in the mean age (27.5 v 54), the frequency of affection of the axial joints (hip, sacroiliac, and sternocostal joints) (64.5% v 16.6%), and in the incidence of Candida albicans (19% v 0%). CONCLUSIONS: (1) HIV may not predispose to osteoarticular infections in IVDAs. (2) The hip, sacroiliac, and sternocostal joints (axial joints) were most commonly affected in IVDAs. (3) In Spain, unlike other countries, Gram positive bacteria and C albicans seem to be predominant agents in osteoarticular infections in IVDAs, with a low incidence of Gram negative bacteria. PMID- 8215618 TI - Polymyositis and dermatomyositis: no persistence of enterovirus or encephalomyocarditis virus RNA in muscle. AB - OBJECTIVES: A persistent infection of enteroviruses and cardioviruses has been implicated in polymyositis and dermatomyositis, but conventional hybridisation studies of the presence of enterovirus RNA and encephalomyocarditis (EMC) virus RNA in affected muscle have yielded conflicting results. To investigate further the possibility of viral persistence, the presence of viral RNA in muscle from patients with adult onset polymyositis and dermatomyositis was investigated using a polymerase chain reaction (PCR) technique. METHODS: Muscle tissue was obtained from 10 patients with polymyositis and five patients with dermatomyositis, all with adult onset active disease. A PCR was performed using primers with high specificity for enterovirus and EMC virus RNA, followed by Southern blot hybridisation with an oligonucleotide probe directed against the internal portion of the amplified product. A PCR directed against the Abelson tyrosine kinase mRNA served as an internal control for the presence and quality of RNA. RESULTS: A specific amplification for enterovirus or for EMC virus could not be seen in any of the muscle biopsy samples, despite a sensitivity of about 30 plaque forming units for enterovirus and of 100 plaque forming units for EMC virus. Southern blot hybridisation confirmed these results in that positive controls hybridised with the oligonucleotide probe, but no signal was obtained with the muscle specimens. CONCLUSION: A sensitive and specific PCR technique showed no evidence of the presence of enterovirus or EMC virus RNA in muscle samples from patients with polymyositis or dermatomyositis. These data do not support the proposal that viral RNA persistence plays a part in these idiopathic inflammatory myopathies. PMID- 8215619 TI - Physical activity as a determinant of bone conservation in the radial diaphysis in rheumatoid arthritis. AB - OBJECTIVES: To determine if increasing physical activity is protective of diaphysial (cortical) bone mass METHODS: Fifteen patients attending two rheumatology clinics who had developed seropositive or classical rheumatoid arthritis up to 26 months previously were studied prospectively for two to three years. Rates of loss (or gain) in bone mass in the radial diaphysis and the trabecular bone of the distal radius were measured by quantitative computed tomography, and in the spine by dual photon absorptiometry. Physical activity was assessed by the Framingham physical activity index. Disease activity was followed at three-monthly clinic visits at which the haemoglobin, erythrocyte sedimentation rate, and platelet count were measured. The urinary hydroxyproline to creatinine ratio and plasma osteocalcin were measured at the beginning and end of the observation period. RESULTS: Eleven patients required treatment with disease modifying drugs but none was given corticosteroids. Those whose physical activity did not improve lost radial diaphysial bone at about 4% annually. There was, however, a statistically significant inverse relation, accounting for 48.5% of the variance, between bone loss at this site and improvement in physical activity as assessed by the Framingham index. The other two sites showed much weaker associations. Adjusting for indices of disease activity hardly affected the first relation. Three biochemical indices related to bone turnover showed weak tendencies to decrease with increasing physical activity. CONCLUSIONS: Peripheral cortical bone, distant from inflamed joints, is conserved more successfully in patients who achieve higher levels of physical rehabilitation. This may have implications for avoiding long bone fractures later in the disease. PMID- 8215620 TI - Methotrexate osteopathy in rheumatic disease. AB - OBJECTIVE: To determine whether two adults with stress fractures receiving low weekly doses of methotrexate had methotrexate osteopathy. CASE REPORTS: Two adult patients developed features consistent with methotrexate osteopathy while receiving low weekly doses of methotrexate. METHODS: Iliac crest biopsy samples were taken and bone histomorphometry carried out. RESULTS: Symptoms resolved when the methotrexate was discontinued. Bone histology showed changes consistent with osteoblast inhibition by methotrexate. CONCLUSIONS: When given in low doses for prolonged periods, methotrexate may have adverse effects on bone, particularly in post-menopausal women. PMID- 8215621 TI - Anticentromere antibodies in subjects with no apparent connective tissue disease. AB - OBJECTIVES: To study the association of anticentromere antibodies (ACA) in various diseases. METHODS: A total of 4800 consecutive serum samples were tested for ACA by indirect immunofluorescence using HEp-2 cells as substrates and by immunoblotting of Molt-4 cell mitotic chromosomal antigens and recombinant CENP-B protein. RESULTS: Anticentromere antibodies were identified in the serum samples of 24 subjects, including eight without apparent connective tissue diseases, six with primary biliary cirrhosis, two with diffuse scleroderma, one with pulmonary hypertension, one with primary Raynaud's phenomenon, one with CREST syndrome (calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia), and five with other connective tissue diseases. By immunoblotting using Molt-4 cells mitotic chromosomal antigens three centromere antigens were recognised by these serum samples. These were: CENP-A (17 kilodalton recognised by 22 of 24 ACA positive serum samples); CENP-B (80 kilodalton recognised by 22 of 24 ACA positive serum samples); and CENP-C (140 kilodalton recognised by 19 of 24 ACA positive serum samples). There was no specific pattern for serum samples from patients with different groups of diseases on immunoblotting. Recombinant CENP-B proteins were all recognised by these samples. Patients without apparent connective tissue disease often had a lower ACA titre than patients with primary biliary cirrhosis. CONCLUSIONS: These data suggest that a positive result for ACA does not always indicate the presence of a connective tissue disease. PMID- 8215622 TI - Cellular hyperimmunoreactivity to rubella virus synthetic peptides in chronic rubella associated arthritis. AB - OBJECTIVES: Immune recognition of the major structural proteins of rubella virus by peripheral blood mononuclear cells and synovial inflammatory infiltrates of a patient with documented chronic rubella associated arthritis was compared with responses of normal healthy rubella virus immunoreactive subjects to establish if there were unusual response patterns associated with rubella associated arthritis in this subject. METHODS: Synthetic peptides (16-33 amino acids in length) representing selected amino acid sequences of the rubella virus envelope (E1 and E2) and capsid (C) proteins were used in lymphocyte stimulation assays with peripheral blood mononuclear cells or synovial inflammatory infiltrates to determine T lymphocyte recognition of antigenic sites within the synthetic peptides. A rubella virus specific polymerase chain reaction was used to determine the persistence of rubella virus in the patient's cells. RESULTS: The patient's peripheral blood mononuclear cells showed abnormally increased lymphoproliferative responses to three E1 synthetic peptides encompassing residues 219-234, 389-411, and 462-481, and one E2 synthetic peptide containing the sequence 50-72, of which the last three were predicted to contain T cell antigenic sites. Although the patient's peripheral blood mononuclear cells showed positive proliferative responses to C synthetic peptides, these were not unusual. The number of synthetic peptides within the E1, E2, and C panels recognised by the patient's peripheral blood mononuclear cells was greater than was previously observed in normal healthy subjects. The recognition of synthetic peptides by synovial inflammatory infiltrates was similar to peripheral blood mononuclear cells but the responses measured were lower. The polymerase chain reaction was negative for rubella virus detection in peripheral blood mononuclear cells and synovial inflammatory infiltrates. CONCLUSIONS: Abnormally increased T cell recognition of antigenic sites within rubella virus E1 and E2 proteins observed in this patient with rubella associated arthritis suggests chronic antigenaemia due to persistent rubella virus in tissue sites other than peripheral blood mononuclear cells or synovial inflammatory infiltrates. PMID- 8215623 TI - Potentiation and inhibition of migration of human neutrophils by auranofin. AB - OBJECTIVES: As auranofin resembles some neutrophil activating sulphur containing compounds, it was decided to investigate whether it had activating effects on neutrophil migration in addition to the published inhibitory effects. METHODS: The Boyden chamber assay was used to determine the migration velocity of human neutrophils. The difference between chemotaxis and chemokinesis was established with a chequerboard assay. RESULTS: Low concentrations of auranofin stimulated human neutrophil migration; concentrations of auranofin higher than 1 mumol/l were inhibitory. Inhibitors of leukotriene formation, or of protein kinase C, had the same effect on auranofin induced potentiation of migration as on fMLP activated migration. Auranofin, at a concentration of 100 nmol/l, caused a transient increase in the cGMP level of neutrophils. The auranofin induced increase in migration was strongly inhibited by methylene blue and by LY83583, two inhibitors of cGMP accumulation. CONCLUSIONS: The auranofin induced enhancement of migration is partly due to a chemokinetic effect, but mainly due to a chemotactic effect. The potentiating effect of auranofin on migration is not specifically due to the ability of the drug to inhibit protein kinase C activity or to generate leukotrienes. These results suggest that the enhancement of neutrophil migration by low levels of auranofin is related to the enhancement of cGMP levels in neutrophils. PMID- 8215624 TI - Enhancement of crystal induced neutrophil responses by opsonisation of calcium pyrophosphate dihydrate crystals. AB - OBJECTIVES: Little is known about the effect on crystal induced neutrophil responses of the opsonisation of calcium pyrophosphate dihydrate (CPPD) (triclinic) crystals with components of serum and plasma. The purpose of this study was to determine the effects of precoating CPPD crystals with plasma, serum, complement depleted serum, and IgG on a full range of crystal induced neutrophil responses (calcium mobilisation, chemiluminescence, superoxide anion production, non-cytolytic lysosomal enzyme release, and leukotriene synthesis). METHODS: Crystals were precoated with IgG, serum, plasma, or complement depleted serum (heated at 56 degrees C), incubated with neutrophils and the responses monitored with time. Measurement of the extent of neutrophil association with crystals was based on monitoring the decrease in fluorescence intensity of supernatants when crystals and diphenylhexatriene labelled neutrophils were allowed to settle under gravity. RESULTS: Precoating CPPD crystals with IgG, plasma, and serum significantly enhanced chemiluminescence, superoxide anion generation, increases in cytosolic free calcium levels, and non-cytolytic lysosomal enzyme release by neutrophils compared with uncoated CPPD crystals. The enhancement of neutrophil responses by crystals coated with complement depleted serum was less pronounced. The increased neutrophil responses induced by CPPD crystals coated with IgG might have been due to the observed increase in the association of IgG coated crystals with neutrophils. CONCLUSIONS: These data show that there is a marked potentiation of all neutrophil responses to IgG, plasma, and serum coated CPPD crystals. It is suggested that the adsorption of synovial fluid proteins, including IgG and C3b, to CPPD crystals in vivo, results in the opsonised crystals becoming a potent neutrophil stimulant and inflammatory agent. PMID- 8215625 TI - Absence of Epstein-Barr virus carrying cells in synovial membranes and subcutaneous nodules of patients with rheumatoid arthritis. AB - OBJECTIVES: To determine whether the Epstein-Barr virus is present in synovial membranes and subcutaneous nodules of patients with rheumatoid arthritis. METHODS: A sensitive in situ hybridisation technique was applied to tissue sections of 11 synovial membranes and five rheumatoid nodules. RESULTS: Cells carrying the Epstein-Barr virus were not detected using EBER and BHLF1 oligonucleotides in the tissue samples investigated here. CONCLUSIONS: Although it has been suggested that the Epstein-Barr virus could play a part in the aetiology of rheumatoid arthritis, it was not detected in synovial membranes and subcutaneous lesions in this study. PMID- 8215626 TI - Molecular analysis of HLA-DR beta and DQ beta polymorphism in Chinese with rheumatoid arthritis. AB - OBJECTIVES: Several studies have suggested that genetic predisposition to rheumatoid arthritis may be related to the presence of specific polymorphic HLA sequences that are often associated with HLA-DR4 haplotypes. This study was performed to determine if an association exists between Chinese with rheumatoid arthritis and a particular HLA-DR beta or DQ beta subtype. METHODS: This study used the polymerase chain reaction to amplify HLA-DR beta and DQ beta genes, and oligonucleotide probe hybridisation to examine the association of certain polymorphic sequences with rheumatoid arthritis in 23 Chinese patients from Shanghai. RESULTS: An HLA-DR4 associated sequence was significantly increased in the Chinese patients (43%) compared with healthy controls (14%) from the same location (relative risk = 4.6, 95% confidence limits 1.1 to 19.3). Analysis of the third hyperpolymorphic region of DR4 positive samples was performed to detect polymorphic sequences associated with Dw4, Dw10, Dw13, Dw14, Dw15, and KT2 cellular specificities. Examination of this region showed that 91% of patients had sequences encoding amino acids QRRAA (associated with Dw14 and Dw15) or QKRAA (associated with Dw4) compared with 64% of the DR4 positive controls. CONCLUSIONS: Rheumatoid arthritis in the Chinese is associated with HLA-DR4. There is a possible relationship between sequences within the third hyperpolymorphic region of the DRB allele and rheumatoid arthritis in the Chinese. PMID- 8215627 TI - Renal effects of aspirin and low dose methotrexate in rheumatoid arthritis. AB - OBJECTIVES: The aim of this investigation was to study the glomerular and tubular effects of low doses (15 mg) of methotrexate in patients with rheumatoid arthritis with and without combined treatment with aspirin (2 g single dose). METHODS: Renal function was measured by the plasma clearance of EDTA labelled with chromium-51 (51Cr-EDTA) and mercaptoacetyltriglycine labelled with technetium-99m (99mTc-MAG-3). RESULTS: Clearance of 51Cr-EDTA was reduced from 98 (6) to 87 (5) ml/min (mean (SEM)) for patients receiving methotrexate only and further reduced to 76 (5) ml/min for patients receiving methotrexate and aspirin. This effect was reversible as 51Cr-EDTA increased to 85 (6) ml/min during continued treatment with methotrexate alone. Clearance of 99mTc-MAG-3 also decreased from 366 (18) to 315 (17) ml/min in patients receiving methotrexate alone and further to 295 (17) ml/min during treatment with aspirin and methotrexate. Continued treatment with methotrexate alone resulted in a further decrease in the 99mTc-MAG-3 clearance to 253 (17) ml/min. CONCLUSIONS: The study shows that treatment with low doses of methotrexate particularly when combined with aspirin affects glomerular and tubular function. These effects may be of clinical importance and renal function should therefore be monitored with more sensitive methods than serum creatinine as this may not reflect these changes. PMID- 8215628 TI - Treatment of Paget's disease of bone with single dose intravenous pamidronate. AB - OBJECTIVES: To assess the efficacy of a single intravenous infusion of pamidronate in Paget's disease of bone. METHODS: Fourteen patients with active Paget's disease (raised serum alkaline phosphatase, bone pain or neurological involvement) were treated with a single intravenous infusion of 105 mg pamidronate. Patients were assessed for biochemical and clinical improvement for up to two years following treatment. A further infusion was given following symptomatic relapse (pain at a known site of pagetic involvement). RESULTS: Serum alkaline phosphatase fell following treatment, with a nadir 5.9 months after treatment. Bone pain was improved in nine of 12 patients after six months. Retreatment of four patients resulted in a similar response. CONCLUSION: Single dose intravenous pamidronate (105 mg) is a convenient and effective treatment for Paget's disease. PMID- 8215629 TI - Effect of surgical cleaning of the skin on the pathergy phenomenon in Behcet's syndrome. AB - OBJECTIVES: To assess the effect of surgical cleaning of the skin on the pathergy phenomenon in Behcet's syndrome. METHODS: The pathergy phenomenon was assessed in 183 patients with Behcet's syndrome in a single blind study at 48 hours after a needle prick of the forearm skin, cleaned in the conventional way with alcohol, with 10% povidine iodine, with 100% chlorhexidine, and with a 4% aqueous solution of chlorhexidine. RESULTS: The surgical cleaning of the forearm with povidone iodine before the application of the needle prick reduced the prevalence of the pathergy reaction to 27% from 48% in the conventionally (by alcohol swab) cleaned forearm. Cleaning the forearm with 100% chlorhexidine reduced the prevalence of the pathergy to 36% from 59% in the conventionally cleaned forearm. No significant changes were observed with a 4% aqueous solution of chlorhexidine. CONCLUSIONS: Surgical cleaning of the skin with disinfectants of various concentrations reduces the prevalence of a positive pathergy test in Behcet's syndrome. This implies that more than the disruption of the structural integrity of the dermis and epidermis is involved in the production of the pathergy phenomenon in Behcet's syndrome. PMID- 8215630 TI - Antibodies to retroviral proteins in Sjogren's syndrome. PMID- 8215631 TI - Insufficiency fractures of the sacrum. PMID- 8215632 TI - Absence of antiphospholipid antibodies in Behcet's disease. PMID- 8215633 TI - Anabolic therapy with growth hormone accelerates protein gain in surgical patients requiring nutritional rehabilitation. AB - OBJECTIVE: The authors investigated the effects of exogenous growth hormone (GH) on protein accretion and the composition of weight gain in a group of stable, nutritionally compromised postoperative patients receiving standard hypercaloric nutritional therapy. SUMMARY BACKGROUND DATA: A significant loss of body protein impairs normal physiologic functions and is associated with increased postoperative complications and prolonged hospitalization. Previous studies have demonstrated that standard methods of nutritional support enhance the deposition of fat and extracellular water but are ineffective in repleting body protein. METHODS: Fourteen patients requiring long-term nutritional support for severe gastrointestinal dysfunction received standard nutritional therapy (STD) providing approximately 50 kcal/kg/day and 2 g of protein/kg/day during an initial 7-day equilibrium period. The patients then continued on STD (n = 4) or, in addition, received GH 0.14 mg/kg/day (n = 10). On day 7 of the equilibrium period and again after 3 weeks of treatment, the components of body weight were determined; these included body fat, mineral content, lean (nonfat and nonmineral containing tissue) mass, total body water, extracellular water (ECW), and body protein. Daily and cumulative nutrient balance and substrate oxidation studies determined the distribution, efficiency, and utilization of calories for protein, fat, and carbohydrate deposition. RESULTS: The GH-treated patients gained minimal body fat but had significantly more lean mass (4.311 +/- 0.6 kg vs. 1.988 +/- 0.2 kg, p < or = 0.03) and more protein (1.417 +/- 0.3 kg vs. 0.086 +/- 0.1 kg, p < or = 0.03) than did the STD-treated patients. The increase in lean mass was not associated with an inappropriate expansion of ECW. In contrast, patients receiving STD therapy tended to deposit a greater proportion of body weight as ECW and significantly more fat than did GH-treated patients (1.004 +/- 0.3 kg vs. 0.129 +/- 0.2 kg, p < 0.05). GH administration altered substrate oxidation (respiratory quotient = 0.94 +/- 0.02 GH vs. 1.17 +/- 0.05 STD, p < or = 0.0002) and the use of available energy, resulting in a 66% increase in the efficiency of protein deposition (13.37 +/- 0.8 g/1000 kcal vs. 8.04 g +/- 3.06 g/1000 kcal, p < or = 0.04). CONCLUSIONS: GH administration accelerated protein gain in stable adult patients receiving aggressive nutritional therapy without a significant increase in body fat or a disproportionate expansion of ECW. GH therapy accelerated nutritional repletion and, therefore, may shorten the convalescence of the malnourished patient requiring a major surgical procedure. PMID- 8215634 TI - The two-edged sword of large-dose steroids for spinal cord trauma. AB - OBJECTIVE: In 1990, large-dose steroid administration was advocated in spine injured patients to lessen neurologic deficits. The authors undertook both prospective and retrospective studies to evaluate the response of such profound pharmacologic intervention. SUMMARY BACKGROUND DATA: Of all sources of nonfatal injury, spinal cord trauma remains the most devastating in both cost and impact on the quality of the patient's life. One study found that routine large-dose steroid administration after injury lessened the extent of neurologic injury. After uncommonly prompt and broad lay press publicity, this practice was widely accepted. Biased by knowledge of the known immunosuppressive effects of steroids, the authors suspected that pneumonia was both more frequent and severe in steroid treated patients. METHODS: Thirty-two patients with cervical or upper thoracic spinal injuries (C3-6, 20 patients; C6-7, 6 patients; and T1-6, 6 patients) were studied at an urban level I trauma center from January 1987 to February 1993. Complete spinal cord injury was present in 22 of 32 patients; 14 patients received steroids postinjury. There was no difference in mean age, cord level, age-adjusted injury severity score, or the percent of injury severity score caused by the spinal injury. RESULTS: The length of hospital stay was longer in steroid-treated patients (S) than in nonsteroid (NS) patients, that is, 44.4 days versus 27.7 days, respectively (p = 0.065). Seventy-nine per cent of S patients had pneumonia compared with 50% of NS patients (p = 0.614). There was no statistical difference in the episodes of pneumonia per patient between the two groups (p > 0.05). Prospectively, the authors evaluated sequentially several parameters known to be important in human immune responses to bacterial challenges in nine S and five NS patients. In S patients, both the per cent and density of monocyte class II antigen expression and T-helper/suppressor cell ratios were lower than in NS patients. However, S patients did have an initially higher, earlier boost in some host defense parameters that rapidly declined, and their subsequent response was both blunted and delayed. These differences became even clearer when stratified according to cord level and incomplete versus complete cord status. Not surprisingly, infected patients, whether S or NS, had lower levels of monocyte antigen expression, CR3, and helper/suppressor ratios. CONCLUSIONS: These data do not permit a judgment to be made whether neurologic status was improved by S administration. It is known that vital immune responses were adversely affected, that pneumonia was somewhat more prevalent, and that hospitalization was prolonged and costs therefore increased by an average of $51,504 per admission. Further clinical studies will be needed to determine to what extent these observations offset the putative benefits of large-dose steroids in the treatment of spinal trauma. PMID- 8215635 TI - Hyperinsulinemia after pancreatic transplantation. Prediction by a novel computer model and in vivo verification. AB - OBJECTIVE: The authors evaluated systemic venous insulin release as a cause of the hyperinsulinemia (HNS) associated with pancreatic transplantation (PTX) with respect to the mechanism and metabolic consequences. SUMMARY BACKGROUND DATA: Many investigators believe the postoperative anatomy associated with common PTX techniques to be the sole cause of the two- to threefold posttransplantation HINS. However, this concept remains to be conclusively proved and characterized quantitatively. METHODS: The authors used three approaches to achieve their objectives. First, a computer model was generated based on established data concerning blood flow and tissue insulin extraction to determine whether it was mathematically possible for HINS to be caused by systemic insulin release. Second, HINS clamps were applied to normal dogs using the Andres clamp technique to quantify the in vivo differences in peripheral insulin levels and the metabolic consequences of systemic versus portal insulin infusion. Third, prolonged insulin half-life was evaluated as a possible mechanism of HINS from systemic insulin release by determination of biexponential rates of plasma disappearance from an endogenous pulse of insulin in surgically induced dog models of systemic and portal insulin release. RESULTS: First, the computer model calculated a 1.4- to 2.9-fold increase in peripheral venous insulin levels with systemic versus portal insulin release, verifying mathematically the concept of HINS resulting from systemic insulin release. Second, the actual systemic insulin infusion produced a 1.3- to 1.4-fold increase in peripheral venous insulin levels compared with portal infusion (p < 0.05). No significant differences in hepatic glucose output, total glucose disposal, or glucose infusion requirements were seen. Third, although the basal insulin level was twofold higher in the surgically induced animal models with systemic insulin release (p < 0.003), there were no differences in biexponential insulin clearance parameters. CONCLUSIONS: The HINS produced by systemic insulin release did not significantly alter glucose metabolism and was not the result of altered peripheral insulin clearance parameters. In vivo systemic venous insulin infusion studies produce HINS, but not to the degree calculated by mathematic modeling or that occurs after clinical PTX, making it likely that other factors also play a role in the HINS after PTX. PMID- 8215636 TI - Neutrophil and nonneutrophil-mediated injury in intestinal ischemia-reperfusion. AB - OBJECTIVE: The role of polymorphonuclear neutrophils (PMN) was examined in local and remote organ injury after intestinal ischemia-reperfusion. SUMMARY BACKGROUND DATA: PMN have been found to mediate the local injury in low flow intestinal ischemia-reperfusion. However, in complete intestinal ischemia-reperfusion, prevention of PMN adhesion by monoclonal antibodies to CD11b and CD18 reduces remote but not local intestinal injury. The role of PMN was further investigated in this setting. METHODS: In a rat model of 1-hour complete intestinal ischemia and 4-hour reperfusion. PMN were manipulated in the following four ways: (1) inhibition of oxygen-free radicals using manganese superoxide dismutase and catalase (SOD/CAT), (2) antagonism of PMN elastase using secretory leukocyte protease inhibitor (SLPI), (3) neutropenia using PMN antisera, and (4) inhibition of activation and adhesion using interleukin-1 receptor antagonist (IL-1ra) and tumor necrosis factor binding protein (TNFbp). Lung injury was quantified by the pulmonary permeability index, which is the ratio of bronchoalveolar lavage to blood concentration of radiolabeled bovine serum albumin, and PMN sequestration by myeloperoxidase (MPO) activity. Liver injury was estimated by PMN counts using quantitative histologic examination and by serum glutamic pyruvic transaminase (SGPT). Local injury was quantified by MPO activity and histologic grading. RESULTS: Neutropenia reduced the pulmonary permeability 80% from 11.0 +/- 0.5 x 10(-3) with saline treatment to 5.50 +/- 0.12 x 10(-3); IL-1ra, to 5.62 +/- 0.44 x 10(-3); and TNFbp, to 4.32 +/- 0.18 x 10(-3) (all p < 0.05). Pulmonary MPO rose from 0.03 +/- 0.01 U/g to 0.25 +/- 0.03 U/g (p < 0.05). This was reduced by neutropenia, 0.01 +/- 0.003 U/g, but not by inhibition of oxygen-free radicals or PMN elastase. IL-1ra inhibited PMN sequestration, reducing MPO to 0.12 +/- 0.01 (p < 0.05). Liver injury was 60% dependent on PMN. Ischemia-reperfusion increased SGPT from 20.3 +/- 0.7 IU/L in the sham-treated animals to 97.0 +/- 3.1 IU/L in the experimental animals. Neutropenia reduced this to 48.1 +/- 3.9 IU/L; IL-1ra, to 44.7 +/- 3.7 IU/L; SOD/CAT, to 64.0 +/- 3.38 IU/L; and SLPI, to 57.1 +/- 3.4 IU/L (p < 0.05 in all cases). Local injury was severe and unaffected by manipulation of the PMN. CONCLUSIONS: These data suggest that PMN and their products mediate most of the lung, part of the liver, and none of the local gut injury after intestinal ischemia-reperfusion. PMID- 8215637 TI - The development of gene therapy for the treatment of cancer. AB - OBJECTIVE: The authors sought to develop new treatments for patients with cancer based on the genetic modification of immune lymphocytes and tumor cells designed to increase the host immune reaction against growing cancers. METHODS: Retroviral mediated gene transduction was used to introduce genes into tumor-infiltrating lymphocytes (TIL), and these genetically altered TIL were administered to patients with cancer. Genes coding for cytokines were introduced into tumor cells, and these cells were used to immunize patients against their autologous cancers. RESULTS: In initial studies, the gene for neomycin phosphotransferase was introduced into the TIL of ten patients with advanced cancer to study the survival and distribution of TIL in humans. These studies showed that retroviral gene transduction is a safe and practical method for adding genes to human cells and led to clinical trials in which the gene for tumor necrosis factor (TNF) was inserted into TIL in an effort to increase their therapeutic effectiveness. Phase I trials are currently underway using TIL that secrete up to 100 times the normal level of TNF. More recently, animal experiments have revealed that transduction of tumor cells with cytokine genes can enhance tumor immunogenicity and, thus, increase the recognition of the tumor as foreign by the host. Clinical trials based on these observations have begun in which patients are immunized against their own autologous tumors that were transduced with the genes for TNF or interleukin-2. CONCLUSIONS: Attempts at gene therapy for cancer are underway and have opened new possibilities for the development of cancer treatments. PMID- 8215638 TI - Supporting future surgical innovation. Lung transplantation as a case study. AB - OBJECTIVE: Using lung transplantation as a case study, this article addressed the problem of supporting innovative clinical surgery in an era of increasing pressures for cost containment. SUMMARY BACKGROUND DATA: After sporadic attempts at lung transplantation during the 1960s and 1970s, its clinical development began in earnest during the early 1980s. As a result of a wide range of incremental advances, the results have improved significantly. The Health Care Financing Administration, however, has not yet issued a national policy covering lung transplants and has left the coverage decision to the discretion of its regional contractors. METHODS: The authors surveyed the major commercial insurers, the Blue Cross Blue Shield Association, and a sample of Medicare intermediaries to evaluate the coverage of lung transplantation. They also interviewed the National Heart, Lung, and Blood Institute and industrial firms about their support for clinical research. RESULTS: Government and industry funding were limited, and the development and assessment of lung transplants have been financed predominantly by academic institutions through cross-subsidization from patient care and teaching funds. The major private payers and Blue Cross Blue Shield decided to cover this procedure in the early 1990s. Coverage decisions by Medicare intermediaries, however, revealed considerable variability. Moreover, the absence of a specific diagnosis-related group for lung transplants had considerable consequences for institutions in all-payer states, in which payments appeared to be considerably lower than the mean costs of a transplant procedure (about $110,000). CONCLUSIONS: This analysis indicated that there was a growing disparity between the increasing demand for outcomes data about new procedures and the limited resources available for supporting the development and assessment of new operations. It this disparity is not addressed, the rate of surgical innovation may be jeopardized, and timely outcomes data may not be acquired. It was concluded that provisional coverage within a predetermined research protocol may be a promising mechanism to remedy this situation, providing timely assessment of new procedures before widespread application. PMID- 8215639 TI - Early hormonal changes affect the catabolic response to trauma. AB - OBJECTIVE: The authors sought to determine how temporary insulin suppression might alter the catabolic effects of cortisol, glucagon, and epinephrine. SUMMARY BACKGROUND DATA: The metabolic responses to injury include hypermetabolism, accelerated net skeletal muscle protein breakdown, glucose intolerance, and insulin resistance. These alterations are associated with increased stress hormone concentrations. Insulin elaboration is usually suppressed immediately after an injury but is abundant later during convalescence. An infusion of hydrocortisone, glucagon, and epinephrine increases both stress hormone concentrations and insulin levels. It induces many of the metabolic alterations seen in critically ill patients, but it does not affect net muscle breakdown. METHODS: Seven healthy adults received a stress hormone infusion for 3 days in two separate studies. During one study they, also received an infusion of the somatostatin analogue, octreotide (0.005 micrograms/kg/min), to suppress insulin elaboration for the first 24 hours. During the other study (control), insulin was permitted to rise unchecked. RESULTS: Stress hormone concentrations, hypermetabolism (+/- 20% above basal), and leukocytosis were similar during both study periods. When insulin elaboration was temporarily suppressed, whole-body nitrogen loss was increased during the first 48 hours, and the efflux of amino acids from the forearm after 72 hours of infusion was 60% greater than the control level. CONCLUSIONS: Temporary insulin suppression during physiologic increases in stress hormone concentrations amplified whole-body nitrogen loss and led to the development of accelerated net skeletal muscle protein breakdown. Early hormonal changes after an injury may affect the development of later catabolic responses. PMID- 8215640 TI - Combination anti-CD2 and anti-CD3 monoclonal antibodies induce tolerance while altering interleukin-2, interleukin-4, tumor necrosis factor, and transforming growth factor-beta production. AB - OBJECTIVE: These studies were designed to elucidate the mechanism by which signals delivered by anti-CD2 monoclonal antibody (MoAb) interfere with activational signals delivered by anti-CD3 MoAb and induce long-term graft survival and tolerance. SUMMARY BACKGROUND DATA: Anti-CD2 or anti-CD3 MoAb can prolong allograft survival when administered alone. In combination, they synergistically prolong survival while reducing anti-CD3-associated cytokine toxicity. It was postulated that the mechanism of synergism and reduced cytokine toxicity was related to anti-CD2-induced alterations in anti-CD3-induced T-cell activation. METHODS: C57BL/6 (H-2b) mouse hearts were transplanted to CBA (H-2k) mice. The recipients received anti-CD2 and/or anti-CD3 MoAb intravenously only at the time of initial allografting. Serum from treated animals and culture supernatants from lymphocytes stimulated in vitro with anti-CD3 were examined for interleukin (IL)-2, -4, -6, and -10, tumor necrosis factor (TNF), and transforming growth factor-beta (TGF beta). RNA was isolated from lymphocytes from treated animals and examined for receptor and cytokine gene expression by northern hybridization or reverse transcribed and amplified by the polymerase chain reaction (PCR). RESULTS: Anti-CD2 and anti-CD3 MoAbs alone prolonged graft survival (22.0 +/- 0.5 days and 28.0 +/- 0.5 days, respectively; p < 0.02 and p < 0.01 vs. control, by Wilcoxon signed-rank test). Combined anti-CD2/anti-CD3 MoAbs synergistically prolonged survival indefinitely (> 150 days, p < 0.01) while decreasing cytokine toxicity. Second donor-specific allografts also showed long term survival. The peak serum TNF concentration (2100 units/mL) was reduced 78% by anti-CD2 treatment (455 units/mL). Anti-CD2 inhibited anti-CD3-stimulated proliferation and in vitro production of IL-2 and IL-4, with no alteration of IL 6, IL-10, or TNF. Conversely, there was an increase in the immunosuppressive cytokine TGF beta. PCR analysis showed that anti-CD2 reduced anti-CD3-stimulated IL-2 messenger RNA expression, and by northern analysis, anti-CD2 inhibited anti CD3-stimulated increases in messenger RNA for the CD2 and CD3 receptors themselves. CONCLUSIONS: The combination of anti-CD2 and anti-CD3 MoAbs induced a state of tolerance while decreasing anti-CD3-associated cytokine toxicity. The mechanism was related to anti-CD2-generated alterations in T-cell activation and gene expression. PMID- 8215641 TI - Extended myectomy-myotomy. A therapeutic alternative for total intestinal aganglionosis. AB - OBJECTIVE: That total intestinal aganglionosis (extended Hirschsprung's disease) is uniformly incompatible with life as reported in 1985, is challenged by this series of patients treated over the last 7 years with an alternative therapy, extended myectomy-myotomy of the small bowel. SUMMARY BACKGROUND DATA: A total of 16 neonates worldwide presented with intestinal obstruction secondary to total (extending to the stomach) or near total (to 40 cm of jejunum) intestinal aganglionosis confirmed at one or more leveling operations. METHODS: A patient questionnaire was answered by the surgeon of all 16 patients. RESULTS: The sex distribution was eight boys and eight girls. The definitive operation included extending an antimesenteric myectomy-myotomy from the ganglionic-aganglionic transition zone for variable lengths, the operative design being to create sufficient small bowel length to support life (40-cm minimum, total small bowel maximum). The myectomized bowel was terminated as an end-stroma or as an isolated jejuno-ileal segment. Ten of 16 patients have survived (62.5%) whose length of ganglionated bowel varies from 0 to 40 cm (mean, 12.4 cm; median, 6.0 cm). Six patients have died from 1 to 33 months after operation (mean, 9.5 months; median, 5.0 months) of gut-induced infection (n = 5) and respiratory failure (n = 1); their ganglionated bowel length was similar to survivors (range, 0-26 cm; mean, 9.2 cm; median, 8.0 cm). Of the 16 patients, 15 have received enteral nutrients through the myectomized bowel. Of ten survivors, strikingly two are totally gut nourished (2 cm, 7-cm length of ganglionated bowel), six receive from 1/5 to 4/5 of total calories enterally, and one receives minimal enteral feeding. CONCLUSIONS: From these patients we have learned that (1) extended myectomy myotomy relieves the obstruction of extended Hirschsprung's disease; (2) aganglionic bowel after extended myectomy-myotomy acts as a passive conduit for proximally propulsed nutrients; and (3) aganglionic bowel after extended myectomy myotomy undergoes adaptive change and is capable of absorbing life-supporting nutrients. These data demonstrate extended myectomy-myotomy to be a therapeutic option for otherwise fatal extended Hirschsprung's disease, either as a potentially definitive therapy or as a putative bridge to intestinal transplantation. PMID- 8215642 TI - An analysis of the association of trauma centers with per capita hospitalizations and death rates from injury. AB - OBJECTIVE: This study used population-based data bases to assess the association of trauma centers with per capita county hospitalization and trauma death rates in the State of North Carolina. SUMMARY BACKGROUND DATA: The current study extended previous work using two North Carolina data bases to assess the association of the presence of a trauma center with per capita county trauma death rates. METHODS: Data on per capita county trauma hospitalizations and deaths were obtained from the state hospital discharge data base and the North Carolina Medical Examiner's data base. Bivariate and multivariate analysis techniques were used. The dependent variables of interest were prehospital, hospital, and total trauma death rates and hospitalization rates for injury. RESULTS: Bivariate analysis identified a number of factors associated with per capita county hospitalizations and trauma death rates. These included the per cent unemployment, racial distribution, county alcohol tax receipts, and advanced life support certified emergency medical services providers. The per capita trauma death rates were significantly lower in counties with trauma centers compared with those without trauma centers (4.0 +/- 0.5 and 5.0 +/- 1.1 deaths per 10,000 population, p = 0.0001, respectively). The per capita hospitalizations for trauma were also lower in counties with trauma centers. Multivariate modeling showed that the presence of a trauma center and advanced life support providers were the best predictors of decreased per capita county trauma death rates. CONCLUSIONS: The study showed that the presence of a trauma center and advanced life support training were the two medical system factors that were the best predictors of the per capita county prehospital and total trauma death rates. These findings are consistent with the hypothesis that trauma centers are associated with a decrease in trauma death rates. PMID- 8215643 TI - Examination of the mechanisms responsible for tolerance induction after intrathymic inoculation of allogeneic bone marrow. AB - OBJECTIVE: This study examined the immunologic mechanism(s) responsible for the induction of transplantation tolerance in rats pretreated with intrathymic inoculation of donor strain bone marrow. SUMMARY BACKGROUND DATA: Induction of unresponsiveness may involve deletion and/or inactivation of donor-reactive T cell precursors maturing in a thymus harboring donor alloantigen or generation of regulatory/suppressor cells. It was reasoned that, if unresponsiveness is caused by deletion of alloreactive clones, the presence of additional thymic tissue devoid of donor alloantigen permits normal maturation of T-cells and, thus, prevents induction of tolerance. However, if unresponsiveness were primarily mediated by regulatory/suppressor cells, the presence of noninoculated thymic tissue should not affect the induction of tolerance. METHODS: Three strategies were used to define the cellular basis of cardiac and islet allograft survival in WF recipients of intrathymic LEW donor bone marrow as follows: (1) inoculation of bone marrow either into the native thymus and/or into an ectopic thymus, (2) limiting dilution analyses of the frequency of precursor cytotoxic T-lymphocytes (CTLp), and (3) adoptive transfer to syngeneic secondary hosts. RESULTS: Inoculation of bone marrow into only one lobe of the native thymus and/or into an ectopic thymus did not promote consistent survival of subsequent LEW cardiac allografts. Tolerant hosts displayed significant reductions in CTLp frequencies against donor alloantigens. Adoptive transfer of spleen cells from tolerant WF hosts harboring long-standing cardiac allografts led to permanent survival of LEW cardiac allografts in all secondary recipients. However, transfer of spleen cells from WF animals that received intrathymic LEW bone marrow (but no cardiac allograft) did not promote survival of LEW cardiac allografts in naive secondary hosts. CONCLUSIONS: These results indicate that the unresponsive state after intrathymic inoculation of bone marrow cells is primarily mediated by deletion and/or inactivation of donor-specific T-cell precursors maturing in a chimeric thymus. The demonstration by adoptive transfer studies of putative regulatory/suppressor cells suggested an important role for the persistence of donor alloantigen (supplied by a vascularized allograft) in the maintenance of the unresponsive state. PMID- 8215644 TI - A prospective, randomized, blinded, and placebo-controlled trial of intraoperative intra-arterial urokinase infusion during lower extremity revascularization. Regional and systemic effects. AB - OBJECTIVE: This study was designed to evaluate the safety and regional and systemic effects of three doses of urokinase (UK) infused into the distal arterial circulation during routine operative lower extremity revascularization. METHODS: One hundred thirty-four patients were prospectively randomized to receive one of three bolus doses of UK (125,000, 250,000, or 500,000 U) or placebo (saline) infused into the distal circulation before lower extremity bypass for chronic limb ischemia. Regional (femoral vein) and systemic (arm) blood was sampled before drug infusion, prereperfusion, and postreperfusion, and systemic blood samples were obtained 2 hours postreperfusion. Assays evaluated plasma levels of fibrinogen, fibrin(ogen) degradation products (FDP), fibrin breakdown products (D-dimer and fragment B-beta 15-42), and plasminogen. Patients were monitored for clinically evident bleeding complications. The Wilcoxon rank sum test was used to compare different drug doses with the placebo. RESULTS: Intraoperative bolus UK infusions produced no significant fibrinogen breakdown compared with placebo. There was a dose-related decline in plasminogen levels, which became significant at a dose of 500,000 U of UK (p < 0.001). There were dose-related increases in plasma FDP, which became significant at dose of 250,000 and 500,000 U (p < or = 0.005), and in plasma D-dimer, which were significant at all UK doses (p < 0.001). The changes in plasma fibrinogen and markers of fibrin breakdown were similar in the regional and systemic circulations. There was no increase in operative blood loss, blood replaced, or wound hematoma formation. There was an unexplained increased mortality in the placebo group (21.1% vs. 2.0%, p = 0.033). CONCLUSIONS: Intraoperative bolus UK infusion is safe, with no significant fibrinogen depletion or increased operative blood loss or wound hematoma formation. Dose-related plasminogen activation resulted in significant breakdown in cross-linked fibrin in the distal circulation. Intraoperative bolus UK infusion may be valuable as an adjunct in patients with chronic occlusive disease who are undergoing revascularization. Detailed randomized studies are indicated to establish clinical efficacy. PMID- 8215645 TI - Techniques to enhance extramyocardial collateral blood flow after a cardiomyoplasty. AB - OBJECTIVE: Chronic stimulation of a cardiomyoplasty was combined with low-dose infusion of heparin into the arterial supply of the cardiomyoplasty in order to determine if latissimus-derived collateral blood flow could be further enhanced. SUMMARY BACKGROUND DATA: Acute and chronic stimulation of a latissimus dorsi cardiomyoplasty increased extramyocardial collateral blood flow to 35 +/- 9% and 27 +/- 5%, respectively, of normal myocardial blood flow. METHODS: A model of coronary artery disease was created with an ameroid constrictor in goats, and a cardiomyoplasty was performed. Heparin (15 to 50 U/h) was delivered into the left subclavian artery for a period of 4 weeks. Simultaneously, the latissimus dorsi was chronically stimulated at 2 Hz. RESULTS: Chronic ischemic myocardium received a collateral flow per gram from the skeletal muscle equivalent to 11.8 +/- 5.2% of the blood flow to normal myocardium. The extramyocardial collateral flow correlated with the latissimus muscle flow (r = 0.72). CONCLUSIONS: Enhancement of extramyocardial collateral flow was not found with heparin treatment. In view of the correlation of extra-coronary collateral flow with latissimus muscle flow, the lack of a heparin effect may have been due to low latissimus blood flow. These results suggest that extramyocardial collateral blood flow to the myocardium is highest if the blood flow to the latissimus dorsi muscle is maintained. PMID- 8215646 TI - Video-assisted thoracoscopic wedge resection of T1 lung cancer in high-risk patients. AB - OBJECTIVE: This study assessed the reliability and safety of VATR for treatment of peripheral T1 lung cancer in high-risk patients. SUMMARY BACKGROUND DATA: Surgical resection is the best therapy for stage I lung cancer. Patients with poor cardiopulmonary status or those who are elderly (> 75 years of age) are considered to be at high risk from thoracotomy and are frequently referred for radiation therapy or expectant palliative management. Data from previous studies suggest that survival with wedge resection is similar to that with lobectomy. The authors propose VATR, which is minimally invasive, as a therapeutic option in patients considered to be at high risk for resection by thoracotomy. METHODS: Between November 1990 and November 1992, more than 400 thoracoscopic lung resections were performed. Thirty patients with poor pulmonary function (forced expiratory volume FEV1] < 1 L or < 35% predicted; arterial oxygen tension [PaO2] < 60 mmHg on room air; diffusion capacity [DCO] < 40%) underwent 31 VATRs (1 patient had a staged procedure for bilateral synchronous lung cancers). All patients had T1 peripheral lesions with no bronchoscopically visible lesions. Computed tomography of the chest revealed no evidence of mediastinal disease in all patients. RESULTS: Patients had a mean FEV1 value of 0.9 L (38% predicted) and a mean age of 71 years. Tumors were located in left upper lobe (LUL) in 13 patients, in right lower lobe (RLL) in 7 patients, in right upper lobe (RUL) in 6 patients, in left lower lobe (LLL) in 4 patients, and in right middle lobe (RML) in 1 patient. Computed tomography-guided wire localization, methylene blue surface injection, and intraoperative ultrasonography were used to assist in defining difficult lesions. All lesions were successfully resected without converting to thoracotomy. One patient died on the 34th postoperative day of myocardial infarction (operative mortality rate of 3%). Five patients had prolonged air leaks (< 5 days), with a median chest tube time of 3 days. Two patients experienced pneumonia. CONCLUSION: The authors concluded that VATR is a safe and reliable procedure for treatment of peripheral T1 lung cancer in high risk patients. Long-term follow-up will be required to determine the efficacy of this procedure regarding survival and locoregional recurrence. PMID- 8215647 TI - Urological complications in 210 consecutive simultaneous pancreas-kidney transplants with bladder drainage. AB - OBJECTIVE: The urological complications of 210 patients who underwent simultaneous pancreas-kidney (SPK) transplantation over a 7-year period were reviewed. SUMMARY BACKGROUND DATA: Worldwide, bladder drainage has become the accepted method of exocrine drainage after pancreas transplantation. With the increasing use of bladder drainage, the surgical post-transplant complications have shifted from intra-abdominal complications to urological complications. METHODS: Two hundred ten diabetic patients received SPK transplants with bladder drainage. A retrospective review was conducted to analyze the incidence, type, and management of urological complications. RESULTS: The most frequent urological complications were hematuria, leak from the duodenal segment, recurrent urinary tract infections, urethritis, and ureteral stricture and disruption. Complications related to the renal transplant included ureteral stricture and leaks, as well as lymphoceles. CONCLUSIONS: Despite the high incidence of urological complications, 5-year actuarial patient and graft survival are excellent. Only one graft and one patient were lost secondary to urological complications. PMID- 8215648 TI - Improved survival with neoadjuvant therapy and resection for adenocarcinoma of the esophagus. AB - OBJECTIVE: This study sought to determine the impact of preoperative chemotherapy and radiation therapy (neoadjuvant therapy) followed by resection in patients with adenocarcinoma of the esophagus. SUMMARY BACKGROUND DATA: Long-term survival in patients with carcinoma of the esophagus has been poor. An increase in the incidence of adenocarcinoma of the esophagus has been reported recently. METHODS: Fifty-eight patients with biopsy-proven adenocarcinoma of the esophagus treated at this institution from January 1951 through February 1993 were studied. Since 1989, 24 patients were entered prospectively into a multimodality treatment protocol consisting of preoperative cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without etoposide, and concomitant mediastinal radiation (30 Gy). Patients were re-evaluated and offered resection. RESULTS: There were no deaths related to neoadjuvant therapy and toxicity was minimal. Before multimodality therapy was used, the operative mortality rate was 19% (3 of 16 patients). With multimodality therapy, there have been no operative deaths (0 of 23 patients). The median survival time in patients treated before multimodality therapy was 8 months and has yet to be reached for those treated with the neoadjuvant regimen (> 26 months, p < 0.0001). The actuarial survival rate at 24 months was 15% before multimodality therapy and 76% with multimodality therapy. No difference in survival was noted in neoadjuvant protocols with or without etoposide (p = 0.827). CONCLUSIONS: Multimodality therapy with preoperative chemotherapy and radiation therapy followed by resection appears to offer a survival advantage to patients with adenocarcinoma of the esophagus. PMID- 8215649 TI - Myocardial revascularization and porcelain aorta. PMID- 8215650 TI - Enzyme levels in shed blood after cardiac operations. PMID- 8215651 TI - Primary closure of infected sternum. PMID- 8215652 TI - Retrograde coronary sinus cardioplegia. PMID- 8215653 TI - Use of an arch balloon in cardiac surgery patients with severe peripheral vascular disease. PMID- 8215654 TI - Airway revascularization: is it necessary? PMID- 8215655 TI - Are arterial grafts better or worse than applied physiology teaches? PMID- 8215656 TI - Hypoperfusion after arterial bypass grafting. PMID- 8215657 TI - Five-year experience with the maze procedure for atrial fibrillation. AB - Between September 25, 1987, and December 31, 1992, 75 patients (53 men, 22 women; average age, 52 years) underwent the maze procedure for the treatment of atrial fibrillation. Six patients had undergone a previous cardiac operation and 28% underwent concomitant cardiac procedures in addition to the maze procedure. One patient (1.3%) died 10 days after undergoing a combined maze procedure and Morrow procedure for the management of chronic atrial fibrillation and hypertrophic obstructive cardiomyopathy. Postoperative atrial pacemakers were required in 40%: 26% for preoperative sick sinus syndrome and 6% for iatrogenic injury of the sinus node, and 8% had pacemakers in place preoperatively. As of December 31, 1992, 65 patients had been followed up for at least 3 months after operation (range, 3 to 63 months). The maze procedure cured atrial fibrillation, restored atrioventricular synchrony, and preserved atrial transport function in 64 of 65 patients (98%). The procedure has been curative without the need for medications in 58 of 65 patients (89%) and with the need for medications in 6 of 65 (9%), with medications failing in only 1 of the 65 patients (2%). The results support the maze procedure as the treatment of choice in patients with medically refractory symptomatic atrial fibrillation. PMID- 8215658 TI - Thoracoscopy for the diagnosis of the indeterminate solitary pulmonary nodule. AB - Traditional nonoperative diagnostic approaches to the indeterminate solitary pulmonary nodule include bronchoscopy and percutaneous needle biopsy. Although both methods are minimally invasive, the diagnosis of the small, peripheral nodule may remain elusive. Open thoracotomy is often required when these methods fail to obtain a diagnosis. Between January 1991 and June 1992, 242 patients with indeterminate solitary lung nodules underwent thoracoscopic excisional biopsy as the primary diagnostic method. Wedge excisions of the nodules were all performed by thoracoscopic techniques using an endoscopic stapler alone (72%), neodymium:yttrium-aluminum garnet laser (18%), or both (10%). A definite diagnosis was obtained in all patients. Two patients required conversion to thoracotomy to locate the nodule (both malignant). A benign diagnosis was obtained in 127 patients (52%) and a malignant diagnosis in 115 (48%). Of the malignant nodules, 51 (44%) were primary lung cancer and 64 (56%) were metastases. All patients diagnosed with primary lung cancer having adequate pulmonary reserve (n = 29) underwent formal open lung resection during the same procedure. There was no mortality, and significant morbidity was limited to atelectasis in 3 patients (1.2%), pneumonia in 2 patients (0.8%), and prolonged air leak more than 7 days in 4 patients (1.6%). Average hospital stay for patients having thoracoscopy only (n = 213) was 2.4 days (range, 1 to 12 days). Thoracoscopy offers a minimally invasive approach for the diagnosis of the indeterminate solitary nodule. It has advantages over traditional diagnostic methods of being virtually 100% sensitive and 100% specific with no mortality and minimal morbidity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215659 TI - Mid-term results after bidirectional cavopulmonary shunts. AB - Despite the increasing use of the bidirectional cavopulmonary shunt, little is known about the late results, the duration of palliation, and the frequency with which this procedure allows later successful conversion to a Fontan type of procedure. We reviewed our experience (1984 to 1992) in 38 consecutive children, ages 4 months to 16 years (mean, 4.0 years), who underwent a bidirectional cavopulmonary shunt procedure. All had a single functional ventricle and represented high risks for the performance of a Fontan procedure based on anatomic and hemodynamic criteria. The oxygen saturation in these patients improved from a preoperative value of 75% +/- 7% to 82% +/- 7% (p < 0.05) at late cardiac catheterization by a mean of 24 months after operation. The actuarial survival, including early deaths and that associated with all secondary procedures, was 86% at 1 year and 81% at 6 years. Early deaths occurred in 5.3% (2/38) and late deaths in 11% (4/36). Late follow-up ranged from 5 to 90 months (mean, 37 months). Conversion to a Fontan or fenestrated Fontan procedure was accomplished in 21 early survivors (21/36; 58%) by a mean of 26 months after the bidirectional cavopulmonary shunt procedure, with one operative and no late deaths (1/21; 4.8%). Three additional patients have undergone late reoperation, including 2 requiring cardiac transplantation and 1 undergoing the late creation of an axillary artery-to-vein fistula for the treatment of cyanosis. The midterm survival after a bidirectional cavopulmonary shunt procedure appears to be excellent, and it serves as a good staging procedure for patients who represent high risks for a Fontan procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215661 TI - Staged conversion to arterial switch for late failure of the systemic right ventricle. AB - Late failure of the systemic right ventricle is seen in up to 10% of patients after atrial switch for transposition of the great arteries and in patients with atrioventricular and ventriculoarterial discordance. Since 1981, 24 such patients have entered a program to achieve conversion to arterial switch. The primary diagnoses were transposition of the great arteries with ventricular septal defect (n = 10), transposition of the great arteries with intact ventricular septum (n = 5), Taussig-Bing anomaly (n = 4), and atrioventricular and ventriculoarterial discordance (n = 5). The mean interval from atrial switch to right ventricular failure was 7 years. Four patients underwent direct conversion to arterial switch, with one operative death. In 3 of these patients the initial left ventricular pressure was high. The fourth patient was too sick to undergo banding, and he required left ventricular assist device support after switch conversion. The other 20 patients underwent 34 procedures to place or tighten a pulmonary artery band to prepare the left ventricle to tolerate systemic pressure. There was one band-related operative death. Twelve patients have thus far gone on to switch conversion 13 days to 5 years (mean, 26 months) after banding. In total, therefore, 16 patients have had an arterial switch with atrial reconstruction. The early mortality for switch conversion was 2 of 16 (12.5%; 70% confidence limits, 4% and 27%), with one late death 12 months after operation. Including operative mortality, the 1-year actuarial survival probability after conversion was 80% (70% confidence limits, 62% and 92%). All survivors are asymptomatic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215660 TI - Transhiatal esophagectomy for carcinoma of the esophagus. AB - One hundred thirty-one patients (107 men and 24 women) underwent transhiatal esophagectomy for carcinoma of the esophagus. Median age was 65.3 years (range, 30 to 89 years). Signs and symptoms were present in 130 patients, which included dysphagia in 96 (73.3%) and weight loss (median, 7.7 kg) in 52 (39.7%). The cancer involved the gastroesophageal junction in 94 patients, the lower half of the intrathoracic esophagus in 25, the upper half in 10, and multiple sites in 2. An adenocarcinoma was present in 101 patients (77.1%), squamous cell carcinoma in 29 (22.1%), and adenosquamous cell in 1 (0.8%). The cancer was classified as stage 0 in 4 patients, stage I in 16, stage IIA in 26, stage IIB in 18, stage III in 65, and stage IV in 1. The stomach was used to replace the esophagus in all patients. Operative mortality was 2.3%. Anastomotic leak developed in 32 patients; 6 leaks were not clinically significant, 12 healed with drainage alone, and 14 required further surgical intervention. Follow-up ranged from 1 month to 6.7 years (median, 1.4 years). Currently, 42 patients are alive, 34 without evidence of recurrence. Overall 5-year survival was 20.8% and varied according to stage. Five-year survival was 47.5% for patients with stage I disease compared with 37.7% for patients in stage II and only 5.8% 4-year survival for patients in stage III. Cell type also influenced survival. Five-year survival for patients with adenocarcinoma was 27.1% compared with zero for patients with squamous cell carcinoma (p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215662 TI - Accuracy of lung imaging in metastases with implications for the role of thoracoscopy. AB - Thoracoscopy for wedge resection of lung metastases is rapidly increasing in frequency. This technique precludes bimanual palpation of the lung to locate additional lesions not seen on the surface. Finger palpation is inadequate. Implications regarding the failure to identify all metastases and the negative impact on long-term survival led us to review retrospectively the correlation between pathologic findings and imaging reports. One hundred forty-four patients who had resection of lung metastases from colorectal cancer were studied. All had chest roentgenograms and 72 had computed tomographic scans as well. Chest roentgenogram and computed tomographic reports differed in the number of nodules reported in 17 of 72 patients (24%). In 3 of 17 patients chest roentgenogram showed more nodules than computed tomography. Chest roentgenogram differed from pathologic findings at surgery in 57 of 144 patients (39%). Twenty-six of 57 patients (46%) had more lesions than chest roentgenogram detected and 31 had fewer. Computed tomographic scans differed from pathologic findings in 30 of 72 patients (42%). If one or two lesions were imaged, 12 patients had fewer cancers (some lesions were benign) and 18 had more cancers than computed tomography reported; computed tomographic scans erred 28% of the time. The inability to adequately palpate the entire lung using the thoracoscope alone markedly impairs the surgeon's ability to know if a resection of all lesions has been done. The validity of using thoracoscopy resection in the management of metastatic disease is seriously questioned other than for diagnosis. PMID- 8215663 TI - Girdling effect of nonstimulated cardiomyoplasty on left ventricular function. AB - The precise hemodynamic effects of latissimus dorsi cardiomyoplasty have not been well characterized. We prospectively studied 11 mongrel dogs using a rapid ventricular pacing model of congestive heart failure. Six dogs received a nonstimulated left latissimus dorsi cardiomyoplasty wrap, and 5 control dogs were paced only. Two-dimensional transthoracic echocardiography was performed on all dogs at baseline and then weekly for 4 weeks. Measurements obtained included left ventricular diameters, lengths, volumes, and ejection fractions. Progressive left ventricular enlargement, increase in volumes, and worsening ejection fractions developed in both groups. However, less left ventricular dilatation and higher ejection fractions were seen in dogs that received a cardiomyoplasty wrap. A nonstimulated cardiomyoplasty wrap significantly attenuated the degree of left ventricular enlargement, increase in left ventricular volumes, and decrease in ejection fraction in a rapid pacing model of congestive heart failure. Apart from its effect on systolic augmentation with a stimulated muscle wrap, cardiomyoplasty may have an important "girdling" effect on the left ventricle that prevents dilatation and deterioration of left ventricular function. PMID- 8215664 TI - Esophagectomy in the septuagenarian. AB - As the population continues to age, older patients are being referred for thoracic surgical procedures with increasing frequency. From 1985 through 1992, 38 patients (32 men, 6 women) 70 years of age or older underwent esophagectomy for primary esophageal carcinoma. Histologic findings included adenocarcinoma in 28 (74%) and squamous carcinoma in 10 (26%). Patients suffered dysphagia for a mean of 3.8 months (range, 0 to 30 months) and had a mean weight loss of 5.8 kg (range, 0 to 22 kg). The tumors ranged from 1 to 14 cm in length and averaged 4.7 cm. Preoperative chemotherapy and radiation therapy were administered in 11 patients (46%). Clinical staging suggested all patients were curable, and esophagectomy was performed in a transthoracic fashion in 27 (71%) and from a transhiatal approach in 11 (29%). Cervical anastomoses were undertaken in 16 patients (42%). The mean blood loss was 1,165 mL and ranged from 500 to 4,000 mL. The mean number of transfused units was 2.3 (range 0 to 8 U). Overall operative mortality was 18% (7 of 38). Major morbidity included pneumonia in 11 (29%), anastomotic leak in 4 (11%), chylothorax in 4 (11%), pulmonary embolus in 3 (8%), and stroke and myocardial infarction in 1 patient each (3%). Three patients have been cured of their esophageal cancer with survivals of 65, 70, and 72 months and an additional 7 patients are still alive. Three patients (8%) have been lost to follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215665 TI - Successful double-lung transplantation with direct bronchial artery revascularization. AB - Double-lung transplantation with tracheal anastomosis has previously resulted in unacceptable ischemic complications of airway healing. Three patients underwent double-lung transplantation at our institution in 1986 and 1987, and 2 of these required later retransplantation because of airway complications. Recently, we began to perform direct revascularization of the bronchial arteries at their origin on the donor descending thoracic aorta, using recipient internal thoracic artery. Eight patients (2 male and 6 female patients; ages, 10-51 years) underwent nine double-lung transplantations with revascularization. The preoperative diagnoses in these patients were cystic fibrosis (2 patients), atrial septal defect and Eisenmenger's syndrome (1 patient), lymphagioleiomyomatosis (1 patient), bronchiectasis (1 patient), alpha 1 antitrypsin deficiency (1 patient), and primary pulmonary hypertension (2 patients); 1 underwent retransplantation because of pulmonary emboli. There have been no significant airway complications in any patient. Two patients died early postoperatively, 1 of early pulmonary dysfunction (at 1 day postoperatively) and 1 of subarachnoid hemorrhage (at 16 days postoperatively; tracheal healing was excellent in this patient). Follow-up in the remaining 6 patients ranged from 5 to 9 months. Internal thoracic artery angiography was performed on seven grafts, which documented patency of the internal thoracic artery in all seven and bronchial artery perfusion in six. Bronchoscopic examinations have demonstrated excellent airway healing in all six of these grafts, with no dehiscence, granulation, or narrowing of the trachea or distal bronchi. Ulceration of the tracheal anastomosis developed anteriorly in the remaining patient, which has resolved. We conclude that double-lung transplantation is an acceptable therapeutic approach when combined with bronchial artery revascularization, and early airway healing has been excellent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215666 TI - Different anticoagulants and platelet reactivity in cardiac surgical patients. AB - A technique for assessing platelet reactivity to shear stress from nonanticoagulated blood samples was employed to compare the relative effects of an unfractionated heparin, a low-molecular-weight heparin, and hirudin. The in vitro platelet effect of unfractionated heparin (5 U/mL) was measured in 290, the effect of a low-molecular-weight heparin (1 anti-Xa unit/mL) in 74, and the effect of hirudin (8 micrograms/mL) in 50 cardiac surgical patients. The relative proportions of patients exhibiting an enhanced platelet reactivity, a mild to moderate inhibition, and a severe inhibition were, respectively: 8.6%, 58.6%, and 32.8% for unfractionated heparin; 22%, 66%, and 12% for the low-molecular-weight heparin; and 6%, 66%, and 28% for hirudin. At the concentrations examined, a significantly greater proportion (p < 0.01) of the patients exhibited enhanced platelet reactivity and a significantly smaller proportion (p < 0.01) showed severely inhibited platelet reactivity associated with the low-molecular-weight heparin versus the unfractionated heparin, whereas there was no significant difference between the patients treated with hirudin and unfractionated heparin. Although the relevance of this study is limited because the clinically appropriate concentration of the alternative anticoagulants and comparative doses are unknown, it can be inferred that low-molecular-weight heparin may reduce the blood loss associated with cardiopulmonary bypass. PMID- 8215667 TI - Thoracoplasty in the context of current surgical practice. AB - Although widely employed for well over a century as a procedure for reducing the capacity of the thoracic cavity, thoracoplasty in current practice has become a rarity. A retrospective analysis of 37 patients (29 men, 8 women) who underwent the procedure under the care of one thoracic surgeon in a 16-year period provides the basis for this presentation. Ages ranged from 23 to 82 years with a mean age of 58 +/- 12.8. The mean follow-up was 8.5 years. Nineteen patients underwent the procedure for complications after lung resection for lung cancer. There were four perioperative deaths in this group (21.1%) and 6 long-term survivors (31.6%). Eighteen patients without lung cancer underwent thoracoplasty as a planned treatment or for complications. There were no perioperative deaths, two late deaths, and 16 long-term survivors (88.9%) in the group. In the entire series, the overall perioperative mortality rate was 10.8% with no major long-term morbidity. Although proper timing and proper patient selection are essential in the use of thoracoplasty as a procedure to cope with the septic complications of lung cancer resection, it is overall a safe and successful procedure that has a relatively low mortality and that leads to considerable improvement in quality of life. PMID- 8215668 TI - Biophysical properties of the gelatin-resorcin-formaldehyde/glutaraldehyde adhesive. AB - Refixation of dissected aortic layers with gelatin-resorcin formaldehyde/glutaraldehyde (GRFG) adhesive represents a new option in the surgical treatment of aortic dissection. Because of its ability to reinforce the delicate structures of the acutely dissected aortic wall, GRFG has been used increasingly in recent years. However, the biomechanical properties of the adhesive are still unclear, and little is known regarding the optimal mode of its application. In an ex vivo study, aortic specimens from sheep were glued with warm (45 degrees C) adhesive under wet and dry conditions and submitted to defined degrees of compression (5 Newtons [N], 20 N). Bonded specimens were retracted to assess tensile strength and elasticity compared with two reference adhesives: cyanoacrylate gel and fibrin glue. Gelatin-resorcin formaldehyde/glutaraldehyde and cyanoacrylate gel showed similar results at 5 N. Both provided better adhesion when applied under dry conditions (GRFG 5 N: dry, 3.5 +/- 1.6 N/cm2; wet, 1.4 +/- 1.0 N/cm2; cyanoacrylate gel 5 N: dry, 4.8 +/- 1.8 N/cm2; wet, 3.2 +/- 1.3 N/cm2). At 20 N, GRFG tensile strength was significantly increased for either condition compared with values at 5 N (GRFG 20 N: dry, 17.1 +/- 4.2 N/cm2; wet, 4.8 +/- 1.8 N/cm2). Fibrin glue demonstrated only weak adhesive properties even under dry conditions (fibrin glue 5 N: dry, 0.8 +/- 0.3 N/cm2). Gelatin-resorcin-formaldehyde/glutaraldehyde has good adhesive properties both in wet and dry tissue. Bonding capacity can be substantially increased when applied on dry surfaces and at increased pressures. PMID- 8215669 TI - Antibiotic prophylaxis in cardiac operations. AB - This clinical trial, which was composed of 1,031 adults undergoing cardiac operations, compared the efficacy of a single dose of 1 g of ceftriaxone with a 48-our regimen consisting of flucloxacillin and gentamicin. There was no significant difference (p = 0.89) in the overall incidence of major infections: 30 of 515 patients (5.8%; 95% confidence interval, 5.4% to 6.2%) taking ceftriaxone and 29 of 516 patients (5.6%; 95% confidence interval, 5.2% to 6.0%) taking flucloxacillin and gentamicin. Subgroup analyses, with a lower statistical power, failed to show a significant difference between patients who received ceftriaxone and those who received flucloxacillin/gentamicin: major sternal wound infections arose in 2.7% of the patients taking ceftriaxone versus 1.6% in those on the 48-hour regimen (p = 0.20) and major limb wound infections arose in 4.2% and 5.4%, respectively (p = 0.44). Single-dose prophylaxis was associated with fewer intravenous administrations (864 doses versus 9,570 doses) and cost less (A$17,248 versus A$78,510). Although the regimen that included gentamicin was associated with the greatest biochemical impairment of renal function, the overall toxicity for both groups was low. We conclude that a single dose of ceftriaxone provided cost-efficient prophylaxis for adults undergoing cardiac operations when compared with a 48-hour regimen of gentamicin and flucloxacillin. The general principle revealed by our data is that the short-term administration of an appropriate antibiotic regimen represents optimal prophylaxis for patients undergoing cardiac procedures. PMID- 8215670 TI - Closure of bronchial defects using a pedicled pericardial flap. AB - A technique for closure of lateral or terminal defects in the bronchial wall after tissue-saving procedures, which obviates the need for sleeve resection in few selected situations, is described. Its main advantages are a low risk of surgical complications at the suture line and easy performance. PMID- 8215671 TI - Mitral valve Carpentier-Edwards bioprosthetic replacement, thromboembolism, and anticoagulants. AB - Patients undergoing mitral valve replacement (MVR) using a bioprosthesis are frequently placed on long-term anticoagulant treatment, and thereby lose the main advantage conferred by the bioprosthesis. To assess predictive factors of the need for long-term anticoagulant treatment, 100 consecutive patients surviving bioprosthetic MVR between 1977 and 1987 were followed up. The estimated thromboembolism-free survival was 88.9% +/- 3.6% after 6 years of follow-up. Preoperative risk factors for thromboembolism were supraventricular arrhythmia (p = 0.013) and a history of thromboembolism (p = 0.039). Among the preoperative and postoperative factors, only postoperative rhythm significantly influenced (p = 0.007) the thromboembolism-free survival, as determined by Cox regression analysis. Permanent anticoagulant treatment was instituted in 39 patients. Preoperative and peroperative risk factors associated with the need for long-term anticoagulant treatment, as evidenced by Fisher linear discriminant analysis, were supraventricular arrhythmia (p < 0.001), septal myotomy (p = 0.013), and predominant mitral stenosis (p = 0.013). Thus, in those patients with predominant mitral stenosis and supraventricular arrhythmia preoperatively, the subsequent need for permanent postoperative anticoagulant treatment is high, and the implantation of a mechanical valve is therefore recommended, providing there are no strict contraindications to anticoagulant treatment. PMID- 8215672 TI - Comparison of three blood-processing techniques during and after cardiopulmonary bypass. AB - The return of extracorporeal circuit blood at the termination of cardiopulmonary bypass is an important feature of blood conservation during open heart procedures. However, the relative benefits and disadvantages of different circuit blood salvage methods remain unclear. Accordingly, the purpose of this study was to examine whether quantifiable differences exist between three different circuit blood-salvaging techniques: direct infusion, centrifugation, and ultrafiltration. Sixty patients with very similar preoperative characteristics were randomly assigned to each of the three groups, and blood coagulation screens, plasma profiles, and respiratory function were determined at 20 minutes and at 6 and 18 hours after cardiopulmonary bypass. Early after cardiopulmonary bypass (20 minutes), the plasma colloid osmotic pressure and fibrinogen and platelet concentrations were significantly higher with ultrafiltration (p < 0.05) versus those observed for the other two methods. The plasma thromboplastin times were significantly (p < 0.05) longer after cardiopulmonary bypass with centrifugation as compared to direct infusion and ultrafiltration. However, the coagulation profiles and plasma composition normalized by 18 hours after cardiopulmonary bypass with all three blood-salvaging methods. There were no significant differences in terms of blood utilization or chest tube drainage over the entire postoperative period among any of the circuit blood-salvaging methods. These results suggest that ultrafiltration of postcardiopulmonary circuit blood may preserve plasma colloid pressure and platelet concentration in the early postoperative period, but these differences do not persist. Thus, for routine cardiopulmonary bypass procedures, direct infusion, centrifugation, and ultrafiltration may all be satisfactory methods of circuit blood salvage. PMID- 8215673 TI - Physiologic characteristics of coronary artery bypass grafts. AB - To investigate the hemodynamic characteristics of arterial grafts for coronary artery bypass grafting, we measured phasic pressure and flow patterns in three types of grafts in a canine model (n = 18). A graft from the ascending aorta (AAG), a graft from the descending aorta at the first lumbar level (DAG), analogous to a right gastroepiploic artery, and an internal thoracic artery (ITA) were anastomosed to each other. The composite graft was anastomosed to the left anterior descending coronary artery, and then the left anterior descending coronary artery was ligated. Before grafting, the AAG showed high sustained diastolic pressure, but the ITA and DAG showed rapid fall of diastolic pressures. Mean diastolic pressures were 83 +/- 2, 72 +/- 3, and 57 +/- 2 mm Hg in the AAG, ITA, and DAG (p < 0.05). Free flow in the AAG was markedly greater than in the ITA or the DAG. After grafting to the left anterior descending coronary artery, no changes were observed in diastolic pressures compared with the pregrafting values. Total blood flows were 72 +/- 6, 80 +/- 7, 57 +/- 7, and 44 +/- 6 mL/min in the left anterior descending coronary artery, AAG, ITA, and DAG, respectively. There were no differences in systolic graft flow between the three types of grafts. Diastolic blood flow in the ITA (29 +/- 4 mL/min) and DAG (18 +/- 3 mL/min) was smaller than in the AAG (48 +/- 4 mL/min) (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215674 TI - Flow capacities of arterial grafts for coronary artery bypass grafting. AB - The flow capacities of arterial and saphenous vein grafts in 100 patients who had coronary artery bypass grafting were compared under exercise conditions by continuous ventricular function monitoring, which records serial beat-to-beat radionuclide data and calculates left ventricular ejection fractions every 20 seconds. Ejection fraction profiles during graded bicycle exercise were divided into four types. In type A, the ejection fraction continued to increase. In type B, the ejection fraction initially increased, but decreased during the late exercise stage. In type C, the ejection fraction did not change. In type D, the ejection fraction continued to decrease throughout exercise. A decrease in ejection fraction, observed in type B or D, is an early indicator of myocardial ischemia. Before operation, 10 patients showed type A, 30 type B, 11 type C, and 49 type D responses. After operation, 68 patients showed type A, 21 type B, and 11 type C responses. Patients were divided into three groups according the type of bypass graft. Group 1 included 21 patients with two arterial grafts and vein grafts; group 2, 61 patients with an internal thoracic artery graft and vein grafts; group 3, 18 patients with only vein grafts. All of the grafts were patent on angiography. Eight patients (38%) in group 1 and 13 (21%) in group 2 showed a postoperative type B response, but none of the patients in group 3 had a postoperative type B response (p < 0.02). Seven of 8 patients in group 1 with postoperative type B responses had only arterial grafts to the left-side coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215675 TI - Total cavopulmonary direct anastomosis: a logical approach in selected patients. AB - A 2.5-year-old boy with a diagnosis of situs solitus, tricuspid atresia, anatomically corrected malposition of the great arteries (S,D,L), left juxtaposition of atrial appendages, and pulmonary stenosis underwent successful total cava-to-pulmonary connection by means of a superior vena cava-to-pulmonary artery end-to-side anastomosis associated with an inferior vena cava-to-pulmonary artery direct anastomosis. Anatomic features and surgical technique are described. PMID- 8215676 TI - Primary B-cell malignant lymphoma of the lung. AB - A 52-year-old asymptomatic man was evaluated for two right lung lesions discovered on a chest roentgenogram during a routine physical examination. A computed tomographic scan revealed the absence of mediastinal nodal involvement. Guided-needle aspiration cytology was inconclusive. A subsequent right thoracotomy was necessary to perform biopsy of these masses, which proved to be B cell malignant lymphomas of the lung. This case represents a rare example of a primary low-grade B-cell pulmonary lymphoma of mucosa-associated lymphoid tissue, with its distinct clinicopathologic features. PMID- 8215677 TI - Dacron aorta. AB - During the span of 6 years a 67-year-old woman underwent four consecutive major aortic operations, ultimately replacing her entire thoracoabdominal aorta with the exception of a tiny segment from which the left subclavian artery originated. The relatively uneventful postoperative course with each operation (one emergency and three elective procedures) and her current satisfactory condition at age 73 years have been attributed to her physical and mental fortitude, excellent anesthesia, superb postoperative care, and the chronic nature of her segmental aortic lesions caused by arteriosclerosis. PMID- 8215678 TI - Perforation of the esophagus by a fish bone leading to cardiac tamponade. AB - A 32-year-old woman swallowed a fish bone and presented to the hospital 3 days later with chest pain and fever. While in the hospital, she became hypotensive. A computed tomographic scan showed a fish bone penetrating from the esophagus into the pericardium. The fish bone was removed at urgent thoracotomy with immediate relief of her circulatory compromise. At the time of the operation, the fish bone was noted to be abrading the surface of the left atrium. We report this case of cardiac tamponade secondary to a perforated esophagus after foreign body ingestion. PMID- 8215679 TI - Cardiac dilatation after cardiopulmonary bypass: ceramic plate technique for sternal splinting. AB - Intraoperative sternal closure after cardiopulmonary bypass in patients with cardiac dilatation and dysfunction may cause fatal deterioration of their hemodynamics. To avoid this complication, a ceramic plate made from methyl methacrylate was used for sternal splinting. This simple splint can avoid chest wall compression to the overdilated heart, maintaining stable hemodynamics after cardiopulmonary bypass without postoperative respiratory complications or mediastinal infection. PMID- 8215680 TI - Sequential bilateral lung transplantation for pulmonary alveolar microlithiasis. AB - Lung transplantation has been successfully used in the treatment of patients with end-stage pulmonary disease and adequate cardiac function. We report about a 32 year-old man with pulmonary alveolar microlithiasis who underwent sequential bilateral lung transplantation. Preoperative hemodynamic studies revealed severe pulmonary hypertension; the right ventricular ejection fraction was 0.27. Eighteen months postoperatively, he continues to do well with normalized pulmonary and cardiac function and without clinical or histopathologic signs of graft rejection. PMID- 8215681 TI - Right gastroepiploic artery used as a pedicled graft in a retrograde fashion. AB - The right gastroepiploic artery is currently regarded as a most valuable arterial conduit for myocardial revascularization. We have documented a particular case wherein the proximal (pyloric) part of the right gastroepiploic artery could not be freed and was damaged because of previous cholecystectomy. The pedicle was divided at the pyloric side and raised up to be anastomosed to the posterior descending artery in a retrograde fashion. The purpose of this report is to emphasize the fact that a previous abdominal operation does not necessarily hamper the use of the gastroepiploic artery as a pedicled graft. It is also pointed out that retrograde flow in the pedicle was sufficient in this case to provide good revascularization. PMID- 8215682 TI - Chronic type A aortic dissection: an unusual complication of cocaine inhalation. AB - Acute aortic pathology temporally related to cocaine inhalation may lead to frank rupture or acute aortic dissection. This is a report of an unusual case of a 43 year-old man who presented 9 weeks after experiencing a tearing sensation in his chest while smoking cocaine. The diagnosis was chronic type A aortic dissection with 4+ aortic insufficiency. The successful surgical management included resuspension of the aortic valve and placement of a Dacron tube graft in the ascending aorta such that flow was maintained distally in both the true and false lumens. PMID- 8215683 TI - Staged repair of pentalogy of Cantrell with tetralogy of Fallot. AB - We report a successful two-stage repair of tetralogy of Fallot associated with pentalogy of Cantrell. The first stage, performed in the neonatal period, consisted of repairing the omphalocele, separating the peritoneal from the pericardial cavities, and covering the heart. The second stage, performed at 6 years of age, consisted of complete intracardiac repair and placing the heart in the chest. The patient is alive and well 18 months after the operation. PMID- 8215684 TI - Retrograde vital organ perfusion during aortic arch repair. AB - A technique is described for cerebral and other vital organ preservation during aortic arch repair using retrograde venous perfusion at 20 degrees C. This technique retains the excellent operating conditions of deep hypothermia and circulatory arrest. Potential benefits include shortening of the cooling and rewarming time, reduction of coagulopathy, prevention of emboli, and extension of the safe period of antegrade circulatory arrest. PMID- 8215685 TI - Prevention of retrograde cardioplegia catheter displacement. AB - The most frequent catheter-related complication of retrograde cardioplegia, in our experience, has been catheter displacement. An easily placed coronary sinus snare that maintains proper retrograde catheter position is described. PMID- 8215686 TI - Aorto-aortic shunt via the left ventricular apex for operation on the distal arch and the descending aorta. AB - A technique of aorto-aortic shunt using ordinary non-heparin-bound tubing was used in 21 patients. The proximal limb of the shunt was introduced via the left ventricular apex and advanced through the aortic valve into the ascending aorta, thereby avoiding the difficulty of cannulating the ascending aorta and offering a superior alternative to positioning the proximal limb in the left ventricular cavity. PMID- 8215687 TI - Hugh Morriston Davies: first dissection lobectomy in 1912. AB - Hugh Morriston Davies (1879-1965), long before anybody else, performed the first anatomic dissection lobectomy for a tumor of the lung in 1912. By replacing the hilar mass-ligation-suture technique, he was decades ahead of his time, and had his patient not died 8 days after the operation, he would have preceded Evarts Graham's first lung resection for cancer by 21 years! An all-around chest physician and surgeon in one, he had introduced chest radiography and positive pressure intratracheal anesthesia the year before, thus making the diagnosis and operation of this lung cancer possible. He concluded that lung cancer was accessible to surgical removal on condition of an early diagnosis. By destiny a surgeon as well as a physician, Morriston Davies was probably the earliest advocate of interdisciplinary teamwork in thoracic medicine. PMID- 8215688 TI - Lung preservation: a review of current practice and future directions. AB - During the past 10 years, pulmonary transplantation has emerged as a successful mode of surgical therapy for suitable patients with end-stage lung disease. Current preservation techniques of donor lungs for subsequent transplantation include core-cooling and single flush perfusion. The relative merits of these are described. These methods are essentially restricted to 6 hours of ischemia. Research in lung preservation is aimed not only at extending the safe period of ischemia but also at improving the quality of preservation. Areas of interest include the ideal composition of the perfusate, relevant pharmacologic additives, and the best conditions for preservation and harvesting. Advantages and disadvantages of the various animal models are listed in addition to the methods used in assessing the quality of preservation. There have been major advances in experimental lung preservation during the past 10 years, and we are possibly on the threshold of incorporating some of these into clinical practice. Among the most important are the adoption of colloid-based perfusates, the more widespread use of free radical scavengers, and the use of leukocyte depletion. PMID- 8215689 TI - Risk factors for unexplained dyspermia in infertile men: a case-control study. AB - This study was conducted to analyze risk factors for dyspermia in infertile subjects in a population of men attending outpatient services for infertility in Milan, Northern Italy. Between September 1989 and November 1990 we conducted a case-control study on risk factors for dyspermia. Cases included infertile men with a diagnosis of unexplained dyspermia consecutively observed for the first time during the study period at the Outpatient Service for Infertility of the First Obstetric and Gynecologic Clinic of the University of Milan. Specific work up was done to exclude the major known or potential causes of dyspermia and infertility in patients and their partners. Two control groups were selected. The first included normospermic men of infertile couples with negative work-up for any disease that might affect fertility, observed in the same outpatient service where cases had been identified. The second control group included fertile men of unknown semen quality who were the partners of women who gave birth at term (> 37 w gestation) to health infants in randomly selected days at the same clinic. In comparison with those who have never smoked, current smokers were at increased risk of dyspermia versus both normospermic men of infertile couples and fertile men of unknown semen quality, and the risk increased with number of cigarettes smoked per day and duration of smoking. The risk of dyspermia increased with the number of cups of coffee drunk per day compared with men drinking no or one cup per day. Likewise, alcohol drinkers were at increased risk and the risk increased with number of drinks/d.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215690 TI - Hormone profiles and testicular histology in azoospermic men with sex chromosome aberrations, autosomal anomalies and normal karyotype. AB - Hormone profiles and testicular histology were studied in azoospermic men with sex chromosome aberrations, autosomal anomalies, and normal karyotype. In patients with sex chromosome aberrations, levels of plasma gonadotropins were significantly higher than those with autosomal anomalies and normal karyotype. The testosterone level in plasma was considerably lower in those with sex chromosome aberrations than in other groups. The prolactin level in plasma was not significantly different among the three groups. The administration of LH-RH resulted in a remarkably lower response of plasma gonadotropins in sex chromosome anomalies than in other groups. The response of plasma testosterone to the administration of hCG was also significantly decreased in those with sex chromosome aberrations compared with other groups. Johnsen score count and diameter of the seminiferous tubules were considerably reduced in those with sex chromosome anomalies compared with other groups, while wall thickness and Leydig cells per seminiferous tubule were significantly increased. It would appear that hormone disturbances and testicular alterations are less marked in azoospermic men with autosomal anomalies than in those with sex chromosome aberrations. PMID- 8215691 TI - Failure of the addition of fresh seminal plasma to cryopreserved-thawed sperm to improve semen parameters. AB - Previous data has shown that subnormal motility in some semen specimens can be improved by the addition of fresh human seminal plasma (HSP). However, if the HSP was first frozen the motility-enhancing factor was lost. We hypothesized that some of the reduction in sperm motility of cryopreserved-thawed sperm may be related to damage of the "motility-enhancing factor" of HSP. This study evaluated whether the addition of fresh HSP could improve the motility of frozen-thawed sperm. Each frozen-thawed specimen was evaluated for motile density and hypoosmotic swelling and then divided into two aliquots. Equal volumes of HSP, human tubal fluid (HTF), and control media were added and the semen parameters were reevaluated. The mean scores for motile density and percent motility did not change compared with baseline thawed volumes with either HSP or HTF additives. There were some isolated cases that did improve with either HSP (21%) or HTF (14%). Future studies are needed to determine whether this improvement is coincidental or consistent, and to determine whether at least some individuals can benefit from the addition of fresh HSP to frozen-thawed sperm. PMID- 8215692 TI - Effect of semen characteristics on pregnancy rate in a gamete intrafallopian transfer program. AB - The aim of this study was to evaluate the influence of sperm morphology, swim-up concentration, and insemination volume on pregnancy outcome in patients undergoing gamete intrafallopian transfer (GIFT) treatment in whom the male partner had a morphology of less than 14%. Only patients who received four oocytes were entered into this study (n = 103). In all cases the swim-up procedure time was standardized to 1 h and the insemination concentration was standardized to 500,000 per oviduct. There was no significant difference in pregnancy rate when normal morphology, swim-up concentration, or insemination volume were used as predictors. In the P pattern group (< 4% normal forms) only four of the 28 (14%) patients had ongoing pregnancies, whereas in the G pattern group (5% to 14% normal forms) 16 out of 75 (21%) had ongoing pregnancies (P vs G, p > 0.05; not significant). The fertilization rate among excess oocytes in the P pattern group was 18% but was 39% (p < .0001) in the G pattern group. When an attempt was made to compensate for low morphology by increasing insemination concentration no significant difference in the pregnancy rate between the P and G pattern groups in the GIFT program was recorded. This was not the case when the in vitro fertilization rate was used as an endpoint. Insemination volume and swim up concentration played no role in pregnancy rate. PMID- 8215693 TI - Role of the cumulus in the selection of morphologically normal sperm and induction of the acrosome reaction during human in vitro fertilization. AB - This study analyzed the role that the cumulus oophorus may play in the selection of morphologically normal sperm and the induction of the acrosome reaction. Using the triple stain technique, sperm morphology and acrosomal status were compared between sperm that penetrated the cumulus during in vitro fertilization and sperm from outside the cumulus. The mean percentage of morphologically normal sperm in the samples was 54 +/- 2.8 and increased (p < 0.05) to 67 +/- 2.6 within the cumulus. Tapered sperm were significantly decreased (p < 0.05) within the cumulus. The percentage of sperm undergoing the acrosome reaction significantly increased (p < 0.05) from 14.5 +/- 1.5 to 24.5 +/- 1.9 when incubated with a cumulus mass, and further increased to 49 +/- 3.3 when incubated with mature, expanded cumulus tissue containing an oocyte. These data indicate that human cumulus oophorus plays an active role in the selection of morphologically normal sperm, and influences the ability of the sperm to undergo the acrosome reaction. PMID- 8215694 TI - Changes in seminal plasma transferrin concentration following administration of clomiphene citrate. AB - This study was designed to investigate the functional changes in Sertoli cells following clomiphene citrate administration to patients with idiopathic infertility. The agent was administered to 44 oligozoospermic patients. Patients with improvement in sperm concentration after treatment (improvement group) showed significantly lower pretreatment follicle-stimulating hormone (FSH) levels in serum. Serum FSH and testosterone levels significantly increased in the improvement group after treatment (both p < 0.05). Seminal transferrin concentration significantly increased in the improvement group after treatment (p < 0.05), although there was no significant difference between pretreatment seminal transferrin concentration in the improvement group and that in patients with no improvement in sperm concentration. Seminal plasma transferrin concentration in patients in whom pretreatment luteinizing hormone level in serum was below 10 mIU/mL, and in those in whom the ratio of post- to pretreatment values was 1.5 or more, tended to increase after treatment. This group also contained a few more patients with improvement in sperm concentration than the other groups. The patients showing low pretreatment FSH levels and a high ratio of post- to pretreatment values demonstrated a significant increase in seminal plasma transferrin concentration after treatment (p < 0.01), and this group contained more patients with improvement than the other groups. It would appear that Sertoli cell stimulation may induce an increase in sperm concentration after clomiphene citrate administration, and the elevated transferrin secretion seems to be associated with the increase of serum FSH level after treatment. PMID- 8215695 TI - In vitro interaction between oviduct epithelial and equine sperm. AB - Coculture of stallion sperm with monolayers of equine oviductal epithelial cells (OEC) was evaluated. Monolayers were obtained from frozen-thawed OEC. Live sperm attached to the OEC in vitro, whereas sperm killed by heat treatment or glutaraldehyde fixation did not. Sperm attached to OEC showed flagellar motion for 4 d in vitro, during which time they gradually became released. Scanning electron-micrographs showed an intimate association between the sperm and OEC. Incubation of sperm for 4 h with either control, heparinized or OEC-conditioned medium (Tyrode's albumin lactate phosphate) resulted in more incapacitated sperm, as determined by chlortetracycline staining patterns. The OEC-conditioned medium caused similar capacitation-like changes to those seen with heparin. Sperm viability as determined by Hoechst 33258 staining was not significantly affected by media type. PMID- 8215696 TI - Sexually transmitted diseases and related genital pathologies in oligozoospermia. AB - Sexually transmitted pathogens are associated with a wide range of anomalies and diseases, including recurrent genital herpes, urethritis, syphilis, prostitis, genital ulcers, perihepatitis, unexplained infertility, infant prematurity, low birth weight, and neonatal death or malformations. Prompt diagnosis of sexually transmitted diseases (STDs) is essential to ensure appropriate specific treatment and to reduce complications. Extensive studies on the etiology of male infertility include poorly treated infections such as STDs, epididymitis, complications associated with mumps, delayed treatment of undescended testes, repair of inguinal hernia, varicocele, endocrine disorders, anomalies of the reproductive tract and male accessory organs, trauma, surgery, heat-cold injury, and active-passive immunization. PMID- 8215697 TI - Nonspermatozoal cells in semen: relationship to other semen parameters and fertility status of the couple. AB - In semen samples from 94 men from infertile couples and 42 control patients proven to be fertile the occurrence of different kinds of nonspermatozoal cells (NSC) was examined. The findings were evaluated in relation to other seminal parameters and to the fertility status of the couple. The ratios of NSC to sperm and primary spermatocytes to spermatids revealed increasing values with decreasing sperm counts. Especially in a group where the semen samples contained > or = 6 x 10(6) motile sperm per mL and no infertility factor was detectable in the woman, the concentration of leukocytes was high, with three of eight patients having > or = 10(6) leukocytes per mL. A high proportion of abnormal sperm seemed to occur more frequently where the cause of infertility could be found in the man. A high number of leukocytes was neither significantly associated to an increased proportion of abnormal sperm nor to sperm motility evaluated by recording the percentage of motile sperm and the 1-h migration distance in sodium hyaluronate medium. No correlation between concentration of lymphocytes and presence of antisperm antibodies in seminal plasma was detectable. PMID- 8215698 TI - [Air pollution and cardiovascular disease in Mexico: is there anything to be done?]. PMID- 8215699 TI - [Pulmonary balloon valvulotomy. The results in 42 cases]. AB - The percutaneous balloon valvulotomy is nowadays the treatment of choice for isolated pulmonary stenosis. Forty two patients with congenital pulmonary stenosis underwent balloon valvulotomy at the Instituto Nacional de Cardiologia "Ignacio Chavez". Ages 1 month to 24 years, mean 7.6 +/- 5.9 years, with a follow up of 28.3 +/- 14.8 months. With an infundibular gradient of 50 mm Hg or more a treatment with propranolol was given. After valvulotomy the total basal pressure gradient decrease from 82.9 +/- 40.6 mm Hg to 31.2 +/- 27.1 mm Hg (p < 0.00001). The patient's results were divided in two groups: with and without reactive infundibular obstruction. The 31 patients without infundibular obstruction had a total initial gradient of 71.6 +/- 33.5 mm Hg, and after valvulotomy the gradient was reduced to 18.9 +/- 11.2 mm Hg (p < 0.00001). The 11 patients with infundibular obstruction had a total initial gradient of 114.8 +/- 43.2 mm Hg, and after valvulotomy the valvular gradient was 12.4 +/- 8.5, the infundibular gradient 53.4 +/- 22.9 and the total gradient 65.9 +/- 29.1 mm Hg (p = 0.002 in relation to the basal gradient). All patients with infundibular obstruction (8 treated with Propranolol) and a follow-up of 8.5 +/- 9.8 months underwent Doppler examination, showing a progressive reduction of the total gradient. By six months no one had a total gradient greater than 50 mm Hg. These data confirm that balloon valvulotomy in valvular pulmonary stenosis is safe and effective, and that restenosis is very low. Good results relay on the use of proper balloon diameters (balloon diameter/pulmonary annulus relation of 1.2 to 1.5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215700 TI - [The implantable endocavitary cardioverter-defibrillator: the initial and short term results]. AB - Utilization of endocavitary defibrillation electrodes avoids thoracotomy used in implantable cardioverter-defibrillator procedures, reducing associated morbi mortality. In our institution we have used this approach in 16 patients during a two years period (July 1990-July 1992). Fifteen were males, with a mean age of 56.9 +/- 10.6 (range 32-73). Nine patients suffered ischemic cardiomyopathy, 4 non ischemic cardiomyopathy and in three there was no structural heart disease. Mean ejection fraction was 44.3 +/- 18.3% (range 20-73%). Clinical arrhythmia was ventricular tachycardia in 8 cases, ventricular fibrillation in 6 cases and both types in 2. Endocavitary implantation procedure was not completed in 3 patients, thus an open trans-sternal approach was performed. In 13 patients it was completed successfully, using a total amount of 14 units (1 patient required two procedures due to sepsis in the generator pouch). Most important intraoperative incidences have been defibrillation thresholds between 20-24 J in 4 cases, displacement of defibrillation electrode from vena cava into coronary sinus in 4 cases, epicardial patch implantation via subcostal approach in 1 case and right ventricle perforation in 1 case. No operative mortality was registered. One patient suffered sudden death during follow-up. Surgical complications were few: 1 case of lead dislodgement and 1 infected wound in the generator's pouch. Non surgical complications were also few: 1 case with superior vena cava syndrome and 1 patient with inadequate discharges. In conclusion, due to our early experience, we believe that endocavitary implantation of an implantable cardioverter defibrillator is the procedure of choice at the present time. PMID- 8215701 TI - [Transthoracic and transesophageal echocardiography in the study of young adults with a cerebral ischemic event]. AB - The aim of this study was the evaluation of transesophageal echocardiography (TEE) in the detection of potential emboli sources of cardiac origin in a young population with cerebrovascular events, and to compare this study with transthoracic echocardiography (TE). We have studied 24 young subjects (average 33 years) and detected a potential cardiac source in 9 subjects, with transthoracic approach only in 4. We concluded that TEE is superior than TE to detect potential cardiac source of cerebral embolism. The most frequently abnormality was mitral valve prolapse. PMID- 8215702 TI - [Non-insulin-dependent diabetes mellitus increases early mortality due to acute myocardial infarct]. AB - Previous reports suggest that morbidity and mortality post acute myocardial infarction (AMI) are increased in patients with non-insulin-dependent diabetes (NIDDM). To obtain information in our population related to the prognosis after an AMI in diabetic patients and its major determinants, we studied 96 NIDDM patients admitted consecutively with a diagnosis of AMI. We used a control group (CG) of age and sex matched non-diabetic individuals. Patients with NIDDM had more frequently a history of angina (40 vs 23%, p < 0.001) and previous MI (30 vs 15%, p < 0.05). The AMI localization and extension, and the presence of arrhythmias were similar for both groups. Early mortality after the AMI was 22% in the NIDDM group and 12% in the CG with Odds ratio of 1.9 (CI 95% 0.91-5.15), being higher in diabetic females [2.3 (CI 95% 0.77-14.6) vs female CG and 1.5 (CI 95% 0.8-7.6) vs male NIDDM]. Extended MIs predicted higher mortality rate, especially among NIDDM patients (p < 0.05). Stepwise logistic regression test supported diabetes mellitus, per se, as a major contributor for mortality (p < 0.02), followed by MI localization and extension. The worst outcome was in NIDDM female patients of advanced age and hypertensive (p < 0.00001). PMID- 8215703 TI - [The transatrial-transpulmonary correction of tetralogy of Fallot]. AB - The technical problems and morbi-mortality related with operations in two stages repair of tetralogy of Fallot (T.F) had lead several groups to correct it in early stages. We present 19 infants with T.F operated between July of 1988 and August 1992, 11 males and 8 females whose ages ranged from eleven months to eleven years. Without previous surgery, the preoperative catheterization show 71.4 mm Hg of trans-infundibular gradient. The obstruction was relieved through right atriotomy in combination with one pulmonary arteriotomy from above. The ventricular septal defect was closed. One patient with severe pulmonary hypertension died. The rest show gradient less than 21 mm Hg, and NYHA I-II without medicine (23.1 months of follow up). The echocardiography shows that pulmonary regurgitation was present in 54.9% but only 3 cases was it graded as moderated and none was it severe. Transatrial transpulmonary repairs avoids the depression of ventricular performance caused by transannular corrections with ventriculotomy. Preserves muscular contractions and thus reduces the propensity to right ventricular failure. It can be performed to many patients included anomalous origin of the left anterior descending coronary artery. PMID- 8215704 TI - [The termination of auricular flutter by noninvasive programmed electrical stimulation using a permanent AAI-mode pacemaker]. AB - We describe a case of a 15-year-old boy with an atrial septal defect who three years after the direct closure of the defect presented with atrial flutter type I according to Wells's classification. He was then electrically cardioverted but presented immediately sinus bradycardia and a ventricular escape rhythm that required epicardial pacing (Intermedics 292-03 DASH) in the AAI mode. We report here the successful termination of a new episode of atrial flutter into sinus rhythm with a noninvasive programmed stimulation using his previously implanted pacing system. PMID- 8215705 TI - [Percutaneous mitral commissurotomy with Inoue's technic and pregnancy. The initial experience in Mexico]. AB - From March 1986 to January 1993, we performed percutaneous balloon mitral commissurotomy (PBMC) in ninety-one patients with rheumatic mitral stenosis, two of them during pregnancy. The gestational age at the time of valvotomy was thirty and twenty-seven weeks respectively. Balloon Inoue technique in both cases resulted in improvement in mitral valve area (0.8 vs 1.6 and 0.7 vs 1.9 cm2) and in mean mitral gradient (19 vs 4 and 12 vs 0 mm Hg) immediately after dilation, without residual atrial septal defect or mitral insufficiency. There were no complications. The estimated radiation exposure to the fetus was of 6.4 minutes of fluoroscopy and 6 seconds of angiography. To limit of X-ray irradiation, we used color Doppler echocardiography during dilatation in both cases. The subsequent course of gestation was uncomplicated and normal babies were delivered in both cases. Fetus protection against ionising radiation was assured by lead mantles. In the follow-up the mitral valve area was 1.7 and 2.1 cm2, 15 and 4 months later respectively. PBMC can be performed safely during pregnancy and is effective in increasing the valvular area and relieving symptoms. It offers an excellent alternative for the pregnant patients, with severe mitral stenosis. The risk to the fetus appears lower than previous reports of surgical commissurotomy performed during pregnancy. PMID- 8215706 TI - [Thrombolysis and beta-block in acute myocardial infarct. Their effects on left ventricular function]. AB - The effects of metoprolol or streptokinase or the combination of both drugs on left ventricular function and the rescue of the jeopardized myocardium in patients with acute myocardial infarction (AMI) were compared. Thirty-seven patients with AMI were allocated in 3 different groups: 19 received 15 mg of metoprolol i.v. in 15 minutes, 7 were treated with 1.5 million IU i.v. of streptokinase and 11 more received both drugs. The following variables were studied at control and one and twenty-four hours after treatment; blood pressure, heart rate, "double product", systolic time intervals, diastolic time and the sum of ST-segment elevation and the sum of the R wave in the EKG. Blood pressure, heart rate and "double product" decreased in the groups treated with metoprolol. The pre-ejection time/ejection time index did not change in any group. The diastolic time increased with metoprolol and the sum of ST-segment elevation was more reduced with the combined treatment. Also in this group, the sum of R wave did not decrease as it happened in the other 2 groups. It is concluded that the combination of streptokinase and metoprolol was more effective in the rescue of jeopardized myocardium than metoprolol or streptokinase administered alone. PMID- 8215707 TI - [The immediate results of percutaneous transluminal coronary angioplasty at Hospital San Jose de Monterrey]. AB - We analyzed 69 consecutive PTCA performed upon 64 patients from January 1990 to May 1992. Age was 55 +/- 12 years and 80% were male. Fifty-nine percent were smokers, 32% had hypertension, 16% a remote myocardial infarction, 14% diabetes, 12% previous PTCA, and 6% previous coronary artery bypass surgery. Total cholesterol was 238 +/- 75 mg/dl. Most of the subjects had an acute coronary syndrome, with unstable angina in 31 and a recent myocardial infarction in 23. Angiographically, 52% had single vessel disease, 39% had double vessel and 9% triple vessel disease. LVEF was 55 +/- 11%, LVEDP 17 +/- 10 mm Hg, and 44% had wall motion abnormalities. We dilated 1.4 lesions/patient (1-4), for a total of 100 lesions. Luminal stenosis was reduced from (mean +/- SEM) 88.5 +/- 1.1% to 22.6 +/- 2.2% (p < 0.0001). The procedure was a total clinical success in 85.6% of the patients and a partial clinical success in 4.3%. Complete revascularization was achieved in 62.3% and incomplete but adequate revascularization in 26%. Multiple lesions dilatation was performed in 30% of the patients and multiple vessel angioplasty in 17%. Forty-seven lesions were on the LAD distribution (91.5% angiographic success), 24 on the circumflex (95.8% angiographic success), 26% on RCA (88.4% angiographic success) and 3 in others. There was a 10% failure and 13% complication rates, but more than half of them were successfully managed medically, although 5.7% required urgent CABG. One patient died. PMID- 8215708 TI - [The etiological aspects of heart arrest in pediatrics]. PMID- 8215709 TI - [Cardiac rheumatism. The diagnosis of its evolutionary nature. 1934]. PMID- 8215710 TI - [Remembering Ignacio Chavez on the l4th anniversary of his death. 1989]. PMID- 8215711 TI - Effects of glutathione isopropyl ester on bile flow in glutathione-depleted rats. AB - Combined administration of buthionine sulfoximine (2.5 mmol/kg, i.p.) and diethyl maleate (1.0 ml/kg, i.p.) resulted in a near-complete depletion of hepatic glutathione (0.02 mumol/g liver vs 5.17 mumol/g in saline-treated controls) in male Sprague-Dawley rats. Bile flow was markedly reduced in the rats as compared with the controls and glutathione was not detected in the bile. The linear regression of the correlation between bile flow and endogenous bile-acid excretion rates revealed that no bile acid-independent bile flow was produced in the glutathione-depleted rats. The bile flow was partially restored by an intravenous infusion of glutathione isopropyl ester (1.17 mmol/kg/hr). Glutathione levels were increased in the bile (16 nmol/kg/min) and in the liver (0.55 mumol/g) at the end of the 100 min infusion period of the ester. The increments in bile flow rates were not proportional to the biliary excretion rates of bile acids or glutathione, and the flow rates suddenly increased when glutathione levels in the bile reached an apparent threshold. The increments, not accompanied with an excretion of diethyl maleate-glutathione conjugate, were much greater than expected from the osmotic choleresis of glutathione in the bile. These results indicate that hepatic glutathione above a certain level is required for the formation of a portion of bile flow, and that an intravenous administration of glutathione isopropyl ester is effective in partially restoring the bile formation impaired by glutathione depletion. PMID- 8215713 TI - Antinociception: interaction between adenosine and GABA systems. AB - The interaction of GABA agonists and antagonists with the antinociceptive effects of drugs active on adenosine receptors, was examined in mice using the tail-flick test. Baclofen, but not muscimol (in the doses used), induced antinociception. The adenosine agonist NECA (5'-N-ethylcarboxamidoadenosine) produced a greater degree of antinociception than did PIA (N6-phenylisopropyladenosine). The antinociceptive effect of NECA and PIA was decreased by the GABA antagonists bicuculline, picrotoxin and phaclophen. Combination of theophylline with baclofen, but not with muscimol, induced a high antinociceptive response. Muscimol decreased the antinociceptive effect of NECA, and baclofen increased the antinociceptive action of PIA. It is concluded that there may be an interaction between antinociception induced by GABA and that induced by (an) adenosine mechanism(s). PMID- 8215712 TI - Presence of immunoreactive platelet-activating factor in peritoneal exudate induced by zymosan in rats. AB - The presence of the platelet-activating factor (PAF) in peritoneal exudate, induced by zymosan, was investigated in rats. Intraperitoneal injection of zymosan induced an extravasation of plasma proteins and an accumulation of polymorphonuclear leukocytes in the peritoneal cavity. Zymosan induced a release of immunoreactive PAF in peritoneal exudate which reached maximum levels at 30 min and then declined slowly. Immunoreactive PAF was evenly distributed in the fluid and cellular fractions of the exudate. A PAF-acetyltransferase activity was found as well in the exudate as in plasma. Histamine levels, measured by bioassay, increased after injection of zymosan, reached a peak at 15 min and declined to a normal level within 4 hr. Protein extravasation was inhibited by WEB 2086, a PAF antagonist, during the 6 hours of the study, whereas the accumulation of leukocytes was suppressed at 2 hour by WEB 2086 and SM 12502, two PAF antagonists. PAF is present in the peritoneal exudate induced by zymosan in rats, and plays a role in the development of the inflammatory response. Its main origin might be resident macrophages and polymorphonuclear leukocytes. PMID- 8215714 TI - Potentiation of the antidipsogenic action of alpha-human atrial natriuretic polypeptide at the preoptic area in spontaneously hypertensive rats. AB - The effect of alpha-human atrial natriuretic polypeptides on fluid intake following administration of angiotensin II and 48 hr water deprivation was assessed at the preoptic area in spontaneously hypertensive and normotensive Wistar-Kyoto rats. Angiotensin II (100 ng), injected into the preoptic area, and water deprivation increased the intake of water and of a 2.7% NaCl solution in spontaneously hypertensive as well as in Wistar-Kyoto rats. These intakes were potentiated in the spontaneously hypertensive rats. The fluid intakes evoked by angiotensin II were dose-dependently antagonized by alpha-human atrial natriuretic polypeptide and angiotensin II, administered into the preoptic area, in spontaneously hypertensive but not in Wistar-Kyoto rats. In 48 hr water deprived rats, alpha-human atrial natriuretic polypeptide also inhibited the fluid intake in spontaneously hypertensive but not in Wistar-Kyoto rats. The results suggest that atrial natriuretic polypeptide and angiotensin II may play an important role in controlling fluid intake at the preoptic area level and that these peptides might be involved in the pathogenesis of spontaneously hypertensive rats. PMID- 8215715 TI - Cardiovascular effects of microinjections of thyrotropin-releasing hormone, oxytocin and other neuropeptides into the rostral ventrolateral medulla of the rat. AB - Thyrotropin-releasing hormone, oxytocin, neurotensin, calcitonin gene-related peptide and neuropeptide Y have been proposed as putative neurotransmitters in the rostral ventrolateral medulla of the rat. To investigate the modulation of the basal blood pressure by neuropeptides, we microinjected these neuropeptides into the rostral ventrolateral medulla of the rat and examined their effects on basal blood pressure. Male Wistar rats were anesthetized with urethane, paralyzed and artificially ventilated. Thyrotropin-releasing hormone (0.01-1 ng), oxytocin (1 and 10 ng), neurotensin (0.1-10 ng), calcitonin gene-related peptide (1 and 10 ng) and neuropeptide (1 and 10 ng) produced increases in blood pressure and/or heart rate. Ganglion blockade with hexamethonium (10 mg/kg, i.v.) blocked the pressor responses to thyrotropin-releasing hormone (0.1 ng), oxytocin (10 ng) and neurotensin (10 ng), while methylatropine (1 mg/kg, i.v.) did not affect these responses. Corticotropin-releasing factor (0.1-10 ng) and atrial natriuretic peptide (1 and 10 ng) were ineffective. These findings indicate that many neuropeptides can modify basal blood pressure when injected into the rostral ventrolateral medulla. Whether these neuropeptides play a role in the blood pressure regulation within this brain region remains to be established. PMID- 8215716 TI - Effect of nucleoside transport inhibition on adenosine and hypoxanthine accumulation in the ischemic human myocardium. AB - The effect of nucleoside transport inhibition on the adenylate catabolism was studied in the human myocardium under normothermic ischemic conditions. Ten hearts from cardiac transplant recipients and two hearts from cardiac homograft donors were used in this study. The hearts were excised under hypothermic conditions (25 degrees C body temperature), the coronary arteries flushed with 500 ml ice-cold Ringer solution (n = 6; group I) or with ice-cold Ringer solution containing 1 mg/l of the nucleoside transport inhibitor R75231 (n = 6; group II). After transportation at 0 degree C from the operation room, the hearts were quickly rewarmed to 37 degrees C. Serial transmural biopsy specimens were taken during normothermic ischemia for determination of purine catabolites. The level of ATP before normothermic ischemia was 17.5 +/- 1.0 mumol/g dry weight in the control group (group I) and 19.3 +/- 0.4 mumol/g dry weight in the drug group. ATP, expressed as percentage of total purine content, was similar in both groups before rewarming (79.5 +/- 4.3% in group I and 79.5 +/- 2.9% in group II). There was no significant difference in the rate of ATP breakdown in both groups throughout the experiment (ATP was 3.0 +/- 1.4% of total purines in group I and 1.4 +/- 0.2% in group II at 120 min of normothermic ischemia). Adenine nucleotide content changed also similarly in both groups. Adenosine accumulation was, however, significantly higher in group II than in group I (peak values: 4.6 +/- 1.0% of total purines in group I vs 14.0 +/- 1.7% in group II; p < 0.01). The ratio between adenosine and inosine was significantly higher in group II throughout normothermic ischemia (p < 0.01). In spite of a larger accumulation of adenosine in group II, the increase in inosine was similar in both groups. We conclude that nucleoside transport inhibition significantly delays the breakdown of adenosine and the formation of hypoxanthine in the ischemic human myocardium. PMID- 8215717 TI - Peripherally administered benzodiazepines increase morphine-induced analgesia in the rat. Effect of RO 15-3505 and FG 7142. AB - The influence of alprazolam, chlordiazepoxide and midazolam on the antinociceptive effect of subcutaneous morphine was investigated in rats, using the tail-flick test. After intraperitoneal administration, all drugs significantly enhanced the morphine-induced analgesia. Both the benzodiazepine receptor antagonist RO 15-3505 and the benzodiazepine receptor inverse agonist FG 7142 antagonized the potentiating effect of alprazolam, chlordiazepoxide and midazolam. Our results suggest that the interaction between benzodiazepines and opioids in modulating nociceptive responses involves primarily benzodiazepine receptors and that different pathways are involved in the anxiolytic and pro analgesic actions of benzodiazepines. PMID- 8215718 TI - Oxygen free radicals and protective effect of captopril on myocardial infarct size. AB - Captopril (0.25 mg/kg and 0.5 mg/kg, p.o.) decreased the myocardial infarct size and prevented the progressive decrease in voltage of the R wave in rats. It had no marked effect on systolic blood pressure at these dose levels but higher doses (1 mg/kg, p.o.) reduced systolic blood pressure. It also produced a concentration dependent (50-700 ng/10(6) cells) decrease of chemiluminescence response from rat neutrophils and markedly reduced serum malonyldialdehyde levels, elevated as a consequence of left coronary artery ligation. It is suggested that the protective effect of captopril may be mediated through a decreased formation or scavenging of reactive oxygen species. PMID- 8215719 TI - Effects of gamma-aminobutyric acid on the compound action potential of the rat superior cervical ganglion. AB - The effects on the ganglionic transmission of gamma-aminobutyric acid (GABA) and related drugs were studied in the rat isolated superior cervical ganglion. The extracellularly recorded postganglionic compound action potential was used as an index for ganglionic transmission. GABA reversibly inhibited the ganglionic transmission by blocking the action potential. The effect of GABA is markedly antagonized by bicuculline (20 microM) or picrotoxin (200 microM). Furosemide (1 mM) was also effective in antagonizing the ganglionic effect of GABA. The antagonism by bicuculline was not affected in the presence of pentobarbital (50 microM). Baclofen inhibited the ganglionic transmission through an activation of GABAB receptors since it was markedly antagonized by phaclofen. Muscimol and isoguvacine were less effective than GABA in blocking the ganglionic transmission. The GABA uptake inhibitor isonipecotic acid blocked the ganglionic transmission, probably by activating GABAA receptors, because the effect was antagonized by bicuculline, but the GABA uptake inhibitor guvacine had no significant effect on the ganglionic transmission. These results suggest that GABA causes a ganglionic blockade by activation of both GABAA and GABAB receptor subtypes. PMID- 8215720 TI - The search for prejunctional inhibitory muscarinic receptors in human bronchus. AB - The purpose of our study was to search for and classify prejunctional inhibitory muscarinic receptors in human bronchus with a wide range of muscarinic antagonists. Human bronchial airway smooth muscle strips, collected at thoracotomy from 54 subjects, 31 patients with chronic airway obstruction and 23 control subjects, were suspended in organ baths and stimulated by electrical field stimulation. The stimulation parameters were: frequency: 32 Hz; Grass reading voltage: 70 V (voltage between the electrodes: 15 V); pulse duration: 0.5 msec and train duration: 10 sec, every minute. Twitch responses of smooth muscle strips of 27 subjects (14 with and 13 without chronic airway obstruction) were sufficiently stable to search for the effects of M1-, M2- and M3-selective antagonists. All antagonists were added to the bath in a cumulative manner and decreased twitch contraction. No convincing evidence was found for the presence of prejunctional inhibitory muscarinic receptors of the M2-subtype, reasons for this obvious absence are discussed. Anaesthetical drugs for example, may mask the prejunctional inhibitory muscarinic receptors. The question remains whether the used electrical field stimulation experiments are suitable to point out prejunctional inhibitory muscarinic receptors. It is concluded that additional experiments with other experimental methods and in patients with different anaesthetical treatment are needed. PMID- 8215721 TI - Loosening criteria for withholding prehospital cardiopulmonary resuscitation. Futility of prehospital cardiopulmonary resuscitation: like beauty, in the eyes of the beholder. PMID- 8215722 TI - An ethical analysis of the use of 'futility' in the 1992 American Heart Association Guidelines for cardiopulmonary resuscitation and emergency cardiac care. PMID- 8215723 TI - The impact of female hormone usage on the lipid profile. The Framingham Offspring Study. AB - BACKGROUND: Exogenous female hormone use appears to affect cardiovascular disease risk in both premenopausal and postmenopausal women. The purpose of this study was to evaluate the impact of exogenous female hormone usage on the lipid profile among premenopausal and postmenopausal women. METHODS: One thousand nine hundred thirty female participants of the Framingham Offspring study comprised the study population. Of the 992 premenopausal subjects, 57 were current oral contraceptive users; among the 938 postmenopausal subjects, 80 were current hormone users. The influence of hormone use on lipid and lipoprotein levels was determined using multivariable linear regression models that adjusted for age, body mass index, smoking, alcohol intake, beta-blocker, and diuretic therapy. Adjusted least squares means were calculated for each lipid and lipoprotein according to female hormone usage and menopausal status. RESULTS: In the premenopausal analysis, pooled oral contraceptive use was significantly related to increased levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol and apolipoprotein A-I. Increased estrogen content was inversely associated with low density lipoprotein cholesterol, and apolipoprotein B levels, while increased progestin content was inversely related to high-density lipoprotein cholesterol and apolipoprotein A-I levels. Among postmenopausal women, use of premarin only was significantly associated with increased high-density lipoprotein cholesterol and apolipoprotein A-I levels. Combination use of premarin and provera was significantly associated with increased apolipoprotein A-I levels; less powerful but still significant associations with increased high-density lipoprotein cholesterol and decreased low-density lipoprotein cholesterol were also observed. CONCLUSION: In this cross-sectional analysis, oral contraceptive use is associated with both favorable and unfavorable lipid alterations with respect to atherogenic risk. Among postmenopausal women, hormone replacement therapy (both premarin only and combined premarin and provera) appears to be associated with favorable effects on the lipid profile. PMID- 8215724 TI - Plasma lipoprotein levels as predictors of cardiovascular death in women. AB - BACKGROUND: The association of lipoprotein levels with cardiovascular disease (CVD) is less well understood in women than in men. To better characterize any relationships, associations between CVD death and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol and triglyceride levels in women were explored using data from female participants in the Lipid Research Clinics' Follow-up Study. METHODS: Using a sample of 1405 women aged 50 to 69 years from the Lipid Research Clinics' Follow-up Study, age-adjusted CVD death rates and summary relative risk (RR) estimates by categories of lipid and lipoprotein levels were calculated. Multivariate analysis was performed to provide RR estimates adjusted for other CVD risk factors. RESULTS: Average follow up was 14 years. High-density lipoprotein and triglyceride levels were strong predictors of CVD death in age-adjusted and multivariate analyses. Low-density lipoprotein and total cholesterol levels were poorer predictors of CVD mortality. After adjustment for other CVD risk factors, HDL levels less than 1.30 mmol/L (50 mg/dL) were strongly associated with cardiovascular mortality (RR = 1.74; 95% confidence interval [CI], 1.10 to 2.75). Triglyceride levels were associated with increased CVD mortality at levels of 2.25 to 4.49 mmol/L (200 to 399 mg/dL) (RR = 1.65; 95% CI, 0.99 to 2.77) and 4.50 mmol/L (400 mg/dL) or greater (RR = 3.44; 95% CI, 1.65 to 7.20). At total cholesterol levels of 5.20 mmol/L (200 mg/dL) or greater and at all levels of LDL and triglycerides, women with HDL levels of less than 1.30 mmol/L (< 50 mg/dL) had CVD death rates that were higher than those of women with HDL levels of 1.30 mmol/L (50 mg/dL) or greater. CONCLUSIONS: High density lipoprotein and triglyceride levels are independent lipid predictors of CVD death in women. Cholesterol screening guidelines should be re-evaluated to reflect the importance of HDL and triglyceride levels in determining CVD risk in women. PMID- 8215725 TI - Prophylactic agents for venous thrombosis in elective hip surgery. Meta-analysis of studies using venographic assessment. AB - BACKGROUND: We determined the relative efficacy of various agents or combinations of agents in the prophylaxis of deep venous thrombosis after elective hip arthroplasty. METHODS: Peer-reviewed, English-language, human studies articles from 1975 through 1991 were obtained through a MEDLINE database search. Additional references were obtained from bibliographies. Articles that compared the effect of two or more prophylactic agents or placebo in preventing deep venous thrombosis as assessed by venography were selected for further review. Only studies of elective hip surgery in which all patients had venographic screening for thrombosis were included. Twenty-three of 101 studies met these criteria. Data were abstracted by one of us. Methodologic criteria and outcome data from each study were recorded and analyzed. RESULTS: There was significant heterogeneity in the deep venous thrombosis rate among studies. Although the rates were lowest for low-molecular-weight heparin with or without the use of stockings, adjusted-dose heparin, and warfarin, many agents had similar low rates. There was less heterogeneity when the relative risk was used as a summary statistic for studies in which two agents were compared. With pairwise comparisons, low-molecular-weight heparin performed better than every agent with which it was compared. Other agents performed well but were not consistently better. CONCLUSIONS: Multiple agents or combinations are effective prophylaxis for deep venous thrombosis, but none decreases the rate to zero. There was overlap in the 95% confidence intervals for the probability of deep venous thrombosis for various agents and especially for the probabilities for proximal thrombi. Many agents have not been compared directly with each other, but low molecular-weight heparin consistently performed well. PMID- 8215726 TI - Progression of functional disability in patients with rheumatoid arthritis. Associations with rheumatology subspecialty care. AB - BACKGROUND: To determine whether patients with rheumatoid arthritis and their physicians make appropriate decisions regarding referral to rheumatologists and the need for continuing rheumatology care, we examined the relationship between the progression of functional disability in these patients and their use of rheumatology subspecialty care over time. METHODS: A cohort of 282 patients with rheumatoid arthritis was followed prospectively for up to 10 years. Participants were categorized into three subgroups based on the pattern of care received from rheumatologists over the study period: patients who were never treated by a rheumatologist; patients treated by a rheumatologist only intermittently; and patients treated by a rheumatologist at least once during each 6-month study period. The outcome was the rate of progression of functional disability, measured using the Health Assessment Questionnaire Disability Index. RESULTS: Among the 52 patients who had not been referred to a rheumatologist, 30 (58%) had rates of progression of functional disability that were stable or improving over time (rate < 0.01 Disability Index units per year), while 22 (42%) had rates that were worsening (rate > or = 0.01 Disability Index units per year). Among patients treated by rheumatologists, the average rate of progression was substantially lower among the 69 patients who were treated regularly by a rheumatologist than among 161 patients treated by rheumatologists intermittently (0.008 Disability Index units per year vs 0.020 Disability Index units per year). This difference was associated with more intensive use of second-line antirheumatic medications, and more frequent joint surgeries, among patients treated by rheumatologists on a regular basis. CONCLUSIONS: Most patients with rheumatoid arthritis in this community cohort were treated by a rheumatologist, but 42% of those not referred had progressively increasing functional disability. Among patients treated by rheumatologists, those who had continuing care from rheumatologists experienced lower rates of progression of functional disability than those who had only intermittent care. These results suggest that use of rheumatology subspecialty care is associated with better health outcomes in rheumatoid arthritis. PMID- 8215727 TI - The sepsis syndrome in a Dutch university hospital. Clinical observations. AB - BACKGROUND: Most studies of the cause of sepsis syndrome focus on patients hospitalized in intensive care units. In this study, we analyzed the incidence, cause, and outcome of the sepsis syndrome in all hospitalized patients. METHODS: Clinical and microbiologic data were obtained for 382 patients (5.6% of all patients admitted) from whom blood was drawn for culture. RESULTS: The incidence of the sepsis syndrome was 13.6 per 1000 patients admitted (1.06 per 1000 hospital days), while the incidence of septic shock was 4.6 per 1000. The respiratory tract was the predominant infection site. Of all patients with sepsis syndrome, 38% (n = 35) had positive blood cultures. More than half of these cultures (13 [57%]) were caused by gram-positive microorganisms (excluding patients receiving selective decontamination of the digestive tract and those with intravascular device-related bacteremias). The mortality for patients with sepsis syndrome without shock was 28% (17/61), while for patients with septic shock, it was 55% (17/31). Patients with cardiovascular diseases had a significantly (P < .005) greater risk of dying during a sepsis syndrome episode than patients with other predisposing factors. Multivariate analysis of factors influencing outcome identified the development of shock and an immunocompromised state as being significantly associated with outcome in patients with sepsis syndrome. CONCLUSIONS: Patients fulfilling the criteria for the sepsis syndrome are at great risk of developing septic shock or multiple-organ failure and subsequently dying. In our hospital, the majority of bacteremic episodes were associated with gram-positive microorganisms. PMID- 8215728 TI - A randomized trial of nortriptyline for severe chronic tinnitus. Effects on depression, disability, and tinnitus symptoms. AB - OBJECTIVE: To determine whether the antidepressant, nortriptyline, is effective for treatment of depression, tinnitus-related disability, and tinnitus symptoms in patients with severe chronic tinnitus. DESIGN: A 12-week, double-blind, randomized controlled trial. SETTING: A university otolaryngology clinic. PATIENTS: Ninety-two subjects with severe chronic tinnitus: 38 with current major depression and 54 with depressive symptoms and significant tinnitus-related disability. INTERVENTION: Nortriptyline (maintained at 50 to 150 mg/mL for 6 weeks) or placebo. MAIN OUTCOME MEASURES: Hamilton Depression Rating Scale, Tinnitus Disability Measures, and Audiometric Measures. RESULTS: Nortriptyline was superior to placebo by multivariate analysis of covariance for depression (10.6 vs 14.3 final Hamilton Depression score), for tinnitus-related disability (1.8 vs 2.4 final MPI Tinnitus Interference), and tinnitus loudness (13.6 vs 20.0 dB final loudness match [in worst ear at tinnitus frequency]). When major depression and depressive symptoms groups were considered separately, nortriptyline was superior to placebo on these same measures but differences did not achieve statistical significance. CONCLUSIONS: The antidepressant nortriptyline decreases depression, functional disability, and tinnitus loudness associated with severe chronic tinnitus. What appears to be irreversible disability of otologic origin may, in part, be reversible disability of psychiatric origin. PMID- 8215729 TI - Significance of isolated hepatitis B core antibody in blood donors. AB - BACKGROUND: About 25% of blood donors who test positive for antibody to hepatitis B core antigen (anti-HBc) have no other positive hepatitis B serologic results. Because of the potential importance and diagnostic uncertainty of this test result, we studied its significance by assessing the serologic response to hepatitis B vaccine in donors with an isolated anti-HBc pattern. METHODS: Specimens from 300 blood donors that were positive for anti-HBc by enzyme immunoassay were tested for anti-HBc by radioimmunoassay and for antibody to hepatitis B surface antigen (anti-HBs). A subgroup of 37 were further studied after administration of hepatitis B vaccine and compared with 34 similarly vaccinated age- and sex-matched seronegative controls. Measurements of anti-HBs were made at vaccination and 1, 2, 4, 8, 25, and 30 weeks after initial vaccination. RESULTS: Among 300 donors who tested positive for anti-HBc by enzyme immunoassay, the radioimmunoassay for anti-HBc was negative in 76 (25.3%) and the test for anti-HBs was negative in 104 (34.7%). Significant differences were observed for radioimmunoassay anti-HBc and anti-HBs titers, alanine aminotransferase, and male-female ratios between four distinct serogroups (A through D) defined by the combination (positive/negative) of radioimmunoassay anti-HBc and anti-HBs results. No significant differences between the study and control groups were observed in the magnitude of anti-HBs responses at any of the six postvaccine testing periods. CONCLUSIONS: Isolated anti-HBc in US blood donors is usually a false-positive result, regardless of the titer. PMID- 8215730 TI - Chronic rubella vaccine-associated arthropathy. AB - Rubella immunization or infection is an uncommonly recognized cause of acute, recurrent, or persistent musculoskeletal manifestations. After routine rubella immunization, two women presented with the onset of polyarthralgia, arthritis, maculopapular rash, fever, paresthesia, and malaise with persistent or recurrent manifestations lasting longer than 24 months after vaccination. The patients expressed rubella virus RNA in peripheral-blood leukocytes 10 and 8 months after vaccination, respectively, in contrast to repeated negative results in asymptomatic rubella-immunized controls. One patient developed significantly depressed antibody responses to rubella virus after vaccination and experienced a prolonged clinical improvement after a 3-month course of intravenous immune globulin. The second patient had normal antibody responses to rubella virus and underwent no clinical improvement during or after intravenous immune globulin therapy. Rubella immunization or infection should be considered as additional causative factors in evaluation of acute and continuing musculoskeletal syndromes. PMID- 8215731 TI - Sequential staging systems for small-cell lung cancer. PMID- 8215732 TI - Priapism in sickle cell disease: possible contributory effect of cocaine use. PMID- 8215733 TI - Structure and function of academic divisions of cardiology. Task Force Reports from the Association of Professors of Cardiology. AB - The discipline of cardiovascular medicine has undergone a striking transformation in recent decades. The field has always been of primary importance in medicine, because of the high prevalence of diseases of the cardiovascular system. However, progress in the treatment of patients with cardiovascular disease has been substantial, and overall mortality from this cause has declined significantly. Nevertheless, cardiovascular disease remains the most frequent cause of death in this country and is also an important cause of morbidity. PMID- 8215734 TI - Predicting the course of peritonitis in patients receiving continuous ambulatory peritoneal dialysis. AB - BACKGROUND: Peritonitis is a common problem for patients receiving continuous ambulatory peritoneal dialysis. Episodes that do not respond to antibiotics within 96 hours are associated with substantial morbidity and mortality. The purpose of this study was to develop a method for identifying these patients at the time of hospital admission. METHODS: We reviewed all cases of peritonitis associated with continuous ambulatory peritoneal dialysis that occurred at the Albuquerque (NM) Veterans Affairs Medical Center during a 10-year period. Episodes of peritonitis were randomly assigned to a training set or a validation set. Persistent infections were those lasting more than 96 hours. For training cases, stepwise logistic regression was used to develop a predictive model for persistent infection using information available at the time of hospital admission. The model was then used to assign validation cases to "high-" and "low risk" categories. The group difference in the proportion of persistent cases was tested by chi 2 analysis. RESULTS: Sixty patients had 120 episodes of peritonitis during the study period. Of 63 episodes assigned to the training set, 26 (41.3%) lasted more than 96 hours (persistent cases) and 37 were cured in 96 hours or less (usual cases). Compared with usual cases, persistent episodes were characterized by a higher age at presentation and a greater decline from preinfection values for hemoglobin and serum potassium, serum urea nitrogen, creatinine, albumin, and calcium. Advanced age and marked declines in serum potassium and albumin levels were identified by logistic regression as independent risk factors for persistent infection. The model identified 28 of 57 validation cases as high risk. Compared with low-risk cases, these episodes were much more likely to be persistent (64.3% vs 24.1%; P = .002) and result in death (32.1% vs 3.4%; P = .005). CONCLUSIONS: Advanced age and marked declines in serum albumin and potassium levels are poor prognostic signs in peritonitis associated with continuous ambulatory peritoneal dialysis. Patients with these findings should be treated aggressively. PMID- 8215735 TI - Prevalence of silent myocardial ischemia and arrhythmias in patients with coronary heart disease undergoing gastrointestinal tract endoscopic procedures. AB - BACKGROUND: Since the introduction of gastrointestinal tract endoscopic procedures, there has been concern about cardiovascular complications, especially in patients with coronary heart disease. Although, in general, these procedures are safe, previous studies have documented perturbations in blood pressure, heart documented perturbations in blood pressure, heart rate, and oxygen saturation, as well as the occurrence of arrhythmias and nonspecific ST-segment electrocardiographic changes during such procedures. No studies, however, have specifically addressed the prevalence of silent myocardial ischemia and arrhythmias in patients with well-established coronary heart disease. METHODS: During a 15-month period, 25 hospitalized patients with well-defined coronary heart disease underwent continuous ambulatory electrocardiographic recording during endoscopic procedures requiring intravenous sedation, as well as during a prolonged baseline period. All patients were considered clinically stable, although 92% were categorized as being at intermediate or high coronary risk by standard risk stratification criteria. Eleven patients (44%) had had previous myocardial infarction, and 68% reported a history of angina. RESULTS: Although 24% of patients had one or more episodes of electrocardiographic ischemia during the recording periods, no patient had evidence of ischemia exclusively during the endoscopic procedure. Arrhythmias were no more frequent during the endoscopic procedures than during a corresponding baseline period. Symptomatic angina or serious arrhythmias did not occur during the procedures. CONCLUSIONS: Our data suggest that endoscopic procedures in patients with stable but severe coronary heart disease, when performed with standard medications, monitoring, and techniques, rarely result in silent or symptomatic myocardial ischemia or serious arrhythmias. In addition, although asymptomatic minor arrhythmias are common during endoscopic procedures, their occurrence appears less frequent than during daily hospital life. PMID- 8215736 TI - Addressing the public's concerns about human immunodeficiency virus transmission in health-care settings. AB - BACKGROUND: The 1990 report of a cluster of patients infected with the human immunodeficiency virus (HIV) associated with a Florida dentist with acquired immunodeficiency syndrome attracted considerable media coverage and legislative attention. A number of polls found that the public favored mandatory HIV-antibody testing of health-care workers. The Centers for Disease Control and Prevention, Atlanta, Ga, conducted a two-phase study to understand how public concerns regarding potential HIV transmission in health-care settings can be addressed by the medical and public health communities. METHODS: Sixteen focus group discussions in nine US cities were conducted to explore the public's perceptions, concerns, and behavioral responses regarding HIV transmission in health-care settings. Using this information, a questionnaire was developed and administered to a nationwide probability telephone sample of 1150 adults. RESULTS: Concern about contracting HIV in health-care settings was highest for emergency department treatment and lowest for treatment by a personal physician. Two factors directly related to patient care, ie, the health-care professional's willingness to discuss acquired immunodeficiency syndrome and the presence of acquired immunodeficiency syndrome educational materials in the waiting room, were considered useful factors for determining potential risk of transmission of HIV in a health-care setting. CONCLUSIONS: Public concern about the potential for HIV transmission in health-care settings remains high. Active steps on the part of health-care professionals, such as providing educational materials and initiating discussions about infection control procedures and about HIV and acquired immunodeficiency syndrome, could likely have positive effects in terms of alleviating these concerns. PMID- 8215737 TI - Recruitment of primary care physicians to care for patients with human immunodeficiency virus infection in a large northwestern county. AB - BACKGROUND: We evaluated an initiative to recruit and to educate physicians to care for persons with human immunodeficiency virus (HIV) infection in King County, Washington, and to refer patients to them through a centralized telephone referral service (the acquired immunodeficiency syndrome [AIDS]/HIV Care Access Project). METHODS: Six physicians trained in AIDS care recruited primary care physicians in clinics throughout King County; the physician cohort was monitored for behavior in accepting referrals during the ensuing year. RESULTS: Of 250 primary care physicians contacted initially, 79 of 120 who met with AIDS-trained physicians were willing to accept patient referrals. Willingness was not related significantly to age, sex, years in practice, or specialty, but was related to level of experience with HIV/AIDS care and current practice. The recruitment initiative increased the physicians available to the telephone referral service by 93% (from 85 to 164). More physicians (41) joined the referral service in the ensuing year, during which 647 patient referrals were made to these 205 physicians (median referral rate of one patient per quarter). Four physicians requested cessation of referrals, however, two later asked for referrals to continue. CONCLUSION: The recruitment initiative was successful in increasing the number of primary care physicians available to accept patients with HIV infection into their practices (thereby reducing the burden of HIV referrals on a small pool of providers), and in establishing a county-wide telephone service to coordinate these referrals. The initiative was self-sustaining, with an ongoing influx of new providers willing to take referrals. PMID- 8215738 TI - Familial defective apolipoprotein B-100 is clinically indistinguishable from familial hypercholesterolemia. AB - BACKGROUND: Familial defective apolipoprotein B-100 is caused by a substitution of adenine for guanine in exon 26 of the gene coding for apolipoprotein B, which results in the substitution of glutamine for arginine in the putative low-density lipoprotein-receptor binding domain of the mature protein. This amino acid substitution diminishes the binding capacity of the low-density lipoprotein particle for the low-density lipoprotein receptor, which in turn leads to an increase in levels of plasma total and low-density lipoprotein cholesterol. METHODS: To identify carriers of this mutation by means of molecular biology techniques in a large cohort of Dutch patients living in the Netherlands and in Canada with primary hypercholesterolemia, to establish the frequency of the disorder, and to investigate its clinical signs and symptoms and the response to cholesterol-lowering therapy. RESULTS: A total of 1248 patients were screened, and the mutation was found in 18 patients who were initially all diagnosed as having familial hypercholesterolemia. Ten of 18 patients had tendon xanthomas or an arcus cornealis or both, and eight of 18 patients had angina or other evidence of coronary artery disease. CONCLUSIONS: The disorder was clinically indistinguishable from familial hypercholesterolemia in terms of physical characteristics and lipoprotein measures. Response to lipid-lowering therapy with beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors was similar to that reported in patients with familial hypercholesterolemia. The mutation was associated with a similar haplotype, which was also reported in other patients of Western European descent with familial defective apolipoprotein B100. This strongly suggests that the mutation has a common chromosomal background that originated in Western Europe. PMID- 8215739 TI - A review of the clinical effectiveness of exercise therapy for intermittent claudication. AB - BACKGROUND: Intermittent claudication is both frequent and disabling. Conservative treatment consists of the elimination of risk factors, particularly smoking, drug treatment, and physical exercises. This review represents an attempt to define how effectively exercise prolongs the walking ability of claudicants. METHODS: A computerized literature search was done to identify all controlled trials on the subject. In addition, other studies were admitted if they were in accordance with certain quality criteria. RESULTS: Without exception, these studies showed that exercise can prolong the pain-free walking distance of claudicants. Even though this message seems uniform and convincing, one should point out that all trials are burdened with methodological flaws. The variability of increase in walking ability demonstrated in these studies is impressive and cannot be fully explained. A multitude of possible mechanisms could be involved in bringing about the clinical effect; at present it is impossible to define their relative importance. CONCLUSIONS: The optimal exercise program should be supervised, performed regularly for at least 2 months, and of high intensity. Appropriate steps to guarantee patients' compliance must be taken. Even though many fundamental questions remain unanswered, it is justified to prescribe exercise therapy for intermittent claudication more generally than is realized in today's practice. PMID- 8215741 TI - Reduced severity of eosinophilia-myalgia syndrome associated with the consumption of vitamin-containing supplements before illness. AB - OBJECTIVE: To determine if the severity of subacute symptoms in eosinophilia myalgia syndrome (EMS) was affected by medical history or use of nutritional supplements other than tryptophan before illness. DESIGN AND STUDY POPULATION: A case-control study was conducted of EMS cases systematically sampled from all those reported to a statewide surveillance system in California in 1989. Excluding two previous EMS-related deaths, interviews were completed in 73% (57/78) of the eligible case patients sampled. MAIN OUTCOME MEASURES: The severity of any myalgia(s), dyspnea, or walking impairment during each of the first 3 months of EMS was quantified by means of self-reported integer scores ranging from 0 (asymptomatic) to 10 (severe symptoms). Case patients in the top tercile of combined, unweighted monthly scores were defined as having severe symptoms. RESULTS: All interviewees (57 of 57) had consumed supplemental tryptophan before illness; 89% (51/57) were female. The odds of severe symptoms were not significantly associated with gender, age, previous antidepressant use, or cumulative amounts of supplemental tryptophan consumed before or after EMS onset (P > .1). Previous consumption of any multivitamin(s), however, was associated with significantly lower odds of severe symptoms (adjusted odds ratio, 0.05; 95% confidence limits, 0.007, 0.4; P = .006). CONCLUSIONS: The consumption of multivitamin-containing supplements before EMS appears to have modified the severity of subacute symptoms in this sample of cases from California. PMID- 8215740 TI - Serum complements. Inappropriate use in patients with suspected rheumatic disease. AB - BACKGROUND: The diagnostic value of serum complement testing is well established in inherited complement deficiencies and glomerulonephritis. Their utility is less certain in diagnosing rheumatic diseases. We noted that complement tests were frequently ordered for patients who were referred to our rheumatology clinic. We sought to determine the clinical rationale for ordering complement tests in our hospital and the effect of the test results in patients with rheumatic diseases. METHODS: We conducted a retrospective medical chart review of patients who had serum complement tests ordered at our hospital. We determined whether the test was ordered as a diagnostic tool in a patient with a suspected rheumatic disease. In these cases, we attempted to correlate the results of the complement tests with the patient's eventual diagnosis. RESULTS: We obtained the medical charts of 130 patients who had 307 complement assays (C3, C4, or total hemolytic complement) performed between October 1988 and July 1989. The tests were ordered for diagnostic reasons in 68% of the patients; 54% of these were ordered by nonspecialists. The complement tests were ordered on 28 patients with suspected rheumatic diseases. The three patients with hypocomplementemia did not have a connective tissue disease. The 10 patients who eventually were diagnosed as having rheumatic disease all had normal serum complement levels. Additionally, we found that 77% of patients had more than one complement assay ordered. The test results were discordant in only 24% of these cases. CONCLUSION: Complement screening is not a useful diagnostic test in most patients with suspected rheumatic disease. Despite their lack of established diagnostic value, these tests were frequently performed in our hospital. Judicious use of complement testing would provide substantial cost savings without a loss of clinically relevant information. When the complement testing is clinically indicated, clinicians should consider using a single C3 assay initially rather than multiple assays unless a hereditary deficiency is suspected. PMID- 8215742 TI - Increased osmolal gap in alcoholic acidosis. AB - We studied a patient with alcoholic acidosis and an increased osmolal gap. Ethyl alcohol and other compounds that are known to increase serum osmolality in alcoholics were not detected. However, the levels of glycerol, acetone, and the acetone metabolites acetol and 1,2-propanediol were increased in the serum of this patient. On admission and 3 and 7 hours after admission, the combined serum osmolality of glycerol, acetone, acetol, and 1,2-propanediol accounted for 48%, 92%, and 62% of the increase in the osmolal gap above the highest normal level of 10 mOsm/kg H2O. The disappearance of the osmolal gap correlated with the correction of the acidosis and the concomitant reduction in serum glycerol and acetone levels. Elevations of endogenous glycerol, acetone, and acetone metabolite levels should now be added as causes for an increased osmolal gap in the alcoholic patient. Ingestion of toxic alcohols can no longer be assumed to be the only cause for an increased osmolal gap in alcoholic patients. PMID- 8215743 TI - Enterobacter agglomerans--associated cotton fever. AB - Cotton fever is usually a benign febrile, leukocytic syndrome of unknown etiology seen in intravenous narcotic abusers. Cotton and cotton plants are heavily colonized with Enterobacter agglomerans. We report a case of cotton fever associated with E agglomerans in which the organism was first isolated from the patient's blood and secondarily from cotton that he had used to filter heroin. Enterobacter agglomerans is with most probability the causal agent of cotton fever. Patients presenting with the classic history should have blood cultures performed and should be started on a regimen of empiric antibiotic therapy. PMID- 8215744 TI - Pharmacists are health care providers too. PMID- 8215745 TI - Can the nebulizer survive? PMID- 8215746 TI - Nonsteroidal anti-inflammatory drugs, ulcers, and histamine2 blockers. The ostrich phenomenon! PMID- 8215747 TI - Angiotensin-converting enzyme inhibition and renal protection. An assessment of implications for therapy. AB - The role of hypertension in the pathogenesis of renal damage is a subject of both historical interest and current investigation. Because of the difficulty associated with studying the pathophysiologic role of glomerular injury in systemic hypertension, experimental models have provided much of the data in this field. The mechanisms leading to glomerular injury are complex and not fully elucidated. Mesangial and endothelial cell injury are thought to be important pathophysiologic mechanisms in the renal injury associated with hypertension. One hypothesis suggests that glomerular hypertension (ie, a hemodynamic event) is the primary pathogenetic mechanism, but another supports the notion that glomerular hypertrophy (ie, abnormal growth-related events) contributes to injury. The intrarenal renin-angiotensin system may play an important pathogenetic role in end-stage renal disease. Angiotensin-converting enzyme (ACE) inhibition has been shown to arrest the progression of renal injury in animal models. Although the clinical database is incomplete, the findings of anecdotal reports and short-term studies suggest that ACE inhibition may preserve renal function in patients with scleroderma renal crisis, reduce proteinuria in patients with diabetic nephropathy, and normalize renal hemodynamics in patients with a variety of renal diseases. The beneficial effects of ACE inhibition may be due to both hemodynamic (eg, reduction in glomerular capillary and intraglomerular pressures) and nonhemodynamic (eg, potassium-sparing and reduction in mesangial proliferation) mechanisms. The precise role of ACE inhibitors in the prevention of renal damage awaits the results of ongoing long-term, double-blind clinical studies. Nevertheless, ACE inhibition may be an appropriate therapeutic alternative in the hypertensive patient whose renal injury is progressing despite aggressive antihypertensive therapy. PMID- 8215748 TI - Occupational infection in health care. The century-old lessons from syphilis. AB - The dangers of occupational infection (where the infectious agent was acquired during the provision or receipt of a medical service) have received renewed interest in the era of the human immunodeficiency virus. The dilemmas raised by this phenomenon, however, are far from novel and were the subject of considerable debate in the medical literature at the turn of the century with regard to syphilis. After recognition of the problem, it took time to manage syphilis effectively through technical innovation, personal prophylaxis, education, and regulation. These efforts led to the development of a strategy remarkably similar to that of the "universal precautions" approach applied to human immunodeficiency virus today. PMID- 8215749 TI - Nizatidine prevents peptic ulceration in high-risk patients taking nonsteroidal anti-inflammatory drugs. AB - BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) use is increasingly recognized as a major factor associated with peptic ulcer disease and complications. We undertook a multicenter, double-blind, placebo-controlled trial to evaluate efficacy and safety of nizatidine in preventing ulcer formation in patients with osteoarthritis who were taking NSAIDs. METHODS: After endoscopy to rule out the presence of an acute ulcer, 496 patients were randomized to receive nizatidine, 150 mg twice daily (248 patients) or placebo (248 patients) for 3 months. Repeated endoscopies were performed monthly. We defined failure as development of a peptic ulcer (> or = 0.3 cm in diameter). RESULTS: Baseline characteristics tested were comparable for the two groups with regard to age, sex, ulcer history, and Helicobacter pylori status. Overall ulcer occurrence in the nizatidine group (9.7%) was not significantly different from that in the placebo group (13.7%; P = .163). High-risk subgroups (patients with ulcer history and patients > or = 65 years of age), however, revealed statistically fewer ulcers for patients receiving nizatidine (P = .035 and P = .042, respectively). Analysis of antacid use showed significantly less use in nizatidine recipients, although there were similar percentages of patients showing improvement in dyspeptic symptoms in each treatment group. We failed to observe a conclusive correlation between H pylori status at baseline, as measured by serum immunoglobulin antibody, and development of an ulcer. CONCLUSIONS: This study showed that nizatidine, 150 mg, twice daily, significantly reduces the incidence of ulcer formation in high-risk patients taking long-term NSAID therapy. It also relieves NSAID-associated dyspeptic symptoms in some patients. PMID- 8215750 TI - The impact of cigarette and alcohol consumption on weight and obesity. An analysis of 1911 monozygotic male twin pairs. AB - BACKGROUND: The objective of this investigation was to examine the relationships among cigarette and alcohol consumption and weight and obesity. Although previous research demonstrated that smoking is associated with reduced weight, data on the relationship between alcohol consumption and weight are conflicting. In addition, the influence of smoking cessation on the risk of obesity at a level that adversely affects health has not been fully examined. METHODS: By means of a cotwin-control research design, cigarette and alcohol consumption and weight measurements derived from 1911 male, monozygotic twins were compared with those of their identical siblings. This approach eliminates confounding from a large number of measurable and unmeasurable environmental experiences and the well documented influence of inherited factors on weight and cigarette and alcohol consumption. RESULTS: After adjustment for a variety of socioeconomic factors, light (one to 19 cigarettes daily), moderate (20 to 29 cigarettes daily), and heavy (> 29 cigarettes daily) smokers were an average of 3.2, 2.4, and 4.0 kg lighter, respectively, than nonsmokers. Past smokers demonstrated a 33% higher prevalence of clinically significant obesity (body mass index > 27.8 kg/m2) by comparison with their currently smoking siblings (26.5% vs 19.9%, respectively; difference, P < .001) and a 1.8 times increased risk (95% confidence interval, 1.1 to 2.9) of clinically significant obesity by comparison with heavy smokers. By contrast, alcohol consumption had no significant influence on weight or obesity. CONCLUSIONS: Smoking cessation efforts provided by health practitioners to men should consider routinely offering a weight management component to reduce weight gain and further improve the well-documented health benefits of not smoking. It may not be necessary for alcohol treatment programs to adopt a similar policy. PMID- 8215751 TI - A reevaluation of aspirin therapy in rheumatoid arthritis. AB - BACKGROUND: Aspirin therapy has been largely superseded by prescription nonsteroidal anti-inflammatory drug (NSAID) therapy in rheumatoid arthritis, in part because of premarketing studies suggesting lesser toxic effects for NSAIDs than for aspirin. This study evaluates these toxic effects in a postmarketing population of patients with rheumatoid arthritis. METHODS: We studied 1521 consecutive courses of aspirin and 4860 courses of NSAIDs in patients with rheumatoid arthritis from eight Arthritis, Rheumatism, and Aging Medical Information System Post-marketing Surveillance Centers. Toxicity index scores were generated from symptoms, laboratory abnormalities, and hospitalizations, weighted for variable severity and severity of side effect. RESULTS: The toxicity index was only 1.37 (SE = 0.10) for aspirin and 1.87 to 2.90 for selected nonsalicylate NSAIDs. These differences were consistent across centers and remained after statistical adjustment for differing patient characteristics. There was a different toxicity with different aspirin preparations, with a score for plain aspirin of 1.36 (SE = 0.23), for buffered aspirin of 1.10 (0.20), and for enteric-coated aspirin preparations of 0.92 (0.14). Most important, there were strong dose effects, with a score of 0.73 (0.09) for 651 to 2600 mg daily, 1.08 (0.17) for 2601 to 3900 mg, and 1.91 (0.38) for more than 3900 mg. The average aspirin dose taken was only 2665 mg/d, approximately eight "tablets," compared with 3600 to 4800 mg/d used in the 16 pivotal premarketing studies reviewed. Average NSAID doses were, on the other hand, lower in premarketing trials (eg, naproxen 500 mg/d vs 773 mg/d in the Arthritis, Rheumatism, and Aging Medical System clinical practices). CONCLUSIONS: Aspirin therapy, in doses commonly employed in practice, has an excellent safety profile in rheumatoid arthritis, and it is the least costly NSAID. The safety advantage is explained primarily by a dose effect and secondarily by possible differences between formulations. Newer management strategies for rheumatoid arthritis emphasize NSAID use as symptomatic therapy and use of disease-modifying anti-rheumatic drug therapy for anti-inflammatory objectives. Thus, the original recommendation for "anti-inflammatory" doses of aspirin now is less easily justified. Aspirin therapy merits reconsideration as adjunctive therapy for the management of rheumatoid arthritis. PMID- 8215752 TI - Symptoms in the community. Prevalence, classification, and psychiatric comorbidity. AB - BACKGROUND: While physical symptoms are the leading reason for outpatient visits, a substantial proportion of physical complaints and "minor" illnesses remain poorly understood. The purpose of our study was to determine the prevalence, patient-attributed cause, and psychiatric comorbidity of symptoms in a general population. METHODS: We analyzed data on 13,538 individuals interviewed in the Epidemiologic Catchment Area Program, a multicommunity mental health survey that used the Diagnostic Interview Schedule to determine the prevalence of psychiatric disorders. The Diagnostic Interview Schedule inquires about 38 physical symptoms and includes a probing scheme to classify symptom severity and potential cause. We focused on 26 symptoms most germane to primary care. RESULTS: Of the 26 symptoms, 24 had been problems for more than 10% of persons at some point in their life, with the most common nonmenstrual symptoms being joint pains (36.7%), back pain (31.5%), headaches (24.9%), chest pain (24.6%), arm or leg pain (24.3%), abdominal pain (23.6%), fatigue (23.6%), and dizziness (23.2%). Most symptoms (84%) were at some point considered major in that they interfered with routine activities or had led individuals to take medications or visit a physician. Nearly one third of symptoms were either psychiatric or unexplained, and most symptoms were associated with at least a twofold increased lifetime risk of a common psychiatric disorder. CONCLUSION: Symptoms in the community are prevalent as well as bothersome. Often lacking an apparent physical explanation, such symptoms are associated with an increased likelihood of psychiatric disorders. PMID- 8215753 TI - Do clinical and formal assessments of the capacity of patients in the intensive care unit to make decisions agree? AB - BACKGROUND: The complex environment and technology of intensive care unit (ICU) care may impair the ability of patients to participate in medical decision making or give informed consent. We studied the agreement of the intuitive assessments of residents and nurses of ICU patients' cognition, judgment, and decision-making capacity, and whether those assessments agreed with abbreviated formal mental status testing. METHODS: Using a prospective survey case study, we assessed 200 English-speaking patients within 24 hours of their ICU admission. Formal assessment of cognition, judgment, and insight was performed by a research assistant. We obtained independent intuitive ratings by nurses and residents of patient cognition, judgment, and ability to participate in medical decision making or give informed consent. RESULTS: Residents' and nurses' assessment of cognition and judgment showed a high degree of agreement with weighted ks of greater than 0.76. Assessments of cognition by residents and nurses agreed with Folstein Mini-Mental State Examination in 70% and 73.6% of cases, respectively. Forty percent of the population had an unimpaired Mini-Mental State Examination score of greater than 23, and an additional 12% of the subjects were mildly impaired with scores of 20 to 23. When asked whether they would approach patient or family for consent for an invasive procedure, nurses and physicians said they would request informed consent from 66% and 62% of the patients, respectively. CONCLUSIONS: Residents and nurses caring for patients newly admitted to the ICU agree in their assessment of cognition, judgment, and capacity to participate in medical decision making, and are not unduly influenced by ventilator status. Their assessments correlate highly with abbreviated formal mental status testing. PMID- 8215754 TI - Trends in nonfatal coronary heart disease in the United States, 1980 through 1989. AB - BACKGROUND: Although coronary heart disease mortality has been decreasing, little is known about trends in morbidity from coronary heart disease. We evaluated trends in nonfatal coronary heart disease in the United States during 1980 through 1989. METHODS: We analyzed data from the National Health Interview Survey, an ongoing survey of representative samples of the civilian, noninstitutionalized population of the United States. Survey respondents were determined to have coronary heart disease if they reported ever having a myocardial infarction or heart attack, angina pectoris, or coronary heart disease. Incidence was defined as initial onset of a coronary heart disease condition during the year preceding the interview date. RESULTS: About 6 million people were estimated to be living with coronary heart disease. The age standardized prevalence was relatively constant at about 25 per 1000. Among white men, however, prevalence increased significantly over the 10-year period. Among 75- to 84-year-old men, prevalence increased from 100 per 1000 in 1980 to 179 per 1000 in 1989. Among men and women 45 to 54 years old, prevalence decreased. Overall, the incidence rate of nonfatal coronary heart disease was relatively flat (at about 3 per 1000 per year after 1983). Among white women, the incidence rate increased from 1.4 to 2.8 per 1000, and by the end of the decade it nearly equaled the incidence rate among white men. CONCLUSIONS: Overall, the burden of nonfatal coronary heart disease remained fairly constant during the 1980s. The trends, however, were not uniform in all population groups. The apparent increasing incidence among women deserves continued monitoring. An encouraging trend is the decreasing prevalence in the younger age groups. PMID- 8215755 TI - Is there a duty to accept Medicare payment? PMID- 8215756 TI - There is a conflict of interest in treating Medicare patients. PMID- 8215757 TI - [Viewing the criminal site in unusual cadaver evidence: concealment, identification, determining time of death and reconstruction]. AB - The three cases presented here (Place of finding: bath tub.: [a] 19 year old, female, stabbed to death, detection six months pm, nearly airtight room--silicon rubber; [b] 56 year old, male, drowning, detection 1.5 months pm. [c] Place of finding: slope, 49 year old, female, polytrauma, detection 3 months pm) are characterized by incomplete mummification, skeletization and colliquation of soft tissue. According to our experience medicolegal examiner's presence is necessary on the scene in order to secure in-situ-findings, to recover the human remains and to arrange a proper transport. The autopsy should be performed in the institute's autopsy-room because of access to better equipment e.g. light, air condition, x-ray, instruments. Under these conditions a high quality of forensic examination, improved training of students and police-officers and the dignity of the deceased can be maintained. PMID- 8215758 TI - [Physical restraints and gagging in unnatural death]. AB - Practices of binding and gagging can be found in different types of unnatural death; three case reports concerning fatal autoeroticism, suicide and homicide are presented. In such cases investigations are usually concentrated on the question whether binding and gagging could be carried out by the persons themselves. Loosely bound final loops, especially of the hands, missing local haemorrhages and the discovery of binding instructions support the assumption of self-binding. Accompanying injuries and the entire situation must be taken into special consideration. PMID- 8215759 TI - [Manifestations of screwdriver injuries]. AB - Report on three homicides, in which apart from other kinds of mechanical traumas there were also injuries due to stabs with a screwdriver; in one case a screwdriver with a cross-shaped tip was used; in the two other cases the weapon was a regular blade screwdriver with a single-edged tip. Supplementing the systematic studies by Brinkmann and Kleiber (Arch. Kriminol. 161, 31-40 [1978]) several other findings concerning screwdriver injuries are reported; non penetrating impact lesions of the skin with contusion of the underlying subcutis, reddish streaks consisting of intracutaneous hemorrhages in the width of the screwdriver tip (after tangential slipping), bone lesions typical of the tool. If certain locations are hit (e.g. the region of the ear) piercing injuries are also possible. Injuries of the hands show that the victim tried to defend himself and that the stab was inflicted while the victim was still able to act. PMID- 8215760 TI - [A possibility for verifying condom use in sex offenses]. AB - In order to elucidate the circumstances of sexual crimes, the forensic laboratory is increasingly forced to consider whether the offender has used a condom. The detection presented here depends on Lycopodium spores used in several condom coatings. They can easily be detected e.g. in vaginal swabs. A screening of 40 various condoms available in Germany revealed that 32 (= 80%) were coated with Lycopodium spores. The microscopical investigation of the spores is explained and some sources of error in interpretation are discussed. PMID- 8215761 TI - [Wound ballistics of extremely short-range shotguns]. AB - A 45-year-old man died from a homicidal shotgun wound of the neck. The autopsy showed that the plastic shell retaining cup had entered the body after the mass of the shot; the dispersion of the individual pellets was about 12 cm already. The perpetrator had used a conventional signal pistol equipped with a hand-made steel barrel, gauge 12, length 20 cm, and ammunition with 3 mm pellets (shot no. 5). By means of experimental shots with a similar weapon it could be proved that the entire shot including the plastic shell retaining cup can penetrate the skin at a muzzle-victim range of less than 2 m. PMID- 8215762 TI - [Late potentials and mitral valve prolapse]. AB - Signal averaged electrocardiogrammes were recorded in 100 consecutive patients with echocardiographic mitral valve prolapse (MVP) and compared with 50 normal control subjects. Criteria of normality were defined in the reference population: QRS duration after averaging < 113 ms, Simson's vector of the last 40 ms (RMS40) > or = 17 microV, and duration of the terminal potential within the 40 microV range < 38 ms, using a high-pass bidirectional 40 Hz filter. Of the 100 patients with MVP, late ventricular potentials (LP) were recorded in 38 cases with at least 2 criteria of positivity, compared to only 3 out of 50 (6%) in the control group (p < 0.01). The prevalence of LP was very dependent on the appearances of the valve; when the valve was of normal thickness and only showed slight systolic bulging there were only 5/46 cases of LP (10.9%) which did not differ significantly from the control group. On the other hand, when the valve showed myxoid changes, the prevalence of LP was very high: 33/54 = 61% (p < 0.001 versus controls). Six patients had severe ventricular arrhythmias (sustained ventricular tachycardia or ventricular fibrillation): all had LP. In cases of MVP with frequent ventricular extrasystoles (VEs) the prevalence of LP was the same with normal valves (2/23 = 9% and 2/22 = 9%, NS) whereas LPs were more common in cases of VEs with myxoid valve (23/33 = 70% versus 5/16 = 31%; p = 0.01). The high prevalence of LP in MVP with myxoid valves is a convincing argument in favour of myocardial abnormality in this disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215763 TI - [Comparison of hospital prevalence of rheumatic heart diseases and acute rheumatic arthritis in France and Africa]. AB - This study reports the results of a multicentre enquiry performed in France in 1990 which included 41,242 adults hospitalised in Cardiology Units, 33,907 children hospitalised in Pediatric departments and 8,868 soldiers. A comparative enquiry was also carried out in North Africa (Tunis) and West Africa (Abidjan, Ouagadougou). The results of the French arm of the enquiry showed that rheumatic heart disease (RHD) has become very rare in adults (3.1% of all cardiac disease) and that it tends to occur in older subjects (average 54.4 years of age). There is practically no RHD in young adults. This decreased prevalence of RHD is confirmed in children in whom this diagnosis represents only 0.04% of cases of all cardiac disease--of which 87.5% are of extra-European origin. In contrast, there is a high frequency of RHD in Tunisia (29.3%) and West Africa (13.2% in Abidjan and 13% in Ouagadougou). The disease remains active as is shown by the age of affected adults in Africa (average 21 and 27 years of age). The results also show a reduction to a very low prevalence of acute rheumatic fever in French pediatric departments (0.005%). The authors discuss the reasons for the persistence of endemic infection in Africa: virulence of the streptococcus, predisposing factors (HLA group?), geographic factors and, above all, socioeconomic factors and difficulties in obtaining treatment and prophylaxis. A movement of international cooperation is suggested in order to combat RHD in Africa, especially with regards to its prevention in childhood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215764 TI - [Contribution of antimyosin antibody myocardial scintigraphy in the diagnosis of acute myocarditis]. AB - The authors report three cases of acute myocarditis: the first patient was a 23 year old woman treated for tuberculosis who presented with rapidly progressive congestive cardiac failure. The second patient was a 52 year old man with atypical chest pain and the third was a 55 year old woman presenting as an acute myocardial infarction. In all three cases, a positive antimyosin antibody myocardial scintigraphy supported the presumptive diagnosis. The authors review the principles of the method and its potential indications, antimyosin antibody scintigraphy being able to demonstrate recent myocardial necrosis but not to identify the cause. The sensitivity of the technique is high (83 to 100% according to the series) but the specificity is much lower (about 55%) compared with endomyocardial biopsy, an investigation which is specific but not very sensitive. Modifications of the antibody and the radioactive tracer used at present should improve the diagnostic value of the technique in the near future. PMID- 8215765 TI - [Radiofrequency ablation of Kent's pathways. Apropos of 30 cases]. AB - Radiofrequency catheter ablation is a modern radical treatment of the Wolff Parkinson-White (WPW) syndrome. The authors report their experience of this method in 30 consecutive patients (12 women, 18 men, mean age 34.2 +/- 13 years, range 14 and 63 years) with the WPW syndrome poorly controlled by antiarrhythmic therapy in 27 out of 30 cases. An average of 10.1 applications (1-33) was necessary to suppress anterograde and retrograde conduction in 26 of the 30 patients during the first session (87% success rate). At the time of effective ablation, the average atrioventricular interval was 41 ms (35-55) and in the two patients with a retrograde Kent bundle, the average ventriculoatrial interval was 72 ms (70 and 75 ms). The average duration of the procedure was 3.5 hours (45 mins to 7 hours) with an average fluoroscopy time of 61.6 minutes (9-182 minutes). There were four complications: one pneumothorax, one subacute femoral arterial obstruction and in two patients with a left Kent bundle, one TIA which regressed within 1 hour and one hemiplegia which regressed in 24 hours. After an average follow-up period of 8.3 months (2-16 months) the 26 patients are asymptomatic without any treatment. Radiofrequency catheter ablation therefore seems to be an effective method with a low morbidity for the radical treatment of symptomatic or high risk WPW syndromes. PMID- 8215766 TI - [Postmortem diagnosis of cardiac amyloidosis in the aged. Anatomoclinical correlation]. AB - The absence of specific clinical signs makes the diagnosis of cardiac amyloidosis difficult. Moreover, it is established that this condition, the prevalence of which increases with age, aggravates the prognosis of cardiac failure. The present study was undertaken to identify the clinical or paraclinical signs enabling more accurate diagnosis of this disease. Analysis of 2589 autopsy reports from the University Institutes of Geriatrics of Geneva between January 1972 and January 1990 recensed 58 cases of microscopic cardiac amyloidosis, but this diagnosis was not made in any of these patients before death. Of the potential indicators, the good specificity but poor sensitivity of atrial fibrillation and low voltage electrocardiogram was confirmed. On the other hand, the author's research found the association of radiological cardiomegaly and a raised erythrocyte sedimentation rate in nearly 70% of cases of cardiac amyloidosis with a false positive rate of only 10% in a control group. PMID- 8215767 TI - [Preservation of the aortic valve in acute dissection of the ascending aorta]. AB - The aim of this study was to evaluate the status of the native aortic valve in patients operated for acute dissection of the ascending. aorta (ADAA). Between November 1972 and November 1991, 93 patients were operated for ADAA. There were 76 men and 17 women (average age 54 +/- 12 years). The aortic valve was reserved in 80 cases (86%). In 13 patients (14%) aortic valve replacement was associated with replacement of the ascending aorta. The early mortality was 29% (27/93). The global actuarial survival rates at 5, 10 and 15 years were 60.2 +/- 5.2%, 49.7 +/ 6.1% and 26.9 +/- 9.9% respectively. Fifty patients (94%) in whom the native aortic valve was preserved were followed up. Nine patients (18%) died and average of 97 +/- 46 months after surgery. The causes of death were aortic rupture or extension of the dissection (N = 4), ischemic cardiac failure (N = 2), renal failure (N = 1), cerebrovascular accident (N = 1) and sudden death (N = 1). Forty one patients underwent transthoracic echocardiography. Seven patients developed severe aortic regurgitation, 6 of whom had to be reoperated for aortic valve replacement. Echocardiography showed absence of of minimal aortic regurgitation in 22 cases and mild aortic regurgitation with normal left ventricular function in 12 cases (in 2 cases, aortic valve replacement was associated with surgical treatment of another valvular lesion or of coronary artery disease). Therefore, aortic valve replacement was performed in 8 patients 61.5 +/- 51.2 months after the initial operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215768 TI - [Contribution of transesophageal echocardiography in the diagnosis of intra- and para-cardiac masses]. AB - The authors detected 59 thrombi and 7 intra- or paracardiac tumors in 58 patients in a series of 1,100 transesophageal echocardiography. Twenty-six of the 51 patients with a thrombus were in sinus rhythm; 25 had atrial fibrillation. In 44 cases, the thrombus was single and in 7 cases there were multiple thrombi. A phenomenon of spontaneous contrast in the left atrium was observed in 24 patients (47%). In 31 cases (53%) the thrombi were located in the left auricle, in 21 cases (36%) in the left atrium, in 4 cases in the left ventricle and in 3 cases in the right atrium. Transthoracic echocardiography only detected 25% of these thrombi. The superiority of transesophageal echocardiography was particularly evident for the detection of thrombi in the left auricle (31 by transesophageal echocardiography versus 2 by transthoracic echocardiography) and in the left atrium (13 by transesophageal echocardiography versus 7 by transthoracic echocardiography). Five myxomas were diagnosed by transesophageal echocardiography and 4 of them were identified by transthoracic echocardiography. The site of implantation of the tumor was located in all 5 cases by transesophageal echocardiography. Two right paracardiac tumours were only visible by transesophageal echocardiography. Transesophageal echocardiography is therefore very useful in the diagnosis of thrombi in the left atrium and auricle, of rare hypodense myxomas and paracardiac tumors. In addition, it enables precise localisation of the site of implantation of nearly all intracardiac tumors. PMID- 8215769 TI - [Measurement of cardiac output by CO2 rebreathing technique. A study of reproducibility in the normal subject; application to cardiac insufficiency]. AB - A feasibility and reproducibility study of cardiac output measurement by CO2 rebreathing was performed in normal subjects and in patients with compensated cardiac failure. The measurements were performed at rest and at the second stage of the Bruce protocol in normal subjects (N = 12) with a good reproducibility (r = 0.81) after an interval of two days. In patients with stable cardiac failure (N = 17), the cardiac outputs were 9.4 +/- 3.9 l/min and 9.3 +/- 3.1 l/min by measuring the arterial pCO2 and end-expiratory CO2 compared with the theoretical value of 9.9 +/- 2 l/min. The non-invasive measurement of cardiac output by the CO2 rebreathing method was well tolerated by patients and is reliable and reproducible. PMID- 8215770 TI - [Physiopathology of myocardial dysfunction in septic shock]. AB - Left ventricular dysfunction is rarely a prominent feature of septic shock. Initially, it is masked by circulatory changes and adaptive phenomena which increase the cardiac output. Evaluation of intrinsic myocardial function is therefore difficult in this pathology. The different experimental models used (cell culture, isolated muscle, isolated perfused heart and whole animal) and recent clinical studies using angiographic, catheter and echocardiographic data, have confirmed that this condition exists. Its physiopathology is not yet fully understood and involves several mediators. The direct effect of bacterial endotoxins has not been formally established. However, therapy with anti endotoxin antibodies does give encouraging results. The cytokines, such as interleukin-1, tumour necrosis factor, and platelet activating factor play a key role between the infectious factors and cellular mediators. Their effects on the myocardium are subject of much on-going research. Current date, in particular with respect to the tumour necrosis factor, suggest that they may have a direct cardiodepressor factor. The presence of a circulating negative inotropic substance has been suspected for many years. Recent studies tend to confirm this hypothesis though the substance itself has not yet been isolated. The theory of reduced coronary flow causing myocardial dysfunction in septic shock has fallen out of favour. Some experimental evidence supports the clinical impression of reduced vascular and cardiac reactivity to catecholaminergic stimulation. The actions of different membrane structures involved have not been determined. At cellular level, changes in calcium metabolism, which regulates muscle contraction and relaxation, probably play an important role in septic shock. In addition to the symptomatic therapeutic advances that have been made in septic shock, specific myocardial treatment could be beneficial. PMID- 8215771 TI - [Value of transesophageal echography in the diagnosis of posterior ventricular septal rupture during the acute phase of myocardial infarction. Apropos of 2 cases]. AB - The authors report two cases of posterior ventricular septal defects complicating acute myocardial infarction diagnosed by transesophageal echocardiography. Transesophageal echocardiography was well tolerated confirmed the diagnosis, and enabled accurate evaluation of the shunt in the transgastric view. The anatomical results guided the surgical approach and correlated well with the operative findings. PMID- 8215772 TI - [Holter and sudden death: value in a case of arrhythmogenic right ventricular dysplasia]. AB - The authors report the first case of arrhythmogenic right ventricular dysplasia presenting with a sudden death due to primary ventricular fibrillation (ventricular fibrillation not preceded by ventricular tachycardia) recorded by the Holter method. The patient was a 56 year old man whose only complaint was near syncopal case is the fact that it is the first documented case of ventricular fibrillation revealing arrhythmogenic right ventricular dysplasia, the diagnosis of which was made at autopsy. In addition, the Holter recording showed the factors which triggered the arrhythmia: the "trigger" of 4 monomorphic ventricular extrasystoles during the minute preceding the ventricular fibrillation; the arrhythmogenic substrate giving rise to late ventricular potentials and, finally, the analysis of the R-R intervals suggesting a role of the sympathetic and parasympathetic nervous systems. Holter recordings could help identify subjects at high risk of severe ventricular arrhythmias. PMID- 8215773 TI - [Congestive cardiac failure secondary to hepatico-portal arteriovenous fistula. Apropos of a case and review of the literature]. AB - A 66 year old man with mild hypertension developed congestive cardiac failure of rapid onset associated with a continuous epigastric murmur suggesting an arteriovenous fistula. Doppler ultrasonography, computed tomography, magnetic resonance imaging and abdominal arteriography showed the fistula to arise from a large thrombosed aneurysm of the hepatic artery which had ruptured into the portal vein. Echocardiography and radionuclide angiography showed normal left ventricular systolic function. The patient underwent aneurysmorrhaphy and suture of the portal vein without any complications and the murmur and signs of cardiac failure disappeared. Histological examination showed the arterial lesion to be due to atherosclerosis. The authors underline the rarity of aneurysms of the hepatic artery and, above all, of their rupture into the portal system as there have only been 7 previously reported cases. Fistulae of the portal system are usually well tolerated, the commonest complication being portal hypertension. Cardiac failure is an exceptionally rare occurrence: it may be observed when the fistula develops suddenly and has a high flow rate, and in patients with abnormal myocardial function. PMID- 8215774 TI - [False traumatic aneurysm of the internal mammary artery caused by a stab wound. Apropos of a case]. AB - The authors report the case of embolism by a false aneurysm of the internal mammary artery: a 57 years old woman with no previous medical history was admitted to the emergency unit with a kitchen knife stuck in the 3rd left intercostal space. After withdrawing the knife, in the operating theatre, radiological controls revealed a blurred opacity in the left antero-superior mediastinum. The patient signed her own discharge from hospital against medical advice on the 7th day. She was readmitted 10 months later for left retrosternal chest pains. Chest X ray demonstrated a rounded opacity in the antero-superior mediastinum. Computed tomography with injection of contrast confirmed the vascular nature of the opacity. Arteriography in the aortic arch confirmed the diagnosis of false aneurysm of the left internal mammary artery. Selective angiography of the internal mammary artery was undertaken and the aneurysm was embolised with coils. The clinical outcome was immediately improved with relief from the chest pains. PMID- 8215775 TI - [Robert de Vernejoul (1890-1992)]. PMID- 8215776 TI - [Tools of molecular biology, what can be expected from them?]. AB - The techniques of molecular biology represent a new tool for research and diagnosis. They have been used routinely since the middle 80s. The first applications were mainly in hereditary diseases. These techniques investigated an information and not direct biological activity and so new strategies had to be developed. Two techniques have played key roles. They are Southern's method which enables the detection of specific sequences among DNA fragments in any individual within a few days, and the method of in vitro selective amplification (PCR) which is the equivalent of cloning a sequence of several hundred pairs of bases in any individual in less than 3 hours. In hereditary diseases, molecular biological techniques enable diagnosis of the genetic abnormality responsible for the condition, even when the defect is not known. To this end, two strategies are available. The first, and the most satisfactory, is the direct strategy of characterising the genetic defect itself. This is possible when the mutation is a major alteration of the DNA molecule such as a deletion, an insertion or a recombination or when the mutation is isolated and known. In other cases, an indirect approach may be used which consists of determining whether the subject has received normal or defective chromosomes from his or her parents. The identification of good or bad chromosomes is based on the study of DNA markers: polymorphism. The indirect strategy can only be used under certain conditions: presence of an index case, informativity of polymorphisms, complete family study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215777 TI - [Inflammatory mechanisms of atherosclerosis: pathogenic and etiologic inferences]. AB - Inflammation is the reaction of a vascularized living tissue to local injury. At its chronic stage, inflammation displays 4 characteristic features that are all to be found in atherosclerotic plaques: lympho-monocytic infiltration; sclerosis; cellular proliferation; vascular proliferation. This view sheds new light and opens new avenues for research on atherosclerosis. That is true for pathogenesis which progressively integrates the mass of information that has accumulated about the cellular and molecular mechanisms of inflammation. That is also true fort the aetiology of atherosclerosis where the causal enigmas are approached with a more open mind, much wider than the traditional concepts of degeneration and overloading that have prevailed for so long. In the near future, some promising therapeutic clues should derive from this renewed approach of atherosclerosis. PMID- 8215778 TI - [Regression of coronary atherosclerosis evaluated by angiography. A review of principal trials and critical study]. AB - The concepts of acceleration of atherosclerosis with fat rich diets and the regression or at least stabilisation of atherosclerosis by suppressing the cholesterol, introducing exercise programmes or administering calcium antagonists or aspirin, have been validated in the animal model. In the clinical situation, repeat coronary angiography has demonstrated that hyperlipidemia and the interval between two investigations are the main factors influencing the progression of atherosclerosis. However, the factors underlying the appearance and progression of atheromatous plaques remain unknown. Interventional trials based on the principle of introducing treatment after reference angiography have been undertaken. The results were assessed after variable time intervals. The general conclusion is that there is a direct relationship between the lowering of plasma cholesterol, the intensity of exercise and the slowing of progression of atherosclerosis as far as can be evaluated by repeat angiography. The data concerning the effect of calcium antagonists is confusing. The main criticism of these trials is the instrument of measurement and the practical significance or even the reality of the observed changes. In the present state of our knowledge, trials of the regression of atherosclerosis can not replace longitudinal studies of the long-term effects of drugs on cardiovascular and general morbidity and mortality. PMID- 8215779 TI - [Molecular mechanisms controlling cellular proliferation in the vascular system]. AB - Molecular biological techniques and the study of models allowing elementary analysis have helped to identify the molecular mechanisms controlling cellular proliferation, products of oncogenes and anti-oncogenes and the proteins interacting with these compounds, or the elements of the cytoplasmic clock which controls the cellular cycle. However, analysis of model systems does not always correspond to what happens in vivo where a regulating molecule may have several functions and where certain controls are superfluous. Therefore, the angiogenic factors identified by their action on endothelial cells in vitro and in model systems in vivo are multifunctional molecules. Their expression and that of their receptors are not always associated with angiogenesis in normal or pathological conditions. Similarly, the responses of endothelial cells to these angiogenic factors are not the same in vivo and in culture plates. The authors discuss in more detail the role of the C-ets-1 oncogene which expresses itself in endothelial cells during angiogenesis. The C-ets-1 protein is a transcription factor which may control the expression of genes coding proteases which degrade the extracellular matrix. The description of the role of this molecule in the network controlling angiogenesis should enable the definition or evaluation of therapeutic actions targetting this process. PMID- 8215780 TI - [Restenosis after coronary angioplasty. Contribution of experimental models]. AB - Restenosis is the main complication of coronary angioplasty. Many experimental models have been developed over the last few years, reflecting very active research work in this field. The value of experimental models may be discussed under two headings: improvement in our understanding of the mechanisms of restenosis and the development of preventing strategies. The smooth muscle cell is the main cause of restenosis, experimental models having demonstrated a triple response which has been observed clinically: proliferation, migration to the intima and synthesis of the extracellular matrix. The mechanisms controlling this response are not fully understood, the most likely candidates being desendethelialisation, platelets and other circulating components of the blood, vasopressive hormones especially the renin-angiotensin system, growth factors and finally the degree of direct trauma to the smooth muscle cells. Experimental models also allow evaluation of therapeutic strategies elaborated to reduce the frequency of restenosis in clinical practice: three strategies are identifiable: systemic treatment, local treatment and genetic therapy. At the present time, none of these approaches has been clearly shown to be effective clinically though some positive results have been observed in the animal. PMID- 8215781 TI - [The clinician's view of restenosis: methodological and therapeutic aspects]. AB - The study of restenosis after angioplasty poses serious methodological problems. The first is the definition of angiographic criteria of restenosis. These should be based on quantitative angiographic measurements in absolute values of coronary diameter rather than on the use of percentage stenosis which is an inaccurate indication of the true severity of the coronary disease. Moreover, the use of an arbitrary threshold > or = 50% stenosis at angiographic control tends to "pre select" poor initial results of angioplasty as restenosis. Criteria based on absolute values of coronary artery diameter have enabled the demonstration of a close correlation between an excellent result of angioplasty and the degree of the restenosis 6 months later which suggests that a too good result of angioplasty may be related to increased intimal hyperplasia. This is a real dilemma for those performing angioplasty knowing that a mediocre initial result does not guarantee a good long-term result. In addition, it seems that the diameters of coronary arteries 6 months after angioplasty have a Gaussian distribution. This would imply that intimal hyperplasia is a constant phenomenon after angioplasty and that it is its degree which varies between patients with and without restenosis. Restenosis would therefore be more of a quantitative than a qualitative phenomenon. This justifies the use of continuous variables in the study of restenosis and a categorical approach would therefore be less valuable, not as powerful statistically and based on thresholds of an arbitrary nature. This could also explain the contradictory results concerning predictive factors of restenosis in the literature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215782 TI - [Mechanisms of vascular hypertrophy in hypertension]. AB - In hypertension, the thickening of the arterial wall by an increase in the cellular mass and collagen and elastin content may be considered to be an adaptive response to the high blood pressure. Positive and negative feedback systems play a role in the hypertension-vascular hypertrophy couple. Increased wall stress associated with stretching of the smooth muscle acts as a mechanical agonist of cellular growth in synergy with plasma or autocrine growth factors. In general, vascular hypertrophy ceases when the stress returns to normal. However, the increase in cell mass may result in an increase in systemic vascular resistance due to muscular hypertonicity and lead to an amplification of the hypertensive condition. The mechanisms of mechano-transduction are not fully understood. Moreover, genetic vascular changes affecting the structure of the vessels, the sensitivity to vasoactive substances or the geometry of the vascular system can also induce hypertension. PMID- 8215783 TI - [Left ventricular hypertrophy: molecular aspects]. AB - The expression of genes changes during left ventricular hypertrophy. These changes are known as mechanogenic transduction. With respect to the two main contractile proteins, myosin and actin, this is due to a differential expression of their respective multigenic families. Changes of isoform are uncoordinated in time and space. It is important to recognise that the genes themselves are normal and that it is their regulation which is disturbed. Recent data shows that, under normal conditions, the regulation occurs at the transcription stage. A fuller understanding of these mechanisms is necessary if we are to comprehend the pathogenesis of cardiac hypertrophy and failure. PMID- 8215784 TI - [Left ventricular hypertrophy: a real compensatory mechanism?]. AB - Our understanding of left ventricular hypertrophy has increased considerably in recent years with the introduction of new investigative techniques and the publication of clinical and epidemiological studies. The mechanism of the genesis of LVH is complex and multifactorial: besides the purely mechanical explanation which places LVH in a purely compensatory complex, counteracting the increase in left ventricular load, many other factors have been incriminated including a genetic predisposition and neurohormonal activation. A long phase of compensation is followed by ventricular insufficiency and cardiac failure. In addition, LVH has been identified as an independent cardiovascular risk factor for increased morbidity and mortality. Partial regression of LVH after surgical correction of valvular disease and especially after treatment with certain antihypertensive drugs, should be considered with great interest, even though the long-term prognosis of this regression remains uncertain. PMID- 8215785 TI - [Virus and dilated cardiomyopathies]. AB - Dilated cardiomyopathy is so called when an etiological investigation is negative and no cause can be found for ventricular dilatation-hypokinesia. Current research points to genetic, immunological and infectious factors, often associated, and the passage of subclinical viral myocarditis to chronic disease. There is a lot of evidence in favour of this hypothesis. In the experimental model, the relationship between viral myocarditis and dilated cardiomyopathy has been demonstrated with, as cofactors, a genetic predisposition and an immunitary deficiency leading to an auto-immune subacute myocarditis. In the clinical setting, the enterovirus with a high cardiac tropism seems to play an epidemiological role in the genesis of dilated cardiomyopathy. The concentrations of neutralising anti-coxsackie B virus antibodies is higher in subjects with dilated cardiomyopathy than in a control population. The frequency of lymphocytic infiltration, a marker of dysimmunitary myocarditis, is variable from study to study but the presence of sequences of enterovirus genome in the myocardium could explain slow replication of the virus progressively destroying the myocytes. Techniques of molecular hybridization with or without prior genic amplification by the "Polymerase Chain Reaction" have demonstrated such sequences of specific enterovirus genome but discordant results require further studies. PMID- 8215786 TI - [Cardiomyopathies during acquired immunodeficiency syndrome]. AB - Myocardial involvement in the acquired immunodeficiency syndrome is well established on clinical data, echocardiographic studies, macropathological findings and histological studies on autopsy or endomyocardial biopsy specimens. The condition may present with asymptomatic left ventricular dysfunction with a low ejection fraction, acute or subacute myocarditis or cardiac failure and dilated cardiomyopathy. A few cases of hypertrophic cardiomyopathy with HIV infection have also been reported. PMID- 8215787 TI - [Functional classification of cardiac insufficiency]. AB - Several systems have been proposed for assessing the degree of functional impairment of chronic cardiac failure in order to be able to compare patients and to appreciate progression of the condition in individual patients. The NYHA classification is subjective, not very reproducible, and does not provide a good prediction of exercise capacity. The Canadian classification is not much better. Feinstein's classification is too complex, impractical and has never been validated. The specific activity scale proposed by Goldman indicates the degree of functional incapacity by comparison with activities of everyday life selected for their variability and classified according to the effort required to perform them. This classification has a good reproducibility and correlates well with exercise stress testing (exercise duration, VO2 max). However, it is not particularly well suited to the French population. The examples are not very precise; in addition, contradictions are possible, making it difficult to classify some patients. The authors propose a specific activity scale adapted for French patients. This classification was studied in 45 patients with chronic primary dilated cardiomyopathy. It was reproducible and correlated well with peak VO2. The progressive design of the symptom questionnaire avoids contradiction. This classification could be useful both in everyday practice and for multicentre research studies. PMID- 8215788 TI - [Should cardiac insufficiency be first treated by angiotensin converting enzyme inhibitors?]. AB - Chronic cardiac failure is an important problem of public health because of its prevalence and high mortality. A better understanding of its physiopathology and the detrimental effect of neurohormonal activation that it induces were the reasons for the utilisation of angiotensin converting enzyme inhibitors leading to symptomatic improvement and also a reduction in the mortality of severe cardiac failure, as demonstrated in the CONSENSUS study published 5 years ago. Since then, cardiologists have presented ACE inhibitors in all stages of cardiac failure, but is this attitude justified? More explicitly, are ACE inhibitors the drugs of choice in cardiac failure? Before acknowledging this label "drug of choice" in the treatment of chronic cardiac failure, ACE inhibitors should fulfill certain reference criteria proposed by Packer for the treatment of this condition: rapid relief of symptoms; reduced mortality; modification of the natural history of the condition; efficacious and well tolerated. The effects of ACE inhibitors are analysed critically taking into account the results of large scale therapeutic trials (SOLVD, V-HeFT II, CONSENSUS II, SAVE), which have been reported recently? The reported results confirm clinical impressions: ACE inhibitors are the drugs of choice of all stages of chronic cardiac failure but in association with diuretic and digitalis therapy. PMID- 8215789 TI - [Biological bases of ventricular remodeling]. AB - Cardiac hypertrophy commonly observed in clinical practice is not a disease but a physiological reaction to disease, usually hypertensive or coronary. It involves changes in gene expression, often species specific, which account for the thermodynamic adaptation of the cardiac muscle to new conditions of load; some of these changes may have deleterious effects and explain changes in diastolic compliance and the arrhythmogenicity of hypertrophied hearts. The most important changes are in the myosin content and certain membrane proteins. Many hormonal factors also play a role in ventricular remodeling including angiotensin II and, independently, aldosterone. PMID- 8215790 TI - [Protective effects of perindopril in an experimental model of cardiomyopathy]. AB - The effects of an angiotensin converting enzyme (ACE) inhibitor on the intrinsic contractility of the myocardium in cardiac failure have not been studied intensively. The authors studied inotropism, lusitropism and economy of contraction in vitro on left ventricular papillary muscle preparations of cardiomyopathic Syrian hamsters (CSH) treated preventively with perindropil, i.e. before overt signs of cardiac failure. The CSH of the dilated Bio 53.58 strain aged 1 month were treated with perindropil 1 mg/Kg/day for 5 months (PE, N = 11) or with placebo (PL, N = 11) and control hamsters of the F1B strain received placebo (C, N = 7). Compared with C, PL had a significant reduction of the maximal velocity of contraction Vmax (p < 0.01) and of total isometric tension (TF/mm2), p < 0.05, and a reduction of the G curve of the hyperbolic Hill Force Velocity relationship (p < 0.01). The G value is usually greater in models with improved economy of contraction. When compared with PL, PE showed a 68% inhibition of the plasma activity of ACE, a better Vmax (p < 0.05) but an unchanged TF/mm2. The G value was less depressed than that of C (p < 0.05). The velocity of isotonic relaxation (maxVL) and the negative peak of the derivative of the isometric force (-dF/dt max) were significantly lower in the PL than in the C group but these lusitropic abnormalities remained coordinated with those of the contraction phase, indicating the absence of an intrinsic effect on relaxation in cardiomyopathy. Perindopril prevented the reduction of maxVL but not that of -dF/dt max.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215791 TI - [Cardiotoxicity of anthracyclines]. AB - The only factor limiting the use of anthracyclines (very powerful antimitotic antibiotics) is their cardiotoxicity. The cardiac involvement is irreversible, dose-dependent and may be detected at an early stage by non-invasive (echocardiography, myocardial scintigraphy) or invasive investigations (endomyocardial biopsy). The mechanism of cardiac toxicity involves the oxidative metabolism of the cardiac myocyte and liberation of oxygen free radicals and is different from the antitumoral effect. Protocols of administration over 6 to 24 hours have enabled the use of higher total doses and the reduction of cardiotoxicity without affecting the therapeutic efficacy. The use of "antioxidants" such as ICRF 187 has given promising results in myocardial protection. The strategy of surveillance (screening) of cardiotoxicity, of the mode of administration of the anthracyclines, results from the essential coordination of the efforts of the chemotherapist, taking into account the pathology, the sensitivity of the tumor to anthracyclines therapy, enabling personalization of the prescription and the abandon of the concept of maximal dosage. PMID- 8215792 TI - [French familial multicenter survey of hypertrophic cardiomyopathy. Initial Doppler echocardiographic results]. AB - A French multicentre study of hypertrophic cardiomyopathy has recruited 260 subjects belonging to 18 families. At least 3 persons from each family included had a hypertrophic cardiomyopathy. A Doppler echocardiographic examination was performed in all members of these 18 families. The diagnosis of hypertrophic cardiomyopathy was based on M mode and/or 2D observations of parietal hypertrophy: wall thickness over 13 mm. Asymmetrical forms were distinguished from symmetrical forms by a septum/posterior wall ratio of over 1.3 in M mode or 2D study. The patients had an average age of 40 +/- 18 years, 127 were men and 133 women. One hundred and sixty eight were considered to be normal, 87 had hypertrophic cardiomyopathy and 5 were border line. The maximal diastolic wall thickness on M mode recording of pathological cases was 19.2 +/- 4.8 mm compared with 9.5 +/- 1.9 mm in healthy subjects (p < 0.001). The septum/posterior wall ratio was 1.8 +/- 0.62 in pathological cases and 1.1 +/- 0.8 in normal ones (p < 0.001). Eighty five per cent of the cardiomyopathic cases were asymmetrical (74/87) and only 15% were considered to be symmetrical (13/87) on M mode study whereas 5% were concentric on 2D echocardiography. By Maron's classification, type I hypertrophy was observed in 6% of cases (4/64), type II in 30% (19/64), type III in 58% (37/64), and type IV in 6% (4/64). Signs of obstruction were looked for and systolic anterior motion of the mitral valve was observed in 52% of pathological cases (45/86) and mid-systolic aortic valve closure in 30% (25/83).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215793 TI - [Effects of phosphodiesterase inhibitors on diastolic function]. AB - It has been clearly established that ischemic heart disease, hypertension and ageing affect diastolic function before any change is observed in contractile function. Though an increasingly recognised clinical entity, cardiac failure with normal systolic function still does not have any specific treatment. Phosphodiesterase inhibitors which increase AMPc, in addition to their inotropic and vasodilator effects, accelerate relaxation. Major and isolated abnormalities of relaxation have been demonstrated in vitro in non necrosed tissues of both the dilated and hypertrophic forms of advanced cardiomyopathy. The myocardium seems unable to restore rapidly the low cytosolic calcium concentrations required for the deactivation of the contractile proteins. The underlying mechanisms are probably very complex but a deficit in AMPc production has been demonstrated in very advanced stages of cardiomyopathy. In ischemia, however, the abnormalities of relaxation seem to be directly related to a defect in free energy production inhibiting the sarcoplasmic reticulum calcium pump. If abnormalities of relaxation due to ischemia and those due essentially to a passive mechanism are excluded, phosphodiesterase inhibitors would seem to have pharmacological effects likely to improve diastolic function. Clinical studies confirm the beneficial effects of Milrinone and Enoximone on relaxation and the rapid phase of diastolic filling, both in acute and chronic studies. However, it has not yet been clearly established whether improved diastolic function is due to a direct action on the myocardium or an indirect action due to improved conditions of load. In order to determine the specific effects of phosphodiesterase inhibitors on diastolic function, further research is required.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215794 TI - [Sudden death and cardiac insufficiency]. AB - The relationship between the incidence of ventricular arrhythmias and sudden death in chronic cardiac failure is, in fact, true as arrhythmias are mainly related to the severity of left ventricular dysfunction. If sudden death in subjects without cardiac failure is usually attributed to arrhythmia, in chronic cardiac failure it is often the result of sudden collapse, the mechanism of which is not well known. The distinction between sudden and non-sudden death therefore loses much of its value. PMID- 8215795 TI - Metabolism of 2-chloro-4-methylphenoxyacetate by Alcaligenes eutrophus JMP 134. AB - 2-Chloro-4-methylphenoxyacetate is not a growth substrate for Alcaligenes eutrophus JMP 134 and JMP 134-1. It is, however, being transformed by enzymes of 2,4-dichlorophenoxyacetic acid metabolism to 2-chloro-4-methyl-cis,cis-muconate, which is converted by enzymatic 1,4-cycloisomerization to 4-carboxymethyl-2 chloro-4-methylmuconolactone as a dead end metabolite. Chemically, only 3,6 cycloisomerization occurs, giving rise to both diastereomers of 4 carboxychloromethyl-3-methylbut-2-en-4-olide. Those lactones harboring a chlorosubstituent on the 4-carboxymethyl side chain were surprisingly stable under physiological as well as acidic conditions. PMID- 8215796 TI - Two N5,N10-methylenetetrahydromethanopterin dehydrogenases in the extreme thermophile Methanopyrus kandleri: characterization of the coenzyme F420 dependent enzyme. AB - It was recently reported that the extreme thermophile Methanopyrus kandleri contains only a H2-forming N5,N10-methylenetetrahydromethanopterin dehydrogenase which uses protons as electron acceptor. We describe here the presence in this Archaeon of a second N5,N10-methylenetetrahydromethanopterin dehydrogenase which is coenzyme F420-dependent. This enzyme was purified and characterized. The enzyme was colourless, had an apparent molecular mass of 300 kDa, an isoelectric point of 3.7 +/- 0.2 and was composed of only one type of subunit of apparent molecular mass of 36 kDa. The enzyme activity increased to an optimum with increasing salt concentrations. Optimal salt concentrations were e.g. 2 M (NH4)2SO4, 2 M Na2HPO4, 1.5 M K2HPO4, and 2 M NaCl. In the absence of salts the enzyme exhibited almost no activity. The salts affected mainly the Vmax rather than the Km of the enzyme. The catalytic mechanism of the dehydrogenase was determined to be of the ternary complex type, in agreement with the finding that the enzyme lacked a chromophoric prosthetic group. In the presence of 1 M (NH4)2SO4 the Vmax was 4000 U/mg (kcat = 2400 s-1) and the Km for N5,N10 methylenetetrahydromethanopterin and for coenzyme F420 were 80 microM and 20 microM, respectively. The enzyme was relatively heat-stable and lost no activity when incubated anaerobically in 50 mM K2HPO4 at 90 degrees C for one hour. The N terminal amino acid sequence was found to be similar to that of the F420 dependent N5,N10-methylenetetrahydromethanopterin dehydrogenase from Methanobacterium thermoautotrophicum, Methanosarcina barkeri, and Archaeoglobus fulgidus. PMID- 8215797 TI - Development of quasi-multicellular bodies of Treponema denticola. AB - The formation of quasi-multicellular bodies of Treponema denticola was analysed using different electron microscopical methods. These bacteria could develop four different conformations: (i) normal helical forms; (ii) twisted spirochetes, forming plaits; (iii) twisted spirochetes,forming club-like structures; (iv) spherical bodies in different size. Treponemes within spherical bodies, plaits, and clubs proved to be enclosed in a common outer sheath in which the normal arrangement of their axial flagella was lost. The development of the quasi multicellular bodies starting from the monoforme spirochetes was elucidated and this morphogenetic process is illustrated by a schematic drawing. Factors which might be involved in the induction of the structures are discussed and their possible pathogenetic importance is considered. PMID- 8215798 TI - A novel type of meso-diaminopimelic acid-based peptidoglycan and novel poly(erythritol phosphate) teichoic acids in cell walls of two coryneform isolates from the surface flora of French cooked cheeses. AB - The primary structure of the peptidoglycan and the teichoic acids of two coryneform isolates from the surface flora of French cooked cheeses, CNRZ 925 and CNRZ 926, have been determined. In the peptidoglycan, meso-diaminopimelic acid was localized in position three of the peptide subunit. It contained an D glutamyl-D-aspartyl interpeptide bridge, connecting meso-diaminopimelic acid and D-alanine residues of adjacent peptide subunits. The alpha-carboxyl group of D glutamic acid in position two of peptide subunits was substituted with glycine amide. The teichoic acid pattern and composition differed between the strains: both contained an erythritol teichoic acid and strain CNRZ 925 also contained an N-acetylglucosaminylphosphate polymer. The erythritol teichoic acids differed in terms of the quality and quantity of substituents, but they both had N,N' diacetyl-2,3-diamino-2,3-dideoxyglucuronic acid in common. PMID- 8215799 TI - Characterization of a restriction barrier and electrotransformation of the cyanobacterium Nostoc PCC 7121. AB - We have investigated host restriction as a barrier to transformation and developed a method for gene transfer into the previously untransformable, heterotrophic cyanobacterium Nostoc PCC 7121. A restriction endonuclease, designated Nsp 7121I, has been partially purified by phosphocellulose chromatography of Nostoc cell extracts. Comparisons of Nsp 7121I digests of bacteriophage lambda and plasmid DNAs with computer-generated restriction fragment profiles showed that Nsp 7121I is an isoschizomer of restriction endonucleases, such as Asu I, Nsp 7524IV, Sau 96I, and Eco 47II, that recognize the sequence GGNCC. Cleavage by Nsp 7121I within this sequence was confirmed by sequence analysis of DNA fragments cleaved at a unique Nsp 7121I site. These data further suggested that cleavage occurs after the first G (5'-G/GNCC-3') in this site to generate a three base 5' overhang. Nsp 7121I degraded all plasmids used in previous transformation attempts but modification of these DNA molecules by Eco 47II methylase effectively prevented digestion by Nsp 7121I. Plasmids premethylated by passage through Escherichia coli carrying a plasmid encoded Eco 47II methylase have now been used in an electroporation procedure to transform Nostoc PCC 7121 to neomycin resistance at frequencies as high as one transformant per 10(3) viable cells. Transformation, and stable replication within Nostoc of one of the transforming plasmids (pRL25), was confirmed by recovery of pRL25, in its original form, from transformants. Conjugal transfer of pRL25 from E. coli into Nostoc was also possible but at much lower efficiency than by electroporation. These findings establish the basis for genetic analysis of Nostoc PCC 7121, from which genes for photosynthetic electron transport have been cloned. PMID- 8215800 TI - Outcome of depression and anxiety in primary care. A three-wave 3 1/2-year study of psychopathology and disability. AB - BACKGROUND: We evaluated the long-term outcome of depression and anxiety and associated disability among primary-care attenders with common psychiatric disorders and symptoms (n = 201) using binary and multicategorical, interview based outcome measures of psychiatric illness and disability. METHODS: A two stage design was used. In the first stage, 1994 consecutive attenders of 25 general practitioners were screened on psychiatric illness with the General Health Questionnaire and by their physicians. A stratified random sample (n = 292) with differing probabilities was selected for second-stage interview (Present State Examination and Groningen Disability Schedule). Patients with psychiatric symptoms (n = 201) were reassessed 1 (n = 182) and 3 1/2 (n = 154) years later. RESULTS: At 1- and 3 1/2-year follow-ups, many cases no longer met the criteria of their baseline diagnosis and disability levels had substantially dropped. However, partial remission, not full recovery, was the rule, and was associated with residual disability. Depression had better outcomes than anxiety and mixed anxiety-depression. CONCLUSIONS: We concluded that a multicategorical, rather than a binary, outcome measure better reflects patient outcomes, since it highlights partial remission, mild symptoms, and residual disability, and as such, stresses the need to supplement short-term treatment. A multicategorical caseness model may be advantageous for research and clinical practice. We suggest a dynamic-equilibrium model to account for residual symptoms and disability. This study is a follow-up to two earlier reports on the recognition, treatment, and 1 year course of common psychiatric illnesses in general practice. PMID- 8215801 TI - The relationship between panic disorder and major depression. A new family study. AB - OBJECTIVE: The comorbidity between panic disorder and major depression (MDD) in individuals has been amply documented. However, data from family studies to determine whether panic disorder and MDD aggregate separately or together in families have been inconclusive, in part because of the absence of studies with the full range of proband groups. This report presents results from a family study with the necessary mutually exclusive groups: panic disorder without MDD, panic disorder with MDD, MDD without panic disorder, and normal controls. METHODS: Diagnostic information was obtained from 193 probands and 1047 of their adult relatives with the Schedule for Affective Disorders and Schizophrenia- Lifetime Version for Anxiety Disorders by direct interview, and/or from multiple informants, without knowledge of proband diagnoses. Best-estimate diagnoses were based on all available information by clinicians independently of data collection and without knowledge of probands' and other relatives' status. RESULTS: Findings indicated the specific and independent transmission of panic disorder and MDD, the separation of panic disorder from MDD, and the nonfamilial nature of late onset MDD. The pattern of results was unaffected by the use of different diagnostic criteria, number of informants, interview status of relatives, presence of substance abuse or agoraphobia or the sequence of MDD and panic disorder in probands, or whether probands were selected from treatment clinics or community sample. CONCLUSIONS: We conclude that panic disorder and MDD are separate disorders with substantial co-occurrence in individuals, and that panic comorbid with MDD is not a single, distinct disorder. Finally, we illustrate an approach to examining comorbidity in family data through analysis of mutually exclusive, parallel diagnoses in probands and relatives. PMID- 8215802 TI - The Roscommon Family Study. III. Schizophrenia-related personality disorders in relatives. AB - OBJECTIVES: We sought to clarify the familial relationship between five putative schizophrenia-related personality disorders (schizotypal [SPD], paranoid, schizoid, avoidant, and borderline) and schizophrenia, other nonaffective psychoses, and affective illness. DESIGN: A case-controlled epidemiologic family study using DSM-III-R criteria. PARTICIPANTS: Five hundred thirty-four probands selected from a psychiatric case register or electoral register, of whom 415 were personally interviewed, and 2043 living and traceable relatives, of whom 1753 were personally interviewed. RESULTS: Compared with relatives of unscreened controls, relatives of probands with schizophrenia had a highly significantly increased prevalence of SPD, and modest, but significant, increased prevalences of paranoid, schizoid, and avoidant personality disorders. Borderline personality disorder was rare, with a modest clustering of cases in relatives of affective disorder probands. The prevalence of SPD was also significantly elevated in relatives of probands with SPD and with other nonaffective psychoses but not in relatives of probands with psychotic or nonpsychotic affective illness. In contrast to the pattern seen for schizophrenia, the prevalence rate of SPD was substantially greater in parents than in siblings of schizophrenic probands. CONCLUSIONS: Schizotypal personality disorder has a strong familial relationship with schizophrenia. Paranoid, schizoid, and avoidant, but not borderline, personality disorders may have a significant familial relationship with schizophrenia. Schizotypal personality disorder also reflects the familial liability to other psychotic disorders but probably not to affective illness. Fitness effects may substantially influence the pattern of schizophrenia-related personality disorders in relatives. PMID- 8215803 TI - A twin study of recent life events and difficulties. AB - OBJECTIVES: To examine the role of genetic and familial-environmental factors in the origin of stressful life events. DESIGN: Self-report questionnaires describing stressful life events in the last year. PARTICIPANTS: Both members of 2315 twin paris ascertained from the population-based Virginia Twin Registry. RESULTS: Life events were modestly but significantly correlated in twin pairs, and correlations in monozygotic (MZ) twins consistently exceeded those in dizygotic (DZ) twins. For total life events, the best-fitting twin model indicated that familial-environmental and genetic factors each accounted for around 20% of the total variance. Individual life events could be best divided into "network events" (directly affecting individuals in the respondent's social network) where twin resemblance was due solely to the familial environment, and "personal" events (directly affecting the response) where most twin resemblance was the result of genetic factors. CONCLUSIONS: While neither genes nor familial environment is likely to directly produce life events, personal and social factors that predispose to life events are substantially influenced by an individual's genetic and family background. These results, which suggest that stressful life events reflect more than random influences, may have important implications for our understanding of the relationship between stressful life events and psychopathology. PMID- 8215804 TI - Selective abnormalities of prefrontal serotonergic receptors in schizophrenia. A postmortem study. AB - BACKGROUND: This study investigates serotonergic receptors in prefrontal cortex of patients with schizophrenia. METHODS: We measured serotonin 2 receptors and serotonin uptake sites in prefrontal and occipital cortex of schizophrenics, patients with chronic schizoaffective disorders, nonpsychotic suicides, and controls. Diagnoses were established according to DSM-III-R criteria from medical chart reviews. RESULTS: In prefrontal cortex, serotonin 2 density was decreased in chronic psychotics dying of natural causes, as opposed to psychotics dying of suicide, controls, and nonpsychotic suicide victims. Serotonin uptake sites were decreased in prefrontal cortex of schizophrenics and nonpsychotic suicides, but not in patients with schizoaffective disorder. None of the observed differences were clearly related to antemortem pharmacological treatments. In the occipital pole, no differences were found among the groups. CONCLUSIONS: Selective prefrontal alterations of both presynaptic and postsynaptic serotonin receptor densities are present in at least some schizophrenic patients. PMID- 8215805 TI - An international study of psychological problems in primary care. Preliminary report from the World Health Organization Collaborative Project on 'Psychological Problems in General Health Care'. AB - This article describes a large longitudinal multicenter collaborative study that investigated the form, frequency, course, and outcome of psychological problems that were seen in primary health care settings in 15 different sites around the world. The research employed a two-stage sampling design in which the 12-item General Health Questionnaire was administered to 26,422 persons aged 18 to 65 years who were consulting health care services. Of these persons, 5604 were selected for detailed examinations using standardized instruments and were followed up at 3 months and 1 year to provide information on course and outcome. All assessment instruments have been translated into 13 different languages. The project has produced a database that allows for the exploration of the nature of psychological disorders experienced by patients in general medical care and their association with physical illness, illness behavior, and disability over time. PMID- 8215806 TI - Strong inference, theory testing, and the neuroanatomy of schizophrenia. AB - Failure to address the putative etiologic and pathophysiologic heterogeneity of the schizophrenia syndrome and problems in definitive assessment of human brain function have impaired progress in schizophrenia research. New approaches to psychopathology and converging evidence from antemortem and postmortem study can now result in more decisive study of the neuroanatomy and neuropathology of schizophrenia. PMID- 8215807 TI - The adrenal gland and depression. PMID- 8215808 TI - Adrenal gland enlargement in major depression. PMID- 8215809 TI - Muscarinic effects of clozapine and negative symptoms. PMID- 8215810 TI - A longitudinal twin study of 1-year prevalence of major depression in women. AB - OBJECTIVES: This study seeks to clarify the etiologic importance and temporal stability of the genetic and environmental risk factors for 1-year prevalence of major depression (1YP-MD) in women. DESIGN: One-year prevalence of major depression was personally assessed, using DSM-III-R criteria, at two time points a minimum of 1 year apart. PARTICIPANTS: Both members of 938 adult female-female twin pairs ascertained from the population-based Virginia Twin Registry. RESULTS: The correlation in liability to 1YP-MD was much greater in monozygotic (MZ) than in dizygotic (DZ) twins at time 1 alone, time 2 alone, or at either time 1 or time 2. Model fitting suggested that the liability to 1YP-MD was due to additive genes and individual specific environment with a heritability of 41% to 46% and was not biased by violations of the equal environment assumption. Jointly analyzing both times of assessment using a longitudinal twin model suggested that, over a 1-year period, genetic effects on the liability to 1YP-MD were entirely stable, while environmental effects were entirely occasion specific. CONCLUSIONS: These results suggest that: (1) genetic factors play a moderate etiologic role in the 1YP-MD, (2) the temporal stability of the liability to major depression in adult women is largely or entirely genetic in origin, and (3) environmental factors play a significant role in the etiology of major depression, but their effects are generally transitory and do not result in enduring changes in the liability to illness. PMID- 8215811 TI - A longitudinal twin study of personality and major depression in women. AB - OBJECTIVE: To elucidate the nature of the etiologic relationship between personality and major depression in women. DESIGN: A longitudinal twin design in which twins completed a time 1 questionnaire and, 15 months later, were personally interviewed for the occurrence of major depression during the last year and completed a time 2-questionnaire. Both questionnaires contained short forms assessing neuroticism and extraversion. PARTICIPANTS: 1733 twins from female-female pairs ascertained from the population-based Virginia Twin Registry. RESULTS: Extraversion was unrelated to lifetime or 1-year prevalence of major depression. Neuroticism was strongly related to lifetime prevalence of major depression and robustly predicted the prospective 1-year prevalence of major depression in those who, at time 1, denied previous depressive episodes. However, controlling for levels of neuroticism at time 1, levels of neuroticism at time 2 were moderately elevated in those who had had an episode of major depression between times 1 and 2 ("scar" effect) and substantially elevated in those experiencing an episode of major depression at time 2 ("state" effect). In those who developed major depression, levels of neuroticism did not predict time to onset. In the best-fit longitudinal twin model, the proportion of the observed correlation between neuroticism and the liability to major depression that is due to shared genetic risk factors was estimated at around 70%, that due to shared environmental risk factors at around 20%, and that due to a direct causal effect of major depression on neuroticism (via both "scar" and "state" effects) at around 10%. Approximately 55% of the genetic liability of major depression appeared to be shared with neuroticism, while 45% was unique to major depression. CONCLUSION: In women, the relationship between neuroticism and the liability to major depression is substantial and largely the result of genetic factors that predispose to both neuroticism and major depression. PMID- 8215812 TI - The lifetime history of major depression in women. Reliability of diagnosis and heritability. AB - BACKGROUND: In epidemiologic samples, the assessment of lifetime history (LTH) of major depression (MD) is not highly reliable. In female twins, we previously found that LTH of MD, as assessed at a single personal interview, was moderately heritable (approximately 40%). In that analysis, errors of measurement could not be discriminated from true environmental effects. METHODS: In 1721 female twins from a population-based register, including both members of 742 pairs, LTH of MD, covering approximately the same time period, was obtained twice, once by self administered questionnaire and once at personal interview. RESULTS: Reliability of LTH of MD was modest (kappa = +.34, tetrachoric r = +.56) and was predicted by the number of depressive symptoms, treatment seeking, number of episodes, and degree of impairment. Deriving an "index of caseness" from these predictors, the estimated heritability of LTH of MD was greater for more restrictive definitions. Incorporating error of measurement into a structural equation model including both occasions of measurement, the estimated heritability of the liability to LTH of MD increased substantially (approximately 70%). More than half of what was considered environmental effects when LTH of MD was analyzed on the basis of one assessment appeared, when two assessments were used, to reflect measurement error. CONCLUSIONS: Major depression, as assessed over the lifetime, may be a rather highly heritable disorder of moderate reliability rather than a moderately heritable disorder of high reliability. PMID- 8215813 TI - Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study. AB - BACKGROUND: It is widely acknowledged that the genetic diatheses for schizophrenia and affective disorders are independent. However, there are increasing doubts about this classic view, and empirical evidence for a dichotomy of these two prototypes of functional psychoses is limited. A controlled family study of consecutive admissions was conducted to determine whether familial risks for schizophrenic (SCZ) and affective disorders were independent or overlapping. METHODS: Index probands met Research Diagnostic Criteria for SCZ (n = 146), schizoaffective (SA [n = 115]), bipolar (BP [n = 80]), or unipolar major depressive (UP [n = 184]) disorder. Comparison probands met Research Diagnostic Criteria for alcoholism (n = 64) or were sampled from the general population (n = 109). A total of 2845 first-degree relatives were blindly diagnosed from interview, informant, and/or record data, with direct interviews completed in 2070 (82% of living first-degree relatives). RESULTS: By Cox's proportional hazards analysis, SCZ, SA, BP, and UP disorders were familial, in that each group of relatives had an increased lifetime morbid risk (vs those with alcoholism and those from the general population) for the proband's diagnosis. The SCZ and BP disorders were transmitted independently: only probands with manic disorders (BP or SA-BP subtype) showed increased familial risks of BP disorder, and only probands with prominent SCZ features (SCZ or SA) showed increased familial risks of SCZ disorder. However, SCZ probands had an increased familial risk for UP disorder (as did SA, BP, and UP probands) and for the SA-UP subtype. Aggregation of depression in families of SCZ probands could not be explained by the subtype of depression, broad or narrow definition of SCZ disorder, presence or absence of history of depression in SCZ probands, whether onset of depression in a relative occurred before or after onset of a proband's SCZ disorder, or assortative mating. CONCLUSIONS: These data suggest that there could be a familial relationship between the predispositions to schizophrenia and to major depression. We discuss a number of alternative hypotheses about the nature of this possible relationship. PMID- 8215814 TI - Antidepressants for the treatment of generalized anxiety disorder. A placebo controlled comparison of imipramine, trazodone, and diazepam. AB - OBJECTIVE: The current study examines whether antidepressants, contrary to current thinking, are safe and effective treatments for generalized anxiety disorder (GAD) not complicated by depression or panic disorder. DESIGN: Randomized, double-blind, placebo-controlled, flexible-dose, 8-week treatment study comparing imipramine hydrochloride (mean maximum daily dose, 143 mg), trazodone hydrochloride (255 mg), and diazepam (26 mg). PATIENTS: Two hundred thirty patients with a DSM-III diagnosis of GAD in whom major depression and panic disorder has been excluded, and who had a Hamilton Anxiety Scale total score of at least 18. SETTING: Seventy-five percent of patients were treated in family practice settings in the community, with the remainder treated in psychiatric practices, either academic or private. RESULTS: Patients treated with diazepam showed the most improvement in anxiety ratings during the first 2 weeks of treatment, with somatic symptoms being most responsive. From week 3 through week 8 trazodone achieved comparable, and imipramine somewhat better, anxiolytic efficacy when compared with diazepam, with psychic symptoms of tension, apprehension, and worry being more responsive to the antidepressants. Among completers, moderate to marked improvement was reported by 73% of patients treated with imipramine, 69% of patients treated with trazodone, 66% of patients treated with diazepam, but only 47% of patients treated with placebo. Overall, patients treated with antidepressants reported a higher rate of adverse effects than diazepam-treated patients, but attention rates were the same across all treatments. CONCLUSIONS: The results of the study need replication, but suggest a potentially important role for antidepressants, particularly imipramine, in patients suffering from GAD. PMID- 8215815 TI - Sex differences in rank attainment and research activities among academic psychiatrists. AB - Data from a survey distributed to all full-time faculty in academic departments of psychiatry were used to examine possible sex differences in research activities and rank attainment among psychiatrists. A total of 1923 psychiatrists responded, 1564 men (81.3%) and 359 women (18.7%). Continuous dependent variables were analyzed by using analyses of covariance with the year graduated from medical school as a covariate. For categorical dependent variables, the sample was divided into four 10-year cohorts based on the year graduated from medical school, and differences between men and women were analyzed with chi 2 tests. Over the entire sample, men were more likely than women to have had research training, to have ever been principal investigators on peer-reviewed grants, to mentor research trainees, to be currently involved in research activities, and to meet defined criteria as a "researcher." Many gender differences remained significant after controlling for seniority and research training. In every cohort, the men had attained higher academic rank than the women. In general, differences in research activity and productivity were most marked in the youngest cohort. To ensure a rich talent pool for psychiatric research, efforts must be made to recruit and support researchers from among the increased number of women in psychiatry. PMID- 8215816 TI - Twin studies of psychiatric illness. Current status and future directions. PMID- 8215817 TI - Diagnostic validity in genetics research on generalized anxiety disorder. PMID- 8215818 TI - Criminality associated with mental disorders and intellectual deficiency. PMID- 8215819 TI - Nucleolar organizer regions as discriminators for the diagnosis of well differentiated adenocarcinoma of the prostate. AB - This study sought to determine whether nucleolar organizer region (NOR) counts might be of diagnostic use specifically in the frequently difficult identification of well-differentiated prostate cancer. Total silver-stained NOR (AgNOR) counts on sections were done in 50 consecutive nuclei from 22 cases of well-differentiated adenocarcinoma composed exclusively of Gleason grades 1 or 2 and in 50 consecutive nuclei in foci of benign glands on the same slide. Malignant nuclei contained a mean of 4.84 AgNORs; benign nuclei, 3.39 AgNORs. This difference was statistically highly significant (P < .0001), but there was considerable overlap of mean AgNOR counts between malignant and benign groups. Thus, to obtain a rule requiring a specificity of greater than 95% using the mean AgNOR count as a definition of malignancy, the maximum sensitivity possible was only 32%. Despite the overlap in mean AgNOR counts, however, in all but one case the mean count for malignant nuclei was greater than that for benign nuclei. This suggests that the diagnostic potential of AgNOR counts might be better realized by a comparison of counts between a suspicious focus and an adjacent focus of benign glands. PMID- 8215820 TI - Medullary carcinoma of the breast. A multicenter study of its diagnostic consistency. AB - Nine pathologists from different institutions reviewed in a double-blind study 16 breast tumors previously indexed as typical medullary carcinoma, atypical medullary carcinoma, or infiltrative ductal carcinoma. A set of 16 slides was circulated two times among the nine pathologists. The diagnoses of typical and atypical medullary carcinomas were based on a definition given by Ridolfi et al. The interobserver and intraobserver agreement was low, with a kappa value of less than .50. The only histological criterion that had more than 50% agreement was the presence or absence of an in situ component in the tumor, assuming that the disagreement of one pathologist is accepted. This study is a snapshot of the problems encountered in the diagnosis of typical medullary carcinoma in a routine context and it shows high levels of variations in diagnostic consistency. PMID- 8215821 TI - Oat cell carcinoma of the gallbladder. A rare and highly lethal neoplasm. AB - Oat cell carcinomas arising in the gallbladder are an extremely rare and aggressive form of gallbladder cancer. These neoplasms are morphologically identical to their pulmonary counterparts, contain neurosecretory granules on ultramicroscopic examination, and demonstrate immunohistochemical staining for cytokeratin, neuron-specific enolase, and other neuroendocrine markers. Oat cell carcinomas typically occur in elderly women with cholelithiasis, and pursue a fulminant course with extensive metastases, especially to the liver. The mean survival is less than 7 months. We present a well-documented case of oat cell carcinoma of the gallbladder and review the literature on this unusual entity. PMID- 8215822 TI - Pancreatic fibrosis in patients with alcoholic dependence syndrome. AB - Pancreatic fibrosis in patients with alcoholic dependence syndrome was studied histopathologically. In 30 of 41 autopsied patients with alcoholic dependence syndrome, fibrosis was observed despite the absence of clinical pancreatitis. The fibrosis was categorized into three types, according to Martin's classification: intralobular sclerosis in 15 cases, perilobular sclerosis in seven cases, and a mixed intralobular and perilobular sclerosis in the remaining eight cases. The type of the fibrosis was not related to the duration of alcohol abuse. Alcoholic liver cirrhosis was coexistent in 23 of the 30 cases of pancreatic fibrosis. These cases were also divided into categories according to the three types, as follows: intralobular sclerosis in 12 (80%) of 15 cases, perilobular sclerosis in four (57%) of seven cases, and mixed sclerosis in seven (88%) of eight cases. That is, intralobular and mixed sclerosis were frequently coexistent with alcoholic liver cirrhosis. When the pancreases from the 19 subjects with intralobular sclerosis and mixed sclerosis coexistent with liver cirrhosis in alcoholic dependence syndrome were compared with 20 pancreases from patients with nonalcoholic liver cirrhosis, periacinar (or intralobular) fibrosis was found in all cases of the former, but in none of the latter. Hence, it was concluded that periacinar fibrosis occurred as a result of alcohol abuse. Pancreatic fibrosis in patients with alcoholic dependence syndrome was distributed mainly in the intralobular areas and was frequently coexistent with alcoholic liver cirrhosis. PMID- 8215823 TI - Hyaline splenic and hepatic plaques. Correlation with cirrhosis, pulmonary tuberculosis, and asbestos exposure. AB - Nine hundred twenty-five unselected autopsies were investigated for the presence or absence of hyaline peritoneal (splenic or hepatic) plaques, hyaline pleural plaques, asbestos, liver cirrhosis, heart failure, previous peritoneal dialysis or abdominal surgery, chronic peritonitis, splenomegaly, splenic infarcts, and pulmonary or abdominal tuberculosis. Lung asbestos body concentrations were calculated in 570 subjects. Peritoneal plaques were recorded in 163 cases. In both univariate and multivariate analyses, they were associated with cirrhosis, pulmonary nonactive tuberculosis, pleural plaques, and asbestosis. Association with asbestos body counts was also found, with a significant trend. Peritoneal plaques were described long ago in different pathologic conditions, for some of which (cirrhosis and nonactive pulmonary tuberculosis) the association is confirmed by the present analysis. It is suggested that they are significantly associated, moreover, with indicators of asbestos exposure. PMID- 8215824 TI - Spontaneous abortions during the second trimester of gestation. AB - To determine the factors causing spontaneous abortions, 422 consecutive second trimester abortions and the corresponding clinical data were studied prospectively. All of the fetuses and placentas were referred to a single pathologist and microbiological cultures were carried out in 205 of these cases. One hundred twenty-one medically included abortions were used as controls for the interpretation of the investigations relating to infection. According to the degree of maceration, two groups could be isolated and seemed to represent different diseases and mechanisms of spontaneous abortions. In the largest group (78.6%) without long intrauterine retention, one explanation could be given for 85% of these cases. Ascending infections occurred through unruptured membranes, whether or not they were associated with obstetric complications. The second group (21.4%) included severely macerated fetuses where a cause of death could only be determined in 44% of the cases that had a predominance of fetal abnormalities and maternal factors. PMID- 8215825 TI - Tumors of the heart. A 20-year experience with a review of 12,485 consecutive autopsies. AB - Cardiac involvement by primary and secondary tumors is one of the least investigated subjects in oncology. Seven cases of primary and 154 cases of secondary cardiac tumors from autopsies performed over a 20-year period (1972 through 1991) at Queen Mary Hospital, Hong Kong, were reviewed. During this period, 12,485 autopsies were performed, and the autopsy incidence for primary and secondary heart tumors is thus 0.056% and 1.23%, respectively. Only seven primary cardiac tumors were found, including two myxomas, two rhabdomyomas, two hemangiomas, and one lipoma. For secondary tumors involving the heart (including both metastasis and local extension), important primary tumors in male subjects were carcinoma of the lung (31.7%), esophageal carcinoma (28.7%), lymphoma (11.9%), carcinoma of the liver (6.9%), leukemia (4.0%), and gastric carcinoma (4.0%), while in female subjects, carcinoma of the lung (35.9%), lymphoma (17.0%), carcinoma of the breast (7.5%), and pancreatic carcinoma (7.5%) predominated. Overall, the three most common malignant neoplasms encountered were carcinoma of the lung, esophageal carcinoma, and lymphoma. Pericardium, including epicardium, was the most common location of cardiac involvement by secondary tumors, followed by myocardium and endocardium. The present study showed a higher percentage of esophageal carcinoma and carcinoma of the liver (reflecting the higher incidence of these tumors in Hong Kong Chinese), but a lower incidence of carcinoma of the breast when compared with other series. The metastatic lung tumors showed an unusual predominance of adenocarcinoma. PMID- 8215826 TI - Chronic intervillositis of the placenta. AB - We report six cases of chronic intervillositis, an infrequently recognized placental lesion that is characterized by a prominent mononuclear inflammatory cell infiltrate in the intervillous space and that is associated with poor fetal outcome. In all six placentas, the inflammatory infiltrate was essentially limited to the intervillous space: chronic villitis was present focally only in one and absent in the other five. Additional placental histopathologic findings included increased villous fibrinoid material in all six, infarcts in two, atherosis in decidual vessels in two, and acute chorioamnionitis in two. Results of immunohistochemical staining confirmed the predominantly histiocytic nature of the intervillous infiltrate. Two mothers had a history of severe preeclampsia, one had elevated blood pressure at the time of delivery, two had a history of substance abuse, two had a history of systemic lupus erythematosus treated with prednisone, and one of these last two also had diabetes. Five of the six pregnancies resulted in perinatal death. One fetus was nonviable, one was anencephalic, one died in utero, and two died of complications of prematurity shortly after birth; one of the premature infants was small for gestational age. The mononuclear nature of the inflammatory cell infiltrate and its association with increased villous fibrinoid material and atherosis suggests an immunological origin, although the possibility that this lesion may have an infectious cause cannot be excluded. PMID- 8215827 TI - Hepatobiliary cystadenoma. A study of five cases with reference to histogenesis. AB - Hepatobiliary cystadenoma is a rare hepatic lesion characterized by a multiloculated cyst lined by cuboidal or columnar epithelial cells. Four cases of hepatobiliary cystadenoma with mesenchymal stroma (HCMS) and one case of hepatobiliary cystadenoma with intracystic epithelial component were studied by light microscopy, immunohistochemical methods, and electron microscopy. Similar studies were conducted on six fetal gallbladder tissues, representing the biliary tree, and two adult ovarian tissues. By light microscopy, the columnar epithelium of the five cases of hepatobiliary cystadenoma was similar to the epithelium of the developing gallbladder. The spindle cell stroma of the HCMS and the subepithelial spindle cells of the developing gallbladders showed similar reactivity to smooth-muscle actin. Vimentin reactivity was strongly positive in the stroma of the HCMS, and in the fetal gallbladders it was only noted in the subepithelial spindle cells of the 15-week gestation fetal gallbladder tissues. By electron microscopy, the epithelium lining the hepatic lesions showed characteristic gastrointestinal features and was identical to the epithelia lining the embryonic gallbladders. Furthermore, the mesenchymal stroma of the HCMS recapitulated the features found in subepithelial tissues in developing gallbladders. Although the ovarian stroma resembled the stroma of the HCMS by light microscopy, the immunohistochemical reactions and the electron microscopic studies showed dissimilarities. This study supports the hypothesis that the hepatobiliary cystadenomas arise from ectopic embryonic tissues destined to form the adult gallbladder. PMID- 8215828 TI - Acanthamoeba infection presenting as skin lesions in patients with the acquired immunodeficiency syndrome. AB - Acanthamoeba organisms are a well-known, although rare, cause of central nervous system infection in immunodeficient hosts, including those with the acquired immunodeficiency syndrome. Extracerebral acanthamebiasis, with the exception of contact lens-associated keratitis, is reported but little emphasized in the literature. We describe two patients with the acquired immunodeficiency syndrome in whom skin lesions were the primary manifestations of Acanthamoeba infection. Central nervous system disease was proved in one patient and suspected, but unproved, in the other. The skin lesions exhibited an intact epidermis with suppurative inflammation of the subcutis, associated with numerous amebic cysts and trophozoites. The amebic cyst walls stained with periodic acid-Schiff and Gomori's methenamine-silver stains, creating confusion with Blastomyces dermatitidis yeast in one instance. Immunofluorescence studies and culture identified the organisms as an Acanthamoeba species. Preliminary studies in one of the cases suggested a previously undescribed Acanthamoeba species as the etiologic agent. Our experience emphasizes that skin lesions may be the presenting sign of disseminated Acanthamoeba infection in patients with the acquired immunodeficiency syndrome. PMID- 8215829 TI - Fine-needle aspiration anchor. A simple device to prevent needle-stick injury at fine-needle aspiration. AB - Pathologists and clinicians performing fine-needle aspiration for cytologic diagnosis are at risk of finger injury by the needle during the aspiration procedure. To prevent this occurrence and its accompanying potential for transmitting serious pathogens such as the human immunodeficiency virus and hepatitis B virus, we have designed a simple acrylic device (fine-needle aspiration anchor) consisting of two curved prongs with an attached handle, to take up the functions of the fingers for stabilization of the target lesion. Use of the fine-needle aspiration anchor on more than 1000 patients with various mass lesions has confirmed enhanced immobilization of the lesions for aspiration, safety for the person performing the procedure, and excellent patient acceptance. PMID- 8215830 TI - Histologic, ultrastructural, and immunocytochemical features of the granulomas seen in a child with the syndrome of familial granulomatous arthritis, uveitis, and rash. AB - A family with a syndrome consisting of granulomatous arthritis, uveitis, and rash was first described in 1985. Another family with the same syndrome was described subsequently in 1990. The condition, in both families, is clinically different from sarcoidosis. To verify whether the granulomas in such patients also could be distinctive, we performed histologic, ultrastructural, and immunocytochemical studies on skin and synovial biopsy specimens from a child under our care who suffered from the same syndrome. The results indicated that the granulomas could not be distinguished from those seen in sarcoidosis either by light microscopy or by immunocytochemical studies. However, by electron microscopy, "wormlike" or "comma-shaped" bodies were noted within the cytoplasm of epithelioid cells. The significance of this observation is discussed. PMID- 8215831 TI - Actin-positive spindle cell lymphoma. AB - We report an unusual case of malignant lymphoma, large noncleaved B-cell type, exhibiting sarcomatoid and myxoid patterns and strong positive staining for muscle-specific actin. Despite vigorous chemotherapy, the 64-year-old male patient, who had lymphoma involving his right inguinal area, retroperitoneum, and anterior chest wall at the time of presentation, died 3 months later. PMID- 8215832 TI - Microtubule aggregates in a clival chordoma. AB - We report a case of a clival chordoma in a 21-year-old man that ultrastructurally demonstrated large numbers of microtubule aggregates within the rough endoplasmic reticulum. Histologically, the tumor demonstrated classic chordoma architecture characterized by numerous physaliphorous cells and an abundant extracellular matrix. The tumor cells stained strongly for cytokeratin, S100 protein, and epithelial membrane antigen, indicative of the epithelial origin of this tumor. Ultrastructurally, the most conspicuous feature of this tumor consisted of parallel bundles of criss-crossing microtubules within the rough endoplasmic reticulum. These microtubules had a diameter of approximately 27 nm and did not demonstrate an internal structure. To our knowledge, this is the first report of microtubule aggregates in a spheno-occipital chordoma. We note that microtubule aggregates have been described in a number of different entities, and though proposed as a specific feature of "chondroid chordoma," they are a nonspecific finding. PMID- 8215833 TI - Correlation of hemoglobin H inclusion bodies with genotype in alpha-thalassemia. PMID- 8215834 TI - Iron, hematocrit, and the sex difference in heart disease. PMID- 8215835 TI - Mucin-positive epithelial mesothelioma and pseudomesotheliomatous adenocarcinoma. PMID- 8215836 TI - Pseudoparasites due to ciliocytophthoria. PMID- 8215837 TI - Clinicopathologic significance of p53 immunostaining in adenocarcinoma of the breast. AB - Methanol/acetone-fixed frozen sections of 87 breast carcinomas were studied with a panel of three anti-p53 monoclonal antibodies that had specificities for wild type, mutant, or combined wild-type plus mutant epitopes by using the avidin biotin method. Nuclear staining was present in 13 (15%) of 87 cases with the mutant-specific antibody. The combined-specificity antibody stained 28 (32%) of 87 cases, including all but one of the tumors that was positive with the mutant specific antibody. None of the cases reacted with the wild-type-specific antibody. Immunostaining for mutant form p53 was strongly correlated with adverse clinicopathologic factors, including poor differentiation, absence of estrogen receptor protein, nodal metastases, and large tumor size. In groups that were stratified by axillary node status, disease-free survival (52-month mean follow up) was worse among cases with positive staining for either antibody. This difference was statistically significant in node-positive patients with the combined-specificity antibody (disease free, 22% [p53+] vs recurred, 57% [p53+]). We concluded that (1) immunostaining for mutant forms of p53 characterizes a clinically aggressive subset of breast tumors and may have prognostic utility in some patient populations, and (2) antibody-dependent-staining patterns for p53 may reflect epitope specificities of various mutant forms. PMID- 8215838 TI - The application of a rapid D-dimer test in suspected pulmonary embolus. AB - A prospective, consecutive series of plasma D-dimer (D-D) using a rapid, sensitive, and semiquantitative latex agglutination test from 169 patients clinically suspected of having acute pulmonary embolus (PE) was performed to determine its clinical utility in acute PE. All patients had ventilation/perfusion (V/Q) scans and 20 patients (12%) subsequently had pulmonary arteriography (PAG). The 20 patients who subsequently had PAG were used to establish the predictive value(s). In 10 patients with normal D-D results, none had PE according to PAG. In 10 patients with abnormal D-D results, seven showed PE by PAG and three did not show PE by PAG. The sensitivity, specificity, positive predictive values, and negative predictive values of the plasma D-D tests for acute PE based on PAG were 1.00, 0.77, 0.70, and 1.00, respectively. In nine patients with indeterminate V/Q scans who had PAG, four had PE and the D-D result was abnormal. Five of these patients did not have PE and the D-D result was abnormal in three and normal in two. Seventeen patients had high-probability V/Q scans, all of whom had abnormal D-D results. Only one had PAG that showed PE in this group. A normal D-D result using a rapid latex agglutination method can effectively exclude the diagnosis of acute PE. The negative predictive value of the rapid latex agglutination method is as good as the more cumbersome enzyme linked immunosorbent assay methods. An abnormal result is nonspecific and is not useful in the diagnosis of acute PE. While some "false positives" did occur, there were no false-negative results. The best use of the D-D test is in the examination of the patient with indeterminate V/Q studies. We conclude that the D D test can rapidly provide information in determining whether a patient needs further angiographic studies. PMID- 8215839 TI - Chronic idiopathic thrombocytopenic purpura. Splenic pathologic features and their clinical correlation. AB - We studied 83 patients who had chronic idiopathic thrombocytopenic purpura refractory to steroid therapy and who underwent splenectomy. The positive rates of antiplatelet and antinuclear antibodies were 40% (30/75 patients tested) and 41% (25/61 patients tested), respectively. The morphologic characteristics of splenic pathologic findings included prominent secondary follicles and foamy macrophages, present in 23 (28%) and 56 (67%) of patients, respectively. Extramedullary hematopoiesis was noted in 50 (60%) of the patients. Eight patients (10%) presented with periarterial fibrosis, and three of them had systemic lupus erythematosus. The 23 patients (28%) with prominent secondary follicles were younger than the other patients, were preponderantly female, and had a higher rate of antiplatelet antibody production, and all had an initial response with a greater increase in platelets postoperatively. Eight patients (10%) had neither prominent secondary follicles nor foamy macrophages and lower splenic weights; their initial response compared with that of other patients was significantly poorer. The thrombocytopenia in these patients might have a different mechanism. PMID- 8215840 TI - Diagnostic utility of postmortem blood cultures. AB - The autopsy is receiving renewed emphasis as a tool for quality assurance in clinical medicine. Postmortem blood cultures frequently are taken during the autopsy but are costly and of unclear diagnostic utility. To assess whether postmortem blood cultures contribute any useful information not already known from antemortem blood cultures, we compared positive postmortem blood cultures taken in 111 autopsies with the results of antemortem blood cultures. Of these, 60 (54%) of 111 had positive postmortem blood cultures despite a cause of death not related to an infectious cause. Of the 111 patients, 54 (49%) had antemortem blood cultures drawn in the 7 days before death, of which 34 (63%) of 54 were negative and 20 (37%) of 54 were positive. Of the 20 patients with true antemortem bacteremia/fungemia, seven (35%) had postmortem blood cultures that yielded the same organism, 10 (50%) yielded multiple organisms that were considered to be contaminants, and three (15%) yielded different organisms. These latter three cultures yielded microorganisms that were related to the patients' illness but did not provide additional information not already known from antemortem blood cultures or the patients' clinical or autopsy findings. Of the 91 patients who had no, negative, or contaminated antemortem blood cultures, 69 (76%) had postmortem blood cultures that yielded contaminants and 22 (24%) yielded microorganisms that were indeterminate as a cause of sepsis and, therefore, did not yield new or useful information. In summary, results of postmortem blood cultures rarely, if ever, provide information that is not already known, can be interpreted, provide new insights into pathophysiology, or detect errors in therapy. PMID- 8215841 TI - Type IV Ehlers-Danlos syndrome with aspirin sensitivity. A family study. AB - The purpose of this study was to investigate a family with type IV Ehlers-Danlos syndrome (EDS-IV) and platelet sensitivity to aspirin, an association that, to our knowledge, has not been reported previously. Type IV Ehlers-Danlos syndrome is a rare disorder of type III collagen metabolism characterized by bruising easily and death at an early age from exsanguination by rupture of a major viscus or artery. Previous studies have suggested an association between various types of Ehlers-Danlos syndrome and abnormal platelet function. In this family, EDS-IV is inherited in an autosomal dominant pattern. The transmission of the platelet functional disorder from the proband to only one of two children affected with EDS-IV in this family suggests that there is a genetic component to this condition that is independent of EDS-IV. PMID- 8215842 TI - Synthesis and antitumor activity of some new 2-chloroethylnitrosoureas. AB - The synthesis of a series of N-(2-chloroethyl)-N'-(9H-xanthen-9-yl)-N nitrosoureas and N-(2-chloroethyl)-N'-(9H-thioxanthen-9-yl)-N-nitrosoureas is described. The title compounds were evaluated against NSCLCN6 L16 bronchial epidermoid carcinoma in vitro and some of them were found to be active. N-(2 chloroethyl)-N'-(2-methoxy-9H-xanthen-9-yl)-N-nitrosourea (8e) was active against leukemia P388 tumor system in mice. PMID- 8215843 TI - Synthesis and chemotactic activity of the fMLP analog HCO-Hmb-Leu-Phe-OMe. AB - The new fMLP analog HCO-Hmb-Leu-Phe-OMe (1), containing (S)-2-hydroxy-4 (methylthio)butyric acid (Hmb) in place of L-methionine at the N-terminal position, has been synthesized and fully characterized. The peptide 1 has been designed in order to improve the understanding of the role exerted by the formamido group in the binding interaction with the formylpeptide chemotactic receptors. Chemotaxis, superoxide anion production, and lysozyme release have been measured for both 1 and its deformylated analog Hmb-Leu-Phe-OMe 2. Results indicate that a strong hydrogen bond of the OH....O = C type may complement a weak H-bonding interaction involving the formylic proton as H-bond donor. PMID- 8215844 TI - Hypolipidemic activity and toxicity of 3-methoxy-N,N'-diaminophthalamide in rodents. AB - 3-Methoxy-N,N'-diaminophthalamide was observed to be a potent hypolipidemic agent in rodents. Serum cholesterol and triglyceride levels in rats were significantly reduced as were lipid contents of the liver, small intestine, and aorta wall. VLDL and LDL cholesterol levels were significantly reduced. Unfortunately, HDL cholesterol levels were also markedly reduced. Furthermore, acute toxicity studies showed that the compound caused marked increases in serum CP kinase activity with doses of 40 and 100 mg/kg/day in mice. This is not a property of the 2,3-dihydrophthalazine-1,4-dione, the resultant product of the N,N' diaminophthalamides. Apparently, closing the ring results in a safer compound with elevations in HDL cholesterol levels, a desirable characteristic in effective hypolipidemic agents. PMID- 8215845 TI - [Antimycotic agents. 20. Bioisoteric 6-arylpyrimidine derivatives]. AB - Condensation of N-(2-hydroxyethyl)-N-methylguanidine-sulfate (1) with the beta diketones 4a-e bearing 1-aryl substituents leads to the bioisosteric 2-[(2 hydroxyethyl)-methylamino]-6-arylpyrimidines 5a-e. Compounds 5a-c exhibit significant antimycotic in vivo and in vitro activities. PMID- 8215846 TI - Phenytoin-lipid conjugates as potential prodrugs of phenytoin. AB - Phenytoin-1-triglycerides and phenytoin-2-triglycerides were synthesized as potential prodrugs of phenytoin by covalent binding of 3-hydroxymethylphenytoin by succinic acid to the positions 1 and 2 of diglycerides, respectively. The corresponding 1- and 2-monoglycerides were prepared. In addition, replacement of glycerol by 3-hydroxy-2-hydroxymethylpropionic acid furnished lipids that allowed direct coupling of 3-hydroxymethylphenytoin. The lipid conjugates proved to be substrates for pancreatic lipase in vitro. PMID- 8215847 TI - New NO-donors with antithrombotic and vasodilating activities, I: 3-Arylalkyl-N nitroso-5-sydnone imines. AB - Nine nitrosimino title compounds were prepared. They inhibit the aggregation of human platelets induced by collagen with an IC50 = 0.7--33 mumol/L. The most active substance is the 3-phenylethyl derivative 6b. The in vitro effect is mediated by an active metabolite which is formed by a photochemical reaction in the aggregometer. As the corresponding and so far unknown sydnone-5-cyanimines have no effect on platelets the metabolite is most certainly a NO-species. The activity of the sydnone-5-nitrimine 5b is in the same order of magnitude (IC50 = 7.5 mumol/L) as in the nitrosimines of type 6. The most active compound 6b was investigated for antithrombotic properties in a thrombosis model, where the thrombus formation was induced by a laser-beam. 2 h after oral administration of 60 mg/kg of 6b to rats in venoles a 28% inhibition of thrombin formation was found. In arterioles this effect is more evident and a 48% inhibition is seen (the thrombus formation index is 2.6 and 3.9, respectively). These results suggest that the active metabolite is formed as well in vivo. PMID- 8215848 TI - Synthesis and antimicrobial evaluation of novel oxa(thia)diazolylquinolines and oxa(thia)diazepino[7,6-b] quinolines. AB - Three novel series of quinoline derivatives have been prepared by cyclization of the intermediate 3[(substituted)thiocarbamoyl-hydrazonomethyl]-2-chloroquinoline s and 3-aroylhydrazonomethyl-2-chloroquinolines: 3-(3-Acetyl-5-(substituted)-2,3 dihydro-1,3,4-oxa(thia)diazol-2-yl )-2- chloroquinolines (4; 5), 3-(5 (substituted)-1,3,4-oxa(thia)diazol-2-yl)-2-chloroquinolin es (6; 7), and 2 (substituted)-1,3,4-oxa(thia)diazepino[7,6-b]quinolines (8; 9). The antimicrobial activity of these compounds was studied. PMID- 8215849 TI - Transformational growth factor, a new application for an old hormone: a case study. PMID- 8215850 TI - The John Stanley Coulter Lecture. Health care reform and disability: affirming our commitment to community. PMID- 8215851 TI - Sexual activities, response and satisfaction in women pre- and post-spinal cord injury. AB - Twenty-five spinal cord injured (SCI) women (median age = 34) completed an 80 item multiple choice questionnaire (median 50 months postinjury) that assessed sexual functioning pre-spinal cord injury and post-spinal cord injury in four areas: (1) sexual adjustment; (2) sexual activities and preferences; (3) sexual desire, arousal and satisfaction; and (4) sexual abilities. Frequency of sexual activity decreased following SCI. Intercourse was the favorite activity preinjury; whereas, kissing, hugging and touching were favored postinjury. Sexual desire and satisfaction decreased postinjury. Ability to achieve lubrication and orgasm with various types of spinal injuries is reported. Although most women did not receive sexual information or counseling, 76% of the sample believed they had been adjusting well sexually. Results are discussed accounting for the limitations of self-report methodology in sexuality research. The need for laboratory based, physiologic studies is underscored. PMID- 8215852 TI - Long-term spinal cord injury: functional changes over time. AB - Functional changes were assessed in a group of 279 individuals with long-term spinal cord injuries. All had sustained their initial injuries 20 to 47 years ago and all had received initial and postinjury follow-up care at one of two British spinal cord injury treatment centers. Twenty-two percent reported that the need for physical assistance from others had increased over the years. Most (45%) needed additional help with transfers; others needed more assistance with dressing, mobility, and toileting. When compared to those whose need for help had not increased, significant differences were found by age: as a group, and when separated by level and severity of injury, those needing more help were older, and those with cervical injuries needed help at younger ages than their counterparts with lower level injuries. Those needing more help also had significantly more reports of shoulder pain, fatigue and weakness, weight gain, and postural changes. They used more attendant care, and perceived their quality of life to be lower than those whose level of function had not changed over time. PMID- 8215853 TI - Traumatic spinal cord injury in Arkansas, 1980 to 1989. AB - To develop and implement target prevention strategies, we studied the causes of spinal cord injuries in Arkansas and the groups most affected by SCI. Any Arkansas resident with a spinal cord injury who satisfied the state registry criteria was defined as a subject. Transportation-related incidents caused 319 (49.5%) of the SCIs. Males 15 to 24 years of age experienced the highest incidence of SCI because of transportation and sport-related injuries. The rate of SCI from falls was 2.8 times higher for people 65 years of age and older than for people 64 years of age and younger. Minority males 15 to 44 years of age were at the greatest risk of violence-related SCIs. More intervention is needed in the areas of transportation and sport-related causes involving males 15 to 24 years of age, fall-related causes involving the elderly, and violence-related causes involving minority males 15 to 44 years of age. PMID- 8215854 TI - Psychosocial recovery after head injury. AB - Psychosocial recovery after head injury was prospectively examined at 1 and 12 months postinjury in a group of 102 hospitalized adult head-injured patients representing a broad range of head injury severity. For comparison purposes, 102 friend controls were used. Outcome was assessed with a battery of psychosocial measures including the Sickness Impact Profile, the Head Injury Symptom Checklist, and the Modified Function Status Index. The results indicate that head injury patients experience significant psychosocial problems (eg, ability to return to work, resume leisure activity, concentrate and remember information, feelings of irritability) at both 1 and 12 months postinjury but these difficulties improve over time. Whereas improvements occur in both psychosocial and physical areas of functioning, improvements are greater in the physical area. The nature and extent of difficulties seen vary as a function of head injury severity, and time from injury to observation. Finally, the results suggest that not all problems reported by head-injured patients are solely related to the injury (eg, irritability, anxiety, fatigue, or headaches). PMID- 8215855 TI - Family functioning and injury severity as predictors of child functioning one year following traumatic brain injury. AB - This study examined changes in children's functioning in the year following traumatic brain injury (TBI) and the preinjury family and injury factors most predictive of children's overall adaptive functioning and social competence at 1 year. Ninety-four children with TBI (mild = 50, moderate = 25, severe = 19) and their families were consecutively enrolled from two regional medical centers. The age range was from 6 years to 15 years. Interviewer ratings and standard measures of family and child functioning were completed within 3 weeks of injury (measuring preinjury status), at 3 months and 1 year. Mean preinjury parent and teacher ratings of child functioning were within normal range. Older children (> or = 12 years) had worse preinjury functioning than younger children. Declines in child functioning were significantly associated with injury severity. Mild and moderately injured children had few declines in overall functioning. Severely injured children had the most dramatic early declines and improved only slightly between 3 months and 1 year; however, older children from poorly functioning families deteriorated in the same period. Injury severity and preinjury family functioning explained from 25% to 39% of the variation in child functioning at 1 year and up to 57% when the child's preinjury status was included. Children at risk for poorer adaptation following TBI can be identified and for optimal recovery should receive appropriate support services for optimal recovery. PMID- 8215856 TI - Prevalence and associated features of depression and psychological distress in polio survivors. AB - This cross-sectional study examines the prevalence of psychological distress and depression among 116 polio survivors. It investigates demographic, medical, and coping differences between subjects with (n = 17) and without (n = 99) these symptoms. Subjects were administered the Brief Symptom Inventory (BSI), the Coping with Disability Inventory (CDI), and a questionnaire about their polio histories. The BSI provided measures of psychological distress and depression that defined the subgroups. The CDI assessed coping behaviors. BSI scores for the overall sample were within the normal range indicating no major distress, depression, nor elevated somatic complaints. Several significant differences were found between the two subgroups. On average, depressed/distressed subjects reported an increase in pain (p < .01) and further deterioration of their medical status since the time of their physical best subsequent to the onset of polio (p < .01). They consistently rated their health as poorer than did nondepressed/nondistressed subjects (p < .001). They also reported less satisfaction with life and their occupational status (p < .001) and displayed poorer coping behaviors combined (p < .001). Selected variables such as life satisfaction, pain, decrease in activity, and current living situation accounted for 51% of the variance when predicting distress and depression among this group of polio survivors. PMID- 8215857 TI - The neuropsychology of post-polio fatigue. AB - To test the hypothesis that post-polio fatigue and its concomitant cognitive deficits are associated with an impairment of attention and not of higher-level cognitive processes, six carefully screened polio survivors were administered a battery of neuropsychological tests. Only subjects reporting severe fatigue, and not those with mild fatigue, demonstrated clinically significant deficits on all tests of attention, concentration, and information processing speed while showing no impairments of cognitive ability or verbal memory. These findings suggest that an impaired ability to maintain attention and rapidly process complex information appears to be a characteristic in polio survivors reporting severe fatigue, because these deficits were documented even when their subjective rating of fatigue was low. This finding supports the hypothesis that a polio-related impairment of selective attention underlies polio survivors' subjective experience of fatigue and cognitive problems. PMID- 8215858 TI - Effects of bolus volume, viscosity, and repeated swallows in nonstroke subjects and stroke patients. AB - This study examined the effects of bolus volume and viscosity and the variability of repeated swallows in ten stroke patients and ten age-matched nonstroke subjects. The ten stroke patients demonstrated single unilateral cortical (three subjects), subcortical (six subjects), or brainstem (one subject) infarcts on computed tomography or magnetic resonance imaging scans at three weeks post ictus. All subjects underwent videofluoroscopic swallow studies in which seven temporal pharyngeal swallow measures were examined. Despite the dissimilarity in lesion locations, the swallow physiology in the stroke patients was relatively homogeneous, ie, no swallowing disorders severe enough to prevent oral intake. As bolus volume increased, pharyngeal delay time diminished in stroke patients, but not in nonstroke subjects. Increasing bolus volume affected three other pharyngeal swallow measures similarly in nonstroke and stroke subjects: laryngeal closure durations and cricopharyngeal (CP) opening durations increased and duration of tongue base contact to posterior pharyngeal wall decreased. On viscosity comparisons (liquid vs paste), both subject groups displayed longer duration of base of tongue contact to posterior pharyngeal wall. On paste swallows, nonstroke subjects had longer CP opening and lower swallow efficiency, whereas stroke patients did not. This study found no statistically significant learning/repetition effect for repeated swallows in either subject group, or both groups combined. PMID- 8215859 TI - Cervical range of motion in the elderly. AB - This study was conducted to establish normative cervical range of motion values for the elderly and to compare those values to standard young adult cervical range of motion values. Differences in range of motion between men and women were also assessed. A gravity goniometer was used to measure six cervical motions in 42 subjects aged 70 to 90 years and 31 subjects aged 20 to 30 years. The elderly group had significantly less motion than the younger group for all six motions measured (p < .001). A comparison of the mean range of motion values between the two groups found that the elderly group had approximately 12% less flexion, 32% less extension, 22% less lateral flexion, and 25% less rotation. The elderly group also had a wider variation of cervical range of motion values as compared to the younger group. Women had greater cervical range of motion values than men in both age groups. PMID- 8215860 TI - Frequency and volume of resistance training: effect on cervical extension strength. AB - Quantification of cervical extension (CERV EXT) strength is complicated by the inability to stabilize the torso and isolate the CERV EXT muscles. A newly developed machine designed to stabilize the torso and isolate the CERV EXT muscles was used to evaluate the effect of frequency and volume of resistance training on CERV EXT strength. Fifty men (age, 26 +/- 9 years; height, 174 +/- 16 cm; weight, 74 +/- 9 kg) and 28 women (age, 30 +/- 9 years; height, 152 +/- 32 cm; weight, 62 +/- 7 kg) volunteered to participate. Subjects were randomly stratified to one of four training groups or a control group (CONT, n = 19) that did not train. Each training group exercised for 12 weeks as follows; once per week using one set of dynamic exercise (DYN 1x/wk, n = 14), once per week using one set of DYN and one set of maximal isometric (IM) exercise at eight angles through a 126 degrees-range of CERV EXT (DYN-IM 1x/wk, n = 16), DYN 2x/wk (n = 19), or DYN-IM 2x/wk (n = 10). Maximal IM torque was measured at eight angles initially and after 12 weeks of training. All training groups improved CERV EXT strength (p < or = 0.05) at all angles tested compared to the CONT except for DYN once per week at 0 degree of CERV flexion. A greater increase in strength was found when the groups that trained two times a week were compared to those that trained once per week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215861 TI - Short bed stays: their effect on occupational therapy services in teaching hospitals. AB - The purpose of this exploratory study was to determine the nature of Australian occupational therapy practice and the factors that make that practice successful in short stay, acute care hospitals. The study used a qualitative methodology in the form of focus group discussions. The primary finding of the study is the reconceptualization of the occupational therapy role, which has occurred as a result of the economic constraints imposed on the health care system that have necessitated shorter bed stays for patients. This role is characterized by an assess/discharge plan cycle rather than the more long-term, rehabilitation approach of assess/treat/discharge. This information is useful for practitioners, department managers, hospital administrators, and occupational therapy educators. PMID- 8215862 TI - Total knee arthroplasty: evaluation of an acute care rehabilitation program. AB - This retrospective research was performed to evaluate the acute care rehabilitation program provided for patients receiving total knee arthroplasties in one institution. Included were 146 patients with unilateral arthroplasties and 40 patients with bilateral arthroplasties. Care and charge data, functional scores, and discharge disposition were documented for all subjects. The mean hospital days and associated charges were, respectively, 9.9 and $16,149 for unilateral arthroplasties and 11.9 and $23,594 for bilateral arthroplasties. Significant improvements in function (bed mobility, transfers, locomotion, and stairs) occurred during the course of rehabilitation. Over 96% of the patients were discharged home (either with or without services). Predictive of both discharge disposition and hospital charges were arthroplasty type, initial bed mobility score, and discharge transfer score. The results demonstrate differences associated with unilateral and bilateral surgeries, verify that functional changes accompany rehabilitation, and show that functional capacity has implications for charges and discharge disposition. PMID- 8215863 TI - An analysis of sit-to-stand movements. AB - We analyzed the movements involved in rising from a knee-high chair in 12 healthy men weighing within +/- 10% of standard body weight. A regular series of transition points was observed in the angles of the hip, knee, and ankle joints throughout the sit-to-stand movement, which was classified into six stages. As the duration of sit-to-stand movements increased, the duration of Stage 2 decreased, whereas Stage 3 grew longer. The durations of stages 4 and 5 remained constant. We also calculated the minimum unilateral hip and knee extension torque per weight in kilograms required for natural sit-to-stand movements, or N-Stand (1.7-2.3 seconds), and found that minimum hip extension torque was 0.7Nm and minimum knee extension torque was 0.9Nm. The minimum hip and knee extension torque required for N-Stand corresponds to a mean 27% and 30%, respectively, of the actual maximum hip and knee extension torque. PMID- 8215864 TI - Feedback of ankle joint angle and soleus electromyography in the rehabilitation of hemiplegic gait. AB - A computer-assisted feedback system was developed to present to walking subjects instantaneous feedback of their muscle activity or joint angular excursions during gait. Targets for muscle activity or joint motion were displayed on the feedback screen along with timing cues that prompted muscle activity or joint flexion/extension at specific times during the gait cycle. The purpose was to compare the effectiveness of joint angle and electromyographic (EMG) feedback to a focused program of physical therapy for gait. Eight hemiplegic stroke patients were treated with ankle joint angle feedback, EMG biofeedback from the soleus muscle, and conventional physical therapy for gait in a three-period crossover design. PT was given either first or last in the sequence of treatments. Gait analysis prior to and following each type of treatment revealed that the feedback treatments resulted in significant increases in stride length and walking velocity and in positive changes in push-off impulse, gait symmetry, and standing weight-bearing symmetry, as evaluated in a general linear model and paired t tests. Overall, physical therapy produced no significant changes. However, when physical therapy was the first treatment of the sequence, significant increases in stride length and velocity were observed. When physical therapy was last, there were significant negative changes in gait symmetry and standing weight bearing symmetry, and negative trends in stride length, walking velocity, and push-off impulse. It is concluded that computer-assisted feedback is an effective tool for retraining gait in stroke patients. PMID- 8215865 TI - Visual influence on center of contact pressure in advanced Parkinson's disease. AB - The visual influence on upright posture was studied in seven patients with Parkinson's disease (PD), Yahr stage III to IV, and seven age-matched controls. The position of the center of contact pressure (CCP) between the feet and floor was analyzed by a photoelastic method. When the patients' eyes were closed, the CCP position shifted significantly backward in PD (open, 48.6 +/- 7.6%; closed, 45.0 +/- 4.8%; p < 0.01), whereas in controls, it shifted significantly forward (open, 45.5 +/- 5.8%; closed, 48.9 +/- 2.8%; p < 0.05). PD patients put their body weight less on the more affected foot (open, 49.6 +/- 4.5%; closed, 47.0 +/- 4.8%; p < 0.01) and more on the less affected foot (open, 50.4 +/- 4.5%; closed, 53.0 +/- 4.8%; p < 0.005), when the eyes were closed. Visual information is important in maintaining the upright posture in PD patients. PMID- 8215866 TI - Reliability of goniometric measurements and visual estimates of ankle joint active range of motion obtained in a clinical setting. AB - We examined intratester and intertester reliability for goniometric measurements of ankle dorsiflexion (ADF) and ankle plantar flexion (APF) active range of motion (AROM). Parallel-forms intratester reliability for ankle AROM measurements obtained by the universal goniometer (UG) and by visual estimation (VE) and intertester reliability for VE of ADF and APF were examined. Repeated measurements were obtained on 38 patients with orthopedic problems by 10 physical therapists in a clinical setting. For intratester reliability of measurements obtained with UG, intraclass correlation coefficients (ICC) for all physical therapists were 0.64 to 0.92 (median, 0.825) for ADF and 0.47 to 0.96 (median, 0.865) for APF. Intertester reliability was quantified with use of ICC. ICCs for measurements obtained by UG were 0.28 for ADF and 0.25 for APF; ICC of VE for ADF was 0.34 and was 0.48 for APF. ICC for parallel-forms intratester reliability obtained with UG and VE ranged from 0 to 0.94 (median, 0.58) for ADF and 0 to 0.86 (median, 0.625) for APF. Thus, a physical therapist should use a goniometer when making repeated measurements of ankle joint AROM. Considerable inconsistency exists when two or more physical therapists make repeated goniometric and visual measurements of ankle motion on the same subject. Physical therapists may erroneously conclude that a patient's AROM has changed because of treatment when the change could be attributed to a lack of intertester reliability. PMID- 8215867 TI - Amantadine-induced coma. AB - Amantadine has found use primarily as an antiviral agent and in the symptomatic treatment of parkinsonism. However, the use of amantadine for the subjective alleviation of fatigue in multiple sclerosis and in the treatment of agitated aggressive behavior in the traumatic brain injured patient has also been described. Side effects of amantadine are primarily related to the central nervous system and include hallucinations, confusion, and nightmares. Toxic manifestations include acute psychosis, coma, cardiovascular toxicity, and death. Amantadine toxicity is a particular problem in patients with renal insufficiency because 90% of an oral dose is excreted unchanged in the urine. We present a case of amantadine-induced coma in a patient with multiple sclerosis and end-stage renal disease. Moreover, this degree of amantadine toxicity was profoundly apparent at a drug level usually not associated with such a severe presentation. PMID- 8215868 TI - Tilt table standing for reducing spasticity after spinal cord injury. AB - A patient with a T12 spinal cord injury and intractable extensor spasms of the lower extremities participated in tilt table standing trial on 5 nonconsecutive days to determine if the intervention would affect his spasticity and spasms. Each day's standing trial was followed by an immediate reduction in lower extremity spasticity (measured using the modified Ashworth scale and pendulum testing). Standing was also accompanied by a reduction in spasms that lasted until the following morning. The reduction of spasms was particularly advantageous to the performance of car transfers. Tilt table standing merits further examination as a physical treatment of spasms that accompany central nervous system lesions. PMID- 8215869 TI - Reflections on the "depressed," "unrealistic," "inappropriate," "manipulative," "unmotivated," "noncompliant," "denying," "maladjusted," "regressed," etc patient. PMID- 8215870 TI - Gasless laparoscopy and conventional instruments. The next phase of minimally invasive surgery. AB - OBJECTIVE: To assess the capability of a retractor system that permits laparoscopic surgery without pneumoperitoneum and to determine if the system facilitates the use of conventional surgical instruments during minimally invasive surgery. DESIGN: Prospective evaluation and data collection with review. SETTING: University-affiliated county hospital. PATIENTS: Twenty-nine male and 29 female subjects evaluated prospectively via 27 trauma-related and 31 elective procedures. METHODS: Fifty-eight laparoscopic procedures were performed between July 1992 and February 1993 with a system consisting of an intra-abdominal fan retractor and an electrically powered mechanical arm using conventional surgical and laparoscopic instruments. RESULTS: Gasless laparoscopy was used in the evaluation of 27 patients with abdominal trauma (11 gunshot wounds, 11 stab wounds, and five blunt injuries). The need for celiotomy was obviated in 20 (74%) of 27 cases. Three enterotomies, two diaphragmatic lacerations, and one gastric perforation were repaired with conventional instruments. Gasless laparoscopic techniques were also used in cholecystectomy (n = 26), diagnostic laparoscopy (n = 3), and appendectomy (n = 2). Exposure similar to that obtained by pneumoperitoneum was obtained in 30 (97%) of 31 cases. One major (trocar tip enterotomy) and two superficial wound infections occurred in this group. The ability to use conventional surgical instruments was advantageous in several cases. CONCLUSIONS: Comparable exposure was achieved in this cohort of patients with gasless laparoscopy. The use of conventional surgical instruments provides an advantage with this technique. Further improvements in abdominal wall lift systems and modification of existing surgical instruments may expand the role of gasless laparoscopy. PMID- 8215871 TI - Practical reduction of transplantation costs. Use of commercial transportation instead of charter aircraft for sharing pancreas grafts. AB - OBJECTIVE: To demonstrate cost savings in pancreas transplantation through use of commercial organ transportation. DESIGN: Retrospective study. SETTING: Independent Organ Procurement Organization, Denver, Colo. SUBJECTS: Forty-three consecutive pancreas grafts recovered by Colorado transplantation surgeons and transported via charter aircraft (53.4%) or commercial airlines (46.6%) to transplantation centers outside Colorado. MEASUREMENTS: Actuarial graft survival at 1 year was calculated. Transportation costs were also obtained. MAIN RESULTS: Transportation of organs via charter aircraft cost an average of $3658.37 compared with an average of $102.40 for commercial airline transportation (average cost difference, $3555.97). Graft survival was 73.9% for chartered grafts vs 80.0% for commercially shipped grafts. Mean preservation times were 13 hours 54 minutes for chartered grafts vs 17 hours 50 minutes for commercial transportation. CONCLUSION: Our data demonstrated a significant cost savings when pancreas grafts were transported via commercial airlines instead of chartered aircraft. These cost savings were obtained without negative sequelae in clinical outcome, encouraging widespread use of commercial airlines for transporting shared pancreas grafts. PMID- 8215872 TI - Anticoagulation followed by elective carotid surgery in patients with repetitive transient ischemic attacks and high-grade carotid stenosis. AB - OBJECTIVE: To evaluate the results of preoperative heparin therapy followed by carotid surgery for patients with repetitive transient ischemic attacks (TIAs) and high-grade carotid stenoses. DESIGN: A 4-year prospective study. SETTING: Oregon Health Science University Hospital and Portland (Ore) Veterans Affairs Hospital. PATIENTS: Twenty-nine consecutive patients with repetitive TIAs referable to 30 high-grade (> or = 70%) ipsilateral carotid stenoses were treated with short-term heparin anticoagulation, followed by cerebral angiography, routine preoperative evaluation, and subsequent carotid reconstruction. INTERVENTIONS: Heparin sodium anticoagulation was maintained for a mean of 5 days. Surgical management consisted of 24 standard endarterectomies, five bypasses to the internal carotid artery, and one external carotid endarterectomy. MAIN OUTCOME MEASURES: Primary outcome variables included perioperative hemorrhage, thrombocytopenia, stroke, and death. Secondary outcome variables included carotid occlusion and recurrent TIAs with heparin therapy. RESULTS: One symptomatic common carotid occlusion and one asymptomatic internal carotid occlusion occurred during preoperative heparin therapy. Thirteen patients had additional sporadic TIAs while receiving heparin. There were no preoperative cerebral infarcts, thrombocytopenia, or clinical bleeding associated with heparin therapy. There was one postoperative stroke and one death due to myocardial infarction. CONCLUSION: When necessary, heparin anticoagulation and delayed carotid reconstruction would appear to be an acceptable alternative to emergency carotid surgery in patients with high-grade carotid stenosis and acute repetitive TIAs. PMID- 8215873 TI - Transfusion significantly increases the risk for infection after splenic injury. AB - OBJECTIVES: To determine if splenectomy results in an increased risk for perioperative infection when analyzed against splenic repair and to identify factors associated with perioperative infection, respiratory complication, and admission to the intensive care unit following surgery for splenic trauma. DESIGN: Data were collected retrospectively from hospital records and analyzed using stepwise multiple logistic regression. SETTING: San Francisco (Calif) General Hospital, an urban level 1 trauma center. PATIENTS: All patients (n = 252) undergoing operation for traumatic splenic injury at San Francisco General Hospital from 1984 through 1990. Patients who died within 24 hours of presentation were excluded from the study. MAIN OUTCOME MEASURES: Perioperative infection, respiratory complications, and admission to the intensive care unit. RESULTS: Infection rates and the types of organisms yielded in cultures were similar between patients who underwent splenectomy and repair. Gram-negative and gram-positive organisms were found in equal numbers, and in no group did encapsulated organisms predominate. Splenectomy had no independent impact on any of the three outcome measures. Total blood transfusion was found to be the only independently significant variable associated with perioperative infection and respiratory complication. Total blood transfusion of more than 2 U and Injury Severity Score of greater than 25 were independently significantly associated with admission to the intensive care unit. CONCLUSIONS: The choice between splenectomy and splenic repair does not affect the risk for perioperative infection following injury, whereas blood transfusion significantly increases the risk for perioperative infection, respiratory complication, and admission to the intensive care unit. PMID- 8215874 TI - Definitive surgery for breast cancer performed on an outpatient basis. AB - OBJECTIVE: More than 160,000 women will develop breast cancer in the United States during the next year. Traditionally, their definitive surgery has been performed on an inpatient basis, with postoperative hospital stays ranging from 1 to 7 days. DESIGN: Retrospective review of cases and results. PATIENTS: Two hundred twenty-one patients underwent 223 definitive surgical procedures for carcinoma of the breast, entirely on an outpatient basis, between September 1990 and June 1992. Operations included 31 modified radical mastectomies, 101 partial mastectomies with radical axillary node dissections, 11 total mastectomies, 69 partial mastectomies, and 11 radical axillary dissections. RESULTS: There were no deaths, and no serious complications. No patient required hospitalization for any reason. There were no wound infections. Patient satisfaction was high, and compliance was excellent. CONCLUSIONS: Most operations for carcinoma of the breast can be performed on an outpatient basis, without increasing the risk of complications. PMID- 8215875 TI - Gastric surgery in morbid obesity. Outcome in patients aged 55 years and older. AB - OBJECTIVE: To evaluate long-term outcome of gastric restrictive surgery in morbidly obese patients aged 55 years and older. DESIGN: Retrospective review with 3- to 13-year postoperative follow-up. Average follow-up 6 years. SETTING: Private surgical practice with bariatric surgery specialty. STUDY PARTICIPANTS: Eighty-eight morbidity obese patients, 73 women and 15 men, aged 55 years and older. INTERVENTION: Between 1977 and 1989, 77 patients had Roux-en-Y gastric bypass, four had vertical banded gastroplasty, and seven had silicone ring vertical gastroplasty. MAIN OUTCOME MEASURES: Weight loss, change in incidence of comorbidity, and reduction in medication use. RESULTS: Patients had an average of 57% excess body weight loss, lost 31 kg, and decreased their body mass index by 12 kg/m2. There was a 20% to 48% reduction in the number of patients requiring medication for obesity-related disorders (eg, diabetes mellitus and hypertension). Body mass index of less than 30 kg/m2 was achieved and maintained by 42% of patients. CONCLUSION: This form of therapy is appropriate for selected patients in the older age groups. PMID- 8215876 TI - Predictors of outcome in patients who have sustained trauma and who undergo emergency thoracotomy. AB - OBJECTIVE: To reassess the use of emergency thoracotomy in resuscitating victims of abdominal or thoracic trauma. DESIGN: Retrospective review of records and autopsy reports of patients who underwent an emergency thoracotomy between 1983 and 1989. SETTING: Washington Hospital Center's Level I trauma center. PATIENTS: Two hundred eighty-four hemodynamically unstable trauma patients (212 [75%] with penetrating injuries and 72 [25%] with blunt injuries). INTERVENTION: Emergency thoracotomy performed in the trauma operating room or in one of the trauma bays. MAIN OUTCOME MEASURES AND KEY FINDINGS: In which subset of trauma patients is emergency thoracotomy a useful therapeutic modality? Performance of an emergency thoracotomy for blunt trauma resulted in an overall survival rate of 6% compared with 27% for penetrating trauma. The survival rate for patients with penetrating cardiac trauma was 32% (44% for stab wounds and 21% for gunshot wounds). Tamponade is a major factor associated with survival in this subset of patients and may act as a pathophysiologic filter. CONCLUSIONS: Emergency thoracotomy is a useful therapeutic modality for victims of penetrating trauma who have vital signs on admission to the hospital, and it should be considered in blunt trauma patients who present with any evidence of life. This modality is largely ineffective, however, in resuscitating victims of penetrating and blunt trauma who present to the hospital without vital signs. PMID- 8215877 TI - Reoperation for bleeding in trauma. AB - OBJECTIVE: Analysis of the causes and clinical patterns of postoperative bleeding requiring reoperation in trauma patients. DESIGN AND SETTING: A case series of 166 consecutive patients treated over 7 years at a level I trauma center. PATIENTS: 136 patients (82%) sustained penetrating trauma, primarily gunshot wounds (102 patients). On admission, 85 patients (51%) were hemodynamically unstable. INTERVENTION: 196 reoperative procedures were performed to control bleeding: 136 laparotomies, 49 thoracotomies, five neck explorations, and six peripheral vascular operations. Results of nine explorations were negative. MAIN OUTCOME MEASURE: Of 157 initial attempts to affect hemostasis, 36 (23%) failed. Twenty-seven patients died of uncontrolled bleeding and 19 died despite successful hemostasis. The overall mortality rate was 28%. RESULTS: Major causes of bleeding were incomplete hemostasis (46%), missed injuries (30%), and iatrogenic complications (17%). Diffuse oozing occurred in only seven of 43 patients with abnormal coagulation. The liver (19 patients) and retroperitoneum (13 patients) were the most common sites of incomplete hemostasis. Missed injuries occurred mainly in the chest wall arteries (seven patients) and heart (six patients). Iatrogenic injuries most commonly involved the spleen (nine patients). CONCLUSIONS: The management of postoperative hemorrhage in trauma hinges on an early decision to reexplore, preoperative correction of abnormal coagulation, and knowledge of specific bleeding patterns. PMID- 8215878 TI - Use of erythropoietin and parenteral iron dextran in a severely anemic Jehovah's Witness with colon cancer. AB - A Jehovah's Witness presented with colon cancer and profound anemia. On admission, her hemoglobin level was 30 g/L (3.0 g/dL). She refused all transfusions and failed to respond to oral iron therapy. She was ultimately prepared for surgery using recombinant human erythropoietin, iron dextran, and total parenteral nutrition. It took nearly 1 month to increase her hemoglobin level to an acceptable preoperative level of 110 g/L (11.0 g/dL). During the postoperative period, erythropoietin and parenteral iron therapy were briefly continued and a follow-up hemoglobin level of greater than 120 g/L (12.0 g/dL) was observed. Recombinant human erythropoietin, along with parenteral iron and adequate nutrition, may be useful in patients who refuse transfusion or cannot be transfused because of difficult cross-reacting antibodies. PMID- 8215879 TI - Laparoscopic surgeon's thumb. PMID- 8215880 TI - Probiotics and manipulation of rumen development and function. AB - There is good evidence that the bacterial and fungal probiotics are effective in the manipulation of rumen development and function. The effects of adherent Streptococcus bovis preparations were manifested by significant increase of adherent S. bovis bacteria and alpha amylase activity in the rumen wall of young ruminants. Fungal probiotics based on Saccharomyces cerevisiae and Aspergillus oryzae are rapidly gaining acceptance as a means of improving productivity in adult ruminants. However, fungal probiotics may also have a complementary role to bacterial probiotics in young animals. Dietary yeast improved performance of calves and lambs in terms of feed intake and live weight gain and Aspergillus foetidus was effective in altering rumen fermentation in newly weaned lambs. PMID- 8215881 TI - Predictions of protein digestibility and lysine absorption in pigs. AB - With 294 feedstuffs-classified into 22 feedstuff categories-, from which in the original literature besides the crude protein (CP) and lysine (lys) contents their precaecal (pc) and partly their total (t) digestibilities in pigs had been presented, assessments of the pc and t apparent digestibilities (AD%) were done by two different ways. Between the prediction possibility using the mean value of nondigestible CP resp. lys (mean ndCP, means ndlys, g/kg DM) and the usual way of calculating average digestive coefficients (mean ADCP%, mean ADlys%) there were with regard to the validity of predictions only small differences, with the tendency of partly more advantageous results by the first cited procedure. Good assessments of pc ADCP% and pc ADlys%, where 70 ... 100 per cent of the single feedstuffs showed prediction errors of only < or = 5 digestibility units, were got for the protein concentrates field bean, lupin, soybean meal, sunflower seed meal, rapeseed meal, yeast and casein as well as with some restrictions for sorghum, linseed meal, blood meal and poultry by-product meal. Less reliable and connected with more uncertainties are the pc digestibility predictions for cereals, peas, cottonseed meals, meat (& bone) meals and fish meals: only 20 ... 30 per cent of the single feedstuffs showed good appraisals with differences < or = 5 digestibility units. In the rule t digestibilities can be assessed more exactly than pc digestibilities, for lys these predictions are mostly less precise than for CP. PMID- 8215882 TI - [The effect of oligosaccharides on piglets]. AB - Into the starter of weaned piglets 1% lactitol and 0.2% fructo-, isomalto- or galacto-oligosaccharides were added. After an adaptation period of two weeks the piglets were slaughtered 3 hours postprandial. Compared with control animals in the trial groups urea concentrations in the serum and fermentations in the stomach were lowered, stomach emptying rates increased. Higher volumes and contents were measured in the colon, especially in the upper half, and more lactic acid. PMID- 8215883 TI - Effect of feed-borne pollution with some mycotoxin combinations on broiler chicks. AB - Broiler chicks were divided into five groups and fed starter mash from the first day after hatching. The first group feed (control) was mycotoxin free, whereas the mycotoxins sterigmatocystin (350 ppb) and aflatoxin B1 (100 ppb) were added to the second group diet, patulin (100 ppb) and aflatoxin B1 (100 ppb) to the third group feed, penicillic acid (850 ppb) and aflatoxin B1 (100 ppb) to the fourth group, and aflatoxins B2a (0.9 ppb) +G2 alpha (25 ppb) +M1 (0.9 ppb) +M2 (1 ppb) to the fifth group. This contaminated feeding lasted for four weeks followed by another four weeks as recovery period during which all groups fed finishing mash without mycotoxins. At the end of the experiment, the chickens of groups two, three, four and five were significantly lower in body weight and feed conversion and reflected higher mortality rates than those of the control group. PMID- 8215884 TI - Effect of virginiamycin on feed intake, daily gains, ruminal volatile fatty acids and blood parameters in veal calves. AB - The effect of a peptolide antibiotic virginiamycin on the growth, rumen and blood parameters was followed in 8 milk-fed calves, 4 weeks old initially. Calves were individually housed in metabolic cages. The experiment was ended at the age of 16 weeks. Virginiamycin was supplied at 80 mg per head per day. Calves receiving virginiamycin gained 5.1% more than control calves. Feed intake per 1 kg of body weight gain was higher in control calves. Virginiamycin significantly increased molar percentage of propionate and decreased molar acetate: propionate ratio in rumen fluid. Serum iron, hematocrit and hemoglobin were significantly increased in the treated group in the last period of the trial. Virginiamycin lowered serum protein and urea and tended to decrease activity of aminotransferases. PMID- 8215885 TI - Study on the energy and protein requirements in goats. AB - The present study focussed on the energy and protein metabolism in pregnant and lactating goats, including young female goats up to 8 months of age, in order to determine feed availability, as also the energy and protein requirements. It was found that the diets consisting of alfalfa hay, oats hay, maize, wheat bran and mixed feeds (fed to suckling females) had different availabilities in terms of energy and protein, according to animal physiological condition and age. Thus, in pregnant goats, 21% of the metabolizable energy (ME) was used as net energy for pregnancy (foetus plus foetal membranes); the amount of energy required for maintenance was 0.400 MJ/kg 0.75. The availability of digestible protein in the intestines (PDI) for pregnancy was 41.2 +/- 3.1%, while the amount of protein required for maintenance was 2.32 g PDI/kg 0.75. In lactating goats 60.7% of the ME of the diets is used as milk net energy, and 58.9 of the PDI as milk protein. Young female goats had a daily net gain ranging between 173 g and 60 g; the amount of protein in the gain varied between 23 g (month 2) and 12 g (month 8); and that of fat, between 8 g (month 1) and 24 g (month 6). The energy and protein requirements for maintenance were found to be 0.450 MJ ME/kg 0.75 and 2.43 g PDI/kg 0.75, respectively. The net efficiency of ME for growth was of 46.2 +/- 3% and of PDI for protein retention, of 50.1 +/- 2%. PMID- 8215886 TI - [Comparative studies of the parameters of rumen fermentation and the digestibility of feed rations in cattle and sheep. 2. The digestibility of feed rations]. AB - The results from 283 comparisons of digestibility in cattle (ox, cow, male and female young cattle) and sheep (adult wether) are presented. The crude protein content of the applied rations ranged from 90 to 340 and the crude fibre content from 80 to 430 g/kg DM. Within the range of rations with 200-350 g crude fibre per kg DM the differences between adult cattle and wether in the digestibility of energy and organic matter don't exceed 1%-unit (mean -0.5 +/- 2.5), that of crude protein is 5%-units lower in adult cattle than in adult wether. In young cattle digestibility is altogether lower than in wether; in young cattle with 120 to 200 kg live weight 4 to 6 and in more developed cattle 3 to 4 digestibility units for energy. In the metabolizability of the energy in comparison between adult wether and the different animal categories of cattle the difference don't exceed 1.5% units. Relations between the live weight of cattle, the crude fibre of the rations as well as the nutrition level and the amount of difference of digestibility between cattle and sheep are considered. PMID- 8215887 TI - [The nutritive efficiency of Bacillus cereus as a probiotic in the raising of piglets. 1. Effect on the growth parameters and gastrointestinal environment]. AB - In an experiment with 4 x 12 piglets the probiotic effect of the Bacillus cereus strain FH 1457 S on the performance and changes in the gastrointestinal tract was studied. Beside a negative control the feed was supplemented with 10(7), 10(8) and 10(9) CFU Bacillus cereus/kg. The experiment included two feeding periods, whereby in the first a prestarter and in the second a piglet rearing feed was administrated ad libitum with the animals kept individually in cages. Over the whole feeding trial the piglets with the additions of 10(7), 10(8) und 10(9) CFU Bacillus cereus/kg feed showed higher daily weight gains of 9.5%, 11.1% and 8.6% with an increased feed consumption of 11.1%, 11.0% and 7.9%. The feed conversion rate was not influenced by the additions. In the first period daily weight gains were increased by 8.9%, 14.7% and 7.8%, the feed consumption in this period was 10.2%, 12.1% and 7.2% higher than in the control group. The addition of 10(8) CFU Bacillus cereus had a significantly higher daily weight gain in the first period compared to the control and the feed conversion rate was improved by 2.4%. In the second period the daily weight gains were increased by 9.9%, 8.9% and 9.1%, the feed consumption by 11.4%, 10.5% and 8.8% because of Bacillus cereus addition to the feed. The frequency of diarrhea was not influenced by the treatments. In each Bacillus cereus dosage the concentrations of ammonia, lactate and volatile fatty acids in small intestine contents were mostly diminished. In caecum contents the concentrations of acetic and propionic acid were decreased in the groups supplemented with Bacillus cereus. PMID- 8215888 TI - [Dependence of gross energy, digestive energy and metabolizable energy of feed and the energy disposition on the content of digestible nutrients in relation to starch and sugar. The progress of energetic feed evaluation. 1. Results from studies on swine]. AB - On the basis of an analysis of energy metabolism measurements on adult pigs, fed on 92 ratios with very heterogeneous nutrient composition, the following prediction equations for gross energy (y1), digestible (y2) and metabolizable energy (y3) as well as for energy deposition effect of ratios (y) (kJ) are presented: y1 = 23.6z1 + 39.8z2 + 17.3z3 + 16.0z4 + 18.9z5 y2 = 23.6x1 + 39.8x2 + 17.3x3 + 16.0x4 + 17.2x5 y3 = 20.5x1 + 39.8x2 + 17.3x3 + 16.0x4 + 17.0x5 y = 11.0x1 + 34.0x2 + 12.7x3 + 11.6x4 + 5.0x7 + (12.0-0.14(80-x6))(x5-x7) [table: see text] PMID- 8215889 TI - [The labeling of feed with 15N as a possibility for the determination of the true N-loss during in situ studies in the rumen of sheep]. AB - Green rye (fertilized with 15N) with 37.4% crude fibre, 6.2% crude protein in DM; and 0.31 Atom-%15N-excess (15N') was separated into the fractions stem, leaves and ear. In the same order the fractions had 39.3, 36.4, 27.8% crude fibre; 3.7, 8.1, 11.4% crude protein in the DM and 0.30, 0.27, 0.33 atom-%15N'. Differences in the 15N-label between different nitrogen fractions for one part of the plant (total-N, TCA-precipitable N, pepsin insoluble N) were also measured. The reasons for these results are the once head-fertilization with N and 15N and the following 15N-turnover in the plant. The disappearance rate of DM, N and 15N of different parts of the rye plant was measured using the nylon bag technique in the rumen of sheep. The disappearance rate after a 24-hours incubation period was in the order whole plant, stem, leaves and ear as follows: DM = 44.4; 40.7; 50.3 and 71.6% N = 39.0; -8.5 (N-influx); 55.0 and 80.1% 15N' = 88.4; 84.0 88.3 and 92.4% The label of the N-fraction in the residues of bags was differently reduced in the fractions of plant as a result of influx of foreign N. The largest effect was found for the residues of stem. The reason for this result was interpreted with strong processes of adsorption in the fibrous material for N-molecules and N compounds. A negatively linear correlation was found between the measured N disappearance after incubation and the relative differences between the values of the 15N- and N-disappearances. These relative differences achieved negligible values when the N-disappearance was about 80%. The labeling of feedstuffs with 15N is a useful method for the estimation of true N-disappearance in experiments with the nylon bag technique. PMID- 8215890 TI - Effects of various supplements on voluntary intake and performance by growing cattle consuming forage moderate to high in crude protein. AB - Growing cattle were supplemented with substances to lessen or increase ruminal ammonia level to determine if consumption of moderate- to high-crude protein (CP) forage is limited by high ruminal ammonia absorption. In Experiment 1 (5 x 5 Latin square), five Holstein steers (198 kg) had ad libitum access to alfalfa cubes (17% CP) without supplementation or with corn at 0.25 or 0.75% body weight (BW) alone (LC or HC) or with 0.06% BW of zeolite (chabazite; LC-Z and HC-Z). Total daily organic water (OM) intake was not affected by treatment (6.08, 6.14, 6.11, 6.19 and 6.09 kg for control, LC, LC-Z, HC and HC-Z, respectively; SE 0.25). In Experiment 2, Simmental crossbred beef calves grazed fescue-clover paddocks in the spring (clipped forage: 21 to 27% CP) for 84 days and were supplemented with 0.25 or 0.75% BW corn alone or with added zeolite (0.06% BW) or lasalocid (0.5 mg/kg BW). Daily gain did not differ among treatments (1.24 to 1.31 kg/day). In Experiment 3 (6 x 6 Latin square), six Holstein steer calves (168 kg) had ad libitum access to medium-quality, orchardgrass-clover hay (15% CP). Steers received one of the following six treatments: no supplement (Control), 0.35% BW ground corn (C), corn plus 0.049% BW urea (C-U), 0.35% BW soybean meal (S), 0.205% BW feather meal (F) or 0.103% BW feather meal, 0.052% BW blood meal and 0.067% BW corn gluten meal (F-BG). Total daily OM intake was 5.00, 5.14, 5.00, 5.11, 4.84 and 4.70 kg for control, C, C-U, S, F and F-BG, respectively (SE 0.13). In Experiment 4 (6 x 6 Latin square), six Holstein steer calves (226 kg) were fed 0.75% BW of alfalfa cubes (19% CP) plus ad libitum access to medium- to high-quality orchardgrass hay (16% CP). Steers received one of the following six treatments: no supplement (Control), corn at 0.25% BW alone (c) or mixed with 0.12% BW peanut skins (C-PSK), a mix of high-CP feedstuffs high in ruminal escape protein (0.029% BW blood meal, 0.038% BW corn gluten meal and 0.028% BW feather meal; C-REP), 0.139% soybean meal (C-S) or soybean meal plus peanut skins (C-PSK-S). Total daily OM intake was 6.16, 6.25, 6.13, 6.52, 6.50 and 6.60 kg for control, C, C-PSK, C-REP, C-S and C-PSK-S, respectively (SE 0.10).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8215891 TI - [The use of a hydrolysis residue from lysine production in a straw concentrate mixture for fattening lambs]. AB - The validity of residues from hydrolysis of soya bean meal for production of lysine was tested in a growth experiment with 2 groups of 25 cross breeding lambs as well as in a N-balance trial with 5 lambs. The animals in the growth experiment started with an average body weight of 25 kg. An industrially produced concentrate for lamb fattening was given to the animals of the control group. To the second group a straw-concentrate mixture was given, containing 30% straw, 52% barley, 5% soya bean meal, 5% dried beet pulp and 5% of hydrolysis residue. The mixture included 10.71 MJ ME resp. 5.51 MJ net-energy fat (cattle) and 166 g digestible crude protein per kg dry matter. The lambs of group 2 showed an 8% lower intake of DM, connected with a 26% intake of energy and 32% lower intake of DCP in comparison to the control group. The average daily body weight gain was 374 g for the control group and 241 g for group 2 respectively, the difference being statistically significant. The feed/gain ratio was in group 2 = 14% higher for energy and 6% higher for DCP than in the control group. The N-balance trial resulted in a N-retention of 25 percent of the N-intake. The results approved the possible use of 5% of the hydrolysis residue product for 2% crude protein in straw-concentrate mixtures for ruminants. PMID- 8215892 TI - Effect of partially substituting concentrate feed mixture by either fresh or waste oil in sheep diets. AB - Seven digestibility trials were carried out on sheep to study the effect of replacing concentrate feed mixture (CFM) with varying amounts of fresh (raw) sunflower oil or heated oil from bean cake (Taamiah) frying, in almost isocalorific and isonitrogenous diets. Boiling altered the physical and chemical properties of oil but not significantly except for the peroxide value (P < or = 0.05). Substitution with fresh oil significantly increased the digestibility of nutrients, whereas the boiled lead to conflicting results where all the digestibilities tended to decrease. The feeding value was also affected by the addition of oil. The blood analyses of the animals reflected biochemical changes indicating some dysfunction of the internal organs, in particular the liver showed signs of hyperlipidaemia and hypercholesterolaemia. It was concluded that the loss of CFM energy could be partly substituted by fresh oil or by a small amount of waste oil. PMID- 8215893 TI - [The effect of the protein level of food on the energy maintenance requirement of growing rats on different feeding regimens]. AB - Male Wistar rats were fed in the live weight range between 70 and 200 g in periods alternately for maintenance and weight gain (semi ad libitum). The diets contained 10, 40 and 70% crude protein, resp., the ambient temperature was 30 degrees C. In agreement with two previous experiments 2 different feed regimes were used. Whereas in the first growth phase (up to about 150 g live weight) the supply of protein was constant for each group, in the second growth phase the protein level was changed between the groups from one period to the other. The energy metabolism on the feeding level of maintenance was measured by indirect calorimetry. At both feeding regimes a dependence of energy maintenance requirement on the protein level of feeding was established. The differences in the maintenance requirement between the 10% and 70% protein level and in the first growth phase also between the 10% and 40% protein level corresponded on average to a growth phase the expected values of which result from the different efficiency of ATP synthesis in the oxidative degradation of nutrients. It follows that--in accordance with the previous findings--the feeding regime does not influence the ratio of energetic utilization of nutrients in the maintenance metabolism of growing rats under the experimental conditions used by us. Further the results of all our studies on the dependence of the energy maintenance requirement of growing rats on the nutrient composition are summarized. We conclude that a dependence on the protein-carbohydrate ratio of the diet according to the different efficiency of ATP synthesis in the protein and carbohydrate catabolism can be reproducibly established by our experimental methods only then, if more than 50% of the energy maintenance requirement are covered from protein energy. PMID- 8215894 TI - [The passage, absorption and secretion of nitrogen during the postprandial period using 15N-labeled wheat and marker in growing rats]. AB - After a 9 day preparation period 42 Wistar rats (live weight 100 g) were fed a diet of 15N labelled wheat supplemented with the marker TiO2 (impulse labelling). At 7 time intervals (0.5 to 6 h after feeding) 6 animals were killed and thereafter total N, 15N and TiO2 levels were estimated in the digesta of different intestinal sections. The following results were obtained: The transit rate of the marker amounted to 10.3 +/- 0.62% per hour of the intake. The endogenous part of N increased during passage from stomach (3.5%) to duodenum (38.6%), jejunum (59.1%), ileum (64.8%), large intestine (78.3%) and faeces (87.7%). The apparent N digestibility in the stomach increased with time reaching 26% 6 h after feeding. In the whole small intestine it was 66.3%, in the ileum 78.9% and in the large intestine 90.4%. The true digestibility (6 h after feeding) showed the same course, but was always some units higher (stomach 33.3%, whole small intestine 82.5%, ileum 92.2% and large intestine 93.5%). Apparent and true digestibility values in the ileum correspond best to the data of precaecal digestibility; those of the large intestine correspond to the postileal digestibility. The N disappearance rate in the stomach is the sum of absorption rate (16%/h) and transit rate into the small intestine (12.4 +/- 1.6 mg N/h). Most absorption occurred during passage through the small intestine (2/3 of total absorption). The absorption in the small intestine was about 80% of the N amount flowing from the stomach into the intestine. The amount lay between 18.2 and 26.1 mg N/h and half of this was of endogenous origin. The reabsorption rate of endogenous N for the whole intestinal tract was estimated to be 91.4%. The N secretion into the whole intestine increased during the 6 h after feeding up to 85.5 mg (64% of N intake), for which 77 +/- 5.5% was secreted into the small intestine. Secretion into the stomach was relatively small and up to 4 hours after feeding, amounted only to 3.0 ... 6.7 mg N. PMID- 8215895 TI - [The nutritive effect of Bacillus cereus as a probiotic in the raising of piglets. 2. Effect and microbial count, composition and resistance determination of gastrointestinal and fecal microflora]. AB - After a feeding trial of 42 days with 4 x 12 piglets 4 x 6 piglets were slaughtered and the influence of spores of the Bacillus cereus strain FH 1457 S added to the feed on the microorganism counts of Lactobacillus/Bifidobacterium, Eubacteria, Bacteroidaceae, E. coli, Enterococcus and passants (Bacillus cereus) in duodenum, jejunum, ileum, caecum and colon was investigated. Beside a negative control the feed was supplemented with 10(7), 10(8) and 10(9) CFU Bacillus cereus/kg. The feeding trial included two periods each of 21 days. In each period faeces was collected from all animals and the influence on the microorganism counts and also the frequency of resistance of the E. coli and Enterococcus germs against selected antibiotics and chemotherapeutics investigated. The addition of 10(8) CFU Bacillus cereus decreased E. coli counts in duodenum and jejunum, however increased them in ileum, caecum and colon. In the highest dosage the counts of Bacillus cereus in duodenum, caecum, colon and faeces were significantly higher. The addition of Bacillus cereus reduced the counts of E. coli and Enterococcus in faeces in the first period. In the second period the dosage 10(8) CFU showed significant increased counts of E. coli and the sums of microorganisms of the main and satellite flora. The additions had no influence on the frequency of resistance of E. coli and enterococci against the tested antibiotics and synthetic chemotherapeutics. From the addition of Bacillus cereus in this case a selection of factors influencing resistance is not to be expected. PMID- 8215896 TI - Development of rumen metabolism and ruminal epithelium in lambs. AB - The concentrations of volatile fatty acids and the development of rumen epithelium and microflora adhered to rumen wall in suckling lambs were observed. Total VFA concentration increased with age. The differences between the 1st (28.5 mmol.l-1) and 4th week of age (78.7 mmol.l-1) and between 6th (82.1 mmol.l-1 and 10th week of age (117.4 mmol.l-1) were significant (p < 0.01). The highest molar proportion of acetic acid (71.2 mol%) was observed in 1 week-old lambs and the highest molar proportion of propionic acid in 6 week-old lambs (20.8 mol%). Length and surface characteristics of papillae changed dramatically over the 10 week period. In samples from 1-week and 4-week-old lambs, the papilla surface was relatively smooth and epithelial cells were relatively thin and flat. In samples from 6-week and 10-week-old lambs the tissue topography was typically rough. In the 1-week-old lambs the cocci, single rods and short rods in pairs were present at very low population levels. At 4 weeks the epimural community became notably more complex and bacteria were present at a higher population level. The dominant morphotype at 6 weeks was a rod-shaped end-on attached bacterium. The epimural microflora became the most complex at 10 weeks. PMID- 8215897 TI - [Dependence of gross energy, digestible and metabolizable energy of feed and the energy onset on the content of digestible nutrients in regard to starch and sugar. A contribution to the further development of energetic feed evaluation. 2. Results from studies of cattle]. AB - On the basis of an analysis of energy metabolism measurements on adult cattle (oxen), fed on 110 rations with very heterogeneous nutrient composition, the following prediction equations for gross energy (y1), digestible (y2) and metabolizable energy (y3) as well as for energy deposition effect of rations (y) (kJ) are presented: y1 = 23.6z1 + 34.0z2 + 17.3z3 + 16.0z4 + 19.1z5 y2 = 23.6x1 + 34.0x2 + 17.3x3 + 16.0x4 + 18.0x5 y3 = 17.3x1 + 34.0x2 + 15.9x3 + 15.1x4 + 15.4x5 y = (6.5x + 26.6x2 + 10.1x3 + 7.5x4 + 8.9x5) (-0.5574 + 0.04050x6 - 0.0002633x6(2)) [table: see text] PMID- 8215898 TI - [Effect of bovine growth hormone on performance criteria of dairy cows during summer feeding with grass. 1. Feed intake and protein and energy supply]. AB - The influence of long-term administration of bovine growth hormone (bGH) with prolonged release (Somidibove from Lilly Germany GmbH, section Elanco, 640 mg/28 d) in six consecutive injection periods on feed intake under summer feeding conditions with grass feeding ad libitum was investigated. After a pretreatment period of 22 days 30 dairy cows were divided into 15 blocks with two cows each in consideration of milk yield, days postpartum and number of calving. In each block the bGH-treated animal received the same concentrate supply as the corresponding control animal which was supplemented in order to requirement. In a 42 day posttreatment period without bGH-injection possible effects of bGH-treatment on feed intake (grass silage and maize silage) was investigated. The first injection was administrated 75 days postpartum, respectively. During all six injection periods feed intake corrected to the pretreatment period was increased by 0.63 kg DM/animal.d resulting from a higher grass intake in the bGH-treated dairy cows compared to the control group. This difference in feed intake raises from 0.40 kg DM/animal.d in the first injection period up to 0.84 kg DM/animal.d in injection period six and continued in the posttreatment period without bGH-injection (+0.89 kg DM/animal.d). The higher feed intake of grass in the injection periods by the bGH-treated dairy cows resulted in an increased energy intake sufficient on average for the production of 1.2 kg milk/animal.d. Possibilities and limits of a sufficient nutrient supply in bGH-treated dairy cows by an increasing intake of grass are discussed. PMID- 8215899 TI - [Effect of the starch sources barley, corn and potatoes and their ration portions on nutrient digestibility and energy utilization in ruminants. 3. Energy utilization in cattle]. AB - With investigations on the influence of different starch origins (barley, maize and raw potatoes) and different portions of the starch origins in the rations (50, 25 and 10% of the net energy fat, cattle (NEFr) content of the rations) on the energy utilization of rations a contribution was made to the development of the energetic feed evaluation within Rostock NEF-system. The experiments were carried out with fattened oxen using the methods of total metabolism technique and duodenal passage measurement by means of reentrant fistula. The nutrition levels amounted to 1.7 and 1.1 of energy maintenance requirement. The utilization of metabolizable energy for deposition of the 9 rations-including 3 variants of starch origins barley, maize and raw potatoes with parts in the rations of 50, 25 and 10%--was measured as 65, 61 and 59%, 61, 60 and 58% as well as 59, 61 and 55%. The energy maintenance requirement amounted to 526 kJ ME/kg LM 0.75.d. The gradations of energy utilization are caused by the connection between energy concentration and utilization of rations in ruminants. With comparable parts of the rations the different starch sources had no relevant influence on the energy utilization of the rations. Despite a wide range of starch plus water soluble carbohydrates (WSC) intake between 896 and 3426 g/animal.d no correlation between the kind of digestion (fermentative or enzymatic) of starch and WSC and the energy utilization of the rations was measurable, because the part of the ruminal digestion amounted to 86.0 and 97.2%. The result presented for the energy and nitrogen metabolism measurements are in good agreement with results of former experiments with 92 rations. PMID- 8215900 TI - Protein degradation in different feedstuffs labelled with 15N by using the nylon bag technique. AB - The nylon bag technique was used to determine the Nitrogen (N) and 15N degradation of 15N labelled feedstuffs in the rumen. The N and 15N degradation values were calculated according to Orskov and McDonald (1979) and ranged from 46.8 to 92.0 and from 61.8 to 93.6%, respectively. The differences between N and 15N degradation values of high fibre content feedstuffs are the highest, thus the measuring errors were greatest here. But differences also existed in concentrates. This study indicated that especially barley had a higher proportion of microbial N in the bag residues after the washing than the other concentrates. Therefore it is necessary to correct the N degradation values not only in cases of high fibre content but also in cases of low nitrogen content of feedstuffs. The calculation of the N degradation values could be possible on the basis of crude fibre and crude protein contents of feedstuffs. But experiments with a much larger number of 15N labelled feedstuffs have to be realized to give an accurate prediction of N degradation. PMID- 8215901 TI - [The energy and nitrogen metabolism of pregnant and lactating sows and suckling piglets. 1. Experimental plan and results concerning the live weight development of pregnant, non-pregnant and lactating sows and the reproductive performance during gestation and lactation]. AB - The aim of the experiments was to work out new results for a factorial derivation of energy and protein requirement. The experiments were carried out according to a 3 x 3 factorial experimental plan with 3 variants of litter number (1, 2 and 4, age of sows) and 3 variants of energy supply (120, 100 and 80% of the norm of pregnancy, continued in lactation with 80, 100 and 120%). Methods of the indirect calorimetry and the slaughtering technique were used. The mean cumulative live weight changes of the sows for the 9 experimental variants amounted from 13.1 to 63.2 kg for the 115 days of pregnancy and from -17.0 to 6.8 kg for the first 26 days of lactation. The chosen variation of energy supply of pregnant and lactating sows had no relevant effect on the reproductive performances, measured by litter size, weight of conception products, litter weight at birth and the quantity of milk per sow and day respectively. In comparison with the sows of litter number 1 the sows of litter number 2 and 4 had higher litter weights at birth and higher milk quantities. PMID- 8215902 TI - [The energy and nitrogen metabolism of pregnant and lactating sows and suckling piglets. 2. Chemical composition and energy content of the animal bodies of pregnant, non-pregnant and lactating sows]. AB - The influence of litter number (1, 2 and 4, age of sows) as well as gestation and lactation stage of sows on the chemical composition and on the quantities of protein and fat of their bodies was investigated. The slaughter of 46 pregnant, 18 non-pregnant and 17 lactating sows were carried out at the 1st, 56th, 84th, 98th, 105th and 113th day of gestation, 113th day of experiment (non-pregnant sows) and 26th day of lactation. The results were related to the sows' energy supply (120, 100 and 80%) with equal supply of protein, vitamins and minerals. Within the tested litter numbers the chemical composition of the bodies was nearly constant during the whole time of gestation and lactation. A good agreement existed for the chemical composition of the sows' bodies of litter number 1 and 2. In comparison to them the bodies of litter number 4 contained more protein and less fat per kg dry matter. The quantities of body protein and fat increased in the gestation and decreased in the lactation period, in each case the quantities of fat exceeded than the quantities of protein. The quantities of body protein increased with higher litter number. The quantities of body fat increased from litter number 1 to 2 and were nearly equal in the sows of litter numbers 1 and 4. Within one litter number the amounts of body protein and fat attained the same level in pregnant, non-pregnant and lactating sows. PMID- 8215903 TI - The biological activity of natural source tocopherols in chickens fed fresh or oxidized fat rich in linoleic acid. AB - Three experiments were carried out with male broiler chickens reared from day- old to 6 weeks of age on semi-purified diets containing 10% fresh (Expt. 1 and 3) or oxidized (Expt. 2) re-esterified triglycerides with a fatty acid composition similar to that of soya bean oil containing increasing concentrations of either a mixture of d-alpha-, gamma-, delta-tocopherylacetate (d-tocopherols) of natural source or dl-alpha- tocopheryl acetate (dl-tocopherol). In Expt. 1 and 2 the mixture of d-tocopherols consisted of 35.7% d-alpha-, 45.3% d-gamma- and 19.0% d delta-, while in Expt. 3 the distribution was 25.3% d-alpha-, 28.1% d-gamma- and 10.8% d-gamma- in 35.8% re-esterified triglycerides. The relative biopotency of d alpha-: gamma-: delta-tocopherol was anticipated to be 100:25:1, whereas that of dl-alpha-tocopherol was 74% relative to d-alpha-tocopherol. The experiments demonstrate that the results obtained for the biological activity depend on the response parameters chosen. With respect to gain in weight, feed conversion, relative organ weight, packed cell volume (PCV), ELP (erythrocyte lipid peroxidation), plasma activities of glutamate-oxaloacetate-transaminase (GOT), creatine kinase (CK) and glutathione peroxidase (GSH-Px) and plasma Na+ concentration, the mixture of natural source tocopherols was identical to that of dl-alpha-tocopheryl acetate, although the concentration of alpha-tocopherol was only about one third of that of dl-alpha-tocopherol. Differences between natural source and synthetic tocopherols were expectedly observed with respect to plasma concentrations of alpha-, gamma-, delta-tocopherol. Differences between the two forms as to muscular dystrophy, in vitro haemolysis and potassium concentration in plasma were ambiguous. It is suggested that the function of d-alpha-, gamma-, delta-tocopherol in erythrocyte fragility and skeletal muscle structure should be compared to that of dl-alpha-tocopherol in future investigations. PMID- 8215904 TI - [The effect of bovine growth hormone on the production criteria of dairy cows during summer feeding with grass. 2. Milk yield, milk composition and live weight]. AB - The influence of long-term administration of bovine growth hormone (bGH) with prolonged release (Somidibove from Lilly Germany GmbH, section Elanco) on milk yields, milk composition and live weights in six following injection periods of 28 days each was investigated. 30 dairy cows were divided into 15 blocks of two, each pair in consideration of milk yield in a preperiod, days postpartum and number of calving. One animal in each block received the bGH treatment (640 mg bGH/28 days). Concentrate feeding of the bGH-treated cows acted according to the control animal in each block. The forage intake from grass was ad libitum. During all six injection periods the bGH-treated cows had a higher milk yield of 1.3 kg/day (P < or = 0.13). Milk fat content was unchanged, milk protein content was in relation to the changes from preperiod significantly higher in the bGH-treated group. Each injection resulted in a curvilinear response curve of daily milk yield, milk fat and milk protein content. Milk lactose content was not affected by the bGH-treatment. PMID- 8215905 TI - [The effect of starch sources barley, maize and potatoes and their ration portions on the nutrient digestibility and energy utilization in ruminants. 4. Nitrogen metabolism in the rumen]. AB - In 9 experimental periods on four adult bulls (LW 550 kg) fitted with re-entrant cannulae in the proximal duodenum isoenergetic rations were used on feeding level 1.7 with ground barley, ground maize or fresh potatoes as starch sources. The net energy parts of these concentrates in the ration amounted to 50, 25 and 10%. 50 to 80% of the ration DM consisted of dried grass and about 10% of sugar beet pulp. The dried grass supplied on an average 87, 79 and 62% of the feed crude protein. The intake of DM was 7.74 +/- 0.42 (mean +/- SD) kg/d. The energetic efficiency of microbial N synthesis in the rumen (g N/kg organic matter true fermented in the rumen, TFOM) was averaged 16.4 with a range of 10.6 to 21.4. The microbial efficiency achieved a maximum when the ratio of nitrogen-free extract to crude fibre in the diet was 1.7 and 2.1 with barley, 1.8 with potatoes and 2.1 and 3.3 with corn as starch source. Changes in the microbial efficiency were positively correlated with the rate of passage of non-microbial organic matter from the rumen (g/d) and with the duodenal flow rate (kg digesta/kg DM intake). The relation to the rate of carbohydrate fermentation in the rumen (in %) and to the amount of TFOM (g/d) was negative. The duodenal flow of microbial N and non ammonia N (g/d) correlated negatively with the organic matter apparently fermented in the rumen (AFOM) and positively with the non AFOM. The amino acid (AA) profile of the duodenal protein was affected by the starch source. It was concluded that the metabolism of nitrogen in the forestomachs of cattle is affected by the source of starch and the ratio of forage to concentrate. There exists a relationship between both factors. The net synthesis of microbial protein in the rumen is not only the result of substrate fermentation. The passage of non-AFOM from the rumen significantly affects the energetic efficiency of microbial nitrogen synthesis and the duodenal supply of AA. PMID- 8215906 TI - In vitro cytochrome P450 monooxygenase and prostaglandin H-synthase mediated aflatoxin B1 biotransformation in guinea pig tissues: effects of beta naphthoflavone treatment. AB - In the present study, we examined the effects of treating guinea pigs with beta naphthoflavone (BNF) on aflatoxin B1 (AFB1) metabolism by microsomal cytochrome P450 monooxygenase (P450) and prostaglandin H synthase (PHS) in liver, lung and kidney tissues. After BNF treatment, microsomal 7-ethoxyresorufin O-deethylase activity was induced 13-, 25- and 11-fold in lung, kidney and liver, respectively, confirming that the BNF treatment protocol was effective at inducing monooxygenase activity. Treatment of guinea pigs with BNF did not change [3H]AFB1-DNA binding catalyzed by microsomal PHS or P450 in lung, kidney or liver. In contrast, AFM1 formation by P450 was significantly increased in microsomes from all three organs. The data indicate that BNF-inducible P450 isozymes of the P4501A class are responsible for the biotransformation of AFB1 to non-toxic metabolites. Guinea pig kidney microsomes could also catalyze NADPH dependent formation of aflatoxicol (AFL), a metabolite usually produced by a cytosolic steroid dehydrogenase. Renal microsomal AFL formation was not altered by prior BNF treatment. The results in the present study suggest that BNF may alter the bioactivation of AFB1 in guinea pig tissues by inducing P450 activity, leading to the formation of less reactive metabolite. PMID- 8215907 TI - Late preventive effects of quinacrine on carbon tetrachloride induced liver necrosis. AB - We have previously reported that treatments stimulating phospholipid (PL) synthesis or preventing PL degradation were late preventive agents against CCl4 induced liver necrosis. Later studies by others postulated that stimulation of phospholipase A2 (PLA2) plays a role in PL degradative processes responsible for CCl4 damage. Quinacrine (QUIN) is a well known inhibitor of PLA2. In this work we report that QUIN (150 mg/kg i.p.) partially prevents CCl4-induced liver necrosis at 24 h when given 30 min before or 6 or 10 h after CCl4 (2.5 ml/kg p.o.) QUIN administration does not modify at 1 or 3 h after poisoning CCl4 levels reaching the liver, covalent binding of CCl4 reactive metabolites to proteins or lipids, CCl4-induced lipid peroxidation process, CCl4-induced decreases in body temperature, or glutathione levels in liver. QUIN concentrations in liver at times from 1 to 24 h are well over those required to inhibit PLA2 activity. Results are compatible with the hypothesis that CCl4 activation of PLA2 at late stages of poisoning plays a role in CCl4-induced liver necrosis. PMID- 8215908 TI - Effect of antimitotic agent colchicine on carbon tetrachloride toxicity. AB - A single administration of a subtoxic dose of CCl4 (100 microliters/kg, i.p.) is known to induce hepatocellular regeneration and tissue repair at 6 and 48 h in rats, permitting prompt recovery from the limited liver injury associated with that dose of CCl4. Substantial evidence has accumulated to indicate that the early-phase hepatocellular regeneration and tissue repair are critical for recovery from halomethane hepatotoxicity. The objective of these studies was to test this concept in an experimental framework, wherein a selective ablation of the early-phase cell division should result in prolongation of liver injury followed by recovery. The studies were designed to evaluate the influence of the antimitotic agent colchicine (1 mg/kg, i.p. in saline) on CCl4 toxicity. Colchicine was administered 2 h prior to CCl4 or corn oil injection. Toxicological end points and markers of hepatocellular regeneration were assessed at various time points (2, 6, 12, 24, 48 and 72 h) after the injection of CCl4 to male Sprague-Dawley rats. Hepatocellular injury was assessed through elevations of serum alanine and aspartate aminotransferase and by histopathological examination of the liver. Incorporation of 3H-thymidine in hepatocellular nuclear DNA and mitotic index were used as indices of hepatocellular regeneration. Hepatocellular regeneration stimulated by CCl4 at 2-6 h was blocked by colchicine as evidenced by the decreased 3H-thymidine incorporation and mitotic index,without any significant effect on the second phase of cell division at 48 h. Ablation of this early phase of tissue repair resulted in prolongation of CCl4 hepatoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215909 TI - Mechanism for the changes in levels of glutathione upon exposure of cultured mammalian cells to tertiary-butylhydroperoxide and diamide. AB - Qualitative and quantitative changes associated with cellular glutatione (GSH) in response to oxidants were investigated in cultured Chinese hamster V79 cells. Incubation of cells with benzoylperoxide (BZP), tert-butylhydroperoxide (t BuOOH), hydrogen peroxide or diamide for 1 h reduced the level of total GSH (GSH + GSSG). Among the oxidants, t-BuOOH and diamide caused an increase in levels of glutathione disulfide (GSSG) and a resultant increase in the ratio of the level of GSSG to the level of total GSH, suggestive of the induction within the cells of a pro-oxidant state by the oxidants. o-Phenanthroline, a chelator of divalent ion, almost completely suppressed the decrease in levels of total GSH caused by t BuOOH while it did not suppressed either increases in levels of GSSG or increases in the ratio of the levels of GSSG to that of total GSH caused by the hydroperoxide. These results suggest that reactive oxygen radicals are involved in the decrease in levels of GSH by treatment with t-BuOOH but not in the increase in the level of GSSG. After treatment with either t-BuOOH or diamide for 1 h, the level of GSH rapidly increased to more than twice the control level during 15-45 min of post-treatment incubation. o-Phenanthroline almost completely suppressed the increase in levels of GSH caused by t-BuOOH, while it did not affect the changes caused by diamide, suggesting a difference between the mechanisms by which t-BuOOH and diamide cause increases in levels of GSH. It seems likely that reactive oxygen radicals participate not only in the decrease in levels of GSH caused by t-BuOOH but also in the rapid increase that occurs after such treatment. Hence, the first decrease in levels of GSH by the hydroperoxide may be causally related to the latter increase. The amount of [35S] cysteine taken up by cells after treatment with t-BuOOH was about one half of that taken up by control cells. By contrast, the rate of incorporation of radioactive cysteine into acid-soluble material increased to more than twice that of the controls after treatment with t-BuOOH. The increase in the rate of incorporation of [35S]cysteine into acid-soluble material caused by t-BuOOH was not a consequence of inhibition by the hydroperoxide of utilization of cysteine for protein synthesis. Inhibition of protein synthesis by cycloheximide caused neither an increase in the incorporation of cysteine into acid-soluble material nor an increase in rate of biosynthesis of GSH.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8215910 TI - Chondrotoxicity of quinolones in vivo and in vitro. AB - Chondrotoxicity is a rare toxicological finding which is observed in dogs after administration of quinolone antibacterials. To study this effect chondrocytes from articular cartilage of dogs were isolated, and incubated with quinolone derivatives. The effects on cell viability, mitochondrial dehydrogenase, and proteoglycan synthesis were determined. These results were compared with in vivo findings in dogs treated with these quinolones. It was concluded that inhibition of mitochondrial dehydrogenase activity and of proteoglycan synthesis are major reasons for cartilage damage. Therefore this in vitro model is capable of identifying strongly arthropathogenic quinolones without the need of performing animal studies. PMID- 8215911 TI - Effect of some metallic cations and organic compounds on the O-hexyl O-2,5 dichlorophenyl phosphoramidate hydrolysing activity in hen plasma. AB - One of the main detoxification mechanisms of organophosphorus (OP) compounds is hydrolysis by OP hydrolysing enzymes (OP-hydrolases) or phosphoric triester hydrolases. We previously reported an OP-hydrolase from hen plasma which hydrolyses O-hexyl O-2,5-dichlorophenyl phosphoramidate (HDCP). In this study, a total of 18 cations, as well as several thiol blocking reagents, ethylenediaminetetraacetic acid (EDTA) and mipafox (N,N'-diisopropyl phosphorodiamidofluoridate) were assayed as activators or inhibitors of the HDCP hydrolysing activity of hen plasma in vitro. Of the 18 inorganic cations only 1 M Na+ caused any inhibition. Most of the cations, including Ca2+, exerted no detectable effect; however, 1 mM Cu2+ was found to produce an activation of up to 263%, with a lesser activation of up to 168% for 1 mM Zn2+. The thiol blocking reagents methyl vinyl ketone (MVK) and N-ethylmaleimide (NEM) inhibited the enzyme in a time-dependent manner, the maximum effect depending upon concentration in the case of NEM, but not in the case of MVK; however, 5,5' dithiobis (2-nitrobenzoic acid) caused inhibition that was concentration dependent but which was independent of time. Other thiol blocking reagents such as p-hydroxymercuribenzoic acid (sodium salt), phenylmercuric acetate, iodoacetic acid (sodium salt) and iodoacetamide produced only slight inhibition, as did EDTA. Finally, the OP compound mipafox exerted no detectable effect. PMID- 8215912 TI - Mercuric chloride-induced alterations of levels of noradrenaline, dopamine, serotonin and acetylcholine esterase activity in different regions of rat brain during postnatal development. AB - Wistar rats were fed mercuric chloride, 4 mg/kg body weight per day chronically from postnatal day 2 to 60 by gastric intubation. Mercury consumption was then discontinued until 170 days to allow time for recovery. Since mercury caused reduction in body weight, an underweight group was also included besides the normal saline group. Levels of noradrenaline (NA), dopamine (DA), 5 hydroxytryptamine (5-HT) and the activity of acetylcholine esterase (AChE) were assayed in various brain regions in different age groups. By 60 days of age, the mercury group showed elevations of NA levels in olfactory bulb (OB), visual cortex (VC) and brain stem (BS) but not in striatum-accumbens (SA) and hippocampus (HI). DA levels were also increased in OB, HI, VC and BS but not in SA. AChE activity was decreased in the mercury group only in HI and VC at 20 days of age. The Mercury group showed no behavioural abnormality outwardly; however, operant conditioning revealed a deficiency in performance. Nevertheless, all these changes disappeared after discontinuation of mercury intake. Thus the changes occurring in the brain at this level of oral mercuric chloride intake seem to reflect adaptive neural mechanisms rather than pathological damage. PMID- 8215915 TI - [Cerebral hemometabolism: from isolated measurements to monitoring and therapy]. AB - An overview is presented on historical and multivariate aspects of cerebral hemometabolism. This involves a full multivariate approach, from blood pressure to cerebral metabolism. From isolated measurements, to monitoring and management, a comprehensive overview of cerebral hemometabolism is addressed, from its inception to current days, up to a new concept, the cerebral hemodynamic reserve. A multivariate functional diagram is proposed, to summarize the multivariate interrelationships of cerebral hemometabolism. A generic proposition is made for studies of truly normal cerebral hemometabolism in children, for subsequent clinical applications. Another proposition is made for multivariate cerebral hemometabolic monitoring, in a broad variety of circumstances of predominantly global changes in intracranial dynamics, both in animal and clinical research. PMID- 8215913 TI - Acute effects of the heavy metal antidotes DMPS and DMSA on circulation, respiration, and blood homoeostasis in dogs. AB - The heavy metal antidotes sodium-2,3-dimercaptopropane-1-sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) were investigated in anaesthetized dogs for their effects on a variety of physiological variables and parameters. In addition, the influence of both dithiols on oxygen consumption and ferrihaemoglobin production was studied in blood and red blood cells in vitro. DMPS (15 and 75 mg/kg i.v.) did not affect respiration, central venous pressure, left ventricular pressure or cardiac output and showed only marginal, statistically non-significant effects on aortic and effective perfusion pressure. In contrast to the slight, non-significant changes due to DMPS (15 mg/kg i.v.), an equimolar dose of DMSA (12 mg/kg i.v.) led to a slight transient decrease in femoral blood pressure with strong reflex tachycardia and increase in blood flow. The higher DMPS dose (75 mg/kg i.v.), however, caused marked decreases in femoral blood pressure and blood flow, strong changes in blood gases and pH, and lactacidosis. Most of the physiological variables and parameters did not return to the initial level by 60 min. The R-spike of the electrocardiogram decreased, and the T-wave increased. Experiments on the denervated hind leg indicate that DMPS may be a direct vasodilator. The fall of blood pressure due to DMPS was markedly reduced when 30% ferrihaemoglobin had been formed by 4 dimethylaminophenol.HCl (DMAP). The highest DMPS dose (150 mg/kg i.v.) provoked circulatory failure and respiratory arrest. Artificial ventilation with room air restored spontaneous respiration, but one of three animals did not survive this dose for more than 90 min. DMPS and DMSA reacted with oxygen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215914 TI - Effect of exposure to 2,5-hexanediol in light or darkness on the retina of albino and pigmented rats. II. Electrophysiology. AB - Albino (Sprague-Dawley) and pigmented (Norwegian Brown) male rats were exposed to 2,5-hexanediol (H; 1%) in their drinking water for 5 or 8 weeks, respectively. Half of the rats of each strain were housed in light (average 30 cd/cm2 inside cage, 12 h/day); the other half was kept in constant darkness. Control groups were studied in parallel under identical conditions but without H. Electrophysiological recordings were made 2-5 days and 13 weeks after the end of the exposure to H. Alterations in the visual system, as measured by electroretinography and visual evoked response, were found in groups of albino rats exposed to H and/or light. The pupillary diameter was enlarged in the albino group exposed to both H and light. Among the pigmented rats, alterations were recorded only in the visual evoked response of the H exposed groups. The results demonstrate that simultaneous exposure to H and light can lead to alterations in visual function that are more severe than those induced by each agent alone, and may exceed a simple summation. PMID- 8215916 TI - [Operational manual of the reaction level scale (RLS85)]. AB - The Reaction Level Scale (RLS85) is a range scored coma scale (8 levels) for the assessment of responsiveness in patients with acute brain disorders. Its feasibility in clinical practice and for research studies has been verified in a multicentre study and by comparison with other current coma scales. Range scoring and absence of pseudoscoring are its most significant advantages over the other current scales. An operative manual of the RLS85 in Portuguese is standardized in this text which also provides a selected bibliography on the subject. PMID- 8215917 TI - [Anatomical classification of anterior encephaloceles]. AB - The authors present an anatomical classification of the anterior encephaloceles. The importance of a topographic knowledge of such anomalies in their diagnosis and treatment is emphasized in order to avoid complications during the investigation of a cranio-facial protrusion. PMID- 8215918 TI - [Acute multiradiculopathy: report of 56 cases]. AB - The purpose of this report is to discuss the clinical characteristics, frequency and incidence of 56 cases of the Guillain-Barre syndrome studied during a nine years period (1982-1991). Results are discussed and main topics pointed out are: incidence of the syndrome at the withered part of the State of Alagoas, sex-age, and long-term risk factors for people living in this region. PMID- 8215919 TI - [Temporal lobectomy in cerebral infarction with mass effect]. AB - Cerebral edema secondary to ischemia can threaten life, mainly due to frequent failure of medical management. Imminent herniation of the temporal lobe can be timely detected by clinical signs and CT-scan. Eight patients (4M, 4F; 48-74 years, mean 62) with ischemic stroke and imminent herniation, were surgically decompressed by a standard temporal lobectomy as described by Olivier for temporal lobe epilepsy. Six patients survived, two died and were considered failure of the procedure, probably due to late surgical indication. In conclusion, temporal lobectomy is life-saving for patients with large ischemic cerebral infarction with mass effect and deteriorating signs of brain stem compression. PMID- 8215920 TI - Isolated and painless infraspinatus atrophy in top-level volleyball players. Report of two cases and review of the literature. AB - Isolated and painless infraspinatus atrophy and weakness are described in two top level volleyball players. EMG revealed isolated denervation of the infraspinatus muscle. One athlete continued playing and his clinical features have not changed. The other recovered her muscle bulk and strength after stopping playing. These findings were attributed to intense activity of the shoulder joint, without any direct trauma. On clinical grounds, we did not consider these cases as true examples of entrapment neuropathy. Pathogenesis was related to traction of the distal branch of the suprascapular nerve during the act of reception of the ball ("Manchete"). PMID- 8215921 TI - [Hallervorden-Spatz syndrome: report of a case]. AB - It is reported the case of a male patient with 19 years old presenting progressive behavior disturbance and dystonic posture beginning on right, with approximately five years of evolution. Extrapyramidal and pyramidal syndrome was evidenced at examination. This finding suggests Hallervorden-Spatz disease which was confirmed by resonance imaging (MRI). The purpose of reporting this case is to call attention for the importance of MRI in the study of degenerative diseases of the nervous system. PMID- 8215922 TI - Lymphocyte alveolitis in HAM/TSP patients. Preliminary report. AB - HTLV-I associated myelopathy has been described as a systemic disease characterized by manifestations in several organs outside the nervous system. We report inflammatory pulmonary involvement in patients with diagnosis of HAM. PMID- 8215923 TI - Considerations on HAM/TSP. Rediscovering Tumaco. AB - Considerations are made on the role of HTLV-I in the etiopathogeny of HAM/TSP. Neuroepidemiologic data reported in the literature are revisited for this purpose. Among results of this evaluation it is pointed-out that the Okinawan Community of Brazil presents ethnographic and demographic characteristics which are ideal for designing new studies. For instance, analyses on HTLV-I and on HAM/TSP in face of the cohort of such community classified according to time and direction of the migration (Japan-Brazil and vice-versa), will ensure promising results for the understanding of etipathogeny of HAM/TSP. They can also be paths towards clarifying the simultaneous generating, of geographical foci of the disease distant one the other, as that of Tumaco and that of south Japan. PMID- 8215924 TI - [In memoriam: Alexandre Alberto de Alencar (1929-1991)]. PMID- 8215925 TI - Cysticercosis of the central nervous system and cerebrospinal fluid. Immunodiagnosis of 1573 patients in 63 years (1929-1992). AB - Attention given to prophylaxis of neurocysticercosis (NC) is far beyond minimal needs among several regions of the in-development world, and for this reason incidence of the disease persists high among them. This investigation was carried out to show the extent of the problem by analysing the incidence of NC in a region of Brazil (Sao Paulo). CSF immunodiagnosis of NC by detecting antibodies to Cysticercus cellulosae in a neurodiagnostics laboratory is evaluated for this purpose. Cases studied in a 63-year period (1929-1992) are reviewed. Total cases in this period is 139,000, and for 1,573 (1.13%) diagnosis is NC. Special characteristics were not detected for colour and sex prevalence. Age bracket prevalence is from 21 to 40 years old (55.3%) high rates occurring for women between 21 to 30 years old, and for men between 31 to 40. Cases distribution in five consecutive decades (1942-1991) shows no decreasing tendency: average incidence is 1% for the 50 years, and it is over this average for the last three decades. Data confirm that incidence continues expressively high throughout the 50 years covered by this study. PMID- 8215926 TI - Machado-Joseph disease of Azorean ancestry in Brazil: the Catarina kindred. Neurological, neuroimaging, psychiatric and neuropsychological findings in the largest known family, the "Catarina" kindred. AB - At the moment 9 seemingly independent families with the clinical diagnosis of MJD are known in Brazil. The largest family tree of Azorean ancestry contains 622 individuals in 9 generations. 236 were examined, 39 found to be affected by two examiners. Phenotypes I, II and III were expressed by 12, 23 and 4 patients with age of onset by phenotypes being 10-48, 14-54 and 30-55 respectively. Although clinically more severe, juvenile onset type I disease did not show as severe a ponto-mesencephalic atrophy on MRI as the father with type II disease of similar symptomatic duration. None of the 8 patients examined with MRI showed olivary atrophy or pallidal abnormalities. 12 affected and 23 at risk were evaluated with neuropsychological tests. Attention was normal in both groups. Verbal memory scores were below normal in the affected and there was greater decay with time than in the risk group. Both scored below normal in identifying silluettes and constructional praxis. Visual memory scores were well below normal for both, with many rotations but no omissions or confabulations. A peculiar pattern of multiplying internal details called "the fly-eye effect" was observed in 6 affected and 8 at risk. Defective color distinction when multiple colors presented close to each other, in face of proper naming of individual colors ("color simulatanagnosia"), was looked for in 29 people. 4/10 affected and 4/19 at risk showed this phenomenon. Cognitive dysfunctions in this MJD family are prominent in the sphere of vision. Whether they constitute an early manifestation in those at risk and thus serve as a clinical identifier of the illness is yet to be established. Depression was looked for in the history of the family with DSM III-R criteria and an attempt at quantification with the Montgomery-Asberg Rating Scale. There was no significant quantitative difference between affected and at risk. Once undeniably symptomatic however, the patients had no, or less depression than themselves before or at the early stages of the illness. Covert depression was appropriately excluded. Fully established MJD in this family seemed to exert a protective effect from depression. PMID- 8215927 TI - [Prophylactic treatment of migraine: a prospective open study on 100 patients]. AB - The prophylactic value of a daily dose of 10 mg flunarizine, a calcium antagonist, was analysed in 100 migraineurs during 4-month in an open study. Ninety-three patients completed the full 16-week course of therapy, and seven patients presented important adverse reactions requiring discontinuation of the drug. However, the seven patients who dropped out during flunarizine treatment were not considered in the analysis. Side-effects included weight gain, sleepiness, humor depression, paresthesias and dry mouth. Eighty-one patients experienced abolition or significant reduction in headache incidence and/or severity. We conclude that flunarizine may be an effective drug in migraine prophylaxis. PMID- 8215928 TI - [Repetitive serum determinations of anticonvulsants in epileptic patients]. AB - To evaluate complacence in chronic epileptic women we collected weekly 144 blood samples from 38 patients for antiepileptic drugs determination. All the patients were supposed to have uncontrolled seizures using phenobarbital, phenytoin or carbamazepine monotherapeutically. We found that 34% of the blood levels were below the standard normal range. Blood level with great weekly variations were interpreted as inadequate intake by the patient. We conclude that repetitive antiepileptic blood levels determination may elucidate if the patient has drug resistant seizures or if the patient is not complacent to the drug therapy. PMID- 8215929 TI - Primary sleep enuresis in childhood. Polysomnographic evidences of sleep stage and time modulation. AB - The objective of this study was to evaluate enuretic events and its relations to sleep stages, sleep cycles and time durations in a selected group of children with primary essential sleep enuresis. We evaluated 18 patients with mean age of 8.2 years old (ranging from 5 to 12 years); 10 were males and 8 females (n.s.). They were referred to the Sleep Disorders Center with the specific complaint of enuresis since the first years of life (primary). Pediatric, urologic and neurologic workup did not show objective abnormalities (essential). The standard all-night polysomnography including an enuresis sensor attached to the shorts in the crotch area was performed. Only enuretic events nights were included. All were drug free patients for two weeks prior to polysomnography. In this report, only one polysomnography per patient was considered. The enuretic events were phase related, occurring predominantly in non-REM (NREM) sleep (p < 0.05). There was no predominance of enuretic events among the NREM stages (n.s.). A tendency of these events to occur in the first two sleep cycles was detected but may be due to the longer duration of these cycles. The events were time modulated, adjusted to a normal distribution with a mean of 213.4 min of recording time. PMID- 8215930 TI - [Hyperexcitability syndrome in the neonatal period: study of etiological factors]. AB - Forty-five newborn infants with hyperexcitability lasting more than 72 hours were studied in the neonatal period. The association with metabolic disturbances, mainly hypocalcemia, was observed in 53% of cases. Neonatal asphyxia was observed in 21 cases (46%), although all infants had 5 minutes Apgar scores above 6. Only 6 cases had association between neonatal asphyxia and metabolic disturbances. The hyperexcitability syndrome faded away in 1/3 of the infants with metabolic abnormalities after their correction. PMID- 8215931 TI - Neurological follow-up of small-for-gestational age newborn infants. A study of risk factors related to prognosis at one year of age. AB - To examine the relative importance of some risk factors and neurological prognosis in the first year of life, 37 small-for-gestational age newborns were followed prospectively to 1 year of conceptional age. An abnormal neurological examination was found in 51.3% of the newborns and, at 12 months, 32.5% were still considered abnormal. Only 8.1% of the group had severe neurological sequelae at 1 year of corrected age. The developmental tests showed little changes during the first year, with abnormality rates varying from 16.1 to 25%. The following risk factors were analyzed concerning their relation to neurological and developmental abnormalities: high-risk pregnancy, maternal hypertension, social class, pre-term birth, neonatal asphyxia and weight and height less than 2.5 percentile at the age of 1 year. The statistical analysis showed a high correlation between subnormal weight gain and neurological (p = 0.0001) and developmental (p = 0.001) abnormalities at 1 year. None of the other risk factors were statistically related to neurological prognosis at 1 year. PMID- 8215932 TI - [Epileptic encephalopathies in childhood]. AB - We present the study of 23 pediatric cases with infantile epileptic encephalopathies at the ambulatory neuropediatric facility of the Hospital Base Cayetano Heredia and ambulatory neurologic facility of Hospital IPPS Guillermo Almenara (Lima, Peru) between January 1984 and October 1988 with 6 to 54 months follow-up. There was one patient with Ohtahara syndrome, 9 with West syndrome and 13 with Lennox-Gastaut syndrome. The clinical and electroencephalographic characteristics were reviewed and related with the outcome. Despite the general characteristics of Ohtahara syndrome our patient had a good prognosis; only two West evolve into Lennox-Gastaut and none of these was West. Although the common features in these syndrome include frequent and intractable seizures and grave prognosis most of our patients had a good control of seizures. PMID- 8215933 TI - [Clobazam use in refractory epilepsies in children]. AB - We present the study of 20 pediatric patients with difficult controlled epilepsy in which we used clobazam as adjuvant anticonvulsant therapy between January 1986 and July 1990 at the outpatients neuropediatric facility of the Hospital General Base Cayetano Heredia and the private practice, with 6 to 45 months follow up. The mean age for the onset of the epilepsy was 22 months and the most frequent kind was the generalized epilepsy syndrome both secondary and idiopathic. It was obtained a significant decrease of seizures in 60% of the patients with a complete control in 35% of the total. It was found the best outcome in secondary generalized epilepsies Lennox-Gastaut and West types. It was found tolerance phenomenon in 25%, and psychotropic effect in three patients. We suggest the use of this 1,5 benzodiazepine drug in difficult controlled epilepsies in children of our region. PMID- 8215934 TI - [Bacterial meningitis in the neonatal period. Clinical evaluation and complications in 109 cases]. AB - Bacterial meningitis has special clinical features in the newborn infant. Major complications and sequelae result from the infectious involvement of the CNS in the majority of these children. We studied 109 newborn infants with bacterial meningitis accompanied from January 1977 to April 1987. The mortality rate was 34.8%. Perinatal risk factors were not found. The majority (80.5%) were term newborn infants. The main signs at admission were convulsion (53.2%), bulging fontanel (37.6%) and apnea (20.2%), and the main symptoms were neurosensorial depression (64.2%), nursing refuse (64.2%), fever (50.5%) and irritability (35.8%). Complications during hospitalization were ventriculitis (34.9%), inappropriate antidiuretic hormone secretion syndrome (27.5%), subdural collection (8.3%), brain abscess (4.6%) and brain infarction (2.8%). Inappropriate antidiuretic hormone secretion syndrome and ventriculitis were closely associated with high mortality. Seventy one children survived: 44 (62%) had gross abnormalities at the neurologic examination, and 29 (40.8%) developed hydrocephalus. Neurological follow-up of these children is important. Prognostic can change along the course of long time follow-up. PMID- 8215935 TI - Histopathological and immunohistochemical study of the brain and heart in the chronic cardiac form of Chagas' disease. AB - A histopathological and immunohistochemical study of the brain and heart was made in 50 patients with the chronic cardiac form of Chagas' disease. The immunohistochemical technique used was the peroxidase-antiperoxidase method adapted for the demonstration of the T. cruzi amastigotes. Histological and immunohistochemical examination of the brain showed encephalitis in multiple foci, although sparse, in four patients (8%). In one of the patients the process was recent, active, and containing parasites. In the other three patients, the lesions were of minor intensity, with light exudative inflammatory changes, suggesting a process becoming inactive, or already inactive. The search for parasites in these three patients was negative, even with use of immunoperoxidase. The heart histological and immunohistochemical study showed, besides the chronic myocarditis in multiple foci associated with interstitial fibrosis, amastigotes in seven patients (14%). The absence of parasites and of inflammatory changes in the brain in the great majority of patients with chronic Chagas' disease, contrasting with the constant finding of inflammatory changes and the occasional finding of amastigotes in the myocardium of the same patients, allows us to state, in the same way other authors did, that there is no histopathological basis to support the existence of the chronic nervous form of Chagas' disease. PMID- 8215936 TI - [Histoplasmosis of the central nervous system: study of cerebrospinal fluid in 8 patients]. AB - One hundred and thirteen samples of CSF from eight patients with chronic meningitis were studied in a 12 years period (September, 1980-August, 1992). None of them had AIDS. In all, CNS histoplasmosis diagnosis was made by CSF examination. All cases tested positive for antibodies to Histoplasma capsulatum in CSF; in one case the yeast grew in Sabouraud culture in three different occasions. The main findings in CSF by the time of the diagnosis were: moderate hypercytosis marked by lymphocytes and monocytes, neutrophils-being present and in some cases eosinophil cells; moderate increase of total proteins content; decrease in the glucose content; and moderate increase of gamma globulins sometimes with oligoclonal reaction. Patients were followed-up from 7 to 102 months, and periodically submitted to CSF examinations according to clinics. Cell number and total protein content of CSF showed marked episodes of exacerbation in the follow-up, with a dissociated profile favoring total protein content which got higher with the chronification of the disease. Changes in the CSF pattern with treatment were: rapid decrease of hypercytosis; disappearence of neutrophil and eosinophil cells; increase in glucose content; and slow reduction of the increased contents of total proteins and gamma globulins. PMID- 8215937 TI - [Surgical treatment of intracranial aneurysms: comparison between early and late surgery]. AB - The clinical course of patients with subarachnoid hemorrhage (SAH) due to rupture of cerebral aneurysm admitted during the last five years is analysed: 157 patients were treated by direct surgical approach of the aneurysm, 58 localized in the anterior communicating artery (ACoA), 48 in the internal carotid artery (ICA), 43 in the middle cerebral artery (MCA), and 8 in the posterior circulation. Fourty-four patients were operated on during the first 72 hours (early surgery), 40 during the 4th and 7th days, 16 during the 8th and the 10th, and 57 after the 10th (late surgery). According to main localizations, the outcome of patients with aneurysms in the ACoA was good in 79.1%, in the ICA in 69.7%, and in the MCA in 69.7%. Patients treated in Hunt & Hess grade I and II had both good results in 77.5%, grade III patients had good results in 71.3%, and grade IV in 56.2%. According to timing of surgery good results were observed in 61.4% for patients submitted to early surgery, in 80% for patients treated during the 4th and 7th days, in 81.2% for patients treated during the 8th and the 10th days, and in 70.2% for that submitted to late surgery. The overall mortality was 14.6%. For grade I patients mortality was 6.4%, for grade II was 12.2%, for grade III was 15.2%, for grade IV was 25%, and all patients operated on in grade V died.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215938 TI - [Lipomyelomeningocele: experience with 16 operated cases]. AB - Sixteen patients with lipomyelomeningoceles were operated by microsurgery technics from 1980 to 1991. Patients with lipomyelomeningoceles inappropriately treated or not submitted to treatment will develop significant neurological sequelae. In the authors' opinion, proper management of the patient with spinal lipoma requires early prophylactic resection of the lipoma and untethering of the spinal cord. PMID- 8215939 TI - Peracetic acid and its application to medical instrument sterilization. AB - Peracetic acid is recognized as a powerful germicidal agent. However, heretofore its corrosive nature has prevented its direct use for medical instrument sterilization. A specially formulated buffered peracetic acid sterilant with anticorrosives has been developed for use in the STERIS PROCESS. The STERIS SYSTEM 1 Processor and the STERIS 20 Sterilant Concentrate have met or exceed the rigorous requirements of the Environmental Protection Agency and Food and Drug Administration for making claims related to sterilization. With this system, medical devices including endoscopes are sterilized and ready for use in less than 30 min. PMID- 8215940 TI - Renal effects of multiple infusion of pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP) solution in dogs. AB - Pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP), which is made from out dated human red blood cells by two major chemical modifications, namely pyridoxalation and conjugation with polyoxyethylene (POE), is currently under development as a physiological oxygen carrier. This study assessed the effects of PHP-88 solution, which contains 8% (wt/vol) each of hemoglobin (Hb) and maltose, on renal function when it was infused 3 times every other day into the intact circulation of 8 dogs (5 dogs for the PHP group and 3 for the control group; 20 ml/kg for the first infusion, and 10 ml/kg each for the second and third infusions, at the rate of 2.5 ml/h/kg). Serial determinations of glomerular filtration rate (GFR) and renal plasma flow (RPF) were carried out pre- and postinfusion for up to 3 months along with measurements of blood and urine analyses, urine output rate, fractional excretion of sodium (FES), and free water clearance (CH2O). The results showed that plasma colloid osmotic pressure (COP) elevated an average of 3.3 mm Hg (p = 0.0085), and GFR and RPF tended to increase by 13% (NS) and 38% (NS), respectively, immediately after the third infusion with PHP solution. Urine output rate increased during and after the infusion, and FES and CH2O also increased for 24 h after the infusion in both groups. Blood urea nitrogen, serum creatinine, and serum Na+ concentrations were not affected greatly by the infusions, but hematocrit was decreased by 8% in the PHP group, indicating approximately a 42% expansion of plasma volume. These changes were observed to return to their preinfusion levels by 1 week postinfusion. Renal histology of the PHP group obtained at 2 weeks postinfusion revealed vacuole formation in the proximal tubules which was not associated with any pathologic changes indicative of cell death or regeneration. In 4 out of 5 dogs at 3 months postinfusion (necropsy), the vacuoles were not present. Though urinary N-acetyl beta-glucosaminidase (NAG) activity had significantly increased after infusion, it returned to the preinfusion level by 1 month postinfusion. No detrimental effect of vacuoles on the assessed renal tubular functions was confirmed in the present study. The results demonstrated that multiple infusions of PHP solutions were well tolerated in normal dogs, and the observed effects were conceived predominantly attributable to the physiological response of the kidneys to an oncotic load into the circulation, which produced plasma volume expansion. PMID- 8215941 TI - Mechanical blood traumatization by tubing and throttles in in vitro pump tests: experimental results and implications for hemolysis theory. AB - Blood has become essential as a test fluid to evaluate hemolysis and biocompatibility of blood pumps in vitro. The blood is usually pumped from a blood bag into a circuit against elevated pressure. A throttle or a length of tubing is used to produce the pressure head. Blood damage caused by the shear stress in these pressure-reducing devices should be minimal. It is not known whether the high but short-lasting shear stress in a throttle is more or less damaging to the blood than the low but long-lasting stress in tubing. In this study, throttles (width 11 mm, minimal height 0.9 mm, length 30 mm; shear stress = 136 N/m2 lasting for 3.23 ms); and tubing (inner diameter 9.5 mm, length 4.5 m, shear stress = 4.5 N/m2 lasting for 3.5 s) were compared at a flow of 5 L/min and a pressure drop of 150 mm Hg. Experiments (n = 10) with bovine blood were performed in two parallel setups using Bio-Medicus pumps BP80. Free hemoglobin in plasma (fHb) and thromboxane B2 (TXB2) were measured. After 6 h, the fHb increase was 31.9 +/- 19.1 mg% for the throttle setup and 32.3 +/- 16.2 for the tubing setup. The TXB2 release was 296 +/- 70 and 305 +/- 54 pg/0.1 ml respectively after 4 h. In summary, no significant differences between the two setups for either fHb or TXB2 could be detected. So the use of a throttle, which requires far less priming volume and a smaller blood-contacting surface while also offering a wider range of adjustment, seems preferable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215942 TI - A novel electromechanical drive for a tether-free implantable ventricular assist device. AB - A tether-free ventricular assist device (VAD) based on a novel electromechanical drive was prototyped and evaluated. The unit can be adapted for implantation. The device utilizes a bladder-type ventricle taken from a pneumatically driven VAD. In mock loop testing, the unit has met the design capacity of 6 L/min against a pressure head of 150 mm Hg. The efficiency of the device allows it to operate at design flow and pressure for periods of up to 8 h when powered by a single rechargeable battery pack weighing less than 5 kg. The mechanism consists of a seamless sac-type bladder situated between hinged plates actuated by a motor driven bell-and-crank linkage. Cycle parameters are controlled by a microprocessor-based servomotor drive. PMID- 8215943 TI - Left and right pump output control in one-piece electromechanical total artificial heart. AB - Left master alternate (LMA) ejection control based on the left pump fill method was implemented for a one-piece electromechanical total artificial heart (TAH). The TAH consists of left and right pusher-plate-type blood pumps sandwiching a compact electromechanical actuator comprising a direct current (DC) brushless motor and a planetary roller screw. The motor rotation is controlled on the basis of the roller-screw position as detected by a Hall effect sensor and a commutation pulse counting method. Since the pusher-plate shaft and roller screw are decoupled during filling, both pumps fill passively with the right and left atrial pressure. To obtain response to the right atrial pressure change in the LMA mode, the left fill trigger level as detected by a Hall effect position sensor is adjusted to operate the pump at a higher rate and to drive the right pump at 85-90% of the full stroke level. The in vitro evaluation demonstrated that this method can respond to right atrial pressure changes provided that the right pump is operated at less than the full stroke level. When the preload is high and the right pump goes into full stroke operation, the left eject level can be decreased to run the pump at a higher rate and to transfer more blood from the right to the left. In the in vivo evaluation, which lasted 1 week in a 95 kg calf, the left and right atrial pressures were kept within physiological ranges.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215944 TI - Effect of blood access on the platelets of azotemic patients initiating dialysis therapy. AB - The effect of blood access on platelets and clotting factors was investigated in 46 azotemic patients. Arteriovenous fistula was used in 10 patients (AVF group), and polyurethane double-lumen catheters were inserted through the subclavian vein in 6 patients (PUS group) or through the femoral vein in 15 patients (PUF group). Indwelling urokinase-immobilized single-lumen catheters and double-lumen catheters were placed in the femoral vein of 5 patients (UKS group) and 10 patients (UKD group), respectively. Blood cell counts, beta-thromboglobulin (beta TG), platelet factor 4 (PF4), prothrombin time, and activated partial thromboplastin time were measured before insertion while catheters were indwelling and after catheters were pulled out. Although the platelet count decreased to 83% of the initial value during indwelling in the PUF group and 89% in the PUS group, it did not decrease in the AVF, UKS, and UKD groups. There were no differences between the PUF and PUS groups nor between the UKS and UKD groups. Plasma beta-TG increased in the PUF and UKD groups with indwelling catheters but did not change with the AVF. From these results, we conclude that the AVF did not activate platelets, the urokinase-immobilized catheter activated platelets, and the polyurethane catheter activated and decreased platelets. This might be due to the different surface properties of each blood access. Thus, the urokinase immobilized catheter seems to be more favorable than the polyurethane catheter for emergency blood access. PMID- 8215945 TI - Acetate-free biofiltration in acute renal failure. AB - Hemodialysis treatment for acute renal failure is associated with a high incidence of adverse reactions. Hemodynamic stability and adequate correction of acid-base and hydroelectrolyte imbalance are the main goals of dialytic strategy in acute renal failure. However, the variety of etiology and the diversity of clinical conditions suggest that individualized treatment may be advisable. To this purpose, in 26 patients suffering from "isolated" acute renal failure of different etiologies, we have used acetate-free biofiltration. We have performed 411 dialyses with an extremely low incidence of symptomatic treatments and remarkable cardiovascular stability. Correction of fluid, electrolyte, and acid base imbalance proved excellent. Dialytic efficacy proved adequate. Our data show that acetate-free biofiltration is an easy technique suitable for individualized treatment and adaptable to changing needs during hemodialysis in patients with isolated acute renal failure. PMID- 8215946 TI - No government overregulation on the development of new medical devices. PMID- 8215947 TI - Cardiopulmonary bypass: a historical perspective. AB - Cardiopulmonary bypass in the clinical setting is barely 40 years old. Yet worldwide, it is used in the operating room in more than 500,000 cases a year. This broad acceptance is a tribute to the vision of gifted investigators who could see beyond the mere technical problems of perfused isolated organs. They integrated mechanical concepts, knowledge of materials, and sheer inventiveness with an appreciation of physiological issues to address the clinical needs of open-heart surgery. PMID- 8215948 TI - Chronic biofiltration therapy. AB - Long-term follow-up evaluation of biofiltration treatment in 7 patients is presented. These patients experienced frequent episodes of hypotension during acetate hemodialysis. A 3-year biofiltration treatment reduced by 43% episodes of symptomatic hypotension and produced a significant increase in the pretreatment pH and plasma bicarbonate levels. The beta 2-microglobulin level was significantly reduced during biofiltration therapy. The mean systolic and diastolic blood pressures slightly increased during biofiltration. Uremic polyneuropathy, as demonstrated by an increase in motor nerve conduction velocity, slightly improved. The patients reported increased comfort during biofiltration therapy. PMID- 8215949 TI - Continuous on-line optical absorbance recording of blood volume changes during hemodialysis. AB - Conventional techniques that measure blood volume changes during hemodialysis are invasive, hard to reproduce, and provide only intermittent evaluations. To overcome these drawbacks, we have developed an optoelectronic instrument that estimates intradialytic blood volume percentage changes by the optical absorbance of blood. This device is based on the absorption of light transmitted through blood, which is directly related to the hemoglobin concentration. A personal computer interfaced to the device provides a continuous on-line graphic display of the hemoglobin levels and the percentage changes in blood volume. The noninvasive measurement of dialysis blood volume changes by an optical method may be helpful in detecting the appearance of severe hypovolemia that can be dangerous in critically ill patients. PMID- 8215950 TI - Renal complications of infected ventriculoatrial shunts. AB - Contamination of a ventriculoatrial shunt (VAS) with skin organisms that are usually nonpathogenic may be followed by an immunologically mediated renal injury. The bacteria characteristically involved are coagulase-negative Staphylococci (e.g., Staphylococcus epidermidis), which strongly adhere to the plastic surface of the VAS. These bacteria are protected from the body's natural defense mechanisms and respond only poorly to antibiotics. As a result, their growth persists and produces a continuous antigenic stimulation. Circulating immune complexes (CIC) are an appropriate tool to screen for chronically infected VASs. We followed CIC in 138 VAS patients. An infected VAS was seen in 20 of the 24 patients with highly elevated CIC and in 1 of the 19 patients with moderately elevated CIC, but none of the 95 patients with normal CIC had evidence of shunt infection. Of the 21 patients with shunt infections, 8 had renal involvement (4 requiring dialysis, and 4 with proteinuria, hematuria, and/or elevated creatinine). Results from kidney biopsy specimens available from 4 patients confirmed glomerulonephritis. Of the 4 patients requiring dialysis at diagnosis, renal function recovered sufficiently to stop dialysis after successful VAS exchange in all but 1. In the other 4 patients, renal symptoms (proteinuria, creatinine) also improved after VAS revision. Chronic infection with S. epidermidis or other bacteria is a continuing problem in patients with VASs and can lead to an immune-mediated renal injury. However, the prognosis for reversal of the renal injury is relatively good if the VAS infection is treated promptly. PMID- 8215951 TI - Pretransplantation immunoadsorption therapy in patients immunized with human lymphocyte antigen: effect of treatment and three years' clinical follow-up of grafts. AB - Sensitization against human lymphocyte antigen (HLA) occurs frequently in previously transplanted patients that lose a first cadaveric graft. To shorten their time on the waiting list and reduce the incidence of early rejection in such patients, we performed immunoadsorption therapy by a tryptophan column in 10 patients as an attempt to remove circulating antibodies prior to regrafting. Resynthesis of antibodies was suppressed with cyclophosphamide and prednisolone. Following the course of immunoadsorption therapy, the panel reactive antibodies (PRA) decreased by more than 50% from the pretreatment values. In the present study, 8 patients were transplanted with cadaveric renal grafts. At the time of follow-up, graft survival was 63% in these patients (2-36 months post transplantation, mean 23 months). There was one incidence of acute rejection, one graft was lost within 48 h owing to renal artery thrombosis, and one was lost within 2 weeks as a result of stenosis. The serum creatinine levels were down to near normal during the first 3 weeks in hospital (p < 0.0001) and remained at this level during the period of follow-up. We conclude that immunoadsorption might be a beneficial pretransplantation therapy and an alternative to plasmapheresis in HLA-immunized patients awaiting kidney transplantation. PMID- 8215952 TI - Continuous hematocrit monitoring method in an extracorporeal circulation system and its application for automatic control of blood volume during artificial kidney treatment. AB - A two-frequency electrical conductivity method for measuring hematocrit has been developed for use in the continuous monitoring of circulating blood volume during artificial kidney treatment. Using this method, an algorithm for programmed control of blood volume also has been developed. This hematocrit measurement method is based on the beta-dispersion of blood conductivity, and the values measured during hemodialysis are in good agreement with the laboratory hematocrit values obtained by a Coulter counter. Programmed control of blood volume was used 29 times on 11 patients undergoing long-term dialysis. In each case, the blood volume was maintained within 2.5% of the desired level, and stable control was achieved even with disturbances caused by eating, change in body position, and so on. These methods can be used to study the relationship between blood volume and dialysis-induced hypotension during artificial kidney treatment and to achieve adequate ultrafiltration without clinical adverse effects. PMID- 8215953 TI - Anticoagulation with low molecular weight heparin (Fragmin) during continuous hemodialysis in the intensive care unit. AB - A preparation of low molecular weight heparin (Fragmin) was administered to patients with multiorgan failure receiving continuous venovenous hemodialysis. Three patients received a high-dose regimen (35 IU/kg bolus followed by 13 IU/kg infusion), and 7 received a low-dose regimen (8 and 5 IU/kg, respectively) for 36 h. High-dose Fragmin was associated with minimal clotting in the extracorporeal circuit. Plasma fibrinopeptide A levels declined, and mean anti-Xa activity was in the range 0.47-0.79 IU/ml. The urea equilibration coefficient (UEC) (100% at initiation) remained above 90% throughout. All 3 patients had mild bleeding episodes, which led to discontinuation of Fragmin in 1. During all low-dose treatments, marked thrombus formation occurred in the extracorporeal circuit, and in 2, the circuit clotted within the study period. Fibrinopeptide A levels further increased in 4 patients, and mean anti-Xa activity was in the range 0.27 0.53 IU/ml. UEC declined appreciably in 3 treatments (including the 2 in which early circuit clotting occurred). One patient experienced a mild bleeding episode. The low-dose Fragmin regimen produced safer anticoagulation in patients at risk from bleeding and is suitable for prolonged renal support although the tendency to thrombosis may necessitate more frequent circuit changes. PMID- 8215954 TI - Effect of surface-immobilized heparin on the activation of adsorbed factor XII. AB - Two different heparin surfaces, structurally closely related and of similar negative charge characteristics, were compared with regard to adsorption and activation of coagulation Factor XII (FXII). One surface was prepared by immobilization of unfractioned heparin, which yielded a surface containing both heparin molecules with high and with low affinity for antithrombin (unfractioned [UF] heparin surface). The other surface consisted of a fraction of heparin molecules with low affinity for antithrombin (LA heparin surface) and essentially devoid of antithrombin-binding as well as anticoagulant activity. Both surfaces adsorbed FXII from plasma to a similar extent, and essentially the same quantities of bound factor could be recovered from the surfaces. The two heparin surfaces, however, differed markedly with regard to activation of the adsorbed FXII. On the LA heparin surface, a major portion of the surface-bound FXII was recovered in its enzymatically active form (FXIIa), but only trace amounts of the FXII taken up by the UF heparin surface had undergone activation. When FXII deficient plasma was used instead of normal plasma, no surface-associated enzyme activity could be recovered on either surface. The presence of free standard heparin or low molecular weight heparin in the plasma exposed to the LA heparin surface did not prevent conversion of FXII to FXIIa. PMID- 8215955 TI - Porcine pancreatic islets: isolation, microencapsulation, and xenotransplantation. AB - To provide a plentiful source of pancreatic islets for future clinical transplants into diabetic patients, we have developed a simple and reliable method to isolate porcine islets of a high degree of purity. Porcine pancreata were perfused and digested with collagenase, and the islets were then purified on dextran density gradients. In order to avoid any damage to the islets, no mechanical devices nor any strenuous treatment was employed. As many as 5 x 10(5) islets were isolated from a single porcine pancreas. Islets were encapsulated in alginate-polylysine-alginate membranes with the aid of an electrostatic droplet generator. In vitro studies demonstrated that the isolated islets secreted insulin in response to glucose and 3-isobutyl-L-methylxanthine (IBMX) challenge for at least 4 weeks. Perifusion studies showed that the kinetics of insulin release from the encapsulated islets was similar to that exhibited by free islets. In in vivo studies, 18 diabetic BALB-c mice were transplanted with 1,500 2,500 encapsulated islets each. In 13 recipients, the diabetic condition was reversed for at least 85 days. When capsules were removed from 2 transplant recipients, their diabetic condition quickly recurred. PMID- 8215956 TI - The significance and prevention of air emboli with the total artificial heart. AB - Embolism remains a significant complication of the total artificial heart (TAH). The ineffectual deairing of the TAH can allow embolization of the retained air. The standard needle aspiration of TAH air (Group A) was compared with a new protocol (Group B) that included standard needle TAH aspiration plus simultaneous pumping of the TAH against an occluded ascending aorta and main pulmonary artery with vacuum applied to a needle in the proximal aorta and pulmonary artery. There were 4 calves in each group. There was no premortem evidence of systemic or pulmonary emboli. Both groups of animals were electively terminated less than 2 weeks postoperatively Postoperative mean aortic and pulmonary artery pressures were recorded for each animal. Animals in Group B had a significant decline in pulmonary artery pressures (43 +/- 12 vs. 33 +/- 8 mm Hg) 1 h after TAH implantation when compared with Group A. All other aortic and pulmonary artery pressure differences between Groups A and B were not statistically significant within 24 h of the operation. Group A animals had a 75% incidence, and Group B animals had 100% incidence of TAH thrombus. This very small thrombus was found exclusively at the inflow valve-TAH housing interface. Evaluation of the kidneys postmortem was used to identify embolic injury. All animals in Group A had evidence of acute, hemorrhagic injury, but none of the Group B animals had similar injury. Half of the animals in each group had small, fibrotic chronic renal cortical injury, which did not develop during TAH implantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215957 TI - Biological breakthroughs of relevance to continuing education. PMID- 8215958 TI - Definitions and classification of tic disorders. The Tourette Syndrome Classification Study Group. AB - Tics are brief movements (motor tics) or sounds (vocal tics) that occur intermittently and unpredictably out of a background of normal motor activity. Although tics can appear as the result of direct brain injury (so-called symptomatic, eg, from head trauma or encephalitis), they most commonly are idiopathic and are part of the spectrum of Gilles de la Tourette syndrome or other idiopathic tic disorders. To aid investigators searching for the gene(s) causing Tourette syndrome, criteria are proposed to classify the idiopathic tic disorders. Although some of these separate entities may ultimately be shown to be caused by the same gene, until that is established, it is considered best when searching for the Tourette's gene to have tic disorders classified into distinct, homogeneous entities. The proposed classification will likely change over time as better diagnostic techniques become available and can both expand and consolidate, particularly after the Tourette gene is located. PMID- 8215959 TI - The association of multiple personality and temporolimbic epilepsy. Intracarotid amobarbital test observations. AB - OBJECTIVE: What is the relationship of "multiple personality disorder" in patients with temporolimbic epilepsy to certain types of hemispheric interaction? DESIGN: Case series. SETTING: Tertiary care referral center. PATIENTS: Two patients with temporolimbic epilepsy considered to be surgical candidates referred for the intracarotid amobarbital sodium procedure (IAP). Each individual had presented with different "personalities" in a characteristic temporal relationship to their seizures. INTERVENTIONS: Intracarotid amobarbital sodium procedure, Wada test, and electroencephalogram. MAIN OUTCOME MEASURES: Behavioral observations made during the performance of the IAP. RESULTS: During the IAP, each patient's peri-ictal "personality" changes were precisely replicated. No seizure activity was noted during the IAPs. CONCLUSIONS: These observations suggest that the association of multiple personality and temporolimbic epilepsy is not dependent on seizure discharges per se, but rather may be related to certain types of hemispheric interaction. PMID- 8215960 TI - The neurologic syndrome of severe Alzheimer's disease. Relationship to functional decline. AB - OBJECTIVE: To assess the possible association between functional decline and noncognitive neurologic signs in the severe stages of Alzheimer's disease (AD). DESIGN: Case series. SETTING: Subjects from a dementia research referral center, longitudinally followed, when necessary, into residential home and nursing home settings. PATIENTS: A consecutive sample of 56 patients (16 men, 40 women; mean age, 74.6 years) with a clinical diagnosis of probable AD in the moderately severe and severe stages. MAIN OUTCOME MEASURE: For global dementia severity, the Global Deterioration Scale and Mini-Mental State examination; for functional assessment, the Functional Assessment Staging Scale; and for assessment of neurologic function, nine release signs (primitive reflexes), 10 measures of extrapyramidal function, and five measures of pyramidal function, including deep tendon reflexes and plantar signs. Changes in activity or presence of neurologic signs were rated on a seven-point scale. Results were analyzed in terms of prevalence and magnitude of change in relation to functional impairment. RESULTS: Prevalence and mean scores of certain release signs, certain extrapyramidal measures commonly referred to as bradykinesia, and certain pyramidal signs showed significant associations with the magnitude of functional impairment. Other neurologic measures, for example, the palmomental reflex, and certain extrapyramidal measures commonly seen in Parkinson's disease, including the glabellar blink reflex, cogwheeling, tremor, shuffling gait, and festination, did not show significant increments with continuing functional decline in AD. CONCLUSIONS: Functional decline in the advanced stages of AD appears to be associated with a particular combination of progressive cortical, extrapyramidal, and pyramidal system dysfunction. The characteristics of this neurologic syndrome of the severe stages of AD differ from those of other neurologic disorders. For example, the pattern of extrapyramidal system disease is different from that seen in Parkinson's disease. The neurologic syndrome of the severe stages of AD is amenable to description and deserves further investigation. PMID- 8215962 TI - Topical aspirin in chloroform and the relief of pain due to herpes zoster and postherpetic neuralgia. AB - OBJECTIVE: To determine pain patterns and relationships in patients with herpes zoster and postherpetic neuralgia before and after topical application of aspirin dissolved in chloroform applied to the painful skin surface. DESIGN: A consecutive series of 42 patients examined and treated in a uniform manner and followed up until their pain subsided or this management mode failed. SETTING: An ambulatory referral private practice. PATIENTS: All patients had pain due to herpes zoster or postherpetic neuralgia and were referred for management of severe pain. None refused. INTERVENTION: Topical application of crushed aspirin tablets dissolved in chloroform. OUTCOME MEASURES: Short-Form McGill Pain Questionnaire. RESULTS: All patients reported substantially decreased pain promptly after treatment, with maximum relief at 20 to 30 minutes and lasting 2 to 4 hours. Patients gradually decreased the use of aspirin in chloroform as pain abated. CONCLUSIONS: Topical aspirin dissolved in chloroform is an effective means of reducing pain due to herpes zoster and postherpetic neuralgia in most patients. The locus of pain origin and analgesia induced by topical aspirin is most likely at cutaneous free-nerve ending pain receptors. The mechanism responsible for the analgesic properties of aspirin is probably not the same as that responsible for its anti-inflammatory properties. PMID- 8215961 TI - Comparison of cognitive changes in patients with Alzheimer's and Parkinson's disease. AB - OBJECTIVE: To compare cognitive changes in the dementias of Parkinson's disease (PD) and Alzheimer's disease (AD). DESIGN: Case series, group comparisons. SETTING: Ambulatory care referral center. PATIENTS: Consecutive sample of 14 patients with PD dementia and 27 with probable AD matched for overall intellectual function using a mental status test, as well as 14 non-demented PD and 12 mild probable AD patients, similarly matched for overall intellectual function. All demented patients met Diagnostic and Statistical Manual, Revised Third Edition, criteria for dementia. MAIN OUTCOME MEASURES: Performance on a battery of neuropsychological tests assessing verbal and nonverbal memory, verbal fluency, and constructional ability. RESULTS: Nondemented and demented patients with PD performed worse than their probable AD comparison groups on verbal fluency and visuospatial tasks. Cognitive changes attributable to dementia were similar in PD and probable AD but were not identical. The patients with probable AD demonstrated more marked change in memory performance with delay. CONCLUSIONS: Our findings suggest that when dementia occurs in PD it is overlaid on cognitive changes that already exist in nondemented patients but that the dementing process in PD involves systems other than those responsible for cognitive change in nondemented PD patients. We hypothesize that in most cases, dementia in PD involves changes in a nondopaminergic neurotransmitter system but is not due to concomitant AD. PMID- 8215963 TI - Increased levels of truncated nerve growth factor receptor in urine of mildly demented patients with Alzheimer's disease. AB - OBJECTIVE: In Alzheimer's disease, cholinergic basal forebrain neurons, which have receptors for nerve growth factor (NGF), degenerate, while NGF receptors increase in some areas of the neocortex. Levels of the truncated, extracellular portion of the NGF receptor (NGF-Rt) are elevated in urine of patients with peripheral neuropathies and in animals with peripheral-nerve injury, but it has not been determined whether urine levels of NGF-Rt are altered by the presence and/or progression of dementia-related neuropathologic changes in patients with Alzheimer's disease. In this study, we developed an enzyme-linked immunosorbent assay to determine whether urine levels of NGF-Rt are altered in patients with Alzheimer's disease. DESIGN: Survey of urine NGF-Rt levels in neurologically normal (n = 19), mildly demented (n = 31), and moderately to severely demented (n = 31) patients. SETTING: Subjects were participants in the Rochester Alzheimer's Disease Project and mildly demented patients about to begin a clinical drug study. PATIENTS: All patients met established criteria for a clinical diagnosis of probable Alzheimer's disease. Aged, nondemented, neurologically normal controls were selected from the families of the demented subjects. RESULTS: Urine NGF-Rt levels were substantially elevated in mildly demented patients relative to those of nondemented controls. CONCLUSIONS: These results suggest that an enzyme linked immunosorbent assay on urine samples may provide an antemortem measure of dementia-related neuropathologic changes, but further study is needed to determine the source and potential clinical utility of increased NGF-Rt levels in urine of mildly demented patients. PMID- 8215964 TI - Weeping as a common element of pseudoseizures. AB - Weeping is an extremely rare ictal phenomenon. We report weeping during or at the very end of electrographically proved pseudoseizures in 10 patients. We conclude that weeping is a relatively common and specific clinical feature of pseudoepileptic seizures. PMID- 8215965 TI - Decreased nociceptive flexion reflex threshold in chronic tension-type headache. AB - OBJECTIVE: To study nociceptive processing in chronic tension-type headache. DESIGN: Survey of the threshold for the nociceptive flexion reflex obtained by sural nerve stimulation in a convenience sample of 40 patients with chronic tension-type headache and in 29 sex- and age-matched healthy subjects. Muscular response was recorded from the biceps femoris muscle. For each stimulation, subjects recorded pain on a visual analogue scale. RESULTS: In seven subjects (four headache sufferers and three healthy subjects), no nociceptive flexion reflex response could be elicited. The median nociceptive flexion reflex threshold in the headache group was significantly lower (median, 10 mA) than in the control group (median, 20 mA). Pain tolerance thresholds were significantly lower in the headache group than in the control group. A high degree of correlation was found between nociceptive flexion reflex threshold and tolerated stimulus strength. The slopes of the stimulus intensity/visual analogue scale pain rating response curves were steeper in patients with headache than in control subjects. CONCLUSIONS: Chronic tension-type headache may represent a disorder of an endogenous antinociceptive system with a lowering of tone and recruitment of descending inhibitory systems. PMID- 8215966 TI - Callosal atrophy parallels decreased cortical oxygen metabolism and neuropsychological impairment in Alzheimer's disease. AB - OBJECTIVE: To evaluate the relationship of corpus callosum atrophy to cerebral cortical oxygen metabolism and cognitive function in patients with Alzheimer's disease. DESIGN: Prospective clinicoradiologic correlation with magnetic resonance imaging and positron emission tomography. SETTING: A university hospital. PATIENTS, PARTICIPANTS: Ten right-handed male patients with Alzheimer's disease, aged 46 to 70 years (mean +/- SD 57 +/- 6 years), and 14 age- and sex matched right-handed control subjects. MAIN OUTCOME MEASURES: The midsagittal corpus callosum areas (on T1-weighted magnetic resonance images), cerebral metabolic rate of oxygen (measured with positron emission tomography using the oxygen-15 steady-state technique), and the IQs of the Wechsler Adult Intelligence Scale. RESULTS: Compared with control subjects, the patients had significantly decreased callosal areas with a posterior predominance of the degree of atrophy. The area of anterior and posterior halves of the corpus callosum had a significant correlation with the value of oxygen metabolism in the frontal and parietotemporo-occipital association cortices, respectively. The total area of the corpus callosum was significantly related to the total and verbal IQs of the Wechsler Adult Intelligence Scale. CONCLUSION: Atrophy of corpus callosum reflects the severity and pattern of cortical damage associated with hypometabolism and cognitive impairment in Alzheimer's disease. PMID- 8215967 TI - Functional and magnetic resonance imaging correlates of callosal involvement in multiple sclerosis. AB - To investigate functional and anatomical features of callosal involvement in multiple sclerosis (MS), performances of 90 patients with definite MS and 25 matched normal control subjects were compared on three tasks exploring interhemispheric transfer of auditory, sensory, and motor information: a verbal dichotic listening task, a crossed tactile finger localization task, and an alternate finger tapping task. Each patient also underwent a magnetic resonance imaging (MRI) scan (1) to appreciate the extent of white-matter changes by a semiquantitative evaluation of hemispheric brain MRI hyperintensities and (2) to measure the degree of total and regional callosal atrophy using an automatized method of partition of the midsagittal callosal area. Interhemispheric transfer and/or integration was impaired in patients with MS for all modalities explored and proportional to both degree of callosal atrophy and diffusion of white-matter lesions. Moreover, in good agreement with data obtained from partial commissurotomy studies, performance on each functional task was predominantly associated with atrophy of one part of the callosum, namely left-ear dichotic suppression with the posterior callosal region, alternate finger tapping with the anterior region, and cross-localization with midanterior and posterior regions. Finally, a subgroup of patients without MRI white-matter hyperintensities also showed significant impairment of callosal function and relative atrophy of the callosum. These findings suggest the potential clinical value of callosal involvement in MS and the usefulness of MS as a model of interhemispheric disconnection. PMID- 8215968 TI - Vascular amyloid deposition in Alzheimer's disease. Neither necessary nor sufficient for the local formation of plaques or tangles. AB - OBJECTIVE: To determine the relationship between vascular beta-amyloid (beta A4) and senile plaques (SPs) and neurofibrillary tangles (NFTs). DESIGN: We counted vascular amyloid deposition with SP and NFT density in the medial temporal lobe (CA1 plus the subiculum) and the cerebellum. PATIENTS: The brains of seven patients with Alzheimer's disease and of three age-matched nondemented control subjects were studied. RESULTS: In Alzheimer's disease, the density of beta A4 laden blood vessels was significantly higher in the cerebellum than in CA1 plus the subiculum. Conversely, the densities of SPs and NFTs were much greater in the CA1 plus the subiculum than in the cerebellum. CONCLUSIONS: This study indicates that local vascular beta A4 deposition is not directly correlated with SP and NFT densities. Deposition of beta A4 in blood vessel walls may not be instrumental in the formation of SPs and/or NFTs in the brain. PMID- 8215969 TI - Schizophrenia as a brain disease. The dopamine receptor story. PMID- 8215970 TI - Schizophrenia as a brain disease. PMID- 8215971 TI - How Twin Cities neurologists treat ischemic stroke. Policies and trends. AB - OBJECTIVE: To examine community practices. DESIGN: Physician practice policies were surveyed using case vignettes in which evaluation for carotid endarterectomy or use of anticoagulation therapy was at issue. Virtually the same group was surveyed in 1988 and again in 1991, after publication of carotid endarterectomy trials in symptomatic patients. SETTING: Greater Metropolitan Minneapolis-St. Paul, Minnesota. PARTICIPANTS: Community and academic neurologists in practice of general adult neurology. MEASUREMENT: Percentage of respondents who would recommend the management option in question for each vignette. RESULTS: Ninety eight percent favored evaluation for carotid endarterectomy in appropriately symptomatic "good risk" patients in 1988 before proof of efficacy became available. Proof increased the percentage (from 67% to 92%) favoring evaluation in older, sicker, symptomatic patients but not the percentage of those favoring evaluation of bruit patients (1988: 33%; 1991: 24%). In 1991, a lower percentage recommended warfarin therapy after noncardioembolic transient ischemic attack; this was especially apparent in the vertebrobasilar case (1988: 59%; 1991: 37%). Both years, nine of 10 neurologists recommended heparin therapy for progressing stroke, while half to three-fourths used it after partial stroke or transient ischemic attack. Almost all would use anticoagulants for secondary prophylaxis after suspected cardioembolic stroke. CONCLUSION: The results reflect a treatment oriented empirical approach in this community and document quick clinical application of scientific evidence when it became available. PMID- 8215972 TI - Ifosfamide-induced nonconvulsive status epilepticus. AB - We report the first case of nonconvulsive status epilepticus as a complication of chemotherapy with the nitrogen mustard derivative ifosfamide. Our patient developed encephalopathy, upper extremity myoclonus, and a periodic, triphasic electroencephalogic pattern that resolved acutely with intravenous diazepam treatment. Since significant morbidity and mortality is associated with unrecognized status epilepticus, electroencephalogic monitoring and a trial of diazepam is indicated in encephalopathic patients with rhythmic electroencephalogic patterns while receiving treatment with ifosfamide. PMID- 8215973 TI - An introduction to the molecular genetics of neurological disease. Recent advances. PMID- 8215975 TI - Molecular genetics of Alzheimer's disease. AB - The part that genetics plays in the origin of Alzheimer's disease (AD) is a complex problem that is only now, in the last few years, beginning to be understood. Progress in the study of the epidemiology of AD, discovery of multiple AD loci, and interpreting how mutations affect and produce the AD phenotype have been the initial keys to unlocking the mysteries of this disease. We now know of the existence of at least three AD loci on chromosomes 14, 19, and 21 and are beginning to understand the role that one of these loci, APP, and its mutations plays in the progression of AD. On future studies using animal modeling and the positional cloning of the other AD loci, a definite model for AD should become evident within the next few years. PMID- 8215974 TI - Molecular genetics of Huntington's disease. AB - Huntington's disease is an inherited disorder in which selective neuronal loss in the brain leads to a characteristic choreic movement disorder. The successful mapping of the Huntington's disease gene to chromosome 4 set off a torrent of similar studies in other inherited disorders as investigators attempted to locate and isolate human disease genes with this new approach. Although it took a decade long quest since the initial mapping of the genetic defect, the gene causing Huntington's disease has recently been isolated. Discovery of the mutational mechanism causing Huntington's disease has explained some of the peculiarities of inheritance of this intriguing disorder and creates hope for a better understanding of the cause of neuronal cell death that could eventually lead to a treatment. PMID- 8215976 TI - The myotonic dystrophy gene. AB - The myotonic dystrophy gene codes for a protein kinase and contains a repeated trinucleotide motif (adenine-guanine-cytosine [AGC]) in its transcribed sequence. The repeat is polymorphic in the general population, varying in size from five to 37 AGC units in normal alleles. Myotonic dystrophy patients show expansions of the repeated sequence from over 50 elements up to several thousand units. There is a positive correlation between repeat size and clinical severity. The direct analysis of the AGC repeat size allows an easy confirmation of the clinical diagnosis of myotonic dystrophy in difficult cases and for prenatal counseling. PMID- 8215977 TI - Charcot-Marie-Tooth syndrome. AB - Charcot-Marie-Tooth syndrome (CMT) is a group of genetically determined symmetric distal polyneuropathies. The CMT loci are known to map to chromosome 1 (CMT1B), chromosome 17 (CMT1A), the X chromosome (CMTX), and two additional unknown autosomes (CMT1C and CMT2). The most prevalent form is CMT1A, an autosomal dominant demyelinative disorder caused either by a tandem duplication in band p11.2-12 of chromosome 17 (17p11.2-12) with trisomic expression of the peripheral myelin protein-22 (PMP-22) gene or, less frequently, by a missense mutation of PMP-22. Missense mutations in PMP-22 are also responsible for two forms of demyelinative polyneuropathy in mice, trembler and trembler. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent focal neuropathy. In all families thus far studied, patients with HNPP have been found to be monosomic for a segment of chromosome 17p11.2-12. The duplication in CMT1A and deletion in HNPP map to the same region in 17p11.2-12 and are both likely to be consequences of unequal crossing over during germ cell meiosis. PMID- 8215978 TI - Neurofibromatosis type 1. Beyond positional cloning. AB - Recent advances in molecular genetics have enabled researchers to more rapidly identify human disease genes. The identification of these genes by positional cloning has opened the door to a better understanding of such diseases through a more complete appreciation of the molecular biologic processes that underlie them. In this review, the approaches taken to dissect the function of the gene for von Recklinghausen neurofibromatosis are presented. These general approaches involve identification of the protein product, determination of its relation to other known proteins, analysis of its distribution in tissues, within cells, and over development, and dissection of its role in producing the disease phenotype. Last, the insights gained from studying the molecular biology of the neurofibromatosis type 1 gene have direct impact on other biologic processes, such as neoplasia, cellular differentiation, and growth factor-mediated signal transduction as well as potential application to improved treatments for neurofibromatosis type 1 and cancer. PMID- 8215979 TI - Mitochondrial encephalomyopathies. AB - Mitochondrial diseases are uniquely interesting from a genetic point of view because mitochondria contain their own DNA (mtDNA) and are capable of synthesizing a small but vital set of proteins, all of which are components of respiratory chain complexes. Numerous mutations in mtDNA have been described in the past 5 years, and, it is, therefore, important for the clinician to keep in mind both some characteristic clinical presentations and, more importantly, some basic principles of "mitochondrial genetics," including heteroplasmy, the threshold effect, mitotic segregation, and maternal inheritance. The vast majority of mitochondrial proteins are encoded by nuclear DNA (nDNA) and have to be imported from the cytoplasm into mitochondria through a complex translocation machinery, which is also under the control of the nuclear genome. In addition, nDNA encodes several factors that control mtDNA replication, transcription, and translocation. Mitochondrial diseases due to mutations in nDNA are transmitted as mendelian traits and fall into three categories: (1) alterations of mitochondrial proteins; (2) alterations of mitochondrial protein importation; and (3) alterations of intergenomic communication. The first group of disorders can be further classified on the basis of the biochemical area affected, including defects of transport, defects of substrate utilization, defects of the Krebs cycle, defects of oxidation/phosphorylation coupling, and defects of the respiratory chain. The second group includes only few well-documented disorders but will certainly expand in the near future. The third group includes two conditions, an autosomal dominant form of progressive external ophthalmoplegia associated with multiple mtDNA deletions, and a quantitative defect of mtDNA (mtDNA depletion) causing severe infantile myopathy or hepatopathy. PMID- 8215980 TI - The role of neurogenetics in Gaucher disease. AB - Gaucher disease is the most prevalent hereditary metabolic storage disorder, and the most common genetic disease in individuals of Ashkenazic Jewish ancestry. Patients with Gaucher disease have been classified into three clinical phenotypes. Patients with type 1 disease exhibit markedly variable hepatosplenomegaly, anemia, thrombocytopenia, skeletal, and, to a lesser extent, pulmonary and kidney involvement. The central nervous system does not appear to be involved. In patients with type 2 Gaucher disease, hepatosplenomegaly and extensive central nervous system damage are apparent in infancy. These patients usually die between 1 and 2 years of age. Patients with type 3 Gaucher disease have been subclassified into types 3a and 3b. Type 3a patients exhibit mild-to moderate hepatosplenomegaly and slowly progressive neurologic deterioration. Recurrent myoclonic seizures are common. Patients with type 3b Gaucher disease exhibit splenomegaly along with extensive hepatomegaly that is frequently accompanied by esophageal varices. Horizontal supranuclear gaze paresis is the major neurologic sign. Excessive quantities of glucocerebroside accumulate in the organs of patients with Gaucher disease because of a deficiency of the enzyme glucocerebrosidase. In the vast majority of patients, the reduction of glucocerebrosidase activity is caused by mutations in the gene that codes for glucocerebrosidase. In a few instances, glucocerebroside accumulates due to a lack of saposin C, a cohydrolase that is required in addition to glucocerebrosidase for the catabolism of glucocerebroside. Mutations in the glucocerebrosidase gene are discussed in the context of the severity of disease and the presence or absence of nervous system involvement. Enzyme replacement therapy is highly beneficial for patients with type 1 Gaucher disease. Enzyme replacement is also being investigated for patients with type 3b Gaucher disease. Novel procedures must be developed to deliver glucocerebrosidase to the nervous system so that patients with type 2 and type 3a Gaucher disease can be helped. Exploration of gene therapy for Gaucher disease is under way. PMID- 8215981 TI - Duchenne-Becker muscular dystrophy and the nondystrophic myotonias. Paradigms for loss of function and change of function of gene products. AB - Recessively inherited disorders can most often be considered loss of function: the patient has only defective copies of the defective gene (homozygous or hemizygous), with little or no functional protein products produced. Dominantly inherited disorders can most often be considered change of function: the patient has both mutant and normal copies of the gene (heterozygous); however, the mutant gene produces an abnormal protein product that causes dysfunction of the cell. Categorization of inherited disorders simply by their inheritance pattern thus affords some predictions concerning the underlying biochemical defect. To illustrate these generalizations, the molecular data on two important human inherited neurologic disorders will be described. X-linked recessive Duchenne/Becker muscular dystrophy has been shown to caused by loss of function of the dystrophin product. Dominantly inherited hyperkalemic periodic paralysis and paramyotonia congenita have been shown to be the result of single amino acid changes of the skeletal muscle voltage-sensitive sodium channel that alter the channel's function in response to environmental or physiologic stimuli (change of function). PMID- 8215982 TI - Genotype-phenotype correlations in human skeletal muscle sodium channel diseases. AB - BACKGROUND: Over the past 3 years, the genetics of the myotonic diseases have been substantially elaborated. Three genetically different groups of myotonic disease can be discerned: (1) the chloride channel myotonias, (2) the adynamia paramyotonia complex, and (3) myotonic dystrophy. METHODS AND RESULTS: Electrophysiology has suggested and molecular biology has proven that the diseases belonging to the adynamia-paramyotonia complex, ie, paramyotonia congenita, hyperkalemic and normokalemic periodic paralysis, and some rare forms of myotonic disease, are caused by point mutations in the gene encoding the alpha subunit of the sodium channel in adult human skeletal muscle, located on chromosome 17q23. Thirteen different mutations have been described by various groups in the United States and Germany. The various mutations causing a particular form of the complex are not located in the gene in a predictable or easily understandable regular manner. CONCLUSIONS: Further study of the genotype phenotype correlations should not only increase our understanding of the variability of signs in this group of diseases, it could also provide us with a deeper insight in the function of the various regions of the sodium channel protein. PMID- 8215983 TI - Gene therapy for neurologic disease. AB - Gene therapy is a potentially potent new method of treating a number of neurologic disorders previously considered refractory to current conventional therapeutic treatments. Numerous advances have been made in the construction of expression vectors, cellular and viral transgene carriers, and the characterization of target cells for neuronal gene therapy. Two primary approaches to nervous system gene transfer have emerged as a result of these advances. The in vivo approach concentrates on direct transfer of genetic material to cells in vivo using viral and chemical agents. The ex vivo approach relies on genetic transfer to cultured cells that are subsequently implanted into a host organism. Both of these methods have been used in preliminary experiments designed to test the efficacy of gene transfer strategies in the amelioration of nervous system dysfunction. PMID- 8215984 TI - A neurological gene map. PMID- 8215985 TI - The influence of age on collagen and non-collagen protein production by human gingival epithelial cells. AB - The effects of donor age on the proliferation and secretory phenotype of cultured human gingival epithelial cells were investigated. Pure cultures of epithelial cells were isolated from human gingiva of old (61-75 yr) and young (18-30 yr) adults and serially cultivated in a serum-free medium at 37 degrees C in humidified air containing 5% CO2. For each experiment, cells were seeded at 150/mm2 and the medium changed every other day. Cell number, collagen and non collagen protein production and relative collagen synthesis (percentage collagen synthesized) were determined at days 2, 4, 6 and 8. Epithelial strains from old and young adults became confluent by day 8 and there were no differences in their rates of proliferation. Likewise there was no difference in collagen production between the two groups; however, cells from elderly individuals produced significantly less non-collagen protein. Over time the decrease in non-collagen protein production ranged from 56% below the non-collagen protein levels of epithelium from young adults at day 2 to 24% below at day 8. The reduction of non collagen protein coupled with the unchanged secretion of collagen resulted in a statistically significant increase in relative collagen synthesis by epithelial cells from elderly individuals. These differences in non-collagen protein production and relative collagen synthesis by cultured gingival epithelium of old adults suggest a selective conversion in protein secretion. PMID- 8215986 TI - The importance of the culture medium on human dental pulp cell attachment. AB - Radiochromium-labelled pulpal cells were cultured with nine commercially available media and conditioned minimal essential (MEM) medium. Radiochromium release from the 10 cell cultures was recorded after 4 h of incubation. Cells cultured with MEM and conditioned MEM were examined by scanning electron microscopy (SEM) after 2, 4, 8 and 24 h of incubation to study possible differences in attachment. Radiochromium release from cells cultured with most of the media was very high, indicating damage to the external cell membrane. When cells were cultured with conditioned medium, the radiochromium release was within acceptable limits. SEM showed faster attachment when cells were cultured with conditioned MEM. The data indicate that pulpal cells should be cultured with conditioned medium for better results in short-term cytotoxicity experiments with the radiochromium release method. PMID- 8215987 TI - Basic and lectin histochemistry for studying glycoconjugates in the lingual salivary glands of the Japanese quail (Coturnix coturnix japonica). AB - Traditional non-lectin staining methods and lectin histochemistry combined with specific exoglycosidase digestion were used to investigate the histological structure of these glands and to visualize the occurrence and composition of salivary glycoconjugates. The quail lingual glands comprise the anterior lingual gland, with rostral and caudal portions that differ in morphology and histochemical staining, and the posterior lingual gland devoid of regional differences. Carbohydrate histochemistry further differentiated the secretory structures by revealing a heterogeneous cell population of tubules within the rostral and caudal portions of the anterior gland, and a rather homogeneous staining of the tubuloalveolar elements in the rostral portion of the anterior lingual gland and in the posterior gland. Tubuloalveolar secretory cells mainly produced sulphate-containing molecules. In addition, sialoglycoconjugates were present in both anterior and posterior lingual glands, whereas fucoglycoconjugates were visualized only in the anterior gland. PMID- 8215988 TI - Cultural and morphological characteristics of human periodontal ligament cells in vitro. AB - Primary cell lines from explants of human periodontal ligament were established in vitro to assess their suitability as test cells in a biocompatibility assay. They were maintained over nine passages. The constituent fibroblast-like cells (F cells) were monitored throughout by light and electron microscopy. Although F cells from several different donors displayed stable and consistent growth characteristics, after the ninth subculture changes in the fine structure suggested that some cells were undergoing differentiation or senescence. It is therefore recommended that cells from earlier passages be used in in vitro biocompatibility assays. PMID- 8215989 TI - Characteristics of periodontal mechanoreceptors supplying cat canine teeth which have sustained orthodontic forces. AB - The characteristics of these mechanoreceptors were investigated after orthodontic forces had been applied for either 3 days or 12 weeks, and also 8 weeks after the tooth had been moved into a new position and the tissues allowed to recover. Electrophysiological recordings were made from single mechanosensitive units dissected from the inferior alveolar nerve and each was characterized by applying forces to the tooth crown. The characteristics were compared with those of receptors innervating normal teeth. Three days after the onset of tooth movement, the periodontal mechanoreceptors had higher thresholds to forces applied at slow rates and lower discharge frequencies. Twelve weeks after the onset of tooth movement, the mechanoreceptors again had higher force thresholds and lower discharge frequencies but also responded to applied forces over a narrower range of directions and adapted more rapidly than the controls. After the tooth had been moved into a new position and the tissues allowed to recover, the mechanoreceptor characteristics were nearer to normal but they still had raised thresholds to forces applied at slow rates, lower discharge frequencies, and responded to applied forces over a narrower range of directions. It seems likely that the altered receptor characteristics would have resulted from a combination of disorganization of the collagen matrix and direct injury to the nerve terminals. PMID- 8215990 TI - Expression, localization and developmental regulation of insulin-like growth factor I mRNA in rat submandibular gland. AB - The mRNA for insulin-like growth factor I (IGF-I) in the submandibular gland of mature and developing rats was examined by Northern blotting and in situ hybridization with an oligonucleotide probe. In the mature adult rat, IGF-I mRNA was expressed at a higher level in the submandibular gland than in the liver, and was localized primarily in the granular convoluted tubule (GCT) cells. A 4.7-kb mRNA on Northern blots, which was expressed only slightly in the liver, proved to be the predominant size species of IGF-I transcripts in the GCT cells, and its level increased progressively with the postnatal development of GCTs in the gland. In addition, a 1.8-kb mRNA for IGF-I was also expressed at a much lower level throughout the acinar and duct systems, irrespective of age. These results have shed a light on the status of IGF-I as one of the many biologically active polypeptides that are produced in the rodent submandibular gland. PMID- 8215991 TI - The practicability of finite-element analysis for assessing changes in human craniofacial morphology from cephalographs. AB - The usefulness of a finite-element analytical (FEA) method for studying changes in facial form was investigated. The material was lateral cephalographs of 19 patients who had undergone surgical correction of the chin. FEA was used to assess changes in bony form brought about by surgery. Replicate digitization of cephalographic landmarks was used to minimize measurement error. Random and systematic errors were examined and their influence on the finite-element method was assessed. However, the sensitivity of FEA is such that the level of residual measurement error affects the reliability of the method and makes the technique unsuitable for individual cases. However, for pooled data from a group of cases the effect of measurement error is reduced and the reliability of the analysis is satisfactory for intergroup comparison. PMID- 8215992 TI - Fibre type distribution in the muscle spindles of cat jaw-elevator muscles. AB - Small samples of the masseter and temporalis muscles of six adult male cats were dissected free, snap-frozen and cryosectioned. Serial sections from areas with muscle spindles were histochemically stained for myofibrillar ATPase after incubation in acid and alkali buffer, and for reactivity to two different myosin isoform-specific antibodies. Differential reactivity to these four stains identified bag1, bag2 and chain intrafusal fibre types. The most typical distribution of fibres within the spindle was 1 bag1, 1 bag2 and 3-4 chains. Although a few spindles were found in the anterior area of the temporalis that attaches to the coronoid process of the mandible and in the anterior area of the superficial masseter, the vast majority were found in the deepest portion of the masseter. Here spindles were characteristically with a number of simple spindles fused together into complex units. PMID- 8215993 TI - Bilateral asymmetries in the jaw-jerk reflex activity in man. AB - In order to investigate whether there are bilateral differences in the sensitivity of the mandibular stretch (jaw-jerk) reflex between patients with a myogenous craniomandibular dysfunction (CMD) and healthy controls free from signs and symptoms of CMD, jaw-jerk reflexes were elicited under standardized conditions in two groups of 10 gender- and age-matched subjects. The reflexes were recorded bilaterally from the masseter and the anterior temporal muscles by means of bipolar surface electromyogram (EMG). Reflex amplitudes at a mandibular displacement of exactly 80 microns and at a background muscle activity of exactly 12% maximum voluntary contraction were determined from relations between reflex amplitude and jaw displacement. These were obtained at a visually controlled, constant clenching level. For both groups, comparisons were made between reflex amplitudes from the right- and the left-hand side. In CMD patients with predominantly unilateral jaw muscle pain, comparisons were also made between the pain and non-pain sides. Although significant side asymmetries were found in many individuals, no significant differences were found among bilateral asymmetries in reflex sensitivity between patients and controls. No influence of pain side on the asymmetries was found. It was concluded that neuromuscular factors do not cause significant bilateral differences in the sensitivity of the jaw-jerk reflex between patients with myogenous CMD and controls. In a control experiment, in which eight healthy control subjects participated, the influence of a possible asymmetry in jaw displacement on the reflex sensitivity was evaluated. To achieve this, reflexes were elicited not only by means of a bilaterally imposed mandibular load, but also by means of loading via a unilateral bite-fork, so that an equal, constant jaw displacement could be imposed successively on both sides of the mandible. As no significant differences were found in bilateral asymmetries in reflex sensitivity between unilateral and bilateral mandibular loading, the influence of a possible asymmetrical jaw displacement on side asymmetries in the jaw-jerk reflex sensitivity is negligible in our experimental model. PMID- 8215994 TI - The effect of the consistency of the diet on eruption rates and lengths of incisor teeth in rats. AB - It is uncertain whether the consistency of the diet affects the eruption of rodent incisors. One study reported that harder diets made incisors shorter and erupt faster, and suggested that the faster eruption was due to the decreased length. Two other studies found no effect on eruption rates. In the present study the impeded and unimpeded eruption rates of these lower incisors were measured, using ether anaesthesia for all procedures. There were two groups of rats fed in alternate periods on standard laboratory pellets and in the intervening periods on the same material ground to a powder. In each period, one group was fed on pellets and the other on powder. The impeded eruption rate was less when the rats were fed on powder than on pellets and the rate declined with time. The unimpeded incisors were not affected by the diet, so the effects on the impeded incisor were direct effects on the tooth and not systemically mediated. The impeded incisors lengthened during the experiment and the lengthening was greater on powder than on pellets. The ratio of the change in impeded eruption rates to the increase in tooth length on changing from pellets to powder was different from the ratio for going from powder to pellets, so the effect of the diet on the impeded eruption rate was not due to the change in length of the teeth. There was a negative correlation between the decline in impeded eruption rates and the lengthening of the incisor with time, suggesting that tooth length can influence eruption rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8215995 TI - Developmental pattern and subcellular localization of parvalbumin in the rat tooth germ. AB - The EF-hand calcium-binding protein parvalbumin has been extensively studied in nerve and muscle cells. Its possible role in biomineralization during tooth development was here investigated by determining its subcellular localization by immunogold cytochemistry. The developmental sequences of amelogenesis and dentinogenesis were studied in rat molars, and in continuously growing rat incisors. The findings confirm that parvalbumin is a nuclear and a cytosolic protein, not associated with any particular intracellular organelle. Epithelial and mesenchymal undifferentiated cells contained no specific parvalbumin immunolabelling. In differentiated ameloblasts, secretory-pole (Tomes' process) formation was associated with a proximal-distal gradient of parvalbumin labelling. But after the Tomes' process had formed, parvalbumin was evenly distributed throughout the cell. The parvalbumin contents of ruffle-ended and smooth-ended ameloblasts appeared to be very different. Differentiated odontoblasts were less heavily labelled than ameloblasts, and the label was restricted to the cell body during the whole of dentinogenesis. These data suggest that parvalbumin could contribute to membrane plasticity during differentiation, as shown during dendritic growth in the nervous cells. Moreover, as may occur in excitable cells, parvalbumin could buffer calcium specifically in the cells producing mineralized enamel and dentine during the later stages of tooth development. PMID- 8215996 TI - The protein of pigmented Polynesian dental enamel. AB - This enamel contained 1.4-3.7% protein, calculated from amino acid residues, in which glutamic acid and leucine were the most generally abundant and lysine was the most abundant basic amino acid. The amino acid profiles of both French Polynesian and Maori pigmented enamel protein were similar and closely resembled that of tuft protein and certain non-amelogenins. Sodium dodecyl sulphate polyacrylamide gel electrophoresis of extracts of pigmented enamel showed an absence of amelogenin protein and the presence of two principal proteins at M(r) 55,000-66,000, indicating that the protein of pigmented Polynesian enamel was non amelogenin. This contrasts with hypomaturation amelogenesis imperfecta in which the protein has the amino acid profile of amelogenin. PMID- 8215997 TI - Appearance of neuropeptide Y-like immunoreactive cells in the rat trigeminal ganglion following dental injuries. AB - The effects of these injuries on the presence and distribution of neuropeptide Y (NPY)-immunoreactive (-IR) neurones were examined immunohistochemically. In the normal trigeminal ganglion: some perivascular nerves displayed NPY-IR but there were no NPY-IR ganglionic cells. Fourteen days after extraction or pulp exposure of the upper first molar, NPY-IR cells appeared in the maxillary region of the trigeminal ganglion. About 90% of the injury-evoked NPY-IR cells had medium to large diameters (more than 300 microns2 in cross-sectional area). Shallow cavity preparation, however, did not induce the appearance of NPY-IR cells in the trigeminal ganglion. These results indicate the dental injuries alter the primary sensory neurones in the trigeminal ganglion. PMID- 8215998 TI - Alcohol and cataract. PMID- 8215999 TI - Factors influencing response to strabismus surgery. PMID- 8216000 TI - Timolol-pilocarpine fixed-ratio combinations in the treatment of chronic open angle glaucoma. PMID- 8216001 TI - A new guideline for cataract. PMID- 8216002 TI - Visual fields in optic neuritis. PMID- 8216003 TI - Retinal detachment caused by air bag injury. PMID- 8216004 TI - Air bag-associated ocular injury. PMID- 8216005 TI - Air bag injury producing retinal dialysis and detachment. PMID- 8216006 TI - Corneal edema, hyphema, and angle recession after air bag inflation. PMID- 8216007 TI - Orbital cellulitis after retrobulbar injection of chlorpromazine. PMID- 8216008 TI - Stromal keratitis associated with Epstein-Barr virus infection in a young child. PMID- 8216009 TI - Scleritis in association with poststreptococcal vasculitis. PMID- 8216010 TI - Ocular fluconazole treatment of Candida parapsilosis endophthalmitis after failed intravitreal amphotericin B. PMID- 8216011 TI - Who does cataract surgery in the United States? PMID- 8216012 TI - Air bag: friend or foe? PMID- 8216013 TI - Magnification and visual acuity in refractive surgery. AB - In comparisons of retinal image size within the same eye before and after refractive surgery, a change in the plane of correction from the spectacle to the cornea induces a change in retinal magnification. Comparing retinal image size between eyes of different individuals, a change in the plane of correction as well as the type of ametropia (axial or refractive) interacts to change the retinal magnification. Consequently, comparing acuity before and after refractive surgery without considering the effects of retinal magnification can be misleading. Magnification effects can be large, accounting for a visual acuity increase of 1 line or more. Here we model the magnification induced by refractive surgery in various reference eyes and discuss implications in the context of current clinical trials. PMID- 8216014 TI - Four-week safety and efficacy study of dorzolamide, a novel, active topical carbonic anhydrase inhibitor. AB - OBJECTIVE: To investigate the activity and local and systemic safety of the topical carbonic anhydrase inhibitor, dorzolamide hydrochloride. DESIGN: Four week, double-masked, randomized, placebo-controlled, parallel, three-center study. SETTING: Referral centers. PATIENTS: Forty-eight patients with bilateral open angle glaucoma or ocular hypertension and intraocular pressure (IOP) greater than 22 mm Hg entered the study. Two of 28 patients receiving dorzolamide and two of 20 patients receiving placebo were withdrawn due to adverse experiences. INTERVENTION: Dorzolamide (2%) or placebo to each eye three times daily for 4 weeks. MAIN OUTCOME MEASURES: Diurnal IOP curves; ophthalmologic evaluations including corneal ultrasound pachymetry and endothelial cell count; and systemic evaluations including vital signs, blood chemistries, complete blood cell counts, urinalysis, electrocardiogram, and drug and carbonic anhydrase activity levels in red blood cells. RESULTS: Mean IOP at morning trough (8 AM) decreased from 27.1 mm Hg at baseline to 23.5 mm Hg on day 29 with dorzolamide (-13.3%) compared with a decrease from 27.1 mm Hg to 26.4 mm Hg with placebo (-2.3%). Peak activity occurred 2 hours after administration, with IOP decreasing from 26.8 mm Hg at baseline to 21.8 mm Hg on day 29 with dorzolamide (-18.4%) vs 26.1 mm Hg to 25.5 (-2.4%) with placebo. Mean corneal thickness was slightly increased for the dorzolamide-treated group compared with the placebo-treated group (0.009 mm vs 0.001 mm, respectively, P < .05) and changes in endothelial cell counts were similar (-24 cells/mm2 vs -27 cells/mm2, respectively, P > .25). Mean carbonic anhydrase isoenzyme II activity in red blood cells decreased to 21% of baseline in dorzolamide-treated patients. There were no clinically significant differences in ocular or laboratory parameters between the dorzolamide and placebo groups. CONCLUSIONS: Dorzolamide demonstrated significant IOP lowering activity over 4 weeks. It was well tolerated and there were no clinically significant changes in ocular or systemic safety parameters. PMID- 8216015 TI - The effects on aqueous dynamics of PhXA41, a new prostaglandin F2 alpha analogue, after topical application in normal and ocular hypertensive human eyes. AB - OBJECTIVE: To study the effects of a topically applied prostaglandin F2 alpha analogue, PhXA41 (Latanoprost; 13,14-dihydro-17-phenyl-18,19,20-trinor prostaglandin F2 alpha-isopropyl ester), on aqueous dynamics in the human eye. DESIGN: A randomized, double-masked study was carried out on 20 normal and 20 ocular hypertensive humans. One eye of each subject was treated with 0.006% PhXA41, while the contralateral eye received placebo twice daily for 5 days. MAIN OUTCOME: Compared with placebo, PhXA41 reduced intraocular pressure in both groups by approximately 20%. RESULTS: Tonographic facility of outflow was increased 24% in the normal group and 30% in the ocular hypertensive group; no changes were observed in the rates of aqueous humor flow in either group. The changes in tonographic facility were insufficient to fully explain the ocular hypotensive effect of the drug, suggesting that PhXA41 enhances outflow via the uveoscleral pathway. The suitability of fluorophotometry as a measure of flow was confirmed by three methods of comparing blood-aqueous barrier permeability: polarization of cameral fluorescence, intensity of backscattered light from the anterior chamber (flare), and cameral fluorescence after oral administration of fluorescein sodium. All of these measured parameters were normal, suggesting that this compound has no clinically significant effects on the blood-aqueous barrier or on the accuracy of fluorophotometry. PhXA41 was well tolerated in both groups. Only four of 40 subjects reported a transient foreign-body sensation, and only one of 40 subjects was observed to have greater than moderate conjunctival hyperemia. Most subjects had no symptoms and no measurable hyperemia. CONCLUSIONS: These results suggest that PhXA41 is a potentially useful ocular hypotensive agent that enhances the egress of aqueous humor via both major outflow pathways. The relative lack of ocular side effects in this study further suggests that this agent has promise for the treatment of chronic glaucoma. PMID- 8216016 TI - Combination ganciclovir and foscarnet in the treatment of clinically resistant cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. AB - OBJECTIVE: To assess the clinical response and patient tolerance to daily infusions of both ganciclovir sodium and foscarnet sodium for the treatment of clinically resistant cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. DESIGN AND PATIENTS: Nine patients with clinically resistant cytomegalovirus retinitis who had shown progression of retinitis despite extended intravenous induction single-drug therapy or alternating therapy with induction doses of ganciclovir or foscarnet at 6 weeks were subsequently treated with a combination of ganciclovir and foscarnet. The dosing regimen for induction combination therapy was ganciclovir at 5 mg/kg every 12 hours and foscarnet at 60 mg/kg every 8 hours. Maintenance combination therapy was ganciclovir at 5 mg/kg every 12 to 24 hours and foscarnet at 90 to 120 mg/kg every day. Patients were observed closely for signs of a toxic effect or intolerance to the drug regimen. RESULTS: All patients exhibited a favorable response to combination therapy, with complete healing of retinitis in 12 of 14 eyes and partial healing of retinitis with decreased border activity and a cessation of border advancement in two of 14 eyes. Two of the nine patients stopped receiving combination therapy before completion of the study owing to their dissatisfaction with the time commitment. The regimen was otherwise well tolerated, with no significant medical toxic effects attributable to the drugs requiring cessation of therapy. CONCLUSIONS: Combination anticytomegalovirus therapy should be considered in those patients who have shown a poor clinical response to sustained single-drug induction therapy and alternating drug therapy. As survival time for patients with cytomegalovirus retinitis continues to improve, clinical resistance may become more common. Further work to delineate the optimal dosing and indications for combination therapy will be important. PMID- 8216017 TI - Bone marrow transplantation and cataract development. AB - OBJECTIVES: To evaluate risk factors for the development of posterior subcapsular cataract following bone marrow transplantation (BMT) and the results of patients undergoing cataract extraction. DESIGN: Retrospective case-control study. SETTING: Tertiary referral center. PATIENTS: Three hundred sixty-six patients (59% male, 41% female) undergoing BMT at one institution who survived for at least 1 month and underwent full ophthalmologic examination. Risk factors were then compared between patients who developed posterior subcapsular cataract and those who did not. INTERVENTION: Cataract surgery in six eyes of four patients. MAIN OUTCOME MEASURE: Formation of posterior subcapsular cataract. Data were obtained on all patients for type of BMT, pretransplantation regimen, underlying malignancy, demographic background, complications of BMT, and medications. RESULTS: Forty (10.9%) of 366 patients developed posterior subcapsular cataract. By univariate analysis, cataract formation was associated with total body irradiation, chronic graft-vs-host disease, the use of allogeneic bone marrow, and the total dose and duration of corticosteroid therapy. Multivariate analysis revealed that the total dose and duration of corticosteroid therapy were the most important risk factors, while total body irradiation was not a statistically significant risk factor. Cataract surgery was performed in six eyes of four patients, all of whom developed visual acuities of 20/40 or better. CONCLUSION: Posterior subcapsular cataract following BMT is uncommon and rarely requires surgery. Total dose and duration of corticosteroid therapy are the most important risk factors for development of cataract, but total body irradiation is not a statistically significant risk factor. PMID- 8216018 TI - Corneal thickness changes after high-risk penetrating keratoplasty. Collaborative Corneal Transplantation Study Group. AB - OBJECTIVE: To determine whether ultrasonic measurements of corneal thickness are of prognostic value after high-risk penetrating keratoplasty. DESIGN: A prospective, multicenter, randomized trial. PATIENTS: Four hundred fifty patients at high risk for graft failure because of previous immunologic graft failure or because of two or more quadrants of stromal vascularization. Patients underwent surgery and were treated according to a specific protocol and observed at frequent intervals. INTERVENTION: At each postoperative visit, ultrasonic measurement of central corneal thickness was performed and the corneal status was determined by biomicroscopic examination. MAIN OUTCOME MEASURE: Graft failure owing to immunologic or nonimmunologic causes. RESULTS: Corneal thickness stabilized by 3 months at a median thickness of 0.54 mm. The range of corneal thicknesses in patients with corneal grafts judged to be clear was large. In 49% of eyes, development of an allograft reaction episode was accompanied by an increase in corneal thickness of at least 10%; the greater the increase in thickness, the more likely the graft would fail. Clear grafts with central thicknesses of 0.59 mm or greater at 1, 3, or 6 months had a much greater risk of failure than those with thicknesses of less than 0.59 mm. CONCLUSION: Corneal thickness measurements after high-risk penetrating keratoplasty are of prognostic value. PMID- 8216019 TI - Impact of delayed treatment in growing posterior uveal melanomas. AB - OBJECTIVE: To investigate the impact of pretreatment tumor growth on survival in patients with primary posterior uveal melanoma. DESIGN: Retrospective case-by case matched comparative survival study. PATIENTS: Thirty patients with documented tumor growth of at least 3 mm in basal diameter, 1.5 mm in thickness, or both during a pretreatment interval of 6 months or more and a matched control group of 30 promptly treated patients. Matching criteria included patient age (+/ 10 years), largest basal tumor diameter (+/- 2 mm), tumor thickness (+/- 1.5 mm), location of anterior tumor margin (same defined zone), and visual symptoms (present or absent). SETTING: The Oncology Unit of the Retina Service at Wills Eye Hospital, Philadelphia, Pa. INTERVENTIONS: All patients were treated in a nonrandomized fashion by conventional therapeutic methods appropriate to the tumor's size, location, and other factors. MAIN OUTCOME MEASURES: Actuarial melanoma-specific mortality and all-cause mortality. RESULTS: The mean +/- SE cumulative 5-year probability of melanoma-specific mortality relative to the date of initial examination was 17.1% +/- 7% in the delayed treatment group and 18.4% +/- 8% in the prompt treatment group. This difference is not statistically significant (P > .5, log rank test). CONCLUSIONS: These results lend support to the belief that delayed treatment of selected small and dormant-appearing choroidal and ciliary body melanomas does not substantially increase the probability of melanoma-specific mortality; however, they do not prove that observation is the correct management option for all patients with a posterior uveal melanoma. PMID- 8216020 TI - Remitting sixth nerve palsy in skull base tumors. AB - OBJECTIVE: Spontaneous recovery of a sixth nerve palsy is thought to rule out a neoplastic origin. We reviewed cases of sixth nerve palsy that improved without treatment but that ultimately proved to be caused by a tumor at the base of the skull. DESIGN: Case series. SETTING: Hospital-based, neuro-ophthalmology referral practice. PATIENTS: Seven patients with an age range from 7 to 61 years had sixth nerve palsy secondary to a slow-growing neoplasm at the skull base. MAIN OUTCOME MEASURES: Return of lateral rectus function and resolution of diplopia without intervention. RESULTS: Seven patients with sixth nerve palsy caused by skull base tumors experienced spontaneous improvement of their deficit. Recovery time ranged from 1 week to 18 months. No patient was diabetic or had evidence of vascular disease. In one patient, the palsy improved once prior to becoming a fixed deficit, and spontaneous improvement occurred on two to five occasions in the other patients. CONCLUSION: Spontaneous recovery of a sixth nerve palsy can occur in the presence of an extramedullary compression by a tumor at the base of the brain. Possible mechanisms for recovery include remyelination, axonal regeneration, relief of transient compression (eg, resorption of hemorrhage), restoration of impaired blood flow, slippage of a nerve previously stretched over the tumor, or immune responses to the tumor. PMID- 8216021 TI - Intraocular cilia. Report of six cases of 6 weeks' to 32 years' duration. AB - In this study, we describe the clinicopathologic features seen in six cases of intraocular cilia and review the features of previously reported cases. Ultrastructural studies of the cilia showed partial loss of the cuticle layer, diffuse accumulation of small electron-dense granules in cuticle and cortical cells, and loss of continuous cell membranes of the cortex. The cilia were almost completely intact in most of our cases. Intraocular cilia can be tolerated for long periods. PMID- 8216022 TI - Polyphenotypic small-cell orbitocranial tumor. AB - A male infant was born with a massive orbitocranial tumor without evidence of metastasis. On light microscopy, the histologic pattern of the tumor was that of a largely necrotic and highly undifferentiated small round cell neoplasm of uncertain origin. Ultrastructural features of the primitive cells included a rare tight junction and myofibril. Immunohistochemical studies showed positive staining for cytokeratin, vimentin, muscle-specific actin, neuron-specific enolase, and S100 protein and negativity for desmin and leukocyte common antigen. We believe this case represents an example of a polyphenotypic small-cell tumor of childhood with epithelial, rhabdomyoblastic, and neuroectodermal differentiation. PMID- 8216023 TI - Examination methods for glaucoma prevalence surveys. AB - OBJECTIVE: To perform a pilot evaluation of new examination methods for the detection of glaucoma and other causes of visual impairment in rural East Africa. DESIGN: Testing was performed by local eye nurses after a brief training course. Two novel tests of visual function were used, a scotopic sensitivity test and a visual field test performed on a laptop computer. The optic disc was examined with direct ophthalmoscopy after pupillary dilation and compared with standard photographs on a laminated card. Intraocular pressure was measured with a hand held, electronic tonometer. SETTING: Rural Tanzania. PARTICIPANTS: One hundred twenty adult villagers. RESULTS: The visual function tests could be performed on more than 90% of subjects, and the results were correlated with the size of the optic disc cup, an objective measure of glaucoma injury. CONCLUSIONS: This survey shows the practicality of instrument-based testing of visual function under field conditions. PMID- 8216024 TI - Xanthoma disseminatum. PMID- 8216025 TI - Patch grafts of dehydrated cadaveric dura mater for tube-shunt glaucoma surgery. AB - Human donor sclera is commonly used in glaucoma surgery with a tube-shunt (eg, Molteno, Baerveldt, Shocket, Krupin-Denver) to cover the external portion of the silicone tube and prevent its erosion through the overlying conjunctiva. Common problems with this technique include immune-mediated melting of the graft and the potential for infectious disease transmission by the grafted material. A case is presented of a patient in whom a low-grade iridocyclitis was associated with the gradual melting of a scleral patch graft; the scleral patch was then replaced with commercially available, dehydrated human dura mater. The practical and theoretical advantages of cadaveric human dura mater in tube-shunt glaucoma surgery are discussed. PMID- 8216026 TI - Repeatability of distortion product otoacoustic emissions in normally hearing humans. AB - Distortion product otoacoustic emissions (DPOAEs) at the frequency of 2f1-f2 were measured in one or both ears of 12 young adults during 4 test sessions over a 6 week period. The purpose was to determine the variability in DPOAE amplitudes and 'detection thresholds' over repeated measurements using a computer-based time averaging system. DPOAEs were generated with f1 and f2 relative to (f1f2)1/2 in two basic paradigms: (a) fixed levels of L1 = L2 of 70 and 55 dB SPL over a stimulus range from 0.8 to 8 kHz in 0.2-octave intervals; (b) input-output functions in stimulus regions of 0.8, 1, 1.5, 2, 3, 4 and 6 kHz, L1 from 35 to 70 dB SPL changing in 5-dB steps and L2 at 6 dB below the amplitude of L1. The mean variability of DPOAE amplitudes with equilevel stimuli was 1.8 dB (SD = 1.8) for L1 = 70 dB SPL and 2.9 dB (SD = 2.7) for L1 = 55 dB SPL. It was 1.7 dB (SD = 1.7) and 2.4 dB (SD = 2.0) for comparable levels of L1 with L2 at 6 dB below L1. Variability in amplitude of the DPOAEs for the fixed-level condition was greatest overall above 6 kHz and below 1 kHz and in the 2-kHz region for one third of the subjects. Neither individual differences in emission amplitudes nor the presence of spontaneous otoacoustic emissions had a significant influence on the amount of amplitude variability within ears. Variability was not influenced by the length of time between measurements from 1 to 6 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216027 TI - Relationship between evoked otoacoustic emissions and middle-ear dynamic characteristics. AB - Evoked otoacoustic emissions (EOAEs) are considered to originate from outer hair cell movement and to be transmitted to the external auditory meatus through the ossicular chain and eardrum in a retrograde fashion. Therefore, the effect of the middle ear on EOAEs seems to be large. A sweep frequency middle-ear analyzer (MEA) has been developed that gives much more information on middle-ear dynamic characteristics than a conventional impedance meter. In this paper, applying our own EOAE measuring system and the MEA, EOAEs and middle-ear dynamic characteristics of normal subjects were measured, and an attempt was made to clarify the relationship between EOAEs and middle-ear dynamic characteristics. It is concluded that EOAEs are detected most distinctly at the middle-ear resonance frequency and that EOAEs are most detectable in normal subjects whose middle-ear mobility is moderate. PMID- 8216028 TI - Frequency specificity of amplitude-modulation-following response detected by phase spectral analysis. AB - To investigate the frequency specificity of steady-state responses elicited with a sinusoidally amplitude-modulated tone (amplitude-modulation-following response, AMFR), AMFR at different carrier frequencies were examined in 15 subjects with normal hearing, 12 patients with abrupt high-frequency hearing loss, 5 patients with low-frequency hearing loss and 1 patient with mid-frequency hearing loss. The stimulus was a sinusoidally amplitude-modulated tone with a modulation frequency of 40 Hz and modulation depth of 95%. Carrier frequencies were from 250 to 4000 Hz in normal subjects and from 250 to 8,000 Hz in hearing-impaired subjects. Fridman's phase spectral analysis was conducted for automatic detection of response. The thresholds of AMFR were distributed within 30 dB nHL at all carrier frequencies in normal subjects. In the hearing-impaired subjects, AMFR thresholds were between 0 and 25 dB above the behavioral threshold at all carrier frequencies. The threshold patterns of AMFR detected by phase spectral analysis very closely resembled the corresponding audiogram patterns in all types of hearing impairment. AMFR is thus shown to have a very good frequency specificity. PMID- 8216029 TI - Middle-latency responses of awake and anesthetized Japanese macaques. AB - The middle-latency response (MLR) of two Japanese macaques were investigated. In the awake state, the configuration of the MLR components showed two positive peaks: Pa and Pb. The latency and the configuration of Pa were very similar to those of humans. In the topographic recordings, the largest Pa amplitude was found from the vertex, or R1, which is 1 cm lateral to the vertex. In the anesthetic state, Pa and Pb gradually disappeared. This study shows that the MLR in awake Japanese macaques is similar to that in humans, and differs from that in cats. Therefore these awake monkeys are suitable as animal models of human MLR. PMID- 8216030 TI - The perception of complex harmonic patterns by profoundly hearing-impaired listeners. AB - In providing profoundly hearing-impaired persons with processed speech through a signal-processing hearing aid, it is important that the new speech code matches their auditory capacities. This processing capacity for auditory information was investigated in this study. In part 1, the subjects' ability to judge similarities among 8 different but related harmonic complexes was studied. The patterns contained different numbers of harmonics to a 125-Hz fundamental frequency; the harmonics had been spread over the spectrum in various ways. The perceptual judgments appeared to be based on a temporal cue, beat strength, and a spectral cue, related to the balance of high and low frequency components. In part 2, three sets of synthetic vowels were presented to the subjects. Each vowel was realized by summing harmonically related in-phase sinusoids at two formant frequencies. The sets differed in the number of sinusoids per formant: 1, 2 or 3. It was found that the subjects used spectral cues and vowel length for differentiating among the vowels. The overall results show the limited but perhaps usable ability of the profoundly impaired ear to handle spectral information. Implications of these results for the development of signal processing hearing aids for the profoundly hearing impaired are discussed. PMID- 8216031 TI - Hallowell Davis (1896-1992). PMID- 8216032 TI - Diflunisal--a long-acting non-steroidal anti-inflammatory drug. A review of its pharmacology and effectiveness in management of postoperative dental pain. AB - Diflunisal is frequently used for management of postoperative dental pain as it has some advantages over other commonly used non-steroidal anti-inflammatory drugs including improved analgesia, a prolonged duration of action lasting up to 12 hours, and a low incidence of side effects. The aim of this paper is to review the relevant pharmacologic actions of the drug including its mechanism of action in suppressing the inflammatory response, and indications for its use in dentistry. Diflunisal can be safely recommended for the dental patient following oral surgery and exodontia, periodontal surgery and endodontic surgery. PMID- 8216033 TI - Periodical gingival bleeding as a presenting symptom of periodontitis due to underlying cyclic neutropenia. Case report. AB - A 13-year-old boy presenting with spontaneous and periodical gingival bleeding accompanied by fever was thoroughly examined in order to determine the underlying aetiology of the gingival bleeding. Following repeated blood tests, the patient was diagnosed as having cyclic neutropenia. Thus, it was suggested, gingival bleeding, especially when spontaneous and periodical, should be carefully investigated to eliminate the possibility of cyclic neutropenia. PMID- 8216034 TI - An unusual primary first molar impaction associated with a supernumerary tooth. Case report. AB - A case of an impacted primary first mandibular molar associated with a supernumerary tooth is described and illustrated with radiographs. A brief discussion of the findings and therapeutic considerations is presented. PMID- 8216035 TI - Hypochlorite injury to the lip following injection via a labial perforation. Case report. AB - This report documents ulceration of the oral aspect of the lip, with facial swelling, following injection of Milton's solution into the lip through a labial perforation of tooth 13. After palliative therapy the ulceration healed within six weeks, and paraesthesia within three months. PMID- 8216036 TI - Coronal morphology of the mandibular second premolar in the Singaporean Chinese. AB - Five hundred and sixty-four patients of Singaporean Chinese origin with bilateral second premolars present were screened. Morphological features of the crown, number and position of cusps and the sex of the patient were recorded. The mesio distal dimensions of the crowns were measured. Three hundred and seventy-four (66.3 per cent) exhibited bilateral 2-cusp forms; 143 (25.4 per cent) were 3-cusp forms; and 47 (8.3 per cent) were mixed. There was no sex predilection in the three groups. In the 2-cusp forms, the predominant occlusal pattern was H-shaped (75.9 per cent). The 3-cusp type with a Y-shaped pattern and a squarish outline is a significant morphological and racial characteristic in the local population. The presence of 2-cusp and 3-cusp forms in an individual is an unusual developmental phenomenon. PMID- 8216037 TI - Orofacial sensitivity reactions and the role of dietary components. Case reports. AB - Dietary components have proven to be important aetiological factors in orofacial sensitivity reactions such as plasma cell gingivitis and orofacial granulomatosis. The use of elimination diets to identify these dietary antigens can be instrumental in both diagnosis and effective treatment for these disorders. PMID- 8216038 TI - Oral herpes remission and fluoride pulsing. Case reports. AB - Based on evidence from observation of some twenty cases, there would appear to be a relationship between the incidence and severity of herpes simplex attacks and the ingestion of daily fluoride in the form of tablet supplementation. Although only anecdotal at present, the cases presented seem to indicate that children who had previously suffered from recurrent herpes entered into a period of partial or complete remission when receiving daily fluoride tablet supplementation. Further observations are needed to confirm this relationship. PMID- 8216039 TI - One-year clinical evaluation of three dentine bonding agents. AB - One hundred and twenty-five composite restorations were placed in non-undercut, non-enamel-etched Class V abrasion lesions in 20 patients using the dentine bonding agents Scotchbond 2, Tripton, and Prisma Universal Bond 2. Patients were recalled at approximately 3 months, 6 months, and 1 year. After 1 year the cumulative per cent survival of restorations was Scotchbond 2, 8 per cent; Scotchbond 2 with dentine roughening, 16 per cent; Tripton, 16 per cent; Prisma Universal Bond 2, 75 per cent. PMID- 8216040 TI - The evolution of the complete denture base. Theories of complete denture retention--a review. Part 2. AB - The history of denture base materials and the accompanying development of impression techniques are traced from the earliest times to the present day (Part 1) as a prelude to a study (Part 2-4) of the various theories that have been advanced to explain retention of the base without mechanical support. These theories are critically reviewed and tabulated in chronological order. Some areas for further investigation are identified. PMID- 8216041 TI - Study of gypsum-bonded casting investments. Part 2. AB - The simultaneous differential thermal analysis--thermogravimetry (DTA-TG) method used in Part 1 of this two-part study was extended to analyse two gypsum-bonded dental casting investments, Kerr Cristobalite Inlay and GC Cristobalite Micro. Both investments had a similar cristobalite content of about 70 per cent. The remaining 30 per cent was dental stone in GCM, and a mixture of plaster and dental stone in KCl. Inclusion of plaster in KCl appeared responsible for the greater amount of water required for mixing this investment. The DTA-TG method used in the present study can be applied to identify the type and amount of hemihydrate, and the type of silica, in currently available gypsum-bonded investments. PMID- 8216042 TI - Australian Dental Research Fund Trebitsch Scholarship. An assessment of the permeability of dental protective gloves. AB - Several overseas studies have documented the presence of defects in unused latex and vinyl gloves. Since such defects compromise the barrier protection afforded by gloves, information regarding the frequency and site of defects which occur during manufacture is of direct clinical relevance. This study utilized a four stage testing procedure to evaluate defects in 13 brands of gloves which are used commonly in dental practice in Australia. Macropores in unused gloves were a significant problem, with 10 brands containing 1 per cent or more defective gloves. In addition, variations in electrical conducitivity, signifying microporosity or inconsistencies in thickness, were also observed. These findings indicate that there is room to improve further the quality of protective gloves. PMID- 8216043 TI - Dentistry at the crossroads--where to now? PMID- 8216044 TI - Neuro-otological findings in patients with spinocerebellar degeneration: with special regard to the duration of illness. AB - Neuro-otological findings in 150 patients with spinocerebellar degeneration were analyzed based on the duration of illness since onset. The results of each kind of neuro-otological examination varied in close relation to the duration of illness. Also, the results of each kind of examination correlated closely. In particular, the optokinetic nystagmus test and the visual suppression test correlated most closely. Neuro-otological examinations were confirmed to be of great value in gauging progression in spinocerebellar degeneration. PMID- 8216045 TI - Immunocytochemical localization of copper-zinc superoxide dismutase in mouse olfactory mucosa. AB - Copper-zinc superoxide dismutase (Cu-Zn SOD) has been localized in mouse nasal mucosa. Immunocytochemical staining using polyclonal antibody against Cu-Zn SOD revealed endogenous Cu-Zn SOD in sustentacular cells in the olfactory area, and in ciliated epithelial cells in the respiratory area of the olfactory mucosa. Since these cells are located in the superficial portion of the olfactory mucosa, Cu-Zn SOD may serve as an intracellular antioxidant. PMID- 8216046 TI - Can Rouviere's lymph nodes in non-malignant subjects be identified with MRI? AB - The lateral retropharyngeal lymph nodes lie between the carotid artery and prevertebral muscles. These are most obvious anterior to the arch of C1, but can be seen to the level of the soft palate. The uppermost-positioning nodes anterior to the atlas are called as the nodes of Rouviere. Introduction of CT and MR has provided us the chance to detect them. In order to find out the frequency of identifying them in normal subjects, I examined axial MR images which had been taken for the last 3 years. A total of 90 patients (86 adults and 4 children) with a variety of diseases except for malignancies were selected. All 4 children showed Rouviere's nodes bilaterally, while only 5 of 86 adults (5.8%) depicted them. The lymph nodes were identified as isointense masses as nasopharyngeal lymphoid tissues (adenoids), when presented, with the size ranged from 4 to 13 mm. The nodes with a diameter of 5 mm or more were easily identified particularly with T2-weighted images. The benign reactive adenopathy appeared indistinguishable from that demonstrated in patients with malignant tumors in the head and neck. PMID- 8216047 TI - Mucosal folds of eustachian tube in young children. AB - Differences in the extent of mucosal folding in the superior versus the inferior half of the human Eustachian tube (ET) were studied in young children by measuring the length of the mucosal margin and counting the number of mucosal folds, as they appeared in histological cross-sections, in the pharyngeal, midcartilaginous, isthmus, and osseous portions of each half of the ET in 12 normal ET/temporal bone specimens from 12 individuals aged 1 day to 2 years. The mucosal margin of the ET was significantly longer in the inferior half than in the superior half in the pharyngeal, midcartilaginous, and isthmus portions (paired t-test, pharyngeal portion: t[11] = 3.71, p < 0.01; midcartilaginous portion: t[11] = 4.52, p < 0.01; isthmus portion: t[11] = 3.40, p < 0.01). However, there was no significant difference between in the inferior half and in the superior half at the osseous portion. Also there were significantly more mucosal folds in the inferior half than in the superior half in all four portions (paired t-test, pharyngeal portion: t[11] = 3.46, p < 0.01; midcartilaginous portion: t[11] = 7.40, p < 0.01; isthmus portion: t[11] = 5.03, p < 0.01; osseous portion: t[11] = 4.49, p < 0.01). These results indicate that the surface area of the mucosa in the inferior half of the ET is larger than that of the superior half.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216048 TI - Sex hormones in juvenile nasopharyngeal angiofibroma tissue. AB - Five cases of juvenile nasopharyngeal angiofibroma were studied in terms of the presence of progesterone, estradiol, testosterone, and dihydrotestosterone in the juvenile nasopharyngeal angiofibroma tissue using the peroxidase-antiperoxidase method. Progesterone and estradiol were positive in all cases. Testosterone was positive in 2 of the 5 patients. Dihydrotestosterone was positive in 3 of the 5 patients. Hormone in the juvenile nasopharyngeal angiofibroma tissue seems to change by the activity of nasopharyngeal angiofibroma. PMID- 8216049 TI - Estradiol and testosterone in minor salivary glands of Sjogren's syndrome. AB - Nine patients with Sjogren's syndrome were studied in terms of estradiol, testosterone, and dihydrotestosterone in the labial minor salivary glands using the peroxidase-antiperoxidase method. In normal controls in women, estradiol was positive in the epithelial cells of duct, but testosterone and dihydrotestosterone were negative or doubtfully positive by case. Thus, it seems that there is a sex difference of receptors in the ductal epithelia. In the labial minor salivary glands of the patients, all estradiol, testosterone, and dihydrotestosterone were positive. As the background of Sjogren's syndrome, it seems that there is an influence of sex hormones. PMID- 8216050 TI - Malignant tumors of the head and neck in young patients. AB - Ten patients under 20 years of age, with malignant tumors of the head and neck was treated at the Department of Otorhinolaryngology of Kitasato University Hospital from August 1971 to December 1989. The primary lesions were situated in the nose and paranasal sinuses in 3, middle ear in 2, epipharynx in 2, and parapharynx, esophagus, and neck in 1 patient. Histological examination indicated 3 rhabdomyosarcomas, 2 malignant lymphomas, and 1 each of neuroblastoma, malignant neuroendocrine tumor, transitional cell carcinoma, lymphepithelioma, and squamous cell carcinoma. The sites of origin and histopathology of malignant tumors in such patients usually differ from those in adults. Well differentiated squamous cell carcinoma of head and neck is common in adults but not in children, in whom non-epithelial malignant tumors or sarcomas are not rare. Radiotherapy is more effective for treating malignant tumors of the head and neck in young than in adults. Eight of 10 patients are still alive, 7 of whom for 5 years or more. Two with rhabdomyosarcoma died. PMID- 8216051 TI - Clinical analysis of steroid-responsive sensorineural hearing loss. AB - In order to clarify general clinical features, characteristics of hearing level fluctuation, and therapeutic strategy in steroid-responsive sensorineural hearing loss, we conducted clinical analysis in the cases which were registered based upon the diagnostic criteria proposed by Kanzaki in 1981. The results obtained were as follows: (1) Disregarding steroid-responsiveness, both ears were impaired in all cases. (2) Female predominance and middle aged onset were found. (3) The underlying immunological abnormality could exist even in the cases without systemic autoimmune disease. (4) The mean incidence in acute hearing change was about once a year in low-frequency area and once 2 years in mid- and high frequency areas. (5) The mean value of maximum hearing level fluctuation during follow-up period was about 35 dB. (6) The final prognosis of hearing was relatively excellent. (7) By the supplemental administration of Sairei-to for more than 2 years, the maintenance dose of prednisolone was reduced in 80% of the subjects without any significant deterioration of hearing. PMID- 8216052 TI - Biofeedback therapy in the treatment of tinnitus. AB - Seven patients were treated with electromyographic biofeedback therapy for intractable tinnitus which was supposed to be reinforced by mental distress and muscle tension. Three patients, who succeeded in decreasing electromyographic levels of the frontal muscle, were able to reduce tinnitus and relieve anxiety. One patient could eliminate tinnitus only during biofeedback sessions, but the efficacy was not continuous in daily life. The other three patients, who failed to decrease electromyographic levels, did not obtain favorable results. It is suggested that biofeedback therapy appears to be of greatest benefit when muscle tension and mental distress are the cause of magnification of the tinnitus symptoms. PMID- 8216053 TI - Bioethics nursing network. PMID- 8216054 TI - Enterprise bargaining and the nursing industry. PMID- 8216055 TI - WA welcomes Latvian nurses. PMID- 8216056 TI - Transcultural emphasis in NT education. PMID- 8216057 TI - The health labour force. Part 3 of health care economics. PMID- 8216058 TI - Hospital waiting lists: fact or fiction. PMID- 8216059 TI - Living related hepatic donation: Prometheus or Pandora's box? PMID- 8216060 TI - Laparoscopic appendicectomy: a prospective analysis. AB - The potential advantages of laparoscopic surgery for a number of abdominal operations including appendicectomy have been heralded. In this study the aims were to assess prospectively the role of routine diagnostic laparoscopy in the diagnosis of acute appendicitis and determine the efficacy of laparoscopic appendicectomy. Patients with suspected acute appendicitis had diagnostic laparoscopy. When the diagnosis was confirmed laparoscopic appendicectomy was performed. Where an alternative diagnosis was made the appropriate treatment was instituted. If no diagnosis could be made the macroscopically normal appendix was removed by laparoscopic appendicectomy. Eighty-one patients (50 female, 31 male) had an initial diagnostic laparoscopy; 53 had appendicitis and proceeded to laparoscopic appendicectomy. A diagnosis could not be established at diagnostic laparoscopy in six patients and they also proceeded to laparoscopic appendicectomy. An alternative diagnosis was made in the remaining 22 patients (19 female and 3 male), with five proceeding to laparotomy and one patient with mesenteric adenitis having laparoscopic appendicectomy. Seven patients having laparoscopic appendicectomy required conversion to an open operation due to a retrocaecal or perforated appendix. The median operating time for successful laparoscopic appendicectomy was 55 min (range 30-95). Morbidity occurred in five of 53 patients having a successful laparoscopic appendicectomy. The median postoperative hospital stay was 2 days. The median time before return to normal activities was 8 days. Diagnostic laparoscopy is a useful diagnostic technique in women with suspected acute appendicitis, as it improves diagnostic accuracy, reduces the negative appendicectomy rate and avoids unnecessary laparotomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216062 TI - Bile duct cysts: presentation in adults. AB - Bile duct or choledochal cysts are rare congenital anomalies and presentation in adult is infrequent. Seven cases of type I/IV bile duct cysts presenting in adult life have been treated by the authors during the past 2 years. The diagnosis was made using a combination of ultrasound and cholangiography (endoscopic retrograde cholangiopancreatography/percutaneous transhepatic cholangiography). All cases underwent total cyst excision and Roux-en-Y hepaticojejunostomy. There were no operative complications and all patients were asymptomatic in the follow-up period, which ranged from 3 to 23 months. PMID- 8216061 TI - The operative aetiology and types of adhesions causing small bowel obstruction. AB - Postoperative adhesions account for 64-79% of admissions with small bowel obstruction (SBO). The aim of this study was to identify the operative procedures and the types of adhesions that cause SBO. A retrospective analysis of all patients with an admission diagnosis of acute adhesive SBO between January 1982 and December 1990 was performed. One hundred and nineteen patients had 144 admissions with an initial diagnosis of acute SBO due to adhesions. The previous operations were: appendicectomy 23.3%; colorectal resection 20.8%; gynaecological surgery 11.7%; upper gastrointestinal (gastric, biliary or splenic) surgery 9.2%; small bowel surgery 8.3%; and more than one previous abdominal operation 23.6%. Sixty-one admissions required surgery to relieve the SBO. Eighteen patients had strangulated small bowel. All but two of these patients had a single band adhesion causing the SBO and associated strangulation. Band adhesions were commonly found following appendicectomy, colorectal resections or gynaecological operations. Seventeen of the 21 patients with previous surgery for a colorectal malignancy had benign adhesions causing the SBO, while four of the six patients with either previous ovarian or previous gastric carcinoma had recurrent malignancy causing the SBO. Five patients had previously undiagnosed carcinomas (three ovarian and two caecal) as the cause of the SBO. PMID- 8216063 TI - Percutaneous insertion of long-term venous access catheters via the external iliac vein. AB - Long-term venous access using Hickman catheters and implantable subcutaneous ports is a well established technique. These devices have customarily been inserted via the internal jugular, subclavian or cephalic veins. On occasions, these routes may be unavailable. This article reviews the outcome of 53 prolonged venous access catheters (39 Hickmans and 14 catheters attached to implantable ports) inserted percutaneously via the external iliac vein into 37 patients over a period of 5.7 years. The indications for insertion were chemotherapy (40%), total parenteral nutrition (36%), intravenous antibiotics (13%), poor venous access (7%) and bone marrow transplantation (4%). The main reasons for use of the external iliac vein were thrombosis of the subclavian veins or superior vena cava and subclavian central line sepsis. The only complication of insertion was one inadvertent puncture of the external iliac artery. Twenty-seven catheters (51%) remained complication free and functioning for the time for which they were required. Four catheters (7%) are still functioning in situ having been present for 1-5 years. Sixteen catheters (30%) became infected, with a 17% incidence of septicaemia. Venous thrombosis was associated with three catheters (6%). Catheters remained in situ for a median period of 30 days (range 5-569 days). The authors conclude that long-term venous access using percutaneous external iliac vein insertion is a useful technique when other routes are unavailable, but there is a relatively high incidence of catheter-related sepsis. PMID- 8216064 TI - Comparison of percutaneous with intra-operative balloon angioplasty for arteriosclerotic occlusive disease. AB - The purpose of this study was to compare the technical success and short-term outcome of intraoperative balloon angioplasty (IBA) with percutaneous transluminal angioplasty (PTA) in the iliac and femoropopliteal segment. From January 1988 to February 1991, 99 consecutive patients underwent 114 angioplasties in the iliac (37 PTA, 26 IBA) and femoropopliteal segment (15 PTA, 36 IBA). Mean age and sex distributions were similar between the groups. Claudication was the primary indication for both groups. All patients who underwent IBA had another concomitant surgical procedure performed. Immediate technical success for PTA and IBA were 50/52 (96%) and 58/62 (94%), respectively. Cumulative patency up to 12 months following angioplasty of the iliac artery was 94% for PTA and 78% for IBA (P-value NS). For the femoropopliteal segment, 12 month patency results were 100% for PTA and 78% for IBA (P-value NS). Complications requiring surgical intervention occurred in 3 (6%) PTA and 5 (8%) IBA cases. Results from this study indicate that technical success and early patency are similar for PTA and IBA in the iliac and femoropopliteal segments. However angioplasty-related complications were not avoided by performing balloon angioplasty in the operating room. PMID- 8216065 TI - Evaluation of 242 consecutive parotidectomies performed for benign and malignant disease. AB - Between 1987 and 1992, one surgeon performed 242 parotidectomies in 229 patients. Among 97 patients with benign disease, pleomorphic adenoma (46) and sialo adenitis (28) predominated, while metastatic melanoma (22) and squamous cell carcinoma (21) were the most common diagnoses among 132 patients with malignancy. The extent of parotidectomies were: 114 'appropriate' resections, 77 complete superficial parotidectomies, 35 near-total conservative and 14 radical total resections. The facial nerve was sacrificed in 19 operations and reconstructed in four. One hundred and five patients had a concomitant neck dissection and 45 patients had adjuvant radiotherapy. Postoperative facial nerve function was normal in 90% of patients with localized tumours and 55% of patients overall. Patients with sialo-adenitis or deep lobe tumours and those having a neck dissection were at greatest risk of facial weakness despite nerve preservation. At a median follow up of 34 months, 13 patients had developed tumour recurrence and attempts at salvage surgery have generally been disappointing. PMID- 8216066 TI - Surgical thyroid disease in Papua New Guinea. AB - A clinical and histopathological analysis was carried out on 376 thyroid specimens removed under various diagnoses from the surgical clinics of Papua New Guinea over a period of 11 years (1980-90). Solitary nodular goitre (solid and cystic) was the most common clinical diagnosis. Nineteen per cent of the solid and 35% of the cystic solitary nodular goitres were found to be malignant. Malignant goitres were confirmed histologically in 73.3% of the clinically diagnosed cases of malignancy. The presence of amyloid goitre (1.9%) posed a significant diagnostic and therapeutic problem due to its clinical features resembling that of malignant goitre. Hemithyroidectomy (lobectomy) was the most common surgical procedure employed for all unilateral thyroid lesions and partial or subtotal thyroidectomy was performed for benign and most malignant lesions. PMID- 8216067 TI - Use of polyglyconate suture in paediatric gastrointestinal anastomosis. AB - The perfect suture has been defined, but in certain circumstances some features are more important than others. In paediatric gastrointestinal surgery lack of tissue drag is of great importance. Because the life expectancy of most paediatric patients having gastrointestinal operations is measured in many decades, and the long-term effects of retained suture materials are relatively undocumented, absorbability is also of importance. A polyglyconate copolymer suture (Maxon, Davis & Geck, Gosport, UK) has undergone trial. It is a monofilament absorbable suture. It has a low coefficient of friction, very low tissue drag and is stronger (straight pull and knot strength) than corresponding gauges of braided synthetic absorbable sutures. It is slowly absorbed, its half life (in relation to strength) being 5 weeks and complete disappearance occurring in 6-7 months. The trial was prospective and randomized. All members of the Department of Surgery at the Children's Hospital, Camperdown participated. Sixty five anastomoses were performed in 56 patients. All varieties of joins were performed (oesophageal, duodenal, small and large bowel, and biliary-enteric). There were no statistically significant differences in the result in terms of outcome and complications. Overall handling and tissue drag were assessed by the surgeon at the end of the operation on a visual analogue scale and analysis of these results showed no significant difference in overall handling, but significantly less tissue drag (unpaired t-test). It is concluded that Maxon is superior to other currently available sutures for paediatric gastrointestinal surgery. PMID- 8216068 TI - Laparostomy: a technique for the management of severe abdominal sepsis. AB - The mortality from acute suppurative peritonitis may approach 70%, survivors often undergoing multiple operations and requiring protracted intensive medical support. Attempts to improve prognosis fail when they rely on the diagnosis of persistent or recurrent collections. The results of laparostomy in conjunction with continuous peritoneal irrigation (CPI), which aims to primarily eradicate and subsequently prevent the recurrence of sepsis are reported. Two deaths occurred in this series of seven patients, only one attributed to persistent sepsis. Overall, the mortality of 28% compares favourably with similar patient series and suggests that laparostomy with CPI deserves consideration in the management of selected patients with severely contaminated abdominal cavities. PMID- 8216069 TI - Vaginography: the investigation of choice for vaginal fistulae? AB - Adequate demonstration of the pathology and site of vaginal fistulae is preferable before surgical intervention is planned. Vaginal fistulae have traditionally been investigated by upper and lower gastrointestinal contrast radiology, often with a failure to demonstrate the fistula. The authors' recent experience confirms that vaginography is a simple and accurate method of assessing many types of vaginal fistulae. PMID- 8216070 TI - Do medical students remember multiple choice questions? AB - The values of pre-testing senior medical students at the start of their surgical terms are the perception that they acquire of the scope of the subject and the extra practice they gain in the technique of sitting multiple choice question (MCQ) exams. The purpose of this study was to determine whether MCQ in a pre-test that were repeated in a post-test were answered more accurately than questions that had not been repeated. For the past 3 years at the University of Queensland, fifth year medical students have been voluntarily sitting pre- and post-tests in each of the four surgical terms. Each examination consisted of 60 clinically oriented surgical questions of a difficulty appropriate for senior medical students. A total of 404 students did both the pre- and post-tests during 1990 and 1991. The two examinations were carefully chosen for comparability. Of the 60 questions in each examination, 30 were repeated in the post-test and 30 were fresh questions in the post-test. The pre- and post-tests were reversed for the second of the two years to increase consistency. There was a general improvement in the standard of results from the pre-test to the post-test. There was also a small improvement for the repeated questions compared to the non-repeated questions (P < 0.0001). The authors conclude that the marked improvement of the post-test compared to the pre-test is mostly attributable to the students increasing their knowledge base through learning during their surgical term.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216071 TI - Spontaneous regression of osseous metastasis in renal cell carcinoma. AB - A case of spontaneous regression of an osseous metastasis in renal cell carcinoma is presented. The extreme rarity of this phenomenon, especially in this location, is pointed out, as only three other cases have been published so far. PMID- 8216072 TI - Gastric outlet obstruction secondary to a gallstone in the duodenal bulb. PMID- 8216073 TI - Splenic trauma following colonoscopy. PMID- 8216074 TI - Massive epistaxis from traumatic aneurysm of the internal carotid artery. AB - Intracavernous carotid artery aneurysm following head injury is a rare occurrence. Two such cases presenting with delayed but massive and repeated epistaxis are reported and the literature reviewed. The first case required a trapping procedure while the second case had only cervical carotid ligation to control the bleeding. Both resulted in no neurological sequelae. PMID- 8216075 TI - Closed flexor tendon rupture in the palm: an unusual but predictable clinical entity. AB - Closed intratendinous ruptures of flexor tendons are uncommon. Two such cases that occurred within the lumbrical origin are reported. Accurate history taking and clinical examination usually enable the site of rupture to be determined. Ultrasound examination can also help to localize the site. The role of the lumbrical, extrinsic flexors and trauma in the aetiology of the rupture are discussed. PMID- 8216076 TI - Intussusception complicated by gangrene, demarcation and separation of the appendix. PMID- 8216077 TI - Plant poisoning? Which plant?! PMID- 8216078 TI - Risks of fish imports--the 1993 aquatic animal quarantine review. AB - The rapid expansion of knowledge of fish diseases and pathogens in the past decade has led to a realisation that Australian quarantine policy on fish imports, which has largely evolved on a needs basis, requires substantial revision. As a result, the Australian Quarantine and Inspection Service has commissioned a major review of quarantine policy with regard to risks of disease associated with importation of aquatic animals and their products. The review, to be managed by the Bureau of Resource Sciences, will be carried out this year. PMID- 8216079 TI - Gonadotrophin-releasing hormone treatment in cattle: a meta-analysis of the effects on conception at the time of insemination. AB - Data from 40 trials described in 27 published papers were analysed by meta analysis (pooling of data from numerous trials into a single analysis) to evaluate the effects of injecting gonadotrophin-releasing hormone (GnRH) in cattle at the time of insemination on the risk of pregnancy. A total of 19,019 cows were involved in these studies. Analyses were stratified by trial and by the effects of dose of GnRH, type of GnRH and insemination number (first, second or third and greater). Mantel-Haenszel analysis revealed that use of GnRH at insemination significantly increased the overall risk of pregnancy by 12.5% in treated cows (P < 0.05). However, increases in risk of pregnancy were greatest (22.5%) when repeat breeders were tested. Results for use of GnRH or analogue at first service were similar, with increased risks of pregnancy in treated cows of 5.2 and 8.0%, respectively. The risk of pregnancy tended to be higher (11.1%) when the dose of GnRH was > or = 250 micrograms and when used at second insemination (9.9%). The analyses demonstrated that while treatment at insemination with GnRH and GnRH analogues increased conception rates in dairy cattle, some variation in study results was attributable to the number of inseminations after calving at which GnRH is administered. Further efforts should be made to determine characteristics of populations of cows that have good fertility responses to GnRH and to determine the mode of action of GnRH in increasing fertility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216080 TI - The development of high synthetic pyrethroid resistance in Bovicola (Damalinia) ovis and the implications for resistance management. AB - A field strain of the sheep body louse, Bovicola (Damalinia) ovis, was tested in vitro against a range of synthetic pyrethroids (SP) and demonstrated a degree of resistance 80 to 900 times that of a susceptible strain. The dose response of this strain was compared with that of other strains showing low and intermediate resistance. These data, and those from other reported cases suggest that SP resistance in sheep lice develops sequentially through a low level stage with resistance factors of 20 or less. Further selection results in the development of strains with resistance factors of up to several hundred. The implication is that preventing or managing resistance requires proper lice control management including choosing a chemical capable of eradicating lice populations. PMID- 8216081 TI - The efficacy of injectable and pour-on formulations of moxidectin against lice on cattle. AB - The efficacy of one administration of moxidectin against natural infestations of the 3 common species of cattle lice in Australia: Linognathus vituli, Damalinia bovis and Haematopinus eurysternus, was determined. A high degree of control of L vituli (the long-nosed sucking louse) was achieved with both the cattle injection (96.7% and 100%) at 0.2 mg/kg and the cattle pour-on formulation (94.6% and 100%) at 0.5 mg/kg on the 2 farms where this louse occurred. An injection of moxidectin at 0.2 mg/kg did not eliminate D bovis. In these trials efficacy ranged from nil to 85.2%. In contrast the pour-on formulation at 0.5 mg/kg provided consistently high efficacy (83.6 to 100%) against D bovis on 3 farms. Infestations of H eurysternus (the short-nosed sucking louse) were low and no significant difference was recorded between treatment groups in a single trial, however, lice persisted on 3 to 7 cattle in the untreated group at each inspection, whereas none were found on any animals in the 2 groups treated with moxidectin on inspection after treatment. PMID- 8216082 TI - Experimental acute yellow-wood (Terminalia oblongata) intoxication in sheep. AB - An aqueous suspension of air-dried, hammer-milled leaf of Terminalia oblongata (yellow-wood) was administered to sheep by gavage, as a single dose of 5 to 20 g (dry weight)/kg body weight. Doses of 15 g/kg, or more, caused depression, inappetence, abdominal pain and reduced ruminal movements within 24 to 48 h and some sheep also showed dyspnoea, opisthotonus and champing of the jaws. Haematology and blood gas and acid-base measurements were unaffected. In sheep given a dose of 12.5 g/kg, or more, plasma osmolality, aspartate aminotransferase activity and potassium and bilirubin concentrations increased while plasma total protein markedly decreased and plasma sodium concentration and alkaline phosphatase activity remained normal. Most sheep were necropsied 48 h after dosing. The liver showed zonal hepatocellular necrosis, the pattern of which varied with the dose given. No renal lesions were observed, although one sheep given a very high dose became azotaemic and hyperkalaemic. Hydrothorax, hydropericardium and ascites developed in sheep given doses of 15 or 20 g/kg. PMID- 8216083 TI - Treatment of feline hyperthyroidism using orally administered radioiodine: a study of 40 consecutive cases. AB - Forty cats with hyperthyroidism were treated using 200 to 300 (typically 250) MBq [corrected] of orally administered 131I. Thirty-six cases (90%) were successfully treated, as assessed by resolution of clinical signs and reduction in plasma thyroxine concentrations to normal or reduced values after treatment. Although higher doses of 131I appear to be required when the radioisotope is administered orally rather than intravenously, a less stressful administration procedure and greater availability of therapy capsules offer useful advantages for treating thyrotoxic cats. PMID- 8216084 TI - Prevalence of the causes of fleece derangement among sheep flocks in New South Wales. AB - An investigation of sheep flocks with unknown histories of fleece derangement, selected at random from the main sheep raising areas of New South Wales, showed that Psorergates ovis was present in 53 of the 177 flocks surveyed and in 162 of the 3495 sheep examined. Of the single causes of fleece derangement, the most prevalent was grass seed contamination (15.7%) followed by infestation with sheep body lice, Bovicola ovis, (14.7%) and infestation with itch mite (7.8%). The prevalence of fleece derangement was significantly higher on sheep in which lice were the only ectoparasites found than on those in which itch mites were the only ectoparasites present. The greatest prevalence of P ovis was in flocks in the Young, Yass, Mudgee and Tenterfield districts. In most affected flocks, more than one potential cause of fleece derangement was present. Itch mite infestation was more prevalent in flocks that received no treatment for ectoparasites than in those that had been treated in the year preceding the survey. Our results did not support a commonly held belief among farmers that arsenical compounds control infestations of itch mites more effectively than other types of pesticides. There was no significant difference in prevalence of fleece derangement between flocks treated with different pesticide groups and those that received no treatment, but mean fleece derangement score was significantly lower in sheep treated with organophosphates than in untreated sheep. Infestations of lice were significantly more prevalent in sheep from flocks treated with synthetic pyrethroids than from those treated with organophosphates or those that received no treatment. PMID- 8216085 TI - Leukoencephalomalacia in horses. PMID- 8216086 TI - Diagnosis of botulism in cattle using ELISA to detect antibody to botulinum toxins. PMID- 8216087 TI - Pathogenicity of Acholeplasma oculi for the sheep udder. PMID- 8216088 TI - Isolation of bluetongue virus serotypes 1, 21 and 23 from healthy sentinel cattle in Irian Jaya, Indonesia. PMID- 8216089 TI - A comparison of two preparations of 'swormlure-2' in a bait for screw-worm flies. PMID- 8216090 TI - Chronic locomotor dysfunction, associated with a thalamic-cerebellar neuropathy, in Australian merino sheep. PMID- 8216091 TI - Survival of platypuses in captivity. PMID- 8216092 TI - The Harold E Albiston Oration. PMID- 8216093 TI - The clinical biochemistry of experimentally produced lupinosis in the sheep. AB - Lupinosis was produced in sheep in four experiments by administering a toxic extract of Phomopsis leptostromiformis by various routes and at various dose rates. The course of the intoxication was followed by plasma biochemical analyses for a number of electrolytes, metabolites and enzymes. Results from these analyses suggested that in addition to being an hepatotoxicity, lupinosis also resulted in injury to muscle, kidney and adrenal cortex. This was confirmed by microscopic examination of these tissues. PMID- 8216094 TI - Chronic cryptosporidiosis in Australian elapid snakes: control of an outbreak in a captive colony. AB - An outbreak of chronic cryptosporidiosis resulting in hypertrophic gastritis occurred in a captive colony of Australian elapid snakes. Two species of the genus Notechis were involved: Notechis ater (Black Tiger Snake) and Notechis scutatus (Eastern or Mainland Tiger Snake). The infection was eventually fatal in all 9 affected snakes. Typical histopathological findings of the stomach included mucosal thickening with cystic dilatation of gastric glands, moderate oedema and fibrosis of the lamina propria, and a mild to moderate patchy infiltration of inflammatory cells. Procedures implemented to contain the outbreak included the use of a formaldehyde-based disinfectant, prompt removal of faecal matter, uneaten and regurgitated food from enclosures, and examination of faecal specimens for Cryptosporidium oocytes and other pathogens. PMID- 8216095 TI - Adrenalectomy of sheep: a novel technique. AB - A rapid technique for adrenalectomy of sheep was developed. Bilateral adrenalectomy was performed in a single stage operation by inducing ischaemia with latex rings of the type used commonly for the castration of lambs and calves. The success of the technique was demonstrated by failure of exogenous ACTH to increase circulating cortisol concentrations. Adrenal steroid replacement was used to maintain the sheep during the post-operative period (cortisol 0.25 mg.kg-1, deoxycorticosterone acetate 0.05 mg.kg-1). Adrenalectomised sheep were maintained for up to 20 days without glucocorticoid, provided a lowered dose of mineralocorticoid was administered (0.04 mg.kg-1 x day-1). Adrenalectomised sheep had significantly (P < 0.007) lower packed cell volume (23.75%) than normal sheep (31.24%), across a broad range of cortisol concentrations (0 to 734 ng/mL), indicating that plasma cortisol may not reflect true blood concentrations when drawing comparisons between adrenalectomised and normal sheep. PMID- 8216096 TI - Reproductive performance of thoroughbred mares on six commercial stud farms. AB - The records of 1630 mare years from 6 Thoroughbred stud farms in south eastern Australia were analysed for the years 1981 to 1986. Overall pregnancy and foaling rates were 83.9% and 69.3%, respectively. When calculated per served oestrous cycle, pregnancy and foaling rates were 54.7% and 43.1%, respectively. Pregnancy and foaling rates were higher (P < 0.001) for mares 3 to 10 years of age than for older mares. There was no difference in the pregnancy rates of maiden, barren and foaling mares. The foaling rate was significantly higher (P < 0.001) in mares that became pregnant during the first served oestrous cycle (77.8%) than in mares that needed two served oestrous cycles to become pregnant (65.4%). Of all diagnosed pregnancies, 19.5% were not completed. Pregnancy loss was lower (P < 0.05) in maiden (12.4%) than in barren (19.7%) or foaling (20.9%) mares. Twins were diagnosed in 7.8% of all pregnancies. If one conceptus was lost without external interference, 84.1% of pregnancies went to term. If one conceptus was manually crushed, 55.9% of pregnancies were maintained. If prostaglandin was used to terminate twin pregnancies, 60% of mares so treated produced foals the following year. PMID- 8216097 TI - Rhodococcus equi-associated osteomyelitis in foals. AB - Two cases of Rhodococcus equi infection in foals are described, in which osteomyelitis was a feature. Because rhodococcal infection is usually low grade and chronic, and because the signs of early metaphysitis can be subtle, any articular or periarticular swelling in a foal from a farm with a history of rhodococcosis should be strongly suspected to be associated with R equi until proven otherwise. PMID- 8216098 TI - Treatment with ivermectin of sarcoptic mange in pigs. AB - Ivermectin injectable solution (1% w/v) was highly effective against Sarcoptes scabiei var suis when administered subcutaneously once to swine at 300 mcg/kg body weight. There were significantly (P < 0.05) fewer Sarcoptes mange mites counted on pigs treated with ivermectin than on untreated pigs at each count up to day 56 after treatment. The results indicate ivermectin should provide an efficient, practical means of control of sarcoptic mange in intensive piggeries. PMID- 8216099 TI - Renal failure in a koala. PMID- 8216100 TI - Renal complications of cystitis in koalas. PMID- 8216101 TI - Pyrrolizidine alkaloid poisoning of yaks: diagnosis of pyrrolizidine alkaloid exposure by the demonstration of sulphur-conjugated pyrrolic metabolites of the alkaloid in circulating haemoglobin. PMID- 8216102 TI - Reactivity of dogs and cats to feeding fleas and to flea antigens injected intradermally. PMID- 8216103 TI - Gestational diabetes and follow-up among immigrant Vietnam-born women. AB - Gestational diabetes is associated with an increased risk of fetal macrosomia and perinatal death. Immigrant mothers from Vietnam who delivered in the Mercy Hospital for Women between January 1, 1979 and December 31, 1990 were investigated to assess their risk of gestational diabetes, the factors that were associated with gestational diabetes, and the prevalence of diabetes mellitus on follow-up. These mothers were compared with Australian-born mothers attending the same hospital and who delivered in the same period. Using a logistic regression model, gestational diabetes was found to be more common in Vietnam-born mothers who were older, who were primigravidas, or were underweight and the risk of gestational diabetes increased over the time period of the study. The adjusted relative risk of gestational diabetes for Vietnam-born women was 1.43 (95% confidence limits 1.10, 1.86) compared with Australian-born women. The incidence of gestational diabetes was 7.8% (144 of 1,839) in Vietnam-born mothers and 4.3% (1,173 of 27,086) in Australian-born mothers. Vietnam-born mothers also had a greater risk of diabetes mellitus on follow-up; 25% (17 of 68) of those with follow-up testing had developed diabetes mellitus within 9 years of diagnosis of gestational diabetes, in comparison with an incidence of 9% (52 of 581) of Australian-born mothers with follow-up testing. Vietnam-born mothers should have glucose tolerance testing performed during pregnancy to detect gestational diabetes and those diagnosed should have long-term follow-up to detect the development of diabetes mellitus. PMID- 8216104 TI - Why do Asian-born women have a higher incidence of gestational diabetes? An analysis of racial differences in body habitus, lipid metabolism and the serum insulin response to an oral glucose load. AB - We have observed a higher incidence of gestational diabetes (GDM) in Asian-born than in Caucasian women. Body habitus, serum lipid levels and the serum insulin response to a glucose load in pregnancy were compared in 15 women with normal glucose tolerance, 16 Caucasian women with GDM and 19 Asian-born women with GDM. Caucasian women with GDM, unlike Asian-born women with GDM, were obese compared with control women as measured by body mass index (p = 0.022). Both groups of GDM women had similar patterns of insulin response to oral glucose with a delayed insulin peak and an elevated 2-hour insulin level (p = 0.0021). In addition, the insulin response per unit of glycaemic stimulus (incremental insulin area/incremental glucose area at 1 hour) was reduced in both GDM groups (p = 0.035). Fasting serum triglyceride levels were higher in women with GDM although this was only significant in the Caucasian group (p = 0.014). Asian-born women with GDM had significantly lower (p = 0.041) serum cholesterol levels than Caucasian women with GDM. There was a significant correlation (p = 0.025) between glucose tolerance (area under the curve) and fasting serum triglyceride values. The relationship between lipid and carbohydrate metabolism in Asian-born and Caucasian women in pregnancy requires further investigation. PMID- 8216105 TI - The influence of a glucose load on subsequent carbohydrate metabolism in pregnancy. AB - Two separate independent exercises comparing 50 g with 75 g and 100 g oral glucose tolerance tests (OGTT) were performed in Chinese pregnant women. We found a significant difference in fasting values between the paired OGTTs when the 100 g test preceded the 50 g test. The fasting glucose levels on the second occasion of testing were significantly lower than on the first testing. The difference was less pronounced when the first glucose load was 75 g and was insignificant when the 50 g test was given first. The blood glucose response to glucose loads was also significantly altered on the second occasion of testing, again in proportion to the size of the first glucose load. We postulate that this influence of glucose tolerance testing on subsequent carbohydrate metabolism results either from sensitization of the pancreatic islet cells or from sensitization of tissues, resulting in increased rate of glucose utilization. We also suggest that an 1,800 Kcal diet represents an increase in carbohydrate load over their normal diet for many of our patients. In patients with mildly deranged OGTT, improvement in the glucose profile on diet may be due to this phenomenon rather than to a decrease in carbohydrate as is believed. PMID- 8216106 TI - Standard parameters of preeclampsia: can the clinician depend upon them to reliably identify the patient with the HELLP syndrome? AB - Four hundred and fifty-four gravid women were identified with the HELLP syndrome from January, 1980 to May, 1992. The peak systolic and diastolic blood pressures, proteinuria, and uric acid were recorded for each patient during the peripartal course. Patients were classified according to disease severity with, in addition to elevated lactate dehydrogenase (LDH) values, laboratory evidence of haemolysis and hepatic dysfunction, a peripartal platelet count < or = 50,000/microliters was depicted Class I, Class II as a platelet count > 50,000 and < or = 100,000/microliters and Class III as > 100,000 and < or = 150,000/microliters. Patients with Class I HELLP syndrome had peak antepartum systolic blood pressures < 150 mm Hg significantly more often than the Class II (p < 0.0091) or Class III (p < 0.04) HELLP syndrome. Class I HELLP syndrome had significantly more patients with 1+ to 2+ proteinuria than Class II (p < 0.02) and Class III HELLP syndrome (p < 0.009). Uric acid levels were not different among nor proportionately related to increasing severity of the HELLP syndrome. PMID- 8216107 TI - Corticosteroids for the enhancement of fetal lung maturity: impact on the gravida with preeclampsia and the HELLP syndrome. AB - This study was undertaken to determine maternal impact of corticosteroids administered for the promotion of fetal lung maturity in mothers with the HELLP syndrome. Twenty-seven of 427 women with the HELLP syndrome treated between 1980 1991 received a full course of steroids prior to preterm delivery. This group was compared to 27 matched control patients with the HELLP syndrome who received no corticosteroids. Subjects were matched for maternal age, race, sex of the fetus, and severity of the HELLP syndrome. The antepartum platelet count stabilized or increased in 25 of 27 steroid-treated women in contrast to 0 of 15 control women (p < 0.00001). In comparison to control patients, LDH serum concentrations in steroid-treated patients stabilized or decreased and the SGOT/AST and SGPT/ALT stabilized or decreased during therapy (p < 0.005). The interval from delivery to platelet nadir in patients with Class III HELLP syndrome was shorter in the steroid-treated group (p < 0.008) than in untreated patients. PMID- 8216108 TI - Corticosteroids for enhanced fetal lung maturation in patients with HELLP syndrome: impact on neonates. AB - This study was undertaken to determine retrospectively, in women with the HELLP syndrome, the perinatal effects of corticosteroid administration for promotion of fetal lung maturity. Twenty-seven of 427 women with the HELLP syndrome treated between 1980 and 1991 received a full course of steroids prior to preterm delivery. They were compared to 27 control patients with the HELLP syndrome matched for maternal age, severity of disease, gestational age, race, and sex of the fetus. Respiratory distress requiring mechanical ventilation occurred in 13 of 27 neonates who received steroid administration and in 23 of 27 who did not receive steroids (p < 0.001). The average stay in the neonatal intensive care unit was 29.8 +/- 50.6 days for the steroid-treated group and 45.2 +/- 35.3 days for the group without steroid use (p = NS). The incidence of neonatal deaths, intraventricular haemorrhage type III and IV, necrotizing enterocolitis, and retrolental fibroplasia was greater in the control group but the difference was not statistically significant. PMID- 8216109 TI - Prenatal diagnosis of hypoplastic left heart syndrome. AB - Over a 21-month period 200 fetal echocardiographic studies were performed on pregnancies at high risk for congenital heart disease referred to the NSW Fetal Echocardiography Service. Four cases of hypoplastic left heart syndrome were diagnosed in-utero during this period. These cases demonstrated the heterogeneity of this lesion, its known association with other defects and chromosomal anomalies, and evidence of in-utero evolution. Hypoplastic left heart syndrome is reliably diagnosed by fetal echocardiography. This lesion is heterogenous and may evolve beyond the first trimester. Careful attention to ventricular function, endocardial echoes and Doppler flow may assist with diagnosis. PMID- 8216110 TI - Normal ranges for Doppler flow velocity waveforms from maternal uterine and fetal umbilical arteries. PMID- 8216111 TI - Ultrasound fetal weight estimation: precision or guess work? AB - We compared the prediction of birth-weight based on factors shown by epidemiological studies to influence it with the performance of 2 clinical examples of ultrasonic fetal weight estimation reported in the literature. The standardized absolute error of the 2 examples of ultrasonic fetal weight estimation was similar to estimation by multiple regression of birth-weight on maternal age, parity, height and weight in 11,516 Chinese mothers. This severely limits the clinical utility of the estimation derived from these ultrasonic measurements. PMID- 8216112 TI - The predictive value of abnormal fetal heart rate patterns in early labour. AB - An abnormal early intrapartum cardiotocogram was found to have a sensitivity of 26.4% and a positive predictive value of 28.3% for the detection of fetal acidaemia at birth and a sensitivity of 27.3% and a positive predictive value of 3.3% for the prediction of 5-minute Apgar scores below 7. The presence of meconium in the liquor amnii improved the predictive properties of the test. Although an abnormal early intrapartum feta heart rate pattern indicated a higher risk group, the majority of patients with abnormal early intrapartum cardiograms had a favourable outcome. A normal pattern does not exclude an adverse outcome. PMID- 8216113 TI - Term breech delivery: does X-ray pelvimetry help? AB - Over a 3-year period a retrospective audit was performed of all uncomplicated singleton breech presentations at term to assess the role of X-ray pelvimetry. The review included 267 term breech presentations. Seventy-seven women (Group A) delivered in a consultant unit where X-ray pelvimetry was not used for decision making regarding the mode of delivery; 125 women (Group B) delivered in 2 consultant units where X-ray pelvimetry was always used, and 65 women (Group C) delivered in a fourth consultant unit where X-ray pelvimetry was used selectively. Obstetric outcome was measured in terms of mode of delivery. Short term neonatal outcome was assessed by Apgar score at 5 minutes, evidence of birth trauma and admission to the neonatal special care unit for more than 24 hours. Significantly fewer women (12.9%) had an elective Caesarean section in group A compared with the other 2 groups (27.2% in group B and 33.8% in group C; p < 0.05). The vaginal delivery rates following a trial of labour were not significantly different (79.1% for group A, 65.9% for group B and 65.1% for group C) and neonatal outcome was similar in all groups. It is concluded that fewer Caesarean sections were done, without adversely affecting the neonatal outcome, when X-ray pelvimetry was not used to select the mode of delivery of uncomplicated singleton breech presentation at term. Satisfactory progress in labour is the best indicator of pelvic adequacy. PMID- 8216114 TI - A comparison of abdominal and vaginal examinations for the diagnosis of engagement of the fetal head. AB - The diagnosis of engagement of the fetal head is mandatory before operative vaginal delivery is to be attempted. There is widespread belief that the fetal head is engaged in the maternal pelvis when vaginal examination reveals that the bony presenting part has reached the level of the ischial spines. However, it is also claimed that in the presence of moulding the vaginal findings may be misleading and that it may be preferable to make the diagnosis by abdominal examination of the level of the fetal head in relation to the pelvic brim. In order to evaluate the relative merits of each of these 2 systems of physical examination, a retrospective study was made of 104 cases which had been evaluated for possible operative vaginal delivery by both methods. Prediction of successful vaginal delivery was greater by abdominal criteria (94%) than by vaginal criteria (80%) (p < 0.01). When evaluated by maximum likelihood logistic regression analyses, the factor of greatest importance in determining the probability of allocation of a case to each of the engagement groups was moulding (odds ratio 2.17; 95% confidence intervals 0.75-6.27). We conclude that when these 2 methods of assessment produce different diagnoses, the major factor responsible is moulding of the fetal head. Clinical evaluation prior to operative vaginal delivery must include abdominal examination and reliance on vaginal findings alone may prove misleading when moulding is present. PMID- 8216115 TI - Induction of labour: does internal tocography result in better obstetric outcome than external tocography. AB - A prospective randomized study was undertaken to evaluate the benefit of intrauterine catheters in induced labour. Two hundred and thirty nine women who had induced labour were studied. The patients in one group had intrauterine catheters inserted and oxytocin was titrated to achieve the 75th percentile of uterine activity observed in spontaneous normal labour according to parity. Contractions were assessed by external tocography in the other group and oxytocin was titrated to achieve 6 to 7 contractions per 15 minutes each lasting > 40 seconds. Mean maximum dose of oxytocin, mode of delivery, Apgar score < 7 at 5 minutes, cord arterial blood pH < 7.15 and admission to neonatal intensive care unit did not differ significantly in the 2 groups. In conclusion, women who had intrauterine catheters did not have a shorter duration of labour, lower dose of oxytocin, fewer operative deliveries or fewer babies in poor condition at birth compared with those who had external tocography in induced labour. PMID- 8216116 TI - Predilatation of the cervix in first trimester termination of pregnancy. A comparative study of the prostaglandin analogue, 16,16 dimethyl-trans-delta 2 PGE1, methyl ethyl ester (Cervagem) and mechanical dilatation. PMID- 8216117 TI - Pregnancy complicated by maternal phenylketonuria. AB - Pregnant women who have elevated levels of serum phenylalanine are more likely to have a spontaneous abortion or to give birth to an infant with congenital cardiac anomalies, symmetrical growth retardation, microcephaly and mental retardation than pregnant women with normal levels of this amino acid (1). Nine pregnancies in 7 women were managed in conjunction with the staff of the Children's Hospital, Sydney. In 6 patients, satisfactory serum levels of phenylalanine were attained and 6 offspring are all normal at follow-up, ranging from 15 years to 1 year. The 2 children of the poorly controlled mother were of low birth-weight and both had microcephaly at birth. The poor control of serum phenylalanine was due to poor compliance with the strict dietary regimen. It is concluded that dietary control of serum phenylalanine levels below 600 umol/l in pregnant women with PKU is possible and desirable and may improve perinatal and long-term outcome. This requires close co-operation between paediatrician, dietician, obstetrician and patient. Further data are required to confirm these findings in larger numbers and to provide long-term neurological follow-up. PMID- 8216118 TI - A New South Wales population-based study of stillbirths weighing 2,500 g or more. AB - This paper describes factors associated with singleton stillbirths weighing 2,500 g or more, born in 1987 and reported to the NSW Midwives' Data Collection (MDC), a statewide perinatal data collection system. A total of 136 singleton stillbirths in this weight range were notified to the MDC, representing one quarter of all singleton stillbirths in NSW. MDC records on these stillbirths were linked with perinatal death registrations for 125 of the 136. The death registrations indicated that fetal death occurred during labour in 20 cases, prior to the onset of labour in 98, and at an unknown time in the remaining 7 cases. Placental complications, including haemorrhage and functional abnormalities of the placenta, were the most frequent group of conditions associated with the stillbirths, being recorded as the underlying cause of death in 42 (34%) of the 125 cases. Cord complications (such as cord compression or cord around the neck) were given as the underlying cause of death in 30 cases (24%). The death certificate diagnosis was confirmed by autopsy in only 27 of the 125 cases (22%), although autopsies may have been done on a further 45 cases (36%). An adequate explanation of the cause appeared to be lacking for many of the fetal deaths. This highlights the importance of a thorough and systematic investigation of stillbirths. A list of standard investigations to be carried out following a stillbirth is proposed. PMID- 8216119 TI - Heterosexual transmission: a growing risk factor for HIV spread. AB - The risk of human immunodeficiency virus (HIV) spread by heterosexual contact is emerging as a risk factor for women in Sydney in the 1990's. As shown by this study, heterosexual exposure to the virus accounted for 40% of women in Western Sydney acquiring the disease between 1989-1991 inclusive, compared with 0% in 1982-1985 inclusive. Further public awareness of this mode of transmission and information on safe sex practices is necessary to limit the spread of the AIDS virus. PMID- 8216120 TI - Comparison of cytology and cervicography in screening a high risk Australian population for cervical human papillomavirus and cervical intraepithelial neoplasia. AB - Two different screening methods, the Papanicolaou (Pap) smear and cervigram were compared in screening 245 Sydney women over a 6-month period in 1988 at a city sexually transmitted diseases (STD) centre, for cervical human papillomavirus (HPV), cervical intraepithelial neoplasia (CIN) and cervical cancer. The Pap smear through the identification of cytologically abnormal cells correctly detected 54% of cases of histologically proven CIN and 39.2% of cases of HPV. The cervigram through the identification of acetowhite epithelium and/or abnormal vessels on the cervix correctly detected 64% of cases of histologically proven CIN and 70.6% of cases of HPV. However, when both tests were used together, 92% of CIN lesions and 82.4% of HPV lesions were correctly identified. Histology of a colposcopically directed biopsy was used as the 'gold standard'. The sensitivity and specificity of the Pap smear after correction for verification bias was 46% and 78% respectively, and for the cervigram was 49% and 60% respectively. Hence neither screening test appears adequate on its own, at least in an STD population. PMID- 8216121 TI - Detection of human papilloma virus (HPV) infection in paraffin-embedded tissues of endometrial carcinoma. AB - Although human papilloma virus (HPV) associated lesions constitute a well recognized clinical entity in the female lower genital tract, namely vulva, vagina and cervix, few studies have demonstrated HPV infection in other genital sites, particularly in the ovary and uterine corpus. Recently, with the highly sensitive polymerase chain reaction (PCR) technique, HPV infections were found in an ovarian tumour and adenocarcinoma of the cervix. This prompted a retrospective analysis of HPV DNA in 22 cases of endometrial adenocarcinoma in order to investigate the possible carcinogenesis of HPV in the uterine corpus. In this study DNA extraction was performed from paraffinized cancerous tissues and the normal cervical counterpart. HPV 6, 11, 16 and 18 primers specific oligonucleotides were used in PCR to detect the presence of this oncogenic virus. HPV 16 DNA was found in 1 endometrial adenocarcinoma and 4 cervical tissues. Our result did not support the aetiological role of HPV in the carcinogenesis of endometrial carcinoma. PMID- 8216122 TI - Intrauterine insemination with husband's sperm: comparison of pregnancy rates in couples with cervical factor, male factor, immunological factor and idiopathic infertility. AB - Intrauterine insemination with husband's sperm (IUI) is offered to couples with infertility due to various causes although there is no general agreement on which of these causes should be so treated. In this report 77 couples were diagnosed as having either cervical factor, male factor, immunological factor or unexplained infertility. Insemination was performed 24-32 hours after a rapid rise in the serum LH level. Two of 16 pregnancies which resulted miscarried, 1 was ectopic and the remainder were full term. Eleven occurred in the cervical factor group, 3 in the immunological factor and only 1 in each of the male factor and unexplained infertility groups. The differences in the number of pregnancies between the cervical factor and male and unexplained infertility groups are significant but not between the groups with cervical and immunological factors. The majority of pregnancies (81%) were achieved in the first 4 cycles. Patients with the cervical factor as the cause of their subfertility are likely to benefit from the IUI with their husband's sperm. The small number of patients with the immunological factor in this study does not allow for a conclusion. In our experience the male factor and unexplained infertility patients are unlikely to benefit from intrauterine insemination with husband's sperm. PMID- 8216123 TI - Withdrawal from a donor insemination programme. AB - The aim of this study was to examine the factors that influenced the withdrawal of couples from a regional donor insemination programme. Demographic, medical, treatment and outcome data were prospectively recorded on 375 referrals. One hundred and eight women had conceived at least 1 normal pregnancy. Withdrawals from the programme, without pregnancy, accounted for 165 couples, whilst 47 had begun treatment, and a further 29 were on the waiting list. Thirty nine (24%) of those withdrawing did so without notice or reason. Most of these (33) were in couples waiting to begin treatment. Natural conception, adoption, identifiable medical or social reasons (including separation) and moving to another region were the predominant causes for withdrawing. Women who had entered the programme because of their partner's oligospermia had a high natural conception rate. Age, socioeconomic status, geographic location and length of infertility did not affect the withdrawal rate. PMID- 8216124 TI - Laparoscopic treatment of ectopic pregnancy. PMID- 8216125 TI - The role of operative laparoscopy in the management of infertility. PMID- 8216126 TI - The value of vaginal ultrasound in the management of menorrhagia. AB - Vaginal ultrasonography has been carried out on 97 patients with menorrhagia who were either not responding to or not suitable for drug therapy. Ultrasonography demonstrated normal uteri in 33, benign uterine enlargement in 4, bicornuate uteri in 2, intracavitary polyps or fibromyomas in 9, possible adenomyosis in 13 and intramural or subserous fibromyomas in 36. The ultrasound diagnosis markedly increased the accuracy of clinical diagnosis and assisted in the proper choice of treatment which included the avoidance of surgery and the selection of patients most suited to endometrial resection, intrauterine resection of polyps and fibromyomas, and open or laparoscopic myomectomy and hysterectomy. The routine use of high resolution vaginal ultrasound in the management of menorrhagia is recommended. PMID- 8216127 TI - Menopause before 40--premature, but not always permanent. AB - Seventy-five women with premature menopause presented to a reproductive endocrinologist over a 3-year interval. Thirty-five had an identifiable cause, usually a chromosomal defect, autoantibodies or cytotoxic chemotherapy. Forty had no apparent cause and of this group 5 conceived on hormone replacement therapy (HRT). Overall, this group of oestrogen deficient women had spent nearly half of their menopausal years to date, not on HRT. PMID- 8216128 TI - Septic pelvic thrombophlebitis: an unusual treatable postpartum complication. AB - Septic pelvic thrombophlebitis is an uncommon but serious postpartum complication occurring in about 1 in 2,000 pregnancies, characterized by pain, antibiotic resistant fever and tachycardia. In about 50% of cases a pelvic mass is present which is usually right-sided (especially when the ovarian vein is involved). It is estimated to cause 18 maternal deaths per million pregnancies in the United States. Use of contrast enhanced CT scanning and a trial of heparin therapy increases the diagnostic certainty. It is particularly important because surgical management which may otherwise be suggested because of a spiking fever and a mass seems to be associated with a poorer prognosis than does conservative management. PMID- 8216129 TI - Haematoma complicating fetal intravascular transfusions. PMID- 8216130 TI - Anti-Kell in pregnancy and hydrops fetalis. PMID- 8216131 TI - Cellular uterine myoma causing vaginal bleeding in a 15-year-old girl. PMID- 8216132 TI - Limitations of CA125 in the preoperative evaluation of a pelvic mass: struma ovarii and ascites. AB - This report discusses the limitations of using the serum tumour marker CA 125 in the preoperative evaluation of a woman presenting with a pelvic mass. We present 2 cases of benign struma ovarii which were associated with elevated levels of CA 125. PMID- 8216133 TI - Comparing 2 local anaesthetic techniques for outpatient hysteroscopy. PMID- 8216134 TI - The potential hazards of the birthing frame. PMID- 8216135 TI - Decline in cervical cancer screening. PMID- 8216136 TI - Haematometra--a complication of endometrial ablation. PMID- 8216137 TI - Study of prescription drugs in the first trimester and congenital malformations. PMID- 8216138 TI - Assessments of astronaut effectiveness. AB - This study examined the reliability and convergent validity of three methods of peer and supervisory ratings of the effectiveness of individual NASA astronauts and their relationships with flight assignments. These two techniques were found to be reliable and relatively convergent. Seniority and a peer-rated Performance and Competence factor proved to be most closely associated with flight assignments, while supervisor ratings and a peer-rated Group Living and Personality factor were found to be unrelated. Results have implications for the selection and training of astronauts. PMID- 8216139 TI - Communication between space crews and ground personnel: a survey of astronauts and cosmonauts. AB - A total of 54 astronauts and cosmonauts returned questionnaires which addressed several aspects of communication between space crews and ground personnel. Two factors were rated as significantly helping this communication: Shared Experience and Excitement of Space Flight. Two additional factors were judged to significantly hinder space-ground communication: Spacecraft Ambient Noise and Space Sickness. Respondents also significantly endorsed the value of contact with loved ones on Earth as having a positive influence on mission performance, particularly cosmonauts and long-duration space travelers. The need for a private space-ground transmission link was mentioned by several respondents. There was no consensus as to whether or not negative personal information should be withheld until the space crew returned to Earth, although some respondents indicated that this might be justified during short-duration as opposed to long-duration missions. These findings have important scientific and operational implications for future manned space missions. PMID- 8216140 TI - Flying after diving and decompression sickness. AB - Reports of 1,159 decompression sickness (DCS) incidents during recreational diving were analyzed by logistic regression for the effects of flying on the occurrence of Type II DCS, complete relief of symptoms after one recompression, and residual symptoms 3 months after treatment. The relevant diver populations were those who: 1) did not fly; 2) had symptoms before flying but flew anyhow; 3) and did not have symptoms before flying but developed symptoms during or after flight. Of the total DCS population, 13.9% had preflight symptoms while 5.6% developed symptoms during or after flight. Symptoms which occurred during or after flight were no more serious and their responses to recompression no less successful than symptoms in nonflying divers. There was a statistically significant association between divers who flew with pre-existing symptoms and Type II DCS, incomplete relief with one recompression, and residual symptoms after 3 months. PMID- 8216141 TI - Breathing 100% oxygen compared with 50% oxygen: 50% nitrogen reduces altitude induced venous gas emboli. AB - The risk of venous gas emboli (VGE) and decompression sickness (DCS) must be determined before selection of the lowest pressure for an extravehicular activity (EVA) pressure suit which eliminates the requirement for prebreathing. In earlier studies, use of a 50% oxygen:50% nitrogen breathing mixture (50:50 mix) during 139 zero-prebreathe decompressions of male subjects to 8.3-7.8 psia resulted in 51 instances of severe VGE and one case of DCS. Our current study investigated effects of 40 zero-prebreathe decompressions of male subjects to 8.3-6.8 psia for 6 h while breathing 100% oxygen and performing moderate exercise. No DCS symptoms were observed. Severe VGE were not detected at 8.3 psia, but were present during 10%, 20%, and 40% of the exposures at 7.8, 7.3, and 6.8 psia, respectively. Zero prebreathe decompression while breathing 100% oxygen results in significantly lower VGE and DCS risk levels than while breathing a 50:50 mix. Our results show that 7.3 psia EVA pressure suits with 100% oxygen should be safer than 8.3 psia suits with a 50:50 mix. PMID- 8216142 TI - Autonomic physiological data associated with simulator discomfort. AB - A physiological monitoring capability was developed for the Army's Crew Station Research and Development Facility (CSRDF), a research simulator for advanced rotorcraft. Preliminary physiological data are reported from studies of simulator induced sickness. Our objective was to demonstrate sensitivity of physiological measures relative to self-reports of simulator sickness severity. The data suggested that heart period, tachygastria, and skin conductance level were more sensitive to simulator sickness than were vagal tone and normal myoelectrical gastric activity. PMID- 8216143 TI - Changes in compensatory eye movements associated with simulated stimulus conditions of spaceflight. AB - Compensatory vertical eye movement gain (CVEMG) was recorded during pitch oscillation in darkness before, during and immediately after exposures to the stimulus rearrangement produced by the Preflight Adaptation Trainer (PAT) Tilt Translation Device (TTD). The TTD is designed to elicit adaptive responses that are similar to those observed in microgravity-adapted astronauts. The data from Experiment 1 yielded a statistically significant CVEMG decrease following 15 min of exposure to a stimulus rearrangement condition where the phase angle between subject pitch tilt and visual scene translation was 270 degrees; statistically significant gain decreases were not observed following exposures either to a condition where the phase angle between subject pitch and scene translation was 90 degrees or to a no-stimulus-rearrangement condition. Experiment 2 replicated the 270 degrees-phase condition from Experiment 1 and extended the exposure duration from 30 to 45 min. Statistically significant additional changes in CVEMG associated with the increased exposure duration were not observed. The adaptation time constant estimated from the combined data from Experiments 1 and 2 was 29 min. PMID- 8216144 TI - Chinese hyper-susceptibility to vection-induced motion sickness. AB - Little is known about the factors that control individual differences in susceptible to motion sickness. A serendipitous observation in our laboratory that most Chinese subjects become motion sick prompted this study. We used a rotating optokinetic drum to provoke motion sickness and compared gastric responses and symptom reports of Chinese, European-American, and African-American subjects. There was no difference in the responses of European-American and African-American subjects; however, Chinese subjects showed significantly greater disturbances in gastric activity and reported significantly more severe symptoms. We suggest that this hyper-susceptibility presents a natural model for the study of physiological mechanisms of nausea and other symptoms of motion sickness. PMID- 8216145 TI - Salt loading test in a population adapted to moderately high altitude living (3,000 m). AB - The sodium excretory capacity of normal subjects acutely mobilized from sea level to moderately high altitude was compared to native subjects adapted to high altitude living (3,000 meters). This study was conducted in order to provide insights into hormonal adaptations associated with acute mobilization to a hypoxemic environment and to try to determine how these variables could influence the renal handling of a salt load. A standard amount of 5% NaCl solution at a volume of 100 ml/m2 BSA was infused over a 30-min period to all subjects. Urine collections were obtained periodically over the next 3 h. Subjects adapted to moderately high altitude living were able to excrete a salt load faster than unadapted subjects (57.1 vs. 32.9 mmol.m-2.h-1, respectively). No change in plasma atrial natriuretic factor (ANF) concentration in either group of subjects was observed during the salt administration period. Adapted individuals had significantly higher baseline levels of antidiuretic hormone (ADH). The high altitude natives enhanced excretory response to a salt load was not explained by any observed hormonal changes and their lack of increased ADH release to serum osmolar changes was unexplained. PMID- 8216146 TI - Effects of orthostatic and anti-orthostatic stress on patent and stenotic coronary arteries in swine. AB - Head-up tilt (HUT) followed by head-down tilt (HDT) has been used to simulate the acute phase of adaptation to microgravity. This study evaluates the effects of HUT and HDT on the coronary circulation before and during coronary stenosis. Seven pigs were placed in the prone position and exposed to the following orientations for 20 min each: 1) 0 degrees horizontal (HZ); 2) +70 degrees HUT; and 3) -15 degrees HDT. The swine were then placed in the HZ position for 20 min while hemodynamics returned to baseline. The diameter of the left anterior descending (LAD) coronary artery was reduced to a point slightly less than that which produced a decrease in blood flow and the protocol was repeated. Heart rate (HR), contractility (dP/dt), mean arterial blood pressure (MABP), left ventricular pressure (LVP), coronary sinus pressure (CSP), left-ventricular end diastolic pressure (LVEDP), coronary blood flow (CBF), coronary vascular resistance (CVR), myocardial oxygen consumption (MVO2) and coronary sinus lactate were determined after 20 min in each position. The transition from HUT to HDT elicited a significant (p < 0.05) increase in MABP, LVP, CSP, LVEDP, MVO2, and CBF and a significant decrease in CVR. During HDT, MVO2 increased 20 +/- 10% from Hz and 68 +/- 15% from HUT. There was a comparable increase in coronary artery flow. The hemodynamic responses were not significantly altered during pneumatic coronary occlusion. However, coronary sinus lactate was significantly elevated in the HDT positions. This study demonstrates a substantial increase in CBF during HUT to HDT with and without coronary stenosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216147 TI - F-16 pilot experience with combat ejections during the Persian Gulf War. AB - Most experience with ejections from modern fighter aircraft has occurred outside of true combat operations. During Operation Desert Storm, the 401st Fighter Wing, Torrejon Air Base, Spain, lost four F-16C aircraft while on combat missions, with all four pilots ejecting safely. Since the circumstances of a combat vs. peacetime ejection are likely different and many combat mishaps and ejections cannot be extensively investigated (three out of these four), a questionnaire was developed to recall and review pilot ejection experiences. Questions ranged from recalling the parameters of egress to conscious recollections of the event and assessment of how well the system worked. Each of the four ejections occurred under different parameters, and no one suffered significant injury. Two of the ejections occurred at high altitude, previously rare in the F-16. This was one of the first times that experience was obtained with the F-16's ACES-II egress system under combat operations and, in the experience of these four pilots, the system was life-saving in combat. Finally, the overall ejection survival rate for U.S. Air Force fighter/attack combat ejections during Operation Desert Storm was similar to the peacetime rate. It is the author's hypothesis that the reason for this may correlate with a quicker, more predetermined decision to eject from an aircraft disabled by combat fire. PMID- 8216148 TI - Aircrew fatigue during Desert Shield C-5 transport operations. AB - The metrics used to define U.S. Air Force crew rest and flight duty limitations were not designed to manage surge operations such as Operation Desert Shield. Desert Shield provided an opportunity to obtain inflight data on acute and cumulative fatigue and the effect of other stressors during over-the-shoulder observations on 24 C-5 airlift crew members. Findings emphasize how sleep history, recent duty day cycles, subjective fatigue, scheduling patterns, nutrition, and billeting facilities contribute to fatigue and lower levels of alertness. The results of this fairly insignificant observational study attempt to preserve some of the aeromedical lessons of Desert Shield. The flight surgeon authors integrate their experience to outline development of a fatigue management and alertness enhancement doctrine. PMID- 8216149 TI - Helicopter rotor blade injury: a persistent safety hazard in the U.S. Army. AB - Rotor blade injuries are an inherent hazard of helicopter operations. To determine the recent incidence of rotor blade injuries in the U.S. Army, a review of accident records (1972-91) was conducted. Crash-related injuries were not included. During the study period, there were 24 blade strike injuries (12 involving the main rotor), 11 (46%) of which were fatal. Comparison with previous reports indicates a lower rotor blade injury rate in the last decade than in any previous period. The head was injured most frequently (65%), followed by the chest (17%) and abdomen (7%). Protective helmets helped to reduce injury in several instances. Flight crew comprised 49% of the victims, passengers 29%, ground crew 14%, and bystanders 8%. Helicopter crews must maintain situational awareness when around turning blades--professional training alone does not guarantee protection from rotor blade injury. PMID- 8216151 TI - The greening of the medical profession. PMID- 8216150 TI - The oxygen window and decompression bubbles: estimates and significance. AB - The "oxygen window" causes a partial pressure difference of inert gas between the inside and outside of decompression bubbles. Estimates of Po2 and Pco2 in tissue are necessary for O2 window calculations and any calculations about growth or decay of decompression sickness bubbles, but the estimates involve many uncertainties. Using simplifying assumptions, we estimated the O2 window over a broad range of environments for tissues having a wide range of O2 extractions. The results were as follows: a) the window increases with ambient pressure, but levels off at very high pressure; b) the window is only 1 or 2 kPa for air breathing at extreme altitudes, and 200 kPa or more in hyperbaric environments; c) when O2 is breathed instead of air, the window is as much as 50 times larger at altitude but only about 10 times larger in hyperbaric environments; d) changes in bubble size due to the window decrease as barometric pressure increases; and e) there are seven additional factors which may supplement or oppose the action of the oxygen window. PMID- 8216152 TI - Psychiatric diagnoses aboard an aircraft carrier. PMID- 8216153 TI - NASA joins industry in AIDS research. PMID- 8216154 TI - Use of advanced technology in distance education. PMID- 8216155 TI - Bicuculline administered into the amygdala blocks benzodiazepine-induced amnesia. AB - This experiment investigated the effect of intra-amygdala administration of the GABAergic antagonist bicuculline methiodide on benzodiazepine-induced amnesia. Male Sprague-Dawley rats were implanted bilaterally with cannulae aimed at the amygdala and allowed to recover for 1 week. Ten minutes before training in a continuous multiple trial inhibitory avoidance task a buffer solution or bicuculline methiodide (56 pmol/0.5 microliters) was injected bilaterally into the amygdala and this injection was immediately followed by a systemic injection of saline or midazolam (1.0 mg/kg). In comparison with saline controls, midazolam treated animals required more trials to reach the acquisition criterion of remaining in the starting chamber for 100 s. The midazolam effect on acquisition was not attenuated by intra-amygdala infusion of bicuculline methiodide, suggesting that the midazolam-induced changes in acquisition behavior do not involve the amygdaloid GABAergic system. On a 48-h retention test the performance of the midazolam-treated animals was significantly poorer than that of the controls. However, the retention performance of animals given intra-amygdala injections of bicuculline methiodide prior to the systemic injection of midazolam was comparable to that of the saline controls. These results suggest that the amygdaloid GABAergic system mediates the impairing effects of midazolam on retention of inhibitory avoidance training. PMID- 8216157 TI - Effects of age on water escape behavior and on repeated acquisition in rats. AB - The standard water escape task in a circular pool measures predominantly spatial reference memory (RM). We first tested 3- and 24-month-old Wistar rats (WISW:Bor) in the standard task. The RM performance of the 24-month-old animals was impaired in comparison to that of the 3-month-old rats. In a second experiment, we compared the performance of 24-month-old rats with that of 3-month-old animals, using the repeated acquisition paradigm originally described by Whishaw (Physiology and Behavior, 35, 139-143, 1985; Behavioral Brain Research, 24, 59 72, 1987). In this paradigm, the decrease in escape latency from the first to the second trial within trial pairs measures predominantly spatial working memory (WM). The young rats acquired the task within the first sessions. In contrast, the 24-month-old animals did not acquire the task, even after 12 daily training sessions. It is not clear, however, whether the poor performance of the old rats on the repeated acquisition task reflects impaired WM or whether they did not acquire the procedural aspects of the task. PMID- 8216156 TI - Evidence for state-dependent retrieval in conditioned place aversion. AB - State-dependent retrieval (SDR) in conditioned place aversion (CPA) was observed using Long-Evans male rats, with three different aversive drugs injected ip: lithium chloride (31.8 mg/kg), FG 7142 (10 mg/kg), and naloxone (5 mg/kg). Experiment 1 showed that state-dependent dissociation was complete with lithium chloride following two conditioning trials, but disappeared when the number of learning sessions was increased. Experiment 2 showed that following two conditioning trials, such complete state-dependent dissociations were also observed when FG 7142 or naloxone were used during conditioning. The results of this study showed that the expression of SDR is not monotonic in CPA paradigm but depends on the stage of learning. In addition, SDR can be observed following administration of a variety of drugs known to produce CPA, but differing in their neurochemical targets and the nature of the aversive effects they induce. Finally, these results are discussed with regard to what is known about SDR in other paradigms. PMID- 8216158 TI - Motion sickness in amphibians. AB - We explored the question of whether amphibians get motion sickness by exposing anurans (frogs) and urodeles (salamanders) to the provocative stimulus of parabolic aircraft flight. Animals were fed before flight, and the presence of vomitus in their containers after flight was used to indicate motion-induced emesis. None of the species that we studied vomited during the 8 to 10 parabolas of each flight. However, at least one specimen from each of the anuran species Rana rugosa, Rana nigromaculata, Hyla japonica, and Rhacophorus schlegelii vomited in a period of 0.5 to 42 h after flight. Some specimens of R. nigromaculata, H. japonica, and R. schlegelii were also observed retching without emesis either during or shortly after exposure to parabolic flight. We were unable to induce either emesis or retching behavior in the aquatic from Xenopus laevis. Among the urodeles studied we saw no signs of motion sickness in either adult or larval Cynops pyrrhogaster, but at least one larval Hynobius nebulosus vomited shortly after parabolic flight. The amphibian species that exhibited the most motion sickness were the same ones that showed the greatest amount of tumbling during the microgravity phases of their parabolic flights. The most distinctive difference between motion sickness in amphibians and mammals that vomit, including man, is the long delay between a provocative stimulus and emesis proper in the amphibians. The retching behavior we induced in the frogs was identical to that described previously for frogs treated with emetic drugs. H. japonica, exposed to extended periods of microgravity on the MIR Space Station, flattened their bellies against the substrate and dorsiflexed their heads in a manner reminiscent of drug-induced nausea. In light of our current observations of retching behavior in motion sick H. japonica, we suggest that the previously observed behavior of three frogs on the MIR Space Station was a manifestation of motion sickness. PMID- 8216159 TI - Age-related changes in correlation between behavioral and biochemical parameters in Lewis rats. AB - This study evaluated aging by using a correlational analysis of behavior and biochemistry in young (4 months old) and old (24 months old) Lewis rats. The rats were subjected to different learning tasks (spatial discrimination learning in the Morris task and cone-field task, temporal discrimination learning, one-trial inhibitory avoidance task) and noncognitive tests (emotional reactivity, motor coordination, and food motivation) and the relation between the various parameters was assessed. In the learning tasks, except for the inhibitory avoidance task, the first part of the learning curve was taken as an index of learning. Blood glucose (baseline and blood glucose regulation) and hippocampal choline acetyltransferase (ChAT) activity were also measured. There was no correlation between the different parameters of learning in young and old rats. This indicates that there are individual differences in performance in different learning and memory tasks. Measures of noncognitive behavior (food motivation, emotional reactivity, and motor performance) did not predict performance in the learning tasks. Hippocampal ChAT activity did not correlate with learning performance in old rats, whereas blood glucose level was found to correlate with spatial learning in old rats. These results suggest that an impaired regulation of blood glucose may be related to cognitive performance in aging. PMID- 8216160 TI - CGP 36742: the first orally active GABAB blocker improves the cognitive performance of mice, rats, and rhesus monkeys. AB - The learning capacity of experimental animals in cognitive tests can be improved by blockade of the GABAB receptors. After treatment with the GABAB antagonist CGP 36742, mice performed better in a passive-avoidance test; rats did likewise in a partner-recognition test, and rhesus monkeys also in a "conditional spatial color" task. The effects demonstrated in these three different species and covering diverse manifestations of learning and memory give reason to hope that this new active principle may prove therapeutically useful. PMID- 8216161 TI - Facilitation of memory storage by the acetylcholine M2 muscarinic receptor antagonist AF-DX 116. AB - Post-training administration of the acetylcholine muscarinic M2 presynaptic receptor antagonist AF-DX 116 (0.1-10.0 mg/kg, ip), facilitated 48 h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. AF-DX 116 did not increase the retention latencies of mice that had not received a footshock during training. The influence of AF-DX 116 (1 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by AF-DX 116 (1 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to AF-DX 116 treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training AF-DX 116 on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and AF-DX 116 (0.1 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of AF-DX 116 (0.1 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the activation of a muscarinic cholinergic presynaptic inhibitory mechanism, probably by increasing brain acetylcholine release, may modulate the activity of post-training processes involved in memory storage. PMID- 8216162 TI - Facilitation of a distributed shuttlebox conditioning with post-training epinephrine in rats. AB - Forty-two male Wistar rats were trained in a two-way active avoidance task during 5 consecutive days (10 trails/session). Immediately after each training session animals were given an injection, ip, of 0.1 mg/kg (EPI 0.1 group) or 0.05 mg/kg (EPI 0.05 group) of epinephrine, or vehicle (Vehicle group). Long-term retention was tested 20 days after the last acquisition session. Our results showed that the lower dose of epinephrine (0.05 mg/kg) led to a significant improvement of acquisition, compared with both the Vehicle and the EPI 0.1 group. On the long term retention session the level of avoidances in both EPI 0.05 and Vehicle groups was similar to that achieved on the last acquisition session, although differences between groups failed to reach statistical significance. Concerning the EPI 0.1 group, a significant increase in the number of avoidances was observed between the last acquisition session and the long-term retention session. This later result might suggest that the higher dose of epinephrine would need a longer period to manifest its effectiveness. We conclude that the facilitatory effects of epinephrine are dose-dependent, and that under a distributed paradigm epinephrine modulates memory consolidation processes leading to an improvement of the magnitude of learning rather than merely speeding up learning. PMID- 8216163 TI - Endogenous opioids: a proximate reward mechanism for kin selection? AB - The kin selection theory predicts that individuals would behave differently toward one another, depending on their genetic relatedness. Proximate mechanisms have been postulated to exist helping the individual to discriminate what is good or bad for him. Opioids have been discovered to be involved in the mediation of reinforcement, in particular they underlay social emotion. In this study it is shown that pain sensitivity decreased in male mice interacting with siblings following 2 months of separation; this analgesic response was antagonized by naloxone administration. Interaction with unknown and unrelated subjects did not change the nociceptive threshold. These results suggest that interacting with kin is an adaptive situation reinforced, at the neural level, by the release of endogenous opioids. PMID- 8216164 TI - On the role of the hippocampus in learning and memory in the rat. AB - An overview of lesion experiments concerned with the involvement of the hippocampus in learning and memory in the rat is presented. Multiple injections of small amounts of ibotenic acid were used to selectively remove the hippocampus (dentate gyrus, hilar cells, CA1-CA3 pyramidal cells). Similar selective, axon sparing ibotenate lesions of hippocampus were used in a series of learning and memory experiments employing tasks that are thought to be important in hippocampal function. The performance of rats with the hippocampus removed was compared with that of control animals in the acquisition and retention of spatial versus nonspatial information, forgetting of spatial and nonspatial information, contextual learning, recognition memory and concurrent discrimination learning, and complex representational learning (conditional discrimination and negative patterning learning). The general finding that rats without a hippocampus were impaired on those tasks that required the utilization of spatial and contextual information stands in contrast with the spared performance that was found in learning about and handling (even complex) nonspatial information. Rather than support for views that emphasize a role for the hippocampus in specific memory processes (working memory, declarative memory, temporary memory buffer, configural learning), the present results are more compatible with the idea that the hippocampus plays an especially important role in processing and remembering spatial and contextual information. The limited data that are available using more selective lesions of related hippocampal formation structures (entorhinal cortex, subiculum) suggest that these structures also make important contributions to learning and memory, and that some of these contributions may be different from those made by the hippocampus. PMID- 8216165 TI - A simple (or simplistic?) cognitive model for schizophrenia. AB - An approach which views schizophrenia as a disturbance of information processing appears promising as a way of linking biological and clinical aspects of the disorder. A review of research in this area led to the suggestion that the basic disturbance in schizophrenia is "a weakening of the influences of stored memories of regularities of previous input on current perception". This formulation leads to the prediction that in certain circumstances, schizophrenics may perform better than normal subjects. Recent studies employing tasks derived from human experimental psychology provide evidence in support of the model. It is argued that the link between information processing disturbances and biological abnormalities may be facilitated by the use of paradigms derived from animal learning theory (latent inhibition and Kamin's blocking effect). On both tasks the pattern of performance of acute schizophrenics is consistent with the cognitive model. The ways in which such an information processing disturbance may lead to schizophrenic symptomatology are outlined, with particular reference to the formation and maintenance of delusional beliefs. The core cognitive abnormality may result from a disturbance in any of the brain structures involved in the prediction of subsequent sensory input. The proposed circuit, which draws heavily on Gray's model, implicates in particular the hippocampus and related areas and is consistent with studies of brain pathology in schizophrenia. PMID- 8216166 TI - Prediction of pain in patients with chronic low back pain: effects of inaccurate prediction and pain-related anxiety. AB - This study investigated predictions of pain intensity, reports of pain and anxiety, frequency of pain-related anxiety symptoms, and range of motion, in 43 patients exposed to pain during a physical examination. All patients had primary complaints of low back pain. The pain stimuli used for this study included back and/or leg pain produced by repeatedly raising the extended leg of the patient to the point of pain tolerance. Generally, findings demonstrated that (a) predictions of pain were a function of discrepancies between previous predictions and experiences of pain, (b) patients reporting greater pain-related anxiety showed a tendency to overpredict new pain events, but corrected their predictions readily, (c) patients reporting less pain-related anxiety displayed a persistent tendency to underpredict pain, and (d) higher predictions of pain, independent of pain reports, related to less range of motion during a procedure that involved painful movement. Discussion focuses on differences between these results and those of previous studies and the implications of inaccurate prediction for continued pain and disability. PMID- 8216167 TI - Are covariation biases attributable to a priori expectancy biases? AB - Illusory correlation experiments indicate that people overestimate the association between random presentations of snake slides and shock, but do not overestimate the association between random presentations of slides of damaged and exposed electric outlets (DEEOs) and shock. To investigate whether reports of covariation biases might be attributable to expectancy biases, we had Ss rate the a priori probabilities with which they would expect slides of snakes (or DEEOs), flowers, and mushrooms to be paired with shock, a tone, or nothing. In Study 1, Ss reported a pattern of a priori slide/outcome probability estimates that is nearly identical to that reported by Ss who have just undergone an illusory correlation procedure involving phylogenetic fear-relevant stimuli (e.g. snakes). Therefore, postexperimental estimates of covariation involving such stimuli appear at least partly attributable to pre-experimental expectancy biases rather than solely attributable to on-line processing biases. Study 2 revealed that Ss also display inflated a priori probability estimates for DEEO slides and shock, unlike Ss who have just undergone an illusory correlation procedure involving such stimuli. Taken together, these studies suggest that random slide/outcome pairings easily abolish pre-experimental expectancy biases for ontogenetic, but not phylogenetic, fear-relevant stimuli. PMID- 8216168 TI - Anxiety, pain and discomfort associated with dental treatment. AB - The aims of the study were to describe the level of anxiety and pain/discomfort associated with dental treatment in two samples (N = 1288 and N = 2382) representative of an adult population, and to assess the statistical effects of these variables on utilization of dental services (dental attendance measures, expenditure, and items of dental treatment received during the last year). The prevalence of high dental anxiety in the samples as measured by Corah's Dental Anxiety Scale, the Dental Fear Scale, and the Dental Anxiety Question was 4.2%, 7.1% and 5.4%, respectively. Rather large proportions of the respondents judged dental treatment to be painful or uncomfortable: between 20 and 30% rated their last dental visit as moderately painful or worse; about 60% reported having had at least one very painful experience, and 5-6% experienced dental treatment in general to be very painful. Dental anxiety was significantly related to pain reports (correlations in the 0.32-0.48 range). There were no differences between the youngest age group (15-19 yr) and the rest of the respondents in Study II with regard to dental pain ratings. Possible explanations for these findings are discussed. The effects of dental pain and anxiety on utilization measures, although attaining significance in several of the analyses, were generally weak. Both studies demonstrated few significant differences between individuals with high dental anxiety and the rest of the study samples with respect to type and extent of dental treatment received during the last year. Thus, these data seem to show that many dentally anxious patients seek out and undergo dental treatment despite high fear levels. PMID- 8216169 TI - The nature and measurement of compulsive indecisiveness. AB - Indecisiveness is an often mentioned symptom of obsessive compulsive disorder and obsessive compulsive personality disorder, yet very little research has been done examining its nature and measurement. Three studies are presented here which examine the nature of compulsive indecisiveness using a newly developed scale. In study 1 the Indecisiveness Scale was correlated with measures of obsessionality and compulsive checking among normal S s. It was also correlated with the maladaptive evaluative concern dimensions of perfectionism and with compulsive hoarding. In study 2 indecisive S s (as measured by the Indecisiveness Scale) were found to score higher on measures of procrastination and general psychopathology. In addition, they reported problems in making decisions in a variety of life domains (social, academic, family and everyday). In study 3 S s who scored high on the Indecisiveness Scale were found to have longer latencies on an experimental decision-making task. The implications of these findings for the nature of indecisiveness were discussed. PMID- 8216170 TI - A further refinement of the reliable change (RC) index by improving the pre-post difference score: introducing RCID. AB - The development of methods for demonstrating clinical (in addition to statistical) significance has been referred to as one of the major advances in outcome research. In a recent article, Speer (1992; Journal of Consulting and Clinical Psychology, 60, 402-408) suggested that the Reliable Change (RC) Index neglects possible confounding of improvement rate estimates by regression to the mean, to which latter's existence he concludes when a negative correlation between initial score and amount of change is observed. Speer (1992) proposed an alternative method that incorporates an adjustment which minimizes this confound when statistical regression has been empirically shown to be present. In the present paper, it is argued that both the rationale for arriving at this alternative method and the method itself are erroneous. Introducing RCID, the present authors provide a modification and refinement of the RC Index by improving the pre-post difference score, taking into account regression to the mean due to measurement unreliability. Further advantages of the RCID Index are briefly discussed. PMID- 8216171 TI - Mathematical performance and behavior of children with hyperactivity with and without coexisting aggression. AB - An analysis was made of a basic skill deficit and collateral behavior that could differentiate youth with hyperactivity from children with both hyperactivity and aggression. A total of 92 boys (with hyperactivity, with hyperactivity and aggression, and without disorders) were assessed for their timed performance and accuracy of computer-generated math operations. Response time differences documented between disordered and nondisordered groups, and between the diagnostic groups, were not explained by the group differences that were also observed in behavior or motor response speed (typing). Conclusions derived from these findings, and from prior work, indicated that speed of addition may be a marker of academic and social dysfunction. The overall importance of this assessment is related to the potential sensitivity of math fluency data for assessment and treatment monitoring. PMID- 8216172 TI - Effects of hydrogen peroxide on mitochondrial enzyme function studied in situ in rat heart myocytes. AB - Our previous work indicated that energy transduction, as measured by myocyte respiration, was inhibited by hydrogen peroxide, but the mitochondrial membrane potential was relatively unaffected. Therefore, we determined in the present study the critical steps in mitochondrial energy transduction by measuring the sensitivity to hydrogen peroxide of NADH-CoQ reductase, ATP synthase, and adenine nucleotide translocase in situ in myocytes. Adult rat heart cells were isolated using collagenase and incubated in the presence of 0.1-10 mM hydrogen peroxide for 30 min. Activities of NADH-CoQ reductase and oligomycin-sensitive ATP synthase were assayed enzymatically with sonicated myocytes, and adenine nucleotide translocase activities were determined by atractyloside-inhibitable [14C]ADP uptake of myocytes, permeabilized by saponin. The NADH-CoQ reductase and ATP synthase activities were inhibited to 77% and 67% of control, respectively, following an exposure to 10 mM hydrogen peroxide for 30 min. The adenine nucleotide translocase activities were inhibited in a concentration- and time dependent manner and by 10 mM hydrogen peroxide to 44% of control. The dose response relationship indicated that the translocase was the most susceptible to hydrogen peroxide among the three enzymes studied. Combined treatment of myocytes with 3-amino-1,2,4-triazole, 1,3-bis(2-chloroethyl)-1-nitrosourea and diethyl maleate (to inactivate catalase, to inhibit glutathione reductase activity, and to deplete glutathione, respectively) enhanced the sensitivity of translocase to hydrogen peroxide, supporting the view that the cellular defense mechanism is a significant factor in determining the toxicity of hydrogen peroxide. The results indicate that hydrogen peroxide can cause dysfunction in mitochondrial energy transduction, principally as the result of inhibition of adenine nucleotide translocase. PMID- 8216173 TI - Postischemic cell death in reperfused porcine hearts is not attenuated by the spin trap agent PBN during early reperfusion. AB - Ischemic, reperfused porcine hearts were used to investigate whether the spin trap agent PBN (N-tert-butyl-alpha-phenylnitrone) attenuates postischemic cell death by scavenging of free radicals. The left anterior descending coronary artery (LAD) was ligated distally in 16 pigs for 45 min and then reperfused for 3 h. PBN (coronary concentration approximately 1 mM) was infused into the LAD of eight pigs during the first 45 min of reperfusion. Electron spin resonance spectroscopy (ESR) was performed to identify free radical adducts in the reperfused coronary venous blood. Regional systolic shortening (SS%) was determined by sonomicrometry. Infarct size was evaluated as the percentage of infarcted (tetrazolium stain) to ischemic (dye technique) myocardium. The transmural ultrastructural degree of myocardial injury as well as myocardial ATP levels were assessed at the end of the experiment. Intracoronary treatment with PBN during early reperfusion did not attenuate myocardial damage. Infarct sizes (control group 59 +/- 19%, treated group 55 +/- 14%), transmural ultrastructural alterations, myocardial ATP concentrations (control group 1.8 +/- 0.3 mumol/mg frozen weight, treated group 1.7 +/- 0.4 mumol/mg) and regional systolic shortening at the end of the experiments (control group -1 +/- 5%, treated group 2 +/- 6% did not differ significantly. Furthermore, under various experimental conditions of spin trapping, free radical adducts could not be identified in coronary venous blood during early reperfusion. The results suggest that the spin trap agent PBN (1 mM) does not affect postischemic cell death in porcine hearts. PMID- 8216174 TI - Correlation of heterogeneous blood flow and fatty acid uptake in the normal dog heart. AB - Blood flow heterogeneity in normal myocardium may be caused by heterogeneous metabolic demand. We studied, from 80 tissue samples of the left ventricle (LV) of eight anesthetised, open-chest dogs (with prior beta-blockade (metoprolol) in four dogs), the radioactivity of 201Thallium-chloride (201Tl), an indicator of blood flow, and of the fatty acid 131-Iodine-heptadecanoic acid (131I-HDA), an indicator of metabolic demand, 3 min after intravenous injection. Global LV uptake (in percent of injected dose x 10(-2), per g tissue; mean +/- SD) was 4.94 +/- 0.71 for 201Tl and 4.48 +/- 0.58 for 131I-HDA in the dogs without beta blockade, and 2.08 +/- 0.26 and 1.69 +/- 0.20, respectively, in dogs with beta blockade (p < 0.05). Beta-blockade thus decreased the fraction of cardiac output delivered to the LV, concurrently with a decreased heart rate and arterial blood pressure (p < 0.05) and, thus, global metabolic demand and fatty acid uptake. Regional radioactivities per gram were normalized for mean LV radioactivities and heterogeneity was expressed as the coefficient of variation (CV). For pooled data (n = 320) in dogs without beta-blockade, regional 201Tl and 131I-HDA radioactivities varied from a factor of 0.1 to 1.6 and 0.3 to 1.8 of mean radioactivities, with a CV of 22.9 and 19.4%, respectively, and correlated (r = 0.77, p < 0.005). For pooled data (n = 320) in dogs with beta-blockade, regional 201Tl and 131I-HDA radioactivities varied from a factor of 0.2 to 1.5 and 0.2 to 1.6 of mean radioactivity and CV was 23.6% and 24.8%, respectively; r = 0.92 (p < 0.005). The endo/epi ratio for both radioactivities exceeded unity in each dog. In normal myocardium, blood flow and fatty acid uptake are thus heterogeneous, both transmurally and circumferentially, and matched, concomitantly with coupling of global blood flow to global metabolic demand and fatty acid uptake. This supports the idea that heterogeneous myocardial O2 supply reflects heterogeneous metabolic demand. PMID- 8216175 TI - Local glucose utilization and local blood flow in hearts of awake rats. AB - Local cardiac glucose utilization and local cardiac blood flow in rat heart were measured in vivo by quantitative autoradiographic techniques with 2-[14C] deoxyglucose and [14C] iodoantipyrine, respectively. [14C]methylmethacrylate standards were calibrated for quantitative autoradiography of dried sections of heart tissue; the calibration values for heart tissue differed from those for brain by 8%, probably because of differences in self-absorption within the tissues. The lumped constant required by the deoxyglucose method was determined in isolated, perfused, working rat hearts and found to be 1.11 +/- 0.36 (mean +/- SD, n = 21). The heart: blood partition coefficient for iodoantipyrine required by the [14C]iodoantipyrine method was measured and found to be 1.25. The results obtained in awake rats showed: 1) overall cardiac glucose utilization varied considerably among animals with a mean of 53 (left ventricle) and 30 (right ventricle) mumol/100 g/min; 2) cardiac blood flow was less variable among animals with a mean of 592 (left ventricle) and 420 (right ventricle) ml/100 g/min; 3) glucose utilization was found to be particularly high in the papillary muscle; 4) systematic gradients of glucose utilization or blood flow in the ventricular wall were not observed; 5) glucose utilization and blood flow were not closely correlated on a local level. It is concluded that autoradiographic methods are suitable for the quantification of local glucose utilization and local blood flow in the rat heart in vivo. These methods could not demonstrate transmural gradients for glucose utilization and blood flow between epi- and endocardium in awake rats. PMID- 8216176 TI - Infarct size in rabbits: a modified method illustrated by the effects of propranolol and trimetazidine. AB - Following a 45-min period of coronary occlusion the myocardial infarct that developed after 24 h of blood reperfusion in the rabbit heart was studied in three groups of animals: controls (n = 7), and those pretreated with 3 mg.kg-1 of the piperazine derivative, trimetazidine (n = 7) or propranolol at 0.3 mg.kg-1 (n = 6). Twenty-four hours after coronary artery ligation for 45 min infarct size was measured in myocardial slices using trinitrophenyl-tetrazolium staining, and the "area at risk" was determined by injection of zinc/cadmium particles and delineated by imaging under fluorescent light the areas of tissue that did not fluoresce. The range of "area at risk" was similar in all of the groups. There was a significant reduction in the size of infarct that developed in the trimetazidine treated group when compared with the controls. In the propranolol treated group there was a slight reduction in infarct size when compared to control, but this was less than in the trimetazidine treated group and did not reach statistical significance. It is concluded that pretreatment with trimetazidine in the blood perfused rabbit heart is effective in reducing myocardial infarct size. PMID- 8216177 TI - Time-course of left atrial performance during coronary artery occlusion followed by reperfusion in anesthetized dogs by densitometric analysis of digital atrioventriculographic images. AB - The left atrial (LA) function during coronary artery occlusion followed by reperfusion using densitometric analysis of digital atrioventriculographic images was evaluated. Eight anesthetized dogs underwent atrioventriculography at baseline, 10 and 60 min after left circumflex coronary artery (LCX) occlusion and 5, 30, 60, and 120 min of reperfusion. Time-density curves were obtained for LA and left ventricle (LV). The ratios of passive atrial video-densitometric change (VC) to total VC (Passive Ratio), and active VC to total VC (Active Ratio) were calculated. Left ventricular ejection fraction (LVEF), peak ejection rate (PER), and peak filling rate (PFR) were derived. Active Ratio, an index of atrial contraction, increased to 144%, and Passive Ratio decreased to 75% of baseline at 60 min of LCX occlusion. Two hours after reperfusion, both Active and Passive Ratios returned to control level. While LVEF reduced to 70%, PER to 67%, LV peak positive dP/dt to 88% of baseline at 60 min after occlusion, and remained depressed at 2 h after reperfusion. However, PFR, LV peak negative dP/dt and LV isovolumic pressure decay rate showed recovery at 2 h after reperfusion. There were significant correlations between PFR and Passive Ratio (r = 0.41), and between Active and Passive Ratios (r = 0.55). Thus, time-course of recovery of LV post-ischemic systolic and diastolic function was different. Return of LA function to control level during 2 h after reperfusion may be depend on recovery of LV diastolic function. PMID- 8216178 TI - Investigation of cardiac metabolism using stable isotopes and mass spectrometry. AB - The technique described in this communication enables detailed investigations of cardiac metabolism using 13C-labeled substrates and mass spectrometric measurements of 13CO2 in the coronary effluent. To validate this technique for further studies isolated working rat hearts were perfused with 13C-labeled substrates in a bicarbonate-free perfusion fluid. The fraction of CO2 produced by oxidation of labeled substrate was calculated by the 13CO2/CO2 ratio in the coronary perfusate. The oxidation of 13C-acetate showed a linear correlation with 13C-acetate concentrations between 0.015 and 0.16 mmol/l. An inhibitor of acylcarnitine translocase, 2-(3-methylcinnamylhydrazono)-propionate (BM42.304) decreased CO2 production from 13C-palmitate from 48% +/- 4% to 31% +/- 3% (n = 11, SEM). Taking into account considerations of tracer kinetic theory rapidly accessible intracellular palmitate stores were estimated to be less than 900 nmol/g ww. This technique allows specific investigations of the oxidation of labeled substrates in the heart and may be useful for basic research and/or clinical diagnosis, thus avoiding the hazards of radiolabeled substrates. PMID- 8216180 TI - The role of motor excess and instrumented activity measurement in attention deficit hyperactivity disorder. AB - Motor excess was once recognized as a primary aspect of childhood behavior disorder but has been largely discounted by current investigators despite consistent reference to hyperactivity in titles of articles, chapters, and books. The presumed minor relevance of hyperactivity to attention deficit hyperactivity disorder (ADHD) is based on analogue assessment procedures that remain to be validated. Results of content-valid instrumented behavioral measurements show that ADHD children are pervasively hyperactive. These findings are consistent with recent research showing activity to be an important aspect of temperament and a well-documented factor of externalizing disorders of childhood. Theoretical analyses of the relationship between hyperactivity and ADHD disorder are presented. PMID- 8216179 TI - Effects of arginine-vasopressin on regional blood volume distribution in supine humans. AB - In healthy humans, the increase in arterial blood pressure seen in patients with autonomic dysfunction in response to exogenous vasopressin (AVP) is abolished. We tested the hypothesis that redistribution of blood from the intra- to the extrathoracic vascular compartment might contribute to this buffer response. Regional distribution of 99mTc labeled autologous red cells was assessed in healthy supine volunteers (n = 7) during arginine-vasopressin administration (1 ng.kg-1 bolus i.v. followed by a 14-min infusion of 3 ng.kg-1 x min-1), along with arterial and central venous pressures, and heart rate. Exogenous vasopressin increased plasma vasopressin concentration from 4.0 +/- 1.4 SEM to 91 pg.ml-1 +/- 12. Thoracic counts increased slightly but significantly by 2.2% +/- 0.9, while global abdominal counts remained unchanged. Most surprisingly, counts in the liver markedly increased (+8.1% +/- 1.8, p = 0.02), but significantly decreased in the spleen (-3.1% +/- 1.4). Intestinal (-2.5% +/- 2.4) and limb counts did not change significantly. Consistent with the increase in thoracic counts central venous pressure increased from 3.6 mmHg +/- 1 to 4.7 +/- 1 (p = 0.02), while arterial pressure and heart rate did not change. All changes reversed towards baseline when vasopressin administration ceased. Thus, in humans with an intact autonomic system, vasopressin, at concentrations observed during hypotension, increases liver and, albeit to a small extent, also thoracic blood volume, but decreases splenic blood content. These results: 1) are incompatible with the hypothesis that AVP induces a shift of blood from intra- to extrathoracic capacitance vessels, and 2) show that AVP increases rather than decreases central blood volume. PMID- 8216181 TI - "What really happens in parent training?". AB - The purpose of this article was to describe the therapeutic processes involved in a parent-training program for families with conduct-disordered children. Videotaped transcriptions of over 100 hours of group discussion therapy sessions provided the data for this study. Findings indicated that the therapeutic process of helping parents learn to manage their children's behavior problems was based on a collaborative model. This model included six roles for therapists, which were labeled building a supportive relationship, empowering parents, teaching, interpreting, leading and challenging, and prophesizing. In addition, the script for parents included five recurring themes related to helping them cope more effectively. These were promoting parents' problem-solving, helping parents "come to terms" with their child, gaining empathy for their child, parents' accepting their own imperfection, and learning how to "refuel." Examples of each of these roles and themes are discussed. PMID- 8216182 TI - Training self-feeding skills in children who are deaf and blind. AB - There are very few studies that describe programs to train self-feeding skills in young children who are deaf and blind. This research reports two single-case studies on the acquisition of self-feeding in children with developmental disabilities and combined visual and auditory impairments. Study 1 included the use of prompting, prompt-fading, and contingent sensory reinforcement procedures to train independent self-feeding in a 7-year-old girl. Study 2 incorporated social reinforcement and response interruption to refine the self-feeding skills of a 6-year-old boy. Both studies were conducted by direct-care providers within an educational setting and reported maintenance of skill acquisition at 4 and 8 months posttraining. PMID- 8216183 TI - Situation specificity in attention-seeking problem behavior. A case study. AB - Previous research on attention-seeking problem behavior has focused on individuals who misbehaved under general conditions of low adult attention. In general, no detailed analyses were conducted to determine whether different situations involving low levels of adult attention (such as familiar vs. unfamiliar adults, setting events, or the presence or absence of peers) exacerbated or attenuated problem behavior. The current case study demonstrates that, for one adolescent, all situations involving low levels of adult attention were not equally discriminative for problem behavior. Two functional analyses concerning different situations involving low levels of adult attention were conducted. The first analysis consisted of systematically manipulating antecedent and consequence conditions related to adult attention and task demands. This analysis indicated that low levels of adult attention evoked problem behavior. The second analysis involved two different conditions presenting low levels of adult attention. In one, the adult spoke to another child; in the second, the adult spoke to another adult. This second analysis revealed that, when the adult spoke to another adult, problem behavior resulted. However, when the adult spoke to another child, problem behavior did not occur. On the basis of these functional analyses, a positive intervention was designed to reduce problem behavior. Theoretical implications related to functional analysis are discussed, and applied issues concerning functionally based treatment selection are explored. PMID- 8216185 TI - Antecedent manipulation in the treatment of primary solid food refusal. AB - A 4-year-old with primary solid food refusal was treated with systematic fading of utensil type and food texture, using a multiple probe design across food groups. The subject was a multi-handicapped boy hospitalized for feeding problems, self-injurious behaviors, and sleep cycle reversal. At admission, the subject received all nutrition in the form of a liquid nutritional supplement through regular bottle feedings every half hour. Craniofacial anomalies and past multiple facial surgeries precluded the use of a physical prompting procedure. During the first treatment phase, pureed foods were presented with a preexisting stimulus (a regular baby bottle). Accepted presentations were reinforced with music delivered through headphones. All other behaviors received neutral consequences. In the second treatment phase, undiluted pureed foods were presented in bottles, which allowed experimenter control of the size of the bolus entering the mouth. Consequences were identical to those in Treatment 1. Next, spoon-feedings were introduced with the same consequences in place. Reinforcement with a newly acquired preferred food was initiated and faded to a variable ratio three (VR3) schedule. This fading procedure was effective in teaching this young multihandicapped child to consume a nutritionally balanced diet of pureed foods with an average acceptance of 94% and a concomitant decrease in inappropriate mealtime behaviors. PMID- 8216184 TI - Multifactor behavioral treatment of chronic sleep-onset insomnia using stimulus control and the relaxation response. A preliminary study. AB - Sleep latency changes following behavioral interventions for sleep-onset insomnia are only moderate because the majority of insomniacs do not achieve good sleeper status at posttreatment. This study evaluated the efficacy of a multifactor behavior intervention consisting of stimulus control and relaxation-response training (n = 10) compared to stimulus control alone (n = 10) for sleep-onset insomnia. Only the multifactor subjects' mean posttest sleep latency fell within the good sleeper range. They also exhibited a 77% improvement on mean sleep-onset latency compared to the stimulus control group (63%). Thus a multifactor intervention may be more effective than stimulus control alone for treatment of sleep-onset insomnia. PMID- 8216186 TI - [Udder compatibility of tetramisole and levamisole hydrochloride and suggestion for the prescription of their intramammary use in cattle against Prototheca zopfii]. AB - Preparations with 4 percent Tetramisole or Levamisole hydrochloride were compatible in the mammary gland after application up to 40 ml/quarter (4 mg/kg body mass) for up to 6 milking times. 100 ml of the preparations were also clinically compatible in a single quarter (10 mg/kg body mass) on several days. After intramammary application of 30 ml/quarter (3 mg/kg body mass) Prototheca suppressing values in milk serum were evident for at least 6 hours. One application of 200 ml in one quarter has caused Prototheca suppressing values for 36 hours in milk serum up to dilution 1:4. Nilverm given to cattle in high dosage orally did not lead to Prototheca suppressing values in milk sera. PMID- 8216187 TI - [Experimental Prototheca mastitis in cattle and therapy with tetramisole hydrochloride]. AB - In one cow all 4 quarters were infected with 2 x 10(8) germs of Prototheca zopfii each. 2 quarters of it were treated over 6 subsequent milking times with 20 ml Tetramisole hydrochloride (4 mg/kg body mass) in each case. Clinical symptoms diminished within 3-24 hours after the first application in comparison with the control quarters distinctly. Macroscopic alterations in the treated quarters could be found for a short time only, whereas they were evident in the control quarters for up to 2 days. The milk cell counts were raised til the 5. day p.i. The number of Prototheca excreted by treated quarters in each ml initial milk was reduced to 38% and in each ml end milk to 67% in comparison with the 2 control quarters. A more potent reduction of Prototheca can be expected after the application of Levamisole hydrochloride. At the future therapy applications after every milking time for at least 3 days with 25-40 ml of the preparations in each quarter are recommended. A total dose per animal and application time of 150 ml preparations (6 g Levamisole hydrochloride = 15 mg/kg body mass) must not be exceeded. Before Levamisole hydrochloride may be used for patients, susceptibility tests are necessary of the strains of Prototheca zopfii present and additional investigations for the reliability of the results hitherto obtained in one experimental Prototheca mastitis only. PMID- 8216188 TI - [The occurrence of Prototheca in fecal samples of domestic and wild swine]. AB - Prototheca spp. were culturally detected in 64 (28.9%) fecal samples of 221 pigs and in 3 (21.4%) fecal samples of 14 wild boars by using a selective medium, developed by PORE (1973). 25 (39.1%) of 64 Prototheca positive fecal samples of pigs contained Prototheca (P.) zopfii in monoculture, while in 39 fecal samples (60.9%) a mixed culture of P. zopfii and P. moriformis was found. All 3 fecal samples of wild boards contained a monoculture of P. zopfii. The results of this study permit the conclusion that pigs as well as wild boars can harbour and shed Prototheca spp. in variable frequency. PMID- 8216189 TI - [Pilot study of the occurrence of Prototheca in fecal samples of horses]. AB - Fecal samples of 146 horses were culturally investigated for occurrence of Prototheca spp. using a selective medium, developed by PORE (1973). Prototheca zopfii could be isolated in monoculture from 9 fecal samples (6.2%). The results of this pilot study show that horses too can harbour and shed Prototheca spp. in variable frequency. PMID- 8216190 TI - [The epidemiological analysis of Salmonella typhimurium infections in cattle- results of lysotyping and biochemotyping in the region of East Thuringia from 1974 to 1991]. AB - 597 strains of Salmonella typhimurium found in samples from cattle in Eastern Thuringia from 1974 to 1991 were investigated to their phage types and biochemotypes. 21 different combined types were found out among which the phage types n.c. 1/72/n. c.(204), 2 b/23 (92) and 1 a/9 (49) dominated at certain times. With the help of two examples it is shown that cases of Salmonellosis with Salmonella typhimurium within one farm occurring one after another can be different infections that are independent from each other. The complex typings are capable to clear up epidemiological connections and therewith support the control of infections and the protection of people's health consequently. PMID- 8216191 TI - [Equine leukosis with progressive lameness--a case study]. AB - A case of generalized equine leucosis is presented. The most important clinical signs were cachexia, loss of condition, fever, tachycardia, subcutaneous tumors and severe lameness accompanied by edema of the right thoracic limb. Hematology showed anemia and neutrophilia; clinical biochemistry indicated hypalbuminemia, hyperphosphatemia and hyperfibrinogenemia. Necropsy revealed multiple tumors throughout the body which mainly originated from lymph nodes. Histopathologically the tumors consisted of two cell-types: a. uniform lymphocytoid cells with a highly infiltrative growth pattern; b. heteromorphic noninvasive lymphoblastoid cells with production of "reticular" fibers. Diagnostic problems of clinical and pathological findings are discussed. PMID- 8216192 TI - [Improvement of the rate of conception by the use of PGF2 alpha in the sow one day before weaning]. AB - The authors investigated the influence of PGF 2 alpha on rate of conception in a single large pig production unit. Two groups of sows were selected at random before weaning, forming an experimental and a control group. The groups were treated as follows: Group 1 (experimental group) received a single intramuscular dose of 3 mg Alfaprostol one day before weaning. Group 2 (control group) received a single intramuscular dose of 2 ml physiologic saline intramuscular one day before weaning. The results are evaluated on the basis of parameter "return to estrus". The experimental group showed significant less (p < 0.05) sows returning to estrus than the control. This evidence suggests that the reason of unsatisfactory breeding performance after PG F2 alpha application may be the result of other influencing factors. PMID- 8216193 TI - [The problems of quantifying pain in animals]. AB - A classification of vertebrates concerning their pain sensibility from the anatomical or physiological point of view is made very difficult by the different pathways of nociception. The very good measurable stimuli are answered by a wide range of reactions. In search for approved parameters for the characterization of pain objectivity is often preferred to validity. Studies using animals in painful situations with and without analgetic treatment are considered favourable for pain evaluation. Each kind of evaluation of pain in animals has to take into account the different dimensions of pain perception. As a result we would like to follow Kitchell's statement (1980), as a guideline for the work with animals: "Overemphasis on the uncertainty of knowledge about pain in animals that leads to a denial that pain perception exists in animals is logically as well as empirically unfounded." PMID- 8216194 TI - [Occurrence of Listeria monocytogenes in snakes, tortoises, lizards and amphibians raised as pets]. AB - Listeria (L.) spp. were isolated from fecal samples of 9 (30.0%) from 30 tortoises, of 4 (12.1%) from 33 lizards, of 3 (60.0%) from 5 amphibia and of 1 (1.3%) of 76 snakes. All animals were kept as pets. 8 isolates were identified as L. monocytogenes, whereas 4 strains were serovar 4ab (3 tortoises and 1 amphibia), 3 strains serovar 4b (2 tortoises and 1 snake) and 1 strain serovar 4e (1 amphibia). Further 4 isolates were identified as L. ivanovii serovar 5 (3 lizards and 1 tortoise), 3 strains as L. innocua serovar 6b (3 tortoises) and 2 strains as L. welshimeri serovar 6a (1 lizard) respectively serovar 6b (1 amphibia). PMID- 8216195 TI - [The use of nonpathogenic leptospira as diagnostic antigens for the diagnosis of leptospira infections in cattle]. AB - The seroprevalence of leptospira antibodies was determined in 4377 bovine sera by microagglutination assay using 11 Leptospira interrogans serovars. In 10% (439 samples) of the sera, a positive reaction was detected. These included 275 sera (62.6%) with reaction to L. grippotyphosa, 159 (36.2%) to L. saxkoebing and 5 (1.1%) sera with reactions to other serovars. Multiple reactions were found in 9.8% of the 439 positive sera, whereby the Sejroe group dominated (65%) within the possible combinations of crossreactions. To determine the suitability of nonpathogenic strains as polyvalent diagnostic antigens, two L. biflexa serovar patoc strains were compared with the above-mentioned 11 L. interrogans serovars in microagglutination testing of 1995 screen sera. The sensitivity of the test was found to be 0.3% and the specificity was 80.3%. Using the two L. patoc strains, all of the 415 positive field sera and 11 positive control sera yielded negative reactions. Based on these results, the use of L. biflexa serovar patoc cannot be recommended as polyvalent antigen in the diagnosis of bovine leptospirosis by microagglutination. PMID- 8216196 TI - [Experiences with a mobile laboratory during Operation "Kurdenhilfe" in Iran in 1991]. AB - During the operation "Kurdenhilfe" from 9th of May to 14th of June in 1991 the German army managed a field-hospital in the province Bakhtaran of Iran. Part of this field-hospital was a mobile field-laboratory in which microbiological/serological and parasitological examinations could be done. It is reported about equipment, methods and results. PMID- 8216197 TI - [Detection of antibodies against Newcastle disease virus in wild birds]. AB - 262 samples from wild birds of 26 species were examined for antibodies against the Newcastle Disease virus (NDV). By using the haemagglutination inhibition test (HI) 22 serum samples showing positive antibody titers could be detected. The epidemiology and the significance of ND for wild birds and waterfowl in farms is discussed. PMID- 8216198 TI - [The transmission of maternal Newcastle disease antibodies in pheasants]. AB - After vaccination of breeding pheasants against Newcastle disease the transmission of antibodies to chicken was investigated by serological methods (hemagglutination inhibition test). The vaccination was carried out about 4 weeks before the start of the laying season. High levels of antibodies were found in egg yolk and blood serum of three days old pheasant chicks. The antibody level dropped at the end of laying season about 10 1/2 weeks after vaccination slightly. Antibodies were found in all of the investigated eggs. PMID- 8216199 TI - [Animal welfare quo vadis: animal welfare as a constitutional goal?]. AB - From the point of view of a great research centre the introduction of animal protection in the German "Grundgesetz" raises various objections. These refer to principle law political considerations, ethical aspects and the negative influence this circumstance could have on the progress of biomedical research. PMID- 8216200 TI - [That was already known in old Rome--care of brood animals in antiquity]. AB - The paper gives an impression of the care for mother animals in antiquity, particularly in the course of Roman livestock farming (Varro, Columella). Especially noninfectious factors were held responsible for the redemption of the interruption of pregnancy and a complicated parturition. Therefore special attention was paid for the right and optimal livestock, grooming and nutrition of the farm animals. In the case of dystocia, the herdsmen and veterinarians reached for correction of presentation, traction and embryotomy during parturition. However, the placental retention was only treated with drugs. In the case of an uterine prolapse, Apsyrtos recommended for the first time the reposition at the casted animal and the triple closure of the vulva. PMID- 8216201 TI - Plant metallothioneins. PMID- 8216202 TI - Molecular modelling of the domain structure of factor I of human complement by X ray and neutron solution scattering. AB - Factor I is a typical multidomain protein of the complement system. It regulates complement activation by proteolytic degradation of C3b or C4b in the presence of factor H, complement receptor type 1, membrane cofactor protein or C4b-binding protein as cofactor. It is constructed from five presumed independently folded domains, namely a factor I module, a CD5-like domain, two low-density-lipoprotein receptor type A domains and a serine-proteinase domain. X-ray and neutron solution scattering was used to study the arrangement of these domains in factor I. Factor I was determined to be monomeric in solution, with an A280(1%,1cm) of 12.3-14.1. Its radius of gyration (RG) was 3.96 nm by X-rays in a high positive solute-solvent contrast, and 3.84 nm by neutrons at infinite solute-solvent contrast. The cross-sectional radius of gyration (RXS) was likewise found to be 1.64 nm by X-rays and 1.55 nm by neutrons. The RG data were not noticeably dependent on the solute-solvent contrast, whereas the RXS data showed a small dependence. The maximum dimension of factor I was determined to be 12.8 nm from the RG and RXS data, and 14-15 nm from the X-ray and neutron distance distribution functions. This length is too short to account for a linear arrangement of the domains in factor I. Small sphere models were developed for factor I in which the largest domain was modelled from the crystal structure for beta-trypsin. The attachment of either an elliptical cylinder or a two-armed V shaped structure to this domain to represent the remaining four small domains gave good scattering curve-fits for factor I, and were compatible with experimental sedimentation coefficients. The non-extended domain models for factor I imply that the steric accessibility of each domain will be reduced, and this may be important for its functional activity. PMID- 8216203 TI - Identity of the putative serine-proteinase fold in proteins of the complement system with nine relevant crystal structures. AB - The serine-proteinase domain is responsible for the proteolytic events that occur during complement activation. The sequences of nine serine proteinases of known crystal structure were compared with the serine-proteinase sequences in the six complement proteins C1r, C1s, C2, factor B, factor I and factor D to assess the degree of structural homology of the latter with the crystal structures. All sequence insertions and deletions were readily located at the protein surface. The internal location of disulphide bridges and the surface location of putative glycosylation sites are compatible with this structure. Secondary-structure predictions for the sequences were fully consistent with the crystal structures. It is concluded that the double subdomain beta-sheet motif is retained in the complement sequences, but that localized differences are observed for factor I, C2 and factor B. PMID- 8216204 TI - Effect of cell volume on Acridine Orange fluorescence in hepatocytes. AB - Hepatic proteolysis is inhibited by cell swelling following a variety of experimental manoeuvres, such as reduction of extracellular osmolarity, concentrative uptake of amino acids, or blockade of K+ channels by barium. On the other hand, proteolysis is known to be accomplished by pH-sensitive lysosomal proteases. Accordingly, NH3/NH4+ inhibits proteolysis by intralysosomal alkalinization. The present study has been performed to test for an effect of cell volume on the pH of acidic intracellular compartments, as assessed by Acridine Orange fluorescence at > 520 nm (F > 520). F > 520 is enhanced by NH3/NH4+ (2 and 20 mmol/l respectively), by glutamine (2 mmol/l), by the K(+) channel blocker barium (10 mmol/l) and by reduction of extracellular osmolarity (by 20 and 80 mosmol/l respectively). The observations point to release of Acridine Orange from acidic cellular compartments, which is indicative of alkalinization of these compartments during cell swelling. This effect may contribute to the regulation of proteolysis. PMID- 8216205 TI - Alpha 2(I) collagen gene expression is up-regulated in quail chondrocytes pretreated with retinoic acid. AB - alpha 2(I) collagen gene expression is induced in quail embryo chondrocytes pretreated with retinoic acid (RA). The initial appearance of alpha 2(I) mRNA occurs around day 3 of culture in RA-free medium and rapidly progresses over the next 4 days. In transient transfection assays, expression of COL1A2-CAT, a chimeric gene bearing 3500 bp upstream the bone/tendon transcription start site from the human alpha 2(I) gene fused to the CAT gene, is stimulated severalfold in RA-treated chondrocytes. In contrast, enzyme activity is very low in untreated chondrocytes, suggesting that the sequences required for RA-induced transcription of the alpha 2(I) gene are present in this plasmid. Analysis of alpha 2(I) promoter sequences performed with deletion mutants gives overlapping results in collagen type I-producing fibroblasts and chondrocytes withdrawn from RA treatment. These experiments suggest that RA-induced transcription of the alpha 2(I) collagen gene in chondrocytes is regulated by the binding of transcription factors to the same regulatory sequences that control transcription in fibroblasts. PMID- 8216206 TI - Free ADP-ribose in human erythrocytes: pathways of intra-erythrocytic conversion and non-enzymic binding to membrane proteins. AB - We have previously identified free ADP-ribose (ADPR) as a normal metabolite in mature human erythrocytes. In this study the metabolic transformations of ADPR were investigated in both supernatants from erythrocyte lysates and intact erythrocytes, loaded with ADPR by means of a procedure involving hypotonic haemolysis and isotonic resealing. In both experimental systems, the main pathway was a dinucleotide pyrophosphatase-catalysed hydrolysis to yield AMP, which was readily converted into the adenylic and inosinic nucleotide pools. To a lesser extent, ADPR underwent conversion into a compound that was identified as ADP ribulose (ADPRu), on the basis of m.s., n.m.r. spectroscopy and enzymic analysis. ADPRu was also susceptible to degradation by the dinucleotide pyrophosphatase, which was partially purified from erythrocyte lysates and characterized with respect to its substrate specificity. Isomerization of ADPR to ADPRu was markedly enhanced by ATP. Incubation of unsealed haemoglobin-free erythrocyte membranes with labelled ADPR did not cause any transformation of this nucleotide and resulted in its trichloroacetic acid- and formic acid-resistant binding to a number of membrane cytoskeletal proteins. These proteins include spectrin, glyceraldehyde 3-phosphate dehydrogenase (Ga3PDH), three proteins of molecular masses 98, 79 and 72 kDa, which apparently comigrate with bands 3, 4.1 and 4.2 respectively, and two additional proteins of molecular masses 58 and 41 kDa. Acid resistant binding of ADPR, as well as of NAD+, to Ga3PDH was confirmed for the enzyme purified from human erythrocytes. PMID- 8216208 TI - Degradation of surfactant-associated protein B (SP-B) during in vitro conversion of large to small surfactant aggregates. AB - Pulmonary surfactant obtained from lung lavages can be separated by differential centrifugation into two distinct subfractions known as large surfactant aggregates and small surfactant aggregates. The large-aggregate fraction is the precursor of the small-aggregate fraction. The ratio of the small non-surface active to large surface-active surfactant aggregates increases after birth and in several types of lung injury. We have utilized an in vitro system, surface area cycling, to study the conversion of large into small aggregates. Small aggregates generated by surface area cycling were separated from large aggregates by centrifugation at 40,000 g for 15 min rather than by the normal sucrose gradient centrifugation. This new separation method was validated by morphological studies. Surface-tension-reducing activity of total surfactant extracts, as measured with a pulsating-bubble surfactometer, was impaired after surface area cycling. This impairment was related to the generation of small aggregates. Immunoblot analysis of large and small aggregates separated by sucrose gradient centrifugation revealed the presence of detectable amounts of surfactant associated protein B (SP-B) in large aggregates but not in small aggregates. SP-A was detectable in both large and small aggregates. PAGE of cycled and non-cycled surfactant showed a reduction in SP-B after surface area cycling. We conclude that SP-B is degraded during the formation of small aggregates in vitro and that a change in surface area appears to be necessary for exposing SP-B to protease activity. PMID- 8216207 TI - Identification of the predominant glycosaminoglycan-attachment site in soluble recombinant human thrombomodulin: potential regulation of functionality by glycosyltransferase competition for serine474. AB - Thrombomodulin (TM) is an endothelial cell thrombin receptor that converts thrombin from a procoagulant to an anticoagulant enzyme. It has previously been shown that TM is expressed in both a high-M(r) form containing chondroitin sulphate and a low-M(r) form lacking this modification. Site-directed mutagenesis of a soluble human TM derivative (TMD1) was employed to determine the attachment site(s) of this functionally important oligosaccharide on the core protein. Although there are four serine residues within the Ser/Thr-rich domain of TMD1 that might support glycosaminoglycan assembly, our analysis demonstrates that the primary site of attachment is at Ser474, and evidence is presented for low levels of attachment at Ser472. It was possible to improve the overall degree of attachment by mutating Ser472 to glutamic acid (so as to conform Ser474 to the xylosyltransferase acceptor consensus acidic-Gly-Ser-Gly-acidic); however, a significant proportion (approx. 35%) of the total TM still lacked a glycosaminoglycan moiety. Mutants that possess a substitution for Ser474 show an increased mobility of their low-M(r) form on SDS/PAGE compared with native TMD1. Isolation and sequencing of a C-terminal peptide demonstrated that this serine is modified in the low-M(r) form of native TMD1. An apparent 'acceptor consensus overlap' at Ser474 suggests that the mechanism behind the glycosaminoglycan split of TM may involve a competition for substrate between xylosyltransferase and N acetylgalactosaminyltransferase. PMID- 8216209 TI - Purification and properties of the enzyme arylamine N-acetyltransferase from the housefly Musca domestica. AB - The enzyme arylamine N-acetyltransferase (ANAT) from the housefly (Musca domestica) has been purified. The M(r) of the purified enzyme was 27,600 +/- 1700 as estimated by gel filtration. SDS/PAGE yielded a value of 26,000 +/- 300, clearly indicating a monomeric structure. The purified enzyme had apparent Km values for acetyl-CoA and tyramine of 8.4 microM and 8.8 microM respectively, a pH optimum of 7.2 in 10 mM potassium phosphate buffer and an apparent pI of 5.8. ANAT activity showed a strong dependency on the presence of 2-mercaptoethanol during the purification stages. The enzyme could be completely inactivated by treatment with p-chloromercuribenzoate although the enzyme activity was protected by preincubation with acetyl-CoA. One or more cysteine residues are clearly required for catalytic activity, as demonstrated for the mammalian enzyme. In contrast, partial sequencing of the enzyme has yielded a number of peptide sequences, including the N-terminal sequence, which show no similarity with those reported for the mammalian and avian enzymes. PMID- 8216210 TI - Decrease in cerebral inositols in rats and humans. AB - Rats with portacaval shunts and humans with hepatic encephalopathy show severe myo-inositol depletion in the brain. The portacaval-shunted rat may therefore be a useful model for the investigation of neurochemical pathways containing myoinositol, which are modulated not only in hepatic encephalopathy but also in diabetes mellitus and Alzheimer's disease. PMID- 8216211 TI - Effects of insulin and phorbol esters on MARCKS (myristoylated alanine-rich C kinase substrate) phosphorylation (and other parameters of protein kinase C activation) in rat adipocytes, rat soleus muscle and BC3H-1 myocytes. AB - To evaluate the question of whether or not insulin activates protein kinase C (PKC), we compared the effects of insulin and phorbol esters on the phosphorylation of the PKC substrate, i.e. myristoylated alanine-rich C-kinase substrate (MARCKS). In rat adipocytes, rat soleus muscle and BC3H-1 myocytes, maximally effective concentrations of insulin and phorbol esters provoked comparable, rapid, 2-fold (on average), non-additive increases in the phosphorylation of immunoprecipitable MARCKS. These effects of insulin and phorbol esters on MARCKS phosphorylation in intact adipocytes and soleus muscles were paralleled by similar increases in the phosphorylation of an exogenous, soluble, 85 kDa PKC substrate (apparently a MARCKS protein) during incubation of post-nuclear membrane fractions in vitro. Increases in the phosphorylation of this 85 kDa PKC substrate in vitro were also observed in assays of both plasma membranes and microsomes obtained from rat adipocytes that had been treated with insulin or phorbol esters. These insulin-induced increases in PKC-dependent phosphorylating activities of adipocyte plasma membrane and microsomes were associated with increases in membrane contents of diacylglycerol, PKC-beta 1 and PKC-beta 2. Our findings suggest that insulin both translocates and activates PKC in rat adipocytes, rat soleus muscles and BC3H-1 myocytes. PMID- 8216212 TI - Continuous bioluminescent monitoring of cytoplasmic ATP in single isolated rat hepatocytes during metabolic poisoning. AB - We have devised a technique for monitoring cytoplasmic ATP continuously in single hepatocytes. Single isolated rat hepatocytes were injected with the ATP-dependent luminescent protein firefly luciferase, and then superfused with 45 microM luciferin in air-equilibrated medium. Signals of approx. 10-200 photoelectron counts per second could be recorded from individual healthy cells for up to 3 h. The response of the luminescent signal to chemical hypoxia (2-5 mM CN- and 5-10 mM 2-deoxyglucose) was monitored. We found a great cell-to-cell variability in the time course of the ATP decline in response to CN-, 2-deoxyglucose or to their combination; the time for the signal to fall to 10% of the original (corresponding to approx. 100 microM ATP) ranged from approx. 20 to 75 min. This resistance of the cytoplasmic ATP concentration to depletion after blockade of oxidative phosphorylation and glycolysis could be abolished by pretreatment of the cells with etomoxir, which blocks mitochondrial beta-oxidation. Etomoxir alone had no effect on the luciferase signal, but etomoxir-pre-treated cells showed a prompt fall in the luciferase signal starting within 1-2 min of application of cyanide and 2-deoxyglucose and falling to 10% of the original signal in approx. 6-10 min. The technique allows cytoplasmic ATP changes to be monitored in single hepatocytes at concentrations of 1 mM or lower, but more precise calibration of the signal will require correction for the effects of cytoplasmic pH changes. PMID- 8216213 TI - Physiological modulation of the uptake and fate of glucose in brown adipose tissue. AB - Glucose utilization indices (GUI values) and rates of fatty acid synthesis in interscapular brown adipose tissue (IBAT) varied during the diurnal cycle in virgin and late-pregnant rats permitted unrestricted access to food. In virgin rats, peak GUI values and lipogenic rates were observed at the end of the dark (feeding) phase, but were not sustained during the light phase. Whereas peak GUI values were comparable with those observed during re-feeding after 24 h starvation, maximum rates of IBAT fatty acid synthesis in virgin rats during the diurnal cycle were only approx. 25% of those measured during re-feeding after 24 h starvation. Despite hyperphagia, GUI values during the diurnal cycle in late pregnant rats fed ad libitum were generally lower than those of age-matched virgin controls. The percentage of pyruvate dehydrogenase complex present in the active form (PDHa) was also significantly decreased. Suppression of GUI and PDHa was not parallelled by suppression of fatty acid synthesis. IBAT GUI values in late-pregnant rats during chow re-feeding ad libitum after 24 h starvation were only 25% of those of corresponding virgin controls, and stimulation of fatty acid synthesis was also dramatically attenuated. The suppression of IBAT GUI values after re-feeding in pregnancy was not due to depletion of GLUT 4 protein. The results are discussed in relation to the importance of glucose as a precursor for fatty acid synthesis in IBAT. PMID- 8216214 TI - Ligand-induced conformational changes modify proteolytic cleavage of the adipocyte insulin-sensitive glucose transporter. AB - The transport conformation of the human erythrocyte glucose transporter (GLUT1) modifies rates of proteolytic cleavage of this protein by a variety of enzymes. We investigated the effects of ligand-induced conformational change on the susceptibility to enzymic cleavage of the insulin-sensitive rat adipocyte glucose transporter (GLUT4). A GLUT4-enriched slow sedimenting microsomal fraction was prepared from basal adipocytes and subjected to PAGE and immunoblotting. The GLUT4 protein was detected in these immunoblots with a C-terminal-specific antiserum as an M(r)-46,000-50,000 doublet. GLUT1 protein was not detected by a GLUT1-specific antiserum in these membranes. Tryptic digestion caused loss of the GLUT4 signal in immunoblots in a time- and concentration-dependent fashion. Low M(r) membrane-bound fragments were not observed in electrophoretic gels, whether detection was attempted by immunoblotting or by counting radioactivity in gel slices following photolabelling with [3H]cytochalasin B. Transport-specific ligands known to induce an outward-facing conformation in the human erythrocyte GLUT1 protein retarded cleavage of the GLUT4 protein by submaximal concentrations of trypsin, whereas ligands known to induce an inward-facing conformation increased the extent of cleavage. The transported substrate D-glucose retarded tryptic cleavage of GLUT4. This result contrasts with the known behaviour of GLUT1, in which D-glucose accelerates cleavage. Cleavage of GLUT4 by thermolysin was also retarded by the outward-binding analogue 4,6-O-ethylidene glucose. These results show that the conformational sensitivity to proteolysis of GLUT4 mirrors that of GLUT1, except that the glucose-loaded GLUT4 has a different steady-state configuration, which may reflect underlying kinetic differences between the two proteins. PMID- 8216215 TI - Reduction of the surface-tension-lowering ability of surfactant after exposure to hypochlorous acid. AB - The reactive species hypochlorous acid (HOCl/OCl-) is a major product of the respiratory burst in activated neutrophils. We studied the effects of HOCl/OCl- on human surfactant and upon surfactants Survanta, KL4 and Exosurf, utilizing a pulsating surfactometer for measuring surface tension. HOCl/OCl- induced a marked dose-dependent decrease in the surface-tension-lowering activity of human surfactant. The surfactant containing surfactant proteins B and C (Survanta) was less sensitive; however, synthetic surfactants with or without peptides were not affected by HOCl/OCl- (KL4, Exosurf). Ascorbic acid and GSH protected human surfactant against inactivation by HOCl/OC1-. We suggest that HOCl/OCl- produced by activated phagocytes in the alveolar compartment of the lung could damage endogenous surfactant and affect the function of exogenously administered natural or other surfactants, especially if ascorbic acid and GSH levels in the lung lining fluids are subnormal, as is known to be the case in some inflammatory lung diseases. PMID- 8216216 TI - A novel mono-branched lipid phosphate acts as a substrate for dolichyl phosphate mannose synthetase. AB - Dolichyl phosphate mannose synthetase (GDP-mannose: dolichyl-phosphate O-beta-D mannosyltransferase; EC 2.4.1.83) is an enzyme that is involved in glycoconjugate biosynthesis and possesses a putatively conserved dolichol binding site. In order to probe the interaction between the enzyme and the dolichol chain, lipid phosphates varying in length and extent of branching have been tested as substrates in crude microsomal preparations from Saccharomyces cerevisiae. It was found that phytanyl (3,7,11,15-tetramethylhexadecanyl) phosphate was utilized at 60-70% of the efficiency of the natural dolichyl lipid in transfer of [3,4, 3H]mannose from GDP-Man to organic soluble material, whereas addition of S-3 methyloctadecanyl phosphate, which is of similar length to the phytanyl analogue but with only one branch, resulted in approximately 25% of the incorporation of the natural substrate. Incubations with the unbranched tetradecanyl phosphate and with the short, doubly branched R- and S-dihydrocitronellyl (3,7-dimethyloctanyl) phosphates exhibited levels of activity similar to incubations with no exogenous acceptor. These results were qualitatively confirmed with experiments on Escherichia coli harbouring the S. cerevisiae DPM1 gene. The [3H]mannosylated lipid-linked material from microsomal incubations was purified by anion-exchange chromatography. The major saccharide component recovered after hydrolysis was determined to be mannose, but a mannose-containing disaccharide was also present. It is concluded that branching of lipid phosphates is essential for substrates of dolichyl phosphate mannose synthetase and that significant transfer of mannose occurs even if only branching at C-3 is present. PMID- 8216217 TI - S-adenosyl-L-methionine decarboxylase of Acanthamoeba castellanii (Neff): purification and properties. AB - S-Adenosyl-L-methionine decarboxylase (AdoMetDC) has been purified to near homogeneity from the Neff strain of Acanthamoeba castellanii. The holoenzyme molecular mass is 88.8 kDa, including two copies each of a 32.8 kDa alpha-subunit and a 10-15 kDa beta-subunit. The alpha-subunit contains the active site. It has an N-terminal pyruvoyl group, and the first 19 amino acids are 63 and 74% identical with comparable sequences from yeast and mammals, respectively. The apparent Km for S-adenosylmethionine (AdoMet) in the presence of 2 mM putrescine was 30.0 microM. The enzyme was stimulated 2-fold by putrescine, but was unaffected by spermidine. It was inhibited by the following anti-metabolites, listed with their Ki values: Berenil (0.17 microM), pentamidine (19.4 microM), propamidine (334 microM), hydroxystilbamidine (357 microM), methylglyoxal bis(guanylhydrazone) (604 microM) and ethidium bromide (1.3 mM). Activity of the enzyme fell to undetectable levels during cell differentiation (encystment). PMID- 8216218 TI - Differential responses of intestinal glucose transporter mRNA transcripts to levels of dietary sugars. AB - Dietary sugars are known to stimulate intestinal glucose transport activity, but the specific signals involved are unknown. The Na(+)-dependent glucose co transporter (SGLT1), the liver-type facilitative glucose transporter (GLUT2) and the intestinal-type facilitative glucose transporter (GLUT5) are all expressed in rat jejunum [Miyamoto, Hase, Taketani, Minami, Oka, Nakabou and Hagihira (1991) Biochem. Biophys. Res. Commun. 181, 1110-1117]. In the present study we have investigated the effects of dietary sugars on these glucose transporter genes. A high-glucose diet stimulated glucose transport activity and increased the levels of SGLT1 and GLUT2 mRNAs in rat jejunum. 3-O-Methylglucose, D-galactose, D fructose, D-mannose and D-xylose can mimic the regulatory effect of glucose on the SGLT1 mRNA level in rat jejunum. However, only D-galactose and D-fructose increased the levels of GLUT2 mRNA. The GLUT5 mRNA level was increased significantly only by D-fructose. Our results suggest that the increase in intestinal transport activity in rats caused by dietary glucose is due to an increase in the levels of SGLT1 and GLUT2 mRNAs, and that these increases in mRNA may be caused by an enhancement of the transcriptional rate. Furthermore, for expression of the SGLT1 gene, the signal need not be a metabolizable or transportable substrate whereas, for expression of the GLUT2 gene, metabolism of the substrate in the liver may be necessary for signalling. Only D-fructose is an effective signal for expression of the GLUT5 gene. PMID- 8216219 TI - Induction of peroxisomal beta-oxidation by a microbial catabolite of cholic acid in rat liver and cultured rat hepatocytes. AB - The capability of (4R)-4-(2,3,4,6,6a beta,7,8,9,9a alpha,9b beta-decahydro-6a beta-methyl-3-oxo-1H-cyclopental[f]quinolin-7 beta-yl)valeric acid (DCQVA), a catabolite of cholic acid produced by enterobacteria, to induce peroxisome proliferation in vivo and in vitro was studied. Rats given 0.3% DCQVA in the diet for 2 weeks showed marked increases in peroxisomal beta-oxidation, mitochondrial 2,4-dienoyl-CoA reductase and microsomal laurate omega-oxidation activities in the liver compared with control rats given the diet without DCQVA. Cultured rat hepatocytes treated with DCQVA for 72 h also exhibited greatly enhanced beta oxidation activity. The increased activity was concentration-dependent and the effective concentrations were comparable with those of clofibric acid that produced the same degree of induction in the assay. The results demonstrate that DCQVA is a potent peroxisome proliferator that occurs naturally in rat intestine. PMID- 8216220 TI - Translocation of alpha-sarcin across the lipid bilayer of asolectin vesicles. AB - alpha-Sarcin is a cytotoxic protein produced by the mould Aspergillus giganteus. Insertion of alpha-sarcin into asolectin membranes has been demonstrated by protein labelling with photoreactive phospholipids. alpha-Sarcin added externally to tRNA-containing asolectin liposomes degrades the entrapped tRNA. Trypsin containing asolectin liposomes were also prepared. Encapsulated trypsin degrades alpha-sarcin, even in the presence of a large excess of external hen egg-white trypsin inhibitor to prevent any alpha-sarin degradation outside the vesicles. These processes occur only with acidic phospholipids and were not observed when phosphatidylcholine vesicles were used. These results indicate that alpha-sarcin penetrates the lipid bilayer and becomes exposed to the lumen of negatively charged liposomes. PMID- 8216221 TI - Identification of hepatocyte nuclear factor-3 binding sites in the Clara cell secretory protein gene. AB - To determine the mechanisms of cell-specific gene expression in the developing pulmonary epithelium the Clara cell secretory protein (CCSP) gene promoter was analysed by DNAase I footprinting. A prominent site of protein-DNA interaction was detected from nucleotides -132 to -76 using nuclear extract from mouse lung and human H441 cells. Mobility shift analysis revealed that an oligonucleotide corresponding to this region interacted with multiple proteins from lung and H441 cell nuclear extracts. Analysis of the nucleotide sequence of this region identified two potential binding sites for hepatocyte nuclear factor 3 (HNF-3), and consistent with this finding binding to this CCSP oligonucleotide was specifically competed for by an oligonucleotide corresponding to the HNF-3 binding site from the mouse transthyretin gene. Mobility shift of the CCSP oligonucleotide was supershifted using antisera specific to HNF-3 alpha and HNF-3 beta, and HNF-3 alpha and HNF-3 beta translated in vitro were found to bind specifically to this same oligonucleotide. Co-transfection of HNF-3 alpha- and HNF-3 beta-expression plasmids increased cell-specific reporter gene activity in H441 cells transfected with a CCSP-CAT gene chimeric construct containing this 132 to -76 region. Taken together, these results suggest a role for HNF-3 in mediating cell-specific CCSP gene expression within the bronchiolar epithelium. These findings support the hypothesis that members of the HNF-3 'forkhead' family of transcription factors determine gene expression and cell fate in multiple cell lineages derived from the primitive gut endoderm. PMID- 8216222 TI - Biosynthesis, structure and biological activity of hydroxyeicosatetraenoic acids in Hydra vulgaris. AB - Recent reports have suggested the involvement of arachidonic acid (AA) and its metabolites in the control of body pattern, head and tentacle regeneration and bud formation in Hydra spp. Here we describe for the first time the biosynthesis of hydroxyeicosatetraenoic acids (HETEs) in vitro by hydroid cytosolic extracts. Incubation of both unlabelled and tritiated AA with homogenates of Hydra vulgaris led to the conversion of up to 11% of the exogenous fatty acid into mainly two metabolites. These were characterized as 11-hydroperoxyeicosatetraenoic acid (11 HPETE) and 11-HETE by means of a combination of chromatographic, chemical, 1H n.m.r. and electron-impact m.s. techniques. Trace amounts of 9-HETE and 12-HETE were also found. Analysis of 11-HETE by chiral-phase h.p.l.c. revealed that this metabolite was composed mainly of the R enantiomer. The production of 11-HPETE and 11-HETE was found to be: (1) associated with the cytosolic fraction of Hydra homogenates; (2) dependent on AA concentration, incubation time and protein amount in the homogenates; (3) unaffected by co-incubation with the 5- and 12 lipoxygenase inhibitors, 5,8,11-eicosatriynoic acid and nordihydroguaiaretic acid, the cyclo-oxygenase inhibitor, indomethacin, or the cytochrome P-450 inhibitors, proadifen and methoxalen. These results strongly suggest the presence of a very active (R)-11-lipoxygenase in H. vulgaris. The activity of both R and S enantiomers of synthetic 9-, 11- and 12-HETE and of 'endogenous' 11-HETE was studied on tentacle regeneration and bud formation in decapitated Hydra. Although almost all compounds tested inhibited budding, only endogenous 11-HETE and synthetic (R)-11-HETE significantly enhanced the average number of tentacles, thus suggesting that this eicosanoid might be one of the cellular regulators of regeneration in H. vulgaris. PMID- 8216223 TI - The helix-loop-helix transcription factor USF (upstream stimulating factor) binds to a regulatory sequence of the human insulin gene enhancer. AB - Two important sequence elements, designated insulin enhancer binding site 1 (IEB1) or NIR and IEB2 or FAR, are involved in regulating expression of the rat insulin I gene. These elements bind a helix-loop-helix transcription factor, insulin enhancer factor 1 (IEF1). The IEB1 site is highly conserved among insulin genes but the IEB2 site is not conserved. To investigate the factors binding at the equivalent IEB1 and IEB2 sites in the human insulin gene enhancer, electrophoretic mobility shift assays were performed using a variety of cell extracts and probes specific for the homologous IEB1 and IEB2 sites. The results indicate that a factor with similar tissue distribution and binding characteristics to those of IEF1 binds to the IEB1 site in the human insulin gene, but that a separate factor, identified as the adenovirus major late transcription factor [MLTF, or upstream stimulating factor (USF)] binds to the IEB2 site. PMID- 8216224 TI - Interaction of activated protein C with serpins. AB - The inhibition of activated protein C by six different serine protease inhibitors (serpins) that have arginine residues in the P1 position has been investigated. Micromolar concentrations of C1-inhibitor failed to inhibit the enzyme, and it was inhibited only slowly by antithrombin III with an association rate constant (kass.) of 0.15 M-1.s-1. The kass. values for the other serpins tested (protease nexin I, protein C inhibitor, and mutants of alpha 1-antichymotrypsin and alpha 1 antitrypsin with P1 arginine residues) were at least 1000-fold higher, with P1 Arg-alpha 1-antitrypsin (kass. = 7 x 10(4) M-1.s-1) being the most effective inhibitor. The inhibition with these four serpins appeared to be reversible, with inhibition constants in the nanomolar range. The relatively high value of kass. for protease nexin I (5 x 10(3) M-1.s-1) suggested that it may be involved in the control of activated protein C on the surface of platelets where protein nexin I is present at relatively high concentrations. The value of kass. for protease nexin I, protein C inhibitor and antithrombin III showed a bell-shaped dependence on heparin concentration. At optimal concentrations, heparin accelerated the rate of inhibition by protease nexin I, protein C inhibitor and antithrombin III by 44 , 18- and 13-fold respectively. The kinetic constants for the inhibition of thrombin were also determined, and in all cases the serpins were more effective inhibitors of thrombin. Comparison of the sequences of the active-site regions of activated protein C and thrombin suggested that the more hydrophobic active site of thrombin may be more favourable for interactions with serpins. PMID- 8216225 TI - Degradation of rat C-reactive protein by macrophages. AB - Rat C-reactive protein (CRP) is a serum glycoprotein belonging to the 'pentraxin' family of proteins. In this study we have shown the specific binding of 125I-CRP to rat peritoneal macrophages at 4 degrees C. This binding was dependent upon incubation time, CRP and cell concentrations, and was not inhibited by either phosphorylcholine or human IgG. At 37 degrees C, the surface-bound 125I-CRP was internalized and degraded. The degradation of 125I-CRP was measured by the formation of 125I-labelled trichloroacetic-acid-soluble CRP peptides by either precipitation assays or by h.p.l.c. of the incubation medium using a gel filtration column. Since chloroquine and leupeptin inhibited CRP degradation, it was concluded that degradation of CRP occurred in the lysosomal compartment of the macrophage. There was an absolute requirement for the presence of bivalent cations (Ca2+ and Mg2+) in the incubation medium for the binding and degradation of CRP, which could be inhibited by EDTA but not by phosphorylcholine or human IgG. H.p.l.c. analysis of the medium obtained from incubation of macrophages with 125I-CRP revealed the presence of 125I-labelled low-M(r) peptides, the formation of which was dependent upon incubation time. PMID- 8216226 TI - Modulation of extracellular ATP-induced Ca2+ responses: role of protein kinases. AB - Evidence for the modulation of the P2z-purinoceptor for extracellular ATP in dissociated rat parotid cells is presented in studies using compounds that inhibit protein kinases. Preincubation of acinar cells with the protein kinase catalytic-site inhibitors K-252a and staurosporine, as well as with the regulatory-domain inhibitor sphingosine, specifically potentiates the elevation in cytosolic Ca2+ concentration ([Ca2+]i) mediated by extracellular ATP, but has no effect on the [Ca2+]i elevation mediated by muscarinic receptors through phospholipase C activation. Phorbol dibutyrate (PDBu), which activates protein kinase C (PKC), has no modulatory effect on ATP-mediated [Ca2+]i elevation. Further, pretreatment with PDBu does not reverse or block the effects of K-252a or sphinogosine, arguing against the involvement of PKC. Other pharmacological manipulations indicate that neither calmodulin-dependent nor cyclic-AMP-dependent kinases are involved. Neither the peak intracellular Ca2+ mobilization nor the sustained Ca2+ entry in response to carbachol or to a Ca2+ ionophore (4-bromo A23187) is altered by the kinase inhibitors that potentiate the [Ca2+]i response to ATP, indicating that effects on the ATP response are not due to non-specific permeability changes, nor to decreased Ca2+ removal from the cytosol. ATP mediated influx of Mn2+ as well as ATP-induced membrane depolarization are potentiated in cells preincubated with K-252a, directly demonstrating that cation influx is enhanced through a P2z-specific route. These results show that P2z responses (or purinoceptors) can be modulated and suggest that phosphorylation events are involved. PMID- 8216227 TI - Alterations in the expression of G-proteins and regulation of adenylate cyclase in human neuroblastoma SH-SY5Y cells chronically exposed to low-efficacy mu opioids. AB - Western-blot analysis of human neuroblastoma SH-SY5Y cells (mu- and delta receptors) revealed the presence of the following G-protein subunits: Gi alpha 1, Gi alpha 2, Gs alpha, G(o) alpha, Gz alpha, and G beta, a pattern resembling that observed in central nervous tissue. Chronic treatment of differentiated [all trans-retinoic acid (10 microM; 6 days)] SH-SY5Y cells with D(-)-morphine (10 microM; 3 days) significantly increased the abundance of all G-protein subunits identified. Co-incubation of morphine-exposed cells together with naloxone (10 microM; 3 days) or the mu-selective opioid antagonist CTOP (10 microM; 3 days), but not with the delta-selective antagonist ICI-174,864 (10 microM; 3 days), completely abolished this effect, suggesting that the increase in G-protein abundance is specifically mediated by mu-receptors. Moreover, the biologically inactive enantiomer L(+)-morphine (10 microM; 3 days) failed to produce a similar effect. G-protein up-regulation developed in a time- and dose-dependent manner and is most likely due to enhanced protein synthesis de novo, since concomitant treatment of the cells with cycloheximide (100 micrograms/ml; 3 days) prevented this effect. Chronic treatment with the low-efficacy mu-selective opioid peptide morphiceptin (10 microM; 3 days), but not with the highly potent mu-agonist DAGO (0.1 microM; 3 days) produced a comparable increase in G-protein abundance. Coincident with quantitative effects on G-protein levels in morphine tolerant/dependent SH-SY5Y cells, we found elevated levels of basal, forskolin (1 microM)- and prostaglandin-E1 (1 microM)-stimulated adenylate cyclase activities. Reconstitution experiments using S49 cyc- lymphoma-cell membranes suggest that this increase is most likely due to elevated levels of functionally intact Gs. Chronic treatment with both morphine and DAGO induces high degrees of tolerance in this cell line. However, the intrinsic activity of G1 was unchanged, as assessed in functional studies with low-nanomolar concentrations of guanosine 5' [beta gamma- imido]triphosphate. Our data demonstrate that chronic treatment of SH-SY5Y cells with low-efficacy mu-opioids increases G-protein abundance, a phenomenon which might contribute to the biochemical mechanisms underlying opioid tolerance/dependence. PMID- 8216228 TI - Fibroblast and neutrophil collagenases cleave at two sites in the cartilage aggrecan interglobular domain. AB - The actions of recombinant human fibroblast collagenase (MMP1), purified polymorphonuclear leucocyte collagenase (MMP8) and their N-terminal catalytic domain fragments against cartilage aggrecan and an aggrecan G1-G2 fragment have been investigated in vitro. After activation with recombinant human stromelysin and typsin, both collagenases were able to degrade human and porcine aggrecans to a similar extent. An N-terminal G1-G2 fragment (150 kDa) was used to identify specific cleavage sites occurring within the proteinase-sensitive interglobular domain between G1 and G2. Two specific sites were found; one at an Asn341-Phe342 bond and another at Asp441-Leu442 (human sequence). This specificity of the collagenases for aggrecan G1-G2 was identical with that of the truncated metalloproteinase matrilysin (MMP7), but different from those of stromelysin (MMP3) and the gelatinases (MMP2 or gelatinase A; MMP9 or gelatinase B) which cleave at the Asn-Phe site, but not the Asp-Leu site. In addition, collagenase catalytic fragments lacking C-terminal hemopexin-like domains were tested and shown to exhibit the same specificities for the G1-G2 fragment as the full-length enzymes. Thus the specificity of the collagenases for cartilage aggrecan was not influenced by the presence or absence of the C-terminal domain. Together with our previous findings, the results show that stromelysin-1, matrilysin, gelatinases A and B and fibroblast and neutrophil collagenases cleave at a common, preferred site in the aggrecan interglobular domain, and additionally that both fibroblast and neutrophil collagenases cleave at a second site in the interglobular domain that is not available to stromelysin or gelatinases. PMID- 8216229 TI - Characterization of the type I dehydroquinase from Salmonella typhi. AB - The type I dehydroquinase from the human pathogen Salmonella typhi was overexpressed in an Escherichia coli host and purified to homogeneity. The S. typhi enzyme was characterized in terms of its kinetic parameters, important active-site residues, thermal stability and c.d. and fluorescence properties. In all important respects, the enzyme from S. typhi behaves in a very similar fashion to the well-characterized enzyme from E. coli, including the remarkable conformational stabilization observed on reduction of the substrate/product mixture by NaBH4. This gives confidence that the information from X-ray studies on the S. typhi enzyme [Boys, Fawcett, Sawyer, Moore, Charles, Hawkins, Deka, Kleanthous and Coggins (1992) J. Mol. Biol. 227, 352-355] can be applied to other type I dehydroquinases. Studies of the quenching of fluorescence of the S. typhi enzyme by succinimide show that NaBH4 reduction of the substrate/product imine complex involves a dramatic decrease in the flexibility of the enzyme, with only very minor changes in the overall secondary and tertiary structure. PMID- 8216230 TI - Glucose transporters and in vivo glucose uptake in skeletal and cardiac muscle: fasting, insulin stimulation and immunoisolation studies of GLUT1 and GLUT4. AB - Our aim was to study glucose transporters GLUT1 and GLUT4 in relation to in vivo glucose uptake in rat cardiac and skeletal muscle. The levels of both transporters were of a similar order of magnitude in whole muscle tissue (GLUT1/GLUT4 ratio varied from 0.1 to 0.6), suggesting that both may have an important physiological role in regulating muscle glucose metabolism. GLUT4 correlated very strongly (r2 = 0.97) with maximal insulin-stimulated glucose uptake (Rg' max., estimated using the glucose clamp plus 2-deoxy[3H]glucose bolus technique) in six skeletal muscles and heart. A distinct difference in regulation of the two transporters was evident in heart: in 5 h-fasted rats, basal glucose uptake and GLUT1 levels in heart were very high and both were reduced, by 90 and 60% respectively, by 48 h fasting. However, in heart (and in red skeletal muscle), neither GLUT4 levels nor Rg' max. were reduced by 48 h fasting. GLUT1 was shown to be specifically expressed in cardiac myocytes, because intracellular vesicles enriched in GLUT4 contained significant levels of GLUT1. In conclusion, the high association of muscle GLUT4 content with insulin responsiveness in different muscles, and the preservation of both with fasting, supports a predominant role of GLUT4 in insulin-mediated glucose uptake. GLUT1 may play an important role in mediating cardiac muscle glucose uptake in the basal metabolic state. Marked changes in GLUT1 expression with alterations in the metabolic state, such as prolonged fasting, may play an important role in cardiac glucose metabolism. PMID- 8216231 TI - The kinetics of non-stoichiometric bursts of beta-lactam hydrolysis catalysed by class C beta-lactamases. AB - Class C beta-lactamases from Pseudomonas aeruginosa and several species of the Enterobacteriaceae have been observed to undergo a rapid burst in hydrolysis of beta-lactam antibiotics before relaxation to a steady-state rate of hydrolysis. The amplitude of the burst corresponds to the hydrolysis of between 1 and 10,000 mol of the substrate per mol of enzyme. The decay of the rate of hydrolysis in the burst phase comprises two exponential reactions, which indicates that there are three different reactive states of the enzymes. Examination of the kinetics of acylation by slowly reacting beta-lactams suggests that there are three forms of the free enzyme in slow equilibrium. Thus it would appear that the burst kinetics exhibited by class C enzymes can be attributed to redistribution of the enzyme between different conformations induced by the reaction with substrate. PMID- 8216232 TI - Involvement of the proteasome and antizyme in ornithine decarboxylase degradation by a reticulocyte lysate. AB - Ornithine decarboxylase (ODC) degradation in a freshly prepared reticulocyte lysate was examined. Immunodepletion of proteasomes from the reticulocyte lysate resulted in almost complete loss of ODC degradation. In contrast with the previously reported degradation in extracts of hepatoma tissue-culture (HTC) and Chinese-hamster ovary (CHO) cells or that by the purified 26 S proteasome, efficient degradation of ODC was observed in the lysate without exogenous antizyme, an ODC protein inhibitor induced by polyamines, owing to the presence of a significant amount of antizyme in the lysate. The degradation of ODC in the lysate was strongly suppressed on inactivation of antizyme in the lysate with antizyme inhibitor, a protein which binds to the antizyme and releases ODC from the ODC-antizyme complex. Thus the main pathway for ODC degradation in a reticulocyte lysate was essentially the same as that characterized previously in extracts of HTC and CHO cells, namely an ATP- and antizyme-dependent 26 S proteasome-catalysed pathway that is presumed to be responsible for ODC degradation in whole cells. PMID- 8216233 TI - Effect of L-ascorbic acid on the monophenolase activity of tyrosinase. AB - The effect of ascorbic acid on the monophenolase activity of tyrosinase, using tyrosine as substrate, has been studied. Over the ranges of ascorbic acid concentration used, no direct effect on the enzyme is found. However, a shortening of the characteristic induction period of the hydroxylation reaction is observed. The evolution of the reaction is dependent on the concentration of ascorbic acid. Low concentrations permit the system to reach the steady state when all ascorbic acid is consumed, whereas high concentrations do not. In the light of these results it is proposed that the influence of ascorbic acid on the reaction is due to its ability to reduce the enzymically generated o-quinones. A relationship between the ascorbic acid concentration, and the induction period generated by it, with the diphenolase activity of tyrosinase is established, which can be used as a basis for the determination of trace amounts of this reducing agent. PMID- 8216235 TI - Use of site-directed mutagenesis of allele-specific PCR primers to identify the GSTM1 A, GSTM1 B, GSTM1 A,B and GSTM1 null polymorphisms at the glutathione S transferase, GSTM1 locus. AB - We describe the identification of the GSTM1 null, GSTM1 A, GSTM1 B and GSTM1 A,B polymorphisms at the glutathione S-transferase GSTM1 locus using a single-step PCR method. Target DNA was amplified using primers to intron 6 and exon 7 with site-directed mutagenesis being used to introduce a restriction site in DNA amplified from GSTM1 *A, thereby allowing differentiation of this allele and GSTM1 *B. The accuracy of this approach in identifying the GSTM1 A, GSTM1 B, GSTM1 A,B and GSTM1 null polymorphisms was confirmed by comparison with, firstly, an established PCR method that distinguishes GSTM1 *0 homozygotes from individuals with the other GSTM1 genotypes and, secondly, GSTM1 phenotypes determined using chromatofocusing. PMID- 8216236 TI - Cytoplasmic pH regulates ATP-induced Ca(2+)-dependent K(+)-current oscillation in rat megakaryocytes. AB - The effect of cytoplasmic pH (pH(i)) on ATP-induced Ca2+ oscillation of rat megakaryocytes was investigated by the whole-cell patch-clamp technique. Megakaryocytes responded to extracellular ATP and showed the periodic activation of K+ channels, which reflects the oscillation in intracellular free Ca2+ concentration. Intracellular alkalinization by 20 mM NH4Cl resulted in inhibition of the oscillatory response, and intracellular acidification by 20 mM sodium acetate enhanced the response. NH4Cl also inhibited the Ins(1,4,5)P3-induced oscillation. Sodium acetate had no effect on the InsP3-induced oscillation, but enhanced the guanosine 5'-[gamma-thio]triphosphate-induced response. These results indicate that pH(i) modulates the ATP-induced cellular response at least at two points. PMID- 8216234 TI - Modulation of insulin secretion from normal rat islets by inhibitors of the post translational modifications of GTP-binding proteins. AB - Many GTP-binding proteins (GBPs) are modified by mevalonic acid (MVA)-dependent isoprenylation, carboxyl methylation or palmitoylation. The effects of inhibitors of these processes on insulin release were studied. Intact pancreatic islets were shown to synthesize and metabolize MVA and to prenylate several candidate proteins. Culture with lovastatin (to inhibit synthesis of endogenous MVA) caused the accumulation in the cytosol of low-M(r) GBPs (labelled by the [alpha-32P]GTP overlay technique), suggesting a disturbance of membrane association. Concomitantly, lovastatin pretreatment reduced glucose-induced insulin release by about 50%; co-provision of 100-200 microM MVA totally prevented this effect. Perillic acid, a purported inhibitor of the prenylation of small GBPs, also markedly reduced glucose-induced insulin secretion. Furthermore, both N-acetyl-S trans,trans-farnesyl-L-cysteine (AFC), which inhibited the base-labile carboxyl methylation of GBPs in islets or in transformed beta-cells, and cerulenic acid, an inhibitor of protein palmitoylation, also reduced nutrient-induced secretion; an inactive analogue of AFC (which did not inhibit carboxyl methylation in islets) had no effect on secretion. In contrast with nutrients, the effects of agonists that induce secretion by directly activating distal components in signal transduction (such as a phorbol ester or mastoparan) were either unaffected or enhanced by lovastatin or AFC. These data are compatible with the hypothesis that post-translational modifications are required for one or more stimulatory GBPs to promote proximal step(s) in fuel-induced insulin secretion, whereas one or more inhibitory GBPs might reduce secretion at a more distal locus. PMID- 8216237 TI - Daphnoretin, a new protein kinase C activator isolated from Wikstroemia indica C.A. Mey. AB - Daphnoretin, a biologically active principle isolated from Wikstroemia indica C.A. Mey., caused platelet aggregation in washed rabbit platelets, platelet-rich plasma and whole blood. The aggregation of and ATP release from platelets induced by daphnoretin were similar to phorbol ester- and diacylglycerol-induced aggregation and release. The EC50 values of daphnoretin-, phorbol 12,13 dibutyrate (PDBu)- and 1-oleoyl-2-acetylglycerol (OAG)-induced platelet aggregation in washed rabbit platelets were 17.2 +/- 2.8 microM, 20.6 +/- 2.1 nM and 38.6 +/- 1.7 microM respectively. Platelet aggregation induced by daphnoretin and PDBu was not inhibited by indomethacin, BN52021 or sodium nitroprusside. ADP scavenging systems, apyrase and phosphocreatine/creatine kinase, showed weak inhibition of the aggregation, and EGTA, triflavin, verapamil and prostaglandin E1 markedly inhibited the aggregation. Staurosporine, a potent protein kinase C inhibitor, suppressed daphnoretin-, PDBu- and OAG-induced aggregation and ATP release in a concentration-dependent manner. The IC50 values of staurosporine on daphnoretin (50 microM)-, PDBu (100 nM)- and OAG (50 microM)-induced aggregation were 37.7 +/- 8.3, 52.2 +/- 6.3 and 42.8 +/- 8.9 nM respectively. Daphnoretin did not cause significant thromboxane B2 formation in rabbit platelets. Neither daphnoretin nor PDBu caused [3H]inositol monophosphate formation or an increase in intracellular Ca2+ concentration in myo-[3H]inositol-labelled and Fura-2 loaded platelets. Platelet cytosolic protein kinase C was activated by daphnoretin and PDBu in a concentration-dependent manner with an EC50 of 12.4 +/- 1.2 microM and 18.7 +/- 1.4 nM respectively. Membrane-associated protein kinase C activity was increased by either daphnoretin or PDBu. [3H]PDBu binding to washed rabbit platelets was inhibited by daphnoretin in a concentration-dependent manner with an IC50 value of 45.2 +/- 5.2 microM. These results indicate that daphnoretin is a protein kinase C activator in rabbit platelets. PMID- 8216238 TI - Phosphorylation of bovine rod photoreceptor cyclic GMP phosphodiesterase. AB - The cyclic GMP phosphodiesterase (PDE) of retinal rods plays a key role in phototransduction and consists of two catalytic subunits (PDE alpha and PDE beta) and two identical inhibitory subunits (PDE gamma). Here we report that PDE alpha and PDE gamma are phosphorylated by protein kinase(s) C (PKC) from brain and rod outer segments (ROS). These same two types of PKC also phosphorylate PDE alpha in trypsin-activated PDE (without PDE gamma). In contrast, cyclic-AMP-dependent protein kinase catalytic subunit phosphorylates both PDE alpha and PDE beta, but not PDE gamma. This kinase does not phosphorylate trypsin-activated PDE. The synthetic peptides AKVISNLLGPREAAV (PDE alpha 30-44) and KQRQTRQFKSKPPKK (PDE gamma 31-45) inhibited phosphorylation of PDE by PKC from ROS. These data suggest that sites (at least one for each subunit) for phosphorylation of PDE by PKC are localized in these corresponding regions of PDE alpha and PDE gamma. Isoenzyme specific PKC antibodies against peptides unique to the alpha, beta, gamma, delta, epsilon and zeta isoforms of protein kinase C were used to show that a major form of PKC in ROS is PKC alpha. However, other minor forms were also present. PMID- 8216239 TI - Thimet oligopeptidase: similarity to 'soluble angiotensin II-binding protein' and some corrections to the published amino acid sequence of the rat testis enzyme. AB - The deduced amino acid sequence of pig liver soluble angiotensin II-binding protein [Sugiura, Hagiwara and Hirose (1992) J. Biol. Chem. 267, 18067-18072] is similar over most of its length to that reported for rat testis thimet oligopeptidase (EC 3.4.24.15) by Pierotti, Dong, Glucksman, Orlowski and Roberts [(1990) (Biochemistry 29, 10323-10329]. We have found that homogeneous rat testis thimet oligopeptidase binds angiotensin II with the same distinctive characteristics as the pig liver protein. Analysis of the nucleotide sequences reported for the two proteins pointed to the likelihood that sequencing errors had caused two segments of the amino acid sequence of the rat protein to be translated out of frame, and re-sequencing of selected parts of the clone (kindly provided by the previous authors) confirmed this. The revised deduced amino acid sequence of rat thimet oligopeptidase contains 687 residues, representing a protein of 78,308 Da, and is more closely related to those of the pig liver protein and other known homologues of thimet oligopeptidase than that described previously. PMID- 8216240 TI - Malonyl-CoA metabolism in cardiac myocytes and its relevance to the control of fatty acid oxidation. AB - 1. Viable myocytes were obtained from rat hearts. Oxidation of [1-14C]palmitate by these cells could be decreased by the addition of glucose (5 mM) or lactate (2 mM). In the presence of glucose, insulin decreased and adrenaline increased palmitate oxidation. 2. The myocytes contained activities of ATP citrate-lyase, acetyl-CoA carboxylase and the condensing enzyme of the fatty acid elongation system. No fatty acid synthase activity was demonstrable in myocytes. 3. In rat hearts perfused with 5 mM glucose, malonyl-CoA content was acutely raised by insulin. In the presence of glucose+insulin, perfusion with palmitate or adrenaline decreased the malonyl-CoA content. 4. It is concluded that malonyl-CoA can be synthesized within cardiac myocytes and that the level of this metabolite can be acutely regulated. This is likely to have consequences for the regulation of carnitine palmitoyltransferase in the heart. PMID- 8216241 TI - Differential control of the functional cell surface expression and content of hexose transporter GLUT-1 by glucose and glucose metabolism in murine fibroblasts. AB - The present paper evaluates the contributions of glucose and its metabolites to the post-translational regulation of hexose transport and GLUT-1 content in murine fibroblasts. The effects of 3-O-methylglucose, a nearly non-metabolizable glucose analogue, on 2-deoxyglucose-uptake, cell-surface expression and content of GLUT-1, glucose 6-phosphate levels, and phosphoglucose isomerase (PGI) and hexokinase activities of murine fibroblasts were compared with those of glucose and fructose. Glucose (EC50 approximately 6 mM) or 3-O-methylglucose (EC50 approximately 12 mM), which are substrates of GLUT-1, but not fructose, which is not transported by GLUT-1, are able to prevent the glucose-deprivation-induced increases in both hexose transport and cell-surface expression of GLUT-1. In contrast, glucose (EC50 approximately 6 mM), but not 3-O-methylglucose or fructose, prevents the glucose-deprivation-induced accumulation of total GLUT-1 polypeptides. Glucose (> or = 5 mM), but not fructose or 3-O-methylglucose, leads to significant glucose 6-phosphate accumulation. Although 3-O-methylglucose is weakly phosphorylated by fibroblasts, accumulation of phosphorylated product does not correlate with hexose-transport regulation. The activities of hexokinase and PGI are not altered by glucose, fructose or 3-O-methylglucose. We suggest that, in murine fibroblasts: (i) hexose transport and GLUT-1 content are differentially regulated; (ii) substrates of GLUT-1 and/or their immediate metabolites regulate the cell-surface expression of functional GLUT-1; and (iii) glucose metabolism is required for the regulation of GLUT-1 content. PMID- 8216243 TI - Interaction of pyrene-labeled monosialoganglioside GM1 micelles with cholera toxin. AB - Monosialoganglioside GM1 labeled with 1-pyrene-dodecanoic acid was used to monitor interactions between cholera toxin and its receptor. Binding of cholera toxin to labeled ganglioside caused a decrease in pyrene fluorescence intensity at 480 nm concomitant with an increase in fluorescence intensity at 380 and 398 nm. The observed fluorescence changes are similar to those observed when fluorescent ganglioside is moved from an aqueous solvent to an organic solvent. The data are consistent with cholera toxin-bound ganglioside undergoing a process resembling solvent-dependent molecular dispersion. PMID- 8216242 TI - Modelling of the serine-proteinase fold by X-ray and neutron scattering and sedimentation analyses: occurrence of the fold in factor D of the complement system. AB - Solution scattering is a powerful means of determining the overall arrangement of domains in the multidomain proteins of complement. the serine-proteinase domain is central to all proteolytic events during complement activation. As models of this domain, bovine beta-trypsin, trypsinogen, alpha-chymotrypsin and chymotrypsinogen A were studied by neutron and X-ray synchrotron solution scattering. At pH 7, all the X-ray and neutron M(r) values corresponded to monomeric proteins. The X-ray radii of gyration, RG, of beta-trypsin, trypsinogen, alpha-chymotrypsin and chymotrypsinogen A (measured in positive solute-solvent contrasts) were 1.59 nm, 1.78 nm, 1.71 nm and 1.76 nm (+/- 0.05 0.11 nm) in that order. Neutron contrast variation showed that the RG at infinite contrast, RC, for these four proteins were 1.57 nm, 1.70 nm, 1.67 nm and 1.78 nm (+/- 0.03 nm) in that same order. The radial inhomogeneity of neutron-scattering density, alpha, was positive at (5-13) x 10(-5), and corresponds to the preponderance of hydrophilic residues near the protein surface. On trypsinogen activation, a small reduction in the RG value of 0.13 +/- 0.07 nm was just detectable, while the RG of chymotrypsinogen A was unchanged after activation. The RC and alpha values of the four proteins can be calculated by using crystallographic co-ordinates. The reduced RG of beta-trypsin relative to trypsinogen was explained in terms of the removal of the extended N-terminal hexapeptide of trypsinogen. The full X-ray and neutron-scattering curves in positive and negative contrasts agreed well with scattering curves calculated from crystallographic coordinates to a nominal structural resolution of 4.5 nm, provided that the internal structure was considered in neutron modelling, and that the hydration was considered in X-ray modelling. Sedimentation-coefficient data also provide information on the disposition of domains in multidomain proteins. It was found that the hydrated X-ray sphere model could be directly utilized to calculate sedimentation coefficients. X-ray scattering on factor D showed from its RG of 1.78 nm that this is monomeric and very similar in structure to beta-trypsin. The X-ray-scattering curve of factor D was readily modelled using the beta-trypsin crystal structure after allowance for sequence changes. The success of these modellings provides a basis for the constrained modelling of solution scattering data for the multidomain proteins of complement. PMID- 8216244 TI - Use of hybridization for distance measurement by fluorescence energy transfer in oligomeric proteins: distance between two functional sites in aspartase. AB - Our previous studies suggested that in a tetrameric enzyme aspartase, Cys-140 and Trp-430 are located at or near the catalytic and activator sites, respectively. To estimate the distance between these two sites, fluorescence energy transfer between a single tryptophan (Trp-430) and a fluorescent group specifically attached to Cys-140 has been measured. From the fluorescence spectra of the enzyme, the distance was calculated to be 22.2 A according to the Forster's theory. To estimate the contribution of energy transfer between subunits, we prepared hybrids composed of non-fluorescent and fluorescent subunits and showed that the energy transfer occurred mainly within one subunit in the tetramer. These results indicate that the use of hybridization is very effective as a general method for evaluation of intersubunit energy transfer in oligomeric proteins. PMID- 8216245 TI - Increased replication of simian immunodeficiency virus in CEM x174 cells by morphine sulfate. AB - Infection with simian immunodeficiency virus induces cytopathic effects on CEM x174 cells in vitro. Syncytium formation of SIV-infected CEM x174 cells was significantly enhanced in the presence of morphine sulfate, with a concomitant increase in the activity of cellular reverse transcriptase and in the expression of SIV p27 core antigen. Parallel establishment of the viability of the morphine treated cells indicates that the short-acting opioid protects against cell lysis induced by SIV so that replication and production of SIV particles continued and exceeded those without morphine treatment. This delayed cell lysis induced by morphine as seen in vitro correlated with an in vivo observation that peripheral blood mononuclear cells isolated from morphine-treated rhesus macaques displayed a less degree of programmed cell death by apoptosis during early stages of SIVmac infection. These studies suggest that the modification of the biological properties of HIV-infected cells by morphine sulfate may be one of the mechanisms by which opioids exacerbate the progression of HIV in drug abusers. PMID- 8216246 TI - Efficient adenovirus-mediated gene transfer into human blood monocyte-derived macrophages. AB - The efficiency of gene transfer into human blood monocyte-derived macrophages has been evaluated using a replication-defective adenovirus vector harboring a lac Z gene of E. coli as a reporter gene. Whereas, no beta-galactosidase activity was found in freshly infected purified monocytes, 40% to 80% of infected macrophages which derived from these monocytes showed a beta-galactosidase activity, 2 to 4 days after infection and lasted for at least 3 weeks. Moreover, beta galactosidase activity was found in infected monocyte/macrophages 7 days after their injection into a human tumor preestablished in nude mice. These data indicate that it is possible to transfer and stably express a gene of potential therapeutical function into human monocyte-derived macrophages using an adenovirus vector. PMID- 8216247 TI - Effects of the progestin antagonist RU 486 on T-47D breast cancer cell cycle kinetics and cell cycle regulatory genes. AB - Possible mechanisms by which the progestin antagonist RU 486 inhibits cell growth were investigated by comparing the effects of the antiprogestin with those of progestin and antiestrogen. Exposure of T-47D breast cancer cells to RU 486 caused a decline in the proportion of cells in S phase, indicative of a block to cell cycle progression in G1 phase. This was accompanied by a marked decrease in c-myc expression but no change in cyclin D1 expression. The cell kinetic data suggest that progestin antagonist inhibition of proliferation and progestin stimulation of proliferation are mediated by opposing effects on the same mechanism. Both estrogen antagonists and progestin antagonists appear to act at a similar part of G1 phase but there are clear differences in their effects on cyclin D1 expression, suggesting that the mechanisms by which these compounds inhibit proliferation are distinct. PMID- 8216248 TI - In vivo spin trapping of nitric oxide in mice. AB - We report here an in vivo spin-trapping technique combined with electron paramagnetic resonance (EPR) spectroscopy to measure nitric oxide (.NO) production in the blood circulation of conscious mice. The method is based on the trapping of nitric oxide (.NO) by a metal-chelator complex consisting of N-methyl D-glucamine dithiocarbamate (MGD) and reduced iron (Fe2+) to form a stable and water-soluble [(MGD)2-Fe(2+)-NO] complex, which gives rise to a characteristic three-line EPR spectrum of a mononitrosyl-Fe2+ complex (aN = 12.5 G and g(iso) = 2.04) at ambient temperatures. After simultaneous intravenous injection of sodium nitroprusside (an .NO donor) and the [(MGD)2-Fe2+] complex into the lateral vein of the mouse tail, the appearance of the three-line spectrum in the blood circulation of the mouse tail was monitored continuously by using an S-band EPR spectrometer, operating at 3.5 GHz. This represents the first spin trapping of .NO in living animals. PMID- 8216249 TI - Crystal matrix protein is related to human prothrombin. AB - Crystal matrix protein (CMP) is the principal protein found in calcium oxalate (CaOx) crystals precipitated from whole human urine. It is a potent inhibitor of crystal aggregation and may therefore be important in the aetiology of kidney stone disease. CMP was isolated from CaOx crystals by EDTA dissolution and purified by Sephacryl S-200 column chromatography and reversed-phase high pressure liquid chromatography. Edman degradation revealed 81.8% sequence identity of the 11 N-terminal amino acids of CMP with the N-terminus of human prothrombin, which contains 10 gamma-carboxyglutamic acid residues in the first 32 amino acids. The apparent relationship between CMP and prothrombin was confirmed when an antibody to human prothrombin reacted with CMP upon Western blotting of sodium dodecyl sulphate polyacrylamide gels of the protein. PMID- 8216250 TI - The mechanism for apo-B mRNA editing is deamination. AB - Apolipoprotein (apo-) B mRNA editing at nucleotide 6666 converts cytidine to uridine, transforming the codon for glutamine-2153 to a termination codon. To investigate this editing mechanism, [a-32P] and [5-3H] CTP were incorporated into synthetic apo-B RNA. After the substrate had been edited extensively in vitro by a partially purified editing extract, the edited base was isolated and analyzed for radioactivity. The uridine-6666 resulting from the editing reaction had the same ratio of 3H to 32P as did the cytidine-6666, demonstrating that deamination rather than base exchange or nucleotide replacement is the mechanism for apo-B mRNA editing. PMID- 8216251 TI - Cloning and functional expression of a Schistosoma japonicum cDNA homologous to the enolase gene family. AB - A cDNA encoding the complete open reading frame of Schistosoma japonicum enolase has been cloned. The 1494bp cDNA (C30) was isolated from a S. japonicum cDNA expression library immunoscreened with hyperimmune rabbit sera raised against soluble adult S. japonicum proteins. The ORF encodes a protein of 434 amino acids exhibiting 72% identity to human, murine, and rat enolases, and 62% identity to Saccharomyces cerevisiae enolase. The inferred molecular mass of the protein is 47,251 Daltons, similar to that reported for the enolases of other species. In vitro translation of C30 also generated a protein of 47kDa. After subcloning and expression, the recombinant protein was purified by affinity chromatography under non-denaturing conditions and shown to exhibit functional enolase enzymatic activity. PMID- 8216252 TI - The effect of 75% glycerol on the oxygen binding properties of carp hemoglobin. AB - At pH 6 in the presence of inositol hexaphosphate, IHP, conditions where ligand saturated carp hemoglobin is already in the low affinity T state, the addition of glycerol has little effect on affinity and ligand binding remains noncooperative. At all other pH values examined, with and without IHP, the effect of glycerol is to lower oxygen affinity possibly by shifting the equilibrium between the T state and the high affinity R state in the direction of the T state. Although glycerol does not appear to have an appreciable effect on the T state itself, a small effect on the R state cannot be excluded by our data. PMID- 8216253 TI - Selective inactivation of glyceraldehyde-3-phosphate dehydrogenase by vinyl sulfones. AB - Incubation of glyceraldehyde-3-phosphate dehydrogenase with vinyl sulfones resulted in a pseudo first-order loss of enzyme activity. The selective inactivation of the enzyme by vinyl sulfones is suggested from the structural requirement analysis and the enzyme susceptibility test. The enzyme inactivation was strongly reduced in the presence of NAD or glyceraldehyde-3-phosphate, and the prior treatment of the enzyme with 5,5'-dithio-bis-(2-nitrobenzoic acid) prevented the enzyme from the inactivation by vinyl sulfones (> or = 90%). Moreover, the early rapid phase of inactivation was much more responsive to L cysteine reactivation, compared with the slower phase. Based on these results, it is proposed that vinyl sulfones inactivate the enzyme by inducing the oxidation of cysteine residue and/or covalent binding to cysteine residue in active site. PMID- 8216254 TI - Thyrotropin stimulates invasion and growth of follicular thyroid cancer cells via PKC- rather than PKA-activation. AB - The signal transduction of TSH in invasion and growth of FTC 133, a human follicular thyroid cancer cell line, was investigated. TSH (0.01-1 mIU/ml) stimulated invasion of FTC 133 by 21% and growth by 20% of basal. Cyclic AMP stimulators and inhibitors had no effect at any concentration. The PKC-agonist TPA enhanced invasion and growth by 15%, whereas staurosporine, a PKC-antagonist, inhibited them by 32% and 60%, respectively. The latter also reversed TSH stimulation. EGF enhanced invasion (42%) and growth of FTC 133 (25%). Staurosporine did not reverse EGF stimulation. The tyrosine kinase antagonist genistein reversed EGF, but not TSH stimulation. Pertussis toxin inhibited invasion (18%) and growth (22%). Cholera toxin was less inhibitive. We demonstrated for the first time, that TSH stimulates invasion and growth of human thyroid cancer cells in vitro by PKC- rather than PKA-stimulation. PMID- 8216255 TI - Fluorescence properties of the three tyrosine residues in the ribose-binding protein. AB - Three tyrosine residues but no tryptophan exist in the ribose-binding protein (RBP) of Escherichia coli. In order to assess the contribution of each tyrosine to the fluorescence properties, mutants were constructed by site-directed mutagenesis to replace tyrosines at 32, 115, and 261 by phenylalanines. The mutant proteins were functional as confirmed by in vivo tactic response and by their ability to bind to ribose. The fluorescence emission spectra of the native proteins purified from the various tyrosine mutants were measured from emission scans with a peak at 303 nm. The tyrosines, at positions 32, 115, and 261, contribute 10.0, 69.6, and 23.4%, respectively, to the total intensity of fluorescence. In completely unfolded polypeptide, these tyrosines have almost the same intensities of fluorescence, indicating that the fluorescence from tyrosines at 32 and 261 are considerably quenched in the folded, native protein. PMID- 8216256 TI - The majority of osteoclasts require mRNA and protein synthesis for bone resorption in vitro. AB - Mithramycin is an mRNA synthesis inhibitor that has been used to decrease bone resorption in patients with humoral hypercalcemia and Paget's disease. During studies on the mechanism of action of mithramycin it became clear that the compound has a direct inhibitory effect on osteoclastic bone resorption in the in vitro bone slice assay. At concentrations of 0.1-100 nM mithramycin directly inhibited osteoclastic bone resorption dose-dependently up to 66 +/- 5% at 100 nM (mean +/- SEM, 3 expts.). Another mRNA synthesis inhibitor, actinomycin D (0.1 100 nM) and the protein synthesis inhibitor, cycloheximide (0.1-10 microM), also dose-dependently inhibited osteoclastic bone resorption by 78 +/- 7% at 100 nM and 76 +/- 7% at 10 microM, respectively. Mithramycin and actinomycin D at 100 nM did not affect osteoclast survival on bone slices and were therefore not cytotoxic at the concentrations used. Mithramycin (100 nM) and cycloheximide (10 microM) both slightly decreased osteoclast cytoplasmic spreading. Addition of 100 nM mithramycin 6 hr after osteoclast adhesion to bone slices still inhibited subsequent resorption by 50%, indicating a continued but lesser requirement for mRNA synthesis during bone resorption. These results show that approximately 75% of osteoclasts obtained from neonatal rat long bones are activated by adhesion to mineralized bone surfaces and require mRNA and protein synthesis in order to resorb bone in vitro. PMID- 8216257 TI - Vesnarinone inhibits production of HIV-1 in cultured cells. AB - Vesnarinone, a synthetic oral cardiotonic agent that has been used for treatment of patients with congestive heart failure, was found to inhibit replication of HIV-1 in a peripheral blood lymphocytes model and in chronically infected macrophages at clinically achieved concentrations. Vesnarinone has no direct inhibitory activity against the reverse transcriptase of HIV-1, syncytium formation in short term assays, or retroviral protease. In addition, vesnarinone inhibits production of TNF-alpha and IL-6 by human peripheral blood mononucleated cells stimulated with LPS. These observations suggest that vesnarinone may be therapeutically useful in patients infected with HIV-1. PMID- 8216258 TI - The presence of Ca(2+)-independent phospholipase A1 highly specific for phosphatidylinositol in bovine brain. AB - EDTA-insensitive phospholipase A activity hydrolyzing phosphatidylinositol was detected in a bovine brain soluble fraction. This phospholipase A was purified 25 fold by sequential chromatographies of DEAE-Toyopearl, Phenyl-Toyopearl, and Ultrahydrogel 1000. The partially purified EDTA-insensitive phospholipase A showed an apparent molecular mass of 230kDa on an Ultrahydrogel 1000 column in the presence of 0.05% Triton X-100 and a pH optimum at 7.0. The enzyme was highly specific for phosphatidylinositol; phosphatidylethanolamine and phosphatidylcholine were not hydrolyzed significantly. The enzyme activity was characterized as phospholipase A1, and Ca2+ and Mg2+ were not required for its activity. These results indicate the existence of Ca(2+)-independent, phosphatidylinositol-specific metabolism besides those catalyzed by Ca(2+) dependent phospholipase A2 and Ca(2+)-dependent, phosphatidylinositol-specific phospholipase C. PMID- 8216260 TI - Sperm motility loss induced by gossypol: relation with OH. scavengers, motile stimulators and malondialdehyde production. AB - Aerobic incubation of rat spermatozoa in a balanced salt solution containing 10 microM of gossypol produced a loss of sperm motility. This effect was not reverted by the presence of 25 mM Theophylline, a well-known stimulant of motility, but was significantly diminished by the addition of 10 mM Mannitol. As mannitol is a superoxide scavenger and we found a close correlation between the loss of sperm motility and the malondialdehyde production, we concluded that gossypol affect rat spermatozoa by producing a peroxidative breakdown of membrane phospholipids. PMID- 8216259 TI - A new myosin I gene in Drosophila. AB - We have identified and cloned a new myosin-I cDNA, myosin 61F, from Drosophila melanogaster. The sequence of myosin 61F cDNA shows high similarity to vertebrate myosin-I sequences. Myosin 61F is most similar to bovine myosin Ib, showing 78% similarity and 63% identity. Myosin 61F is a single copy gene which maps to polytene region 61F, a genomic region with several potential myosin mutations. The identification of a myosin-I gene in Drosophila will allow genetic analysis of myosin-I function in a metazoan organism. PMID- 8216261 TI - High, stable expression of the bovine histamine H1-receptor coupled to [Ca2+]i mobilisation in CHO-K1 cells. AB - The bovine H1-receptor DNA was transfected into Chinese hamster ovary cells (CHO K1) using an expression vector. Binding studies revealed very high expression levels of the receptor which was found to have a Kd for [3H]-mepyramine of 1 nM. Addition of histamine resulted in a concentration-dependent increase in intracellular calcium which was found to involve both release from intracellular stores and entry across the plasma membrane. Furthermore, the response demonstrated the pharmacological characteristics of an H1-receptor-mediated event. Thus, we present the first report of the high, functional expression of the bovine H1-receptor coupled to mobilisation of intracellular calcium in CHO-K1 cells. PMID- 8216262 TI - Interaction of 2-thio-5-fluoro-dUMP and 4-thio-5-fluoro-dUMP with mammalian normal and tumour and helminthic thymidylate synthases: influence of C(4) substituents on specificity for enzyme inactivation. AB - To determine how 5-fluoro-dUMP modifications may affect its specificity, 2-thio-5 fluoro-dUMP and 4-thio-5-fluoro-dUMP were compared as inhibitors of thymidylate synthases isolated from parental and FdUrd-resistant mouse leukemia L1210 cells, human and rat colon adenocarcinomas, regenerating rat liver and the tapeworm, Hymenolepis diminuta, differing in sensitivity to time- and N5,10 methylenetetrahydrofolate-dependent inactivation by 5-fluoro-dUMP (Ki values ranging from 10(-9) to 10(-7) M). Inactivation by 2-thio-5-fluoro-dUMP, relative to 5-fluoro-dUMP, was 5-20-fold weaker, with specificity for inactivation of different thymidylate synthases paralleling that of 5-fluoro-dUMP. By contrast, 4 thio-5-fluoro-dUMP showed very different specificity, being as potent an inactivator for some enzymes as 5-fluoro-dUMP, but 45-85-fold weaker for others. The results suggest that an interplay between substituents at C(4) and C(5) of the pyrimidine ring may affect the specificity of thymidylate synthase inactivation. PMID- 8216263 TI - Sequential alterations in tRNA population of 2-acetylaminofluorene-induced hepatocyte nodules. AB - In order to investigate the possible mechanisms by which cellular alterations can start an altered onco-developmental gene expression, we studied tRNA distribution profiles during the early steps of 2-acetylaminofluorene-induced hepatocarcinogenesis. The finding of progressive and sequential alterations appears to support the hypothesis of a causal connection between tRNA changes and nodular cell proliferation, possibly through the disruption of the mechanism which regulates tRNA functional adaptation. PMID- 8216264 TI - The Rap1A protein enhances protein kinase C activity in vitro. AB - The low molecular weight G protein Rap1A constitutes a major fraction of the GTP binding proteins found in the plasma membrane and specific granules of the neutrophil; however, the function of Rap1A in neutrophil responses remains unclear. Protein kinase C assays were performed to examine the effects of Rap1A on protein kinase C activity. In the presence of recombinant Rap1A, the phosphorylation of protein kinase C substrates was significantly enhanced. The effect of the Rap1A on protein kinase C activity was concentration-dependent and specific. The low molecular weight G protein Rac 2 had no effect on protein kinase C activity. These results suggest that Rap1A may interact with protein kinases and regulate signal transduction. PMID- 8216265 TI - P-cadherin and E-cadherin are co-expressed in MDCK cells. AB - The Madin-Darby canine kidney (MDCK) cell line is a valuable model of epithelial cell function and the role of E (epithelial)-cadherin in MDCK cell activity is well-appreciated. Northern and immunoblot analyses were used here to demonstrate that, in addition to E-cadherin, MDCK cell cultures also express P(placental) cadherin. Immunocytochemistry was then used to compare the localization and detergent extractability of P- and E-cadherin. While both cadherins were found at areas of cell-cell contact, the relative ease with which P-cadherin could be extracted suggests a weaker anchorage to the actin cytoskeleton than has been demonstrated for E-cadherin, and may correspond to less permanent cell-cell interactions than those attributed to E-cadherin. The co-expression of different cadherins by MDCK cells has not been fully explored and may influence interpretations of MDCK cell function that previously considered only the activity of E-cadherin. PMID- 8216266 TI - Establishment of radioimmunoassay for human neutrophil peptides and their increases in plasma and neutrophil in infection. AB - Neutrophil peptide, also called defensin, is an antimicrobial peptide localized in azurophil granules in neutrophils. Using a synthetic human neutrophil peptide 1 (HNP-1), we prepared an antiserum against the peptide and established a highly sensitive radioimmunoassay (RIA). This RIA equally recognized HNP-1, -2, and -3 on a molar basis. Analyses of leukocyte and blood extracts obtained from normal individuals and patients with bacterial infection by reverse-phase high performance liquid chromatography coupled with the RIA showed that the antiserum specifically detected HNP molecules. Concentrations of HNP 1-3 in total in normal human blood and plasma are 13.2 +/- 1.4 (mean +/- SEM) ng/mu 1 and 403.8 +/- 38.9 pg/mu 1, respectively. The values increased in infection and returned to within the normal levels after the recovery of the disorder. Granulocyte colony stimulating factor (G-CSF) increased the plasma and blood concentrations of HNP 1 3. The RIA established here provides a useful tool to elucidate the pathophysiological significance of HNP and to evaluate the neutrophil functions in infection and inflammation. PMID- 8216267 TI - RXR-independent action of the receptors for thyroid hormone, retinoid acid and vitamin D on inverted palindromes. AB - Hydrophobic ligands, like all-trans and 9-cis retinoic acid (RA), 3,5,3' triiodothyronine (T3) and 1,25-dihydroxy-cholecalciferol (VD), mediate their biological response by binding to their respective nuclear receptors (RARs, RXRs, T3Rs and VDRs) which are members of the steroid receptor superfamily. These ligand-dependent transcription factors bind as dimers to specific DNA sequences known as hormone response elements. The specificity of the receptor complexes for response elements is dictated by their discrimination of half-site sequences, their distance and their relative orientation. Here, RXR-independent transactivation of VDRs, T3Rs, and RARs and their in vitro DNA binding to various response elements were investigated. The data indicate that functional response elements can consist of direct repeats, palindromes and inverted palindromes. A sterical link between the optimal spacers of direct repeats and inverted palindromes is suggested. PMID- 8216268 TI - The nitric oxide donor, S-nitroso-N-acetyl-penicillamine, inhibits secretory activity in rat isolated parietal cells. AB - Accumulation of the weak base aminopyrine was used as an index of acid secretory activity in rat isolated parietal cells. The nitric oxide (NO) donor, S-nitroso-N acetyl-penicillamine (SNAP) caused a dose-dependent inhibition of aminopyrine accumulation (half-maximally effective concentration 247 microM) which was accompanied by an increase in guanosine 3',5'-cyclic monophosphate (cGMP) but no decrease in cell viability (trypan blue), glucose oxidation or adenosine 3',5' cyclic monophosphate (cAMP) content. Oxyhaemoglobin (37 microM), which scavenges NO, significantly reduced the inhibitory effect of SNAP (1 mM). Prior exposure of intact cells to SNAP also reduced aminopyrine accumulation in response to ATP in permeabilised cells, an effect prevented by Rp-8-bromoguanosine 3',5' monophosphorothioate, which inhibits activation of cGMP-dependent protein kinase, but not by the Sp-isomer. NO thus inhibits secretory activity in rat parietal cells by a specific interaction that may involve cGMP. PMID- 8216269 TI - PCR cloning and sequence of the murine GPIIb gene promoter. AB - The promoter region of the murine GPIIb gene was cloned by PCR using oligonucleotides corresponding to the human gene promoter. Analysis of the sequence revealed homologies among species and the conservation of DNA motifs which could be implicated in the regulation of the gene. Transfection experiments show that the murine promoter contains informations for a tissue specific expression of the gene in megakaryocytic cell lines. PMID- 8216270 TI - Further evidence for both functional and structural microcompartmentation within the membranes of two associated organelles, mitochondrion and endoplasmic reticulum. AB - We previously demonstrated that the translocation of phospholipids between the mitochondrion and the endoplasmic reticulum occurs via highly specialized membrane microdomains of both organelles that are in situ closely associated. As understanding of the interactions between both organelles requires characterization of the translocation sites organization, we first analysed the amino acid compositions of these sites. Using principal component analysis, we have shown that the translocation sites exhibit characteristic patterns when compared with the membranes from which they are derived. The results are discussed in terms of both functional and structural microcompartmentation within the membranes of mitochondria and endoplasmic reticulum. PMID- 8216272 TI - Potassium channels regulate cholecystokinin secretion in STC-1 cells. AB - Following blockade of plasma membrane potassium channels with barium or tetraethylammonium chloride, release of cholecystokinin was increased in an intestinal cell line (STC-1). Treatment with calcium channel blockers inhibited barium- or TEA-induced secretion. Barium chloride also stimulated 45Ca efflux from STC-1 cells. Whole cell patch clamp recordings revealed a voltage-activated, L-type calcium current. We conclude that, inhibition of basally active potassium channels may depolarize STC-1 cells, producing activation of voltage-gated calcium influx pathways. Influx of calcium may lead to a release of intracellular calcium which stimulates cholecystokinin secretion. PMID- 8216271 TI - Expression of an EF-1 alpha-like rat cDNA, S1, in E. coli and production of a rabbit polyclonal antiserum to the recombinant protein. AB - A previously identified rat cDNA (S1) that shares 78% nucleotide homology and a predicted 92% amino acid homology with human EF-1 alpha was constructed into PGEX 2T and inducibly expressed in E. coli as a fusion protein. The purified recombinant S1 protein (rpS1) was used to raise rabbit antiserum which recognized rpS1 but not EF-1 alpha on immunoblots. A polyclonal antiserum to EF-1 alpha failed to react with the rpS1. Our results indicate that rpS1 protein can be used to produce antibodies which distinguish pS1 from EF-1 alpha despite their extensive amino acid sequence homology. PMID- 8216273 TI - cDNA cloning, expression in Escherichia coli and purification of human 6-pyruvoyl tetrahydropterin synthase. AB - cDNA clones for human 6-pyruvoyl-tetrahydropterin synthase, the second enzyme in the biosynthetic pathway of tetrahydrobiopterin, were isolated from a human Molt 4 cell cDNA library by cross-hybridization with a rat cDNA. One cDNA clone contained the entire coding sequence of 435 base pairs. The cDNA was expressed in Escherichia coli using the expression vector pMAL as a fusion protein with maltose-binding protein. After affinity purification through its maltose-binding protein domain, the fusion protein was digested by factor Xa at a specific cleavage site inserted between the domains. The main product was a protein species with a native molecular mass of 90 kDa and a subunit molecular mass of 17 kDa, and the molecular masses and its kinetic properties were similar to those of the human enzyme purified from the liver. PMID- 8216274 TI - Pre-messenger RNA splicing of transcripts synthesized from human small nuclear RNA gene promoters. AB - In order to explore the coupling of transcription with splicing in mammalian cells we have prepared hybrid genes in which either the human U2 promoter, recognized by RNA polymerase II, or the human U6 promoter, recognized by RNA polymerase III, was fused to an intron-containing gene segment. Neither human small nuclear RNA gene contains an intron although U6 genes from some species of yeast contain a short intervening sequence. Following transfection of human cells and analysis of specific RNAs by primer extension we found that the chimeric U2 promoter-derived transcript was efficiently spliced but the RNA polymerase III transcript driven by the U6 promoter remained unspliced. Hence, the splicing apparatus differentiates between transcripts produced from two closely related promoters that are distinguished by RNA polymerase selectivity. PMID- 8216275 TI - Macrophage colony-stimulating factor (M-CSF) induces migration in osteoclasts in vitro. AB - It has recently been shown that M-CSF is essential for osteoclast formation and survival. Paradoxically, the cytokine inhibits bone resorption by isolated osteoclasts. This implies that it may stimulate some function in osteoclasts not directly related to the bone resorptive process itself. We now report that M-CSF stimulates migration in isolated rat osteoclasts. This was achieved predominantly by a 3-8-fold increase in the proportion of osteoclasts demonstrating migration, combined with an increase in the area of substrate covered (43-96%) by each migrating cell. This action of M-CSF on migration is the inverse of its effect on resorption, wherein it has been previously found to reduce the proportion of osteoclasts that resorb bone and suggests that migration and resorption might represent alternative states of osteoclast behaviour. The results also suggest that osteoblast-derived M-CSF might play a role in the induction and regulation of localisation of these cells in bone. PMID- 8216276 TI - Chenodeoxycholic acid-dependent induction of major histocompatibility complex class I mRNA expression in a human hepatoma cell line. AB - Primary biliary cirrhosis is known as an autoimmune chronic cholestatic disease and characterized by various immunological abnormalities. Especially, the aberrant expression of major histocompatibility complex (MHC) class I antigens on hepatocytes has been considered to have a pivotal role in the pathogenesis and progression of the disease. However, the underlying mechanism of this aberrant expression of MHC class I molecules has not yet been clarified. In the present study we showed that MHC class I immunoreactivities were increased by treatment with chenodeoxycholic acid (CDCA) in the human hepatoma cell line HLE. Moreover, CDCA treatment of the cells increased the steady-state levels of MHC class I mRNA. Since CDCA is one of major constituents of endogenous bile acids in cholestasis, these results suggest that intrahepatic cholestasis, which is almost inevitably associated with PBC, increases both production and surface expression of MHC class I antigens in hepatocytes. PMID- 8216277 TI - Histidine residues are involved in translocation-coupled ATP hydrolysis by the Sec-A protein. AB - Treatment of SecA, an essential component of the protein translocation machinery of Escherichia coli, with a histidine-specific reagent, diethylpyrocarbonate, caused significant abolition of its translocation-coupled ATPase (translocation ATPase) activity, which requires a presecretory protein and membrane vesicles, whereas its endogenous ATPase (SecA-ATPase) activity was enhanced by a factor of 2. Diethylpyrocarbonate-treated SecA exhibited an absorption maximum at 240 nm due to the formation of N-carbethoxyhistidine. Upon the modification of about 5 of the total 22 histidine residues in the SecA molecule, both the abolition of its translocation ATPase activity and the enhancement of its SecA-ATPase activity occurred. Intact and modified SecA exhibited similar affinities for ATP, proOmpA and membranes, whereas Vmax of the translocation ATPase activity was significantly lower in the case of the modified SecA. ATP had no effect on the modification of SecA. Taken together, these results indicate that histidine residues susceptible to diethylpyrocarbonate are essential for the translocation ATPase, but not directly involved in the binding of ATP, proOmpA and membranes. A possible reason for the abolition of translocation ATPase is discussed. PMID- 8216278 TI - Clonal analysis for developmental potential of chick periosteum-derived cells: agar gel culture system. AB - The developmental potential of periosteum-derived cells was clonally assessed with an agar gel culture system. Morphologically, two types of colonies were predominantly observed. By immunocytochemical observation with antibodies against aggrecan or bone Gla protein, one type of colony was judged to be chondrogenic, and the other osteogenic. By chronological observation, each type of colony did not convert to the other. Supplementation with transforming growth factor (TGF) beta 1 shortened the time course of chondrogenesis and also increased colony forming efficiency of chondrogenic colonies. On the other hand, colony forming efficiency of osteogenic colonies decreased with TGF-beta 1 treatment, whereas the time course of osteogenesis remained unaffected. These observations suggest that there are both committed osteoprogenitor and chondroprogenitor cells present in the periosteal cell population, and TGF-beta 1 stimulates proliferation and differentiation of chondrogenic cell population by its targeted action. PMID- 8216279 TI - Mutagenesis of bacteriophage IKe major coat protein transmembrane domain: role of an interfacial proline residue. AB - The transmembrane (TM) domain of the 53-residue major coat protein of the M13 related bacteriophage IKe (residues 24-42: LISQTWPVVTTVVVAGVLI) has been subjected to randomized mutagenesis to probe the conformation and stability of the TM domain, as well as the effect of structurally-important residues such as proline. TM mutants were obtained by the Eckstein method of site-directed mutagenesis using the IKe genome as template so as to eliminate the need for subcloning. Over 40 single- and double-site viable mutants of bacteriophage IKe were isolated. Every residue in the TM segment, except the highly conserved Trp29, could be mutated to at least one other residue; polar and charged mutations occurred in the TM segment adjacent to the N-terminal domain (residues 24-28), while non-polar substitutions predominated in the C-terminal portion (residues 30-42). The Pro30 locus tolerated four mutations-Ala, Gly, Cys, and Ser which represent the four side chains of least volume. Mutant coat proteins obtained directly from the phage in milligram quantities were studied by circular dichroism spectroscopy and SDS-PAGE gels. Wild type IKe coat protein solubilized in sodium deoxycholate micelles was found to occur as an alpha-helical, monomeric species which is stable at 95 degrees C, whereas the mutant Pro30-->Gly undergoes an irreversible conformational transition at ca. 90 degrees C to an aggregated beta-sheet structure. The result that Pro30 stabilizes the TM helix in the micellar membrane suggests a sterically-restricted location for the wild type Pro pyrrolidine side chain in the bulky Trp-Pro-Val triad, where it may be positioned to direct the initiation of the subsequent TM core domain helix. PMID- 8216280 TI - Polymorphisms of the D4 dopamine receptor alleles in chronic alcoholism. AB - We have screened genomic DNA for the identification of D4 dopamine receptor polymorphisms. We show that the D4 dopamine receptor genotype in 72 severely affected chronic alcoholics is heterogeneous, with individuals homozygous and heterozygous for the various D4 receptor alleles. Alcoholics demonstrated a greater prevalence of the D4(3) (p < 0.005) and D4(6) (p < 0.005) alleles than has been reported in normals. There was a high prevalence of nicotine abuse among all D4 genotypes. The frequency of other drug abuse was higher in the D4(3,3) and the D4(4,7) groups, and the family history was strongly positive in the D4(2,4) group. The distribution of the D2 alleles showed equivalence in all D4 genotypes, except in D4(4,6) and D4(4,7) in whom the prevalence of the D2 A1A2 allele was 2 fold higher. The polymorphic variations of the D4 receptor genes should be among the factors considered in the assessment of individual differences in susceptibility to disorders such as alcohol abuse or drug addiction that may be mediated through central dopaminergic systems. PMID- 8216281 TI - Phosphorylation of a 62 kd porcine alpha-internexin, a newly identified intermediate filament protein. AB - A 62 kd protein was purified from the Triton-insoluble fraction of porcine brain white matter. This protein formed 10nm filaments, in vitro. The phosphorylation of the 62 kd protein by cAMP-dependent protein kinase caused electrophoretic mobility to shift to 66 kd on SDS-PAGE and a complete loss of the filament forming ability ensued. Amino acid sequences of four peptide fragments obtained from the 62 kd protein by lysylendopeptidase were identical with that of a 66 kd rat brain alpha-internexin. Amino acid analyses of the phosphopeptide fragment derived from phosphorylated porcine alpha-internexin revealed that the phosphorylation sites by cAMP-dependent protein kinase located in the amino terminal head domain of this protein. These results strongly suggest that alpha internexin polymerizes into 10nm filaments in vitro and that phosphorylation of the amino-terminal domain of alpha-internexin controls its polymerizability. PMID- 8216282 TI - Inhibition kinetics of chloramphenicol acetyltransferase by selected detergents. AB - Kinetic analyses indicate that the inhibitory effects of the nonionic detergents Triton X-100 and Nonidet P-40 on chloramphenicol acetyltransferase are exerted by a competitive and a non-competitive mechanism with respect to the substrates chloramphenicol and acetyl-CoA, respectively. Comparison with nonionic detergents without an aromatic moiety like that present in Triton X-100 and Nonidet P-40 suggests that the aromatic groups in these two detergents may compete with chloramphenicol for binding to the hydrophobic, active site in the chloramphenicol acetyltransferase. PMID- 8216283 TI - Cloning, expression and mutational analysis of SH-PTP2, human protein-tyrosine phosphatase. AB - A human cDNA clone encoding a nonreceptor protein-tyrosine-phosphatase (PTP) has been isolated and sequenced. The 2.1 kilobase pair cDNA encodes for a 593 amino acid protein that contains a single tyrosine phosphatase catalytic domain at the C-terminus. At the N-terminus the protein has two adjacent copies of Src homology region (SH2 domain) which show 61% and 73% identity at the amino acid level to the SH2 domains of the human PTP1C and Drosophila corkscrew protein, respectively. The overall homology between SH-PTP2 and PTP1C or to corkscrew protein is 58%. When this protein (or its catalytic domain) was expressed in E. coli as a glutathione-S-transferase fusion protein tyrosine-phosphatase activity was detected in bacterial cell extracts. Site-directed mutation made at the conserved cysteine (459) residue to serine within the highly conserved VHCXAGXXR sequence in the PTP catalytic domain resulted in complete loss of enzymatic activity demonstrating the importance of this cysteine residue in catalysis. Northern blot analysis showed that SH-PTP2 is expressed as a 6.5 kilobase mRNA in a number of fetal and adult human tissues and cell lines. The highest levels of its mRNA were detected in fetal brain and in adult heart tissue. The identification of SH-PTP2 along with PTP1C and corkscrew protein suggest that there exist a family of nonreceptor PTP containing SH2-domain which will participate in specific signal transduction pathways involving tyrosine phosphorylation-dephosphorylation. PMID- 8216284 TI - A novel peptide from funnel web spider venom, omega-Aga-TK, selectively blocks, P type calcium channels. AB - In the course of purification of omega-Aga-IVA, a specific P-type calcium channel blocker, from the venom of Agelenopsis aperta we discovered a novel peptide. This peptide, named omega-agatoxin Tsukuba (omega-Aga-TK), also blocked P-type channels and was twelve times more abundant in the venom than omega-Aga-IVA. omega-Aga-TK was purified to homogeneity by a two-step reverse-phase HPLC procedure. Its amino acid sequence is 71% identical to that of omega-Aga-IVA. omega-Aga-TK has a negatively charged N-terminus, whereas omega-Aga-IVA has a positively charged one. Electrophysiological data indicate that omega-Aga-TK is a potent and selective inhibitor of P-type channels. PMID- 8216285 TI - Cloning and functional expression of a human glucagon-like peptide-1 receptor. AB - A human glucagon-like 1 peptide receptor has been cloned from the gastric tumor cell line HGT-1. The cDNA clone encodes a protein of 463 amino acids and is a member of the superfamily of seven transmembrane domain G protein coupled receptors. Transfection of the human GLP-1 receptor into COS-7 cells confers upon them high affinity binding for [125I] GLP-1 (7-36) amide. In membranes prepared from COS-7 cells transfected with the human GLP-1 receptor, the binding of [125I] GLP-1 (7-36) amide is inhibited with the rank order of potency GLP-1 (7-36) amide > glucagon > secretin, characteristic of a GLP-1 receptor. The human GLP-1 receptor is functionally coupled to increases in intracellular cAMP in these cells: incubation of COS-7 cells expressing the human GLP-1 receptor with GLP-1 (7-36) amide gives rise to a 4-fold increase in cyclic AMP over basal levels, with an EC50 of 25pM. Glucagon is also a full agonist but is 200-fold less potent than GLP-1 (7-36) amide in stimulating the human GLP-1 receptor. PMID- 8216286 TI - Redistribution of 5-lipoxygenase and cytosolic phospholipase A2 to the nuclear fraction upon macrophage activation. AB - Both the cytosolic phospholipase A2 and 5-lipoxygenase enzymes redistribute from the high-speed supernatant to a particulate fraction upon cell activation with associated leukotriene synthesis, but the subcellular site to which these enzymes translocate is not known. In this study, we disrupted resting and ionophore A23187-stimulated rat peritoneal macrophages by N2 cavitation and separated lysates into nuclear, cytosolic, and crude membrane fractions; these were then examined by immunoblot analysis for their contents of immunoreactive cytosolic phospholipase A2, 5-lipoxygenase, and 5-lipoxygenase activating protein. 5 Lipoxygenase activating protein was localized predominantly in the nuclear fraction of both resting and activated cells, while both cytosolic phospholipase A2 and 5-lipoxygenase redistributed from the cytosol fraction in resting cells to the nuclear fraction in activated cells. These data demonstrate for the first time coordinate subcellular localization of the key proteins involved in leukotriene synthesis from endogenous arachidonate. PMID- 8216287 TI - Niemann-Pick C disease: cystine and lipids accumulate in the murine model of this lysosomal cholesterol lipidosis. AB - Cystine levels in tissues of the murine BALB/C mouse model of type C Niemann-Pick disease were shown to be greatly elevated. Subcellular fractionation of liver homogenates by differential centrifugation suggested preferential accumulation in a fraction corresponding to lysosomes. Developmentally, a sharp increase in the accumulation of cystine in the mutant mouse liver occurs subsequent to a similar change in the accumulation of cholesterol, sphingomyelin and glucocerebroside. The lysosomal accumulation of cystine in this mutant mouse provides the experimental opportunity to study some aspects of the deficiency of lysosomal cystine transport noted in cystinosis. PMID- 8216288 TI - Overexpression of p59-HBI (FKBP59), full length and domains, and characterization of PPlase activity. AB - It has been previously proposed that the rabbit p59-HBI (Heat shock protein Binding Immunophilin) or rFKBP59 (FK506 Binding Protein), found associated with the 90 kDa heat shock protein in nontransformed steroid receptor complexes, has three domains structurally related to hFKBP12 (Callebaut, I., Renoir, J.M., Lebeau, M.C., Massol, N., Burny, A., Baulieu, E.E. and Mornon, J.P. (1992) Proc. Natl. Acad. Sci., USA 89, 6270-6274). Here we report the overexpression, as fusion proteins in E. coli, of the full length p59-HBI and a series of p59-HBI mutants delimiting these domains and their respective peptidyl prolyl cis trans isomerase (PPlase) activity. The PPlase activity of p59-HBI is comparable to that of hFKBP12 and is due to domain p59-HBI I which displays the highest homology with this immunophilin. The residual enzymatic activity found in domain p59-HBI II is discussed. PMID- 8216289 TI - Threonine on amino acid position 868 in the human androgen receptor is essential for androgen binding specificity and functional activity. AB - The human androgen receptor gene in the androgen sensitive prostate tumor cell line (LNCaP) contains a point mutation in codon 868 resulting in the substitution of threonine by alanine. This amino acid change is responsible for the increased affinity of the mutant receptor protein for progestagens and estrogens. To further elucidate the role of threonine 868 on androgen binding capacity, specificity and functional activity, threonine 868 was substituted by six different amino acid residues. Substitution by aspartic acid, lysine or tyrosine totally eliminated androgen binding and the mutated androgen receptors did not have any transcriptional activating potential with either R1881, R5020 or estradiol. Introduction of a serine or an alanine broadened the steroid specificity, as did the introduction of a cysteine to a lesser degree. It is concluded that threonine on position 868 of the human androgen receptor limits the ligand specificity of the receptor to androgens. PMID- 8216290 TI - Specific uptake of succinylated proteins via a scavenger receptor-mediated mechanism in cultured brain microvessel endothelial cells. AB - Cellular uptake of succinylated catalase (Suc-CAT; Mw 227 kDa), bovine serum albumin (Suc-BSA; Mw 70 kDa), superoxide dismutase (Suc-SOD; Mw 34 kDa) and soybean trypsin inhibitor (Suc-STI; Mw 21 kDa) was studied using primary cultures of bovine brain microvessel endothelial cells (BMECs) developed as an in vitro model of the blood-brain barrier. Large succinylated proteins (Suc-CAT, Suc-BSA) were taken up by BMECs whereas significant uptake was not observed for native proteins and small succinylated proteins (Suc-SOD, Suc-STI). Uptake of Suc-BSA was significantly inhibited at 4 degrees C and in the presence of endocytosis inhibitors. Large succinylated proteins, maleylated BSA and dextran sulfate also showed competitive inhibition against Suc-BSA uptake while small succinylated proteins and carboxymethyl dextran did not show any effect. These results indicate that microvessel endothelial cells obtained from the brain endocytose succinylated proteins via a scavenger receptor-mediated mechanism for polyanions, and in addition, the importance of molecular weight or total numbers of anionic charges per one molecule of proteins is suggested. Usefulness of direct succinylation of proteins for their delivery to the brain capillary endothelium is thus demonstrated. PMID- 8216291 TI - Effect of aging on EGF stimulated DNA synthesis and EGF receptor levels in primary cultured rat hepatocytes. AB - Epidermal growth factor (EGF) stimulated DNA synthesis and EGF receptor levels were examined in primary cultured hepatocytes from 6, 12 and 24 month old rats. EGF stimulated DNA synthesis began after 12h and reached a peak at 48 h. Although no age difference was seen in the time course of DNA synthesis, the magnitude of synthesis at the peak time in 12 and 24 month old rat hepatocytes was reduced approximately 50 and 70%, as compared to that at 6 months. Hepatocyte EGF receptors exhibited no age difference in the equilibrium dissociation constant (Kd) or the density (Bmax). These results indicate that EGF stimulated DNA synthesis in rat hepatocytes declines with age, and that this reduction is not due to decreased receptor density or specific binding affinity. PMID- 8216292 TI - Thyrotropin, like luteinizing hormone (LH) and chorionic gonadotropin (CG), increases cAMP and inositol phosphate levels in cells with recombinant human LH/CG receptor. AB - Glycoprotein hormones and their receptors are each structurally related; thus, ligand-receptor cross reactivity may exist in pathologic situations, i.e., high human chorionic gonadotropin (hCG) levels in patients has been suggested to activate the thyrotropin receptor (TSHR). Studies with Cos-7 cells transfected with human CG and TSH receptor cDNAs suggest the converse may be more likely. Thus, in cells with TSHR, about 3 x 10(-11) and 3 x 10(-10) M TSH cause half maximal increases in cAMP and inositol phosphate (IP) levels, respectively, whereas 10(-6) M hCG has no effect on either. In cells with CGR, about 10(-11) and 10(-9) M CG or lutropin (LH) significantly increase cAMP and IP levels. Surprisingly, however, 10(-11) and 10(-9) M TSH are similarly effective in the two assays, respectively, and TSH increases cAMP and IP levels to the same extent as CG and LH. LH contamination of TSH is unlikely given similar results with highly purified TSH preparations from different sources, including recombinant TSH, and the specificity of simultaneously measured binding data. Thus, TSH binds with high affinity (Kd = 7 x 10(-11) M) to the human TSHR; hCG (up to 10(-7) M) does not displace TSH binding. Similarly, hCG binds with high affinity (Kd = 5 x 10(-10) M) to the hCGR and TSH is only a weak inhibitor (Ki = 1 x 10(-8) M). Stimulating TSHR autoantibodies, with no epitopes on the CGR, do not duplicate TSH action. The unusual agonist action of TSH with recombinant CGR is consistent with TSHR models describing separate agonist and antagonist determinants; it may be a factor in the precocious puberty of juvenile hypothyroidism with high TSH levels PMID- 8216293 TI - Purification and characterization of a 38-kDa protein, sp38, with zona pellucida binding property from porcine epididymal sperm. AB - A 38-kDa protein, sp38, was purified from the detergent extract of porcine epididymal sperm. Sp38 showed zona pellucida-binding properties similar to those of proacrosin. These two proteins specifically bound to the 90-kDa glycoprotein form of the zona pellucida components in a calcium-dependent manner. The binding of sp38 to the zona pellucida glycoprotein was inhibited by proacrosin. These findings suggest that the two proteins competitively interact with the zona pellucida during the early stage of fertilization. PMID- 8216294 TI - ETA and ETB receptors coexist on rabbit pulmonary artery vascular smooth muscle mediating contraction. AB - The possibility that both ETA and ETB endothelin receptor subtypes could mediate contractile activity in the same tissue was investigated in isolated, endothelium denuded rabbit pulmonary arteries. The ETB selective agonist, sarafotoxin 6c (S6c), produced potent contractile activity, equal to the non-selective ETA and ETB receptor agonist endothelin-1 (ET-1), indicating a contractile role for ETB receptors in this tissue. In addition BQ-123 (10.0 microM), the ETA selective antagonist, was only partially effective in blocking ET-1 induced contractions further indicating a contractile role for ETB receptors. However, the partial blockade by BQ-123 suggested a possible contractile role for ETA receptors. To address this possibility, ETB receptors were desensitized with a 30 minute pretreatment of S6c (0.01 microM). Under these conditions, we were able to demonstrate full ET-1 contractile activity that was now sensitive to blockade by BQ-123. The coexistence of both ETA and ETB receptors was confirmed through receptor binding experiments indicating 40/60 ratio, respectively. We conclude that 1) both ETA and ETB receptors coexist on vascular smooth muscle of rabbit pulmonary artery, 2) activation of either receptors subtype results in contraction, and 3) prolong activation of the ETB receptor subtype produces tachyphylaxis preventing further activation by S6c or ET-1. PMID- 8216295 TI - Anti-phosphoserine and anti-phosphothreonine antibodies modulate autophosphorylation of the insulin receptor but not EGF receptor. AB - We examined the effect of anti-phosphothreonine and anti-phosphoserine antibodies on insulin receptor autophosphorylation. These antibodies did not affect insulin binding activity of the receptor. These antibodies, however, inhibited insulin stimulated autophosphorylation of insulin receptor, while did not affect EGF stimulated autophosphorylation of EGF receptor. The inhibition was reversed by adding large amounts of phosphoserine or phosphothreonine. These data suggest that phosphoserine and phosphothreonine on insulin receptor play an important role in insulin-induced conformational change of the receptor. PMID- 8216296 TI - The bcl-2 protein is inserted into the outer membrane but not into the inner membrane of rat liver mitochondria in vitro. AB - The bcl-2 gene encodes a 26 kDa protein, overexpression of which blocks cell apoptosis. Since conflicting data have been reported concerning the localization of the Bcl-2 protein with mitochondrial inner and outer membranes, we analyzed in vitro import of the human Bcl-2 protein into isolated rat liver mitochondria. The Bcl-2 protein translated in rabbit reticulocyte lysate was efficiently inserted into the mitochondrial outer rather than the inner membrane in a membrane potential-independent manner. The carboxyl-terminal hydrophobic stretch is essential for the Bcl-2 protein to integrate into the outer membrane. Binding of the Bcl-2 protein to the mitochondria was not affected by pretreatment of the mitochondria with trypsin, indicating that the Bcl-2 protein does not require protease-sensitive mitochondrial surface components for its membrane insertion. PMID- 8216297 TI - Identification of amyloid precursor protein in synaptic plasma membrane. AB - Although the etiology of Alzheimer's disease has not been elucidated yet, dysfunction and loss of synapses are believed to cause dementia. Recent studies suggest that the primary cause of the disease is closely related to the aberrant processing of the amyloid precursor protein (APP). To investigate the localization of APP at synaptic sites, we obtained synaptic plasma membrane and synaptic vesicles from rat brain. Enhanced chemiluminescence (ECL) western blot analysis using two specific polyclonal antibodies against APP revealed strong APP immunoreactivity in the synaptic plasma membrane, but not in the synaptic vesicle fraction. These data indicate that APP is localized at the synaptic plasma membrane and may play a role in physiological synaptic activity. Alternative localization or aberrant processing of APP at the synaptic site may cause impairment of synaptic function in Alzheimer's disease. PMID- 8216298 TI - Vasodilator effect of adrenomedullin and calcitonin gene-related peptide receptors in rat mesenteric vascular beds. AB - The effect of adrenomedullin, a novel peptide of 52 amino acids, on vascular tone was investigated in the perfused rat mesenteric vascular bed. In the vasculature contracted with methoxamine, perfusion of adrenomedullin (10(-11)-10(-7) M) caused a concentration-dependent decrease in perfusion pressure due to vasodilation. Additionally, a bolus infusion of adrenomedullin (300 and 500 pmol) produced a long-lasting vasodilator response, which was not affected in the presence of atropine (10(-7) M) and propranolol (10(-7) M). However, this response was inhibited in the presence of CGRP [8-37] (10(-6) M), an antagonist for CGRP receptor. These results suggest that adrenomedullin induces nonadrenergic and noncholinergic vasodilation in which CGRP receptors may be involved. PMID- 8216299 TI - Growth factor mRNA profiles in unstimulated human mononuclear cells: identification of genes which are constitutively and variably expressed. AB - Quiescent human mononuclear cells (MNC) as studied ex vivo express highly specific mRNA patterns of growth factors: We recently demonstrated that unstimulated MNC constitutively express the genes for the A and B chains of platelet-derived growth factor (PDGF). This expression was down-regulated by dietary omega-3 fatty acids. We now report that unstimulated human MNC express the genes for platelet-derived endothelial cell growth factor (PD-ECGF), insulin like growth factor (IGF-1A, -1B) and transforming growth factor-beta 1 (TGF-beta 1). In contrast, acidic and basic fibroblast GF (FGFs), insulin-like GF-2 (IGF 2), transforming GF-alpha (TGF-alpha) and epidermal GF (EGF) were not expressed in MNC, nor were alpha- and beta- receptors for PDGF. Quantitatively, as measured over a period of six weeks, expression of PD-ECGF was constant, whereas TGF-beta 1, IGF-1A, and IGF-1B were expressed at varying levels and all independently of each other. Dietary omega-3 fatty acids had no effect on gene expression. Our results also indicate that down-regulation of PDGF gene expression represents a specific and possibly therapeutic effect of dietary fish oil supplementation. PMID- 8216300 TI - Effects of synthetic retinoids and retinoic acid isomers on the expression of alkaline phosphatase in F9 teratocarcinoma cells. AB - Expression of ALP in F9 teratocarcinoma cells is induced by all-trans retinoic acid (ATRA) (Gianni' et al., Biochem. J. 274: 673-678, 1991). The specific ligand for retinoic acid related receptors (RXRs), 9-cis retinoic acid (9-cis RA), and three synthetic analogs binding to the alpha, beta and gamma forms of the retinoic acid receptors (RARs), AM580, CD2019, and CD437, were used to study their effects on alkaline phosphatase (ALP) enzymatic activity and mRNA levels. At concentrations close to the Kd for their respective receptors, 9-cis RA, AM580 (the RAR alpha agonist) and CD437 (the RAR gamma agonist) clearly upregulate the expression of the ALP gene, whereas the effect of CD2019 (the RAR beta agonist) is very modest. A specific inhibitor of the RAR alpha, Ro 41-5253, completely blocks the induction of ALP triggered by AM580, while it has minor effects on the upregulation caused by ATRA, 9-cis RA, CD437 and CD2019. The induction of ALP observed with the various retinoids is inhibited by the contemporaneous treatment with dibutyryl cAMP. The levels of the RAR alpha and gamma transcripts are unaltered, while RAR beta mRNAs are induced by ATRA, AM580, CD437 and to a lower extent by 9-cis RA and CD2019. PMID- 8216301 TI - On the accurate determination of serotonin in human plasma. AB - Serotonin (5-hydroxytryptamine, 5-HT) in blood is stored in platelets and has vascular and platelet stimulating effects when released into plasma. Accurate measurements of 5-HT in plasma are complicated by inadvertent platelet activation causing sampling artifacts and by analytical problems when determining trace levels. We developed an assay for plasma 5-HT based on solid-phase extraction (Sep-Pak C18), aqueous acetylation, pentafluoropropionylation, and negative ion chemical ionization gas chromatography-mass spectrometry. The method was able to recover 5-HT from plasma by > 90% and to quantitate with a precision of 7.5% at a level of 0.5 nmol/l. It was used to define blood sampling and sample handling procedures giving low and consistent values for 5-HT. A good blood sampling technique, adequate platelet stabilization in the test tube, and rapid high speed centrifugation of the blood resulted in low plasma levels of both 5-HT and beta thromboglobulin (a platelet release product). Using these procedures plasma 5-HT levels in healthy volunteers were found to be 0.77 +/- 0.38 (mean +/- S.D.; range 0.27-1.49) nmol/l (n = 18), which is 4-100-fold lower than previously reported values. PMID- 8216302 TI - Cellular cyclic AMP levels modulate insulin sensitivity and responsiveness- evidence against a significant role of Gi in insulin signal transduction. AB - Treating rats with pertussis toxin (PTX) both elevated the adipocyte cAMP levels and impaired sensitivity and responsiveness to the antilipolytic effect of insulin in the presence of different beta-adrenergic agonists. However, in the presence of a fixed medium concentration of the degradable cAMP analogue, 8-bromo cAMP, the effect of insulin was similar in PTX- and control cells. Elevating the cAMP levels in control cells either through different concentrations of the cAMP analogue or addition of adenosine deaminase impaired both insulin sensitivity and responsiveness to a similar extent as that seen in PTX-treated cells. The antilipolytic effect of insulin was exerted through the activation of the cGMP inhibitable phosphodiesterase (cGI-PDE) as it was dose-dependently impaired by the specific cGI-PDE inhibitor OPC 3911. The results show the importance of the cellular cAMP levels in modulating insulin sensitivity and action. Gi plays a minor role, if any, for the signal transduction of the antilipolytic effect of insulin. PMID- 8216303 TI - Phosphorylation of half and all sites in H+,K(+)-ATPase results in opposite changes in tryptophan fluorescence. AB - The Trp fluorescence increased accompanying phosphorylation by ATP and Acetyl phosphate (AcP) in pig stomach H+,K(+)-ATPase, respectively, to maximum values of 0.86 and 0.37%. The stoichiometry of the maximum amount of phosphoenzyme formed from ATP, that from AcP, that from inorganic phosphate (Pi), and the maximum amount of ATP binding to the enzyme was shown to be close to 1:2:2:2. Phosphoenzymes formed were shown to be turning over. The addition of K+ reduced the amount of phosphoenzyme from ATP to one-tenth but reduced those from AcP or Pi to only the half. The data show that the Trp fluorescence increased with phosphorylation of half of the sites but decreased with phosphorylation of all sites. PMID- 8216304 TI - The stimulation of pp42mapkinase by insulin does not correlate with its metabolic actions in cells overexpressing mutant insulin receptors. AB - Naturally occurring human insulin receptor mutants Ser1200 and Thr1134, and a site-directed mutant Arg1030 overexpressed in Chinese hamster ovary (CHO) cells, bind insulin with affinities identical to wildtype receptors but are apparently kinase deficient. Cells expressing the Ser1200 receptor exhibit insulin stimulation of glycogen synthesis similar to these bearing the wildtype receptor, but fail to mediate insulin-responsive DNA synthesis. In contrast, the Thr1134 and Arg1030 mutants exhibit no response to insulin. The activity of Mitogen Activated Protein (MAP) kinase in cells transfected with wildtype receptor is more responsive to insulin than that detected in untransfected parental cells, while cells bearing any of the mutant receptors are less responsive than the parental cells. These differences in the stimulation of MAP kinase activity are paralleled by differences in insulin-dependent phosphorylation of the enzyme. These results suggest that the p42 MAP kinase is not universally required for the metabolic effects of insulin. PMID- 8216305 TI - Mouse relaxin: synthesis and biological activity of the first relaxin with an unusual crosslinking pattern. AB - According to a recently published cDNA sequence, mouse relaxin has an extra amino acid in the C-terminal end of the A chain and thus an interchain loop consisting of 25 amino acids instead of the usual 24-membered ring. Because of the restrictive disulfide link arrangement the extra residue can be expected to cause a loop out in the C-terminal alpha-helix. We have chemically synthesized authentic mouse relaxin as well as an analog without the additional A chain residue and found that the native hormone, although active, was inferior to its insulin-like analog. This result is in harmony with our previous study which suggests that the surface of relaxin represented by the C-terminal helix of the A chain is positioned opposite to the surface that contains the receptor interaction site and therefore is less sensitive to modifications. PMID- 8216306 TI - BQ-123 identifies heterogeneity and allosteric interactions at the rat heart endothelin receptor. AB - Studies of the binding of endothelin-1 (ET-1) to its receptors in the rat heart, as well as kinetic measurements in the presence and absence of the specific antagonist BQ-123, appear to exclude a scheme of simple competitive inhibition and an interaction of ET-1 with a homogeneous population of receptors. Studies with BQ-123 established the presence of three subtypes of endothelin receptors and an allosteric interaction, suggesting the possible existence of a specific site for BQ-123 that interacts and/or interferes with the properties of endothelin-binding sites. PMID- 8216307 TI - v-Src-induced transformation is inhibited by okadaic acid. AB - The tumor promoter okadaic acid is a potent inhibitor of the serine/threonine protein phosphatases 1 and 2A. Addition of okadaic acid to v-Src-transformed BALB/c 3T3 cells reverted them to a flat morphology, increased fibronectin levels in the extracellular matrix, reduced saturation density, and inhibited the formation of colonies in soft agar. The ability of v-Src-transformed cells to proliferate in low serum was also inhibited by okadaic acid. These data implicate serine/threonine phosphatases in v-Src-induced transformation. PMID- 8216308 TI - An antisense oligodeoxynucleotide approach to investigate the function of the nuclear-encoded subunits of human cytochrome c oxidase. AB - On treatment of human liver Hep G2 cells with thiamphenicol, intramitochondrial levels of cytochrome c oxidase (COX) nuclear gene products were shown to decrease in tandem with the mitochondrially-encoded subunits except, however, for subunit IV which proved to be remarkably stable. This nonspecific decrease in subunit level was utilized to assess the function of subunit VIIa-L. Thiamphenicol pretreated cells were bathed in anti-VIIa-L oligonucleotides and the recovery rate of COX activity compared to control oligomer-untreated cells or cells with a similar concentration of a randomized oligomer. No difference in recovery rate was noted for the first two days post oligomer addition, after which a sharp decrease in recovery was noted for the anti-VIIa-L treated cells only. We conclude: (i) subunit IV is stable in the absence of other COX components, (ii) subunit VIIa-L is required for maintaining normal levels of COX activity, (iii) an antisense oligodeoxynucleotide approach for assessing the function of COX nuclear gene products is made feasible by first reducing levels of the complex and then assaying its recovery rate in the presence of transcript-specific antisense oligonucleotides. PMID- 8216309 TI - Novel regulatory sites of the human heme oxygenase-1 promoter region. AB - Heme oxygenase is the rate-limiting enzyme in heme catabolism, the activity of which is induced by several agents including its substrate heme, u.v. radiation and other oxidant injurious conditions. Its biological function is to provide a specific regulatory mechanism for control of the level of many heme proteins. Using a computer-assisted approach, we examined the presence of different regulatory elements on the human heme oxygenase-1 promoter region which could possibly be involved in its regulation. We identified several NFkB and AP-2-like binding sites in the 5' untranslated region of the human heme oxygenase gene. DNase I footprint analysis confirmed the presence of these two important transcriptional sites. This study is the first to reveal the presence of NFkB and AP-2 binding sites in the heme oxygenase-1 promoter region and thus suggests a role for these transcriptional factors in the regulation of heme oxygenase-1 expression, a stress and heat shock protein, under injury conditions. PMID- 8216310 TI - Parallel induction of nitric oxide and glucose-6-phosphate dehydrogenase in activated bone marrow derived macrophages. AB - The production of nitric oxide (NO.) and the induction of glucose-6-phosphate dehydrogenase by lipopolysaccharides (LPS) from different sources was studied in bone marrow derived macrophages (BMM phi). NO. production was found to be linked to the induction of glucose-6-phosphate dehydrogenase, suggesting the possible involvement of this enzyme in the cytotoxic mechanism resulting from the release of NO. by activated macrophages. PMID- 8216311 TI - Use of thiocyanate ion as a mediator ligand in connecting acidic and alkaline forms of ferric myoglobin via paramagnetic 1H-NMR saturation transfer. AB - Paramagnetic 1H-NMR saturation transfer experiments have been used successfully to connect acidic and alkaline forms of equine ferric myoglobin through met thiocyanate form as a mediator. The saturation transfer connectivities have provided the first assignments of the heme methyl proton resonances of equine met hydroxyl myoglobin. Without mediator ligand, the acid-alkaline transition in this myoglobin is not accessible to the present technique due to the rapid exchange process between the two forms. Analysis of the intrinsic spin-lattice relaxation time and saturation transfer factor provided the life-time of met-thiocyanate and equine met-hydroxyl myoglobins under the experimental conditions used. PMID- 8216312 TI - Biochemical consequences of a large deletion in the mitochondrial genome of a Drosophila subobscura strain. AB - A mutant strain of D. Subobscura possesses two populations of mitochondrial genomes: a population identical to that of the wild strain (20%) and a dominant population (80%) which has lost more than 30% of its coding zone by deletion. Spectrophotometric determination of respiratory complex activities shows that: complex I (5 genes implicated in deletion) presents maximal activity reduced by 40%, whereas that of complex III (concerned by cytochrome b) is lowered by 30%. Nevertheless, polarographic determinations of substrate oxidation show activity of complex I to be reduced by 30%. In contrast, complex III activity is similar to that measured in the wild strain. The predominant use of one part of the respiratory chain may account for the fact that the mutant strain is apparently unaffected by mutation. PMID- 8216313 TI - Mammalian cochlear outer hair cells density evaluated by means of an optical tweezer. AB - We report on the first individual measurements of guinea pig's cochlear outer hair cells densities. Cells were isolated in vitro and manipulated with an optical tweezer. They were levitated in an upward laser beam coaxially trapping the cells. Then they were released by switching off the laser and let fall down in upright position. Measuring their speed and using the Stokes' law, we calculated their mean density. In our experimental frame, the results suggest that the density of the cellular body (between the basal nucleus and the apical cuticular plate) remains quasi constant whatever the cells' length. This implies that density variation of the cellular body does not participate in an intrinsic tuning mechanism. PMID- 8216314 TI - Endothelin-3 mediated proliferation in wounded human umbilical vein endothelial cells. AB - An in vitro model of endothelial cell injury was used to investigate the role of endothelins and related peptides in endothelial repair. Endothelin-3 (10-100 nM) enhanced wound repair over an 18 h period by promoting proliferation, an effect not inhibited by the specific ETA receptor antagonist BQ-123 (100 nM) or the mixed ETA/ETB antagonist PD142893 (10 microM). Like endothelin-3, the ETB selective agonists [Ala1,3,11,15]endothelin-1 and sarafotoxin S6c were able to enhance wound repair over the same dose range. Neither endothelin-1 nor endothelin-2, however, had any effect on endothelial cell wound healing. Inhibition of cyclo-oxygenase or neutralisation of basic fibroblast growth factor did not inhibit this endothelin-3-mediated event. These results suggest that endothelin-3 might have a direct role in endothelial cell proliferation as a response to injury which is not mediated by either of the currently defined ETA and ETB receptors. PMID- 8216315 TI - Efficient lipofection of human trophoblast cells in primary cultures. AB - Human choriosomatomammotropic hormone, also known as placental lactogen, is expressed in syncytiotrophoblast cells of the placenta. Studying transcriptional regulation of the genes coding for this hormone, we became interested in transfecting primary cultures of these trophoblast cells. In this study, we show that it is possible to transfect, by the lipofection method, these giant cells in an efficient and reproducible manner. We show the presence of an enhancer region downstream from the hCS-B gene, functionally active in these cells; furthermore, we demonstrate the placenta-specific characteristic of this enhancer, previously identified in a human choriocarcinoma cell line. PMID- 8216316 TI - Metformin increases glucose transporter protein and gene expression in human fibroblasts. AB - To investigate the effect of the antihyperglycemic drug metformin on glucose transporter protein and gene expression, skin fibroblasts obtained from normal and diabetic volunteers were grown in culture and incubated with metformin at various concentration for up to 16 days. Metformin caused a dose and time dependent increase in GLUT1 number with a maximum at a concentration of 10 micrograms metformin given over 4 days. This was accompanied by an increase in GLUT1 mRNA, suggesting that metformin has a stimulating effect on glucose transporter gene expression. No significant difference was observed between cells obtained from type II diabetic patients and those from controls. We conclude that in human fibroblasts GLUT1 de novo synthesis is involved in the long term effect of metformin on glucose transport. PMID- 8216317 TI - Local regulatory effects of activin A and follistatin on meiotic maturation of rat oocytes. AB - Activin A and follistatin identified in follicular fluids have been shown to regulate follicular development. Activin A, in a dose responsive manner, increased the percentage of germinal vesicle breakdown that served as a marker for the resumption of meiosis of oocytes in vitro, especially these obtained from immature follicles. This effect of activin A was inhibited by the activin-binding protein, follistatin. Follistatin alone exerted an inhibitory effect on oocyte maturation. Reverse transcription and polymerase chain reaction revealed the expression of activin beta A and activin type IIA receptor gene transcripts in the oocytes. Activin A, along with follistatin, appears to play a local regulatory role in the meiotic maturation of rat oocytes. PMID- 8216318 TI - Hypokalemia downregulates cardiac alpha 1 and skeletal muscle alpha 2 isoforms of Na+,K(+)-ATPase in ferrets. AB - K+ deficiency decreases amount of Na+,K(+)-ATPase in cardiac and skeletal muscle (SM) and differentially regulates alpha- and beta-subunit isoforms. Expression of the alpha 3 isoform during K+ deficiency is unknown, however. In the myocardium of normal adult ferrets, alpha 1 and alpha 3 isoforms are expressed. Therefore, we examined in ferrets the effects of K+ deficiency in levels of alpha- and beta subunit isoforms. A K+ deficient diet greatly reduced plasma K+ concentrations. Tissue K+ content in myocardium remained unchanged, whereas that of SM decreased markedly. Corresponding to these changes, Na+,K(+)-ATPase enzyme activity decreased in SM but not in heart. Levels of alpha 1 in heart and alpha 2 in SM decreased, whereas those of alpha 3 in heart and alpha 1 in SM remained unchanged; beta 1 remained unchanged in both tissues. Thus, in ferrets, K+ deficiency differentially regulated the levels of Na+,K(+)-ATPase isoforms in an isoform- and tissue-dependent manner. PMID- 8216319 TI - Brain-specific prostaglandin D2 synthetase mRNA is dependent on thyroid hormone during rat brain development. AB - We have previously described several cDNA clones whose expression is affected by thyroid hormone during rat brain development. We now report the identification of one of these, the E2 clone, as the brain-specific prostaglandin D2 (PGD2) synthetase gene. Sequence comparison shows a nearly complete identity between the 356 nucleotides of the E2 clone and nucleotides 403 to 759 of PGD2 synthetase cDNA. The pattern of E2 expression corresponds to that expected for brain specific PGD2 synthetase gene, i.e. the corresponding mRNA is not detected in any other tissue analyzed apart of the brain, and it was present at different levels in all brain regions. Hypothyroidism decreased E2 mRNA concentrations in cerebral cortex and cerebellum. Control of the level of expression of PGD2 synthetase gene may contribute the complex effects of thyroid hormone on brain development and function. PMID- 8216320 TI - Expression of the human follicle-stimulating hormone receptor in the baculovirus system. AB - Human follitropin receptor (hFSHR) cDNA was inserted into the genome of Autographa californica nuclear polyhedrosis virus under the control of the polyhedrin promoter. Spodoptera frugiperda (Sf9) insect cells expressed the hFSHR at the membrane level, 2-3 days after infection. Ligand binding analysis demonstrated saturable, high-affinity binding of 125I-labeled recombinant hFSH (Kd = 0.17 nM) as well as binding specificity for both human and equine FSH. Interestingly, a highly purified preparation of equine choriogonadotropin was found to compete with the binding of 125I-rhFSH. Finally, Western-blot analysis, using a monoclonal antipeptide antibody directed to the 178-206 region of the hFSHR, revealed two bands migrating at M(r) 77 and 130 kDa. PMID- 8216321 TI - Dermatofibrosarcoma protuberans: increased growth response to platelet-derived growth factor BB in cell culture. AB - Dermatofibrosarcoma protuberans (DFSP) is a malignant tumor originating in the dermis. Although it is locally aggressive and recurs unless completely excised, it only rarely metastasizes. In the present study, we established 4 cultured DFSP cell strains, which were almost identical to normal skin fibroblasts when observed under a phase-contrast-microscope, and we observed their responses to various growth factors. DFSP cells showed significantly greater response to platelet-derived growth factor BB(PDGF BB) and transforming growth factor beta 1(TGF beta 1) than normal fibroblasts. We also determined upregulation of PDGF beta receptors in DFSP cells by both 125I PDGF-BB binding assay and immunoblotting analysis. These findings suggest that the interaction between the PDGF-B chain and the overexpression of PDGF beta receptors might play a role in the development of DFSP tumors. PMID- 8216322 TI - Pseudomonas aeruginosa contains an IHF-like protein that binds to the algD promoter. AB - An IHF-like protein has been purified from a Pseudomonas aeruginosa strain isolated from a cystic fibrosis patient, by the rapid purification method described for the isolation of IHF from Rhodobacter capsulatus. The IHF of P. aeruginosa is an alpha beta heterodimer (subunits of 10 and 11 kDa) similar to IHF from Escherichia coli and from R. capsulatus; the N-terminal amino acid sequences of the isolated subunits share a high degree of identity with their homologs from E. coli. P. aeruginosa IHF is able to bind to the promoter of the hydrogenase structural genes (hupSL) of R. capsulatus as do the other two IHF proteins. It is also demonstrated by gel retardation assays that P. aeruginosa IHF forms a stable complex with the algD promoter in vitro, an indication that the protein is involved in the regulation of algD gene expression in P. aeruginosa. PMID- 8216323 TI - Purification and partial characterization of a N-glycolylneuraminic acid specific lectin from the clam Anadara granosa (L). AB - The N-glycolylneuraminic acid-specific lectin (AFL) from the foot muscles of the marine clam Anadara granosa has been purified to homogeneity by affinity chromatography on bovine submaxillary mucin-Sepharose 4B. The Ca(2+)-dependent lectin agglutinates rabbit erythrocytes. The purified lectin is a tetrameric protein of native M(r) 254 kDa having a pI value of 6.65. The M(r) of two subunits is 65 kDa each and that of the remaining two is 62 kDa each. The dominant amino acids of the lectin are aspartic acid, glutamic acid, serine and glycine. The lectin activity is inhibited only by N-glycolylneuraminic acid specially when it is present in the macromolecular structure of mucin viz., porcine submaxillary mucin, which is the most potent inhibitor. The binding site does not recognize N-acetylneuraminic acid. Due to this strict specificity, the lectin appears to be unique. PMID- 8216324 TI - Quantification of countercurrent distribution: from molecular partition to animal behavior. AB - Countercurrent distribution is a very effective method for separating a variety of substances including molecules, cells, and animals on the basis of partition between two solvent or behavioral phases. Distribution of a substance in this multi-cycle procedure can be described in terms of its partition coefficient (K) or the fraction of the substance that moves to the mobile phase in each cycle (p). It is currently difficult to calculate the value of p or K directly from an experimental distribution. Such direct calculation will simplify comparison of various experimental populations for the properties which determine their distribution, such as the surface properties of cells or behavioral preferences of animals. This report describes, and provides a theoretical basis for, an extremely simple method to calculate p or K directly from an experimental countercurrent distribution. PMID- 8216325 TI - Circular dichroism analysis of a synthetic peptide corresponding to the alpha, alpha-corner motif of hemoglobin. AB - The alpha, alpha-corner is a helix-turn-helix super-secondary structural protein motif where the two alpha-helices cross at approximately right angles. This motif has been observed in a wide variety of proteins and thus, has been proposed to be a protein folding initiator. We sought to test this hypothesis by synthesizing a peptide corresponding to the alpha, alpha-corner of the alpha-chain of horse methemoglobin (residues 80-108) and examining its structure by circular dichroism. We found that the alpha, alpha-corner peptide is moderately helical in water and fully helical in trifluoroethanol, as solvent that approximates the hydrophobic surroundings of the excised portion of the protein. The helicity of our synthetic peptide suggests that the alpha, alpha-corner may in fact have some stability on its own and thus, may be capable of initiating protein folding. PMID- 8216326 TI - Exon structure at the human ACP1 locus supports alternative splicing model for f and s isozyme generation. AB - The human ACP1 locus encodes a genetically polymorphic cytoplasmic low-molecular weight acid phosphatase. Each of the common alleles encodes two isoforms, f and s. Both isozymes are of equal length (157 residues) but differ in sequence over an internal 34 residue segment. Substantial portions of the ACP1*A, *B and *C alleles common to Europeans have been sequenced. Six linearly positioned exons containing codons 14 to 157 were identified. Two exons of equal length (114bp) interspaced by a short (41bp), probably nonfunctional, intron encode the specific f and s segments, respectively. These findings strongly support an alternative RNA splicing hypothesis. In addition, three allele-specific base substitutions were encountered. PMID- 8216327 TI - Acetylation of core histones causes the unfolding of 30 nm chromatin fiber: analysis by agarose gel electrophoresis. AB - In the present work it was directly demonstrated that increased acetylation level of histones causes the decompactization of 30 nm chromatin fiber, as revealed by low-percentage agarose gel electrophoresis. In the light of obtained results the possible molecular mechanism of the decompactization of acetylated fiber is discussed. PMID- 8216328 TI - Elevated intrinsic reactivity of seryl hydroxyl groups within the linear peptide triads His-Xaa-Ser or Ser-Xaa-His. AB - Chemical modification studies of peptide hormones and random peptides have revealed that seryl hydroxyl groups had enhanced reactivity toward acylating reagents when they occurred in the linear triads His-Xaa-Ser or Ser-Xaa-His (Xaa = any amino acid). O-acylation of serine within these triads was achieved by reaction with N-hydroxysuccinimide esters of biotin (NHS-biotin) and succinic anhydride. Seryl residues not occurring in His-Xaa-Ser/Ser-Xaa-His triads showed no reactivity towards NHS-biotin under reaction conditions described. Results of histidine replacement studies and studies of the pH dependence of O-biotinylation indicated that the increased nucleophilicity of the seryl hydroxyl group was due to intramolecular interaction between the seryl and histidyl residues. Our findings provide strong evidence that such triads represent novel consensus motifs in peptides. PMID- 8216329 TI - Molecular cloning of cDNA encoding human drebrin E and chromosomal mapping of its gene. AB - Drebrins are novel actin-binding proteins in the brain which are developmentally regulated. Three isoforms: two embryonic types (E1 and E2) and an adult type (A) are generated by alternative RNA splicing from a single debrin gene in the chicken brain. A full length cDNA clone of human drebrin E has been isolated from a cDNA library of human fetus brain. The clone is 2596 base pairs in length and contains an open reading frame of 1947 nucleotides encoding a protein of 649 amino acids. The deduced amino acid sequence, except for the internal 138 nucleotide sequence (ins2), exhibits 88% homology with rat drebrin A. Spot blot hybridization using flow-sorted human chromosomes provides evidence that the gene encoding human drebrin protein locates on human chromosome 5. PMID- 8216330 TI - An endoribonuclease activity associated with Lettre Ehrlich ascites tumor cell mitochondria. AB - The splicing of 3.36kb mouse mitochondrial mRNA precursor(L-strand) to 69bp RNA component is shown to be mediated by an endoribonuclease activity associated with Lettre Ehrlich ascites tumor cell mitochondria. The enzymic activity was partially purified by column chromatography and the in vitro reconstituted RNA processing assay was performed to document this finding. PMID- 8216331 TI - Purification and characterization of a catalytically active human liver UDP glucuronosyltransferase expressed as a fusion protein in E. coli. AB - The purification and the characterization of functional human liver UDP glucuronosyltransferase 2B4 produced as a Staphylococcus aureus protein A fusion protein in E. coli are described. The purified fusion protein was able to catalyze the glucuronidation of hyodeoxycholic acid, the major substrate described for this isoform to date. The effects of the amount and the nature of the phospholipids upon reconstitution into phospholipid micelles were investigated. Apparent determined Km values for hyodeoxycholic acid and UDP glucuronic acid were 0.55 and 0.43 mM, respectively. Moreover, photoaffinity labelling of the fusion protein with a photoactivatable analog of UDP-glucuronic acid strongly suggested that this recombinant protein exhibited similar binding properties as the microsomal protein, which emphasizes its use for further structural analyses. PMID- 8216332 TI - Growth inhibition of human keratinocytes by 1,25-dihydroxyvitamin D3 is linked to dephosphorylation of retinoblastoma gene product. AB - Human keratinocyte is one of the target cells for 1,25(OH)2D3, a biologically active form of vitamin D3. It induces the differentiation and growth inhibition of human keratinocytes. In order to understand the inhibitory mechanism of 1,25(OH)2D3, we examined its effect on cell cycle kinetics and retinoblastoma gene product (pRB), one of tumor suppressor gene products, in normal human keratinocytes. Cell cycle analysis demonstrated that 10(-6) M of 1,25(OH)2D3 induced cell cycle arrest in both G1/G0 (63.4% +/- 1.4 versus 52.7% +/- 1.2 in control, p < 0.05) and G2 + M (21.5% +/- 0.6 versus 10.9% +/- 0.8 in control, P < 0.05) phase. Addition of 10(-6) M of 1,25(OH)2D3 increased dephosphorylated pRB in a time dependent manner from 23% at 0 h to 58% at 48 h. Since the phosphorylation of pRB is supposed to be essential for the progression from G1 to S phase, the inhibition of pRB phosphorylation could be responsible for the G1/G0 growth arrest induced by 1,25(OH)2D3 in normal human keratinocytes. PMID- 8216333 TI - Nitric oxide-releasing agents enhance cytokine-induced tumor necrosis factor synthesis in human mononuclear cells. AB - In septic shock tumor necrosis factor (TNF) leads to increased nitric oxide (NO) production by induction of NO synthase. An inverse regulatory effect, the influence of NO on cytokine synthesis, has rarely been investigated. The present study assessed the influence of NO-releasing agents on TNF production from interleukin-1 alpha (IL-1 alpha)-stimulated human peripheral blood mononuclear cells (PBMC). 3-Morpholino-sydnonimine (SIN-1) enhanced IL-1 alpha-induced TNF synthesis to a maximum of 272% (mean of n = 5 donors), with 100% set as TNF production by stimulation with IL-1 alpha alone. This finding was confirmed using another NO-donor, i.e., sodium nitroprusside (SNP). The effect was specific for TNF compared to the uninfluenced synthesis of IL-1 beta. Kinetic analysis showed the most pronounced increase in TNF synthesis when SIN-1 was added during the first 60 min after IL-1 alpha addition. These data reveal an enhancing effect of NO on cytokine-induced TNF synthesis. It may contribute to the regulation of TNF synthesis in pathological processes such as microbicidal activity, tumor cell lysis or endothelium-mediated hypotension. PMID- 8216334 TI - Evidence of post-transcriptional regulation in mammalian mitochondrial biogenesis. AB - We have previously shown that the nuclear-encoded gene's expression of mitochondrial beta-subunit of the F1-ATPase complex in rat liver is regulated at the translational level (Luis, A.M., Izquierdo, J.M., Ostronoff, L.K., Santaren, J., Salinas, M., and Cuezva, J.M. (1993) J. Biol. Chem. 268, 1868-1875). In this paper we report that the different steady-state levels of ATP synthase beta subunit mRNA detected in rat tissues are not paralleled by a proportional content of immunodetectable beta-F1-ATPase protein. The results suggest that tissue specific transcriptional and post-transcriptional mechanisms contribute to differential mitochondrial biogenesis in mammalian cells. On the other hand, steady-state mRNA levels of the mitochondrial encoded ATP synthase subunits (ATP 6+8) indicate that nuclear and mitochondrial-encoded transcripts for this complex are in close relation, that is, the expression of both nuclear and mitochondrial genes is coordinated in all tissues examined. PMID- 8216335 TI - Characterization of the glycine-dependent redox-cycling activity in animal fluids and tissues using specific inhibitors and activators: evidence for presence of PQQ. AB - Pyrroloquinoline quinone, a redox cofactor first isolated from bacteria, efficiently catalyzes the nonenzymatic oxidation of glycine in the presence of nitroblue tetrazolium. We report that certain metallic cations and heterocyclic aromatic cations, like the N-methyl phenazonium cation and aryl-iodonium compounds, strongly and specifically inhibit this redoxcycling activity. The inhibition by metal cations is reversed by Tiron and that of the aromatic cations by Tiron and thyroxine. These inhibitors and activators affect authentic PQQ and the redox-activity of putative PQQ isolated from biological sources in a similar manner. This indicates that pyrroloquinoline quinone occurs naturally in animal tissues and fluids. PMID- 8216336 TI - Biosynthesis and processing of the platelet derived growth factor type alpha receptor. AB - The homodimers (AA, BB) of the platelet derived growth factor (PDGF) differentially interact with two highly related PDGF receptors (alpha, beta) that appear to mediate different functional responses in different cell types. To seek a basis for these apparent functional differences, we investigated the processing of the PDGF alpha-receptor. The PDGF alpha-receptor is rapidly glycosylated to a 160 kD form and undergoes a number of intermediate glycosylation steps that result in a mature form of 185 kD that appears at the cell surface within 60-90 minutes. The alpha receptor has a half-life of approximately 4 1/2 hours without and approximately 20 minutes in the presence of ligand. The processing steps of the alpha-receptor are similar to the processing of the PDGF beta receptor, suggesting that differential binding of signalling molecules to activated receptors may be responsible for the apparent functional differences in cellular responses to PDGF AA and PDGF BB. PMID- 8216337 TI - Biochemical correlates of longevity in two closely related rodent species. AB - The objective of this study was to explore the basis of variations in the life span and metabolic potential, i.e., total amount of energy consumed during life, between different species, in context of the free radical hypothesis of aging. A comparison was made between the house mouse (Mus musculus) and the white-footed mouse (Peromyscus leucopus): the latter has > 2-fold greater life span and metabolic potential than the former. Longer life span and higher metabolic potential of Peromyscus were associated with low rates of mitochondrial O2.- and H2O2 generation, higher activities of catalase and glutathione peroxidase and low levels of protein oxidative damage as well as low susceptibility to oxidative damage in response to experimental oxidative stress. Results support the role of oxidative stress in aging. PMID- 8216338 TI - Fluid shear stress induces synthesis and nuclear localization of c-fos in cultured human endothelial cells. AB - Quiescent cultured primary human umbilical vein endothelial cells were exposed to low levels (4 dynes/cm2) or arterial levels (25 dynes/cm2) of steady laminar shear stress for one hour. Intracellular c-fos protein was measured by immunocytochemistry and quantitative fluorescence video microscopy. The nuclear localized c-fos protein level was 5.4 +/- 2.0 fold higher (p < 0.01) in the cells exposed to arterial levels of shear stress as compared to the cells maintained in stationary culture. In contrast, the cells exposed to low levels of shear stress showed diffuse but slightly elevated levels of c-fos (2.4 +/- 0.73 times higher than control; p < 0.01) without preferential nuclear localization. The protein kinase C inhibitor, H7 (10 microM) significantly attenuated the induction of c fos by 50% in cells exposed to arterial shear stress for 1 hour. PMID- 8216339 TI - Inhibition of initiation of DNA replication in Xenopus egg extracts by a phosphatase inhibitor, calyculin A. AB - The protein phosphatase inhibitor calyculin A was found to strongly inhibit the DNA replication activity of Xenopus egg extracts in a dose-dependent manner. Calyculin A (0.8 nM) completely prevented the oscillation in DNA replication activity of mitotic extracts released by the addition of CaCl2. In contrast, in the case of extracts prepared from eggs activated by calcium ionophore A23187, calyculin A (0.8 nM) had no effect on the first peak of the oscillation in activity but inhibited the second peak of the oscillation. These results strongly suggest that calyculin A inhibits a protein phosphatase, which is involved in the initiation of DNA replication in the Xenopus egg extracts. PMID- 8216340 TI - Two new monoclonal antibodies against the alpha subunit of the human insulin-like growth factor-I receptor. AB - Recently, we have reported three monoclonal antibodies (mAbs) against purified human placental insulin-like growth factor (IGF)-I receptors. These antibodies, in contrast to the well-studied mAb alpha IR-3, stimulate binding of IGF-I and IGF-II to the receptor and DNA synthesis as well [Xiong, et al., Proc. Natl. Acad. Sci. U.S.A. 1992(89), 5356]. Here we describe two additional mAbs, 1H7 and 2C8, against the IGF-I receptor that have characteristics different from either alpha IR-3 or our previously reported mAbs. Both 1H7 and 2C8 bind to the alpha subunit of the IGF-I receptor as determined by immunoblotting. MAb 1H7 inhibited the binding of IGF-I and IGF-II to the IGF-I receptor while 2C8 had no effect on the binding of either ligand to the receptor. When their effects on DNA synthesis were examined using NIH 3T3 cells expressing human IGF-I receptors, 1H7 inhibited basal and IGF-I- or IGF-II-stimulated DNA synthesis whereas 2C8 stimulated basal DNA synthesis but provided no synergism in the presence of IGF-I or IGF-II. PMID- 8216341 TI - Insulin stimulates association of a 41kDa G-protein (GIR41) with the insulin receptor. AB - Insulin has a paradoxical effect on a 41kDa Gi-like protein: Although insulin treatment of rat adipocytes inhibited pertussis toxin-catalyzed ADP-ribosylation of a 41kDa G-protein in membranes in a dose-dependent manner, it simultaneously increased ADP-ribosylation of a 41kDa G-protein that co-immunoprecipitates with the insulin receptor (GIR41). The latter effect was insulin concentration- and time-dependent. The dose-dependent stimulatory effect of insulin on the autophosphorylation of the insulin receptor and on the ADP-ribosylation of the GIR41 in the insulin receptor immunoprecipitates closely paralleled each other. The time course of insulin-stimulated increase in the ADP-ribosylated GIR41, although rapid, was slower than the autophosphorylation of the receptor. The GIR41 is associated with and regulated by the insulin receptor further supporting an important role for this G-protein in modulating insulin action at the receptor level. PMID- 8216342 TI - Inhibitory interactions between stimulus-secretion pathways in the exocrine rat pancreas. AB - In many tissues the cellular responses mediated through different intracellular messenger systems are mutually interactive. In the exocrine pancreas the secretagogues acting via adenosine cyclic monophosphate (cAMP) and those acting via calcium-phosphoinositides can potentiate one another. On the other hand, protein kinase C (PK-C) modulates receptor-induced responses in exocrine pancreatic cells and other cell types. Recording total protein output, monitored on-line at 280 nm, from superfused rat pancreatic segments, we demonstrate that secretin (a cAMP-acting hormone) reduces the efficacy of the calcium-mediated secretagogue cholecystokinin-octapeptide (CCK-8). Likewise, the PK-C activator 12,O,tetradecanoyl phorbol 13 acetate (TPA) reduces both the efficacy of secretin and the potency of cholecystokinin. Thus, the hypothesis of potentiation between different stimulus-secretion coupling mechanisms must be revised, and receptor activated responses in the exocrine pancreas must be considered a complex model with multiple inhibitory and stimulatory interactions. PMID- 8216343 TI - The protective effect of copper complexes against gastric mucosal ulcer in rats. AB - The study examines the anti-ulcer activity of Cu(I)-(nicotinic acid)2Cl [CuCl(HNA)2]. A dose of 8 mg (23 mumol) of complex/kg body mass was suspended in 0.25% Tween-80 in saline solution and administered intragastrically to male Wistar albino rats which had developed gastric ulcers as a result of pyloric ligation (Shay-rat model). Another group of animals received 5 mg (25 mumol)/kg body mass of the copper-glycinate complex Cu(II)(glycinate)2 [Cu(II)(Gly)2]. Both protected as shown by reduction in the ulcer index, inhibition of gastric perforation and death. Significant increases in gastric juice volume and superoxide dismutase (SOD) activity in the gastric mucosa and blood plasma were found with both copper complexes, while the gastric juice prostaglandin E2 (PGE2) content was significantly decreased in the Cu(II)(Gly)2-treated group, it was significantly increased in the gastric mucosa of the CuCl(HNA)2-treated group. The copper complex-treated animals, especially those which received Cu(II)(Gly)2 had a marked fall in thromboxane A2 (TXA2) levels. These results suggest that intragastric administration of either CuCl(HNA)2 or Cu(II)(Gly)2 produced anti ulcerogenic activity, with different modes of action. PMID- 8216344 TI - Prostacyclin elevation following glutathione depletion in vivo. Possible threshold dependency in liver and lung. AB - The major objective of this study was to determine if a threshold level of glutathione (GSH) depletion is required to elevate plasma prostacyclin (6 ketoPGF1 alpha) in male Sprague-Dawley rats. Rats were treated i.p. with various doses of phorone, diethyl maleate (DEM), or GSH with and without DEM. Similar maximal depletions of hepatic GSH (to 10% of control) and renal GSH (to 50% of control) were observed with DEM and phorone, but lung GSH was depleted maximally by only 30% with phorone compared with a 70% depletion by DEM. Changes in lung GSH, but not kidney GSH, were closely correlated with changes in hepatic GSH 6 KetoPGF1 alpha levels in the lung were 10- to 30-fold higher than in kidney or liver, and there was a stronger correlation between lung and plasma 6-ketoPGF1 alpha than with the other two tissues. The increase in lung 6-ketoPGF1 alpha following GSH depletion did not appear to be due to a shift in prostaglandin metabolite synthesis since reciprocal changes in PGE2 were not observed; lung PGE2 levels were largely unaffected by DEM or phorone. Both DEM and phorone elevated plasma 6-ketoPGF1 alpha but the magnitude of increase for DEM (5- to 6 fold) was much greater than the 2-fold increase for phorone. The increase in plasma 6-ketoPGF1 alpha by 1.0 mL DEM/kg was attenuated by simultaneous administration of 2 mmol GSH/kg. The results indicate that the lung may be responsible for increases in plasma 6-ketoPGF1 alpha following GSH depletion and that a critical level of GSH depletion in the liver and/or lung may be necessary to elevate plasma 6-ketoPGF1 alpha levels. PMID- 8216345 TI - Bioreductive metabolism of AF-2[2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide] combined with 2-nitroimidazoles. Implications for use as hypoxic cell markers. AB - Metabolism of misonidazole under hypoxic conditions depletes the parent drug and causes about 4% of the reduced-drug-products to form adducts with cellular macromolecules (binding), and this process has been used to detect hypoxia in cells and tissues. The nitrofuran, AF-2 [2-(2-furyl)-3-(5-nitro-2 furyl)acrylamide] has been shown to increase both the metabolic depletion of misonidazole and its binding. In the present study, factors which might affect this process have been examined, in an in vitro system, to test the hypothesis that metabolic depletion of misonidazole could limit its ability to diffuse freely to the hypoxic cell population. Drastic reductions in glucose concentrations from their normal value of 5-10 mM to less than 0.5 mM had no significant effect on the metabolism of either misonidazole or AF-2. Similarly, glucose concentration did not influence the binding of misonidazole, even when concentrations of both oxygen (extreme hypoxia) and glucose were near zero--a very toxic biochemical environment. Similarly, the metabolism of the nitroheterocyclics had no effect on glucose consumption. The bioreductive depletion of misonidazole in extreme hypoxia appeared to be independent of drug concentration between 25 and 100 microM: this nearly zero-order rate of drug metabolism prevented the possibility of working at constant drug concentration. AF-2 exacerbated this effect by greatly enhancing the metabolic depletion of misonidazole. AF-2 was found to increase both the metabolic depletion and binding of misonidazole by the same factor. An unexpected finding was that metabolism of etanidazole, a 2-nitroimidazole closely related to misonidazole, was not enhanced by AF-2. Micromolar amounts of oxygen inhibited the reductive activation of AF-2, and also the interaction between AF-2 and misonidazole. Our results suggest that metabolic depletion of nitroheterocyclics could influence their ability to diffuse adequately to hypoxic tissues, particularly at the low drug concentrations that have been used to measure tissue hypoxia in vivo. PMID- 8216346 TI - Mechanism of poloxamer 407-induced hypertriglyceridemia in the rat. AB - One 300 mg i.p. injection of the nonionic surfactant poloxamer 407 (Pluronic F 127) produces a significant increase above control of both circulating cholesterol and triglyceride (TG) concentrations. The present study was conducted to determine the effect of poloxamer 407 (P-407) on the capacity to hydrolyze circulating TG by lipoprotein lipase (LPL) in an attempt to determine the mechanism of action of P-407. The concentration of TG in the rat following a single 300 mg i.p. injection of P-407 was marked, increasing from 84 +/- 10 to 3175 +/- 322 mg/dL at 24 hr. The maximal rate of TG accumulation (5.74 mg/dL/min) in the plasma of P-407-injected rats occurred between 2 and 4 hr post-injection. In vitro incubation of LPL with P-407 significantly inhibited enzyme activity with an inhibitory concentration at which 50% of the enzymatic activity was lost of approximately 24 microM. Concentrations of P-407 exceeding 350 microM in vitro completely inhibited LPL activity. The effects of P-407 on the enzymatic activity of LPL in post-heparin plasma obtained following a single 300 mg dose of P-407 to rats demonstrated greater than 95% suppression of LPL activity 3 hr post injection compared with controls. Inhibition of LPL activity was greater than 90% as long as 24 hr following a single i.p. injection of P-407. However, while the heparin-releasable fraction of capillary-bound LPL was inhibited in the plasma, LPL activity significantly increased in cardiac and skeletal muscle in poloxamer injected animals compared with sham-injected controls. Although there was no significant change in LPL activity in adipose tissue, testes, and lung resulting from P-407 treatment, LPL activity increased by 37% in myocardium, 69% in soleus, and 66% in gastrocnemius muscle in P-407-injected rats when compared with controls. Our studies would suggest that the predominant mechanism by which P-407 induced an increase in circulating TG was by a reduction in the rate at which TG was hydrolyzed due to inhibition of heparin-releasable LPL by the surfactant. PMID- 8216347 TI - NADPH-dependent enzyme-catalyzed reduction of aldophosphamide, the pivotal metabolite of cyclophosphamide. AB - One of the metabolites found in the urine of mammals given the prodrug cyclophosphamide is alcophosphamide, an alcohol. It is most probably generated from cyclophosphamide via aldophosphamide, an aldehyde which otherwise can directly give rise to phosphoramide mustard; the latter effects the cytotoxic action of cyclophosphamide and other oxazaphosphorines. It has already been demonstrated that horse liver alcohol dehydrogenase catalyzes the reduction of aldophosphamide to alcophosphamide. Herein, we report that aldose reductase and aldehyde reductase purified from human placenta also catalyze this reaction. The Km values for aldose reductase- and aldehyde reductase-catalyzed reduction of aldophosphamide to alcophosphamide were 0.15 and 1.6 mM, respectively. Aldose reductase and aldehyde reductase accounted for 94 and 6%, respectively, of total placental pyridine nucleotide-dependent enzyme-catalyzed aldophosphamide (160 microM) reduction. Aldose reductase-catalyzed reduction of aldophosphamide appeared to be noncompetitively inhibited by sorbinil; the Ki value was 0.4 microM. The in vivo significance of these observations is uncertain but could be of some magnitude since alcophosphamide is known to be only weakly cytotoxic. PMID- 8216348 TI - Mechanism of uptake of the phosphonate analog (S)-1-(3-hydroxy-2 phosphonylmethoxypropyl)cytosine (HPMPC) in Vero cells. AB - The cellular uptake of phosphonylmethoxypropyl cytosine (HPMPC) was characterized to gain insight into the molecular properties that allow this anticytomegalovirus drug to permeate cell membranes. The time course of uptake of HPMPC into Vero cells was linear between 10 and 75 min and proportional to the concentration in the medium from 10(-6) to 10(-2) M. HPMPC uptake was temperature sensitive and the rate of uptake was considerably lower at 27 degrees than at 37 degrees and almost totally inhibited at 4 degrees. In competition studies with naturally occurring nucleosides, nucleotides or the phosphonylmethoxyethyl derivatives, none affected the uptake of HPMPC at concentrations up to 2000-fold molar excess. The uptake of [3H]HPMPC into Vero cells was compared with that of [14C]sucrose, a probe for fluid-phase endocytosis. Kinetics for both compounds were very similar, as were the effects of the microtubule antagonist colchicine and the tumor promoting agent phorbol myristate acetate. Colchicine and the phorbol ester are known to, respectively, inhibit and stimulate endocytosis. It is concluded from these data that HPMPC enters Vero cells by fluid-phase endocytosis and that once internalized it may accumulate in the lysosome. Protonation of the negative charge on the phosphonyl group in HPMPC may allow its diffusion across the lysosome membrane and eventual activation to its putative active diphosphorylated form in the cell cytoplasm. PMID- 8216349 TI - Nuclear magnetic resonance studies of the binding of captopril and penicillamine by serum albumin. AB - The metabolism of the thiol-containing drugs penicillamine (beta,beta dimethylcysteine) and captopril (D-3-mercapto-2-methylpropanoyl-L-proline) involves the formation of mixed disulfides, including mixed disulfides with serum albumin. The reactions of penicillamine and captopril with serum albumin in aqueous solution and in intact human blood plasma have been studied by 500 MHz 1H NMR spectroscopy. Penicillamine was found to react rapidly at the albumin cysteine mixed disulfide bond to form penicillamine-cysteine mixed disulfide and to react more slowly at other albumin disulfide bonds. The amino acid cysteine was found to react with albumin by the same two pathways. In contrast, captopril rapidly associates with albumin to form noncovalent albumin-captopril complexes. Exchange of captopril between its free and noncovalently bound forms takes place on the NMR time scale. On a longer time scale, captopril reacts with albumin by thiol/disulfide interchange reactions. Noncovalently bound captopril displaced lactate from its albumin binding sites, both in aqueous solution and in human plasma. The results demonstrate that 1H NMR is a useful method for characterizing the state of drug molecules in human plasma and for detecting and monitoring perturbations by drugs of delicately balanced binding equilibria involving endogenous small molecules and macromolecules in plasma. PMID- 8216350 TI - Prevention of insulin-dependent diabetes mellitus by 2'-deoxycoformycin in the BB Wistar rat. AB - The effect of the adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (dCF) on the development of insulin-dependent diabetes mellitus (IDDM) was assessed in the BB Wistar rat. Sixty-one male rats were treated from days 30 to 120 with 0, 0.5, 1.0 or 1.5 mg dCF/kg/week. The incidence of IDDM was 78% in the controls and was significantly (P < 0.01) decreased in rats receiving 1.5 mg dCF/kg/week (32%), but not in rats receiving lower doses of the drug. However, for those rats that became diabetic the mean time to the development of IDDM was unchanged in animals receiving dCF compared with control. dCF treatment did not produce significant weight loss in the animals or gross changes in the thymus, spleen or kidneys. Although the protective effect of dCF against IDDM was likely produced by immunosuppression, the different dCF dosages had similar effects on ADA suppression in spleen or thymus and on dATP accumulation in these organs. PMID- 8216351 TI - Chlorotrifluoroethylene trimer and tetramer are inducers of the CYP4A subfamily. AB - Male Wistar albino rats were treated for a 7 day period with equimolar doses of the trimer and tetramer oligomers of chlorotrifluoroethylene (CTFE), resulting in significant hepatomegaly for both compounds. In addition, both trimer and tetramer significantly induced the peroxisomal beta-oxidation of fatty acids as assessed by increases in palmitoyl-coenzyme A (CoA) oxidation, thus confirming these oligomers as peroxisome proliferators. Consistent with these conclusions, both trimer and tetramer increased the hydroxylation of lauric acid indicating that the CTFEs were inducers of the CYP4A subfamily, a conclusion further supported by substantial increases in the steady-state levels of the cognate CYP4A1 mRNA as determined by northern blotting. The liver appeared to be more susceptible to induction than the kidney and the CTFE tetramer was more potent than the trimer. These results are discussed with respect to both the differential hepatotoxicity, and biotransformation/disposition of the two polyhalogenated oligomers. PMID- 8216352 TI - Preventive effect of gomisin A, a lignan component of shizandra fruits, on acetaminophen-induced hepatotoxicity in rats. AB - The preventive effect of gomisin A, a lignan component of shizandra fruits, on acetaminophen-induced hepatotoxicity in rats was examined by histological and biochemical analysis. Acetaminophen at a dose of 750 mg/kg was administered to male Wistar rats with or without pretreatment with 50 mg/kg of gomisin A. Gomisin A inhibited not only the elevation of serum aminotransferase activity and hepatic lipoperoxides content, characteristic of acetaminophen administration, but also the appearance of histological changes such as degeneration and necrosis of hepatocytes. However, gomisin A did not affect the decrease in liver glutathione content. These results suggest that gomisin A protects the liver from injury after administration of acetaminophen through the suppression of lipid peroxidation. PMID- 8216353 TI - Alterations of growth factor transcripts in rat lungs during development of monocrotaline-induced pulmonary hypertension. AB - Although pathologic and hemodynamic changes in monocrotaline (MCT)-induced pulmonary hypertension have been studied extensively, relatively little is known about the inter- and intracellular signaling mechanisms underlying such alterations. As a first step to delineating signaling mechanisms governing adverse structural alterations in the hypertensive lungs, we examined changes in the steady-state levels of mRNAs encoding several growth factors including transforming growth factors (TGF), platelet-derived growth factors (PDGF), vascular endothelial cell growth factor (VEGF) and endothelin (ET) as a function of time in MCT-induced pulmonary hypertension in rats. These studies demonstrated a very diverse pattern of growth factor gene expression in response to MCT administration. In general, alterations in the steady-state levels of mRNAs encoding the growth factors preceded the onset of MCT-induced pulmonary hypertension. TGF-beta 1, -beta 2 and -beta 3 transcripts were seen to be elevated, whereas that of TGF-alpha and PDGF-A remained unchanged. Transcripts for PDGF-B and ET were increased in the early stages but declined to less than controls in the latter stages of MCT-induced hypertension. In contrast, levels of VEGF mRNA decreased to less than controls as the disease progressed. Viewed collectively, the diverse pattern of expression suggests that alterations in the levels of the growth factor transcripts may have a significant role in the development of pulmonary hypertensive disease and may be relevant to the pathological and structural changes in MCT-induced pulmonary hypertension. PMID- 8216354 TI - Identification of a new vascular smooth muscle contracting polypeptide in Phoneutria nigriventer spider venom. AB - The fractionation of Phoneutria nigriventer spider venom by gel filtration (Sephadex G-10-120) followed by ion-exchange chromatography (microgranular CM cellulose-52) resulted in sixteen fractions (CI to CXVI) from which CVII+VIII, CIX and CX+XI caused dose-dependent and short-lived contractions of both arterial and venous rabbit vessels. Fraction CX+XI was further purified by a reverse phase HPLC, and a contractile polypeptide (PNV2) was isolated. The amino terminal sequence of PNV2 (LAKRADICQPGKTSQRACET) indicated that it represents a pure polypeptide consisting of a single chain. Furthermore, the amino acid analysis of PNV2 revealed the presence of four disulfide bridges, a high content in Lys (14%), Glx (11%), and the absence of His. The global amino acid composition showed that this polypeptide is composed of 102 residues (Trp not included) with a calculated molecular weight of 12,114. Whether this peptide is responsible for the vascular alterations observed in Phoneutria envenomation, such as lung edema and priapism, remains to be further investigated. PMID- 8216355 TI - Different biotransformation of morphine in isolated liver cells from guinea pig and rat. AB - The biotransformation of morphine was characterized in freshly isolated parenchymal and non-parenchymal liver cells from rats and guinea pigs in suspension culture to establish an in vitro model for morphine metabolism. Liver cells were prepared by a collagenase perfusion technique, and separated by differential centrifugation. Morphine metabolism was investigated at different concentrations (1, 5, 100 and 200 microM). Samples were taken repeatedly during 2 4 hr of incubation, and subsequently analysed on a HPLC system employing both UV and electrochemical detection. In suspensions of hepatocytes from both animal species morphine-3-glucuronide (M3G) was the major metabolite of morphine, and was formed at comparable rates at all concentrations examined. Guinea pig hepatocytes in addition produced considerable quantities of morphine-6 glucuronide (M6G), whereas this metabolite was detected only intracellularly in minor quantities in rat hepatocytes. The ratio between the two morphine glucuronides (M3G/M6G) in suspensions of guinea pig hepatocytes was approximately 4:1. N-Demethylation of morphine was more pronounced per mg cell protein in rat hepatocytes compared to guinea pig cells. Metabolic activity towards morphine was not detected in non-parenchymal cells of the two species. The morphine glucuronidation pattern found in guinea pig hepatocytes resembles to a greater extent than that found in rat hepatocytes the pattern found in in vivo studies of humans. It was concluded that isolated guinea pig parenchymal cells appeared to be a promising in vitro system for studies of morphine glucuronidation, and to observe metabolism in general. PMID- 8216356 TI - Induction of spermidine/spermine N1-acetyltransferase in human breast carcinoma cells. A possible role for calcium. AB - Methylglyoxal bis(guanylhydrazone) (MGBG) a structural analogue of spermidine produced a dose-dependent induction of cytosolic spermidine/spermine N1 acetyltransferase (N1-SAT) in the human breast carcinoma cell line, T47-D. Intracellular accumulation of MGBG was found to be saturable and the drug produced characteristic effects on intracellular polyamines, decreasing spermidine and spermine content, with concomitant increases in putrescine levels. The MGBG-induced increase in N1-SAT activity was potentiated by both tetronasin, a calcium ionophore, and felodipine, a calcium channel blocking agent. Only tetronasin was an active inducer of the enzyme when used alone. Both drugs influenced intracellular MGBG content but in opposite directions: tetronasin increased MGBG content while felodipine decreased it. Therefore, the potentiation of N1-SAT induction is not simply the result of increased intracellular accumulation of MGBG but is more likely to be related to the concentration of intracellular free calcium in these cells. PMID- 8216357 TI - In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase. AB - Aldehyde oxidase was purified about 120-fold from rat liver cytosol by sequential column chromatography using diethylaminoethyl (DEAE) cellulose, Benzamidine Sepharose 6B and gel filtration. The purified enzyme was shown as a single band with M(r) of 2.7 x 10(5) on polyacrylamide gel electrophoresis (PAGE) and M(r) of 1.35 x 10(5) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Using this purified enzyme, in vitro conversion of allopurinol, pyrazinamide and pyrazinoic acid was investigated. Allopurinol and pyrazinamide were oxidized to oxypurinol and 5-hydroxy-pyrazinamide, respectively, while pyrazinoic acid, the microsomal deamidation product of pyrazinamide, was not oxidized to 5 hydroxypyrazinoic acid. The apparent Km value of the enzyme for pyrazinamide was 160 microM and that for allopurinol was 1.1 mM. On PAGE, allopurinol- or pyrazinamide-stained band was coincident with Coomassie Brilliant Blue R 250 stained band, respectively. These results suggest that aldehyde oxidase may play a role in the oxidation of allopurinol to oxypurinol and that of pyrazinamide to 5-hydroxypyrazinamide with xanthine dehydrogenase which can oxidize both allopurinol and pyrazinamide in vivo. The aldehyde oxidase may also play a major role in the oxidation of allopurinol and pyrazinamide in the subgroup of xanthinuria patients (xanthine oxidase deficiency) who can oxidize both allopurinol and pyrazinamide. PMID- 8216358 TI - Metabolism of antipyrine in vivo in two rat models of liver cirrhosis. Its relationship to intrinsic clearance in vitro and microsomal membrane lipid composition. AB - Antipyrine metabolism depends on at least three isoenzymes of cytochrome P450 forming the main metabolites 3-OH-, 4-OH- and norantipyrine. We investigated to what extent antipyrine clearance and metabolite formation are impaired in two models of liver cirrhosis in the rat, namely micronodular cirrhosis induced by chronic exposure to phenobarbital/CCl4 and biliary cirrhosis induced by bile duct ligation. Salivary antipyrine clearance was decreased to a similar extent in cirrhosis induced by CCl4 and bile duct ligation (-35%). Clearance for production of 3-OH-antipyrine was decreased in both models, while 4-hydroxylation was maintained. Metabolic clearance of both 3-OH-antipyrine and 4-OH-antipyrine in vivo correlated with their clearance in vitro (r = 0.658 and r = 0.583) but not with that of norantipyrine. The microsomal cholesterol content was increased by 16% and 90% in CCl4 and bile duct-ligated cirrhotic rats (P < 0.001), respectively. Membrane fluidity, expressed as the ratio of phospholipids to cholesterol, correlated with the in vivo clearance for production of norantipyrine (r = 0.841) but not of 3-OH- or 4-OH-antipyrine, while clearance in vitro was not related to altered lipid composition. Our results demonstrate that the cytochrome P450 isoenzymes responsible for the different pathways of antipyrine metabolism are affected to different extents by cirrhosis. Alterations in intrinsic clearance explain only part of the loss of hepatocellular function. Altered lipid composition contributes to this loss of function but other factors, among them loss of hepatocytes and changes in microcirculation, could be more important determinants of the decrease in xenobiotic metabolism in cirrhosis. PMID- 8216359 TI - A novel pathway for formation of thiol metabolites and cysteine conjugates from cysteine conjugate sulphoxides. AB - p-Bromothiophenol and S-(p-bromophenyl)-L-cysteine were formed enzymatically from S-(p-bromophenyl)-L-cysteine sulphoxide in the in vitro systems with isolated rat hepatocytes or purified cysteine conjugate beta-lyases. Isotope dilution study with non-radiolabelled carrier of each product suggested the initial liberation of the thiol and subsequent formation of the cysteine conjugate. C-S bond cleavage pathway to liberate sulphenic acid and thiol are postulated to play an important role in in vivo generation of toxic intermediates and products from cysteine conjugates. PMID- 8216360 TI - Mouse brain opioid receptor identification by direct ultraviolet photoaffinity labeling. AB - [3H]Morphine, PL-017[prolyl-3,4-3H,D-prolyl,3,4-3H] ([3H]PL-017) and enkephalin (2-D-penicillamine,5-D-penicillamine)[tyrosyl-2,6-3H] ([3H]DPDPE) were directly cross-linked to mouse brain opiate receptors by an ultraviolet (254 nm) irradiation procedure. [3H]Morphine preferentially and specifically labeled a 58 kDa protein. The labeling of this protein was suppressed by the addition of excess naloxone. Dithiothreitol reduced the irreversible binding of [3H]morphine and [3H]PL-017 to the receptor protein. In the acid hydrolysate of [3H]DPDPE labeled opiate receptors, dityrosine, was detected. These results suggest that the [3H]tyrosine residue of [3H]DPDPE covalently bound the tyrosine residue of delta-opioid receptors. The direct UV-photoaffinity labeling method using commercially available radioactive opiates described here should be a useful tool for characterization and purification of the opiate receptors. PMID- 8216361 TI - Human xenobiotic metabolizing esterases in liver and blood. AB - Esterases in human liver microsomes hydrolysed fluazifop-butyl (Vmax 9.8 +/- 1.6 mumol/min/g tissue), paraoxon (Vmax 47.4 +/- 7.5 nmol/min/g tissue) and phenylacetate (Vmax 57 +/- 8 mumol/min/g tissue), whereas esterases found in the human liver cytosol hydrolysed fluazifop-butyl (Vmax 10.0 +/- 0.5 mumol/min/g tissue) and phenylacetate (Vmax 37 +/- 2.9 mumol/min/g tissue) but not paraoxon. Human plasma esterase hydrolysed fluazifop-butyl (Vmax 0.09 +/- 0.006 mumol/min/mL), paraoxon (Vmax 210 +/- 14 nmol/min/mL) and phenylacetate (Vmax 250 +/- 17 mumol/min/mL). Inhibitory studies using paraoxon, bis-nitrophenol phosphate and mercuric chloride indicated fluazifop-butyl hydrolysis involved carboxylesterase in liver microsomes and cytosol, and cholinesterase and carboxylesterase in plasma. Phenylacetate hydrolysis involved arylesterase in plasma, both arylesterase and carboxylesterase in liver microsomes and carboxylesterase in liver cytosol. Plasma hydrolysis is less important and overall esterase activity is lower in humans than in the rat which is therefore a poor model. PMID- 8216362 TI - A novel role for carboxylesterase in the elevation of cellular cysteine by esters of cysteine. AB - Esters of cysteine, such as cysteine isopropylester (CIPE) or cysteine cyclohexylester (CCHE), are efficient delivery systems for cysteine to cells. After enzymic cleavage, the esters of cysteine provide a source of cellular cysteine, which may support reduced glutathione (GSH) synthesis and/or act as a direct chemoprotectant. Reducing esterase activity of rat lung slices or isolated hepatocytes with paraoxon or bis(4-nitrophenyl) phosphate or by reducing the temperature to 4 degrees dramatically altered the metabolism of esters of cysteine; the initial increase in cellular cysteine was slowed, the residency time of cysteine esters in the extracellular pool was prolonged without substantially enhancing the levels of intracellular ester. Incubation of lung slices with CIPE at 4 degrees led to a marked increase in cellular cysteine, which prior inhibition of esterase activity abolished. Inhibiting the neutral amino acid uptake systems, ASC and L, while effecting the uptake of cysteine, did not reduce the elevation of cellular cysteine by CIPE. We propose that the elevation of cellular cysteine by esters of cysteine may be mediated by membrane associated esterase activity. PMID- 8216363 TI - Aminoguanidine: a drug proposed for prophylaxis in diabetes inhibits catalase and generates hydrogen peroxide in vitro. AB - Aminoguanidine (AG) has been proposed as a drug of potential benefit in prophylaxis of the complications of diabetes. We show here that AG irreversibly inhibits catalase with an efficacy similar to aminotriazole. AG also produces hydrogen peroxide, in a transition metal-catalysed process which may be partially dependent upon prior hydrolysis of AG to semicarbazide and hydrazine. These observations may be of importance in proposals for the long term administration of AG in diabetes. PMID- 8216364 TI - Effects of morphine and its metabolites on opiate receptor binding, cAMP formation and [3H]noradrenaline release from SH-SY5Y cells. AB - Opiate receptor occupation leads to a variety of intracellular events including inhibition of adenylyl cyclase and cAMP formation. We have examined the opiate binding characteristics, effects on cAMP formation and [3H]noradrenaline release of morphine, morphine-6 (M6G) and -3 (M3G)-glucuronides, and fentanyl in SH-SY5Y human neuroblastoma cells. M6G and M3G are the major metabolites of morphine formed in vivo whose cellular action remains to be fully elucidated. In binding experiments morphine (affinity, K50 = 96 nM) and fentanyl (K50 = 99 nM) were more potent than M6G (K50 = 393 nM), while M3G was inactive. However, for cAMP inhibition morphine (half maximum inhibition, IC50 = 193 nM) and M6G (IC50 = 113 nM) were roughly equipotent, with fentanyl (IC50 = 27 nM) being more potent and producing a greater maximum inhibition (56%). M3G was inactive. These in vitro data are in general agreement with the in vivo effects of these glucuronides. Moreover, all of the opiates tested failed to inhibit K(+)-evoked release of [3H]noradrenaline. Whilst these data do not support a role for cAMP in neurotransmitter release, alterations in cAMP formation may still have a role to play in the mechanism of analgesia. PMID- 8216365 TI - Metabolism of cyclosporine after orthotopic liver transplantation. AB - The aim of this work was to determine whether the extensive metabolism of cyclosporine, acquired in a donor by treatment with an inducer of cytochrome P450 3A (P450 3A) (cyclosporine oxidase), was transmissible to the recipient by orthotopic liver transplantation. For this purpose, male Wistar rats were divided into five groups including: control animals (group C), animals treated with dexamethasone (an inducer of P450 3A, 50 or 300 mg/kg/day, for 4 days, group D), animals transplanted with the livers of control rats (group G) or with the livers of dexamethasone-induced rats (group GD), and animals treated with beta naphthoflavone (an inducer of P450 1A, group B). All animals received a single i.v. dose of 10 mg/kg cyclosporine 24 hr after either the last dose of inducer or the transplantation. For each group of animals, the area under the curve (AUC) of cyclosporine was calculated from the curves of blood cyclosporine levels (by radioimmunoassay) against time; liver microsomes were assayed for cyclosporine oxidase activity by HPLC, erythromycin demethylase and P450 3A level by western blot with specific anti-P450 3A antibodies. The decrease in the AUC in groups D and GD with respect to C and G was correlated with increased level of P450 3A (4 5-fold with respect to control) as well as of microsomal cyclosporine oxidase. In addition, cyclosporine oxidase activity of liver microsomes was specifically inhibited by anti-P450 3A antibodies and troleandomycin. The animals in group B did not exhibit increased metabolism of cyclosporine either in vivo or in vitro. We conclude that: (1) cyclosporine is predominantly oxidized in the rat liver by a form of P450 from the 3A subfamily; (2) the extensive metabolism of cyclosporine acquired by donor rats after treatment with dexamethasone is transmissible to the recipients through orthotopic liver transplantation. PMID- 8216366 TI - Binding studies with recombinant human serum albumin obtained by expression of a synthetic gene in yeast. Stereoselective binding and allosteric interaction with benzodiazepine and coumarin ligands. AB - The specific ligand binding ability of recombinant human serum albumin produced in yeast using the synthetic gene was studied by affinity chromatographic method. It was found that synthetic protein possesses those stereoselective binding and binding interactions for several chiral benzodiazepine and coumarin compounds which are characteristic of the natural human serum albumin, suggesting identical tertiary structures. PMID- 8216367 TI - Inhibition of collagen-induced platelet aggregation and adhesion by a pseudocyanide derivative of avicine isolated from Zanthoxylum integrifoliolum Merr. AB - Avicine pseudocyanide, a derivative of avicine isolated from Zanthoxylum integrifoliolum Merr., inhibited collagen-induced platelet aggregation and release reaction in a concentration-dependent manner. Trimucytin is a collagen like snake venom protein isolated from Trimeresurus mucrosquamatus. Avicine pseudocyanide also inhibited trimucytin (1 microgram/mL)-induced platelet aggregation and release reaction concentration dependently. The IC50 values of avicine pseudocyanide on collagen (10 micrograms/mL)- and trimucytin (1 microgram/mL)-induced platelet aggregation were 47.3 +/- 4.1 and 62.5 +/- 5.6 microM, respectively. Avicine pseudocyanide at a concentration of 300 microM inhibited less than 30% of platelet aggregation induced by ADP (20 microM), AA (100 microM), U46619 (1 microM), PAF (2 ng/mL) and thrombin (0.1 U/mL). The concentration-response curve of collagen-induced platelet aggregation was shifted to the right by avicine pseudocyanide (20-100 microM) concentration dependently. The Schild plot showed that pA2 and pA10 values of avicine pseudocyanide were 4.8 and 4.3, respectively, with slope of -1.9. Avicine pseudocyanide also inhibited collagen (10 micrograms/mL)-induced aggregation of rabbit whole blood with an IC50 of 145 +/- 13 microM. Collagen-induced thromboxane B2 formation was also inhibited by avicine pseudocyanide in a concentration-dependent manner with a maximal effect at 100 microM. However, arachidonic acid (AA)-induced thromboxane B2 and prostaglandin D2 formations were only partially suppressed by a high concentration of avicine pseudocyanide (300 microM). Avicine pseudocyanide (100 microM) inhibited the [3H]inositol monophosphate formation and the rise of intracellular Ca2+ concentration caused by collagen but not those caused by AA, U46619, platelet-activating factor and thrombin. In the presence of prostaglandin E1, Mg(2+)-dependent platelet adhesion to collagen was inhibited by avicine pseudocyanide with an IC50 of 278 +/- 16 microM. These data indicate that avicine pseudocyanide is an inhibitor of collagen-induced platelet aggregation and platelet-collagen adhesion. PMID- 8216368 TI - Studies on the reactivity of acyl glucuronides--V. Glucuronide-derived covalent binding of diflunisal to bladder tissue of rats and its modulation by urinary pH and beta-glucuronidase. AB - Acyl glucuronide conjugates of acidic drugs have been shown to be reactive metabolites capable of undergoing non-enzymic hydrolysis, rearrangement (isomerization via acyl migration) and covalent binding reactions with plasma protein. In an earlier study (King and Dickinson, Biochem Pharmacol 45: 1043 1047, 1993), we documented formation of covalent adducts of diflunisal (DF), a salicylate derivative which is metabolized in part to a reactive acyl glucuronide (DAG), with liver, kidney, skeletal muscle and small and large intestine (in addition to plasma protein) of rats given the drug i.v. twice daily at 50 mg DF/kg for 7 days. The present study shows that covalent adducts of DF were also formed with urinary bladder tissue of these rats, achieving concentrations (ca. 5 micrograms DF equivalents/g tissue) higher than those found in the other tissues noted above. After cessation of dosing, the adduct concentrations declined with an apparent T 1/2 value of ca. 20 hr. Adducts were also formed ex vivo in excised rat bladders in which DAG or a prepared mixture of its acyl migration isomers (iso-DAG) were incubated at pH 5.0, 6.5 and 8.0. After 8 hr incubation, the highest concentrations (ca. 11 micrograms DF equivalents/g) were produced with iso-DAG at pH 5.0, and the lowest (ca. 2.3 micrograms DF equivalents/g) with DAG at pH 5.0. However, a major competing reaction for DAG (at least at pH 5.0) was hydrolysis by beta-glucuronidases originating from bladder tissue. By contrast, iso-DAG was quite resistant to such hydrolysis. The phenolic glucuronide conjugate, another important metabolite of DF, was hydrolysed only slowly. Similar results were obtained in fresh rat urine adjusted to pH 5.0. The results support covalent DF adduct formation in rat bladder originating from both DAG and iso-DAG as ultimate reactants, though the extent of binding is modulated by both urinary pH and beta-glucuronidases. PMID- 8216369 TI - Cytochrome P450 2C9 is responsible for hydroxylation of the naphthoquinone antimalarial drug 58C80 in human liver. AB - 2-(4-t-Butylcyclohexyl)-3-hydroxy-1,4-naphthoquinone (58C80) is an experimental naphthoquinone antimalarial drug which undergoes extensive alky hydroxylation in man. By means of purification, N-terminal amino acid sequencing and inhibition by antibodies and sulfaphenazole, we have identified the form of cytochrome P450 primarily responsible for 58C80 hydroxylation in human liver, P450hB20-27, to be a member of the P450 2C9 subfamily. P450hB20-27 is a low-spin haemoprotein with molecular mass 54 kDa. 58C80 hydroxylation in human liver microsomes was dependent on either NADPH or NADH, with the activity supported by NADH being 35% of that supported by NADPH. With purified P450hB20-27 cytochrome b5 stimulated the NADH-dependent activity 8-fold but inhibited the NADPH-dependent activity by 30%. 58C80 is a novel substrate structure for human P450 2C and these results significantly broaden the range of drugs which have been directly shown (i.e. using a purified enzyme as opposed to expressed cDNA) to be metabolized by human P450 2C forms that are incontrovertibly expressed in human liver in vivo. PMID- 8216370 TI - Potentiation of TNF-mediated cell killing by mitoxantrone. Relationship to DNA single-strand break formation. AB - Tumor necrosis factor (TNF) is a pleiotropic cytokine that mediates different cellular responses including cytotoxicity, cytostasis, proliferation, differentiation and expression of specific genes. Recent studies have demonstrated that chemotherapeutic drugs that inhibit the nuclear enzyme DNA topoisomerase II synergize with TNF in tumor cell killing in vitro and in vivo. We now report that a combination of TNF and the topoisomerase II inhibitor Mitoxantrone produced dose-dependent synergistic cytotoxicity against the human ovarian cancer cell line A2774 in a clonogenic assay (1 hr treatment). This result was obtained with simultaneous administration of the drug and the cytokine under test, and is independent of modification of Mitoxantrone uptake. This combination is responsible for an evident augmentation of "cleavable complex" formation. From isolated nuclei, we have isolated also the topoisomerase II activity; we observed an increment when the cells were previously treated with TNF, 2.5 min before nuclear extraction. After 10-30 min of treatment with TNF, the topoisomerase II activity returned to normal values. If TNF is not given with but 30 min before Mitoxantrone, no potentiation of cytotoxicity or break induction is observed. These results suggest that specific timing of the association may be needed also when attempting to translate it to animals and humans. PMID- 8216371 TI - Organic solvents increase membrane fluidity and affect bile flow and K+ transport in rat liver. AB - Following the earlier observation that inhalation of volatile lipid solvents and of narcotic gases causes cholestasis, we studied the effects of various organic solvents on bile flow, plasma membrane fluidity and potassium movement in rat liver. Both in vivo and in the isolated perfused liver, applications of CCl4, CHCl3, dichloromethane, trichloroethylene, halothane, benzene and cyclohexane elicited rapid and sustained but reversible cholestasis. A transient phase of choleresis was observed prior to and after cholestasis, during the increase and fall in liver tissue solvent concentrations, respectively. Tissue concentrations required to produce cholestasis were lower the higher the lipophilicity of the solvent. Membrane fluidity was measured in isolated basolateral liver cell membranes by fluorescence polarization. Fluidity increased with increasing solvent concentration, the increase being associated with either biphasic stimulation and inhibition of membrane enzymes (Na+,K(+)-ATPase, 5'nucleotidase) or with inhibition alone (Mg(2+)-ATPase). In the isolated perfused liver, application of organic solvents caused hepatic uptake of K+ that was followed by K+ release upon withdrawal of the solvent. The magnitude of K+ uptake elicited by the solvent was comparable with the effect of blocking K+ channels with 2 mM Ba2+, but Ba2+ was ineffective in the presence of the solvent. In contrast, application of ouabain caused K+ release in equal amounts in the absence and presence of the solvent, indicating that K+ uptake elicited by the solvent results from inhibition of K+ efflux through K+ channels rather than stimulation of the Na+,K+ pump. The data show that cholestasis elicited by lipid solvents is associated with an increase in membrane fluidity and with disturbance of liver K+ homeostasis. The significance of these observations is discussed with respect to other models of experimental cholestasis. PMID- 8216372 TI - Conversion of 4-nitroquinoline 1-oxide (4NQO) to 4-hydroxyaminoquinoline 1-oxide by a dicumarol-resistant hepatic 4NQO nitroreductase in rats and mice. AB - The product formed from 4-nitroquinoline 1-oxide (4NQO), a potent carcinogen, by the action of mouse NADH:4NQO nitroreductase NR-1 was directly identified as 4 hydroxyaminoquinoline 1-oxide (4HAQO) by high performance liquid chromatography analyses in two systems. In liver cytosols from both male and female mice, NADH:4NQO nitroreductase was the predominant enzyme catalyzing the reduction of 4NQO. Rat liver cytosol catalyzed the conversion of 4NQO to either 4HAQO or a glutathione conjugate depending upon coenzyme or cosubstrate availability. Whereas NAD(P)H:quinone reductase (NAD(P)H:(quinone acceptor) oxidoreductase; DT diaphorase; EC 1.6.99.2) was the predominant 4NQO reductase present in liver cytosol from Sprague-Dawley rats, dicumarol-resistant NADH:4NQO nitroreductase specific activities were comparable with those of mouse liver cytosols. A 4NQO nitroreductase from rat liver cytosol was separated from NAD(P)H:quinone reductase chromatographically and shown to have a strong preference for NADH and to be insensitive to inhibition by dicumarol. PMID- 8216373 TI - Polyclonal antibody generation in rabbit by administration of an organophosphorus acid anhydrolase (OPAA) from squid. AB - When a nerve gas hydrolyzing enzyme [organophosphorus acid anhydrolase (OPAA), formerly DFPase] purified from squid hepatopancreas was injected into rabbits, the resulting sera (RAS) inhibited OPAA purified from either squid hepatopancreas or squid optic ganglia. The inhibition was non-competitive, with 50% inhibition at a 1:1,000 serum dilution, and with the limit of inhibition (in effect, a "titer") at approximately 1:10,000. This RAS did not inhibit the distinctly different OPAAs from a mammalian and two bacterial sources. The hepatopancreas generated RAS also reacted positively to the appropriate enzyme-linked immunosorbent assay (ELISA) at a titer of 1:100,000. In marked contrast, when OPAA purified from squid optic ganglion was injected into rabbits, the resulting sera did not inhibit squid OPAA, and did not give a positive ELISA. Control sera taken from the same rabbits prior to any injection (RS) did not inhibit the OPAAs. These results show another major difference between squid type OPAAs and the OPAAs from other sources, sometimes termed "Mazur type" OPAAs. PMID- 8216374 TI - Effects of temperature on the interaction of cisplatin and carboplatin with cellular DNA. AB - Increased levels of cisplatin (cDDP)- and carboplatin (CBDCA)-DNA adducts were detected in cDDP (10 microM)- and CBDCA (6 mM)-treated CC531 cells when the temperature was raised from 37 degrees to 43 degrees. In the case of cDDP, increased DNA adduct formation was already detectable at 38.5 degrees; additional temperature steps led to further increases in DNA modification. Increased CBDCA DNA adduct formation was observed only at temperatures higher than 40 degrees. In vitro studies on the interaction of CDDP and CBDCA with isolated salmon sperm DNA, however, demonstrated no significant differences in the DNA binding rate between 37 degrees and 43 degrees for cDDP and a minor effect for CBDCA only at 43 degrees, almost totally excluding a direct temperature effect on DNA platination in this temperature range. Furthermore, neither the stability of the formed platinum-DNA adducts nor the rate of adduct loss in CC531 cells was changed at higher temperatures. The observed difference in cellular adduct formation, however, could be related to increased uptake of cDDP and CBDCA into CC531 cells at higher temperatures. In the case of cDDP, a temperature shift from 37 degrees to 38.5 degrees resulted in a significantly higher intracellular platinum concentration (0.03 +/- 0.01 vs 0.071 +/- 0.021 micrograms platinum/10(6) cells, respectively); for CBDCA, temperatures > or = 41.5 degrees were needed to increase the platinum concentration significantly above 37 degree values (0.3 +/- 0.1 vs 0.6 +/- 0.1 micrograms platinum/10(6) cells, respectively). In addition, the increase in DNA adduct formation of cDDP and CBDCA at elevated temperatures was comparable with the increase in cDDP-DNA adducts after a cDDP concentration escalation at 37 degrees, indicating a concentration-dependent increase in cDDP-DNA adducts. It seems that heat affects primarily the cellular uptake of cDDP and CBDCA and not their covalent binding to DNA. PMID- 8216375 TI - Regulation of cardiac adenylyl cyclase by epidermal growth factor (EGF). Role of EGF receptor protein tyrosine kinase activity. AB - We have shown previously that the alpha subunit of the stimulatory GTP binding regulatory component of adenylyl cyclase (Gs alpha) mediates epidermal growth factor (EGF)-elicited stimulation of rat cardiac adenylyl cyclase (Nair et al., J Biol Chem 265: 21317-21322, 1990). Employing purified protein phosphotyrosine phosphatase, and benzylidene derivatives (tyrphostins: compounds 11 and 12) that selectively inhibit EGF receptor protein tyrosine kinase (EGFRK) activity, the role of EGFRK in EGF-mediated stimulation of cardiac adenylyl cyclase was investigated. The ability of the tyrphostins to inhibit the EGFRK activity in cardiac membranes was determined by monitoring tyrosine phosphorylation of either the 170 kDa protein or immunoprecipitated EGF receptor at 0 degrees and room temperature, respectively. Compounds 11 and 12, in a concentration-dependent manner, inhibited EGF receptor tyrosine kinase activity. In assays of adenylyl cyclase activity neither compound 11 nor compound 12 altered Gpp(NH)p- or isoproterenol-stimulated activity. However, both compounds, in a concentration dependent manner, attenuated the ability of EGF to stimulate adenylyl cyclase activity without altering specific binding of [125I]EGF to cardiac membranes. Similarly, protein phosphotyrosine phosphatase obliterated the ability of EGF, but not isoproterenol, to stimulate adenylyl cyclase. Thus, we conclude that protein tyrosine kinase activity of the EGF receptor is essential for the stimulation of cardiac adenylyl cyclase by EGF. PMID- 8216376 TI - Association of anti-58 kDa endoplasmic reticulum antibodies with halothane hepatitis. AB - We recently showed that when rats were administered the inhalation anesthetic halothane, a 58 kDa liver endoplasmic reticulum protein became covalently trifluoroacetylated by the trifluoroacetyl chloride metabolite of halothane. Although the 58 kDa protein showed 99% identity to that of the deduced amino acid sequence of a cDNA reported to correspond to phosphatidylinositol-specific phospholipase C-alpha, it did not have phosphatidylinositol-specific phospholipase C activity. It was concluded that the reported cDNA of phosphatidylinositol-specific phospholipase C-alpha actually encoded for the 58 kDa endoplasmic reticulum protein of unknown function. Other researchers have come to the same conclusion and have shown that the 58 kDa protein has protein disulfide-isomerase and protease activities. We now report that patients with halothane hepatitis have serum antibodies that react with both purified trifluoroacetylated and native rat liver 58 kDa proteins. These results suggest that when patients are exposed to halothane a human liver orthologue of the rat liver trifluoroacetylated-58 kDa protein is formed. In certain patients, this protein may become immunogenic and lead to the formation of specific antibodies and or specific T-cells, which may react with both trifluoroacetylated and native 58 kDa proteins, and ultimately be responsible, at least in part, for the hepatitis caused by halothane. PMID- 8216377 TI - SR2508 (etanidazole) pharmacokinetics and biochemical effects in tumor and normal tissues of scid mice bearing HT-29 human colon adenocarcinoma. AB - Several lines of evidence implicate glutathione (GSH) depletion and/or GSH transferase inhibition in the sensitizing action of nitroimidazoles to alkylating agents. To characterize this interaction, scid mice bearing subcutaneously implanted HT-29 colon tumor (0.75 to 1.25 cm diameter) were treated with SR2508 (2 g/kg, i.p.). At intervals following treatment, samples of blood, liver, spleen, kidney and central non-necrotic tumor core and tumor periphery were obtained and analyzed for SR2508 content by high-pressure liquid chromatography. Tissues were assayed spectrophotometrically for GSH and GSH transferase. SR2508 plasma pharmacokinetics in this model were similar to those described previously (t 1/2 beta = 5.83 hr). The volume of distribution of 0.32 L/kg suggests minimal tissue binding. In tumor periphery and core samples SR2508 levels peaked at 1 hr, and declined exponentially in parallel with plasma. During the terminal phase core SR2508 levels were 10-fold and tumor periphery levels 4.3-fold those of concurrent plasma concentrations. Consistent with these data, tumor GSH levels in both periphery and core fell below 30% of control at 4 hr, and remained depressed > 12 hr. Delayed recovery of GSH content of tumor tissue may explain in part the selectivity of SR2508 for tumor (oxic or hypoxic). GSH transferase activity in tumor was inhibited both at the center and periphery to 75 and 71% of control, respectively, and it appeared that recovery occurred more slowly in the hypoxic core. The mild degree of inhibition observed does not support an important role for inhibition of GSH transferase in sensitization by SR2508 in this tumor. The pronounced selective depletion of GSH in tumor supports the further development of SR2508 in the reversal of alkylating agent resistance. PMID- 8216378 TI - Effects of flavonoids on the release of reactive oxygen species by stimulated human neutrophils. Multivariate analysis of structure-activity relationships (SAR). AB - In the present study we measured the inhibition by 34 compounds, either flavonoids or related substances, of the release of reactive oxygen species by human neutrophils after stimulation by three agents: the bacterial peptide N fMetLeuPhe (FMLP), the protein kinase C activator phorbol myristate acetate (PMA) or opsonized zymosan (OZ), using two chemiluminescent probes, lucigenin or luminol in the presence or absence of horseradish peroxidase (HRP). The data matrix (34 x 7) was submitted to multivariate analysis: first, a correspondence factorial analysis to uncover levels of correlation among the biochemical parameters and the specificity of action of the test-compounds and second, a minimum spanning tree analysis that classified the chemical structures into a network describing both specificity and amplitude of the inhibition of the chemiluminescence response. The major conclusions of the analyses were: (a) opposition between inhibition of poly-morphonuclear leukocytes (PMNs) stimulated by FMLP and of PMNs stimulated by PMA or OZ implying that, for the molecules under study, there was a fundamental difference in the manner in which this inhibition occurred and, conversely, a difference in the nature of the stimulatory action of these activators. Molecules lacking hydroxyl groups on ring B, i.e. chrysin, chalcone, flavone and galangin, molecules glycosylated in position 7, i.e. hesperidin and naringin and ring B mono-hydroxylated molecules were, for the most part, at the origin of this dichotomy and might interfere with the membrane FMLP receptor; (b) a marked difference in chemiluminescence inhibition in the presence or absence of HRP that can be explained by the differential action of catechins compared to flavone and flavonol derivatives; (c) a similarity in biological profile between non-flavonoids such as chalcone and phloretin and low mean-activity flavonoids such as chrysin and galangin and between the non-flavonoid curcumin and the highly active flavonoid isorhamnetin; (d) a reaffirmation of the importance of ring A (C5,7) and ring B (C3',4') dihydroxylation, ring C (C3) hydroxylation, but also of the presence of a methoxy group on ring B in engendering high potency. This potency is generally decreased by C2-C3 saturation and by glycosylation. The most active molecules identified in this study provide valuable information for the selection of simpler molecules (e.g. metabolites accounting for the potency of orally administered flavonoids) for further structure-activity relationship (SAR) studies that could lead to the design of novel drugs or prodrugs. PMID- 8216379 TI - 5-Benzylbarbituric acid derivatives, potent and specific inhibitors of uridine phosphorylase. AB - 5-Benzylbarbituric acid derivatives were synthesized as a series of new, specific, and potent inhibitors of uridine phosphorylase. Among these, 5-(m benzyloxy)benzyl-1-[(2-hydroxyethoxy)methyl] barbituric acid (5 benzyloxybenzylbarbituric acid acyclonucleoside, BBBA) was found to be the most potent with Ki values of 1.1 +/- 0.2 and 2.6 +/- 0.3 nM with uridine phosphorylase from human and mouse livers, respectively. BBBA exhibited competitive inhibition with uridine phosphorylase from both human and mouse livers. The 5-benzylbarbituric acid derivatives are specific inhibitors of uridine phosphorylase, as they had no effect on thymidine phosphorylase (EC 2.4.2.4), thymidine kinase (EC 2.7.1.21), uridine-cytidine kinase (EC 2.7.1.48), orotate phosphoribosyltransferase (EC 2.4.2.10), orotidine 5'-monophosphate decarboxylase (EC 4.1.2.23), and dihydrouracil dehydrogenase (EC 1.3.1.2). These compounds are more potent, easier to synthesize, and have better water solubility than their uracil counterparts as inhibitors of uridine phosphorylase. Furthermore, the 5-benzylbarbituric acids were found to be better inhibitors of human uridine phosphorylase than the murine enzyme, whereas the reverse holds true for the 5-benzyluracil derivatives. The 5-benzylbarbituric acid derivatives have potential usefulness in the therapy of cancer and AIDS, as well as other pathological and physiological disorders. PMID- 8216380 TI - Determination of the magnitude and enantioselectivity of ligand binding to rat and rabbit serum albumins using immobilized-protein high performance liquid chromatography stationary phases. AB - Rat, rabbit and human serum albumins were immobilized on an HPLC stationary phase, and the resulting phases were tested for their abilities to determine the extent and enantioselectivity of ligand binding to the respective albumins. A series of achiral and chiral compounds were chromatographed on the phases including benzodiazepinones, non-steroidal anti-inflammatory drugs, amino acids, warfarin and leucovorin. The chromatographic retentions of the benzodiazepinones and one series of nonsteroidal anti-inflammatory agents were compared with protein binding data from ultrafiltration studies. The observed correlation factors (r) were consistently 0.999, indicating that the albumin phases can be used to determine the magnitude of binding to the respective proteins. The enantioselectivity was also investigated, and the results indicate that the stationary phases can be used to determine relative enantioselectivities and intraspecies differences in this stereoselectivity. For example, when R- and S warfarin were studied, R-warfarin was retained to a greater extent than S warfarin by the rabbit serum albumin-stationary phase, whereas the opposite enantioselectivity was found for the rat and human albumins. Binding interaction studies were also conducted on the rabbit and rat albumin stationary phases by sequentially adding increasing concentrations of octanoic acid to the chromatographic mobile phase. The octanoic acid reduced the retention of a series of non-steroidal anti-inflammatory agents, and the results of the experiments suggest that the interaction takes place at two or more sites on the albumin molecule and by anti-cooperative allosteric interactions and competitive displacement. The results of this study demonstrate that the immobilized serum albumin columns can be used to quantitate and probe ligand binding interactions. PMID- 8216381 TI - Synthesis rates of glutathione and activated sulphate (PAPS) and response to cysteine and acetaminophen administration in glutathione-depleted rat hepatocytes. AB - The effects of cysteine and acetaminophen (AA) on the synthesis rates of glutathione (GSH), adenosine 3'-phosphate 5'-phosphosulphate (PAPS, activated sulphate) and the AA metabolites, AA-GSH and AA-sulphate were studied in rat hepatocytes depleted of GSH by diethyl maleate (DEM). The synthesis rates were determined simultaneously by a previously described radioactive tracer method. Preincubation of the hepatocytes with 0.7 mM DEM for 30 min depleted GSH by 59% (P < 0.05) and PAPS by 28% (P < 0.05). Incubation with a toxic AA concentration resulted in GSH synthesis at a rate of 95 nmol/(10(6) cells.min) which increased to 281 nmol/(10(6) cells.min) (P = 0.05) after addition of cysteine. However, increased GSH synthesis was not followed by increased AA-GSH synthesis [4.7 vs 4.8 nmol/(10(6) cells.hr)]. Also, PAPS synthesis increased after cysteine administration [10.2 to 19.1 nmol/(10(6) cells.min)] (P < 0.05) without any change in AA-sulphate synthesis 18.5 vs 18.3 nmol/(10(6) cells.hr)]. Thus, in contrast to hepatocytes with normal GSH concentration, cysteine stimulated both GSH and PAPS synthesis rates in GSH-depleted rat hepatocytes incubated with a toxic AA concentration without stimulation of AA-GSH or AA-sulphate synthesis rates, indicating that the hepatoprotective effect of cysteine on AA toxicity is primarily due to stimulation of a GSH-mediated reduction of the reactive AA metabolite N-acetyl-p-benzoquinoneimine back to AA. PMID- 8216382 TI - Stereoselective glucuronidation of (R)- and (S)-naproxen by recombinant rat phenol UDP-glucuronosyltransferase (UGT1A1) and its human orthologue. AB - Recombinant rat phenol UDP-glucuronosyltransferase (UGT1A1) conjugates (R) naproxen at a much higher rate (> 17-fold) than its (S)-enantiomer, substantiating previous findings on stereoselective glucuronidation of racemic naproxen. In contrast, the recombinant human orthologue conjugated both enantiomers at equal rates. In line with high constitutive expression of UGT1A1 in extrahepatic tissues, a high R/S ratio of naproxen glucuronidation was found in rat testes, intestine, lung and kidney. The results demonstrate that (R) naproxen represents a stereoselective substrate of rat UGT1A1, but not of the human orthologous UGT1A1. PMID- 8216383 TI - A discontinuous luminometric assay for monoamine oxidase. AB - A simple, sensitive and convenient discontinuous luminometric assay for monoamine oxidase (MAO) is described. It is based on measurement of the light production from the peroxidase-catalysed chemiluminescent oxidation of 5-amino-2,3-dihydro 1,4-phthalazinedione (luminol) by the hydrogen peroxide produced in the MAO reaction. The procedure is suitable for use with a wide range of MAO substrates, although 5-hydroxytryptamine, adrenaline and noradrenaline are too readily oxidized by hydrogen peroxide to be used. A particular advantage of this procedure is that it is applicable to the oxidation of substrates which do not yield products, such as an aldehyde or free ammonia, which form the basis of several alternative substrate-independent assay procedures. The application of the procedure to assay the oxidation of benzylamine, tyramine and 2-n pentylaminoacetamide (milacemide) by a crude mitochondrial preparation from rat liver and purified ox liver MAO-B is demonstrated. PMID- 8216384 TI - The effects of long-term administration of 3-thia fatty acid, a peroxisome proliferator, to Morris 7800 C1 hepatoma cells. AB - Morris 7800 C1 hepatoma cells were grown in the presence of 80 microM tetradecylthioacetic acid (TTA), a peroxisome proliferator, for 1 year (long-term treated cells). The growth of the Morris 7800 C1 hepatoma cells was inhibited in cells treated with TTA for up to 8 days. Treatment of the cells with TTA for 1 year did not reduce growth further. The growth inhibition was easily reversed by insulin (0.4 microM). Peroxisomal acyl-CoA oxidase (ACO) (EC 1.3.99.3) activity was increased 5.5 times in cells treated with TTA for 3 days. In the cells treated with TTA for 1 year the ACO activity was increased only two times. A similar ACO mRNA half-life (two times the control) was found in cells treated with TTA for 1 year and for 3 days. This implies a loss of effect of TTA on the transcription rate of the ACO gene in long-term-treated cells. PMID- 8216385 TI - Behavioral effects of long-term exposure to magnetic fields in rats. AB - Male rats and pregnant and nonpregnant female rats of the Wistar strain were sham exposed or exposed to static (0.49 T) or to extremely low frequency (50 Hz) magnetic fields (0.018 T) 2 h per day for 20 consecutive days. Measures of irritability, exploratory activity, and locomotion were made in that order before and after the 4th, 10th, and 17th 2-h exposures. A reliable decrease in the irritability of rats after repeated exposure to a static or undulating field was found. No significant effects of treatment conditions on open-field behavior and locomotor activity were observed. Pregnancy had no influence on the behavioral end points. These results indicate that irritability of rats may be used as a simple behavioral indicant of mammalian sensitivity to magnetic fields. PMID- 8216386 TI - Rats avoid exposure to HVdc electric fields: a dose response study. AB - Rats, given the choice, avoid exposure to alternating current (ac) 60-Hz electric fields at intensities > or = 75 kV/m. This study investigated the generality of this behavior by studying the response of rats when exposed to high voltage direct current (HVdc) electric fields. Three hundred eighty male Long Evans rats were studied in 9 experiments with 40 rats per experiment and in one experiment with 20 rats to determine 1) if rats avoid exposure to HVdc electric fields of varying field strengths, and 2) if avoidance did occur, what role, if any, the concentration of air ions would have on the avoidance behavior. In all experiments a three-compartment glass shuttlebox was used; either the left or right compartment could be exposed to a combination of HVdc electric fields and air ions while the other compartment remained sham-exposed. The third, center compartment was a transition zone between exposure and sham-exposure. In each experiment, the rats were individually assessed in 1-h sessions where half of the rats (n = 20) had the choice to locomote between the two sides being exposed or sham-exposed, while the other half of the rats (n = 20) were sham-exposed regardless of their location, except in one experiment where there was no sham exposed group. The exposure levels for the first six experiments were 80, 55, 42.5, 30, -36, and -55 kV/m, respectively. The air ion concentration was constant at 1.4 x 10(6) ions/cc for the four positive exposure levels and -1.4 x 10(6) ions/cc for the two negative exposure levels. Rats having a choice between exposure and non-exposure relative to always sham-exposed control animals significantly reduced the amount of time spent on the exposed side at 80 kV/m (P < .002) as they did at both 55 and -55 kV/m (P < .005). No significant differences between groups were observed at 42.5, 30, or -36 kV/m. To determine what role the air ion concentration might have had on the avoidance behavior at field strengths of 55 kV/m or greater, four additional experiments were conducted. The HVdc exposure level was held constant at either -55 kV/m (for three experiments) or -55 kV/m (for 1 experiment) while the air ion concentration was varied between experiments at 2.5 x 10(5) ions/cc, 1.0 x 10(4) for two of the experiments and was below the measurement limit (< +/- 2 x 10(3) ions/cc) for the other two experiments at 55 and -55 kV/m.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8216387 TI - Pretreatment of rats with pulsed electromagnetic fields enhances regeneration of the sciatic nerve. AB - Regeneration of the sciatic nerve was studied in rats pretreated in a pulsed electromagnetic field (PEMF). The rats were exposed between a pair of Helmholtz coils at a pulse repetition rate of 2 pps at a field density of 60 or 300 microT. The PEMF treatment was then discontinued. After an interval of recovery, regeneration of the sciatic nerve was initiated by a crush lesion. Regeneration of sensory fibers was measured by the "pinch test" after an additional 3-6 days. A variety of PEMF pretreatments including 4 h/day for 1-4 days or exposure for 15 min/day during 2 days resulted in an increased regeneration distance, measured 3 days after the crush lesion. This effect could be demonstrated even after a 14 day recovery period. In contrast, pretreatment for 4 h/day for 2 days at 60 microT did not affect the regeneration distance. The results showed that PEMF pretreatment conditioned the rat sciatic nerve in a manner similar to that which occurs after a crush lesion, which indicates that PEMF affects the neuronal cell body. However, the mechanism of this effect remains obscure. PMID- 8216388 TI - Influence of weak static and 50 Hz magnetic fields on the redox activity of cytochrome-C oxidase. AB - The effects of static and 50 Hz magnetic fields on cytochrome-C oxidase activity were investigated in vitro by strictly controlled, simultaneous polarographic measurements of the enzyme's high- and low-affinity redox reaction. Cytochrome-C oxidase was isolated from beef heart. Control experiments were carried out in the ambient geomagnetic and 50 Hz magnetic fields at respective flux densities of 45 and 1.8 microT. The experimentally applied fields, static and time-varying, were generated by Helmholtz coils at flux densities between 50 microT and 100 mT. Exposures were timed to act either on the combined enzyme-substrate interchange or directly on the enzyme's electron and proton translocations. Significant changes as high as 90% of the overall cytochrome-C oxidase activity resulted during exposure (1) to a static magnetic field at 300 microT or 10 mT in the high affinity range, and (2) to a 50 Hz magnetic field at 10 or 50 mT in the low affinity range. No changes were observed at other flux densities. After exposure to a change-inducing, static or time-varying field, normal activity returned. PMID- 8216389 TI - In vivo studies of the effect of magnetic field exposure on ontogeny of choline acetyltransferase in the rat brain. AB - Developmental increases of the activity of choline acetyltransferase (ChAT) were examined in the brains of fetuses and offspring from parent rats continuously exposed to a 500 mG, 60 Hz circularly polarized (CP) magnetic field (MF) prior to pregnancy, and further, during pregnancy and lactation. In developing rats between 12 days and 20 days of embryogenesis that were housed in a control unit, i.e., nonexposed to MF, the specific activity of ChAT in whole brain specimens increased from 2.4% to 6.9% of adult activity, while specific activity of ChAT in rat brain specimens between 12 days of embryogenesis and 10 days of postpartum increased from 2.4% to 21.6% of adult activity. On the other hand, the specific activity of ChAT in whole brain specimens from rats under housed MF exposure conditions was found to increase from 2.6% to 6.7% of adult activity between 12 days and 20 days of embryogenesis and from 2.6% to 21.6% of adult activity between 12 days of embryogenesis and 10 days postpartum. Furthermore, the effect of the same test magnetic environment on the specific activity of ChAT in the brains of parental rats was examined in order to determine whether magnetic field exposure of parental rats might reflect onto the development of fetal brain. It was observed that continuous exposure of parental rats to a 500 mG, 60 Hz CP MF did not show any significant changes in the specific activity of ChAT in the septodiagonal band complex, dorsal and ventral hippocampus, striatum, and frontoparietal cerebral cortex, as compared with the same brain regions of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216390 TI - Studies on the possible biological effects of 50 Hz electric and/or magnetic fields: evaluation of some glycolytic enzymes, glycolytic flux, energy and oxido reductive potentials in human erythrocytes exposed in vitro to power frequency fields. AB - An attempt has been made to understand whether 50 Hz electric and magnetic fields (EMFs) are involved in producing bioeffects by exposing human erythrocytes in vitro. The study evaluated some key glycolytic enzymes, glucose consumption, lactate production, energy charge, 2,3-diphosphoglycerate, and reduced glutathione levels, all of which are biochemical parameters significant to erythrocyte function. Cells exposed to individual or superimposed EMFs have not shown any significant difference compared with the controls. PMID- 8216391 TI - Inpatient rheumatic disease units: are they worth it? PMID- 8216392 TI - Hepatitis C virus infection in type II mixed cryoglobulinemia. PMID- 8216393 TI - Synovial lymphocytes can indicate specific microbiologic causes of rheumatoid arthritis. PMID- 8216394 TI - Detection of intraarticular abnormalities in osteoarthritis of the knee. A pilot study comparing needle arthroscopy with standard arthroscopy. AB - OBJECTIVE: To determine whether intraarticular abnormalities in osteoarthritis (OA) of the knee can be detected as well by needle arthroscopy as by standard arthroscopy. METHODS: Needle arthroscopy followed by standard arthroscopy was performed on 10 patients with knee OA (diagnosed according to American College of Rheumatology criteria) whose symptoms were not entirely attributable to the OA and were therefore an indication for further evaluation. Each knee was assessed for abnormalities of the menisci, articular cartilage (6 sites), and synovium (6 sites). RESULTS: Evaluation of the 18 menisci visualized with both techniques yielded the same results: 6 abnormal and 12 normal. Among the 54 articular cartilage sites evaluable with both procedures, 16 were judged normal by both needle arthroscopy and standard arthroscopy. Of the 38 cartilage sites judged abnormal by standard arthroscopy, 34 (89%) were abnormal by needle arthroscopy. Both techniques indicated cartilage changes were the same at 42 (78%) of the 54 sites; changes at the other 12 sites were 1 grade higher by standard arthroscopy than by needle arthroscopy. Both needle arthroscopy and standard arthroscopy revealed 51 evaluable sites in the synovium. Of 34 areas judged abnormal by standard arthroscopy, 24 (71%) were also judged abnormal by needle arthroscopy; 17 areas were judged normal by both techniques. The 2 techniques assigned the same macroscopic score in 27 (53%) of 51 areas of the synovium, with a higher grade by standard arthroscopy in all but 1 of the other 16 areas. CONCLUSION: These pilot data suggest that in knee OA, needle arthroscopy can 1) accurately detect meniscal abnormalities, 2) detect cartilage abnormalities, but may underestimate the severity, and 3) detect most synovial abnormalities, but often underestimates the severity. Needle arthroscopy is a potentially valuable rheumatologic tool for the assessment of OA of the knee. PMID- 8216395 TI - Radiographic assessment of disease progression in rheumatoid arthritis patients enrolled in the cooperative systematic studies of the rheumatic diseases program randomized clinical trial of methotrexate, auranofin, or a combination of the two. AB - OBJECTIVE: To determine the radiographic progression of disease in rheumatoid arthritis (RA) patients from the Cooperative Systematic Studies of the Rheumatic Diseases clinical trial of auranofin (AUR) versus methotrexate (MTX) versus a combination of the two. METHODS: Baseline (week-0) and study-end (week-48) hand/wrist radiographs in 200 of the 211 patients who completed this multicenter trial (95%) were scored blindly by 2 readers for the presence of erosions and joint space narrowing (JSN). Both intraobserver reliability and interobserver reliability were 0.80 for erosions (P < or = 0.001); intraobserver reliability and interobserver reliability were both 0.75 for JSN (P < or = 0.001). RESULTS: Worsening erosion and JSN scores occurred in all 3 treatment groups, but the difference from baseline reached significance only in the AUR group. CONCLUSION: Clinical improvement has been clearly documented in all 3 treatment groups in this trial. Radiographic deterioration occurs in RA even when clinical features improve, but progression of disease as determined radiographically may be slowed by treatment with MTX. PMID- 8216396 TI - Effects of methotrexate on radiologic progression in juvenile rheumatoid arthritis. AB - OBJECTIVE: To assess the effects of methotrexate (MTX) therapy on radiologic progression in juvenile rheumatoid arthritis (JRA). METHODS: We evaluated serial wrist radiographs for carpal length in 23 JRA patients with bilateral wrist involvement, before and during MTX treatment. These carpal length measurements were compared with established norms for carpal length in a healthy pediatric population. RESULTS: Both clinical responders to MTX (17 of 23 patients) and nonresponders (6 of 23) had decreasing carpal length prior to initiation of the treatment. Eleven of the 17 clinical responders had improved carpal length after a mean of 2.5 years of MTX treatment. All 6 clinical nonresponders had progressive loss of carpal length. CONCLUSION: MTX treatment resulted in radiologic improvement, as measured by carpal length, in the majority of children with JRA who had a clinical response to MTX. PMID- 8216397 TI - Chimeric CD4 monoclonal antibody cM-T412 as a therapeutic approach to rheumatoid arthritis. AB - OBJECTIVE: To investigate the effects of chimeric CD4 monoclonal antibody cM-T412 treatment in patients with rheumatoid arthritis (RA). METHODS: Thirty-two RA patients received daily doses of 10, 50, or 100 mg of cM-T412 intravenously for 7 days. RESULTS: There was a sustained decrease in the number of CD4+ T lymphocytes in all patients. Those who received 50 mg and 100 mg of the antibody experienced significant reductions in disease activity. CONCLUSION: Treatment with cM-T412 appears to have a dose-dependent beneficial effect in RA patients. The clinical effects of cM-T412 are independent of the depressed numbers of circulating CD4+ T cells. PMID- 8216398 TI - HLA-linked susceptibility to rheumatoid arthritis. A study of forty-one multicase families from northern India. AB - OBJECTIVE: To analyze segregation of rheumatoid arthritis (RA) with HLA-DR4 and/or other alleles in multicase RA families and to compare the segregation patterns among affected and unaffected sibs. METHODS: Forty-one multicase families (22 multiplex and 19 simplex) of northern Indian origin were studied for HLA haplotype segregation. RESULTS: HLA haplotype sharing among affected sibs was observed more often than expected in families in which both parents were healthy (P < 0.05). RA cosegregated with a DR4 haplotype among offspring only in multiplex families in which both parents were unaffected (P < 0.05), while in simplex families, the disease segregated with DR4 only when the allele was from the affected DR4-heterozygous parent. In DR4-negative affected sib pairs, DR1, DR6, and DR10 were inherited from healthy parents more often than expected. CONCLUSION: Dissimilar modes of inheritance are seen among multiplex and simplex RA families. The results of segregation analysis are compatible with the hypothesis that an epitope, rather than an individual DR antigen(s), is responsible for increased risk for development of RA. PMID- 8216399 TI - Lupus and pregnancy studies. AB - OBJECTIVE: To examine factors prior to pregnancy in patients with systemic lupus erythematosus (SLE) that are prognostic for the occurrence of active disease during and shortly after pregnancy. METHODS: Case-control study of pregnant SLE patients and nonpregnant SLE controls, using logistic regression analyses to assess the role of prepregnancy disease activity as a prognostic factor for flare during pregnancy or the postpartum followup period. RESULTS: Lupus flares occurred frequently and in similar percentages of pregnant SLE patients and control SLE patients. Active lupus at study entry, both in control and in pregnant patients, was not predictive of flare. Inactive lupus at onset was not protective against flare in controls but was protective in pregnant lupus patients. CONCLUSION: Inactive disease at the onset of pregnancy in SLE provides optimum protection against the occurrence of flare during pregnancy. PMID- 8216400 TI - Predictors of psychosocial adjustment in systemic sclerosis. The influence of formal education level, functional ability, hardiness, uncertainty, and social support. AB - OBJECTIVE: To determine predictors of psychosocial adjustment in patients with systemic sclerosis (SSc). METHODS: We surveyed 94 patients with SSc. Age, sex, education level, marital status, work status, income, support group attendance, length of time since diagnosis, functional status, social support, illness related uncertainty, and hardiness were examined as potential predictors of psychosocial adjustment. The reliability and validity of the instruments used to measure these variables have been established. RESULTS: Only education level, functional ability, illness-related uncertainty, hardiness, and social support were predictive of psychosocial adjustment. Education level and functional ability explained 14% of the variance in psychosocial adjustment, while illness related uncertainty, hardiness, and social support increased the explained variance to 38%. CONCLUSION: Although patients with relatively poorer psychosocial adjustment to illness have lower formal education levels and more functional disability, the majority of the explained variance in psychosocial adjustment is ascribable to illness-related uncertainty, low level of hardiness, and less satisfaction with social support. PMID- 8216401 TI - Modulation of human T cell responses by nitric oxide and its derivative, S nitrosoglutathione. AB - OBJECTIVE: To examine the effects of nitric oxide (NO) and its more stable derivative, S-nitrosoglutathione (SNO-GSH), on the response of activated T lymphocytes. METHODS: The effects of NO and SNO-GSH on DNA synthesis, interleukin 2 (IL-2) production, IL-2 receptor expression, and cGMP accumulation were determined in phytohemagglutinin-activated peripheral blood mononuclear cells (PBMC) and spleen T cells. RESULTS: Nitric oxide (half-life [T1/2] < 15 seconds) did not inhibit T cell proliferation. However, the derivative SNO-GSH (25 microM) (T1/2 > 2 hours) inhibited DNA synthesis by a mean +/- SD of 65 +/- 19.6% (P < 0.001) in PBMC and 75 +/- 15% (P < 0.001) in spleen cells. Macrophage depletion of PBMC did not abrogate the inhibition. SNO-GSH had no effect on IL-2 production or IL-2 receptor expression. NO (25 microM) increased the cGMP content of PBMC (0.65 +/- 0.15 pmoles/10(6) cells; P < 0.04), as did SNO-GSH (25 microM) in both PBMC (3.8 +/- 1; P < 0.001) and spleen T cells (5.2 +/- 1.2; P < 0.001). Methylene blue and hemoglobin, which are NO inhibitors, inhibited SNO-GSH-induced cGMP accumulation (P < 0.001). CONCLUSION: SNO-GSH inhibits T cell DNA synthesis independently of IL-2 production and in association with cGMP accumulation via a NO-dependent mechanism. We suggest that NO and its S-nitrosothiol derivatives may act as endogenous inhibitors of T cell-mediated inflammation. PMID- 8216402 TI - Detection of human T lymphotropic virus type I tax gene in salivary gland epithelium from two patients with Sjogren's syndrome. AB - OBJECTIVE: To investigate whether human T lymphotropic virus type I (HTLV-I) could be involved in the pathogenesis of Sjogren's syndrome (SS). METHODS: Labial salivary gland (LSG) biopsy specimens from 9 patients with SS (4 with primary SS and 5 with SS secondary to rheumatoid arthritis) and 9 controls were studied for the presence of the tax gene of HTLV-I using in situ hybridization, and for the presence of tax, gag, pol, and env genes of HTLV-I using the polymerase chain reaction (PCR). Testing for antibodies to HTLV-I and examination of lymphocytes on blood smears were performed to determine whether systemic viral infection was present. RESULTS: Using in situ hybridization and PCR, we detected the tax gene, but not the gag, pol, or env genes, of HTLV-I in LSG sections from 2 of 9 patients with SS and from none of the control subjects. Tax DNA was present mostly in nuclei of epithelial cells, but also in some lymphoid cells. Serum of the 2 affected patients did not contain antibodies to HTLV-I. In 1 patient, examination of blood smears revealed rare convoluted lymphocytes, sometimes with the appearance of "flower cells," as observed in the blood of HTLV-I-infected patients. CONCLUSION: None of the known endogenous retroviral sequences is homologous to the tax gene. Thus, we suggest that HTLV-I (or another related retrovirus) can infect salivary epithelium. Transactivation properties of the tax protein could be implicated in the pathogenesis of SS. Alternatively, viral infection could cause de novo expression of HLA-DR antigens and favor the presentation of antigens by epithelial cells, leading, in some genetically predetermined subjects, to lymphoid infiltration of the gland. PMID- 8216403 TI - A quantitative assessment of limited joint mobility in patients with diabetes. Goniometric analysis of upper extremity passive range of motion. AB - OBJECTIVE: The syndrome of limited joint mobility is a common but not widely recognized musculoskeletal complication of diabetes. The purpose of this study was to further characterize this syndrome using quantitative goniometric measures. METHODS: Cross-sectional analysis of a sample population was performed to establish the prevalence, location, and severity of limited joint mobility and to determine its relationship to extraarticular manifestations and complications of diabetes. Passive range of motion of both upper extremities was measured by goniometry in 70 adult patients with insulin-dependent diabetes mellitus and 70 nondiabetic controls who were group-matched for age, sex, and general activity level. Joint mobility was assessed by both individual joint motions and a composite scoring technique. RESULTS: Analysis of individual joints and composite scores revealed significant differences between dominant and nondominant extremities in both the control and the diabetic groups. Diabetic patients were generally less flexible than nondiabetic subjects throughout the arm, especially in shoulder and finger joints. In the full study population, multivariate analysis revealed that advanced age, male sex, and the presence of diabetes were associated with decreased passive range of motion for a majority of joints (P < 0.05). In the diabetes group, passive range of motion was significantly correlated (P < 0.05) with age, sex, duration of diabetes, and to a variable extent, glucose control, but was not correlated with the presence of clinically significant neuropathy, retinopathy, nephropathy, or peripheral vascular disease, with activity level, or with hand dominance. Stepwise regression analysis failed to identify single key joint motion(s) to serve as possible screening tests in predicting generalized limited joint mobility of the upper extremity. Finally, the effect of limb usage on range of motion in flexion may differ in diabetic and nondiabetic subjects. CONCLUSION: Limited joint mobility is a generalized phenomenon occurring throughout the upper extremities of many diabetic patients. It is significantly related to age, sex, and to a variable extent duration of diabetes and glucose control. It is not related to the standard complications of diabetes as defined in this study. PMID- 8216404 TI - In vitro release of prostaglandins and leukotrienes from synovial tissue, cartilage, and bone in degenerative joint diseases. AB - OBJECTIVE: To determine the major source of eicosanoid release in arthritic joint tissues and to examine the modulation of this release by indomethacin and diclofenac. METHODS: Release of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, leukotriene B4 (LTB4), and LTC4 was measured in supernatants of synovial tissue, cartilage, and bone incubates from patients with osteoarthritis, active rheumatoid arthritis (RA), inactive RA, and pseudogout. Radioimmunoassay (RIA) was used to determine the levels of the eicosanoids. RESULTS: Addition of the divalent cation ionophore A23187 resulted in significant release of all eicosanoids measured from synovial tissue, but not from cartilage, cortical bone, or cancellous bone. PG release was significantly inhibited by the addition of indomethacin or diclofenac at either 10(-5) moles/liter or 10(-7) moles/liter. The amount of LTC4 released from cartilage and bone was only slightly above the detection limit of the RIA, whereas large amounts were released from synovial tissue. Neither indomethacin nor diclofenac had an effect on LTC4 release. LTC4 release from synovial tissue of patients with inactive RA was significantly decreased in comparison with the levels from synovial tissue of patients with the other joint diseases. There was no significant difference in PG release among patients in the various disease groups. CONCLUSION: Synovial tissue appears to be the major source of eicosanoids in synovial fluid. Indomethacin and diclofenac inhibit the release of PG, but not LT, from various joint tissues. PMID- 8216405 TI - A longitudinal study of subchondral plate and trabecular bone in cruciate deficient dogs with osteoarthritis followed up for 54 months. AB - OBJECTIVE: To evaluate the sequence of changes in articular cartilage, trabecular bone, and subchondral plate in dogs with osteoarthritis (OA), 3 months, 18 months, and 54 months after anterior cruciate ligament transection (ACLT). METHODS: Specimens of the medial tibial plateau were analyzed with microscopic computed tomography (micro-CT) at a resolution of 60 microns, and biochemical and morphologic changes in the femoral articular cartilage were assessed. RESULTS: At 3 months and 18 months after ACLT, the articular cartilage in the unstable knee showed histologic changes typical of early OA and increased water content and uronic acid concentration; by 54 months, full-thickness ulceration had developed. Micro-CT analysis showed a loss of trabecular bone in the unstable knee, compared with the contralateral knee, at all time points. At both 18 and 54 months, the differences in trabecular thickness and surface-to-volume ratio were greater than at 3 months. Although the mean subchondral plate thickness, especially in the medial aspect of the medial tibial plateau, was greater in the OA knee than in the contralateral knee 18 months and 54 months after ACLT, these differences were not statistically significant; however, the difference was significantly greater at 54 months than at 3 months. CONCLUSION: Thickening of the subchondral bone is not required for the development of cartilage changes of OA in this model. The bony changes that develop after ACLT, however, could result in abnormal transmission of stress to the overlying cartilage and thereby contribute to the progression of cartilage degeneration. PMID- 8216406 TI - Myopathy with mitochondrial alterations in patients with primary biliary cirrhosis and antimitochondrial antibodies. AB - OBJECTIVE: To describe a syndrome of severe progressive myopathy, cardiomyopathy, and gastrointestinal dysmotility in 2 patients with asymptomatic primary biliary cirrhosis (PBC) and circulating antimitochondrial autoantibodies, and to review pertinent literature concerning this syndrome. METHODS: Clinical, electrophysiologic, serologic, and pathologic studies of the 2 affected patients were conducted. RESULTS: Skeletal muscle involvement was manifested by progressive weakness of the proximal muscles, marked diaphragmatic dysfunction with consequent hypoventilation and respiratory failure, and moderately elevated levels of muscle-associated enzymes. Serum from both patients contained antimitochondrial antibodies that reacted with components of the mitochondrial keto acid dehydrogenase enzyme complex. Results of electromyography were consistent with a myopathic process. The microscopic and ultrastructural changes in the skeletal muscles were distinct from those of typical myositis, and were notable for striking subsarcolemmal aggregation of abnormal mitochondria in the absence of significant inflammation. CONCLUSION: Severe skeletal muscle, cardiac, and gastrointestinal pathology with abnormalities of the muscle mitochondria develops in a subset of patients with mild PBC and antimitochondrial antibodies. The pathogenesis of this syndrome is unclear, but may be related to the presence of the antimitochondrial autoantibodies. PMID- 8216407 TI - Calcific tendinitis in the proximal thigh. AB - Calcific tendinitis of the proximal thigh is a benign entity that may cause significant pain. It must be distinguished from chronic or malignant disorders, such as arthritis, infection, and soft tissue/cortical neoplasms. Although it may be self-limited, some patients will benefit from medical intervention. In such cases, we recommend computed tomography-guided percutaneous steroid injection. Herein we describe the clinical and radiographic features of calcific tendinitis of the proximal thigh in 5 patients. PMID- 8216408 TI - Photodermatitis in a 6-year-old child. PMID- 8216409 TI - Rheumatic disorders during Operation Desert Storm. PMID- 8216410 TI - Persistent eosinophilia in 2 patients with eosinophilia-myalgia syndrome. PMID- 8216411 TI - Discordance for autoimmunity in monozygotic twins. Are "identical" twins really identical? PMID- 8216412 TI - Functional imaging in systemic lupus erythematosus: an accurate indicator of central nervous system involvement? PMID- 8216413 TI - Comparison of naproxen and acetaminophen in a two-year study of treatment of osteoarthritis of the knee. AB - OBJECTIVE: To compare the relative safety and efficacy of naproxen and acetaminophen in the treatment of osteoarthritis (OA) of the knee. The major outcome measures were radiographic progression and withdrawal from the trial due to lack of efficacy. METHODS: One hundred seventy-eight patients with OA of the knee were enrolled in a 2-year prospective, controlled, double-blind multicenter trial and were randomly assigned to receive acetaminophen (ACT) or naproxen (NPX) treatment. RESULTS: After 6 weeks of treatment, modest improvement in pain on motion and in physician's global assessment was seen in both the ACT and the NPX groups, and the NPX group also had modest improvement in pain at rest and in 50 foot walk time. Sixty-two patients completed the 2-year study. Among these patients, radiographic progression was similar in the 2 treatment groups. Withdrawal from the trial due to lack of drug efficacy was slightly more frequent among patients in the ACT group (22% versus 16%), but withdrawal due to adverse drug effects was slightly more common in the NPX group (23% versus 18%). CONCLUSION: The efficacy of ACT treatment and NPX treatment was similar, although it was slightly better for NPX. The toxicity rate was slightly lower with ACT. However, the high rate of withdrawal in both treatment groups suggests that neither is satisfactory for the treatment of OA. PMID- 8216414 TI - Effect of piroxicam on gait in patients with osteoarthritis of the knee. AB - OBJECTIVE: To determine whether the use of a nonsteroidal antiinflammatory drug (NSAID) in patients with painful osteoarthritis (OA) of the knee would result in alterations in specific biomechanical parameters of gait. METHODS: Eighteen patients with symptomatic knee OA and varus knee deformity underwent initial clinical evaluation for pain and activities of daily living, and assessment of parameters of gait utilizing a well-described computerized system. All patients were then treated with piroxicam at 20 mg once daily, and clinical and gait analyses were repeated after 4 weeks. RESULTS: Fifteen of the 18 patients studied had a significant increase in the knee adduction moment after treatment. In the group as a whole there was a significant increase in knee adduction moment (mean percent body weight times height [%BWTH] 4.11 pretreatment versus 4.57 after 4 weeks of treatment; P < 0.01) and maximum quadriceps moment (mean %BWTH 2.13 pretreatment, 2.62 posttreatment; P < 0.01), as well as changes in other gait parameters that might be expected to be altered as a result of relief of pain. Sixteen of 18 patients experienced symptomatic relief, with a significant reduction in pain in the group as a whole after 4 weeks (P < 0.001). CONCLUSION: NSAID treatment in patients with knee OA results in a reduction in symptomatic pain and an increase in loading of the knee. Whether the increased loading is due to the analgesic effects of the treatment is unknown, but if so, the development of agents capable of relieving pain while reducing loads at the knee may be desirable. PMID- 8216415 TI - The structure of aggrecan fragments in human synovial fluid. Evidence that aggrecanase mediates cartilage degradation in inflammatory joint disease, joint injury, and osteoarthritis. AB - OBJECTIVE: To determine the proteolytic fragmentation patterns and N-terminal sequence of aggrecan fragments in human synovial fluid from patients with inflammatory arthritides, joint injury, or osteoarthritis (OA). METHODS: Knee synovial fluid was obtained from patients with joint injury, OA, acute pyrophosphate arthritis (pseudogout), reactive arthritis, psoriatic arthritis, or juvenile rheumatoid arthritis. Chondroitin sulfate-substituted aggrecan fragments present in the fluid were purified by cesium chloride gradient centrifugation and enzymatically deglycosylated. Core protein species were determined by N-terminal analysis and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) with electroblotting and detection with monoclonal antibody 3B3. RESULTS: Samples from patients with joint injury, OA, and inflammatory joint disease all showed a similar 3-band pattern, with core sizes of approximately 200 kd, 170 kd, and 135 kd. In all samples, diffuse immunoreactive products were also seen, with an apparent size of > 250 kd. N-terminal analysis of core preparations of all samples showed a consistent single predominant sequence, beginning at alanine 374 of the human aggrecan core protein. CONCLUSION: The aggrecan fragments present in joint fluids from patients with various inflammatory arthritides, joint injury, or OA result from a predominant cleavage of the human aggrecan core protein at the glutamate 373-alanine 374 bond within the interglobular domain, between the G1 and G2 domains. The consistent pattern of fragments seen on SDS-PAGE and the single predominant N-terminal sequence suggest a common degradative mechanism of aggrecan in these different joint conditions. The identity of the proteolytic agent (aggrecanase), however, remains unknown. These results appear to have important implications with regard to the development of therapies to protect cartilage from degradation in patients with joint disease. PMID- 8216416 TI - DAB486IL-2 fusion toxin in refractory rheumatoid arthritis. AB - OBJECTIVE: To evaluate the safety and antiarthritic effects of DAB486IL-2. This agent is a fusion toxin and the product of a synthetic gene, engineered by replacing the codons for the receptor-binding domain of diphtheria toxin (DT) with the codons for human interleukin-2 (IL-2). DAB486IL-2 targets cells expressing the 2-chain, high-affinity form of the IL-2 receptor (IL-2R), and achieves selective diphtheria toxin-mediated cytotoxicity of activated T cells by inhibition of protein synthesis. METHODS: Nineteen patients with rheumatoid arthritis (RA) that had been refractory to methotrexate participated in an open label, phase I/II trial evaluating 3 dose levels of intravenous DAB486IL-2 given for 5 or 7 consecutive days. Thirteen patients received additional courses, at higher doses if the original response had been inadequate or at an equivalent dose if the original course produced a response, for a total of 38 courses. Arthritis response was assessed at 28 days, with biweekly followup of patients with substantial response (> or = 50% improved) or meaningful response (> or = 25% improved). Laboratory monitoring included measurement of CD4+ cells and circulating shed IL-2R. RESULTS: Nine of 19 patients treated with high- or medium dose DAB486IL-2 had a substantial or meaningful response after 1 or 2 treatment courses. No significant responses occurred with the low-dose regimen. Clinical benefit was rapid, with full effect noted by 14 days following completion of infusions. Antibodies to DT developed in all patients, or levels of preexisting antibodies were boosted. Adverse effects included transient elevation of transaminase levels (55% of the patients), fever (40%), nausea or anorexia (30%), hypersensitivity (6%), and thrombocytopenia (5%). Repeat courses were associated with less transaminase elevation and were clinically effective despite induction of anti-DT antibodies. CONCLUSION: The results of this open trial provide preliminary evidence for a potential therapeutic effect of DAB486IL-2 in RA, with an acceptable safety profile. Reversible transaminase elevations limit escalation of the dosage beyond 0.1 mg/kg/day. A controlled study of DAB486IL-2 is required to determine the efficacy of this high-affinity IL-2R-targeted fusion toxin in the treatment of RA. PMID- 8216417 TI - Biased T cell receptor V gene usage in rheumatoid arthritis. Oligoclonal expansion of T cells expressing V alpha 2 genes in synovial fluid but not in peripheral blood. AB - OBJECTIVE: To analyze the T cell receptor (TCR) variable (V) region gene usage in the rheumatoid joint. METHODS: Monoclonal antibodies (MAb) were used to determine the prevalence of selected V elements on T cells in synovial fluid (SF) from rheumatoid arthritis (RA) patients and in peripheral blood (PB) from RA patients and normal controls. V alpha 2-positive PB and SF T cells from 1 patient were cloned by immediate limiting-dilution and analyzed by restriction mapping. RESULTS: In 9 of 14 RA patients, SF was enriched in at least 1 of the selected V elements, compared with PB. TCR genes of the V alpha 2 family were the most frequently overrepresented in the SF (4 patients). The expanded V alpha 2 positive cells were oligoclonal in SF but heterogeneic in PB. CONCLUSION: Our data showing biased and clonally restricted TCR elements in the rheumatoid joint indicate major histocompatibility complex-restricted antigen recognition, rather than a "superantigen," in the pathogenesis of RA. PMID- 8216418 TI - Reduction of leukocyte and interleukin-1 beta concentrations in the synovial fluid of rheumatoid arthritis patients treated with methotrexate. AB - OBJECTIVE: To examine the effect of methotrexate (MTX) on the numbers of leukocytes in the peripheral blood (PB) and synovial fluid (SF) of patients with active rheumatoid arthritis (RA). METHODS: Twelve patients were treated with MTX; 5 patients not taking MTX served as controls. Samples of PB and SF were collected at 0, 1, 4, and 8 weeks of the study. Disease activity was scored, and total leukocytes, neutrophils, lymphocytes, and CD4+, CD8+, DR+, and CD25+ lymphocyte subsets were analyzed in PB and SF. Interleukin-1 beta (IL-1 beta) concentrations in SF were determined. RESULTS: Patients treated with MTX showed significant clinical improvement. No change in PB leukocytes or lymphocyte subsets was observed in either patient group over the 8-week study period. In contrast, the number of leukocytes, the number and proportion of neutrophils, and the concentration of IL-1 beta in the SF of patients treated with MTX were reduced. In addition, in MTX-treated patients, there was an appreciable decrease in SF CD8+ lymphocytes, but not CD4+, DR+, or CD25+ lymphocytes. CONCLUSION: These findings suggest that in RA, MTX acts, at least in part, by reducing the migration of leukocytes into the inflamed synovium. Local reduction of IL-1 beta secretion may contribute to this effect. PMID- 8216419 TI - Single-photon-emission computed tomography analysis of cerebral blood flow in the evaluation of central nervous system involvement in patients with systemic lupus erythematosus. AB - OBJECTIVE: Single-photon-emission computed tomography (SPECT) scanning was used to detect potential central nervous system (CNS) involvement in patients with systemic lupus erythematosus (SLE), by determining cerebral blood flow abnormalities. METHODS: SPECT scans were performed on 35 SLE patients, grouped into 3 categories: those without neuropsychiatric symptoms (n = 10), those with definite neurologic or psychiatric disorders (n = 10), and those with mild symptoms such as headache or memory disturbances (n = 15). SPECT scan features were classified as normal or as focal or diffuse defects in uptake. RESULTS: SPECT findings were normal in 9 of the 10 patients without CNS symptoms, and abnormal in 9 of the 10 patients with overt neuropsychiatric disease (with motor or sensory deficits). Interestingly, only 4 of the 15 patients (26.7%) with mild symptoms suggestive of CNS disease had normal SPECT findings; the 11 remaining patients showed focal (53.3%) or diffuse (20%) uptake defects. An association between SPECT findings and disease duration was also observed, but there was no correlation of SPECT results with overall disease activity, serologic findings, or medications used. CONCLUSION: Our data suggest that in a substantial proportion of patients, SPECT analysis may provide additional information on potential CNS involvement, and may therefore be useful in therapeutic decision making and disease monitoring in order to prevent CNS damage. PMID- 8216420 TI - Identification of mothers at risk for congenital heart block and other neonatal lupus syndromes in their children. Comparison of enzyme-linked immunosorbent assay and immunoblot for measurement of anti-SS-A/Ro and anti-SS-B/La antibodies. AB - OBJECTIVE: To identify the fine specificity patterns of maternal anti-SS-A/Ro and anti-SS-B/La antibodies that are associated with the birth of a child with transient or permanent manifestations of neonatal lupus syndromes, and to suggest a predictor algorithm for use in counseling. METHODS: Sera were obtained from 4 groups of mothers: 57 whose children had congenital heart block, 12 whose children had transient dermatologic or hepatic manifestations of neonatal lupus but no detectable cardiac involvement, 152 with systemic lupus erythematosus and related autoimmune diseases, who gave birth to healthy infants, and 30 with autoimmune diseases whose pregnancy resulted in miscarriage, fetal death, or early postpartum death unrelated to neonatal lupus. Antibodies to SS-A/Ro and SS B/La were assessed by enzyme-linked immunosorbent assay (ELISA) and by sodium dodecyl sulfate (SDS)-immunoblot. RESULTS: Anti-SS-A/Ro antibodies were identified by ELISA in 100%, 91%, 47%, and 43% of the mothers of infants with heart block, with transient neonatal lupus, healthy infants, and fetal death, respectively. High titers of anti-SS-A/Ro antibodies were present more often in mothers of children with cardiac disease or transient neonatal lupus than in either of the other 2 groups. Maternal antibodies to SS-B/La were detected by ELISA in 76% of the heart block group, 73% of the cutaneous neonatal lupus group, 15% of the group with healthy children, and 7% of the fetal death group. On SDS immunoblot, sera from 91% of the heart block group mothers who had antibodies to SS-A/Ro but not to SS-B/La recognized at least 1 SS-A/Ro antigen, with significantly greater reactivity against the 52-kd component. In contrast, only 62% of the anti-SS-A/Ro positive, anti-SS-B/La negative responders in the healthy group recognized the 52-kd and/or the 60-kd component. Although there was no profile of anti-SS-A/Ro response unique to the mothers of children with heart block or cutaneous manifestations of neonatal lupus, only 1% of the healthy infants were born to mothers with antibodies directed to both the 52-kd SS-A/Ro and 48-kd SS-B/La antigens and not to the 60-kd SS-A/Ro antigen. CONCLUSION: Women with antibodies to both SS-A/Ro and SS-B/La have an increased risk of giving birth to children with neonatal lupus, especially if the anti-SS-A/Ro response identifies the 52-kd component on SDS-immunoblot. Women whose sera contain only anti-SS-A/Ro antibodies in low titer and only recognize determinants that are altered by conditions of SDS-immunoblot have a low risk for giving birth to a child with neonatal lupus. Specific antibody profiles do not distinguish among the manifestations of the neonatal lupus syndromes. PMID- 8216421 TI - Changes in the proteins coating monosodium urate crystals during active and subsiding inflammation. Immunogold studies of synovial fluid from patients with gout and of fluid obtained using the rat subcutaneous air pouch model. AB - OBJECTIVE: In this in vivo study, we investigated changes in the proteins that coat monosodium urate (MSU) crystals in human synovial fluid samples and rat air pouch fluid samples obtained sequentially during periods of active and resolving inflammation, in order to evaluate whether in vivo findings are consistent with hypotheses on roles of protein coating based on in vitro findings. METHODS: Crystals from patients with gout were isolated from joint fluids with acute inflammation, and subsequently from the same joints at the time inflammation was resolving. Crystals were also obtained using the rat subcutaneous air pouch model. Immunogold was used to label proteins coating MSU crystals, for light microscopy (LM) and transmission electron microscopy (TEM) studies. RESULTS: Dense immunogold-silver labeling for IgG was observed under LM on crystals from fluid with acute inflammation, whereas other proteins (apolipoproteins [Apo], fibronectin, fibrinogen, albumin) were not labeled significantly. Apo B became strongly positive on crystals as the inflammation subsided, whereas other proteins were only weakly positive and IgG became absent or weakly positive. Quantitative TEM evaluation confirmed the LM observations. CONCLUSION: This study provides the first in vivo evidence supporting the notion derived from previous in vitro studies that proteins coating MSU crystals change as inflammation evolves. Protein coatings may play an important role in the self-limited nature of gouty inflammation. IgG coating MSU crystals may enhance the inflammation. As the inflammation subsides, Apo B could displace the IgG by competitively coating sites on crystals and could contribute in part to the resolution of the acute gouty arthritis. PMID- 8216422 TI - Correlation of interleukin-6 production and disease activity in polymyalgia rheumatica and giant cell arteritis. AB - OBJECTIVE: To explore the role of proinflammatory cytokines in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR), two clinically related syndromes characterized by an intense acute-phase reaction. In particular, to determine plasma concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) and to correlate changes in plasma IL-6 levels with clinical symptoms during corticosteroid therapy. METHODS: IL-6 and TNF alpha concentrations were determined in plasma samples from patients with untreated PMR or GCA, and plasma IL-6 levels were monitored in patients receiving long-term therapy (14 months) with corticosteroids. To identify IL-6-producing cells, the polymerase chain reaction was used to detect IL-6 messenger RNA. In vitro production of IL-6 and IL-2 by peripheral blood mononuclear cells (PBMC) from treated and untreated patients was quantified using IL-6- and IL-2-specific bioassay systems. RESULTS: IL-6 concentrations were increased in PMR and GCA patients, whereas TNF alpha concentrations were similar to those in normal donors. Administration of corticosteroids rapidly reduced the levels of circulating IL-6 but did not correct the underlying mechanism inducing the increased IL-6 production. In individual patients, changes in plasma IL-6 levels and clinical manifestations during prolonged therapy were closely correlated. Short-term withdrawal of corticosteroids, even after several months of treatment, was followed by an immediate increase in plasma IL-6 concentrations. To identify the cellular source of plasma IL-6, PBMC from treated and untreated patients with PMR or GCA were analyzed for their ability to secrete IL-6 and the T cell specific cytokine IL-2. Polyclonal T cell stimulation caused a rapid release of IL-6, which was shown to be derived exclusively from CD14+ cells. CONCLUSION: Increased production of IL-6, but not TNF alpha, is a characteristic finding in patients with PMR or GCA. Corticosteroids rapidly suppress IL-6 production but do not correct the underlying mechanism inducing the increased IL-6 production. The close correlation of plasma IL-6 concentrations with clinical symptoms suggests a direct contribution of this cytokine to the disease manifestations and presents the possibility that monitoring IL-6 levels would be useful in making decisions on adjustment of corticosteroid dosage in individual patients. PMID- 8216423 TI - Synergistic effect of interleukin-1 beta and tumor necrosis factor alpha on interleukin-8 gene expression in synovial fibroblasts. Evidence that interleukin 8 is the major neutrophil-activating chemokine released in response to monokine activation. AB - OBJECTIVE: To investigate both the involvement of chemokines in general and the relative importance of specific chemokines in rheumatoid arthritis (RA), we characterized the effect of the monokines tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) on the synthesis of neutrophil-activating factors by synovial fibroblasts isolated from the joints of patients with RA. METHODS: Neutrophil-stimulating activity was assessed by determining intracellular calcium mobilization. IL-8 synthesis and secretion was assessed by specific enzyme-linked immunosorbent assay, and IL-8 messenger RNA (mRNA) levels were determined by Northern blot. RESULTS: Treatment of synovial fibroblasts with IL-1 beta and TNF alpha resulted in the production of an activity which induced intracellular calcium mobilization in peripheral blood neutrophils. The 2 monokines combined had a synergistic effect on the release of the neutrophil stimulating activity. The effect of the 2 monokines required gene transcription and translation, and closely mimicked the pattern of IL-8 secretion induced in these cells by the monokines. We confirmed that the majority of the neutrophil stimulating activity was IL-8 by 3 different approaches: cross-desensitization experiments with IL-8, melanoma growth-stimulatory activity, and neutrophil activating peptide 2, stimulation of calcium mobilization in cells transfected with the IL-8 receptor complementary DNA, and inhibition of the activity following pretreatment of the supernatants with an anti-IL-8 antibody. TNF alpha and IL-1 beta induced a time- and dose-dependent release of immunoreactive IL-8. A synergistic effect of TNF alpha and IL-1 beta was also observed for both IL-8 production and accumulation of IL-8 mRNA. CONCLUSION: These results indicate that the monokines TNF alpha and IL-1 beta synergistically activate IL-8 expression and protein secretion by synovial fibroblasts, and that under these conditions, IL-8 appears to be the major neutrophil-activating factor released. PMID- 8216424 TI - The effect of an interleukin-1 receptor antagonist protein on type II collagen induced arthritis and antigen-induced arthritis in mice. AB - OBJECTIVE: To investigate the anti-arthritic effect of recombinant human interleukin-1 receptor antagonist protein (IRAP) in two experimental models of arthritis. METHODS: Recombinant IRAP was administered daily to mice with type II collagen-induced arthritis (CIA) or with antigen-induced arthritis (AIA) provoked by methylated bovine serum albumin (mBSA). Disease incidence and severity were assessed by a clinical index and histologic features. Serum antibody to type II collagen, spleen cell proliferation to mBSA, and anti-IRAP antibodies were measured as indices of immune function. RESULTS: IRAP reduced the incidence and delayed the onset of CIA and suppressed the antibody response to type II collagen. In contrast, IRAP did not affect the pathogenesis of AIA and had no effect on either humoral or cellular immune responses to mBSA in arthritic mice. CONCLUSION: These observations suggest that interleukin-1 may play a prominent role in the development of some, but not all, forms of arthritis. PMID- 8216425 TI - Nucleotide sequence analysis of the VL and VH domains of five human IgM directed to lamin B. Evidence for an antigen-driven process in the generation of human autoantibodies to lamin B. AB - OBJECTIVE: To gain insight into the genetic origin of human antilamin autoantibodies, we determined the nucleotide sequence of the light and heavy chain variable region (VL and VH) domains of 5 IgM antibodies directed to lamin B. These antibodies represent a distinct subset of antinuclear antibodies, and their presence is associated with a particular lupus-like syndrome. METHODS: We derived and cloned lymphoblastoid cell lines from peripheral blood B cells of 3 patients, selected anti-lamin B-producing subclones, and sequenced the messenger RNA coding for Ig heavy and light chains. RESULTS: We isolated 2 subclones (1 IgM kappa, 1 IgM lambda) from one patient (FUR) and 2 subclones (both IgM lambda) from another (HER). In contrast, all 8 lines derived from B cells isolated from the third patient (BEN) synthesized identical anti-lamin B IgM kappa antibodies: All VL and VH domains from these 5 IgM were encoded by different VL or VH genes. DH regions were all different, and there was no restriction in the use of JL or JH segments. Analysis of the nucleotide sequence of the VL domains allowed the identification of the putative germinal gene in 3 instances (V kappa IV, Humkv325, and V lambda III.1); the overall ratios of replacement:silent mutations (R:S) were 6.5 and 1.2 in the complementarity-determining regions (CDRs) and framework regions (FRs), respectively. The 2 other lambda sequences belonged to the V lambda III family. With regard to VH domains, 3 of 5 derived from previously identified germline genes (VHIV 4.19, VHIV 4.22, and VHIII 9.1); the overall R:S ratio for these genes was 8 and 1.5 in CDRs and FRs, respectively. CONCLUSION: Taken together, these data provide evidence that the repertoire of human antilamin autoantibodies is not restricted and that the antigen (or another kind of selective pressure) plays a role in the generation of autoantibodies to lamin B. This hypothesis is in accordance with the reactivity of these antibodies to discrete epitopes of lamin B. PMID- 8216426 TI - Concomitant development of chronic active hepatitis and antibodies to ribosomal P proteins in a patient with systemic lupus erythematosus. AB - We describe a systemic lupus erythematosus (SLE) patient who for several years had typical SLE features and positive antinuclear antibodies (ANA), including anti-native DNA. Over the course of a year, 4 years after the SLE was diagnosed, the ANA disappeared and antibodies to cytoplasmic component ribosomal P protein (anti-P) appeared. Associated with the appearance of anti-P antibodies was the development of biochemical evidence of liver disease, later shown histologically to be chronic active hepatitis. The temporal relationship between the occurrence of anti-P antibodies and the development of liver disease raises the possibility of a role for anti-P antibodies in liver disease. PMID- 8216427 TI - Isolation of varicella zoster virus from the synovial fluid of a patient with herpes zoster arthritis. PMID- 8216428 TI - Arthroscopy in rheumatology training programs associated with NIH multipurpose arthritis centers: results from a survey of program directors. PMID- 8216429 TI - Demographic differences in the frequencies of scleroderma-related autoantibodies. PMID- 8216431 TI - The regulatory role of doxycycline/tetracycline in collagenolytic activity and tissue destruction in joint diseases: comment on the article by Yu et al. PMID- 8216430 TI - Hypothalamic response in rheumatoid arthritis: does it justify the use of steroids? PMID- 8216432 TI - Involvement of the serotonergic system in the mode of action of the new potential antidepressant agent 5-methoxyindolyl-2-methylamine. AB - 5-Methoxyindolyl-2-methylamine (PIM-35) is an indole derivative with effects in animals indicative of antidepressant properties. In the present study an attempt was made to gain some insight into the mechanism of its pharmacological activity. PIM-35 was compared with some antidepressants in tests for serotonin (5HT), noradrenaline (NA) and dopamine (DA) uptake inhibition in vitro. PIM-35 is a weak inhibitor of noradrenaline uptake as compared with the standards used. The IC50 value for dopamine uptake was similar to the value for imipramine and higher than that for amitriptyline, both these standards being considered as inhibitors of dopamine uptake. The influence of PIM-35 on serotonin uptake has been studied in a very preliminary experiment after single dose administration to rats. In a similar way paroxetine and chlorimipramine were studied. The inhibition produced by PIM-35 is similar to that produced by the standards. Radioligand binding techniques in rat brain ex vivo showed that chronic administration of PIM-35 produced no variation in the number or the affinity of alpha 2, beta 1- and beta 2-adrenoceptors. PIM-35 inhibits by 40% the number of 5HT2 receptors and does not modify the affinity for the ligand. PIM-35 has activity on the serotonergic system and in this way is similar to the antidepressants paroxetine and chlorimipramine. PMID- 8216433 TI - Effects of the novel thyrotropin-releasing hormone analogue Na -((1S,2R)-2-methyl 4-oxocyclopentylcarbonyl)-L-histidyl-L-prol ina mide monohydrate on the central nervous system in mice and rats. AB - The central nervous system (CNS) effects of a novel thyrotropin-releasing hormone (TRH) analogue, JTP-2942 (Na-alpha- ((1S,2R)-2-methyl-4-oxocyclopentylcarbonyl)-L histidyl-L-pro linamide monohydrate, CAS 131404-34-7) were investigated and compared with those of TRH. When administrated subcutaneously, JTP-2942 was about 80 times more potent than TRH in the antagonization of reserpine-induced hypothermia, and when administrated intravenously it was about 16 times more potent than TRH in the potentiation of flexor reflexes. Furthermore, oral administration of JTP-2942 was able to antagonize a chlorpromazine-induced reduction in locomotor activity, while TRH was far less effective. In tests on the recovery from pentobarbital-induced sleep and disturbance of consciousness induced by concussive head trauma, JTP-2942 was about 30 and 3 times more potent than TRH, respectively. Thus, JTP-2942 had a far stronger and more persistent action compared with TRH in regard to these effects. However, JTP-2942 had a 3 fold lower effect on thyroid stimulating hormone (TSH) release than TRH. These results suggest that the stimulatory effects of JTP-2942 are selective for the CNS and that this TRH analogue may be applicable to clinical use. PMID- 8216434 TI - Preparation and central action of propofol/hydroxypropyl-beta-cyclodextrin complexes in rabbits. AB - Inclusion complexes of propofol (CAS 2078-54-8) and hydroxypropyl-beta cyclodextrin (HP-beta-CD) were examined in aqueous solution and in the solid state by phase solubility technique, IR-spectroscopy and differential scanning calorimetry. Solid complexes obtained by kneading method were dissolved in artificial plasma leading to a colloidal solution which was suitable for intravenous administration. In the in vivo studies propofol (15 mg/kg) was given intravenously to rabbits in equimolar doses as cyclodextrin complexes and as Diprivan. The central action of the drug was verified by recording the bioelectrical activity of the precentral cortex. The statistical evaluation of the results do not indicate differences in onset, duration and maximum of action between the two dosage forms. PMID- 8216435 TI - Effects of cytidine diphosphate choline on rats with memory deficits. AB - The effects of cytidine diphosphate choline (CDP-choline, CAS 987-78-0) on learning and memory in rats with memory deficits were examined using behavioral methods of active avoidance with punishment reinforcement (shuttle-box), passive avoidance with punishment reinforcement (step-through and step-down), and active avoidance with positive (alimentary) reinforcement (staircase-maze). In the majority of experiments CDP-choline was applied orally at doses of 10-50 or 100 mg/kg daily for 7 days before the training session. The experiments were carried out on young-adult (aged 5 months) and old (aged 22 months) rats and on rats with a low capability for retention of learned behavior. Memory deficits were induced by the muscarinic cholinoceptor antagonist scopolamine (in young and old rats and mice), by the alpha 2-adrenoceptor agonist clonidine, by electroconvulsive shock, and by hypoxy. Memory deficits were also induced in rats offspring of dams that had been exposed to alcohol during pregnancy and lactation. The results suggest that CDP-choline acts as a memory-enhancing drug and that its effect is particularly pronounced in animals with memory deficits. PMID- 8216436 TI - Synthesis and biological activities of non-peptide angiotensin receptor antagonists with tetrazole replaced imidazole ring. AB - Angiotensin receptor antagonists related to losartan were synthesized in which the imidazole ring was replaced by tetrazole. 1-[4-(2'-Carboxyphenyl)benzyl]-5 butyl tetrazole and 5-[4-(2'-carboxyphenyl)benzyl]-1-butyl tetrazole had antagonist activities versus angiotensin II in the rat isolated uterus assay of 70% and 10%, respectively, of that of the equivalent imidazole compound 1-[4-(2' carboxyphenyl)benzyl]-2-butyl imidazole. These data suggest that the antagonist activity of compounds in this class is not dependent on the direction of the heterocyclic ring dipole, and that there is a preference for substitution of the acid group-bearing side-chain at the N atom rather than the C atom of tetrazole. PMID- 8216437 TI - Studies on the reduction of aortic calcification by alkali citrates in an ex vivo tissue preparation in the rat. AB - The effect of orally administered alkali citrates on the calcification of arterial vessel was studied in the rat. Freshly dissected aortic segments were placed in Millipore diffusion chambers and grafted intraperitoneally. Within 21 days calcification of the media had developed. Under treatment with 2.1 mmol citrate per animal and day a significant decrease in histologically detectable calcification areas occurred, as assessed by greatest thickness and longitudinal expansion. This effect was more pronounced with potassium citrate and potassium sodium citrate, and less marked with sodium citrate. The calcium and phosphorus content of aortic tissue remained unchanged, but magnesium increased significantly. The spheroid particles deposited in the media were characterized in more detail by electron microscopy and elemental microanalysis, X-ray diffraction, and determination of the molar calcium-phosphorus ratio. The combined data suggest that in the model selected for studying biocalcification not mature hydroxyapatite but some precursor of this substance is deposited, and that in animals receiving alkali citrate treatment deposition of amorphous calcium phosphate is likely. It is concluded that in the ex vivo aortic wall preparation oral alkali citrates a) bring about a reduction in calcification areas in the media layer, b) impair the maturation of hydroxyapatite and its deposition in the arterial tissue; c) promote the accumulation of magnesium. Whether these results are of significance for the calcification of arteries in situ and treatment regimens is unknown. PMID- 8216438 TI - Determination of the interaction of 3S-hydroxy-10,11-dihydroquinidine on the pharmacokinetics and pharmacodynamics of warfarin. AB - The investigational antiarrhythmic drug LNC-834 ((9S)-10,11-dihydro-6'-methoxy cinchonan-3,9-diol hydrogen sulfate pentahydrate, CAS 85405-59-0) is structurally related to quinidine. It was investigated, if concurrent administration of LNC 834 affects the single dose pharmacokinetics and pharmacodynamics of warfarin (CAS 81-81-2). The study was performed as an open, randomized two-way cross-over, controlled investigation in 10 healthy volunteers. In treatment A, 2 tablets of LNC-834 (350 mg of hydrated salt corresponding to 226 mg anhydrous free base each) were ingested twice daily for a period of 9 days in total. On the 4th study day, 2 h after the application of LNC-834 in the morning, the volunteers received a mean dose of 0.36 +/- 0.03 mg/kg warfarin orally. In treatment B only warfarin was administered. Pharmacokinetics of warfarin and anticoagulant effect (prothrombin complex activity) were determined from plasma samples withdrawn up to 144 h after administration; LNC-409 (free base of LNC-834) and the metabolite LNC-253 (2'-oxo-analog) were monitored for check of compliance over the same time period. Concurrent administration of LNC-834 decreased significantly the area under the plasma concentration-time curve of warfarin (117,889 +/- 25,010 (A) vs. 125,294 +/- 22,314 ng/ml.h (B); p = 0.0488). Thus, a significant increase in apparent oral clearance (CL/f) of warfarin in the presence of LNC-834 was determined (3.98 +/- 0.63 vs. 3.71 +/- 0.50 ml/min; p = 0.0488). All other pharmacokinetic parameters determined (apparent volume of distribution (V/f), Cmax, tmax, terminal half-life of elimination) were not altered by concurrent treatment with LNC-834.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216439 TI - Bioavailability and pharmacokinetics of a new isosorbide dinitrate spray preparation in healthy volunteers. AB - In the course of this study the bioavailability and pharmacokinetic profile of a newly developed 2.5 mg (per valve release) oral isosorbide dinitrate (ISDN, CAS 87-33-2) spray preparation (Isoket Spray) were determined and compared with the results for an already marketed reference spray preparation following single application. For this purpose, the test and reference spray were examined in 18 healthy volunteers according to a randomized 2-way cross-over design. Blood samples were collected during 12 h p.a. and plasma concentrations of ISDN and its metabolites isosorbide-2-mononitrate (IS-2-MN) and isosorbide-5-mononitrate (IS-5 MN) were quantified by a GC-method. Both sprays showed mean maximum concentrations of ISDN in plasma of nearly 18 ng/ml about 7 min after drug intake with arithmetic mean values for the areas under the curve AUC0-12 of 7.01 (test spray) and 7.30 h.ng/ml (reference spray). For the metabolic products IS-2-MN and IS-5-MN (values for the reference spray in brackets) the corresponding maximum concentrations were 4.15 (4.21) ng/ml and 16.1 (15.9) ng/ml, respectively, and for the areas under the curve AUC0-12 values of 9.75 (9.92) h.ng/ml for IS-2-MN and 104.3 (99.7) h.ng/ml for IS-5-MN in the mean were calculated. Statistical evaluation of all pharmacokinetic parameters revealed bioequivalence between the two preparations. Typical side-effects known and described under isosorbide dinitrate therapy were also observed in this study. PMID- 8216440 TI - Acute antihypertensive effects of the new generation calcium antagonist 3 pyridine carboxylic acid 5-[(cyclopropylamino)-carbonyl]-1,4-dihydro-2,6-dimethyl 4-(2-nitrophen yl) octyl ester on conscious spontaneously hypertensive rats and renal hypertensive rats. AB - The acute antihypertensive effects of 3-pyridine carboxylic acid 5-[(cyclo propylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitroph eny l) octyl ester (NP-252, CAS 132031-81-3) administered orally to conscious spontaneously hypertensive rats (SHRs) and renal hypertensive rats (RHRs) were evaluated using the impedance plethysmographical technique as a modified tail cuff method, and compared with those of nifedipine (NF). In the fitness test of this indirect method, the average value of blood pressure (BP) measured in 7 conscious SHRs was 201 +/- 6.9 mmHg. This value showed good correlation with that (201 +/- 8.8 mmHg) of systolic BP measured by the direct method in the same animals. In the comparative study of antihypertensive activities of the compounds on both models of hypertension using this method, NP-252 and NF dose-dependently lowered BP having a different peak time and restoration after dosing. Therefore, the antihypertensive activities were compared using a 20% effective dose (ED20) for producing hypotension, and the ED20 values of NP-252 and NF were 2.55 and 2.00 mg/kg in SHRs, and 1.25 and 0.67 mg/kg in RHRs, respectively. Moreover, the duration of actions of the compounds were evaluated by the simulated duration time (SDT) which was calculated from the peak time of BP-fall and the pharmacological half life time for the maximum BP-fall and the SDT values of NP 252 and NF were 1.85-4.70 and 0.90-0.75 h in SHRs, and 3.30-12.80 and 0.57-6.90 h in RHRs, respectively. Also, the BP-falls by the compounds were accompanied by an increase in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216441 TI - Therapeutic safety of perindopril in the treatment of mild hypertension with concomitant nephropathy. AB - Angiotensin-converting enzyme (ACE) inhibitors are well established antihypertensives. Their effect on kidney function, however, seems to depend on the pathophysiological mechanisms underlying the clinical symptoms. In one part of the Perindopril and Therapeutic Safety Study (PUTS) the effect of a 6-week treatment with placebo or 4 mg/d of perindopril (Coversum, CAS 82834-16-0) on kidney function and albuminuria was investigated in 56 hypertensives with concomitant nephropathy. The study was performed as multicenter, randomized, placebo-controlled, double-blind study. The results show that perindopril reduced blood pressure effectively. The responder rate determined as a fall in blood pressure at least about 10 mmHg in the perindopril group was 39% vs. 21% in the placebo group. All investigated parameters of kidney function like serum creatinine, creatinine clearance, urinary excretion of albumin and alpha 1 microglobulin remained unchanged during the study. In a subgroup of patients with isolated albuminuria ACE inhibition reduced significantly the urinary albumin excretion (perindopril: -292 +/- 205 mg/g creat. vs. placebo: +61 +/- 48 mg/g creat: p < 0.05). From this study it can be concluded that in hypertension with concomitant nephropathy, except renovascular hypertension and hypertension in renal transplant recipients, ACE inhibition by perindopril will not impair kidney function. In the early phase of nephropathy with isolated albuminuria and normal serum creatinine perindopril improves albuminuria and seems to be even of benefit for the kidney. PMID- 8216442 TI - Dose relationship of stimulated insulin production following intravenous application of glimepiride in healthy man. AB - This study evaluates stimulated insulin production rate (incremental AUC x MCR (metabolic clearance rate) of C-peptide) and blood glucose (BG) response after i.v. administration of glimepiride (Hoe 490, GLI, CAS 93479-97-1) (0.25, 0.50, 0.75, 1.00, 1.25, 1.50 mg) in healthy man (27 +/- 4 yrs). It was shown that i.v. bolus administration of GLI (0.25, 0.50, 1.25 and 1.50 mg) caused a dose-related rise in insulin production from 18 +/- 17 to 25 +/- 13, 36 +/- 14 and 54 +/- 34 pmol/kg body weight, respectively. This effect did not yet plateau at 1.5 mg GLI and was paralleled by a fall in BG (decremental area below BG baseline) by 40 +/- 36, 69 +/- 20, 161 +/- 47 and 113 +/- 62 mmol.min/l. It is concluded that insulin release is increased by i.v. GLI in a dose related manner, while a parallel decline in BG was induced only up to 1.25 mg GLI. The less marked fall of BG after injection of 1.50 mg GLI may reflect interference by insulin counterregulatory hormones secondary to induced hypoglycaemia. PMID- 8216443 TI - Pharmacokinetics of the gastrokinetic agent mosapride citrate after intravenous and oral administrations in rats. AB - The pharmacokinetics and bioavailability of mosapride citrate ((+/-)-4-amino-5 chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2- morpholinyl]methyl]benzamide citrate dihydrate, AS-4370, CAS 112885-42-4) were investigated in rats of both sexes. Plasma levels of mosapride and its des-4-fluorobenzyl metabolite (M-1) were determined after an intravenous dose of 2 mg/kg or an oral dose of 10 mg/kg. There were marked sex-related differences in the mean plasma concentration-time profiles of mosapride after single intravenous and oral administration. After oral administration, the Cmax of the unchanged mosapride in male rats (44 ng/ml) was approximately 1/18 of that in female rats (788 ng/ml). The Cmax of M-1 (277 ng/ml) was 6 times higher than that of mosapride in males, while the Cmax in females (149 ng/ml) was 1/5 of that of mosapride. Male rats exhibited more rapid elimination (t1/2 of 1.9 h) than females (2.8 h). These sex-dependent pharmacokinetics of mosapride in rats would be explained by two reasons: different activity of hepatic drug-metabolizing enzymes to M-1 and partly different distribution volume of mosapride. Oral bioavailability of mosapride was 7% of the dose in males and 47% in females, suggesting extensive first-pass metabolism in males. Once daily 7-day multiple administration did not affect the pharmacokinetics of mosapride both in male and female rats. PMID- 8216444 TI - Pharmacokinetics of the gastrokinetic agent mosapride citrate after intravenous and oral administrations in dogs and monkeys. AB - The pharmacokinetics and bioavailability of mosapride citrate ((+-)-4-amino-5 chloro-2-ethoxy-N-[[4-(4- fluorobenzyl)-2-morpholinyl]methyl]benzamide citrate dihydrate, AS-4370, CAS 112885-42-4), a new gastrokinetic agent, were investigated in dogs and monkeys. Plasma levels of mosapride and its des-4 fluorobenzyl metabolite (M-1) were determined after a single intravenous dose (2 mg/kg) or a single oral dose (10 mg/kg). After intravenous administration, mean plasma levels of mosapride in male dogs and monkeys showed biphasic decrease with t1/2 alpha of 0.3 and 0.6 h, and t1/2 beta of 2.4 and 2.4 h, respectively. Mean concentrations of mosapride increased rapidly and reached the maximum 0.5-1 h after oral administration to male dogs and monkeys, followed by quick decrease with t1/2 of 1.5 and 0.9 h, respectively. The Cmax was 207 ng/ml in dogs and 862 ng/ml in monkeys. The Cmaxs of M-1 in both species were virtually equivalent to those of the unchanged drug. Plasma concentration-time profiles and pharmacokinetic parameters of mosapride and M-1 in female dogs and monkeys were similar to those in males, indicating no sex-related differences in the pharmacokinetics of mosapride in these animal species. Oral bioavailability was 8% of the dose in dogs and 14% in monkeys, suggesting the extensive first-pass metabolism of mosapride. PMID- 8216445 TI - Pharmacokinetics of the gastrokinetic agent mosapride citrate after single and multiple oral administrations in healthy subjects. AB - The pharmacokinetics and dose proportionality of mosapride citrate ((+-)-4-amino 5-chloro-2-ethoxy-N-[[4- (4-fluorobenzyl)-2-morpholinyl]methyl]benzamide citrate dihydrate, AS-4370, CAS 112885-42-4) were investigated in healthy male volunteers. The subjects were given a single oral dose (5, 10, 20 and 40 mg, each of 5 subjects) and a multiple oral dose (20 mg t.i.d. for one day, and 10 and 20 mg t.i.d. for 8 days, each of 5 subjects). Food effect on the pharmacokinetics of mosapride was also evaluated after a single oral 10 mg dose by an open, two-way crossover method. Mean plasma levels of mosapride reached a peak 0.5-1 h after single dosing of 5, 10, 20 and 40 mg. The peaks were dose-related with values of 25.1, 51.2, 157.8 and 280.6 ng/ml, respectively, and were followed by a first order decrease with apparent half-lives of 1.4-2.0 h. The Cmax and AUC increased in proportion to the dose, indicating linear pharmacokinetics of mosapride up to 40 mg. The Cmax of M-1, a des-4-fluorobenzyl metabolite, was 1/6 of that of the unchanged drug. Urinary excretion of the unchanged mosapride and M-1 during 48 h after single dosing accounted for 0.1-0.4% and 7.0-11.0% of the dose, respectively. There were no significant changes in the plasma concentration-time profiles and urinary excretions between single and multiple doses, indicating that the pharmacokinetics of mosapride in man was not altered by its multiple administration. Plasma levels of mosapride reached steady state on day 2 of multiple administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216446 TI - Pharmacological studies on taurohyodeoxycholic acid. AB - In this study we investigated the anticholelithogenic and choleretic activities and the general pharmacological action of taurohyodeoxycholic acid (THDCA, Io, Praxis, CAS 2958-04-5), a new biliary acid advocated for use as anticholelithogenic agent. THDCA had no significant activity on the CNS (spontaneous locomotor activity, body temperature, coordinated movement, respiration); it also had no significant anticonvulsant or central anticholinergic actions. With regard to the action on the cardiovascular system, THDCA administration did not give rise to significant changes in blood pressure or ECG. Investigation of its action on the gastrointestinal system revealed no significant changes in the intestinal transport of charcoal after treatment. However, biliary flow and biliary solids content were increased by THDCA intraduodenal doses of 300 mg/kg b.w. In mice fed with lithogenic diet THDCA administration (230 and 450 mg/kg b.w. for 8 weeks) significantly decreased gallstone and steatosis incidence. PMID- 8216447 TI - Chronic toxicity of taurohyodeoxycholic acid in rats. AB - Fifty-two-week oral toxicity and 24-week intraperitoneal toxicity of a new synthetized biliary acid, taurohyodeoxycholic acid (Io, Praxis, CAS 2958-04-5), were investigated in rats. Taurohyodeoxycholic acid was orally administered at dose levels up to 500 mg/kg/d and intraperitoneally administered at dose levels up to 200 mg/kg/d. The treated animals showed no deviations from normality in mortality, physical appearance and general behavior. Food and water consumption and body weight gain of the treated groups did not differ from those of the control. No treatment-related changes were observed in hematology, serum biochemistry, urinalysis, organ weights and post-mortem macroscopic or histopathological examinations. No dose- or sex-related differences were observed. The no-effect dose level was estimated to be 500 mg/kg/d in the chronic oral toxicity study and 200 mg/kg/d in the intraperitoneal study. PMID- 8216448 TI - Chronic toxicity of taurohyodeoxycholic acid in dogs. AB - Fifty-two-week oral toxicity and 24-week intramuscular toxicity of a new synthetized biliary acid, taurohyodeoxycholic acid (Io, Praxis, CAS 2958-04-5) were investigated in dogs. Taurohyodeoxycholic acid was orally administered at dose levels up to 500 mg/kg/d and i.m. administered at dose levels up to 200 mg/kg/d. No deviations from normality were observed in mortality, physical appearance and general behaviour of the treated animals. Food and water consumption and body weight gain of treated groups did not differ from those of control animals. No treatment-related changes were observed in hematology, serum biochemistry, urinalysis, organ weights and post-mortem macroscopic or histopathological examinations. No dose- or sex-related differences were observed. The no-effect dose level was estimated to be 500 mg/kg/d in the chronic oral toxicity study and 200 mg/kg/d in the intramuscular study. PMID- 8216449 TI - Reproductive toxicity of taurohyodeoxycholic acid. AB - The reproductive toxicity of taurohyodeoxycholic acid (3 alpha, 6 alpha-dihydroxy 5-beta-cholanoyl-2-amino-ethyl-sulfonic acid, THDCA, Io, Praxis, CAS 2958-04-5), a new synthetized biliary acid patented in Europe, Japan and the United States for prevention and therapy of gallstones and related symptoms, was assayed by performing segment I (fertility and general reproductive performance) and segment II (teratology) studies. In the first study THDCA was administered (100, 220 or 500 mg/kg by oral route) to male and female rats prior to and in the early stage of pregnancy. No adverse effects or dose-related abnormalities were observed in the reproductive performance of either sex; no death or evidence of teratogenicity in fetuses were also observed. In the second study THDCA was administered (100, 220 or 500 mg/kg by oral route) to rats and rabbits during the fetal organogenesis period. No maternal toxicity, teratogenicity or adverse effects on growth of embryos and fetuses and no reduction of the viability index were observed. From these studies the no-effect dose can be estimated at 500 mg/kg. PMID- 8216450 TI - In vitro and in vivo mutagenicity studies on taurohyodeoxycholic acid. AB - The mutagenicity of a new biliary acid, taurohyodeoxycholic acid (THDCA, Io, Praxis, CAS 2958-04-5), was assayed by using 5 different tests. The Ames test (reverse mutation assay on Salmonella typhimurium) and the DNA damage and repair test (in Saccharomyces cerevisiae) allowed to study the genetic THDCA-induced mutations in prokaryotes and eukaryotes (doses of 100, 200 and 400 micrograms/plate or 100, 200 and 400 micrograms/ml, respectively). In vivo and in vitro chromosomal aberrations were studied by using micronucleus test in mice (doses of 100, 220 and 500 mg/kg in oral study and 50, 100 and 200 mg/kg in subcutaneous study) and human lymphocytes cytogenetic test (doses of 50, 100, 220 and 500 micrograms/ml of THDCA). At last the host-mediated assay was performed on THDCA-treated mice (following oral or subcutaneous administration) in order to test the potential mutagenic activity of its metabolites on a S. typhimurium strain. The results obtained in these studies showed that THDCA did not induce any signs of promutagenic, mutagenic or clastogenic direct or metabolite-mediated activity. PMID- 8216451 TI - Effects of ketotifen on human lymphocytes in vitro and in vivo. AB - The effects of the antiasthmatic drug ketotifen (CAS 34580-13-7) on human mononuclear leukocytes were studied in vitro and in vivo. In vitro ketotifen concentration-dependently inhibited mitogen-stimulated lymphocyte proliferation. High ketotifen concentrations also inhibited T-lymphocyte mitogen- and adenosine triphosphate stimulated increases in intracellular Ca2+ in lymphocytes and the U937 human monocyte precursor cell line, respectively; this involved inhibition of both Ca2+ influx and intracellular mobilization. In in vivo experiments, treatment of healthy volunteers with 1 mg ketotifen b.i.d. for 7 d did not alter the number or subset composition of circulating lymphocytes. Moreover, the mitogen-stimulated in vitro proliferation of lymphocytes obtained before and after ketotifen treatment in vivo was similar. It is concluded that high ketotifen concentrations can inhibit the activation of resting lymphocytes in vitro but standard ketotifen treatment does not notably affect the number of function of circulating lymphocytes in vivo. PMID- 8216452 TI - Synthesis and biological activity of a series of aryl tropanyl esters and amides chemically related to 1H-indole-3-carboxylic acid endo 8-methyl-8 azabicyclo[3.2.1]oct-3-yl ester. Development of a 5-HT4 agonist endowed with potent antinociceptive activity. AB - A series of aryl tropanyl esters and amides related to 1H-indole-3-carboxylic acid endo 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester (ICS 205930, CAS 89565-68-4) were synthesized and evaluated for antinociceptive activity using the hot-plate test. Of these, the benzofurane-3-carboxylic ester of tropine (1) was found powerfully to increase the pain threshold, with a cholinergic mechanism of action. Despite the structural similarity with ICS 205930, the analgesia induced by 1 seems not to be due to 5-HT3 receptor interaction, and there is evidence of involvement of the central 5-HT4 receptor. PMID- 8216453 TI - Percutaneous absorption of ibuprofen from different formulations. Comparative study with gel, hydrophilic ointment and emulsion cream. AB - In a three-way cross-over study on 6 healthy adult volunteers, the percutaneous absorption of ibuprofen (CAS 15687-27-1) was studied with 3 topical formulations containing 5% w/w ibuprofen in a gel (Iprogel) or in a hydrophilic ointment or in an emulsion cream. By analysis of the plasma drug concentrations appearing after topical application, the relative drug bioavailability was calculated in terms of Cmax (maximum blood concentration of the drug), AUC (area under the curve of drug plasma concentrations at various time points) and Tmax (the time required for appearance of maximum drug concentration in the blood). The gel formulation showed the highest drug concentration in blood, reached in the shortest period, whereas that from the hydrophilic ointment showed the lowest drug concentration, reached at the slowest rate. The absorption from the reference product containing the drug as an o/w emulsion cream was less than with the gel formulation but higher than that found with the hydrophilic ointment. PMID- 8216455 TI - Concentrations of cefodizime in bronchial secretions after single intravenous administration. AB - The concentrations of cefodizime (HR 221, CAS 69739-16-8) in bronchial secretions were measured after administration of a single intravenous bolus of 2 g in 19 patients requiring fibreoptic bronchoscopy for diagnostic purposes or as therapeutic follow-up. These concentrations, which were obtained in absence of inflammation of the mucosa, were compared to serum concentrations obtained simultaneously. The penetration into bronchial secretions was rapid, maximum levels of between 1 and 5 mg/kg being already observed 1 h after injection. Most concentrations remained about 1 mg/kg throughout the whole observation period of about 5.5 h. The percent penetration amounted to about 1.5% of the corresponding serum concentrations. CONCLUSION: Concentrations well above the MIC90s of the relevant respiratory pathogens--S. pneumoniae, M. catarrhalis, H. influenzae, K. pneumoniae--and Enterobacteriaceae were reached in bronchial secretions after intravenous injection of a single 2 g dose of cefodizime. Even higher levels may be expected in the usual condition of inflamed bronchial mucosa as found in respiratory infections. PMID- 8216454 TI - Bactericidal effect of propolis in vitro against agents causing upper respiratory tract infections. AB - Propolis is a natural product of bees which exhibits an antimicrobial effect. In the study the existence of a bactericidal effect against several strains isolated from patients with infections in their upper respiratory tracts is demonstrated. In light of the use of propolis as a therapeutic agent in natural medicine for common colds and inflammatory processes this effect is discussed. PMID- 8216456 TI - Pharmacokinetics in rats, dogs and monkeys of a gadolinium chelate used as a liver-specific contrast agent for magnetic resonance imaging. AB - The introduction of the lipophilic moiety, ethoxybenzyl, into the gadolinium chelate dimeglumine gadopentetate (Gd-DTPA, Magnevist, CAS 86050-77-3) yielded (4S) 4-(4-ethoxybenzyl)-3,6,9-tris (carboxylatomethyl)-3,6,9-triazaundecandioic acid, gadolinium complex, disodium salt (Gd-EOB-DTPA), a compound with a potential as a magnetic resonance contrast agent for liver mass screening. Both in the rat and in the dog the pharmacokinetics of Gd-EOB-DTPA were nonlinear in the dose range of 0.05-0.5 mmol/kg (rat) and 0.03-0.25 mmol/kg (dog) since after correction for the difference in dose the plasma concentration-time profiles were not superimposable and the amounts excreted renally and fecally differed significantly (p < 0.05). Extrarenal elimination played an important role since fecal elimination (% of dose) was 73.4 +/- 5.6 in rats (0.05 mmol/kg), 70.1 +/- 4.0 in dogs (0.03 mmol/kg) and 32.1 +/- 6.4 in monkeys (0.25 mmol/kg). However, in all species investigated, the values of renal clearance (Clr) were independent of dose and close to the value of the glomerular filtration rate (Clr in ml/min.kg: 10.4 +/- 3.5 in rats; 3.88 +/- 0.8 in dogs; 1.01 +/- 0.3 in monkeys). Therefore, the pharmacokinetics of Gd-EOB-DTPA can best be described by a capacity-limited transport process via the biliary route of elimination thus strongly resembling the pharmacokinetics of some biliary X-ray contrast media (iotroxic, iodipamic or idoxamic acid) or the synthetic dyes (indocyanine green). However, contrary to the latter agents the plasma binding (%) of Gd-EOB-DTPA was low in all species (10.3 +/- 1.4 in rats: 10.0 +/- 1.3 in dogs; 17.5 +/- 1.0 in monkeys). PMID- 8216457 TI - [Adverse effects of a new non-ionic contrast medium in heart catheterization]. AB - Tolerance of a New Non-ionic Contrast Medium during Heart Catheterization The new non-ionic contrast medium iomeprol (CAS 78649-41-9) was investigated for adverse reactions and diagnostic quality in 75 patients undergoing heart catheterization. Blood pressure and ECG were continuously registered. The patients were asked for subjective complaints by using a standardized questionnaire. Experienced cardiologists assessed the diagnostic quality of the angiograms. With iomeprol neither fatal nor severe reactions were observed. The dye had only little influence on diastolic and systolic blood pressure; heart rate was not significantly influenced. Minor and partly moderate adverse reactions all being completely reversible were observed in 14 patients (18.7%). One patient complained of strong heat sensation after dye injection into the left ventricle. The diagnostic quality of the angiograms allowed to make a definitive diagnosis in all cases. Thus, iomeprol proved to be a suitable and safe contrast medium for heart catheterization. PMID- 8216459 TI - Teams and teamwork. Educational settings. PMID- 8216458 TI - Teams and teamwork. Health care settings. PMID- 8216460 TI - Teams and teamwork. Academic settings. PMID- 8216462 TI - Children deserve choice. PMID- 8216461 TI - Teams and teamwork. An audiology perspective. PMID- 8216463 TI - Cleft lip and palate and craniofacial treatment. PMID- 8216464 TI - Teams and teamwork. A rural/remote perspective: Alaska. PMID- 8216465 TI - Teams and teamwork. Strategies for improvement. PMID- 8216466 TI - Teams and teamwork. Reflections on leadership. PMID- 8216467 TI - Infection control procedures in universities. PMID- 8216468 TI - Universal hearing screening of newborns. An idea whose time has come. PMID- 8216469 TI - Consumers advised to consult audiologists after FDA warning issued to hearing aid manufacturers. PMID- 8216470 TI - Success in the schools. PMID- 8216471 TI - Audiology and the medical community: developing an marketing plan [corrected]. PMID- 8216472 TI - Targeting the hearing aid population. PMID- 8216473 TI - Successful recruiting strategies. AB - Key aspects of a successful recruitment program to attract bright, talented students to this dynamic profession are (a) providing informative and attractive printed materials about the professions and the program, (b) establishing key personnel to provide personal contact with each student applicant, (c) specifying deadlines for application submission and decisions, (d) providing efficient feedback, (e) maintaining consistent contact with students prior to matriculation, and (f) offering several social and academic activities to orient new students. Although concepts important to retention are not included here, they are similarly important and should be considered carefully. Given the cyclical nature of student enrollment in the professions, a program's emphasis on recruitment may change. However, in order to keep student enrollment levels constant, consistent recruitment is necessary. PMID- 8216474 TI - Reaching multicultural populations. PMID- 8216475 TI - Improving third party coverage. PMID- 8216476 TI - Making media work for you. PMID- 8216477 TI - Developing the message: let the challenge begin! PMID- 8216478 TI - In praise of public school clinicians. PMID- 8216479 TI - In praise of public school clinicians. PMID- 8216480 TI - Response to Duffy. PMID- 8216481 TI - To walk a mile in my moccasins. PMID- 8216482 TI - Tips for creating competitive advantage. PMID- 8216483 TI - Computer technology. History and overview. PMID- 8216484 TI - Computer technology. Emerging technology meets universal grammar. PMID- 8216485 TI - Computer technology. Use in training programs. PMID- 8216486 TI - Computer technology. Use in language analysis. PMID- 8216487 TI - Computer technology. Hypercard: the high-tech flannel board. PMID- 8216488 TI - Computer technology. Clinical applications of biofeedback. PMID- 8216489 TI - Computer technology. Technology-enhanced accent modification. AB - A number of technological advances have made it feasible to use personal computers to enable nonnative speakers of American English to see, as well as hear, differences between their own speech and model utterances. This article has important implications for incorporating the use of technology in accent modification practices. PMID- 8216490 TI - Computer technology. Use in public schools. AB - By using the computer in the ways mentioned, students learn important communication skills. The fact that they have fun in the process is an added bonus and a great motivator for changing behavior. The information given is by no means all-inclusive. Each speech-language pathologist can use his or her own ideas and creativity to develop treatment materials. The possibilities are endless. PMID- 8216491 TI - Computer technology. Computing competencies for clinicians. PMID- 8216492 TI - Humans better subjects for research. PMID- 8216493 TI - Computer technology. Integration into office management. PMID- 8216494 TI - Task Force on Health Care. AB - The five leading issues identified, in order of importance, were 1. The need for treatment outcome and efficacy data. 2. The need for changes in clinical and academic preparation of entry-level practitioners. 3. The lack of inclusion or use of services for communication and related disorders in public and private health care programs. 4. The need for greater professional autonomy within the health care system. 5. The need to improve services to underserved populations with communication and related disorders. This report was forwarded to key National Office staff and appropriate ASHA boards, councils, and committees for the purposes of determining its feasibility and developing a national plan for action. The feasibility and action plan will detail completed, ongoing and future activities of the Association related to each issue, recommendation, and strategy. Periodic review of the actions taken and progress achieved will be monitored by the Executive Board, other appropriate boards and councils, and designated National Office staff. The plan represents a progressive view of needed change for the professions of speech-language pathology and audiology within the context of the broader health care delivery system. PMID- 8216495 TI - More biology, genetics for undergrads. PMID- 8216496 TI - The FDA says: "see an audiologist". PMID- 8216497 TI - Effects of physiological plasma insulin levels on glucose turnover parameters in familial hypercholesterolemia. AB - Eight young, non-obese patients with primary familial hypercholesterolemia (FH) and 8 healthy subjects matched for age, body mass index, lean body mass, plasma triglyceride and HDL-levels and arterial blood pressure were selected from a lipid clinic. Patients with FH had higher plasma LDL-cholesterol (8.3 +/- 0.5 vs. 4.1 +/- 0.2 mmol/l, P < 0.001) than controls but similar plasma triglyceride (1.15 +/- 0.04 vs. 1.10 +/- 0.02 mmol/l P = NS) levels. Both study groups were submitted to a euglycaemic hyperinsulinemic glucose clamp combined with simultaneous infusion of [3H]glucose to measure insulin action on whole-body glucose uptake and on hepatic glucose production. Two insulin infusion rates (0.15 mU/kg per min from 0 to 120 min and 0.30 mU/kg per min from 121 to 240 min) were used resulting in similar plasma insulin levels in both groups studied. Our results demonstrate that both whole-body glucose uptake and hepatic glucose output are similar in the fasting state as well as during insulin administration in both groups of subjects. We conclude that, in the absence of other causes of insulin resistance, isolated hypercholesterolemia is associated with normal sensitivity to insulin in both liver and peripheral tissues. PMID- 8216498 TI - Relationship between mevalonate pathway and arterial myocyte proliferation: in vitro studies with inhibitors of HMG-CoA reductase. AB - The role of mevalonate and its products (isoprenoids) in the control of cellular proliferation was examined by investigating the effect of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (vastatins) on growth and on cholesterol biosynthesis of cultured arterial myocytes (SMC). Simvastatin (S) and fluvastatin (F), but not pravastatin (P), decreased the rate of growth of rat vascular SMC. The inhibition, evaluated as cell number, was dose-dependent with IC50 values of 2.8 and 2.2 microM for S and F, respectively; P (1-500 microM) was inactive. The inhibition of cell growth induced by 3.5 microM S (70% decrease) was prevented completely by the addition of 100 microM mevalonate, partially (70-85%) by the addition of 10 microM geraniol, 10 microM farnesol and 5 microM geranylgeraniol, but not by the addition of squalene, confirming the specific role of isoprenoid metabolites in regulating cell proliferation. All the tested vastatins inhibited the incorporation of [14C]acetate into cholesterol but P had 800 times lower potency than S and F. Similar results were obtained in SMC from human femoral artery. At least 80% inhibition of cholesterol synthesis was necessary to induce a decrease in SMC proliferation. To further investigate the relationship between cholesterol synthesis and cell growth, two enantiomers of F were investigated. The enantiomer more active on HMG-CoA reductase was 70- and 1.6-fold more potent on arterial myocyte proliferation than its antipode and the racemic mixture, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216499 TI - Evidence for the presence of early vascular lesions in newborn Watanabe heritable hyperlipidemic (WHHL) rabbits. AB - We have investigated the morphology of the aortic wall of newborn New Zealand White (NZW) (n = 10) and newborn Watanabe heritable hyperlipidemic (WHHL) (n = 10) rabbits. In both strains, lipid levels (cholesterol and triglycerides) were elevated above the concentrations expected. This was particularly evident in WHHL. The morphology of the aortas of NZW rabbits suggested an intensive biosynthetic and bioenergetic activity of endothelium. This was most evident in areas where blood flow underwent division. No major abnormalities were noted in the endothelium or subendothelium. In newborn WHHL rabbits, leucocyte adhesion (usually monocytes) to endothelium and migration into the subendothelium was apparent, particularly on the aortic arch and around areas of dividing blood flow in the thoracic aorta. Tuberous raised structures were present in low numbers and distributed randomly on the aortic wall. Endothelial cells had elevated nuclear zones projecting into the vessel lumen. At regions of blood flow division, endothelium was polygonal in shape and silver staining of cell borders was more intense. Fatty streaks were present at blood flow divisions and micro-plaque was seen. Transmission electron microscopy of fatty streak-like areas showed the presence of up to two layers of smooth muscle cells and in some areas, lipid laden macrophages were seen. The presence of atherosclerotic lesions in newborn WHHL rabbits suggests that the process may commence in utero. PMID- 8216500 TI - Different expression of modified low density lipoprotein receptors in rabbit peritoneal macrophages and Kupffer cells. AB - We have previously reported that mouse peritoneal macrophages have three types of modified low density lipoprotein (LDL) receptors. One is specific for acetylated LDL (Ac-LDL), the second is for oxidized LDL (Ox-LDL), and the third recognizes both (Arai, H. et al. (1989) Biochem. Biophys. Res. Commun. 159, 1375-1382). In the current study, the characteristics of modified LDL receptors in rabbit peritoneal macrophages and Kupffer cells from rabbits were investigated. Cross competition studies of the degradation assay between Ox-LDL and Ac-LDL in rabbit peritoneal macrophages showed that the degradation of 125I-labeled Ox-LDL was almost completely inhibited by an excess amount of unlabeled Ac-LDL. On the other hand, an excess amount of unlabeled Ox-LDL suppressed 125I-labeled Ac-LDL degradation only partially. In contrast, in Kupffer cells an excess amount of unlabeled Ox-LDL inhibited the degradation of 125I-labeled Ac-LDL almost completely, whereas the degradation of 125I-labeled Ox-LDL was inhibited only partially by Ac-LDL. Scatchard analysis of binding assay showed that rabbit peritoneal macrophages have a single class of receptor for Ox-LDL, which binds maximally 0.31 microgram/mg cellular protein (Bmax) with an apparent dissociation constant (Kd) of 19.3 micrograms/ml, and two classes of receptors for Ac-LDL; one with high affinity (Bmax 0.025 microgram/mg cellular protein, Kd 0.040 micrograms/ml) and the other with low affinity (Bmax 0.08 microgram/mg cellular protein, Kd 11.31 micrograms/ml). On the other hand, Kupffer cells have two classes for Ox-LDL; one is a high affinity receptor (Bmax 0.53 microgram/mg cellular protein, Kd 0.99 microgram/ml) and the other is a low affinity receptor (Bmax 3.71 micrograms/mg cellular protein, Kd 16.2 micrograms/ml) and a single class for Ac-LDL (Bmax 0.60 microgram/mg cellular protein, Kd 7.24 micrograms/ml). These results indicate that rabbit peritoneal macrophages have two kinds of modified LDL receptors; one is specific for Ac-LDL, and the other recognizes both Ox-LDL and Ac-LDL. PMID- 8216501 TI - Marathon runners presented lower serum cholesteryl ester transfer activity than sedentary subjects. AB - Acute exercise promotes raised HDL cholesterol concentrations by lipolysis stimulation, but this effect is insufficient to explain the more permanent HDL increases seen during regular exercise. During training periods in a group of marathon runners, we measured lipid transfer protein I (LTP-I)-mediated cholesteryl ester transfer activity (CETA) and its relationship to their HDL concentrations. Runners of both sexes showed significantly lower CETA values than those of sedentary controls. Male runners also had significantly lower serum concentrations of triglyceride, VLDL cholesterol and apolipoprotein B, and significantly higher concentrations of HDL cholesterol and apolipoprotein A-I than male controls. Results indicate that regular practice of aerobic exercise promotes modifications of lipoprotein metabolism related not only to lipolysis, but also to lower CETA. Such modifications are associated with reduced risk of atherosclerosis. PMID- 8216502 TI - SK&F 97426-A a more potent bile acid sequestrant and hypocholesterolaemic agent than cholestyramine in the hamster. AB - SK&F 97426-A is a novel bile acid sequestrant which was selected for comparison with cholestyramine in vivo because of its superior in vitro bile acid binding properties. The effects of the two sequestrants on faecal bile acid excretion, plasma total cholesterol, VLDL + LDL and HDL cholesterol and triglyceride concentrations and on liver enzymes involved in the synthesis and metabolism of cholesterol were investigated in normocholesterolaemic hamsters. Four studies were conducted to determine the relative potencies of the two resins using a range of doses of the sequestrants over treatment periods of up to 2 weeks. Curves fitted to the resulting data allowed common maximum responses and separate ED50s to be calculated for each sequestrant. The maximum response of both sequestrants was to increase bile acid excretion by 352% and lower plasma total cholesterol by 37-58%. LDL + VLDL and HDL cholesterol were reduced by 56-75% and 25-41%, respectively. SK&F 97426-A was 3 times more potent than cholestyramine at increasing the excretion of bile acids in the faeces and 2.1-3.4-fold and 2.3-3.2 fold more potent at lowering total plasma cholesterol and LDL plus VLDL cholesterol, respectively. In some of the experiments SK&F 97426-A was also more potent than cholestyramine at lowering HDL cholesterol. Plasma triglycerides were also lowered by both sequestrants by up to 31% after 1 week but the relative potency could not be determined. These HDL cholesterol and total triglyceride lowering effects of bile acid sequestrants in the hamster are known not to occur in people treated with cholestyramine. There were minimal differences between hamsters treated for 1 or 2 weeks in the relative potencies or ED50s calculated for the total plasma cholesterol, LDL + VLDL and HDL cholesterol. Both sequestrants may have been slightly more efficacious on these parameters after 2 weeks of treatment. Liver weights were reduced by about 15% by both sequestrants at 2% (w/w) in the diet for 1 week. The activities of the liver HMG-CoA reductase and cholesterol 7 alpha-hydroxylase were increased as expected, whilst the activity of the acyl-CoA:cholesterol acyltransferase was reduced by both sequestrants at this dose. SK&F 97426-A was, therefore, 2-3-fold more potent as a bile acid sequestrant and hypocholesterolaemic agent than cholestyramine when tested in the hamster. PMID- 8216504 TI - Relation of lipoprotein(a) to coronary heart disease and duplexsonographic findings of the carotid arteries in heterozygous familial hypercholesterolemia. AB - In familial hypercholesterolemia (FH) elevated Lp(a) concentrations are more frequent than in the general Caucasian population, but the clinical relevance of Lp(a) as a risk-factor in this group of patients is controversial. In 91 adult patients with heterozygous FH due to LDL-receptor defect we analyzed the correlation between Lp(a) concentrations, presence of coronary heart disease (CHD) and degree of atherosclerosis of the carotid arteries assessed by duplex scan. Coronary heart disease was present in 32 patients (24 males, 8 females). In the group without CHD the median of the Lp(a) distribution was 23 mg/dl, in the group with CHD 43 mg/dl (P < 0.05). The median of Lp(a) was 8 mg/dl in patients without pathological changes in the duplex scan of the carotids, 13 mg/dl in the group with intimal thickening, 25 mg/dl in patients with non-obstructing plaques, and 45 mg/dl in presence of > 30% luminal obstruction (P < 0.01). The role of Lp(a) as an independent risk factor was analyzed by stepwise logistic regression together with age, sex, LDL-, HDL-cholesterol, serum triglycerides, smoking status and presence of hypertension. For the prediction of CHD only age, HDL cholesterol and gender reached statistical significance. Lp(a) was, however, the lipoprotein parameter with the highest discriminative strength for the presence of a pathological duplex scan (P = 0.016), followed by LDL- (P = 0.03), and HDL cholesterol (P = 0.03). These results provide direct evidence for a close correlation between Lp(a) and the rate of progression of atherosclerosis in FH, already at early, asymtomatic stages. PMID- 8216503 TI - The effect of nicotinic acid and acipimox on lipoprotein(a) concentration and turnover. AB - This study examines the effect of nicotinic acid (1 g t.d.s.) on serum Lp(a) concentration in a group of patients with type II hyperlipidaemia selected on the basis of a plasma Lp(a) concentration greater than 30 mg/dl. Reductions in total cholesterol, triglyceride, LDL-cholesterol and Lp(a) were 16.3%, 25.5%, 23.7% and 36.4%, respectively, with an increase in HDL cholesterol of 37.3%. The reduction in Lp(a) concentration did not correlate with any other lipoprotein changes. In order to establish the mechanism of the fall in Lp(a) concentration, in vivo turnover of autologous Lp(a) was studied in three subjects before and whilst taking nicotinic acid. The fractional catabolic rate in Lp(a) was unaltered in the subjects on therapy, indicating that nicotinic acid did not increase catabolism of Lp(a) but decreased the synthetic rate. Since nicotinic acid was poorly tolerated we examined the effect of acipimox, an analogue of nicotinic acid on lipoproteins using a placebo controlled double-blind crossover design in a group of hyperlipidaemic patients again selected with plasma Lp(a) concentration greater than 30 mg/dl. Acipimox was better tolerated than nicotinic acid but the percentage changes in lipoprotein concentrations were smaller. PMID- 8216505 TI - Recruitment and dynamics of leukocytes in the formation of arterial intimal thickening--a comparative study with normo- and hypercholesterolemic rabbits. AB - Leukocyte involvement in intimal thickening was investigated as a function of time and diet. Fibromuscular or foam cell-rich thickings were induced by electrical stimulation (ES) of carotid arteries in rabbits either on a normal or a high (1%) cholesterol diet. Under both dietary conditions granulocytes (predominantly neutrophils), monocytes and lymphocytes migrated through and accumulated beneath a continuous, yet structurally altered endothelium already after 1 day of ES. This preceded the occurrence of smooth muscle cells (SMCs) in the intima. Under normocholesterolemia, leukocyte attachment to the endothelium decreased with continued ES, which coincided with the re-establishment of a normal endothelial cell pattern. Neutrophils ceased to invade the stimulated intima and disappeared from the lesion after 14 days. The proportion of mononuclear leukocytes was also reduced in the thickened intima, finally amounting to 5.5 +/- 5.9% in the 4-week-old fibromuscular lesion where SMCs prevailed. Hypercholesterolemia did not affect neutrophil involvement in response to ES. However, it provoked lipid deposition first in macrophages, then in SMCs and resulted in elevated amounts of mononuclear leukocytes both within the foam cell-rich thickening and in association with the overlying endothelium. These data indicate adaptive behavior of leukocytic infiltration in the development of fibromuscular thickening, and a shift to a chronic inflammatory response under additional hypercholesterolemia. PMID- 8216506 TI - Apolipoprotein E phenotype is related to macro- and microangiopathy in patients with non-insulin-dependent diabetes mellitus. AB - The role of apoliprotein E (apo E) in modulating the susceptibility of individuals with non-insulin-dependent diabetes mellitus (NIDDM) to atherosclerotic vascular disease was studied in 143 male and 128 female patients with NIDDM. The data show that the apolipoprotein phenotype E2 somehow protects from macrovascular complications in NIDDM both in men and women. E2 also tends to protect from microvascular complications. In contrast, apo E phenotypes E4/4 and E4/3 tend to increase the risk for macroangiopathy in NIDDM patients. The lower prevalence of macroangiopathy in the subjects with E2 was associated with lower plasma total and LDL cholesterol concentrations and low plasma lipoprotein(a) levels. Overall, this study demonstrates the role of the apo E phenotype to modulate the risk for diabetic complications in patients with NIDDM. The confirmation of the association of apo E polymorphism with diabetic complications warrants, however, long-term follow-up studies. PMID- 8216507 TI - Pravastatin experience in elderly and non-elderly patients. AB - Epidemiologic evidence linking elevated cholesterol concentrations and coronary heart disease (CHD) through the eighth decade of life provides a rationale for lowering cholesterol concentrations to reduce morbidity and mortality from CHD. Pravastatin, a well tolerated HMG CoA reductase inhibitor with a convenient once daily dosing regimen, has been shown to effectively lower total and low density lipoprotein (LDL) cholesterol. Individual data from more than 1800 hypercholesterolemic patients enrolled in six double-blind, randomized, multicenter studies were pooled and then analyzed to compare the safety and efficacy of pravastatin in the elderly (i.e., patients at least 65 years old) and the non-elderly. In short-term studies (8-16 weeks), response was dose-related and similar in elderly and non-elderly subjects. Pravastatin 20 or 40 mg daily lowered total cholesterol 19-25%, LDL-cholesterol 25-33%, and triglycerides 14 23%; high density lipoprotein (HDL) cholesterol increased 5-10%. During long-term studies, improvements were sustained for more than 24 months in both the non elderly and elderly. The incidences of adverse drug events and laboratory abnormalities were similar in the elderly and non-elderly patients in all groups (active treatment control with resin, pravastatin alone, or combination therapy). In short-term studies, treatment was discontinued because of adverse events in < 1% of all patients treated with pravastatin (all doses) or placebo. The frequency and profile of adverse events were similar among patients treated with pravastatin or placebo. In long-term studies, treatment was discontinued in 0.4% of patients in the pravastatin group and in 0.3% of the patients in the bile-acid binding resin group. If drug therapy is warranted, pravastatin appears to be safe and effective for long-term use in elderly patients with hypercholesterolemia. PMID- 8216508 TI - Transport and metabolism of glucose and arabinose in Bifidobacterium breve. AB - Glucose was required for the transport of arabinose into Bifidobacterium breve. The non-metabolisable glucose analogue 2-deoxy-D-glucose (2-DG) did not facilitate assimilation of arabinose. Studies using D-[U-14C]-labelled arabinose showed that it was fermented to pyruvate, formate, lactate and acetate, whereas the principal metabolic products of D-[U-14C]-labelled glucose were acetate and formate. In contrast to glucose, arabinose was not incorporated into cellular macromolecules. A variety of metabolic inhibitors and inhibitors of sugar transport (proton ionophores, metal ionophores, compounds associated with electron transport) were used to investigate the mechanisms of sugar uptake. Only NaF, an inhibitor of substrate level phosphorylation, and 2-DG inhibited glucose assimilation. 2-DC had no effect on arabinose uptake, but NaF was stimulatory. High levels of phosphorylation of glucose and 2-DC by PEP and to a lesser degree, ATP were seen in phosphoenolpyruvate: phosphotransferase (PEP:PTS) assays. These data together with strong inhibition of glucose uptake by NaF suggest a role for phosphorylation in the transport process. Arabinose uptake in B. breve was not directly dependent on phosphorylation or any other energy-linked form of transport but may be assimilated by glucose-dependent facilitated diffusion. PMID- 8216509 TI - A prospective study to identify high-yield criteria associated with acute intracranial computed tomography findings in head-injured patients. AB - We conducted a multicenter, prospective study of head-injured patients to identify high-yield clinical criteria for acute intracranial injuries. Emergency patients with a history of blunt head trauma occurring within 2 weeks and who underwent nonenhanced cranial computed tomography (CT) were entered onto the study during a 12-month period. Of the 264 patients, 32 (12%) had abnormal CT findings. Nine high-yield variables were associated with abnormal CT findings: alcohol use before injury, antegrade amnesia, prolonged loss of consciousness, anisocoria and/or fixed and dilated pupils, abnormal Babinski reflex, focal motor paralysis, cranial nerve deficit, Glasgow coma scale score of less than 15, and clinical signs of basilar skull fracture. Patients 2 years old or younger or older than 60 years of age showed a significantly greater prevalence of abnormal CT findings than patients of other ages. PMID- 8216510 TI - A prospective evaluation of radiologic criteria for head injury patients in a community emergency department. AB - Several management strategies for radiographic evaluation of head-injury patients have been developed, most are based on retrospective analysis. The study attempted to prospectively evaluate the previously published Masters' criteria defining low-, medium-, and high-yield patients. A community hospital emergency department with a low prevalence of serious head injury was studied, and 1,000 consecutive patients 2 years of age presenting with historical or physical evidence of blunt head trauma were asked to participate; 967 consented. The patients were categorized by staff emergency physicians as low-, moderate-, and high-yield for intracranial injury on the basis of their initial history and physical examination. These categories guided imaging decisions in accordance with the guidelines of Masters. The patients were evaluated 6 weeks later by multiple questionnaire and/or telephone calls to determine whether or not undiagnosed head injuries had been missed. The 967 patients initially evaluated were classified according to their risk of intracranial injury as follows: 886 at low risk, 78 at moderate risk and 3 at high risk. Complete follow-up data were available for 895 of these patients (93%). Of the 895, 71 patients (7.9%) did report receiving follow-up medical care for their head injury; none had evidence of missed intracranial injury requiring intervention. Therefore, it can be inferred with a 95% confidence interval that 0.4% or less of patients who were diagnosed as not having intracranial injuries requiring intervention may actually have such injuries. The application of Masters' management strategy in low-risk populations permits clinicians to safely reduce the number of radiographs ordered for patients with head injury. PMID- 8216511 TI - A comparison of the response of near-fatal acute hemorrhage models with and without a vascular injury to rapid volume expansion. AB - Recent studies in which animals were bled from a vascular injury rather than an intravascular catheter demonstrate increased blood loss and mortality with rapid volume expansion. The purpose of this study was to better define the importance of incorporating a vascular injury in animal models of acute hemorrhage. We directly compared the response to resuscitation from hemorrhage of comparable severity in animals with and without a vascular injury. Thirty-four immature swine (14.6 to 23.2 kg) were instrumented and subjected to severe blood loss (40 to 46 mL/kg). Groups I and II were hemorrhaged from a femoral artery catheter only. Groups III and IV were initially bled in the same manner; however, when the mean arterial pressure (MAP) decreased to 30 mm Hg, a 4-mm tear was created in the infrarenal aorta, allowing free intraperitoneal hemorrhage. In all groups, the catheter hemorrhage was discontinued once the pulse pressure reached 5 mm Hg. Groups II and IV were resuscitated with normal saline (NS) infused at a rate of 6 mL/kg/min followed by shed blood at a rate of 2 mL/kg/min. The resuscitation fluids were infused as needed to maintain a MAP of 80 mm Hg. Groups I and III served as controls and were not resuscitated. All animals were observed for 60 minutes or until death. The data were compared using repeated measures analysis of variance with a post hoc Tukey Kramer and the Fisher's exact test. Mortality was 100%, 0%, 88%, and 78% for groups I, II, III, and IV, respectively (P < .05 for group II vs groups I, III, and IV).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216512 TI - Effect of hypertonic sodium bicarbonate in the treatment of moderate-to-severe cyclic antidepressant overdose. AB - The objective of this study was to characterize the effect of intravenous hypertonic sodium bicarbonate (NaHCO3) administration in patients with moderate to-severe cyclic antidepressant (CA) overdose. We reviewed charts of all 91 patients given the diagnosis of CA overdose in the University of California Los Angeles (UCLA) Emergency Medicine Center (EMC), who either died in the EMC or were admitted to the medical intensive care unit (MICU), and who received NaHCO3 in the EMC between 1980 and 1988. Twenty-four other patients with the same EMC diagnosis were admitted to the MICU during this period but did not receive NaHCO3. The response of blood pressure, electrocardiographic parameters, and mental status to serum alkalinization with NaHCO3 were evaluated. Major morbidity and mortality were recorded for all patients. Hypotension was corrected within 1 hour in 20 of 21 (96%) patients, QRS prolongation corrected in 39 of 49 (80%), and mental status improved in 40 of 85 (47%). There was one death, in a patient who was moribund on arrival to the EMC. No complications were attributable to the administration of NaHCO3. NaHCO3 seems to improve hypotension and normalize QRS duration rapidly in most patients treated, and improve mental status changes in almost one half. Serum alkalinization with NaHCO3, in conjunction with appropriate supportive care, seems to limit major morbidity and mortality effectively in patients with serious CA overdose. PMID- 8216513 TI - Emergency department ultrasound in the evaluation of blunt abdominal trauma. AB - The main objective of this study was to compare bedside sonographic detection of hemoperitoneum with diagnostic peritoneal lavage/laparotomy in the patient with blunt abdominal trauma. A retrospective review was conducted of all blunt trauma patients that underwent emergency department (bedside) sonography to rule out intraperitoneal hemorrhage at a level I trauma center in 1991 to 1992. Patients were included in the study population only if: (1) the results of the ultrasound examination were interpreted before any other diagnostic studies, and (2) a diagnostic peritoneal lavage (DPL) or laparotomy was performed. The ultrasound examination consisted of a single right inter/subcostal longitudinal view with the patient in the trendelenburg position performed by the emergency physician or surgeon. A real-time sector scanner with a 3.5 MHz probe was used. The presence of an anechoic (black) stripe between the liver and the right kidney (Morrison's pouch) was interpreted as a positive study, and the absence of this finding was interpreted as a negative study. A positive DPL was defined as > or = 10 mL of gross blood or a blood cell count > or = 100,000/mm3 in the returned lavage fluid, and a positive laparotomy as > or = 100 mL of intraperitoneal blood. Forty four patients met the inclusion criteria for the study. Eleven patients (24%) in this population had either a positive DPL or laparotomy. The sensitivity, specificity, and accuracy of bedside sonography in identifying intraperitoneal hemorrhage was 81.8%, 93.9%, and 90.9%, respectively. The ultrasound study provided an answer in less than 1 minute in most patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216514 TI - Tissue and organ procurement in the emergency department setting. AB - A retrospective chart review of all emergency department (ED) deaths in patients younger than 65 years in seven area hospitals was performed for the calendar year of 1990. The number and percentage of families approached and consenting to tissue donation among the various EDs was compared and reasons for not approaching families were evaluated for their validity. Procurement rates between the years 1990 and 1991 were compared for two area hospitals, which made a specified (nonmedical) service responsible for tissue requests in 1991. There were 368 deaths, 255 of which were potential donors by acceptable criteria. Only 109 (43%) families were approached regarding tissue donation. The overall procurement rate was 12%. Suburban EDs had a higher approach and procurement rate than did urban EDs (49% vs 36%; P < .05 and 19% vs 5%; P < .01, respectively). Procurement rates for two hospitals that designated a specific procurement service in 1991 more than doubled (5% vs 11%; P = NS). Tissue procurement rates in EDs with procurement systems in place are low despite consent rates of those approached of 36%. The major contributing factor is the failure to request tissue from the families of eligible candidates even when there are no exclusion criteria met. Suburban EDs had a higher success rate than urban EDs. PMID- 8216515 TI - Angioedema in the emergency department: the impact of angiotensin-converting enzyme inhibitors. AB - Angiotensin-converting enzyme (ACE) inhibitors have been reported to cause angioedema. The purpose of this study was to establish what proportion of patients who present to the emergency department (ED) with angioedema were concomitantly taking any of the ACE inhibitors and to show how this group differed in presentation and response to treatment from the larger population of patients with non-ACE inhibitor-related angioedema. An 8-year retrospective chart review of all patients with the diagnosis of angioedema observed from January 1, 1984 to December 31, 1991 was undertaken in the ED of an urban teaching hospital. Forty-nine patients ranging from 12 to 88 years of age with symptoms and physical examination that was consistent with the diagnosis of angioedema were entered onto the study. Twelve cases of ACE inhibitor-related angioedema were identified, all occurring in the last 4 years of the review, and when compared with the non ACE inhibitor-related group were older (mean age, 63.3 vs 43.0 years), had less of an allergic history (0% vs 49%; P = .013), but demonstrated the same severity of symptoms and response to medical therapy. No case required an artificial or surgical airway. ACE inhibitor related angioedema is becoming a common type of angioedema observed in this ED. These patients are older and free of other allergic disease and respond well to traditional therapy. PMID- 8216516 TI - Superoxide dismutase with prolonged in vivo half-life inhibits intravascular hemolysis and renal injury in burned rats. AB - Although superoxide radicals and related metabolites have been postulated to underlie the pathogenesis of burn injury, critical evidence supporting this hypothesis is lacking. To test whether superoxide radicals play critical roles in burn injury, the effect of a superoxide dismutase (SOD) derivative (SM-SOD) was tested on intravascular hemolysis and renal tubular injury in rats subjected to burn shock. Within 3 hours after a given full-thickness burn of approximately 24% of body surface area, plasma levels of lipid peroxides increased significantly with concomitant increase in intravascular hemolysis. Histological examination showed a marked deposition of hemoglobin-like casts in renal tubules of the burned rats. Intravenous administration of SM-SOD (10 mg/kg) 30 minutes before the burn injury significantly inhibited the increase of plasma lipid peroxides and the occurrence of intravascular hemolysis. SM-SOD also inhibited the deposition of casts in renal tubules. These results indicate that superoxide radicals play critical roles in the pathogenesis of intravascular hemolysis and renal damage induced by burn injury. PMID- 8216517 TI - A comparison of combined amrinone and glucagon therapy to glucagon alone for cardiovascular depression associated with propranolol toxicity in a canine model. AB - Multiple inotropic agents may be required to improve hypotension associated with beta-blocker toxicity. This study compared combined amrinone and glucagon therapy to glucagon alone and saline control for the treatment of propranolol-induced cardiovascular depression in a canine model. Six animals were pretreated with 10 mg/kg of propranolol intravenously (i.v.), which resulted in significant depression in heart rate (HR), cardiac output (CO), mean arterial pressure (MAP), and maximal left ventricular change in pressure over time (dP/dt max) (P < .0001). Each canine received i.v. amrinone (4 mg/kg) plus glucagon (20 micrograms/kg) therapy during a 2-minute period after propranolol infusion was completed. Cardiovascular parameters were monitored at 1, 6, 11, 21, and 31 minutes after treatment was rendered. Results were compared with those of a previous study, consisting of six animals that received glucagon therapy alone (20 mg/kg) and six controls (normal saline only) in an identical protocol. The addition of i.v. amrinone to glucagon therapy did not increase significantly, HR, CO, stroke volume, or dP/dt max compared with glucagon alone. Total systemic peripheral resistance was reduced significantly during 31 minutes of observation after the administration of combined therapy compared with the control; glucagon alone also reduced systemic peripheral resistance at 1 and 6 minutes. At all time periods except 1 minute of observation there was a significant reduction in MAP when comparing combined therapy with that of glucagon therapy alone. In this model, the addition of amrinone to glucagon therapy seems to have a detrimental effect on the ability of glucagon to increase MAP resulting from propranolol toxicity. PMID- 8216518 TI - Demographic characteristics of full-time emergency physicians in Canada. AB - The objective of this study was to describe individual and practice characteristics of Canadian emergency physicians, and to determine if these characteristics varied with geographic region, type of certification, or method of reimbursement. The study took place in emergency departments across Canada, and all full-time physicians with certification in emergency medicine, and a random sample of Canadian Association of Emergency Physician members without certification were surveyed with a 23-item questionnaire. Descriptive statistics on individual and practice characteristics were outcome measures. Comparative statistics evaluating demographic characteristics by region, type of certification, and method of reimbursement were used. There were significant differences between responders and nonresponders based on certification (P < .001) and region of residence (P < .005). Most physicians are male (87.3%), married (83.3%), reimbursed on a fee for service basis (61%), work in teaching hospitals (65.8%), and participate in medical education (82.3%). On average physicians are 38 years of age, work of 14 shifts/month, 9 hours/shift, 11 nonclinical emergency related hours/week, and have 5 vacation weeks/year. More physicians with FRCP(EM) certification work in teaching hospitals (P < .00001), do nonclinical emergency related work (P < .0001), participate in medical education (P < .0001), and are involved in research (P < .001). There are significant differences by geographic region in gross annual salary (P < .00001), method of reimbursement (P < .00001), and independent hospital emergency department status (P < .00001). Fee-for-service reimbursement for clinical service provides a higher gross annual income than other methods (P = .028). Emergency medicine is an emerging clinical discipline with a strong academic focus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216519 TI - Assessment of the current computer literacy and future computer needs of emergency medicine residents and faculty. AB - The purpose of this study was to assess the current computer literacy and future computer needs of emergency medicine residents and faculty to aid in developing a computer literacy curriculum. All emergency medicine residents and full-time faculty from a random sample of emergency medicine residencies were mailed questionnaires assessing current computer familiarity and future computer needs. Twenty-one residencies were surveyed; 15 resident and 17 faculty questionnaires were returned. Thirty-seven percent (116 of 314) faculty and 29% (135 of 470) resident questionnaires were completed and returned. Eighty percent (12 of 15) of residencies had a designated computer for resident use; 93% (14 of 15) had a computer for use in the emergency department. Forty-seven percent of residents owned their own computer; 68% of faculty had a computer in their home, and 52% had computers in their office. Less than 30% of residents and faculty had formal computer training. Residents and faculty rated the current familiarity and future needs for various software applications on a five-point scale. Data were analyzed using the Wilcoxon-Rank Sum Test. Residents and faculty had the most anticipated need for word processing, graphics, literature searching, data base, and patient management programs. Future computer need was rated significantly higher than current computer familiarity in all computer application areas (P < or = .0002). It seems that emergency medicine residents and faculty have adequate access to computers, but minimal computer training. Residents and faculty have a high anticipated need for various basic computer applications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216520 TI - An assessment of the sensibility of a quality-of-life instrument. AB - The objective of this study was to assess the sensibility of an asthma quality-of life questionnaire (AQLQ); therefore, a structured survey of asthma patients seen in Hamilton, Ontario, emergency departments and physicians involved in asthma management was performed. Twenty-five consecutive patients who had completed the AQLQ questionnaire twice during a 7- to 10-day pilot study assessed sensibility using a 12-item questionnaire. The same number of practicing physicians from four centers in Ontario were sent the asthma AQLQ questionnaire and were asked to complete a 13-item sensibility form. All patients who were approached successfully completed the sensibility assessment; 80% (20 of 25) of the practicing physicians completed the assessment. Mean response scores were more than 5 of a possible 7 points in all questions for both groups. Patients had more mean responses greater than 6 (7 of 12) than did physicians (2 of 13). The AQLQ seems acceptable and sensible to both patients and physicians. A formal assessment of the sensibility of an outcome measurement can provide valuable information regarding it's use. Both research and clinical outcomes should be subjected to this form of evaluation. PMID- 8216521 TI - Sudden death in a young adult: sequelae of childhood Kawasaki disease. AB - A case of sudden cardiac death in a young adult secondary to sequelae of childhood Kawasaki disease is presented. At autopsy, proximal coronary artery aneurysms typical of Kawasaki disease with recent and remote myocardial infarction was found. Although the acute diagnosis and management of Kawasaki disease has received attention in recent literature, little has been written about the implications of the disease in long-term survivors. Serious morbidity and mortality many years after the acute phase of the disease can occur. Because of the relatively recent recognition of the disease, an undetermined population of patients with previously unrecognized Kawasaki disease exists. Young patients with previous Kawasaki disease may have severe stenotic coronary disease that may be asymptomatic and present with sudden cardiovascular symptoms or death. Acute care physicians should be cognizant of these issues and should seek specific information regarding childhood illnesses when evaluating the young patient with acute cardiovascular symptoms. PMID- 8216522 TI - Personal computer teleradiology: comparing image quality of lateral cervical spine radiographs with conventional teleradiology. AB - Teleradiology images of 14 cervical spine x-rays were studied by radiologists to compare radiological diagnostic interpretations and image quality with an inexpensive personal computer (PC) teleradiology system adapted to personal computers. Image quality ratings were similar for the conventional teleradiology images, PC teleradiology images, and the original cervical spine films. Interpretations of images showed some variation between PC and conventional teleradiology. Lesions in poorly contrasted films were visible with difficulty, using PC teleradiology. Lesions in well-contrasted films were identified easily with all three image types. Inexpensive teleradiology can be achieved using PC devices already on the market for $650 to $2000 compared with $30,000 for conventional teleradiology. Standardization of image and modem transmission parameters may facilitate the development of interhospital image transfers to optimize patient transfers and to assist in long-distance patient consultations. PC teleradiology deserves further study. PMID- 8216523 TI - Multiple trauma in the achondroplastic dwarf: an emergency medicine physician perspective case report and literature review. AB - Although uncommon, the achondroplastic dwarf (AD) may become the victim of multiple trauma, presenting special challenges for the emergency department (ED) physician. Traditional management of airway, breathing, circulation, and neurological disability is altered by the unique anatomic features of achondroplasia. Despite facial abnormalities observed in the AD, orotracheal and nasotracheal intubation are usually accomplished without particular difficulty; however, abnormalities of the base of the skull and cervical spine make hyperextension of the neck especially hazardous in these patients. The lungs are functionally normal, although vital capacity is decreased and thoracic case abnormalities and abdominal obesity impair lung expansion. Vascular access in the AD is difficult. Peripheral access is difficult because of excessive subcutaneous fat, whereas central venous access is complicated by neck, chest wall, and spinal abnormalities that obscure commonly used anatomic landmarks. Major neurological syndromes observed in ADs are hydrocephalus, cervical medullary compression, and thoracolumbar stenosis. The ED physician should recognize these syndromes, their potential to produce neurological disability, and their unique implications for trauma. PMID- 8216524 TI - Occult penetrating orbital trauma. AB - The case of a 25-year-old male college student who presented to the emergency department with uniocular blindness is described. Initially, the injury was thought to be secondary to blunt orbital trauma. Further investigation showed an occult gunshot wound to the orbit. The diagnosis and management of penetrating orbital trauma are discussed. PMID- 8216525 TI - Hysterical stridor: a diagnosis of exclusion. AB - Two stridorous patients who presented to the emergency department with respiratory distress are discussed. Thorough history, physical examination, and direct visualization of the larynx failed to detect any anatomical upper airway abnormalities; therefore, the etiology of airway obstruction in both patients was determined to be psychogenic. Stridor caused by psychogenic causes is uncommon and, probably, underrecognized. Stridor caused by structural and pathological causes must be considered and excluded before it can be attributed to psychogenic causes, thereby making this a diagnosis of exclusion. PMID- 8216526 TI - Recognition of electrocardiographic lead misplacements. AB - Improper placement of recording electrodes on the skin can generate misleading patterns on the electrocardiogram (ECG). The alterations in the normal ECG caused by lead misplacement were reviewed. Although most clinicians can recognize the common right arm/left arm lead switch that imitates a nonsinus atrial rhythm with high anterolateral myocardial infarction, many other errors are possible. Less common lead placement errors are often difficult to detect. Exchanging the right arm and left leg leads creates what seems to be an inferior wall myocardial infarction and a nonsinus atrial rhythm in normal patients. Reversal of the right arm and right leg connections creates a unique pattern of diffuse low voltage in the limb leads. Precordial lead switches are common and can be recognized by the abnormal R wave progression that is created. PMID- 8216527 TI - Trauma: an annotated bibliography of the recent literature. PMID- 8216528 TI - High-dose epinephrine. PMID- 8216529 TI - Emergency medicine as primary care? PMID- 8216530 TI - The rape of emergency medicine revisited. PMID- 8216531 TI - Mental stress and acute myocardial infarction. PMID- 8216532 TI - Red labels for industrial-strength magnesium. PMID- 8216533 TI - Use of diagnostic radiographs for ED trauma. PMID- 8216534 TI - Computed tomography findings of an intraorbital pencil. PMID- 8216535 TI - The comparative sensitivity and specificity of serum and urine HCG determinations in the ED. PMID- 8216536 TI - Hyperbaric oxygen therapy. PMID- 8216537 TI - Carbohydrate-deficient glycoprotein syndromes: peculiar group of new disorders. AB - A new group of metabolic disorders, the carbohydrate-deficient glycoprotein (CDG) syndromes, is reviewed with emphasis on the key condition, the CDG syndrome type I. This disease, an autosomal-recessive multisystem condition, has now been diagnosed in 45 Scandinavian patients. It is characterized by carbohydrate deficiencies of a number of glycoproteins, including uniform changes in transferrin. The transferrin alterations provide a distinct biologic marker and a practical and simple laboratory diagnostic means employing analysis of serum or blood spots from Guthrie-type filter paper. The syndrome presents differently through various life periods. A four-stage grouping system by age has been constructed and is presented. During infancy, internal organ symptoms are dominant; some may be life-threatening. In later childhood and adolescence, static mental deficiency, cerebellar ataxia, slowly progressive lower limb neuropathy, and pigmentary retinal degeneration, as well as secondary skeletal deformities, are the most prominent findings. Two very recently described clinical and biologic variants, CDG syndromes II and III, are summarized and compared to CDG type I. PMID- 8216538 TI - Autonomic nervous system function in severe breath-holding spells. AB - This study attempted to determine noninvasively whether a dysregulation of autonomic nervous system reflexes exists in children with severe cyanotic breath holding spells (BHS). This was a cross-sectional study performed in the neurophysiology laboratory at a tertiary care hospital. Patients, 18 months of age and older taken from a referral population of children with severe cyanotic BHS and normal controls, were studied. Fourteen children with cyanotic BHS and 12 controls were evaluated. Several noninvasive measures of parasympathetic and sympathetic reflex functions were assessed and statistically analyzed using analysis of variance and covariance, and Fisher's exact tests. The cyanotic BHS group had a significantly greater increase in pulse rate at 15 s of standing after rising from the supine position (P < .06), with a trend toward a concomitant higher mean arterial pressure (P < .09). After adjusting for age, sex, and mean supine systolic and diastolic blood pressures, breath-holders had a greater decrease in diastolic blood pressure (P < .02) without an increase in systolic blood pressure after standing from the supine position. Breath-holders also had significantly abnormal 30:15 R-R interval ratios compared with controls (P < .002). These results support the hypothesis that children with cyanotic BHS have underlying autonomic nervous system dysregulation. This dysregulation may contribute to the pathophysiology of severe BHS in these children. PMID- 8216539 TI - Severe fetal acidemia: neonatal neurologic features and short-term outcome. AB - The objectives of this study were to determine if infants delivered with severe acidemia (cord umbilical arterial pH < 7.0) had short-term neurologic effects and whether infants with persistent bradycardia who received cardiopulmonary resuscitation (CPR) in the delivery room would be at greatest risk for subsequently developing neonatal seizures. Forty-seven infants (39 term, 8 preterm) delivered with severe fetal acidemia were studied. The mean (+/- S.D.) for pH, PaCO2, and base deficit for the 47 infants was 6.86 +/- 0.11, 97 +/- 22 mm Hg, and -17 +/- 4, respectively. Labor complications were common and included placental abruption in 8, ruptured uterus in 4, cord prolapse in 3, fetal heart rate decelerations in 12, and other (n = 14). Most infants were delivered via emergency cesarean section (n = 29). Delivery room interventions included oxygen and bag/mask ventilation only (n = 20) and intubation and ventilation (n = 22); 7 of 22 infants received CPR and epinephrine for persistent bradycardia (heart rate < 80 beats/min despite ventilatory support). Five infants required no intervention. Eight infants (17%) had seizures; 6 of these infants received CPR in the delivery room. Short-term outcomes were abnormal in 7 of 8 infants (i.e., death in 5, abnormal neurologic examination at discharge in 2). In 39 infants without seizures, 32 had transient neurologic abnormalities (i.e., irritability, hyperreflexia, proximal hypotonia) which resolved by discharge, and 2 had abnormal and 5 normal examinations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216540 TI - Sturge-Weber syndrome: study of 40 patients. AB - Forty patients with Sturge-Weber syndrome were studied over a 26-year period. The nevus flammeus was unilateral in 27 patients (twice as often on left side) and bilateral in 13 patients. Only 3 of these 13 patients had bilateral cerebral lesions. Seizures, most of which were focal, were present in 32 patients (80%). The percentage of patients in whom the seizures subsequently became generalized was very high. Seizure presentation coincided with febrile episodes in 10 of 32 patients (31%). Total seizure control was obtained in 15 patients (47%). Abnormality of the cerebral parenchyma can be detected from birth in some patients and has a progressive character; at the same time, progressive atrophy and parenchymatous hyperdensity of the affected hemisphere is evident, as well as a decrease in arterial size, especially during the first decade of life. No relationship exists between the size of the facial nevus flammeus or its unilateral or bilateral location and clinical neurologic impairment. Conversely, a direct relationship exists between greater anatomic manifestations (i.e., atrophy, calcification) in the involved hemisphere when the lesion is unilateral as well as the presence of leptomeningeal angiomatosis in both cerebral hemispheres in patients with bilateral facial nevus flammeus and the severity of clinical disorders. Mental retardation was present in 60% of patients and was severe in 32.5% of all patients. Even though computed tomography and T1- and T2 weighted magnetic resonance imaging have great diagnostic value, magnetic resonance imaging enhanced with gadolinium-DTPA discloses the cerebral, leptomeningeal, and ocular lesions before the first evidence of neurologic abnormality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216541 TI - Transient oculosympathetic paresis (group II Raeder paratrigeminal neuralgia) of childhood: migraine variant. AB - Although a recognized migrainous phenomenon in adults, transient oculosympathetic paresis in childhood has been rarely observed. Six pediatric patients are reported with transient oculosympathetic paresis occurring within the context of characteristic vascular headaches. The clinical profiles of the patients suggest transient dysfunction of third-order ocular sympathetic pathways and represent most likely a benign, self-limited variant of pediatric migrainous neuralgia. PMID- 8216542 TI - Low levels of CSF gangliotetraose-series gangliosides in West syndrome: implication of brain maturation disturbance. AB - One ml of cerebrospinal fluid (CSF) from each patient with West syndrome and patients from disease control groups were analyzed separately by highly sensitive thin-layer chromatography/enzyme-immunostaining method. The levels (mean +/- S.D.) of GM1, GD1a, sum of GD1b, GT1b, and GQ1b, and total gangliotetraose-series gangliosides in West syndrome patients (n = 14) and in an age-matched control group (n = 14) were as follows: 11.6 +/- 7.8 and 30.9 +/- 12.3 ng/ml CSF, 51.5 +/ 23.2 and 91.7 +/- 41.2 ng/ml CSF, 129.6 +/- 57.6 and 195.9 +/- 123.6 ng/ml CSF, and 192.7 +/- 78.6 and 318.4 +/- 131.6 ng/ml CSF, respectively. The differences were statistically significant except for the sum of GD1b, GT1b, and GQ1b (by 2 sample t test). Because they are abundant in the outer surface of neuronal plasma membranes, gangliosides may play an important role in the transformation of a neuroblast into a functionally mature neuron. Low levels of CSF gangliotetraose series gangliosides, especially GM1 and GD1a, in patients with West syndrome may suggest a maturation disturbance of the brain from an early developmental stage. PMID- 8216543 TI - Normal developmental profiles of CSF gangliotetraose-series gangliosides from neonatal period to adolescence. AB - The normal developmental profiles of cerebrospinal fluid (CSF) gangliosides were examined from the neonatal period to adolescence, using 1 ml of clinically available CSF, by the thin-layer chromatography/enzyme-immunostaining method. The level of total gangliotetraose-series gangliosides, including GM1, GD1a, GT1a, GD1b, GT1b, and GQ1b, increased 3.8-fold from the neonatal period to age 5 years, followed by a plateau, and then a mild decrease. The developmental profiles of individual gangliosides differed from each other. CSF gangliosides change with age, reflecting the maturational changes of the central nervous system gangliosides in situ. CSF ganglioside analysis and this developmental profile might be useful for examining ganglioside aberrations and basic neurochemical mechanisms underlying neurologic disorders, especially age-dependent diseases. PMID- 8216544 TI - Neurologic manifestations in familial Mediterranean fever. AB - Neurologic involvement in children with familial Mediterranean fever is relatively uncommon and rarely described in the pediatric literature. Although headaches occur frequently, meningitis and convulsions are rare. Thirteen of 101 children with familial Mediterranean fever developed neurologic manifestations. Of these 13 patients, 10 had headaches during acute episodes of the fever. Two patients had convulsions with fever before the age of 5 years; the convulsions and acute episodes recurred at ages 9 and 10 years. Another patient had two episodes of aseptic meningitis followed by convulsive disorder before the diagnosis of familial Mediterranean fever was made; his convulsions were resistant to antiepileptic drugs alone and subsided only when colchicine was added. The possibility of neurologic involvement should be considered in patients with familial Mediterranean fever. PMID- 8216546 TI - Pallister-Killian syndrome in older children and adolescents. AB - The Pallister-Killian syndrome is caused by a mosaic tetrasomy of the short arm of chromosome 12. Although analysis of peripheral blood lymphocytes usually reveals a normal karyotype, an isochromosome 12p mosaicism is detectable in fibroblast cultures; therefore, in this rare chromosomal aberration, clinical recognition is crucial for appropriate cytogenetic investigations. The phenotype of younger children has already been well documented. During childhood and adolescence, however, the phenotype changes markedly. The disorder in older children and young adults is characterized by a coarse and flat facies, macroglossia prognathia, everted lower lip, and severe psychomotor retardation with muscular hypertonia and contractures. Two severely mentally retarded patients are reported whose diagnoses were confirmed by fibroblast cultures at ages 16 and 21 years. PMID- 8216545 TI - Infantile neuroaxonal dystrophy: axonal changes in biopsied muscle tissue. AB - Dystrophic axons were found in the biopsied muscle tissue of a 17-month-old hypotonic infant after confirmation of a diagnosis of infantile neuroaxonal dystrophy (INAD) by subsequent peripheral nerve biopsy. He manifested gradual deterioration and had brief tonic seizures. The sural nerve biopsy, performed at age 42 months, confirmed INAD. Intensive ultrastructural investigation of the preceding muscle biopsy specimens demonstrated infrequent but definite findings of axonal degeneration in the musculature. Ultrastructural investigation of muscle biopsy should include a careful search for neural tissue because in INAD axonal changes occur primarily in the presynaptic region. PMID- 8216547 TI - Visual "release" hallucinations in juvenile neuronal ceroid-lipofuscinosis. AB - A child with juvenile neuronal ceroid-lipofuscinosis developed formed and unformed visual hallucinations with the development of blindness. The hallucinations lasted for prolonged periods, were of simple, varied, and novel content and were not associated with any ictal manifestations. The clinical features support a "release" mechanism for the hallucinations. PMID- 8216548 TI - Infantile galactosialidosis presenting with congenital adrenal hyperplasia and renal hypertension. AB - A patient with early infantile galactosialidosis presenting as congenital adrenal hyperplasia with clitoral hypertrophy and arterial hypertension is reported. Serum 17-alpha-OH-progesterone and plasma renin levels were elevated. Adrenal hyperplasia and thickening of the cardiac septum were detected by sonography; however, progressive hepatosplenomegaly, increasingly coarse features, and vacuolization of bone marrow and liver cells suggested a storage disorder. Combined deficiency of beta-galactosidase and sialidase enzyme activity in both lymphocytes and cultured fibroblasts was detected. This patient with early infantile galactosialidosis is the first reported who presented with congenital adrenal hyperplasia. PMID- 8216549 TI - PET of infant in persistent vegetative state. AB - This is the first report of cranial positron emission tomography findings of an infant in a persistent vegetative state. Serial positron emission tomography/2 deoxy-2[18F]fluoro-D-glucose studies demonstrated persistent global reduction of cerebral glucose metabolism, results similar to those found in adults in persistent vegetative states. Positron emission tomography may be useful in confirming this clinical diagnosis in infants. PMID- 8216550 TI - Duane retraction syndrome associated with Chiari I malformation. AB - A 13-year-old girl who had Duane retraction syndrome associated with Chiari I malformation is reported. Neuro-ophthalmologic examination revealed severe limitation of abduction of the left eye, as well as narrowing of the palpebral fissure and retraction of the globe on adduction. Electro-oculography of the affected eye revealed decreased saccadic velocity on attempted abduction and adduction. Midsagittal magnetic resonance imaging demonstrated cerebellar tonsillar herniation to 6 mm below a line from the basion to opisthion. Taking into consideration the relative rarity of the two disorders, the association may not be coincidental. Magnetic resonance imaging of the posterior fossa is recommended in Duane retraction syndrome. PMID- 8216551 TI - Controversies in treatment of neonatal seizures. PMID- 8216552 TI - Controversies in treatment of neonatal seizures. PMID- 8216553 TI - The development of immunity to malaria (a clinical view) PMID- 8216554 TI - Skin testing in patients with high risk of anaphylactic reactions to penicillin. AB - Sequential skin testing including immediate patch test (IPT), skin prick test (SPT), and intradermal test (IT) with sodium benzylpenicillin G (Pen G), and SPT with benzylpenicilloyl human serum albumin (BPO-HSA) was done in 58 subjects with a history of probable anaphylactic reaction or shock of unknown cause. Based on positive skin tests, the diagnosis of penicillin anaphylaxis was confirmed in 30 patients. The average age of onset of penicillin allergy was 42 years ranging from 20-70 years. The sex ratio was 2:28 with marked female predominance. Anaphylactic shock, wheezing and urticaria occurred in 21, 20, 19 patients, respectively. Most symptoms were induced by skin tests and inhalation. The results of skin tests in these patients showed that IPT with 500 U/ml of Pen G was not only reliable but also safe. It is suggested that patients suspected of penicillin anaphylaxis should received IPT with 500 U/ml of Pen G as the initial diagnostic step; if a negative reaction occurred, then SPT and IT should be applied with the same concentration of Pen G, until a positive reaction developed or all the skin testing showed negative results. SPT to BPO-HSA was safe, but its positive rate was only 47.8% in our study; it seems to be less important than skin test to Pen G. As a whole, the skin testing procedure we recommend is relatively reliable, safe and practical even in individuals extremely sensitive to penicillin. In addition, once the patient develops a positive IPT, Pen G residue on the testing site should be wiped away rapidly and washed out with cool water thoroughly to disrupt further violent reaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216555 TI - Survey of airborne culturable and non-culturable fungi at different sites in Delhi metropolis. AB - A two year aerobiological survey for culturable and non-culturable fungi was conducted at human height at five different sites in Delhi metropolis. Burkard Personal Volumetric Sampler for petriplates and slide exposures were used for sampling the air. With simultaneous petriplate and slide exposure a total of 98 fungal forms were recorded. Cladosporium contributed for 25-40% of total airborne fungi followed by Ustilago (smuts) (24%) Aspergillus flavus (10-13%), Alternaria (11%) and A. niger (8%). Basidiomycetes contributed 7-13% at different sites. The frequency of occurrence of these types varied from 50-98%. In general fungal concentration was high from July to April with low counts in winter (January) and dry and hot summer (May-June). Quantitative variations in the spore counts were found to be statistically significant within the same urban locality. PMID- 8216556 TI - Quality assurance of immunodiagnostic tests in Australia: II. Five year review. AB - A Royal College of Pathologists of Australasia (RCPA) sponsored quality assurance program in clinical immunopathology has, over a 5 year period, demonstrated: enrollment by the majority of immunodiagnostic laboratories in Australia and New Zealand; improved compliance with the program over time eg. increasing numbers returning their replies by the due date; different commercial techniques give different mean values for the same analyte. This appears to be due to the use of different reference materials in each technique; greater utilization of nephelometric techniques in quantitating immunoglobulins, C3, C4, CRP and rheumatoid factor resulting in better accuracy and precision; improvement in the frequency of detecting anticentromere antibody as most laboratories use proliferating cell lines as substrate for anti-nuclear antibody (ANA) detection; improved interlaboratory concordance of ANA titers by the provision of reference standards; improved detection of antibodies to extractable nuclear antigens (counter-immunoelectrophoresis being more sensitive than immunodiffusion); the Farr and radioimmunoassay technique for the demonstration of antibodies to native DNA have greater sensitivity than the Crithidia assay; improvement in accuracy and precision of cell phenotype analysis with the use of whole blood and cell flow cytometric techniques; development of techniques to rank each laboratories performance on a rating scale based on the average number of tests outliers (from the consensus mean) per mailing. However deficiencies in performance are still being observed. These relate to both technical factors causing systematic errors and in the provision of interpretive comments on the laboratory result. Continuing education and participation in quality assurance programs are emphasized to monitor and improve performance over time. PMID- 8216557 TI - Prevalence of IgA specific antibodies to Epstein-Barr virus capsid and early antigens in nasopharyngeal carcinoma. AB - Ninety-one patients with nasopharyngeal carcinoma (NPC), and 164 age-matched healthy controls were tested for presence of IgA antibodies to Epstein-Barr virus capsid antigen (VCA) and early antigen (EA) in their sera by indirect ELISA using "EBViral DETECT" commercial test kit. IgA anti-VCA was found in 76 (83.5%) of NPC patients and 16 (9.8%) of the controls. Meanwhile, IgA anti-EA was found in 72 (79.1%) of NPC patients and 21 (12.8%) of the controls. In a parallel study by indirect immunofluorescence test (IIF), IgA anti-VCA was found in 77 of 91 (84.6%) NPC patients and 22 of 142 (15.5%) controls. The prevalence rates of anti VCA as screened by ELISA and IIF were very similar suggesting that neither one of the two tests can be used alternatively depending on the purpose and facilities in each individual laboratory. IgA antibodies to VCA and EA were more prevalence in NPC patients than those in the controls, the finding which again supported the association between EBV and NPC as was suggested in many other reports. PMID- 8216558 TI - Detection of antibodies against Salmonella typhi outer membrane protein (OMP) preparation in typhoid fever patients. AB - An indirect ELISA was used to detect antibodies against outer membrane protein preparations (OMPs) from Salmonella typhi. Sera from patients with a definitive diagnosis of typhoid fever (TF) gave a mean absorbance reading, at 414 nm, of 1.52 +/- 0.23 as compared to 0.30 +/- 0.11 for sera from healthy individuals. This gave a positive to negative ratio of absorbance readings of approximately 5.1. Suspected TF patients (no isolation of S. typhi), with positive and negative Widal titers had mean absorbance readings of 1.282 +/00.46 and 0.25 +/- 0.19, respectively. Sera from patients with leptospirosis, rickettsial typhus, dengue fever, and other infections gave mean absorbances of 0.20 +/- 0.08, 0.24 +/- 0.08, 0.27 +/- 0.08, and 0.31 +/- 0.16, respectively. The sensitivity, specificity, positive and negative predictive values were 100%, 94%, 80% and 100%, respectively. The antibody response detected in the definitive TF cases was predominantly IgG in nature and no cross-reactivity was seen with OMP preparations extracted from E. coli. Variable reactivity was noted with OMP preparations obtained from other Salmonella spp. Three major OMPs are presented in the antigen preparation and strong binding of positive sera was detected to all three bands. PMID- 8216559 TI - Enhanced eosinophil luminol-dependent chemiluminescence and complement receptor expression by platelet-activating factor and interleukin-5. AB - The cytokine interleukin-5 (IL-5) and the lipid mediator platelet-activating factor (PAF) have both been shown to be involved in eosinophil differentiation and activation. We have measured and compared the effect of PAF and IL-5 on human eosinophils in terms of their luminol-dependent chemiluminescence (CL) response and their expression of complement receptors, CR1 and CR3. Both IL-5 and PAF enhanced the eosinophil CL response. The optimal concentrations were 40 U/ml for IL-5, and 10(-6) M for PAF. The priming effect of IL-5 was slow and reached a maximal response after 90 minutes incubation. In contrast, the effect of PAF peaked early and declined during incubation. In the complement receptor study, only PAF was able to enhance CR3 expression (p < 0.05) while the effect of IL-5 on eosinophil complement receptor expression was negligible. These results provide evidence that both inflammatory mediator (PAF) and cytokine (IL-5) can activate eosinophils but the effects of IL-5 and PAF on eosinophil CL response appear to be distinct. The activation of eosinophils by PAF and IL-5 may occur through different mechanisms. PMID- 8216560 TI - Production of monoclonal antibodies to Vi polysaccharide antigen of Salmonella typhi. AB - Twenty-four Vi antigen-specific monoclonal antibodies were produced in this study. The MAbs were found to be highly specific to Vi possessing bacteria. Selected MAbs were used in a direct agglutination assay for rapid identification of S. typhi in primary bacterial culture and also used to develop an assay to detect Vi antigen in clinical specimens. The result showed that they could not detect the antigen in urine and serum from acute patients even they could detect as low as 0.02 micrograms/ml of Vi antigen added in normal urine. The study has shown that these MAbs are very useful for rapid identification of S. typhi in primary bacterial culture and they can replace polyclonal anti-Vi antibodies which have been used routinely in bacteriological laboratories. PMID- 8216561 TI - Molecular cloning and expression of Salmonella typhi flagellin: characterization of 52 kDa specific antigen of S. typhi. AB - We previously reported monoclonal antibodies (MAbs) specific to S. typhi 52 kDa antigen which do not cross react with related protein antigens from 11 bacteria causing enteric fever and enteric fever-like illness. Using the combination of these specific MAbs and recombinant DNA technology, expression plasmids containing the antigen gene producing substantial amount of the S. typhi protein antigen have been established. Plasmid pSKM-T7 containing the specific 52 kDa antigen gene was cloned and the antigen expressed was detectable by immunoblotting using specific mAbs. The complete nucleotide sequence of this gene was compared with other bacterial sequences and found to be highly homologous with the flagellin gene H1-d of S. muenchen except in the hypervariable region in the central portion. The specific 52 kDa antigen of S. typhi detected by our MAbs is thus a flagellin. PMID- 8216562 TI - Comparison of the protective efficacy on mekongi schistosomiasis in mice induced by antigens derived from cercariae, schistosomulae and adult worms. AB - Protective efficacy of the extracts of cercariae, schistosomulae and adult worms of S. mekongi was studied in mice receiving immunizations with these extracts emulsified with Freund's complete adjuvant initially and incomplete adjuvant subsequently, and compared with mice receiving physiological saline with or without adjuvants as controls. After challenge with cercariae, the animals were sacrificed and the larvae or adult worms harvested by lung recovery and perfusion techniques on day 5 and weeks 6-8, respectively. Worm reduction rates were significantly higher in mice receiving extracts of schistosomula (59%) and adult worms (51%) than in those receiving the cercarial extracts (31%). Similar findings were obtained with the perfusion technique showing worm reduction rates of 57%, 53% and 30% in mice receiving extracts of schistosomulae, adult worms and cercariae, respectively. ELISA antibody titers were correspondingly increased in mice receiving extracts of schistosomulae and adult worms, but not in those receiving cercariae. This apparent association may be inadequate to suggest that the increase in ELISA titer be used as an indicator for resistance in mekongi schistosomiasis. PMID- 8216563 TI - Immunogenicity of low dose Japanese encephalitis vaccine (BIKEN) administered by the intradermal route: preliminary data. AB - Two hundred twenty-four immune and non-immune adults were systematically assigned to receive a single dose of Nakayama strain JEVAC in one of four study "arms": 0.1 ml ID, 0.2 ml ID (injection of 0.1 ml at two sites), 0.3 ml ID (injection of 0.1 ml at three sites), or 1.0 ml SC. Immune responses after this single dose (in many cases "booster") was assumed to reflect immune responses of a primary series and was assessed qualitatively (percent seroconvertion) and quantitatively (geometric mean titer) a 30 and 90 days post immunization. The results showed that JEVAC given 0.1 ml. ID at two sites is likely to be as immunogenic as 1.0 ml. given SC. PMID- 8216564 TI - Immunogenicity and efficacy of a recombinant DNA hepatitis B vaccine, GenHevac B Pasteur in high risk neonates, school children and healthy adults. AB - The immunogenicity and the protective efficacy of a recombinant DNA hepatitis B vaccine, GenHevac B Pasteur with or without passive immunization with hepatitis B immunoglobulin (HBIG) in high risk neonates born from HBsAg and HBeAg positive mothers was evaluated. Twenty-six neonates (group A) received HBIG 100 IU intramuscularly at birth plus GenHevac B Pasteur 20 micrograms at birth, 1, 2 and 12 months of age while another 23 neonates (group B) received only GenHevac B Pasteur vaccine. Forty high risk newborns who received no immunization served as control group. It was found that at months 4, 12, 13 and 24 the seroconversion rate in both group A and B were very high in the range of 95-100% with the GMT ranging from 10-160,000 mlU/ml. In the control group of infants, 85% had HBsAg positive at one year of age but it was only 3.8% and 8.7% in vaccinated groups A and B, respectively. The protective efficacy in neonates group A and B were 95.5% and 89.8% at one year, respectively, with no statistically significant difference. In 46 normal school children (group C) and 48 healthy adults (group D) who received the same dose of GenHevac B Pasteur the seroconversion rates at month 4 after receiving 3 doses of vaccination were 97.8% and 83.3% in group C and group D, respectively. At month 12, the seroconversion rate in group C rose to 100% and was significantly higher than the 89.6% of group D.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216565 TI - Aerobiology of common environmental allergens: sizes of allergen carrying particles. PMID- 8216566 TI - Arthroscopic versus open Bankart procedures: a comparison of early morbidity and complications. AB - Morgan recently reported excellent results by arthroscopically suturing detached labra to the glenoid via drill holes in anterior shoulder dislocators. We attempted to quantitatively compare the operative time, and perioperative morbidity employing this technique to these same parameters using the open Bankart procedure. We retrospectively reviewed the records of consecutive patients undergoing either of these procedures at our institution over the past 2 years. Only those cases wherein the labra were reattached to the glenoid via drill holes were considered. There were 20 patients in the arthroscopic and 18 in the open Bankart groups. Using the arthroscopic method, there was a 1.8-fold decrease in operative time, a 10-fold decrease in blood loss, and a 2.5-fold decrease in postoperative narcotic use compared with the open procedure (p < 0.001). Postoperative fevers were similarly reduced. Hospital stay averaged 3.1 days with the open procedure compared with 1.1 days with the arthroscopic method (p < 0.001). Most arthroscopic Bankarts are now performed on a same-day basis. Time lost from work was 25.5 and 15.3 days for the open and arthroscopic procedures, respectively (p < 0.001). There were three complications among the patients treated with the open technique compared with none in the arthroscopic group. Thus, we conclude that the arthroscopic Bankart procedure offers significant improvements in operative time, perioperative morbidity, and complications compared with the open technique for patients with anterior shoulder instability. PMID- 8216567 TI - The clinical effect of naproxen sodium after arthroscopy of the knee: a randomized, double-blind, prospective study. AB - The aim of this study was to examine the clinical effect of naproxen sodium after knee arthroscopy. The design was randomized, prospective, and double-blind, with a placebo control group. Patients with preoperative synovial reaction were excluded. One hundred twenty consecutive arthroscopies were performed in 77 men and 43 women, median age 34 (range 18-65) years. General anesthesia was used. Ninety-one arthroscopies were operative, whereas 29 were diagnostic. Postoperatively the patients received either 550 mg naproxen sodium twice daily or placebo for 10 days. Patients were given 500 mg acetaminophen to use if needed. Clinical examinations were performed 10 and 20 days postoperation. The results were analyzed using the Mann-Whitney test and chi 2 test. No operative complications were registered. All but two patients completed the study. Six patients had slight gastrointestinal symptoms. At 10 days' follow-up, in patients who had undergone operative arthroscopy naproxen sodium demonstrated a statistically significant effect on synovial effusion (p < 0.01), range of motion (p < 0.001), quadriceps strength (p < 0.05), pain (p < 0.001), walking activity (p < 0.05), and use of crutches (p < 0.01). In patients who had undergone diagnostic arthroscopy naproxen sodium demonstrated a beneficial effect on pain (p < 0.01). At 20 days' follow-up, in the operative group naproxen sodium affected synovial effusion (p < 0.05), range of motion (p < 0.01) and pain (p < 0.05), and walking activity (p < 0.05). No effect was seen in the diagnostic group at 20 days' follow-up. PMID- 8216568 TI - Incidental Guyon's canal release during attempted endoscopic carpal tunnel release: an anatomical study and report of two cases. AB - Two patients were found to have a partial release of Guyon's canal after attempted endoscopic carpal tunnel release. This resulted in significant morbidity from ulnar nerve injury and required open neurolysis of the ulnar nerve and carpal tunnel release. In order to determine how this error could be made, we performed an endoscopic carpal tunnel release on two cadaveric specimens with subsequent dissection, and found that Guyon's canal could be entered with relative ease through the standard portals. If, however, one is aware of this potential complication, uses the ulnar bursa overlying the flexor tendons as a guide, and makes a positive identification of the transverse fibers of the transverse carpal ligament, this mistake can be avoided. PMID- 8216569 TI - Arthroscopic and histologic evaluation of anterior cruciate ligaments reconstructed with the Leeds-Keio ligament. AB - In 62 of the patients who underwent anterior cruciate ligament (ACL) reconstruction with the Leeds-Keio (L-K) artificial ligament, we performed an arthroscopic second look and biopsy of the reconstructed ACL at 8-36 months postoperatively. Arthroscopic findings were classified into two groups according to the tautness of the ligament and the coverage of the implanted L-K ligament with synovial tissue. Histologic results were classified into three groups according to the orientation of the collagen fibers around the L-K ligament, and the arrangement and morphology of the cells. Although our results demonstrated that the implanted L-K ligament had the capacity for tissue induction, no statistically significant correlation was observed between any two results among the arthroscopic, histologic, and clinical data. Therefore, within the time span of our experiment, we could not conclude that the L-K ligament functioned as a scaffold type of artificial ligament. More convincing results must be attained before any firm recommendation can be made for the use of the L-K ligament as a substitute ACL over the autograft or allograft. PMID- 8216570 TI - Light and electron microscopic study of remodeling and maturation process in autogenous graft for anterior cruciate ligament reconstruction. AB - We evaluated the remodeling process of autogenous patellar tendon graft for anterior cruciate ligament (ACL) reconstruction by means of light microscopic (LM) and electron microscopic (EM) examinations from the biopsy specimens obtained at the time of second-look arthroscopy. Twenty-one patients were examined at various times postoperatively (from 6 weeks to 15 months, mean 9.5 months), and the results were correlated with the morphology of normal patellar tendon and normal ACL. Our study showed that the graft was revascularized in the early postoperative period, fibroblastic remodeling took place, and the graft obtained gross similarity to the original ACL on their arthroscopic and LM appearances at approximately 1 year postoperatively. However, EM study showed that at both approximately 6 months and 1 year postoperatively the grafts consisted equally of active fibroblasts with a higher cytoplasm-to-nucleus ratio compared with normal ACL. Collagen fibrils of these grafts were of uniformly small diameter compared with normal patellar tendon and ACL. Our results with ultrastructural study suggest that the grafts were still immature even at 1 year postoperatively. PMID- 8216571 TI - Intraarticular pressure of the shoulder. AB - Nine fresh frozen cadaveric shoulders were used to examine the changes in intraarticular pressure (IAP) of the shoulder joint and the position of the humeral head under various loads to determine the relationship between these parameters. All the soft tissues superficial to the rotator cuff were removed. The position of the humerus relative to the scapula was monitored using an electromagnetic tracking system before and after venting the capsule with 0, 0.5, and 1.0 kg of load applied to the humerus inferiorly in addition to the weight of the arm. Simultaneously, the IAP was monitored using a pressure transducer before venting the capsule. Venting had a significant effect on the position of the humeral head: the positions of the head after venting were significantly lowered in all loading conditions. The average IAP was -76 cm H2O without load, and the value decreased in a linear fashion with increased load; the correlations were significant in four of six shoulders without dislocation. The correlations were less significant between the pressure and the position, and there were no significant correlations between the load and the position. IAP, which is determined primarily by the load applied, is important to stabilize the shoulder inferiorly. Because IAP is intimately related to the external load and the response is specific to individuals, examination of IAP response to external load may be helpful in characterizing various instabilities of the shoulder. PMID- 8216572 TI - Arthroscopic management of septic arthritis of the hip. AB - Four patients with septic arthritis of the hip and one with suspected septic arthritis were treated with arthroscopic irrigation, debridement, and drainage. Follow-up averaged 20.4 months. Arthroscopic treatment of septic arthritis of the hip is as effective as open arthrotomy, yet with much lower morbidity. PMID- 8216573 TI - Biomechanical evaluation of interference screw fixation in a bovine patellar bone tendon-bone autograft complex for anterior cruciate ligament reconstruction. AB - A bovine model was developed for biomechanical evaluation of anterior cruciate ligament (ACL) reconstruction using patellar bone-tendon-bone (b-t-b) autograft to examine the differences in time zero fixation mechanical properties of different interference screw lengths and diameters. The surgical technique of interference screw fixation of the b-t-b complex performed clinically was reproduced in a controlled animal model. The femur-patellar tendon graft-tibia complex was tested with anterior displacement of the tibia in 30 degrees of knee flexion to allow examination of the femoral and tibial fixation properties simultaneously. The statistical model concurrently explored differences between screw length and diameter while accounting for variations between graft properties. No statistically significant differences were found between the 7- and 9-mm screws with respect to peak load or energy to failure when using a 10-mm triangular graft in a 10-mm tunnel. The 7- and 9-mm screws were superior to the 5.5-mm screws with respect to these same parameters. Based on our results, the 7 mm interference screws can be used with equal confidence as the 9-mm screw, and the 20-mm length can be similarly exchanged for 30-mm length for patellar b-t-b graft fixation. PMID- 8216574 TI - Effect of irrigation fluids on the articular cartilage: a scanning electron microscope study. AB - Four irrigation solutions, two for general arthroscopic examination and two for electrosurgery, were evaluated for their effects on the ultrastructure of the articular cartilage surface using an animal model with a scanning electron microscope (SEM). The murine knee joints were irrigated continuously for 1 or 2 h with normal saline, Ringer's lactate, 3% sorbitol, or distilled water, respectively. The articular cartilage of the patella was evaluated in situ; that is, the cartilage was kept intact as it related to the underlying bone tissue, so that artifacts during the biopsy procedure could be prevented. Results of the study showed no significant differences among the four solutions and the unirrigated control group. We conclude that Ringer's lactate, normal saline, distilled water, and 3% sorbitol can all be safely used as irrigation solutions in arthroscopic surgery. PMID- 8216575 TI - The effect of meniscal status on knee stability and function after anterior cruciate ligament reconstruction. AB - The purpose of this study was to examine the relationship of meniscal status at the time of anterior cruciate ligament (ACL) reconstruction with the ultimate function and stability of the knee joint. Seventy-one patients were studied prospectively following bone-patellar tendon-bone ACL reconstruction. Subjects were divided into six subgroups relative to the integrity (intact, partial meniscectomy, complete meniscectomy) of the two menisci. After a minimum of 2 years of follow-up (range 2-4.1 years), 56 subjects were available for subjective, objective, and radiographic assessment. Meniscal status at the time of ACL reconstruction proved to have no significant bearing on the ultimate stability of the knee. However, individuals who had undergone meniscal excision reported subjective complaints and activity limitations more commonly than those with intact menisci (p < 0.05). Radiographic changes also were more common in the meniscectomized subset. PMID- 8216576 TI - The effects of non-weight-bearing and limited motion on the tensile properties of the meniscus. AB - Recent clinical studies have suggested that many of the complications of prolonged immobilization after knee surgery can be prevented by permitting early motion while minimizing loading of healing tissues. The purpose of this study was to determine the effects of such a regimen on the tensile properties of the meniscus. The right knee of 10 skeletally mature sheep received a sham operation after which the hindlimb was placed in a harness that prevented weight bearing while permitting limited knee motion. The left knee served as the nonoperated control. Twelve weeks after surgery, paired specimens from the medial meniscus of each limb were tested in tension with the load parallel to the circumferentially oriented collagen fibers. No significant differences in the modulus, tensile strength, and ultimate strain between treated and control medial menisci were identified. Our data thus suggest that preventing weight bearing while permitting even limited motion of the knee will prevent any detrimental effect on the tensile properties of the meniscus in the circumferential direction. PMID- 8216577 TI - Comminuted tibial eminence anterior cruciate ligament avulsion fractures: failure of arthroscopic treatment. AB - Multisuture arthroscopic repair of two comminuted tibial eminence anterior cruciate ligament avulsion fractures in adult patients is reported. Lack of rigid fixation and a tentative rehabilitation program resulted in arthrofibrosis and limited knee motion. PMID- 8216578 TI - Trephination of incomplete meniscal tears. AB - The meniscus performs several roles that are important to the function of the knee joint. In an effort to preserve these functions of the meniscus, methods to promote the healing of meniscal lesions have been investigated. One such method involves trephination or the creation of vascular access channels by removal of a core of tissue from the periphery of the meniscus to the tear, thus connecting a lesion in the avascular portion of the meniscus to the peripheral blood supply. The purpose of this study is to describe our experience with arthroscopic trephination of symptomatic incomplete meniscal tears in humans. This is a simple technique that avoids the risk associated with suture repair of the meniscal tissue, yet preserves the meniscus. Overall results were good or excellent in 90% of the cases. In conclusion, symptomatic incomplete meniscal tears can be treated by stimulation of vascular channels without the risk associated with suturing of this tissue, while preserving the important functions of the meniscus. PMID- 8216579 TI - Arthroscopic treatment of triplane fractures of the ankle. AB - Failure to obtain and/or maintain adequate closed reduction of triplane ankle fractures is an indication for surgical reduction and internal fixation. Operative treatment requires anteromedial and/or anterolateral incisions for adequate visualization of fracture fragments. The added surgical trauma associated with operative treatment of these fractures can be minimized without loss of efficacy using minimally invasive techniques under arthroscopic control. Arthroscopic reduction and internal fixation (ARIF) of two-part triplane fractures provides the advantages of complete evacuation of fracture hemarthrosis, accurate and certain reduction of the articular surface, and secure fixation of fracture fragments. Two patients treated with ARIF demonstrated rapid and complete fracture healing without complication. Follow-up at 6-12 months showed no leg length discrepancy, angulation, swelling, persistent symptoms, or limitation of function. ARIF of triplane ankle fractures reduces surgical trauma, provides a method for accurate delineation of fracture fragment orientation, and ensures accurate reduction and joint congruity under direct visualization. PMID- 8216580 TI - Intraarticular hemangioma of the knee. AB - Intraarticular hemangioma is a rare cause of knee pain and effusion. The presentation of unexplained recurrent hemearthrosis associated with no or minimal trauma, skin manifestations of hemangioma, and radiographic and magnetic resonance imaging study results should alert the clinician of this unusual entity. Successful arthroscopic ablation is reported with the use of the holmium:yttrium-aluminum-garnet (YAG) laser. PMID- 8216581 TI - Arthroscopic management of tibial plateau fractures. AB - We report our initial experience with the arthroscopic management of tibial plateau fractures. The known benefits of arthroscopy include better evaluation of the entire joint, limited dissection, and thorough irrigation. We have maximized the potential of arthroscopy through the use of additional instrumentation. With this technique, arthroscopy is used as an operative tool, with the addition of instruments previously used only for ligamentous reconstruction. Some tibial plateau fractures can be treated exclusively arthroscopically, obviating the wide surgical exposures that commonly increase morbidity in these cases. PMID- 8216582 TI - A modified outside-in meniscal repair technique. AB - A modified Outside-in meniscal repair technique is described. This technique is simple, reliable and safe. PMID- 8216583 TI - How well do doctors resuscitate patients with haemorrhagic shock? AB - Patients with haemorrhagic shock of all degrees present to accident and emergency (A&E) departments regularly. This study examined 43 such patients who presented to one department over a 14-week period. The adequacy of their fluid replacement was judged in comparison with Advanced Trauma Life Support (ATLS) recommendations according to the degree of shock they appeared to have on presentation. The study found that more training may be required on the appropriate recognition and treatment of haemorrhagic shock. PMID- 8216584 TI - Skull X-ray after head injury: the recommendations of the Royal College of Surgeons Working Party report in practice. AB - In 1986 a Royal College of Surgeons Working Party published guidelines, based on over 15 years of clinical research both here and in the U.S.A., on when to perform skull X-rays on a head injury patient. In this retrospective study the recorded details of 405 patients who presented to an accident and emergency (A&E) department over a 3-month period in 1991 are analysed, and the Report criteria applied to each one to assess whether the guidelines are being followed in performing a skull X-ray. According to these guidelines, 191 of these patients (47.2%) should have been X-rayed, however, only 83 were. Only one patient was thought to have been X-rayed inappropriately. The Report criteria most commonly thought by the A&E doctors not to warrant skull X-ray, were loss of consciousness, amnesia, dizziness, blurred vision, headache, and alcohol intoxication. The reasons why these criteria are being ignored are examined, and together with reference to recent studies, slight alterations to the Working Party guidelines are suggested to make them more applicable to everyday situations of head injury encountered in a casualty department. PMID- 8216585 TI - Critical care by emergency physicians in American and English hospitals. AB - The object of this study was to compare emergency physician critical care services in an American (A) and an English (E) Emergency Department (ED). A prospective case comparison trial was used. The study was carried out at two university affiliated community hospitals, one in the U.S.A and one in England. Subjects were consecutive patients triaged as requiring critical care services and subsequently admitted to the hospital ward (A, n = 17; E, n = 18) or the intensive/critical care unit ([ICU] A, n = 14; E, n = 24). The study time period was randomly selected 8-h shifts occurring over a 4-week period. All patients were treated by standard guidelines for critical care services at the study hospital emergency department. For all study patients mean length of stay was significantly longer for the American (233 min, 95% CI 201, 264) than the English ED (24 min, 95% CI 23, 25). American emergency physicians spent less total time providing physician services (19.2 min, 95% CI 16.8, 21.6) vs. (23 min, 95% CI 21.6, 24.4) than English emergency physicians. American emergency physicians spent less time with the patient than English emergency physicians: 12.4 min (95% CI 10.3, 14.5) vs. 17 min (95% CI 15.8, 18.2). American emergency physicians spent more time on the telephone 1.8 min (95% CI 1.4, 2.2) vs. 1.2 min (95% CI 1.1, 1.3), and in patient care discussions/order giving 1.8 min (95% CI 1.4, 2.2) vs. 1.1 min (95% CI .8, 1.4), There was no significant difference in time charting (3.2 min, 95% CI 2.8, 3.6 vs. 3.5 min, 95% CI 3.2, 3.8). Results did not vary significantly whether analysed subgroups or the whole study group. American emergency physicians provided 81% of their service during the first hour. There were delays at the American hospital until the physician saw the patient: 4.9 min (95% CI 2.5, 7.3) for patients admitted to the ICU/CVU (Cardiovascular Unit), and 9.2 min (95% CI 4.6, 13.8) for patients admitted to the ward. At the American hospital, ICU/CVU physicians provided additional physician services in the emergency department whether the patient was admitted to the ward (6.7 min, 95% CI 5.5, 7.9) or the ICU/CVU (12.1 min, 95% CI 8.8, 15.9). For patients admitted to the ICU/CVU 47% of the length of stay was spent waiting for a bed to become available after the decision to admit had been made. Emergency physicians at E provided critical care services almost continuously during a short stay in the ED. Emergency physicians at A provided services intermittently with most services during an initial period of stabilization. Further study is necessary to identify what factors contribute to these different approaches to critical care in the ED. PMID- 8216586 TI - Audit of patients with chest pain presenting to an accident and emergency department over a 6-month period. AB - The results of a 6-month retrospective audit of patients presenting with chest pain to an accident and emergency (A&E) department to which 46,000 new patients per year present are discussed. The computer diagnostic code assigned to the patients by the A&E doctor, referral rates for second opinion and disposal after assessment in the A&E department are examined, with particular reference to patients who may have had serious cardiac pathology, such as acute myocardial infarction (AMI) or unstable angina. Audit showed that overall 61% of patients with chest pain of all causes were assessed and discharged home by A&E doctors without recourse to second opinion. Of patients thought by the A&E doctors to have chest pain of cardiac origin, who were referred to the duty medical registrar or cardiologist, 88% were admitted. As a result of these findings a policy of more open referral for second opinion was instituted to reduce the likelihood of discharging patients home with serious cardiac pathology. In addition, the clinical problems of AMI and unstable angina are emphasized to all senior house officers early in their educational programme after joining A&E. Published literature on the diagnosis and misdiagnosis of AMI and unstable angina in the A&E department is reviewed. These studies are almost exclusively from North America, and a need for similar work in the U.K. is discussed. PMID- 8216587 TI - Repeat deliberate self-harm: a link with childhood sexual abuse? AB - The purpose of this study was to identify whether a past history of childhood sexual abuse is a risk factor for repeated Deliberate Self-Harm (DSH). The study was a 6-month prospective study of 178 patients responsible for 190 consecutive cases of DSH seen during a 3-month censoring period. Patients were identified by review of the in-patient and accident and emergency (A&E) records of all cases of DSH at the A&E department of a major teaching hospital. Patients with a history of childhood sexual abuse showed a marked clustering of four major risk factors for repeat DSH (unemployment, past deliberate self-poisoning, self-injury and psychiatric illness) and were significantly more likely to repeat DSH within the 6-month follow-up period. PMID- 8216588 TI - The gentle sex? Assaults on women by women. PMID- 8216589 TI - Out-of-district attenders: the passing trade of an accident and emergency department. AB - The resources of accident and emergency (A&E) departments are often required to treat patients who are not within the catchment population of the local health authority. An assessment of workload caused by this particular group was carried out over a 2-month period at Northampton General Hospital which serves a population of 318,000. Details were collected and analysed on the patients' reason for attendance, investigations and treatment. PMID- 8216590 TI - Short-stay facilities in accident and emergency departments for children. AB - This paper assesses short stay ward facilities for children in the United Kingdom. The results of a postal questionnaire indicate that 50% of departments surveyed have a short-stay ward. Of these 25% admit small numbers of children. These are mainly children who have sustained trauma-related problems. The potential role of paediatric short-stay ward facilities is discussed. PMID- 8216591 TI - Paediatric accident & emergency short-stay ward: a 1-year audit. AB - A short-stay ward attached to the accident and emergency (A&E) department has opened recently. The development of this ward is described together with its operation over a 1-year period. Head injuries were the commonest reason for admission. Only 7% of children stayed longer than anticipated or were considered inappropriate admissions. PMID- 8216592 TI - The need for better pre-hospital analgesia. AB - Many patients arrive at the accident and emergency (A&E) department in pain. To quantify this problem a retrospective analysis was performed of the clinical records of 502 consecutive patients arriving by ambulance at the A&E department over a 20-day period. A total of 273 (54%) of the patients had pain as a symptom on arrival and 69 (14%) were given opioid analgesia in the A&E department. Sixty of those given opioids had a single limb fracture. A survey of all ambulance services in the U.K. was conducted by means of a postal questionnaire sent to chief ambulance officers. Only five out of 65 services give any analgesia other than Entonox (B.O.C.). There were wide variations in the attitudes of services around the country to future developments. The authors suggest that paramedics should be trained to administer intravenous opioid analgesia. PMID- 8216593 TI - The injured motor cycle messenger. AB - Injured motor cycle messengers make up a small but significant proportion of the young injured attending Central London accident and emergency (A&E) departments. The study confirms that the pattern of their injuries is similar to other injured urban motor cyclists, and discusses the background of the injured, in terms of experience and training, highlighting the frequency of injury and possible predisposing factors. A total of 116 injured motor cycle messengers attending two Central London A&E departments over a 10-month period were studied. Thirteen per cent sustained sufficiently serious injuries to necessitate admission, the rest were treated as out-patients for lesser injuries. The mean age was 23. Only 18% had received any formal training and 31% were in possession of a provisional driving license only. Fifty-eight per cent had been employed as a messenger for less than 3 months, yet two-thirds of them had sustained a previous injury whilst a messenger. The apparent absence of supervision of this potentially dangerous occupation is emphasized. In view of the repeated injuries sustained by many of these vulnerable young men, it is suggested that those responsible for their treatment might, in addition to their therapeutic role, give suitable guidance that might prevent re-attendance with further injuries. PMID- 8216594 TI - Evaluation of whiplash injuries by technetium 99m isotope scanning. AB - Despite the frequency with which whiplash injuries present to accident and emergency (A&E) departments, there lacks an objective investigation to define the severity of the initial injury or the morbidity that may ensue. Following reports on the effectiveness of isotope bone scanning for soft tissue and ligament injuries a study was undertaken of isotope scanning of whiplash injuries. The objectives of the study were to isolate the anatomic site of the injury and to quantify the severity of the injury with relation to the concentration of isotope uptake and subsequent morbidity. PMID- 8216595 TI - An audit of care received by patients injured during sporting activities. AB - A summary of injuries sustained by 340 sportsmen over 9 successive weekends from 16 November 1991 to 12 January 1992 attending an accident and emergency (A&E) department is presented. Most injuries occurred in young males usually as a result of soccer or rugby. Sixty-seven per cent of patients were discharged with no further followed up in hospital. Seventy-two per cent of patients were X rayed, 33% of X-rays showed a fracture or dislocation. A total of 193 attendees received minimal treatment, (defined as discharge with advice only, simple analgesia or strapping only with no hospital follow-up) and of these 152 were X rayed. A total of 100 patients who received minimal treatment were selected randomly by computer to receive a follow-up letter asking about certain issues relating to their care in the A&E department. Most patients felt that the A&E Department was the most appropriate source of treatment for their sports injury, and over half attended specifically for an X-ray examination. Despite the doctors view that many of these minor injuries could have been self-treated, few patients felt able to treat future similar minor injuries themselves. They were, however, more likely to go elsewhere for treatment on subsequent occasions. PMID- 8216596 TI - Atraumatic brachial plexopathy following intravenous heroin use. AB - A 32-year-old man presented to the accident & emergency (A&E) department complaining of an inability to use his left arm and shoulder. The previous day he had injected heroin intravenously into his left antecubital vein. Examination revealed signs of a left-sided brachial plexus lesion. There was no history or sign of trauma. Neurological investigation revealed motor and sensory loss compatible with a complete brachial plexus lesion. He exhibited a very rare condition, asymmetrical atraumatic brachial plexopathy, thought to result from an inflammatory cause, which not only affects the brachial, but also other plexi or individual nerves in the body and thought to be related to repeated intravenous use of heroin. This is a condition for which there is no specific treatment but which usually resolves spontaneously in the absence of continuing heroin misuse. PMID- 8216597 TI - The role of activity-related groups in assessing workload in the accident and emergency department. AB - Workload of the Accident & Emergency (A&E) Department at Barnet General Hospital was studied over a 1-year period. All new patients were divided into Activity Related Groups (ARGs). Doctor work hours, for the year, were calculated utilizing the ARGs. This provided an estimate of the minimum required staffing level. ARGs are a potentially useful tool in auditing workload of individual doctors and the department as a whole. PMID- 8216598 TI - Telephone advice in the accident and emergency department: a survey of current practice. AB - The objective of this study was to assess the standard of advice given by telephone by accident and emergency (A&E) departments following patients' enquiries. In order to do this patient enquiries were simulated and a telephone questionnaire was carried out. The study was carried out in 18 major and 16 minor A&E departments in Wales. Results achieved were that overall, correct telephone advice was given to 72 of 97 simulated patients (74%). Sixty calls were dealt with by the nursing staff (62%) who gave correct advice on 41 (68%) occasions. No A&E department had a formal policy nor provided staff training for handling patients' enquiries by telephone. It is concluded that A&E departments should train designated members of staff, preferably the triage nurse, who would formally deal with telephone enquiries requiring medical advice. There should be formal documentation of the enquiry and advice proffered as part of a departmental policy. PMID- 8216599 TI - Nurse triage in theory and in practice. AB - 'Nurse Triage' refers to the formal process of early assessment of patients attending an accident and emergency (A&E) department by a trained nurse, to ensure that they receive appropriate attention, in a suitable location, with the requisite degree of urgency. The benefits claimed for nurse triage include better patient outcomes, through clinical management reaching those in greatest need of it first. A recent study of nurse triage in a British A&E department failed to demonstrate the benefits claimed: patients undergoing triage were delayed, especially those in the most urgent groups. No differences were noted between the two study groups in levels of satisfaction with the A&E process. The results brought forth criticism from all quarters. In this paper the points made by the critics are considered, and an attempt to answer them is made. PMID- 8216600 TI - Intraperitoneal bladder rupture and the wearing of rear seat-belts--a case report. PMID- 8216601 TI - Aeromonas hydrophila infection of a scalp laceration (with synergistic gas gangrene). PMID- 8216602 TI - An important complication of upper cervical spine fracture: a case report. AB - A case report is presented of a patient who sustained a high cervical spine fracture, the possible mechanisms of injury and details of the fracture are discussed. The patient developed bilateral vagal nerve palsies 48 h after the accident. This complication was only recognized after dysphagia and an aspiration pneumonia developed. The complication of aspiration pneumonia was preventable. Meticulous and repeated examination of the cranial nerve function in this type of injury is recommended. Normal feeding should commence only when the cranial nerve function has been shown to be normal after repeated examination. PMID- 8216603 TI - Emergency treatment of adder bites: case reports and literature review. AB - Five cases of adder bites are presented. The clinical effects and current recommendations for the treatment of adder bites are described based on a review of previously published literature. All adder bites, or snake bites of unknown species, should be observed for a minimum of 2 h. Those with no local swelling may be allowed home with appropriate antitetanus prophylaxis. Patients with local reaction or signs of systemic envenoming should be admitted for 48 h with ECG monitoring, and antivenom obtained. Indications and precautions for administration of antivenom are reviewed. Early antivenom treatment may reduce mortality and morbidity from adder bites. PMID- 8216604 TI - The conservative treatment of mallet finger with a simple splint: a case report. AB - Sixty patients with mallet finger deformity were randomly treated with either a Stack or a custom-made padded aluminium alloy malleable finger splint. Both splints were equally effective in correcting the deformity but the aluminium alloy splint was able to be fitted to a wider variety of finger shapes and sizes and caused significantly fewer skin complications. PMID- 8216605 TI - Methaemoglobinaemia as a result of sodium nitrate poisoning. PMID- 8216606 TI - Forced hyperextension to the wrist. PMID- 8216607 TI - X-rays as a diagnostic aid in winged scapula. PMID- 8216608 TI - Bilateral pneumothoraces. PMID- 8216609 TI - Interaction and compartmentalization of the components of bacterial enzyme systems involved in cell energetics. AB - Bacterial enzyme systems, especially those which are involved in cell energetics, often show a common characteristic feature: their constituents (either interacting enzymes or subunits of a given enzyme complex) are physically separated. They are located in different functional entities, such as cytoplasm or periplasmic space. This kind of cellular and macromolecular organization enables the cell to establish spatially separated but neighbouring zones in which distinct conditions are created or maintained. This intrinsic imbalance is one of the keys for the process of life. As the mediator between the two compartments, the cytoplasm and the periplasmic space, the cytoplasmic membrane--itself a functional entity--not only acts as a barrier, but carries a set of functional enzyme components, thus contributing to the interaction between compartments. Examples to illustrate this concept are enzyme systems involved in anaerobic glycine metabolism, aerobic utilization of carbon monoxide, proton or sodium translocation across the membrane, and intracellular hydrogen cycling used by the cell for the generation of a proton gradient. PMID- 8216610 TI - Antioxidative properties of phenazone derivatives: differentiation between phenylbutazon and mofebutazon. AB - Both phenylbutazon and mofebutazon inhibit oxidative fragmentation of the methionine derivative, 2-keto-4-methylthio-butyric acid (KMB) by xanthine oxidase -or diaphorase mediated OH radical production. Differentiation of the two non steroidal antiinflammatory drugs is possible by means of determining oxygen reduction by xanthine oxidase or diaphorase in the presence of the naphthoquinone, juglone, where only mofebutazon shows an inhibitory effect. PMID- 8216611 TI - Phellodonic acid, a new biologically active hirsutane derivative from Phellodon melaleucus (Thelephoraceae, Basidiomycetes). AB - A new hirsutane derivative, phellodonic acid (1), has been isolated from fermentations of Phellodon melaleucus strain 87113. Its structure was elucidated by spectroscopic methods. The compound exhibits antibiotic activities towards bacteria and fungi. 1 is the first bioactive metabolite from cultures of a species belonging to the family Thelephoraceae. PMID- 8216612 TI - A protein cross-reacting with anti-spectrin antibodies is present in higher plant cells. AB - Proteins that react with anti-human spectrin antibodies raised in rabbit were found in pea seedlings and leaves. The immunoreactive proteins seem to be associated with the membranes and can be extracted with low ionic strength solutions. PMID- 8216613 TI - Survey of the taxonomic and tissue distribution of microsomal binding sites for the non-host selective fungal phytotoxin, fusicoccin. AB - The recent identification of the fusicoccin-binding protein (FCBP) in plasma membranes from monocotyledonous and dicotyledonous angiosperms has opened the basis for an elucidation of the toxin's mechanism(s) of action and indicated a widespread occurrence of the FCBP in plants. Results of a detailed taxonomic survey of fusicoccin-binding sites are reported. Binding sites were not found in prokaryotes, animal tissues, fungi and algae including the most direct extant ancestors of the land plants (Coleochaete). From the Psilotales (Psilophytatae) to the monocotyledonous angiosperms, all taxa analyzed possessed high-affinity microsomal fusicoccin-binding sites. A heterogeneous picture emerged for the Bryophyta. Anthoceros crispulus (Anthocerotae), the only hornwort available to study, lacked fusicoccin binding. Within the Hepaticae as well as the Musci, species lacking and species exhibiting toxin binding were found. The binding site thus seems to have emerged very early in the evolution of the land plants. The tissue distribution of fusicoccin-binding sites was studied in Vicia faba L. shoots. All tissues analyzed showed fusicoccin binding, although not to the same extent. On a per-cell basis, guard cells were found to contain, compared to mesophyll cells, a nine-fold higher number of binding sites. Based on cell surface area, the site density is by a factor of 32 higher in guard cells than in mesophyll cells. Tissue specific expression of the binding sites is suggested by these findings. PMID- 8216614 TI - X-ray studies on phospholipid bilayers. XIII. Interactions with gentamicin. AB - This study deals with the structural perturbations that the aminoglycoside antibiotic gentamicin (GENT) can produce to phospholipid bilayers. Two multi bilayer systems, one built-up of dimyristoylphosphatidylcholine (DMPC) and the other of dimyristoylphosphatidylethanolamine (DMPE) were allowed to interact with GENT. The experiments were performed in both a hydrophobic and a hydrophilic medium below the phospholipid main transition temperatures. X-ray diffraction techniques were used to determine the extent of the perturbation induced by GENT. The maximum effect was attained when GENT interacted with DMPC in the hydrophobic medium. On the other hand, GENT in aqueous solutions was unable to perturb in any significant extent the structure of the phospholipids under study. PMID- 8216615 TI - Identification and cytogenetic analysis of an abnormal pig chromosome for flow cytometry and sorting. AB - For cytogenetics of pig (Sus scrofa domestica) and the influence of chromosome aberrations on pig production, high interest exists in flow sorted chromosomes for gene mapping, to establish DNA-libraries, or to produce DNA-probes. Flow karyotyping and sorting as well as slit scan flow analysis of metaphase chromosomes of an abnormal cell type carrying a translocation marker chromosome 6/15 are described. Flow sorting of the largest chromosomes of these cells was performed. After sorting the chromosomes still had a well preserved morphology and were identified microscopically by G-banding. The quality of the band pattern of the sorted chromosomes was compatible to that of isolated chromosomes not subjected to flow cytometry. The sorted fraction showed an enrichment of chromosome 6/15 and chromosome 1 which have quantitatively about the same integrated fluorescence intensity. Slit scan flow analysis was performed to discriminate these two chromosomes. Metacentric and submetacentric chromosomes were analyzed according to their bimodal slit scan profiles. Profiles of the largest chromosomes were distinguished by their different centromeric indices. Two groups were interpreted as the normal chromosome 1 and the translocation chromosome 6/15. PMID- 8216616 TI - The relationship of spoken-English proficiencies of foreign medical school graduates to their clinical competence. PMID- 8216617 TI - A retrospective analysis of a program designed to facilitate the entry of underrepresented-minority students into medical school: program trends and outcomes. PMID- 8216618 TI - Randomized controlled trial of a combined video-workbook educational program for CME. PMID- 8216619 TI - Recognition of computer-based materials in the promotion guidelines of U.S. medical schools. PMID- 8216620 TI - A preliminary study of the validity of scores and pass/fail standards for USMLE steps 1 and 2. PMID- 8216621 TI - Relationships of ratings of clinical competence and ABIM scores to certification status. PMID- 8216622 TI - Performances of men and women on NBME Part I and Part II: the more things change.... PMID- 8216623 TI - Student perceptions of the effectiveness of a problem-based surgery curriculum. PMID- 8216624 TI - Topics for discussion reported by students using clinical cases in problem-based tutorials during a basic science course. PMID- 8216625 TI - Internal medicine ambulatory-care-based education: a comparison of three models. PMID- 8216626 TI - A longitudinal ambulatory care clerkship: graduates' reports on the effect on specialty choice and preparation for residency. PMID- 8216627 TI - An objective structured clinical examination for the licentiate of the Medical Council of Canada: from research to reality. PMID- 8216628 TI - Reactions of psychiatric inpatients to medical student interviews. PMID- 8216629 TI - The impact of medical education on students' perceptions of patients. PMID- 8216630 TI - Stress among residents, medical students, and graduate science (MSc/PhD) students. PMID- 8216631 TI - What do medical students mean when they say "sexual harassment"? PMID- 8216632 TI - Changing interest in family medicine and students' academic performance. PMID- 8216633 TI - Specialty choice during the clinical years: a prospective study. PMID- 8216634 TI - Diagnostic accuracy as a function of case prototypicality. PMID- 8216635 TI - The influence of vignettes on EKG interpretation by third-year students. PMID- 8216636 TI - Using clinician ratings to model score weights for a computer-based clinical simulation examination. PMID- 8216637 TI - Practice in medically underserved areas: medical students' attitudes and intents. PMID- 8216638 TI - A comparison of pass/fail classifications made with scores from the NBME standardized-patient examination and Part II examination. PMID- 8216639 TI - First-year medical students' attitudes toward access to medical care and cost containment. PMID- 8216640 TI - Impact of repeated use of objective structured clinical examination stations. PMID- 8216641 TI - The effect of deliberate, excessive violations of test security on performance on a standardized-patient examination. PMID- 8216642 TI - Problem-based learning: have the expectations been met? PMID- 8216643 TI - Issues in medical education: basic problems and potential solutions. PMID- 8216644 TI - Evaluating faculty clinical excellence in the academic health sciences center. AB - Although excellence in the clinical care of patients is the cornerstone of medicine, academic health sciences centers have increasingly given more weight to research and correspondingly less emphasis to patient care. To better recognize and reward clinical excellence, it is first necessary to effectively evaluate physicians' performances in patient care. In addition to addressing the value of faculty clinical excellence in the academic setting, the authors discuss different approaches to clinical assessment, theoretical and practical problems in assessing the performances of clinical faculty, and a system of evaluation being initiated at the University of Virginia School of Medicine. This system of evaluation combines--in annual individual reviews--a limited amount of objective assessment data with subjective evaluations from several sources. The objective data include board certification and recertification, analysis of outcomes data, and documentation of scholarly activity. The subjective evaluations include letters of recognition and appreciation from faculty colleagues and written observations from department chairs, housestaff, students, and nurses. The system has been accepted by department chairs, members of the Promotion and Tenure Committee, and the general faculty. In implementing this new system, periodic review of the pace and direction of change will be crucial to track progress and provide feedback for further modification. PMID- 8216645 TI - Introduction of total quality management (TQM) into an internal medicine residency. AB - In spite of significant enthusiasm for the principles and methods of total quality management (TQM) in health care organizations, there have been only a few creative programs applying TQM to medical education. In addition, teaching programs are under significant pressure to teach and practice cost-effective medicine and to produce more sophisticated general internists. In July 1992, the governance and operation of the internal medicine training program at Cedars Sinai Medical Center was restructured to integrate a TQM program with a health services research section and a resource management department. This restructured program transfers significant programmatic responsibility and power to houseofficers. Within the playing field defined through a housestaff values statement and requirements of the Accreditation Council for Graduate Medical Education and the American Board of Internal Medicine, the housestaff have brought about substantial change. The first housestaff survey after the new program was operational for six months revealed that 68% of the 77 respondents felt the housestaff had greater programmatic influence, 68% felt that the rate of program change was "better," and 63% felt the overall training program had improved, while 3% felt it had worsened after the restructuring. Fifty-six percent of the housestaff felt the new program should be continued unchanged, and 29% felt it should be continued with changes. Housestaff teams have approached educational issues, quality-of-care problems, and resource management challenges through formal scientific problem-solving techniques. This article discusses the lessons learned in the first six months and the program improvements that will be attempted in the future.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216646 TI - "Invisible" doctors: making a case for involving medical residents in hospital quality improvement programs. AB - The author maintains that residents should be as actively engaged in the evaluation and improvement of the inpatient and ambulatory care they deliver as staff physicians are, and that to exclude them from their departments' formal quality assessment and assurance program wastes valuable opportunities to train them and to improve patient care. For example, residents can benefit from process of-care reviews, which help teach them the standards of adequate medical care and motivate them to improve the care they give. Residents can also benefit from participating in the quality assessment process itself; this will help develop their clinical and analytic skills, hone their skills in searching and critiquing the medical literature, and help them understand the links between the processes and outcomes of care. In addition, systematic, criteria-based reviews of residents' clinical competence in the diagnosis and treatment of common medical conditions can help attending physicians and residency directors evaluate the residents' abilities. And finally, hospitals benefit from the involvement of housestaff in the quality improvement program, since housestaff often have more insight than staff physicians or administrators into aspects of the physical plant or organizational structure that impair clinicians' ability to provide good care. The author gives examples for each of the preceding statements, and concludes by saying that when residents are treated as if they are "invisible" in quality assessment programs, the program staff is in some measure abdicating its responsibility for the residents' education and for the well-being of the program's current and the residents' future patients. PMID- 8216647 TI - Developing therapeutic relationships in multicultural settings. AB - The expertise of native peoples as well as resources drawn from humanities, education, and arts organizations in Arizona contributed to an educational program to heighten the cultural sensitivity of health care professionals at the Children's Health Center of St. Joseph's Hospital. The sentiment expressed by Kraut that "respect for the cultural preferences and taboos of more traditional medical systems thus renders American physicians more effective and in the long run more efficient" is supported by our experience with this program. PMID- 8216648 TI - Community partnerships: toward a new South African health care system. PMID- 8216649 TI - The role of the NIH in a national prevention strategy. PMID- 8216650 TI - Expanding medicine's knowledge base. PMID- 8216651 TI - Requirements for speakers at "promotional" educational activities versus independent CME activities. PMID- 8216652 TI - Multi-university residency training. PMID- 8216653 TI - Effects of family dysfunction on medical students. PMID- 8216654 TI - Brief group consultations for residents. PMID- 8216655 TI - Mock ethics trial for medical students and law students. PMID- 8216656 TI - A randomized, controlled pilot study of placing third-year medical clerks in a continuity clinic. AB - BACKGROUND: Because of the great interest in developing ambulatory care components within medical school curricula, there is a need for outcome data concerning such changes. METHOD: In 1991-92, 40 third-year students at the University of California, San Francisco, School of Medicine were assigned to the San Francisco Veterans Affairs Medical Center for their core medicine clerkships; ten of these students were exposed to ambulatory care by being assigned to medical residents who worked in a general medicine continuity clinic. The ten students in the continuity clinic and the 30 who were not were evaluated by means of their (1) final clerkship evaluation scores for overall competence, (2) performances on a standardized-patient exercise where the majority of the simulations were of ambulatory care problems, and (3) self-assessment of clinical skills and knowledge and attitudes about primary care. Student's t-test was used to determine whether there were statistically significant differences between the performances of the two groups. In addition, the students in the clinic kept diaries about their clinic experiences. RESULTS: No significant difference was found between the two groups of students on the objective or subjective measures of evaluation, although the diary narratives of the clinic students revealed that they were extremely enthusiastic about the clinic experience. CONCLUSION: Because there was no significant difference between the performances of the two student groups, the ambulatory care model in this study, despite its feasibility to implement, was not adequate to teach the students the different problem-solving and therapeutic skills necessary in the ambulatory care setting. PMID- 8216657 TI - The influence of philosophical versus theological education on the moral development of clinical medical ethicists. AB - PURPOSE: Because of the increasing involvement of clinical medical ethicists in patient care and the resultant controversy over the appropriate background, training, and certification of clinical ethicists, this study was designed to investigate whether different educational backgrounds (philosophical versus theological) affected the moral reasoning of clinical ethicists and their orientations toward justice or care. METHOD: From 1987 through 1990, extensive oral interviews were conducted with 50 clinical medical ethicists (26 philosophers and 24 theologians) who were at 32 medical centers in 14 states from all sections of the United States. The interviews were used to gather selected demographic characteristics about the ethicists (age, gender, and educational background) as well as to determine the ethicists' scores for stages of moral reasoning and for moral orientation. Polyserial correlations and multivariant analyses were then performed between the demographic characteristics and the data on moral reasoning and moral orientation. RESULTS: The philosophers and theologians were found not to be significantly different (p > .05) in their moral reasoning skills in terms of either moral stage score or weighted average score. Similarly, the philosophers and theologians were found not to be significantly different in their moral orientations toward justice or care in terms of recognition, predominance, or alignment. No significant relationship was found between age or gender and moral reasoning or moral orientation. CONCLUSION: Based on the results of this study, it appears that clinical medical ethicists, whether philosophers or theologians, are a fairly homogeneous group with regard to their moral development, in terms of both their stages of moral reasoning and their moral orientations toward justice and care. PMID- 8216658 TI - A comparison of the moral reasoning of physicians and clinical medical ethicists. AB - BACKGROUND: Because of the increasing controversy over who should provide ethics consultations, this study investigated differences in the moral reasoning and moral orientations of physicians and clinical ethicists. METHOD: From 1987 through 1990, extensive interviews were conducted with 39 physicians and 50 clinical medical ethicists (26 philosophers and 24 theologians) who were at 32 medical centers in 14 states from all sections of the United States. The interviews were used to gather selected demographic characteristics (age, gender, and profession--physician or ethicist) for the 89 individuals as well as to determine their scores for moral reasoning and moral orientation. Polyserial correlations and multivariant analyses were then performed between the demographic characteristics and the data on moral reasoning and moral orientation. RESULTS: The physicians consistently scored lower than the clinical ethicists in their moral reasoning skills in terms of both moral stage score (p < .01) and weighted average score (p < .01). However, the physicians were found not to be significantly different (p < .05) from the clinical ethicists in their moral orientations toward justice or care in terms of recognition, predominance, or alignment. No significant relationship was found between age and moral orientation. A significant relationship was found between age and stage of moral reasoning, with the older individuals scoring higher. No significant relationship was found between gender and stage of moral reasoning. A significant relationship was found between gender and moral orientation: the women were more likely to recognize elements of care in moral dilemmas and the men more likely to recognize elements of justice. CONCLUSION: This study provides initial evidence that clinical medical ethicists, whether philosophers or theologians, may be better skilled than physicians to do ethicists consultations. To the extent that higher levels of moral reasoning correlate with superior skills in performing clinical ethics consultations, this study shows the value of bringing philosophers and theologians into the clinical setting. PMID- 8216659 TI - Predicting the first-year performances of international medical graduates in an internal medicine residency. AB - BACKGROUND: Recent growth in the number of international medical graduates (IMGs) -i.e., graduates of non-U.S. and non-Canadian medical schools--who fill positions in internal medicine residencies requires examination of the predictive validity of selection criteria. METHOD: Data were analyzed for 46 foreign-born IMGs who entered the internal medicine residency at Wright State University School of Medicine between January 1985 and January 1991. The t-test and Pearson correlation were used to relate ten selection variables (age, gender, foreign clinical experience, U.S. clinical experience, clinical experience in the two years prior to residency, time between medical school graduation and residency, performance on the Foreign Medical Graduate Examination in the Medical Sciences- FMGEMS--Parts I and II, interview language skill, and interview rank category) to performance ratings the IMGs received in the first year of residency. RESULTS: Only performance on the FMGEMS Part I (p = .045) and clinical experience in the two years prior to residency (p = .005) were related significantly to subsequent performance in residency. CONCLUSION: The results suggest that recent clinical experience and performance on standardized examinations are the two selection criteria most predictive of foreign-born IMGs' first-year performances as internal medicine residents. PMID- 8216660 TI - Comparison of housestaff's estimates of their workday activities with results of a random work-sampling study. AB - BACKGROUND: Accurately quantifying housestaff's workday activities is acquiring increasing importance as resources become constrained and programs become more accountable for medical education. The authors compared a traditional method of time analysis based on housestaff's estimates of how they spent their workdays with the results of a formal time-analysis study based on random work sampling. METHOD: All housestaff (18 interns and 18 residents) rotating on a general medicine service at Duke University Medical Center between December 1991 and March 1992 participated in the study. Twenty-six of the housestaff first provided estimates of how they spent their workdays, and then all 36 wore random reminder beepers and recorded what they were doing (activity) and with whom (contact) at each beep. RESULTS: The housestaff overestimated the amounts of time spent in patient evaluation (e.g., the mean estimated proportion of time spent performing histories and physical examinations was 29%, whereas the mean actual proportion was 17%) and in educational activities (e.g., the mean estimated proportion of reading time was 8.4%, whereas the mean actual proportion was 2.7%). The housestaff underestimated the amount of supervision by attending physicians: the mean estimated proportion was 7.7%, whereas the mean actual proportion was 16.9%. CONCLUSION: The Housestaff's estimates of workday times differed from the observed times measured by random work sampling. These inaccuracies were manifest in several important areas, such as patient evaluation, educational activities, and attending physicians' supervision. These results suggest that program directors who seek to describe housestaff's work activities or wish to determine the effects of administrative interventions should use random work sampling as the measure. PMID- 8216661 TI - Comparing different types of performance feedback and computer-based instruction in teaching medical students how to diagnose acute abdominal pain. AB - PURPOSE: To examine the relative efficacies of three types of performance feedback used with computer-based instruction (CBI) in making diagnoses. METHOD: In 1990, 75 final-year medical students at The University of Queensland were pretested for domain knowledge and diagnostic skill in the area of acute abdominal pain. The students were also asked to indicate their confidence in each of their diagnoses. Following these pretests, the students were randomly divided into five groups of 15 students each. One group received traditional CBI, using a "question-and-explanation" format, to learn domain knowledge. The other four groups received one of two types of CBI to learn diagnostic accuracy, and these four groups received one of three types of performance feedback (which differed considerably in the amounts of information imparted). Then the students took posttests. One-way analysis of variance, Student's t-test, and the Tukey test were used to compare the performances of the different groups of students. RESULTS: Although the students in the traditional CBI group significantly improved their performance on multiple-choice questions (by 58%) compared with the other groups of students (6-10% improvement), these students did not improve their diagnostic performance. In contrast, the CBI groups that used simulated patient cases and structured-performance feedback did improve their diagnostic accuracy (by as much as 16%, compared with a 1% decline for the traditional CBI group). Contrary to expectation, the different types of feedback were equally effective. Except for the students in the traditional CBI group, the students' confidence increased from pretest to posttest regardless of their performances. CONCLUSION: CBI that uses simulated-patient cases and structured-performance feedback seems to be efficient and effective compared with traditional CBI methods. However, care should be taken to ensure that students do not become overconfident of their abilities. PMID- 8216662 TI - Specialty preferences of 1993 medical school graduates. PMID- 8216663 TI - [The characteristics of colloid osmotic pressure and hematocrit following human albumin substitution as an indication of permeability disorders in septic complications]. AB - Out of a pool of the postoperative intensive care patients in Anaesthesiological and Intensive Care Clinic, Berlin-Friedrichshain, 26 patients with hypoalbuminaemia after major abdominal surgery were selected. Septic complications occurred in 13 patients. In a comparative study we analysed colloid osmotic pressure and haematocrit after substitution of human serum albumin. In cases of septic complications, human serum albumin substitution did not lead to an increase of colloid osmotic pressure and in all cases the haematocrit persisted at the initial value or rose. It is discussed that both parameters can be early references to permeability disturbances. Uncritical use of human serum albumin in septic patients can be the cause of disturbances of organ functions, especially of the lungs. An alternative for improving the oncotic situation is the use of high molecular weight hydroxy-ethyl-starch (molecular weight 200,000). PMID- 8216664 TI - [Intra- and postpartum cortisol concentrations during fentanyl anesthesia]. AB - In a clinical study the course of cortisol concentration in serum was investigated at the following points: under labour, directly post partum simultaneously in the mother, the umbilical artery and vein and on the first and second day after birth in the mother and on the second third days in the newborn. Two groups of patients were investigated: 51 first and multiple parturients with peridural fentanyl analgesia for labour pain relief (PFA) and 42 first and multiple parturients as control group. The reduction of stress under PFA could be confirmed by measurement of cortisol concentrations in serum. The cortisol concentrations listed according to the time of day showed significantly lower values for the multiple parturients compared with the control group. Circadian peaks of the intrapartal cortisol in serum are generally absent in the multiple parturients. In the first parturients of the PFA group a more differentiated course of the cortisol levels listed according to the time of the day was observed. Up to about noon, the cortisol values are markedly lower than those of the control group, but after decreasing tendency in the early afternoon, they show another peak around 4.00 p.m. This means there is still a circadian rhythm under the influence of PFA for the first parturients. In contrast to the multiple parturients, the reaction of the cortisol level of the first parturients after PFA is only of short duration. At the other measuring points there are possibly different stress factors such as permanent expectation under labour and the absence of labour experience, superposing the fentanyl effect seen in the cortisol levels of the multiple parturients. PMID- 8216665 TI - Painless dental extraction in children. AB - A controlled investigation was undertaken to compare topical lignocaine and rectal paracetamol in the prevention of pain after day case dental extraction in children under general anaesthesia. Sixty patients were allocated randomly to receive intraoperatively either topical lignocaine 4 mg/kg (group A), rectal paracetamol 10 mg/kg (group B) or no analgesia (group C) immediately after completion of surgery. Pain, appearance and side-effects were assessed 15, 30 and 60 minutes postoperatively. The patients who received topical lignocaine (group A) had significantly lower pain scores at 15 minutes (p < 0.001) and 30 minutes (p < 0.01) with no need for postoperative analgesia. The use of topical lignocaine was associated with a significantly (p < 0.01) more rapid return to a calm awake appearance at 15 and 30 minutes postoperatively. Patients in group C who received no analgesia at the end of the operation received 10 mg/kg acetyl salicylic acid intramuscularly after their return to the ward. No significant differences in the incidence of nausea, vomiting, or any other toxic reaction were found between the three groups. The improved analgesia and shorter recovery period topical lignocaine render it more satisfactory for the prevention of pain after day dental extraction in children than the more commonly used rectal paracetamol. PMID- 8216666 TI - [Procedure following an unforeseen incident: what can one, should one, must one do from the legal point of view?]. AB - The danger that an anaesthesiologist becomes involved in a malpractice lawsuit has greatly increased over the last few years. It is therefore of considerable importance that anaesthesiologists know how they should conduct themselves from a legal point of view, when such a situation arises. Ten recommendations are summarized. PMID- 8216667 TI - Thiolupinine and some derivatives of pharmacological interest. AB - The (quinolizidin-1 alpha-yl)methanthiol (thiolupinine) was prepared and, utilizing the thiol group reactivity, several S-substituted derivatives were obtained among which was a group of 3-[(lupinylthio)methyl]indoles. Eight of the prepared compounds were subjected to a broad pharmacological screening that evidentiated for many of them good level of the following activities in vivo and in vitro: antiarrhythmic, local anesthetic, negative chronotropic on isolated atria, calcium antagonism on ileum and atria, inhibition of spontaneous contraction of isolated trachea, inhibition of guinea pig ileum contractions induced by angiotensin I and II, bradykinin and cholecystokinin, inhibition of platelet aggregation induced by PAF and ADP. Single compounds were remarkable for additional antagonistic activities: 4 against P1-purine receptor, 8 against substance P, 12 against methacholine and 13 strongly inhibited arachidonate induced platelet aggregation. Very peculiar was the ability of compound 6 to protect mice from PAF induced mortality. PMID- 8216668 TI - Tricyclic heteroaromatic systems pyrazolo[1,5-a]quinoxalines: synthesis and benzodiazepine receptor activity. AB - The synthesis and the benzodiazepine receptor activity of some pyrazolo[1,5 a]quinoxalines bearing various substituents on the tricyclic heteroaromatic system are reported. Only one of the tested compounds showed some receptor affinity. PMID- 8216669 TI - Tricyclic heteroaromatic systems 1,2,4-triazolo[1,5-a]quinoxalines: synthesis and benzodiazepine receptor activity. AB - The synthesis, the benzodiazepine binding activity and the "in vitro" biological effect of some 1,2,4-triazolo[1,5-a]quinoxalines, 3-aza-analogues of some previously reported pyrazolo[1,5-a]quinoxalines, are described. Molecular modelling is used to define the structural requirements of the benzodiazepine recognition site which influence the affinity and different efficacy of these rigid ligands. PMID- 8216670 TI - N-arylpiperazinyl derivatives of 2,3-dihydrobenzoxazin[1,4]-3-ones synthesis and normolipemic activity. AB - Four series of N-arylpiperazinyl derivatives of the 7-substituted 2,3 dihydrobenzoxazin[1,4]-3-one were synthesized and preliminarily tested for hypolipemic activity. Substitutions in position 2 were performed. Hypotriglyceridemic activity was shown to be present in a number of compounds. PMID- 8216671 TI - Synthesis, antifungal, antibacterial and antiviral effects of some adamantaneketoxime ethers. AB - A number of adamantaneketoxime ethers and an acetylenic adamantaneketoxime iododerivative have been prepared and tested as potential antifungal agents. They were also examined for their antibacterial and antiviral effects. Most of them proved active against the tested fungi. Their antimicrobial activity was generally low, while they did not exhibit a "specific" antiviral activity against any of the viruses tested. PMID- 8216672 TI - Antifungal agents. VI. In vitro antifungal activities of halobenzoyl esters of cis- and trans-[2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3- dioxolan-4 yl]carbinols. AB - The synthesis and the in vitro antifungal activities against Candida albicans and Candida spp of a number of halobenzoyl esters of cis- and trans- [2-(1,1' biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan -4- yl]carbinols is reported. Some new imidazoles were found more active than ketoconazole and sometimes as potent as bifonazole against Candida albicans. All derivatives were found scarcely active against Candida spp. PMID- 8216673 TI - Synthesis and evaluation of the antiviral activity of acyclic nucleosides carrying fluorine and sulfur substituents. AB - -2',3'-Seco nucleosides 5 carrying fluorine and sulfur substituents at C-3' and C 5', respectively, of acyclic sugar moiety were synthesized in enantiomerically and diastereoisomerically pure form. These products and some structurally similar 1',2'-seco-2'-nor-and 1',2'-seco-nucleosides 3 and 4 were tested in vitro for cytotoxicity and antiviral activity. At non-cytotoxic concentrations the compounds were inactive against human immunodeficiency virus and herpes simplex virus type-1. PMID- 8216675 TI - Coulometric determination of some antiinflammatory compounds. AB - A method is presented for the chlorocoulometric assay of small amounts of piroxicam and tenoxicam. This assay is carried out directly by coulometrically titrating the investigated substances with electrogenerated chloride in the presence of methyl orange as indicator. Results are accurate and reproducible. The method can be applied for routine analysis of these substances. PMID- 8216674 TI - 2H-1-benzopyran derivatives with platelet antiaggregating and other activities. AB - The synthesis of some N,N-disubstituted 4-amino-5,6,7,8-tetrahydro-3,6- diphenyl 2H-1-benzopyran-2-ones by reaction of phenylchloroketene with a series of N,N disubstituted 2-aminomethylene-4-phenylcyclohexanones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid and an appreciable antiarrhythmic activity, as well as weak anti-inflammatory and local anesthetic activities in rats and mice. PMID- 8216676 TI - Synthesis and anticholinergic activity of some new N,N-disubstituted carbamodithioic acid 2-oxo-2-(diphenylamino) ethyl esters. AB - The synthesis of new N,N-disubstituted carbamodithioic acid 2-oxo-2 (diphenylamino) ethyl esters is reported. The structures of these compounds are supported by their UV, IR and 1H-NMR spectra, as well as by elemental analysis. The new compounds were tested for their anticholinergic activities. PMID- 8216677 TI - 1,2,3-Triazole[4,5-d]pyridazines--I. Analogues of prostaglandin synthesis inhibitors. AB - This paper reports the preparation of new triazolepyridazine derivatives bearing in the 1 position an acidic substituent, on the basis of a working hypothesis relating these compounds to 1,2,3-triazole derivatives, effective in vitro inhibitors of the prostaglandin synthesis. The tested compounds were lacking of biological activity. PMID- 8216678 TI - Synthesis of some 4-oxo-delta 2-thiazolin-2-ylhydrazones as potential antiprotozoal agents. AB - Several 4-oxo-delta 2-thiazolin-2-ylhydrazone derivatives 6 (6-1 - 6-19) derived from the cyclization reaction between the thiosemicarbazones 5 and homologous alpha-chloroacids were prepared. Only compound 6-2 was found to be active against Entamoeba histolytica and Trichomonas vaginalis. PMID- 8216679 TI - Writing for publication: it's easier than you think! PMID- 8216680 TI - Legislative news: DMERC surgical dressing update. PMID- 8216681 TI - Methicillin-resistant Staphylococcus aureus (MRSA) and wounds. PMID- 8216682 TI - Debridement: removal of non-viable tissue. PMID- 8216683 TI - Product notebook: a catheter anchoring device. AB - A prospective multi-center study was conducted to assess the use of a catheter anchoring device. Fifty-nine patients with catheters ranging in size from 8 to 30 French used 164 devices. The device was easy to apply and remove, facilitated catheter repositioning, prevented tension at the insertion site, and did not cause skin problems in the majority of patients. Compared to previous methods used, the mean wear-time for all catheters increased by 2 days when the anchoring device was used. When wear-time was correlated to catheter diameter, type, and location it was seen that patients with non-urinary catheters of less than 20 Fr diameters benefitted most from this device. Patients with foley catheters had the shortest wear-times. PMID- 8216684 TI - Product notebook: a conservative treatment for pressure ulcers. PMID- 8216685 TI - Proposed DMERC policies: a major threat to quality of care. PMID- 8216686 TI - Molecular analysis of the T-cell receptor V beta 5 and V beta 8 repertoire in pancreatic lesions of autoimmune diabetic NOD mice. AB - The repertoire of V beta 5 and V beta 8 T-cell receptors in pancreatic lesions of autoimmune diabetic NOD mice was analysed by sequencing the CDR3 and adjacent regions. T-cell receptor mRNA isolated from four different cell populations (i.e. spleen, lymph node, infiltrated islets from male and female NOD mice) was amplified by PCR and cloned; out of these, 339 clones were sequenced. Of 170 beta chains sequenced from intra-islet T cells, nearly 90% were unique and six other sequences were found 2 to 4 times. These data argue against any oligoclonality of the islet infiltrate. Despite the lack of clonal restriction, we observed a bias in TcR usage which indicates the existence of some selective pressure with regard to TcR structure. Of the V beta 5 positive cells, 30% to 40% showed a rearrangement of V beta 5 to J beta 2.6 and a complete lack of V beta 5-J beta 1.6 combination. The selective J beta usage was not restricted to islets but was found in all tissues analysed. V beta 8 positive cells did not show such an overrepresentation of V beta-J beta combinations with the exception of clones of infiltrated islets of partially diabetes-resistant male NOD mice. There the rearrangement of V beta 8-J beta 1.1 was markedly over-expressed. Analysis of the CDR3 region did not show selection of specific TcR with regard to region length. However, we found a restricted use of amino acids in the second position of the CDR3 region. V beta 8 chains had conserved an aspartic acid from the germline configuration in about half of the cases in all tissues analysed. V beta 5 chains also showed diversity of position 2 but not islet specificity of rearrangements. Mutated chains had a clear bias towards proline indicating selective pressure in favour of this amino acid. In conclusion, sequence analysis of V beta 5 and V beta 8 TcRs excludes oligoclonality of T-cell receptors in pancreatic lesions. The bias found for J beta usage and CDR3 structure was seen also in extra pancreatic tissues and thus probably is due to selective pressure during T-cell maturation in thymus or periphery. PMID- 8216687 TI - Antibody feedback regulation in MRL/lpr mice. AB - MRL/Mp-lpr/lpr (MRL/l) mice spontaneously develop autoimmune disease, characterized by glomerulonephritis, polyarteritis and polyarthritis. The lpr mice have defects in the Fas antigen, which plays a role in apoptosis, and it has been suggested that lack of negative selection of autoreactive T cells explains the initiation of the disease. The extremely high amount of autoantibodies may reflect additional immunoregulatory abnormalities. Antibody feedback regulation is an efficient way of up- or downregulating antibody responses. We have for the first time determined whether IgG-mediated suppression as well as IgM-mediated enhancement operates normally in these mice. MRL/l and MRL/Mp(-)+/+ (MRL/n) mice of different ages were therefore immunized with sheep erythrocyte (SRBC)-specific IgG or IgM antibodies followed by SRBC. Control groups received antigen alone. Five days later, the antigen-specific plaque-forming cell response was measured. IgG induced more than 90% suppression in both MRL/l and MRL/n in mice of all ages tested. This degree of suppression is in the same range as for other, normal mouse strains. In contrast, IgM-mediated enhancement was completely absent in 12 week-old MRL/l mice but normal in 8-week-old MRL/l as well as in MRL/n mice of all ages tested. When spleens and lymph nodes were immunohistochemically studied using a mAb specific for complement receptors 1 and 2 (CR1/CR2), an abnormal follicular structure was demonstrated in 12-week-old MRL/l mice. The antibody response of both 8- and 13-week-old MRL/l mice in vivo, after downregulation of these receptors, was inhibited by 85-96%. Thus, the presented data demonstrate that MRL/l mice with overt autoimmune disease are refractory to IgM-mediated enhancement of antigen-specific antibody production. We believe that this abnormal antibody feedback regulation is due to abnormal follicular structure in lymphoid organs of old MRL/l mice, hence the inability to localize and present antigen in a normal way. PMID- 8216688 TI - Comparative metabolism and structure of BCKD-E2 in primary biliary cirrhosis. AB - The identification and cloning of the mitochondrial autoantigens in primary biliary cirrhosis (PBC) have provided new clues in disease pathogenesis. The two major autoantigens are the E2 subunits of pyruvate dehydrogenase and branched chain ketoacid dehydrogenase (BCKD). Interestingly, one of these complexes, BCKD E2, is already well known to clinical medicine based on its association with genetic mutations in maple syrup urine disease (MSUD). Patients with this disease have an inability to metabolize branched-chain amino acids. In the present study, we have taken advantage of the known sequence of BCKD-E2 from normal humans, and addressed the issue of whether there is an altered autoantigen sequence in hepatocytes of individuals with primary biliary cirrhosis. In particular, we examined both the leader sequence and the B-cell immunodominant epitope, the lipoic acid domain. In addition, because patients with PBC have autoantibodies to the BCKD-E2 complex, we have quantitated plasma levels of alpha-ketoacids potentially affected in maple syrup urine disease. These include pyruvic acid (PY), phenylpyruvic acid (PP), alpha-ketoisocaproic acid (KIC) alpha ketoisovalerate (KIV) and alpha-keto-beta-methylvaleric acid (KMV). The levels of these alpha-ketoacids were compared in patients with primary sclerosing cholangitis and normal volunteers. The sequence of BCKD-E2 obtained from PBC hepatocytes showed homology with normal BCKD. Further studies of autoantigen structure and sequence are clearly indicated, including those involved in mitochondrial transport and localization. Finally, we noted a statistically significant increase in all plasma alpha-ketoacids except alpha-keto-beta methylvaleric acid in PBC patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216689 TI - Combined cyclosporin A-steroid-MTX treatment in endogenous non-infectious uveitis. AB - Thirty-two patients with endogenous uveitis resistant to treatment with high doses of cortisone and other immunosuppressive agents were treated with cyclosporin A (at an initial dose of 5 mg/kg/die, subsequently modified according to individual clinical response), fluocortolone and methotrexate. Total and lasting disease remission was obtained in all patients, together with the recovery of normal visual acuity in 20 cases and its significant improvement in the remaining 12. Furthermore, in all patients the total disappearance of all ocular inflammatory activity was observed and maintained for a period of 10.87 +/ 5.31 (6-18) months. No signs of renal or hepatic toxicity were observed in any of the patients. A form of hirsutism appeared in only two cases. PMID- 8216690 TI - Limiting dilution analysis of Epstein-Barr virus infectable B cells secreting anti-Ro/SSA and anti-La/SSB antibodies in neonatal lupus erythematosus and systemic lupus erythematosus. AB - Neonatal lupus erythematosus (NLE) is associated with the transplacental passage of maternal anti-Ro and anti-La antibodies. In order to better determine the risk of delivery of a child with NLE, we examined the frequency of anti-Ro and anti-La antibody secreting cells in mothers of children with NLE and in mothers at risk to deliver a child with NLE. We established limiting dilution experiments, using EBV-infected peripheral blood mononuclear cells, from 10 mothers following delivery of a child with NLE and from six mothers with anti-Ro and anti-La antibodies who delivered an unaffected child. Supernatants were assessed, by Poisson analysis, to determine the frequency of IgG and IgM anti-Ro and anti-La antibody-secreting B cells. We found that the frequency of anti-Ro and anti-La IgM antibody secreting B cells was greater than the frequency of IgG antibody secreting B cells of the same autoantibody specificity. We found no correlation between serum IgM and IgG anti-Ro or anti-La antibody titres and their respective precursor cell frequencies. We found that the mothers of children with NLE who later developed SLE tended to have higher anti-Ro and anti-La antibody-committed B cells than did the mothers who remained well. Although anti-Ro and anti-La antibody precursor frequencies were similar within a patient, they varied significantly from patient to patient. We found that most of the experiments with a precursor frequency of < 1 per million were from mothers of children with NLE rather than the mother with SLE who delivered normal children. Overall, we found that, in anti-Ro and anti-La antibody-positive women, a low anti-Ro or anti-La antibody B cell precursor frequency tended to be associated with the birth of a child with NLE. PMID- 8216691 TI - Elevated levels of the 90 kD heat shock protein in patients with systemic lupus erythematosus are dependent upon enhanced transcription of the hsp90 beta gene. AB - The level of the 90 kD heat shock protein (hsp90) has been shown to be elevated in the peripheral blood mononuclear cells of a subset of SLE patients. We show that this increased level of hsp90 is primarily dependent upon the enhanced transcription of the hsp90 beta gene which is observed in these patients but not in normal controls or SLE patients without elevated protein levels. Elevated transcription of the hsp90 beta gene in SLE patients is not in general paralleled by enhanced transcription of the hsp70 or ubiquitin genes indicating that the hsp90 beta gene is specifically activated in some SLE patients. PMID- 8216692 TI - IgG subclass distribution of ryanodine receptor autoantibodies in patients with myasthenia gravis and thymoma. AB - Patients with myasthenia gravis (MG) and thymoma often have autoantibodies to the ryanodine receptor (RyR), a ligand-gated Ca(2+)-release channel in the sarcoplasmic reticulum of striated muscle. Using an ELISA, we studied the Ig isotype and IgG subclass distribution of RyR autoantibodies in sera from 30 MG patients with thymoma. RyR IgG antibodies were detected in 16/30 sera. 14/30 sera had IgG1 RyR antibodies, and 15/30 sera had IgG3 RyR antibodies. All sera with IgG1 RyR antibodies also contained IgG3 antibodies. A small number of sera had low amounts of IgG2, IgG4, IgA or IgM RyR antibodies. The RyR autoantibodies are therefore mainly expressed in the IgG1 and IgG3 subclasses. The RyR autoantibodies may be of pathogenic significance by interfering with the mechanism of excitation-contraction coupling in striated muscle. PMID- 8216693 TI - Assessment of striatal extracellular dopamine and dopamine metabolites by microdialysis in haloperidol-treated rats exhibiting oral dyskinesia. AB - Rats that had received continuous, chronic haloperidol (HAL) for 32 weeks were mentioned for changes in oral movements as determined by Fast Fourier analysis of jaw movements recorded with a computerized video analysis system. Beginning at 24 weeks of administration, HAL-treated animals exhibited a pattern of significant increases in oral movement activity in the 1 to 3 Hz range and decreases in the 5 to 8 Hz range when compared to control animals. The release and metabolism of dopamine (DA) in the striatum of these animals was then assessed using intracranial microdialysis during week 32 of HAL administration and 3 days after withdrawal of HAL. Basal extracellular concentrations of the DA metabolites, 3,4 dihydroxyphenylacetic acid and homovanillic acid were significantly increased in the HAL-treated rats during continuous HAL administration. Three days after withdrawal from HAL, no difference was seen in basal extracellular concentrations of any of the analytes. No difference in the magnitude of DA release was seen between groups following local application of amphetamine (10 microM) through the dialysis probe during or after chronic HAL administration. These results confirm previous findings that long-term HAL administration produces increased DA turnover during HAL administration, but that this increase does not persist following HAL withdrawal. The increased striatal DA turnover seen during chronic HAL administration may have relevance to the development of late-onset neuroleptic-induced dyskinesia in rats. PMID- 8216694 TI - Tissue concentrations of clozapine and its metabolites in the rat. AB - Clozapine (CLZ) and its metabolites norclozapine (NOR) and clozapine-N-oxide (NOX) were assayed in rat serum and brain tissue after intraperitoneal injection of CLZ. Clozapine levels rose with dose, averaging 28 ng/ml (87 nmol/L) serum per milligram/kilogram dose. Brain- and serum-CLZ levels correlated closely, averaging 24-fold higher in brain. Norclozapine and NOX averaged approximately 58% and 13% of CLZ in serum, respectively, whereas in brain, NOR was detected only at doses greater than or equal to 10 mg/kg (approximately 5.6% of CLZ) and NOX was undetectable. Levels peaked within 30 minutes, and elimination of CLZ from brain and CLZ or NOR from blood was very rapid (half-life = 1.5 to 1.6 hours). A week of daily dosing with CLZ led to no accumulation of drug in brain; a week of fluoxetine pretreatment increased analyte concentrations (serum, 86%; brain, 61%), but valproate had little effect. PMID- 8216695 TI - Low plasma GABA is a trait-like marker for bipolar illness. AB - Plasma gamma-aminobutyric acid (pGABA) is an index of brain GABA activity and a peripheral marker of mood disorder. Previous research has indicated that pGABA is abnormally low in approximately 40% of patients symptomatic with primary unipolar depression. We have now measured pGABA in a series of patients with bipolar disorder. Blood samples for GABA determinations were collected soon after admission to hospital or clinic while patients were symptomatic. In both manic and depressed phase bipolar patients, mean levels of pGABA were significantly lower than in healthy control subjects. The distribution of pGABA in bipolar patients, whether manic or depressed, was similar to that in symptomatic unipolar depression, with 30% to 40% having pGABA levels lower than the control range. These data indicate that low pGABA is not specific to the depressed state, as it is also found in the manic phase of bipolar disorder. Low pGABA may represent a shared biologic correlate between bipolar and unipolar illness. PMID- 8216696 TI - Clomipramine administered during the luteal phase reduces the symptoms of premenstrual syndrome: a placebo-controlled trial. AB - In a previous controlled trial we have shown that premenstrual irritability and depressed mood (premenstrual syndrome) can be effectively reduced by low doses of the potent (but nonselective) serotonin reuptake inhibitor clomipramine taken each day of the menstrual cycle. The present study was undertaken to examine to what extent intermittent administration of clomipramine, during the luteal phase only, is also effective against premenstrual complaints. Twenty-nine nondepressed women displaying severe premenstrual irritability and/or depressed mood and fulfilling the DSM-III-R criteria of late luteal phase dysphoric disorder were treated daily from the day of ovulation until the onset of the menstruation either with clomipramine (25 to 75 mg) (n = 15) or with placebo (n = 14) for three consecutive menstrual cycles; another nine subjects (seven on clomipramine, two on placebo) dropped out during treatment. In both treatment groups self-rated premenstrual irritability and depressed mood (as registered daily using a visual analogue scale) were significantly reduced during treatment; in the placebo group, this symptom reduction was about 45%, whereas in the clomipramine group it was greater than 70%. The mean premenstrual ratings of irritability and depressed mood during the three treatment cycles were significantly lower in the clomipramine group than in the placebo group. Also with respect to the rating of global improvement, the result obtained with clomipramine was significantly better than that obtained with placebo. The study confirms the previously reported effectiveness of low doses of clomipramine in the treatment of premenstrual syndrome and demonstrates that the time lag between onset of medication and clinical effect is shorter when clomipramine is used for premenstrual syndrome than when it is used for depression, panic disorder, or obsessive compulsive disorder. PMID- 8216697 TI - Developmental differences in acute nigrostriatal and mesocorticolimbic system response to haloperidol. AB - Dose-dependent effects of haloperidol (2.66 nmol/kg to 79.8 mmol/kg, IP) on levels of dopamine, homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) were assessed in the corpus striatum, nucleus accumbens, and medial prefrontal cortex (PFCTX) of 18-, 30-, and 110-day-old rats. Eighteen-day-old rats were 35% and 63% more sensitive than adults to the effects of haloperidol on striatal and accumbens turnover and had steeper dose-response curves. The dose response function in the PFCTX was similar to striatum at 18 days, but became shallower and nonsigmoidal with age. Maximally effective doses of haloperidol produced, at all ages, a comparable percent rise in DOPAC levels in all regions. With maturation, the percent rise in HVA progressively outstripped DOPAC response in nucleus accumbens and striatum. Overall, prominent developmental differences emerged in these regions in their sensitivity and response to haloperidol, which are consistent with previously reported differences in behavioral sensitivity. PMID- 8216698 TI - Low versus high prolactin responders to fenfluramine challenge: marker of behavioral differences in adult male cynomolgus macaques. AB - Prolactin response to acute administration of fenfluramine hydrochloride is considered an indirect assessment of "net" central serotonergic activity. This study compared behavioral characteristics of adult, male cynomolgus macaques (Macaca fascicularis) having "low" or "high" prolactin responses to fenfluramine challenge. The subjects were 75 animals housed in five-member social groups for 28 months. In month 23, prolactin responses to fenfluramine challenge were evaluated. Observations of specific behaviors (aggressive, submissive, affiliative, and nonsocial) were made three times per week on animals in each social group. The dominance status of each animal within a social group was assessed at weekly intervals. Low prolactin responders had a significantly higher index of "overt" aggression (ratio of fights involving physical contact and chasing or lunging/all forms of aggressive behavior) compared to high prolactin responders (p < .03). There were no differences in the dominance status of low and high responders (p = .34). Furthermore, low responders were more socially withdrawn than high responders, as they spent significantly more time alone (passive or neutral state; p < .03) and less time in passive body contact with other animals than high responders (p < .05). These data support the hypothesis that reduced central serotonergic activity in nonhuman primates is associated with a high level of overt aggression and a low level of positive social interaction. PMID- 8216699 TI - Effect of prostaglandin E1 on preservation injury of canine liver grafts preserved in UW solution. AB - This study investigated whether prostaglandin E1 (PGE1) could reduce hepatic injury to the liver graft caused by harvesting and 24-h preservation in University of Wisconsin (UW) solution in a canine model. The PGE1-treated group was intravenously administered 0.5 microgram/kg per minute of PGE1 for 30 min before harvesting, as well as a concentration of 1 mg/l PGE1 in the washout and UW solutions. In both the PGE1-treated and the control group, all recipients survived for 1 week or more after transplantation. Arterial ketone body ratio (AKBR) remained over 1.0 in the early postoperative period. The PGE1 group showed significant reductions in guanase, GOT, and LDH during the early postoperative period compared to the untreated control group. Histological examination disclosed partial mitochondrial swelling, hepatocyte vacuolation, and necrosis in the control group, while such abnormalities were rarely seen in the PGE1 group. These results suggest that PGE1 can effectively reduce hepatic injury to liver grafts preserved in UW solution prior to transplantation. PMID- 8216700 TI - Effect of platelet-activating factor (PAF) receptor blockers on smooth muscle cell replication in vitro and allograft arteriosclerosis in vivo. AB - Platelet-activating factor (PAF) stimulates smooth muscle cell (SMC) replication both in vivo and in vitro. In this study we have investigated whether PAF receptor-blocking molecules modulate SMC replication in vitro and the generation of allograft arteriosclerosis in vivo. SMC cultures were established from baby rat aorta media and fibroblast control cultures from the adventitia. Identification of the cultured cell types was determined both by immunohistochemistry and electron microscopy. Both cell types replicated in culture with 10% fetal calf serum (FCS). The addition of PAF-C18 enhanced, and the addition of three PAF receptor inhibitors--WEB 2086, WEB 2170, and BN 50739- reduced, SMC replication and protein synthesis in a dose-dependent fashion in vitro until toxic concentrations were reached. The most potent of these drugs, WEB 2170, was then delivered at the rate of 12 mg/kg per day to recipients of rat aortic allografts. The responses were quantitated by autoradiography after short term labeling of the recipients with tritium-labeled thymidine (3H-TdR) and by quantitative morphology. Administration of the PAF receptor blocker had no impact on the replication of the inflammatory cells in the allograft adventitia nor on the replication of SMCs in the media and intima. Administration of the PAF receptor blocker delayed the generation of allograft arteriosclerosis slightly, but not significantly. These results suggest that PAF is not an essential component in the inflammatory cascade leading to allograft arteriosclerosis. PMID- 8216701 TI - Relevance of tumor necrosis factor to graft-versus-host disease after small bowel transplantation. AB - The small bowel (SB), an organ replete with lymphocytes, may provoke graft-versus host disease (GVHD) after transplantation (Tx). Since tumor necrosis factor (TNF) has been suspected of mediating the tissue lesions of GVHD, we sought to determine whether TNF could be detected in the serum of rats undergoing GVHD after SBTx or lymphocyte transfer. For this purpose, postoperative serum TNF activity was determined in Lewis x Brown Norway (LBNF1) hybrid rats suffering from GVHD after undergoing transplantation of an entire (group 1; n = 8) or a segmental (group 2; n = 4) Lew SB, or after i.p. injection with lethal doses (500 x 10(6)) of Lew lymphocytes (group 3; n = 3). Control LBNF1 received i.p. small doses (50 x 10(6)) of Lew lymphocytes (group 4; n = 4). Serum TNF activity was assessed using the WEHI bioassay. In rats with acute and lethal GVHD after entire SBTx (group 1) or injection with large doses of lymphocytes (group 3), TNF activity gradually increased and reached high levels by the time the rats were agonal. In segmental SBTx rats (group 2), GVHD was less severe than in entire SBTx rats. Similarly, the increase in TNF activity was less intense and only transient since it had returned to control levels by the time the rats had completely recovered from GVHD. In control rats primed with small doses of lymphocytes (group 4), GVHD did not occur and no increase in TNF activity was detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216702 TI - Scintigraphic imaging of MHC class II antigen induction in mouse kidney allografts: a new approach to noninvasive detection of early rejection. AB - Mice with kidney transplants were investigated to determine whether early kidney allograft rejection could be detected by radioimmune scintigraphy targeting major histocompatibility complex (MHC) class II antigens induced on donor organ cells. Allografts from C3H/He (H2k) donors were transplanted into BALB/c (H2d) recipients. Each mouse was injected intravenously with 100 microCi of 123I labeled anti-MHC class II monoclonal antibody (mAb; Y17, anti-IEk) 16 h before scintigraphy. After imaging, mice were sacrificed for tissue counting and histopathological examination. Radiotracer uptake in the nontreated allografts increased starting on the 3rd day after transplantation, peaked at around the 6th day, and then gradually decreased. Rejecting allografts with only focal perivascular mononuclear cell infiltration could be identified by scintigraphy. However, allografted mice without evidence of rejection and isografted mice did not show an increase in radiotracer uptake. Rejecting BALB/c kidney transplanted into C3H/He mice did not show an increase in Y17 mAb uptake, suggesting that class II antigens induced on donor kidneys are solely responsible for the mAb uptake in positive scintigrams of rejecting allografts. Five allografted mice were treated with anti-CD3 mAb and cyclosporin starting 3-9 days after transplantation. Radiotracer uptake decreased after 4 weeks of treatment and increased 2 weeks after the cessation of immunosuppressive treatment, reflecting suppression and recurrence of rejection, as determined by histological examination. These changes could be followed scintigraphically. We conclude that changes in class II antigen expression can be assessed by the 123I-labeled anti MHC class II antigen mAb and that it is a sensitive and noninvasive method for detecting kidney allograft rejection. PMID- 8216703 TI - The role of early baseline computed tomography in the interpretation of morphological changes after kidney-pancreas transplantation. AB - In a prospective study, 17 early baseline computed tomography (CT) scans were obtained 2 or 3 days after simultaneous kidney-pancreas transplantation. Morphological changes and their relevance to the early detection of graft rejection and complications were evaluated. The pancreatic grafts were enlarged and showed signs of mild pancreatitis. Serial scans obtained during the first renal graft rejection episode were compared with the baseline CT scans (n = 7). They showed a significant increase in pancreatic graft size in the case of biopsy proven severe renal graft rejection (P = 0.008). Normally functioning pancreatic allografts showed a 15%-40% decrease in size 1-6 months after transplantation. We conclude that the morphological changes observed early after transplantation are compatible with mild pancreatitis, which may contribute to the development of pancreatic graft thrombosis. There is an increase in the number of morphological changes during severe rejection, yet enlarged pancreatic grafts appear to recover from transplantation-related damage and regain their normal size without signs of atrophy. PMID- 8216704 TI - A highly sensitive, rapid screening method for the detection of antibodies directed against HLA class I and II antigens. AB - Screening of potential transplant recipients for antibodies that can cause graft rejection is an essential part of the pre-transplant monitoring carried out by tissue typing laboratories. This is a time-consuming process and the rapid reporting of results is dependent on the maintenance of frozen cell panels. The usual procedure of screening against a panel of random cells takes up to 6 weeks. In this study we have used flow cytometric analysis of pooled chronic lymphatic leukaemia (CLL) cells to detect antibodies directed against HLA antigens. We show that FACS screening of pooled cells can accurately and rapidly detect these antibodies and that the method is suitable for routine use. An estimate of the degree of patient panel reactivity can be determined within a few hours. In addition, the technique is more sensitive than those conventionally used, an advantage that may be of importance in preventing graft damage. PMID- 8216706 TI - Failure of acyclovir to prevent cytomegalovirus infection in renal allograft recipients. AB - Cytomegalovirus (CMV) is the most common opportunistic pathogen following renal transplantation and remains a major concern in transplantation centers owing to its high morbidity and impact on renal allografts. Pending more effective antiviral drugs, efforts have been directed toward prevention strategies. We conducted a retrospective analysis to evaluate the efficacy of various prophylactic options used at our institution during the period April 1986 to August 1990. All CMV-negative patients with CMV-negative kidneys (D-R-) received screened, CMV-negative blood products (n = 19). CMV-specific immunoglobulins (CMV Ig) were used in 6 patients at increased risk for primary CMV infection and acyclovir was administered to 21 patients at an initial intravenous dose of 5 mg/kg body weight; then oral doses of 800-3200 mg per day were given according to the patients' estimated creatinine clearance. Thirty-two patients did not receive any CMV prophylactic treatment and served as controls. CMV monitoring of the patients during the first 6 months after transplantation showed an overall infection and disease rate of 81% and 38.1%, respectively, in the acyclovir treated group. Compared with controls, the incidences of infection and disease were higher in the acyclovir-treated patients, with a significant difference for CMV infection (P = 0.002, generalized Wilcoxon test). Only 1 of the 19 D-R- patients presented with CMV infection. CMV Ig-treated patients tended to have less severe disease without any apparent reduction in infection incidence. Given the high rate of infection in patients at risk, we infer that high-dose acyclovir does not prevent CMV infection in our setting of renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216707 TI - Long-term effects of steroid withdrawal in kidney transplantation. AB - The long-term graft function after withdrawal of steroids from maintenance immunosuppression was analyzed in 98 kidney recipients (59 on cyclosporin monotherapy, 39 on cyclosporin plus azathioprine) who had not developed an early rejection episode when prednisolone was discontinued. Seven years after steroid withdrawal the probability of an increase in serum creatinine (> 20% of baseline levels) was 51%. The increase in creatinine was associated with sclerosing arteriopathy as a marker of chronic rejection in 29 of 43 graft biopsies. The addition of azathioprine had no effect on the stability of long-term graft function and did not influence the 7-year graft survival rate in this highly selected group of patients. PMID- 8216705 TI - Protective effects of the lazaroid U74500A and lidoflazine on liver preservation with UW solution. AB - The effect of adding a 21-aminosteroid, U74500A, and a Ca2+ antagonist, lidoflazine, alone and together to UW solution was assessed in a rat liver preservation model. Following preservation, the livers were reperfused using a closed circuit, and the release of hepatocellular enzymes (ASAT, ALAT, and LDH) into the perfusate was determined with increasing time. Both drugs reduced the amount of enzymes lost from the liver. The combination of the two drugs was better than either drug alone. These data suggest that both agents may be of value in organ preservation for clinical liver transplantation. PMID- 8216708 TI - Surgical results of left lobectomy and left hepatectomy in 70 noncirrhotic patients. A preliminary evaluation before performing liver transplantation from living related donors. AB - As a preliminary step before performing liver transplantation using living related donors, a comparative study was undertaken to determine the specific operative risk of left lobectomy (n = 54) compared to left hepatectomy (n = 16) in noncirrhotic patients. No postoperative death was observed in either group and no patients required reoperation. The mean hospital stay was longer after left hepatectomy than after left lobectomy (23 +/- 15 days vs 10 +/- 3 days, P < 0.05). The postoperative course was uneventful in 94% of the patients after left lobectomy and in 44% after left hepatectomy (P < 0.001). The peroperative transfusion rate was higher after left hepatectomy than after left lobectomy (38% vs 4%, P = 0.001). The postoperative collection rate was higher after left hepatectomy than after left lobectomy (25% vs 6%, NS). No biliary fistulas or subphrenic abscesses were noted after left lobectomy; however, these were observed in 19% and 12% of the cases, respectively, after left hepatectomy. Although conventional liver resection is quite different from graft harvesting in living related transplantation, our study demonstrates that the morbidity rate is significantly higher after left hepatectomy than after left lobectomy. PMID- 8216709 TI - The pattern of rejection after combined stomach, small bowel, and pancreas transplantation in the rat. AB - This study was designed to investigate whether in combined stomach, small bowel, and pancreas transplantation allograft rejection occurs in the individual organs concomitantly and with the same intensity. Heterotopic en-bloc transplantation of the stomach, small bowel, and pancreas was performed in a Lewis-to-Brown Norway rat combination. Group 1 animals received no immunosuppressive therapy while animals in group 2 were treated with cyclosporin (10 mg/kg body weight, orally) daily. Grafts were histologically evaluated on the 5th (subgroups 1a and 2a) and 10th (subgroups 1b and 2b) postoperative days. The degree of rejection was defined as moderate, intermediate, or severe according to predefined criteria. The results indicate that the small bowel is more susceptible to rejection than either the stomach or the pancreas. Mucosal biopsies of the stomach are unlikely to provide a reliable guide to rejection in the small bowel. PMID- 8216710 TI - Side-to-side cavo-cavostomy: a useful aid in "complicated" piggy-back liver transplantation. AB - Piggy-back liver transplantation is a useful technical variant of orthotopic liver transplantation. Its success can, however, be compromised by severe stenosis or obstruction of the recipient's inferior vena cava at the level of the anastomosis. A technique is described--side-to-side cavocavostomy--to resolve this difficult intraoperative situation. PMID- 8216711 TI - Simultaneous kidney-pancreas transplantation using a horseshoe kidney. PMID- 8216712 TI - Comparison of bovine immune responses to affinity-purified bovine herpesvirus-1 antiidiotypes and glycoproteins. AB - Bovine immune responses to rabbit antiidiotypic antibodies (anti-Id) against neutralizing monoclonal antibodies to bovine herpesvirus-1 (BHV-1) envelope glycoproteins and to BHV-1 glycoproteins were compared. Glycoprotein-immunized animals produced high titers of anti-BHV-1 antibodies and were protected against BHV-1 challenge. Recombinant bovine interleukin-2 (rIL-2)-treated, anti-Id immunized animals showed a slight reduction in clinical disease, and one calf produced BHV-1-neutralizing antibodies. Treatment with rIL-2 augmented non-BHV-1 specific immune responses. However, even with rIL-2 as an adjuvant, the mixture of polyclonal anti-Id did not elicit a consistent, protective BHV-1-specific immune response in calves. PMID- 8216713 TI - Infectious immune complexes in HIV-1-infected patients. AB - Using polyethylene glycol (PEG) precipitation we have found that most HIV-1 seropositive patients have IgG containing-circulating immune complexes (CIC). In addition these CIC sometimes contain IgA, IgM, C3, and/or HIV p24 antigen. Previous work has demonstrated that patients who have plasma viremia, CD4 cell counts less than 170/mm3, or who are symptomatic are more apt to have HIV that is precipitable with PEG. In this study we report that the infectious HIV found in the plasma of patients with plasma viremia could only be found in the 2% PEG precipitates, i.e., PEG supernatants never contained infectious HIV, although they often contained noninfectious p24 antigen. These results suggested that at least some of the infectious HIV circulating in the plasma of infected patients is in the form of immune complexes. To support this idea we also demonstrated that infectious HIV could be precipitated with antiserum raised to either immunogloblins or complement components. PMID- 8216714 TI - Lysis of human arterial smooth muscle cells infected with herpesviridae by peripheral blood mononuclear cells: implications for atherosclerosis. AB - The cytotoxicity of peripheral blood mononuclear cells (PBMC) to human arterial smooth muscle cells (SMC) infected with cytomegalovirus (CMV) or herpes simplex virus-1 (HSV) was investigated. PBMC were isolated from heparinized blood of healthy donors by Ficoll-Hypaque centrifugation and were tested for cytotoxicity against human SMC or human fibroblast-like (MRC-5) cells infected with CMV or HSV, using the chromium-51 (51Cr) release cytotoxicity assay. Both SMC and MRC-5 cells infected with either CMV (SMC-CMV), (MRC-5-CMV), or HSV (SMC-HSV), (MRC-5 HSV) were lysed by PBMC above background lysis of uninfected SMC cells. Treatment of PBMC with NK-specific monoclonal CD16 antibody and rabbit complement reduced greatly the lysis of SMC, SMC-CMV, and K562 cells, suggesting that lysis of different types of target cell by PBMC was mediated mainly by natural killer (NK) cells. The pattern of natural cytotoxicity against SMC-CMV was different from that against SMC-HSV. Maximum lysis of SMC-CMV was observed at 24 hr postinfection compared to 8 hr postinfection for SMC-HSV. NK reactivity against SMC-CMV increased from 8 to 24 hr postinfection, followed by a gradual decline at 48 and 72 hr. Supernatants generated by culturing SMC-CMV or coculturing SMC-CMV with PBMC enhanced NK cell-mediated lysis of SMC or SMC-CMV. Natural cytotoxic reactivities of PBMC against SMC-CMV or SMC-HSV may occur in vivo. Such reactions could moderate the interaction of these viruses with vascular SMC and could influence the development and/or the progression of atherosclerotic lesions. PMID- 8216715 TI - New enzyme immunoassays for the serologic detection of woodchuck hepatitis virus infection. AB - The woodchuck and the woodchuck hepatitis virus (WHV) have been used as a model of hepatitis B virus infection and its disease sequelas. Serologic responses to WHV infection have been described in previous reports from this laboratory by using virus-specific radioimmunoassays (RIAs) for WHV surface antigen, antibody to WHV core antigen, and antibody to WHsAg. In this study, we developed and evaluated new enzyme immunoassays (EIAs) for these WHV serologic markers. Relative to the established RIAs, the EIAs were either improved or comparable in their sensitivity and specificity, and in their utility for monitoring experimental WHV infection and classifying woodchucks into serological diagnostic categories. These EIA systems are amenable to the quantitative titration of antibodies and quantitation of WHV antigens in serum, and ultimately should allow improved resolution of virologic and humoral immune responses of woodchucks to WHV infection. PMID- 8216716 TI - Detection of two early gene products of Epstein-Barr virus by fluorescence flow cytometry. AB - The intracellular expression of two early gene products of Epstein-Barr virus (EBV) was evaluated by fluorescence flow cytometry. Two Burkitt's lymphoma cell lines were superinfected by EBV from the P3HR-1 cell line. Twelve to 96 hr after superinfection the cells were fixed with paraformaldehyde and made permeable by saponin treatment. Monoclonal antibodies to the diffuse (D) and restricted (R) components of the early antigen (EA) complex were applied to the cells followed by fluorochrome-conjugated goat antibodies specific for the heavy chain isotypes of the monoclonal antibodies. Fluorescence flow cytometry revealed a clear separation in fluorescence intensity between cells containing EA-R or EA-D and negative cells. A major proportion of EA-positive cells displayed both antigens. In addition, a significant fraction expressed either EA-R or EA-D but not both. Expression of EA occurred more rapidly and peaked earlier in Daudi cells than in Raji cells. This apparent difference in EA expression between the two cell lines, however, was much less pronounced when one considered the proportion of cells expressing EA-R only, EA-D only, or both EA-R and EA-D, as a percentage of the total EA expression. Parallel fluorescence microscopy experiments revealed that the variation of the ratio of EA-R to EA-D expression with time correlated well between the two methods. PMID- 8216717 TI - Nursing in action. Strengthening nursing and midwifery to support health for all. PMID- 8216718 TI - Safety and efficacy of therapeutic monoclonal antibodies in clinical therapy. PMID- 8216719 TI - Defining criteria for autoimmune diseases (Witebsky's postulates revisited) AB - With new knowledge gained from molecular biology and hybridoma technology, as well as the original Witebsky postulates, we propose that three types of evidence can be marshalled to establish that a human disease is autoimmune in origin. They include direct evidence from transfer of pathogenic antibody or pathogenic T cells; indirect evidence based on reproduction of the autoimmune disease in experimental animals; and circumstantial evidence from clinical clues. PMID- 8216720 TI - A three-tiered view of the role of IgA in mucosal defense. AB - Mucosal IgA has generally been viewed as an immune barrier to prevent the adherence and absorption of antigens. Recent studies employing polarized epithelial monolayers have suggested two additional functions for mucosal IgA. One is to neutralize intracellular microbial pathogens, such as viruses, directly within epithelial cells. The second is to bind antigens in the mucosal lamina propria and excrete them through the adjacent epithelium into the lumen, thereby ridding the body of locally formed immune complexes and decreasing their access to the systemic circulation. PMID- 8216721 TI - HIV and human complement: mechanisms of interaction and biological implication. AB - Human complement, although not lytic for HIV-1, interacts with the virus and is closely involved in the infectious process. It enhances infection in the absence of antibody, and turns neutralizing antibodies into agents which increase viral infectivity. In this review M.P. Dierich et al. summarize available information and discuss possible biological implications. PMID- 8216722 TI - An immunologist's look at the Rho and Rab GTP-binding proteins. AB - The ras superfamily of small GTP-binding proteins contains three major branches: the Ras, Rho and Rab protein subfamilies. Recent advances in the field of ras related small GTP-binding proteins suggest that it may be worthwhile to look at this superfamily from the standpoint of immunology. The subject of this review is to outline briefly the areas of lymphocyte function which may implicate small G proteins, with special emphasis on the established or possible roles of proteins of the Rho and Rab subfamilies in cytoskeleton organization and antigen presentation. PMID- 8216723 TI - The thymic microenvironment. PMID- 8216724 TI - Is TCR beta expression an essential event in early thymocyte development? AB - The evolution of a T cell through the thymus is characterized by several distinct morphological changes. The underlying mechanisms allowing a double negative thymocyte to mature to a double positive one expressing both CD4 and CD8 are still hazy. Here, Donald Palmer, Adrian Hayday and Michael Owen discuss the latest development in the field and data that underscore the crucial role of TCR components in the transition of double negative to double positive thymocytes. PMID- 8216725 TI - Development in the thymus: it takes two to tango. AB - Intrathymic T-cell development is dependent upon signals provided by the thymic stromal cell microenvironment. However, loss of thymic T cells in natural and experimentally induced situations is associated with a reduction in the surrounding epithelium, suggesting an interdependence between thymocytes and their microenvironment. Here, the authors review the evidence in favour of this intrathymic symbiosis, and hypothesize that T cells may provide maturation and survival signals that are necessary for the development and maintenance of their microenvironment. PMID- 8216726 TI - Heidikines. PMID- 8216727 TI - Lymphocyte lifespans revisited. PMID- 8216728 TI - [The complement system]. AB - After its discovery, about 100 years ago, complement was described as a cytotoxicity effector, the "armed hand" of antibodies. Since the description of an "alternate" pathway of activation, independent of antigen-antibody reactions, this restrictive concept has been modified. It has been progressively revealed to be a system that is composed of many proteins and our understanding of their biological roles has become much more developed. Nowadays, it is especially considered as a means for the body to generate peptides that regulate many functions: phagocytosis, antibody synthesis, inflammatory reactions, photosensitisation, coagulation, etc. Discovery of components, not only in the vehicles of serum or the other biological fluids but also associated with the cell membrane, has greatly increased the regions of action. Finally, progress in genetics, particularly in nucleic acid sequencing, has revealed families of proteins, a priori not apparent, that are analogues of the sequences and take part in the function of very varied areas. The roles of complement are thus not restricted only to immunological mechanisms, but they extend into many areas of biology and physiology. PMID- 8216729 TI - [Proteolytic enzymes and their inhibitors]. AB - Tryptase (T), chymase (C), carboxypeptidase A, cathepsin G-like constituent of preformed mediators contained in mastocyte granules, are a group of neutral proteases with proteolytic activity. These enzymes gives differentiation of two groups of mastocytes, MCTC and MCT as a function of the richness of enzymes. Although the functions of these molecules are becoming better and better understood, their exact roles as well as that of their inhibitors, still remain to be explored in urticaria. PMID- 8216730 TI - [Role of endothelial activation in urticaria]. AB - The endothelial cells, because of their privileged situation between the tissues and the vessels, play an important role in the inflammatory reaction. Expression of adhesion molecules (ELAM 1 especially) allows adhesion of circulating neutrophils to the epithelial cell and thus initiates the reaction. During the reactions of immediate hypersensitivity, the flow of leucocytes observed in the late phase is dependent on mastocytes, the recruitment being under the positive or negative influence of several cytokines. PMID- 8216731 TI - Mutational specificities of environmental carcinogens in the lac1 gene of Escherichia coli, VII: The host-mediated assay and its comparison with in vitro mutagenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. AB - To investigate the influence of different types of metabolic activation (9,000 x g supernatant (S9) activation vs. a host-mediated approach) on 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced mutational specificity, we determined by DNA sequencing the distribution of forward mutations recovered in the N-terminal region of the lac1 gene of Escherichia coli. After activation with the S9 liver fraction from rats treated with Aroclor 1254, a diverse spectrum of mutations was recovered, with 55% of the events being G:C-->A:T transitions. In contrast, after the host-mediated assay in mice, G:C- >A:T transitions accounted for over 94% of the mutations recovered. Generally, NNK metabolism can proceed through two distinct pathways, involving either alpha methyl or methylene hydroxylation. These two pathways produce different distributions of DNA damage. The difference in the mutational spectra we observed thus likely reflects the difference in the contributions of each pathway under the two different treatment conditions. PMID- 8216732 TI - Loss of heterozygosity: the most frequent cause of recessive phenotype expression at the heterozygous human adenine phosphoribosyltransferase locus. AB - Expression of a recessive phenotype can occur by a number of different mechanisms, such as chromosomal deletion, recombination, and intragenic frameshift mutation or base substitution. To examine the contribution of different mutational events, we isolated and characterized a human fibroblast cell line heterozygous at the adenine phosphoribosyltransferase (APRT) locus. Cells that subsequently lost APRT activity were selected, cloned, and analyzed for the mechanisms contributing to the loss of APRT activity. Loss of APRT activity occurred at a rate of 7.8 x 10(-5) per allele per cell generation. Molecular analysis of DNA from 21 independent APRT- clones demonstrated that 62% of mutants had lost the functional allele and that the rest had incurred intragenic mutations. Loss of the functional allele was frequently accompanied by loss of the proximal marker D16S77 but not the more distant proximal marker D16S4, indicating that a high frequency of mitotic recombination or deletion occurred at the region between D16S77 and D16S4 on chromosome 16. Loss of APRT activity in the remaining 38% of the clones was predominantly due to point mutations. These data demonstrate that the mechanisms for loss of heterozygosity at the APRT locus are similar to those found in retinoblastoma and other tumors. The autosomal location of the APRT gene and the ease with which its phenotype can be selected make this gene useful for modeling mutational events at loci important to carcinogenesis. PMID- 8216733 TI - Mutagenic specificity of the (+)anti-diol epoxide of dibenz[a,j]anthracene in the supF gene of an Escherichia coli plasmid. AB - This study was designed to examine the mutagenic specificity of (+)anti dibenz[a,j]anthracene 3,4-diol-1,2-epoxide ((+)anti-DB[a,j]A-DE) in SOS-induced repair-proficient Escherichia coli ES87 (delta pro-lac, strA)/F' (pro+, lac1Q, lac1am26, lacZ delta M15). The plasmid pUB3, which contains the mutation target gene, supF, was modified with (+)anti-DB[a,j]A-DE in vitro (two to five adducts/plasmid) and then transformed into bacteria by electroporation. The spontaneous mutation frequency for unmodified pUB3 in uninduced cells was about 2 x 10(-6) and for SOS-induced cells, about 8 x 10(-6). The spontaneous supF- mutations were primarily insertions, deletions, and frameshifts. The mutation frequency for (+)anti-DB[a,j]A-DE-modified pUB3 was about 8 x 10(-6) and about 32 x 10(-6) for uninduced cells and SOS-induced cells, respectively. (+)anti DB[a,j]A-DE induced primarily point mutations in supF in SOS-induced cells. GC- >AT transitions were the major mutations observed in SOS-induced cells (37%). GC- >TA (21%) and GC-->CG (8.6%) transversion mutations were also observed, whereas mutations at AT base pairs were rare (1.9%). Furthermore, a large number of tandem GC/GC-->AT/AT transition mutations were also observed (about 15% of all mutations in SOS-induced cells). Taken together, single and tandem GC-->AT mutations accounted for slightly over half (about 51%) of the mutations observed in SOS-induced cells. These results demonstrated that (+)anti-DB[a,j]A-DE was mutagenic in repair-proficient E. coli; however, unlike other polycyclic aromatic hydrocarbons that induce primarily transversion mutations, (+)anti-DB[a,j]A-DE caused mostly GC-->AT transitions. PMID- 8216734 TI - Genetic analysis of carcinogen enhancement of type 5 adenovirus transformation of cloned Fischer rat embryo fibroblast cells. AB - Pretreatment of CREF cells with methyl methanesulfonate (MMS) before infection with the host-range cold-sensitive type 5 adenovirus (Ad5) mutant H5hr1 results in a dose-dependent carcinogen enhancement of viral transformation (CET). The properties of CET observed with H5hr1, which include both an MMS dose-dependent enhancement in the number of transformed foci and an increase in transformation frequency after correction for cell toxicity, are not observed in carcinogen pretreated wild-type (wt) Ad5 (H5wt)-infected CREF cells. This study was conducted to determine the role of the viral E1A and E1B transforming genes of H5hr1 in mediating the unique CET phenotype of H5hr1. Coinfection of MMS pretreated CREF cells with H5wt or H5sub309 (which displays a wt Ad5 phenotype) and H5hr1 resulted in a suppression of the unique CET phenotype that was directly related to the multiplicity of infection with wt Ad5. Suppression of the unique H5hr1 CET phenotype was also apparent in MMS-pretreated CREF cells coinfected with H5hr1 and an Ad5 mutant expressing either a wt 13S E1A-encoded 289 amino acid (aa) protein and an intact wt E1B gene or a wt 13S E1A-encoded 289-aa protein and a 22S E1B-encoded 495-aa protein. In contrast, the unique H5hr1 CET phenotype was not suppressed in MMS-pretreated CREF cells coinfected with H5hr1 and Ad5 or Ad2 mutants expressing either a wt 12S E1A-encoded 243-aa protein and both wt E1B gene products or an intact wt E1A gene and a wt E1B 13S-encoded 175 aa protein. That genetic changes in both the E1A and E1B viral regions of H5hr1 were required to induce the unique CET phenotype was also indicated by the inability of a recombinant Ad5 containing the 0-4.5 map-unit region of H5hr1 and the 4.5-100 map-unit region of H5sub309 to display the H5hr1 unique CET phenotype. Direct confirmation of the requirement for both gene regions of H5hr1 to mediate its unique CET was obtained by generating CREF cells stably expressing a wt Ad5 E1A 13S-encoded 289-aa protein and a wt E1B 22S-encoded 495-aa protein. In these CREF transformants (which displayed a CREF-like morphology), transformation by H5hr1 was not reduced, but the unique CET phenotype after MMS pretreatment was eliminated. These results suggest that alterations in both the 13S-encoded E1A and 22S-encoded E1B gene products of H5hr1 contribute to its unique CET. PMID- 8216735 TI - Modulation of pp60v-src and pp60c-src expression in Rous sarcoma virus transformed hamster fibroblasts transfected with activated N-ras. AB - Three phenotypically different hamster cell lines transformed with Rous sarcoma virus (RSV) were transfected with plasmid DNA containing an activated N-ras oncogene, and nine clones expressing various levels of p21N-ras were characterized. We examined the effects of p21N-ras on expression and kinase activity of resident src proteins by using a variety of assays that allowed us to discriminate between viral and cellular src proteins. In eight clones with a 10- to 20-fold increase in p21N-ras levels relative to the endogenous protein, we observed a marked reduction in the synthesis and kinase activity of p60v-src. This decrease correlated with transcriptional downregulation of RSV genomic and v src subgenomic mRNAs. In the same cells, we found a concomitant accumulation of p60c-src and, accordingly, an increase in its protein kinase activity without an apparent increase in c-src mRNA levels. Therefore, modulation of viral and cellular src proteins in cells overexpressing p21N-ras appeared to result from two distinct effects: a downregulation of long terminal repeat-driven transcription and a more complex interaction with cellular effectors that control the stability of p60c-src. Such modulation also seemed to depend on the levels of p21N-ras and, possibly, on host-cell factors, since it was not observed in the third cell line, in which the relative increase in p21N-ras was only 2.5-fold to fivefold. PMID- 8216736 TI - Comparison of pulmonary O6-methylguanine DNA adduct levels and Ki-ras activation in lung tumors from resistant and susceptible mouse strains. AB - The role of O6-methylguanine (O6MG) DNA adduct formation and persistence in the formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumors from resistant C57BL/6 and susceptible A/J mice was investigated. In addition, the frequencies of pulmonary tumor formation and Ki-ras activation were defined in C57BL/6 mice treated with NNK or vinyl carbamate (VC), and the role of the p53 gene in pulmonary carcinogenesis in these resistant mice was examined. One day after treatment with 100 mg/kg NNK, O6MG adduct concentrations were twofold to eightfold higher in Clara cells and type II cells than in small cells or whole lungs from both mouse strains. The concentrations of O6MG in isolated cells decreased at a similar rate in the two strains of mice. Lung tumors were detected by 27 mo of age in 18% of the C57BL/6 mice after a single 100 mg/kg dose of NNK and in 46% of these mice after a single 60 mg/kg dose of VC. In contrast, the tumor incidence in untreated C57BL/6 mice was 4%. Only one of 22 lung tumors from C57BL/6 mice treated with NNK contained an activated Ki-ras gene that was associated with an O6MG DNA adduct, whereas previous studies detected activated Ki-ras oncogenes in most of the NNK-induced lung tumors analyzed from susceptible A/J and resistant C3H mice. The small differences in formation and persistence of the O6MG adduct in whole lung or isolated lung cells from A/J and C57BL/6 strains do not account for the differences in either susceptibility for tumor formation or activation of the Ki-ras gene between these strains. In contrast to the low number of NNK-induced tumors with Ki-ras mutations in the resistant mice, 11 of 20 lung tumors from VC-treated mice contained activated Ki-ras genes. Neither p53 tumor suppressor gene mutations nor overexpression of the p53 protein were detected in spontaneous or chemically induced lung tumors in C57BL/6 mice. Thus, although Ki-ras activation was detected in some tumors, pathways independent of ras activation and p53 inactivation also appear to be involved in lung tumorigenesis in this resistant mouse strain. PMID- 8216737 TI - Ki-ras oncogene mutations in tumors and DNA adducts formed by benz[j]aceanthrylene and benzo[a]pyrene in the lungs of strain A/J mice. AB - Strain A/J mice received intraperitoneal injections of benz[j]aceanthrylene (B[j]A) or benzo[a]pyrene (B[a]P). At 24, 48, and 72 h, lung tissues were removed for analysis of B[a]P- or B[j]A-derived DNA adduct formation during the first 3 d of exposure. One group of mice exposed to these hydrocarbons was kept for 8 mo to determine lung tumor multiplicity, the occurrence of mutations in codons 12 and 61 of the Ki-ras gene in the tumors that arose, the relationship between Ki-ras oncogene mutations in tumors, and the presence and quantity of genomic DNA adducts. The major DNA adduct in the lungs of mice exposed to B[a]P was N2-(10 beta-[+B, 7 alpha, 9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene]yl) deoxyguanosine (BPDE-I-dGuo) arising from bay-region diolepoxide activation of B[a]P and was consistent with the occurrence of tumors with mutations GGT-->TGT (56%), GGT-->GTT (25%), and GGT-->GAT (19%) in codon 12, all involving mutations of a guanine. B[j]A, a demethylated analogue of 3-methylcholanthrene (3-MCA) with an unsaturated cyclopenta ring, produced 16-to 60-fold more tumors at equivalent doses than did B[a]P; the mutations in tumors were GGT-->TGT (4%), GGT-->GTT (30%), and GGT-->CGT (65%). Analysis of adduction patterns in DNA suggested that B[j]A was activated to form DNA-binding derivatives in A/J mouse lungs primarily at the cyclopenta ring even though B[j]A contains a bay region. As reported in the published literature, the mutation spectrum induced by 3-MCA in Ki-ras codon 12 of mouse cells is similar to that of B[a]P but not to that of its close relative B[j]A. In contrast to B[j]A, 3-MCA is activated mostly via a bay-region diol-epoxide since its cyclopenta ring is saturated and not easily epoxidates. Therefore, we propose that the GGT-->CGT mutations produced by B[j]A in Ki-ras codon 12 were mostly the result of cyclopenta-ring-derived adducts. PMID- 8216738 TI - Ki-ras mRNA regulation in untransformed mouse lung cells. AB - Although the Ki-ras gene is an often-observed transforming gene in lung tumors, little is understood of the factors that regulate the expression of the normal gene in lung cells. Therefore, we used untransformed mouse lung epithelial cells to determine the effect of serum, growth factors, and cell confluence on the regulation of Ki-ras mRNA expression. In subconfluent cells synchronized by 24-h serum deprivation, the refeeding of media containing serum resulted in the expression of both Ki-ras and H4 histone mRNA. No change in the expression of either gene was observed in cells refed with media alone. In confluent cell cultures, the refeeding of media with serum had no effect on the expression of these genes, suggesting that cell-density-dependent mechanisms can override the serum-induced stimuli for Ki-ras and H4 histone mRNA expression. Confluent cells expressed low but detectable Ki-ras mRNA levels consistent with constitutive expression of this gene independent of its role in mitogenic stimuli. EGF (10 ng/mL) and TGF-alpha (10 ng/mL) were found to induce transient increases in Ki ras mRNA but large increases in H4 histone mRNA levels. Similarly, 48-h conditioned media obtained from two transformed mouse lung cells containing activated Ki-ras genes and overexpressing Ki-ras mRNA were observed to increase both Ki-ras and H4 histone mRNA in the untransformed mouse lung cells. The expression of these genes in mouse lung cells therefore appeared to be linked to stimuli provided by specific growth factors as well as by autocrine factors elaborated by lung tumor cells. The studies reported here provide insight into the regulation of the Ki-ras mRNA in untransformed lung cells and the factors that may contribute to the elevated levels of Ki-ras mRNA often observed in transformed lung cells. PMID- 8216739 TI - ras mutations in 2-amino-3-methylimidazo-[4,5-f]quinoline-induced tumors in the CDF1 mouse. AB - 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is a very potent mutagen that is carcinogenic in rodents and nonhuman primates. IQ-induced CDF1 mouse lung and liver tumors were examined for activated Ki-ras and Ha-ras genes, respectively. Polymerase chain reaction (PCR)-amplified target DNAs were analyzed for mutations of codons 12, 13, and 61 by single-strand conformation polymorphism (SSCP) and direct sequencing methods. All mutations were localized to codon 61 of the ras genes. Forty-nine of 54 lung tumors induced by IQ possessed activating Ki-ras mutations, as did 20 of 26 lung tumors from the vehicle-treated animals; 80% and 75% of these mutations, respectively, were A-->T transversions of the second nucleotide redundant. One lung adenoma from the IQ-treated group contained a tandem duplication of the sequence corresponding to codons 50-57 of the Ki-ras gene (unpublished observations). In addition, seven of 34 IQ-induced liver tumors harbored activating Ha-ras mutations: five were C-->A (G-->T) transversions at the first nucleotide, and two were A-->T transversions at the second nucleotide of codon 61. None of the 15 liver tumors collected from the vehicle-treated mice possessed Ha-ras mutations in codon 12, 13, or 61. These data indicate that IQ induces Ha-ras gene activation in CDF1 mouse liver tumors. The mechanisms of lung tumor induction by IQ, however, is obscured by the high frequency of Ki-ras A-->T mutations observed in both the IQ-induced and spontaneous lung tumors. The different ras mutational spectra in lung and liver tumors may suggest either that two different pathways of IQ metabolism exist in these organs or that IQ contributes to CDF1 lung tumorigenesis by a mechanism other than its direct interaction with the Ki-ras gene. PMID- 8216740 TI - Yuanhuacin A is a selective antagonist of phorbol ester receptor in protein kinase C. AB - Protein kinase C with a molecular weight of 82 kD has been purified to electrophoresis homogeneous from rat brain through a series of chromatography columns including DE-52, Sepharose G-200 and phenyl-Sepharose. The enzyme possessed autophosphorylation activity. Yuanhuacin A inhibited the 3H-phorbol-12, 13-dibutyrate (3H-PdBu) binding of PKC with an IC50 value of 1.48 +/- 0.28 x 10( 8) mol/L when the concentration of 3H-PdBu was 1.5 x 10(-9) mol/L (Ki = 1.2 x 10( 8) mol/L). Yuanhuacin A inhibited the PdBu-stimulated PKC activity in the catalysis of the phosphorylation of Histone III-S with an IC50 of 2.82 +/- 0.37 x 10(-9) mol/L (PdBu = 10(-6) mol/L), while it had no effect on the basal and Ca(2+)-stimulated PKC activity in the same assay system. This result suggests that Yuanhuacin A is a selective antagonist of the phorbol ester receptor in protein kinase C. PMID- 8216741 TI - Possibility of targeting treatment for ischemic heart disease with liposome (II). AB - Studies on the isolated rat heart perfusion model have proved that perfusion with high Ca2+ (4.5 mmol/L), high K+ (8.7 mmol/L) or free radical generating system (FRGS) significantly increases myocardial uptake of liposomes. Intravenous injection of liposomes covalently combined with antibody of rat myocardial cells obviously elevates the target action of liposomes to myocardium. Liposome-carried SOD for treatment of rat myocardial ischemia-reperfusion injury is much more effective than simple SOD. The results evidence that the liposome as drug carrier for treatment of ischemic heart diseases shows a broad prospect for its clinical use. PMID- 8216742 TI - The antagonistic effect of cholecystokinin octapeptide (CCK-8) on opioid effects in cardiovascular activities was mediated by CCK-B receptor. AB - Previous studies have shown that CCK-8 has distinct antiopioid effect in the central sites related with pain control and blood pressure control. The aim of this study was to explore the receptor mechanism by which CCK-8 antagonized the depressor effect of u- and k-opioid agonists, and to observe whether CCK-8 could antagonize the depressor effect induced by muscimol, a nonopioid substance. The results showed that (i) The antagonistic effect of CCK-8 on opioid-induced hypotension could be blocked by intrathecal (i. t.) administration of CCK-B antagonist L-365, 260 at nanogram doses, or by CCK-A antagonist devazepide at doses 20-40 times higher than L-365, 260, indicating that it was the CCK-B receptor which mediates the antiopioid effect. (ii) The depressor effect induced by intrathecal muscimol, a GABA agonist, was blocked neither by naloxone nor by CCK-8, supporting the notion that CCK-8 is an endogenous opioid antagonist rather than a universal anti-hypotension agent. PMID- 8216743 TI - Inhibitory effect of anisodamine on the neuropathic hyperalgesia following peripheral nerve injury (II). AB - A peripheral neuropathy with hyperalgesia and allodynia was produced by loosely tying constrictive ligature around the left sciatic nerve of rats, i.v. injection of anisodamine 20 mg/Kg abolished both neuropathic hyperalgesia responses to noxious radiant heat and ectopic discharges generated from the injured region of the nerve. Anisodanime applied either systemically or locally to the damaged area of the nerve not only ceased the spontaneous ectopic discharges recorded from A beta to C fibers but also blocked the afferent ectopic discharge elicited by K+ channel blocker, noradrenaline, Ca2+ or antidromic stimulation of sciatic nerve proximal to the injured nerve area. The experiments indicated that anisodamine probably possessed a calcium channel blocker-like activity and produced selective block of the new channels in the injured area. It is suggested that anisodamine may be a candidate therapeutic agent in relieving hyperalgesia and allodynia following nerve injury. PMID- 8216744 TI - A reevaluation of the critical membrane potential of the effective refractory period in guinea pig ventricular fibres. AB - The traditional critical membrane potential (CMP), -55(-)-60 mV, which corresponds to effective refractory period (ERP), was anew investigated in guinea pig ventricular muscle fibres. The electrical and contractile responses to the stimulus during repolarization of action potential (AP), particularly from +10 to -60 mV, were observed. One third of 35 tested cells displayed testing action potential (TAP) and local response at > or = -54 mV when they were stimulated by testing pulses in 37 degrees C normal Tyrode's solution. Potential level of TAP which occurred earliest was at -30 mV and that of local response which appeared earliest was at 0 mV during repolarization among 95 systematic tests. Most of the TAPs belonged to the slow response potential type. The ratio of TAP evoked at > or = -54 mV initial membrane potential (IMP) was as high as 86% when the experiment was carried out in 37 degrees C 1.5 mmol KC1/L Tyrode's solution. In view of distribution of IMPs of TAPs, the CMP of ERP in guinea pig ventricular muscle fibres was more positive than traditional CMP measured by Hoffman et al. in dog, sheep Purkinje fibres and had a quite changeable range. The CMP of every cell in ventricular muscle was not all the same, and their CMPs approximated to normal distribution. There was no sharp line separating ERP from relative refractory period in myocardium. Higher temperature and low [K]0 were the important factors elevating CMP of ERP. PMID- 8216745 TI - Interaction between HMG proteins (1 + 2) and the negative regulatory region 1 (NCR1) in the 5'-flanking sequence of the human beta-globin gene. AB - The pattern of high mobility group proteins 1 and 2 (HMG1,2) interaction with the 5'-flanking sequence of the human beta-globin gene has been analyzed by scanning tunnelling microscopy (STM). A 200 bp negative regulatory region in the 5' flanking sequence of the human beta-globin gene can be folded by HMG proteins 1 and 2 into a circular structure (diameter 70 +/- 6 A) with a linear tail which seems to be a left-handed double helix structure. PMID- 8216746 TI - Effect of endothelin, angiotensin II and ANP on proliferation of vascular smooth muscle cells and cardiomyocytes. AB - By means of cell culture, 3H-thymidine (3H-TdR) incorporation and c-fos oncogene dot plotting technique, it was found that endothelin (ET) and angiotensin (ANG II) could promote proliferation and DNA synthesis of cultured vascular smooth muscle cells (VSMCs) and myocardial cells, and stimulate expression of c-fos oncogene of VSMCs. However, atrial natriuretic peptide (ANP) antagonizes the above effects of ET and ANG II. PMID- 8216747 TI - [Renin-angiotensin system of the uterus and ovary in mammalian females]. AB - The circulating reninangiotensin system (RAS) participates in the regulation of blood pressure and electrolyte metabolism. Renin, a proteolytic enzyme, synthesized in the kidney from its biological precursor, prorenin, cleaves its substrate angiotensinogen in the blood to form the active octapeptide, angiotensin II (AII). All the RAS components are present in the reproductive system of mammals. During pregnancy, the level of prorenin increases in the plasma. The ovary is the source of this prorenin during early pregnancy and maternal decidua later on. During the menstrual cycle, the thecal of preovulatory follicles synthesize prorenin, renin and AII. Thecal renin synthesis is controlled by LH/hCG as demonstrated in vivo and in vitro in the rabbit. Ovarian renin seems to be identical to kidney renin. Prorenin appears to be the major secretory product rather than renin, which remains intracellular. AT2-type angiotensin II-receptors are expressed in the rat on follicular granulosa cells and could be down-regulated by FSH. The bovine thecal cells also express AT2 receptors, up-regulated by LH. These data are consistent with an autrocrine or paracrine role for ovarian RAS. It has been implicated in neovascularization of the follicle and regulation of steroidogenesis by increasing the androgen/estrogen ratio, an index of follicular atresia. PMID- 8216748 TI - Post-prandial lipase, pepsin and acid secretion of a Heidenhain pouch in the rabbit. AB - The kinetics of the gastric secretion of lipase, pepsin and acid were studied after a meal in Heidenhain-pouch rabbits. After a 24-h fast, feeding immediately stimulated (< 15 min) lipase (x 4.1) and later on pepsin (x 1.8) output which reached respectively 16 and 47% of the output observed after pentagastrin stimulation (64 micrograms.kg-1.h-1 for 1 h), and which were significantly correlated. Lipase concentration was enhanced earlier and to a greater degree (x 7.3) than pepsin concentration (x 2.5). No stimulation of high basal acid secretion occurred. It was concluded that: 1) gastric lipase secretion is stimulated by feeding in the rabbit; 2) pepsin secretion is stimulated by feeding. The modalities of the secretion of lipase and pepsin are compatible with the existence of distinct secretory cells; 3) acid secretion is not stimulated by feeding. The decrease in acid secretion during the post-prandial phase favors a physiological role for lipase which is altered by low pH. The absence of acid stimulation by feeding in the rabbit, in contrast to other species, requires additional studies on the release of gastrointestinal hormones, namely gastrin, cholecystokinin and somatostatin. PMID- 8216749 TI - Influence of moderate food restriction on calcium metabolism in pregnant rats. AB - Two groups of female rats, non-pregnant (NP) and pregnant (P1), were fed ad libitum. A second group of pregnant rats (restricted diet, P2) were restricted for 14 d to the same intake as NP, and their ration was then increased by 5% from d 14 to d 21. For the first 3 d P1 and P2 absorbed a higher percentage of calcium than NP. During the final wk of pregnancy serum calcium decreased and 1,25 dihydroxycholecalciferol increased regardless of the dietary regimen. In both P1 and P2, femur calcium was higher than in NP on d 7 and apparent bone density increased during the 2nd wk of pregnancy and decreased from then on, this decrease being more pronounced in P2. On d 21, P2 fetuses were smaller and contained a smaller amount of calcium than those in P1, although the calcium concentration in the body remained similar in both groups of fetuses. PMID- 8216750 TI - [Influence of dietary calcium/phosphorus ratio on blood calcium, phosphate and magnesium during gestation in the rabbit]. AB - Sixteen Thies strain rabbits were used to study the effect of the calcium/phosphorus ratio on plasma calcium, inorganic phosphorus and magnesium levels during pregnancy. Animals were allocated in 2 groups of 8: one receiving a diet with a Ca/P ratio of 1:0 and the other a diet with Ca/P ratio of 2:1. Water was given ad libitum for all rabbits. Results obtained showed that Ca blood level was significantly higher in rabbits receiving the diet with Ca/P ratio of 2:1 before covering and during the first week of pregnancy. During the last 15 d of pregnancy, Ca blood level decreased significantly in the 2 groups of animals. Plasma inorganic phosphorus and magnesium levels were not significantly different in the 2 groups of rabbits until the 2nd wk of pregnancy. But at the end of pregnancy, while phosphatemia and magnesemia decreased in rabbits fed a high Ca/P ratio, in the other group these parameters remained unchanged. PMID- 8216751 TI - Effect of recipient doe genotype on survival rate at birth of frozen rabbit embryos. AB - The effect of the genotype of 2 selected rabbit strains (White New Zealand and Synthetic) on the survival rate at birth of frozen embryos was studied. Morulae were obtained 64-66 h postcoitum from 32 multiparous does naturally mated with males of the same strain (16 does of Synthetic strain (SY) and 16 does of the White New Zealand strain (NZ)). Morphologically normal morulae were slowly frozen in 1.5 M DMSO and stored in liquid nitrogen. After thawing, intact embryos from both strains were transferred into the oviducts of 32 recipient does of both strains (16 SY strain does and 16 NZ does). Significant differences were observed in pregnancy rate and survival rate at birth between strains of recipient does. The recipient does of the SY strain showed a higher pregnancy rate than those of the NZ strain (87.5% versus 25% respectively; P < 0.05). When the survival rate at birth was analyzed in all recipient does, this was found to be 28 +/- 4% in SY recipient does versus 8 +/- 4% in NZ recipient does (P < 0.01). However, when the survival rate was analyzed in pregnant recipient does, no significant differences were found between embryo strains and recipient strains, the average survival rate was approximately 32%. The major factor in the differential survival rate between SY and NZ embryos was due to the genotype of recipient does. PMID- 8216752 TI - [Relation between food intake and oxygen consumption of organs drained by the portal vein in the conscious pig]. AB - The intestinal absorption of glucose and alpha-amino nitrogen, the appearance of D-and L-lactic acids in the protal vein and the consumption of oxygen by the organs of the abdominal extrahepatic splanchnic area were studied simultaneously in pigs either during the postprandial period or during a fasting period of the same length. For this purpose, 5 growing pigs (59.4 +/- 3.5 kg live weight) were fitted with permanent catheters in the portal vein and carotid artery and with an electro-magnetic flowmeter probe around the portal vein. This device was used to measure the exchanges between the blood and the intestinal lumen. For a period of 1 wk, the animal received a semi-synthetic diet containing 6% purified cellulose (R6) and then during the next wk, a diet containing 16% purified cellulose (R16), the order of distribution being alternated from one animal to the next. During each of these 2 wk and after a fasting period of 16 h, they were subjected to 2 successive tests of 5 h, either after intake of an 800-g meal (R) (R6 or R16), or after no meal intake (J6 or J16). During these tests, blood samplings were made at 15 to 30-min intervals, the consumption of oxygen was recorded by an ABL3 radiometer and the afore mentioned nutrients and metabolites analysed in these samples. The consumption of oxygen was higher (P > 0.01) during the postprandial period (5.41 +/- 0.19 mmol/kg/h) than during the fasting period (4.64 +/- 0.19 mmol/kg/h) while the availability of oxygen only increased slightly (P < 0.05) (14.01 +/- 0.66 vs 13.08 +/- 0.76 mmol/kg/h). By contrast, the oxygen extraction coefficient did not significantly increase with meal intake. The appearance of L lactic acid in the portal blood was higher (P < 0.001) during the postprandial period (3.83 +/- 0.32 g/h) than during the fasting period (1.23 +/- 0.23 g/h). The energy expenditure due to the aerobic metabolism of the organs drained by the portal vein ranged from 35.7 to 37.8 kcal/h after meal intake, ie 1-18% more than after fasting. The anaerobic metabolism only represented 0.3-0.4% (fasting) and 1.1-1.3% (postprandial period) of this aerobic metabolism. Oxygen consumption was not changed by the dietary cellulose content. PMID- 8216753 TI - Ram-induced short luteal phases: effects of hysterectomy and cellular composition of the corpus luteum. AB - Two experiments were conducted on Prealpes ewes to test 2 complementary hypotheses which may explain the short lifespan of corpora lutea observed in some cases after ram-induced ovulation: i) the possible role of the uterus was tested by determining the effects of hysterectomy on the duration of luteal phases after the ram effect (RE); ii) the possible difference due to characteristics of follicles before ovulation was tested by determining the cellular composition and characteristics of corpora lutea (CL) induced by the RE compared to CL of the breeding season (BS) when ovulation is synchronized by FGA-impregnated sponges. In the first experiment, 9 ewes were hysterectomized (Hys) and introduced to rams at the same time as 10 control ewes. Plasma progesterone (P4) was analyzed each day for 17 consecutive d after the introduction of rams. The number of females ovulating was not different for the 2 groups (7/9 vs 9/10, respectively), but no Hys ewes experienced short cycles compared to 5 of the 9 control ewes (P = 0.029). The second experiment involved 16 ewes subjected to the RE in June, and 5 cyclic ewes in January. The ewes were ovariectomized 82 h after the preovulatory LH surge, the CL were separated, weighted and the luteal cells enzymatically dissociated to count the relative proportions of small (< 20 mu diameter) and large cells and assess in vitro P4 secretion both with and without stimulation with 100 ng ovine LH. Plasma P4 concentration increased significantly more slowly in RE than in BS eves (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216754 TI - Serum total cholesterol, high-density lipoprotein-cholesterol and triglyceride concentrations in lambs following supplementation with various forms of tocopherol. AB - A 61-d study involving 40 crossbred lambs evaluated the effect of various forms of tocopherol provided daily in equimolar amounts on total cholesterol, high density lipoprotein-cholesterol and triglyceride concentrations in the serum of lambs. Thirty-five lambs were allotted to 7 treatment groups of 5 animals each, supplemented with 300 mg tocopherol either as: 1) DL-alpha-tocopheryl acetate; 2) D-alpha-tocopheryl acetate; 3) D-alpha-tocopheryl succinate; 4) D-alpha tocopheryl polyethylene glycol 1,000 succinate (TPGS); 5) DL-alpha-tocopheryl nicotinate; 6) DL-alpha-tocopheryl nicotinate (150 mg) + 150 mg TPGS; and 7-D alpha-tocopheryl acetate (150 mg) + 150 mg TPGS mixed with the commercial flock diet. In addition, another group of 5 lambs were used as control (no vitamin E supplementation). Dietary supplementation of various vitamin E sources resulted in no overall treatment effects for total cholesterol, triglycerides or high density lipoprotein-cholesterol. A significant variation was noticed among animals. The levels of all measured serum components varied throughout the experimental period (P < 0.0001). The day x treatment interaction was not significant (P > 0.05) for any serum measured component. The present data strongly suggest that short-term treatment (< 2 mo) with pharmacological oral doses of various forms of vitamin E did not influence serum lipid metabolism of lambs. The data also showed that the bioavailability of alpha-tocopherol is dependent on the form administered. D-alpha-tocopherol acetate is a highly available form, the bioavailability of which is further increased when combined with D-alpha-tocopheryl polyethylene glycol succinate. PMID- 8216755 TI - Peripheral concentrations of a 60-kDa pregnancy serum protein during gestation and after calving and in relationship to embryonic mortality in cattle. AB - In order to have a specific marker for studying pregnancy in cattle we examined the characteristics of a pregnancy serum protein produced by the placenta (PSP60). Its profile in peripheral blood was determined by radioimmunoassay in pregnant cows of 3 breeds after artificial insemination (AI): Charolais (n = 24), Normande (n = 24) and Holstein (n = 26). From 27 d post-AI to the end of pregnancy the plasma PSP60 concentration increased, especially during the last 2 wk, to reach a peak a few d before calving, which was higher (P < 0.001) in the Charolais (1,238 +/- 422 ng/ml) than in the other breeds (528 +/- 458 and 444 +/- 204 ng/ml). With an apparent half-life of approximately 8 d, this protein was still detectable in the maternal blood from 105, 85 and 87 d post-partum in the Charolais, Normande and Holstein breeds, respectively. Fertility results on 1,102 inseminations in the Charolais breed showed that the PSP60 concentration dropped then disappeared after embryonic mortality. Sequential assays of this protein between 28-90 d after AI are useful for studying the course of pregnancy, although they do not allow discrimination between early embryonic mortality and non-fertilization which together constitute 75% of pregnancy failures. PMID- 8216756 TI - Interactions between proteolytic and cellulolytic rumen bacteria during hydrolysis of plant cell wall protein. AB - During the degradation of the plant cell wall protein of dried alfalfa, interactions may occur between hydrolytic activities of cellulolytic (Ruminococcus albus or Fibrobacter succinogenes) and proteolytic (Prevotella ruminicola or Butyrivibrio fibrisolvens) bacteria. In vitro the hydrolysis of these protein compounds begins after the depolymerization of the cell wall polysaccharides has started. Maximal degradation of cell wall protein of dried alfalfa (37.2%) was obtained with cocultures of Prevotella ruminicola and Ruminococcus albus. PMID- 8216757 TI - Evaluation of the relationship between social status and reproductive performance in farmed blue foxes. AB - An experimental cage system was designed for evaluating the association of social status and reproductive performance in blue foxes under fur-farm conditions. The present test cage apparatus consisted of 6 small cages and 1 large cage that were connected. The small cages were utilized for males of different social status and the large cage for females coming on heat. The results showed that this type of testing apparatus can be used for evaluating a female's acceptance of males of different social rank. The locomotor activity of males significantly depended on their social status; thus the most active individuals in the test were the most dominant, and vice versa. Females most often accepted higher-ranking males. Juvenile males were the least dominant and also the least accepted by females. Urination activity was not necessarily related to dominance. PMID- 8216758 TI - Amino acid concentrations in cerebrospinal fluid and serum in Alzheimer's disease and vascular dementia. AB - Cerebrospinal fluid (CSF) and serum levels of 22 amino acids were studied in 13 patients with dementia of the Alzheimer type (DAT), 13 patients with vascular dementia (VD) and 15 age-matched controls. We found significantly reduced levels of glutamate in CSF samples from DAT patients compared to VD and control subjects, but CSF levels of aspartate were found to be significantly elevated in the two groups of dementia studied. Moreover, CSF concentrations of tyrosine, leucine and phenylalanine were significantly increased in VD patients in comparison with those in DAT patients and control subjects. Our results showed a wide increase in CSF/serum amino acid ratios in DAT and VD groups compared to controls. However, no differences were found in CSF/serum ratios between dementia groups. These changes show evidence for a possible disorder of amino acid metabolism with different patterns in these two dementia types. PMID- 8216759 TI - Disturbance of colour perception in Parkinson's disease. AB - A computer-aided method for the determination of colour fusion time (CFT) was developed. CFT indicates the acuity of the perception of monochromatic contours. CFT was determined in 36 patients with Parkinson's disease (PD) and compared with a group of 36 age- and sex-matched controls. Patients with PD generally had a shortened fusion time, especially for dark-green, light-blue and dark-red stimuli. The results give evidence to the hypothesis of a colour perception disorder in PD. The physiological and pathoanatomical basis of this phenomenon is unknown, but a functional deficit of cortical neurons may be a probable cause. PMID- 8216760 TI - Attenuation of haloperidol-induced catalepsy by noradrenaline and L-threo-DOPS. AB - In addition to impaired dopaminergic neurotransmission a dysfunctional noradrenergic system has been demonstrated in Parkinson's disease. L-threo-3,4 dihydroxyphenylserine (DOPS), a synthetic precursor of noradrenaline (NA), appears to be effective in the treatment of some akinetic symptoms in parkinsonian patients. In the present study the possible effect of DOPS was studied in rats, in which catalepsy was induced with haloperidol as a model for parkinsonian akinesia. Intravenous infusion of NA (1.5 and 15 micrograms/kg) or DOPS (2 and 4 mg/kg) in male Wistar rats (240-290 g) significantly decreased catalepsy. The effect of DOPS was abolished by pretreatment with the peripheral decarboxylase inhibitor benserazide (2 mg/kg). Pretreatment with Ro 40-7592, a catechol-O-methyltransferase inhibitor, potentiated and prolonged the anticataleptic effect of DOPS. The findings suggest a peripheral site of NA mediated anticataleptic action. Therapy with DOPS may be successful only without a peripheral decarboxylase inhibitor. Moreover, the therapeutic effect of DOPS may be potentiated by COMT inhibition. PMID- 8216761 TI - Effect of phosphatidylserine on free radical susceptibility in human diploid fibroblasts. AB - We studied the effect of phosphatidylserine (PdtSER) on oxygen metabolite toxicity in skin fibroblast cell lines from apparently normal subjects. Fibroblast damage was produced by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by xanthine-oxidase (Xo). In order to quantify cell damage, we measured lactate dehydrogenase (LDH) activity in culture medium and cell viability in fibroblast cultures, with and without preincubation for 4 days with PdtSER 13 microM, after Xo incubation. We found a significant increase of LDH activity in culture medium of cells without preincubation with PdtSER. No significant increase of LDH activity was observed in the same cell lines after preincubation with PdtSER. PMID- 8216762 TI - Childhood thermal injuries in New Zealand resulting in death and hospitalization. AB - Thermal injury is a significant contributor to the overall problem of injury among children. Children are at greater risk of hospitalization due to thermal injury than any other age group, and their fatality rate is second only to those over 60 years of age. This study provides an overview of thermal injury in New Zealand children, age 0-14 years, resulting in death or hospitalization. Eighty one thermal fatalities were identified from Health Statistical Services (HSS), Department of Health, data accessed for the 10-year period from 1978 to 1987. The records of the Coroners' Court, held by the Justice Department, were also accessed in order to gather additional information about the circumstances of fatal injury in each case. Thermal injury hospital admissions (n = 634) were identified from HSS data for the year 1988. Children were more likely to die in house fires than any other thermal injury event. Most house fires were started by smoking paraphernalia or electrical appliances. Two-thirds of the childhood thermal injury hospitalizations were due to contact with hot water, the most commonly identified source being a hot beverage. Thermal injury rates for New Zealand children are higher than reported overseas. Prevention strategies that have proven effective elsewhere are discussed with recommendations for New Zealand. PMID- 8216763 TI - Myocardial [3H]polyinositol phosphates and their response to burn trauma. AB - Polyinositol phosphates comprise a portion of the phosphatidyl signal transducing system. The most well known is IP3 which stimulates Ca2+ release from Ca2+ sequestering organelles within cells. In this study, polyinositol phosphate changes in the heart subjected to the systemic effects of burn trauma were examined. The hypothesis was that systemic trauma induced by large body surface area (% BSA) burn may perturb the phosphatidylinositol signal transducing system. At postburn day 21 left ventricular tissues were harvested from mice with varying burn sizes (i.e. 0, 20 and 50 per cent). Levels of the polyinositol phosphates were measured by incorporation of myo-[2-3H]inositol with separation of the phosphates by anion-exchange chromatography. Analysis of variance was used for statistical evaluation. Multivariate relationships between the independent polyinositol forms (inositol, Il,4P2 and I1P) existed for control (r2 = 0.71 and 50 per cent burn groups (r2 = 0.78). Numerous interdependent relationships existed within each of the multivariate tests. These analyses confirm that several independent polyinositol phosphates contribute to changes in the second messenger IP3 in ventricular tissue subjected to the systemic effects of burn trauma. Disruption of the polyinositol phosphates may underlie either the cause, or exacerbation, of heart dysfunction and cellular damage in burn patients. PMID- 8216764 TI - Case-fatality rates by body part affected and trends in hospitalized burns in Maryland, 1981-90. AB - This study was undertaken (i) to determine in-hospital case-fatality rates (CFRs) by severity using body part(s) affected as a proxy, and (ii) to examine the trends in hospitalized burns regarding CFRs. The study used the Health Service Cost Review Commission non-confidential Maryland hospital discharge data for the years 1981-90. CFRs were computed as percentages of hospitalized burns that died. Chi-square tests were used to assess homogeneity for categorical variables and to examine linear trends. The CFR for hospitalized burns was 2.9 per cent. CFR was highest among the elderly (13.1 per cent) and for burns affecting multiple specified sites (7.4 per cent), and lowest among children (1.1 per cent) and for upper limb burns (0.22 per cent). Burn CFR increased overall by 59 per cent for 1981-90, with a decreasing rate only in children. However, after controlling for age and degree of burn no significant change in trend in CFRs over the 10-year period was evident. The findings demonstrate that while child burn fatality seems to have declined, the elderly continue to have high CFR for burns regardless of the body part affected, and that the CFRs for hospitalized burns remained constant between 1981 and 1990 in Maryland despite considerable advances in treatment. PMID- 8216765 TI - Efficacy of a broad-spectrum antibiotic (mupirocin) in an in vitro model of infected skin. AB - The microbicidal effect of mupirocin (Bactroban) was studied using an in vitro model of burn eschar in contact with this antimicrobial cream, to indicate its inhibiting action after 1, 2, 4, and 24 h. The microorganisms used were 20 isolates of Ps. aeruginosa, 20 isolates of MRSA, 10 isolates of Staph. epidermidis, 12 isolates of Enterobacteriaceae and eight isolates of Candida albicans. There was a marked effect on Gram-negative bacilli (< 0.1 per cent surviving) by 4 h, whereas on Gram-positive organisms its effect was slower, principally on MRSA with 2.2 per cent survivors by 24 h. The action on Candida was very slow initially, but after 24 h, the mupirocin's effect was marked (< 0.1 per cent survivors). The studies showed that mupirocin (a topical broad-spectrum antimicrobial agent) can be used in vitro against Gram-positive and Gram-negative bacteria and yeasts, which contaminate skin and mucosa. Further clinical experience is required before mupirocin can be used to treat colonized or infected wounds in burned patients. PMID- 8216766 TI - Exosurf treatment following wood smoke inhalation. AB - Pulmonary surfactant deactivation is an important factor in the pathophysiology caused by wood smoke inhalation. Surfactant replacement is beneficial in treatment of surfactant-deficient neonates and possibly the adult respiratory distress syndrome (ARDS). In this study, the effect of exogenous Exosurf treatment for acute wood smoke injury was examined in four groups of rabbits. All groups were anaesthetized, placed on a ventilator, and surgically prepared for haemodynamic, peak airway pressure (P(aw)), and blood gas measurements. Rabbits were monitored for 2 h following smoke or sham smoke inhalation. At the conclusion of the experiment pulmonary oedema and surfactant function were measured. A Control group (n = 5) was followed without intervention. A Smoke group (n = 4) was ventilated with wood smoke for 3 min. A third group (Smoke+Exo, n = 4) was subjected to smoke followed by pulmonary instillation of Exosurf (5 ml/kg). Saline (5 ml/kg) was instilled into the lungs of the fourth group (n = 3) as a control for Exosurf instillation. Saline, Smoke and Smoke+Exo all significantly lowered PO2 and elevated P(aw) compared to baseline and the Control group. Exosurf treatment did not reduce the pulmonary oedema or restore surfactant function caused by smoke exposure. This study indicates that wood smoke inhalation acutely damages the lung and that administration of Exosurf by instillation is not an effective treatment. PMID- 8216767 TI - Quantitation of cytokine levels in skin graft donor site wound fluid. AB - We quantified endogenous levels of multiple cytokines in skin graft donor site wounds in patients with small to moderate-sized burn injuries. Thirteen patients aged 11 months to 61 years with mean TBSA burn of 4 +/- 1 per cent underwent placement of occlusive wound dressings on partial skin thickness donor site wounds. Fluid was aspirated from beneath the dressing on postoperative day 1 and every subsequent 24 h until no further fluid could be obtained. Interleukin-1 alpha (IL-1) and tumour necrosis factor-alpha (TNF-alpha) levels were determined by enzyme-linked immunosorbent assay (ELISA). Epidermal growth factor (EGF), basic-fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) were measured by an enzyme immunoassay (EIA). We found substantial levels of EGF and TNF-alpha in the donor site wound fluid in all 13 patients; detectable levels of bFGF in five patients; and elevated levels of IL-1 in three patients. There were no detectable levels of these cytokines in normal human serum. In contrast, there were no measurable levels of PDGF in any patient's wound fluid; the mean level in serum was 1.5 ng/ml +/- 0.2 s.e.m. Studies of cytokines in the normal wound healing environment may help in the design of future therapies to augment wound healing. PMID- 8216768 TI - Cryopreservation of cultured dermal fibroblast impregnated collagen gels. AB - The survival of cultured dermal fibroblasts was evaluated following manufacture, freezing and disaggregation of fibroblast-impregnated collagen gels. The concentration which gave optimal cell survival was determined for three cryoprotectants (glycerol, dimethyl, sulphoxide (DMSO) and ethanediol) and their efficacy compared. DMSO led to the highest cell viability after freezing and thawing. The effect of rate of freezing was also compared and 0.5 degree C/min (within the range 20 degrees C to -70 degrees C) was found to result in a significant enhancement of cell viability in comparison with freezing at 1.0 degree C/min or rapid freezing. PMID- 8216769 TI - An approach to the management of toxic epidermal necrolysis in a burn centre. AB - Toxic epidermal necrolysis syndrome, a life-threatening skin disorder, requires specialized nursing care to optimize survival. The similarity of the condition to partial skin thickness burns suggests that management on a burn unit is an effective means of therapy. A review of eight patients treated at our Burn Center emphasizes the need for aggressive team management of the condition. PMID- 8216770 TI - Scalds related to bleeding domestic heating radiators. AB - While scalds are the commonest burns within the home, scalds resulting from bleeding domestic central heating radiators have not previously been reported. We have encountered two examples of significant burns to the hands received in this way. The incidence of these injuries in the UK is unknown but several similar cases have been identified by the Consumer Safety Unit of the Department of Trade and Industry. The mechanism of injury is described and recommendations made for safely bleeding domestic central heating radiators. PMID- 8216771 TI - Paediatric burns in central Finland between the 1960s and the 1980s. AB - This study comprised 359 paediatric burn-injury cases. The patients were collected from the 1960s, 1970s and 1980s, taking 4 years from each decade. These children were treated exclusively in the Paediatric Surgery Department in the University Hospital of Tampere, Finland. We were interested in the backgrounds and living environments of our patients as well as the children themselves. Special attention was paid to risk factors and methods for prevention. Scalds at home and in the sauna rooms constituted the largest groups of injuries. The number of hospitalized patients has slightly decreased during the past three decades, whereas the proportion of girls has increased. The mortality was very low (0.28 per cent), a single case. This study shows that 80 per cent of born injuries in children occurred under the age of 4 years and over 80 per cent of all burn injuries involved hot liquids; modern kitchen technology has not significantly reduced this factor. The epidemiological profile of paediatric burns changed from the 1960s to the 1980s less than expected. PMID- 8216772 TI - Long-term gastrointestinal problems in burns patients. AB - Paralytic ileus occurs commonly in patients with over 20 per cent TBSA burns in the first few days after the burn. In the absence of sepsis, it is unusual for abdominal problems to develop later. We present an example of acute abdominal pseudo-obstruction occurring 5 weeks after a burn and review the management of this condition. PMID- 8216773 TI - Assault inflicted by hot water. AB - Assault inflicted by hot water is uncommon although such injuries have been reported from many parts of the world. The patient characteristics, burn distribution and outcome in 127 patients who had been intentionally assaulted with hot water during a 7 1/2 year period are reported. More than half of the males were assaulted by their wives. The female was often assaulted by her spouse or another family member. Most patients came from lower socioeconomic groups. The average burn surface area was 13.7 per cent (range 1-45 per cent). The upper part of the body was much more frequently burned than the pelvic and lower limb areas (12 per cent). Males (94) were assaulted more commonly than females (33). Eighty four patients suffered partial skin thickness burns requiring debridement and skin grafting. The average hospital stay was 17 days (range 1-61 days). Upper body hot water burns in adults should raise the possibility of assault in the minds of attending medical personnel, especially where predisposing factors exist (alcohol abuse, lower socioeconomic strata, poor education). Most patients sustain partial skin thickness burns and will require debridement and grafting. Psychosocial factors require investigation and professional intervention. PMID- 8216774 TI - Reconstructive management of patients with greater than 80 per cent TBSA burns. AB - With improving acute burn care, greater numbers of patients are surviving large burns. Meshed skin grafts or cultured epithelial autografts are often required to achieve rapid wound closure, even in areas such as the hands or face. This, plus the lack of suitable donor tissue for reconstruction, is mandating a change in reconstructive principles. Twenty-eight patients surviving > or = 80 per cent TBSA full skin thickness burns were evaluated using two specially devised instruments (Inventory of Potential Reconstructive Needs; Donor Tissue Surveillance). A total of 564 reconstructive needs were identified in the 28 patients, an average of 20.1 per patient. There were 265 defects in the head and neck, 143 in the upper extremities, and 156 in the torso/lower extremities. The injured anatomical units most frequently identified were the hand (74), trunk (60), nose/nasolabial fold (48), mouth (46), ankle/foot (42), neck (31) and check (28). The Donor Tissue Surveillance form revealed that the necessary donor tissue was frequently not available, and when available, was often of poor quality. These facts require a different set of priorities for reconstruction of the massively burned patient. No longer can a simple stepwise plan of active function, passive function, and aesthetic needs be followed. The patient and family desires must be combined with a realistic outlook by the entire burn team to determine the most judicious and efficient use of available donor tissue to meet the reconstructive needs. PMID- 8216775 TI - Experience with polymicrobial sepsis in a regional burn unit. AB - A 2-year review of 795 patients admitted to a regional burn unit was carried out to determine the incidence of polymicrobial sepsis. Of 38 bacteraemic patients, 21 (55 per cent) had polymicrobial sepsis in 1990. Of 38 cases in 1991, 12 patients (31.6 per cent) had polymicrobic infections. Of 36 deaths in 1990, 13 were attributed to sepsis, 12 of 29 (31.6 per cent) in 1991. Of the patients who died in 1990, eight (21 per cent) were polymicrobic septic deaths and six (15.8 per cent) in 1991. The problem has been reported in immunocompromised patients, especially those with terminal malignancies, but has rarely been noted in burn patients. Recognition of the seriousness of the problem and the aggressive antibiotic therapy appropriate to the organisms in question is advised. PMID- 8216776 TI - Butter in the initial treatment of hot tar burns. AB - Hot tar adheres to skin and produces burns of variable depth. Removal of the tar is not essential but it improves patient comfort and allows early assessment of the underlying tissue damage. Butter is readily available and is an effective method of removing the adherent tar. PMID- 8216777 TI - Specific pattern burn in a psychiatric patient. AB - Position at the time of burning can be precisely determined by analysis of the depth, configuration, distribution of the burn, flexion creases and spared areas. This information is very useful in determining non-accidental injuries in children. Although specific pattern injuries are rare in adults, we report an example of a self-inflicted burn in a schizophrenic which resembles a 'forced immersion burn'. PMID- 8216778 TI - Salvage of a patient with burn inhalation injury and pancreatitis. AB - A multidisciplinary approach by the staffs of the Emergency Department and the Regional Burn Center saved the life of a burn patient with an inhalation injury and pancreatitis. This successful treatment is attributed to ventilatory management using fibreoptic bronchoscopy in the Emergency Department, followed by burn eschar excision with coverage by cultured skin and non-operative management of an enlarging pseudocyst by percutaneous transgastric drainage. PMID- 8216779 TI - Arterial embolization in the treatment of Curling's ulcer bleeding in a burn patient. AB - Curling's ulcer bleeding is a well-known life-threatening complication of the severely thermally injured patient. This report describes a successful left gastric artery embolization in a 70 per cent total body area burn patient with severe gastric bleeding. We discuss the various non-surgical invasive modalities for treating such patients, and emphasize the advantages of arterial embolization over surgery. PMID- 8216781 TI - [A comment on two medicinal aroids huzhang and tiannanxing]. AB - An original error on Huzhang and Tiannanxing in Li Shizhen's "Bencao Gangmu" (Compendium of Materia Medica, 1596) is corrected in this paper. The conclusion is that Huzhang in "Shen Nong's Materia" (around 200) should be the tuber of Pinellia pedatisecta and Tiannanxing in "Kaibao Bencao" (974) the tuber of Arisaema heterophyllum but they were merged or confused by Li Shizhen. The former, in fact, has been cultivated, marketed, exported and used medically for its high quality, but it has disappeared from herbal literatures owing to Li's error. Therefore, the above-mentioned correction should be accepted in the next edition of Pharmacopoea of the people's Republic of China. PMID- 8216780 TI - Very deep burns of the hand due to low voltage electrical laboratory equipment: a potential hazard for scientists. AB - A low voltage (24 V) electrical deep burn of the hand injured a professor of applied physics when performing an experiment in his laboratory. The potential hazard of the equipment is described, the injuries are reported and the literature is reviewed. PMID- 8216782 TI - [Studies on numerical taxonomy of Smilacaceae plants in Zhejiang Province by pyrolysis-high resolution gas chromatography]. AB - The best taxonomic results were obtained in the analysis of rhizomes of 9 species and 1 variety of Smilacaceae plants grown in Zhejiang Province by using pyrolysis high resolution gas chromatography and numerical taxonomy. When compared with the result of thin layer chromatography, it was found that those by classical taxonomy were basically reasonable, but Smilax china should be divided into two types: one with big berries and the other with small berries. PMID- 8216783 TI - [Studies on the quality of fructus Evodiae]. PMID- 8216784 TI - [Comparison of chemical constituents between new and old processed products of rhizoma Typhonii]. AB - Experimental results showed that the original contents of chemical constituents in the new processed products were higher than those in the old one, while the content of assistant alum in the new products was lower than that of the old one. It is thus confirmed that the new processing technology is reasonable. PMID- 8216785 TI - [A preliminary experimental study on processing of peach kernel]. AB - Contents of water, alcohol, ether soluble components and amygdalin of differently processed peach kernel (raw drug, scalded, stir-baked and steamed) were determined. The security of the decoctions from the four processed samples was compared. This paper provides a preliminary experimental basis for the rational utilization of peach kernel. PMID- 8216786 TI - [The effect of processing on the content of toxic constituent arsenic in magnetitum]. AB - The experimental results reveal that arsenic content in pig magnetitum is about 5 25 times as in the calcinated samples. Therefore the toxic effect of magnetitum can be eliminated or reduced after it is calcinated. PMID- 8216787 TI - [Studies on percutaneous absorption of ruyi jinhuang san patcher with radioisotope tracer]. AB - Berberine is one of the active ingredients in Ruyi Jinhuang San Patcher. With 3H berberine as the tracer, a radio-labelled method was used for determining percutaneous rate and drug concentration of berberine in plasma in vivo and in vitro. A study on the percutaneous rate of different technological plasters and various animal skins was also carried out. PMID- 8216788 TI - [Determination of trace elements in several hemostatic medicinal plants and their boiling water extracts]. AB - The experimental results indicate that the amounts of Cu, Zn, Fe and Mn in Rubia cordifolia and Agrimonia pilosa var. japonica are very small in boiling water extracts (only 6%). But after digestion they may rise to 30%. It was found that the amounts of four trace elements decreased with the increase of extracting time, but the ratios of Mn/Zn and Zn/Cu were almost the same. PMID- 8216789 TI - [Studies on constituents of Ilex chinensis Sims]. AB - Several compounds characterised as protocatechuic acid, caffeic acid, syringin, rotundic acid and pedunculoside were isolated from the leaves of Ilex chinensis, a Chinese crude drug. A novel compound cyclohexanone pedunculosyl-3,23-O-acetal was identified and proposed as a pedunculoside derivative produced in the extracting procedure. PMID- 8216790 TI - [Isolation and identification of alkaloids from Fritillaria egregia Y.K. Yang, J.Z. Wu et D.T]. PMID- 8216791 TI - [Studies on chemical constituents of Marsdenia oreophila]. PMID- 8216792 TI - [Immune function of guifudihuang pills (GFDH) and their oral liquid preparation]. AB - Experimental observation was made on the effect of GFDH pills and their oral liquid preparation on thymus and spleen weight, formation of the antibody haemolysis plaque and phagocytic function of the macrophages of peritoneal cavity. The result revealed that both GFDH pills and their oral liquid preparation were found helpful to the enhancement of immunological function. The oral liquid preparation also increased markedly the plasma level of testosterone in immature rats. PMID- 8216793 TI - [Studies on laxative function of maren soft capsule]. AB - The experimental results show that the Maren soft capsule can increase the amount and weight of the stool of normal mice and model mice with dry stool, promote the advanced percentage of charcoal powder in the small and large intestines of mice, enhance the movement of the smooth muscle of isolated ileum of guinea pigs under physiological conditions or low temperature, as well as strengthen the intestinal movement in rabbits. PMID- 8216794 TI - [Comparison of the effect of sijunzi decoction, siwu decoction and bazhen decoction on immune function in mice]. AB - Sijunzi decoction, Siwu decoction and Bazhen decoction can antagonize the suppressive effect of hydrocortisone on proliferation of lymphocyte by spleen cells in C57BL/6J mice in vitro, and of the three decoctions Sijunzi works best. Sijunzi Decoction can antagonize the suppressive effect of cyclophosphamide on the delayed cutaneous hypersensitivity (DCH) induced by DNCB in mice and the production of hemolysin in mice immunized with SRBC. The three prescriptions all can enhance the clearance rate of iv charcoal particles as well as bone marrow cells inhibited by cyclophosphamide in mice, but Sijunzi decoction functions best of all. PMID- 8216795 TI - [Theory of the regeneration of the cortex of Eucomnia ulmoides Oliv after peeling and related techniques]. PMID- 8216796 TI - [Study on the history of the processing of semen Strychni]. PMID- 8216797 TI - [Conservation methods for germplasm of medicinal plants]. PMID- 8216798 TI - [Microscopic identification of Chinese herbal medicine xuduan]. PMID- 8216799 TI - [Temperature requirements for afterripening of the embryo of Fritillaria cirrhosa Don.f]. AB - The seeds of Fritillaria cirrhosa contain immature embryos at harvest. To afterripen the embryos, different temperatures are required at different stages. Experiments show that 15 degrees C is the most suitable temperature for the earlier stage of morphological development of the embryos, and 10 degrees C for the later stage. To release from the physiological dormancy, chilling at 5 degrees C for 73-91 days is desirable. PMID- 8216800 TI - [New techniques of cultivating Ganoderma lucidum (W. Curt.:Fr)Karst.,Rev. with woodlog]. AB - Imitating wild cultivation of Ganoderma lucidum with short-woodlog is a method of cultivating artificial G. lucidum developed in recent years. The method can be applied to large scale production. This paper shows that section-inoculating and impregnating with steamed shortwoodlog indoors and soil-cover cultivating under large shed are important in the cultivation. PMID- 8216801 TI - [Determination of aconitine in wutou and related herbal drugs (roots of Aconitum) and their processed products in Hong Kong market]. AB - This paper deals with the determination of the poisonous aconitine-type alkaloids in roots of Aconitum in Hong Kong market by TLC scanning. The results show that the content of aconitine was 0.0041%-0.021% in processed roots of Aconitum carmichaeli, 0.0084%-0.034% in processed roots of A. kusnezoffii; 0.0012% and 0.0007% in crude and roasted lateral tuber of A. carmichaeli. Aconitine was not found in the processed product of Fuzi. PMID- 8216802 TI - [Optimization of the preparing process for sinitang drop pills by orthogonal test]. AB - The preparing process for Sinitang drop pills was optimized by orthogonal test. The results from nine experiments were subjected with three indexes to objective analysis and variance analysis, and an optimum preparing process for Sinitang drop pills was sieved out. The quality of the drop pills prepared in this way was examined to be up to the standard. PMID- 8216803 TI - [Anti-platelet activating factor constituents, 2,5-diaryltetrahydrofuran type lignans, from Piper futokadsura Sied. et Zucc]. AB - Besides the known components kadsurenone, futoquinol and futoxide, three anti platelet activating factor principles have been found from the stem part of Piper futokadsura (Piperaceae), the Chinese drug haifengteng. They were separated and identified as galgravin, galbelgin and veraguensin on the basis of HPLC and spectral analysis. The natural existence of these three anti-PAF constituents in haifengteng is reported for the first time. PMID- 8216804 TI - [GC-MS analysis of the essential oil from the root of Ligusticum brachylobum Franch]. AB - The constituents of the essential oil of the root of Ligusticum brachylobum have been analysed by gas chromatography-mass spectrometry qualitatively and gas chromatography quantitatively. Forty-five compounds were identified. The main constituent of the oil is alpha-pinene. PMID- 8216805 TI - [Chemical constituents of the fruit of Panax ginseng C. A. Meyer]. AB - Four compounds were isolated from the fruit of cultivated Panax ginseng and identified as beta-sitosterol,20(R)-protopanaxatriol, daucosterine and 20(R) ginsenoside-Rg3 on the basis of physicochemical constants and spectral evidences. PMID- 8216806 TI - [HPLC determination of iridoids in Cape jasmine Frvit (Zhizi)]. AB - Four iridoid constituents: geniposide, gardenoside, geniposidic acid and genipin 1-beta-gentiobioside, have been separated by using an ODS (7 microns) column with gradient elution. The iridoid contents of the crude drug were quantified by peak height ratio. Thirty-one specimens from various sources were analyzed. PMID- 8216807 TI - [Metabolism and pharmacokinetics of ferulic acid in rats]. PMID- 8216808 TI - [Effect of calculus bovis on immune functions in mice]. PMID- 8216809 TI - [Anti-inflammatory effect of Caragana microphylla Lam]. AB - Caragana microphylla can antagonize the inflammation induced by carrageenin, hot water and croton oil. It can also inhibit the proliferation of granuloma, blood capillary permeability, phagocytic function of mononuclear phagocyte system, and synthesis or release of PGE2 at the inflamed part. PMID- 8216810 TI - Whey protein concentrates and isolates: processing and functional properties. AB - Substantial progress has been made in understanding the basic chemical and structural properties of the principal whey proteins, that is, beta-lactoglobulin (beta-Lg), alpha-lactalbumin (alpha-La), bovine serum albumin (BSA), and immunoglobulin (Ig). This knowledge has been acquired in terms of: (1) procedures for isolation, purification, and characterization of the individual whey proteins in buffer solutions; and (2) whey fractionation technologies for manufacturing whey protein concentrates (WPC) with improved chemical and functional properties in food systems. This article is a critical review of selected publications related to (1) whey fractionation technology for manufacturing WPC and WPI; (2) fundamental properties of whey proteins; and (3) factors that affect protein functionality, that is, composition, protein structure, and processing. PMID- 8216811 TI - Recent advances in structure and function of food proteins: QSAR approach. AB - QSAR (quantitative structure-activity relationship), widely used in chemistry with hydrophobic, electronic, and steric parameters as structural factors, was found to be appropriate for use with food proteins, despite the difficulty, due to the complexity in macromolecular structure, in defining the steric terms. Emulsifying ability was closely related to hydrophobicity, and incorporation of solubility to hydrophobicity as factors improved the R2 of regression analysis. Foaming activity required both hydrophobicity and other factors pertaining to the adsorption of proteins at the interface in order to obtain adequate foam lamella strength. Hydrophobicity as well as other factors relating to the intermolecular interactions, for example, Ca and SH are involved in thermally induced gelation. For breadmaking, although no extensive QSAR work had been carried out, the important function of high molecular glutenin subunits was confirmed, and, notably, the critical function of hydrophobicity in breadmaking also was demonstrated. PLS (partial least-squares regression) and neural networks classify more correctly than other multivariate techniques, thereby yielding higher r2 values in modeling and prediction. However, multiple regression analysis and PCR (principal component regression) also were found to be effective for modeling because the information useful in elucidating the mechanism of protein function could be readily obtained. A characteristic property of unsupervised learning techniques, especially PCS (principal component similarity analysis), in identifying influential factors in the function mechanisms was demonstrated. PMID- 8216812 TI - Encapsulation of food ingredients. AB - Microencapsulation is a relatively new technology that is used for protection, stabilization, and slow release of food ingredients. The encapsulating or wall materials used generally consist of starch, starch derivatives, proteins, gums, lipids, or any combination of them. Methods of encapsulation of food ingredients include spray-drying, freeze-drying, fluidized bed-coating, extrusion, cocrystallization, molecular inclusion, and coacervation. This paper reviews techniques for preparation of microencapsulated food ingredients and choices of coating material. Characterization of microcapsules, mechanisms of controlled release, and efficiency of protection/stabilization of encapsulated food ingredients are also presented. PMID- 8216813 TI - Enhanced liver MR: contrast agents and imaging strategy. AB - Contrast enhancement in liver MR can be achieved by a variety of fundamentally different strategies. The published clinical literature regarding Gd DTPA (gadopentetate dimeglumine), Gd HP-DO3A (gadoteridol), Gd BOPTA (gadobenate dimeglumine), Mn DPDP, and AMI-25 is reviewed, followed by a brief discussion of two new iron particulate agents currently in preclinical trials. Different imaging techniques also must be used for visualization of contrast enhancement depending on the specific type of agent utilized. With both gadolinium and manganese chelates, T1 weighted sequences are used to visualize the effect of the contrast agent. There is positive enhancement (an increase in signal intensity) of normal liver parenchyma post-contrast due to enhanced T1 relaxation. With iron particulate agents, T2 weighted sequences are used. In this instance, there is negative enhancement (a decrease in signal intensity) of normal liver post contrast due to enhanced T2 relaxation. Clinical use at present is limited to the extracellular gadolinium chelates, with bolus injection and dynamic imaging improving efficacy. Current research also supports the use of a high dose (0.3 mmol/kg) for improved lesion detectability, a finding now clinically relevant due to the recent approval of Gd HP-DO3A at both standard and high doses. PMID- 8216814 TI - MRI of the knee: practical imaging techniques and abnormalities. AB - Magnetic resonance imaging of the structures of the knee joint can be performed rapidly with current commercially available instruments. This article outlines methods for obtaining comprehensive clinical imaging studies within a 30-min time frame and reviews the MR appearance of knee joint disorders. PMID- 8216815 TI - Spiral CT of the abdomen: clinical applications. AB - Spiral CT is a technique for rapid scan acquisition. It involves continuous scanning as the patient is advanced at a constant rate through the CT gantry. This eliminates interscan delay and the gap between scan slices. The acquired scan is a volume dataset, resulting in improved multidimensional displays. The entire abdomen is scanned within approximately 30 s, so that optimal contrast dynamics for evaluation of the vasculature are easily obtained. High levels of parenchymal enhancement are readily achieved throughout the duration of the scan. These factors also contribute to the improved quality of the multidimensional displays. In this article, applications and clinical experience with spiral CT in the abdomen are reviewed. PMID- 8216816 TI - CT evaluation of breast cancer: spectrum of disease. AB - Breast cancer is the second most common cancer in women. Although computed tomography is not typically used as a primary diagnostic modality for detection of a breast mass, it is playing an increasing role in the accurate staging of breast cancer as well as in determining patterns or recurrence. This article reviews the role of CT in the evaluation of breast cancer with specific emphasis on the varying patterns of disease recurrence. Specific emphasis is placed on complications and recurrences in the chest, axilla, the abdomen (including involvement of the major abdominal organs), as well as the musculoskeletal system. Specific case examples illustrating the various pathologic processes involving patients with breast cancer are presented. PMID- 8216817 TI - Localization of the angiogenesis inhibitor thrombospondin in human synovial tissues. AB - Recently, we have shown that a macrophage subpopulation isolated from the synovial tissue of patients with rheumatoid arthritis was potently angiogenic and that a secreted inhibitor of angiogenesis, which is controlled by a tumor suppressor gene in hamster cells, was similar to thrombospondin. In order to investigate the potential role of thrombospondin in human arthritic disorders, we employed immunohistochemistry to examine frozen synovial tissue sections from normal controls (n = 3), patients with rheumatoid arthritis (n = 14) and with osteoarthritis (n = 5). The synovial tissues were stained with monoclonal antibody (mAb) A2.5, which reacts with the heparin-binding domain of thrombospondin, mAb A6.1, which reacts with the epidermal growth factor repeat motif of thrombospondin, and with mAb A4.1, which reacts with the properdin repeat domain of thrombospondin. In rheumatoid synovial tissues the anti thrombospondin mAbs reacted with vascular endothelial cells, and to a lesser extent with vascular smooth muscle. Pericytes were stained, particularly with mAb 6.1. Reactivity was also found with isolated macrophages and with the macrophage derived synovial lining layer in over half the tissues. In osteoarthritis synovial tissues, mAb A2.5 stained fewer macrophages than in rheumatoid arthritis synovial tissues. Slightly fewer blood vessels reacted with mAb A2.5 in normal compared to diseased synovia. The mAbs reacted with capillaries, venules and arterioles in all synovial tissues. We conclude that mAbs to thrombospondin react primarily with blood vessels and macrophages in synovial tissues. Perhaps thrombospondin may function as an adhesive glycoprotein mediating cellular interactions, or it may serve to counteract the effects of the angiogenic factors produced by cells within diseased synovial tissues. PMID- 8216818 TI - Distribution of expression of cell adhesion molecules in the mid to late gestational mouse fetus. AB - The control of murine morphogenesis appears to be regulated in part by the expression of the primary cell adhesion molecules, such as the neural cell adhesion molecules (N-CAM). Here we show that the epithelial cell adhesion molecules appear in intestinal epithelium, liver and cartilage, but were absent from intestinal submucosa and neural tissues. N-CAMs on the other hand were present in intestinal submucosa and neural tissues, but absent from intestinal epithelium, liver, and cartilage. Both epithelial cell adhesion molecules and N CAM were present in intestinal primordium at gestation times (days 12 and 13) when intestinal epithelium and submucosa are not morphologically distinguishable. On day 14 of gestation, when the intestinal epithelium and submucosa are morphologically distinguishable, epithelial cell adhesion molecules are present in intestinal epithelium but not submucosa while N-CAM has the reciprocal pattern of expression. Immunoblots with antibodies to N-CAM revealed two bands of 110-220 and 60 kD which followed specific patterns of expression. As defined by densitometry, the intensity of the larger protein increased from day 12 to 18 in neural tissue groups, but diminished in late gestational intestine and intact fetus and was replaced by a more discrete region of 110-150 kD, suggesting that embryonic to adult conversion of isoform ('E to A conversion') had occurred at this nonneural site. PMID- 8216819 TI - Carcinoembryonic antigen and related glycoproteins in psoriasis. AB - Psoriasis is a benign but hyperproliferative skin disease. Psoriatic basal cells show a phenotype similar to that of normal skin, while psoriatic suprabasal cells exhibit a qualitatively altered keratinization pathway, resulting in the absence of the granular layer. These cells further show an abnormal expression of cellular differentiation antigens, which does not lead to tumor development. This immunohistological study demonstrates the appearance of carcinoembryonic antigen (CEA) in psoriatic suprabasal cells below the parakeratotic layer, while other markers such as CEA-related antigens, the nonspecific cross-reacting antigens and alpha-fetoprotein are not expressed. CEA is absent in normal skin, lichen planus, ichthyosis vulgaris and allergic dermatitis. Our data support the notion that dedifferentiation of psoriatic suprabasal keratinocytes is due to the reactivation of early developmental patterns of differentiation in this disease. PMID- 8216820 TI - Morphologic analysis of three-dimensional tumors developed in fibrin matrix and agar culture system. AB - The three-dimensional growth of cultured tumor cell lines (HT29, a colon adenocarcinoma cell line; M21, a melanoma cell line; KB, a nasopharyngeal carcinoma cell line) has been investigated in an agar culture system with a fibrin matrix in vitro. The tumor cells developed to tumors 3 x 3 mm in diameter after 10 days in culture in vitro. This size was large enough to allow histologic examination. The tumor cells located in the surface area of the three-dimensional tumor seemed to grow well. However, the tumor cells in the center degenerated or did not proliferate, indicating a lack of nutrition and/or anoxia in the center. The histologic comparison between the xenografted tumors on nude mice and the three-dimensional tumors in vitro suggests that the structures of the three dimensional tumors were comparable, especially in the surface area, to the xenografted tumors. Furthermore, the antitumor effect of mitomycin C on the three dimensional tumors was found to be dose-dependent. PMID- 8216822 TI - Proliferative responses of peripheral blood lymphocytes of mice and humans stimulated with recombinant interleukin 2. AB - In vitro proliferative responses of human and murine peripheral blood lymphocytes (PBL) were studied. The cells were stimulated with recombinant interleukin 2 (IL 2) or with a mixture of phorbol-13-myristate-12-acetate with either IL-2 or calcium ionophores. Proliferation of human PBL could be induced by doses of human IL-2 or phorbol that were much lower than those required to produce responses of murine cells. However, the magnitude of the responses of human PBL was definitely lower than that of the responses of murine PBL. Murine IL-2 did not induce proliferation of human PBL, but it synergized with phorbol. The responses of murine PBL reflected the previously described strain differences in responses of spleen cells that were shown to be under complex polygenic control. The proliferation of murine spleen cells could be induced with human, as well as murine IL-2, and both species of IL-2 synergized with phorbol. While no clear-cut low and high responders could be identified among normal healthy human subjects, 2 individuals produced consistently low responses to IL-2 and 1 individual displayed low responses to phorbol and calcium ionophore A23187. Available data suggest, but do not allow a firm conclusion, that proliferative responses of human PBL are under genetic control, perhaps as complex as that reported for mice. PMID- 8216821 TI - Monoclonal antibody MS-44B reacts with human dendritic, glial and endothelial cells: differential expression of MS-44B antigen by epidermal dendritic cells and by MS-1+ splenic sinusoidal endothelial cells. An immunohistological study. AB - Rat monoclonal antibody MS-44B was raised against the dendritic human melanoma cell line SK-Mel 25 and detects highly dendritic cells and endothelial cells in various human organs. Among the cells recognized are dendritic cells in lymphoid organs, such as lymph node, tonsil and spleen, dendritic cells in skin, lung and lamina propria, (astro-)glial cells in the central nervous system and mesangial cells in the kidney. In peripheral lymph nodes (and less consistently in visceral lymph nodes), MS-44B reactive cells are found predominantly in the paracortical area and in the region of the marginal sinus; in tonsils these dendritic cells are concentrated at the outer rim of the follicle, while their distribution in the white pulp of the spleen is less well defined. In skin, both dermal and epidermal dendritic cells are stained. In the dermis just beneath the dermal epidermal border, dendritic cells may be found with their processes protruding into the epidermal basal layer. MS-44B reactive epidermal dendritic cells send their processes in a horizontal direction or into the upper epidermal cell layers. MS-44B reactive epidermal dendritic cells are neither Langerhans cells, since they lack HLA-DR antigens and CD1, nor Merkel cells, since they lack cytokeratin expression. They rather seem to constitute a subpopulation of epidermal melanocytes that are low in tyrosinase expression and do not populate the melanocyte area of the hair bulb. With regard to the endothelium, monoclonal antibody MS-44B reveals marked heterogeneity in that it preferentially stains the endothelium of large and medium-sized arterial vessels, while capillary and venous endothelia are less well stained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216823 TI - Protoberberine alkaloids from Enantia chlorantha therapy of allyl-alcohol- and D galactosamine-traumatized rats. AB - The short-term effect of the hepatotoxins allyl alcohol (AA) and D-galactosamine (GalN) was investigated in adult female rats. In addition, the curative effect of Hepasor, protoberberine extract from Enantia chlorantha was examined 3 days following traumatization. There was a significant increase in serum alanine transferase (ALT) and serum alkaline phosphatase (APHOS) values induced by AA traumatization, which were lowered following Hepasor treatment. GalN traumatization also significantly increased ALT values, APHOS values to a lesser extent, and produced a decrease in serum hydroxyproline (OH-PRO) values. Hepasor treatment prevented these changes. Liver biopsies of AA-traumatized rats revealed marked necrotic areas and increased numbers of binuclear cells. When AA traumatization was combined with Hepasor treatment, fewer morphological changes in the liver were observed. GalN also provoked a 3-fold increase in binuclear cells, about a 10-fold increase in the number of lymphocytes and an increase in the neutrophils in the liver. Notable changes in Kupffer cells and degenerating hepatocytes were also observed. Both GalN traumatization and Hepasor treatment on pretraumatized rats nearly abolished these changes. Hepasor treatment appears to prevent chemically induced traumatization and also to promote the healing process in the hepatic injury models selected. PMID- 8216824 TI - Cell-specific expression of a recombinant rat glutathione S-transferase Ya gene in transgenic mice. AB - Transgenic mice have been generated which carry a cDNA encoding the rat Ya isozyme of glutathione S-transferase (GST) under the transcriptional control of the SV40 early region promoter-enhancer. Expression of the GST transgene was highly tissue-specific, with the highest expression detected in the convoluted tubular epithelium of the mouse kidney cortex. GST Ya mRNA abundance in these cells was greater than that found for GST Ya mRNA in normal rat liver. GST Ya protein was observed in the convoluted tubule cells of the founder mouse as well as an F1 offspring. The transmission of the foreign gene was followed for two generations, and an erratic pattern of inheritance was observed. These animals provide a model for the in vivo study of GST modulation of carcinogenesis and drug toxicity. PMID- 8216825 TI - Influence of cobalamin on the survival of mice bearing ascites tumor. AB - The effect of cobalamin (vitamin B12) on the survival time of mice bearing P388 leukemia has been examined. Among the three cobalamins studied, the enzymatically active derivatives, methylcobalamin and 5'-deoxyadenosylcobalamin, were able to significantly increase the survival time of mice implanted intraperitoneally with the tumor cells. The pharmaceutical form, cyanocobalamin, was not active. The antitumor activity of these cobalamins may be associated with their functions in metabolism. PMID- 8216826 TI - Genomic instability and metastatic progression. AB - Recently, there has been a growing body of opinion that tumour cells progress from a less malignant to a more malignant (metastatic) phenotype, due to an inherent instability within the genome. It has also been suggested that genomic instability and the rate of generation of metastatic variants both increase as the tumour cells achieve a higher state of malignancy. In this review, several different aspects of genomic instability have been discussed with particular reference to the low (F1) and high (BL6, ML8) metastatic variants of a B16 murine melanoma. The induced mutation frequency, gene amplification, and sister chromatid recombination correlated with the order of metastatic potential. Survival data for x-irradiation and bleomycin were similar between the three cell lines. When these agents were used to induce strand breakage, no difference was detectable in either the rate or extent of DNA single or double strand break repair. The fidelity of double strand break religation was measured using the PMH16 plasmid, and the frequency of homologous recombination was measured using the DR plasmid. Surprisingly, both of these parameters showed a correlation with metastasis which was opposite to the expected result, with regard to the concept of genomic instability. A basis for this might be the functional heterogeneity within the cell lines in respect of the properties measured. Therefore, some aspects of instability may have to be measured at a more critical level if they are to be of value in estimating the inherent instability of the genome. PMID- 8216827 TI - Chimeric drift in blood cell populations of chimeric rats constructed between congenic strains. AB - Chimeric drift is the shift in the proportion over time of the two cell lineages which comprise a chimera (genetic mosaic). Chimeric drift in blood cell populations is determined by both the probability of proliferation from stem cell pools of one or the other of the cell lineages which constitute the chimera and the effects of life span in circulating blood cells. Previous evidence suggests that while chimeric drift occurs in chimeras between genetically disparate strains, it does not occur when the strains used are closely related. No information is available from chimeras between congenic strains. In the present study, chimeric rats were produced between strains with distinguishable class I major histocompatibility complex haplotypes, PVG-RT1a and PVG (which express the haplotype RT1c). PVG-RT1a-specific monoclonal antibodies were used to establish the mosaic patterns in the cell populations of peripheral blood by fluorescein activated cell sorting. Mosaic cell lineage of red blood cells, white blood cells, lymphocytes, monocytes and neutrophil populations were analyzed weekly over a period of 6 weeks. The ratio of cells of the PVG-RT1a lineage to cells of the PVG lineage shifted either in favor of PVG-RT1a or PVG in cellular components of peripheral blood. The percentage of PVG-RT1a cells in peripheral blood of chimeras changes by as much as 54, 28, 21, 19 and 23% in red blood cell, white blood cell, lymphocyte, monocyte and neutrophil populations, respectively. The shifts in the percentage of PVG-RT1a cells appears to occur in a cyclic fashion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216828 TI - Adherence in combination with lipopolysaccharide, tumor necrosis factor or interleukin-1 beta potentiates the induction of monocyte-derived interleukin-8. AB - In this study we demonstrate that adherence of peripheral blood mononuclear cells (PBMC) to either plastic or extracellular matrix, such as collagen type I or fibronectin, is a significant stimulus for the induction of both interleukin-8 (IL-8) mRNA and antigen. In addition, adherence of PBMC in the presence of lipopolysaccharide, interleukin-1-beta, or tumor necrosis factor-alpha greatly enhances transcription/translation of IL-8 from these leukocytes. Our findings demonstrate that PBMC adherent to either plastic or physiological surfaces in combination with an inflammatory agonist is both a potent and efficacious signal for the expression and production of the neutrophil chemotactic/activating cytokine, IL-8. PMID- 8216829 TI - Myelotoxicity of rifabutin and 3'-azido-3'-deoxythymidine, alone and in combination, to human hematopoietic progenitor cells in vitro. AB - Mycobacterial infection is a common complication of acquired immunodeficiency syndrome (AIDS) frequently requiring antimycobacterial medication. It was of interest to determine if one such agent, rifabutin, could be tolerated by AIDS patients in conjunction with 3'-azido-3'-deoxythymidine (AZT) therapy. We evaluated the in vitro myelotoxic effects of rifabutin on human hematopoietic progenitor cells, alone and in combination with AZT (rifabutin: AZT, 1:10 ratio) over a range of concentrations in a microcapillary assay. Both rifabutin and AZT at 5 microM were moderately toxic to hematopoietic progenitors, inhibiting colony formation by 57-65% and 59-63%, respectively. The combination of rifabutin (5 microM) and AZT (50 microM) inhibited colony formation by 59-73%. Granulocyte macrophage progenitors were less sensitive to this combination than erythroid progenitors. The combination of ribabutin and AZT did not exceed the in vitro myelotoxicity to human progenitors of AZT alone. These results suggest that rifabutin may be tolerated in AIDS patients, with no anticipated increase in myelotoxicity when given with AZT. PMID- 8216831 TI - Accurate flow cytometric measurement of bacteria concentrations. AB - Accurate measurements of bacteria concentrations are required in numerous studies; they raise methodological problems that complicate, for instance, the investigations of polymorphonuclear neutrophil functions. We propose a new flow cytometric method of determining bacteria concentrations by comparison with a standardized fluorescent latex bead solution. Relative counts of beads and bacteria are established in a system using both fluorescence and light scatter for the two types of particles. On the one hand, the latex bead size (0.98 microns in diameter) permits counting on traditional hematological counters and, on the other, a flow cytometric detection with the same conditions for bacteria. The reproducibility of the study of bacteria concentration measurements gave a coefficient of variation of < 5%. PMID- 8216830 TI - Proteoglycan synthesis by the neointimal smooth muscle cells cultured from rabbit aortic explants following de-endothelialization. AB - Proteoglycans (PGs), the essential component of the extracellular matrix, are implicated in the pathogenesis of atherosclerosis. In an experimental model of injury, PGs accumulate in the neointimal tissue parallel with lipid deposition. However, it is still not clear whether the PG accumulation is from active smooth muscle cell (SMC) production or is a consequence of trapping within neointima covered by endothelium. To study the effect of endothelial injury on PG synthesis, SMCs were cultured from normal aorta (N-SMC), neointima covered by regenerated endothelium (W-SMC) and neointima without endothelium (B-SMC). Using [35S]-Na2SO4, as a precursor in an in vitro incubation, the kinetics of PG synthesis were determined. PG synthesis by all three cell types increases as a function of time. It is significantly higher in the SMCs cultured from endothelium-denuded aortic explants (W- and B-SMC) than N-SMC. This finding indicates that endothelial injury stimulates PG synthesis by SMCs. PMID- 8216832 TI - Type I collagen synthesis in cultured aortic smooth muscle cells from spontaneously hypertensive rats and normotensive control, Wistar-Kyoto rats. AB - An inhibition ELISA was used to quantify the amount of type I collagen synthesized in culture media and cell layers from aortic smooth muscle cells (SMCs) of spontaneously hypertensive rats (SHR) and normotensive control, Wistar Kyoto rats (WKY). Cultured cells were also observed by electron microscopy. Collagen content in the culture media was strongly increased after 6 days in both cultures. Collagen and protein contents in the medium and cell layer from SHR were significantly higher than those in WKY at day 14. However, cell density in SHR-derived cells was also higher than that of WKY. No significant differences were detected in the rates of collagen content between SHR and WKY on a per cell basis. The main differences between SHR and WKY in collagen and protein levels may be due to the greater number of SHR cells and increased amounts of extracellular matrix components. The assay system outlined here should be useful for studying the control of extracellular-matrix synthesis. PMID- 8216833 TI - Expression of tissue kallikrein in normal and SV40-transfected human endometrial stromal cells. AB - The polymerase chain reaction with specific tissue kallikrein primers was utilized to demonstrate the presence of tissue kallikrein mRNA in human endometrial stromal cells. Enzymatic analysis measured with a specific tripeptide nitroanilide substrate demonstrated the presence of tissue kallikrein in the conditioned medium obtained from both normal stromal cells and stromal cells transfected with an origin-defective temperature-sensitive SV40 large T antigen. The transfected stromal cell supernatant exhibited approximately twice as much tissue kallikrein activity as normal stromal cells at 60-100% of cell confluence. The release of tissue kallikrein from transfected stromal cells was confirmed by Western blot analysis and [35S]-methionine incorporation into a 35-kD protein which retains tissue kallikrein activity. These results demonstrate for the first time the expression and secretion of tissue kallikrein in human endometrial stromal cells and provide evidence of possible involvement of tissue kallikrein in cell transformation. PMID- 8216834 TI - CD23 isoforms in murine T and B lymphocytes. AB - A major objective of the present studies was to seek biochemical evidence for the production of the low affinity IgE Fc receptor (CD23) by murine T cells. These studies have established that most of the murine T cell populations analyzed express CD23 mRNA. Some T cell populations contained a transcript whose nucleotide sequence was identical to that previously reported for the CD23 cDNA cloned from murine B cells. Some T and B cells contained CD23 transcripts lacking exon-3-encoded sequences. If translated, these transcripts would yield a CD23 polypeptide lacking the transmembrane segment and all but six amino acids of the intracytoplasmic tail. The truncated CD23 transcripts detected in T and B cells in these studies appear to be generated via alternative splicing. It is possible that these transcripts encode soluble, secretory forms of CD23, or that these transcripts have regulatory functions that influence CD23 gene expression. These investigations provide new information about the structure of murine lymphocyte CD23, they predict the occurrence of CD23 isoforms in the mouse, and they present direct evidence for the production of CD23 by murine T lymphocytes. PMID- 8216835 TI - Identification of conformational epitopes of the BPV-1 capsid recognized by competitive inhibition of sera from infected or immunized animals. AB - Conformational papillomavirus (PV) capsid epitopes are the major targets of neutralizing antibodies. BPV1 virion surface epitopes were analyzed for type specificity, induction of neutralization, and topographical location with antibodies from selected humans, and BPV1 or -2 immunized or infected cattle, rabbits and mice. Rabbit sera produced against deer PV (DPV) or BPV2 and human sera reacted with intact BPV1 in ELISA, indicating the presence of cross-reactive conformational epitopes on the surface of BPV1 virions. However, competitive binding assays performed on intact BPV1 capsids using unlabeled and biotin conjugated antibodies revealed that the conformational epitopes of BPV1 recognized by rabbit, bovine and human antibodies were topographically different. Only hyperimmune sera to intact BPV1, BPV2 or DPV neutralized BPV1-induced focus formation of C127 cells with the highest neutralizing titers observed for bovine and rabbit antibodies produced against intact BPV1. Our study showed the complexity of conformational capsid epitopes of BPV1 and their importance for inducing a protective humoral immune response in animals inoculated or immunized with BPV1. PMID- 8216836 TI - Characterization of cells of the myeloid-monocytic lineage (ML-1, HL-60, THP-1, U 937) chronically infected with the human immunodeficiency virus-1. AB - The myeloid-monocytic cells ML-1, HL-60, THP-1 and U-937 were chronically infected (for more than 2 years) with the lymphotropic HIV-1 strain HTLV-IIIB. Reinfection experiments revealed that viruses obtained from chronically infected ML-1/HIV-1 and HL-60/HIV-1 cells show a low infectivity if tested with uninfected ML-1 and HL-60 cells in contrast to virus preparations from chronically infected THP-1/HIV-1 and U-937/HIV-1 with their corresponding uninfected cell lines. Analyses of selected cell surface markers showed a differential expression of CD4, CD8, CD11c, CD14, CD15, CD20, HLA-DR and HLA-DQ in non- or chronically infected cells. During chronical infection, the myeloid-monocytic cells lost their reactivity with peroxidase and esterase. In chronically infected cells, the steady-state levels for TNF-alpha mRNA remained unchanged while those for IL-6 decreased. The half-lives of transcripts of both TNF-alpha (t1/2: 70 min) and IL 6 (t1/2: 100 min) were nearly the same in uninfected and chronically infected HL 60 cells. PMID- 8216837 TI - Pathogenesis of mesothelial reactions to asbestos fibers. Monocyte recruitment and macrophage activation. AB - Exposure to asbestos fibers leads to a variety of mesothelial reactions: pleural effusions, fibrotic pleural plaques, and malignant mesotheliomas. An animal model was developed to reproduce these lesions in C57B1/6 mice using weekly intraperitoneal injections of asbestos fibers. After exposure to asbestos fibers, monocytes were recruited into the abdominal cavity and acquired the characteristics of inflammatory or nonspecifically activated macrophages. Nontoxic titanium dioxide or toxic silica particles did not produce activation of the free peritoneal macrophage population. Aggregates of asbestos fibers were found on the diaphragm and other peritoneal surfaces within only 24 h after a single injection. Macrophage recruitment to these sites peaked between 3 and 5 days, while activated macrophages persisted up to 14 days. Recruitment and activation of macrophages by repeated exposures to asbestos fibers may contribute to chronic damage of the mesothelial lining caused by these mineral fibers. PMID- 8216838 TI - Heterotransplantation of human Burkitt's lymphoma cell lines in athymic nude mice: tumor-host relationships. AB - We have explored the factors which influence tumorigenicity of Burkitt's lymphoma (BL) cell lines in athymic nude mice. Four cell lines, Namalwa, CA46, JD38, and ST486 revealed tumor incidence of 63.5, 69.0, 45.5 and 10.0%, respectively, in nude mice, but there was no correlation between tumor incidence and growth rate in vivo. Thus, growth rate and tumorigenicity are dependent upon different biochemical pathways. Evidence of tumor cell heterogeneity was demonstrated in the CA46 parent cell line. Five subclones derived from CA46 revealed varying degrees of tumor incidence (but very similar growth rates) that were consistently less than the parent CA46 line. Line 5, for example, produced 5.7-fold less tumors than the parent line. None of the BL cell lines or clones produced any metastatic lesions in liver, lung, brain, bone marrow or spleen in athymic nude mice. Northern blot analysis of c-myc mRNA levels in different BL cell lines revealed a possible relationship between percent tumor takes (but not growth rates) and the level of c-myc oncogene expression. However, no correlation was observed between c-myc mRNA levels and tumor incidence or growth rates among the CA46 clones. There was no correlation between the ability of the cell lines and the subclones to either secrete growth factors or to respond to growth factors secreted by Epstein-Barr virus-induced lymphoblastoid cells or lipopolysaccharide activated monocytes, and their growth rates or percent tumor takes in mice. Comparison of tumor incidence and growth rates in irradiated and unirradiated mice showed that host factors influenced the growth of BL in nude mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8216839 TI - Autografted minced muscle fragments do not affect muscle regeneration in partially excised rat gastrocnemius muscle. AB - The kinetics of the regeneration process following partial excision or mincing in the rat gastrocnemius muscle was compared using histological and physiological methods. Immediately following injury there was a marked decrease in the distance of shortening (DS) values during isotonic contraction, followed by a progressive increase until 2 weeks after injury. By 85 days the DS values attained those of control muscle during contraction against low loads (up to 50 g), and 80 and 62% of control values at 150 and 250 g, respectively. However, there was no difference in the DS values at 28 and 85 days after injury between muscles that were partially excised or when the removed part of the muscle was minced and placed in the injured site. It is concluded that the enrichment of an injured area of the gastrocnemius muscle with minced autografted muscle does not result in long-term improvement of the functional capacity of the regenerated muscle due to the addition of satellite cells and/or other factors in the minced tissue. PMID- 8216840 TI - Decreased immune reactivity and neuroendocrine alterations related to chronic stress in spinal cord injury and stroke patients. AB - Both natural and adaptive immune responses were found to be strikingly decreased 2 weeks after injury in 54 spinal cord injury and stroke patients, i.e., 28 quadriplegics, 21 paraplegics and 5 stroke patients, compared with those of age matched controls. All values are expressed as means. Natural-killer (NK)-cell function decreased to 21.0% 2 weeks after spinal cord injury compared with 48.6% in controls. At 2 weeks, plasma ACTH values increased to 17.0 pg/ml in patients compared with 11.2 pg/ml in controls, and urine free cortisol levels were elevated to 162.4 micrograms/24 h in patients compared with 53.6 micrograms/24 h in controls. T-cell function decreased to 40.2% of normal (lymphocyte transformation) by 3 months after injury. T-cell activation (IL-2R) was diminished, i.e., 183.4 micrograms/ml compared with 328.2 micrograms/ml in controls. With rehabilitation therapy, NK-cell function increased to 41.6% by 7 months after injury. NK-cell-mediated lysis diminished sharply between 7 and 9 months, decreasing to 22.8% at 10 months and ultimately returning to the level seen 2 weeks after injury. Rehabilitation therapy contributed to the restoration of T-cell function to 92.0% of normal by 6 months after injury where it remained for 6+ months. IL-2R values improved in parallel with lymphocyte transformation. Whereas NK-cell-induced lysis remained depressed, i.e., 11.8% at 6 months and 11.4% at 12+ months in patients not receiving therapy, the restoration of NK-cell function at 6 months to 40.6% in rehabilitated patients decreased to 23.0% with cessation of treatment. NK-cell-mediated lysis values in cervical injury patients were significantly less than those in the thoracic injury group. Functional independence measurement (FIM) scores of the two paralleled their NK-cell function. With rehabilitation therapy, NK-cell-mediated lysis in the cervical group increased from 15.2 to 28.4%, whereas it improved in the thoracic group with therapy from 26.8 to 43.7%. With rehabilitation therapy, lymphocyte transformation in the cervical group increased from 37.3 to 85.6% and improved in the thoracic group from 48.4 to 88.9%. With rehabilitation therapy, FIM scores improved from 49.7 to 74.0 in the cervical group and from 79.8 to 97.3 in thoracic patients compared with 126 in controls. NK-cell-mediated lysis was depressed to 28.9% in 5 stroke patients and improved to 38.0% following rehabilitation therapy. PMID- 8216841 TI - Expression and distribution of a human colon-carcinoma-associated antigen in normal and diseased liver tissue. AB - Expression and distribution of 17-1A, a human colon-carcinoma-associated antigen as defined by a monoclonal antibody (17-1A mAb), were evaluated in liver tissues from normal subjects and patients with inflammatory and noninflammatory liver diseases. The antigen recognized by 17-1A mAb is a 41-kD protein that does not belong to the proteins of the cytoskeleton. Using a streptavidin-biotin peroxidase method on frozen sections of liver tissue, it was located in the cytoplasm of bile duct epithelial cells in normal livers, whereas the hepatocytes were completely unreactive. When diseased liver tissue was examined, a strong 17 1A Ag expression was demonstrable in the epithelium of typical and atypical bile ductules in portal areas. In addition, periportal or periseptal hepatocytes revealed variable staining for 17-1A Ag directly related to acute and chronic inflammatory changes. 17-1A Ag expression in hepatocytes reached the highest frequency in acute hepatitis (5/5) and chronic active hepatitis (17/19). These results indicate that periportal hepatocytes are capable of acquiring antigen expression common to bile ductular cells in inflammatory liver diseases, further supporting the view that these ductules represent transformed hepatocytes. Furthermore, two distinct pictures were found in primary liver malignancies. Neoplastic bile duct epithelium did not maintain 17-1A Ag expression in cholangiocarcinoma, whereas neoplastic liver cells acquired cytoplasmic 17-1A Ag expression in clustered areas in hepatocellular carcinoma and the intensity of staining and antigen distribution were inversely related to the grade of tumor differentiation. PMID- 8216842 TI - Evaluation of oxidized low-density lipoprotein and large molecular size low density lipoproteins in atherosclerosis. AB - To study the roles of modified low-density lipoprotein (LDL) and the molecular size of LDL in atherogenesis, the following studies were carried out. Eight white male rabbits fed a standard oriental diet with 1% cholesterol were used to isolate LDL and to observe changes in the molecular size of LDL due to cholesterol feeding. The tissue LDLs in the aorta were analyzed to confirm the existence of modified LDL (namely, LDL with peroxidized cholesteryl ester) by thin-layer chromatography. In addition, plasma LDLs were isolated from 18 patients with myocardial infarction and 11 patients with angina pectoris to confirm the existence of LDL with peroxidized cholesteryl ester. Each LDL separated consisted of 3 fractions; namely, IDL (1.006-1.018), LDL1 (1.019-1.052) and LDL2 (1.053-1.063) by sequential ultracentrifugation. The molecular sizes of LDL were measured by a planimeter from electron microscopic photographs, with negative staining. The estimation of peroxidized cholesteryl linoleate in LDL was performed using our method. The modified LDLs with peroxidized cholesteryl ester were poorly estimated in the LDL separated from the plasma of cholesterol-fed rabbits and from the aorta extraction after 16 weeks of feeding. The peroxidized cholesteryl ester was clearly identified in the plasma LDLs of the patients with myocardial infarction and angina pectoris, and in whole extracts from human aortic atheroma, although it was not clearly identified in the tissue LDL fraction. The molecular sizes of LDL1 enlarged week by week with cholesterol feeding, but two fractions of IDL and LDL2 did not change in size. The infusion of cholesterol-rich LDL of large molecular size or LDL with peroxidized cholesteryl ester into the vessels led to fixation, on the surface of the arteries of many platelets, red cells, and white cells, and to marked irregularities in the endothelial folds. The evidence suggests that atheromas, formed in a short period in rabbits with cholesterol feeding, are caused mainly by the increase in LDL1 of large molecular size, and that foam cells, formed in human atheromas, are caused mainly by the production of modified LDL with peroxidized cholesteryl ester. PMID- 8216843 TI - Erythropoietin does not cross the placenta into the fetus. AB - Erythropoiesis in the fetus is controlled by erythropoietin (Ep). To determine the role of maternal Ep in this process, we used catheterized preparations of sheep and monkey fetuses to assess the ability of Ep administered to the mother to cross the placental barrier into the fetus. Ep was injected into pregnant sheep (3,600 IU/sheep) or monkeys (800-2,000 IU/animal) as a single intravenous dose, or into sheep in intravenous doses of 2,000 IU once every 12 h for a total of 4 injections. Maternal and fetal blood samples for Ep and reticulocyte determinations were obtained before and at intervals after Ep injections. The administration of Ep resulted in significant increases in maternal circulating Ep levels in sheep and monkeys. Despite the presence of high levels of maternal Ep, however, no increase in fetal plasma Ep levels was detected. The administration of Ep to the mother caused significant increases in reticulocyte production in the mother but not the fetus; injection of Ep directly to the fetus stimulated fetal erythropoiesis. These results demonstrate that Ep does not cross the placenta into the fetus even under conditions of chronically elevated maternal Ep levels, and suggest that red cell production in the fetus is regulated by Ep produced from sites within the fetus. PMID- 8216844 TI - Effect of lithium in murine immunodeficiency virus infected animals. AB - Murine AIDS (MAIDS) is a disease that shows many similarities to human HIV infection. The etiological agent of MAIDS is a defective murine leukemia virus that seems to be able to induce disease in the absence of viral replication. This animal model has been useful in stimulating the search of answers to questions and the formation of new hypotheses related to human AIDS. The monovalent cation lithium can influence a number of immunohematopoietic cell types and cellular processes where proliferation and differentiation occur. We describe here the result of in vivo studies investigating the effect of lithium treatment on MAIDS infected mice. Viral control and lithium-treated animals were monitored for survival and development of MAIDS pathology. MAIDS animals treated with lithium demonstrated a marked reduction in their development of lymphadenopathy and splenomegaly. Both MAIDS control and lithium-treated virus-infected mice developed evidence of lymphoma; however, the involvement was much more massive both at the gross and microscopic levels in the MAIDS control compared with the lithium-treated mice. These data suggest that lithium may be effective in modulating murine immunodeficiency virus infection and raise important questions related to the potential role lithium may play in the pathophysiological processes associated with retroviral infections. PMID- 8216845 TI - Theoretical analysis of cotransport: its use in alanine uptake in plasma membrane vesicles. AB - A theoretical model of a cotransport system in plasma membrane vesicles has been utilized for the analysis of the Na(+)-dependent L-alanine transport into plasma membrane vesicles purified from Yoshida ascites hepatoma (AH 130) cells in the exponential and stationary phases of growth. The analysis was performed by comparing the experimental curves with computer simulations. In particular we considered the differences in alanine uptake observed in the two preparations and we tried to ascribe them to changes of some parameters of the transport model. The simulations indicate that sodium, alanine or water passive permeability changes cannot explain the experimental data which are consistent, on the contrary, with a relevant enhancement of the Vmax of the transport agency. The involvement of the membrane electrical potential difference is also discussed. PMID- 8216846 TI - Inhibitory role of alveolar macrophages in colony-stimulating factor production by the lung tissue from bacillus Calmette-Guerin-treated animals. AB - Production of colony-stimulating factors (CSF) by lung tissue from rats injected by bacillus Calmette-Guerin (BCG) and the role of alveolar macrophages (AM) in this process was studied. Injection of BCG at 10, 100, or 1,000 mg/kg changed the CSF production by the lung in a time-dependent manner. Maximum stimulation was observed at 10 mg/kg and 3 days of interval between BCG injection and animal sacrifice. Longer periods or higher concentrations had no effect or actually depressed CSF production. BCG injection also changed the number of AM in a time- and dose-dependent manner. When AM from BCG-treated animals were lavaged out and the AM-depleted lung tissues were cultured, an increase in CSF production with respect to controls was observed at 10 mg/kg of BCG. On the other hand, in control animals removal of AM had no effect on CSF production by the lung. The results suggest that BCG treatment alters the number of AM and CSF production by the lung. AM, in BCG-injected animals, inhibit CSF production by the lung tissue while in non-injected animals they do not play any role in this process. PMID- 8216847 TI - Antigen presentation by a continuous human microvascular endothelial cell line, HMEC-1, to human T cells. AB - Endothelial cells line the vessels and lymphatics of the body, acting as a barrier between the blood and extravascular tissue. These cells are, therefore, in a prime position to play a role in lymphocyte activation. Indeed, it has been shown that primary endothelial cells in culture are capable of presenting particulate and soluble antigens to T cells and that this response is not dependent on macrophages. Recently, we developed an immortalized line of human microvascular endothelial cells, CDC/EU.HMEC-1 (HMEC-1). This endothelial line has the advantage not only of being devoid of contaminating cells but also of being a continuous cell line and therefore not subject to a restricted number of useful passages. The focus of this study was to determine whether HMEC-1 cells (like primary endothelial cells) could present antigen to T cells in the absence of macrophages. We demonstrate that a cloned and purified endothelial cell line can independently provide all the necessary signals for antigen-specific T-cell activation. PMID- 8216848 TI - Heterologous and homologous protection against influenza A by DNA vaccination: optimization of DNA vectors. AB - We have recently shown that direct injection of DNA can be an effective vaccine strategy eliciting both humoral and cell-mediated immune responses. Vectors were designed specifically for vaccination by direct DNA injection and refined to improve plasmid production in Escherichia coli. The vectors consist of a pUC-19 backbone with the cytomegalovirus (CMV) IE1 enhancer, promoter, and intron A transcription regulatory elements and the BGH polyadenylation sequences driving the expression of the reporter gene CAT or influenza A nucleoprotein (NP) or hemagglutinin (HA). The respective vectors expressed high levels of chloramphenicol acetyltransferase (CAT) and NP in tissue culture, and yielded 14 15 mg of purified plasmid per liter of Escherichia coli culture. Immunization of mice with the NP and HA expression vectors resulted in protection from subsequent lethal challenges of influenza using either heterologous or homologous strains, respectively. PMID- 8216849 TI - Use of DNA encoding influenza hemagglutinin as an avian influenza vaccine. AB - Recently, we demonstrated that direct inoculation of a hemagglutinin 7 (H7) expressing DNA could vaccinate chickens against a lethal H7 influenza virus challenge. These experiments used a defective-retroviral-based vector to express H7 (p188) (Robinson et al., 1993). Here, we report protective immunizations using a non-retroviral-based vector for H7 expression (pCMV/H7). Unlike the previously used retroviral-based vector, this vector cannot be transmitted as an infectious agent (as a consequence of phenotypic mixing with exogenous or endogenous virus proteins). Vaccination was accomplished by inoculating young, immunocompetent chickens by each of three routes (intravenous, intraperitoneal, and intramuscular) with 100 micrograms of cesium chloride-purified pCMV/H7 DNA in saline. After two immunizations, birds were challenged via the nares with a lethal dose of a highly virulent chicken influenza virus of the H7 subtype. The results of five independent vaccine trials demonstrated protective immunizations in approximately 60% of the pCMV/H7 DNA-inoculated chickens. By contrast, only 3% of the chickens inoculated with control DNA survived the lethal challenge. PMID- 8216850 TI - Examination of parameters affecting the elicitation of humoral immune responses by particle bombardment-mediated genetic immunization. AB - A human growth hormone expression construct was delivered intracellularly into the abdominal skin of mice by particle bombardment-mediated gene transfer. Using this technology, the in vivo delivery of antigen-encoding expression vectors affixed to gold microprojectiles results in de novo antigen production in target skin and development of specific antibody responses. In this study, we examined the contribution of various delivery parameters to the resultant protein expression and related antibody responses. The highest levels of both protein expression and antibody production were correlated with particle delivery to the epidermis while deliveries extending into the dermis resulted in decreased protein and antibody production. Optimal immune responses were also shown to be dependent upon the delivery of a sufficient number of DNA-coated gold particles, indicating that a dose-response relationship exists between the number of particles delivered and the resultant protein expression and antibody production. Further, maximal protein expression and associated antibody titers were elicited with surprisingly small amounts of DNA. The practicality of targeting skin and the use of three to four orders of magnitude less DNA than is typically required in direct DNA inoculation studies demonstrates the potential utility of this emerging technology for the rapid production of antibodies in laboratory animals, and in the development of a new class of human clinical vaccines based upon direct, intracellular DNA delivery. PMID- 8216851 TI - DNA inoculation induces neutralizing immune responses against human immunodeficiency virus type 1 in mice and nonhuman primates. AB - DNA, or genetic, inoculation mimics aspects of attenuated vaccines in that synthesis of specific foreign proteins is accomplished in the host. These proteins can be processed and presented on the relevant major histocompatibility complex (MHC) antigens and ultimately become the subject of immune surveillance. Very recently, we have described the use of the new technology to generate immune responses in mice against the human immunodeficiency virus type 1 (HIV-1) envelope using a gp160 DNA construct. Further analysis of this technology specifically in regard to HIV vaccine design is clearly important. In this report, we describe the analysis of additional HIV constructs as immunogens in both mice and report the use of this genetic immunization technology in nonhuman primates. In these studies, successful seroconversion occurs in more than 70% of the mice following the second immunization with 100 micrograms of construct DNA; three and four immunizations result in routinely 100% seroconversion of the mice. Furthermore, the same strategy has successfully seroconverted primates following their second inoculation, resulting in the generation of both antiviral and neutralizing antibodies in this animal species. These studies are the first report of which we are aware that demonstrate successful immunization of nonhuman primates through genetic vaccination technology and the first to describe genetic immunization of primates against HIV antigens. This technology has relevance for the development of safe and efficacious immunization strategies against HIV because it provides for relevant antigen production in vivo without the use of infectious agents. PMID- 8216852 TI - Identification of genomic sequences that mediate the induction of the endoplasmic reticulum stress protein, ERp72, by protein traffic. AB - ERp72, a resident protein of the endoplasmic reticulum (ER) is both a stress protein and a member of the protein disulfide isomerase family of proteins. Analysis of the murine ERp72 promoter region revealed the presence of potential transcriptional control elements characteristic of the promoters of mammalian ER proteins. These include multiple CCAAT elements and Sp1 and AP-2 consensus sequences. Functional analysis of mutations in the ERp72 promoter and 5'-flanking region revealed an 82-bp fragment that is sufficient to mediate the stimulation observed for ERp72 either by stress or by the expression of incompletely assembled immunoglobulin mu heavy chain in the ER. This 82-bp fragment contains two CCAAT elements but little additional homology to protein traffic-responsive sequences of other members of the ER stress family. This suggests that the ERp72 gene contains a novel element that is the target of an intracellular signaling pathway initiated by protein traffic in the ER. PMID- 8216853 TI - Changes in cellular proteins associated with the expression of human immunodeficiency virus type 1 trans-activator protein Tat. AB - Earlier studies have revealed a distinct class of regulatory proteins known as trans-activator proteins in diverse biological systems. These proteins have been shown to act on both homologous and heterologous promoter targets. Activation of heterologous targets is speculated to be an integral part of virus-induced pathogenesis. To verify this hypothesis, stable Tat-producing human rhabdomyosarcoma (RD) cell lines were generated. These cell lines produced significant levels of functional Tat, as measured by transfection with the reporter plasmid pLTR-CAT. Tat-producing cells, although morphologically similar to the control, exhibited a slower growth rate. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the cellular proteins from control (tat-) and tat+ cells revealed increased quantities of 34- and 40-kD proteins along with the appearance of a new 74-kD protein in tat+ cells. Subsequent two-dimensional gel analysis revealed several additional differences. Tat+ cell lines produced two proteins of M(r) 19.5 and 44 kD anew, while proteins with M(r) 14.5, 42, and 52.5 kD were in greater abundance. Interestingly, a 26-kD protein that was originally present in the G418+/tat- (control) sample disappeared in the presence of Tat. These data support a possible modulator role for Tat in cellular gene expression. PMID- 8216854 TI - The gene for C10, a member of the beta-chemokine family, is located on mouse chromosome 11 and contains a novel second exon not found in other chemokines. AB - C10 is a recently described member of the beta-chemokine subfamily of the chemokine superfamily of cytokine proteins. Genomic clones encoding murine C10 were isolated and sequenced. The other members of the beta-chemokine family have a three-exon genomic structure containing, among other sequence similarities, four cysteines spaced in a highly conserved manner. In each of these genes, the second exon contains the first three of the four conserved cysteines, and the third exon contains the last. In contrast to this genomic structure, the C10 gene has four exons, with a novel second exon of 48 nucleotides. Exons 3 and 4 of C10 contain four cysteines distributed in the same manner as in exons 2 and 3 of other beta-chemokine family members. The novel second exon codes for a large number of charged amino acids, and this exon shows no homology to any previously described sequences in computer databases. Linkage studies showed that the C10 gene (Scya6) is closely linked to the Scya2 locus on mouse chromosome 11, indicating that the C10 gene is located in the same region of mouse chromosome 11 as other members of the beta-chemokine family. Thus, although the C10 gene contains a novel exon not found in any other members of the chemokine superfamily, its chromosomal location and conservation of cysteine residues and other structural features suggest that it evolved from the same ancestral gene as other members of the beta-chemokine family. PMID- 8216855 TI - Differential regulation of the CYP11A1 (P450scc) and ferredoxin genes in adrenal and placental cells. AB - The regulation of the genes encoding cholesterol side-chain cleavage enzyme (P450scc) and ferredoxin, two components in the first step of steroid synthetic pathways, was studied by RNA analyses of endogenous and transfected genes. cAMP rather than calcium was the major secondary messenger that stimulated expression of both P450scc and ferredoxin genes in human placental JEG-3 cells. The effect of cAMP on P450scc expression was abolished by cycloheximide in JEG-3 cells, but it was superinduced in mouse adrenal Y1 cells. For ferredoxin expression, both reagents have synergistic effect in Y1 and JEG-3 cells. To test the mechanism of regulation, DNA segments containing regulatory elements of the P450scc and ferredoxin genes were connected to reporter genes and analyzed in cotransfection experiments. The results showed that the proximal cAMP-responsive sequences of both P450scc and ferredoxin genes were stimulated by cAMP early in both Y1 and JEG-3 cells, requiring no new protein synthesis. This indicates a common mechanism for the regulated expression of both genes. P450scc possessed an additional upstream cAMP-responsive sequence that also responded to cAMP induction in a different manner from the proximal element. The presence of additional upstream regulatory elements makes it possible for the P450scc gene to be further regulated. PMID- 8216856 TI - [Development and current aspects of occupational health in Brazil]. AB - The main objective of this study is to describe and analyze the health situation of workers in Brazil in the 1980s, as a process with technical, political, socioeconomic, and cultural dimensions. The main sources of data and information were: the Brazilian Institute of Geography and Statistics (IBGE), the National Institute of Social Security (INSS), and international agencies like the International Labor Office (ILO), the World Health Organization (WHO), and available specialized literature. The severity of the workers' patterns of morbidity and mortality emerges from this analysis, as well as the inadequacy of the public policies implemented by the State to deal with these issues and find efficient solutions. The study also points out the importance of the social process that occurred in this decade, with the participation of workers and health professionals, which was responsible for important achievements, particularly in the field of legislation. In conclusion, some issues and challenges for further improvement of the workers' quality of life, through the improvement of health and working conditions, are presented. PMID- 8216857 TI - [Patient-oriented care. Form and content]. PMID- 8216858 TI - [Patient-oriented care. 'Even after its introduction you must continue to think'. Interview by Toine de Graaf]. PMID- 8216859 TI - [Patient-oriented care. The participative model]. PMID- 8216860 TI - [Patient-oriented care. The top-down approach]. PMID- 8216861 TI - [Introduction of a rehabilitation-oriented nursing system]. PMID- 8216863 TI - [Patient-oriented care. 'It is a cultural change']. PMID- 8216862 TI - [Introduction of patient-oriented care. An evaluation study in 4 hospitals]. PMID- 8216864 TI - [A study of quality care in pediatric departments]. PMID- 8216865 TI - [Resident-oriented nursing models in nursing homes]. PMID- 8216866 TI - [Patient-oriented care. 'Many supervisors dare give too little guidance'. Interview by Toine de Graaf]. PMID- 8216867 TI - [Fiftieth anniversary of the Health Secretariat]. PMID- 8216868 TI - [Outbreak of respiratory syncytial virus at a neonatal intensive care unit in Mexico City]. AB - RSV can be spread in hospital wards, being thus responsible for increased morbidity and mortality among infected patients. We describe an RSV outbreak in a Neonatal Intensive Care Unit (NICU). METHODS. As soon as the first RSV cases were detected in the NICU, every patient, as well as the personnel taking care of them, were tested; nasal washes for viral isolation, and nasopharyngeal swabs for viral antigen detection by immunofluorescence, were collected. RESULTS. Twelve patients were hospitalized. RSV was detected in eight, coinfection was observed in three of them. RSV was also detected in three adults. We describe the clinical findings among the RSV infected patients, and the infection control measures that we followed to stop the RSV spread. CONCLUSIONS. Viruses can be responsible for nosocomial infections, being thus mandatory to establish the diagnosis, treatment and infection control measures. In our NICU, the RSV infected patients had mild to moderate disease, there were no deaths attributable to RSV infection. We discuss infection control measures. PMID- 8216869 TI - [Juvenile dermatomyositis: clinical, immunologic, and therapeutic characteristics]. AB - Although dermatomyositis is a rare disease in infancy, it involves several systems and tissues throughout the body causing death or serious disabilities at the musculoesquelethal level. The increased incidence of vasculitis and other characteristics in children make their clinical presentation different from the adult, which could modify the diagnostic criteria, course disease and treatment of the child. We analyze the clinical experience at Hospital Infantil de Mexico Federico Gomez with 21 children studied during a period of ten years. All patients fulfilled the Bohan and Peters diagnostic criteria and 91% of them responded to treatment. At the present time 52% are in remission without treatment, 37.7% improved with treatment, 4.5% with little response to treatment and 4.7% have died because of infections. PMID- 8216870 TI - [Evidence of genetic and environmental factors in manual laterality. Study of 120 Mexican families]. AB - Environmental factors as well as different modes of inheritance has been suggested to explain the etiology of left-handedness. In order to improve knowledge of this problem, manual skill (MS) of parents (n = 234), siblings (n = 506) and children (n = 126) of 60 right-handed (RHI) and 60 left-handed (LHI) index cases (IC), born in Mexico City, were studied. Parents and siblings of both IC had similar frequencies of left-handedness. Quite the contrary, 36.7% of children of LHI were left-handed, while 7.3% children of RHI happen to be left handed (P < 0.00025). No differences were found in the appearance of perinatal environmental factors. These findings are explained in part according to the pressure exerted by parents and/or teachers for dextrality. The impact of this influence modifies the effect of several unknown genes (multifactorial inheritance). The understanding of the above mechanisms in the etiology of MS is relevant not only for academic purposes, but for the educational sphere as well. PMID- 8216871 TI - [Iron storage in infants at 2 and 8 months of age]. AB - For to establish the probability of the early identification of the iron deficient in the infant, we evaluate the correlation between the serum ferritin (SF) values at two and eight months of age. It included 57 infants, 30 cases with SF higher than 20 ng/mL (group I), eight cases with SF between 12-20 ng/mL (group II) and 19 infants with SF lower of 12 ng/mL (group III); the addition of two late groups result in 27 cases with SF lower of 20 ng/mL (group IV). None cases had SF lower 20 ng/mL at two months of age. The correlation between SF values and hemoglobin (Hb) at two and eight months of age, the Hb of the infants deficients had better correlation (0.602 P = 0.006). The SF not had statistic correlation. For to establish if the groups had the same values of SF and Hb at two months on age, the SF values were in the group III vs group I were 154.1 and 274.6 ng/mL (P = 0.004) respectively. This data indicate that the infants that development severe iron deficiency to eight months of age, may predict this quantify the SF at two months of age. PMID- 8216872 TI - [Correlation between serotype and electrophoretype of rotaviruses isolated in 2 Mexican populations]. AB - In order to study the correlation between the serotype specificity and the genomic RNA electrophoretic pattern (electropherotype) of human rotavirus (HRV) strains, we analyzed the electropherotypes of 54 HRV that had been collected during a four year study in Mexico, and whose serotypes had been previously determined. We detected 17 different electropherotypes, four in association with serotype G1, two with serotype G2, six with serotype G3, and five with serotype G4. There were no viruses with the same electropherotype having a different serotype. The variations in RNA electrophoretic migration were greater between viruses belonging to different serotypes than between viruses of the same serotype. It is of note that the relative separation of RNA segments 7 and 9 remained constant among viruses of the same serotype. Electropherotyping might have a serotype predictive value for rotavirus specimens lacking the virion outer capsid. PMID- 8216873 TI - [Posterior perineal hernia. Report of a case and review of the literature]. AB - We report a case of a seven months old female patient with diagnosis of generalized primary elastosis or cutis laxa, that also presented a posterior perineal hernia; it was treated with surgery (abdominal and perineal) and the postoperatory evolution was favorable. In the literature it had been reported around 100 cases of posterior perineal hernia; but most of them occurred in adults patients of the female sex, with a high proportion of pregnancy or as a result of radical cancer surgery like pelvic exenteration. This is the first case of posterior perineal hernia in the Hospital Infantil de Mexico Federico Gomez and the third founded in pediatric age in the literature. PMID- 8216874 TI - [Malignant fibrous histiocytoma of the orbit as second tumor in a case of bilateral retinoblastoma]. AB - The case of a 30 months-old child with malignant fibrous histiocytoma of the left orbit diagnosed 18 months after treatment with external beam radiotherapy for bilateral retinoblastoma is presented. The clinical and histological characteristics of malignant fibrous histiocytoma and its relation as a second malignant tumor in patients affected with retinoblastoma are analyzed. PMID- 8216875 TI - [Esophageal perforation in premature newborn infants. Presentation of 8 cases]. AB - We report eight newborn with esophageal perforation. They were preterm infants and received mechanical ventilation for respiratory problem. Six were associated with pneumothorax, three of they show aberrant way of an orogastric tube, and another three show milk fluid in the pleural tube installed for pneumothorax. The management was fasting during ten days, parenteral nutrition, wide spectrum antibiotics, and prevention of complications; surgery treatment is not the first of all recommended at present. PMID- 8216876 TI - [Liaison psychiatry at a neonatal intensive care unit. Interphase between psychiatry of the infant and neonatology]. AB - A description is made of the situation of neonates and their families during hospitalization in the Neonatal Intensive Care Unit (NICU). Emphasis is made on the stressful situations faced by the infants, the families and the caregivers as well as on potential interventions to ameliorate their negative impact and to promote a favorable outcome. With the infants, the situation is one of overwhelming aversive stimulation, noncontingent responses and painful procedures, coupled with deprivation of normative experiences, propiciated by their illness and the structure of the unit. With the families, their feelings of impotence, guilt, and separation from their infant are highlighted, and interventions are described that may help them in this situation of crisis. With the staff the intervention consists on education and sensitization to the infant's needs. The liaison psychiatrist is the infant's voices with the families and the staff. The literature is reviewed in terms of the potential effects of favorable stimulation and of the negative experiences of neonates while at the NICU. PMID- 8216877 TI - Alcohol effects on the immune system: Third Annual Meeting of the Alcohol and Drug Abuse Immunology Symposium, Vail, Colorado, March 25-29, 1993. Abstracts. PMID- 8216878 TI - Blood count and hematologic morphology in nonanemic macrocytosis: differences between alcohol abuse and pernicious anemia. AB - In order to find out if blood count parameters could help to differentiate between the two most common causes for nonanemic macrocytosis, alcohol abuse and vitamin B12 deficiency, we studied 18 nonanemic pernicious anemia patients and 136 alcohol abusers without deficiency of folate and with an erythrocyte mean cell volume (MCV) value > or = 100 femtoliters. In addition to blood count reticulocytes, peripheral blood smear and marrow aspirates were examined. The combination of a low red cell count (< 4.0 x 10(12)/l) or a high red cell distribution width (E-CDW) value (> 15.0%) with a normal thrombocyte count and a normal thrombocyte mean cell volume (T-MCV) was found in 94.4% of the vitamin deficient patients but in only 14.6% of the abusers, in 25.0% of the folate deficient patients (n = 8), and in 26.9% of the patients without any cause for macrocytosis (n = 52). None of the peripheral blood smear or marrow findings exceeded this sensitivity, and the few highly specific findings had low sensitivities. Thus, the combination of the four blood count parameters proved to be, as compared to hematologic morphology, a good diagnostic tool in selecting patients for appropriate further diagnostic tests. All patients with macrocytosis should be asked about their alcohol consumption. Additionally, serum B12 vitamin should be measured at least when nonanemic macrocytosis is combined to a low red cell count or a high E-CDW and the thrombocyte count and T-MCV are normal. PMID- 8216879 TI - Event-related potentials in women at risk for alcoholism. AB - Event-related potentials (ERPs) elicited during information processing tasks are useful for assessing brain function. Abstinent male alcoholics exhibit deficits in ERPs. The present study found that female alcoholics with early onset alcoholism (18.3 +/- 1.3 years) showed significant deficits in P300 amplitude relative to both high-risk and low-risk controls. Two interpretations of these findings are possible. P300 amplitude reduction among the alcoholic women might be a neuropathological consequence of excessive drinking. Alternatively, lower amplitude of the P300 wave may be a marker for alcoholism risk segregating within high-risk families and associated with development of alcoholism. The later interpretation is favored based on the unlikely possibility that the nonalcoholic high-risk women would later convert to alcoholic status due to their age (mean age of 35.6 +/- 1.6 years). PMID- 8216880 TI - Lead/ethanol interactions. I: rate-depressant effects. AB - Adult male rats were exposed to a diet containing 500 ppm added lead as lead acetate (group lead-diet) or a control diet containing no added chemicals (group control-diet) for 61 days prior to commencing fixed-ratio 32 (FR 32) lever press training for water reinforcement. After steady state responding was achieved, all animals received serial administrations of acute doses of ethanol prior to the daily training session. Specifically, lead-diet and control-diet rats received i.p. injections of .25, .5, .75, 1.0, and 1.25 g/kg ethanol, in ascending order, alternating daily with injections of saline. The results revealed a dose dependent rate-depressant effect, with higher doses of ethanol producing more behavioral suppression than lower doses for both groups. In addition, at the dose of 1.0 g/kg it was observed that the suppressive effects of ethanol on schedule controlled responding were reduced among lead-treated animals relative to controls. These data are discussed in terms of lead-induced attenuation of the pharmacologic effects of ethanol. PMID- 8216881 TI - Lead/ethanol interactions. II: pharmacokinetics. AB - Adult male rats were exposed ad libitum to water containing either 500 ppm lead acetate (group-lead) or an equivalent amount of sodium acetate (group-control) for 60 days prior to receiving ip injections of either 1.0, 2.0, or 3.0 g/kg ethanol (20% v/v). Blood alcohol concentrations (BACs) were recorded over a 6-h time period postinjection, and the groups were compared at each dose for differences in the pattern of ethanol pharmacokinetics. While there was a dose related effect obtained with increasing ethanol doses producing increasing BAC values, at no dose was there any evidence of group separation at any point during the 6-h postinjection period. These data are instructive with respect to understanding the nature of previously demonstrated lead/ethanol interactions, and rule out the possibility that lead-induced disturbances in the catalysis of ethanol, or some other pharmacokinetic operation, is the basis for the effects of lead on ethanol intake and ethanol administration. Alternative possible accounts of this curious interaction between a xenobiotic contaminant and alcohol are discussed. PMID- 8216882 TI - The abilities of 5-HT3 receptor antagonist ICS 205-930 to inhibit alcohol preference and withdrawal seizures in rats. AB - Recent evidence suggests that central 5-HT3 are intimately involved in the ethanol (ETOH) dependence mechanism. In the present study we observed the effects of the 5-HT3 receptor antagonist ICS 205-930 on audiogenic seizure response (ASR) in ETOH-withdrawn rats and on ETOH intake and preference. Low doses of ICS 205 930 (0.001 mg/kg), but not higher doses (0.1 mg/kg), markedly reduced both ASR and ETOH intake in a high preference group of animals. The possible mechanism of different effects of low and high drug doses is discussed. PMID- 8216883 TI - Sex-related differences of plasminogen activator activity and plasminogen activator inhibition in the gastric wall after chronic ethanol consumption: effect of orchidectomy or ovariectomy. AB - Plasminogen activator activity (PAA), tissue-type PA (t-PA) antigen level, plasminogen activator inhibition (PAI), and plasmin inhibition (PI) showed no sex dependent differences in the stomach of the rat. Chronic ethanol consumption induced an increase of PAA and t-PA antigen and a decrease of PAI (urokinase-type PA [u-PAI]) and PI in the body and pyloric region (PI only in the pyloric region). PAA increase and u-PAI decrease in the pyloric region were greater in the male than in the female. Orchidectomy, but not ovariectomy, induced effects similar to those of ethanol. The effects of orchidectomy and chronic ethanol consumption on gastric PAA, t-PA antigen, and PAI were additive. An increased PAA and decreased PAI or PI in the stomach in cases of hypogonadism, particularly if this deficiency is combined with chronic ethanol consumption, might influence the susceptibility to pathological conditions related to or affected by the local fibrinolytic activity (PAA, PAI, or PI). PMID- 8216884 TI - Effect of diet and disulfiram on acetaldehyde blood levels after ethanol in UChA and UChB rats. AB - Acetaldehyde (AcH) levels in blood samples taken from different zones of the vascular system 2 h after a p.o. dose of ethanol (2.76 g/kg) were studied in UChA (low ethanol consumer) and UChB (high ethanol consumer) rats fed a diet devoid of animal products, diet 1 (D1), and a diet containing fish meal, diet 2 (D2), and in rats pretreated with disulfiram (600 mg/kg p.o.). The results showed that, while there is no significant difference between UChA and UChB rats fed D1 with respect to blood AcH levels and the basal activity of the hepatic mitochondrial high-affinity aldehyde dehydrogenase (AIDH), a significant strain difference was observed in rats fed D2, which induced high blood AcH levels in UChA rats but not in UChB ones. No strain differences were observed in blood ethanol levels in the two groups of rats. When rats fed D1 were pretreated with disulfiram, the raising of AcH blood levels induced by ethanol after disulfiram was significantly higher in UChA than in UChB rats in suprahepatic vein, femoral vein, and tail blood. This difference was concomitant with a greater inhibition of the hepatic mitochondrial high-affinity ADH activity in UChA rats than in UChB ones, whether disulfiram was administered in vivo or in vitro, which excluded the possibility that the strain difference would be caused by a different bioavailability of disulfiram. PMID- 8216885 TI - Densities of dopamine D2 receptors are reduced in CNS regions of alcohol preferring P rats. AB - The densities of dopamine D2 recognition sites labelled with [3H]sulpiride were determined in the caudate-putamen, nucleus accumbens (medial and lateral portions), olfactory tubercle, substantia nigra (pars reticulata and pars compacta), and ventral tegmental area (VTA) of alcohol-naive, selectively bred P (N = 7) and NP (N = 7) rats using quantitative autoradiography. The binding of [3H]sulpiride was 20-25% lower (P < 0.05) in the caudate-putamen, medial and lateral nucleus accumbens, and VTA of the P compared with the NP rats. No significant differences were observed between the P and NP rats in the olfactory tubercle or substantia nigra. [3H]Sulpiride binding, using standard membrane preparations, established with Scatchard analysis that the difference in the densities of D2 recognition sites in the caudate-putamen between the P and NP rats was due to lower Bmax values for the P line. The results indicate that the number of dopamine D2 receptor sites is lower in several central nervous system regions of the P rats compared to NP rats. PMID- 8216886 TI - Brain MAP-2 phosphorylation is decreased following prenatal alcohol exposure in rats. AB - The effects of prenatal alcohol treatment on the development and in vitro phosphorylation of specific neuronal phosphoproteins isolated from the frontal cortex and hippocampus of rat brains were studied. In vitro phosphorylation of microtubule-associated protein-2 (MAP-2) was decreased in the frontal cortex but not the hippocampus of animals exposed prenatally to alcohol. Phosphorylation of additional phosphoproteins, including tau proteins, Synapsin I, and GAP-43, was not affected by prenatal alcohol exposure. Littermates of animals used for the phosphorylation assays showed impaired passive avoidance learning. These data demonstrate that the previously reported structural changes in the development of the cerebral cortex following prenatal alcohol exposure and behavioral deficits are accompanied by changes in the phosphorylation of the important cytoskeletal protein MAP-2. PMID- 8216887 TI - Influence of long-term ethanol treatment on rat liver biotransformation enzymes. AB - The influence of rats' long-term ethanol consumption on liver enzymes that could be involved in the biotransformation of benzo(a)pyrene [B(a)P] has been studied. Male and female Wistar rats received an increasing amount of ethanol in their drinking water up to 15% (w/v) in three weeks. The ethanol content was kept at a concentration of 15% for another three weeks. One group of rats also received B(a)P in the last week of the ethanol treatment. Livers were isolated, and microsomal and cytosolic fractions were prepared. In every enzyme measurement sex differences were observed. Long-term ethanol consumption induced P450, especially aniline 4-hydroxylase (P4502E1). However, testosterone 6 beta-hydroxylase (P4503A2 and P4502C13) in males and testosterone 12 beta-hydroxylase in females were decreased. The phase 2 enzymes glutathione S-transferase (subunit 1) and epoxide hydrolase were also decreased in their activity. Our results support the hypothesis that the effect of long-term ethanol consumption on B(a)P biotransformation as found in in vivo and in vitro studies, consisting of lowered formation of phenolic and diolic metabolites, is the result of a decrease of constitutive P450 isoenzymes. PMID- 8216888 TI - Effects of prenatal alcohol exposure on the developmental pattern of temperature preference in a thermocline. AB - Prenatal alcohol exposure is associated with a variety of impairments in neonatal state regulatory systems. Since prenatal alcohol exposure causes thermoregulatory deficits in response to both heat and cold stress in rats, body temperature set point might be altered in alcohol-exposed offspring. The effect of prenatal alcohol exposure on behavior in a thermocline was investigated in 10-, 15-, and 125-day-old male and female rats from three prenatal treatment conditions: alcohol liquid diet, pair-fed liquid diet control, or standard control. Subjects were placed in the thermocline in the cold, hot, or middle start positions and observed for 60 min. Subjects exposed to alcohol prenatally had a wider "preference zone" than control subjects at 10 and 15 days of age, but did not as adults. This widening of the temperature set-point in young subjects prenatally exposed to alcohol may represent a developmental lag in the development of body temperature set-point or a central compensatory process allowing the animal to adapt to alternating experiences of heat and cold stress. PMID- 8216889 TI - Studies of whole blood-associated acetaldehyde levels in teetotalers. AB - We measured whole blood-associated acetaldehyde (WBAA) levels in 225 teetotalers (123 females, 102 males) between the ages of 18 and 86 years. Values were normally distributed, but mean values for females were significantly lower than for males (7.6 +/- 0.6 vs. 7.9 +/- 0.7 microM, p < 0.0001). There was a significant positive correlation with age for the entire group (r2 = 0.149, p = 0.001) and for both sexes. The correlation with WBAA and age was stronger for females. Significant but lesser positive correlations were found between WBAA and other variables that increase with age, including glucose, fructosamine, cholesterol, alkaline phosphatase, serum glutamate pyruvate transaminase (SGPT), gamma glutamyl transpeptidase (GGT), and creatinine in the entire data set. Partial r analyses indicated that the correlations were mediated through the primary association of WBAA and age. We conclude that in individuals who do not consume ethanol there are significant sex differences in whole blood acetaldehyde and that the values increase throughout life. PMID- 8216890 TI - Ethanol sensitivity and consumption in F2 hybrid crosses of ANT and AT rats. AB - ANT rats that are highly sensitive to the motor-impairing effects of moderate ethanol doses voluntarily drink less ethanol in a free-choice test between 10% (v/v) ethanol solution and water than the ethanol-insensitive AT rats, suggesting the possibility that ethanol drinking is affected by initial ethanol sensitivity. However, in the F2 hybrid crosses of ANT and AT rats, voluntary ethanol drinking did not correlate with sensitivity to the motor-impairing effects of ethanol in the tilting plane test. Therefore, initial ethanol sensitivity does not appear to be a major factor in explaining variation in voluntary ethanol drinking. PMID- 8216891 TI - Reduction in the level of immobilization in forced swim test and ethanol intake in rats by oxygen therapy. AB - Experiments replicated the previous finding that rats with high immobilization time in the forced swim test (passive rats) consumed more 15% ethanol solution in a free choice situation with tap water than rats with active behavior (active rats). Exposure of passive rats to oxygen under normal and elevated (2 ata) pressure resulted in the decrease in immobilization scores in the forced swim test as well as reduction in alcohol consumption and preference. PMID- 8216892 TI - Identification of porcine oocyte 55 kDa alpha and beta proteins within the zona pellucida glycoprotein families indicates that oocyte sperm receptor activity is associated with different zone pellucida proteins in different mammalian species. AB - Porcine zona pellucida (pZP) glycoprotein 55 kDa is composed of two core polypeptides, denominated alpha and beta. Sperm receptor activity has been shown to be associated with the oligosaccharide structures attached to the pZP55 alpha component. Here, we report a simple one-step HPLC procedure for the isolation of the alpha- and beta-components of the 55 kDa pZP proteins after enzymatic partial deglycosylation. N-Terminal sequence and protein chemical analysis of native proteins and of internal peptides from the alpha and the beta forms has established their homology with the rabbit 55 kDa zona pellucida glycoprotein and mouse ZP3, respectively. This, in turn, is relevant for a standardization of the ZP nomenclature in mammalian species. Moreover, our results imply that the sperm receptor activity in diverse mammalian species reside on oligosaccharide chains attached to nonhomologous zona pellucida glycoproteins. We hypothesize that acquisition of species-specific activity on the oocyte zona pellucida may thus be related to a species-specific glycosylation process. PMID- 8216893 TI - Intrinsic stability and extrinsic stabilization of creatinase from Pseudomonas putida. AB - Creatinase (creatine amidinohydrolase, EC 3.5.3.3), a homodimer of 45 kDa subunit molecular mass, shows only limited functional stability, and is inaccessible to reconstitution after preceding deactivation, denaturation and dissociation. The enzyme has been characterized regarding its native and denatured states. Studying its unfolding characteristics in the presence of "extrinsic factors", such as DTE, BSA and glycerol, it was possible to define solvent conditions where the stability of the enzyme is significantly improved. Apart from protecting essential thiol groups and charge screening effects, the stabilization is caused mainly by preferential solvation. In the presence of 20% (w/v) glycerol, the kinetic analysis of the time course of denaturation indicates that a partially active folding intermediate, rather than the whole molecule, is involved in the stabilization. The mixed solvent improves the thermal stability, as well as the stability toward GdmCl and urea. PMID- 8216895 TI - Primary structure of subfragment-2 from adult chicken cardiac ventricular muscle myosin. AB - The complete primary structure of the subfragment-2 (S-2) from adult chicken cardiac ventricular muscle myosin has been determined by analysis of peptides derived from digests of S-2 with cyanogen bromide, lysyl endopeptidase, arginyl endopeptidase, and from hydrolysates of CNBr fragments with formic acid. This region composed of 520 amino-acid residues which span the connecting segment between subfragment-1 (S-1) and S-2 to the NH2-terminal portion of light meromyosin (LMM). Comparing this sequence with the partial sequence of the rod from the same chicken ventricular muscle myosin deduced from its nucleotides of cDNA which lacks 64 NH2-terminal amino-acid residues, 14 amino-acid differences and 3 deletion/insertions were recognized. Furthermore, the sequence of S-2 from adult chicken ventricular myosin was compared with corresponding sequences of rat alpha and beta cardiac myosin heavy chains (MHC) and human alpha and beta cardiac MHCs. The results show 83.7%, 82.1%, 83.1% and 82.1% sequence identities, respectively with almost similar degrees of similarities to both alpha- and beta MHCs. However, sequences of isoform-specific regions in this S-2 from adult chicken ventricular myosin showed clearly a higher homology to those of alpha MHCs than to beta-MHCs of mammalian cardiac myosins. PMID- 8216894 TI - Reconstitution of the core complex (alpha beta)3APCLC8.9 of the phycobilisome from Mastigocladus laminosus using the Lc8.9 linker polypeptide overexpressed in Escherichia coli. AB - The apcC gene from Mastigocladus laminosus encodes the linker polypeptide LC8.9 located in the phycobilisome core. A T7 RNA polymerase expression system was used to express the linker polypeptide LC8.9 from M. laminosus in Escherichia coli. The apcC gene product was expressed as an inclusion body which was solubilized in a buffer containing 8M urea. Final purification was achieved by ion exchange chromatography on Fractogel TSK CM 650 (S). In addition, a method for preparative isolation of the LC8.9 linker polypeptide from M. laminosus by reverse phase chromatography is presented. Both LC8.9 isolated from M. laminosus and overexpressed in E. coli were capable of reconstituting the complex (alpha beta)3APCLC8.9. The reconstituted complex was identical to preparations isolated from M. laminosus in terms of polypeptide composition, absorption and fluorescence emission spectroscopy. PMID- 8216896 TI - Human alpha 1-antichymotrypsin of pancreatic origin carries blood group determinants. AB - alpha 1-Antichymotrypsin was detected as a minor but normal component of pancreatic juice and found, with the aid of monoclonal antibodies and lectins, to differ from serum alpha 1-antichymotrypsin with respect to its carbohydrate moiety. alpha 1-Antichymotrypsin carries blood group determinants, as is typical for glycoproteins of pancreatic origin. PMID- 8216897 TI - Secondary fungal metabolites and their biological activities, III. Further metabolites from dual cultures of the antagonistic basidiomycetes Heterobasidion annosum and Gloeophyllum abietinum. AB - In addition to a preceding publication (Sonnenbichler, J., Bliestle, I.M., Peipp, H. & Holdenrieder, O. (1989) Biol. Chem. Hoppe-Seyler 370, 1295-1303), six further metabolites formed in dual cultures of the antagonistic fungi Heterobasidion annosum and Gloeophyllum abietinum are described; three of them represent unknown structures. The producing organisms have been identified. The metabolites fommanoxin from H. annosum and oosponol from G. abietinum show that the toxins can be detoxified by metabolization by the antagonistic fungus. The newly-described compounds have been tested for their fungicidal properties. PMID- 8216899 TI - Microbial metabolism of quinoline and related compounds. XIX. Degradation of 4 methylquinoline and quinoline by Pseudomonas putida K1. AB - A bacterial strain, designated K1, which utilizes 4-methylquinoline and quinoline as sole source of carbon, nitrogen and energy was isolated from soil. Based on its morphological and physiological characteristics, it was classified as Pseudomonas putida biovar B. Four metabolites of 4-methylquinoline degradation were isolated from the culture supernatant and identified as 4-methyl-2-oxo-1,2 dihydroquinoline, 8-hydroxy-4-methyl-2-oxo-1,2-dihydroquinoline, 7,8-dihydroxy-4 methyl-2-oxo-1,2-dihydroquinoline and 6-hydroxy-5-(2-carboxyethenyl)-4-methyl-1H 2-pyridone. Formation of the latter compound is suggested to proceed by decarbonylation of a putative meta-cleavage product of the 7,8-dihydroxy derivative. During growth on quinoline four compounds were released into the culture fluid, too. Upon isolation they were identified as 2-oxo-1,2 dihydroquinoline, 6-hydroxy-2-oxo-1,2-dihydroquinoline, 5-hydroxy-6-(3-carboxy-3 oxopropenyl)-1H-2-pyridone and 2H-pyran-2-on-[3,2b]-5H-6-pyridone. Thus it is proved, that Pseudomonas putida possesses two different catabolic pathways for various quinoline derivatives, which are induced selectively depending on the growth substrate. PMID- 8216898 TI - Lactational changes in the N-glycoloylneuraminic acid content of bovine milk gangliosides. AB - The N-glycoloylneuraminic acid (Neu5Gc) contents of milk and milk gangliosides from bovines were investigated during the different stages of lactation. The Neu5Gc content of milk is high in the colostrum (32% of the total sialic acid content of milk) and decreases thereafter until the end of the period considered (6% on day 30). When the Neu5Gc content of gangliosides was evaluated a similar profile to that of Neu5Gc in total sialic acids was found. Gangliosides from colostrum showed the highest Neu5Gc content (21-22% of the total sialic acid content of milk gangliosides). This content dropped towards the end of the period studied (8% on day 90). Our results indicate that a significant supply of Neu5Gc by the milk could be important for the newborn during the first days after parturition. PMID- 8216900 TI - Site-directed mutagenesis of the 2-haloalkanoic acid dehalogenase I gene from Pseudomonas sp. strain CBS3 and its effect on catalytic activity. AB - Two 2-haloalkanoic acid dehalogenases from Pseudomonas sp. strain CBS3 catalyse hydrolytic dehalogenation of chloroacetate and 2-chloropropionate. We used site directed mutagenesis to introduce specific changes in the dehalogenase I encoding gene (dehCI). Substitution of Asp-10 by Ala-10 resulted in complete loss of dehalogenating activity although expression of the 2-haloacid dehalogenase I was not affected in the mutant as shown by western blot analysis, and although comparison of the mutated enzyme with the wild type enzyme indicated that extensive rearrangements in the three-dimensional structure of the enzyme had not occurred. From these data we suggest that Asp-10 of 2-haloacid dehalogenases I from Pseudomonas sp. strain CBS3 may be the nucleophilic residue in the active site of this enzyme essential for halide release. PMID- 8216901 TI - Evidence for the degradation of type XI collagen by bovine intervertebral disc- and articular cartilage extracts. AB - Bovine intervertebral disc- and articular cartilage extracts contain a metalloproteinase system capable of degrading type XI collagen. The collagen degrading activity is rather low in unmodified extracts but increases considerably on metalloproteinase activation. The similarity between intervertebral disc and articular cartilage in their patterns of (casein degrading) metalloproteinases and type XI and type II collagen degradation is believed to suggest a similarity in the events underlying the degradative disorders of articular cartilage and intervertebral disc. PMID- 8216902 TI - Isolation and preliminary characterization of the cysteine-proteinases from the latex of Carica candamarcensis Hook. AB - The cysteine-proteinase chymopapain from Carica papaya L. is used for chemonucleolysis of damaged human intervertebral spinal discs. The purification of this enzyme is difficult. To overcome these problems, we were looking for a substitute among the cysteine-proteinases of Carica candamarcensis Hook. The latex from unripe fruits was collected in an aqueous solution of methylethanethiolsulfonate to prevent proteolytic activities. The soluble fraction of the lypophilized product provided four enzymatically active peaks (CC I-CC-IV) during chromatography on CM-Sephadex C-50 in sodium acetate buffer, pH5.0. They could be further purified by rechromatography under similar conditions. The isolated enzymes have been characterized by PAGE, analysis of the Fourier transform infrared spectra, preliminary studies of their specificities as well as a comparison of the N-terminal amino-acid sequences up to position 43. CC III proved to be glycosylated. CC-I and CC-III from Carica candamarcensis Hook are suggested to correspond to papain and chymopapain from Carica papaya L., respectively. PMID- 8216903 TI - Craniofacial surgery. PMID- 8216904 TI - Cortical resections for intractable epilepsy of extratemporal origin: experience with seventeen cases over eleven years. AB - Seventeen patients underwent surgery between 1981 and 1990 for intractable partial epilepsy arising outside the temporal lobe. Twelve had frontal seizure onset, two parietal, two occipital and one diffusely in the hemisphere. Localization was achieved using extraoperative electrocorticography (ECoG) in five cases and intraoperative ECoG was employed in 12. Fifteen patients underwent cortical resections, but two did not subsequently have a resection. Both of these had porencephalic cysts. Of the 15 who had resections six (40%) were seizure free after a mean of 7.3 years. One (7%) was almost seizure free, six (40%) had worthwhile improvement. Pathological examination revealed oligodendroglioma in three, recurrent meningioma in one, vascular malformations in two, glial hamartoma in one and gliosis in six. One case with gliosis initially was shown to have an underlying malignant astrocytoma 2 years later. All these patients had CT abnormalities prior to surgery. Two patients (13%) had no worthwhile improvement. Pathology in these two was ischaemic neurons and arachnoid thickening. Both had normal CT findings preoperatively. One patient had an increased hemiparesis postoperatively. There were three cases of postoperative infection. It is concluded that extratemporal resection can achieve good results for seizure control and intraoperative ECoG is an effective technique for localizing the epileptogenic area. The presence of a structural lesion carries a particularly favourable prognosis for seizure outcome and surgery should, therefore, be strongly considered in patients with intractable partial epilepsy who have evidence of underlying structural pathology. PMID- 8216905 TI - The pathophysiology of infant subdural haematomas. AB - The widely accepted theories concerning the pathophysiology of infant subdural haematoma (SDH) were formulated in the pre-computed tomographic (CT) scan era. Violent shaking is considered to be a crucial cause of SDH in non-accidentally injured infants. This theory has been re-examined in a clinical and CT scan review, and our findings have been correlated with results of recent head injury research. A retrospective review was conducted of all head injured infants (up to 18 months old) treated at Atkinson Morley's Hospital over a recent 20-year period (n = 100). Twenty-eight infants with a SDH were identified. CT scans were reviewed and each SDH greater than 0.5 cm thick was morphometrically analysed. Seventeen infants were Caucasian, 10 were non-Caucasian and one was of mixed race. A race-dependent pattern of SDH pathophysiology was noted, with non Caucasian infants with a head injury more likely to have a SDH than Caucasian infants (67 v 21%, p < 0.01). All had a history of, or radiographic and clinical findings most consistent with, an impact injury, and non-Caucasian infants were significantly more likely to have a normal scalp examination despite the impact injury (p < 0.05) and to have developed the SDH after a relatively trivial fall (p < 0.01). They were also more likely to have a large (> 0.5 cm thick) SDH (p < 0.05), and to suffer post-traumatic seizures (p < 0.05). Our findings do not support shaking as the only cause of infant SDH formation and also suggest that non-accidental injury is a less common cause of SDH than it is believed to be. PMID- 8216906 TI - Bacterial intracranial aneurysms. AB - This is a retrospective study of 25 patients with bacterial intracranial aneurysms treated in a single department over a 20-year period. The clinical presentation, investigation and treatment of these patients is discussed. The outcome of the treatment is assessed and is thought to be not as poor as previously reported. PMID- 8216907 TI - Nucleolar organizer regions in meningiomas. AB - Paraffin sections of 305 meningeal tumours were analysed for the presence of nucleolar organizer region (Ag-NOR) in the neoplastic cells, using a one step silver-colloidal staining method. The mean (+/- SEM) Ag-NOR counts were 2.73 +/- 0.21 for atypical and 2.91 +/- 0.18 for papillary variants of meningioma. In meningotheliomatous and transitional variants of meningioma, the mean Ag-NOR counts were 1.41 +/- 0.34 and 1.38 +/- 0.31, respectively. The recurrence rates were significantly higher in atypical meningiomas than in other histopathological variants (p < 0.05). Differences in the mean Ag-NOR numbers between meningothelial and transitional variants in their primary and recurrent tumours were not significantly different (p > 0.05). The results of this study indicates that estimation of Ag-NORs can be applied in predicting the aggressive clinical behaviour of primary meningeal tumours. PMID- 8216908 TI - Intracranial aspergillus granuloma. AB - Intracranial aspergillus granulomas over a 12-year period were studied retrospectively. Three distinctive types of presentations were seen, namely nine patients had the rhinocerebral form with primary involvement of the air sinuses and secondary involvement of the skull base, cranial nerves and brain, three patients with the apparently purely intracranial form presented like any other space occupying lesion and one patient who had a 'stroke-like' presentation had a parasellar lesion. None of these patients were immunocompromised. The clinical features, and the medical and surgical options are discussed together with outcome. PMID- 8216909 TI - Midline aneurysms of the vertebrobasilar junction: an effective anterior approach. AB - There are acknowledged difficulties associated with operations on midline aneurysms at the vertebrobasilar junction. This report describes a series of such aneurysms treated by an anterior approach using a Le Fort maxillotomy to gain access via the clivus to the aneurysm. In each case the aneurysm was dealt with satisfactorily with no long-term morbidity or mortality. Attention is directed to the necessity for a water-tight dural seal postoperatively. We advocate wider use of this technique in appropriate circumstances. PMID- 8216910 TI - Whither preoperative shunts for posterior fossa tumours? AB - Some degree of hydrocephalus is present in almost all cases of medium to large posterior fossa tumours. The initial symptoms in such cases are usually due to the hydrocephalus and the consequent increased supratentorial pressure, and more often precede the symptoms primarily due to the local invasion and compression of the brain stem and cerebellum by a significant length of time. In our experience, based on 62 posterior fossa tumour operations, insertion of a cerebrospinal fluid (CSF) diverting shunt because of hydrocephalus makes the subsequent tumour excision more difficult and hazardous. The various problems presumed to be related to preoperative shunt surgery are discussed in this report. It is concluded that preoperative shunts for posterior fossa tumours are rarely indicated. PMID- 8216912 TI - Hemifacial spasm: early postoperative normalization of blink reflex latency. AB - Electrophysiological improvement in the blink reflex latency after neurovascular decompression of the facial nerve in patients with hemifacial spasm is believed to be related to remyelination and occurs 2-8 months after surgery. We report a patient with hemifacial spasms for 3 years, in whom the increased blink reflex latency returned to normal within a week after surgery. This suggests that compression without demyelination may be responsible for increased blink reflex latency in some of the patients with hemifacial spasms. PMID- 8216911 TI - In vitro study of the effect of photodynamic therapy on pituitary adenomas. AB - Photodynamic therapy (PDT) has been employed in the management of recurrent cerebral gliomas, but its activity against pituitary adenomas has not been specifically studied. An in vitro study of the effects of PDT against a variety of pituitary adenomas was conducted. It was found that PDT using haematoporphyrin derivative as a photosensitizer showed dose dependent activity against a variety of pituitary adenomas. The activity of PDT against pituitary adenomas should be investigated further and may hopefully provide a useful form of adjuvant therapy for preventing recurrence of micro-invasive pituitary adenomas or dealing with established recurrence after surgery and radiotherapy. PMID- 8216913 TI - Selective decompression and translaminar articular facet screw fixation for lumbar canal stenosis and disc protrusion. AB - A technique is described for lumbar canal stenosis and disc protrusion combining safe and selective decompression and translaminar screw fixation. After experience with 166 cases from 1987 to 1991 we consider this technique particularly suitable for the treatment of lumbar spinal stenosis and also for the few cases of lumbar disc displacement which need a primary fusion. PMID- 8216914 TI - Pyomyelia: an intramedullary spinal abscess complicating lumbar lipoma with spina bifida. AB - We report a case of spinal dysraphism, complicated by an intramedullary spinal abscess (IMSA). The magnetic resonance images of this case are shown and the pathophysiology of this condition is discussed. PMID- 8216915 TI - Malignant osteoblastoma of the skull. AB - A bone tumour of intermediate grade malignancy in the skull is described. These tumours are extremely rare and share several histological features with the benign osteoblastomas and low grade osteosarcomas. They may be associated with local invasion and pulmonary metastases. Treatment of this tumour in the skull poses several problems in view of its proximity to the cerebral cortex. PMID- 8216916 TI - Schwannoma of the medulla oblongata. PMID- 8216917 TI - Dural arteriovenous malformations of the ethmoidal region: report of two cases. AB - Dural arteriovenous malformations of the ethmoidal region are extremely rare. They are usually supplied by the ipsilateral anterior ethmoidal artery with contralateral contribution in about half of the cases. They are characterized by a fistulous nidus within the dura, and their progression seems to involve a retrograde leptomeningeal vascular stasis with formation of varices and venous aneurysms. They have more propensity to rupture than dural malformations in other locations. Two patients who presented with an acute frontal hemorrhage are reported. PMID- 8216918 TI - Cervical intraspinal lipoma in a pregnant patient. AB - Tetraparesis developing in a female, during pregnancy, was found to be due to an intradural cervical lipoma, associated with a subcutaneous lipoma at the same level in the midline posteriorly. Sub-total removal produced a return to near normal function with the patient being fully ambulant 7 months later. PMID- 8216919 TI - Pituitary apoplexy presenting as multiple ocular nerve palsies of sudden onset. AB - An acromegalic patient with pituitary apoplexy presented with multiple ocular nerve palsies with full visual fields. High resolution CT confirmed a pituitary tumour. We believe this clinical combination to be unique. PMID- 8216920 TI - Pathogenesis of post-traumatic syringomyelia. PMID- 8216921 TI - Virus infections in mice with targeted gene disruptions. AB - The experimental dissection of the ways that the various cells and molecules of the immune system interact to promote virus clearance has been greatly facilitated by the availability of mice with targeted disruptions of key genes. New insights are emerging, and details of host resistance mechanisms that could only be inferred for the in vivo situation are now being clearly established. PMID- 8216922 TI - CD8+ cytotoxic T cell therapy of cytomegalovirus and HIV infection. AB - The development of CD8+ cytotoxic T cell responses to viral pathogens is crucial for the prompt resolution of acute infections and for the control of viruses which persist in the host. Thus, cytomegalovirus often causes life threatening disease in immunosuppressed humans who fail to develop or maintain CD8+ cytotoxic T cells. Similarly, the loss of CD8+ cytotoxic T cell responses to HIV correlates with the development of AIDS. Recent investigations in the immunobiology of cytomegalovirus and HIV have resulted in the application of immunotherapeutic strategies designed to reconstitute or augment deficient CD8+ cytotoxic T cell responses to these human pathogens. PMID- 8216923 TI - Cellular immunity to intracellular bacteria. AB - Great progress has been made in understanding the mechanisms bacteria use to invade, survive and move within eukaryotic cells. It is clear that bacteria have found ways to manipulate host cell signal transduction pathways and the cytoskeleton to their advantage. To defend against prokaryotic invaders, the immune system has evolved mechanisms for the specific recognition of bacterial antigens. PMID- 8216924 TI - Immunity to mycobacteria. AB - Recent progress in the field of immunity to mycobacteria has centered on T cell subset responses and the cytokines these cells secrete. In addition, there has been steady progress in identifying and characterizing several classes of major mycobacterial proteins; included amongst these are the secreted/export proteins of Mycobacterium tuberculosis, which several laboratories now believe may represent the key protective immunity-inducing antigens of the bacillus. PMID- 8216925 TI - The role of natural killer cells in innate resistance to infection. AB - Natural killer cells were first identified by their cytotoxic activity against tumor cells, suggesting a role in immunological surveillance against neoplasia. However, there is now increasing evidence that natural killer cells are important mediators of innate resistance against a variety of pathogenic micro-organisms. Recently, several important advances have been made in our understanding of how these cells are activated during infection, the contribution of cytokines derived from natural killer cells to host resistance and their influence on the development of antigen-specific T-cell responses. PMID- 8216926 TI - Type 2 cytokines and negative immune regulation in human infections. AB - Recent studies indicate that the human immune response to infection is regulated by the balance between the T helper type 1 cytokines, interleukin-2 and interferon-gamma, and the T helper type 2 cytokines, interleukin-4, interleukin-5 and interleukin-10. Interleukin-4 and interleukin-10 can facilitate antibody production but can also suppress cell-mediated immune responses. The net effect of these negative immunoregulatory cytokines is to favor progression of infection. PMID- 8216927 TI - Effector functions of activated macrophages against parasites. AB - Evidence in experimental animals indicates a major role for cytokine-activated macrophages as effector cells in protective immunity against parasites. Research on cytokine function during this past year has contributed many insights into the immune mechanisms regulating murine macrophage function as well as the effector molecules employed by these cells to kill both intracellular and extracellular parasites. PMID- 8216928 TI - T-cell and cytokine responses in leishmaniasis. AB - Intracellular pathogens, particularly those that inhabit lymphocytes and macrophages, represent unique challenges to the immune system. Leishmania are protozoan parasites that replicate exclusively in macrophages and are thus in an excellent position to influence lymphocyte responses. T cell responses are critical in determining the outcome of infections with Leishmania. In both murine and human infections, strong T helper type 2 responses have been associated with disease, and a decreased or absent T helper type 2 response has been associated with healing. PMID- 8216929 TI - Immunity to Toxoplasma gondii. AB - Recent advances in our understanding of the immunological mechanisms involved during infection with Toxoplasma gondii include evidence for the role of different subsets of lymphocytes and cytokines in acute infection as well as in reactivation of chronic infection. The mechanisms of presentation of T. gondii antigen have been clarified recently, and animal models of toxoplasmosis that mimic disease observed in AIDS patients developed. PMID- 8216930 TI - Immunity and immunoregulation in helminth infections. AB - Parasitic helminths continue to be a major cause of morbidity in human populations, particularly in the tropics and subtropics. The need for effective vaccines that minimize worm burdens, thus reducing associated pathology, is evident. With this goal in mind, an intense research effort is in progress to characterize immune responses to helminths, especially in the context of recent developments in our understanding of the cytokine network. The growing realization that the parasites can themselves subvert host immune responses to their own advantage makes the task of vaccine development that much harder. PMID- 8216931 TI - Immunity to blood stages of malaria. AB - Those developmental stages of malaria parasites that infect erythrocytes are responsible for the severe morbidity and mortality associated with this disease. The nature and specificity of the slowly acquired immunity seen in endemic populations remain to be defined, but significant progress has been made recently in identifying specific blood-stage proteins, characterizing immune responses to them, and exploring the dynamics of non-specific host responses to infection. PMID- 8216932 TI - Transmission-blocking immunity against malaria and other vector-borne diseases. AB - Antibodies to sexual stage malaria parasites block transmission of Plasmodium by female mosquitoes. With the recent isolation of genes encoding several of the target antigens of transmission-blocking antibodies, the development of a subunit transmission-blocking vaccine against malaria is now a realistic goal. PMID- 8216933 TI - Primary T-cell immunodeficiencies. AB - The phenotypes of many primary T-cell immunodeficiencies have been described, including diseases associated with defective T-cell differentiation and/or activation. Recently, genotypes have been defined for some of them, such as X linked severe combined immunodeficiency and CD3 deficiencies (or hyper IgM syndrome). Phenotype/genotype correlation studies open a fruitful way to a better understanding of primary T-cell immunodeficiencies. PMID- 8216934 TI - Immunodeficiency-inducing retroviruses. AB - The plethora of disease syndromes (dystrophy of various organ systems, malignancies and opportunistic infections) caused by HIV are all potentiated by the profound virus-induced immunosuppression that accompanies this infection. The mechanism of this severe immunosuppression is poorly understood and the subject is currently being pursued in studies of HIV-infected patients and in animals infected with other immunodeficiency-inducing retroviruses. PMID- 8216935 TI - Immunotherapeutic strategies in the treatment of HIV infection and AIDS. AB - The immune response against HIV does not result in complete viral clearance. Recent interventions have focused on novel strategies to modify human anti-HIV immunity. Active vaccination of patients with HIV infection (vaccine therapy) safely alters the immune repertoire against HIV. This unique approach will provide insight into the immunoregulatory consequences of HIV-specific innate and adaptive immune responses, and hopefully define the immunological Achilles heel of HIV. Once defined, researchers, aided by current biotechnological techniques, can rationally design future vaccines and immune based therapeutic products. PMID- 8216936 TI - Immunity to infection. PMID- 8216937 TI - Immunodeficiency. PMID- 8216938 TI - Sizing of large DNA molecules by hook formation in a loose matrix. AB - We present details on how to implement a newly developed methodology, Optical Contour Maximization (OCM), for accurately sizing large DNA molecules. Agarose gel containing stained DNA is cast between a slide and a coverslip, and molecules moved by an applied electrical field are observed using fluorescence microscopy. The molecules of interest lie in the interface formed between the coverslip and gel. DNA movement in this region is largely confined to lateral motions. When a DNA molecule snags an obstacle, it elongates, forming a metastable hook that can persist for several seconds. We found that the longest observed hook contour length can be determined from rapidly collected images. This maximized length shows a linear correlation with reported size [X.H. Guo, E.J. Huff & D.C. Schwartz, Nature 359, 783 (1992)] Successful measurements require a critical balance between the voltage needed for full elongation, and the unwanted effects of too large a voltage: fewer metastable hooks form, they dissipate faster, molecule breakage becomes a problem, and faster image collection becomes necessary. We measured apparent contour length as a function of applied voltage and determined an optimal voltage for our apparatus, using a singly anchored 114kb molecule. The measurement precision is estimated from the distribution of results. We expect that OCM will find utility in physical mapping and molecular karyotyping of lower eucaryotes of medical importance. PMID- 8216939 TI - Crystal packing effects on A-DNA helix parameters: a comparative study of the isoforms of the tetragonal & hexagonal family of octamers with differing base sequences. AB - The helix and base pair parameters of A-DNA octamers have been compared having different base sequences both in the tetragonal and hexagonal crystal systems. For the eight structures in the tetragonal family, the twist, rise, slide, inclination and tilt are essentially the same, influenced by the similarity in crystal packing. The propeller twist and the base pair buckle display small sequence dependent variations. But the base pair roll appears to be changed by the specific intermolecular hydrogen bonding interactions. For four of the five octamer structures in the hexagonal family, the base pair rise, slide, inclination, tilt, as well as the propeller twist and buckle are all very similar, while the twist angle and the base pair roll are not. The intermolecular hydrogen bonding interactions seem to be primarily responsible for the differences in the roll angle in the tetragonal structures but for both the roll and twist angles in the hexagonal structures. These results demonstrate that the majority of the observed helix base pair parameters for A-DNA octamers in crystals are affected by the crystal packing environment, while a few parameters, like propeller twist and base pair buckle display some base sequence dependence. PMID- 8216940 TI - Overall and internal protein dynamics in solution studied by the nonselective proton relaxation. AB - A new algorithm for the analysis of nonselective proton relaxation data in protein solution is presented. T1 and T2 of protein protons in lysozyme and RNase solutions were measured at three resonance frequencies--11, 27 and 90 MHz. In addition we measured water T1 dispersions in lysozyme solutions over the frequency range of 10 kHz--10 MHz on a field-cycling installation. It was found that the correlation function of protein Brownian tumbling as a whole is nonexponential: in addition to a component with the usual correlation time tau t it contained also a component with a correlation time exceeding tau t by approximately an order of magnitude and with a small relative amplitude. The experiment shows that the parameters of the slow component of the tumbling correlation function depend both on the concentration and on the pH of the protein solution. To explain the results obtained one must take into account the interprotein electrostatic interactions in solution. All protein molecules in solution experience electrostatic torques from their neighbors and this gives rise to an anisotropy in the protein Brownian tumbling. The lifetime of this anisotropy is controlled by the translational diffusion of proteins. PMID- 8216941 TI - Investigation of conformational equilibrium of polypeptides by internal coordinate stochastic dynamics. Met5-enkephalin. AB - The equilibrium population of different conformational states of a polypeptide can in principle be obtained by a very long molecular dynamics simulation. The method of internal coordinate molecular dynamics earlier developed in this laboratory (A.K. Mazur and R.A. Abagyan J. Biomol. Struct. Dyn. 6,833 (1989)) allows one to use time steps much larger than usual for computing molecular trajectories. It is shown here that the sampling of the conformational space can be additionally enhanced by adding a random component to the set of forces applied to atoms. We describe the algorithms by which the random force is introduced and also a special method which excludes the fast rotation of polar hydrogens from equations of motion but keeps them movable. As a result the task stated in the title becomes realistic. Internal coordinate stochastic dynamics is applied for scanning the conformational space of the pentapeptide Met5-enkephalin which is a common test example widely used in theoretical studies. A large number of conformational transitions is observed during the 20 ns simulation starting from the global energy minimum thus allowing us to arrive at a nearly Boltzmann distribution of populations of conformational states. A few states are found which are distinguished by high apparent configurational entropy which turn out to correspond well to experimentally observed conformations of enkephalins. PMID- 8216942 TI - The aggregation properties of some bradykinin analogs. AB - Bradykinin (BK) is a peptide hormone with sequence Arg1-Pro2-Pro3-Gly4-Phe5-Ser6 Pro7-Phe8-Arg9 and has been implicated in a multitude of pathophysiological processes such as the ability to lower systemic blood pressure and stimulate pain. Bulky, beta-branched D-aliphatic residues at position 7 combined with bulky L-aliphatic residues at position 8 have now been observed to yield strong antagonists. Nuclear magnetic resonance studies have been carried out on many of these molecules with a view to determining their solution conformations. However, two such analogs, namely DArg-[Hyp3, Thi5, DSer6, DCpg7, Cpg8]-BK [I] and DArg [Hyp3, DSer6, DCpg7, Cpg8]-BK [II] (Cpg = alpha-cyclopentyl-glycine; Hyp = 4 hydroxy-L-proline, Thi = beta-(2-thienyl)-L-alanine), have exhibited an abnormal, non-linear temperature dependence for the amide NH proton of Cpg8. The NH of Arg9 also shows a slightly non-linear temperature dependence at higher temperatures above 25 degrees C. In addition, a very slow exchange rate for the NH protons of DCpg7, Cpg8 and Arg9 indicated aggregation of these two analogs, which was confirmed using the circular dichroism experiments. PMID- 8216943 TI - An aggregating elastin-like pentapeptide. AB - Synthetic VGGVG, a "monomeric" unit of the glycine-rich regions of elastin, has been investigated for its molecular and supramolecular properties. In aqueous solution the pentapeptide showed conformational features strongly concentration dependent. CD and NMR studies suggested a partial unfolding on increasing the concentration. Electron microscopy, on the other hand, evidenced extensive aggregation of the pentapeptide yielding elastin-like supramolecular structures constituted either by twisted ropes or by banded fibrils. PMID- 8216944 TI - Raman and infrared studies of wet-spun films of Na-hyaluronate. AB - Raman and infrared (IR) studies of Na-hyaluronate films have been performed as a function of relative humidity (RH) and temperature. These data show a number of vibrational modes. Certain of these modes are evident in both the Raman and IR data. Changes in the Raman spectra are observed at the order-disorder phase transition (between 84 and 90% RH) and suggest that the molecular conformation changes at the phase transition. PMID- 8216945 TI - Empirical force field analysis of the revised structure of coenzyme F430. Epimerization and geometry of the corphinoid tetrapyrrole. AB - We undertook an empirical force field analysis of the conformational changes that accompany the diepimerization of coenzyme F430. The crystal structure of 12,13 diepi F430M was used as a test of the parameter set and as the basis for the calculations. The individual pyrrole rings in 13-epi and 12,13-diepi F430 adopt alternating half chair conformations leading to a ruffled macrocycle, native F430 is also ruffled but the individual pyrroles are planar. The 12,13 di-dehydro F430 and native F430 conformations are extremely similar, this accounts for the experimental observation that reduction of 12,13 di-dehydro-F430 forms native F430 and not 12,13-diepi F430. Native F430 can easily accommodate both square planar and, by bending, trigonal bipyramidal coordination geometries about nickel. We suggest that bent trigonal bipyramidal form is the conformer bound to the protein and that direct binding of the amino acid side chains to nickel is probably not important. PMID- 8216946 TI - Relationships among rise, cup, roll and stagger in DNA suggested by empirical potential studies of base stacking. AB - Empirical analyses of experimental data have recently revealed a strong correlation in B- and A-DNA crystal structures between rise of the base pair steps and their cup, or the difference between roll and cup. We show here using empirical potentials that a major part of this correlation can be explained by the base stacking forces. Our calculations further demonstrate that the correlation depends on the base sequence while the dependence is strongest with the C-G step. We also show that small values (which lie beyond resolution of the X-ray diffraction data obtained with the DNA fragment single crystals) of base pair stagger can completely substitute for the effects of roll in the correlation. The present and our previous studies demonstrate that the base pair buckle and stagger can substantially affect base stacking in DNA so that variability of these parameters cannot be neglected in the theoretical analysis of the base sequence effects on DNA conformation. PMID- 8216947 TI - Molecular dynamics study of the base pair opening process in the self complementary octanucleotide d(CTGATCAG). AB - We report an analysis of a 200 ps Molecular Dynamics simulation of the double stranded oligonucleotide d(CTGATCAG) in the presence of 1534 water molecules and 14 Na+ ions. We focus on the opening process of Thymine 5, by analyzing in detail the glycosidic bond rotational motion about the helix axis. The present analysis is mainly based on autocorrelation functions and on mean square displacements. We show that the opening of the base has a Brownian character and we find a rotational diffusion coefficient of 4.7 rad2s-1. Furthermore we estimate the DNA torsional constant to be about 0.5 10(-18) J.rad-2 and the RMS of the angular displacement to be 8.3 degrees. All these values are in fair agreement with those determined experimentally by fluorescence polarization of DNA-Ethidium bromide complexes. This shows that the rotational motions of the bases detected in the range 10(-9)-10(-7) s. by fluorescence techniques are the same as those analyzed in the present study (10(-12)-2 10(-10) s). PMID- 8216948 TI - Characteristics of the large (dA).(dT) homopolymer tracts in D. discoideum gene flanking and intron sequences. AB - D. discoideum, the slime mold, is one of the most AT rich eukaryotic genomes known. In this paper we examine this organism's database for overlapping N-tuples of high frequency and find A and T tracts possess among the highest frequencies in flanking sequences but not in coding sequences. We examined both overlapping and non-overlapping frequencies of the A, T, G and C homopolymer tracts of 2 < N < 6. Overlapping (dG).(dC) and (dA).(dT) tracts occur at greater frequencies than expected, based on random occurrence. Long (dA).(dT) tracts of N > 10 occur at well above expected frequencies in flanking and intron regions, while (dG).(dC) tracts above N = 5 are rarely found. Some of the implications of these findings for tract origins in slip-strand replication and for chromatin structure are discussed. PMID- 8216949 TI - Spectroscopic studies on the binding of methylene blue to poly(riboadenylic acid). AB - The binding of methylene blue (MB) to poly(rA) was studied using UV and CD spectroscopy at neutral and acidic pH, in which poly(rA) exists as a single strand and a duplex respectively. UV spectroscopic studies and analysis of equilibrium binding data show that salt increases the cooperativity parameter but reduces the binding between the cationic dye and the negatively charged phosphate groups. The binding constant for the single strand-MB complex decreased from 1.15 x 10(5) M-1 to 7.62 x 10(3) M-1 while the cooperativity parameter increased from 9 to 71, when salt concentration was increased from 1 mM to 200 mM. At neutral pH, changes in the induced circular dichroism of MB-poly(rA) complex with ionic strength show predominance of electrostatic binding to the phosphate group externally on the poly(rA) chain; a partial intercalation between the adenine bases is also indicated. A red shift in the visible absorption band and the ICD profile of the double stranded poly (rA)-MB complex suggest an electronically coupled intercalation mode for the dye binding at pH 4.2. PMID- 8216950 TI - The effects of cobalt-hexammine and cobalt-pentammine cations on the solution structure of calf-thymus DNA. DNA condensation and structural features studied by FTIR difference spectroscopy. AB - The interaction of calf-thymus DNA with cobalt-hexammine and cobalt-pentammine cations was investigated, in aqueous solution at pH 6-7 with cation/DNA(phosphate) molar ratios r = 1/80, 1/40, 1/20, 1/10, 1/4, 1/2 and 1, using Fourier Transform infrared (FTIR) difference spectroscopy. Correlations between spectral changes, DNA condensation and helical stabilization due to the cation interaction as well as conformational features are established. At a very low cation concentration (r = 1/80), the binding of cobalt-hexammine cation with DNA is through the H-bond formation between cation NH3 groups and the PO2 groups of the backbone, resulting in duplex stability. As the cation concentration increases, hydrogen bonding expands towards guanine N-7 and O-6 atoms. At r > 1/20, DNA condensation occurs with major reduction in the intensity of several DNA in-plane vibrations and that of the phosphate group. The cobalt-pentammine cation binding is via the PO2 groups (directly) at very low metal cation concentration (r = 1/80) and the guanine N-7 and the O-6 groups (indirectly) at higher ratios. At r > 1/10, DNA condensation begins with some degree of direct cation-base binding. No major conformational changes from the B-family structure were observed before and after DNA collapse, in the presence of cobalt-ammine cations. PMID- 8216951 TI - Effect of organic effectors on chromatin solubility, DNA-histone H1 interactions, DNA and histone H1 structures. AB - We have extended our previous investigations on the effect of organic osmolytes (glycine, proline, taurine, mannitol, sorbitol and trimethylammonium oxide (TMAO)) on chromatin solubility, to the study of their influence on DNA stability and DNA-histone interactions. Our aim was to understand the molecular origin of the protection effects observed. To this end, we determined the amount of histone H1 required to precipitate DNA or H1-depleted chromatin, at various salt concentrations, in the presence of the above mentioned organic compounds. We found a shift of the H1/DNA ratio required to reach 50% precipitation, towards higher values. Taurine was the most efficient compound followed by mannitol and glycine, then sorbitol and proline. On the contrary, TMAO favoured the precipitation process. We attempted to interpret these results on the basis of Manning's counterion condensation theory. Changes in histone H1 structure folding and in DNA melting temperature Tm were also analyzed. Glycine, taurine, sorbitol and TMAO increased the degree of secondary structure folding of the protein while mannitol and sorbitol had no effect. Taurine, glycine and proline decreased the Tm of DNA, TMAO largely destabilized DNA, but mannitol and sorbitol had no effect. Measurements of NaCl activity in the presence of organic osmolytes did not reveal sufficiently large changes to account for their protection effect against chromatin precipitation. The osmotic coefficient j of the organic effectors solutions increased in the order: taurine < glycine < sorbitol < mannitol < proline << TMAO. For the two latter compounds, the j values increased above 1 at high concentration. We consider that the organic compounds investigated may be classified into three categories: (i) class I (zwitterionic compounds: glycine, proline, taurine) would produce sodium ions release from the DNA surface; (ii) class II (the very polar molecule TMAO) would increase sodium counterions condensation on DNA together with histone H1 folding; (iii) class III compounds (mannitol and sorbitol) would possibly produce a modification of NaCl activity but no definite explanation could be found for the complex behavior of these compounds. PMID- 8216952 TI - Convoys of social support: an intergenerational analysis. AB - Within the Convoy Model, social networks are viewed as dynamic hierarchic structures surrounding the individual throughout life. As a step toward empirical definition of convoy structure and function across the life span, a bicultural sample (N = 159) of young adult women, their mothers, and their grandmothers were queried. Comparable results were obtained across generations and cultures with regard to network size, the amount of support provided by the network, and the nomination of close family members as primary sources of support. However, there was a marked shift across generations in the balance of familial versus friendship relations. Younger persons included fewer family members and more friends in their networks, and they received more support from friends. These cross-sectional results are consistent with the Convoy Model and suggest that longitudinal research is warranted. PMID- 8216953 TI - Physical and mental health in later life: the self-system as mediator. AB - The purpose of this research was to investigate how the self-system mediates the relationship between physical health and mental health in elderly women. Three theoretical perspectives were examined: social integration (self in relationship to the social structure), social comparisons (self in relationship to others), and self-discrepancies (internal self-evaluations). Community-dwelling elderly women (N = 243) completed self-report instruments measuring the various self assessments, physical health, and 3 mental health outcomes: psychological distress, well-being, and developmental outcomes. Social integration and social comparisons mediated the effects of physical health on all 3 outcomes. PMID- 8216954 TI - References in conversation between young and old normal adults. AB - This study compared the way in which young and elderly adults cooperate to achieve a mutually acceptable reference. Pairs of young and elderly interlocutors performed a repeated referential communication task in which they were asked to converse about arranging complex figures in a particular order. With repetition of the task, both partners, regardless of age, needed fewer words and speaking turns to find mutually acceptable references. However, the older Ss were slower to benefit from the repetition and required more collaborative work to reach an agreement. The elderly were less likely to take previously shared information into account; they produced proportionally less requests for potential elaboration, and they were more likely to be idiosyncratic in their interpretation of the referents. PMID- 8216955 TI - Distinction between quality and quantity of problem-solving responses among depressed older women. AB - The purpose of this project was to investigate the extent to which depressed and nondepressed community-dwelling older women differed in their problem-solving responses to vignettes describing problematic situations common in this population. Contrary to expectations, the depressed and nondepressed older women showed an equal capacity to follow traditional problem-solving steps. There were differences, however, in the quality of solutions generated for dealing with social isolation and interpersonal conflict as judged by peer evaluators. Further work is needed in understanding the components of effective problem solving most important for adjustment to real-life difficulties. PMID- 8216956 TI - Handwriting performance in younger and older adults: age, familiarity, and practice effects. AB - The main goals of 2 experiments on the aging of handwriting skills were to investigate (a) age differences in speed of handwriting performance, (b) effects of task familiarity on age differences in performance, and (c) effects of practice on age differences in performance. Younger adults performed reliably faster than older adults on all tasks. An Age X Familiarity interaction in both experiments indicated that age differences were magnified for unfamiliar but attenuated for familiar tasks. In the second experiment, an Age X Trial interaction revealed that older adults improved at a faster rate than younger adults. Regressions with initial trial data indicated that the older were slower than the younger adults by a factor of about 1.6. With practice, however, this slowing factor was only 1.02. The results suggest that familiarity and practice play a role in speed of handwriting. PMID- 8216957 TI - Evidence for the selective preservation of spatial selective attention in old age. AB - Younger and older adults were tested in 2 versions of the Stroop color-word task: a color-block version in which the color word was adjacent to a color block and a color-word version in which the word was printed in color. An advance cue preceded the stimulus by 100 to 300 ms, indicating where it would appear. Age differences were small on the color-block version and large on the color-word version. These results are consistent with the speculation that posterior brain attention systems responsible for selecting a spatial location are relatively well preserved with advancing age but that anterior brain attention systems responsible for selecting a line of processing are compromised. PMID- 8216958 TI - Memory aging as a general phenomenon: episodic recall of older adults is a function of episodic recall of young adults. AB - The focus of this study was on the relationship between young and older adults' performance on tasks of deliberate recall from episodic memory. A meta-analysis on 91 relevant studies (comprising a total of 154 conditions) was conducted. It was found that 83% of the variance in older adults' recall probability was accounted for by a quadratic function using young adults' recall probabilities as predictors. No significant interaction with age of older adults was found. Interaction with task type was, however, significant, resulting in separate functions for list recall, prose recall, and paired-associate recall. The results point at the importance of the main effect of age in studies on memory aging. PMID- 8216959 TI - The effects of age, illustrations, and task variables on the performance of procedural assembly tasks. AB - Older adults may be disadvantaged in the performance of procedural assembly tasks because of age-related declines in working memory operations. It was hypothesized that adding illustrations to instructional text may lessen age-related performance differences by minimizing processing demands on working memory in the elderly. In the present study, younger and older adults constructed a series of 3 dimensional objects from 3 types of instructions (text only, illustration only, or text and illustrations). Results indicated that instructions consisting of text and illustrations reduced errors in construction for both age groups compared with the other formats. Younger adults, however, outperformed older adults under all instructional format conditions. Measures of spatial and verbal working memory and text comprehension ability accounted for substantial age related variance across the different format conditions but did not fully account for the age differences observed. PMID- 8216960 TI - Aging and memory for frequency of occurrence of novel, visual stimuli: direct and indirect measures. AB - Memory for frequency of occurrence typically is investigated using familiar stimuli (e.g., words) and with "direct" tests of memory; that is, the subject is required to state explicitly how often an item occurred or which item occurred more often. Experiments 1 and 2 examined the effects of age on the ability to make judgments (i.e., direct tests) regarding the frequency of occurrence of words and of novel, visual stimuli (Japanese ideograms). In Experiment 3, young and old subjects were compared on "indirect" measures of memory for frequency of occurrence of these ideograms, as indexed by the mere exposure effect. On the direct test of memory, elderly and young subjects did not differ when shown words, but elderly were impaired compared with young subjects when ideograms were presented. When tested indirectly, both groups were sensitive to the frequency of occurrence of ideograms. The pattern of results replicates and extends previous findings regarding performance dissociations between direct and indirect measures of memory in aging. PMID- 8216961 TI - Dimensionality and clustering in the semantic network of patients with Alzheimer's disease. AB - The organization of semantic memory in patients with Alzheimer's disease (AD) was investigated with a triadic comparison task. A multidimensional scaling statistic was used to analyze proximity data and to generate 3-dimensional cognitive maps that were then compared by a discriminant function analysis. The results suggest that the structure of semantic memory in AD patients differs from that of elderly normal controls (NC) in 2 ways. First, AD patients are less consistent in using the attributes (predation, domesticity, and size) of concepts. Second, AD patients focus primarily on concrete perceptual information (size), whereas NC Ss stress abstract conceptual knowledge (domesticity). These results are consistent with the notion that AD is characterized by a breakdown in the structure of semantic knowledge. PMID- 8216962 TI - Aging and forgetting in prospective and retrospective memory tasks. AB - Ss aged 52-83 years were asked to name 30 famous people 4 times over the course of an hour and to respond to 2 targets (a beard and a pipe) by marking the trial number on the response sheet. Initial performance in the prospective memory task was related only to a measure of incidental learning. Subsequent forgetting (i.e., success followed by failure) occurred more often for older Ss than for younger Ss, but there was no difference between the age groups in recovery (i.e., failure followed by success). Forgetting was predicted by age, even after a composite measure of general ability was included in the regression. Recovery was related to general ability alone. These results both replicate and extend those from a reanalysis of a previous study (Maylor, 1990a). They provide a striking contrast with the effect of age on retrospective memory, namely, age-related impairment on initial performance but no effect of age on subsequent forgetting. PMID- 8216963 TI - Manual performance of a repeated pattern by older and younger adults with supplementary auditory cues. AB - Ss performed the same M-shaped manual movement pattern on repeated trials using a visual display of instantaneous error. With practice, Ss' effective time delays were diminished by increased anticipation as evidenced by an increased correlation of their movement patterns with the input velocity. However, younger adults had lower error scores, performed larger movements, and had shorter effective time delays than did older adults. Supplementary auditory displays additionally contributed to greater anticipation. However, men exhibited this effect most with an auditory display of input velocity and women with an auditory display of input position. This benefit of the auditory displays did not carry over after these displays were withdrawn. When the visual display was additionally withdrawn, benefits of the auditory training were manifest among the older adults as relatively greater temporal modulation of movement. PMID- 8216964 TI - Future time perspective, response rates, and older persons: another chapter in the story. AB - Data quality is compromised when response rates to items vary with age group. Shmotkin (1992) found a 29% nonresponse rate to future-oriented items in persons older than 60 years and suggested future apprehension as a cause. The authors administered similar items to 251 older persons and found fewer instances of nonresponding to future-oriented items. On the basis of the high response rate to an enlarged Cantril ladder measuring future quality of life, presented in interview, the authors question the generality of future apprehension as a determinant of nonresponding. The authors suggest that mode of administration, size of items, and scale complexity, as well as future apprehension, are determinants of nonresponding to future-oriented items and scales. PMID- 8216965 TI - Age differences in word finding in discourse and nondiscourse situations. AB - Measures of word finding in discourse (video description task) and nondiscourse situations (word fluency tasks) were obtained from a sample of 90 community dwelling healthy adults. Age differences were found in the accuracy and uncertainty of the labels used to refer to the characters and objects depicted in the video description task and in the number of correct responses in the category fluency task. There was a significant amount of shared variance between the 2 types of tasks. More important, there was a significant amount of variance in the video discourse task associated with age that was independent of performance in the word fluency task. The communicative impact of a word-finding problem and need for discourse level study are discussed. PMID- 8216966 TI - Adult age differences in forgetting sentences. AB - Age comparisons of performance-based measures of forgetting were carried out. In Exp. 1, 18- to 21-year-olds and 55- to 64-year-olds (n = 24) forgot at an equal rate when compared at 30 s and at 3, 6, and 24 hr after acquisition. In Exp. 2, 17- to 21-year-olds and 65- to 74-year-olds (n = 24) were compared at the same 4 retention intervals. Initial learning was equated for the 2 groups. There was evidence for an age difference in forgetting rate in cued recall when a minimal learning level was required. In Exp. 3, 440 men and women 17 to 74 years old were assigned to a retention interval from 10 min to 7 hr. Age was related to 4 performance-based measures of forgetting rate. Although the age differences were small, they imply 2 decremental processes: 1 before 10 min, possibly a result of incomplete consolidation, and a later 1 that is continuously and cumulatively operative thereafter. Evidence relating initial level to forgetting rate is presented. PMID- 8216967 TI - Dysfunctional beliefs and attitudes about sleep among older adults with and without insomnia complaints. AB - This study examined the beliefs and attitudes about sleep among 145 older adults. Ss were either chronic insomniacs (n = 74) or self-defined good sleepers (n = 71). They rated their level of agreement or disagreement (visual analog scale) with 28 statements tapping various beliefs, expectations, and attributions about several sleep-related themes. The results showed that insomniacs endorsed stronger beliefs about the negative consequences of insomnia, expressed more hopelessness about the fear of losing control of their sleep, and more helplessness about its unpredictability. These findings suggest that some beliefs and attitudes about sleep may be instrumental in perpetuating insomnia. The main clinical implication is that these cognitions should be identified and targeted for alteration in the management of late-life insomnia. PMID- 8216968 TI - Characterization of particle- and vapor-phase organic fraction emissions from a heavy-duty diesel engine equipped with a particle trap and regeneration controls. AB - The effects of a ceramic particle trap on the chemical and biological character of the exhaust from a heavy-duty diesel engine have been studied during steady state operation and during periods of trap regeneration. Phase I of this project involved developing and refining the methods using a Caterpillar 3208 engine, and Phase II involved more detailed experiments with a Cummins LTA10-300 engine, which met Federal 1988 particulate matter standards, and a ceramic particle trap with built-in regeneration controls. During the Phase I experiments, samples wee collected at the Environmental Protection Agency (EPA)* steady-state mode 4 (50% load at intermediate speed). Varying the dilution ratio to obtain a constant filter-face temperature resulted in less variability in total particulate matter (TPM), particle-associated soluble organic fraction (SOF), solids (SOL), and polynuclear aromatic hydrocarbon (PAH) levels than sampling with a constant dilution ratio and allowing filter-face temperature to vary. A modified microsuspension Ames assay detected mutagenicity in the SOF samples, and in the semivolatile organic fraction extracted from XAD-2 resin (XAD-2 resin organic component, XOC) with at least 10 times less sample mass than the standard plate incorporation assay. Measurement techniques for PAH and nitro-PAH in the SOF and XOC also were developed during this portion of the project. For the Phase II work, two EPA steady-state rated speed modes were selected: mode 11 (25% load) and mode 9 (75% load). With or without the trap, filter-face temperatures were kept at 45 degrees +/- 2 degrees C, nitrogen dioxide (NO2) levels less than 5 parts per million (ppm), and sampling times less than 60 minutes. Particle sizes were determined using an electrical aerosol analyzer. Similar sampling methods were used when the trap was regenerated, except that a separate dilution tunnel and sampling system was designed and built to collect all of the regeneration emissions. The SOF and XOC were extracted from their collection media with dichloromethane. Levels of 12 PAH and nitro-PAH compounds with known biological effects were determined using high-pressure liquid chromatography with fluorescence detection. Two additional dinitro-PAHs were analyzed semi quantitatively, and several representative SOF and XOC samples were screened for three additional PAH compounds. Mutagenicity was assessed using the modified Ames microsuspension assay.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8216969 TI - Measurements of ventilation in freely ranging subjects. AB - Both the level of ventilation and breathing pattern (breathing frequency, inspiratory time, and tidal volume) have an important influence on particle deposition and gas uptake in the lungs. Accordingly, a description of these measures is needed to assess better the dose of particulate deposit and gas uptake in the lungs during varied activities. The long-term objectives of this study were to develop a means of measuring minute ventilation in the field by using body surface displacements, and to evaluate the utility of heart rate as an index of minute ventilation. By using respiratory inductance plethysmographic belts and magnetometers placed on the rib cage and abdomen, ventilation and breathing pattern can be noninvasively measured in mobile individuals. Our specific aims were (1) to validate measurements of ventilation using body surface displacement; (2) to describe breathing patterns in subjects performing a variety of daily activities in the laboratory; (3) to analyze relationships between minute ventilation and heart rate; and (4) to measure ventilation in the field with one technique utilizing body surface displacements and another based upon heart rate. We found that values of tidal volume, inspiratory time, and breathing frequency derived from body surface displacement measurements correlated well with those determined spirometrically during a variety of activities. The coefficient of determination for tidal volume was 0.97 +/- 0.2 for cycling, 0.93 +/- 0.07 for arm cranking, 0.91 +/- 0.05 for pulling, and 0.84 +/- 0.12 for lifting. Our experiments showed that the breathing pattern was altered by the use of a mouthpiece and varied according to the type of activity. The use of a mouthpiece increased tidal volume by 34%, decreased the breathing frequency by 10%, and increased minute ventilation by 16%. There was more variability of these parameters during lifting and pulling activities than during cycling. The ventilation-heart rate relationship varied from subject to subject and was altered by the use of a mouthpiece. We found that ventilation measured in the field from body surface displacement correlated well with ventilation measured using the pneumotachograph (R2 = 0.89). However, measurements of ventilation derived from heart rate were not as accurate as those derived from body surface displacements. We concluded that minute ventilation can be measured accurately using body surface displacements in the laboratory and in the field. Heart rate can also be utilized, but factors affecting the minute ventilation-heart rate relationship, such as the use of a mouthpiece and range of heart rate, must be addressed to obtain more accurate estimates of minute ventilation. PMID- 8216970 TI - Assessment of heart rate as a predictor of ventilation. AB - The rate of ventilation and route of breathing (i.e., nasal versus oronasal) are potential determinants of pollutant doses to target sites in the lung. However, the lack of accurate methods for ambulatory measurement of ventilation has hindered estimation of exposure and dose in freely ranging individuals, complicating the interpretation of the relationships among exposure, dose, and response in epidemiological studies. The goal of this project was to develop and validate a method of monitoring ventilation for large-scale epidemiologic investigations. We estimated ventilation for individual subjects from ambulatory heart rate monitoring, using the relationship between ventilation and heart rate that had been obtained during exercise testing. Fifty-eight subjects participated in the study, which included healthy adults and children, and subjects with lung and heart disease. Subjects performed cycle exercise and tasks involving lifting and vacuuming. Work loads of progressive and variable order were used in the testing. Conventional methods were used to measure heart rate and total ventilation, and a sampling mask was developed to measure the partitioning of breathing between oral and nasal routes. The minute ventilation-heart rate relation was evaluated under steady-state and varying work loads. In a second phase, subjects wore wristwatch monitors that recorded their heart rates, minute by minute, throughout the day. Subjects recorded activities, locations, and levels of exertion. Two 16-hour monitoring periods were obtained from each subject. The laboratory findings documented considerable intersubject variability in the minute ventilation-heart rate relation with a two- to five-fold range in the coefficients describing the change in ventilation relative to heart rate. This variation implies that individual testing is required to derive accurate predictive equations. Minute ventilation-heart rate regressions for the maximal progressive exercise test and for the test with a nonprogressive submaximal work load sequence were comparable, indicating that varying the sequence of work loads does not substantially affect the minute ventilation-to-heart rate ratio. During upper body work (e.g., lifting), the minute ventilation-to-heart rate ratio was one-third greater than during lower body exercise. Diverse patterns of partitioning breathing between oral and nasal routes were observed with increasing oral ventilation in most subjects as work load increased. In the field, heart rate and activity patterns were monitored successfully in adults and children with low rates of instrument failure and noncompliance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8216971 TI - Failure of ozone and nitrogen dioxide to enhance lung tumor development in hamsters. AB - We tested the hypothesis that the two common oxidant air pollutants, ozone and nitrogen dioxide, modulate the development of respiratory tract tumors in Syrian golden hamsters. The animals received subcutaneous injections of the carcinogen diethylnitrosamine (20 mg/kg) twice a week while being exposed continuously to an atmosphere of 0.8 parts per million (ppm)* of ozone or 15 ppm of nitrogen dioxide. Animals were killed 16 weeks or 24 to 32 weeks after the beginning of the treatment. Ozone delayed the appearance of tracheal tumors and reduced the incidence of tumors in the lung periphery. A suspected neuroendocrine differentiation of those lung tumors could not be established by immunocytochemistry due to overfixation of tissues. On the other hand, ozone seemed to mitigate development of hepatotoxic lesions mediated by diethylnitrosamine. In animals treated with diethylnitrosamine and exposed to nitrogen dioxide, fewer tracheal tumors and no lung tumors were found. Only a few lung tumors were produced in animals treated with diethylnitrosamine and kept in an atmosphere of 65% oxygen. The previously observed neuroendocrine nature of tumors induced by simultaneous exposure to diethylnitrosamine and hyperoxia could not be established because the long fixation of tissues precluded immunocytochemical stains. Animals treated with diethylnitrosamine and kept in filtered air while being housed in wire-mesh cages developed fewer lung tumors than animals given the same treatment and kept on conventional bedding in shoebox cages. Although all inhalants tested are known to produce substantial cell proliferation in the respiratory tract, it was not possible to document whether this would enhance lung tumor development. The role of the two common air pollutants, ozone and nitrogen dioxide, as possible additional risks in the pathogenesis of lung cancer in animals continues to remain uncertain. PMID- 8216972 TI - Cytokine network and acute primary HIV-1 infection. AB - OBJECTIVE: To investigate the relationship between cytokine serum levels, peripheral blood lymphocyte subsets and clinical picture in acute primary HIV-1 infection. PATIENTS AND METHODS: Absolute number/microliters total lymphocytes, CD4+, CD8+ and natural killer (NK) cells, as well as serum levels of soluble CD8 receptor, interleukin (IL)-1 beta, IL-2, IL-4, IL-6, tumour necrosis factor (TNF) alpha, interferon (IFN)-gamma, beta 2-microglobulin and 5'-neopterin were determined in 15 patients with acute primary HIV-1 infection, 16 asymptomatic HIV 1-seropositive individuals and 18 HIV-1-seronegative individuals at risk for HIV 1 infection. RESULTS: Acute primary HIV-1 infection was characterized by significant CD4+ lymphocytopenia with low IL-2 serum concentrations, and by high absolute number of circulating CD8+ and NK cells, with elevated serum levels of soluble CD8 receptor, IL-1 beta, IFN-gamma and 5'-neopterin. Follow-up of acute seroconverters showed a significant decrease in NK cell counts and IL-1 beta levels, with an increase of IL-6. CONCLUSIONS: In acute primary HIV-1 infection, significant alteration of cytokine release, possibly induced by viral antigens, could be responsible for both clinical picture and activation of cytotoxic cells through abnormal mechanisms. PMID- 8216973 TI - Virus isolation and quinolinic acid in primary and chronic simian immunodeficiency virus infection. AB - OBJECTIVE: In this 2.5-year study of simian immunodeficiency virus (SIVsm) infection in rhesus monkeys, quinolinic acid (QUIN) levels and virus isolation determinations were made in serial cerebrospinal fluid (CSF) and blood samples to evaluate the relationship between these parameters over the course of infection. METHODS: Eight rhesus monkeys were inoculated in the saphenous vein with SIVsm. Four animals were maintained as uninoculated controls. CSF and blood samples were obtained every 1-4 weeks over the course of study. SIV isolation was determined in H9 cells for the CSF and in primary rhesus lymphocyte co-cultures for peripheral blood mononuclear cells (PBMC). QUIN was quantitated in CSF and serum by electron-capture negative chemical ionization gas chromatography mass spectrometry. RESULTS: All SIV-inoculated animals became CSF and PBMC isolation positive by 1-3 weeks post-inoculation. Control animals remained SIV-negative. One SIV-positive animal was humanely euthanized at 2 weeks post-inoculation. The three SIV-inoculated animals that were CSF isolation-negative after the fifth week post-inoculation maintained CSF QUIN values < 100 nM, remained CSF and PBMC isolation-negative, and clinically healthy in the chronic course of disease. In contrast, the four SIV-inoculated animals that were CSF isolation-positive 6-8 weeks post-inoculation had CSF QUIN levels as high as 153-565 nM during the second month post-inoculation and remained CSF virus isolation-negative, persistently PBMC isolation-positive, and experienced clinical symptoms of SIV in the chronic course of disease. Three of these four animals have succumbed to SIV infection. DISCUSSION: Initial QUIN responses and viral isolation status in the first month post-inoculation were consistent among SIV-inoculated animals with CSF and serum QUIN values significantly higher than those of controls. A divergence within the SIV-inoculated group of animals became apparent within the second month of primary SIV infection and was maintained throughout the course of infection. Persistent PBMC viral isolation and marked elevations of QUIN were linked to symptomatic disease and a poor prognosis for survival. Predominantly negative PBMC viral isolation and slight, but significant, elevations of QUIN were linked to asymptomatic disease with a favorable prognosis for survival. PMID- 8216974 TI - Characterization of dual HIV-1 and HIV-2 serological profiles by polymerase chain reaction. AB - OBJECTIVE: To evaluate the frequency of dual HIV-1 and HIV-2 DNA sequences in patients with dual serological profiles. DESIGN: We tested 40 samples from AIDS patients living in Abidjan, Cote d'Ivoire. METHODS: Dual serological reactivity was determined by double Western blot and two enzyme-linked immunosorbent assays with recombinant proteins and synthetic peptides as antigens. The Western blot was considered to show dual reactivity when sera reacted with at least two glycoproteins and one core protein of each virus. HIV DNA sequences were detected by hybridization to radiolabelled probes of polymerase chain reaction (PCR) products amplified using specific primers. RESULTS: Both HIV-1 and HIV-2 DNA sequences were detected in four out of 11 samples with a dual serological profile and in four out of 24 samples with anti-HIV-1 antibodies only. CONCLUSION: These results show that dual HIV-1 and HIV-2 serological profiles are not always due to infection by both viruses, and emphasize the need for a combination of serological and PCR assays for the appraisal of these viral infections. PMID- 8216975 TI - Genetic heterogeneity of the V3 region of the HIV-1 envelope glycoprotein in Brazil. Brazilian Collaborative AIDS Research Group. AB - OBJECTIVE: To examine the genetic heterogeneity of the V3 region of HIV-1 gp120 from 22 Brazilian HIV-1 specimens. DESIGN: Genetic heterogeneity was examined by DNA sequencing of the C2 V3 region of the HIV-1 envelope (env) gene from polymerase chain reaction (PCR)-amplified HIV-1 DNA. Deduced amino-acid sequences were compared to determine the extent of amino-acid conservation among the Brazilian specimens. Genetic similarity among and between the Brazilian specimens and other previously published HIV-1 isolates was analyzed by principal co ordinate and DNA parsimony methods. METHODS: A 282 base pair (bp) region of a 1.5 kilo (k) bp PCR-amplified HIV-1 env fragment was sequenced by a Taq dye-labeled primer cycle sequencing reaction. Nucleotide sequences were used to analyze inter specimen relationships based on overall nucleotide sequence similarity and DNA parsimony principles. RESULTS: Amino-acid comparison showed that 15 of the 35 (43%) residues of the V3 loop were conserved among the Brazilian specimens. Nine of the 22 (40%) Brazilian specimens contained the North American-European GPGR tetrapeptide motif, while eight (36%) contained the GWGR motif, previously reported in Japanese isolates. Principal co-ordinate analysis demonstrated that 19 of the 20 examined Brazilian HIV-1 specimens were more similar to North American and Haitian isolates than to African isolates. Similar results were also obtained by DNA parsimony analysis. CONCLUSION: The majority of the Brazilian specimens examined are more genetically related to North American and Haitian HIV 1 isolates than to African isolates. This finding and the presence of a GWGR V3 loop motif in some Brazilian isolates may be important for vaccine development. PMID- 8216976 TI - Diversity of the V3 region of HIV in Paris, France. AB - OBJECTIVE: To carry out, within France, a large-scale molecular epidemiological investigation on the principal neutralizing determinant of HIV-1, located in the third variable region (V3) of the envelope protein. Such investigations are of the utmost importance in the identification and monitoring of the distribution and spread of different viral strains internationally. DESIGN: Using polymerase chain reaction (PCR), we examined the genetic variation of the V3 region sequences of 28 HIV-infected patients from Paris, France. RESULTS: Comparison of the Parisian V3 loop sequences with other published data indicates that the range of diversity in France is included within that of a large group that contains sequences from North America, the rest of Europe, Japan, India and Africa. Variability appears to be lower in the V3 loop than in its flanking regions. Five out of the six putative N-linked glycosylation sites show preferential alterations to charged amino acids. We report two motifs at the tip of the loop that have not been described previously. CONCLUSIONS: The structural homogeneity and the wide geographic representation of the major V3 group suggests that a common strategy could be applied to a large proportion of isolates in the development of a broad-spectrum HIV vaccine. PMID- 8216977 TI - Inactivation of HIV infectivity by the chlorite-oxygen reaction product tetrachlorodecaoxygen. AB - OBJECTIVE: Since the chlorite-oxygen reaction product tetrachlorodecaoxygen (TCDO) anion complex promotes efficaciously tissue repair and has antibacterial activity, our aim was to determine the effects of TCDO on the replication of HIV and on the infectivity of free HIV particles. DESIGN: The effects of TCDO on cellular HIV replication machinery and the consequences of TCDO for infectivity of HIV virions were evaluated. METHODS: Virus yields in supernatants of TCDO supplemented cultures of HIV-infected cells or virus infectivity in TCDO-treated virus stocks were quantified by titration assays and then calculating the 50% tissue culture infectious dose. RESULTS: First, TCDO did not affect the replication of HIV in persistently infected lymphocytic and monocytic cell lines or in peripheral blood mononuclear cells. Second, supplementation of HIV stocks with TCDO markedly decreased the infectivity of HIV particles in a concentration dependent manner. Third, the binding of gp120 envelope glycoprotein of HIV-1 to cells is blocked by pre-incubation with TCDO. Fourth, the inhibition of HIV replication by the reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine (zidovudine) in de novo infected cell cultures was not affected by the simultaneous addition of TCDO. However, the delayed virus spread of HIV in cultures in the presence of suboptimal concentrations of zidovudine could significantly be blocked by the simultaneous addition of TCDO. Fifth, TCDO failed to induce the chromosomally integrated HIV-1 provirus in the T-lymphoma cell line ACH2. CONCLUSIONS: TCDO appears to inactivate HIV particles directly, but has no influence on the intracellular replicative machinery of HIV. Our results suggest that a clinical evaluation of the TCDO complex as chemotherapy for HIV infection and full-blown AIDS should be considered, particularly in patients concomitantly receiving zidovudine. PMID- 8216978 TI - Clinical risk factors for malnutrition in HIV-1-infected patients. AB - OBJECTIVE: To estimate the influence of fever, diarrhoea, stage of HIV disease, opportunistic infection and anorexia on malnutrition in HIV-infected patients we analysed data of patients undergoing a nutritional counselling programme from November 1989 to April 1992. PATIENTS AND METHODS: Our study group comprised 104 HIV-infected patients (98 homosexual men, 15 asymptomatics, 30 AIDS-related complex patients, 59 AIDS patients). Nutritional status was measured by previous weight loss, bioelectrical impedance analysis and prospective intake protocol. RESULTS: Patients had lost 10 +/- 8.7% of body weight. Compared with controls, body mass index was lower (P < 0.001), and extracellular/body cell mass ratio (ECM/BCM) was higher (P < 0.001). BCM was reduced proportionately to weight loss, percentage of body fat was lower compared with controls (P < 0.001), even in patients with stable weight. Clinical risk factors for malnutrition were identified as fever in 31, diarrhoea in 26, acute infections in 42 and anorexia in 73 out of 104 patients. One single risk factor was predominant in 63 patients: fever in five, diarrhoea in 14, acute infections in 17 and anorexia in 27 patients. Weight loss was not linearly correlated to CD4 count or to time since AIDS diagnosis. Food intake was highly variable (39-165% of calculated needs) without correlation to weight loss. CONCLUSIONS: Loss of body fat was found even in the earlier stages of HIV infection and was more severe than loss of BCM. Important risk factors for malnutrition are anorexia (most frequent), diarrhoea and fever (most severe). Most patients have combined risk factors. Treatment strategies and pathophysiologic studies should consider the heterogeneity of HIV associated malnutrition. PMID- 8216979 TI - The value of wide-needle aspiration in the diagnosis of tuberculous lymphadenitis in Africa. AB - OBJECTIVES: To evaluate wide-needle (19-gauge) aspiration in the diagnosis of tuberculous lymphadenitis. SETTING: Department of Surgery, University Teaching Hospital, Lusaka, Zambia. PATIENTS: Three hundred and four patients presenting to one surgeon for diagnostic surgical biopsy of a peripheral lymph node during 1989 1990. DESIGN: Prospective study in which wide-needle aspiration routinely preceded open surgical biopsy. MAIN OUTCOME MEASURES: Histology and mycobacterial culture of the surgically biopsied lymph node; HIV-1 serology; successful aspiration of material, naked-eye appearance of aspirate, presence of acid-fast bacilli and/or microscopic caseation in the aspirate. RESULTS: One hundred and eighty-eight out of 304 (61.8%) patients had histologically and/or culture-proven tuberculous lymphadenitis, of whom 155 out of 183 (84.7%) tested HIV-1 seropositive. Material was successfully aspirated from 180 out of 188 (95.7%) of patients with proven tuberculous lymphadenitis. Macroscopic caseation, diagnosable on naked-eye examination alone of the aspirate, was present in 49 out of 120 (40.8%) consecutive aspirates from tuberculous nodes. Acid-fast bacilli and/or microscopic caseation were seen in 116 out of 155 (74.8%) aspirates from tuberculous nodes for which smears stained both by Ziehl-Nielsen and haematoxylin & eosin were available. CONCLUSIONS: It is recommended that all patients with suspected tuberculous lymphadenitis in Africa, undergo wide-needle aspiration before surgical biopsy or empirical treatment. PMID- 8216980 TI - Sociodemographics and HIV risk behaviors of bisexual men with AIDS: results from a multistate interview project. AB - OBJECTIVE: To describe the sociodemographic characteristics and sexual and drug use behaviors of men with AIDS who engage in bisexual activity. METHODS: We interviewed 2120 men aged > or = 18 years who were reported with AIDS in 11 states and cities. Men were considered bisexual if they reported having had sex with a man and a woman in the previous 5 years. RESULTS: Of the 2020 men with AIDS who reported being sexually active in the previous 5 years, 1150 (57%) had had male partners only, 522 (26%) had had female partners only and 348 (17%) had had both. White men were least likely to report bisexual behavior (15%; 161 out of 1071). Men of Latin American descent were most likely to report bisexual behavior (24%; 37 out of 155), especially those born outside the United States who had lived there for < or = 10 years (38%; 11 out of 29). Bisexual Latin American men, regardless of birthplace, were more likely to be currently married than all other bisexual men (22 versus 7%; P < 0.05). HIV risk behaviors differed between men reporting bisexual and those reporting exclusively homosexual or heterosexual activity. Injecting drug use in the previous 5 years was more common among bisexual than homosexual men (12 versus 6%; P < 0.05). Bisexual men were more likely (P < 0.05) to have received money for sex (11%) than homosexual (4%) or heterosexual men (4%). This difference was even greater among injecting drug users receiving money for sex: bisexual (29%), homosexual (13%), heterosexual (3%). CONCLUSIONS: Demographics and HIV risk behaviors of bisexual men with AIDS differ from those of homosexual and heterosexual men with AIDS. These findings indicate that special efforts are needed to prevent sexual transmission of HIV among bisexual men. PMID- 8216981 TI - HIV-1 infection in young men in northern Thailand. AB - OBJECTIVES: To determine risk factors for HIV-1 infection in young men in northern Thailand. METHODS: At enrollment into a prospective study, data were collected from a self-administered questionnaire and serologic testing on a cohort of 1115 young men selected by lottery for conscription. RESULTS: The overall HIV-1 infection rate was 6.9%; however, the rate was 15.3% among the 387 (34.7%) men who had been living in the upper north subregion of Thailand compared with 2.5% for the remaining 728 men (P < 0.001). A history of sex with female prostitutes was reported by 74.7% of men and increased frequency of this type of sex was highly associated with HIV-1 infection and a history of sexually transmitted disease (STD) symptoms (chi 2 for trend, P < 0.001). In stratified and multivariate analyses, however, history of STD symptoms, reported by 42.5% of the cohort, was most strongly associated with HIV-1 infection. Only 42.8% of men who reported sex with prostitutes had used condoms more than half the time. CONCLUSIONS: Young men in the general population in northern Thailand are at high risk for HIV-1 infection via sex with female prostitutes; STD are highly associated with HIV-1 infection. Increasing condom use and controlling STD should be immediate goals of HIV control programs. PMID- 8216982 TI - A clinical and pathological comparison of the WHO and CDC case definitions for AIDS in Kinshasa, Zaire: is passive surveillance valid? AB - OBJECTIVES: To compare the specificity of the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) case definitions for AIDS in autopsy cases from Zaire. SETTING: Mama Yemo Hospital and University Hospital morgues in Kinshasa, and Karawa Hospital in Equateur Region, Zaire. METHODS: Autopsy cases with a clinical diagnosis of AIDS on the death certificate or chart were studied. Evaluation included post-mortem HIV-1 serology, chart review for specific AIDS-related symptoms and signs, and application of WHO and CDC case criteria to the clinical and autopsy diagnoses. RESULTS: Of the 68 diagnosed AIDS cases, 98% fulfilled WHO criteria for AIDS and 93% fulfilled both WHO and CDC criteria. All cases fulfilling both criteria were HIV-1-seropositive. Opportunistic infections accounted for 84% of CDC AIDS-defining conditions. Disseminated tuberculosis was the most frequent (41%) specific diagnosis; Pneumocystis carinii pneumonia was rare (< 2%). CONCLUSIONS: There was good concordance between WHO and CDC case definitions. A diagnosis of AIDS on the chart or death certificate is adequate for surveillance purposes in this population. PMID- 8216983 TI - Heterosexual transmission of HIV in a cohort of couples in New York City. AB - OBJECTIVE: Since heterosexual transmission of HIV in the United States is occurring at an increasing rate, especially among black and Hispanic couples and those in which one member has a history of intravenous drug use, we sought to study the heterosexual transmission of HIV in couples. DESIGN: Multiple logistic regression analysis of risks for HIV infection in female partners. METHODS: We enrolled 158 non-intravenous drug user (IVDU) steady heterosexual partners of HIV infected individuals (indexes) in this study. Of these, 93% were women, 54% were Hispanic whites, 23% were black and 65.6% were partners of IVDU. RESULTS: In a multiple logistic regression analysis of risks for HIV infection in female partners, the strongest predictors of transmission were AIDS or AIDS-related complex (ARC) in the index [adjusted odds ratios (OR), 16.81; P < 0.001 and 12.53; P = 0.003, respectively], a history of anal intercourse (adjusted OR, 10.81; P < 0.001) and bleeding as a result of intercourse (adjusted OR, 4.90; P < 0.05). Female-to-male transmission was detected in seven out of 11 couples at risk. Ethnicity, number of episodes of vaginal intercourse, number of other sexual partners and history of sexually transmitted infections were not significantly associated with transmission to women. CONCLUSION: Our study demonstrates that health of the index, anal intercourse and bleeding as a result of intercourse are the major determinants of sexual transmission of HIV to women in couples. PMID- 8216984 TI - The utility of verbal autopsies for identifying HIV-1-related deaths in Haitian children. AB - OBJECTIVE: To determine whether deaths among Haitian infants born to HIV-1 seronegative women could be distinguished from deaths among children born to HIV 1-seropositive women using the verbal autopsy technique. METHODS: Mothers of 315 Haitian children who died were interviewed about events leading to the child's death. Three physicians independently reviewed interview data and determined the probable cause of death without knowledge of maternal HIV-1 status or hospital records. The underlying causes of death assigned to the infants were analyzed to determine whether maternal HIV status could be predicted. RESULTS: There was good agreement among the physicians (kappa = 0.62) and 90% agreement between hospital records and the verbal autopsy diagnosis. Compared with children born to HIV-1 seronegative women, deaths in children born to HIV-1-seropositive mothers were more likely to be ascribed to a presumptive diagnosis of AIDS (37 versus 21%; P = 0.01). The sensitivity and specificity of verbal autopsies for identifying deaths associated with maternal HIV-1 infection ranged from 37 to 59% and from 69 to 79%, respectively, depending on the classification system used. The predictive positive value of a death believed to be consistent with pediatric HIV-1 infection was 26-30% and the predictive negative value was 85-90%. CONCLUSION: Verbal autopsies may be useful for distinguishing certain causes of death, but have limited utility for distinguishing deaths associated with maternal HIV-1 infection from deaths among children born to HIV-1-seronegative women. PMID- 8216985 TI - Temporary expatriation is related to HIV-1 infection in rural Senegal. AB - OBJECTIVES: To assess temporary expatriation as a risk factor for HIV infection in a rural area of Senegal and to examine the transmission of HIV from expatriates to their families. DESIGN: Cross-sectional study in identified expatriates and in a representative cluster sample of the general population from the same geographical area in northern Senegal. METHODS: In 1989, a survey (including questionnaire and serological tests for HIV-1 and HIV-2) was conducted in all expatriates currently living in 11 villages in northern Senegal and spouses of all expatriates (present or not) from this area ('expatriate' group, n = 258). In parallel, a cluster sample of 600 adults was drawn from eight villages of the same area, of whom 414 were selected as the control group since they and their spouses had not travelled outside Senegal in the last 10 years. RESULTS: In the 'expatriate' group, sera from 39 subjects were confirmed as HIV-positive by Western blot [17 out of 63 men (27.0%) and 22 out of 195 women (11.3%)]. Of these subjects, 33 were infected by HIV-1, four by HIV-2 and two had a dual HIV-1/2 profile. In contrast, only two subjects (one man and one woman) from the control group were infected by HIV-2 and none by HIV-1. In men, HIV-1 seroprevalence was associated with age < 40 years [odds ratio (OR), 7.4; P = 0.03] and previous sexually transmitted disease (STD) symptoms (OR, 13.5; P = 0.03), whereas the risk factors in women were age < 25 years (OR, 3.7; P = 0.04), being a widow (OR, 30.4; P < 0.01) and presence of sexual activity over the last 2 years (OR, 21.3; P < 0.01). CONCLUSIONS: Penetration of HIV-1 infection in a country where HIV-2 is endemic shows that the HIV-1 epidemic is currently spreading to rural West Africa. Migrant workers appear to play a major role in this epidemic. PMID- 8216986 TI - Research on bisexual men: sociodemographic or social context? PMID- 8216987 TI - Long-term survival among HIV-1-infected prostitutes. PMID- 8216988 TI - Modified nested polymerase chain reaction for the detection of HIV-1 infection in children. PMID- 8216989 TI - CD4+ lymphocytopenia in HIV-seronegative homosexual men. PMID- 8216990 TI - The cause of elevated glycosylated haemoglobin concentrations in AIDS. PMID- 8216991 TI - Old plague, new plague, and a treatment for both? PMID- 8216992 TI - Second anonymous HIV surveillance in Saughton Prison, Edinburgh: prisoners give a lead to other heterosexuals on being HIV tested. PMID- 8216993 TI - Successful treatment of cryptosporidiosis in an AIDS patient with letrazuril. PMID- 8216994 TI - Pulmonary malacoplakia in AIDS. PMID- 8216995 TI - Transfusion-associated diffuse cytomegalovirus enterocolitis and small-bowel perforation in a patient with AIDS. PMID- 8216996 TI - Scopulariopsis brevicaulis skin lesions in an AIDS patient. PMID- 8216997 TI - Reported and expected AIDS cases in Kabarole District, Western Uganda, 1991 and 1992. PMID- 8216998 TI - Statistics from the World Health Organization and the Centers for Disease Control and Prevention. PMID- 8216999 TI - Cat scratch disease. PMID- 8217000 TI - Pediatric odontogenic infections. PMID- 8217002 TI - Lung abscesses and pleural empyema in children. PMID- 8217001 TI - The acquired immunodeficiency syndrome (AIDS) in African children. PMID- 8217003 TI - Protozoal infections of the intestinal tract in children. PMID- 8217004 TI - Childhood tuberculosis. AB - The dramatic resurgence and increase in the total number of cases of tuberculous infection and disease in children is alarming in the United States. With poverty, poor access to health care, overcrowding (predominantly in inner-city areas), and an increase in immigration from areas with high endemic rates of tuberculosis, the problem in children will continue to increase. If the impact of coinfection with HIV and M. tuberculosis becomes significant, as it has in adults in the United States, this increase in the total number of cases of tuberculous disease could be staggering. The impact of multiple drug-resistant strains of M. tuberculosis and the current crises in availability of effective antituberculous drugs will need to undergo basic and clinical research. Although the possibility for eradication of M. tuberculosis as a human pathogen in the United States still exists, clinicians must reeducate themselves regarding the epidemiology, pathophysiology, diagnostic work-up, and effective treatment of children with tuberculosis in the current situation of increasing tuberculous disease and resistant organisms in children. PMID- 8217005 TI - Clinical manifestations and treatment of pulmonary infections in cystic fibrosis. PMID- 8217006 TI - Hepatitis C. PMID- 8217007 TI - New tests for the rapid diagnosis of infection in children. AB - The development of new and more rapid methods by which to diagnose infectious diseases has just begun. Although many assays for the rapid detection of important pediatric pathogens are widely available now, new and improved assays continue to be created and marketed. It is clear that rapid diagnosis will become increasingly available to pediatricians and will assist in the diagnosis and treatment of infections in children. PMID- 8217008 TI - Cultural diversity in nursing care: the lesbian, gay, or bisexual client. AB - This paper examines the gay, lesbian, and bisexual persons as subcultures of the dominant Anglo-American culture in the United States of America in relation to influences on their access to and use of health care systems and resources. Nurses need to be aware of the unique health needs of such clients, and examine their own cultural belief systems about same-sex relationships. Negative attitudes or misinformation can lead to poor quality of care and disrupt nurse client relationships. PMID- 8217009 TI - International Council of Nursing and Transcultural Nursing Society: alike or different? PMID- 8217010 TI - Gadsup of Papua New Guinea revisited: a three decade view. AB - The purpose of this article is to share some highlights of the author's revisits to Papua New Guinea covering three decades (1962-1992) with focus on the Gadsup of the Eastern Highlands of New Guinea. In addition, some recent developments in the country are covered as well as special visits with members of the Papua New Guinea Nurses Association. A comparative analysis of the world view, social structure, and related factors is made with respect to the theory of Culture Care Diversity and Univers-ality with two Gadsup villages. In general, the researcher found limited progress and beneficial health care changes in the two villages. Rascalism with violence was discovered which had cultural functions to redress some of the socioeconomic inequities and dissatisfactions of the indigenous people. Major tenets of the Culture Care theory were supported with the Gadsup, especially related to diverse forms, meanings, and lifestyle processes. PMID- 8217011 TI - Transcultural nursing clinical field study incidents: What do you think? What would you do? PMID- 8217012 TI - Transcultural nursing: facing the challenges of advocacy and diversity/universality. AB - This paper is in response to an invitation to address the topic of advocacy and diversity from the perspective of past and present transcultural nursing. With origins in nursing, with its philosophy of active intervention, and in anthropology, where relativism proposes merit in diverse (including non interventive) approaches to health and illness, transcultural nursing grapples with potential epistemological conflict as it helps shape health care in highly industrialized, multicultural societies and even more varied global contexts. As a developing subdiscipline, transcultural nursing continuously reexamines dialectical relationships between change and preservation and between health care needs and the risk of imposition. Whereas advocacy is viewed as a moral imperative in nursing, diversity (which can be used to argue against acknowledgement of differences and to promote the pretense that everything is the same for everyone) remains better developed conceptually than operationally, while universality too often falls prey to misuse as an argument against acknowledgement of diversity. Within a framework constructed from the juxtaposition of advocacy with diversity/universality (Leininger, 1988c, 1991), this article appraises the accomplishments and challenges of transcultural nursing as it moves into its second quarter century. It is proposed that the future of transcultural nursing should emphasize development of realistic nursing roles that include a confluence of advocacy and diversity/universality and negotiation of responsible social conceptualizations of cultural issues such as "race" and diversity. PMID- 8217013 TI - Structure of bis[cis-1,2-bis(diphenylphosphino)ethylene] dichlororhenium(II) hexane solvate. AB - [ReCl2(C26H22P2)2].C6H14 (I), M(r) = 1136.11, monoclinic, P2(1)/c, a = 11.426 (2), b = 13.078 (2), c = 17.323 (3) A, beta = 95.27 (1) degrees, V = 2577.7 (6) A3, Z = 2, Dx = 1.46 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 26.5 cm-1, F(000) = 1150, T = 296 K, R = 0.034 for 3269 [Fo2 > 3 sigma(Fo2)] reflections. The Re atom in (I) is located on an inversion point, fixed at the origin. One Cl and a complete tertiary phosphine ligand (Ph2PCHCHPPh2) are situated around the Re atom so as to generate a pseudo-octahedral geometry with a P1--Re--P2 angle of 79.07 (5) degrees and P1--Re--P2' angle of 100.93 (5) degrees. The Re--Cl, Re--P1 and Re--P2 distances are 2.432 (2), 2.401 (2) and 2.398 (2) A, respectively. Bond distances and angles for the phenyl rings range from 1.34 (1) to 1.41 (1) A and 117.4 (6) to 122.0 (7) degrees with averages of 1.38 (1) A and 120.0 (1) degrees, respectively. PMID- 8217014 TI - Structure of tetraaquacalcium perbromate. AB - The structure of the title compound consists of columns of Ca ions surrounded by four columns of perbromate ions and four columns of water molecules alternating in pairs. The CaO8 complex was found to be dimensionally similar to corresponding complexes in other simple tetrahydrated calcium salts. The eight coordinating O atoms form a polyhedron which departs only slightly from a (distorted) square antiprism. Each of the crystallographically inequivalent perbromate ions was found to conform to rigid-body behavior while the CaO8 complex did not. Although the perbromate ions depart moderately from regular tetrahedral geometry, the mean Br--O bond length agrees well with previously determined values. Hydrogen bonds in this structure involve water-oxygen acceptors as well as perbromate-oxygen acceptors. PMID- 8217015 TI - (R)-2-hydroxy-3-iodo-2-methylpropyl 4-nitrobenzenesulfonate. AB - The global minimum conformation, as computed by PCMODEL [Gajewski & Gilbert (1992). Serena Software, Bloomington, IN, USA], of the title compound agrees with that observed in the crystal. In the crystal, the torsion angles I--CH2--C--CH2O, ICH2--C--CH2--O, C--CH2--O--S and CH2--O--S--C are -57.7 (4), -61.7 (4), 171.2 (2) and -73.0 (3) degrees, respectively. Weak intermolecular hydrogen bonding connects OO--H and OS = O with an O ... O distance of 2.927 (4) A and an angle about the H atom of 165 (4) degrees. PMID- 8217016 TI - Structure of Boc-Phe-D-Leu-Thr-OMe. AB - The X-ray crystal structure analysis shows that tert-butoxycarbonyl-L phenylalanyl-D-leucine-L-threonine methyl ester takes an open conformation in which the tert-butoxycarbonyl group is located face-to-face with the D-leucine isobutyl side chain. In the crystal, the molecules, translated by twofold screw symmetry, form an infinite sheet structure through four independent hydrogen bonds. PMID- 8217017 TI - Structure and absolute configuration of a high affinity 5-HT3 receptor antagonist, (5aS,9aS)-N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-2-chloro- 5a,6,7,8,9,9a-hexahydro-4-dibenzofurancarboxamide hydrochloride. AB - The absolute configuration was established as (S,S,S) by the R-factor test and by careful measurement of 197 enantiomorph-sensitive Friedel pairs of reflections. The determination also confirms the absolute stereochemistry of (-)-3 aminoquinuclidine, a compound used in the preparation of the title material. The cyclohexane/tetrahydrofuran ring fusion is cis. The quinuclidine moiety has almost perfect threefold symmetry; the front and rear halves are twisted about this axis by 15 degrees. Quinuclidine-N--H ... Cl- and amide-N--H ... Cl- hydrogen bonds link screw-dyad-related molecules along the b axis. PMID- 8217018 TI - Isostructural trigonal-bipyramidal CuII and nominally 1% CuII-doped ZnII complexes with N5 ligation. AB - [Cu(C6H18N4)(C10H10N2)](ClO4)2, (1-benzylimidazole)[N,N-bis(2-aminoethyl)-1,2 ethanediamine]copper(II) diperchlorate (1), M(r) = 566.88, monoclinic, P2(1)/c, a = 10.549 (1), b = 9.2465 (9), c = 25.256 (2) A, beta = 101.42 (1) degrees, V = 2415 (1) A3, Z = 4, Dm = 1.54 (1), Dx = 1.559 Mg m-3, lambda (Mo K alpha) = 0.71073 A, mu = 1.18 mm-1, F(000) = 1172, T = 296 (1) K, R = 0.048, wR = 0.069 for 3063 reflections. [Zn0.99Cu0.01(C6H18N4)(C10H10N2)](ClO4)2, 1% CuII-doped (1 benzylimidazole)[N,N-bis(2-aminoethyl)-1,2-ethanediamine]zinc(II) diperchlorate (2), M(r) = 568.72, monoclinic, P2(1)/c, a = 10.708 (1), b = 9.229 (2), c = 25.205 (2) A, beta = 101.867 (8) degrees, V = 2438 (1) A3, Z = 4, Dm = 1.54 (1), Dx = 1.549, lambda (Mo K alpha) = 0.71073 A, mu = 1.30 mm-1, F(000) = 1176, T = 295 (1) K, R = 0.041, wR = 0.055 for 3282 reflections. The isostructural distorted trigonalbipyramidal MN5 cations are separated by perchlorate anions. Equatorial M--N distances are similar in both cations [range 2.083 (3) to 2.105 (3) A for (1); 2.073 (3) to 2.084 (3) A for (2)]. In contrast, the axial M--N distances differ substantially [2.043 (3) and 1.971 (3) A for (1); 2.255 (4) and 2.054 (3) A for (2)]. Axial contraction in the copper complex (1) is consistent with a dz2 ground state. PMID- 8217019 TI - Structure of the product from a novel cyclization reaction involving a C(6) substituted uridine analog. AB - 5,6,7,7a,9,10,14b,14c-Octahydro-4-[2,3-O-(1-methylethylidene )-beta-D- ribofuranosyl]cyclopenta-[4,5]pyrimido[5',4':3,4]pyrrolo[2,1- a]isoquinoline 1,3(2H,4H)-dione, C25H31N3O6, M(r) = 469.54, tetragonal, P4(3)2(1)2, a = 12.577 (2), b = 12.577 (2), c = 29.893 (4) A, V = 4729 (1) A3, Z = 8, Dx = 1.319 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu = 7.9 cm-1, F(000) = 2000, T = 298 K, final R = 0.038, wR = 0.064 for all 1884 independent reflections and 432 variables. The crystal structure shows a syn conformation around the N(1)--C(1') single bond, consistent with other C(6)-substituted uridine analogs, and an unusual O(1') endo conformation of the ribose ring. The stereochemistries of the three newly created chiral centers are 14cR, 4aR, 7aS. PMID- 8217020 TI - Structure of a 2-arylquinoline dimer, a compound with a new ring system. AB - The title compound, 6,15-dimethyltribenzo-[c,f,j]naphtho[1,2,3,4-lmn][2,7]phe nanthroline was obtained in low yield from the reaction of 2-(4 methylphenyl)quinoline and various aryllithiums. The compound is a 'dimer' in which two phenylquinoline units are joined by three bonds; the dimer has exact twofold symmetry. Non-bonded interactions produce substantial out-of-plane distortions. Bond lengths between the two phenylquinoline halves suggest that the two phenylquinoline pi-electron systems are more-or-less undisturbed and linked by single bonds. Molecular-mechanics optimizations of models with inversion (1) and twofold symmetry suggest that the latter conformation is the more stable of the two to a slight extent. PMID- 8217021 TI - Structure of 2-methoxycarbonyl-1,4-dinitrocubane. AB - The title compound, methyl 2,7-dinitropentacyclo [4.2.0.0(2,5).0(3,8).0(4,7)]octane-1-carboxy late, is one of the few examples of cubanes with substituents on adjacent C atoms. There are two enantiomeric molecules per asymmetric unit in a structure with a noncentrosymmetric space group, P2(1)2(1)2. The molecules differ primarily in the conformations of the C NO2 groups adjacent to the methoxycarbonyl sustituents. The 1,2-disubstituted cubane C-C bonds average 1.564 A, a typical value for an unsubstituted cubane bond. PMID- 8217022 TI - Structures of 3-hydroxy-1-(2-methoxyethyl)-2-methyl-4-pyridinone, its hydrochloride and 1-ethyl-3-hydroxy-2-methyl-4-pyridinone hydrochloride hydrate. AB - 3-Hydroxy-1-(2-methoxyethyl)-2-methyl-4(1H)-pyridinone (1) exists mainly in the quinoid form with a small contribution from the aromatic zwitterion form, while 3 hydroxy-1-(2-methoxyethyl)-2-methyl-4(1H)-pyridinone hydrochloride (2) and 1 ethyl-3-hydroxy-2-methyl-4(1H)-pyridinone hydrochloride hydrate (3) are observed to occur in the aromatic form with a minor contribution from the quinoid resonance form. Different substituents at the ring N position do not have significant geometric effects in either the neutral molecules, as a group, or in the hydrochloride salts. PMID- 8217023 TI - Structure of a 1:1 complex between L-Asp-L-Phe and L-His-Gly. AB - Both molecules occur in slightly folded conformations, characterized by phi 2 = 93.7 degrees in L-His-Gly and an unusual phi 2 = 60.2 degrees in L-Asp-L-Phe. The peptide linkage of L-His-Gly displays a substantial deviation from planarity with omega 1 = -163.5 degrees. The crystal packing is arranged in thick hydrophilic layers separated by hydrophobic sheets composed of L-Phe aromatic side chains. There are numerous hydrogen bonds, including an extremely short contact [O...N = 2.532 (6) A] between the ionized L-Asp and L-His side chains. PMID- 8217024 TI - Hexamethylenetetramine at 298 K: new refinements. AB - New refinements of the crystal structure of hexamethylenetetramine (HMT, C6H12N4) have been carried out using previously reported neutron and X-ray diffraction data collected at 298 K. A new feature in the structure model is the inclusion of third-order Gram-Charlier coefficients for the description of the anharmonic C-H bond stretching, which is found to be significant. The charge-density distribution is analyzed in terms of the pseudoatom model of Stewart [Acta Cryst. (1976). A32, 565-574]. Our experimental determination of the molecular octapole moment gives = +1.0 (3)/e/ A3. The refinement involving HMT provides a worst-case example of a general deficiency in the application of the multipole model to noncentrosymmetric structures. Strong least-squares correlations occur involving the electron population parameters of all atoms for certain of the multipole terms, namely those odd-order terms that are invariant under the symmetry operations of the space group. PMID- 8217025 TI - Aging and human hormonal and pressor responsiveness to angiotensin II infusion with simultaneous measurement of exogenous and endogenous angiotensin II. AB - A decline in the function of the renin angiotensin aldosterone system may induce adaptive changes in response to angiotensin II (ANG II) with age. We have examined platelet ANG II receptor density, blood pressure and aldosterone responses to ANG II [Asn1, Val5-ANG II] (Hypertensin, Ciba Geigy, Horsham, Sussex, England) infusion in 8 young, 24 to 30 years, and 8 older, 54 to 65 years, healthy volunteers. To measure circulating ANG II, we established a new method for specific and simultaneous measurement of exogenous [Asn1, Val5] (Hypertensin) and endogenous [Asp1,Ile5] ANG II in plasma by using isocratic HPLC and radioimmunoassays with cross-reacting antibodies and compared results with immunoreactive ANG II which was measured conventionally using monoclonal antibodies. Baseline endogenous ANG II (Asp1,Ile5-ANG II) levels in venous plasma were marginally, but not significantly, lower in the old [mean (95% confidence limits): 3.4 (< 0.1 to 7.7) v 3.7 (1.2 to 6.2), fmol/mL] and during suppression by the Hypertensin infusion appeared consistently, but not significantly, lower in the old [0.9 (0 to 3.1) v 2.1 (0.6 to 3.7), after 3 ng/kg/min], while the same infusion rate in young and old resulted in similar plasma Hypertensin levels. Baseline systolic blood pressure (SBP) was similar in both groups but the percentage increases in SBP at infusion rates of 1, 3.0, and 10 ng/kg/min were greater in the old than in the young (9.1 v 2.8, P < .05; 16.3 v 8.0, P < .01; 30.4 v 14.0%, P < .001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217026 TI - Response of ambulatory blood pressure to antihypertensive therapy guided by clinic pressure. AB - The objective of this prospective study was to define the limits below which ambulatory blood pressure (BP) does not decrease in patients with essential hypertension, when the decision to institute and intensify drug treatment is based on conventional blood pressure measurements. After a 1 month placebo run-in period, 30 patients were treated for 1 year with the converting enzyme inhibitor lisinopril or the calcium antagonist isradipine; dose adjustments and the decision to add hydrochlorothiazide were based on conventional blood pressure measurements in the clinic. Ambulatory blood pressure was recorded during 24 h in the run-in period and after 16, 24, and 52 weeks of active therapy. The baseline ambulatory blood pressure below which pressure does, on average, not decrease during active treatment was defined as the pressure at which the regression line between the on-treatment pressure and blood pressure in the run-in period intersects the line of identity. The systolic/diastolic blood pressure limits were similar for the three assessments during active treatment and averaged 128/88 mm Hg for daytime, 106/73 mm Hg for nighttime pressure, and 119/81 mm Hg for the whole 24 h, with upper 95% confidence limits of 137/93, 115/78, and 127/86 mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217027 TI - Ambulatory blood pressure changes in the menstrual cycle of hypertensive women. Significance of plasma renin activity values. AB - Blood pressure (BP) changes during the menstrual cycle (MC) have not been studied in hypertensive women in relationship to changes in sex hormone levels and plasma renin activity (PRA). We therefore carried out 24 h ambulatory BP recordings and hormonal measurements in 34 hypertensive and 27 matched normotensive women during the follicular ovulatory and luteal phases of the menstrual cycle. Plasma renin activity was similar in the two groups and rose significantly during the luteal phase only in the hypertensives (P < .01). There were no differences in plasma estradiol or progesterone between the normotensives and hypertensives, but testosterone was higher in the hypertensives during the ovulatory (P < .01) and luteal (P < .001) phases. Blood pressure did not change in the normotensives throughout the cycle, but it increased in the hypertensives during ovulation (P < .01). When patients were divided according to mean menstrual cycle PRA, only those with relatively low PRA (< 2 ng/mL/h) had a significant BP rise during ovulation and it primarily occurred at night (P < .05). The results demonstrate that premenopausal hypertensive women have increased testosterone during ovulation and increased testosterone and PRA during the luteal phase of the cycle. Like normotensives, hypertensives with relatively high PRA exhibit no change in BP during the cycle, whereas those with relatively low PRA have a nighttime increase in BP during ovulation. PMID- 8217028 TI - Effect of cytokines on cytosolic-free calcium in human platelets from essential hypertensives. AB - The different effects of cytokines on cytosolic-free calcium concentration ([Ca2+]i) and intracellular stored calcium were investigated in platelets from 35 essential hypertensive patients (HT) and 45 age- and sex-matched normotensive control subjects (NT). Erythropoietin (EPO) and interleukin 2 significantly increased platelet [Ca2+]i, whereas platelet-derived growth factor, and fibroblast growth factor had no significant effect on [Ca2+]i. The EPO-induced rise of [Ca2+]i was significantly higher in HT compared to NT (15.2 +/- 4.3 nmol/L v 1.3 +/- 1.7 nmol/L, P < .01). Preincubation with EPO significantly increased calcium in intracellular stores in platelets from HT and NT. Inhibition of protein kinase C significantly enhanced EPO-induced rise of stored calcium. It is concluded that an increased response of HT to EPO may be associated with essential hypertension. PMID- 8217029 TI - Effect of phosphoramidon (endothelin converting enzyme inhibitor) and BQ-123 (endothelin receptor subtype A antagonist) on blood pressure in hypertensive rats. AB - We reported previously that the endothelin converting enzyme (ECE) inhibitor phosphoramidon lowers mean arterial pressure (MAP) when infused in conscious, spontaneously hypertensive rats (SHRs). In this study we determined the dose response relationship for this action in SHRs and in a high-renin hypertensive model, the renal artery-ligated rat. We also determined whether the ETA receptor antagonist BQ-123 (cyclo [D-Trp-D-Asp-Pro-D-Val-Leu]) might lower MAP in hypertensive rats. Phosphoramidon lowered MAP by 9 +/- 4, 31 +/- 4, and 40 +/- 4 mm Hg after 5 h when infused in SHRs at 10, 20, and 40 mg/kg/h. This lowering of MAP was associated with dose-related inhibition of the pressor response to a bolus intravenous injection of big ET (1-39) at 1 nmol/kg. BQ-123 also lowered MAP in SHRs (by 25 +/- 3 mm Hg), but only at a very high dose (50 mg/kg/h for 5 h). At this dose, BQ-123 blocked the pressor response to a bolus intravenous injection of ET-1 (1 nmol/kg), but the blockade was incomplete. Phosphoramidon infused in conscious, renal hypertensive rats lowered MAP by 31 +/- 9, 46 +/- 8, and 54 +/- 1 mm Hg after 5 h at 10, 20, and 40 mg/kg/h, respectively. This lowering of MAP was associated with blockade of the pressor response to big ET (1 39). BQ-123 did not lower MAP in renal hypertensive rats when infused at 30 mg/kg/h for 5 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217030 TI - Opposite effects of cell growth factors and cicletanine sulfate on the sodium independent [Cl-/HCO3-] exchange in cultured vascular smooth muscle. AB - Cicletanine sulfate was tested on bicarbonate-dependent pHi changes in cultured vascular smooth muscle (A10 line). Cicletanine sulfate exhibited double reactivity with regard to the cell alkalinization induced by bicarbonate uptake. The analysis of 11 concentration-response curves revealed a high reactivity component (IC50 approximately 3.5 x 10(-8) mol/L) and a weak reactivity component (IC50 approximately 4 x 10(-4) ml/L). Regarding the cell acidification induced by bicarbonate extrusion, cicletanine sulfate exhibited a single high reactivity component (IC50 = 5.9 +/- 2.9 x 10(-7) mol/l; mean +/- SD, n = 7). The high and weak reactivity sites were both sensitive to DIDS. Analysis of the data strongly suggested that the highly reactive site corresponds to a sodium-independent (Cl /HCO3-] exchanger, which catalyzes net bicarbonate efflux, and the weak reactivity site corresponds to the inwardly directed sodium-dependent [Cl-/HCO3-] exchanger. Three cell growth factors--epidermal growth factor, arginine vasopressin, and insulin--were able to stimulate the sodium-independent [Cl-/HCO3 ] exchanger in A10 cells. Finally, cicletanine sulfate (30 mumol/L) partially inhibited serum-dependent A10 cell growth. In conclusion, cicletanine sulfate and cell growth factors exert opposite effects (inhibition and stimulation, respectively) on the sodium-independent [Cl-/HCO3-] exchanger in cultured vascular smooth muscle. The effect of cicletanine sulfate on the sodium independent [Cl-/HCO3-] exchanger may account for the ability of cicletanine to favorably alter vascular pathology in spontaneously hypertensive rat (SHR) models. PMID- 8217031 TI - Predominance of high molecular weight plasma Na(+)-K(+)-ATPase inhibitor in essential hypertension. AB - Circulating inhibitors of the transport enzyme, sodium-potassium-activated adenosine triphosphatase (Na(+)-K(+)-ATPase), have been shown to be of possible pathogenetic importance in the mechanism of essential hypertension. Although previous studies have demonstrated the presence of both high molecular weight (HMW) and low molecular weight (LMW) natriuretic plasma Na(+)-K(+)-ATPase inhibitors, no previous attempts have been made to ascertain whether HMW or LMW forms predominate in hypertension. In this study, plasma samples obtained from 26 patients with essential hypertension, 12 normotensive controls, and six normotensives with a family history of hypertension, were separated into HMW and LMW moieties by passage through a 1 kDa Amicon membrane. The LMW moiety was separated on C18 Sep-Pak cartridges, applying a 10% step-wise acetonitrile trifluoroacetic acid gradient. The HMW moiety was further separated on Sephadex G 75. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that the fraction with inhibitory activity contained a distinct 12 kDa protein band, with staining intensity depending on the presence or absence of hypertension. Na(+) K(+)-ATPase inhibitory activity was found in several LMW fractions, but differences between hypertensives and normotensives were observed in only one fraction (0.29 +/- 0.12 SD v 0.11 +/- .12 mumol/L ouabain equivalents, P < .01). Na(+)-K(+)-ATPase inhibitory activity in the HMW fraction was 38 x the inhibitory activity in the LMW fraction and was significantly increased in hypertensives as compared to normotensive controls (10.9 +/- 8.9 v 1.3 +/- 0.8 mumol/L ouabain equivalents, P < .01). Inhibitory activity in both HMW and LMW fractions correlated positively with mean blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217032 TI - Effect and tolerability of combining lovastatin with nifedipine or lisinopril. AB - Single cardiovascular risk factor intervention is probably not sufficient to prevent atherosclerosis progression. There is a lack of data on concomitant use of hypocholesterolemic agents and antihypertensive drugs with respect to possible interactions and adverse experiences. We studied 293 patients (below 65 years of age) under treatment with either lisinopril (n = 144) or nifedipine (n = 149) for mild to moderate hypertension for 10 weeks, and with serum cholesterol above 6.5 mmol/L, who were randomized to either lovastatin 20 mg every day or placebo in a double-blind, double-dummy design for 6 weeks. Lovastatin effectively lowered cholesterol by 16% and 15% in the lisinopril and nifedipine group respectively (P < .01 compared to placebo for both groups) without any negative impact on the antihypertensive efficacy of either lisinopril or nifedipine. The drugs in combination were well tolerated and did not affect the well-being of the patients, and did not cause any more adverse effects than the antihypertensive agents alone. Liver enzymes increased slightly during lovastatin therapy, while no case of myopathy was reported. Combined therapy with lovastatin and antihypertensive therapy can be safely undertaken. PMID- 8217033 TI - Mechanisms of ozolinone-induced renin release and diuresis. AB - Dextrorotatory (+) and levorotatory (-) ozolinone (ozo) were injected directly into the left renal artery of volume-expanded anesthetized dogs. (+)Ozo (40 micrograms/kg/min) had no effect on urine flow and fractional excretion of Na+, Cl-, or K+ when compared with the basal period. Comparison of (-)ozo to (+)ozo revealed the following: urine flow 4.0 +/- 0.3 v 0.9 +/- 0.1 mL/min (P < .001); FENa+ 29.8 +/- 3.0 v 5.6 +/- 0.3% (P < .001); FECl- 35.7 +/- 4.1 v 5.8 +/- 0.4% (P < .001); FEK+ 87 +/- 4 v 49 +/- 5% (P < .001). Glomerular filtration rate (GFR) and renal plasma flow (RPF) did not change. The renin secretory rate (RSR) was significantly higher with (-)ozo than with (+)ozo (498 +/- 113 v 210 +/- 53 ng A I/mL/hr.mL/min). Moreover, (-)ozo significantly increased urine PG excretion compared to basal values: 466 +/- 63 v 263 +/- 30 pg/min (P < .05). Indomethacin (2 mg/kg) markedly blunted the effects of (-)ozo on PG and RSR, and completely abolished the rise in PRA. (+)Ozo had no significant effect on urine PG excretion. Neither (-)ozo nor (+)ozo had an effect on renin production in isolated glomeruli. By contrast, (-)ozo but not (+)ozo increased PGE2 synthesis in papillary and medullary slices. The data are consistent with the proposal that the effect of (-)ozo on renin secretion and PRA is through a PG-dependent mechanism, and that it requires an intact macula densa mechanism. PMID- 8217034 TI - Determinants of left ventricular function before and after regression of myocardial hypertrophy in hypertension. AB - Using digitized M-mode echocardiograms, we evaluated the determinants of left ventricular (LV) systolic and diastolic function in 30 hypertensives with LV hypertrophy (LV mass > 230 g and normal LV diastolic diameter), before (LV mass 319 +/- 26 g) and after normalization of LV mass (196 +/- 21 g) by antihypertensive treatment with angiotensin converting enzyme inhibitors. As a control group we selected 50 normal subjects. Using multiple regression analysis we studied the relative role of preload (LV end-diastolic diameter), afterload (end-systolic wall stress), inotropic state (systolic pressure/end-systolic LV diameter ratio), and LV mass on LV systolic (peak shortening rate of LV diameter) and diastolic function (peak lengthening rate of LV diameter). The major determinant of systolic function was the end-systolic stress in hypertensives before treatment and the systolic pressure/end-systolic LV diameter ratio in normals and in hypertensives after treatment. The major determinant of diastolic function was LV mass in hypertensives before treatment and end-systolic stress in normals and in hypertensives after normalization of LV mass by treatment. Preload seems not to influence LV function in normals and in hypertensives with normal LV diameter. The inotropic state is the major determinant of systolic function in normals and in hypertensives after treatment, whereas this role is played by afterload in hypertensives before treatment. The diastolic function is primarily influenced by after-load in normals and in hypertensives after regression of myocardial hypertrophy, whereas in hypertensives with myocardial hypertrophy LV mass is the major determinant of diastolic function. PMID- 8217035 TI - Borderline hypertension. A 24-hour abnormality. AB - It has recently been questioned whether borderline hypertension (BH) is a reality or just an artefact due to the person's knowledge of his or her raised blood pressure. This issue was evaluated by measuring ambulatory blood pressure (ABP) in subjects with BH, compared to normotensive individuals (NC). In particular, we wanted to investigate whether the basal blood pressure levels during sleep at night were elevated in BH subjects, or whether these individuals would normalize blood pressure during periods of low psychological arousal. Twenty-four-hour ABP was measured using the Spacelabs monitor 90202. Forty-nine BH subjects (systolic blood pressure [SBP] 140 to 160 mm Hg or diastolic blood pressure [DBP] 85 to 95 mm Hg) and 18 NC (SBP 110 to 130 mm Hg and DBP 60 to 80 mm Hg) were recruited from an unbiased population sample (age 20 to 28 years). The classification of BH and NC, respectively, was confirmed by intraarterial BP recordings. There was the expected variation of blood pressure throughout the 24 h (the highest values in the afternoon and lowest at night). SBP was significantly higher in the BH than in the NC group for the entire 24 h as well as during the four 6-h periods (morning P = .007, afternoon P < .001, evening P < .001, and night P = .025). A smaller but significant difference between the groups was seen for DBP but only in the afternoon and in the evening (morning P = .167, afternoon P = .022, evening P = .038, night P = .310).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217036 TI - Chronic ethanol treatment increases the circulating plasma levels of B-type natriuretic peptide (BNP-45) in the rat. AB - Chronic ethanol ingestion is associated with a number of cardiovascular disorders, including stroke, heart failure, and hypertension. Given that the regulation of A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) is known to be altered in both congestive heart failure and essential hypertension, we have investigated the regulation of BNP under the influence of ethanol ingestion. Sprague-Dawley rats were given ethanol in drinking fluid for a 6-week period, while a weight-matched liquid-restricted group received an equivalent volume of ethanol-free solution. Plasma BNP levels were increased in ethanol-treated animals relative to both liquid-restricted and normal control groups. No changes in cardiac BNP gene expression were observed, but an increased trend in atrial tissue BNP levels was evident. No changes in either the mRNA, tissue, or plasma levels of ANP were evident. These results suggest a differential regulation of natriuretic peptides under the influence of ethanol, and implicate chronic ethanol ingestion as a further clinical condition under which the plasma levels of a natriuretic peptide may be elevated. PMID- 8217037 TI - Disseminated intravascular coagulation: clinical complexities of aberrant coagulation. AB - When the critically ill patient's clinical course is complicated by disseminated intravascular coagulation (DIC), significant physiologic disequilibrium and life threatening multisystem events ensue. DIC occurs when an underlying pathologic condition triggers overstimulation of the normal coagulation mechanism resulting in a perplexing clinical picture of disseminated coagulation and excessive fibrinolysis. This article presents a review of normal coagulation physiology and the alterations producing the physiology derangements in DIC. Diagnostic and clinical assessment parameters and therapeutic management goals for the critically ill DIC patient also are included. The critical care nurse's role in knowledgeable assessment, rapid intervention, and ongoing evaluation of the patient's therapeutic responses are essential to maximize positive outcomes for the DIC patient. PMID- 8217038 TI - Mediators of coagulation and inflammation: relationship and clinical significance. AB - Inflammation and coagulopathies are currently thought to play a role in the pathogenesis and pathophysiology of many forms of critical illness, particularly sepsis, multiple organ dysfunction, DIC, and reperfusion injury. Because much of the new pharmacologic research and therapy focuses on inflammation and coagulation mechanisms, it is imperative for the critical care nurse to have a basic understanding of these two complex mechanisms to intelligently and safely administer these drugs and to increase his or her understanding of the disease process and its manifestations. This article will provide an overview of the significant features of inflammation and coagulation and their close relationship. Major clinical syndromes affecting the critical care population will then be described relative to these inflammatory and coagulation events. PMID- 8217039 TI - Arterial thrombosis: putative role of lipoprotein(a). AB - Lipoprotein(a) has been associated with several arterial thrombotic disorders. This article presents evolving concepts of Lp(a) and its potential role in coagulation. An overview of lipoprotein structure and function provides background information for further understanding of the pathophysiologic role of Lp(a) in atherosclerosis and thrombosis. Further research is needed to clarify the function of Lp(a) in humans and its role in arterial thrombosis. PMID- 8217040 TI - Congenital coagulopathies in the pediatric population. AB - Congenital coagulopathies in the pediatric population continue to be a serious cause of morbidity and mortality. Familiarity with such disorders is essential for individuals responsible for the care of children. This article discusses a variety of congenital and inherited coagulation disorders, classifying them in either the vascular, platelet, or plasma phase. PMID- 8217041 TI - Acquired coagulopathies. AB - Unexpected hemorrhage related to acquired coagulopathies is a serious threat to many critically ill patients. The critical care nurse must possess a thorough knowledge of the basic coagulation process and the pathophysiology of common acquired coagulopathies. This article reviews the coagulation process and the conditions associated with acquired coagulopathies including vitamin K deficiency, liver disease, and renal disease. Also reviewed are common factors that contribute to the development of acquired coagulopathies, such as total parenteral nutrition (TPN) and antibiotics. PMID- 8217042 TI - Postoperative coagulopathies. AB - Because complications associated with postoperative coagulopathies are significant, prevention, early evaluation, and appropriate management are essential. The etiologies of postoperative coagulopathies are multifactorial and can be evaluated by a systematic clinical approach. Treatment should not be arbitrary but directed at specific defects. This article reviews the normal hemostatic mechanisms and presents the etiologies and current management strategies for common postoperative coagulopathies. PMID- 8217043 TI - HELLP syndrome and coagulopathies of pregnancy. AB - The critically ill obstetric patient presents many unique management problems to the health care provider. Both the mother and her fetus can be profoundly affected by disease processes. One such challenging management problem in the obstetric population is the development of an underlying coagulopathy. Coagulopathies during pregnancy present diverse clinical pictures. The coagulopathy may be unaffected by the pregnancy or there may be a dynamic relationship between the pregnancy and the pathologic state. With the well-being of the mother and her fetus dependent upon management decisions, each must be considered in the management plan. PMID- 8217044 TI - Thromboembolic phenomena. AB - Venous thrombosis and thromboembolic phenomenon affect over 2 million people each year. Estimates indicate that there are 50,000 deaths from pulmonary embolus annually and that this number has not declined in 20 years. Understanding the etiology and prevention of this complication is essential to the critical care health care practitioner. PMID- 8217045 TI - Venous thrombosis: antithrombin III deficiency. AB - Antithrombin (ATIII) is believed to be one of the body's most powerful natural anticoagulants, so individuals with a deficiency of this protein exhibit a marked propensity to venous thrombosis. This article will focus on the pathophysiology of this disorder, including clinical presentation, diagnosis, and treatment. PMID- 8217046 TI - Bleeding complications in the patient with cardiac disease following thrombolytic and anticoagulant therapies. AB - Thrombolytic and anticoagulant therapies are used frequently in the cardiac patient. Bleeding complications and other coagulation defects, such as heparin induced thrombocytopenia (HITP), can occur following the administration of these drugs. Nurses caring for the cardiac patient need to be aware of the potential for bleeding and know how to safely and effectively care for the patient who experiences a bleeding event. PMID- 8217047 TI - Use of heparinoids to treat acute ischemic stroke. AB - Low molecular weight heparinoids (LMWHs) offer a new treatment option to patients experiencing acute ischemic stroke. These heparin sub-fractions provide an increased risk/benefit ratio when compared to standard heparin, and allow patients to achieve better functional outcomes with fewer neurologic deficits. Because LMWHs separate the antithrombotic activity of standard heparin from its anticoagulant and antiplatelet-aggregating effects, they are safer, but equally or more effective than heparin. PMID- 8217048 TI - Bone marrow transplantation: critical care implications. AB - Bone marrow transplantation is an effective treatment for a growing list of disease processes both malignant and non-malignant. Complications associated with marrow transplantation may be related to ablative therapy, immunosuppression, graft-versus-host disease, and recurrence of the underlying disease. Survival depends upon prompt recognition of problems and timely institution of specific interventions, both medical and nursing. Nurses caring for bone marrow transplant recipients face a never-ending and ever-changing challenge to stay on top of the day-to-day problems and patient care crises that can occur. PMID- 8217049 TI - Blood component replacement therapy. AB - Blood component replacement therapy is required frequently for critically ill patients. Critical care nurses have a major role in monitoring patients for transfusion reactions and response to therapy. A fundamental understanding of blood components, as well as indications for and complications and hazards of component therapy, is essential for accurate assessment of the patient and evaluation of response to therapy. PMID- 8217050 TI - Arterial catheter complications and management problems: observations from AACN's Thunder Project. AB - Arterial cannulation, while common in critical care, is a procedure with attendant risks of complications. Anecdotal data from the American Association of Critical Care Nurses' Thunder Project provided evidence that catheters, insertion sites, and monitoring systems continue to be sources of complications. The problems have not changed since arterial cannulation began. Line management issues cannot be resolved until low-maintenance systems are developed. PMID- 8217052 TI - Hippocampal benzodiazepine receptors in schizophrenia. AB - Benzodiazepine receptor sites were determined by saturable [3H]flunitrazepam binding in hippocampal tissue from schizophrenic and control subjects. No difference in receptor density or affinity between the two groups was observed, indicating that the previously identified GABAergic deficit in the hippocampus in schizophrenia does not apparently lead to up-regulation of these receptor sites. The implications of this finding are discussed. PMID- 8217051 TI - Opioid and GABA modulation of accumbens-evoked ventral pallidal activity. AB - The principle output of the nucleus accumbens innervates the ventral pallidum and rostral substantia innominata. GABA and opioid peptides are among the neurotransmitter candidates for this projection. The goal of the present experiments was to delineate further the physiology and pharmacology of the accumbens projection to the ventral pallidum. The trans-synaptic responsiveness of ventral pallidal and rostral substantia innominata neurons to electrical stimulation of the nucleus accumbens was examined concurrently with the ability of microiontophoretically applied morphine (an opioid agonist), naloxone (an opioid antagonist) and bicuculline (a GABA antagonist) to modulate evoked responses. Accumbens stimulation altered the firing rate in 60% of the 132 neurons tested. Fifty-two percent of responding neurons exhibited simple excitations or inhibitions in response to accumbens stimulation, while 48% exhibited complex response sequences with two or more evoked components. Predominant responses consisted of a short latency (< 10 ms) and short duration (10 ms) excitation (51% of responding neurons) and an inhibition with a variable, onset latency and, duration (52% of responding neurons). Evoked responses often occurred within limited areas within the ventral pallidum suggesting that activation of descending afferents can influence discrete targets within the region. A large majority (> 80%) of neurons evoked by accumbens stimulation also exhibited a current-dependent and naloxone-sensitive increase in spontaneous firing to microiontophoretically applied morphine. Morphine shortened the duration of the accumbens-evoked, short latency excitation and attenuated the magnitude of the long-latency inhibition. Evoked responses in the presence of morphine were opposite to those observed with naloxone, but similar to bicuculline. Thus, opioid receptor activation may be functionally antagonistic to GABAergic neurotransmission in the ventral pallidum. The prominence of accumbens evoked and morphine-sensitive neurons within the ventral pallidum corroborates the density of accumbens and opioid input to this brain region, and demonstrates that opioids serve as an important influence on neuronal activity and information processing in the ventral-striatopallidal pathway. PMID- 8217053 TI - Influence of aminophylline and 8-(p-sulfophenyl)theophylline on the anticonvulsive action of diphenylhydantoin, phenobarbital, and valproate against maximal electroshock-induced convulsions in mice. AB - Aminophylline (theophylline2.ethylenediamine) in the dose of 12.5 mg/kg (i.p.) was ineffective upon all antiepileptic drugs studied and at the higher dose of 25 mg/kg, impaired the anticonvulsant action of phenobarbital and valproate against maximal electroshock in mice. The protection offered by diphenylhydantoin was diminished by aminophylline at 50 mg/kg (0.238 mmol of anhydrous theophylline/kg). In contrast, 8-(p-sulfophenyl)theophylline (a theophylline derivative unable to cross the blood-brain barrier) in the dose of 80 mg/kg (0.238 mmol/kg) did not influence the protective activity of diphenylhydantoin, phenobarbital, and valproate. It might be concluded that the aminophylline induced impairment of the anticonvulsant action of common antiepileptic drugs results from the central effects of this methylxanthine. PMID- 8217054 TI - Action of pineal indoleamines on the reproductive systems of the male C57 mouse and golden hamster. AB - Intraperitoneal administration of melatonin, methoxytryptamine and methoxytryptophol in the late afternoon to mice exposed to a 14L:10D photoperiod induced appearance of necrotic cells in seminiferious tubules and an increase in incidence of aspermic tubules. The histological appearances of the seminal vesicles and coagulating glands were, however, unaffected by the treatments. Treatment of mice with methoxyindoleacetic acid did not produce discernible changes in the testes and accessory sex organs. Subcutaneous injections of the aforementioned pineal indoles at a dose of 250 micrograms/injection for 3 months to mature male hamsters kept under a 14L:10D photoperiod did not evoke changes in the testes, seminal vesicles and coagulating glands, suggesting a down-regulation of melatonin receptors by administration of a high dose of pineal indole over a prolonged period. PMID- 8217055 TI - Suppression of domoic acid induced seizures by 8-(OH)-DPAT. AB - Microinjections of the neuroexcitotoxin, domoic acid (DOM), in the ipsilateral rat hippocampal CA-3 region, induced generalized electrical seizure discharge activity, characterized by spikes and waves, followed by intermittent burst discharges. Computerized EEG analysis exhibited relative dominance of delta and theta and reductions in alpha and beta activities during domoic acid epileptogenesis. Seizure discharge activity was attenuated by the microinjection of the 5-HT1A agonist, 8-hydroxy-2-(di-N-propylamino)tetralin(8-(OH)-DPAT) and augmented by the specific 5-HT1A antagonist, spiroxatrine in the contralateral hippocampal CA-3 region. Neuronal recovery following 8-(OH)-DPAT was associated with significant reductions in the relative dominance of delta and theta and increases in the alpha and beta activities. The results suggest that activation of serotonergic 5-HT1A receptor in the hippocampus has a neuroprotective action. PMID- 8217056 TI - Sodium-dependent release of exogenous glycine from preloaded rat hippocampal synaptosomes. AB - The effect of high potassium, veratridine, and ouabain stimulation upon the release of exogenously-loaded [3H]glycine was evaluated in crude synaptosomal preparations from rat hippocampi by means of a superfusion technique in the presence of media with different ionic compositions and of tetrodotoxin (TTX). Four minute superfusion of synaptosomes with 30 mM KCl, 10 microM veratridine or 0.4 mM ouabain caused a significant increase in the [3H]glycine efflux which averaged 6.6 +/- 0.2, 25.5 +/- 1.0, and 8.9 +/- 1.0% of the total radioactivity present in the synaptosomes, respectively. The omission of Ca2+ ions in the superfusion medium markedly decreased K(+)-evoked [3H]glycine efflux (2.5 +/- 0.5%), did not appreciably modify that evoked by veratridine (24.2 +/- 2.0%) and significantly increased that evoked by ouabain (18.5 +/- 0.5%). The superfusion of synaptosomes with Na(+)-free media always resulted in a drastic decrease of the depolarization-stimulated [3H]glycine efflux, whereas the omission of Cl- generally resulted in a moderate increase of [3H]glycine efflux. TTX (0.8 microM) markedly affected the stimulatory effect of veratridine (2.5 +/- 0.9%) and ouabain (2.2 +/- 0.5%), but failed to modify significantly that evoked by high potassium (6.5 +/- 0.7%). Finally, [3H]glycine was seen readily to exchange in a partially sodium-dependent way with unlabelled glycine present in the medium. On the whole these findings appear to be consistent with the neurotransmitter character of the glycine release from hippocampal synaptosomes. PMID- 8217057 TI - Effect of diazepam on muscle weakness in a model of myasthenia gravis in rats. AB - Rats chronically received alpha-bungarotoxin which caused a reduction of nicotinic acetylcholine receptors and weakness, especially of lip muscles. It was found that diazepam (0.75-2 mg kg-1, s.c.), after a 15 min period of excitation and increased lip weakness, caused sedation and some improvement of the lip. Even after 5 mg kg-1 diazepam, muscle function was not markedly affected and breathing appeared normal. It is concluded that sedation in rats by diazepam does not entail aggravation of the muscle weakness caused by a partial neuromuscular block. PMID- 8217058 TI - Dopamine D2 blocking activity and plasma concentrations of remoxipride and its main metabolites in the rat. AB - Remoxipride and its active metabolites, the phenolic compounds FLA797(-) and FLA908(-) and the catecholic NCQ436(-) and haloperidol, were examined for their ability to block hypothermia in the rat induced by dopamine (DA) D2 receptor stimulation. In addition, plasma levels of remoxipride and its active metabolites were measured using HPLC methods. Remoxipride (1 mumol/kg), given 30 or 15 min prior to, or 5 and 15 min after, the DA agonists, blocked the hypothermia induced by the DA D2 receptor agonists quinpirole (0.25 mg/kg s.c.) and pergolide (0.1 mg/kg s.c.). Administration of remoxipride by the i.v. or s.c. routes was more effective than by the i.p. route. FLA797(-), FLA908(-), and haloperidol were more effective than remoxipride in preventing the hypothermia caused by quinpirole, while NCQ436(-) was less effective than remoxipride. The variation in time of remoxipride's action and effectiveness in blocking the induced hypothermia followed the variations in plasma concentrations. The plasma concentrations of the active metabolites were below the limit of determination (< 2 nmol/l). Based on estimation of free brain concentrations at effective dose levels together with in vitro affinities for the DA D2 receptor it was concluded that the metabolites FLA797(-), FLA908(-), and NCQ436(-) do not appear to contribute to the antagonism of DA D2 mediated neurotransmission following a low remoxipride dose (1 mumol/kg). PMID- 8217059 TI - [Diagnosis of chronic alcohol abuse in intoxicated drivers: carbohydrate deficient transferrin (CDT) in combination with other parameters]. AB - In 109 drunken male drivers from the area of Rostock the marker of alcohol abuse CDT was superior to the established laboratory parametres gammaglutamyltransferase (GGT) and mean cell volume (MCV) concerning the diagnostic efficiency. The prerequisite for the high diagnostic evidence of the CDT is the quantification of the minor band and the definition of standards of valuation by comparative studies with defined groups of probands (alcoholics, normal population). The combination of the 3 parametres CDT/GGT/MCV gave in 67% of the examined drunken drivers more or less strong hints at chronic alcohol abuse. The BAC of 1.6/1000 as a base for the decision to cause a medical psychological examination (in case of "poison-resistance") turned out in this study to be an interchangeable, incomprehensible value. In about two thirds of the examined drunken drivers laboratory findings were pathological also in case of BAC below 1.6/1000. According to the experiences existing so far the parametres-combination CDT/GGT is unreservedly suitable as a screening procedure for the registration of potential or manifest alcoholics. Because the examinations may be performed from the usual blood samples for the BAC-detection these laboratory parametres really offer themselves for questions of traffic medicine. Further investigations are necessary. PMID- 8217060 TI - [Alcohol intoxication at the wheel in the Waadt canton (Switzerland).A comparative study of penal and administrative measures 1970 and 1989 in the canton capital city (Lausanne) and a rural area]. AB - The canton of Vaud is one of the major wine-growing areas of Switzerland. The driving ban rate for drunk driving is the highest in the country. This is the result of the very important rise in the number of drivers intercepted by the police for drunk driving (accidentless cases), in the course of the last ten years (+260%). In order to find out what penal and administrative measures were taken against drunk drivers (those who did not commit an accident), a comparative retrospective study of the offenses committed in the area of Lausanne and in rural area of the canton of Vaud (La Broye) was undertaken. This study deals with the years of 1970 and 1989. In a parallel, the average blood alcohol concentration (BAC) value, relative distribution of the BAC (frequency profile), and the concordance between the doctor's medical examination and the suspect's BAC were studied. Our results demonstrate that only the urban area (Lausanne) showed a significant increase in the drunk-driving offenses without accident, resulting in a significant decrease in the average BAC value as well as a veering towards the left of the BAC frequency profile curve. The legal sanctions and the administrative measures diverge according to the different areas, the most striking fact is the lowering of the average term of imprisonment for second-time or multiple offenders in the study group of Lausanne. The results of the clinical examination undertaken by the doctor at the moment of the blood test have shown that there is often a difference between the clinical evaluation and the actual BAC: for a BAC of 2 to 3/1000, the objective clinical symptoms of drunkenness (Romberg, unstable gait, coordination troubles) are noticed in only half of the cases. As a result, the assessment is no longer based on objective criteria but on subjective criteria as well as on the life-style of a certain period. In conclusion it is our belief that the efforts made by the vaudois police (especially in urban areas) should be pursued further, since positive results are apparent. The Judiciary system should however rebalance the sanctions delivered to drunk-drivers, showing greater severity towards second-time or multiple offenders. PMID- 8217061 TI - [Breathalizers in practical use by the Hamburg police]. AB - The pretest, which measures the alcohol content in one's breath, will remain necessary within the field of police work regardless as to whether this process will be recognized in the future as a means of reaffirming existing evidence. Inaccurate measurements, especially those which are lower than should be in the area of 0.08% and 0.11%, lead to inaccurate rulings, which in turn, directly influence traffic safety. After examining 682 breathalizer measurements, the Hamburg police department released the following information: even after having replaced the older Drager AT 7310 with the newer AT 7410 breathalizer, larger discrepencies than those that had appeared in earlier examinations still occurred. There are too many inaccurate measurements which, in actuality, are overwhelmingly a result of the conditions surrounding police use of breathalizers. More detailed instructions describing proper application of these devices are, at present, more suitable for increasing the accuracy of the breathalizer measurements than the technical improvement of the instruments would be. PMID- 8217062 TI - The challenge of predicting response to stabilising lithium treatment. The importance of patient selection. AB - Lithium treatment, an approach with well documented efficacy, has recently been losing its treatment value. Lithium continues working, however, for those patients for whom it was proven efficacious; that is, most patients with primary episodic affective disorders. Such responders to lithium prophylaxis can be reliably identified beforehand by a comprehensive clinical assessment. The explanation for the paradox of lithium's lost efficacy lies mostly in the educational bias against a comprehensive patient assessment, and in the shift in diagnostic fashion favouring affective disorders and the treatment methods associated with them in the clinicians' minds. PMID- 8217063 TI - Who responds to prophylactic lithium therapy? AB - The search for predictors of outcome has not been particularly rewarding, and the use of lithium remains empirical: a trial of lithium is the most powerful predictor of outcome. However, lithium is a highly specific treatment for bipolar disorder. In non-bipolar affective disorder, factors of interest are correlates of bipolar disorder: mood-congruent psychotic features, retarded-endogenous profile, cyclothymic personality, positive family history of bipolar illness, periodicity, and normality between episodes of illness. PMID- 8217064 TI - Length of lithium treatment needed to eliminate the high mortality of affective disorders. AB - Recent studies have indicated that long-term lithium treatment reduces the expected suicidal activity and overall mortality of patients with affective disorders. Based on the data from the lithium clinics in Berlin and Hamilton (n = 512), a minimum length of two years of continued lithium treatment is needed to reduce the high mortality resulting from affective disorders. PMID- 8217065 TI - Columbia atypical depression. A subgroup of depressives with better response to MAOI than to tricyclic antidepressants or placebo. AB - We summarise a series of studies using a MAOI to help establish the validity of a subgroup of depressives referred to as atypical depressives. Patients with reactive mood meeting DSM-III criteria for depressive illness who had associated atypical features (which include hyperphagia, hypersomnolence, leaden paralysis, and rejection sensitivity) were randomised to imipramine, phenelzine and placebo. Non-responders were crossed over, and in all there were over 400 patient trials. Phenelzine consistently was found to be superior to imipramine. Only in trials which included patients lacking atypical, vegetative symptoms was imipramine found to equal phenelzine. We conclude that the researcher and the clinician should consider the relevance of the atypical depressive syndrome. PMID- 8217066 TI - Predicting therapeutic results with levoprotiline and maprotiline in major depression: the role of the outcome criteria. AB - We describe a double-blind study involving 58 in-patients with major depression (DSM-III). After one week on placebo, the patients were randomly assigned to either levoprotiline or maprotiline treatment for three weeks. In the next three weeks, responders were maintained on the same medication and non-responders were shifted to treatment with the complementary drug. After the initial three weeks' treatment, 31% of levoprotiline patients and 58% of maprotiline patients had responded. Both in the initial three-week period and after shifting non responders to the complementary drug, there were significant differences in favour of maprotiline. The comparison of properties of different outcome criteria in prediction analyses shows that the final score gives the best agreement with global evaluation; using the delta score (final minus baseline) or ratio score (final/baseline) as the outcome criterion may yield paradoxical results. PMID- 8217068 TI - Prediction: nonsense or hope? AB - Psychiatry and psychopharmacology are no longer aiming to make a decisive breakthrough at the end of the century. Rather than seeking explanations, research workers are looking for 'predictions'. Three main types of prediction are emerging: a tautological, a heuristic, and an irrelevant one. Few predictions found in the recent literature can be marked as 'logical' ones. Nevertheless, predictions play two important roles: they generate new hypotheses that can be falsified in properly designed scientific experiments; they also may serve to falsify given hypotheses. The main recent findings on predictions in psychiatry are briefly summarised. PMID- 8217067 TI - Prediction in drug abuse: cocaine interactions with alcohol and buprenorphine. AB - We describe the limitations on studying the interactions of drugs of abuse in humans. Two 'acute' studies were carried out. In the first study, the administration of alcohol/placebo with cocaine showed the possibility of identifying the euphoric effect of the drugs by the EEG power spectra analysis in terms of enhancement of alpha- and beta-wave activity. The results of the second study, in which cocaine and buprenorphine were administered, show the existence of low-dose interactions and the influence of buprenorphine on craving for cocaine. PMID- 8217069 TI - How incoming guidelines on chiral drugs could impact on the international scenery of drug development.IUPAC. AB - In this review incoming guidelines on chiral drugs are examined for their impact on drug development. Problems related to synthesis, enantiomeric resolution, analytics, pharmacokinetics, preclinical and clinical studies are discussed throughout the paper. Problems related to the validation of an enantioselective assay in pharmacokinetics are certainly the most difficult, mainly for chiral drugs active at low or very low plasma concentrations. The compliance with incoming guidelines on chirality will require new approaches and new technologies and will produce an increased cost of the drug development. PMID- 8217070 TI - Manual ELISA assays on tPA and PAI-1 automated on Novapath I.S. preliminary report. AB - Tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) have been pointed out as markers for deep venal thrombosis, acute myocardial infarction and several thrombotic disorders. This paper reports automation on Novapath I.S. analyzer (BioRad, Segrate Milano) of two manual Elisa procedures on microtritation plates for tPA and PAI-1; Tint Elize tPA and Tint Elize PAI-1 respectively (Biopool Atlanta, Georgia--for Italy Menarini diagnostics, Florence). Automation vs manual procedure allows: 1) higher safety for the operator, 2) better linearity of the standard curve, 3) better analytical precision: 6.8% and 5.3% CV on automation vs 19.8% and 15.7% CV for tPA and PAI-1 respectively, 4) simultaneous assays of tPA and PAI-1, which save time up to 10 hours (6 vs 16 hours), 5) a steady interval between every analytical step, particularly between the interchange of substrate and blocking solution. Accuracy of these procedures must of course be further evaluated. PMID- 8217071 TI - Analytical performance of an heterogeneous enzyme immunoassay using the same separation system. AB - A single "one step" solid phase sandwich enzyme immunoassay was developed. The assay employs two monoclonal antibodies with affinity and specificity for different epitopes of the analyte: one is covalently coupled to peroxidase, while the other one is coupled to biotin. The addition of the reagent to an avidin coated strip gave a specific and efficient mean for binding the sandwich complex to the solid phase, via the high affinity interaction between biotin and avidin. The methodology was applied to the determination of hypophysis hormones (LH, FSH, PRL), tumor markers (CEA, AFP, FRT, hCG beta free subunit, alpha subunit and others alpha-P Amylase). Analytical performances concerning the developed kits are described, demonstrating the good reproducibility, sensitivity, accuracy and the wide application field for this new technology. PMID- 8217072 TI - Evaluation of new product for hydroxyproline determination in HPLC. AB - For the determination of hydroxyproline, HPLC methods are specific and sensitive, but expensive and time consuming. The aim of this paper was to evaluate a modification to the HPLC method, which employs a precolumn derivatization by DABSYL chloride. The modified method includes a further derivatization by orthophthalaldehyde (OPA), but it simplifies the chromatographic separation, saving time and reagents. Precision, recovery, linearity and accuracy for both methods have been evaluated. The linear regression analysis of the data has given the following correlation: Y = 1.04 X - 1.08 (r = 0.996). Moreover we checked that the preparation of the mobile phase for the modified method may not be strict. In fact, only two identifiable peaks are present: internal standard amino acid (1st peak) and hydroxyproline amino acid (2nd peak). PMID- 8217073 TI - [Biotechnologic strategy for the study of the pathogenic action of bacteria]. PMID- 8217074 TI - Molecular medicine. The forests, trees, and leaves. PMID- 8217075 TI - Inheriting hearing loss. PMID- 8217076 TI - Ethical dilemmas in molecular genetics. PMID- 8217077 TI - Molecular screening. Prospects for a new approach. AB - Tumors arise through a series of genetic steps that involve alterations of various cellular genes. The recent revolution in molecular genetic techniques has allowed direct identification of genetic changes within tumors. Because these changes are intimately involved in tumor progression, they are specific markers for cancer. A novel assay based on the polymerase chain reaction allows detection of a rare cancer cell containing a specific point mutation among an excess background of normal cells. This technique has allowed identification of p53 gene mutations in pathologic tissue samples from primary head and neck cancer. A small population of cancer cells has been detected in a variety of histologically negative clinical specimens, including saliva, surgical margins, lymph nodes, and chyle. The precise detection of these rare cancer cells in various clinical samples has significant implications for otolaryngology-head and neck surgery. This approach holds promise for screening of head and neck cancer and may call for the reassessment of current histopathologic staging through utilization of new molecular genetic techniques. PMID- 8217078 TI - Somatic gene therapy in otolaryngology-head and neck surgery. AB - The initial clinical trials of somatic gene therapy have demonstrated that gene transfer can be performed safely in a clinical setting and with public acceptance. These trials have focused attention on the broad applications of this technology in routine medical and surgical practice. This article reviews the reasons why somatic gene therapy could lead to significant improvements in clinical practice as well as specific therapies in otolaryngology-head and neck surgery. Early applications include the treatment of inherited diseases such as cystic fibrosis, new approaches for treating malignancies, new methods for enhancing tissue repair, and regeneration after plastic and reconstructive surgery, and the potential for using the thyroid as a target for somatic gene therapy. The following review will illustrate how somatic gene therapy may have a significant impact not only on the treatment of rare genetic diseases but on managing the common problems encountered by physicians and patients in daily practice. PMID- 8217079 TI - The genetics of tobacco-induced malignancy. AB - OBJECTIVE: Several areas of investigation contribute to an increasing understanding of the genetics of malignancies associated with tobacco use. While the strong influence of tobacco exposure on cancer development obscures genetic influences, there are indications that aspects of cancer susceptibility may have a heritable basis. In addition, specific sites within the genome appear to be commonly involved in these malignancies. This review describes research relevant to investigation of the genetics of tobacco-induced malignancy. DATA SOURCES: A review of the pertinent literature covered the past 20 years. References were gleaned from a variety of sources including manual review of the most recent journals, a computerized database (Mini-MEDLINE), references cited in previous works, and our own ongoing research in cancer genetics and molecular biology. STUDY SELECTION AND DATA EXTRACTION: Whenever possible, controlled studies from peer-reviewed journals were used. Where studies have shown conflicting results, the possible confounding factors are discussed. DATA SYNTHESIS: From a broad array of research areas, a view of the genetic aspects of tobacco carcinogenesis emerges. This includes syndromic and nonsyndromic susceptibility, genetic determinants of carcinogen metabolism, DNA adduct formation, and site-specific genetic alterations in tobacco-induced malignancy. In addition to specific gene alterations commonly seen in tobacco-induced malignancy, viral infections may contribute to cancer development through pathways related to tobacco carcinogenesis. CONCLUSION: Further research on many aspects of tobacco-induced carcinogenesis is warranted. Investigation of cancer susceptibility may contribute to understanding DNA surveillance and repair pathways. Carcinogen metabolism investigations have application in cancer detection and prevention schemes. Further understanding of tumor suppressor gene function and the role of gene amplification in carcinogenesis may allow design of gene-specific strategies in cancer treatment. PMID- 8217080 TI - Cloning of tumor suppressor genes involved in solid tumor development. AB - OBJECTIVE: The homozygous inactivation of tumor suppressor genes is a common event in the multistep process of tumorigenesis. The identification of most tumor suppressor genes known to date has come from the study of individuals with a defective copy of such a gene that increases their predisposition to malignancy. Although much is still to be learned about the function of these genes, they all seem to play a role in cell growth regulation. Karyotypic and molecular studies of several solid tumors suggest the presence of at least three tumor suppressor genes on the short arm of human chromosome 3. We present an overview on the progress made in the identification of tumor suppressor genes involved in solid tumor development. CONCLUSION: The explosive effort to map the human genome fueled by the Human Genome Project will facilitate the identification of tumor suppressor genes on chromosome 3 and on other chromosomes within the next 2 to 3 years. This information will not only provide a better understanding in cell cycle regulation and differentiation but also new insights in the design of new therapies for the treatment of human cancer. PMID- 8217081 TI - Cloning genes from an inner ear cDNA library. AB - A rat inner ear complementary DNA (cDNA) library containing 1.9 x 10(6) recombinants was constructed and evaluated. Inserts averaged 2.0 (+/- 2.1) kilobases in length. A subset of inserts was screened for site of expression. Two cDNA transcripts were isolated based on cochlear expression restricted to the spiral ganglion. One transcript showed a high degree of homology to several long interspersed DNA elements, neuron-specific nuclear transcripts thought to be involved in gene regulation. The second transcript showed no homology to known sequences and appears to encode a neuron-specific protein of about 248 amino acids. The library can be used to identify proteins important for inner ear function and disease. PMID- 8217082 TI - Molecular genetic analysis of the mechanism of tumorigenesis in acoustic neuroma. AB - OBJECTIVE: Acoustic neuroma, both familial and sporadic, is clinically and biologically a heterogeneous condition with a wide variation in age of presentation, length of history, and tumor growth rate. In an attempt to correlate this clinical diversity with the underlying molecular pathology, we have analyzed 43 paired blood-tumor DNA samples from patients with acoustic neuromas. DESIGN: Molecular genetic analysis. SETTING: Molecular genetic research laboratory. PATIENTS: Paired blood-tumor DNA samples were obtained from 43 patients (41 sporadic and two patients with neurofibromatosis type 2). MAIN OUTCOME MEASURES: Loss of constitutional heterozygosity was looked for in the region of tumor suppressor genes on chromosomes 3p, 5q, 11p, 17p, 17q, and 22. RESULTS: We found loss of heterozygosity exclusively for markers on chromosome 22. Thirty-nine percent of tumors showed allele loss, and in each case the loss of heterozygosity included the region of the neurofibromatosis type 2 (NF2) gene. No loss of heterozygosity was detected in the region of known or putative suppressor genes in chromosomes 3p, 5q, 11p, 17p, and 17q. CONCLUSIONS: This study has demonstrated that (1) chromosome 22 allele loss is a frequent event in sporadic acoustic neuroma; (2) the minimal region of loss of heterozygosity in acoustic neuroma includes the NF2 gene; (3) the known tumor suppressor genes investigated (VHL, adenomatous polyposis coli, WT2, p53, and NF1) do not appear to be important in the pathogenesis of acoustic neuroma; and (4) patients with extensive chromosome 22 loss tended to be younger and with a slightly shorter clinical history than those with no detectable allele loss. PMID- 8217083 TI - Transfer of interleukin 2 receptor genes into squamous cell carcinoma. Modification of tumor cell growth. AB - OBJECTIVE: Human squamous cell carcinomas of the head and neck (SCCHN) have been shown to express interleukin 2 receptor (IL-2R), and binding of the ligand, IL-2, to the receptor results in tumor growth inhibition in vitro or in vivo in an SCCHN xenograft model in nude mice. To optimize growth inhibitory effects of IL 2, expression of the alpha or gamma chains of IL-2R in SCCHN was experimentally modified by transfection of tumor cells with the respective IL-2R genes or the lacZ gene as control. DESIGN: Using plasmid vectors containing the IL-2R alpha chain gene under the control of a cytomegalovirus promoter or the IL-2R gamma chain gene under the control of a Rous sarcoma virus promoter, the IL-2R genes were transferred by lipofection into SCCHN cell lines. Stable transfectants were selected, cloned by limiting dilution, and clones were compared with the parental cell lines for their sensitivity to the growth-inhibitory effect of IL-2. RESULTS: Transfer of the IL-2R alpha chain gene into SCCHN cells resulted in significant upregulation of expression of the IL-2R alpha chain on tumor cell surface but not in increased tumor growth inhibition by IL-2. In contrast, SCCHN IL-2R gamma transfectants, which expressed IL-2R gamma chain transcripts as confirmed in RNase protection assays, were significantly inhibited in growth and were sensitive to lower concentrations of IL-2 than the parental cell lines. CONCLUSIONS: Genetic modification of IL-2R expression on IL-2R-positive tumor cells in culture significantly alters their proliferative response to IL-2. These observations open a way for developing new strategies for therapy of SCCHN based on direct interactions of IL-2 with its receptor on tumor cells. PMID- 8217084 TI - Chromosome 11Q13 amplification in head and neck squamous cell carcinoma. AB - OBJECTIVE: To establish the frequency and clinicopathologic correlates of 11q13 amplification in head and neck squamous cell carcinoma. DESIGN: Retrospective clinicopathologic analysis. SETTING: University and private cancer centers. PATIENTS: Eighty-five patients with pathologically confirmed head and neck squamous cell carcinoma. MEASUREMENTS: The degree of DNA amplification in each tumor was determined using chromosome 11q13 probes for the bcl-1 major translocation cluster, PRAD1/cyclin D1 (CCND1), the fibroblast growth factor gene HST1, EMS1, and glutathione S transferase, pi-1. The presence or absence of amplification was correlated with anatomic site, tumor stage, cytologic grade, histologic pattern, and mitotic activity. RESULTS: Thirty-one patients (36%) showed a twofold to 10-fold amplification of 11q13 loci compared with the chromosome 11q23 ETS1 control probe. Twenty-nine of these encompassed bcl-1 through EMS1 loci; one sample showed only bcl-1 and PRAD1/cyclin D1 plus HST1 amplification, with another amplified at HST1 and EMS1 with minimal or no bcl-1 and PRAD1/cyclin D1 amplification. Amplification was significantly correlated with high cytologic grade, a diffusely infiltrative growth pattern, and with a hypopharyngeal primary site. CONCLUSIONS: Chromosome 11q13 amplification in head and neck squamous cell carcinoma is correlated with an aggressive histologic appearance and hypopharyngeal primary site and should be assessed in prospective clinical trials to determine its utility for treatment stratification and prognosis. Although PRAD1/cyclin D1 and EMS1 have been implicated in the pathogenesis of neoplasms with 11q13 amplification, rare cases with more limited amplicon size suggest that another relevant gene or genes may exist between these loci. PMID- 8217085 TI - 44-kd oncofetal transplantation antigen in rodent and human fetal cells. Implications of recrudescence in human and rodent cancers. AB - OBJECTIVE: This article summarizes the phase-specific nature of a cell surface, 44-kd tumor-associated transplantation antigen glycoprotein expressed during early and middle gestation in a portion of rodent and human fetal cells during normal fetal tissue development and illustrates how this glycoprotein is consistently recrudesced in primary and established human squamous cell carcinomas and other human and rodent tumors. The oncofetal antigen was not detectable in any human or rodent term fetal tissue or normal adult tissues tested. The tumor-associated transplantation antigen was tumor specific, yet not germ-line specific (expressed in lymphomas, sarcomas, and carcinomas) in human or rodent cancers. Rodent model tumor studies have shown 44-kd oncofetal antigen can act as a tumor-associated autoantigen of potential use in cancer detection and therapy. DESIGN: The oncofetal antigen was detected by immunogenicity, flow cytometry, and Western blotting in syngeneic rodent tumor recipients and by the last two methods in humans with progressive cancer. Syngeneically derived mouse monoclonal antibody (MoAb 115) was used to identify 44-kd oncofetal antigen. Early to middle gestation, oncofetal antigen-positive, mouse embryo/fetal cells used to stimulate the hybridoma were tested for immunogenicity as a tumor associated transplantation antigen in syngeneic hosts. SETTING AND PATIENTS: Patients presenting with head and neck squamous cell carcinoma (N = 25) and other carcinomas at the University of South Alabama Medical Center, Mobile, underwent a biopsy, and the tumors were mechanically dispersed and were then tested for oncofetal antigen expression directly in flow cytometry. The tumors were also cultured and tested as squamous carcinoma cell lines. Growing squamous carcinoma cells and uncultured tumor cells were stained with MoAb 115 or control MoAb. Extracts of the cells were banded by electrophoresis in gels, Western blotted, and reacted with MoAbs and enzyme-linked immunosorbent assay second antibody. Time-mated mouse fetus and human fetal cells were also stained with MoAb 115 or control antibody and analyzed in the flow cytometer. RESULTS: Eight- to 13-day mouse fetal cells conferred protection against syngeneic tumor challenge. Term 18 to 21-day fetal or neonate or adult mouse cells were nonprotective. All head and neck squamous cell carcinomas tested expressed 44-kd oncofetal antigen by flow cytometric analysis and in Western blots as did ATCC cell lines of these tumors, whereas normal control tissues were negative. Second trimester human fetal cells were 44-kd oncofetal antigen positive. A large spectrum of rodent sarcomas and lymphomas express the OFA. CONCLUSIONS: Shared 44-kd oncofetal antigen OFA offers promise as a tumor detection marker in human squamous cell carcinoma and other human carcinoma development, and syngeneic mouse tumors are good model systems to explore oncofetal antigen antigenicity. PMID- 8217086 TI - Is it time to reassess the pathological criteria for a diagnosis of Alzheimer disease? PMID- 8217087 TI - Alzheimer's disease: empirical evaluation of diagnostic methods. PMID- 8217088 TI - Interlaboratory histopathologic assessment of Alzheimer neuropathology: different methodologies yield comparable diagnostic results. AB - Three investigators have applied different histopathologic methods (modified Bielschowsky silver methods, Congo red-gallocyanin) to differentiate Alzheimer's disease (AD) (n = 7 subjects; four with very mild dementia and three with moderate to advanced dementia) neuropathology from brain changes associated with aging in three nondemented individuals who had been evaluated using a validated dementia severity staging instrument [Washington University Clinical Dementia Rating (CDR)] generally within a year of death. The presence of elevated numbers of neocortical (frontal and temporal) diffuse, mature, and total senile plaques (SP) was strongly correlated with the presence of clinical AD but did not equate with CDR dementia severity. Neocortical neurofibrillary tangle (NFT) density as well as hippocampal NFT and SP density in this small series did not differentiate statistically between AD and controls. NFT density appeared to correlate with CDR better than SP density. Quantitative histopathologic assessment of AD markers in only a few brain regions can accurately predict the presence of clinical AD, including the very mild form of the disease. This is especially true for SP in the neocortex. PMID- 8217089 TI - Clinicopathologic correlates in Alzheimer disease: assessment of clinical and pathologic diagnostic criteria. AB - The neuropathologic findings from a group of 123 patients who have come to autopsy from the Rochester Alzheimer Disease Project (RADP) are presented. Among these 123 cases, there were 94 demented subjects who met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA) clinical criteria for the diagnosis of "probable Alzheimer disease," and 29 normal elderly controls. Autopsy confirmation of Alzheimer disease (AD) was based on the age-graded National Institutes of Health (NIH) consensus conference pathologic criteria. Using the NINCDS-ADRDA clinical criteria and the NIH pathologic criteria, the diagnostic accuracy was 88%, the sensitivity was 98%, and the specificity was 69%. Additional strict clinical and pathologic criteria developed by the RADP were applied in the final review of these cases to exclude all confounding causes of dementia, including cerebral infarcts. After applying these additional criteria, a subset of 62 cases of "pure" AD and "pure" control subjects was identified for a more detailed examination of neuritic plaques (NP) and neurons containing neurofibrillary tangles (NFT). The NP and NFT were counted in three subfields of hippocampus and two areas of association neocortex. The density of diffuse plaques (plaques lacking dystrophic neurites) was estimated on a semiquantitative basis. Results show that the AD patients and control groups could be distinguished from each other easily on the basis of mean NP and NFT counts, but there was sufficient overlap in the counts to present difficulty in diagnosing any individual case. Abundant diffuse plaque involvement and NFT in the neocortex were, however, seen only in AD cases. PMID- 8217090 TI - Advancing research with Alzheimer disease subjects: investigators' perceptions and ethical issues. AB - Advancement of Alzheimer disease (AD) research will not only depend on increased participation of patients with AD as subjects, but researchers will likely face increasingly difficult ethical issues. Presented are the results of a survey of researchers at the 15 federally funded Alzheimer Disease Research Centers concerning the ethical issues for subjects with AD participating in research. Experiences from 99 projects are assessed. Major findings include a significant lack of uniformity on the assessment of competency of subjects to consent to research, proxy informed consent overwhelmingly provided informally by family members, no wide use of durable powers of attorney and guardians, perception by the investigators that most projects present only minimal risks to the subjects, and Institutional Review Boards not being viewed by the investigators as preventing or inhibiting the advancement of AD research. It is recommended that research is needed to develop greater clarity in assessment of capacity of subjects to provide informed consent, that ethical and legal empowerment of family members to provide proxy consent be sustained, and that the issue of risk/benefit ratios for AD participants in research be reevaluated in the light of potentially greater risks to subjects. PMID- 8217091 TI - Effects of light on mood. PMID- 8217092 TI - Human circadian rhythms: lessons from the blind. PMID- 8217093 TI - Polycystic ovary syndrome: long-term effects. PMID- 8217094 TI - Glaucoma: changes in extracellular matrix in the optic nerve head. AB - Primary open angle glaucoma (POAG), the most common form of glaucoma, is characterized by irreversible loss of axons from the optic nerve. The site of damage to the axons is at the level of the lamina cribrosa in the optic nerve head. It has been hypothesized that structural and biochemical abnormalities in the extracellular matrix (ECM) of the lamina cribrosa underlie the progressive compressive and remodelling of this connective tissue in glaucoma. In this review, we present evidence of specific changes in collagen and elastic fibers, major ECM components in the lamina cribrosa of glaucomatous eyes. PMID- 8217095 TI - Approaches to the genetics of affective disorders. AB - Affective (mood) disorders are common. There are several methodological impediments to genetic studies of affective disorders, including uncertainties about the best definition of disease phenotype, difficulties in the assessment of lifetime diagnosis and variable age of onset of illness. Despite these difficulties, family, twin and adoption studies provide compelling evidence for the existence of important genetic factors in determining susceptibility to affective disorders. However, the mode of inheritance is unknown. Simple mendelian inheritance may occur in some families but cannot explain the majority of cases. With the advent of polymorphic DNA markers, linkage and association studies have become more useful methods for the genetic analysis of complex disorders such as affective illness. No consistent finding has yet emerged, although chromosomal region 11p15 (and to a lesser extent Xq28) are of continuing interest. In addition to further study of these regions it will also be necessary to look for susceptibility loci in other parts of the genome. Large samples will almost certainly be required. If susceptibility loci of major effect exist then linkage approaches will find them. However, if there are only loci of small effect, then association approaches will be necessary. At present, it seems prudent to pursue both linkage and association approaches together. PMID- 8217096 TI - The diagnosis and treatment of gastro-oesophageal reflux disease in infants and children. AB - Gastro-oesophageal reflux is a common phenomenon in infants, and is an aspecific complaint. The balance between negligence and overconcern is therefore very difficult to make, and requires experienced physicians. The approach in infants with uncomplicated reflux consists of non-drug treatment and reassurance of the parents about the almost physiological nature of the regurgitations of the baby. If the parents persist in their complaints, the administration of prokinetics such as cisapride can be considered before performing investigations (oesophageal pH monitoring). The efficacy and the lack of side-effects of cisapride makes this the drug of choice. The frequency of side-effects of other drugs necessitates the diagnosis of reflux disease before their administration. Upper gastrointestinal tract endoscopy is the investigation of choice in children suspected of reflux oesophagitis. In the majority of cases, the efficacy of cisapride, H2-blockers and Na-K-ATP-ase-blockers should be given a chance. Unusual presentations, such as chronic respiratory disease, as a manifestation of reflux disease should be confirmed with oesophageal pH monitoring. PMID- 8217097 TI - Herpes virus infections in immunocompromised patients: problems and therapeutic interventions. AB - Herpes virus infections are responsible for morbidity and mortality among immunosuppressed patients. During the last decade substantial advances have been achieved through improvement of diagnostic techniques, development of effective antiviral agents and the use of different strategies for prophylaxis and treatment. Cytomegalovirus infection and disease can today be prevented and treated effectively; however, antiviral resistance is beginning to emerge as a potential major clinical problem. Similarly, infections with herpes simplex virus and varicella-zoster virus can be effectively treated, but antiviral resistance has also emerged for these viruses. Two new herpes viruses, human herpes viruses 6 and 7, have been discovered, and it is possible that these viruses can also cause significant problems in immunosuppressed individuals. New antiviral agents will be needed during the next decade to allow further advances in the treatment of herpes virus infections. PMID- 8217098 TI - Integrin-type extracellular matrix receptors in cancer and inflammation. AB - The integrins are a large family of cell adhesion receptors, involved in cell cell and cell-matrix interactions. At present, 20 different integrin heterodimers are known. Integrins participate in a complex apparatus anchoring cells to their surroundings and transducting signals into the cells. These signals regulate many important aspects of cell behaviour, including growth, differentiation, and phenotype. This is an overview of the molecular and cellular biology of the integrin-type extracellular matrix receptors. Integrins may play a central role in the healing process of tissue injuries, and in many diseases, especially in human cancer. PMID- 8217099 TI - Cytokines in reproduction. AB - A growing body of evidence indicates that, in addition to the hormones of hypothalamic, pituitary and gonadal origin, autocrine/paracrine regulators play important roles in the reproductive functions. Cytokines, originally known as immunoregulatory proteins, may affect the neuroendocrine events of reproduction, ovarian/testis function, endometrium, the developing embryo, placenta and parturition. Cytokines can modulate and mediate the actions of hormones at their target cells and, in the opposite way, hormones may regulate the production and action of cytokines at three different levels: cytokine secretion, cytokine receptor expression and cellular responses. Cytokines may also function in an endocrine manner affecting distant targets. As many of the cyclic changes that occur in the ovary and endometrium during the normal menstrual cycle are similar to those associated with the inflammatory and regenerative processes, it is likely that cytokines are involved in these reactions. Furthermore, cytokines secreted by endometrial white blood cells may influence embryo development and trophoblast growth and may play a fundamental role in the mechanisms of immunological reproductive failure. Cytokines have also been implicated in the mechanisms responsible for the onset of parturition. PMID- 8217100 TI - Late Lyme borreliosis: epidemiology, diagnosis and clinical features. AB - Lyme borreliosis is endemic in the Aland Islands. Exposure of the inhabitants to bites of the tick Ixodes ricinus is heavy. The purpose of this study was to describe symptoms and signs of patients with late Lyme borreliosis in this area, and to correlate the findings with the epidemiological setting. The first 100 consecutive patients with late Lyme borreliosis found in the region since 1984 are included in this study. Neurological, articular and muscular symptoms and signs dominate. General screening for Lyme disease is not recommended in the area due to uncertainty about how to deal with seropositive healthy persons in this heavily exposed population. The recognition and prompt treatment of erythema migrans and other manifestations of primary Lyme borreliosis is important in order to avoid the late stages of the disease. Treatment of all those suffering tick-bites with an antibiotic would be an option in view of the incidence of infected ticks, but cannot be considered because tick-bites are extremely common among the inhabitants. The region would be suitable for general immunization against Borrelia burgdorferi if the means for doing this becomes available in the future. PMID- 8217101 TI - Mechanism of bone turnover. AB - Bone remodelling is a cellular mechanism behind the bone turnover. It renews the old bone piece by piece and thus ensures the correction of possible microdamage and enables the regulation of mineral homeostasis. The basic mechanism of bone remodelling is similar in all types of bone and includes the resorption of old bone and the formation of equal amount of new bone at the same place. Histomorphometric studies have revealed the cellular details of remodelling and have shown that it is composed by the temporally and spatially regulated action of different bone cells and their precursors. Recent in vitro studies with osteoclasts and osteoblasts have increased our knowledge of the molecular mechanisms of bone remodelling. Molecular characterization of bone matrix proteins have suggested new functions to many of them and thereby increased our possibilities of understanding the local regulation mechanisms of remodelling. Bone matrix has been shown to contain several biologically active compounds which have effects on bone forming and resorbing cells and their precursors. Details of the functional mechanism of osteoclasts are also in the process of being discovered. However, several questions concerning bone remodelling still remain open: the molecular explanation for selection of the remodelling site; the coupling of bone resorption to formation, and the interactions between different cell types during the remodelling cycle. PMID- 8217102 TI - Oestrogen effects on osteoblasts and osteoclasts. AB - Although it has been recognized for many years that oestrogen is a key component in the maintenance of normal bone balance, the mechanisms by which oestrogen exerts its influence have remained unresolved. Recent identification of oestrogen receptors in both bone-forming osteoblasts and bone-resorbing osteoclasts has opened up exciting new areas of research on the direct effects of oestrogen on both osteoblasts and osteoclasts. This review presents an updated model for the molecular mechanisms involved in oestrogen action, the mechanism of anti oestrogen action, and outlines recent advances in knowledge of oestrogen effects on osteoblasts, osteoclasts, and the coupling of bone resorption and bone formation. PMID- 8217103 TI - Bisphosphonates in the treatment of metabolic bone diseases. AB - Bisphosphonates (BP) are pyrophosphate analogs, P-C-P with various carbon side chains. The phosphate groups are responsible for the low gastrointestinal absorption (about 1%), limited penetration into cells, adsorption to bone mineral and rapid excretion in the urine. Based on the C side-chains, BPs can inhibit osteoclastic bone resorption with potencies which differ by as much as 10,000 fold among compounds. The most potent inhibitors are aminobisphosphonates. Studies of the amino-BP alendronate show preferential uptake at sites of bone resorption where they block osteoclastic activity by inhibiting ruffled border formation. BPs are the treatment of choice for hypercalcaemia of malignancy, where a single infusion with a potent BP will normalize serum calcium in 80% of the patients. Paget's disease also shows an excellent long-term response to BPs. In addition, BPs are being studied for the treatment of osteoporosis and other bone disorders which could be helped by inhibition of bone resorption. PMID- 8217104 TI - Nutritional rickets: thoughts about pathogenesis. AB - The pathogenesis of nutritional rickets is not well-understood. While the etiologies include deficiencies of vitamin D, calcium (Ca) or phosphate (PO4), and perhaps aluminium toxicity, the role these nutrients play in the development of tissue level anomalies characteristic of rachitic cartilage and bone has yet to be defined. Reported alterations in the biochemistry of rachitic bone and cartilaginous matrix which could adversely affect mineralization and endochondral ossification are of questionable significance since the tissues mineralize rapidly when exposed to Ca and PO4 salts in vivo and in vitro. The low Ca and PO4 concentrations of the extracellular fluid (ECF) bathing rachitic cartilage and bone matrix suggest that local mechanisms operate to impair mineralization. In healing rickets, the Ca and PO4 content of these tissue fluids increases in the same time-frame it takes to experimentally remineralize the matrices. However, it is not certain what determines the Ca and PO4 content of the ECF. Cytokines which may play a role in the cellular regulation of Ca and PO4 and maintain processes which contribute to normal patterns of endochondral ossification could provide a mechanism common to the pathogenesis of rickets from a variety of causes. PMID- 8217105 TI - Biochemical markers of bone metabolism. AB - In this article we review the biochemical basis for markers of bone metabolism and comment on their bone specificity and representativeness for bone tissue. Major developments have recently taken place particularly with respect to markers of bone collagen metabolism; accordingly, they are in the focus of this review. We also attempt to relate the various collagenous and non-collagenous markers to each other and to the phases of the osteoblast phenotype. PMID- 8217106 TI - Osteoinductive proteins. AB - Cartilage and bone tissues are rich in different polypeptide factors (growth factors) which participate in the regulation of skeletal development and growth. Parallels between the embryonal endochondral ossification, callus formation during fracture repair, and ectopic bone induction in postnatal life have encouraged scientists to search for common mechanisms underlying these processes. A set of polypeptide factors belonging to the TGF-beta superfamily called the bone morphogenetic proteins (BMPs), have been found to be of fundamental importance both in bone formation and mesenchymal-epithelial interactions in early embryogenesis. Thus, this group of proteins is a common denominator in all the above-mentioned processes involving osteoinduction and there is great potential for their clinical application as bone-inducing factors. PMID- 8217107 TI - Clinical use of bone allografts. AB - Modern techniques of bone allograft surgery provide a treatment modality for management of difficult skeletal defects. In oncological limb-salvage surgery, allograft reconstructions permit re-establishment of skeletal continuity and function after a wide resection of bone tumour. Bone allografts are increasingly used in salvage of difficult bone stock deficiencies following failed total joint replacements. Union between the allograft and the host bone takes place slowly and the use of autogenous bone graft at the graft-host junction is recommended for induction of repair. Internal repair (revascularization and substitution of the original graft bone with new host bone) also progresses slowly and seems to be confined only to the superficial surface and the ends of the graft. Biomechanically, a massive allograft may serve a structural function in the absence of advanced revascularization and creeping substitution processes. Infection of an allograft is a disastrous complication, whereas non-union of the graft-host junction and fracture of the graft are amenable to surgical treatment. Osteochondral allografts tend to show gradual deterioration of the articular cartilage with time, necessitating occasionally late resurfacing arthroplasty. It is evident that there is more active immune response to osteochondral grafts than was thought previously. Bone allografts induce cell-mediated and antibody mediated cytotoxicity specific for donor antigens similar to that seen after organ transplantations. Not only the basic mechanisms of bone allograft rejection but also the clinical features of bone allograft rejection are poorly characterized. Clinically, new non-invasive imaging techniques should be applied in determining the metabolic activity of bone in order to find the optimal loading of healing allografts. Although the clinical results of massive bone allografts are still not completely predictable, the method has proved to be a technically and biologically feasible alternative for non-biological skeletal reconstructions. PMID- 8217108 TI - Bone and the 'comforts of life'. AB - Coffee drinking, smoking and especially alcohol abuse are considered to be risk factors for fractures and osteoporosis. Caffeine causes acute increase in urinary calcium excretion, but epidemiological evidence for the effects of coffee consumption on the risk of fractures is contradictory. Many, (but not all) studies point to decreased bone mass or increased fracture risk in smokers. Alcohol abuse is associated with deleterious changes in bone structure detected by histomorphometry, and with a decrease in bone mineral density (BMD). These changes may also be produced by factors commonly associated with alcohol abuse, e.g. nutritional deficiencies, liver damage and hypogonadism. Alcohol, however, has clear-cut direct effects on bone and mineral metabolism. Acute alcohol intoxication causes transitory hypoparathyroidism with resultant hypocalcaemia and hypercalciuria. As assessed by serum osteocalcin levels, prolonged moderate drinking decreases the function of osteoblasts, the bone-forming cells. In addition, chronic alcoholics are characterized by low serum levels of vitamin D metabolites. Thus, alcohol seems to have a direct toxic effect on bone and mineral metabolism. In contrast, it has recently been reported that moderate alcohol consumption by postmenopausal women may have a beneficial effect on bone. PMID- 8217109 TI - Formation of trifluoroacetic acid from the atmospheric degradation of hydrofluorocarbon 134a: a human health concern? PMID- 8217110 TI - Reduction of E. coli adherence to rubber slices treated with phospholipids. AB - The present study aimed at modifying the surface of biliary drain material to reduce bacterial adherence. The adherence of cells of seven E. coli strains to rubber slices treated with phosphatidylcholin (PC) or phosphatidylinositol (PI) and the adherence of cells of E. coli strain NG7C to PC- or PI-treated rubber slices implanted in the common bile duct in rats were studied in vitro. The rubber slices were incubated with 1 x 10(7) cfu radiolabeled E. coli cells/ml at 37 degrees C for 60 min and then drained and washed thrice in 2 ml PBS, and adherent E. coli cells were quantified by radioactivity counting. The results show that both PC and PI absorbed on the surface of slices reduced the adherence of E. coli cells in at least two ways, i.e. by changing surface properties in vitro and by reducing deposition of host-derived molecules on phospholipid treated surfaces in vivo. The results may be of use for modification of the biomaterial surface in the clinical situation. PMID- 8217112 TI - Theoretical aspects of detection of bacteraemia as a function of the volume of blood cultured. AB - Clinically significant bacteraemia in adults is characterized by low numbers of circulating bacteria. Assuming a Poisson or a binomial distribution we have calculated the probability of detecting bacteria as a function of the concentration in blood, estimated the concentration of bacteria in blood from a given test result, and calculated the blood volume required to detect bacterial growth with a probability of 95% at a given mean number of colony-forming units (cfu) per sample unit. These theoretical assumptions have been used on an empirical population of patients with proven bacteraemia. RESULTS: 18% of Staphylococcus aureus bacteraemias and 29% of Escherichia coli bacteraemias have circulating bacteria with an estimated spread of less than 0.04 cfu/ml. With a 95% probability of detection of a bacteraemia, a concentration in blood corresponding to 3 cfu/sampling unit is necessary. In our empirical material, where 30 ml was cultured, the probability of detection of E. coli bacteraemias would have decreased by 11% if 20 ml had been cultured, and 27% if only 10 ml had been cultured. The corresponding figures for S. aureus were 6% and 15%, respectively. For low grade E. coli bacteraemias (< 0.04 cfu/ml) the decrease would have been 33% and 67%, respectively. PMID- 8217111 TI - Evidence for a primarily humoral rejection mechanism in concordant xenogeneic heart transplantation. A sequential immunohistological study in a hamster-to-rat model. AB - Heterotopic heart transplantations in an unmodified hamster-to-rat model were studied sequentially by immunohistochemical analysis. Monoclonal mouse anti-rat antibodies against B cells, T cells, macrophages and neutrophilic granulocytes (MRC OX-19, MRC OX-38, MRC OX-8, MRC OX-22, MRC OX-33, MRC OX-41 and MRC OX-42) were used in an indirect immunoperoxidase technique and monoclonal mouse anti-rat IgM and IgG were used for immunofluorescence. In grafts investigated after 6 h (N = 8) minimal infiltration of macrophages was demonstrated with MRC OX-41+ and MRC OX-42+ cells. No T- or B cells were seen. In a few cases, deposition of IgG and IgM was seen related to the endothelium of larger vessels. In grafts examined 24 h after transplantation (N = 10) the number of MRC OX-41+ and MRC OX-42+ cells had increased and in half of the cases IgM and IgG were located in relation to endothelial cells of larger vessels. In grafts investigated 48 h after transplantation (N = 8) the infiltration with MRC OX-41+ and MRC OX-42+ cells had further increased and a few scattered MRC OX-19+ and MRC OX-8+ cells appeared. At this time all but one heart had deposition of IgG and IgM in the vessel walls. Upon complete rejection (N = 8) diffuse infiltration of MRC OX-41+ and MRC OX-42+ cells was seen, but still only a few scattered T cells could be demonstrated. At this time IgG an IgM deposition appeared in all vessels and was also located in relation to the capillaries. These results further support our hypothesis that acute xenograft rejection in this animal model is primarily of the humoral type. PMID- 8217113 TI - Microinjection of HEp-2 cells with coxsackie B1 virus RNA enhances invasiveness of Shigella flexneri only after prestimulation with UV-inactivated virus. AB - Coxsackie B1 virus induces increased susceptibility to invasion by Shigella flexneri when HEp-2 cells are inoculated with the complete virus. When RNA from the same virus was microinjected into cells, virus RNA was synthesized and new virus particles were formed, but the transfected RNA had no effect on bacterial invasiveness. However, when the cells were prestimulated with UV-inactivated virus, the microinjected RNA induced an additional enhancement of bacterial invasiveness. Microinjected whole virus particles did not replicate and did not induce any change in bacterial invasiveness. The results indicate that an initial event in virus multiplication is necessary to achieve an effect of transfected viral RNA on invasion of S. flexneri. PMID- 8217114 TI - Histological grade, DNA ploidy and mean nuclear volume as prognostic factors in prostatic cancer. AB - Seventy-nine consecutive patients with prostatic cancer diagnosed between 1979 and 1983 were classified with respect to histological grade according to Shelley et al. (23), DNA ploidy (diploid, tetraploid and aneuploid), and mean nuclear volume (mnv) of the cancer cells. Nine patients were still alive at the time of analysis (minimum observation time 7.5 years). Univariate analysis showed that histological grade (p = 0.004), DNA ploidy (p = 0.0002) and mnv (p = 0.009) all had a significant influence on crude survival. A Cox proportional hazards model was used to analyse the prognostic value of these factors and patient age. However, when the two strongest of these four factors, histological grade (p = 0.0025) and DNA ploidy (p = 0.0035), were corrected for, age (p = 0.07) and mnv (p = 0.22) had no independent impact on crude survival. PMID- 8217115 TI - Gastrointestinal non-Hodgkin's lymphoma. A population-based clinicopathological study of 111 adult cases with a follow-up of 10-15 years. AB - All cases of gastrointestinal (GI) non-Hodgkin's lymphoma diagnosed in Finland between 1972 and 1977 were histologically reexamined and immunostained in order to study the value of histological classification. One hundred and eleven cases were found. The crude annual incidence was 0.51/10(5) and the age-adjusted (world standard population) incidence 0.23/10(5). The male-to-female ratio of age adjusted incidence rates was 2.7. The most common histological type was large B cell lymphoma comprising 61% of all classifiable cases. Low-grade mucosa associated lymphoid tissue (MALT) lymphoma comprised 12%, centrocytic lymphoma 9%, peripheral T-cell lymphoma 9%, Burkitt's lymphoma 7% and large-cell anaplastic lymphoma 3% of the total. In the jejunum, almost one half of the cases were T-cell lymphomas and there were no lymphomas with definite MALT features. Gastric lymphomas had higher survival rates than intestinal lymphomas, B-cell lymphomas slightly higher survival rates than T-cell lymphomas, and low-grade MALT lymphomas higher survival rates than other B-cell lymphomas. The other types of lymphomas differed only slightly from each other in prognosis. The histological grade according to the Working Formulation correlated with survival rates, but a great majority of cases were classified as intermediate grade. Classification of GI lymphomas into the types mentioned above appears to correlate with several clinical and pathological parameters. PMID- 8217116 TI - Comparison of various methods and reagents for species identification of Staphylococcus aureus positive or negative for the mecA gene. AB - The reliability of various methods for species identification of Staphylococcus aureus was evaluated. A total of 135 coagulase-positive (SA) or -negative (SS) staphylococcal isolates were tested, including methicillin-resistant (MR) and susceptible (MS) strains. When the nuc gene which encodes the S. aureus thermonuclease (TNase) was amplified in a multiplex PCR simultaneously with the mecA gene which encodes for the MR-associated penicillin-binding protein 2a of staphylococci, the nuc amplification showed full agreement with the results of the coagulase test. TNase detected by an enzymatic method or as protein in a sandwich ELISA identified S. aureus with nearly the same precision as the PCR. The Staphylase, Monostaph and Staphaurex agglutination kits were all reliable for identification of MSSA, but not for MRSA. Most of the negative MRSA strains were identified by the Pastorex agglutination kit, in which reagents for fibrinogen receptor and protein A detection have been supplemented with antibodies for capsular polysaccharides of the serotypes 5 and 8. These results show that detection of the nuc gene or its TNase product is highly reliable for identification of both MRSA and MSSA strains, while various widely used agglutination kits do not show the same reliability for identification of MRSA strains. PMID- 8217117 TI - Assay of pertussis vaccine reactivity factors by measurement of the paw swelling response, endotoxin and histamine-sensitizing factor. AB - Bordetella pertussis is composed of a series of active components: (1) a heat labile or dermonecrotic toxin (HLT); (2) a lipopolysaccharide endotoxin (LPS); (3) pertussis toxin; (4) filamentous hemagglutinin (FHA); (5) agglutinogens; (6) outer membrane proteins; (7) adenylate cyclase; and (8) tracheal cytotoxin. Pertussis toxin (PT), also called lymphocytosis-promoting factor (LPF), encompasses a series of biological activities including: (1) histamine sensitization (HSF); (2) leukocytosis-promoting activity (LPF); (3) LPF hemagglutinin (LPF-HA); and (4) pancreatic islet-activating protein (IAP). The heat-labile toxin is inactivated during vaccine production. Pertussis toxin is inactivated when heated to 80 degrees C for 30 min and endotoxin at a temperature greater than 120 degrees C for 30 min. The effect of pre- and post-heat treatment on DTP vaccine, Bordetella pertussis endotoxin, pertussis toxin and a pertussis toxin/endotoxin combination, was determined as related to: (1) paw swelling response; (2) LAL activity (endotoxin); and (3) HSF activity. With the exception of DTP and B. pertussis endotoxin, the average paw swelling response after injection of non-treated and heat-treated test samples was similar to the saline control at all measured time intervals. Contrary to anticipated results, heat treatment enhanced the paw-swelling response of DTP vaccine and B. pertussis endotoxin. Endotoxin levels, as measured by LAL, were significantly lower after heat-treatment, with the exception of B. pertussis endotoxin and the E-1 control. The addition of pertussis toxin, B. pertussis endotoxin or pertussis toxin/endotoxin did not restore LAL values to the levels seen for non-treated DTP vaccine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217118 TI - Comparative studies of the in vivo toxin neutralization and the in vitro Vero cell assay methods for use in potency testing of diphtheria component in combined vaccines/toxoids. 1: Standardization of a modified Vero cell assay for toxin antitoxin titration of immunized guinea-pig sera. AB - The in vivo Toxin Neutralization (TN) test is currently used as an antibody limit test for regulatory control testing of diphtheria potency in combined vaccines/toxoids. This test requires the use of guinea-pigs for estimating diphtheria antitoxin titre in immunized sera. The acceptability criteria (minimum requirement) for adsorbed pediatric vaccines/toxoids in the TN test are the production of at least 2.0 IU/ml of antitoxin in the serum pool of immunized animals. The feasibility of employing the in vitro Vero cell assay as an alternative limit test to the TN test was investigated. Parallel titration of serum samples from guinea-pigs immunized with DPT (ads) vaccine (pediatric use) showed that although the in vitro antitoxin titre paralleled the in vivo values, a direct correlation between the two methods could not be established. The mean in vitro titres were lower (in terms of IU/ml) than those obtained by the in vivo TN test. This could possibly be explained by the differences between reference serum which is a hyperimmune horse serum and the test sera which are from guinea pigs which have been immunized only once. The in vitro/in vivo ratio of the antitoxin titre ranged from 0.1 to 0.24 IU/ml with a mean value of 0.17 (SD, 0.06). Hence, for pediatric vaccines, a tentative in vitro limit of 0.3 IU/ml, which would correspond to the currently required limit of 2.0 IU/ml in the in vivo TN test, could be accepted as the minimum requirement for the antitoxin titre in the Vero cell assay. PMID- 8217119 TI - Transmissible spongiform encephalopathies and the safety of naturally-derived biologicals. AB - Late in 1986, a new neurodegenerative disease, referred to as bovine spongiform encephalopathy (BSE), was recognized in domestic cattle in southern England. Since then, tens of thousands of cases have been confirmed throughout the U.K. and the disease has also appeared sporadically outside of the British Isles. BSE belongs to a group of rare, progressive and fatal disorders of the central nervous system of animals and man caused by anomalous infectious agents whose properties are not yet full understood. Consequently, fears were raised about the possibility that the disease might constitute a possible health risk for humans. Minimization of potential contamination has thus become an issue of growing interest. This short review summarizes the main aspects of the problem together with the procedures developed to sterilize preparation of biologicals even from sources containing potentially high levels of contamination. PMID- 8217120 TI - The First International Standard for Antitetanus Immunoglobulin, Human; pharmaceutical evaluation and international collaborative study. AB - The First International Standard (IS) for Antitetanus Immunoglobulin, Human (coded 26/488) was established by the WHO Expert Committee on Biological Standardization in October 1992 on the basis of an extensive pharmaceutical evaluation and an international collaborative study. Fifteen laboratories from 15 countries performed the toxin neutralization assay in vivo in the study. Twelve laboratories also performed an alternative in vitro assay. The new International Standard is a purified human immunoglobulin containing antibodies which are able to neutralize tetanus toxin. This new standard replaces the Second International Standard for Tetanus antitoxin, Equine, for testing of human antitetanus immunoglobulin preparations used clinically as well as for titration of human serum samples for tetanus antitoxin. The new International Standard was assigned a potency of 120 International Units (IU) of Tetanus Antitoxin per ampoule on the basis of its calibration in terms of the International Unit defined by the Second International Standard for Tetanus Antitoxin, Equine by toxin neutralization assay in vivo. The same preparation was also established as the first European Pharmacopoeia Standard for Antitetanus Immunoglobulin, Human by the European Pharmacopoeia Commission, Biological Standardization Programme in March 1993. PMID- 8217121 TI - Biological potency standards for cytokines and growth factors. PMID- 8217122 TI - Supplement to the points to consider in the production and testing of new drugs and biologicals produced by recombinant DNA technology: nucleic acid characterization and genetic stability. PMID- 8217123 TI - Virological safety aspects of plasma derivatives. November 1992, Cannes, France. PMID- 8217124 TI - Central determinants of attention and mood disorder in tardive dyskinesia ("tardive dysmentia"). AB - The typical apathetic state of tardive dyskinesia patients may be punctuated by periods of hyperactivity, vigilance, and tension. Patients may exhibit unusual readiness for contact, even though they remain edgy, loud and loquacious, euphoric, jolly, intrusive, and invasive of the privacy of others. These features designated as "tardive dysmentia" are examined, so as to draw attention to the possibility that the syndrome of dysmentia is comprised of occasional excessive emotional reactivity, enhanced responsiveness to environmental stimuli, and indifference to or reduced awareness of the patient's abnormal involuntary movements. The pathophysiology of tardive dysmentia remains uncertain. It is proposed that behavioral changes in patients with dysmentia may be conceived in terms of a more outward direction of attentional processing. Such an immense change in psychopathology under antipsychotic drugs, from withdrawal to the emotional externalization of behavior, is conceived as reflecting a shift in the approach-avoidance behavior due to alterations in the parieto-frontal balance. PMID- 8217125 TI - Ionomer-based bone substitute in otologic surgery. AB - During post-set hardening the self-curing bone substitute Ionocem develops a solid bond with the adjacent bony tissue, leaving no empty spaces. The fully matured material can be fixed to bone with freshly mixed cement or it may be used as a blank, e.g. an ossicular implant (Ionos ossicle). After insertion of 945 alloplastic middle ear prostheses over a period of 4.5 years, the take-rate was 94%. In some patients revision surgery became necessary, in 50% of cases because of prosthesis dislocation. A granular version of the cement (Ionogran) was implanted in 46 ears for obliteration of mastoid cavities and showed complete mucosal overgrowth within a maximal period of 3 months. Posterior canal wall reconstruction with the self-curing bone substitute was done in 74 patients, with revisions required in 12 cases because of persistent epithelial deficits in the external ear canal or epitympanic retraction. Overall results showed that the ionomer-based cement was a useful substitute for bone in reconstructive otologic surgery. PMID- 8217126 TI - Inner ear morphology in CBA/Ca and C57BL/6J mice in relationship to noise, age and phenotype. AB - CBA/Ca mice showing moderate hearing losses with onset late in life and C57BL/6J mice with progressive hearing losses starting when animals were young adults were exposed to a 2-7 kHz, 120 dB SPL noise band for 5 min in order to investigate morphological consequences to noise as a function of age and genotype. Permanent threshold shifts were determined by auditory brainstem responses 1 month after noise exposure at 1, 3 and 6 months of age. CBA mice had a decreasing susceptibility to noise with increasing age, while C57 mice remained equally susceptible throughout all ages tested. The threshold shifts were then analyzed in relation to morphological changes of the organ of Corti as visualized by light microscopy (LM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). CBA mice exposed at 1 month and sacrificed at 2 months had seemingly normal cochlear morphologies under LM. In these animals SEM findings demonstrated mild stereocilia damage to noise trauma, but not when mice were exposed at 3 and 6 months. There was no visible morphological aging of hair cells found during the period tested. In contrast, the C57 mice had early hair cell changes including bent and fused stereocilia, bulging of the cuticular plates, hair cell loss and swelling of afferent dendrites. These changes became more pronounced throughout the test periods with the variability of damage in this strain more evident over time. This pattern was also aggravated in all C57 age groups tested after noise exposure. Quantification with cytocochleograms demonstrated a statistically different reaction pattern to noise trauma between the two different genotypes of mice. PMID- 8217127 TI - Dynamics of Na,K-ATPase sites in lateral cochlear wall tissues of the rat. AB - The objective of this study was to determine whether varying levels of either the synthetic glucocorticoid, dexamethasone, or the mineralocorticoid, aldosterone, modulate the quantity of Na,K-ATPase sites in stria vascularis and spiral ligament tissues. Surgically adrenalectomized male rats were administered different dosages of dexamethasone or aldosterone for 7 days and subsequently were sacrificed. Na,K-ATPase alpha-subunits of stria vascularis and spiral ligament homogenates were determined quantitatively by enzyme-linked immunosorbent assay, using a monoclonal antibody shown to react with lateral wall Na,K-ATPase alpha-subunit. Elevated serum levels of dexamethasone were correlated with significantly increased Na,K-ATPase alpha-subunit levels in both the stria vascularis and spiral ligament (P < 0.05). Elevated serum levels of aldosterone were correlated with increased Na,K-ATPase alpha-subunits in the stria vascularis, but not in the spiral ligament (P < 0.1). These data further indicate a positive correlation between increased serum levels of adrenal steroids and induction of Na,K-ATPase synthesis by such steroids, particularly by dexamethasone. PMID- 8217128 TI - A comparison of bilateral and unilateral botulinum toxin treatments for spasmodic dysphonia. AB - To assess the efficacy of bilateral or unilateral botulinum treatments for spasmodic dysphonia we injected botulinum toxin (type A) into the thyroarytenoid muscle of 24 patients with adductor type spasmodic dysphonia. Eleven patients underwent unilateral procedures and 13 bilateral procedures. Samples of sustained phonation were analyzed acoustically by a computer-assisted method and the air flow rates determined. All tests were conducted 1 week before injection and 1 week and 1 month after treatment. With unilateral injection, improvements in acoustic parameters occurred as early as 1 week after treatment. With bilateral injections, only the voice break factor was significantly reduced after 1 week, while standard deviations of fundamental frequency, jitter, shimmer and signal-to noise-ratios were reduced 1 month after treatment. In comparison with unilateral injections, the mean air flow rate was twice as high 1 week after bilateral injections, with no significant differences found 1 month after treatment. Clinically, both injection modes resulted in the reduction of laryngeal spasms as early as within 48 h after injection. PMID- 8217129 TI - An association of the RB gene with osteosarcoma: molecular genetic evaluation of a case of hereditary retinoblastoma. AB - A 24-year-old male patient with hereditary retinoblastoma and a poorly differentiated osteoblastic osteogenic sarcoma was found to carry a mutant RB1 allele in all cells. This findings was most likely a point mutation or microdeletion because Southern blot analysis of peripheral blood DNA failed to disclose any structural aberration of the RB1 gene. A somatic mutation (deletion) affecting the other allele was found in the osteosarcoma cells. Management of tumor by external radiotherapy in early age is questioned because the effect of irradiation is to significantly increase the total incidence of second tumors above the already high incidence in non-irradiated patients. PMID- 8217130 TI - Intensity-related changes in cochlear blood flow in the guinea pig during and following acoustic exposure. AB - This study examined the effects of acoustic exposure at different intensities on cochlear blood flow (CBF) using laser Doppler flowmetry. CBF was measured in anesthetized guinea pigs exposed to either a 10 kHz pure tone at 125, 105, or 90 dB SPL, or wide-band noise at 85 dB SPL for 1 h. Mean arterial blood pressure and heart rate were recorded continuously. Arterial acid-base status, cochlear temperature, cochlear microphonics (CM), and compound action potentials (CAP) were measured before and after exposure. There was a small, but significant, steady decline in basal CBF after 40 min loud sound exposure (125 dB SPL), but no change in basal CBF occurred with the lower intensities (85-105 dB SPL). In contrast, there was a significant increase in apical CBF after 1 h exposure to either moderate wideband noise (85 dB SPL) or a 10 kHz tone at 105 dB SPL. These changes persisted during a 20-min post-exposure period. In most cases, the cochlear temperature and cardiorespiratory variables monitored remained unchanged during and after the exposures as compared to the controls. CM and CAP amplitudes showed extensive losses after acoustic overstimulation (125 dB SPL), but no permanent changes were found at the lower intensities used. The present findings confirm the occurrence of intensity-related effects of acoustic exposure on the cochlear microcirculation. PMID- 8217131 TI - Effect of climatic elements on the frequency of secretory otitis media. AB - A relationship between the number of children hospitalized for secretory otitis media and climatic elements was observed during a 10-year period (1981-1990). The highest correlation was obtained between the number of secretory otitis media cases and the number of sunny hours in a month, followed by that between the number of secretory otitis media cases and the mean monthly temperature and relative air humidity. The largest number of children were hospitalized for secretory otitis media toward the end of winter, and the lowest toward the end of summer (in August and September). PMID- 8217132 TI - Defective monocyte chemotaxis in patients with epidermoid tumors of the head and neck. AB - Monocyte chemotactic activity was assayed by a modified Boyden-Chamber method using the chemoattractant casein and was found to be impaired in 13 patients with epidermoid tumors of the head and neck. Using 7 healthy subjects as controls, the depression in both monocyte chemotactic activity and monocyte random migration in the patients with tumors was found to be statistically significant by the "leading front" technique (P < 0.05). PMID- 8217133 TI - An animal model for hearing disturbance due to inner ear ischemia: photochemically induced thrombotic occlusion of the rat anterior inferior cerebellar artery. AB - A photochemical reaction between intravenous rose bengal and xenon light was used to induce a selective thrombus in the rat anterior inferior cerebellar artery (AICA). Compound action potentials (CAPs) were recorded by electrocochleography and cochlear blood flow (CBF) was monitored by laser Doppler flowmetry. Photothrombotic occlusion of the AICA caused inner ear ischemia to various degrees with or without alterations of the CAP. With use of this model we investigated the critical range of the CBF for preserving cochlear function, represented by the CAPs induced with 8 kHz half-wave of sinusoid at 100 dB SPL. Results then showed that a CBF range between 26.7% and 42.9% of baseline was somewhat critical for maintenance of cochlear function in an acute phase of ischemia. Pretreatment with heparin significantly delayed thrombotic occlusion of the AICA in a dose-dependent manner. Further use of our model for inner ear ischemia may be useful for studying pathophysiology and pharmacological therapy of cochlear disturbances subsequent to circulatory disorders. PMID- 8217134 TI - Differences in size and shape between the right and left sigmoid sinuses. AB - Whether or not the shape and size of the sigmoid sinus are affected by middle ear inflammation is still controversial. Using high-resolution computed tomography (CT), we examined the shape and cross-sectional area of the sigmoid sinus in 80 patients with unilateral chronic otitis media. Forty patients had right otitis media, and the others left otitis media. Whether chronic inflammation involved the right or left ear, a protrusive type of sigmoid sinus was found more frequently on the right than the left, while the cross-sectional area was significantly greater on the right. These findings suggest that a side difference affecting the sigmoid sinus would thus appear not to be caused by postnatal otitis media, but to originate in fetal life. The shape of the sigmoid sinus greatly varies among individuals and according to whether it is on the right or the left. Findings also indicate that a temporal bone CT is desirable to optimize surgical safety. PMID- 8217135 TI - Is an isthmus block a prerequisite for the development of an attic retraction cholesteatoma? AB - Computed tomography (CT) was used to investigate whether an isthmus block was present in 57 cases with attic retraction cholesteatomas. A ventilation route between the mesotympanum and attic was considered to exist in 30% of the cases and occurred predominantly in those ears with a cholesteatoma that did not extend into the antrum. Four cases were also found to have this ventilation route in CT scans taken before and after the development of cholesteatoma. These findings suggest that an isthmus block is not a prerequisite for the development of an attic retraction cholesteatoma. PMID- 8217136 TI - Adult rhabdomyoma extending from the nasopharynx to the skull base. AB - Adult rhabdomyoma is an exceedingly uncommon tumor in the head and neck. We present a case localized to the left parapharyngeal area in a 57-year-old woman. The various diagnostic measures used are discussed. Surgical removal is the treatment of choice. PMID- 8217137 TI - Detection of cancer recurrence in irradiated mandible using positron emission tomography. AB - Positron emission tomography (PET) is a promising method for pretherapeutic assessment of spread of squamous cell carcinomas (SCC) in the head and neck. A 41 year-old man with a history of operated and irradiated SCC of the tongue presented 4 years later with symptoms and signs of mandibular osteoradionecrosis. No changes related to malignancy could be seen in panoramic radiographs or computed tomography scanning with contrast enhancement. Since a biopsy of the involved region was positive for SCC, a PET study with [18F]fluorodeoxyglucose (FDG) was performed. In dynamic PET images, intensive uptake of FDG was seen in a small area close to the right mental foramen. A hemimandibulectomy with reconstruction using a free vascularized graft from iliac crest was performed. In the resected specimen, histological examination showed a 1.2-mm focus of SCC in the soft tissue and bone around the mental foramen. These findings indicate that FDG-PET might be useful for presurgical evaluation of cancer recurrence in a previously irradiated mandible, especially if PET can accurately differentiate viable tumor tissue from radiation-induced fibrosis and inflammation. PMID- 8217138 TI - A simplified vacuum blotting method for genomic sequencing and in vivo footprinting. PMID- 8217139 TI - Artifactual frame-shift p53 mutation at codon 249 detected with the Cyclist DNA sequencing method. PMID- 8217140 TI - Elimination of glycerol artifacts in cycle sequencing. PMID- 8217141 TI - A simplified protocol for isolation and characterization of ssM13 DNA templates for use in dideoxy sequencing. PMID- 8217142 TI - PCR-direct sequencing of a GC-rich region by inclusion of 10% DMSO: application to mouse c-jun. PMID- 8217143 TI - Preparation of template for automated sequencing using QIAGEN resin. PMID- 8217144 TI - Fast and economical large-scale preparation of high-quality plasmid DNA. PMID- 8217145 TI - Direct sequencing of double-stranded PCR products isolated from conventional agarose gels. PMID- 8217146 TI - A simple technique for pouring sequencing gels. PMID- 8217147 TI - Novel use of a polymeric chromophore in detecting sequence-specific DNA-binding proteins. PMID- 8217148 TI - Enhancement of ethidium bromide fluorescence in double-stranded DNA reacted with chloroacetaldehyde. PMID- 8217149 TI - Enhanced single-strand conformation polymorphism (SSCP) detection of point mutations utilizing methylmercury hydroxide. PMID- 8217150 TI - Simple and reliable determination of radioactive precursors incorporation into nucleic acids in vitro. PMID- 8217151 TI - An improved washing apparatus for nucleoside phosphorylation assays. PMID- 8217152 TI - Detection of parvovirus B19 DNA in amniotic fluid by PCR DNA amplification. PMID- 8217153 TI - High-throughput purification of M13 templates for DNA sequencing. AB - Two variants of methods for high-throughput preparation of single-stranded M13 DNA are described. Both variants are derived from previously described chemistry and are appropriate for purification of M13 templates in 96-deep well plates. In both variants, phenol extraction is replaced by treatment with sodium iodide to disrupt phage proteins prior to ethanol precipitation of M13 DNA. In one of the variants, nonderivatized paramagnetic particles are employed to collect aggregated M13 phage particles and DNA, thereby replacing the need for centrifugation. The other variant omits the magnetic particles and utilizes a centrifuge that can accommodate the 96-deep well plates. Although the purification scheme that uses magnetic separation results in a decreased yield of M13 DNA, it is amenable to robotic automation strategies and thus will be useful for genomic sequencing projects. Performed manually, either method can easily produce 192 templates in a few hours. Although both variants produce DNA of sufficient quantity for automated fluorescent DNA sequencing, the procedure that utilizes magnetic separation provides template DNA of higher quality. PMID- 8217154 TI - Rapid sequencing of viral DNA from filamentous bacteriophage. AB - Several techniques have been combined to facilitate rapid sequencing of filamentous phage DNA. Up to 768 clones can be processed with excellent results in one week by a single worker. PMID- 8217155 TI - Rapid isolation of DNA from fossil and museum specimens suitable for PCR. AB - We describe a simple process for extraction of DNA from amber-entombed fossils and museum specimens that is suitable for enzymatic amplification by PCR. Five to ten milligrams of the macerated specimen were mixed in 300 microliters of silica matrix and shaken at 55 degrees C for 1 h in a sterile, screw-capped microcentrifuge tube. After incubation, the silica matrix was transferred to the upper chamber of a SpinFilter, centrifuged at maximum speed for 1 min and then washed twice with 500 microliters of wash solution and the DNA eluted with 50 microliters of TE buffer. The eluate was used as template for PCR, and the results were evaluated by electrophoresis and nucleotide sequence analysis. All samples tested yielded positive results, which were subsequently verified by sequence analysis. It appears, at least in our hands, that the procedure described here is a rapid and efficient way of obtaining small amounts of DNA for PCR in museum and fossilized specimens. PMID- 8217156 TI - Microwave miniprep of total genomic DNA from fungi, plants, protists and animals for PCR. AB - A rapid procedure for the isolation of total DNA from various eukaryotic organisms is described. This method uses a common microwave oven for the alteration of cellular walls and membranes. The procedure is rapid and can be completed in as little as 15 minutes. The method has been used to isolate DNA from reptiles, plants, slime molds and other protists, and this DNA has been used for successful amplification of ribosomal genes from these organisms. The procedure is a time-saving and cost-effective process that helps to eliminate several sources of contamination that can be found in other DNA isolation procedures. PMID- 8217157 TI - A simple two-step method for efficient blunt-end ligation of DNA fragments. AB - The formation of recombinant plasmids results from ligation between one end of the linearized vector and one end of the insert (favored by high DNA concentration), followed by self-ligation of the newly created hybrid molecule (favored by low DNA concentration). Standard protocols recommend an average DNA concentration at which both events may occur. Since this DNA concentration is not optimum for both ligation events, efficient blunt-end ligation is compromised. We describe a method for blunt-end ligation starting at a high DNA concentration for 1 h then at 1/20 the initial DNA concentration overnight. The number of recombinant plasmids obtained with this method is about 10-fold higher than with standard protocols. Restriction digestion and agarose gel electrophoresis of 10 recombinant plasmids obtained with the two-step ligation method showed that all plasmids contained one copy of the insert. PMID- 8217158 TI - Transformation of Chlamydomonas reinhardtii with silicon carbide whiskers. AB - Nuclear transformation of intact (walled) cells of the green alga Chlamydomonas reinhardtii was achieved by agitating the cells in the presence of plasmid DNA and silicon carbide (SiC) whiskers. The protocol was used to introduce the wild type nitrate reductase structural gene into the nitrate reductase-deficient mutant strain nit1-305. Using SiC whiskers, 10-100 transformants per 10(7) cells were routinely produced, which is comparable to transformation rates achieved by agitating the cells with glass beads. In contrast to the glass bead protocol, cell viability was very high following treatment with SiC, with greater than 80% cell survival after agitation for 10 min. Agitation with SiC whiskers appears to be an efficient method for introducing DNA into intact C. reinhardtii cells and may prove to be applicable to other algal species for which cell wall mutants or protoplasting procedures are unavailable. PMID- 8217159 TI - Optimization of coupled PCR amplification and cycle sequencing of cloned and genomic DNA. AB - We describe optimization of a coupled amplification and cycle sequencing (CAS) method for rapid characterization of cloned or genomic DNA. Our modification of this method, termed coupled PCR amplification and cycle sequencing (CPACS), utilizes commercially available reagents, does not require template purification and produces high-quality sequence ladders from nanogram quantities of complex genomic DNA. The reactions have been streamlined to permit automation. Finally, we show that the technique can be applied more efficiently in conjunction with the AutoTrans 350 Direct Transfer Electrophoresis System and 33P-labeled sequencing primers. PMID- 8217160 TI - Formation of tight monolayers of guinea pig airway epithelial cells cultured in an air-interface: bioelectric properties. AB - In this study, we have developed an air-interface culture system in which guinea pig tracheobronchial epithelial (GPTE) cells rapidly form tight monolayers. Enzymatically isolated GPTE cells were plated on collagen-treated polycarbonate microporous cell culture inserts at a density of 10(6) cells/cm2 (day 0). Bioelectric properties of cultures grown in an air-interface were compared with those covered by medium. On day 1 for air-interface cultures, apical fluid was removed and basolateral fluid was replenished. For cultures covered by medium, varying volumes of apical fluid were used. On days 4 and 5 after plating, confluent GPTE monolayers in either liquid-covered or air-interface cultures exhibited similar monolayer resistance values > or = 1.0 kohm-cm2. However, the equivalent short-circuit current (Ieq) was significantly higher in air-interface cultures than those covered with medium on days 4 and 5. The Ieq in air-interface cultures on day 4 was 12.9 microA/cm2. These confluent GPTE cell monolayers cultured in air-interface could be a useful tool for studies of changes in bioelectric and ion transport properties in response to injury and mediators of inflammation. PMID- 8217161 TI - A novel expression system for Gs-coupled receptors. AB - Renal epithelial cells LLC-PK1 secrete high amounts of urokinase-type plasminogen activator (uPA) when stimulated through the cAMP-signaling pathway. Here we show that this characteristic can be used to identify rapidly LLC-PK1-derived cell lines expressing heterologous receptors that couple to Gs-proteins. A genomic clone encoding the mouse beta 2 adrenergic receptor (beta 2AR) was transfected stably into LLC-PK1 cells. Drug-resistant colonies were subsequently stimulated with isoproterenol and screened for the secretion uPA activity. Positive clones displayed dose-dependent uPA activity in response to isoproterenol, specifically bound the beta 2AR-agonist iodocyanopindolol and expressed beta 2AR-mRNA. The functional coupling of beta 2AR expression to the inducible uPA gene establishes that LLC-PK1 cells can be used to assay for beta 2AR (and beta 2AR-agonist) function. Our data suggest that this system can be used for functional expression of other heterologous receptors that couple to Gs-proteins. PMID- 8217162 TI - Chemiluminescent DNA sequencing with multiplex labeling. AB - Chemiluminescent detection techniques provide a sensitive, nonradioactive method for DNA sequencing. Standard Sanger dideoxy DNA sequencing reactions are initiated with biotinylated primers, separated by gel electrophoresis, transferred to nylon membrane and detected utilizing chemiluminescent 1,2 dioxetane substrates for alkaline phosphatase. A multiplex-labeling method was developed to permit detection of several overlapping sets of DNA sequence information on a single membrane, thereby increasing the productivity of a single gel electrophoretic separation. Primers labeled with different haptens at the 5' end were used to perform separate sequencing reactions. These were mixed together prior to electrophoresis, and the individual sequencing products sequentially detected using hapten-specific reagents. We incorporated primers labeled with biotin, digoxigenin, 2,4-dinitrophenyl or fluorescein, each consecutively detected with a hapten-specific alkaline phosphatase conjugate and CSPD 1,2 dioxetane chemiluminescent substrate. To further increase the amount of DNA sequence data that can be obtained from a single membrane, a direct transfer electrophoresis apparatus was used for simultaneous separation of the DNA sequencing reactions and membrane transfer. The resulting increased separation of the high molecular weight fragments yields 350-450 bp of readable DNA sequence data from each template. Chemiluminescent detection of overlapping sets of DNA sequencing reactions utilizing multiplex labeling, combined with direct transfer electrophoresis, provides an efficient, nonradioactive method for DNA sequencing. PMID- 8217163 TI - Enzymatic addition of fluorescein- or biotin-riboUTP to oligonucleotides results in primers suitable for DNA sequencing and PCR. AB - An enzymatic, post-synthetic, non-isotopic modification of oligonucleotides giving primers that are substrates for chain elongation by DNA polymerases is described. It is shown that terminal deoxynucleotidyl transferase incorporates preferentially and almost exclusively a single fluorescein- or biotin-riboUTP at the 3' terminus of oligonucleotides. This one-step procedure, using readily available materials, permits an economical enzymatic labeling of oligonucleotides designed for fluorescence-based or solid-state DNA sequencing or PCR and offers a convenient alternative to chemical modification. PMID- 8217164 TI - PCR-assisted large insertion/deletion mutagenesis. AB - A mutagenesis protocol is presented that allows the exchange or simultaneous insertion/deletion (INDEL) of large fragments of DNA. The technique uses long single-stranded DNA molecules synthesized by asymmetric PCR. Insertion of large DNA fragments (> 300 bp) was accomplished using these single-stranded DNAs without the need for restriction sites or for subcloning. We have used the method to exchange large DNA fragments in the study of DNA regulatory regions and protein domain function. PMID- 8217165 TI - Directional cloning of blunt-ended PCR products. AB - A method that allows the directional cloning of blunt-ended polymerase chain reaction (PCR) fragments is described. One PCR primer must be 5' phosphorylated. Extra bases are not required on either PCR primer. A linearized vector is enzymatically processed to contain a single 5'-terminal phosphate. The monophosphorylated vector is amenable to recombinant-insertion during ligation when the fragment is in the correct orientation. Increased recombinant yield results from incubating the monophosphorylated vector with a restriction enzyme (SrfI) that relinearizes nonrecombinant plasmids during the ligation reaction. PMID- 8217166 TI - 33P is preferable to 35S for labeling probes used in in situ hybridization. AB - We compared RNA probes labeled with 35S-UTP and 33P-UTP for use in in situ hybridizations. 33P-UTP was readily incorporated into in vitro transcribed RNA, producing 33P-labeled riboprobes of high specific activity. When the 33P- and 35S labeled riboprobes were compared in in situ hybridizations using two different tissues, we found that the 33P-labeled riboprobes were less "sticky" than the 35S labeled riboprobes, giving significantly less nonspecific background hybridization. Because of the low level of background stickiness, it was possible to use ten times more 33P-labeled riboprobe than 35S-labeled riboprobe without appreciably increasing background hybridization. Our findings indicate that, in most cases, 33P is the isotope of choice when labeling probes for in situ hybridizations. PMID- 8217167 TI - Rapid cycle sequencing in an air thermal cycler. AB - Cycle sequencing using Taq DNA polymerase has gained popularity recently due to reduced template requirements, improved signal and its ability to directly sequence PCR fragments. A major drawback to the technique is the time required for performing reactions in a block-based thermal cycler. To help cycle sequencing compete with other methods, we have modified the protocol to be performed in capillaries using an air-based thermal cycling instrument. This instrument has been developed and optimized for rapid, specific amplification of DNA by PCR. The resulting cycle sequencing methodology is faster than block-based approaches; a reaction can be completed in 25 min, compared with about 2 h in a conventional instrument. Thus, the speed of the technique is competitive with standard uncycled T7 or Taq reactions. Accuracy of the sequencing data is improved; two problem areas in the sequence obtained with a block cycler are ameliorated by the capillary methodology. This technique represents a novel approach to cycle sequencing that will further the development of capillary-based analytical methods. PMID- 8217168 TI - Quantitative detection of single-copy genes in nanogram samples of human genomic DNA. AB - We have developed methods for Southern hybridization analysis of single-copy genes in as little as 10 ng of mammalian DNA electrophoresed under either neutral or alkaline conditions. The signal on the radiogram is proportional to the quantity of DNA. These methods permit Southern hybridization analysis of DNA from about 2 x 10(3) cultured human cells. The use of minimal cell numbers greatly reduces the costs of culturing cells for hybridization analysis and makes feasible analysis of DNA from tissues or cell types available only in limited quantities. PMID- 8217169 TI - Automation of large-scale HLA oligotyping using a robotic workstation. AB - The ability to amplify specific genomic segments by the PCR has made the analysis of DNA polymorphism with oligonucleotidic probes a practical approach to HLA class II typing. However, to make this method more accurate and applicable to large-scale typing, technical and logistic limitations must be overcome and the risk of human errors must be reduced. To address this problem, we developed an automated procedure, using the Biomek 1000. The system consists of a workstation with a robotic arm and an instrument tablet, an electronic interface unit and an IBM PC. It was modified by the addition of a dot-blot apparatus. Automatic preparation of 96 samples for simultaneous DNA amplification is possible, together with PCR product dilution, distribution and dot-blotting. The robot prevents sample contamination, eliminates human errors and reduces operating costs by decreasing the working time by 50%. Thus, the system is suitable for routine analysis, and it also improves typing accuracy. Furthermore, this system can be adapted for a variety of new DNA-typing strategies that require an initial DNA amplification step. PMID- 8217170 TI - An American clinician in Archie Brain's court. PMID- 8217171 TI - The laryngeal mask airway: anesthetic gas leakage and fiberoptic control of positioning. AB - STUDY OBJECTIVE: To examine the anesthetic gas leakage and prelaryngeal position of the laryngeal mask airway (LMA). DESIGN: Clinical trial evaluating LMA ventilation conditions. SETTING: Lithotripsy room of a urology clinic at a university hospital. PATIENTS: 100 adult ASA physical status I and II patients undergoing general anesthesia for kidney stone lithotripsy. INTERVENTIONS: Anesthesia was induced with propofol 1.5 to 2.5 mg/kg intravenously (IV) and fentanyl 1 to 1.5 micrograms/kg IV and maintained with isoflurane plus nitrous oxide in oxygen. MEASUREMENTS AND MAIN RESULTS: Waste anesthetic gas concentration, an indicator of mask tightness during intermittent positive pressure ventilation, was measured using an infrared oxide analyzer. LMA position in relation to laryngeal skeleton was assessed using fiberoptic laryngoscopy. The LMA was found to be gastight in 62% of patients, with a peak airway pressure up to 25 cmH2O. During peak airway pressure ventilation less than 10 cmH2O and during spontaneous ventilation, waste anesthetic gas contamination in the anesthesiologist's breathing zone was within legal limits in every case. During peak airway pressure ventilation up to 30 cmH2O, contamination was found within legal limits in 78% of all cases. Fiberoptic control showed a central position in 59% of cases, lateral deviations to the left or right in 29%, dorsal positions in 8%, and ventral positions in 4%. Incorrect ventral or dorsal positioning was related to forced reclining or forced flexion of the patient's head. There was no correlation between LMA position and tightness. The esophageal entrance was visible in 15 patients using high peak airway pressure greater than 25 cmH2O. CONCLUSIONS: The LMA is a new airway management technique with good qualities of tightness and ventilation conditions. However, contraindications such as patients with a full stomach, intra-abdominal surgery, high peak airway pressure, prolonged operation, and an inexperienced anesthesiologist apply. PMID- 8217172 TI - Recovery room risk and outcome associated with renal extracorporeal shock wave lithotripsy. AB - STUDY OBJECTIVES: To determine (1) the general risk and outcome in the recovery room among 4 different anesthetic techniques associated with 2 different extracorporeal shock wave lithotripsy (ESWL) machines and (2) any gender-related differences among patients undergoing ESWL. DESIGN: Retrospective statistical analysis. SETTING: University medical center. PATIENTS: 2,203 ASA physical status I-IV patients undergoing ESWL over a 46-month period. INTERVENTIONS: A review of the chart records of patients who received 1 of 4 anesthetic techniques (general, spinal, epidural, or monitored anesthesia care) on 1 of 2 ESWL machines. MEASUREMENTS AND MAIN RESULTS: A positive finding was defined as a complication and/or side effect of such significance as to require a treatment order or recovery room note on the patient's chart. The main complications and/or side effects were nausea and/or vomiting, flank pain, and hypertension. Female patients experienced flank pain and nausea and/or vomiting with general anesthesia and monitored anesthesia care at approximately twice the frequency of males. CONCLUSIONS: (1) Overall, ESWL is relatively safe. Both machine types and all anesthetic techniques exhibited a low risk and good outcome. (2) There appear to be gender-related differences during ESWL. Female and male patients may have different pain and nausea and/or vomiting thresholds during ESWL. PMID- 8217173 TI - Bronchial mucus transport in chronic smokers and nonsmokers during general anesthesia. AB - STUDY OBJECTIVE: To compare bronchial mucus transport velocity in smokers and nonsmokers. DESIGN: Prospective consecutive-sample trial. SETTING: University hospital. PATIENTS: 12 smokers and 22 nonsmokers undergoing major abdominal or thoracic surgery with postoperative mechanical ventilation. INTERVENTIONS: After the end of the operation, bronchial mucus transport velocity was measured with a small volume (0.05 to 0.08 ml) of technetium 99-m labeled albumin microspheres with an activity of 1.5 MBq. The radiolabeled bolus was deposited on the dorsal mucosal surface at the distal end of the right and left main bronchus via flexible bronchoscopy. The movement of the microspheres toward the trachea was visualized and recorded using a scintillation camera. Quantitative evaluation was based on the path-time diagram. After determination of bronchial mucus transport velocity, patients were examined daily over 4 days to record pulmonary complications (retention of secretion and nosocomial pneumonia). MEASUREMENTS AND MAIN RESULTS: Smokers were comparable to nonsmokers with respect to age, preoperative lung function tests, body temperature, duration of mechanical ventilation, dose of anesthetics, and intraoperative blood loss. Smokers had a significantly slower bronchial mucus transport velocity compared with nonsmokers: in the left bronchus, 1.3 mm/min (0 to 9.6 mm/min) (median with range) versus 9.7 mm/min (3.7 to 15.3 mm/min) (p < 0.001); in the right bronchus, 2.5 mm/min (0 to 16.0 mm/min) versus 8.3 mm/min (5.5 to 15.3 mm/min) (p < 0.01). Pulmonary complications occurred in 4 smokers and 1 nonsmoker. CONCLUSIONS: When measured during general anesthesia, smokers have a slower bronchial mucus transport than nonsmokers. This may be related to postoperative pulmonary complications in smokers. PMID- 8217174 TI - The effect of intravenous dextrose infusion on postbypass hyperglycemia in pediatric patients undergoing cardiac operations. AB - STUDY OBJECTIVE: To determine whether elimination of intraoperative dextrose containing infusions affects post-cardiopulmonary bypass hyperglycemia in pediatric patients. DESIGN: Randomized, unblinded, saline-controlled study of perioperative glucose infusions in children undergoing cardiac surgery. SETTING: Cardiac surgery suite and pediatric intensive care unit (ICU) of a university medical center. PATIENTS: 33 consecutive, nondiabetic children undergoing cardiac surgery with deep hypothermia over an 8-month period. INTERVENTIONS: Group A (n = 16) received only normal saline infusions intraoperatively, and Group B (n = 17) received 5% dextrose and lactated Ringer's solution exclusively. Blood glucose was sampled immediately after induction of anesthesia, prior to cardiopulmonary bypass (CPB), after separation from CPB, on arrival in the ICU, and the morning of the first postoperative day. Data were analyzed using Student's t-test for independent samples, paired t-test, and analysis of variance, with p < 0.05 considered significant. MEASUREMENTS AND MAIN RESULTS: Although moderate elevations in blood glucose (mean less than 165 mg/dl) after CPB were present in Group A, significantly higher levels (mean greater than 250 mg/dl) were noted in Group B. No children were hypoglycemic (glucose less than 40 mg/dl). Glucose levels were normal in both groups on the morning of the first postoperative day despite patients' having received continuous dextrose infusions in the ICU and the presumed stress of emergence from anesthesia. CONCLUSIONS: Extreme postbypass hyperglycemia can be controlled by eliminating intraoperative dextrose infusions. Hypoglycemia, an unlikely event, can easily be avoided by regular blood sampling, which is facilitated by the routine placement of arterial catheters. PMID- 8217176 TI - The effect of ondansetron on atracurium-induced neuromuscular blockade. AB - STUDY OBJECTIVE: To determine whether treatment with ondansetron, a new antiemetic drug, affects nondepolarizing neuromuscular blockade. DESIGN: Randomized, double-blind, prospective study. SETTING: Operating room at a university medical center. PATIENTS: 30 ASA physical status I and II patients scheduled for elective surgery. INTERVENTIONS: After the induction of anesthesia with midazolam 2 to 4 mg/kg, sodium thiopental 6 to 8 mg/kg, and fentanyl 4 to 8 micrograms/kg, the ulnar nerve was stimulated at the wrist through subcutaneous needle electrodes at a frequency of 0.15 Hz. The response to stimulation was measured and recorded with a force-displacement transducer applied to the thumb. Patients were randomized to one of three treatment groups. A steady baseline to ulnar nerve stimulation with nitrous oxide-oxygen-opioid-thiopental anesthesia was established. The first study group (Group 1) received a placebo, the second group (Group 2) received 8 mg of ondansetron, and the third group (Group 3) received 16 mg of ondansetron as an intravenous infusion over 5 minutes. Patients were then given incremental doses of atracurium 0.05 mg/kg at 3-minute intervals to establish approximately 95% twitch inhibition so as to construct a dose response curve. An atracurium infusion was then begun to maintain a constant degree of neuromuscular blockade. At the end of surgery, patients were allowed to recover spontaneously, or pharmacologic antagonism of residual neuromuscular blockade was achieved with neostigmine 0.05 mg/kg and glycopyrrolate 0.01 mg/kg. Mechanomyographic response to train-of-four stimuli (2 Hz for 2 seconds) every 20 seconds was monitored during the atracurium infusion and recovery from neuromuscular blockade. MEASUREMENTS AND MAIN RESULTS: Log dose-response curves were determined for the study groups and compared using analysis of variance (ANOVA). The 50%, 75%, and 95% effective doses (ED50, ED75, and ED95) were calculated from the equation describing the log dose-response. Maintenance infusion rates were determined, and the neostigmine-accelerated recovery index of 25% to 75% was measured for each group. The results were compared using ANOVA. There were no significant differences among the treatment groups with respect to maintenance infusion rate (7.8 +/- 1.8 micrograms/kg/min for Group 1, 7.7 +/- 2.5 micrograms/kg/min for Group 2, and 7.3 +/- 2.3 micrograms/kg/min for Group 3) or neostigmine-accelerated recovery interval of 25% to 75% (4.5 +/- 2.3 minutes, 4.4 +/- 3.1 minutes, 6.6 +/- 3.9 minutes in Groups 1, 2, and 3, respectively). The log dose-response data for Groups 1, 2, and 3 did not differ significantly (p = 0.068), and the calculated ED95 in each treatment group demonstrated no dose related change (0.254 +/- 0.022, 0.279 +/- 0.033, and 0.240 +/- 0.022 for Groups 1, 2, and 3, respectively). CONCLUSIONS: Ondansetron is an antiemetic drug that can be used in the perioperative period without concern for potentiation of nondepolarizing neuromuscular blockade, change in atracurium maintenance dose, or change in rate of neostigmine-induced recovery from neuromuscular blockade with atracurium. PMID- 8217175 TI - Loss of somatosensory evoked potentials during intramedullary spinal cord surgery predicts postoperative neurologic deficits in motor function [corrected]. AB - STUDY OBJECTIVES: To estimate the sensitivity and specificity of somatosensory evoked potentials (SSEPs) for predicting new postoperative motor neurologic deficits during intramedullary spinal cord surgery; to establish whether SSEPs more accurately predicted postoperative deficits in position and vibration sense than in strength. DESIGN: Prospective open and retrospective study. SETTING: University-affiliated hospital. PATIENTS: 20 patients with intramedullary spinal cord tumors scheduled for surgery with intraoperative SSEPs. INTERVENTIONS: Median, ulnar, and tibial nerve cortical and subcortical SSEPs were recorded continuously. MEASUREMENTS AND MAIN RESULTS: Conventional intraoperative SSEP criteria considered indicative of neurologic injury were modified and defined as either the complete and permanent loss of the SSEP or the simultaneous amplitude reduction of 50% or greater in the nearest recording electrode rostral to the surgical site and 0.5 millisecond increase in the central latency. Our definition required confirmation of both amplitude and latency changes on a repeated average. All patients had 1 or more SSEPs, which were reproducible and sufficiently stable for analysis throughout the operation. Six patients developed new postoperative neurologic deficits. One had new motor deficits in an extremity from which no baseline SSEPs could be elicited. In each of the other 5 patients, significant SSEP changes preceded the postoperative motor deficits in the extremity or extremities monitored. In no patient without a new postoperative motor deficit was there a significant change in the SSEP. In only 2 of these 5 patients was there a documented postoperative loss or diminution in vibration or position sense. CONCLUSIONS: Intraoperative SSEP changes during intramedullary spinal cord surgery are a sensitive predictor of new postoperative motor deficits, but such changes may not correlate reliably with postoperative deficits in position or vibration sense. In this setting SSEP monitoring serves primarily to reassure the operating team that, when the SSEPs remain constant, the surgery has not caused additional injury. PMID- 8217177 TI - Does the use of methylmethacrylate cement in total shoulder replacement induce hemodynamic or pulmonary instability? AB - STUDY OBJECTIVE: To investigate whether the use of methylmethacrylate cement causes hemodynamic or pulmonary instability during total shoulder replacement surgery. DESIGN: Prospective, nonrandomized study. SETTING: Operating room. PATIENTS: 9 ASA physical status I and II patients. INTERVENTIONS: A 20-gauge radial artery catheter was placed in the wrist opposite the surgical site. Sedation with midazolam was provided, and a pulmonary artery catheter was placed through an 8.5-Fr introducer into the patient's right internal jugular vein. MEASUREMENTS AND MAIN RESULTS: Before induction of anesthesia, systolic, diastolic, and mean arterial blood pressures; heart rate; central venous pressure; systolic, diastolic, and mean pulmonary artery pressures; pulmonary capillary wedge pressure; and thermodilution cardiac output measurements were obtained. Arterial and mixed venous blood gas samples also were collected and analyzed for calculation of Qs/Qt. These hemodynamic and pulmonary parameters were measured again just before cementing of each prosthesis with methylmethacrylate cement and at 1, 5, 10, and 20 minutes after cementing. There were no statistically significant changes in any of the measured hemodynamic parameters at any time. There was no statistically significant difference in the calculated intrapulmonary shunt fraction. CONCLUSION: In this study population, the use of methylmethacrylate for total shoulder replacement was not associated with adverse hemodynamic events or increased intrapulmonary shunting. PMID- 8217178 TI - Effect of phenylephrine bolus administration on left ventricular function during postural hypotension in anesthetized patients. AB - STUDY OBJECTIVE: To investigate the effect of intravenous (IV) phenylephrine (PHE) bolus administration on left ventricular function in patients who developed postural hypotension during isoflurane anesthesia in the head-up tilt (reverse Trendelenburg) position. DESIGN: Prospective "before-after" trial. SETTING: Operation theater of a university medical center. PATIENTS: 15 ASA physical status I and II patients without cardiovascular disorders. INTERVENTIONS: The anesthetized patients were tilted from a supine horizontal to a 30-degree reverse Trendelenburg position. Once a steady state was achieved, PHE 3 micrograms/kg was administered as an IV bolus dose. MEASUREMENTS AND MAIN RESULTS: Transesophageal echocardiography was used to assess left ventricular function. We measured blood pressure (BP); heart rate; left ventricular end-systolic and end-diastolic area, diameter, and wall thickness; and ejection time at baseline and after tilt, immediately before and for a period of 3 minutes after PHE injection. We calculated fractional area change (FAC), mean velocity of circumferential fiber shortening (mVcf), and end-systolic wall stress. Head-up tilt caused a reduction of mean arterial pressure [from 68 to 54 mmHg (mean)], end-systolic and end diastolic left ventricular area (from 9.7 to 6.5 cm2 and from 19.2 to 13.1 cm2, respectively) and end-systolic wall stress (from 56 to 33 10(3).dyne/cm2). FAC and mVcf remained unaltered. PHE administration restored baseline values or overcompensated the changes caused by tilt. FAC slightly decreased in response to PHE (from 0.51 to 0.43), end-systolic wall stress increased to 83 10(3).dyne/cm2, and mVcf remained unchanged. CONCLUSION: PHE bolus administration effectively restored BP and cardiac filling, which were reduced after head-up tilt, without causing a relevant impairment of left ventricular function or an increase in end systolic wall stress above the upper normal limit. PMID- 8217179 TI - Midazolam pretreatment does not ameliorate myoglobinemia or the clinical side effects of succinylcholine. AB - STUDY OBJECTIVE: To determine whether the levels of serum myoglobin and the occurrence of fasciculations and postoperative symptoms following a single dose of succinylcholine are modified by the prior administration of midazolam. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Outpatient surgical service of a university hospital. PATIENTS: 69 ASA physical status I and II healthy, adult female outpatients undergoing laparoscopy (for diagnosis or tubal ligation) with general anesthesia that included succinylcholine. INTERVENTIONS: Patients received pretreatment of either a saline placebo (Group 1, n = 31) or intravenous midazolam 0.03 mg/kg (Group 2, n = 38) 5 minutes before succinylcholine. MEASUREMENTS AND MAIN RESULTS: Serum myoglobin prior to pretreatment and at 5 (t5) and 30 (t30) minutes after succinylcholine was determined by radioimmunoassay. Pain was assessed by telephone interview 24 to 36 hours postoperatively. Baseline myoglobin levels ranged from 14 to 69 ng/ml; the 5- and 30-minute samples varied widely (range, 16 to 900 ng/ml). The rise was 3 or more SDs above the baseline mean in 23% and 42% of Group 1 at t5 and t30, respectively, and in 21% and 35% of Group 2 at t5 and t30, respectively. The differences between groups were not significant. The frequency of fasciculations (77% in Group 1, 87% in Group 2), postoperative sore throat (64% in Group 1, 57% in Group 2), and myalgias (44% in Group 1, 51% in Group 2) also was not significantly different between groups. CONCLUSIONS: Midazolam had no effect on myoglobin level or postoperative symptoms following succinylcholine. PMID- 8217180 TI - Thromboelastography and Sonoclot analysis in the healthy parturient. AB - STUDY OBJECTIVE: To compare values for two whole blood viscoelastic coagulation tests, thromboelastography (TEG) and Sonoclot analysis (Sonoclot R Coagulation Analyzer, Sienco, Inc., Morrison, CO), between healthy parturients and nonparturients. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: 41 healthy, nonpregnant females and full-term nonlaboring and laboring parturients. INTERVENTIONS: Blood samples for TEG and Sonoclot analysis were taken from all patients. TEG tracings were analyzed for reaction time (R), coagulation time (RK), the difference between RK and R (K), clot formation rate (alpha degree), and maximum amplitude (MA) values. Sonoclot tracings were analyzed for onset, rate increases, peak, and rate decreases values. MEASUREMENTS AND MAIN RESULTS: All TEG values were significantly different between nonpregnant females and parturients (p < 0.05). Sonoclot analysis showed that the parturients had a significantly decreased onset and increased primary slope (rate increases) in comparison to the nonpregnant females (p < 0.05). CONCLUSION: The differences found in the parturients reflect a hypercoagulable state. If these tests are to be used in evaluating obstetric patients, the results should be compared with values obtained for healthy parturients, not healthy nonparturients. PMID- 8217181 TI - Mild core hyperthermia does not alter electroencephalographic responses during epidural-enflurane anesthesia in humans. AB - STUDY OBJECTIVES: To determine the electroencephalographic (EEG) changes induced by mild hyperthermia during enflurane anesthesia and to test the reliability of two new infrared thermometers. DESIGN: Prospective laboratory evaluation. SETTING: The Thermoregulation Research Laboratory at the University of California, San Francisco. VOLUNTEERS: 6 healthy female volunteers aged 30 +/- 8 years. INTERVENTIONS: Epidural anesthesia (approximately T10 dermatome) was induced and maintained using 2-chloroprocaine anesthesia. General anesthesia was induced by inhalation of nitrous oxide and enflurane and maintained with enflurane at an end-tidal concentration of 1.7%. A minimum of 2 degrees C core hyperthermia was induced by active cutaneous warming, and the volunteers subsequently were passively cooled. MEASUREMENTS AND MAIN RESULTS: EEG data were recorded from gold cup electrodes positioned at FP1 and FP2, with the reference electrode at CZ and the ground lead on the mastoid. In addition to routine EEG parameters, we evaluated the bispectral index. Bispectral analysis quantifies the phase coupling between various frequencies in the power spectrum and may be a useful measure of anesthetic depth. Core temperature was measured at the left tympanic membrane and distal esophagus. Core temperature also was determined from the right ear using two new, infrared tympanic membrane thermometers. One of these directly measures tympanic temperature, and the other extrapolates core temperature from the external ear canal. Induction of 2 degrees C core hyperthermia did not produce statistically significant or clinically important changes in beta or delta power, the 95% spectral edge frequency, or the bispectral index. Temperatures recorded from the right ear by the direct thermometer were 0.27 degrees C +/- 0.33 degrees C less than those measured in the left ear, but the values correlated well (r2 = 0.95 +/- 0.04). Temperatures recorded from the right ear by the core temperature extrapolater were 0.42 degrees C +/- 0.33 degrees C lower than those measured in the left ear, and the correlation between values was slightly worse (r2 = 0.83 +/- 0.16). CONCLUSIONS: Since mild core hyperthermia does not alter routine EEG parameters or the bispectral index, typical perianesthetic thermal disturbances are unlikely to obscure EEG estimates of anesthetic depth. Both the direct thermometer and the core temperature extrapolater were found to be sufficiently accurate and precise for routine clinical use, but the direct thermometer would be preferable in the perioperative period. PMID- 8217182 TI - The BAAM and endotrol endotracheal tube for blind oral intubation. Beck Airway Air Flow Monitor. AB - Blind oral intubation in a spontaneously breathing patient can be facilitated with a combination of two devices used mainly for nasotracheal intubation, the BAAM (Beck Airway Air Flow Monitor, Great Plains Ballistics, Lubbock, TX) and the Endotrol endotracheal tube (Mallinckrodt Critical Care, Inc., St. Louis, MO). We describe a case in which intubation of a spontaneously breathing intensive care unit patient was unsuccessful by traditional methods. In the successful approach we describe, the tube was passed through the oral cavity and pharynx in a blind fashion, using the BAAM's whistling sound for guidance and the plastic ring of the Endotrol tube to help positioning. This equipment combination may be useful in certain difficult intubation situations. PMID- 8217183 TI - Bilateral pneumothoraces from a malfunctioning resuscitation valve. AB - Disposable resuscitation valves appear as relatively simple devices used to ventilate patients during both emergent situations and transport from the operating room to the intensive care unit. We report a case of a nonfunctional disposable resuscitation valve that resulted in barotrauma and bilateral pneumothoraces. A routine check for proper function of these valves before use in critically ill patients may help to eliminate such cases. PMID- 8217184 TI - Hydromediastinum following insertion of a central venous pressure line via the right external jugular vein. AB - The insertion of a central venous pressure (CVP) catheter has been known to be associated with a variety of complications. Among these, isolated hydromediastinum is relatively rare. We recently encountered a patient who developed hydromediastinum due to extravascular penetration of a CVP line inserted via the right external jugular vein. The clinical manifestations and significance of this complication are discussed. PMID- 8217185 TI - An analysis of the factors leading to crossed gas lines causing profound hypercarbia during general anesthesia. AB - With increasing use of laparoscopic techniques to facilitate surgical procedures in closed cavities, our institution has installed piped-in carbon dioxide (CO2) in most of our operating rooms. This case report describes an occurrence of a nitrous oxide hose being connected to a CO2 outlet, resulting in profound hypercarbia. The factors, human and mechanical, leading to this error are discussed, as well as the process of diagnosis and the subsequent treatment. PMID- 8217186 TI - Reciprocal expression of pleiotrophin and midkine in normal versus malignant lung tissues. AB - Abundant evidence suggests that growth factors are important mediators of non small cell lung cancer (NSCLC) growth. Although multiple growth factors have been found to be produced by NSCLC tissues, little is known about possible differences in growth factor expression between malignant and adjacent normal lung tissues. Variation in growth factor expression between normal and malignant lung tissues could be potentially useful diagnostically and therapeutically. In studies reported here, the expression of the angiogenic growth factor pleiotrophin (PTN) and homolog midkine (MK) was assessed in resected normal and malignant lung tissues. Primers specific for the two growth factors were used to amplify reverse transcriptase-produced DNA copies of RNA transcripts harvested from the tissues. This analysis revealed that all normal lung tissues examined (n = 17) expressed PTN but only two expressed MK. Conversely, all of the resected lung cancers (n = 20) expressed MK but only one expressed PTN. These results demonstrated a striking reciprocal expression pattern of MK and PTN in normal versus malignant lung tissue. PMID- 8217187 TI - Mast cells are essential for the full development of silica-induced pulmonary inflammation: a study with mast cell-deficient mice. AB - Silicosis provides a good model for chronic interstitial pulmonary inflammation. In order to clarify the role of mast cells in the development of interstitial lung diseases, silica suspension was transnasally administered to mast cell deficient mice (WBB6F1-W/Wv) and their mast cell-intact littermates (WBB6F1( )+/+) as well as to normal mice (C57BL/6). Histologic examinations and analyses of bronchoalveolar lavage fluid (BALF) components indicated that silica instillation induces less severe lung lesions in mast cell-deficient mice than in mast cell-intact mice. BALF neutrophilia was prominent in mast cell-intact mice, but mast cell-deficient mice developed significantly milder BALF neutrophilia. An increase in the number of lung mast cells was observed in mast cell-intact mice. To further prove the involvement of mast cells, bone marrow-derived cultured mast cells from +/+ mice were adoptively transferred to mast cell-deficient mice. These mast cell-reconstituted mice developed more severe pulmonary lesions than did the mast cell-deficient mice; the severity of the lesions was similar to that in mast cell-intact mice. In addition, BALF neutrophilia was elicited by mast cell reconstitution. A significant number of mast cells was found in the lungs of mast cell-reconstituted mice when silica was administered. These results suggest the involvement of mast cells in the development of silicosis and implicate interactions between mast cells and neutrophils in the pathogenesis of this disorder. PMID- 8217188 TI - Migration of dendritic cells into the draining lymph nodes of the lung after intratracheal instillation. AB - The migration of dendritic cell (DC)-enriched populations and alveolar macrophage (AM) populations isolated from PVG RT7.2 rats was studied after local administration to recipient PVG RT7.1 rats. The monoclonal antibody His41, which is directed against the common leukocyte antigen of the RT7.2 rat, was used to detect migrated cells. Injection of the splenic DC and AM subcutaneously into the footpads resulted in migration of both cell types to the popliteal lymph nodes after 24 h. DC located predominantly in the T cell-dependent areas, whereas AM located more in the medulla and medullary cords and spread throughout the outer cortex area. After intratracheal instillation of splenic DC, these cells were found predominantly in T cell-dependent areas of the draining lymph nodes of the lung after 24 h. In contrast, AM did not migrate to the draining lymph nodes after intratracheal instillation. Combined with those from earlier studies, these data show that DC present in the alveolar lumen may pick up airborne antigen and migrate to the draining lymph nodes of the lung, where they can induce primary T cell responses. PMID- 8217189 TI - Interleukin-8-induced transcellular neutrophil migration is facilitated by endothelial and pulmonary epithelial cells. AB - Interleukin-8 (IL-8) is an 8,000 D protein produced by many cells and has potent neutrophil chemoattractant and activating properties. Indeed, there is substantial data supporting a role for IL-8 in neutrophilic lung inflammatory responses. In vivo, neutrophils must adhere to and then migrate across endothelial and epithelial cell barriers in order to reach inflammatory foci. Therefore, we examined IL-8-induced neutrophil migration through naked filters and through human umbilical vein endothelial (HUVE) cells and human pulmonary type II-like epithelial cells (A549) cultured on these filters. IL-8 induced both dose- and time-dependent migration of neutrophils across all three barriers. At IL-8 concentrations greater than 10(-8) M, neutrophil migration across both endothelial and epithelial cell barriers was significantly greater than that observed across naked filters. In addition, time-course experiments indicated that neutrophil migration continued to occur for up to 3 h across both cellular barriers while neutrophil migration across naked filters plateaued by approximately 60 to 90 min. Migration of neutrophils through all barriers was completely inhibited by anti-IL-8 neutralizing antibody. The increased migration observed through both cellular barriers was not due to either changes in chemotactic gradients or the production of other soluble chemotactic factors by IL-8-stimulated HUVE and A549 cells versus naked filters. Furthermore, pretreatment of monolayers with actinomycin-D had no effect on the degree of transcellular migration. Thus, the facilitation of neutrophil migration through HUVE and A549 monolayers is not dependent upon new protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217190 TI - Oxidative stress causes a protein kinase C-independent increase of paracellular permeability in an in vitro epithelial model. AB - To evaluate the response of an epithelial barrier to a moderate but sustained oxidative stress, we cultured monolayers of Madin Darby canine kidney cells on microporous filters and exposed them to the hypoxanthine-xanthine oxidase (HX-XO) reaction. The transepithelial permeability coefficient for mannitol (Pm) was assessed as a marker of paracellular permeability. When the oxidative stress was limited in intensity and duration (production of 10 nmol/ml/min O2- with generation of 467 +/- 30 nmol/ml H2O2 over 1 h), we observed an increase of Pm with a delay of several hours (324 +/- 65% of baseline by 6 h, P < 0.005). There was complete return to control values by 24 h. The increase of Pm did not appear to be related to a depletion of cellular ATP. Protein kinase C (PKC) activity did not increase, and the rise in Pm was not prevented by CGP 41,251, a specific inhibitor of PKC. By contrast, CGP 41,251 inhibited the Pm increase that was elicited by PDBU, a phorbol ester that activates PKC. In our model, we conclude that a reversible increase of paracellular permeability occurs after oxidative stress independently of ATP depletion or PKC activation. Other, as yet unknown mechanisms have to be involved in this process. PMID- 8217191 TI - Stimulation of the rat alveolar macrophage respiratory burst by extracellular adenine nucleotides. AB - Exogenous nucleotides can serve as extracellular factors that cause significant functional changes in numerous cells, including phagocytes. In the current study, addition of ATP, ADP, and ATP gamma S directly stimulated the respiratory burst (superoxide production) by rat alveolar macrophages, whereas adenosine and AMP did not. The relative potency of these nucleotides at saturating concentration was ADP > or = ATP gamma S >> ATP; however, simultaneous addition of maximally stimulatory concentrations of ADP and ATP (100 microM of each) produced an additive effect suggesting involvement of two P2 receptors. Following addition of the nucleotides, an elevation of intracellular Ca2+ ([Ca2+]i) occurred within seconds, followed by a decline within 1 min but with a prolonged elevation above baseline for at least 5 min. Removal of extracellular Ca2+ only slightly attenuated the initial elevation, indicating that adenine nucleotides stimulate the rapid release of intracellular Ca2+ stores. Removal of extracellular Ca2+ also eliminated the sustained elevation in [Ca2+]i and markedly suppressed the respiratory burst. Incubation with verapamil, a Ca2+ channel blocker, also significantly inhibited the respiratory burst stimulated by ATP. These studies demonstrate that adenine nucleotides stimulate a Ca(2+)-dependent respiratory burst by rat alveolar macrophages, probably through purinergic receptors. PMID- 8217192 TI - Expression and regulation of tumor necrosis factor in macrophages from cystic fibrosis patients. AB - Cachexia and anorexia commonly occur in patients with cystic fibrosis (CF), particularly those with severe pulmonary compromise and heavy tracheobronchial colonization with Pseudomonas aeruginosa. Current understanding of the pathophysiology of cachexia attributes much of the anorexia and weight loss to the effects of the cytokine tumor necrosis factor (TNF), which is secreted by endotoxin-stimulated macrophages. It has further been suggested that TNF may play a role in the pathobiochemistry of CF cachexia, secondary to the localized inflammatory response in the lung or wider systemic activation of cells of the monocyte-macrophage series in response to endotoxin. This study investigates TNF production and gene expression by peripheral blood monocyte-derived macrophages from CF patients, compared with normals (NL). The results indicate that although both cell populations responded dose-dependently to lipopolysaccharide (LPS); CF macrophages, upon stimulation with LPS at concentrations of 1 to 1,000 ng/ml, consistently produced substantially higher amounts of TNF than NL macrophages. At the molecular level, Northern blot analysis also revealed that both macrophage populations expressed TNF mRNA in response to LPS in a dose-dependent manner. However, at the same LPS concentrations, CF macrophage TNF mRNA expression was 2- to 4-fold greater than that of NL macrophages. LPS had no effect in either macrophage population on mRNA for CHO-B, a constitutive probe. To investigate differences between NL and CF macrophage TNF regulation, nuclear run-on/half-life studies as well as studies addressing potential differences in LPS membrane interactions and signal transduction were performed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217193 TI - Rat surfactant apoprotein A (SP-A) exhibits antioxidant effects on alveolar macrophages. AB - The effects of surfactant apoprotein A (SP-A) on the superoxide production of rat alveolar macrophages (AM) were studied. Superoxide production was measured by the ferricytochrome c reduction method. When AM were incubated with SP-A only during the measurement of superoxide production, superoxide production was not influenced by SP-A. However, when AM were preincubated with SP-A at a concentration of 1, 2, and 10 micrograms/ml, superoxide production by AM was significantly inhibited (P < 0.05, P < 0.01, P < 0.01, respectively). The superoxide production of AM stimulated by PMA was significantly inhibited by SP-A at a concentration of 1 microgram/ml (P < 0.01), and superoxide production stimulated by zymosan was also inhibited by SP-A at a concentration of 10 micrograms/ml (P < 0.05). Suppression of superoxide production of unstimulated and PMA-stimulated AM was significantly inhibited by anti-SP-A antibody. Superoxide generation by the xanthine and xanthine oxidase system was not affected by the presence of SP-A. Our results suggest that superoxide production of AM can be inhibited by SP-A and that this inhibitory effect on AM is due to a specific effect of SP-A. From these results, it is speculated that SP-A may have a protective role for oxidant injury by AM in the lung. PMID- 8217194 TI - Mitogen-inducible prostaglandin G/H synthase is expressed in canine mastocytoma cells. AB - A mitogen-inducible prostaglandin G/H synthase (PGHS-2 or cyclooxygenase-2) has recently been cloned from chicken and mouse fibroblasts. This protein is distinct from classic prostaglandin G/H synthase (PGHS-1 or cyclooxygenase-1) but has a similar enzymatic activity. Because PGHS-1 is a rate-limiting enzyme in the synthesis of prostaglandins, PGHS-2 may also play an important role in prostaglandin production. To examine whether PGHS-2 is induced by phorbol ester in mast cells, we studied mRNA expression of PGHS-2 and also measured prostaglandin D2 (PGD2) production when canine mastocytoma cells were incubated with phorbol myristate acetate (PMA). PGHS-2 mRNA was induced by PMA, with a maximal induction after 4 h of incubation with 10 nM PMA. There was concentration dependent production of PGD2 after incubation with PMA. In contrast, PGHS-1 mRNA was expressed in resting cells, and the expression of PGHS-1 mRNA was down regulated by PMA. Dexamethasone inhibited PMA-induced mRNA expression of PGHS-2 and PGD2 production. Aspirin had no effect on mRNA expression of PGHS-2 but inhibited PGD2 production. In conclusion, PGHS-2 is induced by phorbol ester in canine mast cells. We speculate that PGHS-2 may be important in airway inflammation in which mast cells are activated. PMID- 8217195 TI - Expression of the cyclin-dependent kinase cdk4 in perinatal and adult rat lung. AB - The identification of numerous cyclin-dependent kinases (cdk) and G1 cyclins suggests that cell cycle progression through G1/S may be controlled in a tissue specific manner by various cdk/cyclin complexes. In situ hybridization was used to characterize expression of the cyclin-dependent kinase cdk4 in prenatal and postnatal rat lung and other tissues and to determine whether cdk4 expression is limited to proliferating cells, identified by BrdU incorporation and cdk1 mRNA expression. cdk4 co-localized with cdk1 in proliferating cells of both prenatal and postnatal lung and other tissues, consistent with an SPF function that is not tissue-specific. The distribution of cdk1 and cdk4 expression was identical in fetal rat tissues and was detected in lung parenchyma and throughout the airway. Pulmonary cell proliferation declined with increasing postnatal age and could be found only in focal areas of day 21 terminal and respiratory bronchiolar epithelium. Proliferation was undetectable in adult lung. Postnatal cdk4 expression was not restricted to cells expressing cdk1: cdk4 was evenly distributed in bronchiolar epithelium and was present throughout the airway and alveolar septae of day 21 lung. Expression of cdk4 was also maintained in adult bronchiolar epithelium. These studies demonstrate that although the expression of cdk1 is tightly correlated with proliferative capacity, the expression of cdk4 is not limited to proliferating cells, suggesting that cdk4 may have additional cell specific functions unrelated to cell cycle progression. PMID- 8217196 TI - Expression of muscarinic M2 receptors in cultured human airway smooth muscle cells. AB - [3H]-inositol phosphate formation and the inhibition of isoproterenol-induced [3H]-cyclic adenosine monophosphate (AMP) formation in response to the muscarinic agonist carbachol were studied in cultured human airway smooth muscle cells. Stimulation with carbachol produced concentration-dependent inhibition of isoproterenol (1 microM)-induced cyclic AMP formation (EC50, 0.15 microM; maximal inhibition, 60%). This response was itself reversed by pertussis toxin (100 ng/ml) and was competitively inhibited by the muscarinic antagonists pirenzepine (pA2, 6.5), methoctramine (pA2, 8.0), 4-diphenylacetoxy-N-methyl-piperidine (pA2, 8.0), and parafluorohexahydrosiladifenidol (pA2, 6.5), indicating that the M2 receptor subtype was mediating this response. In addition, carbachol also induced [3H]-inositol phosphate formation in these cells (EC50, 11 microM; 2.1-fold stimulation over basal), although the response observed was markedly down regulated compared with the response seen in noncultured airway smooth muscle preparations. Growth arrest of cells failed to increase the magnitude of the inositol phosphate response to carbachol. These results demonstrate that cultured human airway smooth muscle cells express functionally coupled M2 receptors and probably also low levels of coupled M3 receptors. PMID- 8217197 TI - Human nasal mucosal neutral endopeptidase (NEP): location, quantitation, and secretion. AB - Neutral endopeptidase (E.C.3.4.24.11, enkephalinase, NEP) is a potentially important enzyme capable of regulating the activity of neuropeptides released in the respiratory mucosa. In order to confirm the existence of NEP in the human respiratory mucosa, inferior nasal turbinate mucosae obtained at surgery and nasal secretions induced by topical provocations with methacholine, histamine, and allergen were analyzed for: (1) NEP activity (pmol product/min/ml) by enzymatic degradation of [3H]leu-enkephalin, (2) the presence of NEP immunoreactive material by Western blot analysis, and (3) cellular localization of NEP distribution by immunohistochemistry. NEP activity in human nasal secretions obtained after normal saline challenge was 0.15 +/- 0.06 pmol/min/ml. Secretion increased to 0.86 +/- 0.26 pmol/min/ml after methacholine provocation and 1.69 +/- 0.74 pmol/min/ml after histamine provocation. The increase in NEP activity in methacholine-induced secretions was prevented by atropine (0.13 +/- 0.06 pmol/min/ml). After methacholine, histamine, and antigen nasal provocation, the kinetics of NEP appearance correlated more closely to the glandular marker, lactoferrin, than with the vascular markers albumin and IgG. In homogenates of nasal mucosa, the membrane fraction contained significantly more NEP on a per mg protein basis than did the soluble fraction (227.6 +/- 50.52 versus 9.61 +/- 3.18 pmol/min/mg protein, respectively, P < 0.01, n = 6). NEP in the membrane fraction was detected as a single band migrating at 97 kD on Western blots using antibodies specific for NEP and the common acute lymphoblastic leukemia antigen (CALLA). Immunoreactive NEP was localized to serous cells of the submucosal glands, epithelial cells, and endothelial and myoepithelial cells of small vessels. Staining for NEP in the serous cells was of the same intensity as that in epithelial cells. These results indicate that 97 kD NEP-immunoreactive material exists in discrete locations in the nasal mucosa, including the epithelium, serous cells of the submucosal glands, and vessel walls, and that NEP activity is detected as a minor component in nasal secretions enriched by glandular products. In addition to the modulating functions of NEP on neuropeptide-mediated activities on vessels and glands, it is possible that NEP in secretions plays a role in regulating mucosal responses to luminal neuropeptides or other as yet uncharacterized NEP substrates. PMID- 8217198 TI - Normal anatomy and magnetic resonance appearance of the knee. AB - This article discusses the normal magnetic resonance (MR) appearance, functional anatomy, and biomechanics of the knee joint. Technical considerations of MR imaging of the knee are covered first: coil selection, positioning, and pulse sequences. Useful sequences for both routine examinations and specific clinical situations are suggested. This is followed by a discussion of the biomechanics and functional anatomy of the knee. The typical MR appearance of various key structures in the knee is discussed. The final section of the article is an atlas of normal MR anatomy of the knee, covering the sagittal, coronal, and axial planes. PMID- 8217199 TI - Magnetic resonance imaging of the knee: menisci, ligaments, tendons. AB - Magnetic resonance imaging (MRI) is the technique of choice to depict normal anatomy and to image internal derangements of the knee. The overall accuracy of this method can reach approximately 94%. MRI can effectively replace diagnostic arthroscopy for evaluation of meniscal and ligamentous tears. PMID- 8217200 TI - Lesions of cartilage and bone around the knee. AB - A variety of bone and cartilage abnormalities can be demonstrated on magnetic resonance imaging (MRI), which can play an important role in the diagnosis and management of these abnormalities. Ischemic bone lesions, including medullary bone infarction, primary osteonecrosis, and the osteochondroses, can be precisely evaluated as to their anatomic locations and relationship to overlying cartilage. Osteochondritis dissecans may also be diagnosed and staged. Presence of subchondral fractures and bone contusions, which are frequently associated with ligament and meniscal injuries, can also be diagnosed and followed; these conditions may play a role in the evolution of osteoarthritis. The changes of osteoarthritis, including cartilage abnormalities, cyst formation, and loose bodies, can be evaluated; this evaluation may be important in the assessment of therapies. Stress fractures often have characteristic appearances, and MR may be used in making this diagnosis, especially when symptoms and other imaging are unclear. Diffuse marrow disorders including hemoglobinopathies and neoplasia are also well demonstrated. PMID- 8217201 TI - Magnetic resonance imaging of soft tissue and cystic masses about the knee. AB - Magnetic resonance imaging (MRI) of the knee is the most frequently performed joint MRI examination. The use of MRI has revolutionized assessment of both intra articular and periarticular musculoskeletal masses about the knee and has largely supplanted other radiologic methods of evaluation. The purpose of this article is to review the MRI appearance of the numerous types of soft-tissue and cystic masses that arise about the knee. PMID- 8217202 TI - Intracardiac echocardiographic imaging of cardiac abnormalities, ischemic myocardial dysfunction, and myocardial perfusion: studies with a 10 MHz ultrasound catheter. AB - Intracardiac echocardiography (ICE), an echocardiographic examination from within the heart itself, has been proposed as a new modality for cardiac imaging. A major shortcoming has been the limited depth of field provided by previously available devices. We used 10 MHz catheters for ICE to determine if this lower frequency would allow for greater display of cardiac anatomy. We performed ICE in seven animals; myocardial ischemia was induced in three. With the imaging catheter in the right atrium, all four cardiac chambers and valves could be imaged. Advancing the transducer into the right ventricle allowed for short-axis images of the left ventricle. Coronary perfusion territories and segmental wall motion abnormalities could be observed. We then performed ICE in six patients by advancing the catheter into the right side of the heart percutaneously. Structures of the right side of the heart, the mitral valve, aortic valve, left atrium, and portions of the left ventricle, were visualized. Congenital and acquired abnormalities could be identified. There were no complications. We conclude that ICE with 10F, 10 MHz ultrasound catheters allows for expanded imaging capabilities because of the increased depth of field. With this imaging modality, congenital and acquired abnormalities as well as myocardial ischemia can be detected. PMID- 8217203 TI - Transesophageal echocardiography during repair of congenital cardiac defects: identification of residual problems necessitating reoperation. AB - One advantage of intraoperative transesophageal echocardiographic (TEE) evaluation during surgery for congenital heart disease is detection of suboptimal repairs, thus providing the opportunity to return to cardiopulmonary bypass (CPB) to repair residual defects. The purpose of this study was to evaluate the impact of TEE on decisions to return to CPB. Two-hundred-thirty infants and children with a variety of defects were studied with size-appropriate TEE probes. Patients were grouped by anatomic defect or surgical procedure for which TEE was requested. After CPB, pre- and post-CPB TEE anatomic, functional, and flow evaluations were compared. TEE findings prompted a return to CPB to repair residual defects in 17 of 230 (7.4%) patients. By diagnosis, return to CPB occurred in 9 of 28 (32%) patients with left ventricular outflow tract obstruction, 5 of 78 (6.4%) patients with ventricular septal defect, 1 of 16 (6%) patients with switch-repaired transposition, 1 of 32 (3%) with aortic valve disease, and 1 of 3 with double outlet right ventricle. All post-CPB diagnoses were confirmed during reoperation. Although post-CPB TEE provided reassuring information in patients with other diagnoses, TEE impact on return to CPB appears to be significant in a small group of primary diagnoses. The sensitivity and specificity of TEE determination of the need for reoperation were 89% and 100%, respectively. By identifying the site, severity, and mechanism of residual problems, TEE offers substantial utility in detection of residual problems in need of reoperation. PMID- 8217204 TI - Intraoperative epicardial echocardiography during repair of tetralogy of Fallot. PMID- 8217205 TI - Impact of B-mode color encoding on rapid detection of ultrasound targets: an in vitro study. AB - The purpose of this study was to assess the impact that new B-Mode color encoding schemes have on an observer's ability to rapidly detect ultrasound targets in an in vitro system. Four phantoms were created with five-, six-, or seven-tissue density objects. Each phantom was scanned in routine grey scale (256 grey levels) and in three different color encoding algorithms. A test tape containing 3- and 5 second exposures, in random order, to the different phantoms recorded in grey and B-mode color was then prepared and viewed by 21 observers. Results were tabulated as the mean number of absolute errors in object recognition, per observer, per scan, for both the 3- and 5-second exposures. Each color scheme reduced observer detection error rates compared with error rates with grey scale recordings when viewed for 3 seconds. There was no reduction in error rates when 5-second exposures were viewed. We conclude that in an in vitro system, new B-mode color encoding schemes may facilitate rapid and accurate detection of soft-tissue targets. PMID- 8217206 TI - Pulmonary venous flow: its relationship to left atrial and mitral valve motion. AB - The factors affecting pulmonary venous flow were studied in a group of 50 patients divided into four groups. Group 1 consisted of 14 normal subjects. Group 2 consisted of 10 patients with pure mitral stenosis and normal sinus rhythm. Group 3 consisted of 15 patients with pure mitral stenosis and atrial fibrillation. Group 4 consisted of 11 patients with atrial fibrillation alone. Pulmonary venous flow, atrial septal motion, and mitral valve flow were obtained by transesophageal echocardiography. Pulmonary wedge pressure or left atrial pressure was measured invasively in all patients. We observed that pulmonary venous flow had a reversed flow during atrial contraction and a biphasic flow in the ventricular phase. The first phase of flow occurred during ventricular systole, corresponding to the beginning of atrial relaxation. The second phase of flow, during ventricular diastole, occurred consistently after the rapid filling wave of mitral flow. The beginning of the second phase, corresponding to maximal relaxation of the atrial septum, reached a maximum corresponding to the beginning of atrial contraction. Results of the present study also indicate that decrease or absence of reversed atrial flow and decrease in the first phase of ventricular flow were noticeable in patients in Groups 2, 3, and 4. The second phase of pulmonary venous flow was significantly decreased in patients with mitral obstruction (Groups 2 and 3), but was maintained when the mitral valve was normal (Group 4). In six patients undergoing percutaneous mitral valvuloplasty, the ventricular phase of pulmonary venous flow increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217207 TI - Pitfalls in quantitative contrast echocardiography: the steps to quantitation of perfusion. AB - Current methods used clinically to assess myocardial perfusion are invasive and expensive. As the technology of ultrasound imaging improves, CE may provide a relatively inexpensive, noninvasive means of quantitating myocardial perfusion. Issues regarding stability of microbubble contrast agents must be studied more closely under physiologic conditions. As such, encapsulated microbubbles may provide more stability under physiologic pressures than free gas microbubbles. Introducing high concentrations of contrast, either by hyperconcentrating the contrast agent or by increasing the injection rate, may provide greater stability under physiologic conditions. Further, before quantitative statement of tissue perfusion can be made, the relationship between tracer concentration and system response must be established. Further, a "linear" postprocessing ultrasound setting does not eliminate this requirement as data must still undergo nonlinear transformation during log compression and time-gain compensation. Additionally, issues regarding "electronic thresholding" must be explored more extensively in vivo. Commercial ultrasound scanners, in their present form, may not offer adequate sensitivity for absolute quantitative studies. Further development of modified ultrasound systems may provide sufficient sensitivity for quantitative perfusion imaging. CE offers a potentially powerful tool in the clinical management of patients with ischemic heart disease. Conventional coronary angiography provides information on the size of a lesion, but accompanying tissue perfusion distal to the lesion cannot be determined. Doppler ultrasonography determines velocity of blood flow in large vessels but does not offer the potential to quantitate tissue perfusion. Clearly, CE has a place in the future of diagnostic imaging. The recent work of Ito et al. demonstrated the qualitative potential of CE in the identification of "areas at risk" in patients who had undergone thrombolysis or percutaneous transluminal coronary angioplasty after an acute myocardial infarction. With further improvement in the ultrasound imaging techniques and microbubble stability, CE may offer an inexpensive, noninvasive means of assessing myocardial perfusion. PMID- 8217208 TI - Biplane transesophageal echocardiography in the diagnosis of patent foramen ovale. AB - Patent foramen ovale is associated with unexplained systemic embolic events or persistent hypoxemia. The diagnosis of a patient foramen ovale is based on the existence of an interatrial right-to-left shunt. Biplane transesophageal echocardiography with its increased ability to provide accurate anatomic detail may allow the visualization of the actual opening of the patent foramen ovale. In 19 patients with transesophageal positive contrast studies, we assessed the value of the vertical versus the horizontal plane in the diagnosis of a patent foramen ovale. The patent foramen ovale opening could be seen and sized in the vertical plane in 10 studies (53%). In none of these 10 cases was the opening seen also in the horizontal plane. We conclude that in a significant number of cases, biplane transesophageal echocardiography adds morphological detail to the diagnosis of patent foramen ovale. The ability to size the actual opening may have therapeutic implications. PMID- 8217209 TI - Analysis of mitral inertance: a factor critical for early transmitral filling. AB - The upslope of the transmitral E wave depends on the combined influence of the rate of change of the atrioventricular gradient and the inertial mass of blood within the mitral apparatus (inertance). To use observed transmitral velocity to predict the atrioventricular pressure (delta p) difference requires knowledge of the magnitude of mitral inertance (M, inertial mass divided by effective orifice area), closely related to the length over which blood accelerates and decelerates on passing through the valve. To define the magnitude and determining factors for mitral inertance in typical valvular geometries, we used an in vitro model in which a known atrioventricular gradient (delta p, range 3.8 to 39 mm Hg) was applied instantaneously to orifices (areas of 0.5, 1, 1.5, 2, and 2.5 cm2) and conduits (volume 2.5 to 24 ml). Continuous wave Doppler spectra were recorded and the slope (dv/dt) of the tangent to the upslope was measured manually. From slope and pressure difference, inertance was calculated as delta p/(dv/dt). In 103 combinations of pressure gradients and orifices or conduits, inertance ranged between 1.9 and 12.7 gm/cm2. Linear regression showed that inertance M was highly correlated with orifice diameter D (M = 3.17 D; r = 0.84; p < 0.0001) and, in the conduits, with diameter and length L (M = 4.1 D + 0.7 L-1.8; r = 0.87; p < 0.0001). Inertance was not significantly related to the pressure gradient. In conclusion, inertance depends mainly on the mitral apparatus geometry and most strongly on orifice diameter. Knowledge of mitral inertance should help to extract quantitative data on atrioventricular pressure difference from the upslope of the transmitral E wave. PMID- 8217210 TI - The shape of the proximal isovelocity surface area varies with regurgitant orifice size and distance from orifice: computer simulation and model experiments with color M-mode technique. AB - The hemispheric proximal isovelocity surface area method for quantification of mitral regurgitant flow (i.e., Qc = 2 pi r2v), where 2 pi r2 is the surface area and v is the velocity at radius r, was investigated as distance from the orifice was increased. Computer simulations and steady flow model experiments were performed for orifices of 4, 6, and 8 mm. Flow rates derived from the centerline velocity and hemispheric assumption were compared with true flow rates. Proximal isovelocity surface area shape varied as distance from each orifice was increased and could only be approximated from the hemispheric equation when a certain distance was exceeded: > 7, > 10, and > 12 mm for the 4, 6, and 8 mm orifices, respectively. Prediction of relative error showed that the best radial zone at which to make measurements was 5 to 9, 6 to 14 and 7 to 17 mm for the 4, 6, and 8 mm orifices, respectively. Although effects of a nonhemispheric shape could be compensated for by use of a correction factor, a radius of 8 to 9 mm can be recommended without the use of a correction factor over all orifices studied if a deviation in calculated as compared with true flow of 15% is considered acceptable. These measurements therefore have implications for the technique in clinical practice. PMID- 8217211 TI - A large left ventricular thrombus evolving towards canalization and mimicking a left ventricular pseudoaneurysm: an echocardiographic study. AB - We describe a case of a large apical left ventricular thrombus evolving towards canalization and showing echocardiographic features mimicking a left ventricular pseudoaneurysm. Only serial echocardiographic studies allowed an appreciation of the changing morphologic features of the apical structure, permitting differential diagnosis between a canalization of an evolving thrombus and a myocardial free-wall rupture with pseudoaneurysm formation. PMID- 8217212 TI - Transesophageal echocardiographic demonstration of right coronary artery-to coronary sinus fistula in a heart transplant recipient. AB - A fistula between the distal right coronary artery and coronary sinus was detected by transesophageal echocardiography in a heart transplant recipient. Cineangiograms confirmed this finding to be new since the time of angiography one year earlier. Although coronary artery-to-right ventricular fistulas are not an uncommon complication of endomyocardial biopsy, the echocardiographic findings of a fistula involving the coronary sinus have not been previously described. PMID- 8217213 TI - Right parasternal imaging: an underutilized echocardiographic technique. AB - If the echocardiographer uses only standard imaging planes, he or she may fail to obtain vital information about the aorta, atrial septum, superior and inferior vena cavae, and the coronary arteries. The evaluation of caval-to-systemic venous atrial connections (Senning or Mustard) in transposition of the great arteries of systemic vena caval or right atrial-to-pulmonary anastomosis (Fontan) in tricuspid atresia and single ventricle may not be adequately seen when only the standard left parasternal, apical, subcostal, and suprasternal imaging planes are used. Therefore, the use of the right parasternal imaging plane may help to provide crucial information regarding these areas when the standard views are unable to delineate them adequately. The right parasternal window is an additional echocardiographic window that should become part of a complete echocardiographic examination. PMID- 8217214 TI - Comparison of basic fibroblast growth factor in X-linked dystrophin-deficient myopathies of human, dog and mouse. AB - Binding of polyclonal antibodies specific for bFGF was examined in tissue sections of myopathic and normal muscles from humans, dogs and mice. The proposal tested was that differences in the amount or distribution of bFGF in muscles of the 3 species, might correlate with the limited muscle regeneration seen in humans and dogs afflicted with x-linked muscular dystrophy, in contrast with the sustained new muscle formation in mdx mice with the homologous myopathy. There was a striking difference between the species in the binding of bFGF antibodies to extracellular matrix, particularly at the periphery of myofibres; binding was pronounced in mouse but weak or absent in human and dog muscle. Binding to muscle nuclei and sarcoplasm was also stronger in mice than in humans and dogs, and in all species was more pronounced in foetal than adult muscle. Increased binding of bFGF antibodies was seen in damaged and regenerating muscle cells in all myopathic specimens where these were present. This was associated with the regenerative process rather than with myopathy, as a similar pattern of bFGF expression was seen in mouse muscle regenerating after experimental crush injury. The higher extracellular staining for bFGF around the periphery of mouse myofibres correlated with the successful muscle regeneration in dystrophic mice. Results suggest that bFGF at the fibre periphery might stimulate a local increase in the numbers of muscle precursor cells which can respond to injury in the mdx mouse. PMID- 8217215 TI - Fibroblast growth factor inhibits proliferation of a highly tumorigenic insulin independent teratoma-derived cell line. AB - The present paper examines the effect of basic fibroblast growth factor (bFGF) on the proliferation of teratoma-derived cell lines having increased tumorigenic properties isolated from the non-tumorigenic adipogenic cell line 1246. Although FGF is a mitogen for the non tumorigenic 1246 cells and for the moderately tumorigenic 1246-3A cells derived from the 1246 cells, bFGF inhibits the proliferation and DNA synthesis of the highly tumorigenic PC cells starting at concentration as low as 30 pg/ml. The inhibitory effect of FGF on PC cell growth is irreversible as demonstrated by the inability of the cells to resume proliferation once FGF is removed from the culture medium. Comparison of 125I bFGF binding to the three cell lines was performed. Based on the Scatchard analysis of the binding data, PC cells display only low affinity class of FGF binding sites whereas 1246 and 1246-3A cells presented also high affinity binding sites. The inhibitory effect of FGF on PC cells did not go through activation of a PKC mediated pathway, which is also known to inhibit PC cell proliferation, since FGF inhibition of PC cell growth was still apparent after PKC down regulation. FGF was still able to transiently stimulate the expression of mRNA for early growth associated genes as demonstrated by c-myc and c-fos expression, although it inhibited cell proliferation on PC cells. Our data demonstrate that the highly tumorigenic teratoma cells acquire an inhibitory response for a factor which is growth stimulatory to non-tumorigenic and moderately tumorigenic cells from which they are derived. PMID- 8217216 TI - Optimization of cell culture conditions for the evaluation of the biological activities of the tetrapeptide N-Acetyl-Ser-Asp-Lys-Pro, a natural hemoregulatory factor. AB - The present study attempts to define the difficulties in evaluating the properties of the hemoregulatory peptide AcSDKP using in vitro assays. In fact, in the presence of sera, which are generally added to basic culture media, AcSDKP is catabolized by proteases present in the serum. The kinetics of AcSDKP degradation depends on the nature and on the concentration of the added serum. In in vitro conditions, the half life of this peptide can be increased by the addition of 1 microM captopril, a metalloprotease inhibitor. Thus, these points need to be considered in designing experiments to study the effects of AcSDKP. PMID- 8217217 TI - A monoclonal antibody which inhibits growth of T cell lines. AB - In an attempt to elucidate the intricate structure and possibly the signal transduction pathway of the interleukin-2 receptor (IL-2R) we tried to produce monoclonal antibodies against putative human IL-2R-associated molecules which precipitated from YT2C2 cells with a monoclonal antibody (Mik beta 3) against the human IL-2R beta chain. One of the antibodies obtained (7 x A10) recognizes a cell surface molecule of about 120 kDa (p120). Cross-linking of [125I]-IL-2 and immunoprecipitation with 7 x A10 suggest that the p120 protein may somehow associate physically with the IL-2R beta chain. Although p120 itself did not bind IL-2, and 7 x A10 did not inhibit IL-2 binding to the IL-2R, growth of the human IL-2-dependent cell lines ED40515 and Kit225 was completely inhibited by adding 7 x A10 to the culture at a relatively low concentration (0.2 micrograms/ml). At a higher concentration (2 micrograms/ml) 7 x A10 inhibited the growth of YTC3 and YT2C2 cells expressing IL-2Rs with high and intermediate affinities, respectively. The B cell line FLEB-14 and the erythroid cell line K562, which both express p120 as determined by flow cytometry, but no IL-2R alpha or beta chains showed only slight proliferation changes at high 7 x A10 concentrations. Out of 16 lymphocyte cell lines tested so far, only Molt-4, Raji and Daudi did not express p120, and therefore 7 x A10 did not influence their growth behavior.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217218 TI - The synovium of transgenic arthritic mice expressing human tumor necrosis factor contains a high level of nerve growth factor. AB - We have recently reported that nerve growth factor (NGF) increases in the synovium of patients affected by rheumatoid arthritis and in the synovium of pharmacologically-induced arthritis in animal models. In the present study, we demonstrate that arthritic transgenic mice which carry and express the human TNF gene (Tg197) also express elevated levels of NGF, and that subcutaneous injection of NGF-antibodies attenuates the loss of body weight caused by the development of disease in these mice. Along with our previous findings, which show an increase in the level of NGF during the acute phase of other autoimmune diseases, these results suggest a role of NGF in these pathologies. The functional significance of NGF in rheumatoid arthritis (RA) is currently under study. PMID- 8217219 TI - Regulation of macrophage colony-stimulating factor (M-CSF) production in cultured human synovial fibroblasts. AB - OBJECTIVE: To study the regulation of macrophage-colony stimulating factor (M CSF) formation in vitro by human synovial fibroblast-like cells. METHODS: Human synovial cell explant cultures were established using cells from non-rheumatoid donors. M-CSF antigen was measured by immunoassay, and messenger RNA (mRNA) levels were determined by Northern blot. RESULTS: The cytokines, interleukin-1 (IL-1), tumor necrosis factor alpha (TNF alpha), interferon-gamma (IFN-gamma) and IL-4, increased production of M-CSF above constitutive levels. The presence of the cyclooxygenase inhibitor, indomethacin, potentiated the action of IL-1 on M CSF synthesis, suggesting that an endogenous cyclooxygenase product(s) can down regulate M-CSF formation. Changes in M-CSF mRNA levels paralleled those in protein levels. The glucocorticoid, dexamethasone, and the retinoid, all-trans retinoic acid, stimulated M-CSF formation. The control of M-CSF synthesis in the synovial fibroblasts differs from that for granulocyte macrophage-CSF (GM-CSF) and granulocyte-CSF (G-CSF). CONCLUSION: These results suggest that cytokine stimulated synovial fibroblasts may be a source of M-CSF production in the joints of patients with inflammatory arthritis; as a result, monocyte/macrophages may be activated, leading to perpetuation of the inflammation and destructive events occurring in these lesions. PMID- 8217220 TI - Retrovirally-produced erythropoietin effectively induces differentiation and proliferation of J2E erythroid cells. AB - The J2E erythroid cell line terminally differentiates in response to recombinant human erythropoietin (rHu-epo). Here we demonstrate that retrovirally produced monkey erythropoietin (Zen-epo) is also capable of inducing the final maturation steps of J2E cells in a dose-dependant manner. The hormone committed J2E cells to a pathway of accelerated proliferation, haemoglobin synthesis and morphological changes including enucleation. However, only 6 h exposure to Zen-epo was required to initiate maximum haemoglobin synthesis 72 h later. Significantly, the synthesis of haemoglobin was achieved by concomitantly activating globin production, haem synthesis and iron uptake. Methylcellulose assays revealed that the vast majority of clonogenic cells were able to respond to Zen-epo. These data show that retrovirally manufactured erythropoietin is an effective stimulus for the erythropoietic development of J2E cells in vitro. PMID- 8217221 TI - tie2, a putative protein tyrosine kinase from a new class of cell surface receptor. AB - The cDNA of a novel mouse cell surface receptor (tie2) has been isolated from a mouse lung library. The predicted amino acid sequence of tie2 encodes a protein of 1122 amino acids, with an extracellular domain and an intracellular tyrosine kinase domain bisected by a transmembrane region. The extracellular domain consists of two Ig-like domains, three cysteine-rich domains and three fibronectin type III repeats whilst the intracellular tyrosine kinase domain has a short insert region of 15 amino acids. In vitro transcription/translation of the tie2 cDNA demonstrates that it encodes a glycoprotein of some 145 kDa. The tie2 protein exhibits a high degree of similarity to the cell surface receptor tie, (Partanen, J. et al., (1992) Mol. Cell. Biol., 12, 1698-1707), and together with this protein defines a new class of cell surface receptor. PMID- 8217222 TI - Thymoma: prognostic factors. AB - The relative importance of factors influencing prognosis and survival in the treatment of thymoma is still controversial. Fifty-three patients operated on for thymoma from 1966 to 1990 were evaluated, 14 with myasthenia gravis and 39 without. Survival was analyzed as it related to associated disease, gross invasion by the tumor and the predominant cell type. Follow-up information was obtained in all cases (mean observation time: 11.2 years). A high proportion (51%) of our patients had invasive forms (stages III and IV). The overall 5-, 10- and 20-year survival rates were 52%, 46% and 21%, respectively. Factors indicating a poor prognosis included local invasion (P < 0.0001), predominantly, epithelial histologic features (P = 0.002), tumor-related symptoms and the type of surgical procedure. Myasthenia gravis was not an adverse factor for survival. The degree of tumor invasion was the main prognostic factor and treatment should be planned accordingly. PMID- 8217223 TI - Tracheobronchial healing after lung and heart-lung transplantation. A critical review of 64 anastomoses. The Joint Marseille-Montreal Lung Transplant Program. AB - The authors report on an analysis concerning the healing of tracheobronchial anastomoses after lung and heart-lung transplantation. The present study includes 64 anastomoses selected from a total of 80. Sixteen were excluded because of early postoperative death; none of these deaths was related to an airway complication. Bronchial healing was assessed with bronchoscopic follow-up; the aspect of the suture line was classified according to the grades of Couraud. The initial reference was the examination at 2 weeks postoperatively, which was compared to subsequent follow-ups. At the initial assessment, 42 anastomoses were grade I, 4 were grade II, and 18 were grade III. The subsequent anatomic result was satisfactory for 52 sutures (81%). The complications observed in the remaining patients were malacia in 2, stenosis treated with a stenting device in 4 and dehiscence in 6. The duration of ischemia and postoperative mechanical respiratory support, as well as the proximal or distal location of the anastomosis appeared to be of significant prognostic value. PMID- 8217224 TI - Hyperperfusion and cerebral dysfunction. Effect of differing acid-base management during cardiopulmonary bypass. AB - Alterations in cerebral blood flow (CBF) occurring during cardiopulmonary bypass (CPB), which are thought to be responsible for increased morbidity, are probably related to changes in arterial carbon dioxide during acid-base management. In this study, 70 patients undergoing elective coronary artery bypass surgery (CABS) were randomised to one of two differing, but widely practised, cardiopulmonary bypass acid-base protocols; pH-stat and alpha-stat. Cerebral blood flow was measured during surgery using the xenon-133 isotope clearance technique. Cerebral oxygen metabolism was measured as the cerebral metabolic rate for oxygen (CMRO2) and matching of the cerebral blood flow to oxygen demand as the cerebral extraction ratio for oxygen (CERO2). Detailed neuropsychological tests were conducted in all patients before surgery and repeated at 6 weeks after surgery for assessment of changes in cognitive function. During hypothermic (28 degrees C) CPB, CBF was significantly greater (P < 0.001) in the pH-stat group (41 ml/100 g per min; 95% confidence intervals (CI), 39-43) than in the alpha-stat group (24 ml/100 g per min; 95% CI, 22-26). The cerebral extraction ratio for oxygen indicated a degree of mismatch of cerebral perfusion and demand during CPB in both pH-stat and alpha-stat groups (0.12; 95% CI, 0.11-0.14 and 0.25; 95% CI, 0.22-0.28, respectively). This mismatch was far more pronounced in the pH-stat group than in the alpha-stat group, indicating greater disruption in cerebral autoregulation in the former group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217225 TI - Assessment of neurological injury due to circulatory arrest during profound hypothermia. An experimental study in vertebrates. AB - To investigate brain changes in induced deep core hypothermia (15 degrees C) with circulatory arrest, five groups of neonatal pigs were subjected to cardiopulmonary bypass (CPB), with circulatory arrest (CA) periods varying from 70-120 min. The parameters analysed were: 1. Histology and electron microscopy of the brain six hours post-CPB, 2. Creatinophosphokinase (CPK) from cerebrospinal fluid (CSF), 3. Vasointestinal neuropeptide (VIP) and 7B2 specific neuropeptide both in plasma and brain tissue. The earliest morphological changes were seen after 90 min CA and were highly significant after 120 min arrest. These changes involved mainly the Purkinje cells of the interior half of the cerebellum with vacuolation in their cytoplasm. A rise in CPK in CSF occurred in all piglet groups. The differences among the various groups were highly significant at 2 and 5 h post-CPB. (P < 0.05). Statistically significant differences were not exhibited among the various groups both in serum and brain tissue total mean values of VIP and 7B2 neuropeptides. We suggest that 1. The cerebellar region is the most sensitive where ischemic lesions attain their maximal severity and extent; the frequency and pattern of selective vulnerability of the cerebellum may be related primarily to its pattern of blood supply 2. The maximum time of CA without histopathological sequelae should not exceed 70 min. PMID- 8217226 TI - Inferior epigastric artery for myocardial revascularization. AB - From March 1990 through January 1992, 108 patients undergoing myocardial revascularization had one (91) or both (17) inferior epigastric arteries (IEA) used for myocardial revascularization. The internal thoracic artery (ITA) was used bilaterally in 87 patients. Of the 373 distal anastomoses, 210 (56%) were with the ITA, 130 (35%) with the IEA, and 12 (3%) with the gastroepiploic artery. Nineteen patients (18%) received 21 saphenous veins. When compared with the ITA, the IEA demonstrated a longer harvest time (36.5 vs 29.6 min, P < 0.0001), a shorter usable length (11.9 cm vs 16.5 cm, P < 0.001), and similar flow (49.7 cc/min vs 48.7 cc/min, P = NS). The operative mortality was 2.8%. Two deaths resulted from low cardiac output and the one remaining death from complications of a cerebral vascular accident. The most common major complication was respiratory insufficiency, which occurred in 11 patients (12%). There were two sternal infections (2%), and two abdominal wound infections (2%), none of which were fatal. The IEA is an acceptable additional arterial conduit. It can be safely employed with one or both ITAs. Short-term and long-term patency must be established before preferential use of this conduit is advised. PMID- 8217227 TI - Coronary surgery can be an alternative to heart transplantation in selected patients with end-stage ischemic heart disease. AB - Patients with ischemic heart disease (IHD) low ejection fraction (EF), and congestive heart failure (CHF), are usually referred for orthotopic heart transplantation (OHT). This study reports our experience with coronary artery bypass grafting (CABG) in patients initially referred for OHT, and suggests guidelines to facilitate the choice of procedure (OHT or CABG). Between January 1990 and December 1991, 32 patients with IHD, proposed for OHT, underwent CABG 31/32 patients were male, the mean age was 58 +/- 12 years (40 to 70). Congestive heart failure was present in all patients and was the main symptom. The mean EF was 23 (14 to 31%), mean cardiac index (CI) 2.4 l/min per m2 (1.6 to 3.1 l/min per m2), mean pulmonary artery mean pressure (MPAP) 26 (20 to 37 mmHg) and mean pulmonary wedge pressure 16 (12 to 22 mmHg). Every patients underwent a myocardial viability study by thallium scintigraphy (n = 32) and/or by positron emission tomography (n = 10). The perioperative mortality was 9.3% (3/32). All long-term survivors (n = 27) are in NYHA Class II with a complete follow-up (mean 18 +/- 6 months). Ejection fraction control either by angiography (n = 15) or by single photon emission computed tomography (n = 12) showed an increase of up to 38% (22%-46%). Three determinant factors influenced the choice of CABG. 1) CI > 21/min per m2, 2) MPAP < 35 mmHg. 3) Detection of myocardial viability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217228 TI - Intramyocardial electrogram recordings for diagnosis and therapy monitoring of cardiac allograft rejection. AB - The registration of intramyocardial ECG amplitudes (IMEG) is a non-invasive diagnostic method of monitoring cardiac allograft rejection. In order to detect possible sources of error IMEG signals were recorded in heterotopic neck hearts in ten beagle dogs. Immunosuppression was based on cyclosporin A. The rejection process was followed by IMEG registrations as well as by serial myocardial biopsies. Intramyocardial electrogram recordings were made via three unipolar and three bipolar leads obtained from screw-in electrodes in both ventricles and the apex of the allograft. A 10% voltage drop was used as an indicator of rejection. In four dogs, the first rejection episode was treated with methyl-prednisolone and the therapy's success was monitored by IMEG and repeat biopsy. At autopsy the histology of each electrode circumference was correlated with the corresponding IMEG. The average sensitivity of a single lead was not acceptable (unipolar: 28%, bipolar: 47%). When the voltages of different leads were summed up the sensitivity rose to 43% (3 x unipolar), 85% (3 x bipolar) and 100% (all leads). During rejection therapy the IMEG recovered within 24-48 h. We conclude that in moderate allograft rejection (grade 2/3a ISHT classification), the rejection related changes of intramyocardial ECG voltage amplitude (IMEG) seem to follow a "focal pattern" similar to the histology. Therefore the recording of several, preferably bipolar, electrode configurations appears to enhance adequate diagnostic reliability. PMID- 8217229 TI - Delayed brachial plexus paralysis due to subclavian pseudoaneurysm after clavicular fracture. AB - Injuries to the brachial plexus and subclavian artery are serious complications of shoulder girdle trauma. Due to the close anatomical relationship between the brachial plexus and the subclavian artery in the thoracic outlet, both structures are often simultaneously involved in shoulder girdle injuries. Isolated lesions of the subclavian artery or the brachial plexus can also occur, especially with clavicular fractures. When a false subclavian aneurysm leads to a gradually increasing compression of the brachial plexus, the neurological signs and symptoms develop insidiously after the traumatic event. PMID- 8217230 TI - Left ventricular free wall rupture after coronary artery surgery. AB - A patient who had undergone urgent coronary artery bypass grafting for unstable angina developed a fatal left ventricular free wall rupture in the early postoperative period. Heart rupture following surgical revascularisation has not been reported before. PMID- 8217231 TI - Primary sternal osteomyelitis. AB - Primary sternal osteomyelitis is a rare condition. Only few cases have been reported in the English literature. We describe the case of a young woman presenting with persistent fever and chest pain. Radionuclide bone scan and computed tomography of the chest were consistent with metastatic neoplasm. Surgical intervention, however, revealed primary staphylococcal osteomyelitis and the patient was successfully treated with combined extensive surgical debridement and intravenous antibiotics. PMID- 8217232 TI - The status of high-energy photon and electron beam dosimetry five years after the implementation of the IAEA Code of Practice in the Nordic countries. AB - The status of the dosimetry of high-energy photon and electron beams is analysed, taking into account the main developments in the field since the implementation of the IAEA Code of Practice in the Nordic countries. In electron beam dosimetry, energy-range relationships are discussed; Monte-Carlo results with different codes are compared with the experimentally derived empirical expression used in most protocols. Updated calculations of water-to-air stopping-power ratios following the changes in the Monte-Carlo code used to compute actual Sw,air values are compared with the data included in most dosimetry protocols. The validity of the commonly used procedure to select stopping-power ratios for a clinical beam from the mean energy at the phantom surface and the depth of measurement, is analysed for 'realistic' electron beams. In photon beam dosimetry, calculated correction factors including the effect of the wall plus waterproofing sleeve and existing data on the shift of the effective point of measurement of an ionization chamber, are discussed. New calculations of medium to-air stopping-power ratios and their correlation with the quality of the beam obtained from the convolution of Monte-Carlo kernels are presented together with their possible practical implications in dosimetry. Trends in Primary Standard Dosimetry Laboratories towards implementing calibrations in terms of absorbed dose to water are presented, emphasizing controversial proposals for the specification of photon beam qualities. Plane-parallel ionization chambers are discussed regarding aspects that affect determinations of absorbed dose, either through the different methods used for the calibration of these chambers or by means of correction factors. Recent studies on the effect of the central electrode in Farmer-type cylindrical chambers are described. PMID- 8217233 TI - Treating acute leukaemias--a venture into economic uncertainty? A method for estimating the cost of treating patients with acute myelocytic leukaemia. AB - The objective of this paper is to report a method for estimating the cost of treating acute myelocytic leukaemia (AML). It is based on individual data from 54 patients treated with aggressive induction courses of chemotherapy. The study records the cost of the entire survival period for 40 patients and of at least 16 months' survival for the remaining 14 patients. All treatment activities were registered from the patient records and the price of each activity was estimated. As far as possible the principle of opportunity cost was used. The median survival time was 50 weeks and the average cost per patient was c. 300,000 SEK (= c. USD 50,000) in 1988 prices. A young man who achieved three remissions and lived for five years had the highest cost, c. 1 million SEK (= USD 155,000). The costs for AML treatment was higher in the 1980s than in the 1970s but led to longer survival for patients who survived the initial period. PMID- 8217234 TI - Non-Hodgkin's lymphoma in northern Sweden. Prognostic factors and response to treatment. AB - A total of 352 cases of non-Hodgkin's lymphoma reported to the Cancer Registry of Northern Sweden during 1978-1982 were retrospectively analysed. After morphologic review, 327 cases classifiable as low (n = 162) or high-grade (n = 165) according to the Kiel classification remained for further study. The purpose of the study was to evaluate the interrelations between some variables and their bearing on prognosis in an almost unselected clinical material. Age, morphological grade of malignancy, clinical stage, systemic symptoms, bulk of disease and serum lactate dehydrogenase (LDH) level turned out to be associated with the clinical outcome in terms of response to treatment, disease-free survival and survival. In the heterogenous group of low-grade lymphoma, six pretreatment characteristics were negatively associated with survival in a univariate analysis, namely; stage II IV, systemic symptoms, bone marrow infiltration, two or more extranodal sites, elevated LDH and age above 65 years. In high-grade lymphoma, stage II-IV, bone marrow infiltration and elevated LDH predicted a worse prognosis in a multivariate analysis. The impact of the number of these prognostic factors on survival in high-grade lymphoma was demonstrated. PMID- 8217235 TI - Survival rates in lung cancer patients with and without bronchial asthma. AB - Bronchial asthma itself or the treatment of asthma may modify the immunological response to cancer. The survival of lung cancer patients with a preceding diagnosis of bronchial asthma was compared with that of non-asthmatic lung cancer patients in Finland during 1970-1989. This was accomplished by linking two nation wide data registers, the medication reimbursement register and the cancer registry. For 921 out of the 926 asthmatic patients with lung cancer diagnosed after the diagnosis of bronchial asthma, a non-asthmatic referent patient, matching with respect to sex, anatomical site, and histological type of tumour, as well as to age and year of lung cancer diagnosis, was successfully found in the files of the Cancer Registry. Another referent group was formed by using the stage of lung cancer at diagnosis as an extra matching criterion; this search was successful for 895 asthmatic lung cancer patients. The corrected 5-year survival rate of asthmatic lung cancer patients was 8.4% and that of the referent patients, not matched for stage, 9.6%. When stage was included as matching criterion the corresponding rates were 8.5% and 8.1% respectively. None of these differences were significant. The prognosis of asthmatic and non-asthmatic lung cancer patients thus seemed to be similar. PMID- 8217236 TI - Ig-gene and T-cell receptor gene rearrangements in a secondary, mono-histiocytic malignancy. AB - In 1984, a 21-year-old male was diagnosed with an acute lymphoblastic leukemia of pre-B cell type. Treatment with chemotherapy, including alkylating agents and prophylactic radiotherapy to the central nervous system, induced a complete remission. In June 1990, a biopsy from a supraclavicular node revealed a malignancy of mono-histiocytic type with erythrophagocytosis. Soon thereafter bone marrow involvement was found. No remission was achieved and the patient died in December 1990. DNA from bone marrow and lymph node obtained 1990 showed clonal rearrangements of both the immunoglobulin heavy-chain gene and the T-cell receptor gamma chain gene. This unusual case illustrates a typical secondary malignancy proven to be separate from the primary neoplasm judged by morphological appearance, immunophenotype and cytogenetic constitution. Coexistent clonal rearrangements of immunoglobulin and T-cell receptor genes have been reported in acute non-lymphoblastic leukemias and notably in cases expressing TdT, interpreted as a predominant lymphoid commitment of the tumor cells. In the present case, however, the malignant cells had a differentiated phenotype and showed erythrophagocytosis, indicating a more mature mono histiocytic cell type. However, also CD3 expression was found by immunohistochemistry of frozen sections which might indicate a biphenotypic malignancy. PMID- 8217237 TI - Prognostic factors in patients with nasopharyngeal carcinoma. AB - From 1971 to 1985 a total of 122 patients with non-distant metastatic nasopharyngeal carcinoma were treated at the Norwegian Radium Hospital with radiation doses that increased from 50 Gy (at 2 Gy/fractions) to 70 Gy (at 2 Gy/fractions) during the treatment period. Possible relationship between the increase in dose and survival time was investigated. The median cancer-specific survival time was 50 months, and the median crude survival time 38 months. No correlation was found between radiation dose and survival time. In a multivariate analysis histology was found to be the most important prognostic factor for survival with a relative risk of death from cancer of 3.4 and 3.2 for non keratinizing carcinoma and squamous cell carcinoma respectively compared with undifferentiated carcinoma. When assessed in terms of N category the relative death risk for N2/N3 was 2.1 compared to N0/N1. PMID- 8217238 TI - A phase I study of escalating interferon alpha-2a combined with 5-fluorouracil and leucovorin in patients with gastrointestinal malignancies. AB - On the basis of preclinical data showing synergy between 5-fluorouracil (5-FU), leucovorin (LV) and IFN-alpha-2a, a phase I study was carried out to determine the maximum tolerable dose (MTD) of IFN-alpha-2a with this combination in patients with gastrointestinal malignancies. The treatment consisted of 370 mg/m2 5-FU and 200 mg/m2, LV on days 1 to 5, and IFN-alpha-2a on days 1 to 5 of the first week of chemotherapy and on days 1, 3, 5 of each subsequent week, on a 28 day cycle. Six patients with colorectal, 3 with pancreas, 2 with oesophagus, 2 with hepatocellular and one with gastric cancer were treated. At level III (5 x 10(6) U/m2) all patients experienced grade 3 or 4 toxicity during the first 56 days of treatment and the MTD was declared level II. Grade 3 toxicity comprised of anorexia, mucositis, diarrhoea, and fatigue; in one instance, grade 4 neutropenia occurred. Ten patients were evaluable for response, one patient with an oesophageal cancer had a minor response and one patient with rectal cancer and liver metastases had a radiological complete response lasting 3 months. The recommended dose for this schedule in phase II studies is 5-FU 370 mg/m2, LV 200 mg/m2, and IFN-alpha-2a 4 x 10(6) U/m2. PMID- 8217239 TI - A randomized feasibility study evaluating the effect of radiotherapy alone or combined with 5-fluorouracil in the treatment of locally recurrent or inoperable colorectal carcinoma. AB - The effect of radiotherapy alone or given simultaneously with 5-FU in the treatment of locally recurrent or inoperable colorectal carcinoma was investigated in a randomized feasibility trial. Twenty-nine patients were randomized to radiotherapy alone (50 Gy/5 weeks + 10-20 Gy boost), and 30 patients to the same radiotherapy with weekly 5-FU (600 mg/m2) given before treatment every Monday during the first 5 weeks. The two groups were comparable with regard to age, sex, previous treatment, symptoms, tumour size and performance status. Treatment compliance to radiotherapy was the same in both groups with 87% receiving at least 50 Gy. Drug treatment was completed in 18/30 patients. Overall the treatment resulted in a significant palliative effect in 73% of evaluable patients with a median duration of 26 months, and objective response in 32% (8 CR, 11 PR), with a median duration of 18 months. The 3-year actuarial survival rate was 9% (median 12 months). Only patients who achieved CR became long-time survivors (63% 3-year actuarial survival). Similarly, performance status had a strong association with survival. Multivariate analysis showed complete response and high performance status to be the only parameters having prognostic influence on survival. Addition of 5-FU did neither influence the objective or symptomatic response, nor the development of distant metastases. However, addition of the drug resulted in an apparent increase in the frequency of severe acute radiation complications (33% vs. 13% after irradiation alone). PMID- 8217240 TI - Relation between preoperative CT findings in rectal cancer and local recurrence rate. A pilot study. AB - To identify predictive factors of local recurrence possible to use as criteria for preoperative radiotherapy, we reviewed the CT scans of 51 patients undergoing curative resection for rectal cancer. Seven patients developed local recurrence. The presence of the CT images of spicular structures or a fibrous soft tissue layer around the rectum was related to extrarectal spread with a positive predictive value of 88% (30/34) when compared with the pathology. Six out of 34 cases with these CT findings developed recurrence, compared to only one out of 17 cases without such findings. The recurrence rate was especially high, (4/14), in patients where the abnormal tissue as judged by CT was attached to the perirectal fascia or extended beyond it. CT may be a useful tool for predicting local recurrence by using the perirectal fascia as a diagnostic marker. PMID- 8217241 TI - Definitive radiotherapy for carcinoma of the oral tongue. AB - This is a retrospective analysis of 117 patients with carcinoma of the oral tongue treated by definitive radiotherapy during 1979-1990. Sixty-seven per cent of patients presented with T1-2 disease. Their cumulative incidence of local failure was 10% (5/50) for those suitable for treatment with implant alone, 81% (13/16) for those treated with external irradiation alone and 67% (8/12) after combined treatment. These differences could largely be explained by selection factors as smaller and less bulky tumours generally were selected for implant treatment. Among the patients who achieved local control, there was no incidence of regional relapse (0/9) for those with elective neck irradiation, but 33% (15/46) for those without. This incidence correlated with size of primary tumour. Radiotherapy achieved effective local control in 13% (5/39) of T3-4 tumours, and regional control in 43% (12/28) of N1-3 cases. Only 32% (24/76) of patients with local and/or regional recurrence were successfully salvaged. Ways of improving the treatment are discussed. PMID- 8217242 TI - Radiation effects in the colon. An experimental study in the rat. AB - In an experimental study, resembling a clinical trial of preoperative irradiation, 10 + 10 Gy was given to the pelvic and lower abdominal region of rats with a 4-day interval. The early effect on the colonic wall was evaluated by myeloperoxidase activity and hydroxyproline content of the bowel wall and correlated to histological findings. Groups of animals were followed up to eight months after irradiation for evaluation of later effects. General effects of irradiation were seen as low WBC during the first week and delayed body weight development up to two months after irradiation. Local effect in the colonic wall was noted as an increase in myeloperoxidase activity (indicating a leucocyte accumulation) in irradiated parts of colon during the first 11 days and again significantly elevated after two months in parts of colon, irradiated as well as protected. This correlated well with histological findings of inflammatory reaction, atypia and dysplasia during the first 10 days after irradiation but not at two months after irradiation. Hydroxyproline content was not affected. There were no major complications due to irradiation seen in the late course of the study period. PMID- 8217243 TI - Bronchopulmonary carcinoids associated with Cushing's syndrome--report of a case and an overview of the literature. PMID- 8217244 TI - Effects of combined tamoxifen and medroxyprogesterone treatment on coagulation fibrinolytic systems in patients with advanced breast cancer. PMID- 8217245 TI - [In Portugal barely one of every 10 patients with an indication for therapy by percutaneous transluminal coronary angioplasty had access to this technic in 1991]. PMID- 8217246 TI - [In praise of prevention]. PMID- 8217247 TI - [The diagnosis and ablation of accessory atrioventricular pathways in the initial electrophysiological exam: a new therapeutic modality in pre-excitation syndromes]. AB - OBJECTIVE: To describe the experience and results in the diagnosis and catheter ablation of atrioventricular accessory (AP) pathways during the initial electrophysiologic study. DESIGN: We performed catheter ablation at the time of an initial electrophysiologic study in 22 consecutive patients (12 W and 10 M, mean age 42 +/- 15) with Wolff-Parkinson-White syndrome or supraventricular tachycardia. SETTING: Cardiology Department at University Hospital. INTERVENTIONS: The precise AP mapping was performed with the ablation catheter (4 mm distal electrode and deflectable tip) according to the earlier ventricular activation during sinus rhythm or the earlier atrial activation during ventricular pacing or orthodromic reentrant tachycardia. For left-sided pathways the ablation catheter was positioned on the mitral annulus retrogradely across the aortic valve, while for right-sided pathways it was positioned on the tricuspid annulus or near the coronary sinus os. Radiofrequency energy was applied for 20-60 segs with 55-65 Volts. MEASUREMENTS AND RESULTS: Seventeen AP were manifest and five were concealed. AP were left lateral in 11 patients (50%), left posterior in 5, and right postero-septal, right posterior or antero-septal in 2 patients each. The ablation was initially successful in 18/22 (82%), with 9 +/- 8 radiofrequency applications. Mean duration of the entire procedure was 145 +/- 59 min and the fluoroscopy duration was 39 +/- min. There were no major complications. During 2-9 months of follow-up AP conduction returned in two patients. CONCLUSIONS: Radiofrequency catheter ablation of AP is effective and safe and can be performed at the time of an initial electrophysiologic test, avoiding the need for long-term antiarrhythmic drug therapy or surgical ablation. PMID- 8217248 TI - [Fever in the first 48 hours of an acute myocardial infarct treated with fibrinolytics--an indicator of nonreperfusion of the coronary vessels?]. AB - Fever in the first days of acute myocardial infarction (AMI) is a very common clinical feature, being its prognostic value unquestionable. As infarction area reduction implies a less important fever reaction in the first days of AMI, we believe that thrombolytic therapy would result in a decline of body temperature of patients so treated. That is why we tried to identify such a correlation, and demonstrate the value of normal body temperature as indicative of reperfusion. We studied retrospectively 68 patients (10 F and 58 M, 57.1 +/- 9.6 years) survivors of AMI (I-II KK classes), with (TT) or without (NT) thrombolytic therapy. In NT group, there was an axillary temperature (AX T) higher than 37 degrees C at the first 24 hours in 21 patients (62%); TT group only had 10 patients (30%) with AX T over 37 degrees C (p < 0.01). NT group CK mean peak was 856 +/- 610 U.I./l in patients having AX T > 37 degrees C, and 436 +/- 233 U.I./l when AX T was < or = 37 degrees C (p < 0.05); in TT group there was no difference between CK peak means when AX T was > or < or = 37 degrees C (1508 +/- 1210 U.I./l vs 1406 +/- 1149 U.I./l, respectively) (NA). We established statistic difference between AX T of 15 patients which CK peak was reached after 10 hours over onset of AMI (37.59 +/- 0.36 degrees C) and those (19 p) with CK peak before 10 hours (37.17 +/- 0.60 degrees C) (p < 0.05). NT group presented then more febrile patients than did TT group. CONCLUSIONS: in NT group there was a positive relation between AX T and CK peak level; AX T > 37 degrees C was less frequent in TT group and was as much light when CK peak was more precocious. These results suggest that in thrombolytic treated patients the absence of fever in the first 48 hours may constitute one more coronary reperfusion criterion. PMID- 8217249 TI - [Risk stratification in non-Q-wave myocardial infarct]. AB - There was been some controversy about non-Q wave myocardial infarction, its evolution and prognosis. The most recent studies showed that, in spite of the low immediate mortality in non-Q wave myocardial infarction, the long-term risk of ischaemia, reinfarction or sudden death is equal or even greater than in the Q Wave myocardial infarction. In order to define an adequate ischaemic risk stratification strategy in the post non-Q wave myocardial infarction without complications, the authors studied 21 patients who were submitted to treadmill exercise test and coronary angiography within 30 days after the acute event. Of the 17 patients with positive stress testing, 14 showed significant relationship between ischaemic area detected in the stress testing and the anatomic localization and severity of the lesions in the coronary angiography (chi 2 = 14,875; p < 0.006). Revascularization therapy (PTCA or bypass surgery) was very high in this group of patients (47.6%). From the date obtained the authors conclude that it is not necessary to use invasive studies in every patient that has suffered from non-Q wave myocardial infarction without complications, since the stress testing showed high sensitivity (94.4%), specificity (75%) and high predictive value (100%) in the ischaemic risk stratification. PMID- 8217250 TI - [The determination of the mitral valve area after commissurotomy. A comparison of 2 echocardiographic methods]. AB - OBJECTIVE: To compare the mitral valvular area obtained by two-dimensional echocardiography (2DMVA) to that obtained by Doppler through pressure half-time, (T1/2P) method (DMVA) in patients submitted to open or closed commissurotomy. POPULATION: Data were obtained from 53 patients, 44 females and 9 males who ranged in age from 19 to 63 years (mean = 40.4 +/- 8) submitted to open commissurotomy (group A) or closed procedure (group F). The time from surgery to Echo ranged from 10 to 100 months (mean = 63 +/- 26). Ther were twenty one patients, in group A and 32 in group F. METHODS: All the patients underwent two dimensional echocardiography and continuous-wave doppler, guided by image and sound, so that the maximum velocity was located, using a Diasonics DRF 300 machine equipped with a combined echo-Doppler 3.5 mHz transducer. The mitral valve was visualized in short axis view the 2D mitral valve area was measured as the planimetered area along the inner border of the smallest orifice, while scanning through the short axis. Continuous-wave Doppler recordings were performed at 50 mm/s. The pressure half-time was measured as the interval between maximum velocity and maximum velocity/1.4. The valvular area (DMVA) was obtained by the expression 220/T1/2p. Maximum velocity (VMax) of mitral flux and the prevalence of significant mitral regurgitation (> = 2) were also compared in groups A and F. The relationship between 2DMVA and DMVA were compared by simple linear regression analysis and the other parameters by the t test and by chi squared analysis. RESULTS: 2DMVA in the total patients was 2.26 +/- 0.59 and the DMVA 2.31 +/- 0.76 (NS). There were no significant difference between groups A e F concerning: VMax = 162.48 +/- 28.15 and 150.09 +/- 30.08, DMVA = 2.34 +/- 0.75 and 2.29 +/- 0.76 respectively, and mitral regurgitation = 2 patients in both groups. The correlation between the Doppler and the 2D obtained areas was good in group A r = 0.76 SEE there were no correlation between these values in group F r = 0.33. CONCLUSIONS: We can conclude that the mitral valvular area obtained by two-dimensional echocardiography, correlates to the Doppler mitral valvular area in patients with prior open commissurotomy proving the complementary role of the two methods. PMID- 8217251 TI - [Malignant vasovagal syncope: a case of prolonged asystole induced by the "tilt" test and aggravated by therapy with a beta blocker (a clinical case and diagnostic, physiopathologic and therapeutic review)]. AB - The authors describe a case of a middle-age male with recurrent syncope, in whom the tilt test was useful in the diagnosis and therapeutic evaluation. Malignant criteria of vasovagal syncope were established and the beta blocking worsening effect was documented, in spite of the general agreement of the first choice drug. PMID- 8217252 TI - [Stress echocardiography]. PMID- 8217253 TI - [The sensitivity and specificity of the ergometric test for the diagnosis of coronary disease]. AB - According to the principles of probabilistic analysis, sensitivity and specificity of a diagnostic test are fixed values. Nevertheless, most authors consider them to be inconstant values, specially when applied to the diagnosis of coronary heart disease by exercise stress test. In this paper, we review the basic concepts on sensitivity and specificity of diagnostic tests and try to explain their supposed variability, when related to exercise test, as a function of undue comparison between ST-segment response and the findings of cinecoronariography. Based on the essential difference between coronary heart disease and ischemic heart disease, we demonstrate why such an equivocal comparison can lead to false results of sensitivity and specificity of exercise tests relative to coronary heart disease. As a result, their alleged variability depends most on the prevalence of ischemia throughout the spectrum of coronary heart disease in the studied population. As a matter of fact, unless one can rely on a method as a gold standard for the diagnosis of ischemic heart disease, the real sensitivity and specificity of exercise stress test should be considered as unknown values. PMID- 8217254 TI - [The role of the vascular endothelium and vasospasm in different coronary syndromes. A common physiopathological base for distinct entities?]. AB - A literature review on the endothelial functions and endothelial dysfunction/lesion, as well as the atherosclerosis role in this process is performed. The several physiological explanations of both acute and chronic coronary syndromes are also reviewed, with particular emphasis to the recent studies on vasospasm mechanisms and its role in the physiopathogeny of variant angina and syndrome X. The role of the endothelial dysfunction/lesion as a common physiopathological basis to all coronary syndromes, is discussed. PMID- 8217255 TI - [Research-based thinking of nurses at the end of their basic nursing education]. AB - The purpose of this study was to find out the level of research-based thinking that students have internalized during their professional education. The research based thinking of students has been investigated by analyzing the study reports, they have made at the end of their professional education. "The research-based thinking" is evaluated from the perspective of a research consumer. So, the purpose of this study was not to evaluate the level of studies, but the basis of them. The data consisted of 51 study reports. The data was analyzed by using the content analysis and descriptive statistics. The content analysis was based on the set of general rules for research using deductive methods of approach. The students' problems in research-based thinking fell mainly into the following parts: (1) the students did not use previous studies to build up the frame and the problems of their study, the students used scientific publications limitedly, it seems that the knowledge had the same value to the students regardless of the reference they have taken it from; (2) the students had difficulties in connecting the empirical part of their study with theoretical or conceptual frame. In this study the results indicated, that Finnish nursing students' research-based thinking is not mature in their study-reports at the end of education. It seems important to do further research to be able to analyze the reasons for these findings and how education could be improved in the future. PMID- 8217256 TI - [Family dynamics of mothers and fathers expecting their first or second child]. AB - This study forms part of the international family dynamics project. The study was carried out in two stages. In stage one the aim was to determine how expectant mothers and fathers view the family's activity on six bipolar dimensions (Barnhill 1979). Family dynamics was studied during the third trimester of pregnancy with both mothers (118) and fathers (118) participating in the study (N = 236). The data were collected by questionnaires, using the Family Dynamics Measure. Most parents (86%) reported that their family functioning was either very good or quite good. Married parents reported more stability, flexibility and clearer communication than cohabiting parents did. Mothers reported more flexibility, mutuality and clearer communication than fathers did. Families expecting their first child found more mutuality, role reciprocity and clearer communication than did families expecting their second child. PMID- 8217257 TI - [Research in nursing science: an analysis of research conference abstracts]. AB - The purpose of this study is to describe the current state of research in nursing science and to compare the research done in the USA and Canada with that in other countries. The data consist of 367 research abstracts submitted for conference, which were analyzed in terms of focus, purpose and methodology. The statistical significances of differences were tested using the chi-square test. Most of the research was focused on patients and very little on nursing education or administration. The purpose was in most cases the conceptualization and description of phenomena. A fifth of the abstracts were concerned with the development and evaluation of forms of treatment or interventions, these being more often from the other countries than from the USA and Canada. The data had mostly been gathered by questionnaire, the second most frequent method being interview. Interviews were more often used in the other countries (33%) than in the USA and Canada (24%), where biophysiological measures were used equally often. Most studies were quantitative and only 15% were qualitative. Multivariate analyses were used more often in the USA and Canada than elsewhere. Most of the research analyzed here was carried out in the USA and Canada, and since the group of other countries was very heterogeneous, the results of this study cannot be generalized except in as far as they concern North America. PMID- 8217258 TI - [Human philosophy in empirical human research and promotion of a professional foundation]. PMID- 8217259 TI - Fetal echocardiography. PMID- 8217260 TI - Noninvasive imaging techniques. PMID- 8217261 TI - Doppler velocimetry in pregnancy. AB - Since the late 1970s, Doppler velocimetry has been investigated extensively for use in obstetrics. Initially, this technique showed promise for the management of certain complications of pregnancy; this promise has yet to be fulfilled. Doppler velocimetry of either the uterine or umbilical vessels, which showed some merit in selecting growth-retarded fetuses at particular risk, has neither become a screening tool for intrauterine growth retardation nor proven clinically successful in improving fetal outcome. Likewise, its use for other complications of pregnancy (eg, postdate pregnancy, twin pregnancy, and diabetes) has not led to improved pregnancy outcome. More recently this technique has been used to study other vascular beds. Changes in the Doppler characteristics of these vascular beds may demonstrate the fetal response to its environment. These investigations provide the potential for a better understanding of fetal physiology; however, it has yet to be shown by prospective evaluation that their application results in improved pregnancy outcome. This review defines the uses and limitations of Doppler ultrasound in current obstetric practice. PMID- 8217262 TI - Basic technique of fetal echocardiography. AB - The fetal heart is the organ system most commonly affected with congenital disease. Though risk factors exist for congenital heart disease (eg, family history, toxin exposure, maternal illness, abnormal karyotype, and other fetal anomalies), the fetal heart is most often examined as part of a routine evaluation of the fetal anatomy in the fetus with no identifiable risk factors. The importance of a systematic, complete assessment of the cardiac axis cannot be overemphasized. All aspects of sonography (ie, real time, M-mode, pulsed, and color Doppler) can provide unique and integral information in evaluating the fetal heart and thorax. PMID- 8217263 TI - Contributions of color Doppler to the evaluation of cardiovascular abnormalities in the fetus. AB - The applications of color Doppler sonography are reviewed in this article. Color Doppler is an efficient and time-saving means of assessing normal and abnormal flow in the fetus, making it an essential part of the echocardiographic examination for fetal congenital heart disease. In survey mode, color Doppler can be used to quickly evaluate whether flow channels are normal and to detect abnormal flow patterns. These abnormal flow patterns can then be examined further by pulsed or continuous wave Doppler, if needed. Color Doppler, which is subject to less rib shadowing than other Doppler techniques, also can help in assessing the fetal heart when there is less-than-adequate gray scale imaging. PMID- 8217264 TI - Sonographic assessment of fetal cardiac arrhythmias. AB - The fetus with an arrhythmia may be at high risk both from the arrhythmia itself and from the condition that provoked it. Incorrect diagnosis and inappropriate or delayed treatment may further compound the hazard. Although echocardiography can specifically identify the arrhythmia, this technique requires very skilled and careful examination by a physician who fully understands how to differentiate optimally between similar-appearing but mechanistically different arrhythmias. Congenital heart disease may also be present and must be evaluated specifically. This report describes ultrasound recording techniques used to diagnose arrhythmias and includes a discussion of M-mode echocardiography, two-dimensional imaging, pulsed Doppler, and color-flow Doppler. It also differentiates specific arrhythmias--premature atrial contractions, ventricular tachycardia, atrial flutter, complete heart block, and supraventricular tachycardia--and presents the optimal diagnostic tools for each. PMID- 8217265 TI - Sonographic differential diagnosis of fetal cardiac abnormalities. AB - Ultrasonographic evaluation of the fetal heart for structural and functional abnormalities is vital for prenatal diagnosis and perinatal management. Even more important than up-to-date diagnostic equipment is keen observation and an understanding of fetal cardiac abnormalities. One diagnostic approach begins with the four-chamber view with particular attention to the normal symmetric sizes of all four cardiac chambers. Ventricular disproportion, inequality in ventricular size, is often an easily detectable sign of a cardiovascular abnormality. Segmental diagnosis of cardiac and visceral situs, ventricular outflow tracts for conotruncal abnormalities and the aortic and ductal arches is also vital for diagnosing affected fetuses. PMID- 8217266 TI - [Electroglottography in the research and physiology of larynx]. AB - Electroglottography (EGG) is a noninvasive method of monitoring the movement of the vocal folds by measuring the variation of impedance to a weak alternating current through the tissues of the neck. Basically EGG is an index of the vocal fold contact area. Despite recent controversy EGG continues being an easy to handle method in larynx basic research, with increasing use in clinical diagnosis and rehabilitation of vocal pathology. EGG technique is described and some of its applications in clinical practice and voice research are pointed out. PMID- 8217267 TI - [Distortion of otoacoustic emission]. AB - We present a review of the current literature and our experience with distortion product otoacoustic emissions. They represent a new tool for the clinical study of deafness as shown and of the basic functional status of the cochlea. PMID- 8217268 TI - [The impact of Spanish otolaryngology on the international scientific community in 1981-1990]. AB - The number of papers published by spanish otolaryngologists, as well as the number of citations received in journals indexed in the Science Citation Index CD ROM during 1981-1990, were studied. The survey revealed a total of 87 papers published, with 40 of them on basic research, and 195 citations. Finally, the need of a research development in this field is stressed. PMID- 8217269 TI - [The presence of antibodies directed against specific cartilagenous collagens in patients with otosclerosis]. AB - The etiology of otosclerosis is unknown. Some investigators showed the presence of high levels of antibodies titers against type II collagen, the major cartilage collagen, proposing that the pathogenesis of otosclerosis is related to cartilaginous remnants contained in the otic capsule. Other collagens like type IX and XI, namely "Minor cartilage collagens", appear to be restricted to cartilaginous tissue. The aim of this study was to test otosclerosis patients for the presence of antibodies to these minor collagens using enzyme-linked immunosorbent assays. Levels of antibodies to collagens type II, IX and XI were higher in these patients as compared to sex- and age-matched control subjects, while no differences were found between the levels of antibodies to collagens type I, III, VI and XI. These observations for the first time document the presence of autoantibodies against a minor collagens in patients with otosclerosis and support a possible role for collagen autoimmunity in the etiopathogenesis of otosclerosis. PMID- 8217270 TI - [Hemilaryngectomy of the supracricoid: experience of 58 cases. (Follow-up study for 5 years)]. AB - In the supracricoid hemilaryngectomy the wing of the thyroid and its internally related structures are resected. This is widely used in T2 glottic tumour. Some writers describe its use in limited ventricularis lesions. We have frequently used this technique in both types of lesions. In this paper 58 cases of patients operated on between 1974 and 1986 are reviewed, giving a follow-up period of more than five years. The results obtained, both oncological and functional, are good enough to make this technique basic in the treatment of laryngeal cancer. PMID- 8217271 TI - [Reconstructive laryngectomy. Review]. AB - The AA. review the history, indications, and the surgical technique of the subtotal reconstructive laryngectomy with crico-hyoide-epiglottopexy, that permits natural breathing and voice maintenance. It is an easy operation, indicated for glottic tumours, that gives good oncologic and functional results. It is recommended that loco-regional and general indications be strictly followed. It is enclosed the results of the 25 patients operated in a total time of 5 years. PMID- 8217272 TI - [The use and the potential of auditory electrophysiology in patients in posttraumatic coma]. AB - 21 patients in post-traumatic coma status were submitted to a auditory electrophysiological valuation together with EEG, TC, and "Glasgow Coma Scale" (GCS) with the purpose to obtain the relative prognostic value quoad vitam and quoad valetudinem. In particular it was carried out the brainstem auditory evoked potentials (ABR) and the auditory middle latency potentials (MLR and SSR-40 Hz). 12 patients survived and their clinical conditions were classified according to the "Glasgow Outcome Scale"; 9 of 21 patients died. With the aim of quoad vitam prognosis, the ABR showed a good reliability whereas GCS, EEG, TC and MLR proved not much usefulness. On the contrary the absence of SSR-40 Hz always coincided with the subsequent patients death. With the aim of GOS a meaningful relationship was found between the clinical outcome conditions from coma and the improvement in MLR and EEG. PMID- 8217273 TI - [Primary ciliary dyskinesia: functional and morphological study]. AB - We present 7 patients with a typical symptomatology of immotile cilia syndrome, three of them with complete situs inversus. Nasal mucociliary transport was studied by sero-albumin marked with technetium 99m. In all cases there was an absence of transport. The ultrastructure of the nasal cilia was studied. The findings were: In four cases alterations in the dynein arms, in three cases alterations in the central and peripheral microtubules associated por not to the defects in the dynein arms, and in one cases absence of cilia were observed. The ciliary complexes were common to all cases. PMID- 8217274 TI - [Thymus gland cervical cysts]. AB - We present a cervical thymic cyst clinically manifest as a lateral neck mass and studied preoperatively with ultrasound. We point to the sonographic findings that allow us to include the cervical thymic cyst as one of the diagnostic possibilities. PMID- 8217275 TI - [Spindle cell carcinoma of the larynx]. AB - A spindle cell carcinoma is a rare variant of squamous cell carcinoma often presenting as a polypoid or fungating neoplasm and characterized histologically by a biphasic pattern with foci of conventional in situ or invasive squamous cell carcinoma and a fusiform cell population with a sarcomatous appearance. Most tumors of this type appear in the head and neck areas and particularly in the larynx. We have treated seven laryngeal spindle cell carcinomas in the last ten years. The object of this article is to refer their clinical presentation, biological course, histological findings, and results of treatment. PMID- 8217276 TI - [Subglottal stenosis as the initial manifestation in Wegener's disease]. AB - A 21-year-old man with 3-month history of hoarseness and dyspnea was suspected to have Wegener's granulomatosis with initially appearing in the trachea. In spite of unspecific biopsies, the clinicopathological picture and the high titles of anticytoplasmic autoantibodies (ACPA) confirmed the diagnosis. The early treatment with cyclophosphamide impeded the evolution to graver systemic forms of the disease. PMID- 8217277 TI - [Cyst in the second branchial cleft: review of 3 cases]. AB - Three cases of cysts arising from the second branchial cleft are described. They were completely removed. Histopathological examination revealed that cysts were lined with columnar (respiratory type) epithelium. The authors take this opportunity to review the underlying pathogenic mechanism, the clinical manifestations and therapeutic procedures. PMID- 8217278 TI - [Sudden bilateral deafness of luetic origin in an HIV-positive patient]. AB - We present the clinical record of a positive HIV woman that presented with bilateral sudden hearing loss as a sign of neurosyphilis. We discuss the epidemiological, clinical, diagnostic, and therapeutic implications of positive HIV in syphilis. PMID- 8217279 TI - [Endobronchial hamartoma: a case report]. AB - We described a case of endobronchial hamartoma diagnosed in a seven years-old child (which presented with chronic cough as the only symptom). The chest radiographs showed left lung global condensation. We did rigid bronchoscopy to discard a bronchial foreign body and confirmed the existence of a white-yellowish colour, smooth surface mass obliterating the left main bronchus. Biopsy and anatomopathology study give the result of hamartoma. We performed thoracotomy, bronchotomy and enucleation of the mass. The frequency, clinic, diagnosis and treatment of endobronchial hamartoma are analyzed. PMID- 8217280 TI - [The role of prostaglandins in the inflammation and immunity of human palatine tonsils]. AB - It is well known that prostaglanding are biological mediators which are closely related to inflammation and immunity. To explore the role of PGE2 and PGF2 alpha in inflammation and immunity of human palatine tonsils, the levels of PGE2 and PGF2 alpha in diseased tonsils from 62 patients were measured. It is suggested that PGE2 and PGF2 alpha are present in the tonsillar tissue as inflammatory mediators. The levels of PGE2 and PGF2 alpha may be regarded as the major indicators of activation in chronic tonsillitis and represent the immunologic function of the palatine tonsils to a certain degree. The impairment of the ability of immunologic response in tonsils by inflammation may be related to PGE2. The more severe the inflammation, the more hazardous to the local immunologic defence of tonsils is. It is possible that PGE2 plays an important role in this respect. PMID- 8217281 TI - [Suramin activity in human head and neck squamous cell carcinoma cell lines]. AB - Suramin, a drug used for the treatment of African trypanosomiasis and onchoceriasis, has potential anti-cancer activity. As to the mechanism of action, it is considered to interfere with the action of tumor growth factor and specific growth enzymes. In the present study, the effect of suramin on proliferation of human head and neck squamous cell carcinoma cells was determined. A significant growth inhibition in all three cell lines tested was observed when the concentration of suramin was 100 micrograms/ml or more. The hypothesis was tested to ascertain whether growth inhibition may be due to selective interference with the action of epidermal growth factor. Suramin at growth inhibiting concentrations only partly antagonized the growth stimulating effect of EGF indicating that other mechanisms of action may also contribute to the growth inhibitory activity of suramin. Furthermore, evidence was found that serum proteins other than growth factors presented in the culture medium have a growth stimulating effect on cells and a strongly antagonistical effect on suramin activity. PMID- 8217282 TI - [Effect of estrogen on the experimental nasal hypersensitive reaction]. AB - The nasal hypersensitivity model was established by nasal application of toluene diisocyanate (TDI) in guinea pigs with different levels of estrogen. It was found that high level estradiol may facilitate the development of nasal hypersensitive reaction, and drop of the estrogen level resulted from ovariectomies may postpone it with improvement of the nasal symptoms. It is suggested that the estrogen plays an important role in the pathogenesis of nasal hypersensitive reactions. PMID- 8217283 TI - [Quick immunotherapy for pollinosis]. AB - A preliminary analysis of 47 cases of pollinosis undergone rush immunotherapy revealed that such a protocol not only greatly shortened the time-course of treatment, but also diminished the number of injections required to reach the maintenance dose significantly, thus provided a better compliance of treatment. A two-year observation showed an effective rate of 91.3%. Adverse reactions though occurred, in no case was the reaction strong enough that a discontinuation of the treatment was warranted. The present status of rush immunotherapy has been reviewed and discussed also. PMID- 8217284 TI - [Study on basophil releasability induced by anti-IgE in allergic rhinitis]. AB - We have investigated the basophil releasability induced by anti-IgE in allergic rhinitis patients and normal subjects by reverse human basophil degranulation tests. The results showed that anti-IgE-mediated basophil releasability and total serum IgE were significantly higher in allergic rhinitis patients than that in normal subjects. However, anti-IgE-mediated basophil releasability, total serum IgE and blood eosinophil count were not closely correlated with each other. PMID- 8217285 TI - [Variations of the stereociliary bundles of the outer hair cells in guinea pigs. A scanning electron microscopic study]. AB - Variations of the stereociliary bundles of the outer hair cells in guinea pigs observed under scanning electron-microscope were reported. Changes including transposition and distorted outlines of the stereociliary bundles were distributed in all turns of the cochlear duct and all rows of the outer hair cells, but not in inner hair cells. The possible pathogenetic significance of the changes was discussed. PMID- 8217286 TI - [Effects of transtympanic lidocaine infusion on cochleas]. AB - To investigate into the effects of transtympanic lidocaine infusion on the cochlea, 112 albino guinea pigs were studied by measuring CAP and examining the organ of Corti under optical and electronic microscopes. The changes included prolongation of CAP latency and elevation of threshold microscopeically, the lost OHC-SC of the organ of Corti near the round window. The severity varied with concentrations of lidocaine used. Changes of IHC-SC were slight. Under TEM, the significant changes were that the efferent synaptic spaces were widened and post synaptic cisternae dilated, the mitochondria in OHC, IHC and their nerve endings became swelled and degenerated. The higher the concentration of lidocaine used, the more obvious the morphological damages were. The damages seemed to develop in 14 days. PMID- 8217287 TI - [Image analysis of arterial vessels of the internal auditory meatus during presenile and aged with hypertension and atherosclerosis]. AB - The image analysis of the arterial vessels of the internal auditory meatus in patients with atherosclerosis and hypertension during presenility and presbycusis was done. The inner and outer diameters of the blood vessels in these patients reduced more markedly than those in the controls. There was a negative correlation between the vessel diameter and correlation age. The lumen of the vessels reduced more in patients with atherosclerosis and hypertension than those patients without these conditions. The tunica adventitia showed fibroid thickness. It suggests that the progress of the vessel changes in patients with presbycusis might be accelerated by atherosclerosis and hypertension. PMID- 8217288 TI - [Clinicopathological analysis of midline peripheral T-cell lymphoma]. AB - Sixty-one cases of midline peripheral T-cell lymphoma (MPTL) are reported. All were proven by immunohistochemical staining: UCHL-1 (pan-T cell marker) was positive in 93.4%, L26 (pan-B cell marker) MAC 387 and Lyso were all negative. MPTL were more frequently seen in the nasal cavity than in the palate and larynx, the ratio of male to female was 3.62:1, mean age 38.6 years. According to morpho logical characteristics, two types could be distinguished: monomorphic (14 cases) and polymorphic (47 cases), with different 5-year survival rates. Those with small-medium ALC and convoluted nuclei had a better prognosis. PMID- 8217289 TI - [The isolation of vestibular hair cells in guinea pig crista ampullaris]. AB - Young guinea pigs (250-300 g) were rapidly decapitated and the temporal bones were immediately removed. Under dissecting microscope, the crista ampullaris was removed and incubated in Hank's balanced salt solution containing 0.125 mg/ml collagenase (Sigma IV) at 37 degrees C for 50-60 min. After mechanical dissociation, the isolated cells were transferred onto the coverslips coated with poly-lysine. The cells were left 10-15 min to settle down on the coverslips. Afterward, the collagenase containing solution was replaced by Hank's solution. Observations were made under converted phase-contrast microscope. The results were as follows: 1. Vestibular hair cells are classified into two types. Type I cell was flask-shaped with sensory hairs, a cuticular plate, a long neck and a round bottom containing a large nucleus. The length of type I cell was 18.10 +/- 2.05 microns (mean +/- s n = 32). Type II cells were round shaped or cylindrically shaped without neck but with sensory hairs, a cuticular plate. The longitudinal axis of cylindrically shaped cell was 14.00 +/- 3.16 microns and horizontal axis 9.88 +/- 2.01 microns (mean +/- s n = 29). The diameter of the round cell was 10.31 +/- 1.98 microns (mean +/- s n = 10). 2. The proportion of type I and type II cells was 61/39. 3. An average of 500-700 vestibular hair cells were obtained from each ampulla. 4. Generally, vestibular hair cells could live in Hank's solution for 7-8 hours. The earliest sign of viability degression was the appearance of granules in the cytoplasm. PMID- 8217290 TI - [Development of intercellular junction in the human vestibular receptors. A freeze-fracture study]. AB - The intercellular junctions, especially the tight junctions of the inner ear end organs are considered to act as a barrier to maintain gradients of ions between the endolymph and the perilymph. Thus, the intercellular junctions are of great importance for the function of the inner ear. We have studied the development of intercellular junctions in vestibular end-organs in order to establish a morphological basis for better understandings of the key stage of the development of vestibular end-organs. In the present article, the development and maturation of intercellular junctions in human vestibular receptors were observed with freeze-fracture technique. Junctional complex was already present during 8 weeks of gestation. During 8-11 weeks, a rapid development was seen in the intercellular junctions, so that this period seemed to be the key stage in the development and maturation of intercellular junctions. By the end of 11 weeks, the intercellular junctions had possessed the mature appearance as those seen in adults. PMID- 8217291 TI - [Electron-microscopic study of the vestibular dark and wall cells]. AB - The ultrastructure of the dark cells and wall cells in the vestibular apparatus of the healthy guinea pigs (21 ears) and disordered guinea pigs (12 ears) were observed using transmission electron microscopy. The results showed that otoconia were absorbed mainly by the dark cells, secondly the wall cells. A non-cellular substance was found on the surface of the dark and wall cells and in the endolymphatic space. Probably this substance is related to the absorption of otoconia, particularly the disordered otoconia. PMID- 8217292 TI - [Vertigo caused by vertebrobasilar insufficiency]. AB - This paper deals with electronystagmographic changes in 81 patients suffered from recurrent vertigo considered to be caused by vertebro-basilar insufficiency. Electro-oculogram features showed that (1) In saccadic test, the latency prolonged, the peak velocity of larger amplitude decreased; (2) When the eye smooth pursuit system was tested, Benitez III Type curves appeared in 40% of patients, simultaneously digital computer showed that the total harmonic distortion was more than 15% in 41.9% of patients; (3) the velocity ratio of fast to slow phases of the optokinetic nystagmus decreased, as a result of decrease in fast phase velocity. (4) The spontaneous and positional nystagmus occurred in 58% of patients. (5) The intensity of caloric response was weaker than that in normal subjects, canal paresis increased, failure of fixation suppression occurred in 17.7% of patients. PMID- 8217293 TI - [Sinusoidal harmonic acceleration test in normal Chinese and 400 dizzy patients]. AB - Forty healthy youth, 20 aged Chinese volunteers and 400 dizzy patients were tested with SHAT at frequencies of 0.01-0.64Hz. The peak velocity was 50 degrees/s. The commonly used three parameters: phase, gain, asymmetry were calculated by computer. Alertness tests in the darkness demonstrated a gain increase and a decrease of phase lead with increasing frequency. The bilateral responses were symmetrical in normal volunteers. The asymmetry value was in the limit of 5 degrees. The values of all the parameters made no sexual difference. The phase value with 0.01Hz in the aged volunteers was a little smaller than that in the younger volunteers. An abnormal result was found in 204 patients (51%). Phase lag decreases were the most common abnormal results. Both patients with Meniere's disease and with central disorders revealed phase lag decreases. However, patients with central lesions showed decreases of phase lag in more frequencies. Direction of asymmetry in patients with central lesion was in good correlation with the side of lesions. The five common types of abnormality were reported in the present paper, they were vestibular habituation and asymmetry, vestibular habituation, vestibular asymmetry in higher frequencies, vestibular deficit and vestibular hyperreactivity. PMID- 8217294 TI - [The effect of streptomycin on energy metabolism in inner ear tissues in guinea pigs]. AB - Fifty-four guinea pigs were divided into three groups. Group I was injected with streptomycin sulfate 200 mg/kg body wt.ip. for 8 days; group II was injected with streptomycin sulfate 200 mg/kg body wt. and Chinese angelica 2 ml/kg body wt. ip. for 8 days; group III, serving as control, was injected with corresponding volume of water for injection. Glucose and pyruvate levels were determined chemically, ATP, ADP and AMP were determined by HPLC. The hearing reflex thresholds were measured before injection of drug and sacrifice. The glucose content in inner ear tissues of group I and II was found to be lower than that of the control. The pyruvate content in group I and II was higher than that of the control. The ratio of pyruvate to glucose in the group I and II was significantly higher than that of the control, P < 0.05. ATP level in inner ear tissues in group I (50.3 +/- 39.0 micrograms/mg protein) decreased significantly as compared with the control (167.7 +/- 115.4 micrograms/mg protein), P < 0.05, but not in group II (151.6 +/- 124.3 micrograms/mg protein). The energy change in each group was in the range of 0.80-0.84. The hearing reflex threshold attenuation in group I 8 days after injection of drug was slightly lower than that prior to the injection of the drug. The results suggest that streptomycin might inhibit the uptake and metabolism of glucose and decrease the ATP level in the inner ear tissues, and that the inner ear tissues accelerate the metabolism of amino-acids for compensation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217295 TI - [Colored biomicrospheres for studies of cochlear microcirculation]. AB - For many years in our laboratory, toads red blood cells have been used as biomicrospheres for study of cochlear microcirculation. In the present experiments the cochlear blood flows (CBF) was twice determined in the same animal by using colored biomicrospheres. The red blood cells were stained separately with eosin and azure blue. The biomicrospheres of two different colors were injected intracardially in the same guinea pig at two different times with an interval of 4 min. The CBF were detected by using a laser Doppler system simultaneously. The finding showed that color of red and blue biomicrospheres were contrast sharply, they were all distinguished easily from the surrounding tissue. The adequate number of microspheres injected each time was 9 x 10(6)/ml. The results of CBF were not different between the first and second injection. PMID- 8217296 TI - [The effect of superior cervical sympathetic ganglionectomy on cochlear blood flow in guinea pigs]. AB - The effect of superior cervical sympathetic ganglionectomy on cochlear blood flow (CoBF) was observed in 21 guinea pigs. The CoBF was measured with Laser Doppler Flowmeter. The systemic blood pressure (BP) was simultaneously recorded. The elevation of BP as well as the increase in CoBF following ganglionectomy were not statistically significant; the change in CoBF was somewhat consistent with the variation of BP. The results imply that there is no significant effect of superior cervical sympathetic ganglionectomy on CoBF of guinea pigs. PMID- 8217297 TI - [Stapedial reflex test for gerontal sensorineural hearing loss]. AB - The purpose of this investigation was to find a method that can diagnose sensorineural hearing loss early. Fifty subjects, aged more than 60 years, with hearing level ranged from normal to profound deafness, were examined. The noise tone difference (NTD) were calculated at 0.5, 1, 2, and 4kHz from these data. The results indicated that NTD at 1kHz was more sensitive than others for diagnosing gerontal sensorineural hearing loss in early stage. PMID- 8217298 TI - [A long-term observation on cystic hypophysoma and craniopharyngioma treated by colloidal 32P transnasosphenoid injection]. AB - Six patients suffering from cystic hypophysoma and one from craniopharyngioma treated with intracavitary radiation by colloidal 32P transnasophenoid injection were studied. After injection, the headache was eliminated and vision improved in all cases, visual field enlarged in 4, and sexuality improved in 5 male cases. All the patients recovered their normal daily life and work in 2-12 year's follow up period. The conclusion is that the above mentioned therapy is simple, safe and effective. PMID- 8217299 TI - [Study on plasma levels of vasoactive intestinal peptide (VIP) in patients with allergic rhinitis]. AB - The plasma levels of vasoactive intestinal peptide (VIP) were measured in 33 allergic rhinitis patients and 21 controls by means of supersensitive and highly specific VIP-radioimmunoassays. At the same time the blood flow was observed by using the laser-Doppler flowmetry. The result showed that the levels of plasma VIP in patients with allergic rhinitis were higher than those in the control group (54.93 +/- 30.58 ng/L, 25.97 +/- 11.83 ng/L, P < 0.01). The levels of plasma VIP related significantly to the volume of blood flow in nasal mucosa (gamma = 0.7678, P < 0.001). It is concluded that VIP could induce vasodilation in nasal mucosa, leading to an increase in nasal mucosa blood flow. PMID- 8217300 TI - [A study of T-lymphocyte subsets, IL-2 production and IL-2 receptor expression in peripheral blood lymphocytes in patients with nasopharyngeal carcinoma]. AB - T lymphocyte subsets, IL-2 production and IL-2 receptor expression were detected in PBLs of 31 NPC patients and 28 normal subjects and of normal PBLs populations under the influence of serum of NPC patients. The results were as follows: CD4+ and IL-2 receptor expression, CD4+:CD8+ ratios and IL-2 production were significantly depressed and CD8+-significantly elevated in PBLs of NPC patients before radiation and of normal PBLs populations under the influence of the serum of NPC patients. CD8+ was significantly decreased and CD4+, IL-2 production and IL-2 receptor expression were depressed in patients after radiation. These suggest that cellular immunity and immunoregulation are impaired in NPC patients before and after radiation. PMID- 8217301 TI - [A comparison of the therapeutic effect between preoperative radiotherapy plus operation and operation alone for laryngocarcinoma. A prospective study of 260 cases]. AB - A prospective study on the therapeutic effect of either preoperative radiotherapy and operation (101 cases) or operation alone (159 cases) by random grouping for a total of 260 patients with laryngocarcinoma were conducted. By analysing the survival curve and time schedule test, we compared the population survival rate, clinical typing, T classification, staging, pathological grading, operative method and infection rate between the two groups. The result shows that there is no significant difference between survival curves. It is indicated that the preoperative radiotherapy can increase neither the five-year survival rate nor the postoperative infection rate evidently, but it may increase the survival rates of those with poorly differentiated squamous carcinoma (grade III or IV), those in advanced stage carcinoma (T3 or T4 stage IV) or those who will undergo extensive laryngectomy. The three-year and five-year survival rates were 75.4% and 67.5% respectively; for the glottic type the rates were 78.4% and 71.0%; 73.7% and 64.5% for the supraglottic type; 76.1% and 72.3% for the partial laryngectomy; and 71.4% and 53.9% for the total laryngectomy. PMID- 8217302 TI - Methods for finding genes. A major rate-limiting step in positional cloning. AB - Identification of transcribed sequences from within genomic regions has been a major rate-limiting step in the pursuit of genes involved in many human genetic diseases. Early efforts focused primarily on screening of cDNA libraries, identification of evolutionarily conserved sequences, and northern blot hybridization. In recent years, several innovative techniques for gene identification have been devised. These techniques expand the size of the genomic region capable of being scanned for genes, while also allowing detection of genes regardless of their expression patterns. This article reviews several new and older techniques and discusses the advantages and limitations of each. PMID- 8217303 TI - "Junction trapping". A simple PCR-based method for the isolation of YAC-insert termini. AB - A new and potentially reliable method for the isolation of yeast artificial chromosome (YAC)-insert termini, termed junction trapping, is described. This method is based on simple partial digestions of the YAC-containing yeast strain, ligation to a plasmid vector, and selection of the termini by two rounds of polymerase chain reaction (PCR). To date, the method has generated both terminal sequences from each of nine YACs (100%) that have been examined. PMID- 8217304 TI - Comprehensive restriction enzyme lists to update any DNA sequence computer program. AB - Restriction enzyme lists are presented for the practical working geneticist to update any DNA computer program. These lists combine formerly scattered information and contain all presently known restriction enzymes with a unique recognition sequence, a cut site, or methylation (in)sensitivity. The lists are in the shortest possible form to also be functional with small DNA computer programs, and will produce clear restriction maps without any redundancy or loss of information. The lists discern between commercial and noncommercial enzymes, and prototype enzymes and different isoschizomers are cross-referenced. Differences in general methylation sensitivities and (in)sensitivities against Dam and Dcm methylases of Escherichia coli are indicated. Commercial methylases and intron-encoded endonucleases are included. An address list is presented to contact commercial suppliers. The lists are constantly updated and available in electronic form as pure US ASCII files, and in formats for the DNA computer programs DNA-Strider for Apple Macintosh, and DNAsis for IBM personal computers or compatibles via e-mail from the internet address: NETSERV@EMBL-HEIDELBERG.DE by sending only the message HELP RELIBRARY. PMID- 8217305 TI - Incorporation of nonbase residues into synthetic oligonucleotides and their use in the PCR. AB - Oligonucleotides containing the nonbase residues 1,3-propanediol or 1,4-anhydro-2 deoxy-D-ribitol were synthesized and used as primers for the polymerase chain reaction (PCR). Since these residues cannot be replicated by a DNA polymerase, the resulting PCR products have protruding 5' ends. Primers were designed with three regions, a 3' region complementary to the desired template, a 5' region complementary to a preselected nucleotide sequence, and a nonreplicable element interposed between these two containing 1-3 of the nonbase residues. The primers were used in a PCR and the products hybridized without denaturation to a solid support containing an immobilized preselected nucleotide sequence. Studies are reported showing the effects of the nonreplicable elements in primer extension reactions and the application to the capture of PCR products. PMID- 8217306 TI - [The late results in the surgical treatment of patients with arteriosclerosis obliterans of the arteries of the lower extremities]. AB - Long-term outcomes of surgical treatment were examined in 157 patients with atherosclerosis obliterans of lower extremity arteries. Complications of an atherosclerotic process are a basic cause of death in the patients in the long term postoperative period. More than half (53.7%) the deaths were due to coronary heart disease. In a group of patients in whom coronary heart disease was not diagnosed prior to surgery, death from myocardial infarction was observed in 20.4% of cases during 5 years. Hypokinetic hemodynamics is a poor predictor of survival of patients with lower extremity artery atherosclerotic occlusions. PMID- 8217307 TI - [The percutaneous transluminal balloon valvuloplasty of valvular stenosis of the pulmonary artery in treating tetralogy of Fallot as an alternative to the surgery of applying a systemic-pulmonary anastomosis]. AB - From January 1991 to May 1992 transluminal balloon valvuloplasty [correction of vulvoplasty] of severe valvular stenosis of the pulmonary artery was performed in 14 patients with Fallot's tetrad at the Institute of Cardiovascular Surgery named after A. N. Bakulev. Five of them had pulmonary artery hypoplasia, 2 had stenosis and hypofunction of the systemic-pulmonary anastomosis applied by the Blalock Taussig, which made them perform balloon angioplasty of the narrowed distal portion of the anastomosis. The patients' age ranged from 11 months to 14 years (mean age 6.8 +/- 1.1 years). Arterial blood oxygen saturation varied from 51 to 72% (mean 69.2 +/- 2.4%). The diameter of a valvular ring was 8-13 mm. The diameter of a balloon catheter exceeded that of the valvular ring by 20-25%. After dilation, arterial blood oxygen saturation increased from 69.86 +/- 2.5 to 85.1 +/- 1.2%. The angiometry performed after pulmonary artery valvuloplasty in patients with pulmonary hypoplasia showed an increase in sizes of all pulmonary arterial segments on an average by 22.5 +/- 4.1%. Later on 5 patients were radically operated on. Thus, with the ultimate goal of preparation of patients with severe Fallot's tetrad for radical surgery, transluminal balloon valvuloplasty in some patients with severe valvular stenosis of the pulmonary artery may be alternative to a systemic-pulmonary anastomosing operation. PMID- 8217308 TI - [Permanent endocardiac electrical stimulation by a puncture technic (methodological recommendations)]. PMID- 8217309 TI - [The clinical picture, diagnosis and surgical treatment of the "scimitar syndrome"]. AB - Four patients with the scimitar [correction of yataghan] syndrome underwent examinations and surgical management. The syndrome includes abnormal drain of the right pulmonary vein into the vena cava inferior, abnormality of the right lung, right displacement of the heart and right pulmonary hypoplasia. Three patients were diagnosed as having the scimitar [correction of yataghan] syndrome during examinations and the defect was found in 1 patients during surgery. Cardiac catheterization with selective angiopulmonography is one of the most informative diagnostic techniques. The methods of choice in surgical management involve direct reimplantation of the abnormal pulmonary vein into the left or right atrium, followed by transfer of its ostium into the left atrium. PMID- 8217310 TI - [Our initial experience of protecting the myocardium by irrigating the pericardial cavity with a circulating cold solution during operations with artificial circulation]. AB - In 21 patients with coronary heart disease, a procedure of protecting the myocardium was used during cardiac surgeries via irrigation of the pericardial cavity with circulating cold solution in combination with cardioplegia into the aortic root. The application of the procedure maintained stable myocardial temperature from 10.26 +/- 1.55 to 11.99 +/- 1.95 degrees C, excluding excessive overcooling and premature warming. The procedure awaits further studies in terms of biochemical changes and morphology of the myocardium at various stages of surgery. PMID- 8217311 TI - [Clinical and ultrasonic validation for the intracavernous use of papaverin hydrochloride for the test screening of patients with arterial erectile impotence]. AB - Intracavernous administration of 2% papaverine hydrochloride solution, 4 ml, was conducted in 25 patients with various arterial erectile impotence and 25 patients with psychogenic impotence. The efficiency of the solution was judged from clinical findings and results of penile blood flow estimation via ultrasonic Doppler graphy 10 minutes after injection. Ultrasonic Doppler graphy involved calculation of the pulse wave acceleration measure and penile-brachial index of acceleration. In patients with psychogenic impotence the penile blood flow after intracavernous papaverine hydrochloride assumed the features of great blood flow, whereas it remained reduced in patients with arterial erectile impotence. In Doppler sonography, basic parameters were determined, viz assessment of the form of a Doppler wave, initial blood flow velocity, maximum blood flow velocity and their difference. PMID- 8217312 TI - [The late results of mitral valve prosthetic replacement in patients with acquired heart defects using biological, ball and disk prostheses]. PMID- 8217313 TI - [The procedure for percutaneous endovascular angioplasty in multiple occlusive stenotic lesions of the arteries of the pelvis and lower extremities]. AB - The authors consider the tactical features of transcutaneous endovascular angioplasty in 110 patients with multiple arterial occlusive and stenotic lesions of the pelvis and lower extremities. A total of 299 arteries were operated on and desobliteration of stenoses and occlusions were performed. Five procedures of transcutaneous endovascular angioplasty: via transfemoral antegrade, transfemoral retrograde, transfemoral contralateral, transpopliteal, and transaxillary accesses were used alone or in combination. The tactics of transcutaneous endovascular angioplasty was determined by the nature, site, and extent of lesions, as well as the status of the distal arterial bed. Clinical positive results of transcutaneous endovascular angioplasty were obtained in 94 (85.4%) patients. Complications following endovascular interventions were encountered in 5 (4.6%) cases. PMID- 8217314 TI - [The surgical treatment and prevention of rethromboses in acute ileofemoral venous thromboses]. AB - The paper outlines the results of surgical management of acute ileofemoral venous thrombosis in 44 patients. In 23 patients from Group 1 venous thrombectomy was performed by the femoral access, in 21 patients from Group 2, by intraperitoneal pararectal access. For prevention of rethromboses in the postoperative period, in Group 2 continuous regional infusion of a rheopolyglucine-streptokinase-heparin mixture with concomitant administration of the mixture into the paravasal fat of a diseased segment was made. Good results were obtained in 76.2%. PMID- 8217315 TI - [Methods for the curative treatment of pleural empyema with bronchial fistulae in patients with pulmonary tuberculosis]. AB - In contrast to non-specific pleural empyemas in which closed sanitization is sufficiently beneficial, an early application of thoracostoma is essential for patients with tuberculous pleural empyema with bronchial fistulas. Thoracostoma allows for effective sanitization of the cavity, long-term antituberculous chemotherapy and preparation of patients for radical operations. This has been supported by the comparative analysis of the outcomes of radical operations in 139 patients following closed and open management of the empyemic cavity in pulmonary tuberculosis. The site of thoracostoma is defined depending on the location and volume of an abscess and the forthcoming radical operation. Long acting antiseptic dressings containing chlorohexidine bigluconate, which are based on the polymer polyhydroxyethyl methacrylate and which have been developed in the clinical setting, and ultraviolet irradiation with a unique-design apparatus are proposed for sanitization of open pleural empyemas. PMID- 8217316 TI - [Intrapulmonary instillations in destructive tuberculosis]. AB - Destructive tuberculoses were treated with intrapulmonary instillations at the Phthisiosurgical Unit of the Kostroma Regional Tuberculosis Dispensary from January 1, 1985, to December 31, 1991. 5% saluside solution (15.0 ml) and 10% tubaside solution (6.0 ml) were used. The major indication for treatment with this method was a process of pulmonary decay. An operation was made in 64 patients after instillations. With instillations, the decay cavity was closed in 32.9% of cases, but with their combination with surgery it was closed in 50% of cases. Among primary patients, these figures were 42.4 and 66.2%, respectively. PMID- 8217317 TI - [The use of an antibacterial adhesive agent for the provision of an airtight seal and obliteration of the pleural cavity in spontaneous pneumothorax]. AB - The authors described a procedure for pleurodesis with a new plasma antibacterial glue in the surgical treatment of bullous lung disease complicated with spontaneous pneumothorax. A total of 28 patients were operated on. In 17 cases the glue was used for pleurodesis. The follow-up period was up to 1.5 years. No relapses of spontaneous pneumothorax were observed. No complications due to glue use were noted. Pleurodesis was evidenced by chest sonography from the absence of visceral pleural motion against parietal one. PMID- 8217318 TI - [The conservative treatment of stable encapsulated pleural empyema in children]. AB - The author analyzed the results of treating 20 patients with stable loculated pleural empyemas. The treatment involved punctures and lavage of the cavity and efforts to recover bronchial patency and alveolar ventilation. In all patients, the residual cavity was liquidated and the lung got smoothed completely. PMID- 8217319 TI - [The extracorporeal correction of disorders in the blood aggregate state in patients with acute infectious destructions of the lungs and pleura]. AB - Positive hemorheological effect was found in using therapeutical plasmapheresis in combination with extracorporeal blood oxygenation. Indications and contraindications for therapeutical plasmapheresis are discussed in the paper. PMID- 8217320 TI - [The complement system in assessing the reserve potentials of the immune system in patients with nonspecific lung diseases]. AB - The complement system was studied in 42 patients with various unspecific pulmonary diseases. It was established that the rate of complement system activation depends on the acuteness of the course of the pyo-inflammatory process in the lungs. The results of study of the kinetics of complement system activation make it possible to prognosticate the course and outcome of inflammatory pulmonary diseases and identify a risk group of patients with diminished reserve possibilities of the immune system and prescribe immunocorrective therapy opportunely. PMID- 8217321 TI - [The development of late dysphagia after the implantation of an antireflux prosthesis]. AB - The paper analyzes three cases of developed uniphagia and/or dysphagia in long term postoperative periods. No predictors of late dysphagia were observed. Maintenance of antireflux activity after prosthesis removal is of great interest. The authors recommend that the antireflux prosthesis should be used in the situations at a high risk of routine fundoplication. PMID- 8217322 TI - [The restoration of esophageal patency in cicatricial strictures by using magnetic elements]. AB - The authors present their clinical experience (4 observations) with magnetic devices for application of the esophageal anastomosis and removal of its scarring strictures in an area of anastomosis application. They also describe the procedures for introducing the magnetic elements to the site of anastomosis with fiberscopes. The procedure allowed traumatic surgery to be avoided and a stable positive result to be achieved. PMID- 8217323 TI - [Methods of blood autotransfusions in thoracic surgery (a review of the literature and the authors' own cases)]. PMID- 8217324 TI - [A traumatic aortocaval aneurysm]. PMID- 8217325 TI - [The correction of a mixed form of partial anomalous drainage of the pulmonary veins with a supernumerary (left) vena cava superior draining into the coronary sinus]. PMID- 8217326 TI - [A 2-stage anatomical correction of simple transposition of the great vessels in a nursing infant]. PMID- 8217327 TI - [The efficacy of the combined conservative therapy of patients with chronic obliterating arterial diseases of the extremities in outpatient practice]. AB - The paper provides the results of multimodality conservative therapy in 527 patients with chronic obliterating diseases of extremity arteries, which was performed in the outpatient setting. Factors influencing its efficiency were analyzed. The paper emphasizes the value of this direction of treatment whose underestimation sharply aggravates the prognosis of these diseases, including the results of their surgical management. Having obtained positive results in 84.5% of patients, the authors note the efficiency of treatment to be decreased with severe arterial insufficiency of lower extremities (5% of negative results in Stage IIa, 23% in Stage IIb, and 40% in Stage III), in patients with prior surgical interventions, and in elderly patients with atherosclerosis obliterans and younger patients with non-specific aortoarteritis. PMID- 8217328 TI - Pain in children. PMID- 8217329 TI - Patient care outcomes related to management of symptoms. PMID- 8217330 TI - The role of nurse researchers employed in clinical settings. PMID- 8217331 TI - Nurse-midwifery education. PMID- 8217332 TI - AIDS-related knowledge, attitudes, and risk for HIV infection among nurses. PMID- 8217333 TI - Family unit-focused research: 1984-1991. PMID- 8217334 TI - Nursing research on patient falls in health care institutions. PMID- 8217335 TI - Acute confusion in the elderly. PMID- 8217336 TI - The shivering response. PMID- 8217337 TI - Chronic fatigue. PMID- 8217338 TI - Side effects of cancer chemotherapy. PMID- 8217339 TI - HTLV-II among pygmies from Cameroon. PMID- 8217340 TI - HTLV-II seroprevalence in pygmies across Africa since 1970. AB - HTLV-II-specific antibodies, with patterns similar to those in the Americas, were present in sera collected about 1970 from Bambuti pygmies in Zaire (14/102; 14%) and from pygmies in Cameroon (5/214; 2.3%), and were more prevalent than HTLV-I. In the Central African Republic, 504 pygmies were HTLV negative. After finding of 4 HTLV-II seropositives among 12 Bambuti pygmies sampled in 1991, this established that HTLV-II or a related retrovirus is present as an ancient endemic in some, but not all, insulated groups of African pygmies, similar to the HTLV-II distribution in Amerindian populations. The endemic among the oldest inhabitants of central Africa, and the occasional and scattered occurrence of apparent HTLV II among predominant HTLV-I in other Africans, fit well with an ancient African virus and not with importation from the New World. Theories on the origin and evolution of the primate T-lymphotropic viruses (PTLVs) should take into account the longstanding presence of HTLV-II-type viruses in both the Old and New World. Present serology suggests identity of the African viruses with HTLV-II, but their assignment to a new HTLV type is open should genetic analysis show strong divergence from American HTLV-II. Clinical expression, if any, remains to be studied. PMID- 8217341 TI - Large granular lymphocytosis in a patient infected with HTLV-II. AB - HTLV-II has been associated with a variety of lymphoproliferative disorders, including atypical hairy cell leukemia, chronic T cell leukemia, T prolymphocytic leukemia, and large granular lymphocytic leukemia. However, a direct or indirect role for HTLV-II in these disorders is not yet firmly established. We studied a patient diagnosed as having leukemia of the large granular lymphocyte (LGL) type who was HTLV-II seropositive, to determine if the expanded cell population was infected. Two populations of CD3-CD16+ LGL were identified; one was CD8+, the other CD8-. Populations of cells with these surface markers as well as normal CD3+CD4+ and CD3+CD8+ cells were separated by flow cytometric methods, DNA extracted, and gene regions of HTLV-II pol and tax amplified, using the polymerase chain reaction, and probed after Southern blotting. HTLV-II was detected in the CD3+CD8+ population, and not in the CD3-CD16+ large granular lymphocyte population. This finding indicates that the role of HTLV-II, if any, in LGL proliferation is indirect. PMID- 8217342 TI - Nucleotide sequence analysis of human T cell leukemia virus, type II (HTLV-II) isolates. AB - A study by Hall et al. (J Virol 1992;66:2456-2463; Ref. 11) has suggested the existence of two closely related molecular subtypes of HTLV-II, which were tentatively designated HTLV-IIa and HTLV-IIb. To confirm this nucleotide sequence analysis of 986 bp of the env gene region encoding the entire surface glycoprotein, gp46, and the amino terminus of the transmembrane glycoprotein, gp21, of 10 HTLV-II isolates was carried out. The results clearly established the existence of two subtypes and demonstrated a 4.3% divergence in sequence in this region. Analysis of other gene regions of the provirus, including the pol (1544 bp), gag (448 bp), and the entire LTR (743 bp) of two representative isolates of each subtype, showed a sequence divergence of 3.8 to 5.7%, with greatest divergence occurring in the LTR. In addition to single nucleotide changes, the gag regions encoding the structural protein, p19, of the HTLV-IIb isolates were also found to have a 66-bp deletion that would be expected to result in a p19 protein having a 22-amino acid deletion in the carboxy-terminus region. Attempts to exploit this to differentiate the two subtypes serologically were unsuccessful in that recombinant p19 proteins of both subtypes were found to be antigenically cross-reactive. The finding of two molecular subtypes of HTLV-II may have important implications for a better understanding of the biological and pathogenic properties of the virus, and will be useful in characterizing the viruses present in endemic foci in American Indian populations. PMID- 8217343 TI - Potentiation of cytotoxicity of Kaposi's sarcoma related to immunodeficiency syndrome (AIDS) by liposome-encapsulated doxorubicin. AB - Kaposi's sarcoma is an independent criterion for the diagnosis of AIDS and develops in nearly 15% of all cases. Current chemotherapy regimens are associated with substantial toxicity, particularly bone marrow suppression, which limit their long-term use. In an attempt to reduce treatment-related toxicity and enhance uptake of the drug in tumor cells, free and liposome-encapsulated doxorubicin was tested in vitro. The liposomes were prepared with cardiolipin, phosphatidylcholine, and cholesterol. Kaposi's sarcoma (KS)-derived spindle cells were exposed to free doxorubicin (DOX) and liposome-encapsulated doxorubicin (LED) for various time intervals and analyzed for cellular cytotoxicity, thymidine incorporation, and cellular drug uptake. Cytotoxicity studies of KS cells with free DOX and LED showed an IC50 of 288 and 7.5 ng/ml, respectively, hence demonstrating a 38-fold higher cytotoxicity by LED. Thymidine incorporation studies in KS cells demonstrated over one log higher toxicity to LED compared to free DOX. Cellular drug uptake studies showed that free DOX concentration peaked in 1 hr in KS cells whereas LED continued to accumulate up to 4 hr. At 4 hr, anthracycline uptake through LED was fivefold higher than the uptake of free drug. Similarly LED uptake in the cells evaluated by direct fluorescent microscopy was much more intense and more frequent than the uptake of free drug. Thus AIDS-KS cells appear to be exquisitely sensitive to LED, which may provide a higher therapeutic to toxicity index in clinical use. PMID- 8217344 TI - Perturbation of the immunosuppressive action of glucocorticoids in rat thymocytes by liposoluble extracts of serum from AIDS patients. AB - Liposoluble extracts of serum from healthy men and AIDS patients (stages IVC1 and IVD by CDC criteria) inhibited the incorporation of [3H]thymidine into isolated rat thymocytes, but AIDS extracts were less inhibitory, requiring 1.8 times more cortisol in the AIDS extracts than in the healthy extracts to inhibit [3H]thymidine incorporation by 50%. Although the total serum extracts from AIDS patients contained 1.7 times more cortisol than the extracts from healthy controls, the AIDS extracts decreased the binding affinity (Ka) of [3H]dexamethasone to rat thymus glucocorticoid receptors by 50% less than the healthy control extracts. The present study seems to indicate that a substance(s) can be extracted from the serum of AIDS patients that attenuates the inhibitory effect of cortisol on thymocyte proliferation and interferes with the binding of cortisol to the glucocorticoid receptor. PMID- 8217345 TI - A rapid, automated microtiter assay for measuring neutralization of HIV-1. AB - A sensitive, rapid, and quantitative ELISA for p24 is described, which can be used as the read-out to test for HIV-1 neutralization in the syncytium-forming microassay and can replace the counting of syncytia under the microscope. This assay can be used reliably for divergent strains of HIV-1, including those that do not induce syncytia. The new read-out permits evaluation of neutralization at 3 days rather than 5 days. Using this assay, the neutralizing activity of several new and previously described human monoclonal antibodies against HIV-1 was characterized. PMID- 8217346 TI - A peptide substitution in HIV-1 gp120 first hypervariable domain enhances its immunogenicity in mice. AB - The envelope (Env) protein from HIV-1 is the focus of several vaccine trials in humans. It could be considered for the optimization of Env vaccinal preparations to add within the molecule defined epitopes, for instance epitopes conserved among viral isolates from HIV-1, such as from Gag or Nef proteins. As a first step to this approach, we have constructed by in vitro mutagenesis HIV-1(LAI) Env gp120 molecules in which a 12-amino acid sequence in the first (V1) or the third (V3) hypervariable region was substituted by the hemagglutinin (HA) 307-318 peptide from the influenza virus, a dominant T helper cell epitope in humans. The proteins were produced by recombinant vaccinia viruses. They had kept their structural properties in terms of serological recognition and binding to CD4. Of note, we observed that the gp120 protein substituted in the V1 domain elicited a stronger serological immune response in mice compared to native or V3 substituted gp120. This indicates that gp120 can accommodate large substitutions without major structural perturbations and that, on the contrary, some of them could prove beneficial in terms of immunogenicity. PMID- 8217347 TI - Ferritin downregulation in HIV-infected cells. AB - Levels of serum ferritin are increased in AIDS patients in relation to the progression of the disease. To establish whether or not this in vivo increase could be due to a direct effect of the virus on the infected cells, three HIV permissive cell lines, the CD4-positive HeLa-T4-6c and C8166 cells and the CD4 negative RD cells, were infected with HIV-1 strains. The expression of ferritin was followed during the course of acute infection, in parallel to other cellular components. Unexpectedly, all three cell lines showed a phase of decrease in their ferritin content after infection by HIV-1, not justified by the modest and late increase of ferritin in the fluids, due to disruption of infected cells. Since ferritin is involved in the control of cell growth and DNA synthesis, its downregulation may be implied both in cell toxicity and DNA abnormalities due to HIV infection. PMID- 8217348 TI - Lymphoproliferative responses in macaques immunized with inactivated SIV vaccine. PMID- 8217349 TI - Rapid screening for simian immunodeficiency virus variants using single-strand conformation polymorphism of PCR-amplified DNA fragments. PMID- 8217350 TI - Proliferation markers in breast cancer. PMID- 8217351 TI - In vitro assays for antitumour activity: more pitfalls to come? PMID- 8217352 TI - High failure rate of carboplatin-etoposide combination in good risk non seminomatous germ cell tumours. AB - 24 patients with good risk non-seminomatous germ cell tumours (GR-NSGCT) were enrolled in a phase II trial combining carboplatin (C) and etoposide (E). Carboplatin was given at a fixed dose of 450 mg/m2 at d2, and E 120 mg/m2, dl-3, every 4 weeks x 4 cycles (cy). Myelosuppression was the major toxicity with neutropenia grade 4 in 18 cy (19%) and grade 3 in 26 cy (27%). Thrombocytopenia grade 3 and 4 occurred in 7 and 1 cy, respectively. Responses included: 20 complete responses (CR) (83%) with 16 clinical CR and 4 pathological CR; 3 additional patients had complete surgical removal of residual disease (SRRD) with viable tumour (surgical CR); 1 patient progressed during C+E therapy. 5 of the 16 clinical CR relapsed, and all the 3 surgical CR progressed despite post-operative salvage chemotherapy. Adverse events occurred in 9 patients (37.5%; 95% C.I., 19 59%). After a median follow-up of 24 m (range 14 to 38) 4 patients had died [3 progressive disease (PD), 1 suicide while in CR], 3 were alive with PD, and 17 had no evidence of disease. No significant correlation between area under the curve values of carboplatin, overall treatment failure and the platelet nadirs was observed. We conclude that the efficacy of the C+E regimen as given in our protocol is inferior to the standard cisplatin-containing regimens. The low dose density (D/I) of carboplatin could be responsible for the high failure rate. PMID- 8217353 TI - Cell proliferation of breast cancer evaluated by anti-BrdU and anti-Ki-67 antibodies: its prognostic value on short-term recurrences. AB - The prognostic value of breast cancer proliferative activity was evaluated in 385 women operated for primary, non-metastasised mammary carcinoma. Cell kinetics was measured using two immunohistochemical techniques. Cells in S-phase of cell cycle were labelled in vitro by incubation of fresh tissue fragments with 5-bromo 2 deoxyuridine (BrdU), a thymidine analogue. Nuclei of cells in active DNA synthesis were stained by an anti-BrdU monoclonal antibody (Mab). Cells in interphase and mitosis were detected with Ki-67, a Mab that is known to react with a nuclear antigen present in G1/S/G2/M phases of cell cycle, but not in resting cells. This reagent provides a means of evaluating the growth fraction of neoplastic cells. BrdU was incorporated in a proportion of tumour cells ranging from 0.1 to 65.5% (median 6.8%). In the panel of tumours presented in this report the median percentage of Ki-67 positive cells (Ki-67 score) was 9.0% (range 0.1 77%). The relationship between disease-free survival (DFS), BrdU labelling index, Ki-67 score and 13 different clinico-pathological variables was investigated by multivariate analysis, using the Cox proportional hazards model. Axillary node status (P = 0.009) and Ki-67 score (P = 0.038) emerged as independent prognostic factors. Nodal status and tumour growth fraction allowed division of patients into groups at different risk of relapse: tumours with a proliferative index below the median value showed a lower recurrence rate than tumours with a high proliferative activity (P < 0.001). In particular, no relapse occurred in pN0 patients bearing carcinomas with a Ki-67 labelling < 9.0% 4 years after surgery. These findings suggest that the evaluation of proliferative activity in breast cancer enhances the probability of correctly predicting outcome after surgery and could be of assistance in the planning of adjuvant therapies. PMID- 8217355 TI - Risk factors for early mortality in allogeneic bone marrow transplantation. A multivariate analysis on 174 leukaemia patients. AB - Allogeneic bone marrow transplantation in patients with leukaemia is an aggressive therapeutic procedure which implies high early mortality. Current opinion trends attribute the greater part of the procedure toxicity to the preparative regimen. The results of a multivariate analysis on data of 174 leukaemia patients conditioned with total body irradiation (TBI), 10-12 Gy, single dose or fractionated, and lung shielding at 8 Gy, plus chemotherapy: cyclophosphamide 120 mg/kg, before or after TBI, are presented. The variables statistically related with early mortality are age, Karnofsky index (KI) and acute graft-versus-host disease (GvHD). No variable depending on radiotherapy reached the significance level. The relative risk of early mortality for patients older than 26 years, in bad general condition (KI < 90%), or developing acute severe (grades II-IV)GvHD, is 3.99, 5.68, and 6.71, respectively. We conclude that in the range of TBI schedules analysed, radiation therapy is not an important factor in early death, but acute severe GvHD, or recipient's bad general condition are factors to be improved by bone marrow transplantation teams if they want to improve the therapeutic index of the procedure. PMID- 8217354 TI - The influence of adjuvant chemotherapy on outcome after relapse for patients with breast cancer. AB - This study examines the outcome following relapse for 176 patients who had been entered into a randomised trial comparing adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with no adjuvant therapy (controls). Relapse has occurred in 65/144 (45%) of the CMF group and 111/158 (70%) of controls (P < 0.0001). 123/176 patients received endocrine treatment after relapse with higher response rates (38 vs. 18%, P < 0.05) and longer time to progression (23 vs. 19 weeks, P = 0.03) for controls. 94/176 received chemotherapy after relapse again with higher response rates (47 vs. 23%, P = 0.05) and longer time to progression (17 vs. 9 weeks, P = 0.03) for controls. Despite this, survival after relapse was the same for the two groups (median 16 months). However, on subgroup analysis, postmenopausal patients who had received adjuvant CMF had shorter survival (P = 0.03). These results suggest that prior adjuvant therapy should be a stratification factor in clinical trials in advanced disease. PMID- 8217356 TI - Laser surgery for small perianal neoplasms. AB - Excisional laser surgery was used to treat 62 patients suffering from perianal, perineal, and anal canal neoplasms. 48 patients had benign epithelial or pigmented tumours, 12 had carcinoma in situ and 2 had invasive squamous cell carcinoma. Laser surgery was performed under local anaesthesia, in association with the operating microscope on an outpatient basis. 59 out of 62 patients (95%) had clear margins of resection after primary laser surgery, and 3 patients required a second excision for uncleared margins. 3 patients of the group of carcinoma in situ recurred, and 2 had new disease in an untreated area. These patients underwent re-section with the same technique. No significant local complications were observed for single or multiple operations at the perianal and anal canal level. All patients are disease-free in a follow-up ranging from 4 to 113 months, with a median of 25 months. Laser excisional surgery appears to be a suitable method for treating superficial tumours. PMID- 8217357 TI - Importance of the irradiation timing within a chemoradiotherapy sequence including cisplatin and 5-FU-folinic acid. Experimental results. AB - The objective of the present in vitro study was to determine an optimal timing of the irradiation in the combination cisplatin (CDDP) and 5-fluorouracil-folinic acid (5-FU-FA) allowing a maximal cytotoxic effect on a human cell line derived from a head and neck carcinoma (CAL 27 cells). The various tested chemoradiotherapy sequences were applied in parallel to human keratinocytes in culture (SVK 14 cells). This was done in order to define the best sequence allowing the achievement of an optimal selectivity of the cytotoxic effects. The drug sequence was: CDDP over 2 h then fresh medium was added including the tandem 5-FU-d,I FA applied 6 h after CDDP, for 5 days. Irradiation was applied only once and at various times within the drug sequence. The cytotoxicity effects of the different chemoradiotherapy combinations were assessed by the MTT semi-automated test. The part taken by the 5-FU-FA combinations in the overall cytotoxicity was examined; an effect was apparent on CAL 27 cells only. The evolution of the radiation effect (RE = cell survival after drugs/cell survival after drugs plus irradiation) was analysed as a function of the different times of irradiation within the given drug sequence. Clearly, the RE values were dependent upon time at which the radiation dose in the chemoradiotherapy regimen was administered. For CAL 27 cells, irradiation effects were maximal at the first irradiation time tested after the end of the CDDP exposure (i.e. t = 3.5 h). In contrast, this optimal chemoradiotherapy timing for better cytotoxicity on CAL 27 cells did not correspond to that of SVK 14 cells. Consequently, it was possible to establish that the best time for the selectivity index was located shortly after the CDDP exposure. PMID- 8217358 TI - Comparative pharmacological, toxicological and antitumoral evaluation of free and liposome-encapsulated cisplatin in rodents. AB - The systemic toxicity and efficacy of cisplatin (CDDP) were examined in vitro and in vivo. Procedures were performed before and after the antineoplastic agent was encapsulated into multilamellar liposomes (L-CDDP). In vitro cytotoxicity evaluation in L1210 murine leukaemia and NIH OVCAR human ovarian cancer cells showed IC50 values of 0.14 and 0.05 micrograms/ml with CDDP or L-CDDP, respectively. In vivo, mice injected intravenously with L-CDDP had plasma levels of platinum 4-fold higher than with CDDP. The t1/2 alpha was 2 h and the t1/2 beta exceeded 48 h with L-CDDP; whereas a t1/2 alpha of 15 min and t1/2 beta of 12 h was observed with CDDP. The values of platinum in liver, spleen, kidneys, lungs and heart were substantially higher in L-CDDP-treated compared to CDDP treated mice. Cytotoxic evaluation of both agents was tested in vitro (murine L1210 leukaemia and NIH OVCAR cell line) and in vivo (male CD2F1 mice). CDDP and L-CDDP showed similar cytotoxicity in tissue culture. At the highest dose given, 12 mg/kg intraperitoneally (i.p.), L-CDDP showed higher antitumour efficacy demonstrated by an increased life span of the mice. The CDDP treatment at the highest dose was lethal to all the tumour bearing mice. The nephrotoxicity in rats (blood urea nitrogen and creatinine evaluation) of L-CDDP administered i.p. was significantly less than with CDDP. In addition, the ability of kidney slices to transport organic anions [para-aminohippurate (PAH)] and consume O2 was substantially decreased in rats treated with free CDDP compared to L-CDDP. Accordingly, the liposomal encapsulation of CDDP attenuates its nephrotoxicity, but allows maintenance of antitumour efficacy and may be a potentially effective modality in clinical settings. PMID- 8217359 TI - Randomised study of immunotherapy with OK-432 in uterine cervical carcinoma. AB - OK-432, a streptococcal preparation, was administered to patients with stage Ib and II cervical carcinoma except for adeno- and adenosquamous carcinomas. To evaluate the efficacy of OK-432 precisely, 177 patients were stratified by clinical stage, radiotherapy, and lymph node metastasis after complete radical hysterectomy and pelvic lymphadenectomy. Within each stratum, patients were divided randomly into OK-432 and control groups. 85 patients received OK-432 and 92 patients did not. No significant difference was observed in overall 5-year disease free rates between the OK-432 and the control groups, although the mean diameter of erythema on SU-polysaccharide (SU-PS) skin test was larger in the OK 432 group than in the control group. In stage IIb, a significant difference was observed between the OK-432 and control groups. This difference, however, could be attributed in part to the different incidence of the lymph node metastasis. In stage II without lymph node metastasis, 5-year disease free rate was significantly higher in the OK-432 group. PMID- 8217360 TI - The impact of geographical, clinical, dietary and radiation-induced features in epidemiology of thyroid cancer. AB - Cancer of the thyroid accounts for less than 1% of all cancers recognised each year, but the incidence is rising. Much of the early work of the epidemiology and aetiology of thyroid cancer was based on the assumption that thyroid cancer can be treated as an entity. The recognition that two distinct types of endocrine cell occur within the thyroid has made it clear that any discussion of the aetiology and epidemiology of thyroid malignancies must take into account the histological classification of these tumours. Moreover, there are difficult problems to be considered when comparing thyroid cancer incidence across tumour registries, because of a lack of standardisation or morbidity data collection, difficulties in histological diagnosis, varying rates of diagnosis of occult papillary carcinoma, and prevalence and techniques of autopsies. So far only a relatively small proportion of thyroid cancer cases can be explained with adequate certainty as regards epidemiology and aetiology. As in cancer in general, the aetiology and epidemiology of thyroid cancer in detail remains unknown in the majority of cases. PMID- 8217361 TI - Colon cancer in seven siblings. AB - In a case-control study of cancer of the colon it was found that 96 out of 332 (29%) cases had a positive family history of cancer of the colon (2 cases and more) as compared with 19 out of 473 (4%) controls. 3 colon cancer cases reported that 6 of their respective relatives were also affected with the same cancer. We were able to do a complete follow-up study of one family where 7 out of 12 sibling (P < 0.05) had confirmed pathological diagnoses of cancer of the colon. The mean age at diagnosis among these familial colon cancer cases was 64 years (60 years for females and 73 years for males) and all tumours were located in the caecum or right colon (a common characteristic of colon cancer in this family). There was no history of familial adenomatous polyposis in this family. It is unlikely that the significantly high proportion of familial colon cancer found could be due to chance. This suggests that both environmental and genetic factors play an important role in the aetiology of colon cancer. PMID- 8217362 TI - Breast cancer in the southeastern Netherlands, 1960-1989: trends in incidence and mortality. AB - Temporal trends in incidence and mortality in breast cancer were examined in the southeastern Netherlands using data from the population-based Eindhoven Cancer Registry. In the period 1960-1989 the incidence rate of first primary breast cancer approximately doubled in all age groups. The increase mainly occurred before 1975 and after 1985, when no screening activities were performed. This trend appeared to be a result of an average yearly increase in incidence of localised and distant tumours with both 4.6%, whereas the incidence of regional tumours did not change. Simultaneously, breast cancer mortality remained unchanged in women aged under 60, and only increased by a yearly average of 0.7% in women aged 60-74 and of 0.9% in women aged 75 and over. These differing trends in incidence and mortality, which can only partially be explained by earlier detection, suggest an improved survival of breast cancer. PMID- 8217363 TI - 3'-Deamino-3'-(2-methoxy-4-morpholinyl)-doxorubicin (FCE 23762): a new anthracycline derivative with enhanced cytotoxicity and reduced cardiotoxicity. AB - The purpose of this study was to examine the cytotoxicity and cardiotoxicity of the new doxorubicin derivative, 3'-deamino-3'-(2-methoxy-4-morpholinyl) doxorubicin (FEC 23762). The concentration of FCE 23762 that resulted in a 50% reduction in colony formation of DU 145, COLO 320DM, A549 and A2780 human cancer cell lines ranged from 1.1 and 3.2 nmol/l and was 3-9 times as low as doxorubicin. In the isolated perfused rat hearts, doxorubicin 10(-5) mol/l induced a significant prolongation of S alpha T segment and Q-Fmax interval, and reduction in dF/dtmax and coronary flow while only FCE 23762 10(-5) mol/l induced a widening of QRS complex. Anaesthetised rats given a single intravenous (i.v.) dose of doxorubicin 10 mg/kg showed significant changes in both ECG (S alpha T segment and QRS complex enlargement) and haemodynamic parameters (increase in mean arterial blood pressure and reduction in systemic arterial dP/dtmax), while animals given FCE 23762 (0.1 and 0.3 mg/kg) had a significant increase in QRS complex duration after the highest dose. In the chronic cardiotoxicity study animals receiving FCE 23762 (0.03 mg/kg i.v. once a week for 3 weeks) did not show any significant alteration of ECG and minor changes of cardiac histological picture; by contrast doxorubicin (3 mg/kg i.v. once a week for 3 weeks) induced a severe cardiomyopathy, characterised by progressive widening of S alpha T segment, increase in T wave and histological damage consisting of vacuolations and loss of myofibrils. These results indicate that FCE 23762 is more active in vitro than doxorubicin and markedly less cardiotoxic in vivo at the doses used in the present study. PMID- 8217364 TI - Cytotoxic effects of anticancer agents on subconfluent and multilayered postconfluent cultures. AB - The cytotoxic effects of conventional (doxorubicin, 5-fluorouracil, cisplatin) and investigational (2',2'-difluorodeoxycytidine, hexadecylphosphocholine, EO9, rhizoxin) anticancer drugs were studied in subconfluent and multilayered postconfluent cultures of human colon and ovarian carcinoma cell lines. Chemosensitivity was assessed 4 days after a 24-h drug exposure with the sulphorhodamine B assay. Except for rhizoxin, all drugs tested yielded an EC50 (drug concentration producing absorbance readings 50% lower than those of non treated wells) in postconfluent cultures that were higher than an EC50 obtained with subconfluent cultures. Compared with subconfluent cultures, postconfluent cultures showed decreased cellular nucleotide concentrations and ATP/ADP ratios, in addition to an increased percentage of G0/G1 cells. The activity of DT diaphorase, a reductase involved in the bioactivation of EO9, was similar in sub- and postconfluent cultures. These results indicate similarity of the postconfluent model presented with those obtained with in vivo models and more complex in vitro techniques. PMID- 8217365 TI - Genistein inhibits tumour cell growth in vitro but enhances mitochondrial reduction of tetrazolium salts: a further pitfall in the use of the MTT assay for evaluating cell growth and survival. AB - The natural isoflavone genistein inhibits the growth of a number of tumour cell lines in vitro. During investigations on the antiproliferative effects of genistein we observed that, with respect to direct cell counting, a tetrazolium (MTT) colorimetric assay consistently underestimated the growth inhibitory activity of the substance. Cell proliferation was markedly inhibited by genistein in three tumour cell lines (MCF-7, human breast tumour; Jurkat cells, human T cell leukaemia; L-929, mouse transformed fibroblasts) when cell number was evaluated by direct counting, whereas a 72-h MTT assay failed to reveal any growth-inhibitory effect. Cell cycle analysis by propidium iodide staining and flow-cytometry revealed a G2/M cell cycle arrest after genistein treatment. Genistein-treated cells displayed an increase in cell volume and in mitochondrial number and/or activity, as revealed by enhanced formazan generation and increased uptake of the vital mitochondrial dye rhodamine 123. These results suggest that alterations in cell cycle phase redistribution of tumour cells by genistein may significantly influence mitochondrial number and/or function and, consequently, MTT reduction to formazan. This may constitute an important bias in analysing the effects of genistein, and possibly other drugs that block the G2/M transition, on growth and viability of cancer cells in vitro by MTT assay. PMID- 8217366 TI - Disease-related differences in antibody patterns against EBV-encoded nuclear antigens EBNA 1, EBNA 2 and EBNA 6. AB - Antibodies to Epstein-Barr virus (EBV) nuclear antigen family (EBNA) and three of its individual members, EBNA 1, EBNA 2 (A and B) and EBNA 6, were measured by anticomplement immunofluorescence (ACIF) in sera of 75 healthy controls, 13 patients with chronic EBV infection, 38 with non-Hodgkin lymphoma (NHL), 23 with Hodgkin's disease (HD), 105 with nasopharyngeal carcinoma (NPC) and 7 patients with infectious mononucleosis (IM). Their anti-EBV lytic antigens were also measured. We observed that: (1) anti-EBNA 2A and E6 rose in parallel 4-6 weeks after IM, followed by anti-EBNA 1 at 3-6 months, (2) all seropositive individuals had anti-EBNA 1; 74% also had anti-EBNA 2A and E6, (3) anti-EBNA 1 accounted for most of the anti-EBNA reactivity in non-IM sera. Striking disease-associated differences were noted on the humoral responses to the lytic and transformation associated antigens. Compared to the controls, anti-EBNA 1, -EBNA 2A and -EBNA 6 were simultaneously four to 10 times higher in chronic reactivations, whereas only anti-EBNA 1 was elevated (10 times) in NPC. Individual EBNA titres were normal in NHL or HD patients. PMID- 8217367 TI - Phase II study of cystemustine in metastatic colorectal carcinoma. A trial of the EORTC Clinical Screening Group. AB - 27 patients with metastatic colorectal carcinoma were treated, every 2 weeks, with 60 mg/m2 cystemustine, a new chloro-2-ethyl nitrosourea derivative. Haematological toxicity was the major side-effect including neutropenia and thrombocytopenia. We did not observe any complete or partial response. Cystemustine, with this dose and this schedule, has no activity in colorectal cancer. PMID- 8217368 TI - Hypercalcaemia in small cell lung cancer: report of a case associated with parathyroid hormone-related protein (PTHrP). AB - Although hypercalcaemia is frequently associated with malignancy, it is very rare in small cell lung cancer despite the high incidence of lytic bone metastases. We report a patient with extensive small cell cancer who presented with hypercalcaemia. Investigations suggested parathyroid hormone (PTH) receptor stimulation, although the serum PTH level was not elevated. PTH related protein (PTHrP) was localised in a biopsy specimen from the tumour. Although hypercalcaemia is rare in small cell lung cancer, when hypercalcaemia does occur, PTHrP may be a causal factor. PMID- 8217369 TI - The use of immunotoxins for cancer therapy. PMID- 8217370 TI - Cancer incidence in the Commonwealth of Independent States, the Baltic States and Georgia--the former U.S.S.R. PMID- 8217371 TI - High-dose consolidation chemotherapy in infants with stage 4 neuroblastoma. The European Group for Bone Marrow Transplantation. PMID- 8217372 TI - Carboquone combined with methotrexate and 5-fluorouracil for recurrent and advanced ovarian cancer. PMID- 8217373 TI - Phase II study of cisplatin, 5-fluorouracil and folinic acid in patients with carcinoma of unknown primary origin. PMID- 8217374 TI - Chemosensitisation effect of verapamil and cyclosporin A in vitro is reduced under acidic pH conditions. PMID- 8217375 TI - Undergraduate education about cancer. A survey of clinical oncologists and clinicians responsible for cancer teaching in Australian medical schools. AB - Undergraduate cancer education in Australian medical schools is not integrated and there is little evidence of change in content or structure in recent years in spite of major changes in knowledge about cancer epidemiology and cancer biology, and in cancer management. A recent survey of graduating students/interns from all Australian medical schools revealed a disturbing variability in experience and lack of important knowledge. There was evidence of substantial differences in knowledge of, and rating of teaching between the different disciplines involved in cancer control and cancer management. To examine possible reasons for this, we surveyed cancer clinicians and teachers of oncology in the undergraduate curriculum at Australian medical schools. We asked them the same questions of knowledge as the students, and also to comment on the type and emphasis of teaching desirable in the medical students' cancer curriculum. The results indicate not only that the survey instrument was seen to be relevant, but also that some of the bias and misinformation detected in the student experiences may be attributed to attitude, knowledge and differences of opinion of the teachers. The results highlight the need for an integrated cancer curriculum to inform graduates about an illness which will be diagnosed in more than a quarter of the Australian population. PMID- 8217376 TI - Reducing the risk of cancers. A distance learning resource for cancer prevention throughout the EC. AB - This paper describes an initiative in distance learning for cancer prevention for health care professionals throughout the EC. 'Reducing the Risk of Cancers' is a multi-media integrated study pack of learning materials prepared by the Open University (U.K.) with funding from the Europe Against Cancer programme of the European Commission. The teaching materials aim to enhance cancer prevention and health promotion skills and competencies amongst health care professionals at local level. In the paper the background to the pack is considered, the production process is described and the aims and philosophy of the teaching materials are outlined. The content of the pack is described and usage, dissemination and evaluation for health professionals throughout Europe are discussed. PMID- 8217377 TI - The educational programmes of the European Community. PMID- 8217378 TI - [Langerhans cells do not influence the postoperative survival of esophageal epidermoid carcinoma]. AB - OBJECTIVE: Langerhans' cells (LC) in several tumors have been related to a better postoperative prognosis. We have performed the present study in order to verify this hypothesis for oesophageal squamous cell carcinoma (OSCC). EXPERIMENTAL DESIGN: A retrospective analysis of histologic preparations of OSCC was made. For the identification of LC, the deparaffinized sections were stained with anti S 100 protein antibody using the avidin-biotin-peroxidase complex (ABC) method. We assessed the presence of LC in the whole tumour, in the stroma and in the epithelium. We also analyzed their influence on postoperative survival and their relation to histologic differentiation, wall involvement, peritumoral lymphocytic infiltration and microscopic growth type. PATIENTS: 35 patients who underwent standard esophagectomy for OSCC. None had received radiotherapy and none died from postoperative complications. RESULTS: LC were found in 88.6% of patients. In 31.4% only in the epithelium and 17.1% exclusively in the stroma. Mean cellular density was greater in epithelium (NS). A higher two-year survival was found in patients with a greater cellular density without statistical significance. More than 15 LC/mm2 were associated with infiltrative growth type tumors whereas less than 15 LC/mm2 were associated with infiltrative growth type ones (P < 0.01). No statistical significant correlations were found with other parameters. CONCLUSIONS: Our results do not support an influence of the LC on the OSCC postoperative survival. We have shown an association between LC density and growth type but its significance is still undetermined. PMID- 8217379 TI - [Intraluminal anorectal ultrasonography in the staging of anal canal cancer]. AB - The staging of anal canal carcinoma is essential to establish the surgical procedure, either a local excision or abdominoperineal resection. In addition to the conventional studies we have used the anorectal endosonography in seven patients with carcinoma of the anal canal. The preoperative staging was done according to the UICC classification. The endosonography gave significant information of the anal anatomy to assess an accurate diagnosis in six patients, two of them had tumors invading the vagina. In one case, the ultrasound image was underestimated. Overall accuracy of the endosonographic assessment was 85.7 percent. Anorectal endosonography correctly assesses the anatomy layers of the anal canal and offers a good tumor's staging. PMID- 8217380 TI - [Chemoprophylaxis of secondary peritoneal hydatidosis. Experimental study]. AB - We have studied the effectiveness of pharmacologic prophylaxis of experimental peritoneal hydatidosis. Mice (n = 140, divided in ten groups) suffered intraperitoneal contamination with protoscoleces of E. granulosus from sheep. Each group received different treatment (mebendazole, praziquantel, or both), in three different schedules (during 3 days before contamination, during 7 days after contamination, or both before and after Mebendazole 150 mg/kg-day), praziquantel (25 mg/kg-day) were given in three daily doses. Mice were sacrificed six months later and the number and type of existing peritoneal cysts was recorded. Prophylaxis prior to contamination was shown ineffective. Early treatment greatly decreased the severity of the peritoneal hydatidosis. The administration of the drug before and after contamination, did not improve the results obtained when the drug was given after contamination. Both mebendazole and praziquantel were effective, though the former obtained better results. The association of both drugs does not improve the results obtained with mebendazole alone. These experimental results recommend the early use of mebendazol or praziquantel after open surgery for hydatidosis, in order to prevent the occurrence of secondary peritoneal hydatidosis. PMID- 8217381 TI - [Hepatitis B markers at 3 open centers for mentally retarded]. AB - With the aim of investigating the prevalence of hepatitis B virus infection, we studied 161 mentally retarded patients with an age range of 1 to 56, in three open institutions from the Safor Area (Valencia). Some positive serum markers of HBV infection were found in 15 patients (9.3%). The mentally retarded older than 17, presented a prevalence of HBV markers (20.6%), in contrast to those under this age (1.1%) and against the control group (5.1%) (p < 0.001). HBsAg positive markers were found in three cases, representing 4.4% among the older than 17's, against 0.4% of the general population (p < 0.05). There was some positive correlation with personal history of hepatitis (p < 0.01) and severely handicapped patients (p < 0.05) an there was no association with sex, duration of stay and Down's Syndrome. Our results indicate that seropositive B prevalence is similar to the general population in the mentally retarded younger than 17 years old and higher from this age on, which confirms the need for active prophylaxis in the youngest of this collective. Reviewing the Spanish studies we observe a lower prevalence of HBsAg(carriers) and HBV markers in open institutions than in closed institutions. PMID- 8217382 TI - [Infected pancreatic necrosis. Reexaminations planned with locoregional anesthesia]. AB - Eleven patients with infected pancreatic necrosis are presented. They were treated with necrosectomy and lavage with programmed reexploration and peridural anesthesia. Nine of these patients, had biliary stone disease as associated pathology and two were chronic alcoholics. We used the contrast computerized tomography and CT-guided percutaneous aspiration to obtain fluid for Gram stains and culture, as a diagnostic method. The patients were reoperated 3 to 5 times each 48-72 hs., with a mortality of 18.2%. PMID- 8217383 TI - [Diagnostic value of aspiration cytology with ERCP]. AB - ERCP is of great value in diagnosing malignant pathology of the biliopancreatic duct system. However, the ERCP endoscopic characteristics in malignant stenosis often lack specificity and are difficult to differentiate from those of chronic pancreatitis. In these cases histological confirmation is essential to diagnosis. With the aim of increasing the diagnostic possibilities of ERCP in pancreatic cancer--particularly when associated with chronic pancreatitis--we performed aspiration cytology of pancreatic juice obtained via endoscopic cannulation of the main pancreatic duct using ERCP in 102 patients with suspected periampullar pathology, chronic pancreatitis and/or pancreatic cancer. The diagnostic sensitivity of cytology for pancreatic malignancy was 33.3%, versus 60% for cancer of Vater's papilla. Specificity was 100% in both cancers. We observed no false positive results or complications. On combining both techniques, i.e., ERCP and cytology of the pancreatic juice, sensitivity increased to 100% for pancreatic malignancy, 77.7% for chronic pancreatitis (characteristic ERCP radiographic images and absence of neoplastic cells) and 100% in the case of ampullomas. Difficulties in the differential diagnosis between advanced chronic pancreatitis and pancreatic cancer persist with ERCP alone. In such cases aspiration cytology may secure a definitive diagnosis--particularly when neoplastic cells are demonstrated (Class IV). PMID- 8217384 TI - [Digestive hormones]. PMID- 8217385 TI - [Gastric duplication in an adult]. AB - A gastric cystic duplication was found in a 83 year old patient; the cyst was located on the posterior wall of the stomach and required a total gastrectomy. Gastric duplications are usually discovered during the first year of life. They are located in the greater curvature. It's common the cystic form without communication with the gastric lumen. Due to its rarity, in most cases the diagnosis is made at laparotomy. PMID- 8217386 TI - [Surgical indications in acute pseudo-obstruction of the colon (Ogilvie syndrome)]. AB - Acute pseudo-obstruction of the colon (APC), popularly known as Ogilvie's syndrome, has been the subject of numerous medical communications in the past two decades. In this paper three patients with APC managed surgically are presented. In two patients cecal perforation developed; in the third patient a discharge cecostomy was carried out because of a caecal diameter of 16 cm. Indications for the operative management of these patients include pneumoperitoneum, development of peritonitis in the area of the cecum, continued cecal distention after 48-72 hours of therapy with or without colonoscopy, cecal diameter greater than 12 cm, respiratory failure and uncertain diagnosis. PMID- 8217387 TI - [Cecovesical fistula of inflammatory origin simulating neoplasm of the cecum]. AB - We describe a case of a caecovesical fistula in a 60-year-old woman caused by an inflammatory tumour of a probably appendicular origin which mimicked cancer of the caecum. The patient, had a history of idiopathic peripheral polineuropathy and chronic constipation. Presented urinary tract infection and fecaluria, without symptoms of appendicitis. At operation, a solid mass including the caecum and the fundus of the bladder was found, and the appendix was not identified. In view of the neoplastic appearance and the impossibility of separating the caecum from the bladder, "en bloc" right hemicolectomy and partial cystectomy were performed. The pathologic study showed the inflammatory nature of the lesion. PMID- 8217388 TI - [Cancer of the middle third of the choledochus: an infrequent diagnosis]. AB - We report the case of an 80-year-old woman with a previous history of HBP, hysterectomy due to cancer of the uterus and cholelithiasis, who was admitted in our hospital because of diffuse abdominal pain, marked jaundice, choluria and acholia during one week, together with anorexia and loss of weight. Blood chemistry results disclosed a total bilirubin of 11 mg/dl, a direct bilirubin of 8 mg/dl, GGTP 826 U/I, alkaline phosphatase 287 U/I, AST 285 U/I, ALT 837 U/I and LDH 242 U/I. The CA 19-9 marker was higher than 500 U/ml. The abdominal ultrasound examination did not show any space-occupying lesions; the extra and intrahepatic bile ducts were very dilated and the gall bladder showed multiple stones within its contents. The endoscopic retrograde cholangiopancreatography (ERCP) showed a homogeneous filiform defect at the middle third of the common bile duct of approximately 1 cm in length and with a marked dilatation of the bile ducts. A percutaneous drainage of the bile tree was performed, but the patient died. PMID- 8217389 TI - [Retroperitoneal hibernoma]. AB - We report a new case of retroperitoneal hibernoma. Hibernoma is a rare, benign soft tissue tumor whose constituent cells resemble those of brown fat tissue, which is present in human fetus and newborn infant and it gradually diminishes in quantity throughout adult life. Retroperitoneal location is unusual. Differential diagnosis with the liposarcoma (the most frequent tumour on this location) is based on the high vascularity of the hibernoma. Total resection of the tumour can achieve complete cure without recurrence nor metastasis. PMID- 8217390 TI - [Severe lower digestive hemorrhage caused by Meckel's diverticulum]. PMID- 8217391 TI - [Giant abdominal lipoma]. PMID- 8217392 TI - [Nerves of the liver]. PMID- 8217393 TI - [Posterior fossa dural arteriovenous fistula with isolated sinus segment]. AB - Radiological and clinical analysis was performed in 5 patients with posterior fossa dural arteriovenous fistulas (DAVFs) with isolated sinus segment due to sinus thrombosis, and their patho physiological, diagnostic, and therapeutic concerns were discussed. Patients ranged in age from 36 to 73 years old with a mean of 57 years and included 2 males and 3 females. Two patients presented with ataxia, one with ataxia and bruit, one with atypical facial pain, and one with parietal dysfunction. One patient had a history of hemorrhagic event. DAVFs were located at transverse-sigmoid sinus (3 cases), superior petrosal sinus (1 case), and straight sinus (1 case). They were fed by many branches of external carotid artery including middle meningeal artery, ascending pharyngeal artery, posterior auricular artery, occipital artery, meningeal branches of vertebral artery and posterior cerebral artery, and meningohypophyseal trunk of internal carotid artery. Shunt flow drained into contralateral transverse-sigmoid or supratentorial sinuses via the isolated venous segment through markedly dilated cortical and/or deep venous systems, which caused altered normal venous drainage pattern and venous hypertension. Transarterial embolization in multiple stages (mean 3.4) using n-butyl cyanoacrylate (NBCA) could alleviate symptoms in all cases. DAVFs were almost totally obliterated in 3 patients. Further embolization in one case, and surgical excision in one case were planed because of some residual dilated cortical venous drainage. Posterior fossa DAVFs with isolated sinus segment accompany markedly dilated cortical and/or deep venous systems. They could cause cerebellar, brainstem, or cranial nerve dysfunctions, and sometimes present distant supratentorial symptoms or hydrocephalus due to abnormal venous drainage and venous hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217394 TI - [Prediction of outcome in putaminal hemorrhage]. AB - We obtained information on patients with putaminal hemorrhage (3,638 medically treated cases and 3,372 surgically treated cases). With these data, we have developed easily applicable and clinically useful prediction models for both mortality and activities of daily living (ADL) at three months after admission. We derived these models by Hayashi's discriminant technique for categorical data. Before their derivation, variables generally available on the initial day of hospitalization and possibly related to outcome were examined individually with tests of homogeneity. Neurological grading (NG), age, deformity of cisterns around midbrain, midline shift, hematoma volume, and motor paralysis were identified as candidate predictors of both mortality and ADL. CT classification was also added to the predictors of ADL. Initially, all these factors were included in tentative models, and then those which were found not to contribute substantially to the prediction were deleted. Ultimately, we proposed two models, one for mortality and the other for ADL. The mortality model used NG, hematoma volume, and deformity of cisterns around midbrain as predictors, and the ADL model used age, NG, CT classification, hematoma volume, and motor paralysis. Average correct classification rates were 87% (medical) and 69% (surgical) for mortality, and 64% (medical) and 60% (surgical) for ADL. With these models, we evaluated indications of both kinds of treatment by comparing each predicted ADL of the medically treated cases with that of the surgically treated cases. PMID- 8217395 TI - [Bone changes in Parkinson's disease]. AB - Parkinson's disease (PD) is a movement disorder and tends to occur in elderly people, who sometimes develop age-related osteoporosis. Pathological bone changes seem to affect the outcome and prognosis of PD. We studied the relationship between bone changes and PD. Bone examination was conducted by multiple scanning X-ray photodensitometry in 70 patients with PD and 46 age-matched controls. We then compared the results with the clinical characteristics of PD. Of the 70 patients, 44 were women and 26 were men; the mean ages were 65.5 +/- 7.9 (mean +/ SD) and 63.4 +/- 9.9 years, respectively. Of the 46 controls, 25 were women and 21 were men, with mean ages of 61.4 +/- 10.2 and 60.3 +/- 9.3 years, respectively. Osteopenia was detected in 26 (59%) of the 44 female, and 5 (19%) of the 26 male patients, and in 6 (24%) of the 25 female and 2 (9%) of the 21 male controls. The frequency of osteopenia was significantly greater in the female patients than in the male patients or the female controls. The mean Hoehn & Yahr stage of female patients with osteopenia was more severe than that of those without osteopenia, with a significant difference between the two groups. Osteopenia in men was related to the duration of PD, but this was not so in the women. The female patients without osteopenia tended to have earlier onset of PD and longer duration of the disease and treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217396 TI - [A case of isolated adrenocorticotropic hormone deficiency with adrenocorticosteroid-responsive brain edema and repeated confusions]. AB - A 60-year-old man developed confusional state with severely abnormal electroencephalogram and brain edema on computed tomography (CT) of brain. Adrenocorticosteroid therapy was dramatically effective for the confusional state and brain edema. The reduction of adrenocorticosteroid induced confusional states, and they disappeared with the increase of adrenocorticosteroid. When brain edema on CT disappeared, T 2-weighted magnetic resonance imagings revealed diffuse high signal in the white matter. A diagnosis of isolated adrenocorticotropic hormone deficiency was made by endocrinological examinations and clinical features. We suggest that brain edema in this patient is due to deficiency of glucocorticoid. High intensity area in the white matter may show the degeneration of the white matter following brain edema. PMID- 8217397 TI - [An autopsied case of type 2 Machado-Joseph's disease or spino-pontine degeneration]. AB - The authors present the clinico-pathological findings in a member of a family residing in Akita Prefecture located in the north-eastern region of Japan. Four members in three generations of the family developed ataxia. The autopsied patient was a 42-year-old woman, who, at the age of 25, had developed progressive cerebellar ataxia with pyramidal spasticity and increased deep tendon reflexes predominant in the lower extremities. However, she retained fine movement of the hands and fingers and showed no dysarthria until the age of 35. She could no longer walk unassisted at 38 years old. She showed cerebellar ataxia in both hands and legs, dysarthria, bulging eyes, progressive extraoculomotor palsy with nystagmus, bradykinesia, sensory disturbance, and dystonia in the face, upper extremities, and fingers. Deep tendon reflexes were decreased, especially in the lower extremities. Subacute generalized muscular atrophy developed at the age of 39. She became bedridden and died of pneumonia. The clinical diagnosis was Type-2 of the entity known in Japan as Machado-Joseph disease. At neuropathological examination, the brain weight was 1,250 g. The spinocerebellar system including Clarke's column and the spinocerebellar tracts were degenerated, but the cerebellar cortex and inferior olivary nucleus were spared. Slight-to-moderate degeneration was observed in the pontocerebellar system. In the dentate nucleus, most of the neurons showed what is known in Japan as "grumose degeneration", but there was no neuronal loss or gliosis. The hilus of the dentate nucleus and the superior cerebellar peduncle were intact.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217398 TI - [A case of chronic progressive external ophthalmoplegia with pituitary hypothyroidism]. AB - We report a case of chronic progressive external ophthalmoplegia with pituitary hypothyroidism. This patient had complained of hearing-loss at the age of fourteen and loss of body weight at fifteen. She was examined by otorhinolaryngologists at large hospitals yearly over a period of 5-6 years, but hearing-loss remained unknown. As her ophthalmoplegia progressed (as is evident from family photographs from the age of sixteen onward), with hindsight it should have been recognized. When examined on October 11, 1991, she complained of ptosis, speech disturbance and dysphagia at the age of thirty-four. Neurological examination revealed limitation of ocular movement, bilateral ophthalmoplegia, facial muscle atrophy, and weak gag reflex. She showed muscle atrophy in her neck including both sternocleidomastoid, major and minor rhomboid, girdle and distal parts of upper and lower extremities. Muscle biopsy of her biceps demonstrated ragged-red fibers, cytochrome c oxidase (CCO) deficient fibers and deletion of mitochondrial DNA. A plain CT scan revealed bilateral periventricular lucency, and a brain MR image showed a normal sized pituitary gland but diffuse high signal intensities in the both periventricular white matter with proton density weighted and T2-weighted axial MR image. And also her electroencephalogram showed diffuse 7 Hz slow waves in all areas and increased slow waves by hyperventilation, and all waves from I to V of the auditory brain stem response disappeared. The effect of TRH on serum TSH secretion was not evident in this patient. This case was ascertained to be chronic progressive external ophthalmoplegia with pituitary hypothyroid function. PMID- 8217399 TI - [Dermoid cyst in the fourth ventricle associated with Klippel-Feil syndrome]. AB - Dermoid cysts in the central nervous system are often associated with various congenital disorders, especially dermal sinus and spina bifida. We report a case of dermoid cyst in the fourth ventricle associated with Klippel-Feil syndrome. A 47-year-old man with a long history of headache had been known to have a cystic lesion in the posterior fossa for 12 years. When he was referred to our hospital with complaints of transient tetraparesis, he showed bilateral cerebellar ataxia and minimal left hemiparesis. Furthermore, he was noted to have a webbed neck with a low hairline and facial asymmetry. CT and MRI showed multiple cerebral infarctions as well as a mass lesion in the posterior fossa. Cervical roentgenogram showed a fusion of C 2 and C 3 vertebrae. The tumor was totally removed via a suboccipital approach, and the diagnosis was a dermoid cyst. The present patient had not only dermoid cyst and Klippel-Feil syndrome but also hypertrophy of the zygomatic bone. The pathogenesis of the Klippel-Feil syndrome is presumed to be an intrauterine defect, with a failure of segmentation of mesodermal somites. The zygomatic bone is also derived from the mesoderm somites at early fourth week, too. From these points of view, the disturbance in the mesoderm before the fourth week of gestation might have played an important role in causing a dermoid cyst. PMID- 8217400 TI - [Giant plasmacytoma of the skull which appeared in the clinical course of multiple myeloma--a case report]. AB - A 51-year-old woman with large plasmacytoma occurring from the temporal bone is presented. She has a history of multiple myeloma for 9 years. She manifested marked swelling in the left temporal area with tenderness. Neurological examination revealed no abnormality. She showed monoclonal free light chain (lambda type) in the serum and urine, and had multiple osteolytic lesions in her general bones. T1 WI of MRI exhibited a huge mass showing slightly high intensity in the left middle fossa and infratemporal fossa, and a part of the mass protruded into the extracranial space. The mass was markedly enhanced by Gd-DTPA. Angiography showed a hypervascular mass supplied by the external carotid artery. Biopsy disclosed plasmacytoma. She underwent local irradiation of 30 Gy and chemotherapy of Ranimustine (100 mg) and Cyclophosphamide (400 mg). The tumor reduced its size, and tenderness in her temporal area disappeared. PMID- 8217401 TI - [Circadian rhythm disturbance after radiotherapy for brain tumor in infantile period--clinical effect of L-thyroxine and vitamin B12]. AB - We reported here 19-year-old man suffering from circadian sleep-wake (S-W) rhythm disturbance after total tumor resection and whole brain irradiation. This 19-year old man was diagnosed as having astrocytoma in the right temporal lobe by CT scan and angiography at the age of 6 months. After total tumor resection and whole brain irradiation (60Co 60 Gy), he showed profound psychomotor retardation, endocrinologic dysfunction including hypothyroidism and growth hormone deficiency, and sleep-wake rhythm disturbance. At the age of 19, brain MRI revealed asymmetrical low intensity in the hypothalamic region. On endocrinological examination panhypopituitarism due to primary hypothalamic lesion was evident. His S-W rhythm was disturbed showing a dispersed type sleep, i.e., sleep periods were dispersedly distributed throughout the 24 hours. So he showed a lethargic tendency in the daytime. All-day polysomnography revealed abnormal sleep structure such as the absence of sleep spindle and hump, peripheral apnea, snoring and low oxygen saturation. After L-thyroxine supplementation his daily activity improved gradually. The decrease in short time sleep and tendency of a free-running rhythm were observed and oxygen saturation improved remarkably. Peripheral apnea and snoring disappeared. The wakening effect of L-thyroxine administration may be due to improvement of hypothyroidism symptom such as myxoedematous pharynx. In addition, it seems related to the alteration of the central S-W rhythm regulation, because free-running rhythm appeared after L-thyroxine administration. Vitamin B12 (VB12), which has been reported to be effective for sleep-wake rhythm disorders, was not effective for our patient's free-running rhythm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217402 TI - [Asynchronous Bell's phenomenon in progressive supranuclear palsy]. AB - A 60-year-old man suffering from progressive supranuclear palsy showed asynchronous Bell's phenomenon and apraxia of eye-lid opening. He showed synchronous upward rotation of the eyeball at closing eyes. Although apraxia of eye-lid opening was observed in both sides, eye opening of the right side took longer duration than that of the opposite side. When he tried to open his eyes, unilateral Bell's phenomenon was sustained in the side of involuntary eye closing for a several seconds. These findings indicated disorders of the coordination of eye opening-and-closing, which regulate the orbicural muscle of eye, levator muscle of upper eyelid and external ocular muscles. And the mechanism of synchronous eye movement between the both sides was also disturbed. The administration of L-droxydopa was effective to gait disturbance, but not to ocular movement disorder including impaired Bell's phenomenon. The pharmacological results suggested different neuron system between locomotion control and conjugation affected in this disease. PMID- 8217403 TI - [MRI and SPECT of adrenoleukodystrophy (cerebello-brainstem dominant form)--a case report]. AB - We reported a 28-year-old man with adrenoleukodystrophy showing neurological features of olivopontocerebellar atrophy. He had a 11-year history of Addison's disease. ACTH stimulation produced no rise in the plasma cortisol level. The ratios of C24:0/C22:0, C25:0/C22:0, and C26:0/C22:0 in fatty acids of sphingomyelin from plasma were all increased. MRI showed the atrophy of brainstem and cerebellum and the abnormal hyperintense lesions of the bilateral pyramidal tracts in the brainstem and internal capsule. 99mTc-HM PAO SPECT showed hypoperfusion of the deep white matter, frontal lobes, temporal lobes, and cerebellum. We suggest that SPECT may be useful for detection of subclinical lesions in ALD. PMID- 8217404 TI - [Peripheral neuropathy in large granular lymphocytic leukemia]. AB - A 16-year old woman with LGL leukemia developed peripheral neuropathy. She showed virus-associated hemophagocytic syndrome (VAHS)-like signs including high fever, liver dysfunction, huge splenomegaly, hepatomegaly and pancytopenia. The presence of chronic active EB virus infection was proved by marked high titers for IgG and IgA antibodies to the Epstein-Barr viral capsid and early antigens and low titers of antibody to Epstein-Barr nuclear antigens. She showed dysesthesia and paresthesia of bilateral lower extremities with marked swelling and tenderness, and later developed muscular weakness and atrophy with areflexia of lower extremities. Findings of the central nervous system dysfunction were not observed except for the acceleration of jaw jerk. Pleocytosis and increased protein levels in the cerebrospinal fluid were found. Pulse therapy of methyl-prednisolone and high dose intravenous immunoglobulin therapy (20 g/day for 3 days) were effective for neurological findings. The increased neopterin in the cerebrospinal fluid suggested that peripheral neuropathy was caused by activated macrophages. PMID- 8217405 TI - [A 62-year-old man with multiple cranial nerve palsies on the right side and a pelvic mass]. AB - We report a 62-year-old man with a pelvic mass, who developed multiple cranial nerve palsies on the right side. He was well until the summer of 1977 when he developed a numb sensation in the sacral region. In the next year, a huge tumor was found in the sacral area in another hospital. Most of the tumor was resected at that time. Post-operative course was uneventful. In July 1988, there was an onset of weakness in his legs, gait disturbance, and dysuria. Myelography at the above hospital revealed a complete block at the seventh thoracic level. He was treated by laminectomy and post-operative radiation. In June 1990, he developed a neuralgic pan in his right leg. Two months later, he noted diplopia, deafness in his right ear, and swallowing difficulty. He was admitted to our hospital for further work up on January 14th of 1991. On admission, he was afebrile. General physical examination revealed a 4 cm had mass in his right anterior chest attaching the rib. Gynecomastia was noted bilaterally. Liver was felt by 5 cms under the right hypochondrium. The edge of the liver was firm. On neurologic examination he was an alert and mentally sound man. His higher cerebral functions were intact. In the cranial nerves, complete palsy of the abducens nerve, mild nerve deafness, paresis of the soft palate, atrophy and weakness of the sternocleidomastoid and upper trapezium muscles, all on the right side, deviation of the tongue to the right, slurred speech, and dysphagia were observed. The neck was supple. He was able to walk with a support. Mild weakness was present in his right lower extremity. Both legs were spastic. No ataxia or involuntary movements were noted. Deep reflexes were symmetric and normally active. No sensory loss was observed. No meningeal signs were present. Pertinent laboratory findings included moderate anemia (Hb 8.8 g/dl), LDH 2,631 U/l, CRP 7.4 mg/dl. The CSF was under an increased pressure (OP 260 mmH2O) containing 2 lymphocytes/ml, 43 mg/dl of protein, and 49 mg/dl of glucose. Radiologic examinations revealed a destructive change in the sacrum, lytic lesions in the seventh thoracic spine and in the clivus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8217406 TI - [Pathogenesis of cerebral vasospasm following subarachnoid hemorrhage]. PMID- 8217407 TI - [Prevention of cerebral vasospasm with tissue plasminogen activator]. PMID- 8217408 TI - [Treatment of cerebral vasospasm by a protein kinase inhibitor AT 877]. PMID- 8217409 TI - [Cerebral vasospasm and free radicals: a disorder of mechanotransduction]. PMID- 8217410 TI - [A family with Menzel's disease showing dementia and various extrapyramidal symptoms]. AB - Recent progress in neurology has revealed that hereditary olivo-ponto-cerebellar atrophy (OPCA) is in fact three different diseases. These are Menzel's disease, in which degeneration in the olivopontocerebellar (OPC) system is quite severe and similar to that of the patient described by Menzel in 1891, spinocerebellar ataxia 1 (SCA 1), in which the gene locus exists in the short arm of chromosome 6, and hereditary OPCA with retinal degeneration. We present a family with Menzel's disease, some of whom showed dementia and various extrapyramidal symptoms including tremor, myoclonus, and choreoathetoid involuntary movement. MATERIALS: This dominant hereditary cerebellar ataxia family had five affected members in four generations. Neuropathological examination of one member (Case 3) revealed Menzel's disease. There was severe degeneration in the OPC system, the substantia nigra, Clarke's column, the posterior column, and the anterior horn of the spinal cord, and slight-to-moderate degeneration in the globus pallidus and subthalamic nucleus. However, the dentate nucleus, spinocerebellar tracts, and oculomotor nucleus including the medial longitudinal fasciculus were spared. The brain weight was 990 g. Case 1 (Case 3's grandmother) developed slowly progressive ataxia at the age of 55. She showed no involuntary movement or dementia. She died at 63 years of age. Case 2 (Case 3's mother) developed ataxia at 42 years of age, followed by tremor of the hands and head, and died at age 57. She did not show dementia. Case 3 (the autopsied case) developed progressive ataxia at 27 years of age, followed by mental deterioration, tremor, myoclonus, and generalized amyotrophy and sensory disturbance during her fifth decade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217411 TI - [Ossification and calcification of the cervical ligamentum flavum--case reports]. AB - Ossification of ligamentum flavum was reported usually lower thoracic and lumbar region, and rarely seen in the cervical region. Calcification of cervical ligamentum flavum is also relatively rare. We report a case of ossification and another of calcification of cervical ligamentum flavum, and discussed the difference of the clinical and radiological features in these conditions. Case 1: A 55-year-old man presented with numbness of the left shoulder and urinary dysfunction. Neurological examination revealed weakness, muscle atrophy and elevated deep tendon reflexes of the left extremities. CT showed ossified mass protruding into the right side of the canal and compressing the spinal cord at C 3/4 and C 4/5. MRI showed low intensity mass both on T1- and T2-weighted images and severe compression of the spinal cord. Left side partial hemilaminectomy with foraminotomy, so called "key hole" foraminotomy, satisfactorily decompressed the cord with clinical improvement. Case 2: A 70-year-old woman complained numbness of both hands for two years. She had sensory disturbance of both hands and spastic gait disturbance. Cervical X-ray films showed calcified nodules on the inner surface of lamina at C4/5. Axial CT demonstrated calcification in the ligamentum flavum at the C4/5 and C5/6 levels. MRI showed posterior spinal cord compression at the C4/5 and C5/6 levels. Osteoplastic laminotomy and removal of the affected ligamentum flavum were performed with successful result. Only 8 cases ossification of cervical ligamentum flavum above C6/7 have been so far reported. All are Japanese; four male and four female cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217412 TI - [Type II citrullinemia triggered by acetaminophen]. AB - We report a 19-year-old man with type II citrullinemia triggered by the administration of acetaminophen when he caught a cold. He was admitted to our hospital of impairment of consciousness and abnormal behaviors. On admission he was comatose and laboratory data revealed respiratory alkalosis which was probably induced by hyperammonemia. Liver dysfunction was mild. Plain CT scans showed brain edema, and EEG revealed triphasic waves. Analysis of plasma and urine amino acids showed a significant increase in citrulline and the activity of argininosuccinate synthetase was markedly reduced in a liver biopsy specimen. Histopathology of the liver revealed inflammatory changes which was probably induced by acetaminophen. Branched chain amino acids transfusion was effective for consciousness disturbance, and sodium benzoate was effective for hyperammonemia. We reviewed 28 patients reported in the literature from 1981 to 1992 to evaluate the probable triggering episodes in type II citrullinemia. Four categories of probable trigger were found, which included 1) stress, 2) liver dysfunction, 3) alcohol, and 4) drugs. Avoidance of these triggers, early diagnosis, and treatment seem most important for the good prognosis and the quality of life. PMID- 8217413 TI - [Neurinoma of the cauda equina associated with normal pressure hydrocephalus]. AB - Hydrocephalus associated with spinal tumors is a well known but not common phenomenon. Over 80 such cases have been reported since 1931 by Kirieleis. Most of those cases present features of raised intracranial pressure, for instance papilledema. The histological diagnosis of the tumors is ependymoma (1/2), neurinoma (1/4) and malignant astrocytoma (1/4). On the other hand dementia as a symptom of spinal tumors has been reported only 13 times. In 11 of 13 cases presented with signs of NPH, mental status improved only by removal of the tumors without shunt operation. The histological diagnosis of the tumors is neurinoma (9 cases), ependymoma (2) and meningioma (2). Ours is the 14th case. A 59-year-old woman presented a 6 month history of memory disturbance, gait disturbance and urinary incontinence. CT scan showed ventricular dilatation. RI cisternography revealed a block at lumbar region. CSF obtained by lumbar puncture was deep yellow and turbid. CSF protein level was markedly elevated to 4073 mg/dl. MRI of the spinal cord demonstrated cauda equina mass. Total removal of the spinal tumor was performed. The histological diagnosis was neurinoma. Within 3 weeks the patient's symptoms had dramatically improved. The decrease in ventricular size was noted on CT 18 months after operation. We think one of the most important factors by which spinal tumors develop NPH is elevation of the CSF protein content. In our case, postoperative protein level decreased from 4073 to 274 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217414 TI - [Regional phacomatosis with cerebral AVMs and cavernous hemangioma of the skull- report of a case]. AB - We report the coexistence of multiple arteriovenous malformations (AVMs) and hemangioma of the skull in a 38-year-old man with associated varicose veins in his scalp. The patient also had hypotrophy of all right limb tissues with skin pigmentation and syndactyly of both feet. CT scans revealed intraventricular hemorrhage and a hemangioma of the skull at the posterior fossa. Because of the location of the arteriovenous malformations, surgical evacuation and resection were not attempted. The hemangioma was totally removed to decompress the posterior fossa. A few cases of regional phacomatosis with intracranial AVMs have been reported, but we could not find a report of the coexistence of intracranial multiple AVMs and hemangioma of the skull with associated varicose veins of the scalp and skeletal hypotrophy. We discuss on the etiology of the coexistence of regional phacomatosis and hemangioma and on the difference between our case and typical regional phacomatosis. PMID- 8217415 TI - [A 47-year-old woman with meningeal signs and consciousness disturbance]. AB - We report a 47-year-old woman with SLE, who developed meningeal signs and consciousness disturbance. She noted an onset of fever, and swelling and pain in her face, hands and feet in 1990. She was seen in another hospital and the diagnosis of SLE was made. She was treated with prednisolone with marked improvement in her symptoms. She was well with 5 mg of oral prednisolone daily until January of 1991, when she developed fever, myalgia and weakness in her legs. She was admitted to the medical service of our hospital on August 5. She was receiving 15 mg of prednisolone daily. Gram positive rods were cultured from her blood on August 5. She became incoherent 2 days later, and had a convulsive episode on August 8. After the convulsion, she lost consciousness from which she did not recover. Her CSF contained 304/3 microliters cells, 29 of which were neutrophils, 6 lymphocytes, 90 others, and 179 destructed cells. The CSF protein content was 345 mg/dl, and glucose 23 mg/dl. A neurological consultation was asked on August 9. Physical examination at that time revealed a semicomatous woman. Respiration was 30/min and regular. BP 132/82 mmHg, heart rate 122/min and regular, and BT 39.6 degrees C. General physical examination was unremarkable. Pertinent neurologic findings were positive Kernig sign and spasticity in all four limbs. Brain stem reflexes were retained. Upon painful stimulation, withdrawal response was elicited both lower extremities. She was treated with pipiracillin, latamoxef and phenobarbital, however, she had frequent seizures. She was deeply comatose on December 10. She became flaccid and no more meningeal signs were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217416 TI - Infection control in dentistry. A practitioner's guide. British Dental Association. PMID- 8217417 TI - Can we afford the welfare state? PMID- 8217418 TI - Cross-infection control. PMID- 8217419 TI - Delusion of having AIDS. PMID- 8217421 TI - Vocational training. PMID- 8217420 TI - Gingival enlargement in a patient medicated with amlodipine. PMID- 8217422 TI - 'Deafness and dentistry'. PMID- 8217423 TI - Are intraligamentary injections intravascular? AB - A pressure type syringe was used to give intraligamentary injections (IL) to upper teeth of two formulations commonly used in general practice, lignocaine and prilocaine. Assay of plasma levels of drug was carried out by high performance liquid chromatography. Results of assays after intraligamentary injections were then compared with results of assays after intravenous injections of plain drug in the same subjects. Both formulations of local anaesthetic were found as peak levels in the circulation, presumably after intraosseous spread, by 2 minutes following the intraligamentary injections. For lignocaine the peak amount was nearly 7% of the intravenous dose and for prilocaine the peak amount was 25% of the intravenous dose, at 2 minutes after injection. It was concluded that IL injections for healthy adults were unlikely to cause systemic unwanted effects when given in small doses. PMID- 8217424 TI - Occupational stress factors in hospital dentists. AB - This investigation examined perceived stress levels, personality characteristics and stress outcomes in a group of hospital dentists working in Belfast. Mean scores for this group were also compared with normative values. The occupational stress indicator was distributed to 45 hospital dentists; 40 returned the completed questionnaire. The mean score for each stress-related factor was analysed and compared with normative values. In addition the ranked scores for sources of stress were examined, and no significant differences could be demonstrated between the two groups. However, for external locus of control this group of hospital dentists demonstrated a significantly higher mean score of 42.3 than the mean normative value of 38.6. The dentists' score for their perception of their state of physical ill health was 23.9 and was significantly lower than the normative value of 27.8 but no differences could be demonstrated between the groups for mental health, Type A personality or mean stress levels. PMID- 8217425 TI - La maladie du petit papier. AB - La maladie du petit papier is the term given when patients relate their bodily complaints, with written lists. Sixteen patients with orofacial complaints attending with lists were studied. Eighty per cent were females and most had chronic oral discomfort. Many had several complaints and had sought multiple opinions. In none was evidence of an organic basis for their main complaint detectable, but this must always be thoroughly excluded. PMID- 8217426 TI - Gingival swelling as a manifestation of non-Hodgkin's lymphoma. AB - A case is reported in which a 52-year-old male patient presented to his dental practitioner with several unusual, purple coloured gingival swellings, the largest of which was about 1 cm in diameter. A careful medical history revealed that the patient had 2 years previously been diagnosed as having low-grade non Hodgkin's lymphoma (NHL). Prompt referral led to confirmation of the provisional diagnosis of gingival manifestation of NHL and early institution of appropriate treatment. PMID- 8217427 TI - Oral problems associated with CREST syndrome: a case report. AB - A patient with CREST syndrome is described, with such severe limitation of mouth opening that extractions were required before upper gastrointestinal endoscopy could be performed. Features of CREST syndrome of importance to the dental and oral surgeon are described. PMID- 8217428 TI - A review of the Eastman Dental Practice Centre. AB - Early last year I found myself looking back over 19 enjoyable years in general dental practice. I certainly had not let the grass grow under my feet, as I had taken courses and kept up with developments. I was providing my patients with good care but I could not help wondering, 'Could I enjoy this even more? Could my standard of care to patients be better still?' PMID- 8217429 TI - A tooth ablation custom occurring in the Maldives. AB - Not many people would willingly have their teeth drastically filed, ground, chipped away, or even extracted without the use of an anaesthetic. Even fewer would consent to the treatment if the teeth to be involved were the upper incisors and were entirely healthy. The practice of tooth mutilation or ablation has, however, been carried out worldwide since prehistoric times. PMID- 8217430 TI - Retrenching a pocket at a time. PMID- 8217431 TI - The nature and use of nursing diagnosis in hospitals. AB - This descriptive study examined the frequency of types of diagnoses formulated by RNs. Ten patient charts were randomly selected from each of 10 frequently occurring diagnosis-related groups (DRGs) (N = 100). Findings indicated the majority of diagnoses (N = 1,504) were made in the Exchanging (55.33%) Human Response Pattern by two groups of nurse raters--RN caregivers and CNSs. Differences in number of diagnoses made by the nurse groups were statistically significant for all Human Response Patterns. Overall, the CNSs made more diagnoses than the caregivers (944 vs. 560), and their diagnoses were of a broader nature. PMID- 8217432 TI - New diagnosis: interrupted breastfeeding. AB - Interrupted breastfeeding was approved by the membership to be added to the NANDA taxonomy in 1992. The diagnosis was developed to name the response that occurs when a breastfed baby cannot be put to breast for some or all of the feedings. Two examples of life processes/events, premature or sick infant and maternal employment, illustrate the application and use of the diagnosis. Nursing interventions for each situation are discussed. A comparison describing the differences between interrupted breastfeeding and ineffective breastfeeding is included to address the controversy of whether or not the diagnoses are the same. A sample diagnosis/care plan is added to demonstrate use of the diagnoses in clinical practice. PMID- 8217433 TI - Keeping it simple. PMID- 8217434 TI - Noncompliance revisited: a disciplinary perspective of a nursing diagnosis. AB - One of the nursing diagnoses accepted by NANDA is noncompliance. However, this diagnosis has been criticized because it implies coercion and dominance by health professionals, and because of the negative stereotyping the term promotes. The authors argue that noncompliance should not be used as a nursing diagnosis because of incongruence with nursing history, philosophy, ethics, theory, and the need for clinical utility of diagnoses. Alternative diagnoses are proposed. PMID- 8217435 TI - You make the diagnosis: case study. The challenge of ostomy care at home. PMID- 8217436 TI - Dual chamber pacing for hypertrophic obstructive cardiomyopathy: has its time come? PMID- 8217437 TI - Antiarrhythmic drugs in the management of atrial fibrillation. PMID- 8217438 TI - Myocardial perfusion in humans: what can we measure? PMID- 8217440 TI - High frequency rotational ablation: an alternative in treating coronary artery stenoses and occlusions. AB - OBJECTIVE: To prove the safety and effectiveness of high frequency rotational ablation of coronary artery stenoses and occlusion in humans. SUBJECTS: 106 patients with symptoms (91 men, 15 women) who had 67 significant stenoses, mainly types B and C, and 46-chronic occlusions. MAIN OUTCOME MEASURES: Mean change in diameter stenosis after rotational angioplasty alone and in combination with percutaneous transluminal coronary angioplasty immediately after treatment and 24 hours and six months later; restenosis rates at six months; complication of treatment. RESULTS: Rotational ablation could not be used in five stenoses and 16 chronic occlusions because of inability to reach or cross the lesion with the Rotablator guide wire. In four cases rotational ablation failed. Initial angiographic and clinical success by rotational ablation was achieved in 40 of the 67 stenoses (60%) and in 18 of the 46 chronic occlusions (39%). Additional balloon angioplasty was performed in 45 patients, increasing the success rates to 79% and 54%, respectively. In the 62 stenoses treated by rotational ablation the angiographic diameter stenoses were reduced from 76% (SD 14%) to 32% (14%) after Rotablator treatment alone and from 75% (11%) to 33% (17%) with additional balloon angioplasty. In the 30 chronic occlusions treated by rotational ablation the angiographic diameter stenoses were reduced to 38% (18%). At six months angiographic restenosis was evident in nine of the 25 (36%) stenoses treated with rotational ablation alone, in seven of the 22 (32%) stenoses treated with rotational and balloon angioplasty, and in 14 of the 24 (58%) chronic occlusions. There were no procedural deaths and two patients (2%) underwent emergency coronary artery bypass grafting. Although no transmural infarction occurred, there were five (6%) non-Q wave infarctions (two embolic side branch occlusions, two subacute occlusions, and one acute occlusion). Clinically insignificant slight increases in creatine kinase activity were seen in five patients (6%). Severe coronary artery spasm unresponsive to medical treatment was provoked in seven cases (8%). CONCLUSIONS: High frequency rotational ablation is a safe and effective method for treating type B and C coronary artery lesions with results comparable to percutaneous transluminal coronary balloon angioplasty. The combined use of rotational ablation and balloon angioplasty is feasible and is necessary in about half of all procedures, in most cases because the lumen created by the biggest burr is too small. PMID- 8217439 TI - Magnetic resonance imaging of coronary arteries: technique and preliminary results. AB - BACKGROUND: Coronary artery imaging is an important investigation for the management of coronary artery disease. The only reliable technique presently available, x ray contrast angiography, is invasive and is associated with a small morbidity and mortality. Alternative non-invasive imaging would be useful, but the small calibre and tortuosity of the coronary vessels, and cardiac and respiratory motion create formidable imaging problems. OBJECTIVE: The development of rapid magnetic resonance imaging of the coronary arteries. PATIENTS: 21 healthy controls and five patients with coronary artery disease established by x ray contrast angiography, of whom two had undergone bypass grafting. METHODS: Magnetic resonance imaging was performed with gradient echoes and a segmented k space technique, such that a complete image was acquired in 16 cardiac cycles during a breathhold. The signal from fat was suppressed and images were acquired in late diastole to reduce artefact from cardiac motion. An imaging strategy was developed for the proximal arteries, including longitudinal imaging from oblique planes defined according to the origins and the continuation of the arteries in the atrioventricular grooves or interventricular sulcus. RESULTS: Of the 26 subjects studied, 22 were imaged successfully. Identification of the artery was possible for the left main stem, left anterior descending, right coronary, and left circumflex arteries respectively in 95%, 91%, 95%, and 76%. The arterial diameter at the origin could be measured in 77%, 77%, 81%, and 63%. The mean (SD) arterial diameter in each case (4.8 (0.8), 3.7 (0.5), 3.9 (0.9), and 2.9 (0.6) mm) was not significantly different from reference values. The mean length of artery visualised was 10.4 (5.2), 46.7 (22.8), 53.7 (27.9), and 26.3 (17.5) mm. In 12 healthy men the total coronary area was 30.9 (9.2) mm2 and the ratio compared with body surface area was 16.4 (4.4) mm2m2 (both p = NS compared with reference values). In seven patients in whom x ray contrast coronary angiography was available, the proximal arterial diameter was 3.9 (1.1) mm measured by magnetic resonance and 3.7 (1.0) mm by x ray contrast angiography (p = NS). The mean difference between the measurements was 0.2 (0.5) mm, and the coefficient of variation was 13.7%. All five occluded coronary arteries were identified, as were all three vein grafts. In two patients insertion of the graft into the native arteries was identified. CONCLUSIONS: Magnetic resonance coronary angiography is feasible. Good results were obtained by a breath-hold, fat suppression technique, gated to late diastole. Arterial occlusions and vein grafts were readily identified. Further studies are required to establish its value in the detection of coronary stenosis and to develop the measurement of coronary flow velocity which could be used to quantify the severity of the stenosis. PMID- 8217441 TI - Prognostic significance of transient ST segment changes after coronary artery bypass surgery: a long-term (4-10 year) follow up study. AB - OBJECTIVE: To assess the long-term (four to 10 years) prognostic significance of transient ST segment changes on ambulatory ST segment monitoring after coronary artery bypass grafting (CABG). PATIENTS AND METHODS: 76 patients (67 men, nine women) underwent CABG between 1982 and 1984 (n = 31) and between 1987 and 1988 (n = 45) and at a mean age of 57. All underwent 48 hours of ambulatory ST segment monitoring at a mean of 19 weeks after surgery. The results were available for assessment. All general practitioners were contacted and patients' notes reviewed. Patients were contacted by telephone. Details were recorded of intervening events (acute myocardial infarction, unstable angina, need for further revascularisation, and deaths). Event free survival curves were produced for those with and without transient ST segment changes during routine postoperative ambulatory ST segment monitoring. RESULTS: During 3213 hours of monitoring after CABG, 21 (27.6%) of 76 patients had transient ST segment changes, of which 70% were silent. Over a mean 70 month follow up period, patients with such ischaemic changes were no more likely to have either an objective (myocardial infarction or cardiac death) or subjective (unstable angina or another revascularisation) event than those patients without ischaemic changes. This finding was the same in patients operated on between 1987 and 1988 and between 1982 and 1984. CONCLUSIONS: Although ambulatory ST segment monitoring is becoming increasingly popular in some countries as a routine investigation for ischaemia in various coronary subgroups, the findings of such an investigation, when performed after CABG, do not help to identify a subgroup more likely to have an adverse outcome during up to 10 years of follow up. There seems to be no reason to perform this investigation after surgery, and particularly to refer patients for reinvestigation because of the detection of predominantly silent ST segment changes of uncertain relevance. PMID- 8217442 TI - Disease of the left main coronary artery: early surgical results and their association with carotid artery stenosis. AB - OBJECTIVES: To review the results of surgical revascularisation for left main coronary artery stenosis and the associated vascular pathology that is responsible for cerebrovascular complication. PATIENTS: 60 patients (45 men, 15 women) (mean age 61.3 (39-79)) who underwent revascularisation for stenosis of the left main stem coronary artery (LMS) between January 1987 and August 1990 were compared with an age and sex matched control group of patients undergoing revascularisation for triple vessel disease during the same period. OUTCOME MEASURES: In-hospital morbidity and operative mortality. RESULTS: 24 patients in the LMS group presented with unstable angina. The left ventricular ejection fraction was less than 50% in 30 patients and less than 30% in nine. 17 patients (28%) had large vessel extracranial carotid artery disease and 10 patients had vascular disease of the lower limbs. In six patients atheromatous plaques were noted in the ascending aorta during surgery. There was no in-hospital mortality. In-hospital morbidity included neurological deficits in five (8.3%), arrhythmias in seven (11.6%), and pulmonary complications in six (10%) patients. The incidence of carotid artery disease in the LMS group was significantly higher (p = 0.04). Atheromatous plaque in the ascending aorta and postoperative neurological complications were more common patients with LMS. CONCLUSIONS: The incidence of carotid artery disease was higher and postoperative cerebrovascular complications were more common in patients who had coronary artery revascularisation for stenosis of the left main stem coronary artery. The early surgical results were excellent. These findings suggest that for optimum perioperative management patients with stenosis of the left main coronary artery should be screened for carotid artery disease before bypass surgery. PMID- 8217444 TI - Distinguishing between acute and subacute massive pulmonary embolism by conventional and Doppler echocardiography. AB - OBJECTIVE: To determine the ability of conventional and Doppler echocardiography to distinguish between minor, acute massive, and subacute massive pulmonary embolism in patients with confirmed pulmonary embolism. DESIGN: Prospective study of a consecutive series of 47 patients with confirmed pulmonary embolism. SETTING: Department of internal medicine, university clinic. PATIENTS: 11 patients (23%) had minor, 23 patients (49%) had acute massive, and 13 patients (28%) had subacute massive pulmonary embolism. RESULTS: Dilatation of the right ventricular cavity (33 (92%)) and asynergy of the right ventricular free wall (29 (81%)) were seen only in patients with acute and subacute massive pulmonary embolism (n = 36). 23 (64%) with pulmonary hypertension had tricuspid regurgitation. The velocity of the tricuspid regurgitant jet correlated with the pulmonary arterial pressure (r = 0.88, SEE = 11.6 mm Hg) and was significantly lower in patients with acute massive pulmonary embolism (3.0 (0.4) m/s, n = 12) than in patients with subacute massive pulmonary embolism (4.2 (0.6) m/s; n = 11) (p < 0.001). The use of predefined indices (right ventricular free wall thickness > 5 mm; tricuspid regurgitant jet velocity > 3.7 m/s; and the occurrence of both a dilated right ventricular cavity with normal interventricular septal motion, or an inspiratory collapse of the inferior vena cava, or both) correctly identified 11 of 13 patients (85%) with subacute massive pulmonary embolism. CONCLUSION: Conventional and Doppler echocardiography were successful in evaluating the haemodynamic consequences of pulmonary embolism. PMID- 8217443 TI - Clinical presentation and functional prognosis in syndrome X. AB - OBJECTIVES: To assess the effect of clinical presentation on functional prognosis in patients with syndrome X. DESIGN: A prospective study. Patients with syndrome X presenting with unstable angina and stable angina were followed up with a questionnaire to examine their functional state. PATIENTS: 41 patients with syndrome X and unstable angina and 41 patients with syndrome X and stable angina. Syndrome X was defined as typical anginal chest pain, a positive exercise test, and normal coronary angiogram. SETTING: Regional cardiothoracic centre. RESULTS: The mean follow up time was 36 (range 20-51) months for the unstable angina group and 35 (range 19-51) months for the stable angina group. No patient was lost to follow up in either group. At follow up 28 patients in the unstable angina group were pain free compared with 15 patients in the stable angina group (p = 0.008). Seven patients in the unstable angina group had further hospital admission with chest pain after the cardiac catheterisation compared wtih 12 patients in the stable angina group (NS). Seven patients in the unstable angina group believed that they had heart disease compared with 27 in the stable angina group (p < 0.001). 26 patients in the unstable angina group but only eight patients in the stable angina group were unlimited in their physical activity (p < 0.001). 12 patients in the unstable angina group compared with 27 patients in the stable angina group were unable to work normally because of chest pain (p < 0.001). The mean (SD) duration of symptoms before cardiac catheterisation was 7.9 (4.7) months in the unstable angina group and 13.4 (5.6) months in the stable angina group (p < 0.001). 10 patients in the unstable angina group and 24 patients in the stable angina group still attended hospital outpatient clinics because of chest pain (p = 0.004). 16 patients in the unstable angina group and 29 patients in the stable angina group were still taking regular antianginal medication (p < 0.001). CONCLUSIONS: Patients with syndrome X who present with unstable angina have a significantly better functional prognosis than those presenting with symptoms of stable angina. This may reflect differences in underlying pathophysiological mechanisms. PMID- 8217445 TI - Pathogenesis of oedema in chronic severe anaemia: studies of body water and sodium, renal function, haemodynamic variables, and plasma hormones. AB - BACKGROUND: Patients with chronic severe anaemia often retain salt and water. Fluid retention in these patients is not caused by heart failure and the exact mechanisms remain unclear. This study was designed to examine some of the possible mechanisms. METHODS AND RESULTS: Haemodynamic variables, body fluid compartments, renal function, and plasma hormones were measured in four patients with oedema caused by chronic severe anaemia (mean (SE) haematocrit 13 (1.7)) who had never received any treatment. Cardiac output was increased (6.1 (0.6) l/min/m2) and right atrial (7.8 (1) mm Hg), mean pulmonary arterial (20.5 (2.0) mm Hg), and mean pulmonary arterial wedge (13 (2.7) mm Hg) pressures were slightly increased. The mean systemic arterial pressure (81 (1.3) mm Hg) and systemic vascular resistance (12.3 (1.1) mm Hg x min x m2/l were low. There were significant increases in total body water (+14%), extracellular volume (+32%), plasma volume (+70%), and total body exchangeable sodium (+30%). Renal blood flow was moderately decreased (-46%) and the glomerular filtration rate was slightly reduced (-24%). There were significant increases in plasma noradrenaline (2.1 fold), renin activity (15-fold), aldosterone (3.2-fold), growth hormone (6.3 fold), and atrial natriuretic peptide (12-fold). CONCLUSION: In patients with oedema caused by chronic severe anaemia there is retention of salt and water, reduction of renal blood flow and glomerular filtration rate, and neurohormonal activation similar to that seen in patients with oedema caused by myocardial disease. However, unlike patients with myocardial disease, patients with anaemia have a high cardiac output and a low systemic vascular resistance and blood pressure. It is suggested that the low concentration of haemoglobin in patients with anaemia causes a reduced inhibition of basal endothelium-derived relaxing factor activity and leads to generalised vasodilatation. The consequent low blood pressure may be the stimulus for neurohormonal activation and salt and water retention. PMID- 8217447 TI - Prostacyclin (epoprostenol) and heart-lung transplantation as treatments for severe pulmonary hypertension. AB - OBJECTIVE: To determine whether epoprostenol (prostacyclin, PGI2) or heart-lung transplantation (HLT), or both improves survival of patients with severe pulmonary hypertension. DESIGN: This was a prospective study where the effects of epoprostenol were compared with conventional treatment. Also, the benefits of epoprostenol and HLT were assessed by comparing survival in this group with that of 120 patients at the Mayo Clinic before HLT and epoprostenol treatment became available. PATIENTS AND INTERVENTIONS: Forty four patients were studied; 25 received continuous epoprostenol over a four year period (mean (SD) cardiac index 1.8 (0.4) 1 min-1 m-2 and mean (SD) pulmonary artery pressure (PAP) 70 (16) mm Hg) and 19 did not (cardiac index 2.1 (0.6) 1 min-1 m-2 and PAP 64 (13) mm Hg). Ten patients underwent HLT: seven had received epoprostenol, and three had not. RESULTS: The therapeutic intervention with epoprostenol, or HLT, or both improved survival compared with the Mayo clinic patients (p = 0.05). Most of the benefit was conferred by epoprostenol, which prolonged survival twofold from a median time of eight to 17 months and doubled the changes of successful HLT. The improved survival with epoprostenol was not related to its immediate capacity to cause pulmonary vasodilation. Those patients who had limited acute pulmonary vasodilation when treated with epoprostenol showed the greatest improvement in survival. CONCLUSIONS: These preliminary results indicate that those pulmonary hypertensive patients with the poorest chance of survival can be helped by epoprostenol and by HLT. PMID- 8217446 TI - Lack of circadian rhythm of plasma concentrations of vasoactive intestinal peptide in patients with orthotopic heart transplants. AB - OBJECTIVE: To study the circadian pattern of plasma concentrations of vasoactive intestinal peptide (VIP) in patients with orthotopic heart transplants. Circulating VIP is known to have neural and immunological sources. PATIENTS AND METHODS: 13 patients with orthotopic heart transplants were studied 12-53 months (mean 31.8 months) after operation. All were haemodynamically compensated and had no histological evidence of rejection. They were being treated with cyclosporin, azathioprine, and prednisone. Ten healthy individuals were studied as controls. Circulating VIP was assayed six times within a 24h period. Time qualified data were analysed by ANOVA and the cosinor method. Student's t test for unpaired data and Bingham's test for cosinor-derived parameters were used for statistical comparisons. RESULTS: Plasma concentrations of VIP were lower in the patients with orthotopic heart transplants than in the controls (p < 0.001). ANOVA and the cosinor method respectively showed a statistically significant within-day variability and circadian rhythm in the controls but not in the patients with heart transplants. DISCUSSION: The low plasma concentrations of VIP in the patients with heart transplants could be the result of the lack of contribution by the cardiac VIPergic fibres, a reduction of VIP release by the pharmacologically suppressed immune system, the inhibitory effects of cyclosporin on neural function and humoral secretions, and the effects of negative feedback on VIP release of high concentrations of atrial natriuretic peptide. The lack of the circadian rhythm suggests a structural disorder, which should be further investigated. PMID- 8217448 TI - Sinus node dysfunction during long-term lithium treatment. AB - BACKGROUND AND OBJECTIVE: Lithium has occasionally been reported to cause symptomatic sinus node bradyarrhythmias. The prevalence and mechanism of these arrhythmias during long-term treatment are unknown. The aims of this study were (a) to evaluate the systemic effects of lithium treatment on cardiac conduction in individuals who were free from cardiovascular disorders; (b) to assess the prevalence of lithium treatment in a group of patients with pacemakers; and (c) to evaluate the interaction between the parasympathetic limb of the autonomous nervous system and the sinus node cells during long-term lithium treatment. PATIENTS AND METHODS: 45 patients who had been treated with lithium for > 12 months were investigated in a long-term electrocardiography study. Only patients without cardiovascular disease, or concomitant chronotropic medication, or metabolic disorders known to cause rhythm disturbances were included. An age stratified population was used as a reference group. 21 patients also underwent analysis of carotid sinus pressure and sinus cycle length before and after atropine to clarify whether neural mechanisms were involved. The prevalence of lithium treated patients was determined in 650 patients with pacemakers. RESULTS: (a) Signs of moderate sinus node dysfunction (sinus arrest > 1.5 s, minimum heart rate < 50 beats/min) were found in 56% and 78% respectively in the lithium treated group compared with 30% and 30% respectively in the reference group (p < 0.01). Severe sinus node dysfunction was equally common in both groups. (b) The prevalence of chronic lithium treatment in the pacemaker population was 0.46%. (c) Sinus cycle variations were abnormal in the basal state in three (14%) patients and in 11 (52%) patients after atropine despite signs of intact and normal parasympathetic innervation. CONCLUSIONS: Depressed sinus node function was significantly more common in a lithium-treated population than in an age stratified reference group. Clinically significant dysfunction, however, was uncommon. The effect of lithium on the sinus node seemed to be intrinsic and was not caused by increased parasympathetic tone. PMID- 8217449 TI - Prevalence of toxoplasma myocarditis in patients with the acquired immunodeficiency syndrome. AB - OBJECTIVE: To evaluate the prevalence of cardiac toxoplasmosis in a series of 182 necropsies performed between 1987 and 1991 on patients infected with the human immunodeficiency virus (HIV), to correlate this prevalence with the ante mortem diagnosis of cardiac involvement, and to assess the role of such cardiac lesions in the immediate cause of death. PATIENTS AND METHODS: Complete necropsies of 182 HIV-infected patients (48 women, 134 men) were performed consecutively between 1987 and 1991. Risk factors, identified in 174 cases, included drug abuse (111/182), homosexuality (51/182), and blood transfusions (12/182). 16 samples were systematically obtained from each heart for histological study. If trophozoites or lymphocytic myocarditis were seen, immunohistochemical investigations were carried out with polyclonal antibodies for Toxoplasma gondii. An ultrastructural study was performed in four patients with toxoplasma myocarditis. Myocardial lesions were defined by the Dallas classification. Clinical data (and information on electrocardiograms and echocardiograms) were obtained from medical records. RESULTS: Cardiac toxoplasmosis was diagnosed at necropsy in 21 (12%) patients. Cardiac lesions were associated with toxoplasmic encephalitis in 18 patients and were solitary in three patients. Acute diffuse myocarditis was present in 6/21, rare foci of myocarditis were seen in 8/21, and intramyocytic toxoplasmic cysts without any inflammatory reaction or necrosis were seen in 4/21. Anti-toxoplasma immunolabelling showed cardiac toxoplasmosis in three patients with lymphocytic myocarditis. Particles with the ultrastructural characteristics of Toxoplasma gondii trophozoites were seen in four cases. Six patients had presented with cardiac symptoms, confirmed by electrocardiographic and echocardiographic abnormalities during their disease course, and their cardiac lesions were directly responsible for the death. CONCLUSION: Cardiac toxoplasmosis was common in this necropsy series of HIV infected patients. Cardiac toxoplasmosis had been suspected clinically in four patients. Myocardial lesions were generally asymptomatic and were not discovered until necropsy. Solitary cardiac involvement was not uncommon reflecting parasite reactivation at a myocardial site. The incidence of cardiac toxoplasmosis in this group of immunodepressed subjects from an area with a high prevalence of this parasitic disease justifies regular follow up of such patients by electrocardiography and echocardiography as well as immediate administration of anti-toxoplasma treatment should sudden heart failure occur. PMID- 8217451 TI - Multiple arterial stenoses of unknown aetiology in the coronary, cerebral, and brachial arteries. AB - A 13 year old girl with multiple arterial stenoses of unknown aetiology is described. At the age of seven months she was noted to have cardiomegaly and diminished left ventricular ejection fraction with no cardiac anomaly. Cardiac function gradually improved and her condition remained satisfactory until she was 11 years old when multiple lesions in the coronary, cerebral, and left brachial arteries were diagnosed. Histological examination of an endomyocardial biopsy specimen from the right ventricle showed hypertrophic muscles surrounded by abundant fibrous tissue. Percutaneous transluminal angioplasty of the right coronary stenoses led to complete occlusion. PMID- 8217450 TI - Tissue plasminogen activator (alteplase) treatment for femoral artery thrombosis after cardiac catheterisation in infants and children. AB - OBJECTIVE: To determine the efficacy of fibrinolytic therapy with tissue plasminogen activator (alteplase) in infants and children with arterial thrombosis after cardiac catheterisation. DESIGN: Use of alteplase (Actilyse) in a protocol with prospective data collection. Alteplase was administered to infants and children with arterial thrombosis after cardiac catheterisation. A dose of 0.5 mg/kg/h was given continuously via a peripheral vein for the first hour followed by 0.25 mg/kg/h till clot lysis occurred or treatment had to be stopped because of bleeding complications. SETTING: University hospital, intensive care unit. PATIENTS: 17 consecutive infants and children with femoral artery thrombosis after cardiac catheterisation between 1 April 1988 and 31 October 1991. MAIN OUTCOME MEASURE: Reopening of the vessel. RESULTS: Complete clot lysis was achieved in 16 of 17 patients within 4-11 hours after the start of treatment. In one patient only partial lysis occurred. After complete lysis rethrombosis developed in one patient 15 hours after the end of treatment. Bleeding complications were seen in nine patients. These were restricted to the arterial puncture site, except for one who showed mild epistaxis. Three patients had to be treated with packed erythrocytes. CONCLUSIONS: Alteplase was an effective treatment of arterial thrombosis after cardiac catheterisation in infants and children. Further studies are needed to determine whether lower doses will reduce the frequently observed bleeding complications. PMID- 8217452 TI - Atypical ventricular tachycardia and syncope with left coronary artery origin from the right coronary sinus. AB - An 18 year old man suddenly lost consciousness while jogging. The ambulance crew documented atypical ventricular tachycardia and an episode of ventricular fibrillation. Coronary angiography showed the left main coronary artery arising from the right sinus of Valsalva. Subsequent surgical coronary revascularisation was successful. PMID- 8217453 TI - Traumatic rupture of the thoracic aorta diagnosed by transoesophageal echocardiography. AB - Transoesophageal echocardiography is a safe and rapid means of obtaining anatomical and dynamic information about the descending aorta. It was used to confirm a suspected diagnosis of ruptured descending aorta. PMID- 8217454 TI - Congenital muscular torticollis: long-term follow-up of thirty-eight partial resections of the sternocleidomastoid muscle. AB - Thirty-eight patients with muscular torticollis were treated by a partial resection of the sternocleidomastoid muscle between 1970 and 1981. Clinical evaluations were performed on 35 of these patients who were followed up for 10 years (average of 11.3 years). Of 31 patients under 5 years of age at operation, good results according to Canale's criteria were obtained in 28 (90%). In four patients aged 6 years or more at operation, three showed good results. Postoperatively, massive cotton bandaging was applied with the neck in the neutral position for 3 weeks. A plaster cast, brace, or physiotherapy involving active motion training was not necessary. PMID- 8217455 TI - Influence of pelvic osteotomy on birth canal size. AB - Six pelvic osteotomies (Salter, Sutherland, Steel, Tonnis, Chiari, and periacetabular) were performed on the right hemipelvis of adult female pelvic plastic models. Each pelvis underwent conventional X-ray and computed tomographic digital pelvimetry before and after osteotomy. The change in the anteroposterior and transverse dimensions at the inlet, midpelvis, and outlet were calculated. None of the osteotomies significantly decreased the inlet. The Salter and Sutherland osteotomies decreased the midpelvis to borderline low. The Salter, Sutherland, and Steel osteotomies significantly decreased the pelvic outlet. These changes correlated closely with those in living patients. Much of this decrease is nullified when the osteotomy is performed prior to the pubertal growth spurt. PMID- 8217456 TI - How safe are ceramic heads as hip endoprostheses? A series of three head fractures within 3 months. AB - A report is given of a series of three ceramic head fractures involving articulation with polyethylene cups. No sure cause for the marked increase in occurrence could be found, as the heads were not from the same manufacturing lot, nor was there evidence of a material defect or an error in the implantation technique. Head fractures in the combination ceramic-polyethylene are reported very rarely because of the very low statistical probability. For this reason the present authors are continuing to use ceramic heads, but wish, in the interests of "informed consent," to draw attention to the risk of head fractures. PMID- 8217457 TI - A clinical, radiological and biomechanical study of the TARA hip prosthesis. AB - We reviewed 60 patients with 72 TARA (total articular replacement arthroplasty) resurfacing hip prostheses. To analyse the behaviour of the femoral component a radiographic study was done and a two-dimensional finite element model was constructed. The stem of the femoral component plays a role in the load transfer mechanism. Stress shielding is seen in the proximal femur but depends on the interface conditions. When only the dome of the cup is assumed to be bonded to the bone, the stresses in the head increase dramatically and there is no more stress shielding. Five years after implantation radiographic signs of loosening of the femoral component were seen in 6.8% of the implants placed without notching in the femoral neck and in 28.6% of the components with notching (significant difference, P = 0.0005). Signs of loosening of the acetabular component were seen in 37.7% 5 years postoperatively. The cumulative survival rates of the femoral and acetabular components were 89.7% and 85.6% respectively 5 years after implantation. The overall clinical results are represented by an integration of the clinical results (Harris Hip Score System), the radiographic results and the survival analysis. This gave a success rate of only 72% 5 years after implantation. PMID- 8217458 TI - Results of conservative treatment of unilateral cervical spine dislocations. AB - Unilateral cervical dislocations are less common and have fewer accompanying neurological complications than bilateral dislocations. Being therefore rated as "less serious", these injuries are often treated non-operatively. A review of 292 patients presenting with acute spine injuries revealed 32 cases of unilateral dislocation (11%). Analysis of their management showed that non-operative treatment was mostly unsatisfactory. Twenty-four of the 32 (75%) eventually required surgical correction. Surgery led to good results in all of these cases. We recommend surgery as a method of choice for patients with unilateral cervical dislocations. PMID- 8217459 TI - Clodronate increases the calcium content in fracture callus. An experimental study in rats. AB - Eighty-eight rats underwent intramedullary pin fixation and fracture of both tibiae. Half of the animals were given clodronate 50 mg/kg s.c. weekly. Clodronate treatment did not affect the growth of fibrocartilage or the endochondral and membranous new bone formation. The regaining of tensile load capacity of fractured bone remained unaffected by the drug. Calluses were remodeled to lamellar bone in both groups. However, although the total area invaded by mineralized tissue in callus remained unaffected by the drug, the areas of hematopoietic bone marrow tissue within mineralized callus were observed to be markedly smaller in clodronate-treated animals than in controls. The calluses in the clodronate group were significantly heavier and contained more calcium at 2 months after fracture than those in the controls. PMID- 8217460 TI - Callus formation after re-injury to experimental bone defect. AB - Osteochondrogenic callus formation after delayed re-injury at different time intervals was evaluated. Twenty young rats were operated, and a standard bone defect reaching the medulla was sawn into the left hind leg. The rats were divided into two groups and the defect was re-created after 4 or 12 days. The rats were killed 7 or 14 days after the second operation. The developing new bone was revealed with a triple fluorochrome labelling system. The areas of bone and cartilage were measured histomorphometrically. The results suggested that an external factor, re-trauma, could increase both external and internal primary osteogenic callus formation. The optimum time to potentiate bone formation in the defects was found to be earlier than identified in previous fracture studies. After a 4-day delay the external callus was significantly larger than after the 12-day delay. Cartilage formation was not enhanced despite the sudden increase in osteogenic callus formation. PMID- 8217461 TI - Osteosynthesis for longstanding nonunion of the lateral humeral condyle. AB - Six patients with symptomatic longstanding nonunion of the lateral humeral condyle were treated by internal fixation with iliac bone graft. The indication for surgery was pain and weakness in the elbow. Follow-up ranged from 18 months to 4 years, with an average of 28 months. Bony union was achieved in all cases. Stability and strength of the elbow were restored in all cases, but postoperative elbow motion was decreased in three patients, with an average loss of 6.7 degrees of the motion present before surgery. All patients were painfree in the elbow upon strenuous activities and satisfied with the outcome of the procedure. PMID- 8217462 TI - Effect of upper tibial osteotomy on fibula movement and ankle joint motion. AB - Several techniques of upper tibial osteotomy in the treatment of unicompartmental osteoarthritis of the knee have been described. Osteotomy of the fibula is normally also carried out, or alternatively, dissection of the capsule of the proximal tibiofibular joint. There is concern, however, that this latter procedure may have an adverse effect on the mobility of the ankle joint and on fibula rotation. To investigate these suspected interactions we performed experimental studies in 14 cadaver legs. The vertical, lateral and rotational movements of the fibula were measured with the ankle in neutral (0 degrees) and maximal ankle dorsiflexion before and after performing an interligamental upper tibial osteotomy of a standardised valgus wedge. Maximal ankle dorsiflexion before the osteotomy produced external rotation of the fibula in most specimens, whereas after osteotomy this movement caused mainly internal rotation. In the neutral position of the ankle, upper tibial osteotomy lead to external rotation of the fibula. The upward movement of the fibula head after osteotomy was 0.64 cm on average. There was no measurable vertical motion of the fibula during ankle dorsiflexion either before nor after upper tibial osteotomy. Ankle dorsiflexion improved minimally after osteotomy. In conclusion, this study shows that upper tibial osteotomy with dissection of the capsule of the proximal tibiofibular joint has no adverse effect on movement of the fibula or of the ankle joint. In addition, unlike fibular osteotomy, this technique also has the advantage that the risk of common peroneal nerve injury is minimal. PMID- 8217463 TI - Non-traumatic dislocation of tibialis posterior tendon in a child. A case report. AB - A case of spontaneous dislocation of the tibialis posterior tendon in a 12-year old boy is presented. Closed reduction under general anaesthesia was performed, and after immobilisation for 6 weeks in a plaster cast no recurrence was observed. This case illustrates an unusual case of habitual dislocation of the tibialis posterior tendon treated by conservative means. PMID- 8217464 TI - Three-stage excision of recurrent cervical chondrosarcoma. A case report. AB - A case of cervical chondrosarcoma that recurred after incomplete excision is presented. The mass was removed in three stages and the involved vertebrae were fused. Excision of the huge mass with only minor complications was only possible by staging the procedure. Due to the location of the lesion, only marginal excision could be performed and the patient was given adjuvant radiotherapy. No signs of recurrence have been detected at 1-year follow-up and surgical measures to improve the function of the neurologically involved extremity are being undertaken. PMID- 8217465 TI - Clinical value of combined contrast and radionuclide arthrography in suspected loosening of hip prostheses. AB - Combined contrast and radionuclide arthrography was performed in 71 cemented, non cemented and hybrid hip arthroplasties for diagnosis of component loosening. In 31 cases, either one or two prosthesis components were clearly loose upon clinical and radiological diagnosis, with subsequent intraoperative confirmation. The other 40 cases had doubtful component loosening, with discrepancy between clinical and radiological findings, and were investigated for clarification. Contrast and radionuclide arthrograms were compared with sequential plain radiographs and their ability to indicate component loosening was evaluated. The combined contrast and radionuclide arthrograms proved in 90.9% of the cases whether a loose component existed as confirmed by intraoperative findings. They had a high sensitivity, specificity and predictive accuracy for both the acetabular and the femoral component. Sensitivity and predictive accuracy were remarkably precise in comparison to those of plain radiographs on the acetabular side. In nearly all patients with contradictory clinical and radiological findings, conclusive diagnosis was possible on the basis of the contrast and radionuclide arthrograms. Coinciding positive results in both contrast and radionuclide arthrograms were verified in each operated case. The combination of contrast and radionuclide arthrography is an useful method to diagnose doubtful loosening of hip arthroplasty components, especially in addition to routine sequential plain radiographs. PMID- 8217466 TI - Chondromyxoid fibroma of the sternum. Case report. AB - We report the second case of chondromyxoid fibroma (CMF) of the sternum, documented in the literature. In this case, only histology of the biopsy was useful in diagnosing CMF before definitive surgery. A wide subtotal resection of the sternum and reconstruction with a Gore-Tex soft tissue patch was performed. PMID- 8217467 TI - Carbohydrate histochemistry of skin glands in the Turkish Angora goat. AB - The skin glands of the general body surface of the Turkish Angora goat were studied by means of selected carbohydrate histochemical methods, in particular several PO-lectin procedures. Both gland types exhibited intensive secretion production, irrespective of season and body region. The different histochemical staining procedures demonstrated that glycoconjugates, especially neutral glycoproteins are present in the secretory cells and secretion products of the apocrine glands. The peroxidase (PO)-lectin-procedures indicated the following saccharide residues: alpha-D-mannose, N-acetyl-beta-D-glucosamine, alpha-D glucose, N-acetyl-D-galactosamine, beta-D-galactose, alpha-D-galactose, and alpha fucose, including small amounts of N-acetylneuraminic acid and N glycolylneuraminic acid. Relatively large amounts of glycoconjugates, probably also glycolipids, were found in the peripheral cells and the sebum of the sebaceous glands, exhibiting the following saccharide residues: N-acetyl-D galactosamine, alpha-fucose, N-acetylneuraminic acid and N-glycolylneuraminic acid. The results obtained are discussed as related to findings from corresponding studies in other mammalian species. The secretory substances present obviously create a clearly alkaline pH milieu within the fleece of the Angora goat. Such conditions are also known to exist, for example, in the Merino sheep fleece. PMID- 8217468 TI - The impact of target size on the level of the energy metabolism of spinal motoneurons. An enzyme histochemical and morphological study. AB - We investigated the relationship between the enzyme histochemical properties of motoneurons and the size of their peripheral target. The study was carried out on zebrafish (Brachydanio rerio) of 18 to 53 mm body length. Motoneurons of the white, fast glycolytic muscle (WMN) and of the slower red and intermediate oxidative muscle (RIMN) were investigated. We determined the average soma size of the WMNs and the RMNs and the following histochemical characteristics: Glucose 6 phosphate dehydrogenase (G6PDH), a marker for reductive biosynthesis; Phosphofructokinase (PFK), a marker for glycolytic activity; Succinate dehydrogenase (SDH) enzyme of the citric acid cycle and NADH tetrazolium reductase (NADH-TR) a marker for oxidative activity. The product of enzyme activity and the soma volume was denoted the enzyme capacity of a soma. As a measure for the average target of the motoneurons, we took the number of endplate regions within the white and the red-intermediate muscle. The age dependent increase in G6PDH capacity of motoneuron somata correlates significantly with the increase in the number of endplate regions. On the basis of changes in the soma size, enzyme capacity and target size, we estimate that in 18 mm fish about 45% and in 53 mm fish about 60% of the oxidative capacity is used to maintain connections with the target. This holds for WMNs as well as for RIMNs. Similar calculations, on basis of data known from the literature, indicate that in motoneurons of the cat, less than 10% of the oxidative capacity is used for connections with the target. The PFK capacity increased unproportionally with age in WMNs but not in RIMNs. This indicates that the energy metabolism in WMNs of large fish tends to be anaerobic glycolytic. The study shows that enzyme histochemical characteristics of motoneurons should be interpreted in a morphological context, regarding motoneuron soma size and target size. PMID- 8217469 TI - Development of the pelvic plexus in human embryos and fetuses and its relationship with the pelvic viscera. AB - Development of the pelvic plexus is studied in 15 human embryos and 2 fetuses ranging in size from 4 to 132 mm. C.R. length. A tridimensional reconstruction of the entire pelvic block was made in two specimens (30 and 132 mm. C.R. length) 80 X. The first ganglionic elements appear in Carnegie's stage 16, but the real definition of what in the final anatomy of the plexus is described as the hypogastric ganglion (Lee-Frankenhauser) is formed in stage 18. Complete development of the plexus occurs in stage 23. Other relevant facts are: the appearance in stage 18 of the pelvic splanchnic nerves, which are formed from S2, S3 and S4, the involvement of S1 and S5 were not observed in any case. In all specimens studied, a close proximity was seen between the pelvic plexus and genitourinary organs. Starting in stage 18, the terminal ureter consistently crosses the posterosuperior part of the pelvic plexus. PMID- 8217470 TI - Mast cell association with collagen fibres in human breast stroma. AB - Whirl-like structures consisting of strands and bundles of collagen fibres with a central space are described in human breast stroma. Association between these structures and connective tissue mast cells is demonstrated. Mast cells in these whirls, in contrast to those in loose connective tissue, showed signs of secretory activity. On ultramicroscopy some showed electron-dense bud-like structures at the edge of the cell, and between this and adjacent collagen bundles. In the absence of cytoplasmic cover association was demonstrated between the surface of a mast cell granule and a band of collagen fibres in the stroma. In vitro production of collagen fibres was reported in 1952 on the addition of heparin powder to soluble collagen. The mechanism of that reaction was not further defined. Neither, as yet, is that underlying the present findings. The products of mast cell granules would appear to be common to both. It is suggested that these findings may represent an alternative pathway for collagen deposition in vivo, as in vitro. PMID- 8217471 TI - Predictors of sexual behavior change among men requesting their HIV-1 antibody status: the Chicago MACS/CCS cohort of homosexual/bisexual men, 1985-1986. AB - It has been proposed that human immunodeficiency virus (HIV) antibody testing and counseling are effective means of altering sexual behavior among individuals at risk of HIV infection and transmission. However, the evidence supporting this hypothesis is inconclusive. This study examines the factors associated with sexual behavior change among a group of participants in the Chicago MACS/Coping and Change Study (CMACS/CCS) who requested their HIV antibody status when they were first given the opportunity, between 1985 and 1986. A set of demographic and psychosocial predictors were tested in association with 4 possible outcome patterns of sexual behavior change during the time of antibody status disclosure. For comparative purposes, a randomly selected sample of men who did not request disclosure of their HIV antibody status was analyzed. The results revealed that, among the 177 individuals who requested disclosure, the group experiencing an adverse sexual behavior change (i.e., from low risk before disclosure to high risk after disclosure) reported, before disclosure, the highest level of mental distress and denial-fatalism coping strategies and had the lowest levels of social support compared with other groups being analyzed. The psychosocial predictor most strongly associated with adverse sexual behavior change appears to be the use of denial-fatalism coping. Such an association was not found among the nondisclosed comparison group. These results suggest that a subgroup of at-risk, well-educated, white men, with overall high knowledge of HIV transmission, may not benefit from current HIV counseling and testing. Such men at risk for adverse behavioral outcomes might be identified in advance of HIV-1 antibody testing by their psychosocial profile, and thus appropriate counseling resources could be targeted to them. PMID- 8217472 TI - Racial differences in sexual behaviors related to AIDS in a nineteen-city sample of street-recruited drug injectors. NADR Consortium. AB - Questionnaire data from almost 12,000 street-recruited drug injectors in 19 cities were analyzed to determine racial differences that may affect transmission of the human immunodeficiency virus (HIV). Self-reported sexual behaviors of drug injectors differ by city-type. White male drug injectors reported less unprotected vaginal sex than black or Latino males in multicultural- black/white/Mexican-origin and biracial cities. Black drug users of both sexes were less likely than white or Latino drug users to report unprotected and sex in multicultural--black/white/Mexican-origin and multicultural--black/white/Puerto Rican cities. The reported percentage of sex acts in which a condom was used was similar for black, white, and Puerto Rican men, and for black and white women, in all city types, but Puerto Rican women reported more condom use than black women. Mexican-origin drug injectors of each gender were least likely to report using condoms in multicultural--black/white/Mexican-origin cities. Black drug injectors are particularly likely to report having sex partners who do not inject drugs, as are Puerto Rican men and as are whites in multicultural--black/white/Mexican origin cities. High-risk sex without condoms is widely reported among all groups of drug injectors studied: Each racial/gender group in each city-type averaged 15 or more episodes of unprotected vaginal sex per month, and 10% of most subgroups report having anal sex within the past 6 months. At least 45% of subjects in each city-type reported sex with noninjectors of the opposite gender. Without continued and expanded intervention, these data are consistent with HIV spreading to drug injectors, their sexual partners, and their future children, in all racial/ethnic groups. PMID- 8217473 TI - No joking matter: formal and informal sources of information about AIDS in Zimbabwe. AB - One hundred and forty-two social work students in Harare, Zimbabwe, were questioned concerning their sources and memory of information concerning the human immunodeficiency virus (HIV) and AIDS. Newspapers were cited most frequently as the major source of information. Family and friends were not reported to be major sources of information. An analysis of the kinds of items most frequently recalled showed that articles concerning personal portrayals were the most powerful vehicles for AIDS information. Metaphors and similes for AIDS produced by the students mirrored those commonly reported elsewhere. Jokes were studied as indicators of informal opinions, and these showed negative views of American involvement in AIDS issues. PMID- 8217474 TI - Why don't young adults protect themselves against sexual transmission of HIV? Possible answers to a complex question. AB - Using theories of health behavior, this study aimed to advance the understanding of risk-taking regarding human immunodeficiency virus (HIV) infection among young adults by describing: (a) their representation (i.e., schema) about HIV infection, (b) their problems with use of condoms and comfort with safe-sex practices, and (c) situations associated with risky sexual behavior and reported reasons for risk-taking. Participants were 272 young adult college students whose average age was 19.3 years (SD = 2.4). They completed an extensive questionnaire developed for the study. The representation of HIV infection in this sample lacked the specific and detailed information necessary to guide sexual behavior. For example, participants were aware of the causes of sexual transmission of HIV, but many persons indicated uncertainty about the effectiveness of various preventive strategies (e.g., latex condoms, birth control devices). A number of specific problems with using condoms were identified or expected by participants. These included inadequate lubrication, poor fit, and breaks or leaks during intercourse. The majority of the sample (85.3%) reported at least one occurrence of unprotected sexual intercourse. For 60% of them, the stated reason for the risk-taking was that the intercourse was unplanned or spontaneous; 50% reported that they "just knew" the partner was safe and not infected with HIV. Implications for health education programs are discussed. PMID- 8217475 TI - HIV-related risk and antibody testing: an urban community survey. AB - The present study investigated patterns of human immunodeficiency virus (HIV) antibody testing in a diverse urban sample. Five hundred seventy-nine men and women (representing 88% cooperation and 67% response rates) were surveyed in Chicago's downtown at mass transit waiting areas. Participants completed measures of demographic information, sexual and HIV-risk behavior histories, information regarding HIV antibody testing status, and HIV/AIDS-related knowledge and perceptions. Results showed that only 36% of persons with histories of high-risk practices had been tested for HIV. Persons who had been tested, as compared to those not tested, were older in age and perceived themselves to be at greater risk. Results also showed a relationship between participants' knowledge of their own HIV serostatus and inquiring about their sexual partners' serostatus. As compared to persons not tested, those who had been tested were more likely to know their most recent sexual partner's HIV testing status. Results suggest that several factors found among gay men with regard to HIV testing may generalize to populations representing diverse HIV-related risk behavior patterns. PMID- 8217476 TI - Psychosocial factors associated with condom use among African-American drug abusers in treatment. AB - Although strategies for decreasing injection drug use have met with moderate success, efforts to decrease high-risk sexual behaviors have been less successful. Because condom use reduces HIV transmission, it is critically important to identify the attitudinal, emotional, and behavioral factors associated with using condoms. This study evaluated the relationship between condom use and various psychological and behavioral variables among heterosexual, African-American, cocaine-dependent men within the context of the AIDS Risk Reduction Model (ARRM). Subjects who used condoms (n = 52) reported significantly higher levels of self-efficacy, condom use skills, and sexual communication with partners than non-users (n = 84). However, the groups did not differ in perceived susceptibility, anxiety concerning HIV transmission, response efficacy, or knowledge regarding HIV. These findings suggest that future interventions focus on enhancing self-efficacy and condom use skills, as well as eroticizing condom use. PMID- 8217477 TI - HIV-illness, social support, sense of coherence, and psychosocial well-being in a sample of help-seeking adults. AB - This study tests a set of hypotheses that predict self-esteem and anxiety in adults infected with human immunodeficiency virus (HIV). The analysis is motivated by the following question: Is the level of perceived coherence, i.e., the extent to which individuals derive meaning and purpose in their lives despite their HIV-illness, related to their levels of self-esteem and anxiety? Data were obtained from one of three HIV care and referral centers in the Midsouth. The results demonstrate that clients who experienced a greater sense of derived meaning and purpose (perceived coherence) from their situations and those with more confidants (social support) reported higher self-esteem and lower anxiety than other HIV-infected adults seeking counseling and maintenance services. Implications are drawn for strategies to meet HIV-related mental health care needs. PMID- 8217478 TI - Continuing medical education for AIDS: an organizational response. AB - The Management of the Southern California Kaiser-Permanente Medical Group mandated a day-long program of continuing medical education on AIDS for all staff physicians at one facility. Presentations dealt with cognitive (transmission/diagnosis), skills (risk factors, history taking), and affective (discomfort/attitudes) domains. All physicians participated in 2 small-group workshops on sexual history taking and ethical issues. An evaluation compared primary care physicians' attitudes and practices before and after the program at the experimental site (Medical Center), a comparison site (written materials only), and a "no-treatment" facility. A sample of new patients (N = 2,689) seen by study physicians (N = 253) before and after the educational intervention were telephoned to determine if sexual history questions were asked by their physicians. There was a significant increase in the frequency of sexual history questions asked by internists at the experimental site. Over 95% of all patients were accepting of sexual history questions. This program has since been repeated at 11 medical centers involving over 3,500 Kaiser-Permanente physicians throughout Southern California. PMID- 8217479 TI - [Current views on the etiopathogenesis of type-I diabetes mellitus]. AB - In the last few years the improvement of our knowledge of the pathogenesis of type I diabetes mellitus has been possible mainly because of the development of studies of the role played by genetic factors and the better definition of lesion mechanisms. The availability of experimental models such as "non obese diabetic (NOD)" mice and "Bio-Breeding (BB)" rats, which develop a form of type I diabetes similar to that of humans, has provided many data regarding the relevance of T lymphocytes in the pathogenesis of the disease, and made it possible to anticipate the immunopathological steps leading to pre-insulitis, insulitis and, finally, to pancreatic beta-cell destruction. The analysis of sera of patients with type I diabetes has demonstrated the presence, also in the preclinical states, of several autoantibodies directed against specific autoantigenic structures of beta cells, which have come to be useful for early diagnosis and in the monitoring of the disease. However, hard evidence for a relevant role of these autoantibodies in the pathogenesis of the disease does not exist. At present, we can affirm that the expansion of autoreactive T lymphocytes specific for membrane antigens of beta cells is the most relevant immunological event for the induction and sustenance of insular lesions. Autoreactive T lymphocytes may be able to activate several effector systems of lesions through the production of multiple combinations of cytokines. The aetiology of the disease is certainly multifactorial and involves both genetic and environmental factors. With respect to the former, the most accurate studies have been performed on the HLA system. It has been clearly shown that type I diabetic patients more frequently display HLA DR3 and DR4 specificities. The results obtained by the application of molecular techniques have suggested considering as risk factors the occurrence of DQB1 0302 DQB1 0201 alleles, the presence of a neutral amino acid residue in position 57 of the DQ beta chain instead of aspartic acid, as well as an arginine residue in position 52 of the DQ alpha chain. With regard to acquired aetiological factors, the hypothesis that primary lesions of pancreatic islets could be due to some viral infections capable of triggering, through several undefined mechanisms, persistent and self-sustaining autoimmune reactions, has gained some credit. PMID- 8217480 TI - [Retrospective study of Mycobacterium avium complex infection in the acquired immunodeficiency syndrome]. AB - We discuss here our experience with Mycobacterium avium complex (MAC) infection in 446 HIV-positive patients. MAC was found in 13 cases (2.9%): 10 males, 3 females, age range 21-47 years. Infection was disseminated in 10 cases and limited to the lung in 3. CD4+ cells were, on average, 48 per microliters. At clinical onset, all patients suffered from fever and weight loss, 10 from anemia, and 5 from diarrhea. MAC was found in its disseminated form in cultures of blood (10 patients), stool (5 patients) and urine (1 patient). Broncho-alveolar lavage seemed to be the most specific diagnostic method for lung infection. Twelve patients were treated with a multi-drug regimen consisting of an association of 4 or 5 antibiotics, selected on the basis of antibiogram, from the following: clofazimine, rifabutin, ciprofloxacin, ethambutol, isoniazid, amikacin and piazofolin. Mean survival of patients was 91.7%, 83.4%, 71.8% and 58.4% at 4, 5, 6 and 7 months of treatment respectively. Although the mean survival of the treated group is similar to that of untreated patients, multi-drug therapy seems to improve quality of life inasmuch as it brings temperature to normal and enables weight gain. Dissemination was never observed after treatment in patients with pulmonary infection only. PMID- 8217481 TI - Anti-cardiolipin antibodies in HIV infection are true antiphospholipids not associated with antiphospholipid syndrome. AB - The aim of the present study was to evaluate the fine specificity of anticardiolipin (aCL) antibodies detectable in the sera of patients with HIV infection. aCL are generally associated with thrombotic events in autoimmune diseases. A solid phase ELISA which discriminates between aCL binding to phospholipids and aCL binding to phospholipid/beta 2-glycoprotein I (cofactor) complex was employed. Thirty-nine HIV and 20 aCL positive systemic lupus erythematosus (SLE) sera were examined. In HIV sera, reduced binding to phospholipid was seen if cofactor was added. On the contrary, in SLE-sera the cofactor improved aCL binding. No thrombotic events were recorded in HIV infected subjects presenting with aCL. Thus, aCL in HIV infection and in SLE appear to have different specificities. In HIV infection the true epitope of aCL is likely to be on the phospholipid component only, whereas in SLE aCL seem directed against the cofactor/CL complex. Considering the anticoagulant role of beta 2 glycoprotein I, this observation might account for the lack of thrombosis in HIV patients with "true" aCL. PMID- 8217482 TI - [Prospective evaluation of the captopril test in diagnosing renal artery stenosis in hypertensive patients]. AB - In order to verify the utility of the captopril test (CT) in diagnosing renal artery stenosis we performed a prospective study in 94 consecutive patients (40 females, 54 males, mean age 52.4 +/- 12.3 years) suspected of having renovascular hypertension and with a serum level of creatinine < 2 mg/dl. Antihypertensive drugs were withdrawn one week before the CT or, if this was considered unsafe, patients were treated with nifedipine or diltiazem (53 subjects; 56.4%). We used renal angiography and the Muller criteria to interpret the CT. Our results were as follows: sensitivity, 92%; specificity, 96%; positive predictive value, 88%; and negative predictive value, 97%. In our study a simplified criterion for positive CT-postcaptopril plasma renin activity > 10 ng/mL/h-provided a similar diagnostic value. We conclude that the captopril test is a useful screening test for the detection of renal artery stenosis in selected hypertensive patients and that it can also be reliably performed in patients who are taking calcium antagonists. PMID- 8217483 TI - [Diet therapy in preventing the progression of chronic renal insufficiency]. AB - The effect of a low protein diet (LPD) on the progression of chronic renal insufficiency (CRI) was investigated by reviewing the published studies. Only the trials of Rosman, Ihle and Locatelli fulfilled the main methodological criteria of being randomized, prospective and controlled. They involved 811 patients (671 evaluated: 338 on an LPD, 333 as controls) and had a mean follow-up of 29 months (range 18-48) for an estimated total of about 17,335 patient-months. The only trial whose results showed that LPD had a positive effect on the progression of chronic renal failure (CRF) was Ihle's study with the lowest weight (6.7%) and which involved the most severe CRF; effects limited to the patients with more advanced CRF were found in Roman's study, with an intermediate weight (41.8%); and little effect, if any, in Locatelli's trial accounting for 51.5% of patient months, with less severe CRI. In conclusion, analysis of published randomized, prospective and controlled trials offers little or no evidence for the hypothesis that an LPD has a greater clinically significant effect on early CRI progression than a controlled protein diet, although a very low protein diet seems to postpone the need for dialysis. PMID- 8217484 TI - Intestinal malabsorption and related clinical syndromes. AB - The term malabsorption is used to define the defective passage of the products of normal digestion through the intestinal mucosa. The clinical consequences and expression of this phenomenon are extremely variable. This paper discusses in detail those conditions which, due to frequency, clinical polymorphism and difficulty in diagnosis or in therapeutic control represent particularly current problems in the field of Internal Medicine. At the clinical level, physicians more and more frequently find a dissociation between malabsorption, intended as a chemical-physical phenomenon, enteropathy, intended as a morbid process characterized by evident morphological alterations of the small intestine, and malabsorption syndrome, intended as a combination of symptoms consequent to malabsorption. Diseases of the small intestine are thus more frequently accompanied by minor, transitory and extra-intestinal symptoms. This explains why many such diseases still remain underdiagnosed. Since the chief clinical problem involves diagnosis, intestinal absorption should always be appropriately assessed even if the symptoms do not at first sight appear to be connected with malabsorption. PMID- 8217485 TI - Antiplatelet therapy in the prevention of cardiovascular diseases. AB - Antiplatelet agents have been studied in a number of clinical trials to evaluate their efficacy in the prevention of ischemic cardiovascular events related to platelet-rich thrombi. Acetylsalicylic acid (ASA) is definitely effective in the hospital phase of acute myocardial infarction; it also prevents cardiovascular events but not anginal attacks in patients with unstable angina and reduces the rate of occlusion of coronary artery bypass grafts. ASA is often used in the post infarction period, even though anticoagulant therapy is probably more effective; it is also effective in patients with transient ischemic attacks in the brain. Ticlopidine is the treatment of choice in patients with major stroke and in those with peripheral vascular ischemia; it can also be considered a valid alternative to ASA in the management of transient ischemic attacks and unstable angina. There is at the moment little role for antiplatelet agents in the primary prevention of cardiovascular disease. PMID- 8217486 TI - The present and future of radiolabelled antibodies in oncology. PMID- 8217487 TI - Changes in CA125 release and surface expression caused by drugs in uterine cervix adenocarcinoma cells. AB - The effect of drugs on the release of CA125 antigen and the binding of anti-CA125 monoclonal antibody (MoAb) to malignant cells was evaluated in vitro. TMCC-1, uterine cervical adenocarcinoma cells, were exposed to dexamethasone (DEX), sodium n-butyrate (NaB), dibutyryl cyclic AMP (dbcAMP), retinoic acid (RA), calcitriol (VD3), and interferon-gamma (IFN-gamma). NaB, RA and VD3 increased CA125 release per cell and 125I-labeled anti-CA125 MoAb binding to the cells. DEX also increased the 125I-labeled anti-CA125 MoAb binding to the cells, and CA125 antigen release per cell was also slightly increased. IFN-gamma suppressed both CA125 release and 125I-labeled MoAb binding. A combination of DEX, VD3 and RA and increased the binding of MoAb to TMCC-1 cells, but the amount of bound MoAb was not significantly different from that obtained by single drug treatment. DbcAMP had no significant effect on enhancing MoAb binding. Drugs can increase the binding of anti-CA125 MoAb to malignant cells and they may be applied to increase the tumor uptake of radiolabeled MoAbs in vivo. PMID- 8217488 TI - Difference in regional hepatic blood flow in liver segments--non-invasive measurement of regional hepatic arterial and portal blood flow in human by positron emission tomography with H2(15)O. AB - Organ blood flow can be quantitatively measured by positron emission tomography (PET). As the liver has dual blood supplies, arterial and portal, regional hepatic blood flow had not been measured quantitatively. However, we succeeded in simultaneously measuring both regional hepatic arterial and portal blood flow by PET in non-stressed patients. Mean regional portal hepatic blood flow in patients with normal liver and cirrhotic liver was 57.5 and 36.7 ml/minutes/100 g, respectively. Mean regional arterial blood flow was 42.5 and 30.7 ml/minutes/100 g, respectively. A significant difference between regional portal hepatic blood flows in normal and cirrhotic patients was noted. Mean regional portal hepatic blood flow in the lateral, medial, anterior, and posterior segments of the liver was 29.8, 43.4, 50.0, and 40.9 ml/minutes/100 g, respectively. Mean regional arterial blood flow in each liver segment was 37.6, 30.0, 28.2, and 31.6 ml/minutes/100 g, respectively. A significant difference between regional portal hepatic blood flows in lateral and anterior segment was noted. The p value was less than 0.025 and the 95% confidence interval of the difference between means was from -20.2 to -2.7 ml/minutes/100 g by ANOVA. These results showed that regional hepatic blood flow is not the same in all the liver segments. PMID- 8217489 TI - Thallium-201 scintigraphy in the evaluation of thyroid nodules. A retrospective study of 246 cases. AB - There is controversy at present concerning the value of Tl-201 scintigraphy in the diagnosis of malignant thyroid nodules. The usefulness of Tl-201 scintigraphy in differentiating benign from malignant nodules was evaluated retrospectively. Tl-201 scintigraphy was performed in 101 patients with malignant thyroid nodules and in 145 with benign nodules. Early and late images were examined to compare Tl 201 uptake in nodules and normal thyroid tissue. The visual method resulted in 74% of sensitivity and 58% of specificity for the detection of malignant nodules including incidental cancers. Excluding incidental cancers, 87% sensitivity and 58% specificity were achieved. Small cancers, including incidental cancers less than 1.5 cm in diameter and small number of viable tumor cells in a large tumor also gave negative Tl-201 scintigraphic results. Forty-two percent of the benign lesions gave false positive Tl-201 scintigraphic results. It is concluded that Tl 201 scintigraphy is a sensitive and useful method to use in diagnosing malignant thyroid nodules, but is not a specific method even with late scan, for the detection of malignant thyroid nodules. PMID- 8217490 TI - The role of adrenocortical scintigraphy in the evaluation of unilateral incidentally discovered adrenal and juxtaadrenal masses. AB - We reviewed the findings of adrenocortical scintigraphy with 131I-6-beta iodomethyl-19-norcholesterol (NCL-6-131I) of 39 patients to clarify its role in the evaluation of unilateral adrenal or juxtaadrenal masses incidentally discovered by CT, ultrasonography or plain radiography. Twenty-seven benign adrenal masses showed various scintigraphic findings (hot nodule: 12 silent adenomas, warm nodule: one solid mass, normal appearance: one cyst and 2 solid masses, diffuse decrease: each one; solid mass, myelolipoma, ganglioneuroma and calcified adrenal and partial or complete defect: each one; solid mass, myelolipoma and ganglioneuroma and 2 cysts and 2 pheochromocytomas); while a partial or complete defect was shown in a nonfunctioning carcinoma and 3 metastases and a complete defect or inhomogeneous uptake without opposite adrenal visualization was shown in 2 patients with cortisol-producing carcinoma. Therefore a hot nodule and an inhomogeneous uptake or complete defect with nonvisualization of the opposite adrenal are specific to a benign tumor and a cortisol-producing carcinoma, respectively. The impaired tumor uptake of NCL-6 131I is a nonspecific finding. The scintigraphic findings of juxtaadrenal masses were normal in 4 and deviated adrenals in 2. Thus adrenocortical scintigraphy can identify silent adenomas and cortisol-producing carcinomas among the adrenal masses and may help to differentiate juxtaadrenal from adrenal masses. PMID- 8217491 TI - Evaluation of critically perfused area in acute ischemic stroke for therapeutic reperfusion: a clinical PET study. AB - To evaluate critically perfused areas in the acute ischemic brain, 9 patients were studied by positron emission tomography (PET) within 7-32 hours after the onset. The cerebral blood flow (CBF) and oxygen metabolic rate (CMRO2) were evaluated and compared with sequential change in CT findings. In all the regions developing subsequent necrosis on CT, CBF dropped below 17 ml/100 g/min. But in some of these lesions, CMRO2 remained above the minimum value for regions in which infarction did not develop, and the tissue density on CT obviously remained normal for several hours after PET scan. The mean CBF in these lesions (14.0 ml/100 g/min, range: 9.9-17.3 ml/100 g/min) was significantly higher than that in ischemic areas with low density on CT before or just after PET study (approximately 10 ml/100 g/min, range: 7.7-14.1 ml/100 g/min). These findings suggest that a part of the tissue with CBF between 10-17 ml/100 g/min is still viable at least 7 hours after the onset of ischemia, but becomes non-viable in a longer period of ischemia. These lesions should respond to effective treatment, including therapeutic reperfusion. PMID- 8217492 TI - High reactivity of [11C]CH3I with thiol group in the synthesis of C-11 labeled radiopharmaceuticals. AB - High reactivity of [11C]-methyl iodide ([11C]CH3I) with the thiol group was demonstrated with cysteamine and other compounds containing a thiol and another functional groups in each structure. The methylation of the thiol group in cysteamine with [11C]CH3I was very rapid at 0 degree C with no catalyst, and gave a high radiochemical yield and purity without any detectable by-product. Moreover, this reaction was not disturbed by the other functional groups, such as -NH2, -OH and -COOH in the same structure. This S-methylation reaction is very useful for producing a new radiopharmaceutical labeled with the short lived positron emitting nuclide C-11. PMID- 8217493 TI - Gallium-67 scintigraphy in an adult intussusception caused by malignant lymphoma. AB - A rare case of adult intussusception caused by malignant lymphoma (ML) of the cecum was reported. In spite of the cecum lesion, strong 67Ga accumulation was located in the right epigastrium. This finding was useful in suggesting the presence of intussusception due to ML. PMID- 8217494 TI - Demonstration of abnormal perfusion in the pons with high resolution SPECT and technetium-99m HMPAO in a patient with acoustic neuroma. AB - We detected a regional defect in the pons with ipsilateral cerebellar hypoperfusion in a patient with acoustic neuroma by brain SPECT with 99mTc HMPAO. A high spatial resolution SPECT system with three detectors equipped with fan beam collimators was employed. This is the first report of a defect in the brainstem being visualized by perfusion SPECT and this method could make it possible to clarify the cause of a remote effect on the cerebellar perfusion by injury to the brainstem. PMID- 8217495 TI - Differentiation of transiently ischemic from infarcted myocardium by thallium-201 exercises scintigram after active ergometer rehabilitation. AB - It has been frequently reported that while myocardial viability is neglected in conventional methods of diagnosis such as left ventriculography, ECG, and exercise thallium-201 myocardial scintigraphy (Ex-Tl), revascularization often results in improving left ventricular wall motility. In the present study, the authors contrived a method to accurately evaluate the viability of the myocardium by means of exercise rehabilitation, and tested the method in clinical cases. Among patients with myocardial infarction, we selected a patient with negative viability in the diseased area as determined by chronic ECG, left ventriculography (LVG), coronary angiography and Ex-Tl. This patient went through two weeks of active exercise rehabilitation gauged with an ergometer, and was then re-examined by Ex-Tl. After the evaluation, revascularization was performed for the patient who demonstrated viability of the infarcted myocardium in EX-Tl after rehabilitation, and significant improvement in contractility was shown in the chronic LVG. These findings indicate that our method of detecting potential viability of the infarcted myocardium is of clinical significance. PMID- 8217496 TI - Long-term follow-up studies on iodine-131 treatment of hyperthyroid Graves' disease based on the measurement of thyroid volume by ultrasonography. AB - In the present series of studies, the long-term (four year) effect of 80 Gy of 131I treatment was evaluated in patients with hyperthyroid Graves' disease whose thyroid volumes have been accurately estimated with a high resolution ultrasound scanner. One year after 131I treatment, 23.1% (3 out of 13 patients) remained hyperthyroid, 69.2% (9 out of 13) became euthyroid, and 7.7% (1 out of 13) were in a hypothyroid state. Since three patients in a hyperthyroid state one year after treatment were subsequently treated with either antithyroid drugs or additional 131I treatment, the remaining ten patients (9 euthyroid and 1 hypothyroid patients) have been followed up for three more years. Two patients developed a hypothyroid state three years after treatment and one patient four years after treatment. Overall, 60% (6 out of 10 patients) were in a euthyroid state and 40% (4 out of 10) in a hypothyroid state, four years after 80 Gy 131I treatment. There was no significant difference between eu- and hypothyroid groups in the sex ratio, age, radiation dose, therapeutic dose, thyroid gland volume, 24 hr 131I uptake, the effective half-life of 131I in the thyroid or the duration of hyperthyroidism. In our preliminary studies, the incidence of late hypothyroidism in our 131I treatment is similar to those previously reported. These suggest that uncertain factor(s), such as inhomogeneity of iodine distribution in the thyroid, unequal sensitivity of the thyroid cells to the radiation, and/or persistent destructive effects of the autoimmune process may influence the long-term effect of 131I treatment of Graves' disease. PMID- 8217497 TI - Brain tumor accumulation and plasma pharmacokinetic parameters of 2'-deoxy-5-18F fluorouridine. AB - Using positron emission tomography and radio-high performance liquid chromatography, the accumulation of 2'-deoxy-5-18F-fluorouridine in the brain tumors and plasma pharmacokinetic parameters were investigated in 20 patients. High accumulation of the tracer in high grade gliomas and meningiomas and very rapid degradation of the tracer in the plasma were found. Very large variations were observed in both tumor accumulation and pharmacokinetic data. The tumor accumulation, however, did not correlate with any of the plasma pharmacokinetic parameters: area under the plasma concentration-time curve, mean residence time, total body clearance and steady-state volume of distribution. The results suggest that the accumulation of the tracer reflects the metabolic activity of the brain tumor tissues and that the effect of the rapid metabolic change in the tracer in the plasma on the tumor accumulation may be minor. PMID- 8217498 TI - Neurovascular and molecular mechanisms in migraine headaches. AB - This chapter reviews the evidence that challenges traditional and unproven notions which perpetuate the singular importance of constriction and dilation to the genesis of migraine pain. New data in experimental laboratory models suggest that migraine headache may develop primarily from metabolic/neurophysiological events (as yet unidentified) within the cortical mantle, or from a disturbance in those regions of brain which closely approximate the distribution of trigeminovascular fibers innervating meningeal blood vessels. Accordingly, this chapter will review the consequences of trigeminovascular activation to pain and meningeal inflammation, and will summarize emerging molecular and pharmacological data suggesting that ergot alkaloids and sumatriptan alleviate pain primarily via activation of pre-junctional 5-HT1 heteroreceptors residing on primary afferent trigeminovascular fibers. PMID- 8217499 TI - Involvement of interleukin-1 and lipocortin-1 in ischaemic brain damage. AB - The cytokine interleukin-1 (IL-1) is synthesised within the brain and acts as a mediator of host defence responses to disease and injury. Several of these central actions of IL-1 are inhibited by an endogenous calcium and phospholipid binding protein, lipocortin-1. Synthesis of IL-1 and lipocortin-1 in the brain is markedly increased by neuronal damage, and inhibition of the actions of endogenous IL-1 by central injection of IL-1 receptor antagonist in the rat significantly inhibits ischaemic and excitotoxic brain damage. Lipocortin-1 appears to act as an endogenous neuroprotective agent that markedly attenuates ischaemic and excitotoxic damage. In contrast, inhibition of the actions of lipocortin-1 by injection of neutralising antiserum exacerbates both forms of neurodegeneration. The mechanisms underlying these effects of IL-1 and lipocortin 1 are largely unknown, but are probably independent of changes in body temperature. Actions of these molecules on corticotrophin releasing factor, arachidonic acid, excitatory amino acids, and nitric oxide, and the possible involvement of these factors in brain damage are discussed. PMID- 8217501 TI - [Research and pediatric surgery]. PMID- 8217500 TI - Functional neuroimaging with single photon emission computed tomography (SPECT). AB - Single photon emission computed tomography (SPECT) is a technique for producing regional maps of the in vivo distribution of radioactively labelled tracers without either the complexity or the cost of positron emission tomography (PET). Use of commercially available single photon emitting tracers such as 99mTc, 123I, or 201Th with longer half-lives than positron emitters eliminates the need for an on-site cyclotron and greatly simplifies the radiopharmacy requirements. In addition, the ability to produce images using gamma cameras which are routinely available in most nuclear medicine departments has considerably reduced the capital asset cost of imaging. SPECT is not an inexpensive procedure but it is much cheaper than PET. It is not possible to use the ideal biological labels of carbon, nitrogen, or oxygen with SPECT or to measure metabolic rates for oxygen or glucose. It is, however, now possible to image the distribution of cerebral blood flow with a reasonably well-validated technique, to investigate tumour viability, and to study an ever-increasing range of neurotransmitter receptor systems using SPECT. SPECT may have its technical limitations but it is the functional imaging technique which is likely to be available to most clinicians and, as experience with its application to a variety of pathological conditions grows, a much broader benefit from functional neuroimaging than could be produced by PET alone will result. The purpose of this review is not to compare SPECT with PET, but to give an overview of how SPECT works and what has been established in studies of various pathologies. In some cases, the clinical role of SPECT has already been established and in some it is emerging, but in other cases SPECT is a measurement tool for research purposes which is unlikely ever to be used routinely. PMID- 8217502 TI - [Outcome of conservative treatment of high-degree vesicoureteral reflux]. AB - We performed a retrospective study to evaluate the results of a nonsurgical approach of primary high grade vesicoureteral reflux (VUR). 241 patients (209 III and 32 IV) were reviewed during and average time of 9.4 years. 55% of them were under 6 months and 52% had bilateral reflux (50% III and 63% IV). During the observation period spontaneous resolution of reflux was observed in 126 (60%) with grade III at 5 years and 26% in patient with grade IV at 4 years. In both grades the duration of persistent reflux was analyzed using life-table method. When age at presentation was compared with duration of reflux there was a shorter time of reflux in those patients presenting from age 0 to 6 months. New renal scars developed in 5 patients during the period of observational therapy. We conclude that high grade VUR can resolve over a protracted interval. On basis of this analysis, we advocate the surgical correction in these patients after 5-year period to grade III and 2-year to grade IV. PMID- 8217503 TI - [Prognostic factors in congenital diaphragmatic hernia. Can they modify our therapeutic approach?]. AB - Mortality rate from congenital diaphragmatic hernia (CDH) is still high despite current therapeutic advances. For some time now we have been looking for prognostic parameters which be enable us to determine, in the prenatal and postnatal period, the patients who will die from their pulmonary hypoplasia in spite of treatment and those who will survive. The authors review 94 newborns with CDH diagnosed during the first 24 hours of life. The following prognostic parameters were studied: preoperative arterial gases, position of stomach, right or left sided hernia, liver in thorax and presence of postoperative pneumothorax. All these factors were related to mortality. The arterial gases were the most sensitive factor. Eighty per cent of patients with poor gasometric prognosis died. Thoracic stomach is also a poor prognostic parameter with a 76.7% mortality rate, however we think this does not justify prenatal surgical measures. The remaining parameters were not significant with regard to mortality. PMID- 8217504 TI - [Anorectal manometry in the newborn]. AB - Anorectal manometry was performed in 32 newborn. There were 18 preterm and 14 fullterm infants, mean ages 6.1 and 7.1 days respectively. The rectoanal inhibitory reflex (RIR) was positive in 31 of the newborn, and the relaxation waves produced by rectal distention were recorded along the anal canal and were directly correlated to intensity of the stimulus. In the remaining patient RIR was negative, due to Hirschsprung's disease, confirmed at surgery. The length of the anal canal was 10.3 +/- 2 mm. in preterm newborn infants and 14.7 +/- 2.9 mm, in fullterm (p < 0.0001). These findings suggests that presence of RIR is independent of the weight, gestational age and birth age of the infant, and that anal canal length is correlated with the weight of the infant. We conclude that anorectal manometry, in the neonatal period, is a simple, reliable and safe method to test anorectal functionality, including the study of Hirschsprung's disease. PMID- 8217505 TI - [Duodenogastric reflux: values in normal children and in children with gastroesophageal reflux]. AB - Duodenogastric reflux (DGR) is a natural event, occurring occasionally and whose pathological significance is not well known. The accuracy of 24-hour gastric pH metry for the DGR diagnosis has been tested in adults but not in children. For this purpose we measured the area under curve (AUC) at pH 4, 6 and 7 and the percentage of total time above pH 4 (%pH4), 6 (%pH6) and 7 (%pH7), excluding the 2-hours post-prandial period in 88 children suspected of having gastroesophageal reflux (GER). Forty were considered normal whereas 40 had acid GER and 8 with GER. In the control group %pH4 was 9.68 +/- 14.1, %pH6 3.4 +/- 8.7 and %pH7 1.0 +/- 2.4. The values for AUC were 101 +/- 112.8, 16.5 +/- 22.3 and 3.3 +/- 6.1 pH unit/min, respectively. Comparable results were found in the acid GER group. On the other hand alkaline refluxes had higher figures for all parameters: %pH4 22.1 +/- 13.9, %pH6 12 +/- 13 y %pH7 7 +/- 12, AUC at pH 4,406.5 +/- 410, 136.1 +/- 194 at pH6 and 48.2 +/- 85.1 at pH7 (p < 0.05). Because of the large dispersion of values in the control group we selected the 95 percentile, as the upper limit of normal values instead of the mean +/- SD. Therefore the upper limit were 27 for %pH4, 9 for %pH6 and 3.8 for %pH7. The AUC, 316, 64 and 16 pH/min, respectively. These results prove that DGR in children is a very common event and confirm that DGR definitely contributes to alkaline GER. PMID- 8217506 TI - [Study of intestinal motility in the child with acute appendicitis using phonoenterography]. AB - Our experience in using the phonoenterographic procedure in measuring the sounds produced by the intestinal motility in 75 patients is reported: 30 underwent surgery, won acute appendicitis, 20 appendicular peritonitis and 25 underwent surgery without abdominal pathology. We performed in all patients a temporary record of 3 minutes of duration, one spectrogram and one sonogram before the surgery and after surgery in the following 6, 12 and 24 hours. We obtained the number of sounds recorded by our informatic program, and also its intensity measure in dB and frequency in Hz. The procedure we have used can distinguished the characteristics of the intestinal sound of each patient and allow to show a qualitative and quantitative activity, different in the three group of patients. The number of sounds is bigger in the patients with non digestive abdominal pathology and smaller in patients with peritonitis. In general, the lesser number of sounds the lesser intensity and a more grave tones. PMID- 8217507 TI - [Surgical technique in reduced hepatic transplantation in children]. AB - The lack of availability of pediatric donors for liver transplant has resulted in a high mortality rate among children awaiting transplantation, especially in patients weighing less than 10 kg. Knowledge of techniques of liver reduction allows liver transplantation in low-weight children with an adult liver graft, although with increased risk. The authors studied 70 pediatric liver transplants, 14.3% of whom received a reduced-size organ. Maximal difference between donor and recipient weight was 7.7. Segments II, III and IV (right hepatectomy) were transplanted in eight cases while segments II and III were transplanted in two cases. Transfusional requirements during the 48 hour postoperative period were not significantly different between patients with reduced-size liver and patients who received the full-size organ. There was not morbi-mortality secondary to surgical technique in reduced liver transplant group of patients. PMID- 8217508 TI - [Urologic complications in renal transplantation in children]. AB - Our results with 105 pediatric renal transplantations, are reviewed. The identified complications were: 4 ureterovesical stenoses, 1 pyeloureteral stenosis, 1 vesical rupture, 1 vesicoureteral reflux on native ureters and 1 acute urinary obstruction. These incidences were scattered among 5 patients of whom 3 had 2 complications each. All were surgically corrected and 4 of the kidneys are well-functioning at present. We analyze the factors possibly involved and suggest that donor and recipient related parameters might not be determinant, save for those patients afflicted with lower urinary tract anomalies, and that ureteral catheters may prevent urinary extravasation or fistulae. PMID- 8217509 TI - [Metabolic balance in newborns receiving parenteral nutrition]. AB - It has been realized a study about energy and nitrogen balances in 23 patients with total parenteral nutrition in order to know how they get weight increase and nitrogen retention. The parameters analysed were nitrogen retention, nitrogen retention/100 g. of weight increase, efficacy in use of nitrogen, metabolized energy and metabolized energy expressed in percentage of intake energy. Positive correlation between intake energy and urinary eliminated energy (p < 0.05) as soon as between intake nitrogen and urinary eliminated nitrogen emphasize among the results. We have verified too that the percentage of metabolized energy over intake energy is upper in operated newborn than in other affected by necrotizing enterocolitis. PMID- 8217510 TI - [Fetal nutrition in intestinal atresia. Studies on the chick embryo]. AB - This paper examines the effects of experimental prenatal intestinal obstruction on the growth and blood composition of chick embryos. Intestinal atresia (IA) was produced by bipolar bowel electrocoagulation in fertile eggs on the 14th day of incubation. The chicks sacrificed on the 19th day were measured, weighed and blood-sampled. Twenty-three control, 10 sham-operated and 11 IA chicks were studied. Animals with IA were severely undernourished by weight (43.4 +/- 4.7 vs 70.3 +/- 7.6% of egg weight, p < 0.001) and length (15.3 +/- 1.1 vs 18.1 +/- 9 mm. tibial length, p < 0.001) in comparison with sham-operated ones. Their haematocrit was slightly lower, and total protein increased. Pre-albumin was absent in their sera and albumin, alpha and beta globulins were significantly decreased whereas gamma-globulin was greatly increased. Sodium, potassium chloride, urea and glucose remained within normal limits. The lack of placenta in the avian embryo precludes any supply of nutrients by this route and the ingestion of amniotic fluid, which is protein-rich after the 13th day of incubation, when the opening of the sero-amniotic connection allows albumen to be mixed with it, becomes the main source of nutrients until hatching. Obstruction of the main incoming avenue by IA induces severe malnutrition in this model which relies on this route to a greater extent than the human foetus. In spite of the obvious biological differences between the avian embryo and the human foetus, the present evidence supports the hypothesis that prenatal interruption of the amniotic fluid transit contributes to foetal undergrowth in IA. PMID- 8217511 TI - [Neoformation of intestinal mucosa on dura mater patches. Application in the surgical treatment of short bowel syndrome. Experimental study in rats]. AB - The creation of intestinal neomucosa on grafts or materials implanted in the intestinal wall is one of the therapeutic procedures that has been tested in the short bowel syndrome. This paper presents the results obtained after intestinal implanting lyophilised dural patches in an experimental model of massive intestinal resection in rats. Data were contrasted with those of a control group subjected to massive resection without patches. The findings reveal: 1) high mortality related to the surgical technique; 2) slight improvement in the ponderal curve; 3) slowing down of intestinal transit; 4) neomucosa on the patch, with histological characteristic similar to normal. We conclude that although the creation of neomucosa on dural patches is feasible and conditions a slight improvement in the animal's nutritive status, application of the procedure is not practical in treatment for the short bowel syndrome due to the high mortality rate. PMID- 8217512 TI - [Therapeutic approach in a fetus with posterior urethral valves]. AB - A pregnant woman was diagnosed with fetal uropathy at 18 weeks gestation. A thorough examination revealed bilateral hydronephrosis, megacystis with bladder neck and posterior urethral dilatation, normohydramnios, normal echocardiography and normal male karyotype. From the 20th week on she developed a progressive oligohydramnios, and the left kidney became hyperechogenic. Fetal urine analysis at week 21 showed hypotonic urine in both renal pelvises, and a beta 2 microglobulin of 8.5 mg/l. on the right side and 18 mg/l. on the left one, suggesting some degree of function on the right kidney. A vesico-amniotic shunt was placed at week 22, which was ineffective, and another shunt was placed two weeks later. Twenty-four hours later the bladder size decreased, but amniotic fluid did not increase and a great amount of ascitis developed, which was attributed to catheter migration. On week 25, the abdomen was decompressed through a peritoneal-amniotic shunt. Ascitis decreased thereafter, but oligohydramnios remained unchanged. The patient died 20 hours after a cesarean section was performed at the 31st week. The necropsy diagnoses were: posterior urethral valves, bilateral renal dysplasia and pulmonary hypoplasia. This case illustrates the difficulty in establishing a prognosis based on the prenatal data available at present. PMID- 8217513 TI - [Treatment of radial club hand with double articulated external fixators]. AB - Congenital absence of the radius is a rare malformation, characterized by radial deviation of the hand to more than 90 degrees. Early treatment with plaster cast use to be enough to correct radial deviation, making easier surgical correction on several years later. We report a case of a newborn with radial club hand absence of the thumb of the right hand, bilateral hydronephrosis and bilateral cryptorchidism. Was treated with a new procedure, permitting wrist centralization, coupled with osteotomy and callostasis of the ulnar diaphysis using external fixation. We obtained an important success with this serial lengthening of the ulna. PMID- 8217514 TI - A predictive model for the combined effect of pH, sodium chloride and storage temperature on the growth of Brochothrix thermosphacta. AB - Growth of Brochothrix thermosphacta was observed under ranges of pH (5.6-6.8), NaCl (0.5-8.0% w/v) and incubation temperature (1-30 degrees C). In order to compare different approaches, two models were used to fit growth curves to viable count data, and to calculate parameters from those fitted curves. Growth responses as a function of pH, NaCl and temperature were described with a quadratic function which was then used to predict growth within the limits where growth was observed. The predictions of the model show good agreement with published observations from other laboratories. PMID- 8217515 TI - Antagonistic activity of two strains of lactic acid bacteria against Listeria monocytogenes and Yersinia enterocolitica in a model fish product at 5 degrees C. AB - The antagonistic activity of lactic acid bacteria against one strain of Listeria monocytogenes, Scott A and one strain of Yersinia enterocolitica serotype O:3 was studied by using either a strain of a Leuconostoc spp. or a Lactobacillus plantarum strain. Each of the two potential pathogenic, psychrotrophic bacteria were inoculated with either of the two lactic acid bacteria in sterile shrimp extracts containing citric acid (pH 5.8 and 6.0) and in some experiments also 3% (w/v) NaCl. The samples were incubated at 5 degrees C. Antagonistic effect was obtained with both lactic acid bacteria against both pathogenic organisms, with the effect depending on inoculation levels of the pathogenic organism, the lactic acid bacteria strain and media composition. PMID- 8217516 TI - Heat resistance of fungi from soil. AB - The survival of fungi from soil samples has been investigated after exposure to temperatures of 60, 70, 80 and 90 degrees C in Sabouraud agar. The least resistant fungi surviving 60 degrees C for 60 min were the Aspergillus (A.) niger group, Chaetomium spp, Penicillium spp, and Scytalidium lignicola. None of these survived 70 degrees C for 10 min. The next group surviving 70 degrees C for 60 min included the A. glaucus group, Byssochlamys nivea, Dichotomomyces cejpii, Gelasinospora spp, Rhizoctonium spp, and Talaromyces flavus; they did not survive 80 degrees C for 10 min. At 80 degrees C for 60 min, survival was seen for Aspergillus fumigatus, Aspergillus nidulans, Eupenicillium baarnense and Ulocladium spp; they did not survive 10 min at 90 degrees C. Acremonium sclerotigenum, Aspergillus ochraceus, Botryotrichum piluliferum, Byssochlamys fulva, Gilmaniella humicola, Neosartorya fischeri, Nodulisporium sp. and Talaromyces avellaneus survived heat treatment at 90 degrees C for 10 min and longer time with the two last being the most resistant. The phenomen of activation of dormant spores by thermal shock was not apparent. PMID- 8217517 TI - Effects of temperature, aw and pH on the growth of Bacillus cells and spores: a response surface methodology study. AB - Effects of water activity (aw), pH and storage temperature on the growth of spores and vegetative cells of Bacillus spp. isolated from bakery products were studied in a model system and the growth was monitored spectrophotometrically in microtitre plates. Experiments, performed following a Central Composite Rotatable Design and aimed at development of response surfaces, resulted in two polynomials based mainly on first order coefficients. For both cells and spores, temperature, aw and pH acted additively and without any synergistic effect. This was also confirmed by isoresponse plots for the combinations temperature-aw, temperature pH and pH-aw. Applications of the models to predict the shelf life of the actual food product are discussed. PMID- 8217518 TI - Lipolytic activity and degradation of rapeseed oil and rapeseed by spoilage fungi. AB - Aspergillus, Eurotium and Penicillium spp. from rapeseed were able to grow and produce lipases over a range of water activities (aw) at both 15 and 25 degrees C on tributyrin agar. The ability to produce lipases was not directly related to growth rate. The clearing zone: growth rate ratios gave lipase indices which varied markedly between test fungi and with aw. The fungi with the highest indices were Aspergillus candidus and Aspergillus versicolor and Penicillium expansum and Penicillium hordei. The Aspergillus spp. generally grew faster on a 1% crude rapeseed oil at 25 degrees C and 0.995 and 0.95 aw than on the tributyrin agar. P. hordei degraded the rapeseed oil more rapidly than Eurotium amstelodami or Penicillium aurantiogriseum, with optimum activity at 0.98 aw. E. amstelodami was the least effective at degrading the rapeseed oil under all aw conditions. The lipase indices were compared with the ability of the test fungi to degrade irradiated rapeseed. Dry matter loss over 4-week periods were greater at 25 than 15 degrees C, regardless of aw. At 15 degrees C, Penicillium spp. caused significantly greater dry matter losses than Aspergillus spp. A. niger degraded rapeseed faster than other Aspergillus spp. tested at 0.98 aw, but at 0.95 and 0.90 aw there was little difference between species. PMID- 8217519 TI - Incidence of Listeria species in raw and pasteurized milk produced in Sao Paulo, Brazil. AB - The present study evaluated the incidence of Listeria spp. in raw and pasteurized milk from a Brazilian dairy plant. Ten samples of each type of milk (raw types B and C and pasteurized types B and C) were collected monthly from October 1989 to September 1990 (except in December), comprising 440 samples (110 samples of each type of milk). The recovery of Listeria spp. was carried out using LPM (lithium chloride phenylethanol moxalactam) and MOX (modified Oxford) agars, after a two step enrichment procedure in Listeria enrichment broth (LEB) and Fraser broth. Overall, 12.7% of raw milk samples, 0.9% of pasteurized milk samples and 6.8% of total of milk samples were positive for Listeria spp., while 9.5% of raw milk samples, none of the pasteurized milk samples and 4.8% of total milk samples, were positive for Listeria monocytogenes. Raw milk also contained L. innocua (9.5%), L. welshimeri (0.9%) and L. grayi (0.4%). Pasteurized milk contained only L. innocua (0.9%). PMID- 8217520 TI - An acceleration of age-related increases in levels of the beta-subunit of nerve growth factor in selected tissues from senescence-accelerated mice (SAM-P/8). AB - An investigation was made of age-related changes in levels of the beta-subunit of nerve growth factor (beta-NGF) in selected tissues and of testosterone in serum in senescence-accelerated mice (SAM-P/8) and in the control mice (senesence resistant mice; SAM-R/1). The concentrations of testosterone in serum were higher in SAM-P/8 than in SAM-R/1 at ages 2 and 4 mo. The level of beta-NGF in the thymus from SAM-R/1 increased with age, resulting in a statistically significant difference in its level between mice at ages 2 and 12 mo. By contrast, there was a transient increase in SAM-P/8 at around age 4 mo with a subsequent decrease. Consequently, significant differences were apparent in levels of beta-NGF between the two types of mouse at ages 2 and 4 mo. Similar results were obtained in the adrenal gland and testis. Compared to SAM-R/1 at age 2 mo, the average concentrations of beta-NGF in the hypophysis were higher in SAM-R/1 at ages 4 and 8 mo and in SAM-P/8 at all ages. In other tissues tested, no remarkable differences were detected. Our present results indicate that, in SAM-P/8, the elevation in levels of beta-NGF in the thymus, adrenal gland, testis, and hypophysis occurs in the early period of life compared to the control mice. Possible dysfunction of the disorder of hypophysis is discussed. PMID- 8217521 TI - ARPP-39, a membrane-associated substrate for cyclic AMP-dependent protein kinase present in neostriatal neurons. AB - This study describes a cyclic AMP-regulated phosphoprotein that displays a distinct cellular and regional distribution in rat brain. The protein is found only in neostriatal regions, where it is enriched in nerve cells and not in afferent or efferent axons or in glial cells. On subcellular fractionation, it appears tightly associated with particulate components, possibly the synaptic plasma membrane fraction. The protein may therefore be specifically enriched in dendrites and/or somata of neostriatal neurons. Following phosphorylation in vitro with [gamma-32P]ATP and cyclic AMP-dependent protein kinase, the protein contains phosphoseryl residues on multiple thermolytic peptides. The specific cellular and subcellular localization we have observed suggests that this protein, termed ARPP-39 (cyclic AMP-regulated phosphoprotein, M(r) = 39,000) may be important in receptor-regulated, cyclic AMP-mediated functions in distinct neostriatal neurons. PMID- 8217522 TI - Regional and developmental variations of GFAP and actin mRNA levels in the CNS of jimpy and shiverer mutant mice. AB - Gliosis is a common reaction to brain damage. Glial fibrillary acidic protein (GFAP) is a classical astrocytic marker. We have undertaken to measure the level of GFAP-mRNA as an index of gliosis in the brain of jimpy (jp) and shiverer (shi) murine mutants, in which hypomyelination is either severe or moderate, respectively. This study was conducted in five different CNS regions and at different ages. In young jp mutant, the amount of GFAP-mRNA was either normal or lower than in control animals; but after 3 wk of age, the level of GFAP transcript increased dramatically in all regions examined. A parallel increase in actin-mRNA was also observed, mostly in the diencephalon and to a lesser extent in cortex and spinal cord, but not in the cerebellum and brainstem. In the shi mutant, variations in the amount of GFAP-mRNA were less important than in the jp with two exceptions: In brainstem of 3-wk-old animals, a 2.5-fold increase was observed, and in all the regions but the spinal cord of 12-d-old shi, the levels of GFAP-transcript were 2-5 times lower than in controls. In this mutant, the levels of actin message were usually close to normal, or slightly lower than in controls. PMID- 8217523 TI - Induction of peptidylglycine alpha-hydroxylating monooxygenase activity by nerve growth factor in PC12 cells. AB - Pheochromocytoma PC12 cells grown in the presence of nerve growth factor (NGF) undergo marked neuronal differentiation. During this process gene expression is altered, resulting in the activation of genes specific for neuronal properties, including the gene encoding neuropeptide Y (NPY). Here we sought to determine whether NGF also induces the activity of peptidylglycine alpha-hydroxylating monooxygenase (PHM) (EC1.4.17.3). PHM catalyzes the rate limiting step in the formation of alpha-amidated NPY from its glycine extended precursor, a posttranslational modification essential for biologic activity. PC12 cells were grown with or without NGF and assayed for PHM activity under optimal conditions. Whole cell extracts, medium and soluble and membrane bound fractions were assayed; total cellular PHM activity was found to be primarily membrane bound (fivefold greater than in soluble) and very little activity was released into the medium. Compared to control cells, PHM activity was increased significantly by NGF by 24 h but not before 4 h exposure. Through kinetic analysis, it was determined that the NGF-induction of PHM was a result of an increase in Vmax with no change in Km. It was found that the glucocorticoid, dexamethasone (DEX), decreased basal PHM activity and prevented its induction by NGF. Cotreatment with DEX for up to 7 d, however, did not dramatically alter the pronounced changes in cell morphology that occurred in response to NGF. These findings indicate that NGF and glucocorticoids exert reciprocal control over the activity of PHM in PC12 cells. As such, the process of differentiation in PC12 cells is a model for studying the mechanisms that coordinate the expression and activity of peptide processing enzymes with the regulation of their substrates and products. PMID- 8217524 TI - Pattern recognition of 31P magnetic resonance spectroscopy tumour spectra obtained in vivo. AB - Pattern recognition has been applied to the analysis of in vivo 31P NMR spectra. Using four different classes of tumour and three types of normal tissue, cluster analysis and artificial neural networks were successful in separating and classifying the majority of samples analysed. Although the phosphomonoester and P(i) regions appeared to be the most important spectral features, data representing the entire 31P spectrum were required for best separation of the tumour and tissue classes. PMID- 8217525 TI - Quantitative analysis of 1H NMR detected proteins in the rat cerebral cortex in vivo and in vitro. AB - Spectral editing experiments were used to quantify CH3 groups from macromolecular species in the chemical shift region from 1.2 to 1.4 ppm of rat cerebrum in vivo. Two peaks centred at 1.22 and 1.40 ppm were revealed when irradiation was positioned at 4.35 or 4.30 ppm. These peaks had lower saturation factors (1 vs. 1.72 +/- 0.10) than N-acetyl aspartate (NAA) and shorter T2 [60 +/- 5.8 (1.22 ppm) and 51 +/- 2.2 (1.40 ppm) vs. 123 +/- 12 (NAA) ms]. The concentrations of the peaks at 1.22 and 1.40 ppm were calculated to be 0.65 +/- 0.09 and 1.37 +/- 0.18 mmol of CH3 equivalents/kg brain. Acid extract from cerebral cortices contained macromolecular peaks at the same chemical shifts with approximately the same area ratios to NAA as in vivo. These data show that the macromolecular peaks in the brain at TE > 100 ms arise predominantly from proteins which are acid soluble. The assignment of macromolecular signals in the cerebral spectrum to a given polypeptide (thymosin beta 4 and histone H1) is discussed in the light of protein analyses of brain acid extracts. PMID- 8217526 TI - In vivo assessment of mitochondrial functionality in human gastrocnemius muscle by 31P MRS. The role of pH in the evaluation of phosphocreatine and inorganic phosphate recoveries from exercise. AB - In this study we compared the kinetics of phosphocreatine (PCr) and P(i) recovery, and their dependency on cytosolic pH in 38 normal individuals. Spectra were acquired during rest, work and recovery. A time resolution of 10 s was used to obtain detailed information. The kinetics of PCr and P(i) recovery almost overlapped when the lowest value of cytosolic pH reached during recovery (termed the minimum pH) was < 6.95, while they were completely dissociated when the minimum pH was > 6.95. This result is interpreted as indirect in vivo evidence of the kinetic control exerted by ADP on mitochondrial oxidation. Our results represent a rationale for new experimental conditions to be used in clinical routine studies of pathologies due to primary or secondary mitochondrial malfunction. PMID- 8217527 TI - The influence of medium formulation on phosphomonoester and UDP-hexose levels in cultured human colon tumor cells as observed by 31P NMR spectroscopy. AB - High-resolution 31P NMR spectroscopy at 11.7 T was used to examine the influence of medium formulation (medium and serum type, and concentrations of glucose and inositol) on the cellular phosphate metabolism of CX-1 cells, a human colon cancer cell line derived from HT-29 cells. Striking differences in the 31P spectra of harvested CX-1 cells were observed. The largest variation was seen in the phosphocholine and UDP-hexose levels (up to seven-fold changes), with smaller differences in the levels of other phosphate metabolites. The major UDP-hexose species were found to be UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine (ca 2:1 ratio), which have been proposed in the literature to be markers of cell differentiation status. Medium-induced alterations in metabolite levels were much greater than the normal variations seen in CX-1 control samples grown under identical conditions. They even exceeded the characteristic differences observed between different human tumor cell lines grown under one set of culture conditions. The remarkable sensitivity of CX-1 cellular phosphate metabolism to the culture environment has implications for the comparison of in vitro vs in vivo spectra, and for the interpretation of effects due to growth and therapy. PMID- 8217529 TI - Neoadjuvant therapy for gastrointestinal cancers. AB - Neoadjuvant (primary) chemotherapy is an attractive concept for upper GI tract malignancies and to a lesser extent rectal cancer to increase local control, as well as to destroy micrometastasis. Endoscopic ultrasonography for esophageal, gastric, and rectal cancers is a new tool that may allow identification of appropriate high-risk patients for such investigational approaches. In esophageal cancer, radiation therapy alone has probably been supplanted by combined concurrent systemic chemotherapy and radiation. Phase III trials of chemotherapy prior to operation are currently underway. Phase II trials of neoadjuvant chemotherapy are underway in gastric cancer. In rectal cancer, while the use of postoperative adjuvant chemotherapy plus radiation is firmly established, more recent data suggest that there may be less toxicity with preoperative treatment, and in selected patients may result in increased potentially curative resection rates. PMID- 8217528 TI - Extracellular volume and transsarcolemmal proton movement during ischemia and reperfusion: a 31P NMR spectroscopic study of the isovolumic rat heart. AB - We have measured, directly and simultaneously, changes in extracellular volume and intra- and extracellular pH during ischemia in the isolated rat heart using 31P NMR spectroscopy. Hearts were perfused with buffer containing 15 mM sodium phenylphosphonate at pH 7.4. Wash in and wash out experiments showed that phenylphosphonate entered only the extracellular (interstitial, vascular and chamber) space of the heart and had no adverse effects on myocardial energetics, contractile function or coronary flow rate. Hearts were subjected to 28 min of total, global ischemia, during which the phenylphosphonate resonance area in the 31P NMR spectra decreased by 83%, indicating that extracellular fluid had moved rapidly from the heart to the bath surrounding the heart, partly as a result of vascular collapse. A separate, morphological study confirmed that 95% of the vasculature had collapsed by 28 min ischemia. Intra- and extracellular pH were determined from the chemical shifts of the P(i) and the phenylphosphonate resonances, respectively. In the pre-ischemic rat heart, intracellular pH was 7.15 +/- 0.03 and extracellular pH was 7.39 +/- 0.03. By 4 min of ischemia, intra and extracellular pH were the same and decreased concomitantly throughout the remainder of ischemia to final values of 6.09 +/- 0.19 and 6.16 +/- 0.23, respectively. On reperfusion, the extracellular volume and pH returned to pre ischemic levels within 1 min, but restoration of intracellular pH took > 2.5 min. Thus, a large volume of extracellular fluid moves out of the rat heart to the surrounding bath and the intra- and extracellular pH become the same during total, global ischemia. PMID- 8217530 TI - Suggestions to prevent and manage chemotherapy extravasation. PMID- 8217531 TI - Hyponatremia in the cancer patient. AB - Hyponatremia is a common metabolic complication in cancer patients. It can be caused by the primary tumor itself, metastasis, by diagnostic or therapeutic interventions, or by a secondary complication. A clear understanding of water and sodium homeostasis is required for evaluation. The initial diagnostic step is to define a hypoosmolar state. The history and physical examination should be tailored to determine the volume status of the patient--volume depleted, euvolemic, or edematous. In general, hyponatremia associated with volume depletion is treated with saline, while fluid restriction is the primary therapy in patients with normal or increased extracellular fluid volume. In symptomatic patients, the duration of the hyponatremia and its causes should be determined. Both overzealous and inadequate treatment put the patient at risk of serious neurologic sequelae. PMID- 8217532 TI - Oncology nursing in the small community hospital. AB - Coordinating the nursing component of a community hospital's cancer program requires a clear definition of the facility's mission as it relates to cancer care and the scope of cancer nursing within the facility. Program managers need to assess the hospital's strengths and weaknesses, as well as local, regional, and national trends that impact on the hospital's ability to implement a cancer care program that is fiscally realistic and salient to its targeted population. The major advantages community hospitals have over large medical centers are convenience and ability to control the hospitalization experience. Nurses play a key role in creating a positive experience for patients and families in a variety of cancer care services, including prevention and early detection, community outreach and education, standard cancer therapy, ambulatory care, and other post acute services. PMID- 8217533 TI - Chemotherapy for malignant gliomas. AB - An increase in the incidence of malignant gliomas has been noted over the last two decades. Chemotherapy, either adjuvant or at recurrence, has extended the survival of patients with malignant gliomas. Oligodendrogliomas and anaplastic astrocytomas represent the most chemosensitive tumors, while glioblastomas have been relatively resistant to any treatment modality. The most active agents include carmustine, procarbazine, and eflornithine, and combinations such as lomustine, procarbazine and vincristine, or thioguanine, dibromodulcitol, procarbazine, lomustine, fluorouracil and hydroxyurea. Although chemotherapy has demonstrated some efficacy against malignant glioma, new therapeutic strategies are needed for this devastating disease. PMID- 8217534 TI - Munchausen's-by-proxy syndrome. PMID- 8217535 TI - Cardiovascular collapse after high dose methylprednisolone. PMID- 8217536 TI - Polycythemia: a review article and case report of erythrocytosis secondary to Wilms' tumor. AB - We describe a child with Wilms' tumor whose only finding at presentation was polycythemia. A review of the mechanism of erythropoiesis regulation as well as the differential diagnosis, work-up, and management of polycythemia in children is presented. Our report emphasizes the need for a thorough evaluation of children who present with polycythemia. PMID- 8217537 TI - Children with cancer talk about their own death with their families. AB - In this study we looked at children dying from progressive malignant diseases and their families, to see whether they discussed the child's impending death together. We also looked at what factors might influence this. We questioned staff in the oncology department about their attitude to an open approach in talking about death and their views of how often it occurred. Analysis of 31 children over 3 years old and their families showed that the approach of death was mutually acknowledged by six families (19%); seven (23%) children were felt to know but chose not to discuss death; in two (6%) families, discussion with the child was blocked; nine (29%) children died unaware, and in seven (23%) families, what the children felt was unknown. Staff members (22) all advocated an open, honest approach in talking to children about their death but varied widely and overestimated how often they believed discussion of the child's impending death occurred (range, 10%-80%; median, 45%). PMID- 8217538 TI - Central venous catheter with subcutaneous injection port (Port-A-Cath): 8 years clinical follow up with children. AB - Long-term intermittent venous access was established in 77 children by means of a central venous catheter (CVC) with a subcutaneous injection port (Port-A-Cath; PAC). Seventy of these children were included in this follow-up study. Sixty three were treated for different malignant diseases, five for cystic fibrosis, one for severe hemophilia and one for central nervous system disease with seizures as the main problem. As of April, 1992, PACs had been in place for 3/12 to 8 3/12 years (cumulative 175 5/12 years) with 2,206 entries into the system. The PACs were used for blood sampling and administration of chemotherapy, antibiotics, fluids, total parenteral nutrition (TPN) and blood products. Portal infection was observed in four patients of which two patients had their PAC removed. Catheter dislocation was observed in two and catheter breakage in one. Portal occlusion, extravasation, thrombosis leading to removal of the PAC or other technical or psychological complications were not observed. The children continued normal activities, and the easy venous access decreased emotional stress during treatment. Local doctors were trained to use PACs, through which they administered maintenance chemotherapy. We conclude that long-time use of PACs in children is safe and has many advantages compared to traditional CVCs in use. Strict indications, meticulous implantation techniques and adequate handling are, however, mandatory. PMID- 8217539 TI - Munchausen syndrome presenting as hemophilia: a convenient and economical "steal" of disease and treatment. AB - Munchausen's syndrome and Munchausen's syndrome by proxy (MSBP) can cause many conditions, including bleeding problems, seizures, failure to thrive and others. We report here an unusual case in which a mother presented to the hospital for her hemophiliac son's failure to thrive, subsequently for her own self-inflected mutilating wounds, and finally for self-induced simulation of her son's hemophiliac bleeding and arthritic complications. PMID- 8217540 TI - Unexplained menorrhagia and hematuria: a case report of Munchausen's syndrome by proxy. AB - Unexplained menorrhagia and hematuria occurred in a 13-year-old female with a mild inherited platelet disorder who had never experienced prior bleeding as a result of this disorder. An intensive search revealed that this patient was receiving coumadin that was given by the mother. In addition, the mother drew large volumes of blood from the patient under the pretense of following a physician's orders. The mother also falsified the laboratory data to erase from her daughter's file a laboratory result documenting warfarin in the blood. PMID- 8217541 TI - Cardiorespiratory decompensation following methylprednisolone administration. AB - A 2-year-old white female receiving multidrug chemotherapy for treatment of a primitive neuroectodermal tumor developed acute hypotension, bradycardia, and shock following administration of ondansetron and high-dose methylprednisolone. The subsequent clinical course is described, and cardiovascular reactions to ondansetron and methylprednisolone are reviewed. While the etiology of this severe reaction is uncertain, it is possible that it represents an idiosyncratic reaction to the rapid administration of high-dose adrenal corticosteroids. Patients receiving high-dose corticosteroid therapy should be closely monitored, and slow rates of infusion are recommended. PMID- 8217542 TI - Desferrioxamine and urinary zinc excretion in beta-thalassemia major. AB - This study has been undertaken to find out whether urinary zinc excretion, which is already increased in patients with thalassemia, is further increased by usual and high doses of desferrioxamine (DF). A total of 11 beta-thalassemia major patients were included. DF infusions have been performed with doses, either 50 mg/kg or 150 mg/kg. Nine age and sex matched normal children were taken as the control group. The mean basal-Zn excretion of the patients was significantly higher than the mean Zn excretion observed in controls. No significant difference is observed between the mean Zn excretion obtained on different doses of DF. However, they are both significantly higher than the mean basal-Zn levels of the controls. PMID- 8217543 TI - Diamond-Blackfan anemia associated with Treacher-Collins syndrome. AB - We describe a 2-year-old girl with a rare combination of congenital red cell aplasia or Diamond-Blackfan anemia (DBA) and Treacher-Collins syndrome (TCS). The anemia is only marginally responsive to high-dose corticosteroid, and the child is transfusion dependent. There is no one in the family affected with either DBA or TCS. A hypothesis is advanced that the simultaneous occurrence of the dysmorphism and erythroid agenesis in this case may have been the consequences of an insult to the fetus at the critical stage of development of maxillomandibular structure and the stage of primitive erythroid cell migration from the yolk sac to the fetal liver and bone marrow. PMID- 8217544 TI - Long-term cerebral effects of CNS chemotherapy in children with acute lymphoblastic leukemia. AB - Fifteen 7-16-year-old patients, treated in 1981-1984 for acute lymphoblastic leukemia (ALL) in first complete remission, were studied. As a central nervous system prophylaxis, all the children were treated with repeated methotrexate (MTX) instillations, but none were irradiated. The study protocol included magnetic resonance (MR) and a battery of neuropsychological tests. Small, punctate white-matter lesions were found by MR in eight children, probably minor vascular lesions. All the children were within normal intelligence range with a mean total WISC-R IQ of 109. Minor neuropsychologic problems were found in two patients, while one child showed a more extensive specific learning disorder in school. PMID- 8217545 TI - Congenital microangiopathic haemolytic anemia: a variant of thrombotic thrombocytopenic purpura? AB - We describe a child with recurrent microangiopathic haemolytic anemia (MAHA) and thrombocytopenia (TCP) who presented on the first day of life. Remission was maintained only by regular infusions of fresh frozen plasma (FFP). This case shows similarities with others described in the literature as examples of thrombotic thrombocytopenic purpura (TTP), although the absence of renal or neurological involvement distinguishes this disorder from classical TTP. PMID- 8217546 TI - Primary ocular recurrence of leukemia following bone marrow transplant. AB - A patient with acute lymphoblastic leukemia (ALL) who had undergone an allogeneic bone marrow transplant that included high-dose chemotherapy and total body radiation without eye shielding, sustained an isolated relapse of her disease in the iris. A review of ocular leukemic disease is discussed. PMID- 8217547 TI - Effect of nutritional status on the incidence of infection in childhood cancer. AB - In 52 children with cancer, the effect of nutritional status on infection rate was studied. Thirty-two children had solid tumors and 20 had leukemia. Their treatment courses were arbitrarily divided into 3-month periods. Where treatment lasted for 9 months or more, the initial Nutritional Status score was correlated with infection rate during the subsequent 3-month period. Among the leukemic patients, a statistically significant inverse correlation (P < 0.05) was found between nutritional status and ensuing infection rate. No such correlation was found in children with solid tumors. Based on these findings, we recommend nutritional support to children with leukemia during chemotherapy to attempt to reduce the infection rate. PMID- 8217548 TI - Hemoglobinopathies in the district of Antalya, Turkey. AB - A screening program was conducted to ascertain the incidence of hemoglobinopathies in the district of Antalya, Turkey. The survey sample was selected from the household registration forms of health centers by systematic random sampling. Heparinized blood samples were collected from 1,616 subjects from 884 families. The prevalence of beta thalassemia traits with increased Hb A2 was 10.2%. This is higher than that found in previous studies performed in Antalya. The prevalence of abnormal hemoglobins (Hbs) was found to be 0.8%. Four subjects had Hb AS; five had Hb D-Los Angeles (B 121 [GH4] Glu-Gln); one had Hb Ube-2 (68 [E1] Ans-Asp), one had Hb P-Nilotic (fusion between B 22 and) and two had Hb D-like variants. PMID- 8217549 TI - Recombinant interferon alfa-2b therapy in children with immune thrombocytopenic purpura. PMID- 8217550 TI - Central nervous system disease in childhood ALL. PMID- 8217551 TI - Long term effects of malnutrition during lactation on GALT. AB - In this report we present data that help to define the impact of malnutrition during the suckling period on the gut associated lymphoid tissues (GALT). Fifty day old rats malnourished during lactation presented a diminished percentage of s alpha +B cells and IgA level in the intestinal fluid. Also, a decrease in the CD4+ and CD8+ T cell subsets was found. At 120 days of age the percentage of s alpha +B cells and IgA level in the intestinal fluid was similar to the control. However, the percentage of T cells remained altered. When three doses of chorea toxin were administered orally since day 28, the IgA anti CT antibodies were diminished in the intestinal fluid, while the immunization schedule started after seven days of refeeding (28 days of age). This impairment of the immune response remained even after a CT booster was given to animals 113 days old. This diminishing in the CD4+ T cells may be the major cause of the nonresponsiveness described herewith. PMID- 8217552 TI - Changes in ocular mast cell numbers and histamine distribution during experimental autoimmune uveitis. AB - Choroidal mast cells have been implicated in experimental autoimmune uveitis (EAU), an ocular inflammatory disease induced by S-antigen. Our data confirm that choroidal mast cell numbers decrease with clinical onset of S-antigen-induced EAU in Lewis rats, and establish that the decrease is statistically significant. In addition, we find that the numbers of limbal mast cells also decrease during S antigen-induced EAU, and that this decrease occurs earlier in the course of the disease than that observed for choroidal mast cells. Activation and degranulation of mast cells, as evidenced by decreases in mast cell number, result in the synthesis and/or release of large quantities of mast cell mediators, such as histamine. Histamine levels in EAU were found to change significantly, decreasing in the anterior portion of the eye and increasing in the choroid and retina, in concert with changes in mast cell number over the course of EAU. Mast cell mediators may actively contribute to the pathogenesis of EAU through direct enhancement of the inflammation, by stimulation of other elements of the immune system, and/or through facilitation of the blood-retinal barrier breakdown that occurs in EAU. Overall, these results add to the evidence for a mast cell role in EAU, and, in addition, show that the mast cell involvement in EAU includes the mast cells of the limbus. PMID- 8217553 TI - The effect of immunization route on rat serum and tear antibody responses to Chlamydia trachomatis. AB - The effect of immunization route on the kinetics of serum and tear antibody responses to Chlamydia trachomatis was studied in a rat model. Rats received Chlamydia trachomatis serovar C/TW elementary bodies for two immunization cycles by ocular topical (OT) application or subconjunctival (SC) injection and in a second experiment for three immunization cycles by either OT application, gastrointestinal intubation (GI), or intraperitoneal injection (IP). Serum IgG and tear IgA antibodies to whole elementary bodies were measured sequentially following the secondary (2 degrees) and tertiary (3 degrees) immunization cycles. Serum IgG levels were minimal in the OT immunized group following 2 degrees and 3 degrees immunization. Serum IgG levels for the SC, GI, and IP immunized groups rose steadily following 2 degrees immunization reaching maximal levels between day (d)24 and d31. Levels of serum IgG antibodies were highest in the GI group following 3 degrees immunization. Tear IgA antibody responses were greatest in rats immunized by the OT route, the 2 degrees IgA response peaked by d9 and declined by d24. The 3 degrees OT tear IgA response peaked by d13 and was greater than the 2 degrees response. Tear IgA antibody levels in SC and GI immunized rats appeared by d3 following 2 degrees immunization but remained at low levels and were not noted until d20 in the GI group following 3 degrees immunization. Tear IgA antibody responses were not detectable in IP animals following 2 degrees or 3 degrees immunization. This study documents the immunogenicity of Chlamydia trachomatis serovar C/TW in the rat and shows that the OT route is most effective in eliciting IgA antibody responses in tears. PMID- 8217554 TI - The development and structure of mouse nasal-associated lymphoid tissue: an immuno- and enzyme-histochemical study. AB - This study deals with the structure and development of Nasal-Associated Lymphoid Tissue (NALT) in the mouse. NALT is present in the nasal cavity on both sides at the entrance of the pharyngeal duct. The lymphocytes are organized in B- and T cell areas covered by an epithelium in which M-cells are present. Immuno- and enzyme-histochemistry showed that NALT is already present at birth. Before birth, accumulations of Ia-positive dendritic cells and a few B lymphocytes were the first signs of the formation of NALT. These cell accumulations occurred just under the epithelium in the nasal floor. At birth, NALT could be distinguished as an accumulation of mainly B lymphocytes and Ia positive dendritic cells in a network of reticulum cells. The covering simple epithelium showed crypt-like invaginations. B- and T-cell areas appeared at seven days after birth. High endothelial venules (HEV) were observed from day 7 onward; from day 14 they could be stained with the HEV-specific monoclonal antibody MECA-325. Ia-positive dendritic cells increased in number during ontogeny. They occurred both in NALT and between the covering epithelial cells. Also, some epithelial cells expressed the Ia-antigen. The number of acid phosphatase positive macrophages increased steadily during ontogeny. The cells were mainly observed in the connective tissue surrounding NALT and just under the epithelium. They displayed antigenic determinants characteristic of macrophages (Moma-1, Moma-2). The structure and development of NALT are compared with those of other parts of the mucosa associated lymphoid tissue. PMID- 8217556 TI - Molecular biology of the skin introduction: approaches and principles. AB - This issue of Seminars in Dermatology describes our current understanding of the molecular nature of skin diseases. Some would say it is hubris to even contemplate this charge considering the rapid progress in molecular genetics. We implore the gods protecting the nucleotides to look kindly on our efforts. This introductory article discussed some general methodological considerations and techniques and provides a glossary of common terms used in molecular biology, useful for understanding this issue of Seminars in Dermatology. This article is aimed at neophytes to enhance their ability to enter the magical realm of the gene. The articles in this issue describe diseases with a defined defect at the DNA level or diseases in which there is a rapid closing in on the basic defect. PMID- 8217555 TI - Skn antigens: identification of a 95-kilodalton protein in mouse neural tissue. AB - Skn alloantigens represent a tissue-specific histoincompatibility system based on their expression in epidermal cells and absence in hematopoietic tissue. Radiation chimeras produced by lethally irradiating C57BL/6 mice and reconstituting them with (C57BL/6xA/J)F1 spleen cells reject skin from A/J (A) or (B6xA)F1 donors. The studies reported here were designed to determine the expression of the Skn 2.1 alloantigen on neural tissue given the common ectodermal origin of epidermal and neuronal cells. Using a monoclonal antibody specific for the Skn 2.1 alloantigen, a protein of 95 kilodaltons was identified in brain cells of A mice and, by immunohistochemical staining, Skn 2.1 was found in neurons in the brain. Although the antigen was detected in the cerebral cortex, cerebellum, and hippocampus of the brain, the staining of cells within these regions was not uniform. Because there is a restricted pattern of Skn 2.1 expression, limited to cells of ectodermal lineage, it is hypothesized that Skn may play a role in the differentiation of ectodermally-derived tissues. PMID- 8217557 TI - Molecular genetics of oculocutaneous albinism. AB - Oculocutaneous albinism (OCA) is a group of autosomal recessive disorders characterized by deficient synthesis of melanin pigment. Type I (tyrosinase deficient) OCA results from deficient enzymatic activity of tyrosinase, which catalyzes at least three steps in the melanin biosynthetic pathway. Type II (tyrosinase-positive) OCA results from abnormalities of the "P" polypeptide. Recent application of molecular genetic techniques to the study of these disorders has led to extraordinary advances in knowledge of their molecular pathogenesis, paving the way to improved diagnosis, carrier detection, and even treatment. PMID- 8217559 TI - Sjogren-Larsson syndrome. AB - Sjogren-Larsson syndrome (SLS) is an autosomal recessive disorder characterized by the presence of congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia. The ichthyosis is generalized in distribution, and histological features of the skin include hyperkeratosis, papillomatosis, acanthosis, and a mildly thickened granular layer. Electron microscopy shows lamellar membranous inclusions in the granular and cornified cells. SLS patients have impaired fatty alcohol oxidation caused by deficient activity of fatty aldehyde dehydrogenase, a component of the fatty alcohol:NAD+ oxidoreductase complex. This enzymatic defect provides a reliable means for diagnosing SLS patients and unaffected SLS carriers. Prenatal diagnosis of SLS can be accomplished by enzymatic studies of amniocytes and cultured chorionic villi cells, or by histological examination of a fetal skin biopsy. Although still unproven, fatty alcohol accumulation in patients is thought to be responsible for the cutaneous symptoms. PMID- 8217558 TI - Dystrophic forms of epidermolysis bullosa. AB - Recent advances in the molecular genetics of the various forms of epidermolysis bullosa have disclosed the underlying genetic mutations in several different genes. In the dystrophic forms of EB, several lines of evidence indicate that type VII collagen gene is involved. First, the anchoring fibrils that consist of type VII collagen are altered, or they can be complete absent. Secondly, genetic linkage analyses using informative intragenic RFLPs in the type VII collagen gene and flanking polymorphic markers on the short arm of chromosome 3 have established linkage in families with the dystrophic forms of EB. Finally, discrete mutations in the type VII collagen gene have recently been disclosed in patients with the recessive dystrophic form of EB. These advances now provide the means for early prenatal diagnosis from chorionic villus biopsies during the first trimester of gestation, and will allow diagnosis by blastomere analysis before implantation in the future. Furthermore, understanding the precise mutations in the dystrophic forms of EB sets the stage for gene therapy to reverse the clinical phenotype in affected individuals. PMID- 8217560 TI - Marfan syndrome: genetic basis and clinical manifestations. AB - Marfan syndrome is a systemic heritable disorder of connective tissue. The manifestations of the disorder are primarily from the musculoskeletal, cardiovascular, and ocular systems. Marfan syndrome is caused by mutations in the fibrillin gene located on chromosome 15. PMID- 8217561 TI - The Ehlers-Danlos syndromes. AB - The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of inherited connective tissue disorders characterized clinically by skin fragility, skin hyperextensibility, joint hypermobility, and excessive bruising. At least 10 different subtypes of EDS have been classified based on genetic, biochemical, and clinical characteristics. Recent advances in the molecular analysis of EDS have identified defects responsible for EDS IV (mutations in the type III collagen gene), EDS VI (homozygous and compound heterozygous mutations in the lysyl hydroxylase gene), EDS VIIA and VIIB (mutations in the type I collagen genes), EDS VIIC (deficiency of procollagen N-proteinase), and EDS IX (decreased lysyl oxidase activity). Very little is known about the genetic or biochemical defects responsible for the other EDS subtypes, but with the application of the tools of molecular biology, analysis of these defects is now within reach. PMID- 8217562 TI - Hypohidrotic (anhidrotic) ectodermal dysplasia: molecular genetic research and its clinical applications. AB - X-linked hypohidrotic (anhidrotic) ectodermal dysplasia (EDA) results in abnormal morphogenesis of the teeth, hair, and eccrine sweat glands. The disorder is inherited as an X-linked recessive trait with significant morbidity and mortality in affected males, but with little to no clinical expression in many carrier females. Therefore, despite much effort, carrier detection based on clinical findings has been problematic. The locus for the disorder has now been localized to a region of less than one million base pairs on the X-chromosome, permitting DNA based carrier, prenatal, and early neonatal testing for many families. The isolation and sequencing of the EDA gene itself should be forthcoming by the application of the techniques of positional cloning. The isolation of the gene will allow direct mutation detection in even sporadic cases, and will further improve genetic counseling. It will also permit analysis of how the gene functions in the normal development of the epidermal and oral ectoderm, which may result in improved therapies for the disorder. PMID- 8217563 TI - Molecular biology of the neurofibromatoses. AB - The molecular biology of the neurofibromatoses is fascinating, both because the process of obtaining the data has been instructive in investigating other genetic disorders and because those data will be so informative about physiological and pathological phenomena well beyond the neurofibromatoses themselves. In this brief overview, the highlights of the molecular biology of NF-1 and NF-2 are noted and their significance considered in terms of key clinical facts. PMID- 8217564 TI - Proceedings of the 1991 International Symposium on Data on Aging. Crosscutting issues on long-term care: introduction. PMID- 8217565 TI - Proceedings of the 1991 International Symposium on Data on Aging. Cognitive function and the elderly. PMID- 8217566 TI - Proceedings of the 1991 International Symposium on Data on Aging. Long-term care policy in international perspective. PMID- 8217567 TI - Proceeding of the 1991 International Symposium on Data on Aging. Crosscutting issues on other international research on aging: introduction. PMID- 8217568 TI - Proceedings of the 1991 International Symposium on Data on Aging. International research on healthy life expectancy. PMID- 8217569 TI - Proceedings of the 1991 International Symposium on Data on Aging. World Health Organization program for research on aging. PMID- 8217570 TI - Proceedings of the 1991 International Symposium on Data on Aging. Healthy aging. PMID- 8217571 TI - Proceedings of the 1991 International Symposium on Data on Aging. Health promotion and disease prevention workshop. PMID- 8217572 TI - Proceedings of the 1991 International Symposium on Data on Aging. Vitality workshop. PMID- 8217573 TI - Proceedings of the 1991 International Symposium on Data on Aging. Functional disability workshop. PMID- 8217574 TI - Proceedings of the 1991 International Symposium on Data on Aging. Outcomes of nursing home care workshop. PMID- 8217575 TI - Proceedings of the 1991 International Symposium on Data on Aging. Models of disability. PMID- 8217576 TI - Expanded programme on immunization. PMID- 8217577 TI - Acute flaccid paralysis surveillance, 1992. PMID- 8217578 TI - Tetanus fatality. PMID- 8217579 TI - Drug alert: halofantrine. PMID- 8217580 TI - Epidemic neuropathy. PMID- 8217581 TI - Lyme disease 1991-1992. PMID- 8217582 TI - Expanded programme on immunization. The global elimination of neonatal tetanus: progress to date. PMID- 8217583 TI - Malaria. Localized outbreak. PMID- 8217584 TI - Veterinary public health. Documents available. PMID- 8217585 TI - Influenza. Antigenic analysis of recent influenza virus isolates. PMID- 8217586 TI - Maternal and child health. Infant mortality, 1990. PMID- 8217587 TI - Long-term survival after pancreatic adenocarcinoma--often a misdiagnosis? AB - Prognosis of adenocarcinoma of the pancreas has remained poor, but a few patients are reported to live 5 years or longer after the diagnosis. Using the data of the Finnish Cancer Registry, we could identify only 78 patients (1.3%) who had survived for longer than 5 years after the diagnosis of pancreatic cancer among 5,837 patients diagnosed in Finland in 1975-1984. However, in 33 of the 78 cases a histological diagnosis of pancreatic cancer had never been made, and the majority of the remaining 45 patients turned out not to have pancreatic adenocarcinoma after a review. The results suggest that the majority of patients with long-term survival following the diagnosis of pancreatic cancer have never had pancreatic adenocarcinoma. Taking a biopsy from a suspected pancreatic neoplasm and careful histological evaluation may prohibit misdiagnosis of this highly lethal disease. PMID- 8217589 TI - Trends in lip cancer incidence in Vaud, Switzerland. AB - Recent trends in lip cancer incidence in the Swiss Canton of Vaud (approximately 600,000 inhabitants in 1990) were analysed over the period 1975-1990, when a total of 87 cases were registered. A steady and substantial decline was observed in both sexes, since age-standardised (world) rates declined from 1.8 to 0.6/100,000 males and from 0.14 to 0.02/100,000 females. These downward trends were evident across subsequent age groups. These trends were apparently not due to changes in registration or classification criteria in the study period and are discussed in terms of decreased occupational exposure to ultraviolet light, and reduced pipe and cigar smoking. PMID- 8217588 TI - Risk of second primary cancer after Hodgkin's disease in patients in the British National Lymphoma Investigation: relationships to host factors, histology and stage of Hodgkin's disease, and splenectomy. AB - The risks of second primary cancer were analysed in 2846 patients with Hodgkin's disease treated within the British National Lymphoma Investigation during 1970 87. The relative risk (RR) of leukaemia was significantly greater in women (RR = 30.1; 95% confidence limits (CL) 13.0-59.5) than in men (RR = 10.9; 95% CL 4.7 21.5), and showed a significant trend of greater risk with younger age at first treatment (P < 0.001). The relative risk of solid cancers was similar between the sexes, but again significantly greater at young than at older ages of first treatment (P < 0.01). Non-Hodgkin's lymphoma relative risks, although not related to sex or age, were significantly related to histology of the original Hodgkin's disease, and were greatest after lymphocyte predominant Hodgkin's disease (RR = 55.6; 95% CL 18.0-129.7). The relative risk of second cancers did not vary significantly according to whether or not splenectomy had been performed. Leukaemia risk was non-significantly greater after splenectomy than with no splenectomy, which accorded with previous evidence of a modest increased risk associated with this operation. If the greater relative risk of solid second cancers after treatment at young than at older ages persists with longer follow up, the incidence rates of these second primaries in patients treated young for Hodgkin's disease will become very substantial as they age. This emphasises the need to maintain long-term follow-up surveillance of young Hodgkin's disease patients apparently cured of their disease, and to continue to develop new less carcinogenic treatment regimens. PMID- 8217590 TI - Epstein-Barr virus and carcinomas: rare association of the virus with gastric adenocarcinomas. AB - We have analysed 174 gastric carcinomas from the United Kingdom and from Japan for the presence of Epstein-Barr virus (EBV) using in situ hybridisation for the small EBV-encoded nuclear RNAs (EBERs). EBV was detected in the tumour cells in all of six undifferentiated gastric carcinomas with prominent lymphoid stroma (undifferentiated carcinomas of nasopharyngeal type, UCNT) but only in three of the remaining 168 typical gastric adenocarcinomas (1.8%). No differences were observed between the British and the Japanese cases. One case with an EBV positive UCNT showed adjacent areas of EBV-negative typical adenocarcinoma. It is uncertain whether these patterns represent two independent carcinomas or whether they are the result of heterogeneous EBV infection in a single tumour. In the remaining EBV-positive carcinomas, viral transcripts were detected in virtually all tumour cells, indicating that EBV infection must have taken place early in the neoplastic process and suggesting that the virus is likely to be of pathogenetic significance for the virus-associated tumours. Immunohistology demonstrated absence of detectable levels of the EBV-encoded latent membrane protein, LMP1, and nuclear antigen, EBNA2. The BZLF1 protein which induces the switch from latent to lytic infection was demonstrated in a small proportion of the tumour cells in three cases. The close association of EBV with undifferentiated gastric carcinomas compared to the variable association with gastric adenocarcinomas suggests fundamentally different roles for the virus in the aetiology of these two malignancies. PMID- 8217592 TI - A cohort study of cystic fibrosis and malignancy. AB - A cohort of 412 patients first attending a cystic fibrosis (CF) clinic between 1961 and 1989 were followed up to 30 June 1989. The number of malignancies observed in the cohort was compared with the number expected based on the age, sex and calendar-year-specific cancer registration rates for England and Wales. Four CF patients were diagnosed as having malignancies before 30 June 1989. The tumours were: adenocarcinoma of the terminal ileum; adenocarcinoma of the pancreas, testicular teratoma, and B-cell lymphoma. This compares with 0.89 malignancies expected on the basis of rates in England and Wales (Standardised Registration Ratio = 452; 95% confidence interval 122-1150, P = 0.03). The single case of adenocarcinoma of the terminal ileum contrasts with less than 0.001 expected (P = 0.003) and that of the pancreas with 0.007 expected (P = 0.01). A further adenocarcinoma of the pancreas was diagnosed 2 years after the end of the study period. The two cases of pancreatic cancer compare with 0.008 expected (P = 0.0001) during the period to mid 1991. On the basis of the present findings and previous case reports in the literature adenocarcinoma of the pancreas and adenocarcinoma of the terminal ileum may be associated with cystic fibrosis. PMID- 8217591 TI - Inverse association of nm23-H1 expression by colorectal cancer with liver metastasis. AB - The expression of nm23-H1 mRNA and protein was studied in colorectal cancers by Northern blotting and immunohistochemistry. All 21 colorectal cancers studied by Northern blotting had increased levels of nm23-H1 mRNA relative to the adjacent normal colonic mucosa. Increased nm23-H1 protein expression was also observed in all 36 colorectal cancer cases including those studied by Northern blotting. There was no significant correlation between nm23-H1 expression and tumour histology, serosal invasion, lymphatic invasion, venous invasion, or lymph node metastasis. However, the expression of both mRNA and protein was significantly lower in tumours associated with liver metastasis than in those without such metastasis. These observations indicate that the nm23 gene may play a role in the suppression of liver metastasis of colorectal cancer. PMID- 8217593 TI - p53 immunohistochemistry in transitional cell carcinoma and dysplasia of the urinary bladder correlates with disease progression. AB - Immunohistochemically detectable p53 protein using a polyclonal antibody (CM-1) was studied in 42 carcinomas of which 11 were grade I, 22 grade II and nine grade III carcinomas. Additionally 14 urothelial dysplasias were studied. In 11 of these a diagnosis of transitional cell carcinoma was established before and in one after the dysplasia diagnosis. Twenty-one out of 42 (50%) cases of transitional cell carcinoma were positive for the p53 protein. Eleven out of 14 (78%) dysplasias and 10/12 (83%) related carcinomas were p53 positive. One out of 11 grade I (9%), 12/22 grade II (55%) and 8/9 grade III (89%) tumours showed positivity for p53. There were significantly more p53 positive cases in grade II III tumours than in grade I tumours (P = 0.004). There were significantly more p53 positive cases in stage T2-T4 tumours than in stage T1 tumours (P = 0.035). In only one case among the 11 dysplastic lesions following the treatment of a carcinoma the dysplastic lesion was p53 negative while the preceding carcinoma was p53 positive. All dysplasias and 28 carcinomas were also immunostained for laminin and type IV collagen to evaluate the continuity of basement membranes (BMs). Clearly disrupted BMs were observed only in grade III carcinomas. These cases showed the most p53 immunopositivity. The results show a strong association of p53 staining between dysplasias and transitional cell carcinomas of the urinary bladder indicating that these lesions might share similar p53 changes. The correlation to grade, clinical stage and to disrupted BM suggests that p53 mutations may be associated with the evolution of aggressive growth characteristics in transitional cell carcinomas or, alternatively, that p53 positive tumours of a more aggressive type from the start. Whether p53 staining can be used as an adjunct in the assessment and follow-up of epithelial changes of patients treated for a p53 positive bladder carcinoma deserves to be studied. PMID- 8217594 TI - Patients with metastatic renal carcinoma candidate for immunotherapy with cytokines. Analysis of a single institution study on 181 patients. AB - This study was performed with the aim of discovering the characteristics and survival of patients with metastatic renal carcinoma who undergo immunotherapy with an Interleukin 2 based regimen. One hundred and eighty-one patients with metastatic renal carcinoma were referred to our institute from October 1987 until August 1991; 129 were treated with Interleukin 2 with or without Interferon alpha in three successive protocols. Fifty-two patients were not treated with immunotherapy due to the exclusion criteria of the protocols. Sixty-four patients with the same disease who had been referred to our institute before the initiation of this programme (1982, 1987) were also analysed as a control group. The main characteristics of the three different cohorts of patients were analysed and compared with univariate statistical tests; the median survival of the patients was calculated and compared. The referral rate increased from 13 a year to 45 a year while the IL2 trials were being conducted. Patients treated with cytokines have a median survival of 18 months after occurrence of metastases, compared to 6 and 8 months, respectively, in excluded patients and the control group. This parameter is of 15 months when the 181 patients, treated with cytokines or not, are considered. The survival of treated vs excluded patients is significantly different (P < 10(-6); so is the survival of the 181 patients recently included when compared to the historical group (P:10(-5). When the 181 recent patients are compared to the historical control group, a number of differences appear in their characteristics, which prevent us from drawing any conclusion about the role of immunotherapy in the improvement of survival observed. This study clearly evidences the selection of the patients receiving immunotherapy and the modification in referrals of a disease induced by a new available therapy. This emphasises the need for prospective studies in this setting. PMID- 8217595 TI - Reliability of cancer registry records. PMID- 8217596 TI - Pathology review in cancer research. AB - Pathology observer agreement studies are clearly important in the development of new pathology assessments and in the quality control of those assessments in common use. Setting up such studies, and reporting and interpreting their results requires careful thought and statistical expertise. Investigators are advised to seek collaboration with a statistician before embarking on these studies. Pathology reference panel reviews in multicentre studies are useful for checking eligibility when there is a high level of disagreement on the eligibility criterion between local pathologists and the reference panel members, but good agreement between members of the panel. However, such situations are uncommon. PMID- 8217597 TI - Characterisation of a new mouse monoclonal antibody (ONS-M21) reactive with both medulloblastomas and gliomas. AB - We developed an IgG1 mouse monoclonal antibody (ONS-M21) directed against a cell surface antigen of medulloblastomas and gliomas in immunisation of mice with the ONS-76 medulloblastoma cell line. The antibody specifically reacted with medulloblastomas, supratentorial primitive neuroectodermal tumours (SPNETs) and gliomas, but not with other neuroectodermally derived tumours (neuroblastoma and melanoma) or with other kinds of tumours (meningioma, neurinoma, leukaemia, and small cell lung cancer). No reactivity was identified with normal body tissues, including peripheral blood cells. Characterisation of the ONS-M21 antigen showed that it was a trypsin-sensitive glycoprotein with a molecular weight of 80 kDa on SDS-PAGE. The pattern of reactivity and the biochemical properties of this antigen were different from those of other markers of medulloblastoma. These results indicate that ONS-M21 detects a new tumour-associated cell surface antigen specifically expressed by medulloblastomas, SPNETs, and gliomas. This is the first report that medulloblastomas may share common cell surface antigens with gliomas, although most studies have concluded that medulloblastoma has a predominantly neuronal phenotype. The lack of reactivity with normal tissue implies that ONS-M21 has potential applications as both a diagnostic tool and a therapeutic agent. PMID- 8217598 TI - Hyperresistance to 4-nitroquinoline 1-oxide cytotoxicity and reduced DNA damage formation in dermal fibroblast strains derived from five members of a cancer prone family. AB - Dermal fibroblasts cultured from members of a family presenting multiple polyps and sarcomas were compared with fibroblast strains from unrelated healthy donors for sensitivity to killing by four genotoxic agents. Cells from the sister of the male proband (strain 3437T), mother (strain 3703T), two of his paternal aunts (3701T and 3704T) and one paternal uncle (3702T) displayed marked resistance (1.8 to 4.3 times greater than the normal mean) to 4-nitroquinoline 1-oxide (4NQO), a procarcinogen whose DNA-damaging properties encompass those of both far (254 nm) ultraviolet (UV) light and ionising radiation. These same 4NQO-resistant cells, however, responded normally to reproductive inactivation by UV light, 60Co gamma radiation or the alkylating agent methylnitrosourea, signifying that the abnormal resistance of these cells to 4NQO is not associated with aberrant DNA metabolism. In keeping with this conclusion, exposure to a given dose of 4NQO produced decreased amounts of DNA damage and stimulated lower levels of repair DNA synthesis in all five 4NQO-resistant strains than in normal controls. Moreover, exogenous radiolabelled 4NQO accumulated to a lesser extent in the 4NQO-resistant than in the normal fibroblasts. Cell sonicates of strains 3437T, 3701T and 3702T exhibited reduced capacities (40-60% of normal) to catalise the conversion of 4NQO to the proximate carcinogen 4-hydroxyaminoquinoline 1-oxide. However, the 4NQO-resistant strains 3703T and 3704T carried out 4NQO bioreduction at normal rates. Our data therefore indicate that enhanced resistance to 4NQO cytotoxicity in 3437T, 3701T and 3702T is a consequence of anomalies in both intracellular accumulation and enzymatic reduction of 4NQO, whereas 4NQO resistance in 3703T and 3704T appears to result solely from reduced intracellular drug accumulation. PMID- 8217599 TI - Retinoids, breast cancer and NK cells. AB - N-(4-hydroxyphenyl) retinamide (4-HPR) is a synthetic retinoid which reduces the incidence of experimental tumours in animals and has been chosen for its weak toxicity to be tested as a chemopreventive agent in humans. The mechanism of antineoplastic action is still unknown but a possible immunoenhancing effect may be postulated. We investigated the NK activity of PBMC from a group of women treated with 4-HPR as a part of a large scale randomised phase III trial on chemoprevention of contralateral disease in mastectomised women. After 180 days of treatment the NK activity was augmented 1.73 times as compared to that of patients given a placebo. The NK activity of PBMC from 4-HPR treated women is maximised, being higher than the basal and even the rIL-2 or alfa-rIFN stimulated activity of controls. For this reason in the majority of cases it cannot be further augmented by incubation with either rIL-2 or alfa-rIFN in vitro. The increased NK activity of 4-HPR treated women is not due to an enhanced production of endogenous IL-2, because PBMC cultures from patients treated with 4-HPR or placebo, incubated in vitro with a panel of different stimulators (recall antigens, PHA, allogeneic and xenogeneic cells) produce similar amounts of IL-2. The functional activity, but not the number of NK cells is increased in 4-HPR treated women. The mechanism by which 4-HPR stimulates NK activity is not a function of direct action on NK cells. Indeed incubation of PBMC from blood donors with 4-HPR or its major metabolite N-(4-methoxyphenyl) retinamide (4-MPR) does not modify their natural cytotoxicity. PMID- 8217600 TI - Expression of different conformations of p53 in the blast cells of acute myeloblastic leukaemia is related to in vitro growth characteristics. AB - Expression of the wild-type p53 gene has an important role in cell differentiation, maturation and apoptosis. Mutation of the p53 gene is associated with tumour development and mutant p53 can promote cell proliferation. Recently wild-type p53 has been demonstrated to exist in two conformational variants: one acting as a suppressor (PAb240-/PAb1620+) and one as a promoter (PAb240+/PAb1620 ) of cell proliferation. We have analysed the expression of p53 by flow cytometry in blast cells from 34 patients with acute myeloblastic leukaemia in relationship to the proliferation characteristics of these cells in a clonogenic assay. Blasts from three out of 34 patients did not express p53 using the antibodies: PAb421, PAb1801, PAb240 and PAb1620. The remaining 31 samples expressed p53 detected by PAb240 which recognises mutant p53 and is predicted to recognise wild-type p53 in the promoter conformation. Blasts from 19 out of 31 cells which expressed PAb240 co-expressed PAb1620, expression of PAb1620 was associated with non-autonomous growth in vitro. In contrast, the majority of blasts with the p53 phenotype of PAb240+/PAb1620- or which lacked p53 expression exhibited autonomous growth characteristics in vitro. Furthermore expression of PAb1620 in blasts with autonomous growth cells could be detected following growth inhibition using monoclonal antibodies against autocrine growth factors. Our data demonstrate that in AML cells, p53 conformation is related to the growth characteristics of the cells and is regulated by either exogenous or autocrine haematopoietic growth factors. PMID- 8217601 TI - A novel cell-based assay for the evaluation of anti-ras compounds. AB - In order to identify drugs active against mutated ras oncogenes we have developed an in vitro assay employing two clones of the human fibrosarcoma cell-line, HT1080 which carries an N-ras gene mutated at codon 61. Clone, HT1080scc2, retains the transformed phenotype of the parental line, whilst the other, HT1081c, is a morphologically flat, non-tumourigenic, revertant with under representation of the chromosome carrying the transforming N-ras allele. The clear implication of mutant ras in maintaining the transformed nature of HT1080scc2 was confirmed when these cells were microinjected with the pan ras neutralising antibody Y13-259, which resulted in the morphological detransformation of these cells to a phenotype resembling that of the HT10801c clone. A number of known anti-cancer drugs with modes of action unrelated to ras function were found to be equipotent against both clones. However, when compounds chosen on the grounds of their potential selective cytotoxic or differentiating activity were tested some interesting results were obtained. Thus 8-bromo cAMP affected some morphological detransformation of HT1080scc2 cells and reduced their colony forming potential. The IMP-dehydrogenase inhibitors, tiazafurin and mycophenolic acid also flattened the morphology of the transformed clone. Fumagillin, an antibiotic reported to exhibit selective activity against ras transformed cells showed very marked and selective cytostatic effects against HT1080scc2 cells with IC50 values as low as 1 x 10(-11) M. PMID- 8217602 TI - Malignant progression of SV40-immortalised human milk epithelial cells. AB - A human breast epithelial cell line (Hu-MI), established by microinjecting SV40 DNA into human milk epithelial cells, exhibits the phenotype of luminal epithelial cells and is neither clonogenic nor tumorigenic. From this cell line we have selected two sublines, HuMI-T and HuMI-TTul, reflecting different stages of spontaneous transformation. HuMI-T cells grow anchorage-independently, but do not induce tumours in nude mice. HuMI-TTul cells are clonogenic as well as tumorigenic. Cells from both lines exhibit polymorphic structural and numerical chromosome aberrations. Immortalisation of normal luminal epithelial cells from human mammary gland with SV40 DNA alone may thus cause random genetic changes eventually resulting in tumorigenic cell lines. Since Hu-MI, HuMI-T and HuMI-TTul represent some of the consecutive stages taking place during cellular transformation, they are particularly suited as a novel in vitro model system to study progression of human breast cancer. PMID- 8217603 TI - Expression of the nm23-2/NDP kinase alpha gene in rat mammary and oral carcinoma cells of varying metastatic potential. AB - Reduced expression of the putative metastasis-suppressor gene, nm23-1, has previously been correlated with high tumour metastatic potential. The involvement of the related and proximally-located nm23-2 gene in the suppression of tumour metastasis, however, has not yet been tested. In this study, we compared nm23-2 RNA levels in cell lines derived from three independent rat mammary carcinomas. Northern blot analysis revealed no correlation between nm23-2 RNA levels and metastatic potential in parent or clonal cell lines derived from chemically induced (MAT 13762, DMBA-8) or spontaneous (BC1) rat mammary carcinomas. Cloning and sequencing of an nm23-2 cDNA from metastatic BC1 cells demonstrated that the predicted coding sequence of nm23-2 RNA in these cells was not inactivated by mutation. Further analysis showed that the nm23-2 gene was not down-regulated in H-ras-transfected metastatic clones or other metastatic cell lines derived from a spontaneous rat paraoral squamous cell carcinoma, B10. The data do not suggest a correlation between nm23-2 gene expression and metastasis-suppression in these tumours. PMID- 8217604 TI - Body protein and lipid deficit in tumour-bearing rats in relation to age. AB - Cancer cachexia is among the most dramatic situations of depletion in body energy reserves. To ascertain whether the pattern of body composition alteration during tumour development is influenced by aging as in uncomplicated starvation, we compared the difference of body composition between Yoshida sarcoma bearing rats and young (200 g, 7 weeks) and adult (400 g, 13 weeks) control rats. After the same duration of tumour bearing, mass and composition of tumours were similar in adult and young rats, indicating that they are independent of host age. Food intake decreased to a remarkably similar value in both young and adults. Body water content was elevated in hosts of both ages. The relative deficit of body lipid vs controls was similar for both, the absolute lipid deficit being therefore larger in adult than in young tumour-bearing rats (14.3 +/- 4.4 g vs 6.8 +/- 0.9 g; P < 0.01). In contrast, there was a relatively larger deficit of body protein in young rats. Paradoxically, these rats still maintained a positive nitrogen balance whereas this balance was negative in adult tumour-bearing rats. In conclusion, as previously shown in uncomplicated undernutrition, the anorexia induced by Yoshida sarcoma development is still associated with some protein accretion in young rats whereas cachexia develops in adults. PMID- 8217605 TI - Regulation of intracellular pH in subpopulations of cells derived from spheroids and solid tumours. AB - Solid tumours are known to develop regions of extracellular acidity and survival of tumour cells in such regions depends on membrane-based mechanisms which regulate intracellular pH (pHi). We have therefore developed a method, based on dual staining of cells and flow cytometry, to study the regulation of pHi in subpopulations of tumours and spheroids. The activity of membrane-based pHi regulating transporters was studied in EMT-6 and MGH U1 cells grown in monolayer culture, spheroids, and tumours. pHi was measured with the fluorescent pH probe 2'7'-bis-(2-carboxyethyl)-5-(and-6)carboxyfluorescein, and Hoechst 33342 was used to identify cells from different regions of tumours and spheroids. In monolayer culture, incubation of cells for 18 h at pHe 6.6 led to a 1.3-1.5-fold enhancement in the activity of both the Na+/H+ exchanger and the Na(+)-dependent Cl-@HCO3- exchanger. This effect was prevented by the protein synthesis inhibitor cycloheximide. Cells from the centre of EMT-6 spheroids had increased activity of the Na+/H+ exchanger compared to cells from the periphery, when spheroids were grown in medium at pH 6.6, but not at 7.4. By contrast, in MGH U1 spheroids, cells from the centre had increased activity of the Na+/H+ antiport under both sets of conditions. There was no significant difference in the activity of the Na+/H+ exchanger in cells derived from different subpopulations of EMT-6 tumours or MGH U1 xenografts in nude mice. Although upregulation of Na+/H+ exchange occurs after exposure to acidic conditions in vitro, the microenvironmental conditions found within solid tumours do not appear to cause this effect. Our results suggest the feasibility of pharmacological inhibition of Na+/H+ exchange activity as an approach to therapy directed against nutrient-deprived tumour cells. PMID- 8217606 TI - Enhancement of tumorigenicity of human breast adenocarcinoma cells in nude mice by matrigel and fibroblasts. AB - The failure of MCF7 cells to induce the formation of tumours after sub-cutaneous inoculation into athymic nude mice can be obviated by the simultaneous injection of an extract of basement membrane proteins (matrigel). Tumour growth is promoted and the latency period is low (2 to 4 weeks). In the absence of matrigel, the simultaneous inoculation of fibroblasts and MCF7 cells also resulted in the development of tumours, but with a longer latency period (about 2 months). The tumorigenic synergy between matrigel and fibroblasts was evidenced by co inoculating MCF7 cells MDA-MB 231 cells with fibroblasts and matrigel. This co inoculation decreased the delay of appearance of the tumours and/or accelerated the tumour growth, depending upon the number of fibroblasts injected. Repeated injections of fibroblasts conditioned medium, at the site of inoculum of tumour cells also enhanced tumour growth, suggesting the involvement of soluble factors secreted by fibroblasts. Histologically, tumours induced by co-inoculation of tumour cells and fibroblasts contained more stromal structures including vimentin positive cells, fibronectin and interstitial collagens. These data suggest that human tumours may be reconstituted and grown in athymic nude mice using basement membrane components and fibroblasts as inductors. PMID- 8217607 TI - Similarity and co-expression of tumour-associated antigens recognised by different monoclonal antibodies. AB - The concentration of carcinoembryonic antigen (CEA), CA130, CA125, SLX, CA19-9, SPan1, and tumour-associated glycoprotein 72 (TAG-72) in the culture supernatant of 15 cancer cell lines and in the sera of 58 cancer patients was measured, and the co-expression of these antigens was examined by double determinant immunoradiometric assays. The high correlation coefficient of the concentrations and significant binding in the double determinant assays indicated a close relationship between CA125 and CA130 and between CA19-9 and SPan1. There was variable binding of the 125I-labelled anti-SLX, anti-CA19-9, and anti-SPan1 antibodies to anti-CA130 beads that had been pre-incubated with the culture supernatants, suggesting the presence of the epitopes of SLX, CA19-9, and SPan1 on the molecule expressing CA130. Similarly, the epitopes of SLX, CA19-9, and SPan1 could be present on the molecule expressing CEA. 125I-labelled anti-CA19-9, anti-SLX, and anti-TAG-72 antibodies were bound in variable proportions to anti CA130 beads or to anti-CEA beads that had been pre-incubated with patients' sera. However, CEA and CA130 were not expressed on the same molecule, either in the culture supernatant, or in patients' sera. In conclusion, the carbohydrate epitopes of CA19-9, SPan1, SLX, and TAG-72 could be present on the molecule recognised by the anti-CA130 or anti-CEA antibody; however, the epitopes of CA130 and CEA did not co-exist on the same molecule. PMID- 8217608 TI - Epithelial mucin core antigen (EMCA) in assessing therapeutic response in advanced breast cancer--a comparison with CA15.3. AB - We report a comparative study of CA 15.3 and EMCA (epithelial mucin core antigen) in 77 consecutive women with newly diagnosed UICC assessable metastatic breast cancer, 59 patients received hormones and 18 chemotherapy. Assessments of response were made prior to commencing therapy and repeated 2 monthly. Sites of metastatic disease included bone (34), pulmonary (8), bone and pulmonary (14) and visceral (21). Using a cut-off of 33 U ml-1 changes in EMCA at 2, 4 and 6 months showed a highly significant correlation (P < 0.001) with UICC assessed response at 6 months; selectivity 70%, sensitivity 80%, specificity 91%, positive predictive value 84%; negative predictive value 89% at 2 months. Corresponding values for CA 15.3: selectivity 89%, sensitivity 85%, specificity 91%, PPV 92% and NPV 91%. Four of eight patients unassessable by CA 15.3 were assessable by EMCA; four patients expressed neither marker. EMCA appears to reflect tumour bulk and may be useful in monitoring therapy in patients with advanced breast cancer. With an easier and more robust assay format than CA 15.3, EMCA is potentially a more useful marker. PMID- 8217609 TI - Mechanisms of oncogenesis in patients with familial retinoblastoma. AB - In an analysis of mutations in the RB1 gene in three patients, selected at random, who had a positive family history of tumours, we identified mutations, in constitutional cells, involving exons 3, 13 and 17 of the RB1 gene. We used SSCP and PCR sequencing to screen affected individuals and other members of their families. In two cases the mutations were 2 bp and 1 bp deletions identified in exons 3 and 17 respectively. The third mutation was a 1 bp insertion in exon 13. All three mutations lead to the generation of downstream premature stop codons as a result of frameshift changes, although the mutation in exon 3 possibly affects the splicing mechanism. The sites within the RB1 gene where these mutations occur contain interspersed repetitive DNA sequences, direct and inverted repeat sequences and/or dyad symmetrical elements suggesting that these areas promote the appropriate local sequence environment for the generation of deletions and insertions in the RB1 gene. PMID- 8217610 TI - Screening and the costs of treating colorectal cancer. AB - The objective of this paper is to compare the hospital costs of treating patients with colorectal cancers detected as a result of a faecal occult blood screening programme with those of patients whose cancers present symptomatically (control group). Patient-specific cost estimates are made, using case records and hospital accounts, for 360 patients over 3 years. Mean treatment costs for the group offered screening and for the control group are calculated to be 3,179 pounds and 2,966 pounds respectively, although the difference between these means is insignificant. Low treatment costs in the case of screen-detected cancers are largely accounted for by polypectomy with no subsequent readmission; in the control group case, they tend to be accounted for by early patient death. For the sample as a whole, the costs of treating very early-, and very late-, stage cancer are significantly lower than those of treating cancers in the intermediate stages. On the basis of trial evidence, the introduction of mass screening for colorectal cancer is unlikely to give rise to substantial economies in the costs of treatment. PMID- 8217612 TI - Quality of cancer registry data: a comparison of data provided by clinicians with those of registration personnel. AB - The quality of cancer registry data is of great importance to the usefulness of a cancer registry. To investigate the quality of its data the IKL cancer registry (Integraal Kankercentrum Limburg) performed a study with the aim of comparing data supplied by clinicians with data collected by registration personnel. Twenty clinicians reabstracted the information of a random sample of about ten of their patients, who were diagnosed with cancer in 1989 or 1990. After coding, the information was compared with the contents of the cancer registry records. For comparison of agreement the information of 190 cases was available. The relative frequency of major disagreements was 0% for date of birth, 0% for gender, 5% for date of incidence, 6% for primary site, 2% for laterality, 2% for histologic type and 2% for behaviour code. In general, the disagreements could be attributed to the handling of different coding rules (incidence date), or to a lower level of precision by the clinician in comparison to registration personnel (primary site, laterality). This study has shown that registration personnel are able to collect data with a high degree of accuracy. PMID- 8217611 TI - Spinal cord compression in breast cancer: a review of 70 cases. AB - Spinal cord compression (SCC) is a relatively uncommon but frequently disabling complication of metastatic breast cancer. We have conducted this retrospective study of 70 patients with SCC secondary to breast cancer with the aims of determining risk factors for its development and predictors of outcome. Median age at diagnosis of breast cancer was 51 years with median time to SCC 42 months. All patients had radiological evidence of bone metastases at the time of SCC, and only five were not known to have bone metastases prior to SCC. The most frequent symptom of SCC was motor weakness (96%) followed by pain (94%), sensory disturbance (79%) and sphincter disturbance (61%). Ninety-one percent of patients had at least one symptom for more than a week. Radiotherapy (RT) was given as primary treatment in 43 cases, whilst 21 had decompressive surgery and seven of these went onto have postoperative radiotherapy. Six patients were deemed too unwell for either modality. Following treatment, 96% of those who were ambulant before therapy maintained the ability to walk. In those unable to walk, 45% regained ambulation, with RT and surgery being equally effective. Median survival following SCC was 4 months, with no significant difference between those treated by RT or surgery. The most important predictor of survival was ability to walk after treatment, followed by time from diagnosis of breast cancer to SCC. We conclude that the majority of patients have warning symptoms of SCC and that nearly all will have evidence of spinal bone metastases before compression occurs. The results suggest that earlier diagnosis and intervention could improve outcome. There was no evidence of benefit from surgery over radiotherapy as primary treatment, survival in both treatment groups being poor. PMID- 8217613 TI - Declining incidence is greater for esophageal than gastric cancer in Shanghai, People's Republic of China. AB - Temporal trends in the incidence of esophageal and gastric cancers during 1972 to 1989 were addressed in urban Shanghai, the location of China's longest standing cancer registry. Over the 18 year study period, esophageal cancer rates decreased more than 50% from 28.8/100,000 person-years in 1972-74 to 13.3/100,000 in 1987 89 among men and from 11.3/100,000 to 5.4/100,000 among women. Reductions were apparent in each age group, but most pronounced among younger generations, with more than a 75% decline in incidence among those under age 55 years. The incidence rate for stomach cancer among men decreased 20% from 62.0/100,000 in 1972-74 to 50.1/100,000 in 1987-89. The reduction among women, however, was minor, from 23.9/100,000 to 23.2/100,000. The patterns varied by age, with declines among persons 45-64 years and increases among those in older and younger age groups. The determinants of these trends are not clear, but appear related in part to dietary changes. PMID- 8217614 TI - Repeat administration of high dose melphalan in relapsed myeloma. AB - At a median time of 20 months following high dose melphalan for myeloma, 29 patients relapsed and were treated with induction chemotherapy to maximum response followed by a second course of high dose melphalan. The majority (90%) of patients received 200 mg m-2 with an autologous bone marrow transplant. Sixteen (55%) patients achieved complete remission and 11 (38%) a partial response. The median duration of remission was 17 (4-42) months. The median survival has not been reached, with 50% of patients alive at 58+ months after presentation. The period of neutropenia was similar during both first and second high dose procedures, but the duration of thrombocytopenia was longer in patients receiving melphalan for a second time (median 22 (16-56) days and 41 (18-69) days respectively). There was one treatment-related death due to thrombocytopenic haemorrhage. Repeated administration of high dose melphalan is a feasible approach for patients with relapsed myeloma. PMID- 8217615 TI - Chemotherapy of advanced breast cancer: outcome and prognostic factors. AB - The outcome for 758 consecutive patients who had received one or more chemotherapy regimens for recurrent or metastatic breast cancer is presented. The response rate following first line treatment was 34%. Median duration of response was 7.8 months, median time to progression was 3.7 months and median survival was 7.9 months. The only factor predicting for response, of factors recorded at presentation and at initiation of chemotherapy, was the use of anthracycline based regimens, though this may reflect the patient selection policy. Initial disease free interval, presence of liver metastases and use of anthracyclines were significantly related to time to progression. Several factors related to survival following first chemotherapy, but anthracycline usage showed only a very weak correlation. One third of patients (249/758) received two or more chemotherapy regimens. The response rate (16%) and median time to progression (2.3 months) were significantly worse than for first line treatment. The outcome after third line chemotherapy was very similar to that observed following second line treatment. Achievement of an objective response with first line chemotherapy predicted for second response, but with insufficient power to be of use in selecting patients for subsequent chemotherapy. Time to progression following first line chemotherapy did not influence that after second line treatment. PMID- 8217616 TI - HIV/AIDS. Behind the wire. PMID- 8217617 TI - Infectious diseases. Beyond textbooks. PMID- 8217618 TI - Primary care: leader of the band. PMID- 8217619 TI - Nursing abroad: chairs on the move. Interview by Charlotte Alderman. PMID- 8217620 TI - Religious belief and attitudes to HIV/AIDS. AB - This article discusses a research study into the effect of religious beliefs on attitudes to HIV/AIDS. The author sought to clarify the issues involved and to discover which 'elements' within a religious belief tend to dispose the adherent to negative attitudes towards a person with HIV/AIDS. Only 6 per cent of the variation in the subjects' attitudes, however, was attributable to the degree of scriptural influence in their lives. PMID- 8217621 TI - Children's nursing: lessons from the past. AB - This article traces the development of paediatric nursing and looks at the reasons why paediatric nurses have traditionally needed a dual qualification in adult nursing. The author argues that it is time paediatric nursing was regarded as separate from adult nursing and qualifications in both adult and children's nursing as unnecessary. PMID- 8217622 TI - Balancing costs and staff commitment. PMID- 8217623 TI - Research and rescue. PMID- 8217624 TI - Nurse development: move over Wellington. PMID- 8217625 TI - Workwise. Decimation by delegation. PMID- 8217626 TI - Night shifts: good night nurses? PMID- 8217627 TI - One minute wisdom. How foreign nurses find work in Japan. PMID- 8217628 TI - Computer reviews. The mail snip. PMID- 8217629 TI - A growing concern: bacterial vaginosis (continuing education credit). PMID- 8217630 TI - Call for joint sex education. PMID- 8217631 TI - Government HIV/AIDS policy 'in disarray', claims Labour. PMID- 8217632 TI - World news. Uganda: deaths from AIDS. PMID- 8217633 TI - Stress management: getting stress taped. PMID- 8217634 TI - Developing countries: imbalance in care. PMID- 8217635 TI - Family planning: better training for practice nurses. PMID- 8217636 TI - Setting up a day unit in ophthalmology. AB - This article describes the setting up of an ophthalmic day unit for the care of adults and children undergoing eye surgery. The author outlines the steps taken in implementing a day surgery policy and describes the nursing care provided for these patients. PMID- 8217638 TI - Improving nursing records with audit. AB - This article describes the efforts of one unit to introduce an audit tool to measure the effectiveness of nursing documentation. After two years of use, the authors have been able to show that the quality of documentation is significantly better and patients have benefited from the improved communication that has resulted. PMID- 8217637 TI - Functional ability of very elderly people. AB - This article, which expands on the research discussed four weeks ago in Nursing Standard, describes the circumstances of very elderly people with different levels of functional ability, and how their ability's changed over a 2.5 year period. In particular, it focuses on the needs of those with poor functional ability, who were found to be more likely to have health problems, poorer emotional well-being, almost no friends in their social networks, and greater needs for help (or more help) from services such as chiropody. Few received services specific to rehabilitation and social support, although this group were more likely to receive a greater amount of help, in terms of instrumental aid, with tasks of daily living. PMID- 8217639 TI - Casualty: accident and non-urgency. PMID- 8217640 TI - Sister Susie. Going way out of bounds. PMID- 8217642 TI - Standards of care: scarred by nurses. PMID- 8217641 TI - Workwise. Kids? Tough. PMID- 8217643 TI - One minute wisdom. You don't have to strike to take industrial protest action. PMID- 8217644 TI - Computer reviews. A powerful Paradox. PMID- 8217645 TI - HIV guidelines under attack. PMID- 8217646 TI - HIV/AIDS. Unique help centre. PMID- 8217648 TI - Psychiatric station. Interview by Mike George. PMID- 8217647 TI - Magnet hospitals, attractive hospitals? PMID- 8217649 TI - NHS reforms: crisis of closure. PMID- 8217651 TI - Cost of absent nurses. PMID- 8217650 TI - Nutritional support for critically ill patients. AB - The incidence of malnourishment in medical and surgical patients is well documented, yet it is obvious that sufficient and appropriate nourishment is as vital to life as the maintenance of effective respiration. The effects of malnourishment are seen in all systems of the body, and cause diminutions in mental and emotional well-being. The highly compromised states of critically ill patients places them at great risk from the adverse effects of sub-nutrition, and much responsibility lies with nurses in intensive care units (ICUs) to ensure such patients are protected. This article considers the key aspects of the nurse's role in the provision of artificial nutrition to adult patients in ICUs who are, by definition, critically ill. PMID- 8217652 TI - Discharge planning for elderly patients. AB - Discharge planning for older patients is gaining recognition as a process requiring improvement. Demographic changes have produced an increasing population of elderly patients in the acute hospital sector, many of whom need co-ordinated discharge planning and appropriate post-discharge support. This article discusses the accumulated research findings of the past 20 years, which have highlighted the need for health services research, policy and practice to improve the effectiveness of discharge planning for elderly people. PMID- 8217653 TI - Preceptorship: is it a workable concept? AB - Preceptorship has many advantages to offer newly graduated nurses. The author of this article warns, however, that the mistakes made in mentorship should be heeded and its use in practice evaluated thoroughly before it is adopted without question. PMID- 8217654 TI - The implications of patient focused care. AB - There has been an increasing amount of discussion over recent months about patient focused hospitals. This article, the first of two, looks at the background to this concept and how one hospital Trust, the Central Middlesex, set about adapting it to its own needs. The implications for the delivery of patient care and changes in the nurse's role are discussed. Next week, the implementation of care protocols are covered in more detail. PMID- 8217655 TI - No limits. Mature students: part-time love. PMID- 8217656 TI - No limits. Project 2000: born in the P2K. PMID- 8217657 TI - No limits. Traditional courses: the case of the missing tutors. PMID- 8217658 TI - No limits. Equal opportunities: large scale discrimination. PMID- 8217659 TI - Approaching with care: violence at work (continuing education credit). AB - Violence against nurses, midwives and health visitors is much more common than is generally supposed or admitted. With care, by using appropriate strategies, violent and aggressive incidents can be prevented or managed, to minimise harm to all concerned. Staff support during and following an incident is vital. PMID- 8217660 TI - Magnet hospitals. Attractive hospitals? Part 2. PMID- 8217661 TI - Myalgic encephalomyelitis: continuing the debate. PMID- 8217662 TI - Nursing journals: are nurses using them? AB - This article describes a study to ascertain nurses' views on the role of professional journals and whether they make full use of this resource. Nearly three-quarters of nurses claimed they read journals on a monthly basis or more frequently, and valued nursing journals as a means of keeping up-to-date professionally. Most nurses also agreed that the study of current professional literature positively influenced their clinical competence. Such attributions support the view that the reading of journals should be an accredited method of learning. PMID- 8217663 TI - Elderly housebound: changes over time. AB - This article, which completes the research discussed in recent articles in Nursing Standard (1, 2), describes the changes in the ability of very elderly frail people to go outdoors. The sample members were first interviewed in 1987 when they were aged 85 or over, and followed up in 1990. Cross-sectional analyses showed that the groups who could not get outside alone or at all in either 1987 or 1990 were more likely to be taking prescribed medication, had poorer functional ability, reported problems with eyesight and aches/pains/stiffness in muscles/joints, had poorer emotional well-being, spent most of their days 'just sitting', and wanted more help with activities of daily living. There were, however, no differences in their social network characteristics, or their use of services. PMID- 8217664 TI - Planning individual care with protocols. AB - The introduction of patient focused care at the Central Middlesex Hospital NHS Trust is well under way. This second article discusses the implementation of one of the key elements of the change, care protocols. From the documentation changes already adopted, the team are now able to show a 30 per cent overall reduction in time spent documenting care. PMID- 8217665 TI - Hooray, we can't win. PMID- 8217666 TI - Square eyes: I hate that Casualty. PMID- 8217667 TI - Working parents: childcare's ruff deal. PMID- 8217668 TI - EuroQuan. Releasing the pressure. PMID- 8217669 TI - EuroQuan. BSI: developing the best in care. PMID- 8217670 TI - EuroQuan. Funding from the EC. PMID- 8217671 TI - EuroQuan. Accountable for quality. PMID- 8217672 TI - EuroQuan. Testing QA the European way. PMID- 8217673 TI - EuroQuan. Networking in Germany. PMID- 8217674 TI - EuroQuan. Is anybody out there listening? PMID- 8217675 TI - Suggested optimum dose of zidovudine. PMID- 8217677 TI - Pay: playing the percentages. PMID- 8217676 TI - Vision for success. PMID- 8217678 TI - Magnet hospitals. Attractive hospitals? Part 3. PMID- 8217680 TI - Advocacy: the nurse's responsibilities. PMID- 8217681 TI - Speak out and fight back. PMID- 8217679 TI - Managing malignant ulcers effectively. AB - This article aims to bring together current methods of research, thinking and practice related to the treatment and care of patients with a malignant ulcer. With appropriate care and treatment, interventions can effectively decrease social isolation and anxiety while increasing cosmetic comfort for the sufferers of this distressing problem. It is important to stress that the psychological support and interventions offered to this client group are of equal importance as the level of physiological treatment and care. PMID- 8217682 TI - Back to the future: a return to nursing. AB - With the financial constraints currently imposed on the NHS, Return to Nursing (ENB 902) courses may offer a viable method of providing mature nurses who have already been trained to cash-starved hospitals. This article describes a study examining the experiences of students on a return to nursing course and offers some suggestions for improving the course. PMID- 8217683 TI - Paying the price of job satisfaction. PMID- 8217684 TI - Stress and burnout in psychiatric nursing. AB - The purpose of this literature review is to focus on the issue of occupational stress in psychiatric nursing and to examine academic work related to the concepts of stress, coping and burnout. The review concludes with comments on the implications for nursing practice, education, research and management. PMID- 8217685 TI - Workwise. Nurse in homes. PMID- 8217686 TI - Sue Mowatt: an outgoing leader. Interview by Trevor Clay. PMID- 8217687 TI - AIDS focus. One less pain. Interview by Charlotte Alderman. PMID- 8217688 TI - AIDS focus. A unique course in mental health. PMID- 8217689 TI - AIDS focus. A partnership in caring. PMID- 8217690 TI - AIDS focus. What's on. PMID- 8217691 TI - Nurses 'ignore HIV protection'. PMID- 8217692 TI - High purity factor VIII and immune state in HIV. PMID- 8217694 TI - Health reforms: coming to the boil. PMID- 8217693 TI - Commitment to quality. PMID- 8217695 TI - Early detection of postnatal depression. AB - Although postnatal depression is considered a relatively common problem, it is particularly difficult to detect in the early months following childbirth. The author describes how she and her colleagues examined what action could be taken to increase the detection of postnatal depression in the early stages, and benefited from the use of the Edinburgh Postnatal Depression Scale. While she concedes that the project would need to be developed into a wider study before definitive conclusions could be drawn, the article demonstrates how different parts of the primary health care team can work together to improve services to patients. PMID- 8217696 TI - Elderly care: meeting the needs of ethnic patients. AB - This article describes the attempts of a nursing development unit to address the difficulties of providing care for the increasing population of elderly people from ethnic minorities. The specific problems that occur and the measures introduced to combat them are highlighted, and the unit's plans for further improvement are outlined. PMID- 8217697 TI - Israeli quality survey: research 'spin-offs'. AB - Quality assurance surveys in nursing are worthless unless the results can be translated into practical action. The author demonstrates how one such survey in Israel inspired Masters' students at Tel Aviv University to base their projects and theses on the survey findings, and produced intervention models and tools for improving care in several important areas of nursing. Encouraging the students to conduct these studies as 'spin-offs' from a major piece of national research has fostered a much broader understanding of quality assurance which has had a direct impact on patient care, and provides an example which nurses, educators and students in other countries can emulate. PMID- 8217698 TI - Workwise. Background injured nurses. PMID- 8217699 TI - Education: your first death shouldn't be the last. PMID- 8217701 TI - Sister Susie. Bounding up, down and out. PMID- 8217700 TI - One minute wisdom. Elderly care home residents should not be forced to adopt healty lifestyles. PMID- 8217702 TI - Nurse yourself. PMID- 8217703 TI - The Standard guide to ... professional portfolios and profiles. PMID- 8217704 TI - Computer reviews. Getting over the style. PMID- 8217705 TI - Streetwise but clinic-shy. PMID- 8217706 TI - Information technology: terms and conditions. PMID- 8217707 TI - Secondary sexual abuse. PMID- 8217708 TI - Sexual abuse: giving support to nurses. AB - Nurses dealing with people who have been sexually abused as children need strong support and supervision systems to enable them to cope with the feelings of helplessness and sadness that can arise. Such a system has been set up at a psychiatric day hospital in London to help nurses provide consistent, long-term and non-judgemental care. PMID- 8217709 TI - Enrolled nurses: why are they devalued? AB - Many nursing reports have made the assumption that enrolled nurses (ENs) lack the academic potential to complete RGN training. This has led to a very negative image that is damaging to the self-esteem of many ENs. Using an interactive approach, the author conducted a study of 11 ENs and found ambivalent attitudes existed toward their profession and identity. The implications of the ENB Higher Award for ENs is also discussed. PMID- 8217710 TI - Orthopaedics. Malnutrition: the key to pressure sores? AB - Elderly orthopaedic patients comprise a rapidly expanding population and suffer a high incidence of pressure sores compared to their younger counterparts. Malnutrition is one of the five most commonly cited risk factors for the development of pressure sores. This article briefly discusses the causes and effects of poor nutrition in elderly patients, and focuses on the importance of assessment of nutritional status in this group. Suggestions for the detection of malnutrition in elderly orthopaedic patients are made, with a view to reducing the incidence of pressure sores. PMID- 8217712 TI - Sleazy reading? PMID- 8217711 TI - Using continuous assessment in Oman. AB - The Sultanate of Oman is witnessing rapid advances in health care, and specifically nurse education. The Institute of Health Sciences has introduced a method of continuous assessment using a credit system adapted specially to fit the Institute's nursing programme. PMID- 8217713 TI - Computer reviews. Shareware share-alikes. PMID- 8217714 TI - Theatre nursing. Shaking hands with change. PMID- 8217715 TI - Theatre nursing. The labourer, the craftsman and the artist. PMID- 8217716 TI - Theatre nursing. Get DySSSy while you RUMBA. PMID- 8217717 TI - Don't give up on it: smoking cessation (continuing education credit). PMID- 8217718 TI - Working for awareness. PMID- 8217719 TI - Primary care. Practice nurses count: the new national census. PMID- 8217720 TI - A protocol for the detection of Chlamydia. AB - In spite of the fact that chlamydia can cause a variety of diseases affecting a variety of organs, health professionals and, in particular, the public seem to lack awareness of the difficulties the organism presents. The authors discuss how chlamydia affects humans, how it is diagnosed and treated, and then described the setting up of a multidisciplinary protocol that has assisted in the diagnosis of women attending gynaecology and genito-urinary medicine clinics. The protocol has resulted in many asymptomatic women being correctly diagnosed and treated, and the successful contact tracing of sexual partners. Multidisciplinary co operation, the authors suggest, is the secret behind the protocol's success. PMID- 8217721 TI - Preparation of nurse teachers: a rethink. PMID- 8217722 TI - Ward design: creating a healing patient-environment. AB - The drive for cost-effectiveness in hospital design over the decades has meant that minimal thought has been given to the effect of environments on patients' health. The author draws on research evidence to demonstrate how the appearance and ambience of patient areas can have profound effects on recovery patterns, and suggests that the creation of environments more conducive to healing need not incur heavy expense in time or money. PMID- 8217723 TI - Stroke registers: a way to improve care. AB - The authors describe their continued involvement in a research project to assess the incidence, case-fatality and management of stroke in three health authorities of Southern England. The article focuses on how the findings of their research have been used in two of the districts, and the role research can play in beginning to improve the services for people who have had strokes. PMID- 8217724 TI - Education: blackboard bungle. PMID- 8217726 TI - The Nat Health files. One NHS to go. PMID- 8217725 TI - The end is night. PMID- 8217727 TI - Community care: the strain of normality. PMID- 8217728 TI - Managing, but barely coping. PMID- 8217729 TI - Maternity: harsh labour 12 years on. PMID- 8217730 TI - Computer reviews: glowing references. PMID- 8217731 TI - [A year in Botswana]. PMID- 8217732 TI - [The premature and the sick newborn. 2. Transportation, risk factors, problems]. PMID- 8217733 TI - [Asphyxiating thoracic dysplasia (Jeune-syndrome)--a medical and nursing report]. PMID- 8217734 TI - [Poisonous and less poisonous plants. 10]. PMID- 8217735 TI - [Maturation of the organs of support and motion]. PMID- 8217736 TI - [Psychological stress in families with a chronically sick child]. PMID- 8217737 TI - [The calculation of treatment costs: what must be minded in families eligible for assistance]. PMID- 8217738 TI - [Hepatitis A--epidemiology and clinical picture]. PMID- 8217739 TI - [Report on children--request to nurses to contribute to the developmental diagnosis in infants]. PMID- 8217740 TI - Terminal complement complex in blood of patients with neurological diseases. AB - The local involvement of complement (C) in the pathophysiology of tissue lesions in several neurological diseases is known, but it has never been studied whether or not in neurological disorders the C activity in the circulation is altered as well. This was the aim of the present investigations. We measured in blood plasma, with an automatic device for analysis and quantitation of the haemolytic activity of the terminal complement complex, the variables T1, T2 and T3 which define the latter quantitatively. We did this, on the one hand, in 100 patients who had 46 neurological disorders systematized in 16 nosological groups, and, on the other hand, in a control group of 40 healthy blood-donors. The mean values of all variables found in the patients have not been statistically different from those found in the controls. This demonstrates that in neurological disorders possible activations of C remain restricted to the local tissue lesions and do not occur in blood, probably due to the opposition against C activation of the known inhibitor system. PMID- 8217741 TI - Carbohydrate metabolism, as reflected by glycosylated hemoglobin, in clinically active definite multiple sclerosis. AB - In 30 patients with the diagnosis of definite multiple sclerosis (MS) established on clinical criteria (CDMS-A1 patients), who were in a severe clinical state of MS, i.e., in whom one or more MS clinical signs or symptoms had become obvious during the last 10 days, the integrated concentration of plasma glucose over long term (the last 6-8 weeks) was established by measurement of the percent of the glycosylated fraction of hemoglobin (Hb A1). This was also investigated in two control groups: CG-1, which consisted in 33 registered healthy blood donors matched for sex and age with the MS patients, and CG-2, consisting in 7 patients with diabetic neuropathy. The mean-value of Hb A1 of 5.1% (SD = 0.82) in the MS patients and that of 5.12% (SD = 0.96) in CG-1 controls are not statistically different (t = 0.09). The Hb A1 mean-value of 10.53% (SD = 3.5) found in the CG-2 controls is different (p < 0.001) from both the mean-values in MS patients and CG 1 controls, which validates the reliability of the HB A1 investigation. The findings indicate that clinical activation in definite MS is not associated with disturbances of glucose metabolism. PMID- 8217742 TI - Predictors of the response to tricyclic antidepressants in major depression. AB - In a relatively young sample of 108 nonbipolar patients with major depressive disorder and at least moderately severe depression, the contribution of a comprehensive set of socio-demographic, psychosocial, clinical and personality trait variables toward the prediction of short-term, multidimensionally evaluated response to tricyclic antidepressants was investigated by univariate and multivariate analyses. There is a naturalistic study without a standard treatment protocol, but treatment type, duration and dosage were controlled. Only patients who received at least moderate dosages of tricyclic antidepressants for minimum four weeks were included in this study. A relatively low number of predictors emerged. Initial severity of both symptoms and impairment of functioning were the most powerful predictors for all outcome criteria. Illness history was also relevant. Personality traits reflecting vulnerable personality style at the emotional and interpersonal level proved their predictive value. The combination of independent variables by multivariate regression analyses improve the prediction of treatment response. PMID- 8217743 TI - Meniere's attacks associated with facial paralysis. AB - An 85-year-old man developed in the last 5 years three attacks on Meniere's syndrome associated with facial paralysis. The syndrome could be interpreted as a transient ischemic attack in the territory of the anterior inferior cerebellar artery. An alternative hypothesis could be to admit a Meniere's disease with compression of the facial nerve during the attacks of labyrinthine hydrops. PMID- 8217744 TI - Carotid endarterectomy. AB - Our study is based on 102 patients who underwent 104 carotid endarterectomies between 1980 and 1992. Sixty-three patients (61.8%) has surgery at left carotid artery bifurcation. 37 (36.2%) at right carotid artery bifurcation and in 2 cases (1.96%) the operation was performed at both carotid bifurcations. The patients' age ranged from 33 years to 73 years. The most frequently affected age group was between 41 and 50 years (47 cases). Postoperative death due to myocardial infarction occurred in one patient and other patient developed thrombosis of the internal carotid artery operated on. The remaining patients had a good surgical outcome. PMID- 8217745 TI - Communicative disorders in Wernicke's aphasics. AB - The purpose of this study was to analyze some aspects of communicative capacities in 25 predominantly Wernicke's aphasics. The patients with moderate and mild deficits were compared with severely affected patients. Answers in a standard interview were studied for two aspects: answer adequacy to question and conceptual thinking fluency. An initial examination was carried out in the first stage of aphasia and the second examination took place after 3 or 4 months since onset. Both parameters showed more important deficits in the group with severe disorders at onset. An improvement of communicative capacity was also noticed in both groups. The factors involved were discussed pointing out that wrong answers were not exclusively determined by a difficulty of auditory comprehension but by some deficits of conceptual thinking fluency or some other cognitive processes. PMID- 8217746 TI - The concentration of serum creatine-kinase in manic attacks of primary affective psychoses. AB - The study aims to observe whether subjects with a primary affective disease and manic attacks show modifications of serum concentration of creatine-kinase conferring it the role of a biologic marker. Serum concentration of creatine kinase was determined for 122 men with mono- and bipolar affective disease during the different stages as well as for schizophrenic men with different clinical forms excepting the affective form. The control group included 60 men. Data indicated that enzyme concentration can constitute a biological marker for a primary affective disease also showing the differences between the different stages of the disease (mania, hypomania, depression and the symptom-free intervals). PMID- 8217747 TI - Desmoplastic malignant melanoma: a clinicopathological study of 25 cases. AB - Sixteen cases of malignant melanoma which showed prominent desmoplastic and/or neurotropic features occurring throughout the tumour were compiled from the St John's Dermatology Centre histopathological archives. A further nine melanomas in which both conventional and desmoplastic melanoma were present concomitantly were also studied (three tumours with 66% desmoplastic change, two with 50%, and four with less than 50%). There were 14 males and 11 females, with a mean age of 64 years (range 39-86). The mean interval between presentation and diagnosis was 8 months. Eighteen of the 25 tumours were located on the head and neck, three were on the trunk, one was on the upper limb and three were on the lower limb. Histological review revealed 21 of 25 tumours with overlying atypical lentiginous hyperplasia, lentigo maligna melanoma, or superficial spreading malignant melanoma. Neurotropism was present in nine tumours, with the changes confined to local recurrences in two instances; neuroid differentiation was present in four tumours, and neural and perineural tumour spread was present in four tumours. The depth of invasion exceeded 6 mm in seven tumours, and was 2-6 mm in 16, and less than 2 mm in two. Eighteen of the 25 tumours were incompletely excised at the time of the first excision. Lymphoid aggregates were present in 16 tumours, but in most cases were limited to a few lymphoid foci. Melanin was identified in the dermal component of only five tumours, but not in areas showing typical histological features of desmoplastic malignant melanoma. Treatment was by surgical excision in all cases, and was preceded by radiotherapy in one case. Details of follow-up were obtained in all cases, and the duration ranged from 9 months to 10 years (mean, 3 years 11 months). Eleven patients had died; nine from melanoma and two from other causes. One patient was alive, with deep, inoperable local recurrence. Thirteen patients were alive and clinically free from tumour, including two patients in whom there had been local recurrence. A lower rate of neurotropism was present in the nine patients with partial desmoplastic change compared with those with desmoplasic change throughout the tumour, and represented the only significant difference between the two groups of patients. PMID- 8217748 TI - The quantification of free sphingosine in the stratum corneum of patients with hereditary ichthyosis. AB - Sphingosine is a long-chain base which provides the back-bone of all sphingolipid molecules. Free sphingosine is found in normal epidermis, especially in the stratum corneum. As a free molecule it may modify epidermal cell proliferation and differentiation through its inhibition of protein kinase C. Using a thin layer chromatography technique we have demonstrated in vitro that the erythrodermic ichthyoses show significantly lower levels of stratum corneum sphingosine than the non-erythrodermic types. The exact in vivo significance of this finding is unclear, but free sphingosine may have an important role in determining the inflammatory component of the hereditary ichthyoses. PMID- 8217749 TI - The vascular basement membrane in systemic sclerosis skin: heterogeneity of type IV collagen. AB - In systemic sclerosis (SS) changes in the dermal microvasculature include endothelial cell damage, a reduction in the number of vessels, and vascular basement membrane thickening. The basement membrane is a critical component of the vessel, and alterations in its structure may lead to changes in the surrounding tissue. In SS the altered basement membrane is associated with the subsequent development of fibrosis. To investigate the relationship between vascular basement membrane changes in affected skin and disease progression, immunohistochemical analyses were performed using both polyclonal and monoclonal antibodies against type IV collagen, the major basement membrane collagen. Using two monoclonal antibodies directed against different conformational epitopes within the (alpha 1)2 (alpha 2) helical domain, type IV collagen was detected in normal skin, and uninvolved SS skin, but not in later grades of disease. Identical results were obtained using a monoclonal antibody against a sequential determinant on the denatured alpha 1 (IV) chain. The use of a polyclonal antibody, however, showed that type IV collagen was present in all grades of disease, suggesting an alteration in the composition of type IV collagen with disease progression. PMID- 8217750 TI - An in vivo experimental model for effects of topical retinoic acid in human skin. AB - An occlusive patch-test assay has been developed for assessment of topical retinoid action in human epidermis. Previous work with this assay has demonstrated marked epidermal hyperplasia in skin treated with topical all-trans retinoic acid for 4 days and similar effects with the local irritant, sodium lauryl sulphate. To investigate the capabilities of this assay further, a time course and dose-response were performed with all-trans-retinoic acid, and a comparison made with sodium lauryl sulphate. At no time, between 1 and 4 days, could the clinical or histological effects of 0.1% and 0.025% cream formulations of all-trans-retinoic acid be distinguished from each other. Epidermal hyperplasia was used to generate a 4-day dose-response for all-trans-retinoic acid at concentrations from 0.001 to 0.025% dissolved in a 70% ethanol/30% propylene glycol vehicle. All-trans-retinoic acid could be successfully differentiated from sodium lauryl sulphate at 2 days by virtue of its greater ability to increase epidermal thickness, spongiosis and glycosaminoglycan deposition. It appears that although all-trans-retinoic acid and sodium lauryl sulphate produce similar epidermal histological changes at 4 days, significant differences at earlier time-points suggest differing mechanisms of action. In addition, this in vivo human assay is able to provide potency ranking for doses of all-trans-retinoic acid, and may predict clinical efficacy of retinoids in improvement of acne and/or photodamage. PMID- 8217751 TI - The effects of retinoids and terbinafine on the human hepatic microsomal metabolism of cyclosporin. AB - Following the observation of increased trough whole blood cyclosporin A (CyA) concentrations and reduced renal function in a patient with recalcitrant generalized pustular psoriasis treated with a combination of CyA and etretinate, the effect of vitamin A analogues on human microsomal cytochrome P450-dependent CyA metabolism was investigated in vitro. In addition, the effect of terbinafine, a new allylamine antifungal agent, was also tested. Etretinate, its major metabolite acitretin, and isotretinoin, each at a single concentration of 100 microM, inhibited total hepatic microsomal CyA metabolism to a similar extent (33 45%, compared with control values). The generation of total primary and total secondary CyA metabolites was also inhibited to a similar extent by each of the retinoids. Conversely, terbinafine was without significant effect on CyA metabolism in vitro. The results, which suggest that inhibition of hepatic CyA metabolism by retinoids may contribute to increased circulating CyA concentrations, are discussed in relation to other potential drug interactions, and to the use of etretinate in reducing the CyA administered dose. PMID- 8217752 TI - Follicular concentrations of azelaic acid after a single topical application. AB - Follicular concentrations of azelaic acid (AzA) were determined in vivo using a rapid, non-invasive method, after a single topical application of 20% (w/w) AzA cream, in order to establish whether the in vitro antimicrobial effects observed in previous studies are relevant in vivo. Preweighed amounts of 20% (w/w) AzA cream were applied over demarcated areas on the forehead and back of nine young adults, and samples were taken over a period of 5 h. AzA was removed from the skin surface by washing with acetone, and follicular casts were collected using cyanacrylate gel. The samples were centrifuged to remove particulate matter, and the supernatants derivatized for analysis by HPLC. Although the results showed wide-ranging variability, the follicular concentration increased as the amount present on the surface declined. The maximum follicular concentrations of AzA attained ranged from 7.5 to 52.5 ng (micrograms of follicular casts)-1 and 0.5 to 23.4 ng (micrograms of follicular casts)-1 in samples taken from the back and forehead, respectively. Assuming an average density of follicular material of 0.9 g ml-1, the mean maximum follicular concentration attained on the back was between 36 and 251 mmol/l, and on the forehead was between 2 and 112 mmol/l, and indicates that the concentration of AzA attained in follicular casts after a single topical application is comparable with the concentration required to inhibit the growth of Propionibacterium acnes and Staphylococcus epidermidis, in vitro. PMID- 8217753 TI - Characterization of pigmented granules in minocycline-induced cutaneous pigmentation: observations using fluorescence microscopy and high-performance liquid chromatography. AB - We describe a technique to facilitate histopathological detection and quantitative measurement of trace amounts of tissue minocycline. In a patient with minocycline-induced hyperpigmentation, a series of biopsies were taken from the affected skin over a period of 54 months, and examined for tissue minocycline deposition. Frozen sections treated with 1 M MgCl2-ethanol yielded minocycline specific yellowish fluorescence, the location of which corresponded to clumps of granular deposits in the dermis. A decrease in the number of fluorescent granules correlated with the clinical resolution of hyperpigmentation and a significant decrease in the tissue minocycline level. Our data also provide further support for the concept that the pigment granules contain insoluble complexes of minocycline chelated with iron. The fluorescence technique is simple, sensitive, and reproducible. PMID- 8217754 TI - Difference in clinical features and HLA antigens between familial and non familial vitiligo of non-segmental type. AB - Of 131 patients with non-segmental vitiligo studied, 29 (22%) had a family history of this disorder. The clinical features and HLA antigens were assessed, and a comparison made between patients with familial and those with non-familial, non-segmental vitiligo. Familial patients developed skin lesions significantly earlier than non-familial patients. There was a significant association between HLA-B46 and familial non-segmental vitiligo, whereas HLA-A31 and CW4 were found in non-familial patients. The differences in clinical features and HLA phenotypes suggest heterogeneity in the pathogenic process between familial and non-familial vitiligo patients. PMID- 8217755 TI - Urine calcium excretion during treatment of psoriasis with topical calcipotriol. AB - Urine calcium excretion is a very sensitive method of detecting vitamin D intoxication, and may rise in the absence of any apparent change in the serum level. Little attention has been paid to urine calcium levels during the large trials performed to assess the efficacy and safety of calcipotriol in psoriasis vulgaris. There are some urine calcium data from short-term studies of average dose rates of calcipotriol. However, there are no published data on long-term usage, nor on the use of dose rates at the upper end of the licensed range (100 g/week). In a group of 20 patients, who were using typical quantities of calcipotriol ointment (50 micrograms/g) to treat psoriasis vulgaris, urine calcium excretion was measured prior to treatment, and then monthly for 12 months. There was no significant change in urine calcium over the year. In a separate group of 10 patients, who were using calcipotriol in the same concentration, at the maximum recommended rate of 100 g/week, urine calcium was measured at baseline, and after 2 and 4 weeks. There was a statistically significant rise in calcium excretion. This is the first trial to demonstrate that topical calcipotriol affects calcium homeostasis when used within the recommended dose range. Further studies are necessary to determine more precisely the magnitude and variability of this effect in a large group of individuals. For the present, caution is required when prescribing calcipotriol for any patient with known hypercalciuria or a history of renal stone formation. Consideration should be given to monitoring urine calcium excretion during prolonged use at dose rates approaching the recommended maximum. PMID- 8217756 TI - Topical tretinoin (retinoic acid) improves melasma. A vehicle-controlled, clinical trial. AB - Melasma is a common disorder of cutaneous hyperpigmentation predominantly affecting the faces of women. Little is known about the aetiology of melasma, and treatment is frequently disappointing. Topical tretinoin is of benefit in treating other forms of hyperpigmentation, for example liver spots, and we therefore investigated its effectiveness in melasma. Thirty-eight women completed a randomized, vehicle-controlled study, in which they applied 0.1% tretinoin (n = 19) or vehicle cream (n = 19) once daily to the face for 40 weeks. At the end of treatment 13 (68%) of 19 tretinoin-treated patients were clinically rated as improved or much improved, compared with 1 (5%) of 19 in the vehicle group (P = 0.0006). Significant improvement first occurred after 24 weeks of tretinoin treatment. Colorimetry (an objective measure of skin colour) demonstrated a 0.9 unit lightening of tretinoin-treated melasma and a 0.3 unit darkening with vehicle (P = 0.01); these results correlated with clinical lightening (r = 0.55, P = 0.0005). Histologically, epidermal pigment was reduced 36% following tretinoin treatment, compared with a 50% increase with vehicle (P = 0.002). Reduction in epidermal pigment also correlated with clinical lightening (r = 0.41, P = 0.01). Moderate cutaneous side-effects of erythema and desquamation occurred in 88% of tretinoin-treated and 29% of vehicle-treated patients. Topical 0.1% tretinoin produces significant clinical improvement of melasma, mainly due to reduction in epidermal pigment, but improvement is slow. PMID- 8217757 TI - Cyclosporin greatly improves the quality of life of adults with severe atopic dermatitis. A randomized, double-blind, placebo-controlled trial. AB - A multicentre, randomized, double-blind, controlled crossover clinical trial was conducted on 33 patients with severe refractory atopic dermatitis, to determine the effects of cyclosporin (5 mg/kg/day) on their health-related quality of life. Treatments were administered for 8-week periods. One group (n = 16) received placebo followed by cyclosporin, and the other (n = 17) received cyclosporin and then placebo. Health-related quality of life was assessed at 0, 8 and 16 weeks using a general measure, the United Kingdom Sickness Impact Profile (UKSIP), an eczema-specific measure, the Eczema Disability Index (EDI), and a global 5-point rating scale of overall health (very good to very poor). In addition, clinical assessments (i.e. extent and activity of disease) were made by the investigators. UKSIP and EDI scores indicated significant improvement in quality of life (P < 0.05-P < 0.01) of patients with atopic dermatitis after treatment with cyclosporin. Although no patient required withdrawal from the study, 20 patients receiving cyclosporin reported adverse events, compared with eight taking placebo. There was a close correlation (P < 0.05-P < 0.01) between the UKSIP and EDI scores. In contrast, there was either no correlation, or only a very poor correlation, between the quality of life parameters and clinical measures of extent and activity of eczema. When cyclosporin was stopped, relapse was rapid, but the mean scores for disease activity and extent of disease were less than their baseline values (i.e. an improvement of greater than 25% was maintained in 11 patients at week 4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217758 TI - Oral psoralen photochemotherapy in severe childhood atopic eczema: an update. AB - Over a 6-year period, oral psoralen photochemotherapy (oral PUVA) has been used to treat 53 children (mean age 11.2 years) with severe atopic eczema unresponsive to other therapy. Twice-weekly treatment resulted in clearance or near-clearance of disease in 39 (74%) after a mean of 9 weeks. Thirty-two (82%) of these 39 children were subsequently able to achieve remission of disease following gradual withdrawal of treatment; the mean duration of treatment to remission was 37 weeks; the mean cumulative UVA dose was 1118J/cm2, and the mean number of treatments was 59. Twenty-two remain in remission a year after discontinuing treatment. Short- and medium-term adverse effects, other than occasional intolerance of treatment, have not been prominent. Despite anxieties about possible long-term hazards, it is our view that oral PUVA is justified in a small proportion of older children with disabling atopic eczema. We believe that it has substantial advantages over other therapeutic options in selected cases, particularly in providing improved growth and an opportunity for sustained remission. PMID- 8217759 TI - Does naftifine have anti-inflammatory properties? A double-blind comparative study with 1% clotrimazole/1% hydrocortisone in clinically diagnosed fungal infection of the skin. AB - In a multicentre, double-blind, randomized, parallel group study in general practice, 269 patients with clinically diagnosed fungal infection of the skin were treated with either naftifine (Exoderil) or 1% clotrimazole plus 1% hydrocortisone (CHC; Canesten HC) applied twice daily for 4 weeks. Only 115 patients were shown subsequently to have a fungal infection by laboratory tests; the others had inflammatory disease of unknown aetiology. In those with fungal disease, both treatments were equally effective in terms of mycological cure (negative microscopy and culture). Clinical results for all 265 patients showed no clinically identifiable difference between the two preparations in terms of resolution of the disease, indicating that naftifine does have anti-inflammatory activity at least equal to CHC. This study suggests that there is no clinical advantage in treating patients with clinically diagnosed fungal infection of the skin with an antimycotic/corticosteroid combination as opposed to naftifine alone. PMID- 8217760 TI - Linear prurigo simulating dermatitis artefacta in dominant dystrophic epidermolysis bullosa. AB - We report a family suffering from dominant dystrophic epidermolysis bullosa, in whom linear lichenified lesions and troublesome pruritus were prominent features. We consider that this clinical picture may constitute a separate subtype of this disorder. PMID- 8217761 TI - Hidradenitis suppurativa as a presenting feature of premature adrenarche. AB - We report a girl with premature adrenarche, in whom the presenting feature was hidradenitis suppurativa. This association lends support to the view that hidradenitis suppurativa is an androgen-dependent disorder. PMID- 8217762 TI - Solitary congenital self-healing reticulohistiocytosis. AB - Congenital self-healing reticulohistiocytosis (CSHR) was first described in 1973 by Hashimoto and Pritzker. Since then, both multiple and solitary forms have been described. We report a further case of solitary congenital self-healing reticulohistiocytosis. CSHR is a rare disorder which frequently presents a diagnostic dilemma in the newborn. Nodular forms of systemic Langerhans cell histiocytosis may present in a manner similar to CSHR. Because their differentiation on histopathological grounds is impossible, physical examination, laboratory investigations, and follow-up are necessary to ensure a lack of systemic involvement. Although previously thought to represent a rare variant of CSHR, solitary lesions of CSHR account for almost 25% of reported cases. A review of the literature relating to solitary CSHR, and a consideration of the differential diagnosis of a solitary congenital nodule, are also presented. PMID- 8217764 TI - Pemphigus associated with nail dystrophy. AB - Two patients suffering from pemphigus vulgaris were found to have nail dystrophies which antedated the onset of mucocutaneous lesions by many years. The nail changes improved substantially on treatment of the bullous disease. One patient had nail matrix histology consistent with pemphigus, and both had positive direct immunofluorescence with intercellular IgG in the matrix epithelium, as well as at other body sites. We propose that dystrophic nails, as a non-specific indicator of autoimmune disease, are a genuine and relevant finding in pemphigus. PMID- 8217763 TI - Cyclical psoriatic arthritis responding to anti-oestrogen therapy. AB - We report a patient with severe psoriatic arthritis in whom the severity of both the arthritis and psoriasis fluctuated with the menstrual cycle. These features failed to improve with standard therapy, but there was a prompt response to treatment which suppressed oestrogen secretion. Such treatment should be considered in patients with disabling cyclical changes in psoriatic arthritis. PMID- 8217765 TI - Extramedullary plasmacytoma: cytological and genotypic studies. AB - A 62-year-old woman had multiple plasmacytomas in the skin and lymph nodes, without Bence-Jones protein or a monoclonal peak of serum immunoglobulins. Infiltrating plasmacytoid cells expressed cytoplasmic IgG (lambda) and surface CD38, without any B-cell markers. There was no visceral or bone marrow involvement suggestive of multiple myeloma. Southern blot analysis of extracted DNA from the cutaneous lesions showed two rearranged bands with an immunoglobulin, but not a T-cell receptor, gene probe. The patient showed a poor response to chemotherapy, and died of bronchopneumonia. The clinical course and cytological features differentiate multiple cutaneous extramedullary plasmacytomas from solitary cutaneous extramedullary plasmacytoma and cutaneous lesions associated with multiple myeloma. PMID- 8217766 TI - Serious childhood angiomas: unsuccessful alpha-2b interferon treatment. A report of four cases. AB - Over a 4-year period, we managed four children with alarming haemangiomas (two cases of Kasabach-Merritt syndrome and two life-threatening haemangiomas). Systemic steroid therapy was ineffective. Other treatments (radiotherapy, anti platelet drugs) were also ineffective in the Kasabach-Merritt patients. On the basis of recent reports on the effects of interferon on endothelial cells, we used alpha-2 interferon therapy, but obtained no response. PMID- 8217767 TI - Urine neopterin concentrations and activity of psoriasis. PMID- 8217768 TI - An acantholytic bullous eruption after norfloxacin. PMID- 8217769 TI - Itraconazole-induced acute hepatitis. PMID- 8217770 TI - Acquired zinc deficiency presenting with an acutely tender erythematous scrotum. PMID- 8217771 TI - Unilateral bullous pemphigoid in a hemiplegic patient. PMID- 8217772 TI - Opportunistic cutaneous myiasis following radiotherapy for squamous cell carcinoma of the left temple. PMID- 8217773 TI - Rapid clearing of kerion ringworm with terbinafine. PMID- 8217774 TI - PUVA-induced skin pain. PMID- 8217775 TI - Transcription factors: an overview. PMID- 8217776 TI - Transcription:factors, regulation and differentiation. Keystone Symposium on Molecular Biology (1993). PMID- 8217777 TI - The effect of platelet inhibitory therapy on graft thromboresistance. AB - Greyhounds (n = 38) were randomized to aspirin and dipyridamole (ASA + DPM), the thromboxane synthetase inhibitor (TSI) CGS12970 (CIBA-GEIGY) or placebo twice daily for 48 hours prior to bilateral implantation of femoral artery Dacron grafts. In-vivo 111In-platelet deposition on grafts was measured at 5 days and 2 months. Grafts were removed at 2 months when ex-vivo graft and arterial release of 6-ketoprostaglandin F1a (6-keto PGF1a) was measured by radioimmunoassay. Graft 6-keto-PGF1a was significantly increased by CGS12970 but ASA + DPM had no significant effect. ASA + DPM significantly reduced arterial 6-keto-PGF1a although this was marginally increased by CGS12970. Neither active treatment reduced in-vivo 111In-platelet deposition. Preservation of vascular or graft prostacyclin by thromboxane synthetase inhibitors may represent an alternative strategy in preventing prosthetic graft thrombosis. PMID- 8217778 TI - Lactoferrin regulates the release of tumour necrosis factor alpha and interleukin 6 in vivo. AB - The effects of bovine lactoferrin on the serum cytokine levels, induced by lipopolysaccharide (LPS) in mice, are described. Bovine lactoferrin (BLF) introduced intravenously, 24 hours before i.v. injection of 50 micrograms of LPS, significantly lowered the serum concentration of TNF-alpha. Doses of BLF lower than 100 micrograms as well as pretreatment of mice with BLF on days 6-2 or 12-2 hours before LPS challenge, were not effective. Moreover, BLF induces by itself a relatively high level of IL-6, peaking at 1 hour following injection. Pretreatment of LPS-injected mice with BLF causes, in addition, a small but statistically significant drop in IL-6 level. Human albumin, used as a control protein, did not cause any changes in the cytokine levels. The data reported herein provide a satisfactory explanation with regard to preventive activity of LF in infection. PMID- 8217779 TI - Evidence for the experimental transmission of cerebral beta-amyloidosis to primates. AB - The brains of three marmosets (Callithrix jacchus) injected intracerebrally 6-7 years earlier with brain tissue from a patient with early onset Alzheimer's disease were found to contain moderate numbers of amyloid plaques with associated argyrophilic dystrophic neurites and cerebral amyloid angiopathy but no neurofibrillary tangles. The plaques and vascular amyloid stained positively with antibodies to beta (A4)-protein. The brains of three age-matched control marmosets from the same colony did not show these neuropathological features. The brain of one of two marmosets injected with brain tissue from a patient with prion disease with concomitant beta-amyloid plaques and cerebral amyloid angiopathy also showed beta-amyloid plaques and angiopathy but no spongiform encephalopathy. An occasional plaque was found in the brains of two of four marmosets injected with brain tissue from three elderly patients with age-related pathology, two of whom had an additional diagnosis of possible prion disease. Neither plaques nor cerebral amyloid angiopathy were found in six other marmosets who were older than the injected animals, in 12 further marmosets who were slightly younger but who had been injected several years previously with brain tissue which did not contain beta-amyloid, or in 10 younger marmosets who had been subjected to various neurosurgical procedures. These results suggest that cerebral beta-amyloidosis may be induced by the introduction of exogenous amyloid beta-protein. PMID- 8217780 TI - Depression of chemiluminescence during dengue virus infection of mice: role of cytokines. AB - The effect of dengue type 2 virus (DV) and the cytokines induced by it, on the chemiluminescence (CL) response of mouse spleen cells was studied by luminol dependent CL. Following intracerebral (i.c.) inoculation of DV, an initial increase in CL response was observed which was followed by a sharp decline from the 4th day post-infection with lowest values on days 5 and 6. DV-induced depression of CL was inhibited by pretreatment of mice with antisera against the two DV-induced cytokines, the cytotoxic factor (CF) and the cytotoxin (CF2), but antisera against the other two helper (HF) or suppressor (SF) cytokines had minimal effect. Inoculation of CF or CF2 into mice depressed the CL in dose dependent manner at 2 hours but increased it at the 3rd day. Inoculation of HF or SF had no significant effect. Treatment of mice with the cytokines in presence of the specific antisera had an enhancing effect on the CL response. The antisera alone had no effect on CL. Thus, these findings indicate that DV infection impaired the generation of respiratory burst, and the impairment appeared to be mediated by two DV-induced cytokines (CF/CF2). Targetting of the cytokines to M phi was significantly enhanced in the presence of specific anti-cytokine antibodies. PMID- 8217781 TI - Zinc supplementation in experimental liver cirrhosis: a morphological, structural and ultrastructural study. AB - Zinc treatment in liver cirrhosis is known to prevent a number of clinical symptoms. Previous studies have also indicated that Zn has a protective effect on the development of the clinical, biochemical and morphological manifestations of hepatic injury if administered simultaneously with the noxious agent. In this study, the protective effects of zinc treatment against the development of liver cirrhosis have been tested in cirrhotic rats treated by intragastric administration of CCl4. The development of morphological lesions has been investigated by means of standardized and comparable techniques, LM, TEM, SEM, microvascular casts and measurements of liver collagen content by colorimetric determination in paraffin embedded sections. LM and EM observations showed typical morphological features of cirrhosis in all CCl4 treated rats. In the same group of animals, the microvascular casts showed the development of the typical 'perinodular' branching and the various anastomoses of pre and post-sinusoidal vessels. Colorimetric evaluation has shown a significant increase in collagen content after CCl4 treatment. Qualitative and quantitative data of livers of CCl4 treated rats supplemented or not with zinc were significantly similar. In conclusion, zinc treatment influences biochemical parameters, but not the morphology of liver cirrhosis. PMID- 8217782 TI - The immunocytochemical localization of tumour necrosis factor and leukotriene in the rat kidney after treatment with lipopolysaccharide. AB - Abundant inflammatory cells such as polymorphonuclear leucocytes and macrophages accumulated and adhered to the endothelial surface of glomerular and intertubular veins and capillaries in rat kidneys after administration of bacterial lipopolysaccharide (LPS). There was also damage to both endothelial cells and proximal tubular cells, including intracytoplasmic oedema, and an increase in the number of lysosomes in the proximal tubular cells in the LPS-treated samples. Immunocytochemistry was used to demonstrate tumour necrosis factor (TNF) and leukotriene (LTR) in both LPS-treated and control samples. Immunoreactive LTR seen in the lysosomes of inflammatory cells attached to the endothelial cell surface may indicate the onset of endothelial cell damage. Positive immunoreactive TNF and LTR were seen on the endothelial cell surface only in the LPS-treated samples, indicating that TNF and LTR may enhance the adhesion of leucocytes to endothelium. Positive reactions of TNF and LTR in lysosomes of the mesangial cells suggest that lysosomes of such cells may be involved in the synthesis and storage of TNF and LTR. In addition to these reaction sites, lysosomes of proximal tubular cells were immunoreactive for LTR. These endogenous LTRs may be implicated in the degeneration of the proximal tubular cells. PMID- 8217783 TI - Leishmania (Viannia) panamensis-induced cutaneous leishmaniasis in Balb/c mice: pathology. AB - Leishmania (Viannia) panamensis infected Balb/c mice developed a progressive swelling in the injected footpad that grew to a tumour-like lesion from day 80 onwards. We did not observe any typical ulcera, necrosis or metastasis to other parts of the skin. Neither did we observe any histopathological changes in liver or spleen during the experiment. At the site of injection, we observed progressive changes ranging from a moderate, mixed inflammatory infiltrate with few leishmania amastigotes in the macrophages to an extensive inflammation composed of monomorphic vacuolated macrophages containing large numbers of parasites. A granulomatous pattern with presence of epithelioid cells and a few multinucleated giant cells was observed at the initial phase of the infection. During later stages, focal necrosis with polymorphonuclear neutrophils was seen. Lymph nodes presented granulomatous lesions in the subcapsular area, numerous plasma cells in the medullary cords and macrophages with leishmania organisms in dilated cortical sinuses at the 4th and the 6th months of infection. This Leishmania (Viannia) panamensis infected Balb/c mice seems to be a good model for continued studies of the pathogenesis of cutaneous leishmaniasis and also for drug trials in the development of new therapeutic tools. PMID- 8217784 TI - Biphasic disease of central nervous system induced in DBA/2 mice by the D variant of encephalomyocarditis virus (EMC-D). AB - DBA/2 mice infected with the D variant of encephalomyocarditis virus (EMC-D) (10(1) PFU/head) developed biphasic hind limb paralysis. At 12 days post inoculation (12 DPI), 60% of the infected mice developed hind limb paralysis and two-thirds of them showed recovery by 33 DPI. Thereafter, about 30% of the mice which once showed paralysis developed hind limb paralysis again by 56 DPI. Histopathologically, the spinal cord lesion of paralysed mice was characterized by demyelination associated with infiltration of macrophages in the funiculus lateralis and by degeneration of neurons in the cornu ventrale. Virus antigens were detected in the cytoplasm of degenerated neurons and oligodendrocytes in the demyelinated lesions from 3 to 14 DPI. At 28 DPI, demyelinated lesions reduced in size due to prominent remyelination. At 56 DPI, infiltration of mononuclear cells mainly composed of anti-L3T4-positive (CD4+) T cells were observed in the cornu ventrale of the mice showing recurrence of hind limb paralysis. These results suggested that the early paralysis was mainly due to demyelination in funiculus lateralis caused by EMC-D and macrophages and that the late paralysis was due to degeneration of motor neurons, probably brought about by CD4+ T cells. PMID- 8217785 TI - The induction of mitochondrial myopathy in the rat by feeding beta guanidinopropionic acid and the reversibility of the induced mitochondrial lesions: a biochemical and ultrastructural investigation. AB - The long-lasting depletions of creatine phosphate induced by feeding rats with a beta-guanidinopropionic acid (GPA)-supplemented diet induces specific mitochondrial alterations in skeletal muscles very similar to those observed in human mitochondrial myopathies. The slow-twitch soleus muscle appears to be affected primarily, while the fast-twitch extensor digitorum longus is affected less severely and only after a longer period of treatment (6 months). Changes in the enzyme activities of glucose metabolism appear to be secondary and differ between the two muscles. Withdrawal of GPA from the diet after 2 months of treatment shows that both mitochondrial alterations and biochemical modification are reversible. PMID- 8217787 TI - Bone marrow transplantation for myelodysplastic syndrome and secondary leukaemias. PMID- 8217786 TI - Platelet factors induce chemotactic migration of murine mammary adenocarcinoma cells with different metastatic capabilities. AB - The chemotactic response of neoplastic cells (NC) induced by soluble platelet factors was investigated. NC suspensions isolated from murine mammary gland adenocarcinomas having different metastatic capabilities were incubated in Boyden's chambers and challenged with (1) 'Early Platelet Factors' (EP), obtained from the soluble fraction of recently collagen-activated human platelets, and (2) 'Late Platelet Factors' (LP), isolated after 24 hours incubation of the platelet aggregates. Chemotaxis was expressed as the distance travelled by NC through nitrocellulose filters. NC isolated from M3, the tumour line having the stronger metastatic potential, showed a significant chemotactic response towards LP factors, whereas NC from the M2 line exhibiting the lower metastatic behaviour, showed a chemotactic response towards EP factors. Both tumour cell lines lacked motion capability towards the well known chemoattractant peptide N-f-Met-Leu-Phe Phe as well as to serum, plasma, collagen type I or culture medium. The different chemotactic response of both tumour lines when they were challenged by concentration gradients of factors released by early or late collagen-activated human platelets, confirm a relationship between platelet activity and metastatic capabilities and suggests that platelet chemoattractants might play a role in the metastatic dissemination of these mammary gland adenocarcinomas. PMID- 8217788 TI - Chronic administration of transforming growth factor-beta suppresses erythropoietin-dependent erythropoiesis and induces tumour necrosis factor in vivo. AB - Transforming growth factor beta is a known inhibitor of the proliferation and differentiation of early haematopoietic progenitors but has no effect on mature erythroid cells in vitro. Mice injected with rhTGF beta 1 exhibited severe and progressive suppression of erythropoiesis manifested by a decline of reticulocyte count, marrow erythroblasts and marrow and spleen CFU-E, which could be prevented by administration of erythropoietin. This suppression of erythropoiesis was associated with the appearance of tumour necrosis factor in the blood, development of pronounced cachexia and depression of serum erythropoietin levels. TGF beta induces TNF in vivo that leads to cachexia, decrease of serum erythropoietin levels and suppression of erythropoietin dependent erythropoiesis. PMID- 8217789 TI - Increased serum levels of transforming growth factor beta-1 in patients affected by thrombotic thrombocytopenic purpura (TTP): its implications on bone marrow haematopoiesis. AB - In this study we evaluated the effect of serum collected from seven thrombotic thrombocytopenic purpura (TTP) patients, either in the acute phase of the disease or in clinical remission, on the in vitro growth of bone marrow haematopoietic progenitor cells, obtained from the same TTP patients in clinical remission and from normal donors. The addition to the cultures of autologous sera collected from TTP patients in acute phase of the disease showed a clear-cut dose-dependent inhibition of immature haematopoietic progenitor cells (BFU-E, CFU-meg and 14th day CFU-GM). On the other hand, no inhibitory effects were observed on more mature 7th day CFU-GM. Interestingly, also sera collected from TTP patients in clinical remission still maintained some inhibitory activity on the growth of immature progenitor cells. A similar inhibitory activity was noticed when TTP sera were tested on normal bone marrow haematopoietic progenitor cells. Such inhibitory activity was significantly reduced in blocking experiments by the addition of a polyclonal neutralizing anti-TGF-beta 1 antibody and the presence of increased levels of both bioactive and latent TGF-beta 1 in TTP sera was confirmed in a bioassay on CCL64 cells. These data contribute to explain the lack of a clear compensatory haematopoiesis observed in some patients with active TTP and add further evidence to the notion of the existence of a state of latent platelet activation in TTP patients in clinical remission. PMID- 8217790 TI - The resistance of macrophage-like tumour cell lines to growth inhibition by lipopolysaccharide and pertussis toxin. AB - The process of tumorigenesis is frequently associated with resistance to growth inhibition by physiological regulators of normal cells. Murine macrophage-like cell lines BAC1.2F5, RAW264, J774.1A and PU5/1.8 were resistant to growth inhibition by bacterial lipopolysaccharide (LPS) and pertussis toxin, agents that blocked growth of primary bone marrow-derived macrophages (BMDM) in the presence of macrophage colony-stimulating factor (CSF-1). The resistance of the CSF-1 dependent cell line BAC1.2F5 to growth inhibition by pertussis toxin argues against the possibility that pertussis toxin-sensitive G proteins are essential for the pathway of growth stimulation by CSF-1. Conversely, these data add further weight to the argument that LPS mediates some of its biological activities by mimicking the action of pertussis toxin and inhibiting G protein function. The resistance of cell lines to LPS and pertussis toxin was not correlated with any alteration in the expression of mRNA encoding any of three pertussis-toxin sensitive G protein alpha subunits. The pattern of G protein expression was consistent between primary cells and tumour cells, suggesting that this is a differentiation marker. In particular, Gi alpha 2 mRNA was expressed at remarkably high levels in all of the cells. The specificity of LPS resistance was investigated by studying down-regulation of CSF-1 binding and induction of protooncogene c-fos and tumour necrosis factor (TNF) mRNA. BAC1.2F5 cells were LPS-resistant in each of these assays. In CSF-1 binding, RAW264 and J774.1A responded in the same way as bone marrow-derived macrophages but required higher doses of LPS, whereas c-fos and TNF mRNA were induced in these cells at concentrations that did not inhibit growth. In PU5/1.8 cells, CSF-1 binding was already very low and was not further down-regulated, but c-fos and TNF mRNA was inducible by LPS. By contrast to primary macrophages, the cell lines did not respond to LPS with down-regulation of c-fms mRNA, which encodes the CSF-1 receptor. Hence, the resistance of macrophage-like tumour cells to LPS and pertussis toxin was specific to the pathways controlling growth, and was correlated with altered regulation of the CSF-1 receptor. PMID- 8217791 TI - Role in growth regulation of cytokines and cytokine receptors in acute lymphoblastic leukaemia expressing myeloid markers. AB - The biological roles of cytokines and cytokine receptors were examined in acute lymphoblastic leukaemia cells expressing myeloid antigens (My+ ALL). Interleukin 3 (IL-3), granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), and low molecular-weight B-cell growth factor (LW-BCGF) could induce DNA synthesis in certain cases of My+ ALL. Whereas in My- ALL the stimulatory effects were shown only with LW-BCGF. Acute myelogenous leukaemia (AML) cells were activated with multiple cytokines including interleukin-1 (IL 1), IL-3, G-CSF and GM-CSF. Specific receptors for IL-1 and IL-3 were strongly expressed on both My+ and My- ALL cells. These receptors, however, were weakly detectable on AML cells. Additionally we studied the production of tumour necrosis factor-alpha and IL-1 by leukaemic blasts and found that distinct amounts of both cytokines were released from My+ ALL cells and AML cells, but not from My- ALL cells. The profiles of cytokines and cytokine receptors expressed by My+ ALL showed both similarities and differences to those in My- ALL or AML. The proliferation of My+ ALL cells was dependent on multiple cytokines that would regulate growth and maturation in a lineage-restricted fashion. These data suggested that My+ ALL cells might originate from uncommitted haematopoietic precursor cells coexpressing features of both lymphoid and myeloid lineages. PMID- 8217792 TI - Differential expression of terminal transferase (TdT) in acute lymphocytic leukaemia expressing myeloid antigens and TdT positive acute myeloid leukaemia as compared to myeloid antigen negative acute lymphocytic leukaemia. AB - We examined whether the allegedly aberrant expression of the lymphoid lineage associated DNA polymerase, terminal deoxynucleotidyl transferase (TdT), in acute myeloid leukaemia (AML) is associated with alterations of the enzyme at the cellular, biochemical or transcriptional level when compared to lymphoid leukaemia (ALL), either lacking or expressing myeloid antigens. By flowcytometric analysis, the intensity of TdT staining with monoclonal anti-TdT antibody was considerably weaker in TdT+ AML and myeloid+ ALL (M+ ALL) than in myeloid- ALL (M ALL). TdT enzyme activity in TdT+ AML was on an average 10%, and in M+ ALL 25% of that measured in M- ALL. Anti-TdT antibodies precipitated a major specific protein of identical relative molecular mass (58 kD) from metabolically labelled TdT+ myeloblasts and lymphoblasts. By Northern blot analysis and ribonuclease protection assay, TdT transcript levels were significantly lower in TdT+ myeloblasts and M+ lymphoblasts than in M- ALL (P < 0.0001). The level of TdT transcription in AML was independent of the simultaneous expression of lymphoid specific antigens, such as CD2 and CD19. Our data demonstrate that TdT expression is downregulated in association with myeloid features, not only in AML but also in ALL. This observation may provide the molecular basis for the differential therapeutic responsiveness, particularly to glucocorticoids, in these various leukaemia subtypes. PMID- 8217793 TI - Effect of transfer factor on myelosuppression and related morbidity induced by chemotherapy in acute leukaemias. AB - The aim of this study is to determine the safety and efficacy of Transfer Factor (TF) in accelerating the haematopoietic recovery in patients with acute leukaemias (AL), following intensive therapy to induce remission of the disease. Twenty-two patients with different types of AL (16 AML, three BC-CML and three ALL) were studied. The patients were divided in two groups. Group 1 (eight AML, two BC-CML and one ALL) received, after myelosuppression induced by chemotherapy, TF (1 unit daily, subcutaneous) until leucocyte count was > 2.5 x 10(9)/l and platelet count > 80 x 10(9)/l. Group 2 was considered the control group and did not receive TF. Treatment with TF accelerated the recovery of neutrophils, leucocytes, platelets (P < 0.001) and haemoglobin (P < 0.01). As a logical consequence, incidence and severity of infection and haemorrhage were lesser in the TF group than in the control group. There was no evidence that TF accelerated the re-growth of leukaemic cells. It seems that TF is safe in AL, accelerating haematopoietic recovery. However, it should be used with caution until results of additional trials become available. PMID- 8217794 TI - Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia. AB - Chronic lymphocytic leukaemia (CLL) is known to be a stable monoclonal neoplasm. In contrast to early studies demonstrating no more than two hybridizing immunoglobulin heavy chain bands corresponding to the two expected alleles, we have demonstrated an unexpected multiband pattern when the HindIII-digested DNA samples from 38 CLL patients were analysed by Southern blot hybridization using JH and C mu gene probes. In order to characterize the genetic basis for the multiband pattern, we molecularly cloned the immunoglobulin heavy chain genes of one of the patients whose leukaemic DNA sample demonstrated three hybridizing JH bands and a loss of the germline band. The cloned rearranged immunoglobulin genes could be divided, based on the restriction mapping and the hybridization with the various probes, into two basic patterns representing two alleles. In one of the cloned rearranged immunoglobulin genes a secondary rearrangement occurred that resulted in the addition of 300 base-pair long sequence into the switch region, and the creation of a HindIII restriction site. The results of the study suggest that clonal evolution occurs in some CLL, and that many of these neoplasms are indeed oligoclonal due to the accumulation of secondary genetic changes. PMID- 8217795 TI - Occurrence of point mutations in p53 gene is not increased in patients with acute myeloid leukaemia carrying an activating N-ras mutation. AB - The frequency of simultaneously detecting N-ras and p53 gene mutations was studied in leukaemia cells of patients with acute myeloid leukaemia (AML) or with myelodysplastic syndrome (MDS). Using in vitro DNA amplification followed by oligonucleotide hybridization analysis, 45 AML and six MDS patients were screened for activating mutations in codons 12, 13 and 61 of N-ras. Ten of them (eight AML and two MDS) were found positive. These 10 patients and 10 others without activating N-ras mutation were further analysed by direct sequencing of the amplified exons for p53 mutations and for atypical N-ras mutations. Beside the activating mutations in the N-ras gene, no additional transforming or nontransforming mutations could be detected in the N-ras. However, exon 7 of p53 was mutated in two AML patients without activating N-ras mutation. These data show that p53 mutations occurred with half the frequency of N-ras mutations in AML and that no positive correlation could be found between the onset of mutations in N-ras and p53 genes. PMID- 8217796 TI - The presence of messenger RNA for HLA class I in human platelets and its capability for protein biosynthesis. AB - In order to determine whether platelets contain specific messenger RNA encoding for HLA class I molecules, polymerase chain reaction (PCR) was performed with RNA from different platelet donors. Two amplified 300 bp and 279 bp cDNA fragments were obtained which encompassed sequences from 321 to 620 and from 795 to 1073. The 300 bp fragment encodes exon 2 and exon 3, the 279 bp encodes a portion of exon 4, exon 5, exon 6 and a portion of exon 7. A 300 bp nested PCR product from one donor, that encoded for the highly polymorphic region alpha 2, was cloned and sequenced. The resulting nucleotide sequences fitted to the expected sequence for HLA B*3801 of this donor. Sequence analysis of the 279 bp PCR product demonstrated the presence of exon 5 encoding for the 117 bp transmembrane domain. In addition, de novo protein biosynthesis was studied by radioimmunoprecipitation of HLA class I molecules from 35S-methionine metabolically labelled platelet lysates with a monoclonal antibody (mab) w6/32 specific for a monomorphic epitope on the heavy chain of HLA class I antigens. Analysis of the immunoprecipitates on SDS polyacrylamide gel electrophoresis showed a specific band with apparent molecular weight (M(r)) of 44 kD corresponding to integral membrane HLA protein. On the basis of these results, we conclude that platelets contain specific messenger RNA encoding for HLA class I molecules and have the capability to synthesize the integral HLA membrane protein. PMID- 8217797 TI - Neonatal thrombocytopenia and hidden maternal autoimmunity. AB - Severe transient thrombocytopenia was observed in 17 newborns delivered by 11 mothers who persistently exhibited normal platelet counts and had no previous immunological or platelet disorder. Maternofetal alloimmunization as well as other causes for fetal thrombocytopenia were ruled out. A specific circulating autoantibody directed against the platelet glycoprotein Ib/IX complex was found in 10/11 mothers and in 3/4 offspring. After delivery, maternal compensated thrombocytolysis and/or hypersplenism were demonstrated by 111Indium labelled platelet studies in 10/11 women. The association of a compensated thrombocytolysis and of a specific maternal circulating antiplatelet autoantibody makes likely the diagnosis of mild maternal chronic autoimmune thrombocytopenic purpura (AITP) only expressed by the fetal or neonatal thrombocytopenia. The finding of anti-IbIX autoantibody in control women who gave birth to neonates without thrombocytopenia raises the question of the incidence and clinical significance of such antibodies which could be natural autoantibodies as well as associated with compensated thrombocytolysis or with overt immune thrombocytopenia. The cause of the discrepancy between the fetal and maternal platelet status, which could be explained by a different conformational state of fetal as compared to adult GP Ib/IX, deserves further investigation. PMID- 8217798 TI - The clinical outcome of autoimmune thrombocytopenic purpura patients is related to their T cell immunodeficiency. AB - In this work we have furthered the understanding of the alterations of T lymphocytes from 29 patients with active autoimmune thrombocytopenic purpura (ATP) and the clinical significance of their lymphocytes. An increased percentage of in vivo activated (CD25+ and DR+) T lymphocytes was found in ATP patients with respect to that found in 22 healthy controls. The function of these T cells measured as the proliferative response to polyclonal mitogenic signals is heterogeneously impaired in ATP patients. T lymphocytes from 65.5% (19/29) of the ATP patients showed a decreased proliferative response to these mitogenic signals. This functional alteration is associated with a redistribution of the T cell compartment in these patients' peripheral blood since a significant decrease of CD4+ T lymphocytes was found. We have also found that the impairment of the T cell function is different in the diverse clinical situations of the disease. Those with stable, untreated disease showed a marked decrease in the T cell proliferative response to mitogens. Furthermore, those patients who did not respond either to steroids or to splenectomy showed significantly reduced T lymphocyte blastogenesis after phytohaemagglutinin (PHA) stimulation in comparison to that found in responding patients. PMID- 8217799 TI - Expression of GpIb on plasma cells in a patient with monoclonal IgG and acquired von Willebrand disease. AB - To get insights into the pathogenesis of acquired von Willebrand disease associated with plasma cell dyscrasias, we searched for the expression of the physiological von Willebrand factor receptor, the GpIb/GpIX complex, on bone marrow plasma cells. The monoclonal spike in our patient corresponded to IgG kappa molecules; there was no plasma inhibitor to vWF:Ag or vWF:RiCoF. The bone marrow contained 1-2% plasma cells. Fresh bone marrow cells or plasma cells enriched bone marrow cells after a 48 h in vitro culture in the presence of interleukin 6 were stained by an immuno alkaline phosphatase technique using monoclonal antibodies (mAb) to von Willebrand factor, GpIb alpha and beta chain, GpIIb/IIIa and Gp IX. Two different mAb to GpIb alpha chains reacted with the majority (75%) of plasma cells whereas all other reagents yielded no staining. Malignant plasma cells from patients with multiple myeloma without haemostatic disorder were unreactive with anti-GpIb mAb. These data suggest that in some patients with acquired von Willebrand syndrome there is a GpIb mediated selective adsorption of von Willebrand factor on clonal plasma cells. PMID- 8217800 TI - Influence of demographic factors on antithrombin III activity in a healthy population. AB - Antithrombin III (AT III) activity has been measured in 9669 healthy blood donors (5525 male and 4144 female). The distribution of AT III is approximately 'normal' with mean 105.6 IU/dl and standard deviation 11.2; however, definite age and sex related variations are evident. Pre-menopausal females have lower mean AT III compared to their male contemporaries who have remarkably stable mean AT III until 45 years, after which there is a gradual decline. In contrast, post menopausal females have higher mean AT III than both males of the same age and younger pre-menopausal females. Concurrent hormone replacement therapy inhibits this rise. The use of hormonal preparations is associated with a 4 IU/dl reduction of mean AT III in younger females but not in those over 30 years. Smoking may result in a mild increase in AT III of doubtful clinical significance. On-going genetic and family studies are expected to predict a prevalence rate of congenital AT III deficiency in excess of the previously reported figure of 0.02%. The authors consider these observed variations as minor and recommend the use of a single reference range for AT III activity, but that particular care be taken when interpreting results in pill-taking females and the elderly. PMID- 8217801 TI - Improvement of mouse beta thalassaemia by hydroxyurea. AB - The present report provides evidence that hydroxyurea (HU) improves the beta thalassaemic phenotype in mice receiving 200 mg/kg/d for 30 d. The haematocrit rose from 29 +/- 3% at day 0 to 37 +/- 4% at day 30 (P < 0.05), despite myelosuppression and decreased reticulocyte counts. The beta minor/alpha ratio of globin chain synthesis increased from 0.78 at day 0 to 0.97 at day 30 (P < 0.001). Membrane defects improved: the proportion of bound alpha chains decreased, the proportion of spectrin and ankyrin increased and red cell deformability also increased. PMID- 8217802 TI - Long-term survival and cure after marrow transplantation for congenital hypoplastic anaemia (Diamond-Blackfan syndrome). AB - Four patients with Diamond-Blackfan syndrome (congenital hypoplastic anaemia) whose disease was resistant to corticosteroid treatment and who were red blood cell transfusion-dependent, were given marrow grafts from allogeneic human leucocyte-antigen (HLA)-identical siblings. The patients were conditioned with regimens including cyclophosphamide and busulfan. Three of four patients had sustained and complete marrow engraftment. One patient showed early signs of haematopoietic recovery but died on day 35 of pulmonary toxicity. The three surviving patients are well with normal haematopoiesis and Karnofsky performance scores of 100%, 3.0, 7.4 and 10.6 years after transplantation. Congenital hypoplastic anaemia can be treated successfully by allogeneic marrow grafts. PMID- 8217803 TI - An alternative strategy for identification of type IIA VWD mutations. AB - A 306 base pair segment of the von Willebrand's factor (VWF) gene between nucleotides 4627 and 4932 was amplified by PCR using DNA from a type IIA VWD patient. The amplified DNA was cloned in the plasmid pCRII. Clones of the VWF gene and pseudogene were distinguished by their KpnI restriction patterns. A series of six VWF gene clones was sequenced. A single C to T point mutation at nucleotide 4789 resulting in the substitution of arginine 834 by tryptophan was identified in four clones. This mutation, which destroys a BstEII restriction site, was also detected in amplified DNA of affected relatives of the patient. The method described avoids difficulties associated with strategies employed previously for identification of VWD mutations. PMID- 8217804 TI - A tumour-associated antigen expression in human haematological malignancies. AB - Objective responses obtained with high-dose in vivo recombinant interleukin 2 (r IL2) in some leukaemic patients suggest among other hypotheses that blasts might express tumour rejection antigens potentially recognized by cytolytic T lymphocytes. Such antigens have been described in human melanomas and the MAGE-1 gene, coding for a tumour rejection antigen was recently identified. This gene is expressed in various solid tumours, but not in normal cells. We have screened a panel of haematological malignancies by reverse transcription and PCR and we report that MAGE-1 is not expressed in the blasts from 48 patients whereas three cell lines derived from leukaemias express this gene. PMID- 8217806 TI - Familial MDS with 5q- abnormality. AB - Abnormalities of chromosome 5 and 7 are frequently found in primary MDS. Cases with familial monosomy 7 are well recognized, but there are no reports of familial MDS with deletion of 5q. We describe two sisters, aged 38 and 36 years, both of whom had MDS and interstitial deletion of 5q. The occurrence of this chromosomal abnormality reinforces the concept of tumour suppressor gene hypothesis in some cases with familial MDS. PMID- 8217805 TI - Parvovirus B19-associated haemophagocytosis in Evans syndrome: aplastic crisis accompanied by severe thrombocytopenia. AB - A 36-year-old man who had been treated for Evans syndrome (ES) developed an aplastic crisis caused by acute human parvovirus B19 (HPV) infection. Profound thrombocytopenia (8.0 x 10(9)/l) followed with a sudden increase in platelet associated IgG (PAIgG) (1376.9 ng/10(7) plts). Bone marrow examination revealed a considerable number of haemophagocytic histiocytes without any disturbance of megakaryopoiesis. To our knowledge this is the first case of aplastic crisis with virus-associated haemophagocytosis in a patient with ES, which provides an interesting insight into the mechanisms for thrombocytopenia in HPV infection. PMID- 8217807 TI - The bone marrow in murine AIDS. AB - In order to increase the understanding of blood cytopenias in HIV infection we have investigated the bone marrow in murine AIDS. C57BL/6 mice infected with the LP-BM5 retrovirus show a decrease in cellularity, numerous haemophagocytic histiocytes, a reduction of all erythroid precursor cells, an increase in eosinophil number and an increase in lymphocytes. Immunostaining with an anti Pr60gag antibody shows that the majority of bone marrow cells express the viral protein. Thus, the bone marrow in MAIDS has many similarities with the bone marrow from patients with advanced AIDS and may prove useful as a model for therapy aimed at treating blood cytopenias. PMID- 8217808 TI - CAMPATH-1 monoclonal antibody therapy in severe refractory autoimmune thrombocytopenic purpura. AB - Six patients with autoimmune thrombocytopenic purpura (three of whom had CLL/NHL and one previous Hodgkin's disease) refractory to conventional therapy were treated with an antilymphocyte monoclonal antibody directed at CDw52 (CAMPATH-1). We observed response in four of the five evaluable patients; in three patients the response has lasted more than 4-9 months. However, response did not occur in most cases until 4-6 weeks after the commencement of the antibody therapy, suggesting that the mechanism of action is probably that of immune modulation. PMID- 8217809 TI - Isolation of human herpesvirus 7 from a child with symptoms mimicking chronic Epstein-Barr virus infection. AB - Human herpesvirus-7 (HHV-7), which is a newly identified human herpesvirus with an unknown pathologic role, was isolated from a 5-year-old boy suffering from fever, hepatosplenomegaly and pancytopenia. Although the clinical course was similar to that of chronic active Epstein-Barr virus infection, no viruses other than HHV-7 were isolated. This finding raises the possibility that HHV-7 played a pathogenic role in the present patient. PMID- 8217810 TI - An unusual variant of congenital dyserythropoietic anaemia with mild maternal and lethal fetal disease. AB - An unusual variant of congenital dyserythropoietic anaemia is described presenting as mild haemolytic anaemia with multinucleated erythroblasts in the marrow of the proband. The outcome of her non-consanguineous pregnancy was a third trimester, in utero, fetal demise. The hydropic fetus had dyserythropoiesis with circulating multinucleated erythroblasts, and haemosiderosis. Re-evaluation of the proband revealed a variant of congenital dyserythropoietic anaemia with an inheritance pattern, and with morphological, serological and biochemical features which are not consistent with any of the three described variants of congenital dyserythropoietic anaemias. PMID- 8217811 TI - Haematological disorders and occupational hazards: a British Society for Haematology/Health and Safety Executive study. AB - During a 3-year period 229 patients in the U.K. with haematological disorders thought to be associated with occupational hazards were notified to the British Society for Haematology/Health and Safety Executive office. Most were suffering from malignant or premalignant states or aplastic anaemia. Benzene and ionizing radiation were the most common agents recorded. While no estimate can be made of the incidence of chemical or radiation induced disease at the present time, the data suggests that routine documentation of exposure at work is an important step in allowing more specifically focused studies. PMID- 8217812 TI - The rhythmic paradoxical eruption spectrum in the AIDS era. PMID- 8217813 TI - Irradiation of transfused products in prevention of third party mediated GVHD and graft rejection. PMID- 8217814 TI - Management of asplenic patients. PMID- 8217816 TI - ZB51: a monoclonal antibody reactive with human plasma cells. AB - Several monoclonal antibodies have been raised in the past which react with human plasma cells but they have all shown additional reactions with other cell types. In this paper we describe a new monoclonal antibody, ZB51, which recognizes an intracellular antigen in normal plasma cells in cryostat tissue sections and cell smears, and which also reacts with neoplastic cells in most cases of myeloma and with plasma cell lines. The antibody shows minimal reactivity with a few eosinophils and myelocytes in bone marrow and stains a myeloid cell line. Whilst normal epithelium is not labelled, antibody ZB51 stains two carcinoma cell lines. Although it was not possible to characterize the target antigen in terms of molecular weight, the reactivity of antibody ZB51 with normal and neoplastic plasma cells makes it a useful new immunocytochemical reagent. PMID- 8217815 TI - Accumulation of 5-methyltetrahydrofolic acid and folylpolyglutamate synthetase expression by mitogen stimulated human lymphocytes. AB - The accumulation of 5-methyl[3H]tetrahydrofolic acid (5CH3[3H]FH4) by phytohaemagglutinin stimulated lymphocytes (PHA-L) cultured in folate free media was investigated to determine the mechanism of uptake of 5CH3FH4 and the requirement of the cells for this vitamin as assessed by monitoring de novo thymidine synthesis. When grown in 20 nM 5CH3[3H]FH4 PHA-L accumulate radiolabel at a rate of 0.04 pmol/h/10(6) cells. This doubles the endogenous folate pool of unstimulated cells (0.6 +/- 0.16 pmol/10(6) cells) in about 15 h. Uptake proceeded via a saturable process, independent of a high affinity folate receptor as assessed by ligand binding and by Northern and Western blot analysis. However, transport was blocked by probenecid, which is consistent with an anion carrier mechanism. Unstimulated cells lacked folypolyglutamate synthetase (FPGS) activity and did not express significant amounts of FPGS mRNA. After 48 h of mitogen stimulation there was a 4-10-fold increase in FPGS mRNA and folypolyglutamate formation (Glu > or = 5) was essentially simultaneous with 5CH3[3H]FH4 transport. Increasing extracellular folate to 2 microM only increased intracellular folate 8 fold, but the length of the folylpolyglutamates decreased. The increased folate did not increase de novo thymidine synthesis compared to cells grown in physiological folate. We conclude that mitogen stimulation activates the process(es) for folate accumulation, especially FPGS, and that physiological uptake (0.04 pmol/h/10(6) cells) is adequate for meeting the cells' need for the vitamin. PMID- 8217817 TI - Subcellular fractionation studies indicate an intracellular localization for human monocyte specific esterase (MSE). AB - Human monocyte-specific esterase (MSE) is one of the few haemopoietic cell enzymes that show absolute lineage restriction. Although the function of MSE has yet to be deduced, its potential role in tumour cell killing has stimulated particular interest. Knowledge of subcellular localization of MSE is fundamental to understanding its function and, in this context, it is widely believed that MSE is expressed as a plasma membrane ectoenzyme; a contention that is largely based upon experiments which examined fixed cells by ultrastructural cytochemistry. However, as recent molecular studies of human MSE indicate, a number of inconsistencies between its structure and a membrane localization, we applied the techniques of phase separation in the non-ionic detergent Triton X 114 and differential centrifugation to further investigate whether this particular esterase species is membrane-bound or associated with an intracellular organelle. These studies provide strong evidence that MSE is in fact a soluble intracellular enzyme that is almost certainly located within the lumen of the endoplasmic reticulum. PMID- 8217818 TI - Evaluation of late cardiotoxicity with pulsed Doppler echocardiography in patients treated for Hodgkin's disease. AB - The impact of valvular, myocardial and pericardial abnormalities on cardiac haemodynamics in patients treated for Hodgkin's disease with COPP/ABVD with and without mediastinal irradiation was determined in 49 patients 2-10 years after induction therapy. Diagnostic procedures to evaluate cardiac function consisted of history, physical examination, exercise bicycle stress test, M-mode two dimensional and pulsed Doppler echocardiography. No patient reported symptoms related to cardiomyopathy, and only one of the 49 had evidence of coronary heart disease. Pericardial thickening was seen on echocardiograms in 19/49 patients (38.8%), valvular thickening in 21/49 (42.9%), and reduced fractional shortening in 9/49 (18.4%). The Doppler-derived mean E and A (+/- SD) of transmitral flow were 0.75 +/- 0.14 m/s and 0.56 +/- 0.09 m/s, respectively, in patients receiving chemotherapy and 0.81 +/- 0.19 m/s and 0.63 +/- 0.20 m/s in those with additional mediastinal irradiation. There was no statistically significant difference between mean E and A in transmitral flow in patients treated for Hodgkin's disease and control subjects. Furthermore, the transtricuspid and hepatic vein flow velocities did not differ significantly. Although the present study demonstrates high frequencies of pericardial and valvular thickening in patients treated for Hodgkin's disease with the COPP/ABVD regimen with or without mediastinal irradiation, it showed no impact on cardiac flow velocities. The abnormalities might thus be of minor clinical relevance in these patients. PMID- 8217819 TI - Subclinical autonomic dysfunction in patients with Hodgkin's disease and non Hodgkin's lymphoma. AB - A prospective study was carried out to determine the prevalence of autonomic dysfunction in patients with lymphoma, and to assess the effect on this of chemotherapy. Twenty consecutive patients presenting with Hodgkin's disease, high grade non-Hodgkin's lymphoma, or low-grade non-Hodgkin's lymphoma were studied. All had advanced disease, requiring combination chemotherapy which included the use of vinca alkaloids. Clinical assessment and standard cardiovascular autonomic function tests were carried out prior to and following completion of chemotherapy. Although no patients had clinical evidence of autonomic neuropathy at presentation, 16 (80%) had abnormal cardiovascular autonomic function tests. There was no correlation with the presence or absence of mediastinal disease. There was significant improvement in autonomic scores with treatment despite the use of drugs of known neurological toxicity. Some patients showed residual abnormalities of autonomic function despite disease resolution. We suggest that subclinical autonomic dysfunction is common in patients with lymphoma, and probably represents a paraneoplastic syndrome--the pathogenesis and prevalence of which deserve further study. This phenomenon may predispose patients with lymphoma to develop gastrointestinal and genitourinary dysfunction, or postural hypotension, and should be considered during the evaluation of the neurotoxicity of chemotherapy regimens. PMID- 8217820 TI - Lymphotoxin, tumour necrosis factor and interleukin-6 gene transcripts are present in Hodgkin and Reed-Sternberg cells of most Hodgkin's disease cases. AB - Tissue specimens from 26 cases of Hodgkin's disease (HD) and six HD-derived cell lines were analysed for tumour necrosis factor (TNF), lymphotoxin (LT), and interleukin (IL)-6 RNA transcripts by in situ hybridization, in some cases subsequent to immunohistology for CD30 antigen. LT and TNF transcripts were found in tumour cells of all cases; IL-6 gene transcripts were detectable in 19/23 cases. Presence of RNA specific for these cytokines was not correlated with any of the following parameters: sex, symptoms and histotype, as well as immunophenotype and association of the tumour cells with Epstein-Barr virus. Rather, the presence of LT, TNF and IL-6 transcripts appeared to characterize Hodgkin and Reed-Sternberg cells in general, supporting concepts which suggest that HD represents a malignancy of cytokine secreting activated cells, and that many of the features distinguishing HD from other malignant lymphomas may ultimately be due to expression of cytokines. LT and TNF RNA transcripts were also found in five HD-derived cell lines, whereas supernatants of these cell lines contained high levels of LT, but low or undetectable levels of TNF activity. This suggests that, although not detectable at the level of RNA transcripts, differences between HD cases may exist on the level of cytokine gene transcript processing, translation and polypeptide secretion. PMID- 8217821 TI - Myelodysplastic syndrome with eosinophilia in bone marrow. Gunma Haematology Study Group. AB - Clinical features were investigated in 114 patients with de novo myelodysplastic syndrome (MDS) diagnosed over the past 10 years, and eight cases (7%) were complicated with eosinophilia in the bone marrow. Two patients had refractory anaemia (RA), five had RA with excess of blasts (RAEB), and one had RAEB in transformation. Their bone marrow cells exhibited tri-lineage dysplasia and morphological abnormalities in eosinophils. Cytogenetics revealed major karyotype abnormalities (MAKA) in five patients. Survival durations were significantly shorter than those of other MDS patients. Our study suggests that marrow eosinophilia in MDS is strongly related to the coexistence of MAKA. PMID- 8217822 TI - Impact of leucocyte-depleted blood components on the haematological recovery and prognosis of patients with acute myeloid leukaemia. Finnish Leukemia Group. AB - Use of leucocyte-depleted blood components reduces refractoriness to platelet transfusions, but the cost-effectiveness of this policy has been in doubt. We retrospectively analysed data of 115 patients with acute myeloid leukaemia (AML), treated according to a standardized cytostatic protocol. Fifty patients had received standard (STD) platelet concentrates (PCs) and red blood cell concentrates (RBCs). Sixty-five patients had received leucocyte-depleted (L-D) components, with fewer than one million leucocytes per unit. Refractory patients (22% of the STD group and 3% of the L-D group) were excluded from further observations. There were no differences between the groups during the first cytostatic treatment period. Thereafter, significantly fewer PCs and RBCs were transfused to the L-D group. In the L-D group, granulocytopenia (< 0.5 x 10(9)/l) and thrombocytopenia (< 50 x 10(9)/l) were shorter, the lowest leucocyte counts were higher, serious infections were less common (44% v 59%), and the patients spent fewer days in hospital. The median relapse-free survival (RFS) was longer in the L-D group than in the STD group. We conclude that leucocyte depletion of blood components has favourable effects on the recovery of haematopoiesis, consumption of blood components, occurrence of serious infections, and relapse free survival in AML. PMID- 8217823 TI - Direct sequence analysis of TCR V delta 2-D delta 3 rearrangements in common acute lymphoblastic leukaemia and application to detection of minimal residual disease. AB - T cell receptor delta chain (TCR delta) gene rearrangements were studied by Southern blot analysis in 36 patients with common acute lymphoblastic leukaemia, including 14 adults and 22 children. The majority of patients (68%) had either a rearrangement or deletion of one or more TCR delta genes. The most frequent rearrangement involved a partial recombination of V delta 2 to D delta 3 (55%). D delta 2-D delta 3 rearrangements were present in five patients (14%). To investigate the TCR delta rearrangement as a tumour marker in minimal residual disease studies, presentation samples from 18 patients were amplified by PCR and directly sequenced. Although the size of the V delta 2-D delta 3 junction varied by only 40 bp, sequence analysis showed extensive diversity. This was derived from four factors: deletion of the 5' end of D delta 3 gene (15/18) and 3' end of V delta 2 gene (16/18); the presence of D delta 2 sequences (6/18); insertion of N nucleotides (15/18); association of P nucleotides with intact V delta 2 and D delta 3 genes (5/18). N nucleotides were the major feature, contributing to 75% of the junction. D delta 1 sequences were not involved. Twenty base oligonucleotide probes, constructed from the junctional sequences, were capable of detecting residual tumour cells at the 10(-4) sensitivity level. Cross hybridization studies confirmed the probes to be clone specific. Longitudinal studies on patients undergoing treatment were capable of detecting tumour in remission samples. PMID- 8217824 TI - Identification of nine novel mutations in type I antithrombin deficiency by heteroduplex screening. AB - We have utilized DNA heteroduplex detection as a method for screening sequences of the antithrombin (AT) gene for the presence of mutations. Affected individuals from 41 kindreds with type Ia antithrombin deficiency were investigated. Heteroduplexes were detected in 12 cases; direct sequencing of the appropriate exons revealed nine cases with novel mutations, and two with previously described mutations. In addition, a new polymorphism in the 5' untranslated region was characterized. The defects included minor insertions and deletions which lead to the removal of intact codons or premature termination, and single base substitutions leading to premature termination or amino acid substitution. In all cases, the affected individuals were heterozygous for the defect and variant AT protein was not detected. In keeping with previous reports the defects associated with type Ia AT deficiency are extremely heterogeneous, the vast majority being point mutations. This study also demonstrates the efficiency of hydrolink gel electrophoresis as a method of screening for unknown mutations by heteroduplex detection. PMID- 8217825 TI - Detection of a molecular defect in 40 of 44 patients with haemophilia B by PCR and denaturing gradient gel electrophoresis. AB - Oligonucleotides were computer designed to amplify by the polymerase chain reaction (PCR) the coding region, splice junctions, 112 bp of the 5' flanking region and 279 bp surrounding the polyadenylation site of the factor IX gene for analysis by denaturing gradient gel electrophoresis (DGGE). Forty-four unselected haemophilia B patients were studied of whom 24 had severe haemophilia and 20 had a mild to moderate form of the disease. Potential mutations were identified in 40 (91%) of the 44 cases. A defect could not be detected in three severe and one mild haemophiliac by DGGE analysis and direct sequencing of all the PCR fragments from these patients revealed no nucleotide alteration supporting the DGGE results. A total of 37 point mutations, two complete gene deletions and a duplication of 26 bp were found. The 37 point mutations included 35 single nucleotide substitutions, a deletion and an insertion of one nucleotide. The 35 single nucleotide substitutions included 26 missense mutations, seven nonsense mutations, a G (-6) to A transition in the promoter region and a G (30154) to A transition within the donor splice site of the last intron. Fifteen of these nucleotide substitutions involved CpG dinucleotides. Fifteen point mutations were found at codons where nucleotide substitutions had not been detected before. An insertion of a single nucleotide T at position 6370 and deletion of a G at nucleotide 30845 resulted in frameshift mutations creating stop codons at amino acid positions -2 and 250, respectively. A duplication of 26 bp (17747-17772) in exon V was found in a severe haemophilia patient resulting in a termination codon in exon VI. The detection of the mutation by the combined use of PCR, DGGE and direct sequencing was important for carrier diagnosis of 20 families with no prior history of haemophilia B. PMID- 8217826 TI - Markers of procoagulant imbalance in patients with localized melanomas and autoimmune disorders. AB - Hypercoagulability can be defined as a condition of procoagulant imbalance due to heightened enzymatic activation of coagulation zymogens, but with no laboratory evidence of fibrin deposition nor clinical signs of thrombosis. The imbalance can be detected by measuring the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), fibrinopeptide A (FPA) and thrombin-antithrombin III (TAT) complexes. The aims of this study were to establish the frequency of existence and biochemical pattern of hypercoagulability in patients with cancer and autoimmune disorders, clinical conditions associated with an increased risk of thrombosis, and to ascertain the most sensitive method for its diagnosis. In approximately one fourth of the patients hypercoagulability was identified by finding high levels of FPA F1 + 2 or TAT unaccompanied by signs of fibrin deposition (expressed by normal levels of D-dimer). In a smaller proportion of patients (approximately 10%), the concomitant presence of high levels of D-dimer indicated that the activation of the coagulation cascade had gone beyond the stage of heightened enzymatic activity to the point of cross-linked fibrin deposition. Of the markers used to detect hypercoagulability. FPA seems to be the most sensitive, being significantly increased in all clinical conditions studied. PMID- 8217827 TI - Whole blood platelet aggregation and coagulation factors in patients with systemic sclerosis. AB - It is unclear whether the changes in platelet function which are observed in systemic sclerosis are a primary characteristic of this disease or whether they occur secondary to vascular changes. Whole blood platelet aggregation was studied in 26 patients with systemic sclerosis, normal subjects matched for age, sex and secondary characteristics, 19 patients with Raynaud's disease and 19 patients with systemic lupus erythematosus. Plasma levels of fibrinogen, von Willebrand factor antigen and factor VIII:C were also measured. Systemic sclerosis was associated with a significant (P > 0.001) enhancement of the sensitivity of platelets to collagen. In contrast, significant enhancement of the response to either ADP or adrenaline was not observed. Enhanced sensitivity to collagen was not associated with the presence of either Raynaud's disease or systemic lupus erythematosus. Systemic sclerosis was associated with significantly raised levels of von Willebrand factor antigen and fibrinogen. On an individual patient basis, von Willebrand factor antigen was related to the severity of the disease whereas platelet sensitivity to collagen was not. In conclusion, this study suggests that the enhanced sensitivity to collagen which occurs in systemic sclerosis is due to a primary change in the platelet and that this change can combine with elevated levels of adhesive proteins. PMID- 8217828 TI - Vitamin K metabolism and vitamin K1 status in human liver samples: a search for inter-individual differences in warfarin sensitivity. AB - Vitamin K-dependent parameters in human liver samples were investigated to find a clue to the inter-individual differences in sensitivity for oral anticoagulants. Vitamin K epoxide reductase and vitamin K-dependent carboxylase activity differed 2-3-fold between the samples. Microsomal warfarin binding correlated significantly with the reductase activity. Microsomal vitamin K epoxide reductase of the different samples showed equal sensitivity for warfarin inhibition, I50 about 0.1 microM. Vitamin K epoxide reductase activity stimulated by NADH/lipoamide and microsomal lipoamide dehydrogenase activity showed higher inter-subject variability than the reductase activity by itself. Liver vitamin K1 levels varied 4-5-fold. Total and liver microsomal vitamin K1 levels were correlated. One of the liver samples was obtained from a donor anticoagulated with phenprocoumon and additionally treated with vitamin K1. High levels of the vitamin and its epoxide were present. Phenprocoumon was essentially irreversibly bound to the microsomes. In general the results confirm inter-individual differences in the hepatic vitamin K-dependent systems; the differences as such were found to be small. However, as the various parameters can work synergistically in the same direction, they may well account for the wide dose range observed in oral anticoagulant therapy. PMID- 8217829 TI - Blood platelet heterogeneity: evidence for two classes of platelets in man and rat. AB - The platelet population of man and rat can be divided into two classes of about equal size on the basis of presence/absence of an acid phosphatase which acts on para-nitrophenylphosphate (a PNPase), at pH 5. The cytochemical reaction product is in the platelet cytoplasmic matrix, without apparent association with organelles or membrane systems. We could not relate differences in staining to differences in function: all cells responded the same to activation by thrombin, ADP, or collagen, in fibrinogen binding to activated platelets, by endocytosis of fluid-phase tracers, and in internalization of latex particles. With respect to possible physiological substrates for the PNP-ase, there was no reaction product from beta-glycerophosphate, AMP, ADP, ATP, GTP, CMP, IMP, cAMP, creatine phosphate, and inositol phosphates, and the enzyme was not inhibited by 40 mM lithium. There was reaction product from tyrosine phosphate suggesting that the physiological substrate for PNP-ase is tyrosine phosphate. In rat bone marrow, megakaryocytes also were of two classes, PNPase positive and PNPase negative, suggesting that different classes of platelets arise from different classes of megakaryocytes. PMID- 8217830 TI - Platelet activation induced by an antiplatelet autoantibody against CD9 antigen and its inhibition by another autoantibody in immune thrombocytopenic purpura. AB - In a patient with immune thrombocytopenic purpura (ITP), we found a novel platelet-activating IgG (act-IgG) and an inhibitory IgG (inhi-IgG) that prevented activation induced by both CD9 monoclonal antibody (mAb) and the act-IgG. Purified IgG from the patient plasma caused a rise in [Ca2+]i and the aggregation of normal platelets, and bound to a 24 kD membrane protein. This aggregation was inhibited by aspirin, staurosporine, an inhibitor of protein kinase C, and F(ab')2 fragments of MALL13, a CD9 mAb. When the platelet count of this patient rose to normal range, the act-IgG disappeared. About 2 weeks later, the relapse of thrombocytopenia was observed. The purified IgG obtained in this period did not activate platelets but inhibited both the rise in [Ca2+]i and platelet aggregation stimulated by NNKY 1-19, a CD9 mAb, as well as the act-IgG, and bound to a 40 kD membrane protein. The inhi-IgG prevented the binding of IV-3, a mAb against Fc gamma receptor II (Fc gamma RII), but did not prevent the binding of NNKY 1-19 to its antigen. We suggest that the activating autoantibody recognized CD9 antigen and activated both the thromboxane- and phospholipase C-dependent pathways, while the inhibitory autoantibody recognized the Fc gamma RII and inhibited CD9 antibody-induced platelet activation mediated via this receptor. PMID- 8217831 TI - Heparin-associated thrombocytopenia: immune complexes are attached to the platelet membrane by the negative charge of highly sulphated oligosaccharides. AB - The interaction of sulphated oligosaccharides (SO) with platelets and the antibody of heparin-associated thrombocytopenia (HAT type II) was investigated. 3H-heparin binding to platelets was inhibited by different SO, depending on their grade of sulphation. Dextran sulphate, pentosan polysulphate, and heparin were more effective than were LMW heparins. De-N-sulphated heparin and a LMW heparinoid (Org 10172) had no effect. Platelets preincubated with high-grade SO and washed, released serotonin in the presence of HAT sera without additional heparin. Platelets preincubated with HAT sera and then washed were not activated when heparin was added. Only high-grade SO which inhibited heparin binding to platelets caused platelet activation with HAT sera. However, low- and high-grade SO in high concentrations (0.11 g/l) inhibited serotonin release induced by HAT sera and heparin. 32P-phosphorylation of platelet proteins was enhanced by HAT IgG and heparin and by heat-aggregated IgG, and was inhibited by the moab IV.3. High SO concentrations inhibited only the effect of HAT-IgG and not that of aggregated IgG. We assume that the antigen in HAT involves a releasable platelet protein with a binding site for SO. This was corroborated by studies with an anti platelet factor 4 antibody causing Fc-receptor dependent platelet activation inhibitable by high SO concentrations. PMID- 8217832 TI - Concurrent label method with 111In and 51Cr allows accurate evaluation of platelet viability of stored platelet concentrates. AB - The precision and reproducibility of 111In and 51Cr platelet radiolabel agents for in vivo kinetic studies of stored platelet concentrates (PC) were investigated. The objective was to develop a precise method with concurrent labelling of two platelet populations using different isotopes, which would allow identification of small differences in in vivo platelet quality. Identical labelling procedures were used to investigate the effects of PC storage age, different methods of red cell (RBC) and white cell (WBC) contamination correction, and label elution correction on the results of 111In and 51Cr kinetic studies. 111In and 51Cr platelet survival curves from the same PC, even when uncorrected for elution and RBC contamination, exhibited excellent correlation, irrespective of the age of the concentrate and its viability. However, slightly higher, but statistically significant, post-infusion per cent recoveries with 51Cr labelled platelets were found. Two factors were identified as the cause for this difference. There was a higher affinity of contaminating RBC/WBC in PC for 51Cr than for 111In. With determination of RBC/WBC activity by centrifugation/density separation, RBC/WBC fractions from the injectate were found to contain 12.6 +/- 3.8% v 7.1 +/- 3.6% of total 51Cr and 111In activity, respectively, in 20 studies. In addition, there was a significantly higher 111In activity in plasma immediately post-infusion than with 51Cr, 5.2 +/- 1.3% v 2.8 +/- 1.6%, respectively, suggesting more label elution or carryover. After correction for the activity of RBC/WBC and for elution or carryover, essentially identical 51Cr/111In platelet survival curves were found. In 31 stored PC studies, the absolute average difference between 51Cr and 111In per cent recoveries was only 4 +/- 3% in a group of donors whose platelet recoveries ranged from 10% to 80%. Similarly, the average difference between 51Cr and 111In survival was only 8 +/- 4 h within a range of survivals from 40 to 220 h. In conclusion, after correction for elution and contaminating RBC/WBC binding, these studies show that 51Cr and 111In may be used interchangeably for labelling of stored PC, and that small differences between test and control platelets could be reliably detected using concurrent labelling with simultaneous infusion. PMID- 8217834 TI - Avascular necrosis after treatment of aplastic anaemia with antilymphocyte globulin and high-dose methylprednisolone. AB - Avascular necrosis of bone (AVN) occurring in patients with aplastic anaemia (AA) treated with antilymphocyte globulin (ALG) followed by high-dose methylprednisolone (HDMP) has been studied retrospectively. Out of 49 patients treated at two centres, seven have developed AVN at a median of 14 months (range 6-30) following treatment. The cumulative incidence of AVN is 21% (95% confidence intervals 7-35%). The hip was involved in six patients, bilaterally in five. Two patients had more than two joints affected. Surgical intervention was necessary in five patients, three of whom required total hip replacement. In contrast, there were no cases of AVN in a historical group of 61 patients with aplastic anaemia treated with an identical regimen of ALG but using a short course of low dose prednisolone. Lack of convincing evidence for benefit, the considerable morbidity from AVN, and increased risk of early life-threatening infection, suggest that high-dose methyl prednisolone should be omitted from ALG treatment protocols for aplastic anaemia. PMID- 8217833 TI - A phase I/II study of prostaglandin E1 for the prevention of hepatic venocclusive disease after bone marrow transplantation. AB - We conducted a phase I/II trial of prostaglandin E1 (PGE1) for the prevention of hepatic venocclusive disease (VOD). Twenty-four patients at high risk for VOD received PGE1 at four dose levels ranging from 1.25 to 10 ng/kg/min. Severe toxicity was experienced at all dose levels and was manifested as cutaneous erythema and desquamation, severe pain in dependent extremities, fluid retention and grade 4 oedema, or hypotension. In 12/24 patients, PGE1 administration was stopped prior to day 15 due to severe toxicity attributed to the drug. Three of 12 patients who received PGE1 for the entire course of treatment and 9/12 patients whose PGE1 was stopped prior to day 15 developed severe toxicity which was attributed to PGE1 (P = 0.039). Severe toxicity attributed to PGE1 was not related to either PGE1 concentration or PGE1 clearance. Six of 12 patients whose PGE1 infusion was stopped prior to day 15 and 2/12 patients who received PGE1 for the full course of treatment developed severe VOD (P = 0.19). We conclude that PGE1 causes significant toxicity in patients undergoing marrow transplantation. The ability of PGE1 to prevent severe VOD in patients at high risk remains unproven. PMID- 8217835 TI - Degradation of human erythrocyte surface components by human neutrophil elastase and cathepsin G: preferential digestion of glycophorins. AB - Human erythrocytes treated with purified human neutrophil elastase (HNE) or cathepsin G (CathG) were analysed by serological methods and by SDS polyacrylamide gel electrophoresis followed by staining or immunoblotting with monoclonal antibodies. Both enzymes digested exhaustively glycophorins A, B and C, and HNE caused a partial digestion of band 3 protein. The degradation of other membrane proteins was not detectable by the methods used. Immunoblotting with the use of monoclonal antibodies against the defined epitopes of glycophorin A showed that HNE and CathG hydrolysed distinct peptide bonds in this antigen. The antibody PEP80, specific for the epitope in the cytoplasmic fragment of glycophorin A, gave patterns of bands which were characteristic for each of the two proteases. These bands could be distinctly identified in erythrocyte membrane samples containing only few percent of digested glycophorins. Therefore, the immunoblotting with this antibody may be useful as a sensitive assay for detecting the action of neutrophil proteases on red blood cells. PMID- 8217836 TI - Improved cytogenetic analysis of bone marrow plasma cells after cytokine stimulation in multiple myeloma: a report on 46 patients. AB - Cytogenetic analysis was successfully performed in 46 consecutive myeloma patients (40 newly diagnosed and six relapsed patients). Karyotype was performed on bone marrow cells after long-term cultures (6 d) stimulated by GM-CSF, GM CSF+IL6 or GM-CSF+IL6+IL3. Nineteen patients (41%) had cytogenetic abnormalities including 17/40 patients at diagnosis (42.5%) and 2/6 patients at relapse. Hyperdiploidy was found in 12 patients and hypodiploidy in four patients. Of the 17 newly diagnosed patients with cytogenetic abnormalities, five died from myeloma after 1-14 months and three other patients had primary drug resistance. Our results suggest that cytogenetic analysis after stimulation of cultures by cytokines detects clonal abnormalities in 40-50% of newly diagnosed myeloma patients and that these patients often have a short survival and/or primary drug resistance. PMID- 8217837 TI - Serum deoxythymidine kinase: no help in the diagnosis and prognosis of monoclonal gammopathy. AB - Serum deoxythymidine kinase activity (S-TK) was determined in the diagnostic evaluation and follow-up of patients with monoclonal gammopathy of undetermined significance (MGUS). During a 4-year period 35 patients were included in the study. Normal concentrations of S-TK were found in 33. Patients with non progressive monoclonal gammopathy kept a stable, and for the individual, a characteristic level of S-TK during several years of follow-up. A moderately elevated level of S-TK during observation did not indicate progression. Even in four out of five patients developing symptomatic multiple myeloma S-TK remained unchanged. Determination of S-TK does not give diagnostic or prognostic information in monoclonal gammopathy. PMID- 8217838 TI - Induction of TNF-alpha in patients with myelodysplastic syndromes undergoing treatment with interleukin-3. AB - The study was undertaken to analyse whether the presence or the induction of TNF alpha, a potent inhibitor of haemopoiesis, might affect the clinical response to treatment with interleukin-3 in patients with myelodysplastic syndromes. A total of 15 patients were treated with IL-3. Baseline serum TNF-alpha levels were elevated in MDS patients (14.2 +/- 2.4 pg/ml) compared to healthy controls (9.1 +/- 1.1 pg/ml). During IL-3 therapy TNF-alpha levels remained unchanged in 3/14 patients in whom platelet counts increased, while in non-responders TNF-alpha levels increased 1.9-fold (P < 0.025). These findings indicate that TNF-alpha not only is induced during IL-3 therapy in MDS patients but that this elevation might be associated with a poor platelet response to therapy. PMID- 8217839 TI - Accelerated erythroid repopulation with no stem-cell competition effect in children treated with recombinant human erythropoietin after allogeneic bone marrow transplantation. AB - We carried out a pilot study on the use of recombinant human erythropoietin (rHuEPO) to accelerate erythropoietic engraftment in paediatric patients undergoing allogeneic BMT. rHuEPO was administered intravenously at a dose of 75 U/kg per day for 30 d after transplant. Erythroid repopulation, evaluated sequentially through the serum transferrin receptor, was faster in 15 patients receiving rHuEPO than in 16 historical controls (P = 0.0003). This faster erythroid engraftment resulted in a reduction in the total number of red blood cell units required to reach transfusion independence (2.7 +/- 1.2 v 4.2 +/- 2.3, P = 0.027). No significant difference in leucocyte or platelet regeneration was observed. These findings indicate that rHuEPO administration can accelerate erythroid recovery after allogeneic BMT and reduce red cell transfusion requirements with no stem-cell competition effect. PMID- 8217840 TI - Whole mount in situ hybridization shows Endo 16 to be a marker for the vegetal plate territory in sea urchin embryos. AB - We have used whole mount in situ hybridization to analyze the pattern of expression of the gene Endo 16 in S. purpuratus embryos. The mRNA is first detectable at 18 h post-fertilization in the cytoplasm of blastomeres derived from the Veg2 6th cleavage tier. The number of Endo 16 positive cells increases gradually through the beginning of gastrulation, and these cell numbers are in agreement with estimates of the number of cells that should be in the vegetal plate at these stages. We conclude that Endo 16 expression is indeed an early vegetal plate marker and that this gene is expressed by all Veg2 tier derivatives while they are part of the vegetal plate. The progressive regionalization of Endo 16 expression that occurs in normal embryos is also seen in lithium chloride induced exogastrulae, leading to the conclusion that genetic regulation of endoderm differentiation is programmed into the vegetal plate cells once they have been specified. Finally, we report a reproducible phenomenon seen in cultures of LiCl exogastrulae, in which the tips of the everted archenterons fuse, followed by the induction of supernumerary pigment cells. PMID- 8217841 TI - Transduction of Ca2+ signals upon fertilization of eggs; identification of an S 100 protein as a major Ca(2+)-binding protein. AB - A transient increase in the level of free cytosolic Ca2+ is observed upon fertilization of the eggs of many species and is thought to represent a key event in the initiation of development. To identify components in the egg which could be involved in mediating such Ca2+ signals we searched for Ca(2+)-binding proteins in eggs of the fresh-water fish Misgurnus fossilis (loach). We show that loach eggs contain two major Ca(2+)-binding proteins which can be purified through their Ca(2+)-dependent interaction with a hydrophobic matrix. Protein sequencing revealed that the larger 18 kDa protein is calmodulin, while the smaller polypeptide of 10 kDa is a member of the S-100 protein family. This is the first report of the presence of an S-100 protein in vertebrate eggs and shows that this protein is found in two fold higher concentration than calmodulin. Since the 10 kDa protein shares 68% sequence identity with S-100 alpha from bovine brain, it can be considered as the loach homologue of mammalian S-100 alpha. During early embryonic development, de novo protein synthesis of calmodulin is observed at the earliest stages analyzed (mid-blastula), while de novo protein synthesis of the S-100 alpha homologue begins with the mid-gastrula stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217842 TI - The daughterless gene product in Drosophila is a nuclear protein that is broadly expressed throughout the organism during development. AB - The daughterless (da) gene in Drosophila functions in the regulation of at least three significant developmental pathways: sex determination, neurogenesis and oogenesis. As a member of the helix-loop-helix (HLH) family of DNA binding proteins, the da gene product appears to act as a transcription factor. Based on the genetic and molecular characterization of da, it has been proposed that the da protein (Da) functions as a generic member of this family, serving throughout development as a necessary binding partner for an assortment of other HLH proteins. As a result of temporally and/or spatially restricted expression, these binding partners would provide some regulatory specificity to the functional transcription complex. In order to participate in this way in the regulation of multiple genes, Da must be expressed in numerous times and places during development. Using anti-Da antibodies, we validate two predictions of this scenario of Da function: (1) Da protein is not only nuclear localized, but also associated with chromosomes in vivo; and (2) Da protein is widely distributed, both spatially and temporally, throughout development. With regard to the essential role of maternal da+ in progeny sex determination, little, if any, Da protein is synthesized in the maternal germline. This suggests that the female specific germline function of da+ is provided to the zygote as maternally synthesized RNA that becomes translated early in embryogenesis. PMID- 8217843 TI - Dynamic expression of the murine Achaete-Scute homologue Mash-1 in the developing nervous system. AB - The Drosophila Achaete-Scute Complex genes encode transcriptional regulators belonging to the basic-helix-loop-helix family which control early steps of development of the central and peripheral nervous systems. We have isolated two mouse homologues of Achaete-Scute Complex genes, Mash-1 and Mash-2, by using the conservation of the basic-helix-loop-helix domain in this family. In this article, we analyse the expression of Mash-1 from its onset during neurulation to adult stages by RNA in situ hybridization on whole mounts and sections. As was observed for the rat Mash-1 protein, mouse Mash-1 RNA expression is restricted to cells of the developing central and peripheral nervous systems. We have observed three successive phases in the distribution of Mash-1 transcripts in the developing central nervous system. Initially, between embryonic day 8.5 and 10.5, Mash-1 transcripts are found in restricted domains in the neuroepithelium of the midbrain and ventral forebrain, as well as in the spinal cord. Between embryonic day 10.5 and 12.5, Mash-1 expression pattern changes from a restricted to a widespread one. Mash-1 transcripts are then found at variable levels in the ventricular zone in all regions of the brain. From embryonic day 12.5 to post natal stages, Mash-1 is also expressed in cells outside of the ventricular zone throughout the brain. In addition, Mash-1 is expressed during development of the olfactory epithelium and neural retina. Overall, its expression pattern suggest that Mash-1 plays a role at early stages of development of specific neural lineages in most regions of the central nervous system and of several lineages in the peripheral nervous system. We have also compared the expression of Mash-1 and mouse Notch because their Drosophila homologues have been shown to interact genetically. The two genes show very similar expression patterns, both spatially and temporally, in the early developing brain and in the retina, suggesting that both genes may participate in the development of the same neural lineages. PMID- 8217844 TI - Incidence of cancer and mortality among workers exposed to mercury vapour in the Norwegian chloralkali industry. AB - Incidence of cancer and mortality were studied among 674 men exposed to mercury vapour for more than one year at two chloralkali plants. Mercury excretion in urine had been monitored among the workers at the two plants since 1948 and 1949. An individual cumulative urinary mercury dose was calculated, based on about 20,000 urinary mercury measurements. The incidence of cancer and the mortality were followed up from 1953 to 1989 and 1953 to 1988 respectively. The general Norwegian male population served as a reference population. There was a lung cancer excess of borderline significance (standardised incidence ratio = 1.66, 95% confidence interval = 1.00-2.59). The introduction of a 10 year latent period before developing lung cancer did not increase the incidence ratio. The excess may be partly explained by the smoking habits in the cohort or possibly by exposure to asbestos. No excess of cancer was found in the target organs for mercury toxicity--namely, the kidney and the nervous system. No significant excess mortality was found for nephritis and nephrosis or nonmalignant diseases of the nervous system. PMID- 8217845 TI - Assessment of renal dysfunction in workers previously exposed to mercury vapour at a chloralkali plant. AB - Urinary albumin concentration (U-alb) and N-acetyl-beta-D-glucosaminidase (U-NAG) and glomerular basement membrane antibodies (a-GBMs) in serum samples were measured in 77 chloralkali workers previously exposed to mercury (Hg) vapour and 53 age matched referents. The exposure ceased on average 12.3 (range 1-35) years before the study. The mean exposure time was 7.9 (range 1.1-36.2) years. The mean yearly urinary Hg concentration (U-Hg) was 531 nmol/l. The concentrations of the urinary isoenzymes NAG A (U-NAG A) and NAG B (U-NAG B) were determined in 30 highly exposed subjects and 30 referents. No differences in U-alb or U-NAG, U-NAG A, or U-NAG B were found between the groups. Higher concentrations of a-GBMs were found among subjects who stopped exposure a short time before the study, but there was no association between a-GBMs and U-alb. The U-NAG and U-NAG A were negatively correlated with storage time. The results may suggest that microalbuminuria and enzymuria reported in subjects with ongoing exposure to Hg vapour are reversible in most instances. PMID- 8217846 TI - Mortality experience of employees exposed to 2-mercaptobenzothiazole at a chemical plant in Nitro, West Virginia. AB - Mortality trends for 1059 production workers at a rubber chemicals plant in Nitro, West Virginia were examined to find whether they had increased mortality from cancer associated with exposure to 2-mercaptobenzothiazole (MBT). This chemical and its derivatives are vulcanising agents that have been manufactured at the plant since 1935. Analyses were conducted on MBT exposed employees by cumulative exposure and time since first exposure, and were also stratified by past assignment to p-aminobiphenyl (PAB) related departments; PAB is a potent bladder carcinogen that was used at the plant between 1935 and 1955. There was an excess of bladder cancer in MBT workers who had PAB related assignments (standardised mortality ratio (SMR) = 3200, 95% confidence interval (95% CI) 1286 6593). In employees without a job assignment with exposure to PAB, there were no associations between exposure to MBT and increased rates of most malignant neoplasms. The SMR for bladder cancer was increased based on three deaths (SMR = 455, 95% CI 94-1328), although these results were too few to evaluate trends by cumulative exposure category. The possibility of confounding by PAB for exposures for jobs that covered all areas of the plant for these three cases must be considered in the light of the potency of PAB as a bladder carcinogen. There were no deaths from bladder cancer among MBT workers hired after the end of manufacture and use of PAB, but the expected number of deaths was only 0.03. PMID- 8217847 TI - Bronchial symptoms and respiratory function in workers exposed to methylmethacrylate. AB - This study aimed to investigate the pulmonary effects of methylmethacrylate (MMA) in a group of occupationally exposed workers. In the exposed group 20% had chronic cough compared with 1% in controls. Spirometric values at the beginning of the workshift were similar in both groups, but a mild airways obstruction appeared during the workshift. The maximum expiratory flow when 50% of the forced vital capacity remained to be exhaled (MEF50) and the ratio of MEF50 to maximal expiratory flow (MEF50/MEF) decreased significantly during the workshift among exposed workers v controls (p = 0.04 and 0.01 respectively). Results remained unaffected after adjustment for smoking. Exposure to MMA seems to be responsible for a mild airways obstruction but further study on a larger population would be useful. PMID- 8217848 TI - Effect of smoking on pleural thickening in asbestos workers. AB - It is well known that an interaction exists between smoking and exposure to asbestos in the occurrence of lung cancer, whereas occurrence of malignant mesothelioma has not been related to smoking. In the case of pleural thickening related to asbestos, there is a disagreement in previous studies as to the effect of smoking. This could be because the diagnosis of pleural changes has a subjective element. Taking this into account, in the present work the maximum width of the pleura was used as an index of pleural changes. Study subjects were 134 asbestos workers of a brake manufacturing company who had received medical checks in 1978 and in 1990. The maximum width of the pleura on the chest x ray films of the workers was measured by two examiners who did not know the year of examination or smoking state of the worker. A general linear model was applied to analyse the effects of smoking, the year of examination, age, and duration of exposure to asbestos. The difference between maximum widths measured in 1978 and 1990 suggested chronological progression. The increase in width during the 12 years, however, did not differ significantly between smokers and nonsmokers. This suggests that smoking does not significantly increase pleural thickening in asbestos workers. PMID- 8217849 TI - Radiographic abnormalities and mortality in subjects with exposure to crocidolite. AB - Plain chest radiographs from a one in six random sample of the workforce of the asbestos industry at Wittenoom, Western Australia between 1943 and 1966 have been classified for degree of profusion and pleural thickening by two independent observers according to the 1980 UICC-ILO Classification of Radiographs for the pneumoconioses to clarify the effect of degree of radiological abnormality on survival. A total of 1106 subjects were selected. Each subject's age, cumulative exposure to crocidolite, and time since first exposure were determined from employment records, the results of a survey of airborne concentrations of fibres > 5 mu in length conducted in 1966, and an exposure rating by an industrial hygienist and an ex-manager of the mine and mill at Wittenoom. By the end of 1986 193 subjects had died. Conditional logistic regression was used to model the relative risk of death in five separate case-control analyses in which the outcomes were deaths from: (1) all causes, (2) malignant mesothelioma, (3) lung cancer, (4) asbestosis, and (5) other causes excluding cancer and asbestosis. Up to 20 controls per case were randomly chosen from all men of the same age who were not known to have died before the date of death of the index case. After adjustment for exposure and time since first exposure, there were significant and independent effects of radiographic profusion and pleural thickening on all cause mortality. The effect of profusion was largely a result of the effect on mortality from malignant mesothelioma and asbestosis but not lung cancer. The effect of pleural thickening was greatest on mortality from other causes, mainly ischaemic heart disease. This study has shown that degree of radiographic abnormality has an independent effect on mortality from malignant mesothelioma, asbestosis, and all causes even after allowing for the effects of age, degree of exposure, and time since first exposure. PMID- 8217850 TI - Further evidence of human silica nephrotoxicity in occupationally exposed workers. AB - It has previously been shown that granite workers with heavy exposure to silica had glomerular and proximal tubular dysfunction evidenced by increased urinary excretions of albumin, alpha-1-microglobulin (AMG), and beta-N-acetyl glucosaminidase (NAG). The investigation was replicated in another group of granite workers to further elucidate the exposure effect relation. The urinary excretion of albumin, alpha-1-microglobulin (AMG), beta-2-microglobulin (BMG), and beta-N-acetyl-glucosaminidase (NAG) was determined in two groups of granite workers with low and high exposure to silica. Low molecular weight proteinuria and enzymuria were significantly correlated with duration of exposure in the high but not the low exposure group. These increases were most pronounced in those with 10 or more years of heavy exposure, and in those with radiological evidence of pulmonary fibrosis, particularly those with rounded small opacities denoting classical silicosis. These results provide further evidence that prolonged and heavy exposure to silica is associated with nephrotoxic effects in granite workers. PMID- 8217851 TI - Analyses of the 1990 chest health survey of china clay workers. AB - During 1990 all present and retired china clay workers in the United Kingdom were invited to take part in a chest health survey. A total of 4401 china clay workers participated representing over 70% of current employees and 17% of pensioners. The survey consisted of a chest x ray film, lung function measurements, and a questionnaire on respiratory symptoms and smoking habits. The chest x ray films were read by three readers to the International Labour Office (ILO) 1980 classification. Full details of occupational history for each participant were available and for each employee an estimate of total exposure to china clay dust was derived from representative dust concentrations for each location and job. These were based on measured dust concentrations after 1978 and on estimates before 1978. Analyses of the data were carried out to investigate the relations between exposure, x ray film category, lung function, and respiratory symptoms. The percentage of people with small opacities greater than major x ray film category 1 was 0.8% (lower than in previous studies). Dust concentrations have been reduced in recent years, averaging 1.7 mg m-3 for dryers in 1990 compared with 3.5 mg m-3 in 1978. The lower effect of exposure after 1971, compared with earlier exposure, was confirmed by the analyses. After 1971 the milling of dried china clay (Atritor mills) was found to be the occupation with the highest effect on x ray film category. The relation between total exposure to china clay dust and x ray film category is such that a typical non-smoker worker employed in the most dusty of current occupations may expect to reach the lower limit of category 1 after about 42 years continuous employment in that job at current exposures. Both forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were found (as in other studies) to decline with age, more rapidly for smokers than non-smokers at the rates for FVC of 0.035 l/y and 0.033 l/y, whereas for FEV1 the rates are 0.039 l/y for smokers and 0.034 l/y for non-smokers. Changes in x ray film category are also related to lung function , a change of one major category being equivalent to about six years of aging in its effect on FEV1. PMID- 8217852 TI - Mortality from lung cancer in Ontario uranium miners. AB - Mortality from lung cancer was greater in Ontario uranium miners than in the general male population of Ontario (observed = 152, expected = 67.6, standardised mortality ratio 225, 95% confidence interval 191-264). Part of the excess of lung cancer may be because the proportion of men who are smokers or have smoked is greater in uranium miners than in Ontario men. Smoking does not explain the whole excess. Mortality from lung cancer in Ontario uranium miners is clearly related to exposure to short lived radon progeny. The excess relative risk of lung cancer from the same degree of exposure to short lived radon progeny is greatest five to 14 years after exposure and less subsequently. It is greater in men under the age of 55 years and less in older men. Part of the excess of lung cancer mortality in Ontario uranium miners is probably also due to exposure to arsenic that occurred earlier in gold mines. In Ontario uranium miners, the lung cancer mortality from exposure to arsenic increases as the intensity of exposure to short lived radon progeny increases. This finding is consistent with the hypothesis that the risk of lung cancer from exposure to arsenic is enhanced by exposure to other carcinogens. In Ontario uranium miners, the proportion of lung cancers that are small cell carcinomas is greater than in the general population. The proportion of small cell carcinomas is especially great five to 14 years after exposure to short lived radon progeny and in men who die from lung cancer at younger ages. PMID- 8217853 TI - Longitudinal and cross sectional analyses of exposure to coal mine dust and pulmonary function in new miners. AB - The association between exposure to dust and pulmonary function was studied by longitudinal and cross sectional analyses in a group of United States underground coal miners beginning work in or after 1970. Quantitative estimates of exposure to respirable coal mine dust were derived from air samples taken periodically over the entire study period. The cohort included 977 miners examined both in round 2 (R2) (1972-5) and round 4 (R4) (1985-8) of the National Study of Coal Workers' Pneumoconiosis. Multiple linear regression models were developed for both cross sectional (pulmonary function at R2 and R4) and longitudinal (change in pulmonary function between R2 and R4) analyses with exposure partitioned into pre-R2 and post-R2 periods and controlled for covariates including smoking history. The results indicate a rapid initial (at R2) loss of FVC and FEV1 in association with cumulative exposure of the order of 30 ml per mg/m3-years. Between R2 and R4 (about 13 years) no additional loss of function related to dust exposure was detected although the percentage of predicted FVC and FEV1 did decline over the period. After some 15 years since first exposure (at R4), a statistically significant association of cumulative exposure with FEV1 of about 5.9 ml per mg/m3-years was found. These results indicate a significant non-linear effect of exposure to dust on pulmonary function at dust concentrations present after regulations took effect. The initial responses in both the FVC and FEV1 are consistent with inflammation of the small airways in response to exposure to dust. PMID- 8217854 TI - A study of the health conditions of child workers in a small scale leather industry in Calcutta. AB - Forty male children aged between seven and 14 years, working in small scale leather workshops in a slum locality in Calcutta were studied, along with a control group of 40 non-working male children of the same age group, same locality, and the same socioeconomic class. Three specific health problems- namely, low back and ankle pain, dizziness, and tingling pain in the hands were found in a significantly higher proportion in the working children. For height, weight, nutritional state, and general morbidity pattern, however there were no significant differences between the two groups. Possibly the particular sitting posture of the child workers for long working hours and the chemical nature of the glue and solvents used in this industry were responsible for the manifestations in the working children. PMID- 8217855 TI - Prevalence and risk factors for chronic bronchitis and farmer's lung in French dairy farmers. AB - The prevalence of chronic bronchitis and of clinical farmer's lung was studied in 30 districts of the French Doubs province in relation to individual (age, sex, smoking) and geographical (altitude) factors. 5703 exclusively dairy farmers (response rate 83%) participated in the study by answering a medical questionnaire. Prevalences of chronic bronchitis and clinical farmer's lung were 9.3% and 1.4% respectively. A logistic regression model was used to evaluate risk factors for chronic bronchitis and clinical farmer's lung. A risk of chronic bronchitis was associated with male sex (p < 10(-4)), age (p < 10(-4)), smoker category (p < 10(-4)), and altitude (p < 10(-4)). A risk of clinical farmer's lung was associated with non-smokers (p < 0.05), and linearly with altitude (p < 10(-4)). Also there was a strong positive relation between chronic bronchitis and clinical farmer's lung (odds ratio 19.5 (95% confidence interval 12.1-31.4) after adjustment for confounding variables. The main finding of this study is the highly significant increase of prevalence of the diseases in relation to altitude. PMID- 8217856 TI - Mental retardation and parental occupation: a study on the applicability of job exposure matrices. AB - In a case-referent study on mental retardation and parental occupation, the applicability of job exposure matrices for the identification of risk factors was evaluated. The parents of 306 mentally retarded children (cases) and 322 referents were interviewed about their occupational activities in the pregnancy period. Detailed occupational histories were obtained that were compared with exposures generated by two different job exposure matrices. The agreement between interview and matrices was low: the sensitivity ranged from 17.9% to 32.4% and the percentages of false positive exposures from 66.7% to 96.0%. By means of the interview, significantly increased odds ratios (ORs) were found for exposure of the mother in late pregnancy to radiation (OR = 9.3), mercury (OR = 8.7), organic solvents (OR = 1.7), hair cosmetics and dyes (OR = 3.7), paint (OR = 2.7), hexachlorophene/phenylphenol (OR = 3.1), antibiotics (OR = 2.9), and dust (OR = 2.2) and for working with copying machines (OR = 3.0) or in occupations with poor climatological circumstances and permanent contact with people. The last was confirmed by the British matrix (OR = 1.7). Otherwise, most of the mentioned associations were missed by the job exposure matrices. Therefore, these matrices were not considered to be applicable in this particular study, nor in most other reproductive epidemiological studies in view of their general properties and limitations. PMID- 8217857 TI - Synergistic effects of mineral fibres and cigarette smoke on the production of tumour necrosis factor by alveolar macrophages of rats. AB - The objective of this study was to evaluate the combined effects of mineral fibres and cigarette smoke on the production of tumour necrosis factor (TNF) by alveolar macrophages. Rats were exposed to cigarette smoke in vivo, and production of TNF by alveolar macrophages was measured in the presence of mineral fibres in vitro. For smoke exposure, rats were divided into two groups. Five were exposed to a daily concentration of 10 mg/m3 of cigarette smoke for an eight hour period, and five rats (controls) were not exposed to smoke. Bronchoalveolar lavage was performed after exposure to smoke and the recovered alveolar macrophages were incubated with either chrysotile or ceramic fibres on a microplate for 24 hours. Activity of TNF in the supernatant was determined by the L-929 fibroblast cell bioassay. When alveolar macrophages were not stimulated by mineral fibres, production of TNF by rats exposed to smoke and unexposed rats was essentially the same. When alveolar macrophages were stimulated in vitro by chrysotile or ceramic fibres, production of TNF by alveolar macrophages from rats exposed to smoke was higher than that by alveolar macrophages from unexposed rats. The findings suggest that cigarette smoke and mineral fibres have a synergistic effect on TNF production by alveolar macrophages. PMID- 8217858 TI - Federal funding of medical research. PMID- 8217859 TI - Psychophysiological and behavioral differences as a function of age and Parkinson's disease. AB - Differences related to age and to specific neurological (Parkinsonian) damage were studied by contrasting, respectively, old (mean age 64 years) and young (27 years) subjects (N = 15), and old-normal (N = 15) and old-Parkinsonian (N = 15) subjects. Both behavioral as well as psychophysiological dependent variables were employed. The behavioral measure was performance on a discrimination learning task, while the psychophysiological measures were based on habituation to a repeated tone stimulus and on a Pavlovian differential conditioning preparation. The behavioral task showed predominantly age-related differences, with the young learning faster. Another age-related difference was interpreted as showing a more insight-like learning process in the young. Response-bias (beta) values did not differ between groups. Age-related differences also emerged more clearly than specific-neurological-damage differences in the psychophysiological data. The older subjects manifested markedly less autonomic conditioning, which was probably due to a lowering of reactivity, as well as the emergence of habituation to the (loud-noise) unconditional stimulus. A correlational analysis of discrimination conditioning also yielded age-related differences. Most notably, reactivity played a greater role in conditioning in the old than in the young subjects. The results illustrated how psychophysiological measures can provide information that complements those provided by behavioral measures. PMID- 8217861 TI - The problem of switching in conditional behavior. AB - This article reviews studies of various authors on the phenomenon of "switching," which is observed in both classical and instrumental conditioning and consists in elicitation of different responses to the same conditional stimulus (CS) when it is applied in an environment different than the original one. The different responses include a decrease or an absence of the previously trained conditional response (CR), elicitation of an appetitive response instead a defensive one, or vice versa, as well as elicitation of two different instrumental CRs in the same trial. The studies suggest that, due to the repeated occurrence of CS in the same environment (E), also called "situation" or "context," associations are formed between CS and E. Consequently, the CR is elicited to a compound CS+E rather than to CS alone. When the CS is applied alone in a different E than the original one, the previously formed associations are inactive and the CR cannot be elicited; this leads to switching. Studies also suggest that E plays a dominant role in conditioning compared with that of CS alone, which often appears to be only a trigger for eliciting the response. However, CS tested in a different E may still produce some components of the previously acquired CR, such as a general fear behavior to an originally defensive CS or an approach behavior to an originally alimentary CS. The environmental stimuli can be considered the "determining" stimuli that determine the kind of reaction to be elicited, or "tonic" stimuli that increase the tonus in the brain but do not elicit the CR. The "determining" or "tonic" stimuli do not seem to be a special class of stimuli. Instead, they are stimuli that initially can produce the CR (e.g., intertrial CRs), but by being not reinforced they become partly inhibited; nevertheless, due to associations with the reinforcement, they still can produce some excitement related to it, thus facilitating the CR. PMID- 8217860 TI - Cortical control of sinus arrhythmia in man studied by spectral analysis. AB - Eighteen healthy male volunteers, 21-26 years old, participated in a study intended to detect cortical control of beat-to-beat heart rate variability independent of the effects on breathing and mean heart rate. They were tested while seated and standing relaxed (baseline), and while performing tasks requiring concentrated attention while sitting. The mental concentration elicited a typical cardiorespiratory response manifested by moderate acceleration and shallowing of respiration with a small increase of mean heart rate (HR), a pattern already widely acknowledged as typically associated with concentration. With the aid of a variable tone delivered to the ear as a guide, the subjects were trained to breathe at the same rate without concentrating in order to test the influence of respiration on the concentration pattern. ECG, thermistor pneumogram and ear-lobe photo-plethysmogram were recorded and data reduction was performed on 3 minute or 1 minute data sequences selected for the best steady state. Statistical treatment was limited to a subgroup of 10 subjects in whom there was no overlapping of the spectra of respiratory and Traube-Hering-Mayer sinus arrhythmia (RSA and THM-SA, respectively). Mental concentration elicited significant depression of both RSA and THM-SA even if the respiratory parameters were kept constant. PMID- 8217862 TI - Two-component arterial blood pressure conditional response in rat. AB - The objective of these experiments was to quantify the pattern of change in arterial blood pressure (BP) during a discriminative aversive classical conditioning paradigm in rat using a new "high resolution" computer analysis. Sprague-Dawley rats (n = 5) were restrained in a soft, conical cloth pouch and conditioned using a 6 sec. pulsed tone (CS+) followed by a 0.5 sec. tail shock; a steady tone, never followed by shock, served as a CS-. BP peaked at 16.4 +/- 6.5 mm Hg (mean +/- SD) above control at 1.5 +/- 0.1 sec. after onset of CS+. This "first component" ("C1") also occurred during CS- (12.1 +/- 3.8 mm Hg), although the magnitudes of the two were significantly (p < 0.05) different. Another group of rats (n = 8) was treated identically except the tones were 15 seconds long. The conditional BP response consisted of two components. C1 was reminiscent of that seen using the short tone: for CS+ a peak of 13.6 +/- 5.6 mm Hg at 1.5 sec. or, for CS-, of 10.0 +/- 4.3 at 1.3 sec. (p < 0.05). In CS+ trials BP peaked again ("C2," 7.4 +/- 2.5 mm Hg) at 8.3 +/- 1.2 sec. There was no statistically significant C2 for CS- trials, clearly demonstrating discrimination between tones. The unconditional BP response in both groups consisted of two large, closely spaced peaks in BP. Respiration was recorded in 3 additional rats. After shock delivery these subjects often showed a sudden shift between (1) a regular respiratory pattern with moderate chest excursion and (2) apneic episodes interspersed with single, deep breaths. This latter pattern was associated with large, low frequency fluctuations in BP. Continued development of the rat conditioning paradigm is especially warranted because of the ability to record sympathetic nerve activity in intact, awake subjects and the large number of readily available genetic strains, which model human pathological states. PMID- 8217863 TI - Psychotraumatology: a two-factor formulation of posttraumatic stress. AB - Other than the "sudden death" phenomenon, posttraumatic stress represents the most severe and incapacitating form of human stress (Everly, 1989). Posttraumatic stress is directly associated with three DSM-III-R, Axis I disorders: Posttraumatic Stress Disorder (PTSD), Multiple Personality Disorder, and Brief Reactive Psychosis (APA, 1987). It is similarly associated with the Axis II personality disorder Borderline Personality Disorder (Herman and van der Kolk, 1987). Posttraumatic stress may be indirectly related to various forms of mood disorders, substance abuse syndromes, and phobic disorders. Regarding the prevalence of posttraumatic stress, Helzer et al. (1987) found the lifetime prevalence of PTSD at around 1% in the general population. Breslau et al. (1991) found the prevalence of PTSD to be 9% in a cohort of young adults in an urban setting. They further found a prevalence of 24% in young adults who had been exposed to traumatic events. Norman and Getek (1988) have estimated that nearly one-half of all patients admitted to urban trauma centers are likely to suffer from PTSD in addition to their physical traumatization, while another 31% may suffer from a milder variant of posttraumatic stress. These data argue compellingly for the potential severity of the threat that posttraumatic stress poses to society. Yet, no one clear-cut therapy for posttraumatic stress has emerged, nor has a generally agreed-upon phenomenology emerged upon which to base such a therapy. The purpose of this paper is to present a comprehensive formulation of posttraumatic stress based upon an integration of biological and psychological evidence. PMID- 8217864 TI - Coronary blood flow in dogs: effect of person. AB - Experiments on dogs with electromagnetic flow probes implanted around a coronary artery and the ascending aorta indicate that the entry of a person into the experimental chamber can cause a remarkable increase in coronary blood flow. Heart rate usually increases considerably, blood pressure increases only slightly, while aortic blood flow increases at variable times before and after coronary blood flow. It is not yet clear whether these cardiovascular effects are due purely to "effect of person" or to conditioning, with the person as the signal for the momentary coronary occlusion (which the person subsequently accomplishes by manually closing a snare). PMID- 8217865 TI - Evaluation of a method for simultaneous quantification of codeine, dihydrocodeine, morphine, and 6-monoacetylmorphine in serum, blood, and postmortem blood. AB - A solid-phase extraction and gas chromatographic-mass spectrometric method for the simultaneous determination of codeine, dihydrocodeine, morphine, and 6 monoacetylmorphine in serum, blood or postmortem blood is described. The extraction technique allows the determination of free or total morphine (morphine plus morphine glucuronide). Experiments with spiked blood samples resulted in recoveries of 96.4% +/- 4.2% for codeine, 95.8% +/- 5.1% for dihydrocodeine, 90.3% +/- 7.8% for 6-monoacetylmorphine and 92.5% +/- 8.1% for morphine. Excellent linearity was obtained over the range 1-1500 ng/mL. The detection limit for all analytes is less than 1 ng/mL. PMID- 8217866 TI - Sudden fatal or non-operable bleeding from ruptured intracranial aneurysm. Evaluation by post-mortem angiography with vulcanising contrast medium. AB - A series of medicolegal autopsies on 76 patients with fatal outcome following haemorrhage from ruptured intracranial aneurysm comprised 63 surgical patients and 13 non-surgical patients (M:F 6:7 mean age 44.0 +/- 18.1 years), all of the latter with sudden fatal course or dramatically poor clinical condition on admission. The medicolegal autopsy was performed because of the sudden and unexpected nature of the death, or to exclude surgical malpractice. Postmortem angiography with vulcanising contrast medium disclosed intraventricular haemorrhage (IVH) in 12 (92%) of the non-surgical fatalities, whereas IVH was thus characterized in only 17 (27%) of the 63 fatalities who had undergone neurosurgery (P < 0.0001). The most common type of haemorrhage among surgical cases was, instead, subarachnoid haemorrhage (SAH) (P < 0.05). In 35 of the 76 cases (46%), casts of cerebral arteries demonstrated vasospasm-induced segmental narrowings, but such narrowings were no more frequent among the non-surgical cases than in surgical cases, nor did these narrowings correlate with IVH. In non surgical patients, the haemorrhage most commonly originated from a ruptured aneurysm of the middle cerebral artery (P < 0.05), an event more frequently associated with the presence of IVH (P < 0.05) than without it. The results indicate that the main cause for sudden and unexpected death or rapidly developed poor non-operable clinical condition of patients with ruptured intracranial aneurysm is an IVH from a middle cerebral artery aneurysm, complicated in many cases by cerebral artery vasospasm. PMID- 8217867 TI - Terminal ballistics of the 7.62 mm NATO bullet. Autopsy findings. AB - The 7.62 mm x 51 military rifle bullet (7.62 mm NATO) as manufactured in Denmark, and in some other countries as well, has been claimed to fragment when fired at ranges encountered in forensic practice. All autopsied cases of death due to this bullet in Denmark since 1975 were investigated by studying autopsy reports and the bullets retrieved by the police. With one exception, all bullets that were found in, or known to have passed through the body, had fragmented. This behaviour is assumed to be due to a lack of strength in the jacket causing it to break at the cannelure when hitting the target at high velocity. The fragments will increase the already sizeable lesions and may leave the body through several separate exit wounds, presenting problems both for the surgeon treating survivors and for the forensic scientists when defining the direction of the shot. The legality of this and similar bullets in view of the Hague Declaration of 1899 may be questioned, and we feel that the bullet should be redesigned. A programme to this end has been initiated by the Danish state owned ammunition factory. PMID- 8217868 TI - DNA typing of urine samples following several years of storage. AB - The possibility of typing DNA polymorphisms on urine samples was investigated in a controlled storage experiment and for samples that were 1-7 years old. Female urine samples showed a higher amount of epithelial cells and therefore a higher DNA yield. Employing the polymerase chain reaction, specific amplification results were achieved for all samples over a 6 month storage period. The microscopical examination of the samples revealed not only differing degrees of contamination with bacteria, yeasts and fungi, but also the presence of still intact epithelial cells. Only 20% of the male samples and 32% of the female samples yielded specific amplification results. By separating the human cells from the contaminating organisms prior to DNA extraction, the number of successfully typed samples could be improved to 35% of the male and 77% of the female samples. This result confirms that excess amounts of co-extracted non human DNA can inhibit the specific amplification of human target sequences. PMID- 8217869 TI - DNA typing of debris from fingernails. AB - In 3 series paired volunteers were asked to gently scratch each other with the fingernails to produce superficial abrasions only of the stratum corneum. In a 4th series scratch marks were produced in the skin of cadavers but additionally including the deeper epidermal layers. Debris was removed using a thorough technique in series 1 and 2 and a careful technique in series 3. After DNA extraction, the debris was typed using the STR systems HUMACTBP2 (SE33), HUMTH01 (TC11) and HUMVWFA31 (VWA). In the material obtained from series 1 (i.e. scratching with no prior cleaning of the nails) and series 2 (i.e. cleaning of the nails prior to the experiment) the debris was removed with a sharp instrument and only the DNA pattern of the person who carried out the scratching could be detected. In the 3rd series extraneous material was removed very carefully from under the fingernails to avoid contamination with DNA from the nails. In 71% of these cases DNA patterns of the person who had been scratched or mixed DNA patterns of both persons could be detected. In the experiments with postmortem skin the DNA pattern of the cadaver could be detected in all cases. These results show that in crime cases where the perpetrator has been scratched by the victim, sufficient material can be obtained from under the fingernails for DNA typing if removal of the particles is carried out with sufficient care. PMID- 8217870 TI - The application of mitochondrial DNA typing to the study of white Caucasian genetic identification. AB - Mitochondrial DNA (mtDNA) from 100 unrelated British White Caucasians was extracted, amplified and directly sequenced. Sequences of approximately 800 nucleotides were obtained from 2 hypervariable segments within the non-coding region of the mitochondrial genome. A total of 91 different sequences were observed with an average nucleotide diversity of 1.1%. The most diverse pair of sequences differed at 3.6% of their nucleotide (nt) sites. Comparison to a consensus reference sequence showed that each region was polymorphic to a similar extent. Different methods of genetic analysis were used to examine the variation in each region, including pairwise comparisons, which demonstrated that although the data did not fit a Poisson distribution, the fit was closer to a Negative Binomial distribution. PMID- 8217871 TI - Photometric measurement of color changes in livor mortis as a function of pressure and time. Development of a computer-aided system for measuring pressure induced blanching of livor mortis to estimate time of death. AB - Until now, blanching of livor mortis in estimating time of death has generally been assessed based on subjective impressions, i.e. on whether blanching is visible after the application of pressure. We have developed a measuring system that uses digital processing to objectify the relationship between the pressure applied and blanching of postmortem lividity. The pressure is electronically registered by a strain gauge. At predefined levels (10, 20, 30, up to 100 N) the software triggers a color measurement by a commercially available tristimulus colorimeter. All parameters are measured in a single procedure and routed to the computer through a data interface. The pressure-induced color changes in the livor mortis are evaluated according to the L*, a*, b* system (CIE-LAB according to DIN 5033, DIN 6174), which closely approximates the physiology of sight. An additional color spacing formula (delta E) allows analysis of color changes irrespective of the basic skin tone. Initial measurements on cadavers showed that application of increasing pressure produced regular courses of color changes in livor mortis. PMID- 8217872 TI - Sudden death due to cardiac sarcoidosis in a case of suspected homicide. AB - In a case of suspected homicide death due to natural causes--cardiac death (SCD)- was found at autopsy. Despite an extensive replacement of myocardial tissue by sarcoid granulomata there was no history of cardiac dysfunction or preceding symptoms. The transmurally infiltrating granulomata and the concomitant fibrosis were predominantly confluent. They occupied vast areas within the interventricular septum and the adjacent posterior wall of the left ventricle. The only other organs involved were mediastinal lymph nodes, which appeared macroscopically normal. PMID- 8217873 TI - Oxysterol-induced cell death in human leukemic T-cells correlates with oxysterol binding protein occupancy and is independent of glucocorticoid-induced apoptosis. AB - In eukaryotic cells oxysterols inhibit cholesterol biosynthesis and cell growth. A potent oxysterol, 25-hydroxycholesterol, was used to investigate the biological effects of oxysterols on three clonal lines of either glucocorticoid-sensitive or -resistant CEM cells, human leukemic T-lymphocytes. In addition, the glucocorticoid sensitivity of an oxysterol-resistant CEM cell line was tested. Oxysterols blocked growth and caused the lysis of cells regardless of their glucocorticoid response. All cells studied herein possessed an oxysterol binding protein with high affinity for 25-hydroxycholesterol. For all clones grown in serum-free medium, the half-maximal cytolytic concentration of 25 hydroxycholesterol (20-40 nM) correlated with its affinity (Kd = approximately 31 nM) for this oxysterol binding protein. Both cholesterol and mevalonate reversed 25-hydroxycholesterol cytotoxicity; 3-6 microM cholesterol or 0.1 mM mevalonate decreased 60 nM 25-hydroxycholesterol cytotoxicity by 50%. This cholesterol or mevalonate reversal appeared possible even after several days of 60 nM oxysterol treatment. The protective effect of cholesterol could be overcome by increasing 25-hydroxycholesterol concentrations. Cholesterol and mevalonate did not prevent glucocorticoid-mediated lymphocytolysis. Furthermore, the oxysterol-resistant line was sensitive to dexamethasone lysis. These data support the hypothesis that oxysterols and glucocorticoids act independently to block the growth of human leukemic lymphoblasts. PMID- 8217874 TI - Regulation of anterior pituitary gonadotropin subunit mRNA levels during the preovulatory gonadotropin surge: a physiological role of progesterone in regulating LH-beta and FSH-beta mRNA levels. AB - In a previous study we demonstrated that in the ovariectomized estrogen-primed immature rat, progesterone induced a gonadotropin surge while the gonadotropin mRNA subunit levels were either suppressed or unaltered. This observation has now been confirmed using more frequent time points. Progesterone administered at 0900 h was found to suppress LH-beta mRNA levels at 1300, 1400, and 0800 h the next day, with no subsequent effects at 1000, 1200 or 1600 h. FSH-beta mRNA levels were unaffected by progesterone except for a slight elevation at 1400 h and a suppression at 0800 h. Progesterone was either suppressive or had no effect on alpha mRNA levels. Since elevations in LH-beta and FSH-beta mRNA levels were observed in the cycling rat, the observed differences in the ovariectomized estrogen-primed rat could be due to a higher basal synthesis occurring due to ovariectomy. This was indeed the case because LH-beta and FSH-beta mRNA levels were 3.7- and 42.7-fold higher in such animals as compared to intact estrogen primed rats. In contrast to the ovariectomized estrogen-primed rats, in intact estrogen-primed rats LH-beta mRNA levels were increased at 1000 h and FSH-beta mRNA levels were increased at 1000, 1200 and 1300 h after the administration of progesterone. In pregnant mare's serum gonadotropin-primed immature rats, LH beta, FSH-beta and alpha-subunit mRNA levels were significantly elevated at 1800 and 2000 h, paralleling the serum LH and FSH surge. The progesterone antagonist RU486 (0.2 and 1.0 mg) significantly reduced serum LH and FSH levels at 2000 h. The lower dose reduced LH-beta and alpha-subunit mRNA levels at 2000 h and FSH beta mRNA levels at 1800 h. The higher dose caused an increase in LH-beta mRNA levels at 1200 and 1800 h and a decrease in FSH-beta mRNA levels at 1800 and 2000 h. In conclusion, the present study provides evidence that preovulatory progesterone plays an important role in the increase in FSH-beta mRNA levels as well as the release of LH and FSH during the normal preovulatory gonadotropin surge. This relationship appears to be dependent on the ongoing rate of synthesis because this does not occur in the ovariectomized estrogen-primed rat in which synthesis is at a high basal level. Furthermore, the correlation with FSH appears to be tighter as compared to LH. PMID- 8217875 TI - Non-consensus progesterone response elements mediate the progesterone-regulated endometrial expression of the uteroferrin gene. AB - A 2.0 kilobase-pair (kb) fragment encompassing the promoter and 5' flanking region of the uteroferrin (UF) gene was previously demonstrated to confer progesterone (P) responsiveness to chimeric UF gene promoter-reporter gene constructs when transfected in endometrial cells. In the present study, transient transfection experiments with the chloramphenicol acetyltransferase reporter gene linked to the sequentially deleted UF gene 5' flanking region and to genomic fragments within this region subcloned into the heterologous SV40 promoter were used to define the progesterone-responsive elements (PRE). The identified PREs are located distal to the promoter in the region between -1754 to -1601 bp and 893 to -678 bp of the UF gene and exhibit only limited similarities to the half sites of the consensus palindromic PRE. The non-consensus PREs bind the progesterone receptor (PR) and independently exhibit P-dependent enhancer activities within the context of homologous and heterologous promoters in endometrial and placental cell lines. The unique features of these functional PREs suggest that formation of the P-PR complex with its cognate sequences upstream of the UF gene may be less dependent on the sequence per se but may require the binding of nuclear factors proximal to the PRE to stabilize PRE-PRE interactions. PMID- 8217876 TI - Inhibition of estrogen stimulated mitogenesis by 3-phenylacetylamino-2,6 piperidinedione and its para-hydroxy analog. AB - 3-Phenylactetylamino-2,6-piperidinedione (A10) inhibited estradiol stimulated cell growth in the MCF-7 (E3) human breast tumor cell line in vivo and in vitro. While high concentrations of A10 were needed to inhibit cell proliferation (IC50 = 3 x 10(-3) M in vitro), the compound demonstrated little toxicity. The effect appeared specific since a hydrolysis product of A10, phenylacetylglutamine, demonstrated no growth inhibitory activity at similar concentrations in MCF-7 (E3) cells in vitro. A computer designed analog, p-hydroxy A10, was more potent than A10 in inhibiting activity in MCF-7 (E3) cells in vitro. The IC50 for p hydroxy A10 was 7 x 10(-6) M which was comparable to that of the antiestrogen, tamoxifen (IC50 1 x 10(-7) M). All three compounds caused a decline in estrogen receptor levels in a dose-dependent fashion. A10 also inhibited estradiol induction of progesterone receptors. Examination of protein kinase activity following an acute exposure to a 10(-11) M growth stimulatory dose of estradiol revealed a 168% increase in protein kinase activity over that of untreated control cells. A10 in a dose-responsive fashion inhibited the estradiol stimulated increase in protein kinase activity. The protein kinase activity was also inhibited by p-hydroxy A10. These activities of A10 and p-hydroxy A10 coupled with the low toxicity and novelty of the basic A10 structure provide an exciting possibility of developing a new class of clinically useful antineoplastic drugs with minimal side effects. PMID- 8217877 TI - Relationship of HSP27 and oestrogen receptor in hormone sensitive and insensitive cell lines. AB - A 27 kDa heat shock (HSP27) has been analysed by immunoassay and immunoblotting in oestradiol sensitive and insensitive cells. Oestradiol growth responsive MCF7 and T47D human breast cancer cells and growth unresponsive variants derived therefrom have unaltered levels of HSP27 as well as retaining their oestradiol receptor phenotype. MCF7 cells induced to become doxorubicin resistant in culture lose both HSP27 and oestradiol receptor. Thus, in these three pairs of cells, HSP27 content parallels oestradiol receptor (ER). Analysis of a range of ER positive and negative human cell lines supports the positive relationship between HSP27 and ER. This included six ER positive and two ER negative breast tumour lines, one ER positive and one ER negative endometrial tumour cell line and seven ER negative human lines from other sites. One ER negative osteosarcoma line (HTB96) had appreciable levels of HSP27 that were unaffected after stable transfunction with an ER cDNA. Heat shock increases HSP27 levels in some but not all cell lines tested, the effect being inversely proportional to the basal (37 degrees C) content. In a mouse mammary tumour cell line, loss of androgen sensitivity was accompanied by loss of HSP27. Loss of HSP27 occurred in MCF7 cells made drug resistant to Novatrone, vincristine and etoposide as well as doxorubicin; no detectable change was seen in cells made resistant by 5 fluorouracil or X-irradiation. In ER positive ZR75 human breast tumour cells and in both ER negative and positive variants of the HTB96 human osteosarcoma line, the intracellular distribution of HSP27 was analysed. Over 96% of the HSP27 was in the cytosol fraction and the distribution was unaffected by incubation with oestradiol. HSP27 has been discussed in the literature under three different names p29, p24 and HSP27. The data presented in this paper are reviewed in the context of the previous data. It is concluded that there is a good but not absolute correlation between the presence of ER and high amounts of HSP27 but that low amounts of HSP27 are present in many ER negative cells. The correlations between HSP27 and drug resistance are more complex. PMID- 8217878 TI - Identification and characterization of cytosolic sulfotransferase activities in MCF-7 human breast carcinoma cells. AB - MCF-7 human mammary carcinoma cells have been reported to possess beta-estradiol and dehydroepiandrosterone sulfotransferase activities. These steroid sulfotransferase activities may be important in the metabolism and activity of different steroids in these cells. This report describes and characterizes both the enzymatic activity of three cytosolic sulfotransferases found in MCF-7 cells and the corresponding immunoblot analysis of these enzymes with specific anti sulfotransferase antibodies. Two cytosolic sulfotransferases have been purified and characterized from human tissues which are capable of sulfating estrogens. These are the phenol-sulfating form of phenol sulfotransferase (P-PST) and the hydroxysteroid sulfotransferase, dehydroepiandrosterone sulfotransferase (DHEA ST). The results of this study show that P-PST is the major cytosolic sulfotransferase found in MCF-7 cytosol and is responsible for most of the beta estradiol sulfation in these cells. Although DHEA-ST activity was found in MCF-7 cytosol, this activity was only about 3% of the P-PST activity. Immunoblot analysis of MCF-7 cytosol detected both P-PST and lower levels of the monoamine sulfating form of PST; however DHEA-ST could not be detected apparently because of low levels of expression. Human liver P-PST was expressed in Cos-7 Green monkey kidney fibroblasts and the ability of the cloned enzyme to sulfate beta estradiol was investigated. This study indicates that P-PST is the prevalent cytosolic sulfotransferase in MCF-7 cytosol and is responsible for the majority of beta-estradiol sulfation in these cells. PMID- 8217879 TI - In vitro and in vivo inhibition of nuclear type II estrogen binding sites in the dorsolateral prostate of noble rats. AB - Competition analyses with a number of known bioflavonoids and related compounds revealed that three of them competed effectively for type II [3H]estradiol- 17 beta ([3H]E2) binding sites (type II sites) in the nuclei of rat dorsolateral prostate (DLP). Amongst the bioflavonoids tested, quercetin was the most effect, exhibiting approx. a 50% inhibition at 3000-fold molar excess concentration. In contrast, rutin and hesperitin were both not effective. Methyl p hydroxyphenyllactate (MeHPLA), a suspected "endogenous" ligand for uterine type II sites [1; J. Biol. Chem. 263, 1988, 7203-7210], competed as well as estradiol 17 beta (E2) for prostatic type II sites (50% inhibition at 30-fold molar excess), whereas its demethylated product, HPLA, did not. 4,4'Dihydroxybenzylidene acetophenone, an esterase-stable MeHPLA analog, was also found to be a good competitor, exhibiting a 50% inhibition at 100-fold molar excess concentration. In a preliminary in vivo study, quercetin, administered either orally or subcutaneously, was found to be effective in preventing a joint testosterone (T) and E2 treatment-induced elevation of type II sites in rat DLP. Quercetin treatments also caused a small but significant reduction (17-18%) in DLP relative gland weights (gland wt/body wt) in T + E2-treated animals. Taken together, these data suggest that bioflavonoids and related compounds may influence prostatic function via interactions with prostatic type II sites. PMID- 8217880 TI - Evidence that human placenta is a site of sex hormone-binding globulin gene expression. AB - The presence of an androgen-binding component in placenta was investigated in vitro using a tissue culture system of human placental explants. Explants of trophoblastic tissue from normal term placentas were kept in culture under appropriate conditions for at least 48 h in a serum-free medium. The existence of an androgen-binding protein was explored by binding assays, immunohistochemistry studies and Northern blot analyses of placental mRNA. Steady-state polyacrylamide gel electrophoresis and Scatchard plot analyses revealed the presence of a high affinity specific binding component for 5 alpha-dihydrotestosterone in cultured placenta. Immunohistochemical studies performed on intact placenta and on Percoll gradient purified trophoblastic cells demonstrated the presence of specific immunoreactivity in the cytoplasm of syncytial cells. Northern blot analyses of placental mRNA showed a single hybridizable 32P-labeled human sex hormone-binding globulin (SHBG) cDNA band of approx. 1.6 kb which was identical in size to that obtained with liver mRNA. The results strongly suggest the placenta as an origin of SHBG and point out this tissue as an additional site of SHBG synthesis during pregnancy. PMID- 8217881 TI - Enzyme immunoassay for nomegestrol acetate in human plasma. AB - Currently available chromatographic assays of the progestative drug nomegestrol acetate in human plasma are not suitable for monitoring drug kinetics more than 24 h after clinical dosage. A specific and sensitive enzyme immunoassay was therefore developed. A 3(O-carboxymethyl)oxime derivative of nomegestrol acetate was synthesized and coupled to bovine serum albumin in order to raise polyclonal antibodies in rabbits. The enzymatic tracer was obtained by coupling the 3(O carboxymethyl)oxime derivative to acetylcholinesterase (E.C.3.1.1.7.). HPLC fractionation of human plasma samples followed by enzyme immunoassay revealed the presence of cross-reacting metabolites. An automated procedure of metabolite separation was developed using silica bonded with diol groups (Diol Bakerbond column). This procedure ensured assay specificity. The quantification limit in human plasma was 0.1 ng/ml. Mean repeatability (intra-assay variation) and reproducibility (inter-assay variation) were 9 and 15%, respectively. The enzyme immunoassay allowed monitoring of the kinetics of nomegestrol acetate 144 h after oral administration of a single 5 mg dose. Values for human samples were in excellent agreement with those assayable by HPLC followed by u.v. detection. PMID- 8217882 TI - Inhibition of steroid 17 alpha-hydroxylase and C17,20-lyase in the human testis by epitestosterone. AB - Epitestosterone (17 alpha-hydroxy-4-androsten-3-one) inhibited competitively 17 alpha-hydroxylation of pregnenolone and subsequent C17,20-side chain cleavage of resulting 17 alpha-hydroxypregnenolone using microsomal preparations from the human testis. The inhibition constants for 17 alpha-hydroxylase and C17,20-lyase with 5-ene-precursors of C21-steroids were 96 and 12.4 mumol/l, respectively. PMID- 8217883 TI - 14 Ingredients of "the huddle" in the practice of pediatric dentistry. AB - One of the hardest aspects of running the pediatric dental practice is managing stress among staff members. Successful management in pediatric dentistry is about solving and avoiding problems whenever possible. The huddle, a formal but brief meeting among specified staff members, is one tool that can heighten your team's level of enthusiasm, involvement, and teamwork. It will decrease stress and pressure, while increasing communication among those involved. By including key elements in your huddles, you can use this tool to personalize your treatment objectives and increase quality and service to your patients. PMID- 8217884 TI - Congenitally missing teeth: an alternative approach for space closure. AB - While closing the large bilateral spaces caused by either the extraction of molar teeth or the congenitally absence of premolar in the lower arch, the important point is to move the teeth bodily and avoid tipping as much as possible. For this purpose an alternative orthodontic treatment approach can be the use of Lingual Functional Appliance which mesially moves the mandibular molar teeth bodily and also shortens the fixed orthodontic treatment time. PMID- 8217885 TI - Cephalometric changes in a patient with ectodermal dysplasia after placement of dentures. AB - The purpose of this article is to analyze the changes observed in a three-year old boy affected of ectodermal dysplasia after the placement of complete dentures. Esthetic, functional as well as cephalometric changes are discussed. PMID- 8217886 TI - Direct bonded space maintainers. AB - The aim of this study was to evaluate clinically a bonded space maintainer, which would reduce chair-side time and cost. Sixty appliances were fabricated from 0.7 mm stainless steel round wire and bonded using light-cured composite to the two teeth adjacent to the site of extraction of a posterior primary tooth. Twenty males and sixteen females (age range 5-9-years-old) were selected from the Pedodontic clinic of the State University of Rio de Janeiro. The sixty space maintainers were divided into two groups according to the site in which they were placed: a) absent first primary molar and b) absent second primary molar. Impressions and study models were obtained prior to and 6 months after bonding the appliances. During this period only 8.3% of failures were observed, most of them from occlusal or facial trauma. Student t-test did not show statistically significant alterations in the sizes of the maintained spaces during the trial period. PMID- 8217887 TI - Fluoride uptake by enamel in vitro following application of various topical fluoride preparations. AB - Two conventional topical fluoride preparations; APF and neutral 2% NaF gel and two fluoride varnishes; Duraphat and Fluor Protector, were applied to 60 permanent and 20 primary teeth. The teeth were halved to provide test and control groups, and the fluoride uptake was measured using a micro acid etch technique, after 30 seconds and 60 seconds etching periods. All topical fluoride preparations in our study caused some fluoride uptake in permanent and primary tooth enamel compared to the control groups. Duraphat and APF were found to be more effective than the other agents. PMID- 8217888 TI - The sedative effect of intranasal midazolam administration in the dental treatment of patients with mental disabilities. Part 1. The effect of a 0.2 mg/kg dose. AB - The purpose of this study was to determine the sedative effect of a 0.2 mg/kg dose of midazolam, administered intranasally, prior to performing various restorative dental procedures on a group of mentally disabled patients under local anesthesia and nitrous oxide/oxygen analgesia. Twenty-one patients, aged 4 to 21 years, all of whom had previously exhibited highly combative and resistant behavior toward dental treatment under local anesthesia, were sedated with 0.2 mg/kg midazolam. Only patients assessed as ASA anesthesia status I or II were admitted to the study. After administering the midazolam, each patient was allowed to rest before initiating the dental procedures. Behavioral patterns during the various procedures were rated on a behavioral rating scale of 1-7. Each patient served as his or her own control, comparing behavior with or without intranasal midazolam. The results showed a marked improvement in behavioral patterns after administration of intranasal midazolam. Ratings on a scale of 1-7 were noted as "markedly effective" and "effective" for 69.2% of those patients who received infiltration injection anesthesia, 93.8% under rubber dam, 76.2% during cavity preparation, 84.2% for restoration placement and 87.5% during pulpotomy procedures. The majority of patients were discharged within 150 minutes of intranasal instillation. Further studies are indicated to ascertain the most appropriate dose of intranasally administered midazolam. PMID- 8217889 TI - Oral-facial characteristics of circumscribed scleroderma: case report. AB - Scleroderma is a rare disorder of unknown etiology. Circumscribed scleroderma is a localized focal form. It may present as well defined elevated or depressed white or yellowish patches termed "morphea," or linear bands made up of a furrow with elevated ridges on the margins described as "coup de sabre." The oral-facial characteristics of circumscribed scleroderma in a ten year old afflicted female are described in detail. PMID- 8217890 TI - The CHARGE association: report of two cases. AB - Although many reports of the CHARGE association appear in the literature, the dental findings were never discussed before. In this report of two cases, both patients present with delayed eruption of the permanent teeth and a remarkable similarity of the eruption pattern of the mandibular teeth. One lower permanent central incisor is congenitally missing, while the other is malformed. The lower permanent laterals of JM have erupted lingually and interfere with his speech and function of the tongue. Mandibular retrognathism is present. TM had a V-shaped constricted upper arch, which was expanded in a first phase of orthodontic intervention. Fixed appliances are the future considerations for the correction of the malocclusion. PMID- 8217891 TI - Incontinentia pigmenti (Bloch-Sulzberger syndrome): a case report. AB - A syndrome--incontinentia pigmenti--of probable genetic etiology, is discussed and a new case report presented. The syndrome presents systemic and dental manifestations, which are separate although similar to those found in other disease entities, i.e., congenital syphilis, hereditary ectodermal dysplasia. PMID- 8217892 TI - Teaching kindergarten and elementary school children dental health: a practical presentation. AB - A simple lesson of dental health addressed to children of kindergarten and first grade is presented in a step by step manner. The entire presentation is structured to take less than 30 minutes and minimum teaching aides are required. The terms taught include: plaque, gum, crown, root, dentin, enamel, germ, silver and white fillings and fluoride. The children at the end of the presentation should understand the importance of teeth, how to properly care for their teeth and how cavities form and may be avoided. PMID- 8217893 TI - Augmentative communication for the non-speaking child. AB - In this article, the term non-speaking will be used to refer to those individuals who have limited or no functional speech because of severe physical impairment, neuromuscular or cognitive deficit and whose communication impairment is not due primarily to a hearing problem. Augmentative communication has developed in order to compensate for impairments and disabilities of the non-speaking individual. It is all communication that supplements speech. Pediatric dental patients who may benefit from augmentative communication systems include those with cerebral palsy, multihandicaps, severe mental retardation and autism. The communication board is given as an example of an augmentative communication system. It is a visual display which can use symbols, pictures, letters and words. It allows the non-speaking child to communicate either by listener-assisted scanning or pointing directly to the symbol or word with their hand or eye-gaze, or with an aid such as a pointer or light. A communication board for use in the pediatric dental setting is described. The pediatric dentist should consult with the speech language pathologist, family/caretaker, special educator/teacher, and health care members when deciding on communication systems for the non-speaking child in the dental setting. Augmentative communication systems need to be individualized for each non-speaking child. The systems need constant evaluation and updating also as the child develops. The ultimate aim of augmentative communication is to help the non-speaking child to have a more active and fulfilling role in everyday life. PMID- 8217894 TI - The clinical significance of the biological phenotype of HIV. PMID- 8217895 TI - New developments in the treatment of cryptococcal disease in AIDS. PMID- 8217896 TI - Natural history and therapy of hepatitis B and C in patients with HIV disease. PMID- 8217897 TI - HIV-associated lymphoma. PMID- 8217898 TI - Treatment of HIV disease in 1993/1994. PMID- 8217899 TI - Counseling and medical evaluation of HTLV-I- and HTLV-II-infected patients. PMID- 8217900 TI - Vaccines directed against HIV: preventive and therapeutic strategies. AB - Vaccine therapy studies in HIV-seropositive volunteers over the next year should provide additional insights into whether different vaccine viral strains (LAI, IIIB, MN, SF2), different protein sources (whole virus particles, recombinant protein, peptides), different expression systems (baculovirus, mammalian), or different adjuvants (incomplete Freund's, MTP-PE, MF59, alum) generate significantly different immune responses at the cellular and humoral level. In addition, differences in the ability of each vaccine to induce humoral immune responses to epitopes in the constant regions vs. variable regions, contiguous or noncontiguous "conformational" epitopes, with high vs. low antibody affinity can be evaluated. The roles of antibody-dependent cellular cytotoxicity (ADCC), cellular recognition, nonspecific natural killing, and MHC-restricted cytotoxicity can also be explored. To date, the majority of the immunogens have proven to be safe. Many induce new humoral and cellular immune responses against HIV. The final important question remains, whether any of these vaccines used as therapeutic immunogens generate immune responses that induce an altered disease course with a prolonged asymptomatic period without immunodeficiency, whether vaccines can affect increased viral clearance, or decreased transmission/infectivity? There remains no in vitro assay known to correlate with lack of disease progression, no immune profile consistent with a prolonged asymptomatic period. The vaccine therapy trial researchers seek the answers to these important questions. No single research organization can begin to address all the possibilities, so the overall pace of exploration of this therapeutic concept is likely to be dictated by the level of cooperation between the many groups involved in these studies. Open collaboration between researchers and open exchange of reagents, immunogens for in vitro experiments, and sera will allow faster dissection of the many questions and issues raised in this chapter. Whether vaccine therapy proves to have a useful role in the treatment of HIV-1 induced disease, these studies will ultimately lead to the development of useful techniques and provide new insights into the nature of the immunological responses, as the investigation of vaccine therapy did over a century ago. PMID- 8217901 TI - Risk of HIV infection in health care workers. PMID- 8217902 TI - Patient rights and physician responsibility: four problems in AIDS care. PMID- 8217903 TI - Bacillary angiomatosis. AB - The manifestations of bacillary angiomatosis include diverse cutaneous lesions, visceral parenchymal bacillary peliosis of the spleen and liver, and involvement of single or multiple organ systems. The organisms causing BA are R. henselae and R. quintana, and these organisms have now been cultured from the spleen and cutaneous lesions of BA as well as the blood of patients with visceral and cutaneous BA. The antibiotic regimen of choice for HIV-infected patients is erythromycin 500 mg 4 x a day for 2-4 months, but relapse may necessitate lifelong suppressive therapy. We are maintaining a registry of patients with bacillary angiomatosis and request that we be contacted (415-206-8680, UCSF) if you diagnose a case, preferably before therapy is instituted. PMID- 8217904 TI - Syphilis in HIV-infected persons. AB - Since syphilis and HIV infection are associated with each other at a higher rate than expected by chance, all HIV-infected persons and persons with syphilis should be tested for syphilis and vice versa. Because the immunological dysfunction of HIV-infected patients can interfere in clearing of T. pallidum, concomitant infection with T. pallidum requires that maximal doses of appropriate antibiotics be given (Table 2). Although falling nontreponemal titers, especially in early HIV stages, is evidence of adequate treatment, some appropriately treated HIV-infected persons will maintain a high persistent titer. If reinfection is ruled out, they require only one or two retreatments. Because some HIV-infected persons will inappropriately decrease their titer level, only adequate treatment (Table 2) gives the clinician confidence that the patient is cured. PMID- 8217905 TI - Tuberculosis and HIV disease. PMID- 8217906 TI - New developments in the management of Pneumocystis carinii disease. PMID- 8217907 TI - Three-dimensional reconstruction: methods of improving image registration and interpretation. AB - (i) Image registration. The use of serial images for computerised three dimensional reconstruction necessitates the inclusion of three separate sources of information at the stage of data input. These are (i) artificial registration points or fiducials, (ii) a calibration scale and (iii) an outline of each slab of the section to be included in the reconstruction. Most traditional methods rely on the production of drawings of the contours of the structure under investigation which also include both registration points and a calibration scale. We report on a method which considerably reduces the time involved at this labour intensive stage of reconstruction and in addition allows subsequent reconstructions of different structures to be performed without new drawings. Use is made of computerised alignment of tissue sections and the production of composite photomicrographs of both the tissue under investigation and an accurately registered stage micrometer scale. (ii) Improving image interpretation. Images derived from computerised three-dimensional reconstruction can be affected by the number of coordinates used to form the contour of each slice of a structure and by the number of slices that are used to construct the final model. Too little or too much data can considerably reduce the ability of the observer to interpret accurately the image generated by the computer. We report on a feature-based method which enables the experimenter to assess objectively the amount of data required in the two-dimensional plane, i.e. the number of data points per slice, and the three-dimensional plane, i.e. number of slices per structure, so that optimal reconstructions are generated. PMID- 8217908 TI - Comparative DNA image cytometry in imprint-, cytospin- and tissue section preparations of breast carcinoma. AB - Histologic sections, imprint preparations and cell preparations by enzymatic lysis from thick sections of cases of breast carcinomas were used to study total nuclear DNA distribution by image cytometry. Histologic sections are a prerequisite to unequivocally identify tumour cells as well as whole connective tissue cells used as a standard. While imprint preparations and lysis preparations are quite comparable with respect to distributional features, only one of them suffices to recognize these features, especially peaks at higher ploidies. Using this two-method approach to breast carcinomas, it was possible to distinguish a distribution separate from previously recognized distributions: a distinct triploid peak appears for predominantly high grade malignant ductal carcinomas. PMID- 8217909 TI - Towards an objective prognostic index of acute graft-versus-host disease. AB - Acute graft-versus-host disease (AGVHD) is one of the major complications of allogenic non-T-depleted HLA-compatible bone marrow transplantation. It is not yet possible to predict the clinical evolution of the disease at the time of its first manifestation. Twenty patients who initiated the disease with only moderate skin involvement were selected consecutively among those followed between January 1985 and December 1988 in the Bone Marrow Transplantation Unit, Saint Louis Hospital, Paris. A skin biopsy was performed at the onset of the AGVHD for each patient. For each biopsy, one 5-microns thick section was fixed by Bouin's solution, stained with hematoxylin and eosin and studied by image analysis at a final calibration of 7.6 pixels/microns. Ten patients did not exceed grade I (low risk group) and ten developed a more severe grade (high risk group) in the evolution of the disease. The mean and coefficients of variation, skewness and kurtosis of dimension-, form- and texture-related parameters of the nuclei of lymphocytes infiltrating the skin were investigated for their ability to discriminate between the high and low risk groups. The best discrimination was obtained using texture-related variables. An index containing 5 texture-related variables gave the maximum separation between the two groups, with a 100% correct classification. Our results represent a learning-step towards the development of a prognostic index of AGVHD. PMID- 8217910 TI - Detection of chromosome 1 aberrations by fluorescent in situ hybridization (FISH) in the human breast cancer cell line MCF-7. AB - In situ hybridization using nucleic acid probes specific for a particular chromosome repetitive sequence makes it possible to determine the number of corresponding chromosomes and potential aberrations in each cell of the population under investigation. The number of in situ hybridization spots per nucleus, indicating chromosomal ploidy and/or aberrations, thus marks the possible cell subpopulations having an abnormal karyotype. Applying such an interphase cytogenetics approach on the MCF-7 human breast cancer cell line with centromeric (pUC 1.77) and telomeric (1p-79) probes specific for repetitive sequences on the chromosome 1, we investigated the heterogeneity of the cell population on the basis of the number of fluorescent in situ hybridization (FISH) spots per nucleus and their location with respect to the others. We also followed the chromosome 1 genetic drift as the cell population aged. Our results confirmed the already known trisomy for the chromosome 1 in this cell line and demonstrated a deletion and a translocation of its telomeric sequence. Moreover, a subpopulation of cells with six chromosomes 1 representing a few percent of the population was transiently detected. PMID- 8217911 TI - Effects of isolation conditions on the cytometric evaluation of chromatin structure in rat myocardial nuclei. PMID- 8217912 TI - Professor Derek Russell Davis (1914-1993). PMID- 8217913 TI - Models of health and disease. AB - This paper describes and analyses six models of health and disease. These are: religious, biomedical, psychosomatic, humanistic, existential and transpersonal. Of these six models, only one was unequivocally reductionist: the biomedical. The others were all holistic. The religious, humanistic and transpersonal models could be considered as health models, the biomedical, psychosomatic and existential models as disease or illness models. The different models were assumed to depict different, but related, ways of representing health and disease. It is probable that different groups in society, including the different groups in the health service--doctors, nurses and patients--look at health and illness from partly different models. This is considered to have significant implications for the health service. PMID- 8217914 TI - On desire: its development and some clinical examples. AB - This paper defines a progression through five aspects of the concept of desire: (1) the Hegelian concept of desire given to Jacques Lacan by Alexandre Kojeve; (2) Lacan's subsequent addition of the Freudian concept; (3) Anthony Wilden's redefinition of the Lacanian rendition used to illustrate some aspects of clinical practice; (4) the Freudian theory of social behaviour recapped: a tension exists between what the mass of others expects us to do and what we want to do; and finally (5) the philosopher Stuart Hampshire's elucidation of how desire may be known. This paper combines these authors' expositions of desire and sketches out its meaning and relevance for practitioners. PMID- 8217915 TI - Mother-son incest as a defence against psychosis. AB - In the following, a case of mother-adult son incest is described and explained from a psychoanalytical viewpoint. Two theories are put forward: (a) Mother-son incest may occur as a defence against psychosis, and (b) the incest represents an unconscious search for triangulation, a process in which external authorities (such as, for example, a court of law) may function as surrogates for persons who have been missed in the pre-oedipal past. It is therefore possible to understand mother-son incest symbolically as an indicator of pre-oedipal needs of the son and of the mother's longing for the absent partner. The incest is, however, not only a cry for help; it is also to be regarded as an attempt to solve the problem for both people involved. Looked at in this way, new ways of understanding and new possibilities for therapy emerge. PMID- 8217916 TI - The integrative effect of reformulation: cognitive analytic therapy with a patient with borderline personality disorder. AB - The impact of 26 sessions of Cognitive Analytic Therapy on a patient with a borderline personality disorder is presented, largely through the patient's account given at a follow-up assessment interview. It is suggested that the account raises questions of practical and theoretical interest. PMID- 8217917 TI - Bereavement reactions of female Scots and Swazis: a preliminary comparison. AB - Forty matched Scottish and Swazi girls and women reported the intensity of the bereavement reactions which they had experienced two weeks and one year after the death of a close relative. The Swazi respondents reported more intense grief reactions during the first two weeks of bereavement than the Scottish participants, but the only way in which the two nationalities differed one year after the death was that the Scottish participants had a greater tendency to report feelings of guilt than the Swazi respondents. It is suggested that ritualistic crying and saying farewell to a dying relative may intensify feelings of grief during the early days of bereavement but, in the context of a clearly defined period of mourning, may play a part in reducing later feelings of guilt. Nationality was not a good predictor of the overall bereavement reaction at either of the time periods. A better prediction was obtained from the number of exchanges with other people which were perceived as being unhelpful, and the number of interactions which were absent but longed for. PMID- 8217918 TI - Type A personality and marital intimacy in amputees. AB - The specific characteristics of the Type A personality have generated a great deal of recent attention due to the prevalence of these characteristics in persons suffering from coronary heart disease. Type A individuals are more likely to be involved in serious accidents and experience more secondary complications when faced with serious illness. They are also less apt to incorporate appropriate coping strategies to help deal with pain and discomfort, or to enlist the help of others for such purposes. These studies are particularly interesting for those involved in health care, as such personality characteristics may influence health and healing. The present study examines the Type A personality construct and marital intimacy in a sample of 34 lower extremity amputees. The Survey of Work Styles (SWS) was used to measure Type A behaviour patterns, and the Waring Intimacy Questionnaire (WIQ) to assess the marital relationship. When compared to a group of age- and sex-matched controls, lower extremity amputees showed higher prevalence of some Type A behaviour patterns, and, in males, lower levels of marital intimacy. The low return rate of questionnaires in this study limits its generalizability, but results remain consistent with predictions for Type A behaviour patterns. PMID- 8217919 TI - Is alexithymia a non-neurotic personality dimension? A response to Rubino, Grasso, Sonnino & Pezzarossa. AB - Rubino, Grasso, Sonnino & Pezzarossa (1991) reported a significantly higher level of alexithymia in neurotic and delusional patients than in psychosomatic patients, and concluded that alexithymia is not a non-neurotic personality dimension. Further empirical data are cited, however, that contradict this conclusion and support the view that alexithymia is a type of affect deficit. PMID- 8217920 TI - Reliability and validity of the Perinatal Grief Scale for women who experienced late pregnancy loss. AB - The psychometric qualities of the Perinatal Grief Scale (PGS) were evaluated in a sample of 46 Dutch women in late pregnancy (> or = 24 weeks), who had been informed of the diagnosis 'lethal or severe fetal malformation'. The validity was assessed by comparing it to the Impact of Event Scale and to a clinical diagnosis of psychological instability. The PGS appeared to be internally consistent and particularly strongly related to psychological instability. It can therefore be considered as a valid assessment instrument, also for women who experience late pregnancy loss. PMID- 8217921 TI - Biliary surgery via minilaparotomy--a limited procedure for biliary lithiasis. AB - Cholelithiasis until now has been treated using solvents, lithotripsy via a biliary endoscope, laser or shock wave lithotripsy, and laparoscopic cholecystectomy. I have developed a new surgical treatment for cholelithiasis in which a cholecystectomy is performed through a minilaparotomy. This paper presents this new technique and discusses the principles of surgery for cholelithiasis using this technique. This procedure is performed by a 2 to 3 cm subcostal skin incision in the right hypochondrium. More than 400 patients were treated by this technique. This procedure is not different in terms of blood loss or operation time from conventional methods, and no significant complications have occurred. Intraoperative X-ray examination is performed routinely because of easy insertion of a tube from the cystic duct into the bile duct. Reduction of the length of the incision greatly facilitates postoperative recovery, shortening the hospital length-of-stay to within 3 days. The surgical manipulation of only a limited area of the upper abdomen is unlikely to induce postoperative syndromes, such as adhesions or ileus. Following this experience, a biliary drainage procedure based on cholangionmanomery and primary closure of the choledochotomy was introduced. This approach allowed even patients with choledocholithiasis to undergo a minilaparotomy and be discharged within one week. PMID- 8217922 TI - Acute fulminant pancreatitis: debridement or formal resection of the pancreas. AB - During the ten year period from 1980 to 1989, 51 patients were treated at Oulu University Central Hospital for fulminant acute pancreatitis. Five were in a moribund state on admission and died shortly afterwards, 6 were treated conservatively and survived, and 40 were operated on, 17 by primary pancreatic resection and 23 by debridement of the peripancreatic area. Mortality rates were 53 per cent for the resection group and for the debridement group 22 per cent. Reoperations were performed in 24 per cent of patients in the pancreatic resection group and in 60 per cent of those in the debridement group. The high mortality rate associated with primary pancreatic resection has caused us to adopt a more conservative strategy, and surgical treatment is directed towards later complications of this severe disease. PMID- 8217923 TI - Clinical diversity in biliary pancreatitis--classification of two types. AB - One hundred and seven patients with biliary pancreatitis undergoing operation from 1976 to 1989 were reviewed. To clarify the reason for failure to respond to conventional supportive therapy, 73 patients (68%) who underwent emergency surgery were retrospectively divided into two groups according to the severity of the pancreatitis evaluated at laparotomy and compared. Sixty-two had minimal or mild pancreatitis (Group I), among whom 44 (71%) had life-threatening acute biliary tract disease. All underwent biliary surgery and 4 (6%) subsequently died, 2 due to acute obstructive suppurative cholangitis. Eleven had hemorrhagic necrotizing pancreatitis (Group II), among whom 7 had complications of acute pancreatitis such as pancreatic ascites or abscess. These underwent pancreatic and/or biliary surgery and 3 (27%) died of multi-organ failure. There appears to be two types of biliary pancreatitis refractory to conventional supportive therapy, which differ in the extent of surgery required and in mortality: (1) minimal or mild pancreatitis with persistent life-threatening acute biliary tract disease (biliary type), and (2) more severe pancreatitis (pancreas type) early in the course of the disease. PMID- 8217924 TI - Hepatic branch vagotomy can suppress liver regeneration in partially hepatectomized rats. AB - The role of the vagus nerve in liver regeneration after partial hepatectomy was studied by comparing the effects of hepatic branch vagotomy with those of hepatic branch sympathectomy in rats. The liver weight as a percentage of body weight decreased significantly 7 days after vagotomy compared with the controls and this was associated with a reduction in food intake. There was no difference in the liver weights between the control rats and the pair-fed vagotomized rats. Hepatic sympathectomy had no significant effect on the liver weight. The serum scores indicating hepatic function showed no difference between the control and the vagotomized rats except alkaline phosphatase. The concentration of insulin was unchanged. The number of mitotic hepatocytes remained high at 7 days after vagotomy. These observations led us to conclude that the vagus nerve stimulates liver regeneration, and its effect depends on vagal factors directly and specifically. PMID- 8217925 TI - The outcome of cholangitis after percutaneous biliary drainage in neoplastic jaundice. AB - The purpose of this paper is to evaluate factors affecting the outcome of cholangitis after PTBD in jaundiced cancer patients. Twenty nine patients with neoplastic jaundice (male/female ratio 13/16, median age 55 years) with full clinical data, were treated by PTBD and developed cholangitis at a median of 9 days later. Four patients (14%) died of biliary sepsis a median of one month after PTBD while the other 25 survived a median of 6 months, with one week median duration of cholangitis. The probability of the cholangitis resolving was analyzed by time to resolution and it was found that 50% and 100% of the recoveries occurred 5 and 9 months respectively from the onset of the complication. The series was analyzed to determine the role of several variables (disease/patient/treatment related) in the resolution of cholangitis. Only a low stricture site, a large initial drainage catheter (10F) and a temperature increase exceeding 39 degrees C were correlated with a positive outcome. We conclude that PTBD-related cholangitis has, in our experience, a good chance of cure, low mortality rate and satisfactory 6 months median survival. PMID- 8217926 TI - Microcystic adenoma of the pancreas: observation or treatment? PMID- 8217927 TI - Biliary duct granular cell tumor: a rare but surgically curable benign tumor. AB - Granular [correction of Granulosa] cell tumors are rare benign tumors which may be found throughout the body. Rare cases are isolated within the biliary tree. If completely resected, surgical excision is curative. A case of biliary duct granular [correction of granulosa] cell tumor is presented with review of the world's literature on this topic. PMID- 8217928 TI - Common bile duct obstruction by free floating tumor. AB - Tumors usually spread by local invasion or by vascular or lymphatic metastases. We report six patients in whom tumor cells were shed into the common bile duct with resulting obstruction. The three men and three women had jaundice and upper abdominal discomfort. Jaundice was intermittent in four patients. Preoperative total serum bilirubin ranged from 2.5 to 16.1 mg/dl; alkaline phosphatase ranged from 221 to 605 IU/1. Ultrasound showed a dilated gallbladder [GB] in five patients with dilated intrahepatic ducts in three and stones in only one. ERCP showed a single filling defect in two of three patients and multiple defects in one. PTC showed multiple defects in one patient. At operation a thick gelatinous tissue fragment or clot was seen in the common bile duct of each patient. Frozen section identified tumor tissue in all. The source was GB carcinoma [2], GB adenomyoma [1], hepatic metastases of colon cancer [2] and common bile duct cancer [1]. Treatment consisted of pancreaticoduodenectomy [2], including one for GB cancer, left hepatic lobectomy [1], choledochoduodenostomy [1], common duct exploration with T-tube insertion [1] and cholecystectomy [1]. One patient with metastatic colon cancer and another with gallbladder cancer died within one year of operation. The other four are alive from 2 to 4 years later. CONCLUSION: Benign or malignant tumors within the hepatobiliary tree can shed tissue into the common bile duct which can cause biliary obstruction. Any tissue fragment found in the common bile duct should be evaluated by frozen section. Recognition of this mode of tumor spread is needed for appropriate therapy of the underlying benign or malignant tumor. PMID- 8217929 TI - Antibiotics with percutaneous aspiration or drainage for pyogenic liver abscess. PMID- 8217930 TI - Prophylactic sclerotherapy for oesophageal varices. PMID- 8217931 TI - Budd-Chiari syndrome--transplant, meso-atrial shunt or combined portocaval shunt with cavo-atrial shunt. PMID- 8217932 TI - Organization of texture segregation processing in primate visual cortex. AB - We investigated the intracortical organization of neuronal mass activity that is related to texture segregation on the basis of orientation contrast. Evoked potentials were recorded to a stimulus, signalling a contribution from texture segregation-sensitive mechanisms by means of specific response components. The specific components could only be recorded when textons had a spatial organization that leads to the percept of image segmentation. Equivalent dipole estimations of the specific response components suggested the presence of texture segregation-related activity in the primary visual cortex. These results were corroborated by current-source-density analysis of intracortical recordings in the awake monkey. A specific involvement of layers 2/3 and 5 of area 17 in the global process of image segmentation could be demonstrated. PMID- 8217933 TI - Sensitization and multiplicative noise in the descending contralateral movement detector (DCMD) of the locust. AB - Spike discharges from the descending contralateral movement detector (DCMD) were recorded extracellularly from the ventral nerve cord of the locust in complete darkness, in response to dim flashes of constant-intensity light, and in response to pairs of identical flashes presented different intervals apart. Three phenomena were discovered: novel long-term sensitization which changes the DCMD's sensitivity to light, a multiplicative cascade process driven by shot events, and the suppression of the spike discharge shortly after a dim flash. The DCMD's spike discharge is stochastic. It can be considered as a two-stage cascade process producing intrinsic multiplicative noise. An effective photon, or thermal isomerization in complete darkness, produces an unseen shot event which in turn initiates a random number of DCMD spikes in a cluster. A short initiates a variable number of spikes when it directs the rate of a Poisson process. The results of statistical analyses are consistent with this model when the amplitudes of shot events are variable. The transmission efficiency is low because at least 2.4-9.6 quantum bumps are required to produce one extra DCMD spike. The DCMD has a constant mean discharge rate of 0.25-1.5 spikes/s in complete darkness. Clustering about particular points in time (shots) leads to a lack of independence between interspike intervals, and the overdispersion of interspike interval and number distributions compared with those from a simple Poisson process. The mean cluster size is 1.3-1.6 spikes in darkness. Similar clustering was found in response to flashes of light. A dim flash changes the DCMD's sensitivity to light, even at threshold when no spike discharge results. Sensitization occurs because the average number of shot events produced by isoquantal flashes depends on the history of visual stimulation. This contributes to the nonlinear response-intensity function. The evolution of sensitization is roughly constant in different DCMD cells, lasting approximately 3 s after a flash. Sensitization was observed in response to light only, presumably because the intensity of dark-light is too low. It is proposed that sensitization is associated with a set of processes or molecular state in the presynaptic region of a chemical synapse. PMID- 8217934 TI - Dynamics of orientation coding in area V1 of the awake primate. AB - To investigate the importance of feedback loops in visual information processing, we have analyzed the dynamic aspects of neuronal responses to oriented gratings in cortical area V1 of the awake primate. If recurrent feedback is important in generating orientation selectivity, the initial part of the neuronal response should be relatively poorly selective, and full orientation selectivity should only appear after a delay. Thus, by examining the dynamics of the neuronal responses it should be possible to assess the importance of feedback processes in the development of orientation selectivity. The results were base on a sample of 259 cells recorded in two monkeys, of which 89% were visually responsive. Of these, approximately two-thirds were orientation selective. Response latency varied considerably between neurons, ranging from a minimum of 41 ms to over 150 ms, although most had latencies of 50-70 ms. Orientation tuning (defined as the bandwidth at half-height) ranged from 16 deg to over 90 deg, with a mean value of around 55 deg. By examining the selectivity of these different neurons by 10-ms time slices, starting at the onset of the neuronal response, we found that the orientation selectivity of virtually every neuron was fully developed at the very start of the neuronal response. Indeed, many neurons showed a marked tendency to respond at somewhat longer latencies to stimuli that were nonoptimally oriented, with the result that orientation selectivity was highest at the very start of the neuronal response. Furthermore, there was no evidence that the neurons with the shortest onset latencies were less selective. Such evidence is inconsistent with the hypothesis that recurrent intracortical feedback plays an important role in the generation of orientation selectivity. Instead, we suggest that orientation selectivity is primarily generated using feedforward mechanisms, including feedforward inhibition. Such a strategy has the advantage of allowing orientation to be computed rapidly, and avoids the initially poorly selective neuronal responses that characterize processing involving recurrent loops. PMID- 8217935 TI - Cortical afferents of visual area MT in the Cebus monkey: possible homologies between New and Old World monkeys. AB - Cortical projections to the middle temporal (MT) visual area were studied by injecting the retrogradely transported fluorescent tracer Fast Blue into MT in adult New World monkeys (Cebus apella). Injection sites were selected based on electrophysiological recordings, and covered eccentricities from 2-70 deg, in both the upper and lower visual fields. The position and laminar distribution of labeled cell bodies were correlated with myeloarchitectonic boundaries and displayed in flat reconstructions of the neocortex. Topographically organized projections were found to arise mainly from the primary, second, third, and fourth visual areas (V1, V2, V3, and V4). Coarsely topographic patterns were observed in transitional V4 (V4t), in the parieto-occipital and parieto-occipital medial areas (PO and POm), and in the temporal ventral posterior area (TVP). In addition, widespread or nontopographic label was found in visual areas of the superior temporal sulcus (medial superior temporal, MST, and fundus of superior temporal, FST), annectent gyrus (dorsointermediate area, DI; and dorsomedial area, DM), intraparietal sulcus (lateral intraparietal, LIP; posterior intraparietal, PIP; and ventral intraparietal, VIP), and in the frontal eye field (FEF). Label in PO, POm, and PIP was found only after injections in the representation of the peripheral visual field (> 10 deg), and label in V4 and FST was more extensive after injections in the central representation. The projections from V1 and V2 originated predominantly from neurons in supragranular layers, whereas those from V3, V4t, DM, DI, POm, and FEF consisted of intermixed patches with either supragranular or infragranular predominance. All of the other projections were predominantly infragranular. Invasion of area MST by the injection site led to the labeling of further pathways, including substantial projections from the dorsal prelunate area (DP) and from an ensemble of areas located along the medial wall of the hemisphere. In addition, weaker projections were observed from the parieto-occipital dorsal area (POd), area 7a, area prostriata, the posterior bank of the arcuate sulcus, and areas in the anterior part of the lateral sulcus. Despite the different nomenclatures and areal boundaries recognized by different models of simian cortical organization, the pattern of projections to area MT is remarkably similar among primates. Our results provide evidence for the existence of many homologous areas in the extrastriate visual cortex of New and Old World monkeys. PMID- 8217936 TI - Human cone receptor activity: the leading edge of the a-wave and models of receptor activity. AB - The leading edge of the a-wave of the electroretinogram (ERG) was evaluated as a measure of human cone photoreceptor activity. The amplitude of the cone a-wave elicited by flashes of different energy was compared to the predictions of a class of models from in vitro studies of cone photoreceptors. These models successfully describe the leading edge of the a-wave. Thus, the human cone a-wave can be used to test hypotheses about normal and abnormal cone receptors. The ability of the human cone to adjust its sensitivity in the presence of steady adapting lights was assessed by recording cone a-waves to flashes on adapting fields up to 3.9 log td in intensity and by comparing these responses to quantitative models of adaptation. The first 10 ms of the cone's response is little affected by field intensities up to 2.9 log td. The 3.9 log td field reduced the response to weak flashes by about a factor of 2.5 (0.4 log unit). This relatively small reduction in sensitivity can be attributed to a combination of response compression, pigment bleaching, and an adaptation mechanism that changes the gain without changing the time course. We conclude that either the human cones show relatively little adaptation or that they have an adaptation mechanism that involves a time-course change. That is, as we are limited with the a-wave to the first 10 ms or so of the cone's response, we cannot rule out a gain mechanism linked to a time-course change. PMID- 8217937 TI - Binocular interaction in the optokinetic system of the crab Carcinus maenas (L.): optokinetic gain modified by bilateral image flow. AB - We recorded optokinetic eye movements of the crab, Carcinus maenas, in split-drum experiments. The patterns were either oscillated in antiphase on both sides mimicking translational image flow or they were oscillated in phase producing rotational image flow. Eye movements elicited by the rotational stimulus were larger than those produced by the pseudotranslational pattern movements. The smaller response to the latter is mainly a consequence of binocular interaction, the strength of which depends on both the phase-shift and amplitude of pattern oscillation. We develop two hypotheses to explain our results: either (1) signals from each eye modify the gain of the linkage signals coming from the other eye, or (2) the signals coming from the other eye modify the gain of the control loop itself. Quantitative evaluation of the data favors the second of these two hypotheses, which comprises the models of Barnes and Horridge (1969) and Nalbach et al. (1985). In addition, we found that it is the signals from the two slow channels of the crab's movement-detecting system that are transferred from one eye to the other, while signals of the fastest channel act almost exclusively ipsilaterally. We discuss our results as an adaptation by which an animal with panoramic vision compensates exclusively the rotational component of image flow during locomotion. The fact that freely walking crabs distinguish the two components of image flow better than restrained crabs indicates that further visual and nonvisual signals help to disentangle image flow. PMID- 8217938 TI - The retinal ganglion cell distribution and the representation of the visual field in area 17 of the owl monkey, Aotus trivirgatus. AB - The distribution of ganglion cells and displaced amacrine cells was determined in whole-mounted Aotus retinae. In contrast to diurnal simians, Aotus has only a rudimentary fovea. Ganglion cell density decreases towards the periphery at approximately the same rate along all meridians, but is 1.2-1.8 times higher in the nasal periphery when compared to temporal region at the same eccentricities. The total number of ganglion cells varied from 421,500 to 508,700. Ganglion cell density peaked at 15,000/mm2 at 0.25 mm dorsal to the fovea. The displaced amacrine cells have a shallow density gradient, their peak density in the central region is about 1500-2000/mm2 and their total number varied from 315,900 to 482,800. Comparison between ganglion cell density and areal cortical magnification factor for the primary visual cortex, area 17, shows that there is not a simple proportional representation of the ganglion cell distribution. There is an overrepresentation of the central 10 deg of the visual field in the visual cortex. The present results for Aotus and the results of a similar analysis of data from other primates indicate that the overrepresentation of the central visual field is a general feature of the visual system of primates. PMID- 8217939 TI - Synaptic connections involving immunoreactive glycine receptors in the turtle retina. AB - The distribution of glycine receptors in the turtle retina was studied with the aid of a monoclonal antibody that detects the 93-kD protein associated with the strychnine-sensitive glycine receptor. Light microscopically, receptors were found in the inner plexiform layer and, more sparsely, in the innermost parts of the inner nuclear layer. No receptors were seen to be associated with photoreceptor cells, horizontal cells, or any other structures in the distal inner nuclear layer or outer plexiform layer. Ultrastructurally, glycine receptors were found on the inner face of postsynaptic membranes of processes from amacrine and presumed ganglion cells and always involved amacrine cell processes as the presynaptic element. Such glycine receptor immunoreactive synapses onto amacrine cell processes were distributed throughout the inner plexiform layer with a peak density near the middle. On the other hand, output synapses onto ganglion cell processes displaying immunoreactive glycine receptor sites showed a bimodal distribution in the inner plexiform layer. Glycine receptor immunoreactivity was not detected on bipolar cells, but presumed glycine utilizing processes (i.e. those presynaptic to immunoreactive glycine receptors) were occasionally found to be postsynaptic in bipolar cell dyads. The majority of the synaptic input to the presumed glycine-utilizing amacrine cell processes was from other amacrine processes, some of which were themselves glycine utilizing. The observations suggest that glycinergic synapses in the turtle retina are, to a large extent, engaged in processing interamacrine signals. PMID- 8217940 TI - The retinoids of seven species of mantis shrimp. AB - Eyes of stomatopod crustaceans, or mantis shrimps, contain the greatest diversity of visual pigments yet described in any species, with as many as ten or more spectral classes present in a single retina. In this study, the eyes of seven species of mantis shrimp from three superfamilies of stomatopods were examined for their content of retinoids. Only retinal and retinol were found; neither hydroxyretinoids nor dehydroretinoids were detected. The principal isomers were 11-cis and all-trans. The eyes of most of these species contain stores of 11-cis retinol, principally as retinyl esters, and in amounts in excess of retinal. Squilla empusa is particularly noteworthy, with over 5000 pmoles of retinol per eye. PMID- 8217941 TI - Concentrations of phosphatidylinositol 4,5-bisphosphate and inositol 1,4,5 trisphosphate within the distal segment of squid photoreceptors. AB - Although inositol trisphosphate (InsP3) is a key substance in phototransduction of invertebrate photoreceptors, its intracellular concentration remains unknown. The purpose of this study was to assay its concentration and the concentration of its precursor, phosphatidylinositol bisphosphate (PtdInsP2), within squid photoreceptors. Rhabdomeric membranes were purified and their PtdInsP2 content measured with a phosphate assay after the extracted phospholipids were deacylated and separated by ion-exchange chromatography. At least 75% of the total PtdInsP2 found in the retinal homogenate was associated with the plasma membranes of the rhabdomeric microvilli, where PtdInsP2 was 3.1 +/- 0.7% of the total phospholipids, a level comparable to values published for rat brain. In terms of rhodopsin, microvillar membranes contained 3.7 +/- 0.9 mol PtdInsP2/mol rho. The InsP3 content of living retinas was measured with a radioreceptor assay. The basal content of dark-adapted retinas was 0.15 +/- 0.05 InsP3/rho, equivalent to 30 +/- 9 nmol/g tissue that is about twice that of rat brains. Flash illumination (approximately 1 ms in duration) that photoactivated 1% of rhodopsin increased the level about fivefold to 0.68 +/- 0.22 InsP3/rho. Corresponding decrease in PtdInsP2 was undetectable as it was within measurement errors. For PtdInsP2, the measured content corresponds to 5.6 +/- 1.4 mM within the volume of rhabdomere. Maximal light-induced concentration of InsP3 is calculated to be 1.2 +/- 0.4 mM within the cytoplasm of the distal segment. Each photoactivated rhodopsin leads to the formation of < or = 500 InsP3 molecules when measured 15 s after the flash.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217942 TI - Visual thresholds in mice: comparison of retinal light damage and hypopigmentation. AB - In previous electrophysiological experiments from hypopigmented animals (mice, rats, rabbits), single-unit recordings from both retinal ganglion axons and cells in the superior colliculus have demonstrated an increase in threshold in the dark adapted state which is roughly proportional to the animal's ocular melanin concentration. We have examined the thresholds in hypopigmented mice by using a behavioral water maze screening test and found similar threshold elevations to the electrophysiology. In the present study, we investigated the contribution of retinal light damage to the threshold elevation in an albino mouse strain which is relatively resistant to light damage (C57BL/6J c2J/c2J) and mice with profound retinal degeneration (C57BL/6J rd/rd). Black or albino littermates (C57BL/6J +/c2J or c2J/c2J) were placed in either constant light (350 cd/m2) or dim cycling light (0.001 cd/m2) for 21 days before testing. The normally pigmented animals had thresholds of 1.00 x 10(-5) cd/m2 regardless of their light history. The albino mice (c2J/c2J) maintained in constant light had a slight 0.30 log unit elevation compared to their controls that were maintained in dim cycling light 6.3 x 10(-4) cd/m2 (similar to previously published reports). We examined the retinal morphology of representative animals in semi-thin plastic sections. We could not detect any light damage (overall morphology or cell counts in the outer nuclear layer) in either the normally pigmented animals or the albino mice (c2J/c2J) maintained in dim cycling light. We found extensive light damage in the albino mice (c2J/c2J) maintained in constant light (virtual absence of photoreceptor outersegments) that corresponded to the slight elevation in threshold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217943 TI - Visual evoked potentials in dyslexics and normals: failure to find a difference in transient or steady-state responses. AB - We measured transient and steady-state checkerboard contrast-reversal visual evoked potentials (VEPs) in ten dyslexics, five patient controls, and 11 normals over a range of contrasts and luminances. Latency, amplitude, and phase measurements failed to distinguish the responses of dyslexics from those of normals or patient controls. Decreases in luminance or contrast resulted in an increased latency of the transient VEP in all groups, but these changes also did not distinguish the responses of dyslexics from those of the controls. Response variability was similar in dyslexics and normals, but was increased in subjects with attention deficit-hyperactivity disorder (ADHD). Performance on standardized psychometric testing did differentiate the dyslexics from controls, but did not correlate with VEP responses. PMID- 8217944 TI - Visual and vestibular reflexes that stabilize gaze in the chameleon. AB - Spontaneous eye movements as well as visual, vestibular, and proprioceptive cervical reflexes which contribute to gaze stabilization were investigated in the chameleon using the magnetic search-coil technique. The oculomotor range of each eye was very large (180 deg horizontally x 80 deg vertically). Spontaneous ocular saccades were independent in the two eyes and could have very large amplitudes. The fast phases of nystagmus during the stabilization reflexes were also independent in the eyes. In the head-restrained condition, optokinetic nystagmus (OKN) had a low gain in both horizontal and vertical planes (0.35 at 5 deg/s) and showed little binocular interaction. The vestibulo-ocular reflex (VOR) exhibited a low gain (0.2-0.3 from 0.05-1 Hz) and a high-phase lead at low frequency (140 deg at 0.05 Hz). Rotation of the animal in the presence of a visible surround increased the overall gain of gaze stabilization to 0.4-0.5 (P < 0.01) and considerably reduced the phase lead (38 deg at 0.05 Hz). In the head-free condition, head and eye reflexes were active simultaneously during both optokinetic and vestibular stimulation, but nystagmic head movements appeared only occasionally with a rather loose eye-head coordination. During optokinetic stimulation, eye movements contributed more than head movements to gaze stabilization, whereas, during vestibular or visuo-vestibular stimulation, the relative contribution of eye and head responses varied with stimulus frequency. When the head was freed, overall gain for gaze stabilization increased from 0.35 to 0.45 (P < 0.05) for optokinetic stimulation at 5 deg/s and from 0.2-0.3 to 0.4 0.75 (P < 0.001) for vestibular stimulation at 0.05-1 Hz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8217945 TI - The re-establishment of the representation of the dorso-ventral retinal axis in the chiasmatic region of the ferret. AB - This study has examined the representation of the dorso-ventral retinal axis in the optic nerve and tract of the ferret, as well as the associated fiber transformations which take place within the chiasmatic region. In one series of experiments, dorsal or ventral retinal lesions were made to induce fiber degeneration along the pathway, from which semi-thin sections were then stained for degenerating myelin. In a second series, implants of the carbocyanine dye, DiI, were made into the caudo-medial or rostro-lateral optic tract in order to label retrogradely the axons as they course through the chiasmatic region. Additional observations were made from the optic pathways of ferrets that had been similarly lesioned or implanted, but employing either a reduced-silver technique to reveal the degenerating axons or horseradish peroxidase as the retrograde label. The axons arising from the dorsal and ventral retina course in the dorsal and ventral parts of the optic nerve posterior to the eye, but as they continue along the nerve they disperse producing a highly impoverished retinotopy in the prechiasmatic portion of the nerve. As they course through the chiasmatic region, however, they become segregated again: dorsal fibers cross the midline relatively caudally while ventral fibers cross further rostrally, although there is overlap between them. Nearer the threshold of the optic tract, the fibers from dorsal and ventral retina undergo a further and more striking segregation, placing the dorsal fibers caudo-medially and the ventral fibers rostro-laterally within the tract. This re-emergence of retinotopic order implicates a fiber substrate interaction as being responsible for the axonal reordering, and suggests that fiber pre-ordering in the tract contributes to the formation of the orderly projection of the dorso-ventral retinal axis upon central visual targets. PMID- 8217946 TI - Effect of choroidal and ciliary nerve transection on choroidal blood flow, retinal health, and ocular enlargement. AB - Our previous studies suggested that reduced choroidal blood flow (CBF) occurs with manipulations that yield myopic eye growth and that these reductions are primarily a consequence of the ocular enlargement. We could not entirely rule out the possibility, however, that reductions in CBF are at least to some extent antecedent and causal to the ocular enlargement. We therefore in the present study examined the effects on eye size of artificially reducing CBF by unilaterally transecting the choroidal nerves of the ciliary ganglion in four-day old chicks. For comparison, we also transected the ciliary nerves in a second group of chicks or transected both ciliary and choroidal nerves in a third group of chicks. The effects of the nerve transections were evaluated in comparison to the effects of the orbital surgery itself (without nerve transection) in a fourth group termed the sham-operated control group. Two weeks after transection, CBF was measured using laser Doppler velocimetry, the ocular axial, nasotemporal and dorsoventral lengths were measured, and the eyes weighed. The results showed that CBF in birds with either choroidal nerve cuts or choroidal plus ciliary nerve cuts was greatly reduced in the treated eye (20-40% of nontreated eye). The treated eyes of these birds also showed gross depigmentation and histologically evident loss of the outer retina, most typically in the temporal retina. Birds with ciliary nerve cuts showed increased CBF in both eyes (131% right eye and 154% left eye compared to shams). Since ciliary nerve cuts yield fixed dilated pupils, increased CBF with ciliary nerve cuts appears consistent with the previously reported involvement of the choroidal nerves within a neural circuit subserving light-mediated upregulation of CBF. Clear effects on eye size were observed in the treated eyes in each group. The sham surgery alone yielded slight enlargement of the right eye compared to left eye, particularly in the axial dimension. In the choroidal nerve and the both nerve cut groups, nasotemporal and dorsoventral elongation were slightly diminished in the treated eyes compared to the sham-treated eyes. In contrast, enlargement of the right eye was slightly enhanced in the ciliary nerve cut group compared to the sham-treated eyes. The overall results suggest that large decreases in CBF do not enhance myopic eye growth, although large increases in CBF may. PMID- 8217947 TI - [Loco-regional immunotherapy with OK-432 and cultured autologous lymphocytes for patients with metastatic cancer]. AB - Metastases from breast or gastrointestinal cancers have been treated loco regionally with immunotherapy using OK-432 and cultured autologous lymphocytes since 1983. Response rate for patients with liver, lung, or pleural metastases from breast cancer was 57%, 53%, 90%, respectively, and for those with liver metastases from gastric or colo-rectal cancer was 31% or 29%. Survival of the patients with liver, pleural metastases from breast cancer, or with peritoneal seeding from gastric cancer was prolonged when compared with historical controls. Immunotherapy was one of significant prognostic factor to prolong the survival in patients with pleural effusion from breast cancer, with Stage IV breast cancer, or with peritoneal seeding from gastric cancer. Moreover, concomitant regression of non-treated metastatic sites after the response of treated disease was often observed especially in breast cancer patients with both liver and bone metastases or with Stage IV disease. Thus, loco-regional immunotherapy can show a systemic beneficial effect. PMID- 8217948 TI - [Establishment of a cisplatin-resistant human ovarian cancer cell line]. AB - A human ovarian cancer cell line designated "MH" was established from ascites of a patient with ovarian serous cystadenocarcinoma treated with cisplatin. This cell line was grown for more than 2 years and over 100 passages in medium RPMI1640 containing 10% FCS. The cell doubling time, saturation density and plating efficiency was approximately 6.3 days, 5.5 x 10(4)/cm2, and 42%, respectively. Chromosomal analysis revealed aneuploidy with a modal number of 72 and 14-19 types of marker chromosomes. CA125 was detected in both the original tumor and the cultured cells. This cell line is cisplatin-resistant (IC50: 3.28 microM) and has high protein kinase C activity. PMID- 8217949 TI - Semiautomated 14C-thymidine incorporation assay for in vitro screening of anticancer drug. AB - We developed a rapid screening test for anticancer drugs by using 14C-thymidine (14C-TdR), a microculture filtration plate and a radiochromatoscanner. Mitomycin C (MMC), tamoxifen and 5-fluorouracil (5FU) were used as the anticancer drugs against four human gastric cancer cell lines. The rates of cell inactivation (14C TdR uptake) determined with the radiochromatoscanner were almost the same as those determined with the liquid scintillation counter. Comparing the rate of cell inactivation obtained by our method with that obtained by proliferative activity of cells derived from the cell count, both assays showed the approximately same results by tamoxifen and MMC but the rates of cell inactivation by 5FU in two cell lines obtained by the 14C-TdR uptake assay was considerably lower than those obtained by the cell count. These results show that the radio-labeled DNA precursor uptake assay is not suitable for metabolic inhibitors of DNA synthesis. Ninety six samples on a plate, however, were assayed semiautomatically and rapidly just as well as in the tetrazolium-based calorimetric (MTT) assay. Therefore, our 14C-TdR uptake assay system is useful for the cancer chemotherapeutic agents except the metabolic inhibitors of DNA precursors. PMID- 8217950 TI - [Relationship between the Ki-67 nuclear antigen content and cell-cycle perturbation on WiDr cells treated with 5-FU]. AB - The profile of Ki-67 nuclear antigen content according to the change in the cell cycle of WiDr cells affected by 5-fluorouracil (5-FU) was studied by flow cytometry. The cases who received 10 micrograms/ml for 1 hr and showed reproliferation in the growth curve presented significant accumulation at G2M phases. However, significant increase of Ki-67 antigen content was not observed in G2M phases. Meanwhile, the cases who continuously received 10 micrograms/ml for 72 hr and showed the suppression of cellular proliferation without reproliferation presented gradual accumulation into S phase and Ki-67 antigen content was found to be significantly increased. This increase occurred in G1 phase, and the cells with Ki-67 antigen content of the largest increase in G1 phase shifted to S phase. It indicates a possibility that Ki-67 nuclear antigen content is destined to be controlled specifically in G1 phase of the cell-cycle. 5-FU seems to damage this regulation system and, as a result, increase Ki-67 nuclear antigen. PMID- 8217951 TI - Immortalization of differentiated human hepatocytes by a combination of a viral vector and collagen gel culture. AB - Adult human and chimpanzee hepatocytes, which have no proliferative potential in vitro, were immortalized by introducing an oncogene encoding simian virus 40 large tumor(T) antigen by means of infection with a recombinant adenovirus vector. The frequency of immortalization was enhanced by a suspension method for virus adsorption and especially by using a collagen gel culture. The replicating hepatocyte colonies were isolated and selected by albumin secretion which is specific for parenchymal hepatocytes, then continuously subcultured. The immortalized hepatocyte lines also secreted other hepatocyte-specific proteins (complement C3, transferrin, fibrinogen). However, the amount of protein secretion declined with subculture. The subline RY5, cloned from a human immortalized line, showed relatively stable albumin secretion. Therefore, chromosomal studies and anchorage-independent growth properties were discussed and compared with its original line. PMID- 8217952 TI - [Effective removal of the contaminating host fibroblasts for establishment of human-tumor cultured lines]. AB - We report a useful method for the establishment of cell lines in vitro from human tumors. One of the obstacles to establishing pure human cancer cells in vitro is contaminating fibroblasts in cultures. This obstacle could be overcome by selective-growth control of fibroblasts treated with serum-free GIT medium and their selective elimination with antibiotic Geneticin (G418-sulfate). In this study, the process of establishing cultured cell lines from two oral cavity cancers is demonstrated using GIT medium and Geneticin. The comparative study of the growth of cells of the two oral cavity cancers and of two control normal fibroblast cell lines supported the selective growth inhibition and elimination of normal fibroblasts by the "G-G method". PMID- 8217953 TI - [Ligase chain reaction (LCR)]. AB - Ligase chain reaction (LCR) is a ligation-mediated amplification technique of a target DNA sequence using oligonucleotides and thermostable ligase. LCR is useful for the detection of known DNA sequences and point mutations in a limited amount of DNA. We introduce the principle, development, and protocol of this simple and convenient technique for DNA analysis. PMID- 8217954 TI - [Recent topics on Langerhans cells]. PMID- 8217955 TI - [Surgical treatment for metastatic lung tumors--with special references to colorectal lung metastases]. AB - Between 1960 and 1991, 103 consecutive patients underwent pulmonary resection for metastatic lung tumors in our department. Of the 103 cases 52 were males and 51 were females, aged from 21 to 83 years old. The items of the primary origin of them were 23 cases colorectal cancer, 21 of osteogenic sarcoma, 11 of soft part sarcoma, 10 of mammary cancer, 7 of choriocarcinoma, 7 of renal cancer and others. The 5 year survival of the colorectal lung metastases were examined according to the number and size of the tumors, the tumor free interval and operation modalities. The 5 year survival rate was 45%. The recent trends of surgical treatment for metastatic lung tumors show a significant decrease of surgical treatment of choriocarcinoma, however trends show a significant increase of colorectal carcinoma. The surgical treatment of the colorectal cancer metastases, not only solid metastasis and, multiple metastases but also localized liver metastasis have given satisfactory results. With the present state of chemo therapy and radiation therapy an acceptable survival rate cannot be expected except for only some kinds of metastatic tumor, and so most other tumors should be surgical resected. In particular it is desirable that a lobectomy with lymph node dissection be performed on solid colorectal metastasis. PMID- 8217956 TI - [E-cadherin expression and cancer invasion and metastasis]. AB - E-cadherin (ECD) is a transmembrane glycoprotein that mediates the calcium dependent adhesion of cells and plays a major role in cell-cell adhesion of normal epithelium. In present study, we have established the positive ECD expressed clone (ECD(+)) and the negative ECD expressed clone (ECD(-)). Anti human ECD monoclonal antibody (HECD-1) disturbed the mutual adhesion of ECD(+) effectively but didn't disturb that of ECD(-). ECD(+) did not invade the collagen/fibroblast gel, but ECD(-) did. Furthermore, ECD(+) acquired invasiveness in the collagen gel when HECD-1 was used. Clinicopathologically, we have investigated the correlation between expression of ECD and metastasis in human esophageal and gastric cancers by immunohistochemical staining using HECD 1. ECD expression of these lymph node metastatic tumor in the primary sites was more reduced than that of non metastatic tumor significantly. These results indicated that reduction or dysfunction of ECD diminishes intercellular adhesion and acquires invasive and metastatic capacity in human cancer cells. PMID- 8217957 TI - Identification of orbital lymphatics: enzyme histochemical light microscopic and electron microscopic studies. AB - The presence of orbital lymphatics in the primate model is demonstrated using light and electron microscopic enzyme histochemistry. In addition, strictly morphological definitions of lymphatics, such as discontinuous basal lamina, thin and irregular walls, anchoring filaments, and attenuated endothelial cell cytoplasm, were applied. This study confirmed the presence of conjunctival lymphatics reported by others. It also clearly demonstrated the presence of orbital arachnoid and lacrimal gland lymphatics that have not been previously described. A few areas of the extraocular muscles and connective tissue at the orbital apex also showed evidence of the presence of lymphatic vessels. Additional work is needed to define the nature and extent of orbital lymphatics as well as their connection to the extraorbital lymphatic system. PMID- 8217958 TI - Mucoepidermoid carcinoma of the lacrimal gland: 25 cases and a review and update of the literature. AB - Twenty-five cases of mucoepidermoid carcinoma of the lacrimal gland are compiled, the largest series reported to date. Five of these have not been previously reported. Additional follow-up is presented for seven cases previously reported in the literature, and 13 other cases from the literature are reviewed. This study suggests that histologic grading of the tumor into low- (grades 1 and 2) and high-grade (grade 3) tumors is most predictive of prognosis and can be used to formulate a therapeutic plan. Of the 16 patients with a known histologic grade for their tumors, 8 had low-grade tumors and 7 of these patients survived after extirpation with or without radiotherapy. On the other hand, only 1 of the 8 patients with high-grade tumors for which extended follow-up was available has remained tumor free. The authors suggest that low-grade tumors can be treated with complete extirpation with or without adjuvant radiation and that these tumors generally have a good prognosis. Grade 3 tumors, on the other hand, may be treated aggressively with exenteration and excision of bone, if needed, as well as adjuvant radiation. But these tumors, despite this treatment, carry a poor prognosis. PMID- 8217959 TI - Botulinum B toxin as an alternative to botulinum A toxin: a histologic study. AB - Histochemical effects of botulinum B toxin were studied on fibers from longissimus dorsi muscle in Albino rabbits and compared to effects produced by botulinum A toxin. Acetylcholinesterase staining, muscle fiber size analysis, and ATPase staining indicated botulinum B toxin produced a denervation gradient and field similar to that produced by botulinum A toxin. At 5 weeks postinjection with botulinum B toxin, analysis showed muscle fiber size variability, and diffuse acetylcholinesterase fiber staining comparable to botulinum A toxin at the injection site. Muscle sections taken at 4.0 cm for analysis showed statistically significant decreased fiber size variability and contraction of acetylcholinesterase staining pattern for both immunotypes. In addition, the denervation reflected by histochemical staining and fiber size analysis appeared transient and lasted for approximately 3 months for both immunotypes. These findings suggest botulinum B toxin produces pharmacologic effects on innervation of striated muscle similar to botulinum A toxin. Because immunologic tolerance has been demonstrated after therapeutic botulinum A toxin injections, further clinical studies need to be conducted with other immunotypes of toxin with no cross-reactivity to type A. PMID- 8217960 TI - Use of Vicryl (polyglactin-910) mesh implant for repair of orbital floor fracture causing diplopia: a study of 28 patients over 5 years. AB - Over the past 5 years, Vicryl mesh (polyglactin-910) implants were used successfully to reconstruct the orbital floor in 28 patients with significant preoperative diplopia due to orbital floor fractures. The layered mesh is available in 26.5 x 24 cm sheets, each of which is folded onto itself into 24 layers and packaged; 24 layers are approximately 4 mm thick. Appropriately sized implants varying in thickness from 6 to 56 layers were used to cover and fill the orbital floor defect. Absorbable Vicryl mesh is well-tolerated by orbital tissues; since it is soft and pliable, it is unlikely to compress orbital structures such as the optic nerve, lacrimal sac, or extraocular muscles. A second surgical site necessary for autogenous implants is avoided. The Vicryl mesh implant is technically easy to insert and does not require fixation in the orbit. Because Vicryl mesh is absorbable, the risks associated with permanent alloplastic implants are reduced. Similarly, there is no potential spread of communicable disease with homologous tissue implants. Follow-up ranged from 1 month to 2 years (median, 13 months). None of the patients had late complications. The only complication was transient, low-grade eyelid inflammation in four patients. PMID- 8217961 TI - Unilateral congenital ptosis: compensatory head posturing and amblyopia. AB - Patients with unilateral congenital ptosis often adopt chin elevation to maintain fusion. This compensatory head posturing has been considered a sign of fusion, thus indicating a low risk for amblyopia. To evaluate this sign, we reviewed the charts of 11 preverbal children with unilateral congenital ptosis who had straight eyes and appropriate compensatory head posturing to maintain binocular vision. Four additional patients with unilateral ptosis and no compensatory head posturing were tested for comparison. All patients had undergone an examination and had been tested by pattern Visual Evoked Potential (VEP) under chloral hydrate sedation. Five of the 11 patients with compensatory head posturing were found to be amblyopic, three moderately so and two severely affected. The four patients without compensatory head posturing were amblyopic. It is our hypothesis that compensatory head posturing allows peripheral fusion even when significant amblyopia is present. Additionally, the clinical sign of a compensatory head turn to maintain binocular vision does not rule out the presence of significant amblyopia. PMID- 8217962 TI - Stenotic puncta: microsurgical punctoplasty. AB - The successful long-term management of epiphora caused by punctal stenosis presents a difficult problem for the ophthalmologist. The purpose of this paper is to describe a successful procedure that respects lacrimal excretory anatomy and provides excellent results in the management of epiphora. Twenty-three patients (32 eyes) with punctal stenosis underwent excision of the stenotic puncta followed by microscopic externalization of the vertical canaliculus. At 6 months and 1 year, only one patient complained of tearing; at 2 years, three eyes experienced tearing and were successfully dilated; no eyes experienced tearing at 4 years. Only one patient experienced a dry eye, which was managed with topical lubricants. Microscopic punctoplasty thus provides excellent long-term management of epiphora from punctal stenosis with minimal disruption of anatomy. PMID- 8217963 TI - The use of the epiglottis as an autologous composite graft in eyelid reconstruction. AB - The use of the epiglottis as a composite graft in eyelid reconstruction is presented. Anatomy, histology, and physiology of the epiglottis are discussed. Two cases in which the epiglottis was used in reconstruction of lower eyelid deformities are reported. PMID- 8217964 TI - Intraoperative discovery of a neurofibroma during routine ptosis surgery. AB - A noncosmetic blepharoplasty with levator tuck was planned to repair a congenital ptosis presumed to be caused by levator maldevelopment. During surgery a mass was found in the lid, revealing the ptosis to be mechanical in nature. Biopsy and subsequent pathological exam revealed this to be a plexiform neurofibroma in a reportedly undiagnosed patient. PMID- 8217966 TI - Eyelid reanimation. PMID- 8217965 TI - Modified gold weights for reanimation of the upper lid in facial nerve paralysis. AB - A modified gold weight has been developed for use in paretic upper eyelids following seventh nerve damage. The modified weight is implanted in the pretarsal space. The weight was developed to enhance lid blinking, minimize extrusion, provide better cosmesis, and to provide a good upper lid blinking mechanism. PMID- 8217967 TI - Ambulatory blood pressure in pregnancy: measurements and machines. PMID- 8217968 TI - Sweeping of the membranes in prolonged pregnancy. PMID- 8217969 TI - Tamoxifen and the gynaecologist. PMID- 8217970 TI - Sweeping the membranes: a valid procedure in stimulating the onset of labour? AB - OBJECTIVE: To determine whether sweeping the membranes in pregnancies of longer than 40 weeks gestation results in an accelerated onset of labour and a reduction in the incidence of induction of labour. DESIGN: A prospective randomised controlled study. SETTING: The antenatal clinic of a district general hospital. SUBJECTS: One hundred and ninety-five antenatal women with pregnancies proceeding beyond 40 weeks gestation. INTERVENTIONS: A Bishop score assessment of the cervix alone or combined with a membrane sweep, on a randomised basis. OUTCOME MEASURES: Subsequent duration of pregnancy to the onset of spontaneous labour. The incidence of induction of labour for post-maturity. RESULTS: Sweeping the membranes significantly reduces the subsequent duration of pregnancy, from an average of five days to two days following the procedure. The proportion of inductions of labour was 8.1% in the swept group and 18.8% in the control group. No harmful side effects to the procedure were noted. CONCLUSIONS: Sweeping the membranes is a safe and useful procedure which results in a reduced incidence of post-mature pregnancies, and a subsequent reduction in the labour induction rate. PMID- 8217971 TI - Validation of the SpaceLabs 90207 ambulatory blood pressure monitor for use in pregnancy. AB - OBJECTIVE: To determine the accuracy of the SpaceLabs 90207 ambulatory blood pressure monitor in pregnant women. DESIGN: Prospective observational study. SETTING: Queen Charlotte's and Chelsea Hospital for Women. SUBJECTS: One hundred and twenty-two pregnant women from the antenatal population of Queen Charlotte's Hospital. METHODS: Evaluation was carried out according to the British Hypertension Society (BHS) Protocol. RESULTS: The mean difference between observer and device for systolic blood pressure was 3 (SD 4) mmHg. For diastolic blood pressure the difference was 5 (SD 6) mmHg for Phase IV (muffling of Korotkoff sound), and 4 (SD 4) mmHg for Phase V (disappearance of Korotkoff sound). According to the BHS grading criteria, the device reached a B grading for systolic blood pressure. B grading was also reached for diastolic blood pressure (Phase V) but grade C for diastolic blood pressure (Phase IV). The accuracy criteria stipulated by the Association for the Advancement of Medical Instrumentation (AAMI) were also met for both systolic and diastolic blood pressure. CONCLUSION: The SpaceLabs 90207, when compared with trained observers, is accurate in determining both systolic and diastolic blood pressure for clinical purposes, as judged by the BHS Protocol in pregnancy. PMID- 8217972 TI - Antiphospholipid antibodies in pregnancy: prevalence and clinical associations. AB - OBJECTIVE: To determine prevalence, clinical association and predictive power of antiphospholipid antibodies in pregnancy. DESIGN: To test for the presence of anticardiolipin antibodies and lupus anticoagulant in order to confirm prevalence data which imply that each antibody has the same clinical significance. A detailed obstetric history and the outcome measures were obtained from each patient in the study. SETTING: National Women's Hospital, Auckland, New Zealand. SUBJECTS: Nine hundred and thirty-three consecutively booked pregnant women. MAIN OUTCOME MEASURES: Prevalence of auto-antibodies; perinatal morbidity and mortality; incidence of pre-eclampsia, growth retardation and fetal distress. RESULTS: Nine women (1.0%) had anticardiolipin antibodies, 11 (1.2%) had lupus anticoagulant and two had both antibodies. The fetal mortality rate for women with antibodies was 167/1000. Pre-eclampsia occurred significantly more often in women with auto-antibodies. CONCLUSION: The presence of antiphospholipid antibodies is frequently associated with adverse pregnancy outcome (9/18 pregnancies). High titre anticardiolipin antibodies carry a poor prognosis. PMID- 8217973 TI - Second trimester ambulatory blood pressure in nulliparous pregnancy: a useful screening test for pre-eclampsia? AB - OBJECTIVE: To assess the effectiveness of second trimester 24-hour ambulatory blood pressure measurement as a screening test for pre-eclampsia. DESIGN: Prospective interventional study. SETTING: John Radcliffe Maternity Hospital, Oxford, and Queen Charlotte's and Chelsea Hospital, London. SUBJECTS: One hundred and sixty-two normotensive nulliparous women recruited at hospital booking clinics. INTERVENTION: Ambulatory blood pressure was measured at 18 and 28 weeks gestation using the TM2420 monitor. MAIN OUTCOME MEASURE: The development of pre eclampsia. RESULTS: Awake systolic and mean arterial pressures were significantly increased (P < 0.02) at 18 weeks in those who later developed pre-eclampsia. Those differences were more apparent at 28 weeks at which time the diastolic pressure was also increased (P < 0.01). At both stages of gestation the higher readings were sustained during sleep so that the awake-sleep differences were similar in relation to each outcome. The group with incipient pre-eclampsia had a significantly faster heart rate at both 18 and 28 weeks (P < 0.002) The sensitivity in predicting pre-eclampsia for a mean arterial pressure of 85 mmHg or greater at 28 weeks was 65%, with a positive predictive value of 31%. The sensitivity and positive predictive value for a test combining a mean arterial pressure of 85 mmHg or greater and a heart rate of 90 bpm or greater were 53% and 45%, respectively. CONCLUSION: Although second trimester ambulatory blood pressure is significantly increased in women who later develop pre-eclampsia, the predictive values for blood pressure alone are low. The efficiency of the test is increased by combining the awake ambulatory heart rate and blood pressure measurement together. If an effective method for preventing pre-eclampsia becomes available (commencing at 28 weeks gestation), then awake ambulatory blood pressure and heart rate may have some clinical value as a screening test. PMID- 8217974 TI - Urine production rate is related to behavioural states in the near term human fetus. AB - OBJECTIVE: To investigate the relation between hourly fetal urine production rate (HFUPR) and behavioural states 1F and 2F (corresponding to quiet and active sleep, respectively) in normal near term fetuses. DESIGN: An observational study. SETTING: A clinic for antenatal care at a university hospital. SUBJECTS: Nineteen healthy pregnant women examined at 37 to 40 weeks of gestation. MAIN OUTCOME MEASURES: Fetal behavioural states (1F and 2F) were assessed by means of fetal heart rate patterns (FHR A and FHR B). Using real time ultrasonography, HFUPR (ml/h) was estimated during behavioural states 1F and 2F. RESULTS: During behavioural state 1F, HFUPR was significantly higher than during state 2F (P < 0.01). HFUPR falls by 47% from 50.8 +/- 24.4 ml/h in state 1F to 25.7 +/- 15.0 ml/h in state 2F. CONCLUSIONS: During active sleep (state 2F) hourly fetal urine production rate is considerably reduced as compared to quiet sleep (state 1F). PMID- 8217975 TI - Anti-D concentrations in fetal and maternal serum and amniotic fluid in rhesus allo-immunised pregnancies. AB - OBJECTIVE: To investigate the relation between anti-D concentrations in maternal serum, fetal serum and amniotic fluid, and the development of fetal anaemia. DESIGN: Observational cross sectional and longitudinal study. SETTING: Regional referral centre. SUBJECTS: Sixty-one women undergoing fetal blood sampling at 19 to 36 weeks' gestation for fetal blood and haematocrit estimation for the management of Rh (D) allo-immunisation. Thirty-eight pregnancies (7 with an Rh (D) negative fetus) were tested only once but the rest had two to five fetal blood samplings. INTERVENTIONS: Ultrasound guided fetal blood sampling and amniocentesis, and automated analysis of anti-D antibody quantitation. RESULTS: There were strong correlations between maternal serum, fetal serum and amniotic fluid anti-D concentrations. Analyses of both longitudinal and cross sectional data demonstrated a decrease of the maternal/fetal serum anti-D ratio with gestation. In pregnancies with Rh (D) negative fetuses the maternal/fetal anti-D ratio was significantly lower (P < 0.0001) than in those with Rh (D) positive fetuses. The degree of fetal anaemia (delta haematocrit) was correlated with maternal serum and amniotic fluid anti-D concentrations (r = -0.55, n = 54, P < 0.0001; r = -0.57, n = 44, P < 0.0001, respectively) but there was a weaker correlation with fetal serum anti-D (r = 0.37, n = 54, P < 0.01). CONCLUSION: Anti-D concentrations in maternal serum, fetal serum and amniotic fluid are correlated with fetal anaemia. The decrease in maternal/fetal anti-D ratio with gestation suggests an increase in placental permeability for anti-D with advancing pregnancy. PMID- 8217976 TI - The adnexal mass: benign or malignant? Evaluation of a risk of malignancy index. AB - OBJECTIVE: To validate a risk of malignancy index incorporating menopausal status, serum CA 125 level and pelvic ultrasound features in the pre-operative diagnosis of ovarian cancer. DESIGN: A retrospective observational study. SETTING: Department of Obstetrics and Gynaecology, The Royal London Hospital. SUBJECTS: One hundred and twenty-four women admitted consecutively to the gynaecology department for surgical exploration of an adnexal mass. MAIN OUTCOME MEASURES: The sensitivities and specificities of menopausal status, serum CA 125 level and ultrasound features, in isolation and combined (the risk of malignancy index (RMI)), for diagnosing ovarian cancer. RESULTS: Tested on a new population of women, the RMI retained the high sensitivity for diagnosing ovarian cancer seen in the original report describing its derivation. The specificity, however, was lower. The study confirmed that the RMI is more accurate than the individual criteria in diagnosing ovarian cancer, and was comparable with other scoring systems. CONCLUSIONS: The risk of malignancy index is a simple scoring system for ovarian cancer. Application of the risk of malignancy index in clinical practice may provide a rational basis for specialist referral of patients with ovarian cancer before diagnostic surgery. PMID- 8217977 TI - Can laparoscopic assisted hysterectomy safely replace abdominal hysterectomy? AB - OBJECTIVE: To evaluate the feasibility, safety and advantages of laparoscopic hysterectomy. DESIGN: Retrospective review. SETTING: St. John of God Hospital, Perth, Australia. SUBJECTS: Fifty-four women scheduled to undergo laparoscopic hysterectomy for a variety of benign gynaecological conditions. MAIN OUTCOME MEASURES: Failure to complete the operation laparoscopically, time taken in theatre, incidence of febrile morbidity, incidence of major complications, duration of post-operative stay in hospital, interval from operation to full activity and return to work. RESULTS: Laparoscopic hysterectomy was attempted in 54 women. A total of 53 operations were completed laparoscopically with one conversion to laparotomy because of haemorrhage. Major complications occurred in two women, both of whom required further surgery. There were four cases of febrile morbidity. The average duration of post-operative stay was four days (range 2-9), with return to normal activity in two and a half weeks and to work in three weeks. CONCLUSIONS: Laparoscopic hysterectomy can be successfully achieved in most women selected for the procedure. Serious complications are inherent to some of the techniques used, but these can be overcome by modifications. Proper training and supervision in laparoscopic surgery is essential during the learning phase of the technique. There are considerable advantages to eligible women in terms of a rapid return to normal activities and work. PMID- 8217978 TI - A study of endometrial morphology in women who failed to conceive in a donor insemination programme. AB - OBJECTIVE: To examine the morphology of endometrium in women who failed to conceive after nine or more cycles of donor insemination treatment. DESIGN: Prospective study. SETTING: Jessop Hospital for Women, Sheffield. SUBJECTS: Two groups: twenty-six infertile women and a control group of eight fertile women. INTERVENTION: Endometrial biopsy specimens were obtained in the mid-luteal phase, timed precisely by the luteinising hormone surge. MAIN OUTCOME MEASURE: Morphological study of endometrial biopsy specimens by the use of traditional dating criteria and established morphometric techniques. RESULTS: Twelve biopsy specimens (42%) were found to be retarded. In addition, morphometric analysis revealed significant differences in the glandular component of the endometrium between the infertile and fertile groups. CONCLUSION: Endometrial defect leading to implantation failure may be an important underlying cause of failure to conceive after repeated attempts at donor insemination. The endometrium should be investigated in this group of women, and further attempts at donor insemination treatment should be offered only in conjunction with attempts to restore the normality of the endometrium. PMID- 8217979 TI - What is vestibular papillomatosis? A study of its prevalence, aetiology and natural history. AB - OBJECTIVES: To clarify the prevalence, aetiology, symptoms and natural history of vestibular papillomatosis. DESIGN: Study in two parts: 1. prevalence assessed by colposcopic examination of the vulva of unselected patients by one doctor (J.M.W.); 2. patients selected by clinical appearance as having vestibular papillomatosis (by J.M.W. and other doctors) assessed in a research clinic. SETTING: Outpatient genitourinary medicine clinic in South London. SUBJECTS: Part 1 study: 295 female clinic attenders; part 2 study: 18 women with clinical vestibular papillomatosis. MAIN OUTCOME MEASURES: Part 1 study: number of unselected patients found to have vestibular papillomatosis. Part 2 study: associated symptoms, histology, DNA hybridisation and polymerase chain reaction on vulval biopsies. Clinical regression of lesions. Cervical cytology and colposcopy. RESULTS: Part 1 study: Vestibular papillomatosis was identified by colposcopic examination of the vulva in 3/295 (1%) of women. Part 2 study: 9/18 (50%) women with vestibular papillomatosis were asymptomatic; the other nine had intermittent mild symptoms. Thirteen (72%) had a history of genital warts. Vulval biopsies had features suggestive of wart virus infection on histology in 17/18 (94%) and HPV16 was found by DNA hybridisation studies or polymerase chain reaction in 7/18 (39%). On follow up (mean duration 9 months) the vulval lesions had regressed in 9/12 patients. Ten patients had cervical wart virus infection or intraepithelial neoplasia (CIN), or both, and five needed laser treatment for this. CONCLUSIONS: In this study vestibular papillomatosis was associated with human papillomavirus (HPV) infection. This study suggests that vestibular papillomatosis need not be treated, but patients with it may be at increased risk for CIN. PMID- 8217980 TI - The effect of placental syncytiotrophoblast microvillous membranes from normal and pre-eclamptic women on the growth of endothelial cells in vitro. AB - OBJECTIVES: To determine if placental syncytiotrophoblast microvillous (STBM) membranes contain factors which could cause the maternal endothelial cell disturbance thought to be central to the pathophysiology of the maternal syndrome of pre-eclampsia. DESIGN: STMB membranes isolated from pre-eclamptic or normal placentae were added to cultures of endothelial cells and their effect on the proliferation (measured by 3H-thymidine incorporation), viability (measured by 51Cr release) and growth as a monolayer of these cells was determined. Membranes prepared from red blood cells, and non-endothelial adherent and nonadherent cell lines were used as specificity controls. SUBJECTS: STBM membranes were isolated from the placentae of primigravid women, 10 having caesarean sections for breech presentations and 10 for pre-eclampsia. RESULTS: STBM membranes from the placentae of normal and pre-eclamptic women suppressed endothelial cell proliferation to a similar extent and disrupted the cell monolayer to form a honeycomb-like pattern. This change in morphology was seen before significant endothelial cell death occurred. Red blood cell membranes had no effect on either endothelial cell proliferation, viability or monolayer integrity. Endothelial cells from human umbilical arteries and bovine adrenal capillaries were similarly suppressed, but comparable concentrations of STBM membranes had no effect on non endothelial cell lines. CONCLUSIONS: Syncytiotrophoblast microvillous membranes specifically interfered with endothelial cell growth in vitro. Our results demonstrate that there are trophoblast products which could cause the maternal syndrome of pre-eclampsia through endothelial cell damage. PMID- 8217981 TI - Invasive hydatidiform mole presenting as an acute primary haemoperitoneum. PMID- 8217982 TI - Postpartum rupture of the spleen. PMID- 8217983 TI - Refractory rhesus (D) disease. PMID- 8217984 TI - Acute pancreatitis with pseudocyst formation complicating pregnancy in a patient with a co-existent choledochal cyst. PMID- 8217985 TI - Severe hypotension and fetal distress following sublingual administration of nifedipine to a patient with severe pregnancy induced hypertension at 33 weeks. PMID- 8217986 TI - Monitoring the fetus with a sensor covered with an irregular surface can cause scalp ulceration. PMID- 8217987 TI - Endometriosis of the rectum. PMID- 8217988 TI - LLETZ and infertility. PMID- 8217989 TI - The effect of a new sequential oestradiol valerate and levonorgestrel preparation on the bone mineral density of postmenopausal women. PMID- 8217990 TI - The role of trophoblast dysfunction in the aetiology of miscarriage. PMID- 8217991 TI - Measurement of uterine activity in labour--clinical aspects. PMID- 8217992 TI - Chirality in the umbilical cord. PMID- 8217994 TI - National Perinatal Epidemiology Unit--a national asset. PMID- 8217993 TI - Should we try to supplement the growth retarded fetus? A cautionary tale. PMID- 8217995 TI - The Read clinical classification. PMID- 8217996 TI - False negative cervical smears. PMID- 8217997 TI - Recent advances in the treatment of carcinoma of the ovary. PMID- 8217998 TI - Reagent strip testing of antenatal urine specimens for infection. AB - OBJECTIVE: To compare reagent strip testing (RST) with microscopy and culture in identifying significant bacteriuria, and secondly, to consider potential cost savings if RST screening proved to be reliable. DESIGN: Prospective descriptive study. SETTING: Antenatal Clinic, Bristol Maternity Hospital. SUBJECTS: Eight hundred and ninety-eight women having urine testing in pregnancy for microscopy and culture either routinely or because of a clinical infection. INTERVENTIONS: The midstream specimens of urine had RST examination using Ames Multistix 8SG prior to being sent to the laboratory. MAIN OUTCOME MEASURE: Significant culture (> 10(5) colonies/ml) of a single organism in culture. RESULTS: The highest predictive value for a negative result of the urine culture (99.7%) was obtained when using four RSTs in combination. The RST for nitrite had a high predictive value for a positive urine culture (90%). The samples which gave a false negative result with RST screening were mainly infected with low grade urinary pathogens or genital tract contaminants. CONCLUSION: RST screening for bacteriuria provides a reliable and cheap alternative to culture of all urine specimens. PMID- 8217999 TI - Low dose aspirin in hypertensive pregnant women: effect on pregnancy outcome and prostacyclin-thromboxane balance in mother and newborn. AB - OBJECTIVE: To study the effect of daily treatment with 50 mg of aspirin (ASA) on the hypertensive pregnancy complications and on the production prostacyclin (PGI2) and thromboxane A2 (TxA2) in high risk pregnant women and their infants. DESIGN: Placebo controlled prospective study. SETTING: Departments of Obstetrics and Gynaecology, University of Helsinki, University of Oulu and Central Hospital of Middle Finland, Finland. SUBJECTS: Two hundred and eight pregnant women with pre-existing hypertension or a history of severe preeclampsia in their previous pregnancy. Prostanoids were studied in a subgroup of 18 women. INTERVENTIONS: The women were randomised to receive ASA (50 mg/day, n = 103) or placebo (n = 105) from the mean of 15 weeks gestational age to delivery. The exacerbation of pre existing hypertension or the appearance of hypertension in previously normotensive women, the appearance of proteinuria and fetal growth were the main end points, but some other clinical characteristics were also recorded. Urinary excretion of PGI2 and TxA2 metabolites by mothers and infants and their production in umbilical arteries in vitro were also studied. RESULTS: Two women (one in both groups) had miscarriages, and one pregnancy was terminated for fetal anencephaly (ASA group). In addition, seven women discontinued the treatment due to urticaria (two women in ASA group), increased activity of aspartate amino transferase in serum (one woman in both groups), or increased bleeding time (one woman in ASA group, two women in placebo group), and one woman in the placebo group was lost from follow-up. Thus the end points could be assessed in 97 women taking ASA and 100 women taking placebo. ASA did not diminish the rate of the rise of blood pressure without (12 vs 14, respectively) or with proteinuria (9 vs 11), but fetal haemodynamic disturbances as assessed by Doppler equipment (1/44 vs 6/45 women studied, P = 0.05) and need for treatment in neonatal intensive care unit (10 vs 21, P = 0.04) were more rare in ASA group. ASA tended to increase the birthweight of the newborn (3348 +/- 707 g vs 3170 +/- 665 g, mean +/- SD, P = 0.07), but two perinatal deaths occurred in ASA group. ASA prolonged the bleeding time of the mother (435 s, 210-998 s (geometric mean, range) vs 349 s, 210-690 s, P = 0.02), but caused no extra blood loss during delivery, nor affected neonatal hemostasis. In a subgroup of mothers (ASA, n = 10; placebo, n = 8), ASA inhibited more than 90% of platelet TxA2-production, and caused a 65 to 80% decrease in the urinary excretion of TxA2 metabolites, but no decrease in the urinary excretion of PGI2 metabolites. CONCLUSIONS: ASA did not prevent the rise of maternal hypertension, but improved fetal haemodynamic performance and reduced the need of intensive neonatal care. It inhibited strongly maternal thromboxane A2 but not PGI2 production and thus shifted the balance between PGI2/TxA2 to the dominance of the vasodilatory, anti-aggregatory side. PMID- 8218000 TI - Longitudinal assessment of amniotic fluid index. AB - OBJECTIVE: To derive a longitudinal gestational reference range for amniotic fluid index and to compare it with the established cross-sectional reference range. DESIGN: Longitudinal prospective study. SETTING: Liverpool Maternity Hospital and Mill Road Maternity Hospital, both teaching hospitals in central Liverpool. SUBJECTS: One hundred and fifteen pregnant women, in whom the expected date by the last menstrual period and ultrasound scan at 18 to 19 weeks were in agreement by seven days, were recruited. They were divided into two groups and scanned at four weekly intervals as follows: Group A: scanned at 20, 24, 28, 32, 36, 40; and Group B: scanned at 22, 26, 30, 34, 38, 42. RESULTS: Amniotic fluid index varies with gestation, rising from early gestation to peak at 30 weeks and then falling from 36 to 42 weeks. Comparison of our reference range with that of Moore and Cayle (1990) shows obvious differences at the lower limit. CONCLUSION: We have established a normal longitudinal reference range for the amniotic fluid index. Our ranges, derived from longitudinal data, would seem a more appropriate reference than the established reference ranges derived from cross-sectional data. In particular, the differences at the lower limits may have considerable clinical implication in the use of amniotic fluid index in the prediction of fetal compromise. PMID- 8218001 TI - An audit of the obstetric outcome of 148 consecutive pregnancies from assisted conception: implications for neonatal services. AB - OBJECTIVE: To assess the outcome of pregnancy following assisted conception. DESIGN: Cohort descriptive study. SETTING: Unit of Reproductive Medicine, Ninewells Hospital and Medical School. SUBJECTS: One hundred and forty-eight consecutive assisted conceptions. MAIN OUTCOME MEASURES: Patient characteristics and outcome of pregnancy. RESULTS: Seventy-nine percent of mothers were aged between 26 and 35 years (mean 31.4). The main causes of infertility were tubal (48%), unexplained (35%), anovulatory (8%) and male factor (8%). Primary infertility accounted for 61% of cases and 82% of pregnancies occurred within 3 treatment cycles. Thirty-five (24%) pregnancies miscarried before 14 weeks and 7 (5%) between 15 and 24 weeks gestation. One hundred and three pregnancies resulted in 136 liveborn infants. There was one neonatal death. Thirty-five babies were admitted to SCBU. Antenatally, 13% of patients were admitted to hospital with hypertension and 8% with APH; 50% of multiple and 13% of singleton pregnancies were delivered prematurely, 68% following preterm labour. There were 28 sets of twins (four miscarried at less than 24 weeks) and four sets of triplets. Multiple pregnancy was not associated with cause of infertility, treatment, age or ovarian hyperstimulation syndrome. Seventy-eight per cent of singletons and 50% of multipara were delivered vaginally. CONCLUSIONS: Our data confirm the high incidence of pregnancy loss and preterm delivery associated with assisted conception once allowing for the high rate of multiple pregnancies. The effect of assisted conception programme on health services is discussed. PMID- 8218002 TI - Increased risk of aneuploidy in women having unsuccessful chorionic villus sampling procedures. AB - OBJECTIVE: To determine the incidence of fetal aneuploidy in women who had unsuccessful chorionic villus sampling (CVS) procedures. DESIGN: Retrospective study. SETTING: Pennsylvania Hospital, Philadelphia, Pennsylvania, USA. SUBJECTS: Two thousand six hundred and sixty-eight women who underwent chorionic villus sampling, in 78 (2.9%) of whom villi could not be obtained. INTERVENTIONS: Sixty nine of 78 (88%) women who had an unsuccessful CVS procedure underwent a subsequent amniocentesis later in the same pregnancy. MAIN OUTCOME MEASURES: The incidence of aneuploidy identified from amniotic fluid chromosome analysis in the 69 women who had an unsuccessful CVS procedure compared to the frequency of aneuploidy in women having a successful CVS procedure. RESULTS: Of the 69 women who underwent a post-CVS amniocentesis because of failure to obtain chorionic villi, six aneuploid pregnancies were identified (8.7%). The frequency of aneuploidy in the 2590 successfully sampled CVS patients was 2.5%. This difference was statistically significant (P = 0.009) by Fisher's exact test (two tailed). CONCLUSIONS: Women having an unsuccessful CVS procedure should be informed that they may be at increased risk for carrying an aneuploid fetus. PMID- 8218003 TI - The effect of cordocentesis on umbilical and middle cerebral artery blood flow velocity waveforms. AB - OBJECTIVE: To investigate the effect of cordocentesis on the umbilical and fetal cerebral circulation. DESIGN: Cross sectional study. SETTING: Department of Obstetrics and Gynaecology, Regional Referral Centre for Fetal Medicine, Klagenfurt Hospital, Austria. SUBJECTS: Thirty pregnant women undergoing diagnostic cordocentesis at 18 to 38 weeks' gestation. INTERVENTIONS: The pulsatility index (PI) in the umbilical artery and fetal middle cerebral artery was measured by pulsed Doppler ultrasound before and immediately after cordocentesis. MAIN OUTCOME MEASURES: Change in umbilical artery PI and middle cerebral artery PI. RESULTS: Cordocentesis was associated with a significant decrease in both umbilical artery PI (median -0.18, range -2.21 to 1.5, P < 0.004) and middle cerebral artery PI (mean -0.15, SD 0.32, P < 0.03) and the decrease in umbilical artery PI was most marked when cordocentesis was performed transplacentally. In four cases, there were absent or reversed frequencies at the end of diastole (EDF) in the umbilical artery before cordocentesis, and in all cases there were positive EDF after the procedure. In contrast, one of the 26 cases with positive EDF developed reversed EDF following the procedure. CONCLUSIONS: Acute alterations in the waveforms from both the umbilical and fetal cerebral circulation can be induced by cordocentesis. The decrease in resistance in the fetoplacental circulation could be attributed to the release of vasodilators, and the increase in resistance observed in some cases could be secondary to arterial vasospasm. Better understanding of the underlying mechanisms might help in making cordocentesis a safer procedure. PMID- 8218005 TI - Stereomicroscopic demonstration of chorionic villi: differentiation between miscarriage and ectopic pregnancy. AB - OBJECTIVE: To evaluate direct peroperative stereomicroscopic examination of endometrial curettings in the differentiation between miscarriage and ectopic pregnancy. DESIGN: A prospective consecutive controlled study. SETTING: Odense University Hospital, Odense, Denmark. SUBJECTS: One hundred and fifty-nine women with vaginal bleeding and/or abdominal pain in early pregnancy and no fetus seen on ultrasound. MAIN OUTCOME MEASURES: The results of stereomicroscopy were compared with the histological diagnoses. RESULTS: There was 90% (95% CI, 84-94%) agreement between the stereomicroscopic and histological examinations. Fifteen per cent had an ectopic pregnancy. The sensitivity of stereomicroscopy as a marker of ectopic pregnancy was 92% (73-99%), the specificity 94% (88-97%). The predictive value of a positive test was 73% (54-88%) and that of a negative test 98% (94-100%). CONCLUSION: Direct peroperative stereomicroscopy of endometrial curettings is a valuable diagnostic tool for immediate differentiation between miscarriage and ectopic pregnancy. PMID- 8218004 TI - Comparative profiles of reliability, cycle control and side effects of two oral contraceptive formulations containing 150 micrograms desogestrel and either 30 micrograms or 20 micrograms ethinyl oestradiol. AB - OBJECTIVE: To compare two oral contraceptive pills, both containing 150 micrograms desogestrel, but with either 20 micrograms (Mercilon) or 30 micrograms (Marvelon/Desolett) ethinyl oestradiol (EE), regarding reliability, cycle control and side effect profile. DESIGN: A double blind, randomised, multicentre study over one year with follow up after three, six and 12 months. The women noted tablet intake and all bleedings on specifically designed diary cards. SETTING: University clinics, central hospitals and private gynaecological practices in Norway, Sweden and Denmark. SUBJECTS: One thousand women aged 18 to 40 years requesting oral contraceptive pills. MAIN OUTCOME MEASURES: Reliability, cycle control, side effects, blood pressure, body weight and haemoglobin. RESULTS: In a total of 4543 cycles with the 20 micrograms EE dose pill and 4688 cycles with the 30 micrograms EE dose pill, the number of pregnancies ascribed to method failure were 0 and 2, respectively. Irregular bleeding (break-through bleeding or spotting) was significantly more frequent with the 150/20 combination in about two-thirds of the cycles randomly distributed over the one year of the study. Mean blood pressure decreased slightly, particularly in the group on the 150/20 combination (about 1 mmHg), whereas mean body weight increased approximately 0.5 kg in the group with the 150/30 combination after 12 months. Haemoglobin did not change. Side effects other than bleeding problems were rare, but dizziness and mood changes were more frequent in the group on the 150/20 combination. Due to side effects, more women on the 150/20 combination discontinued the study during the one to three and four to six month periods, and women on this pill were also less positive about continuing the study drug at the end of the trial. CONCLUSIONS: Both pills have high contraceptive reliability and are well tolerated, but with the 150/20 combination the cycle control is less effective. However, in view of the potentially increased safety profile of the 150/20 combination, many women can be expected to accept some additional discomfort due to irregular bleeding. PMID- 8218006 TI - The assessment of clinical competence in obstetrics and gynaecology in two medical schools by an objective structured clinical examination. AB - OBJECTIVE: To compare and assess clinical competence among final year students in two British medical schools using a standardised objective structured clinical examination (OSCE) in obstetrics and gynaecology. DESIGN: A comparative study of an OSCE with stations designed to test student abilities in history-taking, physical examination, interpretation of data or results, interpersonal skills, practical procedures, as well as factual knowledge. SUBJECTS: Two groups of final year medical students from two British medical schools. METHODS: An OSCE of 26 stations. RESULTS: The standardised OSCE was simple to organise and conduct once the content had been decided. Analysis of the results revealed significant differences in mean marks between the two sets of students in six stations, and in eight stations the mean score was less than five for one or other sets of students. The reasons for the differences between the medical schools and the poor performance of the students at some stations were investigated and possible causative factors identified. CONCLUSIONS: We have shown that an OSCE is suitable for testing clinical competence of students within and across medical schools, is able to highlight differences in standards between institutions, and can identify areas where teaching methods and/or course content are deficient. PMID- 8218007 TI - Low levels of amniotic fluid placental alkaline phosphatase in Down's syndrome. AB - OBJECTIVE: To investigate amniotic fluid placental alkaline phosphatase (PLAP) levels in normal and trisomy 21 pregnancies. DESIGN: Cross sectional study. SETTING: A tertiary referral prenatal diagnostic service. SUBJECTS: Three hundred and eleven women with singleton pregnancies of normal karyotype between 10 and 23 weeks gestation and 31 women with pregnancies associated with trisomy 21 Down's syndrome. OUTCOME MEASURES: PLAP levels were measured by immunoradiometric assay in amniotic fluid obtained by amniocentesis. RESULTS: Amniotic fluid PLAP was detectable from 12 weeks gestation and the median value rose to a peak of 4.57 iu/l at 18 weeks. Pregnancies associated with Down's syndrome had significantly lower levels with a median multiple of median (MoM) of 0.638, (U = 3374, P = 0.0016, 95% CI = 0.50, 0.89). For the 20 women with trisomy 21 pregnancies detected at 16 to 18 weeks, the median MoM was 0.482, (U = 3694, P = 0.0011, 95% CI = 0.37, 0.85). CONCLUSION: These data demonstrates that PLAP levels are reduced in the amniotic fluid of women carrying a fetus with trisomy 21. PMID- 8218008 TI - Plasma protein levels in normal human fetuses: 13 to 41 weeks' gestation. AB - OBJECTIVES: To establish reference ranges for the levels of alpha-fetoprotein, albumin, prealbumin (transthyretin) alpha-1-antitrypsin, transferrin, ceruloplasmin and total protein in the plasma of normal human fetuses and newborn babies. DESIGN: Prospective study of individual normal cases to fulfil objectives. SETTING: Pathology laboratories of the University of Edinburgh and the biochemistry laboratories of the University of Keele. SUBJECTS: Twenty-two normal fetuses 13 to 22 weeks of gestation and 66 babies born between 24 and 41 weeks gestation. RESULTS: Albumin is the predominant plasma protein throughout gestation. The levels of alpha-fetoprotein and prealbumin fell significantly with increasing gestation, whereas the concentrations of the other proteins studied increased. The ratios of individual proteins to total protein demonstrated similar trends. CONCLUSIONS: This study provides developmental profiles of normal human fetal plasma proteins to serve as possible reference data for abnormal fetuses. Declining levels of prealbumin (transthyretin) were unexpected and suggest a functional role for this protein in early pregnancy. PMID- 8218009 TI - Repair of prolapse by means of a living ligament. PMID- 8218010 TI - Primary volvulus of the small bowel following normal delivery. PMID- 8218011 TI - Unilateral dysmenorrhoea due to an haematometra in a rudimentary horn. PMID- 8218012 TI - Placental bands: a variant of placenta praevia? PMID- 8218013 TI - Adverse cardiovascular sequelae of ergometrine. PMID- 8218014 TI - Persistent menorrhagia despite total absence of endometrium. PMID- 8218015 TI - Twin pregnancy consisting of a complete hydatidiform mole and a fetus: genetic origin determined by DNA typing. PMID- 8218016 TI - High resolution ultrasound in the diagnosis of heterotopic pregnancy: combined transabdominal and transvaginal approach. PMID- 8218017 TI - Faecal carriage of listeria during pregnancy. PMID- 8218018 TI - The effect of oxytocics stored at high temperatures on postpartum uterine activity. PMID- 8218019 TI - Serum screening for Down's syndrome. PMID- 8218020 TI - The recruitment of oocyte donors. PMID- 8218021 TI - Management and outcome of obstructive uropathy in twin pregnancies. PMID- 8218022 TI - Dose and time dependent rise of plasma cortisol following administration of mifepristone in early pregnancy. PMID- 8218023 TI - The loss of a baby at birth: the role of the bereavement officer. PMID- 8218024 TI - The role of research in the training of an obstetrician and gynaecologist. PMID- 8218025 TI - The role of research in the training of an obstetrician and gynaecologist. PMID- 8218026 TI - The role or research in the training of an obstetrician and gynaecologist. PMID- 8218027 TI - Local resection of choroidal melanoma. PMID- 8218028 TI - Predictive factors of visual outcome after local resection of choroidal melanoma. AB - Local resection of choroidal melanomas is not widely performed so that the indications for this operation have not previously been defined statistically. Univariate and multivariate Cox regression analyses were used to identify the factors influencing visual acuity after 163 completed local resections for choroidal melanoma in patients with a preoperative visual acuity of counting fingers or better. The variables included in the analyses were patient age and sex; eye laterality and preoperative visual acuity; location of anterior and posterior tumour margins; tumour location (coronal and sagittal); tumour diameter, thickness, and cell type; ocular decompression by vitrectomy; and adequacy of surgical clearance. The surgical resections were performed using a lamellar scleral flap for eye closure, hypotensive anaesthesia for haemostasis, and, in the later years, ocular decompression by pars plana vitrectomy to improve access. The patients (94 men, 69 women) had a mean age of 50 years. The tumours had a mean diameter of 13.3 mm and a mean thickness of 7.4 mm, with 38 tumours extending to within 1 disc diameter (DD) of the optic disc, fovea or both (that is, 'posterior tumour extension'). Cox multivariate analysis showed that the most significant preoperative factors for predicting retention of good vision (6/12 or better) were nasal tumour location (p = 0.002) and distance of more than 1 DD between the tumour and the optic disc or fovea (p = 0.010). The most significant predictive risk factor for severe visual loss (hand movements or worse) was posterior tumour extension to within 1 DD of the optic disc and/or fovea (p = 0.009). One year post-operatively, all 28 patients with nasal tumours not extending to within 1 DD of the optic disc or fovea retained the eye with 57% having vision of 6/12 or better and 93% having vision of counting fingers or better. In 68 patients with temporal tumours, 90% retained the eye at 1 year with preservation of vision of counting fingers or better in 82% of 56 eyes without posterior tumours extension and in 50% of 12 eyes with posterior tumour extension. In patients with choroidal melanoma, conservation of the eye and vision can be achieved by local resection, especially if the tumour is located nasally and does not extend close to the disc or fovea. PMID- 8218029 TI - Clinical predictive factors for development of recurrence and metastasis in conjunctival melanoma: a review of 68 cases. AB - Sixty eight cases of histologically proved conjunctival melanoma were reviewed in order to determine the clinical factors that were predictive of local recurrence and distant metastasis. All patients were treated with surgical excision and most had supplemental cryotherapy. The mean follow up was 7.5 years. Histopathologically, the conjunctival melanoma arose from primary acquired melanosis in 56%, from naevus in 26%, and de novo in 18%. Of the 68 patients, 38 (56%) developed at least one local tumour recurrence and 22 (32%) developed more than one recurrence. The method of initial treatment and the eventual development of metastasis were the two parameters statistically associated with tumour recurrence. Those patients treated initially with tumour excision alone had a statistically significant higher recurrence rate than those treated initially with excision and supplemental cryotherapy (p = 0.001). Fourteen patients (21%) developed metastasis and the mean period between treatment and metastasis was 3.6 years. Twelve (18%) died from metastatic melanoma with a mean interval of 4.4 years from the time of initial surgery until death. The only clinical parameter that was statistically associated with distant metastasis was local tumour recurrence (p = 0.015). Based on these observations, the authors make recommendations regarding the treatment of conjunctival malignant melanoma. It appears that initial complete excision of the tumour with supplemental cryotherapy offers the patient the best chance of remaining free of recurrence and metastasis. PMID- 8218030 TI - Post-traumatic angle recession glaucoma: a risk factor for bleb failure after trabeculectomy. AB - In order to determine if post-traumatic angle recession is a risk factor for failure of glaucoma filtering surgery independent of age or race, the surgical results of trabeculectomy performed in 35 consecutive patients with angle recession glaucoma were compared with those of 35 matched patients with primary open angle glaucoma. A postoperative intraocular pressure of < or = 21 mm Hg (with or without glaucoma medication) was found in 15 of the 35 (43%) patients with angle recession glaucoma compared with 26 of the 35 (74%) patients with primary open angle glaucoma. The long term success of trabeculectomy was significantly worse in angle recession glaucoma when the results were analysed using Kaplan-Meier survival curves. Bleb failure occurred a mean period of 3.1 (SD 1.2) months after trabeculectomy in angle recession glaucoma compared with 9.4 (5) months in primary open angle glaucoma (p < or = 0.001). The finding that posttraumatic angle recession is a risk factor for failure of trabeculectomy, supports the use of antimetabolite therapy to suppress fibrosis after trabeculectomy in these patients. PMID- 8218031 TI - Spontaneous hyphema associated with anterior uveitis. AB - Few reports have described hyphema in association with anterior uveitis. Five cases of anterior chamber haemorrhage are reported in patients with five different anterior uveitic entities: Reiter's syndrome, juvenile chronic arthritis, ankylosing spondylitis, idiopathic anterior uveitis, and herpes simplex. Hyphema has been reported in association with idiopathic non granulomatous anterior uveitis, but not with the other four entities. In three cases, iris rubeosis was present. In two cases the patients were taking non steroidal anti-inflammatory agents. The hyphemas occurred at times of heightened inflammation and resolved spontaneously without complication in all but one case, a boy with idiopathic uveitis who required surgery to remove the blood. The clinical outcome of these cases provides evidence that conservative medical management is usually sufficient. PMID- 8218032 TI - The fixed dilated pupil after cataract surgery--is it related to intraocular use of hypromellose? AB - Hypromellose can be used as a viscoelastic substance during cataract surgery. Two groups of patients, one group operated on using hypromellose, the other using sodium hyaluronate as a viscoelastic substance were followed up 2-6 months postoperatively. A total of 16.7% of the eyes operated on using hypromellose developed a non-reactive semidilated pupil whereas none of the eyes from the control group developed this phenomenon. It was concluded that there is a probable link between the intraocular use of hypromellose and abnormal pupils after cataract surgery. PMID- 8218033 TI - Ophthalmic features and visual prognosis in the Treacher-Collins syndrome. AB - The ocular findings and visual prognosis were reviewed in 24 patients with the Treacher-Collins syndrome who were evaluated in the craniofacial clinic in the Division of Pediatric Ophthalmology at Children's Hospital of Philadelphia between 1980 and 1991. All patients had some abnormality. Vision loss was present in 37% of patients. Amblyopia was present in 33%, significant refractive errors were present in 58%, and anisometropia was documented in 17%. Strabismus was present in 37% and significant lid and adnexal abnormalities were seen in 96%. The prognosis for normal vision in at least one eye is good but vision loss secondary to amblyopia is more resistant to treatment owing to other medical problems and social concerns. PMID- 8218034 TI - Ocular fundus in neurofibromatosis type 2. AB - Several ocular findings have been associated with neurofibromatosis type 2 (NF 2) since the identification of this disease as a distinct clinical entity. Juvenile cataracts were reported first, followed by combined pigment epithelial and retinal hamartomas. In a recent report, epiretinal membranes were described in seven of nine patients. Moreover, an association between NF 2 and optic disc gliomas has been suggested based on earlier published reports. Six patients with a confirmed diagnosis of NF 2 were examined. Four patients (six of 12 eyes) had epiretinal membranes and one had an optic disc glioma. In addition, one case of an optic disc glioma in a patient with NF 2 was tracked. It is concluded that epiretinal membranes are frequent in NF 2, and that optic disc glioma is a rare but specific sign of NF 2. Patients at risk for development of this disease should undergo careful examination of the ocular fundus. PMID- 8218035 TI - Corneal transplantation in the United Kingdom and Republic of Ireland. AB - The Corneal Transplant Follow up Study has registered 4560 corneal grafts performed in the United Kingdom and Republic of Ireland from July 1987 to June 1991. Rates of reported grafts doubled during that time. This increase was greater for surgeons and regions reporting fewer grafts, but was consistent across patient factors. Eleven of 428 consultants were responsible for over 25% of grafts, and their patients' characteristics differed significantly from others. Overall, reasons for grafting were visual only (77%), visual and other (16%), and non-visual (7%). Most frequent diagnoses were endothelial failure (38%), inflammation (26%), and keratoconus (20%). Age ranged from 2 months to 97 years, and differed markedly with diagnosis. Eighteen per cent of transplants were regrafts, and 40% were vascularised preoperatively. PMID- 8218036 TI - On manual dexterity. PMID- 8218037 TI - Early stages of age-related macular degeneration: an immunofluorescence and electron microscopy study. AB - In subretinal neovascularisation capillaries originating from the choriocapillaris must cross Bruch's membrane to reach the subretinal pigment epithelial space. Thus gaps in Bruch's membrane have to be formed before subretinal neovascularisation. Histological examination of eyes with subretinal neovascularisation or disciform scars has shown macrophages adjacent to thin areas and ruptures in Bruch's membrane. This has been interpreted as phagocytosis of Bruch's membrane. The purpose of this study was to investigate whether immune complex depositions can be detected in maculae with early stages of age-related macular degeneration and to explain the macrophage reaction before the disciform reaction. A series of 20 human maculae were examined by direct immunofluorescence light microscopy to detect the presence of immune complexes with antibodies directed against immunoglobulins, fibrinogen, and complement factors. Transmission electron microscopy on several maculae was performed to identify the macrophages. Macrophages were observed in close relation to the readily recognisable long spacing collagen, which suggested that long spacing collagen was selectively internalised by these cells. Definite immune complex depositions were not found in basal laminar deposits or drusen. Linear deposits of fibrinogen and complement were frequently found in the outer collagenous zone of Bruch's membrane. However, because of the absence of immunoglobulins, it seems unlikely that these non-specific deposits might cause chemoattraction of macrophages and play a role in the initial phase of the development of subretinal neovascularisation and disciform macular degeneration. PMID- 8218040 TI - Orbital masquerade: hyperthyroidism and cavernous haemangioma of the orbit. PMID- 8218039 TI - Bilateral optic neuropathy and white dot syndrome following a mycoplasmal infection. PMID- 8218038 TI - Clinical and genetic patterns of neurofibromatosis 1 and 2. PMID- 8218041 TI - Slow accommodation release with a cerebellar lesion. PMID- 8218042 TI - Neurotrophic keratitis presenting in infancy with involvement of the motor component of the trigeminal nerve. PMID- 8218043 TI - Cystoid macular oedema after excimer laser photoreactive keratectomy. PMID- 8218044 TI - Thymoxamine in the treatment of traumatic mydriasis. PMID- 8218045 TI - Fluorescein flushing of the forearm. PMID- 8218046 TI - Factors influencing metastasis in retinoblastoma. PMID- 8218047 TI - Anaesthesia for ophthalmic surgery. PMID- 8218048 TI - Choroidal invasion of retinoblastoma: metastatic potential and clinical risk factors. AB - There is considerable debate about the significance of choroidal invasion of retinoblastoma with regard to metastatic disease. The charts of patients with retinoblastoma were reviewed over a 17 year period to determine the frequency of histopathological choroidal invasion of retinoblastoma and its risk for eventual metastatic disease. Sixty seven of 289 eyes (23%) enucleated for retinoblastoma had histopathological evidence of choroidal invasion. Those patients with choroidal invasion (with or without optic nerve invasion) were more likely to develop metastases than those without choroidal invasion (p = 0.0001). When considering those patients with isolated choroidal invasion of retinoblastoma, excluding those with associated optic nerve invasion, there was no significant risk but there was a trend towards the development of metastases (p = 0.10). The clinical factors found to be predictive for choroidal invasion from retinoblastoma from a univariate analysis included increased intraocular pressure (p = 0.04) and iris neovascularisation (p = 0.007) and, from a multivariate analysis, iris neovascularisation (p = 0.02). The histopathological factors statistically associated with choroidal invasion included the presence of optic nerve invasion (p = 0.002) and poorly differentiated retinoblastoma (p = 0.003). Factors not predictive for choroidal invasion included the age, race, and sex of the patient and the tumour laterality, inheritance, size, and growth pattern. Choroidal invasion of retinoblastoma is a risk for metastases, especially if it is associated with any degree of optic nerve invasion. PMID- 8218049 TI - Symptomatic abnormalities of dark adaptation in patients with age-related Bruch's membrane change. AB - Some patients with age-related changes at the level of Bruch's membrane and good visual acuity report poor vision in dim light, fading vision in bright light, and a central scotoma noticeable in the dark. Ophthalmic examination, scotopic thresholds, and dark adaptation kinetics were recorded in 12 eyes of 12 patients with such symptoms. All had macular drusen which were hypofluorescent on fluorescein angiography in nine subjects, and six had evidence of prolonged choroidal filling on fluorescein angiography. Scotopic thresholds were depressed in six patients who all experienced a central scotoma in the dark or poor night vision. The kinetics of dark adaptation were abnormal in all 10 patients in whom reliable measurements were possible. The findings suggest that visual symptoms reflect abnormality of both scotopic sensitivity and the time course of dark adaptation in patients with age-related Bruch's membrane change. PMID- 8218050 TI - Stage III macular hole surgery. AB - Twelve macular holes in 12 patients underwent a pars plana vitrectomy and epiretinal membrane resection with intravitreal gas tamponade for repair of their macular holes. The patients had stage III macular holes and had previously undergone a normal funduscopic examination within 2 years. The patients have been followed for a mean of 14 months (range 12-18 months) postoperatively. The results show that visual acuity improvements were not seen until at least 6 months after surgery if the hole was closed successfully. Seven holes were closed (58.3%) and all improved their best corrected visual acuity by more than two Snellen lines. In the five eyes that did not demonstrate hole closure (41.6%), one eye improved by two lines as well. The other four eyes remained at their preoperative acuity. One eye developed a dialysis which responded to a fluid air exchange and cryopexy (8.3%). Three eyes developed minimal lenticular opacities during the follow up period (25%). One eye demonstrated an altered perifoveal pigment epithelium perhaps related to intraoperative light toxicity. Macular hole surgery can restore some central acuity even in patients with longstanding holes. PMID- 8218051 TI - Diode laser for retinopathy of prematurity--early outcome. AB - Diode laser treatment for retinopathy of prematurity was successful in 81% of 21 eyes with 'threshold' (zone 2, stage 3+) disease. This compares favourably with cryotherapy and argon laser photocoagulation. The retinal outcome and technique are discussed. PMID- 8218052 TI - Dissociated eye movements in craniosynostosis: a hypothesis revived. AB - A characteristic pattern of dissociated eye movements was observed in a large proportion of our patients with a variety of craniosynostosis syndromes. These anomalies simulate overaction of the inferior oblique and underaction of the superior oblique muscles which, however, cannot fully explain the abnormalities. In a number of cases, excyclorotation of the muscle cone was observed, with the upper pole of the eye tilted away from the midline. It is postulated that such excyclorotation of the eyes will lead to dissociated eye movements which can be explained on physiological grounds according to Hering's law. This paper presents a review of our patients and evidence to support this hypothesis. PMID- 8218053 TI - The invention of spectacles. PMID- 8218054 TI - Limbal and corneal calcification in patients with chronic renal failure. AB - In patients with chronic renal failure on regular dialysis treatment, limboconjunctival degenerations and calcifications are commonly observed. In this study three groups of patients were followed over a period of 6 years. The first group consisted of 47 patients with renal failure, the second group of 17 patients with renal failure and hyperparathyroidism not controlled by drugs, and the third group seven patients with primary hyperparathyroidism without renal failure. The aim of this study was to determine the progression of the limboconjunctival changes over time. The hypothesis that an increase in serum calcium and phosphorus concentrations, as a result of tertiary hyperparathyroidism, could possibly add a corneal component to the limbal calcification was also tested. All patients with renal failure (in as much as the degenerative limbal features were not obscured by deposits of lime salts), had a type II white limbus girdle of Vogt. This limbal degeneration was observed in only 45% of controls. In all 47 patients with renal failure conjunctival calcification was observed; 26 of them also had limbal calcification. After 6 years 41 patients had developed limbal calcification. This progression was statistically significant. In 15 out of 17 patients with tertiary hyperparathyroidism a band-shaped keratopathy developed in addition to the limboconjunctival calcification. PMID- 8218055 TI - Prevention of intraocular pressure rise following intravitreal injection. AB - The intraocular pressure change produced by an intravitreal injection of ganciclovir, 2 mg in 0.1 ml, was studied in patients with cytomegalovirus retinitis. Using a Tono-pen XL to measure the intraocular pressure (IOP) of four patients (six eyes) we found the mean pressure immediately following injection was 44.5 mm Hg. Measurements taken on separate occasions after a 30 mm Hg decompression of the eye for 15 minutes before the injection showed a mean IOP of only 20.6 mm Hg after the injection. Mercury bag decompression of the eye significantly reduced the rise in IOP following intravitreal injection (difference in the mean IOP rise = 26.4 mm Hg, df = 54, t = 7.67, p < 0.001). Without ocular decompression before injection, all patients complained of temporary loss of vision, and reflux of the injection solution was frequently observed. Use of ocular decompression also reduced the discomfort of the injection. Throughout the full course of treatment by this means there were no adverse effects on the visual acuity. This technique is recommended to those performing intravitreal injections. PMID- 8218056 TI - Ultrastructure of retinal vessels in diabetic patients. AB - The ultrastructure of retinal vessels was examined in three eyes from diabetic patients and two eyes from control subjects. In some of the retinal blood vessels of each of the diabetic eyes, the endothelial cytoplasm was thin and had fenestrae. These fenestrations which were seen in both capillaries and venules, were closed by a thin diaphragm. Transendothelial channels were also observed in the endothelial cytoplasm. The tight junctions between endothelial cells were rarely altered. The junctions were open with short adherent regions in which the junctional membranes showed increased electron density. These morphological changes may account for the characteristic breakdown of the blood-retinal barrier in diabetic patients. PMID- 8218057 TI - Cataract and myotonic dystrophy: the role of molecular diagnosis. AB - Myotonic dystrophy (dystrophia myotonica), the commonest and most variable of the muscular dystrophies of adult life, has long been known to be associated with cataract, while slit-lamp examination for specific lens opacities has been one of the principal methods of presymptomatic detection of gene carriers. The recent discovery that the myotonic dystrophy mutation is an unstable DNA sequence, composed of varying numbers of CTG triplet repeats, now allows a specific molecular test for this disorder, as well as explaining the phenomenon of anticipation. A series of case reports is presented to illustrate the important practical applications of this development in relation to ophthalmic aspects of the disorder. Reassessment of the specificity of the ophthalmic changes may be required and it will be important for molecular analysis to be used alongside ophthalmic studies, when determining whether family members carry the mutation for myotonic dystrophy. PMID- 8218058 TI - Cellular autoimmunity to retinal specific antigens in patients with Behcet's disease. AB - The notion that autoimmune mechanisms play a role in the pathogenesis of certain uveitic conditions in humans is supported by the observation that lymphocytes from such patients respond in culture against retinal specific antigens which are uveitogenic in animals. A large proportion of uveitis patients with Behcet's disease are reported to respond well to S antigen, to interphotoreceptor retinoid binding protein (IRBP) and to several of their uveitogenic peptides, in particular, the S antigen derived peptide M. Patients with Behcet's disease without ocular involvement were reported not to differ in their responses to S antigen from the responses in the control group, yet 35% of them responded to IRBP and approximately two thirds of them responded to the peptides (peptide M, peptide N, R-4, or R-14). The responses were inhibited by monoclonal antibodies to CD4 and to class II MHC HLA-DR molecules. The presence of lymphocyte responses to retinal antigens in patients with Behcet's disease without uveitis might indicate a preclinical stage of ocular involvement. Thus, these data support the idea that autoimmunity to retinal specific antigens may play a role in the ocular inflammation in Behcet's disease. PMID- 8218059 TI - Adverse effects of topical antiglaucomatous medications on the conjunctiva. PMID- 8218060 TI - Ocular melanomas in xeroderma pigmentosum. PMID- 8218061 TI - Intracavernous chondrosarcoma associated with Ollier's disease. PMID- 8218062 TI - A rare cause of visual loss in AIDS patients: central retinal vein occlusion. PMID- 8218063 TI - Persistent visual changes following hashish consumption. PMID- 8218064 TI - Dirofilariasis: an uncommon parasitosis of the eye. PMID- 8218065 TI - Retrobulbar oedema after ophthalmic plaque radiotherapy. PMID- 8218066 TI - Retinal arterial macroaneurysm in a patient with congenital heart disease. PMID- 8218067 TI - Visual loss from central serous retinopathy in systemic lupus erythematosus. PMID- 8218068 TI - Differential diagnosis of iridocorneal endothelial syndrome and posterior polymorphous endothelial dystrophy. PMID- 8218069 TI - Recent evaluation of prognostic risk factors in esophageal atresia--a multicenter review of 223 cases. AB - In this study, 223 cases of esophageal atresia (Type IIIb: 85.7%; Type II: 5.8%; Type IIIc: 4.0%; Type IIIa: 2.2%; Type IV: 2.2%) from 6 pediatric surgery centers of Austria, were retrospectively examined for the following parameters and their influence on the prognosis: Birth weight (2494.7 +/- 702.0 g), gestation week (range 27-42 weeks; mean 37.3 +/- 3.1 weeks), sex (male: n = 128; female: n = 95), long-gap atresia (> or = 2 cm: n = 33), Tracheomalacia (n = 16), associated malformations (n = 122; cardiac 27.4%, renal 17.9%, skeletal 17.0%, anal: 10.3%, intestinal 9.9%, mediastinal 7.6%, chromosomal 2.2%), preoperative aspiration (n = 92), pneumonia (n = 96), anastomotic insufficiency (n = 45), empyema (n = 5), mediastinitis (n = 8), sepsis (n = 32), other medical complications (n = 122, in 80 infants), other surgical complications (n = 57). The mortality rate was 41.3% overall, from 1975 to 1991; however, it was 25% from 1987 to 1991 and 0% in 1991. A statistically significant correlation was found between prognosis and the following factors: Cardiac malformations (p = 0.0001), medical complications except aspiration and pneumonia (p = 0.0001), empyema (p = 0.0081), mediastinitis (p = 0.0214), and sepsis (p = 0.0295). These 5 significant factors were given different points and a prognostic score was calculated by the addition of these points. This score was predictive for survival in 90.6% of cases and for mortality in 94% of cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218071 TI - Intrahepatic biliary lesions following blunt liver trauma in children--is nonoperative management or conservative operative treatment always safe? AB - Nonoperative management of blunt liver injuries has become standard care for children, in the absence of hemodynamic instability. However, attention has to be drawn to biliary complications which can manifest themselves after a latent period, even in the presence of rupture of main biliary ducts. Peripheral bile duct lesions are easily treated by wide drainage. However, the extremely rare intrahepatic main bile duct lesions require other treatments. We report 2 cases of severe liver trauma associated with intrahepatic bile duct lesions: the first, managed nonoperatively, developed biliary peritonitis on day 21. Lesions of the main right biliary ducts were discovered. Because the right liver vascularization was not compromised, an intrahepatic biliary reconstruction was performed through a large hepatotomy according to the functional anatomy. The second child, who had an emergency laparotomy on admission, suffered nevertheless from a bilioma, drained on day 38. Because of increasing daily bile flow through the drain a second laparotomy was performed that demonstrated a biliary leak from a main segmental duct. Resection of the segment cured the patient. These two cases illustrate the occurrence of intrahepatic main bile duct lesions, clinically apparent after a latent period, following blunt trauma of the liver treated by nonsurgical or conservative surgical management. Intrahepatic biliary reconstruction is an alternative to liver resection when viable vascularization of the involved sector justifies its preservation. PMID- 8218070 TI - Postoperative vomiting in children. A persisting unsolved problem. AB - Nausea and vomiting after anaesthesia and surgery in children remains a major problem. The following survey studies the frequency of postoperative vomiting and relates it to the anaesthetic technique, the surgical procedure, and postoperative analgesia. During one year, September 1989 until September 1990, 2370 surgical patients requiring anaesthesia were studied prospectively with the following protocol: 1) patient data, surgery and anaesthesia technique; and 2) postoperative follow-up were registered. Outpatients were followed up by telephone. The overall incidence of vomiting was 19.5%, which was lower than in other studies. An increased incidence of vomiting was found in children over 2 years of age, after certain operative procedures, and after general anaesthesia. Furthermore, postoperative opioid administration on the ward increased the risk of vomiting. Despite the low overall incidence of vomiting in our study, we still found a high frequency after certain surgical procedures. The use of regional anaesthesia, prophylactic antiemetic medication, and the introduction of new anaesthetics, may help to reduce the sometimes high incidence of postoperative nausea and vomiting in paediatric patients. PMID- 8218072 TI - Biliary atresia--bile acids and prostaglandin E2 in cell cultures of bile duct epithelia. AB - In a cell culture model of bile duct epithelial cells, the effect of prostaglandin E2, lithocholic acid and deoxycholic acid was studied. Bile acids and prostaglandin are administered postoperatively in biliary atresia empirically as choleretics. Prostaglandin E2 and the bile acids all had inhibitory effects on bile duct epithelial cells in culture. There is no clinical study proving the efficacy of either bile acids or prostaglandin E2 in biliary atresia. The negative results with these substances in cell cultures warrants reserve in their routine clinical use in biliary atresia. PMID- 8218073 TI - The use of the laser in the treatment of arterio-venous malformations and vascular tumours of the liver. AB - Vascular tumours of the liver present variously in the paediatric age group. Their clinical course depends on tumour size, its growth characteristics, localization and complications. The most feared complications are cardiac failure and the Kasabach-Merritt syndrome which may occur in up to 50% of affected children. In haemangioendotheliomata and capillary haemangiomata spontaneous regression can be expected. Regression may be stimulated by x-ray radiation therapy, corticosteroids, Endoxane or alpha Interferon. Emergency percutaneous catheter embolization or operation must be carried out in the event of such complications. The Nd:YAG laser is particularly well suited for these cases. In all events, careful interdisciplinary cooperation among paediatricians, radiologists, cardiologists, oncologists and paediatric surgeons is required owing to threatening complications which mostly occur in neonates and infants. PMID- 8218074 TI - Is neuronal intestinal dysplasia (NID) a primary disease or a secondary phenomenon? AB - In order to identify possible underlying ganglion-cell disorders, specimens have been taken in neonates and infants with intestinal obstruction treated between January 1988 and June 1992. NID was confirmed in 3 patients with intestinal malformation, 2 patients with neonatal intestinal obstruction, 3 patients with meconium peritonitis, 1 patient with persistent constipation after Duhamel's pull through for Hirschsprung's disease and 1 patient with rectal stricture after conservative treatment for necrotising enterocolitis. Additionally, NID was found in 1 patient with recurrent prolapse of an ileostomy. Associated Hirschsprung's disease has been ruled out by additional rectal suction biopsies in patients where specimens have been collected at laparotomy first. Development of NID in previous normal bowel, the association of NID with intestinal malformations as well as the clinical heterogeneity of patients with NID of the present series suggest that NID is a reaction of the neural intestinal system caused by congenital obstructive factors or inflammatory diseases. PMID- 8218075 TI - First experience with a distraction apparatus prototype (SM-fix-phalanx distractor) for phalanges lengthening. AB - Since 1991 seven children aged between 5-17 years have been treated at the University Children's Hospital in Basel for 10 traumatically partially amputated phalanges with a newly developed external fixator and distractor. Through continual distraction of the osteotomy a phalanx lengthening of 3-10 mm has been achieved (on average 55% of the rest phalanx). The results of this method in distal phalanx amputation with resulting nail dystrophy (claw nail) has shown functional and cosmetic improvements. The average distraction and consolidation phases lasted 5 weeks. The after care lasted 2-12 months. As children have good distraction-histogenesis bone grafting is not necessary. A prerequisite would be, however, an intact or appropriately prepared integument. The advantage of this external fixator and distractor system is that it is suitable for the delicate anatomical structures of a child's hand. The distractor component is only necessary for a distraction step to be carried out. A further advantage of this system is the relatively light but stable construction. PMID- 8218076 TI - Cranioplasties for congenital and acquired skull defects in children--comparison of new concepts with conventional methods. AB - From 1974 to 1992 fifty-two patients with congenital or acquired skull defects were operated at the Department of Pediatric Surgery of the University Children's Hospital of Zurich. By 1988, in 26 patients conventional methods with PMMA (polymethyl methacrylate) plasties or rib plasties were performed. After 1988, in 26 patients skull reconstruction was done by skull splitting, application of lyophilized bone or cartilage or a combination of both. In the latter period, stabilization and fixation was always provided by biodegradable screws and bands. The results of the different techniques were compared in a retrospective fashion. PMMA plasties provided immediately full stability and good cosmetic results. Another advantage was their availability. In one patient (= 4.8%), a wound infection required the removal of the plasty. In two other patients (9.5%), an increasing mobility of the plasty could be observed during skull growth. Rib plasties were not satisfying. Skull splitting or reconstruction with lyophilized bone or cartilage showed good results with a stable integration within 3-4 months. In one patient (4%), a superficial wound infection occurred, but it did not affect the plasty. From the present study, we conclude that skull splitting or the reconstruction of skull continuity by means of lyophilized bone or cartilage with fixation through biodegradable screws and bands are the methods of first choice in children, because they are fully integrated, avoid foreign material and might have a slightly lower risk of infection. In addition, removal of the implants may be avoided.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218077 TI - Laryngo-tracheo-oesophageal cleft: a plea for early diagnosis. AB - Congenital laryngeal clefts are rare. This paper reports on the management of 3 patients with Type 2 laryngo-tracheo-oesophageal cleft. One patient died following tracheopexy after successful cleft closure. Prognosis is related to the presence of other major anomalies, the early diagnosis of the lesion and institution of appropriate respiratory and nutritional care prior to correction of the defect. A greater awareness of the condition combined with aggressive diagnostic endoscopy should result in early diagnosis and improved survival. PMID- 8218078 TI - Annular pancreas associated with pancreaticobiliary maljunction in an infant. AB - We report the first known case of an annular pancreas associated with pancreaticobiliary maljunction without cholangiectasis in an infant, aged 2 years and 5 months in Japan. Only two other cases have been reported in Japan both of which were in adults. In our case, the main clinical features were abdominal pain, vomiting and an increasing level of plasma amylase. Endoscopic retrograde cholangiopancreatography (ERCP) was not successful in demonstrating the pancreaticobiliary maljunction due to duodenal stenosis. At operation, a complete type of annular pancreas was found with no enlargement of the common bile duct. We could visualize the pancreaticobiliary maljunction using cholangiopancreatography from the gallbladder during the operation. We then performed duodeno-duodenostomy (side-to-side anastomosis, diamond anastomosis) and portal jejunostomy (Roux en Y anastomosis). The infant was discharged in a good condition at 13 days after the operation. The pattern of the pancreatic ducts was Millbourn's 2a and the type of the duct in the annular portion was Yumura's type I. These results correspond to Lecco's hypothesis that the ring formation originates from the ventral pancreas. It has been further suggested that the cacogenesis and/or dysplasia of the ventral pancreas plays a role in the development at the stage of the pancreaticobiliary maljunction. PMID- 8218079 TI - Ureteric cyst: an unusual abdominal mass. AB - Abdominal cystic masses in childhood are rare and despite improved imaging techniques continue to present diagnostic confusion. Typically such cystic lesions are mesenteric or intestinal in origin. However, rarer causes include cystic dilatation of a blind ending ureter. To date over 100 cases of blind ending ureters have been reported and their management described. We report on a case of non-communicating ureteric cyst associated with a blind ending ureter that recurred following percutaneous drainage and required operative resection. Although percutaneous drainage techniques have been advocated for a variety of abdominal cystic lesions, the experience gained from this case suggests that operative excision is the treatment of choice. PMID- 8218080 TI - Facial nerve reconstruction following ablative parotid surgery. AB - Sacrifice of the facial nerve during surgery for parotid malignancy is rarely necessary, but the sequelae of facial nerve paralysis necessitates some form of facial re-animation. The technique which achieves the best results is that of immediate nerve grafting. This paper records our experience with 14 cases of extra temporal reconstruction of the facial nerve, utilizing the cutaneous branch of the radial nerve as an autograft. PMID- 8218081 TI - Functional primary closure of cleft lip. AB - A technique of primary closure of the cleft lip is described. It is based on a complete understanding of the anatomy of the entire facial musculature such that it can be restored to normality and so encourage normal function and development. PMID- 8218082 TI - Post-operative infection of Proplast facial implants. AB - Proplast is an ultra-porous composite material that has been used widely to augment the facial skeleton. In recent years, however, the popularity of this material has declined because of complications associated with its use. This paper presents a retrospective study of 36 cases treated with 88 Proplast implants at one unit over a nine-year period. The results suggest that infection of the implant is the most common post-operative complication. Infection may occur at any time following implantation and appears to be more likely when implantation is associated with an osteotomy procedure. In addition, the overall rate of infection in this study (16%) was higher than reported previously and the male-female ratio was 2:1. The possible factors involved in infection are discussed. PMID- 8218083 TI - Desmoplastic variant of ameloblastoma in Malaysians. AB - Seventeen cases are reported of desmoplastic variant of ameloblastoma of the jaws observed during the years 1967-1991. There were 12 females and 5 males, and these consisted of 7 Chinese, 6 Malays, 2 Indians, 1 Sikh and 1 Kadazan. Their ages at diagnosis ranged from 21-60 years with a mean of 36.6 years. There were 10 mandibular and 7 maxillary tumours. Of these, 14 cases involved the anterior segment with extension to the premolar region in 5 cases. 60% of cases were radiologically suggestive of fibro-osseous lesions. The main mode of treatment was resection and 1 case presented with recurrence. The findings of this study were compared with those of previous reports. PMID- 8218084 TI - The management of patients with carcinoma of the tongue. AB - Surgery, radiotherapy or the combination of these two modalities remains the accepted treatment for squamous carcinoma of the tongue. In the 10-year period between 1982 and 1992, 121 patients presented to the combined Maxillofacial/Radiation Oncology Clinic, Royal Infirmary, Edinburgh with carcinoma of the tongue. The majority of T1 tumours have been treated by surgical excision, almost equal numbers of T2 tumours were treated by surgery or radiotherapy, T3 and T4 tumours without evidence of nodal disease were treated by radiotherapy. Patients presenting with established nodal disease or involvement of bone were treated primarily by surgery. The patients presenting with T3 and T4 tumours were combined to produce a more realistic figure for statistical analysis. The actual 5-year survival rates for patients presenting from 1982 to 1987 for T1, T2 and T3/4 tumours are 83%, 63% and 0% respectively. Five year actuarial survival rates for patients from 1987 to 1992 are 89%, 69% and 47%. In the absence of nodal disease in the retrospective group, T1, T2 and T3/4 carcinomas of the tongue have actual 5-year survival rates of 93%, 87% and 0% respectively. Patients who present with or later develop nodal disease have a poorer prognosis with survival rates of 33%, 33% and 0% for T1, T2 and T3/4 tumours. The size of the primary tumour did not significantly affect the five year survival rate when nodal disease was present. PMID- 8218085 TI - Versatile mucoperiosteal retractors for cleft palate surgery. PMID- 8218086 TI - An infarcted Warthin's tumour presenting with facial weakness. AB - It is rare for benign salivary gland neoplasms to cause facial nerve weakness. We present such a case occurring in a 70-year-old patient with an infarcted Warthin's tumour and review the benign causes of facial nerve impairment. PMID- 8218087 TI - Malignant melanoma of the parotid gland: a case report and literature review. AB - A case is reported of a malignant melanoma presenting in a parotid gland with no other primary lesion detectable. The pathological feasibility of primary malignant melanoma of the parotid is discussed together with a review of the literature. PMID- 8218088 TI - Oral metastasis in malignant pleural mesothelioma. AB - A case is reported of a 48-year-old man with malignant sarcomatous pleural mesothelioma, who presented with a secondary deposit in the mandibular alveolus. We believe that this is the first reported case of this nature. PMID- 8218089 TI - Anterior lingual mandibular salivary gland defect--a dilemma in diagnosis. AB - Anterior lingual mandibular salivary gland defects are very rare. These lesions present as non-definitive bony radiolucencies. There are several other radiolucent entities which present in the anterior mandible with greater frequency and this creates a diagnostic dilemma for the practitioner. The ultimate and proper treatment of non-treatment depends on a correct diagnosis of these lesions. The correctness of the diagnosis and avoidance of unnecessary traumatic procedures may be aided by more sophisticated radiographic studies, such as a CAT scan and/or Magnetic Resonance Imaging. A case of a very unusual appearing anterior lingual mandibular salivary gland defect is presented and the diagnosis, management and recommendation for more complex radiographic studies are discussed. PMID- 8218090 TI - Acute enlargement of the tongue. AB - Acute enlargement of the tongue can present as an emergency. The problems of management in the acute situation and the diagnosis of the underlying condition are discussed and illustrated with reference to four unusual cases. There is a case for a simple classification and such a classification is presented. PMID- 8218091 TI - Making drain shortening an easy task. PMID- 8218092 TI - Presentation of the DePuy Award to Mr Brian Avery. PMID- 8218093 TI - TMJ dysfunction--the surgical dilemma. PMID- 8218094 TI - Studies of factor Xa/phospholipid-induced intravascular coagulation in rabbits. Effects of immunodepletion of tissue factor pathway inhibitor. AB - In earlier studies from this laboratory evidence was obtained for a physiological function of tissue factor pathway inhibitor (TFPI) as a regulator of hemostasis capable of preventing thrombotic complications that might otherwise result from exposure of blood to trace amounts of tissue factor (TF). However, it was not possible to conclude that the protective effect of TFPI stemmed solely from inhibition of factor VIIa/TF catalytic activity, since TFPI neutralizes stoichiometric amounts of factor Xa in forming an inhibited factor Xa/TFPI/factor VIIa/TF complex. Therefore, we examined the effects of immunodepletion of TFPI on the extent of coagulation initiated in rabbits by exposure to factor Xa and phospholipid in the absence of TF. In one experimental approach, factor Xa was generated endogenously with the factor X-activating fraction of Russell's viper venom (0.33 microgram/kg) in rabbits receiving an infusion of phosphatidylcholine/phosphatidylserine (PCPS) vesicles, 1 mg/kg over 2 hours. In a second approach, rabbits were injected with a complex of factor Xa (0.75 microgram/kg) and PCPS (12.5 micrograms/kg). In contrast with the observed sensitization of TFPI-depleted rabbits to TF-induced coagulation, TFPI-depleted rabbits were not sensitized to coagulation initiated by factor Xa and phospholipid in the absence of TF. These data support the conclusion that the physiological function of TFPI in regulating TF-dependent coagulation stems primarily from its ability to inhibit factor VIIa/TF catalytic activity. PMID- 8218095 TI - The relation of lipoprotein[a] concentrations and apolipoprotein[a] phenotypes with asymptomatic atherosclerosis in subjects of the Atherosclerosis Risk in Communities (ARIC) Study. AB - Plasma levels of lipoprotein[a] (Lp[a]) are associated with increased risk of coronary artery disease and show an inverse correlation with apolipoprotein[a] (apo[a]) molecular weight. We determined Lp[a] levels and apo[a] phenotypes in 171 cases with preclinical extracranial carotid atherosclerosis as ascertained by B-mode ultrasound and in 274 control subjects free of carotid atherosclerosis. Lp[a] protein levels measured by enzyme-linked immunosorbent assay ranged from 4 to 361 micrograms/mL in cases and from 2 to 392 micrograms/mL in controls, but median levels of Lp[a] were higher in cases than in controls (51 micrograms/mL versus 33 micrograms/mL, P < .003). In both groups, all 11 apo[a] polymorphs that are resolved by the procedure used were present, resulting in 43 and 39 different apo[a] phenotypes in cases and controls, respectively. An inverse relation between apo[a] polymorph size and Lp[a] level was observed in both cases (r = 0.49, P < .001) and controls (r = -0.34, P < .001). Apo[a] phenotype distributions were similar in cases and controls. However, in 17 phenotypes with three or more subjects per group, the difference of mean Lp[a] concentrations between cases and controls was 32 +/- 36 micrograms/mL (mean +/- SD). Thus, the higher Lp[a] levels in cases were not associated with a greater prevalence of small apo[a] polymorphs. Stepwise logistic regression analyses of known risk factors for coronary heart disease showed that plasma Lp[a] concentration was an independent predictor of case-control status, while Lp[a] phenotype was not, irrespective of the presence or absence of Lp[a] concentration in the model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218096 TI - Phospholipase C activity in platelets from Bernard-Soulier syndrome patients. AB - The levels of glycoprotein (GP) Ib and GPV and phospholipase C activity were measured in platelets from three Bernard-Soulier syndrome patients. The patients' platelets had 46%, 46%, and 24% of control levels of GPIb alpha and 43%, trace, and 13% of control levels of GPV as determined by immunoblot analysis. Stimulation by thrombin, trypsin, the thromboxane analogue U46619, and the combination of U46619 and trypsin caused the formation of [32P]phosphatidic acid, an index of phospholipase C activity, in [32P]orthophosphate-prelabeled platelets. With all agonists, however, the formation of [32P]phosphatidic acid was markedly reduced in Bernard-Soulier syndrome platelets compared with control platelets. These data indicated a postreceptor defect in phospholipase C activation in Bernard-Soulier syndrome platelets and confirmed earlier observations of potential proteolytic and nonproteolytic mechanisms of platelet activation. PMID- 8218097 TI - Aortic smooth muscle cells in a three-dimensional collagen lattice culture. Evidence for posttranslational regulation of collagen synthesis. AB - Aortic smooth muscle cells were cultivated as monolayers on plastic or within collagen lattices with low- and high-serum supplementation, and the expression of mRNAs specific for pro alpha 1 (I) and pro alpha 1 (III) collagen were studied by slot blot hybridization. The steady-state levels of pro alpha 1 (I) and pro alpha 1 (III) collagen mRNA of cells within collagen lattices were found to be higher than those grown on plastic, although the production of collagen was lower. The degradation of pro alpha 1 (I) and pro alpha 1 (III) collagen mRNAs as revealed in the presence of actinomycin D was not affected by culturing the cells within a collagen lattice. In vitro translation assays of mRNAs of monolayer- and lattice cultured cells showed no differences in translatability. These data suggest the involvement of posttranslational control of collagen production in collagen lattice-cultured smooth muscle cells. PMID- 8218098 TI - Effect of 3-thiadicarboxylic acid on lipid metabolism in experimental nephrosis. AB - The effect of the sulfur-substituted fatty acid analogue 1,10 bis(carboxymethylthio)decane, also known as 3-thiadicarboxylic acid, on puromycin aminonucleoside-induced nephrotic hyperlipidemia was studied in rats. Treatment with 3-thiadicarboxylic acid (250 mg/kg) for 5 days reduced plasma levels of triglycerides from 5.8 to 2.7 mmol/L and cholesterol from 11.0 to 7.7 mmol/L. This was accounted for by decreases in very-low-density lipoprotein triglycerides, very-low-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, without any major changes in the composition of plasma lipoproteins. The activities of two enzymes involved in fatty acid synthesis (ATP:citrate lyase and fatty acid synthetase) were inhibited by 3 thiadicarboxylic acid treatment, whereas acetyl-coenzyme A carboxylase activity was unchanged. In contrast, treatment with the sulfur-substituted fatty acid analogue induced the peroxisomal beta-oxidation of fatty acids ninefold and the mitochondrial beta-oxidation by 54% to 73%, depending on the substrate used. This was accompanied by a 26% reduction in hepatic triglyceride secretion rate. The hepatic phosphatidate phosphohydrolase activity was unchanged. 3-Thiadicarboxylic acid treatment suppressed the activity of the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, by 58%, whereas hepatic LDL receptor expression was unaltered. The activities of lipoprotein lipase and hepatic lipase were unchanged by treatment. These results demonstrated that treatment with 3-thiadicarboxylic acid ameliorates hyperlipidemia in experimental nephrosis primarily by decreasing the overproduction of very-low density lipoprotein present. The data also indicate that hepatic very-low-density lipoprotein synthesis and secretion is strongly influenced by the availability of the fatty acid substrate under the same hyperlipidemic conditions. PMID- 8218099 TI - A cross-sectional study of endogenous tissue plasminogen activator, total cholesterol, HDL cholesterol, and apolipoproteins A-I, A-II, and B-100. AB - Elevated levels of endogenous tissue-type plasminogen activator (t-PA) appear to be a marker for preclinical atherosclerosis. At present, however, data describing potential relations between plasma t-PA level and established lipid risk factors for coronary atherosclerosis are sparse. To explore these potential relations, we measured plasma levels of t-PA antigen (t-PA:ag) in 633 apparently healthy men in the Physicians' Health Study as well as total cholesterol, high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol, HDL3 cholesterol, and apolipoproteins A-I, A-II, and B-100. Overall, plasma t-PA:ag levels were inversely correlated with HDL cholesterol (r = -.1616, P < .0005), HDL2 cholesterol (r = -.1632, P < .0005), and HDL3 cholesterol (r = -.0927, P = .019). In stratified analyses, the inverse association between t-PA:ag and HDL cholesterol was present among frequent (P trend = .002) and infrequent (P trend = .004) consumers of alcohol as well as among the subgroups of frequent exercisers (P trend < .001), men in the lower half of body mass index (P trend = .001), and nonsmokers (P trend < .001). In contrast, there was no association between t PA:ag and total cholesterol (r = .0219, P = .58), whereas relations of t-PA:ag with apolipoproteins A-I, A-II, and B-100 were minimal and of borderline significance. These data indicate that plasma levels of endogenous t-PA:ag are inversely related to HDL cholesterol as well as HDL2 and HDL3 cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218100 TI - Recombinant leech antiplatelet protein prevents collagen-mediated platelet aggregation but not collagen graft thrombosis in baboons. AB - Leech antiplatelet protein (LAPP) is a specific inhibitor of collagen-induced human platelet aggregation and adhesion to collagen under static conditions. Recombinant LAPP (rLAPP) and L-366,763 (acetylated-Cys-Asn-Pro-Arg-Gly-Asp-Cys NH2), a peptidyl fibrinogen receptor antagonist, were evaluated in an anesthetized baboon thrombosis model using a collagen-coated graft segment of an arteriovenous shunt to elicit thrombus formation. Animals were randomized to receive systemic intravenous administration of rLAPP (100 micrograms.kg-1 x min 1; n = 5), L-366,763 (8.5 micrograms.kg-1 x min-1; n = 3), or saline (n = 3). Despite complete and selective inhibition of type I collagen-induced ex vivo aggregation of platelets, rLAPP had no significant effect on the rate or the extent of 111-In-labeled platelet deposition onto the collagen graft and no effect on template bleeding time. In contrast, L-366,763 completely prevented platelet deposition, maintained blood flow, and significantly prolonged bleeding time at the dosage that inhibited ex vivo aggregation in response to all agonists studied. In this study, the absence of an antithrombotic benefit of rLAPP contrasted sharply with the efficacy of the fibrinogen receptor antagonist. These results demonstrate that specific inhibition of collagen-mediated platelet aggregation alone is not sufficient to prevent platelet-dependent thrombosis in this baboon model. PMID- 8218101 TI - The assembly of the prothrombinase complex on adherent platelets. AB - Prothrombinase complex assembly, in real time, on platelets adherent to immobilized von Willebrand Factor (vWf) was examined by total internal reflection fluorescence spectroscopy (TIRFS). Electron microscopy showed that the platelets adhered to vWf in a largely unactivated state and could be activated by thrombin. Antibody binding to glycoprotein (GP) Ib and functional GPIIb-IIIa receptor molecules on adherent platelet membranes monitored by TIRFS also indicated that platelets adhered in a largely unactivated state. Maximal expression of the receptor form of GPIIb-IIIa detected by antibody binding was seen only after thrombin stimulation of the adherent platelets. Antibody binding to GPIb was detected on adherent platelets. A reduction in antibody binding was observed after thrombin stimulation of the platelets, indicating a change in GPIb as a consequence of thrombin stimulation of the platelets. The binding of the protein components of the prothrombinase complex to adherent and thrombin-stimulated adherent platelets was then studied individually. Factor Va bound to adherent and thrombin-stimulated adherent platelets was then studied individually. Factor Va bound to adherent and thrombin-stimulated adherent platelets with an estimated Kd of 58 nmol/L. Minimal factor Xa binding was observed on adherent platelets before thrombin stimulation. Factor Xa binding was, however, readily observed on thrombin-stimulated adherent platelets. This factor Xa binding was not saturable, and no Kd value could be estimated. Direct measurement of prothrombinase complex assembly was demonstrated by using an energy transfer phenomenon between fluorescein-labeled factor Va and rhodamine-labeled factor Xa. Prothrombinase complex assembly was observed on both adherent and thrombin-stimulated adherent platelets. The estimated Kd for the factor Va/factor Xa interaction was 4 nmol/L. TIRFS demonstrated that adherent platelets have the ability to support prothrombinase complex assembly, as shown by a direct energy transfer reaction between fluorescently labeled factors Va and Xa. PMID- 8218102 TI - Intact platelet membranes, not platelet-released microvesicles, support the procoagulant activity of adherent platelets. AB - The possibility that platelets release microvesicles on adherence to either von Willebrand factor (vWf) or collagen was examined by flow cytometry analysis of the supernatant above layers of adherent platelets. No microvesicle release was detected as a result of adherence to vWf or to collagen, a known platelet agonist. Approximately 8% of the total platelet mass was released as microvesicles after thrombin stimulation of the vWf- or collagen-adherent platelets. A larger portion of the vWf-adherent platelet membranes (approximately 21%) was released as microvesicles subsequent to platelet stimulation with the nonphysiological agonist calcium ionophore A23187. Calpeptin, a calpain inhibitor, had no effect on microvesicle release, suggesting that calpain proteolysis of platelet cytoskeletal proteins was not responsible for microvesicle shedding under the conditions studied. Examination of the vWf adherent platelets by scanning electron microscopy showed that virtually no microvesicles bound to exposed vWf multimers. No microvesicle binding to the adherent platelets was observed, indicating that the majority of the microvesicles were shed from the platelet and vWf surface on platelet activation. The ability of the microvesicle population to support procoagulant activity was measured with a prothrombinase activity assay and was compared with the activity supported by the adherent platelet membranes. More than 85% of the total prothrombinase activity remained associated with the adherent platelet membranes, both for unstimulated platelets and platelets stimulated with physiological agonists. Furthermore, the residual activity found in the buffer fraction containing detached platelets and any released microvesicles could be attributed to the detached platelets. No activity could be attributed to the microvesicles, as thrombin stimulation of either vWf-or collagen-adherent platelets did not promote increased procoagulant activity relative to the unstimulated adherent platelets, even though microvesicle release was detected as a result of agonist addition. Neither full platelet activation nor microvesicle shedding played an essential role in generating procoagulant activity in the adherent platelet system. PMID- 8218103 TI - LDL size and subclass pattern in a biethnic population. AB - Recently, the presence of small, dense low-density lipoprotein (LDL) has been recognized as a risk factor for coronary heart disease. There has been little work on correlates of LDL size in population-based studies and none in Mexican Americans. We examined the relationship of LDL size and pattern to anthropometric and metabolic variables in 466 Mexican Americans and non-Hispanic whites in the San Antonio Heart Study. LDL size in Angstrom units was significantly lower in Mexican Americans (255.8 +/- 0.6) than in non-Hispanic whites (257.9 +/- 0.7) (P = 0.041) after adjustment for gender and age. The percentage of subjects with pattern B tended to be higher in Mexican Americans than in non-Hispanic whites (40.0% versus 34.4%, respectively), although this difference did not reach statistical significance. In univariate analysis, LDL size was significantly associated with glucose (r = -.20), insulin (r = -.19), male gender (r = -.20), total cholesterol (r = -.22), high-density lipoprotein cholesterol (HDL-C) (r = .53), and triglyceride concentrations (r = -.63). In multivariate analyses, higher triglyceride, insulin, and glucose concentrations, lower HDL-C, and male gender were independent correlates of smaller, denser LDL. Correlates of LDL size were similar in Mexican Americans and non-Hispanic whites. Our results confirm previous reports that triglyceride and HDL-C concentrations are the most important variables associated with LDL size. The additional findings of independent effects of male gender, glucose, and insulin concentrations suggest that sex hormones and the insulin resistance syndrome may also play an important role.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218104 TI - Parental history of early myocardial infarction is associated with decreased levels of lipoparticle AI in adolescents. AB - A family history of coronary heart disease (CHD) is a known risk factor for CHD. To investigate the possible role of lipoprotein particles in the relationship between family history of CHD and risk of CHD, we performed a case-control study in a sample of adolescents. The case group consisted of 97 adolescents whose parents had suffered a verified myocardial infarction before the age of 55 years. The control group was composed of 194 subjects without any family history of CHD. One case patient was matched to two control subjects for gender, age, and body mass index. In both groups, plasma lipid variables were measured, including total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) low density lipoprotein cholesterol, apolipoprotein (apo)AI, apoB, apoAI-containing lipoprotein particles without apoAII (LpAI) and with apoAII, and apoB-containing lipoprotein particles with apoE and with apoCIII. Adolescents with a family history of early myocardial infarction had lower plasma levels of HDL-C (P < .0001), apoAI (P < .01), and LpAI (P < .0001) than control subjects (adjusted for gender, age, body mass index, smoking habits, and oral contraceptive use). No other differences were statistically significant between case and control subjects. The analysis was repeated separately for male and female subjects. In young men, the best predictor of family history of early myocardial infarction was the LpAI plasma level, whereas in young women it was the HDL-C plasma level. Decreased levels of HDL-C and LpAI lipoprotein particles explain part of the relationship between parental history of early myocardial infarction and CHD risk. PMID- 8218105 TI - Oral contraceptives decrease hepatic cholesterol independent of the LDL receptor in nonhuman primates. AB - Pharmacological doses of estrogens have been reported to increase hepatic catabolism of low-density lipoprotein (LDL) by the LDL receptor (LDL-R) pathway and to increase the concentration of mRNA for the LDL receptor. The induction of LDL-Rs by large doses of estrogen may not be relevant to the role of estrogens under physiological conditions. Furthermore, the mechanisms by which oral contraceptives, a combination of synthetic estrogen and progestin, may modulate LDL metabolism remain largely unexplored. Adult female cynomolgus monkeys were given combination ethinyl estradiol/norgestrel preparations (n = 16) for 16 weeks and were compared with a control group that did not receive exogenous sex hormones (n = 7). All animals consumed a diet containing 0.25 mg cholesterol/kcal with 40% of calories from saturated fats. After 16 weeks of treatment there was no significant difference in LDL cholesterol (LDL-C) and hepatic LDL-R mRNA concentration between oral contraceptive-treated animals (LDL-C, 242 +/- 113 mg/dL; LDL-R mRNA, 0.60 +/- 0.31 pg/microgram RNA) and control animals (LDL-C, 277 +/- 100 mg/dL; LDL-R mRNA, 0.51 +/- 0.21 pg/microgram RNA). In contrast, the hepatic cholesteryl ester concentration was significantly lower in the oral contraceptive-treated animals (7.28 +/- 3.59 mg/g liver) compared with the control animals (16.07 +/- 11.86 mg/g liver; P = .01) with no significant difference in hepatic free cholesterol concentration between the groups. Thus, oral contraceptives decrease hepatic cholesterol concentration independent of LDL R expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218106 TI - Human type II hyperlipoproteinemia enhances platelet-collagen adhesion in flowing nonanticoagulated blood. AB - We investigated the effects of high plasma lipid levels on platelet adhesion and platelet thrombus formation in nonanticoagulated human blood on collagen fibrils at an arterial wall shear rate of 2600 seconds-1. Nonanticoagulated blood was drawn directly at a flow rate of 10 mL/min for 3 minutes from an antecubital vein of patients with type IIa (n = 5) and type IIb (n = 4) hyperlipoproteinemia over purified human type III collagen fibrils that were positioned on a plastic coverslip in a parallel-plate perfusion chamber. Results were compared with those obtained in healthy individuals with normal lipid plasma levels (n = 9). Blood collagen interactions were quantified by morphometry as platelet-collagen adhesion, thrombus volume, and fibrin deposition. Platelet-collagen adhesion in the two groups of patients was significantly higher than in healthy individuals (70.7 [61.2 to 82.0] and 70.3 [66.4 to 81.0] in types IIa and IIb patients, respectively, versus 51.2 [44.5 to 68.6] in control subjects; P < .05. All values are percent median [range]). In contrast, the thrombus volume was similar in the three groups (11.3 [8.0 to 13.0], 9.6 [6.4 to 15.3], and 10.2 [6.8 to 16.1] microns3/microns2 [range], respectively). Differences in fibrin deposition were not observed. Thus, it appears that platelet-collagen adhesion is augmented in patients with type IIa and IIb hyperlipoproteinemia, indicating that the process of thrombogenesis is hastened in these patients. PMID- 8218107 TI - Associations of age, adiposity, alcohol intake, menstrual status, and estrogen therapy with high-density lipoprotein subclasses. AB - We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the associations of age, adiposity, alcohol intake, and exogenous estrogen with high density lipoprotein (HDL) subclasses in 427 members of 51 principally Mormon kindreds. The absorbency of protein stain was used as an index of mass concentrations at intervals of 0.01 nm within five HDL subclasses: HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12 mm). Age and alcohol intake were obtained from questionnaires, and body mass index was computed from clinic measurements as weight (kg)/height (m)2. The results suggest that HDL3b concentrations were higher after menopause than before. Adult men (> or = 18 years old) had significantly higher HDL3c and HDL3b and significantly lower HDL2b and HDL2a levels than younger boys. Compared with the women, adult men had higher levels of HDL3c and HDL3b and lower levels of HDL2b, HDL2a, and larger-diameter HDL3a particles. There were no significant differences between the HDL profiles of women and younger boys, suggesting that divergence in HDL occurs during puberty. Eighty-eight percent of the increase in HDL associated with estrogen replacement in postmenopausal women occurred within HDL3a and HDL2a. Reported alcohol intake in adult men correlated with two HDL regions: one within the HDL2b region and a second within the HDL3a/2a region, whereas in women the positive correlation between alcohol and HDL levels was within the HDL2b region only. In both men and premenopausal adult women, increasing levels of body mass index were associated with higher levels of HDL3b and lower levels of HDL2b.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218108 TI - Lysophosphatidic acid enhances fibronectin binding to adherent cells. AB - 1-Oleoyl lysophosphatidic acid (LPA) enhanced binding of 125I-labeled fibronectin by cultured MG-63 osteosarcoma cells and human fibroblasts in monolayer cultures up to threefold over control levels. For osteosarcoma cells, LPA was minimally active at 0.1 ng/mL (0.2 nmol/L) and reached maximal activity at 10 ng/mL (20 nmol/L). Increased binding was evident within 10 minutes of treatment of cycloheximide-treated cells with LPA and was due to an increase in the number of fibronectin binding sites. LPA also increased the binding of a fragment containing the 70-kDa amino-terminal region of fibronectin that is primarily responsible for the reversible binding of fibronectin to matrix assembly sites on cell surfaces. Removal of LPA resulted in prompt return of fibronectin binding to baseline levels. These results indicate that LPA is an important enhancer of fibronectin-rich matrix deposition by cultured cells, and it may be the active component in serum and lipoprotein fractions that is responsible for enhancing fibronectin deposition. PMID- 8218109 TI - Cyclic AMP suppresses fibronectin expression in the rabbit aorta in vitro. AB - The effect of cAMP on the in vitro expression of rabbit aortic fibronectin was examined using a previously characterized organ culture system. Elevation of intracellular cAMP in incubated aortic rings by use of forskolin or dibutyryl cAMP (dbcAMP) inhibited the normally observed increase in fibronectin mRNA to levels below that found in unincubated tissue. The effect of dbcAMP on fibronectin mRNA was dose dependent and reversible. dbcAMP did not affect overall protein biosynthesis or the changes in collagen or elastin mRNAs that normally occurred during in vitro incubation, suggesting a selective regulatory effect on fibronectin. The inhibitory effect of dbcAMP on steady-state fibronectin mRNA levels was independent of the dibutyrate moiety, was not a result of cytotoxicity, did not require de novo protein synthesis, and did not appear to occur through a protein kinase A pathway. The data suggested that suppression of fibronectin mRNA levels potentially occurred via an indirect mechanism that may have involved a dbcAMP-induced reduction in intracellular calcium ([Ca2+]i) levels. The resultant decrease in [Ca2+]i may have affected fibronectin expression via a reduction in protein kinase C activity but did not depend on a calmodulin or calmodulin kinase I or II mechanism. PMID- 8218110 TI - Deletion of exon 15 of the LDL receptor gene is associated with a mild form of familial hypercholesterolemia. FH-Espoo. AB - We describe a mutation of the low-density lipoprotein (LDL) receptor gene, designated familial hypercholesterolemia (FH)-Espoo, which deletes exon 15 of the LDL receptor gene. The mutant receptor is predicted to lack 57 amino acids, including 18 serine and threonine residues, which are the sites of the clustered O-linked sugars of the receptor. Studies on 10 carriers of this gene revealed that FH-Espoo is associated with an exceptionally mild form of FH. Thus, in conditions in which cell proliferation was rendered dependent on the function of LDL receptors, lymphocytes from the patients with the FH-Espoo allele had a growth rate intermediate between those from healthy subjects and patients with the FH-Helsinki gene, a mutation known to abolish LDL receptor function. The in vivo fractional catabolic rate of LDL apolipoprotein B was lower than normal in the two FH-Espoo heterozygotes studied. Although higher than those in healthy controls, the serum LDL cholesterol concentrations in patients with the FH-Espoo gene were significantly lower than those in patients with the FH-Helsinki mutation. The thickness of the Achilles tendons was within the normal limits in subjects with the FH-Espoo gene. Our study suggests that moderate varieties of hypercholesterolemia, ie, those not considered to represent FH, may occasionally be due to subtle LDL receptor gene mutations. PMID- 8218111 TI - Distribution of lipid and raised lesions in aortas of young people of different geographic origins (WHO-ISFC PBDAY Study). World Health Organization International Society and Federation of Cardiology. Pathobiological Determinants of Atherosclerosis in Youth. AB - At the Morphometric Reference Center of the World Health Organization International Society and Federation of Cardiology PBDAY (Pathobiological Determinants of Atherosclerosis in Youth) project, we studied left hemiaortas of 5- through 34-year-old male and female healthy subjects who died of traumatic injury. The subjects were either of European, American, Asian, or African origin. Three hundred fifty-five thoracic and 343 abdominal left hemiaortas, stained and photographed at the Malmo, Sweden, World Health Organization Reference Center, were studied. Lipid and raised lesion extent was evaluated by using computerized techniques. Probability-of-occurrence maps of lipid and raised lesion distribution were obtained by image processing. Our data have shown that the distributions of atherosclerotic lesions in the aortic intimal surface, which were similar in the different ethnic groups, also prevailed in branching regions, where low-blood flow shear stress and turbulence occur. The areas involved by raised lesions and by lipid lesions only partially overlapped. Lipid lesion extent, which was different among the ethnic groups, continuously increased with age in males but not in females, in whom the increase ceased at an age range from 15 through 24 years. This suggests that ethnic and dietary factors influence the extent but not the distribution of atherosclerotic lesions in the human aorta. Probability-of-occurrence maps also provided evidence that not every fatty streak will develop into a raised lesion, or will not develop quickly. PMID- 8218113 TI - The prevention of infective endocarditis-paedodontic considerations. British Society for Antimicrobial Chemotherapy. AB - This review of the literature considers the pathology and epidemiology of infective endocarditis (IE), dental procedures that may precipitate IE and prophylaxis against dentally induced IE. The most recent recommendations published in May 1992 by the British Society for Antimicrobial Chemotherapy are outlined and discussed. PMID- 8218112 TI - Regulation of endothelial cell tissue factor expression by minimally oxidized LDL and lipopolysaccharide. AB - Tissue factor (TF) is the predominant physiological initiator of coagulation, and its regulation is a critical aspect of endothelial cell hemostatic function. This report describes the regulation of TF mRNA expression by two physiological agonists: minimally oxidized low-density lipoprotein (MM-LDL), which may modulate endothelial hemostatic function in atherosclerosis, and lipopolysaccharide (LPS), which is a mediator of septic shock. Northern blot analysis of total RNA from human endothelial cells exposed to either MM-LDL or LPS for varying times showed that TF mRNA increased sharply at 1 hour, peaked at 2 to 3 hours, and declined to basal levels by 6 to 8 hours after treatment. The half-life of TF mRNA in MM-LDL- and LPS-exposed endothelial cells was approximately 45 minutes and 40 minutes, respectively. The rate of TF mRNA degradation was similar at 1 and 4 hours after exposure in either MM-LDL- or LPS-stimulated endothelial cells. Nuclear runoff transcription assays showed a significantly increased rate of TF gene transcription in both MM-LDL- and LPS-exposed endothelial cells. Cycloheximide inhibited the induction of TF protein activity, but it enhanced the accumulation of TF mRNA in MM-LDL- and LPS-induced endothelial cells. These results indicated that regulation of TF expression by MM-LDL and LPS in human endothelial cells occurs principally at the level of gene transcription. PMID- 8218114 TI - Electromyographic changes resulting from orthodontic correction of Class III malocclusion. AB - This study measured the electromyographic (EMG) amplitudes of the interference pattern (IP) and the integrated EMG (IEMG) of the masseter and temporal muscles in 10 children with Class III malocclusion before, during, and after treatment with a myofunctional appliance (the monobloc), and compared the EMG values with those obtained from 10 children with Class I occlusion. The results showed that before treatment the mean amplitude values of IP were significantly higher in the Class III than in the Class I group. The mean amplitude values for IP activity in both muscles decreased during and after treatment; however, mean values of the IEMG activity did not show significant change for either muscle. These results are attributed to changes in the length of the muscle fibres as well as to neural modifications. This study demonstrates a non-invasive method that can be used to study the functional effects of orthodontic treatment. PMID- 8218115 TI - Radiovisiography--a preliminary subjective assessment in a hospital paediatric dentistry department. AB - Recent reports on radiovisiography (RVG) have concentrated mainly on the physical characteristics of this relatively new, digital imaging dental radiographic technique. This paper reports a preliminary assessment of the Mark 2 mobile system in routine use in a hospital paediatric dentistry department. The evaluation encompassed patient acceptability, ease of operation and the clinicians' subjective assessments of the images obtained. It was concluded that RVG is, in general, an acceptable alternative to conventional intra-oral radiography. PMID- 8218116 TI - Frequency of examination of children by dentists working under different payment systems in the United Kingdom. AB - The aims of this study were, first, to determine the frequency of dental examination of child patients by general dental practitioners working under a fee for-service or capitation payment system in eight areas of the United Kingdom and, secondly, to consider how the frequency of examination varied by dentist payment system, by area, by age of the child and by dentist. The number of examinations carried out by 198 general dental practitioners over a one-year period for 17,389 children aged 0-15 years was recorded. The mean number of examinations per year for children treated by dentists working under the fee-for service system was 1.7, and for those treated under the capitation system 1.6; this difference, although small, was statistically significant. The dentist and the age of the child were also shown to be related to the number of examinations but not the area in which the dentist worked. PMID- 8218117 TI - Observations on the use of rectally administered diazepam for sedating children before treatment of maxillofacial injuries: report of nine cases. AB - The use of diazepam in solution, administered per rectum, as an adjunct to treatment of paediatric maxillofacial injuries, has not been previously reported. Its use in a series of nine cases is described. The authors recommend this route of administration as an alternative form of management in the treatment of maxillofacial injuries in anxious children. PMID- 8218118 TI - Chronic headache and nocturnal bruxism in a 5-year-old child treated with an occlusal splint. AB - A report is presented of a 5-year-old girl who had an 11-month history of chronic headache and nocturnal bruxism. Treatment using a removable appliance that provided maximum support in centric relation was successful in relieving the headache during a follow-up period of 22 months. PMID- 8218119 TI - British Society of Paediatric Dentistry: a policy document on fissure sealants. PMID- 8218121 TI - [Ki 67 growth fraction in carcinomas and benign lesions of the breast]. AB - In 108 cases with benign breast lesions immunhistochemical studies using the monoclonal antibody Ki 67 yielded significantly lower values in comparison to 120 patients with breast carcinomas. The Ki 67 growth fraction showed a negative correlation with tumor size and nodal status and a positive correlation with tumor grading. The possible significance of this method performed on freeze sections in respect to the predictive estimation of nodal negative breast carcinomas and preneoplasias with indeterminate proliferative potential is emphasized. PMID- 8218120 TI - Nucleolar organizer regions in human breast cancer. AB - The silver staining technique for demonstration of argyrophilic nucleolar organizer regions (AgNORs) was examined for their usefulness in routine clinical diagnosis for discrimination of benign breast diseases from malignant ones and for prognostic purposes. We examined the number of AgNORs in 56 cases of malignant breast lesion and 20 cases of benign breast disease, using routinely fixed material. We found a clear-cut difference between benign breast diseases as compared with breast carcinomas where the mean AgNOR count was significantly higher, whereas no statistically significant correlation was observed between AgNOR counts and survival rate of human breast cancer patients. PMID- 8218122 TI - Evaluation of steroid hormone receptors with respect to tumor cellularity. AB - The cellularity grade of 350 carcinomas of the breast was determined in retrospect, and from these results 3 corrective factors were established. After biochemically assessing the concentrations of estrogen and progesterone receptors, these were compared with tumor size, histological type and cellularity. As expected, ductal carcinomas showed higher average hormone receptor concentrations than lobular or medullary carcinomas. There was no evidence of a positive correlation between receptor concentration and cellularity grade. Many times, an initially negative receptor status in the lobular carcinomas with their relative paucity of cells was modified to a positive status. Accordingly, further possible therapeutic approaches should be discussed with respect to tumor cellularity. PMID- 8218123 TI - Nuclear morphometry as a prognostic factor in laryngeal squamous cell carcinomas. Preliminary study. AB - A preliminary report concerning the prognostic significance of certain nuclear morphometric parameters in laryngeal squamous cell carcinoma (SCC) is presented. 18 cases of primarily glottic laryngeal SCC were graded according to the criteria outlined by Jakobsson et al., and assessed for the presence of infiltration of laryngeal cartilage. Nuclear width (short axis) and perimeter were found to be smaller in the "favourable prognosis" group than in the "unfavourable prognosis" one, on an indicative basis only, due to the small number of cases. The nuclear perimeter was furthermore found to be larger in cases with carcinomatous infiltration of the laryngeal cartilage than in cases without, on a statistically highly significant basis. The clinical utility of these results in a biopsy report of a laryngeal SCC is discussed. PMID- 8218124 TI - The association of pulmonary CMV infection with interstitial pneumonia after bone marrow transplantation. Histopathological and immunohistochemical findings in 104 autopsies. AB - Lung tissue of 104 necropsies was studied by routine (HE) histology, by immunohistochemistry and partly by in situ hybridization in order to explore the association of pulmonary cytomegalovirus (CMV) infection and interstitial pneumonia (IP) after allogeneic bone marrow transplantation. IP was detected in 59 of 104 patients (56%). 12 of these (20% of the IP cases) presented as CMV-IP. No evidence of a CMV infection was obtained in the remaining 47 IP. Immunohistochemistry did not improve the CMV detection essentially over the results of routine (HE) analysis of viral inclusions. In situ hybridization performed on frozen sections of 21 cases turned out to be more sensitive than routine histology and immunohistochemistry, detecting active as well as latent CMV infections. However, the clinical relevance of latent infections, as disclosed by positive hybridization results in the absence of nuclear inclusions as well as immunohistochemical positivities, seems to be low, because latent infections typically were not found to be associated with IP. PMID- 8218125 TI - [Pathomorpholigical findings in ketothiolase deficiency]. AB - The post-mortem findings in two brothers who had suffered from clinically and biochemically confirmed ketothiolase deficiency are reported. They had died as a consequence of metabolic-acidotic crisis at the age of 6 years and 9 months and 4 years and 1 month, respectively. Autopsy revealed cardiac hypertrophy and brain pathology in both children. The latter consisted of loss of neurons, spongiosis and slight reactive astrocytosis affecting parasagittal areas of the parietal and occipital cortex, visual cortex, putamen, caput nuclei caudati and claustrum. Furthermore demyelination of the visual pathways, including chiasma opticum, was seen. Changes in both hemispheres were almost symmetric. In the younger child, changes were less severe than in the older one in whom the course of the disease had been longer. To the best of our knowledge this is the first report of autopsy findings in siblings with ketothiolase deficiency. PMID- 8218126 TI - [A combination of spermatocytic and classic seminoma, mature teratoma and carcinoma in situ of the testis. An attempt at an etiologic explanation]. AB - We report of a 39 years old patient with a large testicular tumor found during an examination for infertility. The tumor consisted of a spermatocytic seminoma (SS) and a differentiated teratoma (TD). Furthermore, two small foci of seminoma were seen in the surrounding testicular tissue, several testicular tubuli contained carcinoma in situ (CIS). The diagnosis was based on the results obtained with various immunohistochemical markers: keratin, vimentin, desmin, LCA, CD3, CD20, CD45R, ferritin, PLAP, AFP. On the basis of the macroscopic and histopathological features, we propose the following etiology: CIS progressed in an earlier phase to the (larger) TD and later to the (smaller) classical seminoma; likewise, in an earlier phase, SS developed from a still unknown precursor stage. Our case of a mixed tumor as well as other cases reported in the last years do not allow the explanation of a differing etiology for SS. On the contrary, it may be presumed that the origins of seminoma and teratoma on the one hand and SS on the other hand are less divergent than hitherto thought. PMID- 8218127 TI - Gliomatosis cerebri. Clinical, neuropathological, immunohistochemical and morphometric Studies. AB - Clinico-neuropathological findings recorded from one case of cerebral gliomatosis are reported in this paper. Immunocytochemical methods (GFAP, protein S-100) were used together with morphometric computer-assisted analysis for more effective investigation of certain cytopathological features such as the relationship between cerebral gliomatosis and low-graded astrocytoma. Immunohistochemically, most of the proliferating cells were positive to GFAP and/or to protein S-100, which was in fair agreement with publications elsewhere in the literature. However, varying amounts of spindle-shaped cells remained unstained. The nature of such cells is unclear. The morphometric study showed the majority of cellular parameters of cerebral gliomatosis to be comparable to cellular parameters recordable from "peripheral" regions of a series of low-grade astrocytomas. PMID- 8218128 TI - [History of prosector's department at Charite of Berlin. 4. Benno Hernst Heinrich Reinhardt, Prosector of Charite, 1849 to 1852]. AB - This communication has been devoted to BENNO ERNST HEINRICH REINHARDT'S brief period of office (1849-1852) as Prosector of Berlin's Charite Hospital. REINHARDT who was born in Neustrelitz, Mecklenburg-Western Pomerania, studied medicine in Berlin and Halle. His predilection for microscopy dated back already to that period. Having returned to Berlin in 1844, he took his doctor's degree in that year. Also in 1844, he became assistant to the gynaecologist, CARL MAYER (1795 1858), and opened a medical practice of his own. In 1848, he joined a cholera hospital in Berlin. In that year, he qualified and obtained the (unsalaried) status of university lecturer. In 1849, he had a short-time assignment as a supplementary physician at the Berlin University Hospital in Ziegelstrasse before he succeeded RUDOLF VIRCHOW (1821-1902) as Prosector of the Charite Hospital on 1 October. REINHARDT'S second period of life in Berlin was characterized by a close friendship with RUDOLF VIRCHOW which lasted also over the years VIRCHOW spent in Wurzburg, until REINHARDT'S early death. As a consequence of his short scientific life, he has left only a few printed publications which were more or less sketchy. Until our days, his name has been associated with "VIRCHOWS Archiv" which was founded jointly by him and VIRCHOW in 1847. REINHARDT had contracted tuberculosis in 1846. When he took office, his illness had already progressed so that his influence on the further development of the prosector's office had to remain a limited one. After a mere 2 1/2 years in office, he succumbed to his illness on 11 March 1852. After his death, RUDOLF LEUBUSCHER (1821-1861) collected his unpublished papers and those in preparation and published them still in that year, under the title "BENNO REINHARDT'S pathologisch-anatomische Untersuchungen". PMID- 8218129 TI - Precordial isopotential electrocardiographic mapping and its clinical use in patients with ischaemic heart disease. AB - After ten years of experience, the authors present an overview of the possible clinical uses of precordial isopotential electrocardiographic mapping in patients with ischaemic heart disease. The resting Q wave and ST segment maps have most often been found useful in the early phases of myocardial infarction. They are a helpful tool for monitoring progression of the disease, the effect of drugs, or the therapeutic effect of fibrinolytic therapy, etc. R wave mapping provides an excellent opportunity for following up patients after orthotopic heart transplantation and monitoring cardiac rejection. Stress tests are usually performed under a workload; alternative loads may be mental, pharmacological, stimulation-induced or under hypoxaemic stress. To evaluate a test, resting values are compared with those obtained during exercise. It is mainly exercise ST segment maps which have proved to be most informative; their use in the chronic phase of ischaemic heart disease helps to make the diagnosis of coronary insufficiency more accurate. In clinical practice, stress tests are recommended mostly in the follow-up of drug therapy, monitoring of the therapeutic effect of cardiac surgery or coronary angioplasty. PMID- 8218130 TI - Analysis of ventricular activation in patients with chronic non-Q wave myocardial infarction: comparison with left ventricular asynergy and myocardial perfusion defects. AB - In this report, we dealt with ventricular activation abnormalities in 30 patients with previous non-Q myocardial infarction (MI) by means of the CARDIAG 128.1 device, which enables analysis of ECGs, VCGs and body surface potential maps. The diagnosis was verified by left ventriculography, echocardiography and perfusion scintigraphy. Twenty-nine healthy subjects served as the control group. Morphological findings confirmed the presence of a significant subgroup with serious left ventricular asynergy. Seven electrocardiological variables, which significantly differed from control values, disclosed that non-Q MI is responsible for localized activation time prolongation, and that inferoposterior scars tend to delay the entire activation of ventricles, and to cause disturbances of the terminal depolarization phase together with a decrease in voltage production during QRS. Lesions of the anterior wall and the apicomesial part of the inferoposterior wall affect the distribution of the Q wave more often than the posterior basal ones. The probability of such abnormalities increases with the degree of asynergy. Some VCG criteria increase the sensitivity of electrocardiological analysis. These parameters will be used for evaluating the diagnostic value of electrocardiological analysis in the chronic non-Q MI. Non-Q myocardial infarctions represent a heterogeneous group of infarctions from both electrophysiological and morphological aspects. PMID- 8218131 TI - Quantitative evaluation of body surface potential mapping of heart electrical field in ischaemic heart disease. AB - New possibilities of quantitative evaluation of body surface potential mapping were studied in 78 patients with ischaemic heart disease. Integral maps of the Q wave, QRS and ST-T intervals were plotted and isochronous maps of ventricular activation time and maps of asynchronous potential minima of the Q wave were determined. Minimum and maximum potential values and their time relations were evaluated in the maps. Left ventricular contraction abnormality detected by left ventricular angiography was determined by a point score and expressed as an index of asynergy. The number of coronary artery branches with significant narrowing was assessed and the extent of coronary artery damage was evaluated by an arbitrary defined index. Using quantitative parameters from the maps, multiple stepwise linear regression was performed. The relationship between map parameters and index of asynergy corresponded to multiple correlation coefficient r = 0.69 (p = 0.01) in the whole group of patients. In the group of patients with left ventricular contraction abnormality the relationship between these parameters was found to be r = 0.87 (p = 0.01). The relationship between map parameters and the number of coronary artery branches with significant stenosis was r = 0.60 (p = 0.01) in the group of patients with positive coronary angiography. In the same group of patients the relationship between map parameters and the index evaluating coronary artery damage was equal to r = 0.63 (p = 0.01). The data obtained from body surface integral maps enable to quantify cardiac ischaemic damage. PMID- 8218132 TI - Repolarization pattern of body surface potential maps (BSPM) in coronary artery disease. AB - The aim of our study was to assess if repolarization BSPM were able to evaluate the site, size and severity of chronic ischaemic damages and if BSPM were in any way related to the regional attenuation of myocardial contractility or to the site of coronary artery occlusion. The BSPM were obtained from 69 patients suffering from coronary artery disease confirmed by coronarography, with at least 75% occlusion of at least one coronary artery. According to the site of single occlusion, or a combination of the sites of multiple occlusions, the patients were divided into 6 subgroups. According to the region of attenuated kinetics the same group of 69 patients was also divided into other 6 subgroups. As in the polarity distribution there was only a limited accordance in BSPM with coronarographic and echocardiographic findings, in the localization of extreme values there were very important specific changes in patients with normal kinetics as determined by both contrast ventriculography and two-dimensional echocardiography. The repolarization maps can distinguish patients with coronary artery disease and normal echocardiography from healthy persons with a sensitivity of 85% and a specificity of 65% in the case of the isoareal map from the ST segment (RIAM) and 90% and 85%, respectively, in the case of the isointegral map from the whole ST-T segments (RIIM). PMID- 8218133 TI - Body surface potential mapping (BSPM) before and after percutaneous transluminal coronary angioplasty (PTCA). AB - The departure index area of departure maps before and after the PTCA procedure was evaluated in 10 randomly chosen patients with clinically significant ischaemic heart disease. The body surface mapping system CARDIAG 128.1, (ZPA Prague-Cakovice) was used. The departure index was calculated using Kubota's formula. The departure indexes of the ST-T interval and departure maps of 36 ms and 80 ms intervals from the J point were followed. A decrease of the departure index area was considered as a sign of successful PTCA. A correct classification was made in 6 patients out of 9 (66%) with successfully performed PTCA. The identification of one patient with unsuccessful PTCA procedure was also correctly determined. The overall correlation between the effect of PTCA and the departure index area change was 7 out of 10 (70%). The authors consider this method to be a useful non-invasive method for identifying of successful or unsuccessful PTCA in patients with coronary artery disease. PMID- 8218134 TI - Diagnostic value of body surface mapping in the Wolff-Parkinson-White (WPW) syndrome. PMID- 8218135 TI - Contemporary body surface potential mapping in electrocardiology and its perspectives. PMID- 8218136 TI - Spatial and temporal informations from the cardiac electric field. AB - Cardiac excitation generates an electric field which projects onto the body surface. This allows the information about the heart to be obtained noninvasively as a physical process. Thus the analysis of the cardioelectric field requires spatial, spatio-temporal and temporal approaches. The spatial approach resolves the distribution of the field in the body in relation to the configuration of the source by means of constructing a field map for one instant. This reflects the anatomical background. The spatio-temporal analysis includes the events of activation and repolarization, provides a series of maps or compressed presentations and comprises the dynamics of the cardiac excitatory cycle. The temporal access investigates the generation of the cardiac rhythm. It utilizes the analysis of sinus arrhythmia and the frequency analysis of heart rate variability. The results reflect efferent mechanism of chronotropic control as well as afferent and central management of informations relevant for cardiac control. PMID- 8218137 TI - Problems and perspectives of mapping the cardiac electric field. AB - The cardiac electrical field is important not only because of its diagnostic significance, but also as a biological and biophysical phenomenon. As such, it has become a research target of biologists, biophysicists and biomathematicians. It has also been an impetus for constructing more and more sophisticated measuring devices. Criteria for the diagnostic evaluation of body surface potential maps have often been derived from clinical studies based on a restricted number of cases. Further clinical research is therefore a conditio sine qua non for the acceptance of mapping as a routine diagnostic procedure. In the future, body surface potential distributions will be used as the input for computer simulation of potential distribution and activation chronograms on the geometric surface closely encompassing the heart. In such a way, electrocardiographic signals will be interpreted in terms of activation and repolarization sequences on the cardiac surface. PMID- 8218138 TI - Cardiac micropotentials reached from one systole as non-dipolar residue by singular value decomposition. AB - Cardiac micropotentials are considered to have a predictive value in critical ventricular tachycardia or sudden death. These micropotentials are obtained by numeric filtration of the result of sequential averaging of about 200 systoles (i.e. of measurement at about 3 min interval) which is significantly influenced by known intraindividual ECG variability. It follows from our previous studies that the non-dipolar residue (i.e. the sum of all components of an equivalent source of the heart electrical field with the exception of the first three dominant dipolar components) corresponds by its nature to the cardiac micropotentials, i.e. to late potentials. Verification of this hypothesis utilizing singular value decomposition and replacing the sequential averaging by "surface" averaging of the matrix of synchronously measured ECGs is the aim of this project. The results of the present study can be considered as a confirmation of this hypothesis. These results provide a better understanding of the structure of the body surface potential distribution and for clinical purposes they make it possible to attain cardiac micropotentials (late potentials) from one systole. PMID- 8218139 TI - Mapping of activation, recovery and activation-recovery intervals in the human heart. AB - Peroperative epicardial mapping of activation, recovery and activation-recovery intervals in the human heart has been performed in a group of 12 patients. These patients had the coronary disease but electrocardiograms with normal characteristics. For this mapping, 240 unipolar electrograms were simultaneously recorded with the system SATAPEC built in our laboratory. The results confirm the classical data obtained on the dog heart. In particular, it was well established that the duration of activation corresponding to activation-recovery intervals is shorter at the base than at the apex of the posterior surface of the heart. With SATAPEC it is very easy to obtain epicardial mapping of electrical activity in a few minutes during open heart surgery. PMID- 8218140 TI - Usefulness of body surface potential mapping for clinical diagnosis and research. PMID- 8218141 TI - The methodology of clinical analysis of electric heart field. AB - A brief description of the methodology of analysis of the electric heart field using electrocardiograms, vectorcardiograms, diagrams of potential maxima/minima and body surface potential maps is presented. The text is focused on the description of different kinds of isopotential and isointegral maps and their diagnostic possibilities. A detailed description of the diagram of potential maxima/minima and its place in diagnostic of different disturbances of the heart muscle and conduction defects is given. PMID- 8218142 TI - Comparison of discriminant analysis and probabilistic expert system in VCG data classification. AB - Our previous studies (Valova et al. 1992) have dealt with the possibilities of expert system utilization for electrocardiologic data interpretation. The results obtained in these studies provided evidence that the selected probabilistic expert system is suitable for the solution of VCG data interpretation problems. The aim of this paper was to compare the results obtained by stepwise discriminant analysis with that obtained by a probabilistic expert system. These classification methods were applied to VCG data measured by Frank's lead system. Five groups of patients were investigated: 76 healthy subjects, 36 patients with angina pectoris, 112 patients with old posterior myocardial infarction, 107 patients with old anterior myocardial infarction and 35 patients with old anteroseptal myocardial infarction. The classification was carried out by the leaving-one-out technique. Results of the classification obtained in five groups by a probabilistic expert system are evidently better than those obtained by stepwise discriminant analysis. PMID- 8218143 TI - Computer processing of the orthogonal electrocardiogram and vectorcardiogram. AB - The aim of this contribution was to review the possibilities of presentation of orthogonal ECG signals and to evaluate the progress in computerized electrocardiography achieved in Czechoslovakia. The information about the cardiac electric field in orthogonal electrocardiogrpahy is defined and consequently displayed as a fixed single dipole (vector). The spatial trajectory of vector end point (spatial vectorcardiographic loop) can be presented in different ways--as orthogonal electrocardiogram, polarcardiogram, planar vectorcardiogram and decartogram, respectively. The advantages of particular methods of presentation, as well as their limitations are discussed. Computer-assisted electrocardiography was introduced in Czechoslovakia in 1974. The original AVA program has been further developed in the Research Institute of Medical Informatics (formerly Research Institute of Medical Bionics). The currently developed system CardioSys allows the utilization of all the possibilities of orthogonal ECG and vectorcardiographic presentation for clinical and epidemiological cardiology as well as for the research. PMID- 8218144 TI - Body surface isochrone maps of peak R in normal adolescent girls. AB - The aim of our study was to evaluate the adequacy of a new mapping device for obtaining a reliable set of normal maps characteristic for this approach. We studied body surface isochrone maps of peak R in four healthy adolescent girls using the mapping system CARDIAG 128.1 with 80 unipolar leads placed in a regular grid. The constructed maps were compared with published data using 10 criteria. None of the maps obtained could be regarded as normal. After evaluating the reasons for the "abnormality", we assume that they could be caused mostly by the processing of signals. This fact can be eliminated by improving the existing software. PMID- 8218145 TI - Critical issues of developmental seizure disorders. PMID- 8218146 TI - Cerebral energy state of neonatal rats during seizures induced by homocysteine. AB - Seizures were induced in 7-day-old rats by intraperitoneal injection of DL homocysteine thiolactone. Phosphocreatine (PCr), ATP, glucose, glycogen and lactate were determined in the cerebral cortex during various intervals after injection, corresponding to the early, as well as long periods of seizure activity. The unchanged levels of ATP, a very mild PCr decline and a pronounced accumulation of lactate (in the face of modest changes in brain glucose and glycogen) were observed. These results suggest that the immature rat brain is able to compensate energy expenditure associated with seizure activity by increased energy production, mainly due to increased anaerobic glycolysis. It remains to be determined whether a similar conclusion is also valid for other brain regions, e.g. subcortical structures. PMID- 8218147 TI - Effect of postischaemic recirculation on DNA synthesis in vulnerable rat brain regions. AB - Incorporation of labelled thymidine into DNA of different rat brain regions was studied after 30 min of forebrain ischaemia and recirculation periods up to 24 hours. The amount of label incorporated into DNA showed a different pattern in the brain. After 1 hour of recirculation, the incorporation was reduced in the cortex and in the striatum, without any significant change in the hippocampus. After 3 to 9 hours the incorporation remained depressed in the cortex, diminished in the hippocampus, and increased by 2-2.5 fold in the striatum. Later, after 24 hours, the DNA labelling returned to control values in the striatum and in the cortex, but was increased in the hippocampus. PMID- 8218148 TI - Changes of pineal N-acetyltransferase activity in gamma irradiated rats. AB - Male Wistar rats were exposed to whole body irradiation with 14.35 Gy gamma rays after the adaptation to light/dark cycle (LD 12:12). Three groups of rats were examined: A) rats irradiated in the night and placed in the 12 h LD cycle again, B) rats irradiated in the day-time and placed in the 12 h LD cycle, and C) rats irradiated in the night and kept in constant darkness. All analyses were carried out in the dark. Radiation enhanced the activity of pineal N-acetyltransferase 3 4 days after exposure in all groups, in the C group significantly on the 4th day. Different light regimens during and after irradiation did not to affect the activity of this key enzyme of melatonin synthesis substantially. PMID- 8218149 TI - Anterior pituitary weight, cAMP, cGMP and prolactin levels after combined treatment with estradiol and methylene blue. AB - Male rats received estradiol benzoate in a long acting microcrystalline suspension (1 mg/rat i.m., twice a week), methylene blue (MB) 0.5% in the food and the combination of estradiol and MB. After three weeks, MB partially inhibited the growth response of the anterior pituitary to estradiol and it partially inhibited the increase of cAMP content in anterior pituitary. The increase of anterior pituitary cGMP content was not modified by MB, neither the ratio cAMP/cGMP in the anterior pituitary which, however, decreased after estradiol. This decrease was not modified by MB. On the other hand, the prolactin (PRL) increase in the blood after estradiol was inhibited by MB, although the prolactin content in the anterior pituitary was not. Methylene blue alone did not change blood prolactin concentration, but it unexpectedly elevated blood thyroxine levels and this effect was partially inhibited by simultaneous estradiol treatment. PMID- 8218150 TI - Effect of the oyster fungus on glycaemia and cholesterolaemia in rats with insulin-dependent diabetes. AB - We have investigated the effect of a diet containing of 4% oyster fungus (Pleurotus ostreatus) and 0.1% cholesterol on glycaemia and hyperlipoproteinaemia in rats with insulin-dependent diabetes (streptozotocin 45 mg/kg). After two months, the rats with diabetes kept on the oyster fungus diet, had a significantly lower basal and postprandial glycaemia, the insulinaemia remained unchanged. The cholesterol concentration was decreased by more than 40%, the lipoprotein profile was upgraded by the decrease of the cholesterol in both the low density and very low density lipoproteins. The oyster fungus decreased the cholesterol accumulation in the liver and had no significant effects on the levels of serum and liver triacylglycerols. PMID- 8218151 TI - Red cell ouabain-resistant Na+ and K+ transport in Wistar, brown Norway and spontaneously hypertensive rats. AB - Our previous studies concerning the role of furosemide-resistant cation leaks in genetic hypertension demonstrated that blood pressure of recombinant inbred strains (derived from F2 hybrids of spontaneously hypertensive and normotensive Brown Norway rats) cosegregated with inward Na+ leak (determined in saline medium) but not with Na+ efflux (measured in Mg(2+)-sucrose medium) or with Rb+ uptake (found in either medium). In the present study the alterations of particular components of ouabain-resistant (OR) Na+ and K+ (Rb+) transport in erythrocytes of spontaneously hypertensive rats (SHR) were analyzed using saline and Na(+)-free (Mg(2+)-sucrose or choline) incubation media. OR Na+ net uptake was elevated in SHR as compared to both normotensive strains--Brown Norway and Wistar rats. This was mainly due to an increased bumetanide-resistant (BR) Na+ inward leak. On the other hand, Wistar rats did not differ significantly from SHR in either OR Na+ efflux or OR Rb+ uptakes. Major augmentations of BR Na+ efflux and BR Rb+ uptake in SHR erythrocytes were seen not only in Mg(2+)-sucrose medium but also in choline medium. In both Na(+)-free media there was a considerable saturable Na+i-dependent component of BR Na+ and Rb+ fluxes which was more pronounced in SHR than in BN erythrocytes. A great caution is required for the interpretation of the data on "increased passive membrane permeability" obtained in SHR erythrocytes incubated in Na(+)-free media because of the presence of this saturable component which seems to be related to incompletely inhibited Na(+)-K+ pump.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218153 TI - Renewal of DNA in Purkinje cell nuclei of mouse cerebellum. A 9-month follow-up autoradiographic study. AB - 3H thymidine was injected into pregnant mice in order to label the DNA in the dividing Purkinje cell (PC) precursors of the embryonic cerebellum. The retention of 3H-DNA was evaluated in PC nuclei of animals at the age of 25 days, 3, 6 or 9 months by light microscope autoradiography. The number of silver grains decreased in the whole nuclei by 13.6% and 19.6% in animals 6- and 9-month-old, respectively. In the nucleolar region, the loss of DNA radioactivity was more profound; the silver grain counts decreased by 22.6% and 29.1% in 6- and 9-month old animals, respectively. No significant differences in the volume and dry mass concentration were found in the PC nuclei of 25 PD and 9 PM old animals. Therefore, the observed changes in grain density counts represent the actual measure of 3H-DNA loss, and/or "spontaneous" renewal of the DNA molecule in PC nuclei, as well as its higher expression in the nucleolar region. Furthermore, it follows from the comparison of our data with those present in the literature, that DNA synthesized in nerve cell precursors before their withdrawal from the mitotic cycle is more stable than that synthesized in postmitotic neurones. This suggests that the repair of DNA in mature neurones might be of an error-prone type. PMID- 8218154 TI - Perinatal hypoxia suppresses immune response of adult rats. AB - We tested the effect of perinatal (one week prenatal and one week postnatal) normobaric hypoxia on the immune response of rats in their 9th week of life. We found that perinatally hypoxic rats produced less serum antibodies after sequential immunization with ovalbumin and sheep red blood cells. Also phagocytosis of HEMA microparticles by neutrophil leukocytes from perinatally hypoxic rats was depressed as well as the oxidative burst of their peritoneal macrophages and neutrophils. These results demonstrate that perinatal hypoxia has an important effect on the immune system of the rat. PMID- 8218155 TI - The influence of age on the development of two-kidney, one-clip hypertension in the rat. AB - The role of age in the development of two-kidney, one-clip (2K1C) renal hypertension was evaluated. Blood pressure response to aortic constriction was more pronounced in young rats although the alterations of renal renin activity and body fluid volumes were greater in adult ones. Obtained results suggested that 2K1C renal hypertension is maintained by reciprocal interaction of renin angiotensin system and body fluid volume alterations only in adult rats. In young rats other factors might be more important. PMID- 8218156 TI - Age-dependent changes of baroreflex efficiency in Dahl rats: effects of high salt intake. AB - The age-dependent changes in baroreflex control of heart rate were studied in inbred Dahl rats. At the age of 8 weeks the baroreflex slope was significantly greater in salt-resistant (R/Jr) than in salt-sensitive (S/Jr) rats fed a low salt diet. The reverse was true in 16-week-old animals. High salt intake (8% NaCl diet for 4 weeks) suppressed baroreflex efficiency in both age groups of S/Jr animals whereas no effects occurred in R/Jr rats. Baroreflex slope was, however, significantly lower in young S/Jr rats with a severe form of salt hypertension than in adult salt-loaded S/Jr rats in which only a moderate blood pressure elevation was observed. PMID- 8218157 TI - Elevation of rat brain superoxide dismutase activity after combined high altitude hypoxia and ascorbic acid treatment. PMID- 8218158 TI - Pressure-induced dissociation of fluorescein from the anti-fluorescein single chain antibody 4-4-20. AB - Hydrostatic pressure was used to dissociate fluorescein (Fl) from the high affinity anti-Fl single-chain antibody 4-4-20 (SCA 4-4-20). Fl dissociation was monitored by measuring (1) the shift in the Fl absorption peak, (2) the recovery in Fl fluorescence intensity, which is quenched upon SCA binding, or (3) the decrease in Fl fluorescence polarization. Pressure effects were studied at two different Fl:SCA 4-4-20 molar ratios: 1:1, at which Fl fluorescence quenching was ca. 35% at atmospheric pressure, and 1:5, at which quenching reached 95-97% under the same conditions. In both cases, pressure-induced dissociation was favored by concomitant dilution of protein and ligand. Dissociation constants (KD) at each pressure were calculated on the basis of measurements of Fl fluorescence polarization under pressure. The dependence of KD, and consequently of delta G of dissociation, on pressure permitted calculation of the magnitude of the standard volume change (delta V) involved in the dissociation process. According to this study, delta V of dissociation for the Fl-SCA complex is -50 mL/mol, which corresponds to a 10-times higher value than that found for dissociation of Fl from the intact IgG mAb 4-4-20 [Herron, J. N., Kranz, D. M., Jameson, D. M., & Voss, E. W., Jr. (1986) Biochemistry 25, 4602-4609]. This difference is explained in terms of a higher overall flexibility of unliganded SCA and of a less stable binding site in SCA relative to mAb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218159 TI - Amino acids of the recombinant kringle 1 domain of human plasminogen that stabilize its interaction with omega-amino acids. AB - A series of strategically designed recombinant (r) mutants of the kringle 1 region of human plasminogen ([K1HPg]) have been constructed and the resulting gene products employed to reveal the identities of the residues that contribute to stabilization of the binding of omega-amino acid ligands to this domain. On the basis of determinations of the binding constants of the ligands, 6 aminohexanoic acid and trans-4-(aminomethyl)cyclohexane-1-carboxylic acid, to a variety of these mutants, we find that the anionic site of the polypeptide responsible for stabilization of the amino group of the ligands consists of both D54 and D56 and the cationic site of the polypeptide that interacts with the carboxylate group of the ligand is composed solely of R70. The main hydrophobic interactions that stabilize binding of these ligands, likely by interactions with the ligand hydrophobic regions, are principally due to W61, Y63, and Y71. The results obtained are consistent with conclusions that could be made from analysis of the X-ray crystal structure of r-[K1HPg] and from previous studies from this laboratory regarding the binding of ligands of this type to the kringle 2 region of tissue-type plasminogen activator ([K2tPA]). It thus appears as though a common ligand binding site has evolved in different kringles with ligand specificity differences between r-[K2tPA] and r-[K1HPg] perhaps explainable by the different nature of the cationic sites on these polypeptides that are involved in coordination to the ligand carboxylate groups. PMID- 8218160 TI - Structure and energetics of a non-proline cis-peptidyl linkage in a proline-202- >alanine carbonic anhydrase II variant. AB - The crystal structure of a human carbonic anhydrase II (CAII) variant, cis proline-202-->alanine (P202A), has been determined at 1.7-A resolution, indicating that the wild-type geometry, including the cis-peptidyl linkage, is retained upon substitution of proline by alanine. The CO2 hydrase activity and affinity for sulfonamide inhibitors of P202A CAII are virtually identical to those of wild type. However, the substitution of cis-alanine for cis-proline decreases the stability of the folded state by approximately 5 kcal mol-1 relative to both the unfolded state and an equilibrium intermediate in guanidine hydrochloride-induced denaturation. This destabilization can be attributed mainly to the less favorable cis/trans equilibrium of Xaa-alanine bonds compared to Xaa proline bonds in the denatured state although other factors, including increased conformational entropy of the denatured state and decreased packing interactions in the native state, also contribute to the observed destabilization. The high catalytic activity of P202A CAII illustrates that unfavorable local conformations are nonetheless endured to satisfy the precise structural requirements of catalysis and ligand binding in the CAII active site. PMID- 8218161 TI - How the anti-(metal chelate) antibody CHA255 is specific for the metal ion of its antigen: X-ray structures for two Fab'/hapten complexes with different metals in the chelate. AB - Antibodies with bound metal-chelate haptens provide new means for exploiting the diverse properties of metallic elements. The murine monoclonal antibody CHA255 (IgG1 lambda) binds the metal-chelate hapten indium (III)-4-[N'-(2 hydroxyethyl)thioureido]-L-benzyl-EDTA (designated In-EOTUBE) with high affinity (K(a) = 1.1 x 10(10) M-1). Antibody binding is highly specific for the indium chelate; the affinity decreases as much as 10(4) with other metals, even those having ionic radii close to indium. To better understand this selectivity, the crystal structure of the antigen-binding fragment (Fab') of CHA255 complexed with its hapten, In(III)-EOTUBE, was determined by molecular replacement and refined at 2.2-A resolution. The structure of CHA255 Fab' complexed with Fe(III)-EOTUBE was also determined and refined at 2.8-A resolution. In both structures, the hapten's EDTA moiety is half-buried near the center of the complementarity determining regions (CDR's). Five of the six CDR's on the Fab' interact with the hapten through protein side-chain atoms (but not main-chain atoms). A novel feature of the In-EOTUBE/Fab' complex is coordination of the indium by N epsilon of one histidine from the heavy chain's third CDR (distance = 2.4 A). The histidine coordination is not observed in the Fe-EOTUBE/Fab' complex, due mainly to a slightly different hapten conformation that reduces metal accessibility; this may partially explain the 20-fold lower affinity of CHA255 for iron hapten. An unexpected feature of the Fab' overall is an elbow angle of 193 degrees (the angle between the pseudodyad axes of the Fab's constant and variable domains). PMID- 8218162 TI - Conformational backbone dynamics of the cyclic decapeptide antamanide. Application of a new multiconformational search algorithm based on NMR data. AB - A general procedure for the analysis of biomolecular structures by NMR in the presence of rapid conformational dynamics has been applied to the study of the cyclic decapeptide antamanide. Two-dimensional experiments, relaxation measurements in the rotating frame, and homo- and heteronuclear coupling constant determinations have been used to characterize the dynamic properties of the molecule, in combination with a novel search algorithm for investigating multiconformational equilibria. Direct evidence for the presence of a conformational exchange process with an activation energy of approximately 20 kJ mol-1 and an exchange lifetime of approximately 25 microseconds at 320 K has been obtained from rotating frame relaxation measurements. This evidence is combined with the information derived from the multiconformational search algorithm MEDUSA to propose sets of structures that coexist in a dynamic exchange equilibrium. PMID- 8218163 TI - Structure and dynamics of barnase complexed with 3'-GMP studied by NMR spectroscopy. AB - The binding of 3'-GMP to the ribonuclease, barnase, has been studied using heteronuclear 2D and 3D NMR spectroscopy. The 1H and 15N NMR spectra of barnase complexed with 3'-GMP have been assigned. 2D and 3D NOESY spectra have been used to identify inter- and intramolecular NOEs, and a solution structure for the barnase-3'-GMP complex has been calculated. The position of the guanine ring of the ligand is reasonably well defined in the structures. The guanine ring forms hydrogen bonds with the NH protons of Ser57 and Arg59. These residues are located in a loop that is conserved among the microbial guanine-specific ribonucleases. The 2'-hydroxyl of 3'-GMP is close to His102 and Glu73, which have been shown to be involved in catalysis. The phosphate group of 3'-GMP is close to a number of positively charged residues that have also been shown to be important for activity. The position of the sugar moiety of 3'-GMP is less well defined in the structures. Structures calculated for the complex could not simultaneously satisfy all the observed intermolecular NOEs for the sugar protons, suggesting that the sugar samples several conformations when bound to barnase. The binding of 3'-GMP to barnase in solution is similar to that observed in the crystal structures of nucleotides bound to related ribonucleases. 3'-GMP binding causes no major conformational change in barnase. In contrast to the small structural changes that occur, there is a significant decrease in the rates of hydrogen/deuterium exchange and aromatic ring rotation in the active site of barnase upon ligand binding. PMID- 8218164 TI - Proton NMR studies of noncovalent complexes of cytochrome c peroxidase-cyanide with horse and yeast ferricytochromes c. AB - Noncovalent complexes of cyanide-ligated cytochrome c peroxidase with horse ferricytochrome c and yeast isozyme-1 ferricytochrome c have been formed in 10 mM potassium nitrate salt solutions and studied by proton NMR spectroscopy. The chemical shifts in the ferricytochrome c spectrum induced by complex formation with low-spin, cyanide-ligated cytochrome c peroxidase are similar to the corresponding shifts induced by complex formation with resting-state cytochrome c peroxidase, found previously. As with the resting-state enzyme, the complex between yeast cytochrome c and cytochrome c peroxidase-cyanide exhibits the larger set of complex-induced shifts. Two-dimensional proton NMR spectroscopy has been used to make resonance assignments. This was necessitated due to the extensive resonance overlap between the two proteins in the hyperfine shift region, since both heme proteins in this complex are low-spin paramagnetic species. These results expand preliminary work that revealed for the first time that cytochrome c binding affected the resonances of protons in the peroxidase heme pocket [Yi, Q., Erman, J. E., & Satterlee, J. D. (1992) J. Am. Chem. Soc. 114, 7907-7909]. The pattern of cytochrome c peroxidase complex-induced shifts is largely consistent with the X-ray crystal structures of these two complexes that have recently been published. PMID- 8218165 TI - Context dependence of protein secondary structure formation: the three dimensional structure and stability of a hybrid between chymotrypsin inhibitor 2 and helix E from subtilisin Carlsberg. AB - The loop region of chymotrypsin inhibitor 2 from barley has been employed as a scaffold for testing the intrinsic propensity of a peptide fragment to form a secondary structure. The helix formation of the nine amino acid residue segment Lys-Gln-Ala-Val-Asp-Asn-Ala-Tyr-Ala of helix E from subtilisin Carlsberg has been studied by the construction of a hybrid consisting of chymotrypsin inhibitor 2 (CI2) where part of the active loop has been replaced by the nonapeptide. An expression system for a truncated form of CI2 where the 19 structureless residues of the N-terminus have been removed and Leu20 replaced by methionyl was constructed from the entire 83-residue wild-type CI2 gene by polymerase chain reaction methodology. The gene encoding the hybrid was constructed from the truncated inhibitor gene. The stability of the truncated inhibitor and of the hybrid toward guanidinium chloride denaturation was examined. From these measurements, the energy of unfolding in pure water was extrapolated to 30.5 +/- 1.0 kJ/mol for the truncated inhibitor and 10.9 +/- 0.3 kJ/mol for the hybrid. These energies show that the stability of CI2 is unaffected by the N-terminal truncation but severely decreased by the loop mutations. The three-dimensional structure of the hybrid protein has been determined in solution by nuclear magnetic resonance spectroscopy using 893 distance restraints and 84 torsional angle restraints. The average root-mean-square deviation (rmsd) of 15 structures compared to their geometrical average was 0.8 +/- 0.2 A for heavy backbone atoms and 1.3 +/- 0.2 A for all heavy atoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218166 TI - Intestinal fatty acid binding protein: characterization of mutant proteins containing inserted cysteine residues. AB - Site-directed mutagenesis was used to introduce cysteine residues into the rat intestinal fatty acid binding protein, an almost all beta-sheet protein that in the wild-type contains neither cysteine nor proline residues. Six mutants (I23C, S53C, V60C, L72C, L89C, and A104C) with a single cysteine residue substituted for a hydrophobic residue were characterized by their stability toward denaturants at pH 7.2 and 9.6, by their fluorescent properties, and by their reactivity toward the sulfhydryl modifying reagents 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and 4,4'-dipyridyl disulfide (4-PDS). In terms of protein stability, the substitutions were reasonably conservative with only two (V60C and L89C) being somewhat less stable than the wild-type. The mutant proteins differed considerably, however, in their reactivity toward the modifying reagents. One residue, Cys89, located in a hydrophobic core near a turn between two beta strands, was unreactive, while two residues, Cys60 and Cys104, located in the middle of beta-strands in the cavity into which fatty acid binds, reacted only very slowly and were further protected by oleate. Cys53, located near a turn and partially buried, appeared to have an unusually low pK value. Two residues, Cys23 and Cys72, reacted more rapidly in the native protein than in the unfolded protein. Both residues are located near the portal for the fatty acid binding, and one, Cys72, was strongly protected from modification by the presence of oleate. Examination of the crystal structure indicates that Cys72 is not easily solvent-accessible. We conclude that this high reactivity for this residue may be a consequence of rapid conformational flexibility in this region of the structure. PMID- 8218167 TI - Hydrogen exchange in unligated and ligated staphylococcal nuclease. AB - The exchange kinetics of over 70% of the 143 backbone amide hydrogens in staphylococcal nuclease H124L (nuclease H124L), both in its unligated state and in its ternary complex with Ca2+ and thymidine 3',5'-bisphosphate, have been quantified by nitrogen-15 resolved proton nuclear magnetic resonance spectroscopy. Protection factors for the slowly exchanging hydrogens in unligated nuclease H124L at 37 degrees C and pH 5.5 were found to vary by over one order of magnitude. This range of protection factors has been interpreted in the framework of global and local structural fluctuations. The three most highly protected hydrogens (K24, L25, M26) map to strand 2 of the central five-stranded beta barrel. The free energy change for the opening reaction which exposes these hydrogens to the solvent (delta G(degree)op) was calculated from the exchange rates in the native and denatured states, the latter values being estimated from model peptide exchange studies [Molday, R. S., Englander, S. W., & Kallen, R. G. (1972) Biochemistry 11, 150-158]. Close agreement was found between delta G(degree)op and delta G(degree)u, the free energy change of unfolding as measured by urea denaturation experiments. Exchange of these hydrogens thus appears to occur via global unfolding of the protein. One region exhibited somewhat lower protection factors: it mapped to the C-terminal portions of helix 2 and helix 3 and to part of the intervening segment. This region has been identified as a minor hydrophobic domain of nuclease [Shortle, D., Stites, W. E., & Meeker, A. K. (1990) Biochemistry 29, 8033-8041].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218168 TI - Chemical probing of tDNAPhe with transition metal complexes: a structural comparison of RNA and DNA. AB - The three-dimensional folding of tDNAPhe has been examined and compared to native tRNAPhe using a series of shape-selective transition metal complexes as chemical probes of nucleic acid structure. Rh(phen)2 phi 3+ (phen = phenanthroline, phi = 9,10-phenanthrenequinonediimine), which targets sites of tertiary interaction in tRNAPhe, cleaves specifically at similar sites on tDNAPhe. However, this rhodium complex also targets 5'-pyr-pyr-pur-3' sites within the acceptor and anticodon stems of tDNA;Rh(phen)2 phi 3+ generally targets 5'-pyr-pyr-pur-3' sites in B form duplex DNA. On tRNAPhe, Rh(DIP)3(3+) (DIP = 4,7-diphenyl-1,10 phenanthroline) specifically cleaves C70, which neighbors a GU mismatch, and targets psi 55 as well, within the hydrophobic region of tRNAPhe. On tDNAPhe no specific cleavage by Rh(DIP)3(3+) is observed. The cleavage studies, taken together, indicate that globally the tertiary folding of tDNAPhe resembles that of tRNAPhe. However, the double helical regions of the DNA analog differ from tRNAPhe, likely in adopting a more B-like conformation. As a consequence, the GT mismatch within the acceptor stem of tDNA does not present the same recognition elements as in tRNA, and the GT mismatch is no longer recognized by the shape selective rhodium complex. The present work underscores the utility of applying DNA analogs to studies of RNA structure and function, since the general folding characteristics of the two polymers are likely to be similar. However, structural probing with transition metal complexes offers a valuable companion to such experiments, since the shape-selective probes, with sensitivity, may be used to delineate locally on the polymer those regions which may differ in structure. PMID- 8218169 TI - Identification of substrate-analog trypsin inhibitors through the screening of synthetic peptide combinatorial libraries. AB - Synthetic peptide combinatorial libraries (SPCLs), which are made up in total of tens to hundreds of millions of peptides, enable the systematic screening for biologically active peptides in virtually all in vitro and even in vivo assay systems. In the current study, the applicability of this method to the identification of peptide enzyme inhibitors was investigated using trypsin as the model enzyme. A specifically designed library of hexapeptide mixtures was synthesized on cotton carriers and screened. The synthetic approach, using cotton as a solid support, was modified so that the deprotected peptides remained attached to the cotton carrier until they were released into solution directly prior to being assayed. Following an iterative process of synthesis and screening, in which all of the positions of the sequence were successively defined, a number of individual hexapeptides with trypsin inhibitory activity were identified. The most active, defined individual peptide sequence was then reincorporated into a new library, now made up of dodecapeptide mixtures. The iterative screening and synthesis of this library led to a dodecapeptide with improved inhibitory activity when compared to the hexapeptide from which it was derived. PMID- 8218170 TI - Cell-specific physical and functional coupling of human 5-HT1A receptors to inhibitory G protein alpha-subunits and lack of coupling to Gs alpha. AB - We have studied the physical and functional linkages of heterologously expressed human 5-HT1A receptors to G protein alpha-subunits in HeLa and CHO-K1 cells. HeLa cells expressed immunoreactivity to G(i) proteins with an apparent rank order of G(i) alpha 3 (approximately 1 pmol/mg of protein) >> G(i) alpha 1 (approximately 0.1 pmol/mg) >> G(i) alpha 2 (< 0.02 pmol/mg), whereas CHO-K1 cells expressed immunoreactivity to G(i) alpha 2 (approximately 5 pmol/mg) >> G(i) alpha 3 (approximately 0.7 pmol/mg), but not to G(i) alpha 1. Both cell lines expressed large and small forms of Gs alpha, but neither expressed detectable G(o) alpha. Agonist-promotable physical coupling of the 5-HT1A receptor to G proteins was examined with high-affinity agonist binding and with co-immunoprecipitation using rabbit anti-receptor IgG fractions. Agonist treatment induced coupling of the 5 HT1A receptors to G proteins with an apparent rank order of G(i) alpha 3 > G(i) alpha 1, G(i) alpha 2 in HeLa cells and G(i) alpha 3 > G(i) alpha 2 in CHO-K1 cells. Agonist-promotable functional coupling of the 5-HT1A receptors to inhibition of adenylylcyclase was measured in membranes derived from HeLa and CHO K1 cells expressing approximately 2.5-3 pmol of receptors/mg of protein by preincubation with antisera raised against the carboxyl termini of the G(i) protein alpha-subunits. A noteworthy difference between the two cell types was that antisera against the predominant G protein (G(i) alpha 2) were substantially more efficacious than G(i) alpha 3 antisera at blocking functional coupling to adenylylcyclase inhibition in CHO-K1 cells, whereas in HeLa cells, antisera against nonpredominant G proteins (G(i) alpha 1/G(i) alpha 2) were equally as effective as those against the predominant G protein (G(i) alpha 3). No physical or functional coupling of the 5-HT1A receptor to Gs alpha isoforms was detected in either cell line. These findings suggest that the 5-HT1A receptor can physically couple to multiple distinct G(i) proteins in mammalian cell membranes and that functional coupling to adenylylcyclase inhibition may be mediated by G(i) alpha 1, G(i) alpha 2, and G(i) alpha 3. One factor influencing the relative importance of those G proteins for 5-HT1A receptor-inhibited adenylylcyclase activity appears to be their-relative levels of expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218171 TI - Movement of fatty acids, fatty acid analogues, and bile acids across phospholipid bilayers. AB - How lipophilic acids move across membranes, either model or biological, is the subject of controversy. We describe experiments which better define the mechanism and rates in protein-free phospholipid bilayers. The transbilayer movement of lipophilic acids [fatty acids (FA), covalently-labeled FA, bile acids, and retinoic acid] was monitored by entrapping pyranin, a water-soluble, pH-sensitive fluorescent molecule to measure pH inside unilamellar vesicles [Kamp, F., & Hamilton, J.A. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 11367-11370]. Equations for the pseudo-unimolecular rate constants for transbilayer movement of un ionized (kappa FAH) and ionized (kappa FA-) acids are derived. All FA studied (octanoic, lauric, myristic, palmitic, stearic, oleic, elaidic, linoleic, linolelaidic, and arachidonic) and retinoic acid exhibited rapid transbilayer movement (t 1/2 < 1 s) via the un-ionized form across small unilamellar egg phosphatidylcholine (PC) vesicles. FA produced by phospholipase A2 in the outer leaflet of PC vesicles equilibrated rapidly to the inner leaflet. Ionized FA showed enhanced transbilayer movement (kappa FA- = 0.029 s-1) in the presence of equimolar valinomycin. The three FA analogues [12-(9-anthroyloxy)stearic acid, 5 doxylstearic acid, and 1-pyrenenonanoic acid] moved across PC bilayers via the un ionized form; except for the anthroyloxy FA (kappa FAH = 4.8 x 10(-3) s-1), the rates were too fast to measure (t 1/2 < 1 s). The rate for cholic acid (CA) transbilayer movement was slow (kappa CAH = 0.056 s-1) compared to that of the more hydrophobic bile acids, deoxy- and chenodeoxycholic acid (t 1/2 < 1 s). The taurine conjugates of the three bile acids did not cross the bilayer (t 1/2 > 1 h). A further application of the pyranin method was to measure the partitioning of FA and bile acids among water, albumin, and PC vesicles. Our results show that the ability of lipophilic acids to permeate a PC bilayer rapidly is dependent on the presence of the un-ionized acid in the membrane interface. Considering the fast unfacilitated movement of FA across protein-free phospholipid bilayers, it is unlikely that there is a universal need for a transport protein to enhance movement of FA across membrane bilayers. Physiological implications of proton movement accompanying fast movement of un-ionized lipophilic acids (and the consequent generation of a pH gradient) are discussed. PMID- 8218172 TI - Site-specific N-glycosylation and oligosaccharide structures of recombinant HIV-1 gp120 derived from a baculovirus expression system. AB - We report the complete structures of the N-linked oligosaccharides and the site specificity of the N-glycosylation of recombinant gp120 (rgp120) of the HIV-1 BH8 isolate produce by a baculovirus expression system. Glycopeptides derived from the tryptic digests of intact rgp120 or of cyanogen bromide-generated fragments of rgp120 were isolated by their binding to concanavalin A-Sepharose and were purified by reversed-phase HPLC. The isolated glycopeptides were treated with PNGase F, releasing the carbohydrate moiety while converting Asn to Asp, and identified by amino acid analysis and/or peptide sequencing. Our results indicate that all 22 potential N-glycosylation sites in the rgp120 sequence are utilized. We did not detect N-acetylgalactosamine in rgp120, indicating that the glycoprotein lacks typical O-linked oligosaccharides. To investigate the oligosaccharide structures at the sites of glycosylation, we determined the carbohydrate composition for each site and characterized the oligosaccharides by 1H-NMR spectroscopy and by oligosaccharide mapping using high pH anion-exchange chromatography. Mannose and N-acetylglucosamine were the only sugars observed in the intact rgp120 and likewise in individual glycopeptides. All glycopeptides derived from rgp120 contained high mannose-type N-linked oligosaccharides, ranging from GlcNAc2Man5 to GlcNAc2Man9. However, different glycosylation sites showed varied degrees of processing of the high mannose-type oligosaccharides, as characterized by the ratio of GlcNAc2Man8-9 to GlcNAc2Man5-7. These results demonstrate that N-glycosylation of rgp120 in the baculovirus expression system occurs at all potential sites and is site specific in terms of oligosaccharide structures. PMID- 8218173 TI - In vitro functional characterization of overproduced Escherichia coli katF/rpoS gene product. AB - The katF/rpoS gene product (sigma s), a central regulator of stationary-phase gene expression in Escherichia coli, has been purified from an overproducing strain. sigma s was used as an immunogen for the production of monoclonal antibodies. Previous sequence analysis of sigma s strongly indicated homology to the sigma factor family. We show biochemically in this paper that sigma s is a sigma factor. This protein can bind to core RNA polymerase (E), and this binding can be competed effectively by the major E. coli transcription initiation factor, sigma 70. Immunopurified sigma s holoenzyme (E sigma s) transcribes the promoters of the bolAp1 gene and the xthA gene. Interestingly, both promoters can also be transcribed by sigma 70 holoenzyme (E sigma 70). PMID- 8218174 TI - NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase is the mammalian homolog of the mitochondrial enzyme encoded by the yeast MIS1 gene. AB - The recombinant human bifunctional NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase is unique in its absolute requirement for Mg2+ and inorganic phosphate. Both ions affect the affinity of the enzyme for NAD and have no effect on the binding of methylenetetrahydrofolate. The NAD cofactor can be replaced by NADP with a much higher KM and lower VMAX. Kinetic investigation using NADP supports the role of Mg2+ in dinucleotide binding and illustrates that the 2'-phosphate can substitute for phosphate in this process. The human NAD-dependent bifunctional enzyme has a 44% amino acid sequence identity with the dehydrogenase-cyclohydrolase domain of the yeast mitochondrial NADP-dependent trifunctional enzyme encoded by the MIS1 gene, compared to 37% identity with the corresponding domain of the cytosolic trifunctional enzyme. The sequence comparison and the kinetic properties suggest that the NAD bifunctional enzyme is the mammalian homolog of the yeast mitochondrial trifunctional enzyme, which has evolved a unique use of inorganic phosphate to change its dinucleotide specificity from NADP to NAD. Its role is proposed to be in providing formyltetrahydrofolate for the synthesis of formylmethionyl transfer RNA required for the initiation of protein synthesis in mitochondria. PMID- 8218175 TI - Metabolite-modulated complex formation between alpha-glycerophosphate dehydrogenase and lactate dehydrogenase. AB - A modified Hummel-Dreyer equilibrium chromatography technique was used to test the hypothesis that NADH induces the molecular association of lactate dehydrogenase (LDH) and alpha-glycerol-3-phosphate dehydrogenase (alpha-GDH). In the presence of a very limited NADH concentration, a unique elution profile with a new peak running immediately ahead of a trough at the free alpha-GDH elution position is obtained. The appearance of this peak-trough profile is physical evidence that reversible association between LDH and alpha-GDH occurs over a very limited range of free NADH concentrations. The association constant for this complex formation between LDH and alpha-GDH is estimated to be 2.0 microM-1. With the NADH concentration increased to saturation level, no evidence of binding is observed. Such concentration-dependent behavior suggests that the strong competition between LDH and alpha-GDH for the limited amount of NADH tends to promote the enzyme-enzyme contact in order to make the most efficient use of the shared metabolite. The experimental results described in this article make a convincing argument for a metabolite-modulated enzyme-enzyme interaction along this metabolic pathway. PMID- 8218176 TI - Mutation of monofunctional 6-phosphofructo-2-kinase in yeast to bifunctional 6 phosphofructo-2-kinase/fructose 2,6-bisphosphatase. AB - We have shown previously that 6-phosphofructo-2-kinase in yeast has negligible fructose-2,6-bisphosphatase activity even though resembling in part of its C terminal sequence the phosphatase domain of the bifunctional liver enzyme. Here we show that exchanging Ser-404 to His-404 in the yeast peptide creates a bifunctional enzyme with a fructose-2,6-bisphosphatase activity involving a phosphoprotein intermediate. Like mammalian bifunctional enzymes, the His-404 mutant protein is readily phosphorylated by fructose 2,6-P2 with a half saturation of 0.4 microM, the same Km value as for its fructose-2,6 bisphosphatase activity. Protein phosphorylation by the C-subunit of cAMP dependent protein kinase, presumably at a C-terminal consensus site, increases the Km value to 1.5 microM. The newly created fructose-2,6-bisphosphatase is inhibited competitively by its product fructose 6-P with a K(i) of 0.6 mM. No effect of the His-404 mutation was found on 6-phosphofructo-2-kinase activity, in line with the mutant yeast enzyme having independent kinase and phosphatase domains, like its mammalian wild-type counterparts. The results would fit with the evolution of the PFK26 gene having involved fusion between kinase and phosphatase genes--as proposed for the mammalian enzyme--but with accompanying or later silencing of the fructose-2,6-bisphosphatase activity. PMID- 8218177 TI - Tetracenomycin F2 cyclase: intramolecular aldol condensation in the biosynthesis of tetracenomycin C in Streptomyces glaucescens. AB - Tetracenomycin (Tcm) F2 cyclase, which catalyzes the cyclization of the anthrone Tcm F2 to the naphthacenone Tcm F1 in the biosynthesis of the anthracycline antibiotic Tcm C in Streptomyces glaucescens, has been purified to homogeneity and characterized. The N-terminal sequence of the enzyme establishes that it is encoded by the tcmI gene, whose deduced product has a molecular weight of 12,728. SDS-PAGE analysis gave a single band with a molecular weight of 12,500, whereas gel-filtration chromatography yielded a molecular weight of 37,500, indicating that the Tcm F2 cyclase is a homotrimer in solution. Under pH > or = 8.0, the enzyme catalyzes the cyclization of Tcm F2 to Tcm F1 and has a Km of 121 +/- 18.2 microM and Vmax of 704 +/- 62.3 nmol.min-1.mg-1. In contrast, under pH < or = 6.5, it catalyzes the cyclization of Tcm F2 to 9-decarboxy Tcm F1, a known shunt metabolite of the Tcm C biosynthetic pathway. Tcm F2 cyclase represents the first discrete enzyme for carbon-carbon bond formation via an intramolecular aldol condensation-dehydration mechanism, a key biochemical operation proposed in the early steps of the biosynthesis of all aromatic polyketides. PMID- 8218178 TI - Selective disulfide formation in truncated apamin and sarafotoxin. AB - Apamin and sarafotoxin are small peptide toxins which are 18 and 21 residues long, respectively. They both have cysteines at positions 1, 3, 11, and 15. However, the non-cysteine portions of their sequences and the positions of their disulfides are different. In native apamin, the cysteines form disulfides 1-11 and 3-15, whereas in sarafotoxin they form the 1-15 and 3-11 pairs. Truncated analogs have been synthesized which lack the carboxyl-terminal tails following cysteine-15. When oxidized by glutathione, both truncated sequences retain the ability to selectively populate the disulfide combination observed in the respective full-length parent. This ability is retained in the presence of the denaturing agent 5 M guanidinium chloride. Circular dichroism spectra of the nativelike isomers are nearly identical to those of the parent sequence, and are not affected by heating to 75 degrees C or exposure to 5 M guanidinium chloride. The alpha helix observed in apamin is a consequence of both the disulfide topology and the non-cysteine portions of the sequence. There is not much alpha helix when apamin is forced to adopt the disulfides found in native sarafotoxin or when sarafotoxin is forced to adopt the disulfides found in native apamin. PMID- 8218179 TI - Electrochemical and spectral analysis of the long-range interactions between the Qo and Qi sites and the heme prosthetic groups in ubiquinol-cytochrome c oxidoreductase. AB - The results are presented of an electrochemical and high-resolution spectral analysis of the heme prosthetic groups in the bc1 complex from mouse cells. To study the long-range interactions between the Qo and Qi quinone redox sites and the b heme groups, we analyzed the effects on the proximal and distal b heme groups, and the c1 heme, of inhibitors that tightly and specifically bind to the Qi or Qo redox site. A number of results emerged from these studies. (1) There is inhomogeneous broadening of the b heme alpha band absorption spectra. Furthermore, contrary to the conclusion from low-resolution spectral analysis, the higher energy transition in the split-alpha band spectrum of the bL heme is more intense than the lower energy transition. (2) Inhibitors that bind at the Qi site have significant effects upon the electronic environment of the distal bL heme. Conversely, Qo site inhibitors induced changes in the electronic environment of the distal bH heme. (3) In contrast, inhibitor binding at either site has little effect upon the midpoint potential of the distal heme. (4) Experiments in which both a Qi and a Qo inhibitor are bound at the redox sites indicate that the long-range effects of one inhibitor are not blocked by the second inhibitor; enhanced effects are often observed. (5) In the double inhibitor titrations involving the Qo inhibitor myxothiazol, there is evidence for two electrochemically and spectrally distinct species of the bL heme group, a phenomenon not observed previously. (6) The high-resolution deconvolutions of alpha band absorption spectra allow an interpretation of these inhibitor-induced changes in terms of homogeneous broadening, inhomogeneous broadening, and changes in x-y degeneracy. The general conclusion from these experiments is that when an inhibitor binds to a quinone redox site of the cytochrome b protein, it produces local conformational changes that, in turn, are transmitted to distal regions of the protein. The ligation of the bH and bL hemes between two parallel transmembrane helices provides a mechanism by which long-distance interactions can be propagated. The lack of long-range effects upon the midpoint potentials of the heme groups suggests, however, that protein conformational changes are unlikely to be a major control mechanism for the transmembrane electron- and proton-transfer steps of the Q cycle. PMID- 8218180 TI - Site-directed mutagenesis of highly conserved residues in helix VIII of subunit I of the cytochrome bo ubiquinol oxidase from Escherichia coli: an amphipathic transmembrane helix that may be important in conveying protons to the binuclear center. AB - Cytochrome bo from Escherichia coli is a ubiquinol oxidase which is a member of the superfamily of heme-copper respiratory oxidases. This superfamily, which includes the eukaryotic cytochrome c oxidases, has in common a bimetallic center consisting of a high-spin heme component and a copper atom (CuB) which is the site where molecular oxygen is reduced to water. Subunit I, which contains all the amino acid ligands to the metal components of the binuclear center, has 15 putative transmembrane spanning helices, of which 12 are common to the entire superfamily. Transmembrane helix VIII has been noted to contain highly conserved polar residues that fall along one face of the helix. These residues could, in principle, be important components of a pathway providing a conduit for protons from the cytoplasm to gain access to the binuclear center. These conserved residues include Thr352, Thr359, and Lys362. In addition, Pro358, in the middle of this transmembrane helix, is totally conserved in the superfamily. Some substitutions for Thr352 (Ala, Asn) result in major perturbations at the binuclear center as judged by the low-temperature Fourier transform infrared (FTIR) absorbance difference spectroscopy of the CO adducts. Whereas Thr352Ala is inactive enzymatically, both Thr352Asn and Thr352Ser have substantial activity. Substitutions for Thr359 (Ala or Ser) also do not perturb the spectroscopic properties of the binuclear metal center, but the Thr359Ala mutant is devoid of enzyme activity. Changing the neighboring Pro358 to Ala has no detectable effect on the properties of the oxidase. However, all substitutions for Lys362 (Leu, Met, Gln, or Arg) are inactive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218181 TI - Quantitative structural comparisons of heme protein crystals and solutions using resonance Raman spectroscopy. AB - Resonance Raman difference spectra have been used to compare crystal and solution samples of metmyoglobin (metMb), deoxymyoglobin (deoxyMb), and cytochrome P450. At pH 6.0, the frequency shifts of the heme core size sensitive bands v2, v3, and v4 were determined to be less than 0.3, 1.0, and 0.3 cm-1, respectively, for metMb and to be less than 1.0, 1.0, and 0.3 cm-1, respectively, for deoxyMb. This shows that the heme core size differences between the crystal and solution conformations are less than 0.002 A for metMb and less than 0.003 A for deoxyMb. These results disagree with a recent extended X-ray absorption fine structure study [Zhang, K., Chance, B., Reddy, K. S., Ayene, I., Stern, E. A., & Bunker, G. (1991) Biochemistry 30, 9116-9120] which claims that a 0.05-A difference exists in the average iron-ligand distance between the crystalline and solution forms of metMb at pH 6.5. At pH 8.5, metMb solution samples change gradually from a predominantly high-spin to a predominantly low-spin species as the ammonium sulfate concentration is increased to the level found in the crystal mother liquor. No Raman frequency shifts are found between the crystal and solution forms of metMb at pH 8.5 when the ammonium sulfate concentrations are equal. On the other hand, for deoxyMb, we find a significant alteration in the 220/240-cm-1 line shape and relative intensities, suggesting that some histidine-heme perturbation takes place upon crystallization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218182 TI - Alternative pathways and reactions of benzyl alcohol and benzaldehyde with horse liver alcohol dehydrogenase. AB - Liver alcohol dehydrogenase catalyzes the reaction of NAD+ and benzyl alcohol to form NADH and benzaldehyde by a predominantly ordered reaction. However, enzyme alcohol binary and abortive ternary complexes form at high concentrations of benzyl alcohol, and benzaldehyde is slowly oxidized to benzoic acid. Steady-state and transient kinetic studies, equilibrium spectrophotometric measurements, product analysis, and kinetic simulations provide estimates of rate constants for a complete mechanism with the following reactions: (1) E<-->E-NAD+<-->E-NAD(+) RCH2OH<-->E-NADH-RCHO<-->E-NADH<-->E ; (2) E-NADH<-->E-NADH-RCH2OH<-->E-RCH2OH<- >E; (3) E-NAD+<-->E-NAD(+)-RCHO-->E- NADH-RCOOH<-->E-NADH. The internal equilibrium constant for hydrogen transfer determined at 30 degrees C and pH 7 is about 5:1 in favor of E-NAD(+)-RCH2OH and has a complex pH dependence. Benzyl alcohol binds weakly to free enzyme (Kd = 7 mM) and significantly decreases the rates of binding of NAD+ and NADH. The reaction of NAD+ and benzyl alcohol is therefore kinetically ordered, not random. High concentrations of benzyl alcohol (> 1 mM) inhibit turnover by formation of the abortive E-NADH-RCH2-OH complex, which dissociates at 0.3 s-1 as compared to 6.3 s-1 for E-NADH. The oxidation of benzaldehyde by E-NAD+ (Km = 15 mM, V/E = 0.4 s-1) is inefficient relative to the oxidation of benzyl alcohol (Km = 28 microM, V/E = 3.1 s-1) and leads to a dismutation (2RCHO-->RCH2OH + RCOOH) as E-NADH reduces benzaldehyde. The results provide a description of final product distributions for the alternative reactions catalyzed by the multifunctional enzyme. PMID- 8218183 TI - The refolding of cis- and trans-peptidylprolyl isomers of barstar. AB - Barstar, a small globular protein which undergoes reversible unfolding, is a good candidate for studies on protein folding. It possesses two cysteine residues that complicate folding studies by forming a variable mixture of disulfide-bridged forms. We have constructed and analyzed, therefore, a double mutant Cys40- >Ala,Cys82-->Ala. Equilibrium unfolding with urea follows a simple two-step mechanism. The midpoint for unfolding ([U]1/2) is 3.87 +/- 0.03 M urea, with m(delta delta G/delta [urea]) = 1.25 +/- 0.04 kcal/mol2. The free energy of unfolding, delta GU-FH2O, is 4.84 +/- 0.18 kcal/mol. Identical results were found on monitoring the intrinsic tryptophan fluorescence or the circular dichroism signal at 221 nm, showing that the transition is due to the global denaturation of the protein. Barstar contains two proline residues, one of which (Pro48) has a cis N-aminoacyl bond conformation in the folded state. A transiently generated form of the unfolded protein, which contains the proline residues in their native conformations, has a rate constant for refolding (31 s-1) similar to that for refolding of the equilibrium-unfolded protein, which results in a "misfolded" form of the protein (32 s-1). The two refolded states are different: the free energies of unfolding measured from kinetic constants for the native and misfolded variants are 5.4 +/- 0.3 and 2.85 +/- 0.1 kcal/mol, respectively. The rate constant for the unfolding in water of the misfolded protein is 0.87 s-1, compared with 0.068 s-1 for the unfolding of the native protein. This difference can be explained by a nonnative trans peptidyl-proline bond at position 48 in the misfolded protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218184 TI - Characterization of isomers of monoamminechromium-ATP and their use in mapping enzyme active sites. AB - Twelve isomers formed by the reaction of monoamminechromium(III) with ATP have been synthesized. Isomerism in this system results from chirality around the beta phosphorus of the ATP, the position of the ammonia ligand, the relative orientation of the ammonia and the AMP, and the presence of ring-puckering conformers. By using chromatography on cross-linked cycloheptaamylose, reverse phase C-18 HPLC, and cation-exchange FPLC, these isomers have been separated and purified. Their structures have been identified by (1) cleavage by periodate, followed by elimination in the presence of diethylenetriamine and subsequent phosphate insertion to give lambda, delta, or meso facial monoamminechromium tripolyphosphate with molar ellipticities of +240, -240, or 0 deg cm2 dmol-1 at 550 nm, respectively, (2) cleavage by nucleotide pyrophosphatase to give meridional or facial monoamminechromium pyrophosphate, (3) spectral data, and (4) rates of interconversion of isomers. All possible isomers are seen except those with ammonia syn to AMP. Since the substitution of ammonia for water in the inner coordination sphere appears to diminish affinity for enzymes when the ammonia is in contact with the protein but not when it faces the solvent, these isomers are useful for mapping of enzyme active sites. Their use as probes of enzyme structure is illustrated by their behavior with yeast hexokinase. PMID- 8218185 TI - Role of a conserved histidine residue, His-195, in the activities of the Escherichia coli mannitol permease. AB - The mannitol permease, an enzyme II of the phosphoenolpyruvate-dependent carbohydrate phosphotransferase system (PTS) of Escherichia coli, carries out the transport and phosphorylation of D-mannitol in this organism. Previous studies have shown that His-554 and Cys-384 in the mannitol permease are sequentially phosphorylated in reactions necessary for the transport and phosphorylation of the substrate. These residues are located in a large cytoplasmic domain of the protein. Interaction of the permease with mannitol, and its membrane translocation, however, must involve the N-terminal, transmembrane domain (EIIC domain) of the protein. In this report, we use site-directed mutagenesis and mutant complementation to investigate the role of His-195 in the EIIC domain of the mannitol permease, a residue that is conserved in many PTS permeases. In a previous report [Weng, Q.-P., Elder, J., & Jacobson, G. R. (1992) J. Biol. Chem. 267, 19529-19535], we inferred a role for His-195 that involves its hydrogen bonding ability. Here we show that His-195 plays a role in high-affinity mannitol binding. Moreover, mutant complementation studies show that a functional His-195 must be on the same subunit as a functional Cys-384 in a permease dimer for phosphotransfer to mannitol to occur. These results and kinetic studies of His 195 mutant proteins imply that His-195 also may play an important role in this phosphotransfer reaction. His-195 is predicted to be in a cytoplasmic "loop" in the EIIC domain of the mannitol permease, in which several other residues have been shown to have roles in mannitol permease activity. PMID- 8218186 TI - Calcium-dependent regulation of the caldesmon-heavy meromyosin interaction by caltropin. AB - The binding of chicken gizzard caldesmon to smooth muscle heavy meromyosin (HMM) was studied using caldesmon-Sepharose 4B affinity chromatography, far-ultraviolet circular dichroism (CD), and the fluorescent probe acrylodan. When HMM was applied to a caldesmon-Sepharose column in the presence of 40 mM NaCl, most of the protein was retained on the column, and HMM could be eluted by increasing the NaCl level to 0.5 M; this interaction was not Ca(2+)-dependent. Far-UV CD studies indicated an interaction between caldesmon and HMM since the experimentally observed ellipticity values at 222 and 207 nm deviated from the theoretical values for the complex, and this interaction was also not Ca(2+)-sensitive. Addition of HMM to a caldesmon-caltropin complex induced a conformational change suggesting the formation of a ternary complex for which Ca2+ was essential. Acrylodan-labeled caldesmon, when excited at 375 nm, had an emission maximum at 515 +/- 2 nm. Addition of HMM resulted in a nearly 20% decrease in fluorescence intensity with little or no shift in the emission maximum. Titration of HMM with labeled caldesmon indicated a strong affinity for HMM [K(a) was on the order of (4.5 +/- 0.5) x 10(7) M-1], and this interaction was observed both in the presence and in the absence of calcium. When HMM was titrated with labeled caldesmon in the presence of caltropin in a 0.2 mM Ca2+ medium, its affinity for caldesmon was lowered nearly 3-fold [K(a) approximately (1.50 +/- 0.5) x 10(7) M 1].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218187 TI - Cross-linking of Escherichia coli RNA polymerase subunits: identification of beta' as the binding site of omega. AB - The omega protein is a peptide found in near-stoichiometric levels in highly purified Escherichia coli RNA polymerase. In order to determine the binding site of omega to RNA polymerase, we cross-linked omega to RNA polymerase with the hetero-bifunctional cross-linker N-hydroxysuccinimidyl 4-azidobenzoate and analyzed for cross-linked partners using antibodies raised against each of the subunits. Our analysis indicates that omega cross-links predominantly with the beta' subunit, while a very low level of cross-linking was detected to the alpha subunit. We did not detect cross-linking to either the sigma 70 or the beta subunits. This report demonstrates the utility of combining cross-linking and immunological techniques to determine interactions between RNA polymerase subunits. PMID- 8218188 TI - NMR structural studies on a nonnatural deoxyribonucleoside which mediates recognition of GC base pairs in pyrimidine-purine-pyrimidine DNA triplexes. AB - As a part of our ongoing efforts to define the structural aspects of unusual pairing alignments in DNA triplexes by nuclear magnetic resonance spectroscopy, we have examined the structural role of a nonnatural deoxyribonucleoside, P1, that has been shown to mediate the recognition of GC base pairs in pyrimidine purine-pyrimidine DNA triplexes [Koh, J.S., & Dervan, P.B. (1992) J. Am. Chem Soc. 114, 1470]. A qualitative interpretation of the NMR data indicates that this analog of protonated cytosine is readily accommodated in the third strand segment of an intramolecular triplex system. Furthermore, the observed NOE patterns position the imino and amino protons of P1 opposite the N7 and O6 atoms of guanine, respectively, consistent with the previously proposed pairing scheme. PMID- 8218189 TI - Energetics of arginine-4 substitution mutants in the N-terminal cooperativity domain of T4 gene 32 protein. AB - Gene 32 protein (gp32) from bacteriophage T4 is a sequence-nonspecific single strand (ss) nucleic acid binding protein which binds highly cooperatively to ss nucleic acids. The N-terminal "B" or basic domain (residues 1-21) is known to be required for highly cooperative binding by gp32 (where K(app) = K(int) omega, omega > or = 500), since its removal results in a protein which binds ss nucleic acids noncooperatively (omega = 1). In this paper, we probe the molecular details of cooperative binding by gp32 by physicochemical characterization of a set of four single amino acid substitution mutants of Arg4: Lys4 (R4K gp32), Gln4 (R4Q gp32), Thr4 (R4T gp32), and Gly4 (R4G gp32). The qualitative ranking of binding affinities to poly(A) is wild-type > or = R4K > R4Q > R4T > R4G > gp32-B (gp32 lacking the first 21 amino acids). The occluded site size is n(app) = 7.5 +/- 0.5 for all gp32s. Resolution of K(int) and omega for wild-type, R4K, R4Q, and R4T gp32s was estimated under conditions of low lattice saturation (v < or = 0.011) using multiple reverse fluorescence titrations collected at 10 mM Tris-HCl, pH 8.1, 20 degrees C, and a NaCl concentration where K(app) was (2-4) x 10(6) M-1 for each gp32 on the ribohomopolymer poly(A). Binding parameters for all gp32s were obtained directly or compared by conservative extrapolation of the [NaCl] dependence of K(app) to 0.20 M NaCl, 20 degrees C, pH 8.1. The magnitude of omega was then assumed not to vary with [NaCl] (shown for R4T gp32), allowing estimation of K(int) at 0.20 M NaCl. We find that R4K gp32 binds to poly(A) with an overall affinity (K(app)) which is 2-3-fold lower than wild-type gp32, while omega for each molecule seems indistinguishable (wild-type gp32, omega approximately 800-1300; R4K gp32, omega approximately 600-1200). Surprisingly, R4Q gp32 is characterized by an omega also not readily distinguishable from the wild-type and R4K proteins (omega approximately 800-4400), while K(app) is reduced about 10-fold. This mutant also shows a significantly reduced [NaCl] dependence of the binding to poly(A). R4T gp32 binds about 10-fold weaker than the Q mutant. It exhibits an omega ranging from 300 to 700 and a substantially reduced [NaCl] dependence (delta log K(int)/delta log [NaCl] = -1.4 from 0.10 to 0.20 M NaCl), indicative of significant perturbations in both K(int) and omega terms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8218190 TI - Influence of 5'-nearest neighbors on the insertion kinetics of the fluorescent nucleotide analog 2-aminopurine by Klenow fragment. AB - The effects of nearest neighbor interactions between a nucleotide base at the primer 3'-terminus and an incoming deoxyribonucleoside triphosphate on DNA polymerase catalyzed insertion were examined. Kinetics of inserting the fluorescent nucleotide analog 2-aminopurine deoxyribonucleotide (dAPMP) and dAMP opposite a template T by 3'-->5' exonuclease-deficient mutants of Klenow fragment (KF-) were measured on primer/templates of identical sequence except for the base pair at the 3'-primer terminus. In addition to its fluorescence properties, 2 aminopurine (AP) is an attractive probe because it is misinserted opposite T by polymerases at much higher frequencies than natural nucleotides. Misinsertion frequencies for AP are on the same order of magnitude as variations in misinsertion frequencies due to changes in local DNA sequence, which makes the statistical significance of these variations easier to document. We have established that changes in the fluorescence of AP can be used to follow the insertion of dAPMP on both steady-state and pre-steady-state time scales. Rates of insertion of dAPMP measured by fluorescence and by a polyacrylamide gel assay were similar and are sensitive to the identity of the base at the 3'-primer twice as fast as insertion following a primer terminus T. The difference in rates arises primarily from differences in kcat values, which were fastest next to G and slowest next to T, while apparent Km values were similar next to each of the 4 different nearest neighbors. The gel assay was used to measure AP misinsertion efficiencies by two methods: (1) by having dAPTP and dATP directly compete for insertion opposite T in the same reaction and (2) by measuring Vmax/Km values for each substrate in separate reactions. The results from the direct competition and separate kinetics measurements are similar. The misinsertion efficiency of dAPMP relative to dAMP opposite a template T was significantly higher next to a 3' primer terminus G (f(ins) = 0.31 +/- 0.06) than next to T (f(ins) = 0.15 +/- 0.03) for the KF- single mutant (D42A). The corresponding misinsertion efficiencies next to a 3'-primer terminus G and T were 0.20 +/- 0.02 and 0.16, respectively, for the KF- double mutant (D355A, E357A). Relative rates of insertion of dAPMP and dAMP correlate with melting temperatures calculated for nearest neighbor doublets which reflect the relative base-stacking energies. In addition to changes in insertion kinetics, polymerase-DNA dissociation rates varied with the identity of the 3'-primer terminus, differing by as much as 7-20 fold depending on the polymerase and the primer/template. PMID- 8218191 TI - Effect of cavity-creating mutations in the hydrophobic core of chymotrypsin inhibitor 2. AB - Hydrophobic residues in the core of a truncated form of chymotrypsin inhibitor 2 (CI2) have been mutated in order to measure their contribution to the stability of the protein. The free energy of unfolding of wild-type and mutants was measured by both guanidinium chloride-induced denaturation and differential scanning calorimetry. The two methods give results for the changes in free energy on mutation that agree to within 1% or 2%. The average change in the free energy of unfolding (+/- standard deviation) for an Ile-->Val mutation is 1.2 +/- 0.1 kcal mol-1, for a Val-->Ala mutation 3.4 +/- 1.5 kcal mol-1, and for either an Ile-->Ala or a Leu-->Ala mutation 3.6 +/- 0.6 kcal mol-1. This gives an average change in the free energy of unfolding for deleting one methylene group of 1.3 +/ 0.5 kcal mol-1. Two significant correlations were found between the change in the free energy of unfolding between wild-type and mutant, delta delta GU-F, and the environment of the mutated residue in the protein. The first is between delta delta GU-F and the difference in side-chain solvent-accessible area buried between wild-type and mutant (correlation coefficient = 0.81, 10 points). The second and slightly better correlation was found between delta delta GU-F and N, the number of methyl/methylene groups within a 6-A radius of the hydrophobic group deleted (correlation coefficient = 0.84, 10 points). The latter correlation is very similar to that found previously for barnase, suggesting that this relationship is general and applies to the hydrophobic cores of other globular proteins. The combined data for C12 and barnase clearly show a better correlation with N (correlation coefficient = 0.87, 30 points) than with the change in the solvent-accessible surface area (correlation coefficient = 0.82, 30 points). This indicates that the packing density around a particular residue is important in determining the contribution the residue makes to protein stability. In one case, Ile-->Val76, a mutation which deletes the C delta 1 methyl group of a buried side chain, a surprising result was obtained. This mutant was found to be more stable than wild-type by 0.2 +/- 0.1 kcal mol-1. We have solved and analyzed the crystal structure of this mutant and find that there are small movements of side chains in the core, the largest of which, 0.7 A, is a movement of the side chain that has been mutated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8218192 TI - Structure of the hydrophobic core in the transition state for folding of chymotrypsin inhibitor 2: a critical test of the protein engineering method of analysis. AB - Chymotrypsin inhibitor 2 (CI2) unfolds and refolds according to a simple two state kinetic mechanism. The single rate-determining transition state may thus be studied by kinetics of both unfolding and refolding. This has allowed the direct testing of some facets of the protein engineering procedure (phi-value analysis). The structure of the hydrophobic core of CI2 in the transition state was analyzed from kinetic and thermodynamic measurements of guanidinium chloride-induced unfolding of 11 mutants and of their rates of refolding. In all cases, the strengths of the interactions measured from refolding kinetics in water are in excellent agreement with those measured from unfolding kinetics in guanidinium chloride solutions and extrapolated to zero molar denaturant. Changes in the free energies of unfolding on mutation, as well as other equilibrium properties calculated from the rate constants, are also in excellent agreement with those measured directly from equilibrium studies. These data provide further evidence for application of the principle of microscopic reversibility to aspects of protein folding in the presence of denaturant and the validity of extrapolation to the absence of denaturant. The edges of the hydrophobic core of CI2 are significantly weakened in the transition state, and, in many cases, the interactions are totally lost. The center of the core remains partially intact; the interaction energy is lowered by about 50%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218193 TI - The tertiary structure of a DNA aptamer which binds to and inhibits thrombin determines activity. AB - The solution-state three-dimensional structure of the DNA aptamer d(G1G2T3T4G5G6T7G8T9G10G11T12T13G14G15) which binds to and inhibits thrombin has recently been determined by NMR methods (Wang et al., 1993). This DNA adopts a highly compact, highly symmetrical structure which consists of two tetrads of guanosine base pairs and three loops. The basic features of this three dimensional structure are preserved when the aptamer binds to thrombin. The three dimensional structure can be used as a basis for interpreting the relative activities of modified aptamers as well as for proposing a model for the aptamer thrombin complex. This investigation also provides a demonstration of a novel approach to medicinal chemistry in which a wide range of molecules are synthesized, a lead molecule is identified, and the structural information on the lead compound allows for rational design of additional compounds of potential therapeutic value. PMID- 8218194 TI - Purification and characterization of a novel metalloendopeptidase from Saccharomyces cerevisiae. AB - We previously identified an activity in the soluble fraction of the yeast Saccharomyces cerevisiae that is a candidate for catalyzing the proteolytic maturation of farnesylated-CXXX precursor polypeptides. We describe here a 1259 fold purification of this activity by chromatography on DEAE-cellulose, hydroxylapatite, phenyl-Sepharose, and Sephacryl S-200. Sodium dodecyl sulfate gel electrophoresis of this preparation demonstrated a single 68-kDa polypeptide chain. The experimentally determined N-terminal amino acid sequence was identical at all 20 positions with residues 28-47 of the deduced sequence of the S. cerevisiae YCL57w gene product. This analysis suggests that the YCL57w gene encodes this enzyme and that the initial translation product may contain a leader peptide. Its complete deduced amino acid sequence shows significant homology to a number of zinc metallopeptidases and is most closely related to rat metalloendopeptidase 24.15 (E.C. 3.4.24.15), an enzyme that preferentially cleaves after hydrophobic residues. Using the purified yeast enzyme, we show a unique cleavage site in the peptides bradykinin and beta-neoendorphin four residues from the C-terminus on the carboxyl side of a hydrophobic amino acid. The cleavage pattern for neurotensin revealed a major site three residues from the C-terminus also on the carboxyl side of a hydrophobic residue and a minor site four residues from the C-terminus of the peptide. This specificity is similar to that of rat endopeptidase 24.15 and may explain why the farnesylated peptide employed in our studies is a good substrate for the yeast enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218195 TI - Hyperglycemia induces a loss of phospholipid asymmetry in human erythrocytes. AB - Phospholipid asymmetry in biological membranes is maintained by an aminophospholipid-specific Mg(2+)-ATPase that transports PS and PE from the outer to the inner monolayer. Recent evidence indicates that a loss of phospholipid asymmetry occurs in erythrocytes from diabetic individuals, resulting in the appearance of PS in the membrane outer leaflet. We show that hyperglycemic treatment of normal erythrocytes duplicates this effect. Erythrocytes incubated for 18-24 h in the presence of glucose were assayed for PS transport and transmembrane phospholipid asymmetry. Phospholipid asymmetry in erythrocytes treated with high concentrations of glucose (> 5 mM) showed a time-dependent (t1/2 approximately 12 h) and concentration-dependent (half-maximal concentration approximately 7.5 mM) increase in the accessibility of PS and PE, and a decrease in the accessibility of SM and PC, to exogenous phospholipases. After an 18 h incubation with 20 mM glucose, 40% of the endogenous PS and PE was found in the outer monolayer concomitant with a decrease in the outer monolayer content of SM (from 80% to 50%) and PC (from 75% to 65%). These values are consistent with an almost complete transbilayer scrambling of erythrocyte phospholipids. The loss of PS asymmetry was verified using an assay based on the activation of the prothrombinase complex. The observed loss of asymmetry is not due to inhibition of PS transport or glucose-induced Ca2+ influx.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218196 TI - Interactions of all-trans-retinol and long-chain fatty acids with interphotoreceptor retinoid-binding protein. AB - Interphotoreceptor retinoid-binding protein (IRBP), a predominant protein in the interphotoreceptor matrix of the retina, has been implicated in transfer of retinoids between retinal pigment epithelium and photoreceptor cells. The interactions of IRBP with all-trans-retinol have been studied by three fluorescence-based methods and by measurements of binding of 3[H]-labeled all trans-retinol to this protein. It was found that IRBP contains two sites with similar but not identical affinities for all-trans-retinol. The dissociation constant of the all-trans-retinol-IRBP complex at the first site was 0.1 microM, which is about 10-fold lower than previously reported values. The second site had about 2.5-fold lower affinity for all-trans-retinol as compared to the first site. Long-chain fatty acids were found in this study to displace all-trans retinol from the stronger retinol-binding site on IRBP. Displacement of all-trans retinol was used to study the interactions of fatty acids with this protein. It was found that docosahexaenoic acid (DHA C22:6n-3), an essential fatty acid which plays an important role in vision, had the highest apparent affinity for the site probed on IRBP of all the fatty acids studied. PMID- 8218197 TI - Evaluation of viral membrane fusion assays. Comparison of the octadecylrhodamine dequenching assay with the pyrene excimer assay. AB - Membrane fusion, in particular the fusion of enveloped viruses, is often measured with an assay based on octadecylrhodamine (R18) fluorescence dequenching. We have studied the association of R18 with membranes and used the R18 assay to measure virus fusion in model systems and in cultured cells. The results were compared with those of an assay based on the decrease in excimer fluorescence of pyrene labeled phospholipids. For liposomes made from premixed R18 and phosphatidylcholine (PC), R18 fluorescence quenching was proportional to the concentration of the probe up to about 4 mol %. No quenching was found at very low concentrations of R18. However, various artificial and biological membranes labeled by the addition of R18 from an ethanolic solution showed significant quenching at such low R18 concentrations. Thus, some of the R18 was not randomly distributed but likely was associated with the surface of the membranes in the form of highly quenched clusters or micelles. Moreover, in influenza virus membranes, R18 appeared highly quenched at very low concentrations, indicative of the probe interacting with viral proteins. In contrast, pyrene-labeled PC incorporated in either liposomes or reconstituted viral membranes (virosomes) showed an excimer/monomer fluorescence ratio proportional to the concentration of probe. When intracellular membrane fusion was investigated with R18-labeled influenza virus or Semliki Forest virus (SFV), fluorescence dequenching was observed in the absence of fusion, most likely due to spontaneous probe exchange.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218198 TI - 2H NMR studies of the effect of pulmonary surfactant SP-C on the 1,2-dipalmitoyl sn-glycero-3-phosphocholine headgroup: a model for transbilayer peptides in surfactant and biological membranes. AB - Surfactant protein C (SP-C) was isolated from solvent extracts of porcine pulmonary surfactant by gel filtration chromatography. The surfactant protein was combined with dipalmitoylphosphatidylcholine deuterated at the alpha and beta positions of the choline headgroup (DPPC-d4) Deuterium nuclear magnetic resonance spectra were collected as a function of temperature for a series of protein concentrations. The splitting of the alpha-deuteron spectrum in the liquid crystalline phase was insensitive to temperature but decreased with increasing protein concentration. The response of headgroup conformation to protein concentration was consistent with an interaction between the lipid headgroup dipole and the net positive surface charge associated with the protein. The observed effect per charge on the alpha splitting was less than that reported for singly-charged amphiphiles [Scherer, P. G., & Seelig, J. (1989) Biochemistry 28, 7720-7728] but was similar to that obtained using a multipled-charged amphiphilic polypeptide [Roux, M., Neumann, J.-M., Hodges, R. S., Devaux, P. F., & Bloom, M. (1989) Biochemistry 28, 2313-2321]. This comparison suggests that the charges on SP-C are located near the bilayer surface. The possibility that the headgroup response is sensitive to the degree of clustering of surface charge is discussed. The beta-deuteron splitting in the liquid-crystalline phase decreased with increasing temperature but was relatively insensitive to protein concentration, suggesting that the torsion angle about the C alpha-C beta bond might be sensitive to steric interactions between the lipid headgroup and the protein. PMID- 8218199 TI - Homo- and heteronuclear two-dimensional NMR studies of the globular domain of histone H1: sequential assignment and secondary structure. AB - A recombinant 75 amino acid polypeptide corresponding to the globular domain of the chicken histone H1 (GH1) has been studied by 1H homonuclear and 1H-15N heteronuclear 2D NMR spectroscopy. Sequential assignment of the backbone and beta proton resonances has enabled us to determine the secondary structure of GH1. It was found to consist of three helical regions (T7-S17, L25-Y37, E40-K56) and probably a beta-hairpin (L59-L73). This structure is similar to the structure of the globular domain of histone H5 (GH5) obtained both by NMR spectroscopy [Zarbock et al. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 7628-7632; Clore et al. (1987) EMBO J. 6, 1833-1842] and by X-ray crystallography [Ramakrishnan et al. (1993) Nature 362, 219-223]. The beta-hairpin as suggested for GH1 is also present in the X-ray structure of GH5 but has not been reported for the NMR structure of GH5. PMID- 8218200 TI - Metal ion binding to dog osteocalcin studied by 1H NMR spectroscopy. AB - One-dimensional 1H NMR was employed to study the effects of Ca2+ and Lu3+ binding on the apo and calcium-saturated forms of dog bone Gla protein (BGP, osteocalcin). Titration of apo dog BGP with Ca2+ in 20 mM NaCl showed spectral perturbations consistent with the binding of 5 mol equiv of calcium in the NMR slow-exchange limit. The first 2 Ca2+ equiv induced significant conformational changes in the apoprotein, binding cooperatively with a Kd1 approximately 5.0 x 10(-4) M and a Hill coefficient H = 2.3 in 20 mM NaCl. The last 3 equiv bound with a slightly weaker affinity and did not induce significant structural changes. Neither the affinity nor the stoichiometry of calcium binding was significantly altered at 150 mM NaCl. The addition of only 1 Lu3+ equiv to apo dog osteocalcin was sufficient to induce the same spectral perturbations as 2 Ca2+ ions. The addition of 2 Lu3+ equiv to calcium-saturated osteocalcin had little effect on its 1H NMR spectrum, and BGP aggregated at [Lu3+]o/[BGP]o ratios greater than 2 in either the presence or absence of calcium. The spectrum of calcium-saturated osteocalcin was invariant at < or = 55 degrees C (< or = 50 degrees C in 150 mM NaCl), after which the proton resonances shifted to frequencies more characteristic of apo BGP. Saturation with calcium somewhat stabilized the apo dog osteocalcin protein against conformational changes induced at pH extremes; apo BGP was stable at 6.0 < or = pH < or = 10, and calcium saturated BGP was stable at 5.8 < or = pH < or = 10. Both our NMR and gel filtration data indicate that calcium-saturated osteocalcin exists as a dimer at both high and low protein concentrations. A conformational change in dog osteocalcin was thus induced by the cooperative association of Ca2+ to two high affinity sites on the protein and stabilized by the association of 3 additional Ca2+ equiv. The results of our temperature and calcium binding studies were consistent with an estimated Kd1 approximately 5.0 x 10(-4) M for the two high affinity sites. Lutetium induced the same structural changes in osteocalcin as calcium, but the two high-affinity Ca2+ binding sites did not have equal affinities for Lu3+. The BGP:Ca2+ complex was unstable at the low pH conditions induced by osteoclasts during bone resorption, yet the osteocalcin protein retained a BGP:Ca(2+)-like conformation at low pH. However, unlike the calcium saturated form of the protein, osteocalcin was monomeric at low pH. PMID- 8218201 TI - Energetic cost and structural consequences of burying a hydroxyl group within the core of a protein determined from Ala-->Ser and Val-->Thr substitutions in T4 lysozyme. AB - In order to determine the thermodynamic cost of introducing a polar group within the core of a protein, a series of nine Ala-->Ser and 3 Val-->Thr substitutions was constructed in T4 lysozyme. The sites were all within alpha-helices but ranged from fully solvent-exposed to totally buried. The range of destabilization incurred by the Ala-->Ser substitutions was found to be very similar to that for the Val-->Thr replacements. For the solvent-exposed and partly exposed sites the destabilization was modest (approximately less than 0.5 kcal/mol). For the completely buried sites the destabilization was larger, but variable (approximately 1-3 kcal/mol). Crystal structure determinations showed that the Ala-->Ser mutant structures were, in general, very similar to their wild-type counterparts, even though the replacements introduce a hydroxyl group. This is in part because the introduced serines are all within alpha-helices and at congested sites can avoid steric clashes with surrounding atoms by making a hydrogen bond to a backbone carbonyl oxygen in the preceding turn of the helix. The three substituted threonine side chains essentially superimpose on their valine counterparts but display somewhat larger conformational adjustments. The results illustrate how a protein structure will adapt in different ways to avoid the presence of an unsatisfied hydrogen bond donor or acceptor. In the most extreme case, Val 149-->Thr, which is also the most destabilizing variant (delta delta G = 2.8 kcal/mol), a water molecule is incorporated in the mutant structure in order to provide a hydrogen-bonding partner. The results are consistent with the view that many hydrogen bonds within proteins contribute only marginally to stability but that noncharged polar groups that lack a hydrogen-bonding partner are very destabilizing (delta delta G approximately greater than 3 kcal/mol). Supportive of other studies, the alpha-helix propensity of alanine is seen to be higher than that of serine (delta delta G = 0.46 +/- 0.04 kcal/mol), while threonine and valine are similar in alpha-helix propensity. PMID- 8218202 TI - Thermodynamic and alkylation interference analysis of the lac repressor-operator substituted with the analogue 7-deazaguanine. AB - Guanine residues in the lac operator were substituted with the isosteric analogue of 7-deazaguanine. The observed equilibrium dissociation constants for lac repressor binding to substituted operators were measured in 10 mM Tris, 150 mM KCl, 0.1 mM EDTA, and 0.1 mM DTE, pH 7.6, at 25 degrees C, using either a standard equilibrium assay or a competition assay. Of the seven individual sites tested, only three significantly altered the complex affinity. Two of these sites are symmetrically related and are positioned in the major grooves that are known to interact directly with repressor, and the third site is located in the central core region of the operator. The alkylation interference assay, which identifies essential phosphate sites, was used to define the extent of perturbation on the protein-DNA complex by the modified nucleotide. Chemical footprinting data for the singly substituted operator done at a single concentration of protein reflected the alignment of sterically incompatible groups or disruption in the local conformation, but did not appear to alter general phosphate backbone interactions. Similar experiments with a doubly substituted operator revealed that the free energy of binding was an additive combination of each of the individual sites, and the alkylation interference data were similar to the singly substituted and wild-type operators. A constitutive mutant which also had a higher binding constant had a similar alkylation interference pattern. PMID- 8218203 TI - Binding affinities of synthetic peptides, pyridine-2-carboxamidonetropsin and 1 methylimidazole-2-carboxamidonetropsin, that form 2:1 complexes in the minor groove of double-helical DNA. AB - The designed peptides pyridine-2-carboxamidonetropsin (2-PyN) and 1 methylimidazole-2-carboxamidonetropsin (2-ImN) are crescent-shaped analogs of the natural products netropsin and distamycin A. 2-PyN and 2-ImN bind the 5'-TGTCA-3' sequence as antiparallel side-by-side dimers in the minor groove of DNA. The binding affinities of 2-PyN and 2-ImN to four different 5-bp sites on DNA were determined by quantitative MPE-Fe(II) footprint titration and compared with the tripeptide D from distamycin. The binding affinities of D to the sites 5'-TTTTT 3' and 5'-TGTCA-3' are 2.6 x 10(7) and < 1 x 10(5) M-1, respectively (pH 7.0, 100 mM NaCl). 2-PyN binds these sites with similar affinities, 2.3 x 10(5) and 2.7 x 10(5) M-1, respectively. The affinities of 2-ImN to the same two sites are < 5 x 10(4) and 1.4 x 10(5) M-1, respectively. Substitution of an N-methylpyrrole-2 carboxamide of the distamycin tripeptide by 1-methylimidazole-2-carboxamide has changed the specificities for the two binding sites by a factor of 10(3). The data for 2-PyN and 2-ImN binding the 5'-TGTCA-3' site are best fit by a cooperative binding curve consistent with 2:1 peptide-DNA complexes. PMID- 8218204 TI - The glutamyl-tRNA synthetase of Escherichia coli contains one atom of zinc essential for its native conformation and its catalytic activity. AB - The glutamyl-tRNA synthetase of Escherichia coli contains one atom of zinc. This metal ion is strongly bound, as it is not removed by 8 M urea. Slow removal of the zinc at 4 degrees C in the presence of the specific chelating agent, 1,10 phenanthroline, is proportional to the loss of aminoacylation activity and to the presence of a more open conformer of the enzyme. This conformer migrates more slowly than the native enzyme during gel electrophoresis under nondenaturing conditions and binds tRNA(Glu). Infrared spectroscopy measurements show that it differs from the native enzyme by a lower alpha-helix content and a higher proportion of beta-sheet and unordered structures. ATP protects the enzyme against 1,10-phenanthroline-mediated zinc removal, suggesting that the zinc binding region is closely associated with the catalytic site. Additional support for this conclusion comes from the presence of zinc in the 27-kDa N-terminal half of the enzyme and in a 10-kDa fragment. The latter is homologous to the tRNA acceptor helix binding domain of E. coli glutaminyl-tRNA synthetase. The presence of the conserved CYC motif in this domain of the zinc-containing glutamyl-tRNA synthetases of E. coli and Bacillus subtilis, and its absence in that of Thermus thermophilus and the E. coli glutaminyl-tRNA synthetase which do not contain zinc, suggest that the cysteines of this motif and the C- and H-rich 125CRHSHEHHX5C138 segment present in the 10-kDa zinc-binding fragment are involved in zinc binding by the glutamyl-tRNA synthetase of E. coli. PMID- 8218205 TI - 2'-C-methyladenosine and 2'-C-methyluridine 5'-diphosphates are mechanism-based inhibitors of ribonucleoside diphosphate reductase from Corynebacterium nephridii. AB - The interaction of the adenyosylcobalamin-dependent ribonucleoside diphosphate reductase of Cornyebacterium nephridii with 2'-C-methyladenosine 5'-diphosphate (2'-MeADP) and 2'-C-methyluridine 5'-diphosphate (2'-MeUDP) has been investigated. The nucleotide analogs are converted to adenine and uracil, respectively, suggesting that they may be mechanism-based inhibitors. In addition, both analogs generate nucleotides with properties expected for the 2' deoxy-2'-C-methylnucleotides. The nucleoside obtained after enzymatic dephosphorylation of the product formed from 2'-MeADP has been identified as 2' deoxy-2'-C-methyladenosine by 1H NMR and mass spectroscopies. Adenine is the major product derived from 2'-MeADP, indicating that the degradation pathway predominates. During the reaction, the carbon-cobalt bond of the coenzyme is cleaved irreversibly to yield 5'-deoxyadenosine and cob(II)alamin. 2'-MeADP is a potent competitive inhibitor of the reduction of the purine nucleotides ADP and GDP, while 2'-MeUDP competitively inhibits the reduction of the pyrimidine nucleotides UDP and CDP. 2'-MeADP is a very effective promoter of the tritium exchange reaction between [5'-3H2]adenosylcobalamin and the solvent, indicating that the exchange reaction is an integral part of the overall reduction. All these observations are consistent with the reaction mechanism proposed by Stubbe and co-workers [Harris, G., Ashley, G. W., Robins, M. J., Tolman, R. L., & Stubbe, J. (1987) Biochemistry 26, 1895-1902 (1987); Stubbe, J. (1990) J. Biol. Chem. 265, 5329-5332] in which they suggest that the partitioning between reduction and inactivation occurs at the level of the 2'-deoxy-3' ketoribonucleotide intermediate. PMID- 8218206 TI - Site-directed mutagenesis of putative active-site amino acid residues of 3,2 trans-enoyl-CoA isomerase, conserved within the low-homology isomerase/hydratase enzyme family. AB - During beta-oxidation of unsaturated fatty acids, mitochondrial 3,2-trans-enoyl CoA isomerase (mECI) converts 3-cis- or 3-trans-enoyl-CoA intermediates into their 2-trans isomers. The cDNA-derived amino acid sequence of mECI shows weak but significant homologies to the peroxisomal trifunctional enzyme (pTFE), the alpha-subunit of the fatty acid degradation complex from Escherichia coli (FadB), the mitochondrial 2-enoyl-CoA hydratase (mECH), the naphthoate synthase encoded by the menB gene from Bacillus subtilis (MenB), and the 4-chlorobenzoyl-CoA dehalogenase from Pseudomonas sp. (CBDH). These proteins from the isomerase/hydratase enzyme family. Tyr-150, Arg-151, and Asp-211 of the mECI are the only amino acids with protic side chains conserved within the enzymes with isomerase activity (pTFE and FadB). These amino acids are exchanged in the remaining enzymes of the isomerase/hydratase family. Glu-165 is conserved in all enzymes with isomerase and/or hydratase activity (pTFE, FadB, and mECH). We argue that these amino acids are possibly involved in the proton transfer at the active site of mECI. To test this hypothesis, mECI was functionally expressed in E. coli. The recombinant enzyme (rmECI) exhibits the same specific activity as the enzyme from rat liver. Exchange of the candidate active-site amino acids by site directed mutagenesis revealed that Tyr-150 is not involved in isomerase catalysis. The exchange of Arg-151 and Asp-211 leads to a reduced expression of the recombinant enzyme accompanied by a reduced specific activity. The replacement of Glu-165 by Gln leads to a strongly reduced enzymatic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218207 TI - Intramolecular electron transfer in cytochrome o of Escherichia coli: events following the photolysis of fully and partially reduced CO-bound forms of the bo3 and oo3 enzymes. AB - The events which follow photolysis of CO-inhibited fully reduced and CO-bound mixed-valence cytochrome o have been studied in two variants of the enzyme, one of which contains heme B at the low-spin site (bo3) and the other of which contains heme O (oo3). For this, isolated enzyme was prepared from three different strains of Escherichia coli which produce these two variants in different relative amounts [Puustinen, A., Morgan, J. E., Verkhovsky, M., Thomas, J. W., Gennis, R. B., & Wikstrom, M. (1992) Biochemistry 31, 10363-10369]. In both types of enzyme microsecond electron redistribution was observed from the oxygen-binding heme to the low-spin heme. In the bo3 enzyme, the rate was similar to that in the bovine enzyme (3 microseconds), but in the oo3 enzyme, it was several times slower. However, in both types of cytochrome o, the same electron redistribution process was also apparently observed on other time scales, some faster and some slower. The rate of CO rebinding in the mixed-valence enzyme was found to be slower than in the fully reduced enzyme, apparently because of the subpopulation of oxidized oxygen-binding heme produced by the electron redistribution. The extent of this electron redistribution, and thus the inter heme delta Em, can be calculated from this change in rate. The heme B and heme O containing low-spin sites have Em values about 20 and 50 mV lower, respectively, than the oxygen-binding heme. PMID- 8218208 TI - Truncation of the D2 protein in Synechocystis sp. PCC 6803: a role of the C terminal domain of D2 in photosystem II function and stability. AB - Termination and deletion mutations were introduced near the C-terminal end of the D2 protein in the cyanobacterium Synechocystis sp. PCC 6803 in order to determine the role of the large hydrophilic C-terminal domain of D2 in the function and stability of photosystem II (PS II). The loss of 57 residues from the C-terminal end of D2 (most of the hydrophilic tail) resulted in the loss of D2 and PS II reaction centers from thylakoids. Truncation of 16, 15, 14, or 13 amino acid residues from the C-terminus of D2 resulted in a virtual disappearance of oxygen evolution, a loss of photoautotrophic growth, and a decrease in the number of PS II centers in thylakoids. The loss of 11 C-terminal amino acid residues led to a photoautotrophic mutant that grew at one-half the rate of the wild type under photoautotrophic conditions and that showed a progressive loss of oxygen evolution at high light intensity. Truncation of 9 residues from D2 led to a virtual loss of CP43, presumably because of interference of the mutation with the overlapping ribosome-binding site for psbC translation. To delete smaller portions of D2 and yet not interfere with psbC expression, various deletions were made between the tenth and twentieth amino acid residues from the C-terminal end of D2, resulting in the loss of 8, 7, 4, 3, and 2 residues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218209 TI - Identification and biochemical characterization of the ligand binding domain of the collagen adhesin from Staphylococcus aureus. AB - We have recently shown that the expression of a collagen adhesin is both necessary and sufficient to mediate the attachment of Staphylococcus aureus to cartilage, a complex collagen-containing substrate [Switalski, L. M., Patti, J. M., Butcher, W., Gristina, A. G., Speziale, P., & Hook, M. (1993) Mol. Microbiol. 7, 99-107]. We now report on the localization of the ligand binding site within the 135-kDa S. aureus collagen adhesin. Using deletion mutagenesis in combination with Western ligand blot and direct binding assays, the collagen binding domain (CBD) was localized to a 168 amino acid long segment [CBD(151-318)] within the N terminal portion of the adhesin. Using biospecific interaction analysis, pepsin digested bovine type II collagen was found to contain eight binding sites for CBD(151-318); two binding sites were of "high" affinity (Kd = 3 microM) and six sites were of low affinity (Kd = 30 microM). Short truncations in the terminal flanking regions of CBD(151-318) resulted in two CBDs (180-318 and 151-297) that lacked collagen binding activity. Analysis by circular dichroism of the recombinant CBDs in the far UV revealed similar secondary structures, predominantly beta-sheet, whereas the near-UV spectra indicated dramatic changes in the degree of intermolecular packing (tertiary structure). The deduced amino acid sequence of the ligand binding domain of the collagen adhesin is presented. PMID- 8218210 TI - Identification of multiple glucocorticoid receptor binding sites in the rat osteocalcin gene promoter. AB - The biosynthesis of osteocalcin (OC), a bone-specific, noncollagenous protein, is stringently regulated during differentiation of the osteoblast phenotype. Glucocorticoids, and also 1,25(OH)2D3, mediate the developmental regulation of OC gene transcription. In this study, we established that the -1097 to +23 promoter (pOCZCat) of the rat OC gene confers glucocorticoid responsiveness to both basal and vitamin D-induced OC expression. The presence of multiple glucocorticoid receptor (GR) binding sites in the proximal rat OC gene promoter was determined by the combined use of DNase I footprinting, dimethyl sulfate fingerprinting, and gel mobility shift analysis with glucocorticoid receptor protein. One glucocorticoid receptor binding element (GRE) resides immediately downstream of the TATA box (-16 to -1). In vivo activity was established by cotransfection of ROS 17/2.8 osteosarcoma cells with an OC-CAT construct in the presence of cloned GRE sequences (wild type or mutant) as competitors. A putative second, less protected GR binding site is located further upstream in the OC gene basal promoter within the region overlapping the TATA box. This is in direct contrast to the organization of GREs in the human OC proximal promoter wherein GR binding at the upstream GRE overlapping the TATA is stronger than at the downstream GRE. In addition, we detected sequence-specific binding of GR protein to another basal promoter element, the OC box (-99 to -76), which contains a central CCAAT motif. The presence of multiple GR binding sites in the rat OC gene proximal promoter indicates that regulation of basal and vitamin D-enhanced transcription by glucocorticoids may involve the integrated activities of multiple, independent GREs. PMID- 8218211 TI - Mode of dimerization of HIV-1 genomic RNA. AB - Retroviral genomes consist of two identical RNA molecules joined noncovalently near their 5' ends, at domains called dimerization linked sequences (DLS). This physical linkage of the genomic RNAs is considered important for the control of several steps in the viral life cycle, such as recombination, translation, and encapsidation. The putative DLS of human immunodeficiency virus-1 (HIV-1), a 111 nucleotide, purine-rich stretch of RNA, has been found necessary and sufficient for a salt-induced dimerization of the genome in vitro. Our investigation into the mechanism of this dimerization reveals sharply varying influences of the different alkali cations on both the formation and the stabilization of the dimer, a pattern closely related to that of telomeric G-DNA complexes. To probe this phenomenon, we have carried out experiments using short antisense DNA oligomers to define the segments of the DLS that are required for dimerization and methylation protection to implicate sets of guanines in forming Hoogsteen hydrogen bonds within the dimer. Cumulatively, these data provide further evidence for the existence of guanine quartets within the dimerized HIV-1 DLS. We propose models in which guanine quartets not only allow the homodimerization of HIV-1 and other retroviral genomic RNAs but also permit the two RNA strands in a dimer to exist in an overall parallel orientation, as has been observed by electron microscopy. PMID- 8218212 TI - Evidence for crystal environment dominating base sequence effects on DNA conformation: crystal structures of the orthorhombic and hexagonal polymorphs of the A-DNA decamer d(GCGGGCCCGC) and comparison with their isomorphous crystal structures. AB - We have determined the structure of the A-DNA decamer d(GCGGGCCCGC) in two crystal forms, orthorhombic and hexagonal, at 1.7- and 1.8-A resolution, respectively. In the orthorhombic form, the fifth guanine residue has nearly trans-trans conformations for the alpha-gamma backbone torsions, as in the isomorphous orthorhombic structure d(CCCGGCCGGG) [Ramakrishnan, B., & Sundaralingam, M. (1993) J. Mol. Biol. 231, 431-444]. However, in the hexagonal form, the eighth cytosine residue adopts the trans-trans conformations for the backbone alpha-gamma torsions, as in the isomorphous hexagonal structure d(ACCGGCCGGT) [Frederick, C. A., Quigley, G. J., Teng, M.-K., Coll, M., van der Marel, G. A., van Boom, J. H., Rich, A., & Wang, A. H.-J. (1989) Eur. J. Biochem. 181, 295-307]. Even though the average helix and base-pair parameters are nearly the same in the two polymorphous crystal forms having the same sequence, many of the base-dependent local helix parameters are quite different. However, in the isomorphous crystal forms, in spite of the differing base sequences, the local helix and base-pair parameters of the duplexes are nearly the same. This indicates that, in crystals, the local conformation of a DNA structure is affected severely by the crystal packing environment rather than by the base sequence. PMID- 8218213 TI - Relative probability of mutagenic translesion synthesis on the leading and lagging strands during replication of UV-irradiated DNA in a human cell extract. AB - We have previously demonstrated mutagenic bypass of pyrimidine dimers during SV40 origin-dependent replication of UV-irradiated DNA in human cell extracts [Thomas, D. C., & Kunkel, T. A. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7744-7748]. Here we use two vectors having the origin of replication on opposite sides of a lacZ alpha reporter gene to examine the relative probability of mutagenic translesion synthesis on the leading and lagging strands. Although replication of both vectors is inhibited by UVB irradiation in a dose-dependent manner, the covalently closed DNA products of replication contain T4 endonuclease sensitive sites, indicating that bypass of cyclobutane pyrimidine dimers occurred. At fluences of 70 and 100 J/m2, the mutant frequencies obtained with both vectors are substantially higher than with control DNAs. Sequence analysis of mutants obtained with both vectors reveal three types of mutations at frequencies significantly above those obtained from replication of undamaged DNA. These are C ->T transitions, accounting for about two-thirds of the mutants, a small number of CC-->TT substitutions, and complex mutations. Comparing the distribution of C- >T substitutions in the two spectra permits an estimation of the probability of mutagenic translesion replication of the same sequence when replicated as the leading or lagging strand. The data suggest that the overall average UV independent C-->T substitution probability per phenotypically detectable dipyrimidine site is the same during leading and lagging strand replication. However, statistically significant differences are observed when the distribution of C-->T substitutions is considered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218214 TI - NMR studies of 1H NOEs in glycogen. AB - We have examined the cross-relaxation behavior among the protons of oyster glycogen using nuclear Overhauser enhancement (NOE). Steady-state and transient NOEs were generated using low-power CW irradiation and frequency-selective inversions. In D2O, saturation of glycogen H2 and H4' at 3.64 ppm gave a strong negative NOE (eta = -0.74) at H1. The NOE was similar to the value predicted by the correlation time (tau c) calculated from the T1 and T2 of glycogen H1 in D2O assuming an isotropic rigid motor dipole-dipole model. Selective inversion of H2 and H4' gave a transient NOE at H1. In D2O, selective inversion of H1 also led to negative transient NOEs in the H2 + H4', H3, and H5 resonances. The magnitude and rates of appearance of the NOEs in H3 and H5 were too large to arise from direct H1-H3 and H1-H5 dipolar interactions, but were consistent with very efficient cross-relaxation leading to large second-order NOEs. The glycogen H1 NOE in H2O was also studied. Replacement of D2O with H2O as solvent significantly reduced the steady-state NOE at H1 following saturation of H2 + H4'. Saturation of the water resonance caused a large negative NOE at H1 (eta = -0.55) consistent with our earlier study which indicated that there was no direct dipolar interaction between H1 and free H2O. PMID- 8218215 TI - Tri- and diglycine backbone rotational dynamics investigated by 13C NMR multiplet relaxation and molecular dynamics simulations. AB - Backbone motional dynamics in tri- and diglycine have been investigated by using 13C NMR multiplet relaxation spectroscopy. Dipolar auto- and cross-correlation times were determined as a function of pH, ionic strength, and temperature. Molecular dynamics simulations and phi,psi bond rotation energy profiles were calculated for insight into the physical nature of backbone rotations that could contribute to 13C relaxation. Various motional models were used to fit the experimental data. For internal glycine G2 in triglycine, restricted and unrestricted rotational diffusion models both underestimate internal correlation times, although they do agree that the axis of fastest internal rotation is directed closely along the C alpha-C bond. For di- and triglycine, significant pH dependencies in cross-correlation times for C-terminal glycines, and more so for those of N-terminal glycines, indicate the importance of the ionization state in internal mobility of terminal backbone positions. For terminal glycines, rotational jump models which allow for diffusive-like fluctuations within minima best explain the experimental data. phi,psi rotational fluctuation amplitudes and internal rotational energy barriers derived from the temperature dependence of 13C relaxation parameters, which range from 3 to 5 kcal/mol, agree well with those values calculated in rotational energy profiles. PMID- 8218216 TI - Role of hydrogen bonding to bound dioxygen in soybean leghemoglobin. AB - Electron spin echo envelope modulation (ESEEM) spectroscopy was applied to oxy cobaltous soybean leghemoglobin (oxyCoLb) in D2O at various pH values to investigate electron nuclear superhyperfine coupling to N epsilon of the proximal histidyl imidazole and to exchangeable deuterons. Two spectroscopically distinct forms of oxyCoLb, acid and neutral, were identified. In the acid form, a 0.82-MHz hyperfine coupling to 2H was found, indicating the presence of a hydrogen bond to bound O2. No hyperfine-coupled 2H was found in the neutral form. Nuclear hyperfine and nuclear quadrupole couplings to the proximal histidyl N epsilon in the acid form are smaller than those in the neutral form: Aiso = 2.22 MHz and e2qQ = 1.98 MHz for the acid form; Aiso = 2.90 MHz and e2qQ = 2.22 MHz for the neutral form. The differences are believed to result from the presence of a hydrogen bond to bound O2 in the acid form. A discussion of the contribution of this hydrogen bond to the pH-dependent O2 affinity of leghemoglobin is presented. PMID- 8218217 TI - Crystal structure of cholesterol oxidase complexed with a steroid substrate: implications for flavin adenine dinucleotide dependent alcohol oxidases. AB - Cholesterol oxidase from Brevibacterium sterolicum is a flavin-dependent enzyme that catalyzes the oxidation and isomerization of 3 beta-hydroxy steroids with a double bond at delta 5-delta 6 of the steroid ring backbone. The crystal structure of the free enzyme in the absence of a steroid substrate has previously been determined. In this paper we report the crystal structure of the complex of cholesterol oxidase with the steroid substrate dehydroisoandrosterone, refined at 1.8-A resolution. The final crystallographic R-value is 15.7% for all reflections between 10.0- and 1.8-A resolution. The steroid is buried within the protein in an internal cavity which, in the free enzyme crystal structure, was occupied by a lattice of water molecules. The conformations of a number of side chains lining the active-site cavity have changed in order to accommodate the steroid substrate. A loop region of the structure between residues 70 and 90 differs significantly between the substrate-free and substrate-bound forms of the enzyme, presumably to facilitate binding of the steroid. The hydroxyl group of the steroid substrate is hydrogen-bonded to both the flavin ring system of the FAD cofactor and a bound water molecule. FAD-dependent cholesterol oxidase shares significant structural homology with another flavoenzyme, glucose oxidase, suggesting that it might also be a member of the glucose-methanol-choline (GMC) oxidoreductase family. Although there is only limited sequence homology, a superposition of these two structures reveals a conserved histidine residue within hydrogen-bonding distance of the active-site water molecule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218218 TI - Investigation of the structure of oxidized Pseudomonas aeruginosa cytochrome c 551 by NMR: comparison of observed paramagnetic shifts and calculated pseudocontact shifts. AB - Extensive main-chain and side-chain assignments are reported for the 1H NMR spectrum of ferricytochrome c-551 from Pseudomonas aeruginosa at 323 K and pH 5.2. These were obtained by sequential assignments of two-dimensional scalar and dipolar correlation spectra. The low-spin (S = 1/2) ferric iron in the oxidized state gives rise to extensive contact and pseudocontact shifts for resonances in the ferricytochrome. Total redox-state-dependent shifts were computed by comparison to the previously assigned ferrocytochrome c-551. A set of 179 firmly assigned protons was selected that were expected to experience only pseudocontact shift contributions in the oxidized form. The pseudocontact shifts were calculated for the set by a standard model [Williams, G., Clayden, N. J., Moore, G. R., & Williams, R. J. P. (1985) J. Mol. Biol. 183, 447-460] using the atomic coordinates from the X-ray crystallographic determination of the oxidized form [Matsuura, Y., Takano, T., & Dickerson, R. E. (1982) J. Mol. Biol. 156, 389-409], and effective anisotropy and geometric factors were adjusted to minimize the sum of the squared differences between observed redox-state shifts and calculated pseudocontact shift contributions. The root-mean-squared deviation with the optimized parameters was 0.12 ppm. The optimized model was then used to calculate pseudocontact shifts for other assigned protons outside the basic set. The overall agreement and the lack of any systematic discrepancies provide evidence that there are no major structural differences among the solution and crystal conformations of the oxidized and reduced forms, within the inherent resolution of this computational approach.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218219 TI - Site-directed mutants of the cytochrome bo ubiquinol oxidase of Escherichia coli: amino acid substitutions for two histidines that are putative CuB ligands. AB - The bo-type ubiquinol oxidase of Escherichia coli is a member of the superfamily of structurally related heme-copper respiratory oxidases. The members of this family, which also includes the aa3-type cytochrome c oxidases, contain at least two heme prosthetic groups, a six-coordinate low-spin heme, and a high-spin heme. The high-spin heme is magnetically coupled to a copper, CuB, forming a binuclear center which is the site of oxygen reduction to water. Vectorial proton translocation across the membrane bilayer appears to be another common feature of this superfamily of oxidases. It has been proposed previously that the two adjacent histidines in putative transmembrane helix VII (H333 and H334 in the E. coli sequence) of the largest subunit of the heme-copper oxidases are ligands to CuB. Previously reported mutagenesis studies of the E. coli bo-type oxidase and the aa3-type oxidase of Rhodobacter sphaeroides supported this model, as substitutions at these two positions produced nonfunctional enzymes but did not perturb the visible spectra of the two heme groups. In this work, six different amino acids, including potential copper-liganding residues, were substituted for H333 and H334 of the E. coli oxidase. All of the mutations resulted in inactive, but assembled, oxidase with both of the heme components present. However, cryogenic Fourier transform infrared (FTIR) spectroscopy of the CO adducts revealed that dramatic changes occur at the binuclear center as a result of each mutation and that CuB appears to be absent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218220 TI - Molecular recognition in cytochrome P-450: mechanism for the control of uncoupling reactions. AB - The pathway for utilization of pyridine nucleotide derived reducing equivalents in the cytochrome P-450 monooxygenase systems has three major branch points. The first is a partitioning between autoxidation of a ferrous, oxygenated heme adduct and input of the second reducing equivalent required for monooxygenase stoichiometry. The second is between dioxygen bond scission and release of two electron-reduced O2 as hydrogen peroxide. The third is between substrate hydrogen abstraction initiated by a putative higher valent iron-oxo species and reduction of this intermediate by two additional electrons to produce water in an overall oxidase stoichiometry. For all substrates investigated, the direct release of superoxide at the first branch point never competes with second electron input. In order to elucidate the aspects of molecular recognition of a substrate-P-450 complex which affect these individual branch points in the catalytic cycle, we have measured the NADH-derived reducing equivalents recovered in hydroxylated substrate, hydrogen peroxide, and water for a series of active-site mutants designed to alter the coupling of ethylbenzene hydroxylation. We find that the reaction specificity at the second and third branch points is affected by site directed mutations that alter the topology of the binding pocket. The increased commitment to catalysis observed for all mutants suggests that active-site hydration is important in the uncoupling to form hydrogen peroxide at the second branch point. The liberation of hydrogen peroxide does not correlate with the location of the mutation in the pocket, as expected if the two-electron-reduced dioxygen-bound intermediate is not directly participating in the substrate activation step.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218221 TI - Enzyme-substrate binding interactions of NADPH-cytochrome P-450 oxidoreductase characterized with pH and alternate substrate/inhibitor studies. AB - The pH dependence of the kinetic parameters for the reaction catalyzed by NADPH cytochrome P-450 oxidoreductase (P-450R) has been determined, using various substrates and inhibitors. All Vmax and (V/K) profiles show pKas of 6.2-7.3, for an acidic group that is preferentially unprotonated for catalysis, and of 8.1 9.6, for a basic group that is preferentially protonated for catalysis. The presence of the wrong ionization state for both of these groups is tolerated more at lower ionic strength (300 mM) than at higher ionic strength (850 mM). Ionization of the basic group has a more pronounced effect on binding of substrate (cytochrome c or dichloroindophenol) than on catalysis, since ionization has only a 2-fold effect on Vmax with cytochrome c, and only a 5-fold effect on Vmax with dichloroindophenol, while (V/K) for both substrates continues to drop at high pH with no sign of reaching a plateau. Therefore, this basic group affects predominantly substrate binding and, to a lesser extent, catalysis. It is most likely located on the surface of the protein at the cytochrome c/dichloroindophenol binding site, near the FMN prosthetic group. The NADP+ pKi profile shows a pKa of 5.95 for the 2'-phosphate of NADP+, which is bound to P 450R as the dianion, and a pKa of 9.53 for an enzyme group that must be protonated in order to bind NADP+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218222 TI - Interaction with arginine 597 of NADPH-cytochrome P-450 oxidoreductase is a primary source of the uniform binding energy used to discriminate between NADPH and NADH. AB - Site-directed mutagenesis has been used in conjunction with pH and alternate substrate/inhibitor studies to characterize the interactions between NADPH cytochrome P-450 oxidoreductase (P-450R) and the 2'-phosphate of NADP(H) that provide P-450R with its strong nicotinamide nucleotide specificity. It is known that the 2'-phosphate of NADP(H) is bound to P-450R as the dianion and that interactions between it and residues on P-450R provide 5 kcal/mol of essentially uniform binding energy (preceding paper in this issue). In order to probe these interactions further, Arg597 of P-450R, which is homologous to Arg235 of ferredoxin-NADP+ reductase that forms a salt bridge with the 2'-phosphate of 2' phospho-AMP in the crystal structure of that complex [Karplus, P. A., Daniels, M. J., & Herriott, J. R. (1991) Science 251, 60], was mutated to methionine. The mutant protein, P-450R (R597M), does not appear to have a grossly perturbed tertiary structure on the basis of the observation of similar 31P-NMR chemical shifts for FAD (pyrophosphate) bound to it and wild-type (WT) P-450R, although it is more unstable to urea denaturation. P-450R (R597M) has a Km for NADPH that is 150 times that of P-450R (WT) and a Ki for NADP+ that is 240 times that of P-450R (WT). In contrast, the R597M mutation has only a modest effect on the Km for NADH (0.8 WT) and the Ki for NAD+ (2.9 WT), indicating that Arg597 must have been interacting specifically with the 2'-phosphate of NADP(H). The R597M mutation has relatively little effect on kcat for NADPH (1.2 WT) or NADH (0.6 WT), indicating that the mutation is affecting ground and transition states to essentially the same degree, by removing 3 kcal/mol of uniform binding energy. The NADP+ pKi profile for P-450R (R597M) shows a pKa of 5.78 for the 2'-phosphate of NADP+, which is bound to P-450R (R597M) as the dianion, but the pKa of 9.5 for the preferentially protonated enzymic group observed in the P-450R (WT) profile is no longer present. It is argued then that the 2'-phosphate binding pocket of P-450R (WT) has a high positive charge density (> + 2) and that Arg597, which is in this binding pocket, has a highly perturbed pKa of 9.5. Finally, a general theoretical treatment of the thermodynamic consequences of individual and combined perturbations to complementary interacting groups on enzyme and substrate is presented (see Appendix).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8218223 TI - Aldehyde oxidoreductase activity in Desulfovibrio gigas: in vitro reconstitution of an electron-transfer chain from aldehydes to the production of molecular hydrogen. AB - The molybdenum [iron-sulfur] protein, first isolated from Desulfovibrio gigas by Moura et al. [Moura, J. J. G., Xavier, A. V., Bruschi, M., Le Gall, J., Hall, D. O., & Cammack, R. (1976) Biochem. Biophys. Res. Commun. 72, 782-789], was later shown to mediate the electronic flow from salicylaldehyde to a suitable electron acceptor, 2,6-dichlorophenolindophenol (DCPIP) [Turner, N., Barata, B., Bray, R. C., Deistung, J., LeGall, J., & Moura, J. J. G. (1987) Biochem. J. 243, 755-761]. The DCPIP-dependent aldehyde oxidoreductase activity was studied in detail using a wide range of aldehydes and analogues. Steady-state kinetic analysis (KM and Vmax) was performed for acetaldehyde, propionaldehyde, benzaldehyde, and salicylaldehyde in excess DCPIP concentration, and a simple Michaelis-Menten model was shown to be applicable as a first kinetic approach. Xanthine, purine, allopurinol, and N1-methylnicotinamide (NMN) could not be utilized as enzyme substrates. DCPIP and ferricyanide were shown to be capable of cycling the electronic flow, whereas other cation and anion dyes [O2 and NAD(P)+] were not active in this process. The enzyme showed an optimal pH activity profile around 7.8. This molybdenum hydroxylase was shown to be part of an electron-transfer chain comprising four different soluble proteins from D. gigas, with a total of 11 discrete redox centers, which is capable of linking the oxidation of aldehydes to the reduction of protons. PMID- 8218224 TI - Reduction and loss of the iron center in the reaction of the small subunit of mouse ribonucleotide reductase with hydroxyurea. AB - Ribonucleotide reductase is a key enzyme for DNA synthesis in living cells, and the mechanisms for its reactions with inhibitors are of interest because the inhibitors are potential antiproliferative agents. Protein R2, the small subunit of mouse ribonucleotide reductase, contains a pair of mu-oxo-bridged ferric ions and a tyrosyl free radical in each of its two polypeptide chains. Light absorption spectroscopy was used to probe the reactions of these redox centers with hydroxyurea (HU), a potent inhibitor of iron containing ribonucleotide reductases. In Escherichia coli protein R2, HU reacts with the tyrosyl radical without affecting the iron center. In contrast to the case for the E. coli protein, HU destroys the specific absorbance bands of both the iron center and the radical on a similar time scale in mouse protein R2, and this is accompanied by release of iron from the protein. Anaerobic experiments with the iron chelator bathophenanthroline present during the HU reaction indicate that the iron is released from the mouse R2 protein in the ferrous form after treatment with HU. The reduced iron center, formed by reaction of Fe2+ with mouse apoprotein R2 under anaerobic conditions, was found to be much less stable than the native Fe3+ site in the presence of suitable iron chelators. The observations are of importance for understanding the mode of action of HU on mammalian cells and for the general question of the stability of the iron center of mouse protein R2 in different redox states. PMID- 8218225 TI - Microscopic pathway for the medium-chain fatty acyl CoA dehydrogenase catalyzed oxidative half-reaction: changes in the electronic structures of flavin and CoA derivatives during catalysis. AB - In a previous communication, we demonstrated that the medium-chain fatty acyl CoA dehydrogenase (MCAD) catalyzed conversion of 3-indolepropionyl CoA (IPCoA) to trans-3-indoleacryloyl CoA (IACoA) proceeds via the formation of an intermediary species X that possesses the electronic properties of reduced flavin and highly conjugated CoA product. Since the steady-state turnover of the enzyme-catalyzed dehydrogenation reaction precisely matches with the rate of formation of X [Johnson, J. K., & Srivastava, D. K. (1993) Biochemistry 32, 8004-8013], the latter species appeared to be the likely site for the transfer of electrons to external electron acceptors (e.g., ferricenium hexafluorophosphate, FcPF6). To probe the microscopic pathway for the oxidative half-reaction, we employed a sequential mixing stopped-flow technique utilizing IPCoA as the enzyme substrate and FcPF6 as the electron acceptor. The time-dependent changes in absorption at 450, 415, and 367 nm were measured upon mixing FcPF6 with previously mixed and aged solutions of MCAD-FAD+IPCoA in the stopped-flow syringes. The kinetic traces show an increase (1/tau 1) followed by a decrease (1/tau 2) in absorption at 450 and 415 nm, and a lag (corresponding to the time regime of 1 u 1) followed by an increase in absorption (1/tau 2) at 367 nm. The relaxation rate constants (1/tau's) thus measured remain unaffected, with variations in the aging time; however, the amplitudes of these phases increase up to the aging time of 5 s, after which the amplitudes attain maxima. For an aging time of 5 s, 1/tau 1 and 1/tau 2 show a linear and a hyperbolic dependence on the FcPF6 concentration, respectively. These, coupled with the complementary studies involving butyryl CoA as a nonchromophoric substrate for this enzyme, lead us to propose the following sequence of events during the MCAD-catalyzed oxidative half-reaction: (1) The enzyme-catalyzed oxidative half-reaction proceeds via the formation of a collision complex between X and FcPF6 during the fast (1/tau 1) relaxation phase. (2) The reduced flavin moiety of X is oxidized via (rapid) transfer of electrons to FcPF6 within the collision complex, without formation of a detectable (metastable) flavin semiquinone intermediate. (3) The transfer of electrons is accompanied by changes in the electronic structures of both the flavin and IACoA moieties within the enzyme-IACoA complex. The electronic structure of this newly formed complex is exactly the same as that formed upon isomerization of the MCAD FAD-IACoA complex [Johnson, J. K., Wang, Z. X., & Srivastava, D. K. (1992) Biochemistry 31, 10564-10575].(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8218226 TI - PACE4 is a member of the mammalian propeptidase family that has overlapping but not identical substrate specificity to PACE. AB - Proteins that transit the constitutive pathway of secretion frequently require proteolytic processing after a pair of basic amino acids to attain their full functional activity. A ubiquitously expressed calcium-dependent subtilisin-like serine protease, named PACE or furin, can cleave precursor polypeptides specifically at pairs of basic amino acids where an arginine residue is present in the P4 position. Another member of this protease family, PACE4, was cloned recently by a PCR-based strategy and was also shown to be ubiquitously expressed. We have expressed PACE4 by transient DNA transfection of COS-1 cells and have shown that the cDNA encodes a 120-kDa polypeptide that is present in cell extracts but not in conditioned medium of transfected cells. The substrate specificities of PACE and PACE4 for cleavage of pro-von Willebrand factor were studied in parallel using a transient DNA cotransfection system. Like PACE, PACE4 was able to process pro-vWF to its mature form, and efficient cleavage required both the P4 arginine and the P2 lysine. These data, taken together with previously published data showing that PACE4 cannot process pro-factor IX, demonstrate that PACE and PACE4 have overlapping but not identical substrate specificities. Further differences between PACE and PACE4 specificities were elucidated by monitoring inhibition of processing activity mediated by the serine protease inhibitor alpha 1-antitrypsin Pittsburgh mutant. Pro-vWF processing by PACE was inhibited by expression of the alpha 1-antitrypsin Pittsburgh mutant, whereas processing of pro-vWF by PACE4 was not affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218227 TI - Binding of phenol and analogues to alanine complexes of tyrosine phenol-lyase from Citrobacter freundii: implications for the mechanisms of alpha,beta elimination and alanine racemization. AB - We have examined the interaction of Citrobacter freundii tyrosine phenol-lyase with both L- and D-alanine. This enzyme catalyzes the racemization of alanine as a side reaction, in addition to the physiological beta-elimination of L-tyrosine to give phenol and ammonium pyruvate. The steady-state kinetic parameters for alanine racemization, kcat and Km, for D-alanine are 0.008 S-1 and 32 mM, respectively, while those for L-alanine are 0.03 S-1 and 11 mM. Incubation of tyrosine phenol-lyase with either L- or D-alanine forms a quinonoid complex that exhibits a strong peak at 500 nm. The presence of K+ increases the intensity of the 500-nm absorption with L-alanine, but decreases the intensity of the peak with D-alanine. Rate constants for the formation of these quinonoid intermediates and the effects of phenol and analogues on the reaction with either L- or D alanine have been studied by rapid-scanning and single-wavelength stopped-flow spectrophotometry. Phenol binds to all the intermediates of tyrosine phenol-lyase with L- and D-alanine, but most strongly to the external aldimine complex, resulting in a decrease in the absorbance at 500 nm at equilibrium. Pyridine N oxide binds selectively to the quinonoid complex of alanine, and thus causes an increase in the absorbance at 500 nm at equilibrium. 4-Hydroxypyridine causes a decrease in absorbance at 500 nm during the fast phase, but an increase in absorbance at 502 nm in a subsequent slow relaxation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218228 TI - Glycosylation-dependent activity of baculovirus-expressed human liver carboxylesterases: cDNA cloning and characterization of two highly similar enzyme forms. AB - A cDNA, designated hCE, encoding the entire sequence of a carboxylesterase, was isolated from a human liver lambda gt11 library. The hCE-deduced protein sequence contained 568 amino acids, including an 18 amino acid signal peptide sequence, and had a calculated molecular mass of the mature protein of 60,609 Da. A second cDNA, designated hCEv, was isolated from the same lambda gt11 library and contained a 3-bp deletion resulting in the loss of the final amino acid in the signal peptide sequence (Ala-1) and a second 3-bp deletion leading to an in-frame loss of Gln345. Expression of mRNA corresponding to both hCE and hCEv was detected in eight adult human liver samples, with individual levels varying 5 fold (hCE) and 12-fold (hCEv). A single immunoreactive protein was detected in 13 adult human liver samples when probed with antibody directed against a rat carboxylesterase. Based on allele-specific oligonucleotide hybridizations, we believe that the hCE and hCEv cDNAs represent two distinct members of the carboxylesterase family. The carboxylesterase genes were localized to human chromosome 16 using a somatic cell hybrid mapping strategy. Baculovirus expression of hCE in Sf9 cells produced a protein with an estimated molecular mass of 59,000 Da. This enzyme was able to hydrolyze aromatic and aliphatic esters but possessed no catalytic activity toward amides or a fatty acyl CoA ester. Baculovirus-mediated expression of the hCEv cDNA yielded a second protein of 56,000 Da resulting from inefficient N-glycosylation of the hCEv protein. Although the substrate specificity for the hCEv protein was identical to that of expressed hCE for any given substrate, the specific activity for the hCE protein was always higher than that for the hCEv protein. Tunicamycin inhibition studies provided the first evidence that N-glycosylation of these luminal enzymes is essential for maximal catalytic activity. PMID- 8218229 TI - Identification of important residues within the putative nucleoside binding site of HSV-1 thymidine kinase by random sequence selection: analysis of selected mutants in vitro. AB - Random sequence mutagenesis in conjunction with genetic complementation was used to map the function of amino acid residues within the putative nucleoside binding site of the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK). Six codons of the putative nucleoside binding site of the HSV-1 tk were substituted by a duplex of extended oligonucleotides containing 20% random sequences. Approximately 260 mutants were screened for the ability to genetically complement a TK-deficient Escherichia coli. Of those screened, 32% conferred TK activity. Approximately 60% of the TK positive clones contained single amino acid changes, 23% contained double changes, and 13.4% encoded the wild-type TK amino acid sequence. A small percentage of clones, 2.4% and 1.2%, contained triple or quadruple alterations, respectively. Three residues (D162, H163, and R164) appeared to be highly conserved especially with regard to the type of residues able to substitute. Secondary screening results indicated that several of the mutants had higher affinities for acyclovir and/or 3'-azido-3'-deoxythymidine than thymidine in complementation assays. In addition, a number of clones were unable to form colonies on selection medium at elevated temperatures (42 degrees C). Eight selected mutants were subcloned into an in vitro transcription vector and the derived transcripts used to program a rabbit reticulocyte lysate cell free translation system. Biologically active translation products were then analyzed in vitro for thymidine kinase activity, for thermal stability, and for the ability to phosphorylate selected nucleoside analogues. Two of the eight mutants had an elevated thymidine kinase activity, two were significantly thermolabile, and three exhibited enhanced efficiency in phosphorylation of nucleoside analogues. PMID- 8218230 TI - Transcriptional regulation of the Xenopus laevis B beta fibrinogen subunit gene by glucocorticoids and hepatocyte nuclear factor 1: analysis by transfection into primary liver cells. AB - The blood-clotting protein fibrinogen is composed of three subunits, designated A alpha, B beta, and gamma, which are encoded by a family of related genes. As part of the acute-phase response, expression of the fibrinogen genes is coordinately regulated in the liver by glucocorticoids. To understand the factors underlying this hormonal response, we have examined control of transcription from fibrinogen gene fragments transfected into hepatocytes from the frog Xenopus laevis. This analysis is the first in any species to define transcriptional regulatory elements for the fibrinogen genes by transfection into primary liver cells, rather than liver-derived cell lines. A transfection vector was constructed containing the Xenopus B beta gene transcription start site and 1293 bp of the 5' flanking sequence linked to the firefly luciferase gene. When this construct was transfected into primary liver parenchymal cells, luciferase expression was induced approximately 14-fold by glucocorticoids, an increase similar to the transcriptional stimulation of the endogenous B beta subunit gene. DNA fragments with as little as 284 bases of upstream sequence retained full hormone responsiveness. This region contains a sequence resembling the canonical glucocorticoid response element (GRE) at bases -148 to -162. Deletions or specific point mutations eliminating this putative GRE led to complete loss of glucocorticoid inducibility. Physical association of the steroid hormone receptor with this functional GRE was demonstrated with a truncated form of the rat glucocorticoid receptor containing the DNA-binding domain. A second possible GRE at positions -526 to -540 was not hormone-responsive, in either the presence or the absence of the more proximal GRE. The regulatory region also has a sequence similar to the binding site for a liver-specific transcription factor, hepatocyte nuclear factor 1 (HNF-1), at positions -120 to -132. Specific point mutations in the HNF-1-binding site, in a construct containing a wild-type GRE, reduced promoter activity by a factor of 10, while stimulation by glucocorticoids was retained. Binding studies confirmed specific interaction between this site and the transcription factor HNF-1 alpha from mouse. Thus, we have identified a GRE sufficient to account for full glucocorticoid inducibility and an HNF-1 site close to the promoter that are major determinants of transcriptional control of the Xenopus fibrinogen B beta subunit gene in cells from normal liver tissue. PMID- 8218231 TI - The allosteric transition of the insulin hexamer is modulated by homotropic and heterotropic interactions. AB - The allosteric behavior of the Co(II)-substituted insulin hexamer has been investigated using electronic spectroscopy to study the binding of different phenolic analogues and singly charged anions to effector sites on the protein. This work presents the first detailed, quantitative analysis of the ligand induced T- to R-state allosteric transition of the insulin hexamer. Recent studies have established that there are two ligand binding processes which stabilize the R-state conformation of the Co(II)-substituted hexamer: the binding of cyclic organic molecules to the six protein pockets present in the Zn(II)-R6 insulin hexamer [Derewenda, U., Derewenda, Z., Dodson, E. J., Dodson, G. G., Reynolds, C. D., Smith, G. D., Sparks, C., & Swensen, D. (1989) Nature 338, 594 596] and the coordination of singly charged anions to the His(B10) metal sites [Brader, M.L., Kaarsholm, N.C., Lee, W.K., & Dunn, M.F. (1991) Biochemistry 30, 6636-6645]. The R6 insulin hexamer is stabilized by heterotropic interactions between the hydrophobic protein pockets and the coordination sites of the His(B10)-bound metal ions. The binding studies with 4-hydroxybenzamide, m-cresol, resorcinol, and phenol presented herein show that, in the absence of inorganic anions, the 4-hydroxybenzamide-induced transition, with a Hill number of 2.8, is the most cooperative, followed by m-cresol, phenol, and resorcinol with Hill numbers of 1.8, 1.4, and 1.2, respectively. The relative effectiveness of these ligands in shifting the allosteric equilibrium in favor of the Co(II)-R6 hexamer was found to be resorcinol > phenol > 4-hydroxybenzamide > m-cresol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218232 TI - Characterization of a G-quartet formation reaction promoted by the beta-subunit of the Oxytricha telomere-binding protein. AB - Telomeres, the ends of linear chromosomes, typically consists of tandem repeats of a simple guanine-rich sequence. Telomeric DNA is able to form intermolecular G quartet structures. The beta-subunit of the Oxytricha telomere-binding protein acts as a molecular chaperone to promote the formation of dimers and specific higher order complexes of telomeric DNA stabilized by G-quartets; these reactions occur under physiological conditions in vitro. In the present article, we show that, at saturating protein concentrations (> or = 200 nM), beta-mediated G quartet formation is a first-order reaction with respect to DNA concentration, with k approximately 1 h-1 at 37 degrees C. In contrast, the protein-independent reaction is a second-order reaction. The beta-subunit enhances the rate of G quartet formation by 10(5)-10(6)-fold at a telomeric DNA concentration of 20 nM. The beta-mediated higher order complexes are identified as parallel four-stranded tetramers of telomeric DNA (G4-DNA). Poly-L-lysine also promotes formation of the tetramers, but not dimers. These DNA structures were studied by irreversible thermal melting experiments and probed by annealing to different complementary strands. Guanine residues important for structure formation were analyzed by methylation interference experiments. On the basis of these data, models for the beta-mediated structures are proposed, and possible mechanisms for the beta mediated reaction are discussed. In addition, we found that the beta-subunit promotes the annealing of two complementary strands into a duplex, as do many other basic proteins. However, not all proteins with annealing-promoting activity are active in the formation of G-quartet structures. The activity of the telomere protein in promoting the formation of telomeric DNA structures may enable chromosome-chromosome association or the regulation of telomerase activity in vivo. PMID- 8218233 TI - Importance of exocyclic base functional groups of central core guanosines for hammerhead ribozyme activity. AB - The three guanosines of the central core of a hammerhead ribozyme were replaced by 2-aminopurine ribonucleoside, xanthosine, isoguanosine, inosine, and deoxyguanosine. These analogues were incorporated by automated solid-phase synthesis, with the exception of isoguanosine. This was introduced by ligating a donor, which carried the isoguanosine at its 5'-end, and an acceptor oligoribonucleotide by a T4 DNA ligase-catalyzed reaction. Most of these modifications lowered the rate constant of cleavage by the hammerhead ribozyme drastically. Inspection of the possible hydrogen-bonding interactions disturbed by these modifications suggests that there is no G12A9 or A13G8 mismatched base pair in the central region. Increasing the Mg2+ concentration from 10 to 50 mM did not enhance these rates appreciably. This makes it improbable that the guanosines, including their 2'-hydroxyl groups, are involved in the binding of the catalytically active Mg2+. Transition-state destabilizing energies of 0.6-4.7 kcal mol-1 suggest that essentially all guanosines are involved in a hydrogen bonding network. PMID- 8218234 TI - Conformation-selective DNA strand breaks by dynemicin: a molecular wedge into flexible regions of DNA. AB - We present evidence that the enediyne antitumor antibiotic dynemicin recognizes and cleaves conformationally flexible regions of DNA. This is based on specific strand breaks at mismatches, bulges, and nicks as determined by high-resolution sequencing gels. On the basis of the weak association constant of dynemicin for DNA, it is expected that these more flexible regions would be preferred sites. In addition, the DNA unwinding behavior of dynemicin and the absorption spectrum of the dynemicin-DNA complex are strongly indicative of its intercalative binding with DNA. The results allow us to propose dynemicin as a molecular wedge that binds to the DNA by intercalating into the minor-groove side of conformationally flexible regions of DNA. Presumably, DNA local flexibility is able to create an open pocket in the minor groove, permits facile intercalation of dynemicin, and then increases the chances of its DNA damaging event. Implications for the biological action of dynemicin have also been discussed. PMID- 8218235 TI - DNA conformational change produced by the site-specific interstrand cross-link of trans-diamminedichloroplatinum(II). AB - The DNA distortion produced by the interstrand cross-link of trans diamminedichloroplatinum-(II) has been described by means of gel electrophoresis, chemical probes, and molecular mechanics modeling. Synthetic double-stranded oligodeoxyribonucleotides of varying lengths (19-22 base pairs) were synthesized that contained a unique site-specific interstrand cross-link within their central sequence d(TGCT)/d(AGCT) between complementary guanine and cytosine residues. We find that the platinated deoxyriboguanosine residue adopts syn conformation. The duplex is distorted on both sides of the cross-link, but the bases are still paired. The distortion introduces some flexibility into the helix. In addition, the double helix is unwound and bent toward the major groove. PMID- 8218236 TI - An efficient screening assay for the rapid and precise determination of affinities between leucine zipper domains. AB - The protein products of the jun and fos oncogenes require a functional protein protein interaction domain, called the "leucine zipper domain", to exert their transcriptional regulatory activity. A scintillation proximity assay was developed in which the biotinylated leucine zipper domain of the Jun protein (275 315) was immobilized on streptavidin-coated microfluorospheres and in which the leucine zipper domain of the Fos protein (160-200) was used as free, labeled ligand. The Fos leucine zipper peptide specifically bound to the Jun leucine zipper peptide, and for the first time, a dissociation constant (Kd = 110 +/- 12 nM in PBS/0.1% Tween) could be determined. Optimal heterodimer formation was reached at neutral pH. Both acidic and alkaline pH decreased the association of the peptides which was, furthermore, completely abolished by 500 mM NaCl, confirming that charged residues are critical for heterodimerization. A commercially obtained recombinant Jun protein competed as efficiently as the Jun leucine zipper peptide for binding to the Fos peptide, confirming the feasibility of using the two leucine zipper peptides to study the interactions between the two transcription factors. We also injected leucine zipper peptides individually into Xenopus oocytes to study whether they would interfere with the activity of the Fos/Jun heterodimer in vivo. Both peptides blocked selectively insulin mediated oocyte maturation with an IC50 in the range of 15 ng per oocyte. In conclusion, the scintillation proximity assay described here may be used to investigate protein-protein interactions mediated by leucine zipper structures and to identify compounds that inhibit leucine zipper association. PMID- 8218237 TI - Characterization of collagen-like peptides containing interruptions in the repeating Gly-X-Y sequence. AB - Glycine is found as every third residue along the entire length of triple helices in fibrillar collagens, but the triple-helix regions of nonfibrillar collagens and other proteins usually contain one or more interruptions in this repeating pattern. A set of four peptides was designed to model the effect of interruptions in the (Gly-X-Y)n repeating pattern on triple-helix formation, stability, and folding. Into the middle of the stable triple-helical peptide (Pro-Hyp-Gly)10, an interruption was introduced representing one of the four possible categories: a glycine deletion, a deletion of a hydroxyproline (Y position), an alanine insertion, or a glycine to alanine substitution. As shown by sedimentation equilibrium, NMR, and CD studies, the introduction of an interruption still allowed formation of trimers in solution, but with marked decrease in stability. The degree of destabilization and the thermodynamic basis for the loss of stability depended on the type of interruption. The glycine substitution and alanine insertion were the least disruptive, followed by the hydroxyproline deletion, with the glycine deletion being the most destabilizing. Our results suggest that the breaks in these peptides affect both the triple-helical conformation and the monomer conformation. These studies provide a basis for considering the structural and functional consequences of different kinds of interruptions in collagen. PMID- 8218239 TI - Role of disulfide linkages in tachyplesin-lipid interactions. AB - In order to elucidate the role of the two disulfide linkages of tachyplesin I (T SS), a membrane-acting cyclic antimicrobial peptide from Tachypleus tridentatus, we synthesized the acyclic analog (T-Acm) with the four SH groups protected by acetamidomethyl groups and also investigated the interactions of these peptides with lipid bilayers. T-SS induced leakage of calcein from egg yolk L-alpha phosphatidylglycerol large unilamellar vesicles (PG LUVs) at peptide concentrations 1 order of magnitude smaller than those at which leakage was induced by T-Acm, which coincides with the stronger antimicrobial activities of T SS. The micellization of PG LUVs was also more efficient for the cyclic peptide. Fluorescence titration studies revealed that binding affinities of both peptides to the PG membranes were similar. Fourier transform infrared polarized attenuated total reflection spectroscopy and fluorescence quenching experiments demonstrated that T-SS and T-Acm both form amphiphilic antiparallel beta-sheet structures in the membranes. They are formed in such a way that the sheet planes lie parallel to the membrane surface with the sheet hydrophobic surfaces penetrating slightly into the hydrophobic region of the bilayers. Furthermore, the observation that the linear T-Acm, the weaker membrane permeabilizer, caused a far more serious membrane disruption suggests the possibility that the mechanisms of membrane permeabilization by the cyclic peptide are different from those by the linear peptide, the latter being the disruption of the lipid organization. PMID- 8218238 TI - Acyl structure regulates galactosylceramide's interfacial interactions. AB - Galactosylceramides (GalCer) with homogeneous acyl chains containing zero, one, or two cis double bonds have been synthesized and characterized at an argon aqueous buffer interface using a Langmuir film balance. Both surface pressure and surface potential were measured as a function of molecular area at 24 degrees C. N-Lignoceroylgalactosylsphingosine (N-24:0-GalSph), N stearoylgalactosylsphingosine (N-18:0-GalSph), and N palmitoylgalactosylsphingosine (N-16:0-GalSph) form condensed films that are similar to that of bovine brain GalCer, which contains long saturated and mono unsaturated acyl chains, almost half being hydroxylated. In contrast, a bovine brain GalCer subfraction (NFA-GalCer) that is devoid of the hydroxylated acyl chains displays an apparent two-dimensional phase transition near 9.0 mN/m at 54 A2/molecule. To determine the role of acyl unsaturation in regulating NFA GalCer's surface behavior, GalCer derivatives containing different mono unsaturated acyl residues were investigated. N-Nervonoyl-galactosylsphingosine (N 24:1 delta 15-GalSph) and N-docosenoylgalactosylsphingosine (N-22:1 delta 13 GalSph) show liquid-expanded to -condensed phase transitions in their force-area isotherms at 10 and 35 mN/m, respectively. Introduction of acyl chains that are short and saturated [e.g., N-decanoylgalactosylsphingosine (N-10:0-GalSph)] or that are long but contain two cis double bonds [e.g., N linoleoylgalactosylsphingosine (N-18:2 delta 9,12-GalSph)] causes GalCer to display only liquid-expanded behavior at 24 degrees C. The surface potentials (delta V) of the condensed GalCer derivatives with long saturated acyl residues were quite similar and were over 100 mV higher than that of bovine brain GalCer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218240 TI - Calcium-dependent annexin V binding to phospholipids: stoichiometry, specificity, and the role of negative charge. AB - Annexin V is a Ca(2+)-dependent, phospholipid-binding protein that may have one or more membrane-related functions. The binding of annexin V to phospholipids in a detergent micelle matrix was studied to attempt to determine directly the stoichiometry of specific phospholipid-binding sites and the importance of negative charge. When annexin V binds to phospholipids, a large increase (severalfold) of the emission intensity of tryptophan 187 is observed. This intensity change was used to monitor the binding to phosphatidylcholine (PC) or phosphatidylserine (PS) at varying ratios with the detergent, octaethylene glycol monododecyl ether (C12E8). No binding to PC alone in these micelles could be observed, while approximately 10 PS molecules per micelle were required to observe binding. However, inclusion of negatively charged amphiphiles in the micelles, such as oleic acid or dodecyl sulfate, allowed the observation of binding to PC and decreased the number of phospholipids per micelle necessary for binding to both PS and PC. By including increasing proportions of dodecyl sulfate in the C12E8 micelles, a minimum average number of PS or PC per micelle of approximately 3-4 was required for complete binding. Labeling with photoreactive phospholipids under similar conditions led to an average of approximately 4-5 phospholipids covalently bound per annexin V monomer. Since annexin V has four similar domains, it is reasonable to suggest that one phospholipid binding site is associated with each domain, although as few as three functional domains may be sufficient for binding. Efficient binding required certain structural features of the phospholipid, including a phosphate group, an sn-2 acyl chain, and at least a few carbons on the sn-2 chain. Phospholipid headgroups were almost irrelevant, except for important surface charge effects on the interfacial ionic double layer. A negative surface charge on the micellar aggregate nonspecifically increases the Ca2+ concentration near the micelle surface and may also directly enhance the affinity of annexin V for phospholipids, as shown by the decreased two-dimensional phospholipid concentration necessary for binding. The ability to bind to zwitterionic phospholipids in the presence of a nonspecific negative surface charge may be relevant to the extracellular functions of this protein. Relatively weak individual phospholipid-binding sites that easily exchange were observed, suggesting rapid exchange of phospholipids between the sites on membrane-bound annexin V. These data suggest a working hypothesis that includes approximately four binding sites specific for phospholipid phosphate groups and sn-2 acyl chains.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8218241 TI - Human erythrocyte membrane lipid asymmetry: transbilayer distribution of rapidly diffusing phosphatidylserines. AB - Human erythrocytes were incubated with sonicated vesicles composed of diheptanoyl , dioctanoyl-, didecanoyl-, or dimyristoylphosphatidylserine, and the transbilayer distribution of the incorporated foreign lipid was examined by monitoring changes in cell morphology (Daleke & Huestis (1989) J. Cell. Biol. 108, 1375). Cells incubated with all phosphatidylserine homologs crenated initially and then reverted to discoid and stomatocytic morphology. Cells exposed to didecanoyl- or dimyristoylphosphatidylserine retained stable stomatocytic morphology during more than 10 h of incubation at 37 degrees C. Cells exposed to the diheptanoyl or dioctanoyl homologs reverted from stomatocytes to discocytes within 1-4 h. This reversion was more rapid for the shorter acyl chain diheptanoylphosphatidylserine. Reversion was accelerated in both cases by vanadate, an inhibitor of the aminophospholipid translocator. Heat denaturation of cytoskeletal proteins had no effect on phosphatidylserine-induced stomatocytosis or on the reversion to discoid shape of cells exposed to the short chained homologs. These observations suggest that the aminophospholipid transporter rather than cytofacial lipid binding sites plays the primary role in maintenance of phosphatidylserine asymmetry in the erythrocyte membrane bilayer. PMID- 8218243 TI - Platelet-derived growth factor AB heterodimer interchain interactions influence secretion as well as receptor binding and activation. AB - Platelet-derived growth factor (PDGF) is a disulfide-linked dimer comprised of two related polypeptide chains. To investigate the effects of an inactivating lesion introduced into one chain of the nascent PDGF dimer, approaches were developed to optimize synthesis, assembly, secretion, and purification of heterodimers between normal PDGF A and wild-type or mutant PDGF B. PDGF AB heterodimers were released into culture fluids less efficiently than PDGF AA, but to a greater degree than the cell-associated PDGF BB. These results suggest that interactions between two chains influence PDGF secretion. Analysis of heterodimers between PDGF A and disabled PDGF B mutants on cells that express either alpha or beta PDGFRs demonstrated that the impaired biologic activity of the mutant PDGF B chain was ameliorated with respect to binding and triggering of alpha PDGFRs. In cells that expressed both receptor types, heterodimers of mutant PDGF B and wild-type PDGF A gained substantially in their ability to recruit and trigger alpha, but not beta, PDGFRs. Partial rescue of impaired PDGF B mutant chain function by dimer formation with a wild-type PDGF A chain implies that interchain interactions markedly affect PDGFR binding and activation. PMID- 8218242 TI - Human serotonin1B receptor expression in Sf9 cells: phosphorylation, palmitoylation, and adenylyl cyclase inhibition. AB - Analysis of the primary protein structure of the human serotonin1B (5-HT1B) receptor reveals consensus sites for phosphorylation and a putative site for palmitoylation. To investigate these posttranslational modifications, we have expressed a c-myc epitope-tagged 5-HT1B (m5-HT1B) receptor in Sf9 cells. This strategy enabled receptors to be detected by immunoblot analysis and purified by immunoprecipitation using a monoclonal antibody, 9E10, specific for the c-myc epitope. Agonist radioligand [3H]5-HT binding studies showed that the expressed 5 HT1B and m5-HT1B receptors displayed the characteristic pharmacological profile of the neuronal 5-HT1B receptor. The expressed receptors displayed both high- and low-affinity states for [3H]5-HT, suggesting that the receptors were coupled to endogenous G-proteins. Indeed, agonist binding to the high-affinity receptor state was regulated in the presence of GTP gamma S, Gpp(NH)p, and pertussis toxin. [32P]ADP-ribosylation experiments identified a major approximately 41-kDa ADP-ribosylated protein present in Sf9 membranes that comigrated with partially purified bovine brain Gi alpha/G(o) alpha subunits. Measurements of adenylyl cyclase activity in membranes from cells expressing m5-HT1B receptors showed that serotonergic agonists mediated the inhibition of adenylyl cyclase activity with a rank order of potency comparable to their affinity constants. Immunoblot analysis of membranes prepared from cells expressing m5-HT1B receptors and photoaffinity labeling of the immunoprecipitated material revealed photolabeled species at approximately 95 and at approximately 42 kDa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218244 TI - Structural conservation in the CheY superfamily. PMID- 8218245 TI - Rotational dynamics of hexaamminecobalt(III) bound to oligomeric DNA: correlation with cation-induced structural transitions. AB - Two common assumptions are that duplex DNA structure shows little sensitivity to ionic conditions and that simple cations bind to DNA in a nonspecific fashion. Here we examine these assumptions using as a model ligand the inorganic cation Co(NH3)6(3+). We find, upon titration with Co(NH3)6(3+), that certain DNA oligonucleotides show pronounced changes in circular dichroism spectra. For oligonucleotides such as d(GGCCGGCC), with contiguous, same-strand guanines, the transition is toward A-DNA characteristics. For those oligonucleotides that manifest such large Co(NH3)6(3+)-induced changes in circular dichroism spectra, 59Co NMR relaxation measurements demonstrate that Co(NH3)6(3+) tumbling motions are greatly inhibited, so that the effective NMR correlation time approaches that of overall tumbling of the DNA oligomer. Very large upfield 59Co chemical shifts are observed for Co(NH3)6(3+) bound to such oligonucleotides. For another class of oligomers, which show no significant changes in the circular dichroism spectrum in the presence of Co(NH3)6(3+), the tumbling motions of bound Co(NH3)6(3+) are largely independent of those of the oligomer, and much more modest 59Co chemical shifts are observed. Oligomers in a third class cause significant rotational inhibition of bound Co(NH3)6(3+), and only modest changes in 59Co chemical shifts. Oligonucleotides in this class appear not to undergo large structural changes in the presence of Co(NH3)6(3+). Within these broad categories, a remarkable variability in 59Co NMR parameters, and in structural perturbations, is apparent for the 13 oligonucleotides that we have examined. PMID- 8218246 TI - pH affects both the mechanism and the specificity of peptide binding to a class II major histocompatibility complex molecule. AB - We have compared the contribution of electrostatic forces in the binding of antigenic peptides to the class II MHC molecule, IEk, at weakly acidic (pH 5.4) and neutral (pH 7.5) pH values. The binding of specific moth cytochrome c (MCC) and hemoglobin (Hb) peptides to IEk is very sensitive to ionic strength at pH 7.5 but not at pH 5.4, indicating that the mechanism of peptide binding is pH dependent. Substitution of the C-terminal Lys in MCC for an Ala residue selectively destroyed peptide binding at neutral pH and increased the dissociation rate at least 30-fold, implicating this residue in the pH-dependent electrostatic interaction. The presence of a C-terminal Lys in many of the peptides that are restricted to IEk suggests that this electrostatic interaction is widely used to bind peptides to this MHC molecule. We also probed the electrostatic environment of the peptide binding groove adjacent to the N terminus of the bound peptide by rapid-diffusion fluorescence energy transfer using a terbium-labeled MCC peptide. In this region of the peptide binding groove, more negative charge is present at pH 7.5 than at pH 5.4. These findings indicate the importance of MHC carboxylates to the mechanism and specificity of peptide binding. The biological importance of having two distinct mechanisms of peptide binding at different pH may be that it acts to broaden the spectrum of antigenic peptides that can be presented to T-cells. PMID- 8218247 TI - Solution oligomerization of the rev protein of HIV-1: implications for function. AB - rev is an RNA-binding protein of human immunodeficiency virus-1 and is required for the expression of incompletely spliced viral transcripts. Oligomerization of rev is thought to be associated with RNA binding and rev function. Here, we have characterized the oligomerization of rev using equilibrium analytical centrifugation. rev is predominantly monomeric at low concentrations, but reversibly polymerizes to produce large aggregates at higher concentrations. The data fit well to an unlimited isodesmic self-association model in which the association constants for the addition of a monomer to each aggregate are equal [K = 1.08 x 10(6) M-1 at 4 degrees C]. The association constant is essentially independent of monovalent salt concentration from 0.15 to 2 M at pH 6-9. Thermodynamic parameters derived from the temperature dependence of the association constant over the limited range of 0-30 degrees C reveal that the primary contribution to the free energy of oligomerization is a large negative enthalpy. Binding of rev to the rev-responsive element of RNA was characterized under the same conditions as the centrifugation experiments using a nitrocellulose filter assay. rev binds to the RRE at a protein concentration where rev is predominantly monomeric, suggesting that solution multimerization of rev is not required for rev function. PMID- 8218248 TI - Thermodynamics and premelting conformational changes of phased (dA)5 tracts. AB - Using synthetic 45 bp long DNAs of known sequences, we have studied (i) the unusual structure that the phased A-tracts have at temperatures below 37 degrees C, (ii) the thermodynamics of the loss of that aberrant structure well below the duplex melting temperature, and (iii) the conformational changes that occur with temperature. Using temperature-dependent circular dichroism, we detect a low temperature structural transition in a 45-mer duplex with four segments of phased (dA)5 tracks separated by five segments of five randomized G-C pairs, but none in the corresponding isomeric random sequence 45-mer duplex. Differential scanning calorimetry measurements reveal the enthalpy of this preglobal melting transition to be 3.5 kcal/mol.AT pair or 4.4 kcal/mol.AA step. The integrated enthalpy change for this helix-to-helix intramolecular event only is about 16% of the global duplex-to-single-strands melting enthalpy and is relatively broad compared to the global melting event (about 30 vs 15 degrees C for the full width at half maxima). Electric birefringence decay measurements show that the phased 45 bp duplex has a rotational time constant of 100 ns at 5 degrees C which increases to 220 ns above 40 degrees C. Simple modeling of the dynamics within the junction model for bending yields that the bend per A-tract is 42 degrees at 5 degrees C, decreasing to 0 degrees above 40 degrees C. We suggest that this sequence dependent structure which "melts" at physiological temperatures may be relevant to DNA topology and function. PMID- 8218249 TI - Opposite stereoselective resistance to digestion by phosphodiesterases I and II of benzo[a]pyrene diol epoxide-modified oligonucleotide adducts. AB - The deoxyribooligonucleotide 5'-d(CTCACATGTACACTCT) was reacted separately with the chiral diol epoxide isomers 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha- epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE)] and 7 alpha, 8 beta dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene [(-)-anti BPDE)], to produce the modified oligonucleotides 5'-d(CTCACATGBPDETACACTCT). Adducts in which either (+)-anti-BPDE or (-)-anti-BPDE are covalently bound via their C10 positions by trans addition to the exocyclic amino group of the single G residues were isolated and purified by HPLC methods. Snake venom phosphodiesterase (SVPD, phosphodiesterase I), which hydrolyzes DNA from the 3' OH terminus to the 5'-end, digests the (+)-trans-anti-BPDE-oligonucleotide adducts at a significantly faster rate than that of the sterically different (-) trans-anti-BPDE-oligonucleotide adducts. However, using spleen phosphodiesterase (SPD, phosphodiesterase II), which hydrolyzes DNA in the 5'-->3' direction, the opposite stereoselective resistance to digestion is observed. Using shorter BPDE modified oligonucleotides as standards, the enzyme stall sites have been defined by gel electrophoresis methods; the most digestion-resistant phosphodiester linkage is the 5'-d(...T-G*...)-3' bond in the case of (+)-trans-BPDE-modified oligonucleotide adducts for both enzymes, SVPD and SPD (the starred G denotes the site of BPDE modification). In the case of the (-)-trans-BPDE-modified oligonucleotide adducts, the phosphodiester bond on the 3'-side of the modified G [5'-d(...G*-T...)-3'] is most resistant to digestion by both enzymes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218250 TI - Homodinuclear (Pt,Pt) and heterodinuclear (Ru,Pt) metal compounds as DNA-protein cross-linking agents: potential suicide DNA lesions. AB - Homodinuclear (Pt,Pt) and heterodinuclear (Ru,Pt) metal compounds having the generalized formula M(a)NH2(CH)4NH2M(b) are shown to form specific DNA lesions which can efficiently cross-link proteins to DNA. In this study, the homodinuclear case is represented by M(a) = M(b) = [cis-Pt(Cl2)-(NH3)] and the heterodinuclear case is represented by M(a) = [cis-RuCl2(DMSO)3] and M(b) = [cis PtCl2(NH3)]. Native and denaturing polyacrylamide gel electrophoresis was used to show the formation of ternary coordination complexes between the metal-treated 49 bp DNA fragment and the Escherichia coli UvrA and UvrB DNA repair proteins. Treatment with proteinase K results in loss of the DNA-protein cross-links. DNA protein cross-links formed between UvrA and DNA previously modified with the dinuclear metal compounds are reversible with the reducing agent beta mercaptoethanol. The DNA lesion responsible for efficient DNA-protein cross linking is most probably a DNA-DNA interstrand cross-link in which each metal atom is coordinated with one strand of the DNA helix. The formation of DNA repair protein associated DNA cross-links, potential "suicide adducts", suggests a novel action mechanism for these anticancer compounds. In addition, these dinuclear metal compounds should be very useful agents for the investigation of a wide range of protein-DNA interactions. PMID- 8218251 TI - A novel DNA duplex. A parallel-stranded DNA helix with Hoogsteen base pairing. AB - We show here for the first time that a stable parallel double helix with Hoogsteen pairing can exist independently of the triple helix of which it is a component part. The experiments employ DNA oligonucleotides with mixed sequences of normal bases. These duplexes are distinct from previously reported ribopolynucleotide helices containing bulky substituents which prevent Watson Crick pairing as well as from parallel duplexes with Donohue, or reversed Watson Crick, pairing. Stoichiometry is established by mixing curves and gel electrophoresis. Tm depends linearly upon pH, increasing with acidity because of the need to protonate N3 of C. The Tm of the 20-mer studied here is 52 degrees C at pH 5.2 and 0.1 M NaCl. At pH above 6, the molecule rearranges to form an antiparallel duplex with imperfect Watson-Crick pairing and loops, and the Tm is then independent of pH. The CD spectrum of the parallel duplex is very similar to that of the corresponding triple helix but quite different from that of the Watson-Crick helix. The infrared spectrum in the double bond region closely resembles that of the triple helix but, as with the CD, is quite different from that of the Watson-Crick duplex. The infrared spectra of the duplex and triple helix are also nearly identical in the region form 800 to 1000 cm-1, which is sensitive to backbone conformation. The only symmetry element present is a pseudorotational axis coincident with the helix axis of the parallel duplex as well as with the axis of the corresponding triple helix.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218252 TI - NMR strategy for determining Xaa-Pro peptide bond configurations in proteins: mutants of staphylococcal nuclease with altered configuration at proline-117. AB - A general approach has been developed for configurational analysis (cis or trans) of Xaa-Pro peptide bonds in proteins. This approach, which entails selective 13C labeling of Xaa and Pro residues in the protein and isotope-edited NMR, has been applied to mutants of staphylococcal nuclease with suspected altered configurations of the Lys116-Pro117 peptide bond. The technique for monitoring proline configurations is based on differences in interproton distances between the H alpha of residue Xaa and the proline H delta or H alpha protons. Short (< 2.5 A) Xaa H alpha-Pro H delta interproton distances are diagnostic for the trans configuration, whereas short (< 2.5 A) Xaa H alpha-Pro H alpha interproton distances are diagnostic for the cis configuration. Biosynthetic incorporation of [alpha-13C]Xaa and [delta-13C]proline facilitates detection of trans Xaa-Pro peptide bonds, whereas incorporation of [alpha-13C]Xaa and [alpha-13C]proline facilitates detection of cis Xaa-Pro peptide bonds. Provided that the Xaa-Pro peptide bond is unique within the protein sequence, symmetric off-diagonal NOE cross peaks in the isotope-edited NOE spectrum allow for simultaneous chemical shift assignment and determination of the prolyl peptide bond geometry. We have used this technique to determine the predominant configuration of the Lys116 Pro117 peptide bond in recombinant V8 staphylococcal nuclease A (H124L) and two of its single amino acid mutants (D77A+H124L and G79S+H124L). The results are consistent with conclusions reached on the basis of indirect arguments concerning changes in the chemical shifts of histidine 1H epsilon 1 NMR signals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218253 TI - Interaction of thymidylate synthase with pyridoxal 5'-phosphate as studied by UV/visible difference spectroscopy and molecular modeling. AB - Pyridoxal 5'-phosphate (PLP) is an effective inhibitor of Lactobacillus casei thymidylate synthase (TS), competitive with respect to the nucleotide substrate dUMP (Chen et al., 1989). The UV/vis difference spectra of TS-PLP complexes show lambda max at 328 nm due to the specific interaction between Cys 198 of TS and PLP to form a thiohemiacetal, and lambda min at 388 nm due to depletion of free PLP. At high concentrations of PLP a new absorbance at 430 nm forms due to nonspecific Schiff base formation between PLP and lysine residues of the enzyme. Using spectral titration at 328 nm, the binding constant of the specific TS-PLP complex was determined to be 0.5 microM, and the stoichiometry was 2 mol of PLP/mol of TS dimer. The 328-nm absorbance of the TS-PLP complex can be competitively and completely eliminated by addition of dUMP or dTMP; this serves as a convenient binding assay for molecules which bind to the active site of TS. Analogs of PLP which do not contain the phosphate or the aldehyde moieties of PLP bound poorly to the enzyme, thus demonstrating the importance of these functional groups for binding. When treated with PLP, C244T TS, which contains the active site Cys 198 as the sole cysteine residue, showed the same properties as the wild type enzyme. Treatment of the C198A and C198S mutants with PLP did not produce the absorbance at 328 nm assigned to thiohemiacetal formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218254 TI - Crystal structure of ribonuclease Ms (as a ribonuclease T1 homologue) complexed with a guanylyl-3',5'-cytidine analogue. AB - A ribonuclease T1 homologue, ribonuclease Ms (RNase Ms) from Aspergillus saitoi, has been crystallized as a complex with a substrate analogue GfpC where the 2' hydroxyl (2'-OH) group of guanosine in guanylyl-3',5'-cytidine (GpC) is replaced by the 2'-fluorine (2'-F) atom to prevent transesterification. The crystal structure of the complex was solved at 1.8-A resolution to a final R-factor of 0.204. The role of His92 (RNase T1 numbering) as the general acid catalyst was confirmed. Of the two alternative candidates for a general base to abstract a proton from the 2'-OH group, His40 and Glu58 were found close to the 2'-F atom, making the decision between the two groups difficult. We then superposed the active site of the RNase Ms/GfpC complex with that of pancreatic ribonuclease S (RNase S) complexed with a substrate analogue UpcA, a phosphonate analogue of uridylyl-3',5'-adenosine (UpA), and found that His12 and His119 of RNase A almost exactly coincided with Glu58 and His92, respectively, of RNase Ms. Similar superposition with a prokaryotic microbial ribonuclease, RNase St [Nakamura, K. T., Iwahashi, K., Yamamoto, Y., Iitaka, Y., Yoshida, N., & Mitsui, Y. (1982) Nature 299, 564-566], also indicated Glu58 as a general base. Thus the present comparative geometrical studies consistently favor, albeit indirectly, the traditional as well as the most recent notion [Steyaert, J., Hallenga, K., Wyns, L., & Stanssens, P. (1990) Biochemistry 29, 9064-9072] that Glu58, rather than His40, must be the general base catalyst in the intact enzymes of the RNase T1 family. PMID- 8218255 TI - Spectroscopic properties of the states of pig pancreatic phospholipase A2 at interfaces and their possible molecular origin. AB - The near-UV absorption and fluorescence spectroscopic properties of Trp-3 of pig pancreatic phospholipase A2 (PLA2) in aqueous solution (E form) or at the interface without (E* form) or with a ligand at the active site (E*L form) are characterized. In the E form, the single tryptophan residue is exposed on the protein surface to the aqueous environment, as it is freely accessible to aqueous quenchers such as succinimide and acrylamide. The fluorescence quantum yield of E is about one-third that of N-acetyl-tryptophanamide, indicating significant intramolecular quenching processes including charge-transfer reactions, as seen by the D2O effect. Upon binding of PLA2 to micelles of 1-hexadecylpropanediol-3 phosphocholine (E*), a positive difference spectrum with a shoulder at 284 nm (delta epsilon = 370 M-1 cm-1) is observed. Similar difference spectra are also observed upon binding of sulfate ion to the E form. The fluorescence emission of E* is blue-shifted by about 10 nm to 336 nm, with a 2-fold higher quantum yield. Trp-3 in E* is significantly shielded from aqueous quenchers, and the D2O effect on the quantum yield is still present. The UV difference spectrum for the E*-to E*L transition is of large amplitude with peaks at 292 (delta epsilon = 2540 M-1 cm-1) and 284 nm (delta epsilon = 2100 M-1 cm-1), which suggests transfer of tryptophan from an aqueous to a less polar environment. Upon conversion to the E*L form, there is a further blue shift to 333 nm, with about a 20% increase in the fluorescence quantum yield.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218256 TI - Secondary structure analysis of purified functional CHIP28 water channels by CD and FTIR spectroscopy. AB - The integral membrane protein CHIP28 is an important water channel in erythrocytes and kidney tubule epithelia and is a member of a family of channel/pore proteins including the lens protein MIP26. The purposes of this study were to purify functional, delipidated CHIP28 to homogeneity and to determine secondary structure by circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR). CHIP28 was initially purified and delipidated by anion-exchange chromatography following solubilization of N-lauroylsarcosine stripped erythrocyte membranes with beta-octylglucoside (OG); MIP26 was initially purified and delipidated by anion-exchange chromatography following solubilization of urea-stripped bovine lens membranes by monomyristoylphosphatidylcholine. CHIP28 (glycosylated and nonglycosylated) and MIP26 were purified further by high-performance size-exclusion chromatography, eluting in OG as apparent dimers and tetramers, respectively. Proteoliposomes reconstituted with purified CHIP28 were highly water-permeable, with an osmotic water permeability Pf of 0.04 cm/s at 10 degrees C that was inhibited by 0.1 mM HgCl2. Proteoliposomes reconstituted with MIP26 had a low Pf of 0.005 cm/s. CD spectra of CHIP28 in OG or in reconstituted proteoliposomes gave a maximum at 193 nm and minima at 208 and 222 nm. Spectral decomposition using protein basis spectra gave 40 +/- 5% alpha-helix and 43 +/- 3% beta-sheet and -turn. HgCl2 did not affect the CD spectrum of CHIP28. Attenuated total reflectance FTIR of air dried, membrane-associated CHIP28 gave 38 +/- 5% alpha-helix and 40 +/- 4% beta sheet and -turn by spectral decomposition of the amide I resonance. For comparison, CD of MIP26 in OG gave 49 +/- 7% alpha-helix and 32 +/- 12% beta sheet and -turn; FTIR gave 32 +/- 8% alpha-helix and 45 +/- 6% beta-sheet and turn. Analysis of CHIP28 and MIP26 sequence data by the generalized hydropathy method of Jahnig [Jahnig, F. (1990) Trends Biochem. Sci. 15, 93-95] predicted 39 47% alpha-helix and 15-20% beta-structures. These results establish procedures to obtain large quantities of pure CHIP28 and MIP26 in functional forms and provide evidence for multiple membrane-spanning alpha-helices or mixed alpha/beta domains. PMID- 8218257 TI - Nonpolar environment of tryptophans in erythrocyte water channel CHIP28 determined by fluorescence quenching. AB - CHIP28 is an abundant water-transporting protein in erythrocytes, kidney proximal tubule, and other fluid-transporting tissues. To determine the environment of the four tryptophans in CHIP28, fluorescence spectra and quenching by polar and nonpolar compounds were measured in stripped human erythrocyte membranes containing CHIP28 and in proteoliposomes reconstituted with purified CHIP28; comparative studies were performed in membranes containing MIP26. Functional analysis showed that CHIP28 water permeability was not affected by the polar quenchers iodide and acrylamide nor the nonpolar n-anthroyloxy fatty acids (n AF). The emission maximum of CHIP28 tryptophan fluorescence was at 324 +/- 2 nm and did not change with the addition of quenchers; the maximum for MIP26 was at 335 +/- 5 nm. There was weak quenching of CHIP28 tryptophan fluorescence by the polar compounds iodide and acrylamide, with Stern-Volmer constants of 0.13 and 0.71 M-1, respectively. HgCl2 inhibited water permeability by > 95% at 50 microM and quenched CHIP28 fluorescence reversibly by up to 70% with a biphasic concentration dependence; quenching by HgCl2 and acrylamide was not additive. The membrane-associated n-AF probes quenched CHIP28 fluorescence by up to 80% with the greatest quenching for n = 2 and 12; addition of HgCl2 or acrylamide after n AF caused a small, anthroyloxy-position-dependent increase in quenching which was greatest at n = 6. These studies indicate that the tryptophans in CHIP28 are in a nonpolar, membrane-associated environment. Mathematical modeling of the n-AF results suggests that the tryptophans are clustered near the surface and center of the bilayer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218258 TI - The model calmodulin-binding peptide melittin inhibits phosphorylase kinase by interacting with its catalytic center. AB - The inhibition by melittin, a model calmodulin-binding peptide, of phosphorylase kinase, which contains an intrinsic calmodulin subunit, has been characterized in detail. The inhibition was competitive with respect to phosphorylase b for both the phosphorylase kinase holoenzyme and its isolated catalytic gamma-subunit (minus calmodulin), and the ratios of the Km for phosphorylase to the Ki for melittin were similar for both forms of the kinase. These findings indicate that inhibition of the phosphorylase kinase holoenzyme by melittin is caused predominantly by its interaction with the catalytic subunit of the enzyme, and not with the endogenous calmodulin subunit. Further proof that melittin interacts directly with the catalytic site was obtained when it was observed that melittin was also a substrate for phosphorylase kinase, with a Km that was less than that for phosphorylase b, although the kcat/Km specificity constant was only 1/200th of that for phosphorylase. The apparent tight binding of melittin to the kinase active site could not be readily rationalized by conventional comparison of sequence similarity between melittin and phosphorylase; however, considerable sequence similarity, centered around the convertible seryl residue of phosphorylase, was observed when the sequences were aligned in reversed polarity. The possible regulatory significance of the direct interaction of the catalytic site of this Ca(2+)-dependent kinase with a calmodulin-binding peptide is discussed. PMID- 8218259 TI - Actin conformation is drastically altered by direct interaction with membrane lipids: a differential scanning calorimetry study. AB - One of the current dogmas in cytoskeleton research holds that actin filaments are attached to the cell membrane through integral membrane actin-binding proteins. We have challenged this concept, using an in vitro system composed of pure actin and liposomes, and have found that actin may also interact with membrane lipids. Differential scanning calorimetry (DSC) shows that when the actin molecule is in contact with such lipids, it undergoes a major conformational change which results in the complete disappearance of its phase transition. Conversely, DSC scans reveal that the phase transition of the membrane lipids is only weakly affected by the presence of actin. Indeed, the lipids' main transition shows only slight shifts in Tm, from 56.6 to 57 degrees C, and delta Hcal, from 10.1 to 8.8 kcal/mol. In the lipids' pretransition, Tp is shifted from 52.7 to 53.7 degrees C, and delta Hcal is shifted from 0.75 to 0.33 kcal/mol. This interaction between purified actin and membrane lipids is inhibited by high concentrations of KCl, thus indicating that the phenomenon is primarily electrostatic in nature. The ultrastructural consequences of this change in actin conformation were investigated by electron microscopy, which revealed the formation of paracrystalline arrays of actin filaments at the surface of the liposomes. We therefore propose a model in which a limited number of lipid molecules may interact with specific sites on the actin molecule, resulting in the protein's observed conformational change. PMID- 8218260 TI - Acid-induced unfolding and refolding transitions of cytochrome c: a three-state mechanism in H2O and D2O. AB - Whereas the salt-dependent conformational transition of acid-denatured horse ferricytochrome c at pH 2 is approximated by a two-state mechanism from the acid unfolded state to the molten globule state [Kataoka, M., Hagihara, Y., Mihara, K., & Goto, Y. (1993) J. Mol. Biol. 229, 591-596], the corresponding transition in D2O has been proposed to involve a noncompact, alpha-helical intermediate state (the pre-molten globule state) [Jeng, M.-F., & Englander, S. W. (1991) J. Mol. Biol. 221, 1045-1061]. To examine the proposed difference in the conformational transitions, we carried out the HCl and DCl titrations of cytochrome c in H2O and D2O, respectively, measured by far-UV circular dichroism, tryptophan fluorescence, and Soret absorption. In both D2O and H2O, unfolding from the native state to the acid-unfolded state and subsequent refolding to the molten globule state were observed. In either solvent, the conformational transitions were well approximated by a minimal three-state mechanism consisting of the native, molten globule, and acid-unfolded states. Thus, our results did not substantiate the presence of a pre-molten globule state in D2O. Acetylation of amino groups of cytochrome c is known to stabilize the molten globule state at pH 2. On the basis of the three-state mechanism, we constructed a conformational phase diagram for the effect of pH and the degree of acetylation. This phase diagram was similar to that of the pH- and salt-dependent conformational transition of cytochrome c, suggesting that the effects of acetylation on the conformational states are similar to those of salt. PMID- 8218261 TI - Partially folded states of equine lysozyme. Structural characterization and significance for protein folding. AB - Despite their homologous structure, c-type lysozymes and alpha-lactalbumins have been found to differ profoundly in their unfolding behavior, in that the alpha lactalbumins readily enter a partially unfolded collapsed state (the "molten globule"), whereas lysozymes unfold cooperatively to a highly unfolded state. The calcium-binding property of lysozyme from equine milk provides an evolutionary link between the two families of proteins. We demonstrate here that equine lysozyme undergoes a two-stage unfolding transition upon heating or in the presence of guanidine hydrochloride that is highly dependent on the state of calcium binding. Differential scanning calorimetry shows the two transitions to be particularly well resolved in the calcium-free protein, where the first transition occurs with a midpoint at 44 degrees C at pH 4.5 or in 0.8 M GdnHCl at pH 7.5, 25 degrees C, and the second occurs near 70 degrees C at pH 4.5 or in 3.7 M GdnHCl at pH 7.5, 25 degrees C. In the presence of calcium, the first transition takes place with a midpoint of 55 degrees C or in excess of 2.5 M GdnHCl, but the parameters for the second transition remain unchanged. Fluorescence emission and UV difference absorption spectroscopy suggest that the first transition generates an intermediate state in which sequestration of some aromatic side chains from solvent has occurred whereas the second represents denaturation to a highly unfolded state. CD and 1H NMR results indicate that the intermediate state possesses extensive secondary and tertiary structure, although the latter is substantially disordered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218262 TI - Inhibition of protein kinase C by N-myristoylated peptide substrate analogs. AB - Protein kinase C (PKC) is a family of closely related phospholipid-dependent protein kinases. A fully active, phospholipid-independent catalytic fragment of PKC is produced by limited proteolysis of the enzyme. The catalytic fragment allows a simplified assay system for the analysis of PKC inhibitors that interact with the catalytic domain. Recently, we reported that N-myristoylation of the synthetic peptide substrate Arg-Lys-Arg-Thr-Leu-Arg-Arg-Leu (RKRTLRRL) transformed a peptide that completely lacked inhibitory activity against the histone kinase reactions of PKC and its catalytic fragment into a peptide that potently inhibited both of these reactions. N-Myristoylation did not alter the potency of the peptide as a PKC substrate, and the basis for the acquisition of inhibitory activity against the catalytic fragment by N-myristoylation of the peptide remained unclear. In this report, we propose a mechanism for catalytic fragment inhibition by the N-myristoylated peptide that is based on a comparison of the inhibitory potencies of several nonphosphorylatable analogs of N-myristoyl RKRTLRRL, a kinetic analysis of the inhibition of the histone kinase activity of the catalytic fragment by nonphosphorylatable N-myristoyl-RKRTLRRL analogs, and an analysis of the inhibitory effects of the N-myristoylated peptide series on the intrinsic ATPase activity of PKC. Our results support a mechanism in which the N-myristoylated peptides inhibit the catalytic fragment by binding to PKCfree, but not to the complex PKC-ATP, at the protein-substrate binding site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218263 TI - Immediate reduction of cytochrome c by photoexcited NADH: reaction mechanism as revealed by flow-flash and rapid-scan studies. AB - Upon exposure of an aqueous solution of NADH and cytochrome c to a laser pulse at 355 nm under anaerobic conditions, cytochrome c is reduced within 1-2 ms to a maximal extent of 90%. The reduction proceeds in two phases: rapid reduction by hydrated electrons followed by bimolecular electron transfer from the NAD radical to ferric cytochrome c. In addition, a third reduction phase emerges in the presence of an appropriate concentration of molecular oxygen, where the superoxide anion is a reductant. As the oxygen concentration approaches 20% saturation, the cytochrome c reduction by NAD is abolished first and then the reduction by hydrated electrons, since molecular oxygen competes with cytochrome c for NAD and hydrated electrons. At 20% oxygen, cytochrome c is reduced almost exclusively by the superoxide anion, but the amount reduced on a single laser pulse is only one-fourth that reduced under anaerobic conditions. The second order rate constants for the reduction of cytochrome c at pH 7.4 and 20 degrees C by NAD and the superoxide anion are 2.0 x 10(9) and 4.0 x 10(6) M-1 s-1, respectively. PMID- 8218264 TI - Lateral diffusion of an integral membrane protein: Monte Carlo analysis of the migration of phosphorylated light-harvesting complex II in the thylakoid membrane. AB - The lateral migration of the integral light-harvesting chlorophyll a/b protein complex of photosystem II, LHCII, has been studied in the undisturbed membranes of thylakoids without artificial probes. LHCII was phosphorylated at 0 degree C. The diffusion of the mobile phospho-LHCII from appressed grana to nonappressed membrane regions was induced by a temperature jump to 20 degrees C and analyzed by a rapid detergent fractionation of the two membrane areas. This long-range diffusion of the integral phospho-LHCII is analyzed by a Monte Carlo calculation which is based on a model of the thylakoid membrane and includes all integral proteins as mobile particles. A comparison of the calculation with the experimental time course indicates a diffusion constant of phospho-LHCII in the range of (2-4) x 10(-12) cm2 s-1. This value is evidence for a severe restriction of protein mobility in the appressed thylakoid membrane. From a statical point of view, the percolation theory predicts that the high protein density in the grana membranes is above the threshold of percolation and the long-range diffusion should be inhibited by finite clusters of lipids. However, the shape of the experimental time course is in favor of a lateral motion also of photosystem II and nonphosphorylated LHCII and not of a rigid lattice of these complexes. Our data and Monte Carlo analysis suggest a dynamic or fluid lattice of the protein complexes with a lifetime of the clusters in the millisecond time range. The consequences of these transient fluctuations on the long-range diffusion of plastoquinone are discussed. PMID- 8218266 TI - EPR and ENDOR detection of compound I from Micrococcus lysodeikticus catalase. AB - We present the first EPR and ENDOR examination of a catalase compound I (Cat I), the one formed by peracetic acid treatment of Micrococcus lysodeikticus catalase. The Cat I rapid-passage EPR signal (g perpendicular eff = 3.32; g parallel eff approximately 2) appears quite different from those reported previously for the compounds I from horseradish peroxidase (HRP I) and chloroperoxidase. Nonetheless, all three signals can be explained by the same model for exchange coupling between an S = 1 oxoferryl [Fe = O]2+ moiety and a porphyrin pi-cation radical (S' = 1/2) (Schulz, C. E., et al. (1979) FEBS Lett. 103, 102-105). The signal for Cat I is unlike those for the two peroxidases in that it reflects a ferromagnetic rather than antiferromagnetic exchange. Preliminary 1H ENDOR spectra for Cat I appear to differ from the proton (1H) ENDOR spectra of HRP I; the latter, along with the 14N ENDOR spectra, indicate that the porphyrin radical in HRP I exhibits a predominantly A2u-like state having large spin densities on porphyrin N and C(beta). The proton ENDOR spectrum of Cat I is insensitive to H/D exchange, which indicates that the [Fe = O]2+ moiety is not protonated. Consideration of the EPR results for a series of compounds I suggests that the sign and magnitude of the exchange parameter (J) is correlated with the nature of the proximal axial ligand. PMID- 8218265 TI - Functional expression in Escherichia coli of the mitotic regulator proteins p24ran and p45rcc1 and fluorescence measurements of their interaction. AB - The gene products for the mitotic regulator genes RCC1 and Ran, p45rcc1 and p24ran, were expressed in Escherichia coli, purified in large amounts, and characterized for their biochemical properties. p24ran binds guanine nucleotide as a 1:1 complex, which is only slowly released from the protein. p45rcc1 catalyzes the exchange of nucleotide bound to the guanine nucleotide binding protein p24ran in the same way as the protein purified from HeLa cells. Likewise, the nucleotide dissociation from HeLa cell-derived p24ran protein is equally efficient with recombinant and nonrecombinant proteins. The recombinant proteins form a strong complex which contains no bound nucleotide. The kinetics of nucleotide exchange on p24ran in the presence or absence of p45rcc1 can be conveniently monitored either by the direct tryptophan fluorescence of p24ran or by fluorescence energy transfer measurements involving fluorescent nucleotides. PMID- 8218267 TI - Cofactor characterization and mechanistic studies of CDP-6-deoxy-delta 3,4 glucoseen reductase: exploration into a novel enzymatic C-O bond cleavage event. AB - The CDP-6-deoxy-delta 3,4-glucoseen reductase (E3) is a NADH-dependent enzyme which catalyzes the key reduction of the C-3 deoxygenation step during the formation of CDP-ascarylose, a 3,6-dideoxyhexose found in the lipopolysaccharide of Yersinia pseudotuberculosis. This highly purified enzyme is also a NADH oxidase capable of mediating the direct electron transfer from NADH to O2, forming H2O2. While previous work showed that E3 contains no common cofactor, one FAD and one plant ferredoxin type [2Fe-2S] center were found in this study to be associated with each molecule of E3. The iron-sulfur center is essential for E3 activity since bleaching of the [2Fe-2S] center leads to inactive enzyme. These results suggest that E3 employs a short electron-transport chain composed of both FAD and the iron-sulfur center to shuttle electrons from NADH to its acceptor. The order of electron flow, as indicated by EPR measurement with partially reduced E3, starts with hydride reduction of FAD by NADH. The iron-sulfur cluster, receiving electrons one at a time from the reduced flavin, relays the reducing equivalents via another iron-sulfur center in the active site of E1 to its final acceptor, the E1-bound PMP-glucoseen adduct. The participation of a one electron-carrying iron-sulfur center in this reduction is advantageous since both electrons are dispatched from the same redox state of the prosthetic group, allowing electrons of equal energy to be delivered to the final acceptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218268 TI - Understanding the rates of certain enzyme-catalyzed reactions: proton abstraction from carbon acids, acyl-transfer reactions, and displacement reactions of phosphodiesters. AB - The structural factors responsible for the rapid rates (kcats) of enzyme catalyzed reactions are not well understood. In this paper, we outline an analysis that we believe can provide a quantitative understanding of the kcats of three types of reactions: abstraction of the alpha-protons from carbon acids, acyl-transfer reactions, and displacement reactions of phosphodiesters. We propose that these reactions proceed via the formation of intermediates in which negative charge develops on the carbonyl or phosphoryl oxygens. Our analysis is based on Marcus formalism that separates the activation energy barrier for conversion of bound substrate to the intermediate, delta G++, into contributions from a thermodynamic barrier, delta G zero, and an intrinsic kinetic barrier, delta G++int. We propose that one (or more) general acid catalyst positioned adjacent to the carbonyl or phosphoryl oxygens of the substrate is primarily responsible for reducing both delta G zero and delta G++int from the values that characterize nonenzymatic reactions. The proton donors (1) stabilize the intermediates via the formation of short, strong hydrogen bonds (the pKas of the protonated intermediates and the general acid catalysts are matched), thereby reducing delta G zero, and (2) stabilize the transition states for formation of the intermediates by negating the developing charge on the oxygens without the requirement for significant structural reorganization, thereby reducing delta G++int. The possible reductions in delta G zero and delta G++int are sufficient to understand the rapid kcats of these reactions. PMID- 8218269 TI - The gateway to the active site of heme-copper oxidases. AB - The spectroscopy and dynamics of CO binding were measured for wild-type and mutant cytochromes bo, members of the superfamily of heme-copper oxidases. The results suggest that access of ligands, including substrate O2, to the binuclear Fe-Cu active site is controlled at two levels. CO recombination to the wild-type ubiquinol oxidase exhibited saturation kinetics (kmax = 190 s-1, Km = 2.4 mM), indicative of the existence of an intermediate in the ligand-binding pathway. FTIR spectroscopy and TRIR spectroscopy were used to demonstrate conclusively that this intermediate was a CuB-CO complex. Two mutant oxidases (His333Leu, His334Leu) which lack CuB showed no evidence of saturation of CO rebinding, even up to 21 mM CO. Also, the absolute rates of CO binding to the mutant oxidases were much greater than for wild type, even at CO concentrations well below the apparent Km for wild-type enzyme. These results clearly indicate that the copper ion at the binuclear site acts as an obligatory way station, or gate, severely limiting the approach of ligands to the heme active site. Further, an analysis of the rate constants for CO binding to CuB suggests that the protein structure external to the binuclear site regulates ligand entry into this site. We propose that these control mechanisms for substrate binding are operative throughout this general class of enzymes. PMID- 8218271 TI - Structural evidence for a pH-sensitive dilysine trigger in the hen ovotransferrin N-lobe: implications for transferrin iron release. AB - Members of the transferrin family of proteins are involved in Fe3+ transport (serum transferrins) and are also believed to possess antimicrobial activity (ovotransferrins and lactoferrins). The structure of the monoferric N-terminal half-molecule of hen ovotransferrin, reported here at 2.3-A resolution, reveals an unusual interdomain interaction formed between the side-chain NZ atoms of Lys 209 and Lys 301, which are 2.3 A apart. This strong interaction appears to be an example of a low-barrier hydrogen bond between the two lysine NZ atoms, both of which are also involved in a hydrogen-bonding interaction with the aromatic ring of a tyrosine residue. Crystals of the protein were grown at pH 5.9, which is well below the usual pKa approximately 10 for a lysine side chain. We suggest that the pKa of either one or both of these residues lies below the pH of the structure determination and is, therefore, not positively charged. This finding may serve to explain, on a molecular basis, the pH dependence of transferrin Fe3+ release. We propose that uptake of the Fe(3+)-transferrin complex into an acidic endosome (viz., pH approximately 5.0) via receptor-mediated endocytosis will result in the protonation of both lysine residues. The close proximity of the two resulting positive charges, and their location on opposite domains of the N-lobe, might well be the driving force that opens the two domains of the protein, exposing the Fe3+ ion and facilitating its release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218270 TI - Increasing sequence length favors alpha-helix over 3(10)-helix in alanine-based peptides: evidence for a length-dependent structural transition. AB - Ala-based peptides form marginally stable helices at low temperature and are conventionally considered as mixtures of alpha-helix and random coil. However, recent work with doubly spin-labeled peptides suggests that short 16-residue sequences contain a significant fraction of 3(10)-helix near the N-terminus (positions 4-8). Using the same double-label strategy, we report on the helix geometry of the peptides Ac-(AAAAK)nA-NH2 with n = 3 and n = 4. The 16-mer (n = 3) is now examined at a region near the C-terminus, and there is evidence for 3(10)-helix here as well. The 21-mer (n = 4) is examined in three regions of the sequence. In dramatic contrast to the 16-mer, the 21-mer exhibits the signature of alpha-helix at the N-terminus and on through the middle of the peptide. The 21 mer C-terminus, however, adopts the 3(10)-helix geometry as is often found for C termini in protein alpha-helices. These data indicate that the proportion of alpha-helix and 3(10)-helix in Ala-based peptides depends upon the sequence length. PMID- 8218272 TI - Solution structure of P05-NH2, a scorpion toxin analog with high affinity for the apamin-sensitive potassium channel. 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. P05, a 31-residue polypeptide cross-linked by three disulfide bridges, also possesses binding and physiological properties similar to those of the bee venom toxin apamin (18 residues, two disulfides). However, the amino acid sequences of these two polypeptides are dissimilar, except for a common Arg-Arg Cys-Gln motif which is located on an alpha-helix. P05-NH2, a synthetic analog of P05, unlike native P05, was found to bind irreversibly to the apamin receptor. The solution structure of P05-NH2 has been solved by conventional two-dimensional NMR techniques followed by distance geometry and energy minimization. The obtained conformation is composed of two and an half turns of alpha-helix (residues 5-14) connected by a tight turn to a two-stranded antiparallel beta sheet (sequences 17-22 and 25-29). This beta-sheet has a right-handed twist as usual for such secondary structures. The beta-turn connecting the two strands belongs to type II'. This structure is homologous to all scorpion toxin structures known so far as well as to insect defensins. The three arginines known to be involved in the pharmacological activity, i.e., Arg6, Arg7, and Arg13, are all located on the solvent-exposed side of the helix and form a positively charged surface which includes Gln9. The calculated electrostatic potential is highly asymmetric with the greatest positive potential centered on the Arg-rich alpha-helix side.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218273 TI - Molecular structure of kanamycin nucleotidyltransferase determined to 3.0-A resolution. AB - Kanamycin nucleotidyltransferase, as originally isolated from Staphylococcus aureus, inactivates the antibiotic kanamycin by catalyzing the transfer of a nucleotidyl group from nucleoside triphosphates such as ATP to the 4'-hydroxyl group of the aminoglycoside. The molecular structure of the enzyme described here was determined by X-ray crystallographic analysis to a resolution of 3.0 A. Crystals employed in the investigation belonged to the space group P4(3)2(1)2 with unit cell dimensions of a = b = 78.9 A and c = 219.2 A. An electron density map phased with seven heavy-atom derivatives revealed that the molecules packed in the crystalline lattice as dimers exhibiting local 2-fold rotation axes. Subsequent symmetry averaging and solvent flattening improved the quality of the electron density such that it was possible to completely trace the 253 amino acid polypeptide chain. Each monomer is divided into two distinct structural domains: the N-terminal motif composed of residues Met 1-Glu 127 and the C-terminal half delineated by residues Ala 128-Phe 253. The N-terminal region is characterized by a five-stranded mixed beta-pleated sheet whereas the C-terminal domain contains five alpha-helices, four of which form an up-and-down alpha-helical bundle very similar to that observed in cytochrome c'. The two subunits wrap about one another to form an ellipsoid with a pronounced cleft that could easily accommodate the various aminoglycosides known to bind to the enzyme. PMID- 8218274 TI - Protein response to photodissociation of CO from carbonmonoxymyoglobin probed by time-resolved infrared spectroscopy of the amide I band. AB - Protein conformational changes coupled to the ligation reactions of carbon monoxide in myoglobin (Mb) are detected by time-resolved infrared spectroscopy. An apparatus based on a tunable diode laser operating in the region of 1650 cm-1 is used to probe changes in the amide I absorption band of the protein in response to photodissociation and subsequent rebinding of CO. The time course of changes in the amide I band is shown to follow the recombination of photolyzed CO with Mb. A time-resolved difference spectrum in the amide I region is generated by tuning the diode laser probe source. The features in the IR difference spectrum are assigned to the motions of the polypeptide backbone associated with the global relaxation of the protein from the ligated to the deoxy conformation. A static difference spectrum generated by subtracting FTIR spectra of carbonmonoxy-Mb and deoxy-Mb is essentially identical to the transient spectrum, indicating that the protein relaxation is complete with the 100-ns time resolution of the experiment. PMID- 8218275 TI - Kinetic characterization of the ATPase activity of the DNA packaging enzyme from bacteriophage lambda. AB - Terminases are enzymes common to all of the complex double-stranded DNA viruses and are required for viral assembly. These enzymes function to excise a single viral genome from a concatemeric DNA precursor and package it into a preformed protective protein shell or capsid. ATP hydrolysis by these enzymes has been described and appears to be critical to the packaging process. We have previously characterized the endonuclease activity of purified terminase from bacteriophage lambda [Tomka, M. A., & Catalano, C. E. (1993) J. Biol. Chem. 268, 3056-3065], and we describe here a kinetic characterization of the ATPase activity of the enzyme. lambda Terminase possesses a DNA-stimulated ATPase activity and hydrolyzes ATP to ADP and Pi. This activity requires divalent metal and is supported by all of the group IIa metals examined, as well as Mn2+. The reaction is also stimulated by NaCl, GTP, and dGTP. Of note is that neither of the guanosine nucleotides is hydrolyzed by the enzyme, while dATP is hydrolyzed at a rate comparable to that of ATP. Kinetic analysis of the ATPase activity revealed two apparent binding sites for ATP hydrolysis. The high-affinity site (Km = 5 microM) and low-affinity site (Km approximately 1.3 mM) hydrolyze ATP with kcat = 3 and 16 min-1, respectively. While the high-affinity site is unaffected by the presence of DNA, ATP hydrolysis at the low-affinity site is stimulated by DNA, which results from both a decrease in the Km and a concomitant increase in the kcat of the reaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218276 TI - Mechanism of inactivation of human O6-alkylguanine-DNA alkyltransferase by O6 benzylguanine. AB - Human O6-alkylguanine-DNA alkyltransferase was rapidly inactivated by low concentrations of O6-benzylguanine, but the alkyltransferase from the Escherichia coli ogt gene was much less sensitive and alkyltransferases from the E. coli ada gene or from yeast were not affected. O6-Benzyl-2'-deoxyguanosine was less potent than the base, but was still an effective inactivator of the human alkyltransferase and had no effect on the microbial proteins. O6-Allylguanine was somewhat less active, but still gave complete inactivation of both the human and Ogt alkyltransferases at 200 microM in 30 min, slightly affected the Ada protein, and had no effect on the yeast alkyltransferase. O4-Benzylthymidine did not inactivate any of the alkyltransferase proteins tested. Inactivation of the human alkyltransferase by O6-benzylguanine led to the formation of S-benzylcysteine in the protein and to the stoichiometric production of guanine. The rate of guanine formation followed second-order kinetics (k = 600 M-1 s-1). Prior inactivation of the alkyltransferase by reaction with a methylated DNA substrate abolished its ability to convert O6-benzylguanine into guanine. These results indicate that O6 benzylguanine inactivates the protein by acting as a substrate for alkyl transfer and by forming S-benzylcysteine at the acceptor site of the protein. The inability of O6-benzylguanine to inactivate the microbial alkyltransferases may be explained by steric constraints at this site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218277 TI - Use of aromatase (CYP19) metabolite ratios to characterize electron transfer from NADPH-cytochrome P450 reductase. AB - Aromatase catalyzes the conversion of 4-androstene-3,17-dione to estrogen with the concomitant formation of the minor metabolites 4-androstene-19-hydroxy-3,17 dione(19-hydroxyandrostenedione) and 4-androstene-3,17,19-trione(19 oxoandrostenedione). Microsomes of chinese hamster ovary (CHO) cells expressing human aromatase were isolated to investigate androstenedione metabolism. Relatively greater amounts of the minor metabolites result after limitation of electron flux from NADPH-cytochrome P450 reductase to aromatase. Substitution of NADH for NADPH or limitation of NADPH availability increased minor metabolite formation relative to estrogen formation. Similar changes in metabolite ratios were observed when metabolism was conducted either at high pH (8.3) or in the presence of n-alcohols in the range of 5-200 mM alcohol concentrations. However, conditions of low pH (5.5) or high ionic strength (1 M KCl) resulted in minor changes in metabolite ratios, suggesting little or no effect on electron flux between NADPH-cytochrome P450 reductase and aromatase. Theoretical molar ratios of the resulting metabolites were predicted using a reaction scheme assuming sequential substrate oxidations without reversible intermediate release from the aromatase active site. This model was supported by a close agreement between theoretical and experimental metabolite ratios for a broad range of NADPH concentrations. The results indicate that metabolite ratios provide a sensitive indicator of aromatase-oxidoreductase interactions in the microsomal environment. PMID- 8218278 TI - Photodissociation and recombination of carbonmonoxy cytochrome oxidase: dynamics from picoseconds to kiloseconds. AB - The kinetics of the flash-induced photodissociation and rebinding of carbon monoxide in cytochrome aa3-CO have been studied by time-resolved infrared (TRIR) and transient ultraviolet-visible (UV-vis) spectroscopy at room temperature and by Fourier transform infrared (FTIR) spectroscopy at low temperature. The binding of photodissociated CO to CuB+ at room temperature is conclusively established by the TRIR absorption at 2061 cm-1 due to the C-O stretching mode of the CuB(+)-CO complex. These measurements yield a first-order rate constant of (4.7 +/- 0.6) x 10(5) s-1 (t1/2 = 1.5 +/- 0.2 microseconds) for the dissociation of CO from the CuB(+)-CO complex into solution. The rate of rebinding of flash-photodissociated CO to cytochrome a(3)2+ exhibits saturation kinetics at [CO] > 1 mM due to a preequilibrium between CO in solution and the CuB(+)-CO complex (K1 = 87 M-1), followed by transfer of CO to cytochrome a(3)2+ (k2 = 1030 s-1). The CO transfer from CuB to Fe alpha 3 was followed by CO-FTIR between 158 and 179 K and by UV vis at room temperature. The activation parameters over the temperature range 140 300 K are delta H++ = 10.0 kcal mol-1 and delta S++ = -12.0 cal mol-1 K-1. The value of delta H++ is temperature independent over this range; i.e., delta Cp++ = 0 for CO transfer. Rapid events following photodissociation and preceding rebinding of CO to cytochrome a(3)2+ were observed. An increase in the alpha-band of cytochrome a3 near 615 nm (t1/2 ca. 6 ps) follows the initial femtosecond time scale events accompanying photodissociation. Subsequently, a decrease is observed in the alpha-band absorbance (t1/2 approximately 1 microsecond) to a value typical of unliganded cytochrome a3. This latter absorbance change appears to occur simultaneously with the loss of CO by CuB+. We ascribe these observations to structural changes at the cytochrome a3 induced by the formation and dissociation of the CuB(+)-CO complex. We suggest that the picosecond binding of photodissociated CO to CuB triggers the release of a ligand L from CuB. We infer that L then binds to cytochrome a3 on the distal side and that this process is directly responsible for the observed alpha-band absorbance changes. We have previously suggested that the transfer of L produces a transient five-coordinate high-spin cytochrome a3 species where the proximal histidine has been replaced by L. When CO binds to the enzyme from solution, these processes are reversed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8218279 TI - Formation of the meta II photointermediate is accompanied by conformational changes in the cytoplasmic surface of rhodopsin. AB - Five mutations of rhodopsin have been produced, each of which contains a unique cysteine residue at positions 62, 65, 140, 240, or 316 in the cytoplasmic domain. The single reactive cysteines were derivatized with a sulfhydryl-specific nitroxide spin-label, and the electron paramagnetic resonance (EPR) spectra were analyzed in both lauryl maltoside and digitonin in the dark and after photobleaching. The collision rate of the attached nitroxides with polar and nonpolar paramagnetic agents indicated that they were all exposed to the aqueous environment. Photobleaching of the mutants in digitonin, which arrests the protein at the meta I intermediate, produced little change in mobility of the attached nitroxide. On the other hand, photobleaching in lauryl maltoside produced the meta II intermediate and significant changes in the EPR spectra of the nitroxides attached to positions 140 and 316. These data directly reveal a light-induced conformational change in the cytoplasmic loops that accompanies meta II formation. PMID- 8218280 TI - Water structural changes in lumirhodopsin, metarhodopsin I, and metarhodopsin II upon photolysis of bovine rhodopsin: analysis by Fourier transform infrared spectroscopy. AB - Difference Fourier transform infrared spectra of lumirhodopsin, metarhodopsin I, and metarhodopsin II versus rhodopsin were recorded with hydrated films of bovine rod outer segments at 200, 240, and 270 K. In the region between 3700 and 3450 cm 1, the O-H stretching vibrational bands of water were identified by H(2)18O and 2H2O shifts. Lumirhodopsin and metarhodopsin I exhibit almost identical spectral shape in this region. The O-H stretching vibration band of water was detected at 3533 cm-1 upon formation of lumirhodopsin and metarhodopsin I and at 3641 cm-1 upon formation of metarhodopsin II. The results suggest that hydrogen bonding of water molecules in the protein is stronger in lumirhodopsin and metarhodopsin I, intermediates with a protonated Schiff base, than in metarhodopsin II with an unprotonated Schiff base. This is similar to the case of photoreaction of bacteriorhodopsin, in which stronger hydrogen bonding of water is formed in the L intermediate than the M intermediate [Maeda, A., Sasaki, J., Shichida, Y., & Yoshizawa, T. (1992) Biochemistry 31, 462-467]. PMID- 8218281 TI - Fluorescent-labeled growth factor molecules serve as probes for receptor binding and endocytosis. AB - In this report, we describe the applicability of fluorescein-labeled EGF (FITC EGF) in monitoring the interaction between EGF and its cellular receptor in real time. This work takes advantage of previous studies that demonstrated that EGF may be labeled at its amino terminus with FITC without significant deleterious effects on the binding of the growth factor to its receptor or on the ability of the growth factor to activate the intrinsic tyrosine kinase activity of the receptor. When suspended human epidermoid carcinoma (A431) cells were treated with FITC-EGF, a biphasic quenching of the FITC fluorescence was observed. Both phases were blocked when the experiments were performed in the presence of excess unlabeled EGF. The first phase, in which the FITC emission was quenched by 8-10%, was complete within 30 s. This rapid quenching was attributed to changes in the rotational mobility of the EGF molecule that accompany its binding to receptors. The slower phase required 20-30 min for completion and resulted in the further quenching of the FITC fluorescence by 30-40%. This slower phase appeared to reflect the internalization of the receptor and its routing to acidic intracellular compartments. The rapid fluorescence decay phase was used to determine the rate constants (k(on) and k-off)) for the interaction of FITC-EGF with receptors on the surface of cells. PMID- 8218282 TI - Two different rigor complexes of myosin subfragment 1 and actin. AB - Our previous titration and cross-linking experiments showed that myosin subfragment 1 (S1) can bind to one or two monomers in F-actin [Andreev, O. A., & Borejdo, J. (1991) Biochem. Biophys. Res. Commun. 177, 350-356; (1992a) J. Muscle Res. Cell Motil. 13, 523-533; (1992b) Biochem. Biophys. Res. Commun. 188, 94 101]. In the present work we used a sedimentation method to extend these studies to equilibrium binding and a stopped flow method to investigate its kinetics. Both equilibrium and kinetic data indicated the existence of two different rigor complexes. On the basis of these data we developed a model which suggested that binding of S1 to F-actin occurred in two steps: (i) initial rapid binding to one monomer of F-actin, A + M<==>A.M and (ii) a consequent slow binding to a neighboring monomer, A.M + A<==>A.M.A, where A stands for actin and M for myosin subfragment 1. The second reaction can proceed only if the neighboring actin site is unoccupied. The model fit the equilibrium and kinetic binding data with equilibrium constants K1 = 6 x 10(6) M-1 and K2 = 4 and kinetic constants k+1 = 10.5 x 10(6) M-1 s-1, k-1 = 1.75 s-1, k+2 = 0.8 s-1, and k-2 = 0.2 s-1, where the subscripts refer to the reactions i and ii. These results corroborate our hypothesis that myosin head can make two types of complexes with F-actin and support our speculation that during a power stroke in contracting muscle a myosin head may first bind to one and then to two actins. PMID- 8218283 TI - Boundary of the autoinhibitory region of smooth muscle myosin light-chain kinase. AB - It has been proposed that myosin light-chain kinase (MLCK) activity is inhibited in the absence of Ca2+/calmodulin by a pseudosubstrate sequence [Kemp, B. E., Pearson, R. B., Guerriero, V. J., Bagchi, I., & Means, A. R. (1987) J. Biol. Chem. 262, 2542-2548]. To evaluate this hypothesis, the role of a cluster of basic residues, Arg797-Arg798-Lys799, which are essential for the pseudosubstrate sequence, in the inhibition of MLCK was studied. A full-length cDNA of chicken gizzard MLCK was obtained, and the recombinant MLCK which contains the entire amino acid sequence was expressed in Escherichia coli. The Ca2+/calmodulin dependent activity of the recombinant MLCK was comparable to that of the naturally isolated MLCK. Two truncation mutants, MT799 and MT796, were produced, of which MT799 but not MT796 contained a cluster of basic residues. Neither MT799 nor MT796 bound calmodulin, and kinase activity was inhibited (similar to MLCK activity in the absence of Ca2+/calmodulin). However, the kinase activity of the mutants was increased markedly by subsequent tryptic proteolysis. The tryptic digestion of the mutants initially produced a 64-kDa fragment then, subsequently, the 61-kDa fragment, and the increase in activity coincided with the appearance of the 61-kDa fragment. This was similar to the digestion profile of native MLCK, and it is known that the 61-kDa fragment is the constitutively active kinase [Ikebe, M., Stepinska, M., Kemp, B. E., Means, A. R., & Hartshorne, D. J. (1987) J. Biol. Chem. 262, 13828-13834].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218284 TI - Functional identification and quantitation of three intracellular calcium pools in GH4C1 cells: evidence that the caffeine-responsive pool is coupled to a thapsigargin-resistant, ATP-dependent process. AB - We have recently reported that basal oscillations in cytosolic free Ca2+ concentration ([Ca2+]i) in intact GH4C1 cells are dependent on a Ca(2+)-induced Ca2+ release (CICR) mechanism. The purpose of the present study was to characterize the uptake and release pathways for intracellular Ca2+ in GH4C1 cells. We have used both permeabilized cells and microsome preparations, and we have monitored the change in ambient [Ca2+] using the dye, fluo 3. We find that there are three functionally distinct nonmitochondrial, ATP-dependent Ca2+ pools in these cells: Pool 1 is an inositol 1,4,5-trisphosphate (InsP3) responsive pool which is filled by a thapsigargin (Tg) sensitive Ca(2+)-ATPase; pool 2 is a second Tg-sensitive pool which is InsP3-unresponsive; and pool 3 is a Tg resistant pool, at least a part of which has the characteristics of a CICR mechanism. These pools were established as follows. Tg caused additional Ca2+ release after maximum release was induced by prior addition of InsP3. In contrast, the InsP3 response was abolished in a time-dependent manner after pretreatment with Tg. Ambient Ca2+, added after maximum blockade by Tg, was still able to be sequestered. Ionomycin released Ca2+ even after maximum depletion by Tg. The ionomycin-releasable pool remaining after Tg treatment was also ATP dependent, because this pool was completely discharged by ATP-depletion. Two additional inhibitors of intracellular Ca(2+)-ATPases, 2,4-di(tert butyl)hydroquinone and cyclopiazonic acid, which are structurally unrelated to Tg, acted on the same targets as Tg. To estimate accurately the distribution of Ca2+ among compartments, we developed a new approach based on the analysis of two equilibrium states of Ca2+ distribution. Using this method, the size of the Tg sensitive pools (pools 1 + 2) was estimated to be 63 +/- 2.5% of total non mitochondrial Ca2+ in our preparation. Caffeine induced Ca2+ release, and this action was observed even after complete depletion of the Tg-sensitive pool, indicating that pool 3 had the characteristics of a CICR compartment. Because caffeine pretreatment caused an increase in the size of pools 1 + 2, the CICR like mechanism operated primarily on pool 3. These new results strengthen our model, in which a distinct CICR-like pool is responsible for Ca2+ oscillations in GH4C1 cells, and also support the concept that different types of Ca2+ efflux pathways occur in Ca(2+)-storing nonmitochondrial organelles containing different types of Ca(2+)-ATPases. PMID- 8218285 TI - Three distinct domains in the cholinesterase molecule confer selectivity for acetyl- and butyrylcholinesterase inhibitors. AB - By examining inhibitor interactions with single and multiple site-specific mutants of mouse acetylcholinesterase, we have identified three distinct domains in the cholinesterase structure that are responsible for conferring selectivity for acetyl- and butyrylcholinesterase inhibitors. The first domain is the most obvious; it defines the constraints on the acyl pocket dimensions where the side chains of F295 and F297 primarily outline this region in acetylcholinesterase. Replacement of these phenylalanine side chains with the aliphatic residues found in butyrylcholinesterase allows for the catalysis of larger substrates and accommodates butyrylcholinesterase-selective alkyl phosphates such as isoOMPA. Also, elements of substrate activation characteristic of butyrylcholinesterase are evident in the F297I mutant. Substitution of tyrosines for F295 and F297 further alters the catalytic constants. The second domain is found near the lip of the active center gorge defined by two tyrosines, Y72 and Y124, and by W286; this region appears to be critical for the selectivity of bisquaternary inhibitors, such as BW284C51. The third domain defines the site of choline binding. Herein, in addition to conserved E202 and W86, a critical tyrosine, Y337, found only in the acetylcholinesterases is responsible for sterically occluding the binding site for substituted tricyclic inhibitors such as ethopropazine. Analysis of a series of substituted acridines and phenothiazines defines the groups on the ligand and amino acid side chains in this site governing binding selectivity. Each of the three domains is defined by a cluster of aromatic residues. The two domains stabilizing the quaternary ammonium moieties each contain a negative charge, which contributes to the stabilization energy of the respective complexes. PMID- 8218286 TI - Cholesterol transport function of pancreatic cholesterol esterase: directed sterol uptake and esterification in enterocytes. AB - We have recently hypothesized that neutral lipids can, in part, move across biological membranes via a mechanism involving enzymes anchored to membrane proteoglycans such as those found in the brush border of the enterocyte [Bosner, M. S., Gulick, T., Riley, D. J. S., Spilburg, C. A., & Lange, L. G. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7438-7442]. Present results now show a subsequent, essential protein-mediated sorting of neutral lipids for further intracellular metabolism. Thus, in the absence of enzyme, 0.002 pmol of cellular ester appeared after 2 h, and its level increased only 3.5-fold after 12 h. However, in the presence of cholesterol esterase, the level of cholesterol ester increased 39 fold in the same time period, indicating that the enzyme-mediated uptake accounts for 10-fold greater ester synthesis than that from basal absorption. Kinetic analysis reveals that both enzyme-mediated and background absorption depend on taurocholate concentration and are second-order reactions more likely dependent on collision than diffusion. Other lipid-recognizing proteins such as pancreatic triglyceride lipase and the intestinal fatty acid binding protein are not stimulatory to intracellular cholesterol processing. Taken together, these data suggest that pancreatic cholesterol esterase and possibly other proteoglycan binding extracellular enzymes of neutral lipid metabolism may facilitate movement of neutral lipids into the plasma membrane and direct them into functional intracellular sites. PMID- 8218287 TI - Excitation energy transfer in DNA: duplex melting and transfer from normal bases to 2-aminopurine. AB - Absorption and fluorescence excitation and emission spectra of the B DNA duplex decamer d[CTGA(2AP)TTCAG]2, where emission from the 2AP (2-aminopurine) base dominates, have been measured as a function of temperature. A low-temperature excitation band in the 260-270-nm region disappears near the duplex melting temperature, Tm = 27 degrees C, but then reappears at higher temperatures. Singlet-singlet energy transfer thus occurs between the normal DNA bases and the 2AP base in the B-helical conformation and to a lesser extent in the structurally mobile melted conformation. The measured efficiency of transfer is 4-5% at 4 degrees C, near 0 at 30 degrees C, and rises again to 1% at 48 degrees C. Nearest neighbor-only singlet transfer is likely. Such transfer does not offer a likely explanation for UV damage distributions in DNA. PMID- 8218288 TI - Preferential binding of the xeroderma pigmentosum group A complementing protein to damaged DNA. AB - The xeroderma pigmentosum group A complementing protein (XPAC) is involved in an early step of nucleotide excision repair, the main process that removes UV damage and many chemical lesions from DNA. To explore the properties and function of XPAC, recombinant protein encoded by the human XPAC cDNA was expressed with an N terminal polyhistidine tag in Escherichia coli and purified to homogeneity. The soluble fusion protein could correct the repair defect in vitro of XP-A cell extracts. XPAC protein bound to DNA with a preference for UV-irradiated over nonirradiated DNA, as determined by a gel electrophoresis mobility shift assay with a 258 base pair DNA fragment (the association constant was approximately 3 x 10(6) M-1 for the fragment irradiated with 6 kJ/m2 UV light). Removal of cyclobutane pyrimidine dimers from UV-irradiated DNA by enzymatic photoreactivation did not significantly reduce binding of XPAC to the irradiated fragment, indicating that binding was mostly due to (6-4) photoproducts, with a preference for a (6-4) photoproduct over an undamaged base pair up to 300-fold. Undamaged single-stranded DNA competed about 4-fold more effectively than undamaged double-stranded DNA for binding of XPAC to a UV-irradiated fragment. In addition, XPAC bound to DNA treated with the chemotherapeutic agent cis diamminedichloroplatinum(II). The results suggest that XPAC functions as a key component in recognition of DNA damage during repair. PMID- 8218289 TI - Substrate specificity of the Escherichia coli endonuclease III: excision of thymine- and cytosine-derived lesions in DNA produced by radiation-generated free radicals. AB - The excision of modified bases from DNA by Escherichia coli endonuclease III was investigated. Modified bases were produced in DNA by exposure of dilute buffered solutions of DNA to ionizing radiation under oxic or anoxic conditions. The technique of gas chromatography/mass spectrometry (GC/MS) was used to identify and quantify 16 pyrimidine- and purine-derived DNA lesions. DNA substrates were incubated either with the native enzyme or with the heat-inactivated enzyme. Subsequently, DNA was precipitated. Pellets were analyzed by GC/MS after hydrolysis and derivatization. Supernatant fractions were analyzed after derivatization without hydrolysis. The results provided unequivocal evidence for the excision by E. coli endonuclease III of a number of thymine- and cytosine derived lesions from DNA. These were 5,6-dihydrothymine, 5-hydroxy-5 methylhydantoin, thymine glycol, 5-hydroxy-6-hydrothymine, 5,6-dihydrouracil, alloxan, uracil glycol, and 5-hydroxy-6-hydrouracil. None of the purine-derived lesions was excised by endonuclease III. The present work extends the substrate specificity of E. coli endonuclease III to another thymine-derived and four cytosine-derived lesions. It is the first investigation of the substrate specificity of this repair enzyme in the context of a large number of pyrimidine- and purine-derived lesions in DNA. PMID- 8218290 TI - Transthyretin mutation Leu-55-Pro significantly alters tetramer stability and increases amyloidogenicity. AB - A recently reported variant of human transthyretin (TTR), Leu-55-Pro, implicated as the causative agent in early-onset familial amyloid polyneuropathy was expressed and characterized, and its denaturation pathway and amyloidogenicity were compared to those of wild-type transthyretin. The overlap-extension polymerase chain reaction (PCR) methodology was used to introduce the Leu-55-Pro mutation into the transthyretin DNA sequence and to construct a new expression system. The Leu-55-Pro variant of transthyretin was expressed with a leader sequence to ensure secretion into the periplasmic space of Escherichia coli. Transthyretin's resistance to sodium dodecyl sulfate- (SDS-) induced denaturation was utilized to measure the quaternary stability as a function of pH employing SDS-polyacrylamide gel electrophoresis (PAGE) in the presence and absence of an amyloid fibril inhibitor, Z 3-14. These studies reveal that the Leu-55-Pro TTR tetramer is significantly less stable than wild-type TTR. This is relevant because we have previously shown that the partial denaturation of transthyretin is sufficient to effect amyloid fibril formation from a denaturation intermediate which may be a structured monomer. The ability of Leu-55-Pro TTR to denature to the amyloidogenic intermediate at pHs where the wild-type protein is stable may explain the variant's propensity to form amyloid fibrils in vitro and in vivo where the wild-type protein remains stable and nonamyloidogenic. Congo red binding, polarized light microscopy, and electron microscopy confirm the characteristic structure of amyloid fibrils produced from Leu-55-Pro TTR in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218291 TI - Isoabzymes: structurally and mechanistically similar catalytic antibodies from the same immunization. AB - Mechanistic and structural comparisons of five catalytic monoclonal antibodies generated from the same hybridoma fusion indicated that all five hydrolyze phenyl acetate by subtle variations of the same mechanism. All of the antibodies showed a pre-steady-state multi-turnover burst in which kcat and Km declined but kcat/Km did not change. The burst of one of the antibodies, 20G9, has previously been found to result from inhibition by the product, phenol. Although all of the antibodies showed the burst, their individual values for kcat, Km, and hapten Ki differed substantially. Three of the antibodies that were investigated for the effect of pH on kcat showed an acid limb pK of 9.5-9.6. Substrate inhibition was seen in four of the five antibodies. Variable region nucleotide sequencing of the heavy and light chains confirmed that all five antibodies were structurally similar and also revealed several potentially critical tyrosines. Despite their structural similarities, analysis of their sequences suggested that the antibodies are products of distinct, independent rearrangements of immunoglobulin gene segments that took place in different progenitor B cells. A plot of Ki for hapten inhibition vs Km/kcat for substrate hydrolysis for the mechanistically related antibodies ("isoabzymes") gave a linear relationship suggesting a catalytic role for transition-state complementarity. Taken together with previous work [Martin et al. (1991) Biochemistry 30, 9757-9761], the data conform to a mechanism in which the antibodies exploit both transition-state complementarity and an acyl-tyrosyl intermediate during phenyl acetate hydrolysis. PMID- 8218292 TI - Parallel mechanisms of high molecular weight kininogen action as a cofactor in kallikrein inactivation and prekallikrein activation reactions. AB - The mechanism by which high molecular weight kininogen (H-kininogen) potentiates the heparin-accelerated inhibition of plasma kallikrein by antithrombin [Olson, S. T., Sheffer, R., & Francis, A. M. (1993) Biochemistry (preceding paper in this issue)] was investigated at I = 0.15, pH 7.4, 25 degrees C. Single-chain, two chain, and light-chain, but not heavy-chain, forms of H-kininogen were similarly effective in potentiating the heparin-accelerated antithrombin-kallikrein reaction, indicating that the light-chain region of the protein was responsible for promoting kallikrein inactivation and that cleavage of H-kininogen did not significantly affect this promoting activity. H-kininogen potentiation increased in a saturable manner with increasing kininogen concentration, reflecting a KD (23 +/- 8 nM) similar to that previously measured for H-kininogen binding to kallikrein by equilibrium methods. Both H-kininogen-stimulated and unstimulated heparin rate enhancements initially increased with increasing heparin concentration in a manner corresponding to the saturation of antithrombin with heparin (KD = 10-30 nM). However, at higher heparin concentrations, the stimulated but not the unstimulated heparin rate enhancement decreased in parallel with the saturation of a protein-heparin interaction with a KD (0.4 +/- 0.2 microM) comparable to that directly measured for the H-kininogen-heparin interaction (2.0 +/- 0.2 microM). These results implied that H-kininogen stimulation required the formation of a quaternary complex in which antithrombin and H-kininogen-kallikrein complex were bound to the same heparin chain. In keeping with this interpretation, a synthetic heparin pentasaccharide representing the antithrombin binding sequence accelerated the antithrombin kallikrein reaction to an extent similar to that of full-length heparin chains containing this sequence, but the pentasaccharide acceleration was not stimulated by H-kininogen. The importance of H-kininogen-kallikrein complex binding to heparin for kininogen stimulation was further indicated from the marked salt dependence of the second-order rate constant for the association of H-kininogen kallikrein complex but not free kallikrein with antithrombin-heparin complex, under conditions where saturation of the two binary complexes was maintained. Kinetic analyses of antithrombin-kallikrein reactions as a function of the inhibitor concentration indicated that the KD for an initial antithrombin kallikrein encounter complex was decreased 20-fold by heparin binding to antithrombin and an additional 200-fold by H-kininogen also binding to kallikrein. By contrast, rate constants for the conversion of the encounter complex to a stable complex were comparable for all reactions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8218293 TI - The pro region required for folding of carboxypeptidase Y is a partially folded domain with little regular structural core. AB - The pro region of carboxypeptidase Y (CPY) from yeast is necessary for the correct folding of the enzyme [Winther, J. R., & Sorensen P. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 9330-9334]. Using fluorescence, circular dichroism, and heteronuclear NMR analyses, it is demonstrated that the isolated pro region is a partially folded protein domain under the conditions where it is functional. It is characterized by a relatively high content of secondary structural elements but a very low content of defined tertiary structure. Although these characteristics are reminiscent of the compact denatured states that have been identified as intermediates in protein folding ("molten globules"), the pro region exhibits only very weak binding of the hydrophobic probe 1-anilino-8 naphthalenesulfonate, and it is resistant toward complete thermal unfolding. Altogether the data indicate an extremely flexible structure that has little regular structural core. It is proposed that the feature of a partially folded domain per se is important for the function of the pro region of CPY as a "co translational chaperone". PMID- 8218294 TI - Helical structure and folding of subunit c of F1F0 ATP synthase: 1H NMR resonance assignments and NOE analysis. AB - Subunit c of the H(+)-transporting F1F0 ATP synthase (EC 3.6.1.34) is thought to fold across the membrane as a hairpin of two alpha-helices and function as a key component of the H(+)-translocase of F0. We report here the initial results of a structural study of purified subunit c in a chloroform-methanol-water (4:4:1) solvent mixture using standard two-dimensional NMR techniques. The spin systems of 78 of the 79 amino acid side chains have been assigned to residue type, and 44 of these have been assigned to specific residues in the sequence. Stretches of alpha-helical secondary structure were observed for Asp7-ILe26 in the first proposed transmembrane helix, and for Arg50-Ile55 and Ala67-Val78 in the second proposed transmembrane helix. Nuclear Overhauser effects (NOEs) were observed between residues at both ends of the predicted transmembrane helices. The intensities of the NOEs between helix-1 and helix-2 were not diminished by mixing of 2H-subunit c with 1H-subunit c, and therefore the NOEs must be due to intramolecular, rather than intermolecular, interactions. Hence the purified protein must fold as a hairpin in this solvent system, just as it is thought to fold in the lipid bilayer of the membrane. In native F0, dicyclohexylcarbodiimide reacts specifically with Asp61 in the second transmembrane helix of subunit c, and the rate of this reaction is reduced by substitution of Ile28 by Thr on the first transmembrane helix. The I28T substitution is shown here to alter the chemical shifts of protons at and around Asp61. This observation provides a further indication that subunit c may fold in chloroform-methanol-water solvent much like it does in the membrane. PMID- 8218295 TI - Sodium- and chloride-dependent, cocaine-sensitive, high-affinity binding of nisoxetine to the human placental norepinephrine transporter. AB - Maternal-facing brush border membranes prepared from normal term human placentas possess the norepinephrine transporter. We investigated the interaction of nisoxetine with the human norepinephrine transporter by examining the binding of this ligand to the placental brush border membranes. Scatchard analysis revealed that nisoxetine bound with high affinity to a single class of binding sites in the membranes (dissociation constant = 13.8 +/- 0.4 nM). This value obtained from equilibrium experiments matched the value (11.2 nM) which was calculated using the association and dissociation rate constants. The maximal binding capacity (Bmax) was 5.1 +/- 0.1 pmol/mg of protein. The binding exhibited an absolute requirement for Na+ as well as Cl-. Presence of these ions enhanced the binding affinity without affecting Bmax. Kinetic analyses revealed that the coupling ratio of Na+/nisoxetine was 2, whereas the coupling ratio of Cl-/nisoxetine was 1. The binding was most potently inhibited by the ligands of the norepinephrine transporter (desipramine and nomifensine). The ligands of the serotonin transporter (imipramine, paroxetine, and fluoxetine) showed intermediate inhibitory potencies, whereas the ligands of the dopamine transporter (bupropion and GBR 12909) were the least potent. Among the monoamines, dopamine was the most potent inhibitor, followed by norepinephrine and serotonin. Though both cocaine and its analog RTI-55 were powerful inhibitors of the binding, RTI-55 was approximately 150 times more effective than cocaine. The inhibition of binding by norepinephrine, cocaine, and RTI-55 was competitive. Uptake of norepinephrine measured in membrane vesicles was found to be inhibited by treatment of the vesicles with phenylarsine oxide, a reagent specific for vicinal dithiol groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218296 TI - Structural characterization of membrane insertion of M13 procoat, M13 coat, and Pf3 coat proteins. AB - A new, simple, and efficient purification method has been developed for the extremely hydrophobic M13 procoat, M13 coat, and Pf3 coat proteins. Homogeneous preparations were obtained in 2-propanol/0.1% TFA, where M13 coat protein is found to be dissolved in a monomeric form, and the two other proteins as dimers or trimers. The conformations of these particular proteins in different environments have been determined by circular dichroism and infrared spectroscopy. In organic solvents, the proteins adopt a conformation with an average helix content of 90%. In lipid bilayers composed of phosphatidylcholine and phosphatidylglycerol lipids, the average helix content is 50% for M13 procoat protein, 60% for M13 coat protein, and 75% for Pf3 coat protein. The orientational order parameter S alpha of the protein helices in planar lipid bilayers have been determined by polarized infrared measurements in the amide I spectral range. The helices of the three proteins are oriented preferentially parallel to the membrane normal, with S alpha = 0.63 for M13 procoat protein, S alpha = 0.58 for Pf3 coat protein, and a distinctly higher value of S alpha = 0.81 for M13 coat protein. PMID- 8218297 TI - The antiviral peptide carbobenzoxy-D-phenylalanyl-L-phenylalanylglycine changes the average conformation of phospholipids in membranes. AB - The influence of the antiviral peptide, carbobenzoxy-D-phenylalanyl-L phenylalanylglycine (ZfFG), on the average conformation of phosphatidylcholine in hydrated bilayers was investigated with multinuclear solid state magnetic resonance (NMR). Phosphatidylcholine was specifically deuterated (separately) in the choline N-methyls, the alpha and beta positions of the choline, the C2 carbon of the acyl chains, and at all the carbons of the acyl chains of the phosphatidylcholine. Phosphatidylcholine was also synthesized with the carbonyl carbons of the ester bonds between the glycerol and the hydrocarbon chains enriched in 13C. 2H NMR of the phosphatidylcholine perdeuterated in the acyl chains showed a loss of intensity from the deuteriums with the largest quadrupole splitting in the presence of ZfFG, while the remainder of the powder pattern was largely unaffected. The phosphatidylcholine specifically deuterated at the C2 carbon (representative of the C-D bonds giving rise to the largest quadrupole splittings) showed the same loss of intensity suggesting changes in the phospholipid conformation and conformational dynamics near the glycerol. Analysis of the powder patterns in the 13C NMR spectrum of phosphatidylcholine labeled with 13C in the carbonyl carbons revealed a significant change in the average orientation of the sn-1 carbonyl due to the presence of the ZfFG and no change in the sn-2 carbonyl orientation. Changes in the headgroup conformation, as detected by 2H NMR of the deuteriums in the alpha and beta methylenes of the choline headgroup and 31P NMR of the phosphate segment, reflected the electrostatic nature of the interaction of the carboxyl of ZfFG with phosphatidylcholine bilayers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218298 TI - Transient activation of calcium-dependent phospholipase A2 by insulin secretagogues in isolated pancreatic islets. AB - Arachidonic acid is believed to be an important and necessary mediator of insulin secretion by beta-cells of islets of Langerhans, and it may regulate intracellular Ca2+ homeostasis. Insulin secretagogues, such as glucose and the muscarinic agonist carbachol, stimulate arachidonic acid accumulation, although the mechanisms involved are controversial: carbachol is believed to stimulate phospholipase A2, while glucose-induced arachidonic acid release is the result of diacylglycerol hydrolysis [Konrad, R. J., et al. (1992) Biochem. J. 287, 283 290]. In insulin-secreting clonal beta-cells RINm5F, HIT-T15, and beta-TC3, Ca(2+)-independent phospholipase A2 was mainly cytosolic, while in islets it was equally distributed between a crude membrane fraction and the cytosol. A membrane associated Ca(2+)-dependent phospholipase A2 was found to be stimulated by millimolar Ca2+ concentrations, while a cytosolic Ca(2+)-dependent activity was activated by micromolar Ca2+ levels. In order to determine whether phospholipase A2 was activated in insulin secretion, we assessed whether pretreatment of intact islets with secretagogues affected phospholipase A2 activity, which was subsequently measured in membrane or cytosolic fractions. The combination of glucose and carbachol transiently activated Ca(2+)-dependent (but not Ca(2+) independent) phospholipase A2 activity at 10 min, which corresponded to the peak of arachidonic acid release. No effect was seen with either agonist alone. Our results indicate that activation of Ca(2+)-dependent phospholipase A2 may be due to agonist-induced increases in intracellular Ca2+. We suggest that activation of islet Ca(2+)-dependent phospholipase A2 may be important in a distal process of insulin secretion, such as secretory granule exocytosis. PMID- 8218299 TI - Mechanism of intermembrane phosphatidylcholine transfer: effects of pH and membrane configuration. AB - The mechanism of phospholipid transfer between membranes has been studied as a function of the configuration and concentration of donor and recipient membranes. The study was motivated by the observation that dimyristoylphosphatidylcholine transfers from sonicated vesicles to erythrocytes at a 4-fold faster rate at pH 5.5 than at pH 7.4. It is unexpected that the solubility of phosphatidylcholine should be affected by pH changes in this range; indeed, the more hydrophilic homolog dilauroylphosphatidylcholine transfers at closely similar rates at pH 5.5 and 7.4. The behavior of the more hydrophobic lipid is not consistent with transfer solely as a monomer passing through the aqueous phase. The effects of membrane proximity on phospholipid transfer were examined in dilution experiments employing intact erythrocytes, resealed ghosts, erythrocyte membrane buds, and sonicated vesicles as both donor and recipient membranes. For both hydrophobic and less hydrophobic lipids, the kinetics of intermembrane transfer were affected significantly by dilution at constant donor:recipient ratios. The results were fit to a kinetic model containing contributions from both through-solution monomer transfer and transient collisional transfer. The model predicts that the mechanism of intermembrane transfer varies with experimental conditions such as membrane concentration, donor and acceptor membrane area, and surface curvature. Through-solution monomer transfer predominates for less hydrophobic lipids at all values of pH and membrane concentration, and for more hydrophobic lipids at very high membrane dilutions. Transient collisional transfer contributes significantly to the rate for relatively hydrophobic lipids in concentrated donor-acceptor systems, an effect that is particularly evident at pH values below 6. The size and surface configuration of donor and recipient membranes also alter the relative contributions of through-solution and collisional transfer. PMID- 8218300 TI - Escherichia coli aromatic amino acid aminotransferase: characterization and comparison with aspartate aminotransferase. AB - Aromatic amino acid aminotransferase (ArAT) from Escherichia coli was overexpressed in E. coli cells, purified, and characterized. The enzyme was similar to aspartate aminotransferase (AspAT) of E. coli in many aspects, such as gross protein structure and spectroscopic properties. The reactions of pyridoxal 5'-phosphate-form ArAT with amino acids and pyridoxamine 5'-phosphate-form ArAT with oxo acids were investigated using stopped-flow spectrophotometric techniques. The kinetic parameters for these "half" reactions could excellently explain the ArAT-catalyzed overall transamination reactions at pH 8.0. Reactions of ArAT with aspartate and tryptophan which had been deuterated at position 2 showed isotope effects of 2.5 and 6.0 in the kcat values of the half-reactions, showing that the proton-transfer step is at least partially rate-limiting for these reactions. ArAT and AspAT showed overlapping substrate specificity. Both ArAT and AspAT were active toward dicarboxylic substrates. ArAT showed, however, 10(3)-fold higher activity toward aromatic substrates than AspAT. This high activity toward aromatic substrates was in part ascribed to the active site hydrophobicity of ArAT, which was suggested to be about 1.4 times as large as that of AspAT. In addition to dicarboxylic substrate analogs, aromatic substrate analogs such as carboxylic acids, 2-methyl amino acids, and 3-hydroxy amino acids caused characteristic changes in the absorption spectra of ArAT, while these aromatic analogs did not significantly change the spectra of AspAT. In particular, the erythro-3-hydroxy analogs of phenylalanine and aspartate caused a prominent absorption of ArAT at around 500 nm, which is generally ascribed to the accumulation of quinonoid intermediates. The threo forms of these 3-hydroxy analogs acted as substrates for ArAT. The erythro and threo forms of 3 hydroxyaspartate reacted with AspAT similarly as they reacted with ArAT; however, both forms of 3-phenylserine were poor substrates for AspAT, although phenylalanine was a fairly good substrate for AspAT. The observations on the two erythro-3-hydroxy amino acids show the similar orientation of these analogs in the active site of ArAT, probably through a hydrogen-bonding network involving the hydroxy groups of the analogs and Tyr70, and suggest that the aromatic binding pocket is near or even overlaps the side-chain-carboxylate-binding site for dicarboxylic substrates. PMID- 8218301 TI - Sources of acetyl-CoA entering the tricarboxylic acid cycle as determined by analysis of succinate 13C isotopomers. AB - A new 13C NMR technique for measuring substrate utilization by the citric acid cycle based on an analysis of succinate 13C isotopomers is presented. The relative contribution of up to three different labeling patterns in acetyl-CoA entering the citric acid cycle may be determined under non-steady-state conditions. We present experimental data from perfused rat hearts subjected to a brief period of ischemia, where both succinate and glutamate resonances were observed in the 13C spectrum. The contributions of labeled exogenous acetate and lactate and unlabeled sources to the acetyl-CoA pool were compared using this succinate analysis and a previously published glutamate analysis [Malloy et al. (1990) Biochemistry 29, 6756-6761], and the two methods give identical results. This indicates that the succinate and glutamate isotopomers originated from a common alpha-ketoglutarate pool, verifying that glutamate is in isotopomeric equilibrium with alpha-ketoglutarate under these conditions. PMID- 8218302 TI - Specificity of 4-chlorobenzoyl coenzyme A dehalogenase catalyzed dehalogenation of halogenated aromatics. AB - Steady-state and transient kinetic techniques were used to evaluate the efficiency of 4-chlorobenzoyl coenzyme A (4-CBA-CoA) turnover catalyzed by 4-CBA CoA dehalogenase from Pseudomonas sp. CBS-3. The kcat for a single turnover on the enzyme was found to be 2 s-1, while that for multiple turnovers was found to be 0.6 s-1. Catalysis rather than product release was judged to be rate limiting. Comparison of the rates of turnover of 4-bromobenzoyl-CoA (1.4 s-1), 4 iodobenzoyl-CoA (1.1 s-1), and 4-fluorobenzoyl-CoA (8 x 10(-6) s-1) indicated that cleavage of the carbon-halogen bond occurs in the rate-limiting transition state of the reaction. Structure-activity measurements made with 4-CBA-CoA analogs bearing electron-donating or -withdrawing substituents at C(2) or C(3) suggested the importance of steric/solvation effects on the enzymatic reaction and failed to provide insight into the nature of the reaction intermediate. The inhibition constants measured for benzoyl-CoA (72 microM), CoA (140 microM), and 4-chlorobenzoate (21 mM) compared to the Km measured for 4-CBA-CoA (4 microM) suggest the dominant role played by the CoA moiety in substrate anchoring. PMID- 8218303 TI - Bacterial protein disulfide isomerase: efficient catalysis of oxidative protein folding at acidic pH. AB - Periplasmic protein disulfide isomerase (DsbA) is essential for disulfide formation in Escherichia coli. The tryptophan fluorescence of DsbA measures the redox state of the enzyme during catalysis of the oxidative folding of hirudin, a thrombin inhibitor containing three disulfide bonds and lacking tryptophan. With stoichiometric amounts of DsbA, reduced hirudin is rapidly oxidized in a process initially leading to random disulfides. Disulfide reshuffling involving reduced DsbA yields completely native inhibitor within 1 h, even at pH 4. Catalytic amounts of DsbA become essential for hirudin folding in the presence of redox buffers at acidic pH. The second-order rate constants of disulfide exchange reactions involving DsbA are several orders of magnitude above the known values for alkyl dithiols and disulfide oxidoreductases. DsbA preferably reacts with reduced, unfolded polypeptides. The reduction of DsbA by hirudin is faster by 1 order of magnitude than its reduction by the strong reductant dithiothreitol. Together, unusually fast disulfide interchange reactions and a preference for folding polypeptides appear to be responsible for the catalytic efficiency of DsbA and for disulfide formation in vivo at acidic pH. PMID- 8218304 TI - Regulation of a candidate aminophospholipid-transporting ATPase by lipid. AB - The effect of lipid environment on the activation of a vanadate-sensitive Mg(2+) ATPase purified from human erythrocytes was studied in detergent-lipid-protein mixed micelles. ATPase activity was stimulated maximally by phosphatidylserine. Other anionic diacylglycerophospholipids (phosphatidic acid, cardiolipin, phosphatidylglycerol, and phosphatidylinositol) supported 25-100% of the phosphatidylserine-stimulated activity. Another aminophospholipid, egg PE, supported 38% of the phosphatidylserine-stimulated activity. The phosphoinositides (phosphatidylinositol, phosphatidylinositol 4-phosphate, phosphatidylinositol 4,5-bisphosphate) also stimulated the ATPase; however, activity decreased with increasing lipid phosphorylation. Monoacyl negatively charged lipids (lysophosphatidylserine, fatty acids) and zwitterionic lipids (phosphatidylcholine and sphingomyelin) did not activate the enzyme. ATPase activation was dependent on phospholipid fatty acyl chain composition: ATPase activity increased with increasing PS acyl chain length, and the optimal fatty acid composition was one saturated and one unsaturated fatty acid. However, the long, unsaturated acyl chain requirement could be satisfied by nonactivating lipids. The characteristics of this ATPase are similar to those of the Mg(2+)-ATP dependent aminophospholipid flippase, suggesting that it may be associated with the transporter. PMID- 8218305 TI - Structure-activity correlations of melanotropin peptides in model lipids by tryptophan fluorescence studies. AB - Steady-state and time-resolved fluorescence spectroscopy were employed in the study of the structure and interactions of alpha-MSH (alpha-melanocyte stimulating hormone) and its analogs, [Nle4,D-Phe7]-alpha-MSH (MSH-I) and Ac [Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH(4-10)-NH2 (MSH-II). In aqueous buffer, the fluorescence parameters of the single tryptophan of alpha-MSH and MSH-I were similar and did not allow any distinction between these molecules. On the other hand, the tryptophan fluorescence of MSH-II was notably different, reflecting its cyclic lactam turn structure. In the presence of acidic lipid vesicles, the fluorescence properties of the peptides were different, indicating structural changes on incorporation of the peptide into the liquid-crystalline phase of the lipid. No evidence of interaction was observed in the presence of the neutral lipid dimyristoylphosphatidylcholine (DMPC). The association constants for lipid peptide interactions were compared for binding isotherms which either neglected or accounted for electrostatic effects through Gouy-Chapman potential functions. The relative order of association constants in either treatment was MSH-II > MSH I > alpha-MSH. These results parallel the reported biological activities that show increased potencies and prolongation of response for the analogs, MSH-II and MSH-I, as compared to the native hormone, alpha-MSH. Time-resolved fluorescence results showed that the fluorescence decay of melanotropins is best described by triple-exponential kinetics. In the lipid-peptide complex, there was a change in the relative concentrations of the components, with the intermediate-lifetime component predominating compared to those in solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218306 TI - Soft-palate myogenesis: a developmental field paradigm. AB - Surgical correction of clefts of the soft palate leads to varying degrees of normal function although the repair itself is successful. Explanations for this include structural abnormalities of the muscles. Previous studies have focused primarily on gross anatomical features of late fetal and postnatal cleft palate musculature; however, infrequent reference has been made to early prenatal morphologic patterns of soft-palate development, beginning with the embryo. Thus we evaluated the chronology of prenatal myogenesis of the soft palate from its early mesenchymal phase through the appearance of definitive palatal muscles and associated structures in a sample of 22 human fetuses that represented postfertilization weeks 6.5 to 20.5 (18- to 192-mm crown-rump length). Specimens were histologically prepared for descriptive and morphometric light microscopy. Data were collected on the earliest appearance times of identifiable soft palate and associated structures within the mesenchymal field and on their individual stages of myogenesis (e.g., for muscles, from mesenchyme to myoblasts to fascicles). Analyses showed that (1) palatal muscles and related bony structures emerge sequentially as densely staining mesenchymal subfields within the larger mesenchymal soft-palate field during the 6- to 9-week period, with the tensor veli palatini muscle appearing earliest, and the musculus uvulae latest; (2) further morphogenesis of the soft palate and associated structures follows a definite timeline; and (3) by 16 to 17 weeks the postnatal palatal morphology is in place. PMID- 8218307 TI - Genetic survey of a group of children with clefting: implications for genetic counseling. AB - A cleft lip, cleft palate, or both are associated with a high frequency of other anomalies. This study gives an inventory of associated anomalies in a consecutive group of children (n = 36) with clefts, referred to a local multidisciplinary cleft team in the Netherlands. In 47.2% of cleft patients associated anomalies were found, allowing diagnosis of provisionally unique syndromes or known entities. In 17 patients family history was positive for clefting; in five patients (13.9%) this influenced the occurrence risks for siblings. Both findings had an effect on genetic counseling of the parents of these children. Additional evidence is provided that all children with clefting should be carefully evaluated by a trained clinician for additional anomalies, including dysmorphic features. PMID- 8218308 TI - Intraoperative suction test as a predictor of velopharyngeal competence. AB - A simple, inexpensive intraoperative test to estimate the probability of adequate speech development following cleft palatal or pharyngeal flap surgery is described. Its results were reviewed in 151 patients over a 10-year period. The positive predictive value of the test is 92% for not requiring further surgery and 83% for development of adequate speech. The results and their meaning are discussed. PMID- 8218309 TI - Soft-tissue profile changes during widening and protraction of the maxilla in patients with cleft lip and palate compared with normal growth and development. AB - During the last 15 years, cleft lip and palate (CLP) patients with maxillary deficiency in the care of the Bergen CLP team have undergone an interceptive orthopedic treatment phase during the deciduous and mixed dentition period. The present study includes 68 patients who received maxillary transverse expansion by use of a modified quad-helix appliance and 98 cases given maxillary protraction by a facial mask. All cases were treated until an acceptable normal occlusion was attained. Lateral cephalograms were taken immediately before and after the active treatment periods. Sagittal changes of the soft-tissue profile during transverse expansion and protraction were analyzed separately for unilateral complete cleft lip and palate (UCLP) patients and bilateral complete cleft lip and palate (BCLP) patients. The soft-tissue profiles of the groups were compared to growth changes of noncleft age-matched children (NORM group). During the short period of maxillary transverse expansion (mean period, 3.5 months) no significant change of the soft-tissue profile was found, except in the protrusion of the lower lip in the BCLP group. During the period of maxillary protraction (mean periods, 12 months in the UCLP group and 15 months in the BCLP group) the soft-tissue profile improved significantly by reducing the characteristic tendency towards a concave profile in CLP patients with maxillary deficiency. Significant increases of the sagittal maxillomandibular lip relation (angle SS-N-SM: mean increase, 2.5 degrees) and the Holdaway-angle (H-angle: mean increase, 3.0 degrees) were found to be similar in the UCLP and BCLP groups. However, the use of different reference lines for evaluation of treatment effects upon the soft-tissue profile resulted in conflicting findings suggesting that anteriorly situated reference lines are more suitable for the evaluation of CLP patients. Thus, the esthetic line (E.line) indicated a favorable position of the lips after treatment; the subspinale-pogonion line (ss.pg) revealed an improved soft-tissue profile; the soft-tissue-facial line (N.PG) showed a retruded nose and upper lip; whereas basal references such as the nasionsella line (NSL) and the occlusal-line perpendicular (OLP) mainly showed major differences between the CLP groups and the NORM groups. PMID- 8218310 TI - Isolated cleft palate in Danish multiple births, 1970-1990. AB - The etiology of most cases of isolated cleft palate (CP) is unknown. The relative importance of genes and environment can be studied using the classical twin method but only few and potentially highly selected CP twin data are available. The present CP twin study was based on four Danish nationwide ascertainment sources of CP multiple births in the period 1970-1990. The ascertainment sources covered the time period from 15 completed weeks of pregnancy to adolescence for the older cohorts. A total of 18 CP cases in multiple births were identified; two monozygotic twin pairs of which one was concordant and eight were dizygotic, discordant twin pairs. Three cases were from two triplet sets, and four discordant twin pairs were of unknown zygosity. The twin concordance rates suggest that genetic factors play a major role in the etiology of CP, but environmental and/or stochastic factors are probably acting as well. PMID- 8218311 TI - Social skills of preschoolers with and without craniofacial anomalies. AB - The study compared the social skills of preschoolers with and without craniofacial anomalies (CFA). Fifty-two children completed self-perception and facial expression tasks and a social skills interview. Parents and teachers also rated the children's social skills. Children with CFA gave less friendly responses to hypothetical social situations and were rated as less attractive by graduate students. Girls with CFA reported above average self-perceptions. Patients and teachers rated the children with CFA as having a level of social skills equal to the children without CFA. Different factors were predictive of level of social skills for CFA and control children. PMID- 8218312 TI - Psychological functioning of children with craniofacial anomalies and their mothers: follow-up from late infancy to school entry. AB - Twenty-three mothers and their 5- to 7-year-old children with craniofacial anomalies (CFA) who were assessed during the child's infancy were followed. Three types of CFA were included: cleft lip and palate (CLP), isolated cleft palate (CP), and sagittal synostosis. Measures of child status focused on behavior problem frequency and self-concept. Mothers completed self-report measures of emotional well-being, marital satisfaction, and social support. Results indicated that (1) a sizable minority (18%) of the children with CFA had clinically significant behavior-problem scores shown in concordant reports by parent and teacher of behavior problems; (2) individual differences in child functioning within the CFA group were predicted by observational measures of earlier mother infant interaction during play and teaching situations; (3) mothers of children with CLP reported less favorable social support than mothers of children with CP or sagittal synostosis. PMID- 8218313 TI - Effect of parental factors on social skills of preschool children with craniofacial anomalies. AB - This study investigated the parenting stress and style and the social networks of parents with preschool children with and without craniofacial anomalies (CFA), and the effect of these factors on the child's level of social skill. Fifty-two families participated in the study. No differences were found between the CFA and control groups on level of parenting stress, parenting style, or social network characteristics. However, parents with children with visible defects found their social support networks more helpful, and advocated a more nurturing parenting style. For the CFA group, parenting stress predicted child level of social skill. These results underscore the importance of investigating the interaction between parent and child factors. PMID- 8218314 TI - Unilateral absence of the soft palate: case report of reconstruction with a mucoperiosteal island flap. AB - Congenital absence of half of the soft palate is a rare deformity. There is little in the literature about its definition and management. This article presents a case with velopharyngeal insufficiency caused by unilateral absence of the soft palate. The patient was treated with a modification of the mucoperiosteal island flap, first designed by Millard, to provide nasal lining during pushback lengthening of a short cleft palate. The speech quality of the patient improved noticeably after the operation. Although island flap has limited use in primary cleft palate surgery, it may be effective in reconstruction of soft palate defects, when standard pushback procedures are not adequate for solving the problem. PMID- 8218315 TI - The velopharyngeally inadequate child: phonologic change with intervention. AB - Diagnostic therapy is often recommended for children before physical management of the velopharyngeal structures. There is, however, limited information about the effectiveness of such intervention programs. This study describes the changes that occurred in a 3-year-old child's production of speech during a period of diagnostic therapy, and the changes that occurred following the fitting of a prosthesis. The mother served as the primary intervener, guided by a speech language pathologist. The mother was able to change the child's speech so that more of her productions were at a correct place of articulation. After structural management, nasal and glottalized productions disappeared from the child's speech, but glottal stops did not. PMID- 8218316 TI - Social improvement after the Wilke procedure for excessive drooling. AB - The child with an excessive drooling problem often faces similar social deprivation to those with severe craniofacial malformations. Many of these children have other "strikes against them" (such as cerebral palsy) that, when coupled with drooling, isolate them from social interaction. Many methods have been employed to control drooling but surgery has been most consistently successful. The most popular of these has been the Wilke procedure or a modification of it. Several series have been reported, but a detailed correlation of mechanical success with the effects on social activity has not been reported. We reviewed a series of 23 cases of Wilke-type surgery. Analysis of the results showed a convincing improvement in social activity after successful surgery. The Wilke procedure enjoys a relatively high rate of success in preventing excessive drooling, which seems to offer a dramatic improvement in social contact enjoyment. PMID- 8218317 TI - My friend the cranial base: why is it so normal? PMID- 8218318 TI - Neurocranial morphology in mandibulofacial dysostosis (Treacher Collins syndrome). Figueroa et al., July 1993, Vol. 30, No. 4, 369-375. PMID- 8218319 TI - Nasal resistance and breathing mode. PMID- 8218320 TI - Kinetical parameters of monovalent cation uptake in yeast calculated on accounting for the mutual interaction of cation uptake and membrane potential. AB - Kinetical parameters of monovalent cation uptake in yeast are calculated according to a model for mutual interaction of membrane potential and cation uptake. Apparent Km values for monovalent cation uptake obtained from uptake studies are 3-5-times lower than the Km values expected when the membrane potential remains constant at increasing cation concentrations instead of being reduced. The model accounts for various phenomena as (i) the increase in apparent Km of Rb+ uptake accompanying the decrease in maximum rate of uptake found on increasing the cellular K+ content, (ii) the decrease in maximum uptake rate and increase in Km in case of simultaneous transport of phosphate and Rb+, (iii) the change in the maximum uptake rate without a change in Km under conditions that the proton pump is effected and (iv) the absence of an increase in K+ efflux at high depolarizing external cation concentrations. PMID- 8218321 TI - Electrical properties of cell pellets and cell electrofusion in a centrifuge. AB - A new approach is proposed for studying cell deformability by centrifugal force, electrical properties of cell membranes in a high electric field, and for performing efficient cell electrofusion. Suspensions of cells (L929 and four other cell types examined) are centrifuged in special chambers, thus forming compact cell pellets in the gap between the electrodes. The setup allows measurement of the pellet resistance and also the high-voltage pulse application during centrifugation. The pellet resistance increases sharply with the centripetal acceleration, which correlates with reduction of the cell pellet porosity due to cell compression and deformation. Experiments with cells pretreated with cytochalasin B or colcemid showed that cell deformability depends significantly on the state of cytoskeleton. When the voltage applied to the cell pellet exceeds a 'critical' value, electrical breakdown (poration) of cell membranes occurs. This is seen as a deflection in the I(V) curve for the cell pellet. The electropores formed during the breakdown reseal in several stages: the fastest takes 0.5-1 ms while the whole process completes in minutes. A novel effect of colloid-osmotic compression of cell pellets after electric cell permeabilization is described. Supercritical pulse application to the cell pellet during intensive centrifugation leads to massive cell fusion. The fusion index grows with the increase of centripetal acceleration, and drops drastically when the pulse is applied after the centrifuge is stopped. The colloid-osmotic pellet compression enhances the fusion efficiency. No fusion occurs when cells are brought in contact after the pulse treatment. The data suggest that tight intermembrane contact formed prior to pulse application is a prerequisite condition for efficient cell electrofusion. The capacities of the technique proposed and the mechanism of membrane electrofusion are discussed. PMID- 8218322 TI - Comparison between sodium-hydrogen ion and lithium-hydrogen ion exchange in human platelets. AB - The membrane-coupled exchange of Li+ and/or Na+ for H+ was studied in human platelets measuring intracellular pH(pHi) with a fluorescent indicator. A Li(+) containing medium restored the internal pH of preacidified platelets to their prior pHi control value. When Na+ was replaced by Li+, similar steady-state values were attained in this system, although it was transported more slowly. The Km and Vmax were both higher with Na+ than with Li+. Exchanges of Li+ or Na+ with H+ were both blocked by ethylisopropylamiloride (EIPA) achieving half-maximal inhibition at submicromolar concentrations. The efflux Li+ or Na+ and resuspended in a choline medium exhibited an influx of H+ sensitive to EIPA. Thrombin, an activator of Na+/H+ exchange, induced a rapid increase in platelet internal pH in the presence of exogenous Li+. Thus: (1) Li+ can be substituted for Na+ in both the forward and the reverse exchange reaction; (2) Li+, while having a higher affinity than Na+ for the external site of the membrane carrier, has a lower Km and (3) Li+ as well as Na+ exchange are activated by thrombin. PMID- 8218323 TI - Demonstration of two isoforms of the SERCA-2b type Ca2+,Mg(2+)-ATPase in pancreatic endoplasmic reticulum. AB - An antibody raised against a 12 amino acid peptide corresponding to the C terminal sequence of the SERCA-2b Ca2+,Mg(2+)-ATPase precipitated Ca2+,Mg(2+) ATPase activity from pancreatic rough ER. Thapsigargin and vanadate inhibited the activity with the same concentration-dependence as for native ER membranes. Partial purification of Ca2+,Mg(2+)-ATPase using Reactive Dye-agarose affinity chromatography resulted in activation of the enzyme, suggesting the presence of an endogenous inhibitor which was detached by binding to the Reactive Dye. Immunoblots and analysis of immunoprecipitated protein revealed two bands of molecular masses approx. 111 kDa and 97 kDa. It is concluded that pancreatic ER Ca2+,Mg(2+)-ATPase is of the SERCA-2b type and consists of two isoforms. PMID- 8218324 TI - The targeting of immunoliposomes to tumour cells (A431) and the effects of encapsulated methotrexate. AB - Immunoliposomes have been prepared from lipid mixtures of dipalmitoylphosphatidylcholine, wheat germ phosphatidylinositol and a reactive lipid (the m-maleimidobenzoyl-N-hydroxysuccinimide derivative of dipalmitoylphosphatidylethanolamine) which was conjugated to the N-succinimidyl-S acetylthioacetate (SATA) derivative of a monoclonal antibody (H17E2) raised to human placental alkaline phosphatase (PLAP). The immunoliposomes were prepared by the extrusion technique (VETs) and by reverse phase evaporation (REVs) and were found to effectively target to immobilised PLAP and to PLAP or PLAP-like enzyme on the surface of a tumour cell line (A431) using an ELISA and autoradiography. The extent of binding to immobilised PLAP was a function of immunoliposomal lipid concentration, the weight-average number of antibody molecules per liposome (Pw) and the liposome size. The effectiveness of methotrexate-loaded immunoliposomes in inhibiting the proliferation of A431 cells was investigated relative to equivalent levels of the free drug. The immunoliposomes prepared by the extrusion technique (VETs) inhibited growth of A431 cells but had no effect on the growth of a normal human fibroblastic cell line. Immunoliposomes prepared by reverse phase evaporation (REVs) were less effective in inhibiting A431 cell proliferation. The immunoliposomes probably enter the tumour cells largely by receptor-mediated endocytosis although other mechanisms of uptake cannot be excluded. PMID- 8218325 TI - Effect of cerulenin on the synthesis of very-long-chain fatty acids in microsomes from leek seedlings. AB - Cerulenin inhibits the elongation of stearoyl-CoA and eicosanoyl-CoA by microsomes from leek seedlings. The inhibition depends on the cerulenin concentration and affects the biosynthesis of docosanoic and tetracosanoic acids only slightly more than that of eicosanoic acid. A 30-min preincubation of the microsomes with cerulenin allows a quantitative inhibition of the elongation at 50 microM cerulenin (50% inhibition at 15 microM cerulenin). A kinetic study of the elongating activity in the presence or in the absence of the inhibitor suggests that the inhibition is non-competitive. Analysis of the products of the reaction suggests that 3-ketoacyl-CoA synthase is the target of cerulenin. A study of the partial reactions demonstrates that the inhibition affects almost exclusively the condensation step. PMID- 8218326 TI - Optimization of the retention properties of vincristine in liposomal systems. AB - The influence of lipid composition, internal pH and internal buffering capacity on the retention properties of vincristine loaded into large unilamellar vesicle (LUV) systems in response to transmembrane pH gradients has been assessed. It is shown that increasing the (saturated) acyl chain length of the phosphatidylcholine molecule, increasing the internal buffering capacity, and decreasing the internal pH all result in increased drug retention. Further, a study of the pH dependence on the rates of accumulation indicate that uptake proceeds via the neutral form of the vincristine molecule. This uptake is associated with an activation energy of 37 kcal/mol for DSPC/Chol LUVs. It is shown that the major improvement in drug retention in vitro is achieved by employing low initial internal pH values, where 90% retention is obtained over 24 h for an initial internal pH of 2. Improved retention in vivo was also observed where a drug-to-lipid ratio approx. 4-fold greater at 24 h was maintained. PMID- 8218327 TI - Dicarboxylate transport at the vacuolar membrane of the CAM plant Kalanchoe daigremontiana: sensitivity to protein-modifying and sulphydryl reagents. AB - Malate is widespread as a charge-balancing anion in plant vacuoles and plays a central role in nocturnal CO2 assimilation in crassulacean acid metabolism (CAM). To characterize the malate transport system at the vacuolar membrane of CAM plants, tonoplast vesicles were prepared from leaf mesophyll cells of the crassulacean plant Kalanchoe daigremontiana. Dicarboxylate uptake, assayed by a membrane-filtration method using [14C]malate or [14C]succinate, displayed saturation kinetics with apparent Km values of 4.0 mM (malate) and 1.8 mM (succinate); competition experiments indicated that both anions were transported by the same system. Dicarboxylate uptake was stimulated severalfold by activation of the tonoplast H(+)-ATPase or H(+)-PPiase, an effect inhibitable by ionophore. Passive (non-energized) dicarboxylate uptake was sensitive to the sulphydryl reagents N-ethylmaleimide and p-chloromercuribenzene sulphonate, as well as to a range of protein modifiers. In particular, inhibition by pyridoxal phosphate was completely substrate-protectable, and that by phenylglyoxal partially so, thus implicating at least one lysine residue and perhaps also an arginine residue in the substrate-recognition site of the transport protein. The involvement of one or more critical lysine residue was supported by analysis of the initial phase of inhibition by pyridoxal phosphate: this showed pseudo-first-order kinetics with a reaction order of 1.03 +/- 0.13 and a Kd for substrate protection close to the apparent Km for dicarboxylate uptake. PMID- 8218328 TI - The effect of long-chain N-acylethanolamines on some membrane-associated functions of neuroblastoma C1300 N18 cells. AB - As reported earlier (Gulaya, N.M., Vaskovsky, V.E., Vystosky, M.V., Volkov, G.L., Govseeva, N.N. and Artemenko, I.P. (1988) Ukr. Biochim. J. 60, 58-63), N acylphosphatidylethanolamines (NAPE) and products of their catabolism, N acylethanolamines (NAE), are present in the lipids of neuroblastoma C1300 N18 undifferentiated cells. The present paper describes the distribution of NAE added to culture medium of differentiated cells and its effect on the fast sodium channels and some other membrane characteristics. It is shown that NAE inhibits the destroying action of veratridine on membranes. PMID- 8218329 TI - Na+/K+/2Cl- cotransport in medullary thick ascending limb cells: kinetics and bumetanide binding. AB - We examined the properties of Na+/K+/2Cl- cotransport in cultured mouse mTAL cells with respect to its kinetics, the contribution of K/K exchange to K fluxes mediated by the cotransporter, and [3H]bumetanide binding and turnover numbers in media with varying osmolality. The addition of bumetanide, the replacement of external Na+ or the replacement of external Cl- resulted in an almost identical (approx. 50%) decrease in K+ influx, suggesting that Na(+)-dependent, Cl(-) dependent, BS K+ influx was a measure of Na+/K+/2Cl- cotransport. The kinetics of the BS K+ influx revealed a high affinity for external Na+ (apparent Km 7 mM) and external K+ (apparent Km 1.3 mM), but a very low affinity for external Cl- (apparent Km 67 mM with a two-site model). Of interest was the finding that none of the K+ (86Rb+) efflux was sensitive to bumetanide, suggesting the absence of cotransport mediated K/K exchange in this cell type. Specific [3H]bumetanide binding was a saturable function of free bumetanide concentration with a Kd of 0.20 microM and maximum binding (Bmax) of 0.63 pmol/mg, or about 53,000 sites per cell. Simultaneous transport and bumetanide binding assays yielded a turnover number of 255 min-1. The omission of external Na+, K+ or Cl- reduced specific [3H]bumetanide binding to values indistinguishable from zero. Changing medium osmolarity resulted in a co-ordinate change in BS K+ influx and bumetanide binding, with a monotonic increase in both transport and bumetanide binding with increase in osmolality from 200 to 400 mosmol/kg. About 85% of the cotransporter sites were located on the apical side, as in the intact mTAL tubule. The simultaneous measurement of BS ion transport and [3H]bumetanide binding in the mTAL cell may provide valuable insights into the regulation of Na+/K+/2Cl- cotransport in this nephron segment. PMID- 8218330 TI - Plasma membrane vesicles from BHK and HL60 cells treated with merocyanine 540 and iodoacetamide. AB - Treatment of BHK or HL60 cell lines with merocyanine 540 in the presence of the sulphydryl blocker iodoacetamide caused budding of the cell surface to release vesicles about 50-100 nm in diameter which accounted for up to 25% of the total surface membrane lipid. Smaller amounts of vesicular material were released in the presence of fluoride and merocyanine 540. The vesicles had a membrane lipid composition which was characteristic of other purified plasma membranes, with large amounts of sphingomyelin, phosphatidylserine and cholesterol and low proportions of phosphatidylinositol, phosphatidylcholine, triacylglycerol and cholesterol ester. This procedure for the isolation of vesicles should be a general method for the purification of plasma membrane components from a wide range of different cell types. PMID- 8218331 TI - Concerning stimulation by injected fluoroaluminate of the sodium efflux in barnacle muscle fibers. AB - Single barnacle muscle fibers from Balanus nubilus were used primarily to examine the validity of two ideas: first, that the injection of KF stimulates the ouabain insensitive Na+ efflux, and that this action is potentiated by adding AlCl3 (Al) in a low concentration to the solution of KF prior to injection. And second, that the injection of a KF-AlCl3 solution into ouabain-poisoned, K(+/-)-depolarized fibers elicits a stimulatory response resembling that obtained by injecting GTP. The results of this study are as follows: injection of 0.5 M KF into unpoisoned fibers causes a sustained rise in the resting Na+ efflux. However, injection of a 0.5 M KF, 10(-3) M AlCl3 solution leads to a reduced rather than an augmented response. Whereas injection of 0.5 M KF into ouabain-poisoned fibers elicits a marked stimulatory response, the injection of 0.5 M KF, 10(-3) M AlCl3 reduces the remaining Na+ efflux. Injection of KF-AlCl3 in equimolar concentrations, e.g., 0.25 M, elicits a response that is significantly larger than that obtained by injecting 0.25 M KF. A dose-response curve indicates that a 0.2 M solution of fluoroaluminate probably represents an optimal concentration. Injection of 0.3 M KF following peak stimulation by injecting 0.3 M AlCl3 completely reverses this response to Al. In sharp contrast, injection of a 0.3 M KF, 0.3 M AlCl3 mixture following peak stimulation by injecting 0.3 M AlCl3 is ineffective. Injection of KF into ouabain-poisoned, K+ depolarized fibers does not always cause sustained stimulation of the remaining Na+ efflux.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218333 TI - ATP-regulated chloride conductance in endoplasmic reticulum (ER)-enriched pig pancreas microsomes. AB - The Cl- conductance of endoplasmic reticulum-enriched pancreatic microsomes was identified. Its regulation by nucleotides was investigated by measuring the rate of cation ionophore-induced microsome swelling in the presence of an inward Cl- gradient. The conductance was solubilized and reconstituted into liposomes. The Cl- conductance in intact microsomes was inhibited by stilbene (10(-4) M) and indanyloxyacetic acid (10(-5) M) derivatives. ATP increased Cl- conductance with half-maximal stimulation at 8 x 10(-6) M. Other trinucleotides (GTP, CTP and UTP) were without effect at 10(-4) M. The non-hydrolysable analogue of ATP, adenosine 5'-[beta gamma-methylene]triphosphate (AppCH2p) increased Cl- conductance with a potency similar to that of ATP. The same concentration of adenosine 5'-[gamma thio]triphosphate (ATP gamma S) which is a substrate for kinases, had no effect. ATP stimulation of Cl- conductance was inhibited by stilbene derivatives. The data suggest the presence of at least one ATP-binding site, and show that the ATP does not need to be hydrolyzed and that its spatial conformation is important for activating the Cl- conductance. Solubilized microsomal proteins reconstituted into liposomes retained their stilbene-inhibited, ATP-stimulated Cl- conductance. A 167 kDa protein was detected by anti-CFTR antibodies in the intact microsomes, but not in the solubilized proteins. The 64 kDa protein (a component of a ubiquitous Cl- channel) was detected in the both intact and solubilized microsomes. These results suggest that this Cl- conductance is not a CFTR protein. PMID- 8218332 TI - Editing 13C-NMR spectra of membranes. AB - We report the carbon-13 'magic-angle' sample-spinning nuclear magnetic resonance (NMR) spectra of several lipid-water systems, under a variety of radiofrequency excitation conditions. Our results show that complex lipid or membrane spectra can be greatly simplified by using 'spectral editing' techniques. For example, in a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-water mesophase, the glycerol (C-1, C-2 and C-3) carbons are readily distinguished from the headgroup C alpha, C beta and C gamma carbons, on the basis of their mix-time behavior in a cross-polarization (CP) experiment, while in the more complex DMPC/cholesterol water system, many of the more rigid cholesterol carbon resonances can be edited from the phospholipid peaks. In very complex systems, such as human myelin membranes, editing permits the unambiguous observation of the mobile lipid headgroup carbon resonances, as well as the much more rigid sterol ring carbons. We also report the observation of a large differential CP due to C-H vector 'magic-angle' orientational effects in the DMPC/desipramine system. Thus, both motional or orientational reduction of the C-H dipolar interaction can lead to considerable simplifications of complex membrane spectra, and are of interest from both spectral assignment and membrane dynamics aspects. PMID- 8218334 TI - Glucuronidation of all-trans-retinoic acid in liposomal membranes. AB - Retinoyl beta-D-glucuronide is a biologically active metabolite of retinoic acid. The kinetics of UDP-glucuronosyltransferase-catalyzed biosynthesis of retinoyl beta-D-glucuronide was examined in rat liver and intestinal native microsomes incubated with [3H retinoic acid incorporated into liposomes. The product was identified by cochromatography with authentic all-trans retinoyl beta-D glucuronide, by hydrolysis with beta-D-glucuronidase, and by mass spectrometry. In vitamin A-sufficient rats the apparent Km values for all-trans-retinoic acid were 173 microM and 125 microM, and the apparent Vmax, 62 and 41 pmol/min per mg, for small intestinal and liver microsomes, respectively. In vitamin A-deficient rats repleted with all-trans-retinyl acetate, the apparent Km (91 microM) and Vmax (53 pmol/min per mg) for intestinal microsomes were in range of those of vitamin A-sufficient rats. The similarities in the kinetic parameters for UDP glucuronosyltransferase in small intestinal mucosa and liver suggest that the reactions are catalyzed by the same enzyme. In vitamin A-deficient rats given a large amount all-trans-retinoic acid (1.2 mmol/day for 3 days) the apparent Km was 105 microM and Vmax, 127 pmol/min per mg of intestinal microsomal protein. We conclude that the kinetics of intestinal retinoic acid glucuronidation are not characteristic of simple detoxification reactions. Retinoyl glucuronide may be important in mediating retinoic acid metabolism and function. PMID- 8218335 TI - Receptor-operated Ca2+ signaling and crosstalk in stimulus secretion coupling. AB - In the cells of higher eukaryotic organisms, there are several messenger pathways of intracellular signal transduction, such as the inositol 1,4,5 trisphosphate/Ca2+ signal, voltage-dependent and -independent Ca2+ channels, adenylate cyclase/cyclic adenosine 3',5'-monophosphate, guanylate cyclase/cyclic guanosine 3',5'-monophosphate, diacylglycerol/protein kinase C, and growth factors/tyrosine kinase/tyrosine phosphatase. These pathways are present in different cell types and impinge on each other for the modulation of the cell function. Ca2+ is one of the most ubiquitous intracellular messengers mediating transcellular communication in a wide variety of cell types. Over the last decades it has become clear that the activation of many types of cells is accompanied by an increase in cytosolic free Ca2+ concentration ([Ca2+]i) that is thought to play an important part in the sequence of events occurring during cell activation. The Ca2+ signal can be divided into two categories: receptor- and voltage-operated Ca2+ signal. This review describes and integrates some recent views of receptor-operated Ca2+ signaling and crosstalk in the context of stimulus-secretion coupling. PMID- 8218336 TI - Endogenous amino acid transport systems and expression of mammalian amino acid transport proteins in Xenopus oocytes. AB - Oocyte amino acid transport has physiological significance to oocytes and practical importance to molecular biologists and transport physiologists. Expression of heterologous mRNA in Xenopus oocytes is currently being used to help clone cDNAs for amino acid transporters and their effectors. A major question to be resolved in many of these studies is whether the injected mRNA codes for a transporter or an activator of an endogenous system. Nevertheless, the cDNAs of several families of amino acid transporters or their activators appear already to have been cloned. One such transporter is the anion exchanger, band 3, which may also transport glycine and taurine under some important physiological conditions such as hypoosmotic stress. Site-directed mutagenesis of band 3 has already shown that an amino acid residue believed to be at or near the active site nevertheless does not appear to influence Cl- transport in Xenopus oocytes expressing the modified band 3 protein. Continuation of such studies along with examination of transport of all possible substrates of band 3 should yield insight into the relationship between the structure and function of this transporter. Each of three other families not only contains amino acid transporters, but also appears to contain members that serve as transporters of neurotransmitters or their metabolites. Because of the distinct structural differences in the preferred substrates of different transporters within some of these families, elucidation of the tertiary and possibly quaternary structural relationships among the members of such families may reveal transport mechanisms. In addition, the grouping of neurotransmitters or their metabolites according to the family to which their transport systems and transporters belong could yield insight into mechanisms of brain development, function and evolution. Another family of transporters for cationic amino acids also serves, at least in one case, as a viral receptor. Hence, these or other transporters also could conceivably function in eggs as receptors for sperm and, more broadly, in cell cell interactions as well as in amino acid transport. Moreover, a family of apparent amino acid transport activators are homologous to a family of glycosidases, so these activators could also serve to recognize carbohydrate structures on other cells or the extracellular matrix. Some of these activators appear to increase more than one amino acid transport activity in Xenopus oocytes. In other studies, expression of heterologous mRNA in oocytes has led apparently to detection of inhibitors as well as activators of amino acid transport. Some amino acid transport systems also could conceivably contain nucleic acid as well as glycoprotein components.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8218337 TI - Type I receptors for PACAP (a neuropeptide even more important than VIP?). AB - Among vertebrates, there is an extreme conservation in amino acid sequence for the neuropeptide PACAP-38 and its C-terminal shortened derivative PACAP-27. The PACAP gene is assigned to chromosome 18 in man and its organization has been characterized. PACAP-38 and its minor derivative PACAP-27 are widely distributed in the central nervous system. PACAP-38 is particularly abundant in hypothalamus. The mapping of the afferentation and efferentation of PACAP systems are progressively delineated, including a search for the colocalization with other neurotransmitters. In several peripheral organs positive neuronal perikarya and fibers are also seen. PACAP acts through two types of receptors: (1) the highly selective type I that displays a 500 to 2000 selectivity for PACAP-38 and PACAP 27 as compared to VIP; (2) type II is the so-called VIP receptor showing similar high affinity for PACAP-38, PACAP-27 and VIP. It is less selective, therefore, than previously thought. This is why this second receptor, qualifying as an unspecific VIP-PACAP receptor, is hardly considered here. Type I receptors can stimulate two enzymes: the adenylate cyclase and phospholipase C (whose activation leads to the inositol phosphate-cytosolic Ca2+ cascade). This dual coupling may have several distal consequences including on gene expression, cell growth and differentiation. Although a relatively comprehensive spectrum of pharmacological activities has already been established we still need to limit the physiological roles of PACAP as neurotransmitter and/or neuromodulator. Concerning the hypothalamo-pituitary axis, PACAP reduces food intake in mice and raises plasma arginine vasopressin in rat, probably through PACAP-ir neurons in paraventricular and supraoptic nuclei projecting to the neurohypophysis. PACAP originating in the hypothalamus may also be transported to the anterior pituitary through portal vessels. Data on the antehypophysis suggest a role on i.a. reproduction and growth. PACAP stimulates adenylate cyclase and increases [Ca2+] in gonadotropes, somatotropes, and folliculo-stellate cells. It elevates the secretion of alpha-MSH from melanotropes, and that of interleukin-6 from pituitary folliculo-stellate cells. PACAP potentiates the effects of LHRH on LH and FSH secretion. More clearly perhaps, PACAP increases the synthesis of LH, GH, PRL and ACTH after 1-2 days. In human pathology, PACAP-27 and PACAP-38 stimulate adenylate cyclase activity in membranes from 'null'-, gonadotropin-, GH-, and ACTH-producing pituitary adenomas but are inactive in prolactinomas.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8218338 TI - Structure-function relationships of cation binding in the Na+/K(+)-ATPase. PMID- 8218339 TI - Mammalian non-pancreatic phospholipases A2. PMID- 8218340 TI - Luteal phase-characteristic induction of I3SO3-GalCer in human cervical epithelia and uterine endometria, and follicular phase-characteristic formation of a ganglioside-derived negative charge gradient in different regions of fallopian tubes. AB - In a series of experiments on the hormone-dependent molecular alteration in the human genital tract during the menstrual cycle, we focused our attention on a change in the negative charge due to the sulfuric acid- and sialic acid containing glycosphingolipids. Although a ganglioside-derived negative charge was maintained in the cervical epithelia and uterine endometria at a relatively constant concentration throughout the luteal and follicular phases, I3SO3GalCer in both tissues characteristically increased in the luteal phase, indicating that the synthesis of I3SO3-GalCer in both tissues is associated with the menstrual cycle. However, I3SO3-GalCer in mucosae of the fallopian tubes in both phases was present in a concentration similar to that in the uterine endometrium in the luteal phase, and the change in the concentration did not associated with the menstrual cycle. On the other hand, although the concentrations of I3SO3-GalCer and II3NeuAc-LacCer, a major ganglioside, were similar in different regions, that is, the isthmus, ampulla and fimbriae of the fallopian tubes in the luteal phase, II3NeuAc-LacCer was present in a gradually increasing concentration from the isthmus to the fimbriae in the follicular phase, giving a gradually decreasing ratio of I3SO3GalCer to ganglioside from the uterus to the fimbriae. These findings indicate that the metabolism of sulfo- and sialoglycosphingolipids in the human genital tract is strictly controlled by estrogen and progesterone. PMID- 8218341 TI - Hormonal regulation of cholinephosphate cytidylyltransferase in human fetal lung. AB - Cytidylyltransferase (CTP: cholinephosphate cytidylyltransferase, EC 2.7.7.15, CYT) is a regulatory enzyme for synthesis of pulmonary surfactant phosphatidylcholine (PC). The effects of glucocorticoid, T3, and cAMP on CYT activity were studied in explants of human fetal lung (18-22 weeks gestation) cultured for 1-6 days in serum-free medium. Dexamethasone (Dex, 10 nM) treatment for 5 days increased homogenate CYT activity (+115%, P < 0.02) when assayed in the presence of added lipid co-factor (L-alpha-phosphatidylglycerol, PG, 1.1 mM) and tended to increase activity in its absence (+77%, P = 0.12). Cytosolic activity was also significantly elevated in the presence of added co-factor (+124%, P < 0.01), but there was no effect of Dex on microsomal specific activity. Dex increased the recovery of CYT activity in the cytosolic fraction (75% vs. 43% (control) of the homogenate activity), but not in the microsomal, nuclear or mitochondrial fractions. Assayed in the presence of added co-factor, stimulation of CYT by Dex was apparent after 48 h exposure and maximal by 5-6 days exposure to < or = 30 nM concentration. T3 or agents that increase endogenous cAMP stimulated cytosolic activity by 40% and 36-74%, respectively, after 4-6 days exposure, but none produced an additive increase in the presence of Dex. We conclude that stimulation of CYT activity contributes to hormonal induction of surfactant lipids by each of these hormones. Glucocorticoids may increase the amount of CYT enzyme as well as activate the enzyme via increased synthesis of lipid co-factor. PMID- 8218342 TI - cis-9,cis-15-octadecadienoic acid: a novel fatty acid found in higher plants. AB - An unusual fatty acid, cis-9,cis-15-octadecadienoic acid, has been identified in the pulp lipids of mango (Mangifera indica L.) grown in the Philippines. To our knowledge, the occurrence of cis-9,cis-15-octadecadienoic acid in higher plant lipids has not been previously reported. The structure confirmation was based on the results of chromatographic (capillary GC, argentation thin-layer) and spectrometric (GC-MS, infrared, ultraviolet) analysis and chemical treatment. This butylene-interrupted dienoic fatty acid is concentrated in the pulp part of mango fruit and occupies 5.4% of total acyl groups in the pulp lipids; whereas a common octadecadienoic acid, linoleic acid, is a minor component (1.1%) in the same lipids. If a trivial name is desired, it is suggested that cis-9,cis-15 octadecadienoic acid be called "mangiferic" acid. PMID- 8218343 TI - Pyruvate stimulates hormonal induction of lipogenic enzymes in primary cultured rat hepatocytes. AB - Hormonal inductions of lipogenic enzyme activities (fatty acid synthetase, malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) and ATP-citrate lyase) were studied in primary cultured rat hepatocytes. Insulin, triiodothyronine and dexamethasone markedly stimulated the inductions of the enzymes (particularly G6PD and ME) in the presence of pyruvate. Lactate also induced their activities. The activities of these enzymes in the presence of appropriate hormone combinations and a substrate amount of pyruvate were as high as, or higher than those in the liver of rats on high-carbohydrate, low-fat diet. The aldolase and glucokinase activities induced by these hormones were not enhanced by the addition of pyruvate. The induction by pyruvate was inhibited by actinomycin D or cycloheximide. The ATP content of rat hepatocytes was maintained without increase during culture with pyruvate for 6 days. These results indicate that the additions of pyruvate, or its metabolites to cultures of isolated hepatocytes have specific effects on the inductions of certain hepatic enzymes, possibly acting at the level of transcription. Their effects are similar to those of feeding a high-carbohydrate, low-fat diet to intact animals. PMID- 8218344 TI - Studies on the subcellular distribution of 1-O-alkyl-2-acetyl-sn-glycero phosphocholine (PAF) and on the enzymic activities involved in its biosynthesis within the ciliate Tetrahymena pyriformis. AB - The ciliated protozoan Tetrahymena pyriformis contains platelet-activating factor (PAF) as a physiological minor lipid. Its subcellular localization was found as follows: 13.7% in the pellicles, 24.9% in mitochondria, 56.5% in microsomes and 7.1% in the cytosol. Succinate dehydrogenase was used as marker enzyme. PAF remains cell-associated unless bovine serum albumin is included in the extracellular medium. In this case 15% of total PAF, portion comparable to that found in the pellicles, is released. Investigation of the principal enzymic activities involved in PAF formation showed that PAF-acetyltransferase (2.3.167) is totally absent from the protozoan. This means that the 'remodelling' pathway occurring in pro-inflammatory cells does not contribute in PAF formation in our system. A dithiothreitol (DTT)-insensitive CDPcholine phosphocholinetransferase activity involved in PAF biosynthesis is shown for the first time to be responsible for PAF production in T. pyriformis. It uses exogenous alkyl-acetyl glycerol as substrate and is saturated over substrate concentration 250 microM. It can also use endogenous lipids as substrate. It is distributed mainly in mitochondria and microsomes, much less is found in the pellicles and it is totally absent from the cytosol. Its insensitivity to DTT, its selectivity to alkyl-acetyl-G and its different distribution compared to the enzymic activity involved in PC formation (EC 2.7.8.2) suggest that a different enzyme, specific for PAF formation (EC2.7.8.16) via the de novo pathway exists in the protozoan. PMID- 8218345 TI - Effect of development and nutritional state on the uptake, metabolism and release of free and acetyl-L-carnitine by the rodent small intestine. AB - Intestinal carnitine levels and the incorporation and release of exogenous, [14C]carnitine were compared in intestine from adult rat and guinea pig. Total carnitine levels were 4-fold higher in rat as compared to guinea pig intestine. Retention of label was also 4-fold greater, 4 h after placing carnitine (7 nmol) in the lumen. Carnitine was detected in rat chow (64 nmol/g) but not in guinea pig chow. Intestinal carnitine was reduced 2-fold in rats fed a carnitine-free diet for 2 weeks, suggesting the importance of dietary carnitine in determining intestinal carnitine levels. Two conditions where fatty acid oxidation is increased (fasting and suckling) resulted in elevated carnitine levels and retention. In the 3-day fasted guinea pig, intestinal carnitine increased by 40% and retention of a lumenal dose of [14C]carnitine increased about 7-fold after 4 h. During suckling, carnitine levels peaked after 3 days (792 nmol/g) and decreased to near adult levels after 7 days (108 nmol/g). Retention of a lumenal dose of carnitine was greater after 4 h in 1-day old neonatal, than in adult intestine (82% vs. 7% of a 7 nmol dose, respectively). This reflects, in part, the larger intestinal carnitine pool on day 1 (352 nmol/g) than on day 29 (91 nmol/g). The calculated efflux of total intestinal carnitine after 4 h was similar for adults and neonates (72 vs. 58 nmol/g) suggesting that efflux relative to pool size was greater in the adult than in the neonate. Uptake of [14C]acetylcarnitine was similar to [14C]carnitine in 1-day old animals, but was retained to a lesser extent (36% vs. 82%, respectively) after 4 h. The calculated efflux of total intestinal carnitine when acetylcarnitine was the substrate was about 4-fold that when carnitine was the substrate. Incorporation of [14C]carnitine into enterocytes isolated from 3-day old animals was 4-fold greater than into enterocytes isolated from adults (152 vs. 36 pmol/mg protein after 60 min). Active transport of carnitine into enterocytes from neonates, but not from adults is suggested, since labeled free intracellular carnitine reached 4-fold the calculated equilibrium value in neonatal enterocytes, but did not exceed the equilibrium value in adult enterocytes. PMID- 8218346 TI - Arachidonate-containing triacylglycerols: biosynthesis and a lipolytic mechanism for the release and transfer of arachidonate to phospholipids in HL-60 cells. AB - When HL-60 cells are incubated in media containing 10 microM [3H]arachidonic acid the label is immediately incorporated into both triacylglycerols and phospholipids. About one-half of the cellular tritium was associated with triacylglycerols after 2 h of incubation and this [3H]arachidonate was then transferred to phospholipids as soon as the labeled cells were placed in arachidonate-free media. A technique was devised to analyze the stereospecific distribution of [3H]arachidonate at the three sn-positions of glycerol in order to identify the mechanism(s) responsible for the biosynthesis of the labeled triacylglycerols. [3H]Arachidonate was found to be distributed in nearly equal amounts among all three glycerol positions of the triacylglycerols. In addition, analysis of intact triacylglycerols containing [3H]arachidonate revealed that 24% of the tritium eluted from reverse-phase HPLC with triarachidonoylglycerol. Both of these findings would be expected if a significant portion of the arachidonate containing triacylglycerols were synthesized de novo. Homogenates prepared from [3H]arachidonate prelabeled HL-60 cells were capable of hydrolyzing the endogenous [3H]arachidonate-containing triacylglycerols to produce mainly free fatty acids and smaller amounts of monoacylglycerols. The relatively small amount of monoacyl- and diacylglycerols produced by the lipolytic activity of the homogenates indicated that [3H]arachidonate was hydrolyzed from all three sn positions of the [3H]triacylglycerols. This lipase activity had a pH optimum of 4.5 and was associated to a greater extent with the soluble fraction than in the total membrane fraction. Although it is not known whether this lipolytic activity is the same as that expressed in the intact cells, the activity of the cell-free triacylglycerol lipase was of sufficient magnitude to have easily accounted for the decrease in [3H]triacylglycerols that was observed after transfer of the intact HL-60 cells (prelabeled with [3H]arachidonate) to fresh media. The data suggest that transfer of arachidonate from triacylglycerols to phospholipids probably occurs through an acyltransferase utilizing a lysophospholipid and arachidonoyl-CoA. PMID- 8218347 TI - Biosynthesis and shedding of murine lymphoma gangliosides. AB - Ganglioside biosynthesis and subsequent shedding are a potential mechanism contributing to tumor cell escape from the host immune response. As a first step in identifying active molecular species, structural characterization and quantification of the purified individual cellular and shed gangliosides of YAC-1 murine lymphoma cells were undertaken. These studies uncovered three striking changes in ganglioside metabolism in cells passaged in vivo, compared with cells cultured in vitro. (i) Marked inhibition of GalNAcGM1b synthesis: GM1b was present in an equal proportion to its biosynthetic product GalNAcGM1b in vitro, but was present in a 6-fold higher concentration in vivo. (ii) Marked inhibition of NeuGc synthesis: NeuGc, present in vitro in an up to 7-fold higher concentration than its biosynthetic precursor NeuAc, was decreased in relative concentration in vivo (1:1). (iii) Selectivity of shedding: ganglioside shedding in vitro was generalized with respect to both carbohydrate structure and ceramide structure (mainly d18:1-C24:1 and d18:1-C16:0), while in vivo, there was selective shedding of gangliosides containing NeuGc and the shorter chain fatty acid. The reduced synthesis of NeuGc and of GalNAcGM1b in vivo, and the selective shedding of more polar ganglioside species, also in vivo, show that the extracellular environment can markedly affect cellular ganglioside metabolism. PMID- 8218348 TI - Effect of vitamin E on arachidonic acid-release in rat peritoneal macrophages. AB - We have previously reported on suppression of the PGE2 production in PMA- and calcium ionophore A23187-stimulated macrophages isolated from vitamin E-treated rats. To further study the mechanism, we examined the effect of vitamin E on phospholipase A2 activity in both intact macrophages and cell-free homogenates measuring the release of [14C]arachidonic acid. In macrophages from vitamin E treated rats, arachidonic acid release in intact cells as stimulated with PMA and calcium ionophore A23187 was hardly detected. In the cell-free homogenates, increase in phospholipase A2 activity of cytosol and particulate fractions by PMA and A23187 was partially suppressed. In unstimulated macrophages, most of phospholipase A2 was recovered in the cytosol fraction. The partially purified cytosolic phospholipase A2 showed a molecular mass 95 kDa on TSK gel G3000SW gel filtration and on Western blot analysis using anti-rabbit platelet phospholipase A2 monoclonal antibody RHY-5. The activity of cytosolic 95 kDa phospholipase A2 was not inhibited in vitro by vitamin E. From these results, it was suggested that vitamin E needs intact macrophages to suppress arachidonic acid release. PMID- 8218349 TI - Lipoxygenase in soybean seedlings catalyzes the oxygenation of phospholipid and such activity changes after treatment with fungal elicitor. AB - Lipoxygenase (LOX) activities in the crude extracts of soybean cotyledons on phospholipid were measured by a chemiluminescence (CL) assay system. The activity of LOX on phospholipid increased at 6 h after treatment with fungal elicitor, whereas the activity in the control experiment without elicitor treatment declined with incubation. A rise of LOX activity at 6 h incubation is considered to be induced by the elicitor treatment. The LOX fraction obtained from soybean cotyledons at 6 h after elicitation by a DEAE column chromatography was reacted with 1-palmitoyl-2-linoleoyl-phosphatidylcholine substrate. The reaction product was analyzed by HPLC equipped in series with a UV (205 nm) and a CL detector. Most of the substrate was converted to a hydroperoxy compound. By the CL-HPLC analysis after transesterification of reaction product and by mass spectrum of the trimethylsilyl derivative after reduction of methyl ester confirmed that the linoleic moiety was subjected to oxygenation at 13-position. The steric analysis of menthoxyacetyl derivative prepared from hydroxy fatty acid methyl ester showed S configuration. These findings suggest that the oxygenation of membrane lipids in biological plant tissues might be initiated by the direct action of LOX. PMID- 8218350 TI - Effects of selenium supplement on the de novo biosynthesis of glycerolipids in the isolated rat heart. AB - The effect of selenium supplement on glycerolipid biosynthesis in the isolated rat heart was investigated. Selenium was administered to the rat by intraperitoneal injection of 4.33 mumol/kg per day for 3 consecutive days. Animals administered with an equal volume of saline were used as controls. Hearts from both animal groups were perfused in Krebs-Henseleit buffer containing labelled glycerol. Subsequent to perfusion, the radioactivity associated with each glycerolipid group was determined. Selenium supplement caused elevations in the labelling of phosphatidic acid and phosphatidylcholine but not in other phospholipids, diacylglycerol or triacylglycerol. The mechanisms for the enhancement of labelling into phosphatidic acid and phosphatidylcholine were examined. The activity of the enzymes responsible for the synthesis of phosphatidic acid in the rat heart was not changed by selenium supplement. However, a 51% increase in the acyl-CoA level was detected which might account for the elevated labelling of phosphatidic acid in the selenium supplemented animal. The 2-fold increase in the activity of CDPcholine:diacylglycerol cholinephosphotransferase might also account for the increase in the labelling of phosphatidylcholine in the heart of the selenium-supplemented rat. It is clear from this study that selenium plays a regulatory role in the control of cellular lipid metabolism. PMID- 8218351 TI - Type II phospholipase A2 in human gestational tissues: extractable immuno- and enzymatic activity in fetal membranes. AB - In this study, we have established the presence of immunoreactive (ir) Type II PLA2 in human amnion and choriodecidua obtained from women at term prior to the onset of labour. The content of irType II PLA2 present in 1 M NaCl extracts of choriodecidua and amnion averaged 3.5 +/- 3.1 and 10.6 +/- 5.2 ng/mg tissue protein (n = 3), respectively. PLA2 enzymatic activity present in the same tissues averaged 1.3 +/- 0.2 and 1.9 +/- 0.7 nmol phosphatidylethanolamine (PE) hydrolysed/mg tissue protein per h (n = 3), respectively. To allow intra-patient comparison of the relative distribution in gestational tissues, irType II PLA2 and PLA2 enzymatic activity was also determined in placenta obtained from the same group of women, and averaged 26.0 +/- 7.0 ng/mg tissue protein and 3.5 +/- 1.0 nmol PE hydrolysed/mg protein per h (n = 3), respectively. As has been previously reported for human placenta, the recovery of Type II PLA2 and PLA2 enzymatic activity from amnion and choriodecidua was increased between 16- and 25 fold when tissues were homogenized in high-ionic strength media (i.e., 10% (w/v) ammonium sulphate or 1 M NaCl) compared with that recovered when tissues were homogenized in low-ionic strength media (i.e., 0.32 M sucrose-20 mM Hepes). The data obtained represent the first quantitative estimates of immunoreactive Type II PLA2 in human amnion and choriodecidua, and support the conclusion that previous analyses of the PLA2 enzymatic activity present in gestational tissues have essentially excluded the contribution made by this PLA2 isozyme to net enzymatic activity. We suggest that this isozyme represents a major component of the PLA2 enzymatic activity present in human gestational tissues at term and that it contributes significantly to the phospholipid metabolism and arachidonic acid release which occurs during late pregnancy and at the time of labour. PMID- 8218352 TI - Regulation of hsp70 induction in thermotolerant HeLa cells. AB - Upon exposure to heat shock, non-thermotolerant (NT) HeLa cells transiently synthesize a large amount of 70-kDa heat-shock protein (hsp70), whereas thermotolerant (TT) cells synthesize a small amount of hsp70. When the hsp70 mRNA of HeLa cells was analyzed, it became apparent that hsp70 mRNA in TT cells did not increase following heat shock, whereas hsp70 mRNA in NT cells did increase dramatically. A further analysis of the activation of the heat-shock transcription factor (HSF) showed that significant activation of HSF was observed immediately after heat shock in both NT and TT cells. However, activated HSF was rapidly repressed in the TT cells, but not in the NT cells. Thus, the decreased induction of hsp70 synthesis observed in the TT HeLa cells may be due to the immediate repression of activated cellular HSF, which probably results in the reduced induction of hsp70 mRNA. The hsp70 content in the TT cells was usually higher than in the NT cells. However, after heat-shock treatment, the hsp70 content of the NT cells increased to nearly the level of the TT cells concomitant with the repression of hsp70 synthesis. The association of activated HSF with hsp70 was observed in both NT and TT cells, and the amount of HSF-hsp70 complex within the cell increased in proportion to the increase in hsp70 in the cells. These findings strongly suggest that the activity of HSF is negatively regulated by the intracellular content of hsp70 in these cells. Furthermore, in vitro experiments on the activation of HSF suggest that HSFs of NT and TT cells may have different properties, or an unknown factor may exist which regulates HSF activation in these cells. PMID- 8218353 TI - The isolation from a unicellular organism, Dictyostelium discoideum, of a highly related cdc2 gene with characteristics of the PCTAIRE subfamily. AB - It has been suggested that cell-type determination in Dictyostelium discoideum is dependent on the position of a cell in the cell cycle at the time of starvation. In order to understand the molecular basis of this phenomenon, we initiated studies on the cell cycle and have recently described the isolation of a Dictyostelium gene encoding a homolog of the Cdc2 kinase. We have been unable to isolate additional cdc2 genes from Dictyostelium using polymerase chain reaction technology, but have isolated a gene that is highly related to cdc2. The encoded product is a protein of 33 kDa that shares over 60% identity to the cell-cycle dependent Cdc2 kinases. However, despite this high level of identity, the gene is not capable of complementing the temperature-sensitive cdc28 mutant of Saccharomyces cerevisiae. Furthermore, the gene product shares some characteristics with the recently described PCTAIRE proteins; it contains a PCTAIRE motif instead of the Cdc2 kinase conserved PSTAIRE sequence, it does not possess the conserved GDSEID sequence that is involved in the activation of the enzyme and it has a Ser in the position equivalent to Thr-161. However, the Dictyostelium protein exhibits a slightly higher level of identity to the Cdc2 kinases than to the PCTAIRE proteins and is smaller than any of the PCTAIRE proteins thus far identified. Since the gene product has characteristics of both Cdc2 kinases and PCTAIRE proteins we have designated the gene product Crp (Cdc2 Related PCTAIRE) kinase. The gene is expressed as two transcripts of 1.5 and 1.8 kb and the expression is developmentally regulated with low levels of mRNA in vegetative cells and significantly higher levels throughout the remainder of the differentiation process. These results suggest the possibility that the gene product is involved in Dictyostelium differentiation rather than growth. This report is the first evidence for a highly-related cdc2 gene in unicellular eukaryote. It also demonstrates for the first time that a unicellular eukaryote expresses a protein containing the PCTAIRE sequence. PMID- 8218354 TI - Fatty acid modulation of cytokine release from human monocytic cells. AB - The effect of individual fatty acids on the release of interleukin-1-like (IL-1 like) cytokine activity was investigated on human monocytic cells, primarily the cell line U937 and also peripheral blood monocytes. IL-1-like bioactivity was estimated by assessing the effect of supernatants from monocytic cells on the proliferation of thymocytes as measured by [3H]thymidine incorporation into the acid insoluble fraction of the thymocytes. A pronounced concentration-dependent increase (in the range 1-100 microM) in the release of IL-1-like activity was observed with arachidonic acid, dihomo-gamma-linolenic acid (DGLA) and eicosapentaenoic acid (EPA) in absence and presence of bacterial endotoxin (LPS). A much less pronounced concentration-dependent increase in the release of IL-1 like activity was observed with oleic acid and linoleic acid had only a small effect at 100 microM. The potencies of each fatty for this effect using the EC50 concentrations were arachidonic acid > EPA > or = DGLA > linoleic acid > oleic acid with palmitic acid having no effect. The IL-1-like activity was confirmed by the attenuation of the monocytic-cell-supernatant-induced increase in thymocyte proliferation by anti-IL-1 beta antiserum. An increase in the release of anti-IL 1 beta-antiserum-precipitable radioactivity from U937 cells prelabelled with [35S]methionine then incubated with fatty acids in the presence of LPS further confirmed that IL-1 release was increased. Arachidonic acid and EPA also increased the release of IL-1-like activity from peripheral blood monocytes demonstrating that normal monocytes can respond in a similar manner and that this effect of the fatty acids is not restricted to the U937 cell line. PMID- 8218355 TI - Primed pentose cycle activity supports production and elimination of superoxide anion in Kupffer cells from rats treated with endotoxin in vivo. AB - Glucose use and pentose cycle activity were determined in freshly isolated rat Kupffer cells 3 h after an i.v. injection of Escherichia coli endotoxin (0.1 mg/kg body weight), by using [1-14C], [6-14C] and [2-3H]glucose. Endotoxin treatment in vivo caused a 5-fold increase in the basal glucose uptake in Kupffer cells. Pentose cycle activity was elevated from 8.7 to 13.6 nmol/h per 10(7) cells after endotoxin. In vitro treatment of the cells from saline- and endotoxin treated animals with phorbol ester (10(-6) M) increased pentose cycle activity 2 fold and 8-fold, respectively. Phorbol ester caused a 50% increase in glucose uptake in both groups. t-Butyl hydroperoxide (0.5 mM) caused a similar increase in pentose cycle activity as phorbol ester. Glucose oxidation in the Krebs cycle was also doubled after endotoxin. KC from endotoxin-treated animals produced O2- spontaneously, and were primed to produce additional large amounts of O2- upon phorbol ester treatment. Addition of t-butyl hydroperoxide inhibited O2- production by Kupffer cells. Depletion of glutathione by N-ethylmaleimide (0.1 mM), or inhibition of NADPH oxidase by diphenyliodonium (0.1 mM) inhibited both the pentose cycle activity and the O2- production. Increasing the concentration of exogenous glucose in the cell medium elevated the glycolytic rate, while pentose cycle flux was not affected either under basal conditions or following subsequent challenges by phorbol ester or t-butyl hydroperoxide. Our data suggest that the endotoxin-induced elevated glucose use in Kupffer cells is accompanied by a primed state of the pentose cycle. This condition supports superoxide and macromolecule synthesis and could also represent a potentiated protective mechanism against oxidative cellular injury during bacterial infections. PMID- 8218356 TI - Effects of osmotic stress and growth stage on cellular pH and polyphosphate metabolism in Neurospora crassa as studied by 31P nuclear magnetic resonance spectroscopy. AB - High-resolution 31P-NMR was employed to investigate the effects of growth stage and environmental osmolarity on changes of polyphosphate metabolism and intracellular pH in intact Neurospora crassa cells. Our study showed that changes of these parameters were growth-dependent. The ratio of polyphosphate to orthophosphate in vacuoles increased from 2.4 to 13.5 in N. crassa as cells grew from early log phase to stationary phase. Cytoplasmic pH and vacuolar pH changed, respectively, from 6.91 and 6.49 in early log phase cells to 7.25 and 6.84 in stationary phase cells. Hypoosmotic shock of N. crassa produced growth-dependent changes including: (i) a rapid hydrolysis of polyphosphate with a concomitant increase in the concentration of the cytoplasmic phosphate, (ii) an increase in cytoplasmic pH, and (iii) an increase in vacuolar pH. Early log phase cells produced the most dramatic response whereas the stationary phase cells appeared to be recalcitrant to the osmotic stress. Thus, 95% and 60% of polyphosphate in the early log phase and mid-log phase cells, respectively, disappeared in response to hypoosmotic shock, but little or no hydrolysis of polyphosphate occurred in stationary cells. The cytoplasmic pH and the vacuolar pH increased in response to hypoosmotic shock by 0.4 and 0.53 unit, respectively, in early log phase cells; and by 0.22 and 0.27 unit, respectively, in the mid-log phase cells. In contrast, hypoosmotic shock of the stationary phase cells did not cause any change in intracellular pH. The osmotic stress-induced polyphosphate hydrolysis and pH changes in early log and mid-log phase cells were reversible, suggesting that these changes were related environment osmolarity. Addition of polyamines or basic amino acids which are known to be sequestered in vacuoles did not effect polyphosphate metabolism. PMID- 8218357 TI - Interaction of avidin-carrying red blood cells with nucleated cells. AB - In vivo application of red blood cells (RBC) modified with avidin-biotin complex has been suggested recently for various purposes. However, avidin attachment to RBC alters their biocompatibility. Thus, it has been described that avidin carrying biotinylated RBC were lysed by the complement. In the present work interaction between avidin-carrying RBC and nucleated cells has been examined. It was found that attachment of avidin, but not streptavidin, to RBC led to binding of avidin-carrying RBC to nucleated cells. Adhesiveness of nucleated cells for avidin-carrying RBC varied for different types of nucleated cells. The strongest adhesion was observed with human fibroblasts and rat Kupffer cells, while rat liver endothelial cells were practically non-adhesive for avidin-carrying RBC of corresponding species. In contrast with avidin (streptavidin)-induced lysis by the complement, avidin-induced adhesion was independent of temperature, the presence of divalent ions and mode of avidin attachment. Polyanions (dextran sulphate and heparin) efficiently inhibited the adhesion presumably due to interaction with the membrane-bound avidin. Polyanions to a much lesser extent inhibited lysis of avidin-carrying RBC, which might be a result of their interaction with the complement components. Polycations also blocked adhesion of avidin-carrying RBC to nucleated cells, presumably due to interaction with negatively charged cell-surface components. Therefore, attachment of avidin to RBC alters their biocompatibility, due to both high positive charge of avidin and the cross-linking of biotinylated membrane proteins. PMID- 8218358 TI - Coating particles with a block co-polymer (poloxamine-908) suppresses opsonization but permits the activity of dysopsonins in the serum. AB - The surfaces of polystyrene microspheres (60 nm in diameter) and colloidal gold particles (17 nm in diameter) were coated with a polyoxyethylene (POE)/polyoxypropylene (POP) block co-polymer; poloxamine-908. The polymer adsorb strongly to the microspheres via its relatively hydrophobic POP segments. This leaves the POE chains in a mobile state as they extend outward from the surface and thereby provide stability to the particle suspension by suppressing aggregation. The blood clearance and biodistribution of uncoated vs. poloxamine 908-coated 125I-labelled polystyrene microspheres were compared 1 h after intravenous administration into rats. Poloxamine coating dramatically reduced liver accumulation of microspheres and kept them within the systemic circulation. These observations were further confirmed by electron microscopy, demonstrating that Kupffer cells were loaded with uncoated latex but had ingested few if any of the poloxamine-908-coated particles. The interaction of uncoated and poloxamine coated gold particles with freshly isolated rat liver sinusoidal cells was examined by electron microscopy. The accumulation in Kupffer cells of gold particles after opsonization with autologous plasma was in accordance with previous observations where the dominant opsonizing activity had been identified as fibronectin. In contrast, coating of gold particles with poloxamine-908 prior to plasma opsonization prevented the adsorption of fibronectin onto their surface. Simultaneously, Kupffer cells failed to recognize poloxamine-908-coated gold particles before and after opsonization. Unlike Kupffer cells, liver endothelial cells endocytosed poloxamine-908-coated gold particles prior to opsonization but failed to recognize them after the opsonization process. This was taken as an indication of the presence of dysopsonic activity in plasma. This dysopsonic activity was studied using polystyrene latex microspheres, where the uptake of such particles by phagocytes is known to be independent of opsonization. The coating of 125I-labelled polystyrene microspheres with poloxamine-908 dramatically reduced their interaction with liver sinusoidal cells. This interaction was further reduced in the presence of either autologous plasma or serum. A heat-stable (60 degrees C for 15 min) serum component of molecular mass > 100 kDa was found to mediate this suppressive effect. Thus, we demonstrate that organ-specific receptors, opsonin activities and plasma dysopsonins regulate the in vivo clearance of particulate materials from the circulation. Poloxamine-908 coating modulates particle clearance by effectively blocking opsonization but still allowing for dysopsonization. PMID- 8218360 TI - Decrease in the phosphotyrosine phosphatase activity in the plasma membrane of human neutrophils on stimulation by phorbol 12-myristate 13-acetate. AB - Phorbol 12-myristate 13-acetate (PMA) induced a decrease in the phosphotyrosine phosphatase (PTPase) activity in human neurophils. The decrease in the activity induced by PMA was blocked by the treatment of the cells with staurosporine, indicating that protein kinase C is involved in the decrease. The PTPase activity was localized in the plasma membrane. The activity in the membrane with the optimum pH at 5.5 had a Km value for phosphotyrosine of 2.2 mM and Vmax of 2.0 mumol/min per mg of protein. No activity was observed against phosphoserine and phosphothreonine. Vanadate, molybdate, zinc and a sulfhydryl reagent, p chloromercuribenzenesulphonic acid, inhibited the PTPase. The PMA-induced decrease in activity was almost completely recovered by treatment of the plasma membrane with Triton X-100 at low concentrations which did not solubilize the activity from the membrane. When the plasma membrane was treated with trypsin, the PTPase of the membrane from PMA-treated cells was mostly protected from the proteinase attack while that from the resting cells was not protected. Pretreatment of the plasma membrane with Triton X-100 enabled trypsin to gain access to all the PTPase in the membrane from both PMA-treated and resting cells. The PMA treatment affected neither subcellular localization of the PTPase nor the orientation of the plasma membrane vesicles. These findings suggest that conformational changes of the enzyme induced by PMA result in the decrease in PTPase activity. PMID- 8218359 TI - Na+ and K+ transport by 4-chlorophenylurethane-monensin in Enterococcus hirae de energized and energized cells studied by 23Na-NMR and K+ atomic absorption. AB - Na+ and K+ movements induced by 4-chlorophenylurethane-monensin, which presents an inverted ion selectivity (K+ > Na+) in model systems compared with monensin, were followed on Enterococcus hirae cells by 23Na-NMR and K+ atomic absorption. For de-energized cells, the urethane derivative is much more selective for K+ than monensin, but only at low concentrations (10(-3)-10(-4) mM). For higher concentrations, as previously shown for monensin, the sodium and potassium movements are driven by the ion gradients present. On energized cells, both K+ and Na+ gradients were highly perturbed, and this can be related to the higher toxicity in mice and bacteria for this derivative. PMID- 8218361 TI - Comparison of parathyroid hormone receptors in rat osteosarcoma cells and kidney. AB - Parathyroid hormone/parathyroid-hormone-related peptide (PTH/PTHrP) receptors have been characterized with chicken parathyroid hormone related protein [Tyr36]chPTHrP(1-36)amide (chPTHrP(1-36)) as radioligand in rat UMR-106 osteosarcoma (UMR) cells and in rat renal cortical membranes (RCM). Binding of 125 pM [125I][Tyr36]chPTHrP(1-36) was displaced by chPTHrP(1-36) with ID50 values of 2.6 +/- 0.22 nM (mean +/- S.E.) and 0.9 +/- 0.03 nM in UMR cells and RCM, respectively. ID50 values in membranes from UMR cells and RCM were the same in the presence and absence of 10 microM guanosine-5'-O-(3-thiotriphosphate). Rat [Nle8,18] PTH(1-34) was 5-fold more potent than chPTHrP(1-36) in RCM, but not in UMR cells. Hill coefficients derived from binding inhibition were 0.93 and 0.35 in UMR and RCM, respectively. For affinity labeling, N-hydroxysuccinimidyl-4 azidobenzoate-modified [125I]chPTHrP(1-36) was used. Specifically-labeled PTH/PTHrP-binding proteins had a molecular mass of 83 kDa in UMR cells and RCM. Treatment with N-endoglycosidases lowered the molecular mass of chPTHrP binding proteins to 54 kDa in UMR and RCM. In conclusion, skeletal UMR-106 cells and renal cortical membranes of the rat reveal PTH/PTHrP receptors with no apparent tissue specific differences in molecular mass of the polypeptide backbone and polysaccharide chains. Higher affinity of rat PTH(1-34) binding and lower Hill coefficients in kidney compared to bone are consistent with tissue specific receptor-ligand interactions. PMID- 8218363 TI - Distribution and relative levels of expression of the phosphoinositidase-C-linked G-proteins Gq alpha and G11 alpha: absence of G11 alpha in human platelets and haemopoietically derived cell lines. AB - Membranes of a variety of clonal cell lines, including neuroblastoma x glioma hybrid NG108-15, glioma C6, Rat 1 and CHO fibroblasts and the pituitary-derived cell lines alpha T3 and GH3 were immunoblotted with an antiserum (CQ) raised against a synthetic peptide corresponding to the C-terminal decapeptide of the alpha subunits of the phosphoinositidase-C-linked G-proteins Gq and G11. In SDS PAGE conditions able to resolve these two polypeptides, direct evidence was obtained for co-expression of these two G-proteins in all of the above cell lines. The ratio of these two G-proteins varied substantially (alpha 11/alpha q = 0.25-2.5) between the cell lines. In human platelets and in a range of haemopoietically derived human cell lines including U937 (monoblasts), Raji (Burkitts lymphoma) and Jurkat (mature T cell) expression of G11 alpha was not detected. This was not due to the inability of the antiserum to identify human G11 alpha as other human cell lines co-expressed both G-proteins. A third, unidentified CQ reactive polypeptide of similar mobility was resolved and present in all cell lines examined. PMID- 8218362 TI - Retinoic acid stimulates the protein kinase C pathway before activation of its beta-nuclear receptor during human teratocarcinoma differentiation. AB - We previously reported that protein kinase C (PKC) stimulation through phorbol ester (TPA) treatment enhances the effects of all-trans retinoic acid (RA) on immunophenotypic differentiation and RA nuclear receptor (RAR) activation in the multipotential human teratocarcinoma (TC) cell line NTera-2/clone D1 (abbreviated NT2/D1). This study extends prior work in NT2/D1 cells by demonstrating that PKC pathway activation is an early effect of RA treatment which regulates RAR transcriptional activity. RA activated the PKC pathway prior to induction of RAR beta expression at 6 h, which is an established early marker of RAR activation in NT2/D1 cells. RA caused a transient 1.3-fold increase in intracellular diacylglycerol (DG) at 2 min and a translocation of the gamma isozyme of PKC (PKC gamma) within 5 min. Transient co-transfection studies provided evidence that PKC pathway activation plays a role in the regulation of RAR-beta expression. In these studies a constitutively active PKC-gamma augmented the RA-mediated transactivation of a luciferase reporter containing the native RAR-beta promoter which has a retinoic-acid-response element (RARE). These findings reveal that PKC pathway activation is an early step in RA-mediated human TC differentiation and that PKC-gamma can potentiate the effects of RA on RAR transcriptional activation. PMID- 8218364 TI - Activation of the respiratory burst and tyrosine phosphorylation of proteins in human neutrophils: no direct relationship and involvement of protein kinase C dependent and -independent signaling pathways. AB - Human neutrophils maximally stimulated with the optimal concentration (100 ng/ml) of phorbol myristate acetate (PMA), a direct activator of protein kinase C (PKC), for 5 min at 37 degrees C did not respond with superoxide (O2-) release to the later addition of PMA itself or the Ca2+ ionophore ionomycin. However, these cells did respond with enhanced release of O2- to the later addition of N-formyl methionyl-leucyl-phenylalanine (FMLP) or concanavalin A (Con A). In these PMA pretreated cells, an increase in cytoplasmic free Ca2+ ([Ca2+]i) induced by ionomycin was unaffected, whereas that induced by FMLP was inhibited by 50-60% and that induced by Con A was completely abolished. A 42-kDa protein was predominantly and consistently tyrosine-phosphorylated by FMLP, PMA and ionomycin with the different kinetics according to the stimuli. The dose-response curves showed that tyrosine phosphorylation and O2- release were stimulated in parallel by PMA, whereas tyrosine phosphorylation and an increase in [Ca2+]i, but not O2- release, were stimulated in parallel by FMLP or ionomycin. The potency of inducing tyrosine phosphorylation was ionomycin > FMLP = PMA, whereas the potency of triggering of O2- release was PMA > ionomycin = FMLP. UCN-01, a PKC inhibitor, inhibited O2- release and tyrosine phosphorylation induced by PMA, but not by FMLP or ionomycin. In contrast, pertussis toxin inhibited O2- release and tyrosine phosphorylation induced by FMLP, but not by PMA. Tyrosine kinase inhibitors (erbstatin and genistein) inhibited O2- release induced by FMLP, but not by PMA. However, both tyrosine kinase inhibitors did not impair FMLP- or PMA induced tyrosine phosphorylation of a 42-kDa protein. Increased tyrosine phosphorylation of a 42-kDa protein was also detected in immature myeloid cells (HL-60 cells) stimulated by PMA, but not by ionomycin. These findings suggest that FMLP and Con A trigger the respiratory burst in human neutrophils by activating the definite pathway which include other signals than activation of PKC and an increase in [Ca2+]i; tyrosine phosphorylation of a 42-kDa protein is induced by the PKC-dependent and independent mechanisms according to the stimuli, and the PKC-independent and ionomycin-sensitive mechanism is inoperative in HL-60 cells; and tyrosine phosphorylation of a 42-kDa protein is unlikely to be causally related to activation of the respiratory burst. PMID- 8218365 TI - Several routes of activation of the potassium uptake system of yeast. AB - K+ uptake in yeast is activated by glucose and other fermentable sugars, and by cytoplasmic acidification. In sugar kinase mutants, fermentable sugars and 2 deoxyglucose produced activation if the sugar could be phosphorylated, indicating that phosphorylation of the sugar is sufficient to trigger the activating pathway. Activation by cytoplasmic acidification was mimicked by neomycin, suggesting that a phosphatidylinositol-type pathway could be involved. PMID- 8218366 TI - Calponin phosphorylation does not accompany contraction of various smooth muscles. AB - Calponin phosphorylation was quantitated in 32P-labeled porcine arterial, uterine, tracheal, stomach and bladder smooth muscles. The negligible amount of 0.003-0.008 mol [32P]phosphate/mol calponin in resting muscles did not increase upon contraction induced by various agents, under conditions when myosin light chain phosphorylation increased several-fold. The results indicate no involvement of calponin phosphorylation is smooth-muscle contraction. PMID- 8218367 TI - pH-dependent binding of chromogranin B and secretory vesicle matrix proteins to the vesicle membrane. AB - Contrary to the notion that the soluble intravesicular matrix proteins of the secretory vesicles of adrenal medullary chromaffin cells freely float in the vesicle, several vesicle matrix proteins of the secretory vesicles, including chromogranins A and B, bound to the vesicle membrane at intravesicular pH (5.5) and were freed from it when the pH was raised to a near physiological pH (7.5). Estimation of the fraction of vesicle matrix proteins that might remain bound to the vesicle membrane in the vesicle suggested that the majority (> 50-80%) of chromogranins A and B, as well as several other proteins, will stay bound to the membrane in the vesicle. Comparison of the amino-acid sequences of chromogranins A and B revealed two highly conserved regions, i.e., one near the N-terminus and the other being the C-terminal region. Since it has been demonstrated with chromogranin A that the conserved near N-terminal region of chromogranin A exhibited the pH-dependent membrane-binding activity (Yoo, S. H. (1993) Biophys. J., 64, A195), the same region in chromogranin B (residues 17-36) was tested using a synthetic chromogranin B peptide, and found to exhibit the pH-dependent membrane-binding activity. The pH-dependent binding of the matrix proteins at pH 5.5 and the automatic untethering at a physiological pH accord well with the rapid release and circulation of the vesicular contents in the bloodstream. PMID- 8218368 TI - Respiratory burst reaction changes with age in rat peritoneal macrophages. AB - The respiratory burst reaction, estimated as O2.- production, has been studied in rat peritoneal macrophages of different age (3, 12 and 24 months). To stimulate NADPH oxidase, the enzyme responsible for the respiratory burst, various stimuli that act in different ways have been used: PMA (phorbol myristate acetate), Con-A (concanavalin A) and N-FMLP (N-formyl-methionyl-leucyl-phenylalanine). All produced a decrease in response with age, with that from PMA being the greatest. The PMA-induced decrease in the O2.- production may be related to the inactivation of NADPH-producing enzymes such as glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase that we have found with age. Glutathione reductase, an enzyme that participates in the maintenance of the redox status in the cell, also showed an age-related decrease. Enzymes that participate in oxygen species scavenging, such as glutathione peroxidase and Cu/Zn superoxide dismutase, did not change with age, although an age-related decrease in catalase activity was found. PMID- 8218369 TI - Effects on cultured mammalian cells of myotoxin III, a phospholipase A2 isolated from Bothrops asper (terciopelo) venom. AB - Myotoxin III (MT-III), a myotoxic phospholipase A2 from Bothrops asper, was studied with respect to interactions with cultured mammalian cells and red blood cells. Tests of the cytopathogenic effect of MT-III on different cell lines indicated that rat skeletal muscle L6 myoblasts were more sensitive to the toxin than chinese hamster ovary cells, human lung fibroblasts, mouse adrenal tumour cells and rat intestinal epithelial cells. Specific plasma-membrane permeabilization was assayed as release of a cytosolic [3H]uridine nucleotide marker from toxin-treated L6 cells. A dose- and time-related membrane permeabilization was induced at 37 degrees C, but not at 0 degree C. A half maximal effect was obtained after 20 min. 30 micrograms/ml MT-III induced 50% marker release in 1 h, and the effect was not reversed by post-incubation for up to 48 h in toxin-free medium. The membrane permeabilization in L6 cells did not seem to require cellular internalisation of the toxin. The catalytic site of the toxin was inactivated by alkylation with p-bromophenacyl bromide (BPB). This treatment abolished the toxin's specific PLA2 activity, as assayed in vitro, and reduced the PLA2 activity on the myoblast membrane by more than 95%, as measured by release of [14C]arachidonic acid from prelabelled cells. However, the membrane permeabilizing effect (release of cytosolic marker) was reduced only by 70% upon modification with BPB. We also report that MT-III is not directly haemolytic, and one reason for this is the inability of the toxin to associate with the membranes of human or mouse erythrocytes. Taken together, the data suggest that MT-III at 37 degrees C binds to and penetrates the plasma membrane of cultured myoblasts, thereby inducing a rapid, direct and irreversible membrane permeabilization. This effect apparently depends in part on the PLA2 activity of the toxin and in part on a molecular region which is separate from the catalytic site. PMID- 8218370 TI - Regulation of delta protein kinase C during rat ovarian differentiation. AB - Studies were undertaken to classify protein kinase C (PKC) forms present in rat corpora lutea and to begin to evaluate their regulation during ovarian differentiation. Hydroxyapatite (HAP) column chromatography of rat luteal tissue revealed the presence of multiple forms of PKC (alpha, beta, delta, zeta). Identification of the PKC isoforms was based upon elution positions from HAP column chromatography and immunoreactivity. The delta PKC isoform was identified as the major Ca(2+)-independent form of PKC present in rat luteal tissue. The Ca(2+)-independent, lipid-dependent phosphorylation of the 80-kDa delta PKC was readily detectable in soluble luteal extracts and was shown to reflect autophosphorylation of delta PKC. To evaluate the regulation of PKC isoforms during ovarian differentiation, PKC protein levels were compared between preovulatory follicle-enriched ovaries and corpora lutea obtained on day 16 of pregnancy. Levels of delta PKC protein were greatly elevated in corpora lutea compared to levels in preovulatory follicles. In contrast, levels of alpha and beta PKC protein remained constant while levels of zeta PKC were slightly higher in the follicular than the luteal extract. Levels of delta PKC mRNA were also higher in corpora lutea than in preovulatory follicles. These results are the first to demonstrate the physiological regulation of delta PKC with follicular differentiation into corpora lutea and implicate a role for this prominent PKC form in the corpus luteum during pregnancy. PMID- 8218371 TI - Differential effects of calyculin A and okadaic acid on the glucose-induced regulation of glycogen synthase and phosphorylase activities in cultured hepatocytes. AB - The effects of the phosphatase inhibitors calyculin A and okadaic acid were investigated to determine the roles of protein phosphatases type 1 and 2A in the regulation of the activities of glycogen synthase and phosphorylase by glucose in a primary culture of hepatocytes. Glycogen synthesis, as measured by the incorporation of labelled glucose into glycogen, was inhibited in a dose dependent manner by calyculin A (IC50 = 2.2 nM) and okadaic acid with (IC50 = 14 nM). Glucose-induced activation of glycogen synthase was inhibited by calyculin A and okadaic acid with IC50 values of 3.7 nM and 90 nM, respectively. Phosphorylase was simultaneously activated by these inhibitors with calyculin A again being more active (P < 0.001) than okadaic acid. The differing potencies (P < 0.001) of these inhibitors on the activities of glycogen synthase and phosphorylase were also observed with varying concentrations of glucose (5.6-60 mM) in the medium and at different incubation periods upto 120 min. It has been previously shown that both inhibitors inhibit protein phosphatase-2A with equal potency and calyculin A is a more potent inhibitor of protein phosphatase-1 than okadaic acid. Heat- and proteinase-treated cytosolic fractions from hepatocytes incubated with calyculin A and okadaic acid showed similar differential inhibitory activities towards purified types 1 and 2-A protein phosphatases. Hence, these data provide further evidence that protein phosphatase type-1 plays a major role in the control of glycogen synthesis by regulating the activities of glycogen synthase and phosphorylase. PMID- 8218372 TI - Depth-dependent change in membrane fluidity by phenolic compounds in bovine platelets and its relationship with their effects on aggregation and adenylate cyclase activity. AB - The effects of phenolic compounds on membrane fluidity of bovine blood platelets were investigated by studies on the fluorescence anisotropies of diphenylhexatriene (DPH) and its ionic derivatives to clarify the relationship of these effects with the inhibitory effects of the compounds on aggregation. Among the phenolic compounds tested, monohydric phenols (phenol and two monosubstituted derivatives) decreased the fluorescence anisotropy of DPH, which is thought to be located within the hydrophobic core of the membrane, in concentration ranges in which they inhibited platelet aggregation. On the other hand, they had little or no effects on the fluorescence anisotropies of the ionic derivatives of DPH, which are thought to be located in the interfacial region of the lipid bilayer. Consistent with their effects on the fluorescence anisotropy of DPH, these monohydric phenols increased the intracellular cAMP concentration. Thus, these monohydric phenols may inhibit platelet function by stimulation of adenylate cyclase mediated by perturbation of the central region of the membrane lipid bilayer. On the other hand, pyrocatechol and pyrogallol, which have two and three phenolic hydroxyl groups and have much larger electron donor activities than the monohydric phenols tested, inhibited platelet function by a different mechanism, because they did not cause increase in either membrane fluidity or the cAMP concentration of platelets. PMID- 8218373 TI - Mechanisms and genetics of photoreceptors desensitization in Drosophila flies. PMID- 8218374 TI - Stable expression of gp80 (TRPM-2, clusterin), a secretory protein implicated in programmed cell death, in transfected BHK-21 cells. AB - The gp80 (TRPM-2, clusterin) cDNA cloned into an eucaryotic expression vector, was transfected into BHK-21 cells and stably transformed cell clones were obtained. Analysis of the gp80 glycoprotein complex produced in these cells demonstrated that the complex was glycosylated, proteolytically processed and secreted in a way similar to the gp80 glycoprotein complex expressed from the endogenous gene in MDCK cells. The analysis of the viability of the cells, the morphology and the state of the DNA in the transfected cells was unchanged when compared with the untransformed cells, demonstrating that the expression of the protein failed to elicit any signs of apoptosis in this system. PMID- 8218375 TI - Structural and functional aspects of the interaction between growth hormone and its receptor. PMID- 8218376 TI - A pulse radiolytic study on the reaction of hydroxyl and superoxide radicals with yeast Cu(I)-thionein. AB - In a pulse radiolytic study employing aqueous intact yeast copper(I)-thionein at pH 7 it was shown that both superoxide and hydroxyl radicals efficiently react with this Cu(I)- and thiolate-rich protein. The reaction constant of hydroxyl radicals with Cu(I)-thionein was determined by competition kinetics and was 2.2 x 10(11) M-1 s-1 at a rate close to a diffusion-controlled limit. The reaction of Cu(I)-thionein with superoxide was also successful and proceeded at a rate of 7.5 x 10(6) M-1 s-1. According to chiroptical and luminescence emission measurements minor oxidation of the copper(I)-thiolate oligonuclear binding centres was observed, leading to the release of some Cu(II). It is important to realise the dual reactivity of this yeast Cu(I)-thiolate protein in controlling copper transport and storage as well as its distinct role in the scavenging of free radicals. PMID- 8218377 TI - Phosphorylation of human sperm protamines HP1 and HP2: identification of phosphorylation sites. AB - Human sperm is characterized by a high heterogeneity of its basic nuclear protein complement of pro-protamines, protamines and histones. This heterogeneity is increased by the persistence of phosphorylated protamines in mature spermatozoa. Alkaline phosphatase treatment of whole protein indicated that protamines HP1 and HP2 were phosphorylated to various degrees. Presence of non-phosphorylated and phosphorylated protamines HP1 and HP2 was further demonstrated by electrospray mass spectrometry. Phosphorylation sites of mono- and di-phosphorylated protamine HP1 were identified by automatic Edman degradation of the protein after phosphoserine derivatization to S-ethylcysteine. In both phosphorylated forms, Ser-10 was found phosphorylated; in the di-phosphorylated form, Ser-8 was identified as the second site of phosphorylation. In protamine HP2, the unique site of phosphorylation (Ser-14) was located after limited acid hydrolysis of enzymic peptides and thin-layer electrophoresis. PMID- 8218378 TI - Oxidative damage to lysozyme by the hydroxyl radical: comparative effects of scavengers. AB - The hydroxyl radical (OH.) is a highly-damaging reactive oxygen species, given its high reactivity and the consequent generation of secondary free radicals. This study was aimed at determining the qualitative and quantitative aspects of OH. scavenging by pentoxifylline (Ptx, a methylxanthine), uric acid and thymine on the OH.-induced alterations of a protein, lysozyme. Lysozyme was inactivated by OH. with a yield of 6.5 mol OH./mol lysozyme; moreover, SDS-PAGE showed a loss of native lysozyme (14.4 kDa), the presence of dimer and trimer aggregates and characteristic fragmentation. Tryptophan fluorescence was lost before aggregation became detectable in terms of bityrosine formation. Increasing concentrations of OH. scavengers gave increasing protection of lysozyme activity. Although all three compounds scavenge OH. with high rate constants, their effects were different: uric acid and Ptx prevented aggregation and preserved enzyme activity, whereas thymine preserved activity but did not prevent aggregation. These differences appear to be related to the formation of reducing secondary radicals, underlining the importance of this mechanism in the effects of scavengers. PMID- 8218379 TI - Kinetic mechanism of human erythrocyte acidic isoenzyme rho. AB - The kinetic mechanism has been determined for human glutathione S-transferase rho (rho), an isoenzyme related to the human pi (pi) isoenzyme. The kinetic mechanism was investigated by both non-linear regression studies and the analysis of primary and secondary plots, utilizing initial rate and product inhibition data. It was concluded that human isoenzyme rho obeys a random sequential Bi-Bi rapid equilibrium mechanism with the formation of an enzyme-substrate-product (enzyme CDNB-conjugate) dead-end complex. The values of KCDNB, KGSH and Kconjugate were 0.70 +/- 0.11, 0.12 +/- 0.02 and 0.016 +/- 0.004 mM, respectively. Comparison of the kinetic mechanism and kinetic parameters obtained for glutathione S transferase isoenzyme rho with other class pi isoenzymes showed similarities at the primary kinetic level. PMID- 8218380 TI - Cooperativity in the unfolding transitions of cysteine proteinases. Calorimetric study of the heat denaturation of chymopapain and papain. AB - Differential scanning calorimetry (DSC) was employed to study the thermal unfolding of chymopapain (EC 3.4.22.6) and papain (EC 3.4.22.2), two highly homologous cysteine proteinases from Carica papaya. Under all pH conditions used, both enzymes showed irreversible thermal denaturation. However, results from experiments performed at two different scanning rates suggest that interpretation of data in terms of equilibrium thermodynamics is not unreasonable. For papain, the ratio of calorimetric (delta Hcal) to van't Hoff (delta HvH) enthalpies approximated to 2.0. This value indicates that papain domains unfold almost independently, as it has been reported previously. In contrast, chymopapain displayed a more cooperative behavior with a delta Hcal to delta HvH ratio of 1.3 1.4. DSC curves were analyzed in terms of a mechanism that includes domain-domain interactions. The results showed a negligible interdomain free energy in the case of papain, but a significant value of approx. 1.0 kcal/mol (1 cal = 4.184 J) for chymopapain. These two proteins also differed in the unfolding heat-capacity change, delta Cp, which suggests that their native structures bury different amounts of nonpolar surface area. PMID- 8218381 TI - Chemical modification of bile acid: CoA ligase. AB - The effect of chemical modification of bile acid:CoA ligase on its enzymatic activity was examined. Reagents which modify tyrosine and carboxyl groups did not affect the activity of either the purified enzyme or the enzyme in its native microsomal environment. The modification of arginine residues with either diacetyl or phenylglyoxal resulted in a loss of activity for both the purified and microsomal forms of the enzyme. ATP was able to protect the enzyme from inactivation. Neither cholate nor CoA were able to alter the time-course of inactivation. The sulfhydryl reagent N-ethylmaleimide (MalNEt) produced a biphasic effect on both the purified and microsomal forms of the enzyme. At short reaction times ligase activity increased, but further reaction lead to nearly complete inactivation. With the purified enzyme, ATP increased the extent of activation by MalNEt and decreased the rate of inactivation. With microsomes, ATP did not affect the extent of activation by MalNEt, but did slow the rate of inactivation. For both the purified and microsomal forms cholate provided no protection. Treatment of both forms of the enzyme with the sulfhydryl reagent iodoacetic acid produced a similar biphasic activation/inactivation of the ligase. It was hypothesized that modification of a fast-reacting cysteine leads to activation while a slower-reacting cysteine leads to inactivation. This latter cysteine appeared to be in the ATP-binding site on the enzyme. PMID- 8218382 TI - Human Mu-class glutathione S-transferases present in liver, skeletal muscle and testicular tissue. AB - The major human Mu-class glutathione S-transferases (GST) have been purified to allow comparisons of their catalytic, physicochemical and immunochemical properties. GST isoenzymes, purified from hepatic, testicular and skeletal muscle tissue were found to comprise three distinct subunits (M1, M2 and M3) which may combine to form both homodimeric and heterodimeric proteins. Two distinct subunits, M1a and M1b, which represent allelic charge variants have been isolated but no polymorphic forms encoded at the GST M2 and M3 loci have been observed. Three GST isoenzymes (M1a-1a, M1a-1b and M1b-1b) have been purified from a single liver specimen. In addition, GST M1a-2, M1b-2, M2-2 and M2-3 have been isolated from muscle, whilst the M3-3 homodimer has been purified from human testis. The homodimeric enzymes GST M1a-1a, M1b-1b, M2-2 and M3-3 have pI values of 6.1, 5.5, 5.3 and 5.0, whilst SDS-PAGE indicated that M1a, M1b, M2 and M3 have molecular masses of 26.7, 26.6, 26.0 and 26.3 kDa, respectively. The M1, M2 and M3 subunits isolated from either liver, skeletal muscle or testis, are catalytically distinct. Both M1-type subunits (M1a and M1b) possess a high activity for trans-4 phenyl-3-buten-2-one, whereas, the skeletal muscle subunit M2 has a high activity towards 1,2-dichloro-4-nitrobenzene. By contrast, the testicular GST subunit M3 has no detectable activity towards either of these substrates. However, all three Mu-class subunits are active towards the compounds 4-hydroxynonenal and 4 hydroxydecinal, possible endogenous substrates which are produced by lipid peroxidation. The human Mu-class subunits can be distinguished immunochemically; antisera raised against the testicular GST M3-3 showed no reactivity towards either the M1 or M2 subunits. The M3 subunit has a blocked N-terminus but automated amino-acid sequencing of a CNBr-derived peptide allowed 14 residues of the M3 subunit to be identified. These data indicated that testicular GST M3-3 is likely to correspond to the brain/testis Mu-class GST cDNA described by Campbell et al. (Campbell E., Takahashi Y., Abramovitz M., Peretz M., & Listowsky I. (1990) J. Biol. Chem. 265, 9188-9193). PMID- 8218383 TI - Proton transfer in the catalytic mechanism of carbonic anhydrase. Effects of placing histidine residues at various positions in the active site of human isoenzyme II. AB - The maximal rate of CO2 hydration catalyzed by human carbonic anhydrase II (carbonate hydro-lyase, EC 4.2.1.1) is limited by proton transfer steps involving the acid-base function of His-64. To test whether or not the precise location of this proton transfer group is critical, histidine residues were placed in various positions in the active site of the enzyme. Thus, four double mutants were made, all with His-64 replaced by Ala-64, and with a histidine residue replacing Asn 62, Ala-65, Asn-67 or Thr-200. The results show that the mutants with His-62, His 67 and His-200, but not the mutant with His-65, yield significantly higher kcat values for CO2 hydration than the single mutant with Ala-64, indicating that His 62, His-67 and His-200 can contribute to proton transfer between the metal center and the reaction medium. However, the average proton transfer efficiency of these histidines is only about 5% of that of His-64 in the unmodified enzyme. PMID- 8218384 TI - Chemical modification of tissue inhibitor of metalloproteinases-1 and its inactivation by diethyl pyrocarbonate. AB - Tissue inhibitor of metalloproteinases-1 (TIMP-1) was treated with a range of chemical modification reagents in order to identify amino acid residues essential for inhibitory activity. Diethyl pyrocarbonate (DEPC) was found to be a potent inactivator at low reagent/TIMP molar concentrations. The extent of modification at 50% inactivation was determined as 1.5 sites/molecule. The DEPC-modified inhibitor did not form stable complexes with stromelysin, but was shown to retain native structure as judged by conformational stability to denaturation by guanidine hydrochloride. Peptide mapping experiments were used to find the sites of DEPC incorporation within the primary structure of TIMP and three residues were identified (His-95, His-144 and His-164). Mutant TIMPs in which histidine residues have been substituted or deleted retain inhibitory activity and were found to be equally as sensitive to DEPC inactivation as the wild-type. No new sites of DEPC modification in the mutant proteins were detected. The possible contribution made by His residues 95, 144 and 164 to the inhibitory activity of TIMP is discussed. PMID- 8218385 TI - Expression, purification and binding to the receptor of human insulin-like growth factor II. AB - Human insulin-like growth factor II (IGF-II) was expressed as a fused protein with 14 additive amino acids in Escherichia coli with a high yield by an expression system using T7 RNA polymerase. Purification of the expressed protein was simply performed using only differential ultrafiltrations, giving a homogeneous preparation upon polyacrylamide gel electrophoresis and high performance liquid chromatography. The expressed peptide was reacted with a monoclonal antibody raised against native IGF-II on a blotted membrane. Furthermore, the peptide was bound to IGF-II receptor in solubilized rat fetus membrane, though the affinity was slightly inferior to that of native IGF-II. In addition, fusion IGF-II immobilized on a gel matrix was useful for one-step purification of the IGF-II receptor with a high yield from solubilized rat fetus membranes. PMID- 8218386 TI - Characterization of a filtrable 3'-nucleotidase of Leishmania donovani. AB - A plasma membrane 3'-nucleotidase (3'-ribonucleotide phosphohydrolase, EC 3.1.3.6) having a apparent subunit molecular mass of 38 kDa but filtrable through a Centriprep-10 microconcentrator (Amicon) membrane was purified from Leishmania donovani promastigotes. The enzyme activity has an optimum at pH around 7.5. EDTA strongly inhibited the enzyme activity which was fully restored only by Co2+, from various metal ions added. Citrate ions, Zn2+ or dithiothreitol were also strongly inhibitory. The enzyme is apparently located on the inner side of the parasite plasma membrane. The substrate specificity and kinetics of the filtrable enzyme are similar to those of the non-filtrable outer-surface-membrane-bound 3' nucleotidase reported by Gbenle and Dwyer (Gbenle, G.O. and Dwyer, D.M. (1992) Biochem. J. 285, 41-46). Therefore, it is suggested that both enzymes are implicated in the supply of nucleosides to the parasite. PMID- 8218387 TI - Residues 287-301 of human ribonuclease inhibitor do not affect ribonuclease activity and inhibitor binding; a reply. AB - Residues 287-301 of human placental ribonuclease inhibitor have been reported to inhibit pancreatic ribonuclease A in a similar way as the entire inhibitor (Crevel-Thieffry, I., Cotterill, S. and Schuller, E. (1992) Biochim. Biophys. Acta 1122, 107-112). Using three different assays, we were unable to observe inhibition by the synthetic peptide. Moreover, the peptide did not compete with the entire inhibitor for binding to RNAase A. PMID- 8218388 TI - Dynamics of protoporphyrin IX in the heme pocket of horseradish peroxidase. AB - The local motion of protoporphyrin IX in the heme pocket of horseradish peroxidase has been studied using fluorescence methods. The temperature dependence of the anisotropy and lifetime of a protoporphyrin IX-apo-horseradish peroxidase complex, dissolved in a solution of 80% glycerol and 20% buffer (0.1 M phosphate, pH 7.4), was determined. Anisotropy data were analyzed in terms of the thermal coefficient of the frictional resistance to fluorophore movement. The resultant 'Y' plot was characterized by three distinct slopes. The slope corresponding to the lowest temperature regime agreed with the value obtained for fluorophores not complexed with protein. The slope corresponding to an intermediate temperature was lower indicating a larger resistance to porphyrin rotation. At higher temperatures this resistance to rotation diminished as evidenced by the increased slope. These results are contrasted with those obtained with the protoporphyrin IX-apomyoglobin complex. PMID- 8218389 TI - Physico-chemical characterization of a recombinant cytoplasmic form of lysine: N6 hydroxylase. AB - A recombinant cytoplasmic preparation of lysine: N6-hydroxylase, IucD398, with a deletion of 47 amino acids at the N-terminus, was purified to homogeneity. IucD398 is capable of N-hydroxylation of L-lysine upon supplementation with FAD and NADPH. The enzyme is stringently specific with L-lysine and (S)-2-aminoethyl L-cysteine serving as substrates. Protonophores, FCCP and CCCP, as well as cinnamylidene, have been found to serve as potent inhibitors of lysine: N6 hydroxylation by virtue of their ability to interfere in the reduction of the flavin cofactor. PMID- 8218390 TI - Inverse relationship of the dehydrogenase and ADP-ribosylation activities in sodium-nitroprusside-treated glyceraldehyde-3-phosphate dehydrogenase is coincidental. AB - Incubation of glyceraldehyde-3-phosphate dehydrogenase (GAPD) with sodium nitroprusside (SNP) decreased its activity in concentration- and time-dependent fashion in the presence of a thiol compound, with DTT being more effective than GSH. Both forward and backward reactions were effected. Coinciding with this, HgCl2-sensitive labelling of the protein by [32P]NAD+ also increased, indicating the stimulation of ADP-ribosylation. Treatment with SNP of GAPD samples from rabbit muscle, sheep brain and yeast inactivated the dehydrogenase activity of the three, but only the mammalian proteins showed ADP-ribosylation activity. The SNP-modified protein of rabbit muscle GAPD, freed from the reagent by Sephadex filtration showed a concentration-dependent restoration of the dehydrogenase activity on preincubation with DTT and GSH. Such thiol-treated preparations also gave increased ADP-ribosylation activity with DTT, and to a lesser extent with GSH. The SNP-modified protein was unable to catalyze this activity with the native yeast enzyme and native and heat-inactivated muscle enzyme. It was possible to generate the ADP-ribosylation activity in muscle GAPD, by an NO independent mechanism, on dialysis in Tris buffer under aerobic conditions, and on incubating with NADPH, but not NADH, in muscle and brain, but not yeast, enzymes. The results suggest that the inverse relationship of the dehydrogenase and ADP-ribosylation activities is coincidental but not correlated. PMID- 8218391 TI - A kinetic study of an unstable enzyme measured through coupling reactions. Application to the self-inactivation of detergent-solubilized Ca(2+)-ATPase from sarcoplasmic reticulum. AB - A methodology for the kinetic study of the self-inactivation of an unstable enzyme has been developed by using the transient-phase approach when the enzymatic activity is measured through a coupled enzyme system. An experimental design has been developed and applied to the inactivation of the Ca(2+)-ATPase from sarcoplasmic reticulum solubilized in the monomeric state. The catalytic activity of the ATP hydrolysis is determined in the presence of pyruvate kinase and lactate dehydrogenase as auxiliary enzymes, and the oxidation of the last substrate, NADH, is continuously monitored. The experimental results show that both substrates, ATP and calcium, protect against enzyme inactivation. This enzyme, the monomeric ATPase, fulfills the catalytic cycle of the native ATPase, and free enzyme and first-calcium bound enzyme are proposed as the intermediates which are being inactivated. PMID- 8218392 TI - The caldesmon content of vertebrate smooth muscle. AB - Caldesmon and tropomyosin can be selectively and quantitatively extracted from vascular and visceral smooth muscle following heat treatment; all other smooth muscle proteins are precipitated by this procedure. Estimates of the caldesmon/tropomyosin molar ratio in heat-extracts determined by SDS-PAGE densitometry are 1 caldesmon:5.1-5.3 tropomyosin for rabbit and sheep aorta, and 1 caldesmon:5.9 tropomyosin for rabbit stomach and chicken gizzard. If the assumption is made that tropomyosin serves as a true reference of thin-filament content in intact muscle, it follows that the relative caldesmon contents in the above tissues are similar to each other. Caldesmon in heat extracts was identified by Western blotting, by its anomalous migration on several different SDS-PAGE systems and by its position on two-dimensional PAGE. Values of caldesmon contents in unfractionated total tissue homogenates were found to be similar to those cited above. Smooth muscles contain different thin-filament classes and only one type appears to possess caldesmon. By comparing values for the molar composition of caldesmon-specific filaments (1 caldesmon:2 tropomyosin:14 actin) with the values above determined for intact tissue, we conclude that the caldesmon filaments account for approx. 35-45% of the total thin-filament pool in arterial smooth muscle and slightly less in visceral muscles. PMID- 8218393 TI - Chemical modification of the Ca(2+)-ATPase of rabbit skeletal muscle sarcoplasmic reticulum: identification of sites labeled with aryl isothiocyanates and thiol directed conformational probes. AB - The Ca(2+)-ATPase protein of rabbit skeletal muscle sarcoplasmic reticulum is a single polypeptide chain of 1001 amino-acid residues. Among these residues are 24 Cys, 9 of which have previously been shown to be accessible to one or more thiol specific reagents. Many studies on the structure and function of this Ca(2+) ATPase have made use of sulfhydryl-directed, conformationally-sensitive probes, but the labeling sites for these probes have been directly identified in only a few cases, causing uncertainty in the interpretation of results. In the present work, we have investigated the Ca(2+)-ATPase labeling sites for three thiol directed spectroscopic probes: fluorescein 5'-maleimide (Fmal), 4 dimethylaminophenyl-azo phenyl-4'-maleimide (DABmal), and 4 dimethylaminophenylazophenyl-4'-iodoacetamide (DABIA). Labeled Ca(2+)-ATPase was digested exhaustively with trypsin, and labeled peptides were purified and sequenced in order to identify the labeled Cys residues. Our results do not support the widely held assumptions that Cys-344 and Cys-364 are the most reactive residues with maleimide-based reagents, while Cys-670 and Cys-674 react most rapidly with iodoacetamide derivatives. We found instead that Fmal reacted most rapidly with Cys-471, followed by Cys-364, and more slowly with Cys-498, 525, -614 and -636. DABmal reacted most rapidly with Cys-364, followed by Cys 614, and more slowly with Cys-471, -498, -636 and -670. Cys-344 was not labeled by either Fmal or DABmal. DABIA reacted with the same six Cys residues, including Cys-670, as were labeled with DABmal, but in much lower yield. There was no evidence for labeling of Cys-674 with DABIA. The high reactivity of Fmal, but not the more hydrophobic DABmal, with Cys-471 is of interest because of previous studies suggesting that the accessibility of Cys-471 is influenced by ATP and that fluorescein derivatives bind to a hydrophobic pocket in the ATP binding site. Another derivative, fluorescein-5'-isothiocyanate (FITC), is thought to label the catalytic site of the Ca(2+)-ATPase and has been widely used as a conformational probe in structure-function studies on this and related proteins. We reinvestigated the chemical modification of the Ca(2+)-ATPase by FITC and 4 dimethyl-aminophenyl-4'-isothiocyanate (DABITC). Incorporation of stoichiometric amounts of FITC resulted in a nearly complete loss of ATPase activity. Labeling and inactivation of the Ca(2+)-ATPase by FITC did not occur in the presence of ATP. DABITC was less reactive than FITC, and did not inactivate the Ca(2+)-ATPase to any significant extent.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8218394 TI - A tyrosine residue is involved in the allosteric binding of tryptophan to yeast chorismate mutase. AB - Comparative 1H-NMR studies have been carried out on wild-type chorismate mutase, which is activated by tryptophan and inhibited by tyrosine and phenylalanine, and mutant yeast chorismate mutase, which has a single point mutation (T226I) and is not allosterically regulated but 'locked' in the activated state. Double quantum filtered COSY spectra show cross-peaks which have been assigned to a tyrosine that are absent in the mutant enzyme and in the wild-type enzyme plus tryptophan when compared with the wild-type enzyme alone. These observations indicate the involvement of a tyrosine at or near the allosteric binding site. The involvement of tyrosine in tryptophan binding was tested by modification of tyrosine in yeast chorismate mutase by nitration with tetranitromethane. All forms of the enzyme exhibited an approx. 50% reduction in specific activity, but it was found that preincubation of the wild-type with the allosteric activator, tryptophan, lead to partial protection against loss in specific activity. Only one tyrosine residue was nitrated in the wild-type enzyme and this tyrosine was identified by tryptic digestion and sequencing, and found to be very close to the site of the single point mutation in the mutant enzyme. It is proposed that Tyr-234 is located at or near the allosteric activation site. PMID- 8218396 TI - EPR studies on the photoproducts of manganese(II) protoporphyrin-IX substituted myoglobin nitrosyl complexes trapped at low temperature: effects of site-specific chemical modification of the distal histidine on ligand-binding structures. AB - Manganese(II) protoporphyrin-IX substituted myoglobin with site-specifically cyanated or N-tetrazolated distal histidine (His) was prepared and low temperature photolysis of nitric oxide (NO) from their nitrosyl complexes was examined by electron paramagnetic resonance (EPR) spectroscopy in order to elucidate the steric crowding of the distal heme moiety. The photoproduct of NO complex of the tetrazolated Mn(II)Mb (tetrazole-Mn(II)Mb) exhibited widespread absorption in the magnetic field from zero to 0.4 T due to a spin-coupled interaction between the high-spin Mn(II) center (S = 5/2) and the photodissociated NO (S = 1/2) trapped adjacent to the metal center. This indicates that the NO complex of tetrazole-Mn(II)Mb has sterically restricted distal heme pocket. On the other hand, the photoproduct of NO complex of cyanated Mn(II)Mb (BrCN-Mn(II)Mb) exhibited only the broad g = 6 absorption due to the magnetic dipole-dipole interaction between the photodissociated NO and the high spin Mn(II) center. A drastic conformational change in the heme-ligand moiety, in which the distal histidine side chain is pushed toward the outside of the heme pocket, leaving an open space in the distal heme pocket, can be suggested. PMID- 8218395 TI - The role of acidic amino-acid residues in catalytic and adsorptive sites of Bacillus cereus sphingomyelinase. AB - By the modification of acidic amino-acid residues with Woodward's reagent K (N ethyl-5-phenylisoxazolium-3'-sulfonate), the activity of sphingomyelinase of Bacillus cereus was decreased by 80-90%. Also, the reduction of Cys residues in the sphingomyelinase molecule by dithiothreitol caused a drastic decrease in enzymatic activity, whereas the sphingomyelinase activity was not affected by treatment with p-chloromercuribenzenesulfonic acid. Actually, no inactivation of sphingomyelinase activity was observed after selective modification of basic amino-acid residues such as Lys, His and Arg, and of the uncharged amino-acid residues Ser and Thr. The treatment of the sphingomyelinase molecule with Woodward's reagent K or dithiothreitol also brought about the inhibition of the specific adsorption of sphingomyelinase toward intact erythrocyte membranes. However, the extent of inhibition in the enzyme adsorption, 20-50%, was less than that observed in the sphingomyelinase activity. These results suggest that acidic amino-acid residues, such as Asp and Glu, in the sphingomyelinase molecule are involved in the catalytic sites and the adsorptive sites. Apparently, the disruption of disulfide linkage in the sphingomyelinase molecule by dithiothreitol destabilized its structure, resulting in a drastic decrease in sphingomyelin-hydrolyzing activity and specific adsorption of sphingomyelinase towards erythrocyte membranes. PMID- 8218397 TI - Bidirectional transcription from actin promoters in Dictyostelium. AB - Numerous transformation vectors for Dictyostelium discoideum have been constructed by fusing actin 6 and 15 promoters to selectable markers such as G418 and hygromycin. Strand specific probing of RNAs from transformed cells demonstrates that cells containing these vectors accumulate transcripts representing both strands of the vector. The evidence is consistent with bidirectional transcription initiating in the truncated actin promoter fragments. A larger fragment of the actin 15 promoter largely eliminates this problem. PMID- 8218398 TI - The primary structure of two proteins from the large ribosomal subunit of rice. AB - We isolated two rice cDNAs which encode an open reading frame of 389 amino acids. Their deduced amino acid sequence corresponded to the ribosomal protein (r protein). A comparison of amino acid sequence shows that the deduced amino acid sequence of one cDNA is homologous to Arabidopsis, yeast and the rat r-protein L3. Another encoded products with a high degree of homology to the rat r-protein L7A and yeast r-protein L4. PMID- 8218399 TI - The primary structure of two proteins from the small ribosomal subunit of rice. AB - We isolated two rice cDNAs which encode an open reading frame of 117 amino acids or 82 amino acids. Their deduced amino acid sequence correspond to the ribosomal proteins (r-protein). A comparison of the amino acid sequence shows that the deduced amino acid sequence of one cDNA is homologous to the rat r-protein S20 and Xenopus r-protein S22. Another encoded products with a high degree of homology to the rat r-protein S21 and the yeast r-protein YS25. PMID- 8218400 TI - Nucleotide sequence of the Lactococcus lactis NCDO 763 (ML3) rpoD gene. AB - The complete nucleotide sequence of rpoD gene from Lactococcus lactis has been determined. The nucleotide data have indicated the presence of an open reading frame of 1020 base pairs encoding a polypeptide which shares the framework structure for principal sigma factors of eubacteria strains. PMID- 8218401 TI - Molecular cloning and sequence analysis of U3 snoRNA-associated mouse fibrillarin. AB - We have isolated and determined the sequence of a 1.1-kb cDNA from a murine WEHI 3 macrophage library which encodes the highly conserved, nucleolar protein, fibrillarin. The murine fibrillarin protein sequence displays 94.2% identity with human fibrillarin, 82.9% identity with amphibian fibrillarin and 74.0% identity with the yeast fibrillarin homolog, NOP1. Immunoprecipitation showed that anti fibrillarin autoantibodies from human scleroderma sera and the monoclonal autoantibody 72B9 recognize the approx. 34-36 kDa in vitro transcribed and translated protein. Mouse fibrillarin contains a N-terminal glycine- and arginine rich (GAR) domain which although conserved among the fibrillarins is not as strongly conserved as several regions in the carboxy tail of the protein. Specific amino acid residues in yeast NOP1 thought to be associated with the synthesis and maturation of ribosomes show strong conservation between the mouse, human, amphibian and yeast protein sequences. PMID- 8218402 TI - cDNA sequence for mouse caltractin. AB - Caltractin, a contractile Ca(2+)-binding protein, has not been found in any species other than algae. We now report the first isolation and sequencing of cDNA encoding mouse caltractin from a testis cDNA library by immunoscreening. Mouse caltractin has a molecular mass of 20 kDa, which is the same as that from algae. PMID- 8218403 TI - A highly conserved repetitive sequence from Physarum polycephalum contains nucleotide arrangements similar to replicator sequences. AB - An interspersed repetitive sequence from Physarum polycephalum has been cloned and analysed. The 394 bp sequence is highly conserved and contains several homopolymeric (dA)-(dT) tracts capable of forming bent DNA structures and a 10/11 match to the yeast-ARS-consensus sequence. The repetition frequency of the described sequence is about 3000 to 7000, a number that would fit with the distribution of replicator segments in Physarum. PMID- 8218404 TI - Nucleotide and deduced amino acid sequence of human ribosomal protein L18. AB - Ribosomal protein L18 mRNA is overexpressed in human colorectal cancer compared to normal colon tissue. We report the nucleotide sequence of human L18 cDNA derived from a normal colon source. There were no mutational changes in segments of L18 cDNA derived from two tumor sources. The L18 cDNA was 690 base pairs long and predicts a single open reading frame of 564 nucleotides, encoding 188 amino acids with a M(r) = 21,621, it is homologous to rat L18 and Xenopus laevis L14. PMID- 8218405 TI - Clusters of 5S rRNAs in the intergenic region of ubiquitin genes in Tetrahymena pyriformis. AB - Here, we report the molecular analysis of two independent 5S rRNA clusters found in the intergenic region of two ubiquitin genomic clones isolated from Tetrahymena pyriformis. Each cluster contains two 120-bp-long coding regions organized in tandem with 142/145-bp-long spacers. PMID- 8218406 TI - The human and bovine 14-3-3 eta protein mRNAs are highly conserved in both their translated and untranslated regions. AB - 14-3-3 proteins form a highly conserved protein family whose members have been shown to activate tyrosine and tryptophan hydroxylases, inhibit protein kinase C and possess phospholipase A2 activity in vitro. We have isolated and analyzed a 14-3-3 protein cDNA clone (H14-3-3) from a human fetal brain cDNA library and found it to possess a high level of sequence identity with the bovine 14-3-3 eta protein cDNA in both the translated and untranslated regions, suggesting the presence of cis-regulatory elements in the untranslated regions of these mRNAs. The proteins encoded by these two cDNAs are 98.4% identical. Two different sized RNA species, approx. 1.9 and 3.5 kb in size that are expressed in a variety of tissues hybridize with this cDNA. However, only the 1.9 kb RNA is detected in the fetal brain. Northern blot analysis of poly(A)+ RNA isolated from eight different human tissues shows that 14-3-3 protein mRNAs are expressed in many tissues in the body. In agreement with previous reports, the highest abundance of RNA hybridizing with this cDNA is seen in the brain. PMID- 8218407 TI - Ubiquitous factors that interact simultaneously with two distinct cis-elements on the rat aldolase B gene promoter. AB - The proximal promoter region (nucleotide -202 to -1) of the rat aldolase B gene confers liver-specific transcription, and contains three indispensable protein binding sites (site A, site B and site C). Site A binds HNF-1 and HNF-3, and site B binds NF-Y and a CCAAT-binding factor AlF-B (Tsutsumi et al. (1989) Mol. Cell. Biol. 9, 4923-4931; Raymondjean et al. (1991) Nucleic Acids Res. 19, 6145-6153), trans-acting factors that interact with site C, however, have not been well characterized. In this study, we identified specific factors that bind site C by two-dimensional gel electrophoretic analyses. The factors interacted with two distinct cis-elements; site C and site B. This observation, together with the fact that site C contains a C/EBP binding motif, implied that the site C-binding factors are members of C/EBP family. However, analyses of their binding characteristics, their relative molecular masses, and their distribution in different cell types showed that the site C binding factors are different from known members of C/EBP family. PMID- 8218408 TI - The complete cDNA coding sequence for the mouse CDEI binding protein. AB - This work describes the cDNA sequence of the mouse CDEI binding protein (CDEBP), comprising the complete coding sequence. The cDNA encodes a protein of 695 amino acid residues. The derived amino acid sequence displays a sequence identity to human amyloid precursor-like protein (APLP) of > 92%. PMID- 8218409 TI - Cloning and sequence analysis of a murine cDNA encoding glutamate decarboxylase (GAD65). AB - We report the cloning and cDNA sequence of murine GAD65. Murine GAD65 is comprised of 585 amino acids and shares a high degree of homology with human and rat GAD65, with most divergences occurring near their amino-termini. The murine GAD65 sequence will allow evaluation of the role of this gene in murine neurogenetic and autoimmune diseases. PMID- 8218410 TI - Cloning and characterization of a glutamate transporter cDNA from human cerebellum. AB - The glutamate/aspartate transporters are essential for the elimination and recycling of synaptic glutamate released from nerve endings during neurotransmission. Evidence suggests that these processes are altered in ischemia and neuronal degenerations linked to excitotoxicity. We screened a cDNA library constructed from human cerebellar mRNA, and isolated a cDNA that shows an 88.5% and a 98.7% sequence similarity at the nucleotide and amino acid level, respectively, with a rat brain specific Na(+)-dependent glutamate/aspartate transporter. The human cDNA is expressed in brain and it may prove useful in the study of human neurodegenerations linked to glutamate dysfunction. PMID- 8218411 TI - The cloning of eggplant seedling cDNAs encoding proteins from a novel cytochrome P-450 family (CYP76). AB - Using a CYP75 cDNA as a probe, we have cloned and sequenced two closely related cDNAs from eggplant seedlings, which encode typical cytochrome P-450 (P450) proteins. A database search revealed that the predicted proteins share less than 40% amino acid homology with other P450 proteins, which suggests that they form a novel P450 gene family (CYP76). PMID- 8218412 TI - Cloning of cDNA for the beta-subunit of rabbit translation initiation factor-2 using PCR. AB - RNA was isolated from rabbit liver and used to direct the synthesis of total cDNA. Rabbit eIF-2 beta transcripts were then specifically amplified by PCR and sequenced. RACE (rapid amplification of cDNA ends) was used to obtain 3' and 5' sequences. Comparison of the deduced amino acid sequence with that of human eIF-2 beta reveals a very high degree of sequence identity. PMID- 8218414 TI - Purification and partial characterization of single-chain ribosome-inactivating proteins from the seeds of Phytolacca dioica L. AB - Three ribosome-inactivating proteins (RIPs) similar to those already known (Stirpe et al. (1992) Bio/Technology 10, 405-412) were purified from the seeds of Phytolacca dioica. These proteins, called Phytolacca dioica RIPs (PD-S1, PD-S2 and PD-S3 RIPs), are glycoproteins, with M(r) approx. 30,000, inhibit protein synthesis by a rabbit reticulocyte lysate and phenylalanine polymerization by isolated ribosomes, and depurinate rat liver rRNA in an apparently identical manner as the A-chain of ricin and other RIPs (Endo et al. (1987) J. Biol. Chem. 262, 5908-5912). Part of the purified rat liver ribosomes appeared resistant to the action of PD-S RIPs. The most abundant protein, PD-S2 RIP, gave a weak or nil cross-reaction with sera against various other RIPs, including a pokeweed antiviral protein from the roots of Phytolacca americana. PD-S2 RIP was linked to a monoclonal antibody (Ber-H2) against the CD30 human lymphocyte antigen and the resulting immunotoxin was selectively toxic to the CD30 + Hodgkin's lymphoma derived L540 cell line. PMID- 8218413 TI - Distribution and properties of major ribosome-inactivating proteins (28 S rRNA N glycosidases) of the plant Saponaria officinalis L. (Caryophyllaceae). AB - We have studied the distribution of the protein synthesis inhibitory activity in the tissues of Saponaria officinalis L. (Caryophyllaceae). Seven major saporins, ribosome-inactivating proteins, were purified to apparent homogeneity from leaves, roots and seeds using a new procedure of RIPs isolation including ion exchange and hydrophobic chromatography. They all catalysed the depurination of rat liver ribosomes, which generate the Endo's diagnostic rRNA fragment upon treatment with acid aniline, thus indicating that A4324 from the 28S rRNA has been released (Endo et al. (1987) J. Biol. Chem. 262, 5908-5912). The molecular mass of saporins by SDS-PAGE ranged between 30.2 and 31.6 kDa and by gel filtration between 27.5 and 30.1 kDa. Amino acid composition and amino-terminal amino acid sequence indicate that all saporins may be considered isoforms. Only two saporins present in roots were glycosylated (SO-R1 and SO-R3). All saporins are very active on cell-free translation systems derived from rabbit reticulocyte lysates, rat liver, Triticum aestivum L., Cucumis sativus L. and Vicia sativa L. However, they are poor inhibitors of an Escherichia coli translation system. They inhibit protein synthesis in HeLa, BeWo and NB 100 cells, HeLa cells being the most resistant. The enzymatic activity of at least one saporin isoform was dependent on magnesium concentration in the standard rat liver cell-free system. PMID- 8218415 TI - DNA hypomethylation and differentiation in Friend leukemia cell variants. AB - The occurrence, upon differentiation, of a transient DNA hypomethylation has been observed in Friend erythroleukemia cells. Treatment with hexamethylenebisacetamide (HMBA) induces within 24 h a 20% hypomethylation of newly synthesized DNA, that is followed by re-methylation before completion of the differentiative process, as measured by the appearance of benzidine-positive cells. We examined a series of mutant clones which continue to grow in the presence of an inducer. Methylcytosine content of DNA was measured by HPLC, after cell labeling with [3H]uridine. We found that one of these continuously growing clones, which was still capable of hemoglobin synthesis, showed the same degree of hypomethylation as the parental one. The re-methylation process did not occur, however, unless erythroid differentiation was reverted by the removal of the inducer. In another clone which had lost the capacity to synthesize hemoglobin, no DNA hypomethylation was detectable. These experiments show that DNA hypomethylation is an early event strictly related to cell differentiation but not to cell growth arrest. PMID- 8218416 TI - Analysis of regulatory elements flanking metallothionein genes in Cd-tolerant fish (pike and stone loach). AB - From genomic libraries constructed for both pike and stone loach, clones were isolated containing the metallothionein genes from these two species of cadmium tolerant fish. A single copy metallothionein gene was identified in each species by Southern blot analysis. Sequencing revealed that each gene consisted of three exons followed by polyadenylation signals at the 3' end. In the 5' flanking region, putative metal responsive elements were identified both close to the transcription start site and clustered distally approx. 500 bp upstream. Neither gene locus showed any homology with the glucocorticoid or interferon responsive elements that have been identified in mammalian species. The significance of the absence of such responsive elements and their replacement by additional metal responsive elements in the same location of the 5'-flanking region of the MT genes is discussed in relation to the organisation of the MT gene loci in (the Cd sensitive) rainbow trout and higher mammalian species. PMID- 8218417 TI - Molecular cloning of cDNAs for two Xenopus proteasome subunits and their expression in adult tissues. AB - Proteasome, a large protein complex with ATP-dependent protease activities, is composed of non-identical but closely related multi-subunits. Using cDNAs for rat proteasome subunits as probes, we obtained three cDNA clones for two Xenopus proteasome subunits from ovary cDNA library. The primary structures of the three cDNAs showed high homology to the corresponding proteasome subunits of other mammalian species (above 90%) and also considerable homology to those of Drosophila and yeast. These results indicate that the sequences of proteasome subunits are well conserved during evolution. Northern blot hybridization revealed that RNAs for the newly isolated subunits (XC8 and XC9) and the previously isolated subunit (XC3) occur at very high levels in testis and ovary, at moderately high levels in lung, skin kidney and spleen, and at low levels in liver, stomach and muscle. It was also shown that relative amounts of the mRNAs for the three subunits are similar in all the adult tissues examined. From these results, we concluded that the expression of the genes for the three subunits (XC3 XC8 and XC9-1) takes place in a roughly coordinated manner in different adult tissues. PMID- 8218418 TI - Initiator sequences direct downstream promoter binding by human transcription factor IID. AB - Whereas the human transcription factor IID generally interacts with only the TATA box element on most class II gene promoters, on certain promoters (e.g., the adenovirus 2 major late promoter) TFIID protects DNA sequences up to +35 base pairs downstream of the start site of transcription from DNase I cleavage. In this study, we show that Ad2 MLP sequences from -3 to +5 were sufficient to direct downstream promoter binding by TFIID when introduced into the human hsp70 gene promoter. These sequences correspond to the initiator transcription control element. Initiator mutations resulting in a loss of downstream binding demonstrated a diminished transcription efficiency in vitro. Likewise, initiator dependent transcription stimulation required TFIID fractions capable of downstream promoter binding. Given the recent findings that immunopurified, human TFIID exhibited downstream promoter binding on the Ad2 MLP (Zhou, Q., Lieberman, P.M., Boyer, T.G. and Berk, A.J. (1992) Genes Dev. 6, 1964-1974), our data suggest that human TFIID can recognize the initiator element and that this interaction is required for maximally efficient transcription initiation. PMID- 8218419 TI - Molecular cloning and bacterial expression of cDNA for rat calpain II 80 kDa subunit. AB - The complete cDNA of 3.2 kb for rat calpain II large subunit has been constructed from library- and polymerase chain reaction-derived fragments, and sequenced. The cDNA encodes a protein of 700 amino acids having 93% sequence identity with human calpain II, and 61% identity with human calpain I. The gene possesses 21 exons, of which exons 3-21 have been mapped over 33 kb of the rat genome. A new phagemid expression vector was created from pT7-7 by insertion of the f1 origin and mutation of an NdeI to an NcoI site. Rat calpain II cDNA ligated into this vector expressed in Escherichia coli an 80 kDa protein identical in size to highly purified rat calpain II; this protein was specifically recognized on immunoblots by an affinity-purified anti-rat calpain II antibody. This is the second mammalian calpain II large subunit to be fully sequenced, and the first to be artificially expressed. PMID- 8218420 TI - Molecular cloning of two novel protein kinase genes from Arabidopsis thaliana. AB - We have isolated two novel protein kinase genes, MHK and NAK, from the plant Arabidopsis thaliana by using low stringency hybridization with the catalytic domain of a putative plant receptor protein kinase. Sequence analysis of the cDNAs reveals that MHK is a member of the cdc2+ family of protein kinases and is particularly similar to the mak gene of rats; mak encodes a protein kinase that may play a role in spermatogenesis. NAK encodes a candidate protein kinase that is similar to the oncogenes met and abl. The homology that these two Arabidopsis genes share with other protein kinases suggests that they may play a role in the regulation of plant growth and development. PMID- 8218421 TI - An AP-1 binding site in the upstream region of Deb-A is part of a developmentally regulated negative element. AB - The Deb-A gene from Drosophila melanogaster encodes a small membrane-associated protein, regulated during development, with peak abundance at 12-15 h of embryogenesis. The cis-acting regulatory elements that control expression of Deb A during embryogenesis were localized using a somatic transformation assay. The Adh gene of D. melanogaster was used as a 'reporter' gene. The promoterless ADH coding sequence was fused to the 5'-upstream control region of Deb-A. Deletions were introduced into the 5'-region using various restriction sites and Bal31 deletion mutagenesis. A negative regulatory element, or silencer, was localized to a segment 47 base pairs long, between -395 and -442. It is responsible for 80% of the repression of gene expression during late development and reduces levels of Deb-A RNA nearly 5-fold. This negative element is temporally functional. It becomes active after 15 h of embryogenesis and it has no effect on gene expression prior to that. Within this negative element of 47 base pairs, two footprint regions were protected from DNase I digestion by embryonic nuclear extracts: one region contains an AP-1 binding site, but the other footprint is due to unknown element(s). High molecular weight DNA-protein complexes on an oligonucleotide probe spanning the AP-1 binding site were identified in gel retardation assays using partially purified bacterially expressed Djun protein or nuclear extracts from Drosophila embryos. These data suggest that the AP-1 site may be partly responsible for decreasing Deb-A expression during the late embryonic developmental stages of D. melanogaster. PMID- 8218422 TI - Differential electron capture mass spectral response of pentafluorobenzoyl derivatives of platelet activating factor alkyl chain homologs. AB - The electron capture mass spectrometric response of pentafluorobenzoyl ester derivatives of platelet-activating factor alkyl chain homologs has been found to be inversely proportional to their alkyl chain length. This phenomenon was observed when either the gas chromatograph or direct insertion probe was utilized for sample introduction. A similar differential response was also obtained for a series of fatty alcohols, analyzed as pentafluorobenzoyl esters. These studies demonstrate that multiple standard curves must be prepared for analysis of platelet-activating factor and related lipids in order to obtain accurate quantification. PMID- 8218423 TI - Femtogram on-column detection of nicotine by isotope dilution gas chromatography/negative ion detection mass spectrometry. AB - A gas chromatographic method, utilizing detection by negative chemical ionization (NCI) mass spectrometry, is presented for the detection of nicotine. The method incorporates derivatization with heptafluorobutyric anhydride/pyridine to yield the ring-opened addition product, 1-[4-(3'-pyridyl)-4-heptafluorobutyryloxybutyl] 1- methylheptafluorobutanamide. The resulting heptafluorobutanamide is both relatively stable and an excellent electron scavenger. This methodology provides for the detection of nicotine at femtogram on-column levels, the measurement of nicotine over three orders of magnitude, and the minimization of contamination due to environmental nicotine. PMID- 8218424 TI - Confirmation of danofloxacin residues in chicken and cattle liver by microbore high-performance liquid chromatography electrospray ionization tandem mass spectrometry. AB - A specific assay is described for the confirmatory identification of danofloxacin residues in edible tissues of cattle and chicken. The assay utilizes on-line microbore high-performance liquid chromatography and pneumatically assisted electrospray tandem mass spectrometry (MS/MS). Collision-induced dissociation of the danofloxacin protonated molecule results in two significant daughter ions. Monitoring both ions provides the specificity required for this confirmatory assay. Optimum electrospray and MS/MS operating conditions permitted the specific monitoring of danofloxacin and the confirmation of its residues in chicken and cattle liver extracts down to 50 ppb. The analysis of control liver or the commercially available antibacterial quinolones enrofloxacin and its metabolite ciprofloxacin gave no response under the assay conditions. The ratios of the two daughter ions were similar for danofloxacin standard solutions, fortified tissues and incurred tissues. PMID- 8218425 TI - Determination of the isotope enrichment of one or a mixture of two stable labelled tracers of the same compound using the complete isotopomer distribution of an ion fragment; theory and application to in vivo human tracer studies. AB - Calculations of flux rates for stable isotope tracer studies are based upon enrichment values of an infused tracer. We propose the determination of enrichment values by gas chromatography/mass spectrometry, which is based on tracer mole fraction and mass spectrometer signals, normalized over the total signal of an ion fragment isotopomer distribution. The method accounts for overlap of the signals of one or two tracers and the tracee, high tracer mole fraction and incomplete labelling of the (infused) tracer. For the single and multiple tracer case a linear relationship between tracer mole fraction (from zero to one) and all normalized mass spectrometer signals is derived. This linearity over the entire range is demonstrated with a single (1-13C)glucose tracer and for mixtures of (1-13C)- and (3,3-2H2)tyrosine tracers. The linearity allows determination of the tracer mole fraction for two tracers, using multiple linear regression. The corresponding calibration can rely on measurements of the pure tracer and tracee compound, without weighing or check for chemical purity. This is compared with a calibration based on tracer/tracee mixtures. Estimates for the tracer mole fraction are slightly better if based on a calibration, using standard mixtures. In all cases the tracer mole fraction can be determined with high precision (coefficient of variation smaller than 5%) and high accuracy. For tyrosine it is demonstrated that the measurement of seven channels rather than three, for the main isotopomers, does not reduce the precision in the prediction of the tracer mole fraction. Equations are also derived to use the tracer mole fraction to estimate the endogenous production of the tracee under study conditions, assuming a steady state of the host metabolism. PMID- 8218426 TI - Post-psychotic depression in schizophrenia. AB - Post-psychotic depression (PPD) is defined as the development of depression during the phase of remission of schizophrenia. Two groups of DSM-III-R schizophrenics, one with PPD and the other without PPD (30 subjects in each group) were compared. Significantly more patients in PPD group belonged to nuclear families, had longer duration of psychotic phase of the illness, were hospitalised more frequently and had more sadness and anxiety-somatisation during florid illness phase. The PPD group also had more past history of depression. Although PPD patients had better premorbid personal-social adjustment in comparison with non-PPD group, they perceived themselves to be lacking in social support and had experienced more stressful life events. For patients in the PPD group, stepwise multiple regression analysis revealed age of onset, sadness during florid psychotic state, premorbid adjustment, social support and life events as significant determinants of severity of depression in the post psychotic phase. PMID- 8218427 TI - The closure of a mental hospital in Sweden. 5 years of transition to district based long-term care. AB - A political decision to decentralize psychiatric care in a county of Sweden was made in October 1984. This will lead to the closure of the county's only large psychiatric hospital. Short-term psychiatric care will be provided by three smaller hospitals in the county, while long-term care in hospital will cease completely and be replaced by district-based psychiatric services. All patients (n = 199) in the large hospital's long-term unit were studied over 5 years of the transition period. The results showed that 42% of patients were discharged during the period, mainly to other institutions. Only 8 patients were provided with alternative types of care, such as group homes. Sixty-eight per cent of all patients died, most of them before being discharged (80% of the organically demented patients and 51% of the others). The mortality rate for patients with severely impaired activities of daily living (ADL functioning) was 92% for those who were also organically demented and 84% for the others. The patients who survived the 5-year period were mainly (80%) nondemented patients with relatively well-preserved ADL functioning, but with behavioural disturbances. PMID- 8218428 TI - The psychopathology, neuropsychology, and neurobiology of associative and working memory in schizophrenia. AB - A large number of psycholinguistic findings on how human beings store lexical information suggest the existence of associative memory, which may be characterized by a large capacity and a long duration. Its anatomical basis supposedly is, at least in part, the frontal lobes, and some of its functional characteristics have been tentatively linked to dopamine release. Working memory has a limited capacity, lasts only for seconds and is relevant for goal-directed behavior. Its anatomical basis in the frontal cortex is established and strong evidence suggests the involvement of dopaminergic pathways. Experimental evidence using several lexical decision tasks and a delayed response task is provided to demonstrate that some characteristic features of schizophrenic thinking--in particular the rapid shift of associations, the indirect relationship of associations, the overly abstract or overly concrete use of concepts, the lack of context-sensitivity and of general integrative function and intellectual capacity -can be explained in terms of an activation or disinhibition of associative memory, and of a dysfunctional working memory. The findings serve as an example of schizophrenia research in a cognitive neuroscience framework. PMID- 8218429 TI - Chronological changes of MRI findings on striatal damage after acute cyanide intoxication: pathogenesis of the damage and its selectivity, and prevention for neurological sequelae: a case report. AB - A 31-year-old male technician in an electroplating factory, who had been suffering from the temporal lobe epilepsy for 24 years and from hypertension for 2 years, took an unknown amount of potassium cyanide apparently over the lethal dose, in an attempt to commit suicide. He was treated successfully and survived without any neurological sequelae. The electroencephalograms and the nature of the seizures were not different before and after the poisoning. The T2-weighted magnetic resonance images at 9 and 51 days after the poisoning showed bilateral elevation of signals in the caudate nuclei and the putamina. At the 143th and 286th days. T2-weighted high-resonance areas were restricted to the lateral portion of the putamina. The T1-weighted images at the 51st day showed abnormal signal elevations in both putamina, while those of 9th, 143th and 286th days were mainly normal. Selective vulnerability of the putamen and the caudate nucleus may be due to their specific structural properties of high oxygen and glucose utilization, and enzyme distribution. Both chronological changes of striatal damage and the absence of neurological sequelae in this patient suggest the possibility that anti-epileptics and a calcium antagonist played a neuroprotective role in the acute cyanide intoxication. PMID- 8218430 TI - Psychotic and nonpsychotic bipolar mixed states: comparisons with manic and schizoaffective disorders. AB - We studied 259 female inpatients with bipolar spectrum disorders, of whom 26 (10%) were schizoaffective. Of the remaining 233, 61 (27%) met our conservatively set criteria for index mixed episodes (simultaneous presence of depressive and manic syndromes). These patients with rigorously defined mixed states were, in turn, about equally divided between psychotic and non-psychotic subgroups. The psychotic mixed patients (n = 32) were closer to the bipolar I pattern, and more often seem to come from a familial background of psychotic mood disorders; the nonpsychotic mixed patients (n = 29) conformed more closely to the bipolar II pattern, and more often had a hyperthymic and cyclothymic temperament and a family background of non-psychotic disorders and substance abuse. A three-way comparison between psychotic manic (n = 24), psychotic mixed (n = 32), and schizoaffective (n = 26) patients revealed few significant differences in temperamental, familial and course patterns. As expected, psychotic manic patients more often arose from a hyperthymic base and pursued a predominantly manic course; psychotic mixed patients were less likely to arise from such a base and more likely to pursue a mixed course. Finally, schizoaffective had earlier age at onset and longer duration of illness, suggesting that these patients had a more severe illness. Otherwise, interepisodic social adaptation was comparable in the three psychotic groups. The findings overall suggest that the presence of psychosis had relatively little impact on mixed states, which appear more based on temperamental characteristics. PMID- 8218431 TI - Elevated Le(y) antigen expression on T-lymphocytes in schizophrenic patients. AB - Le(y) is a carbohydrate determinant of membrane glycoconjugates and is expressed in some tumor and embryonic cells. On T lymphocytes, it is known that human immunodeficiency virus (HIV)-infected human lymphocyte T-cell lines express elevated Le(y) antigen and AIDS patients show the highest Le(y) expression in T lymphocytes at lower CD4/CD8 ratio. Later, a comparative elevation of Le(y) expression on T-cell subsets has been noticed to be mainly present in patients with viral diseases, such as acute and chronic hepatitis, implying an association of the highest Le(y) expression with viral infection. We found that Le(y) antigen was most expressed in both CD4+ and CD8+ subsets of peripheral T lymphocytes in hospitalized schizophrenic patients. On the other hand, atypical lymphocytes with stimulated morphology are known to appear in the blood circulation of schizophrenic patients. Similar atypical lymphocytes have also been described in viral and autoimmune diseases. Two possibilities have been discussed: viral association in the pathology in some schizophrenic patients; and immunological abnormalities including environmental effects under hospitalization on immune status, since normal controls (staff in psychiatric hospitals) showed higher Le(y) expression than normal controls under non-psychiatric circumstances. PMID- 8218432 TI - The key relative's impact on treatment and course of alcoholism. AB - One hundred alcoholics participated in a 6-week inpatient and a 6-week outpatient therapy programme and a 6-month and 18-month follow-up. Major goals of the study were a descriptive analysis of the course of illness over time, the evaluation of the effects of therapy in general and concerning the specific effects of additional (A) systematic inclusion of the key relative versus (B) systematic involvement in self-help, and identification of predictors for relapse. While therapy as such was quite effective and resulted in significant changes in symptomatology and the scores on personality scales, the additional involvement of the key relative showed no substantial additional treatment effects. Partnership interactions showed a deterioration during therapy, with temporary increased frictions. Based on conservative calculations, 40% of all patients remained abstinent until the 6-month follow-up and 30% until the 18-month follow up. PMID- 8218434 TI - Impact of genetics on toxicity testing, introductory remarks. PMID- 8218433 TI - The Zurich study. XX. Social phobia and agoraphobia. AB - The problems in association with agoraphobia and social phobia were examined in an 11-year prospective longitudinal study of a Swiss cohort of young adults. The weighted prevalence rates according to DSM-III were 2.9% for agoraphobia and 3.8% for social phobia. Although the problem of agoraphobia was greater in females, an equal sex ratio was observed for social phobia. There was a significant degree of comorbidity between the two subtypes of phobia, with females exhibiting a significantly greater frequency of co-occurrence of both disorders than males. The course of the two disorders was quite similar. In general, subjects with both disorders reported a more severe course. Assessment of comorbidity of phobias and other disorders revealed that agoraphobia was most significantly associated with extended neurasthenia, sexual problems, and the consumption of cannabis. On the other hand, social phobia was associated with other disorders than agoraphobia, with the strongest associations emerging for simple phobia, extended insomnia, and alcohol abuse. These findings support the validity of the distinction between different subtypes of phobia. The longitudinal analysis revealed that also phobia in general was not stable at the diagnostic level phobic symptoms were quite persistent across time. PMID- 8218435 TI - Toxicity testing and genetic quality control. AB - The genetic background of animals plays a major role in the outcome of toxicity tests. The use animals with a defined and standardized genetic variation as opposed to animals from an outbred strain may improve the quality of the tests and may reduce the numbers of animals to be used. In order to achieve this, animals from distantly related inbred strain (and their F1 hybrids) should be matched up in test and control groups (block design). The genetic distance between strains can be estimated by comparing the genetic profiles of strains which have been characterized for a set of monogenic marker genes. The establishment of the genetic strain profiles is also necessary when selecting the marker genes which are to be used for the genetic quality control of inbred strains. DNA markers, in particular the highly polymorphic SSLP's (microsatellites) are the most appropriate ones for this purpose. PMID- 8218436 TI - Genetic variation in outbred rats and mice and its implications for toxicological screening. AB - There are two basic types of laboratory rodent used in toxicological screening. Isogenic (inbred) strains are rather like clones of genetically identical individuals whereas outbred stocks are usually more variable, though the amount of variability depends on the previous history of the colony. In some cases outbred stocks may be genetically quite uniform. Many different strains of both types are available. Both types and a variety of strains are used for toxicological screening. There is clear evidence of important genetic variation both in spontaneous disease and in response to toxic agents, yet little account is taken of this in choosing suitable animals. Three options appear to be available. The first is to ignore genetic variation and use a single isogenic strain. However, if the strain happens to be insensitive to the test chemical, a toxic chemical may be judged to be relatively safe. The second option would be to synthesize a genetically heterogeneous stock by crossing two or more strains. However, this could lead to both increased false positive and false negative results as experimental "noise" either obscures true treatment effects, or is mistaken for a treatment effect. The third option is to use more than one strain, but without increasing the total number of animals used. This would provide a broad range of genotypes, so reducing the chance that they are all insensitive, without increasing experimental noise. This appears to be the only sensible way of broadening the genetic base in toxicological screening. Where strain differences are found, they may provide a tool for studying toxic mechanisms, which may be helpful in extrapolating to human populations. PMID- 8218437 TI - Multiple levels of response in carcinogenicity bioassays: regulational variation among viable yellow (Avy/-) mice. AB - Within genetically identical inbred and F1 hybrid test animal populations there exist subpopulations with different levels of sensitivity to induction of toxic endpoints, e.g., neoplasms, in response to toxicant exposure. These subpopulations differ from each other by other phenotypic characteristics as well. Presumably, these differences reflect alterations in the quantitative expression of some genes. These alterations are most probably directly or indirectly induced by subtle prenatal, neonatal or postnatal changes in endogenous microenvironmental conditions or factors. Such subpopulations have been identified within a population of agouti A/a and mottled yellow Avy/A (C3H x VY)F1 hybrid male mice. In these subpopulations differential body weight gain and formation of multiple liver adenomas in response to phenobarbital treatment were correlated with altered constitutive and inducible hepatic drug-metabolizing isozyme activities. These subpopulations could be identified by body weight as early as weaning age. In a different population of (YS x VY)F1 hybrid female mice, three phenotypes with different patterns of sensitivity to liver and lung tumor formation form visually separable phenotypic subpopulations by postnatal day 7. Two of these phenotypes, obese mottled yellow and lean pseudoagouti, are genetically identical (genotype: Avy/a), while the third phenotype, lean black a/a, differs from the others by just the Avy allele. The yellow and pseudoagouti mice, fed lindane (gamma-hexachlorocyclohexane) for 24 months, differed with respect to liver tumor incidence but had similar incidences of lung tumors. In contrast, the black mice, fed lindane, were totally resistant to both types of tumors. Analyses of phenotypic variation within other inbred or F1 hybrid populations have identified analogous subpopulations. In carcinogenicity assays this phenotypic variability can be used to mimic differential sensitivity to toxicant exposure among individuals in human populations. Data obtained from such phenotypic subpopulations should assist in improving risk assessment efforts. PMID- 8218438 TI - Pros and cons of transgenic mouse mutagenesis test systems. AB - Over the last two years, first results of transgenic mouse mutagenicity assays have appeared in the literature. If sufficiently sensitive, this new in vivo transgenic mouse assay may be the first approach that allows us to measure frequencies of induced point mutations for any suspected target organ in mice. It may also be useful as a routine assay and could complement or replace the mouse spot test or the specific locus test. Different transgenic mouse strains exist that can be employed for this assay. This review summarizes some of the data that were generated with this promising novel in vivo test system. Remaining problems with its sensitivity and the question of the optimal test protocol are discussed. PMID- 8218439 TI - Variations in disease in inbred and outbred strains of rodents. AB - Risk assessment from toxicity testing is difficult because of interanimal variability and high levels of spontaneous pathology in rodents. Genetically defined animals might improve risk assessment by reducing the effects of these two factors. Data is presented on disease patterns in mice from an outbred colony of Swiss albino Alpk:APfCD-1 mice, and inbred mouse strain C57Bl/10JfCD-1/Alpk, and an outbred rat colony Alpk:APfSD (Wistar derived). All of the strains have been bred, maintained and used continuously, in one laboratory, for 20 to 30 years. The data is derived from control animals in toxicity tests completed between 1960 and 1990, chiefly from oncogenicity studies. The results indicate that the major diseases, particularly the most common tumours in each strain, liver tumours in the outbred mouse, lymphomas in the inbred strain, and pituitary adenomas in the outbred rat, increase in incidence with time. Renal disease also increases in the outbred rat. This increase has been shown to be due to overnutrition. The effects of overnutrition can override the genetic characteristics of strain, and risk assessment is, therefore, unlikely to be improved by the use of genetically defined animals alone. The environmental conditions of toxicity experiments must also be defined and controlled. PMID- 8218440 TI - The utilization of quantitative trait loci in toxicogenetics. AB - With the increasing number of marker loci available in mouse, the traditional method of recombinant inbred strains can be extended to searches for quantitative trait loci (QTL) influencing continuously distributed phenotypes. These loci have effect sizes too small to be easily detectable by conventional single-locus techniques. Collective, several QTL may account for a substantial proportion of the phenotypic variability. Prospective advantages of location of QTL in toxicology-relevant phenotypes include opportunities for the study of mechanism, prospects of generating animal models by genotypic selection, study of the dynamics of gene interaction, and guiding the search for homologous genes in human beings. PMID- 8218441 TI - Impact of pharmacogenetics on toxicological studies. Statistical implications. AB - Genetic differences in response to chemicals are probably ubiquitous. The implications of such genetic differences for the design of toxicological experiments is reviewed. The inclusion of genetic differences as factors in factorial experimental designs is illustrated by an experiment to investigate differences between inbred strains of mice in the length of anaesthesia following the administration of pentobarbitone to control and phenobarbitone pre-treated animals. The effects of including genetic differences as a factor in the standard toxicological studies such as the long-term rodent carcinogenicity bioassay (LTRCB) are reviewed. Such designs are likely to result in more chemicals being identified as carcinogens based upon the criteria of a positive result in the LTRCB. However, they are unlikely to provide any improvement in the estimation of risk to the human population from low level exposures to the chemicals because of the limitations of the existing extrapolation methods. Information on the degree of genetic variability in response to chemical exposure should, though, help in the more qualitative biologically-based risk assessment approaches favoured by some toxicologists. The presence of genetic differences in response also provides potential models for investigation of the mechanisms underlying toxicological responses. PMID- 8218442 TI - Will financial exigency in education and health care promote reform or anarchy? PMID- 8218443 TI - CRNAs caring for America. PMID- 8218444 TI - Institutional survey of nurse anesthesia practice in patients receiving opioids via patient-controlled analgesia. AB - This preliminary study determined certified registered nurse anesthetist (CRNA) practice experience and educational needs in the preoperative evaluation of patients using patient-controlled analgesia (PCA) for chronic and cancer pain management. A convenience sample (N = 29) of CRNAs practicing in a university teaching hospital completed the surveys developed by the investigator. Survey items related to CRNA experience with management of patients using PCA preoperatively, PCA modes of opioid delivery, and use of adjuvant medication for chronic and cancer pain patients. Results of the study indicated that 79% of CRNAs reported experience in administration of anesthesia to one or more patients who used PCA preoperatively. However, only 32% of CRNAs surveyed reported knowledge of the modes of opioid delivery available. Results also indicated that 48% of CRNAs were not familiar with adjuvant medications (ie, tricyclic antidepressants, benzodiazepines, steroids, and anticonvulsants), which are often prescribed in combination with opioids in chronic pain management. The respondents reported use of a variety of methods in handling opioid and infusion devices for patients using PCA preoperatively. Fifty-two percent of CRNAs disconnected the infusion and discarded the opioid preoperatively. Fourteen percent reported leaving the PCA device connected to the patient for use perioperatively or for continued pain management postoperatively. Based upon the findings of this preliminary study, CRNA education in management techniques for the use of PCA infusions in chronic and cancer pain is recommended. PMID- 8218445 TI - Scope of nursing practice and business relationships between nurses and physicians in California: Part 1. PMID- 8218446 TI - Anesthetic management for emergent cesarean section in a patient with penetrating head injury. AB - Anesthetic intervention in the parturient is challenging as a consequence of the anatomic and physiological changes of pregnancy. The added encumbrance of central nervous system injury requires careful consideration for the selection of anesthetic agents and the management of anesthetic technique, with emphasis on the maintenance of maternal neurological function and fetal well-being. The authors discuss the selection of anesthetic agents and management of anesthesia in an acute head-injured parturient who required emergent intervention for the delivery of a premature infant. PMID- 8218447 TI - Avoiding the "school paper style" rejection. AB - These style aspects are developed slightly differently by each journal or book publisher, so investigate how each is handled in your target publication. Through these steps and the advice of your editor, you can develop a professional style that communicates your professional ideas as the expert you are. PMID- 8218448 TI - A survey of the costs of flexible endoscope cleaning and disinfection. AB - A questionnaire was developed and sent to the 860 members of the Society of Gastroenterology Nurses and Associates Lab Management Special Interest Group. Of the 98 (11%) completed responses, the average per-procedure price for cleaning one flexible endoscope was $39.13 for manual disinfecting and $40.56 using an automatic disinfector. Staff costs, including those attributable to cleaning related delays, accounted for the largest single component of the overall cleaning costs (44%). Cleaning-related damage and maintaining an inventory of endoscopes to offset the effects of reprocessing on procedure scheduling were also found to significantly contribute to cleaning costs. PMID- 8218449 TI - Recruitment and retention of GI nurses: hiring, firing, and surviving. AB - Nursing turnover is costly for GI units, both financially and emotionally. The emphasis at Duke University Medical Center is changing from recruitment of GI nurses to searching for methods of retaining staff and building team morale. Recruitment and retention survey results are discussed in this article and retention strategies presented. PMID- 8218450 TI - The development of a position statement using the Delphi technique. AB - The need to develop practice-related documents in an accurate, efficient, and economical manner is the responsibility of the Board of Directors of the Society of Gastroenterology Nurses and Associates (SGNA). When the results of large, randomized, controlled, clinical trials are available, documents can be based on the information published in scientific literature. GI nursing, however, is in a novice phase regarding controlled research trials; thus, other methods of obtaining reliable information are required. The Delphi technique was selected to obtain the consensus of experts. The Delphi technique enables a free and open exchange of ideas while respecting the economics of a deficit budget. This article describes the Delphi process and the manner in which it was used to prepare the SGNA position statement, "Responsibilities of the Gastroenterology Registered Nurse related to Conscious Sedation." PMID- 8218451 TI - Managing patient stress in endoscopy. AB - Most patients experience a certain degree of stress as they prepare for and undergo endoscopy procedures. The stress they experience is correlated to Hans Seyle's General Adaptation Syndrome theory in this article. Stressful events that occur pre-, intra-, and postprocedure are identified. Examples of patient coping skills are discussed. Several nursing interventions such as patient teaching, relaxation techniques, and communication skills are described. All of these interventions assist the nurse in promoting a positive outcome for the patient. As a patient experiences a positive outcome from a stressful event, coping mechanisms are strengthened and developed. These coping mechanisms enable the patient to adapt to future stressors. PMID- 8218452 TI - Conscious sedation for endoscopy in the pediatric patient. AB - This article defines conscious sedation and ASA patient classification, reviews the pharmacologic and behavioral issues in children, and describes the essentials for successful sedation. It provides only guidelines as each patient requires individual attention. Clearly, conscious sedation works well in children for most endoscopic procedures and with continued refinement will become the method of choice. PMID- 8218453 TI - Computerized videoendoscopy. PMID- 8218454 TI - The impossible percutaneous endoscopic gastrostomy: teamwork and timing made the difference. PMID- 8218455 TI - Fentanyl citrate (fentanyl sublimaze). AB - Fentanyl (Sublimaze) is a synthetic opioid used as a combination drug for conscious sedation in patients requiring endoscopic diagnostic and therapeutic procedures. Fentanyl is generally used in place of meperidine (Demerol) in combination with droperidol (Inapsine) and midazolam (Versed), creating neuroleptanesthesia for patients undergoing procedures that require patient cooperation. PMID- 8218456 TI - Evaluation of stage 4 neuroblastoma patients by means of MIBG and 99mTc-MDP scintigraphy. AB - In a group of 22 patients with a stage 4 neuroblastoma, MIBG and 99mTc-MDP scintigraphy and radiological skeletal survey were performed at diagnosis to assess the presence of metastatic skeletal disease. In 20 out of 22 patients the MIBG scan was repeated during follow-up at a time when maximum tumoral regression was expected, i.e. after 3-4 cycles of chemotherapy; scan results were correlated to clinical and laboratory data. At diagnosis MIBG scan showed bone involvement in 19/22 patients, 99mTc-MDP in 20/22 and radiological skeletal survey in 11/22. In 1 patient only marrow aspirate revealed diffusion of disease beyond the primitive lesion. A total of 117/161 (72%) bone lesions were detected by MIBG, 89/161 (55%) by 99mTc-MDP and 47/161 (29%) by radiological skeletal survey. MIBG scintigraphy revealed bone marrow involvement in 11/22 patients in whom either marrow aspirate or bone biopsy were positive. In 5 patients 14 soft tissue lesions were also discovered and all but one primitive lesion accumulated MIBG. Although MIBG scan detected a greater number of bone lesions than 99mTc-MDP, in two patients in whom MIBG scan was negative 99mTc-MDP revealed the presence of bone involvement. Therefore we conclude that 99mTc-MDP scan is necessary to fully assess bone involvement in neuroblastoma at diagnosis. When MIBG scan was repeated after chemotherapy there was a general reduction of the number of detected lesions and in 8/17 patients both bone metastases and marrow involvement could no longer be detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218457 TI - Functional evaluation of renal transplants with scintigraphy. AB - A variety of techniques have been employed to assess renal function and its evolution after transplant surgery. Since initial perfusion studies are easy to perform, one may be tempted to rely on 99mTc-diethylenetriaminepentaacetic acid (DTPA) scanning alone. Some discrepancies have been observed between perfusion studies and clinical outcome of the renal transplant patients however. We therefore decided to evaluate both 99mTc-DTPA and 131I-hippuran renal scanning in 28 renal transplant patients. Sixty 99mTc-DTPA perfusion and 131I hippuran scintigraphies were performed using a same-day protocol. The examinations were repeated in 14 patients at weekly or monthly intervals to monitor the clinical trend of these patients. The results of this study indicate that, for early detection of the kidney problems, 131I-hippuran scintigraphy was superior to 99mTc-DTPA perfusion scans, but for the proper clinical management of renal transplant patients, both procedures should be utilized. PMID- 8218458 TI - Ischemia on effort is not a determinant of stunned myocardium in man: a radioisotopic study based on quantitative evaluation of ventricular dynamics. AB - To assess whether myocardial stunning occurs following brief episodes of effort ischemia, ventricular function was assessed by radionuclide angiography in 29 patients with coronary artery disease. No patient had evidence of previous myocardial infarction. Patients were divided into two groups according to presence of single (14 patients, Group 1) or multi-vessel (15 patients, Group 2) coronary artery disease. Equilibrium radionuclide angiocardiography was performed in the left anterior oblique projection by a small field-of-view gamma-camera. Acquisition were performed at baseline, at peak exercise, then again at 1 and 5 minutes of the recovery phase. For each acquisition, ejection fraction, peak filling rate and wall motion index were measured and compared. No difference in baseline and stress measurements was found between Group 1 and Group 2, except for the wall motion index that was more impaired during ischemia in patients of Group 2. Global and regional indexes of ventricular function did not show significant differences also in the two recovery periods when compared to the relative baseline values. Transient ischemia caused by an increase of oxygen demand did not reproduce the phenomenon of systolic and diastolic stunning observed in animal experiments, although in all patients the ischemia was of sufficient duration and severity to induce transient ventricular dysfunction. PMID- 8218459 TI - Evaluation of CEA, TPA, CA 15-3, CA 549 and TPS in the monitoring of metastatic breast cancer. AB - Monitoring the response to treatment in relapsed breast cancer patients is one of the chief uses of tumor markers. Thus far the carcinoembryonic antigen (CEA) tissue polypeptide antigen (TPA)-breast cancer associated antigen 115 D8/DF3 (CA 15-3) association has been routinely used to follow-up breast cancer patients. We have found that TPA reflects the response to treatment much better than CEA and slightly better than CA 15-3. Recently carcinoma associated antigen 549 (CA 549) and tissue polypeptide specific antigen (TPS) have been reported to be highly sensitive tumor markers for breast cancer. TPS is claimed to be particularly suitable for monitoring the response to treatment because of its more specific assessment of proliferation activity. Therefore, in 13 relapsed patients with prolonged follow-up and detailed clinical-instrumental information, the mean percentage of samples with high CEA, TPA, and CA 15-3 values and their expressions were compared with those of CA 549 and TPS. All markers were also evaluated in terms of their correspondence with the evolution of disease. The correspondence with clinical-instrumental behaviour was scored absent (0), poor (1), good (2) and very good (3) by three different observers. Other more suitable associations than those already used were also investigated. It was found that CA 15-3 and CA 549 were expressed more often (92%) than TPS (85%), TPA (60%) and CEA (46%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218460 TI - HIV and AIDS in Asia and the Pacific. PMID- 8218461 TI - Levels of HIV risk behaviour and AIDS knowledge in Thai men having sex with men. AB - Although many of the earliest cases of AIDS and HIV infection in Thailand were men who had sex with other men (MHSWM), transmission by heterosexual intercourse and needle sharing rapidly became dominant. This resulted in comparatively little attention being given to studies of risk behaviour and seroprevalence in groups of MHSWM with a consequent lack of information about these populations relevant to designing effective interventions. In the Partner Relations Survey, 3.3% of male Thais described their orientation as bisexual or homosexual, most probably an underestimate of the occurrence of same sex behaviour in Thai males. This paper briefly reviews the situation and presents results from a survey in the northeast of Thailand among men who have sex with men. Substantial levels of risk behaviour were found in MHSWM in the Northeast, with high rates of partner exchange and low levels of consistent condom use in insertive and receptive anal intercourse. Significant defects in AIDS knowledge existed implying a strong need for enhanced and expanded interventions in this community. Factors relevant to the design of interventions are highlighted and recommendations for further studies of MHSWM in Thailand are presented. PMID- 8218462 TI - HIV infection among injecting drug users in north-east Malaysia, 1992. AB - Human immunodeficiency virus (HIV) has spread widely among injecting drug users (IDUs) in countries to the north and west of the 'Golden Triangle' region of South-East Asia; it is likely to have spread southwards to Malaysia as well. In order to assess HIV seroprevalence among IDUs in north-east Malaysia and describe risk factors for HIV infection in this population, we performed a cross-sectional seroepidemiological study among 210 IDUs recruited at the detoxification ward of the General Hospital in the capital city of the north-eastern Malaysian state, Kelantan. Subjects were sequential entrants to the detoxification ward, interviewed about HIV risk behaviour, and tested for antibody to HIV and to syphilis. Nearly a third (62/210, 30%) of these IDUs were HIV seropositive. Three quarters (159/210) had travelled to Thailand in the preceding 5 years, of whom 32% (51/159) were HIV seropositive; this was associated with injecting in Thailand, but not with sexual contact there. Of those who had not left Malaysia in the preceding 5 years, 26% (11/43) were HIV seropositive, a rate not significantly different from those who had travelled. Travel within Malaysia was common (144/210, 69%) among IDUs interviewed, as was unsafe injecting and unsafe sexual behaviour (20% had shared injecting equipment and 21% had had unprotected intercourse) in other states. In every locale, rates of unsafe injecting behaviour were high (55% sharing in last month), even among those who knew they were HIV infected, and rates of condom usage were low (93% of 160 sexually active IDUs had never used a condom). Syphilis was not associated with HIV infection, but with contact with Thai prostitutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218463 TI - Socio-economic impact of HIV/AIDS in the Philippines. AB - This paper analyses the potential socio-economic impact of HIV disease in the Philippines, with focus on the situation of two vulnerable populations: overseas contract workers and sex workers. The potential impact of HIV disease is examined in the context of recent developments in the Philippines, including the economic recession, widespread poverty and income inequality. The contributions of overseas workers and sex workers are then reviewed, both at the macro- (national) and micro- (household) levels. The impact is examined in terms of lost income, costs of medical care and sociopolitical disruption. PMID- 8218464 TI - AIDS and STDs: risk behaviour patterns among female sex workers in Bali, Indonesia. AB - This study investigated AIDS and STD knowledge, risk behaviour patterns and condom use among three distinct groups of female commercial sex workers (CSWs) in Bali, Indonesia. Individual in-depth interviews were conducted with 71 female CSWs. These CSW groups differ in the prices they charge, their places and modes of employment, educational backgrounds, levels of AIDS and STD knowledge, number of clients served and levels of condom use. Knowledge of the routes of transmission and appropriate prevention practices is low among all groups, and despite significant differences in their number of clients and their condom use, all groups report high levels of STD symptoms. Although HIV seroprevalence rates are currently low in Indonesia, high risk sexual behaviour patterns place all three groups of CSWs and their clients at great risk of infection. Interventions targeted to specific groups of CSWs and clients should be undertaken as soon as possible, including educational activities utilizing peer educators, condom promotion and distribution, together with improved STD diagnosis and treatment for CSWs and their clients. PMID- 8218465 TI - HIV-related knowledge and attitudes among medical students in China. AB - A modified version of the 'WHO/KABP Questionnaire for Students' was administered to 302 students at a medical university in China. The instrument included items to assess the students' demographic background, knowledge of AIDS/HIV, attitudes about AIDS, as well as towards people infected with HIV, those groups commonly labelled as 'high risk' and toward sources of information. The average score on the knowledge scale was 80% correct. There was a substantial disparity in knowledge between how HIV is transmitted and how HIV is not transmitted--90% of the former items were answered correctly, while only 72% of the latter were answered correctly. Over 40% of the sample blamed prostitutes for AIDS in China, whereas 22% blamed drug addicts and 6% blamed homosexuals. Two-thirds of the sample indicated that they thought people with AIDS got what they deserve. About one-third of the sample supported quarantine measures as well as keeping infected students out of classrooms. Nearly half of the sample indicated that they did not trust any of the official sources of health information we asked about and 27% said that they thought the government was concealing information about AIDS. PMID- 8218467 TI - Female streetworker--prostitutes in Glasgow: a descriptive study of their lifestyle. AB - The objective of this study is to describe the lifestyle of a group of female prostitutes. The collection of information was achieved by: (i) using a self administered questionnaire; and (ii) conducting conversational type interviews. Of 85 women attending a health care drop-in centre for female street prostitutes in Glasgow, 63 completed the questionnaire and 72 participated in conversational interviews. For 63 women the mean age of commencement of prostitution was 21 years. Fifty-one (81%) were injecting drug users, their most commonly used drugs being heroin and temazepam. They worked a mean of 5.5 evenings per week and provided sexual services to a mean of 6.4 clients per working day. Less than half of these services were estimated to be vaginal intercourse. While 59/60 women indicated that they always used condoms during vaginal intercourse, this only applied to commercial sex; only 8/47 (17%) always used condoms with their regular sexual partners. Unconventional sexual services, e.g. voyeurism and physical abuse, were commonly provided and clients were often violent. A typical female streetworking-prostitute in Glasgow was aged 25, unemployed, an injecting drug user and had commenced prostitution 4 years before. Her knowledge of HIV/AIDS was good and for vaginal intercourse she almost always used condoms with clients, though probably not with her regular partner. Her main concern was likely to be violence from clients. PMID- 8218466 TI - HIV infection among injecting drug users in Asia: an evolving public health crisis. AB - Injecting drug use is being reported from an increasing number of Asian and other Third World countries. HIV continues to spread globally among and from populations of injecting drug users (IDUs), although the rate of spread appears to have slowed down recently in some industrialized countries. Asia produces two thirds of the world's supply of opium. In recent years the rapid development of new illicit drug trade routes in efforts to evade detection by law enforcement authorities has exposed new populations in Asia to drug injecting and, thus, the risk of HIV infection. Epidemic spread of HIV has recently commenced in some Asian countries among injecting drug users, and others are at substantial risk of an HIV epidemic among their IDU populations. The speed of spread and the consequences of HIV infection among IDUs in Asian and other Third World countries are even more profound than in western countries. Asian countries attempting to control this component of the epidemic often have greater difficulty than industrialized countries because of their proximity to drug producing areas, scarcity of resources and a greater likelihood of pragmatic policies conflicting with traditional values. Vigorous efforts are urgently required at both a national and international level to raise awareness of the consequences of an uncontrolled epidemic of HIV among IDUs in Asian and other countries, and to support the implementation of policies which are likely to reduce the spread of HIV. PMID- 8218468 TI - Investigation of motivational and behavioural factors influencing men who have sex with other men in public toilets (cottaging). AB - One-hundred-and-thirty-four individuals engaging in cottaging returned postal questionnaires. The sample was mainly urban and gay identified. Cottagers reported that cottaging was one way of meeting partners amongst a range of others they used. Most enjoyed it and felt in control of their cottaging. The majority of cottagers engaged in safer sexual activity, but there were a significant number who engaged in unsafe sexual activity last time they cottaged. Of those who had been voluntarily tested in the past and reported their serostatus, 23% were seropositive. Unsafe sexual activity was unrelated to whether tested or not, known serostatus or knowledge of the risks of transmission. PMID- 8218469 TI - AIDS epidemic in Kagera region, Tanzania--the experiences of local people. AB - This study is part of a collaborative study of HIV infection and AIDS which was launched in 1987 in the Kagera region, Tanzania. This region is characterized as one of the areas most affected by the AIDS epidemic. In order to describe and analyse the epidemiology of HIV infection in the area and also to contribute to the intervention process, a long-term population-based project was initiated. The study was launched in January 1989 as an in-depth behavioural study to describe the experiences of the local people of the AIDS epidemic in the region. The specific objectives were to determine the people's attitudes, perceptions, responses and norms relevant to AIDS-related problems. The data were collected through tape recorded interviews, focus group discussions and direct observations of risk behaviour. The interviews were conducted in 10 villages, in urban and rural Bukoba as well as in Muleba districts. In each village five households were selected and visited once a week for about 6 months. The focus group discussions were held mainly with young males, females, married women and married men, elders and religious leaders, government and party leaders, and other key informants. Perceptions, attitudes and patterns of behaviour among the local people are described in the context of the HIV transmission in the area. The descriptions give answers to questions like: How do people perceive and interpret AIDS? How do they react to AIDS? How do they judge causes and risks? What are the attitudes to people with AIDS and those suspected to have AIDS? What are the implications of these values in affected communities? PMID- 8218470 TI - Staff distress among haemophilia nurses. AB - To investigate the severity, sources, and means used to cope with the distress experienced by haemophilia nurses as a result of the widespread infection with Human Immunodeficiency Virus among haemophiliacs, we collected anonymous questionnaire data from all nurses in the Haemophilia Nursing Network Directory, compiled by the National Haemophilia Foundation in June, 1990. Questionnaires were returned by 136 of the 181 (75%) nurses in the sample. Over 50% of the sample gave distress responses to 15 of 44 statements. Areas associated with the greatest distress were: (1) Failure of patients to take steps to prevent transmission of HIV; (2) Fear of getting infected, and (3) the repeated loss experienced as patients died from infection. Nurses working with haemophiliacs for 11-15 years were particularly vulnerable to feelings of guilt for having participated in the treatment that resulted in HIV infection. Fear of contagion and distress from patient deaths were mutually exclusive ways of reacting to HIV in haemophiliacs. Looking for a new job was related to all major sources of distress. Interaction with peers was perceived as being the most useful source of emotional support. PMID- 8218472 TI - World Health Organization Global AIDS statistics. PMID- 8218471 TI - The Seattle appropriate level of care survey: health status and health services use in ambulatory persons with AIDS. AB - We surveyed 77 persons with AIDS, their physicians and their social workers during the autumn of 1987 to ascertain health status and to quantify use of health services in Seattle, Washington. Participants included the majority (59%) of persons living with AIDS in the area. Information was gathered regarding demography, health status, functional status, medical history and the use of health services. The validity of self-assessed general health was corroborated by the physician-rated Karnovsky score (kappa = 0.59), by social worker assessment (kappa = 0.41), and by correlation with functional status (r = 0.6-0.8). We found more frequent use of health services (categorized into skilled services, chore services and physician services) among AIDS patients who were dependent in basic and instrumental daily activities, had low income, had poor self-assessed general health, lived alone or lacked an available support person at home. These associations persisted in multivariate analyses, and accounted for 6-23% of the variability in service use. We conclude that health and functional status of persons with AIDS can be estimated via mailed questionnaires and accounts for a modest amount of the variability in use of health services. PMID- 8218473 TI - Strategies for pH gradients' optimization. AB - A few problems arising when optimizing the composition of the mixtures to be used for IPG casting with a two chambers mixer are discussed. The behavior in the composition space of a number of objective functions is described by simulation. This allows the formalization of rules to be followed for finding the initial guess required to start the optimization algorithm and for directing and limiting the search of the objective's minimum. the results of the simulation show that a fully automatic gradient computation and optimization is possible. PMID- 8218474 TI - Two-dimensional gel electrophoresis of major cytosolic proteins derived from spleen mononuclear cells of normal and leukemic rats. AB - Proteins from leukemic spleen cells derived from a F344 rat transplant model were investigated by 2D gel electrophoresis. The cell line was maintained in vivo by serial transplant of mononuclear spleen cells from leukemic donors into syngeneic recipients. Cytosolic proteins from mononuclear cells (MNC) were isolated from spleens of normal and leukemic rats and separated by electrophoresis. Replicate data from silver-stained gels for each preparation were compiled into Master Images using image analysis algorithms in order to characterize the normal and leukemic protein profiles. Comparative analysis showed a total of 458 proteins that were reproducibly detected in normal MNC, while almost twice the number of proteins (828) were found in leukemic MNC, suggestive of the more mitotically active tumor cells. Profile analysis showed that normal and leukemic preparations shared 228 common proteins, with 600 proteins observed only in leukemic MNC, and 230 proteins found only in normal MNC. Differences in protein patterns between normal and leukemic MNC in rats probably reflects a shift in spleen leukocyte populations and a relative induction of gene expression in leukemic MNC as compared to the normal MNC. PMID- 8218475 TI - Concanavalin A affinity immunoelectrophoresis of slowly migrating glycoproteins by chemical charge modification. AB - A method for the study of slowly migrating glycoproteins by lectin-affinity immunoelectrophoresis is described. The principle of the method is to modify chemically the polypeptide part of the glycoprotein in question to increase the net negative charge of the molecule without affecting the carbohydrate parts. In a model experiment, desialylated human alpha 1-acid glycoprotein is modified and it is shown by lectin affinity immunoelectrophoresis that glycan-bound sialic acid does not influence the binding of human alpha 1-acid glycoprotein to concanavalin A. Additionally, the method is used to study the carbohydrate-based microheterogeneity of slowly migrating mouse serum glycoproteins, and hitherto undetected microheterogeneity inherent in mouse transferrin and mouse haemopexin is detected and described in normal and inflammatory mice. PMID- 8218476 TI - Automated DNA sequencing: an image processing approach. AB - An automatic DNA sequencing analysis system has been developed by Scanalytics/CSPI. The strategies used to solve some of the common problems in the automation of DNA sequencing systems will be discussed. Algorithms developed include fast image background correction, automatic base detection, resolution enhancement by deconvolution, desmiling and artificial intelligence algorithms for sequence interpretation. PMID- 8218477 TI - Enhanced detection of PCR products through use of TOTO and YOYO intercalating dyes with laser induced fluorescence--capillary electrophoresis. AB - Recent developments in the chemical synthesis of DNA-binding dyes have enhanced detection of polymerase chain reaction (PCR) products by capillary electrophoresis. These dyes are dimers of thiazole orange (TOTO) or oxazole orange (YOYO) and have a very high binding affinity for DNA (Haugland, 1992). These dyes show enhanced fluorescence signals when they bind to double-stranded DNA and their fluorescence in the unbound state is almost zero, making them extremely useful in detecting minute (fg) quantities of DNA. We report here the utility of these dyes in DNA typing applications using a laser-induced fluorescence detector in conjunction with a capillary electrophoresis system. PMID- 8218478 TI - The molecular weights of twelve apolipoprotein(a) variants, determined using haptoglobin 2-2 polymer molecular weight standards. AB - Apolipoprotein(a) [apo(a)] variants were characterized in 398 sera by immunoblotting: (a) by molecular weight, using a haptoglobin 2-2 polymeric series as standards, and (b) by nomenclature, using serum pools containing previously characterized apo(a) variants as standards. The haptoglobin 2-2 standard curve (172-859 kDa) alleviates the necessity of obtaining molecular weights by extrapolation. Among the 398 sera, 40.2% had double apo(a) bands (54 phenotypes), 58.0% had a single apo(a) band and 1.8% were null (no bands observed). An inverse, though non-monotonic, relationship was observed between apolipoprotein(a) molecular weight and serum lipoprotein(a) [Lp(a)] concentration. Due to the large size of apo(a) and the relatively small increment between variants (15-16 kDa), molecular weight could not be used alone to characterize variants. Even with a CV of 3-4%, there was an overlap between variant molecular weight estimates. However, in combination with the identification of variants by comparison with standards, the haptoglobin 2-2 standard curve could be used to obtain mean molecular weight estimates for each variant. 12 distinct variants were identified among the sera, with apparent mean molecular weights of 314, 388, 410, 433, 454, 466, 503, 519, 528, 543, 553 and 572 kDa, respectively. These molecular weight estimates are consistent with the theoretical molecular weight range for apo(a) variants, calculated from sequence and carbohydrate analysis, of 238-643 kDa. PMID- 8218479 TI - Increased apolipoprotein-E concentrations in individuals suffering chronic low back syndrome identified by two-dimensional gel electrophoresis. AB - Non-biased screening of plasma proteins by two-dimensional gel electrophoresis from individuals suffering low back syndrome revealed a polypeptide spot that was increased 2-5-fold over the concentration found in normal control individuals. The apparent molecular weight (34-36 kDa) and pI (5.7) of this spot suggested that it might be apolipoprotein-E. Immunoblot analysis showed that the polypeptide was reactive with anti-apolipoprotein-E antibodies. N-terminal amino acid microsequence confirmed the identify of this polypeptide as apolipoprotein E. We have determined that elevated plasma levels of apolipoprotein-E is associated with inflammation and nerve damage. PMID- 8218480 TI - Chemically optimized antimyosin Fab conjugates with chelating polymers: importance of the nature of the protein-polymer single site covalent bond for biodistribution and infarction localization. AB - Murine antimyosin Fab fragment was conjugated with 111In-labeled N-terminal modified DTPA-polylysine using three bifunctional reagents: N-hydroxysuccinimide esters of 3-(2-pyridyldithio)propionic acid (SPDP conjugate), 4 (maleimidomethyl)cyclohexanecarboxylic acid (SMCC conjugate) and bromoacetic acid (BrAc conjugate) for potential localization of experimental myocardial infarction. Using various antibody preparations and a rabbit acute myocardial infarction model the following parameters were observed: (1) an in vitro antigen binding activity of SPDP conjugate = SMCC conjugate > BrAc conjugate, (2) a blood clearance rate of SPDP conjugate > BrAc conjugate > SMCC conjugate, (3) a liver and splenic accumulation of SPDP conjugate > BrAc conjugate > SMCC conjugate, and (4) the infarcted tissue activity showed an accumulation of SMCC conjugate > SPDP conjugate > BrAc conjugate. This study exemplifies the importance of rational chemical design of antimyosin Fab-chelating polymer conjugate for improved target tissue localization in vivo. PMID- 8218481 TI - Synthesis and binding of new polyfluorinated aryl azides to alpha-chymotrypsin. New reagents for photoaffinity labeling. AB - The preparation of several new, water-soluble, polyfluorinated aryl azide reagents for use in photoaffinity labeling studies is described. The ability of some of these reagents and their nonfluorinated controls to noncovalently bind to alpha-chrymotrypsin is reported. It is found that polyfluorination does not interfere with ligand binding. PMID- 8218482 TI - Functional peptide-polyurethane conjugates with extended circulatory half-lives. AB - Peptides containing the RGD sequence were covalently attached to an isocyanate containing polyurethane prepolymer and the biological properties of the complexes were evaluated. For the pentapeptide H2N-Tyr-Arg-Gly-Asp-Ser-OH (single-letter code, YRGDS), polymer conjugation lead to an increased half-life in the blood circulation of mice to > 10 h. The effect of covalent attachment of polymer on biological activity was examined in a related peptide, H2N-Gly-Arg-Gly-Asp-Ser Pro-Ala-Cys- OH (GRGDSPAC). Inhibition of B16-F10 melanoma cell attachment and spreading on plates coated with fibronectin by an RGD-containing peptide and polymer-conjugated GRGDSPAC was observed to occur at similar concentrations. We conclude that the conjugation of peptides containing the Arg-Gly-Asp motif to this polymer resolves previous problems of their rapid loss from the circulation, while still allowing retention of full biological inhibitory activity. PMID- 8218483 TI - Forskolin photoaffinity probes for the evaluation of tubulin binding sites. PMID- 8218484 TI - Synthesis, metal chelate stability studies, and enzyme digestion of a peptide linked DOTA derivative and its corresponding radiolabeled immunoconjugates. AB - By directly coupling a tetrapeptide to DOTA through an amide bond, we synthesized a novel DOTA derivative, DOTA-glycylglycylglycyl-L-p-nitrophenylalanine amide. We converted this new precursor bifunctional chelating agent to DOTA glycylglycylglycyl-L-p-isothiocyanatophenylalanine++ + and conjugated it to monoclonal antibody Lym-1. Serum stability studies show that the radiolabeled conjugates are kinetically inert under physiological conditions. The rates of loss of radiometals in human serum are 0.1 +/- 0.1% per day for InIII, 0.02 +/- 0.15% per day for YIII, and 0.3 +/- 0.2% per day for CuII labeled immunoconjugates. In the presence of the liver enzyme cathepsin B, an in vitro digestion of 114mIn-labeled conjugate yields a small fragment containing 114mIn. Characterization of the cleavage products shows that this liver enzyme hydrolyzes the peptide linkage before the phenylalanine residue, freeing the In-DOTA triglycine complex from the conjugate. However, the liver enzyme cathepsin D does not cleave the linkage over the span of 7 days. PMID- 8218485 TI - A fluorescent probe and a photoaffinity labeling reagent to study the binding site of maytansine and rhizoxin on tubulin. AB - A fluorescent probe (20-demethoxy-20-[3-[[[5-(dimethylamino)naphthalen-1 yl]sulfonyl] amino]propyl]maytansinol 3-isobutyrate, Dan-PDM-3) and a photoaffinity labeling reagent (20-demethoxy-20-[(p-azidobenzoyl)oxy]maytansinol 3-isobutyrate, DABMI) were prepared by derivatization of ansamitocin P-3 (ASMP 3), a maytansinoid. Dan-PDM-3 consists of a tethered dansyl moiety and a maytansinoid moiety. DABMI contains a p-azidobenzoyl group instead of the tethered dansyl moiety of Dan-PDM-3. These compounds were synthesized by reacting 20-demethoxy-20-hydroxymaytansinol-3 isobutyrate (PDM-3) with the corresponding alkyl halide or benzoic acid. Both inhibit tubulin polymerization as potently as ASMP-3 and compete with ASMP-3 for binding to tubulin. The inhibition constants (Ki) of DABMI for the binding to tubulin of rhizoxin and ASMP-3 were 0.54 and 0.36 microM, respectively, which were nearly equal to the dissociation constant (Kd = 0.43 microM) of DABMI measured by the use of [14C]DABMI. The results suggest that Dan-PDM-3 and DABMI interacted with tubulin at the same site as rhizoxin and maytansine. DABMI is irreversibly bound to tubulin upon irradiation. Dan-PDM-3 and DABMI should be useful probes for studying the binding site. PMID- 8218486 TI - Synthesis of an end-group functionalized polyethylene glycol-lipid conjugate for preparation of polymer-grafted liposomes. AB - Synthesis of a distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) conjugate, bearing a hydrazide group at the unattached end of the polymer chain, was achieved using a new heterobifunctional polymeric reagent. The heterobifunctional PEG derivative carrying on one end a reactive succinimidyl carbonate (SC) group and at the other terminal a tert-butyloxycarbonyl (Boc) protected hydrazide group was prepared by an efficient four step process from readily available PEG-2000. The SC-end group of the polymer reacted readily with the amino group of DSPE forming a stable urethane attachment between lipid and PEG. Acidolytic removal of the Boc group yielded a hydrazide-PEG-lipid conjugate suitable for preparation of polymer-grafted liposomes. Taking advantage of the well-documented chemical versatility of hydrazide groups, various biologically relevant ligands can be linked to this type of functionalized liposomes. PMID- 8218487 TI - Labeling of immunoglobulins with bifunctional, sulfhydryl-selective, and photoreactive coumarins. AB - 4-(Bromomethyl)-6,7-dimethoxy-2-oxo-2H-benzopyran (1a) and 4-(bromomethyl)-7 methoxy-2-oxo-2H-benzopyran (1b) and their iodo analogs (2) reacted selectively with the sulfhydryl groups generated in a limited reduction of the hinge disulfide bonds of an immunoglobulin G (IgG) giving proteins labeled with a fluorescent and/or radioactive moiety. Quantitative alkylation of free thiol groups was obtained with 1 and 125/127I-2. Photodimerization of these adducts produced IgG with covalently joined heavy chains. PMID- 8218489 TI - Biologic and molecular characterization of non-Hodgkin's lymphoma. AB - The wide clinicopathologic heterogeneity of non-Hodgkin's lymphoma is reflected by the various molecular pathways underlying non-Hodgkin's lymphoma pathogenesis, including activation of dominantly acting oncogenes, deletion and inactivation of tumor-suppressor genes, viral infection, deregulation of cytokine networks, and chronic antigenic stimulation. Molecular lesions involving protooncogenes include activation of bcl-2 and bcl-1 in specific subsets of low-grade non-Hodgkin's lymphomas and c-myc in a proportion of intermediate- and high-grade non-Hodgkin's lymphomas. The deregulation of these genes promotes cell growth or protects the tumor population from programmed cell death, or both. Additional genetic abnormalities representing putative sites of novel oncogenes contributing to lymphomagenesis include chromosomal breaks at 3q27 in intermediate-grade non Hodgkin's lymphoma and at 9p13 in small lymphocytic lymphoma. The role of inactivation of tumor-suppressor loci is best exemplified by the frequent inactivation of p53 in Burkitt's lymphoma and by the recurrent deletion of 6q25 q27 and 6q21-q23 in intermediate- and high-grade non-Hodgkin's lymphoma, respectively. Infection by Epstein-Barr virus occurs in a variable fraction of high-grade non-Hodgkin's lymphomas, whereas it is usually absent in other types of non-Hodgkin's lymphoma. Other mechanisms supporting non-Hodgkin's lymphoma growth and development include autocrine or paracrine cytokine loops, or both, and clonal expansion through antigen receptor stimulation. The heterogeneity of non-Hodgkin's lymphoma pathogenesis provides a framework for the development of novel classification methods of potential clinical relevance. PMID- 8218488 TI - Labeling of sulfhydryl groups in intact mammalian cells with coumarins. AB - 4-(Bromomethyl)-6,7-dimethoxy-2-oxo-2H-benzopyran (1) and its 3-[125I]iodo derivative (2) were reacted with sulfhydryl groups of proteins in viable Chinese hamster V79 lung fibroblasts. Pretreatment of cells with dithiothreitol (DTT) as the reducing agent was necessary to give detectable levels of fluorescence. In the absence of DTT, V79 cells incorporated about 1 x 10(-3) pCi/cell of the radioiodinated, no-carrier-added derivative; following incubation of cells with 320 microM DTT the uptake was nearly doubled (1.87 x 10(-3) pCi/cell). PMID- 8218490 TI - Modern treatment approaches for Hodgkin's disease. AB - Recent studies are refining the treatment approaches of radiation therapy and combination chemotherapy in Hodgkin's disease. In early-stage disease, attempts are being made to lessen the toxicity of treatment while maintaining excellent results. Optimal results are achieved in advanced disease with combined radiation therapy and chemotherapy, most often with alternating or hybrid regimens. Several groups have attempted to define a poor-prognosis group of patients with advanced disease who might be candidates for more intensive treatment. PMID- 8218491 TI - Treatment of advanced, aggressive non-Hodgkin's lymphoma. AB - Although advanced, aggressive non-Hodgkin's lymphoma is highly responsive to chemotherapy, only approximately 30% of patients will have long-term disease-free survival and cure. Complex multiple-drug regimens have been claimed to be superior to standard regimens, eg, cyclophosphamide, doxorubicin, vincristine, and prednisone. However, several studies comparing this regimen with various multiple-drug regimens showed equivalent results with a more favorable toxicity profile for the standard regimen. Central nervous system lymphoma continues to carry a grim prognosis, but new approaches combining chemotherapy with radiation may lead to improved treatment. The availability of hematopoietic growth factors may help determine the role of dose intensity in the treatment of advanced, aggressive non-Hodgkin's lymphoma. PMID- 8218492 TI - Second neoplasms following treatment of Hodgkin's disease. AB - In the past several decades, malignant lymphomas have been transformed from almost uniformly fatal illnesses to diseases that can be treated, with an expectation of long-term remission in a majority of patients. However, with the recognition of treatment efficacy also has come an appreciation of long-term sequelae. Among these late effects, the induction of a second cancer represents one of the most feared complications. For many years, acute nonlymphocytic leukemia has been the most frequently reported secondary malignancy; however, with increasing length of follow-up, solid tumors have replaced leukemia as the most commonly observed second cancers. The risk of second neoplasms depends on some treatment associations and on certain host-related factors. Less toxic treatment strategies need to be designed and appropriately tested in comparative trials. However, it is necessary to stress that, without effective therapy, the natural outcome of malignant lymphomas is death from progressive disease. PMID- 8218493 TI - Cancer in AIDS. PMID- 8218494 TI - The epidemiology of AIDS-related malignancies. AB - Immunosuppression resulting from HIV infection does not explain the unique distribution of Kaposi's sarcoma across risk groups. A majority of cases occur among homosexual men, particularly those with oral-anal contact, those with sexual contacts in high-risk cities, and those frequently use nitrite inhalants, suggesting a currently unidentified etiologic cofactor. Risk of non-Hodgkin's lymphoma among HIV-infected persons continues to increase over time. Because all HIV-infected groups are at high risk of non-Hodgkin's lymphoma, environmental cofactors may be less important in the disease's etiology. Because data on risk factors for AIDS-related non-Hodgkin's lymphoma are limited, further studies are needed. Cohort studies suggested that the risk of Hodgkin's disease is greater among HIV-infected persons; however, the number of cases reported has been small. Hodgkin's disease occurring among HIV-infected persons is more aggressive than and differs in presentation from that among noninfected persons. The addition of invasive cervical cancer to the US Centers for Disease Control definition of AIDS is based on data showing that HIV-infected women have a high prevalence of cervical disease. Although no conclusions can yet be drawn regarding the temporal relationship of cervical disease and HIV infection, there is evidence of a direct relationship between the degree of HIV-induced immunosuppression and the extent of cervical disease. Other cancers are being diagnosed among AIDS patients, and monitoring of the risk of solid tumors among various cohorts of high-risk and HIV infected persons continues. PMID- 8218495 TI - AIDS-associated Kaposi's sarcoma pathogenesis, clinical features, and treatment. AB - Kaposi's sarcoma is the most common tumor associated with HIV-1 infection. Kaposi's sarcoma is seen most frequently among homosexual or bisexual men, the reasons for which are unknown. Culture of Kaposi's sarcoma spindle cells has been very useful to study various biologic features of the tumor and to develop novel drug therapy. Treatment of AIDS-associated Kaposi's sarcoma is planned based on tumor burden, immunologic status of the patient, and bone marrow rescue. All treatment types at present only provide palliation, whereas efforts to find more effective therapy and possibly preventive therapy are in progress. PMID- 8218496 TI - Clinical aspects of AIDS-related Kaposi's sarcoma. AB - Kaposi's sarcoma was one of the first conditions defining the new disease AIDS in 1981. From the outset, it was quite apparent that the biology of Kaposi's sarcoma in the setting of AIDS was quite different from that of most other known neoplasms. This observation led many investigators to speculate that Kaposi's sarcoma is, in fact, a reactive tumor and not a true malignancy. Our understanding of the pathogenesis of Kaposi's sarcoma has evolved over the years, and it now believed that the tumor arises from mesenchymal cells, which are influenced by HIV, various cytokines or growth factors, and perhaps other viruses or environmental factors operating in the setting of immune suppression. The tumor itself has various clinical manifestations, ranging from indolent cutaneous tumors to rapidly growing tumors involving lung and other viscera. New approaches to the treatment of Kaposi's sarcoma include inhibition of angiogenic and Kaposi's sarcoma stimulating growth factors, eg, interleukin-6, fibroblast growth factor, tumor necrosis factor, oncostatin-M, and the HIV-tat gene product. Additionally, improvement in our use of cytotoxic chemotherapy, interferons, and antiretroviral drugs has led to better management of complications of the tumor and of HIV itself. This review highlights recent advances in our understanding of Kaposi's sarcoma and its treatment, with a focus on pathogenesis and novel therapies. PMID- 8218497 TI - Biologic aspects of AIDS-associated non-Hodgkin's lymphoma. AB - Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas represent a significant and formidable clinical problem. They also represent an important biologic model for investigating the development and progression of high-grade malignant lymphomas and for studying lymphomas that develop in the setting of immune deficiency. A vast majority of non-Hodgkin's lymphomas exhibit clonal immunoglobulin gene rearrangements and, hence, are B-cell neoplasms. Most express B-cell phenotypes, but a minority, predominantly body cavity-based tumors, express indeterminate phenotypes. AIDS-associated non-Hodgkin's lymphomas do not contain HIV. However, approximately 40% of systemic non-Hodgkin's lymphomas, predominantly those with immunoblastic plasmacytoid morphology, and essentially 100% of primary central nervous system AIDS-associated non-Hodgkin's lymphomas contain Epstein-Barr virus. The c-myc protooncogene is rearranged in approximately 80% of systemic cases, predominantly in those with Burkitt's and Burkitt's-like morphology. Point mutations of the ras gene are detectable in approximately 15% of systemic cases. The p53 tumor-suppressor gene is mutated in approximately two thirds of systemic AIDS-associated Burkitt's and Burkitt's-like non-Hodgkin's lymphomas. The retinoblastoma tumor-suppressor gene does not appear to be mutated or deleted in AIDS-associated non-Hodgkin's lymphomas. In summary, various genetic lesions occur in AIDS-associated non-Hodgkin's lymphomas, which appear to vary according to the anatomic site of disease (systemic vs central nervous system vs body cavity) and the histopathology (Burkitt's vs immunoblastic vs large cell). Further active investigation is necessary to determine the role of these and possibly other genetic lesions in AIDS lymphomagenesis. PMID- 8218498 TI - Clinical aspects of HIV-related lymphoma. AB - The number of cases HIV-associated non-Hodgkin's lymphoma continues to increase as the AIDS epidemic grows. Approximately 3% of AIDS-defining illnesses are non Hodgkin's lymphoma. The number of non-Hodgkin's lymphoma cases may actually be higher because many cases go unreported. There is also evidence that increasing numbers of patients who are surviving longer on antiretroviral therapy are developing non-Hodgkin's lymphoma. A majority of HIV-related lymphomas are large cell, either high-grade immunoblastic or aggressive intermediate grade, diffuse cleaved, or small noncleaved (Burkitt's-like). HIV-related non-Hodgkin's lymphomas behave aggressively. They are predominantly extranodal and often show unusual patterns of organ involvement. They are typically stage III or IV at the time of diagnosis. Current treatment strategies involve the use of combination chemotherapy regimens with or without antiretroviral therapy. Current studies are evaluating the efficacy of low-dose chemotherapy regimens versus standard-dose regimens with granulocyte-macrophage colony-stimulating factor support. New strategies for treating AIDS-associated non-Hodgkin's lymphoma will incorporate our current knowledge of AIDS-related lymphoma pathogenesis. Factors that reflect a patient's state of immunodeficiency seem to be the most important prognostic features determining clinical outcome after treatment. Patients with good prognostic features may benefit the most from aggressive treatment regimens. AIDS related primary central nervous system lymphomas continue to comprise approximately 15% of AIDS-related non-Hodgkin's lymphoma cases. Treatment is limited. Although whole-brain radiation therapy can result in an improved neurologic status, the median survival remains 3 to 4 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218499 TI - Anogenital neoplasia in patients with HIV infection. AB - Individuals infected with HIV have been noted to have an increased rate of anogenital neoplasia. Recent studies have attempted to demonstrate the extent of anal and cervical cancer in the HIV-infected population as well as describe the role of human papillomavirus coinfection in the pathogenesis of these malignancies. This paper reviews the current literature pertaining to HIV-related anogenital neoplasia and suggests a schema for the clinical management of patients at risk. PMID- 8218500 TI - Etiology, epidemiology, risk and prognostic factors, screening, and imaging of gynecologic cancers. AB - This review presents some of the articles published over the past year pertaining to the etiology, epidemiology, risk and prognostic factors, screening, and imaging techniques of gynecologic cancer. The most significant advances in this period were made in the area of the genetics of gynecologic cancers and the factors that control tumor growth. New technologies are being developed in this area, which may eventually produce therapies aimed at controlling gynecologic cancers at the genetic or cellular level. Research continues for ideal screening tests for noncervical gynecologic cancers. Continuing advances were made in imaging techniques, eg, magnetic resonance imaging, which can now display very high-resolution pictures of cancers in vivo, but this technology is limited by both cost and insufficient studies proving its value. PMID- 8218501 TI - Surgery for gynecologic malignancies. AB - There is almost universal acceptance of the importance of cytoreductive surgery in advanced ovarian cancer. However, recent studies argued against attempts to remove every last vestige of tumor in patients with many large tumor masses in the upper abdomen. Successful secondary cytoreduction at second surgery may improve survival in some selected patients. The change from a clinical to a surgical staging for endometrial neoplasia undoubtedly improved the accuracy of staging, but it remains to be seen if appropriate clinical treatment of high-risk patients improves survival. Large loop excision of the transformation zone has become increasingly popular for treating cervical intraepithelial neoplasia. Lesions with no more than a 3-mm depth of invasion and with no vascular space involvement may be treated by simple hysterectomy. The morbidity and postoperative mortality with treatment of invasive squamous carcinoma of the vulva have been reduced by modifying the extent of vulvar and groin dissection. Recent studies suggested that the femoral nodes should be removed when performing inguinal lymphadenectomy. Laparoscopic pelvic and para-aortic lymphadenectomies and even laparoscopically assisted radical hysterectomies have been reported in patients with gynecologic malignancies. It remains to be seen what place laparoscopy will come to occupy in the armamentarium of the gynecologic oncologist. PMID- 8218502 TI - Radiotherapy for gynecologic cancer. AB - The past year has not seen any breakthroughs in radiation treatment of gynecologic cancer. In reference to cervix cancer, important contributions concerning side effects and the role of radiosensitizers were published. The lack of randomized trials dealing with adjuvant radiotherapy is obvious. Improvement based on technical progress can be expected. For ovarian cancer, an important review about whole abdominal irradiation as adjuvant therapy was published. The long-term complication rate of whole abdominal irradiation is acceptable, but whether adjuvant whole abdominal irradiation has an effect upon survival superior to that of chemotherapy is still discussed. Combined treatment with chemotherapy and radiation therapy for advanced ovarian cancer is feasible, but there is no proof that the addition of radiotherapy improves survival. Literature about endometrial cancer was scarce in 1992 and did not contribute to the major question: Does adjuvant radiotherapy have any effect in endometrial cancer? PMID- 8218504 TI - Lymphoma. PMID- 8218503 TI - The biology of ovarian cancer. AB - Recent studies have begun to elucidate the molecular events involved in the development of ovarian cancer. First, it has been shown that epithelial ovarian cells both produce and have receptors for many peptide growth factors. It is possible that these growth factors may participate in autocrine and paracrine growth-regulatory pathways in these cells. Increased activity of stimulatory factors, eg, transforming growth factor-alpha, or decreased activity of inhibitor factors, eg, transforming growth factor-beta, may facilitate malignant transformation. In addition, it has been shown that ovarian cancer cells often have acquired the ability to degrade extracellular matrix and invade the underlying tissues. Finally, alterations in several oncogenes and tumor suppressor genes, including HER2/neu, c-myc, and p53, have been found in ovarian cancers. Although exciting insights into the molecular pathology of ovarian cancer have been gained, we remain far from a comprehensive understanding of the biology of this highly lethal disease. PMID- 8218505 TI - Cancer in AIDS. PMID- 8218506 TI - Gynecologic cancer. PMID- 8218507 TI - Relaxation training as a treatment for irritable bowel syndrome. AB - Although there have been many successful, controlled demonstrations of the clinical efficacy of multicomponent treatments for irritable bowel syndrome (IBS), in the present study we sought to evaluate a single component of many of these regimens, relaxation training. Eight IBS patients received a 10-session (over 8 weeks) regimen of abbreviated progressive muscle relaxation with regular home practice while 8 comparable patients merely monitored GI symptoms. Based on daily GI symptom diaries collected for 4 weeks before and 4 weeks after treatment (or continued symptom monitoring), the Relaxation condition showed significantly (p = .05) more improvement on a composite measure of primary GI symptom reduction than the Symptom Monitoring condition. Fifty percent of the Relaxation group were clinically improved at the end of treatment. PMID- 8218508 TI - Symptom prescription: inducing anxiety by 70% exhalation. AB - This study investigates the effects of partial exhalation to feelings of anxiety. Thirty five volunteer subjects (14 male, 21 female, mean age 40.6) were first trained in slow diaphragmatic breathing (SDB). Then subjects rated their anxiety levels on a scale from 1 (none) to 5 (extreme) in sequential conditions of SDB, 70% subjective exhalation, and SDB. During the 70% subjective exhalation phase, subjects were instructed to breathe and limit their exhalation to 70% of the inhaled volume during each consecutive breath. The 70% subjective condition significantly (P < .0005) increased subjects' anxiety levels as compared to the initial SDB baseline, while a return to SDB significantly reduced the anxiety levels. The 70% approach appears useful in demonstrating to the client that possible changes in breathing patterns can affect anxiety. PMID- 8218509 TI - Abstracts of papers presented at the 24th annual meeting of the Association for Applied Psychophysiology and Biofeedback. Los Angeles, California, March 25-30, 1993. PMID- 8218510 TI - Concurrent partnerships could cause AIDS epidemics. AB - There is a need for new hypotheses to supplement existing explanations for the observed differences in HIV prevalence between countries and within countries. Due to high levels of viraemia during the initial phase of HIV infection, networks of concurrent regular partnerships in a community could be the determining factor in the development of an AIDS epidemic. If this hypothesis is true, projections of the future development of the epidemic could be altered. Simple health education messages based on the hypothesis might make a major contribution to the prevention and control of AIDS epidemics. PMID- 8218511 TI - Clinical management of HIV disease in intravenous drug-users. AB - Intravenous drug-users comprise a major group of HIV-infected individuals in the developed world and, whilst progression of HIV disease in them appears little different from other risk groups, their medical presentations may be altered by continuing drug use. Drug-users are particularly susceptible to bacterial infections irrespective of their HIV status; they may present with symptoms directly caused by their drugs, which can be difficult to differentiate from non drug-related causes and may closely resemble symptoms directly attributable to HIV. In addition, the life style associated with drug use can make compliance difficult, but in clinics combining HIV care and methadone prescribing these problems can be overcome. PMID- 8218512 TI - Pharmacological treatment of acute vulvovaginal candidiasis. PMID- 8218513 TI - Assessing statistics for the measurement of workload at a genitourinary medicine clinic. AB - Since January 1985 James Pringle House, the genitourinary medicine (GUM) clinic at London's Middlesex Hospital, has built up an extensive computerized patient database. Yearly statistics relating to 1) individual patients, 2) diagnoses, 3) attendances, and 4) an activity estimator (combining features of attendances and their corresponding diagnoses) are extracted. Each is assessed as a potential tool for quantifying the rising workload associated with the clinic's increased staffing levels and expanded services. Only the activity estimator identifies an upward trend, rising 26.3% from 1985-86 to 1991-92, caused largely by human immunodeficiency virus (HIV) and hepatitis B related attendances. This activity estimator could provide the basis for a workload reporting facility on all GUM computer systems. The 4 statistics exhibit other useful information, including a 21.0% rate of non-attendance (a substantial hidden addition to workload) and a strong allegiance to the clinic from patients residing outside of the local Health Authority region. PMID- 8218514 TI - Anogenital warts in prepubertal children; sexual abuse or not? AB - Forty-two prepubertal children presenting with anogenital (AG) warts (15 boys and 27 girls) were prospectively followed up (mean 15.9 months, SD 12.24). Most (73.8%) of these children had perianal condylomatous-type warts and 11 (26.2%) had concurrent non-genital (NG) warts. None had any other AG infections or sexually transmitted disease (STD). Twelve (28.6%) children acquired their AG warts by vertical transmission from an infected maternal birth canal, 3 (7.1%) by autoinoculation from common hand warts and 2 children (4.8%) through sexual abuse. In the remaining 25 children (59.5%) mode of acquisition of AG warts was uncertain but not thought to be sexual. Human papilloma virus (HPV) DNA (types 6/11, 16/18 or 31,33,35-31+) was detected in 10/32 (31.3%) of AG warts biopsied from these children, types 6/11 in the majority of positive biopsies (9/10). Detection of HPV DNA (types 6/11, 16/18 or 31+) in a child's AG warts was significantly associated with either vertical or sexual transmission (P < 0.02). Thirty-one children had their warts treated with a combination of scissor excision and electrocautery under general anaesthesia. Warts recurred in 10 (31.4%) of these children all within 4 months following treatment. Spontaneous resolution of AG warts was seen in 9 (21.4%) children. Of 42 children with AG warts 10 (23.8%) had at least one adult family member with AG warts, 13 (36.9%) on adult family member with another AG infection or STD, and 23 (62.2%) had a mother with cervical intraepithelial neoplasia (CIN). Twenty (47.6%) of these children had a family member with NG warts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218515 TI - A unique community of family-oriented prostitutes in Nepal uninfected by HIV-1. AB - In the Mid Western and Far Western regions of Nepal live a unique group of prostitutes which maintains strong bonds resulting from 'untouchable' caste status and family tradition. Known as the Badis (pronounced 'bod ee'), it is estimated that well over 5000 Badi prostitutes are now actively engaged in the sex trade in Nepal. In 1991, a study of some of the social and cultural practices of this unique group was completed. In addition to the provision of counselling and information about STDs and AIDS, over 300 prostitutes were interviewed about their sex practices within the Badi community. Two hundred and twenty-eight Badi prostitutes consented to voluntary confidential testing for VDRL, and 250 consented to anonymous, unlinked serosurveillance for HIV-1. As previous studies have shown moderate to high rates of HIV-1 infection among prostitutes in general, and even higher rates of infection in low class prostitutes, some prevalence of VDRL as well as HIV-1 was expected. However, of the 228 Badi prostitutes tested, 154 (70%) were found to be VDRL positive, while none were found positive for HIV-1. At the same time, many of these prostitutes reported a history of constant and often untreated STDs. The implications for the future prevention of HIV infection in this group are obvious and striking. With immediate and effective STD treatment as well as counselling, the Badis represent one high risk group in which the global AIDS epidemic could be drastically reduced, or even averted. PMID- 8218516 TI - Endemic versus non-endemic gonorrhoea in Stockholm: results of contact tracing. AB - The aim of the present study was to characterize endemic versus non-endemic gonorrhoea to identify risk groups for transmission and to evaluate the effects of intensified contact tracing performed by specially trained social workers at venereal clinics. A total of 671 gonorrhoea patients (283 women and 388 men) comprised the study group. Seventy percent of the women and 48% of the men had an endemic infection (P < 0.001). Men without a steady partner had an increased risk of non-endemic infection. A decrease from 75% to 40% was noted in the proportion of endemic infection in Stockholm from the first quarter of the study period (2 years) to the last. Contact tracing resulted in 1.2 identified partners per patient. A total of 736 partners were examined either as a result of contact tracing efforts or because they had sought medical care on their own prior to intervention. Forty-seven percent of these partners were infected, 44% were not infected and 9% were examined outside the study with results unknown to us. The partner notification efforts yielded 161 new untreated cases. Contact tracing of women generated one new case per 4.0 interviewed women and contact tracing of men one new case per 4.3 interviewed men. Interviewing index patients with endemic infection yielded the highest number of new cases. Forty-three percent of the patients were infected outside Stockholm but only a smaller part of these patients spread their infection further into the community.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218517 TI - Ondansetron usage in HIV positive patients: a pilot study on the control of nausea and vomiting in patients on high dose co-trimoxazole for Pneumocystis carinii pneumonia. AB - This was an open, single centre study, to evaluate the safety and efficacy of ondansetron in the treatment of co-trimoxazole associated nausea and vomiting in AIDS patients. Sixteen patients presenting with their first episode of HIV associated Pneumocystis carinii pneumonia (PCP) on high dose co-trimoxazole were given ondansetron 8 mg orally, every 8 h. Measurements were made from data recorded by each patient on diary cards. In this study 11 out of 16 (69%) patients on ondansetron experienced good control of emesis (2 or less emetic episodes) on their 'worst day' of therapy and 8 out of 16 (50%) of patients demonstrated good control of emesis throughout their treatment with co trimoxazole. Good control of nausea (mild or none) was achieved in 7 out of 16 (47%) patients. A total of 7 patients were able to complete the full course of co trimoxazole whilst on ondansetron. One serious adverse event (Stevens-Johnson syndrome) was reported and felt to be unrelated to ondansetron. If conventional anti-emetics fail to achieve control of symptoms or have unacceptable side effects, ondansetron may represent a possible alternative. PMID- 8218518 TI - A study comparing cervical cytology results from a genitourinary medicine department with those of two other local populations. AB - A retrospective study compared one year's cervical smear results from 4920 women from the following 3 populations in Leicestershire; the Genitourinary Medicine (GUM) Departments; the city family planning clinic (FPC); and a general practice (GP) in a local University town. The results were standardized for age by logistic regression. Cytological abnormality was divided into: dyskaryosis (all grades), borderline, and inflammatory changes. The GUM attenders had an excess of total cervical smear abnormalities compared to both the FPC (P < 0.001) and GP population (P < 0.001) after adjusting for age. The FPC and GP rates of smear abnormality were similar at 60 and 63 per 1000 women screened, respectively, while the rate for the GUM clinic was 155 per 1000 women screened. PMID- 8218519 TI - Anti-bovine viral diarrhoea virus antibodies in adult Zambian patients infected with the human immunodeficiency virus. AB - Bovine viral diarrhoea (BVD) virus is a cosmopolitan pestivirus of animals which is associated with diarrhoea, immunosuppression and synergy with other pathogens. This study was conducted to establish the prevalence of anti-BVD virus antibodies in healthy Zambian adults and those with asymptomatic and symptomatic HIV disease. Sera from 1159 adults were tested for anti-BVD virus antibodies using the indirect immunofluorescence test and the confirmatory Western blot. Of the 1159 sera examined, 180 (15.5%) showed significantly elevated titres of anti-BVD antibodies. These included 70 out of 477 (14.7%) HIV-negative healthy adults; 73 out of 480 (15.2%) of HIV-positive asymptomatic individuals; 23 out of 129 (17.8%) HIV-seropositive patients with associated illnesses excluding diarrhoea; and 14 out of 73 (19.2%) of HIV-seropositive patients with chronic diarrhoea. HIV seropositive patients with chronic diarrhoea or associated illnesses appear to have significantly increased seroprevalence of anti-BVD virus antibodies (P = > 0.01). The mechanism of interaction between BVD virus and HIV infections and the synergistic effects with other opportunistic pathogens in humans requires definition. PMID- 8218520 TI - AIDS presenting as fever of undetermined origin: report of four cases. PMID- 8218521 TI - Prevalence of uro-genital Chlamydia trachomatis infection in El Salvador. Men with urethritis and healthy medical students. PMID- 8218522 TI - Development and validation of a high-performance liquid chromatographic method for the quantitation of warfarin enantiomers in human plasma. AB - An HPLC method for the quantitation of warfarin enantiomers in human plasma has been developed and validated. Baseline separation of S- and R-warfarin was achieved on a silica-bonded beta-cyclodextrin column with a mobile phase of acetonitrile-acetic acid-triethylamine (1000:3:2.5, v/v/v). The detection was performed at 320 nm. The established linearity range was 12.5-2500 ng ml-1 (r > 0.99). The limit of quantitation was 12.5 ng ml-1 for each enantiomer. Inter-day precision and accuracy of 12.5 ng ml-1 standards were 12.1% relative standard deviation (RSD) and +0.67% bias for S-warfarin and 9.7% RSD and +10.8% bias for R warfarin. The low quality control samples at 37.5 ng ml-1 showed 6.9% RSD and 0.0% bias for S-warfarin, 7.2% RSD and +0.5% bias for R-warfarin. S-Naproxen was used as internal standard. Potential metabolites of warfarin were well resolved from S- and R-warfarin, the internal standard (S-naproxen) and each other. The run time was 25 min. The silica-bonded beta-cyclodextrin column showed excellent stability; over 1000 samples were injected without significant loss of performance. The column variability test showed that the method can be applied on several batches of beta-cyclodextrin columns but not all the beta-cyclodextrin columns were suitable for this method. PMID- 8218523 TI - A liquid chromatographic method for the determination of the enantiomeric purity of the anticancer drug, 9-amino-20(S)-camptothecin. AB - A method was developed for determining the enantiomeric purity of 9-amino-20(S) camptothecin (9-A-20(S)-CAM). The chiral derivatizing reagent, 1-(1 naphthyl)ethyl isocyanate (NEI) was used to derivatize the enantiomers of 9-A CAM, and 1H-NMR, LC-MS, and LC-UV were used to identify and quantitate the two diastereomers produced. During the first 24 h, derivatization was exclusively at the 9-amino nitrogen. The much slower reaction involving reaction of NEI with the 20-hydroxy oxygen could be prevented by quenching the reaction within the first 24 h with methanol. NMR analysis provided useful information about the site of derivatization; however, the partial separation of the signals was insufficient for quantitative analysis of the two diastereomers. Whereas baseline resolution of the two diastereomers was achieved by reversed-phase LC, the reproducibilities of the resolution and the peak area ratios were dependent on the nature and composition of the mobile phase, the flow rate, the column temperature, sample concentration and sample preparation. PMID- 8218524 TI - Determination of guaifenesin in human plasma by liquid chromatography in the presence of pseudoephedrine. AB - A sensitive and specific liquid chromatography (LC) procedure was developed and validated for the determination of guaifenesin in human plasma in the presence of pseudoephedrine. Guaifenesin was extracted from plasma at pH 6.9-7.1 using methanol-methylene chloride (5:95, v/v) containing the internal standard mephenesin and pseudoephedrine. The organic layer was separated and evaporated to dryness and the residue reconstituted with the mobile phase containing methanol acetonitrile-phosphate buffer (0.05 M) (11:11:78, v/v/v) containing 4 mM heptane sulphonic acid and 1% glacial acetic acid. The separation was performed on a mu Bondapak C18 column. The flow rate was 1.0 ml min-1. The retention times for guaifenesin and mephenesin were 7.9 and 15.7 min, respectively. Linearity of response was observed in the concentration ranges of 50-1000 ng ml-1 and 1-4 micrograms ml-1. Accuracy was within 15.4% of the true value for the inter-day and intra-day analysis. The precision, as measured by the RSD, ranged from 4.8 to 8.7% for intra-day. The reproducibility of inter-day ranged from 5.0 to 8.4%. The per cent recovery from plasma ranged from 88.6 to 97.6. Data are presented to illustrate the practicality of the method for the evaluation of guaifenesin plasma levels in the presence of pseudoephedrine after multiple oral administration of two sustained release tablets containing 600 mg of guaifenesin per tablet to six male healthy volunteers. The mean half-life of guaifenesin in human subjects was found to be 2.88 h and ranged from 1.36 to 5.25 h. PMID- 8218525 TI - Determination of mirfentanil hydrochloride (A-3508.HCl) in human plasma by liquid chromatography-mass spectrometry. AB - A method for the quantitation of mirfentanil hydrochloride (A-3508.HCl) in human plasma is presented for the first time, using LC-MS with single ion monitoring. The drug is extracted with a C-18 solid-phase cartridge and the extract is analysed using a 3 cm C-18 column connected to the ion source of a mass spectrometer via a thermospray interface. The intense ion produced by the protonated molecular ion at m/z 377 is detected by the mass spectrometer in positive-ion mode. The range of quantitation is 0.4-100 ng ml-1 from a 0.5 ml plasma sample. Results of assay validation are given. The method was used to analyse samples from a human pharmacokinetic study following intravenous administration of mirfentanil hydrochloride. PMID- 8218526 TI - Determination of the kinetics of degradation of 13-cis-retinoic acid and all trans-retinoic acid in solution. AB - The degradations of 13-cis-retinoic acid and all-trans-retinoic acid in an organic solvent were determined with an HPLC assay. The degradation curves at 70, 50 and 37 degrees C all showed autocatalytic characteristics for both isomers. For this kind of complex reaction, the usual method cannot be used to estimate the shelf-lives and half-lives at room temperature. In this work a new method was developed to directly calculate the shelf-lives and half-lives. From this equation the activation energy was found to change as the multiple step reaction progressed. PMID- 8218527 TI - HPLC analysis of salinomycin in human plasma using pre-column oxidation and automated heart cut column switching. AB - Salinomycin is a polyether antibiotic used to promote growth in cattle and poultry. Workers may be exposed to salinomycin through handling of animal feeds that contain the drug and it is necessary to monitor plasma samples from these workers for salinomycin to ensure safety. A method for analysis of salinomycin in plasma samples was therefore developed. Salinomycin and the internal standard narasin are extracted into iso-octane then subjected to silica gel solid-phase extraction in which the sample is washed with methylene chloride-methanol (98.5:15) then eluted with a 90:10 proportion of the same mixture. Both salinomycin and narasin are oxidized with pyridinium dichromate to form a chromophore absorbing at 225 nm. The concentrated product was injected onto a C18 pre-column and heart cut from 1.85 to 3.65 min onto a C18 analytical column. The method was shown to be selective for salinomycin and narasin in six blank plasma samples. The method was linear over a range of 15-300 ng ml-1 with a detection limit of approximately 5 ng ml-1. The mean absolute recovery was found to be 93.4 and 97.9% for salinomycin and narasin, respectively. The method was accurate to within 5% at all concentrations studied. Within-run and between-run precision were both less than 8% RSD at all concentrations studied and the method was suitable for the purpose of monitoring plasma from exposed agricultural workers. PMID- 8218528 TI - Separation of 13-cis and all-trans retinoic acid and their photodegradation products using capillary zone electrophoresis and micellar electrokinetic chromatography (MEC). AB - Two retinoic acid isomers; 13-cis retinoic acid and all-trans retinoic acid and their photodegradation products were resolved with capillary electrophoresis (CE) (UV detector, 345 nm) using three different mobile phases: method 1--an acetonitrile modified borate buffer (pH 8.5); method 2--borate buffer (pH 8.5) modified with acetonitrile and alpha-cyclodextrin; and method 3--borate buffer (pH 8.5) modified with SDS (MEC). Concentration of acetonitrile in the buffer was varied from 10 to 50% in method 1 and resolutions of 0-1.9 were obtained for the two retinoic acid isomers. Similarly in method 2, concentration of alpha cyclodextrin in the buffer (with 10% acetonitrile) was varied from 0 to 40 mM, giving resolutions of 0-3.8. In method 3, concentration of SDS in the buffer was varied from 5 to 60 mM resulting in resolutions of 1.3-4.1. Optimum separation conditions for the three methods were applied to the separation of photodegradation products of the two retinoids after exposure to fluorescent light for 36 h. A buffer modified with 45% acetonitrile and the same buffer modified with 10 mM SDS gave incompletely resolved electropherograms with a 72 cm x 50 microns capillary (50 cm to the detector). A buffer containing 20 mM alpha cyclodextrin 10% acetonitrile gave completely resolved peaks for each isomer. The buffer containing 10 mM SDS gave completely resolved peaks for the photodegradation products when a 122 cm x 50 microns capillary (100 cm to detector) was used. PMID- 8218529 TI - Charge-transfer complexes of iodine and nonionic surfactants: interpretation and use in the Winkler method. AB - Formation constants (Kc) and molar absorption coefficients (epsilon c) of complexes of iodine and various nonionic surfactants were determined, providing a basis for selection of a surfactant for use in a spectrophotometric modification of the Winkler method. The method of calculation of Kc and epsilon c was extended to include absorption by triiodide at the wavelength of maximum absorbance of the complex. Because the molar absorption coefficients of polyoxyethylene 10 oleyl ether (oleth 10) and polyoxyethylene 23 oleyl ether were significantly greater than those of other surfactants, they are superior candidates for use in the Winkler method. Formation constants could not be correlated with molecular characteristics of the surfactants such as alkyl chain or polyoxyethylene chain length, nor with physical characteristics of iodine-surfactant solutions such as reduction of iodine loss due to volatilization. PMID- 8218530 TI - Estimating shelf-life using L1 regression methods. AB - The shelf-life of a drug is usually determined by fitting the assayed values of drug potency versus time to a linear least-squares model. In least-squares models, the parameters are estimated by minimizing the sum of squares of the residuals. Shelf-life is estimated as the time corresponding to the intersection point of the fitted line and the minimum acceptable per cent or proportion of the initial drug potency. The least-squares method can be seriously affected by outliers, leading to erroneous shelf-life estimates. In this paper, an alternative method, based on minimizing the sum of absolute deviations, was applied to the shelf-life determination problem. The resistance of these L1 based estimates to outliers was demonstrated using a typical stability dataset. PMID- 8218531 TI - A liquid chromatographic method for the determination of tolnaftate in pharmaceutical formulations. AB - A simple LC method was developed and validated for the analysis of tolnaftate in various pharmaceutical formulations. This method did not require any complex sample extraction procedure. The chromatographic separation was achieved on a reversed-phase, C18 column with UV detection at 258 nm. This isocratic system was operated at ambient temperature and required 9 min of chromatographic time. The mobile phase consisted of methanol-aqueous potassium dihydrogen phosphate solution (80:20, v/v) at a flow rate of 1.5 ml min-1. Standard curves were linear over the concentration range of 1.0-51.0 micrograms ml-1. Within-day and between day relative standard deviation values ranged from 0.7 to 2.9% and from 1.3 to 3.4%, respectively. This method was used to quantify tolnaftate in microcapsule, microsphere, cream, powder, liquid, liquid aerosol and powder aerosol formulations. This method was also used to study the stability of tolnaftate in solution during its extraction from microcapsule formulations. PMID- 8218532 TI - Determination of chlorpheniramine maleate in tablets and injections by 1H-NMR spectroscopy. PMID- 8218533 TI - Stochastic model neuron without resetting of dendritic potential: application to the olfactory system. AB - A two-dimensional neuronal model, in which the membrane potential of the dendrite evolves independently from that at the trigger zone of the axon, is proposed and studied. In classical one-dimensional neuronal models the dendritic and axonal potentials cannot be distinguished, and thus they are reset to resting level after firing of an action potential, whereas in the present model the dendritic potential is not reset. The trigger zone is modelled by a simplified leaky integrator (RC circuit) and the dendritic compartment can be described by any of the classical one-dimensional neuronal models. The new model simulates observed features of the firing dynamics which are not displayed by classical models, namely positive correlation between interspike intervals and endogenous bursting. It gives a more natural account of features already accounted for in previous models, such as the absence of an upper limit for the coefficient of variation of intervals (i.e. irregular firing). It allows the first- and second-order neurons of the olfactory system to be described with the same basic assumptions, which was not the case in one-point models. Nevertheless it keeps the main qualitative properties found previously, such as the existence of three regimens of firing with increasing stimulus concentration and the sigmoid shape of the firing frequency of first-order neurons as a function of the logarithm of stimulus concentration. PMID- 8218534 TI - Influence of the mechanical properties of a manipulandum on human operator dynamics. II. Viscosity. AB - The influence of the viscosity of a manipulandum used by a human operator in a position-control pursuit-tracking task was examined. An active servo-system was used to set the viscosity of a manipulandum (motor) connected to the forearm to one of seven levels ranging in a geometric series from 12 to 800 N.s/m. During each condition the viscosity of the motor was held constant by a computer while subjects tracked, by moving their forearm in the sagittal plane, a visually presented target whose position changed randomly every 1.5 s for 255 s. Nonparametric and parametric impulse response functions were calculated between the input (target) and output (position) in each tracking condition. Nonparametric analyses revealed that subjects became sluggish at higher viscosities (above 200 N.s/m) and took longer to reach the target. A second-order low-pass transfer function was found to provide a very good description of tracking performance at each viscous level. The gain and damping parameter of this transfer function were not affected by the manipulandum's viscosity, whereas both the pure delay and natural frequency of the human operator system decreased systematically with increasing manipulandum viscosity. These findings suggest that over the range of viscosities studied, there is no speed-accuracy trade-off in terms of determining an optimal level of manipulandum viscosity for a human operator, and that a less viscous interface will result in faster performance. PMID- 8218535 TI - Reconstructing muscle activation during normal walking: a comparison of symbolic and connectionist machine learning techniques. AB - One symbolic (rule-based inductive learning) and one connectionist (neural network) machine learning technique were used to reconstruct muscle activation patterns from kinematic data measured during normal human walking at several speeds. The activation patterns (or desired outputs) consisted of surface electromyographic (EMG) signals from the semitendinosus and vastus medialis muscles. The inputs consisted of flexion and extension angles measured at the hip and knee of the ipsilateral leg, their first and second derivatives, and bilateral foot contact information. The training set consisted of data from six trials, at two different speeds. The testing set consisted of data from two additional trials (one at each speed), which were not in the training set. It was possible to reconstruct the muscular activation at both speeds using both techniques. Timing of the reconstructed signals was accurate. The integrated value of the activation bursts was less accurate. The neural network gave a continuous output, whereas the rule-based inductive learning rule tree gave a quantised activation level. The advantage of rule-based inductive learning was that the rules used were both explicit and comprehensible, whilst the rules used by the neural network were implicit within its structure and not easily comprehended. The neural network was able to reconstruct the activation patterns of both muscles from one network, whereas two separate rule sets were needed for the rule-based technique. It is concluded that machine learning techniques, in comparison to explicit inverse muscular skeletal models, show good promise in modelling nearly cyclic movements such as locomotion at varying walking speeds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218536 TI - Factors associated with transfusion requirements during treatment for acute myelogenous leukemia. AB - Supportive care is a prerequisite for intensive chemotherapy in leukemic patients. Little has been published about quantitative aspects of red blood cell and platelet transfusions. We evaluated transfusion requirements and factors associated with observed differences in 206 patients undergoing initial induction consolidation chemotherapy for newly diagnosed acute myelogenous leukemia. All patients were treated during a 5-year period in 12 hospitals on a common protocol of the Swiss Study Group for Clinical Cancer Research (SAKK). Protocol 30/85 comprises a double induction and one course of consolidation. Of 206 registered patients, 199 were evaluable; 118 of 199 (59%) patients entered completed all three cycles of chemotherapy. These 118 patients received a median (range) of 18 (3-44) units of red blood cells and 12 (2-61) platelet transfusions during 112 (70-129) days of hospitalization. Patients with a hemoglobin > 10 g/l, platelets > 100 x 10(9)/l, and white blood cell counts < 5 x 10(9)/l at diagnosis received fewer transfusions than patients with less favorable blood counts during the first cycle of chemotherapy (p < 0.05). Patients with FAB subtype M3 received more platelet transfusions during the first cycle. Female patients received more platelet transfusions than male patients. In multivariate analyses the participating center was the most important single factor associated with the number of red cell and platelet concentrates given per patient and cycle (p < 0.05), the number of days in hospital (p < 0.05), and the risk of premature withdrawal from the study. These data define factors associated with transfusion requirements in patients treated for newly diagnosed AML. They include severity and subtype of disease at diagnosis, age and sex of the patients, and the participating institution. Results suggest that medical decision-making varies from center to center. The participating institution is strongly associated with differences in transfusion requirements, hospitalization time, and premature withdrawal from study. Leukemia trials tend to focus on the prospective evaluation of chemotherapy or growth factors. Our results suggest that other variables, such as management strategies, should be included for prospective analysis. PMID- 8218537 TI - Effect of recombinant human erythropoietin after allogenic bone marrow transplantation. AB - The hematologic effects of recombinant human erythropoietin after allogeneic bone marrow transplantation (BMT) were studied. Nineteen patients received 150 U/kg/day of C127 mouse-cell-derived recombinant human erythropoietin (rHu EPO) as a daily continuous intravenous infusion until hematocrit exceeded 35%. These data were compared with a treatment-matched historical control group of 43 patients. RHu EPO-treated patients recovered erythropoiesis more rapidly and became independent from erythrocyte transfusions after a median of 17 days, which was 7 days earlier than the control patients. PMID- 8218539 TI - Serum erythropoietin levels in thalassemia intermedia. AB - Serum concentrations of erythropoietin (EPO) were determined by immunoassay in 45 patients with thalassemia intermedia (TI). The mean serum level of EPO was significantly higher in the thalassemic patients than in the controls, but transfused subjects had lower pretransfusional serum concentrations of EPO than untransfused ones. An inverse relationship between the serum values of EPO and total hemoglobin was observed only in the untransfused thalassemic patients. These data suggest that in TI, even a low transfusional regimen may cause a decrease in serum concentration of EPO, independent of the level of total Hb. PMID- 8218538 TI - The tolerability of continuous intravenous infusion of interleukin-3 after DHAP chemotherapy in patients with relapsed malignant lymphoma. A phase-I study. AB - The objective of this phase-I study was to establish the maximum tolerable dose of recombinant human interleukin-3 (rhIL-3) after salvage chemotherapy in patients with malignant lymphoma. Twenty-one patients with relapsed Hodgkin's disease or intermediate/high-grade non-Hodgkin's lymphoma received rhIL-3 after the second cycle of DHAP chemotherapy (cisplatin, cytosine-arabinoside, dexamethasone). Cycles 1 and 3 were given without rhIL-3. The rhIL-3 was administered as a continuous intravenous infusion for 10 days starting 48 h after chemotherapy in cycle 2. Five different dose levels of rhIL-3 (0.25, 1.0, 2.5, 5.0, and 10.0 micrograms/kg/day) were sequentially tested. At the three lowest dose levels one double-blinded placebo was included for every four patients per dose level. Low-grade fever occurred in 15/21 patients, unrelated to the dose of rhIL-3. Nausea and vomiting (grade 1-2) occurred in seven patients. Headache was dose related, with 3/4 patients at a dose of 10 micrograms/kg/day experiencing troublesome grade-2 headache precluding further dose escalation. Facial flushing developed in 3/8 patients at the highest dose levels of rhIL-3. There was a significant increase in eosinophil count during rhIL-3 (p = 0.03 cycle 2 vs cycle 1 and p = 0.002 cycle 2 vs cycle 3) without accompanying clinical signs of symptoms. No increase in basophil count was observed. There were no increased plasma levels of interleukin-6 or macrophage colony-stimulating factor (M-CSF) during rhIL-3. We conclude that rhIL-3 can be safely administered as a continuous intravenous infusion for 10 days after DHAP chemotherapy. Dose-limiting side effects, especially headache, occur at a dose of 10 micrograms/kg/day. PMID- 8218540 TI - Risk of agranulocytosis and aplastic anemia in relation to history of infectious mononucleosis: a report from the international agranulocytosis and aplastic anemia study. AB - The general objective of this study was to evaluate the risks of agranulocytosis and aplastic anemia in relation to drug use. Other potential risk factors, including history of infectious mononucleosis, were also evaluated. In an international population-based case-control study, cases of agranulocytosis and aplastic anemia and controls, who were patients with selected diagnoses, were identified from the same hospitals. Information on drug use was obtained in a structured interview. Limited information on environmental exposures and on selected items of medical history, including infectious mononucleosis, was also recorded. The possible effects of these factors on the risk of the two blood dyscrasias were evaluated. Relative risks were estimated by stratified analysis and by multiple logistic regression. Among 319 cases of agranulocytosis, 12 patients (4%) gave a history of infectious mononucleosis at least 1 year previously; among 2180 controls the corresponding number was 11 (0.5%) (multivariate relative risk estimate, 6.2; 95% confidence interval, 2.3-17). A nonsignificant elevation in the relative risk was observed for aplastic anemia. The data suggest that infectious mononucleosis may confer a long-term increase in the risk of agranulocytosis. However, the association was an unexpected one, identified in the course of multiple comparisons, and it must be independently confirmed. PMID- 8218541 TI - The acute infection-associated hemolytic anemia of childhood: immunofluorescent detection of microbial antigens altering the erythrocyte membrane. AB - The majority of acute infection-associated hemolytic diseases of infancy and childhood have been suggested to be caused by exogenic alterations of the erythrocyte surface, though laboratory methods for their further evaluation were not yet available. Investigating 96 children, the present study characterizes 72% of cases as corresponding to this type of acute acquired hemolytic anemia, which cannot be clearly related to autoantibodies against unmodified components of the host's own red cells. Using a new immunofluorescence test, the erythrocyte membrane of 80% of these children was found to be altered in vivo by nonspecific adsorption of foreign material released from the infectious micro-organisms. In 24% of cases additive binding of complement was detectable by an antiglobulin test. Thus, the adsorption of microbial antigens to the red cell surface is suggested to be one of the causes for the removal of altered erythrocytes due to phagocytosis or a complement-dependent destruction during the course of infection associated hemolytic anemia. Especially in childhood, the immunofluorescent detection of an erythrocyte sensitization in vivo provides a further characterization of this type of mostly transient hemolytic disease, which probably can be treated without any immunosuppressive drug, merely by elimination of the underlying infection. PMID- 8218542 TI - GPI Mount Scopus--a variant of glucosephosphate isomerase deficiency. AB - Glucosephosphate isomerase (GPI) deficiency is an unusual cause of hereditary nonspherocytic hemolytic anemia. The disease, inherited as an autosomal recessive disorder, is most often manifested by symptoms and signs of chronic hemolysis, ameliorated by splenectomy. We recently diagnosed GPI deficiency in a 23-year-old Ashkenazi Jewish man who displayed the typical clinical course of this disorder. The biophysical characteristics of the GPI variant are slow electrophoretic mobility, presence of only one of the two bands normally present, and extreme thermolability. To the best of our knowledge, this is the first report of GPI deficiency in a patient of Jewish descent, and we propose to designate this enzyme variant "GPI Mount Scopus". PMID- 8218543 TI - Hydroxylapatite augmentation of the atrophic maxilla--a predictable approach. PMID- 8218544 TI - There are statistics, and ... there are statistics! PMID- 8218546 TI - Dental advertising. PMID- 8218545 TI - Restoring a unilateral edentulous space with an implant supported prosthesis. PMID- 8218547 TI - The marketing plan: phase three, the seminar. PMID- 8218548 TI - Modulation of inflammatory reactions by previous contact with Escherichia coli in rats. AB - OBJECTIVE: To find out if contact with Escherichia coli had any effect on a subsequent inflammatory reaction induced by the same micro-organism. DESIGN: Controlled laboratory study. SETTING: University laboratory. MATERIAL: Male white Wistar rats divided into groups of 6 to 10. INTERVENTIONS: Pretreatment with sponges soaked in 1 x 10(9) heat killed E. coli inserted either subcutaneously into the back or intraperitoneally into the right hypochondrium, and 14 days later repeat challenge. Controls received sponges soaked either in saline with penicillin and streptomycin or with carrageenan lambda. Pretreatment with live or heat killed E. coli or E. coli endotoxin injected intradermally or intraperitoneally (controls were given saline). MAIN OUTCOME MEASURES: Number of white cells present in the inflammatory infiltrate and the peritoneal cavity, and titres of anti-E. coli antibody. RESULTS: Pretreatment of Wistar rats with heat killed or live E. coli (ATCC 25922) was followed by increase in the cellular infiltrates at the site of subsequent challenge with the same micro-organism. The effect was not related to the synthesis of anti-E. coli antibodies. CONCLUSION: Surgical patients have commonly been in previous contact with E. coli; this might affect their inflammatory reactions if they came into contact with the organism after operation. Further studies are needed to clarify the precise mechanisms and clinical relevance of these findings. PMID- 8218549 TI - Effects of ischaemia and reperfusion on liver regeneration in rats. AB - OBJECTIVE: To assess the effects of oxygen free radicals on liver regeneration in rats after 80% hepatectomy. DESIGN: Open laboratory study. SETTING: Institute of Biomedical Sciences, University of Milan, Italy. MATERIAL: Female Sprague-Dawley rats. INTERVENTIONS: After laparotomy 122 rats had ischaemia induced by clamping of the portal vein and hepatic artery, and 93 rats had manipulation of the vessels only. They were then allowed to recover before 80% hepatectomy was done. Absolute controls (n = 16) did not have a laparotomy. Mortality was recorded, and surviving rats were killed one, three, five, and seven days after operation. A further 10 rats had 80% hepatectomies and then underwent a 10 minute period of ischaemia 24 hours later. These animals were killed after three days. In yet more experiments 38 rats underwent 80% hepatectomies and were then divided into four groups: 8 were given allopurinol 50 mg/kg/day starting three days before operation; 8 were given superoxide dismutase 4.16 mg/kg intraperitoneally 30 minutes before induction of ischaemia; 12 were given verapamil 0.1 mg/kg 30 minutes before induction of ischaemia; and 10 were given saline (controls). MAIN OUTCOME MEASURES: Incorporation of tritiated thymidine into DNA, differences in liver weights, and lipid peroxide concentrations. RESULTS: 43 rats died after ischaemia/reperfusion and 19 after hepatectomy alone. Ischaemia/reperfusion caused a significant reduction in the incorporation of tritiated thymidine into DNA 24 hours after hepatectomy (p < 0.01), and significant inhibition of recovery of liver weight three (p < 0.01) and five (p < 0.05) days after hepatectomy. These effects were associated with high lipid peroxide concentrations at three days. Allopurinol (p < 0.01, p < 0.05), superoxide dismutase (p < 0.01, p < 0.01) and verapamil (p < 0.01, N.S.) reduced the effects of ischaemia/reperfusion on liver weights or lipid peroxide concentrations three days after hepatectomy. CONCLUSION: A 10 minute period of ischaemia followed by reperfusion temporarily reduces liver regeneration after 80% hepatectomy in rats. PMID- 8218550 TI - Pulmonary infections of gut origin after major liver resection in rats. AB - OBJECTIVE: To assess the incidence of translocation of enteric bacteria to the lungs in the early postoperative period (1, 2, 4, and 6 hours) after sham operation, 70% hepatectomy, and 90% hepatectomy. DESIGN: Randomised laboratory experiment. SETTING: University department. MATERIAL: 96 Adult male Sprague Dawley rats. INTERVENTIONS: Sham operation (n = 24), 70% hepatectomy (n = 36), and 90% hepatectomy (n = 36). Injection of 1 ml (1.5 x 10(7) cpm/rat) 125I labelled heat-killed Escherichia coli 15 minutes before the animals were killed. MAIN OUTCOME MEASURES: Arterial blood gas analyses, wet: dry weight ratio of lungs, and measurements of pulmonary isotopic flux (amount of 125I radioactivity in the lungs compared with that in the blood) 1, 2, 4, and 6 hours after operation. Quantitative microbiology of lungs. RESULTS: There was no pulmonary oedema in those rats that underwent sham operation. Pulmonary oedema had developed by 6 hours after 70% hepatectomy and by 2 hours after 90% hepatectomy. The lung:blood ratio of 125I-labelled bacteria increased as the pulmonary oedema developed, but pulmonary oxygen exchange was not influenced during the first 6 hours after hepatectomy. The incidence of bacterial translocation increased with the extent of hepatectomy and with the length of time after operation. CONCLUSION: Bacterial translocation from the gut could lead to pulmonary infection after major liver resection in rats. PMID- 8218551 TI - Changes in the surgical treatment of gallstones during a 10 year period. AB - OBJECTIVE: To investigate changes in the surgical treatment of gallstones during a 10 year period. DESIGN: A retrospective study of medical records. SETTING: A community hospital serving a population of 108,000 inhabitants. SUBJECTS: All patients having their first operation for gallstones during the periods 1976-1978 and 1986-1988. RESULTS: The annual frequency of operations for gallstones decreased from 2.01 to 1.13/1,000 inhabitants, and the corresponding frequency of operations on the common duct decreased from 0.39 to 0.28. The percentage of urgent operations increased from 19 to 47. CONCLUSION: A decline in the prevalence of cholelithiasis or a more restrictive attitude of elective operations for gallstones, or both, would explain the overall reduction in surgery for gallstones. The introduction of endoscopic sphincterotomy has considerably changed the treatment of cholelithiasis. The increased age of the patients and higher percentage of urgent operations has not resulted in any increase in postoperative morbidity and mortality. PMID- 8218552 TI - Primary carcinoma of the gallbladder: operative experience during a 16 year period. AB - OBJECTIVE: To evaluate the results of operations for primary carcinoma of the gallbladder during the 16 year period 1975-1990. DESIGN: Retrospective study. SETTING: University affiliated hospital in Switzerland. SUBJECTS: 55 consecutive patients with primary carcinoma of the gallbladder. INTERVENTIONS: Resection with curative and palliative intent was done in 34 (62%) and in 10 (18%), respectively. Thirty nine (62%) had simple cholecystectomy and two (4%) radical resections; the remaining 14 (25%) had palliative operations. RESULTS: 23 Patients (42%) had early tumours (confined to the gallbladder wall, TNM stages I and II), and 32 (58%) had late tumours (TMN stages III and IV). A tumour of the gallbladder was suspected from preoperative ultrasonography in 20 of 37 examined patients (54%); 17 (31%) had occult lesions. Five patients died during the 30 day postoperative period (9%), and the overall median survival was 8.6 months. One and five year survival rates were 40% and 7%, respectively. Only four patients had long term cures after cholecystectomy alone. CONCLUSION: There was a high incidence of locoregional recurrence among patients with stage II disease, and this group benefit from more radical resections. For advanced tumours, palliation alone is preferable. PMID- 8218553 TI - Effect of fibrin sealant on the integrity of colonic anastomoses in rats with faecal peritonitis. AB - OBJECTIVE: To assess the influence of fibrin adhesive on the healing of colonic anastomoses in rats with and without faecal peritonitis. DESIGN: Controlled study. SETTING: Laboratory for experimental surgery, Erasmus University Rotterdam, The Netherlands. MATERIAL: 120 male Wag/Rij rats. INTERVENTIONS: All rats had a single layer end-to-end anastomosis fashioned with 7/0 polypropylene. Faecal peritonitis was then induced in half of the rats by placement of 200 mg powdered autoclaved rat faeces in the peritoneal cavity near the anastomosis. Rats were allocated to one of four groups (n = 30 in each): 1--control; 2- additional sealing with fibrin glue; 3--peritonitis alone; and 4--peritonitis with fibrin glue. MAIN OUTCOME MEASURES: Body weight, adhesion formation, anastomotic bursting pressure and collagen concentration around the anastomosis on days 2, 4, and 7 in 10 rats from each group. RESULTS: 11 rats died of peritonitis before the experiment was completed. Peritonitis caused increased formation of adhesions and abscesses, with or without fibrin sealant. Bursting pressure at the anastomosis was significantly reduced in peritonitis compared with controls on days 4 and 7, and this was not prevented by fibrin. Sealing of anastomoses resulted in lower bursting pressures on day 4 in control animals. Collagen concentration was significantly reduced in peritonitis with or without fibrin sealant on days 4 and 7, and after fibrin sealing of control anastomoses. CONCLUSION: Faecal peritonitis reduced mechanical strength and collagen concentration of colonic anastomoses, and this was not prevented by additional sealing of the anastomosis with fibrin sealant. PMID- 8218554 TI - Calcification of a polytetrafluoroethylene haemodialysis graft. PMID- 8218555 TI - Left-sided inferior vena cava and thrombosis. PMID- 8218556 TI - Leiomyosarcoma in a Littre's hernia. PMID- 8218557 TI - Delayed large bowel obstruction after blunt abdominal injury. PMID- 8218558 TI - [Two site-specific endonucleases from the thermophilic strain Bacillus species LU11]. AB - Upon screening of natural strains of thermophilic bacteria, a strain has been found which contains two restriction endonucleases. One of those, BspLU11II, is an isoschizomer of XbaI, while the other one, BspLU11I, recognizes the new palindromic sequence 5'-A decreases CATGT-3' and cleaves it as indicated by the arrow. Functionally pure enzymes were obtained by stepwise chromatography with blueagarose, hydroxyapatite and heparin-Sepharose. The restriction endonuclease BspLU11I produces sticky ends identical to those produced by the restriction endonuclease NcoI; hence a combination of BspLU11I and NcoI can be used for enzymatic selection of recombinant DNA. The recognition sequence of BspLU11I contains the ATG codon and can be used to construct expression vectors for chemically synthesized genes. PMID- 8218559 TI - [Bioluminescence and bioluminescent analysis: development of certain aspects of the problem over the last decade]. AB - Recent data from gene engineering, kinetic and fluorescent studies concerning the structure and functions of firefly luciferase are reviewed. Some new trends in the development of bioluminescent methods of control over bacterial contaminations, dynamics of intracellular processes and methods of bioluminescent detection in immuno- and DNA-assays are described. Possible applications of luciferase genes as markers are considered. PMID- 8218560 TI - [Thrombin: structure-function relationship in biochemical interactions]. AB - Data on the content and localization of the recognition site (exosite) for high molecular weight substrates in the thrombin molecule have been summarized. It has been shown that this center, which binds anion sites of macromolecules, plays a key role in regulation of thrombin activity. Data of a proteolytic mechanism of platelet receptor activation by thrombin are reported. Prospects in biomedical studies of thrombin derivatives are discussed with the emphasis on developing new therapeutic tools and combined courses of thrombolytic therapy. Possibilities are discussed of developing a computer model of thrombin interactions for theoretical and applied purposes. PMID- 8218561 TI - [Properties of a nitrite reductase inhibitor protein from Pseudomonas aeruginosa]. AB - The amino acid composition and major physico-chemical properties of the "nonblue" copper protein isolated earlier from Pseudomonas aeruginosa have been determined. It has been found that the azurin oxidase, cytochrome c551 oxidase and superoxide dismutase activities of the enzyme are inhibited by this protein. The inhibition seems to be due to the protein interaction with the electron-accepting center of nitrite reductase. PMID- 8218562 TI - [H(+)-ATPase from yeast vacuoles is inhibited by heparin]. AB - Heparin (20-40 micrograms/ml) inhibits by 50% both the ATP hydrolase and the delta pH formation in isolated yeast vacuoles. The GTPase activity is not inhibited under these conditions. ATP prevents this inhibition, being added 10 min before heparin. Heparin suppresses the phosphorylation of vacuolar proteins in vitro. It is supposed that the protein kinase, similar to casein kinase I, participates in the regulation of activity of the vacuolar ATPase. PMID- 8218563 TI - [Purification and immunochemical characteristics of neutral Mn-dependent DNAase of chromatin]. AB - A scheme for purification of neutral Mn-dependent chromatin DNAase has been developed. The two-step purification procedure, which includes chromatography on hydroxyapatite and isoelectrofocusing, allows one to obtain preparative amounts of the enzyme having a specific activity of more than 3000 u./mg, molecular mass of 41 kDa and pI of 9.2. PMID- 8218565 TI - [The effect of structural organization of cholesterol aggregates in aqueous organic media on its oxidation reaction, catalyzed by cholesterol oxidase]. AB - Cholesterol oxidation by cholesterol oxidase in homogeneous water-organic mixtures without the use of surface-active agents and the effects of reaction medium parameters on this process have been studied. It has been shown that the nature of the organic solvent, buffer salts, pH and the "age" of the cholesterol solutions determine the formation of the "substrate" properties of sterol molecules in the aggregates which is manifested as changes in the kinetic parameters of the oxidation reaction and in the spectrophotometric characteristics of the enzymatic oxidation product, 4-cholesten-3-one. Such changes are the most vividly pronounced during oxidation of "aged" cholesterol solutions prepared 24 hrs before the reaction and are concomitant with significant reductions in the maximal reaction rate, Km values of cholesterol oxidase for cholesterol and the effective molar extinction coefficient for 4 cholesten-3-one. Sonication of "aged" cholesterol solutions partly restores these indices. The observed phenomena seem to be due to the different extent of aggregation of cholesterol molecules in solutions. Other factors influencing the value of the molar extinction coefficient for 4-cholesten-3-one, such as hypochromicity and stray light, are also discussed. The enzyme has a broad pH optimum at pH 7.0. The Michaelis constant for cholesterol does not appreciably change in the pH range studied (6.0-8.0) and constitutes approximately 15 microM for freshly prepared cholesterol solutions containing 10% propanol-1. The catalytic constant measured under the same conditions is about 22 s-1 at 20 degrees C and pH 7.0. The stability of cholesterol solutions is strongly influenced by the pH of the reaction medium, nature of the organic solvent and buffer salts. Weakly alkaline solutions prove to be the most stable ones. Regardless of the nature of the buffer salt its concentration in the range of 0.02-0.2 M does not affect the reaction. PMID- 8218564 TI - [A comparative study of the structural state of skeletal muscle and smooth muscle fiber tropomyosin in ghost skeletal muscle fibers by a fluorescent probe method]. AB - The structural state of skeletal muscle and smooth muscle fiber tropomyosins in ghost fibers of skeletal muscles has been studied by means of polarization microfluorimetry. Tropomyosins and F-actin of ghost fibers were labelled with N (iodoacetyl)-N-(1-naphthyl-5-sulfo)-ethylenediamine (1,5-IA-EDANS) or the phalloidin-rhodamine complex, respectively. It has been found that skeletal tropomyosin bound to ghost muscle fibers is more flexible in comparison with smooth muscle tropomyosin. The flexibility of the thin filaments of the ghost fibers labelled in F-actin by the phalloidin-rhodamine complex and containing smooth muscle tropomyosin is higher than that of the thin filaments containing the bound skeletal muscle protein. PMID- 8218566 TI - [Metalloproteinase of Bacillus mesentericus, strain V-313]. AB - A homogeneous metalloproteinase has been isolated with a 28% yield from the culture fluid of Bacillus mesentericus, strain B-313. The isolation procedure included chromatography on bacitracin-silochrome and gel filtration on Acrylex P 10 and Sephadex G-75. The enzyme has a molecular mass of 41,000 Da; its N terminal sequence, which appears as A-A-T-T-G-T-G-T-T-L-K-G-K-T-V-S-L-N-I, is identical with that of the B. amyloliquefaciens enzyme. Like other metalloproteinases, the enzyme is inhibited by o-phenanthroline and EDTA, has an activity maximum at 55 degrees C and pH 6.5-7.2, is stable at pH 7.0-9.5 and at temperature below 45 degrees C for several hours, and is irreversibly inactivated in acid media. As can be judged from the kcat/Km ratio dependence on pH, two ionogenic groups with pKa of 7.4 and 6.2 are involved in the catalytic act, presumably the imidazol group of histidine and the carboxylic group. Within synthetic peptides the enzyme hydrolyzes the bonds formed by the amino group of hydrophobic amino acids, mostly of leucine residues. PMID- 8218567 TI - [Inhibition of cathepsin G and elastase from human granulocytes by multiple forms of the Bowman-Birk type of soy inhibitor]. AB - A classical soybean inhibitor (Bowman-Birk inhibitor, BBI 2-IV) and two high molecular weight glycine-enriched inhibitors of the same type (3-II and 4-II) have been isolated, purified to homogeneity and characterized. All of the BBI isoforms have been found to effectively inhibit cathepsin G and human granulocyte elastase. The constants for leucocyte cathepsin G inhibition by classical BBI 2 IV (Ki = 1.2 x 10(-9) M) and high molecular mass BBI 3-II (Ki = 8.0 x 10(-8) M) as well as for leucocyte elastase inhibition by high molecular mass BBI 3-II (Ki = 1.1 x 10(-7) M) have been determined. PMID- 8218568 TI - [Elastase from the hepatopancreas of the king crab]. AB - Using ion-exchange chromatography on DEAE-Sepharose and gel-filtration on Sephacryl S-200, a homogeneous preparation of elastase with a specific activity towards Boc-(Ala)3-pNA of 3.7 u./mg has been isolated from the hepatopancreas of the king crab Paralithodes camtschatica. The molecular mass and isoelectric point for the enzyme are equal to 28500 Da and 4.5, respectively. The amino acid composition of the isolated protease has been established. Analysis of catalytic properties of the enzyme revealed that the maximal elastase activity is observed at pH 8.0-8.5; the Km and kcat values for Suc-(Ala)3-pNA are 4 mM and 3 s-1, respectively. The enzyme activity is fully inhibited by elastinal and diisopropylfluorophosphate, but not by N-ethylmaleimide, 2-mercaptoethanol, p chloromercuribenzoate, EDTA, or o-phenanthroline, which makes it possible to refer the enzyme to the class of serine elastases. The activating effect of crab elastase was demonstrated in the presence of inorganic salts. The elastase is stable in neutral and alkaline solutions containing detergents as well as at temperatures below 45 degrees C (pH 8.0). PMID- 8218569 TI - [Study of complex formation between NAD-kinase and glutamate dehydrogenase, isolated from rabbit liver hyaloplasm]. AB - Evidence for the localization of up to 25-30% of the total glutamate dehydrogenase activity in rabbit liver cell hyaloplasm has been obtained. Differences were revealed in the properties of glutamate dehydrogenase from the hyaloplasm and mitochondria. The ratios of activities in the amination/deamination reactions as measured at optimal values of pH for the mitochondrial and liver enzymes were 3.7 and 1.0, respectively. The enzyme preparations isolated from the both fractions appeared to be electrophoretically homogeneous and had a subunit molecular mass of about 56 +/- 2 kDa. Fresh preparations of mitochondrial and hyaloplasm liver glutamate dehydrogenase contained several oligomeric forms, predominantly with M of 350 and 280 kDa, respectively. Data from gel-filtration on Sephacryl S-300 are suggestive of a complex (M = 800 kDa) formation between liver hyaloplasm glutamate dehydrogenase (280 kDa) and NAD-kinase (440 kDa); this reaction is accompanied by simultaneous activation of these enzymes (3.5- and 2.4-fold, respectively). PMID- 8218570 TI - An improved chemical substitute for fetal calf serum for the micronucleus test. AB - The routine use of the micronucleus test in the mutagenicity evaluation of xenobiotics is limited by high cost and limited availability of fetal calf serum. On the other hand, there are disadvantages, such as hypotonic damage and clumping of cells, associated with the use of mineral medium substitutes for fetal calf serum. Alternatively, we recommend a chemical medium containing Hanks' buffered salt solution, 1% (w/v) bovine serum albumin, and 0.15% (w/v) ethylenediaminetetraacetic acid, final pH 7.4, to preserve morphology, density and homogeneity of bone marrow cells. Mast cell granules are efficiently removed from rat bone marrow preparations by washing twice with this medium. The morphological preservation of cells is further enhanced by fixation with 70% (v/v) ethanol for 5 min. The proposed medium provides a cost-effective and convenient substitute for fetal calf serum with substantially improved quality of bone marrow preparations for the micronucleus test. PMID- 8218571 TI - The use of hydrophobic adhesive tape to produce miniature wells on microscope slides. AB - Hydrophobic adhesive tape was used to produce miniature wells on microscope slides for staining several sections of tissue with minimal amounts of cytochemical reagents. The wells could be tailored to individual specifications and the method allowed coverslips to be mounted close to the sections using either aqueous or xylene based mounting media. This method was especially useful for multiple immunolabelling of serial semithin cryosections. PMID- 8218572 TI - Zinc-specific N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide as a selective nontoxic fluorescence stain for pancreatic islets. AB - Separation of the endocrine from the exocrine pancreatic tissue by fluorescence activated sorting has been limited by the lack of an ideal fluorescent label for islet tissue. Our studies indicates the zinc-specific stain N-(6-methoxy-8 quinolyl)-para-toluenesulfonamide (TSQ), has characteristics ideal for use as a fluorescent label for islet tissue. Dispersed rat pancreas cells stained with TSQ produced bright blue fluorescence when excited by UV light (peak emission wavelength at 480 nm, maximal excitation at 365 nm). The fluorescence was specific for islet tissue as confirmed by counterstaining with the islet-specific stain dithizone and there was minimal background staining of exocrine tissue. Stained tissue remained brightly fluorescent for 2 hr, with some fading by 4 hr. Injection of TSQ into rats at a concentration sufficient to produce staining of islets produced no toxicity discernible at 4 months. The viability of isolated rat islets stained with TSQ was maintained as shown by supravital staining, in vitro secretion of insulin, and reversal of diabetes after transplantation of stained islets into diabetic syngeneic recipients. PMID- 8218573 TI - Suitability of different protein A-gold markers for immunogold-silver staining in paraffin sections. AB - An incubation protocol to immunolabel Lowicryl semithin sections was applied to paraffin probes. To improve the labeling density, colloidal gold complexes of different preparations and sizes were compared. The type of colloidal gold preparation used was found to affect the specificity of the immunostaining. Gold colloid of 5 nm diameter particle size prepared with white phosphorus minimized nonspecific background labeling of beta-casein in paraffin embedded sections of the mammary epithelium of pregnant mice. Gold colloids of 5 nm and 9 nm diameter particle size prepared in varying concentrations of tannic acid generated significant nonspecific staining in similar tissue preparations. PMID- 8218574 TI - A simple and inexpensive device for freeze substitution at 183 K/-90 C. AB - The freeze substitution device described here consists of commonly available materials, is easy to construct and to handle and provides maximal working safety. An adequate mass of copper and/or brass, serving as holder for 16 cryovials, is chilled to liquid nitrogen temperature. The vial holder is placed in a precooled thermos flask filled with ethanol and stored in an ultrafreezer at 193 K/-90 C. This ensures that the vial holder maintains temperatures of about 183 K/-90 C for more than 12 hr to minimize the risk of ice recrystallization. PMID- 8218575 TI - Three-way differentiation of Chinese hamster ovary chromosomes by immunoperoxidase technique using a monoclonal anti-bromodeoxyuridine antibody. AB - A new permanent staining procedure for sister chromatid differentiation (SCD) in cultured Chinese hamster ovary cells has been established by combining the three way differentiation in third mitosis (M3) chromosomes and the immunoperoxidase reaction developed with 3,3'-diaminobenzidine using a monoclonal anti bromodeoxyuridine (BrdU) antibody. This procedure allows SCD at very low BrdU concentrations, and the evaluation of the sister chromatid exchange frequencies on a per cell-cycle basis. PMID- 8218576 TI - A perfusion chamber with temperature regulation. AB - When investigating microscopic preparations perfusion chambers allow exchange and regulation of different solutions and ensure their constant flow in the sample chamber. Temperature deviations, however, may be problematic. We describe a new chamber that contains an additional circulation system which regulates the inside temperature using an external thermostat. An integrated thermometer probe records the sample temperature, which appears on a monitor. The glass chamber, measuring 75 x 35 x 3 mm, provides good optical quality and is compatible with every type of microscope. PMID- 8218577 TI - A double staining technique using 5-bromo,4-chloro-3-indolyl-beta-D galactopyranoside (X-gal) and immunoperoxidase in whole Drosophila embryos. AB - We have developed a double staining method using 5-bromo,4-chloro-3-indolyl-beta D-galactopyranoside X-gal and immunoperoxidase for whole Drosophila embryos. The dechorionated embryos are fixed in heptane saturated with 4% formaldehyde, then in heptane and 50% methanol. Fixed embryos are devitellinized with a tungsten needle and processed for immunoperoxidase staining immediately prior to peroxidase color development. The embryos are stained with X-gal, then peroxidase staining is resumed. This procedure enables us to observe cells stained with both X-gal and a specific antibody in whole embryos. PMID- 8218578 TI - Combined lectin binding and PAS/alcian blue staining in glycol methacrylate sections. AB - Evaluation of cryofixation and paraffin and glycol methacrylate embedding showed that lectin binding was essentially independent of the embedding medium. Fluorescence intensity increased in the following order: glycol methacrylate, paraffin and cryostat sections. The optical resolution increased in the reverse order. Semi-thin glycol methacrylate sections provided satisfactory fluorescence intensities and the best resolution of all embedding techniques applied. Furthermore the lectin treated sections can be stained further using routine histological or specific histochemical methods. The potassium hydroxide/alcian blue/periodic acid-phenylhydrazine-Schiff method was used successfully to demonstrate sulfated and nonsulfated sialomucins. Lectins combined with mucin histochemistry allowed visualization of specific sugar residues in the same glycol methacrylate plastic section. PMID- 8218579 TI - Pathobiochemical aspects of cytoskeleton components. AB - This review summarizes pathobiochemical aspects of diseases, in which cytoskeletal components play a crucial role in pathogenesis. An attempt to classify the disorders on the basis of phenotypic changes that occur in microfilaments, intermediate filaments and microtubuli was unsuccessful. Three groups of disorders are presented: 1. cytoplasmic inclusions in specific diseases (merely descriptive); 2. diseases with genetic defects in cytoskeletal proteins (a chain of causality from defect to phenotype, in some cases with large gaps); 3. diseases with suspected involvement of cytoskeleton (hypothetical causal chain). Microfilaments are involved in certain pathogenetic processes on account of defects in their associated proteins; in Duchenne muscular dystrophy, dystrophin is defective, while the defective protein in Rett syndrome is synapsin. Defects in spectrin and membrane anchor proteins lead to disorders of the red cell membrane skeleton (congenital haemolytic anaemias). Intermediate filaments accumulate in some types of cytoplasmic inclusions, together with ubiquitin (Mallory bodies, desmin accumulation in some myopathies and others). A pathogenetic interpretation of this phenomenon is lacking. A genetic defect in certain types of keratin is the cause of epidermolysis bullosa. Interesting preliminary results are reviewed that reveal the crucial role of cytoskeletal components in a further group of diseases (intrahepatic cholestasis, Alzheimer disease, pemphigus). These disorders are currently under investigation, or are of theoretical interest with respect to the cytoskeleton. Specific reactions of cytoskeletal components in serum, which might be used diagnostically, have not been found. PMID- 8218580 TI - Group I and group II phospholipases A2 in serum in uraemia. AB - Time-resolved fluoroimmunoassays were used for the detection of pancreatic group I and synovial-type group II phospholipases A2 in sera of patients suffering from chronic renal failure before and after haemodialysis. The concentration of group I phospholipase A2 was ten-fold higher in sera of uraemic patients than in healthy controls. There was no significant difference in the concentrations of group I phospholipase A2 in serum before and after haemodialysis. The concentration of group II phospholipase A2 was only marginally increased in sera of uraemic patients, compared with healthy controls. There was no significant difference in the concentrations of group II phospholipase A2 before and after haemodialysis. The results indicate that the metabolism of group I phospholipase A2 differs from that of group II phospholipase A2 in chronic renal failure. PMID- 8218581 TI - Re-evaluation of cerebrospinal fluid angiotensin-converting enzyme activity in patients with 'probable' Alzheimer's disease. AB - Angiotensin-converting enzyme activity was measured in lumbar cerebrospinal fluid from patients with 'probable' Alzheimer's disease (n = 17) and age-matched controls (n = 19), using a spectrofluorimetric method. In contrast to a previous finding, no statistically significant difference in the mean (specific) angiotensin-converting enzyme activity was found between the two groups. No correlation existed between (specific) enzyme activity and severity of dementia in the Alzheimer's disease patients. We conclude that angiotensin-converting enzyme in cerebrospinal fluid does not appear to be useful as a potential antemortem marker for Alzheimer's disease. PMID- 8218582 TI - Investigation of total and conjugated bilirubin determination during the neonatal period. AB - During the neonatal period, total and conjugated bilirubin determinations are necessary to identify the origin of jaundice, to predict its evolution and to treat it. We discuss the results obtained in 108 neonates (less than 15 days old), undergoing phototherapy or not, using a colorimetric diazo reaction and dual wavelength reflectance with a Kodak Ektachem analyzer. Concerning total bilirubin determination, the methods correlate well (r > 0.96). Discrepancies are observed for conjugated or "direct" bilirubin, and high performance liquid chromatography was carried out in order to explain them. The chromatograms show 4 neonate samples with only classic mono- but no di-glucurono-conjugate fractions, whereas all the neonates present two unusual fractions (I and II) not seen in adults. A correlation was found between the amount of fraction II and the conjugated bilirubin determined by diazo reaction and between fraction I and the conjugated bilirubin obtained in the Kodak Ektachem assay. A better correlation between fraction I and conjugated bilirubin on Kodak was observed (r = 0.79, vs r = 0.66) when the newborns were submitted to phototherapy. Moreover, fraction II and conjugated bilirubin measured by the diazo reaction on Hitachi 717 rose significantly. In conclusion, total bilirubin is accurately determined during the neonatal period; for conjugated or "direct" bilirubin determination, our study points out significant differences. Further investigation will determine the nature of the fractions observed by liquid chromatography in neonatal sera, and the components actually determined by the automatized methods usually employed. PMID- 8218583 TI - A high performance liquid chromatography method for the determination of glycosaminoglycans in human blood. AB - A method is described for the determination of plasma and serum glycosaminoglycans, which can be used in any laboratory equipped with an HPLC system. It is based on the sequential application of chondroitinases AC and ABC and separation of the resulting disaccharides by high-performance liquid chromatography. All reagents are commercially available. This simple and rapid separation yields an accurate quantification and an exact distribution pattern. The determination of glycosaminoglycan disaccharides is linear between 7 and 7000 mumol/l with coefficients of variation between 3.0 and 7.7% for serum and between 2 and 14% for plasma. The recovery of the assay ranged from 93 to 106% for different concentrations of glycosaminoglycan disaccharides. This HPLC method may therefore be considered as a candidate reference method. PMID- 8218584 TI - A highly sensitive immunoenzymometric assay for the determination of angiogenin. AB - A polyclonal antibody to human recombinant angiogenin was prepared in rabbits using a Pam3CysSerGly conjugate. The antibody was then used to develop the first highly sensitive enzyme-labelled immunometric assay for this vascularisation inducing and tumour associated protein. The assay was suitable for quantification of angiogenin in body fluids between 2.5 and 0.05 micrograms/l. The mean intra assay imprecision was 6.0% and the inter-assay imprecision 7.9%. Angiogenin in human plasma was found to lie in the range of 0.38 to 0.11 mg/l with a mean of 0.25 +/- 0.07 mg/l. PMID- 8218585 TI - Establishment of reference ranges for cortisol in neonates, infants, children and adolescents. AB - Cortisol was determined in the sera of 687 normal, healthy probands between the ages of 5 days and 18 years (neonates, infants, children and adolescents), using a fluorescence polarization immunoassay (FPIA) on the TDx from Abbott Laboratories. The proband collective was divided into 9 age groups and each group into males and females. In accordance with the recommendations of the International Federation of Clinical Chemistry, the 95% scatter range was taken as the reference range. Only a few reference groups showed a normal Gaussian distribution. In addition to the 50th percentile, the 2.5th and 97.5th percentiles were determined for all reference groups. Minimal and maximal values were also determined. The U-test of Mann & Whitney was used to test for significant differences between the individual reference groups. Groups showing no significant differences were combined, and reference ranges were finally calculated for cortisol in the serum of normal, healthy neonates, infants, children and adolescents. The serum cortisol concentration showed a significant increase with age. In the 14-15 years age group, there was also a significant difference between males and females. PMID- 8218586 TI - Laboratory experience and guidelines for avoiding false positive polymerase chain reaction results. AB - Despite the widespread use of polymerase chain reaction (PCR) for diagnosis of infectious diseases, the technology has not been generally introduced into routine diagnostic laboratories. One of the most serious problems which has influenced the acceptance of this technology is the occurrence of false positive PCR results. This study describes the experience, in a hospital laboratory setting, of using PCR for the diagnosis of heat-labile enterotoxin-producing E. coli, M. tuberculosis, M. paratuberculosis and human papillomavirus. Results indicate that a build-up of amplicons, generated during the amplification process in the laboratory, is the main source of PCR-contamination. Protocols are described that include both physical and chemical procedures to prevent contamination. The use of photo-induced psoralen is recommended for those laboratories already involved in PCR work where amplicons are likely to be present. An enzymatic system (uracil-N-glycosylase) was evaluated and is recommended for workers intending to start diagnostic PCR. Attention was given to simple control measures which are easily implemented in a routine diagnostic laboratory. Protocols such as these are likely to have a major impact on the introduction of PCR-based methods into routine laboratories. PMID- 8218587 TI - Comparison of two time-resolved fluoroimmunoassays (TR-FIA), as applied to oestriol in human serum and progesterone in bovine milk. AB - We compared two time-resolved fluoroimmunoassay systems for measuring free oestriol in human serum and progesterone in bovine milk. By reading the fluorescence of europium complex of 4,7-bis(chlorosulphophenyl)-1,10 phenanthroline-2,9-dicarboxylic acid in solution, the measuring range is increased for both oestriol (10-50,000 ng/l instead of 25-50,000 ng/l) and for progesterone (10-50,000 ng/l instead of 25-10,000 ng/l). In addition, the interassay coefficients of variation were lowered from 9.5 to 5.7% for oestriol and from 7.5 to 5.4% for progesterone, at the smaller hormone concentrations detectable by each method. PMID- 8218588 TI - "Titre" is not an internationally recognized quantity. PMID- 8218589 TI - Goals for imprecision derived from the "state of the art". PMID- 8218590 TI - Determination of potassium by dry reagent carrier technology: a multicentre evaluation. AB - We describe the construction, the reaction principle and the performance of Reflotron K+, a new Reflotron test for the quantitative determination of potassium in serum and heparinized plasma. The reaction principle is based on the introduction of the potassium cation via valinomycin into a non-polar phase; the accompanying loss of protons from the non-polar phase is detected by the colour change of a pH indicator. The multicentre evaluation of the reagent carrier system showed in median CVs of < 0.9% (within-series in heparinized plasmas) and 1.3% (run-to-run in control sera). The recovery in control sera was +/- 4% for seven laboratories. In the method comparison with flame emission spectrometry, using sera and heparinized plasma samples, regression analysis yielded correlations with slopes of 1.00 +/- 0.04 (median slope 1.005) and negligible intercepts. The reagent carrier system showed a linear response in the measuring range 2-12 mmol/l. Bilirubin (up to 513 mumol/l), triacylglycerols (up to 5,7 mmol/l), sodium (135-189 mmol/l) and ammonium ions (up to 590 mumol/l) did not interfere with the test. Comparison with the results from flame atomic emission spectrometry shows that the recoveries of Reflotron K+ and the direct potentiometric method are slightly and similarly influenced by total protein. With a panel of 28 drugs tested, no interference could be detected. Reflotron K+ provides a precise and reliable procedure for the measurement of potassium in serum and heparinized plasma. PMID- 8218591 TI - Phenotypic and functional modulation of interleukin-2-activated peripheral blood mononuclear cells by anti-CD3 and anti-CD28 antibody. AB - For effective adoptive cancer immunotherapy, not only killer lymphocytes (cytotoxic T cells or NK cells) but also helper T cells are considered to be beneficial. The conventional culture of human lymphocytes with high-dose of recombinant interleukin -2 (rIL-2) yields a high proportion of killer cells (CD8+ or CD56+ cells) but is usually accompanied by a decrease in the proportion of CD4+ cells. Peripheral blood mononuclear cells (PBMC) stimulated with anti-CD3 monoclonal antibody (10 ng/ml) in the absence of rIL-2 during the initial 48-hr period of cultivation followed by the addition of rIL-2 (200 Japan reference units/ml) (referred to as anti-CD3-rIL-2) resulted in CD4+ cells expanding 8.0- to 63.3-fold at day 12-14. When PBMC were cultivated with rIL-2 alone, or with rIL-2 together with anti-CD3 initially, CD4+ cells expanded 1.7-6.2- or 5.7-36.9 fold, respectively. The expansion of CD4+ cells from PBMC in the anti-CD3-rIL-2 cultures was enhanced by the addition of anti-CD28 monoclonal antibody at the initiation of cultures (500 ng/ml) (referred to as anti-CD3/anti-CD28-rIL-2) (12.1- to 127.8-fold expansion). The anti-CD3-rIL-2 and anti-CD3/anti-CD28-rIL-2 cultures also demonstrated a lesser expansion of CD3-CD56+ cells (NK cells). The PBMC in the anti-CD3/anti-CD28-rIL-2 cultures showed low cytotoxic activity per cell; however, the cytotoxic activity per total culture was comparable to that of PBMC expanded with rIL-2 alone because of the larger total expansion of the former culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218592 TI - IL-1 alpha inhibits human hair follicle growth and hair fiber production in whole organ cultures. AB - In this study we have used a recently developed human hair follicle whole-organ culture system to investigate the effect of IL-1 alpha on hair follicle growth and hair fiber production. In the presence of 10 ng/ml IL-1 alpha, the growth of cultured human hair follicles ceased within 2-4 days, whereas control hair follicles grew for a period of 7-10 days. IL-1 alpha also inhibited hair fiber growth, but with an onset which occurred 3 days later than that of follicle growth inhibition. An IC50 value of approximately 30 pg/ml was obtained for IL-1 alpha inhibition of follicle growth. Incubation of hair follicles with IL-1 alpha resulted in a rapid, transient reduction in the rate of whole-follicle DNA synthesis. 1000-fold molar excess of IL-1 receptor antagonist prevented IL-1 induced follicle growth inhibition, while antagonist alone was without effect. The selective PKC inhibitor, Ro 31-7549, augmented IL-1-induced inhibition of hair follicle growth, but did not itself affect hair follicle growth. These findings indicate that IL-1 alpha exerts a rapid antiproliferative effect on hair follicles, and that inhibition of hair fiber growth is a secondary response. Thus, IL-1 may play a role in the pathophysiology of inflammatory hair loss conditions, such as alopecia areata, through a direct growth-inhibitory effect on hair follicles. PMID- 8218593 TI - Independent transcriptional and posttranscriptional regulation of the two tumor necrosis factor receptors in promyelocytic HL-60 cells. AB - Two separate tumor necrosis factor (TNF) receptors of approximately 55 kDa (TNF R55) and 75 kDa (TNF-R75) have been identified. The role of protein kinase A activation by dibutyryl cAMP (dbcAMP) and of protein kinase C activation with phorbol myristate acetate (PMA) for transcriptional and posttranscriptional regulation of the two receptors was investigated in promyelocytic HL-60 cells. Incubation with dbcAMP or the adenylate cyclase agonist forskolin caused an increase in the level of TNF-R75 mRNA while TNF-R55 mRNA was unaffected. The half life of transcripts for both TNF-R55 and TNF-R75 was unaffected as judged by disappearance of mRNA after inhibition of transcription with actinomycin D. Thus the transcription of the TNF-R75 gene seemed to be enhanced by activation of protein kinase A. This enhancement was not dependent on de novo protein synthesis. Incubation with PMA did not affect the mRNA level of any of the TNF receptors. Both TNF-R55 and TNF-R75 mRNA showed a prolonged half-life after incubation with the inhibitor of protein synthesis cycloheximide, indicating superinduction of the genes. Our results demonstrate that the two TNF receptors can be regulated differently at the transcriptional level and that both transcriptional and posttranscriptional regulation occurs. PMID- 8218594 TI - Insulin-like growth factor-1 activity is inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, and interleukin-6. AB - With evidence that several proteins inhibit insulin-like growth factor (IGF) activity, we evaluated whether cytokines, which are elevated in many catabolic states, also affect IGF-1-mediated proteoglycan synthesis. Cartilage from hypophysectomized rats was exposed to the cytokines interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6) in the presence or absence of IGF-1. IL-1 alpha inhibited IGF-1-stimulated proteoglycan (PG) synthesis > 95% at 20 ng/ml (p < 0.01). TNF-alpha and IL-6 caused a maximum inhibition of 56 and 54%, respectively, both at 200 ng/ml. Only in the absence of IGF-1 did IL-1 alpha inhibit PG synthesis below unstimulated levels, suggesting that although IL-1 alpha can directly inhibit PG synthesis, IL-1 alpha, TNF alpha, TNF-alpha, and IL-6 each promotes cartilage loss also by inhibiting IGF-1 mediated anabolism. PMID- 8218595 TI - Interleukin-6 and aging: blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction. AB - Interleukin-6 (IL-6) is a multifunctional cytokine that is proving to be a major contributor to the acute phase inflammatory response. IL-6 expression is normally low and serum levels are usually nondetectable in the absence of inflammation. With advancing age, however, serum levels become detectable and it is proposed that this reflects an age-associated loss in the normal regulation of gene expression for this molecule. There is also speculation that IL-6 may contribute to the pathogenesis of several diseases that are common in late-life including lymphoma, osteoporosis, and Alzheimer's disease. In this report we demonstrate that plasma levels of IL-6 rise with advancing age in well-selected healthy elderly people and comparably in old rhesus monkeys. That this change reflects a primary aging process is suggested by our findings in C57BL/6 mice in which the age-associated increase in the in vitro synthesis of IL-6 is largely prevented by life span-extending dietary restriction. PMID- 8218596 TI - Effects of hemorrhage on cytokine gene transcription. AB - Injury and blood loss are often followed by infection and the rapid development of organ system dysfunction, frequently involving mucosal sites, such as the lung and intestine. To examine possible mechanisms contributing to these conditions, we used semiquantitative polymerase chain reactions to determine cytokine mRNA expression among cellular populations isolated from mucosal and systemic anatomic sites of mice at predetermined time points following 30% blood volume hemorrhage with resuscitation 1 hr later. Within 1 hr after hemorrhage, significant increases were observed in mRNA levels for IL-1 alpha, IL-1 beta, IL-5, and TGF beta in intraparenchymal pulmonary mononuclear cells. The levels of TGF-beta transcripts among alveolar macrophages were increased 1 hr following blood loss, and increase in IL-1 alpha transcripts was found starting 2 hr posthemorrhage. Cells from Peyer's patches showed significant increases in mRNA levels for IL-1 beta, IL-2, IL-5, IL-6, IFN-gamma, and TGF-beta during the 4 hr following hemorrhage. Significant increases in mRNA levels for IL-1 beta, TNF-alpha, and TGF-beta were present within 4 hr of blood loss among cells isolated from mesenteric lymph nodes. The expression of mRNA for most cytokines was not significantly altered in splenocytes or peripheral blood mononuclear cells at any time point following hemorrhage. These experiments demonstrate that blood loss, even if resuscitated, produces significant increases in proinflammatory and immunoregulatory cytokine gene transcription as early as 1 hr following hemorrhage. These posthemorrhage alterations in cytokine mRNA expression were particularly prominent at mucosal sites, suggesting a mechanism for the increased incidence of pulmonary and intestinal involvement in organ system failure following severe blood loss and injury. PMID- 8218597 TI - Release of soluble TNF/LT receptors from a human ovarian tumor cell line (PA-1) by stimulation with cytokines in vitro. AB - We have demonstrated the presence of the 55- and 75-kDa receptor for tumor necrosis factor (TNF) and lymphotoxin (LT) (TNF-R) in serum, and ascites from women with ovarian cancer. The present studies were initiated to begin to examine the possible cellular source of these receptors in women with ovarian cancer. Human ovarian tumor cells (PA-1) were cocultured for 24-48 hr with various levels of recombinant human cytokines (IL-1 beta, IL-4, IFN-gamma) and the supernatants were assayed by ELISA for the soluble forms of each receptor. PA-1 cells spontaneously release the 55-kDa TNF-R and low levels of the 75-kDa TNF-R. The release of both 55- and 75-kDa TNF-R was stimulated when PA-1 cells were cultured with IL-1 beta and IFN-gamma but unaffected by IL-4. The level of 55-kDa TNF-R was elevated slightly over spontaneous release but the level of 75-kDa TNF-R increased dramatically. IFN-gamma was the most potent stimulator of receptor release particularly of the 75-kDa TNF-R. IFN-gamma also induced increased expression of cell membrane TNF-R measured by binding of 125I-labeled TNF. Membrane TNF-Rs which were induced by IFN-gamma were the 75-kDa type, because TNF binding was blocked by anti-75-kDa TNF-R antibody. These data suggest that IFN gamma selectively induced release and expression of 75-kDa TNF-Rs. PMID- 8218599 TI - Clinical and preclinical studies presented at the Keystone Symposium on Arthritis, Related Diseases, and Cytokines. AB - Topics include treatment of multiple sclerosis (MS) with T cell receptor (TCR) peptides, rheumatoid arthritis (RA) with IL-1ra, IL-2 toxin conjugate, or antibodies to TNF, to CD4, or to ICAM-1, sepsis and five other diseases with IL 1ra, and treatment of experimental animal diseases with soluble receptors, IL-12, TGF-beta2, or small molecule antagonists of cytokines. PMID- 8218598 TI - The functional state of the beta cell modulates IL-1 and TNF-induced cytotoxicity. AB - Insulin-dependent diabetes is an autoimmune disease specifically targeting the pancreatic beta cells and several observations, both experimental and clinical, suggest that the interaction of the immune system with the beta cells is in part determined by the functional state of the target cells, increased beta cell activity resulting in augmented immunologic mechanisms and vice versa for suppressed beta cell activity and decreased immune attack. In this study we investigated whether cytokine induced islet cell cytotoxicity in vitro was in part dependent on the functional state of the beta cells. Cytotoxicity of cultured rat islets was induced by IL-1 (100 pg/ml) and TNF (62.5 ng/ml) individually and in combination and beta cell activity was modulated by culturing the islets in media containing 3.3, 5.5, 11, and 20 mmol/liter glucose. Both IL-1 and TNF were cytotoxic when administered individually and the combination of IL-1 and TNF was more cytotoxic than either cytokine alone. Maximum cytotoxicity was observed at 11 mmol/liter glucose with cytotoxicity being reduced at 5.5 mmol/liter glucose and further reduced at 3.3 mmol/liter glucose. Interestingly, the degree of cytotoxicity was lower in 20 mmol/liter glucose compared to 11 mmol/liter. These results firmly establish that islet cytotoxicity of IL-1 and TNF is highly dependent on the functional state of the beta cells. This suggests that during the IDDM disease process as some beta cells are destroyed, the compensatory increased activity of the remaining beta cells may increase their susceptibility to cytokine attack. Furthermore, our observations provide rational support for the use of beta cell rest as intervention therapy for IDDM. PMID- 8218600 TI - Meta-analysis in literature reviews. PMID- 8218601 TI - Effects of cocaine on dopamine receptor gene expression: a study in the postmortem human brain. AB - The effects of chronic cocaine exposure on dopamine D1 and D2 receptor gene expression in the human brain were studied in postmortem samples from chronic cocaine abusing and matched control subjects. Using in situ hybridization of receptor autoradiography to examine messenger ribonucleic acid (RNA) and binding sites, respectively, neither D1 nor D2 receptor expression was found to be changed in the nucleus accumbens, caudate, putamen, or substantia nigra of the cocaine-exposed subjects. Although chronic cocaine exposure can produce alterations in dopaminergic neurotransmission, sustained compensatory changes in dopamine receptor expression do not appear to occur in the human. PMID- 8218602 TI - Significant correlation between 14C-5-HT uptake by and 3H-paroxetine binding to platelets from healthy volunteers. AB - The lack of correlation between 5-HT uptake by platelets and the ability of platelet membrane to bind antidepressant drugs, particularly imipramine, has been reported. However, more recently it has been suggested that 3H-paroxetine could be a better drug with which to study the platelet 5-HT uptake mechanism in disease states. We have therefore compared the ability of platelet-rich plasma (PRP) from normal individuals to take up 5-HT with the ability of platelet membranes to bind paroxetine. A significant correlation was apparent between the Vmax of 14C-5-HT uptake by PRP and the Bmax of 3H-paroxetine binding to platelet membrane from 30 individuals (r = 0.6468, p = 0.0001). Furthermore, this correlation was highly significant in the 20 female (r = 0.7768, p = 0.00006) but not in the 10 male volunteers. There was also a significant association between Vmax and Bmax and the month of blood sampling but this did not totally account for the correlation between Vmax and Bmax. The simultaneous measurement of 5-HT uptake by PRP and paroxetine binding to platelet membranes from both depressed patients and matched controls should be carried out to confirm and extend these findings. PMID- 8218603 TI - Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia. AB - Schizophrenic patients exhibit deficits in the prepulse inhibition of startle, an operational measure of the sensorimotor gating deficits that are theorized to contribute to cognitive disorganization. In rats, the activation of mesolimbic dopamine (DA) disrupts prepulse inhibition, providing a useful model of the similar deficits in sensorimotor gating in schizophrenic patients. Rats reared in isolation exhibit neurochemical and behavioral abnormalities suggestive of hyperactivity in mesolimbic DA systems. In the present studies, rats reared in social groups or in isolation were tested in startle response paradigms using 120 or 105 dB acoustic pulses, some of which were preceded (100 msec) by prepulses that were 2, 4, 8, or 16 dB above the 65 dB background. Isolation-reared animals were hyperreactive only in response to the initial few startle stimuli. The amount of prepulse inhibition was decreased significantly in isolation-reared animals, particularly when midrange 8 dB prepulses were used. A subsequent study replicated the effect of isolation rearing on prepulse inhibition and suggested that the deficit in sensorimotor gating exhibited by isolation-reared animals may be normalized by the administration of the DA antagonist raclopride (0.05 mg/kg). Hence, isolation rearing provides a nonpharmacological way to induce in rats a deficit in sensorimotor gating that is exhibited by schizophrenic patients. PMID- 8218604 TI - The cortisol response to clonidine in acute and remitted depressed men. AB - To assess the relationship between the hypothalamo-pituitary-adrenal (HPA) axis and the noradrenergic system in patients with major depression, 26 normal controls, 32 acutely depressed patients, and 21 patients with remitted depression, all men, were administered intravenous clonidine (2 micrograms/kg) or placebo. Acute, but not remitted, depressed patients had a greater plasma cortisol baseline than did normal controls (t = 2.0, p < 0.03). Only acutely depressed patients had a greater decrease in plasma cortisol in response to clonidine than to placebo (t = 2.5, p < 0.02). Statistically controlling for both diurnal variation and baseline cortisol, acute, but not remitted, depressed patients had a greater decrease in plasma cortisol in response to clonidine than did the controls (analysis of covariance: F[1,35] = 4.26, p < 0.05). These results support a state-dependent noradrenergic-HPA axis regulatory disturbance in depressed patients, suggesting that clonidine inhibits the elevated plasma cortisol in acute depression but not the normal concentrations observed in remitted depression or healthy controls. PMID- 8218605 TI - Antihistone and anti-dsDNA autoantibodies in Alzheimer's disease and vascular dementia. AB - In order to evaluate their prevalence in senile dementias, serum titer of antibodies against histones and double stranded deoxyribonucleic acid (dsDNA) were measured by means of the ELISA test in patients suffering from vascular dementia (VD), presenile Alzheimer's disease (AD), and senile dementia of the Alzheimer's type (SDAT). Only three subjects out of 87 had dsDNA autoantibodies. On the contrary, VD and SDAT showed high titers of antibodies against histones when compared to healthy controls. A significant relationship was also found between antihistone serum titer and degree of dementia in AD. Results were not influenced by gender, age, or duration of illness. Presence of antihistone antibodies in dementias might reflect an alteration of membrane fluidity and integrity with leakage of nuclear immunogens or disturbances of immune functions, as frequently observed in dementia disorders. PMID- 8218606 TI - Quantified electroencephalographic correlates of depression in Alzheimer's disease. AB - While depression is one of the most frequent psychiatric problems among patients with probable Alzheimer's disease (AD), its mechanism is not well known. We performed quantified EEGs in a consecutive series of seven patients with mild dementia and depression, six patients with mild dementia and no depression, eight patients with moderate dementia and depression, and eight patients with moderate dementia and no depression. Regardless of the severity of dementia, depressed patients had a significantly higher percent theta in posterior brain areas. Moreover, depressed patients with mild AD showed a similar theta frequency as non depressed patients with moderate AD. These findings suggest that the presence of depression may contribute to the qEEG changes of AD. PMID- 8218607 TI - Hypothalamic-pituitary-adrenal axis activity and 1-year outcome in depression. AB - The relationships of longitudinal biological measures to longer-term outcome in depressed patients have not been well explored. This study was designed to investigate whether in a sample of depressed patients: (a) symptomatic and functional outcome at 1 year was significantly different in psychotic major depressed (PMD) patients as compared with nonpsychotic major depressed (NPMD) patients and (b) high urinary or plasma cortisol levels at baseline or 1 year were associated with poorer outcomes at 1 year. Forty-two depressed patients (9 psychotic, 33 nonpsychotic) were evaluated at baseline and at 1 year using a battery of clinical ratings and measures of cortisol. A group of normal, healthy control subjects were similarly evaluated at baseline. At 1-year follow-up, PMD patients did not differ from NPMD patients in their Hamilton Depression Rating Scale (HDRS) and Brief Psychiatric Rating Scale scores (BPRS), but PMD patients demonstrated significantly poorer social and occupational functioning. Significant correlations were observed (n = 18) between higher levels of urinary and plasma cortisol at 1 year and poorer social and occupational functioning at 1 year, independent of the degree of residual depression. In contrast, baseline measures of urinary and plasma cortisol did not predict social and occupational functioning at 1 year. PMID- 8218608 TI - Vascular responses to angiotensin II in anorexia nervosa. AB - Anorexia nervosa (AN) patients have a tendency to develop renin-angiotensin aldosterone (RAA) abnormalities caused by abnormal behaviors expressed over long periods of time. Short-term dietary sodium intake is a known modulator of blood pressure response to infused angiotensin II (A II) in normal subjects. Therefore AN patients and normal gender-matched and age-matched controls were studied for vascular responses to exogenous A II. Untreated AN patients needed significantly greater quantities of exogenous A II to raise diastolic blood pressure (DBP) to over 20 mmHg for 30 min compared with controls (12.1 +/- 0.47 versus 7.6 +/- 0.69 ng/kg/min, p < 0.01). The amount of A II required to raise DBP to over 20 mmHg in AN patients in tests before and after completion of treatment (4.2 +/- 0.33 months later) was significantly different (12.1 +/- 0.47 versus 8.1 +/- 0.25 ng/kg/min, p < 0.01). There was no significant difference between AN patients following treatment and controls. Our results indicate that it requires long time before decreased A II responsiveness caused by chronic sodium depletion normalizes in AN patients. PMID- 8218609 TI - Timing of neuroendocrine responses and effect of m-CPP and fenfluramine plasma levels in OCD. AB - The present study assesses the timing of and relationship between neuroendocrine response and metabolite blood levels following the partial serotonin (5-HT) agonist m-CPP and the 5-HT releaser/reuptake blocker fenfluramine. Cortisol levels peaked significantly earlier than did prolactin, m-CPP, fenfluramine, or norfenfluramine blood levels by time-to-peak analysis. This earlier cortisol response to both 5-HT agents raises the possibility that peripheral mechanisms may play a role in cortisol release. Since peak m-CPP level correlated even more closely to peak prolactin rise than did peak fenfluramine, this suggests that prolactin response to oral m-CPP challenge is useful in assessing 5-HT function. PMID- 8218610 TI - Serum antibodies to herpes simplex virus types I and II in depressed patients. PMID- 8218611 TI - Neuroleptic malignant syndrome secondary to droperidol. PMID- 8218612 TI - Possible involvement of selenium transport protein in a subtype of schizophrenia. PMID- 8218613 TI - Modification of the acoustic startle-reflex eyeblink: a tool for investigating early and late attentional processes. AB - The present experiment examined the sensitivity of short and long lead interval startle eyeblink modification to attentional processing. Eighteen college student subjects were presented with a series of intermixed high and low pitched tones and instructed to attend to tones of one pitch and to ignore tones of the other pitch. The majority of the attended and ignored tones served as prepulses for an eyeblink-eliciting burst of white noise presented at lead intervals of 60, 120, 240 and 2000 ms following prepulse onset. Results indicate that both attended and ignored prepulses produce significant startle eyeblink modification: significant blink inhibition at the 60, 120 and 240 ms short lead intervals, and blink facilitation at the 2000 ms long lead interval. In addition, compared with the ignored prepulse, the attended prepulse produced significantly greater blink inhibition at the 120 ms lead interval as well as significantly greater blink facilitation at the 2000 ms lead interval. These results suggest that both short and long lead interval startle eyeblink modification measures may be useful tools for future investigations of the early and later stages of attentional processing. PMID- 8218614 TI - Late visual and auditory ERP components and choice reaction time. AB - Some relations between different late positive ERP components and choice reaction time (RT) were studied. In order to identify the different components we used visual and auditory stimuli, as well as simple and choice reaction tasks, since one of the components is thought to be modality dependent and the other one task dependent. In the paradigm the stimulus modalities were mixed, which was expected to lead to a maximum dissociation of the components after auditory stimuli (Hohnsbein et al. (1991). Electroencephalography and Clinical Neurophysiology, 78, 438-446). The results demonstrated the overlap of two positive waves in choice reaction tasks: a central one (P-SR), and a parietal one (P-CR). The latency of the P-SR varied greatly across modalities, but did not vary with RT, whereas the latency of the P-CR varied strongly with RT. The different overlap of these components on fast and slow trials caused amplitude and latency variations of the "P300" and the positive slow wave. Our results suggest a relation of the P SR with stimulus evaluation (identification), and of the P-CR with response selection (stimulus-response mapping). PMID- 8218615 TI - Covariation of physiological sleep parameters in coronary patients and their relationships to sleep quality. AB - Relationships between the time series of five physiological sleep parameters were examined and related to sleep quality. Twenty-eight male coronary patients participated in the investigation. Recordings were carried out with a mobile device consisting of two Medilog 4-24 recorders and one DMI-recorder assessing five biosignals: EEG, EOG, EMG, ECG and body movements. Relationships between the time series of physiological sleep parameters were obtained by partitioning of covariance. The investigation showed that substantial relationships exist between the time series of the EEG, the number of eye movements and heart rate. Moreover, the time series of body movements showed substantial relationships to the time series of the EMG and heart rate. High correlations between the time series of the EEG and heart rate were related to a better sleep quality. PMID- 8218616 TI - How are tonic and phasic cardiovascular changes related to central motor command? AB - We examined the influence of central motor command on heart rate, respiration, and peripheral vascular activity. Central command was enhanced or reduced using tendon vibration. Muscle tension was held constant permitting the examination of variation in central command. Experiment 1 demonstrated in 13 college-aged males an enhancement of heart rate and vascular responses to an isometric, extensor contraction when vibration of the flexor tendon was added. Experiment 2 asked whether changes in central command interacted with phasic cardiovascular changes such as stimulus-linked anticipatory cardiac deceleration. Twenty college-aged males performed either an isometric flexor or extensor contraction with or without flexor tendon vibration. As expected, vibration enhanced cardiovascular change with extensor contraction more than with flexor contraction. Relative to control contractions, however, the flexor change was not an absolute decrease in cardiovascular change. More importantly, tendon vibration failed to alter phasic cardiovascular changes. Force and central commands for force induce cardiovascular change, but this change seems independent of phasic changes induced by the anticipation and processing of environmental stimuli. PMID- 8218617 TI - Use of impedance cardiography for assessing cardiovascular control in humans: orthostatic and Valsalva tests. AB - The purpose of this paper is to review our experience with impedance cardiography when used to evaluate cardiovascular control mechanisms in humans. We used the Minnesota impedance cardiograph and the Kubicek stroke volume formula, modified by using spot electrodes instead of band electrodes, a constant rho of 135, and careful attention to standardized procedures. With this technique we focused on the changes in cardiovascular variables with postural stress and during the Valsalva maneuver. More complete definition of cardiovascular function can be obtained by the use of this technique. We describe novel cardiovascular data with the use of impedance cardiography in humans. PMID- 8218618 TI - Application of impedance cardiography during exercise. AB - Impedance cardiography has been used over the last 30 years to measure stroke volume on a beat-by-beat basis. Cardiac output has been successfully measured with either upper or lower body exercise during light or moderate workloads. With strenuous exercise, movement artifacts severely limit the acquisition of a quality impedance cardiogram. Advances in computer technology and signal conditioning techniques have created the next generation of impedance cardiograph systems. The purpose of this study was to evaluate such a system, the noninvasive continuous cardiac output monitor (NCCOM3-R7), at rest and during submaximal upright cycle exercise. In addition, the relationships between thoracic impedance (Z(o)), first derivative of the change in thoracic impedance (dZ/dt) and posture were evaluated using the NCCOM3-R7 and the Minnesota impedance cardiograph 304B (MIC). Twenty-eight healthy men and women participated. The Z(o) progressively increased when moving from the supine to seated to standing position with both instruments. However, the NCCOM3-R7 yielded lower Z(o) values and higher dZ/dt values compared with the MIC for all postures. Z(o) and dZ/dt values appear to be dependent upon factors such as posture, gender, electrical current, and characteristics of the instrumentation. Exercise cardiac output values seemed reasonable for most subjects, although population subsets exist where the accuracy must be questioned. The general consensus supported by the impedance literature and reaffirmed by the present observations is that impedance cardiography provides a reasonable estimate of the directional changes in stroke volume and cardiac output during exercise and can be used to monitor changes in thoracic fluid balance. As this technology evolves and is further refined, it will undoubtedly play an increasing role in environmental medicine, exercise stress testing, cardiac rehabilitation, and sports medicine. PMID- 8218619 TI - Consistency of cardiovascular response pattern to caffeine across multiple studies using impedance and nuclear cardiography. AB - This paper illustrates the use of impedance cardiography in an applied research setting to examine some of the pharmacological effects of caffeine on cardiovascular function. A primary advantage of the technique was in providing a noninvasive approach for studying cardiac versus vascular mechanisms underlying blood pressure responses to acute caffeine challenge. Impedance cardiography allowed the quantification of stroke volumes and cardiac output, and the change in these variables over time in a within-subjects design. Systemic vascular resistances were then calculated when impedance data were combined with simultaneously measured blood pressures. Results from four studies are summarized in which caffeine significantly elevated systolic and diastolic blood pressures. Impedance-derived measures indicate that caffeine's pressor response can be attributed to increased systemic vascular resistance rather than to elevated cardiac output. Our findings were consistent across all four studies, and across all protocols within those studies. Furthermore, these response patterns were confirmed by obtaining similar results using nuclear ventriculography. Thus, with respect to the outcome of testing an applied question, impedance-derived findings were found to be reliable and valid when compared with another technique used more commonly in clinical settings. PMID- 8218620 TI - Use of noninvasive bioelectric impedance to predict cardiac output in open heart recovery. AB - Cardiac outputs (CO) measured by bioelectric impedance (Z) and thermodilution (TD) were compared in ten stable, non-ventilated male coronary artery bypass patients (mean age 59 +/- 12 years) in an open heart recovery unit. The measurements were obtained blindly in three sequential body positions (supine, 45 degrees, final supine) using either a calculated value for resistivity (p) (based upon hematocrit with blood sampled at the time of the study) to estimate CO(Z), or assumed values of p = 135.5 omega cm and p = 150 omega cm. The results indicate high correlations between the two measurement methods (range: r = 0.97 to 0.99) in the initial supine position for all resistivity conditions followed by a progressive decline when body position was changed to 45 degrees and supine (range: r = 0.74 to 0.90). The highest overall correlations and closest absolute mean cardiac output values were obtained when p was calculated from actual hematocrit values obtained at the time of the study. Applying a two-way ANOVA to assess the simultaneous effects of method (TD vx. Z) and position change (supine, 45 degrees, supine), no significant main effects or interactions were found when cardiac output values were estimated using the calculated measurement of p. However, significant main effects of method were found when p was assumed to be either 135.5 omega cm (p > or = 0.005) or 150.0 omega cm (p > or = 0.0001), with impedance showing a tendency to overestimate cardiac output. In conclusion, our findings suggest that impedance is a valid method to estimate cardiac output in this subpopulation of patients in open heart recovery provided that p is calculated at the time the study is performed. PMID- 8218621 TI - Signal fidelity requirements for deriving impedance cardiographic measures of cardiac function over a broad heart rate range. AB - Our findings indicate that the impedance cardiogram spectrum extends from DC to 50 Hz. Any amplifier with an upper band limit less than 50 Hz can be expected to produce attenuation and distortion of the impedance cardiogram. This signal attenuation may be systematically enhanced under conditions of high heart rate when a greater proportion of signal energy will be in the upper frequency range of the impedance cardiogram spectrum. Therefore, the present study was designed to assess the influence of amplifier bandwidth on dZ/dtmax, stroke volume, and systolic time intervals (LVET, PEP, QZ, QX). Simultaneously measured delta Z and dZ/dt signals from two impedance cardiographs, with corner frequencies of 120 and 60 Hz for the delta Z and 50 and 15 Hz for dZ/dt channels, were contrasted over a broad range of heart rate (70-150 bpm). In addition to the analog dZ/dt signals obtained from the instruments, the delta Z signals were digitally converted to dZ/dt by off-line digital differentiation with a 50 Hz corner frequency. The results demonstrated that the measurements with the 15 Hz corner frequency, when compared with the 50 Hz corner frequency measurements, systematically attenuated the dZ/dtmax amplitude and stroke volume measurements as heart rate increased. The attenuation of dZ/dtmax and stroke volume ranged from about 13% to 26% as heart rate increased from 70 to 150 bpm. When the upper bandlimit was 50 Hz, the dZ/dt signal had greater resolution of waveform events and produced less prolonged systolic time intervals. The 15 Hz amplifier differentially influenced the B point, Z-peak and X minimum, having no apparent effect on the temporal location of the B point, but delaying the Z-peak about 21.7 ms and the X minimum about 7.4 ms. These findings indicate that impedance cardiographs with insufficient upper bandlimits will differentially influence ICG-derived measurements as heart rate varies. PMID- 8218622 TI - Impedance cardiography: the failure of sternal electrodes to predict changes in stroke volume. AB - A study was conducted on 26 healthy male adults comparing the stroke volume (SV) and cardiac output (CO) measured with green dye and impedance cardiography in supine, sitting and during 50 W bicycle exercise. The impedance voltage pick-up electrodes were modified from the standard band location and placed at the suprasternal notch and 10 cm below. The percentage change of SV going from supine to sitting was -27.2 +/- 7.4% and -16.9 +/- 22% for the dye and impedance values respectively. The percentage change of SV going from sitting to exercise was 20.9 +/- 11.9% and 36.7 +/- 32.9% for the dye and impedance values respectively. The percentage change in SV determined by impedance shows poor correlation (supine to sitting R = 0.16 and sitting to exercise R = 0.42) with dye values. The individual impedance values for a given change in position or exercise showed considerably more variation compared with the dye. Impedance determination of SV using electrodes on the sternum does not appear to be a valid method for SV and CO measurements. PMID- 8218623 TI - Theory of the determination of systolic time intervals by impedance cardiography. AB - It is possible to accurately measure the left ventricular ejection time from the dZ/dt signal of impedance cardiography. The pre-ejection period can be measured from simultaneous recordings of ECG and dZ/dt. The thoracic admittance (reciprocal value of thoracic impedance) is the sum of a constant tissue admittance and a varying blood conductance Gb (reciprocal value of the blood resistance). dZ/dt represents the changes in Gb. The notches of the dZ/dt signal, corresponding to opening and closing of the aortic valve, are due to conductivity changes of blood caused by changes in orientation of erythrocytes; near zero velocity the first derivative with respect to time of these conductivity changes approaches infinity. Therefore, these notches coincide with the actual opening and closing of the valve, although different vessels, including the aorta, contribute to dZ/dt. Comparison of ejection times, simultaneously measured by impedance cardiography and aortic pressure recording, showed excellent agreement for the whole range of measured heart rates (maximum heart rate = 140 beats min 1, n = 70, r = 0.986). PMID- 8218624 TI - Comparative measures of systolic ejection during treadmill exercise by impedance cardiography and Doppler echocardiography. AB - Measurements of systolic ejection dynamics by impedance cardiography were compared with simultaneous Doppler echocardiography in normal subjects and coronary artery disease patients. Patients with chest pain admitted for elective coronary angiography were monitored by simultaneous impedance cardiography and Doppler echocardiography before, during, and after treadmill exercise. Ensemble averaged ECG, impedance cardiogram (ICG), the first derivative of ICG (dZ/dt), and Doppler waveforms were analyzed to identify systolic ejection variables. The timing of aortic valve opening was well correlated (r = 0.78) the timing of peak ejection velocity was very well correlated (r = 0.86), and the timing of aortic valve closure was moderately correlated (r = 0.69 and r = 0.73) in these subjects. The thoracic electrical impedance acceleration and normalized impedance acceleration indices were moderately correlated with Doppler model acceleration (r = 0.74, r = 0.79). The impedance cardiogram waveforms are of complex origin and are related to both aortic blood velocity and aortic blood acceleration. Users of dZ/dt timing features for determining aortic valvular events might consider alternative impedance features to improve ejection time accuracy. PMID- 8218625 TI - Stability of cardiac impedance measures: aortic opening (B-point) detection and scoring. AB - The accurate assessment of cardiac stroke volume measured by impedance cardiography depends on the reliable measurement of dZ/dtmax and the accurate detection of the relevant points on the impedance cardiogram. In one study, impedance cardiograms were collected for 75 subjects during resting conditions and during four psychologically challenging tasks, in two identical testing sessions. The reliability of stroke volumes calculated from dZ/dtmax measured from the electrical baseline and from the dZ/dt B-point on the waveforms were assessed for the two testing sessions. Consistently higher (but not statistically different) test-retest correlations were observed for the measures calculated using values of dZ/dtmax measured from the B-point. In a second study, dZ/dt waveforms with no B-point reversal from 21 subjects were scored using two alternative B-point detection algorithms: the reversal of the second derivative of delta Z and the peak of the third derivative of delta Z. Both algorithms demonstrated high reliability compared with an expert human operator. The reversal on the second derivative may better locate an inflection point on the dZ/dt signal and the third derivative may provide a good B-point estimation in the absence of any inflection point. PMID- 8218626 TI - Differential patterns of dynamic cardiovascular regulation as a function of task. AB - In cardiovascular reactivity studies, interpretations of the processes supporting the blood pressure response may become problematic when systolic blood pressure, diastolic blood pressure, and heart rate all increase in response to a behavioral challenge. Therefore, in addition to evaluating these cardiovascular responses, this study examined cardiac output, total peripheral resistance and systolic time intervals derived from impedance cardiogram, electrocardiogram and phonocardiogram recordings during a speech stressor, a mirror tracing task, and a foot cold pressor test. All of the behavioral stressors elicited increases in blood pressure and heart rate, with the largest changes occurring during the overt speech. Based on the examination of the response patterns of the underlying hemodynamic variables it would appear that, in both men and women, the blood pressure increase during the speech preparation period was supported by increased cardiac output; the speech itself resulted in a mixed pattern of increased cardiac output and total peripheral resistance; whereas, the mirror tracing and cold pressor tasks produced increased total peripheral resistance. Although men and women produced similar response patterns to the behavioral challenges, sex differences in the estimates of myocardial contractility were observed during rest. These results provide evidence that different behavioral stressors can produce a distinct yet integrated pattern of responses, whose differences may be revealed, when impedance cardiography is used, to derive sufficient response measures for assessing dynamic cardiovascular processes. PMID- 8218627 TI - Impedance cardiography used to assess patterns of cardiovascular response to behavioral stressors. AB - This paper presents two examples of how impedance cardiography may be used to interpret the hemodynamic influences on blood pressures measured during behavioral stress. In Study 1, blood pressure changes which were similar during two tasks were shown to have important differences in their cardiac output and vascular resistance components. During work on a reaction time task having aversive incentives compared with a neutral task, the blood pressure changes were seen to be associated with lowered vascular resistance and raised cardiac activity, a "fight-flight" pattern. In Study 2, blood pressure response differences between two subject groups working on an identical task were found to have blood pressure changes differing in their underlying cardiac and vascular components as measured by impedance. Such uses impedance cardiography have widespread potential application in psychophysiological research with humans. PMID- 8218628 TI - Pathologic effect of estradiol on the hypothalamus. AB - Estradiol provides physiological signals to the brain throughout life that are indispensable for the development and regulation of reproductive function. In addition to its multiple physiological actions, we have shown that estradiol is also selectively cytotoxic to beta-endorphin neurons in the hypothalamic arcuate nucleus. The mechanism underlying this neurotoxic action appears to involve the conversion of estradiol to catechol estrogen and subsequent oxidation to o semiquinone free radicals. The estradiol-induced loss of beta-endorphin neurons engenders a compensatory increment in mu opioid binding in the medial preoptic area rendering this region supersensitive to residual beta-endorphin or to other endogenous opioids. The consequent persistent opioid inhibition results in a cascade of neuroendocrine deficits that are ultimately expressed as a chronically attenuated plasma LH pattern to which the ovaries respond by becoming anovulatory and polycystic. This neurotoxic action of estradiol may contribute to a number of reproductive disorders in humans and in animals in which aberrant hypothalamic function is a major component. PMID- 8218629 TI - Embryonic modulation of basic fibroblast growth factor in the rat uterus. AB - Cellular proliferation and differentiation are critical components of uterine remodeling prior to embryonic implantation. Recent studies have shown that the ovarian hormones, estrogen and progesterone, modulate these cellular events through the production of growth factors. Basic fibroblast growth factor (bFGF) has been implicated in the control of cell proliferation, differentiation, and embryonic development. To clarify its role in uterine remodeling, the cellular distribution of bFGF was examined immunohistochemically in the rat uterus during early pregnancy (Days 2-6). Basic FGF localized intracellularly in stromal and epithelial cells and within the extracellular matrix at Days 2 and 3. It was distinctly evident at the apical surface of epithelial cells at Days 4 and 5 of pregnancy. Concurrent with this apical localization, bFGF was present in the uterine luminal fluid, suggesting release of this growth factor from epithelial cells. Embryonic implantation was accompanied by increased intracellular bFGF content in luminal epithelial and decidual cells. However, similar cells outside of the implantation site and in the artificially decidualized uterus did not express analogous bFGF levels, indicating that a unique signal from the embryo triggers bFGF expression. Changes in the cell-specific distribution of bFGF imply a multifunctional role for this growth factor in uterine cell proliferation, differentiation, and embryonic implantation. In addition, the apical release of bFGF from epithelial cells indicates utilization of a novel secretory pathway for bFGF export during early pregnancy. PMID- 8218630 TI - Testicular regression in pinealectomized Syrian hamsters following infusions of melatonin delivered on non-circadian schedules. AB - The aims of this study were to validate the use of a timed infusion protocol for restoring physiologically appropriate rhythms of melatonin in the circulation of pinealectomized hamsters and, using such infusions, to compare the relative importance of the parameters of the nocturnal melatonin signal--frequency, phase, and duration of the interval between signals--in the photoperiodic control of testicular function in male Syrian hamsters. Hamsters were pinealectomized and fitted with a chronic s.c. cannula enabling them to receive timed infusions of melatonin (50 ng/h) or saline vehicle (50 microliters/h). In experiment 1, RIA of serum samples confirmed that s.c. infusions produced a pattern of melatonin in the blood equivalent in amplitude and duration to that observed previously in pineal-intact animals exposed to a short photoperiod. In experiment 2, we investigated the relative importance of the frequency of the melatonin signal and the duration of the interval between signals. Pinealectomized animals that received infusions of saline for 6 wk had large testes and high concentrations of LH in the serum. Animals that received a series of short-day-like infusions of melatonin of 14-h duration, separated by an interval of either 10 h or 6 h, underwent gonadal regression and had low serum concentrations of LH. Animals that received infusions of melatonin of 8-h duration, separated by intervals of 12 h, also exhibited full gonadal collapse. However, animals that received the same 8-h infusions separated by intervals of 8 h (i.e., once every 16 h) did not undergo gonadal regression and their circulating levels of LH remained high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218631 TI - Localization of endothelin receptor messenger ribonucleic acid in the rat ovary and fallopian tube by in situ hybridization. AB - Rat mRNAs encoding two subtypes of the endothelin (ET) receptor (ET(A) and ETB) were studied in the rat ovary and fallopian tube by means of Northern blotting and in situ hybridization. The mRNA transcripts for the endothelin-1-specific type receptor (ET(A)) in pooled RNA from the ovary and fallopian tube were 4.2 and 5.2 kilonucleotides, and that for the nonselective type receptor (ETB) was 4.7 kilonucleotides; these were similar to transcripts for endothelin receptors from other tissues. ET(A) mRNA expression was abundant in the muscle cell layer of the fallopian tube, but low in the ovary. On the other hand, ETB mRNA was abundant in the granulosa cells in the developing follicles, but low in atretic follicles and absent in the fallopian tube. These results demonstrated that the mRNAs for the two subtypes of the rat endothelin receptor have different expression profiles in the ovary and fallopian tube. ETs may mainly affect the granulosa cells in the dominant follicles as well as the muscle cells of the fallopian tube through ETB and ET(A), respectively. PMID- 8218632 TI - Human leukocyte antigen-DR is a differentiation antigen for human granulosa cells. AB - We raised a murine monoclonal antibody, OG-3, which reacts with human granulosa cells. Immunohistologically, OG-3 antigen was weakly expressed on the granulosa cells of some growing and atretic follicles, but not on those of preovulatory follicles. After ovulation, the antigen expression rapidly increased on granulosa cells during corpus luteum formation. The antigen expression on granulosa/large luteal cells decreased in the mid-luteal phase, but increased again in the late luteal phase. In early pregnancy, OG-3 antigen expression on large luteal cells increased after 7 wk of gestation. The OG-3 antigen distribution in various organs resembled that of human leukocyte antigen (HLA) class II molecules. An HLA class II-positive human B cell line (AKIBA) and a murine L-cell transfectant expressing HLA-DR antigen were positive for OG-3 antigen, whereas an HLA-class II negative human T-cell line and L-cell transfectants expressing HLA-DP and DQ antigens were negative. The molecular mass of OG-3 antigen purified from AKIBA cells was 32-35 kDa. The staining profiles in ovaries with anti-HLA-DR or anti HLA-class II antibodies were similar to that with OG-3. These results indicate that OG-3 antigen is identical to HLA-DR, and that HLA-DR is a differentiation antigen for human granulosa cells. PMID- 8218633 TI - Temperature and water conditions mediate the effects of day length on the breeding cycle of a Sahelian rodent, Arvicanthis niloticus. AB - Laboratory studies of variations in testicular activity (testicular weight and plasma testosterone concentration) were carried out on two populations of Arvicanthis niloticus, a Sahelian rodent that displays the particularity of being able to breed in the dry season. The animals were captured during phases of sexual activity or inactivity and were maintained in the laboratory for 50 days under humid conditions (water-rich diet, 90% atmospheric relative humidity) or dry conditions (water-deficit diet, 20% atmosphere relative humidity) and at low temperatures (20-25 degrees C) or high temperatures (30-35 degrees C). The results show that humid conditions or low temperatures stimulate testicular activity in Arvicanthis niloticus whereas dry conditions or high temperatures inhibit breeding. 1) Humid conditions coupled with low temperatures caused the most marked stimulation of testicular activity and maintained sexual activity at its highest level. 2) Humid conditions coupled with high temperatures, or dry conditions coupled with low temperatures, brought about mild sexual activity in animals that were sexually inactive and a regression of testicular weight and plasma testosterone in animals that were sexually active at the beginning of the experiment. In the latter, the results show that testicular activity was maintained and animals remained capable of breeding. 3) High temperatures and dry conditions inhibited short-day gonadal stimulation. On the other hand, in animals maintained under humid conditions or at low temperatures, gonadal stimulation occurred only under a short photoperiod.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218634 TI - Lysogenic activity of enhancer caltrin and the influence of phospholipids on its expression. AB - Enhancer caltrin permeabilizes the plasma membrane of bovine epididymal spermatozoa as indicated by the release of hyaluronidase from the acrosome and lactate dehydrogenase (LDH) from the sperm cytosol. A previously reported increased calcium uptake by the sperm in the presence of enhancer caltrin was apparently due, in part, to calcium entry into the mitochondria, which had become accessible to external calcium. At 37 microM (200 micrograms/ml), enhancer caltrin released about 30% of the total hyaluronidase in the acrosome and 50% of the cytosolic LDH from epididymal sperm (4 x 10(7)/ml). This event was prevented by phosphatidylserine (PS), presumably through caltrin-phospholipid complex formation, whereas phosphatidylcholine (PC) was ineffective. Cardiolipin induced the release of LDH and this too was prevented by enhancer caltrin. Lysophosphatidylserine (LPS), on the other hand, potentiated the lysogenic activity of enhancer caltrin, promoting the release of the full complement of hyaluronidase and LDH even at a molar ratio of only 1:1 with caltrin. The effect of mixtures of LPS and PS on the lysogenic property of enhancer caltrin was investigated, and it was found that PS suppressed the potentiating effect of LPS. Release of hyaluronidase and LDH took place only when the LPS/PS molar ratio was greater than 2. The implications of these findings for the role of caltrin in mammalian fertilization are discussed. PMID- 8218635 TI - Rapid accumulation of deleted mitochondrial deoxyribonucleic acid in postmenopausal ovaries. AB - To study the aging process in human ovary, we analyzed the accumulation of mitochondrial DNA (mtDNA) mutation in ovary in women of various ages. Thirty-nine tissues from ovaries and abdominal muscles, ranging from those of a fetus to those of a 77-yr-old woman, were collected at artificial abortion or gynecological surgery. Total DNA was extracted from these tissues, and parts of mtDNA were amplified via polymerase chain reaction. Through these experiments, we found a 4977-bp deletion of mtDNA between the ATPase8 and ND5 genes in ovarian samples obtained from menopausal and postmenopausal women and in all muscle samples. Quantitative analysis of the deleted mtDNA also showed that the accumulation of deleted mtDNA in the ovary occurs rapidly around the menopausal period while the accumulation found in abdominal muscle occurs gradually with aging. These results indicated that the mtDNA deletion occurs in muscular tissues even at very young ages but that accumulation of the deletion in ovarian tissue starts at the menopausal period and may have a relationship to dysfunction of the ovary in aging. PMID- 8218636 TI - Chorionic gonadotropin, estradiol, and progesterone levels in baboons (Papio anubis) during early pregnancy and spontaneous abortion. AB - The purpose of this study was to sequentially characterize peripheral chorionic gonadotropin (CG), estradiol (E2), and progesterone (P) profiles during early pregnancy in the baboon (Papio anubis). Ten pregnant baboons were bled sequentially at eighteen time points between Days 8 and 128 of gestation. In addition, blood was obtained at corresponding time points from 5 spontaneously aborting baboons. CG levels were assessed in a mouse Leydig cell bioassay using rhesus pituitary LH as the standard E2 and P levels were measured by RIA. Pregnancy-associated CG activity was detectable by Day 15 (901.4 +/- 275.6 ng/ml), peaked at Day 27 (53,494.1 +/- 14,995.6 ng/ml), and then returned to baseline values by Day 51 (45.4 +/- 8.9 ng/ml). Mean E2 concentrations rose from 28.9 +/- 4.3 pg/ml on Day 8 to 280.6 +/- 145.5 pg/ml on Day 58 and then increased 9-fold to a level of 2436.4 +/- 928.0 pg/ml on Day 72. Mean E2 concentrations ranged between 2065.9 and 3830.9 pg/ml from Day 72 through Day 128. Mean P concentrations ranged from 7.5 to 10.2 ng/ml between Days 8 and 21, rising dramatically to 38.6 +/- 4.6 ng/ml on Day 37 prior to declining to levels that ranged from 11.1 to 17.1 ng/ml between Days 51 and 128. CG levels were low in 3 of 5 animals prior to spontaneous abortion E2 and P concentrations preceding spontaneous abortion were similar to values in uncomplicated pregnancy; however, at the time abortion was detected P concentrations in all 5 animals were 1.3 ng/ml or less.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218637 TI - Hemiorchidectomy leads to dramatic and immediate alterations in pituitary follicle-stimulating hormone secretion and the functional activity of the remaining testis in the adult male bonnet monkey (Macaca radiata). AB - The aim of the present study was to examine the effect of hemiorchidectomy (HO) on serum FSH, LH, testosterone (T), and inhibin (INH) concentrations as well as on the testicular volume (TV) and on changes in the kinetics of germ cell turnovers in the remaining testis of adult male bonnet monkeys. Blood samples collected at 2200 h at various times before and after HO and testicular biopsies obtained at different periods were subjected to hormone analysis and DNA flow cytometry. Though serum T levels were lowered (p < 0.05) at 12 h after HO, T levels rapidly returned to intact control concentrations by Day 5. While serum LH remained unaltered, serum FSH increased markedly within 2 days of HO and remained significantly (p < 0.05) elevated over the next 90 days. Though serum INH showed a significant decrease (p < 0.05) by 15 min of HO, it returned to approximately 80% of intact levels within one week. The TV of the remaining testis showed maximal increment by Day 30 (p < 0.05) of HO. DNA flow cytometric analysis 24 days after HO showed increases (p < 0.05) in spermatogonia (2C) and primary spermatocytes (4C). These cell types by Day 45 had transformed to round (1C) and elongate (HC) (by 38%, p < 0.001) spermatids. Overall spermatogenesis (conversion of 2C to 1C and HC) showed significant enhancement at Days 110 and 175, suggesting that the spurt in spermatogenic activity is not confined to a single spermatogenic cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218638 TI - Serum concentrations of immunoactive and bioactive luteinizing hormone (LH) in gilts. I. Biopotency of LH increases during prepubertal development. AB - The patterns of secretion of bioactive and immunoactive LH during prepubertal development were examined in four groups of 12 gilts each at approximately 3, 4, 5, and 6 mo of age. The rat interstitial cell testosterone assay was validated for the determination of bioactive LH (BLH) in porcine serum. Serum concentrations of immunoactive LH (ILH) were determined by RIA. Blood samples were collected via indwelling jugular catheters every 20 min for a 6-h period of spontaneous secretion. GnRH (0.5 microgram/kg BW) was injected i.v. and blood samples were taken for an additional 4 h at 20-min intervals. Mean serum and baseline concentrations of ILH and of BLH were greater (p < 0.05) in 3-mo-old gilts than in gilts of other ages. Three-month-old gilts also secreted more ILH and more BLH in response to GnRH than 6-mo-old gilts (p < 0.05), but the biopotency of GnRH-induced LH was reduced (p < 0.05) in 3-mo-old gilts. Elevated serum concentrations of ILH and of BLH in 3-mo-old gilts may be inherently necessary to give follicles the maximum opportunity to respond to LH. During the period of prepubertal development, estimates of ILH accurately reflected BLH concentrations except when LH release was stimulated by exogenous GnRH. The age related increase observed in the biopotency of LH released in response to GnRH may reflect a maturational process whereby the biopotency of LH increases as gilts approach puberty. PMID- 8218639 TI - Serum concentrations of immunoactive and bioactive luteinizing hormone (LH) in gilts. II. Biopotency of LH increases at puberty but remains constant throughout the estrous cycle. AB - To determine serum concentrations of immunoactive (I) and bioactive (B) LH during the pubertal surge of LH release, two groups of twelve prepubertal gilts were relocated and exposed to boars to stimulate the onset of puberty. Puberty was defined as the first sign of behavioral estrus and occurrence of a preovulatory surge of LH. Blood samples were taken every 2 h, beginning on the third or fifth day after boar exposure; sampling was continued for 24 h after each gilt had exhibited estrus, or for 7 days, or until two-thirds of the gilts in a group attained puberty. Fifty percent of the total number of gilts exposed to boars attained puberty within 7 days of first boar exposure. Total area under the ILH curve was greater (p < 0.01) than area under the BLH curve during the ovulatory rise in LH. A second experiment was conducted to compare serum concentrations of ILH and BLH during the luteal and follicular phases of the estrous cycle. Blood samples were collected every 20 min for a 6-h period of spontaneous secretion; then GnRH was injected and blood samples were collected every 20 min for 4 h from gilts during the luteal (n = 16) and follicular (n = 15) phases, respectively. BLH baseline tended to be greater (p = 0.07) during the follicular phase than during the luteal phase. Mean peak amplitude of naturally occurring peaks of ILH and BLH was greater (p < 0.05) during the luteal phase than during the follicular phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218640 TI - Cryopreservation of mouse oocytes: mutagenic effects in the embryo? AB - We have shown in previous studies that the complete cycle of cryopreservation and prefreezing manipulations increases the degeneration and decreases the fecundability of mouse oocytes. The present study confirms these results. Moreover, we show that the increase of polyploidy previously observed in one-cell zygotes derived from frozen-thawed oocytes persists during the early stages of embryonic development. Furthermore, embryos obtained from frozen oocytes or oocytes exposed to prefreezing manipulations show an increase in the frequency of sister chromatid exchanges. Since the estimation of sister chromatid exchange is a sensitive test of mutagenicity, this suggests that the complete cycle of cryopreservation might alter the oocyte and, more particularly, induce DNA damage. PMID- 8218641 TI - Expression of the Hprt gene during spermatogenesis: implications for sex chromosome inactivation. AB - The goal of this study was to determine the developmental pattern of expression of the X-linked gene for hypoxanthine phosphoribosyltransferase (Hprt) during spermatogenesis and the relevance of this expression to X-chromosome inactivation during meiotic prophase. The results demonstrated that HPRT activity is maintained in mouse spermatogenic cells throughout development in spite of X chromosome inactivation; however, specific activities of HPRT in meiotic and postmeiotic germ cells were significantly lower than in premeiotic ones. Maintenance of Hprt transcripts at all stages was also demonstrated. Interestingly, the highest level of Hprt transcripts was found in leptotene/zygotene spermatocytes, suggesting a hyperactivation of the Hprt gene and/or stabilization of Hprt transcripts in these cells. Hprt transcripts were present at very low levels in pachytene spermatocytes, and at slightly elevated levels in round spermatids. It was also found that the relative abundance of Hprt transcripts in the somatic cells of germ-cell-deficient testes was much greater than that in meiotic and postmeiotic germ cells, even though their activities of HPRT were similar. Examination of the translational status of Hprt transcripts in testicular cells revealed that while most of the transcript was translationally active in somatic cells of testes, less than half of the transcript was on polysomes in pachytene spermatocytes and round spermatids. Since no functional autosomal Hprt gene exists in the mouse, these data suggest that the germ cell maintains both transcript and protein product of the Hprt gene in spite of apparent X-chromosome inactivation. PMID- 8218642 TI - Human recombinant inhibin A suppresses plasma follicle-stimulating hormone to intact levels but has no effect on luteinizing hormone in castrated rams. AB - This study tested the hypothesis that inhibin is a major negative feedback regulator of FSH secretion but has minimal effects on LH secretion in rams. In experiment 1, castrated rams (wethers) were given either vehicle or human recombinant inhibin A (hr-inhibin) as three s.c. or three i.v. 50-micrograms injections 6 h apart or as one 50-micrograms i.v. injection followed by 100 micrograms infusion over 12 h. Human recombinant inhibin suppressed plasma FSH while the vehicle had no effect. The greatest suppression in plasma FSH was achieved following i.v. administration of hr-inhibin given either by repeated injection or by infusion. In experiment 2, wethers were given vehicle or a 50 micrograms i.v. injection followed by 800-micrograms infusion of hr-inhibin over 12 h. Infusion of hr-inhibin suppressed plasma FSH with a maximal suppression of 53.3% occurring between 15 and 24 h after the start of treatment. During this period, the plasma concentrations of FSH and inhibin were in the range of values for intact rams. Human recombinant inhibin did not influence plasma LH in either experiment. This study demonstrated that physiological treatment with inhibin, in the absence of testosterone, has the capacity to suppress plasma concentrations of FSH in wethers to the levels found in intact rams. PMID- 8218643 TI - Development of ovine embryos co-cultured on oviductal cells, embryonic fibroblasts, or STO cell monolayers. AB - One- and two-cell ovine embryos were co-cultured on primary monolayer cultures of ovine oviductal cells (OM) and ovine embryonic fibroblasts (EF) or on monolayers of STO cells (STO), a permanent cell line, to determine whether a co-culture system could be developed for ovine embryos utilizing a well-characterized cell line. More than 65% (n = 64) of embryos co-cultured on OM and STO for 5 days cleaved beyond the "in vitro" block whereas only 26% (n = 35) of embryos co cultured on EF cleaved to the same degree (p < 0.05). Mitotic inactivation of the monolayer did not alter the response to each cell type. In a second experiment, development of embryos was similar after co-culture on OM or STO cells for both 3 and 6 days. Co-culture of zygotes on OM and STO cells produced 38 and 33% blastocysts after 6 days of co-culture. After embryo transfer, only recipients receiving at least one blastocyst became pregnant. About 33% of the transferred blastocysts produced fetuses. STO cell co-culture may provide the same stimulus to development as OM cell co-culture and may be advantageous for study of the requirements for early ovine embryonic development. In addition, STO cells displayed contact inhibition and formed monolayers that did not overgrow embryos as did primary cultures of ovine oviductal cells. PMID- 8218644 TI - Embryo-dependent induction of uterine receptivity assessed by an in vitro model of implantation in mice. AB - To investigate the molecular basis of initial interactions between the trophoblast and the uterine epithelium at implantation, we developed an in vitro model for implantation in mice using primary uterine organ cultures as the substrate. In this model, embryos attached to the endometrial explants within 60 min. We were able to observe the attachment between embryos and endometrial explants in real time. Using this model, we investigated the attachment of embryos to uterine strips cultured from pregnant mice, pseudopregnant mice, pseudopregnant mice that had received hCG injections, and pregnant mice whose utero-tubal junctions had been ligated on Day 2 of pregnancy. The serum levels of progesterone in pregnant and pseudopregnant mice were also compared. The percentages of embryos that attached to uterine strips cultured from pregnant mice on Days 1-4 were low (0.0-15.0%). However, by Days 5-7, percentages of attachment increased markedly (66.8-74.8%). These levels were significantly higher than those observed for pseudopregnant mice (0.0-18.0%) and pseudopregnant mice that had received hCG injections (0.0-15.0%). The percentages of attachment to the ligated horns of pregnant Day 5 uteri (58.3-61.5%) were significantly higher than that of pseudopregnant mice (10.0%). The percentages of attachment to the ligated horns of pregnant Day 6 and 7 uteri decreased significantly (3.2% 19.4%). On the other hand, the percentages of attachment to the unligated horns of pregnant Day 6 and 7 mouse uteri did not decrease significantly (61.1-70.0%). The serum progesterone levels of pseudopregnant mice were not significantly lower than those of pregnant mice on Days 1-5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218645 TI - Uterine kallikrein in the early pregnant rat. AB - Uterine homogenates of cycling and early pregnant Sprague Dawley rats and purified rat urinary kallikrein showed similar curves of displacement of 125I kallikrein binding to a polyclonal antibody. Uterine kallikrein concentration measured by RIA was 8.7 +/- 2 SEM ng/g wet weight during the cycle (n = 6 in diestrus and metestrus) and 20.8 +/- 2 SEM (n = 7) ng/g wet weight on Day 7 of pregnancy (P7) (p < 0.001). On P7, kallikrein concentration was increased 12.4 fold in the implantation nodes, as compared to the interimplantation segments. Uterine homogenates of rats on P7, submitted to DEAE-cellulose chromatography and Sephadex gel filtration, yielded two fractions containing kallikrein immunoreactivity and kininogenase activity, with molecular masses that ranged from 120-125 kDa and 39-43 kDa, respectively. In the RIA, both fractions displayed parallelism with purified kallikrein. Enzymatic activity was expressed after activation by trypsin. It was inhibited by aprotinin, PMSF, p-amino benzamidine, and leupeptin, but not by soybean or ovomucoid trypsin inhibitors. Kallikrein mRNA was demonstrated by reverse transcriptase/polymerase chain reaction in uteri of nonpregnant and P7 rats. These results show that rat uterus synthesizes one or more serine proteases that are immunologically and enzymatically related to tissue kallikrein in the implantation node on P7- determined both by an increment of whole uterus kallikrein content and a depletion of the interimplantation segments--suggests that kallikrein may play a role in the vasoactive changes of implantation. PMID- 8218646 TI - Hormonal regulation of endometrial prostaglandin F2 alpha production during the luteal phase of the rhesus monkey. AB - To study the hormonal regulation of prostaglandin (PG) production by the endometrium during the luteal phase of the primate menstrual cycle, the standard artificial menstrual cycle (SAMC) of the rhesus monkey was manipulated (MAMC) such that in one group of monkeys, there was an absence of the mid-cycle peak of estradiol-17 beta (E), but normal luteal phase progesterone (P). In the second group, there was a mid-cycle peak of E, but no luteal phase P. The accumulation of PGF2 alpha in tissue culture medium from explants of endometrium obtained on cycle Day 14 or 23 of the MAMC was compared to the accumulation of PGF2 alpha from explants on cycle Day 14 or 23 of the SAMC (expressed as mean ng +/- SEM/mg/24 h). Omission of the mid-cycle E peak in the MAMC did not alter endometrial PGF2 alpha production in vitro on cycle Day 14, compared to the SAMC; whereas, on cycle Day 23 PGF2 alpha, production was reduced (35.1 +/- 6.4 ng/mg/24 h), compared to that in the SAMC (53.8 +/- 10.3 ng/mg/24 h; p = 0.06). Omission of P during the MAMC resulted in higher PGF2 alpha production in vitro on cycle Day 14 (p < 0.01) and lower PGF2 alpha production on cycle Day 23 (p = 0.05), compared to that in the SAMC on these days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218647 TI - Tissue distribution of alpha 1-proteinase inhibitor messenger ribonucleic acid and its regulation by glucocorticoids in fetal and neonatal sheep. AB - alpha 1-Proteinase inhibitor (alpha 1-PI) controls several proteinases that play important roles during inflammation and tissue remodeling, but its function during mammalian development remains obscure. We have therefore studied the ontogeny of alpha 1-PI mRNA in selected fetal and newborn sheep tissues by Northern blotting. Furthermore, because glucocorticoids play important roles in fetal maturation and parturition in sheep, we measured the relative amounts of glucocorticoid receptor (GR) mRNA in the same tissues and compared the effect of dexamethasone (DEX) administration on alpha 1-PI mRNA levels in liver and kidney of fetal and adult sheep. In the ontogeny study, a 1.8-kb alpha 1-PI mRNA was found in fetal adrenal gland and lung at Days 60-70 but was low or undetectable in these tissues at later gestational ages. By contrast, the abundance of hepatic alpha 1-PI mRNA did not vary between Days 60 and 130 of gestation, but decreased significantly (p < 0.05) at term (Days 145-147) and in newborn lambs. In the fetal kidney, it was also present between Days 60 and 130, and its relative abundance increased significantly (p < 0.05) in term and newborn lambs. These changes did not correlate with GR mRNA abundance, which was relatively stable in all tissues except the kidney, where a significant (p < 0.05) decrease was observed in neonates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218648 TI - Preimplantation endocrinology in the Djungarian hamster (Phodopus campbelli): progesterone, estrogen, corpora lutea, and embryonic development. G. AB - This study reports the results of a detailed investigation of pregnancy in the Djungarian hamster, Phodopus campbelli, with a 2-h time resolution from 2000 h on proestrus (Day 0) through 0600 h on Day 5. Comparisons of the serum levels of progesterone (P4) and estradiol-17 beta (E2), along with the extractable content of each in the corpora lutea and the nonluteal portion of the right ovary, were used to assess the sources and circulating levels of these steroids throughout preimplantation pregnancy. Simultaneous investigation of embryonic development and location within the reproductive tract permitted accurate staging of development. The time course for development and implantation was similar to that in other short-cycle rodents, with transit into the uterus on the evening of Day 3 and implantation beginning early on Day 5 of pregnancy. In three different circumstances, tissue accumulations of steroids were not associated with concurrent increases in serum levels. The first, late on proestrus to early Day 1 of pregnancy, was a significant accumulation of P4 in the nonluteal ovary while serum levels remained basal. The second, throughout Day 2 of pregnancy, was an accumulation of P4 in the corpora lutea that paralleled the pattern of serum P4 during a normal estrous cycle, but which, in these pregnant females, was not seen as elevated serum P4 levels. This response is likely to be coitally induced and thus advances the first maternal steroid response to pregnancy by 24 h relative to other short-cycle rodents studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218649 TI - Influence of food restriction on neuropeptide-Y, proopiomelanocortin, and luteinizing hormone-releasing hormone gene expression in sheep hypothalami. AB - Chronic food restriction decreases secretion of LH as a result of inhibitory influences on secretion of LHRH. We have previously reported that neuropeptide-Y (NPY) may directly or indirectly mediate this inhibitory effect on LHRH secretion. In the study reported here, we tested the hypothesis that long-term food restriction suppresses tonic release of LH as a result of 1) an increase in biosynthetic activity of NPY neurons in the arcuate nucleus of the hypothalamus, 2) an increase in activity of neurons that secrete beta-endorphin, and 3) a decrease in biosynthesis of LHRH. To test predictions of the hypothesis, we compared levels of mRNA encoding NPY, proopiomelanocortin (POMC; the precursor peptide of beta-endorphin), and LHRH, as well as tonic secretion of LH in food restricted and well-nourished ewe lambs. Ten ewe lambs were ovariectomized at 18 wk of age and randomly assigned to receive either 100% nutritional requirements (FED; n = 5), or 30% requirements (R; n = 5) between 18 and 25 wk of age. At 25 wk of age, blood samples were taken every 10 min for 6 h and assayed for LH. The tonic release of LH in R lambs was less than that of FED lambs. Hypothalami were collected 4 days after blood sampling and sectioned at 12 microns for use in in situ hybridization. Radiolabeled molecular probes specific for mRNAs encoding NPY, POMC, or LHRH were hybridized to hypothalamic tissue sections. Levels of NPY mRNA were 88% greater in R vs. FED lambs (p < 0.01), whereas levels of POMC mRNA were 52% lower in R vs. FED lambs (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218650 TI - Cadmium in vivo causes disruption of tight junction-associated microfilaments in rat Sertoli cells. AB - Ten-week-old male Sprague-Dawley rats were injected i.p. with cadmium chloride solution in a single dose of 0 or 1.0 mg/kg BW. At 4, 24, 48, and 72 h after injection, testes of the animals were collected, detunicated, and fixed in 10% formalin. Individual seminiferous tubules were isolated and the stages of the cycle of the seminiferous epithelium were determined through use of transillumination under a stereomicroscope. The tubules were stained with rhodamine-phalloidin, mounted on glass slides, and examined via a confocal microscope. This cadmium dose did not cause visible vascular lesion in the testes. The cadmium treatment resulted in changes in the pattern produced by microfilaments in the basal region of Sertoli cells. The observed change in basal Sertoli cell microfilaments consisted of fragmentation of the microfilament bundles as compared to those in seminiferous tubules from control animals. This apparent lesion was first observed in stages VIII through XI at 24 h after the cadmium exposure. As the time after exposure increased, the lesion within a stage occurred with increasing severity, and later stages of the cycle of the seminiferous epithelium were also affected. At 48 h after exposure, disorganization of microfilament bundles was seen in stages VIII through XIII/XIV. At 72 h after exposure, severe fragmentation of microfilament bundles was observed from stage VIII through stages II/III. The microfilament bundles in several stages prior to stage VIII remained unaffected. No change was observed in the microfilaments of peritubular cells. At 4 h after exposure, testes showed no change in the organization of microfilament bundles at the basal region of Sertoli cells or microfilaments in the peritubular cells. We conclude that a single cadmium chloride dose of 1 mg/kg results in the disruption of basal Sertoli cell microfilament bundles in the rat seminiferous epithelium, and that the action of cadmium is cell-specific and stage-specific. PMID- 8218651 TI - Expression of cytokines in placentas of mice undergoing immunologically mediated spontaneous fetal resorptions. AB - It is clear that the immune system and the reproductive system interact with and influence each other and that the immune system can have positive and negative regulatory effects on the outcome of pregnancy. The discovery of murine models of immunologically mediated spontaneous fetal resorptions has proved to be very useful for the study of immunological influences on pregnancy. In an attempt to elucidate the mechanisms underlying pregnancy impairment in one such "natural" model of pregnancy loss, we compared the expression of the cytokines tumor necrosis factor alpha, interferon tau, and interleukin-2 in placental tissue from a resorption-prone strain combination with the expression from a normal combination. We found significantly enhanced expression of these three cytokines in placentas from the resorption-prone combination using dot-blot hybridization and Northern hybridizations. Since these cytokines are abortifacients in vivo and have detrimental effects on the placenta, and hence on fetal development and survival, our demonstration of enhanced expression of these deleterious cytokines may give insight into the mechanisms involved in immunologically mediated spontaneous abortions. PMID- 8218652 TI - Melatonin secretion and puberty in female lambs exposed to environmental electric and magnetic fields. AB - This study determined whether chronic exposure of female lambs to the electric and magnetic fields (EMF) of a high voltage transmission line can alter pineal secretion of melatonin and the normal occurrence of puberty. Twenty female Suffolk lambs were assigned randomly in equal numbers to a control and a treatment group. Treatment from 2 to 10 mo of age consisted of continuous exposure within the electrical environment of a 500-kV transmission line (mean electric field 6 kV/m, mean magnetic field 40 mG). Treated lambs were penned directly beneath the transmission line; control lambs were maintained in a pen of similar construction 229 m from the line where EMF were at ambient levels (mean electric field < 10 V/m, mean magnetic field < 0.3 mG). Melatonin was analyzed by RIA in serum of blood samples collected at 0.5-3-h intervals over eight 48-h periods. To assess attainment of puberty, serum concentrations of progesterone were determined by RIA from blood samples collected twice weekly beginning at 19 wk of age. Concentrations of circulating melatonin in control and treated lambs were low during daylight hours and increased during nighttime hours. The characteristic pattern of melatonin secretion during nighttime (amplitude, phase, and duration) did not differ between control and treatment groups. Age at puberty and number of subsequent estrous cycles also did not differ between groups. These data suggest that chronic exposure of developing female sheep to 60-Hz environmental EMF does not affect the mechanisms underlying the generation of the circadian pattern of melatonin secretion or the mechanisms involved in the onset of reproductive activity. PMID- 8218653 TI - [Negative identity in young immigrants]. AB - Immigrants experience conflicting values more frequently than "native" citizens. When experienced by immigrants in their teens, clashing values can give rise to feelings of rejection, as well as a negative self-image and image of others; in some cases, these opposing values even lead to family breakups. The identity crisis worsens if the messages conveyed by the social environment are contradictory or incoherent. If these messages present negative aspects, the self image is threatened by being discredited, for example in the case of racist stereotypes and xenophobic reactions. The most dangerous response is the internalization of a discredited image. Youth react aggressively or repress a racist experience by negating it. For some, assimilation goes as far as putting down one's very own community. On the other hand, some will place enormous value on their differences and follow a strategy that can lead to political activism, which is not without its own forms of excess. These various strategies depend on specific factors: cultural traits, political trends, community links. PMID- 8218654 TI - [Therapy with immigrant families]. AB - This article illustrates through clinical examples a number of specific aspects related to work carried out with immigrant families. Topics include the disorganizing effects of immigration, the place of the father and magical thinking in immigrant families. PMID- 8218655 TI - [Transcultural approach to non-francophone patients originating from Southeast Asia in the psychiatric service network of the XIIIth district of Paris]. AB - Following the political upheaval that shook the Indochinese peninsula in the middle of the 1970s, many refugees originating from Southeast Asia re-established themselves in France. Since 1976, many of these refugees have formed a large Asian community in the XIIIth arrondissement of Paris. As a result, the arrondissement's psychiatric services, which cover the entire Asian neighborhood, have been confronted with the arrival of increasing numbers of non francophone patients from this ethnic minority. In this article, the authors present the steps that were taken by the psychiatric services to meet the very particular historical, cultural and psychopathological needs of this population. PMID- 8218656 TI - [Aspects in the psychological development of children from the Maghreb]. AB - Studies on the psychological development of the Maghreb child, from the psychomotor as well as the emotional points of view, are still quite rare, as is literature and research on the Maghreb child's family and environment. This article synthesizes various data, while identifying what is generally unknown or misunderstood about the Maghreb. This is namely the case of information surrounding the Islam faith. Also, by raising questions about the female child, the author examines one of today's major sociocultural and political problems in Islamic countries: the female citizen of tomorrow in a changing world--an issue which the author considers essential to any endeavour in the field of mental health. PMID- 8218657 TI - [Police-ethnic minority relations]. AB - In this testimony, the author presents a critical analysis of relations between the police and black minorities in particular. The author explores the underlying mechanisms and the origins of the deterioration of these relations, and suggests measures to change the respective perceptions and attitudes, and to create a positive climate leading to mutual trust. PMID- 8218658 TI - [The integration process of refugees, a major explanatory factor during intervention]. AB - In light of scientific literature produced over the last ten years, it appears that health and social work professionals should, when dealing with people belonging to minority cultures, go beyond the purely interpersonal approach to problems. Rather, they should lend an ear to the different notions of life and society, and adjust their intervention patterns to the integration conditions of immigrants. The special situation of refugees requires a special approach based on the knowledge of their pre-migrant conditions, as well as on the establishment of closer ties between welcoming institutions and these migrant families. PMID- 8218659 TI - [Youth from cultural communities]. AB - In Quebec, young immigrants must adapt themselves at the same time as their families to the changes imposed by a society which is itself experiencing problems related to minorities and language conflicts. Parents, which have high hopes for their young, are torn between their own values and those of the new nation. Because immigrants families, especially mothers, have a poor understanding of the language, as well as the educational and social services, it is difficult for them to avoid being labelled in the academic and legal worlds. Discipline is often at the centre of problems with teens. The conflict between generations takes on special meaning, as youth are able to adapt faster and easier to the new society's culture. Nevertheless, placing value on cultural origins can help youth challenge racism and rejection. The author believes that more effort should be invested in information services for parents, as well as in schools and their cultural and pedagogical adaptation measures. PMID- 8218660 TI - [Psychiatric emergencies in the context of community mental health services]. AB - Psychiatric services dispensed according to geographic sectors has been a reality of the Montreal area psychiatric care system for about fifteen years. In a dense urban environment where the territorial limits of sectors do not necessarily follow the borders of residential areas, divisions by sector can create serious access problems. On a different note, when the distribution of mental health services is patterned after the main urban arteries, sectorialization becomes the validation of an existing situation, its success thereby ensured by the force of circumstances. In this article, the access to emergency psychiatric services over the sectorialized territory of Ile Jesus is examined based on archival data provided by Sacre-Coeur and Cite de la Sante hospitals. The data reveal that patients with a psychiatric ailment present themselves to the emergency ward of the hospital of their sector. These patients of emergency services are characterized by usage patterns that are no different from those of users of all types of health care services, psychiatric or not, regardless of the reason of the visit. However, the place of use of sectorialized psychiatric services has a halo effect on non-sectorialized psychiatric services. The impact of sectorialization on the usage and access of services is therefore a complex phenomenon. PMID- 8218661 TI - [Acculturation, stress and mental health in Lebanese immigrants in Montreal]. AB - This cross-sectional study examined the effect of immigration and acculturative stress on the mental health of a sample of 197 Lebanese immigrants in Montreal. An Orthogonal Model of Cultural Identification was used to determine whether the acculturation style adopted by immigrants had any effect on mental health or on acculturative stress. Results revealed no significant differences in psychological distress between the Lebanese sample and a comparative group of Quebec native-born. Among the indices of acculturative stress, adaptation problems alone predicted psychological distress. Finally, acculturation styles did not have any effect on psychological distress or on acculturative stress indices, with discrimination excepted. Individuals who adopted the Assimilation style reported less discrimination than those in the Ethnocentric and Integration groups. Results are discussed with reference to findings reported in the literature on Canadian studies. PMID- 8218662 TI - [Intervention in mental health: an unexpected function of shelters for homeless women]. AB - The development of services for the homeless is today the target of widespread criticism. Institutions are tending to duplicate services to ensure their survival, which brings about the risk of creating second-rate services for this area of the population. In addition, many critics fear that, because of policies established by institutions, services for the homeless tend to foster rather than fight transience. Based on an analysis of the evolution of mandates of shelters for homeless women, the author suggests that the development of services for the homeless has been influenced by factors other than the survival instinct of these organizations. PMID- 8218663 TI - [Concepts and attitudes of parents of adolescents in regard to suicide]. AB - In the context of parents reacting with surprise to the suicidal tendencies of their teenage child, the authors prepared a questionnaire for 380 parents of adolescents to gauge the realism of their perceptions on the topic. The authors noted differences of opinion between fathers and mothers among parents who have experienced a variety of situations related to suicide and others who have received information on the matter. These differing points of view concern the impulsive nature of the gesture, the age of the suicidal person, the opportunity to intervene and the level of acceptance of suicide. In addition, this study underscores the importance of implementing prevention programs that go beyond the simple distribution of information. PMID- 8218664 TI - [Experiences and perception of clients of a crisis center]. AB - The article presents the results of a series of semi-directed interviews conducted with fifty former clients of a crisis centre. Collected data relate to the experiences of residents and their appreciation of services supplied, to the social workers and to results of intervention carried out by the centre. PMID- 8218665 TI - [Mental health and trans-culture: a missed appointment?]. PMID- 8218666 TI - [Culture and mental illness among the Inuit of Nunavik]. AB - While the major psychiatric disorders described in current nosology can be found among the Inuit of Northern Quebec (Nunavik), there are important cultural influences on the symptomatology, social response and course of these disorders. A literature review, consideration of experiences with psychiatric consultation among the Inuit and the preliminary results of ongoing ethnographic research underscore the importance of the study of Inuit ethnopsychology and current attitudes toward the mentally ill in developing culturally sensitive psychiatric care. PMID- 8218668 TI - [Fascination with and flight in the other]. PMID- 8218667 TI - [The intercultural approach in the support process]. AB - This study is the outcome of research carried out on a migrant group in France, of training experience with social work and psychology professionals dealing with migrant communities and of research focused on these training experiences (Cohen Emerique, 1984, 1986; Malewaska-Peyre, 1988). It is the result of many experiences in the worlds of theory and of practice, all of which revolve around the interaction between migrant populations and the agents responsible for their integration in France, namely social workers, psychologists, paramedical personnel, teachers and training professionals. Interaction here is defined as an exchange process which, through communication, ensures reciprocity. PMID- 8218669 TI - ["Grey feathers"--encounter with aged Algonquins from Kitigan Zibi]. AB - The author explores the symbolic efficiency of strangeness she experienced when meeting those people whom, as a child, she learned to consider as the strangest of strangers: the American Indians. The author identifies three signifiers on which Algonquins build their individual and collective identities: the patronymic, the accomplishments of the elders and the earth. These three signifiers were key to developing ties that connect the present with the past, while still emphasizing the differences that ensure cultural symbolism and, therefore, their distinction from the White man's world. PMID- 8218670 TI - Infective endocarditis. AB - As compared to the characterization of IE in the 1970s and early 1980s, it appears that IE in the 1990s is more likely to present acutely and in association with fewer classic stigmata and is more likely to be caused by S. aureus. Whether this represents a true clinical and microbiological shift in disease spectrum or is the result of reporting bias is unclear at this time. The ability to clinically designate a case definitely as IE has been improved with utilization of new diagnostic criteria that incorporate findings from two-dimensional echocardiography in the classification schema. These new criteria have been validated in selected patient populations but remain to be validated in other patient groups at risk for IE (e.g., prosthetic-valve recipients). Two dimensional echocardiography is the noninvasive technique of choice for defining vegetative IE. TEE is significantly more sensitive in identifying valvular vegetations than is TTE, and TEE also is the method of choice for delineating periannular complications of IE. The role of Doppler flow assessment of valvular regurgitation in IE remains to be clarified. Short-course (2-week) regimens of beta-lactam agents plus aminoglycosides appear to be highly effective for the treatment of right-sided IE due to S. aureus. The use of vancomycin for treatment of S. aureus IE remains problematic because of reports of slow response and suboptimal treatment outcomes. PMID- 8218671 TI - Trimethoprim-sulfamethoxazole prophylaxis in granulocytopenic patients with acute leukemia: evaluation of serum antibiotic levels in a randomized, double-blind, placebo-controlled Department of Veterans Affairs Cooperative Study. AB - Despite widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for prophylaxis in neutropenic patients, questions remain regarding its efficacy, toxicity, the risk of selection of resistant isolates, and the relation of its activity to selective decolonization vs. the attainment of direct inhibitory levels within blood and tissues. We evaluated the effect of TMP-SMZ (160/800 mg orally every 12 hours) in 42 adult granulocytopenic patients (< 100 absolute neutrophils/mm3, mean duration 13.3 days) undergoing chemotherapy for acute leukemia at 11 participating Veterans Administration Medical Centers in a randomized, double blind, placebo-controlled trial. No significant differences in survival, frequency of bacteremia, overall infections, use of systemic antimicrobial therapy, or adverse effects, including myelosuppression, were observed between patients receiving TMP-SMZ vs. those receiving placebo. All patients acquired trimethoprim-resistant organisms. Concentrations of trimethoprim in serum were significantly lower before febrile episodes than when patients were afebrile. These results suggest that the purported activity of TMP-SMZ may be related to the serum concentration achieved. Moreover, the results highlight the need for additional study of the value of antibiotic prophylaxis in neutropenic patients. PMID- 8218672 TI - Antibacterial chemoprophylaxis in neutropenic patients--where do we go from here? PMID- 8218673 TI - Rapid diagnosis of Chlamydia psittaci pneumonia. AB - Two cases of Chlamydia psittaci pneumonia are presented. In each, a rapid diagnosis was made through the use of direct immunofluorescent antibody staining of respiratory secretions with monoclonal antibodies to chlamydial antigens. In one case the diagnosis was confirmed by the isolation of the causative organism from sputum and a pharyngeal swab. Chlamydial lipopolysaccharide was detectable in sputum from this patient in an enzyme immunoassay. Serological responses to C. psittaci, Chlamydia trachomatis, and Chlamydia pneumoniae were evaluated, and serological cross-reactivity was observed between each species. Rapid antigen detection systems for Chlamydia species that use commercially available reagents can be helpful in the evaluation of selected patient populations. PMID- 8218675 TI - Screening for schistosomiasis, filariasis, and strongyloidiasis among expatriates returning from the tropics. AB - The clinical utility of eosinophil determinations, stool examinations, and serological studies for detection of parasitic infection was examined in an asymptomatic expatriate population by retrospective chart review. The screened population consisted of 1,605 patients attending a tropical medicine clinic. The sensitivity of eosinophil counts as a screening test for infection with filaria, schistosomes, or Strongyloides stercoralis was 38%, and its positive predictive value was 9%. A cost-efficacy analysis of the use of three diagnostic tests in screening for infection with filaria (n = 23), schistosomes (n = 34), or Strongyloides (n = 7) was performed. The use of stool examination and serological screening together had a sensitivity of 89%, at a total cost similar to that of a conventional strategy involving a stool examination and an eosinophil count, which would have picked up only 61% of our cases. In this population, eosinophil counts contribute little to the diagnostic accuracy obtained with stool examination and serological screening, and the low specificity of eosinophil counts generates high costs. PMID- 8218674 TI - Ulcerative and plaque-like tracheobronchitis due to infection with Aspergillus in patients with AIDS. AB - Tracheobronchitis is an uncommon manifestation of infection due to Aspergillus species, occurring in < 7% of cases of pulmonary aspergillosis. At least 58 cases of invasive aspergillus tracheobronchitis have been described since 1962. We describe four patients with AIDS, all of whom were severely immunocompromised, who had ulcerative tracheobronchitis due to Aspergillus species demonstrated histologically. Three patients had received corticosteroids or were neutropenic at presentation. At bronchoscopy, three patients had some degree of diffuse tracheobronchitis, multiple ulcerative or "plaque-like" inflammatory lesions, and occasionally nodules involving the mainstem and segmental bronchi. The remaining patient had a single deep ulceration of the proximal trachea. Aspergillus was isolated from biopsy specimens from all four patients. There were varied degrees of invasion of the mucosa, submucosa, and cartilage on histological examination in three patients, one of whom had evidence of disseminated aspergillosis. Two patients subsequently developed pulmonary parenchymal disease due to Aspergillus. A review of aspergillus tracheobronchitis, including a discussion of airway disease in patients infected with human immunodeficiency virus, is presented. PMID- 8218676 TI - Thrombotic thrombocytopenic purpura associated with human immunodeficiency virus infection: demonstration of p24 antigen in endothelial cells. AB - We report a case of thrombotic thrombocytopenic purpura (TTP) in a woman infected with human immunodeficiency virus (HIV) in whose endothelial cells we detected HIV p24 antigen. The patient had an excellent response to conventional therapy for TTP and remained in complete remission 12 months after diagnosis. We also present a review of the literature on the association of TTP with HIV infection and speculate on its nature. The presence of HIV p24 antigen in the endothelial cell might be indicative of a role of virus, yet to be defined, in the pathogenesis of HIV-associated TTP. PMID- 8218677 TI - Cerebrospinal fluid rhinorrhea and recurrent meningitis. AB - Cerebrospinal fluid rhinorrhea is the result of transdural communication between the subarachnoid space and the skull base. A transdural fistula may originate from the anterior, middle, or posterior cranial compartments. All skull-base sites of leakage potentially lead to the nasal cavity. Recurrent meningitis is commonly associated with such a direct source of bacterial contamination. Organisms associated with recurrent meningitis secondary to cerebrospinal fluid leaks are commonly found in the upper respiratory tract. We report a case of recurrent meningitis in a 5-year-old girl that highlights the problem of cerebrospinal fluid rhinorrhea, and we discuss etiology, current diagnostic techniques, and surgical management. PMID- 8218678 TI - Cefepime: the next generation? AB - Cefepime is a new aminothiazolylacetamido cephalosporin with a wider spectrum and greater potency than many currently available cephalosporins. It appears that these characteristics result from multiple properties of the molecule. In contrast to older cephalosporins, cefepime more rapidly penetrates the gram negative cell, targets multiple essential penicillin-binding proteins, and escapes the effects of many beta-lactamases due to the enzymes' low affinity for the drug. The latter characteristic is most apparent in studies of Bush group 1 beta-lactamases. Derepression of this class of beta-lactamases has less effect on the in vitro activity of cefepime than on that of other cephalosporins. The results of clinical trials should now be carefully analyzed to determine whether these advantages carry over into the clinical arena. PMID- 8218679 TI - Invasive Haemophilus influenzae infections in older children and adults in Seattle. AB - We recently saw two unusual manifestations of Haemophilus influenzae infection in adults in the Seattle area: fulminant sepsis in an otherwise-healthy man and three episodes of bacteremia in a woman with chronic liver disease. We retrospectively identified 79 bacteremic and 40 non-bacteremic cases of invasive H. influenzae infection developing in patients > or = 9 years of age between 1 January 1980 and 31 December 1990. The most common clinical presentations among patients with bacteremia included pneumonia (52%), septicemia (27%), meningitis (8%), gynecologic infection (5%), and epiglottitis (5%). Underlying illnesses were common in these patients, and overall mortality was 35.5%. Factors associated with mortality included underlying neurological disease, polymicrobial bacteremia, and advanced age. The clinical presentations of the 40 patients without bacteremia included soft-tissue abscesses (45%), lung abscesses (18%), peritonitis (13%), meningitis (8%), gynecologic infection (8%), epididymitis (5%), mastoiditis (3%), and osteomyelitis (3%). Thus H. influenzae disease has a variety of presentations and is associated with significant mortality in older children and adults. Further study is required to determine whether widespread administration of H. influenzae type b conjugate vaccine to infants will alter the development of subsequent disease in later life. PMID- 8218680 TI - Progress in the diagnosis and management of aspergillosis in bone marrow transplantation: 13 years' experience. AB - Over 13 years, we have seen 16 cases of proven invasive aspergillosis in 446 bone marrow transplant recipients, an incidence of 3.6%. The incidence of infection is low in patients with uncomplicated allogeneic or autologous bone-marrow transplants (< 2% and 0, respectively). Of the 16 episodes following transplantation, 10 occurred in patients with late transplant complications who were no longer in protective isolation. In patients who had focal pulmonary lesions (as diagnosed by computed tomographic scanning), culture of bronchoalveolar lavage (BAL) fluid was not an effective diagnostic procedure. In diffuse pulmonary disease due to Aspergillus, culture of BAL fluid had a sensitivity of 100%. Aspergillus species were isolated from an additional six patients who had no evidence of invasive aspergillosis. Graft rejection was a significant predisposing factor for the development of invasive aspergillosis (P < .001, log-rank test), and in our hospital, these patients now receive intravenous amphotericin B as prophylaxis. None of the six patients whose chest roentgenograms showed abnormalities before transplantation and who underwent surgical resection as part of the treatment for invasive aspergillosis developed recurrent infection. PMID- 8218681 TI - Antibiotic treatment of Yersinia enterocolitica septicemia: a retrospective review of 43 cases. AB - Of 53 documented cases of Yersinia enterocolitica septicemia reported to the French national registry between 1985 and 1991, 43 files contained sufficient information on antibiotic treatment to be analyzed retrospectively. All patients had at least two positive cultures of blood collected before the initiation of treatment. All strains were susceptible in vitro to the antibiotics that are usually active against gram-negative rods except for older beta-lactam agents (i.e., aminopenicillins and first-generation cephalosporins). No multiresistant strain was isolated. Only four (7.5%) of the 53 patients died. Aminopenicillins, first-generation cephalosporins, and--when prescribed alone- amoxicillin/clavulanate were not effective. Third-generation cephalosporins, most often used in combination with other antibiotics, were successful in 85% of cases. Fluoroquinolones--alone or in combination--cured all of 15 infections, with patients improving rapidly and becoming apyretic within 1-4 days. These agents therefore seem to constitute the best treatment. PMID- 8218682 TI - Efficacy of different doses of immune serum globulin in the prevention of hepatitis A: a three-year prospective study. AB - Previous studies have shown that the administration of immune serum globulin (ISG) before exposure to hepatitis A virus prevents infection. The precise dose needed and the duration of the protection conferred are unclear, however. In this study, ISG doses of 2 mL and 5 mL were used for preexposure prophylaxis, and their efficacies in reducing the attack rate of hepatitis A among Israel Defence Forces troops serving in field units were compared. The attack rate during the first 4 months of follow-up was low and was similar regardless of the dose administered (0.11/10,000 and 0.15/10,000 for 2 mL and 5 mL, respectively; P = 1.0). In the second and third 4-month intervals after immunization, attack rates were higher (but not significantly so) among soldiers given 2 mL than among those given 5 mL. Twelve months after immunization, the cumulative attack rate for hepatitis A was significantly different for the two groups (2.78/10,000 vs. 1.30/10,000; P < .05). Our data suggest that preexposure immunization with 2 mL of ISG is as effective as that with 5 mL in preventing hepatitis A for 4 months. The advantage of the 5-mL dose is evident 5-12 months after administration. PMID- 8218683 TI - Disseminated microsporidiosis due to Encephalitozoon hellem: pulmonary colonization, microhematuria, and mild conjunctivitis in a patient with AIDS. AB - Four genera of microsporidia have been associated with disease in humans, which predominantly affects immunocompromised persons. Systemic infection with a newly characterized microsporidian species, Encephalitozoon hellem, was recently reported in a patient with AIDS. This article describes a second patient with AIDS and disseminated E. hellem infection. In this case the parasite was detected in sputum, urine, and conjunctival swab specimens. Apart from recurrent mild conjunctivitis and asymptomatic microhematuria, the patient had no findings or symptoms that could be related to this parasite. Specifically, no microsporidian associated pulmonary pathology was documented. Detection of E. hellem in the patient's sputum may have epidemiological implications in that this finding suggests transmission of microsporidia by the aerosol route. Because the patient died of unrelated complications, it remains unknown whether he was an asymptomatic carrier of microsporidia or whether microhematuria heralded early microsporidian disease, with the onset of cellular damage in the urinary tract. PMID- 8218684 TI - An epidemic of infections due to Chlamydia pneumoniae in military conscripts. AB - A prospective observational study of an epidemic of infection due to Chlamydia pneumoniae strain TWAR in Finnish military trainees provided new information on immunity following infection, the range of clinical syndromes and complications, and cell culture isolation. One-half of the trainees studied (43 of 86) had laboratory evidence of C. pneumoniae infection. The etiologic association of C. pneumoniae with disease was strengthened by the sharp increase in cases of pneumonia and in outpatient visits for acute respiratory disease along with the laboratory evidence of infection. The pattern of serological response suggested that 23 of the trainees had a primary TWAR infection and 20 had a reinfection. Evidence that prior infection modified the illness included the frequency of hospitalization (12 with primary infections vs. 1 with reinfection), the development of pneumonia (10 vs. 0), and the requirement for repeated courses of antibiotic therapy (13 courses vs. 0). Isolation was more frequent in HL cells (n = 25) than in HeLa 229 cells (n = 10). PMID- 8218685 TI - Fascioliasis: case reports and review. AB - Fasciola hepatica, a zoonotic liver fluke, can cause disease in humans. Fascioliasis, while common in some tropical and developing countries, is uncommon in the United States. We report two cases of fascioliasis that illustrate both the hepatic and biliary stages of the disease. Clinical features and diagnostic aspects including serologic, radiographic, and histopathologic studies are emphasized. Praziquantel was ineffective in treatment of both patients. Bithionol appears to be an effective treatment for fascioliasis. PMID- 8218686 TI - Gastrointestinal visceral motor complications of dermatomal herpes zoster: report of two cases and review. AB - Motor complications are uncommon manifestations of herpes zoster. This report describes two cases of gastrointestinal visceral motor manifestations associated with dermatomal herpes zoster and reviews the English-language literature since 1900. The 17 cases reviewed were divided clinically into two groups: colonic pseudo-obstruction and localized colonic spasm. Characteristics of the patients, radiographic study results, endoscopic findings, proposed pathogenesis, and management options are discussed. It is important to recognize this manifestation in order to institute proper management and avoid unnecessary surgery, given the complete resolution with conservative management in most cases. PMID- 8218687 TI - Recurring ventriculitis due to Citrobacter diversus: clinical and bacteriologic analysis. AB - Neonatal meningitis due to Citrobacter diversus is usually accompanied by the development of brain abscesses and tends to have high rates of morbidity and mortality. We report a case of a newborn with C. diversus meningitis and brain abscesses who relapsed after initial antibiotic therapy and from whom C. diversus was recovered from cerebrospinal fluid 4 years later during a neurosurgical procedure. Genetic differences in the early and late isolates were discovered, and explanations for this phenomenon are suggested. Possible mechanisms for prolonged persistence in the central nervous system are explored. This unusual case and the analysis of the organisms illustrate the unique features of C. diversus as a pathogen and underscore the need for developing optimal therapeutic strategies. PMID- 8218688 TI - An economic evaluation of varicella vaccine for pediatric liver and kidney transplant recipients. AB - To evaluate the potential benefit of varicella vaccine for pediatric liver and kidney transplant patients, we determined the consequences of varicella susceptibility for a cohort of susceptible children (n = 44) who received transplants between July 1986 and June 1990 at the Hospital for Sick Children, Toronto. Costs of these consequences were compared with costs with a hypothetical varicella vaccination program in place. The median follow-up was 11.4 months (range, 2-50 months). Total costs in Canadian dollars to the health service without a program were for varicella-related hospital stay ($135,675) and varicella-zoster immune globulin ($4,322). Costs to parents were for lost time ($13,590) and transport ($414). Assuming a vaccine cost of $30/dose and a 90% vaccine efficacy, a pretransplantation vaccination program would have cost $16,205 and saved $3,132/child ($304 for families and $2,828 for the health service) during the study period. Varicella vaccination prior to solid organ transplantation should reduce morbidity in pediatric recipients and provide considerable savings for families and the health system. PMID- 8218690 TI - Prevalence of self-medication with antibiotics among patients attending a clinic for treatment of sexually transmitted diseases. AB - To ascertain the prevalence of self-medication with antimicrobial agents among patients attending a clinic for treatment of sexually transmitted diseases (STDs), we administered a questionnaire to and collected a urine specimen for antimicrobial testing from 551 patients before treatment. We defined self medication as an antimicrobial agent taken on the patient's own initiative by self-report during the week before the visit to the clinic or a positive urine assay for antimicrobial agents at the time of the clinic visit. We tested urine for the presence of antimicrobial agents by a disk diffusion method using Sarcina lutea as the test organism. A total of 75 (14%) of the 551 participants were self medicators: 19 reported antimicrobial use and had a positive urine test, 27 reported antimicrobial use but had a negative urine test, and 29 denied antimicrobial use but had a positive urine test. Thus, 29 (60%) of the 48 patients with antimicrobial agents detected in their urine at the time of the clinic visit denied self-medication. Self-medicators acquired their antibiotics either from their medicine cabinet (44%) or from a family member or friend (56%). Self-medication was associated with self-report of prior use of unprescribed antimicrobial agents (P < .0001). We concluded that use of unprescribed antimicrobial agents (usually beta-lactam agents or tetracyclines) among STD clinic attendees in our study was common and that self-reporting was not a reliable method of screening for self-medicators. PMID- 8218689 TI - Chorioamnionitis caused by Capnocytophaga: case report and review. AB - We report a case of pathologically demonstrated chorioamnionitis due to Capnocytophaga species. The mother had high fever and marked uterine tenderness, and the infant had poor Apgar scores, fever, and pulmonary infiltrates. Both recovered after receiving specific antibiotics. Pathological examination of the placenta revealed acute chorioamnionitis, subchorionitis, and vasculitis of the umbilical vein. The dramatic clinical and pathological features of this case are compared with those of the nine previously reported cases of infection due to Capnocytophaga species occurring in pregnancy. PMID- 8218691 TI - Elimination of Staphylococcus aureus nasal carriage in health care workers: analysis of six clinical trials with calcium mupirocin ointment. The Mupirocin Collaborative Study Group. AB - Six double-blind, independently randomized studies evaluated the efficacy and safety of calcium mupirocin ointment in eliminating nasal carriage of Staphylococcus aureus among health care workers. Healthy volunteers with stable nasal carriage of S. aureus (n = 339) received either calcium mupirocin ointment (n = 170) or an identical placebo ointment (n = 169) intranasally for 5 days. Nasal carriage was eliminated 48-96 hours after completion of treatment in 130 (91%) of 143 evaluable volunteers receiving mupirocin but in only 8 (6%) of 142 evaluable volunteers receiving placebo. The 85% crude difference represents a 90% pooled (adjusted) estimate of the risk difference (95% confidence interval, 0.86 0.95) and a risk ratio of 16 (P < .0001). This effect of treatment with mupirocin was observed consistently (risk ratio, 8-32) in all six centers. In addition, 96 of the 130 mupirocin-treated volunteers and 1 of the 8 placebo-treated volunteers who were culture-negative at the end of therapy remained free of S. aureus 4 weeks after treatment. Adverse events in each treatment arm were mild and equally frequent. These data, consistent across six institutions, demonstrate that calcium mupirocin ointment administered intranasally for 5 days is safe and effective in eliminating stable nasal carriage of S. aureus. PMID- 8218692 TI - A 9-year follow-up study of the immunogenicity and long-term efficacy of plasma derived hepatitis B vaccine in high-risk Chinese neonates. AB - The long-term immunogenicity of and protection provided by a plasma-derived hepatitis B vaccine was determined in a cohort of 98 susceptible Chinese neonates immunized in 1982-1983. Within 24 hours of birth, 89 infants received the first of three 30-micrograms doses of vaccine (at 0, 1, and 6 months) and were subsequently followed up by testing for serological markers of hepatitis B virus and by determining levels of alanine aminotransferase annually for 9 years. After the primary series of vaccine doses, 74 (83%) of 89 subjects developed antibody to hepatitis B surface antigen (anti-HBs). At the 9-year follow-up, 51% of vaccinees still had levels of antibody of > or = 10 mIU/mL, considered the protective level. Seven responders to vaccine (9.4% of 74 evaluable patients) developed antibody to hepatitis B core antigen, and in six of these responders, levels of anti-HBs increased transiently. None of the vaccinees developed chronic carriage of hepatitis B surface antigen or clinical hepatitis. Immunization of high-risk neonates with a plasma-derived hepatitis B vaccine can induce long lasting protective immunity that can prevent or modify primary infection for at least 9 years. Booster doses are not necessary during this period. PMID- 8218693 TI - Intestinal coinfection with Enterocytozoon bieneusi and Cryptosporidium in a human immunodeficiency virus-infected child with chronic diarrhea. AB - The microsporidian Enterocytozoon bieneusi has been recognized as an important cause of chronic diarrhea in severely immunodeficient adults infected with human immunodeficiency virus (HIV). We report the first case of intestinal E. bieneusi infection in a child. The 9-year-old boy with connatal HIV infection presented with failure to thrive, chronic diarrhea, and intermittent abdominal pain. His CD4 lymphocyte count was 0.05 x 10(9)/L and dropped to 0.01 x 10(9)/L. No HIV associated opportunistic infection other than oral hairy leukoplakia and oral candidiasis had been found before microsporidia were detected. Treatment of microsporidiosis with albendazole was of no benefit. During follow-up, the boy also developed intestinal cryptosporidiosis. Evaluation of chronic diarrhea in severely immunodeficient HIV-infected children should include examination for intestinal microsporidia. We recommend the use of a new coprodiagnostic technique that allows detection of microsporidial spores in stool specimens. Furthermore, consideration of dual or even multiple parasitic infections in the differential diagnosis of chronic diarrhea may have both important clinical and epidemiological implications. PMID- 8218694 TI - Typhlitis in children with cancer: a 30-year experience. AB - We identified 24 children treated for malignancies between 1962 and 1992 who had antemortem diagnoses of typhlitis that were confirmed on review. The study criteria specified the presence of fever, abdominal pain, and tenderness, with radiological evidence of right-sided colonic inflammation. Typhlitis was most frequent in patients treated for acute leukemias. Computed tomography and ultrasonography were more sensitive than plain radiography (false-negative rates, 15%, 23%, and 48%, respectively). The wider availability of these sensitive procedures and the increased intensity of chemotherapeutic regimens may account for a marked increase in the incidence of typhlitis over the past 5 years. Most patients responded to aggressive medical management, and typhlitis was fatal in only two cases (1 of 21 cases managed medically and 1 of 3 taken to surgery). Seven patients are alive > 1 year following the diagnosis. These findings contrast with prior descriptions of typhlitis as a preterminal event. Computed tomography and/or ultrasonography should be performed in all neutropenic patients with right-lower-quadrant signs to permit prompt diagnosis and treatment. PMID- 8218695 TI - Clinical pharmacokinetics of continuous intravenous administration of penicillins. AB - Theoretically, continuous intravenous administration of beta-lactam antibiotics has advantages over intermittent administration because of the close relationship between efficacy and the time the plasma concentration remains above the minimal inhibitory concentration that has been found in vitro. The aim of the present study was to establish the pharmacokinetic parameters of benzylpenicillin and cloxacillin administration in patients receiving high-dose benzylpenicillin or cloxacillin therapy by continuous infusion. A major part of the interindividual variation in the plasma concentrations at steady-state was attributable to variation in renal function, as estimated by the creatinine clearance. On the basis of these results, a nomogram was constructed that can be used to determine on an individualized basis the total daily dose of benzylpenicillin or cloxacillin necessary for each patient to obtain therapeutic plasma concentrations. PMID- 8218696 TI - Spread of methicillin-resistant Staphylococcus aureus in a hospital after exposure to a health care worker with chronic sinusitis. AB - A dramatic increase in the incidence of methicillin-resistant Staphylococcus aureus at a teaching hospital was documented to be due to three factors: a hospital-wide outbreak of 32 cases caused by an epidemic strain, an increase in the number of nosocomial cases caused by several other strains, and an increase in the number of patients admitted carrying strains acquired at other institutions. Case patients with the epidemic strain were significantly more likely than control patients to have had previous exposure to a respiratory therapist (P = .005) who had chronic sinusitis due to the epidemic strain. The plasmid DNA of isolates from the implicated respiratory therapist and affected patients yielded the same patterns on restriction endonuclease digestion. Implementation of general control measures and eradication of the respiratory therapist's sinusitis and nasal carriage terminated the epidemic. Establishing the importance of the infected health care worker by epidemiological methods led to control of the outbreak without the institution of wide-scale culture of specimens from personnel and the environment or other expensive and labor intensive measures. PMID- 8218697 TI - Nonfatal and fatal infections caused by Chromobacterium violaceum. AB - Human infection caused by Chromobacterium violaceum is rare, but when it occurs it is associated with a high mortality rate. We report the cases of two patients with infection due to Chromobacterium violaceum. One patient presented early in the course of disease and survived after receiving appropriate antibiotic therapy. The other patient presented late in the course of disease and died of fulminant sepsis with abscesses in multiple organs. We discuss the similarity between C. violaceum infection and the septicemic form of melioidosis. PMID- 8218698 TI - Mycobacterium simiae infection in Israeli patients with AIDS. AB - Mycobacterium simiae is an environmental organism that has rarely been associated with human disease. In Israel M. simiae is frequently isolated from clinical specimens, and it usually colonizes damaged lungs. Until now, only two cases of AIDS patients with M. simiae infection have been reported, and these patients were coinfected with Mycobacterium avium complex. Two Israeli patients with AIDS complicating hemophilia developed prolonged fever that was unresponsive to therapy with broad-spectrum antibiotics. One of them had cavitary pulmonary infiltrates. M. simiae was isolated from blood in both cases and from sputum and bone marrow in one case. The identity of the mycobacterium was confirmed at three reference laboratories. Both patients died of the infection. Thus, the possibility of M. simiae infection should be considered for AIDS patients who live in areas where this mycobacterium is prevalent. PMID- 8218699 TI - Malaria in Mogadishu, Somalia. PMID- 8218700 TI - Clinical value of blood cultures for detection of Toxoplasma gondii in human immunodeficiency virus-seropositive patients with and without cerebral lesions on computerized tomography. PMID- 8218701 TI - CDC group IV c-2 as a cause of catheter-related sepsis in an immunocompromised patient. PMID- 8218702 TI - Combination antibiotic treatment with clarithromycin for human immunodeficiency virus-associated Rhodococcus equi infection. PMID- 8218703 TI - Liver abscess due to Corynebacterium jeikeium in a patient with AIDS. PMID- 8218704 TI - Pubic osteomyelitis due to Pseudomonas aeruginosa. PMID- 8218705 TI - Necrotizing fasciitis, bacteremia, and multiorgan failure caused by Ochrobactrum anthropi. PMID- 8218706 TI - Unsuccessful treatment of Legionella pneumophila infection with a fluoroquinolone. PMID- 8218707 TI - CSF shunt infection by unencapsulated Haemophilus influenzae. PMID- 8218708 TI - Septic arthritis due to a nontoxigenic strain of Corynebacterium diphtheriae subspecies mitis. PMID- 8218709 TI - Neopterin levels during acute rubella in children. PMID- 8218710 TI - Cytomegalovirus ventriculoencephalitis with cranial radiculitis in patients with AIDS: a distinct clinical entity. PMID- 8218711 TI - Acute Lyme disease in an American tourist returning from Germany. PMID- 8218712 TI - Catheter-related endocarditis due to glycopeptide-resistant Enterococcus faecalis in a transplanted heart. PMID- 8218713 TI - Iatrogenic meningitis due to Streptococcus salivarius following a spinal tap. PMID- 8218714 TI - Reiter's syndrome after administration of intravesical bacille Calmette-Guerin. PMID- 8218715 TI - Streptococcus bovis meningitis: no association with colonic malignancy. PMID- 8218716 TI - Famous names in toxicology. PMID- 8218717 TI - Adverse reactions and interactions with herbal medicines. Part 2--Drug interactions. PMID- 8218718 TI - Drugs causing gastrointestinal obstruction. PMID- 8218719 TI - Toxicity of aluminium: a historical review, Part 2. PMID- 8218720 TI - Histological reaction to titanium alloy and hydroxyapatite particles in the rabbit tibia. AB - The interfacial membrane harvested from failed joint replacements contains particulate debris from the materials used for the implant. To define the tissue response to particulate titanium alloy and hydroxyapatite (HA) alone, 16 mature New Zealand white rabbits were divided into 2 groups of 8 rabbits. Using sterile technique, a drill hole was placed anteromedially in the tibia, 1 cm distal to the knee joint bilaterally. The marrow was scooped out and 0.25 mg of either titanium alloy particles or HA particles were inserted in the right tibia. The titanium alloy particles had a diameter averaging 4.0 +/- 4.4 microns (mean +/- standard deviation) and an aspect ratio (the ratio of the maximum length divided by the maximum width) of 1.84. The HA particles had a diameter of 4.4 +/- 3.3 microns and an aspect ratio of 1.76. The left leg was prepared in a similar fashion, but no biomaterial was implanted. The animals were killed after 16 wk. The harvested tibiae were processed with decalcification and the plastic-embedded sections were subjected to histomorphological analysis. Black titanium alloy particles were present within the bone marrow fat between haematopoietic cells, and within scattered macrophages. The surrounding bone appeared to be unaffected. Within the spongiosa, the HA particles were surrounded by small numbers of mononuclear histiocytes or encased within a shell of new appositional bone. Where HA deposits were exposed to the endosteal aspect of bone, there was scalloping of the surface of the HA in a pattern suggestive of resorption or dissolution of the HA particles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218721 TI - Study on the efficacy of biodegradable poly(L-lactide) mesh for supporting transplanted particulate cancellous bone and marrow: experiment involving subcutaneous implantation in dogs. AB - Poly(L-lactide) (PLLA) mesh sheets, monofilaments and mesh cylinders filled with fresh autogenic particulate cancellous bone and marrow (PCBM) were implanted subcutaneously into the back of 22 adult dogs for 1 yr. Polypropylene (PP) was used as a control. The inflammatory response to PLLA mesh sheets was slight, similar to PP mesh sheets. However, 3 months after implantation, histiocytes and multinucleate giant cells appeared on the surface of the monofilaments of PLLA mesh sheets and gradually increased in number as the monofilaments were degraded and absorbed. Almost no inflammatory cellular infiltration was seen in the tissue around PLLA mesh sheets or between the monofilaments. When a PLLA mesh cylinder filled with PCBM was implanted subcutaneously, the bone formation reached its peak 1 month after implantation, as in the case of a similar PP mesh cylinder, and bone formation was observed along the inner wall of the cylinder. In addition, a vascular net was abundant within the cylinder. The mechanical strength of the test material (PLLA monofilaments) did not change for almost 2 months after implantation, and 80% of its initial strength was retained for 3 months. These observations suggest that a PCBM graft supported by PLLA mesh would be very effective in the reconstruction of damaged maxillofacial bones, since histological tissue reactions associated with biodegradation of the PLLA mesh are mild and the PLLA mesh does not interfere with bone formation of PCBM. It was also found that the PLLA mesh retains its mechanical strength long enough to allow the PCBM transplant to develop sufficient strength to sustain the damaged region. PMID- 8218722 TI - Cyanoacrylate tissue adhesive for closing skin wounds: a double blind randomized comparison with sutures. AB - A comparative double blind randomized study was undertaken in the rat, to compare the external cosmetic and the morphologic aspect of skin wounds, treated by the local application of adhesive glue (ethyl-2-cyanoacrylate-Mediglue) or classical suture technique. Skin incisions were applied and treated by a plastic surgeon, then photographed or biopsied, and evaluated and scored by independent observers, not aware of the initial treatment. Small (1.5 cm) or long (8 cm) incisions were made, on both sides of the back, and treated randomly on one side by glue and on the other side by sutures. Evaluations were performed at 1, 2, 4 and 8 wk. Both small and large wounds scored identically, irrespective of the treatment (overall score 1.5 cm wounds: 8.8 +/- 1.4 for glue versus 8.8 +/- 1.0 for sutures; 8 cm wounds: 8.3 +/- 1.9 versus 8.3 +/- 1.5; P = not significant). A morphological study demonstrated no adverse effects for the adhesive treatment, with a minor inflammatory infiltrate. Sutured wounds had a higher tendency to develop abscesses and/or major inflammation. Adhesive-treated wounds scored better than non-treated wounds (8.9 +/- 1.3 versus 7.4 +/- 3.3, P < 0.01). In conclusion, this controlled comparative study shows no difference in cosmetic aspect between adhesive and suture-treated skin incisions. Morphologically, the glue treatment is not related to any adverse effect or damage to the skin structures. PMID- 8218723 TI - Production of artificial-orientated mats and strands from plasma fibronectin: a morphological study. AB - Fibronectin is an extracellular matrix glycoprotein involved in wound healing. Techniques have been developed for the preparation of orientated fibronectin mats from plasma fibronectin, for use in wound healing and tissue repair. Formation of strands and mats is by self-association and aggregation of fibronectin from solution under a directional shear force. Incorporation of heparin with fibronectin modified the mats. Scanning electron microscopy showed that the mats were composed of well-orientated fibrous fibronectin, with a network of internal interconnecting pores. Single strands of fibronectin were prepared for use as a tissue culture model of cell interaction with aggregated orientated fibronectin mats. Rat tail tendon and human skin fibroblasts were used for assessment of cell interaction with both single strands of fibronectin and mats. Fibroblasts rapidly attached to single strands and became orientated. Dense cultures of fibroblasts growing over single strands became orientated, according to the orientation of the underlying fibronectin. Fibroblasts readily grew on the surface of fibronectin mats and were observed within the porous network. PMID- 8218724 TI - Collagen synthesis by fibroblasts cultured within a collagen sponge. AB - We prepared a collagen sponge made of type I and III bovine collagen, glycosaminoglycans (GAG) and chitosan. Fibroblasts grown within the collagen sponge express a sixfold increase of their collagen synthesis, compared with fibroblasts embedded in a collagen gel. Moreover, collagen synthesis is twice as high in the collagen sponge than in a monolayer culture. The collagen sponge culture system promotes a dynamic model for us to perform studies on the regulations of collagen synthesis. Increased collagen production within the collagen sponge leads fibroblasts to reconstitute their own extracellular matrix, which should be more physiological than a bovine collagen gel. PMID- 8218725 TI - Towards the preparation of a MMA-PEO block copolymer for the microencapsulation of mammalian cells. AB - Polymethyl methacrylate-polyethylene glycol-polymethyl methacrylate triblock copolymers (PMMA-PEO-PMMA) were synthesized by reductive amination coupling of preformed aldehyde-terminated PEO and amine-terminated PMMA. These were intended for use as high water content and therefore high permeability, biocompatible encapsulating materials for mammalian cells. Evidence for the formation of the block copolymer was obtained indirectly from precipitation experiments and IR analysis of the water-soluble extract of the polymer. Unfortunately the pure copolymer could not be separated from the homopolymers, because of the difficulty in finding appropriate non-solvents and the apparently limited yield of the product. Further work is necessary to confirm the underlying hypothesis of this work, i.e. that such a block copolymer would have a high permeability to the small proteins critical to microencapsulated cell survival or function. PMID- 8218726 TI - Trypsin immobilization on to polymer surface through grafted layer and its reaction with inhibitors. AB - Trypsin was covalently immobilized and physically adsorbed on to the surface of poly(ethylene terephthalate) fibres using poly(acrylic acid) (PAAc) chains grafted on to the ozonized fibres. The covalent immobilization was accomplished through amide formation between amino groups of trypsin and carboxyl groups of grafted PAAc chains, with the use of water-soluble carbodiimide. A set of samples with surface concentrations of grafted polymer ranging from 0.03 to 2.5 micrograms/cm2 was used to study the effects of grafted layer on the enzymatic activity of immobilized trypsin and its inhibition by trypsin inhibitors of different molecular sizes. The amount of immobilized trypsin increased linearly with an increase in graft yield of fibres, but the activity of immobilized enzyme reached saturation at a certain graft yield, probably because of diffusion limitation for the transport of enzyme substrate molecules into the grafted PAAc layer. The reduction of inhibition with an increase in graft yield and in molecular weight of inhibitors was attributed to enhancement of steric hindrance and enzyme inactivation in the dense grafted layer. We also found that the adsorbed trypsin was inhibited more easily than the covalently immobilized at any concentration of the grafted PAAc and for any type of inhibitor used. PMID- 8218727 TI - Distribution of zinc ions from orthophosphate cements at the cement-tooth interface in fixed dental prosthesis. AB - Cast metal prostheses are considered to be one of the best ways to restore the morphology and function of missing teeth. However, the success of fixed prosthesis therapy is mainly to be judged on its durability. It is therefore important to know how cemented prostheses behave in the mouth. A protocol for an in vivo study was set up to analyse the influence of time on the release of zinc ions from zinc orthophosphate cements used at the tooth-prosthesis interface. PMID- 8218728 TI - Processing shrinkage of heat-curing acrylic resin reinforced with high performance polyethylene fibre. AB - The incorporation of high-performance polyethylene fibre into acrylic denture base resin produced a very significant decrease in the processing shrinkage of the material, explained by the highly anisotropic mechanical and thermal properties of the fibres. PMID- 8218729 TI - Variation of Young's modulus with the test specimen's aspect ratio. AB - A study of Young's modulus in flexure of a number of methacrylate polymers indicated that the results were dependent on the test specimen thickness. The Young's modulus calculated from simple bending theory decreased with increased specimen thickness. This effect could not be accounted for either by the usual corrections for shear or corrections for the effect of the width/length ratio. It transpires that the effects noted experimentally are due to the combined effects of shear and the width/length ratio. PMID- 8218730 TI - Immobilization of proteins on poly(methyl methacrylate) films. AB - Polymethyl methacrylate (PMMA) films were treated by oxygen plasma discharge followed by acrylic acid (AA) grafting. The amount of carboxyl groups introduced by the grafting of AA on to the film surfaces was in the range 0.47-9.48 mumol/cm2, depending on the pressure of the plasma chamber during the discharge treatment. The carboxyl groups of the PMMA film surface previously activated with water soluble carbodiimide were coupled with bovine serum albumin, collagen and gelatin. The protein immobilization on the surface was confirmed by attenuated total reflection Fourier transform infra-red spectroscopy (ATR-FTIR) and electron spectroscopy for chemical analysis (ESCA). The amount of albumin, collagen and gelatin immobilized on the PMMA surface was 6.25, 7.25 and 13.75 micrograms/cm2, respectively, as determined by the coomassie brilliant blue-protein interaction. The water contact angle of the PMMA film was markedly decreased by oxygen plasma treatment, AA grafting or protein immobilization, indicating the increase of hydrophilicity of the surface-modified PMMA films. The protein-immobilized PMMA films may be widely used as a biocompatible material. PMID- 8218731 TI - Development of a degradable composite for orthopaedic use: mechanical evaluation of an hydroxyapatite-polyhydroxybutyrate composite material. AB - This study evaluates the mechanical properties of a composite material comprising polyhydroxybutyrate with hydroxyapatite added in proportions varying from 0 to 50%. Among the three methods of production, injection moulding was found to result in the most satisfactory mechanical properties. The tensile and compressive strength and the modulus of elasticity of composite produced in this way fell within the range for fresh human bone from different anatomical sites. With the additional advantages of biocompatibility, biodegradability and the potential for piezoelectric stimulation of new local bone formation, it was concluded that the injection-moulded composite material has considerable potential for use in orthopaedic surgery, both as a material to construct certain orthopaedic implants and as an alternative to corticocancellous bone graft. PMID- 8218732 TI - Biodegradable poly(DL-lactic acid) formulations in a calcitonin delivery system. AB - A synthetic analogue of eel calcitonin, [Asu1, 7]-ECT, was incorporated into biodegradable poly(DL-lactic acids) with number-average molecular weights (Mn) of 1400-4400 by the melt-pressing technique. The in vitro release of drug from a parabolically degradable poly(DL-lactic acid) with Mn = 1400 showed an initial burst release and completed the release in 3 d from the start of the test. The drug release from a Mn = 4400 polymer with an S-type degradation pattern was kept at 14 +/- 5 units/d for an experimental period of 24 d. PMID- 8218733 TI - Bioreactor applications of glucose oxidase covalently bonded on pHEMA membranes. AB - Glucose oxidase was immobilized onto poly(2-hydroxyethyl methacrylate) membranes by covalent bonding through epichlorohydrin. The highest immobilization efficiency was found to be 17.4%. The Km values were 5.9 and 8.8 mM for free and bound enzymes, respectively, and the Vmax values were 0.071 and 0.067 mM/min for free and bound enzymes. When the medium was saturated with oxygen Km was not altered significantly but Vmax was. The optimum pHs for the free and bound enzyme were determined to be 5 and 6, respectively, and the optimum temperature was 30 degrees C for both forms. The inactivation constant for the bound enzyme was found to be 1.7 x 10(-4) min-1. PMID- 8218734 TI - Glucose oxidase sandwiched between pHEMA layers: a continuous flow reactor application. AB - Glucose oxidase was entrapped between poly(2-hydroxyethyl methacrylate) membranes and conditions were optimized for high enzyme activity and high levels of entrapment. Highest entrapment was with a 78 microns thick coat. A continuous flow membrane reactor was designed and used. The reaction was first order with respect to glucose and to oxygen. Vmax values for the native and immobilized enzymes were 0.182 and 0.133 mM/min. The Km's for native and immobilized enzymes were 6.2 and 16.9 mM, respectively. At high substrate concentrations enzyme poisoning was detected. Both pH and temperature profiles moved to higher values upon immobilization. The enzyme retained 80% of its activity for at least 3 months in dry form. PMID- 8218735 TI - Introduction of functional groups onto the surface of polyethylene for protein immobilization. AB - Amino and carboxyl groups could be introduced onto the surface of high-density polyethylene film by utilizing graft polymerization of acrylamide and the subsequent Hofmann degradation and alkaline hydrolysis of grafted polyacrylamide. Graft polymerization was carried out by immersing an argon-plasma treated film in an aqueous solution of the monomer, followed by heating after degassing the monomer/film mixture. The surface density of these functional groups could be increased up to 10(-7) mol/cm2. The surfaces having amino and carboxyl groups exhibited positive and negative zeta potentials, respectively, when contacted with KCl aqueous solution. Both of the functional groups introduced onto the polyethylene surface were found to be utilizable for covalent immobilization of protein using carbodiimide for the carboxylic group or mediators such as glutaraldehyde and ethylene glycol diglycidyl ether for the amino group. PMID- 8218736 TI - Surface modification of nanoparticles by PEO/PPO block copolymers to minimize interactions with blood components and prolong blood circulation in rats. AB - The biological fate of injected foreign particles is believed to be closely related to their interactions with blood plasma proteins and cells. In order to verify this correlation, we have quantitatively measured protein adsorption and blood retention profiles in rats by using model polystyrene latex nanoparticles. The in vitro interactions of these non-biodegradable particles with plasma proteins and whole blood can be altered by modifying their surfaces with a family of amphiphilic polymeric surfactants, PEO/PPO Pluronic or Tetronic block copolymers. Protein adsorption was measured by several techniques, including photon correlation spectroscopy, centrifugation, high performance liquid chromatography and field-flow fractionation. Pluronic F108 and Tetronic 908 and 1508 copolymers (with PEO terminal block MWPEO > 5000, PPO middle block MWPPO > 3000, and HLB values > 24) were shown to be the most effective surface modifiers in reducing adsorption of plasma proteins on the particles. Minimum interaction of coated particles with whole blood was also observed by optical microscopy. The blood circulation half-life of the particles injected in rats was increased from 20 min to 13 h when the latex particles (75 nm) were precoated with these block copolymers. These results suggest that nanoparticles designed for use as injectable drugs or drug carriers should display similar surface characteristics provided by such amphiphilic surface modifiers. PMID- 8218737 TI - Effect of protein adsorption on the blood-contacting response of sulphonated polyurethanes. AB - Polyurethanes which are grafted with propyl sulphonate functionality have excellent blood-contacting properties. In a canine ex vivo series shunt experiment, very low platelet deposition was observed on these materials and those platelets which were adherent remained unspread. In contrast to this, large amounts of fibrinogen, of the order of a monolayer or greater, were deposited on these surfaces in this ex vivo experiment. This led to the hypothesis that perhaps the deposited fibrinogen did not retain its platelet-adhesive activity. In this paper, we investigate the possibility that these materials exert their antithrombotic effects through the adsorbed protein layer. Protein adsorption kinetics and isotherms on these sulphonated polyurethanes are determined. Multilayer protein adsorption or absorption into the hydrogel-like materials is found for each of the proteins studied, and the greatest amounts of protein are seen on the most highly sulphonated polyurethanes. Further, the blood-contacting response of these materials is investigated after pre-conditioning with either fibrinogen, fibronectin or albumin. When these materials are pre-adsorbed with either fibrinogen or fibronectin, a very thrombogenic response was observed, which suggests that the platelet-adhesive activity of these proteins is not being reduced. Pre-adsorption of albumin did not improve the thromboresistance of these surfaces. PMID- 8218738 TI - Field-dependent fibroblast orientation on charged surfaces is independent of polarity and adsorbed serum proteins. AB - Electrets were used to induce a dipolar charge on fluorinated ethylene propylene (FEP) and bacteriological grade polystyrene (PS) films. The serum protein surface concentration adsorbed on FEP and PS from cell-free media was dependent on both the magnitude and the polarity of the surface charge density. Chick embryo fibroblasts were cultured on charged and uncharged FEP surfaces, and cellular orientation and biosynthetic activity (protein synthesis) were determined. The orientation of fibroblasts was found to be significantly dependent on the magnitude of the surface charge but independent of its polarity. The biosynthetic activity of fibroblasts was observed to be dependent on both magnitude and polarity of the surface charge density. PMID- 8218739 TI - Surface modification of intravenous catheters to reduce local tissue reactions. AB - Surface modification of polymer materials used in intravascular catheters reduces the in vitro adhesion of plasma proteins involved in blood coagulation. Intravenous Teflon cannulae, native and surface-modified with ethyl hydroxyethyl cellulose, were compared using clinical examination and laser Doppler flowmeter (LDF) measurements of local cutaneous blood flow. Nine volunteers were simultaneously subjected to both types of cannulae for a period with a maximum of 4 d. Native Teflon catheters showed a larger incidence of catheter-associated tissue reactions, first demonstrated by early increases in laser Doppler recordings of skin blood flow. These results indicate that surface modification of polymer intravascular catheters attenuates tissue response against the foreign material and that altered LDF measurement precedes the clinical recognition of thrombophlebitis. PMID- 8218740 TI - Effect of hirudin on platelet deposition to an artificial surface during low stress shear flow of whole blood. AB - The effect of hirudin, a known inhibitor of thrombin, was evaluated for whole blood samples in terms of platelet deposition/adhesion to a non-biological test surface (tetrafluoroethylene-propylene copolymer), adenosine diphosphate (ADP) release and reduction in platelet count during laminar shear flow for a shear rate to 5680 s-1 (corresponding to a shear stress of about 150 dynes/cm2). Experiments were done in a cone-and-plate viscometer for samples of whole blood with and without the addition of hirudin. Whole blood samples containing hirudin showed about a 50% reduction in platelet surface coverage compared with blood samples not containing hirudin. Results on low-stress, shear-induced release of ADP showed that for shear rates of 2860 s-1 and above there was an increase in ADP release for the blood samples not containing hirudin compared with the hirudin-treated samples. However, no differences in haemoglobin leakage from red blood cells as well as residual platelet count following shear were observed between both types of blood samples. PMID- 8218741 TI - Polymerization contraction and conversion of light-curing BisGMA-based methacrylate resins. AB - The aim of this study was to investigate the polymerization contraction and the conversion of light-curing methacrylate resins based on bisphenol-A bis(2 hydroxypropyl)methacrylate (BisGMA) diluted with triethylene glycol dimethyacrylate (TEGDMA), methyl methacrylate (MMA), hydroxypropyl methacrylate (HPMA) or (+/-)-2-ethylhexyl methacrylate (EHMA). The contraction measurements were carried out with a linometer, a simple device to determine true linear polymerization contraction of liquid monomers at ambient temperature. The contraction increased with the amount of diluting monomer. The estimated conversion of the BisGMA-TEGDMA, calculated using the contraction, is consistent with literature values. The BisGMA-HPMA mixtures showed high conversions at moderate contraction. PMID- 8218742 TI - Pin-hole shear stresses generated by conical and standard external fixation pins. AB - Pin-hole shear stresses generated by tapered (conical) and untapered (standard) external fixator pins were compared using a photoelastic technique. The results show that shear stresses progressively increase as a conical pin is inserted but remain the same for the standard pin irrespective of the depth of insertion. PMID- 8218743 TI - Bone formation over a TiAl6V4 (IMZ) implant placed into an extraction socket in association with membrane therapy (Gengiflex). AB - Complete restoration of an osseous defect around a TiAl6V4 (IMZ) implant is accomplished by the combined use of an implant placed in the alveolus of a fractured lower bicuspid and the principles of guided tissue regeneration. Gengiflex (Gengiflex--BioFill--Productos Biotecnologicos, Curitiba, PR, Brazil), a new membrane, was used to cover the implant and porous hydroxyapatite was used as grafting material. The filling of the osseous defect that also covered the implant was verified clinically at re-entry 6 months later. Histological analysis of the mineralized tissue collected during exposure of the implant confirmed bone formation. PMID- 8218744 TI - Microbial colonization on natural tooth structure compared with smooth and plasma sprayed dental implant surfaces. AB - The purpose of this study was to characterize and compare by scanning electron microscopy (SEM) the maturation of supragingival microbial plaque on enamel and smooth titanium and that of subgingival plaque on cementum, plasma-sprayed titanium and hydroxyapatite surfaces. Specimens (6.5 x 2 x 1 mm) were obtained from titanium implants with smooth transmucosal collars and plasma-sprayed endosseous posts of titanium or hydroxyapatite. Unerupted third molars were sectioned to similar dimensions that included equal lengths of enamel and root surface. Ten patients with post-treatment pocket depths of > 6 mm on 3 non adjacent teeth were selected and each had 1 set of the 3 specimen types bonded by random assignment to the selected teeth. Specimens were positioned so that enamel and/or smooth titanium surfaces were supragingival and cementum and titanium or hydroxyapatite plasma-sprayed surfaces were subgingival. Patients were instructed to stop oral hygiene, after which 2 specimen sets were removed at 1, 3, 5, 7 and 10 days. Two specimens of each type were examined by SEM at each time interval for supra- and subgingival plaque. The sequence of appearance of various microbial morphotypes in supra- and subgingival plaque was similar regardless of surface. In both supra- and subgingival plaque, depending on time interval, cocci, rods of various lengths, filamentous organisms, fusiforms, spirochetes and corn-cob formations were observed. Mineralized plaque was noted on most subgingival specimens by day 10. These observations indicate that surface of natural teeth, smooth titanium and plasma-sprayed titanium and hydroxyapatite support the maturation of microbial plaque with the successive inclusion of a variety of morphotypes. PMID- 8218745 TI - Tissue reactions towards titanium implants inserted in growing jaws. A histological study in the pig. AB - In this investigation, the tissue reactions towards titanium implants inserted in growing jaws of pigs were studied by means of histology. At the age of 12 weeks, 5 test pigs each received 4 Branemark System titanium implants (fixtures). The fixtures were inserted immediately after extraction of the mesial root of the second deciduous premolar (P2) and the deciduous canine (C) on one side of the mandible and the mesial root of the first deciduous premolar (P1) on the other side. The fourth implant was placed after extraction of the deciduous lateral incisor (L) on one side in the upper jaw. Furthermore, 1 pig in which no extractions or fixture installations were performed served as a control. All pigs were followed for 165 days with clinical, radiographic and biometric examinations, the results of which have been previously presented. In this study, 10-microns-thick ground sections were produced for histology after the jaws had been fixed by immersion in formalin and further processed and embedded in plastic resin. Six of the fixtures originally inserted were lost during the experimental period, and the remaining implants were found to be involved with mineralized bone to varying degrees. Regarding the fixture-to-teeth relationship, it was found that, in the premolar region of the lower jaw, the teeth were positioned superior to and buccally angulated in relation to the fixtures. In the upper jaw, the implants were positioned below the adjacent teeth but centrally in the alveolar process. Tooth germs adjacent to the fixture had a displaced eruption path, buccally or lingually to the fixture. If the bud developed in close contact with the fixture, a changed morphology of the germ could be observed. PMID- 8218746 TI - Endosseous titanium implants during and after orthodontic load--an experimental study in the dog. AB - An experiment was carried out to determine whether endosseous titanium implants (Branemark) retain their clinical stability throughout a 26-week period of continuously applied force (2 N) and what kind of marginal peri-implant bone changes occur in the process. For this purpose 6 premolars (P3: mandible/maxilla and P4: mandible) were extracted from each of 2 foxhounds, and 12 implants (6 per dog) were positioned in the edentulous maxillary and mandibular areas after the alveolar healing period. Following a 25-week implant healing period, 8 fixtures (P3 areas) were used as anchoring elements for distalization of the 2nd premolars over a period of 26 weeks; 4 implants served as a control group (P4 areas of the mandible). There were no clinical or histological signs of implant dislocation after the load application period. In the presence of mild peri-implant gingivitis, no increase was found in the incidence of marginal bone resorption adjacent to the loaded implants compared with the non-loaded implants. In the absence of marginal resorption, subperiosteal bone apposition was detected especially around the test implants in the mandible. This suggests that endosseous titanium implants are suitable as anchoring units for longer-term orthodontic tooth movements. The applied force may moreover induce marginal bone appositions adjacent to the implants. PMID- 8218747 TI - Anterior tooth replacement with implants in patients with a narrow alveolar ridge form. A clinical study using guided tissue regeneration. AB - Clinical and radiographic examination was used to select patients with a suspected need of guided tissue regeneration (GTR). Fifteen patients with 20 fixtures were included in the study. Nine (45%) of the fixtures were completely covered with bone at fixture surgery and no GTR was required in these cases. On the remaining 11 fixtures, one or more sites were exposed and thus an expanded polytetrafluoroethylene membrane was used. The regenerative results were assessed using 2 methods, a) calculation of exposed threads in the mouth and on projected colour slides, b) photometric evaluation of exposed area. In total, the membrane group showed a bone gain of 81% when threads were calculated. Almost complete agreement in percentage of bone gain was observed between buccal (80.7%) and lingual (82.6%) sites. Photometric evaluation for the buccal sites showed a bone gain of 74%. Complete bone regeneration (100%) was achieved when healing was free from complications and also under an exposed membrane when infection was absent. The results indicate that the membrane technique is highly successful for treatment of exposed implants when healing is free from complications. It also shows that clinical and radiographic examination is not precise enough to differentiate between those patients planned for routine fixture surgery and those with a supplementary need for GTR. Thus access to GTR technique is important when treatment is planned for borderline cases. PMID- 8218748 TI - On clinical loading of osseointegrated implants. A methodological and clinical study. AB - Strain gauges were used to record in vivo and in vitro functional deformations in a fixed prosthetic appliance supported and retained by osseointegrated titanium implants. Four linear gauges were attached to each of totally 5 implant abutment cylinders and gauge signals were transferred into a computer via a digital converter. A computer program (ASYST) was used for collection, calibration and analysis of data obtained. Based on the results of a series of explorative in vitro tests, in vivo experiments were performed at maximum biting as well as during chewing on certain normally available food items. The results show fundamental differences between in vitro and in vivo testing conditions. Unexpectedly high bending of the implants was recorded in many of the in vivo loading situations. PMID- 8218749 TI - Review article: Barrett's oesophagus--cancer risk, biology and therapeutic management. AB - Barrett's oesophagus is receiving increasing scrutiny as the rates of adenocarcinoma of the oesophagus rise. Because clinical features are not predictive of the presence of Barrett's oesophagus and most individuals with Barrett's oesophagus go undetected, a case can be made for surveillance endoscopy in patients with chronic reflux. Once Barrett's oesophagus is diagnosed patients should be entered into a surveillance programme despite lack of proof of efficacy. Scientific study of putative biological markers of increased risk has added dramatically to the understanding of the biology of the lesion, but currently the finding of high grade dysplasia remains the best marker predicting the presence of greatly increased risk of developing cancer. It is likely that newer molecular biology techniques will become clinically applicable biological markers in the future. Currently there is no effective medical nor surgical therapy to cause regression of the metaplastic Barrett's epithelium, however the application of novel de-differentiating agents or ablation of the metaplastic epithelium while controlling oesophageal acid exposure and other environmental abnormalities offer hope that effective treatment of Barrett's oesophagus may someday be reality. PMID- 8218750 TI - Review article: endoscopy-related infections. AB - Endoscopic procedures generate bacteraemia to different degrees. Under certain conditions, most notably valvular heart disease, clinically significant infections may occur. A large body of literature has grown around recommendations for antibiotic prophylaxis to prevent procedure-related infections. Most of this literature is in the form of anecdotal reports. Few prospective randomized studies have been performed. In this paper, the literature on endoscopy-related infections is reviewed. Recommendations for antibiotics from different sources are compared and a rational approach to prophylactic antibiotic therapy is presented. PMID- 8218751 TI - Review article: thromboxanes in inflammatory bowel disease--pathogenic and therapeutic implications. AB - Recent work suggests that thromboxanes may play a major pathogenic role in inflammatory bowel disease. Thromboxanes are produced in excess not only in inflamed mucosa but also in Crohn's disease, by uninflamed bowel and by isolated intestinal and peripheral blood mononuclear cells. Their cellular source is likely to include platelets, neutrophils, endothelial and epithelial cells as well as mononuclear cells, possible stimuli to their overproduction being chemotactic peptides, lipopolysaccharide, leukotrienes, platelet activating factor, interleukin-1, bradykinin and angiotensin II. The pro-inflammatory effects of thromboxanes are both direct (diapedesis and activation of neutrophils, mucosal ulceration, reduction of suppressor T-cell activity) and indirect (vasoconstriction, platelet activation). Although corticosteroids and aminosalicylates inhibit thromboxane synthesis, this action does not necessarily explain their therapeutic effect in inflammatory bowel disease. Selective thromboxane synthesis inhibitors and receptor antagonists, however, ameliorate experimental colitis in animals. Picotamide and ridogrel are dual thromboxane pathway blockers already used in man. Drugs of this type could prove useful not only for the prevention of systemic thrombo-embolism but also for suppressing intestinal mucosal inflammation in patients with inflammatory bowel disease. PMID- 8218752 TI - Relapse rate of patients after healing of oesophagitis--a prospective study of alginate as self-care treatment for 6 months. French Co-operative Study Group. AB - In order to estimate the rate of symptomatic relapse and to identify factors associated with this relapse, 1030 patients were included in a multicentre study. All patients included had clinically and endoscopically healed oesophagitis (grade I (erosion, 57%), grade II (confluent erosion, 33%) or grade III (circular erosion, 9%)) after treatment with an H2-blocker or omeprazole. Patients were given conservative advice and were told to take sodium alginate only in response to pain. Relapse was defined as pain justifying more than eight sodium alginate sachets over 48 hours or treatment with another drug, or the need for a new endoscopy. Forty risk factors were recorded initially and patients were seen every 2 months; they filled out diary-cards describing symptoms and drug consumption. Data were available for 883 patients during follow up. The cumulative percentage of patients without relapse at 6 months estimated by Kaplan Meier method was 76 +/- 2% (mean +/- S.E.M.). Among these patients without relapse, 95% took less than two sachets per day. Only two factors were identified as associated with relapse--the grade of oesophagitis (P < 0.007), and the occurrence of stress during follow-up (P < 0.05). The percentage of patients free from relapse at six months was 85 +/- 2% in patients with grade I oesophagitis, 69 +/- 3% in patients with grade II, and 56 +/- 6% in patients with grade III oesophagitis (P < 0.0001). PMID- 8218753 TI - Effects of indomethacin on intragastric pH and meal-stimulated serum gastrin secretion in rheumatoid arthritis patients. AB - The effects of oral indomethacin on intragastric pH and serum gastrin were investigated in rheumatoid arthritis patients. Nine patients (1 male, 8 female) without a history of peptic ulcer disease and 6 patients with a history of peptic ulcer disease (5 male, 1 female) were studied. To obviate Helicobacter pylori infection as a confounding factor, only patients with positive H. pylori serology were included. After a 5-day period of placebo treatment and after a 5-day period of indomethacin (50 mg t.d.s.; total dose 750 mg), 24-h intragastric pH and basal and meal-stimulated serum gastrin levels were measured in a double-blind placebo controlled cross-over study. There were no differences in the median 24-h pH values between placebo and indomethacin users irrespective of peptic ulcer disease history. Indomethacin resulted in a higher basal and stimulated gastrin response than placebo in patients with a history of peptic ulcer disease. The basal and incremental responses were lower in patients with a history of peptic ulcer disease than in patients without a history of peptic ulcer disease, both during indomethacin and placebo. The same basal and stimulated incremental serum gastrin responses were found during placebo and indomethacin treatment in patients without a history of peptic ulcer disease. No correlation was established between median 2-h post-prandial intragastric pH and post-prandial incremental serum gastrin concentration. We conclude that indomethacin does not influence the intragastric pH of rheumatoid arthritis patients irrespective of history of peptic ulcer disease. PMID- 8218754 TI - Pharmacokinetics of budesonide enema in patients with distal ulcerative colitis or proctitis. AB - Pharmacokinetic data obtained after one dose of a 2-mg budesonide enema were compared with data obtained after the last dose of four weeks of daily treatment in 24 patients with active distal ulcerative colitis or proctitis. This open multicentre study involved 28 eligible patients. Sigmoidoscopy and biopsy scores improved significantly (P < 0.002) during the four-week treatment period. Maximal plasma concentration (Cmax) of budesonide was 2.1 nmol/L 1.3 h after the first dose and 2.5 nmol/L 1.2 h after the last dose; the difference was not significant. The area under the curve (AUC) of plasma concentration vs. time was after the first dose 9.7 nmol h/L and after the last dose 11.6 nmol h/L (P < 0.03). The small increase in AUC may be attributed to improved absorption. During the last dose interval, minimal plasma concentration was below the limit of quantitation in most subjects. The Cmax and AUC of budesonide increased slightly after four weeks of treatment, but budesonide did not accumulate. Mean morning plasma cortisol values did not change significantly during treatment (P = 0.083), although a small change in cortisol levels between the first visit (pre treatment) and last visit was positively correlated to the Cmax of budesonide measured at the last visit (P = 0.012). PMID- 8218755 TI - Two different dose regimens of cisapride in the treatment of reflux oesophagitis: a double-blind comparison with ranitidine. AB - We conducted a double-blind study comparing two dosage regimens of a prokinetic drug, cisapride (10 mg q.d.s. and 20 mg b.d.), with a low dose of a H2-receptor antagonist (150 mg ranitidine b.d.) in the treatment of 155 patients with reflux oesophagitis as determined by endoscopy. The active treatment took 8 to 12 weeks depending on whether complete healing was found at endoscopy. Improvement in oesophagitis grades from baseline to endpoint was observed in 68% of patients in the 10 mg cisapride q.d.s. group, 83% in the cisapride 20 mg b.d. group and 81% in the ranitidine group (N.S.). At endpoint, the percentages of endoscopically cured patients with initial grades I or II were 52% for 10 mg cisapride q.d.s., 71% for 20 mg cisapride b.d. and 80% for ranitidine (N.S.). The proportional improvement of the overall reflux symptom score (60%) also showed no significant difference between the three groups. In the treatment of mild reflux oesophagitis (grades I and II) similar results can be expected from 20 mg cisapride b.d. and 150 mg ranitidine b.d. As the results of the two dosage regimens of cisapride were not different, the 20 mg twice daily regimen is preferred because it will improve patient compliance. It is concluded that in reflux oesophagitis grades I and II, the efficacy of 20 mg cisapride b.d. and 150 mg ranitidine b.d. are broadly similar. PMID- 8218756 TI - Anti-secretory effects and pharmacokinetics of low dose ranitidine. AB - The purpose of this study was to examine the anti-secretory effect of low doses of orally administered ranitidine on meal-stimulated gastric acid secretion and assess its pharmacokinetics. The effect of 20, 40, 60 and 80 mg of ranitidine p.o. and placebo were tested on 5 separate days (Latin square, double-blind) in 15 healthy males (mean age 35 years). Gastric acid secretion was measured prior to and for 8 h following two sequential mixed liquid meals administered at 4-h intervals. Venous blood samples were obtained at frequent intervals before and following each dose for determination of plasma ranitidine concentration by high pressure liquid chromatography. Each dose of ranitidine significantly (P < 0.01) decreased the peak and cumulative 4-h acid secretory responses to the first meal (range 58-93%), and the 60 and 80 mg doses significantly inhibited the response to the second meal by 31 and 43%, respectively. Total 8-h meal-stimulated acid outputs were decreased significantly in a dose-related manner (range 38-73%). Peak plasma ranitidine occurred approximately 1 h after dosing. Ranitidine tmax, t1/2 and clearances were independent of dose; however, AUC and Cmax were dose related. Inhibition of acid secretion was related to plasma ranitidine concentration; the mean IC50 was 27 (+/- 6.4) ng/ml. We conclude that modest doses (equivalent to 7-27% of the daily therapeutic dose) of ranitidine effectively suppress meal-stimulated gastric acid secretion in a dose-related manner. If these doses are of clinical efficacy, it may be possible for substantial cost savings to occur. PMID- 8218757 TI - Exocrine pancreatic secretion in man following one week of M1-muscarinic receptor blockade. AB - A double-blind, randomized, placebo-controlled crossover study was performed to assess the influence of one week of selective M1-muscarinic receptor blockade on pancreatic exocrine secretion in man. Ten healthy subjects received telenzepine (3 mg p.o.) and placebo each for 8 days, with a 6-day drug-free washout interval between treatment sequences. On Day 8 of each sequence, pancreatic secretion was stimulated for 2 h by infusion of submaximal secretin (0.2 U.kg/h) followed by maximal stimulation with secretin (1.0 U.kg/h) and ceruletide (120 ng.kg/h). Telenzepine had no significant effect on secretory parameters during submaximal stimulation with secretin. During maximal stimulation, total protein, secretory volume, and output of amylase, trypsin and bicarbonate were unexpectedly increased by telenzepine. These findings might be partially explained by removal of the inhibitory influence of pancreatic polypeptide, which was depressed by telenzepine. Acute studies have shown that M1-receptor antagonists inhibit exocrine secretion. Our results suggest that adaptation of physiological mechanisms governing the exocrine pancreas may occur after one week of receptor blockade by a therapeutic dosage of telenzepine, to the extent that M1-blockade no longer inhibits secretion. PMID- 8218758 TI - Omeprazole versus famotidine in the healing and relapse of duodenal ulcer. AB - Sixty patients with symptomatic duodenal ulcer were randomized to receive either omeprazole (20 mg each morning) or famotidine (40 mg at night time) for 2-4 weeks in a double-blind parallel group clinical trial. Healing rates were higher with omeprazole in comparison with famotidine after 2 weeks (77% vs. 40%, P < 0.001) and 4 weeks (93% vs. 80%, P = 0.2) of treatment. Assessment of daily diary cards completed by all patients revealed that omeprazole rapidly relieved ulcer-related day pain and nocturnal pain in comparison to famotidine. Treatment with omeprazole for 2 weeks was also associated with lower cumulative antacid intake (P < 0.05) and reduced absenteeism from work. Helicobacter pylori infection was present in all patients and remained unaffected by treatment with either of the drugs. None of the drugs produced any significant adverse effects. During 6 months follow-up of all the patients after ulcer healing (without maintenance therapy), ulcer relapse was seen in 40% of omeprazole- and 37% of famotidine treated patients (P > 0.1). The duration of ulcer-free period following initial healing of ulcer was also similar in both the groups (median time: 22 weeks for omeprazole, 21 weeks for famotidine). We conclude that omeprazole is superior to famotidine in rapidly healing duodenal ulcers and achieving more rapid pain relief, but does not influence subsequent ulcer relapse. PMID- 8218759 TI - Comparison of two intravenous ranitidine regimens in a homogeneous population of intensive care unit patients. AB - Primed continuous infusion and repeated intravenous injections of ranitidine (daily dose 200 mg) were compared in a homogeneous population of post-operative intensive care unit patients in a randomized fashion. Intragastric pH was measured continuously for 72-96 h with combined glass electrodes positioned in the gastric corpus. Patients whose intragastric acidity fell below pH 4.0 for 70% of a 24-h period within 48 h after the operation (baseline period) were considered 'at risk' of developing stress-related lesions. From the 26 patients screened, 18 fulfilled this criterion. Nine received the continuous infusion regimen (50 mg bolus + 0.125 mg.kg/h) and nine received repeated boluses (50 mg ranitidine every 6 h). A consistent decrease of intragastric acidity was shown in each group by a rise in 24-h median pH from 1.4 (1.3-1.7; 26th-75th percentile) during the baseline period to 4.2 (1.9-5.4, P < 0.01) for the continuous infusion and from 1.55 (1.1-2.2) to 2.65 (2.1-3.5, P < 0.02) for the repeated boluses during the final 24 h of the therapy period. During that period intragastric pH was maintained above 4 for 52% of time by continuous infusion and for 40% of time for repeated boluses compared with 10.8% (P = 0.01) and 6.2% (P = 0.008) of time, respectively, in the baseline period. In conclusion, although no statistically significant differences between the two regimens could be detected, the continuous infusion regimen tended to show slightly better results in percentages of time that pH values were above 1 to 7, and in median 24-h pH values. PMID- 8218760 TI - Effect of treatment with liu-jun-zi-tang (TJ-43) on gastric emptying and gastrointestinal symptoms in dyspeptic patients. AB - The effects of treatment with the Chinese herbal medicine Liu-Jun-Zi-Tang (TJ-43) on gastric emptying and gastrointestinal symptoms were investigated in 42 patients with chronic idiopathic dyspepsia. By random allocation, 22 patients received oral treatment with 2.5 g TJ-43 three times daily, and 20 patients received placebo. Gastric emptying was measured by the acetaminophen absorption method. After 7 days of treatment, gastric emptying was significantly accelerated and gastrointestinal symptoms were significantly reduced in patients treated with TJ-43. Placebo treatment produced no significant effects. These findings indicate that TJ-43 had a prokinetic action on gastric emptying and that it was useful in treating chronic dyspepsia. PMID- 8218761 TI - Short report: treatment of Helicobacter pylori-associated duodenal ulcer with omeprazole plus antibiotics. AB - Omeprazole heals most duodenal ulcers after 4 weeks of treatment but relapse is common. Eradication of Helicobacter pylori is associated with reduced rate of ulcer relapse. This study investigates the effect of omeprazole with antibiotics in H. pylori-associated duodenal ulceration. Forty-three patients with endoscopically proven duodenal ulcer and H. pylori entered this study. Treatment consisted of 20 mg omeprazole daily (four weeks) and seven days (first week) treatment with 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. Four weeks after completing the treatment, 81% (35/43) had a healed duodenal ulcer, and 58% (25/43) had H. pylori eradication. In those who healed, at one year 21 remained H. pylori-negative, 12 had persistent H. pylori infection and 2 had re infection. The ulcer relapse rate at one year was 26%: of the 9 who relapsed, 6 had persistent infection, 2 were re-infected, and only 1 was H. pylori-negative. This combination therapy of antibiotics with omeprazole successfully eradicates Helicobacter pylori and has a lower ulcer relapse than omeprazole alone. PMID- 8218762 TI - [The emergency service at public hospitals. The need for change in Hospital Emergency Services]. PMID- 8218763 TI - [Nosocomial urinary tract infections in patients with prolonged bladder catheterization: un unsolved problem]. AB - Urinary tract infection (UTI) is the primary cause of hospitalary infection. We have prospectively studied during a 8-month period, 94 episodes of UTI in 61 patients with a mean age of 77 years and with a high percentage of vesical sounding (70.5%). The most frequent cause of sounding was urinary incontinence (74%) and in just 15% of all cases, there was a strict urological indication. The association fever/sounding was statistically significant (p < 0.05) and, when analyzing the prognosis factors, we observed that patients who had a significantly higher risk were those with vesical sounding (p < 0.05), fever equal to or higher than 38 degrees C and/or Pseudomonas aeruginosa isolated in their uroculture (p < 0.01). Among the microorganisms isolated, P. aeruginosa ranked in first place, followed by E. Coli. The most sensitive antibiotics in these patients were the aminoglycosides (tobramycin or gentamycin), cephtacidime and aztreonan. Finally, the percentage of coincidence between the microorganisms isolated in the uroculture and in the infections of other patients sharing the same room is significantly higher (p < 0.01) in patients with vesical sounding than in patients without it, suggesting a transmission role of the health staff. PMID- 8218764 TI - [Metoclopramide versus cinitapride in the treatment of functional dyspepsia]. AB - In 20 patients with diagnosis of functional dyspepsia due to dysmotility and/or reflux, the effectivity and tolerance of two prokinetic drugs--metochlopramide (MCP) (10 mg. three daily doses, vo) and cinitrapide (CTP) (1 mg., 3 daily doses, vo)--were assessed using a protocol of a propective and cross-sectional study after a blank period. Following the treatment with MCP and CTP, statistically significant improvements were observed in the intensity/severity of postprandial epigastric fullness, flatulence, epigastralgia, pyrosis, active regurgitations and anorexia. The MCP was more effective for the improvement of vomiting in these patients; however, the number of defecations per week increased significantly only after the CTP therapy. The therapeutical effectivity of both drugs, according to a subjective and objective global assessment was similar, with good results of 60-65% for MCP and 55-60% for CTP. Tolerance of both drugs was good. None of the patients spontaneously referred to the presence of side effects and only 3 patients (15%) treated with MCP and 2 patients (10%) treated with CTP mentioned some of the suggested side effects, which were absent before the onset of treatment. Both drugs produced an increase in the levels of Prolactine, but their average values were within the normal range. Only in two patients treated with MCP and in one patient treated with CTP, values slightly higher than the upper normal limit were observed. No significant differences were observed when comparing the results obtained with MCP therapy and CTP therapy. PMID- 8218765 TI - [Morbidity, mortality and other indicators of health care activities, at a General Internal Medicine Service]. AB - More than 50% of all health care expenses are incurred in hospitals, without objectively knowing many times their actual performance. Identification, sex, age, admission channel, date of admission, date of discharge, diagnosis and destination were recorded at discharge for all a local hospital. During those years, 6,410 patients were admitted in such Service (60.18% men and 39.18 women), with an average age of 63 years: 75% of all cases were emergencies, the average length of stay was 3.8 days and the occupation rate, 97.2%. 2.62% patients were referred to another center. The most frequent disease were cardiovascular (24.6%), respiratory (21.6%) and digestive (16.9%). The most frequent nosological entities were: chronic obstructive pulmonary disease (12%), acuter strokes (6.3%), cardiac failure (6.5%), ischemic cardiopathies (6.5%), high digestive hemorrhage (5.6%) and pneumonia (4.3%). The most frequent malignant tumors were those affecting lung, rectum-colon and hematologic. The average mortality rate was 4.3%, mainly due to malignant tumors and acute strokes. Diabetes mellitus and arterial hypertension were the most frequent associated diseases. PMID- 8218766 TI - [Nitrendipine in the treatment of mild-moderate essential arterial hypertension. Ambulatory study in Primary Care]. AB - A non-comparative open clinical pharmacological surveillance study was conducted, in which 427 patients from both sexes with diagnosis of light to moderate essential arterial hypertension were included. All patients were treated with nitrenpine, a dihydropyridinic calcium antagonist during a 28-week period. The initial dosage was 10 mg/day, increasing such dosage to 20 and 40 mg/day and associating it with a thiazidic diuretic in those patients showing no antihypertensive response (diastolic arterial pressure (DAP) of 90 mmHg or a reduction of 10 mmHg in baseline figures). A significant decrease was observed in systolic arterial pressure (from 159.3 +/- 12.6 to 149.2 +/- 12.2 mmHg) and in Dap (from 94.8 +/- 9.6 to 86.7 +/- 10.5 mmHg), p < 0.001, with effectivity in 66.3% of patients (65% receiving monotherapy; 10.3% combined therapy: nitrendipine and diuretic). No modifications were observed in heart rate nor in the biological-metabolic parameters under study. Side effects had a low incidence (15.9% of patients, with a 4.7% of drop-outs) and were well-tolerated in most cases. Given these results, we can conclude that nitrendipine is an effective and safe drug for the treatment of light to moderate arterial hypertension. PMID- 8218767 TI - [Angio-invasive disseminated aspergillosis: autopsy diagnosis in leukemic patients]. AB - We report on two patients with acute lymphoblastic leukemia in induction chemotherapy, who developed a sepsis which led, in both cases, to death following the appearance of neurological symptoms suggesting CNS affectation. Autopsy revealed an angioinvasive disseminated aspergillosis affecting lungs, brain, myocardium, kidneys, thyroid glands in both cases, and endocardium, urinary bladder, lymph nodes, alimentary tract, nasal sinuses in one of the cases. Microbiology study of necropsic tissue showed Aspergillus flavusoryzae and likewise Candida albicans in one case. The latter finding suggest a combined fungal sepsis caused to candida and aspergillus. PMID- 8218769 TI - [Bronchiolitis obliterans with organizing pneumonia]. AB - We present a typical case of Obliterant Bonchilitis with Organizative Pneumonia in a 73-years-old man. The diagnosis was established through minithoracotomy. Treated with high dosage of methylprednisolone, the clinical-radiological evolution was satisfactory. It is very important to know and correctly diagnose this entity, given its excellent therapeutical response. PMID- 8218768 TI - [Erythroderma caused by carbamazepine. Diagnosis with skin patch]. AB - We present two cases of cutaneous erythroderma induced by carbamazepine therapy, both cases with just cutaneous affection and only one suspicious drug. A cutaneous patch study, with standard battery from the Spanish Contact Dermatitis Research Group, vaseline with carbamazepine at 10% and lectures at 48 and 96 hours, was conducted. The result was positive for carbamazepine and negative for all other patches in both cases. All controls were negative. This is a very simple test, easy to perform, specific and with low side effects, allowing the diagnosis of this pathology. PMID- 8218770 TI - [Pseudometastatic hepatic lesions and Kikuchi necrotizing lymphadenitis]. AB - Kikuchi's necrotizing lymphadenitis (KNL) is a benign disease of unknown etiology affecting lymphatic nodes and some times extranodal organs. We present a case of KNL with hepatic lesions simulating metastatic liver disease. PMID- 8218771 TI - [Fatal poisoning with paraquat: report of a new case]. AB - Intoxication with paraquat has been rarely described in our country. We present a case of a 66-years-old man admitted to our hospital five hours after an accidental ingestion of a sip of paraquat. Despite therapy with gastric lavage, Fuller's Soil, Magnesium Sulphate, liquids and hemoperfusion, the patient developed Multiple Organic Failure and died 48 hours after his hospitalization. Plasmatic levels of the herbicide were very high. Typical clinical data, prognosis factors and therapeutical management of this intoxication are described. PMID- 8218772 TI - [Education strategies in the therapy of asthma]. AB - Bronchial asthma is a disease whose incidence has increase over the past years despite the effectivity of the pharmacological therapy. The relevant role of education in the control of asthma has been stressed for a long time. The knowledge by the patients and their relatives of the trigger factors, the clinical manifestations of asthma and the relationship between symptoms and severity of the disease and the decision making by the patients their selves in order to self-modified the therapy without the need to consult with the physician. This kind of educational program has shown to be very useful in order to maintain a more strict control of the disease and, despite their financial cost, the have a favourable cost-benefit ratio due to the reduction in the number of hospitalized patients and lenght of stay. PMID- 8218773 TI - [Idiopathic pulmonary fibrosis: new diagnostic and therapeutic perspectives]. AB - Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology affecting alveolo-interstitial structures. It is clinically characterized by progressive dyspnea and dry cough. In the physical exploration, crakles at the pulmonary bases and acropachies are usually detected. Its diagnosis has been a major clinical problem. Currently, a definitive diagnosis can be established with high resolution computerized axial tomography, bronchoalveolar lavage and open pulmonary biopsy. The next clinical problem is the assessment of activity, since it allows to differentiate subsidiary patients for receiving treatment. The description of new therapeutical alternatives has brought new perspectives in the management of these patients. Corticotherapy associated to immunosuppressors has allowed to reduce side effects and to obtain dramatic improvements. Lung transplantation, currently under study, will be the therapy of the future. PMID- 8218774 TI - [Sleep, chemoprophylaxis, and vomit]. PMID- 8218775 TI - [Severe hyponatremia caused by inappropriate antidiuretic hormone secretion syndrome. Infrequent complication of mediterranean boutonneuse fever]. PMID- 8218776 TI - [Effectiveness of captopril in systemic lupus erythematosus with HTA in primary care]. PMID- 8218777 TI - [Multiple myeloma and adenocarcinoma liver metastasis]. PMID- 8218778 TI - [Limitations of the albumin sero-ascitic gradient]. PMID- 8218779 TI - [The option of etidronate in the treatment of osteoporosis]. PMID- 8218780 TI - [Detection and clinical course of metabolic multiple vascular risk syndrome]. AB - The potential associations between the factors making up the vascular multi-risk metabolic syndrome (VMMS) or syndrome X (hypertension, diabetes, lipidic disorders, hyperinsulinemia and obesity) are studied: a) in patients with recent cerebral infarct or acute myocardial infarct; b) in patients hospitalized for the management of their hypertension, diabetes or obesity; c) at two years of evolution since the initial diagnosis of hypertension, diabetes or obesity. The results confirm that the VMMS, either complete or incomplete, is detected starting from the clinical management of any of its components (hypertension, diabetes, obesity) or complications (cerebral or myocardial infarct). These results and the ones regarding the evolution at two years of the risk factors associations, allows a discussion of the physiopathologic reality of the VMMS as an entity or a causal association. PMID- 8218781 TI - [Polyglobulia and bronchopneumopathies: correlations of ferritin and other ferric parameters with various erythrocytic indexes]. AB - In 15 patients with chronic bronchopneumopathy (7 with polyglobulia and 8 without it), we observed that polyglobulic patients had higher average levels of sideremia and basal saturation of transferrin and lower levels of HCM, CHCM and VCM. No significant differences were observed in the average levels of ferritin between both groups. Overall, in this series of 15 patients, a significant inverse correlation was observed between sideremia and HCM (r = -0.52; p < 0.05) and between sideremia and CHCM (r = -0.55, p < 0.5), as well as a trend towards a direct correlation between sideremia and the red blood cells count (r = 0.45, N.S.). There was also a direct correlation between serum ferritin and the sedimentation rate (r = 0.72, p < 0.01) and trends towards inverse correlations although not significant, between ferritin and sideremia (r = -0.25, N.S.). These data reflect a hyperconsumption of iron in the respiratory polyglobulia, with some relative deficit, suggesting as well that serum ferritin is not a good enough criteria in these cases for the evaluation of iron deposits, because it behaves like the sedimentation rate with respect to acute phase reactants when there is inflammation. PMID- 8218782 TI - [Pulmonary tuberculosis: differences between patients seropositive and seronegative for the acquired immunodeficiency virus]. AB - 423 cases of pulmonary tuberculosis (PT) are described, dividing them into two major groups depending on the presence (Group 1:54 cases) or the absence (Group 2:369 cases) of infection by the Acquired Immunodeficiency Virus, in order to compare their clinical-epidemiological characteristics. 70.37% patients of Group 1 had an age between 15 and 30 years and 72.2% (39 cases) were parenterally drug addicts. In the Group 1, fever, general and digestive symptoms were predominant (p < 0.004, p < 0.01 and p, 0.00001); a miliar profile was observed in 8 cases (14.8%) and the radiology was normal in 7 cases (12.9%), with predominance of condensation semiology and cavitation in Group II (p < 0.003 and p < 0.00001). In addition, we observed extrapulmonary affection in 42.6% cases (23 patients) of Group I (p < 0.0004) and the diagnosis of tuberculosis determined the presence of AIDS in 26 cases (48.1%). PMID- 8218783 TI - [Evaluation of a combination of a diuretic and nifedipine retard for the treatment of hypertensive patients refractory to nifedipine retard]. AB - This study assessed the effectivity of the association between a diuretic, chlorthalidone, and retard nifedipine in the treatment of patients above 50 years of age with Arterial Hypertension refractory to retard nifedipine. A prospective study of a 3-month controlled intervention was designed, in which the patients were treated with retard nifedipine for 2 months and, if they did not respond to the treatment, chlorthalidone was associated for 1 month. Out of 235 patients selected at the beginning of the study, 28 dropped out voluntarily, 24 were excluded because they did not adhere to the protocol and 30 dropped out due to side effects. After the first two months of therapy, hypertension was controlled in 60.2% of the 181 patients, whereas in the third month, only in 20% of the 44 patients considered could be controlled. Significant differences were observed between the two treatments (p < 0.001) with a 95% CI in the percentage differences of 54% versus 26.4%. These results suggest that the association of chlorthalidone and retard nifedipine does not improve the treatment of Arterial Hypertension refractory to retard nifedipine. PMID- 8218784 TI - [Chronic autoimmune type II hepatitis with various extrahepatic clinical manifestations]. AB - We present the case of a patient with autoimmune chronic hepatitis and anti-LKM antibodies, who developed associated autoimmune diseases, cyclic nodose erythema, bilateral peripheric paralysis, idiopathic thrombocytopenic purpura and diabetes mellitus. We describe the first signs of the disease and how three different forms can be differentiated depending on the type of autoantibodies present in the patients' serum. Finally, we list several forms of presentation of the disease, the potential clinical associations with other autoimmune processes and the potential immunological basis for the development of the hepatic lesion. PMID- 8218785 TI - [Seronegative systemic lupus erythematosus and autoimmune thyroiditis]. AB - The association of systemic lupus erythematosus (SLE) and autoimmune thyroiditis has been previously described. We report a woman with negative antinuclear antibodies (ANA) and criteria for the diagnosis of SLE. The patient was also diagnosed with autoimmune thyroiditis. We review the clinical characteristics and the association of both entities. We also remark in this case the association of autoimmune thyroiditis with seronegative SLE. PMID- 8218786 TI - [Focal and segmentary necrotizing glomerulonephritis in rheumatoid arthritis. Description of 2 cases]. AB - Two patients diagnosed of seropositive Rheumatoid Arthritis, developed severe renal failure associated in one case to alveolar hemorrhage. The renal histological study showed in both patients Focal and Segmentary Necrotizing Glomerulonephritis, with extracapillary proliferation. There were no evidences of concomitant diseases or nephrotoxic pharmacological therapy in the two patients. The first patient had a positive response to the corticosteroid and immunosuppressive therapy, whereas the second patient developed an irreversible renal failure. We think that this complication, although extremely rare, must be taken into account in all patients with Rheumatoid Arthritis presenting a quick and sudden impairment of his renal function. PMID- 8218787 TI - [Tuberculosis as risk factor for venous thrombosis]. AB - Over a 2-year period, 3 patients with deep venous thrombosis associated to advanced pulmonary tuberculosis have been observed. One of them died suddenly, probably due to thromboembolic complications. In the other two cases, a triggering factor of venous thrombosis, probably related to tuberculosis, was detected and their evolution was satisfactory. The high frequency of antiphospholipid antibodies detected in the tuberculosis and the potential relationship between these and deficit of protein S is mentioned. Advanced pulmonary tuberculosis is described as a risk factor for the development of venous thrombosis in patients with negative serology for human immunodeficiency virus type 1 and 2. We recommend not to use deep venous catheters and we stress the potential value of heparin prophylactic therapy in order to prevent venous thrombosis and its complications. PMID- 8218788 TI - [Hyperthyroidism as a cause of irreversible dilated myocardiopathy]. AB - We describe the case of a young man with Graves Basedow's Disease as the unique cause of congestive heart failure, which after several months of antihyperthyroid therapy not very strictly followed, underwent heart transplantation due to severe ventricular and diastolic disfunction. The relationship between thyroid hypertension and cardiomyopathy is reviewed. PMID- 8218790 TI - [The borderlines --closed, open, or blurred-- of panmyelopathies]. PMID- 8218789 TI - [Asymptomatic microhematuria in the adult]. AB - There is some controversy with respect to the attitudes that should be adopted when microhematuria is detected in asymptomatic subjects. The prevalence of MH ranges from 1 to 13%. The diagnostic evaluations conducted by different study groups suggest that the most frequent lesions are (in decreasing order) prostatic benign hypertrophy, followed by urinary tract infections, urolithiasis and neoplasias. Reactive straps are useful for the detection of hematuria. If the test is positive, a microscopical exploration of the urinary sediment is recommended, because it will confirm the results and sometimes it will provide some information about the cause of bleeding. The clinical evaluation should start with a detailed basic blood and urine analysis and other analytical test, depending on the clinical suspicion. The structural study of the urinary tract should start with an intravenous urography and/or simple echography + radiography. Personal predilections and the medical setting will be the major factors determining the election of one or other type of exploration. If after the first diagnostic study, the cause of hematuria is still unknown, there is no need to repeat again such study. Just in case of developing some symptomatology, the strategy to follow should have to be reconsidered on an individual basis. PMID- 8218791 TI - [Disseminated lupus erythematosus and interstitial nephropathy]. PMID- 8218792 TI - [Warthin's tumor associated with generalized lymphadenopathy in a patient with HIV infection]. PMID- 8218793 TI - [Severe allergic reaction caused by cisplatin administration]. PMID- 8218794 TI - [Diagnosis and treatment of a bronchial carcinoid]. PMID- 8218795 TI - [Ehlers-Danlos syndrome and postoperative hematoma]. PMID- 8218796 TI - [The activation of the patient in his disease]. PMID- 8218797 TI - [Vascular explorations in the diagnosis of algodystrophy]. AB - We applied to a group of 44 patients, clinically affected by algodystrophy, a protocol of vascular explorations (Doppler, capillaroscopy, basal plethysmography, reactive hyperemia test and measurements of the oxygen transcutaneous pressure) in order to analyze their contribution to the detection of such disease, concluding that Doppler, capillaroscopy and plethysmography do not contribute with quantifiable results. On the contrary, the reactive hyperemia test and the measurements of the oxygen transcutaneous pressure showed up as explorations able to quantify the degree of microcirculatory disorder in the algodystrophy and to allow its evolutive follow-up. PMID- 8218798 TI - [An epidemiological study of tuberculosis in the health area of Santiago de Compostela during the years 1989, 1990 and 1991]. AB - In order to assess the incidence of tuberculous disease in our health area, we reviewed the clinical records of patients from the three hospitals of the area under study during the years 1989, 1990 and 1991, who had positive bacilloscopy, positive Lowenstein's culture in any specimen and/or compatible anatomopathologic report. After excluding 26 patients because they belonged to other health areas, 885 patients remained in the study, out of which 251 (64% men and 36% women) were from the year 1989, 270 (64% men and 36% women) from the year 1990 and 364 (62% men and 38% women) from the year 1991. The mean age was 38.4 (SD 20.5). Fifty-one percent of the patients were between 20 and 35 years old. The rate of new cases was 65.87 per 100.000 population in 1989, 71.05 in 1990 and 95.53 in 1991. Seventy-four cases were HIV-positive (8%). Tuberculous meningitis was present in 12 patients. The highest mortality was 1.79 per 100.000 population in 1990. We conclude that tuberculosis presents a medium-high incidence in our health area. PMID- 8218799 TI - [Bronchial carcinoma in the health area of Estella]. AB - Bronchial carcinoma (BC) is still a main health problem, being the most frequent neoplasia among men and the second most frequent among women. In order to update the epidemiological data of this pathology in our health area, we have retrospectively studied 24 patients in whom BC was diagnosed throughout a year among the population of the Health Area of Estella, a province of Navarra. The patients were included in a protocolized study for their biostatistical analysis with the aim of determining their distribution rate by ages, sex, risk factors, previous chronic pulmonary disease, initial symptoms, radiological results, diagnostic procedures, histopathology and stage of neoplasia. We conclude that, in general terms, our experience does not differ from other studies conducted in our country or abroad, although in demonstrates a significant increase in the incidence of BC in our health area during the past 10 years. PMID- 8218800 TI - [Does goiter constitute basically a surgical process?]. AB - Goiter is usually a clinical manifestation present almost in all the thyroid processes. The over-simple idea of a thyroid tumoration demanding surgical resection is, unfortunately, deeply implanted in many medical and, above all, surgical environments. We tried to estimate the incidence of goiter in a series of thyroid processes and how many of them required surgery. We reviewed the surgical indications in several thyroid entities. In a series of 377 thyroidopathies, goiter was present in 345 (91.5%), 50 of which underwent surgery (12.26% of the total and 14.49 of goiters). Some of the patients were operated in other hospitals without adjusting to the aforementioned criteria and, in theory, just 36 of then should had undergone surgery (9.54% of the total and 10.43% of goiters). In conclusion, surgery has a very secondary role in the treatment of goiter. PMID- 8218801 TI - [Miliary tuberculosis and cerebral tuberculomas. Apropos a case]. AB - We present a case of a 45-year-old patient with miliary tuberculosis (MI), whose initial clinical symptomatology was uncertain. A few weeks after the beginning of chemotherapy, and in the face a Jacksonian crisis, cerebral tuberculomas were detected with CAT. The interesting thing in this case is to highlight that the diagnosis of MT anatomopathologic after pulmonary biopsy with mini-thoracotomy and that the cerebral complication could be classified within the so-called "paradoxical worsening" as it has been documented in the literature. PMID- 8218802 TI - [Malignant pleural mesothelioma. A diagnostic and therapeutic challenge]. AB - Malignant pleural mesothelioma is a tumor very difficult to diagnose and with a very controversial therapy. We describe an illustrative case with development of pleural overflow and detection of high adenosine-deaminase levels. Surgical resection combined with radiotherapy and/or chemotherapy is the current therapeutics. We describe the state-of-the-art advances in the immunohistochemical diagnosis and therapeutics and we stress the need to conduct cooperative studies in order to achieve a better knowledge of the prognosis factors, an effective step-by-step approach and innovative therapy strategies. PMID- 8218803 TI - [Pericarditis due to Legionella]. AB - Legionellosis is a systemic infectious disease generally affecting the respiratory system. We present a case with repercussions just at the peri-cardiac level. We review the literature and the diagnostic methods. In addition, we discuss the physiopathological theories and we suggest the convenience of looking for this etiology in the cases of pericarditis. PMID- 8218804 TI - [Allergic granulomatosis as a systemic disease]. AB - The Churg-Strauss's allergic granulomatosis is an entity considered by some authors as a simple clinical problem within the context of vasculitis, but that given its anatomopathological and clinical characteristics (different from other vasculitis), must be studied as a separate syndrome. Its incidence depends on the strictness in the application of the diagnosis criteria and its pathogenic is unknown. Although the most frequent pathology is respiratory, we review the affectation of other organs and systems (circulatory, digestive, urogenital, locomotive, nervous system, skin, etc.), stressing the relevance of its knowledge for a correct diagnosis. The current therapy is based in seeking an useful drug, which added of the patients. of the patients. PMID- 8218805 TI - [The responses to notice of a death]. AB - A better understanding of the process of bereavement is important because assist to remove some negative stereotypes. There is no easy way to give news of death, and physicians and nurses receive little instruction in how to handle such situation. It is usually learned by on-the-job training. Ideally, the news should be conveyed by the physician who took care of the patient during the illness and who knows the surviving relatives well enough to be able to frame the news in a manner that anticipates the likely responses. PMID- 8218806 TI - [The prevention of thromboembolic disease in medical patients: heparin-calcium or low-molecular-weight heparin?]. PMID- 8218807 TI - [Congestive myocardiopathy in the Churg-Strauss syndrome]. PMID- 8218808 TI - [Marfan's syndrome. A case report]. PMID- 8218809 TI - [S. agalactiae-induced septic arthritis in a patient with vulvar carcinoma]. PMID- 8218810 TI - [Comparative studies of the 2 networks of primary care]. PMID- 8218811 TI - [Should the quality level of care delivered be measured?]. PMID- 8218812 TI - [Epidemiology of dyslipidemias in a general adult population of the basic health area "La Orden de Huelva"]. AB - OBJECTIVE: To find the prevalence of dyslipaemias in the general adult population. DESIGN: A crossover epidemiological study of a population base. SETTING: Primary Care. "La Orden" Health Centre, Huelva. PARTICIPANTS: 878 people over 19 chosen by random sampling stratified according to age and gender; obtained from the 1991 Municipal Census covering our Health area. MEASUREMENTS AND MAIN RESULTS: 802 people completed the study, which included a survey of demographic data, personal histories, cigarette consumption and recordings of weight, height, blood pressure, glycaemia, total cholesterol (TC), cHDL, cLDL, and triglycerides (TG). Prevalence of Hypercholesterolaemia (TC > 250) was 25.5% (CI 95%: 22.4-28.6); breaking down as 28.7% in men and 22.5% in women. Hypertriglyceridaemia (TG > 200) was 8.9% (CI 95%: 6.2-11.6); 15% in men and 3.2% in women. cHDL < 35 was 3.5% (CI: 2.2-4.8); 5.7% in men and 1.5% in women. cLDL > 150 was 43.6% (CI: 40.1-47.1%); 48.9% in men and 41.4% in women. Multiple linear regression showed links of TC and cLDL to age (p < 0.001). TGs increase in line with age, the Quetelet index (QI) and cigarette consumption (CC) (p < 0.001). cHDL diminishes in line with increases in the QI and CC (p < 0.0001). CONCLUSIONS: Given the high levels of dyslipaemias found, intervention measures must be based on the search for lipid disturbances in patients attending clinics as well as on strategies directed towards modifying hygiene-dietary habits, something necessary for over 70% of the population. PMID- 8218813 TI - [Review of the original articles published by primary care professionals in Catalonia]. AB - OBJECTIVE: To describe the characteristics of the research work published by Primary Care professionals in Catalonia between 1989 and 1991, with an analysis of the preferred research areas, design type and different bibliometric features, with the aim of finding what is the real state of Primary Care research in Catalonia. DESIGN: Descriptive study based on checking all the original articles published between January 1989 and December 1991 in nine Spanish journals in the Primary Care, internal medicine and paediatrics fields. SETTING: Included were studies carried out by Primary Care professionals in Catalonia, either working alone or in collaboration, and which were relevant to Primary Care. MEASUREMENTS AND MAIN RESULTS: A total of 63 articles were surveyed. The average number of authors per article was 5.8 +/- 2.4. The majority of the signatories were Family and Community Medicine (FCM) specialists. 65.1% of articles were by professionals from FCM teaching units. The most common research areas were epidemiology, clinics and prevention. 74.6% of the articles were descriptive. 69.8% used some technique of inferential statistics. The average number of bibliographical quotations was 18.9 +/- 10.4: with the journal Atencion Primaria the most quoted. CONCLUSIONS: This study revealed the type of research being undertaken in the Primary Care field in Catalonia. PMID- 8218814 TI - [Principal components analysis]. AB - OBJECTIVE: This study wants to identify factors or components latent besides health indicators from Spanish regions, and its graphic output. DESIGN: Observational study. SETTING: Twenty eight indicators from regions were used: mortality, morbidity, communicable and no-communicable diseases, diet, dwelling and sanitary resources. Measurement was made between 1980-1988. INTERVENTIONS: Principal component analysis has been applied to the indicators, reducing data dimension. MEASUREMENT AND MAIN RESULTS: Eight factors have been extracted, which explain 90% of the original information. This analysis, as can be seen from communnalities, represents correctly the set of original variables. The factors with more easily interpretation were: shortage sanitary resources, develop diet, mortality, chronic diseases and accidental. CONCLUSIONS: Only reduction data dimension could be justify the use of principal component analysis. Behind the agrupation of variables is mostly the socioeconomic background. PMID- 8218815 TI - [Factors related to community participation in primary care in the province of Toledo]. AB - OBJECTIVE: To identify how many professionals have, in their view, some experience of community participation (CP); how many have a positive attitude to CP; and other associated factors. DESIGN: Observational, analytic, crossover study. PARTICIPANTS: Professionals from 22 Health Centres (HC). INTERVENTION: A questionnaire on attitudes, knowledge and behaviour. MEASUREMENTS AND MAIN RESULTS: 220 (67%) of the 330 professionals who received the survey replied. More than half of these considered that CP in the HC was important. 49% had some experience of this question: of these 59% evaluated their experience was successful, a variable which was linked to work satisfaction, attachment to the HC for less than one year or more than five and being a nursing professional. The main problem was considered to be lack of preparation; and the main cause of failure of experiments was defective planning. 95% of professionals were willing to work on health projects involving community participation. CONCLUSIONS: Even accepting the difficulty of measuring attitudes, knowledge and behaviour, the idea and that the positive attitudes and/or experiences of Primary Care health professionals to CP are a chance phenomenon is rejected. An intervention study to check the hypotheses suggested in this study concerning the variable factors which favour success in community health participation is proposed. PMID- 8218816 TI - [Anxiety scales and Goldberg's depression: an efficient interview guide for the detection of psychologic distress]. AB - OBJECTIVES: Validation of Goldberg's Anxiety and Depression scales in our settings. DESIGN: Transverse study. Two phases screening at population previously stratified and randomly allocated. SITE. National Health Institute's Primary Care Centres at the city of Zaragoza. PATIENTS AND OTHER PARTICIPANTS: 444 patients, aged 19 and older, who attend their general practitioner for a new episode of illness. The sample has been previously stratified by sex and age. MEASUREMENTS AND MAIN RESULTS: At the first stage the sample has been studied with a Health Survey consisting of a variety of sound validity (General Health Questionnaire-28 items version, spanish version of Folstein's mini Mental Status Examination, CAGE and another drug and over the counter products screening questionnaire) and the new scales, that we attempt to validate. At the second stage "the possible cases" chosen at the first phase and 10% of possible non cases are assessed with a comprehensive Psychiatric Interview: EPEP (Standardized Polyvalent Psychiatric Interview). CONCLUSIONS: The new scales E.A.D.G. have supported their validity for the screening of the most prevalent psychiatric disturbances in primary care settings. Their validity for the screening of the most prevalent psychiatric disturbances in primary care settings. They have outstanding and promising advantages when compared to traditional methods: brevity, simplicity, discriminatory ability between anxiety and depression and usefulness as an interview guideline. PMID- 8218817 TI - [Orthopedic treatment of nocturnal acroparesthesias in primary care]. AB - OBJECTIVE: To report the experience gained from the systematic use of a splint immobilising at night the flexion or extension of the carpus of patients affected by nocturnal acroparaesthesiae. DESIGN: Descriptive, observational study. SETTING: Two urban Health Centres. PATIENTS OR OTHERS PARTICIPANTS: Twenty-two patients were studied. These were 6 men and 16 women who attended during the period from June 1991 and June 1992 because of nocturnal acroparaesthesiae in the area innervated by the median nerve. INTERVENTIONS: The treatment used was to immobilize with a splint the flexion and extension of the carpus during the night. After three weeks the results were evaluated. MEASUREMENTS AND MAIN RESULTS: Disappearance of the symptomatology occurred in 8 cases (36.4%). In 10 cases (45.5%), the intensity or frequency of the acroparaesthesiae lessened and in the remaining 4 (18.2%) the symptoms persisted. No significant differences in the therapeutic results could be shown when the patients were grouped in line with clinical or exploratory findings. CONCLUSIONS: On account of the absence of side-effects, its low cost and its being accessible and bloodless, we recommend this treatment as the initial model of therapeutic intervention in Primary Care, while other diagnostic and/or therapeutic possibilities are considered. PMID- 8218818 TI - [Reflex sympathetic dystrophy]. AB - OBJECTIVE: The description of three cases of reflex sympathetic dystrophy. DESIGN: Retrospective clinical observations. SETTING: Gotic basic Health Area, Barcelona. PATIENTS AND OTHER PARTICIPANTS: Two women and a man (aged 75, 65 and 56) with mechanical pain and inflammation in the extremities. Two of the cases had a case history of trauma. Radiological signs of mottled osteoporosis were observed in the affected extremities of all the patients. In one there was gammagraphic pick-up. They were diagnosed as suffering reflex sympathetic dystrophy. INTERVENTIONS: Rehabilitation, non-steroid anti-inflammatories and treatment with Calcitonin. MEASUREMENTS AND MAIN RESULTS: Clinical and complementary diagnostic trials. CONCLUSIONS: Describing the clinical presentation and the necessary complementary trials to be able to reach an early diagnosis of this illness, which provides a better prognosis. PMID- 8218819 TI - [Acquired pneumonias in the community of Andoain]. AB - OBJECTIVE: To discover the clinical-epidemiological characteristics of pneumonias in our community. DESIGN: Descriptive study. SETTING: Andoain Health Centre. PATIENTS AND OTHERS PARTICIPANTS: There were 8,862 people in the reference population. All the cases of acquired pneumonia in the community were recorded. This register included those diagnosed in the Health Centre and in Casualty Departments and hospitals where patients were referred, between June 1 1991 and September 30 1992. The inclusion criteria were: acute fever chart and/or acute respiratory infection accompanied by a radiological image of pneumonic condensation. INTERVENTIONS: The model treatment was 500 mg of Erythromycin at six-hourly intervals for 14 days. 500 mg of Cefuroxim every twelve hours was added in cases considered at risk. MEASUREMENTS AND MAIN RESULTS: A total of 97 pneumonias were recorded, which represented an incidence of 8.82 pneumonias per thousand inhabitants per year. 63% were male. The average age was 42 (SD 19.25). 83% were diagnosed at the Health Centre. One-third presented a recent viral infection. Half had some risk factor: tobacco use was the most common. Response to treatment was satisfactory. Five percent had some complication. No death was recorded. CONCLUSIONS: Pneumonia is a frequent cause of attendance at Primary Care centres. There are several clear clinical symptoms, a good response to treatment with Erythromycin and virtual absence of complications [corrected]. PMID- 8218820 TI - [Delay in caring for patients with precordial pain]. AB - OBJECTIVES: Estimate the differences in the time of arrival at the Intensive Care Unite (ICU) among patients with previous++ infarction versus first infarction ones. DESIGN: Transversal retrospective study. SETTING: General Hospital of Elche. PATIENTS AND OTHER PARTICIPANTS: 622 diagnosed of infarction between 1984 1990. MEASUREMENTS AND MAIN RESULTS: The sample was divided into two groups according to whether having previous infarction or not. In each patient we registered age, sex, initial killip, initial CPK, maximum CPK, year of admission and time from beginning of symptoms till ICU arrival. None of the groups we studied showed significant differences in which refers to times to arrival at ICU. Initial CPK was lower in those who had previous infarction (p = 0.023) (obtained at the emergency ward). CONCLUSIONS: We concluded that patients with previous infarction arrive at hospital before those first infarction (lower CPK in emergency ward), but assistance protocols even the elapsed time when arriving at ICU. We did not find any factors which joined with time value in a significant way. PMID- 8218821 TI - [The primary care physician facing Parkinson's disease: practical approach. Medical Counseling Committee of the Spanish Parkinson Association]. PMID- 8218822 TI - [Can fewer mistakes be published in fewer lines?]. PMID- 8218823 TI - [Ambulatory monitoring of arterial blood pressure in primary care]. PMID- 8218824 TI - [Hypothyroidism and muscular pathology]. PMID- 8218825 TI - [Mortality from acute respiratory infections and influenza (1976-1980)]. PMID- 8218826 TI - The effect of cyclophosphamide treatment on lymphocyte subsets in the nonobese diabetic mouse: a comparison of various lymphoid organs. AB - The nonobese diabetic (NOD) mouse is a model for human Type 1 diabetes mellitus. Pancreatic beta-cell destruction in NOD mice is mediated by an autoimmune process which can be accelerated by cyclophosphamide (CP). We studied the phenotype of lymphocytes from central, peripheral and regional lymphoid tissues in prediabetic NOD and C3H mice before and after a single large dose of CP. All lymphoid organs showed a greatly diminished cell number and most alterations appeared early after CP and were transient, but an aggressive insulitis was not seen in NOD mice until 14 d after injection. The pancreatic islets in C3H mice remained intact and were not infiltrated. NOD female mice, which are most prone to spontaneous and CP induced diabetes, exhibited the most unusual lymphoid kinetics after treatment with CP. Their thymus and spleen showed the least relative drop in total cell number and the most rapid rate of recovery. The thymus of these mice was also found to have an increased proportion of CD3+ thymocytes while CD4/CD8 double positive thymocytes decreased 7 d after CP. At 14 d after CP the number of IL-2R+ thymocytes had surpassed that of normal levels. The most dramatic observation was the rapid recovery and overshoot in the number of pancreatic lymph node cells of female NOD mice which coincided with aggressive insulitis. PMID- 8218827 TI - Restoration of an early, progressive defect in responsiveness to T-cell activation in lupus mice by exogenous IL-2. AB - Splenic T-cells from lupus strain (NZB/W F1, Mrl/lpr) mice lack the ability to respond to concanavalin A (Con A) by secretion of IL-2 and hence expression of IL 2 receptor and proliferation. These defects were found not only in an aged group (> 5 months) of mice in which obvious clinical 'SLE like' symptoms and elevated levels of serum autoantibodies were observed, but also in mice as young as 4-wk. We demonstrate here that the defective mitogenic activation of T-cells from lupus mice is due to the inability of T-helper cells to produce IL-2 and this defect can be restored by exogenous IL-2 in vitro. Con A-induced cell proliferation and IL-2 receptor expression on CD3+ cells from lupus mice occur only in the presence of exogenous IL-2, whereas normal T-cells from BALB/c and CBA control mice are activated by the mitogen and undergo complete cell cycling in the absence of exogenous IL-2, as they are able to secrete sufficient endogenous IL-2. The detection of impaired T-helper function in young lupus mice, before development of overt disease, and the reversible nature of the defect indicate that defective IL-2 activity may be fundamental to the mechanism of development of pathology in SLE. PMID- 8218828 TI - An immunohistochemical study on organized lymphoid cell infiltrates in fetal and neonatal pancreases. A comparison with similar infiltrates found in the pancreas of a diabetic infant. AB - Lymphoid cell infiltrates were analyzed using immunohistochemical techniques on 5 normal fetal and 6 normal neonatal pancreases. Data were compared to data obtained analyzing the lymphoid cell infiltrates in the pancreas of an 8 months old diabetic infant. In the normal fetal and neonatal pancreases islets were intact and not infiltrated. In the diabetic infant beta-cells had vanished in almost all islets, the remaining islets showed a minor infiltration with primarily T-cells, a few B-cells, and some classical macrophages. It appeared that a widespread infiltration of the exocrine pancreas with single dendritic like cells, and T-cells, and little clusters of these cells were normal features of fetal and neonatal pancreases. In the diabetic case these infiltrative patterns were more pronounced. Larger accumulations of such lymphoid cells could also be detected in the normal fetal and neonatal pancreases and these consisted mainly of T-cell zones, sometimes containing HEV's, with intermingled interdigitating dendritic cells and a few macrophages. This architecture is reminiscent of peripheral lymphoid tissue, such as bronchus-or gut-associated lymphoid tissue. The function of this fetal/neonatal intrapancreatic lymphoid tissue (which disappears in later life) is unknown. Various possibilities are suggested such as a yet unknown ubiquitous fetal/neonatal microbial infection, tolerance induction towards islet cell antigens, an endocrine regulatory function of infiltrated lymphoid cells, and a normal ontogenetic process. PMID- 8218829 TI - Antibodies to human cytomegalovirus 65-kilodalton Fc binding protein in rheumatoid arthritis: idiotypic mimicry hypothesis of rheumatoid factor production. AB - We previously reported that rheumatoid factors (RFs) might bear the internal image of Fc gamma-binding proteins (FcBPs) of herpes family viruses, suggesting the possibility that some RFs may be produced as antiidiotypic antibodies to anti viral FcBP antibodies. Since human cytomegalovirus (HCMV) has been implicated in the pathogenesis of RA, we made an attempt to detect antibodies to 65 KD major HCMV FcBP in sera and synovial fluid from patients with RA. Western blotting was performed using HCMV-infected MRC-5 cell lysate as the antigen. Eleven of 23 patients with RA possessed strong serum antibodies to HCMV-65 KD protein, whereas such antibodies were found in only 2 of 23 normal controls. In the synovial fluid, 10 of 19 RA patients showed anti-HCMV 65 KD reactivity. Pepsin-digested IgG retained anti-65 KD reactivity, indicating that false-positive reaction due to the presence of IgG Fc portion and/or RF was unlikely. 65 KD protein was shown to be different from human heat shock proteins (hsps) using monoclonal antibodies against human hsps. Patients' IgG F(ab')2 also reacted with the 65 KD protein of purified HCMV virion itself. These results support the possibility that some RFs could be produced as antiidiotypic antibodies to anti-viral FcBP antibodies. PMID- 8218830 TI - Bacterium-induced autoimmune reactivity. AB - Evidence is growing that autoimmune reactivity results from a combination of endogenous (e.g. MHC type) and environmental factors. Our experimental study focuses on the induction of autoimmune reactivity by microbial factors. Splenic formation and serum levels of anti-erythrocyte antibodies and circulating immune complexes were taken as parameters. It was found that experimental infection of mice with Escherichia coli and Salmonella typhimurium was accompanied by clear signs of autoimmune reactivity, smooth bacteria being almost ten times as potent as rough mutant strains. An attempt was made to correlate the data obtained with live bacteria to their corresponding endotoxins. It was concluded that the induction of more prominent autoimmune reactivity by smooth bacteria must be ascribed to a longer survival time in vivo. Our data support the view that bacterium-derived factors are involved in the etiology (and possibly also the course) of autoimmune diseases. PMID- 8218831 TI - Post-thymectomy organ-specific autoimmunity: enhancement by cyclosporine A and inhibition by IL-2. AB - It has previously been shown that the administration of cyclosporine A to newborn mice results in the development of autoimmunity later in life. It has been proposed that the neonatal administration of cyclosporine A results in altered thymic selection or inhibition of the development of suppressor cells. In the present study, treatment of day 3 thymectomized C3H/HeN mice with cyclosporine A (20 mg/kg/day) for 9 d post surgery increased the prevalence of antigastric autoantibodies. In contrast, the administration of IL-2 (300-600 Units/g/day) for 7 days after thymectomy inhibited the development of antigastric antibodies. We hypothesize that CsA may act by causing transient lymphokine abnormalities in the extrathymic environment during the first few weeks of life which lead to the development of antigastric antibodies. In contrast to the inhibition of development of antigastric antibodies, the administration of a similar course of IL-2 produced only a transient suppression of diabetes in NOD mice. These results and other data suggest that diabetes in NOD mice is probably due to a different immunologic defect. PMID- 8218832 TI - Etiological aspects of insulin-dependent diabetes mellitus: an epidemiological perspective. AB - The mechanism of beta-cell destruction leading to insulin dependent diabetes is probably a cell mediated auto-immune process occurring in genetically susceptible individuals. Since 50-70% of monozygotic twins will not get the disease non genetic risk factors must play an important role in the etiology of the disease. During the past decade population based epidemiological studies have identified several risk determinants for insulin dependent diabetes. Based on these studies a multifactorial hypothesis of causation is proposed. Some risk determinants (maternal child blood group incompatibility, fetal viral infections, early exposure to cow's milk proteins, a high exposure level of nitrosamines) may independently initiate the autoimmune process by causing the initial damage of the beta-cell, leading to antigen release. Other risk determinants may promote an already ongoing autoimmune destructive process through induction of lymphokine release or by causing an increased work load on the beta-cell. Risk factors that may increase the peripheral need for insulin (infectious diseases, cold environment, a high growth rate and stressful life events) may act as promoters of the beta-cell destruction but also disclose the beta-cell impairment and make the disease clinically overt. Possibilities of different risk profiles in different age groups and of synergism between different risk factors are also discussed. PMID- 8218834 TI - Antineutrophil cytoplasmic antibodies and infection. PMID- 8218833 TI - The dysfunction of calcium-ATPase pump in double negative T cells of autoimmune prone mice. AB - Double negative (DN) T cells expanding in peripheral lymphoid tissues in mice bearing lymphoproliferation (lpr) gene are generally unresponsive to mitogens, antigens, and anti-T cell receptor (TCR) or anti-CD3 monoclonal antibodies (mAb). In response to the stimulation with 0.125-5.0 microM ionomycin, control T cells sustained an increase in intracellular free calcium ([Ca2+]i), while DN lpr T cells showed a gradual fall following initial rapid increase in [Ca2+]i. Such gradual fall in [Ca2+]i was overcome by the addition of endoplasmic and sarcoplasmic reticulum Ca(2+)-ATPase inhibitor or high dose (10 microM) of ionomycin. The requirement of high concentration of calcium ionophore for the sustained increase of [Ca2+]i in lpr DN T cells is due to dysfunction of Ca(2+) ATPase pump. PMID- 8218835 TI - The multifactorial nature of MHC-linked susceptibility to insulin-dependent diabetes. AB - Several lines of evidence suggest that major histocompatibility complex (MHC) linked susceptibility to insulin-dependent diabetes mellitus (IDDM) is not restricted to the presence or absence of any single gene product. The existence of population-specific haplotypes associated with IDDM supports the concept that distinct combinations of MHC alleles interact synergistically to induce disease when other environmental and genetic factors are present. MHC-controlled peptide transport and binding to MHC molecules as well as the levels of MHC class I and class II expression in the thymus and pancreatic beta cells may also play significant roles in the outbreak of IDDM. These intrinsic factors shape the T cell receptor (TCR) repertoire during T-cell ontogeny in the thymus and later influence the efficiency of potentially autoreactive T cells in the periphery. Several extrinsic factors, such as viruses or dietary proteins, may be directly involved in the TCR/MHC interaction at the cell surface; furthermore viruses can alter the regulatory mechanisms of peptide/MHC interaction and expression. We propose that these intrinsic and extrinsic factors need not be mutually exclusive and might even be interdependent: a given virus may act deleteriously only when certain autoreactive T cells and combinations of MHC alleles are present in the individual. IDDM would develop if pathogenic T-cells are activated and an appropriate target MHC/peptide is expressed in pancreatic beta cells. Future knowledge of the host-virus relationships influenced by the MHC genes, the function of their encoded proteins and the polymorphic gene structure of well established susceptibility MHC haplotypes will help delineate an overall picture of this issue. PMID- 8218836 TI - Lack of disease recurrence in diabetic BB/Pfd rats after syngeneic islet transplantation. AB - Restimulation of autoreactivity in two different BB rat sublines of the same origin (Ottawa, Canada) was investigated by syngeneic islet transplantation into diabetic animals. Despite identical methods and conditions recurrence of hyperglycaemia was observed in BB/OK rats (Karlsburg, Germany) but not in BB/Pfd rats (Leuven, Belgium). Pancreatic morphology at the time of transplantation revealed significant differences in islet volume density and the degree of insulitis. Additionally, marked differences in the phenotypical composition of cells infiltrating the islets were observed. A loss of autoimmune memory in BB/Pfd rats is discussed as a probable reason for the lack of disease recurrence in those animals. PMID- 8218837 TI - Insulin-dependent diabetes in the NOD mouse model. I. Detection and characterization of autoantibody bound to the surface of pancreatic beta cells prior to development of the insulitis lesion in prediabetic NOD mice. AB - Type I, insulin-dependent diabetes (IDD) results from an autoimmune response against the insulin producing pancreatic beta cells. This autoimmune reaction involves both humoral and cell-mediated factors; nevertheless, the relative role of each remains unresolved. Furthermore, while adoptive transfer experiments have provided evidence for the role of T cells in beta cell destruction, the specific events which initiate leukocyte migration into the islets (insulitis) are unknown. Earlier studies indicated that NOD pancreatic beta cells may bind small amounts of autoantibody. Because of the possible importance of an early humoral response to the initiation of insulitis and subsequent disease, we have investigated a number of aspects of this phenomenon to determine the nature and specificity of the early autoantibodies as well as the time at which autoantibody binds to beta cells. Results of this study demonstrate that NOD/Uf mice are sensitized to islet-cell associated antigens, including GAD, prior to the first appearance of insulitis; that a small percentage of the beta cells of NOD/Uf mice have autoantibody bound to their surface prior to insulitis; that sera collected from preinsulitis NOD/Uf mice contain autoantibodies which will bind to beta cells of both IDD-prone and IDD-resistant mice; and that the autoantibodies which bind pancreatic beta cells are predominantly IgM with lesser amounts of IgG and IgA. These findings suggest that, in the natural course of IDD, insulitis may develop in response to an initial autoantibody-mediated injury of beta cells. PMID- 8218838 TI - T cell tolerance and self/nonself discrimination. AB - T cell tolerance to self antigens is at least partly a reflection of clonal deletion of immature T cells in the thymus. Although it is well accepted that intrathymic tolerance is primarily a reflection of T cell contact with bone marrow (BM)-derived antigen-presented cells (APC), evidence is presented that thymic epithelial cells (TEC) can contribute to tolerance induction. Studies with thymocytes from BM chimeras suggest that selective contact with antigen on TEC induces clonal deletion of a subset of high-affinity T cells; these cells are primarily responsible for in vivo effector functions such as allograft rejection and induction of lethal graft-versus-host disease. Intrathymic contact with TEC fails to delete the typical low-affinity T cells which mediate cytotoxic responses in vitro when cultured with lymphokines. Deletion of these low-affinity T cells appears to require contact with BM-derived APC. Despite the evidence that self tolerance involves clonal deletion in the thymus, it is often stated that backup mechanisms for tolerance induction must exist in the post-thymic environment, but this has yet to be proved. The competing argument is that normal self/nonself discrimination is solely a reflection of intrathymic tolerance: the failure of T cells to react against tissue-specific antigens is not a reflection of post-thymic tolerance but simply that T cells and tissue-specific antigens are kept segregated. PMID- 8218839 TI - A minor group of rheumatoid factors isolated from a patient with rheumatoid arthritis is derived from somatically mutated Vk1 genes further evidence that rheumatoid factors during autoimmune diseases undergo an antigen driven maturation. AB - To better understand the structural basis for rheumatoid factor [RF] activity and the origin of autoantibodies in human autoimmune diseases, we isolated the RF producing B cells from the peripheral blood and from the synovial fluid of a patient suffering from rheumatoid arthritis [RA]. We previously demonstrated that a significant fraction of these RF were derived from three V kappa III genes known to encode most of the monoclonal RF light chain variable regions. To get more insight into the actual repertoire of RF-V kappa genes during RA, we analyzed the nucleotide sequences of RF light chain variable regions of other V kappa families. Using two sets of polymerase chain reactions in order to amplify the cDNA derived from RF producing cells from the same patient KRA, we isolated only three different rearranged V kappa-J kappa complexes: slkv5, slkv7 and bkv42, all derived from V kappa I germ-line genes not previously known to be associated with RF activity; this suggests that the repertoire of VL genes coding for RF during RA is more diverse than the one involved in the generation of paraprotein RF during monoclonal lymphoid proliferations, although there remains a possible bias in favor of the V kappa III family. Moreover, each of these genes is somatically mutated with a pattern suggesting a selective pressure of the antigen. Particularly interesting is the additional proline residue at the V kappa-J kappa junction of bkv42, an unorthodox feature that we found previously in more than 50% of RF V kappa III-J kappa gene complexes. Finally, the homogeneity of some non conservative mutations suggests the existence of a restricted set of pathogenic epitopes driving the production of RF during RA. PMID- 8218840 TI - Oxygen radical production is increased in macrophages from diabetes prone BB rats. AB - Macrophages from autoimmune diabetes prone BB rats were found to produce radical oxygen intermediates (ROI) at an enhanced rate when compared to diabetes resistant BB or normal Wistar rats. The release of ROI was determined by chemiluminescence using in parallel luminol and lucigenin as detector molecules. In diabetes prone BB rats the spontaneous release of ROI was upregulated in macrophages from different compartments, i.e. peritoneum and spleen. Also, maximal output of ROI after activation of macrophages either in vivo by injection of Corynebacterium parvum or in vitro by LPS and IFN was highest for cells from diabetes prone BB rats. This macrophage abnormality was seen in animals prior to recognizable islet inflammation and also was present at the level of macrophages grown in vitro from precursor cells of diabetes prone BB rats. Hypersecretion of oxygen radicals may contribute to Beta cell loss and diabetes development in BB rats. PMID- 8218841 TI - Characterization of distinct islet protein autoantigens associated with type 1 diabetes. PMID- 8218842 TI - Pathogenesis of IDDM: immune regulation and induction of immune tolerance in the NOD mouse. PMID- 8218843 TI - Peripheral tolerance to alloantigen in the adult. PMID- 8218844 TI - Dissection of the pathophysiology of type 1 diabetes by genetic analysis. PMID- 8218845 TI - Pancreatic islet xenotransplantation. PMID- 8218846 TI - Treatment of autoimmune diseases by oral tolerance to autoantigens. PMID- 8218847 TI - Allele-specific DNA-protein interactions associated with the X-box regulatory region of the DQB1*0302 gene. AB - The X box is an essential transcriptional regulatory region for both constitutive and inducible expression of HLA-class II genes, and, while highly conserved among class II genes, both locus- and allele-specific polymorphisms exist. Using gel regardation analysis, we have analyzed the binding of B cell nuclear proteins to the X box regions of the DQB1*0302, *0301, and DRA genes and have identified two distinct X box binding complexes which differ for the diabetes-associated DQB1*0302 allele. PMID- 8218848 TI - Safety and initial clinical efficacy of three dose levels of recombinant activated factor VII (rFVIIa): results of a phase I study. AB - The safety and efficacy of recombinant DNA-produced factor VIIa (rFVIIa) was investigated in 15 haemophilic patients in non-bleeding states and during bleeding episodes (mild to moderate joint bleed). Patients with severe haemophilia A without inhibitors (n = 4), haemophilia A with inhibitors (n = 10), and haemophilia B with inhibitor (n = 1) received one or more doses of rFVIIa during 32 non-bleeding study episodes and 23 bleeding episodes. The study was an open, uncontrolled, dose-escalation (17.5 micrograms/kg, 35 micrograms/kg, 70 micrograms/kg) trial. Physical evaluation, laboratory assessment, and immunology testing were conducted at baseline, monthly for 3 months and every 3 months thereafter. The immediate safety of rFVIIa was assessed by monitoring of D-dimer, fibrinogen, platelet count, antithrombin III, thrombin-antithrombin complex, and alpha 2-antiplasmin 5 min before and at multiple times throughout the following 24 h. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) values were also obtained. Pain, swelling, joint circumference, and range of motion were recorded before administration of the initial dose of rFVIIa in bleeding patients and at 6, 12, and 24 h. Haemostatic response to rFVIIa was observed in patients with severe VIII and IX deficiency with and without inhibitors. Therapy with rFVIIa was judged effective in 19 of the 22 evaluable bleeding episodes at one or more time points. The 35 micrograms/kg and 70 micrograms/kg doses were associated with higher response rates at 6 and 12 h compared to the 17.5 micrograms/kg dose level. A second dose of rFVIIa was administered in 20 of the 22 bleeding episodes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218849 TI - Inter-relationships between haemostatic tests and the effects of some dietary determinants in the Caerphilly cohort of older men. AB - Inter-relationships between fibrinogen, platelets and other haemostatic factors were examined in 1030 men aged 55-99 years. Fasting blood was taken and used for cell counts, platelet counts and platelet parameters, aggregation of platelets to ADP by a whole blood method and a filter test of platelet activation. Plasma fibrinogen, von Willebrand factor, factor VII and plasma viscosity were measured by standard methods. A stressed bleeding time was conducted on the forearm of the arm not used for venepuncture. Variability within the laboratory and short-term intra-subject variation were examined and found to be acceptably small. The effect of age on the tests was modest, except for von Willebrand factor which increased by about 50% of a SD for every 10 years of age. Cholesterol and triglyceride levels had small effects on the platelet tests and a large effect on factor VII. A number of dietary and life-style determinants were examined: smokers had increased levels of fibrinogen, viscosity and white cell count and reduced bleeding times. Alcohol drinkers showed reduced platelet activity and have lower levels of fibrinogen, von Willebrand factor and white cell count. Men who took fish oil capsules had substantially increased bleeding times and lower levels of von Willebrand factor and men who took capsules containing an extract of garlic showed reduced platelet retention in the filter test. PMID- 8218850 TI - A comparative evaluation of ELISAs for D-dimer and related fibrin(ogen) degradation products. AB - This study was designed to (i) characterize two new monoclonal antibodies that react with neoepitopes on fibrin(ogen) fragments D-dimer and D1 and (ii) compare the specificity of these antibodies with that of two commercially available 'D dimer' ELISAs [Dimertest EIA (American Diagnostica, Inc.) and Asserachrom D-Di (Diagnostica Stago)] and also with an ELISA for fibrinolytic fragments containing the E domain complexed with a D (or D-dimer) moiety [Fibrinostika FbDP (Organon Teknika)]. All assays were in a capture (sandwich) ELISA format. Fibrin(ogen) degradation products were isolated in high yield by a novel method involving hydrophobic interaction chromatography. The results disclosed considerable differences in sensitivity and specificity for purified fibrinolytic fragments among all five ELISAs. Although the diagnostic utility of monitoring plasma fibrinolytic fragments is not questioned, our results provide a rational basis for understanding why mAb-based ELISAs for these analytes are not well correlated. If, as our data suggest, the D-dimer ELISAs are not actually measuring the same analytes, then interpretation of studies that determine D dimer concentrations with different methods will be problematic and standardization of D-dimer measurements across assays will be impossible. PMID- 8218851 TI - Plasma kallikrein and thrombin are cleared through unrelated hepatic pathways. AB - Plasma kallikrein (PK) and thrombin (TH), serine proteinases formed from inactive precursors, participate in important body defence mechanisms. The isolated hepatocyte recognizes TH, and the liver clears PK by calcium-independent receptors through mechanisms that are not yet clearly understood. It is known that heparin impairs the binding of TH to isolated liver cells through the inhibition of high affinity receptors. Using an isolated, exsanguinated and perfused rat liver preparation we confirmed that the TH hepatic clearance is calcium-independent and affected by heparin; PK clearance rates both in the presence (t1/2 10 +/- 2 min) or the absence (t1/2 10 +/- 1 min) of heparin were similar; the presence of beta-galactosides does not impair the TH clearance but adversely affects the PK clearance and a large excess of TH does not impair the PK clearance rate (t1/2 6 +/- 1 min). These results indicate that PK and TH are cleared by calcium-independent but otherwise unrelated hepatic pathways and suggest that TH may indeed facilitate the PK clearance by the liver. PMID- 8218852 TI - The clinical expression of hereditary protein C and protein S deficiency: a relation to clinical thrombotic risk factors and to levels of protein C and protein S? AB - We investigated 103 first-degree relatives of 13 unrelated protein C or protein S deficient patients to assess the role of additional thrombotic risk factors and of protein C and protein S levels in the clinical expression of hereditary protein C and protein S deficiency. Fifty-seven relatives were protein C (37) or protein S deficient (20). Thromboembolic events occurred in 30% of protein C deficient and in 35% of protein S deficient persons, compared with 3% and 0% in their normal controls respectively (P < 0.05). In protein C deficient persons, the median thromboembolic event-free survival was 55 years, while in protein S deficiency this interval was 33 years (P = 0.047). In the protein C deficient group 64% of the initial events occurred spontaneously, as did 71% in the protein S deficient group. Recurrent thromboembolic events were more often associated with concomitant risk factors than the initial events: 64% and 50% in persons with protein C or protein S deficiency respectively. These findings suggest a substantial role for these risk factors in triggering thromboembolic events in deficient persons. Protein C antigen and protein S antigen levels were similar in symptomatic and asymptomatic deficient persons. Total, but not free, protein S antigen levels were significantly higher in symptomatic protein C deficient persons, as were protein C antigen and activity levels in symptomatic protein S deficient ones. The clinical implication of this finding is not yet clear. PMID- 8218853 TI - Rebound increase of PAI-1 following local intra-arterial rt-PA infusion, a possible cause of reocclusion. AB - We studied systemic changes in the plasminogen activating system induced by local intra-arterial infusion of recombinant t-PA (rt-PA) in ten patients with arterial occlusion. The arterial infusion of rt-PA resulted in an immediate increase of t PA activity and antigen in venous plasma. Concomitantly the plasma was depleted of PAI-1 activity with a moderate decrease of PAI-1 antigen, presumably due to immediate complexing of rt-PA by PAI-1 and gradual elimination of the rt-PA/PAI-1 complex from the circulation. Activation of plasminogen in the circulation was reflected by the occurrence of fibrinogen/fibrin degradation products. This rapid systemic activation of the fibrinolytic system at local intra-arterial administration of rt-PA might be due to the opening of small collaterals or backward flow through open arteries, allowing rt-PA to enter the general circulation. The disappearance of detectable PAI-1 activity during rt-PA infusion was followed by a rebound effect with a significant increase of PAI-1 antigen. As this increase may have contributed to the reocclusion which occurred in four patients, it might be advisable to replace heparin by rt-PA at a lower dosage in the immediate phase following rt-PA infusion. PMID- 8218854 TI - Anticoagulant potential of synthetic and recombinant inhibitors of factor Xa and thrombin in vitro. AB - The anticoagulant effects of thrombin inhibitors in vitro and ex vivo are well characterized. Inhibitors of factor Xa might also be effective as anticoagulants. We studied several synthetic, low-molecular-weight inhibitors with varying affinity to thrombin and factor Xa using three in vitro clot-based assays representative of the effects of thrombin added or generated via the intrinsic or extrinsic coagulation pathways. The recombinant selective thrombin and factor Xa inhibitors, hirudin and antistasin, were studied for comparison. The thrombin time assay is a measure of the antithrombin potential of a given inhibitor, while the activated partial thromboplastin time is influenced by inhibition of thrombin and/or of factor Xa in a similar manner. The prothrombin time assay was more sensitive to inhibition of factor Xa, as evidenced by the potent and selective inhibitor antistasin as well as for less potent and less selective synthetic inhibitors of factor Xa. Direct synthetic or recombinant inhibitors of factor Xa with Ki values in the submicromolar range were potent anticoagulants, approaching or exceeding the potency of hirudin in prolonging the prothrombin time and the activated partial thromboplastin time in vitro. PMID- 8218855 TI - Increased plasma level of interleukin-6 in disseminated intravascular coagulation. AB - Plasma interleukin-6 (IL-6) was higher in patients with disseminated intravascular coagulation (DIC) than in those without DIC. Levels of IL-1 beta and TNF alpha were also significantly higher in patients with DIC. Plasma IL-6 was highest in patients with underlying sepsis and was also high in those with advanced solid cancer. Levels were high in some patients with acute promyelocytic leukaemia and were significantly higher in patients with organ failure than in those without this complication. Plasma IL-6 was higher in DIC patients showing a poor response to therapy than in those with a good response. Incubation with IL-6 caused significant increases in tissue factor activity in mononuclear cells and release of plasminogen activator-1 antigen from human umbilical vein endothelial cells. As increases in IL-6 might give rise to hypercoagulable and hypofibrinolytic states, this may be a cause of DIC and be related to prognosis and organ failure. PMID- 8218856 TI - Stimulation of tissue type plasminogen activator by leukaemic cell homogenates. AB - In patients with disseminated intravascular coagulation (DIC), hyperfibrinolysis was observed in patients with leukaemia, but hypofibrinolysis was seen in those with sepsis. Although the plasma tissue plasminogen activator (t-PA) level was higher in patients with DIC than in those without DIC, there was no significant difference in t-PA level between the patients with leukaemia and sepsis. Hyperfibrinolysis might not be caused by t-PA derived from leukaemic cells, although the PA antigen level in leukaemic cell homogenates was significantly higher in patients with DIC than in those without DIC. The activation of t-PA by leukaemic cell homogenates in the absence of bromocyan fibrinogen fragments suggested that leukaemic cell homogenates had t-PA stimulator activity. The t-PA stimulator activity was high in both acute myeloblastic leukaemia (AML) and acute lymphoblastic leukaemia (ALL), especially in DIC, but this activity was not detected in chronic myelocytic leukaemia (CML) or normal cells. Since fibrinogen and soluble fibrin monomer complex levels in leukaemic cells were also high in patients with DIC, fibrinogen degradation products might be the major t-PA stimulator in leukaemic cells. This might be one of the causes of hyperfibrinolysis in leukaemia. PMID- 8218857 TI - Evaluation of solvent/detergent treated plasma in the management of patients with hereditary and acquired coagulation disorders. AB - Haemostatic efficacy and pharmacokinetic analysis of solvent/detergent (S/D) treated, virus inactivated plasma (Octaplas, Germany) was evaluated in eight patients with hereditary factor VII, X and XI deficiency and in three patients with acquired coagulation disorders due to liver disease. The patients received the S/D plasma for treatment of haemarthrosis, menorrhagia or before surgical procedures. In all the patients the S/D plasma was sufficient to prevent or stop bleeding. Side effects included urticaria (one patient) and moderate anaphylactoid reaction (one patient). No evidence of plasma-born viral infections was observed up to 12 months after the treatment (95% confidence limits 0-22%). Calculated mean half-life of coagulation factors VII, X and XI was 4.36 h, 49.21 h and 44.5 h, respectively, similar to that observed with fresh-frozen plasma. Because of retained coagulation factor integrity and improved viral safety, S/D plasma could be considered a superior alternative to standard fresh-frozen plasma. PMID- 8218858 TI - Protein C activation by an activator purified from the venom of Agkistrodon halys halys. AB - The protein C activator from Agkistrodon halys halys venom was purified 533-fold by ion-exchange chromatography on QAE-Sephadex A-50, affinity chromatography on aprotinin-Sepharose and Mono-Q fast protein liquid chromatography. The purified enzyme is a single chain protein with an apparent molecular weight of 36,000 that activates protein C by proteolytic removal of a small fragment from the heavy chain. The protein C activator exhibited a high amidolytic activity towards the tripeptide substrates D-Pro-Phe-Arg-pNA (S2302) and D-Phe-(pipecolyl)-Arg-pNA (S2238). The activity of the activator was not affected by thiolprotease or metalloprotease inhibitors. The activator was inhibited, however, by benzamidine, Phe-Pro-Arg chloromethyl ketone, p-nitrophenyl p-guanidinobenzoate and soy bean trypsin inhibitor, which classifies the enzyme as a serine protease. The purified protease was capable of activating both human and bovine protein C. Activation of human protein C only occurred at an appreciable rate in a calcium-free reaction medium at low ionic strength. Ca2+ ions inhibited the activation of human protein C with an apparent Ki of 0.8 mM. Addition of NaCl to the reaction medium also strongly inhibited human protein C activation (50% inhibition at 20 mM NaCl). Kinetic analysis of human protein C activation by the venom activator (in a calcium-free medium) revealed an apparent Km for protein C of 0.52 microM and a kcat of 0.17 s-1 at I = 0.05 (kcat/Km = 3.3 x 10(5) M-1 s-1). At I = 0.15 rates of human protein C activation became linear with protein C indicating a strong increase in Km with increasing ionic strength. Activation of bovine protein C was hardly affected by variation of Ca2+ and NaCl concentrations in the reaction medium. The apparent Kis for calcium ion and NaCl inhibition of bovine protein C activation were > 10 mM and 220 mM, respectively. At I = 0.1 and in the absence of Ca2+ ions bovine protein C was activated with a Km of 0.056 microM and a kcat of 0.24 s-1 (kcat/Km = 4.3 x 10(6) M-1 s-1). Our data are indicative for a rather large conformational and/or structural difference between human and bovine protein C at physiological ionic strength. PMID- 8218859 TI - Mechanisms of thromboembolism at arterial plaques. AB - Thrombus formation at a ruptured arterial plaque forming a stenotic luminal outgrowth may trigger acute vascular occlusion. The pathobiology of the complex mechanisms and their interrelationships during this event is not fully understood. However, it is generally believed that components of the subendothelial plaque and the disturbed blood flow conditions caused by the stenosis are of pivotal importance for the thrombus formation. The shape and the severity of the occluding stenosis have profound impacts on the physical aspects of the blood flow. The wall shear rate at the apex may reach extremely high values (> 40,000 s-1). Zones of recirculation proximal and distal to the stenosis as well as turbulent blood flow further downstream from the lesion may occur. The significance of these rheological factors for the mural thrombus formation at various locations at the stenosis is not well established. The extracellular matrix and the cellular components of the subendothelial plaque exposed to the blood stream following plaque rupture are potent inducers of thrombus formation. Matrix components such as collagen fibrils, fibronectin and von Willebrand factor interact specifically with platelet membrane glycoprotein receptors, Ia-IIa, Ib IX, and IIB-IIa, enabling platelet-subendothelium adhesion, particularly at high wall shear rates. The coagulation cascade is concomitantly activated by the binding of FVII from plasma to tissue factor expressed on the membranes of macrophages and smooth muscle cells. Thrombin, which is subsequently generated at the rupture, enhances the platelet recruitment, and thus the thrombus growth. The thrombin formation simultaneously enhances the deposition of fibrin in and around the platelet masses. Further augmentation of these processes is mediated by the formation of prothrombinase complexes on the phospholipid-rich surfaces of the activated platelets, which increases the local concentration of thrombin at the evolving thrombus. Thrombus fragmentation may represent a serious event, since these fragments may embolize and occlude smaller vessels, producing ischaemia. It is apparent that acute arterial thrombotic occlusion triggered by a ruptured stenotic plaque involves both physical and chemical mechanisms. The inter relationship and the significance of these complex mechanisms are not well understood. Efficient modalities for therapeutic intervention in thromboembolism at such lesions may not be available before the physical and chemical events are better identified and characterized. PMID- 8218860 TI - Monitoring of haemostatic parameters in five cases of Amanita phalloides poisoning. AB - The effects of Amanita phalloides poisoning on haemostatic parameters were determined in five members of two families with particular attention to coagulation inhibitors. According to the prothrombin time and factor V level, one patient had severe poisoning, one moderate and the other three had only mild toxicity. The decrease of inhibitors (antithrombin III, proteins C and protein S) was not followed by coagulation activation as assessed by the moderate increase in D-dimers and the absence of a clinically significant coagulopathy. Anti thrombin III showed little decrease, except in the more severely affected case and protein C paralleled the decrease in factor VII, but to a lesser extent. The decrease in coagulation factors and inhibitors could not be explained by their half-lives alone. Factor V was a better indicator of the recovery of liver synthesis function than other factors. Our observations indicate that monitoring coagulation inhibitors in Amanita poisoning is not more informative than prothrombin time and coagulation factor V, both usually recognized as early prognostic markers of fulminant hepatic failure. PMID- 8218861 TI - A novel point mutation (Val 297-->Met) in the serine proteinase domain of protein C in a patient with both venous and arterial thromboembolic disease. AB - A novel heterozygous GTG-->ATG (Val 297-->Met) substitution was detected in an individual with probable inherited protein C deficiency and both venous and arterial thrombotic disease. The lesion occurs in a highly conserved residue within the serine protease domain. In a molecular model of protein C, Met 297 makes unfavourable interactions with neighbouring residues suggesting that the mutant protein is unable to adopt a stable/functional conformation. PMID- 8218862 TI - Enzymatic elimination of heparin from plasma for activated partial thromboplastin time and prothrombin time testing. AB - The prolongation of the APTT and PT by heparin can be neutralized by treating the plasma with heparinase or with certain anion-exchangers. The purpose of the present study was to assess the effectiveness of a new commercial heparinase reagent. Heparinase (Hepzyme) for the removal of heparin from plasma was compared with ECTEOLA-cellulose treatment. In ex vivo heparin samples, shorter APTT values were obtained with heparinase than with ECTEOLA-cellulose, suggesting that the former treatment is more effective for the removal of heparin from plasma. Heparinase (Hepzyme) treatment may be used to improve INR assessment in patients treated with heparin and oral anticoagulants concomitantly. PMID- 8218864 TI - Abnormal fibrinolytic activity in African women taking oral contraceptives. PMID- 8218863 TI - The relative frequency of inherited inhibitor deficiency among 93 young patients with thrombophilia in Algeria. PMID- 8218865 TI - [Lectures of the 27th annual meeting of the German, Austrian, and Swiss Societies for Medical and Biomedical Engineering. Graz, 16-18 September 1993]. PMID- 8218867 TI - [Assessment of whole cell deformability of individual erythrocytes with a capillary rigidometer--possibilities for standardization and modification]. AB - Human erythrocyte deformability is determined by cell geometry and volume, membrane elasticity and cytoplasmic viscosity. The deformability of red blood cells and their distribution among the total cell population, can be studied with the Capillary Rigidometer. This device is based on the kinetic measurement of red blood cell deformability, which has been developed, by modifying the micropipette aspiration technique. In order to investigate the validity of the method and the measuring parameters, a number of determining factors (heat treatment, osmolarity changed cells) influencing the deformability were studied, and the sensitivity of the defined parameters for changes in deformability discussed. The results are examined in connection with different flow rates in the micropipette and show that the parameters are influenced by the flow conditions, so that they have to be related to these conditions. Initial studies using microspheres aimed at standardising the method are described. PMID- 8218866 TI - [Importance of newly defined epiphyseal version in diagnosis and therapy of epiphysiolysis capitis femoris (additional data to epiphyseal dislocation and epiphyseal torsion)]. AB - The displacement of the femoral epiphysis in epiphyseolysis capitis femoris is usually determined by measuring both the epiphysis-diaphysis angle (ED angle) in the plane of the dislocation and the epiphysis-torsion angle (ET angle) in the torsional plane. In this paper we define an epiphyseal version angle (EV angle) in the sagittal plane of the femur, calculate it trigonometrically and show it in diagrams and tables. The clinical application of the EV angle indicates that in cases of displacement with an ED angle of less than 135 degrees, absolute displacement is better shown than with the ET angle. Additionally, the EV angle improves our comprehension of the 3-D displacement due to the fact that, in the "Lauenstein" x-ray, the femur is increasingly projected more in a sagittal plane with increasing abduction. The essential correction using the Imhauser-osteotomy is also done in the sagittal plane. The ability of the orthopaedic surgeon to visualize the situation in three dimensions is also improved by this additional standard plane. PMID- 8218868 TI - [Utilization of CT image data for preparation of thermoradiotherapy]. AB - Medical imaging procedures are providing qualitative and, increasingly, quantitative diagnostic information on the morphology and function of the human organism. As possibilities for communication and data processing continue to grow, they are also being applied in the field of therapy. Taking combined local radiotherapy and thermotherapy for the treatment of uterine carcinoma as an example, this paper describes the integration of the biological-pathological situation into the modelling of isothermal profiles using the patient's image data. PMID- 8218869 TI - [Possibilities for recognizing and suppressing artifacts in EMG signals]. AB - Two methods are introduced to suppress artifacts in the EMG signal, as can occur with EMG detection. These methods are based upon an adaptive threshold, which depends on the muscle activity measured just before. Even small artifacts are identified and suppressed in a small EMG, so if they are not too long in duration they do not noticeably falsify the muscle activity detection. These methods are quite effective, simple and thus easily realizable. PMID- 8218870 TI - Pharmacokinetic model for the absorption of subcutaneously injected soluble insulin and monomeric insulin analogues. AB - A subcutaneous insulin absorption model is presented for parameter estimation from the time course of plasma insulin. Modifications of a published model were made for the absorption of soluble insulin and monomeric insulin analogues in the range of therapeutic concentrations and volumes. The modified diffusion dissociation model with distributed parameters was approximated by a multiple compartment model. Subcutaneous absorption of soluble insulin and monomeric insulin analogues with various volumes, concentrations, and injection depths was simulated. The model for soluble insulin exhibits volume, concentration, and injection depth dependent absorption, as experimentally observed. It was found that binding of soluble insulin in the subcutaneous tissue is negligible for U-40 and U-100 strengths. The absorption of identical doses (10 U) of soluble U-40 insulin was markedly faster (T-50% = 159.4 min) than the absorption of U-100 (T 50% = 196.2 min). According to the simulation results, the absorption rate of monomeric analogues is not dependent on concentration. No significant chances of the absorption rate could also be observed by varying volume and injection depth of the monomeric analogues. PMID- 8218871 TI - Cancer of the large bowel in women in relation to alcohol consumption: a case control study in Wisconsin (United States). AB - Age-specific consumption of beer, wine, and liquor was ascertained by telephone interview from 779 women in Wisconsin (United States) with newly reported diagnosis of carcinoma of the colon and rectum. Population controls (n = 2,315) interviewed for this case-control study were randomly selected from Wisconsin driver's license files and Health Care Financing Administration files. Overall, there was a modest indication that high levels of alcohol consumption (11 or more drinks per week) were associated with increased risk of large bowel cancer (adjusted odds ratio [OR] = 1.47, 95 percent confidence interval [CI] = 1.0 2.22). In site-specific analyses, only rectal cancer demonstrated a significant linear trend (P = 0.01) with increasing consumption. Significant beverage specific effects were observed for liquor and colon cancer: the adjusted ORs for 1-2, 3-5, and 6+ drinks per week were 1.12, 1.68, 1.51, respectively (P trend = 0.01). Beer was associated significantly with rectal cancer: the adjusted ORs for 1-2, 3-5, 6-10, and 11+ drinks per week were 1.25, 1.25, 1.58, 2.42, respectively (P trend = 0.02). Wine consumption was associated inversely with these cancers. These relationships appeared to be consistent for recent, past, and total lifetime consumption, and were not attributable to differences in dietary habits. PMID- 8218872 TI - Melanoma: linked temporal and latitude changes in the United States. AB - The rise in the incidence and mortality from melanoma of the skin is slowing down in younger age groups in the United States. In many White populations, including that of the US, melanoma incidence and mortality rates increase according to proximity of residence to the Equator. Variations with age in this gradient do not seem to have been examined. We examined how the influence of latitude on melanoma rates varied with age. Estimates of age-specific trends by time and by latitude for natural logarithm (Ln) melanoma incidence-rates from the Surveillance, Epidemiology and End Results (SEER) programs, and Ln melanoma mortality rates from the US Vital Statistics were derived from fitted regression equations. Unexpectedly, a decline from old age to youth in the influence of latitude was found for both incidence and mortality from melanoma of the skin in males, and for mortality in females. Further, these changes in the relationship to latitude with age correlated with the changes in time trends with age. The link with exposure suggests that the time trends in melanoma are driven by variations in damage to melanocytes in early life that increases sensitivity to sunlight. This has implications for the general understanding of melanoma etiology and for health education. PMID- 8218873 TI - Incidence of cancer among male waiters and cooks: two Norwegian cohorts. AB - Previous occupational survey studies have identified 'waiter' and 'cook' as possible high risk occupations for cancer. However, few cohort studies have been performed among persons in the restaurant business, and we therefore have analyzed cancer incidence in two cohorts of Norwegian waiters and cooks. The cohorts consisted of skilled male workers, 1,463 waiters and 2,582 cooks, who received their craft certificate between 1958 and 1983. The cohorts were followed from 1959 through 1991. The standardized incidence ratio (SIR) for all causes of cancer was 1.4 (95 percent confidence interval [CI] = 1.2-1.7] for waiters, and 1.1 (CI = 0.9-1.4) for cooks. Cancers of the tongue, mouth, pharynx, larynx, esophagus, and liver were grouped together as alcohol-associated cancers. SIR for these cancers combined was 5.1 (CI = 3.4-7.4) for waiters and 4.2 (CI = 2.2-7.2) for cooks. For lung cancer, SIR was 2.0 (CI = 1.3-2.9) for waiters and 0.7 (CI = 0.2-1.7) for cooks. For alcohol-associated cancers, the analysis carried out according to number of years since first employment showed a larger number of cases than expected for both occupations in all time-periods. The excess of lung cancer cases among waiters appeared after 30 years or more of employment. The study shows that waiters and cooks are at high risk of cancers associated with alcohol consumption, and that waiters, in addition, show high rates for lung cancer. The hypothesis of an occupational lung-cancer risk in cooks was not supported by this study. PMID- 8218874 TI - Mortality among workers at a nuclear power plant in the United States. AB - A second follow-up of 9,000 workers at the Calvert Cliffs Nuclear Power Plant (MD, USA) identified 346 deaths in the years 1969-88, 101 of which were attributed to malignant neoplasms. The original study had the primary purpose of assessing the feasibility of studies of workers based upon individual plant and Nuclear Regulatory Commission records. The average, cumulative, occupational dose through 1984 was low, only 21 mSv, but ranged up to 470 mSv, with 12 percent of the workers receiving more than 50 mSv. Mortality from most causes of death was low and there was a deficit of deaths from diseases of the circulatory system. Ionizing radiation exposures were not related to the probability of death from neoplasms generally or from any specific form of cancer. There were only two deaths from leukemia, whereas four were expected at population death rates. Larger numbers of workers, followed for longer periods of time, are needed to determine the mortality risk to workers in the nuclear power industry. The difficulties in obtaining dose information for transient workers were so great, and so time consuming, as to make questionable the practicability of studying the workers at a large number of power plants in this way. PMID- 8218875 TI - A case-control study of thyroid cancer in women under age 55 in Shanghai (People's Republic of China). AB - A population-based interview study of 207 case-control pairs investigated reproductive, dietary, and other factors thought likely to increase thyroid cancer risk among women of reproductive age in Shanghai. Of particular interest were factors that might help explain the striking female over male excess in this age group. Risk was strongly associated with prior goiter or benign nodules (odds ratio [OR] = 7.0, 95 percent confidence interval [CI] = 2.5-27.5) and miscarriage as outcome of first pregnancy (OR = 9.9, CI = 2.0-48.4). Weaker associations were seen for women who were ever-pregnant (OR = 2.1, CI = 1.1-4.2), ever had an induced abortion (OR = 1.6, CI = 0.9-2.9), and ever used oral contraceptives (OR = 1.7, CI = 1.0-3.1). Compared with controls, cases gained significantly more weight from menarche to highest nonpregnant weight (P trend < 0.01). Overall, cases ate more fish and shellfish, but there was no trend with level of consumption. More cases had a parent, sibling, or child with thyroid disease (OR = 5.2, CI = 2.5-12.1). Our findings relating to goiter and benign nodules and various reproductive factors support earlier studies. Consumption of seafood was difficult to evaluate; more detailed dietary data are needed to assess iodine intake. PMID- 8218876 TI - Recall and selection bias in reporting past alcohol consumption among breast cancer cases. AB - Recall and selection bias are well-recognized potential problems in case-control studies of alcohol and cancer, but few analyses have attempted to assess the direction and the magnitude of these potential biases. We thus examined alcohol consumption in relation to risk of breast cancer using dietary questionnaires administered both before and after the diagnosis of breast cancer in the Nurses' Health Study (United States). Among cohort members who completed a dietary questionnaire in 1986 and who were free of cancer, 616 were diagnosed with breast cancer during follow-up to December 1989. These cases and 1,277 controls (a random sample of cohort members who did not develop cancer up to 1990) then were sent another questionnaire inquiring about their diet in 1985. Four hundred and ninety-four cases (80.2 percent) and 999 controls (78.2 percent) responded to the second questionnaire. The analysis based on the prospective (1986) questionnaire demonstrated an elevated risk of breast cancer among women who drank 30 or more g of alcohol daily (about two drinks) relative to nondrinkers (odds ratio [OR] = 1.55, 95 percent confidence interval [CI] = 1.01-2.39). The analysis based on the retrospective questionnaire also indicated a similar but slightly attenuated elevation of risk of breast cancer among women who drank at least 30 g daily (OR = 1.42, CI = 0.85-2.40). In these data, bias due to selection and recall had only minor effects on reported intake of alcohol consumption. PMID- 8218877 TI - Occupational risk factors for lung cancer among nonsmoking women: a case-control study in Missouri (United States). AB - Occupationally related risk of lung cancer among women and among nonsmokers has not been widely studied. A recently conducted population-based, case-control study in Missouri (United States) provided the opportunity to evaluate risk of lung cancer associated with several occupational factors. Incident cases (n = 429) were identified through the Missouri Cancer Registry for the period 1986 through 1991, and included 294 lifetime nonsmokers and 135 ex-smokers who had stopped at least 15 years prior to diagnosis or had smoked for less than one pack year. Controls (n = 1,021) were selected through driver's license and Medicare files. Risk was elevated among women exposed to asbestos (ever: odds ratio [OR] = 3.5, 95 percent confidence interval [CI] = 1.2-10.0; > 9 yrs: OR = 4.6, CI = 1.1 19.2) and pesticides (ever: OR = 2.4, CI = 1.1-5.6; > 17.5 yrs: OR = 2.4, CI = 0.8-7.0). Risk also was elevated among dry cleaning workers (ever: OR = 1.8, CI = 1.1-3.0; > 1.125 yrs: OR = 2.9, CI = 1.5-5.4). Occupational risks for lung cancer among women merit further study. PMID- 8218878 TI - Family history of cancer and seizures in young children with brain tumors: a report from the Childrens Cancer Group (United States and Canada). AB - The occurrence of cancer and neurological disorders in first- and second-degree relatives of children in the United States and Canada diagnosed with brain tumor before age six was investigated. A pair-matched case-control study with 155 astrocytoma and 166 primitive neuroectodermal tumor (PNET) cases was performed. Cases were identified through the Childrens Cancer Group. Controls were selected by random-digit dialing and matched to cases on age, race, and telephone area code and exchange. Childhood cancers were more common in PNET relatives compared with the general population (standardized incidence ratio [SIR] = 2.5, 95 percent confidence interval [CI] 1.1-4.8, P = 0.02) and with control relatives (odds ratio [OR] = 3.0, CI = 0.5-30, P = 0.29). For astrocytoma, nonsignificant excesses of brain tumor, leukemia/lymphoma, and childhood cancer occurred among case relatives compared with control relatives, but not compared with the general population. Astrocytoma cases were significantly more likely than controls to have a relative with seizures (OR = 2.5, CI = 1.2-4.9, P = 0.009), especially childhood seizures (OR = 3.4, CI = 1.2-12, P = 0.02), epilepsy (OR = 3.0, CI = 0.9-13, P = 0.08), and febrile convulsions (OR = 4.5, CI = 0.9-43, P = 0.07). A family history of stroke was not a risk factor for either type of brain tumor. These results suggest that some childhood brain tumors may result from a genetic susceptibility and that some risk factors may affect childhood astrocytoma and PNET differently. PMID- 8218879 TI - Occupational exposure to electromagnetic fields in relation to leukemia and brain tumors: a case-control study in Sweden. AB - Occupational exposure to low-frequency electromagnetic fields (EMF) was studied in 250 leukemia patients and 261 brain-tumor cases, diagnosed in 1983-87 and compared with a control group of 1,121 randomly selected men, from the mid-region of Sweden, 1983-87. We based the exposure assessment on measurements from 1,015 different workplaces. On the basis of the job held longest during the 10-year period before diagnosis, we found an association between the average, daily, mean level of EMF and chronic lymphocytic leukemia (CLL). The risk increased with increasing level of exposure. The odds ratios (OR) and the 95 percent confidence interval (CI) for three consecutive levels of exposure were: 1.1 (CI = 0.5-2.3); 2.2 (CI = 1.1-4.3); 3.0 (CI = 1.6-5.8), respectively. No association was observed for acute myeloid leukemia (OR = 1.0, CI = 0.5-1.8; OR = 0.8, CI = 0.4-1.6; OR = 1.0, CI = 0.6-1.9). For brain tumors, the corresponding risk estimates were 1.0 (CI = 0.7-1.6); 1.5 (CI = 1.0-2.2); 1.4 (CI = 0.9-2.1). Different EMF indices were tested. Tasks with frequent or large variations between high and low field densities (high standard deviation) were more common among CLL subjects. For brain tumors, a prolonged high level (high median values) showed the strongest association. Confounding by place of residence, smoking, benzene, ionizing radiation, pesticides, and solvents was evaluated, and these factors did not seem to have a decisive influence on the associations. We also analyzed other potential sources of bias. For CLL, there were indications of an excess number of low-exposure subjects among non-responders, which, to some extent, may have enhanced but not caused the risk estimates obtained. Our conclusion is that the study supports the hypothesis that occupational EMF exposure is a hazard in the development of certain cancers. PMID- 8218881 TI - What is progress against cancer? PMID- 8218880 TI - A cohort study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States). AB - Risk factors for pancreatic cancer were evaluated in a cohort study of 17,633 White men in the United States who responded to a mailed questionnaire in 1966 and were followed-up through 1986 for mortality. Cigarette smoking and alcohol consumption were found to be important risk factors for pancreatic cancer. Risks increased significantly with number of cigarettes smoked, reaching fourfold for smokers of 25 or more cigarettes per day relative to nonsmokers. Alcohol intake also was related significantly to risk, with consumers of 10 or more drinks per month having three times the risk of nondrinkers, but dose-response trends among drinkers were not smooth. Coffee consumption was unrelated to risk. Dietary analyses revealed a rising rate of pancreatic cancer mortality with increasing consumption of meat after adjustment for other risk factors. Men in the highest quartile of meat intake had about three times the risk of those in the lowest quartile. No consistent association, however, was observed for consumption of fruits, vegetables, or grains. This study confirms cigarette smoking as an important risk factor for pancreatic cancer, and provides evidence that elevated intake of alcohol and meat may increase the risk of this fatal malignancy. PMID- 8218882 TI - Previous cancer and radiotherapy as risk factors for lung cancer in lifetime nonsmokers. AB - A history of previous primary cancer and of radiotherapy were investigated as risk factors for lung cancer in lifetime nonsmokers in a hospital-based case control study. By design, subjects with a previous tobacco-related primary (of the lung, larynx, oropharynx, esophagus, kidney, bladder, or pancreas) were excluded. Information was available on 30 male and 47 female lung cancer cases and 87 male and 132 female controls, all lifetime nonsmokers, interviewed in hospitals in four United States cities between 1985 and 1990. In males, neither a history of a previous primary nor a history of radiotherapy was associated significantly with lung cancer; however, the numbers of exposed cases were small. In females, after adjustment for age, education, hospital, lifetime environmental tobacco-smoke exposure, and body mass index, both a history of a reproductive primary and a history of radiotherapy were associated significantly with lung cancer (odds ratio [OR] = 4.9, 95 percent confidence interval [CI] = 1.4-17.7, and OR = 4.4, CI = 1.3-15.1, respectively). Due to a high correlation between a history of a reproductive primary and a history of radiotherapy in the cases, it was not possible to estimate the effect of one exposure independent of the other. These results are consistent with the possibility that endocrine factors may play a role in some lung cancers in women. PMID- 8218883 TI - Ca2+i versus [Ca2+]i. PMID- 8218884 TI - Why is the purple membrane a two-dimensional crystal? PMID- 8218885 TI - Importance of islet cell synchrony for the beta-cell glucose response. PMID- 8218886 TI - Dynamic microtubule simulation, seams and all. PMID- 8218887 TI - Selective electrofusion of conjugated cells in flow. AB - Using a modified flow cytometer we have induced electrofusion of K562 and L1210 cells in flow. The two cell types are stained with two different fluorescent membrane probes, DiO and DiI, to facilitate optical recognition, and then coupled through an avidin-biotin bridge. In the flow cytometer, the hydrodynamically focused cells and cell pairs are first optically analyzed in a normal flow channel and then forced to flow through a Coulter orifice. If the optical analysis indicates that a cell pair is present, an electric pulse is applied across the orifice to induce fusion. The pulsed cell pairs were subsequently analyzed using normal and confocal microscopy to evaluate fusion induction. It appears that fusion can be induced in about 10% of pulsed cell pairs when one electric pulse with a duration of 10-15 microseconds and an effective electric field strength of 4-8 10(5) V/m is used. PMID- 8218888 TI - Direct visualization of polypeptide shell of ferritin molecule by atomic force microscopy. AB - The polypeptide shell of the ferritin molecule has been imaged in water by atomic force microscopy (AFM). The central dip and the quaternary structure could be observed on the surface of the ferritin molecule anchored inhomogeneously in two dimensions. These structures observed in the AFM images are quite similar to the electron density map near the top of the apoferritin viewed down from a 4-fold axis structure reported previously (S. H. Banyard, D. K. Stammers, and P. M. Harrison, 1978. Nature (Lond.). 271:282-284). It has been achieved by introducing a "self-screening effect" of the surface charges of the AFM sample (S. Ohnishi, M. Hara, T. Furuno, and H. Sasabe. 1992. Biophys. J. 63:1425-1431) and the specially sharpened stylus of AFM cantilever. PMID- 8218889 TI - Dynamic instability of microtubules: Monte Carlo simulation and application to different types of microtubule lattice. AB - Dynamic instability is the term used to describe the transition of an individual microtubule, apparently at random, between extended periods of slow growth and brief periods of rapid shortening. The typical sawtooth growth and shortening transition behavior has been successfully simulated numerically for the 13 protofilament microtubule A-lattice by a lateral cap model (Bayley, P. M., M. J. Schilstra, and S. R. Martin. 1990. J. Cell Sci. 95:33-48). This kinetic model is now extended systematically to other related lattice geometries, namely the 13 protofilament B-lattice and the 14-protofilament A-lattice, which contain structural "seams". The treatment requires the assignment of the free energies of specific protein-protein interactions in terms of the basic microtubule lattice. It is seen that dynamic instability is not restricted to the helically symmetric 13-protofilament A-lattice but is potentially a feature of all A- and B-lattices, irrespective of protofilament number. The advantages of this general energetic approach are that it allows a consistent treatment to be made for both ends of any microtubule lattice. Important features are the predominance of longitudinal interactions between tubulin molecules within the same protofilament and the implication of a relatively favorable interaction of tubulin-GDP with the growing microtubule end. For the three lattices specifically considered, the treatment predicts the dependence of the transition behavior upon tubulin concentration as a cooperative process, in good agreement with recent experimental observations. The model rationalizes the dynamic properties in terms of a metastable microtubule lattice of tubulin-GDP, stabilized by the kinetic process of tubulin GTP addition. It provides a quantitative basis for the consideration of in vitro microtubule behaviour under both steady-state and non-steady-state conditions, for comparison with experimental data on the dilution-induced disassembly of microtubules. Similarly, the effects of small tubulin-binding molecules such as GDP and nonhydrolyzable GTP analogues are readily treated. An extension of the model allows a detailed quantitative examination of possible modes of substoichiometric action of a number of antimitotic drugs relevant to cancer chemotherapy. PMID- 8218890 TI - Diffusion of extracellular K+ can synchronize bursting oscillations in a model islet of Langerhans. AB - Electrical bursting oscillations of mammalian pancreatic beta-cells are synchronous among cells within an islet. While electrical coupling among cells via gap junctions has been demonstrated, its extent and topology are unclear. The beta-cells also share an extracellular compartment in which oscillations of K+ concentration have been measured (Perez-Armendariz and Atwater, 1985). These oscillations (1-2 mM) are synchronous with the burst pattern, and apparently are caused by the oscillating voltage-dependent membrane currents: Extracellular K+ concentration (Ke) rises during the depolarized active (spiking) phase and falls during the hyperpolarized silent phase. Because raising Ke depolarizes the cell membrane by increasing the potassium reversal potential (VK), any cell in the active phase should recruit nonspiking cells into the active phase. The opposite is predicted for the silent phase. This positive feedback system might couple the cells' electrical activity and synchronize bursting. We have explored this possibility using a theoretical model for bursting of beta-cells (Sherman et al., 1988) and K+ diffusion in the extracellular space of an islet. Computer simulations demonstrate that the bursts synchronize very quickly (within one burst) without gap junctional coupling among the cells. The shape and amplitude of computed Ke oscillations resemble those seen in experiments for certain parameter ranges. The model cells synchronize with exterior cells leading, though incorporating heterogeneous cell properties can allow interior cells to lead. The model islet can also be forced to oscillate at both faster and slower frequencies using periodic pulses of higher K+ in the medium surrounding the islet. Phase plane analysis was used to understand the synchronization mechanism. The results of our model suggest that diffusion of extracellular K+ may contribute to coupling and synchronization of electrical oscillations in beta-cells within an islet. PMID- 8218891 TI - Effects of electric field on alamethicin bound at the lipid-water interface: a molecular mechanics study. AB - A systematic molecular mechanics study of the alamethicin molecule was made to determine a set of low-energy conformers in vacuo and in aqueous environment. The behavior of these conformers was investigated at the phase boundary which was modeled as a plane dividing two compartments with solvation properties of water and octanol with a constant electric field applied normal to the boundary. The calculations were performed with a molecular mechanics program for calculation of stable conformations at the phase boundary utilizing the Empiric Conformational Energy Program for Peptides force field and the Hopfinger-Scheraga solvation model. 371 minimum energy conformers of alamethicin, determined in vacuo with the build-up procedure, were used as starting conformations for energy minimization in aqueous environment and at the phase boundary. Only 49 interphase-bound structures were within 12 kcal/mol of the minima which was found. No helical structures having values close to the canonical parameters for an alpha- or 3(10) helix were found despite the presence of eight alpha-methylalanine residues which favor the formation of these helices; four helix-like structures were found, having all negative phi, psi values. All the helical conformers have very high energies in water (approximately 14 kcal/mol), but are quite stable at the phase boundary (3.7-6.8 kcal/mol above the lowest minima found). The implications of these results for proposed mechanisms for membrane-binding and voltage-dependent gating are considered. PMID- 8218892 TI - Lateral diffusion in model membranes is independent of the size of the hydrophobic region of molecules. AB - We have systematically investigated the probe size and shape dependence of lateral diffusion in model dimyristoyl phosphatidylcholine membranes. Linear hydrophobic polymers, which differ in length by an order of magnitude, were used to explore the effect on the lateral diffusion coefficient of hydrodynamic restrictions in the bilayer interior. The polymers employed are isoprenoid alcohols--citronellol, solanesol, and dolichol. Tracer lateral diffusion coefficients were measured by fluorescence photobleaching recovery. Despite the large difference in lengths, the nitrobenzoxadiazole labelled alcohols all diffuse at the rate of lipid self-diffusion (5.0 x 10(-12) m2 s-1, 29 degrees C) in the liquid crystal phase. Companion measurements in isotropic polymer solution, in gel phase lipid membranes and with nonpolar fluorescent polyaromatic hydrocarbons, show a marked dependence of the lateral diffusion coefficient on the probe molecule size. Our results in the liquid crystal phase are in accord with free area theory which asserts that lateral diffusion in the membrane is restricted by the surface-free area. Probe molecules which are significantly longer than the host phospholipid, seven times longer in the case of dolichol, are still restricted in their lateral motion by the surface properties of the bilayer in the liquid crystal phase. Fluorescence quenching experiments indicate that the nitrobenzoxadiazole label does not reside at the aqueous interface, although it must reside in close proximity according to the diffusion measurements. PMID- 8218893 TI - Cross-bridge scheme and force per cross-bridge state in skinned rabbit psoas muscle fibers. AB - The rate and association constants (kinetic constants) which comprise a seven state cross-bridge scheme were deduced by sinusoidal analysis in chemically skinned rabbit psoas muscle fibers at 20 degrees C, 200 mM ionic strength, and during maximal Ca2+ activation (pCa 4.54-4.82). The kinetic constants were then used to calculate the steady state probability of cross-bridges in each state as the function of MgATP, MgADP, and phosphate (Pi) concentrations. This calculation showed that 72% of available cross-bridges were (strongly) attached during our control activation (5 mM MgATP, 8 mM Pi), which agreed approximately with the stiffness ratio (active:rigor, 69 +/- 3%); active stiffness was measured during the control activation, and rigor stiffness after an induction of the rigor state. By assuming that isometric tension is a linear combination of probabilities of cross-bridges in each state, and by measuring tension as the function of MgATP, MgADP, and Pi concentrations, we deduced the force associated with each cross-bridge state. Data from the osmotic compression of muscle fibers by dextran T500 were used to deduce the force associated with one of the cross bridge states. Our results show that force is highest in the AM*ADP.Pi state (A = actin, M = myosin). Since the state which leads into the AM*ADP.Pi state is the weakly attached AM.ADP.Pi state, we confirm that the force development occurs on Pi isomerization (AM.ADP.Pi --> AM*ADP.Pi). Our results also show that a minimal force change occurs with the release of Pi or MgADP, and that force declines gradually with ADP isomerization (AM*ADP -->AM.ADP), ATP isomerization (AM+ATP- >AM*ATP), and with cross-bridge detachment. Force of the AM state agreed well with force measured after induction of the rigor state, indicating that the AM state is a close approximation of the rigor state. The stiffness results obtained as functions of MgATP, MgADP, and Pi concentrations were generally consistent with the cross-bridge scheme. PMID- 8218894 TI - Study of wild type and genetically modified reaction centers from Rhodobacter capsulatus: structural comparison with Rhodopseudomonas viridis and Rhodobacter sphaeroides. AB - Reaction centers from the purple bacterium Rhodobacter (Rb.) capsulatus and from two mutants ThrL226-->Ala and IleL229-->Ser, modified in the binding protein pocket of the secondary quinone acceptor (QB), have been studied by flash-induced absorbance spectroscopy. In ThrL226-->Ala, the binding affinities for endogenous QB (ubiquinone 10) and UQ6 are found to be two to three times as high as the wild type. In contrast, in IleL229-->Ser, the binding affinity for UQ6 is decreased about three times compared to the wild type. In ThrL226-->Ala, a markedly increased sensitivity (approximately 30 times) to o-phenanthroline is observed. In Rhodopseudomonas viridis, where Ala is naturally in position L226, the sensitivity to o-phenanthroline is close to that observed in ThrL226-->Ala. We propose that the presence of Ala in position L226 is responsible for the high sensitivity to that inhibitor. The pH dependencies of the rate constants of P+QB- (kBP) charge recombination kinetics (P is a dimer of bacteriochlorophyll, and QB is the secondary quinone electron acceptor) show destabilization of QB- in ThrL226-->Ala and IleL229-->Ser, compared to the wild type. At low pH, similar apparent pK values of protonation of amino acids around QB- are measured in the wild type and the mutants. In contrast to Rb. sphaeroides, in the wild type Rb. capsulatus, kBP substantially increases in the pH range 7-10. This may reflect some differences in the respective structures of both strains or, alternatively, may be due to deprotonation of TyrL 215 in Rb. capsulatus. At pH 7, measurements of the rate constant of QA to QB electron transfer reveal a threefold greater rate in the reaction centers from wild type Rb. capsulatus (65 +/- 1 0 ps)-1 compared to Rb. sphaeroides.We suggest that this may arise from a 0.7-A smaller distance between the quinones in the former strain. Our spectroscopic data on the wild type Rb. capsulatus reaction center suggest the existence of notable differences with the Rb. sphaeroides reaction center structure. PMID- 8218895 TI - Probing membrane potential with nonlinear optics. AB - The nonlinear optical phenomenon of second harmonic generation is shown to have intrinsic sensitivity to the voltage across a biological membrane. Our results demonstrate that this second order nonlinear optical process can be used to monitor membrane voltage with excellent signal to noise and other crucial advantages. These advantages suggest extensive use of this novel approach as an important new tool in elucidating membrane potential changes in biological systems. For this first demonstration of the effect we use a chiral styryl dye which exhibits gigantic second harmonic signals. Possible mechanisms of the voltage dependence of the second harmonic signal are discussed. PMID- 8218896 TI - Bending stiffness of lipid bilayers: IV. Interpretation of red cell shape change. AB - Two mechanisms are operative when the resting shape of human red cells is changed into an echinocyte or a stomatocyte. The first (bilayer couple) is a differential change in the surface area of the two monolayers. It rests on the two-dimensional isotropic elasticity of the two monolayers and their fixed distance. The second (single layer) is a change in the average cone angle of the molecules comprising a monolayer. It rests on the intrinsic bending elasticity of each single layer. With a few exceptions the first mechanism has been quoted to interpret experimentally observed shape changes. To reconsider this preference two types of spontaneous curvatures (in bilayer couple bending and in single-layer bending) are defined. It is shown that (a) disregarding the single-layer mechanism is not justified and (b) there is too little basic information for quantitative interpretations of shape change. PMID- 8218897 TI - Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament. AB - Equilibrium titrations and kinetic experiments were used to define the cooperative binding of myosin subfragment 1 (S1) to actin-troponin-tropomyosin. Both types of experiment require an equilibrium between two states of the thin filament in which one state (the off state) binds S1 less readily than the other. Equilibrium titrations are compatible with > 95% of the actin7.Tn.Tm units being in the off state in the absence of calcium and 80% in the off state in the presence of calcium. Kinetic binding data suggest that the presence of calcium switches the thin filament from 70% in the off state to < 5%. The two experiments, therefore, define quite different populations of the off states. We propose a three-state model of the thin filament. A "blocked state" which is unable to bind S1, a "closed state" which can only bind S1 relatively weakly and an "open state" in which the S1 can both bind and undergo an isomerization to a more strongly bound rigor-like conformation. The equilibrium between the three states is calcium-dependent; KB = [closed]/[blocked] = 0.3 and > or = 16 and KT = [open]/[closed] = 0.09 and 0.25 in the absence and presence of calcium, respectively. This model can account for both types of experimental data. PMID- 8218898 TI - Opening and closing transitions for BK channels often occur in two steps via sojourns through a brief lifetime subconductance state. AB - Single channel currents were recorded with microsecond time resolution from large conductance calcium-activated K+ channels to examine the details of the opening and closings transitions. Analysis of averaged closing transitions indicated that the initial average conductance step for closing was to the 90-95% closed channel current level. Averaged brief closings (approximately 50 microseconds) reopened from the initial 90-95% level, whereas averaged longer closings (> 300 microseconds) closed completely from this level over the next 50-100 microseconds. The 90-95% initial closed level in the averaged current records resulted typically from the average of both complete and partial closings. From 45-80% of the initial closings were complete and 20-55% were to brief lifetime (approximately 50 microseconds) subconductance levels at 65-90% of the completely closed level. Averaged opening transitions were typically mirror images of averaged closing transitions. To extend the analysis to the very brief conductance changes that underlie the flickers of the single channel current toward the closed current level, flickers, brief closings, and longer closings were averaged separately and their slopes compared. The slopes were similar (within the 3% resolution of the method), suggesting similar initial conductance steps. Similar initial closing properties for both the briefer and longer closings would be expected if the channel first passed through the kinetic and subconductance states associated with the briefer closings (including flickers) before entering the longer closed states. Such transitions would provide an explanation for the observation that openings and closings often occur in two steps. PMID- 8218899 TI - Fast and slow inactivation of sodium channels: effects of photodynamic modification by methylene blue. AB - Illumination of crayfish giant axons, during internal perfusion with 0.5 mM methylene blue (MB), produces photodynamic effects that include (i) reduction in total sodium conductance, (ii) shifting of the steady-state inactivation curve to the right along the voltage axis, (iii) reduction in the effective valence of steady-state inactivation and, (iv) potentially complete removal of fast inactivation. Additionally, the two kinetic components of fast inactivation in crayfish axons are differentially affected by MB+light. The intercept of the faster component (tau h1) is selectively reduced at shorter MB+light exposure times. Neither tau h1 nor the slower (tau h2) process was protected from MB+light by prior steady-state inactivation of sodium channels. However, carotenoids provide differing degrees of protection against each of the photodynamic actions listed above, suggesting that the four major effects of MB+light are mediated by changes occurring within different regions of the sodium channel molecule. PMID- 8218900 TI - Voltage and temperature dependence of single K+ channels isolated from canine cardiac sarcoplasmic reticulum. AB - The temperature and voltage dependence of gating and conductance of sarcoplasmic reticulum K+ channels (S-R K+) isolated from adult canine hearts were studied using the reconstituted bilayer technique. Fusion of vesicles from this preparation frequently resulted in the incorporation of a single channel. Only bilayers into which a single S-R K+ channel had fused were studied. The three conductance states of the channel, fully open (O2), substate conductance (O1), and closed (C) were studied as a function of voltage (-50 to +50 mV) and temperature (16 to 37 degrees C). Permeation through the O1 state showed the same temperature dependence as the O2 state corresponding to an enthalpy of permeation of 4.1-4.2 kcal/mol, which is similar to that for K+ diffusion through water. As expected, increased temperature increased the frequency of gating transitions and shortened the average dwell time spent in any conductance state. Over the range of 25 to 37 degrees C, the average dwell time spent in the O1, O2, and C states decreased by 44 +/- 11, 36 +/- 13, and 78 +/- 7% (n = 3 to 4 channels), respectively. The ratio of probabilities between the various conductance states was not strongly temperature sensitive. Analysis of the voltage dependence of this channel was carried out at 37 degrees C and revealed that the dwell times of the O1 and O2 states were voltage insensitive and the probability ratio (PO2:PO1) was approximately 7 and was voltage insensitive. Nonlinear least-squares analysis of dwell times revealed that the closed state was biexponential and was thus composed of a fast (Cf) and a slow (C8) component.Tcf was voltage insensitive with an average value of 5.9 ms, whereas tau c was approximately two orders of magnitude slower and was voltage dependent. The voltage dependence of Cs was described by Tau c (ms) = exp(-0.025-(Vm (mV) - 250)). PMID- 8218901 TI - The role of hydrodynamic interaction in the locomotion of microorganisms. AB - A general Boundary Element Method is presented and benchmarked with existing Slender Body Theory results and reflection solutions for the motion of spheres and slender bodies near plane boundaries. This method is used to model the swimming of a microorganism with a spherical cell body, propelled by a single rotating flagellum. The swimming of such an organism near a plane boundary, midway between two plane boundaries or in the vicinity of another similar organism, is investigated. It is found that only a small increase (less than 10%) results in the mean swimming speed of an organism swimming near and parallel to another identical organism. Similarly, only a minor propulsive advantage (again, less than 10% increase in mean swimming speed) is predicted when an organism swims very close and parallel to plane boundaries (such as a microscopic plate and (or) a coverslip, for example). This is explained in terms of the flagellar propulsive advantage derived from an increase in the ratio of the normal to tangential resistance coefficients of a slender body being offset by the apparently equally significant increase in the cell body drag. For an organism swimming normal to and toward a plane boundary, however, it is predicted that (assuming it is rotating its flagellum, relative to its cell body, with a constant angular frequency) the resulting swimming speed decreases asymptotically as the organism approaches the boundary. PMID- 8218903 TI - Post-repolarization block of cardiac sodium channels by saxitoxin. AB - Phasic block of rat cardiac Na+ current by saxitoxin was assessed using pulse trains and two-pulse voltage clamp protocols, and the results were fit to several kinetic models. For brief depolarizations (5 to 50 ms) the depolarization duration did not affect the rate of development or the amplitude of phasic block for pulse trains. The pulse train data were well described by a recurrence relation based upon the guarded receptor model, and it provided rate constants that accurately predicted first-pulse block as well as recovery time constants in response to two-pulse protocols. However, the amplitudes and rates of phasic block development at rapid rates (> 5 Hz) were less than the model predicted. For two pulse protocols with a short (10 ms) conditioning step to -30 mV, block developed only after repolarization to -150 mV and then recovered as the interpulse interval was increased. This suggested that phasic block under these conditions was caused by binding with increased affinity to a state that exists transiently after repolarization to -150 mV. This "post-repolarization block" was fit to a three-state model consisting of a transient state with high affinity for the toxin, the toxin bound state, and the ultimate resting state of the channel. This model accounted for the biphasic post-repolarization block development and recovery observed in two-pulse protocols, and it more accurately described phasic block in pulse trains. The transient state after repolarization was predicted to have a dwell time of 570 ms, an on rate for saxitoxin of 16 s-1 micro M-1, and an off rate of 0.2 s-1 (KD = 12 nM). These results and the proposed model suggest a novel variation on phasic block mechanisms and suggest a long-lived transient Na+ channel conformation during recovery. PMID- 8218902 TI - Activation of the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum by palmitoyl carnitine. AB - Studies of [3H]ryanodine binding, 45Ca2+ efflux, and single channel recordings in planar bilayers indicated that the fatty acid metabolite palmitoyl carnitine produced a direct stimulation of the Ca2+ release channel (ryanodine receptor) of rabbit and pig skeletal muscle junctional sarcoplasmic reticulum. At a concentration of 50 microM, palmitoyl carnitine (a) stimulated [3H]ryanodine binding 1.6-fold in a competitive manner at all pCa in the range 6 to 3; (b) released approximately 65% (30 nmol) of passively loaded 45Ca2+/mg protein; and (c) increased 7-fold the open probability of Ca2+ release channels incorporated into planar bilayers. Neither carnitine nor palmitic acid could reproduce the effect of palmitoyl carnitine on [3H]ryanodine binding, 45Ca2+ release, or channel open probability. 45Ca2+ release was induced by several long-chain acyl carnitines (C14, C16, C18) and acyl coenzyme A derivatives (C12, C14, C16), but not by the short-chain derivative C8 or by free saturated fatty acids of chain length C8 to C18, at room temperature or 36 degrees C. This newly identified interaction of esterified fatty acids and ryanodine receptors may represent a pathway by which metabolism of skeletal muscle could influence intracellular Ca2+ and may be responsible for the pathophysiology of disorders of beta-oxidation such as carnitine palmitoyl transferase II deficiency. PMID- 8218904 TI - The Ca(2+)-induced conformational change of gelsolin is located in the carboxyl terminal half of the molecule. AB - We have purified the two functionally distinct domains of gelsolin, a Ca(2+) dependent actin binding protein, by proteolytic cleavage and characterized their size and shape in solution by dynamic light scattering. In the absence of calcium we obtained the same translational diffusion coefficient for both fragments which are of approximately equal molecular mass. The frictional ratio fo/fexp (1.33 1.39) is similar to the value as obtained for intact gelsolin (1.37) in aqueous solution (Patkowski, A., J. Seils, H. Hinssen, and T. Dorfmuller. 1990. Biopolymers. 30:427-435), indicating a similar molecular shape for the native protein as well as for the two subdomains. Upon addition of Ca2+ the translational diffusion coefficient of the carboxyl-terminal half decreased by almost 10%, while there was no change observed for the amino terminus. This result indicates that the ligand-induced conformational change as seen for intact gelsolin is probably located on the carboxyl-terminal domain of the protein. Since gelsolin has binding sites in both domains, and the isolated amino terminus binds and severs actin in a calcium-independent manner, our results suggests that the structural transition in the carboxyl-terminal part of intact gelsolin also affects the actin binding properties of the amino-terminal half. PMID- 8218905 TI - Spectroscopic characterization of a newly isolated cytochrome P450 from Rhodococcus rhodochrous. AB - Cytochrome P450 (P450) from Rhodococcus rhodochrous have been characterized through circular dichroism and nuclear magnetic resonance (NMR) spectroscopy, both in the substrate-free and substrate-bound forms. The data are compared with those of P450cam and indicate a close similarity of the structure of the active site in the two proteins. The substrate-free species contains low-spin iron(III), while the 2-ethoxyphenol bound species contains high-spin iron(III). The substrate is in slow exchange on the NMR time scale. The binding of CN- has been investigated and the final adduct characterized through NMR spectra. Nuclear relaxation times of the isotropically shifted signals turn out to be shorter than in other heme proteins, both in the high- and in the low-spin species. This is the result of longer electron relaxation times in P450s than in peroxidases and metmyoglobin. This property, as well as the electron paramagnetic resonance (EPR) spectrum of the substrate-free form, are discussed in terms of the presence of the cysteine as the fifth ligand of the iron ion instead of a histidine as it occurs in peroxidases and myoglobin. PMID- 8218906 TI - Effects of pressure on equatorial x-ray fiber diffraction from skeletal muscle fibers. AB - When skeletal muscle fibers are subjected to a hydrostatic pressure of 10 MPa (100 atmospheres), reversible changes in tension occur. Passive tension from relaxed muscle is unaffected, rigor tension rises, and active tension falls. The effects of pressure on muscle structure are unknown: therefore a pressure resistant cell for x-ray diffraction has been built, and this paper reports the first study of the low-angle equatorial patterns of pressurized relaxed, rigor, and active muscle fibers, with direct comparisons from the same chemically skinned rabbit psoas muscle fibers at 0.1 and 10 MPa. Relaxed and rigor fibers show little change in the intensity of the equatorial reflections when pressurized to 10 MPa, but there is a small, reversible expansion of the lattice of 0.7 and 0.4%, respectively. This shows that the order and stability of the myofilament lattice is undisturbed by this pressure. The rise in rigor tension under pressure is thus probably due to axial shortening of one or more components of the sarcomere. Initial results from active fibers at 0.1 MPa show that when phosphate is added the lattice spacing and equatorial intensities change toward their relaxed values. This indicates cross-bridge detachment, as expected from the reduction in tension that phosphate induces. 10 MPa in the presence of phosphate at 11 degrees C causes tension to fall by a further 12%, but not change is detected in the relative intensity of the reflections, only a small increase in lattice spacing. Thus pressure appears to increase the proportion of attached cross-bridges in a low-force state. PMID- 8218907 TI - Actinic light density dependence of the bacteriorhodopsin protocycle. AB - The photocycle of bacteriorhodopsin (BR) was studied in the 0.3 microsecond to 10 s time interval after excitation, using a wide range of actinic light intensities (10 ns half-duration, 0.06-60 mJ/cm2), at neutral and alkaline pH values. The relative weights of the rapidly and the slowly decaying components of the M intermediate (Mf and M(s), respectively) and the yield of the third millisecond component, N(R,P), are the function of the exciting light intensity (density), while their lifetimes are not. The relative weight of M(s) is found to be a linear function of the portion of the BR molecules undergoing the photocycle. This suggests the existence of a cooperative interaction of the BR molecules arranged in the crystalline purple membrane sheets. Another source of M(s) is also found, which results a nonvanishing relative weight of M(s) even at very weak actinic light density values. The explanation for this may be a branching, or the heterogeneity of BR itself or with its environment. It is shown that the relative weights of the rising and decaying components of the M form(s) do not correlate directly with each other. PMID- 8218908 TI - The dynamic nonlinear behavior of fly photoreceptors evoked by a wide range of light intensities. AB - Fly photoreceptor cells were stimulated with steps of light over a wide intensity range. First- and second-order Volterra kernels were then computed from sequences of combined step responses. Diagonal values of the second-order Volterra kernels were much greater than the off-diagonal values, and the diagonal values were roughly proportional to the corresponding first-order kernels, suggesting that the response could be approximated by a static nonlinearity followed by a dynamic linear component (Hammerstein model). The amplitudes of the second-order kernels were much smaller in light-adapted than in dark-adapted photoreceptors. Hammerstein models constructed from the step input/output measurements gave reasonable approximations to the actual photoreceptor responses, with light adapted responses being relatively better fitted. However, Hammerstein models could not account for several features of the photoreceptor behavior, including the dependence of the step response shape on step amplitude. A model containing an additional static nonlinearity after the dynamic linear component gave significantly better fits to the data. These results indicate that blowfly photoreceptors have a strong early gain control nonlinearity acting before the processes that create the characteristic time course of the response, in addition to the nonlinearities caused by membrane conductances. PMID- 8218909 TI - Charged local anesthetics block ionic conduction in the sheep cardiac sarcoplasmic reticulum calcium release channel. AB - We have examined the effect of the charged local anesthetics QX314, QX222, and Procaine on monovalent cation conduction in the Ca2+ release channel of the sheep cardiac sarcoplasmic reticulum. All three blockers only affect cation conductance when present at the cytoplasmic face of the channel. QX222 and Procaine act as voltage-dependent blockers. With 500 Hz filtering, this is manifest as a relatively smooth reduction in single-channel current amplitude most prominent at positive holding potentials. Quantitative analysis gives an effective valence of approximately 0.9 for both ions and Kb(0)s of 9.2 and 15.8 mM for QX222 and Procaine, respectively. Analysis of the concentration dependence of block suggests that QX222 is binding to a single site with a Km of 491 microM at a holding potential of 60 mV. The use of amplitude distribution analysis, with the data filtered at 1 to 2 kHz, reveals that the voltage and concentration dependence of QX222 block occurs largely because of changes in the blocker on rate. The addition of QX314 has a different effect, leading to the production of a substate with an amplitude of approximately one-third that of the control. The substate's occurrence is dependent on holding potential and QX314 concentration. Quantitative analysis reveals that the effect is highly voltage dependent, with a valence of approximately 1.5 caused by approximately equal changes in the on and off rates. Kinetic analysis of the concentration dependence of the substate occurrence reveals positive cooperativity with at least two QX314s binding to the conduction pathway, and this is largely accounted for by changes in the on rate. A paradoxical increase in the off rate at high positive holding potentials and with increasing QX314 concentration at 80 mV suggests the existence of a further QX314-dependent reaction that is both voltage and concentration dependent. The substate block is interpreted physically as a form of partial occlusion in the vestibule of the conduction pathway giving a reduction in single-channel current by electrostatic means. PMID- 8218910 TI - Resting myoplasmic free calcium in frog skeletal muscle fibers estimated with fluo-3. AB - Fluo-3 is an unusual tetracarboxylate Ca2+ indicator. For recent lots supplied by Molecular Probes Inc. (Eugene, OR), FMAX, the fluorescence intensity of the indicator in its Ca(2+)-bound form, is approximately 200 times that of FMIN, the fluorescence intensity of the indicator in its Ca(2+)-free form. (For earlier lots, impurities may account for the smaller reported values of FMAX/FMIN, 36 40). We have injected fluo-3 from a high-purity lot into intact single fibers from frog muscle and measured the indicator's absorbance and fluorescence signals at rest (A and F, respectively) and changes in absorbance and fluorescence following action potential stimulation (delta A and delta F signals substantially lagged behind that of the myoplasmic free Ca2+ transient. Our analysis of fluo 3's signals from myoplasm therefore focused on information about the level of resting myoplasmic free [Ca2+] ([Ca2+]r). From A, delta A, and in vitro estimates of fluo-3's molar extinction coefficients, the change in the fraction of fluo-3 in the Ca(2+)-bound form during activity (delta f) was estimated. From delta f, delta F, and F, the fraction of the indicator in the Ca(2+)-bound form in the resting fiber (fr) was estimated by fr = (delta f x F/delta F) + (1-FMAX/FMIN)-1. Since FMAX/FMIN is large, the contribution of the second term to the estimate of fr is small. At 16 degrees C, the mean value (mean +/- S.E.) of fr was 0.086 +/- 0.004 (N = 15). From two estimates of the apparent dissociation constant of fluo 3 for Ca2+ in the myoplasm, 1.09 and 2.57 microM, the average value of [Ca2+]r is calculated to be 0.10 and 0.24 microM, respectively. The smaller of these estimates lies near the upper end of the range of values for [Ca2+]r in frog fibers (0.02-0.12 microM) estimated by others with aequorin and Ca(2+)-selective electrodes. The larger of the estimates lies within the range of values (0.2-0.3 microM) previously estimated in this laboratory with fura red. We conclude that [Ca2+]r in frog fibers is at least 0.1 microM and possibly as large as 0.3 microM. PMID- 8218911 TI - Activation of Na-Ca exchange current by photolysis of "caged calcium". AB - Intracellular photorelease of Ca2+ from "caged calcium" (DM-nitrophen) was used to investigate the Ca(2+)-activated currents in ventricular myocytes isolated from guinea pig hearts. The patch-clamp technique was applied in the whole-cell configuration to measure membrane current and to dialyze the cytosol with a pipette solution containing the caged compound. In the presence of inhibitors for Ca2+, K+, and Na+ channels, concentration jumps of [Ca2+]i induced a rapidly activating inward Na-Ca exchange current which then decayed slowly (tau approximately 500 ms). The initial peak of the inward current and the time-course of current decay were voltage-dependent, and no reversal of the current direction was found between -100 and +100 mV. The observed shallow voltage dependence can be described in terms of the movement of an apparently fractional elementary charge (+0.44e-) across an energy barrier located symmetrically in the electrical field of the membrane. The currents were dependent on extracellular Na+ with a half-maximal activation at 73 mM and a Hill coefficient of 2.8. No change of membrane conductance was activated by the Ca2+ concentration jump when extracellular Na+ was completely replaced by Li+ or N-methyl-D-glucamine (NMG) or when the Na-Ca exchange was inhibited by extracellular Ni2+, La3+, or dichlorobenzamil (DCB). The velocity of relengthening after a twitch induced by photorelease of Ca2+ was only reduced drastically when both the sarcoplasmic reticulum and the Na-Ca exchange were inhibited suggesting that all other Ca2+ removing mechanisms have a low transport capacity under these conditions. In conclusion, we have used a novel approach to study Na-Ca exchange activity with photolysis of "caged" calcium. We found that in guinea pig heart muscle cells the Na-Ca exchange is a potent mechanism for Ca2+ extrusion, is weakly voltage dependent (118 mV for e-fold change) and can be studied without contamination with other Ca(2+)-activated currents. PMID- 8218912 TI - Characterization of a caldesmon fragment that competes with myosin-ATP binding to actin. AB - The protein caldesmon inhibits actin-activated ATP hydrolysis of myosin and inhibits the binding of myosin.ATP to actin. A fragment isolated from a chymotryptic digest of caldesmon contains features of the intact molecule that make it useful as a selective inhibitor of the binding of myosin.ATP complexes to actin without having the complexity of binding to myosin. The COOH-terminal 20 kDa region of caldesmon binds to actin with one-sixth the affinity of caldesmon with a stoichiometry of binding of one fragment per two actin monomers. This contrasts with the 1:6-9 stoichiometry of intact caldesmon. The binding of the 20 kDa fragments to actin is totally reversed by Ca(2+)-calmodulin and, like intact caldesmon, the 20 kDa fragments are competitive with the binding of myosin subfragments to actin. This competition with myosin binding is largely responsible for the inhibition of ATP hydrolysis, although both the fragments and intact caldesmon also reverse the potentiation of ATPase activity caused by tropomyosin. These polypeptides are useful both in defining the function of caldesmon and in studying the role of weakly bound cross-bridges in muscle. PMID- 8218913 TI - Effects of magnesium sulfate on an unfolding step of human cyanomet myoglobin. AB - The effects of magnesium sulfate (MgSO4) on an unfolding step of human cyanomet myoglobin (Mb) were examined for wild-type and three L-->A mutant Mbs. The unfolding was induced at acidic pH (3.6-4.5) with various concentrations of MgSO4 (0-2 M). The monophasic process was monitored by visible absorption spectroscopy. We observed quite nonlinear delta G not equal to-[MgSO4] relations for all the Mbs. delta G not equal to-[MgCl2] relations were also determined for a comparative study. Thermodynamic evaluation of the results indicated that an upward reflection of delta G not equal to-[MgSO4] relations in high [MgSO4] is caused by the strong Hofmeister effect of the salt. Results obtained for three mutants (L29A, L72A, and L104A) at pH 4.0 and 4.5 were consistent with our previous observation that the structure of the transition state is determined by the stability of Mb cores in the balance with the pH conditions of unfolding (T. Konno and I. Morishima. 1993. Biochim. Biophys. Acta. 1162:93-98). PMID- 8218914 TI - Evidence of an associative intermediate on the myoglobin refolding pathway. AB - Time-resolved small-angle x-ray scattering using the stopped-flow method has been applied successfully to investigate the refolding of myoglobin. This is the only method to date that yields direct information on protein physical dimensions during the folding process. It has the potential to detect and probe important processes, such as protein compaction and association, on a millisecond time scale. Initial experiments were performed with horse myoglobin denatured in high concentrations of urea. The denatured protein was diluted rapidly into a buffer containing no urea or low concentrations of urea. The time-course of the forward scattered intensity shows a decrease in amplitude which is clearly not engendered by the compaction of the protein, but does correspond well to a dimer dissociation process. Initial and final radii of gyration correspond well to a dimer and a monomer, respectively. Kratky plots of the initial and final states also support the transient dimerization model. The apparent dissociation rate constant was obtainable directly from the data. An association rate constant and an equilibrium constant could be estimated. The dimerizing intermediate is speculated to be a globular non-native state with an exposed hydrophobic surface. PMID- 8218915 TI - Global analysis of steady-state polarized fluorescence spectra using trilinear curve resolution. AB - Global analysis using trilinear curve resolution is described and shown to be a powerful method for the resolution of polarized fluorescence data arrays, in which the measured fluorescence intensity is a separable function of polarization orientation, excitation wavelength, and emission wavelength. This methodology is applicable to mixtures the components of which have linearly independent excitation and emission spectra and distinct anisotropies. Normalized excitation and emission spectra of individual components can be uniquely determined without prior assumptions concerning spectral shapes (e.g., sum of Gaussians) and without the uncertainties inherent in bilinear techniques such as principal component analysis or factor analysis. The normalized excitation and emission vectors are combined with the total absorption spectrum of the multicomponent mixture to compute absolute absorption and emission spectra. The precision of this methodology is evaluated as a function of noise, overlap, relative intensity, and anisotropy difference between components using simulated mixtures of the DNA bases. The ability of this method to extract individual spectra from steady-state fluorescence data arrays is illustrated for mixtures containing two and three components. PMID- 8218916 TI - Light-induced reorientation in the purple membrane. AB - Reorientation of bacteriorhodopsin in the native purple membrane was studied by time-resolved linear dichroism spectroscopy (TRLD) over the millisecond time regime. The time responses observed in TRLD are distinctly different from the isotropic transient absorption (TA) at wavelengths in the range 550-590 nm, where the bacteriorhodopsin ground state absorbs. In contrast, the TA and TRLD responses have nearly identical time dependence at 410 and 690 nm, where the intermediates M and O, respectively, principally contribute. These results demonstrate ground-state bacteriorhodopsin reorientation triggered by the photocycle. The TRLD and TA data are analyzed to test models for reorientational motion. Rotational diffusion of ground-state bacteriorhodopsin cannot account for the details of the data. Rather, the results are shown to be consistent with a reversible reorientation of "spectator" (nonexcited) members of the bacteriorhodopsin trimer in the purple membrane in response to the photocycling member of the trimer. This response may be associated with cooperativity in the trimer. PMID- 8218917 TI - Thermodynamic, thermomechanical, and structural properties of a hydrated asymmetric phosphatidylcholine. AB - 1-Behenyl-2-lauryl-sn-glycero-3-phosphocholine (22/12 PC) belongs to a unique group of phospholipids in which the molecule has one acyl chain almost twice as long as the other. The temperature-composition phase diagram for this lipid in the range of 25-65 degrees C, and 0 to 84.3% (w/w) water has been constructed by using the isoplethal method in the heating direction and x-ray diffraction for phase identification and structure characterization. At water contents between 10.3 and 34% (w/w) and at temperatures below 43 degrees C, a single mixed interdigitated lamellar gel phase (Lm beta, [symbol: see text]) of the type described by Hui et al. (1984. Biochemistry. 23:5570-5577) and McIntosh et al. (1984. Biochemistry. 23:4038-4044) was found. A second phase consisting of bulk aqueous solution coexists with the Lm beta phase at hydration levels above 34% (w/w) water in the temperature range between 25 and 43 degrees C. Above 43 degrees C, a partially interdigitated lamellar liquid crystalline (Lp alpha) phase ([symbol: see text]) is seen in the water concentration range extending from 0 to 84.3% (w/w). The pure Lp alpha phase is found below 43% (w/w) water, while coexistence of the Lp alpha phase and the bulk aqueous solution is observed above this water concentration which marks the hydration boundary. Interestingly, the latter boundary for both Lm beta and Lp alpha phases is nearly vertical in the temperature range studied. Furthermore, the lamellar chain-melting transition temperature appears to be relatively insensitive to hydration in the range 0-85% (w/w) water. We have confirmed the identify of the Lm beta phase by constructing a 5.7-A resolution electron density profile on oriented samples by the swelling method. Temperature-induced chain melting effects an increase in lipid bilayer thickness suggesting that the Lp alpha phase has chains packed in the partially as opposed to the mixed interdigitated configuration. Unlike the symmetric phosphatidylcholines a ripple (P beta') phase was not found as an intermediate between the low and high temperature lamellar phases of 22/12 PC. The specific volume of 22/12 PC is 940 (+/- 1) microliter/g and 946 (+/- 1) microliter/g in the hydrated lamellar gel state at 28 (+/- 2) and 40 (+/- 2) degrees C, respectively, from neutral buoyancy experiments. Based on measurements of the temperature dependence of the various lattice parameters of the different phases encountered in this study the corresponding lattice thermal expansion coefficients have been measured. These are discussed and their dependence on lipid hydration is reported. PMID- 8218918 TI - Boundary element solution of macromolecular electrostatics: interaction energy between two proteins. AB - The boundary element technique is implemented to solve for the electrostatic potential of macromolecules in an ionic solution. This technique entails solving surface integral equations that are equivalent to the Poisson and the Poisson Boltzmann equations governing the electrostatic potential inside the macromolecules and and in the solvent. A simple but robust method is described for discretizing the macromolecular surfaces in order to approximate the integral equations by linear algebraic equations. Particular attention is paid to the interaction energy between two macromolecules, and an iterative procedure is devised to make the calculation more efficient. This iterative procedure is illustrated in the electron transfer system of cytochrome c and cytochrome c peroxidase. PMID- 8218919 TI - Picosecond time-resolved absorption and fluorescence dynamics in the artificial bacteriorhodopsin pigment BR6.11. AB - The picosecond molecular dynamics in an artificial bacteriorhodopsin (BR) pigment containing a structurally modified all-trans retinal chromphore with a six membered ring bridging the C11=C12-C13 positions (BR6.11) are measured by picosecond transient absorption and picosecond time-resolved fluorescence spectroscopy. Time-dependent intensity and spectral changes in absorption in the 570-650-nm region are monitored for delays as long as 5 ns after the 7-ps, 573-nm excitation of BR6.11. Two intermediates, J6.11 and K6.11/1, both with enhanced absorption to the red (> 600 nm) of the BR6.11 spectrum are observed within approximately 50 ps. The J6.11 intermediate decays with a time constant of 12 +/- 3 ps to form K6.11/1. The K6.11/1 intermediate decays with an approximately 100 ps time constant to form a third intermediate, K6.11/2, which is observed through diminished 650-nm absorption (relative to that of K6.11/1). No other transient absorption changes are found during the remainder of the initial 5-ns period of the BR6.11 photoreaction. Fluorescence in the 650-900-nm region is observed from BR6.11, K6.11/1, and K6.11/2, but no emission assignable to J6.11 is found. The BR6.11 fluroescence spectrum has a approximately 725-nm maximum which is blue shifted by approximately 15 nm relative to that of native BR-570 and is 4.2 +/- 1.5 times larger in intensity (same sample optical density). No differences in the profile of the fluorescence spectra of BR6.11 and the intermediates K6.11/1 and K6.11/2 are observed. Following ground-state depletion of the BR6.11 population, the time-resolved fluroescence intensity monitored at 725 nm increases with two time constants, 12 +/- 3 and approximately 100 ps, both of which correlate well with changes in the picosecond transient absorption data. The resonance Raman spectrum of ground-state BR6.11, measured with low-energy, 560-nm excitation, is significantly different from the spectrum of native BR-570, thus confirming that the picosecond transient absorption and picosecond time resolved fluorescence data are assignable to BR6.11 and its photoreaction alone and not to BR-570 reformed during there constitution process (<5% of the BR6.11 sample could be attributed to native BR-570).The J6.11 and K6.11 absorption and fluorescence data presented here are generally analogous to those measured for native J-625 and K-590, respectively, and therefore, the primary events in the BR6.11 photoreaction can be correlated with those in the native BR photocycle. The BR6.11 photoreaction, however, exhibits important differences including slower formation rates for J and K intermediates as well as the presence of a second K intermediate. These results demonstrate that the restricted motion in the C11=C12-C13 region of retinal found in BR6.11 does not greatly change the overall photoreaction mechanism,but does alter the rates at which processes occur. PMID- 8218920 TI - Molecular dynamics simulations of a winter flounder "antifreeze" polypeptide in aqueous solution. AB - A winter flounder antifreeze polypeptide (HPLC-6) has been studied in vacuo and in aqueous solution using molecular dynamics computer simulation techniques. The helical conformation of this polypeptide was found to be stable both in vacuum and in solution. The major stabilizing interactions were found to be the main chain hydrogen bonds, a salt-bridge interaction, and solute-solvent hydrogen bonds. A significant bending in the middle of the polypeptide chain was observed both in vacuo and in solvent at 300 K. Possible causes of the bending are discussed. From simulations of mutant polypeptide molecules in vacuo, it is concluded that the bend in the native polypeptide was caused by side chain to backbone hydrogen bond competition involving the Thr 24 side chain and facilitated by strains on the helix resulting from the Lys 18-Glu 22 salt bridge. PMID- 8218921 TI - Simulation of alpha-helix-coil transitions in simplified polyvaline: equilibrium properties and Brownian dynamics. AB - A quantitative understanding of helix-coil dynamics will help explain their role in protein folding and in folded proteins. As a contribution to the understanding, the equilibrium and dynamical aspects of the helix-coil transition in polyvaline have been studied by computer simulation using a simplified model of the polypeptide chain. Each amino acid residue is treated as a single quasi particle in an effective potential that approximates the potential of mean force in solution. The equilibrium properties examined include the helix-coil transition and its dependence on chain position and well depth at the coil-helix interface. A stochastic simulation of the Brownian motion of the chain in its solvent surroundings has been used to investigate dynamical properties. Time histories of the dihedral angles have been used to study the behavior of the helical structure. Auto and cross-correlation functions have been calculated from the time histories and from the state (helix or coil) functions of the residues with relaxation times of tens to hundreds of picoseconds. Helix-coil rate constants of tens of ns-1 were found for both directions of the transition. PMID- 8218922 TI - Molecular dynamics simulations of poly(dA).poly(dT): comparisons between implicit and explicit solvent representations. AB - The program AMBER 3.0 has been used to generate molecular dynamics trajectories of a poly(dA).poly(dT) decamer. The simulations were performed using different methods to treat solvent effects. Results of a simulation including 18 counterions NH4+ and 4109 water molecules under (N, P, T) conditions were compared to simulation runs with implicit solvent representation in which solvent screening effects were represented by the use of a sigmoidal distance-dependent dielectric function. In the latter case, the system was simulated under microcanonical (N, V, E) and canonical (N, V, T) conditions. For the fully hydrated system simulation, a preequilibration protocol was developed since it was observed that long and progressive periods of heating and equilibration on the overall system were necessary in order to avoid energetic collisions between the solute and the solvent molecules, leading to severe irreversible deformation of the solute. A detailed analysis of DNA conformations, sugar puckers, and stability of the hydrogen bonds, Watson-Crick and three-center H bonds, is reported. The results show that DNA remains essentially in the B conformer with a tendency in the hydrated model to adopt a slightly distorted, unwound, and stretched conformation in comparison to standard B-DNA. Concerning sugar puckers, the mean pseudorotation phases of the adenine residues are systematically higher than those of the thymine residues, except in the case of the hydrated model for which a articular behavior is observed for the adenine strand. In this case, the terminal bases oscillate between C2'-endo and O4'-endo and the central ones stay in the C3'-endo domain. The mean lifetimes of the internal Watson-Crick H-bond (A) HN6...O4(T) are also dependent on the base pairs included in the calculation, excepted for the implicit solvent simulation at constant temperature. The three center H bonds have very small mean lifetimes in all three cases of MD simulation. In the minor groove of the hydrated model, a spine of hydration is found as observed by x-ray crystallography and other theoretical simulations. On the basis of the rms deviations, it appears that the fully hydrated simulation has not reached a plateau at the end of the run, while the implicit simulation at constant energy seems to have converged. At constant temperature, very large oscillations in rms deviations are observed. PMID- 8218923 TI - On the interaction of polypeptides with bile salts or bilirubin-IX alpha. AB - Aqueous solutions formed by polypeptides, simple models of proteins, and bile salts (sodium cholate and deoxycholate, NaC and NaDC, respectively) or bilirubin IX alpha (BR) have been studied by CD measurements. They could mimic more complicated biliary systems, thus supplying a possible interpretation of the behavior of some amino acid residues in the biliary proteins. The aggregation of NaDC and NaC in water can be monitored by CD measurements. Bile salts, in submicellar and micellar form, stabilize poly(L-Lys) (PLL) in alpha-helical conformation. The alpha-helix content increases with increasing bile salt concentration and ionic strength. NaDC seems to be a slightly better stabilizing agent of the alpha-helix conformation than NaC. Models characterized by hydrogen bonds between bile salts and PLL are proposed, also resorting to previous data available on the systems formed by NaDC and poly(L-Leu-L-Leu-L-Lys) (PLLL) or poly(L-Leu-L-Leu-L-Asp) (PLLA). Binding of BR to PLL, poly(D-Lys), poly(L-Glu), PLLL, and PLLA in water has been investigated by CD spectra in order to clarify the nature of the association complexes and the mechanism of the BR enantioselective complexation. Potential energy calculations provide binding models capable of explaining the enantioselective ability of the PLL and PLLL alpha-helices toward the left- and right-handed enantiomer of BR, respectively. BR is bound to -NH2 groups of PLL and PLLL lying on a right- and left-handed spiral, respectively. These results, together with those formerly obtained for some bile salts-BR systems, indicate that the selectivity originates from a binding that involves large regions of the BR molecule and gives rise, very probably, to moderate conformational changes from the "ridge tile" structure observed in the crystals. In some cases van der Waals forces can play a crucial role in the chiral recognition of bilirubin. Moreover, possible interaction models of BR with human serum albumin are proposed on the basis of a recent x-ray crystal structure of the protein. PMID- 8218924 TI - Molecular dynamics analysis of a ribonuclease C-peptide analogue. AB - We have carried out a nanosecond molecular dynamics simulation of an analogue of the ribonuclease C-peptide in water. The overall conformation has an extended region for the first three amino acids connected to an alpha-helix for residues 4 13, and this basic structure is preserved throughout the simulation, with helical hydrogen bonds present 87% of the time, on average. The final helical hydrogen bond is spontaneously broken and re-formed several times, providing a detailed picture of such winding/unwinding events. The simulation was used to estimate the effects of internal motion on proton nuclear Overhauser effect spectroscopy (NOESY) intensities for several classes of important cross peaks. Within the helical regions, the effects of internal motion vary only a little from one residue to another for backbone-backbone cross peaks, and the relevant correlation functions reach plateau values within about 50 ps. The spectral simulations show, however, that it may be difficult to establish a close quantitative connection between NOESY cross-peak volumes and measures of helical content. PMID- 8218925 TI - Assessment of protein rotational diffusion by 13C off-resonance rotating frame spin-lattice relaxation: effect of backbone and side-chain internal motion. AB - The 13C off-resonance rotating frame spin-lattice relaxation technique is applicable to the study of protein rotational diffusion behavior in a variety of experimental situations. The original formalism of James and co-workers (1978) (J. Am. Chem. Soc. Vol. 100, pp. 3590-3594) incorporated random isotropic reorientational motion of a rigid spherical rotor with no provision for backbone or side-chain carbonyl group internal motion. Here we demonstrate that the failure to include such internal motion may lead to erroneous rotational correlation time determinations for overall reorientational motion. The effect becomes severe for protein molecular masses in excess of 100 kD. Inclusion of both backbone and side-chain carbonyl carbon internal motion, using reasonable parameters derived from the literature [R. Levy and M. Karplus (1979), Chemical Physics Letters, Vol. 65, pp. 4-11; G. Careri, P. Fasella, and E. Gratton (1975), Critical Reviews in Biochemistry, Vol. 3, pp. 141-164; G. Lipari, A. Szabo, and R. LEvy (1982), Nature, Vol. 300, pp. 197-198], plus corrections for anisotropic tumbling [C. F. Morgan, T. Schleich, G. H. Caines, and D. Michael (1990), Biopolymers, Vol. 29, pp. 469-480] and microscopic viscosity [S. H. Koenig (1980), ACS Symposium Series, Vol. 127, pp. 157-176], leads to reliable values for the correlation time describing overall protein reorientation up to molecular masses of approximately 1000 kD. PMID- 8218926 TI - Single-residue substitution in homopolypeptides: perturbative helix-coil theory at a single site. AB - Based on Lifson-Roig's helix-coil transition theory, substitution of a single heteroresidue into a homopolymer host is studied. This study models recent experiments that substitute a single amino acid into a small peptide in water [A. Chakrabartty, J. A. Schellman, and R. L. Baldwin (1991), Nature, Vol. 351, pp. 586-688]. Our formalism, which is based on a perturbation method, differs from the existing theory for sequenced polymers and is naturally analogous, hence likely to be useful, to substitution experiments in the laboratory. It is shown that the intrinsic helix propensity w is directly proportional to the equilibrium constant for the helix-coil equilibrium of a single residue in a host peptide. This intuitive new result will simplify experimental data interpretations for measurements of the helical conformation on the single amino acid level. It is also shown that substitution affects the total helicity of the host peptide according to two considerations: the helicity of the replaced residue prior to the substitution, and the sensitivity of the site, a measure of neighboring interactions. The relationship between substitution stability and thermal stability is explored. PMID- 8218927 TI - Review of the chemokine meeting the Third International Symposium of Chemotactic Cytokines. PMID- 8218928 TI - Efficacy and safety of cytokines for human therapy. Report of an EC Study Group. PMID- 8218929 TI - Involvement of interleukin 1 and interleukin 1 antagonist in pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. AB - In this review we propose that the balance between the action of interleukin 1 (IL-1) and its natural antagonist IL-1ra on the level of the insulin-producing pancreatic beta-cell may play a decisive role in the pathogenesis of insulin dependent diabetes mellitus (IDDM). We argue that IL-1 potentiated by other cytokines (tumor necrosis factor alpha, interferon gamma) is an important effector molecule involved in both early and late events in the immune-mediated process that leads to beta-cell destruction and IDDM. We also point out that surprisingly high molar excesses of IL-1ra over IL-1 are necessary to block the action of IL-1 on islet beta-cells compared to islet alpha-cells in vitro and in animals. We suggest that the selectivity of beta-cell destruction in IDDM may be conferred on several levels: (1) homing of beta-cell antigen specific T cells, (2) targeted delivery of cytokines by lymphocytic and monocytic cells beta-cells, (3) high molar excesses of IL-1ra over IL-1 needed to prevent IL-1 mediated beta cell toxicity, (4) increased beta-cell sensitivity to free nitric oxide and oxygen radical formation induced by IL-1 and (5) inadequate oxidative stress response by beta-cells to cytokines. Further studies are needed to establish the in vivo role of an imbalance between the amounts of IL-1 and IL-1ra produced relative to their action in the pathogenesis of IDDM. PMID- 8218930 TI - The effect of interleukin 1 alpha on acetaminophen-induced hepatotoxicity. AB - The protective effect of interleukin 1 alpha (IL-1 alpha) in mice with acetaminophen (AAP)-induced hepatitis was investigated. IL-1 alpha had a significant protective effect if given 2 or more hours (up to 24 hours) before AAP; it significantly reduced mortality of mice and decreased serum transaminase level. The maximal effect was obtained with the dose of 1000 U (166 ng/kg) IL-1 alpha. Pretreatment with IL-1 significantly increased the synthesis of prostaglandin E2 (PGE2) in samples of liver tissue from AAP-treated mice, but had no effect on the synthesis of leukotriene C4 (LTC4). Pretreatment with indomethacin (IMC) did not abrogate significantly the protective effect of IL-1. Thus, the hepatoprotective effect of IL-1 alpha can not be entirely explained by the stimulation of prostaglandin (PG) synthesis. PMID- 8218931 TI - Epidermal growth factor potentiates interleukin 1 and tumor necrosis factor induced prostaglandin biosynthesis in human gingival fibroblasts. AB - The effects of and interactions between epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha) interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF-alpha) on arachidonic acid release and prostaglandin biosynthesis in human gingival fibroblasts were studied. IL-1 alpha, IL-1 beta and TNF-alpha, but not EGF nor TGF-alpha, stimulated prostaglandin E2 (PGE2) formation in the gingival fibroblasts. The effect of IL-1 alpha, IL-1 beta and TNF-alpha on PGE2 formation was significantly potentiated by EGF in a dose dependent manner. Similarly, TGF-alpha synergistically potentiated IL-1 beta stimulated PGE2 formation. IL-1 beta but not EGF stimulated the release of 3H arachidonic acid (3H-AA) from prelabelled gingival fibroblasts. In contrast to the effect on PGE2 formation, no synergistic interaction between EGF and IL-1 was seen on arachidonic acid (AA) release. Addition of unlabelled exogenous AA, in the presence of EGF, resulted in a significant increase in PGE2 formation compared to that seen in fibroblasts not exposed to EGF. The results demonstrate that EGF and IL-1 as well as EGF and TNF-alpha act in concert to enhance prostanoid formation in gingival fibroblasts. Data indicates that EGF potentiates the IL-1 and TNF-alpha induced PGE2 formation at the level of prostaglandin endoperoxide synthase (cyclooxygenase). The synergistic effects of inflammatory cytokines and growth factors may be of physiological importance for regulation of regenerative tissue growth during inflammation and repair. PMID- 8218932 TI - Differential regulation of tumour necrosis factor receptors (TNF-R) by IL-4; upregulation of P55 and P75 TNF-R on synovial joint mononuclear cells. AB - Interleukin 4 (IL-4) has previously been shown to downregulate the production of proinflammatory cytokines such as TNF-alpha, and hence has been considered to be a potential anti-inflammatory agent. In this study we have investigated the effects of IL-4 on the expression of both p55 and p75 TNF receptors (TNF-R) by flow cytometry and radioligand binding analyses and demonstrate that IL-4 downregulates both p55 and p75 TNF-R on HeLa and Jijoye cell lines in a dose dependent manner. IL-4 reduced the number of p55 TNF-R on HeLa cells from 6400 (Kd 5.1 nM) to 3900 (Kd 3.7 nM), and p75 TNF-R on Jijoye cells from 4800 (Kd 1.6 nM) to 3250 (Kd 1.5 nM). However, different effects were observed on peripheral blood mononuclear cells (PBMC). IL-4 inhibited the increase in p55 and p75 TNF-R on PBMC following adherence, whereas IL-4 upregulated p75 TNF-R expressed on PHA induced T cell blasts. To assess further the possible anti-inflammatory properties of IL-4, we studied its effects on synovial joint mononuclear cell cultures from 15 patients with inflammatory synovitis. In contrast to the differential effects of IL-4 on monocytes and T cells, IL-4 upregulated both p55 (P < 0.05) and p75 TNF-R (P < 0.005) on synovial joint cells in culture. IL-4 treatment caused a small decrease in levels of bioactive TNF-alpha in RA synovial culture supernatants, together with an increase in soluble p75 TNF-R levels although differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218933 TI - Expression and characterization of bioactive recombinant ovine TNF-alpha: some species specificity in cytotoxic response to TNF. AB - We have expressed and partially purified recombinant ovine tumour necrosis factor alpha (rovTNF-alpha) using a yeast Ty, virus like particle, expression system. RovTNF-alpha is at least as active as recombinant human TNF-alpha (rhTNF-alpha) in two different bio-assays performed on ovine material, whilst approximately 1000-fold more rovrTNF-alpha than rhTNF-alpha is required to induce the same level of cytotoxicity in TNF-sensitive murine cell lines L929 and WEHI 164 clone 13. When cytotoxic assays are performed on the porcine TNF sensitive cell line PK(15)-1512, rovTNF-alpha shows about 2 logs greater activity than on murine cells, whilst rhTNF-alpha is about 1 log more active. A monoclonal antibody, raised against rovTNF-alpha, has been used to demonstrate the presence of nanogram amounts of an appropriately sized glycoprotein to be native ovine TNF alpha in supernants of LPS stimulated ovine alveolar macrophages. These samples show no detectable cytotoxicity to L929 cells, although they show activity attributable to TNF-alpha (through neutralization by a polyclonal antiserum raised to rovTNF-alpha) in an assay on ovine material. The relative lack of activity on murine cells helps to explain previous reports of inability to assay native ovine TNF-alpha using these cells, in spite of their routine use to assay TNF-alpha from several other species. The sequence features in ovine TNF-alpha which might reduce its affinity for the murine TNF type 1 receptor are discussed. PMID- 8218934 TI - Potentiation of therapeutic effect of recombinant tumor necrosis factor against B16 mouse melanoma by combination with recombinant interleukin 2. AB - Treatment of B16 melanoma-bearing mice with recombinant tumour necrosis factor (rTNF) caused a marked inhibition of tumour growth but did not result in the complete cure of the tumour-bearing mice. In contrast, combination therapy of B16 bearing mice with r-TNF and recombinant interleukin 2 (rIL-2) potentiated the therapeutic effect of rTNF and 30% of the mice were totally cured from tumour. Spleen cells obtained from B16-bearing mice showed markedly decreased immune responses including IL-2 production, IL-2 responsiveness and mixed lymphocyte reaction owing to the existence of suppressor macrophages. However, spleen cells obtained from mice cured with rTNF plus rIL-2 showed the same level of T cell responsiveness as that from normal mice. The decreased induction of alloantigen specific cytotoxic T lymphocytes (CTL) in B16-bearing mice was also recovered after treatment with rTNF plus rIL-2. Moreover, B16-specific CTL, which could not be induced in normal or B16-bearing mice, was effectively induced from the spleen cells of B16-cured mice by rTNF and rIL-2. These results demonstrated that local therapy of melanoma with rTNF and rIL-2 was effective and induced systemic antitumour immunity in vivo. PMID- 8218935 TI - Murine interferon-gamma enhances resistance to infection with strains of Pseudomonas aeruginosa in mice. AB - This study focused on the role of recombinant murine interferon-gamma (rMuIFN gamma) in modulating resistance to infections produced by Pseudomonas aeruginosa in mice. CBA/C mice were treated with rMuIFN-gamma, exposed to thermal injury, and challenged with P. aeruginosa organisms. Survival of infected, burned mice was determined over a period of 14 days and compared with control animals not receiving rMuIFN-gamma. Two clinical isolates of P. aeruginosa that differed originally in the ability to produce metalloproteases, were used to infect the mice. When the mice were pretreated with rMuIFN-gamma before the infection, no statistically significant differences in survival were observed with either of the two strains of bacteria compared to controls. However, when mice were pretreated and injected therapeutically with rMuIFN-gamma (continued receipt of rMuIFN-gamma after infection), there was a significant protective effect in animals infected with one of the strains of P. aeruginosa. We conclude that rMuIFN-gamma may be useful in treating infections with certain strains of P. aeruginosa in mice. PMID- 8218936 TI - Evidence for nuclear phosphoinositidase C activity in the antiproliferative signals produced by interferon in Burkitt lymphoma cells. AB - The influence of interferon alpha on nuclear phosphoinositidase C (PIC) in Daudi cells has been analysed. Results showed an early increase of PIC activity detectable within 90 min of interferon treatment concomitant with an increase of diacylglcerol (DAG) levels. Since the interferon-induced DAG production is not modified by the addition of propranolol, a compound known to inhibit production of DAG from phosphatidylcholine hydrolysis, it is suggested that the interferon antiproliferative signal is transduced into the nucleus via the inositol lipid pathway. A parallel analysis performed on intact cells showed a rapid inhibition of PIC activity accompanied by an increase of DAG level thus suggesting that interferon-generated signals at plasma-membrane level use pathways different from that of inositol lipids. A selected clone of Daudi cells resistant to interferon action provided a control for specificity of results. PMID- 8218937 TI - Production of IL-3 by non-transformed primary neonatal murine keratinocytes: evidence for constitutive IL-3 gene expression in neonatal epidermis. AB - Interleukin 3 (IL-3) is a cytokine produced by activated T lymphocytes that is best understood as a hematopoietic growth and differentiation factor. Production of IL-3 by other cell types is controversial; while certain transformed non lymphocyte cell lines can produce IL-3, it is generally assumed that their non transformed counterparts do not. It has been previously reported that Pam 212, a transformed murine keratinocyte cell line, produces IL-3. In this study we report that IL-3 can also be secreted by normal murine keratinocytes. Using a cell line (FL5.12) which is responsive to IL-3 and not to other keratinocyte derived cytokines, (e.g. GM-CSF, IL-1 and IL-6), we tested conditioned media from cultures of normal neonatal keratinocytes for biologically active IL-3. These media stimulated the proliferation of FL5.12, and the effect could be neutralized by specific antibodies to IL-3. The presence of IL-3 mRNA was demonstrated by polymerase chain reaction (PCR) amplification of reverse transcribed IL-3 mRNA from cultured normal neonatal keratinocytes and confirmed by Southern blot analysis. By similar techniques, IL-3 mRNA could be identified in freshly isolated neonatal epidermis but not dermis. These data indicated that IL-3 is produced by keratinocytes in the skin of normal neonatal mice, raising the likelihood that the neonatal epidermal microenvironment may have hematopoietic or lymphopoietic properties. PMID- 8218938 TI - Fc gamma receptor-mediated biological activities of human leukemic cell lines and their modulation by transforming growth factor-beta 1 and interleukin 6. AB - Previously we reported that transforming growth factor-beta 1 (TGF-beta 1) remarkably enhanced the differentiation of human leukemic cell lines, HL-60 and THP-1, in the presence of 1 alpha,25-dihydroxyvitamin D3 (VD3) and also that it induced Fc receptor for immunoglobulin G (Fc gamma R), type IIIB, in the presence of retinoic acid (RA). The present study revealed that TGF-beta 1 enhanced the Fc gamma RI- and Fc gamma RII-mediated antibody-dependent cellular cytotoxicity (ADCC) of the cells differentiated in the presence of VD3 and RA. However, production of active oxygen molecules was suppressed by TGF-beta 1. On the other hand, IL-6 stimulated production of active oxygen molecules and ADCC of the cells treated with VD3 and tumor necrosis factor-alpha (TNF-alpha). Furthermore, the levels of cell surface Fc gamma RI and Fc gamma RII were not clearly correlated with the ADCC. The TGF-beta 1/VD3-treated HL-60 cells were able to synthesize mRNAs for TGF-beta 1 and TNF-alpha, although TNF-alpha protein was not detectable. These results suggest that TGF-beta 1 has a bifunctional role, either stimulatory or inhibitory, in the modulation of macrophage activities through Fc gamma Rs and that IL-6 stimulates certain macrophage activities in mature cells. PMID- 8218939 TI - Studies of binding and internalization of human recombinant monocyte chemotactic and activating factor (MCAF) by monocytic cells. AB - Recombinant human monocyte chemotactic and activating factor (MCAF) was iodinated and specific binding sites for this cytokine were detected on human peripheral blood monocytes, the monocytic leukemia cell line THP-1, and on PMA differentiated HL60 and U937 cell lines. The binding sites were specific for MCAF since other polypeptide cytokines and the chemotactic peptide formyl-methionyl leucyl-phenylalanine (fMLP) failed to compete for 125I-rhMCAF binding. Steady state binding experiments at 4 degrees C revealed the presence of 13,000 and 18,000 receptor sites/cell on monocytes and THP-1 cells with Kd values of 22.5 nM and 25.7 nM, respectively. Compared to a human natural MCAF, rhMCAF was less potent in inducing maximal monocyte migration. Human natural MCAF similarly competed more efficiently for 125I-rhMCAF binding than unlabelled rhMCAF. The ligand-receptor association was highly temperature-dependent, with maximal ligand uptake at 37 degrees C accompanied by internalization of the ligand-receptor complexes. The internalized 125I-MCAF was progressively degraded and released into the culture medium starting at 30 min. Lysosomotropic ammonium chloride could inhibit the degradation of this ligand suggesting the involvement of lysosomal enzymes in the proteolytic digestion. Incubation with cycloheximide did not block the rapid reappearance of MCAF receptors within 20 min on the cell surface indicative of receptor recycling rather than new protein synthesis. These data indicate that monocytic cells express specific receptors for rhMCAF which can be dynamically regulated by MCAF. PMID- 8218940 TI - Prevention and treatment of Staphylococcus aureus infections with recombinant cytokines. AB - Antibiotic therapy is only moderately efficacious for bovine Staphylococcus aureus mastitis. We have used recombinant bovine cytokines to activate the natural host defenses, to prevent and treat bovine mastitis. Uninfected mammary glands infused with GM-CSF or IL-2 increased the percentage of phagocytic cells in the milk by 2-3 fold. IL-1 increased the number of polymorphonuclear cells in the milk, enhanced their inducible oxygen radical formation, and had no effect on phagocytosis. Treatment with IL-2 increased the number of polymorphonuclear cells in the milk, enhanced their inducible oxygen radical formation, and enhanced their phagocytosis. GM-CSF had no effect on the number polymorphonuclear cells in the milk but enhanced their inducible oxygen radical formation, and enhanced their phagocytosis. All cytokines were effective in preventing S. aureus infections (20-100%). 52% of all chronically infected mammary gland quarters treated with three doses of IL-2 responded to therapy and 32% of the treated quarters remained cured. 75% of all mammary glands treated with three doses of IL 1 beta responded to therapy by clearing the infection and 22% of the treated glands remained cured. These studies demonstrate that recombinant bovine cytokines can be used effectively to prevent infections as well as treat established chronic infection. PMID- 8218941 TI - Tumour necrosis factor (TNF) binding proteins (soluble TNF receptor forms) with possible roles in inflammation and malignancy. AB - Inhibitors of Tumour Necrosis Factor (TNF) may be necessary for protection of the host against harmful systemic manifestations of this cytokine such as in the septic syndrome and inflammatory conditions. TNF-binding proteins (TNF-BP) have been identified and shown to be the soluble extracellular domains of two transmembrane TNF receptors produced by proteolytic cleavage. TNF-BP inactivates TNF by formation of high affinity complexes thereby reducing the binding of TNF to target cell membrane receptors. In addition, TNF is stabilized in complex with TNF-BP, and under certain conditions the complex may act as a slow releaser of biologically active TNF. TNF can induce the release of TNF-BP in vivo which might neutralize the bioactivity of TNF. Cytokine control by natural and recombinant cytokine inhibitors such as TNF-BP could be a promising therapeutic approach in chronic inflammatory disorders to shift the balance between a cytokine-induced response and counteracting "anticytokines". A local production of TNF-BP in some tumour tissues may inactivate TNF for the benefit of the tumour. In some leukemias e.g. B-cell chronic lymphocytic leukemia, where TNF can act as a growth factor for the malignant cells, TNF-BP may be growth inhibitory. PMID- 8218942 TI - IL-1 transduction signals. PMID- 8218943 TI - Tolerance and cerebrospinal fluid pharmacokinetics of intrathecally administered human natural interleukin-2: a phase I trial. AB - Recombinant interleukin-2 (rIL-2) is at present widely applied in the immunotherapy of various advanced cancers. As a number of side effects following the administration of rIL-2, either alone or in combination with lymphokine activated killer (LAK-) cells, have been reported, a preparation of human leukocyte-derived and fully glycosylated interleukin-2 was used in the present study. We have recently demonstrated in cats that this natural IL-2 (nIL-2) is well tolerated and that the distribution and elimination half-lifes following intrathecal (i.th.) application are considerably longer than those after intravenous (i.v.) injection. To determine whether these long half-lifes and the good tolerance of i.th. given nIL-2 are also found in man, four patients with meningeosis neoplastica received repeated injections of human nIL-2 i.th.. Cerebrospinal fluid samples were drawn at different time intervals from either the lateral ventricle or lumbar subarachnoid space. The doses of nIL-2 ranged from 2 x 10(4) to 4 x 10(5) IU per injection. Only minor side effects were noted in one patient. The half-lifes for distribution and elimination of i.th. given nIL-2 ranged between 0.5-1.7 hours and 4.9-14.4 hours respectively. A linear relationship exists between the i.th. dose of nIL-2 and the area under the cerebrospinal fluid activity time profile curve. PMID- 8218944 TI - Functional linkage of the Gro beta and IL-8 receptors on the surface of human neutrophils. AB - Gro beta and IL-8 are two pro-inflammatory cytokines with chemotactic activities on neutrophils. Binding studies were performed to ascertain whether their similar biological activities are mediated through the same receptor. Since Gro beta lacks tyrosine residues, recombinant Gro beta containing an additional carboxyterminal tyrosine residue (Gro beta-Tyr) was produced in transfected COS cells, purified to homogeneity and radiolabelled with 125INa. Saturation experiments using [125I]-Gro beta-Tyr allowed us to identify high affinity receptors on human neutrophils (Kd: 2 +/- 0.5 nM and Bmax: 4760 +/- 761 sites/cell). Experiments using [125I]-IL-8 as ligand, showed no significative differences in affinity (Kd: 4 +/- 0.9 nM) but about two times the number of sites (11316 +/- 1810 sites/cell). In competition experiments using [125I]-Gro beta-Tyr, unlabelled IL-8 and Gro beta-Tyr generated superposable displacement curves (IC50: 0.69 +/- 0.15 nM and 0.42 +/- 0.11 nM, respectively). Interesting, IL-8 binding sites could be down-regulated by Gro beta and IL-8, indicating that the two binding sites may be associated. Cross-linking experiments using [125I] IL-8 revealed two major bands at 70 and 140 kDa, whereas experiments with [125I] Gro beta-Tyr showed only the 70 kDa band. Taken together, these results suggest that the human neutrophil IL-8/Gro beta receptor is a dimeric complex with two high affinity binding sites for IL-8 and of those two, only one is shared by Gro beta. PMID- 8218945 TI - A phase I study of recombinant human interleukin-4 administered by the intravenous and subcutaneous route in patients with advanced cancer: immunological studies. AB - The effects of recombinant human interleukin-4 (rhu IL-4) on immunological parameters in patients receiving increasing doses of IL-4 in a Phase I trial were investigated. Peripheral blood mononuclear cells were phenotyped for a variety of lymphocyte markers, but no consistent effects were observed. However, increases in HLA Class II expression on monocytes were detected in four patients. NK and LAK activity were neither induced nor augmented by IL-4 treatment. Slight increases in proliferative responses to mitogens and cytokines were observed in some patients. The latter observations and other clinical studies suggest that a combination of IL-4 with IL-2 may be more effective in Phase II clinical trials. PMID- 8218946 TI - Activation pathways triggered by interleukin-4 in the human plasmacytoma cell line RPMI-8226--differences with resting B lymphocytes. AB - The early events following the ligation of interleukin-4 (IL-4) to the plasmacytoma cell line RPMI-8226 were analysed as a model of action for this interleukin on differentiated cells of the B lymphocyte lineage. The addition of recombinant IL-4 to these cells resulted in an increase of the intracytoplasmic free calcium concentration [Ca2+]i, but in contrast to normal B cells, this increase was mostly due to a calcium influx rather than to a mobilization from endoplasmic reticulum stores. IL-4 was also found to trigger cAMP accumulation in RPMI-8226 cells, with kinetics similar to that which has been described for normal resting human B lymphocytes. However, in contrast to normal B cells, IL-4 did not increase CD23 membrane expression on RPMI-8226 cells. But after incubation with high concentrations of IL-4, soluble CD23 (sCD23/IgE-BF) could be detected in the supernatant of these cells. In addition, the proliferation of RPMI-8226 cells was only moderately affected by IL-4. The expression of the receptors for IL-6, a growth factor for plasma cells, was not modified upon incubation of these cells with IL-4. These results therefore suggest that terminally differentiating B cells, such as the RPMI-8226 cell line, share common pathways of activation by IL-4 with mature resting B lymphocytes, but differ in some respects. PMID- 8218947 TI - Induction of Fc receptors on murine macrophages and leukemic cells by interleukin 1 beta. AB - Recombinant human interleukin-1 beta (rhIL-1 beta) is shown to be a strong inducer of Fc receptors (FcR) on murine macrophages and not on granulocytes. Data is provided indicating that rhIL-1 beta does induce specific but not nonspecific phagocytosis. Macrophages are shown to autoinduce their FcR expression as a function of time in culture. This induction is increased by the use of exogenous rhIL-1 beta and inhibited by anti-rhIL-1 beta antibody, pointing to an autocrine regulation of FcR expression on macrophages. On the other hand the myelomonocytic cell line WEH13BD- and the macrophage like cell line WR19M.1 are also shown to be inducible for the expression of FcR by this molecule. Data is also provided showing that recombinant murine Interferon gamma (rmIFN gamma) induces FcR on both macrophages and granulocytes. Whereas polyclonal antibodies inhibit FcR induction by IL-1 on macrophages, it does not inhibit FcR induction by IFN gamma on these cells. This points to a different mechanism of induction of FcR by IFN and IL-1. Finally, the possible application of rhIL-1 beta in vivo to help the organism fight infections is discussed. PMID- 8218948 TI - Plasmid DNA and low-frequency electromagnetic fields. AB - Physico-chemical and biological properties were studied in recombinant plasmids exposed to electric and magnetic fields (EMFs). The absence of slow-migrating DNA species and failure to identify induced DNA conformers, suggests that EMFs do not have any obvious genotoxic effect in any of the experimentally tested conditions. PMID- 8218949 TI - Phonetic rehabilitation after laryngectomy. AB - This work deals with the phonetic rehabilitation of patients after laryngectomy, describing the various types of alaryngeal voice. The rehabilitation was monitored with a computer by means of a specific voice programme which permits the registration, visualization and reproduction of each sound emitted in conjunction with the classification of the principal parameters, thus allowing the patient to check his acoustic feedback. PMID- 8218950 TI - Hypertension and diabetes mellitus. AB - The association of arterial hypertension and diabetes mellitus is frequent: one third of patients attending a diabetic clinic. Excess hypertension frequency is marked in type II, non insulin-dependent diabetes, a condition often associated with other vascular risk factors such as obesity and lipid disorders. Insulin resistance is a common feature between type II diabetes, hypertension and other risk factors. In type I, insulin-dependent diabetes, hypertension is often linked to diabetic nephropathy. There is a genetic basis for diabetic nephropathy, which may share a common background with familial hypertension. Apart from possible genetic predispositions to hypertension diabetes association, chronic hyperglycaemia can lead to alteration in functional and structural properties of blood and vessels, which both contribute to elevated vascular resistance and blood pressure. From a therapeutic viewpoint, blood pressure values above 140/90 mmHg are not tolerable in diabetic subjects under 40 years of age. Due to their renal haemodynamic effects, angiotensin I converting enzyme inhibitors may be of special interest to protect kidney function in diabetic subjects. PMID- 8218951 TI - Colony promoting activity (CPA) is a novel factor distinct from IL-6. AB - The supernatant (CM) of long-term bone marrow culture (LTBMC) contains colony promoting activity (CPA) which does not have granulocyte-macrophage (GM) colony stimulating activity but which enhances GM-colony formation in the presence of CSF. CPA is different from IL-1, IL-3 and GM, G-, and M-CSF. Since CPA-containing LTBMC-CM always contains a substantial level of IL-6, CPA was thought to be similar to IL-6. In the present study, we found that LTBMC with a particular batch of horse serum produced IL-6 without a corresponding production of CPA. Addition of IL-6 to GM-colony assay system in the presence of GM-CSF did not enhance the colony formation. LTBMC-CM did not stimulate proliferation nor differentiation of mast cell progenitors. Anti-IL-6 antibodies suppressed IL-6 activity, but not CPA. These results indicate that CPA is a novel factor distinct from IL-1, IL-3, G-, M-, GM-CSF, IL-6 and SCF (c-kit ligand). PMID- 8218952 TI - A feasible method for expansion of peripheral blood lymphocytes by culture with immobilized anti-CD3 monoclonal antibody and interleukin-2 for use in adoptive immunotherapy of cancer patients. AB - Cultivation of T lymphocytes with immobilized anti-CD3 monoclonal antibody and human recombinant interleukin-2 induced a rapid proliferative response. This procedure was applied to expansion culture of peripheral blood lymphocytes obtained from cancer patients for use in adoptive immunotherapy. Peripheral blood mononuclear cells were separated from 20 ml of blood and cultured in anti-CD3 coated flasks with rIL-2 for 6 days, then transferred to a gas-permeable culture bag and culture continued for an additional 8 days with an increasing volume of medium. Cell numbers increased about 2000-fold during this 2-week culture. The final population contained about 30% CD4+ and 60% CD8+ cells, and all were CD3+ & HLA-DR+. NK cells comprised less than 5%. In clinical trials involving 12 cases receiving 35 infusions, the mean number of harvested T cells after 14 days culture was 3.5 x 10(10) (R = 1.6-6.8 x 10(10)), and the mean expansion index was 1560-fold (R = 409-4091). This method could be of benefit not only in immunotherapy but also for obtaining somatic cells from a small volume of blood for use in molecular or genetic analysis instead of having to perform EB virus transformation of B cells. PMID- 8218953 TI - Hypolipidemic activity of boronated nucleosides and nucleotides in rodents. AB - Base-boronated nucleoside and phosphate-boronated nucleotides were potent hypolipidemic agents in rodents, lowering both serum cholesterol and triglyceride levels. Rat VLDL and LDL cholesterol levels were generally reduced and HDL cholesterol levels were significantly elevated after 14 days dosing at 8 mg/kg/day. Tissue cholesterol, triglyceride and phospholipid levels were reduced by selected derivatives. Increased fecal excretion of lipids did not appear to be a mechanism by which these derivatives lowered serum lipids in rodents. Rather, the agents suppressed appetite and reduced the activities of rate-limiting enzymes for de novo lipid synthesis, specifically cytoplasmic acetyl CoA synthetase, squalene synthetase, and phosphatidylate phosphohydrolase with IC50 values of approximately 10(-5) m. PMID- 8218954 TI - HIV-1-induced immune suppression may result from autoimmune disorders including anti-SLWDQ autoantibodies. AB - We have previously unravelled the striking SLWDQ pentapeptide identity between HIV-1 env gp120 and the CD4 molecule. We show here that this pentapeptide is required for the functioning of the co-stimulatory MHC-CD4 signal in T4-cell activation since it suppresses antigen-induced T-cell proliferation. Moreover, concerning the MHC class II counterpart, the LNGQEETGVVSTN sequence which strongly inhibits T-cell immune activation is likely to be part of the functional site of the molecule. Interestingly the MHC/gp120 homology described by Young overlaps this MHC region. We further report that the gp120 SLWDQ peptide triggers an immune reaction which is both humoral (anti-SLWDQ antibodies) and cellular (CTLs against autologous targets carrying the pentapeptide) in HIV-1 infected individuals. Finally, anti-SLWDQ antibodies from patients sera purified by column chromatography strongly inhibit antigen-induced immune T-cell activation. This result led us to postulate that these antibodies found in high titers in HIV-1 infected individuals could contribute to set up the progressive systemic immune T cell suppression characterizing AIDS. PMID- 8218955 TI - Biopharmaceutical evaluation of transnasal, sublingual, and buccal disk dosage forms of butorphanol. AB - A series of three-way crossover randomized studies were conducted to evaluate the absolute bioavailability of butorphanol, a potent agonist-antagonist analgesic, from transnasal, sublingual, and buccal disk formulations in order to identify a practical alternative to oral administration. In each study, healthy male volunteers received 2 mg doses of butorphanol tartrate intravenously and either transnasally, sublingually or buccally. Serial blood samples were collected over 12 h and butorphanol plasma concentrations were determined by radioimmunoassay. The plasma concentration data were subjected to non-compartmental pharmacokinetic analysis. The elimination half-life of butorphanol was about 3-5 h and was independent of the route of administration. Absorption of butorphanol following transnasal administration was faster than that observed following sublingual or buccal administration. Mean absolute bioavailabilities of sublingual tablet and buccal disk formulation were only 19 per cent and 29 per cent, respectively, but for transnasal administration the value rose significantly, to 70 per cent. Based on the results of these studies, transnasal dosage form of butorphanol was selected for further clinical trials of treatment of moderate to severe pain. PMID- 8218956 TI - Bioequivalence study of nalidixic acid tablets: in vitro-in vivo correlation. AB - The USP dissolution test was used to select seven products with a wide range of dissolution characteristics for in vivo examination. The bioequivalence of seven (500 mg) products was evaluated in two crossover urinary excretion experiments. In each study three products were compared with the innovator product (Negram Winthrop-Breon) in 12 subjects according to a 4 x 4 latin square design. Significantly different, lower bioavailability was observed in two products in relation to that of the innovator product. Linear in vitro-in vivo correlations were found between the cumulative amount excreted at 24 h and the log of the amount dissolved at 30 min and between log of the cumulative amount excreted up to 24 h and the log of the amount dissolved at 45 min. PMID- 8218957 TI - Effect of infusion duration on valproate pharmacokinetics. AB - The pharmacokinetics of intravenously administered valproic acid (VPA) were investigated in 16 healthy male volunteers in a single-dose, fasting, four period, randomized, double-blind, placebo-controlled, parallel design study. Subjects were randomly assigned to be infused a single dose of sodium valproate equivalent to 1000 mg VPA or placebo over each of four different time periods. Valproate concentrations in plasma were determined using gas chromatography with flame ionization detection. The pharmacokinetic parameters were determined by both non-compartmental and model-dependent techniques. Analyses of variance (ANOVAs) were performed to detect any statistical differences among the regimens. Overall, the pharmacokinetic of valproate were similar after infusions of 5, 10, 30, and 60 min, with an average terminal-phase half-life of 15.9 h. There were modest differences in overall clearances among the regimens, with the 5 min infusion producing a mean area under the plasma concentration-time curve (AUC; 1877 micrograms.h ml-1) that was significantly (13 to 16 per cent) higher than the means for the longer infusions (1614-1656 micrograms.h ml-1). Differences in distribution were also noted as a function of infusion duration. The shortest duration produced a significantly smaller terminal volume of distribution (12.8 vs 14.2-15.1 l) and more rapid tissue equilibration. The alpha-phase rate constant declined from a mean of 5.1 h-1 after the 5 min infusion to a mean of 0.9 h-1 after the 60 min infusion. The distributional differences are almost certainly related to the saturable protein binding of valproate. However, the lower clearance after the 5 min infusion indicates that there may have also been partial saturation of one of the metabolic pathways of valproate during the distributive phase, and that the increase in fu was smaller than the decrease in CL'int, such that the product of fu.CL'int showed a net decrease. PMID- 8218958 TI - Pharmacokinetics of diacerein in patients with liver cirrhosis. AB - The pharmacokinetics of diacerein following a single oral dose of 50 mg was studied in 12 healthy volunteers, 10 patients with a mild liver cirrhosis (Child Pugh's grade A), and 6 patients with a more severe liver cirrhosis (Child Pugh's grade B to C). Statistical analysis using a Kruskal-Wallis test showed no significant differences between the three groups for the following parameters: median Cmax was 3.9 mg l-1 for the cirrhotic patients group I (CPI) and 3.2 mg l 1 for the cirrhotic patients group II (CPII) versus 3.2 mg l-1 for the healthy volunteers (HV); median t1/2 was 4.9 h for CPI and 4.3 h for CPII versus 4.3 h for HV; median Cl/F was 2.1 l h-1 for CPI and 2.5 l h-1 for CPII versus 1.6 l h-1 for HV; median Vdss/F was 12.6 l for CPI and 14.0 l for CPII versus 13.21 for HV. The urinary parameters were comparable. It was concluded that, from a pharmacokinetic point of view, no reduction in the initial dosage of diacerein need be proposed in liver cirrhosis. PMID- 8218959 TI - Relative bioavailability of two disopyramide capsules in humans based on total, unbound, and unbound enantiomer concentrations. AB - The relative bioavailability of two 100-mg disopyramide formulations which showed almost an 8- to 10-fold difference in their dissolution rates at pH 1.2 and 6.8 was determined in eight healthy subjects using a randomized block design. Although no significant differences in relative bioavailability were observed between the two formulations when based on the total disopyramide concentration, an almost 30 per cent difference in the extent of bioavailability was observed when assessed in terms of the unbound (+/-)- and (-)-disopyramide concentration, due probably to stereoselective nonlinear plasma protein binding. This suggests that unbound enantiomer parameters would be more sensitive to differences in bioavailability between two disopyramide formulations. Therefore, the type of concentration used would be an important factor for precise evaluation of the relative bioavailability of racemic drugs. PMID- 8218960 TI - Inhibition of rat hepatic mitochondrial aldehyde dehydrogenase isozymes by repeated cyanamide administration: pharmacokinetic-pharmacodynamic relationships. AB - The inhibition of rat hepatic mitochondrial aldehyde dehydrogenase (ALDH) isozymes was studied in apparent steady-state conditions after repeated intra peritoneal cyanamide administration. The low-Km mitochondrial ALDH isozyme was more susceptible to cyanamide-induced inhibition (DI50 = 0.104 mg kg-1) than the high-Km isozyme (DI50 = 8.52 mg kg-1), with almost complete inhibition occurring at 0.35 mg kg-1 total cyanamide administered for the low-Km isozyme. The relationships between plasma and liver cyanamide concentrations and the inhibition of high-Km ALDH were established by means of the sigmoid Imax model. The effect of dosing rate on the plasma concentration of cyanamide at apparent steady-state showed non-linearity, indicating that clearance or first-pass metabolism of cyanamide during its absorption after intraperitoneal administration did not remain constant throughout the range of doses studied. PMID- 8218961 TI - The use of a nonlinear absorption model in the study of ascorbic acid bioavailability in man. AB - A two-compartment disposition model of ascorbic acid (AA) pharmacokinetics with saturable and time-constrained intestinal absorption was developed. The model was fitted to pharmacokinetic data obtained after oral administration to nine healthy volunteers of two effervescent dosage forms differing in AA content: Celaskon 60 mg (CK60) and Celaskon 500 mg (CK500). It was demonstrated that in the case of CK500 less than 30% of the dose was absorbed as compared with CK60. Parameters of the AA nonlinear absorption kinetics were assessed by simultaneous fitting of mean concentration-time data for both doses and placebo. The relatively short duration of absorption found (3.2 h) can explain the failure of past attempts to increase the AA bioavailability using sustained-release dosage forms. Model simulation showed that the ingestion of 60 mg with 3-4 h intervals is optimal for maximal bioavailability of AA. PMID- 8218962 TI - Toxicokinetic approach for evaluating respiratory depression effect of aminoglycoside antibiotics: species differences in drug susceptibility. AB - The respiratory depression effect of aminoglycoside antibiotics was studied by a toxicokinetic approach, and species differences in drug susceptibility were elucidated based on plasma concentrations. An allometric relationship was obtained between total body clearance of arbekacin, a novel aminoglycoside antibiotic, and animal body weight. The power was 0.714, less than unity, which means smaller animals have higher ability to eliminate the drug from the body and need higher doses to attain a certain steady-state plasma concentration. When the infusion rate of arbekacin was altered, the total dose required to cause the toxicologic endpoint for respiratory depression (60 per cent loss of respiratory rates) changed greatly, but the plasma concentration of arbekacin at the toxicologic endpoint remained at almost a constant level. The concentration at the toxicologic endpoint was similar for all of the animal species examined and was 650-950 micrograms ml-1, even though the total dose required to cause the toxicologic endpoint varied greatly among the animal species. These findings suggest that the toxicologic effect compartment for respiratory depression is indistinguishable from the plasma compartment, and that species differences in the total dose are due to differences in pharmacokinetics of the drug, mainly in the total body clearance, but not to differences in intrinsic susceptibility to the drug. PMID- 8218964 TI - Effects of water deprivation on the pharmacokinetics and pharmacodynamics of bumetanide in rats. AB - The effects of temporary water deprivation for 48 h on the pharmacokinetics and pharmacodynamics of bumetanide were examined after intravenous (i.v.) administration of bumetanide, 8 mg kg-1 to control and water deprived rats (n = 7). The values of AUC, t1/2 and MRT increased 79.0, 417, and 633 per cent, respectively, and CL and CLNR decreased 44.0 and 41.2 per cent, respectively, in water deprived rats. They were all significantly different. The decreased CLNR in water deprived rats could be due to decreased nonrenal metabolism of bumetanide; it could be supported that the amounts of glucuronide conjugate of bumetanide (52.5 vs 12.9 micrograms), desbutylbumetanide (170 vs 113 micrograms) and its glucuronide conjugation (191 vs 125 micrograms), and sum of the three metabolites (414 vs 229 micrograms), which are expressed in terms of bumetanide excreted in 24 h urine, decreased significantly in water deprived rats. The 8-h urine outputs per 100 g body weight (4.32 vs 1.34 ml) also reduced significantly in water deprived rats, and it might be due to significantly reduced amounts of bumetanide excreted in 8 h urine (90.9 vs 25.7 micrograms) and/or reduced kidney function in water deprived rats. The kidney function based on CLIot (9.87 vs 2.14 ml min-1 kg 1) reduced significantly in water deprived rats. The 8-h urinary excretions of sodium (0.430 vs 0.0818 mmol), potassium (0.567 vs 0.270 mmol), and chloride (0.549 vs 0.0624 mmol) per 100 g body weight also reduced significantly in water deprived rats. PMID- 8218963 TI - Relationship between lung tissue and blood plasma concentrations of inhaled budesonide. AB - In 11 patients, in whom a lung lobe or whole lung was to be resected, a single dose of 1.6 mg inhaled budesonide was given pre-operatively. In 9 of them, concentrations of the drug in both lung tissue and blood plasma were measured. Budesonide concentrations in lung tissue, at least 90 min after dosage, were 2.1 8.9 nmol kg-1. Concentrations in blood plasma (0.27-1.1 nmol kg-1) were 1/8th of those in lung tissue. PMID- 8218965 TI - Disposition of enantiomers of sulpiride in humans and rats. AB - Pharmacokinetics of sulpiride enantiomers after intravenous administration of (+/ )-, (+)-, and (-)-sulpiride was examined in humans and rats. Pharmacokinetics profiles were similar in (+)- and (-)-enantiomers after intravenous administration of (+/-)-sulpiride. Metabolic inversion at a chiral centre was not observed after intravenous administration of each enantiomer in rats. PMID- 8218966 TI - Bioavailability of intramuscularly administered tenoxicam. AB - Bioavailability of intramuscularly administered tenoxicam relative to single oral and relative to intravenous doses was determined in two separate randomized crossover studies. Twelve healthy volunteers (12 males, age 20-30 years) received a rapid intravenous injection and a single intramuscular dose and 12 other subjects (11 males, 1 female, age 21-25 years) a single oral and a single intramuscular dose of 20 mg of tenoxicam on two different occasions. The wash-out period between the two consecutive treatments was 4 weeks. Plasma concentrations after dosing were determined by a specific HPLC method. Differences in tenoxicam concentration-time profiles after the different routes of administration were limited to the first 2 h after dosing. Later, plasma concentrations were almost superimposable within and across the two studies. The extent of absorption of intramuscularly administered tenoxicam was complete (mean +/- CV per cent: F(abs) 0.99 +/- 20 per cent) with no difference between the two extravascular administrations (F(rel) 0.95 +/- 10 per cent, intramuscular vs oral). After intramuscular administration tenoxicam was more rapidly absorbed compared to the oral dose (Tmax 0.71 h +/- 80 per cent vs 1.4 h +/- 62 per cent; p > 0.05). Peak concentrations after oral and intramuscular administration (Cmax 2.5 mg l-1 +/- 19 per cent vs 2.7 mg l-1 +/- 14 per cent; p < 0.05) were very similar. PMID- 8218967 TI - Pharmacokinetics of naproxen, its metabolite O-desmethylnaproxen, and their acyl glucuronides in humans. AB - The aim of this investigation was to assess the pharmacokinetics of naproxen in 10 human subjects after an oral dose of 500 mg using a direct HPLC analysis of the acyl glucuronide conjugates of naproxen and its metabolite O desmethylnaproxen. The mean t1/2 of naproxen in 9 subjects was 24.7 +/- 6.4 h (range 16 to 36 h). The t1/2 of 7.4 as found in subject number 10 must, therefore, be regarded as an extraordinary case (p < 0.0153). Naproxen acyl glucuronide accounts for 50.8 +/- 7.32 per cent of the dose, its isomerized conjugate isoglucuronide for 6.5 +/- 2.0 per cent, O-desmethylnaproxen acyl glucuronide for 14.3 +/- 3.4 per cent, and its isoglucuronide for 5.5 +/- 1.3 per cent (n = 10; 100 h collection period). Naproxen and O-desmethylnaproxen are excreted in negligible amounts (< 1 per cent). Even though urine pH of the subjects was kept acid (range pH 5.0-5.5) in order to stabilize the acyl glucuronides, isomerization takes place in blood when the acyl glucuronide is released from the liver for excretion by the kidney. Binding to plasma proteins was measured as 98 per cent and 100 per cent, respectively for the unconjugated compounds naproxen and O-desmethylnaproxen. Binding of the acyl glucuronides was less, being 92 per cent; for naproxen acyl glucuronide, 66 per cent for naproxen isoglucuronide, 72 per cent for O-desmethylnaproxen acyl glucuronide and 42 per cent for O-desmethylnaproxen isoglucuronide. PMID- 8218968 TI - Bumetanide binding to normal albumins and to albumin in renal failure. AB - Binding of bumetanide, a loop diuretic, to partially purified albumins from renal failure patients (RF-HA), and healthy subjects (N-HA), human serum albumin (HSA) and defatted-HSA (D-HSA), was studied with equilibrium dialysis at a constant albumin concentration and various ligand concentrations. Binding parameters (n and K) were estimated from Scatchard plots and with a non-linear two-binding site model computer program, assuming two classes of independent sites. The binding capacities (n1K1) decreased in the order N-HA > RF-HA > D-HSA > HSA. Computer estimates of K1 for the partially purified albumin preparations were not markedly different. However, the graphical estimate of K1 for N-HA was greater than that for RF-HA. When the degree of binding (r) was plotted as a function of the logarithm of the free bumetanide concentration, an asymptotic plateau was not observed, indicating that the protein binding sites were not saturated. Consequently, the calculated binding estimates may not adequately describe the binding of bumetanide. PMID- 8218969 TI - Influence of food intake on the pharmacokinetics of a sustained release formulation of sodium valproate. AB - The effect of food intake on the pharmacokinetics of DEPAKINE CHRONO 500 mg (Sanofi, France), a sustained release formulation containing 333 mg sodium valproate and 145 mg valproic acid, was studied in 12 young healthy female volunteers. Relative to fasting conditions (F), when the tablet was given at the midpoint of the breakfast (NF), the maximum concentration (F: 34.6 +/- 8.9 micrograms ml-1 and NF: 40.9 +/- 7.3 micrograms ml-1; p = 0.014) and the mean cumulative amount absorbed up to time 6 h (F: 76.3 +/- 11.8% and NF: 90 +/- 10.4%; p = 0.0099) were significantly increased. Nevertheless, the extent of absorption (F: 46.7 +/- 9.9 mg l-1; NF: 48.7 +/- 7 mg l-1) was not significantly affected. There was no change in the area under the curve (1129 micrograms.h ml 1), in the mean residence time (28 h), or in the elimination half-life (16 h). On the basis of this study, the question as to whether DEPAKINE CHRONO should be administered to subjects in the fasting or non-fasting state would not appear to be a major consideration when deciding on the regimen. PMID- 8218970 TI - Metabolism and disposition of EXP631--a novel antidepressant analgesic. AB - EXP631, 4-(3-thienyl)-alpha, alpha,1-trimethyl-4-piperidine-methanol hemi fumarate salt (I), is a centrally acting non-opioid analgesic compound with monoamine uptake blocking properties. EXP631 has analgesic effects in several animal models. It is intended to be used for the treatment of moderate to moderately severe acute and chronic pain. To characterize the disposition of EXP631, the plasma levels of EXP631 were determined in rats and dogs after single intravenous and oral doses. In rats, EXP631 was rapidly absorbed following a single oral solution dose of 5-20 mg kg-1 with maximum plasma levels detected within 1.2 h post dose. The absorption was complete with an oral bioavailability of 92-131%. The pharmacokinetics was dose independent as measured by either Cmax or AUC values. In fasted dogs, EXP631 was absorbed rapidly and well (F = 81%) from an oral solution with the maximum concentration detected at 20 min post dose. In fed dogs, the absorption from capsules was slower (1.38 h) compared to the solution, but the absorption was complete (F = 115%). An N-desmethyl metabolite (II) was found in both rat and dog plasma samples. The structure was confirmed by mass spectroscopy, nuclear magnetic resonance spectroscopy and comparative chromatographic retention times. The metabolite is inactive as an analgesic. PMID- 8218971 TI - Pharmacokinetics and pharmacodynamics of bumetanide after intravenous and oral administration to spontaneously hypertensive rats and DOCA-salt induced hypertensive rats. AB - The pharmacokinetics and pharmacodynamics of bumetanide were investigated after intravenous (i.v.) administration, 10 mg kg-1, and oral administration, 20 mg kg 1, to spontaneously hypertensive rats (SHRs) and deoxycorticosterone acetate-salt induced hypertensive rats (DOCA-salt rats). After i.v. administration, the pharmacokinetic and pharmacodynamic parameters of bumetanide did not vary significantly between SHRs and the control Wistar rats. Similar results were also shown between DOCA-salt rats and the control Sprague-Dawley (SD) rats. After oral administration, the AUC0-12 h decreased significantly (186 versus 335 micrograms min ml-1) in SHRs and this resulted in decreased F(15.4 versus 23.6 and 2.78 versus 5.76% using two equations) in SHRs when compared with the control Wistar rats, although none of the other pharmacokinetic parameters varied significantly between SHRs and Wistar rats. This effect seemed to be due to the decreased enterohepatic recirculation of bumetanide in SHRs: the amounts of both bumetanide and its glucuronide product, which are capable of enterohepatic recirculation, excreted in 8 h bile juice decreased significantly in SHRs (11.3 versus 37.4 micrograms as expressed in terms of bumetanide) when compared with Wistar rats. The pharmacodynamic parameters did not vary significantly between SHRs and Wistar rats after oral administration of bumetanide. The pharmacokinetic and pharmacodynamic parameters of bumetanide did not vary significantly between DOCA salt rats and SD rats after oral administration of the drug. The liver weights compared to body weight increased significantly in SHRs when compared with Wistar rats and the corresponding values for the kidney increased significantly in DOCA salt rats when compared with SD rats. PMID- 8218972 TI - Influence of the diet on bioavailability of tetracycline. PMID- 8218973 TI - Overview of quantitative methods in toxicologic pathology. AB - Today's stringent requirements for new drugs make it necessary to prove their safety by the use of ever more refined techniques, in particular methods to quantify morphologic findings to determine accurately, for example, the highest non-toxic dose in animal studies or to correlate morphological effects with other parameters. Increased cell proliferation due to subtle cytotoxicity can lead to epigenetic tumorigenicity, which can be recognized early by cytokinetic investigations using bromodeoxyuridine (BrdU) incorporation and/or proliferating cell nuclear antigen (PCNA) expression, or by malignancy-associated nuclear texture changes. Morphometric criteria are also used to increase diagnostic accuracy in experimental animal pathology. The various applications of morphometry in toxicopathology are reviewed, and examples illustrating these applications are presented, most of them unpublished. PMID- 8218974 TI - Toxic effects in rats of twelve weeks' dosing of 2-propanol, and neurotoxicity measured by densitometric measurements of glial fibrillary acidic protein in the dorsal hippocampus. AB - The toxicological and neurotoxicological effects of 2-propanol were investigated in a 12-week study in male rats. 2-propanol was administered in drinking water in concentrations of 0, 1, 2, 3 and 5% (w/v). Autopsy and histopathological examinations of liver, heart, spleen, testes, kidneys and adrenals were performed. The content of glial fibrillary acidic protein (GFAP) was measured semiquantitatively by a densitometric method applied to immunohistochemically stained sections from the dorsal hippocampus. The relative organ weights of liver, kidneys and adrenals were statistically significantly increased in a dose dependent manner. No histopathological alterations could be attributed to the dosing, apart from a dose-dependent increase in formation of hyaline casts and droplets in the proximal tubules of the kidneys. 2-propanol does not seem to cause astrogliosis after 12 weeks of dosing. PMID- 8218975 TI - Progress in telepathology. AB - The basic principles, technical objectives and future aspects of telecommunication in pathology (telepathology) are discussed. Visual information, which is the usually the basic source of medical disease classification, and its transfer have to be distinguished from acoustic information, which is commonly of secondary, i.e. abstract nature. Visual telecommunication in pathology can be applied in five different aspects, namely: a) to create visual data bases, b) to be used in expert consultation, c) to combine morphological and clinical data, d) to quantitate morphological findings (DNA- measurements, etc.), and e) to install remote control microscopes. Depending upon the application, different technical prerequisites and constraints have to be taken into account: queries of visual data bases and expert consultations can be performed by use of "normal" telephone lines; combination of morphological and clinical data and quantitation of morphological data may need a digitized telephone network (ISDN), and the transfer of live images needed for application of remote control microscopes can only be performed by use of ISDN or broadband networks (optical fiber transmission systems, satellite communication, etc.). The experiences of various groups working in different aspects of telepathology are described. PMID- 8218976 TI - Assessment of infarct volume in the mouse brain: correlation of magnetic resonance imaging with morphometry. AB - In the mouse brain, focal necrotic lesion was induced by occlusion of the left middle cerebral artery. The volume of cerebral edema was quantified two days later by MRI in vivo. Histological examination after 2 to 3 months of survival revealed a loss of tissue in the affected brain hemisphere predominantly involving the cortex. The extent of brain atrophy as determined by morphometry correlated well with the volume of edema as measured by MRI. There was a cerebroprotective effect of the N-methyl-D-aspartate receptor antagonist MK 801 on the extent of brain damage as determined by both analytical methods. PMID- 8218977 TI - Nuclear texture during the cell cycle in acute lymphoid leukemia. AB - Description of morphological and textural changes during cell cycle were studied in 31 diploid Acute Lymphoid Leukemia ALL cases. Feulgen stained nuclei were measured by image analysis. Cells with 2C, 3C and 4C content of DNA were considered as being in G1, S and G2 phase of cell cycle respectively. The main observed transformations associated with cell cycle were continuous increases in nuclear size and in quantities of black/white chromatin clumps and points. An overall correct classification of 92.5% was achieved by multivariate data analysis. However, significant differences between A L L cases were noticed. PMID- 8218978 TI - Flow cytometrical considerations. The results of three different ways of nuclear preparation and two ways of calculating upon DNA index, number of populations and S-phase rate in endometrial tissue. AB - Histopathologically normal endometrial tissues were used to compare the preparation methods of Tribukait, Thornthwaite and Vindelov. Three hundred and forty-one preparations were analyzed giving as a result significant differences regarding the DNA-indices, number of DNA-populations and percentage of cells in S phase fraction. We also compared a manual way of calculation to a semi-automatic method (RFIT). No difference was found between the manual way and RFIT provided that the same internal standard was used. However, the two different internal standards gave different results within the same method of preparation. PMID- 8218979 TI - Effect of preoperative training on latissimus dorsi muscle for cardiomyoplasty. A morphometric study. AB - Dynamic cardiomyoplasty is based upon the use of electrostimulated Latissimus Dorsi muscle (LDM) to reinforce the ventricular wall of heart in patients with end-stage heart failure. In the present study we induced a preoperative reinforcement of LDM in 3 male patients selected for cardiomyoplasty, by means of a physiokinesiologic training. The application of morphometric techniques was useful to analyze the modifications in fibre type diameter and composition, in number and distribution of mitochondria and in number of capillaries in LDM needle biopsies performed before and after training. The preoperative muscle training induces trophic modifications in muscle fibres with increase in fibre diameter, in capillarity and in number and size of mitochondria. These parameters indicate that a preoperative training of LDM before cardiomyoplasty may be useful for muscle reinforcement and for preparation to the electrostimulation program in the postoperative cardiac assistance. PMID- 8218980 TI - DNA ploidy in undifferentiated carcinomas of the human stomach-with special reference to its heterogeneity and the relation between its intratumor distribution pattern and prognosis. AB - The intratumor DNA ploidy distribution pattern in 74 undifferentiated carcinomas of the human stomach was analysed by flow cytometric measurements of DNA for stepsectioned specimens taken from throughout the entire tumor. 52 cases showed intratumor DNA ploidy heterogeneity (70.3%), and a conspicuous difference between intramural and transmural carcinomas was seen with regard to the intratumor DNA ploidy distribution pattern as well as prognosis. In the case of transmural carcinomas, the following findings were noted: prognosis was significantly worse, predominant aneuploidy was seen more frequently, the frequency of intratumor DNA ploidy heterogeneity as well as DNA content was significantly increased, and predominant diploidy exhibited a worse prognosis. These were all in contrast to the findings for intramural carcinomas. PMID- 8218981 TI - A new expert system for histopathological diagnosis of human ovarian epithelial cancer. AB - A new rule-based expert system designed to assist pathologists in the histological diagnosis of human ovarian epithelial cancer has been developed. The system was implemented using the INSIGHT II+ EXPERT System Shell and runs on IBM compatible microcomputers. It operates using knowledge acquired through the literature, research and experience, formulated into a total of 195 IF-THEN rules. The WHO International Histological Classification of Tumours is being used throughout. The system can quickly focus on a differential problem, thereby reducing the time necessary to reach a conclusion. It has been tested on a set of 34 cases, previously examined by pathologists of the Metaxas Memorial Cancer Institute, and has been found to reach good agreement with the pathologists' diagnoses. PMID- 8218982 TI - Information retrieval for pathology information systems. AB - In a medical information system there is a serious need for assessing patient information in various ways. There is also a need for summarizing information in simple statistical tabular form. In this part we present and evaluate different techniques for query formulation, such as: QBE (Query-by-Example), SQL (Structured Query Language), GCL (Graphical Query Language). We also present a query processor for use in a pathology information system. This software system incorporates: a) A semi graphical tree structure interface (SGTSI) for query formulation, and b) Summary tables handling. PMID- 8218983 TI - Diagnostic decision support by inference networks. AB - Inference networks permit the combining of diagnostic evidence in such a fashion that the mutual dependence structure of different pieces of evidence is considered, and that a probabilistic measure of the uncertainty of the final diagnostic decision is provided. Operated in an automatic reasoning mode, an inference network allows a decoupling of the false negative rate from the false positive rate in diagnostic procedures involving rare event detection such as the prescreening for cervical cancer. PMID- 8218984 TI - Integrated optical density and entropiefluss (current of entropy) in bronchial carcinoma. AB - Histological sections of formalin-fixed, paraffin-embedded bronchial carcinomas comprising 241 surgical specimens (lobes and lungs) were Feulgen stained. The integrated optical density of the nuclei (IOD) and the minimum distance between their centers of gravity (DG) was measured with an automated image analyzing system consisting of a TV camera connected to a personal computer via a frame grapper. Intratumorous lymphocytes served as DNA standard (2C peak), and 300 nuclei were measured at minimum. The entropy of the IOD, the percentage of S phases (PS) of tumor cells with an IOD > 3C and > 5C, and the 2CV mean standard deviation were measured. According the theory of thermodynamically open systems, the entropiefluss (current of entropy) was defined by the gradient IOD/time through the surface of the tumors which can be approximated by the formula IOD*PS*DG/tumor volume. The following results were obtained: a) IOD of bronchial carcinoma is not associated with tumor size or lymph node infiltration (pT and pN stage). b) The minimum distance between tumor cells decreases with increasing tumor stage and increasing lymph node stage (pT, pN stage). c) The entropiefluss is low in limited and advanced tumor stages, and highest in tumors at moderately progressive tumor stages (pT2, pT3, pN1, pN2). Thus, in accordance with the theory of thermodynamically open systems, the entropiefluss reflects the "biological activity" of bronchial carcinoma. PMID- 8218985 TI - Quantitative approach to the immunohistochemical analysis of p53 antioncogene and CD30 antigen in Hodgkin' disease. AB - In this paper a multimarker immunohistochemical technique is described in detail which allows the quantitative evaluation in situ of cells expressing abnormal accumulation of p53 phosphoprotein together with the CD30 antigen, a well known marker of Hodgkin's and Reed-Sternberg cells. The method is useful to define quantitatively the proportion of phenotypically abnormal cells in the complex microenvironment of Hodgkin's lesions, and to compare the phenotypical derangement of p53 gene with molecular biology data obtained on the same samples. PMID- 8218986 TI - Aids of telepathology in intra-operative histomorphological tumor diagnosis and classification. AB - Visual telecommunication (telepathology) was applied for expert consultation in intra-operative frozen sections and tumor classification of paraffin-embedded, poorly differentiated bronchial carcinoma. The Institute of Pathology, Hospital Baumgartnerhohe, Vienna and the Department of Pathology, Thoraxklinik, Heidelberg transmitted histological images by use of commercially available computerized modems (VP 2000) and conventional telephone lines. The expert consultation of the frozen sections included the clinical history, macroscopic findings and problems of final judgement of the images. Additional useful information could be obtained in about 35% of cases, and comprised expansion of differential diagnosis, certainty of final diagnosis, and side findings, such as concurrent inflammation, sarcoid-like lesions, etc. The time required for intra-operative diagnosis was 6 10 min. Cases of the Austrian-German quality control study on lung cancer with divergent tumor classification were discussed by use of telepathology. A final congruent tumor diagnosis could be obtained in all divergent cases. The data indicate that telepathology can be successfully used for expert consultation of intra-operative frozen sections and panel discussions of difficult bronchial carcinoma cases. PMID- 8218987 TI - Induced gall-bladder contraction accelerates fragment clearance after extracorporeal shockwave lithotripsy. AB - At the end of extracorporeal shockwave lithotripsy (ESWL) gallstone fragments are dispersed throughout the gall-bladder. In this state they should be expelled more easily than when later sedimented to the gall-bladder fundus. Thus, a randomized study was performed to evaluate the clinical benefit of induced gall-bladder contraction after ESWL. One hundred and five patients with radiolucent gallstones (1-3 stones, diameter < or = 30 mm) were randomized to received either saline or an infusion of 0.2 micrograms/kg ceruletide. Stone clearance rates and incidence of biliary symptoms were recorded. Clearance rates at 6 weeks and 3 months after ESWL were significantly (P < 0.025) improved by the ceruletide infusion. This effect, resulting in shortened bile acid therapy, was limited to patients with small solitary stones and dependent on a good initial fragmentation. Major side effects attributable to ceruletide were not observed. These results suggest that induced gall-bladder contraction can be successfully applied as an adjuvant treatment in a subgroup of patients with small solitary gallstones. PMID- 8218988 TI - Changing prevalence of hepatitis B virus in urbanized Australian aborigines. AB - Serological surveys of desert or rural Australian Aboriginal settlements report up to 85% positivity for hepatitis B virus (HBV) markers. We report the results of two cross-sectional HBV surveys carried out 5 years apart in the bi-racial town of Condobolin, New South Wales (population 3086; 14% Aborigines). In 1983 84, none of the 310 non-Aborigines tested were hepatitis B surface antigen (HBsAg) positive but 7.2% were positive for hepatitis B core antibody (anti-HBc). Among Aboriginal subjects, 57.6% had detectable HBV markers and 16.9% were HBsAg positive. In 1987-88, no non-Aborigines were HBsAg positive and only 1% (of 422 individuals) had anti-core antibodies. In contrast, 36% of Aboriginal subjects had HBV markers and 6% were HBsAg positive. No significant difference in detectable HBV markers was found among 98 Aborigines who were included in both surveys. Migration was the main factor influencing the HBV prevalence between the two surveys. Clustering of HBsAg carriers occurred within households and the likely mode of infection was intrafamilial horizontal childhood transmission. There was a significant association between HBV markers and tattooing in Aborigines (P < 0.02). Overall, HBV markers were less frequent in this population than in other desert or rural Aboriginal populations surveyed. The prevalence of HBV infection in non-Aboriginal households was not significantly different from that in the Australian Caucasian population. PMID- 8218989 TI - Trimethadione tolerance tests for the assessment of feasible size of hepatic resection in patients with hepatocellular carcinoma. AB - Pre-operative evaluation of the quantity of functional remnant hepatic parenchyma after hepatectomy was carried out to predict the optimal amount of hepatic resection using the trimethadione (TMO) tolerance test. This test is an estimate based on serum diamethadione (DMO)/TMO ratio (DMO is the only metabolite of TMO) 4 h after oral administration of TMO, and computed tomography (CT) scans of the liver in patients with hepatocellular carcinoma (HCC). The percentage of remnant hepatic parenchyma was calculated pre-operatively from the remaining non cancerous portion and the whole hepatic parenchyma, excluding the HCC portion, using the CT scans. Presumptive remnant DMO/TMO ratio was calculated by multiplying the percentage of remnant hepatic parenchyma and pre-operative serum DMO/TMO ratio in 45 patients with HCC undergoing resection. The presumptive remnant DMO/TMO ratios were 0.31 +/- 0.10 (mean +/- s.d.) in 42 patients who survived hepatectomy and 0.13 +/- 0.02 (below 0.15) in the three patients who died from postoperative hepatic failure. Of these surviving patients, two patients who had the presumptive remnant DMO/TMO ratios under 0.15 developed postoperative severe complications. Thus, hepatectomy may not be indicated in patients where presumptive remnant DMO/TMO ratio is 0.15 and lower. These findings suggest that pre-operative measurement of presumptive remnant DMO/TMO ratio, when obtained with the CT of the liver and TMO tolerance test, is useful for prediction of the quantity of functional remnant hepatic parenchyma after hepatectomy in patients with chronic liver disease. PMID- 8218990 TI - Risk of liver cirrhosis and hepatocellular carcinoma in subjects with hepatitis B and delta virus infection: a study from Kure, Japan. AB - To investigate the effect of hepatitis delta virus (HDV) superinfection on the long-term outcome of Japanese subjects with chronic hepatitis B virus (HBV) infection, we examined the presence of antibodies to hepatitis delta antigen (anti-HD) in serial serum samples collected from 1127 subjects with chronic HBV infection. The subjects were followed for at least 36 months (mean: 121.3 months) between 1973 and 1991. Among 69 cases where anti-HD was detected, eight (12%) developed liver cirrhosis (LC) and six (9%) developed hepatocellular carcinoma (HCC). However, among 1058 cases without anti-HD, there were 43 patients (4%) who developed LC and 29 (3%) who developed HCC. The prevalence of LC and HCC was significantly higher among the cases with anti-HD than those without anti-HD. The proportion of LC and HCC per 1000 person years was 10.46 and 7.84, respectively among cases with anti-HD, and 4.05 and 2.73 among those without anti-HD, respectively. The overall relative risk of LC and HCC was 2.58 and 2.87, respectively; 95% confidence interval (CI): LC, 1.14-5.13; HCC, 1.03-6.23. These results indicate that in the Kure district in Japan, where HDV infection of persons infected with HBV is about 6%, such superinfection increases the risk of LC and HCC. PMID- 8218991 TI - Clinical evaluation of serum tissue inhibitor of metalloproteinases-1 levels in patients with liver diseases. AB - Serum levels of the tissue inhibitor of metalloproteinases-1 (TIMP-1) were measured in 268 patients with liver diseases by means of a one-step sandwich enzyme immunoassay. In the cases of acute hepatitis, chronic active hepatitis (CAH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC), the levels of TIMP-1 were higher than those of the control group. Tissue inhibitor of metalloproteinases-1 levels correlated with type III procollagen peptide and with type IV collagen, indicating TIMP-1 as a useful marker for hepatic fibrosis. Levels of TIMP-1 also correlated with aspartate aminotransferase and alanine aminotransferase levels and showed the highest levels in acute hepatitis. Thus, TIMP-1 might also reflect hepatic inflammation. Serum levels of alpha-fetoprotein and TIMP-1 had a significant positive correlation in patients with HCC. A cut-off level of TIMP-1 between LC and HCC was set at 440 ng/mL, having a low sensitivity and a high specificity. These results suggest the usefulness of TIMP-1 as a tumour marker in cases of HCC where alpha-fetoprotein levels are not elevated. PMID- 8218992 TI - Elevated growth hormone levels in patients with non-alcoholic chronic liver disease. AB - High serum concentrations of growth hormone (GH) were found in five patients with chronic liver diseases, including auto-immune chronic active hepatitis (two cases), Budd-Chiari syndrome, primary biliary cirrhosis and hepatitis B virus associated cirrhosis. Mean levels of GH were 27.8 units (normal up to 5). In three patients elevated prolactin levels were also found (mean 37.3 units for two females, normal up to 20), and 36 units in one male (normal up to 9). No other endocrine disorders were found. Although the association of raised GH levels in patients with alcoholic cirrhosis is well known, its occurrence in patients with non-alcoholic chronic liver disease is not fully established. We describe the effect of the disease course, and steroid treatment on GH levels in one patient with auto-immune chronic active hepatitis, and propose possible mechanisms for this elevation. PMID- 8218993 TI - Ultrastructural filament organization of hepatocyte cytoplasm revealed by embedment-free sections of rat liver. AB - The cytoplasmic matrix of rat liver cells was examined by embedment-free electron microscopy of polyethylene glycol (PEG) embedded tissue from which the PEG had been removed subsequently. Non-ionic detergent extraction of fresh blocks of tissue permitted the major cytoskeletal components to be visualized in relatively thick embedment-free sections. Immunolabelling confirmed the presence of the major cytoskeletal proteins (actin, cytokeratin and tubulin) in these sections. Hence, this method permits the examination of the ultrastructural organization of the cytoskeleton of the hepatocyte in blocks of fresh hepatic tissue. PMID- 8218994 TI - Role of superoxide dismutase in mechanism of diethyldithiocarbamate-induced gastric antral ulcer in rats: protective effect of prostaglandin, cimetidine and pirenzepine. AB - The role of superoxide radicals and the protective effects of superoxide dismutase (SOD), allopurinol, 16,16-dimethyl-prostaglandin E2 (dmPGE2), cimetidine and pirenzepine in diethyldithiocarbamate (DDC)-treated rats were evaluated. Pretreatment with Cu,Zn-SOD (superoxide radical scavenger) 60,000 units/kg, allopurinol (competitive inhibitor of xanthine oxidase) 50 mg/kg, dmPGE2 (prostaglandin analogue) 10 micrograms/kg, cimetidine (H2-receptor antagonist) 10 mg/kg or pirenzepine (selective antimuscarinic drug) 10 mg/kg all significantly reduced the DDC-induced (800 mg/kg) gastric antral ulcer formation in rats. DDC treatment substantially decreases the gastric mucosal Cu,Zn-SOD activity. In this study treatment with DDC and SOD, DDC and dmPGE2, DDC and cimetidine, and DDC and pirenzepine were demonstrated significantly to prevent the decrease of gastric mucosal Cu,Zn-SOD activity. However, allopurinol did not have this effect. The results suggest that SOD and/or superoxide radicals may play an important role in the mechanism of DDC-induced gastric antral ulcer. The protective property against ulcer formation of these drugs studied might be due to the action of SOD in the gastric mucosa. PMID- 8218995 TI - Crohn's disease in children from the western region of Saudi Arabia. AB - In this paper, we describe 17 children with Crohn's disease seen at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, who were followed up during a period of 10 years (1980-90). Their ages ranged from 5 to 15 years. The average duration of symptoms prior to presentation was 25 months (ranging from 4 days to 4 years). In this article, we describe the clinical picture, laboratory investigations and results, as well as the treatment of the affected children. PMID- 8218996 TI - Immunohistochemical demonstration of the p53 tumour suppressor gene product in cancer of the pancreas and chronic pancreatitis. AB - The p53 tumour suppressor gene and its protein products after point mutations are currently attracting wide attention in the investigation of human tumours. In this study we present the findings on percutaneous pancreatic biopsies of 82 cases after routine processing and immunostaining for the polyclonal p53 antibody CM1, an antibody directed against both wild and mutant forms of p53 protein. There were 51 carcinomas, 5 islet cell tumours, 16 cases of chronic pancreatitis (including one with atypical ductal epithelium) and seven histologically normal pancreatic biopsy specimens. None of the seven normal cases showed any definite nuclear immunostaining for p53. Thirty-two (63%) of the pancreatic adenocarcinomas showed moderate to intense immunoreactivity. Of the 16 cases of chronic pancreatitis, 11 were negative and three showed equivocal immunostaining. The one case with ductal epithelial atypia showed mild to moderate immunoreactivity. All islet cell tumours were negative. The expression of the p53 gene, therefore, appears increased in the majority of pancreatic adenocarcinomas while this is not observed in chronic pancreatitis or normal pancreatic tissue. Nuclear immunoreactivity for p53 protein may represent mutant forms because of the short half-life of the wild-type protein. The lack of p53 expression in some cases of pancreatic adenocarcinoma may be due to different types of mutant proteins not detectable by the CM1 antibody. Nuclear immunoreactivity to the p53 protein in pancreatic biopsy is more suggestive of a malignant tumour than chronic pancreatitis. PMID- 8218997 TI - Natural history of chronic hepatitis B virus infection: new light on an old story. AB - Chronic hepatitis B virus (HBV) infection is one of the most common persistent virus infection in man. It causes significant morbidity and mortality, and therefore is important. Extensive studies on clinicopathologic studies and long term follow up on hepatitis B surface antigen (HBsAg) carriers have largely disclosed the natural history of chronic HBV infection. The infection easily becomes chronic when contracted in early infancy. As high as 90% of babies born to HBV carrier mothers will also become HBsAg carriers. Once chronic infection is established, it is refractory, and HBsAg carriage usually persists for life. However, the chronic infection is not monotonous, it actually evolves from an HBV replicative phase to a non-replicative phase. The host responds differently and with more complexity in different phases. The virus-host interactions, divided into three phases, virus tolerance, virus clearance and residual HBV integrated phases, result in a heterogeneous variety of hepatic lesions. The first two phases occur when HBV is actively replicating, and the last corresponds to the non-replicative phase. The high HBV level (and hence HBV gene products) renders the host's immune system tolerant to the virus, and the infected host does not exert an effort to get rid of the virus. At this stage, the liver is nearly normal, and the host is asymptomatic. However, later in the replicative phase, the HBV replication begins to wane, and the immune tolerance is no longer maintained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8218998 TI - Peritoneoscopic cholecystectomy has opened the door to minimally invasive surgery. AB - In 1989 a new trend occurred in the surgical treatment of a diseased gall bladder, laparoscopic cholecystectomy (LC). Laparoscopic surgery is now accepted world-wide as the choice of treatment with the advantages of less pain, good cosmesis, short hospital stay and early recovery. It is also a curative procedure for cholelithiasis as well as a cholecystectomy. The rate of conversion to open surgery is about 5% and the rates of bile duct injury are 0.1-0.6%. This new approach revives controversies concerning cholecystectomy; namely indication, use of intra-operative cholangiography, ductal calculi and pregnancy. There are new issues to consider, including use of a Veress needle for pneumoperitoneum, type of trocars, cardiovascular responses to pneumoperitoneum using carbon dioxide and so on. With increasing use, these difficulties will be overcome. Advances in technology are expected to make even more new types of surgery possible, even perhaps extending into robotic surgery. PMID- 8218999 TI - Hepatic angiomyolipoma pre-operatively diagnosed by imaging. AB - An asymptomatic patient with pre-operatively diagnosed solitary angiomyolipoma is reported. The tumour was a well defined, fat density mass on computerized tomography (CT) and magnetic resonance imaging (MRI), and a hyperechoic nodule with a sharp margin on ultrasonography (US). The lesion was hypervascular on arteriography and CT during hepatic angiography. Chemical shift MRI confirmed the fat component within the lesion. Although a review of the literature shows this tumour to be rare and difficult to differentiate from a malignant lesion pre operatively, the pre-operative diagnosis of angiomyolipoma is considered feasible when the characteristic findings as described here are present. PMID- 8219000 TI - Marked retention of indocyanine green and sulfobromophthalein with chronic persistent hepatitis. AB - A hepatitis B virus (HBV) carrier with marked retention of indocyanine green (ICG) and sulfobromophthalein (BSP) was admitted to our hospital for assessment of liver function. On admission, he was asymptomatic and blood chemistry tests showed normal values for transaminases and bilirubin. Serum hepatitis B surface antigen (HBsAg) and antibody to hepatitis B e antigen (anti-HBe) were positive. A history of drug abuse or alcoholism was denied. Dye excretion tests revealed marked retention of ICG (R15 = 70%) and BSP (R45 = 23%). Histopathological examination of a liver biopsy specimen obtained during laparoscopic observation showed chronic persistent hepatitis (CPH). Familial research of the patient failed to prove the existence of dye excretory defect in his siblings. Usual cases of CPH due to continuous HBV infection do not show such severe disturbance of organic anion transport. This pattern of the dye excretory defect with CPH has not been reported. Although the relationship between this dye excretory defect and HBV infection is unclear, the existence of the constitutional dye excretory defect due to abnormal organic anion transport in the liver might be considered. PMID- 8219001 TI - Small angiomyolipoma of the liver diagnosed by fine-needle aspiration biopsy under ultrasound guidance. AB - The first reported case of small hepatic angiomyolipoma to be diagnosed by fine needle aspiration biopsy (FNAB) is described. A 53 year old man presented with a tumour in segment VI of the liver measuring 0.9 x 0.8 cm. The tumour was hyperechoic on ultrasound examination, showed relatively low density (+ 33 Hounsfield units) on computed tomography (CT), and was hypervascular on angiography. Computed tomography during arterial portography demonstrated a perfusion defect. Magnetic resonance imaging (MRI) revealed high intensity by both T1- and T2-weighted imaging. Diagnosis could not be obtained by these imaging modalities, but it was established successfully by FNAB under ultrasound guidance. Histologically, the tumour was an angiomyolipoma made up of three components: blood vessels, smooth muscle and fatty tissue. Surgery is unnecessary for this benign condition, and the patient has been followed up. Ten months later, the patient is currently doing well without growth of the hepatic angiomyolipoma. PMID- 8219002 TI - Review: on the chemistry of oxidative stress. AB - Injury of plant cells as well as mammalian cells is connected with the activation of 'dormant' lipoxygenases. In the presence of oxygen, these enzymes are activated and enabled to catalyze the formation of hydroperoxides of linoleic and other polyunsaturated fatty acids. Reactivity of dormant lipoxygenases seems to be dependent on the carbon number between the alkyl end and the double bond situated next to this end in an unsaturated acid. In contrast to these dormant lipoxygenases there exists a second group of lipoxygenases, which are active in plant cells all the time, independent of an injury. They react mainly with acids possessing two homoconjugated double bonds within a distance of seven CH2 groups from the carboxylic end. Thus, they 'count' from the reverse end of the molecule. These lipoxygenases produce F-acids. They are converted, when plant cells are injured by hydroperoxides produced from unsaturated acids, into dioxoenoic acid intermediates which probably are used for defense. In mammalian tissues, lipoxygenases produce in the case of cell injury plasmalogen epoxides. These are analogous to dioxoenoic acids' highly reactive intermediates (in a chemical sense) which react immediately with nucleophiles. Such transformation of plasmalogens may be responsible for the development of chronic diseases, e.g., atherosclerosis, Alzheimer's disease and also for aging. PMID- 8219003 TI - Platelet-activating factor (PAF)-induced cardiopulmonary dysfunctions and their reversal with a PAF antagonist (BN 52021) in strain 13 guinea pigs. AB - Cardiovascular and respiratory responses to a 2 h intravenous constant infusion of PAF (5 and 10 ng/kg per min) were studied in strain 13 guinea pigs. PAF decreased arterial blood pressure, left systolic ventricular pressure, and cardiac output (CO). These cardiovascular changes were dose-dependent. The PAF induced hypotension returned to a pre-infusion level spontaneously with increased total peripheral resistance despite continuous infusion of PAF. The decreased CO was most striking, and did not recover to pre-infusion levels due to depressed cardiac contractility and impaired ventricular relaxation. Respiratory responses to PAF infusion at these doses were mild and only occurred after serious cardiovascular dysfunctions developed. A higher dose of PAF (20 ng/kg per min) produced drastically decreased CO and dynamic lung compliance (Cdyn), increased pulmonary airway resistance, hypoventilation and apnea within 10-40 min. BN 52021, a PAF receptor antagonist, administered as a single i.v. dose (6 mg/kg) 15 min after PAF infusion, reversed most of cardiopulmonary dysfunctions and prevented death by increasing cardiac contractility, CO, and minute volume from extremely low values. The data suggest that marked cardiopulmonary disturbances induced by intravenous PAF infusion reflects certain pathophysiological mechanisms of diseases that may involve the cellular release of PAF. The administration of BN 52021 or other potent PAF antagonists may be beneficial under these circumstances. PMID- 8219004 TI - Transient temporal relationship between 1-oleoyl-2-acetyl-sn-glycerol (OAG) activated synthesis and hydrolysis of polyphosphoinositides: desensitization of phospholipase C and the inositol lipid kinases upon long-term treatment of ascites cells by exogenous OAG. AB - In ascites tumor cells, phosphoinositide metabolism can be activated by short term treatment with exogenously added 1-oleoyl-2-acetyl-sn-glycerol (OAG), which is the membrane-permeable analog of diacylglycerides (DAG). Quiescent cells prelabeled with D-myo-2-[3H]inositol and then stimulated with OAG (20 micrograms/ml of medium) reveal transient increases in the liberation of inositol 1,4-bis- and inositol 1,4,5-trisphosphate with peaks at 30 min, and a sustained accumulation of inositol phosphate 30 min after stimulation. The labeling patterns of the corresponding inositol lipids show transient activity profiles for phosphatidylinositol 4-phosphate (PtdIns(4)P) and phosphatidylinositol 4,5 bisphosphate (PtdIns(4,5)P2), and a sustained high activity level for PtdIns 30 min after OAG treatment. These data demonstrate a temporal relationship between synthesis and phospholipase C (PLC)-induced hydrolysis of these lipids. Simultaneous labeling of the cellular inositol phospholipids with [1 14C]arachidonic acid reveals modest accumulations after OAG stimulation. The relative 3H radioactivity distribution between the lipids and their inositol metabolites show that about 10% of the polyphosphoinositide pools are metabolically active. Long-term culturing of the cells (> 24 h) under OAG supplementation produces significant reductions in the catalytic activities of PLC and the PtdIns and PtdIns(4)P-specific kinases which is paralleled by a reduced radioactive labeling of PtdIns(4)P and PtdIns(4,5)P2 under these conditions. These data suggest that diglycerides affect the phosphoinositide metabolism by controlling PLC and phosphoinositide kinase activities probably via modification of membrane properties, and by functioning as modulator of other events. PMID- 8219005 TI - Cloricromene inhibits G-protein-mediated activation of phospholipase A2 in human platelets. AB - The coumarin derivative, cloricromene, an antithrombotic drug previously indicated as AD6, is known to inhibit the release of radioactive arachidonic acid from human platelets prelabelled with arachidonic acid and stimulated with thrombin. This effect might be due to the drug itself or to its catabolite, cloricromene acid. When added to platelet lysates neither compound inhibited phospholipase A2 activity assayed either with endogenous or with exogenous substrates. However, some inhibition was instead shown when intact platelets were first exposed to cloricromene and then enzyme activity was assayed in the lysate. Preincubation of platelets with the drug caused a dose-dependent inhibition of arachidonic acid mobilization in fluoroaluminate-stimulated platelets. beta Thromboglobulin (beta-TG) release, a phenomenon previously shown to share common steps with phospholipase A2 activation, was also dose-dependently inhibited by cloricromene. Cloricromene also reduced the radioactivity associated with phosphatidic acid in fluoroaluminate-stimulated platelets but not in platelets stimulated with thrombin. These results are consistent with the hypothesis that cloricromene, or its catabolite, inhibits the production of arachidonic acid in stimulated platelets by interfering with a G-protein mediated activation of phospholipase A2 that is independent from the receptor-activated phosphoinositide phospholipase C. PMID- 8219006 TI - The effect of heparin and related proteoglycans on allergen and PAF-induced eosinophil infiltration. AB - Exposure of normal guinea pigs to an aerosol of PAF induced a selective increase in the percentage of eosinophils in bronchoalveolar lavage (BAL) fluid 24 h after challenge. Challenge of actively sensitised guinea pigs with an aerosol of ovalbumin also induced a selective increase in the percentage of eosinophils recovered in BAL fluid 24 h post challenge. Pretreatment of actively sensitised guinea pigs or normal guinea pigs with unfractionated heparin significantly reduced such eosinophil infiltration induced by allergen or PAF challenge respectively, although higher amounts of heparin were required to inhibit antigen induced eosinophil infiltration. Similar effects were also observed following treatment with the low molecular weight heparin-like material ORG 10172 but not the anionic molecule polyglutamic acid or high molecular weight dextrans. These results suggest that proteoglycans may possess anti-allergic activity that is not necessarily related to either such molecules being anionic in nature nor to anti coagulant activity. PMID- 8219008 TI - A role of ADF chemosensory neurones in dauer formation behaviour in C. elegans. AB - In Caenorhabditis elegans, mutants in osmotic avoidance behaviour (osm), which fail to avoid high concentrations of salts and sugars, have been previously identified. These osm mutants are also defective in dauer larva formation, and fail to take up fluorescein dye in six pairs of amphid neurones (ADF, ADL, ASH, ASI, ASJ, and ASK) and two pairs of phasmid neurones. Analysis of the FITC dye uptake by osm-3 mutants show that seven of the eight osm-3 alleles can take up FITC dyes in one pair of amphid neurones, ADF. Comparison of dauer larva formation behaviour in different osm-3 alleles shows a direct correlation between improved behaviour and FITC dye uptake. Therefore, these allelic strains are useful in defining the role of ADF neurones in dauer larva formation. PMID- 8219007 TI - Autoradiographic study on [3H]-[D-Ala2]-deltorphin-I binding sites in the rat brain. AB - Previous biochemical and pharmacological studies have shown that [D-Ala2] deltorphin-I (DADTI) has a high affinity and selectivity for delta-opioid receptors. In this study, designed to provide morphological details, the distribution of DADTI binding sites was examined by autoradiography on coronal, sagittal and horizontal frozen sections of adult rat brain. The sections were incubated with tritiated DADTI solution and exposed for 12 weeks to a 3H sensitive film. DADTI labelling clearly demonstrated selective and high affinity binding sites of delta-opioid type in several brain regions, including olfactory system, neostriatum, nucleus accumbens, and cortical layers I-II and V-VI. PMID- 8219010 TI - Glaucomatous optic neuropathy causes sensitivity loss to light offsets in the visual field. AB - The functional integrity of the 'on' and 'off' neurovisual pathways has been examined in the central visual fields of normal (n = 13), glaucomatous (n = 21) and ocular hypertensive (n = 21) individuals. The detection thresholds to light increments (onsets = bright spots) and light decrements (offsets = dark spots) on a uniform background were determined in each eye and the visual field scores were calculated for each of the subjects. Light offsets detected the presence of glaucomatous visual loss and also revealed significant early visual deficits which were missed by the conventional light onset stimuli. This study indicates that 'off-pathway' evaluation with light offsets can be used for the assessment of the functional integrity of the visual system and may reveal sub-clinical early glaucomatous optic neuropathy. PMID- 8219009 TI - Localization and lateralization of stereoscopic processing in the human brain. AB - Positron emission tomography was used to investigate the neural substrate of stereopsis. Changes in cerebral blood flow were measured in nine volunteers while they judged the orientation of a rectangular cyclopean shape in random dot stereograms. This experimental condition was compared with two control conditions, one having a two-dimensional shape but no cyclopean stimulus, the other having neither shape nor cyclopean stimulus. Blood flow increases were observed in areas 17 and 18 in the right hemisphere when comparing experimental with control conditions; blood flow decreases occurred in the right inferotemporal cortex. Results indicate that stereopsis begins in posterior visual areas in the right cerebral hemisphere. Under ambiguous stereoscopic conditions, participation of more anterior areas in the temporal lobe may be elicited. PMID- 8219011 TI - Aluminium in rat cerebellar neural cultures. AB - A systematic microchemical analysis of unstained and uncoated neurone cultures was performed with synchrotron radiation photoemission spectromicroscopy after exposure to an aluminium solution. Clear evidence was found for localized aluminium uptake in a few cells. Their possible identification based on morphology is discussed. PMID- 8219012 TI - Synergism of tocopherol and ascorbate on the survival of cultured brain neurones. AB - The effects of antioxidants tocopherols and ascorbic acid were tested on the survival of hippocampal and striatal neurones in dissociated culture. Alpha- and gamma-tocopherol increased the number of surviving neurones in a concentration dependent manner. Significant effect was observed at concentrations of 10(-8)-10( 6) M. Furthermore, the promoting effect of alpha-tocopherol on neuronal survival was markedly enhanced in the presence of ascorbic acid (2 x 10(-6) M). These results indicate that tocopherols and ascorbic acid support the survival of cultured neurones by protecting them from oxidative attack. PMID- 8219013 TI - Cholinergic activation of phosphoinositide metabolism during soman-induced seizures. AB - In the present study we investigated the role of the cholinergic pathway in phosphoinositide metabolism activation observed during soman-induced convulsions. We thus studied the effect of atropine sulphate, a muscarinic antagonist (20 mg kg-1, i.p.), on IP3 levels in rat hippocampus. We demonstrated that initially, the increase of IP3 is closely seizure-related. On the other hand, after 10 min of seizures, the IP3 enhancement and the seizure activity are no longer correlated. After 20 min of seizures, atropine failed to inhibit soman-induced IP3 enhancement, suggesting that the activation of another neurotransmitter system(s) linked to PPI turnover succeeds the cholinergic stimulation. PMID- 8219014 TI - In vitro progesterone effects on 3H-norepinephrine release from rat cerebral cortex slices. AB - The effect of progesterone in vitro (0.05-5 microM) on K(+)-induced, Ca(2+) dependent release of 3H-NE from brain slices obtained from the occipital region of rats, during the oestrous cycle or 7 days after ovariectomy or on the fifth day of pregnancy was studied. The hormone reduced the K+ (20 mM) effect in all the stages of the cycle, but did not modify the reduced release found after ovariectomy or pregnancy or the release induced from male slices. Yohimbine blocked the effect of progesterone. The results suggest the releasing process of norepinephrine in the cerebral cortex as a target for progesterone modulatory influences on brain function. PMID- 8219015 TI - Developmental changes of growth cone gangliosides of the postnatal rat cerebrum. AB - The ganglioside content and composition of growth cones prepared from forebrains of day 0 (p0), day 2 (p2), and day 6 (p6) postnatal rats was analysed in comparison with that of whole forebrain membranes obtained from rats of the same age. The amount of total ganglioside bound sialic acid (microgram NeuAc mg protein-1) was found to increase in both whole cerebrum membranes and growth cones from p0 to p6. The ganglioside concentrations of growth cones exceeded that of the whole cerebrum by 35-40% at all time points investigated. The major rat brain gangliosides were also found in the growth cone fractions, however, in different relative amounts. Thus, the well known developmental shift from the b- to the a-ganglioside synthesis pathway was significantly delayed in growth cones, indicating that this shift is not associated with axonal growth but more likely with the subsequent period of synaptogenesis. GQ1c, recognized by the mAb Q211, and an unidentified growth-cone specific ganglioside x were found to be expressed in growth cones of p0 rats and to decrease up to p6. PMID- 8219016 TI - Botzinger expiratory neurones inhibit propriobulbar decrementing inspiratory neurones. AB - Although bulbospinal, expiratory neurones of the Botzinger complex (BOT E-AUG) are known to have monosynaptic inhibitory connections to many bulbospinal respiratory neurones, their connections to propriobulbar respiratory neurones have not been so well characterized. We stimulated BOT E-AUG neurones with trains of pulses, and found an inhibition of medullary and phrenic respiratory activity with phase resetting. We also examined the response of propriobulbar, decrementing, inspiratory neurones (I-DEC) to the antidromic activation of BOT E AUG neurones from the C3 segment of the spinal cord with single shocks and found evidence for a monosynaptic inhibition of the I-DEC neurones in the post-stimulus histograms of the extracellular firing. These results were obtained in 11 pentobarbital anaesthetized cats, and provide experimental support for a recent model of respiratory rhythmogenesis. PMID- 8219017 TI - Circling behaviour induced by activation of GABAA receptors in the subthalamic nucleus. AB - The behavioural effect of drugs acting on GABAA receptors in the subthalamic region and the entopeduncular nucleus was studied in freely moving cats. Microinjections of muscimol into the zona incerta-Forel's fields produced tilt of the head to the injected site, while injections of bicuculline or picrotoxin produced the same effect but to the opposite side. Microinjections of muscimol into the subthalamic nucleus elicited circling behaviour to the contralateral side, while bicuculline and picrotoxin produced ipsilateral turning. However, when high doses of the antagonists were injected, contralateral circling was observed. Activation or blockade of GABAA receptors into the entopeduncular nucleus was ineffective. These results imply that GABAergic mechanisms in the subthalamic nucleus and the zona incerta-fields of Forel are involved in circling behaviour and vertical head movements, respectively. PMID- 8219018 TI - c-Fos expression in the parabrachial nucleus after ingestion of sodium chloride in the rat. AB - The distribution of evoked expression of the proto-oncogene c-Fos was immunohistochemically examined in the parabrachial nucleus (PBN) of the rat after free ingestion of NaCl and some other taste solutions. C-Fos-like immunoreactive neurones (c-Fos neurones) were densely observed in the external lateral subnucleus (els), central lateral subnucleus (cls), and the central part of the medial subnucleus (ms). The finding that the number of c-Fos neurones decreased dramatically in the ms after treatment of the tongue with amiloride or after dissection of the chorda tympani suggests that the taste information of NaCl projects mainly to the ms. The functional significance of the els and cls is discussed, and it is suggested that the els is a recipient zone for general visceral inputs and the cls is concerned with palatability of the liquids ingested. The present study has proved that c-Fos immunoreactivity is a useful anatomical marker for activated neurones in the PBN during ingestive behaviour. PMID- 8219019 TI - Thalamic low threshold calcium current in a genetic model of absence epilepsy. AB - The low threshold calcium current (IT) in thalamo-cortical neurones contributes to the generation of spike and wave discharges (SWDs) characteristic of generalized, non-convulsive absence epilepsy. The biophysical properties of this current were analysed in dorsal lateral geniculate neurones from the Genetic Absence Epilepsy Rats from Strasbourg (GAERS+). No difference was found in the voltage dependence and kinetics of IT between GAERS+ and rats of the non epileptic control strain (GAERS-). Thus, a dysfunction of IT does not appear to underlie the occurrence of SWDs in absence epilepsy. PMID- 8219020 TI - [3H]-GR113808 labels 5-HT4 receptors in the human and guinea-pig brain. AB - A tritiated specific and highly potent 5-HT4 antagonist: [3H]-GR113808 was used to label specific binding sites in human brain and for comparison in guinea-pig brain. [3H]-GR113808 association and dissociation were rapid, the binding was saturable and displaced by various serotoninergic agents with an affinity corresponding to their previously reported 5-HT4 receptor mediated effects. In vitro ligand binding autoradiography was used to investigate the distribution of [3H]-GR113808 recognition sites on human brain sections. The highest density was observed in the striato-nigral system. Low densities of binding sites were also found in hippocampus, neocortex and colliculus. This distribution of [3H] GR113808 binding sites is similar to that found in the guinea-pig brain. PMID- 8219021 TI - Circadian fluctuations in GFAP distribution in the Syrian hamster suprachiasmatic nucleus. AB - We examined the possibility that astrocytes reflect mammalian circadian rhythmicity by observing the astrocytes pattern using anti-glial fibrillary acidic protein (GFAP), within the suprachiasmatic nucleus of the Syrian hamster over the 24 h cycle. Our results reveal daily systematic changes in the distribution of GFAP-immunoreactivity (GFAP-ir) both in the light/dark cycle and in constant darkness. This rhythm is characterized by a change of the GFAP-ir distribution from a network pattern to isolated cells. Such a rhythm is in synchrony with the rhythm in SCN glucose consumption which we have previously reported. This is the first time a circadian rhythm in suprachiasmatic astrocytes has been observed, indicating that GFAP-ir can be used as a novel index of clock activity. PMID- 8219022 TI - Oestrogen receptor occurrence in the male mouse brain: modulation by paternal experience. AB - Paternal behaviour (pup-searching and retrieving of pups) was studied in male house mice with different experience in pup care and oestrogen receptor immunoreactive (ER-IR) cells were localized and quantified in their brains. Experience with pups induced paternal behaviour and correlated with (a) the occurrence of ER-IR cells in the bed nucleus of the stria terminalis, hippocampus, subiculum, lateral septal nuclei, entorhinal and piriform cortex, (b) increased numbers of ER-IR cells in the medial preoptic area and arcuate nucleus of the hypothalamus, and (c) decreased presence of ER-IR cells in the periventricular grey of the midbrain. The data indicate oestrogen receptor modulation in the male brain and suggest that oestrogen binding in distinct brain areas is involved in the regulation of paternal behaviour. PMID- 8219023 TI - Extracellular pH modulates aluminium-blockade of mammalian voltage-activated calcium channel currents. AB - The pH-dependence of aluminium (Al) blockade of voltage activated calcium channels (VACCs) was investigated. Using cultures of rat dorsal root ganglion (DRG) neurones, whole-cell patch-clamp experiments were performed. Various concentrations of Al were extracellularly applied within solutions of different pH-values. The block of VACC currents was highly pH-dependent. At pH 7.3-7.8, the concentration-response curve shifted slightly to higher concentrations, whereas at pH 6.4-6.9 a pronounced shift to lower concentrations was observed. This effect could be due to changes of the chemical equilibria of the different Al species or to altered properties of the VACCs. Thus, pH-shifts may influence the interactions of Al with VACCs making them more susceptible to the effects of Al and therefore contribute to its toxicity. PMID- 8219024 TI - Effects of t-ACPD on neural survival and second messengers in cultured cerebral cortical neurones. AB - The cytotoxic potential of (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (t ACPD) in cultured murine cerebral cortical neurones was examined. Exposure to t ACPD (1 mM, 16 h) did not induce cytotoxicity per se or affect N-methyl-D aspartate-induced toxicity. Phosphoinositide hydrolysis was weakly stimulated by t-ACPD (1 mM), while no alteration of intracellular calcium levels was observed after exposure to 1 mM t-ACPD. However, forskolin-stimulated cAMP formation was inhibited by t-ACPD (IC50 = 8 +/- 2 microM) with a maximal inhibition of 36 +/- 4% of control levels. These data suggest that the lack of neurotoxic effects of t ACPD may be related to the negligible efficacy of t-ACPD to activate mGluRs coupled to the IP3/Ca(2+)-cascade and/or putative counteracting effects of t-ACPD mediated by mGluRs negatively coupled to the cAMP-cascade. PMID- 8219025 TI - AMPA, KA and NMDA receptors are expressed in the rat DRG neurones. AB - The localization of AMPA receptor subunits (GluR1-4), a KA receptor subunit (GluR5) and NMDA receptor subunits (NR1 and NRgbs; the glutamate binding subunits of an NMDA receptor complex) was investigated using immunohistochemistry and in situ hybridization histochemistry in the rat dorsal root ganglion. Small neurones expressed GluR1-, GluR2/3-like immunoreactivities and GluR5, NR1, NRgbs mRNAs, while large neurones expressed GluR2/3-like immunoreactivity and NR1 and NRgbs mRNAs. These data suggest that the glutamatergic system plays an important role in the primary sensory afferent systems and that the composition of glutamate receptors differs according to the cell size. PMID- 8219026 TI - Increased frequency of the transferrin C2 subtype in Alzheimer's disease. AB - Several genetic variants of transferrin can be separated by polyacrylamide gel isoelectric focusing. Studies by other workers have revealed that the genetic type Tf C2 has an increased frequency in certain malfunctions which are associated with the formation of free radicals, suggesting that the iron binding of Tf C2 promotes the formation of hydroxyl radicals. In our study population of 20 patients with Alzheimer's disease, 13 had the C2 genetic subtype. Since the frequency of C2 in the South African population is 0.136 (14%), this represents a significant increase (p < 0.005) in the appearance of this genetic subtype. PMID- 8219027 TI - Mental comparison: P300 component of the ERP reflects the symbolic distance effect. AB - The symbolic distance effect was studied in a numerical comparison task by means of behavioural measures and event-related potentials (ERP). Two numbers in the range from 11 to 20 were presented simultaneously and the subjects had to indicate if the right side number was smaller or larger than the left side number. Reaction time, error rate and ERPs were selectively averaged according to the numerical differences between the two numbers. The symbolic distance effect was confirmed: Reaction times and error rates decreased significantly with increasing difference between the two numbers. A significant distance effect was also found for both P300 amplitude and latency. The larger the numerical difference the larger the P300 amplitude and the P300 latency tended to be shorter. This finding suggests that the numerical difference is effective already during stimulus encoding. PMID- 8219028 TI - Interaction between representations of different features of auditory sensory memory. AB - The neurophysiological basis of sensory memory was studied by measuring the magnetic counterpart (MMNm) of the mismatch negativity (MMN) with a whole-head 122-channel magnetometer. The MMNm is a response to a difference in the presented stimulus and a neuronal memory trace formed by repeated standard stimuli. This trace must contain information about the feature differing in the deviant. Keeping one feature (frequency) constant, we studied how other stimulus features affect the strength of the MMNm. The MMNm to a frequency change was weaker when the other features varied than when they were constant. This suggests that the MMNm to a frequency change is not independent of other stimulus features. PMID- 8219029 TI - Alzheimer's disease--a spirochetosis? PMID- 8219030 TI - Spinal compensation for postural deficits after hemilabyrinthectomy? AB - Removal of the labyrinthine organs on one side results in static and dynamic disturbances. Some functional recovery occurs over time and is paralleled in frogs by an increase in the efficacy of central vestibular pathways. Here, we report concomitant increases in dorsal root evoked ventral root responses in the brachial spinal cord and compare the time courses of neural changes in the brain stem and in the spinal cord with the progress of postural recovery in frogs. From this comparison we conclude that postural deficits are compensated by a spinal substitution process on the operated side. PMID- 8219031 TI - Induction of c-fos mRNA in the brain and anterior pituitary gland by a novel environment. AB - To determine the cell groups which are activated by novelty stress, we examined the induction of c-fos mRNA in brain tissues following introduction of male rats to a novel open field. Male Fischer 344 rats were placed in a brightly lit open field and allowed to roam free for 20 min. Control animals were sacrificed upon removal from their home cage. Northern blot analysis revealed a 2.2 kb hybridization signal which increased in density following novelty. In situ hybridization analysis showed that c-fos mRNA was induced in a specific pattern consistent with the behavior. The regions of induction included the medial prefrontal and orbital cortex, cingulate and parietal cortex, hippocampal CA1 and CA3 pyramidal cell regions, dorsal and ventral anterior thalamic n. and paraventricular n. of the hypothalamus. C-fos mRNA also increased in the anterior pituitary gland and this increase correlated with the secretion of ACTH. These data demonstrate the brain areas undergoing genomic activation following complex behavior paradigms such as introduction to a novel environment. PMID- 8219032 TI - Amblyopia and suppression in binocular cortical neurones of strabismic cat. AB - The neural mechanism of strabismic amblyopia was investigated by recording the spatio-temporal properties of striate cortical neurones of cats raised with a surgically induced esotropia. Multiple pseudo-random flashed or phase-alternating stimuli were used, and through cross-correlation, the Wiener kernels were extracted. This analysis has shown that in neurones which retain binocularity to adulthood, two different neural mechanisms of adaptation to ocular misalignment exist. Some of these neurones become amblyopic, such that the non-deviating eye dominates the response for high spatial frequencies while the strabismic eye dominates at low spatial frequencies. Other neurones adapt through active suppression of the monocular response to stimulation of the strabismic eye when the non-deviating eye is simultaneously stimulated. PMID- 8219033 TI - Transient elevation in catalytic trkB mRNA during postnatal development of the rat brain. AB - Quantitative in situ hybridization analysis of catalytic (trkB TK+) and non catalytic (trkB TK-) trkB mRNAs in the postnatal rat brain demonstrated regional differences in expression and revealed transient increases in trkB TK+ expression. Hybridization of trkB TK+ mRNA was observed in thalamic nuclei between P4 and P8, but not in the adult. In hippocampal structures, transient elevations of trkB TK+ mRNA were apparent between P13 and P17. In contrast, there was a gradual developmental increase in trkB TK- mRNA expression in the hippocampus. PMID- 8219034 TI - Diurnal variations in the feeding response to 8-OH-DPAT injected into the dorsal or median raphe. AB - To determine the impact on food intake of the 5-HT1A agonist, 8-OH-DPAT, administered at various times throughout the nocturnal cycle, rats were implanted with cannulae in either the dorsal or median raphe nuclei and injected with saline or 8-OH-DPAT (0.4, 0.8 or 1.6 nmol) immediately following dark onset, or during the mid or late dark periods. 8-OH-DPAT potentiated feeding when administered in the mid or late dark phase, whereas treatment during the early dark actually suppressed food intake. These findings indicate that the feeding responses to dorsal and median raphe 8-OH-DPAT vary greatly depending on the time of administration in the diurnal cycle and are consistent with recent reports of a biphasic action of this compound on ingestive behaviour. PMID- 8219035 TI - Effect of electroconvulsive shock treatment on the opioid-mediated inhibition of serotonin release in rat hippocampal slices. AB - We investigated the influence of electroconvulsive shock treatment on the opioid mediated inhibition of serotonin (5-HT) release. The overflow of [3H]serotonin elicited by high potassium (30 mM) in superfused slices of rat hippocampus was significantly inhibited in the presence of two agonists, mu-selective [D-Ala2,N methyl-Phe4,Gly5ol]enkephalin (DAGO) and delta-selective [D-Pen2,D Pen5]enkephalin (DPDPE) in control animals. The repeated (once daily for 7 days) electroconvulsive shock treatment significantly reversed the inhibitory effect of both DAGO and DPDPE. Single electroconvulsive shock (1 day) had no effect on DAGO inhibition, on the contrary a trend to antagonism of the DPDPE effect was reported. These results suggested that the opioids are associated with the experimental induced seizures and that the ECS treatment might regulate the serotonin release throughout the opioid receptor system. PMID- 8219036 TI - Effects of IGF-1, truncated IGF-1 and the tripeptide Gly-Pro-Glu on acetylcholine release from parietal cortex of rat brain. AB - The effects of intact IGF-1, truncated IGF-1 and Gly-Pro-Glu (GPE), the aminoterminal tripeptide of IGF-1, on the potassium (35 mM K+) stimulated release of acetylcholine (ACh) from rat cortical slices were investigated. GPE significantly increased the release of ACh in the dose range of 10(-10)-10(-6) M, while IGF-1 significantly enhanced the release of ACh only at 4 x 10(-8) M. The truncated form of IGF-1, lacking the tripeptide GPE, did not effect the release of ACh in rat cortex. Binding experiments also showed that truncated IGF-1 was less available to the brain slices. The possible underlying mechanisms of action of GPE in the cholinergic synapse were investigated. GPE (10(-5) M) significantly (40%) displaced [3H]nicotine from its binding sites in rat cortex. In the concentration range of 10(-10)-10(-5) M, GPE did not interact with the choline uptake sites ([3H]hemicholinium binding) or the muscarinic ([3H]QNB) receptor binding sites in rat cortex. The mechanism of action behind GPEs enhancement of cholinergic transmission is therefore still unknown. PMID- 8219038 TI - Glycine-immunoreactive neurones in the cat brain stem reticular formation. AB - Using a specific glycine antiserum, we determined the localization of glycinergic neurones and fibres in the cat brain stem reticular formation. We visualized a large number of glycine-immunoreactive cell bodies and fibres in the medullary reticularis gigantocellularis, magnocellularis, paragigantocellularis lateralis and parvocellularis nuclei. The pontis oralis and caudalis and the raphe magnus nuclei also contained a large number of glycine-immunoreactive fibres but fewer neurones. Using a double staining method, we further observed glycine immunoreactive boutons over (1) noradrenergic neurones in the locus coeruleus complex and the ventrolateral and dorsomedial medulla, (2) serotoninergic neurones in and outside the raphe nuclei and (3) cholinergic neurones in the pedunculopontine and laterodorsal tegmental nuclei. These results suggest that glycinergic neurones in the reticular formation may be involved in aspects of paradoxical sleep, including the general muscle atonia seen during this sleep state. PMID- 8219037 TI - Deposition of aluminum in brain tissues of rats exposed to inhalation of aluminum acetylacetonate. AB - The present paper reports data concerning aluminum accumulation and compartmentation in the central nervous system from rats exposed by inhalation to aluminum acetylacetonate [Al(acac)3] for two weeks. The complex Al(aca)3 was chosen for being neutral, hydrolytically stable and lipophilic. After animals treatment, Al(III) was identified fluorimetrically by using morin (3,5,7',2',4' pentahydroxyflavone) that gives a specific green-yellow fluorescence when complexed to the metal. Al(III) was observed to be accumulated in the brain cortex, hippocampus, enthorinal area, olfactory bulb as well as in the Purkinje cells of cerebellum, and in the white matter. PMID- 8219039 TI - Bilateral control of the orbicularis oculi muscle by one cerebellar hemisphere in the ferret. AB - Reports that lesions of the anterior interpositus nucleus in the cerebellum or of the cerebellar cortex abolish classically conditioned eyeblink responses were originally taken to indicate that the cerebellum is the locus of learning. This interpretation has recently been questioned by reports that conditioned responses may recover after ipsilateral cerebellar lesions. It cannot be excluded, however, that the recovered responses were produced by the intact contralateral hemisphere. In order to determine if cerebellar outflow to the orbicularis oculi muscle is bilateral, we stimulated both the brachium conjunctivum and a cortical area in the c3 zone of the cerebellar cortex which controls eyeblink. Both kinds of stimulation elicited EMG activity in both the ipsi- and the contralateral eyelids. The results thus show that there is a bilateral control of eyeblink from each cerebellar hemisphere and they raise the possibility that recovery of conditioning after ipsilateral cerebellar lesions is due to the intact hemisphere. Reports of such recovery after unilateral lesions are therefore inconclusive. PMID- 8219040 TI - Nitric oxide and long-term synaptic depression in the rat hippocampus. AB - Stimulation of the Schaffer collateral projection to the CA1 region in rat hippocampal slices at 1 Hz for 15 min produced a N-methyl-D-aspartate (NMDA) receptor-dependent long-term depression (LTD) of synaptic responses and, when given after tetanic stimulation, reversed long-term potentiation (LTP). Both LTD and the reversal of LTP were blocked by the nitric oxide (NO) inhibitor L-NG monomethylargine (L-NMMA). L-NG-nitroarginine (L-NOArg) and hemoglobin also blocked LTD. The inhibition of LTD by L-NMMA was overcome by L- but not D arginine. Sodium nitroprusside and S-nitrosocysteine, agents that spontaneously release NO, mimicked the effect of 1 Hz stimulation. These results indicate that NO mediates LTD produced by sustained 1 Hz activation of CA1 synapses and support the hypothesis that NO mediates the inhibition of LTP produced by untimely activation of NMDA receptors. PMID- 8219041 TI - Potentiation of synaptic transmission by neuropeptide AVP4-8 (ZNC(C)PR) in rat hippocampal slices. AB - The effect of AVP4-8 on synaptic transmission in rat hippocampal slices was studied using both extracellular and intracellular recording. AVP4-8 induced a long-lasting potentiation effect on the evoked EPSP and enhanced LTP in pyramidal neurones. The lowest effective concentration of AVP4-8 was 1 x 10(-12) M, three to four orders of magnitude lower than that of AVP. These findings support the concept that AVP4-8 is a new memory-enhancing peptide and should be written as ZNC(C)PR. The results show that the potentiation effect of ZNC(C)PR is mainly due to a presynaptic mechanism of action. PMID- 8219042 TI - Down-regulation of two non-homologous endogenous tomato genes with a single chimaeric sense gene construct. AB - Tomatoes (Lycopersicon esculentum Mill cv. Ailsa Craig) were transformed with a gene construct having 244 bp of the 5' end of a polygalacturonase (PG) cDNA, coding for a 71 amino acid N-terminal extension to the mature protein, fused to 1320 bp of a pectin-esterase (PE) cDNA encoding the full sequence of the mature PE protein. This chimaeric gene was inserted in a sense orientation between a CaMV 35S promoter and terminator for constitutive expression. In transformed tomato plants expression of the endogenous PG and PE genes in the fruit was inhibited; there was little or no observable PG and PE mRNA and a substantial reduction in the level of PG and PE enzyme activity. The transgene was expressed in the leaves of the transformed plants as demonstrated by the accumulation of mRNA, but no protein product could be identified. However, no transgene mRNA or protein were observed in the transgenic fruit. The paper represents the first report of the down-regulation of two non-homologous endogenous genes using a single gene construct. A sense gene construct was responsible for these effects. These findings are discussed in relation to possible mechanisms of action of co suppression. PMID- 8219043 TI - Increased production of cadaverine and anabasine in hairy root cultures of Nicotiana tabacum expressing a bacterial lysine decarboxylase gene. AB - Several hairy root cultures of Nicotiana tabacum varieties, carrying two direct repeats of a bacterial lysine decarboxylase (ldc) gene controlled by the cauliflower mosaic virus (CaMV) 35S promoter expressed LDC activity up to 1 pkat/mg protein. Such activity was, for example, sufficient to increase cadaverine levels of the best line SR3/1-K1,2 from ca. 50 micrograms (control cultures) to about 700 micrograms/g dry mass. Some of the overproduced cadaverine of this line was used for the formation of anabasine, as shown by a 3-fold increase of this alkaloid. In transgenic lines with lower LDC activity the changes of cadaverine and anabasine levels were correspondingly lower and sometimes hardly distinguishable from controls. Feeding of lysine to root cultures, even to those with low LDC activity, greatly enhanced cadaverine and anabasine levels, while the amino acid had no or very little effect on controls and LDC-negative lines. PMID- 8219044 TI - Expression of heat shock proteins during development of barley. AB - Barley heat shock proteins have been cloned, characterized by hybrid release translation and sequenced. Clones coding for proteins of 17, 18, 30, 32 and 70 kDa have been obtained. Out of these the 32 and 30 kDa proteins have been characterized as precursors to plastidic proteins of 26 kDa by posttranslational transport and by cDNA sequencing. The coding regions of these two transcribed genes are highly homologous. Accumulation of the plastid HSP as well as of HSP 70 as well as their corresponding mRNAs has been studied in 2- to 6-day old seedlings and in the 7-day old barley leaf. The mRNA for all investigated proteins were only found after a heat shock; the mRNA levels increase towards the tip of the leaf and with development. Furthermore, under the conditions used the mRNAs for all investigated heat shock proteins accumulate in parallel. Unexpectedly, both proteins, HSP 70 and HSP 26, are found by western blotting in the 2-day old control plants in the absence of any inducing heat shock. At later stages of development and in the leaf gradient only immunoreactivity with HSP 70 was observed. In contrast to the levels of their mRNAs the highest levels of HSP 30-26 and 70 have been observed in the basal segments indicating that translational control plays a role during HSP expression. Under severe heat shock a protein of 30 kDa is induced whose identity is not known but which reacts with the antibody to HSP 30-26 and might represent the accumulating precursors of the plastidic proteins. PMID- 8219045 TI - Deletion mutations in a long hydrophilic loop in the photosystem II chlorophyll binding protein CP43 in the cyanobacterium Synechocystis sp. PCC 6803. AB - In order to investigate the role and function of the hydrophilic region between transmembrane regions V and CI in the photosystem II core antenna protein CP43, we introduced eight different deletions in psbC of Synechocystis sp; PCC 6803 resulting in a loss of 7-11 codons in evolutionary conserved domains in this region. All deletions resulted in an obligate photoheterotrophic phenotype (requirement of glucose for cell growth) and the absence of any detectable oxygen evolution activity. The various deletion mutations showed a different impact on the amount of CP43 in the thylakoid, ranging from wild-type levels of (a now slightly smaller) CP43 to no detectable CP43 at all. All deletions led to a decrease in the amount of the D1 and D2 proteins in the thylakoids with a larger effect on D2 than on D1. CP47, the other major chlorophyll-binding protein, was present in reduced but significant amounts in the thylakoid. Herbicide binding (diuron) was lost in all but one mutant indicating the PSII components are not assembled into functionally intact complexes. Fluorescence-emission spectra confirmed this notion. This indicates that the large hydrophilic loop of CP43 plays an important role in photosystem II, and even though a shortened CP43 is present in thylakoids of most mutants, functional characteristics resembled that of a mutant with interrupted psbC. PMID- 8219046 TI - Molecular cloning, sequence analysis and elicitor-/ozone-induced accumulation of cinnamyl alcohol dehydrogenase from Norway spruce (Picea abies L.). AB - Cinnamyl alcohol dehydrogenase (CAD) is an enzyme involved in lignin biosynthesis. We have previously isolated pure CAD enzyme from Norway spruce (Picea abies L.) cell culture. Here we report on partial protein sequences of the 42 kDa CAD polypeptide. A cDNA encoding CAD was isolated from the spruce cell culture. The open reading frame of a full-length cDNA coded for a 357 amino acid polypeptide with a calculated M(r) of 38,777 Da. The identity of the deduced polypeptide was verified by comparison with amino acid sequences of tryptic peptides from the purified enzyme. Southern blot analysis showed the presence of only one gene for CAD. Sequence comparison with CAD from tobacco and with a N terminal protein sequence from loblolly pine CAD showed an identity of 69.7% and 91.5%, respectively. Treatment of spruce cell cultures with elicitor, as well as of seedlings with ozone both markedly increased the CAD mRNA level. PMID- 8219047 TI - Definition and characterization of an artificial En/Spm-based transposon tagging system in transgenic tobacco. AB - A transposon tagging system for heterologous hosts, based on the maize En/Spm transposable element, was developed in transgenic tobacco. In this system, the two En-encoded trans-acting factors necessary for excision are expressed by fusing their cDNAs to the CaMV 35S promoter. The dSpm receptor component is inserted in the 5'-untranslated leader of the bar gene. Germinal revertants can therefore be selected by seed germination on L-PPT-containing medium or by spraying seedlings with the herbicide Basta. Using this bar-based excision reporter construct, an average frequency of germinal excision of 10.1% was estimated for dSpm-S, an En/Spm native internal deletion derivative. Insertion of En-foreign sequences in a receptor, such as a DHFR selectable marker gene in dSpm DHFR, does not abolish its capacity to transpose. However, dSpm-DHFR has a lower frequency of somatic and germinal excision than dSpm-S. Revertants carrying a transposed dSpm-DHFR element can be selected with methotrexate. Germinal excision is frequently associated with reinsertion but, as in maize, dSpm has a tendency to integrate at chromosomal locations linked to the donor site. Concerning the timing of excision, independent germinal transpositions are often found within a single seed capsule. All activity parameters analysed suggest that transposon tagging with this system in heterologous hosts should be feasible. PMID- 8219048 TI - A point mutation in the chloroplast rps12 gene from Nicotiana plumbaginifolia confers streptomycin resistance. AB - In an effort to understand the mechanism of streptomycin resistance in Nicotiana plumbaginifolia, we have sequenced the chloroplast rps12 gene, a potential molecular target. We report that a streptomycin-resistant mutant isolated from protoplast cultures of N. plumbaginifolia contains an A-to-G transition at nucleotide position 149 in exon 2 of the chloroplast rps12 gene. The detected point mutation predicts a substitution of arginine for lysine in a phylogenetically conserved region. PMID- 8219049 TI - cDNA cloning and characterisation of novel ripening-related mRNAs with altered patterns of accumulation in the ripening inhibitor (rin) tomato ripening mutant. AB - A cDNA library produced from mRNA isolated from the pericarp of wild-type tomato fruit (Lycopersicon esculentum Mill. cv Ailsa Craig) at the first visible sign of fruit ripening was differentially screened to identify clones whose homologous mRNAs were present at reduced levels in fruit of the tomato ripening mutant, ripening inhibitor,rin. Five clones were isolated (pERT 1, 10, 13, 14, 15). Accumulation of mRNA homologous to each of these clones increased during the ripening of wild-type fruit and showed reduced accumulation in ripening rin fruit. The levels of three of them (homologous to ERT 1, 13 and 14) were increased by ethylene treatment of the mutant fruit. A further clone, ERT 16 was identified for a mRNA present at a high level in both normal and mutant fruit at early stages of ripening. Database searches revealed no significant homology to the DNA sequence of ERT 14 and 15; however, DNA and derived amino acid sequence of ERT 1 both contain regions of homology with several reported UDP-glucosyl and glucuronosyl transferases (UDPGT) and with a conserved UDPGT motif. A derived amino acid sequence from the ERT 10 cDNA contains a perfect match to a consensus sequence present in a number of dehydrogenases. The ERT 13 DNA sequence has homology with an mRNA present during potato tuberisation. The presence of these mRNAs in tomato fruit is unreported and their role in ripening is unknown. The ERT 16 DNA sequence has homology with a ripening/stress-related cDNA isolated from tomato fruit pericarp. PMID- 8219050 TI - Can lysozymes mediate antibacterial resistance in plants? PMID- 8219051 TI - The resistance of cowpea seeds to bruchid beetles is not related to levels of cysteine proteinase inhibitors. AB - A cDNA encoding a cysteine proteinase inhibitor was isolated from a cDNA library prepared from developing seeds of an insect-resistant line of cowpea. The sequence of the encoded protein was homologous with those of other plant cysteine endoproteinase inhibitors, and with Type 2 cystatins from animals. Southern blot analyses indicated that small gene families were present in both resistant and susceptible lines of cowpea, while northern blot analyses showed similar levels of expression. It is concluded that the levels of expression of the inhibitor do not account for the differences in insect resistance of the two lines. PMID- 8219052 TI - A low-temperature-responsive translation elongation factor 1 alpha from barley (Hordeum vulgare L.). AB - A cDNA clone (pBLT63) encoding a protein synthesis elongation factor 1 alpha (EF 1 alpha) was isolated from a low-temperature winter barley shoot meristem library by differential screening. The nucleotide sequence of the coding region of the low-temperature-induced barley gene shows very high homology with two EF-1 alpha plant genes from tomato and Arabidopsis. The barley genome contains an EF-1 alpha gene family situated on the short arm of chromosome 2 and the long arm of chromosome 5. PMID- 8219053 TI - Isolation and analysis of a cDNA clone encoding the small subunit of ADP-glucose pyrophosphorylase from wheat. AB - A full-length cDNA clone from hexaploid bread wheat, encoding the small subunit of ADP-glucose pyrophosphorylase, has been isolated from an endosperm cDNA library. The cDNA insert has an open reading frame which encodes a protein of 473 amino acids (52.1 kDa). The presence of a chloroplast/amyloplast transit peptide of 22 amino acids is proposed. The deduced amino acid sequence exhibits a high degree of homology with the small subunit ADP-glucose pyrophosphorylase proteins from rice (with 90% of identical amino acids) and potato (with 86% of identical amino acids) and contains conserved sequence elements which are thought to represent the substrate binding and allosteric activator sites. The genes are organised as single-copy loci on chromosomes 7A, 7B and 7D in the wheat genome and are highly expressed during grain development. Homologous transcripts are expressed in leaves and roots. PMID- 8219054 TI - A soybean coproporphyrinogen oxidase gene is highly expressed in root nodules. AB - In plants the enzyme coproporphyrinogen oxidase catalyzes the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX in the heme and chlorophyll biosynthesis pathway(s). We have isolated a soybean coproporphyrinogen oxidase cDNA from a cDNA library and determined the primary structure of the corresponding gene. The coproporphyrinogen oxidase gene encodes a polypeptide with a predicted molecular mass of 43 kDa. The derived amino acid sequence shows 50% similarity to the corresponding yeast amino acid sequence. The main difference is an extension of 67 amino acids at the N-terminus of the soybean polypeptide which may function as a transit peptide. A full-length coproporphyrinogen oxidase cDNA clone complements a yeast mutant deleted of the coproporphyrinogen oxidase gene, thus demonstrating the function of the soybean protein. The soybean coproporphyrinogen oxidase gene is highly expressed in nodules at the stage where several late nodulins including leghemoglobin appear. The coproporphyrinogen oxidase mRNA is also detectable in leaves but at a lower level than in nodules while no mRNA is detectable in roots. The high level of coproporphyrinogen oxidase mRNA in soybean nodules implies that the plant increases heme production in the nodules to meet the demand for additional heme required for hemoprotein formation. PMID- 8219055 TI - Conditional inhibition of beta-glucuronidase expression by antisense gene fragments in petunia protoplasts. AB - Antisense RNA-mediated inhibition of gene expression is a valuable tool to induce mutant phenotypes. We are interested in the application of antisense gene fragments with the aim to improve the efficiency of inhibition and to be able to selectively suppress gene family members in plants. Protoplasts may provide a rapid system to screen the efficiency of antisense gene segments. As a first step, we set up a transient expression system for leaf protoplasts of Petunia hybrida and used as a model system the inhibition of beta-glucuronidase (uidA) expression by uidA antisense gene segments. Both GUS enzyme activities and uidA RNA levels were measured. Co-introducing equal amounts of a full-length uidA antisense gene and a uidA sense gene reduced GUS activity by 60-70%. Various uidA antisense fragments also inhibited expression although with different efficiencies and we show that strong antisense fragments can be retrieved from weak antisense gene fragments. A promoter-less antisense gene did not reduce uidA expression indicating that the inhibition is mediated by antisense transcripts. Using quantitative PCR on first-strand cDNA we show that expression of functional antisense genes lead to reduced levels of uidA mRNA. This suggests that the mechanism of antisense RNA inhibition in protoplasts is similar to that in transgenic plants and that the protoplast system in combination with PCR can be used to preselect antisense fragments of any gene. PMID- 8219056 TI - Two members of the ERabp gene family are expressed differentially in reproductive organs but to similar levels in the coleoptile of maize. AB - A Zea mays cDNA clone, ZmERabp4, coding for a new member of the auxin-binding protein family was isolated. The primary amino acid sequence contains an N terminal hydrophobic leader sequence, a potential glycosylation site (Asn136-Thr Thr) and a C-terminal KDEL motif known to be responsible for retention of proteins within the lumen of the ER. The expression pattern of the ZmERabp4 gene in various organs of maize differs from the expression pattern previously observed for the ZmERabp1 gene. The ZmERabp4 gene is expressed highly in male flower organs, whereas the ZmERabp1 gene shows highest expression in female flower parts. In situ hybridization and analysis by laser scanning microscopy revealed enhanced levels of expression for both genes in the coleoptile when compared with the primary leaf of etiolated maize seedlings. PMID- 8219057 TI - Organization of plastid-encoded ATPase genes and flanking regions including homologues of infB and tsf in the thermophilic red alga Galdieria sulphuraria. AB - We have cloned and sequenced the plastid ATPase operons (atp1 and atp2) and flanking regions from the unicellular red alga Galdieria sulphuraria (Cyanidium caldarium). Six genes (5 atpI, H, G, F, D and A 3) are linked in atp1 encoding ATPase subunits a, c, b, b, delta and alpha, respectively. The atpF gene does not contain an intron and overlaps atpD by 1 bp. As in the genome of chloroplasts from land plants, the cluster is located downstream of rps2, but between this gene and atp1 we found the gene for the prokaryotic translation elongation factor TS. Downstream of atpA, we detected two open reading frames, one encoding a putative transport protein. The genes atpB and atpE, encoding ATPase subunits beta and epsilon, respectively, are linked in atp2, separated by a 2 bp spacer. Upstream of atpB, an uninterrupted orf167 was detected which is homologous to an intron-containing open reading frame in land plant chloroplasts. This orf167 is preceded on the opposite DNA strand by a homologue to initiation factor 2 in prokaryotes. The arrangement of atp1 and atp2 is the same as observed in the multicellular red alga Antithamnion sp., indicating a conserved genome arrangement in the red algal plastid genome. Differences compared to green chloroplast genomes suggest a large phylogenetic distance between red algae and green plants, while similarities in arrangement and sequence to chromophytic ATPase operons support a red algal origin of chlorophyll a/c-containing plastids or alternatively point to a common prokaryotic endosymbiont. PMID- 8219058 TI - Glutamate synthase is plastid-encoded in a red alga: implications for the evolution of glutamate synthases. AB - An actively transcribed gene (glsF) encoding for ferredoxin-dependent glutamate synthase (Fd-GOGAT) was found on the plastid genome of the multicellular red alga Antithamnion sp. Fd-GOGAT is not plastid-encoded in chlorophytic plants, demonstrating that red algal plastid genomes encode for additional functions when compared to those known from green chloroplasts. Moreover, our results suggest that the plant Fd-GOGAT has an endosymbiotic origin. The same may not be true for NADPH-dependent GOGAT. In Antithamnion glsF is flanked upstream by cpcBA and downstream by psaC and is transcribed monocistronically. Implications of these results for the evolution of GOGAT enzymes and the plastid genome are discussed. PMID- 8219059 TI - Posttranscriptional accumulation of chloroplast tufA (elongation factor gene) mRNA during chloroplast development in Chlamydomonas reinhardtii. AB - Light induces chloroplast (Cp) differentiation in dark-grown y-1 strains of Chlamydomonas reinhardtii. Slot blot analysis was used to quantitate tufA, psbA, psbK, rbcL, and 16S rRNA transcript accumulation and transcription during Cp differentiation. When etiolated cc-125 y-1 cells were illuminated for 5 h, a 1710 bp tufA mRNA accumulated up to 5-fold while the psbA, rbcL, and 16S rRNA transcripts accumulated less than 1.5-fold. The tufA gene encodes translational elongation factor EF-Tu. The light-induced accumulation of tufA mRNA did not occur in cc-1931, a strain that does not become etiolated in darkness. Pulse labelling was used to measure the transcription of Cp transcripts during tufA mRNA accumulation, and no detectable change in tufA transcription was observed. These results imply that the half life of the tufA transcript increases during the greening process. PMID- 8219060 TI - Plant viral leaders influence expression of a reporter gene in tobacco. AB - In order to optimise expression of a foreign protein in transgenic plants we investigated the potential benefits of including a viral untranslated leader sequence within a plant transformation vector. A variety of 5 leaders, including the tobacco mosaic virus (TMV) leader sequence and 31 nucleotides of the cauliflower mosaic virus (CaMV) 35S RNA leader, were compared. Viral leader constructs employing the 35S promoter and the reporter beta-glucuronidase (GUS) were tested by electroporation into tobacco mesophyll protoplasts and against a cointroduced chloramphenicol acetyl transferase (CAT) gene in transgenic tobacco leaves. In the transient assay system, GUS activities from the viral leaders were compared with those from either a short, random leader or a translational fusion of the CaMV 19S RNA ORF VI to GUS. A two- to-three-fold enhanced level of expression resulted when these leaders were substituted with either the 35S RNA or the TMV leader sequences. This enhancement was further increased, to four- to five-fold, by inclusion of four or seven of the bases from the 35S transcription initiation site adjacent to the TMV leader. In transgenic tobacco the improved GUS levels were maintained from constructs including either the TMV leader (eight fold) or this sequence with the addition of the 35S transcription initiation site bases (ten-fold). A comparison of GUS enzyme amounts with GUS mRNA amounts, using the CAT gene as an internal standard, revealed that TMV leader-bearing mRNA was translated from four- to six-fold more efficiently than the random leader control. PMID- 8219061 TI - Invertase encoding cDNA from oat. PMID- 8219062 TI - Characterization of tomato DNA clones with sequence similarity to human minisatellites 33.6 and 33.15. AB - A tomato lambda genomic library was screened with the human minisatellites 33.6 and 33.15. Similar tomato sequences are estimated to occur on average every 4000 kb. In thirteen hybridizing clones characterized, the size of minisatellite arrays varied between 100 bp and 3 kb. The structure of the repetitive elements is complex as the human core sequence is interspersed with other elements. In three cases, sequences similar to the human minisatellites were part of a higher order tandem repeat. The chromosomal position of these sequences was established by ascertaining linkage to previously mapped RFLP markers. In contrast to the human genome, no clustering of minisatellite loci was observed in tomato. The fingerprints generated by hybridizing tomato minisatellites to genomic DNA of a set of cultivars were, in two cases, more variable than those obtained with 33.6 or 33.15. Two of the characterized probes detected 4-8 alleles of a single locus, which displayed 10-15 times more polymorphism than random RFLP clones. Some minisatellites contain di- and tri-nucleotide microsatellite repeated motifs which may account for the high level of polymorphism detected with these clones. PMID- 8219063 TI - A leaf-specific gene stimulated by light during wheat acclimation to low temperature. AB - We report here the identification and characterization of a new leaf-specific light-stimulated gene induced during cold acclimation of wheat. Sequence analysis revealed that the gene encodes a protein of 19 kDa with a pI of 8.8. This is a novel protein with a particular charge distribution. The C-terminal half has a high propensity to form an alpha-helix and contains all the acidic amino acids with a net negative charge of -7. On the other hand, the N-terminal half is rich in proline, lysine and arginine with a net positive charge of +10. These properties are commonly found in several transcription factors. The protein is also rich in alanine (21%), is hydrophilic but not boiling soluble in contrast to other alanine-rich proteins. During low temperature exposure, the corresponding mRNA accumulates rapidly in the leaf and remains at a constant level in two tolerant cultivars used. However, in a less tolerant cultivar, the mRNA level declines despite maintaining the plants at 4 degrees C. Southern blot analysis indicates that the differential expression in the less tolerant genotype is not due to a different genomic organization or gene copy number. The mRNA was specifically localized in leaf tissues and increased several-fold during the greening at 4 degrees C. Furthermore, this gene is not induced in callus cultures acclimated in the absence or presence of light. This suggests that the full expression of this gene is dependent on organized leaf tissue. The expression of this gene was not affected by ABA, drought, heat shock, salinity, wounding or anaerobiosis, demonstrating that it is specifically induced by low temperature. The Wcs19 mRNA is preferentially expressed in tolerant Gramineae species. PMID- 8219064 TI - Molecular cloning, characterization and expression of Mn-superoxide dismutase from the rubber tree (Hevea brasiliensis). AB - A genomic clone encoding manganese-containing superoxide dismutase (SOD; EC 1.15.1.1) was isolated from a Hevea brasiliensis genomic library made in lambda phage EMBL3 by using a heterologous cDNA probe of MnSOD from Nicotiana plumbaginifolia. The nucleotide sequence of 4968 bp from the genomic clone was determined. Based on the putative translation initiation codon and stop codon, PCR primers were designed and utilized for cloning the full-length cDNA from total mRNA. Of the two distinct cDNAs of MnSOD isolated, MnSOD-A has a perfect match with exons of the nuclear gene, while MnSOD-B has a 90.2% homology and is 6 nucleotides longer than MnSOD-A in the putative transit peptide region. The nuclear gene comprises 6 exons and 5 introns, giving a total length of 3211 bp. The sequences of 1400 bp upstream of the initiation codon and 320 bp downstream of the stop codon were also determined. Southern analysis of genomic DNA from Hevea probed with a genomic fragment indicated there are at least two genes of MnSOD in Hevea. Northern blot analysis showed that MnSOD transcripts were present in all tissues examined (leaf, petiole, root, latex, callus) with young leaves showing the highest levels in intact plants. The transcript level in embryogenic callus was nearly 50-fold higher than in mature leaves. In addition, transcripts of MnSOD could be induced 3- to 5-fold in response to sucrose, ethephon and Murashige-Skoog salts. PMID- 8219065 TI - The plant mitochondrial open reading frame orf221 encodes a membrane-bound protein. AB - We have shown that the open reading frame orf221 is an active mitochondrial gene which encodes a novel mitochondrial polypeptide. The orf221 sequence is common to higher plants but absent in animal and fungal mitochondria. A mitochondrial polypeptide with an apparent molecular weight of 21,000 was detected with a polyclonal antibody raised against an ORF221 fusion protein. In organello translation followed by immunoprecipitation with the anti-ORF221 antibody demonstrated that this polypeptide is encoded by the orf221 gene in plant mitochondria. The ORF221 was found to be a mitochondrial membrane protein in normal (N), cms-T, and cms-C cytoplasms of several inbred lines of maize (Zea mays L.) and in other plant species. PMID- 8219066 TI - Chloroplast chlB gene is required for light-independent chlorophyll accumulation in Chlamydomonas reinhardtii. AB - Light-independent chlorophyll synthesis occurs in some algae, lower plants, and gymnosperms, but not in angiosperms. We have identified a new chloroplast gene, chlB, that is required for the light-independent accumulation of chlorophyll in the green alga Chlamydomonas reinhardtii. The chlB gene was cloned, sequenced, and then disrupted by performing particle gun-mediated chloroplast transformation. The resulting homoplasmic mutant was unable to accumulate chlorophyll in the dark and thus exhibited a 'yellow-in-the-dark' phenotype. The chlB gene encodes a polypeptide of 688 amino acid residues, and is distinct from two previously characterized chloroplast genes (chlN and chlL) also required for light-independent chlorophyll accumulation in C. reinhardtii. Three unidentified open reading frames in chloroplast genomes of liverwort, black pine, and Chlamydomonas moewusii were also identified as chlB genes, based on their striking sequence similarities to the C. reinhardtii chlB gene. A chlB-like gene is absent in chloroplast genomes of tobacco and rice, consistent with the lack of light-independent chlorophyll synthesis in these plants. Polypeptides encoded by the chloroplast chlB genes also show significant sequence similarities with the bchB gene product of Rhodobacter capsulatus. Comparisons among the chloroplast chlB and the bacterial bchB gene products revealed five highly conserved sequence areas that are interspersed by four stretches of highly variable and probably insertional sequences. PMID- 8219067 TI - A strong protein unfolding activity is associated with the binding of precursor chloroplast proteins to chloroplast envelopes. AB - Protein conformational changes related to transport into chloroplasts have been studied. Two chimaeric proteins carrying the transit peptide of either ferredoxin or plastocyanin linked to the mouse cytosolic enzyme dihydrofolate reductase (EC 1.5.1.3.) were employed. In contrast to observations in mitochondria, we found in chloroplasts that transport of a purified ferredoxin-dihydrofolate reductase fusion protein is not blocked by the presence of methotrexate, a folate analogue that stabilizes the structural conformation of dihydrofolate reductase. It is shown that transport competence of this protein in the presence of methotrexate is not a consequence of alteration of the folding characteristics or methotrexate binding properties of dihydrofolate reductase by fusion to the ferredoxin transit peptide. Binding of dihydrofolate reductase fusion proteins to chloroplast envelopes is not inhibited by low temperature and it is only partially diminished by methotrexate. It is demonstrated that the dihydrofolate reductase fusion proteins unfold, despite the presence of methotrexate, on binding to the chloroplast envelopes. We propose the existence of a strong protein unfolding activity associated to the chloroplast envelopes. PMID- 8219068 TI - Cytokinin-mediated insect resistance in Nicotiana plants transformed with the ipt gene. AB - The bacterial isopentenyl transferase (ipt) gene involved in cytokinin biosynthesis was fused with a promoter from the proteinase inhibitor II (PI-IIK) gene and introduced into Nicotiana plumbaginifolia. Transcripts of the ipt gene were wound-inducible in leaves of transgenic PI-II-ipt plants. In leaf disks excised from fully expanded leaves, transcript levels increased 25- to 35-fold within 24 h and by 48 h were reduced by about 50%. In flowering plants, message levels were 2- to 5-fold higher than in preflowering plants. These plants were used to test for defensive properties of cytokinins against insects. Manduca sexta larvae consumed up to 70% less of the PI-II-ipt leaf material on flowering plants than larvae feeding on controls. Normal development of Myzus persicae nymphs was also delayed. Approximately half as many nymphs reached adulthood on PI-II-ipt leaves than on controls. Zeatin and zeatinriboside levels in leaves remaining on PI-II-ipt plants after hornworm feeding were elevated by about 70 fold and the chlorophyll a/b content was double that of controls. Exogenous applications of zeatin to the PI-II-ipt leaves enhanced the level of resistance to the tobacco hornworm and almost completely inhibited normal development of the green peach aphid nymphs. Transcript levels of an acidic chitinase gene were low and minimally inducible in PI-II-ipt leaves. The mode of action of the cytokinin gene product on enhanced insect resistance is not clear but may involve the products of secondary metabolic pathways. PMID- 8219069 TI - DNA binding factor GT-2 from Arabidopsis. AB - Complementary DNA clones encoding a DNA-binding factor have been obtained from Arabidopsis by DNA hybridization with a GT-2 factor cDNA clone from rice. The GT 2 gene appears to be present as a single copy in the Arabidopsis genome and is transcribed as a 2.1 kb mRNA which is not light-regulated. The longest open reading frame in the sequenced clones predicts a protein of 65 kDa, beginning with the first in-frame methionine. The protein contains basic, acidic, and proline/glutamine-rich motifs and has significant amino acid sequence homology to the rice GT-2 factor, including three regions of 50-75 amino acids each of greater than 60% identity. Two of these regions are predicted to form similar trihelix structures postulated to be involved in selective binding to specific variations of a GT-box motif DNA sequence found in the promoter regions of several plant genes. Except for weak similarity to a tobacco GT-box binding factor, GT-1a/B2F, Arabidopsis GT-2 has no similarity to other sequences in the databases. DNA-binding studies show that Arabidopsis GT-2 has binding characteristics similar to those of the rice GT-2 factor, but dissimilar to those of the tobacco GT-1a/B2F factor. The data indicate that a DNA-binding factor containing domains of similar structure and target-sequence specificity has been conserved between monocots and dicots. PMID- 8219070 TI - Circadian and light-regulated expression of nitrate reductase in Arabidopsis. AB - The expression of a number of plant genes is regulated by an endogenous circadian clock. We report that the Arabidopsis NIA2 (nitrate reductase) gene shows robust circadian oscillations in mRNA accumulation which persist for at least 5 days in plants that have been grown in a light-dark (LD) cycle and then transformed to continuous light (LL). We further show that NIA2 mRNA accumulation oscillates in a circadian fashion in plants that have been grown in LD and then transferred to continuous darkness (DD). Results from nuclear run-on transcriptional analysis suggest that the oscillations in steady-state levels of NIA2 mRNA abundance are not primarily due to changes in transcription but, instead, reflect post transcriptional regulation. The circadian oscillations in NIA2 mRNA abundance are paralleled by circadian oscillations in nitrate reductase enzyme activity (NR activity) in Arabidopsis plants that have been grown in LD and then transferred either to DD or to LL. Etiolated Arabidopsis seedlings express neither NIA2 mRNA nor NR activity. However, both NIA2 mRNA accumulation and NR activity are induced by exposure to white light. The inductive effects of light on NIA2 mRNA accumulation are due, at least in part, to a very low fluence phytochrome mediated response. However, the persistence of circadian oscillations in NIA2 mRNA abundance for at least 5 days in LL demonstrates that the circadian clock is capable of overriding or gating the inductive effects of light on NIA2 mRNA accumulation in Arabidopsis for an extended, continuous period of time. PMID- 8219071 TI - Accumulation of type I fish antifreeze protein in transgenic tobacco is cold specific. AB - Expression of fish antifreeze protein (AFP) genes in plants is a possible means of increasing their frost resistance and freeze tolerance. Initial work involved transfer into tobacco of an AFP gene from winter flounder which codes for the alanine-rich, alpha-helical Type I AFP. Plants were transformed with a gene construct in which the preproAFP cDNA was inserted between the cauliflower mosaic virus 19S RNA promoter and the nopaline synthetase polyadenylation site. Although transgenic plants produced AFP mRNA, no AFP was detected on western blots. Re evaluation of AFP expression in these transgenic plants showed that AFP accumulated to detectable levels only after exposure of the plant to cold. Extracts of plants incubated at 4 degrees C for 24 h contained a protein which co migrated with winter flounder proAFP and was cross-reactive to Type I AFP antisera. Two other minor protein bands of slightly higher apparent M(r) also cross-reacted with the antisera and are thought to represent processing intermediates. The proAFP was unique to the transgenic plants and was absent in extracts taken prior to cold exposure. AFP levels increased over the first 48 h of cold incubation then remained stable. Since the alpha-helix content of Type I AFP has been shown to decrease markedly at warmer temperatures, we postulate that Type I AFP stability in transgenic plants is dependent on its secondary structure. PMID- 8219072 TI - Functional expression and molecular characterization of AtUBC2-1, a novel ubiquitin-conjugating enzyme (E2) from Arabidopsis thaliana. AB - The first member of a novel subfamily of ubiquitin-conjugating E2-proteins was cloned from a cDNA library of Arabidopsis thaliana. Genomic blots indicate that this gene family (AtUBC2) consists of two members and is distinct from AtUBC1, the only other E2 enzyme known from this species to date (M.L. Sullivan and R.D. Vierstra, Proc. Natl. Acad. Sci. USA 86 (1989) 9861-9865). The cDNA sequence of AtUBC2-1 extends over 794 bp which would encode a protein of 161 amino acids and a calculated molecular mass of 18.25 kDa. The protein encoded by AtUBC2-1 is shown to accept 125I-ubiquitin from wheat E1 enzymes, when expressed from Escherichia coli hosts as fusion protein carrying N-terminal extensions. It is deubiquitinated in the presence of lysine and, by these criteria, is considered a functional E2 enzyme. PMID- 8219073 TI - Identification of a defective transposable element in tobacco. AB - A putative defective transposable element has been identified in tobacco. This element has been found and characterised in two separate parts of the tobacco genome, specifically within the 3rd intron of the pollen-specific polygalacturonase gene (Npg1) and upstream of the endochitinase gene (Chn50). The element is ca. 0.4 kb in length and is bounded by conserved inverted repeats and putative target site duplications. It appears to fall into the category of non autonomous transposable elements. PMID- 8219074 TI - A rice (Oryza sativa L.) cDNA encodes a protein sequence homologous to the eukaryotic ribosomal 5S RNA-binding protein. AB - A rice (Oryza sativa L.) cDNA clone coding for the cytoplasmic ribosomal protein L5, which associates with 5 S rRNA for ribosome assembly, was cloned and its nucleotide sequence was determined. The primary structure of rice L5, deduced from the nucleotide sequence, contains 294 amino acids and has intriguing features some of which are also conserved in other eucaryotic homologues. These include: four clusters of basic amino acids, one of which may serve as a nucleolar localization signal; three repeated amino acid sequences; the conservation of glycine residues. This protein was identified as the nuclear encoded cytoplasmic ribosomal protein L5 of rice by sequence similarity to other eucaryotic ribosomal 5 S RNA-binding proteins of rat, chicken, Xenopus laevis, and Saccharomyces cerevisiae. Rice L5 shares 51 to 62% amino acid sequence identity with the homologues. A group of ribosomal proteins from archaebacteria including Methanococcus vanniellii L18 and Halobacterium cutirubrum L13, which are known to be associated with 5 S rRNA, also related to rice L5 and the other eucaryotic counterparts, suggesting an evolutionary relationship in these ribosomal 5 S RNA-binding proteins. PMID- 8219075 TI - Characterization of an Arabidopsis thaliana gene (TMKL1) encoding a putative transmembrane protein with an unusual kinase-like domain. AB - We have characterized a novel Arabidopsis gene, designated TMKL1 (for Transmembrane Kinase-Like). The encoded protein is predicted to contain an N terminal signal peptide, an extracellular domain with seven imperfect leucine rich repeats, a single hydrophobic transmembrane segment, and a kinase-like intracellular domain which lacks, however, several of the key conserved residues essential for catalytic activity. The TMKL1 protein thus represents a unique and functionally intriguing member of the family of plant proteins related to animal receptor kinases. Northern blot analysis indicates that the TMKL1 gene is transcriptionally active in a variety of organs, and is developmentally regulated during silique maturation. Its possible functions are discussed. PMID- 8219076 TI - Characterization of a birch (Betula pendula Roth.) embryogenic gene, BP8. AB - We have isolated the birch homologue (BP8) for the carrot embryogenic gene DC8 by heterologous hybridization. The birch BP8 gene encodes a putative protein of 53 kDa, showing 52% sequence identity with the DC8 gene at the amino acid level. The putative BP8 protein contains 20 repeats of 11 amino acids and thus belongs to the group of LEA proteins isolated from such plants as carrot, cotton and wheat. Northern hybridization of mRNA isolated from birch cells representing different stages of somatic embryogenesis and non-embryogenetic material with a PB8 probe gave no signals, suggesting a low expression level of the BP8 gene. PMID- 8219077 TI - Coordinate gene expression of five subclass histones and the putative transcription factors, HBP-1a and HBP-1b, of histone genes in wheat. AB - The expression of genes encoding five histones (H1, H2A, H2B, H3 and H4) and the putative transcription factors HBP-1a (17) and HBP-1b (c38) was examined during early germination and in various tissues of young wheat seedlings. The steady state levels of core histone (H2A, H2B, H3 and H4) mRNAs were coordinately cell cycle-dependent and paralleled the rate of DNA synthesis during early germination, whereas the expression pattern of the linker histone (H1) genes differed. The five subclass histone genes were actively expressed in the meristematic tissues of young seedlings. Moreover, H1 genes were expressed in leaves that consist mostly of non-proliferating cells, in which core histone genes showed little expression. Quantitative alterations to the mRNAs of the putative transcription factors HBP-1a (17) and HBP-1b (c38) of wheat histone genes were similar to those of the core histone mRNAs, suggesting that both factors function in the cell cycle-dependent expression of wheat core histone genes. PMID- 8219078 TI - A new middle repetitive sequence of Nicotiana plumbaginifolia genome. AB - A middle repetitive sequence NPR18 was isolated from Nicotiana plumbaginifolia nuclear genome [8]. Sequences homologous to the repeat are dispersed through genomes of several Nicotiana species. Computer-assisted data analysis of NPR18 primary sequence reveals several features attributed to mobile genetic elements: an AT content higher than average for nuclear DNA of genus Nicotiana plants; a number of direct and inverted repeats. Some of the repeats displayed homology to the terminal and subterminal repeats of Ac/Ds-like plant elements. PMID- 8219079 TI - A cDNA clone for a pathogenesis-related protein 1 from barley. AB - A barley cDNA clone (PRb-1) corresponding to an mRNA differentially induced in resistant compared to susceptible barley cultivars by powdery mildew infection was isolated and characterised. The deduced amino acid sequence revealed 24 amino acids comprising the signal peptide and 140 amino acids of the mature peptide (15 kDa). This showed close homology to PR-1-like proteins, which have been isolated from maize, tobacco, tomato and Arabidopsis thaliana. Northern blot analysis showed accumulation of the corresponding mRNA 12 h after inoculation of resistant barley cultivars with Erysiphe graminis. Increased expression of the PRb-1 gene was also observed in resistant compared with near-isogenic susceptible barley plants following treatment with ethylene, salicylic acid, methyl jasmonate and 2,6-dichloro-isonicotinic acid. PMID- 8219080 TI - Tobacco plants transformed with cdc25, a mitotic inducer gene from fission yeast. AB - We investigated the effects of expressing a cDNA of cdc25, a mitotic inducer gene of Schizosaccharomyces pombe, on the development of transgenic tobacco plants (Nicotiana tabacum cv. Samsun). Nine independent primary transformants were regenerated containing the cdc25 sequence under the control of a cauliflower mosaic virus 35S gene promoter. Eight of the nine plants showed altered leaf morphology, the lamina being lengthened and twisted and the interveinal regions being pocketed. One of these was sacrificed for analysis of the root meristem, where the cells were found to be significantly smaller than in the wild type. The other seven were grown on and showed precocious flowering, flowers being produced earlier and in significantly greater numbers than in the wild type. They also developed abnormal flowers on short stalks developing in a position normally occupied by the most proximal axillary bud of otherwise normal flower pedicels. The presence or absence of these phenotypes in the primary transformants and in the T2 generation was associated with the presence or absence of detectable levels of cdc25 transcripts. PMID- 8219081 TI - DNA-protein interactions on a cis-DNA element essential for ethylene regulation. AB - The PRB-1b gene encodes for a basic-type component of the pathogenesis-related PR 1 protein family. In leaves of tobacco plants, PRB-1b mRNA accumulation is rapidly induced by the application of exogenous ethylene. Promoter deletion analysis was performed in transgenic tobacco plants to delineate cis-acting elements necessary for ethylene responsiveness of the PRB-1b gene. The promoter sequence from position -213 was sufficient to enhance a 20 fold increase of beta glucuronidase reporter gene expression in transgenic tobacco leaves exposed to 20 microliters/l of ethylene, however -141 bp were not. The functional study was correlated with in vitro analysis of the nuclear protein-DNA complexes formed on the promoter element identified as necessary for ethylene induction. Gel-shift analysis using restriction fragments spanning the sequence between position -237 and -143 revealed two distinct nuclear protein-DNA interactions. The protein binding sequences were mapped to the contiguous regions G (-200 to -178) and Y ( 179 to -154) by gel-shift analysis using oligonucleotides. Fractionation of crude nuclear extract by heparin-agarose chromatography resulted in the differential elution of the two binding activities. The DNA-nuclear protein interactions characterized in vitro can be part of the molecular events which mediate the transcriptional regulation of the PRB-1b gene by ethylene. PMID- 8219082 TI - Construction of a Synechocystis PCC6803 mutant suitable for the study of variant hexadecameric ribulose bisphosphate carboxylase/oxygenase enzymes. AB - The cyanobacterium Synechocystis PCC6803 was chosen as a target organism for construction of a suitable photosynthetic host to enable selection of variant plant-like ribulose bisphosphate carboxylase/oxygenase (Rubisco) enzymes. The DNA region containing the operon encoding Rubisco (rbc) was cloned, sequenced and used for the construction of a transformation vector bearing flanking sequences to the rbc genes. This vector was utilized for the construction of a cyanobacterial rbc null mutant in which the entire sequence comprising both rbc genes, was replaced by the Rhodospirillum rubrum rbcL gene linked to a chloramphenicol resistance gene. Chloramphenicol-resistant colonies, Syn6803 delta rbc, were detected within 8 days when grown under 5% CO2 in air. These transformants were unable to grow in air (0.03% CO2). Analysis of their genome and Rubisco protein confirmed the site of the mutation at the rbc locus, and indicated that the mutation had segregated throughout all of the chromosome copies, consequently producing only the bacterial type of the enzyme. In addition, no carboxysome structures could be detected in the new mutant. Successful restoration of the wild-type rbc locus, using vectors bearing the rbc operon flanked by additional sequences at both termini, could only be achieved upon incubating the transformed cells under 5% CO2 in air prior to their transferring to air. The yield of restored transformants was proportionally related to the length of those sequences flanking the rbc operon which participate in the homologous recombination. The Syn6803 delta rbc mutant is amenable for the introduction of in vitro mutagenized rbc genes into the rbc locus, aiming at the genetic modification of the hexadecameric type Rubisco. PMID- 8219083 TI - Molecular characterization of a gene encoding a cysteine-rich protein preferentially expressed in anthers of Lycopersicon esculentum. AB - The tomato (Lycopersicon esculentum Mill.) cDNA clone TomA5B was isolated by differential screening of a cDNA library prepared from anthers at late meiosis to tetrad formation. The 5B gene is present in a single copy in the tomato genome. Expression is developmentally regulated and tissue specific. RNA accumulation was detected from premeiosis through tetrad release in the tapetal cell layer of the anther with low levels of RNA detected in petals and early stages of pistil development. The protein deduced from the DNA sequence analysis is predicted to have a molecular mass of 11.1 kDa and a secretory signal sequence, suggesting it is a secreted protein. The deduced 5B protein has a pattern of cysteine residues that is similar to other proteins that have stamen-specific expression and to a superfamily of seed proteins. The 5B protein is unique in that there is no amino acid sequence similarity to other proteins beyond the similar cysteine motif. PMID- 8219084 TI - Fruit developmental regulation of the kiwifruit actinidin promoter is conserved in transgenic petunia plants. AB - We have examined the expression of actinidin, a cysteine protease found in kiwifruit, over the course of fruit development. Protease activity was first seen in fruit that had reached about half their final weight, and rose to high levels at harvest. The 5'-flanking region (nucleotides -1301 to +58) of a kiwifruit actinidin gene was fused to the beta-glucuronidase (GUS)-coding region, and the chimaeric gene was introduced into transgenic petunia plants. Induction of the GUS gene was observed during the later stages of seed pod development, closely resembling the pattern of actinidin induction in fruit tissues of kiwifruit. Some GUS expression was also detected in the vascular system of the receptacle, leaves, stems and roots. A shorter promoter fragment consisting of nucleotides 115 to +58 conferred similar spatial and temporal regulation in some of the transgenic plants. PMID- 8219085 TI - Developmental and circadian pattern of rubisco activase mRNA accumulation in apple plants. AB - An apple cDNA encoding the precursor of ribulose 1,5-bisphosphate carboxylase/oxygenase (rubisco) activase has been characterized. Using this cDNA as a probe, leaf-specific and light-regulated accumulation of corresponding transcripts was detected. Rubisco activase transcripts also turned out to accumulate at growing levels during apple leaf development, to reach a maximum in fully expanded leaves. In contrast, chlorophyll a/b-binding protein (Cab) and rubisco large subunit mRNA levels reach a maximum earlier in the course of leaf development. Moreover, the accumulation of rubisco activase messengers appeared to follow an oscillating circadian rhythm qualitatively similar to that observed for Cab mRNA levels. PMID- 8219086 TI - The myrosinase (thioglucoside glucohydrolase) gene family in Brassicaceae. AB - The glucosinolate hydrolyzing enzymes myrosinase (thioglucoside glucohydrolase, EC 3.2.3.1) are encoded by a multigene family consisting of two subgroups. The first two nuclear genes representing each of these two subgroups of the new gene family, Myr1.Bn1 and Myr2.Bn1, from Brassica napus have been cloned and sequenced. Based on conserved regions in cDNA of three species, PCR (polymerase chain reaction) primers were made, and used to amplify and characterize the structure of the myrosinase genes in seven species of Brassicaceae. Southern hybridization analysis of PCR products and genomic DNA indicates that myrosinase is encoded by at least 14 genes in B. napus, with similar numbers in the other species of Brassicaceae investigated. The Myr1 gene cloned from B. napus has a 19 amino acid signal peptide and consists of 11 exons of sizes ranging from 54 to 256 bp and 10 introns of sizes from 75 to 229 bp. The Myr2 gene has a 20 amino acid signal peptide and consists of 12 exons ranging in size from 35 to 262 bp and 11 introns of sizes from 81 to 131 bp. The exons from the two genes have 83% homology at the amino acid level. The intron-exon splice sites are of GT..AG consensus type. The signal peptides and presence of sites for N-linked glycosylation, suggest transport and glycosylation through the ER-Golgi complex. The differences between the two genes are discussed on the basis of their predicted expression at different developmental stages in the plant. Both genes show homology to a conserved motif representing the glycosyl hydrolase family of enzymes. PMID- 8219087 TI - Prospects of applying a combination of DNA transposition and site-specific recombination in plants: a strategy for gene identification and cloning. AB - The concept of gene identification and cloning using insertional mutagenesis is well established. Many genes have been isolated using T-DNA transformation or transposable elements. Maize transposable elements have been introduced into heterologous plant species for tagging experiments. The behaviour of these elements in heterologous hosts shows many similarities with transposon behaviour in Zea mays. Site-specific recombination systems from lower organisms have also been shown to function efficiently in plant cells. Combining transposon and site specific recombination systems in plants would create the possibility to induce chromosomal deletions. This 'transposition-deletion' system could allow the screening of large segments of the genome for interesting genes and may also permit the cloning of the DNA corresponding to the deleted material by the same site-specific recombination reaction in vitro. This methodology may provide a unique means to construct libraries of large DNA clones derived from defined parts of the genome, the phenotypic contribution of which is displayed by the mutant carrying the deletion. PMID- 8219088 TI - Cloning of cDNA, expression, and chromosomal location of genes encoding the three types of subunits of the barley tetrameric inhibitor of insect alpha-amylase. AB - Three cDNA clones from barley developing endosperm, corresponding to proteins BTAI-CMa, BTAI-CMb and BTAI-CMd, which are the three types of subunits of the tetrameric inhibitor of insect alpha-amylases, have been identified and sequenced. The deduced amino acid sequence of BTAI-CMb corresponds to the CM16/CM17 type of subunit in wheat (92/90% identical residues) and has one putative N-glycosylation site (NLT) and a possible kinase-C phosphorylation site (SCR). The BTAI-CMa sequence differs at four amino acid residues from a previously reported one from cv. Bomi and the sequence deduced for BTAI-CMd completes (11 N-terminal residues) and confirms previously available data. The gene for BTAI-CMa (Iat1) is located in the beta arm of barley chromosome 7H (syn.1), while genes for both BTAI-CMb (Iat2) and BTAI-CMd (Iat3) are in the long arm of chromosome 4H. The three genes are expressed in endosperm and their mRNAs are not detected in the other tissues tested, except Iat1, which seems to be expressed at a low level in coleoptile and roots, where it is switched off by 50 microM methyl jasmonate. PMID- 8219089 TI - Isolation and characterization of a tobacco cDNA clone encoding a putative MAP kinase. AB - We have isolated and sequenced a MAP (mitogen-activated protein) kinase-type cDNA from a tobacco (Nicotiana tabacum L.) cell suspension cDNA library by screening with a PCR fragment amplified from the same library with oligonucleotide primers corresponding to two sequences conserved in yeast and animal MAP kinases. The tobacco sequence, ntf3, shows 45-54% identity to various members of the MAP kinase family at the protein level. Northern experiments showed that ntf3 is expressed in all tobacco tissues tested, including pollen isolated at different developmental stages. Southern analysis indicated that, as in other organisms, there is a family of MAP kinase genes in tobacco. In complementary tests, ntf3 could not substitute the yeast MAP kinase genes fus3 and kss1. PMID- 8219090 TI - Proximal promoter region of the wheat histone H3 gene confers S phase-specific gene expression in transformed rice cells. AB - The cis-regulatory elements that confer cell cycle-dependent expression to the wheat histone H3 gene were investigated in rice cells (Oc strain) transformed with H3/GUS chimeric genes. 5' deletion mutants of the H3 promoter region (from 1711, -908 or -185 to +57 relative to the transcription start site) were joined to the coding sequence of the bacterial beta-glucuronidase (GUS) gene then introduced stably into rice cells. S1 analyses of the RNA from transformed rice cells whose cell cycles had been synchronized by treatment with aphidicolin showed that the steady-state levels of the transcripts from chimeric genes were altered with the change in DNA synthesis and the content of rice H3 mRNA throughout the cell cycle. Even though H3 promoter activity decreased as 5' deletion proceeded, transcripts from the chimeric genes showed increases, as much as 10-fold 1 h after release from the aphidicolin block, which were rapidly lost over the next 4 h. The results suggest that the 242 bp sequence from -185 to +57, which contains the basal promoter region, confers the S phase-specific expression of the H3 gene and that the upstream sequence from position -186 is required for the full activity of this promoter. PMID- 8219091 TI - Activity of a maize ubiquitin promoter in transgenic rice. AB - We have used the maize ubiquitin 1 promoter, first exon and first intron (UBI) for rice (Oryza sativa L. cv. Taipei 309) transformation experiments and studied its expression in transgenic calli and plants. UBI directed significantly higher levels of transient gene expression than other promoter/intron combinations used for rice transformation. We exploited these high levels of expression to identify stable transformants obtained from callus-derived protoplasts co-transfected with two chimeric genes. The genes consisted of UBI fused to the coding regions of the uidA and bar marker genes (UBI:GUS and UBI:BAR). UBI:GUS expression increased in response to thermal stress in both transfected protoplasts and transgenic rice calli. Histochemical localization of GUS activity revealed that UBI was most active in rapidly dividing cells. This promoter is expressed in many, but not all, rice tissues and undergoes important changes in activity during the development of transgenic rice plants. PMID- 8219092 TI - Isolation, characterization and sequence of a cDNA encoding gamma-tubulin protein from the fern Anemia phyllitidis L. Sw. AB - A complete cDNA encoding gamma-tubulin protein from Anemia phyllitidis is presented. The deduced amino acid sequence shows an average similarity of 81-86% to known gamma-tubulin genes from insects, mammals and fungi. Northern blots indicate the existence of transcripts of ca. 1.9 kb which are expressed during gametogenesis of A. phyllitidis. The gene described is the first cloned and entirely sequenced gamma-tubulin gene in any plant. PMID- 8219093 TI - Activity of the promoter of the Lhca3.St.1 gene, encoding the potato apoprotein 2 of the light-harvesting complex of Photosystem I, in transgenic potato and tobacco plants. AB - We have isolated cDNA and genomic clones for the potato (Solanum tuberosum) apoprotein 2 of the light harvesting complex of Photosystem I, designated Lhca3.St.1. The protein shows all characteristics of the family of chlorophyll a/b-binding proteins. Potato Lhca3.1 gene expression occurs predominantly in leaves, and is transcriptionally regulated by light. One gene copy is present per haploid genome. The sequence of the 5' upstream region was determined. Most boxes identified in the promoter sequences of genes whose expression is light-regulated recur in the Lhca3.St.1 sequence. Functional analyses of the Lhca3.St.1 promoter and two deletion derivatives in transgenic potato transformed with a promoter-GUS fusion show high promoter activity in leaves and other green parts of the plant, which depends on light. Activity is absent in roots and potato tubers. The 500 bp promoter fragment is as active as the full 2.0 kb sequence, showing that all regulatory elements are present on the smallest deletion derivative. In transgenic tobacco (Nicotiana tabacum) plants carrying the largest promoter derivative a similar distribution of activity is found. Promoter activity is not restricted to the phloem, but also prominent in the xylem of the young stem, which contrasts with promoters of other photosynthesis-associated genes. PMID- 8219094 TI - Effects of promoter, intron and enhancer elements on transient gene expression in sugar-cane and carrot protoplasts. AB - Various chimaeric promoter regions coupled to the uidA beta-glucuronidase gene were evaluated for transient expression strength following electroporation into sugar-cane (monocot) and carrot (dicot) protoplasts. Multiple enhancer elements increased expression in sugar-cane, by up to 400-fold for the artificial Emu promoter relative to the CaMV 35S promoter. The relative expression strengths of promoters varied substantially between the species. Sugar-cane also differed in some respects from previously tested species in the family Poaceae. For example, in sugar-cane the nopaline synthase and CaMV 35S promoters were of equivalent strength, and insertion of Adh1 intron 1 into the 5' transcribed region decreased expression strength. PMID- 8219095 TI - Comparative analysis of chromosomal HMG proteins from monocotyledons and dicotyledons. AB - Chromosomal high-mobility-group (HMG) proteins occur ubiquitously in eukaryotes and their common structural and biochemical features indicate a critical role. In this context, we compared structural and functional aspects of HMG proteins from the monocotyledonous plant maize and the dicotyledonous plant Vicia faba. Besides biochemical similarities and immunological differences found between these proteins, the isolation and characterization of a cDNA encoding the V. faba homologue of the maize HMGa protein revealed great similarities between these two proteins, including the HMG-box DNA-binding motif and an acidic domain. Therefore, like the maize HMGa protein, the V. faba HMG protein belongs to the vertebrate HMG1 family, which consists of HMG proteins and transcription factors of various eukaryotes. PMID- 8219096 TI - A histidine decarboxylase-like mRNA is involved in tomato fruit ripening. AB - DNA sequencing of a tomato ripening-related cDNA, TOM 92, revealed an open reading frame with homology to several pyridoxal 5'-phosphate histidine decarboxylases, containing the conserved amino acid residues known to bind pyridoxal phosphate and alpha-fluoromethylhistidine, an inhibitor of enzyme activity. TOM 92 mRNA accumulated during early fruit ripening and then declined. Fruit of the ripening-impaired tomato mutant, ripening inhibitor (rin), did not accumulate TOM 92 mRNA, and its accumulation was not restored by treatment of fruit with ethylene. The TOM 92 mRNA was not detected in tomato leaves and unripe fruit. PMID- 8219097 TI - [Prognostic factors in typhoid perforation]. AB - This retrospective study evaluated 112 patients who had undergone surgery by typhoid perforation at the Belen Hospital, Trujillo, Peru, from 1967 trough 1990 in order to identify by univariate analysis the combination of factors predictive of postoperative morbidity and mortality. All the patients had one or more of the following diagnostic criteria: bacteriologic, serologic, anatomopathologic and surgical. The surgical procedures performed were: simple closure (n = 70), intestinal resection in conjunction with primary anastomosis (n = 6), intestinal resection plus ileostomy (n = 33), whilst peritoneal drainage operations were used in 3 cases. The following parameters were evaluated: age, sex, length of history, length of perforation, low intestinal hemorrhage, leukocyte count, type of peritoneal fluid and number of perforations. The operative mortality rate for all patients was 21.4% and morbidity rate was 80.4%. Significant differences in morbidity were only found in patients with perforations over 48 hours (p < 0.05). Analysis of post-operative mortality: length of perforation over 48 hours (p < 0.001), presence of hematochezia (p < 0.01), leukopenia (p < 0.05), fecaloid peritoneal fluid (p < 0.05) or the evidence of 3 or more intestinal perforations (p < 0.05). We concluded that a surgeon must take into account all of these factors to lead to satisfactory results. PMID- 8219098 TI - [Occupational exposure to hepatitis B virus in hospital personnel at the Naval Medical Center "Cirujano Mayor Santiago Tavara"]. AB - Four hundred apparently healthy workers from different service areas of the Naval Medical Center "Cirujano Mayor Santiago Tavara" constituted the basis for this epidemiological assessment for hepatitis B. Determination of serologic markers was done with an enzyme linked immunoabsorbent assay (ELISA). We evaluated hepatitis B surface antigen (HBsAg), total antibodies against hepatitis B core antigen IgG type (anti-HBc-IgG) and antibodies against hepatitis B core antigen IgM type (anti-HBc-IgM). Results showed that 11.75% of the samples studied had antibodies against the core antigen. Negative results were obtained for HBsAg and anti-HBc-IgM. We found correlation between blood contact and the prevalence of the total antibodies against hepatitis B core antigen IgG type in medical personnel. The total antibodies against hepatitis B core antigen IgG type was positive in function of previous history of hepatitis, time of occupation, and age. The results obtained in the present study confirm the increased risk of hepatitis B infection in health care personnel compared to general population. This seroepidemiological survey shows that hospital personnel of the Naval Medical Center has a lower prevalence of HBV infection that the prevalence found by other authors in the personnel of other hospitals in Peru. PMID- 8219099 TI - [Clinical and etiologic study of 90 cases of chronic diarrhea]. AB - 90 patients with chronic diarrhoea underwent this prospective study. They were seen in a private hospital of Lima during 1990 and 1991. According to a methodologic plan for determining sources and the diseases that originate chronic diarrhoea. In all patients hematologic, bioquimic, coprocultures, coproparasitologic exams were done, chest and intestinal transit X-rays. All underwent duodenal content culture. Colon X-ray in 25 cases; proctosigmoidoscopy in 14 and upper digestive endoscopy in 19 patients. Abdominal echography in 12 and TAC in 2 cases. The final results showed as determinant diseases for chronic diarrhoea, according to their frequency: enteroparasitosis (23.3%), functional digestive disorders (20.0%), intestinal bacterial overpopulation (15.5%) of unknown origin (8.8%), colon diverticulus (7.7%) proven and probably (5.5%), lactose intolerance (3.3%), diabetes mellitus (2.2%), and in one case (1.1%) the following: intestinal linfoma, pancreas malignancy, AIDS, colonic and deformation and megaloblastic anemia. The causes of chronic diarrhoea are several and multifactorals and in this study we prove the preeminence of the intestinal parasitosis, functional disorders and intestinal bacterial overpopulation and with less frequency other pathologies. PMID- 8219100 TI - [Operative mortality in sigmoid volvulus]. AB - This retrospective analysis evaluated 123 patients with sigmoid volvulus that underwent surgery at the Belen Hospital, Trujillo, Peru, from January 1, 1967 to December 31, 1992 in an attempt to identify by univariate analysis factors of prognostic value of operative mortality. The surgical procedures performed were destortion plus colopexia (n = 19), intestinal resection with primary anastomosis (n = 69) and resection plus colostomy (n = 35) with an operative death rate of 0%, 13% and 31.4% respectively (p = 0.005). The overall operative mortality rate was of 19.4%. The following parameters were evaluated: age, sex, duration of obstruction, mean arterial pressure, leukocyte count, type of peritoneal fluid, state of the bowel and surgical technique. Analysis of post-operative mortality disclosed the following factors associated with increased mortality: age older than 40 (p = 0.008), mean arterial pressure lower than 70 mmHg (p = 0.0001), presence of purulent or fecaloid peritoneal fluid (p = 0.001) and evidence of gangrenous colon with perforation (p = 0.0001). There were no statistically significant differences in mortality rate with regard to sex, length of history and leukocyte count. Therefore, we emphasize the need to take into account these risk factors to better clarify appropriate therapy options. PMID- 8219101 TI - [Intestinal parasitosis: physiopathologic aspects]. AB - The variety of pathological changes that occur during parasitic infections is diverse. Recently there has been done considerable progress in understanding the physiopathologic aspects of the direct parasitic action of the products that they release, that affect the digestive function. The pathogenetic effects of intestinal parasites are important, not only for the adult forms that occupy the lumen or the intestinal mucosa, but for the migratory forms. The most important clinical manifestations are in direct relation with the host response to the aggression or trauma caused by the migratory larvae and/or adults parasites, the signs and symptoms depends on the infestation phase and on the severity or in the agent "virulence". The objective of this article is to present a brief revision on the physiopathologic effects of infestations by intestinal parasites. PMID- 8219102 TI - [Chylous ascites: report of a case and review of the literature]. AB - A patient presenting chylous ascitis due to an epithelial originated malignancy is reported. The primary focus of the malignancy could not be precise in spite of all diagnoses procedures available including explorer laparatomy. As this is a very unusual occurrence in the clinical practice, a review of reported literature has been made on ethological, physiopathological and therapeutical aspects. PMID- 8219103 TI - Regulatory mechanisms underlying T cell integrin receptor function. AB - Adhesion molecules allow lymphocytes to interact with and respond to the extracellular environment. Since these interactions must be essentially transient in nature, the function of lymphocyte adhesion molecules must be precisely regulated. Studies of integrin receptors vividly illustrate the various mechanisms by which the function of these adhesion molecules can be regulated. These include: (1) activation-dependent changes in functional activity; (2) changes in levels of expression due to differentiation events; (3) cell-specific differences in integrin binding; and (4) differential binding to distinct ligands by the same integrin. These mechanisms provide highly precise and specific modes of regulating lymphocyte interactions with a wide variety of potential counter receptors and ligands. PMID- 8219104 TI - CD8 and antigen-specific T cell adhesion cascades. AB - Activation of T cells involves both the antigen-specific T cell receptor and a number of additional accessory receptors. For cytotoxic T lymphocytes these include CD8, LFA-1 and VLA receptors. Recent studies have demonstrated that these receptors become activated to mediate adhesion upon crosslinking of the T cell receptor, and can deliver co-stimulatory signals upon binding their ligands. Rather than being redundant adhesion/co-signalling systems, these various receptors participate in a cascade of adhesion and signalling events leading to full activation of cellular responses. PMID- 8219105 TI - T cell adhesion to endothelium: the FRC conduit system and other anatomic and molecular features which facilitate the adhesion cascade in lymph node. AB - Since T cell surveillance depends on movement from blood into tissue and back again, rapid, efficient and selective T cell adhesion to vascular endothelium is essential. This adhesion involves a multistep cascade clarified by a recent consensus model: (1) initial tethering by selectin-mediated interactions; (2) triggering of adhesive function of T cell integrins by ligands at or near the endothelial surface; and (3) strong adhesion mediated by T cell integrins. We recapitulate this model, particularly as it pertains to the lymph node, and explore additional molecular and anatomic elements which contribute to the effectiveness of the adhesion cascades at that site: (1) importance of cytokines/soluble mediators as triggering ligands; (2) role of glycocalyx and proteoglycans on high endothelial venule (HEV) endothelium in capturing and presenting triggering cytokines; (3) remarkable function of what we designate the 'fibroblastic reticular cell (FRC) conduit system' in rapidly transporting cytokines to the HEV; (4) importance of the unique anatomy of the flap-valve junctions between HEV endothelium in enabling intravasation of cytokines and transmigration of lymphocytes. Taken together, these molecular mechanisms and these three anatomic features of lymph node facilitate extremely efficient lymphocyte traffic to this site critical for T cell-mediated immune responses. Analogous mechanisms contribute to T cell interaction with endothelium at other sites. PMID- 8219106 TI - Long-term time-lapse cinemicrography of human erythroblasts under compression and without compression--direct measurement of generation time of each maturation stage. AB - The in vitro proliferation and the successive morphological alterations of single human erythroblasts were recorded for 5 days by time-lapse, phase-contrast cinemicrography. To visualize their fine structures more clearly, we introduced a new device to compress the erythroblasts under a cover slide. Appropriate compression did not significantly affect the capacity of the erythroblasts to proliferate and differentiate, although compression produced a slight tendency towards shorter generation time. The directly measured generation time was 24.5 +/- 4.5 h (mean +/- S.D.) for generation -1 (one generation prior to the orthochromatic erythroblast stage); 18.4 +/- 3.0 h for generation -2; and 18.3 +/ 4.1 h for generation -3 [corrected], these being arranged in inverse order of cell lineage. The cell size became progressively smaller and the nucleus-to cytoplasm ratio decreased along with the maturation of the erythroblasts, showing a distinctive distribution range for each generation. Progression of hemoglobinization was simultaneously recorded qualitatively by Soret band absorption micrography. Cell movements characteristic for each maturation stage, e.g. perimitotic bleb-throwing of immature erythroblasts and vigorous movements of orthochromatic erythroblasts, heralding enucleation, were also clearly recorded. The method described here will be useful for the direct study of the dynamic morphology of the erythron in normal and abnormal states. PMID- 8219107 TI - A patient with Tn syndrome associated with myelodysplastic syndrome showed abnormal glycophorin B. AB - A Japanese male patient with myelodysplastic syndrome (MDS) was shown to have associated Tn syndrome; the first report of Tn syndrome with MDS. The Tn expression was demonstrated on erythrocytes, granulocytes, monocytes, platelets, and lymphocytes by flow cytometric analysis using a lectin and an antibody. Electrophoresis of erythrocyte membrane proteins revealed slower mobility of glycophorin B from the patient than that from normal individuals, suggesting a glycophorin B molecular abnormality. PMID- 8219108 TI - Brain granulocytic sarcoma at the site of previous cerebral hemorrhage in a patient with acute myelogenous leukemia. AB - An unusual case of granulocytic sarcoma developing at the site of a previous cerebral hemorrhage in a patient with acute myelogenous leukemia in complete hematological remission is presented. The pathogenesis of the tumor growth at this site and its relevance to the antecedent hemorrhage are discussed. PMID- 8219109 TI - Interplay between differentiation and cell cycle arrest at G1 in phorbol diester treated human myelocytic leukemia cells. AB - The cell cycle arrest at G1 of myelocytic leukemia cells by incubation with phorbol diesters was examined in HL-60 cells and more mature THP-1 cells. We found: (1) induction of phenotypic parameters of differentiation prior to G1 arrest; (2) a long induction period in HL-60 cells compared to zero in THP-1 cells; and (3) strong inhibition of G1 arrest with a protein kinase C inhibitor in THP-1 cells. We conclude, from these lines of evidence and some additional information, that differentiation induces G1 arrest. At present, the most plausible causative molecule is Mac-1. PMID- 8219110 TI - Okadaic acid biologically mimics the role of calcium/phospholipid dependent kinase inhibitors in the process of HL-60 cell differentiation. AB - Okadaic acid, a newly recognized protein phosphatase inhibitor and a non-TPA type tumor promoter, enhanced 1 alpha 25(OH)2D3(D3)-induced HL-60 cell differentiation into monocyte/macrophage lineage but did not affect dibutyryl cyclic AMP (dbcAMP) induced differentiation into granulocytic lineage. Okadaic acid alone did not induce any differentiation. The process of D3-induced HL-60 cell differentiation on cultivation in magnesium deficient medium can be divided into two steps namely commitment and phenotypic expression as we have previously reported (J Cell Physiol 1987;131:50; Cell Growth Diff 1991;2:415), and the effect of okadaic acid on each step was studied. The results obtained indicated that okadaic acid inhibited commitment and enhanced phenotypic expression. We have previously shown that PKC has a dual action in the process of differentiation, i.e. as a positive regulatory signal in commitment and as a negative one in phenotypic expression. Thus, although okadaic acid has been reported to enhance the phosphorylation of various proteins that are also phosphorylated by PKC, we found that it mimics the role of PKC inhibitors such as H7 and staurosporine in D3-induced HL-60 cell differentiation. PMID- 8219111 TI - Enhancing effects of IL-2 on M-CSF production by human peripheral blood monocytes. AB - Monocytes have the capacity to produce granulopoietic factors such as M-CSF and G CSF. Our findings here showed that interleukin-2 (IL-2), at a concentration of more than 0.05 ng/ml, led to a 12-fold increase in the production of M-CSF in the human peripheral blood mononuclear cells after 72 h incubation compared to the control culture. Even in purified monocyte cultures with added IL-2, a 3-fold increase in M-CSF production was observed at an IL-2 concentration of 50 ng/ml. The enhancing effect of IL-2 on M-CSF secretion was also observed when IL-2 stimulated non-phagocytic cell-conditioned medium was added to monocyte cultures. These results indicated that IL-2, both directly and indirectly, activated monocytes to enhance the production of M-CSF. In addition, the expression of IL-2 receptor (CD25) on monocytes was more enhanced in cultures containing IL-2 than in cultures without IL-2. On the other hand, IL-2 did not induce G-CSF production in purified monocytes. These in vitro results suggest that when IL-2 is used clinically, the various biological activities of M-CSF should also be taken into consideration. PMID- 8219112 TI - Clinical and cytogenetic findings of myelodysplastic syndromes showing hypocellular bone marrow or minimal dysplasia, in comparison with typical myelodysplastic syndromes. AB - Hematologic and cytogenetic data were collected on 401 myelodysplastic syndromes (MDS) patients in Japan and their clinical relevance was analyzed. More than 50% of the MDS patients with hypocellular bone marrow had > 5% marrow blasts at the time of MDS diagnosis and frequently had complex aberrations (chromosome changes at three or more regions). They showed peripheral blood findings resembling those of aplastic anemia, but progression into leukemic phase and the prognosis tended to mimic typical MDS. In MDS patients with minimal dysplasia, hematologic parameters were different from those of aplastic anemia. However, the low incidence of leukemic transformation and the favorable prognosis was similar to that of aplastic anemia. More than 90% of the patients in this group had refractory anemia and had normal karyotypes. Thus differential diagnosis from a low grade aplastic anemia is important, since this type of MDS might have a clonal nature as well. In conclusion, although some hematologic and clinical deviations are noticed in MDS with hypocellular marrow or minimal dysplasia, these MDS subtypes might constitute marginal forms of MDS. PMID- 8219113 TI - Single daily ceftriaxone and tobramycin in the empirical management of febrile neutropenic patients: a randomised trial. AB - A single-institution, randomised pilot trial was conducted to compare the clinical efficacy, microbiological efficacy and possible toxicity of empirical single daily antibiotic administration in febrile neutropenic patients with haematologic disorders (absolute neutrophil count < 1 x 10(9)/l). Upon the development of signs of sepsis, patients received either single daily dose tobramycin (5 mg/kg per day) plus ceftriaxone (2 g/day) (C + T, n = 47) or tobramycin (1.5 mg/kg, every 8 h) plus azlocillin (4 g, every 6 h) (A + T, n = 45). In addition, flucloxacillin (1-2 g, every 4 h) could be added if there was clinical suspicion of staphylococcal infection (17 in each arm). Analysis was performed for the whole group and for the subset which did not receive flucloxacillin. When evaluated at 96 h, 62% of patients randomised to C + T and 67% randomised to A + T had responded (95% confidence interval (CI) for the difference in rates, -25% to +15%). Ninety-six hour response rates for those who did not receive flucloxacillin were 73% and 78%, respectively (95% CI, -17% to +27%). Overall, 42 (89%) and 41 (91%) patients, respectively, eventually became afebrile (95% CI, -14 to 10%) and there was no evidence of altered renal function or electrolyte imbalance in patients randomised to single daily antibiotic therapy compared with the conventional (multi-daily dose) arm. Within 10 days of antibiotic commencement there was 1 death in the C + T arm and 4 deaths in the A + T arm, although overall there were 4 deaths in each arm. Our results suggest that single daily empirical antibiotic therapy with tobramycin and ceftriaxone is efficacious and is not associated with an increased incidence of renal dysfunction or electrolyte imbalance compared with conventional administration schedules of azlocillin plus tobramycin. Single daily therapy has the potential to lead to savings in nursing-staff time and materials and may well contribute to an improved quality of life for febrile neutropenic patients. PMID- 8219114 TI - Interleukin-2 prevents programmed cell death in chronic lymphocytic leukemia cells. AB - When B-cell chronic lymphocytic leukemia (B-CLL) cells derived from peripheral blood are cultured in vitro, a substantial proportion die spontaneously by programmed cell death (PCD). In this study, we reexamined this phenomenon with both B-CLL and T-CLL cells, using a serum-free culture system. After 48 h of culture, in B-CLL cells, 23.3% +/- 6.7% (mean +/- S.E.M., n = 3) of total DNA was fragmented, while in 2 cases of T-CLL, this value was 32% and 45%, respectively. Analysis by electrophoresis indicated that the DNA of the B-CLL and T-CLL cells had been cleaved into regular oligonucleosome fragments comprising approximately 180-200 base pairs. This process was significantly promoted by methylprednisolone and the protein kinase A (PKA) activator Sp-cAMPS in at least some cases. Since B CLL and T-CLL cells often possess interleukin-2 (IL-2) receptors on their cell membranes, we assessed the effects of IL-2 on spontaneous PCD. After a 48-h culture PCD was inhibited by 100 units/ml IL-2 by 31.7% +/- 6.6% in B-CLL (n = 3) and by 47% in one of 2 cases of T-CLL. This protective effect of IL-2 against spontaneous PCD was dose- and time-dependent. These findings suggest that the viability of B-CLL and T-CLL cells in vivo is regulated both positively and negatively by intrinsic IL-2, glucocorticoids, and regulators of PKA activity. This process of cell death may be involved in the development of CLL. PMID- 8219115 TI - Hematology and erythrocyte biochemistry of spectacled hare-wallaby, Lagorchestes conspicillatus (Macropodidae Marsupialia). AB - Hematology and the red cell enzymes, metabolites, and rates of lactate production were measured in a small marsupial, the spectacled hare-wallaby Lagorchestes conspicillatus. In common with other marsupials of similar body weights, the red cells of this wallaby were found to have low levels of ATP and higher levels of 2,3-diphosphoglycerate (DPG) and produced no lactate when incubated with inosine. One of the five animals examined was suffering from anemia (hematocrit of 22.0% and hemoglobin concentration of 7.2 g/dl compared with the normal values of 46.6% and 15.8 g/dl, respectively); its red cells had almost twice the concentrations of ATP and DPG and had significantly higher activities of several enzymes of the glycolytic pathway. PMID- 8219116 TI - [Initial findings using dynamic magnetic resonance tomography in the diagnosis of inflammatory diseases of the sacroiliac joint]. AB - Up to now 42 patients with clinically suspected diagnosis of sacroiliitis (including 19 patients with confirmed spondylitis ankylosans) and 12 healthy volunteers were examined via magnetic resonance tomography. In oblique sections parallel to the plane of the sacrum the signal intensity patterns from normal and pathological tissues of the sacroiliac articulations were evaluated by plain T1 weighted spin-echo sequences and T2*-weighted FLASH sequences. In addition we used a dynamic FLASH measurement following intravenous application of gadolinium DTPA for quantitative calculation of signal-time courses. This method has proved to be capable of definitely differentiating normal findings of sacroiliac articulations from inflammatory changes (p = 0.0001) and also enables quantification of the inflammatory activity. PMID- 8219117 TI - [Special MR methods for primary bone tumors: II. Volume selective 1H spectroscopy]. AB - The method of localised 1H MR spectroscopy was used in 19 examinations in 9 patients with primary bone tumours in order to obtain spectral signals and to determine whether these are specific for tumour classification. The spectra were obtained by a double spin echo method and the tumour tissue showed very high water content and only minor lipid and proton signals which showed J-coupling characteristics. The latter are not found in normal bone marrow and are probably due to products of tumour metabolism. The resolution of the spectra within a 13 mm or 20 mm tissue cube depends largely on the structural homogeneity of the tumour. The signal patterns in the spectra were not specific to histological tumour types. PMID- 8219118 TI - [Localization dependent patterns of findings in chondroblastoma]. AB - In a retrospective study the radiographs of 48 chondroblastomas from the files of the Bone Tumour Registry of Westphalia were evaluated. The purpose of the study was to investigate whether chondroblastomas display localisation-dependent radiographic patterns. All radiographs were analysed using the Lodwick criteria. All chondroblastomas (mean age: 18 y., m:f = 1.25:1) showed a geographic pattern of bone destruction. 32 lesions affected long bones, 10 short bones, and 6 flat bones. Chondroblastomas localised in flat bones (Lodwick IA: 0%, IB: 33%, IC: 67%) demonstrated more aggressive patterns of bone destruction compared to lesions affecting long bones (Lodwick IA: 56%, IB: 31%, IC: 13%) or short bones (Lodwick IA: 40%, IB: 50%, IC: 10%). There was no difference between the three bone types in other radiographic patterns (periostitis, calcification, trabeculation). PMID- 8219119 TI - [A structural parameter for characterizing early trabecular changes in the spine in osteoporosis]. AB - The pattern of the spongiosa in lumbar vertebrae demonstrated by ultra high resolution CT was treated statistically. Comparison of normals with osteoporotic vertebrae showed no significant difference in the large dominant trabeculae. However, there is a significant difference when quantifying the fine structures which are not to resolve lying between the larger trabeculae. PMID- 8219120 TI - [Native radiologic staging of osteoporosis--CT densitometry of lumbar vertebral spongiosa. A correlation study]. AB - Lumbar spine radiographs in 47 patients with manifest or clinically suspected osteoporosis were evaluated, using a staging system, and correlated to quantitative computed tomography (QCT) of lumbar vertebrae. The accuracy of osteoporosis assessment, obtained with plain film analysis, was 60%, the sensitivity 67%, the specificity 56%. Statistical correlation showed high standard deviation of each of the QCT-mean values according to the respective stage groups, and altogether poor linear correlation between increasing morphological stages of osteoporosis and decreasing QCT-values. As our results show plain film differentiation of normal from reduced trabecular bone mineral content is unreliable, even by use of a staging system. The diagnostic value of spine radiographs therefore remains limited to demonstration of advanced osteoporotic changes. PMID- 8219121 TI - [MRT in the diagnosis of mandibular osteomyelitis following radiotherapy]. AB - A prospective study was performed to assess the diagnostic potential of MRI in mandibular osteomyelitis after radiation therapy. A total of 60 MRI studies were performed in 39 patients with lymphoma and carcinoma of the head and neck. Clinically or histologically proven osteomyelitis of the mandible occurred in 10 patients depending on the radiation dose absorbed to bone; 9 of these were unequivocally diagnosed by typical MRI appearance, two cases were false positive. MRI is superior to other diagnostic methods such as conventional radiology and clinical examination. It should be performed routinely in an oncological follow up after radiation therapy depending on the dental status and radiation dose. PMID- 8219122 TI - [The value of high resolution computed tomography (HRCT) in the diagnosis of deep forms of parodontitis]. AB - It is difficult to demonstrate the extent of parodontal bone erosions with conventional radiographic techniques. HRCT makes it possible to demonstrate the alveolar structures without superimposition. 10 patients with parodontitis marginalis profunda were examined by conventional methods and HRCT. Comparison showed considerable superiority of HRCT in respect of demonstrating bone destruction. The absence of superimposition produces excellent demonstration of the roots and shows the bifurcation and trifurcation of teeth; consequently, mapping the position and shape of the root canals is possible and this is an important aid in the planning of parodontal surgical treatment. PMID- 8219123 TI - [Carbon monoxide poisoning: the importance of computed and magnetic resonance tomographic cranial findings for the clinical picture and follow-up]. AB - Clinical, CT and MR imaging findings of 5 patients are presented who suffered from sudden coma due to carbon monoxide intoxication. Follow-up investigations were done for up to three years. 4 patients recovered with only minor deficits, while one patient survived with a severe choreatic syndrome. Cranial computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated typical lesions in the globus pallidus, the cerebral white matter and the cortex. Initial lesions of the cerebral white matter rather than of the globus pallidus seem to indicate a doubtful clinical prognosis. In the CT of the severe case progressive white matter atrophy was visible still after half a year. In contrast, in two cases with good outcome repeated MRI showed no progressive white matter changes. PMID- 8219124 TI - [Quantification of extracranial carotid stenosis. Magnetic resonance angiography and Doppler sonography versus intra-arterial angiography]. AB - To assess various non-invasive techniques for quantifying internal carotid artery CA stenosis, per cent luminal diameter reduction on intraarterial angiograms (IAA) was measured in 63 patients with ICA stenosis or occlusion. These data were compared with independent measurements based on MR-angiography, continuous-wave (cw) Doppler ultrasonography, systolic peak flow velocity and colour Doppler assisted duplex imaging. Correlations with IAA were equally strong for MR angiography, cw Doppler and colour Doppler analysis (0.95; 0.92; 0.92). Positive predictive values for > or = 70% ICA stenosis were lower and negative predictive values were higher for cw Doppler (0.85; 0.92) and colour duplex analysis (0.81; 0.94) than for MR angiography (0.86; 0.88). Statistical analysis showed non linear correlations between percentage of lumen diameter narrowing and the length of the zone of signal intensity loss (0.72) and maximum systolic peak flow velocity (0.77). CONCLUSION: Several non-invasive methods do compare with IAA in identifying and quantifying high-grade ICA stenosis and may suffice for decisions on treatment. PMID- 8219125 TI - [Interobserver variability of dialysis shunt flow measurements using color coated duplex sonography]. AB - A prospective study extending over 4 months was carried out in which 142 shunt volume flow measurements were performed on 43 patients; two up to four operators with varying degrees of experience took part. Flow volumes varied between 51 and 2409 ml/min with an average blood flow volume of 521 ml/min. Comparison of measurements of individual operators showed errors of between 0.5 and 19.8%. Average error was calculated as 11.3%. Shunt flow measurements by colour Doppler sonography provide an easily appreciated and reproducible method for quantifying changes in shunt flow. PMID- 8219127 TI - [Initial experiences with the MR "magnitude contrast angiography of the lower extremities]. AB - 45 patients with occlusive peripheral vascular disease were examined by MR angiography in a retrospective study. A FISP 3D sequence was used by acquiring a rephased and a dephased data set. The individual slices were post-processed by using a maximum-intensity-projection algorithm. The MRA results of the popliteal and tibioperoneal arteries were compared to conventional or digital angiography. In comparing these techniques MR angiography cannot be accepted for pre- and postoperative staging of patients with occlusive peripheral vascular disease. In future new MRA techniques may be useful in postoperative staging of patients with peripheral vascular stenosis. PMID- 8219126 TI - [The role of embolization treatment of acute hemorrhage]. AB - 137 arteries of 95 patients were treated by transcatheter embolization for massive haemorrhage using Ethibloc, Gelfoam, wire coils and Tissucol (Fibrinogen + Thrombin). The bleeding was secondary to trauma in 23 patients, to neoplasms in 16 patients and to vascular malformations or chronic inflammatory processes in 41 cases. 15 patients were treated for iatrogenic bleeding following surgery. Bleeding was referred to haemoptysis (n = 27), pelvic (n = 24), renal (n = 16) or gastrointestinal haemorrhage (n = 13) as well as several other diseases (n = 15). Most patients were poor surgical candidates. The overall bleeding control rate was 89.5% with a incidence of recurrent bleeding in 14 out of 95 patients (14.7%) treated by re-embolization or surgery. 6 patients died (6.3%) due to intractable haemorrhage, 4 patients (4.2%) died of complications related to embolization procedure (4 x bowel infarction!) and 33 patients (34.7%) died of procedure unrelated causes such as myocardial infarction, trauma, malignancy or other underlying diseases. 58 patients (61.1%) are still alive (follow-up 16.2 +/- 4.8 months). Significant complications (5.3%) included bowel necrosis (4x) and ischaemia of the spinal cord with incomplete paralysis in one patient. One patient suffered thrombosis of the common iliac artery due to angiography. On the basis of our results, peripheral embolization using Ethibloc can be recommended as palliative treatment for devascularisation of bleeding tumours. Satisfactory results are obtained in haemoptysis, renal and pelvic haemorrhage, but gastrointestinal bleeding should not be occluded by means of Ethibloc because of its considerable risk of bowel infarction. PMID- 8219128 TI - [The isolated fracture of the hamulus ossis hamati--an easily overlooked wrist injury]. PMID- 8219129 TI - [Cavernous hemangioma of the mediastinum]. PMID- 8219130 TI - Micronodular focal fatty infiltration of the liver. PMID- 8219131 TI - [Magnetic resonance tomography of focal fatty liver using separate fat-water imaging]. PMID- 8219132 TI - [Screening for breast carcinoma. The need, benefit and risks]. PMID- 8219133 TI - [31P-MR spectroscopy of liver diseases with reference to variable pulse recovery times]. AB - The value of 31P-MRS for different types of liver disease and the effect of repetition time (TR) on measurements of relative phosphor metabolite concentrations was studied. Spectroscopy was performed on 26 patients with predominantly focal liver disease and on 14 normals, using a 1.5 Tesla clinical MR system. In all cases, (TR) of 2,400 ms was chosen and in 11 patients and 10 normals additionally shorter (TR) of 600 ms (with T1 weighted spectra) was chosen. The results show that PME/beta-ATP and PDE/beta-ATP are sensitive indicators of liver disease and differ widely from the findings in normal livers. In patients with liver metastases, the long (TR) of 2,400 ms (16 cases) showed an increase of PME/beta-ATP (0.96 +/- 0.32) and significant reduction of PDE/beta ATP (1.89 +/- 0.47) as compared with normals (PME/beta-ATP = 0.75 +/- 0.26 and PDE/beta-ATP = 2.27 +/- 0.41), for a (TR) of 600 ms, PME/beta-ATP (0.87 +/- 0.47) and PDE/beta-ATP (1.82 +/- 0.67) are significantly increased. T1 weighted spectra showed more significant differences in phosphometabolites between patients and normals than density weighted spectra. The spectra in patients showed a significantly reduced signal to noise ratio independent of the (TR). PMID- 8219134 TI - [Metabolic studies of the calf musculature with 31P-MR spectroscopy in arterial obstructive disease before and after lumbar sympatholysis]. AB - In 9 patients with arterial occlusive disease of grade IV according to Fontaine, energy metabolism was measured in the calf muscle during rest, before and after lumbar sympatholysis, by means of 31phosphorus MR spectroscopy. The concentration of inorganic phosphate (Pi) and phosphocreatine (PCr) relative to high energy phosphates, as well as the pH value in muscle cells were assessed, and the quotient Pi/PCr was calculated for estimation of energy reserves. Before sympatholysis, normal concentrations of the energy suppliers ATP and PCr were unexpectedly found in combination with reduced cellular energy reserves. After lumbar sympatholysis, in most cases no significant changes of muscle energy metabolism were detected. Independent of the muscle energy supply, a slight increase in energy supply without returning to normal values was found in only three patients. In most patients the clinical symptoms had improved at least to some extent. PMID- 8219135 TI - [MR tomographic measurement of the diastolic relaxation of the hypertrophied left ventricle with the single-slice-multiphase technic]. AB - In order to assess diastolic ventricular function in hypertensive patients, a single-slice multiphase sequence was used in order to measure contraction and early diastolic relaxation. There was no difference in the contraction velocity between hypertensives and normals (Vsys. n.r. = 56.1 +/- 13.8% LVDV/s vs. 51.7 +/ 8.6% LVEDV/s, stat, n. sign.). Early diastolic relaxation velocity in hypertensives was reduced as compared with the control group (Vdiast. 1n.r. = 37.9 +/- 13.1% LVEDV/s vs. 47.1 +/- 9.6% LVEDV/s, p < 0.05). There was no linear relation between abnormal relaxation and the extent of myocardial hypertrophy. Hypertensives with myocardial hypertrophy frequently had reduced early diastolic relaxation velocity. Regression analysis for estimating left ventricular volumes derived from single-slice measurements were confirmed by additional multislice measurements. The calculated LVEDV correlated at r = 0.956 with multi-slice measurements and tended to show lower values (LVEDV n.r. = 104.6 +/- 30.8 ml vs. LVEDV = 102.1 +/- 28.8 ml, r = 0.956, p < 0.05). The LVESV was overestimated by the multi-slice technique, the calculated regression volume averaged 23% lower, realistic values (LVESV n.r. = 28.5 +/- 15.3 ml vs. LVESV = 37.1 +/- 15.6 ml, r = 0.887, p < 0.001). PMID- 8219136 TI - [The value of the AMBER system in demonstrating intrathoracic space-occupying lesions. A comparative ROC study of the AMBER and conventional technics for postero-anterior views of the thorax. Advanced Multiple Beam Equalization Radiography]. AB - Since October 1991 the AMBER technique has been used for the diagnosis of chest diseases in about 4,000 patients. The ability of this technique, compared with conventional methods, for demonstrating intrathoracic masses on p.a. views has been assessed. Amongst the patients there were 43 with coin lesions, 18 with hilar and 33 with mediastinal masses. ROC analysis showed the AMBER technique to be superior in demonstrating coin lesions (AMBER 0.92, conventional 0.85) and mediastinal masses (AMBER 0.89, conventional 0.73). There was a small, statistically not significant, disadvantage in the AMBER technique for demonstrating hilar masses (AMBER 0.80, conventional 0.84). PMID- 8219137 TI - Radiological aspects of hard metal disease. AB - The results of 30 years screening of exposed workers in the hard metal industry are presented in a retrospective study. There were 11 workers who had radiographic signs of pulmonary fibrosis. No correlation was found between intensity and/or duration of exposure and the stage and progression of pulmonary fibrosis. In 45% of the cases there was progression of the fibrosis after cessation of the exposure. Steroid therapy in three cases relieved the subjective symptoms but there was no regression of the fibrosis. PMID- 8219138 TI - Thoracic lesions: diagnosis by ultrasound-guided biopsy. AB - We reviewed the results of US-guided fine-needle biopsies of peripheral pulmonary, pleural, mediastinal and chest wall lesions in 200 patients. Sufficient material for cytological analysis was obtained in 95%, 92%, 96% and 100%, respectively. Sensitivity was 88%, 94%, 96%, 100% and specificity 89%, 100% and 100%, respectively. The ratio of false-negative results was 7%. A cutting needle biopsy was additionally performed in 24 patients. All but two of the histological samples (92%) were adequate for diagnostic purposes and a correct diagnosis was established in 86% (19/22) of these. 8 patients (4%) with pleural or pulmonary targets had minor complications (5 pneumothorax, 3 haemoptysis), which did not require treatment. Cutting needle biopsies and biopsy of mediastinal lesions proved safe. Due to the many advantages US may be considered for guidance in peripheral larger-sized pulmonary lesions, particularly those abutting the pleura, and also in pleural, thoracic wall and mediastinal masses. PMID- 8219139 TI - [The initial results of the implantation of self-expanding nitinol stents into the esophagus in malignant dysphagia]. AB - Nine patients (mean age 64, range 51-83 years), with dysphagia due to incurable malignant obstruction of the esophagus were treated by the introduction of 10 self-expanding metal endoprostheses (Nitinol stents). All cases were technically and functionally successful. In one patient the stent did not expand completely; it had to be removed and a second introduced. There were no other complications from the stent implantation. During the period of observation of 136 +/- 86 days one stent (11%) was reobstructed by tumor growing into the stent. Two patients died after 60 and 119 days, both with open stents. Early experience with the Nitinol stent indicates that good palliation of malignant dysphagia can be achieved with a much lower complication rate than results from tube implantation. The design and application system of the stent is capable of further improvement. PMID- 8219140 TI - [The laser-assisted balloon angioplasty of insufficient hemodialysis-access fistulae]. AB - Patients with end-stage renal failure frequently develop venous stenoses or occlusions in their haemodialysis access fistulas caused by intimal fibrosis. A complete dilation with high pressure balloons up to 20 atm may be unsuccessful in such cases. We investigated two pulsed dye laser devices for the ablation of obstructions, which were not adequately treatable with a previous balloon angioplasty. From 11/90 to 4/92 a total amount of 154 PTAs of haemodialysis access fistulas were performed. In 23 of them additive laser angioplasty was necessary. 20 patients with Cimino fistulas presented 28 stenoses and two occlusions, whereas all the three patients with Goretex loops presented with occlusions. Two pulsed dye laser devices emitted at the wavelengths 504 nm (green) and 595 nm (red). Technical success was achieved in 22/23 cases, but clinical success was obtained in only 20/23 patients, due to two early reocclusions caused by thrombosis. 5 restenoses occurred two, three, 10, and twice 14 months after angioplasty with a mean follow-up period of 13.5 (5-18) months. Pulsed dye laser ablation in haemodialysis access fistula lesions due to intimal fibrosis greatly enriches radiological recanalisation techniques and is a valuable alternative to surgery if stand-alone balloon PTA fails. PMID- 8219141 TI - [The premedication of PTA. A double-blind and randomized comparison of midazolam/tramadol versus placebo/tramadol]. AB - A prospective, randomised and double blind comparative study of Midazolam/Tramadol or placebo/Tramadol for premedication before PTA was carried out on 40 patients (12 female and 28 male, average age 66.1 +/- 12). The anxiolytic, analgesic and general findings were quantified by means of a visual analogue score. Pre- and peri-interventional blood gas, blood pressure and pulse rates were determined. The complications of the two schemes were compared. 19 patients received Midazolam/Tramadol and 21 placebo/Tramadol. Patient anxiety was reduced significantly from 25.8 +/- 25 to 4.3 +/- 6 by premedication. Significant increase in the pain score during PTA was observed only in the placebo group (4.3 +/- 12.6 to 27.4 +/- 20.9). There was no difference in the incidence of complications and respiratory depression due to the Midazolam/Tramadol combination was not observed. PMID- 8219142 TI - [Conventional local intra-arterial fibrinolysis, spray lysis and mechanically accelerated fibrinolysis. An assessment of their position in the spectrum of angioplasty technics]. AB - Intra-arterial local fibrinolysis was performed in 72 patients (51 men, 21 women, mean age 66.8 years) during the course of 78 angioplasties. 11.1% were stage IIa (Fontaine), 38.9% were stage II b, 27.8% were stage III and 22.2% were stage IV. The methods used were conventional fibrinolysis (15.4%), spray lysis (47.4%) and mechanically accelerated fibrinolysis (37.2%). In 66.7% the urokinase dose was < 600,000 I.U., in 17.9% it was > 1,000,000 I.U. Additional balloon dilatation was performed in 72 cases, percutaneous aspiration of thrombo-embolic material in 41 cases and stent implantation in 7 cases. Angiographically the procedure was successful in 90.7%; the Doppler index rose from 0.47 +/- 0.27 to 0.85 +/- 0.3 (p < 0.001). At discharge, staging was: I = 38.9%, IIa = 38.9%, IIb = 5.6%, III = 1.4%, IV = 15.3%. There were no systemic bleeding complications. In 5.1%, complications had to be treated surgically. PMID- 8219143 TI - [The imaging diagnosis of acute cerebral tuberculosis]. AB - 5 unusual cases of cerebral tuberculosis are reported. Three of the cases initially showed the typical history and aspect of herpes simplex encephalitis, and two of a cerebral tumour. Both CT and MRI, and also the clinical neurological symptoms, were confusing. Microbiological culture in three and histological preparation in two cases confirmed the diagnosis of cerebral tuberculosis. Three cases showed the development of tuberculomas under therapy. The study of the literature suggests that this is not rare, which is explained by pathogenetic reflexions concerning the allergic genesis of the tuberculomas. PMID- 8219144 TI - [The postoperative MR tomographic findings following the removal of a hypophyseal adenoma]. AB - 36 patients with pituitary adenomas were examined via MRI to describe physiological changes and to visualise a residual tumour. Pre- and postoperative examinations included T1- and T2-weighted SE sequences. T1-weighted images were obtained in sagittal and coronal orientation pre- and post-Gd-DTPA application and T2-weighted images in coronal orientation. In 12 cases a residual tumour was found. Its signal intensity and contrast enhancement were similar to those of the primary tumour. Implanted material could be distinguished by localisation, decrease in volume and different signal intensity. The behaviour of contrast enhancement was helpful, since implanted material showed a rim enhancement. In our experience a sensitive imaging protocol in the follow-up of operated pituitary adenomas would be an early examination three months postoperatively followed by a control examination after one year. Information on the size and localisation of the primary tumour and the performed operative procedure is essential. PMID- 8219145 TI - [Computer-assisted speech recognition and display of x-ray findings]. AB - A voice recognition system, called Tangora, has been designed for the German language; its prototype has been tested to assess its clinical usefulness for radiological reporting. Its technical vocabulary consists of 20,000 words. The system recognises words spoken provided short pauses are inserted. The Tangora system was compared with conventional methods of dictation, using 68 radiological reports. The work necessary for each system was analysed. The average time taken by the Tangora system per report was 671 seconds compared with 182 seconds for conventional dictation but improvements in the speed of the new system for radiological reporting is to be expected. PMID- 8219146 TI - [The marking of nonpalpable breast tumors in MRT]. PMID- 8219147 TI - [Cerebral toxocariasis]. PMID- 8219148 TI - [A progressive paraplegic syndrome in cervical arachnoid cysts]. PMID- 8219149 TI - CT and MRI of laryngeal amyloidosis. PMID- 8219150 TI - [Multifocal bronchiolo-alveolar carcinoma]. PMID- 8219152 TI - Current concepts in polishing composite resins. AB - The aesthetic appearance of composite resin is based upon shape, color, and gloss of the restoration, achieved by finishing and polishing. The smaller the composite resin filler and the more resin polymer present in the restorative material, the higher the attainable luster. This article examines the recent changes and improvements in materials and techniques of polishing and finishing the macrofill, hybrid, and microfill restorations. PMID- 8219151 TI - [The direct demonstration of a pleuroperitoneal fistula by peritoneography in a secondary Budd-Chiari syndrome]. PMID- 8219153 TI - Freehand composite veneering-the direct option. AB - Freehand bonding of direct composite resin veneers is one of the new techniques developed during the past decade. This article discusses the clinical procedure of this technique, with indications and contraindications, and a new composite resin material used in this technique. PMID- 8219154 TI - Composite resin systems for posterior restorations. AB - Significant improvements have taken place in the composite resin systems during the last 20 years. The author discusses the principles of photoenergy for curing, the optimization of particle size, the placement of posterior composite resins, and the three techniques for placing composite resin inlays and onlays. PMID- 8219155 TI - Clinical evaluation of a new generation universal bonding system for conservative aesthetic restoration. AB - This study evaluated the clinical effectiveness of a new generation bonding material, used for conservative restoration of cervical erosion lesions. One hundred lesions were selected. At two-year recall, 79 have been reviewed to date. In those, 97.5% of the restorations were still present; 95% of restorations present had retained color, 96% had retained marginal integrity, and 100% had retained abrasion resistance, surface texture, and staining resistance. PMID- 8219156 TI - Class II direct composite resin restorations using the prepolymerized ball technique. AB - The use of composite resin restoration materials and techniques has advanced steadily since the early 1980s, with innovations and improvements in products and application procedures. This article discusses one of the most up-to-date composite resin restoration materials and the technique of placing a prepolymerized resin ball into an appropriately prepared cavity, thereby maintaining contact and contour of the restoration. PMID- 8219157 TI - Porcelain veneers: concept, preparation, temporization, laboratory, and placement. AB - The success of porcelain veneers depends on knowledge of chairside and laboratory techniques. Improvements in porcelain materials and techniques have dramatically increased the ease and success of these procedures. The learning objective of this article is a review of the new porcelain veneer techniques. The same case is followed from conception to completion, describing and illustrating the techniques. PMID- 8219158 TI - Treatment of the adolescent trauma patient with endosseous implants: a case study. AB - Adolescent patients who lose permanent dentition through trauma require treatment that considers factors not involved in the treatment of adults. Endosseous implants and a temporary prosthesis were utilized in this case to provide optimum aesthetics in a manner that addressed the evolving dentition, growing skeletal bases, and social and psychologic needs. The learning objective of this case study is the treatment of adolescent trauma and a detailed surgical procedure. PMID- 8219159 TI - Do we need another specialty? PMID- 8219160 TI - Utilization of composite resins and direct bonding following periodontal treatment. AB - When restoring dentition compromised by periodontal treatment, good aesthetics must be achieved without compromising the periodontal health. Improved composite resin systems and new dentin bonding agents offer excellent restorative options. The learning objective of this article is a review of composite resins and direct bonding for aesthetic restorations. Two cases are presented to illustrate the procedure. PMID- 8219161 TI - Methods for aesthetic evaluation in replacement of ceramic fixed prosthetics. AB - After numerous years in situ, ceramic fixed prostheses appear high in value when compared with the adjacent natural teeth, and the patient may desire the replacement of the prosthesis primarily for aesthetic reasons. This article provides exact information on preoperative shade evaluation, modification of a manufactured shade tab, custom shade fabrication, and soft tissue cast fabrication to help to ensure optimal results. The learning objective of this article is an enhanced understanding of the principles of aesthetic restorations. PMID- 8219162 TI - Management of defects produced by periodontitis. PMID- 8219163 TI - Guided tissue regeneration around dental implants: three case reports. AB - This article demonstrates the use of guided tissue regeneration (GTR) principles for regeneration of bone tissue in jaw bone defects associated with dental implant placement. The learning objective of this article is the technique of bone tissue regeneration using the barrier membranes. Three cases are presented to illustrate the procedure. In all of them, the barrier membrane was used to cover the surgical site after the placement of dental implants and bone grafts. PMID- 8219164 TI - Concept of periodontal plastic surgery. AB - With the development of various reconstructive and regenerative techniques in the 1980s, mucogingival surgery evolved into periodontal plastic surgery. This article highlights the surgical procedures which currently can be classified under the concept of Periodontal Plastic Surgery. The learning objective of this article is a review and update of these surgical procedures. PMID- 8219165 TI - An iconoclastic mood. PMID- 8219166 TI - Pedicle flaps, gingival grafts, and connective tissue grafts in aesthetic treatment of gingival recession. AB - Gingival recession leading to exposure of crown margins or extensive areas of the tooth root can cause significant aesthetic difficulties. Surgical innovations over the last decade have enabled the periodontist to correct such problems with greater predictability and improved aesthetics. The current surgical procedures for treatment of gingival recession are described and illustrated, and criteria for selection of the appropriate procedure are presented. The learning objective of this article is a review of the surgical procedures and an increased predictability in implementation. PMID- 8219167 TI - Osseointegration in the maxilla: a presentation of three treatment plans. PMID- 8219168 TI - Reconstruction of the partially edentulous ridge: gateway to improved prosthetics and superior aesthetics. AB - To restore the partially edentulous ridge to its natural dimensions, reconstruction of the width and height of the deformed ridge is necessary. This article describes the major principles of the reconstruction, presurgical evaluation, pouch procedures, and onlay graft procedures. The learning objective of this article is an enhanced understanding of the reconstruction principles and ability to implement the procedures. Three cases are used to illustrate the procedures. PMID- 8219169 TI - Are you ready for high tech? PMID- 8219170 TI - Aesthetic extractions with calcium sulfate and the principles of guided tissue regeneration. AB - Extraction of maxillary anterior dentition can lead to a deformed ridge which may result in prosthetic difficulties. Compared to secondary soft tissue augmentation procedures, prevention of ridge collapse is a superior approach. A composite graft, consisting of 80% demineralized freeze-dried bone allograft material and 20% calcium sulfate, protected by a barrier composed entirely of calcium sulfate, can prevent ridge collapse. The learning object of this article is an increased understanding of the composite graft principles and the implementation technique. PMID- 8219171 TI - Managing the soft tissue margin: the key to implant aesthetics. AB - Developing a natural contour and anatomically dimensioned soft tissue margin is critical to attaining an aesthetic implant restoration. Anatomically dimensioned temporary healing abutments can be used to guide the soft tissue healing to the size of the tooth to be replaced. This article discusses aesthetics, indications, contour, available sizes of the abutment, crown "ledge," soft tissue maturation, healing time, and predictability of the procedure. The learning objective of this article is an enhanced understanding of the principles and placement technique of the temporary healing abutments. PMID- 8219172 TI - Restoration of a partially edentulous posterior using a new generation PFM restorative. AB - This article presents a recently developed porcelain-fused-to-metal dental material, which combines strength and durability with aesthetics and can be used in the anterior as well as posterior regions. Developed in Europe, this system is now available in the United States and can be used in conjunction with all conventional restorations. In the case presented, this material was used with a gold-casted premachined plastic screw-type attachment, and a case report is used to illustrate the clinical procedure. PMID- 8219173 TI - The human dimension of tuberculosis control. PMID- 8219174 TI - Diagnostic and therapeutic thoracoscopy: techniques and indications in pulmonary medicine. AB - Recently thoracoscopy has been used with increasing frequency for the diagnosis and treatment of pleuropulmonary diseases. METHODS: The main requirements for thoracoscopy are rigid telescopes, forceps, scissors, stapler and a video recorder. The procedure can be performed either under general anaesthesia with or without double lumen intubation or under neuroleptanalgesia after inducing an artificial pneumothorax. At the end of the procedure a chest tube should always be inserted even if it is only for a few minutes until the lung re-expands after diagnostic thoracoscopy. Complications are exceptional and mortality is less than 0.017%. INDICATIONS AND RESULTS: Thoracoscopy is useful for diagnosis of a number of lung diseases. For pleural effusion, the sensitivity of thoracoscopy is 92-97% and its specificity is 99%. This is much better than needle pleural biopsy and/or fluid cytology. In malignant mesothelioma, thoracoscopy allows accurate staging. Similarly in spontaneous pneumothorax, classification based on the endoscopic aspects of the lung according to the classification of Vanderschueren allows a better selection of therapeutic alternatives. For diffuse pulmonary diseases, thoracoscopic lung biopsy has a sensitivity ranging from 60-98% depending on whether the underlying disease is sarcoidosis, idiopathic fibrosis, collagenous diseases or other rare diseases. Interventional thoracoscopy is a rapidly expanding domain. In this review the most widespread techniques are summarized. Thoracoscopic pleurodesis is performed for pleural effusion. It can be achieved by talc poudrage but other methods are available. For spontaneous pneumothorax, pleurodesis must be associated with treatment of the causal lesions. The other therapeutic procedures described here are sympathectomy for palmar hyperhidrosis, pulmonary biopsy using an endo-GIA stapler and pericardial biopsy. PMID- 8219175 TI - DNA fingerprints of Mycobacterium tuberculosis do not change during the development of rifampicin resistance. AB - Drug-resistant tuberculosis has become a major public health problem. Resistance to rifampicin probably arises through mutations in the mycobacterial RNA polymerase. Patients may acquire rifampicin resistant tuberculosis by three mechanisms: (1) infection with a resistant organism, (2) selection of a sub population of resistant organisms that remain contained whilst the more virulent wild type is present, (3) mutations within the population of bacilli causing the original infection. Sequential isolates of Mycobacterium tuberculosis were collected from 2 patients who developed rifampicin resistance whilst on treatment. One patient was immunosuppressed with HIV-infection; in the other patient the original isolate was also resistant to isoniazid. DNA fingerprinting techniques were used to type the isolates. No differences were found between the fingerprints of isolates from before and after the development of resistance. These data suggest that the third of the mechanisms listed above was responsible for the acquisition of rifampicin resistance in these 2 patients. PMID- 8219176 TI - Tuberculosis in Canada: a focal disease requiring distinct control strategies for different risk groups. AB - Cases of new or reactivated tuberculosis (TB) reported in Canadian residents during 1985-1987 (1984-1988 in the province of Quebec) were analyzed by geographic region relative to the geographic distribution of groups known to be at high risk. The crude incidence rate (per 100,000 population) of TB was calculated by census division (or Region socio-sanitaire in Quebec). Rates of TB by census division ranged from 0 to over 200 per 100,000 population; the average rate for Canada was 8.3 per 100,000. Census divisions with very high rates (over 20 per 100,000) were concentrated in the northern regions, with 80% or more of TB cases occurring among aboriginal persons. Census divisions with moderately high TB rates of 10-19 per 100,000 were located either in northerly regions or in major metropolitan areas; reported TB cases in these areas occurred disproportionately in the aboriginal or immigrant populations. Tuberculosis continues to become more geographically focused and limited to aboriginal Canadians, immigrants and the urban poor. Priority must be given to full implementation of effective prevention and control methods in geographic areas with higher incidence rates. Different methods will be required for different areas depending upon the risk groups present. PMID- 8219177 TI - Nationwide community survey of tuberculosis epidemiology in Saudi Arabia. AB - In the first nationwide community-based survey of the epidemiology of tuberculosis in Saudi Arabia, 7721 subjects were screened in the 5 provinces (using an equal proportional allocation formula) for 2 parameters: (1) prevalence of positive Mantoux test in non BCG vaccinated subjects; (2) prevalence of bacillary cases on sputum culture. The prevalence of positive Mantoux reaction in children aged 5-14 years was 6% +/- 1.8; higher in urban areas (10%), and lower in rural areas (2%), thus classifying Saudi Arabia among the middle prevalence countries. These relatively good results (by Third World standards) could reflect the rise of the standard of living and wide availability of free treatment for active cases with a lowered risk of infection in the community. This view is supported by the fact that in our survey, only one subject grew Mycobacterium tuberculosis in the sputum. However, there were foci of high prevalence of Mantoux reaction in the urban communities in the Western province (20% +/- 8.7 urban; 1% +/- 1.9 rural). The problem may be caused by the fact that the province receives every year over a million pilgrims, some of whom are known to settle illegally and escape the usual screening for tuberculosis imposed on foreign labourers. In conclusion, even in the absence of an enforceable national programme for the eradication of tuberculosis, the economic standard and wide availability of free treatment for active cases has resulted in relatively low rates of prevalence of tuberculin sensitivity in children. The foci of high prevalence in the Western Province require special screening arrangements. PMID- 8219178 TI - Intrathoracic paediatric tuberculosis: a report of 202 cases. AB - Until recently paediatric tuberculosis rates were in decline in developed countries, but more recently there has been a significant change in these trends. Tuberculosis in British Columbia (BC) is centralized and all paediatric cases diagnosed between 1979 and 1988 were reviewed. There were 252 notifications during the study period but 50 cases were excluded (31 extrapulmonary cases, 11 with missing records and 8 because of incorrect diagnoses). There were 109 (54%) female patients. The age range was 4 months-15 years (6.4 +/- 4.1 years). 52% were 5 years old or less. 75 (37.1%) were aboriginal Canadians, 61 (30.2%) were Asian, 50 (24.8%) were Caucasian and 16 (8%) were included in miscellaneous or unknown groups. Primary pulmonary disease occurred in 197 (97.5%); the remaining 5 had post-primary disease. A history of close contact was elicited in 158 children (78.2%). All but 8 (4%) had a positive PPD response to 5TU. 40% of children had symptoms, the most frequent being cough (51%) and fever (28.4%). Mycobacteriology was carried out in 169 (83.7%) children. Bacteriologic confirmation was achieved in 45 patients (22.2%). Chest X-rays were reviewed in 186 cases. Lymphadenopathy occurred in 93.5%, with hilar (34%) and combined hilar paratracheal (26%) being the commonest findings. The majority of patients were treated with isoniazid and rifampin, with a minority receiving streptomycin or pyrazinamide in the initial intensive phase. 14 (6.9%) children had adverse reactions to their drugs but these were rapidly reversed with the withdrawal of the responsible drug. Response to therapy was excellent and there were no deaths. PMID- 8219179 TI - The impact of intensified supervisory activities on tuberculosis treatment. AB - A Health Subcentre-based randomized controlled trial was conducted in order to determine the importance of the motivation of the tuberculosis personnel in improving the results of a treatment programme. A total of 1300 newly detected tuberculosis patients from 7 Health Centres were divided into study and control groups using the Health Subcentre areas as sampling units. In the study group, worker motivation was intensified through special regular sessions and closer supervision, while in the control group the usual procedures were followed. Treatment performance was remarkably improved in the study areas: treatment completion rate was 78.8% in the study group, compared with 65.2% in the control group. Bacteriological conversions among those having completed the treatment were 91.9% and 62.2% respectively, and overall efficacy was 75.2% and 45.8%, respectively. In addition to improved treatment, the follow-up case examinations also showed markedly increased performance. Although this study was done in facilities using conventional regimens which have been replaced with short-course regimens more recently, the study results still clearly indicate the importance of motivating personnel in the field to attain better case management. PMID- 8219180 TI - The impact of HIV on resource utilization by patients with tuberculosis in a tertiary referral hospital, Nairobi, Kenya. AB - By using routinely collected data and results from research studies at the Infectious Diseases Hospital (IDH), Nairobi, we have begun to determine the scale of the increase in resource utilisation and treatment costs for tuberculosis control services caused by the HIV epidemic. New cases of tuberculosis registered annually at the IDH rose 61%, from 447 in 1985 to 720 in 1990. HIV seroprevalence among patients with tuberculosis rose from 7.5% in 1986 to 42% in 1990. The inpatient mortality rate rose from 8.4% in 1985 to 16.8% in 1989, but fell to 13.5% in 1990. HIV-positive patients were admitted to hospital on 2 or more occasions more often than HIV-negative patients (Relative risk (RR) = 2.46, 95% confidence intervals (CI), 1.1-5.7), but average duration of admission was similar for the 2 groups. Significantly more HIV-positive patients were prescribed antibiotics, antifungal agents, antidiarrhoeal agents, analgesics and corticosteroids than HIV-negative patients. Microbiological investigations, apart from those for tuberculosis, were performed more commonly among HIV-positive patients (RR = 2.0, 95% CI 1.0-4.2). Using this data, the average cost of ideal drug therapy, including antituberculosis drugs and treatment for intercurrent infections and other complications, was estimated using 1992 prices (ECHO, Coulsdon Surrey, UK). The costs were US$16.62 and US$32.94 for HIV-negative patients using 'standard' therapy (2STH/10TH) and short course therapy (2SHRZ/6TH) respectively, and US$41.18 for HIV-positive patients using a short course regimen without thiacetazone (2EHRZ/6EH). The HIV epidemic is causing both an increase in the numbers of patients requiring treatment and an increase in the average cost of treatment per patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219181 TI - Current problems in treating tuberculosis in Italian HIV-infected patients. AB - 31 Italian HIV-infected patients with newly diagnosed tuberculosis (TB) were reviewed to verify the effectiveness of the most common antituberculosis drugs. The patients were mostly intravenous drug addicts (90%), and 14 (45%) had recently been in prison. 5 patients (16%) had pulmonary TB, 15 (48%) had both pulmonary and extrapulmonary involvement, and 11 (30%) had extrapulmonary disease alone. 6 patients received the association of HRZ, and a 4-drug association including ethambutol was given to an additional 7 patients. The remaining 18 patients were administered the association of HRE. Response to therapy was good in 13 patients (42%), and lacking or delayed in 18 patients (58%). Treatment failure was partly related to the increased occurrence in our area of Mycobacterium tuberculosis strains resistant to the first-line anti-tuberculosis drugs. These observations, along with the need of a faster response to therapy than that currently obtained for TB in AIDS and in view of epidemiological effects, should prompt the definition of alternative therapeutic and prophylactic regimens. PMID- 8219182 TI - Six years' experience with the discontinuation of BCG vaccination. 2. Cost and benefit of mass BCG vaccination. AB - In 1986 the compulsory mass BCG vaccination of infants born in a selected area of the Czech Republic was abolished. The observed annual risk of tuberculous infection in children aged 0-6 years was below 0.1% and the annual risk of tuberculous disease 7/100,000. The increase of tuberculous cases among nonvaccinated children indicated a protective efficacy of BCG vaccine of 80%. A benefit analysis proved that the advantages and disadvantages of BCG vaccination were in balance. The number of nonvaccinated children developing tuberculosis was so small that mass application of BCG has been found to be redundant. The important advantage of not using the vaccination is the maintenance of the epidemiological and diagnostic value of tuberculin tests. The tests in connection with preventive chemotherapy remain an important tool, enabling control of infected individuals. PMID- 8219183 TI - Deletions within the LMP1 oncogene of Epstein-Barr virus are clustered in Hodgkin's disease and identical to those observed in nasopharyngeal carcinoma. AB - This study of 52 European patients with Hodgkin's disease (HD) expressing the latent membrane protein 1 (LMP1) oncogene within diagnostic Hodgkin and Reed Sternberg (HRS) cells was performed to detect LMP1 isolates carrying deletions and to characterize them at a molecular and histologic level. Deletions were identified in 5 cases, clustered near the 3' end of the LMP1 gene, and histologically associated with numerous HRS cells. DNA sequencing showed homology with the deletions seen in the Asian nasopharyngeal carcinoma (NPC) isolates CAO and 1510. Our findings suggest that partial deletions of the LMP1 oncogene, associated with aggressive behavior in NPC CAO and NPC 1510, occur at a particular localization and confer a proliferative phenotype to lymphoid cells in HD. PMID- 8219184 TI - Detection of ALL-1/AF4 fusion transcript by reverse transcription-polymerase chain reaction for diagnosis and monitoring of acute leukemias with the t(4;11) translocation. AB - The chromosomal breakpoints of t(4;11) translocation of acute lymphoblastic leukemia (ALL) have been recently identified at molecular level and shown to involve the AF4 (FEL) gene on chromosome 4 and the ALL-1 (MLL, Hrx) gene on chromosome 11. The ALL-1/AF4 fusion gene is transcribed into a chimeric mRNA. Using primer sets derived from ALL-1 and AF4 cDNAs by reverse transcription polymerase chain reaction (RT-PCR), we were able to amplify the breakpoint sites of the fusion transcript of all 15 ALL cases with karyotypic or molecular evidence of the t(4;11). DNA fragments of different size were obtained as the consequence of different breakpoints on chromosome 11 and the presence of alternative splicing of ALL-1 exon 8. The feasibility of monitoring the residual cells carrying the t(4;11) in 2 ALL patients with different clinical outcome was evaluated. Overall, the presented results provide evidence that RT-PCR can be used as a rapid method for detecting this chromosomal abnormality and following the patient's response to therapy. PMID- 8219185 TI - A gene for a myosin peptide is disrupted by the inv(16)(p13q22) in acute nonlymphocytic leukemia M4Eo. AB - Chromosome 16 aberrations are well known in acute nonlymphocytic leukemia (ANLL). The most frequent chromosome 16 aberration in ANLL subtype M4Eo is the inv(16)(p13q22). Recently, we showed that in 5 inv(16) patients with ANLL M4Eo the short arm breakpoints are clustered within a 14-kb genomic EcoRI fragment. We report here the identification of a gene situated in the 14-kb fragment. The gene, which codes for a myosin peptide, is disrupted by the inversion of chromosome 16 in the 5 patients. To the best of our knowledge, this is the first report of a myosin gene disrupted in leukemia. PMID- 8219186 TI - Combined spectrin and ankyrin deficiency is common in autosomal dominant hereditary spherocytosis. AB - The common autosomal dominant form of hereditary spherocytosis (HS) has been genetically linked to defects of the erythroid ankyrin gene in a few families; however, the frequency of ankyrin deficiency and its relationship to red blood cell (RBC) spectrin content are unknown. To test these questions, we measured RBC spectrin and ankyrin by radioimmunoassay in 39 patients from 20 families with dominant HS. Normal RBCs contained 242,000 +/- 20,500 spectrin heterodimers and 124,500 +/- 11,000 ankyrins per cell. In dominant HS, RBC spectrin and ankyrin ranged from about 40% to 100% of normal and were continuously distributed. Measurements in the same patient on different occasions were reproducible (+/- 5% to 10%) and RBCs from affected members of a kindred contained similar amounts of spectrin and ankyrin (+/- 3% to 4%). Spectrin and ankyrin levels were almost always less than the assay controls, but were less than the normal range in only 75% and 80% of kindreds, respectively. Remarkably, the degree of RBC spectrin and ankyrin deficiency was very similar in 19 of 20 HS kindreds. One otherwise typical family differed, with marked ankyrin deficiency (45% of control) and a relatively mild spectrin deficit (81%). We conclude that most patients with dominant HS have combined ankyrin and spectrin deficiency and that the two proteins are usually about equally deficient, suggesting that defects in ankyrin expression, ankyrin stability, or ankyrin band 3 (AE1) interactions may be common in dominant HS. PMID- 8219187 TI - Splenectomy and/or bone marrow transplantation in the management of the Wiskott Aldrich syndrome: long-term follow-up of 62 cases. AB - This study describes the effects of two major treatment options, splenectomy and/or bone marrow transplantation, on the natural history of the Wiskott-Aldrich (WAS) syndrome. The records of 62 patients with the WAS evaluated at the National Institutes of Health Clinical Center from 1966 to 1992 were reviewed. Nineteen patients were treated with bone marrow transplantation (BMT) and the results were largely dependent on the source of the graft. Twelve of 12 patients receiving HLA matched sibling marrow achieved satisfactory immunologic and hematologic reconstitution. By contrast, only 2 of 7 patients receiving haploidentical, parental, or matched unrelated marrow survived more than 1 year after BMT. Thirty nine patients who lacked suitable bone marrow donors early in their course underwent splenectomy for management of their thrombocytopenia; most received prophylactic antibiotics to minimize the risk of sepsis. Nearly all these patients achieved normal platelet counts and the rate of serious bleeding was reduced nearly sevenfold. Median survival in the untransplanted splenectomy group was 25 years, compared with less than 5 years in unsplenectomized patients. We conclude that HLA-matched sibling donor BMT is the treatment of choice for patients with WAS and that splenectomy and daily prophylactic antibiotics provide a significant survival advantage to those boys without a matched sibling donor. Splenectomy should probably be used in preference to unmatched BMT until results with alternative donor BMT significantly improve or gene therapy becomes available. PMID- 8219188 TI - All-trans retinoic acid in patients with myelodysplastic syndromes: results of a pilot study. AB - Considering the beneficial effect of all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL), it has been speculated that ATRA might also be useful for treating other hematologic malignancies. To test this hypothesis, we performed a dose-escalating 3-month-trial of ATRA in 15 patients with primary or secondary myelodysplastic syndromes (MDS). Morphologic diagnoses were refractory anemia (RA) in 4, RA with ring sideroblasts (RARS) in 2, RA with excess blasts (RAEB) in 7, and RAEB in transformation (RAEB/T) in 2 cases. Patients included were required to have one or more of the following criteria: transfusion dependent anemia, pronounced neutropenia (< or = 0.5 x 10(9)/L) or thrombocytopenia (< or = 20 x 10(9)/L), or increasing blast cells in the peripheral blood or bone marrow. Therapy was started at an ATRA dose of 30 mg/m2/d, administered orally as two doses of 15 mg/m2 every 12 hours. The retinoid dose was increased to 60 mg/m2/d after 4 weeks and to 90 mg/m2/d after 8 weeks. Among 14 patients assessable for response, none obtained a complete or partial remission. Three patients had a minor response, manifested by either reduction in transfusion requirements (2 patients) or increase in neutrophil and platelet counts (1 patient). During the study period, 5 patients progressed to more advanced stages of MDS or overt leukemia. Three patients with chromosomal abnormalities receiving ATRA for a period of 10 to 12 weeks retained their cytogenetic marker after completion of treatment. Side effects of ATRA primarily affected the skin and mucous membranes, with 13 of 15 patients having at least low-grade dermatologic toxicity. In 2 cases, treatment had to be prematurely stopped because of intolerable conjunctivitis or progressive neurologic symptoms. These data suggest that ATRA has little effect on MDS. The lack of response of MDS patients, as compared with those with APL, may be attributed to the absence of the t(15;17) translocation that seems to be a prerequisite for clinical efficacy of ATRA. PMID- 8219189 TI - Prolonged subcutaneous administration of recombinant alpha 2b interferon in patients with previously untreated Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia: effect on remission duration and survival: Cancer and Leukemia Group B study 8583. AB - We investigated whether recombinant alpha 2b interferon (r alpha 2bIFN) would reduce the proportion of bone marrow Philadelphia chromosome (Ph) cells in chronic-phase chronic myelogenous leukemia (CML) by treating 107 previously untreated patients daily with r alpha 2bIFN at 5 x 10(6)IU/m2 subcutaneously. Patients with complete remission, partial remission, or partial hematologic remission received treatment until progression; those with progressive disease were taken off study and observed for survival. Sixty-three (59%) of the patients achieved at least a partial hematologic remission (24 complete remissions and 39 partial remissions). The median time to response for the 63 responders was 3.4 months, with a median duration of remission of 52 months and with 81% of responders continuing in remission beyond 12 months. The median survival for the 107 patients was 66 months. Of 78 patients with cytogenetic follow-up data, 31 (40%) achieved a partial cytogenetic response (n = 17) or a complete cytogenetic response (n = 14). The percentage of cytogenetic responders among all patients was 29% (31 of 107 patients). The median time to first cytogenetic response was 9 months. A major dose reduction of r alpha 2bIFN (> or = 50%) was required at some time during treatment in 38% of patients, 26% required 10% to 49% dose reductions, and 36% had minor dose reductions of < or = 10%. No association was observed between dose received and the attainment of a cytogenetic response. None of the usual prognostic factors (sex, race, performance status, weight loss, time from diagnosis to treatment, hepatosplenomegaly, age, symptoms, hemoglobin, or platelet, blast, basophil, or white blood cell count) were significantly related to survival. These data provide confirmation that major cytogenetic responses to prolonged administration of subcutaneous r alpha 2bIFN occur in 20% to 38% (95% confidence interval) of chronic-phase Ph-positive patients. Although it is hypothesized that patients achieving major cytogenetic responses to r alpha 2bIFN should have prolonged remission duration and survival compared with nonresponders, analyses of the effect of cytogenetic responders by both "landmark" and time-dependent covariate techniques fail to provide statistically significant evidence for an effect of cytogenetic response on remission duration or survival. This may be due in part to an effect size insufficiently large to be detected with the number of patients treated in this study. Thus, confirmation of remission duration or survival benefit, if any, of r alpha 2bIFN therapy in Ph positive chronic-phase CML must await the outcome of randomized trials comparing IFN with conventional agents. PMID- 8219190 TI - Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans. AB - Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin-induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra. PMID- 8219191 TI - Hematopoietic lineage- and stage-restricted expression of the ETS oncogene family member PU.1. AB - The ETS oncogene family member PU.1 is a transcriptional activator that is dysregulated by Friend erythroleukemia virus insertion. Northern analysis found that PU.1 is highly expressed in cells of myeloid and B-lymphoid origin, but not expressed at all in a number of nonhematopoietic tissues. Interferon-gamma and retinoic acid downregulated PU.1 expression in marrow macrophages. In situ immunohistochemistry found that PU.1 is expressed only in early granulocytic and erythroid cells and megakaryocytes, but not in mature erythroid cells, mature granulocytes, endothelial cells, or osteocytes. Thus, its expression pattern makes PU.1 a candidate for a genetic determinant of lineage commitment and stage progression in blood cell development. It also lends insight into how PU.1 might play a role in Friend virus erythroleukemia. PMID- 8219192 TI - Combination protocols of cytokine therapy with interleukin-3 and granulocyte macrophage colony-stimulating factor in a primate model of radiation-induced marrow aplasia. AB - Single cytokine therapy with granulocyte-macrophage colony-stimulating factor (GM CSF) or interleukin-3 (IL-3) has been shown to be effective in decreasing the respective periods of neutropenia and thrombocytopenia following radiation- or drug-induced marrow aplasia. The combined administration of IL-3 and GM-CSF in normal primates suggested that a sequential protocol of IL-3 followed by GM-CSF would be more effective than that of GM-CSF alone in producing neutrophils (PMN). We investigated the therapeutic efficacy of two combination protocols, the sequential and coadministration of recombinant human IL-3 and GM-CSF relative to respective single cytokine therapy, and delayed GM-CSF administration in sublethally irradiated rhesus monkeys. Monkeys irradiated with 450 cGy (mixed fission neutron:gamma radiation) received either IL-3, GM-CSF, human serum albumin (HSA), or IL-3 coadministered with GM-CSF for days 1 through 21 consecutively postexposure, or IL-3 or HSA for days 1 through 7 followed by GM CSF for days 7 through 21. All cytokines and HSA were injected subcutaneously at a total dose of 25 micrograms/kg/d, divided twice daily. Complete blood counts (CBC) and platelet (PLT) counts were monitored over 60 days postirradiation. The respiratory burst activity of the PMN was assessed flow cytometrically, by measuring hydrogen peroxide (H2O2) production. Coadministration of IL-3 and GM CSF reduced the average 16-day period of neutropenia and antibiotic support in the control animals to 6 days (P = .006). Similarly, the average 10-day period of severe thrombocytopenia, which necessitated PLT transfusion in the control animals, was reduced to 3 days when IL-3 and GM-CSF were coadministered (P = .004). The sequential administration of IL-3 followed by GM-CSF had no greater effect on PMN production than GM-CSF alone and was less effective than IL-3 alone in reducing thrombocytopenia. PMN function was enhanced in all cytokine-treated animals. PMID- 8219193 TI - Mechanisms of tumor necrosis factor-granulocyte-macrophage colony-stimulating factor-induced dendritic cell development. AB - In a previous report, we described that tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) synergistically enhanced the development of dendritic cell (DC) progeny from early stem cells and that there is a common monocyte-DC progenitor cell. Low levels of DC were obtained with GM-CSF alone, and TNF by itself failed to induce stem cell development. Here, we investigate mechanisms by which TNF and GM-CSF institute increases in DC, and how these same molecules support later stages of DC differentiation. We show that TNF is required as the first signal, that there is upregulation of GM-CSF receptors (GM-CSFRs), and that TNF inhibits the differentiation of colony-forming units-granulocyte. High levels of GM-CSFR were always associated with conditions yielding a large number of DC, and a kinetic analysis showed a close ontogenic relationship between DC and GM-CSFR levels. The addition of anti-GM-CSF or anti-TNF antibodies blocked synergistic responses related to DC development, including high levels of GM-CSFRs. Anti-GM-CSF was the most potent inhibitor of proliferation (80%) and macrophage, DC, and polymorphonuclear (PMN) cell development. With polyclonal anti-TNF, inhibition was less (35%), and there was a shift from myelomonocytic and DC to PMN progeny. Our results support the concept that receptor upregulation is an important mechanism for growth factor synergy. Our data also indicate that the opposing effects of TNF on hematopoiesis contribute to the selection of the DC pathway and emphasize the importance of GM-CSFRs not only in initiated DC development, but also in controlling DC viability and function. PMID- 8219194 TI - Platelet adhesion to cyanogen-bromide fragments of collagen alpha 1(I) under flow conditions. AB - The aim of this investigation was to identify domains of collagen type I that can support platelet adhesion under flow conditions. Four cyanogen bromide (CB) fragments composing 87% of the collagen alpha 1(I)-chain were studied under static and flow conditions. Under static conditions, bovine and human collagen fragment alpha 1(I)CB3 induced aggregate formation, whereas alpha 1(I)CB7 and alpha 1(I)CB8 supported adhesion of dendritic and contact platelets. Bovine alpha 1(I)CB6 weakly supported platelet adhesion. At shear rate 300/s, collagen fragment alpha 1(I)CB3 strongly supported platelet adhesion, whereas lower platelet adhesion was observed to alpha 1(I)CB7 and alpha 1(I)CB8. The fragment alpha 1(I)CB6 did not support platelet adhesion under flow conditions. Adhesion to alpha 1(I)CB3 was completely inhibited by a low concentration (0.6 IgG microgram/mL) of anti-GPIa monoclonal antibody (MoAb), whereas this concentration of antibody partially inhibited adhesion to alpha 1(I)CB7 and alpha 1(I)CB8. At higher concentrations (3 micrograms/mL) the anti-glycoprotein Ia (GPIa) antibody completely inhibited adhesion to alpha 1(I)CB8 and further reduced adhesion to alpha 1(I)CB7. Platelet adhesion to alpha 1(I)CB3, alpha 1(I)CB7, and alpha 1(I)CB8 was strongly inhibited by an anti-GPIb MoAb. A MoAb against the GPIb binding site of von Willebrand factor (vWF) strongly inhibited platelet adhesion to alpha 1(I)CB7 and alpha 1(I)CB8, whereas platelet adhesion to alpha 1(I)CB3 was not inhibited. We conclude that under flow conditions alpha 1(I)CB3, alpha 1(I)CB7, and alpha 1(I)CB8 support GPIa/IIa-dependent platelet adhesion. The GPIb vWF interaction is important under flow conditions for adhesion to alpha 1(I)CB7 and alpha 1(I)CB8 and probably also to alpha 1(I)CB3. PMID- 8219195 TI - Activation of human platelets by immune complexes prepared with cationized human IgG. AB - The present study shows that the ability of soluble immune complexes (IC), prepared with human IgG and rabbit IgG antibodies against human IgG, to trigger platelet activation was markedly higher for IC prepared with cationized human IgG (catIC) compared with those prepared with untreated human IgG (cIC). CatIC induced platelet aggregation and adenosine triphosphate release in washed platelets (WP), gel-filtered platelets (GFP), or platelet-rich plasma (PRP) at physiologic concentrations of platelets (3 x 10(8)/mL) and at low concentrations of catIC (1 to 30 micrograms/mL). On the contrary, under similar experimental conditions, cIC did not induce aggregation in PRP, WP, or GFP. Low aggregation responses were only observed using high concentrations of both WP (9 x 10(8)/mL) and cIC (500 micrograms/mL). Interestingly, catIC were also able to induce platelet activation under nonaggregating conditions, as evidenced by P-selectin expression. Cationized human IgG alone did not induce platelet aggregation in PRP but triggered either WP or GFP aggregation. However, the concentration needed to induce these responses, was about eightfold higher than those required for catIC. The responses induced either by catIC or cationized human IgG were completely inhibited by treatment with heparin, dextran sulphate, EDTA, prostaglandin E1, or IV3, a monoclonal antibody against the receptor II for the Fc portion of IgG (Fc gamma RII). The data presented in this study suggest that IgG charge constitutes a critical property that conditions the ability of IC to trigger platelet activation. PMID- 8219196 TI - Cloning of the complete Ly-6E.1 gene and identification of DNase I hypersensitive sites corresponding to expression in hematopoietic cells. AB - The Sca-1 antibody recognizes antigens encoded by members of the Ly-6 multigene family. These antigens are expressed on fetal and adult hematopoietic stem cells, progenitor cells, mature activated T cells, and some nonhematopoietic cells and are most likely encoded by the Ly-6E.1 and Ly-6A.2 genes. Characterization and isolation of regulatory elements of Ly-6E.1 and A.2 genes that govern tissue specific and high levels of expression in the cells of the hematopoietic system (particularly stem cells) are of considerable interest. To characterize the control elements of this gene, we have cloned a 30-kb fragment encoding a fully functional Ly-6E.1 gene and 13 kb of 5' and 13 kb of 3' flanking sequence. Transfection studies in murine erythroleukemia (MEL) cells show that a 14-kb BamHI fragment from this clone is sufficient to confer Ly-6E.1 gene expression at levels equivalent to those of the endogenous gene. By mapping regions of chromatin sensitive to DNase I digestion, we have located hypersensitive sites in the 5' and 3' regions of the gene in FDCP-1 cells, MEL cells, and various T-cell lines. The appearance of two 5' hypersensitive sites in hematopoietic cells correlates with Ly-6E.1 expression after gamma-interferon induction. We show that the presence of hypersensitive sites in the 5' and 3' regions corresponds to Sca 1 expression, and we also discuss the localization of putative regulatory control elements. PMID- 8219197 TI - Southern blot patterns, frequencies, and junctional diversity of T-cell receptor delta gene rearrangements in acute lymphoblastic leukemia. AB - Southern blot analysis of T-cell receptor (TCR)-delta gene rearrangements is useful for diagnostic studies on the clonality of lymphoproliferative diseases. We have developed 18 new TCR-delta gene probes by use of the polymerase chain reaction (PCR) techniques. Application of these probes for detailed analysis of the TCR-delta genes in normal control samples, 138 T-cell acute lymphoblastic leukemias (T-ALL), and 91 precursor B-ALL allowed us to determine the TCR-delta gene restriction map for five restriction enzymes, as well as the Southern blot restriction enzyme patterns of all theoretically possible TCR-delta gene rearrangements. Based on this information, it appeared that 97% of all 213 detected TCR-delta gene rearrangements in our series of ALL could be detected by use of the TCRDJ1 probe and that the majority (76%) of the 213 rearrangements could be identified precisely. In T-ALL, we found a strong preference for the complete rearrangements V delta 1-J delta 1 (33%), V delta 2-J delta 1 (10%), and V delta 3-J delta 1 (7%) and the incomplete rearrangement D delta 2-J delta 1 (11%). In precursor B-ALL, the majority of rearrangements consisted of V delta 2 D delta 3 (72%) and D delta 2-D delta 3 (10%). The junctional diversity of these 6 preferential TCR-delta rearrangements was analyzed and showed an extensive junctional insertion (approximately 30 nucleotides) for complete V delta-J delta rearrangements, whereas incomplete rearrangements had correspondingly smaller junctional regions. The detailed TCR-delta gene restriction map and probes presented here, in combination with the Southern blot patterns of TCR-delta gene rearrangements, are important for TCR-delta gene studies in ALL; all TCR-delta gene rearrangements can be detected and the majority can be identified precisely. Identification of rearrangements is a prerequisite for subsequent PCR analysis of TCR-delta gene junctional regions, eg, for detection of minimal residual disease during follow-up of ALL patients. PMID- 8219199 TI - Soluble CD16 binds peripheral blood mononuclear cells and inhibits pokeweed mitogen-induced responses. AB - Human neutrophils express two types of low affinity receptors for IgG, Fc gamma RII or CD32 and Fc gamma RIIIB or CD16. Human serum contains soluble CD16 (sCD16), which is produced by proteolysis of neutrophil Fc gamma RIIIB, the cleavage site being located close to the cell surface. In order to assess the functional roles of sCD16, we have produced, in eukaryotic cells, a recombinant sCD16 containing the extracellular region of Fc gamma RIIIB. Purified sCD16, of molecular mass of 48 kD, bound human IgG1 and IgG3 but not IgG2, IgG4, or F(ab')2. It inhibited, in a time and dose-dependent fashion, proliferation and IgM and IgG production of human peripheral blood mononuclear cells (PBMC) stimulated by pokeweed mitogen (PWM) in vitro. FACS analysis showed that biotinylated sCD16 bound specifically to a fraction (35%) of PBMC, which corresponds to monocytes and to subsets of B and T lymphocytes. Moreover, sCD16 did not modify the staining of PBMC by FITC-coupled PWM. Thus, the biologic function(s) of sCD16 on PWM-induced responses are exerted through direct and specific interaction(s) with mononuclear blood cells and not with PWM. In conclusion, neutrophils may play a regulatory role on immune responses via the production of soluble forms of CD16 with cell-binding and antiproliferative capacities. PMID- 8219198 TI - Severe thrombocytopenia in an acquired immunodeficiency syndrome patient associated with pentamidine-dependent antibodies specific for glycoprotein IIb/IIIa. AB - Severe thrombocytopenia developed in a patient with acquired immunodeficiency syndrome during treatment with intravenous pentamidine for Pneumocystis carinii pneumonia. The patient's bone marrow contained adequate numbers of megakaryocytes, suggesting peripheral platelet destruction. Platelet counts ranged between less than 3 and 20 x 10(9)/L for 2 weeks despite cessation of pentamidine, platelet transfusions, high-dose intravenous IgG, and 2 mg/kg/d prednisone. Thereafter, the platelet count increased to prepentamidine levels (95 x 10(9)/L0, permitting rapid withdrawal of steroids. Testing by immunofluorescence disclosed a high-titer, pentamidine-dependent IgG antibody in the patient's acute-phase serum that almost entirely disappeared by the time the patient's platelet count returned to baseline levels. This antibody reacted only with platelet glycoprotein (GP) IIb/IIIa as shown by antigen-capture enzyme linked immunosorbent assay using monoclonal antibodies specific for various GPs, and was absorbable by normal, but not by GPIIb/IIIa-deficient platelets (from a patient with Glanzmann's thrombasthenia). The pentamidine-dependent antibody could not be demonstrated by immunoprecipitation using the patient's serum and 125I-labeled normal platelets, although a separate pentamidine-independent antibody was detected by this method. This latter antibody reacted with two GPs having molecular weights consistent with GPIIb/IIIa, and was present in postrecovery as well as acute-phase sera. However, only the pentamidine-dependent antibody was temporally associated with the severe thrombocytopenia. Therefore, we believe that these studies demonstrate, for the first time, that intravenous pentamidine therapy can provoke formation of drug-dependent antibodies that induce immunologic thrombocytopenia. PMID- 8219200 TI - Prevention and induction of occlusive coronary vascular disease in autoimmune (W/B)F1 mice by haploidentical bone marrow transplantation: possible role for anticardiolipin autoantibodies. AB - Male (NZW x BXSB)F1 (W/BF1) mice develop systemic autoimmunity involving autoantibodies, thrombocytopenia, lupus nephritis, and coronary vascular disease with myocardial infarction (CVD). To determine whether this murine lupus associated CVD could be transferred to otherwise autoimmune-resistant (C57BL/6 x C3H/He)F1 (B6C3F1) mice via W/BF1 T-cell-depleted marrow (TCDM) transplants, or conversely whether the CVD of W/BF1 mice could be prevented by the reciprocal transplant, reciprocal haploidentical transplants of TCDM were performed. CVD developed only in mice with systemic autoimmunity. Mice that developed lupus had glomerulonephritis and thrombocytopenia and also had elevated titres of autoantibodies to double-strand DNA, cardiolipin, and platelets and elevated levels of circulating immune complexes. Of control W/BF1 mice, 80% developed lupus, and of these, 81% developed CVD with a mean grade of 2.5 +/- 0.8. Engraftment of W/BF1 mice with B6C3F1 marrow protected 90% of the recipients from the development of lupus, and none developed CVD. Engraftment of B6C3F1 mice with W/BF1 marrow induced lupus in 60% of the recipients, and of those, 33% developed CVD with a mean grade of 1.3 +/- 0.3. The B6C3F1 recipients of W/BF1 marrow which developed CVD had significantly higher titres of autoantibodies to cardiolipin (aCL; P < .01). These findings show that genetic abnormalities present in the W/BF1 hematopoietic stem cells contribute to autoantibody development, including aCL, and suggest that thrombogenic mechanisms induced by aCL may contribute to the development of CVD in this form of murine lupus erythematosus. PMID- 8219201 TI - Trisomy 21 in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study (8602). AB - Of 1,036 children with newly diagnosed non-T, non-B acute lymphoblastic leukemia (ALL) and a demonstrated cytogenetic abnormality treated on the frontline Pediatric Oncology Group (POG) therapeutic trial 8602, there were 33 patients with trisomy 21 as the sole abnormality. Of these 33, 14 had Down syndrome (DS). Although the non-DS (NDS) trisomy 21 cases tended to be older than the DS cases, there were no other significant differences in clinicobiologic features nor in treatment outcomes between the DS and NDS groups, nor between the entire trisomy 21 group and the other chromosome abnormality group. Among NDS patients with +21 and one additional abnormality, +X, +16, -20, and structural abnormalities involving 6q or 12p were common findings. Kaplan-Meier event-free survival (EFS) curves showed a 4-year EFS of 80% (SE, 12%) in NDS trisomy 21 cases, 71% (SE, 22%) in DS cases with trisomy 21 as the sole abnormality, and 69% (SE, 2%) in cases with other chromosome abnormalities. Trisomy 21 as a sole acquired abnormality in NDS patients suggests a good prognosis. PMID- 8219202 TI - High-dose mitoxantrone induces programmed cell death or apoptosis in human myeloid leukemia cells. AB - Mitoxantrone has been shown in vitro to exhibit a steep dose-response relationship with respect to the clonogenic survival of acute myeloid leukemia cells. In this report, we show that 1-hour exposure of human myeloid leukemia HL 60 and KG-1 cells to mitoxantrone concentrations ranging between 0.1 and 10.0 mumol/L induced internucleosomal DNA fragmentation of approximately 200-bp integer multiples, characteristic of cells undergoing programmed cell death (PCD) or apoptosis. Mitoxantrone-mediated PCD was associated with a steep inhibition of the clonogenic survival of the leukemic cells. In addition, intracellularly, mitoxantrone-induced PCD was associated with a marked induction of c-jun and significant repression of c-myc and BCL-2 oncogenes. Pretreatment with the protein kinase C stimulator phorbol myristate acetate enhanced mitoxantrone induced internucleosomal DNA fragmentation, whereas protein kinase C inhibitors staurosporine and H7 had no effect. These findings suggest that PCD is a potential mechanism underlying the steep dose-response relationship of mitoxantrone to the inhibition of clonogenic survival of acute myeloid leukemia cells. PMID- 8219203 TI - Incidence of Waldenstrom's macroglobulinemia. AB - This study sought to determine the incidence and pattern of occurrence of Waldenstrom's macroglobulinemia, a plasmacytoid lymphocyte malignancy that involves monoclonal production of the IgM M-component type. Cases with Waldenstrom's macroglobulinemia have been reported since 1978 to the population based cancer registry that serves western Washington state, and since 1988 to the eight other cancer registries that participate in the National Cancer Institute's Surveillance, Epidemiology, and End-Results program. Persons less than 85 years old newly diagnosed with Waldenstrom's macroglobulinemia were identified through 1989. The age-standardized annual incidence rate was 6.1 per million in white men and 2.5 per million in white women (1980 US standard). Only five cases were reported in black women, among whom the age-standardized annual incidence rate was 3.6 per million. No cases were reported among black men (5.8 cases expected, based on the rates in white men); this finding may be due to chance, underdiagnosis of Waldenstrom's macroglobulinemia in this group, or may reflect a truly low rate. Further investigation of a large, racially diverse population is required to better characterize the epidemiology of this rare disease. PMID- 8219204 TI - The expression of p53 protein in non-Hodgkin's lymphomas is not always dependent on p53 gene mutations. AB - p53 overexpression has been found to be a fairly common feature in high grade lymphomas in the majority of tumoral cells. The results vary from series to series, from 25% to 33% of cases. To assess whether immunohistochemical positivity for p53 correlated with the presence of structural gene abnormalities, DNA from 16 non-Hodgkin's lymphomas with high and low p53 values was amplified and sequenced to determine the existence of point mutations in the highly conserved regions of the p53 gene. In the group of 8 cases containing high levels of protein, 3 cases showed missense point mutations at the codons mapping between exons 5 through 8. Of the 8 cases of tumors containing undetectable or low levels of p53 protein, 1 case presented a nonsense point mutation giving a stop codon. No missense mutations were detected in this group. The finding of p53 mutations in 4 of 16 cases confirms the presence of p53 gene mutations in high grade lymphomas distributed over different histologic groups. These include Burkitt's lymphoma, together with centroblastic, immunoblastic, and large cell lymphoma of mucosa origin. Nevertheless, the absence of mutations in 5 of the 8 cases that overexpressed p53 suggests that the nuclear or cytoplasmic stabilization of p53 protein could also depend on other factors. The absence of detectable levels of p53 protein cannot discount the existence of p53 mutations, as is shown by a case of Burkitt's lymphoma in which a nonsense mutation was detected. The impact of this range of p53 alterations on clinical course and treatment response of the patients deserves to be explored, in an attempt to differentiate the specific consequences of each one. PMID- 8219205 TI - Analysis of p53 mutations in a large series of lymphoid hematologic malignancies of childhood. AB - p53 mutations are found in a wide variety of cancers, including hematologic malignancies. These alterations apparently contribute to development of the malignant phenotype. We analyzed a large series of lymphoid (330 cases) and a smaller series of myeloid (29 cases) malignancies of childhood for p53 mutations by single-strand conformational polymorphism (SSCP) following polymerase chain reaction. Samples with abnormal SSCP were reamplified and analyzed by direct sequencing method. p53 mutations were detected within the known mutational hotspots (exons 5 to 8) in 8 of 330 lymphoid malignancies, and in none of 29 myeloid malignancies, showing that the frequency of p53 mutations in childhood lymphoid malignancies was very low (8 of 330 cases [2%]). Four of these patients had very aggressive, fatal acute lymphocytic leukemia (ALL). None of 13 infants and none of 48 patients with T-lineage leukemia had detectable p53 mutations in their ALL cells. Exceptionally, p53 mutations were comparatively frequent in a small sample of B-cell non-Hodgkin's lymphomas (2 of 8 cases). Mutations were detected in samples from two patients with ALL at relapse; these were not detected in samples at initial diagnosis from the same patients, suggesting that p53 mutations may be associated with progression to a more malignant phenotype. Seven of eight alterations of p53 were missense mutations, and seven of eight samples may be heterozygous for the mutant p53, indicating that p53 protein may act in a dominant negative fashion. PMID- 8219206 TI - Structural and functional heterogeneity among peroxidase-negative granules in human neutrophils: identification of a distinct gelatinase-containing granule subset by combined immunocytochemistry and subcellular fractionation. AB - The existence of separate gelatinase granules in human neutrophils has been a matter of debate in recent years. We have demonstrated that the 135-kD form of neutrophil gelatinase is a complex of 92-kD gelatinase and a novel 25-kD protein termed neutrophil gelatinase-associated lipocalin (NGAL) that, in addition to being complexed with part of the gelatinase, is localized in free form in peroxidase-negative specific granules. Because this association was not appreciated in earlier studies, we decided to reassess the ultrastructural localization of gelatinase using specific antibodies without immunoreactivity towards NGAL. Double-labeling immunogold electron microscopy was performed on frozen thin sections of human neutrophils. Twenty-four percent of all peroxidase negative granules were labeled with antigelatinase antibody, but not with antilactoferrin antibody. These granules are defined as gelatinase granules. Sixteen percent reacted with antilactoferrin antibody but not with antigelatinase antibody. The rest (60%) reacted with both antibodies. All granules labeling for lactoferrin are defined as specific granules. Gelatinase granules were observed as round and oval forms of considerably smaller size than specific granules, and were less electron dense. Isolated granules obtained by subcellular fractionation were also examined by immunoelectron microscopy. This demonstrated that peroxidase-negative granules comprise a continuum from the most dense granules that contain lactoferrin but no gelatinase to the lightest that contain gelatinase but no lactoferrin. Thus, gelatinase granules do exist as a subpopulation of peroxidase-negative granules and may allow for exocytosis of gelatinase during neutrophil diapedesis without substantial mobilization of other peroxidase-negative granules, ie, specific granules. PMID- 8219208 TI - A point mutation in the GYPC gene results in the expression of the blood group Ana antigen on glycophorin D but not on glycophorin C: further evidence that glycophorin D is a product of the GYPC gene. AB - Glycophorin C (GPC) and glycophorin D (GPD) are homologous sialoglycoproteins in the human red blood cell membrane. Both are thought to be encoded by the GPC gene (GYPC). We report that the rare blood group antigen, Ana, is expressed on GPD but not on GPC. cDNA was synthesized from total RNA obtained from two unrelated, heterozygous Ana+ blood donors and analyzed by the polymerase chain reaction using primers that spanned sequences encoded by the GYPC gene. The expected 412 bp fragment was generated, and sequencing of the amplified product showed a G-->T substitution at nucleotide 67 of the coding sequence, resulting in the substitution of alanine by serine at amino acid residue 23 of GPC and, presumably, residue 2 of GPD. To explain the expression of Ana on GPD but not on GPC, we postulate that the conformation of the amino acid residues at the N terminal region of GPD determines the antigenic expression as this conformation would be different from that of the same sequence of amino acids occurring within GPC. Other possible reasons for antigen expression on a shorter protein product but not on the full-length protein product of the same gene are discussed. We extrapolate this reasoning to account for the expression of the common GE2 blood group antigen on GPD but not on GPC. PMID- 8219207 TI - Cloning and expression of the cDNA encoding mouse neutrophil gelatinase: demonstration of coordinate secondary granule protein gene expression during terminal neutrophil maturation. AB - The 92-kD form of human type IV collagenase (gelatinase) is a member of the matrix metalloproteinase family. It is restricted in its expression to the granulocytic lineage of white blood cells. Within neutrophils it resides in secondary granules, which are markers of terminal myeloid differentiation. We have isolated and sequenced the cDNA encoding the murine counterpart to the human 92-kD metalloproteinase from a macrophage cDNA library. The human and murine genes are highly homologous and exist in an identical form in neutrophils and monocyte-macrophages in both species. Two polyadenylation signals are present in the murine 3' untranslated sequence, accounting for equal expression of two messenger RNAs. We have shown that expression of gelatinase mRNA is controlled in a coordinate fashion together with lactoferrin, also a component of neutrophil secondary granules, and that this control occurs at the level of transcription. This is the first definitive demonstration of coordinate transcriptional regulation of secondary granule protein gene expression, a feature of normal myelopoiesis that is deranged in leukemogenesis. PMID- 8219209 TI - Nonrandom association of free iron with membranes of sickle and beta-thalassemic erythrocytes. AB - To further define the nature of abnormal iron deposits on the membranes of pathologic red blood cells, we have used sickle cell anemia (HbSS), HbSC, and beta-thalassemic erythrocytes (RBCs) to prepare inside-out membranes (IOM) and insoluble membrane aggregates (AGGs) containing coclustered hemichrome and band 3. Study of IOM from HbSC and thalassemic patients showed that amounts of heme iron and, especially, free iron were much higher in patients who had undergone surgical splenectomy. The membrane AGGs from HbSS and beta-thalassemic RBCs contained much more globin than heme, with this discrepancy being variable from patient to patient. Although these AGGs were enriched (compared with the ghosts from which they were derived) for heme, as expected, less than 10% of total ghost heme was recovered in them. Remarkably, these AGGs also were enriched for nonheme iron, markedly so in some patients. Iron binding studies showed that the association of free iron with these hemichrome/band 3 AGGs is explained by the fact that free iron binds to denatured hemoglobin. These results document that free iron is nonrandomly associated with the membranes of sickle and beta thalassemic RBCs. Whether this plays a causative role in the premature removal of such cells from the circulation remains to be seen. PMID- 8219210 TI - HRX gene rearrangement in acute lymphoblastic leukemia after adjuvant chemotherapy of breast cancer. PMID- 8219212 TI - American Society of Hematology, 35th Annual Meeting. St. Louis, Missouri, December 3-7, 1993. Abstracts. PMID- 8219211 TI - Graft-versus-host antibody reaction causing a delayed hemolytic anemia after blood transfusion. PMID- 8219213 TI - Hematopoiesis in the aged: a model of hematopoietic dysregulation? PMID- 8219214 TI - Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques. AB - Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro. PMID- 8219215 TI - Allelic loss of IRF1 in myelodysplasia and acute myeloid leukemia: retention of IRF1 on the 5q- chromosome in some patients with the 5q- syndrome. AB - Acquired interstitial deletions of the long arm of chromosome 5 occur frequently in the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Recently IRF1, a putative tumor suppressor gene localized to the long arm of chromosome 5, has been shown to be deleted from the 5q- chromosome in a group of patients with MDS and AML. It has been suggested that the loss of IRF1 may be critical to the development of the 5q- syndrome. We have investigated the allelic loss of IRF1 in a group of 12 patients with MDS and a 5q deletion and 2 patients with AML and a 5q deletion. Gene dosage experiments demonstrated that 12 of 14 patients had loss of one allele of the IRF1 gene but no evidence of homozygous loss and that 2 patients with 5q- syndrome retained both copies of the gene. The retention of IRF1 on the 5q- chromosome in these two cases has been confirmed by fluorescent in situ hybridization localization using an IRF1 cosmid. Pulsed field gel electrophoresis was used to determine whether there was any evidence for structural rearrangement in the region encompassing the IRF1 gene in these two patients. No aberrant bands were detected with a range of rare cutter enzyme digests. We conclude that IRF1 maps outside the commonly deleted segment of the 5q- chromosome and that loss of IRF1 is not solely responsible for the development of the 5q- syndrome. PMID- 8219216 TI - The human MDM-2 oncogene is overexpressed in leukemias. AB - The human homologue of the mouse double minute 2 (MDM-2) gene codes for a cellular protein that forms a complex with the mutant and wild-type p53 protein and modulates its trans-activation activity. Overexpression of the MDM-2 gene in cells increases their tumorigenic potential and overcomes the growth-suppressive activity of p53. Previous reports have shown that the MDM-2 gene is amplified in approximately one third of human sarcomas. To examine the role of MDM-2 in leukemia, we analyzed MDM-2 gene amplification and mRNA expression in various types of leukemias. We did not detect gene amplification in any of the 48 cases of leukemia that we examined. In contrast, we observed significant MDM-2 mRNA overexpression in 34 of 64 cases (53%). The level of mRNA overexpression in some cases of leukemias was comparable to that observed in some cases of sarcomas, which demonstrate more than 50-fold MDM-2 gene amplification. Furthermore, we divided these cases into different prognostic groups according to their karyotypic abnormalities. MDM-2 overexpression seemed to be associated with unfavorable chromosomal abnormalities. These findings suggest that the expression of the MDM-2 gene is altered in a significant fraction of human leukemias and MDM 2 may play a significant role in leukemogenesis. In addition, these results suggest that mechanisms other than gene amplification may play a significant role in deregulating the MDM-2 expression. PMID- 8219217 TI - A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy. AB - Twenty-six patients, whose B-cell lymphoma had relapsed after conventional therapies, were treated in a phase I dose escalation study with an immunotoxin consisting of a mouse CD22 monoclonal antibody (RFB4:IgG1K) coupled to chemically deglycosylated ricin A chain (dgA). Two to 12 doses of the immunotoxin were infused intravenously at 48-hour intervals. The peak serum concentration and half life (T1/2) did not correlate directly with the dose and averaged 3.8 micrograms/mL and 7.8 hours, respectively. The main dose-limiting toxicity was caused by the vascular leak syndrome (VLS) consisting of weight gain, edema, serum albumin decrease, and critically by pulmonary edema. Myalgia occurred frequently and was only dose limiting in one patient who developed rhabdomyolysis. The presence of lymphoma cells in the blood (> or = 10(10)/L) and clinically detectable splenomegaly were associated with reduced toxicity and a shorter T1/2. Nine of 24 evaluable patients (37.5%) made antibody to either mouse Ig or dgA. There were five partial responses (PR) and one complete response (CR) lasting 30 to 78 days. High peak concentrations of immunotoxin in the serum, a long T1/2, and large areas under the curve (AUC) correlated with both clinical response and toxicity. None of three patients with CD5+ lymphomas (including two CLL patients) had more than mild toxicity or responded to the immunotoxin. PMID- 8219218 TI - Binding of membrane-anchored macrophage colony-stimulating factor (M-CSF) to its receptor mediates specific adhesion between stromal cells and M-CSF receptor bearing hematopoietic cells. AB - To explore the biologic significance of the membrane-anchored form of macrophage colony-stimulating factor (M-CSF), we examined whether interaction between membrane-bound M-CSF and its receptor mediates intercellular adhesion as well as cell proliferation and differentiation. Human M-CSF receptors were expressed on a murine interleukin-2 (IL-3)-dependent cell line, FDC-P2, by DNA transfection with the c-fms gene (FDC-P2-MCSFR). A human bone marrow-derived stromal cell line, KM102, was used in the cell adhesion assay. The expression of membrane-bound M CSF on KM102 cells was demonstrated by flow cytometry and immunoblot analysis. After the incubation of parent and transformed FDC-P2 cells on confluent KM102 cells, nonadherent cells were removed and the cells attached to KM102 cells were examined microscopically. Almost all parent FDC-P2 cells were nonadherent, whereas a significant number of FDC-P2-MCSFR cells bound to KM102 cells. The addition of anti-M-CSF or anti-M-CSF receptor neutralizing antibodies dose dependently inhibited the binding of [3H]-thymidine-labeled FDC-P2-MCSFR cells to KM102 cells. An excess amount of M-CSF also inhibited the binding. On the other hand, the addition of antibodies against some representative adhesion molecules (vitronectin receptor, Pgp-1/CD44, and VLA-4) did not inhibit the adhesion between FDC-P2-MCSFR cells and KM102 cells. These results support the idea that membrane-anchored M-CSF and its receptor may function as mediators of cell-cell adhesion. PMID- 8219219 TI - Interferon-gamma antagonizes interleukin-6-induced expression of interleukin-4 receptors in murine myeloid cells by a transcriptional mechanism. AB - The murine myeloid leukemia cell line M1 induced by interleukin-6 (IL-6) is a model system to study the differentiation of blast cells to mature macrophages. We have recently shown that IL-6 induces the expression of the IL-4 receptor (IL 4R) in these cells. In the present study we investigate the mechanism of action of interferon-gamma (IFN-gamma), an antagonist of IL-4 in numerous cells and a cofactor in both induction and suppression of myelopoiesis, on the expression of IL-4R. Flow cytometry shows that IFN-gamma downregulates the IL-6-induced expression of IL-4R whereas it has no such effect on the high-affinity receptors for monomeric IgG2a (Fc gamma RI). As demonstrated by Scatchard analysis, the number of IL-4R decreases by more than 50% after IFN-gamma treatment whereas the receptor affinity remains unchanged. Northern analysis shows that this decrease is paralleled by a decrease in IL-4R mRNA but not Fc gamma RI or lysozyme mRNA. Nuclear run-on analysis shows that IFN-gamma suppresses the IL-6-induced transcription of the IL-4R gene, whereas actinomycin-D chase experiments showed no change of IL-4R mRNA stability. Furthermore, the production of soluble IL-4R protein is suppressed by IFN-gamma as well. These data explain how IL-4R can be modulated by IFN-gamma in myeloid cells and are consistent with the myelosuppressive capacity of IFN-gamma. PMID- 8219220 TI - Enrichment and functional characterization of Sca-1+WGA+, Lin-WGA+, Lin-Sca-1+, and Lin-Sca-1+WGA+ bone marrow cells from mice with an Ly-6a haplotype. AB - Approximately 4% to 5% of all bone marrow (BM) cells and 8% to 9% of low density BM cells from FVB/N and BALB/c mice (Ly-6a haplotype) show high to intermediate expression of Ly-6E.1 antigen, recognized by the Sca-1 antibody. Functional properties of enriched cells expressing Ly-6E.1-allelic form of Sca-1 antigen were analyzed and correlated with the properties of cells expressing the carbohydrate binding sites for the lectin wheat-germ agglutinin (WGA). Using equilibrium density centrifugation and fluorescence-activated cell sorting, Sca 1+WGA+, Lin-WGA+, Lin-Sca-1+, and Lin-Sca-1+WGA+ cells were isolated and their splenic colony-forming unit (CFU-S) cell content, radioprotection ability, and long-term reconstitution capacity determined. Enriched Sca-1+WGA+, Lin-WGA+, Lin Sca-1+ and Lin-Sca-1+WGA+ cells gave rise to 1 CFU-S12 cell out of 26, 20, 21, and 15 sorted cells, respectively. When transplanted into lethally irradiated recipients (100 to 500 cells/mouse) all populations rescued 70% to 100% of recipients in a 30-day radioprotection assay and mediated survival of 40% to 80% of recipients 6 months after transplantation. Using transgenic mice as cell donors we have shown that 12 to 16 weeks after transplantation of 100 Sca-1+WGA+, Lin-WGA+, Lin-Sca-1+, and Lin-Sca-1+WGA+ cells, 40% to 80% of recipients had donor cells in BM, spleen, thymus, and lymph nodes. These results indicate that the population of cells expressing Ly-6E.1 form of Sca-1 antigen in two analyzed mouse strains with Ly-6a haplotype contains CFU-S and long-term repopulating cells. Furthermore, the data suggest that, at least in FVB/N mice, day-12 CFU-S cells and cells with long-term repopulating capacity simultaneously express Ly 6E.1 form of Sca-1 antigen and WGA-binding molecules. PMID- 8219221 TI - Characterization of the interactions between procoagulant albumin and human endothelial cells. AB - Normal human plasma contains procoagulant albumin (PC-Al), an anionic form of albumin that induces tissue factor (TF) activity in human umbilical vein endothelial cells (HUVEC) and monocytes. In this study, we investigated both the interactions between HUVEC and PC-Al and the mechanism by which PC-Al induces TF activity. Binding of PC-Al to HUVEC was specific and reversible. Further studies indicated that membrane-bound PC-Al was not internalized by HUVEC. A potential receptor on HUVEC was suggested by studies in which the capacity of a variety of reagents to inhibit the activity of PC-Al was quantitated. Induction of TF activity by PC-Al was antagonized by dextran sulfate, heparin, fucoidan, and concanavalin A but not by ovalbumin, polyglutamic acid, or polyvinyl sulfate. This competition profile bears similarities to those reported for scavenger receptors that have been identified on both HUVEC and monocytes. Involvement of protein kinase C (PKC) in the PC-Al-induced enhancement of TF activity was suggested by experiments in which staurosporine, an inhibitor of PKC, suppressed the activity of PC-Al. The induction of TF activity by PC-Al was further characterized by using a quantitative polymerase chain reaction assay. Increased TF mRNA was first seen after 1 hour of incubation with PC-Al. Maximal observed expression occurred at 2 hours, but at 5 hours, expression had significantly decreased. Monocytes could also be induced to express TF mRNA after a 2-hour incubation with PC-Al. These results suggest that the functionally relevant binding of PC-Al to HUVEC may be mediated through interactions with a membrane constituent that has some of the properties of a scavenger receptor and that this interaction augments TF activity by enhancing transcription of TF mRNA, at least in part, by a mechanism that is dependent on activation of PKC. PMID- 8219222 TI - Variability of integrin alpha 2 beta 1 activity on human platelets. AB - The activity and surface antigenicity of alpha 2 beta 1 on platelets from 27 normal subjects were found to vary significantly. A fourfold range of surface antigen correlates with a 20-fold variation in the ability of nonactivated, washed platelets to adhere to type I collagen and a fivefold variation in the adhesion of platelets to type III collagen. These differences in surface receptor are reflected in significant variation in the lag time required for type I collagen-induced platelet aggregation in platelet-rich plasma. Among the same individuals, no difference was observed in surface levels or activities of two other platelet integrins, the fibronectin receptor alpha 5 beta 1 and the fibrinogen receptor alpha IIb beta 3. In all cases studied, we observed complimentary differences in the incorporation of 125I into surface alpha 2 beta 1, in quantity of surface alpha 2 beta 1 antigens, and in alpha 2 beta 1 collagen receptor activity. Despite variations in these parameters, there was no difference in the electrophoretic mobility or isoelectric point of either integrin subunit among the individuals studied. The wide range of activity and antigenicity of this platelet collagen receptor may result from polymorphism(s) in the alpha 2 beta 1 genes, or the activity of alpha 2 beta 1 may be variably regulated by another gene product. The heterogeneity of platelet alpha 2 beta 1 that we describe in this report certainly explains previous discrepancies concerning the contributions of this integrin to platelet adhesion to collagens. Most importantly, differences in surface collagen receptor activity may correlate with a long-term risk toward thrombosis, impaired hemostasis, and/or cardiovascular disease. PMID- 8219223 TI - Prostaglandin E2 potentiates platelet aggregation by priming protein kinase C. AB - Prostaglandin E2 (PGE2) is produced by activated platelets and by several other cells, including capillary endothelial cells. PGE2 exerts a dual effect on platelet aggregation: inhibitory, at high, supraphysiologic concentrations, and potentiating, at low concentrations. No information exists on the biochemical mechanisms through which PGE2 exerts its proaggregatory effect on human platelets. We have evaluated the activity of PGE2 on human platelets and have analyzed the second messenger pathways involved. PGE2 (5 to 500 nmol/L) significantly enhanced aggregation induced by subthreshold concentrations of U46619, thrombin, adenosine diphosphate (ADP), and phorbol 12-myristate 13 acetate (PMA) without simultaneously increasing calcium transients. At a high concentration (50 mumol/L), PGE2 inhibited both aggregation and calcium movements. PGE2 (5 to 500 nmol/L) significantly enhanced secretion of beta thromboglobulin (beta TG) and adenosine triphosphate from U46619- and ADP stimulated platelets, but it did not affect platelet shape change. PGE2 also increased the binding of radiolabeled fibrinogen to the platelet surface and increased the phosphorylation of the 47-kD protein in 32P-labeled platelets stimulated with subthreshold doses of U46619. Finally, the amplification of U46619-induced aggregation by PGE2 (500 nmol/L) was abolished by four different protein kinase C (PKC) inhibitors (calphostin C, staurosporine, H7, and TMB8). Our results suggest that PGE2 exerts its facilitating activity on agonist-induced platelet activation by priming PKC to activation by other agonists. PGE2 potentiates platelet activation at concentrations produced by activated platelets and may thus be of pathophysiologic relevance. PMID- 8219224 TI - Acute thrombocytopenic purpura in relation to the use of drugs. AB - The relation of acute thrombocytopenic purpura (TP) to the use of drugs was investigated in a case-control study conducted in eastern Massachusetts, Rhode Island, and the Philadelphia region; 62 cases over the age of 16 years with acute onset and with a rapid recovery were compared with 2,625 hospital controls. After control for confounding by multiple logistic regression, use of the following drugs in the week before the onset of symptoms was significantly associated: trimethoprim/sulfamethoxazole (relative risk [RR] estimate, 124), quinidine/quinine (101), dipyridamole (14), sulfonylureas (4.8), and salicylates (2.6). The overall annual incidence of acute TP was estimated to be 18 cases per million population. The excess risks for the associated drugs were estimated to be 38 cases per million users of trimethoprim/sulfamethoxazole per week, 26 per million for quinidine/quinine, 3.9 per million for dipyridamole, 1.2 per million for sulfonylureas, and 0.4 per million for salicylates. Associations with sulfonamides, quinidine/quinine, sulfonylureas, and salicylates have been previously reported, but the present study has provided the first quantitative measures of the risk. The association with dipyridamole was unexpected. In general, despite large RRs, the incidence rates attributable to the drugs at issue (excess risks) were low, suggesting that TP is not an important consideration in the use of the various drugs. PMID- 8219225 TI - The N-terminal domain of human urokinase receptor contains two distinct regions critical for ligand recognition. AB - The high-affinity receptor that binds human urokinase-type plasminogen activator (hu-PAR) is a glycosyl-phosphatidylinositol (GPI)-anchored cell-surface glycoprotein that belongs to the Ly-6 superfamily of T-cell-activating receptors. Binding of urokinase (u-PA) to u-PAR is species-specific, since neither murine (mu-PAR) nor hu-PAR binds u-PA from the other species. I designed and analyzed a series of exchanges between hu-PAR and mu-PAR in the N-terminal first domain to which ligand-binding function had been independently mapped. Introduction of as few as 13 murine residues (six of 13 variables) into the N-terminal region of hu PAR abrogated binding to recombinant human pro-u-PA, whereas the opposite chimera, a mu-PAR carrying six of 13 human residues, was positive for binding. Within this region, the mu-PAR domain 1 could be minimally humanized to bind human pro-u-PA by a substitution of as few as four of the six nonconserved residues, thereby identifying the residues arginine-2, lysine-7, threonine-8, and glycine-10 as important in determining binding specificity. By alanine-scanning mutagenesis, a second recognition site within domain 1 was discovered between residues 47 and 53, a segment that is fully conserved between the human and the mouse receptors. Taken together, these results provide identification of two confined subregions within the N-terminal domain of hu-PAR critically involved in pro-u-PA recognition. PMID- 8219226 TI - Tumor necrosis factor-dependent production of human immunodeficiency virus 1 in chronically infected HL-60 cells. AB - Tumor necrosis factor (TNF) may play a central role in proviral activation and release from latency in cells infected with the human immunodeficiency virus (HIV). We studied viral production and its relation to TNF in a HL-60 cell line (J22-HL-60) infected with a monocytotropic strain of HIV-1JR-FL. Viral production was stimulated to similar levels by TNF, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Production of the virus was not suppressed by 3'-azido-3'-deoxythymidine (AZT), indicating that viral production was not caused by superinfection. Low concentrations of TNF (0.1 ng/mL) induced viral production with a short lag period of 8 hours, and this proviral activation was specifically suppressed by anti-TNF antibodies. However, induction of virus production by 1,25(OH)2D3 showed an extended lag period of 2 to 3 days. The effect of 1,25(OH)2D3 on virus production was also blocked by anti TNF antibodies, which suggests the direct participation of TNF in this process. TNF accumulated in the culture supernatant of cells stimulated with 1,25(OH)2D3 with a kinetics consistent with its involvement in the action of 1,25(OH)2D3 on viral production. The J22-HL-60 cell line produced low levels of virus when cultured in the absence of an external stimulus; however, this basal viral production was suppressed greater than 80% in the presence of anti-TNF antibodies. Corresponding low levels of TNF were detected in the culture supernatants. Viral production decreased slowly with increasing passage of the cells, and no virus was detected in the supernatants of cells maintained in culture for several months. Concomitantly, TNF was no longer detected in the supernatant of these cells, which suggests that endogenous autocrine production of TNF drives viral production in the unstimulated cells. However, viral production was stimulated in these cells by low concentrations (0.1 ng/mL) of added TNF. These results argue for a central role for TNF in HIV proviral activation in chronically infected myeloid cells. PMID- 8219227 TI - Consensus AP-1 and CRE motifs upstream from the human cytotoxic serine protease B (CSP-B/CGL-1) gene synergize to activate transcription. AB - The human CGL-1/cytotoxic serine protease B gene (CSP-B; also known as granzyme B) is transcriptionally activated during cytotoxic T-lymphocyte maturation. Activation can be mimicked in the PEER T-cell leukemia cell line by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) and N6-2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (bt2cAMP). In this report, we show that a consensus AP 1 element and a consensus cAMP response element (CRE) located 5' to the CSP-B transcriptional start site are both required for transcriptional activation of the CPS-B promoter in TPA + bt2cAMP-stimulated PEER cells. A 94-bp fragment containing both elements activates a heterologous promoter in an orientation independent fashion. Several single nucleotide substitutions in the AP-1 site abolish activity of the 94-bp fragment. Several point mutations in the consensus CRE substantially reduce promoter activity, but one CRE mutation increases activity fourfold. Replacement of the CRE with a second copy of the AP-1 site results in a level of transcriptional activity comparable with that of the wild type sequence, but replacement of the AP-1 site with a CRE abolishes activity. Neither the AP-1 site nor the CRE can be effectively replaced with an SP-1 site. Deletions between the AP-1 site and the CRE retain full activity only if helical spacing is preserved, suggesting that synergism between these two elements is either the result of cooperative binding of factors to the DNA or of cooperative binding of DNA-bound factors to another protein. PMID- 8219228 TI - Suppression of B-cell development as a result of selective expansion of donor T cells during the minor H antigen graft-versus-host reaction. AB - A murine model of bone marrow (BM) transplantation in which donor (B10.D2) and recipient (BALB/c) mice were major histocompatibility complex (MHC) (H-2d) and Mls-1 identical, but incompatible at multiple non-MHC minor histocompatibility (H) antigens, and at Mls-2,3 was used to examine regeneration of B-cell development during the minor H antigen graft-versus-host reaction (GVHR). Mice that received T-cell-depleted allogeneic BM regained significant pre-B cells (sIg 14.8+) in their BM. Mice undergoing GVHR after transplantation with allogeneic BM + T cells had less than 2% pre-B cells in their BM at day 7 and only 12% to 14% pre-B cells at days 21 and 28 compared with greater than 20% pre-B cells in the allogeneic controls. After partial recovery, the pre-B cells in the BM of GVH mice again decreased to less than 3% by day 42. This abnormal pattern of pre-B cell development in mice undergoing GVHR was associated with a reduced response to interleukin-7 (IL-7) in vitro. The delay in B-lineage cell reconstitution in mice with GVHR correlated with the expansion of donor V beta 3+ T cells in both the spleen and BM. BM T cells from mice with GVHR as well as isolated V beta 3+ T cells inhibited IL-7 colony-forming units from normal BM in co-culture assays. This inhibition could be reversed with anti-interferon gamma (IFN gamma) antibody. These data suggest that the delay in appearance and the reduction in proportion and number of pre-B cells observed early during the GVH reaction in this model is caused, in part, by the inhibitory actions of IFN gamma derived from donor V beta 3+ T cells on B-lineage cell development. PMID- 8219229 TI - Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. AB - The contribution of the immune system to healthy aging and longevity is still an open question. For this reason, several immune parameters (T, B, and natural killer [NK] cell subsets; non-major histocompatibility complex [MHC]-restricted cytotoxic activities, ie, natural and redirected killing [RDK] activities) were studied in a total of 138 healthy subjects of different ages, from 4 to 106 years of age, including 26 centenarians. The major age-related modifications were the following: (1) a decrease in the absolute number of T lymphocytes (CD3+), involving both CD4+ and CD8+ subsets, accompanied by a marked concomitant increase in the number of activated T cells (CD3+, HLA-DR+); (2) a marked decrease in the number of B lymphocytes (CD19+); and (3) an increase in the number of cells with markers of NK activity and of T lymphocytes able to mediate non-MHC-restricted cytotoxicity. These modifications linearly progressed with age and centenarians followed the trend, suggesting that their immune system did not escape the aging process. However, other immunohematologic parameters (number of red blood cells, platelets, and leukocytes) and important immune functions, such as cytotoxic activities (NK and RDK cell activities), were well preserved throughout life until the last decades of life. Unexpectedly, in apparently healthy middle-aged subjects, a decrease of cytotoxic activities was observed in comparison with those of both young controls and centenarians. In conclusions, our data suggest that in centenarians some immune responses are kept at a high level of efficiency, likely contributing to their successful aging. However, this selected group of people does not escape the aging process, as shown by the progressive derangement of a variety of immune parameters. PMID- 8219230 TI - Differential regulation of human B-lymphocyte tumor necrosis factor-alpha (TNF alpha) and lymphotoxin (TNF-beta) production by protein phosphatase 1 and 2A inhibitor. AB - Tumor necrosis factor (TNF) and lymphotoxin (LT; TNF-beta) are major cytokines produced by B lymphocytes. Stimulation by okadaic acid, a phosphatase 1 and 2A inhibitor, markedly increased TNF mRNA accumulation and cytokine production. On the other hand, the accumulation of LT mRNA was not affected by okadaic acid despite structural and functional similarities between TNF and LT. The increase in TNF mRNA accumulation was due to the stimulation of gene transcription and a marked stabilization of this mRNA. The binding activities of the transcription factors AP-1 and AP-2 and NF kappa B, which regulates TNF gene transcription, were also stimulated by okadaic acid. In addition, okadaic acid was shown to increase TNF production at the protein level. These results show the importance of protein phosphatases in the regulation of cytokine production in B cells, and further identifies differences in the regulation of TNF-alpha and LT production. PMID- 8219231 TI - Differentiation state and responses to hematopoietic growth factors of murine myeloid cells transformed by myb. AB - Murine hematopoietic cells can be transformed in vitro by recombinant retroviruses that express the myb oncogene, and hematopoietic growth factor (HGF) dependent myeloid cell lines can be derived from these transformed primary cells. In this study, the differentiation state and responses of myb-transformed hematopoietic cells (MTHCs) have been investigated. We find that MTHCs exhibit properties of early myeloid progenitors including synergistic responses to combinations of HGFs and expression of certain surface markers. As reported previously, MTHCs respond well to granulocyte-macrophage colony-stimulating factor (GM-CSF) but can also respond to interleukin-3 (IL-3); the response to the latter factor depends on the mouse strain from which the cells are derived. Although these single factors stimulate MTHCs, combinations of these factors with colony-stimulating factor-1 (CSF-1 or M-CSF) or Steel factor (SLF or SCF) act synergistically to promote colony formation. The surface markers expressed by MTHCs include both granulocyte-macrophage lineage specific antigens Gr-1, 7/4, F4/80, and Mac-1, as well as two antigens found on early progenitors and stem cells--Thy-1 and Sca-1 (Ly6E). Expression of the latter markers is often heterogeneous and can be modulated by the growth factors to which the cells are exposed. Finally, we show that monocytic differentiation of MTHCs can be induced by exposure to tumor necrosis factor (TNF alpha). Taken together, these results suggest that MTHCs will be a useful model for studying HGF/cytokine responses in both proliferation and differentiation. PMID- 8219232 TI - Recombinant human interleukin-4 inhibits growth of some human lung tumor cell lines in vitro and in vivo. AB - Cytokines play an important role in activating the immune system against malignant cells. One of these cytokines, interleukin-4 (IL-4) has entered clinical phase I trials because of its immunoregulatory potency. In the present study we report that recombinant human (rh) IL-4 has major direct antiproliferative effects on one human lung cancer cell line (CCL 185) in vitro as measured by a human tumor cloning assay (HTCA), tritiated thymidine uptake, and counting cell numbers and marginal activity in a second cell line (HTB 56) in the HTCA. This activity could be abolished by neutralizing antibody against rhIL 4. The biological response of the tumor cells to the cytokine is correlated with expression of receptors for human IL-4 on both the mRNA level and the protein level. The responsive cell line, CCL 185, secretes IL-6 after being incubated with rhIL-4. On the other hand, neutralizing antibodies against IL-6 showed no influence on the growth modulatory efficacy of rhIL-4 in this cell line. Furthermore, CCL 185 does not show detectable production of IL-1, tumor necrosis factor alpha or interferon gamma after incubation with rhIL-4. Thus, the response to rhIL-4 is not mediated through autocrine production of these cytokines triggered by rhIL-4. In a next series of experiments some of the cell lines were xenotransplanted to BALB/c nu/nu mice. Subsequently, the mice were treated for 12 days with two doses of 0.5 mg/m2 rhIL-4 or control vehicle subcutaneously per day. Treatment with rhIL-4 yielded a significant inhibition of tumor growth versus control in two of the non-small cell lung cancer cell lines being responsive in vitro (CCL 185, HTB 56). Histology of the tumors in both groups showed no marked infiltration of the tumors with murine hematopoietic and lymphocytic cells consistent with the species specificity of IL-4. In contrast, no tumor growth inhibition was found in the small cell lung cancer cell lines (HTB 119, HTB 120) being nonresponsive in vitro. We conclude that rhIL-4 has direct antiproliferative effects on the growth of some human non-small cell lung cancer cell lines in vitro and in vivo, which together with its regulatory effects on various effector cell populations makes this cytokine an interesting candidate for further investigation in experimental cancer treatment. PMID- 8219233 TI - Stimulation of interleukin-6 and prostaglandin E2 secretion from peritoneal macrophages by polymers of albumin. AB - Interleukin-6 (IL-6) is a multifunctional cytokine that is elevated in vivo during acute infection, chronic inflammation, and some hematopoietic malignancies. To understand how IL-6 becomes elevated in vivo, it is important to identify factors that can stimulate its secretion from effector cells. We found that commercial preparations of bovine serum albumin (BSA) stimulated murine macrophages to secrete high levels of IL-6. In fact, BSA was at least as potent as bacterial lipopolysaccharide (LPS) in stimulating IL-6 production. Stimulation was clearly visible at concentrations as low as 20 micrograms/mL and reached saturation at 0.5 to 1 mg/mL albumin, at which concentration 1.1 x 10(6) oil elicited macrophages produced 6,000 +/- 700 B9 units of IL-6 in an overnight incubation. Prostaglandin E2 production was induced by the same concentrations of BSA. Both resident and oil-elicited peritoneal cells were responsive to the albumin. The stimulatory activity did not derive from contamination of the protein with Escherichia coli LPS; when compared directly with LPS, the response to BSA was more rapid, had a higher amplitude, and was not inhibitable by polymyxin B. In addition, macrophages isolated from C3H/HeJ mice, which have an inherited defect in their ability to respond to LPS, secreted IL-6 in response to BSA but not to LPS. The stimulatory activity was stable to heat, mild acid, and reduction/alkylation and copurified with albumin on Cibachron Blue agarose (Sigma, St Louis, MO) and anti-albumin immunoaffinity chromatography. Comparison of different sources and preparations of albumin showed differences in the levels of IL-6-inducing activity; three different lots of commercial fatty acid-free BSA and one lot of polymer-enhanced BSA stimulated IL-6 secretion by more than 100 fold over basal levels whereas other preparations showed more limited activity. A sample of BSA that was active in vitro caused a marked elevation of IL-6 when injected into BALB/c mice, thus demonstrating inflammatory activity in vivo. When the albumin preparations were fractionated by ion exchange and gel filtration chromatography and then analyzed by sodium dodecyl sulfate-gel electrophoresis and Western blot immunoassay, it was found that the IL-6-inducing activity resided in high molecular weight polymers of albumin. The ability of albumin polymers to stimulate IL-6 production represents a novel mechanism for modulation of this cytokine. PMID- 8219234 TI - New insights suggesting a possible role of a heat shock protein 70-kD family related protein in antigen processing/presentation phenomenon in humans. AB - A possible role of the peptide binding protein (PBP) 72/74 in antigen processing and presentation has been recently suggested in mice. In order to evaluate a possible analogous role of a PBP72/74-related protein in humans, immunoelectron microscope investigations, functional studies, and immunofluorescence analyses were performed on normal human peripheral antigen-presenting cells. We demonstrated that the determinant recognized by antiheat shock protein (HSP) 72/73 monoclonal antibody (MoAb) is constitutively expressed on the cell surface of monocytes as well as of B cells. Moreover, the capability of monocytes to present a recall antigen to T cells was significantly decreased when preincubated with an anti-HSP72/73 MoAb. These data add further strength to a potential role of a protein related to human PBP72/74 homologue in antigen processing and/or presentation. Finally, the capability of anti-HSP72/73 MoAb to impair the ability of fixed monocytes to present a synthetic peptide demonstrates that cell surface localized PBP72/74-related protein could play a role in antigen presentation. PMID- 8219235 TI - Expression of a functional laminin receptor (alpha 6 beta 1, very late activation antigen-6) on human eosinophils. AB - The mechanisms responsible for the accumulation of eosinophils at sites of allergic and other inflammatory reactions are unknown, but recent studies have implicated both eosinophil and endothelial adhesion molecules in this process. However, less well studied have been the adhesive interactions between eosinophils and the subendothelial basement membrane and interstitial connective tissues. To test the hypothesis that eosinophils might interact with extracellular matrix proteins, we analyzed purified human eosinophils for the expression and function of various beta 1 integrins. Using indirect immunofluorescence and flow cytometry, purified eosinophils from mildly allergic donors were found to consistently express the integrin subunits beta 1 (CD29), alpha 4 (CD49d, very late activation antigen [VLA]-4 alpha), and alpha 6 (CD49f, VLA-6 alpha). No significant expression of the alpha 1, alpha 2, alpha 3, alpha 5, or beta 4 subunits was detected. Platelet contamination of the eosinophil preparations was excluded by light microscopy and by the inability to detect expression of platelet glycoproteins alpha v, CD41b, and CD42b. Immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of eosinophils confirmed the expression of cell-surface beta 1, alpha 4, and alpha 6. Furthermore, eosinophils purified from allergic donors were shown to adhere to plate-bound laminin, but not to type 1 or type 4 collagen. Adhesion to laminin was concentration-dependent, required divalent cations, and was completely and specifically inhibited by the anti-alpha 6 monoclonal antibody (MoAb) GoH3 and by the anti-beta 1 MoAb 33B6. Interestingly, the anti-beta 1 MoAb 18D3 (which like 33B6 blocks eosinophil binding to VCAM-1) did not inhibit eosinophil adhesion to laminin, suggesting that there are functionally distinct epitopes on the beta 1 subunit. Eosinophils purified from 4 healthy, nonallergic donors also showed alpha 6-dependent adhesion to laminin, although these cells adhered less well. These studies establish the expression of alpha 6 beta 1 on human eosinophils and document its function as a laminin receptor. Interaction of eosinophil alpha 6 beta 1 with laminin, eg, in basement membranes, may contribute to the localization of these cells at inflammatory sites in vivo. PMID- 8219236 TI - Proteoglycan metabolism in normal and inflammatory human macrophages. AB - To study proteoglycan metabolism in inflammatory macrophages, primary cultures of human macrophages were cultured in the absence and presence of bacterial lipopolysaccharide (LPS). When exposed to [35S]sulfate, the cells incorporated the label almost exclusively into chondroitin sulfate proteoglycan (CSPG), which was recovered from the culture medium and the cell layer. Cells stimulated with LPS secreted approximately three times more [35]CSPG into the culture medium than control cells. Furthermore, cell adhesion was also found to promote proteoglycan secretion; when nonadherent monocytic cells were induced to adhere, the release of proteoglycan increased two times. The increased secretion seen in LPS stimulated macrophages was partly due to increased biosynthesis, but was mostly due to increased sorting of CSPG to the secretory pathway. Only about 20% of the CSPG synthesized in unstimulated cells was secreted, whereas the corresponding figure in LPS-treated cells was 35%. In both cell types, the remaining [35S]CSPG was degraded, probably in the lysosomes. The degradation was a two-step process. First, the [35S]CSPG was rapidly cleaved to yield free glycosaminoglycan (GAG) chains (t1/2 = 15 to 30 minutes). Secondly, the GAG chains were completely depolymerized (t1/2 = 2 to 3 hours). Neither resting nor LPS-stimulated cells sorted CSPG to intracellular storage, as is evident in many hematopoietic cells. The LPS-treated cells synthesized [35S]CSPG of smaller molecular size than did control cells, with GAG chains of approximate molecular mass of 12 kD versus 16 kD in control cells. No difference was seen in the disaccharide composition of the GAG chains; both LPS-stimulated and unstimulated cells expressed a mixture of 80% to 90% chondroitin 4-sulfate and 10% to 20% chondroitin 4,6-disulfate. N terminal sequence and Northern blot analysis indicate that the core protein of the CSPG secreted by human macrophages is serglycin. PMID- 8219237 TI - Stimulation of the human neutrophil respiratory burst by formyl peptides is primed by a protein kinase inhibitor, staurosporine. AB - Stimulation of polymorphonuclear neutrophils (PMN) by phorbol esters or formyl peptides (fMLP) generates large quantities of superoxide anion, the so-called respiratory burst (RB), a phenomenon associated with intense phosphorylation of a 47-kD protein (p47 phox). Staurosporine, a potent protein kinase C (PKC) antagonist, inhibits both responses when PMN are stimulated by phorbol myristate acetate (PMA), suggesting a positive role of PKC. In this study, we reassessed these PMN responses in fMLP-stimulated cells and found that staurosporine had opposite effects depending on the duration of PMN treatment with staurosporine. Short PMN incubation (0.5 to 3 minutes) with 25 to 100 nmol/L staurosporine inhibited the fMLP-induced RB, whereas longer treatment (15 to 20 minutes) enhanced it by up to about 200% relative to controls. In contrast, the PMA mediated RB was depressed by staurosporine in a time-dependent manner. A primed fMLP-induced RB was also observed after long (15 minutes) PMN treatment with 5 to 100 mumol/L H-7, whereas shorter treatment (5 minutes) resulted in a small decrease in RB. By contrast, the tyrosine kinase inhibitor genistein (2 to 80 mumol/L) depressed fMLP-induced RB whatever the duration of PMN treatment. Analysis of 32P-phosphorylated proteins in fMLP-stimulated cells showed that short PMN treatment (< 8 minutes) with staurosporine abolished the phosphorylation of the 47-kD protein, which was identified as p47 phox, whereas long treatment partially restored p47 phox phosphorylation up to approximately 50% of the control value. In PMA-stimulated PMN, phosphorylation was reduced in a time-dependent manner. Furthermore, the staurosporine-primed RB and the staurosporine-induced recovery of phosphorylation were inhibited by sphingosine but not by genistein. Thus, in addition to its known depressive effect, staurosporine markedly potentiated fMLP-stimulated RB as a function of the duration of PMN treatment. The restoration of p47 phox phosphorylation suggests that staurosporine may alter the interactions between different protein kinases, producing marked time-dependent changes in signalling pathways. These data emphasize the care that should be taken in interpreting data obtained using this kinase inhibitor that may, however, be helpful analyzing in signalling pathways. PMID- 8219238 TI - Analysis of the human zeta-globin gene promoter in transgenic mice. AB - zeta-Globin is the embryonic form of the alpha chain of hemoglobin. Transgenic mice generated with zeta-globin constructs containing the zeta-globin gene, 557 bp of 5' flanking sequence, and 2-kb of 3' flanking sequence linked to the beta globin locus control region hypersensitive site 2 (HS2) expressed human zeta globin only in embryonic yolk sac erythroid tissue, and not in definitive erythroid tissue in the fetal liver or in adult peripheral blood. To determine what sequences in the 5' flanking region of the zeta-globin gene might be important for developmental specificity, a series of 5' deletion constructs of the zeta-globin gene were made and used to generate transgenic mice. The 5' ends of these constructs were located 417, 207, and 128 bp 5' to the zeta-globin transcriptional start site, and HS2 was included to increase the level of erythroid-specific expression. In all lines of mice tested, human zeta-globin was expressed only in embryonic tissue, and not in fetal livers or in adult peripheral blood. Expression was independent of copy number and appeared to be dependent on the site of transgene insertion. These data suggest that the proximal 128 bp of the zeta-globin promoter is sufficient to properly regulate zeta-globin expression during development. PMID- 8219239 TI - Complete nucleotide sequence of the murine erythroid beta-spectrin cDNA and tissue-specific expression in normal and jaundiced mice. AB - Spectrin, a heterodimer of alpha and beta subunits, is an essential component of the red blood cell membrane skeleton. The jaundiced (ja/ja) mutation causes a severe hemolytic anemia in mice and is mapped to the erythroid beta-spectrin locus (Spnb-1) on chromosome 12. As a prerequisite for determining the molecular defect of the jaundiced mutation, we have cloned and sequenced the complete murine reticulocyte cDNA for normal Spnb-1. Two unique transcripts that differ in the placement of polyA tails are represented in the clones isolated. Amino acid sequence comparison between erythroid and murine brain spectrin (Spnb-2, chromosome 11) shows 67% identity throughout repeats 16 and 17 and complete divergence in domain III, which is associated with the alpha/beta subunit dimerization and phosphorylation. We examined the tissue distribution of normal and mutant erythroid beta-spectrin transcripts using domain-specific probes. Transcripts are detected in normal spleen tissue and reticulocytes (8 and 9.6 kb), brain tissue (10 and 11 kb), skeletal muscle tissue, and cardiac muscle tissue (11, 10.3, 7.2, and 4.0 kb). Extensive variability in mRNA processing is shown with region-specific probes. Steady state levels of the mutant transcripts are reduced when hybridized with a probe to repeats 2 through 6 with the exception of the 7.2-kb transcript that is unique to heart and skeletal muscle tissues, and is present at normal and elevated levels, respectively, in ja/ja mice. These results provide evidence for more diverse tissue-specific products of the Spnb-1 gene than were previously suspected. PMID- 8219240 TI - Analysis of Lewis fucosyltransferase genes from the human gastric mucosa of Lewis positive and -negative individuals. AB - The expression of Lewis fucosyltransferase (FT) mRNA was examined in gastric mucosa from two Lewis-positive [Le(+)] and two Lewis-negative [Le(-)] individuals. Northern blot analysis demonstrated that levels of mRNA were similar in both Le(+) and Le(-) gastric mucosa. We isolated the protein-coding region of the Lewis FT cDNA from Le(+) and Le(-) gastric mucosa by polymerase chain reaction (PCR) amplification. The sequence of cDNA from the Le(-) gastric mucosa shows two single-base substitutions of G for T at position 59 and of A for G at position 508 from the A of the initiation codon of cDNA. These substitutions may be the cause of changes in two amino acid residues, Arg for Leu at position 20 and Ser for Gly at position 170 from the N-terminal. To determine whether either or both of these base substitutions is responsible for the Le(-) gene, we constructed chimera cDNAs and expressed them in COS cells. Those COS cells transfected with a chimera cDNA containing a mutation of the 508th nucleotide did not express Lewis antigen, whereas those cells transfected with a chimera cDNA containing the 59th nucleotide mutation expressed Lewis antigen, indicating that a single-base change from G to A at position 508 is responsible for the Le(-) gene. The G to A transition at position 508 created a new site for PvuII endonuclease. The digestion by PvuII endonuclease of PCR products between the 386th and 612th nucleotides of Lewis FT cDNA from one of the Le(-) individuals proved to be homozygous for the PvuII site. However, the other Le(-) individual was heterozygous for the PvuII site, suggesting the presence of other Le(-) allele(s). Thus, we isolated one of the silent Lewis genes (le). PMID- 8219241 TI - Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission. AB - Ninety-nine consecutive patients with acute leukemia in first complete remission under age 50 (median age 27 years; age range 1 to 47 years) with a histocompatible sibling donor were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation. Sixty-one patients were diagnosed with acute myelogenous leukemia (AML), 34 patients with acute lymphoblastic leukemia (ALL), 3 patients with biphenotypic acute leukemia, and 1 patient with acute undifferentiated leukemia. Thirty of the 34 patients with ALL had at least one of the following high-risk factors: age greater than 30, white blood cell count at presentation > 25,000/microL, extramedullary disease, certain chromosomal translocations, or the need for greater than 4 weeks of induction chemotherapy to achieve first complete remission. Cumulative probabilities of disease-free survival and relapse at 3 years were 61% and 12%, respectively, for the 61 patients with AML and 64% and 12%, respectively, for the 34 patients with ALL. By stepwise Cox regression analysis, significant prognostic variables for patients with acute myelogenous leukemia were the presence of acute graft-versus-host disease and increasing age, whereas for patients with acute lymphoblastic leukemia, significant variables were age and the development of cytomegalovirus associated interstitial pneumonia. Complications related to graft-versus-host disease and relapse of leukemia were the major causes of death. PMID- 8219242 TI - Rapid recovery of platelet function after cardiopulmonary bypass. PMID- 8219243 TI - Thromboembolic disease and human immunodeficiency virus infection. PMID- 8219244 TI - Waldenstrom macroglobulinemia: a role of HCV infection? PMID- 8219245 TI - An introduction to the concepts and classifications of the international classification of impairments, disabilities, and handicaps. AB - This paper aims to introduce the International Classification of Impairments, Disabilities, and Handicaps (ICIDH) and to set the scene for the forthcoming revision process. The consequences of diseases and disorders at the level of the body (impairment), the person (disability), and the person as a social being (handicap) are defined and described. Bearing in mind some of the controversies and confusions which have become apparent in attempts to apply the ICIDH since its publication in 1980, the distinctions between the different concepts are explored: namely, impairment--disability; impairment--functional limitation- disability; and between disability--handicap. The nature of the classification schemes for these concepts is described, together with some implications for methods of assessment. Finally, the contribution the ICIDH has made, and its potential uses are briefly reviewed. PMID- 8219246 TI - Community-based rehabilitation: does it change community attitudes towards people with disability? AB - To achieve the goal of 'Health for All by the Year 2000' the World Health Organization (WHO) adopted an approach to rehabilitation described as community based rehabilitation (CBR). A major objective of CBR is to develop positive community attitudes towards people with disabilities. To determine whether this objective can be achieved, post hoc measurement of attitudes towards people with disabilities was carried out in a community in which CBR had been established and in a control community. It is shown that both groups exhibited neutral attitudes. The community exposed to CBR obtained a mean attitude score significantly (p < 0.001) closer to the positive end of the scale than did the control community. It is concluded that communities in which CBR is being carried out develop more favourable attitudes towards people with disabilities than do those in which no such programme has been implemented. PMID- 8219247 TI - Ability or disability? A study of the functional outcome of 65 consecutive lower limb amputees treated at the Royal South Sydney Hospital in 1988-1989. AB - A follow-up study by personal interview (45) or written response (4) or next-of kin (3) interview using a questionnaire, has been made at least 1 year from discharge of the 52 survivors (82%) of 65 lower limb amputees treated at the Royal South Sydney Hospital in the years 1988-1989. At follow-up prostheses were used by 94% of the people, 72% of the group using their prostheses all day. Independence in self-care was found to be more important to final discharge home than walking skills. The 93% return home rate was considered to be in part due to funding for home modifications provided by government sources. Car driving was a mobility aid for 25% of patients whereas public transport was used by only 9% of subjects. Some patients mentioned that the loss of pain and a feeling of well being was a positive gain from their amputation surgery. PMID- 8219248 TI - Patients' fall records as an aid in designing and assessing therapy in Parkinsonism. AB - Performance of Parkinson patients in a laboratory setting often gives little indication of their real-life behaviour. This is particularly the case for patients who fall. Two such patients were asked to record the time and location of every fall on maps of their apartments before and during their participation in a trial of physiotherapy designed to improve mobility. These fall diaries provided both valuable insight for understanding and addressing their problems and documentation of decreased falling following therapy. PMID- 8219249 TI - Mechanisms of hormone resistance in breast cancer. AB - At least half of all advanced breast cancers are positive for estrogen receptor (ER) and progesterone receptor (PR), but many nevertheless fail to respond to endocrine therapy. Studies of breast cancer cell lines and breast tumor specimens are beginning to reveal molecular heterogeneity of the receptors in subpopulations of these cells, leading to altered receptor function and sometimes to hormone resistance. Here we will review the data on molecular and cellular heterogeneity involving ER and PR, and possible underlying mechanisms of resistance to tamoxifen and progestins. PMID- 8219250 TI - Action of "pure" antiestrogens in inhibiting estrogen receptor action. AB - The mechanism of action of the pure antiestrogens ICI 164384 and ICI 182780 has been investigated. Both antagonists are steroidal antiestrogens with 7 alpha alkylamide side-chains. The antiestrogens reduce the cellular content of the estrogen receptor by reducing the half-life of the protein. A potential mechanism for this effect is suggested by the observation that the DNA binding activity of receptors which have been over-expressed in cells was inhibited in vitro. The inhibitory activity of analogues of ICI 164384 with different side chain lengths correlates with their ability to function as pure antiestrogens in vivo. Since the estrogen binding site overlaps with residues involved in dimerisation, the antiestrogens are likely to bind to a similar site and may therefore with receptor dimerisation in the hormone binding domain by means of the 7 alpha side chain. We propose that the increased turnover of the receptor in the presence of ICI 164384 and ICI 182380 is a consequence of impaired dimerisation of the proteins. PMID- 8219251 TI - A model to describe how a point mutation of the estrogen receptor alters the structure-function relationship of antiestrogens. AB - The antiestrogen tamoxifen [(Z)-1(p-beta-dimethylamino-ethoxyphenyl)-1,2- diphenylbut-1-ene] is an effective anticancer agent for the treatment of hormone responsive breast cancer. Previous studies have demonstrated that a point mutation in the estrogen receptor (ER) resulted in an alteration of the pharmacology of 4-hydroxytamoxifen, the active metabolite of tamoxifen (Jiang et al, Mol Endocrinol 6:2167-2174, 1992). We have extended our studies to evaluate the effect of a point mutation, a Val substitution for Gly at amino acid 400 in the ligand binding domain of ER, on the pharmacology of other antiestrogens in ER stable transfectants derived from the ER-negative breast cancer cell line MDA-MB 231 CL10A. The compounds were tested with or without estradiol-17 beta (E2) for their effects on cell growth in cells expressing the wild type ER (S30) or the mutant ER (ML alpha 2H) or in control antisense ER transfectant AS23 which does not express ER protein. MCF-7 cells, which express the wild type ER, were also used as a control. The growth of AS23 cells was not affected by any of the compounds at a concentration of 1 microM. E2 stimulated the growth of MCF-7 cells but inhibited the growth of ER transfectants S30 and ML alpha 2H. The ML alpha 2H cells were about 10 to 100-fold less sensitive to E2 and antiestrogens than S30 and MCF-7 cells. Keoxifene, an antiestrogen with a high affinity for the ER, maintained antiestrogenic activities in both ER transfectants and MCF-7 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219252 TI - Investigation of the origin of variant, truncated estrogen receptor-like mRNAs identified in some human breast cancer biopsy samples. AB - Variant, smaller sized, estrogen receptor-like mRNAs have been previously cloned and sequenced from human breast cancer biopsy samples. In this study we have found that one variant estrogen receptor-like mRNA, clone 24, which is expressed in only one tumor, consists of sequences from the normal ER gene which is found on chromosome 6 and sequences unrelated to the ER which are found normally on chromosome 12. A more commonly occurring variant estrogen receptor-like mRNA, clone 4, contains sequences from the normal ER gene and LINE-1 sequences. Similar but not identical LINE-1 sequences have been found in some of the intervening sequences of the normal ER gene. The generation of these transcripts may involve either alternative splicing or trans-splicing mechanisms. PMID- 8219253 TI - Exon skipping gives rise to alternatively spliced forms of the estrogen receptor in breast tumor cells. AB - We have previously described three messenger RNA variants coding for the human estrogen receptor (ER) [1]. These variants were identified using the polymerase chain reaction to perform directed cloning of ER cDNAs synthesized from polyadenylated RNA extracted from the human breast cancer cell line T47D. Each of the variants is characterized by the precise deletion of a single exon within the protein coding region of this message and was presumably derived by inaccurate or promiscuous splicing of primary estrogen receptor transcripts. We report here the results of RNAse protection experiments which independently confirm the existence of these splicing variants in T47D cells. Similar analysis of RNA from MCF-7 cells also revealed the presence of variant ER transcripts, suggesting that they may be a common finding in tumor cell lines which express the estrogen receptor. However, attempts to identify splicing variants in a number of nominally ER negative cell lines using either RNAse protection or PCR amplification were without success. PMID- 8219254 TI - An estrogen receptor genetic polymorphism and a history of spontaneous abortion- correlation in women with estrogen receptor positive breast cancer but not in women with estrogen receptor negative breast cancer or in women without cancer. AB - We previously identified a polymorphism in the human estrogen receptor gene. In a preliminary study on women with estrogen receptor positive (ER+) breast tumors, we found that the presence of the rarer of the two alleles, the B' allele, is correlated with a history of spontaneous abortion. Because that study evaluated only women with estrogen receptor positive (ER+) breast cancer, it was unknown whether the observed correlation was restricted to the cancer group or was independent of breast cancer. We have now extended our analysis to include not only additional women with ER+ breast cancer, but also those with estrogen receptor negative (ER-) breast cancer and women without cancer. Results of the current study continue to show an association between the B' allele and a history of spontaneous abortion in the ER+ breast cancer group. There was no such correlation either in the ER- breast cancer group or in the group without cancer. Also, we continue to observe, in the ER+ breast cancer group, a significantly higher concentration of ER protein in tumors from homozygous wild type women (genotype BB), than in the tumors from women who are heterozygous for the rarer allele (genotype BB'). We conclude that the combination of spontaneous abortion and the BB' ER genotype may be a marker for breast cancer susceptibility. PMID- 8219255 TI - Human breast tumors containing non-DNA-binding immunoreactive (67 kDa) estrogen receptor. AB - Evidence to date indicates that structurally abnormal estrogen receptor (variant ER) can be detected in some human breast tumors. Based on in vitro ability to bind DNA sequences containing the cognate estrogen response element (ERE), these variant receptors may be categorized into DNA-binding ER (Type-1 variants) and non-DNA-binding ER (Type-2 variants). To look for Type-2 variants of normal size (67 kDa ER) that lack the ability to form immunoreactive ER-ERE complexes, a panel of 40 cryopreserved primary breast tumors were extracted and analyzed by enzyme immunoassay (ER-EIA), gel-shift, and Western blot techniques. For the 33 tumor extracts containing > or = 10 fmol/mg ER (by ER-EIA), the amount of 67 kDa ER detectable by D75 anti-ER monoclonal antibody under fully denatured and reduced assay conditions (Western blotting) did not correlate well with the presence or intensity of D75 immunoreactive ER-ERE bands seen under native conditions by gel-shift assay. Overall, 30% (10 of 33) of these extracts containing 67 kDa ER failed to produce immunoreactive ER-ERE complexes, with this frequency varying from over 40% in tumor samples with lower ER content (10-49 fmol/mg) to 11% in tumor samples with the highest ER content (> 100 fmol/mg). These results indicate that Type-2 variant receptors characterized as non-DNA binding 67 kDa ER may be present in a significant fraction of ER-positive primary breast tumors; preliminary evidence suggests that further study of abnormalities in ER tertiary or quaternary structure, such as those produced by intracellular oxidation of ER thiol groups, is warranted. PMID- 8219256 TI - The ER-positive/PgR-negative breast cancer phenotype is not associated with mutations within the DNA binding domain. AB - We have used in vitro DNA binding assays as a measure of estrogen receptor (ER) function in human breast tumors. We found that the majority of ER+ (25 ER+/progesterone receptor [PgR]+, and 25 ER+/PgR-) tumors we examined were capable of binding consensus estrogen response element (ERE) oligonucleotides in this assay system. We found significant proteolytic activity in many of the tumors such that protease inhibitors were found to be essential during the preparation of tumor extracts. We next applied direct sequence analysis of the ER DNA binding domain of several of these tumors, and determined that the ER+/PgR- breast tumors did not contain mutations within the DNA binding domain which might explain their apparent discordant receptor phenotype. We did identify an alternatively spliced ER variant missing exon 3 of the DNA binding domain. This variant was unable to function as a transcriptional inducer of an estrogen responsive reporter in a yeast assay system. Furthermore, the exon 3 ER deletion variant was expressed at equivalent levels in all of the ER+ breast tumors, so that it does not appear to be involved in the evolution of the ER+/PgR- breast cancer phenotype. PMID- 8219257 TI - Leucocyte count, proteinuria and smoking in type 1 diabetes mellitus. AB - A case-control study was carried out to analyse leucocyte counts in relation to proteinuria and smoking in type 1 (insulin-dependent) diabetes. The subjects were 180 smoking (87 women, age 32 +/- 11 years, diabetes duration 14 +/- 6 years) and 188 nonsmoking (88 women, age 32 +/- 11 years, diabetes duration, 14 +/- 6 years) type 1 diabetic patients. Leucocyte counts were higher in smokers than in nonsmokers, both in women (7.6 +/- 2.3 vs 6.8 +/- 1.9 x 10(9)/l, P < 0.01) and in men (8.1 +/- 2.7 vs 6.4 +/- 2.0 x 10(9)/l, P < 0.0001). Leucocyte counts correlated with the number of cigarettes smoked per day (r = 0.32, P < 0.0001), but were unrelated to glycosylated haemoglobin levels. Among nonsmokers, leucocyte counts were comparable between patients with normal proteinuria (6.7 +/ 2.2 x 10(9)/l, n = 106), microproteinuria (6.3 +/- 1.7 x 10(9)/l, n = 66) and macroproteinuria (6.8 +/- 1.1 x 10(9)/l, n = 16). Among smokers, patients with macroproteinuria or microproteinuria had higher leucocyte counts than those with normal proteinuria [8.9 +/- 3.0 x 10(9)/l, (n = 36) vs 8.4 +/- 2.7 x 10(9)/l (n = 61) vs 7.0 +/- 1.9 x 10(9)/l (n = 83); P < 0.0001)], a finding which was not due to differences in the number of cigarettes smoked per day. It is concluded that in these type 1 diabetic patients leucocyte counts were higher in smokers than in nonsmokers. Among nonsmokers leucocyte counts were comparable between patients with normal proteinuria and increased proteinuria, whereas among smokers leucocyte counts were higher in patients with increased proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219258 TI - Acute metabolic actions of des-(B27-B30)-insulin and related analogues in adult rats. AB - Metabolic potencies of the destetrapeptide insulin analogues des-(B27-B30) insulin, des-(B27-B30)-insulin-B26-amide, [ThrB26] des-(B27-B30)-insulin-B26 amide and [GluB26] des-(B27-B30)-insulin-B26-amide were studied in anaesthetized adult rats and in primary cultures of rat hepatocytes and compared with that of the native hormone. Hypoglycaemic effects following intravenous bolus injection of insulin or analogues were similar, as were the stimulatory actions on total body glucose disposal during euglycaemic clamping. In these latter studies a maximal stimulation in the range 16-20 mg glucose/kg per hour was observed and identical half-maximally effective serum concentrations for all peptides of about 1 pmol/ml were obtained. Analogue actions on individual peripheral tissues estimated by the uptake of 2-deoxyglucose were not different from those of insulin. In hepatocyte cultures the stimulatory action of destetrapeptide analogues on glycogenesis and on aminoisobutyric acid transport was indistinguishable from that of native insulin, with identical half-maximally effective concentrations. These data demonstrate that des-(B27-B30)-insulin and related destetrapeptide analogues have high biological activity. Since the truncated non-amidated analogue appeared to be monomeric in solution, this peptide could be a candidate for an insulin preparation potentially showing rapid absorption from subcutaneous tissue. PMID- 8219260 TI - Enhancement of the gluconeogenic flux of hepatic glycogen repletion by a phenacyl imidazolium compound in vivo. AB - The effect of a phenacyl imidazolium compound (LY177507 or Proglycosyn, Eli Lilly) on the direct (glucose-->glucose-6-phosphate-->glycogen) and indirect (three-carbon compounds-->glucose-6-phosphate-->glycogen) pathways of liver glycogen synthesis was studied in conscious rats. [1-13C]Glucose (99% enriched) was infused intraduodenally into chronically catheterized Proglycosyn-treated (n = 7) and saline-treated (n = 7) rats for 120 min. Net hepatic glycogen synthetic rates were increased twofold in drug-treated rats compared with saline-treated controls. The percentage of liver glycogen synthesized by the direct pathway was calculated by comparing the 13C isotopic enrichment in the C1 and C6 positions of hepatic glycogen and plasma glucose using 13C nuclear magnetic resonance spectroscopy and gas chromatography-mass spectroscopy techniques and was found to be 59 +/- 5% and 39 +/- 2% (P < 0.05) in the saline treated and Proglycosyn treated groups, respectively. Net flux rates for the direct and indirect pathways were calculated to be 0.24 +/- 0.04 and 0.17 +/- 0.03 mumol/g liver per min, respectively, in the saline-treated group and 0.30 +/- 0.04 (P = NS) and 0.46 +/- 0.06 (P < 0.05) mumol/g liver per min, respectively, in the Proglycosyn-treated group. Thus, Proglycosyn increases net hepatic glycogen synthesis in vivo exclusively through augmentation of the indirect pathway. PMID- 8219259 TI - Type 1 diabetes mellitus: an imbalance between effector and regulatory T cells? AB - Abundant evidence now exists that autoimmunity plays a critical role in the pathogenesis of type 1 (insulin-dependent) diabetes mellitus. The non-obese diabetic (NOD) mouse is an extensively studied animal model of this T-cell mediated autoimmune disease. Our laboratory has focused on isolating diabetogenic T cell clones from NOD mice as a means of elucidating the pathogenesis of type 1 diabetes. This experimental approach presupposes that type 1 diabetes in NOD mice results from the action of islet-reactive T cells that are not present in other mouse strains; the diabetogenic T cells would therefore represent "forbidden clones" which exist in NOD mice as a result of a failure of clonal deletion. While the inappropriate presence of diabetogenic T cells probably plays a central role in murine diabetes, it cannot explain all aspects of the disease. Type 1 diabetes is a chronic disorder with a lengthy preclinical stage; if the diabetogenic T cells acted in an unopposed fashion, one might expect to see a much more fulminant clinical course. This observation suggests that regulatory influences are likely to exist in this disease--a possibility supported by recent experimental data. If these regulatory influences could be identified and enhanced, specific immunotherapy for type 1 diabetes could be achieved. PMID- 8219261 TI - Glucose transporter gene expression in rat conceptus during early organogenesis and exposure to insulin-induced hypoglycemic serum. AB - We investigated the glucose transporter gene and protein expression during early organogenesis in the rat and in rat embryos cultured with hypoglycemic serum. Erythrocyte-type glucose transporter (GLUT-1) mRNA was expressed at a high level in embryos; peak levels were reached at days 10.5-11.5 and decreased as gestational age increased. In contrast, the insulin regulatable glucose transporter (GLUT-4) mRNA was not detected. The levels of GLUT-1 protein determined by Western blot analysis increased in parallel with expression of the glucose transporter (GLUT-1) gene and peak levels were observed on days 10.5 and 11.5, which correspond to the main periods of neural tube formation. Immunohistochemical staining of the embryo on day 10.5 showed that GLUT-1 protein was abundantly located in the tissue of neural tube. When embryos were cultured from day 9.5 to day 10.5 with insulin-induced hypoglycemic serum containing 2-3 mM glucose an increased frequency of anterior neural tube defects was observed in association with a significant reduction of the glycolytic flux. Increased levels of GLUT-1 mRNA and protein were not observed during the culture with hypoglycemic serum compared with the levels in embryos cultured in normal serum. Addition of insulin to normal serum (500 microU/ml) did not affect the GLUT-1 mRNA and protein levels. GLUT-1 mRNA and protein are strongly expressed in the embryo during early organogenesis, especially in the tissues of the neural tube, and the expression of the glucose transporter did not increase in response to prolonged glycopenia. This may account for the vulnerability of embryogenesis to hypoglycemia during these critical developmental periods. PMID- 8219263 TI - The effect of acarbose on the intestinal metabolism of glucose in vitro. AB - The effect of acarbose on the intestinal metabolism of glucose was investigated using an in vitro perfused preparation of the isolated rat small intestine pancreas. In preparations perfused without intraluminal sucrose administration, the total glucose recovered in the portal effluent and the portal values of lactate, pyruvate and alanine did not depend on whether or not acarbose [1.5 mg/kg body weight (b.w.)] was present in the intestinal lumen. The intestinal glucose and lactate contents were very low at the end of the experiment, and identical with or without acarbose. Insulin and glucagon concentrations remained constant during the whole perfusion period. After intraluminal administration of sucrose a clear increase in portal glucose concentration was observed, which was severely reduced by acarbose administration no changes in portal levels of lactate, pyruvate, alanine, insulin and glucagon were observed. The intestinal content of sucrose at the end of the study was significantly higher in the presence of acarbose (1.5 mg/kg b.w.), while the glucose concentration was low both with and without acarbose (0.20 +/- 0.08 vs 0.29 +/- 0.09 mmol/l respectively). These results suggest that acarbose does not influence the metabolic utilization of the glucose being translocated from the lumen. PMID- 8219262 TI - Cross-sectional study of peripheral microcirculation in diabetic patients with microangiopathy: influence of pancreatic and kidney transplantation. AB - Diabetic vascular lesions and peripheral autonomic neuropathy are both closely linked to long-term metabolic control of diabetes. Transcutaneous oxygen tension (PtcO2) measurements were made to elucidate whether autonomic neuropathy disturbs the cutaneous microcirculatory blood flow, and whether long-term glucose normalization ameliorates such impairment. Twenty-eight type 1 (insulin dependent) diabetic patients in whom clinically significant macroangiopathy had been excluded by angiography were studied, subdivided into group A (n = 14; before simultaneous pancreas/kidney transplantation (SPKT); mean age 35 years, range 22-51 years; mean duration of diabetes 24 years, (range 15-32) years and group B (n = 14; mean 31 months, range 2-101 months, after successful SPKT; mean age 35 years, range 19-56 years; mean duration of diabetes 22 years, range 14-29 years). On addition there was a group (group C) of age- and sex-matched healthy control subjects (n = 14; mean age 35 years, range 23-62 years). PtcO2 measurements included basal recordings at 44 degrees C on the leg and the foot, functional recordings at 44 degrees C after arterial occlusion of the limb for 4 min, measurements during breathing 5 l oxygen per minute and finally while standing up (stand up dP20/dt). All subjects underwent extensive cardiac autonomic testing. In this cross-sectional study the recordings of basal values and of the functional parameters after arterial occlusion and during breathing oxygen did not differ significantly between groups A, B and C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219264 TI - No decreased erythrocyte deformability in type 1 (insulin-dependent) diabetes, either by filtration or by ektacytometry. AB - A lower erythrocyte deformability, which causes impairment of the microcirculation, is postulated to contribute to diabetic organ complications. Erythrocyte deformability was measured in four groups of type 1 (insulin dependent) diabetic subjects and 30 controls by filtration and ektacytometry. Twenty-five patients without organ complications, 21 with microalbuminuria, 13 with overt nephropathy and 12 with leg ulceration were studied. No decreased erythrocyte deformability was found in any of the diabetic groups with either technique, and neither did the total group of 71 diabetic subjects have a lower erythrocyte deformability when compared with the controls. In order to imitate local conditions in the kidney, erythrocyte deformability was also measured in hyperosmolar solutions. Again no differences were found between the diabetic groups separately or as a whole and the controls. Furthermore no correlation was found between erythrocyte deformability and the plasma glucose or glycosylated haemoglobin level. PMID- 8219265 TI - The optimization of large-scale density gradient isolation of human islets. AB - The use of the COBE 2991 cell processor (COBE Laboratories, Colorado) for large scale islet purification using discontinuous density gradients has been widely adopted. It minimizes many of the problems such as wall effects, normally encountered during centrifugation, and avoids the vortexing at interfaces that occurs during acceleration and deceleration by allowing the gradient to be formed and the islet-containing interface to be collected while continuing to spin. We have produced cross-sectional profiles of the 2991 bag during spinning which allow the area of interfaces in such step gradients to be calculated. This allows the volumes of the gradient media layers loaded on the machine to be adjusted in order to maximize the area of the gradient interfaces. However, even using the maximal areas possible (144.5 cm2), clogging of tissue at such interfaces limits the volume of digest which can be separated on one gradient to 15 ml. We have shown that a linear continuous density gradient can be produced within the 2991 bag, that allows as much as 40 ml of digest to be successfully purified. Such a system combines the intrinsic advantages of the 2991 with those of continuous density gradients and provides the optimal method for density-dependent islet purification. PMID- 8219267 TI - Health care standards: the interstitial matter of quality programs. PMID- 8219266 TI - The role of protein kinase C in insulin biosynthesis. AB - Activation of protein kinase C (PKC) by the phorbol ester 4 beta-phorbol myristate acetate (4 beta-PMA) stimulated (pro)insulin biosynthesis in collagenase-isolated rat islets of Langerhans, as assessed by measuring the incorporation of [35S]cysteine into proinsulin and insulin after fractionation by high performance liquid chromatography. The stimulatory effects of 4 beta-PMA were observed at a substimulatory concentration of glucose (2 mM) but were not additive to the stimulatory effects of 20 mM glucose on insulin biosynthesis. Prolonged exposure to 4 beta-PMA caused a marked down-regulation of PKC activity in islets. PKC-depleted islets showed a much reduced biosynthetic response to 20 mM glucose, but this was caused, at least in part, by an enhanced basal rate of (pro)insulin synthesis. These elevations in the basal rate of insulin synthesis were not secondary to an increase in the amount of preproinsulin mRNA in PKC depleted islets since Northern blot analysis showed that prolonged exposure to 4 beta-PMA, and the subsequent loss of PKC activity, did not detectably alter basal levels of preproinsulin mRNA. These results suggest that the activation of PKC stimulates (pro)insulin synthesis in rat islets by enhancing translation of existing preproinsulin mRNA, and that this may play some part in the biosynthetic responses of beta-cells to glucose. PMID- 8219268 TI - Solving the quagmire of clinical standards development and implementation. PMID- 8219269 TI - Practice guidelines: a standard whose time has come. PMID- 8219270 TI - Application of the new ANA framework for nursing practice standards and guidelines. PMID- 8219271 TI - Decreasing falls by the application of standards of care, practice, and governance. PMID- 8219272 TI - Critical pathway patient outcomes: the missing standard. PMID- 8219273 TI - Case management: a multidisciplinary approach to the evaluation of cost and quality standards. PMID- 8219274 TI - Navigating the teaching-learning process: education standards for reaching quality improvement destination. PMID- 8219275 TI - Patient self-medication: an innovative approach to medication teaching. PMID- 8219276 TI - Continuous quality improvement (CQI) concepts. PMID- 8219277 TI - The Escherichia coli gcvT gene encoding the T-protein of the glycine cleavage enzyme system. AB - Plasmid pGS146 carries the Escherichia coli gcv system on a 7.12 kb SalI-BamHI DNA insert fragment. The DNA sequence of a gene which presumably encodes the T protein of the glycine cleavage (GCV) enzyme complex was determined. The gene, designated gcvT, encodes a polypeptide of 364 amino acids with a calculated molecular weight of 40,146 daltons. In a minicell system, the SalI-BamHI fragment directs the synthesis of three polypeptides with Mr values of about 93,300, 43,300 and 17,400 daltons. When gcvT was inactivated by insertion of a translation terminator sequence, the Mr 43,300 dalton polypeptide was not observed. The deduced amino acid sequence of the E. coli T-protein was compared with the sequence of the T-protein from bovine liver. 190 of 364 amino acid residues are identical or chemically similar between the two proteins. An S1 nuclease mapping experiment located the transcription start point for gcvT. Single basepair changes were made in the promoter -10 and -35 sequences. These mutations significantly reduced expression from a gcvT-lacZ gene fusion. The gcvT gene is transcribed and translated in the same direction as the gcvH gene. PMID- 8219278 TI - cDNA sequence, gene structure, and cholinesterase-like domains of an esterase from Caenorhabditis elegans mapped to chromosome V. AB - The structure of an esterase gene from Caenorhabditis elegans has been determined by comparison of the sequences in genomic and cDNA clones. The gene was mapped close to the center of chromosome V (1.7 centimorgans to the left of dpy-11) and is therefore distinct from the gut esterase gene ges-1. It possessed 7 short introns. The 5' splice site of intron 3 presented the sequence GC instead of the usual GT that was found in the other six introns. The cDNA was trans-spliced with the short leader SL1. The open reading frame indicated that a protein of 557 aminoacids was encoded. The deduced aminoacid sequence did not present a signal peptide at the N-terminal but a potential N-myristoylation site (GXXXS) provided that the initiator methionine was removed. This protein should therefore remain intracellular. Comparison of this C. elegans sequence to other protein sequences in databases, as well as the analysis of the secondary structure in the protein showed that it belongs to the subgroup of esterases in the alpha/beta hydrolase fold family. PMID- 8219279 TI - Cloning, sequencing and expression of a Pasteurella haemolytica A1 gene encoding a PurK-like protein. AB - A membrane protein antigen of Pasteurella haemolytica A1 encoded on the recombinant plasmid pYFC13 is isolated and characterized. Nucleotide sequence analysis of the insert DNA in pYFC13 identified the gene mpa1, which codes a protein of approximately 45 kDa without signal sequence. The deduced amino acids from the DNA sequence are homologous to Bacillus subtilis PurK by 29.4%; to Schizosaccharomyces pombe Pur6 by 29.34%, to Saccharomyces cerevisiae Pur6 by 25.867%; and to E. coli PurK by 25.223% identity, respectively. The purK and pur6 from these organisms are responsible for the activity of 5'-phosphoribosyl- 5 amino-4-imidazole carboxylase which is involved in de novo purine biosynthesis. The protein was over-expressed in E. coli by its own promoter. The antigen we designated as Mpa1, could be localized to the cytoplasmic membrane of both P. haemolytica A1 and E. coli TB1 harbored pYFC13. The Mpa1 was antigenic in rabbit and in cattle since both animals produced antibody against this protein. PMID- 8219280 TI - The mouse Mel-18 "RING-finger" gene: genomic organization, promoter analysis and chromosomal assignment. AB - The chromosome gene for mouse Mel-18 (mMel-18) protein has been isolated and characterized. The entire mMel-18 gene is composed of thirteen exons spanning about 15 kilobases, in which the protein is encoded by exons 5-13. The "RING finger" motif of Mel-18 protein that displays a significant evolutionary resemblance to other RING-finger nuclear proteins is encoded by exons 5 and 6. Exon 13 encodes a C-terminal proline/serine-rich domain that is homologous to some transactivator proteins. Sequence analysis of the 5'-flanking region revealed the presence of potential binding sites for transcription factors such as SP-1, NF-1, NF-kappa B and c-myc/max. At least two major cap sites and three minor cap sites were identified by S1 mapping and primer extension analysis. We propose that the mMel-18 gene is regulated by two different types of promoters, the CAAT-TATA box promoter and the GC-rich TATA-less promoter. The 2.4 kb DNA fragment of the 5'-flanking region exhibited constitutive promoter activity when transfected into L cells. By the in situ hybridization method, the mMel-18 gene was assigned to mouse chromosome 10C3. PMID- 8219281 TI - Retroviral-like features in the monomer of the major satellite DNA from the South American rodents of the genus Ctenomys. AB - It is well known that uninfected mammalian cells contain DNA sequences which are closely related to retroviral genomic segments. However, these sequences seldom (if ever) have been found associated to highly repetitive (satellite) DNA. RPCS is a 348 bp monomer of a major satellite DNA from the South American rodents of the genus Ctenomys. It was found that RPCS contains several elements which are typical of the U3 region of retroviral LTRs. These elements are: a) a polypurine tract; b) two enhancer core sequences; c) two NF1 binding sites; d) two C/EBP binding sites; e) two CCAAT-motifs; f) a TATA box, and g) two putative polyadenylation motifs. Furthermore, the relative positions of these elements are as in the U3 retroviral regions. PMID- 8219282 TI - The nucleotide sequence of the 5' flanking region of the Arabidopsis ACS2 gene. AB - The ACS2 gene of Arabidopsis thaliana encodes 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (EC 4.1.1.14) - the key regulatory enzyme in the biosynthetic pathway of the plant hormone ethylene. The gene is unique among ACC synthase genes isolated thus far in that it is highly expressed in both reproductive (e.g. flower) and vegetative tissues (e.g. leaves and roots). In addition, the accumulation of ACS2 transcripts is greatly induced by protein synthesis inhibition (Liang et al 1992). We report here the DNA sequence of the 5' flanking region of the ACS2 gene and an analysis of the sequence with respect to the potential cis-acting regulatory elements that can be recognized by DNA-binding proteins from plants and other organisms. PMID- 8219283 TI - The molecular cloning and sequence of the common marmoset interferon-gamma (MaIFN gamma) gene. AB - A DNA fragment covering marmoset interferon gamma (MaIFN-gamma) was cloned from the DNA of peripheral blood leucocytes, sequenced and compared to its human IFN gamma counterpart. The two nucleotide sequences were found to be highly homologous (90.3%). The position of the exons are directly comparable with those of the human IFN-gamma gene and follows the pattern of structural conservation found elsewhere. The present work makes available recombinant MaIFN-gamma for animal experiments. PMID- 8219284 TI - Nucleotide sequence of a cDNA encoding the chicken receptor protein kinase of the TGF-beta receptor family. AB - We have isolated RPK-2 cDNA from chick embryo cDNA library that encodes a receptor protein kinase of the TGF-beta receptor subfamily. The deduced amino acid sequence reveals the presence of a hydrophobic transmembrane helix and a kinase domain distantly related to type II receptor for TGF-beta. The kinase domain sequence is most similar to RPK-1 identified recently in the chick embryo. Several cysteine residues are contained in the amino-terminal ectodomain, suggesting the protein as a receptor for a peptide growth factor of the TGF-beta family. PMID- 8219285 TI - The putative origin of heavy strand replication (oriH) in mitochondrial DNA is highly conserved among the teleost fishes. AB - We have determined the nucleotide sequence of a 645 bp EcoRI-HindIII fragment from mitochondrial DNA of Arctic charr, Salvelinus alpinus. The sequence includes the tRNA(Phe) gene, part of the small subunit ribosomal RNA gene as well as the putative origin of heavy strand replication located at the major non-coding region, the D-loop containing region. Upon comparison of the Arctic charr sequence to mitochondrial DNA sequences from several distantly related teleost fishes, the origin of heavy strand replication was found to be highly conserved among the teleost fishes. PMID- 8219286 TI - [Home health care and nursing for patients in Japan with intractable diseases]. AB - The progress of home health care as practiced in Japan, was analyzed in relation to changes in the society, and the requirements for meeting future needs. The development of home health care consists of three stages: the first stage is a trial stage where home health care is adopted on a trial basis; the second stage incorporates nursing care within the restriction of personal care only; and in the third stage, enhancement and systematization of home health care occurs. To meet the nursing needs of the increasing number of at-home patients requiring medical treatment, the following are necessary: (1) Services should be available twenty-four hours a day all year round. (2) Systematized education should be developed for teaching nursing skills necessary for high technological care. (3) Development and distribution system for home nursing care goods and equipment is necessary. (4) A regular evaluation system for nursing services should be established. (5) Research studies on home health care and nursing should be encouraged. PMID- 8219287 TI - [X-linked mental retardation: variations in the fragile X mutations and genetic counseling]. AB - The fragile X syndrome is one of the most common forms of genetic mental retardation and is caused by elongation of a small target DNA fragment containing a repeat of the trinucleotide CGG located in a 5' exon of the FMR-1 gene on the X chromosome. The genetic mutations were classified as two main types, premutation and full mutation, according to the size of the elongation. Because clinical findings are varied in patients with the fragile X syndrome, diagnosis of the disease is very difficult when based only on clinical symptoms. Molecular findings in three families with the fragile X syndrome showed that individuals with the full mutation were moderately mentally retarded, but individuals with the premutation had normal intelligence. The intellectual quotient levels in the families related to the sizes of the mutation which were unstable from generation to generation. These findings suggested that molecular studies in patients with mental retardation are very usefull to diagnose the fragile X syndrome, and that genetic counseling should be carried out based on the DNA analyses of the FMR-1 gene in the family members. PMID- 8219288 TI - [Long-term hypertension control in a community--comparison of stroke incidence and hypertension control between participants and nonparticipants in health examinations]. AB - Since 1969, community-based hypertension control program has been conducted for non-company-employed residents aged 40 and over (3,039: 70% of the residents) in Noichi town, Kochi prefecture. The program is composed of annual health examinations, health education and referral of hypertensives to local physicians. Incidence and mortality of stroke have declined along with a decrease in systolic blood pressure levels. However, during the period of 1982-84, stroke incidence was higher for nonparticipants in health examinations than in the participants of the same age group. For an understanding of the state of detection and control of hypertension in nonparticipants aged 40-69 of the 1982-84 health examinations, blood pressure was examined for 312 subjects randomly selected from the 2,062 nonparticipants. Blood pressure levels were significantly higher in nonparticipants than in participants. In addition, the proportion of hypertensives who were aware of their blood pressure levels was lower in nonparticipants than in participants. About 87% of residents aged 40-69 reported that they received blood pressure checkups at least once a year. Persons who were involved in manual labor, sales and services received blood pressure checkups less frequently. Among company employees, the proportion of persons who checked their blood pressures annually was progressively lower with decrease in size of companies. The community hypertension control appears to have contributed to a decline of blood pressure levels and stroke incidence. However, detection and control of hypertension was relatively poor in nonparticipants in health examinations, particularly for employees of small companies. PMID- 8219289 TI - [Determinants of patient satisfaction and intention to continue service utilization: analysis of a survey of outpatients at general hospital]. AB - The patient-perceived quality of hospital ambulatory service and its relationship to patient satisfaction and intention to continue utilization of the service were assessed using a questionnaire which was mailed to 1,695 outpatients of a general hospital in Tokyo (response rate, 77.2%). Patient satisfaction and satisfaction and intention of continuing service utilization were each assessed and both for physicians and for the hospital. The quality of hospital outpatient service was evaluated for 36 items, and 9 patient evaluation scales were extracted by factor analysis: i.e., "treatment results", "physician competence and explanation", "physician warmth and commitment", "reputation of hospital and physician", "services by nurses and non-clerical staff", "services by clerical staff", "medical costs and barriers", "hospital environment" and "accessibility to medical care". These scales, with the exception of "accessibility of medical care", had high internal consistency. Accessibility was then decomposed into 4 independent scales-"waiting time", "outpatient clinic hours", "availability of services when needed" and "transportation convenience". The effects of a total of 23 variables, consisting of 12 patient evaluation scales, sex, age, education, income, clinical departments (4 dummy variables), "frequency of service utilization", "perceived severity of disease" and perceived necessity for medical care intervention" on patient satisfaction and patient intention to continue utilization of services were assessed by multiple regression analysis (forced entry method). The results indicated that patient assessment of "treatment results", "physician competence and explanation", "physician warmth and commitment" and "reputation of hospital and physician are important determinants of patients satisfaction and intention to continue using hospital outpatient service. PMID- 8219290 TI - [A survey of goals and the utilization of numerical goals in the health planning of 47 prefectures]. AB - Health plans of 47 prefectural governments based on the Medical Law of 1985, were evaluated regarding four health planning factors: final goal, implementation plan, development of resources, and evaluation planning. Results of the evaluation showed that 8.5% of the 47 prefectures had defined future level of health based on numerical goals. On the other hand, all of the prefectures had developed numerical goals specifying the number of hospital beds in each medical district. A major component of health planning is improvement in the accomplishment of the implementation plan. There were 14 prefectures which had numerical goals for the upgrading of facilities and for manpower development to meet future health care activities. The following factors are required in the health planning to meet the needs for improving the health status of the population. 1) Including in the future health goals, in addition to the number of medical bed in regional areas, objective levels of health that should be attained. 2) Development of practical plans for evaluation of effectiveness of health planning. PMID- 8219291 TI - [Health personnel staffing requirements for health examination for three year old children in municipalities in Japan]. AB - Based on the Maternal and Child Health Law, municipalities offer health education, health counseling, health examination, and home visitation service for three year old children and for their mothers. In order to determine personnel staffing requirements for the health examination of three year old children for municipalities in Japan for 1989, data from a questionnaire survey in 1990 conducted by the Ministry of Health, was analyzed. Questionnaires were sent to all municipalities and there were 3,198 responses for a response rate of 97.9%. Results showed that in 1989, only 7% of the 3,198 municipalities were able to perform health examinations for three year old children independently. However 83% of the cities which had populations 500,000 or more were able to perform the health examinations independently. In both the large cities designated by the Government and those cities which have Health Centers, the health personnel system adequately supported these health examinations. Due to the lack of health personnel, rural towns and villages with small populations required public health nurses to be assisted by other staff, most often public health nurses from prefectural Health Centers. For example, in those areas with populations less than 3,000, 43% of the total volume of the work required to be performed by public health nurses during the health examinations had to be covered by assistance for prefectural public health nurses. PMID- 8219292 TI - [Adequacy of translating health survey questionnaires for cross-cultural surveys- the case of the Todai Health Index]. AB - The adequacy of the language translation of self-administered questionnaire items was examined in a comparative study of adolescent mental health between Japan and the United States. As a screening instrument to be used in both countries, the Todai Health Index (THI) questionnaire had been translated from original Japanese into English. The original version was administered to 570 Japanese adolescents and the translated version was given to 295 middle school students in the United States (aged 12 to 15). The equivalence of the two versions was re-examined based on the results of the surveys by a team of researchers from both countries including a bilingual investigator. For the items which produced a statistically significant different response pattern between the two samples, the investigators attempted to determine whether the observed difference could be attributed to an inadequate translation or to a real cultural difference. For those items judged to suffer from inadequate translation, modifications were made to improve cross cultural equivalence. The above methodological procedure, though not perfect, proved to be relatively simple but very useful in resolving many practical issues in cross-cultural studies and produced interesting findings. For example, the phrase "worry about" was found to not adequately capture the Japanese meaning of "ki-ni-naru" and instead the phrase "concern about" or "care" was suggested as a more appropriate substitute. Very little is known and insufficient attention has been given to the effect of translation in cross-cultural surveys. These investigations suggest the benefit of more extensive studies and focused discussions of reliability of the translated survey instruments by public health researchers involved in international comparisons. PMID- 8219293 TI - [Bacteriuria in hospitalized elderly--its prevalence, significance and management]. PMID- 8219294 TI - Plasticity of binaural hearing and some possible mechanisms following late-onset deprivation. AB - Evidence for binaural plasticity resulting from late-onset deprivation comes from behavioral adaptation in humans following experience of abnormal binaural cues, from physiologic changes in the organization of the cerebral cortex, and from anatomic rewiring of some of the pathways underlying binaural hearing in the brain stem. Some of this evidence is indirect, and the long-term functional consequences of these changes in the nervous system are unclear. Nevertheless, there are now sufficient data available on plasticity in mature nervous systems to warrant a substantially increased research effort in this field. Among the questions to be addressed are the site(s) of reorganization in the auditory system, the effects of different types of deprivation, and the neural mechanisms underlying the plasticity. PMID- 8219295 TI - Monaural hearing aid effect: case presentations. AB - A phenomenon associated with a monaural hearing aid fitting has previously been identified. In some individuals with bilateral sensorineural hearing loss (BSNHL), the speech-recognition score (SRS) of the unfitted ear deteriorates over time. Nine subjects with BSNHL who chose a monaural hearing aid fitting are chronicled from the time of their initial hearing fitting to the time where the SRS of the unfitted ear dropped below the lower limit of the 95 percent critical difference value. All nine of the subjects were fitted with binaural amplification at the time of the significant change in the SRS. Five of the subjects retained the binaural amplification arrangement while three of the subjects returned their second hearing aid after a "30 day trial," and one subject stopped wearing the second hearing aid 8 months after the binaural fitting. All the subjects who chose to utilize the binaural arrangement had their SRS return to within the 95 percent critical difference range as did two of the individuals who chose to retain the monaural arrangement. PMID- 8219296 TI - Role of perceptual acclimatization in the selection of frequency responses for hearing aids. AB - Previous work concerning the late-onset auditory deprivation and/or acclimatization effect in adult hearing-aid users has suggested that the benefits of a particular frequency response from a hearing aid may not become apparent until material exposure to that frequency response has been achieved. The generality of that finding was tested further. A group of subjects who were established users (12 to 15 months) of a particular frequency response (limited at high frequencies by the system of provision) were re-prescribed with a theoretically advantageous frequency response according to the NAL prescription. Using a speech-in-noise test (word identification) and a sentence verification test, the benefits of the re-prescription were not (or at best only marginally) evident upon immediate testing but became statistically significant and of material clinical magnitude following experience with the represcription for 8 and 16 weeks. These results suggest that comparative selection regimes and research designs based upon little or no experience of the listening environment through the hearing aid are likely to seriously misrepresent the benefits available to the hearing-impaired listener. PMID- 8219297 TI - Short-term and long-term effects on the masking level difference following middle ear surgery. AB - The masking-level difference (MLD) was measured in a group of adult listeners having unilateral otosclerosis before stapedectomy surgery, 1 month following surgery, and 1 year following surgery. The results indicated that the MLD in this group improved significantly over each of the sequential tests. In contrast, for a group of normal-hearing listeners, the MLD did not change significantly over sequential testing. The results support an interpretation that a period of exposure to abnormal binaural auditory input (as occurs in a unilateral conductive loss) can blunt sensitivity to binaural cues after normal binaural input has been restored in most adult listeners, however, there appears to be a relatively long-term readjustment or adaptation, such that the sensitivity to binaural cues recovers to a normal or near-normal level at the 1-year postsurgery retest. Two of eight listeners did not show recovery to a normal MLD value over this time period. The efficiency and rate of readjustment may differ among individuals. PMID- 8219298 TI - Apparent auditory deprivation in children: implications of monaural versus binaural amplification. AB - This study investigated the effects of monaural versus binaural amplification upon the speech recognition scores (SRSs) of children with bilateral moderate sensorineural hearing loss after more than 4 years of hearing aid use. There was a significant decrease in SRSs for the unaided ears of the monaural hearing aid users, but there were no significant differences between initial and retest SRSs for their aided ears, or for both ears of those using binaural amplification. The SRS reduction was found to be large enough to be significant on an individual ear basis (by exceeding 95% confidence limits of the binomial model) in five of the ten unaided ears of the monaurally fitted children, but this did not occur for any of the initial-retest SRS differences in the aided ears of either group. These findings demonstrate that the auditory deprivation effect, which has been reported for adults using monaural hearing aids, is also found in children. PMID- 8219299 TI - Ear dominance for nonsense-syllable recognition ability in sensorineural hearing impaired children: monaural versus binaural amplification. AB - The purpose of this investigation was to determine whether an auditory deprivation/dominant-ear effect associated with nonalternating monaural amplification is present in children. Subjects were 35 children with bilateral symmetric, moderately severe to profound, sensorineural hearing impairment. Seventeen were fitted with nonalternating monaural amplification and 18 were fitted with binaural or alternating monaural amplification. Taped speech stimuli consisted of 20 nonsense syllables. The mean age at which subjects were fitted with amplification was 4.8 years for the monaural group and 4.9 years for the binaural group. The mean period between hearing-aid fitting and the initial test was 4.1 years for the monaural group vs. 3.4 years for the binaural group. The mean interval between the age at retest and the age at which the subject was fitted with amplification was 15.8 years for the monaural group and 13.9 years for the binaural group. Results revealed a significant difference in the mean interaural difference score (IDS) for nonsense-syllable recognition (NSR) at the initial test and at the retest between group A and group B. The results also revealed that the progression from initial test to retest in the IDS for NSR was 10.7 percent for the nonalternating monaurally fitted subjects as compared with 3.3 percent for the binaurally or alternating monaurally fitted subjects. Results are discussed in relation to the theories of auditory deprivation and ear dominance. PMID- 8219300 TI - Recovery of speech perception performance after prolonged auditory deprivation: case study. AB - The case reported here, a 26-year-old woman, has a bilaterally symmetric, severe to-profound, sensorineural hearing loss, acquired early in life. Phoneme recognition scores were essentially symmetric at the onset of the investigation. She was basically monaurally aided from age 4 to age 24, at which time a loss of function in the aided ear prompted the change to binaural amplification. When monaurally aided, this subject had consistently given phoneme recognition scores around 80 percent and 40 percent in the aided and unaided ears, respectively, even though the pure-tone thresholds were almost identical. After several months of hearing aid use, phoneme recognition in the previously unaided ear rose to 75 percent. At the time of writing, this subject is able to hold unstructured telephone conversations via this ear. These data suggest that the earlier poor performance of the unaided ear was due, not to an irreversible loss of peripheral function, but to a lack of experience in interpreting the patterns of neural stimulation generated by that ear. PMID- 8219301 TI - Auditory deprivation and recovery in adults with asymmetric sensorineural hearing impairment. AB - The purpose of this investigation was to investigate (1) whether auditory deprivation effects are present in the poorer ears of adults with asymmetric sensorineural hearing impairment and (2) whether, if such effects are present, they can be reversed by amplification. Subjects were 16 males with asymmetric sensorineural hearing impairment, 8 of whom had never been aided, 6 of whom were aided monaurally at the initial test, and 2 of whom were unaided at the initial test but aided monaurally later on. Data were obtained from a retrospective review of records. The initial and retest (2-13 years post initial test) suprathreshold speech-recognition scores for 50-word, taped lists of the CID W-22 PB words were analyzed. The results revealed a significant difference between the initial and retest mean suprathreshold speech-recognition scores for the poorer ears of the unaided subjects. The results also revealed no significant change from the initial test to retest in six of the aided ears and significant improvement from the initial test to retest in the two of the aided ears. The findings are discussed with reference to the theory of auditory deprivation and recovery from auditory deprivation by amplification. PMID- 8219302 TI - Late-onset auditory inactivity (deprivation) in persons with bilateral essentially symmetric and conductive hearing impairment. AB - The purpose of this investigation was to examine the effects of prolonged monaural amplification on the suprathreshold speech-recognition scores in the unaided ears of 46 persons with bilateral essentially symmetric and conductive hearing impairment and aided ears of 46 other persons with bilateral essentially symmetric and conductive hearing impairment. All subjects were less than 50 years of age. The suprathreshold speech-recognition loss scores for taped monosyllabic German PB words were analyzed. The frequency distribution of pure-tone averages was essentially equivalent for the aided and unaided ears. Although the magnitude of hearing impairment was essentially equivalent for the aided and unaided ears, the unaided ears tended to have large suprathreshold speech-recognition loss scores than the aided ears. The results are discussed in relation to theories of auditory deprivation and inactivity from monaural amplification. The clinical significance of these findings in relation to ear surgery is also discussed. PMID- 8219303 TI - The relevance of suffering and identifying with others when allocating resources, and clinical implications of the elasticity of the law. PMID- 8219305 TI - Conflict in medical ethics cases: seeking patterns of resolution. PMID- 8219304 TI - Outcome predictors in the early withdrawal of life support: issues of justice and allocation for the severely brain injured. PMID- 8219306 TI - Phone fees: a justification of physician charges. PMID- 8219307 TI - Requirements for ethics, socioeconomic, and legal education in postgraduate medical programs. PMID- 8219308 TI - Clinical ethics training for staff physicians: designing and evaluating a model program. PMID- 8219309 TI - Confidentiality in the age of AIDS: a case study in clinical ethics. PMID- 8219310 TI - Gathering information and casuistic analysis. PMID- 8219311 TI - The legal dilemma of partner notification during the HIV epidemic. PMID- 8219312 TI - U.S. Catholic bishops on nutrition and hydration: a second opinion. PMID- 8219313 TI - Clinical ethics and reform of access to health care. PMID- 8219314 TI - Justice and outcomes research: the ethical limits. PMID- 8219315 TI - Ethics, outcomes, and epistemology: how should imprecise data figure into health policy formulation? PMID- 8219316 TI - Cutting to the bone in conflict resolution: "getting to yes" with hormonal replacement therapy. PMID- 8219317 TI - Medical ethics cases: moral conflict or confusion? PMID- 8219318 TI - Telephone fees: are they worth it? PMID- 8219319 TI - Medical ethics in medical education: finding and keeping a place at the table. AB - Although almost three decades have passed from the early days of the modern medical ethics movement, both articles discussed here manifest variations of some old concerns. First, an acceptance of ethics is incorporated into general requirements and found in specific programs, but ethics is not given great attention by those who decide who will enter the medical profession. Second, in the clinical setting itself, practitioners are busy and the teaching process is placed amidst a multitude of other concerns. And third, the goals for resident and faculty education are remarkably similar to those proposed for undergraduates (awareness, development of analytical skills, involvement in patient care, and so forth). The evaluation of ethics instruction, which has been a concern since the 1960s, has a new face. Upon entering the medical-education setting, humanists found that there was a need for accountability that they had not generally experienced in their university teaching. Yet, they also knew that ethics was different from other medical courses, and that quantifying its special contribution was difficult. Today's general societal emphasis on cost and outcome as measures of the value of education gives consideration of evaluation a critical role. White and Zaner, and most of the other authors cited here, mention the need for systematic accounting of the results of teaching, as well as the difficulty of evaluation. The evaluation of the effectiveness of ethics instruction will remain problematic, yet it is necessary in the changing health care market. To the degree to which it is possible to communicate knowledge about ethics, residency and other accrediting bodies can provide means to evaluate the results of teaching.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219320 TI - Application of electrospray ionization mass spectrometry with maximum-entropy analysis to allelic 'fingerprinting' of major urinary proteins. AB - Mixtures of a specific group of proteins, the major urinary proteins (MUPs), believed to have a role in odorant binding, have been analysed by electrospray ionization mass spectrometry. The data obtained from conventional transformed electrospray data confirm that the molecular weights of the protein mixtures, deduced from published sequences, lie in the molecular weight range 18,600 to 19,000 Da. Application of maximum-entropy analysis to the raw electrospray data has confirmed a heterogeneity in MUP composition, consistent with allelic similarities (and differences) between the different mouse strains. This work demonstrates the use of maximum entropy in the assessment of protein content and in the subsequent resolution enhancement of naturally occurring protein mixtures containing components of closely similar molecular mass. PMID- 8219321 TI - Mass spectrometric sequencing of linear peptides by product-ion analysis in a reflectron time-of-flight mass spectrometer using matrix-assisted laser desorption ionization. AB - In matrix-assisted laser desorption ionization (MALDI) a large fraction of analyte ions undergo post-source decay (PSD) during flight in the field-free drift path. By means of a modified two-stage reflectron, product ion time-of flight spectra of medium-sized linear peptides (up to 2800 u) were recorded, containing full sequence information. Precision, accuracy and mass resolution of fragment ions were almost as good as obtained in high-energy collisionally activated dissociation (CAD) studies performed in four-sector instruments. Instrumental sensitivity was better by at least one order of magnitude. In reflectron time-of-flight mass spectrometry (RETOFMS) the cleavage pattern of PSD products is different from that obtained by high-energy and low-energy CAD. Activation mechanisms of PSD were found to be largely determined by collisional events (ion/neutral) occurring in the acceleration field during early plume expansion. Future potentials of PSD analysis after MALDI are discussed. PMID- 8219322 TI - Matrix-assisted laser desorption ionization of oligonucleotides with various matrices. AB - Ferulic acid, 3-hydroxypicolinic acid (3-HPA), and 2,5-dihydroxybenzoic acid (2,5 DHB) were used as matrices in MALDI of various oligonucleotides. It was found that 2,5-DHB is an excellent matrix for polydeoxyribothymidylic acid. A poly-T oligonucleotide with a size of 130 bases was successfully detected. 3-HPA was found to be a good matrix for MALDI of homo-oligomeric deoxynucleotides as well as those containing four different bases. Parent ions of pd(A)60, d(T)100, d(G)40, and d(C)40 were observed, and a mixed-base oligonucleotide of 150-mer was also detected. Polymer ions of poly-A as large as 420-mer were measured; however, the efficiency for detecting poly-T with 3-HPA as a matrix was slightly worse than when 2,5-DHB was used. Comparisons of three matrices for various oligonucleotides is also presented. PMID- 8219323 TI - Matrix-assisted laser desorption/ionization Fourier-transform mass spectrometry of oligodeoxyribonucleotides. AB - Conditions for the matrix-assisted laser desorption/ionization (MALDI) of oligodeoxyribonucleotides at 355 nm, developed using a 3-Tesla Fourier-transform ion cyclotron resonance mass spectrometer (FTMS), are reported. Efficient ion trapping and matrix selection are critical to the desorption and detection of oligonucleotides by FTMS. The achievable upper mass limit for the MALDI-FTMS of biomolecules on our 3-Tesla system has been extended from approximately 2 kDa to 6 kDa through the use of pulsed-trapping-plate ion deceleration techniques. By implementing the deceleration techniques, molecular ions for bovine insulin (MW = 5733.5), an oligodeoxythymidylic acid, pd[T]10 (MW = 3060.0), and a mixed-base 12 mer (MW = 3611.5) have been measured. For the analysis of oligonucleotides by FTMS, selection of an appropriate MALDI matrix is essential for the generation of [M-H]- ions. 3-Hydroxypicolinic acid provides a significant improvement over 2,5 dihydroxybenzoic acid for production of deprotonated molecules particularly for mixed-base oligomers. MALDI studies using FTMS have been duplicated using a newly constructed time-of-flight mass spectrometer (TOFMS) and oligonucleotide fragmentation on the TOFMS is reduced relative to that observed by FTMS. This may be a consequence of the longer times (milliseconds) required for FTMS detection. PMID- 8219324 TI - Multiply pulsed collision gas for ion axialization in Fourier-transform ion cyclotron resonance mass spectrometry. AB - We present a new multiply pulsed collision-gas technique for ion axialization for Fourier-transform ion cyclotron resonance (FTICR) high-resolution mass analysis. Ions are axialized in the source trap of a dual-trap FTICR spectrometer by azimuthal quadrupolar irradiation for several tens of seconds at a steady-state pressure maintained by repeated pulses of collision gas (argon), followed by removal of the collision gas and detection at a much lower pressure after transfer to the analyzer trap. Magnitude-mode FTICR mass resolving power, m/delta m approximately 1,770,000, for [M+K]+ ions from laser-desorbed/ionized leucine enkephalin at m/z 594 is demonstrated. This mass resolving power is the highest yet reported for a peptide with any type of laser desorption/ionization mass analyzer. PMID- 8219325 TI - Co-operation in veterinary education between sub-Saharan Africa and the developed countries: experience of the University of Zambia. AB - As is the case with many other veterinary schools in sub-Saharan Africa, the development of the University of Zambia (UNZA) Veterinary School has been supported largely by aid from the developed countries in the form of general expenditure grants, staff training scholarships and technical assistance. The three major pillars of the policies which have governed interactions between UNZA and donors have been bilateralism, "projectisation" (the supplying of aid within the framework of specific projects) and donor management of aid. These have been blended according to the resources endowed by the donors and the negotiating position of UNZA. The authors discuss the effect of the consequent diverse policies on the development of the UNZA school. It is recognised that high dependence on donors by veterinary schools in sub-Saharan Africa will continue in the future. However, the emerging political and economic integration in the sub region and in the developed countries, as well as the trend towards early specialisation in the veterinary profession in the developed countries at a time when countries in sub-Saharan Africa still require generalists, will mean that co operation within a bilateral framework will become less desirable. It is therefore recommended that veterinary schools in sub-Saharan Africa evolve mechanisms for collective aid negotiations and utilisation of aid. Conversely, co operation between donors in multi-donor supported schools will be essential to minimise rigidity in projects, which tends to undermine the cohesion of multi donor funded schools. PMID- 8219326 TI - Economics and planning in the veterinary undergraduate programme: a model for sub Saharan Africa. AB - Veterinarians in sub-Saharan Africa work in resource-deficient environments. Decisions taken by veterinarians in this sub-region, on animal health, animal husbandry and public health issues, are therefore influenced by economic factors including macro-economic considerations related to the current structural adjustment programmes being implemented in the sub-region. In turn, decisions or advice given by veterinarians have socio-economic consequences on clients, on the effectiveness of the delivery systems for veterinary services and on the growth of national economies. For these reasons, economics and planning should be essential components of all modern veterinary undergraduate programmes in sub Saharan Africa, in order to give veterinarians a basis for making decisions and giving advice which is both technically and economically sound. The authors argue that principles of livestock economics, livestock enterprise management, livestock investment analysis and economics of animal health care are necessary elements in economics and planning courses. They propose a division of these elements into discrete course units to allow for flexibility and adaptability to the different curriculum structures of schools in sub-Saharan Africa and, possibly, continuing professional development courses. The resource requirement for teaching the courses, the integration of the units in the undergraduate programme and the problems which are likely to be encountered in developing the courses are discussed. PMID- 8219327 TI - Application of enzyme-linked immunosorbent assay for epidemiological studies of diseases of livestock in the tropics of Mexico. AB - This study was conducted at the Centre for Research, Teaching and Extension in Tropical Livestock (Centro de Investigacion, Ensenanza y Extension en Ganaderia Tropical) of the Faculty of Veterinary Medicine of the National Autonomous University of Mexico. During the latter part of 1986 and throughout 1988 and 1989, the herd of Holstein x zebu cattle at the University was tested for IgG antibodies to twenty-one viral, bacterial, rickettsial and parasitic agents. Antigens prepared from twenty infectious disease agents were used as the solid phase in an enzyme-linked immunosorbent assay, and the agar gel immunodiffusion procedure was used to test for antibodies against bovine leukaemia virus. The prevalence of IgG antibodies was high (> 50%) for bluetongue virus, Anaplasma marginale and Mycoplasma bovis. Antibodies to Brucella abortus were absent and antibodies against bovine virus diarrhoea virus and infectious bovine rhinotracheitis virus showed a very low prevalence (< 5%). Antibodies to fifteen other antigens showed intermediate prevalence (15-46%). Antibodies to Campylobacter fetus, A. marginale, bluetongue virus, bovine leukaemia virus and Haemophilus somnus displayed seasonal variations. Levels of antibody to bovine leukaemia virus, M. bovis and Listeria monocytogenes exhibited increasing secular trends while antibodies to bovine virus diarrhoea virus and C. fetus showed declining trends. Prevalence of antibodies increased with the age of animals tested. No consistent difference in antibody prevalence was found between three genotypic groups examined. PMID- 8219328 TI - Temperature and the persistence of viruses in Culicoides spp. during adverse conditions. AB - The average daily maximum temperature for the coldest month during the winters of 1977-1978 and 1978-1979, when bluetongue (BT) virus overwintered in a cycle between Culicoides spp. and cattle in western Turkey (Aydin and Izmir provinces), was found to be 12.5 degrees C. This temperature agreed with the lowest temperatures found for Culicoides activity and for flight over long distances. Overwintering of BT virus in western Turkey and Lesbos (1979-1980), African horse sickness (AHS) virus in Spain (1987-1990) and BT and epizootic haemorrhagic disease of deer (EHD) viruses in British Columbia (1987-1988) was assessed using the following conditions for survival: maximum temperatures > or = 13 degrees C on 45% of days or more, a weighted "degree day" value of > or = 1.35 of 6 and an average daily maximum temperature of > or = 12.5 degrees C (all for the coldest month) together with a total of 40 days or fewer with maximum temperatures < 13 degrees C and < or = 10 consecutive days with maximum temperatures < 13 degrees C. Using these criteria, overwintering is unlikely to have occurred in Culicoides in Lesbos, Madrid, Toledo, Ciudad Real or British Columbia, but could have taken place in western Turkey (Aydin and Izmir) and southern Spain (Guadalquivir, Guadiana and Tagus Valleys). Isotherms of average daily maximum temperatures of 12.5 degrees C and 18 degrees C for the coldest month were drawn on maps covering various regions of the world, to indicate areas where virus and Culicoides activity could continue during the winter and to compare these areas with the known distribution of BT, EHD, AHS and Akabane infection. PMID- 8219329 TI - Health surveillance of the transfer of bovine embryos fertilised in vitro. AB - The production of embryos fertilised in vitro is part of the third generation of biotechnologies applied to reproduction and is now undergoing development and application in the field. International exchanges of these embryos have already commenced. However, there are certain associated health risks. In decreasing order of importance, these involve dangers inherent in the initial biological material from which gametes and various somatic cells vital to such production (follicular and tubal cells, etc.) are derived, then possible external contamination during the production process, and finally storage and transport. Although the research which has been conducted on the interaction between these embryos and pathogens is still rather limited, as the technique has been under development for only a short time, it is clear that the media in which the oocytes undergo maturation, the spermatozoa undergo capacitation or the embryos are cultured constitute excellent indicators of the potential microbiological or viral environment. This can be utilised in health surveillance of the manipulations. Recently, specific recommendations for making such exchanges safe have been inserted into the Office International des Epizooties International Animal Health Code. These recommendations are based on the concept of official approval of specific embryo transfer teams and examination of animals from which gametes are obtained. PMID- 8219330 TI - Epizootiology of foot and mouth disease in Saudi Arabia: I. Analysis of data obtained through district field veterinarians. AB - Data on the epizootiological status of foot and mouth disease (FMD) in all districts of Saudi Arabia were obtained through responses to a specifically designed questionnaire from field veterinarians working in different Directorates of Agriculture throughout the country. Suspected clinical occurrence of the disease was reported in seventeen of the twenty-three Directorates. The animal species affected were mainly cattle (in fifteen Directorates) and sheep (in eight Directorates). The disease was suspected among goats and camels in only two Directorates. Some animal owners were unwilling to notify suspicion of the disease. Laboratory diagnosis was not performed in all cases. Vaccination using an appropriately-formulated quadrivalent vaccine incorporating FMD virus serotypes O, A, C and Asia 1 was mainly applied to dairy animals. Limited numbers of locally-bred cattle and sheep were vaccinated in eight and four Directorates, respectively. The data obtained and the recommendations of field staff for improving control of FMD at the national level in Saudi Arabia are discussed. PMID- 8219331 TI - Epizootiology of foot and mouth disease in Saudi Arabia: II. Current status on dairy farms and control measures in operation. AB - Specifically-designed questionnaires were distributed to the managers and/or veterinarians of all dairy farms in Saudi Arabia in order to obtain data on the occurrence of foot and mouth disease (FMD) on these farms from 1971 to 1989, as well as data on current control measures. Of 39 farms, 27 responded to the questionnaire and 15 (56%) reported FMD outbreaks. Notification and collection of samples for diagnosis were not performed consistently. Laboratory tests were undertaken at the World Reference Laboratory for Foot and Mouth Disease, Pirbright, United Kingdom. FMD virus serotypes O, A and C were isolated. Epizootiological factors contributing to the occurrence of FMD in Saudi dairy farms and recommendations for improving control of the disease are discussed in depth. PMID- 8219332 TI - Studies on foot and mouth disease in the eastern region of Abu Dhabi, United Arab Emirates. AB - The present paper describes the status of foot and mouth disease (FMD) in the eastern region of Abu Dhabi, United Arab Emirates, over a three-year period from 1987 to 1989. The disease was prevalent among the various livestock populations in the study area. Type O appeared to be most prevalent followed by types A and Asia 1 which were recorded at lower incidences. Type C was not recorded during the period of study. Two isolates of each serotype were tested for antigenic relatedness to each other and to a reference virus. Both type O isolates were closely related but less related to the reference virus O1 BFS (1860). The type A isolates and the reference virus A22 IRQ 24/64 showed a similar degree of close interrelatedness. In contrast, the two Asia 1 field isolates, while being closely related, showed no antigenic relationship with the reference virus Asia 1 PAK 1/54. The possible implications of these results regarding the current situation of FMD control in the United Arab Emirates and neighbouring countries are discussed. PMID- 8219333 TI - Field and laboratory analysis of an outbreak of foot and mouth disease in Bulgaria in 1991. AB - In July 1991, an outbreak of foot and mouth disease (FMD) occurred near Stefan Karadjovo village in Boliarovo (south-east Bulgaria, close to the Turkish border). The virus isolated was identified in Bulgaria as serotype O and this was subsequently confirmed by the World Reference Laboratory for Foot and Mouth Disease in Pirbright (United Kingdom). Serological studies using bovine sera and monoclonal antibody analysis were made. In addition, the sequence of approximately 170 nucleotides at the 3' end of the 1D gene was determined for the field isolate and for vaccine strains used in Bulgaria. These were compared with other sequences of type O FMD viruses from outbreaks in the Middle East. Serum samples were taken from domestic animals in the region close to the outbreak and examined for anti-FMD virus antibodies to assess the extent (if any) of spread of the virus before or after the outbreak. No evidence of infection was found in these animals. The virus involved in the Bulgarian outbreak was antigenically similar to the O1 vaccine strains but probably did not originate from these strains. The virus was closely related genetically to a group of viruses isolated in the Middle East since 1987, suggesting that it may have been introduced into Bulgaria from an area in the Middle East by unidentified means. PMID- 8219334 TI - Comparison of virus neutralisation and enzyme-linked immunosorbent assay for the identification of antibodies against vesicular stomatitis (Indiana 3) virus. AB - Bovine, equine and swine sera from areas free from vesicular stomatitis virus (VSV) Indiana 3 (IND3)--namely Argentina, Chile, Italy and Uruguay--and endemic areas (in Brazil) were examined for anti-VSV IND3 virus antibodies in order to compare results obtained using the virus neutralisation (VN) test and liquid phase blocking enzyme-linked immunosorbent assay (ELISA). Statistical analysis of the data showed close agreement between the two techniques (K = 0.92). The ELISA gave a higher specificity, positive predictive value and efficiency than the VN test. The ELISA offers the additional advantage of using a non-infectious antigen and can therefore be used for antibody quantification in diagnostic laboratories in VSV-free areas to support epidemiological surveillance programmes. PMID- 8219335 TI - Rinderpest and peste des petits ruminants-like disease in the Al-Ain region of the United Arab Emirates. AB - The author demonstrates that rinderpest prevailed among the cattle population in the Al-Ain region of the United Arab Emirates from 1987 to 1989. A total of twenty-four outbreaks of rinderpest were recorded during the study period. Similarly, evidence of the peste des petits ruminants (PPR) or a PPR-like disease was regularly encountered in small ruminants in a total of forty-one outbreaks. PMID- 8219336 TI - Use of the polymerase chain reaction in differentiating rinderpest field virus and vaccine virus in the same animals. AB - In 1991, a disease with clinical signs indicative of rinderpest was reported in yaks in the former Soviet Union, near the border with Mongolia. At the peak of the epizootic, mortality among affected yaks was 32-42% in adults and 65% in animals less than one year old. Pathological samples were examined independently at two institutes in Russia. Both institutes confirmed the presence of rinderpest using complement fixation, agar gel diffusion and immunoassays. Since vaccination had been initiated to control an outbreak of a similar disease several months earlier, the later cases were possibly due to the vaccine and field rinderpest may not have been present. However, the disease had occurred in non-vaccinated animals and these were then vaccinated against the disease. Tissue samples obtained from these animals, which were examined at the Pirbright Laboratory using gel diffusion assays and specific nucleic acid probes, were found to be positive for rinderpest antigen and nucleic acid. Ribonucleic acid derived from the post-mortem tissue samples was amplified using the polymerase chain reaction and rinderpest-specific primers. Sequence analysis of the amplified deoxyribonculeic acid from the samples revealed the presence of two distinct virus strains, one identical to the Plowright rinderpest tissue culture vaccine and the other related to field strains of rinderpest virus circulating in Asia and the Middle East. PMID- 8219337 TI - Isolation and identification of African horse sickness virus during an outbreak in Lagos, Nigeria. AB - An outbreak of African horse sickness involving two horse stables in Lagos, Nigeria, was investigated. Inoculation of blood from infected horses into suckling albino mice resulted in isolation of a virus which was identified as African horse sickness virus by the complement fixation test. The clinical, pathological and epizootiological findings (reported elsewhere) were consistent with African horse sickness. Potential threats of the epidemic to international horse trade are briefly highlighted. PMID- 8219338 TI - Application of a blocking enzyme-linked immunosorbent assay for serological monitoring of hog cholera (classical swine fever) in Poland. AB - Between 1990 and 1992, serum samples from 55,478 domestic swine were tested by enzyme-linked immunosorbent assay (ELISA) for the presence of hog cholera virus (HCV) antibodies. The amount of antibody in the sera was expressed as the mean percentage inhibition (PI). For diagnosis, the tested sera were diluted 1:2 and considered positive if the PI was less than 25%. Sera giving PI values in the range of 25-50% were retested against HCV and bovine virus diarrhoea virus (BVDV), by neutralising peroxidase-linked assay. Comparison of the serum titres obtained was used for serological diagnosis of hog cholera; the tested sera were considered negative for hog cholera if the titre for BVDV was higher than that obtained for HCV. All sera with a PI higher than 50% were considered negative for HCV and BVDV. All sera were found to be free of antibodies to HCV. BVDV antibodies were demonstrated in 0.40% of the sera tested in 1990, in 1.80% in 1991 and 1.06% in 1992. PMID- 8219339 TI - A natural outbreak of Newcastle disease in guinea-fowl (Numida meleagris galeata) in Nigeria. AB - A natural outbreak of Newcastle disease (ND) was reported in a flock of guinea fowl in Nigeria, affecting 1,029 birds of which 250 (24.3%) died. Paralysis of the legs and wings, coughing, sneezing, white diarrhoea and complete cessation of egg production were observed. Serum samples collected at the onset and during the course of the disease had high ND antibody titres. ND virus was isolated from a pool of brain tissues from diseased guinea-fowl. The ND virus isolate was characterised as a velogenic strain. PMID- 8219340 TI - [Reaction of the complement fixation test on microtitration plates: application to the serology of myxomatosis. Comparative study of the results with the reaction of indirect immunofluorescence]. AB - The authors describe a complement fixation technique on microtitration plates, using an antigen prepared from myxomas induced in rabbits. Compared with indirect immunofluorescence this technique was less cumbersome, more economical, easier to read and (as a conventional procedure) applicable in all laboratories. Results obtained with 165 serum samples tested by both methods showed good correlation and a specificity at least equal to that of indirect immunofluorescence. Taking into account its lower sensitivity, the positive threshold value for complement fixation under the described experimental conditions was a dilution of 1:4 (H50). PMID- 8219341 TI - Successful therapeutic regimens for treating Brucella melitensis and Brucella abortus infections in cows. AB - Three therapeutic regimens were evaluated in 121 cows naturally infected with Brucella melitensis or Brucella abortus, using a combination of long-acting oxytetracycline (LA-OTC), streptomycin (ST) and OTC-intramammary infusion (IMI). Cessation of shedding of Brucella in udder secretions and absence of Brucella in selected tissues were considered criteria for successful treatment. Regimen A (tested on 35 cows) consisted of LA-OTC 25 mg/kg administered intramuscularly (i.m.) every 3 days for 42 days, ST 25 mg/kg i.m. daily for 8 days, and OTC-IMI 20 ml/teat daily for 4 days. Regimen B (tested on 53 cows) was similar to regimen A, except that ST was administered every 2 days for 16 days and OTC-IMI every 2 days for 8 days. Both regimens were equally effective in eliminating Brucella organisms from all cows involved in the tests and no relapses were recorded. However, regimen C, which was similar to regimen A, except that ST was administered every 3 days for 24 days and OTC-IMI every 3 days for 12 days, resulted in the elimination of Brucella organisms from only 30 (91%) of 33 cows. Before commencement of the therapeutic regimens, B. melitensis biovar 1 or 2 had been repeatedly isolated from udder secretions of 103 cows and B. abortus biovar 1 from mammary secretions of 18 cows. PMID- 8219342 TI - A dot immunobinding assay in comparison with the gel diffusion test for the detection of equine herpesvirus-1 antigen from field samples. AB - The authors describe a rapid and simple dot immunobinding assay (DIA) for detection and identification of equine herpesvirus-1 antigen in field samples from cases of abortion, stillbirth, perinatal foal mortality and paralysis. The assay employs a nitrocellulose membrane to which antigen is adsorbed as a dot. Antigen is identified as a coloured dot using a procedure based on the principle of enzyme-linked immunosorbent assay (ELISA). In all, 61 samples were tested by DIA and the test was compared with conventional agar gel immunodiffusion (AGID). With DIA, 44 (72%) samples gave positive results, while only 22 of 61 (36%) samples tested positive by AGID. DIA was observed to be rapid, more sensitive and more specific than AGID, in addition to the obvious advantage of being reagent conservative, inexpensive and simple to perform. PMID- 8219343 TI - Clinical evolution and diagnosis of an outbreak of European brown hare syndrome in hares reared in captivity. AB - The authors studied an outbreak of an acute form of European brown hare syndrome (EBHS) in captive hares. The farm involved had shown negative results in a previous serological test for EBHS conducted on approximately 8% of the animals. Hares which succumbed during the outbreak were submitted to an anatomo pathological examination and the livers of these animals were collected for laboratory analysis. Examination by immunoelectron microscopy and enzyme-linked immunosorbent assay confirmed the diagnosis of EBHS virus (EBHSV). An initial serological survey conducted on the survivors twenty-two days after the outbreak demonstrated an immunological response against EBHSV. During the outbreak, data were collected on morbidity, mortality, incidence of the disease in various age groups, and also on the antigenic characteristics of the virus responsible for the outbreak. PMID- 8219344 TI - Immune response in cattle induced by inactivated rabies vaccine adjuvanted with aluminium hydroxide either alone or in combination with avridine. AB - In a comparative study of two commercial baby hamster kidney rabies vaccines produced in Brazil, the authors were able to demonstrate the following: a) both vaccines provoked a high level of antibody response and protection against challenge in cattle b) in primary vaccination, at least, the addition of avridine (a synthetic lipoidal amine) enhances the immune response in terms of the level and persistence of antibody c) over 90% of cattle vaccinated with either vaccine were protected against experimental challenge one year after revaccination, and the antibody response profile indicated that these vaccines were capable of maintaining antibody titres above protective levels for more than two years after revaccination. On the basis of these results, the authors recommend optional revaccination of young animals (i.e. "primo-vaccinates") at six months of age. Thereafter, annual revaccination should be sufficient to ensure high levels of antibody between vaccination cycles. PMID- 8219345 TI - Epidemiological aspects of outbreaks of food-borne salmonellosis in Scotland between 1980 and 1989. AB - Between 1980 and 1989, 2,212 outbreaks of food-borne infection were reported in Scotland. Of 2,073 episodes for which a causative agent was established, 1,732 (84%) were caused by salmonellae. An average of 980 people were affected each year, while the average number of individuals infected per general outbreak was 16.8. The infected foods were consumed outside Scotland in 25% of the outbreaks. In 75% of 1,107 episodes where the location was specified, the implicated foods were consumed in the home; hotels and restaurants accounted for 15%. Specific food items were identified in 603 (35%) of the 1,732 outbreaks; poultry meat was responsible for 332 (55%) and milk 49 (8%), while eggs accounted for 23 (4%) outbreaks. PMID- 8219346 TI - A European comparative study of serological methods for the diagnosis of infectious bovine rhinotracheitis. AB - A comparison is made of serological diagnostic procedures used for infectious bovine rhinotracheitis in the European Community. A panel of 65 sera, including positive, doubtful, negative and diluted samples was dispatched to nine different European laboratories and tested by neutralisation, enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence and passive haemagglutination, according to the methods used in each laboratory. The results showed good agreement between the various tests for positive and negative sera. However, considerable variability between tests was noted in the "doubtful" category of sera. The highest test sensitivity, as judged by the detection limit for samples serially diluted in negative serum, was found with the blocking ELISAs. A need was identified for international standard reference sera to be made available. PMID- 8219347 TI - Proteoglycans and the modulation of cell adhesion by steric exclusion. AB - The hypothesis that cell aggregation may be driven by linear polymers in the matrix, particularly glycosaminoglycans, is revisited in light of more recent evidence. A model is proposed that extends the concept of steric exclusion to include a role in determining the directionality of cell migration and neurite extension. Recent literature is reviewed to support the conclusion that in living tissues the theoretical conditions for driving aggregation and migration by steric exclusion are met. The ability of a linear polymer to exclude cells is a function of its viscosity, which is optimum with glycosaminoglycans similar to chondroitin sulfate. It is ineffective with low viscosity glycosaminoglycans such as most heparin or heparan sulfate. Hyaluronic acid, a massive polymer, excludes cells poorly when present as an open matrix gel but forms an effective exclusion barrier when attached to the cell surface. According to a model for steric exclusion in organogenesis, when cells have a glycocalyx of linear polymer, they should disperse and migrate down a viscosity gradient of excluding matrix polymer; when they shed or internalize their surface coat in the continued presence of matrix, they should be excluded into a smaller volume and thus stimulated to aggregate. PMID- 8219348 TI - 5A11 antigen is a cell recognition molecule which is involved in neuronal-glial interactions in avian neural retina. AB - In continuing efforts to identify cell-surface molecules involved in cell-cell interactions in the developing avian retina, we identified a monoclonal antibody, the 5A11 antibody, which possessed the ability to interfere with contact dependent glial cell maturation in vitro. We sought to determine the molecular and biochemical identity of the glycoprotein recognized by this antibody, and using additional criteria, establish whether the 5A11 antigen is indeed a cell recognition molecule in the developing retina. Immunohistochemical analyses demonstrate that in the hatchling chick retina and in live cultures of embryonic retina cells, the 5A11 antigen is predominantly associated with Muller glial cells whereas little is observed on neuronal elements. Microsequencing of the major component isolated by immunoaffinity chromatography identifies the HT7 antigen (Seulberger et al.: EMBO Journal 9:2151-2158, 1990), a unique member of the immunoglobulin super gene family (IGSF), as a homologous if not identical protein to the 5A11 antigen. The HT7 antibody, furthermore, recognizes affinity purified 5A11 antigen, and both the HT7 antibody and additional probes generated against the 5A11 antigen recognize a major polypeptide of 45.5 kDa and a minor band of 69 kDa on Western blots of membrane preparations from neural retina. To verify that the 5A11 antigen mediates cell-cell recognition events in the developing neural retina, we examined the consequences of adding antibody to monolayer cultures of dissociated embryonic retina cells and to dissociated retina cells in rotation-mediated suspension culture. Addition of the 5A11 antibody to monolayer cultures results in alteration in the development of the stereotypic arrangement of neurons and glia characterized by a reduction in the number and complexity of neural extensions upon the glial-derived flat cells. Similarly, addition of antibodies generated against the 5A11 antigen to dissociated cells in rotation cultures significantly reduces retina cell reaggregation as monitored by computer-assisted image analysis of cell aggregate size. These data and the identification of the 5A11 antigen as a member of the IGSF establish a role for the 5A11 antigen as a novel recognition molecule in the developing neural retina. PMID- 8219349 TI - Retina cognin, cell signaling, and neuronal differentiation in the developing retina. PMID- 8219350 TI - Puzzle of crystallin diversity in eye lenses. AB - Crystallins have evolved by various mechanisms that are associated with high expression of their genes in the eye lens. The diversity and pattern of crystallins among different species indicate that independent events have occurred at the molecular level during the evolution of the lens in different invertebrates (jellyfish, squid, and octopus) and vertebrates. Although it is possible that different crystallins are needed to fulfill the specific needs of individual species, the unexpectedly large array of proteins that function as crystallins and their abundance in the lens raise the possibility that selective pressures optimizing the function of certain transcription factors in the lens contribute to the recruitment of crystallins. PMID- 8219351 TI - How are non-lenticular cells ready for transdifferentiation? PMID- 8219352 TI - Dynamics of actin and assembly of connectin (titin) during myofibrillogenesis in embryonic chick cardiac muscle cells in vitro. AB - Immunogold electron microscopy of cardiac myocytes microinjected with biotin labeled actin showed that gold labeling was first found around the A band level of myofibrils at their proximal parts. This observation suggests that polymerization of actin and/or the addition of newly formed actin filaments occurs preferentially in association with myosin filaments to increase the myofibrillar girth. At the distal portions of developing myofibrils, their terminal ends were initially labeled, suggesting that continued reorganization and/or de novo formation of myofibrils occurs at these locations. Soon, gold particles were seen along the termini of growing myofibrils. This appears to indicate that actin subunits are added at the membrane-associated ends of preexisting actin filaments to increase the length of myofibrils. Adhesion plaque proteins, e.g., vinculin, do not appear to play any role in assembling actin monomers at these sites on the inner surface of the sarcolemma. Immunofluorescence and immunoelectron microscopy of cardiomyocytes double-stained with antibodies against two distant domains of connectin (titin) filaments and other sarcomeric proteins showed that these domains of connectin filaments and myosin were synthesized almost simultaneously on large polyribosomes and/or associated immediately after the synthesis of these molecules. Connectin and myosin bands were formed after alpha-actinin striations (Z bands) were seen on preformed I-Z-I-like structures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219353 TI - Perlecan gene expression precedes laminin gene expression during differentiation of F9 embryonal carcinoma cells. AB - F9 embryonal cells can be induced to differentiate and synthesize basement membrane proteins. Perlecan and laminin are two basement membrane constituents that have extensive regions of homology. Expression of perlecan and laminin B1 genes was followed during differentiation of F9 cells by measurements of transcription rate and mRNA abundance using nuclear run on assays and Northern hybridizations, respectively. The rate of precursor protein synthesis was determined by immunoprecipitation from lysates of pulse-labeled F9 cells. The results showed that perlecan gene expression responds more rapidly after induction than does laminin B1 gene expression but is ultimately expressed at a substantially lower level than laminin. Thus, the perlecan and laminin genes appear to be regulated by different mechanisms and their gene products are not made in stoichiometric amounts. PMID- 8219354 TI - Accumulation of mRNAs encoding synaptic vesicle-specific proteins precedes neurite extension during early neuronal development. AB - Synaptic vesicles are essential for neuronal synaptic function. We have analyzed the temporal and spatial pattern of mRNA accumulation of two integral membrane proteins specific for synaptic vesicles (synaptophysin and SV2) and a small GTP binding protein associated with the vesicles (rab3a), using in situ hybridization to mouse embryonic tissue sections. Our results indicate that transcription of these mRNAs is not synchronous in the embryo. Detectable levels of synaptophysin and rab3a mRNAs appear during early neurulation (embryonic day [ED] 9.5) both in the CNS and PNS, whereas SV2 mRNA is not observed before ED 10.5. We have also compared the accumulation of these synaptic vesicle protein transcripts during neuroblast proliferation and neuronal differentiation in vitro, using as a model system the embryonic carcinoma cell line P19 which can be induced to differentiate into neurons and glial cells. We observe that transcripts for all three proteins appear in neurons virtually simultaneously soon after withdrawal from the cell cycle. These data suggest that the program of differentiation in vitro is similar to that observed in vivo, but markedly accelerated. In both embryos and P19 cells, transcripts for these three proteins are detectable at a time when most of the neurons have withdrawn from the cell cycle, but prior to neurite extension and synapse formation. PMID- 8219355 TI - Evidence of early topographic organization in the embryonic olivocerebellar projection: a model system for the study of pattern formation processes in the central nervous system. AB - Many projection systems within the peripheral and central nervous system are topographically organized, and it has become increasingly clear that interactions which occur during development determine the projection patterns these systems exhibit in the adult. The olivocerebellar system was chosen as a model system for this study of afferent pattern formation because it has several characteristics which lend themselves to a study of this type. Applications of horseradish peroxidase were made to both the cerebellar primordium and to the inferior olive of embryonic and neonatal mice using an in vitro perfusion system to support the tissue during the transport period. Fibers labeled after restricted olivary applications are limited to particular mediolateral regions of the cerebellum. Similarly, olivary cells retrogradely labeled after discrete cerebellar applications are restricted to particular olivary subdivisions. The results indicate that the olivocerebellar projection displays elements of topographic organization as early as E15 and that the pattern displayed is roughly comparable to that of the adult mammal. The observed trajectories of olivocerebellar fibers and their concomitant association with both Purkinje and cerebellar nuclear cells during embryonic development suggests a role for either or both cell types in the pattern formation process. PMID- 8219356 TI - Development of the vasculature of the anterior pituitary: ontogeny of basic fibroblast growth factor. AB - This study correlates the ontogeny of basic fibroblast growth factor (FGF) with the development of the vasculature of the anterior pituitary (AP) in two strains of rat, Sprague-Dawley (SD) and Fischer 344 (F344). Immunolocalization of FGF was followed from the first appearance of Rathke's pouch (RP) in 12-day (12d) fetuses, through each day of fetal development, and in 5, 20, and 50d postnatal female rats. In addition, the ontogeny of folliculo-stellate cells (FSC) is described, since previous studies suggested that these unique cells might function as phagocytes in the regulation of FGF. In both rat strains, vascularization of the AP commenced in 16d fetuses. In 15-20d fetuses, dense foci of immunopositivity for extracellular FGF were apparent at sites of capillary penetration adjacent to partially disrupted, immature gonadotropes. Localization of FGF was first detected in immature gonadotropes in 18d fetuses and persisted in the cytosol of a subpopulation of gonadotropes thereafter. In 15d fetuses, FGF was localized within the cytosol intimately associated with the peripheral-facing plasma membranes of all cells of the adenohypophysis, and persisted to variable degrees in later fetal stages. Localization of FGF within nuclei of AP parenchymal cells was evident only in 16-17d fetuses. Although the ontogeny of FGF and vascularization of the AP was very similar in both rat strains, the ontogeny of FSC differed markedly. In both strains, follicular lumens contained FGF during late fetal and early postnatal development. However, both electron microscopy and immunostaining for S-100 marker protein revealed that the postero lateral edges of the AP of F344 rats often lacked FSC when compared to SD rats, a situation which could compromise regulation of FGF by FSC at the AP periphery in that strain, and thereby contribute to the neovascularization from systemic blood vessels known to occur in that strain during prolactinoma formation. PMID- 8219357 TI - Distribution of CD9 in the developing and mature rat nervous system. AB - CD9 is a cell surface protein implicated in intercellular signaling that has been identified in selected cell types of the hematopoietic system. To begin a study of the role of CD9 in the developing and adult nervous system, we used the anti rat CD9 monoclonal antibody ROCA2 to determine the distribution of this protein. The identity of the antigen in these tissues was confirmed by immunoblotting and peptide sequencing. Early embryonic sympathetic and dorsal root ganglion sensory neurons and adrenal chromaffin cells all express CD9. ROCA2 also labels the somas, axons, and growth cones of cultured sympathetic and sensory neurons. In the central nervous system (CNS), CD9 is transiently and specifically expressed in embryonic spinal motoneurons. In the adult, central and peripheral glia intensely express CD9. Thus, CD9 is developmentally regulated in a variety of peripheral and central neurons and glia, including proliferating progenitors as well as mature cells. These findings suggest that CD9 may have diverse roles in the nervous system. PMID- 8219358 TI - Evaluation of the chick wing territory as an equipotential self-differentiating system. AB - Harrison (1918: J. Exp. Zool. 25: 413-461) described a developmental field as an "equipotential self-differentiating system." The present study was undertaken to address the question: To what extent can be pre-limb territory of a chick embryo be considered a developmental field? To what extent is the chick pre-limb territory an equipotential self-differentiating system? Two sets of experiments were undertaken to address these questions: (1) Whole and half limb territories were explanted to the celoma of host embryos, and (2) portions of the wing territories were extirpated. The wing exhibited the quality of self differentiation after stage 12, in that the isolated wing territory, grafted to a host celom, could form limbs beginning at stage 12 (however, complete wings formed only from wing territories of stage 16 and older). On the other hand, the chick wing territory did not appear to exhibit equipotentiality. No posterior half limb graft formed normal limbs, and only in two exceptional cases did anterior half limb grafts form limbs. If part or all of the wing territory was removed from chick embryos, normal limbs formed in less than 15% of the cases after stage 15, in about 30% of the cases at stages 13 and 14, but in over half the cases at stages 10-12. Wound healing and reinitiation of limb potential may be responsible for the higher incidence of limb formation at the younger ages. PMID- 8219359 TI - Failure to make normal alpha ryanodine receptor is an early event associated with the crooked neck dwarf (cn) mutation in chicken. AB - We have investigated the molecular basis of the Crooked Neck Dwarf (cn) mutation in embryonic chickens. Using biochemical and pharmacological techniques we are unable to detect normal alpha ryanodine receptor (RyR) protein in intact cn/cn skeletal muscle. Extremely low levels of alpha RyR immunoreactivity can be observed in mutant muscles, but the distribution of this staining differs from that in normal muscle and colocalizes with the rough endoplasmic reticulum immunoglobulin binding protein, BiP. This suggests the existence of an abnormal alpha RyR protein in mutant muscle. In day E12 cn/cn muscle the levels of RyR mRNA are reduced by approximately 80%, while the levels of other muscle proteins, including the alpha 1 subunit of the dihydropyridine receptor, the SR Ca(2+) ATPase, calsequestrin, and glyceraldehyde-3-phosphate dehydrogenase, and their associated mRNAs are essentially normal in cn/cn muscle. There is also a failure to express alpha RyR in cn/cn cerebellar Purkinje neurons. Expression of the beta RyR, a second RyR isoform, is not initiated in normal skeletal muscle until day E18. In cn/cn skeletal muscle significant muscle degeneration has occurred by this time and the beta RyR is found at low levels in only a subset of fibers suggesting the reduced levels of this isoform are a secondary consequence of the mutation. The cardiac RyR isoform is found in cn/cn cardiac muscle, which contracts in a vigorous manner. In summary, a failure to make normal alpha RyR receptor appears to be an event closely associated with the cn mutation and one which may be largely responsible for development of the cn/cn phenotype in embryonic skeletal muscle. PMID- 8219360 TI - Crooked neck dwarf (cn) mutant chicken skeletal muscle cells in low density primary cultures fail to express normal alpha ryanodine receptor and exhibit a partial mutant phenotype. AB - The Crooked Neck Dwarf (cn) mutation in chickens causes marked changes in intact embryonic skeletal muscle. We have investigated whether the cn/cn phenotype develops in vitro, and if cultured muscle cells are suitable for studies of this mutation. The properties of cn/cn muscle cells maintained in low density primary cultures (6.25 x 10(3) cells/cm2) are described in this report. In normal muscle cells, the alpha ryanodine receptor (RyR) isoform appears prior to, and at greater levels than, the beta RyR, and is detected in mononucleated myocytes. The beta RyR isoform appears within 24 hr after the initiation of myotube formation, which is earlier than anticipated from studies with intact embryonic muscle. Normal alpha RyR protein is not detected in cultured cn/cn muscle cells, whereas the beta RyR, the alpha 1-subunit of the dihydropyridine receptor, the sarcoplasmic reticulum Ca(2+)-ATPase, and calsequestrin are expressed at comparable levels in normal and mutant muscle cells. Calcium transients elicited by electrical stimulation, acetylcholine, and caffeine are similar in normal and cn/cn cultured myotubes and are blocked by ryanodine in both cell types. In addition, comparable L- and T-type calcium currents are observed in normal and mutant muscle cells, suggesting that both the alpha 1-subunit of the dihydropyridine receptor and the beta RyR in mutant muscle cells are functional. Normal and cn/cn muscle cells proliferate and form myotubes in a similar manner. These latter events do not appear to depend on sarcoplasmic reticulum calcium release, as they also occur in normal muscle cells in which calcium release is prevented by chronic treatment with 100 microM ryanodine. Both cn/cn and ryanodine-treated normal muscle cells exhibit morphological changes similar to those observed in intact cn/cn skeletal muscle. Thus, the mutant phenotype observed in ovo is partially expressed under low density culture conditions, and neither beta RyR protein nor its function appear to be capable of preventing the associated changes. PMID- 8219361 TI - Differentiation of mouse embryonic stem cells in vitro: III. Morphological evaluation of tissues developed after implantation of differentiated mouse embryoid bodies. AB - Mouse embryonic stem cells (ES) were allowed to differentiate in a liquid culture system. After 2-3 weeks, complex cystic embryoid bodies developed. These bodies were composed of several structures identified as cardiac muscle and yolk sac blood islands as well as cup-shape compartments containing a mixed population of hematopoietic stem cells. When these cystic embryoid bodies were implanted into adult mice, either subcutaneously or under the kidney capsule, they developed into various tissues. These included bone, blood vessels, cardiac muscle, nerves, and skin with hair follicles. In addition, highly differentiated, complicated tissues resembling intestinal epithelium with mucus glands or salivary glandular tissue were derived. The ES tissues from these in vitro developed embryoid bodies developed quickly within 2 to 3 weeks of implantation. This is in contrast to a minimal of 6 weeks for teratocarcinomas derived from embryonic carcinoma cells and/or the direct implantation of undifferentiated embryonic stem cells. Moreover, we found that there are different types of tissue developed upon different sites of implantation. The data suggest a local environment and/or growth factors are influential for ES tissue development. This system provides a possible means to purify and identify stem cells that give rise to specific tissues, and to study the factors regulating the commitment of these stem cells. PMID- 8219362 TI - The Etl-1 gene encodes a nuclear protein differentially expressed during early mouse development. AB - Recently, we isolated a novel mouse gene, Etl-1 (Enhancer-trap-locus-1), whose deduced amino acid sequence shows in its C-terminal portion striking homology to the brahma protein (BRM), a transcriptional regulator of homeotic genes in Drosophila, and to SNF2/SWI2, a transcriptional regulator of various genes in Saccharomyces cerevisiae. Here we report the generation of antibodies against the Etl-1 gene product (ETL-1) and describe the subcellular localization as well as the expression and distribution of the ETL-1 protein during mouse pre- and early post-implantation development. ETL-1 is a nuclear protein and is expressed in a biphasic manner during early embryogenesis. Moderate levels of ETL-1 were detected in unfertilized and fertilized eggs but in the latter the protein was not concentrated in the pronuclei and seemed evenly distributed throughout the cytoplasm. In two-cell embryos nuclear ETL-1 protein accumulated transiently and levels decreased during subsequent cleavage development. After the morula stage, ETL-1 levels increased again; in blastocysts high levels of ETL-1 were present in inner cell mass cells whereas trophectoderm cells contained little or no ETL-1. During subsequent development essentially all cell types except parietal endoderm and trophoblast cells contained high levels of ETL-1. Our results imply that nuclear ETL-1 is dispensable for the progression to the two cell stage, and suggest that during cleavage ETL-1 might be needed at the onset of embryonic transcription. In blastocysts ETL-1 function might be specifically required in cells of the inner cell mass and later in most cells of the embryo proper and extraembryonic ectoderm lineage. PMID- 8219363 TI - The DCCT--finally!! PMID- 8219364 TI - Severe hypoglycemia in children and adolescents with IDDM: frequency and associated factors. AB - Severe hypoglycemia is a very common complication in youths with insulin dependent diabetes mellitus (IDDM). Seventy four children and adolescents were surveyed for a 1-year period to evaluate the frequency and associated factors of severe hypoglycemia. Patients or their parents completed a standardized questionnaire which inquired about severe and mild episodes, treatment, and prevention of hypoglycemia. Forty-four percent of the patients experienced at least one severe hypoglycemic episode [need for assistance (grade III), loss of consciousness with or without convulsions (grade IV)] during the survey period. The event rate was 0.77 episodes (grade III and IV) per patient-year. The group with severe hypoglycemic episodes was significantly older (mean age, 16.3 years; SD, 3.6 years versus mean age 13.7 years; SD, 4.9 years; p = 0.01) and had significantly longer duration of diabetes (mean, 8.2 years; SD, 4.3 years versus mean, 6.1 years; SD, 4.0 years; p = 0.04) than the group without severe hypoglycemic episodes. There were no significant differences in mean glycosylated hemoglobin (HbA1c), daily doses of insulin, type of insulin regimen, gender, and age at diagnosis between patients who reported severe episodes and those who did not. Mild hypoglycemia was reported by 72 patients. Fifty percent of the patients recognized potential precipitating factors. Older age and longer duration of diabetes seem to predispose the patient to severe hypoglycemia. This may be the result of a diminution of the counterregulation system including lower neuroadrenergic reaction, or the still unphysiologic treatment of diabetes. Continued vigilance and education is important in older adolescents with longer duration of diabetes. PMID- 8219365 TI - Bilateral infarction of the vastus lateralis muscle in a diabetic patient: a case report and review of the literature. PMID- 8219366 TI - Aldose reductase inhibition by ponalrestat (statil) does not prevent proteinuria in long-term diabetic rats. AB - The aldose reductase pathway has been implicated in the development of chronic complications of diabetes. In this study, we investigated the effect of an aldose reductase inhibitor, statil, on glomerular synthesis of heparan sulfate and albuminuria in male Wistar rats made diabetic with streptozotocin. Heparan sulfate is the predominant glycosaminoglycan (GAG) proteoglycan in the glomerular basement membrane (GBM). It confers a negative charge on the GBM, and its loss has been related to the presence of albumin in the urine. Diabetic rats synthesized less glomerular heparan sulfate and excreted more albumin than normal rats. Glomerular sorbitol concentration was significantly higher in diabetic than in normal rats. Chronic treatment of diabetic rats with statil did not improve either heparan sulfate synthesis or albuminuria despite normalization of glomerular sorbitol content. The present study does not support the role of excess sorbitol in the development of glomerular abnormalities in this rat model of streptozotocin diabetes. PMID- 8219367 TI - Capillary basement membrane in retina, kidney, and muscle of diabetic dogs and galactosemic dogs and its response to 5 years aldose reductase inhibition. AB - Capillary basement membrane thickening has been compared in retina, renal glomerulus, and leg muscle of dogs alloxan-diabetic 5 years and dogs experimentally galactosemic 5 years, and the effects of inhibition of aldose reductase have been examined. Basement membrane in each site became thickened as a result of either galactosemia or diabetes, but showed appreciable variation among the sites. The thickening of basement membrane in retina and muscle of galactosemic animals was similar in quantity and appearance to that seen in the diabetics, notwithstanding large differences between the two animal models with respect to tissue polyol concentrations and nonenzymatic glycation of hemoglobin and plasma protein. Aldose reductase inhibition was without influence on capillary basement membrane thickening in each tissue from dogs diabetic or galactosemic 5 years, despite substantial polyol path inhibition. PMID- 8219368 TI - Non-insulin-dependent diabetes mellitus and elevated serum ferritin level. AB - An elevated serum ferritin concentration recently has been shown to be associated with coronary artery disease and its risk factors, including blood glucose concentration. The purpose of this study is to establish the prevalence of elevated levels of serum ferritin in patients with non-insulin-dependent diabetes mellitus (NIDDM) without hemochromatosis and to determine whether or not deferoxamine is of therapeutic value in treating such patients. The level of serum ferritin was measured in consecutive eligible patients with NIDDM seen at routine outpatient visits. Five patients with an elevated serum ferritin were treated with deferoxamine, 1 g intramuscularly, twice a week for 12 weeks. The level of serum ferritin was measured every 4 weeks, and the level of glycosylated hemoglobin was measured at baseline, at the end of the treatment, and 12 weeks after treatment was completed. The level of serum ferritin was elevated in 34 of 102 (33%) patients with NIDDM. The level of serum ferritin remained elevated in 30 of 32 (94%) of these patients on repeat testing. In three of the five patients treated with deferoxamine, the level of serum ferritin was normalized, but no patient had an appreciable change in dosage of medication for diabetes or glycemic control. Non-insulin-dependent diabetes is a condition frequently associated with elevated levels of serum ferritin. Treatment with deferoxamine intramuscularly was not effective in improving control of glucose in our patient group. PMID- 8219369 TI - Diabetes and the risk of stroke. AB - Diabetes is an important risk factor for the development of ischemic cerebrovascular disease or stroke. Diabetic patients are more susceptible to atherothromboembolic brain infarction and its consequent mortality than nondiabetic patients. Cerebrovascular disease in the diabetic population somewhat follows the same pattern as in the nondiabetic population, however, with greater severity in outcome for the former. The etiopathogenetic mechanisms of strokes and transient ischemic attacks in diabetic patients are apparently due to cerebral hemodynamic and vascular derangements, hyperglycemia, and other related risk factors. There is a great disparity in the wider information on coronary heart disease and stroke than on diabetes and stroke. A better understanding is required for the determinants of stroke and diabetes, and the epidemiology and pathophysiology of specific risk factors in different racial groups. There is a similarity in the evaluation, assessment, and management of diabetic and nondiabetic patients. PMID- 8219370 TI - Introduction to mammalian salivary glands. PMID- 8219371 TI - Serous, seromucous, and special serous cells in salivary glands. PMID- 8219372 TI - Structure of serous cells in salivary glands. PMID- 8219373 TI - Structure of mucous cells in salivary glands. PMID- 8219374 TI - 3D-structure of cells of human salivary glands as seen by SEM. AB - To demonstrate by SEM the topography and cytoarchitecture of the different parenchymal components of human salivary glands, we have employed a number of techniques that allow either the exposure of internal and lateral cell surfaces or, following the removal of connective tissue, the visualization of endpieces, ducts, and myoepithelial cells. Serous glands consist of indented acini attached to the ducts in a grape-like fashion, whereas mucous and mixed glands are made up of smooth tubuli. Myoepithelial cells (mecs), which are abundant on the surfaces of acini, tubuli, and intercalated ducts, are sparse on striated ducts. They are star-shaped on acini, striated ducts, and most of the tubuli. Spindle-shaped mecs are seen, instead, on intercalated ducts and, occasionally, on mucous and mixed tubuli as well. Cells of striated ducts split into a number of large basal portions whose surface is covered by long laminated processes responsible for the striations seen with TEM. Excretory ducts are lined by small cup-shaped basal cells and by tall cylindrical cells, which are completely covered by short processes oriented at random. When observed from below, after removal of the basal lamina, the basal surfaces of cells of excretory ducts exhibit polygonal areas delimited by short reliefs. Those of striated ducts show, instead, long laminar processes arranged radially. Results presented here are discussed and put in relationship to the mechanism of saliva production. PMID- 8219375 TI - Structure of the duct system in mammalian major salivary glands. PMID- 8219376 TI - The innervation of salivary glands as revealed by morphological methods. AB - Salivary secretion is nerve mediated. The salivary glands are supplied by parasympathetic and sympathetic efferent nerves which travel to the glands by separate routes. Once in the glands the axons from each type of nerve intermingle and travel together in association with Schwann cells, forming Schwann-axon bundles. Two types of neuro-effector relationships exist with salivary parenchymal and myoepithelial cells: epilemmal (outside the parenchymal basement membrane) and hypolemmal (within the parenchymal basement membrane). Their relative frequencies with either type of nerve differ greatly between glands and species. Salivary blood vessels receive epilemmal innervations by both sympathetic and parasympathetic axons. The classical transmitters--acetylcholine in parasympathetic and noradrenaline in sympathetic axons--are stored in small vesicles. A variety of non-conventional neuropeptide transmitters have also been found in salivary nerves by immunohistochemistry, and they occur in large dense cored vesicles. Prolonged high frequency stimulation has been found to cause depletion of large dense-cored vesicles from glandular nerves. In recent years afferent nerves have started to be identified and are found in greatest numbers around the main salivary ducts, where they may form a hypolemmal association with the epithelial cells. Functional studies demonstrate complex interactions between parasympathetic and sympathetic nerves. Morphological assessments of changes in the parenchymal cells after nerve stimulations or denervations add greatly to our understanding of the nerve functions. At least four types of influence can be exerted on salivary parenchymal cells by the nerves: hydrokinetic (water mobilizing), proteokinetic (protein secreting), synthetic (inducing synthesis), and trophic (maintaining normal functional size and state). In respect to each role, wide glandular and species differences exist between the relative contributions made by each type of nerve. PMID- 8219377 TI - The taxonomy of depression. PMID- 8219378 TI - The naming of drugs. PMID- 8219379 TI - Overview of depression: chronicity, recurrence, morbidity and the need for maintenance treatment. PMID- 8219380 TI - The outcomes of juvenile-onset depression. PMID- 8219381 TI - Depression in medical patients. AB - Depression is a major problem in medical patients. It is a problem that has been generally under-recognized and under-treated, highly associated with somatized symptoms, loss of function, and increased medical utilization. Obviously more training needs to be provided in this area for non-psychiatric physicians, as well as other primary care providers. Much of what guides recognition and treatment of depression in medical patients has been derived from studies of depression in non-medical populations. However, it is not completely clear that depression in medical populations is the same problem as that seen in the mental health care setting. Furthermore, the majority of psychopharmacology studies have been done in patients with no medical conditions. There are, fortunately, increasing numbers of drug and ECT studies in specific medical populations as well as outcome studies in medically ill depressed patients. There has been increasing recognition that in the primary care setting, less severe depressive symptom constellations are a common problem. This so-called "sub-syndromal" depression is an area of great interest but little understanding. There is no well researched information on such depressions in terms of natural course, response to treatment, or relation to other disorders such as anxiety disorders. It is hoped that non-psychiatric physicians will increasingly recognize depression in their patients and feel comfortable in its evaluation and initial management. Clinical practice guidelines, which may be helpful to primary care physicians, are currently being developed. When patients seem difficult to manage or diagnose, consultation should be sought from psychiatrists familiar with the special presentations and problems of working with this population. PMID- 8219382 TI - Bipolar disorder for the non-specialist: clinical features, morbidity, and management strategies. PMID- 8219383 TI - Personality disorders and depression: an overview of issues and findings. PMID- 8219384 TI - Depression and substance abuse. PMID- 8219385 TI - Combined psychopharmacological and psychosocial treatment for depression. PMID- 8219386 TI - Neuropsychiatric aspects of depression. PMID- 8219387 TI - Anomalous increase in reported deaths, March 1993, Rhode Island. PMID- 8219388 TI - The specter of AIDS. PMID- 8219389 TI - Maladies unknown to our forefathers. PMID- 8219390 TI - From triptychs to T-shirts. PMID- 8219391 TI - Physicians and suspected rabies. PMID- 8219392 TI - AIDS in the '90s: increasing clinical challenges and constructive responses. PMID- 8219393 TI - The face of AIDS in Rhode Island: public health goals for the 1990s. PMID- 8219394 TI - Federal/state expenditures for HIV/AIDS services. PMID- 8219395 TI - The management of HIV-infected patients by primary care providers. PMID- 8219396 TI - HIV infection in Rhode Island women. PMID- 8219397 TI - Essentials of pediatric AIDS. PMID- 8219398 TI - HIV clinical trials in Rhode Island. PMID- 8219399 TI - Knowledge, attitudes, and beliefs concerning AIDS and HIV. PMID- 8219400 TI - Epidemiology of alcoholic liver disease. AB - Although mortality from alcoholic liver disease has declined in some Western countries in recent years, elsewhere it is increasing and overall it remains a major health problem. Deaths are predominantly seen in patients with alcoholic hepatitis or cirrhosis, and when they occur in patients with fatty liver are usually unrelated to liver disease. Progression to cirrhosis is correlated with the severity of fatty liver and particularly with the presence of alcoholic hepatitis. Mortality from cirrhosis is strongly correlated with per capita alcohol consumption. The decline in cirrhosis mortality rates seen recently is related in part to decreases in per capita consumption, but probably also to the growth of self-help organizations which facilitate abstinence from alcohol. Recent studies suggest there is not an invariable dose-response relationship between alcohol intake and the severity of liver disease and that alcohol has a permissive effect which allows other aetiological factors to operate. Factors that influence susceptibility to alcoholic liver disease include gender (women develop alcoholic cirrhosis more readily than men), concomitant hepatitis C infection and possibly hepatitis B infection. It is uncertain whether HLA status or immune mechanisms are implicated. The systematic use of screening tests for hazardous consumption combined with early intervention therapies offers a good prospect of reducing morbidity and mortality from alcoholic liver disease. PMID- 8219401 TI - Aetiology and pathogenesis of alcoholic liver disease. AB - Until the 1960s, liver disease of the alcoholic patient was attributed exclusively to dietary deficiencies. Since then, however, our understanding of the impact of alcoholism on nutritional status has undergone a progressive evolution. Alcohol, because of its high energy content, was at first perceived to act exclusively as 'empty calories' displacing other nutrients in the diet, and causing primary malnutrition through decreased intake of essential nutrients. With improvement in the overall nutrition of the population, the role of primary malnutrition waned and secondary malnutrition was emphasized as a result of a better understanding of maldigestion and malabsorption caused by chronic alcohol consumption and various diseases associated with chronic alcoholism. At the same time, the concept of the direct toxicity of alcohol came to the forefront as an explanation for the widespread cellular injury. Some of the hepatotoxicity was found to result from the metabolic disturbances associated with the oxidation of ethanol via the liver alcohol dehydrogenase (ADH) pathway and the redox changes produced by the generated NADH, which in turn affects the metabolism of lipids, carbohydrates, proteins and purines. Exaggeration of the redox change by the relative hypoxia which prevails physiologically in the perivenular zone contributes to the exacerbation of the ethanol-induced lesions in zone 3. In addition to ADH, ethanol can be oxidized by liver microsomes: studies over the last twenty years have culminated in the molecular elucidation of the ethanol inducible cytochrome P450IIE1 (CYP2E1) which contributes not only to ethanol metabolism and tolerance, but also to the selective hepatic perivenular toxicity of various xenobiotics. Their activation by CYP2E1 now provides an understanding for the increased susceptibility of the heavy drinker to the toxicity of industrial solvents, anaesthetic agents, commonly prescribed drugs, 'over the counter' analgesics, chemical carcinogens and even nutritional factors such as vitamin A. Ethanol causes not only vitamin A depletion but it also enhances its hepatotoxicity. Furthermore, induction of the microsomal pathway contributes to increased acetaldehyde generation, with formation of protein adducts, resulting in antibody production, enzyme inactivation and decreased DNA repair; it is also associated with a striking impairment of the capacity of the liver to utilize oxygen. Moreover, acetaldehyde promotes glutathione depletion, free-radical mediated toxicity and lipid peroxidation. In addition, acetaldehyde affects hepatic collagen synthesis: both in vivo and in vitro (in cultured myofibroblasts and lipocytes), ethanol and its metabolite acetaldehyde were found to increase collagen accumulation and mRNA levels for collagen. This new understanding of the pathogenesis of alcoholic liver disease may eventually improve therapy with drugs and nutrients. PMID- 8219402 TI - Animal models of alcoholic liver disease. PMID- 8219403 TI - Clinical features of alcoholic liver disease. AB - The severity and range of histological liver lesions caused by alcohol abuse varies considerably; these lesions are not specific for alcoholic damage, and diagnosis of alcoholic liver disease depends on obtaining an adequate history of prolonged alcohol abuse and on excluding other known causes of liver disease. The clinical features of alcoholic liver disease vary greatly and they have been classified into various syndromes. However, the syndromes overlap, the histological features underlying them also overlap and they represent part of a wide clinical spectrum. Alcoholic fatty liver occurs more in younger patients and has a much better prognosis than alcoholic hepatitis or alcoholic cirrhosis, but the previous view that alcoholic fatty liver is an innocuous lesion can no longer be maintained. Alcoholic hepatitis and alcoholic cirrhosis cause more severe syndromes and more florid clinical features, and mortality is related to features of liver failure and variceal bleeding. Abstinence is the only means of ensuring the best possible survival. PMID- 8219404 TI - Pathology of alcoholic liver disease. PMID- 8219405 TI - Investigation of alcoholic liver disease. AB - In heavy drinkers with clinical evidence of liver disease, routine investigations should exclude the possibility of other chronic liver diseases of non-alcoholic aetiology requiring specific therapy--these include chronic viral hepatitis, autoimmune diseases of the liver, Wilson's disease and genetic haemochromatosis. If abnormalities in liver biochemistry persist despite abstinence, or if the diagnosis of alcoholic liver disease is in doubt, a liver biopsy should be carried out. Studies evaluating the role of liver biopsy in alcoholic liver disease suggest that without histological confirmation the diagnosis will be inaccurate in 10-20% of patients. Serum biochemistry and the currently available imaging modalities have severe limitations in determining the relative contributions of fatty liver, alcoholic hepatitis and cirrhosis to the overall picture in alcoholic liver disease. Histological examination is therefore of additional value in determining the prognosis, which is worst in patients with a combination of alcoholic hepatitis and cirrhosis. There are a number of indices available, based on clinical and laboratory information, for evaluating the short term prognosis, but these can only be used with accuracy if the histological pattern of damage has initially been evaluated. PMID- 8219406 TI - Extrahepatic manifestations of alcoholic liver disease. AB - Many of the extrahepatic manifestations of alcoholic liver disease are not specific and can be seen in other forms of cirrhosis and with alcohol abuse. Features that are more common or more florid in patients with alcoholic liver disease have been discussed in this chapter. Alcoholic liver disease results in changes in many systems in the body and it is important that these are recognized and treated where appropriate. PMID- 8219407 TI - Medical treatment for alcoholic liver disease. AB - The most effective treatment for alcoholic liver disease is abstinence from alcohol and it is the only treatment for patients with alcoholic fatty liver. Although many empirical therapeutic agents have been studied in the short-term and long-term treatment of alcoholic hepatitis, results have been mainly inconclusive. To date, only corticosteroids have proved to decrease the short term mortality rate of patients with severe forms of acute alcoholic hepatitis. Corticosteroids are not beneficial to the majority of patients with mild or moderate forms of acute alcoholic hepatitis; such patients improve with abstinence from alcohol and general supportive measures and do not need a specific short-term treatment. Most long-term trials have only showed that most patients with alcoholic liver disease were neither abstinent nor compliant, and that long-term survival was strongly correlated to abstinence from alcohol. In one study, propylthiouracil decreased the long-term mortality rate of compliant patients with severe alcoholic liver disease who reduced their alcohol intake; however, further clinical trials are needed before propylthiouracil can be recommended. In another study, colchicine decreased the long-term mortality rate of cirrhotic patients, 45% of whom had alcoholic cirrhosis. Results were highly significant, and the need for further clinical trials of colchicine in the long term treatment of alcoholic and non-alcoholic cirrhosis is imperative. Enteral nutrition should also be studied in severely malnourished cirrhotic patients, since it was shown to decrease the short-term mortality rate of such patients in a recent study. PMID- 8219408 TI - Liver transplantation for alcoholic liver disease. AB - The role of liver transplantation as a treatment for end-stage liver disease occurring in alcoholic patients is controversial. Earlier predictions that survival of alcoholic patients after liver transplantation was worse than that of non-alcoholic liver graft recipients, or that few alcoholic patients with serious liver disease could meet stringent selection criteria, have proved false. As a result, in many liver transplant programmes, alcoholic liver disease constitutes one of the most common diagnoses among patients proceeding to transplantation. Survival of alcoholic patients after transplantation is similar to that in non alcoholic patients, i.e. up to 80% or more alive at 1 year. A multidisciplinary selection process has been introduced which includes careful psychiatric assessment to try to identify those patients most likely to maintain long-term abstinence after transplantation. Using this method, approximately 45% of alcoholic patients referred for transplantation have been selected for surgery. Furthermore, the survival rate of alcoholic patients not selected for transplantation because they were considered a poor prognostic risk for sobriety was significantly less than that of alcoholic patients undergoing liver transplantation. The ethical foundations for this multidisciplinary approach are explained in this chapter. Good data on recidivism after transplantation are few. In many programmes, including ours, instances of recidivism, defined as a relapse to a pathologic pattern of alcohol use, are uncommon and occur in 10% or less of alcoholic patients selected for liver transplantation, at least in the first 3 postoperative years. This figure underestimates the incidence of consumption of small amounts of alcohol. The data are limited also by the relatively short period of follow-up in most studies published to date. Whether recidivism will become more common as more patients are followed beyond 3 years remains to be seen. PMID- 8219409 TI - The prevention of alcoholic liver disease. PMID- 8219410 TI - Acetylcholinesterase staining and choline acetyltransferase activity in the young adult rat spleen: lack of evidence for cholinergic innervation. AB - Acetylcholinesterase (AChE) staining in spleens from young adult Sprague-Dawley rats was examined following several denervation paradigms to determine the source of splenic AChE+ nerve fibers. In spleens from all control groups, AChE+ neural like profiles were present along the vasculature and in the trabeculae. AChE+ reactivity also was present in lymphoid and reticular cells in the spleen, and in neuronal cell bodies in the superior mesenteric-coeliac ganglion (SM-CG). Neurochemical analysis revealed no significant choline acetyltransferase activity in spleens from control animals. Surgical removal of the SM-CG resulted in a total loss of both noradrenergic (NA) and AChE+ nerve profiles, as well as a loss of AChE staining in nonneural compartment in the spleen. On Days 1 and 3 after treatment, chemical sympathectomy with 6-hydroxydopamine also resulted in a loss of both NA and AChE nerve profiles in the spleen, except for a few resistant fibers in the hilar region. AChE reactivity in nonneural compartments also was diminished in chemically denervated regions of the spleen. AChE staining in both neural and nonneural profiles progressively increased from 10 to 56 days after chemical sympathectomy, with a time course and distribution pattern similar to NA fibers reinnervating the spleen. AChE+ staining was preserved following bilateral vagal nerve transection. The miniscule splenic levels of choline acetyltransferase suggest that at best, only a small density of cholinergic nerves distribute to the rat spleen. Further, what cholinergic innervation is present does not arise from the vagus nerve as suggested in the earlier literature. Collectively, the overlapping distribution of AChE+ and NA nerve profiles in spleen and parallel loss of both population of nerve fibers following surgical and chemical sympathectomy support the presence of AChE in NA nerves colocalized with norepinephrine, and thus make AChE+ staining an inappropriate marker for cholinergic innervation in the rat spleen. PMID- 8219411 TI - Differential effects of ethanol in mouse lines genetically selected for high and low antibody production. AB - There is considerable evidence of a relationship between the central nervous system and the immune system, and that several drugs with primary action at the central nervous system can affect different immune responses. In an attempt to obtain a better understanding of the interaction between ethanol's effects and immune functions, we used two mouse lines selected according to their high (HGP) or low (LGP) antibody production. These animals were injected with ethanol (20% w/v, 3.6 g/kg, ip); the latency for the loss of the righting reflex (LORR) and the time for the recovery of the righting reflex (RORR) were measured. Body temperature of both lines was also recorded before the injections and at RORR. Blood samples were taken at RORR to determine blood ethanol concentration. The results showed that the HGP mice presented shorter latency for sleep, longer sleeping time, and lower blood ethanol levels than the LGP mice. These data suggest that the HGP line is more sensitive to the effects of ethanol, and provide an additional approach for studying interactions between the immune and the central nervous systems. PMID- 8219412 TI - Immunocompetence in the long sleep and short sleep mouse lines: baseline versus primed responses. AB - Two lines of mice which were selectively bred for high (Long Sleep; LS) and low (Short Sleep; SS) reactivities to a sedative dose of ethanol, are also differentiated by agents that act at the GABAA-receptor complex. Since this supramolecular complex may also modulate immune function, measures of immunity have been examined in these lines. In the present study the immune responsiveness before and after an allogeneic priming stimulus was investigated. Lower mitogen induced T-cell proliferation, mixed leukocyte reaction, and cytotoxic T lymphocyte activity were found in unprimed LS compared to unprimed SS mice. In contrast, the LS line exhibited a marked augmentation of these responses after priming, while the SS mice appeared unresponsive to this challenge. Addition of splenocytes or cell-free splenic cultures from primed mice to cultures from unprimed mice suggested that differences in priming-induced cell-to-cell interactions, rather than the release of a soluble helper factor(s) into the medium, are responsible for the marked augmentation of the secondary response in LS, compared to SS mice. Fewer T-helper and T-suppressor/cytotoxic cells were found in LS compared to SS mice, and this was unaffected by priming. These results extend previous findings demonstrating a higher natural killer cell activity and rate of tumor rejection in LS mice and suggest that these lines may be useful in studying the regulatory role of the GABAA complex in immune function. PMID- 8219413 TI - Alterations of immune status induced by the sympathetic nervous system: immunomodulatory effects of DMPP alone and in combination with morphine. AB - The aim of the present study was to explore the involvement of the sympathetic nervous system (SNS) in the immunomodulatory effects of morphine in Lewis rats and to assess the effects of alterations in SNS activity on immune status. In the first experiment, sympathetic tone was elevated by administering the ganglionic stimulant 1,1-dimethyl-4-phenylpiperazinium (DMPP) in doses of 0, 0.01, 0.1, and 1.0 mg/kg, sc, 5 min before the sc administration of 15 mg/kg morphine or saline. Animals were sacrificed 1 h after the morphine injection and multiple in vitro immune assays were then conducted. Although DMPP did not significantly enhance morphine's suppressive effects in the spleen and blood mitogen stimulation assays or the splenic natural killer (NK) cell assay, DMPP alone produced effects on immune status in saline-treated animals. Therefore, a second experiment was conducted to examine the immunomodulatory effects of increasing peripheral sympathetic outflow in greater detail. Animals were administered a wider dose range of DMPP (0, 0.005, 0.05, 0.5, and 5.0 mg/kg, sc) 30 min prior to sacrifice and an expanded repertoire of immune assays was conducted. DMPP dose-dependently suppressed the mitogenic responsiveness of splenic T lymphocytes, splenic NK cell activity, and interleukin-2 (IL-2) and gamma-interferon production by stimulated splenocytes. DMPP did not alter the total number of splenic leukocytes or the proliferative response of splenic B lymphocytes. In the mesenteric lymph nodes, DMPP had no effect on mitogenic responsiveness, the production of IL-2 or the total number of leukocytes. In the blood, however, DMPP increased mitogenic responsiveness at intermediate doses and decreased proliferation at higher doses. DMPP also dose-dependently decreased the number of blood leukocytes/ml. Taken together, these results indicate that increasing peripheral sympathetic outflow results in profound effects on immune status that depend upon the degree to which SNS activity is altered, the compartment of the immune system, and the lymphocyte subtype. PMID- 8219414 TI - Oral hairy leukoplakia--10 years on. AB - Oral hairy leukoplakia (OHL) was first observed in 1981 and reported in 1984. Initially, this entity was restricted to HIV-seropositive male homosexual patients, but the risk group has been expanded since 1986 to all patients infected with HIV. It has been recognized that OHL is caused by Epstein-Barr virus (EBV). In 1988 we reported the first HIV-negative immunosuppressed patient with documented EBV-positive OHL. In patients with OHL, continuous shedding of EBV from saliva is necessary to maintain the lesion. EBV shedding leads to repeated infection of the intraoral epithelium. This may explain the highly variable course of OHL. The lesions may spontaneously disappear within few days. No latent EBV can be found in basal or suprabasal cells. In OHL coinfection with multiple strains of replicating EBV was documented recently. The clinical diagnosis of OHL may be confirmed by ultrastructural examination or in situ hybridization of exfoliative cytologic specimens. OHL is highly predictive for the development of AIDS. However, in HIV-seropositive patients, detection of EBV DNA in the oral epithelium by the scraping method may be an earlier and more powerful predictor of progression to AIDS than is OHL. PMID- 8219416 TI - KONCPA: a new method for diagnosing tinea unguium. AB - Tinea unguium (TU) is very common in tropical and subtropical regions. An inexpensive, quick and sensitive test is essential for screening the nail specimens. We investigated if a test using potassium hydroxide (KOH)-treated nail clippings, which were then crushed and stained with periodic acid-Schiff (PAS), could be useful for diagnosing TU. The new method (abbreviated as KONCPA) was proved to be more fruitful to identify fungal hyphae in comparison with conventional KOH nail scraping preparation, histopathologic examination and fungal culture. The positive rates of each method were 77, 44, 60 and 16%, respectively. All 10 KONCPA-negative nails failed to show fungus by the other three methods. The KONCPA slides can be permanently stored as records. In addition, we also found that treatment of nail specimens in 20% KOH at 56 degrees C for 10 min prior to histopathologic processing is a simple method to soften the nail plate. PMID- 8219415 TI - Risk of melanoma after treatment of pigmented lesions with Solcoderm. AB - A 40-year-old patient developed a 5-mm-deep melanoma from a lesion on her chest which had been treated with Solcoderm 10 years previously. We recently described 3 other cases of melanoma that evolved in a lesion treated by Solcoderm. Much debate surrounds the recommendation as to the appropriate method for treatment of pigmented lesions when the removal is indicated for cosmetic reasons only. Most of the authors agree that any pigmented lesion which merits excision merits submission for histological examination. The aim of the present report was to express a warning regarding what we think is an inappropriate and hazardous method of treating pigmented lesions, namely their chemical destruction with Solcoderm. In view of the reported cases of melanoma evolving in lesions treated previously with Solcoderm, we believe that this treatment is absolutely contraindicated for pigmented lesions. PMID- 8219417 TI - The Nageli-Franceschetti-Jadassohn syndrome: A hereditary ectodermal defect leading to colloid-amyloid formation in the dermis. AB - Light- and electron-microscopical examination of 4 skin biopsies from 2 members of the initially described family with Nageli-Franceschetti-Jadassohn syndrome revealed that the already reported pigment incontinence is accompanied by varying amounts of colloid-amyloid bodies located in the superficial dermis. Occasionally, such bodies could also be seen around sweat glands in the reticular dermis. These findings indicate that cutaneous colloid-amyloid formation could be a pathogenic factor in the phenotypic expression of this autosomal dominant syndrome. PMID- 8219418 TI - Sweat studies under conditions of moderate heat stress in two patients with the Nageli-Franceschetti-Jadassohn syndrome. AB - The sweating response of 2 patients with the Nageli-Franceschetti-Jadassohn syndrome was measured by direct calorimetry. During the experiment, under conditions of moderate heat stress, the 2 patients felt comfortable and showed a normal thermoregulatory response. This tended to corroborate the patients' history which did not reveal a clear-cut heat intolerance. However, the starch iodine test on the right flexor forearm revealed a marked reduction in activated sweat gland density while the patients were still under experimental conditions. Probably this was not the only region with a reduced number of functioning glands. Still, the patients' overall performance through the experiment indicated that their total number of functioning glands was able to produce a sweat output sufficient to prevent disturbances in thermoregulation. To our knowledge, this is the first study of the thermoregulatory capacity of patients suffering from a hereditary dermatosis in which hypohidrosis is part of the clinical picture. PMID- 8219419 TI - Systemic sclerosis (scleroderma) associated with discoid lupus erythematosus. AB - Six patients with systemic sclerosis (SS) and discoid lupus erythematosus (DLE) were studied to determine whether such cases have some common clinical and laboratory findings. DLE preceded SS in all cases. Three patients had diffuse scleroderma with lung and esophagus involvements and the others limited scleroderma. Three patients had anti-topoisomerase-I and antiribonucleoprotein antibodies, 2 had either of them and the remaining anticentromere antibodies. Four had DLE located on the scalp, leading to alopecia. The other 2 had DLE on the face and extremities. No case fulfilled criteria for systemic lupus erythematosus (SLE). The present cases with SS and DLE, but without SLE, indicate that this type of systemic-cutaneous collagen disease overlap does exist and may be not so rare. PMID- 8219420 TI - Cutaneous late-phase reaction to environmental antigen in patients with atopic dermatitis. AB - Intradermal testing with 7 environmental allergens was performed on 71 patients with atopic dermatitis (AD) with respiratory atopy (RAT) and 30 pure AD patients, and the cutaneous late-phase reaction (CLPR) was observed several to 48 h after challenge. CLPR was not seen in pure AD. In AD patients with RAT, CLPR was positive in 29 of 71 patients. No macroscopic eczematous lesions appeared. All CLPR-positive patients showed RAST scores of 2 or more. We assume that CLPR can be an exacerbating factor in AD with RAT, while it is not directly involved in pure AD. PMID- 8219421 TI - Histocompatibility antigens in vitiligo: Hamburg study on 102 patients from northern Germany. AB - One-hundred and two patients from the area of Hamburg, Germany, with vitiligo (photo-skin types II and III, Fitzpatrick classification, 1979), were examined for a possible association of the human lymphocyte antigen (HLA) complex with this disease. Antisera panels for the detection of 75 HLA antigens were utilized for this HLA typing (WHO Bulletin, 1988). The results were compared with 400 unrelated age- and sex-matched controls with photo-skin types II and III from the same geographical area. Nine of 76 vitiligo patients showed a significantly increased expression of the rare antigen HLA DRW12 (pc = 0.000708), and 65/102 patients showed a marginally significant increased frequency of HLA A2 (pc = 0.04850) compared with controls. For HLA BW60 (40), a significant increase in frequency was shown only in the adult vitiligo group (pc = 0.0126). A 'preventive' antigen for the manifestation of vitiligo has not been identified in this study. A comparative analysis of all published data on the possible association of HLA with vitiligo does not support a definitive linkage to the MHC so far. PMID- 8219422 TI - Oral trimethoprim as a third-line antibiotic in the management of acne vulgaris. AB - Acne vulgaris usually improves with long-term oral antibiotic therapy; however, some patients fail or only partially respond to the commonly prescribed antibiotics. Only a proportion of these patients warrants treatment with isotretinoin suggesting a need for additional therapeutic options. We have therefore performed an open retrospective study of the efficacy of trimethoprim as a third-line antibiotic in the treatment of patients whose acne vulgaris failed to respond to at least 2 courses of antibiotics. A total of 56 patients were reviewed, who had all failed to respond adequately to a minimum of 2 courses of antibiotics. All patients received trimethoprim in a dosage of 300 mg twice daily for at least 4 months, unless it had been withdrawn due to side effects. Topically they were given 1% clindamycin lotion twice daily to the affected areas. The severity of the patient's acne was graded on the face, back and chest. The changes in acne grades were evaluated using non-parametric statistics (Wilcoxon matched pairs). At 4 months there were significant improvements from the grades at initiation in all three sites (p = 0.005 or less). Twenty-one patients remained on the treatment for 8 months, and a significant improvement in the changes of the acne grades remained (p = 0.02 or less). Two patients had the trimethoprim stopped due to side effects. We can therefore recommend this regime as a third-line treatment in the management of acne. PMID- 8219423 TI - Nail bleeding associated with neurological diseases: all that uncommon? Report of 3 cases. AB - We report 3 patients, without bleeding disorders, presenting with onychomadesis and focal haemorrhages at multiple proximal nail folds or in the nail tissue. In one of our patients it was possible to check the appearance of a drop of blood on each side, beneath the proximal nail fold when he pressed the pulp of the fingers of his previously fractured forearm on a hard surface. All patients had major peripheral or major peripheral and central neurological deficits, prior to the nail bleeding. Peripheral vascular dilatation produced by paralysis of the vasoconstrictors in the nail area slows the venous return in the dilated vessels, mainly in the proximal nail fold. PMID- 8219424 TI - Spontaneous resolution of keratosis lichenoides chronica. AB - Keratosis lichenoides chronica (KLC) is a disorder of keratinization with a chronic progressive course. The nosology of this disorder has been discussed in relation to lichen planus. In this communication a classical case of KLC is presented; however, the lesions involuted spontaneously. The present observation challenges the common belief that KLC has a chronic progressive course. PMID- 8219425 TI - Adams-Oliver syndrome: cutis marmorata teleangiectatica congenita with multiple anomalies. AB - A 1-year-old female with the following multiple congenital anomalies is described: large vascular plaques on the scalp with atrophy and ulcerations, cutis marmorata and dilated veins on the trunk and extremities, short toes with partially missing phalanges and nails, retro- and micrognathia, strabismus convergens and atrial septal defect. These anomalies are characteristic of the Adams-Oliver syndrome, a rare autosomal dominant neuroectodermal syndrome which may be a maximal variant of van Lohuizen's syndrome (cutis marmorata teleangiectatica congenita). PMID- 8219426 TI - Trichoepithelioma 100 years later: a case report supporting the use of radiotherapy. AB - Trichoepitheliomas are rare skin tumors which can cause significant cosmetic and functional impairment when they occur in the head and neck area. Multiple methods of treatment including plastic surgery, dermabrasion, cryosurgery and laser surgery have been reported in the literature. A 32-year-old male with multiple coalesced lesions in his ear canals was treated with radiation therapy after he failed more conventional methods of treatment. He is free of tumor in the radiated area 17.5 months after treatment with significant functional improvement. Various aspects of this tumor were reviewed. More data are still needed to define the proper place for radiation in the management of this disease. PMID- 8219427 TI - Hair follicle nevus: an entity of its own? PMID- 8219428 TI - Kobner phenomenon in a psoriatic patient under cyclosporin therapy after contusion trauma and local application of hyperaemic ointment. PMID- 8219429 TI - Acute exanthematous pustular dermatitis after pneumococcal vaccine. PMID- 8219430 TI - The Swiss Society of Dermatology and Venereology. 75th annual meeting: 80 years of activity. PMID- 8219431 TI - Randomized, controlled trial of transdermal clonidine for smoking cessation. AB - OBJECTIVE: To determine the efficacy and safety of clonidine versus placebo in smoking cessation. DESIGN: Single-center, randomized, double-blind, parallel design comparison of transdermal clonidine with behavior modification, transdermal clonidine without behavior modification, placebo with behavior modification, and placebo without behavior modification. SETTING: Outpatient, university-based ambulatory care facility. PATIENTS: One hundred fifty generally healthy, highly nicotine-dependent cigarette smokers. INTERVENTION: Clonidine was given as the transdermal patch initiated 72 hours prior to smoking-cessation attempts and continued for six weeks thereafter. Clonidine was given at a dose of 0.2 mg/d for patients weighing more than 150 pounds (> 67.5 kg) and at a dose of 0.1 mg/d for patients weighing less than 150 pounds (< 67.5 kg). Behavior modification consisted of a total of 12 one-hour structured group training sessions. Patients not receiving behavior modification received printed material, which included the "Help Quit Kit" and the "I Quit Kit" from the American Cancer Society. MAIN OUTCOME MEASURES: Smoking-cessation rates were assessed at 6, 12, 24, and 52 weeks of follow-up. In addition, adverse reactions to clonidine or placebo were evaluated. RESULTS: Clonidine with behavior modification was statistically superior to the other three treatment groups but only at 6 weeks of follow-up. There were no differences in smoking-cessation rates among any of the treatment groups at any other follow-up intervals. Patients receiving behavior modification, regardless of whether they received clonidine, had better quit rates than patients not receiving behavior modification at all follow-up times except 52 weeks. Women receiving clonidine had significantly better quit rates than men receiving clonidine at all follow-up visits. Clonidine was associated with a significantly higher incidence of adverse effects than placebo (52 vs. 11 percent). However, the number of smokers withdrawing from the study was not greater with clonidine compared with placebo (9 vs. 7 percent, respectively). CONCLUSIONS: Clonidine is probably not effective as a pharmacologic adjunct to behavior modification in smoking cessation. It may have a potential role in women smokers who do not respond to or cannot tolerate more traditional smoking cessation therapies. PMID- 8219432 TI - Pharmacokinetics of pravastatin in elderly versus young men and women. AB - OBJECTIVE: To assess the effect of age on the pharmacokinetics of pravastatin in men and women. A secondary objective was to evaluate the effect of oral contraceptive steroids on the pharmacokinetics of pravastatin in young women. DESIGN: Open, single-dose study. SETTING: Clinical Pharmacology Unit of Princeton Medical Center for study in men and Hill Top Pharmatest, Cincinnati, for study in women. PARTICIPANTS: Normal, healthy male (aged 19-75 y) and female (aged 18-78 y) volunteers. INTERVENTIONS: Subjects received a single 20-mg dose of pravastatin after an overnight fast. MAIN OUTCOME MEASURES: The maximum plasma pravastatin concentration (Cmax), time required for that concentration to develop (Tmax), and the elimination half-life (beta t1/2). Serum concentrations of pravastatin and its major metabolite, the 3-alpha isomer, SQ 31,906, were determined at 12 intervals from 0.33 to 48 hours after the dose. Urine was collected cumulatively during the same period to determine urinary excretion of pravastatin and SQ 31,906. Both measures were used to determine pharmacokinetic parameters. RESULTS: The pharmacokinetic profiles of pravastatin and SQ 31,906 in young and elderly subjects of men and women differed little. Although the mean area under the concentration time curve of pravastatin was higher in the elderly and significantly higher in the elderly women, Cmax and beta t1/2 values were similar in the young and the elderly volunteers. Concomitant administration of oral contraceptives in young women did not affect the pharmacokinetics of pravastatin or SQ 31,906. CONCLUSIONS: The pharmacokinetics of pravastatin do not necessitate dosage adjustments in elderly men or women. No differences were detected between the disposition of the parent drug or its metabolite in men and women. PMID- 8219434 TI - Acute pulmonary edema after polyethylene glycol intestinal lavage in a child. AB - OBJECTIVE: To report the case of an eight-year-old girl, without preexisting cardiac or renal disease, who developed acute pulmonary edema and severe respiratory distress after balanced electrolyte with polyethylene glycol (BE-PEG) intestinal lavage. CASE SUMMARY: During the nasogastric infusion of a one-liter dose of BE-PEG (OCL, Abbott), the patient experienced abdominal discomfort, gagging, vomiting and coughing. After the nasogastric infusion, the patient again had emesis, developed tachypnea, intercostal retractions, and acute respiratory distress. She received oxygen and subsequently required intubation and ventilatory support. Physical examination revealed pulmonary congestion bilaterally but no signs of cardiac failure or sepsis. Chest X-ray revealed bilateral pulmonary edema. Ventilatory support was continued for 36 hours and the patient was extubated after two days. DISCUSSION: Enteral BE-PEG may have caused acute pulmonary edema secondary to aspiration or systemic fluid overload. Although the exact cause remains unknown, the close temporal onset of pulmonary edema after BE-PEG administration in an otherwise healthy child suggests a causal relationship. CONCLUSIONS: This case should alter clinicians to the potential for significant morbidity with BE-PEG solutions, particularly if used in outpatient settings. Patients who receive BE-PEG should be closely observed and monitored for potential aspiration, excessive infusion rates, and gastrointestinal symptoms to optimize efficacy and reduce morbidity. PMID- 8219433 TI - Lithium-induced parathyroid dysfunction: a case report and review of the literature. AB - OBJECTIVE: Twenty-six cases of lithium-induced hyperparathyroidism have been reported in the literature. This article describes an additional case that illustrates current management recommendations. DESIGN: Case report. Clinical presentation and proposed mechanisms of the suspected drug-induced effect are discussed. CONCLUSIONS: Serum calcium concentrations should be determined before and periodically during long-term lithium carbonate therapy. Discontinuation of therapy in patients who develop lithium-induced parathyroid dysfunction generally corrects calcium and parathyroid hormone concentrations. Surgery is indicated in patients with complications of hyperparathyroidism. PMID- 8219435 TI - Variability in plasma lipoprotein profiles when comparing diltiazem and propranolol. AB - OBJECTIVE: To examine the effects of diltiazem and propranolol on plasma lipoproteins in a double-blind, comparative trial. PATIENTS: Twenty-one mild-to moderate hypertensive patients. METHODS: Following discontinuation of previous antihypertensive treatments, and a 4-week, single-blind, placebo run-in, subjects were randomized to receive sustained-release diltiazem or propranolol. Total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), and very-low-density lipoproteins (VLDL) were measured during placebo administration and after 12-16 weeks of treatment. RESULTS: No significant changes in plasma lipoprotein concentrations were noted in either the diltiazem or propranolol group compared with baseline values or each other. Marked variation in HDL, LDL, and VLDL were noted following drug treatment and in eight subjects whose lipoprotein concentrations were remeasured prior to drug treatment during the placebo period. The alterations were bidirectional, and similar in magnitude to those found following drug treatment. CONCLUSIONS: In many cases, changes in plasma lipoproteins reported to be a consequence of antihypertensive treatment may merely reflect normal intrapatient variability. PMID- 8219436 TI - Renal insufficiency associated with intramuscular administration of ketorolac tromethamine. AB - OBJECTIVE: To evaluate reports of renal toxicity associated with intramuscular ketorolac tromethamine. Medical charts were reviewed for all cases of renal toxicity associated with ketorolac therapy. METHODS: Patients with possible ketorolac-associated nephrotoxicity were identified through our institution's adverse drug reaction reporting program. Patients were included in this report if: (1) renal insufficiency was temporally related to ketorolac administration; (2) resolution of renal insufficiency occurred after discontinuation of ketorolac; and (3) no other causes of renal insufficiency, including other medications, could be identified. RESULTS: Six patients had renal insufficiency secondary to ketorolac administration. The mean age of the patients was 58 years and cardiovascular disease was present in five. Serum creatinine values increased from a mean of 106 +/- 26 mumol/L (1.2 +/- 0.3 mg/dL) to a mean peak value of 256 +/- 195 mumol/L (2.9 +/- 2.2 mg/dL). Recovery of renal function was observed after a mean of 2.3 +/- 0.5 days. CONCLUSIONS: Short-term administration of ketorolac can be associated with reversible oliguric renal insufficiency. Indiscriminate use of ketorolac for pain management in place of narcotic analgesics should be avoided, especially in patients at high risk for toxicity induced by nonsteroidal antiinflammatory drugs. PMID- 8219437 TI - Neurologic adverse effects during concomitant treatment with ciprofloxacin, NSAIDS, and chloroquine: possible drug interaction. AB - OBJECTIVE: To report a case of neurologic adverse effects that developed during concomitant treatment with ciprofloxacin, nonsteroidal antiinflammatory drugs (NSAIDs), and chloroquine. Possible mechanisms for a drug interaction are discussed. CASE SUMMARY: A 68-year-old woman who was receiving chronic treatment with NSAIDs and chloroquine developed dizziness, anxiety, and tremors when ciprofloxacin 500 mg twice daily was begun for Salmonella osteitis. When she discontinued the antirheumatic treatment, there was a prompt relief of symptoms. After indomethacin was reintroduced, the patient developed signs and symptoms of peripheral neuropathy, which partially subsided when ciprofloxacin was discontinued. DISCUSSION: Enhanced neurologic adverse effects of ciprofloxacin when taken together with NSAIDs or chloroquine may result from reduced effects of gamma-aminobutyric acid. An alternative explanation could be that NSAIDs and chloroquine impair the elimination of ciprofloxacin, thereby contributing to toxic concentrations of the antibiotic. CONCLUSIONS: The possibility of interactions between ciprofloxacin and antirheumatic drugs should be considered. PMID- 8219438 TI - Thrombotic thrombocytopenic purpura associated with ticlopidine. AB - OBJECTIVE: To report a case of possible ticlopidine-induced thrombotic thrombocytopenic purpura (TTP). CASE SUMMARY: A 68-year-old man was started on ticlopidine therapy for transient ischemic attack because of aspirin intolerance. Three weeks after starting therapy, the patient developed TTP, manifest by severe thrombocytopenia, renal failure, microangiopathic hemolytic anemia, and neurologic symptoms. The condition reversed over three to five days coincident with the discontinuation of ticlopidine and therapy with daily plasma infusion and exchange. No evidence of relapse was found at one-year follow-up. DISCUSSION: TTP is a well-defined clinical entity with varied etiologies. Ticlopidine has been reported as causing neutropenia and isolated thrombocytopenia. Case reports have linked ticlopidine to the development of TTP. CONCLUSIONS: Including this case there are now seven patients who have been documented as developing TTP while receiving ticlopidine. In addition to monitoring for neutropenia and isolated thrombocytopenia, patients receiving ticlopidine also should be monitored for the development of TTP. PMID- 8219439 TI - Antibiotic treatment of duodenal ulcers. PMID- 8219440 TI - Metronidazole/neomycin as preoperative bowel preparation. PMID- 8219441 TI - Fluoxetine in alcoholism. PMID- 8219442 TI - Tricyclic antidepressant withdrawal syndrome. AB - OBJECTIVE: To examine the evidence pointing to a withdrawal syndrome associated with the discontinuation of tricyclic antidepressants (TCAs). DATA SOURCES: MEDLINE searches were conducted. References used in relevant articles were screened for additional published information. STUDY SELECTION: Emphasis was placed on human trials and individual case reports. DATA SYNTHESIS: Symptoms of gastrointestinal and somatic distress, sleep disturbance, and movement disorders and mania have been temporally linked to withdrawal of TCAs. Cholinergic and adrenergic overdrive after TCA discontinuation have been suggested as the proposed mechanism for this syndrome. Reported symptoms may be psychosomatic or related to underlying mental illness. CONCLUSIONS: Clinicians should be aware that discontinuation of TCA therapy may produce a withdrawal syndrome in some patients. PMID- 8219443 TI - Felbamate. AB - OBJECTIVE: To provide an up-to-date review of the current literature on felbamate (FBM) and its use as an antiepileptic medication (AEM). DATA SOURCES: All published literature (manuscripts and abstracts) on FBM was reviewed. The initial bibliography (up to September 1992) was provided by the manufacturer (Carter Wallace Laboratories); subsequent literature was obtained from American Epilepsy Society presentations in December 1992 and manuscripts published up to January 1993. STUDY SELECTION/DATA EXTRACTION: All pertinent literature was reviewed. Information from the publications was abstracted and organized by the author. DATA SYNTHESIS: FBM is effective in complex partial seizures either as monotherapy or as an adjunct in patients receiving other AEMs. In addition, it has shown efficacy in some seizures associated with the Lennox-Gastaut syndrome. Adverse effects appear to be mild. When FBM is given as monotherapy, the primary adverse effects are insomnia and weight loss. Patients receiving multiple AEMs may have increased adverse effects. CONCLUSIONS: FBM appears to be an effective new AEM. Additional studies as to its role in newly diagnosed and pregnant patients are needed. Pharmacokinetic studies in children, patients with renal failure, and patients on nonepilepsy drugs also are needed. PMID- 8219444 TI - Review of in vitro activity, pharmacokinetic characteristics, safety, and clinical efficacy of cefprozil, a new oral cephalosporin. AB - OBJECTIVE: To review the pharmacokinetics, microbiology, clinical efficacy, safety, and tolerance of cefprozil, a new, broad-spectrum oral cephalosporin. DATA SOURCES: Published clinical trials and microbiologic, pharmacokinetic, and safety data were identified by MEDLINE; additional references were derived from bibliographies of these articles; microbiologic data on file were provided by Bristol-Myers Squibb. STUDY SELECTION: Only published comparative clinical trial reports are included in the review of clinical efficacy. Noncomparative clinical data pertaining to uses of cefprozil not approved by the Food and Drug Administration are not included. DATA SYNTHESIS: Data are presented on the in vitro microbiologic activity of cefprozil against 10,152 bacterial isolates, including most of the clinically important streptococci (e.g., Streptococcus pyogenes, Streptococcus pneumoniae), beta-lactamase-positive and -negative Staphylococcus aureus and Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Proteus mirabilis, Clostridium difficile, and numerous other gram-negative aerobes and anaerobes. In clinical trials, cefprozil appears to be at least as effective as commonly used comparison agents such as cefaclor, cefixime, and amoxicillin/clavulanic acid. Additionally, cefprozil is better tolerated than the latter two agents, especially with regard to gastrointestinal adverse effects. CONCLUSIONS: Cefprozil is a broad-spectrum cephalosporin that provides coverage against both gram-negative and -positive bacteria that may cause otitis media, pharyngitis/tonsillitis, skin and skin-structure infections, secondary bacterial infection of acute bronchitis, and acute bacterial exacerbations of chronic bronchitis. The beta-lactamase stability of cefprozil appears to exceed that of other oral cephalosporins for some important pathogens. Cefprozil is used primarily for second-line treatment as less-expensive, first line generic alternatives generally are available. Cefprozil demonstrates clinical advantages over many other orally administered beta-lactam antibiotics in terms of antimicrobial spectrum, a once- or twice-daily dosing regimen, and/or reduced incidence of adverse effects. PMID- 8219445 TI - Ticlopidine and antiplatelet therapy. AB - OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and toxicity of ticlopidine. Comparisons with other antiplatelet agents are presented, with an emphasis on efficacy, and a recommendation is provided regarding ticlopidine's place in therapy. DATA SOURCES: A MEDLINE literature retrieval of English-language journal articles from 1987 to January 1993 and references identified from bibliographies of review articles and clinical trials. STUDY SELECTION: Randomized, blind, controlled studies of ticlopidine and other antiplatelet agents were preferentially selected. DATA EXTRACTION: Clinical trials were reviewed in terms of study design, efficacy results, and toxicity. DATA SYNTHESIS: Ticlopidine is a new antiplatelet agent with a distinct mechanism of action. In the largest trial of the drug for the prevention of stroke, it was found to be more effective than aspirin in reducing the risk of stroke or death. Clinical trials have also shown ticlopidine to decrease the rate of vascular death and myocardial infarction in patients with unstable angina, and to maintain venous graft patency after coronary artery bypass grafting. The use of ticlopidine in diabetic microangiopathy and peripheral vascular disease appears promising, but further studies are needed. Adverse reactions most commonly reported with ticlopidine are gastrointestinal complaints; the most severe reaction is transient neutropenia, which is seen in approximately 2.3 percent of patients and is severe in nearly 1 percent. CONCLUSIONS: Ticlopidine is a reasonable alternative for use in preventing stroke among patients unable to take aspirin or those who do not benefit from aspirin therapy. Its use as first-line therapy is limited by its high cost and the occurrence of hematologic adverse effects. PMID- 8219446 TI - Clinical update on pentoxifylline therapy for diabetes-induced peripheral vascular disease. AB - OBJECTIVE: To introduce readers to the use of pentoxifylline for diabetes-induced peripheral vascular disease. The article provides background on the pathophysiology of diabetic foot ulcers as well as a review of the literature on the therapeutic use of pentoxifylline for treating this disorder. DATA SOURCES: A MEDLINE search was used to identify pertinent literature, including review articles and case reports. Key index terms included pentoxifylline, diabetic foot ulcer, neuropathy, peripheral vascular disease, and intermittent claudication DATA EXTRACTION: Basic pharmacologic data regarding absorption, distribution, metabolism, and excretion were reported in normal subjects as well as in patients with renal impairment. Open and controlled clinical trials also were analyzed; subjective symptoms were reported. The economic implications also were reported. The pharmacist's role in patient education is discussed. DATA SYNTHESIS: Pentoxifylline 800 mg/d was found to be effective in improving the symptoms in patients with noninsulin-dependent diabetes mellitus, including improvement in walking distance, paresthesia, skin temperature, and subjective overall response. In nondiabetic patients, statistically significant differences in leg-ulcer healing were found between the treatment and placebo groups. Case reports illustrated healing times, which ranged from two weeks to six months. Pentoxifylline use in both insulin-dependent and noninsulin-dependent patients was assessed in clinical trials, with improvement of symptoms in both patient types. CONCLUSIONS: Studies show that pentoxifylline is an alternative to vascular surgery in the management of peripheral vascular disease in diabetic patients, particularly in those with chronic ulceration of the lower extremities that does not heal despite other optimal treatment regimens, including cessation of smoking, maintenance of normoglycemia, elimination of vasoconstrictive drugs, correctly fitted shoes, and appropriate would care. Pentoxifylline therapy may provide an appropriate, economical treatment modality by reducing the need for hospitalization and vascular surgery. PMID- 8219447 TI - 1993 Bibliography: a 32-year literature review on the value and acceptance of ambulatory care provided by pharmacists. AB - OBJECTIVE: To review the published literature on the value and acceptance of pharmaceutical services provided by pharmacists in ambulatory care settings. DATA SOURCES AND METHODS: Articles published between 1960 and 1992. A MEDLINE search of the English-language literature was conducted using the terms pharmacists, services, and ambulatory settings. Studies were selected for inclusion if they addressed services provided by pharmacists in ambulatory settings and dealt with the cost of patient care, quality of care, or attitudinal surveys. Original research reports were summarized according to objectives, sample size, duration of study, methods, and findings. Summaries were categorized according to reported positive impact, negative impact, or investigational reports with no outcome. RESULTS: One hundred seventy articles were identified; 104 of them reported research data and were summarized. The 1970s was the most prolific decade for publication of articles reporting positive, negative, or no impact, which numbered 47, 20, and 37, respectively. Positive correlation was found among studies conducted according to predetermined protocol and reporting positive impact. Moreover, academic interest in pharmacy varied for the different decades. CONCLUSIONS: Collectively, this article provides references of the published reports on pharmacy professional services in ambulatory care settings, and a summary of the articles reporting research data. Additional and more focused research on pharmaceutical services in the community is needed. Emphasis is required on practicing pharmacists' attitudes toward nondispensing, patient oriented pharmaceutical services; the impact of educational changes on the practice of pharmacy and consumers' attitudes and willingness to pay for services; and the link between patient outcome and pharmaceutical services. PMID- 8219448 TI - Prescription drug use among ambulatory elderly in a Swedish municipality. AB - OBJECTIVE: To analyze prescription drug use among the elderly in a Swedish municipality. METHODS: The municipality of Tierp, located in mideastern Sweden, is a well-defined geographic area that includes both rural areas and a few small, industrial towns. All people aged 65 years and older (n = 4769) as of 1986 in a total population of 21,000 inhabitants were included in the study. Their drug use was studied by registering all prescriptions filled by the pharmacies in the area. RESULTS: Most of the elderly (> 70 percent) obtained at least one prescription during the year studied. Drug use was more common among women than men. However, the difference between men and women was much smaller among those aged 85 years or more. The drugs most commonly prescribed were cardiovascular, psychotropic, and analgesic agents. Furthermore, the study showed that simultaneous use of several drugs was quite common. One-fourth of all people aged 65 years and older used drugs from at least four different pharmacologic groups. CONCLUSIONS: Our results revealed widespread use of prescription drugs among the elderly. An important finding was extensive drug use among men aged 85 years or more. This age group is increasing and there is need for further studies of its medication use. PMID- 8219449 TI - Evaluation of pharmacoeconomic studies: utilization of a checklist. AB - OBJECTIVE: To review the fundamental concepts used in clinical economic analysis and establish a simple model to systematically evaluate the quality of pharmacoeconomic studies. DATA SOURCES: A MEDLINE search was used to identify pertinent pharmacoeconomic literature, including reviews. STUDY SELECTION: Selected literature evaluating the methodology of health economics studies was used. CONCLUSIONS: The number of studies presenting a pharmacoeconomic evaluation has increased progressively; however, the quality of the studies has not improved in parallel. The existence of different types of pharmacoeconomic studies does not justify their arbitrary use and the achievement of valid conclusions must be based on sound knowledge of the concepts employed, as well as on use of the most adequate tool in each instance. By evaluating pharmacoeconomic studies systematically, the more common errors (i.e., in planning the study or interpreting the results) can be detected and thus prevented. The checklist we present has 12 sections, each of which includes several subsections. After evaluating the corresponding subsections, each section is labeled as "correct," "acceptable," "doubtful," "incorrect," or "not applicable." From this qualitative evaluation, aspects that have been dealt with correctly and those needing improvement will become apparent. Also, the checklist permits the user to verify whether the results have been correctly obtained and, therefore, whether the conclusions are valid. The use of a checklist for evaluating pharmacoeconomic studies may be useful for researchers, journal editors, and the audience when performing, receiving, reading, or accepting a clinical economic study. PMID- 8219450 TI - Challenge to clinical pharmacy practice in Malaysia. AB - OBJECTIVE: To report on the current status and future trends of clinical pharmacy practice in Malaysia. DATA SOURCES: Published conference reports and journal articles. DATA EXTRACTION: Data on areas related to clinical pharmacy practice in Malaysian hospitals were gleaned from various publications. DATA SYNTHESIS: Malaysia is capable of implementing clinical pharmacy services in hospitals and perhaps also in the community setting. The important factors in clinically oriented pharmacy practice include improvement of the drug-control process, development of physical and human resources, clinical pharmacy skills, and the training of practicing pharmacists. A number of Malaysian pharmacists have already developed a unit-dose drug distribution system, patient counseling, therapeutic drug monitoring, drug information, and total parenteral nutrition services. CONCLUSIONS: The pharmacy profession in Malaysia has many challenges ahead and it is hoped that every practicing pharmacist will be highly committed to future professional needs so that clinical pharmacy practice in Malaysia becomes a reality. PMID- 8219451 TI - Thyroxine-induced partial complex status epilepticus. PMID- 8219452 TI - Trimethoprim/sulfamethoxazole-induced rash, fever, abnormal liver function tests, leukopenia, and thrombocytopenia. PMID- 8219453 TI - Aseptic meningoencephalitis after iopamidol myelography. PMID- 8219454 TI - Lack of vesicant activity of ondansetron. PMID- 8219455 TI - Buzz words and bounties. PMID- 8219456 TI - Comment: angiotension-converting enzyme inhibitor hepatotoxicity: further insights. PMID- 8219458 TI - Early child health in Lahore, Pakistan. A SAREC project for research and research training. 1981-1993. PMID- 8219457 TI - Comment: sorbitol in oral liquids. PMID- 8219459 TI - Early child health in Lahore, Pakistan: X. Mortality. AB - Mortality during the first two years of life among 1476 Pakistani infants born between September 1984 and March 1987 is described according to age, causes of death, area of living, season of the year and sex. The mortality rate (deaths under two years/1000 live births) projected over the whole population of Pakistan was 127 and under one year 114. During the first two years of life, the mortality rate was 133/1000 in the village, 159 in the periurban slum, 107 in the urban slum and 17 in the upper middle class group. In the latter group all deaths had occurred within 72 hours after birth. The overall major causes of death were acute and prolonged diarrhoea (36%), asphyxia neonatorum (13%), respiratory infections (13%), septicaemia (11%) and tetanus (9%). A clear age dependency was noted with 14% of deaths occurring during the first 24 hours of life (asphyxia neonatorum in 86%), and 57% dying within the first 28 days of life. In the later age groups, infections were mainly responsible for 82% of total deaths. Early mortality was therefore extremely high in the poorer areas studied and the cause of death was highly age dependent. Any interventions for reducing mortality must therefore be directed towards better antenatal care and safe delivery and postnatally, towards preventing infections, especially during the first six months of life. PMID- 8219460 TI - Early child health in Lahore, Pakistan: XI. Growth. AB - This work gives growth reference values at birth to 24 months of age for Pakistan based on upper middle class infants. Growth rate reference values are also included and they are given for various interval lengths. The growth was differently affected in infants living in three poorer areas; the stunting incidence at 24 months of age was 63% in periurban slum, 54% in the village and 26% in the urban slum. Less differences could be seen between the areas in weight for length. There was an age dependency in the incidence of reduced growth; a normal length gain was seen at birth to about six months of age, but they were highly reduced at 6 to 18 months of age. The weight gain was to some degree reduced during the first 12 months of life, followed by a catch-up growth period. The seasonal influence was also age dependent; weight was highly affected during the summer at birth to 24 months of age, but not in the winter. The seasonal effect in length was marginal at birth to 6 months, little at 6 to 12 months (although, constant below the normal) and large at 12 to 24 months of age. We did not see any seasonality of growth in the reference group. The incidence of reduced growth reflects the socio-economic differences in one restricted geographic area, i.e., in the city of Lahore, Pakistan. PMID- 8219461 TI - Early child health in Lahore, Pakistan: XII. Milestones. AB - Psychomotor development was assessed in 1476 infants from four different levels of urbanization in and around Lahore, Pakistan. Development was assessed monthly at birth to 24 months of age by using a set of 10 milestones selected from the Denver Developmental Screening Test and the Developmental Screening Inventory. The psychomotor development of children in the upper middle (Um) class was consistent with reference population groups in Europe and North America, hence this group was used as control. There was significant delay in the psychomotor development of infants belonging to the poorer areas compared to the Um class. There was no sex difference in the development of the milestones in any study area, except for girls in the Um class who were earlier for about one month than boys in talking. Infants in the poorer areas were, on average about 3 months, delayed in their walking and fine motor activity (building a tower of 3 cubes) in comparison with the Um class. Observed disturbance in psychomotor development at an early age may affect the abilities and achievements in later life. PMID- 8219462 TI - Early child health in Lahore, Pakistan: XIII. Primary teeth emergence. AB - The aim of this study was to investigate the number of emerged primary teeth at various ages from 6 to 24 months in 1347 longitudinally followed Pakistan infants sampled from four socio-economically different areas in Lahore, Pakistan; from a very poor periurban slum to a privileged upper middle class group. The emergence of the primary teeth was found to be little, or not all related to sex or to the area of living. However, in comparison with studies conducted in other continents, the Indo-Pak subcontinent population lags behind in primary teeth emergence, especially in early life. This genetic difference makes it necessary to create specific standards of primary teeth emergence for this population. PMID- 8219463 TI - Early child health in Lahore, Pakistan: II. Inbreeding. AB - The prevalence of consanguineous marriages was studied in 940 families belonging to four different socio-economic groups in and around Lahore, Pakistan. The births occurring in these families from September 1984 to March 1987 were also investigated for birth defects. The overall prevalence of consanguineous marriages was 46%. The first cousin marriages were most common (67%), followed by the marriages between second cousins, 19%. The prevalence of consanguineous marriages was clearly associated with the socio-economic status of the study groups; 50% of the marriages was related in the periurban slum, 49% in the village, 44% in the urban slum and 31% in the upper middle class. The birth defects were also more prevalent in the poorer areas, being highest in the periurban slum (17.7%) followed by the urban slum (15.6%) and then the village (14.8%) and lowest in the upper middle class (12.3%). Although, the frequency of both consanguinity and birth defects were related with the socio-economic levels of the study groups, there was no association between inbreeding and birth defects. Perhaps, deleterious recessive genes for birth defects have been "bred out", because of continuous inbreeding over generations in this population. There was a significant predilection of major birth defects in boys without clear sex linkage. The conclusion is that the rate of consanguineous marriages was high, especially in the poorer areas, but the relationship between consanguineous marriages and birth defects was little or none. However, other child health indicators may be affected by consanguineous marriages. PMID- 8219464 TI - Early child health in Lahore, Pakistan: III. Maternal and family situation. AB - The family situation for mothers, in three areas differing in degree of urbanization and an upper middle class control group, in Lahore, Pakistan was described. Area differences in socio-economic, family composition, and housing and sanitary conditions were investigated. Data from a longitudinal sample (n = 1476 newborns) were compared with data from a cross-sectional population survey (n = 2998 families). Risk factors for child mortality and morbidity were common in the village and periurban slum area; conditions were somewhat better in the urban slum community. The sample was concluded to be representative of the population in the three areas and also for Pakistan in general. Two indices for cross-study comparisons were proposed, one for socio-economic background and the other for housing standard. The two indices were shown to be related to maternal weight for height at 9 months of pregnancy in the urban slum area; the socio economic level was also functionally related to the weight for height measure in the village. The lower socio-economic and housing standard level, the lower was the mothers' relative weight just before childbirth. The findings were discussed in terms of risk factors for infant mortality, morbidity and psychological development. PMID- 8219465 TI - Early child health in Lahore, Pakistan: I. Study design. AB - In this paper, details are given of a community based follow up study of four areas: a village, a periurban slum, an urban slum and an upper middle class control group living in and around Lahore, Pakistan. The aim was to characterize the determinants of child health in a rapidly urbanizing community. The study was undertaken in two steps. An initial cross-sectional survey collecting socio economic and demographic background information was carried out between March to August 1984. This was followed by a longitudinal study of 1476 infants representing the outcome of the pregnancies registered continuously between September 1984 to March 1987 among the 3242 families in the study. These infants were followed monthly from birth to 3 years of age and thereafter less frequently. In this communication we describe the study design, the study population, the organization and the research methodology used, including the reasons for drop outs from birth to 24 months of age. The internal consistency of the data is also presented. After the initial examination of the newborns within between 0-7 days of birth, the infants were visited monthly for 24 months making a total of 20911 examinations. At 24 months of age 70% of the infants were still in the study, 11% had died before reaching this age, 13% had moved from the area and 6% had refused to participate in the study. The economic, conditions, social structure, and the quality of life were found, not surprisingly, to vary significantly among the four areas. This community-based project provides new, critical and reliable information for local health planners. The study highlights the importance of the development of a useful model for research collaboration between institutions in developed and developing countries. PMID- 8219466 TI - Early child health in Lahore, Pakistan: IV. Child care practices. AB - Child care practices and hygiene measures were studied at 6 months of age in a longitudinally followed cohort of 1476 infants born between September 1984 to March 1987 in four socio-economically different areas in and around Lahore, Pakistan. Although, 76-98% of the mothers looked after their infants during health and 96-98% during a diarrhoeal illness, child care practices and hygiene measures differed significantly between the four areas. During a diarrhoeal episode, the mothers from the upper middle class took timely medical help, fed ample food and Oral Rehydration Salts (ORS) to the sick infants and provided uncontaminated food to them in clean surroundings. The mothers from the village and the periurban slum took their sick child, mostly after the second day of illness, to a doctor, but preferred home remedies. Fourteen percent of the mothers in the village and 6% in the periurban slum did not seek any medical help at all. One-third of the families, from these two areas, fed food to children 12 hours after cooking; the surroundings of the child were dirty with large numbers of flies present throughout the year, though the food was commonly kept covered with a lid. We constructed a simple measure of the surroundings of the child, rated as dirty, medium or clean; it was found to be associated to both parental illiteracy and child growth, but not with housing standard. The main conclusion is that any attempt to improve child-care practices and the hygienic environment for the child, should focus on maternal literacy and simple health messages. PMID- 8219467 TI - Early child health in Lahore, Pakistan: V. Feeding patterns. AB - The feeding practices of children (n = 1476) from birth to 24 months, as determined in a longitudinal study, in Lahore, Pakistan, are presented. Four socioeconomic groups at various levels of urbanization were included; a village, periurban slum, urban slum and an upper middle class. Initiation of breastfeeding was delayed in all the neonates. Sixty-five percent of the periurban slum mothers and 45% of the village mothers had not started breastfeeding at 48 hours after the birth of the infant. Prelacteal feedings, especially of herb water and honey, were the norm. Breastfeeding was highly prevalent. Eighty-seven to 98% of the infants in all the areas were breastfed at one month of age. Exclusive breastfeeding was rare, with 9% at one month, declining rapidly with age and being highly influenced by season. Partial breastfeeding was the most common mode of feeding. Water in addition to human milk was given by 45-73% of the mothers living in the urban slum, village and periurban slum at one month of age. Fresh animal milk and/or commercial formula was already being given at 1 month by 22 64% of the mothers in all areas. Commercial formula was the preferred food in the upper middle class, while in the other three areas it was rare and fresh animal milk was mainly used. More than 50% of the mothers in the village and in the periurban slum gave diluted animal milk even beyond the age of 10-15 months. In the upper middle class 50% of the infants were fed semisolids at the age of four months, while in the village, the periurban and the urban slum at 6 months of age only 10%, 12% and 47% of the infants received semisolids. The results of this study indicate that breastfeeding was highly prevalent in the three poorest areas. However, in all the areas initiation of breastfeeding was delayed and prelacteal feeding was the norm. Exclusive breastfeeding was rare, feeding bottles were used by 82-100% of the mothers to feed supplements and human milk substitutes, in the four areas. PMID- 8219468 TI - Early child health in Lahore, Pakistan: VI. Morbidity. AB - Morbidity patterns were studied according to the age, area of living, sex and season among 1476 monthly followed infants born during 1984-1987 in four socio economically different areas in Lahore, Pakistan. Infections were responsible for 87.0% of the morbidity during the first two years of life. The overall monthly based morbidity was 77.0% between birth and 24 months of age; diarrhoeal diseases 30.3%, upper and lower acute respiratory tract infections (ARI) 22.4%, skin and eye infections 6.7% and skin rash 6.2%. The vaccine-preventable diseases were only 0.5% of the total. Anaemia and rickets were rare (2.0%), but commonly seen among the nutritional deficiencies. Diarrhoea, tetanus, septicaemia, ARI and infections of the skin and eyes were reported more during earlier ages and from the three poorer areas of living. Diarrhoeal diseases, respiratory tract, skin and eye infections, in particular, followed clear seasonal patterns, while scabies prevailed throughout the year. The presence of these many preventable infections and illnesses implies that proper planning of interventions must be forthcoming. PMID- 8219469 TI - Early child health in Lahore, Pakistan: VII. Diarrhoea. AB - This study was carried out to obtain reliable prospective data on the incidence, home management and duration of infantile diarrhoeal disease in a developing and rapidly urbanizing community. Fourteen hundred and seventy six infants from 4 different communities of Lahore, representing different stages of urbanization, were followed prospectively from birth to 2 years of age. Each child had an average of 3.6 episodes of diarrhoea during one year; 4.3 episodes per child per year in the village, 4.4 in the periurban slum, 3.4 in the urban slum and 1.4 in the upper middle (Um) class control group. The maximum incidence of diarrhoeal episodes occurred in children between 9-10 months of age. No sex difference was found. The seasonal variation showed a peak incidence during April-June. Bloody diarrhoea, in 3-5% of the episodes, was predominantly seen in winter months and in older infants. The maximum use of ORS was seen in the Um class (53%). Antibiotics were used in 75% of all diarrhoeal episodes maximally in the Um class, and morphine derivatives in 1% of all cases. The overall incidence of persistent diarrhoea was 14% of all acute cases, being highest in the village (18%), followed by the periurban slum (14%), Um class (10%) and urban slum (8%) with peak incidence occurring in June and July. Our results confirm the magnitude of the problem of diarrhoea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219470 TI - Early child health in Lahore, Pakistan: VIII. Microbiology. AB - The causative agents of acute diarrhoea were investigated in children under the age of five years from 1985-1991 in three socio-economically different areas in Lahore, Pakistan. The aim was to determine the frequencies of the most common enteropathogens in faeces. The total isolation rate was 73.4%; two thirds (53.5%) were of bacterial and one third (19.9%) of viral origin. ETEC-LT (23.4%), Rota virus (19.9%), EPEC (15%) and Campylobacter (12%) were the single most frequent pathogens in all age groups and areas of living. The positivity of Campylobacter increased from 1.6% to 12% after the change of isolation technique. Shigella was isolated significantly (p > 0.001) more in children over than under one year of age. The incidence of bacterial infections was high during all seasons, while in certain years Rota virus was relatively low in the summer compared to the cooler months. The prevalence of ETEC-LT diarrhoea was higher in the periurban slum as compared to the village and the urban slum. The study is the first of its kind in Pakistan, and the results are similar to other comparable studies. It is thus possible to establish a well functioning and reliable microbiological laboratory in developing countries in a setting with restricted trained personnel and material resources. PMID- 8219471 TI - Early child health in Lahore, Pakistan: IX. Perinatal events. AB - In Pakistan there are a number of acute problems related to maternal and infant health in the perinatal period. There is also lack of reliable data needed for the formulation of action strategies. To provide a database 1490 women have been followed from the 5th month of pregnancy in four different areas at various levels of urbanization and socio-economic development. After adjusting for gestational age, the proportion of newborns with weight for length < -2SDS in relation to the Swedish National Standard was 12-31% for boys and 12-25% for girls, the figure being highest in the most deprived area. Preterm birth was infrequent compared with IUGR. The overall prevalence rate of birth defects was 21% out of which 8% were severe defects. The overall perinatal mortality rate was 56/1000 births, with rates of 60, 75, 36 and 33/1000 births for the village, periurban slum, urban slum and the upper middle class. Two thirds of the deaths were related to either a continuation of intrauterine disturbances or severe congenital defects incompatible with life. One third of the deaths were due to infection; mostly diarrhoea, clinical sepsis and ARI. Neonatal mortality was significantly related to birth length (< -2SDS, odds ratio 5.5) and length of gestation (< 37 weeks, odds ratio 5.6) and was to a lesser extent related to weight (< -2SDS, odds ratio 2.0) and weight for length (< -2SDS, odds ratio 1.3). Forty percent of the mothers had weight for height below -2SDS, 23-35% had height < -2SDS. Forty percent of mothers from a subset within the cohort had a hemoglobin < 10 gm/dl and 20% showed signs of pre-eclampsia. This presentation raises the issue of expanding the current Child Survival Programs into the perinatal period as well. PMID- 8219472 TI - 15th International Symposium on Growth and Growth Disorders. Florence, Italy, 2-3 April 1993. Proceedings. PMID- 8219473 TI - Growth hormone (GH) receptors, GH binding protein and GH: an autoregulatory system? PMID- 8219474 TI - Genetic heterogeneity in Laron syndrome. PMID- 8219475 TI - Endocrine regulation of longitudinal bone growth. PMID- 8219476 TI - Studies on growth plate chondrocytes in situ: cell proliferation and differentiation. AB - In man, attaining full longitudinal growth and skeletal maturity may go towards preventing later problems, such as osteoporosis. In farmed species, it is becoming increasingly apparent that muscle growth or the calcium demands for reproduction have outstripped the ability of the skeleton to provide both support and sufficient calcium. Thus, understanding the mechanisms that control longitudinal growth is of vital importance. Methods for studying chondrocyte proliferation and differentiation increasingly rely on the use of isolated cells, but these do not reproduce in vivo conditions. It is therefore necessary to be able to assess chondrocyte function in situ in order to understand fully the actions of possible growth promoters and therapeutic agents. The control of chondrocyte proliferation seems to be heavily dependent on GH, which probably acts directly on the resting and proliferating chondrocytes (Fig. 3). In the former, it seems to regulate the commitment of prechondrocytes to the proliferative state, but the mechanisms whereby it achieves this are unclear. What is also unclear is the proportion of growth that is GH dependent and how much, if at all, the control of IGF-I production by nutritional and other factors contributes to longitudinal growth. The in situ biochemical approach has provided strong evidence that both TGF-beta and the c-myc proto-oncogene are involved in chondrocyte differentiation and may be early markers of this process (Fig. 3). Indirect evidence exists to support a role for c-myc expression in chondrocyte differentiation, as TGF-beta has been reported to have its mechanisms of action modulated by c-myc expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219477 TI - Identification of growth hormone receptors on human growth plate chondrocytes. PMID- 8219479 TI - Cell kinetics and the control of bone growth. PMID- 8219478 TI - In vitro effects of growth hormone and other hormones on chondrocytes and osteoblast-like cells. AB - The influence of growth hormone (GH), insulin-like growth factor I (IGF-I), parathyroid hormone(1-34) (PTH(1-34)), 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and 17 beta-oestradiol on proliferation and on production of cytokines, such as interleukin-1 beta (IL-1 beta), IL-6, IL-8 and transforming growth factor-beta (TGF-beta), was studied in chondrocytes obtained from the growing cartilage of the iliac crest and in the osteoblast-like cell clone SaOS 2. GH and IGF-I were mitogenic for chondrocytes and SaOS-2 cells, as indicated by the dose-related increase in uptake of [3H]thymidine. PTH(1-34) was also mitogenic, while 1,25(OH)2D3 inhibited the proliferation of both chondrocytes and SaOS-2 cells in a dose-dependent manner. 17 beta-oestradiol was stimulatory in SaOS-2 cells, but gave a biphasic pattern in chondrocytes; it was stimulatory at low concentrations (0.1 nmol/l) and inhibitory at supraphysiological doses (10 nmol/l). Using the cDNA polymerase chain reaction, specific mRNAs for IL-1 beta, IL-6, IL-8 and TGF-beta were found in chondrocytes, while SaOS-2 cells had a positive signal only for TGF-beta. Specific enzyme immunoassays revealed detectable levels of IL-1 beta, IL-6 and IL-8 only in chondrocytes. IL-6 was increased by GH and IGF-I, and lowered by 1,25(OH)2D3 and supraphysiological doses of 17 beta-oestradiol, while PTH(1-34) had no effects. IL-8 was not influenced by GH or IGF-I, was slightly but not significantly increased by PTH(1 34) and was reduced by 1,25(OH)2D3 and 17 beta-oestradiol at supraphysiological doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219480 TI - Demography, auxology and response to recombinant human growth hormone treatment in girls with Turner's syndrome in the Kabi Pharmacia International Growth Study. International Board of the Kabi Pharmacia International Growth Study. AB - Demographic and auxological data were analysed from 818 girls with Turner's syndrome treated with recombinant human growth hormone (GH) and entered into the Kabi Pharmacia International Growth Study. Size at birth was low and correlated with the heights of both parents. The median age at start of GH treatment was 11.4 years and the parents had a median height SDS of -2.9. Height SDS at the start of treatment correlated with parental heights. Height velocities conformed to Turner-specific standards. The weight-for-height index increased sharply above 9 years of age. The frequency of spontaneous appearance of Tanner breast stage 2 was high (34.1% of girls > 10 years of age). Bone age (Greulich and Pyle) data were described by the equation: bone age = 1.61(chronological age) - 0.04(chronological age)2 - 3.61. This equation was used to correct adult height predictions. The median initial dose of GH was 0.8 IU/kg/week and was maintained during the first 3 years of treatment. The median frequency of injections was six/week. Height velocity increased from 4.1 to 6.8 cm/year in the first year, and height velocity SDS for chronological age remained positive for 4 years. The height prediction corrected for bone age increased over the first 2 years only. Differences in demography and auxology were described according to karyotype and country of origin. A greater height velocity SDS was observed at higher GH doses and when oxandrolone was used concomitantly. PMID- 8219481 TI - Characteristics of children with idiopathic short stature in the Kabi Pharmacia International Growth Study, and their response to growth hormone treatment. International Board of the Kabi Pharmacia International Growth Study. AB - The auxological characteristics and the response to growth hormone (GH) treatment of children with idiopathic short stature were studied, using the database of the Kabi Pharmacia International Growth Study. Pretreatment data from a total of 271 children were analysed. The children were selected for a birth weight above -2 SDS. The correlation coefficient of birth weight SDS and birth length SDS was 0.51, compared with 0.72 for the reference population. Median length at birth was -0.6 SDS, which fell to -2.5 SDS by 3 years of age. Thereafter, there was no further loss in height SDS. The response to GH treatment was studied in 222 of these prepubertal children who were given six or seven injections/week over a 3 year period. During this time, the median height SDS increased from -2.5 to -1.5, with those children receiving more than 0.65 IU/kg/week having a greater gain in height SDS than those on 0.5 IU/kg/week or less. The degree of bone age delay did not appear to influence the response to GH therapy. PMID- 8219482 TI - Auxology and response to growth hormone treatment of patients with intrauterine growth retardation or Silver-Russell syndrome: analysis of data from the Kabi Pharmacia International Growth Study. International Board of the Kabi Pharmacia International Growth Study. AB - Using the database from the Kabi Pharmacia International Growth Study, 105 patients with intrauterine growth retardation (IUGR) (82 males, 23 females) and 45 with Silver-Russell syndrome (SRS) (32 males, 13 females) with persistent postnatal growth failure were studied. Patients with IUGR had a birth length and birth weight more than 2 SD below the mean for gestational age. Their height deficit at the start of GH treatment was -3.0 SDS at a median chronological age of 8.7 years and a median bone age of 7.0 years. Mean paternal and maternal heights were 166 and 153 cm, respectively. The median dose of GH was 0.5 IU/kg/week, given at a median frequency of five injections/week. The median height SDS for chronological age after 1, 2 and 3 years of GH treatment were 2.5, -2.1 and -1.9, respectively. In the 45 patients with SRS, median chronological age and median bone age at the start of treatment were 6.7 and 3.2 years, respectively, and mean paternal and maternal heights were 167.5 and 160 cm, respectively. The median dose of GH was 0.7 IU/kg/week, given at a median frequency of six injections/week. The median height SDS for chronological age at the start of treatment and after 1, 2 and 3 years were -3.5, -2.9, -2.8 and -2.2, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219483 TI - Prediction of the growth response in children with various growth disorders treated with growth hormone: analyses of data from the Kabi Pharmacia International Growth Study. International Board of the Kabi Pharmacia International Growth Study. AB - Analyses to predict the growth response to recombinant human growth hormone (GH) in prepubertal children during the first year of treatment were performed on data from 472 patients with idiopathic GH deficiency (IGHD), 202 children with Turner's syndrome, 327 children with idiopathic short stature (ISS) and 135 children with intrauterine growth retardation (IUGR). In IGHD, 56% of the variability of the response could be predicted from a model based on six variables. These variables could be ranked in order of importance as follows: target height SDS minus height SDS, chronological age, frequency of GH injections, dose of GH, weight-for-height index, and birth weight SDS. When the model for IGHD was applied to Turner's syndrome, ISS and IUGR, there was a high degree of similarity between the predicted and achieved growth response in ISS and IUGR. However, an uneven distribution within the plot of Studentized residuals in ISS and IUGR suggested heterogeneity within these populations. Prediction of growth in Turner's syndrome was greatly exaggerated by the model for IGHD, suggesting a different pathogenesis as the basis of the growth disorder. Specific prediction models were therefore developed for Turner's syndrome, ISS and IUGR. In all three disorders, the dose of GH was found to be the most important predictor, suggesting that, in contrast to IGHD, first-year growth is governed less by the difference between height and the presumed genetically determined target height. Again, in contrast to IGHD, this suggests that catch-up phenomena are not involved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219484 TI - Pharmacokinetics of recombinant human insulin-like growth factor I given subcutaneously to healthy volunteers and to patients with growth hormone receptor deficiency. AB - The pharmacokinetics of recombinant human insulin-like growth factor I (rhIGF-I) were studied in healthy volunteers and in patients with growth hormone receptor deficiency (GHRD; Laron syndrome). Following single subcutaneous injections of rhIGF-I, 40 and 80 micrograms/kg, to healthy volunteers, the peptide was absorbed slowly, with a maximum concentration reached after about 7 hours. Following daily multiple subcutaneous injections of rhIGF-I, 40 micrograms/kg, trough concentrations of IGF-I were increased by 277 +/- 50 micrograms/l (mean +/- SD) from baseline. IGF-I was thus characterized as a low-clearance peptide, with a clearance and half-life estimated at about 0.20 ml/minute/kg and 20 hours, respectively, in healthy volunteers. The volume of distribution was low, about 0.20-0.36 litres/kg, the bioavailability of subcutaneously administered rhIGF-I was 100%, and the rate of production of IGF-I was estimated to be about 50 micrograms/kg/day (3.5 mg/day). Patients with GHRD had low baseline IGF-I concentrations (30-50 micrograms/l) and a much more rapid turnover of IGF-I compared with that in healthy volunteers. The clearance and half-life of IGF-I were estimated to be about 0.60 ml/minute/kg and 6 hours, respectively. The volume of distribution was about the same as in healthy subjects. Due to the rapid turnover of IGF-I, trough IGF-I concentrations were increased to just above baseline during subcutaneous injections of 40 micrograms/kg once daily for 7 days. The maximum increase in IGF-I levels was 111 +/- 12 micrograms/l and 150 +/ 3 micrograms/l following daily subcutaneous injections of 40 x 1 and 40 x 2 micrograms/kg for 7 days, respectively. PMID- 8219485 TI - The intrauterine origins of cardiovascular disease. PMID- 8219486 TI - Continuing the search for bacterial urovirulence factors. AB - Bacteria that commonly cause infections of the normal urinary tract (eg Escherichia coli, Proteus mirabilis and Staphylococcus saprophyticus) do so because they possess specific urovirulence factors. Adhesions of various types (often fimbriae) seem to be the most important of these. In E. coli several other factors have been recognized, and sub-sets of defined uropathogenic clones exist. On the other hand, urovirulence determinants are less easy to distinguish in species such as S. epidermidis and Klebsiella pneumoniae, that rarely cause such infections, or are pathogenic only in the presence of some abnormality or deficiency in host defences. PMID- 8219487 TI - Nonculturable but still viable and potentially pathogenic. PMID- 8219488 TI - Metabolism of phosphate-limited cultures of Streptomyces. IV. Protein phosphorylation of antibiotics-producing cultures. AB - It has been demonstrated that in the cellular proteins of Streptomyces hygroscopicus JA 6599 and Streptomyces noursei JA 3890 b, the producers of the antibiotics turimycin and nourseothricin, respectively, phosphorylated proteins are present. Numbers and concentrations of phosphorylated proteins decreased during the idiophase as characterized by phosphate limitation, antibiotic biosynthesis and phosphatase formation. Phosphoamino acids of serine, threonine and tyrosine were found in the hydrolysates of proteins. Protein tyrosyl kinase was demonstrated in the cellular extracts. The results supports the hypothesis that protein phosphorylation possesses a function in the regulation of growth and secondary product formation. PMID- 8219489 TI - Isolation of a new serovar of the genus Leptonema in the family Leptospiraceae. AB - A leptospira-like spirochete was isolated from a lymphocyte culture from a HIV-I and HTLV-I/II-positive patient. On the basis of serological, biological and morphological characteristics of the cells of the isolated strain (strain Lisboa), we conclude that it is a member of the genus Leptonema. PMID- 8219490 TI - Enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against Salmonella enteritidis in chicken blood or egg yolk. AB - Tracing of flock infection remains one of the most serious unsolved problems of controlling salmonellosis in poultry. In order to overcome this problem, a serological test kit for the detection of antibody to Salmonella enteritidis (1, 9, 12:[f], g, m, [p]:[1, 7]) in chicken flocks was developed. In this study, samples of antisera and the yolk of eggs from different chicken flocks were tested with the ELISA kit, and the resulting flock profiles were compared. The test system clearly allowed a differentiation between flocks which were positive and flocks which were negative for S. enteritidis. Sera from stocks infected with S. typhimurium (1, 4, (5), 12:i:1, 2) or S. heidelberg (1, 4, (5), 12:r, 1, 2) were also analysed in order to determine the relative cross-reactivity in the test. No false-positive results could be shown in the case of S. heidelberg; cross-reactions with antibodies against S. typhimurium were found in 2.5% to 10% of the samples from a particular flock. The test kit could also be used for the analysis of egg yolk samples without time-consuming purification procedures. Specific antibodies were detected in high dilutions of positive egg yolks, thus enabling a rapid screening for S. enteritidis-positive chicken flocks. PMID- 8219491 TI - Monoclonal antibodies with in vitro borreliacidal activities define the outer surface proteins A and B of Borrelia burgdorferi. AB - Thirteen monoclonal antibodies (mAb) were produced against Borrelia burgdorferi strains B31 and PKa. Five mAb recognized the outer surface protein OspA (relative molecular mass (M(r)) 31,000) and four OspB with an M(r) of 34,000. Two of these mAb were directed against flagellin with an M(r) of 41,000, and the remaining two against the antigens of B. burgdorferi with M(r) values of 19,000 and 17,000. Immunoblot and immunofluorescence studies with these mAb on five isolates of B. burgdorferi revealed differences in the individual antigenic epitopes of OspA and OspB. OspA and OspB specific mAb showed a borreliacidal activity in vitro. These antibodies were additionally reactive in haemagglutination and immunofluorescence assays. Enzymatic digestion investigations on intact borreliae suggest that the antigenic determinants of mAb with borreliacidal activity are located in the peptide chain of OspA and OspB. PMID- 8219492 TI - Antibiogram typing of methicillin-resistant Staphylococcus aureus: a comparison with phage typing, biotyping and API Staph. AB - 68 strains of methicillin- and gentamicin-resistant Staphylococcus aureus (MRSA) have been characterized by four different methods. First, by their production of lecithinase, lipase, pigment and sheep haemolysin. Second, by API Staph code. Third, by their sensitivity to 9 antibiotics. Fourth, by phage typing using the International Set and Supplementary phages. The third method was the most discriminatory. The combination of the first three techniques provides a highly effective, cheap and simple system to type MRSA. 80 separate MRSA strains from 26 countries were found to belong to a wide variety of phage types. Most were of group III. The most commonly found types were 85 (6 strains), 84 (4 strains) and 47 (3 strains). PMID- 8219493 TI - Detection of bacterial nitrate reductase activity by the use of a powdered reagent and rapid swab methods as compared to the conventional test. AB - A rapid swab method using either a dry or moist swab soaked with potassium nitrate/benzalkonium chloride solution, and a method employing a single powdered reagent were assessed as possible alternatives to the conventional test for the detection of bacterial nitrate reductase activity. Results obtained by the use of the powdered reagent agreed 100% with those obtained by the conventional method. The moist swab method had a sensitivity and predictive value of the negative test of 80% and 73%, respectively. The dry swab method was least sensitive (72%) and had the lowest predictive value of the negative test (66%). The use of the single powdered reagent, which has a long shelf life, is a reliable alternative to the use of conventional reagents A and B. Results obtained by the rapid swab methods were inferior to those obtained by the conventional method. PMID- 8219494 TI - The salting-out test to identify virulent Yersinia pseudotuberculosis. AB - A total of 54 strains including 8 serotypes of Yersinia pseudotuberculosis were examined to find out about their cell surface hydrophobicity and virulence plasmid-associated properties. All the strains which aggregated in 0.9% saline expressed the properties of calcium-dependent growth and autoagglutination. However, the hydrophilic strains did not possess virulence plasmid-associated properties. The above results suggest that the salting-out test with 0.9% saline could be an effective measure to differentiate the virulence plasmid-carrying strains of Y. pseudotuberculosis from those of plasmidless virulence. PMID- 8219495 TI - Prevalence of antibodies to Borrelia burgdorferi flagellin in Styrian blood donors. AB - Lyme borreliosis and tick-borne encephalitis (TBE) are the most common diseases in Austria caused by tick bites. TBE endemic areas are well defined. It seemed to be of interest to compare prevalence data of antibodies against Borrelia burgdorferi (B.b.) to TBE endemic and non endemic areas. Blood samples (n = 1162) were obtained from healthy blood donors in combination with a standardized questionnaire during 21 excursions to 7 selected regions of Styria, Austria. Serum samples were screened for IgG antibodies against B.b. by a commercial flagellum ELISA. None of the tested persons showed symptoms of active Lyme borreliosis. A higher prevalence of antibodies against B.b. could be found in TBE endemic areas (7.7%) compared to TBE nonendemic areas (3.8%). There was a significant increase in positive antibodies against B.b. with age, exposure and number of tick bites remembered by test persons. The antibody prevalence to B.b. flagellin antigen is significantly higher in TBE endemic areas than in non endemic comparative regions. PMID- 8219497 TI - Hemagglutination by Pasteurellaceae isolated from rodents. AB - Pasteurellaceae notably P. pneumotropica, have been associated with severe outbreaks of respiratory disease in several species of rodents. Host-specific parasitism of Pasteurellaceae in rodents has hardly been studied. Since host tropism in many bacteria involves adhesive mechanisms, we examined the hemagglutinating (HA) properties of 44 isolates from different rodent species (mouse (15) rat (8), hamster (9), gerbil (10) and Mastomys (2)). Only 13 mouse isolates and the 2 Mastomys isolates hemagglutinated human (type O Rh+) and canine red blood cells (RBCs). No HA was found using RBCs from 10 other animal species. HA was not inhibited by simple sugars and glycoconjugates, but was completely inhibited by heating of bacterial cells for 10 min at 80 or 100 degrees C, partially inhibited by glutaraldehyde and inhibited in a dose dependent mode by NaIO4, suggesting the involvement of bacterial polysaccharide structures in the HA process. Enrichment procedures did not reveal the presence of HA- subpopulations in HA+ isolates or the presence of HA+ subpopulations in HA isolates. Electron microscopy revealed the presence of fimbriae both in HA+ and HA- isolates. A regularly structured (RS) layer was detected on cells of part of the HA+ isolates only. Our results suggest that Pasteurellaceae of mice and Mastomys may be related and differ from isolates isolated from other rodent species. PMID- 8219496 TI - Immunobiology of Acinetobacter baumannii and genospecies 3. AB - Five representative, taxonomically and serologically defined clinical isolates of Acinetobacter baumannii and genospecies 3, and A. baumannii strain ATCC 19606 were examined for immunogenicity in rabbits following experimental bacteremia. All rabbits seroconverted as determined with the aid of the tube O-agglutination, indirect hemagglutination, and enzyme-linked immunosorbent assay (ELISA) procedures. Immunoblots detected over twenty immunogenic, proteinase-K-degradable polypeptide antigens in trichloroacetic acid extracts, outer membrane protein fractions, and mechanically disrupted (type MM2 mixer drill) cell preparations. Sodium periodate-susceptible phenol-water and phenol-chloroform-light petroleum lipopolysaccharide (LPS) extracts proved to be immunogenic for the rabbits as well. Convalescent sera from two patients with documented bacteremia due to genospecies 3, serovar 4, likewise revealed numerous anti-polypeptide and anti LPS antibodies comprising the immunoglobulin G (IgG) and the IgM class. PMID- 8219498 TI - Detection of feline immunodeficiency virus proviral DNA in feline peripheral blood mononuclear cells by the nested two-step polymerase chain reaction. AB - The polymerase chain reaction (PCR) was applied to detect feline immunodeficiency virus (FIV) proviral DNAs in primary peripheral blood mononuclear cells (PBMC). Suitable conditions for PCR amplification were examined to obtain highly sensitive and specific results by simple staining in agarose gel. Specific amplification of FIV proviral DNA in PBMC DNA of FIV-infected cats was achieved by a nested two-step PCR that amplified the DNA first with outer primers and then with inner primers nested within the first primers. PCR amplification using different primers indicated that those based on the gag sequence of the FIV/TM2 strain isolated in Japan were suitable for the detection of FIV genomes in naturally infected Japanese pet cats. By the nested two-step PCR with mixed gag primers of TM2 and Petaluma, isolated in the USA, we could detect FIV genomes in all 11 primary PBMC samples from FIV-seropositive cats tested. The PCR protocol developed here is sensitive and specific for molecular detection of FIV infection in cats. PMID- 8219499 TI - Erythrogenic toxin type A (ETA): epidemiological analysis of gene distribution and protein formation in clinical Streptococcus pyogenes strains causing scarlet fever and the streptococcal toxic shock-like syndrome (TSLS). AB - Erythrogenic toxin type A (ETA) is assumed to play a causative role in both scarlet fever and the streptococcal toxic shock-like syndrome (TSLS). For a molecular epidemiological analysis of the gene of erythrogenic toxin type A (speA) we used altogether 497 clinical isolates of Streptococcus pyogenes belonging to three groups: a) isolates from patients with scarlet fever, b) isolates from cases with TSLS, c) isolates from patients with other streptococcal infections (like otitis media, tonsillitis, impetigo) (general group). We found that less than 50% of the scarlet fever-associated strains possessed the speA gene as compared to 25% of the general group. Only 5 to 30% of these strains secreted the toxin under experimental conditions in very low quantities. Among strains isolated from TSLS, 67% appeared to contain the speA gene. The amount of ETA secreted into the medium was also extremely low. Southern hybridization patterns proved to be the same with an speA-specific probe in all three groups of streptococcal isolates (HaeIII, HindIII). Increased occurrence of the speA gene among scarlet fever and TSLS-associated strains does not seem to be sufficient to support the hypothesis that ETA may have a causative role in both diseases since a considerable number of strains in these groups did not possess the speA gene. PMID- 8219500 TI - Adherence of Actinomyces pyogenes to HeLa cells mediated by hydrophobic surface proteins. AB - Determination of cell-surface hydrophobicity of Actinomyces pyogenes by hydrophobic interaction chromatography on phenyl-Sepharose revealed that all 42 cultures examined were strongly hydrophobic. The hydrophobic surface proteins were solubilized by mutanolysin treatment of the bacteria and isolated by hydrophobic interaction chromatography. In SDS-PAGE, they appeared with numerous protein bands and blocked the adhesion of whole bacterial cells to the gel matrix. The A. pyogenes cultures attached to HeLa cells in varying degrees. This attachment of A. pyogenes was greatly reduced in the presence of isolated hydrophobic proteins and in the presence of specific antibodies produced against hydrophobic surface proteins. The results of the present study demonstrate that hydrophobic surface proteins promote the capacity of A. pyogenes to adhere to HeLa cells. PMID- 8219501 TI - Bacteriophages induced by ciprofloxacin in a Borrelia burgdorferi skin isolate. AB - Two types of tailed bacteriophages were detected by electron microscopy in a Borrelia burgdorferi strain which had been isolated from infected human skin and exposed to the gyrase inhibitor ciprofloxacin. One of these phages displayed an isometric 30 nm head, a neck and a contractile tail 50-64 nm in length with a baseplate, according to an A-1 morphology. The other phage showing a B-1 morphology had a 30 nm isometric head as well and a long non-contractile straight tail 115-130 nm in length without neck and baseplate. Both types of phages could be found together within one plasmolysed spirochetal cell. We conclude that we are dealing with a lysogenic strain of Borrelia burgdorferi carrying at least two different prophages inducible by ciprofloxacin. PMID- 8219502 TI - Cellular fatty acid methyl ester profiles as a tool in the differentiation of members of the genus Mycobacterium. AB - The cellular fatty acid profiles of 84 strains belonging to 53 different species of the genus Mycobacterium were determined by gas liquid chromatography-mass spectrometry (GCMS). Two main types and four subtypes of fatty acid profiles were recognizable. The first main type is the G type, nominally referring to M. gordonae, members of which lack tuberculostearic acid or other 10-methyl branched chain fatty acids, but contain normal saturated and unsaturated fatty acids. This type is further subdivided into the G alpha subtype that is characterized by 2 methyl tetradecanoic acid (2-Me-C14:0) as the only 2-methyl branched fatty acid. Strains belonging to the second main type, the T type, nominally referring to tuberculosis, contain tuberculostearic acid and other 10-methyl branched acids in addition to the normal saturated and unsaturated ones. This type has been further subdivided into three subtypes: the T alpha subtype that does not contain any 2 methyl branched fatty acids; the T beta subtype that contains both 2-methyl tetradecanoic (2-Me-C14:0) and 2,4-dimethyl tetradecanoic (2,4-DMe-C14:0) acids as 2-methyl branched fatty acids; the T gamma subtype which contains 2-methyl dodecanoic (2-Me-C12:0), 2,4-dimethyl dodecanoic (2,4-DMe-C12:0) and 2,4-dimethyl tetradecanoic (2,4-DMe-C14:0) acids as 2-methyl branched-chain acids. Fatty acid analysis showed a great homogeneity within the genus and the profiles produced were not very helpful in distinguishing between members of the genus Mycobacterium except for the identification of M. gordonae, M. kansasii, and M. gastri. PMID- 8219503 TI - Glycoprotein patterns in Borrelia spp. AB - The presence of glycoproteins in several Borrelia species was investigated by the digoxigenin labelling technique. The outer surface proteins A and B of seven isolates of the Lyme disease spirochete B. burgdorferi showed to be major glycosylated proteins. Few minor polypeptides with variable molecular masses were also present, at variance, in B. burgdorferi strains. Minor glycosylated proteins with varying molecular masses have been detected in the relapsing fever borreliae B. hermsii, B. turicatae and B. parkeri. B. turicatae showed also a major glycosylated protein with a molecular mass of approximately 40 kDa. Animal pathogenic borreliae B. anserina and B. coriaceae presented only minor glycosylated proteins with variable molecular masses. PMID- 8219504 TI - A comparison of the efficiency of Rappaport-Vassiliadis, tetrathionate and selenite broths with and without pre-enrichment for the isolation of Salmonella in animal waste biogas plants. AB - A total of 481 samples of biomass from biogas plants treating slurry and other types of animal waste were examined for the presence of salmonellae by means of five different isolation methods. In 131 samples, Salmonella was isolated by means of one or more methods. A statistical evaluation of the isolation frequencies showed that Rappaport-Vassiliadis broth was significantly better than selenite broth with and without pre-enrichment and tetrathionate broth with pre enrichment, whereas tetrathionate broth without pre-enrichment was significantly poorer than the other four methods. For each of the thirty different Salmonella serotypes, the isolation frequencies for the five methods are presented. Remarkably, Rappaport-Vassiliadis broth had very high isolation frequencies and tetrathionate broth with and without pre-enrichment had very low isolation frequencies for Salmonella typhimurium as well as Salmonella dublin. PMID- 8219505 TI - Selective pre-enrichment of Salmonella from eggs by siderophore supplements. AB - Salmonella can overcome the iron limitation of iron-limited nutrient media and albumen by utilizing the siderophores ferrioxamine E and G und grow. 14 out of 18 food-poisoning Salmonella strains of different serotypes stored in hen's egg albumen (approx. 2 organisms/ml) could be detected after 6 h of pre-enrichment with buffered peptone water supplemented with ferrioxamine G (1 microgram/ml) on selective nutrient media. In contrast, only 4 of these Salmonella strains could be reisolated without supplementation. E. coli strains cannot be supplied with iron by ferrioxamines E and G. Therefore, Salmonella enteritidis phage type 4/6 could be isolated in great numbers from mixed cultures with E. coli kept in albumen. Buffered peptone water supplemented with ferrioxamine G also permitted a successful reisolation of Salmonella enteritidis from artificially contaminated eggs. Ferrioxamines E and G function as selective growth factors to enhance sensitivity in the isolation of Salmonella in other nutrient media, too. PMID- 8219506 TI - Thin-layer chromatographic analysis of glycolipids and mycolic acids from Mycobacterium farcinogenes, Mycobacterium senegalense and related taxa. AB - Seventy-nine representative strains of Mycobacterium farcinogenes, Mycobacterium fortuitum, Mycobacterium peregrinum and Mycobacterium senegalense were analysed by thin-layer chromatography for diagnostic glycolipid and mycolic acid patterns. On the basis of glycolipid patterns the 16 M. senegalense strains were assigned to four groups (I, II, III and IV); one strain received as M. farcinogenes had glycolipids that corresponded to those given by the M. senegalense group III strain. Representatives of M. fortuitum produced alkalilabile glycolipids whereas the M. peregrinum strains produced alkali-stable glycopeptidolipids related to those of M. senegalense group I. Members of M. senegalense groups I, III and IV and the M. farcinogenes strains gave the characteristic pattern consisting of alpha- and epoxymycolates on thin-layer chromatographic analysis of the products of alkaline hydrolysis with 5% aqueous tetrabutylammonium hydroxide. Extraction of mycolates from the same strains using acid methanolysis revealed alpha mycolates and characteristic more polar long-chain components originating from epoxymycolates. In contrast, the M. senegalense group II strains contained an additional more polar omega-1 methoxymycolate that was detected from both acid and alkaline hydrolysates; this spot was also seen in some M. fortuitum and M. peregrinum strains. Preliminary investigations, using a combination of thin-layer chromatography and immunostaining, showed that glycopeptidolipids from M. peregrinum and M. senegalense group I strains were antigenic, a cross-reaction between members of these taxa was shown. In contrast, no reaction was detected between glycopeptidolipids extracted from M. peregrinum and M. senegalense group I strains with antisera from either M. farcinogenes or M. fortuitum. PMID- 8219507 TI - Plasmid profiles and antimicrobial susceptibility of Campylobacter jejuni isolated from Israeli children with diarrhea. AB - Thirty Campylobacter jejuni (C. jejuni) strains isolated from stools of Israeli children with enteritis were tested for sensitivity to eight antimicrobial agents (MIC) and the presence of plasmids. It was found that all the isolates were sensitive to ciprofloxacin, ofloxacin, furazolidone and erythromycin. Of the 30 strains tested, 21 (70%) were found to be tetracycline-resistant, a relatively high resistance rate as compared with data from other countries and previous reports from Israel. Plasmids were detected in 17 out of 30 C. jejuni isolates (55.6%). A total of nine different plasmid profiles could be distinguished; six profiles were represented by one strain each. Of the 21 tetracycline-resistant strains, plasmids were found in 17 isolates (80%) carrying from 1-2 to 5 plasmids of various sizes. No plasmids were found in tetracycline-sensitive strains, with the exception of one isolate which contained a 24.4 MDa plasmid and was co trimoxazole-resistant. Our studies indicate a relatively high percentage of tetracycline-resistant C. jejuni isolates in the Tel Aviv area. In 80% of these strains, various plasmid profiles were detected. PMID- 8219508 TI - Antimicrobial susceptibility testing of Actinomyces pyogenes: comparison of disk diffusion test and Api ATB Strep system with the agar dilution method. AB - The use of the disk diffusion and the Api ATB Strep system or a related technique for a few antibiotics was compared with the agar dilution method for antimicrobial susceptibility testing of 103 clinical isolates of Actinomyces pyogenes. There was complete agreement between disk diffusion and MIC in 98.8%, with minor errors, in 0.7% and with very large errors, in 0.5% of cases. The common criteria for the interpretation of zones could be kept for penicillin G, amoxicillin, methicillin, cephalothin, erythromycin, lincomycin, pristinamycin, vancomycin, rifampin, streptomycin, kanamycin, gentamicin and chloramphenicol. The proposed breakpoints for a tetracycline 30 IU disk were > or = 22 mm for susceptibility and < 22 mm for resistance. There was complete agreement between the ATB strip system and MIC in 98.3% of cases, with minor errors in 0.9% and with very large errors, in 0.8% of cases. All the dissimilarities were due to streptomycin and tetracycline and results could not be reported for these 2 antibiotics when using this system. Wells with kanamycin and gentamicin at low concentrations as well as chloramphenicol should be included by the manufacturer. PMID- 8219509 TI - In vitro susceptibility of Pasteurella multocida subspecies multocida strains isolated from swine to 42 antimicrobial agents. AB - The minimal inhibitory concentrations (MICs) of 42 antimicrobial agents were determined against 59 strains of Pasteurella multocida subspecies multocida, all isolated from swine lungs with lesions indicative of pneumonia. Penicillins (except cloxacillin), aminoglycosides, tetracyclines, erythromycin, josamycin, thiamphenicol, colistin, rifampin and mupirocin showed good activities, with ranging resistance between 0 and 6.8%. Higher resistance was observed for spiramycin and fosfomycin. Tylosin, vancomycin, metronidazole, dapsone and tiamulin, to which strains showed high rates of resistance, were ineffective. Cephalosporins (especially the third-generation cephalosporins) and quinolones (especially the fluorinated quinolones) were the most effective antimicrobial agents against P. multocida subsp. multocida strains and they might be of value for in vivo use. PMID- 8219510 TI - Distribution of capsular types 1 to 28 and further characteristics of Streptococcus suis isolates from various European countries. AB - Most of the 150 Streptococcus suis isolates from pigs and ruminants used in this study grew under aerobic conditions and were alpha-hemolytic on sheep blood agar. Part of the cultures required an increased CO2 concentration. These cultures, representing the CO2- dependent ecovar of S. suis, were mainly beta-hemolytic on sheep and horse blood agar and gave a synergistic hemolytic reaction with staphylococcal beta-lysin. Similar to S. suis reference cultures, the routine isolates showed typical biochemical properties of this species. Few cultures, mostly those from ruminants, could be classified as the sorbitol and mannitol positive ecovar. Formamide extracts of 81% of the cultures reacted with group D specific antisera. Serotyping of the S. suis isolates revealed mainly capsular types 2, 1/2, 1, 5, 11, 13, 23, 3 and 15. The determination of antibiotic susceptibility revealed a high number of cultures to be resistant to clindamycin, erythromycin, kanamycin, neomycin, streptomycin and tetracycline. Cultural, biochemical and serological properties together with antibiotic resistance patterns could be used to characterize individual isolates of S. suis. This could be of importance in epidemiological studies. PMID- 8219511 TI - The woodmouse (Apodemus sylvaticus) as a reservoir of tick-transmitted spirochetes (Borrelia burgdorferi) in The Netherlands. AB - In three widely separated locations in the Netherlands, woodmice (Apodemus sylvaticus) were trapped, examined for ticks and subjected to xenodiagnosis for the detection of tick-transmitted spirochetes (Borrelia burgdorferi). During the spring and summer, an average of 2.4 Ixodes larvae/mouse (n = 170) was observed, but the true numbers were probably greater. The numbers of nymphs could be determined more accurately and amounted to 0.46 nymphs/mouse. The percentage of mice that were infected with tick-transmitted spirochetes was 47% (n = 45), 29% (n = 58) and 0% (n = 64) for the three locations respectively. The absence of spirochete-infected mice in location 3 is puzzling because spirochete-infected I. ricinus nymphs were collected (infection rate up to 11%) in the same location during the subsequent spring. Sexually active mice were more frequently infected with spirochetes than juveniles and non-sexually active ones. On location 1, the island of Texel, a sample of mice was also caught during the subsequent winter and subjected to xenodiagnosis. The results indicate that B. burgdorferi survives the winter in the vector tick rather than in the reservoir rodents. PMID- 8219512 TI - Comparison of Borrelia burgdorferi ultrasonicate and whole B, burgdorferi cells as a stimulus for T-cell proliferation and GM-CSF secretion in vitro. AB - Peripheral blood mononuclear cells (PBMC) from five patients with confirmed Lyme borreliosis (LB) and from seven seronegative healthy subjects were incubated with ultrasonicated sterile-filtrated B. burgdorferi and with whole live Borrelia burgdorferi cells (strain RT1). PBMC culture conditions were 1 x 10(5) PBMC/well/ 10% autologous plasma (AP) and 2 x 10(5) PBMC/well/ 10% pooled human AB-serum (ABS). Recall antigens and Pokeweed mitogen (PWM) served as specific and nonspecific control stimuli. When whole B. burgdorferi cells were used as antigen, both the borreliosis patients (borr) and the healthy subjects (contr) reacted with an elevated stimulation index (SI) and secretion of granulocyte macrophage colony stimulating factor (GM-CSF) in vitro (SI borr. = 4; SI contr. = 3.7. GM-CSF borr. = 3.1 U/ml; GM-CSF contr. = 5.4 U/ml). A significant difference was observed when the B. burgdorferi sonicate was used. In this case, only the borreliosis patients reacted with an elevated PBMC proliferation and GM-CSF secretion (SI borr. = 6.1; SI contr. = 1.4. GM-CSF borr. = 7.6 U/ml; GM-CSF contr. = 0.3 U/ml) (p < 0.001). PMID- 8219513 TI - Efficacy of a central venous catheter (Hydrocath) loaded with teicoplanin in preventing subcutaneous staphylococcal infection in the mouse. AB - Segments (1 cm in length) of a central venous catheter (Hydrocath) coated with teicoplanin, or uncoated, were inserted subcutaneously into mice and Staphylococcus aureus or Staphylococcus epidermidis were inoculated nearby. At 24 and 48 h after infection, the mean titre of adherent bacteria (recovered by sonication) for the teicoplanin-coated catheters was less than 10 CFU as compared to more than 10(4) CFU (S. aureus) and 10(3) CFU (S. epidermidis) from the uncoated catheters. In the S. aureus infection, teicoplanin coating also prevented the formation of abscesses which were observed around uncoated catheters. PMID- 8219514 TI - Ethics of analgesia. PMID- 8219515 TI - Serotonin and its role in headache pathogenesis and treatment. AB - OBJECTIVE: This review tries to consolidate the literature on changes in serotonin and the importance of these changes for understanding headache pathogenesis and determining treatment. A model is presented that integrates previous serotonin studies and offers an explanation for apparent contradictions in the literature. DATA SOURCES: Fifty-four journal articles that described a relationship between serotonin and headache in animal and human models were identified through Medline search and bibliography and reviewed. Alterations in serotonin, headache, and clinical situations influencing headache activity were examined. DATA SYNTHESIS: Abnormalities in blood vessels have traditionally been implicated in the pathogenesis of migraine headaches, and excessive muscle contraction in tension-type headaches. Interestingly, both vascular and muscular changes occur in both migraine and tension-type headache. Recently, biochemical changes have been demonstrated in both types of headaches. These biochemical changes are postulated to precede and possibly cause the subsequent changes in blood vessels and muscle tone, known to occur in chronic headaches. Serotonin has been the most widely studied neurochemical in relation to headaches. Apparently contradictory results have been shown, such as increasing serotonin levels both increasing and decreasing headaches. CONCLUSIONS: Serotonin plays an important role in the pathogenesis of headaches. Changes in serotonin may precede the vascular and muscular changes of migraine and tension-type headaches. The influence of serotonin on headaches explains a number of clinical situations that affect headache activity and the variety of classes of effective headache medications. PMID- 8219516 TI - Functional capacity and residual functional capacity and their utility in measuring work capacity. AB - OBJECTIVE: The pain physician is often asked to establish the medical impairment of the chronic pain patient (CPP) and from that determination ascertain the work capacity of the CPP. Functional capacity (FC) testing has recently been introduced as a more objective and accurate way of facilitating the determination of work capacity. However, there are conceptual problems with the measurement of FC. These will be reviewed and the relationship of FC to residual functional capacity (RFC) will be determined. Finally, a method for measuring RFC in a job specific manner will be suggested. DATA SOURCES: The literature in reference to the measurement of medical impairment, FC, and RFC was reviewed. STUDY SELECTION: Studies appropriate to the objective of this review were selected for inclusion. CONCLUSIONS: The FC and RFC are poorly defined. Lack of definition has interfered with design of appropriate test batteries specific to work capacity. To circumvent this problem a job-specific RFC measurement method is suggested. This method is based on the Dictionary of Occupational Titles. PMID- 8219517 TI - Chronic pain in a geographically defined general population: studies of differences in age, gender, social class, and pain localization. AB - OBJECTIVE: To establish basic epidemiological data on chronic pain (duration > 3 months) in a defined population. Relationships between age, gender, and social class were tested. DESIGN: A survey of pain symptoms, including location, intensity, duration, and functional capacity, was conducted by means of a mail questionnaire. SETTING: General populations in two Swedish primary health care districts. Medical care was provided in a state health system. SUBJECTS: A random sample (from the population register) of 15% of the population aged 25-74 (n = 1,806). The response rate was 90%. OUTCOME MEASURES: Descriptive epidemiologic data in relation to objectives of the study. RESULTS: Without sex differences, 55% (95% confidence interval, 53-58%) of the population had perceived persistent pain for 3 months and 49% for 6 months. Among individuals with chronic pain, 90% localized their pain to the musculoskeletal system to a variable extent. Women experienced more multiple localizations of pain and had pain in the neck, shoulder, arm, and thigh to a greater extent than men. Prevalence of pain increased by age up to 50-59 years for both genders and then slowly decreased. The neck-shoulder area was the most common site of pain (30.2%), followed by the lower back (23.2%). Even in the youngest age groups more than one of four reported chronic pain. Blue-collar workers and employers (including farmers) reported chronic pain to a greater extent than other groups. In 13% of the population, manifest pain problems were associated with reduced functional capacity. CONCLUSION: Chronic pain symptoms are common but unevenly distributed in a general population. The results may influence planning and consultation in primary health care as well as warranting selective prevention activities. PMID- 8219518 TI - Chronic pain and the sociodemographic environment: results from the Pain Clinic at Malmo General Hospital in Sweden. AB - OBJECTIVE: To study the occurrence of chronic pain in relation to different sociodemographic factors. DESIGN AND PATIENTS: The study cohort included all 1,360 new patients who, between July 1, 1988, and June 30, 1991, were referred to the multidisciplinary Pain Clinic at Malmo General Hospital, Malmo, Sweden, because of chronic, nonmalignant pain. The patients were characterized by age, sex, type of pain (nociceptive, neurogenic, psychogenic), place of residence, and ethnic background. SETTING: The referred sample was from the municipality of Malmo, a city with 240,000 inhabitants in an industrialized area served by one hospital. RESULTS: The age and sex standardized number of patients referred per 10,000 inhabitants and year varied among the different city areas from 0.35 to 1.63. High-rate areas had, in comparison to the city average, a higher migration rate, a higher proportion of single households with children, a higher percentage of people in need of social security benefits, a higher unemployment rate, and a greater percentage of people with foreign background. The age and sex distribution differed greatly among the three pain categories. Nociceptive pain was the most common category, with a striking overrepresentation of young women. CONCLUSION: Our results support the view that the occurrence of pain in an urban population is related to a number of sociodemographic factors. Further studies should be performed to evaluate how these factors influence incidence, medical seeking behavior, clinical course, and rules for referral. PMID- 8219519 TI - Intercorrelation and test-retest reliability of the Pain Disability Index (PDI) and the Oswestry Disability Questionnaire (ODQ) and their correlation with pain intensity in low back pain patients. AB - OBJECTIVE: To determine the intercorrelation between subjective disability, as assessed with the Pain Disability Index (PDI) and the Oswestry Disability Questionnaire (ODQ) and their correlation with visual analogue scale (VAS) pain intensity ratings. DESIGN AND SUBJECTS: Questionnaires were administered to 94 patients with chronic low back pain with or without radiation into the legs of at least 3 months' duration. SETTING: Tertiary care center. RESULTS: High correlations were noted between the ODQ and PDI (r = 0.83) and PDI factor 1 (r = 0.84), a subscale of the PDI. Lower correlations were noted between pain intensity (VAS) scores and the ODQ (r = 0.62) and the PDI (r = 0.69). A weaker correlation (r = 0.41) was noted between the ODQ and PDI factor 2. Intraclass correlation coefficients (ICC) for test-retest reliability in 20 patients (time interval 1 week) were for the ODQ ICC = 0.83, PDI ICC = 0.91, PDI percentage score ICC = 0.91, PDI factor 1 ICC = 0.87, and PDI factor 2 ICC = 0.73, respectively. CONCLUSIONS: The present results suggest that either the PDI or the percentage score PDI and also the even shorter-to-administer PDI factor 1 may be useful and reliable tests for the assessment of subjective disability in low back pain patients. As noted by the moderate intercorrelations with pain intensity scores, both the PDI and the ODQ address a broader concept of disability than that directly related to pain intensity. PMID- 8219520 TI - Altering beliefs about pain and impairment in a functionally oriented treatment program for chronic low back pain. AB - OBJECTIVE: This study examined pain and impairment beliefs [measured with the Pain and Impairment Relationship Scale, (PAIRS)] of chronic low back pain patients during rehabilitation and hypothesized that pain beliefs would be stronger in drop-out subjects, decrease during treatment, and after treatment correlate strongly with disability measures. DESIGN: Prospective cohort. SETTING: Outpatient, functionally oriented rehabilitation program for chronic low back pain. PATIENTS: 72 consecutive chronic low back pain referral patients disabled from working because of pain. INVOLVEMENT: Interdisciplinary rehabilitation with a focus on intensive physical reconditioning was employed. OUTCOME MEASURES: Program completion versus drop-out groups and pretreatment and posttreatment pain, disability, depression, and PAIRS scores were compared. RESULTS: Thirty patients dropped out and 42 subjects completed treatment. The PAIRS scores at evaluation were similar for both groups. The PAIRS scores improved significantly during treatment (p < 0.001). Posttreatment PAIRS scores correlated highly with disability measures (r = 0.79, p < 0.001). CONCLUSION: Pain beliefs are of minimal value for predicting treatment compliance, but may be altered during functionally oriented treatment of chronic low back pain. Posttreatment disability closely mirrored attitudes and belief-associated pain and impairment. PMID- 8219521 TI - The relationship of cognitive distortion to depression in chronic pain: the role of ambiguity and desirability in self-ratings. AB - OBJECTIVE: This study attempts to clarify the relationship between depression and the cognitions of chronic pain patients. It was hypothesized that the ambiguity and desirability of self-rated traits would significantly predict level of depression. DESIGN: The study incorporated a correlational design in which subjects rated a number of traits as they pertained to themselves and completed questionnaires on negative affect and pain. SETTING: Subjects were recruited from a Spine Program and the Orthopaedic Clinic, at a tertiary care facility at the University of Florida. SUBJECTS: Fifty-eight chronic pain patients, two thirds of whom had primary back pain, were recruited for the study. OUTCOME MEASURE(S): All subjects completed a Beck Depression Inventory and McGill Pain Questionnaire, and rated themselves on 28 traits characterized by the dimensions of desirability and ambiguity. RESULTS: A hierarchical regression analysis indicated that the subjects' self-ratings on ambiguous negative traits significantly predicted level of depression. CONCLUSIONS: Patients with chronic pain are more likely to acknowledge undesirable traits in themselves when they have higher levels of depression when the pain level was controlled. These findings may have important implications for the cognitive-behavioral treatment of chronic pain patients. PMID- 8219522 TI - Sensory and pain thresholds to orofacial argon laser stimulation in patients with chronic burning mouth syndrome. AB - OBJECTIVE: Psychophysical assessments of orofacial sensory function were performed in order to investigate neurophysiological aspects of the burning mouth syndrome (BMS). DESIGN: Sensory and pain thresholds to brief argon laser stimulation were determined on six test regions, which included the tip of tongue, the lower lip mucosa and skin, the buccal mucosa, the anterior hard palate, and the dorsum of the hand. SETTING: The experimental examination was performed at the Pain Clinic Unit at the Royal Dental College. PATIENTS: Twenty three elderly denture-wearing patients diagnosed as suffering from BMS were studied, and a control group included 23 age-, sex-, and denture-matched subjects. The obtained thresholds were compared between groups. RESULTS: Sensory thresholds were significantly higher and ratios between pain and sensory thresholds significantly lower in patients with BMS on all the tested regions. Pain thresholds were significantly elevated on the lower lip skin, the anterior hard palate, and the hand in patients with BMS. At sensory threshold level, a faint pinprick perception was often reported by patients with BMS contrary to a perception of warmth described by control subjects. The intraregional variations in sensory and pain thresholds on the hard palate, the lower lip mucosa, and on the skin were similar in both groups, but differences occurred in sensory thresholds on the tongue in patients with BMS. CONCLUSIONS: The presence of abnormal prepain perceptions and disturbances in the perception of nonnociceptive and nociceptive thermal stimuli applied on both pain-affected and normal regions suggest a perceptual deficit unrelated to specific pathophysiological mechanisms in BMS. However, it appears that a psychological explanation of BMS should be used cautiously, as the present results suggest alterations in sensory function. PMID- 8219523 TI - Sine-wave auricular TENS produces frequency-dependent hypesthesia in the trigeminal nerve. AB - OBJECTIVE: To evaluate the effects of different frequencies of auricular (ear-to ear) sine-wave transcutaneous electrical nerve stimulation (TENS), administered at subliminal intensity, on trigeminal nerve sensitivity. DESIGN: In a double blind protocol, healthy volunteer subjects were administered one of three different frequencies of active TENS (5, 100, or 2,000 Hz) or placebo TENS (no current was passed) for 30 min. SETTING: Department of Psychology, City University of New York. SUBJECTS: 72 healthy undergraduate volunteers with no preexisting pain problems (16 men and 56 women), from the Department of Psychology, City University of New York. OUTCOME MEASURE: Pretreatment to posttreatment changes were measured in sensation threshold for a 250-Hz electrical stimulus applied transcutaneously to an area 1 cm anterior to the tragus of the ear (mandibular division of the trigeminal nerve). RESULTS: Analysis of variance indicated no group differences in baseline trigeminal sensation threshold, but there were significant group differences in pretreatment to posttreatment changes in sensation threshold (p < 0.001). A postiori analysis showed significant increases in trigeminal sensation threshold after active TENS as compared to placebo TENS (p < 0.05), with 5- and 100-Hz TENS producing significantly greater hypesthesia than 2,000-Hz TENS (p < 0.05). CONCLUSIONS: Sine-wave auricular TENS produces frequency-dependent trigeminal hypesthesia that is not a placebo effect. PMID- 8219524 TI - Neuropathic pain in a cancer patient responding to subcutaneously administered lignocaine. AB - OBJECTIVE: To demonstrate difficulties encountered in alleviating neuropathic pain in a terminally ill cancer patient, with the very tentative diagnosis of postherpetic neuralgia. SETTING: A multidisciplinary pain department in a university hospital. PATIENTS: A patient with Hodgkin's lymphoma and leiomyosarcoma in the liver developed an unusual manifestation of neuropathic pain. INTERVENTION: Oral drug treatment with morphine associated with amitriptyline, valproic acid, mexilitine, flufenazine, and methylprednisolone failed to suppress pain attacks. Only the subcutaneous instillation of lidocaine (2 mg/kg/h) could partially suppress pain. A dorsal root entry zone lesion intervention could only temporary stop the pain attacks. Infiltration and nervous stimulation techniques were not helpful. OUTCOME MEASURES: In determining pain control, the visual analog scale rating scale and the number of attacks per hour were considered. RESULTS: Only the subcutaneous administration of lignocaine could partially suppress pain. Because of the patient's poor hepatic circulation, variable lidocaine plasma concentrations were responsible for intolerable side effects. CONCLUSIONS: Subcutaneous lignocaine administration remains a useful method in treating neuropathic cancer pain. The poor metabolic condition of the patient can lead to deleterious high plasma levels. A dorsal root entry zone lesion could only temporarily stop the pain. PMID- 8219525 TI - Relationships between self-reported symptoms of infection, menstrual-cycle related distress, and cycle phase. AB - This study examined the relationships between symptoms of common infectious illnesses, menstrual cycle phase, and cycle-related distress. Sixty-five women who had regular menstrual cycles and were not taking birth control pills were the convenience sample for this research. Subjects completed the Menstrual Distress Questionnaire (MDQ), the Perceived Stress Scale (PSS), and an investigator developed symptom checklist (SCL) that inventoried symptoms of common respiratory, skin, gastrointestinal, and genitourinary infections. The subjects completed all questionnaires three times during the menstrual cycle (during menstruation, midcycle, and premenstruum). The results of the study indicated a highly significant clustering of infectious illness symptoms during the perimenstrual period compared with midcycle. There were significant relationships between scores on the MDQ and PSS and the frequency and intensity of infection symptoms throughout the cycle. Analysis of covariance (ANCOVA) of the effects of phase, PSS, MDQ, and SCL scores revealed that phasic influences were not significant when MDQ scores were controlled. PSS and MDQ scores significantly influenced symptom scores when phase was controlled, suggesting a general relationship between distress and infectious symptoms during the menstrual cycle. PMID- 8219526 TI - Cardiac response of trained and untrained males to a repeated psychological stressor. AB - The authors examined cardiac response to repeated exposure to a psychological stressor of aerobically conditioned (n = 15) and unconditioned subjects (n = 15). Heart rate and electrocardiographic T-wave amplitude responses of 10 trials of the Stroop Test were monitored during and after performance. Both groups' adaptation patterns were similar, with a plateauing of heart rate response after the third trial. Compared with the unconditioned group, however, the aerobically conditioned subjects recorded lower absolute heart rate responses during and after the stressor for every trial. Relative heart rate responses during the stressor and recovery were similar for both groups. There was also no difference between groups in T-wave response during or after the stressor. These data suggest that absolute heart rate response during and after repeated exposure to a psychological stressor is lower for aerobically trained individuals. PMID- 8219527 TI - The relative effectiveness of three reminder letters on making and keeping mammogram appointments. AB - One hundred fifty women who had previously had at least one mammogram were sent one of three prompt letters informing them that they were due for screening. The letters were either reassuring, anxiety provoking, or the standard hospital prompt. Based on a review of the literature, we hypothesized that the reassuring letter would be most effective in motivating women to schedule and keep appointments, the anxiety-provoking letter would produce an intermediate level of compliance, and the standard hospital letter would be least effective. Our hypothesis was partially supported. Overall, 45% of the women in the study scheduled mammogram appointments. This included 54% of those who received the reassuring letter, 42% of those who received the anxiety-provoking letter, and 38% of those who received the standard letter. Although the results were in the predicted direction, the results of a chi-square test indicated that differences among groups were not statistically significant. When the dependent measure was number of appointments kept, rather than scheduled, however, significantly more women who received the reassuring letter actually kept their appointments compared with those who received the standard hospital letter. Subsequent analyses suggested that having a family history of breast cancer, receiving a reassuring letter, and being older than 50 years were important factors in scheduling appointments. PMID- 8219528 TI - Effects of psychological stress on cold pressor test results. AB - The authors evaluated the incidence of a psychological stressor in the modification of blood pressure induced by the cold pressor test in normotensive and medicated hypertensive subjects. The study was carried out in two stages: In the first, 28 (14 normotensive and 14 hypertensive) subjects were administered a cold pressor test. Fifteen days later, 14 subjects repeated the same experiment. The remaining 14 subjects (7 hypertensive and 7 normotensive) also repeated the cold pressor test, with the difference that, to add a stressful psychological situation, the physician "abandoned" them at the beginning. The addition of the psychological stress significantly increased only systolic blood pressure in both the hypertensive and the normotensive subjects. Furthermore, the hypertensive subjects did not recover their basal blood pressure values following the cold pressor test when the psychologically stressful situation had been added. These results show the importance of considering psychological aspects when applying physical pressor tests. PMID- 8219529 TI - The role of state-trait anxiety in insomnia and daytime restedness. AB - This study examined the relationships among anxiety, nocturnal sleep, and daytime restedness over a 1-week period, using the Spielberger State-Trait Anxiety Inventory and daily sleep logs. Among both insomniacs and controls, between subjects correlations showed a significant negative relationship between state anxiety at bedtime and restedness during the day. Neither variable was related to nocturnal sleep variables. Within-subject correlations showed similar relationships between state anxiety and restedness the following day. For insomniacs, but not for normal sleepers, bedtime state anxiety was also significantly correlated with sleep latency. The authors hypothesize that anxiety, not sleep deprivation, may be responsible for the insomniac's complaint of daytime fatigue. PMID- 8219530 TI - Renal hemodynamics and cardiovascular reactivity in the prehypertensive stage. AB - To examine whether sympathetic nervous activation has an impact on renal circulation in subjects at risk for high blood pressure, we assessed renal hemodynamics and cardiovascular response to mental stress in 40 healthy young white males, 12 normotensive subjects without and 14 with familial hypertension, and 14 with borderline hypertension. The response of systolic and diastolic blood pressure to mental stress was assessed while each patient performed a mental arithmetic task; this was taken as the parameter for the activation of the sympathetic nervous system. Renal plasma flow was measured by para-aminohippuric acid clearance under steady-state conditions. In parallel, glomerular filtration rate as a parameter for functional impairment of the kidneys was determined by creatinine clearance, and filtration fraction was also calculated. Patients with borderline hypertension were characterized by a reduced renal blood flow and increased filtration fraction in comparison with both normotensive groups. The increase in systolic blood pressure during mental stress was more pronounced in borderline hypertensives. We observed no significant difference in renal hemodynamics and cardiovascular response to mental stress between normotensives with and without a family history of hypertension. In the total population, cardiovascular response to mental stress was correlated with renal hemodynamics: The greater the increase in systolic blood pressure during mental stress, the lower was the renal plasma flow and the greater the filtration fraction. Thus, renal plasma flow was found to be already reduced and filtration fraction increased before sustained hypertension developed. Because this pattern in renal hemodynamics was related to cardiovascular response to mental stress, our data suggest that sympathetic activation already appeared to affect renal hemodynamics at the onset of essential hypertension. PMID- 8219531 TI - The extracardiac total cavopulmonary connection for definitive conversion to the Fontan circulation: summary of early experience and results. AB - Between July 1991 and March 1993, five children (ages 2 to 6 years) with complex congenital heart disease have undergone a new operation for conversion to the Fontan circulation. This procedure combines a bidirectional Glenn shunt with an extracardiac lateral tunnel (ELT) to carry systemic venous return to the pulmonary arteries (PAs). The ELT was constructed so that the circumference consists of Gore-Tex (2/3) and lateral epicardial atrial wall (1/3). The ELT can be performed with all varieties of single ventricle physiology, as in our patients with tricuspid atresia (n = 3), dextrocardia (n = 1), and situs inversus with levocardia (n = 1). PA reconstruction was required in four patients. At follow-up from 1 to 20 months, all patients are in New York Heart Association Class I and in normal sinus rhythm. Postoperative catheterization has revealed low PA pressures (< or = 12 +/- 1 mmHg) and angiography has shown excellent ELT function with brisk flow into the PAs bilaterally. All patients maintain an O2 saturation > 94% on room air. The advantages of this new extracardiac modification of Fontan's operation are: (1) aortic cross-clamping is not usually required; (2) incorporation of lateral atrial wall in ELT allows for growth while permitting construction of a fenestration or adjustable atrial septal defect in high risk patients; (3) absence of atriotomy and intraatrial suture lines may decrease late risk of arrhythmias; (4) early or late baffle leaks cannot occur; (5) intraatrial obstruction from the baffle cannot occur; (6) coronary sinus remains in low pressure atrium; and (7) hydrodynamic benefits of the total cavopulmonary connection are preserved. We recommend this procedure for patients undergoing surgical conversion to the Fontan circulation. PMID- 8219532 TI - A surgical technique for a delayed hemorrhage after lateral aortorrhaphy. AB - Stretching of suture material is an infrequent cause of delayed mediastinal hemorrhage after lateral repair of the aorta. In contrast to end-to-end reconstructions, lateral patch repairs of the aorta present unusual stress on the anastomotic suture line. We describe a simple technique for repair of loosened suture lines, with suggestions for preventing this complication in cases of lateral aortic reconstruction. PMID- 8219533 TI - Video-assisted thoracoscopic division of a vascular ring in an infant: a new operative technique. AB - We report the first successful use of thoracoscopy and video-assisted thoracic surgery (TVATS) techniques to relieve extrinsic tracheoesophageal compression produced by a vascular ring. The patient was a 3-month-old infant with postprandial regurgitation and a diagnosis of double aortic arch. After an uncomplicated operation and recovery, the infant was discharged on the second postoperative day. Refinement of technique and instrumentation may allow wider application of video-assisted thoracoscopic techniques in pediatric patients. PMID- 8219534 TI - Neck cannulation for the repair of thoracic artery aneurysms in the infant. AB - Thoracic aneurysms are relatively rare in infancy. We report our experience with two such patients, one with a false aneurysm of the ascending aorta and the other with a mycotic aneurysm of the main pulmonary artery. Neck cannulation prior to sternotomy, using cannulae designed for extracorporeal membrane oxygenation, allowed entry into the mediastinum under controlled circumstances and permitted the successful repair of the aneurysms. PMID- 8219535 TI - Reducing neurological complications after cardiac transplantation: technical considerations. AB - As the survival rate for cardiac transplantation improves, attention focuses on morbid events that occur perioperatively. Neurological problems have been recognized after transplantation, and appear to have multiple etiologies including thromboembolism, hypoperfusion syndromes, cerebral hemorrhage, and drug toxicities. Since 1988, 113 consecutive adults with end-stage cardiomyopathy were transplanted using a surgical technique that emphasizes precise everting atrial and great vessel anastomoses, a modified order of anastomoses, continuous endocardial and topical cold irrigation, and careful de-airing of the heart. Although a significant fraction of the patients were at high risk for cerebral events, the incidence of early and late neurological complications were each under 2%. The rate of early graft dysfunction was low and no patient was found to develop intracardiac thrombus on intermediate-term follow-up. These technical modifications may contribute to improved neurological outcomes after transplantation. PMID- 8219536 TI - The role of transesophageal echocardiography in the monitoring of cardiac mass removal: a review of 17 cases. AB - Intraoperative transesophageal echocardiography (TEE) was used to monitor the removal of intracardiac masses in 17 patients. Prebypass TEE was used to confirm the preoperative diagnosis. It gave a clear image and anatomical definition of the mass in 16 cases. Moreover, in 11 of these patients, prebypass TEE provided information not obtained previously by traditional exams. This information was judged either useful or indispensable for a successful outcome in 10 of these patients. However, in one of the remaining six patients, TEE did not clearly visualize a flat thrombus in the left atrium. Postbypass TEE was used in each case to monitor the surgical results of the mass removal and the associated procedures. In one patient, it disclosed a progressively expanding hematoma in the left atrial wall, which was interfering with mitral valve function. From this experience, we consider intraoperative TEE the best monitoring device during cardiac mass removal because it usually provides a more complete diagnosis and anatomical definition of the mass than the traditional preoperative methods and permits monitoring of the surgical results before chest closure. Some limitations to this method may exist. PMID- 8219537 TI - Use of venous fistula technique for intraoperative cardiac hemorrhage. AB - We describe an innovative technique to control hemorrhage after right atrial wall reconstruction in a patient with primary angiosarcoma. At the time of surgery, the tumor was found to involve all of the free wall of the right atrium and a superficial layer of the right ventricle. A pericardial patch was used to reconstruct the right atrial wall; however, there was diffuse coagulopathy with bleeding from the anastomoses and remaining tumor. To tamponade the bleeding, a Dacron patch was sewn to the right edge of the pericardium, around the right ventricle and right coronary artery, but with little improvement in the bleeding. A type of Cabrol fistula was then formed with a tube graft from the Dacron patch to the left innominate vein. This acted as a conduit back into the venous system, with the blood taking the path of least resistance. Hemostasis was then achieved, allowing the patient to be taken to the intensive care unit. PMID- 8219538 TI - Modified Cabrol's technique for composite replacement of the aortic valve and ascending aorta. AB - Composite replacement of the ascending aorta and aortic valve with coronary reimplantation can be complicated by intraoperative hemorrhage from the coronary ostial anastomoses and proximal aortic suture line. Exposure and repair of these suture lines may be quite difficult after the termination of bypass in the intact aortic root. Cabrol originally described connecting the coronary ostia by separate Dacron graft, which was then anastomosed side-to-side to the aortic conduit, and the entire repair wrapped in the aneurysm wall to control bleeding. This article describes a modification of Cabrol's technique in which coronary ostial buttons are mobilized and the entire aortic wall resected. This procedure has been used in five patients with varied pathology, with no perioperative deaths and one minor intraoperative neurological event. The greater ease of operation and improved hemostasis afforded by the technique described in this article warrant its consideration in patients requiring aortic root replacement, and may prove particularly helpful in complex cases and reoperations. PMID- 8219539 TI - Replacement of chordae tendineae using expanded polytetrafluoroethylene (ePTFE) sutures during mitral valve replacement in patients with severe mitral stenosis. AB - Since September 1991, 20 patients with mitral stenosis underwent mitral valve replacement and chordal replacement with expanded polytetrafluoroethylene (ePTFE) sutures. The continuity between the papillary muscles and the mitral annulus was maintained by four mattress sutures of ePTFE, which connected the stumps of the papillary muscle heads to the mitral annulus at the 2, 4, 8, and 10 o'clock positions. Low profile bileaflet prosthetic valves were inserted. There was no mortality either in-hospital or during follow-up. There was no valve related morbidity, such as valve structural failure, thromboembolism, anticoagulant related hemorrhage, prosthetic valve endocarditis, or posterior left ventricular rupture. The technique of replacing chordae tendineae is described in detail. PMID- 8219540 TI - Erythropoietin in cardiac surgery. AB - Erythropoietin is the primary growth factor for red blood cells. A glycoprotein hormone synthesized by the kidneys, erythropoietin serves to increase red blood cell production in response to tissue hypoxia. It exerts its effect by increasing the numbers of erythroid progenitor cells in the bone marrow, and by increasing the rate at which their development is accomplished. With the introduction of recombinant erythropoietin in 1987, an important pharmacological agent became available for the manipulation of erythropoiesis. While used primarily for the treatment of the anemia of renal failure, recombinant erythropoietin has also shown usefulness in treating other types of anemias in which the endogenous erythropoietin response is insufficient. Perioperative use of the drug grew as a natural extension of this, and erythropoietin has been applied to correct preoperative anemia, augment autologous blood donation, and improve postoperative red cell recovery. Analysis of these perioperative clinical studies reveals success in these areas, but it also reveals that closer attention to the physiology of the natural response, and to the pharmacology of the recombinant product, might significantly improve results. Such an improvement in efficacy is both desirable and necessary when use of the drug is viewed in the setting of today's changing health care environment. By optimizing dosing schedules and targeting the drug to those most at risk for red cell transfusion, recombinant erythropoietin will likely become an important tool in efforts to achieve the elusive goal of bloodless cardiac surgery. PMID- 8219541 TI - An analysis of failures in primary cervical anterior spinal cord decompression and fusion. AB - Recently, postoperative results of cervical spondylosis, disc herniation, and ossification of the posterior longitudinal ligament (OPLL) after anterior cervical surgeries have improved. However, occasional unsatisfactory cases needing a second operation remain. We analyzed and developed strategies for multioperated neck (MON) cases; all patients had two operations. From 1965 to 1988, 443 cervical anterior surgeries were performed in our hospitals; 53 (12.0%) of these patients needed second operations. These MON cases were classified by the following causes: pseudarthrosis, graft fracture, insufficient decompression, misdiagnosis, and adjacent disc problems. These groups were analyzed, and the resulting surgical strategies, including indications and techniques of anterior surgery, are described. PMID- 8219542 TI - A comparison of computed tomography-myelography, magnetic resonance imaging, and myelography in the diagnosis of herniated nucleus pulposus and spinal stenosis. AB - The sensitivity, specificity, and accuracy of computed tomography (CT) myelography, magnetic resonance imaging (MRI), and myelography in making the diagnosis of herniated nucleus pulposus (HNP) and spinal stenosis were compared in a retrospective study involving 59 surgical procedures in 57 patients who had all three tests performed preoperatively. One hundred nineteen levels were surgically explored for evidence of HNP and spinal stenosis. The results of each test were correlated with what was found at each surgical level explored. Overall, myelo-CT was the most accurate test for diagnosing HNP (76.4%) as well as the most sensitive (77.8%), whereas myelography was the most specific (89.2%). In making the diagnosis of spinal stenosis, myelo-CT and MRI were equally accurate (85.3%) and sensitive (87.2%), whereas myelography was the most specific (88.9%). In a special subset of patients who had revision surgery, the accuracy rate in diagnosing spinal stenosis or HNP was highest with MRI (84.9%), as was the sensitivity (69.2%) and specificity (95%). According to the results obtained from this series of patients, myelo-CT seems to be the most sensitive and accurate test in diagnosing HNP and spinal stenosis, whereas myelography is the most specific, although no statistical significance was noted in this study. However, because MRI did compare favorably with myelo-CT in most instances, particularly in revision surgery; it may be the procedure of choice due to its noninvasiveness and relative lack of side effects. PMID- 8219543 TI - Serum cefazolin levels during spinal fusion: effect of blood loss and duration of surgery. AB - Perioperative cefazolin prophylaxis is commonly employed in posterior spinal fusion (PSF) procedures, which are often lengthy and involve significant blood loss. In this study, serum levels of prophylactically administered cefazolin were measured serially during spinal fusion procedures, and the possible relationship of antibiotic concentrations to blood loss and fluid therapy were examined. Serum antibiotic levels, measured at 30-min intervals, declined with a half-life of 90 min, similar to the previously reported experience with normal adult volunteers. There was no relationship between serum half-life and blood loss or fluid replacement. An explanation for these findings is offered, along with recommendations for dosing. PMID- 8219544 TI - Traumatic occipitoatlantal dislocations. AB - Fourteen occipitoatlantal dislocations were treated during an 11-year period. All patients presented with neurological deficits and definite evidence of spinal instability. Plain radiographs provided the diagnosis conclusively in 11 patients. Three patients required computed tomography (CT) or magnetic resonance (MR) imaging for diagnosis. Rotational subluxations were radiographically occult and associated with less severe neurological injuries compared to distracted or translated subluxations. Ten patients died acutely. One patient, who had complete C1 level quadriplegia, died after 3 months. Three patients with incomplete spinal cord syndromes had long-term survival and functional neurological recoveries. Extensive ligamentous injury predisposed patients to recurrent subluxations. In several patients, traction or a cervical collar caused distraction and neurological injury. Halo immobilization and urgent fusion are necessary for patients with salvageable neurological function. Nonoperative measures are inadequate for immediate or long-term spinal stability. PMID- 8219545 TI - The ultimate flexural strength of the lumbar spine and vertebral bone mineral content. AB - Flexion-distraction injuries (lap seat-belt injuries resulting from car accidents) were simulated by exposing 16 lumbar functional spinal units (FSUs) to a combined quasistatic load of bending and shearing in the sagittal plane. The load response of the FSU was measured by means of a force and moment transducer. Displacements and angulations were measured and calculated by means of dial gauges and photographs taken after each loading step. The mean angulation between the vertebrae just before total rupture was 20 degrees. The ultimate values of bending moment, shear force, and bending stiffness were correlated with the bone mineral content (BMC), and so were the horizontal and vertical displacements determined around the yield point on the load-displacement curve. PMID- 8219546 TI - The results of chemonucleolysis as a function of three dimensional volumetric analysis of disc herniation. AB - Spinal canal and dural sac morphometry as demonstrated by CT scan analysis in patients undergoing chemonucleolysis for the treatment of herniated lumbar discs was analyzed in an attempt to develop a method of predicting positive or negative follow-up clinical results. The morphometry of the canal and dural sac at the intervertebral disc level was defined by reviewing normal levels of CT scans. Levels with herniated discs were then analyzed for comparison of treatment results between successful and unsuccessful procedures. The concept of spinal reserve capacity was evaluated. Significant differences between canal morphometric parameters of patients with treatment success or failure were then identified. The concept of spinal reserve capacity may be applicable in spinal stenosis, but we were unable to delineate any predictive value in the evaluation of patients with herniated lumbar discs undergoing chemonucleolysis. PMID- 8219547 TI - Reexamination of the Cobb and Ferguson angles: bigger is not always better. AB - In scoliosis, the Cobb measure of curve severity has been recommended over the Ferguson method because it had greater magnitude and appeared more sensitive to changes during progression and after treatment. This study made comparisons between the Cobb and Ferguson measures in radiographs of patients with idiopathic scoliosis to test whether the methods were really different, and to compare their precision. In 138 observations of 77 untreated patients there was a very high correlation (R2 = 0.98) between Cobb and Ferguson angle, with Cobb angle averaging 1.35 times greater. For sequential measures (mean interval 10 months), the percent changes agreed closely (R2 = 0.5). The relationship between Cobb and Ferguson angles remained the same in measurements of 24 patients wearing a brace compared with the unbraced condition and in 18 patients measured before and after Harrington rod surgery. Repeated measurements were made by three observers with the apex and end vertebrae pre-marked and held constant. For Cobb angle, the greatest range of measurements on any film was 8 degrees (pooled SD = 1.3 degrees). For Ferguson angle the greatest range was also 8 degrees (pooled SD = 1.8 degrees). Ferguson angle was slightly more sensitive to incorrect selection of end vertebrae. It was concluded that both methods can be useful for measuring curve magnitude. Ferguson angle should be measured and then adjusted by multiplying it by 1.35 in situations where Cobb angle measurement is technically difficult or invalid. Ferguson angle is better suited to automated measurement. PMID- 8219548 TI - Ability of Cotrel-Dubousset instrumentation to preserve distal lumbar motion segments in adolescent idiopathic scoliosis. AB - Between 1985 and 1990, 44 patients with adolescent idiopathic scoliosis were treated with Cotrel-Dubousset instrumentation when Harrington instrumentation would have extended into the distal lumbar spine (L3, L4, or L5) for these curve patterns. Twenty-four of these 44 (group I) patients had one distal fusion level preserved using Cotrel-Dubousset instrumentation, whereas the other 20 patients (group II) were instrumented/fused with Cotrel-Dubousset instrumentation to the expected Harrington instrumentation level in the lower lumbar spine. All patients have a minimum 2-year follow-up, and the average follow-up is 39 months (range 24 74). The characteristics of the group I curves that allowed us to stop the instrumentation a level short included minimal rotation and tilt of the anticipated lowest instrumented vertebra, overall coronal curve flexibility, and nonstructural components to the lumbosacral region of the spine. There were no major differences between these two groups when comparing postoperative coronal and sagittal balance parameters at the most recent follow-up. In select cases, dependent on the preoperative criteria to be discussed, Cotrel-Dubousset instrumentation (vs. traditional Harrington instrumentation) does allow distal lumbar fusion levels to be saved while maintaining acceptable coronal and sagittal balance. PMID- 8219549 TI - Upper lumbar disc herniations. AB - This study reviews the presentation, diagnosis, and outcomes of upper lumbar disc herniations (L1-2, L2-3, L3-4). One hundred forty-one patients operated upon at three centers between 1980 and 1990 were analyzed (102 men, 39 women; 3 L1-2, 21 L2-3, 117 L3-4; average age 51.6 years; 10.4% of all lumbar discectomies performed). Preoperative signs and symptoms were highly variable. Sensory, motor, and reflex testing was variable and potentially misleading in suggesting a level of herniation. In analyzing radiographic studies (noncontrast CT, myelography, MRI) individually and using other radiographic studies and operative findings as a standard for comparison, a high false-negative rate was found for all studies when considered individually, especially at the higher L2-3 level. Intraoperative radiographs were employed with increasing frequency as the level of herniation ascended. Six operative complications (4.3%) were identified, all of which were treated and were resolving at the time of discharge. Follow-up obtained at an average of 2.2 years in 87% of patients by chart review showed no reoperations or late complications. Noncompensation patients had a significantly higher percentage of good/excellent results (86%) than those with compensation or legal claims pending (45% good/excellent results). Based upon these data, we recommend myelogram with postmyelogram CT and/or MRI in the workup of these patients and intraoperative radiographs in all cases when decompressing an upper lumbar disc herniation. Patients with compensation/legal claims should be approached cautiously, because their subjective results are significantly worse than those of noncompensation patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219550 TI - Os odontoideum. PMID- 8219551 TI - Percutaneous transhepatic drainage of the nondilated biliary system. AB - PURPOSE: The authors sought to develop a safe, efficacious technique for percutaneous transhepatic drainage of nondilated biliary systems. PATIENTS AND METHODS: Twenty-three drainage procedures were performed on 14 consecutive patients with nondilated ducts. Fourteen procedures were carried out for primary placement of a transhepatic biliary drain, eight for placement of a second drain, and one for placement of a third drain. Drainage catheter access into the biliary tree was gained via direct puncture of a peripheral duct (fourth order or smaller branch) in four procedures. In the remaining 19 procedures, peripheral duct punctures were facilitated by retrograde passage of a 5-F catheter from a previous, remote percutaneous access site into the fourth-order duct to be punctured. Nine of these 19 duct punctures were facilitated by the use of a nitinol Goose Neck snare passed through the intraductal catheter. RESULTS: Of the access methods used, the nitinol snare technique was the fastest. Successful peripheral access was achieved in all patients without bleeding complications. One patient developed symptoms of bacteremia, which resolved within 12 hours with antibiotic therapy and external biliary drainage. CONCLUSION: Percutaneous peripheral access can be achieved safely in the nondilated biliary tree and can obviate surgery for some patients and facilitate future interventions. PMID- 8219553 TI - Bilateral percutaneous biliary drainage in a patient with hilar biliary obstruction and multifocal hydatid liver disease. PMID- 8219552 TI - Bilateral internal biliary drainage of hilar cholangiocarcinoma with modified Gianturco Z stents inserted via a single percutaneous tract. AB - PURPOSE: Modified Gianturco Z stents were used in five patients with hilar cholangiocarcinoma to permit bilobar hepatic drainage via a single percutaneous tract. PATIENTS AND METHODS: After successful negotiation of strictures from the ipsilateral hepatic duct to the contralateral hepatic duct and the common bile duct, a modified endoprosthesis--made by connecting two double-body Z stents with two stainless steel wires in order to leave a space in between--was implanted in one stricture and a 'space' was located at the hepatic confluence. A second endoprosthesis, a two- to six-body Z stent, was introduced into the second stricture through the 'space' of the initial endoprosthesis and was implanted so that a part of the endoprosthesis should overlap the initial endoprosthesis. RESULTS: Optimal positioning of the two endoprostheses was successful in all patients. CONCLUSION: The technique seems simple, safe, and reliable in reconstructing the bilateral hepatic ductal systems via a single percutaneous approach in patients with hilar cholangiocarcinoma. PMID- 8219554 TI - Suggested standard terms for interventional procedures. PMID- 8219555 TI - Risks and benefits of manipulation of the titanium Greenfield inferior vena cava filter after deployment: filter facts and filter fantasies. PMID- 8219556 TI - Experimental studies of portal venous embolization with iodized oil in rats with experimentally induced liver cancer. AB - PURPOSE: To assess the feasibility of portal venous embolization (PVE) with iodized oil in the treatment of human hepatocellular carcinoma (HCC), the distribution of iodized oil after PVE and tumor vascularity after hepatic arterial embolization (HAE) with iodized oil was determined in 25 rats with n nitrosodiethylamine-induced liver cancer. MATERIALS AND METHODS: Under microscopic guidance, HAE with 1 mL of iodized oil was performed in 10 rats. After HAE, low-kilovoltage radiography in four rats and Microfil perfusion techniques in six were used to investigate the distribution of iodized oil and the portal blood supply, respectively. Low-kilovoltage radiography and histologic examination were performed to observe the distribution of iodized oil in 15 rats after PVE with doses of 0.6 mL/kg in each rat. RESULTS: After HAE with iodized oil, it was common that tumor nodules smaller than 5 mm in diameter were filled with Microfil perfused through the portal vein. After PVE, tumor nodules (< 5 mm) were completely filled with iodized oil, while filling defects were observed in larger tumor nodules (> 5 mm), which could have been filled through hepatic arterial perfusion. CONCLUSION: PVE with iodized oil may have a role in the treatment of hepatic malignant tumors, and it may play an important role in early detection and treatment of small tumor nodules (< 5 mm) supplied mainly by the portal vein. PMID- 8219557 TI - Long-term patency of Wallstent endoprostheses in benign biliary obstructions: experimental results. AB - PURPOSE: Coated and noncoated Wallstents were implanted in dogs with experimental benign common bile duct stenoses to monitor the long-term patency of self expanding stents in the biliary system. MATERIALS AND METHODS: Experimental common bile duct stenoses were induced with a thermal laser in 12 dogs. Three silicone-coated and 14 noncoated stents were implanted. The animals were followed up from 3 to 25 months by means of cholangiography, cholangioscopy, measurements of liver enzyme levels, autopsy, and histology. RESULTS: Silicone coated stents failed in all cases, resulting in two total occlusions and one stent dislodgment to the bowel. Noncoated stents led to marked mucosal hyperplasia and stent narrowing in most cases, but with follow-up of more than 12 months, hyperplasia underwent regression and--except in one case--neither an increase in liver enzyme levels nor stent occlusion occurred. Histologically, the extent of hyperplasia was related to the stent position within the duct wall. With stents in the mucosal layer, hyperplasia was excessive. Once the stent entered the submucosal layer, hyperplasia was decreased. CONCLUSION: In an experimental setting, mucosal hyperplasia did not compromise patency of noncoated stents in benign bile duct stenosis and regressed with late follow-up after 12 months. PMID- 8219558 TI - Response of Wallstents to dilation: therapeutic implications. AB - PURPOSE: The authors document the degree of in vitro shortening of the Wallstent when expanded to different diameters and demonstrate the clinical importance of this property. MATERIALS AND METHODS: Forty-two-, 68- and 94-mm size Wallstents were expanded within cylinders that were 6, 8, 10, and 12 mm in diameter, and their lengths were measured. RESULTS: Progressive stent shortening occurred between diameters of 6 and 10 mm. Extreme shortening occurred at overdilation to 12 mm: At this diameter a 42-mm stent is 24.5 mm long (vs 46 mm at a 10-mm diameter), a 68-mm stent is 40 mm (vs 65 mm), and a 94-mm stent is 64 mm (vs 95 mm). CONCLUSIONS: Specific knowledge of stent lengths at different diameters is required for proper stent choice and accurate deployment. Over-dilation to a 12 mm diameter is useful in correcting excessive stenting and resistant stent narrowings, but it can result in excessive shortening requiring additional stent placement. PMID- 8219560 TI - Interventional radiologic placement of peripherally inserted central catheters. AB - PURPOSE: This study examines the difference in success between bedside insertions of peripherally inserted central catheters (PICCs) performed by clinicians and fluoroscopically assisted insertions by cardiovascular/interventional (CV/I) radiologists. PATIENTS AND MATERIALS: Four hundred four PICCs were inserted in 305 patients, with a mean age of 48 years (range, 8-78 years), who required intermediate and long-term central venous access. One hundred fifty patients underwent bedside insertion, and 155 patients underwent fluoroscopically assisted insertion. Dual- and single-lumen PICC devices were used depending on venous access needs. RESULTS: Central venous access with the PICC device was achieved in 111 (74%) of 150 bedside insertions and in 153 (98.7%) of 155 fluoroscopic insertions. Average PICC dwell time was 72.7 days (range, 2-307 days). Of the 305 patients, 244 (73.4%) completed planned therapy with a single catheter, 54 patients (17.7%) required two PICCs at the same site, 15 patients (4.9%) required three or more PICCs at the same site, and 12 patients (4.0%) required PICC replacement to a different site to complete therapy. Complications with bedside insertions included upper extremity thrombophlebitis (n = 4), entry site infection (n = 6), and PICC shear with migration (n = 2), while complications with fluoroscopic insertions included entry site infection (n = 2). CONCLUSION: Because of the far greater placement success achieved by CV/I radiologists, all PICCs are now inserted fluoroscopically. The devices complete favorably with surgically placed central catheters with regard to service interval, morbidity, and cost. Use of fluoroscopic techniques enables placement of these devices in virtually all patients, even those with seemingly no peripheral veins. PMID- 8219559 TI - Surgery or balloon angioplasty for peripheral vascular disease: a randomized clinical trial. Principal investigators and their Associates of Veterans Administration Cooperative Study Number 199. AB - PURPOSE: Surgical revascularization and angioplasty (PTA) are effective therapies for patients with peripheral arterial disease, but there are no data on long-term survival, limb salvage, and hemodynamic status from a randomized study of such patients. A multicenter, prospective trial compared PTA with bypass surgery (BP) in 263 men who had iliac, femoral, or popliteal artery obstruction. PATIENTS AND METHODS: Lesions in the iliac versus the femoropopliteal artery and rest pain versus claudication were separately randomized to the two treatment interventions. One hundred twenty-six patients underwent BP, 129 patients underwent PTA, and eight patients were not treated for lower extremity ischemia. RESULTS: Three operative deaths occurred in the BP group and none in the PTA group. For the entire study, average annual mortality was higher in the BP group, but survival was not significantly different on life-table analysis (P = .08). Primary success favored BP, while limb salvage favored PTA, but differences were not statistically significant (P = .08 and .35, respectively). Patients with iliac disease or claudication fared better, but there was no statistical difference in response to PTA or BP. CONCLUSION: Patients in both treatment groups had prompt and sustained increases in hemodynamics and quality of life. This study of patients randomly assigned to BP or PTA shows no significant difference in outcomes during a median follow-up of 4 years. PMID- 8219561 TI - Combined transmesenteric and transjugular approach for intrahepatic portosystemic shunt placement. PMID- 8219562 TI - LeVeen shunt insertion with use of a percutaneous translumbar approach to the inferior vena cava. PMID- 8219563 TI - Transcatheter occlusion of Blalock-Taussig shunts: technical options. AB - PURPOSE: This review of findings in children undergoing transcatheter shunt occlusion was carried out to describe and compare the results of four different embolization techniques. PATIENTS AND METHODS: A retrospective review of clinical, radiologic, and cardiac catheterization records was carried out for 18 consecutive pediatric patients referred for Blalock-Taussig shunt occlusion at one institution. Technical aspects included the use of three devices--steel wire/fiber coils, detachable latex balloons, and ductal occlusion devices--and four techniques--direct transarterial placement, transarterial placement with proximal or with distal flow control, and transvenous delivery. RESULTS: Occlusion of the shunt was attempted in 17 patients (mean age, 6.2 years). Shunt occlusion was successful in 14 patients. Embolization of a device into the pulmonary circulation occurred in five patients, and was most frequent with transarterial delivery without flow control or with proximal flow control (in four of six). Transarterial occlusion with distal flow control and transvenous delivery of ductal occluder devices were the most reliable methods of occluding shunts without distal stenosis, with success in eight of nine cases with the former technique and all of three with the latter technique. CONCLUSIONS: Transarterial embolization of Blalock-Taussig shunts carries a risk of device embolization to the pulmonary circulation; this is best avoided by the use of distal flow control or transvenous placement of a ductal occlusion device. PMID- 8219564 TI - Transarterial embolization of vertebral hemangioma. AB - PURPOSE: The authors retrospectively reviewed their 4-year clinical experience to determine the role of transarterial embolization in the treatment of symptomatic vertebral hemangioma. PATIENTS AND METHODS: Eight patients (age range, 12-56 years) underwent a total of 10 embolization procedures; one patient underwent three procedures. The lesions were located between T-5 and L-5, and all patients presented with pain and symptoms referable to the lower extremities. RESULTS: Embolization was technically successful in all patients, and no complications were encountered. Six of eight patients underwent surgery within 48 hours of embolization; four of the six showed significant clinical improvement immediately after surgery and on follow-up (average, 34 months). Two patients did not improve postoperatively. Two patients initially underwent embolization as the sole therapy. The first refused surgery and did not improve clinically; the second underwent two embolization procedures without clinical improvement and eventually underwent a third followed by surgery, which resulted in clinical improvement. All patients were hemodynamically stable during surgery, and blood loss was not problematic in any patient. CONCLUSIONS: Overall, surgery was an effective treatment for symptomatic vertebral hemangioma and the authors conclude that transarterial embolization of vertebral hemangioma is a safe and efficacious adjunctive procedure to such surgery. However, embolization was not as promising as a sole therapeutic modality in this small group of patients. PMID- 8219565 TI - Transcatheter manipulation of asymmetrically opened titanium Greenfield filters. AB - PURPOSE: The problem of asymmetric opening of the modified hook titanium Greenfield inferior vena cava filter necessitating transcatheter manipulation was evaluated in a retrospective study. PATIENTS AND METHODS: Titanium Greenfield filters were placed in 166 patients over a 36-month period. The radiographic reports of all patients were reviewed to identify cases in which the filter failed to open symmetrically after deployment and catheter or wire manipulation of the filter was performed. The reports and angiograms from these patients were reviewed with respect to the circumstances surrounding filter placement and methods to achieve more symmetric opening. RESULTS: Transcatheter manipulation of asymmetrically opened filters was performed in 15 of 166 cases (9%). In 12 of these patients, acceptable and uneventful opening of the filter was achieved with a guide wire, pigtail catheter, or occlusion balloon catheter. In one case manipulation only partly improved orientation of the limbs, while in another case successful manipulation was complicated by distal migration. In the final case, the asymmetric filter covered only part of the lumen of the vena cava despite manipulations and a second filter was placed for optimal caval interruption. No specific cause for incomplete expansion was identified in any case. CONCLUSION: Marked asymmetry in opening of the modified hook titanium Greenfield filter that warrants manipulation occurs infrequently, but recognition and proper management may be important to ensure optimal caval interruption. PMID- 8219566 TI - Deployment problems with the titanium Greenfield filter. AB - PURPOSE: The authors retrospectively reviewed their initial experience with deployment of the modified hook titanium Greenfield filter. PATIENTS AND METHODS: Twenty-three patients underwent filter placements over a 1-year period. Radiographs were obtained immediately after placement to confirm filter position in all cases. Follow-up images were available in 15 patients (65%). RESULTS: Twenty-four filters were placed in 23 patients. Tilting of the filter (> 15 degrees) was evaluated in 22 placements without complications and was present in five (23%). In 17 of 24 placements (71%), distribution of filter legs was poor, with wide gaps between clustered legs. Manipulation of the filter legs with an angiographic catheter resulted in improved distribution in three of six attempts but also resulted in a caudal displacement, which necessitated placement of a second filter. At follow-up (range, 4-16 months; mean, 9 months), three cases of asymptomatic inferior vena caval thrombosis and one recurrent pulmonary embolism were discovered. CONCLUSION: No untoward event resulting from filter placement was demonstrated. Further study and review of the deployment mechanism may be necessary. PMID- 8219567 TI - MR imaging of recurrent cystic adventitial disease of the popliteal artery. PMID- 8219568 TI - Treatment of upper extremity thromboembolic disease with urokinase. PMID- 8219569 TI - Left ventricular perforation due to catheter recoil during aortoperipheral angiography. PMID- 8219570 TI - Prospects for potassium channel activators in the treatment of airways obstruction. PMID- 8219571 TI - A comparative study of the effects of citric acid, capsaicin and resiniferatoxin on the cough challenge in guinea-pig and man. AB - The cough response following inhalation challenge with the sensory nerve irritant resiniferatoxin was compared with that of capsaicin and citric acid in guinea-pig and man. Capsaicin and citric acid gave comparable dose-response curves in the two species. The mean (+/- SEM) concentration producing five coughs in man was 141.3 (1.3) mM (n = 10) for citric acid and 2.8 (1.3) microM (n = 10) for capsaicin. Those for the guinea-pig were 74.1 (1.2) mM (n = 10) for citric acid and 6.0 (2.4) microM (n = 10) for capsaicin. Resiniferatoxin was active at a lower concentration than either citric acid or capsaicin and maximal tolerable cough response was achieved at concentrations of 3 microM (n = 5) in guinea-pig and 300 nM (n = 1) in man. The cough response to resiniferatoxin was greatly prolonged in both guinea-pig and man. Resiniferatoxin, like capsaicin, caused respiratory distress in the guinea-pig which is linked to bronchoconstriction. Resiniferatoxin probably causes cough by stimulation of capsaicin sensitive neurones. PMID- 8219572 TI - Airway response to inhaled methacholine in normal human subjects. AB - The individual airway responsiveness to inhaled, nebulized methacholine (MeCh) was estimated in normal volunteers, measuring specific airway conductance (sGAW). The dose of MeCh was increased logarithmically until a 60-65% reduction from baseline sGAW or an asymptotic approach to a maximal response was attained. The concentration of MeCh that caused a 35% reduction in sGAW (PC35), the dose that caused a 62.5% reduction in sGAW, the slope of the straight, central part of the log-dose-response curve (LDRC), the slope of the straight, initial part of the dose-response curve, the maximal response attainable (Emax) and the dose causing a half-maximal response (ED50) were derived. These parameters were transformed as necessary to attain normality of distribution. Relationships between them were examined by measuring the correlations between their transformed values. The ED50 was taken to represent the least biased estimate of the sensitivity to MeCh. The PC35 was the best practical estimate of sensitivity. The Emax was taken to represent the least biased estimate of the reactivity to MeCh. The slope of the LDRC was the best practical estimate of reactivity. The sensitivity and reactivity varied independently in these normal subjects. Each was also independent of the baseline sGAW. PMID- 8219573 TI - Effects of antidiabetic sulphonylureas, cromakalim and their interaction in guinea-pig isolated tracheal smooth muscle. AB - Glibenclamide, glipizide and glibornuride showed dual effects in guinea-pig isolated trachea. The drugs antagonized the relaxant response to the K+ channel opener cromakalim (order of effectiveness: glibenclamide > glipizide > glibornuride) and at concentrations of 1-1000 microM produced airway smooth muscle relaxation (order of potency: glibenclamide > glipizide = glibornuride). Gliclazide, tolbutamide and chlorpropamide did not antagonize cromakalim nor did the two latter drugs produce tracheal relaxation. The sulphonylureas and cromakalim were compared as airway relaxants against a panel of different spasmogens. The order of tissue responsiveness for the sulphonylureas was: spontaneous tone = LTD4 > PGF2 alpha = histamine = 30 mM K+ > carbachol and for cromakalim: spontaneous tone = LTD4 = PGF2 alpha = histamine > carbachol > 30 mM K+. Glibenclamide, but not cromakalim, relaxed contractions induced by 124 mM K+. Phentolamine and Ba2+, which are reported blockers of ATP-regulated K+ channels, failed to influence sulphonylurea-induced airway smooth muscle relaxation. Glibenclamide reversed tracheal relaxation produced by cromakalim, whereas cromakalim failed to reverse relaxation induced by glibenclamide. The mechanism for the additional property of sulphonylureas to relax airway smooth muscle is unclear, but the results do not support a role for involvement of cromakalim sensitive K+ channels. PMID- 8219574 TI - Effects of levcromakalim and RP52891 on NANCe nerve-mediated changes in pulmonary dynamics evoked by vagal stimulation in the guinea-pig. AB - The effects of the potassium channel activators (KCA) levcromakalim and RP52891 on NANCe nerve-mediated changes in pulmonary dynamics were investigated in the anaesthetized guinea-pig, using a newly-developed respiratory dynamics computer. Levcromakalim (0.025-0.2 mg/kg i.v.) and RP52891 (0.05-0.5 mg/kg i.v.) caused dose-dependent inhibition of NANCe nerve-mediated increases in airways resistance (RAW) and decreases in dynamic compliance (Cdyn). These effects of the KCAs persisted for at least 1 h. Unlike NANCe nerve-mediated responses, equivalent challenges with exogenously-administered substance P (SP; 10-25 micrograms/kg i.v.) and neurokinin A (NKA; 0.5-2.0 micrograms/kg i.v.) tended to produce progressively increasing responses but this effect was not statistically significant. Levcromakalim (0.2 mg/kg i.v.) and RP52891 (0.5 mg/kg i.v.) did not significantly decrease responses to exogenously-administered SP, although NKA induced bronchoconstriction was attenuated. Glibenclamide (25 mg/kg i.v.) partially reversed the NANCe-inhibitory effects of levcromakalim (0.1 mg/kg i.v.) and RP52891 (0.25 mg/kg i.v.) and fully reversed their hypotensive effects. We have shown that levcromakalim and RP52891 inhibit bronchoconstrictor responses to NANCe nerve stimulation. This involves the opening of a glibenclamide-sensitive K(+)-channel and may represent effects at a pre-junctional site on NANCe neurones to reduce transmitter release. PMID- 8219575 TI - Post-synaptic potentiation of vagal contractile responses by neurokinin A. AB - We have studied the effect of neurokinin A (NKA) on tracheal smooth muscle (TSM) contraction caused by administration of acetylcholine (ACh) intra-arterially (ia) into the tracheal circulation, or bilateral stimulation of the vagus nerves, in 26 mongrel dogs. The tracheal contractile response to 10(-7) mol NKA was 3.12 +/- 0.48 g/cm, 6.3 +/- 0.7%AChmax. Plasma histamine concentration was measured in the right atrium at the peak response following administration of NKA. Plasma histamine concentration was 3.33 +/- 2.05 ng/ml after 10(-7) mol NKA (vs. 1.82 +/ 0.54 ng/ml for control, P > 0.10). A frequency-response curve was generated by electrical stimulation of the caudal ends of cut cervical vagi over the range of frequencies 1-20 Hz (constant 30 V) at 15 s intervals 10 min before and 10 min after administration of 10(-8) mol NKA. Substantial augmentation of tracheal contractile responses to 10(-10)-10(-7) mol ia ACh was obtained 10 min after administration of NKA (P < 0.05). Significant potentiation of tracheal contraction to vagal stimulation for 10-20 Hz was also observed after administration of 10(-8) mol NKA (P < 0.05). We have demonstrated a substantial contractile effect of NKA on canine tracheal smooth muscle that is not related to histamine release from respiratory mast cells. We have also demonstrated that NKA causes augmentation of the parasympathetic tracheal contractile response induced by ia administration of ACh and efferent vagus nerve stimulation. These data suggest that potentiation of vagal contractile response by NKA is related to post synaptic activation of the parasympathetic nerves. PMID- 8219576 TI - Do perfused small caliber airways of guinea-pig release an epithelium-dependent relaxing factor? AB - The influence of epithelium removal on the effects of contractile substances on airway responsiveness was investigated on the guinea-pig perfused bronchioles. A gentle rubbing of the luminal surface with a pipe cleaner significantly shifted to the left the concentration-response curves evoked by histamine (3 x 10(-12) 10(-4) M) and acetylcholine (10(-9)-10(-3) M) and decreased the relaxation response to fenoterol (10(-12)-2 x 10(-5) M). In contrast, removal of epithelium did not alter the responses to K+ (4.7 x 10(-3)-1.2 x 10(-1) M), theophylline (10(-8)-10(-2) M), sodium nitroprusside (4 x 10(-10)-4 x 10(-5) M) or papaverine (10(-4) M). In intact preparations treated with indomethacin (10(-5) M), histamine and acetylcholine induced contractions similar to that produced by rubbed tissues whereas relaxation induced by fenoterol was not modified. 10(-5) M tranylcypromine (inhibitor of prostacyclin synthesis) or 10(-6) M L-NAME (NG Nitro-L-Arginine Methyl Ester, a nitric oxide synthesis inhibitor) did not alter any concentration-response curves. Whereas prostaglandin E2 had no effect, prostaglandin E1 (10(-12)-10(-5) M) induced concentration-dependent relaxation, indicating that this prostanoid could be an epithelium-derived relaxing factor. These results suggest that epithelium of small caliber airways could release a cyclooxygenase product, namely a prostanoid, involved in the epithelium-dependent modulation in response to contractile drugs. PMID- 8219577 TI - [Work incapacity in protracted illness--1: Continuation of employment]. AB - The definition of "disablement" of an employee is discussed in detail, first of all from the legal viewpoint of labour legislation in respect of the claim to continuing payment of wages, and secondly from the viewpoint of German compulsory sickness insurance in respect of sickness compensation. The rule of thumb says that the demands made on the employee in respect of performance in connection with the job he had when he fell ill, govern the concept of disablement. If the individual continues to be employed, these demands are decisive and crucial, an exception being if the employee can be transferred to another job in the same plant. PMID- 8219578 TI - [Disability and attitude to preventive measures in patients with acute and chronic diseases of the musculoskeletal system]. AB - The steady increase in the number of patients with musculoskeletal disorders has increased correspondingly the importance of prevention and health promotion in this area. Under the new health reform laws for health promotion we developed a concept of health counselling for persons suffering from acute or chronic musculoskeletal (rheumatic) disorders. In the context of the formative evaluation we surveyed in 1992 the insured persons via a questionnaire classifying them into three different groups of healthy persons and persons with acute and chronic complaints (criterion: accumulated days of work absenteeism). We asked the patients about frequency of rheumatic complaints, subjective and functional injuries. We also investigated the attitudes towards preventive interventions. Parameters like days of work absenteeism and cluster of diagnosis from the database of the health insurance company complete the subjective data. PMID- 8219579 TI - [Psychosocial management in the general hospital--a survey of current status exemplified by Baden-Wurttemberg]. AB - Expert psychosocial care for severely ill people has, time and again, proved both necessary and effective, in particular in the field of oncology. While this fact is reflected by the number of positions allocated to psychosocial care in Paediatric Oncology there remains a grave deficit with regard to adult cancer patients. A survey of all General Hospitals in Baden-Wurttemberg yields concrete figures in respect of the scarcity of positions available in this area. 149 questionnaires were sent out with a response rate of 78.5% (117). Almost a quarter of the hospitals have no social worker on their staff, and trained psychotherapists are almost unknown. In most cases patients are referred to out patient institutions and self-help groups. 94 per cent of the respondees considered an improvement in psychosocial support to be necessary, placing particular emphasis on the training and supervision of hospital personnel. PMID- 8219580 TI - [Screening for toxoplasmosis in pregnancy: more harm than good]. AB - Using data from international literature makes it possible to calculate for Germany benefit and harm of a screening for toxoplasmosis in pregnancy. On the basis of these data harm of such a screening is much greater than benefit. Taking the reported number of congenital toxoplasmosis in Germany as the base for such a calculation of harm and benefit makes the ratio of benefit and harm even worse. PMID- 8219581 TI - [Importation of leprosy into Germany 1981-1992]. AB - 73 cases of leprosy were imported into the Federal Republic of Germany between 1981 and 1992. A large number of imported cases came from Asian countries (32 cases). 61 patients were male, 12 female. 30 patients had the tuberculoid type of leprosy, 29 the lepromatous. From the total of 73 leprosy patients 7 were German nationals. Early diagnosis and efficient treatment play an important role in ensuring a good prognosis. PMID- 8219582 TI - [Epidemiologic pattern of Salmonella enteritidis and Salmonella typhimurium in man--analysis of Salmonella cases in the Brandenburg federal territory]. AB - It is the aim of this study (a study that is part of several investigations suggested and coordinated by the WHO) to highlight the characteristics of transmission of Salmonella in humans. To achieve this, the data collected on the basis of the Federal German Law governing Epidemic Diseases as well as additionally available data (sex, serovar, differentiation between diseased and symptomatic, allocation to the respective place of residence) have been evaluated. In this manner it became possible to determine different patterns of incidence of the presently most frequently occurring salmonella serovars S. enteritidis and S. typhimurium in respect of distribution according to age and sex, as well as the dynamics of distribution and incidence in terms of time. The incidence is particularly remarkable among children, where S. enteritidis is not so frequent as S. typhimurium. There is a distinct trend towards the male sex among children in respect of the infestation. The fact that women are particularly often asymptomatic carriers points to the special nature of the sources and paths of infection. In respect of seasonal dynamics S. typhimurium does not have a specific summer peak, contrary to S. enteritidis, and this too indicates that the mechanisms of transmission or multiplication differ from one another. The study presented here is supplemented by the evaluation of further parameters to support and promote on-target epidemiological investigation into the various problems raised by this and other studies. PMID- 8219583 TI - ["Take it"--a musical by adolescents for adolescents as a new form of AIDS education]. AB - In the spring of 1992, young actors, actresses and musicians presented in Basel for their schoolmates of the 8th and 9th school year a musical on the subject of AIDS. The information content of AIDS prevention was communicated by means of feelings, that means, in an emotional way (and no longer in a mainly cognitive way such as the conventional explanations in the classroom). The performance by youngsters of the same age made what was shown on the stage more credible, and at the same time, contributed to the "otherness" by means of this instruction: not as usual from superiors to inferiors, but on an equal level. This project of a workteam from the Basel Board of Education and the AIDS assistance had a pilot character for the rest of Switzerland and because of this could not draw from experience of similar presentations. Accordingly, there are both several positive as well as negative aspects to the present realisation of the project. PMID- 8219584 TI - [Toxicity of polychlorinated biphenyls (PCB)--indoor air pollution by PCB containing durable elastic sealants]. AB - The widespread use of the persistent and lipophilic polychlorinated biphenyls (PCB) e.g. in electrical engineering, hydraulics and chemistry of the polymers, caused their ubiquitous distribution and accumulation in food chains. Chronic toxicity in humans is known from several incidents of PCB contaminated food. Dose response experiences, however, remain uncertain due to the technical grade of PCB as a complex mixture of about 150 congeners and many impurities, like polychlorinated dibenzodurans. Some information on the toxicity of a few PCB congeners is available from animal experiments. Large differences in enzyme inductive efficacy between the PCB congeners rendered the use of toxicity equivalent factors (related to 2,3,7,8-TCDD, "Seveso-Dioxin") necessary. For risk assessment, the use of "sum of PCB", calculated from questionable determinations of 6 minor toxic congeners, is insufficient. Serious problems arise from evaporation of PCB e.g. in technical rooms of telephone companies (in Germany: Telekom) and generally, from sealing materials in buildings. The German Federal Health Administration, BGA, recommends 300 ng total PCB/m3 indoor air as "precautionary value". Since neither the extreme differences in toxicity of the congeners nor bioaccumulation are taken into account, this recommendation of BGA can not be justified any longer. PMID- 8219585 TI - Fire fighting: how safe are firefighters. PMID- 8219586 TI - ELISA regulatory application: compliance monitoring of simazine and atrazine in California soils. PMID- 8219587 TI - Fluorescent dye and pesticide penetration tested in a computerized spray chamber. Part I. Nonwoven fabrics as barriers. PMID- 8219588 TI - Measuring the genotoxic potential in two drinking water resources of Budapest in Salmonella/microsome system. PMID- 8219589 TI - Cypermethrin in the ambient air and on surfaces of rooms treated for cockroaches. PMID- 8219590 TI - Estrogen as an environmental pollutant. PMID- 8219591 TI - Effects of algae extracts from New York/New Jersey coastline, USA on cultured mammalian cells. PMID- 8219592 TI - Effect of sulphur mustard on mouse skin--an electron microscopic evaluation. PMID- 8219593 TI - Age-dependent accumulation of cadmium and zinc in the liver and kidneys of Norwegian willow ptarmigan. PMID- 8219594 TI - Alterations in bilirubin concentrations during induced aflatoxicosis in rabbits. PMID- 8219595 TI - Phagocytic cells as a contributor to in vivo degradation of alkyl mercury. PMID- 8219596 TI - Selenium induced lipid peroxidation in heart tissues of chick embryos. PMID- 8219597 TI - Target enzyme inhibition by novel thion analogues of monocrotophos: an acute in vivo study in the rat. PMID- 8219598 TI - Cadmium and selenium absorption by Swiss chard grown in potted composted materials. PMID- 8219599 TI - Substrate effects on metal retention and speciation in simulated acid mine wetlands. PMID- 8219600 TI - Wetland retention of lead from a hazardous waste site. PMID- 8219601 TI - Modifying soil lead bioavailability by phosphate addition. PMID- 8219602 TI - Effect of cypermethrin on lactate and succinic dehydrogenase and cytochrome oxidase of snail and fish. PMID- 8219603 TI - Effects of seasonal ambient temperature variations on acute toxicity of chlordane to an air-breathing Indian catfish, Heteropneustes fossilis (Bloch.). PMID- 8219604 TI - Arsenic in Norway lobster (Nephrophs norvegicus L.) from Kvarneric Bay- Northeastern Adriatic. PMID- 8219605 TI - Field studies using the oyster Crassostrea virginica to determine mercury accumulation and depuration rates. PMID- 8219606 TI - Air pollution effects on the guard cells of the injury resistant leaf of Laurus nobilis L. PMID- 8219607 TI - Proposal of a risk score for recurrence in patients with curatively resected gastric cancer. AB - In this study, 168 patients who underwent curative resection for gastric cancer with prognostic serosal invasion [ps(+)] and 150 without prognostic serosal invasion [ps(-)] were analyzed separately to determine the prognostic importance of clinicopathological factors, and identify which patients were at high risk of recurrence. A multivariate analysis of survival time using Cox's proportional hazard model revealed the important prognostic factors to be: Lymph node involvement, the classification of gross appearance, macroscopic serosal invasion, and interstitial connective tissue in the ps(+) group; and lymph node involvement, macroscopic serosal invasion, and venous invasion in the ps(-) group. We proposed a risk score of recurrence based on the results of a further multivariate analysis called Hayashi's Quantification Analysis II, in which recurrence was chosen as an objective variable and the above prognostic factors were chosen as explanatory variables. Eighty-four percent of the patients with a score of 0 or higher in the ps(+) group and 83% of those with a score of +6 or higher in the ps(-) group showed recurrence. Thus, we believe that this score is useful for identifying those patients at high risk of recurrence, who should receive intensive chemotherapy even after curative resection. PMID- 8219608 TI - The role of lymphocyte surface binding sites for wheat germ agglutinin in the negative regulation of cancer patients. AB - The role of lymphocyte surface binding sites for wheat germ agglutinin (WGA) in the negative regulation of cancer patients was investigated. The number of WGA binding sites on the surface of each lymphocyte ranged from 10(7) to 10(8). Fluorescein isothiocyanate (FITC)-conjugated WGA, bound to the majority of peripheral blood lymphocytes (PBL) with two peaks of fluorescent intensity was expressed either dimly or brightly. The increase in lymphocytes brightly expressing WGA fluorescent intensity (WGA bright lymphocytes) significantly correlated with the number of WGA binding sites. The suppression of lymphocyte proliferation mediated by the purified soluble suppressor factor (SSF) significantly correlated with an increase in the WGA bright lymphocyte population (P < 0.05). A significantly greater number of WGA bright lymphocytes in PBL was found in patients with esophageal, gastric, breast, or colon cancer, than in those with benign diseases or in healthy controls. Furthermore, an increase in WGA bright lymphocytes was found in subsets expressing the antigens CD8 dimly or CD16. Thus, it is suggested that the number of WGA binding sites may increase mainly on the surface of effector cells such as NK cells and CD8-positive killer T cells in cancer patients, triggering the negative regulation mediated by SSF. PMID- 8219609 TI - The advantage of primary resection and anastomosis with intraoperative bowel irrigation for obstructing left-sided colorectal carcinoma. AB - Of a total 712 patients with left-sided colorectal cancer, 79 (11%) required emergency surgery due to severe obstruction by tumors. Of these 79 patients, 55 underwent tumor resection and anastomosis. Primary resection and anastomosis with intraoperative bowel irrigation was performed in 44 patients (primary group), while staged resection and anastomosis was performed in only 11 (staged group). In comparing the two groups, there was no significant difference in the rates of curative resection, being 76% versus 90%. However, the primary group demonstrated significantly lower rates of postoperative wound infection (P < 0.001), anastomotic dehiscence (P not equal to 0.05), and postoperative mortality, at 2% versus 18% (P < 0.05). The cumulative survival curve was also better in the primary group (P < 0.05). These favorable results of the primary group were confirmed by analyses which established that no bias of therapeutic backgrounds existed in either of the two groups. Thus, it was concluded that for left-sided obstructing colorectal carcinoma, intraoperative bowel irrigation, followed by primary resection and anastomosis, produces more advantageous results. PMID- 8219610 TI - Induction of discriminant function concerning postoperative local recurrence or distant metastasis in 589 patients with differentiated thyroid cancer. AB - For the purpose of predicting postoperative local recurrence and/or distant metastasis in differentiated thyroid cancer, a discriminant analysis was done. To assess the reliability of this method and the induced function, simulation was done by using random samples under various conditions. Simulation revealed that the results obtained by this method were relatively stable. The discriminant functions Z1 and Z2 were induced, which are required at many hospitals. If the ratio of recurrence is less than 1:8 in a hospital, function Z1 should be applied. If the ratio is 1:10, function Z2 should be applied. Z1 = -(sex x 2.104) + (age x 0.032) - (diameter of tumor x 0.033)-(site of tumor x 0.871) - (histology x 0.393) + 0.249 (discriminant boundary 0.451) Z2 = -(sex x 1.967) + (age x 0.018) + (diameter of tumor x 0.025) - (site of tumor x 0.646) + (histology x 0.014) - (local invasion x 0.840) - (lymph node metastasis x 0.009) + (operation x 0.364) - (lymph node dissection x 0.235) + 1.058 (discriminant boundary 0.400). In an internal check, sensitivity was 78%, specificity 64%; and false-negative rate 5%. In an external check, sensitivity was 68%, specificity 93%, and false-negative rate 9%. In the actual application to hospitals, sensitivity was 58% to 100%, specificity 47% to 63%, and false-negative rate 0% to 16%. In clinical usage, a high sensitivity and low false-negative rate are required. These results fulfilled this condition. PMID- 8219611 TI - Abdominal wall lifting with subcutaneous wiring: an experience of 50 cases of laparoscopic cholecystectomy without pneumoperitoneum. AB - Abdominal wall lifting is a method to produce operative space between the anterior abdominal wall and the intra-abdominal organs during laparoscopic surgery. We devised a hanger lifting procedure for the anterior abdominal wall to avoid complications as well as reduce the costs related to the pneumoperitoneum. In our series, we performed 50 cases of laparoscopic cholecystectomy with this abdominal wall-lifting procedure. Though at the beginning we performed laparoscopic cholecystectomy by the pneumoperitoneum, we discarded the insufflator for this operation since starting the new procedure. There was no incidence of conversion to pneumoperitoneum and a fairly good operative view was achieved enabling a smooth laparoscopic cholecystectomy. PMID- 8219612 TI - A successful liver metastasis model in mice with neuraminidase treated colon 26. AB - The aim of this study was to establish a reproducible and quantitative liver metastasis model in mice. The in vitro colon 26 (C-26) cultured cell line was initially taken from an in vivo transplantable C-26 adenocarcinoma tumor mass using the standard enzymatic treatments, collagenase and DNAse. In vitro cultured cells x 10(4) were introduced into the portal vein of syngeneic BALB/c mice to induce liver metastases and, 3 weeks later metastatic foci were found in approximately 50% to 70% of the mice. In contrast, C-26 cells desialylated by neuraminidase (Nase) treatment greatly increased the incidence of hepatic metastases with countable hepatic colonies being found in all mice (100%). This result seems to be related to the liver-characteristic D-galactose receptors, since pre-injection with an excess amount of galactocerebroside completely prevented tumor colonization in the liver. Thus, although we cannot disregard the involvement of other adhesion molecules in this system as yet, our experimental model may become a useful tool for the analysis of hepatic metastases from colon cancer in the future. PMID- 8219613 TI - The surgeon's technical skill in suturing: an analysis of the actual suture tracks. AB - Ideal suturing was defined as advancing a needle along its curvature (needle circle) to minimize tissue trauma, while placing the suture with its intended span and tissue bite in the expected place. Actual suture tracks were analyzed to find the keys to produce such suturing. Correspondence of those tracks to the ideal track was then determined by the span, the initial needle angle (IA) into the tissue, and the center of the needle circle. Eight surgeons with 4-7 years of experience produced 22 ideal sutures in two types of tissue simulants: The entrance and exit points of the needle were level in flat suturing, while the entrance point was slanted 45 degrees for slant saturing. The correspondence was better with slant suturing than flat suturing (P < 0.01). The IA in flat suturing was 49.0 +/- 2.0 (mean +/- SE) degrees versus 33.0 for ideal suturing (P < 0.01), while that in slant suturing was 35.5 +/- 1.9 (P: ns). In conclusion, the IA was the key to good results, and was optimized in slant suturing, which was instinctively utilized in practice by using forceps. The forceps avoided a derangement of suturing stemming from the configuration of the needle employed and from the range of motion of the surgeon's arm (human engineering), while satisfying the surgeons inclination to take a large IA. PMID- 8219614 TI - Intractable chest pain in a patient whose postpneumonectomy space was managed with sulfur hexafluoride. AB - A 50-year-old man who had undergone right pneumonectomy 1 year previously was referred to our department following the sudden onset of severe chest pain. Since the operation, his postpneumonectomy space had been managed with sulfur hexafluoride. On admission, the pressure in the postpneumonectomy space was found to be more than +60 cmH2O. The chest pain was relieved after the sulfur hexafluoride had been drained and the pressure released. Thus, it is advisable to inject sulfur hexafluoride stepwise into the postpneumonectomy space of patients with long-standing fluid accumulation. PMID- 8219615 TI - A case report of gastric cancer associated with sarcoid reactions in the regional lymph nodes and liver. AB - Epithelioid cell granulomas identical to those of systemic sarcoidosis are occasionally observed within malignant neoplasms, particularly in the lymphatics draining a primary tumor. These histologic changes have been termed sarcoid reactions and are easily confused with systemic sarcoidosis. This report describes an extremely rare case of gastric cancer accompanied by sarcoid reactions in the regional lymph nodes and liver parenchyma near a tumor metastasis. A 63-year-old woman with advanced gastric cancer was treated by subtotal gastrectomy with dissection of the regional lymph nodes and local excision of the liver tissue involved by metastasis. Microscopic examination of the resected lymph nodes and liver disclosed the presence of sarcoid-like granulomas. The absence of any clinical manifestations and the negative results of the Kveim test, chest radiograph, and laboratory tests, including that for the serum angiotensin converting enzyme excluded the possibility of systemic sarcoidosis. The presence of a sarcoid reaction in the liver parenchyma adjacent to a metastasis has never been reported previously. PMID- 8219616 TI - Familial neurilemmomatosis: report of a case. AB - We report herein a case of familial neurilemmomatosis seen in a 16-year-old girl and her 38-year-old mother. The girl presented to us with an intrathoracic vagal neurilemmoma, as well as neurilemmomas on the right fifth intercostal nerve and in the serratus anterior muscle. Two years after these tumors were resected, bilateral acoustic neuromas and multiple brain stem tumors appeared. Her mother was being treated simultaneously at another hospital for multiple neurilemmomas, including bilateral acoustic neurilemmomas, suggesting the possibility that neurilemmomatosis is an autosomal dominantly inherited disorder. PMID- 8219617 TI - Curatively resected primary malignant melanoma of the esophagus: report of a case. AB - We report herein a rare case of primary esophageal malignant melanoma in a 49 year-old Japanese woman who presented with a 3-week history of dysphagia. Esophagogram and esophagoscopy demonstrated a polypoid tumor in the upper to mid thoracic portion of the esophagus, and a radical subtotal esophagectomy was performed through a right thoracotomy. Histological and immunohistochemical studies proved this tumor to be a primary esophageal malignant melanoma. She received no postoperative adjuvant therapy and no signs of recurrence have been clinically observed for the 22 months since her operation. PMID- 8219618 TI - Cronkhite-Canada syndrome associated with colon cancer: report of a case. AB - A 68-year-old man with the clinical features of Cronkhite-Canada syndrome developed cancer of the ascending colon. Although Cronkhite-Canada syndrome has always been considered a benign condition, it may be a premalignant disorder, as suggested by the clinical course of the patient whose case is described herein. PMID- 8219619 TI - A possible prototype of multifocal recurrence after liver resection of hepatocellular carcinoma: report of a case. AB - The clinical course of a 68-year-old male with HCC is herein reported. In addition to two tumor nodules detected preoperatively, the resected surgical specimen disclosed macroscopically invisible tumor-cell clusters as well as intrahepatic metastatic foci. These clusters had no clear border and were more basophilic with small-sized cells, high cellularity, and a higher nuclear/cytoplasm ratio, which was suggestive of early HCC with a form of de novo occurrence. The postoperative course, characterized by an early recurrence of small nodules in the remnant liver suggested the presence of a similar invisible tumor mixture at the time of operation. This case can thus be regarded as a prototype of the multifocal recurrence type. PMID- 8219620 TI - Heterotopic autotransplantation of the pancreas segment after pylorus-preserving total pancreatectomy: a case report of successful surgical treatment for chronic pancreatitis. AB - A 38-year-old man who had suffered for 5 years from persistent abdominal pain caused by alcoholic chronic pancreatitis, presented with diffuse calcification of the entire pancreas with cystic formation of the pancreatic head. After a pylorus preserving total pancreatectomy, the pancreatic head, including the cyst, was removed extracorporeally by bench surgery, and the remaining segment of the body and tail autotransplanted heterotopically to the iliac vessels with a pancreaticojejunostomy. Total resolution of the pain was achieved postoperatively, and dietary intake has been satisfactory. Both endocrine and exocrine pancreatic functions have been well preserved, and no insulin has been needed. Three months after his operation, the patient has returned to leading a normal life. PMID- 8219621 TI - Sequential changes in the cell mediators of peritoneal and wound fluids after surgery. AB - The concentrations of cell mediators in the peritoneal and wound fluids of patients who underwent abdominal surgery or mastectomy were determined sequentially and compared with the concomitant changes in blood components. The level of interleukin-6 (IL-6) in the peritoneal and wound fluids was significantly higher than the plasma level after gastrectomy (P < 0.001), cholecystectomy (P < 0.05), and mastectomy (P < 0.05), although the level of plasma IL-6 was also higher postoperatively than before surgery (P < 0.001, P < 0.05). Significantly higher levels of tumor necrosis factor-alpha were detected in the peritoneal and wound fluids (P < 0.01, P < 0.05, respectively) after surgery despite its absence in plasma. A platelet-specific protein and a protein specific for fibroblasts were also measured. Thus, mediators derived from various cells were shown to be present in human peritoneal and wound fluids, indicating that the local production of these mediators plays an important role in the process of tissue repair. PMID- 8219622 TI - AHNA certificate program in holistic nursing courses. AHNA certificate program in healing touch courses. PMID- 8219623 TI - Healing images. PMID- 8219624 TI - [Pathology of the vitreous body. Primary aspects and principles]. AB - Due to its simple structure, the vitreous body exhibits only a limited spectrum of pathological reactions. This structure undergoes age-related changes and degeneration throughout life. Modification in the relation between collagen and hyaluronic acid causes condensation of the vitreous fibrils, forming tractus, membranellae, and strands next to formations of clefts, lacunae, and detachments. Diseases of the adjacent tissues influence these degenerations qualitatively as well as quantitatively. According to its current condition, the vitreous body can influence the course and extent of diseases of adjacent tissues, its own structures acting as barriers or guiding formations for cells and tissues or as tracting "tendons". These basic principles are illustrated with examples from the particular pathology of the vitreous. PMID- 8219625 TI - [What is the etiology of diabetic retinopathy?]. AB - Recent experimental and clinical investigations suggest several pathogenetic mechanisms for diabetic retinopathy. The pathogenesis of diabetic retinopathy can best be understood by a concerted action of biochemical, hemodynamic and endocrine or cytokinetic factors. Biochemical factors such as nonenzymatic glycosylation and induction of the aldose reductase pathway seem to be of importance for the genesis of nonproliferative diabetic retinopathy, characterized by pericyte loss, basal membrane thickening and formation of microaneurysms. The development of the proliferative form, characterized by ocular neovascularization, is the response to chronic hypoxia and is probably due to the angiogenetic influence of hormones and growth factors. The most important therapeutic approach is strict control of hyperglycemia. PMID- 8219626 TI - [Results of pars plana vitrectomy in chronic uveitis in childhood]. AB - During 1986-1991 vitreous surgery was performed in 5 girls and 8 boys (age range 2-15 years) with chronic uveitis. In 6 cases a combined lensectomy-vitrectomy was performed because cataract was present, so that the results generally refer to 19 eyes. We found a low rate of postoperative complications. During a follow-up period of 6 months to 5 years (average 2 years and 1 month), 12 of the 19 eyes showed a significant visual improvement. Preoperatively, 8 eyes were found to be affected by cystoid macular edema; in 7 of these cases remarkable regression of the edema was observed after surgery. In two-thirds of cases the intensity of the inflammation decreased, so that the dose of corticosteroids could be reduced postoperatively. Our results suggest that vitrectomy for chronic uveitis in children is a relatively safe and successful treatment. In order to prevent irreversible complications and amblyopia surgery should be performed in an early stage of the disease. PMID- 8219627 TI - [Pupillary dilatation with Eckardt iris retraction sutures within the scope of vitreoretinal surgery. A follow-up study]. AB - In cases of complicated vitreoretinal surgery, maximal mydriasis is necessary. Preexisting or intraoperatively occurring miosis in aphakic eyes can be remedied by the iris suture by Eckardt. In our hospital, the iris suture technique was carried out in 31 cases. The postoperative situation depends on the extent of retraction of the iris sutures and the general course of the disease. At maximal retraction, the iris is forced against the ciliary body, causing persisting synechias; therefore, to us it seems important to separate all synechias after opening the iris sutures. The formation of anterior loops is also possible. Thus, it is essential to release the endangered segments behind the ciliary body and at the base of the vitreous body from tractive elements immediately after opening the iris sutures. Based on our present experience, we think non-maximal retraction of the iris is desirable. It offers enough view of the fundus and reduces the complications mentioned above. PMID- 8219628 TI - [Clinical and histologic findings after several weeks of intraocular tamponade with perfluorodecalin]. AB - Perfluorocarbon residues sometimes remain in the eye following vitreoretinal procedures employing liquid perfluorocarbons. According to the literature, one or two droplets do not appear to damage the ocular tissue. The question of whether this also applies to larger volumes was investigated in two eyes of two patients. Both eyes were injected with perfluorodecalin for removal of luxated lens in two patients. In one patient approximately 3 ml perfluorodecalin remained in the eye for 3 months postoperatively, in the other patient approximately 4 ml for 4 months. The eye of the first patient developed an inoperable complicated retinal detachment. The second eye developed a secondary glaucoma requiring additional cyclocryocoagulation after removal of the perfluorocarbon. Histological examination of excised retinal tissue revealed extensive destruction of the normal architecture with a marked reduction in the number of cells in the nuclear layers. It remains unclear whether these findings can be attributed to toxic or mechanical damage. PMID- 8219629 TI - [Vitrectomy in oculocerebral non-Hodgkin's lymphoma]. AB - Ocular non-Hodgkin lymphoma (NHL) is thought to be a rare intraocular tumor; the clinical diagnosis, however, is difficult, and ocular NHL might occur more frequently than we thought. Vitrectomy is essential for establishing the diagnosis. During the last 6 years, we performed vitrectomies for ocular NHL in seven eyes of four patients. We report on the visual outcome and cytological findings. In three patients, we suspected the oculocerebral form of the disease; one patient suffered from a systemic lymphoma. The mean observation time was 19 months (5-30 months). In one patient, we failed to examine the vitreous fluid; this patient has since died. The other three patients underwent radiation treatment and/or chemotherapy; they are alive, and no recurrence of the NHL has since occurred. In all five cases in which cytological examination of the vitreous fluid was performed, we were able to establish the diagnosis of NHL on the first attempt. This accuracy is due to rapid and careful processing by the cytologist. Vision improved considerably in most cases. In only one eye with heavy retinal infiltration could vision not be restored. Secondary cataract extraction was necessary in five cases; otherwise, vision remained stable. We conclude that vitrectomy has to be done early in atypical vitreous "inflammations". Immediate processing and cytological examination of the vitreous fluid establishes the diagnosis of NHL and permits accurate radiation or chemotherapy. Early vitrectomy is greatly beneficial not only for visual rehabilitation but maybe even for a longer life expectancy. PMID- 8219630 TI - [Substance analytic studies of the effectiveness of laser coagulation in diabetic retinopathy]. AB - An order to optimize photocoagulation in diabetic retinopathy, it is necessary to have objective criteria concerning substance-specific fundus changes like blood, melanin, xanthophyl, cytochrome aa3, and light scattering. By means of fundus reflectometry macular reflectance spectra can be measured and are different in normals and in diabetics before or after treatment. If logarithmic difference spectra are used only pathological alterations or changes caused by the coagulation are demonstrable. These difference spectra can be approximated by a linear model function containing the extinction spectra of the substances mentioned above and a term for light scattering. Spectra deconvolution delivers coefficients, describing differences in the substance concentrations between diabetics before and after treatment and age-matched normals. When we examined these coefficients, we found that neither their behavior in diabetic retinopathy nor their reaction to photocoagulation is unique. Thus, it might be possible to obtain references to patient-specific adapted coagulation by deconvolution of the macular reflectance spectra measured before treatment. Classification of the patients in specific types of reaction, according to the shape of the logarithmic difference spectra or the results of the spectra deconvolution, could be a step in deciding on the success of the therapy on a case-to-case basis. PMID- 8219631 TI - [Comparative use of diode and argon laser for panretinal photocoagulation in diabetic retinopathy]. AB - The recently introduced semiconductor diode laser is portable, more compact, and cheaper to maintain than other laser systems. It is unclear whether its wavelength characteristics in the near infrared (810 nm) lead to different clinical results of retinal photocoagulation. In a prospective study ten diabetics (3 type I and 7 type II) ranging in age from 26 to 72 years with bilateral proliferative or severe nonproliferative diabetic retinopathy and visual acuity better than 6/18 in both eyes underwent panretinal photocoagulation. One eye was treated with the diode laser, the fellow eye with argon green (514 nm). Follow-up was documented by best-corrected visual acuity, fundus photography and fluorescein angiography. Mean duration of follow-up was 12 months. In neither group was there a significant difference in the response of retinopathy and neovascularization to the treatment, or in the course of visual acuity. Fluorescein angiography revealed the more profound effects of the diode laser in the choroid. Compared to argon laser treatment, patients found diode laser treatment more painful, but appreciated the absence of bright flashes during therapy. Photocoagulation for diabetic retinopathy using the diode laser was as effective as using the argon system in this initial pilot study. PMID- 8219632 TI - [Do scars grow despite successful laser coagulation of subretinal neovascularization?]. AB - After successful laser coagulation of subretinal neovascularization, we examined 9 patients to see if laser scar growth (which can be expected according to the literature) is accompanied by an increase in associated scotoma. We used a specially designed visual field program. Laser scars had grown by 23% 107 days after therapy and by 32% after 409 days. The changes in our patients were at the lower range of the data reported in the literature. The increase in the laser scar was statistically significant in just one patient. Mean sensitivity and two further parameters for describing visual fields, which we introduced, all hinted at an improvement in the central visual field, although the laser scars had grown. The mean sensitivity increased by 4.9% and 7.5% after 107 and 409 days, respectively. PMID- 8219633 TI - [Proliferative vitreoretinopathy. On the significance of protein transfer through the blood-retina barrier]. AB - In several studies, unphysiologically high concentrations of different proteins have been measured in the vitreous of patients with proliferative vitreoretinopathy (PVR). It has not yet been determined whether these high values result from the alteration of the blood-retina barrier (BRB) or whether the proteins are produced intraocularly. In the present study we measured the concentrations of IgG and complement factor C4 in vitreous aspirates and plasma samples from patients with PVR (n = 15). We calculated an IgG and C4 index analogous to the IgG index in routine cerebrospinal fluid chemistry, which is used to estimate the rate of intrathecal IgG synthesis. Comparison of the C4 index revealed no significant difference between patients and controls. Although a higher IgG index was demonstrated in pathologic vitreous, no intravitreal cells that are able to synthesize IgG have been found. These findings suggest that high levels of IgG and C4 are related to an elevated transfer at the disrupted BRB. PMID- 8219634 TI - [Technique of selective, controlled retinal fibrinolysis in a model]. AB - By microcatheterization of the ophthalmic artery it was possible to test a controlled retinal fibrinolysis in the rabbit. Heparin, tolazoline and urokinase were applied through the microcatheter. By continuous administration of highly diluted fluorescein (0.1%), on-line control of the therapeutic effects was available. Treatment was carried out in cycles of enforced perfusion. In 12 main vessel occlusions the rates of flow could nearly be normalized after mobilization of thrombi by combined emergency therapy. An average of 14 cycles of treatment was necessary. The time needed was 40-60 min. With this technique drug therapies of ocular circulation disturbances are testable and controlled emergency treatment of the eye begins to become feasible. PMID- 8219635 TI - [Mitral valve prolapse. A possible cause of retinal vascular occlusion in young patients]. AB - Retinal vessel occlusion in the elderly is considered to be of arteriosclerotic etiology, but in young patients the reasons for retinal vessel occlusions are manifold and much more obscure. We report on five patients under the age of 45 years who had retinal artery occlusion or retinal vein obstruction. A detailed general investigation revealed nothing but an identical cardiac abnormality in all five cases: mitral valve prolapse (MVP). A potential explanation for the coincidence of retinal vessel occlusion and MVP might be local hyperaggregability of platelets generated by the prolapsing mitral valve. In conclusion, to prevent retinal vessel occlusion from recurring in patients with proven MVP, medication containing platelet aggregation inhibitors should be given. PMID- 8219636 TI - [Retinal hemodynamics in patients with arterial hypertension]. AB - Arterial hypertension is a risk factor for the development of retinal, cerebral and renal microangiopathy. Therefore, a prospective study was started to investigate the progression of retinal microangiopathy in hypertensive patients. Initially, 254 patients were examined in a cross-sectional study. Following an ophthalmological examination, retinal hemodynamics were quantified by means of video-fluorescence angiography. Moreover, blood fluidity (hematocrit, plasma viscosity and erythrocyte aggregation) was analyzed. The severity of the retinal changes was defined according to the Neubauer classification. One hundred (40%) patients showed retinal changes corresponding to stage I; 133 (52%) were classified as stage II. Hypertensive retinopathy (stage III and IV) was encountered in 20 (8%) patients. Arm-retina time was significant prolonged among the hypertensive patients compared with a control group. Arteriovenous passage time showed no significant differences between hypertensive patients and reference values. Plasma viscosity was significantly increased in hypertensive patients and showed a significant increase with progression of the retinal changes. Hematocrit and erythrocyte aggregation were normal among the patients studied. The present findings show an alteration in blood fluidity among hypertensive patients, whereas retinal microcirculation showed no significant disturbances. Follow-up studies are planned to assess the development of retinal microcirculatory changes among hypertensive patients. PMID- 8219637 TI - [Serum lipids and vitamins in senile macular degeneration]. AB - P6e correlations between serum cholesterol, triglycerides and lipoproteins and serum vitamins A and E were tested in patients with age-related macular degeneration (AMD). Patients diagnosed as having "senile" macular degeneration who were not receiving medical treatment that would interfere with lipid or vitamin metabolism consecutively underwent-fundus photography and fluorescein angiography in a 6-month period. Cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), vitamin A and E were assayed using conventional methods (enzymatic and high-performance liquid chromatography). Sixty-four angiographies from 64 patients were evaluated. The clinical diagnosis was: "hard" drusen (n = 5), geographic atrophy (25), "soft" drusen (10), subretinal neovascularization and disciform scar (24). The percentage of pathological data was calculated: HDL, 89%; cholesterol, 84%; vitamin A, 75%, LDL, 66%; Vitamin E, 33%; triglycerides, 23%. The data differed somewhat between groups. The high prevalence of hypercholesterolemia in older age groups [3, 34] prevents cholesterol from being identified as a risk factor for AMD. Elevated levels of atherogenic LDL and reduced vitamin A are discussed versus "protective" HDL and vitamin E. In many of the AMD cases described, the cardiovascular risks of dyslipoproteinemia demand adequate therapy. PMID- 8219638 TI - [Resorption of post-traumatic cilio-choroid (supra-choroid, sub-scleral) hematoma. A histopathologic study]. AB - The healing process of ciliochoroidal (suprachoroidal, subscleral) hematomas was studied histopathologically in 75 eyes enucleated between 1 and 42 days following a traumatic incident. The ciliochoroidal hematomas occur from ruptured vortex veins or ciliary blood vessels located in the suprachoroidal (subscleral) space. Detached ciliary blood vessels and nerves form a network within the hematoma. In early stages there is little fibrin formation and no signs of coagulation are visible. Then hyperemia of uveal blood vessels develops, followed by a perivascular accumulation of polymorphonuclear leukocytes and lymphocytes with edema. About 11 days after the traumatic event a thin mesenchymal cell layer covers the outside of the hematoma, which at this stage shows some hemolysis. After 2 weeks proteinaceous exudate with lipid vacuoles is present and fibroblastic activity is increased on the uveal side of the hematoma and along the septating blood vessels and nerves. After 3 weeks the outer uvea is impregnated by phagocytic cells containing hemosiderin (hemosiderophages). Twenty eight days after trauma the fibrous lining of the hematoma has increased. In principle a seroma with septum formation has evolved from the suprachoroidal hematoma. This is regarded as a complicated healing process, which hinders surgical drainage of long-standing post-traumatic hemorrhagic ciliochoroidal detachment and therapy of post-traumatic ocular hypotony. PMID- 8219639 TI - [DNA flow cytometry of malignant melanoma of the choroid]. AB - Thirty-five choroidal melanomas were analyzed by flow cytometry. DNA euploidy, aneuploidy and polyploidy were found in approximately 54, approximately 46, and approximately 20% of the tumors, respectively. No correlation between histological type and ploidy was found. The synthesis phase was irregular in approximately 25 and approximately 38% of the spindle and the mixed cell melanomas, respectively. The G2M peak was broadened in approximately 50% and in approximately 23% of the spindle and the mixed cell melanomas. About 20% of the malignant melanomas were highly proliferative. In 25% of the melanomas chemotherapy seemed to be useful. PMID- 8219640 TI - [Sensitivity of immunoscintigraphy in malignant melanoma of the choroid]. AB - Between June, 1988 and May, 1991 30 patients with clinically suspected malignant melanoma were examined in succession by means of immunoscintigraphy and the 225.28 S antibody (tagged with Tc-99m). Retrospectively, the results showed a sensitivity of over 70% by SPECT examination. Positive accumulation of the antibody within the suspected melanoma gives reason to believe that this degree of accuracy can be improved by comparative application of unspecific, radioactively tagged proteins. In the absence of accumulation within clinically, and in particular echographically, confirmed malignant melanoma treatment should be performed. PMID- 8219641 TI - [Vitreoretinal changes in siblings of two patients with Stickler syndrome. Study of two families]. AB - In 1965 Stickler described a pedigree combining ocular, facial, palatal and skeletal changes. The ocular findings comprise vitreoretinal changes, tears, retinal detachment, myopia and subcapsular cataract. We investigated eight siblings in two families with Stickler syndrome, two of them with a retinal detachment. In two members we observed subcapsular cataract, in four members an optically empty vitreous containing sparse transvitreal strands and sheets of condensed vitreous behind the lens; in the eyes of four emmetropic members with normal visual function large oral bays and large dental processes were found which extended much more posterior to the equator with localized depigmentation, erosions and small tears in the affected area. Similar changes could be observed in the second eye of one patient with a retinal detachment due to a giant tear. The changes of the peripheral retinal pigment epithelium in addition to the affected vitreoretinal base and vitreoretinal adhesions are responsible for the development of erosions, small tears, or even giant tears. Minimal changes as observed in the second eye of our patients with retinal detachment, or in the fundus of other family members, seem to be precursors of retinal detachment. Changes in the second eye of retinal detachment or in the retina of "unaffected" family members without retinal detachment or other associated symptoms of Stickler syndrome should be evaluated regularly and, if necessary, treated by laser, cryotherapy or even an encircling procedure. PMID- 8219642 TI - [Ocular carbon dioxide reactivity in retinitis pigmentosa. Perimetry results]. AB - Ocular pulse volumes (POV) measured by oculo-oscillo-dynamography were markedly reduced in Retinopathia pigmentosa (R.P.) patients (n = 52) compared to healthy subjects (n = 107). During breathing increased carbon dioxide concentrations (6.5%) POV returned nearly to normal values [15,17]. In an attempt to evaluate the effects of increased inspiratory carbon dioxide concentrations on the visual field in R.P. patients the following study was performed. In 24 patients (24 right eyes, 23 left eyes) suffering from a clinically and electrophysiologically confirmed R.P. kinetic visual field testing was performed. After a standardized kinetic Goldmann-perimetry (V/4; III/4; I/4; I/3; I/2; I/1) during breathing normal air the visual field testing was repeated during breathing increased carbon dioxide concentrations (6.5%). The visual field area was measured with a planimeter (Hewlett Packard 9874 A Digitalizer) separately for each isopter. For a better comparison of the results the change in the visual field was expressed as a percentage value of the initial visual field area of each isopter. During breathing increased carbon dioxide concentrations the visual field area improved, expressed as the median of all isopters, by x = 29% in 24 right eyes and by x = 18% in 23 left eyes. The results presented suggest that breathing of increased carbon dioxide concentrations improve ocular hemodynamics and furthermore have a beneficial effect on the remaining visual field area in R.P. patients. PMID- 8219643 TI - [Color vision defect. A early sign of Sorsby retinal dystrophy?]. AB - In 34 asymptomatic patients from three families at 50% risk of developing Sorsby's fundus dystrophy, colour contrast sensitivity was measured. In 16 the thresholds--mainly of the tritan axis--were raised above the normal values. It is concluded that testing of colour vision is useful in detecting the abnormal genotype. Raised colour contrast sensitivity was not observed before the first fundus or fluorescein angiographic changes in two of the families, while the colour defect occurred in the absence of ophthalmoscopic abnormality in the third family. Therefore, our results support the clinical suggestion that Sorsby's fundus dystrophy is more than one disease. PMID- 8219644 TI - [Carcinoid tumor of the lung. An unusual form of ocular metastasis]. AB - Carcinoid tumors are slowly and locally invasive growing neoplasms. Their main localization is in the ileum or in organs derived from the embryonic foregut, i.e. bronchus, stomach, pancreas and thyroid. The low rate of metastatic manifestation of about 10% indicates their potential malignancy. The endocrine effects vary. We describe the case of a 30-year-old female patient, who had had a carcinoid tumor of the bronchus with infiltration of a hilar lymph node, which had been resected two years previously. The postoperative course was marked by an increased level of urine 5-hydroxyindolacetic acid (5-HIAA). Finally, the patient complained a 4-month history of recurrent episodes of refractory conjunctival hyperemia, visual loss and visual field defects in both eyes. Examination revealed bilateral multiple choroidal masses associated with retinal detachment. As various authors have reported, carcinoid tumor metastases to the eye are extremely rare. Diagnostic approaches and therapeutic considerations are described. Ultrasonic examination of the choroidal lesion, applying standardized A-scan echography at tissue sensitivity, showed solid tissue masses and bilateral circumscribed exudative retinal detachment. The tumor was characterized by medium to high reflectivity and slight sound attenuation. The internal structure showed less irregularity than is usually seen in metastases. PMID- 8219645 TI - [Proliferation markers, enzyme markers and oncogene expression profile of intraocular melanoma]. AB - In this study 9 uveal melanomas, 1 iris melanoma and 1 conjunctival melanoma were evaluated for their proliferation activity with antibodies to KI67 protein. In addition, the distribution of glutathion-S transferase (alkaline and acid isoforms) and lysosomal cathepsin D protease was demonstrated immunohistochemically. The expression of the oncoproteins c-neu (internal and external domaine) and ras (mutated and non-mutated isoform) were also analyzed with specific monoclonal antibodies. In the case of the metastasing melanoma significant Ki67 protein expression and marked expression of the oncoproteins ras p21 and pan ras were obvious. All other melanomas showed less proliferation and enzymatic activity with a moderate expression pattern for oncoproteins. Regarding the results of the proliferation and enzymatic markers, the tumors were heterogeneous; single cells or clusters may play a role in the prognosis of the tumor if there is an intense immunohistochemical reaction. The influence of histomorphological criteria, e.g., cell subtype, seems to be minor compared to immunohistochemical criteria. PMID- 8219646 TI - [Erroneous vision determination and quantitative effects]. AB - The experimentally determined psychometric function for Landolt rings (8 orientations, 183 eyes) is used to calculate the statistics of visual acuity results according to DIN 58,220 and their bias due to deviations from DIN 58,220. Test procedure fulfilling DIN 58,220, criterion 3/5: With a second test the first result is reproduced in 33.7%. In 47% the difference is 1 step, in 16.2% 2 steps, and in 2.8% 3 steps. Selecting the highest acuity value out of several tests yields a bias of +0.44 steps (2 tests), +0.66 steps (3), +0.81 steps (4 tests). Deviations from DIN 58,220, criterion 3/5: Linearly instead of log-scaled optotypes: above acuity 0.2 the effect is minimal (< 0.1 steps). For acuity 0.1 the bias is -0.9 steps. Old criterion 3/4: bias -0.55 steps; Repetition of a failed optotype: bias +1.11; Repetition of a failed acuity step: +0.61; Continued test despite fulfilled break condition: bias +0.3 steps; Weakened criterion of 2/5: bias +0.89 steps. CONCLUSIONS: Visual acuity values can contain considerable errors. There is a need for more effective algorithms and an unbiased investigator. The solution is programmed automatic testing on a computer screen. PMID- 8219647 TI - [Magnetic intraocular foreign body in the posterior eye segment. Current treatment concepts]. PMID- 8219648 TI - Biomedical and clinical aspects of coenzyme Q. PMID- 8219649 TI - Heinrich Wieland-Prize Lecture. Laudation to L.D. Bergelson. PMID- 8219650 TI - Gangliosides and antitumor immunity. AB - To elucidate the possible influence on the host's immune defense of circulating gangliosides released from tumor cells, the effects of exogeneous gangliosides on the activities of some lymphocyte subpopulations were examined. The mono- and disialyllactosylceramides GM3 and GD3, which frequently are present in elevated amounts in sera of tumor-bearing hosts, were found to inhibit strongly the cytotoxicity of natural killer cells, to stimulate T-suppressor activity of peripheral blood lymphocytes, and to inhibit their phytohemagglutinin-induced blast transformation. All these effects may be linked to the ability of gangliosides to modulate the arachidonic acid cascade in lymphoid cells, which for the first time was demonstrated in the course of our studies. Possible mechanisms underlying the immunomodulatory effects of serum gangliosides as well as their role in the escape of tumor cells from immune surveillance and inhibition of the hosts immune system are discussed. PMID- 8219651 TI - Clinical significance of anaerobic bacteremias in a general hospital. A prospective study from 1988 to 1992. AB - A prospective study was designed to investigate anaerobic bacteremias and evaluate their incidence and significance in a general hospital. One or more blood cultures positive for anaerobic microorganisms were analyzed from each of a total of 61 patients hospitalized between January 1988 and April 1992, in accordance with an established protocol. The clinical repercussions of bacteremia were also analyzed. Two percent of blood cultures were positive for anaerobes, with an incidence of 0.6 cases per 1000 hospitalized patients. The most frequently isolated anaerobes were Bacteroides fragilis and Clostridium perfringens. Intraabdominal disease was the route of entry in 50% of the patients. A death rate of 37.3% was mostly attributed to B. fragilis. Hospitalization in the surgical department, nosocomial acquisition, previous surgery, critical initial clinical status and the presence of complications were significantly associated with increased death rates. No significant differences were found in the clinical course between patients whose antibiotic treatment was judged adequate and those for whom it was considered inadequate. The frequency and incidence of anaerobic bacteremia was low in our hospital. The well-known clinical and epidemiological characteristics of these infections facilitates their prompt diagnosis and empirical treatment with antibiotics of proven effectiveness against anaerobes. PMID- 8219652 TI - Overestimation of osteopenia using standard analysis software for peripheral quantitative computed tomography. AB - It is well established that measurement of bone mineral density (BMD) can estimate the risk of future fractures. To assess individual fracture risk BMD measurements are compared with a reference range provided by the manufacturer of the respective BMD technology. However, the power of trabecular bone measured by peripheral quantitative computed tomography (pQCT) to predict future fractures has not been shown up to now. We conducted measurements of trabecular bone density (TBD) at the distal radius (pQCT XCT 900, Stratec, Germany) in a sample of 506 healthy white women aged 40-60 years (mean 48) and compared the results with the manufacturer's normal range. We found a remarkable difference in TBD values between our healthy study population and the manufacturer's reference data in all age groups (e.g., age 50-54 years, 143.1 +/- 43.2 mg/cm3 versus 181.1 +/- 39.0 mg/cm3). Compared to the +/- 2 SD limits of the manufacturer's reference range our study population showed mean TBD values that were about 1 SD below the mean of the reference range. About 50% of our healthy cohort were below the -1 SD limit of the reference range. Almost ten times as many normal subjects as expected (22.1%) were found below the -2 SD limit and therefore classified as individuals with increased fracture risk. This overestimation of fracture risk leads to discomfort of the patient, unnecessary therapeutic intervention, and significant costs to the public.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219654 TI - No effect of insulin treatment or glycemic improvement on plasma carnitine levels in type 2 diabetic patients. AB - Carnitine is an essential factor for the transport of long-chain fatty acids and is important for the heart muscle. A longitudinal study in type 2 diabetic patients was carried out. Carnitine levels were observed before and during metabolic intervention with dietary measures and either sulfonylurea or insulin treatment. In both treatment groups a significant glycemic improvement was observed after 3 months (insulin treatment group: hemoglobin A1c 11.3 +/- 2.8 versus 7.0 +/- 1.0; sulfonylurea treatment group; hemoglobin A1c 11.3 +/- 1.4 versus 7.3 +/- 0.9). Carnitine levels did not differ from a control group and did not change significantly during the observed period. PMID- 8219655 TI - Systemic vasculitis positive for circulating anti-neutrophil cytoplasmic antibodies and with predominantly neurological presentation. AB - A 57-year-old male patient suffering from dramatically deteriorating diffuse and focal central nervous system symptoms was admitted to hospital after a short prodromal period in a somnolent state. He was diagnosed as having systemic vasculitis positive for circulating anti-neutrophil cytoplasmic antibodies, primarily involving the brain, but also most other organ systems. Circulating anti-neutrophil cytoplasmic antibodies are highly specific for Wegener granulomatosis, though they have been detected in rare cases of other vasculitic syndromes. Central nervous system lesions as presenting signs in Wegener granulomatosis have to be regarded as rare. This case nonetheless suggests that Wegener granulomatosis has to be considered in patients with a predominantly cerebral manifestation of a vasculitic syndrome. PMID- 8219653 TI - Human atrial natriuretic peptide in patients with type 1 diabetes mellitus: is it related to the development of diabetic nephropathy? AB - There is controversy as to whether increased plasma levels of human atrial natriuretic peptide (hANP) in patients with type 1 diabetes mellitus may contribute to the development of diabetic nephropathy. Therefore, we decided to conduct two studies to examine the relationship of hANP levels to urinary albumin excretion and blood pressure. In a cross-sectional study, 83 randomly selected type 1 diabetic patients were investigated. 19 of the patients had increased urinary albumin excretion. 45 healthy volunteers served as controls. In a longitudinal study, 19 type 1 diabetic patients were examined for one year at monthly intervals. An increased risk of eventually developing diabetic nephropathy was identified in 7 out of these patients by repeatedly revealing increased urinary albumin excretion. On the average, hANP levels were increased in type 1 diabetic patients in comparison to controls (P < 0.001). In both studies, hANP levels were positively related (P < 0.05) to mean arterial blood pressure. There was no correlation between hANP levels and metabolic control. hANP levels lay within normal range irrespective of normal or elevated urinary albumin excretion provided that mean arterial blood pressure was normal. In the longitudinal study, increased urinary albumin and alpha-1-microglobulin excretion preceded the increase in both hANP levels and mean arterial blood pressure. Although hANP levels were evidently not related to the disease mechanisms of early diabetic nephropathy, it is tempting to speculate that hANP may contribute to the vicious circle connecting diabetic kidney disease to hypertension once that its levels are increased by elevated blood pressure. PMID- 8219656 TI - Visceral leishmaniasis (kala-azar) after a visit to the Mediterranean region. AB - The case of a 17-year-old patient is presented who became ill 10 months after a holiday visit to Malta. Symptoms included fever peaking daily at 40 degrees C, pancytopenia, and splenomegaly. There was no evidence of bacterial or virological involvement, and probatory treatment with antibiotics followed by corticosteroids was without success. Examination of bone marrow led to the diagnosis of visceral leishmaniasis (kala-azar). A therapy with pentavalent antimony brought rapid improvement in clinical symptoms and led to complete recovery. A short review is presented of the epidemiology, diagnosis, and therapy of visceral leishmaniasis. The aim of this presentation is to remind the attendant physician of the clinical symptoms involved with the possible case of visceral leishmaniasis. PMID- 8219657 TI - Lyme disease associated with hemophagocytic syndrome. PMID- 8219658 TI - Kidney transplantation from cadaveric donors versus living related donors: improved results in the cyclosporine era. PMID- 8219659 TI - Effects of angiotensin-converting enzyme inhibition on renal sodium handling after furosemide injection. AB - The goal of this study was to quantitate the effect of angiotensin-converting enzyme inhibition on renal sodium handling after furosemide injection. The study was carried out on low and normal salt intake to assess potential interaction with salt balance. Eighteen healthy normotensive volunteers were examined in a double placebo-controlled parallel group design. Subjects were randomly put on either low-salt (20 mmol/day) or normal-salt (110 mmol/day) diet. In either arm of the diet volunteers were first treated orally with placebo for 1 week and subsequently with 2.5 mg/day of the angiotensin-converting enzyme inhibitor cilazapril for another 1 week. Cumulative 24-h urinary sodium excretion was measured on the 6th day of the respective week after sham injection and on the 7th day after injection of 40 mg furosemide. Compared to pretreatment with placebo, pretreatment with cilazapril resulted in a higher cumulative sodium excretion after furosemide injection (day 7) than after the sham injection (day 6) on both salt intakes. The difference in natriuresis (cilazapril versus placebo) was evident 2 and 3 h after injection of furosemide. Neither the time of onset nor the magnitude of antinatriuresis were affected by cilazapril. Following furosemide angiotensin II increased significantly even after cilazapril pretreatment. Cilazapril tended to reduce urinary furosemide excretion. At any given urinary furosemide concentration, the increment in urinary sodium excretion was significantly greater with cilazapril irrespective of salt intake. The study shows that (a) cilazapril increases furosemide-induced natriuresis irrespective of salt intake, (b) antinatriuresis is not affected by cilazapril, and (c) angiotensin II levels rise after furosemide on cilazapril in therapeutic doses. PMID- 8219660 TI - Different effects of eicosapentaenoic acid and olive oil on blood pressure, intracellular free platelet calcium, and plasma lipids in patients with essential hypertension. AB - In a randomized, double-blind, crossover study our specific aim was to examine the effects of a dietary fish oil or olive oil supplementation on blood pressure, intracellular free platelet calcium, plasma lipoproteins, and circulating vasoactive substances such as norepinephrine, epinephrine, and renin in patients with essential hypertension. Ten hypertensive patients (WHO classes I, II) were randomly assigned to receive 9 g fish oil or 9 g olive oil daily for 6 weeks after a 4-week baseline period. The 6-week treatment periods were separated by a 4-week wash-out. During treatment with fish oil diastolic blood pressure decreased from 103 +/- 1 to 98 +/- 2 mmHg (P < 0.05) but did not change significantly during olive oil intake. Systolic blood pressure was not affected by either treatment. Intracellular free platelet calcium decreased in patients receiving fish oil (from 102 +/- 8 nM to 86 +/- 6 nM, P < 0.05) but was not significantly altered by olive oil treatment. In contrast, the dose-response curve for thrombin-induced intracellular free platelet calcium was not altered by the fish oil enriched diet. Plasma triglycerides decreased by approximately 40% in the fish oil group while low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and total cholesterol were not altered. Renin activity, norepinephrine, and epinephrine in plasma were not influenced by fish oil supplementation. We conclude that a moderate increase in dietary fish oil reduces diastolic blood pressure, intracellular free platelet calcium, and plasma triglycerides in patients with essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219661 TI - A double-blind, randomized, placebo-controlled trial of n-3 fatty acid based lipid infusion in acute, extended guttate psoriasis. Rapid improvement of clinical manifestations and changes in neutrophil leukotriene profile. AB - Twenty patients hospitalized for acute psoriasis guttata with a minimum 10% of body surface area involvement (range 10-90%) completed a 10-day trial in which they were randomly allocated to receive daily infusions with either an n-3 fatty acid based lipid emulsion [100 ml/day with 2.1 g eicosapentaenoic (EPA) and 21 g docosahexaenoic acid (DHA)] or a conventional n-6 lipid emulsion (EPA + DHA < 0.1 g/100 ml). The severity of disease was evaluated by scoring daily erythema, infiltration, and desquamation and by a subjective scoring of clinical manifestations offered by the patients. Leukotriene (LT) and platelet-activating factor (PAF) generation were investigated in ionophore-stimulated neutrophils obtained on days 0, 1, 3, 5, 10, and 40. Moderate improvement in clinical manifestations was noted in the n-6 group (changes in score systems between 16 25% from baseline within 10 days). In contrast, the severity of disease markedly decreased in all patients of the n-3 group, with improvements in all score systems ranging between 45% and 76% within 10 days (P < 0.05 for each variable). The difference in response to the two regimens was evident within 4-7 days after onset of lipid infusion. A more than ten fold increase in neutrophil EPA-derived 5-lipoxygenase product formation (LTB5, its omega-oxidation products, non enzymatic degradation products of LTA5 and 5-hydroxyeicosapentaenoic acid) was noted in the n-3 group but not in the n-6 group. Neutrophil PAF generation increased in the n-6 group but decreased in the n-3 group. In conclusion, modulation of eicosanoid metabolism by intravenous n-3 fatty acid supplementation appears to exert a rapid beneficial effect on inflammatory skin lesions in acute guttate psoriasis. PMID- 8219662 TI - Influence of topical erythromycin preparations for acne vulgaris on skin surface pH. AB - Topical erythromycin is a standard regimen for inflammatory acne vulgaris because of its action against Propionibacterium acnes. Changes in P. acnes colonization are inducible by long-lasting changes of skin surface pH. Therefore, the influence of six erythromycin preparations with approximative pH values of 7.5 (preparation A) to 10.2 (C) on the skin surface pH was evaluated in healthy volunteers using a cross-over design. Following a 14-day run-in period, a constant skin surface pH (5.0) was found. Ten subjects received single doses 2-3 days apart; 20 volunteers applied preparations A and C for 28 days. Single doses of preparations A and E (pH 8.0) increased skin pH to 6.99 and 8.61, respectively, at 15 min; it then gradually declined. The other preparations induced only a minor rise of short duration. At the end of the long-term application, the skin surface pH amounted to 5.73 (A) and 5.39 (C). There was no correlation between the effect on skin surface pH and the approximative pH of the preparations. A close relation of single-dose and long term-effects was observed, however. The skin surface pH during the application of preparation A is high enough to increase P. acnes growth about fourfold as compared with normal skin and thus may counteract the antibacterial effect. Clinical relevance should be evaluated in a controlled clinical trial comparing the efficacy of preparation A with that of preparation C. PMID- 8219663 TI - Liposomes for atopic dry skin: the rationale for a promising approach. AB - Atopic dry skin characterized by a defect of the barrier function as determined by transepidermal water-loss measurements at the ultrastructural level shows an increase in membrane-coating granules (MCGs). MCGs are lamellar, ovoid organelles appearing in the stratum spinosum and stratum granulosum. MCGs consist of stacks of small parallel disks that are extruded and fuse to continuous lamellae. Liposomes, i.e., unior multilamellar vesicles composed of alternating lipid and water phases are structurally similar. Moreover, they also can form continuous lamellae. While phospholipids are generally used for liposome production, skin lipids and in particular ceramides can also be used. These lipids also seem to be the major components of MCGs. Hence, it seems advisable to use liposomes made of such lipids in the treatment of atopic dry skin. Apart from the probable inherent effect liposomes of this type may also apply particularly well for the delivery of active components. PMID- 8219664 TI - Effect of propranolol on portal vein hemodynamics: assessment by duplex sonography and indocyanine green clearance in healthy volunteers. AB - In the past decade several randomized trials have shown a beneficial effect of propranolol in cirrhotic patients. The effect of propranolol has been attributed to a reduction in portal vein pressure. So far the monitoring of portal vein hemodynamics following propranolol administration has been achieved mainly by hepatic vein catheterization. We studied the effect of propranolol on portal vein hemodynamics noninvasively in five healthy volunteers using duplex sonography and indocyanine green clearance. Measured by duplex sonography, blood flow was reduced by 28.6% in the portal vein (P < 0.05) and by 8.7% in the hepatic artery (NS) 60 min after oral administration of 80 mg propranolol. During this time total hepatic blood flow, measured by indocyanine green clearance, was reduced by 19.5% (P < 0.05). We conclude that both methods are useful for the study of portal vein hemodynamics during propranolol therapy, duplex sonography being more easily practicable. PMID- 8219665 TI - Treatment of pruritus: a new indication for serotonin type 3 receptor antagonists. AB - Generalized pruritus is a well-known, distressing symptom of various diseases, especially in hepatic cholestasis and chronic renal insufficiency. Its treatment is often unsatisfactory. In three patients with generalized pruritus, intravenous administration of the serotonin type 3 (5-HT3) receptor antagonist ondansetron induced a marked relief of itching. The effect was most pronounced in a patient with cholestasis-associated pruritus. It is suggested that serotonin, acting via 5-HT3 receptors, is involved in the generation and/or sensation of pruritus. Furthermore, 5-HT3 receptor antagonists may be a novel therapeutic principle for the treatment of pruritus. PMID- 8219667 TI - Detection of C-type natriuretic peptide compared with brain and atrial natriuretic peptide transcripts in human heart by the polymerase chain reaction. PMID- 8219668 TI - The role of the intensive care nurse--their choice. AB - An inability to attract and retain sufficient numbers of Registered Nurses (RN's), and Resident Medical Officer shortages in 1990 lead to a concern about who would provide services and whether RN's should "extend" their roles. This survey was developed to allow clinical nurses to identify what their role should be and to quantify the degree of role extension already occurring in the Intensive Care Units (ICU's) of New South Wales' hospitals. Surveys (823) were sent to 33 ICU's across New South Wales. Major Teaching (MTH), Suburban (SH) and Country (CH) hospitals were included in equal numbers. Nurse Unit Managers were contacted and agreed to the distribution of the questionnaire to all RN's working in these units. General demographic information was sought regarding experience in ICU, with the remainder of the questions related to whether nurses should take on extra tasks and what nursing duties could be relinquished. Overall return rate was 51.8% with variations in the type of hospital, MTH (35%), SH (57%), CH (68%). Nurses (72%) want to extend or already do have an extended role. However, they are very definite about what tasks they wish to perform and consistently throughout New South Wales do not wish to perform clerical tasks, some invasive procedures such as endotracheal intubation or arterial cannulation or prescribe medications. The majority of RN's want to relinquish non nursing duties such as cleaning, ordering supplies and clerical tasks. The study demonstrated that, a great many nurses working in ICU would like to and/or perceive the need for some role extension. Clearly nurses must be included in all discussions and decisions affecting their future. PMID- 8219669 TI - The use of casemix information in costing episodes of patient care for the acute hospital stay. PMID- 8219666 TI - Interleukin-6 in autoimmune disease. Role of IL-6 in physiology and pathology of the immune defense. PMID- 8219670 TI - Clinical decision making: a primer for preceptors. AB - The ability to apply the critical care nurses' knowledge, skills and attitudes to patient care requires clinical decision making at all phases of the patient-nurse interaction. As a novice critical care nurse, the patient care environment is often so complex as to overwhelm the orientee and prevent effective clinical decision making. This article includes a review of current strategies for teaching clinical decision making with special reference to critical care nursing. Relevant theoretical concepts in clinical decision making are applied to the clinical setting, particularly the orientation of novice critical care nurses. The approach is practical, with suggestions for the preceptor involved in the orientation process. As critical care nurses, we spend a major portion of our professional lives making decisions which will, to a greater or lesser extent, influence the hearts, the minds, and often the very survival of others. The process by which we make these decisions is sometimes mysterious even to the person making them. In order to improve our own decision making ability, and to enable us to teach new critical care nurses the skills needed in the critical care setting, we must explore and "demystify" this process. PMID- 8219671 TI - Declaration of Madrid on the preparation of critical care nurses. PMID- 8219672 TI - Should enrolled nurses work in the critical care area? PMID- 8219673 TI - [Effect of Astragalan on secretion of tumor necrosis factors in human peripheral blood mononuclear cells]. AB - The extracts of Astragalus membranaceus have been further isolated by liquid chromatography. One of the fractions (Astragalan, M.W. 20,000-25,000) could enhance the secretion of tumor necrosis factor (TNF) from human peripheral blood mononuclear cells (PBMC) in vitro. After isolation of adherent and nonadherent mononuclear cells from PBMC, Astragalan increased the secretion of TNF-alpha and TNF-beta respectively. These results suggest further study of Astragalan would promote the application of Astragalan in cancer immunotherapy. PMID- 8219674 TI - [Lipopolysaccharide-induced cellular immunity response and effect of herbal purgation method in intra-abdominal infection]. AB - The alterations of cytokines (TNF,PGE2), plasma lipopolysaccharide and their prognostic influences in 58 patients with intra-abdominal infection were observed with ELISA and RIA. The effect on physiopathologic process with herbal purgation method was explored. The results showed that as the level of plasma LPS raised the serum TNF, plasma PGE2 elevated obviously and the cellular immunity inhibited elevated in treatment and control groups. There was a linear positive correlation between the plasma LPS and the serum TNF in control group. Between the plasma PGE2 and CD4 lymphocytes of peripheral blood, it existed a linear negative correlation in treatment group. After two treatment courses, the recovery of abnormal indexes in treatment group was earlier than that in control group accompanied by escalation of lessened toxicity rate of LPS, more rapid in reducing the level and detectable rate of serum TNF, and the lowering of complication rate successively and the inhibition of cellular immunity tended to be relieved in treatment group. PMID- 8219675 TI - [Clinical and experimental study on effects of man-shen-ling oral liquid in the treatment of 100 cases of chronic nephritis]. AB - A new Chinese herbal preparation, Man-Shen-Ling (MSL, consisted of medicinal herbs such as Astragalus and Rehmannia) in treating 100 cases of chronic nephritis. The effective rate was 91% in comparing to 66.7% in the control group, P < 0.001. It was markedly effective for proteinuria, hematuria, improvement and recovery of renal functions, edema, anemia, anorexia etc in comparing with the control group. It showed no adverse effects on functions of liver, kidney, heart and GI tract. Animal model of chronic nephritis was established and the effects of MSL were observed. The laboratory findings and histopathological investigation on kidney revealed and confirmed that MSL has therapeutic effects on chronic nephritis. Pharmacodynamically, MSL exhibited effects of anti-allergy, its immuno suppressive effect corresponded to that of cyclophosphamide, with diuretic, hypotensive, proteinuria eliminating, anti-inflammatory, anti-coagulatory, renal blood flow and glomerular filtration enhancing, the excretion of urea-nitrogen, potassium and sodium promoting function; in addition, it also could promote and modulate the immunity. Acute and chronic toxicity tests on animal models neither showed toxic, mutagenic, teratogenic nor carcinogenic effects. It is a new preparation of Chinese medicinal herbs in treating chronic nephritis, it is safe and effective. PMID- 8219676 TI - [Clinical study of traditional Chinese medicine susceptible factors for senile lipid metabolic disturbance]. AB - The syndromes among 674 cadres over 45 years in age with case-control study were investigated, and the TCM susceptible factors (TCM-SF) of senile lipid metabolic disturbance (SLMD) were analysed statistically, which indicated that Kidney Deficiency, Phlegm-Turbid and Blood-Stasis were the main TCM-SF for SLMD. Compared with the results of presenility, it indicated that the Deficiency in origin was the intrinsic factors in development of LMD in presenile and senile period. Among which, Kidney-Deficiency possibly was the main factor. It is inferred the Deficiency in origin might cause the LMD in presenile and senile stage, and develop gradually as Syndrome of Deficiency in origin and Excess in superficiality, the latter aggravate the former as well. Both of these two Syndromes in origin affected the process of lipid metabolism. The results provided the prevention and treatment of SLMD, for further exploring the pathogenic factor and pathogenesis of the disease. PMID- 8219677 TI - [Assessment of early pregnancy detection with sphygmogram of smooth pulse]. AB - In order to assess the clinical availability of early pregnancy detection with Sphygmogram of smooth pulse, pulse pictures and endometrial tissues were simultaneously examined respectively with sphygmograph and pathological method in 205 cases of clinically diagnosed early pregnancy. Among them, 196 cases were pathologically confirmed as early pregnancy, 192 displayed smooth pulse on the Shygmogram. This shows the precision of sphygmogram of smooth pulse in detecting early pregnancy was 97.6%, its sensitivity 97.9%, Jordan index 0.868, specificity 88.9%, and misdiagnosis 11.1%. Though its specificity was not quite satisfactory, sphygmogram of smooth pulse has proved to be a sensitive index with high precision and easy management. Therefore, it is well worth to be popularized in China. PMID- 8219678 TI - [Antithrombotic effect of Gynostemma pentaphyllum]. AB - Human blood samples were investigated in vitro to observe the antithrombotic effect of water extract of Gynostemma pentaphyllum (GP). The results showed that GP could inhibit significantly the platelet aggregation induced by ADP and compound agonists (P < 0.05), accelerate obviously the disaggregation (P < 0.05) and inhibit effectively the experimental thrombosis (P < 0.05). The delayed effects of GP on KPTT, PT, TT, AT, RVV-RT, RVV-CT suggested that this drug could decrease the activity of multiple coagulation factors. And it showed that GP could accelerate the erythrocyte electrophoresis rate. This study revealed that GP is an antithrombotic agent affecting the links of thrombotic chain which is worthwhile to be studied further. PMID- 8219679 TI - [Anti-hyperlipemia and anti-oxidation effects of xue zhi ling]. AB - 92 cases with complete clinical data among 125 hyperlipemia patients were randomly divided into two groups: 51 cases in the Xue Zhi Ling treatment group and 41 cases in the control group with medication of panagin. The drugs were administered to all patients for 12 weeks and the blood lipid was then examined at the 4th, 8th, 12th week after medication respectively. In treatment group, there was the effect of lowering TC, TC-HDL/HDL and raising HDL at the 4th week (P < 0.05). However, there were no significant difference in above-mentioned parameters at the 4th, 8th and 12th week respectively. The experiment also showed that Xue Zhi Ling could reduce TG at the 8th and 12th week (P < 0.05). While there was no significant difference between that of the 8th and 12th weeks. The mean reduction of TC, TG and TC-HLD/HDL were 18.7%, 19.5% and 27.6% respectively, while the elevation of HDL in average was 17.4%. All of the lipid indexes in control group had no significant changes at any stage. In addition, it was shown that Xue Zhi Ling could decrease serum LPO at 12th week (P < 0.05). The results indicated that the Xue Zhi Ling has the effect of regulating the hyperlipemia and anti-oxidation. PMID- 8219680 TI - [Relation between urinary catecholamine content and hyperactivity due to yin deficiency in patients with hyperthyroidism]. PMID- 8219681 TI - [Effects of Rheum on renal hypertrophy and hyperfiltration of experimental diabetes in rat]. AB - Renal hypertrophy and elevated glomerular filtration rate (GFR) appeared in early stage of diabetic nephropathy (DN). In order to investigate the effect of Rheum officinale (RO) on the renal hypertrophy, streptozotocin induced diabetic rats with moderate hyperglycemia were divided into two groups, receiving RO (RO-DN) or not (DN), and one group of non-diabetic control (C) was set up. At the 28th day, DN group exhibited heavier kidney weight (+61%), more protein (+133%) and DNA (+94%) contents in the kidney and higher GFR (+94%) than the control. RO-DN rats showed much less above mentioned changes. In addition, lipid abnormalities were ameliorated in RO-DN group. This result suggest that RO is beneficial to the diabetes in terms of renal hypertrophy and GFR changes at early stage and is recommended in the treatment of diabetic nephropathy. PMID- 8219682 TI - [Effect of ginseng on antiperoxidate injury in myocardium and erythrocytes in streptozocin-induced diabetic rats]. AB - We have investigated the effect of ginseng on antiperoxidation in myocardium and erythrocytes of streptozocin-induced diabetic rats. In the group of ginseng administration (ginseng solution 0.2g/200g/day, lasting 15-16 days), there was a significant decrease in the level of fasting blood-glucose and lipid peroxide (LPO) in myocardium and erythrocytes, in comparing with that of model group, P < 0.05. The activity of superoxide dismutase (SOD) in myocardium and erythrocytes in group of ginseng administration was increased, P < 0.05, compared with that of model group and vitamin E treatment group. The mechanisms of antiperoxidation effect of ginseng might include the following: 1) By lowering the level of fasting blood-glucose, decreasing the rate of monosaccharide auto-oxidation and partially protecting the production of free radicals; 2) Elevating the activity of enzymatic free radicals scavenger in cells, such as SOD; 3) directly eliminating the superfluous free radicals. PMID- 8219683 TI - [Effects of jiang tang tong mai ning on serum ascorbyl radical, superoxide dismutase activity, lipid peroxide level and tissue free oxygen radical in diabetic rats]. AB - The effect of Jiang Tang Tong Mai Ning treatment on body weight, the level of blood sugar, the serum ascorbyl radical, SOD activity, LPO level and peroxidic radial (O2.-) of heart and kidney tissue in alloxan induced diabetic rats were observed. The results were also compared with that of Jiang Tang Jia Pian and vitamin E treated groups, which showed that the level of blood sugar, the level of serum ascorbyl radical, the concentration of LPO and peroxidic radical (O2.-) of myocardium and kidney tissue decreased significantly respectively (P < 0.01, 0.01, 0.01, 0.05), and the body weight, SOD activity increased obviously after the treatment (P < 0.05). For the first time, a W-wave between S-peak and T-peak of ESR spectrum in the tissue of rat, which is similar to the form of Fe-Mo flavoprotein has been observed in this investigation, a positive correlation appears to exist between A value and the corresponding G value of W-wave. PMID- 8219684 TI - [Diabetes mellitus of qi-yin deficiency type treated by hypoglycemic Chinese herbal tablets. Report of 60 cases]. PMID- 8219685 TI - [Recommendations on an excellent book entitled "The Progress of Chinese Medicinal Herbal Pharmacology and Clinical Study"]. PMID- 8219686 TI - [Radioimmunoassay analysis in traditional Chinese medical and pharmaceutical studies]. PMID- 8219687 TI - [Recent development of prevention on asthma with traditional Chinese medicine]. PMID- 8219688 TI - Histology of alveolar bone and primary tooth roots in a case of cleidocranial dysplasia. AB - Cleidocranial dysplasia is commonly reported as an autosomal dominant inherited condition with defective formation of clavicles, malformation of the craniofacial bones, very slow exfoliation of the primary teeth and failure of the eruption of the permanent dentition. Lack of clinical resorption of the roots of the deciduous teeth and/or surrounding bone, lead to eruption failure of permanent teeth. Histopathological study (light and scanning electron microscopy), in a case of cleidocranial dysplasia, gives prominence to the hypothesis of abnormal remodelling of bone and cementum. PMID- 8219689 TI - Morphometric analysis of mandibular canal: clinical aspects. AB - Results of morphometric analysis of the mandibular canal (MC), carried out on 105 conserved mandibles, 70 being dentate and 35 edentate, was performed. The analysis was carried out on consecutive sections, at mutual intervals of 0.5 cm. In the mandibular ramus sections were carried out obliquely, approximately in the frontal plane, and horizontally, from mandibular foramen to the lowest region of the vertical part of the MC (all together two sections). In the mandibular corpus, consecutive transversal sections were carried out between existing teeth, or at mutual intervals of 0.5 cm in edentate regions. The obtained results pointed out the very close relationship between the MC and lingual cortical plate of the mandibular ramus. In its horizontal part, the average diameter of the MC was 2.6 mm. It was situated more lingually in the molar region; towards the front, it approached the vestibular cortical plate, being closest to it in the region of the second premolar. Similar relationships of the MC and both cortical plates existed in edentate jaws. Relationships of the MC and tooth root apices varied; however, the MC was closest to the apices of the third molar. Mesially from the mental foramen, a clearly defined incisive canal was present in 92% of the dentale mandibles, but only in 31% of the edentate ones. The nearest to the incisive canal was the apex of the first premolar. The authors point out the importance of presented results in everyday practice, especially in oral and maxillofacial surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219690 TI - Light and laser scanning microscopy analysis of hydroxyapatite used in periodontal osseous defects in man: evidence of a different resorption pattern in bone and soft tissues. AB - Hydroxyapatite (HA) is a highly biocompatible material that recently has been shown to undergo biodegradation. The mechanisms of this phenomenon are unclear, and humoral and cellular events have been thought to be implicated. In the present study HA particles were put into infraosseous defects on teeth that were to be extracted for prosthetic reasons and then retrieved after a 1-year period. The specimens were processed with the cutting grinding system. Results show a very sharp difference of the biodegradation processes, related to the tissues that surround the HA particles. HA in tight contact with mineralized bone showed no evidence of degradation or resorption, while on the contrary, in the areas where bone loose connective tissue was present, it was possible to observe HA crystals detached and scattered in cells cytoplasm or extracellular fluids. This dissolution and resorption phenomenon were observed also by Laser Scanning Microscope (LSM) in fluorescent mode. These differences in degrees of degradation between bone and loose connective tissue could be due to the small amount of interstitial fluid present in mineralized bone and the greater flow of fluid through connective tissue. PMID- 8219691 TI - [The demonstration of a methodology for identifying and analysing oxygenated sterols present in radicular cysts]. AB - Our work has two main aims: to identify oxygenated sterols that accompany cholesterol in dental cyst and to develop effective methods for "profile" analyses of these sterols. Attention as focused on a family of products derived from cholesterol, characterized by the presence of one or more oxygenated functions. More than fifty of these oxysterols are known and find most of time in different parts of the body. In the procedure, lipids are isolated from dental cyst, the fraction is trimethylsilylated and analysed by capillary gas chromatography. Sterols are identified by comparison with reference compounds. However, two sterols of particular interest, viz cholesterol alpha and beta epoxides, are so easily produced from cholesterol (even when rigorous precautions are taken) that indirect methods of analysis are strongly advisable. An adequate degree of quantification is possible for sterols such as 26-hydroxycholesterol (26OHCL), which do not arise significantly as artefacts. Even to verify the fraction which seems to be 26OHCL we used thin layer chromatography coupled with mass spectrometer. PMID- 8219692 TI - [Postorthodontic retention with a rigid resin splint]. AB - We have done a clinical review of 30 cases of post-orthodontic retention with resin splint, from canine to canine in both maxillary. We describe the procedure of making the splint, its placement, their incidence or clinical problems (inadequate adhesion, gingivitis...) and the psychologic or subjective patient aspects. PMID- 8219693 TI - [The clinical value of the surface EMG in dentistry]. PMID- 8219694 TI - Determination of rafoxanide and closantel in ovine plasma by high performance liquid chromatography. AB - A high performance liquid chromatographic method has been developed for the determination of rafoxanide and closantel in ovine plasma. Acetonitrile and chloroform were used for the extraction. The mean recoveries were 78.69% and 80.59% for rafoxanide and closantel, respectively. This method was applied to the characterization of rafoxanide plasma kinetics following oral administration of therapeutic doses to sheep. PMID- 8219695 TI - Liquid chromatographic evaluation of purine production in the donor human heart during transplantation. AB - A reversed phase high performance liquid chromatographic technique is presented allowing purine catabolite determination in a whole blood extract without a prior purification step. The method was applied to determine the timing and the profile of myocardial nucleotide catabolite release during reperfusion of the transplanted human heart. Samples of arterial and coronary sinus blood collected at various times within 1 h after aortic declamping during heart or heart-lung transplantations were used for nucleotide catabolite determination. Massive release of inosine and hypoxanthine from the heart was demonstrated. Production of adenosine was also shown but there was no liberation of xanthine or uric acid. Nucleotide catabolite release was greatest in the first 5 min (coronary sinus arterial difference = 15-20 microM), but was still significant after 30 min of reperfusion. The determination of inosine and hypoxanthine--major catabolites released--was found to be reproducible in coronary sinus blood (coefficient of variation < 10%). However, immediate protein precipitation afer blood sample collection was necessary, as rapid metabolism of both exogenous and endogenous adenosine and inosine was demonstrated. PMID- 8219696 TI - Gas chromatographic determination of mexiletine in human plasma with flame ionization detection after reaction with carbon disulphide. AB - A gas chromatographic method for the determination of mexiletine in human plasma is described. Mexiletine was simultaneously extracted and derivatized with carbon disulphide for separation and quantitation on a glass column (1.5 m x 3 mm i.d.) packed with 1.5% OV-1 coated on 80-100 mesh Shimalite W (201D). The method required only 0.5 mL of plasma and could detect as little as 10 ng of mexiletine. It has been applied to the study of the pharmacokinetics of mexiletine in healthy volunteers. PMID- 8219697 TI - Thermal desorption-gas chromatographic determination of ethane and pentane in breath as potential markers of lipid peroxidation. AB - Formation of free radicals and lipoperoxidation occur at the onset of cellular damage. These effects are produced during normal metabolism and in pathological states. The peroxidation of polyunsaturated fatty acids, i.e. linoleic acid and linolenic acid, which are both cellular membrane compounds, induces ethane and pentane formation in pulmonary air exhalation. These two volatile hydrocarbons can be considered as potential lipoperoxidation markers. Methodological difficulties limit the use of these gases for assessment of free oxygen radical activity but we have developed and validated a non-invasive technique. A study was performed with ten healthy volunteers. PMID- 8219698 TI - Simple analysis of amoxycillin in plasma by high performance liquid chromatography with internal standardization and ultraviolet detection. AB - A simple high performance liquid chromatographic method with ultraviolet detection at 229 nm is described for quantitation of amoxycillin in plasma. After deproteination of plasma samples with perchloric acid and adjustment of the pH to 4.9, the supernatant was injected onto a reversed phase C18 column, using acetonitrile:phosphate buffer (0.01 M, pH 7.4) (1:25 v/v) as the mobile phase. Amoxycillin and the internal standard, cefadroxil, were eluted at 23 min and 12 min, respectively, without interference from endogenous substances. Processed samples were stable for at least 24 h at room temperature which permitted automated batch processing overnight. Calibration plots of the amoxycillin to cefadroxil peak-height ratio vs. amoxycillin concentration were linear (P < 0.0001; r > or = 0.995) from 0.25 mg/L to at least 16.0 mg/L. Between-day and within-day imprecision (CV) ranged between 3.7% and 17.7%. Absolute recovery for amoxycillin and cefadroxil exceeded 82%. The application was demonstrated by the analysis of amoxycillin in human plasma after a single oral dose of amoxycillin (250 mg) suspension. PMID- 8219699 TI - Fluorescence and chemiluminescence detection of oxazole-labelled amines and thiols. AB - Fluorescence and chemiluminescence analyses of amino acids and thiols derivatized with 2-fluoro-4,5-diphenyloxazole (DIFOX) and 2-chloro-4,5-bis(p-N,N dimethylaminosulphonylphenyl)oxazole (SAOX-Cl) were investigated. Thirteen diphenyloxazole (DIOX)-derivatized amino acids were separated within 38 min by a linear gradient elution from 100% A [0.05 M phosphate (pH 7.0): CH3CN (75:25)] to 100% B [0.05 M phosphate (pH 7.0):CH3CN (1:1)] over 30 min and an isocratic elution of 100% B for 30 min. The detection limits (S/N = 2) with fluorescence detection were in the range of 19-64 fmol. Thiols derivatized with SAOX-Cl were separated by an isocratic elution using 0.1 M H3PO4:CH3CN (65:35) and detected fluorimetrically. The detection limits (S/N = 2) of reduced glutathione, N acetylcysteine, 2-mercaptopropionylglycine, cysteine, homocysteine and captopril were 1.2, 1.5, 1.9, 5.7, 6.4 and 7.9 fmol, respectively. Peroxyoxalate chemiluminescence (CL) intensities of sulphonyl-5-N,N-dimethylaminonaphthalene (DNS), SAOX and DIOX derivatives were compared using three different oxalate esters (DFPO, TCPO and TDPO) by flow injection analysis. The relative chemiluminescence intensity (RCL) of SAOX-proline and DIOX-proline were 76-80% and 19-25% of DNS-proline (100%), respectively. Other SAOX and DIOX derivatives showed lower CL intensities (< 12%). Extremely low CL intensities were obtained for the fluorescent tagging reagents (< 0.11%) and their hydrolysis products (< 0.80%). Secondary amino acids and peptides, derivatized with DIFOX in aqueous media at room temperature for 1 h, were detected using DFPO/H2O2. TCPO/H2O2 and TDPO/H2O2 after separation by high performance liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219700 TI - High performance liquid chromatography of penicillins with penicillin-enhanced luminol chemiluminescence detection. AB - A high performance liquid chromatographic method with chemiluminescence detection for the determination of penicillin G and ampicillin is reported. The method is based on the enhancement of the luminol chemiluminescence with beta-lactam antibiotics. The linear relationship was obtained between the peak height and the concentration of penicillin G or ampicillin up to 15 nmol per 20 microL injection. Detection limits were 1 nmol for penicillin G and 0.5 nmol for ampicillin with a signal-to-noise ratio of 2. Relative standard deviations for five replicate measurements of 4 nmol/injection each of penicillin G and ampicillin were 2.1 and 2.3%, respectively. PMID- 8219701 TI - Separation of reduced and oxidized glutathione by micellar electrokinetic capillary chromatography. AB - The separation of reduced and oxidized glutathione at an absolute sensitivity of about 100 pg by micellar electrokinetic capillary chromatography without derivatization is described. The time required for the separation is less than 10 min (the time between two following injections is about 15 min). The separation is characterized by high efficiency and good reliability. A partition mechanism is responsible for the high resolution observed. The method was utilized for the analysis of commercial preparations of glutathione and a good agreement with the expected results was obtained; the oxidation of the commercial glutathione in solution was easily analysed. PMID- 8219702 TI - High performance liquid chromatographic determination of levomepromazine in human breast milk and serum using solid phase extraction. AB - A high performance liquid chromatographic (HPLC) method has been developed for the determination of levomepromazine in human breast milk and serum. The levomepromazine was extracted by a rapid and simple extraction method using a Sep Pak C18 cartridge. The extracts were separated by HPLC on a C8 bonded reversed phase column and detected by UV absorbance at 254 nm. There was no interference with endogenous substance in human breast milk and serum. A linear relationship was obtained for the levomepromazine over the concentration range of 10-300 ng/mL. The recoveries of levomepromazine added to human breast milk and serum were 92.5-99.1% and 86.9-103.9%, respectively. PMID- 8219703 TI - A rapid and sensitive determination of salmon calcitonin in solutions containing bovine serum albumin or gelatin. AB - A sensitive and selective reversed phase high performance liquid chromatographic method was introduced for the determination of salmon calcitonin (sCT) in solutions containing bovine serum albumin or gelatin. The method was based on the sensitive fluorescence detection of sCT by postcolumn derivatization with o phthal(di)aldehyde. The sample was loaded onto a reversed phase column, purified by column switching and separated with linear gradient elution using the ion pair technique. A linear relationship was obtained between the peak height and the amount injected in the concentration range 1-40 ng. The detection limit was 10 ng/mL (S/N = 3) at a sample injection volume of 100 microL. PMID- 8219704 TI - Determining the patient's temperament: an excursion into seventeenth-century medical semeiology. PMID- 8219705 TI - Abdominal paracentesis: a casualty of reductionist medical therapeutics. PMID- 8219706 TI - Cortisone and the politics of empire: imperialism and British medicine, 1918 1955. PMID- 8219707 TI - The obstetrical casebook of Walter Channing, 1811-1822. PMID- 8219708 TI - Quantitative analysis of smooth endoplasmic reticulum proliferation in periportal, midzonal and perivenular hepatocytes of mice after administration of phenobarbital. AB - Smooth endoplasmic reticulum (SER) proliferation after phenobarbital (PB) administration has been described to occur predominantly in perivenular hepatocytes. We analyzed by quantitative electron microscopy changes in ER amounts in periportal, midzonal and perivenular hepatocytes from mice injected with 35, 50, 100 or 150 mg/kg of PB once a day for 3 days. The SER proliferated in midzonal hepatocytes in addition to perivenular hepatocytes even when low doses (35 or 50 mg/kg) were administered, and in hepatocytes of all three zones in case of high doses (100 or 150 mg/kg). Moreover, net proliferation of SER after administration of an amount of PB was not different in hepatocytes of any zones where the proliferation occurred, except animals injected with 100 mg/kg. The results suggest that there is no difference in SER producing capacity in hepatocytes of three zones when the cells have recognized the stimulation of PB. PMID- 8219709 TI - Neuronal damage in the rat hippocampus induced by in vivo hypoxia. AB - Rats were subjected to hypoxia for 30 min in a chamber containing 5% O2 and 95% N2. The distribution of damaged neurons in the hippocampus was then examined at various predetermined times, ranging from 3 hours to 21 days after hypoxia. Hematoxylin-eosin stained sections showed shrunken and eosinophilic neurons in the CA3 and CA4 regions. Similar, but less severe, changes were also observed in the granule cell layer of the dentate gyrus. In contrast, neurons in the CA1 region were relatively resistant to hypoxia. These results showed the susceptibility of the hippocampus to hypoxia, although the affected neurons are not the same as those vulnerable to ischemia. PMID- 8219710 TI - Xenogeneic antibodies against hepatocyte plasma membranes suppress bile secretion in rats. AB - The action of xenogeneic antibodies against rat hepatocyte plasma membranes which were injected into the portal vein in the dose of 40 mg of protein per kg of body mass on the bile secretion and on the ultrastructure of the liver were studied. It was shown that these antibodies suppressed the bile flow, the secretion of bile acids and cholesterol and decreased the bile salt-independent bile flow. The action of antibodies was accompanied by ultrastructural damage of sinusoidal and lateral plasma membranes of some hepatocytes and by a decrease in the Na+, K(+) ATPase activity. It was concluded that the decrease of Na+, K(+)-ATPase activity in the plasma membranes was the most important mechanism responsible for a decrease in the bile flow. PMID- 8219711 TI - Ultrastructural morphometric investigation of the heart of rabbits after a single administration of reserpine. AB - The ultrastructure of myocardial cells of chinchilla rabbits was morphometrically examined after administration of one dose of reserpine. The results show that 24 hours after administration of reserpine, there is a decrease in the number and an increase in the size of the mitochondria, a relaxation or narrowing and ramification of myofibrils, an increase in intracellular lipid content compared with control animals. These changes are the result of functional and chemical desympathization and they represent an ultrastructural-morphometric characteristic of the action on cardiomyocytes. PMID- 8219712 TI - Postnatal development of the rat CNS following in utero exposure to a low dose of ionizing radiation. AB - In utero exposure to ionizing radiation is of importance because of its potential health risks. The developing nervous system is particularly vulnerable and the consequences of exposure to low levels of radiation (< or = 1 Gy) are not well established. The developmental effects of maternal exposure to 50 cGy gamma radiation on gestational days (GD) 9.5, 15, and 18 were investigated in Sprague Dawley rats. Rats exposed on GD-9.5 along with appropriate controls were killed at 4 h, 48 h, and 10 days post-irradiation while those irradiated on GD-15 and GD 18 were killed postnatally (PN) on days 7 and 26. All were examined for developmental anomalies and representative samples of brains were processed for microscopic study. No significant developmental differences were observed between irradiated and control embryos killed 48 h after irradiation on GD 9.5. However, in irradiated fetuses a larger number of developmental anomalies were observed at term. Defects of the eye and of spinal curvature were the most common malformations encountered. Mitoses were reduced within the neuroepithelium of embryos irradiated on GD-9.5 and evidence of pyknosis and necrosis was seen 4 h after irradiation. The capacity of surviving primitive neural cells for repair, however, was such that by 48 h after exposure the irradiated nervous system no longer differed from controls. Rats irradiated on GD-15 and GD-18 and examined on PN-26 exhibited clusters of small, dark, pyknotic neurons within the hippocampal and dentate gyri, often bilaterally.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219713 TI - Histopathological observation of joint lesions of extremities in mice transferred genome. AB - Pathological examination of arthritic lesions in transgenic mice produced by the pX region of the human T-cell leukemia virus type-1 (HTLV-1) was carried out. Clinically, erythema, swelling and/or ataxia of the limb joints were observed in many transgenic mice about 1 month-old. Histopathologically, proliferation of synovial lining cells, infiltration of inflammatory cells with lymphoid structures and formation of pannus with cartilage and/or subchondral bone destructions were observed in various joints of transgenic mice. The frequency of abnormalities in the joints was higher in females than in males. These histopathological findings were very similar to those of human rheumatoid arthritis (RA). Present results indicate that the pX genome of the HTLV-1 is an etiological agent for the incidence of arthritic lesions in the transgenic mice. PMID- 8219714 TI - Oval cells--hepatocytes relationships in Dipin-induced hepatocarcinogenesis in mice. AB - During Dipin-induced hepatocarcinogenesis in mice there is powerful and prolonged proliferation of oval cells which are arranged in duct-like structures. Ultrastructure and differentiation pathways of oval cells depend on their location in the liver lobule. The major part of oval cells is represented by duct lining cells morphologically similar to biliary epithelial cells. They form the system of branching anastomozing ducts and expand into the parenchyma from portal to central veins. Later these ducts disintegrate. In the periportal areas, three stages of oval cell differentiation can be distinguished: (1) low differentiated cell similar to cells of terminal biliary ductules in their size and ultrastructure, (2) transitional cells and (3) young hepatocytes. Cells with ultrastructural characteristics of sequential stages of hepatocyte differentiation are located within the ducts surrounded by the basal lamina. Our data suggest that oval cells are the committed cell precursors capable of differentiating into hepatocytes or biliary epithelial cells in the periportal microenvironment. PMID- 8219715 TI - Effect of nilvadipine on adrenocortical cell proliferation and steroidogenesis in early stage of adrenal regeneration. AB - The influence of nilvadipine, a novel calcium channel antagonist on adrenal regeneration was investigated in male Wistar rats. The estimation of the mitotic index after administration of colchicine was supplemented by an immunoperoxidase technique with monoclonal antibodies to bromodeoxyuridine. Plasma corticosterone was determined by a radioimmunological assay. Nilvadipine was given subcutaneously in two doses (0.2 and 1 mg/kg) to animals subjected to adrenal enucleation combined with contralateral adrenalectomy. It was found that nilvadipine inhibited the proliferation ratio of adrenocortical cells on the 4th day after surgery in a dose-dependent manner. The inhibitory effect of nilvadipine became less significant by 8 days after operation. However, no changes in corticosterone secretion were observed. PMID- 8219716 TI - Hepatic failure after partial hepatectomy due to synergism between endotoxaemia and congestion of the liver. AB - To determine whether hepatic failure after partial hepatectomy is due to synergism between endotoxaemia and congestion of the liver, we examined endotoxin hepatotoxicity in partially hepatectomized rats with and without congestion of the liver. In partially hepatectomized rats without congestion of the liver, endotoxin administration induced slight elevation of the serum transaminase activity and mild or moderate hepatocellular necrosis in a few rats: these findings were not significantly different from those in sham operated rats treated with endotoxin. On the other hand, in partially hepatectomized rats with congestion of the liver, endotoxin administration induced marked elevation of serum transaminase activity and moderate or severe hepatocellular necrosis in almost all rats: these findings were significantly different from those in endotoxin-treated partially hepatectomized rats without congestion of the liver. These experimental data suggest that synergism between endotoxaemia and congestion of the liver may be a cause of hepatic failure after partial hepatectomy. PMID- 8219717 TI - Genetic determinants of visual functions. AB - Recent studies on the molecular genetics and biochemistry of cone and rod photoreceptors have contributed significantly to our understanding of the basis for variation in normal and anomalous color vision in human populations, and for some of the hereditary eye diseases characterized by retinal degeneration. PMID- 8219718 TI - A rich complexity emerges in phototransduction. AB - Over the past two decades there has been an explosive growth in our understanding of phototransduction, leading to the development of a comprehensive scheme for the process. On the basis of this scheme the finer details of the process are being elucidated. Additional protein components and pathways have been identified, successful quantitative models of parts of the process have been developed, and a detailed understanding of the molecular basis of physiological function has begun to emerge. Here we summarize the most recent developments. PMID- 8219719 TI - Synaptic transmission and modulation in the olfactory bulb. AB - Recent work in molecular biology and synaptic physiology has significantly increased our understanding of inhibitory and excitatory mechanisms in the olfactory bulb. Multiple subtypes of amino acid receptors with different functional and neuromodulatory properties are likely to play key roles in processing odor information transduced and relayed to the olfactory bulb by the olfactory sensory neurons, and in modulating that information during olfactory learning. PMID- 8219720 TI - Olfactory imprinting. AB - The term imprinting is used to refer to biologically relevant learning during a sensitive period defined by a particular developmental stage or physiological state. Although olfactory imprinting may occur at any age, and some of the best studied paradigms involve adult animals, recent reports of long-term memory for odorants experienced during prenatal life present a particular challenge to our understanding of olfactory learning. Firstly, it is possible that these paradigms represent a form of exposure learning based on mechanisms different to the more familiar associative paradigms. Secondly, given the substantial addition of neural elements occurring during the perinatal period, these paradigms raise the question as to how the olfactory system, and eventually the brain, is able to acquire and retain information under conditions of major neural growth and change. PMID- 8219721 TI - Olfaction in invertebrates. AB - Olfactory transduction in invertebrates seems to be similar to that in vertebrates. Three signalling systems involving activation of adenylate cyclase, phospholipase C and guanylate cyclase are present. A variety of second messengers, including cAMP, inositol 1,4,5-trisphosphate, diacylglycerol, nitric oxide and Ca2+, have been identified but their target sites and mode of action are not yet fully understood. The central projections of olfactory signals in invertebrates are relatively simple and perhaps more hard-wired than in vertebrates. Information about circuitry and functional mapping in the olfactory pathway is lacking. This is essential for understanding the sensory code and higher olfactory functions. Neurogenetic analysis has provided useful insights into olfaction and olfactory learning. PMID- 8219722 TI - Early events in auditory processing. AB - During the last year, further evidence has appeared concerning the basis of frequency selectivity in the cochlea, which may ultimately depend on a motile mechanism residing within the walls of the outer hair cells. Evidence has also appeared on hair-cell mechanotransduction, and on the way that the stimulus is coupled to the mechanotransducer channels. PMID- 8219723 TI - Audition in echolocating bats. PMID- 8219724 TI - Learning-induced changes of auditory receptive fields. AB - Classical conditioning specifically modifies receptive fields in primary and secondary auditory cortical areas to favor the frequency of a tone signal over other frequencies, including tuning shifts toward, or to, this frequency. This plasticity of receptive fields is associative and highly specific, can develop very rapidly, can be expressed under anesthesia and can be maintained indefinitely. Muscarinic receptors in the cortex may be involved. Non-lemniscal thalamic nuclei also develop receptive field plasticity that may contribute to cortical plasticity. PMID- 8219725 TI - Visual pathways supporting perception and action in the primate cerebral cortex. AB - Behavioral and electrophysiological evidence suggests a new interpretation of the division of labor between the ventral and dorsal streams of visual processing in primate cerebral cortex. It is suggested that the ventral stream mediates the perception of objects while the dorsal stream mediates the on-line control of skilled actions directed at those objects. PMID- 8219726 TI - Response synchronization in the visual cortex. AB - Recently, the classic idea of a 'relational' code in the brain received new impetus from the observation of stimulus-dependent synchronizations in the visual cortex. Work over the past two years has focused on documenting the functional dependencies of such synchronizations. We review and classify the experimental findings with respect to separate spatial and temporal schemes. Thus, we distinguish between different signal classes (spikes, continuous signals), and different types of time-locking to the stimulus. These various classes of synchronization phenomena are discussed with regard to their properties, the underlying mechanisms and their possible relevance for visual processing. PMID- 8219727 TI - The role of spatio-temporal firing patterns in neuronal development of sensory systems. AB - The emergence of precise and orderly sets of neuronal connections often depends upon coordinated electrical activity during the early stages of development. In recent years, an increasing number of reports have shown that neurons of immature sensory systems can spontaneously generate electrical activity that occurs synchronously amongst adjacent cells. These patterns of correlated activity seem to be well suited to the role of providing the cues that are necessary for the activity-dependent refinement of the neural connections in the developing visual, auditory and somatosensory pathways. PMID- 8219728 TI - Central hyperexcitability triggered by noxious inputs. AB - Repetitive activity in unmyelinated sensory afferent neurones, arising from electrical stimuli, tissue injury or nerve damage, can induce long-lasting sensitization in dorsal horn neurones. This process can be blocked by antagonists of the NMDA receptor. In the past year it has emerged that sensory neuropeptides and nitric oxide are also essential mediators of this phenomenon. PMID- 8219729 TI - The pharmacology of pain signalling. AB - Recent advances in pain research illustrate the analytical power of modern neurosciences in a field previously accessible only to methods of systems biology. Novel molecular and cellular biological techniques have changed the face of pain research by detailing the multiplicity of pain transducing and pain suppressive systems which involve neuronal and hormonal systems acting in concert to help the individual to cope with pain. The introduction of concepts of neuronal plasticity in this field has led to important therapeutical consequences. Novel compounds and new regimens for drug treatment to prevent activity-dependent long-term changes or to facilitate extinction in pain-related systems are emerging. PMID- 8219731 TI - Sensory systems. PMID- 8219730 TI - Central core modulation of spontaneous oscillations and sensory transmission in thalamocortical systems. AB - Central core (brainstem, diencephalic and basal forebrain) systems influence the functional modes of thalamic and cortical neurons during behavioral states of vigilance. Recent studies in vivo and in vitro have focused on the cellular properties of central core systems and their modulation of slow sleep oscillations, fast rhythms during arousal and dreaming state, and the fine inhibitory sculpturing of afferent signals. PMID- 8219732 TI - Does type II diabetes predispose to retinal vein occlusion? AB - Retinal vein occlusion (RVO) not infrequently occurs in diabetic patients. Although the aetiology is unclear, it could relate to the other microvascular complications of diabetes. In the non-diabetic, both the central (CRVO) and branch (BRVO) forms are commonly associated with hypertension and hyperlipidaemia. We have therefore studied fifty type II diabetic patients with RVO compared to a carefully matched diabetic control group (n = 50) to elucidate underlying medical conditions and hence the aetiology of RVO in diabetic patients. The two groups were well matched. Diabetics with RVO showed a strikingly high prevalence of hypertension compared to the controls (72% versus 32%: p < 0.001) and a trend to increased hyperlipidaemia (54% versus 36%). Diabetic microvascular complications were more common in the control group (diabetic retinopathy and proteinuria). No significant differences were observed in mean HbA1 or weight, but current smoking habits and blood pressure levels were increased in the diabetics with RVO. 80% of diabetic patients with the BRVO form, were hypertensive. We conclude that the main underlying medical conditions for RVO in diabetics are hypertension and hyperlipidaemia, and these may be important in the aetiology as in the non-diabetic. RVO is more common in type II rather than type I diabetes, and does not associate with the presence of diabetic microvascular complications. Clinical assessment for hypertension and hyperlipidaemia is therefore important in diabetic patients with RVO, especially if recurrence of the condition and further visual loss is to be prevented. PMID- 8219733 TI - Prognostic value of visual evoked responses in childhood amblyopia. AB - We assessed the possible clinical utility of pattern reversal visual evoked potentials in predicting the success of pleoptic treatment. Thirty amblyopic children--16 strabismic, 11 anisometropic and three of refractive type (in all cases the amblyopia was monocular)--and ten children without amblyopia (control group) were examined by conventional psychometric methods. Visual evoked potentials (VEP) to pattern reversal stimulation were also recorded. The amblyopic group was treated with occlusion of the preferred eye for three to six months. Psychometric and VEP tests were repeated in 15 amblyopic children after the treatment. The pre-treatment VEP amplitude side-differences (between amblyopic and better fellow eye) were significant, with first positive wave, P1, being invariably lower on the amblyopic side. We correlated the side-differences in visual acuity with the corresponding side-differences in amplitude and latency of the P1 wave. In the former the correlation coefficient was r = 0.47 (p < 0.01), and in the latter r = 0.65 (p < 0.01). Latency was prolonged in the eyes with significantly reduced visual acuity in which the wave form was also typical for amblyopia. We then correlated the difference between pre- and post-treatment visual acuity of the amblyopic eye with the pre- and post-treatment difference in amplitude (correlation coeff. r-0.51 (p = 0.05)) and latency of the P1 wave (correlation coeff. r = 0.40 (p > 0.05)).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219734 TI - Long-term follow-up of iodine-125 brachytherapy for choroidal melanomas. Part I: Anatomical results and life expectancy. AB - We report a prospective study of 19 choroidal melanomas treated with iodine-125 plaque from 1984 to 1989. The mean tumor height was 5.8 mm, base diameter 11.6 mm, and tumor volume 80 to 510 mm3. The mean radiation dose to tumor apex was 70 Gy and scleral contact dose 355 Gy; tumor base was surrounded by contiguous laser or cryopexy lesions. Follow-up was 27 to 84 months (mean 60 months). All tumors regressed at least 50% in volume with no tumor regrowth within 27 months to 60 months. Late tumor regrowth, localized in the center, occurred in one eye after 65 and another after 69 months. One tumor was successfully replaqued; the other was not re-treated because the patient had had a recent heart attack. In 17 eyes radiation retinopathy developed after 1 1/2 years, the earliest in a diabetic eye. Despite primary recovery of preoperative vision, there was severe deterioration of visual acuity after 4 1/2 years in all the eyes. During follow up, two patients died due to metastases after 28 and 71 months; one patient is alive with metastases after 17 months. None of the eyes had to be enucleated. There was no incidence of madaurosis, symblepharon, or dry eye. PMID- 8219735 TI - Trachoma: possibilities of prevention. A study in the Sultanate of Oman. AB - Using a questionnaire and direct observation, this survey aimed at providing basic information on how to design an effective trachoma prevention campaign. Among the population of rural Oman, the causal relations between Chlamydia conjunctivitis and the later complications, trichiasis, corneal ulcer and eventually blindness, are still widely unknown, so that prevention of contagion seems irrelevant in public opinion. A booklet on the prevention of blindness was very poorly understood, because the population is highly illiterate, and because even the pictures used were not appropriate. Such concepts as contagion and the importance of flies in the spread of diseases appeared to be common in the population surveyed. These ideas could provide a starting point in a picture- and television-based campaign. The results are consistent with theory that the success of a trachoma prevention campaign depends on a thorough knowledge of local sociocultural particularities. PMID- 8219736 TI - Proteins in the subretinal fluid. AB - This study was designed to improve the understanding of the mechanisms that govern the origin of retinal detachment (RD) by examining the quantitative composition of proteins in the subretinal fluid (SRF). Inflammation proteins and immunoglobulins (Ig) were titrated from SRF and sera in 25 patients with RD The following concentrations were found in SRF: total proteins 16 g/l, albumin 12.6 g/l; pre-albumin 0.37 g/l; transferin 1.8 g/l in 68% of cases; haptoglobin and alpha 2 macroglobin were present in only one SRF: alpha 1 antitrypsin 0.86 g/l in 48%; orosomucoid 0.57 g/l in 32%; IgG 2 g/l in 52%; IgA 0.17 g/l in 88% and IgM 15.9 mg/l in 56%. Correlations were found between the duration of detachment and the concentration of total proteins (p < 0.01). The extent of RD was correlated with the concentration of IgG or IgA in the SRF (p < 0.01). These findings suggest that the correlation between the Ig concentration and the extent of RD is an argument for the participation of choriocapillaris in the genesis of SRF. PMID- 8219737 TI - Localised Wegener's granulomatosis presenting as an orbital pseudotumour with extension into the posterior cranial fossa. AB - Pseudotumour has rarely been reported to invade the intracranial cavity. We present a case of pseudotumour which extended intra-cranially into the posterior cranial fossa. The patient had circulating antineutrophil cytoplasmic antibodies in titres diagnostic for Wegener's granulomatosis. In the absence of clinical renal or respiratory tract disease, the case may represent a newly recognized sub type of "localised" Wegener's granulomatosis. PMID- 8219738 TI - Improved frequency resolution in multidimensional constant-time experiments by multidimensional Bayesian analysis. AB - The resolution of spectral frequencies in NMR data obtained from discrete Fourier transformation (DFT) along D constant-time dimensions can be improved significantly through extrapolation of the D-dimensional free induction decay (FID) by multidimensional Bayesian analysis. Starting from Bayesian probability theory for parameter estimation and model detection of one-dimensional time domain data [Bretthorst, (1990) J. Magn. Reson., 88, 533-551; 552-570; 571-595], a theory for the D-dimensional case has been developed and implemented in an algorithm called BAMBAM (BAyesian Model Building Algorithm in Multidimensions). BAMBAM finds the most probable sinusoidal model to account for the systematic portion of any D-dimensional stationary FID. According to the parameters estimated by the algorithm, the FID is extrapolated in D dimensions prior to apodization and Fourier transformation. Multidimensional Bayesian analysis allows for the detection of signals not resolved by the DFT alone or even by sequential one-dimensional extrapolation from mirror-image linear prediction prior to the DFT. The procedure has been tested with a theoretical two-dimensional dataset and with four-dimensional HN(CO)CAHA (Kay et al. (1992) J. Magn. Reson., 98, 443-450) data from a small protein (8 kDa) where BAMBAM was applied to the 13C alpha and H alpha constant-time dimensions. PMID- 8219739 TI - 3D 13C/1H NMR-based assignments for side-chain resonances of Lactobacillus casei dihydrofolate reductase. Evidence for similarities between the solution and crystal structures of the enzyme. PMID- 8219740 TI - Metropolis Monte Carlo calculations of DNA structure using internal coordinates and NMR distance restraints: an alternative method for generating a high resolution solution structure. AB - A new method, a restrained Monte Carlo (rMC) calculation, is demonstrated for generating high-resolution structures of DNA oligonucleotides in solution from interproton distance restraints and bounds derived from complete relaxation matrix analysis of two-dimensional nuclear Overhauser effect (NOE) spectral peak intensities. As in the case of restrained molecular dynamics (rMD) refinement of structures, the experimental distance restraints and bounds are incorporated as a pseudo-energy term (or penalty function) into the mathematical expression for the molecular energy. However, the use of generalized helical parameters, rather than Cartesian coordinates, to define DNA conformation increases efficiency by decreasing by an order of magnitude the number of parameters needed to describe a conformation and by simplifying the potential energy profile. The Metropolis Monte Carlo method is employed to simulate an annealing process. The rMC method was applied to experimental 2D NOE data from the octamer duplex d(GTATAATG).d(CATTATAC). Using starting structures from different locations in conformational space (e.g. A-DNA and B-DNA), the rMC calculations readily converged, with a root-mean-square deviation (RMSD) of < 0.3 A between structures generated using different protocols and starting structures. Theoretical 2D NOE peak intensities were calculated for the rMC-generated structures using the complete relaxation matrix program CORMA, enabling a comparison with experimental intensities via residual indices. Simulation of the vicinal proton coupling constants was carried out for the structures generated, enabling a comparison with the experimental deoxyribose ring coupling constants, which were not utilized in the structure determination in the case of the rMC simulations. Agreement with experimental 2D NOE and scalar coupling data was good in all cases. The rMC structures are quite similar to that refined by a traditional restrained MD approach (RMSD < 0.5 A) despite the different force fields used and despite the fact that MD refinement was conducted with additional restraints imposed on the endocyclic torsion angles of deoxyriboses. The computational time required for the rMC and rMD calculations is about the same. A comparison of structural parameters is made and some limitations of both methods are discussed with regard to the average nature of the experimental restraints used in the refinement. PMID- 8219741 TI - Application of nonlinear sampling schemes to COSY-type spectra. AB - Nonlinear sampling along the t1 dimension is applied to COSY-type spectra. The sine dependence of the time domain signals for the cross peaks is matched by a nonlinear sampling scheme that samples most densely around the maximum of the sine function. Data are processed by maximum entropy reconstruction, using a modified implementation of the 'Cambridge' algorithm of Skilling and Bryan. The procedure is demonstrated for P.E. COSY spectra recorded on a cyclic hexapeptide and on a 126-residue domain of the protein villin. The number of t1 values in the nonlinearly sampled experiments was reduced by a factor of four compared to linear sampling. The sensitivity and resolution of the resulting spectra are comparable to those achieved by conventional methods. The method described can thus significantly reduce the measuring time for COSY-type spectra. PMID- 8219742 TI - Two- and three-dimensional 31P-driven NMR procedures for complete assignment of backbone resonances in oligodeoxyribonucleotides. AB - We describe a strategy for sequential assignment of 31P and deoxyribose 1H NMR resonances in oligode-oxyribonucleotides. The approach is based on 31P-1H J-cross polarization (hetero TOCSY) experiments, recently demonstrated for the assignment of resonances in RNA [Kellogg, G.W. (1992) J. Magn. Reson., 98, 176; Kellogg, G.W. et al. (1992) J. Am. Chem. Soc., 114, 2727]. Two-dimensional heteroTOCSY and heteroTOCSY-NOESY experiments are used to connect proton spin systems from adjacent nucleotides in the dodecamer d(CGCGAATTCGCG)2 entirely on the basis of through-bond scalar connectivities. All phosphorus resonances of the dodecamer are assigned by this method, and many deoxyribose 1H resonances can be assigned as well. A new three-dimensional heteroTOCSY-NOESY experiment is used for backbone proton 4', 5' and 5" resonance assignments, completing assignments begun on this molecule in 1983 [Hare, D.R. et al. (1983) J. Mol. Biol., 171, 319]. Numerical simulations of the time dependence of coherence transfer aid in the interpretation of heteroTOCSY spectra of oligonucleotides and address the dependence of heteroTOCSY and related spectra on structural features of nucleic acids. The possibility of a generalized backbone-driven 1H and 31P resonance assignment strategy for oligonucleotides is discussed. PMID- 8219743 TI - NMR chemical shifts and structure refinement in proteins. AB - Computation of the 13C alpha chemical shifts (or shieldings) of glycine, alanine and valine residues in bovine and Drosophila calmodulins and Staphylococcal nuclease, and comparison with experimental values, is reported using a gauge including atomic orbital quantum-chemical approach. The full approximately 24 ppm shielding range is reproduced (overall r.m.s.d. = 1.4 ppm) using 'optimized' protein structures, corrected for bond-length/bond-angle errors, and rovibrational effects. PMID- 8219744 TI - Renal retention of selenium after administration of trimethylselenide. AB - Renal retention of selenium after administration of trimethylselenonium iodide (TMSeI) was studied in vivo in male and female rats during sexual maturation. The selenium level in the kidneys was found to be significantly higher in male rats than in females during the first hour after intravenous (i.v.) administration of TMSeI. The sex-linked difference, manifested already in 21-day old animals, increased markedly during the following four weeks of postnatal life. It was shown that this process may be accelerated by previously increased selenium intake. The sex-linked difference in renal retention of selenium was observed after administration of TMSeI in a wide range of doses: 0.002-10.0 mumol per animal. The size of the applied dose did not affect significantly the kinetic patterns of selenium in the kidneys during the first hour after i.v. injection. The results suggest the existence of a sex-dependent mechanism in the kidneys which may control the rate of excretion of trimethylselenonium ions in urine both under conditions of normal selenium intake and selenium intoxication. PMID- 8219745 TI - Review of publications. PMID- 8219746 TI - Ischemic heart disease: nutrition or pharmacotherapy? AB - There are many diseases of unknown etiology. Increasingly vibrant, contemporary research is attempting to associate trace element metabolism with some of these illnesses. Because trace elements can produce profound effects on health via enzymes, hormones and messenger molecules, analytical assessment must be directed toward these chemicals as well as to the trace elements. Element analysis may be directed best toward specific cells, tissues and organs. Copper deficiency is associated with the etiology, pathogenesis and pathophysiology of ischemic heart disease via metabolic processes affecting cardiovascular health. Some drugs now used to treat heart disease affect copper metabolism but many other metabolic processes are unaffected by deficiency. It seems prudent to avoid diets containing amounts of copper that have been proved insufficient for people in controlled experiments. PMID- 8219747 TI - The role of calcium in the modulation of the hepatic anti-oxidant defence system. AB - A normocalcemic animal model of vitamin D (vit. D)-deficiency has been successfully developed by feeding a high calcium (Ca2+) diet to vit. D.-deficient rats. The modulating role of Ca2+ on the hepatic antioxidant defence system and lipid peroxidation has been evaluated in this model. Partial restoration of liver function was noted in these rats following extra Ca2+ feeding. Serum alkaline phosphatase and alanine aminotransferase reverted to a normal level. The reduced levels of hepatic SOD and glutathione peroxidase in vit. D.-deficient rats, were also increased after extra Ca2+ supplementation. Even elevated lipid peroxidation due to vit. D.-deficiency was reduced after feeding the extra Ca(2+)-supplemented diet. However, catalase activity remained at the control level throughout the study. The results provide important evidence that normocalcemia is essential for maintaining the hepatic antioxidant defence and controlling lipid peroxidation in the in vivo milieu. PMID- 8219748 TI - Calcium uptake and ATPase activity of sarcoplasmic reticulum vesicles isolated from control and selenium deficient lambs. AB - The calcium uptake and ATPase activity were studied using fragmented sarcoplasmic reticulum (FSR) vesicles from normal and selenium (vitamin E)--deficient lambs. The latter group was suffering from white muscle disease (WMD). The calcium uptake of FSR vesicles from muscle of WMD lambs was reduced 10-fold as compared to those from normal lambs. An inverse relationship was found with the calcium uptake ability of the FSR vesicles and the severity of WMD. ATPase activity was nonsignificantly lower in vesicles from WMD lambs. The most active FSR vesicles from both normal and WMD lambs banded at 27% when purified on linear sucrose density gradients. The number of protein bands appearing in acrylamide gels of the purified vesicles appeared to be directly proportional to the severity of WMD. The 75Se cosedimented with the calcium uptake and ATPase activity when FSR vesicles from a lamb injected with 75Se-selenite were subjected to linear sucrose density gradient centrifugation, suggesting that selenium is incorporated into these vesicles. Injection of selenium into WMD lambs resulted in significantly greater calcium uptake activity in vesicles 18 and 38 days later as compared with untreated WMD lambs. Injection of selenium in WMD lambs resulted in a marked decrease in plasma CPK activity and a significant increase of glutathione peroxidase activity in the blood. PMID- 8219749 TI - Aluminium content of infant formulas. AB - An investigation was undertaken in order to assess Al concentration levels in infant formulas. Eligibility criteria were defined and strictly adhered to. An overall strategy was worked out to guarantee reliability and representativity of experimental data, in particular by minimizing all possible sources of chemical contamination or loss. The study was carried out by means of Inductively-Coupled Plasma Atomic Emission Spectrometry (ICP-AES). In cow's milk-based infant formulas as made up for consumption (about 13% in the final solution), Al levels of between 0.03-0.85 mg/L were detected. Higher amounts were present in soya based formulas, with concentrations ranging from 0.39 to 1.01 mg/L. PMID- 8219750 TI - Effect of time on neonatal immune response to dietary selenium and fat. AB - The effect of dietary selenium (0.03 mg/kg and 0.31 mg/kg), and fat (5% and 20% corn oil) on antibody formation in the neonatal rat was studied at two different time periods using four diets. The latter were fed to dams throughout pregnancy and lactation and to their pups starting at day 18. A week later, pups received intraperitoneal injections of the test antigen, fluorescein-bovine serum albumin in complete Freund's adjuvant (150 micrograms per 30 g body wt.). On days 7 or 9 post-injection, the pups were sacrificed. The antibody titer, as determined by the quenching of fluorescein by the test sera, and by ELISA, almost doubled from day 7 to day 9 (p < 0.05). There was no significant difference in antibody titers between dietary groups except at day 9 post-injection. Using ELISA, pairwise comparisons indicated that addition of 0.3 mg/kg Se to high fat diet was associated with low antibody titer (p < 0.05). PMID- 8219751 TI - On the capacity of the rat intestine to excrete lithium ions at therapeutic and toxic plasma lithium concentrations. AB - Lithium (Li) excretion into the intestinal lumen was quantitated in rats in situ by use of a pendular perfusion technique. Male Sprague-Dawley rats were injected daily (7-10 days) i.p. with 1, 3, and 6 mmol LiCl per kg body weight (n = 9-12). Jejunal as well as ileal and colonic segments were perfused with isotonic saline containing 3H-PEG-4000. Perfusate samples were taken after 0, 5, 10, 20, and 60 min. At the highest dose toxic symptoms were observed. At 6 mmol Li per kg the plasma Li concentrations were higher than those linearly extrapolated from the lower-dose groups, which may be due to inappropriate renal excretion. The Li concentration in the perfusate increased linearly over time and was not significantly different between jejunal and colonic segments. The same ratio between the Li concentration in the plasma and in the luminal perfusate was observed in all groups. Intestinal Li excretion is not impaired by high plasma concentrations. The intestinal capacity to excrete Li is considerable: 45 cm of jejunum is able to excrete the intire plasma Li content in 30-40 min, when Li is not resupplemented from intracellular stores. The renal clearance of lithium (Li) decreases when toxic Li plasma concentrations are reached. Therefore, if it were possible to trap Li in the intestinal lumen, this excretion route might be of therapeutic interest in cases of Li intoxication with impaired renal Li excretion. PMID- 8219752 TI - The diagnosis and treatment of malignant melanoma with special reference to neutron capture therapy. PMID- 8219753 TI - Diagnosis and treatment of malignant melanoma. Presentations made at the Melanoma Symposium of the 18th World Congress of Dermatology. New York, 12-18 June 1992. PMID- 8219754 TI - Cell-cell and cell-extracellular matrix interactions during melanoma cell invasion and metastasis. AB - Although great advances have been made in recent years in understanding the interactions between tumour cells and their environment, we still do not fully understand the complex mechanisms involved in the steps by which in situ malignancy becomes invasive and then metastatic. To complete the various steps of the pathway to metastatic malignancy, melanoma cells have acquired the ability to grow in the absence of certain growth factors while producing autocrine factors. They are also able to modulate the extracellular matrix and express an array of adhesion molecules enabling them to interact with various cell types and extracellular matrix molecules during the establishment of secondary tumours. PMID- 8219755 TI - Adhesion molecule profile and malignancy of melanocytic lesions. AB - The ability of melanoma cells to metastasize is largely dependent upon cell surface molecules that mediate cell-matrix and cell-cell interactions. Our aim was to investigate the expression of such molecules (adhesion molecules) on tissue sections of a series of melanocytic lesions in different stages of tumour progression. Four common naevi, four congenital naevi, four dysplastic naevi, three Spitz naevi, 20 primary melanomas and 15 metastatic melanomas were tested with an alkaline phosphatase/anti-alkaline phosphatase technique and a panel of monoclonal antibodies directed toward different alpha subunits of VLA receptors, beta 1, VNR-alpha and beta 3 subunit, and CD44 hyaluronate receptor. Only metastatic melanomas expressed the alpha 4 subunit, and only thick primary melanomas and metastases expressed the beta 3 subunit. The alpha 6/beta 1 chain was expressed at significantly higher levels on benign lesions, and a trend towards increased expression of alpha 2 and alpha 3 subunits was found in malignant versus benign lesions. Our results show that the pattern of integrin expression changes in melanocytic lesions along with malignant transformation. PMID- 8219756 TI - Decreased expression of human melanoma-associated antigen ME491 along the progression of melanoma pre-canceroses to invasive and metastatic melanomas. AB - ME491 expression was examined by immunohistochemistry in the different stages of various types of human malignant melanomas. In addition, the primary and metastatic lesions in five patients were studied to compare the ME491 antigen expression between these lesions in a single patient. A large proportion of cells from melanoma pre-canceroses showed strong ME491 expression, whereas the proportion of negatively stained tumour cells increased in the melanomas invading the dermis and in metastatic melanomas. In addition, a comparison of five sets of primary tumour and its metastatic lesion revealed decreased expression of this antigen in metastases. These results show that the reduction or loss of ME491 antigen expression is associated with increased invasiveness and metastatic ability of human malignant melanoma, suggesting that ME491 may act as an anti metastatic gene. PMID- 8219757 TI - Organ-specific metastases in immunodeficient mice injected with human melanoma cells: a quantitative pathological analysis. AB - Pathological and morphometric techniques were used to investigate the potential of two human melanoma cell lines for organ colonization in three different immunodeficient mouse strains; nude (nu/nu), NIH triple immunodeficient (TID: nu/nu, bg/bg, xid/xid) and severe combined immunodeficient (SCID) mice. The MM-RU cell line gave rise exclusively to lung metastases, whereas the MM-AN cell line gave rise to lung and extrapulmonary metastases. Although the TID mice showed more pancreatic and brown fat lesions than nude or SCID mice, the overall pattern of distribution of organ metastases among the strains was similar, suggesting that cellular properties intrinsic to the melanoma cells are important for the colonization of specific organs. The metastatic nodules were well circumscribed in all organs and exhibited peripherally located macrophages, except for brain metastases, where a more invasive pattern along vasculature was observed. The differences in cellular infiltrate and infiltrative patterns of the tumors implicate features of the host microenvironment (organ-specific factors) which are, at least in part, independent of the host's genetic background or degree of immunodeficiency. Our findings suggest that intrinsic malignant cellular properties play an important role in organ-specific colonization by haematogenously metastasizing cells. PMID- 8219758 TI - Regulatory factors for polymerization of melanin monomers within coated vesicles and premelanosomes in melanoma cells. AB - Coated vesicles (CV) and premelanosomes (PMS) differ in the amount of melanin monomers produced from 2-carboxy-2,3-dihydroindole-5,6-quinone (dopachrome) in vitro. CV convert dopachrome preferentially to 5,6-dihydroxy-indole-2-carboxylic acid (DHI2C) and PMS mainly to 5,6-dihydroxyindole (DHI). We examined the effect of CV and PMS on in vitro spontaneous polymerization of DHI and DHI2C. The polymerization of DHI is accelerated by addition of extracts from both CV and PMS, while polymerization of DHI2C is suppressed. Factors associated with these two regulatory activities have been separated on concanavalin A-Sepharose. The ConA-adhesive glycoproteins isolated from PMS enhance polymerization of not only DHI but also DHI2C. The latter effect is stimulated by dopa. Both accelerating activities can be inhibited by phenylthiourea (PTU). In contrast to glycoproteins, the non-glycoprotein subfraction suppresses spontaneous polymerization of both melanin monomers. Our data suggest that the absence of in vivo melanin polymer formation within CV can be explained by formation by these organelles of relatively stable DHI2C rather than easily polymerizing DHI. PMID- 8219759 TI - cDNA-based functional domains of a calnexin-like melanosomal protein, p90. AB - We have recently identified a gene encoding a calnexin-like protein (p90) by the immunoscreening of a human melanoma cDNA library, using a rabbit anti-human melanosomal antibody. This p90 protein was highly expressed by human melanocytes and associated with melanosomal membrane and endoplasmic reticulum. In this study we report the computer analysis of the predicted amino acid sequence of this calnexin-like melanosomal protein. We found that p90 is a membrane-bound protein whose large N-terminal domain is located within the melanosomal compartment; its shorter C-terminal is exposed to the cytosol and separated by a short transmembrane region. This p90 protein was found to have consensus sequences of a Ca(2+)-binding loop and a protein kinase C phosphorylation site at the N-terminal domain. The C-terminal domain, on the other hand, contained sequences of a casein kinase II phosphorylation site and two protein kinase A phosphorylation sites. Such functional motifs could provide signal transduction across the melanosomal membrane, the reception of melanogenic protein via carriers at the melanosomal membrane and the translocation of melanosomes in the melanocyte. PMID- 8219760 TI - Linkage analysis in Dutch familial atypical multiple mole-melanoma (FAMMM) syndrome families. Effect of naevus count. AB - Familial atypical multiple mole-melanoma (FAMMM) syndrome is characterized by the familial occurrence of malignant melanoma of the skin in combination with multiple atypical precursor naevi. In the present study we performed linkage analysis in seven Dutch FAMMM families to define the relationship between the ultimate phenotype melanoma and the postulated precursors, atypical (dysplastic) naevi. Various models were defined, varying from melanoma only to various combinations of melanoma and atypical naevi, reflecting the FAMMM phenotype. Using 124 microsatellite markers spread across all autosomes, hints for linkage were obtained between several chromosome 9p markers and a melanoma locus (D9S171; odds for linkage, 275:1). In a model including melanoma and a florid manifestation of atypical naevi a considerably higher lod score was obtained with D9S171 (odds for linkage, 4365:1); models including milder manifestations yielded less support. We conclude that, also in the Dutch FAMMM families, a melanoma gene is located on the short arm of chromosome 9 and that multiple atypical naevi, at least in certain cases, seems to be a component of the FAMMM phenotype. PMID- 8219761 TI - Early recognition and prognostic markers of melanoma. AB - Malignant melanoma can be cured if the tumour is recognized at an early phase. Therefore, early recognition is of critical importance and cannot be overemphasized. Epiluminescence microscopy is a non-invasive technique that makes sub-surface structures of skin accessible for in vivo microscopic examination and thus provides additional criteria for the diagnosis of pigmented skin lesions. Thereby preoperative clinical diagnosis can be improved. In order to assess the prognosis of a melanoma patient and to predict the outcome of the disease a number of morphological and immunological parameters these will be reviewed, are helpful. PMID- 8219762 TI - Modulation by MHC class I antigens of the biology of melanoma cells. Non immunological mechanisms. AB - Many human as well as experimental tumours, including melanoma, express reduced levels of major histocompatibility complex (MHC) Class I antigens. Decreased MHC Class I antigen expression may be selected during neoplastic progression because it allows tumour cells to escape killing by cytotoxic T lymphocytes. Furthermore, the regulatory role of MHC Class I antigens in the proliferation of T cells suggests that abnormalities in MHC Class I antigen expression may play a role in the disordered proliferation of malignant cells and in their metastatic potential by non-immunological mechanisms. This paper reviews some of the available evidence supporting the concept of non-immune functions of MHC Class I antigens in the biology of malignant cells, with emphasis on experimental models for metastatic melanoma. PMID- 8219769 TI - Depression and SGI: are you driving legally? PMID- 8219770 TI - Ethnic/movement dance: therapeutic intervention for psychiatric clients. PMID- 8219771 TI - Canadian Mental Health Association: Partnership for change: taking responsibility. PMID- 8219772 TI - Family matters: Chilly Willy days. PMID- 8219773 TI - Rheumatoid factor: primary or secondary event in the pathogenesis of RA? AB - Rheumatoid factors have been recognised and studied for over fifty years. They are anti-IgG immunoglobulins which occur in most patients with rheumatoid arthritis. Their precise contribution to the pathology of this disease however remains an enigma, since they are also demonstrable in other autoimmune and infectious diseases, as well as in normal healthy controls. Thus the importance of RF in RA may not pertain merely to their presence, but to the nature of the autoantibodies themselves. RF in RA are found to differ from those in control subjects and in other diseases such Waldenstrom's macroglobulinaemia in terms of their binding affinities for IgG, subclass specificity and V gene usage. The role of RF as either the initiating factor or its occurrence as a secondary event in RA is discussed. PMID- 8219775 TI - Age-related changes in the expression of IL-2 and high-affinity IL-2 binding sites. AB - T cell responsiveness to in vitro stimulation is severely diminished in the aged. Recent studies would suggest that this may be due, at least in part, to a reduction in interleukin 2 (IL-2) secretion and high-affinity IL-2 receptor (HA IL-2R) expression. In this report we confirm and extend these studies to show that the fall in IL-2 production is not due to reduced numbers of IL-2 mRNA producing T cells but rather to a decline in the relative amount of IL-2 mRNA expressed per cell. Although we found an age-related reduction in the number of high-affinity binding sites on phytohaemagglutinin-activated T cell blasts by ligand-binding studies, we did not observe alterations in the number of cells that expressed both chains of the HA-IL-2R by two-colour immunofluorescence using monoclonal antibodies specific for p55 (alpha) chain and p75 (beta) chain. However, we did observe a substantial diminution in the number of activated T cells expressing p55 alone in the aged. Given that IL-2 upregulates p55 expression and is involved in the formation of HA-IL-2R, our results suggest that defective IL-2 expression is the primary lesion in age-related T cell senescence. PMID- 8219774 TI - Role of the membrane attack complex of complement in lung injury mediated by antibodies to endothelium. AB - The potential pathogenic role of the membrane attack complex (MAC) of the complement system was investigated in two models of lung injury mediated by antibodies to angiotensin-converting enzyme (ACE), an endothelial cell enzyme. In the first model, acute and fatal lung edema was induced in rabbits by intravenous administration of divalent anti-ACE antibodies. These animals died acutely. C6 deficient rabbits tolerated anti-ACE antibodies without apparent ill effects. On the other hand, C6-deficient rabbits reconstituted with C6 and then receiving anti-ACE antibodies developed acute pulmonary edema and died. These results indicate that the MAC is required for the pathogenesis of this lung injury. In the second model, intravenous administration of monovalent anti-ACE Fab fragments over 4 consecutive days induced fatal interstitial pneumonitis in normal rabbits. For C6-deficient rabbits there was a reduced inflammatory response, and no animals died, implicating a mediator function for the MAC in this model as well. These results demonstrate that MAC is an important mediator of acute pulmonary edema induced by divalent antibodies to an endothelial antigen. Moreover, the complement system was also, to some extent, involved in the recruitment of inflammatory cells leading to the development of interstitial pneumonitis in the experimental lung injury induced by monovalent anti-ACE Fab fragments that 'per se' do not activate complement. PMID- 8219776 TI - Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease. AB - Previous studies in our laboratory demonstrated an altered immuno-endocrine feedback communication via the hypothalamo-pituitary-adrenal (HPA) axis, which may be an important modulatory factor in the development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens. These birds show a significantly lower, or even absent, increase in serum glucocorticoid levels in response to an intravenous injection of antigen or conditioned medium (CM) from mitogen-stimulated spleen cells known to contain glucocorticoid-increasing factors (GIFs), notably interleukin-1 (IL-1). The present study was aimed at investigating this feedback regulation in animal models with spontaneous systemic autoimmune diseases, such as the UCD-200 chicken, which serves as a model for human scleroderma, and various murine lupus models. In contrast to OS chickens, UCD-200 chickens displayed a nearly normal plasma corticosterone surge in response to CM, and IL-1 was again identified as the primary GIF in CM. Recombinant IL-1 also induced a drastic increase in plasma corticosterone levels in various strains of normal mice. A similar increase was observed in the bacterial lipopolysaccharide-resistant C3H/HeJ strain, thus excluding the possibility of bacterial endotoxin contamination. However, in young lupus-prone (NZB/W)F1 and MRL/MP-lpr mice, a significantly lower increase in plasma corticosterone levels was observed after injection of recombinant IL-1, suggesting a deficient immuno-endocrine communication via the HPA loop in this instance as well. Detailed studies to identify further cytokines with GIF activity in the avian and murine systems showed that both IL-6 and tumor necrosis factor-alpha could induce increased plasma corticosterone levels in mice, but not in chickens. IL-3, IL-8, transforming growth factor-beta, interferon-gamma and granulocyte-macrophage colony-stimulating factor were devoid of GIF activity in both chickens and mice. PMID- 8219777 TI - Effect of GM-CSF on TNF-alpha and IL-1-beta production by alveolar macrophages and peripheral blood monocytes from patients with sarcoidosis. AB - Sarcoidosis is a systemic granulomatous disorder of unknown origin characterized by activated T-lymphocytes and macrophages. Macrophage/monocyte-derived cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) have been shown to be involved in the pathogenesis of sarcoidosis. Although the production of TNF-alpha and IL-1 by alveolar macrophages (AM) and peripheral monocytes (PM) in response to lipopolysaccharide (LPS) in sarcoidosis has been well demonstrated, the production of these cytokines in response to granulocyte macrophage colony-stimulating factor (GM-CSF) has not been delineated. The present studies were designed to examine the regulatory effect of GM-CSF on TNF alpha and IL-1 beta production by AM and PM from patients with pulmonary sarcoidosis. Amounts of TNF-alpha and IL-1 beta in the culture supernatants of unstimulated AM from patients with sarcoidosis were significantly higher than those from normal subjects, whereas, there was no difference in the amounts of TNF-alpha and IL-1 beta in the culture supernatants of PM between patients with sarcoidosis and normal subjects. The amounts of TNF-alpha and IL-1 beta in the culture supernatants of GM-CSF or LPS-stimulated AM and PM were significantly higher than those of similarly stimulated AM and PM from normal subjects. This hyperresponsiveness of AM and PM to GM-CSF in patients with sarcoidosis might be relevant to the pathogenesis of sarcoidosis. PMID- 8219778 TI - Characterization of recombinant bet vI, the major pollen allergen of Betula verrucosa (white birch), produced by fed-batch fermentation. AB - The gene encoding the major allergen, Bet v I, from Betula verrucosa (white birch) pollen was cloned by application of the polymerase chain reaction with double-stranded cDNA as template and specific primers based on the published nucleotide sequence of the gene. The gene was inserted into plasmid pKK223-3 and expressed in Escherichia coli K-12 strain JM105 grown to high cell density in a fermenter using a fed-batch procedure. Ample material was provided for a thorough characterization of the epitope structure of recombinant Bet v I contained in an unpurified soluble lysate. The antibody-binding characteristics of recombinant Bet v I was compared with that of the natural allergen using polyclonal rabbit antibodies raised against Bet v I in crossed immunoelectrophoresis, tandem crossed immunoelectrophoresis, and Western blotting. IgE from a pool of 16 allergic patients' serum was applied in crossed radioimmunoelectrophoresis, Western blotting, and a quantitative luminescence inhibition immunoassay. Well defined epitopes were assayed by the application of a panel of six murine monoclonal antibodies in a quantitative radio inhibition immunoassay. In all assays the activity of recombinant Bet v I was comparable to that of natural Bet v I, and it is concluded that the epitope structure of recombinant Bet v I closely resembles that of natural Bet v I. This result has important implications for the future use of recombinant tree pollen allergens as a model system for the study of allergenic B and T cell epitopes aiming at improvements in reagents used for the management of allergic disease. PMID- 8219779 TI - Purification and characterization of Alt a-29 from Alternaria alternata. AB - A major protein component reactive with pooled human atopic sera was isolated from a lyophilized broth extract of Alternaria alternata 34-016. By successive chromatography on Whatman DE-52, Sephadex G-100 and Mono Q HR5/5, a low molecular weight antigen was obtained. Comparison with standard proteins on Sephadex G-100 indicated its molecular weight was 31 kD. Non-reduced samples run on SDS-PAGE showed a band at 29.2 kD which reacted strongly with human IgE. After reduction, it produced a doublet pattern on SDS-PAGE with MW 14.5 and 16.0 kD. The doublet pattern was confirmed by Western blotting with pooled human atopic sera. IEF of the protein showed a major component with a PI of 4.15 and two minor components at 4.25 and 4.40. Immunoblots of the IEF bands showed all three were reactive with human IgE. Ion exchange chromatography of the protein on Mono Q HR5/5 resulted in three resolved components, all of which are immunoreactive. Together with the IEF data, this suggests that there are several conformational or structural isoforms of this protein. PMID- 8219780 TI - Suppression of murine IgE responses with ovalbumin-pullulan conjugates: comparison of the suppressive effect of different conjugation methods and different molecular weights of pullulan. AB - Ovalbumin (OVA)-pullulan conjugates were made using four different conjugation methods and eight different molecular weights of pullulan ranging from 4,200 to 600,000. Pretreatment of mice by the administration of conjugates made by using cyanulic chloride or cyanogen bromide and pullulan of molecular weight 40,000 or more, anti-OVA IgE antibody response was suppressed completely and anti-OVA IgM and IgG antibody response was enhanced. In contrast, by the administration of conjugates made by using an oxidation or thiol activation method, only partial suppression of anti-OVA IgE antibody response was achieved and no enhancement of anti-OVA IgM and IgG antibody production was observed. PMID- 8219781 TI - Isotypic analysis of grass-pollen-specific immunoglobulins in human plasma. 2. Quantification of the IgE, IgM, IgA class and the IgG subclass antibodies. AB - Previously, the specificity of human immune responses to Dactylis pollen was analyzed in 26 plasma samples with high levels of grass-pollen-specific IgG4 ('IgG4+ plasma', largely from grass-pollen-allergic patients), as compared to 25 plasma samples with low grass-pollen-specific IgG4 ('normal plasma', from nonatopic individuals). In the present study, a quantification of the Dactylis pollen-specific IgE, IgM, IgA class and IgG subclass antibodies in these plasma samples is proposed. Isotypic distribution in IgG4+ plasma was 68% IgG [IgG2 (38%) > IgG4 (30%) > IgG1 (19%) > IgG3 (13%)], 27% IgM, 4% IgA and 0.05% IgE. In normal plasma it was 73% IgM, 20% IgG [IgG3 (38%) > IgG2 (33%) > IgG1 (29%) > IgG4 (0%)], 6% IgA and 0.006% IgE. In IgG4+ plasma, specific IgE, IgG1, IgG2 and IgG4 concentrations were positively correlated between each other. Finally, the present study clearly confirmed the possible role of the CH gene regulation in allergic diseases. PMID- 8219782 TI - Detection of IgE antibodies specific for allergens in cow milk and cow dander. AB - Sera from patients with cow milk protein allergy (n = 6) and cow dander allergy (n = 5) were analyzed for reactivity of IgE antibodies specific for allergens derived from milk and cow dander. The cow milk- and cow dander-allergic patients exhibited elevated specific IgE levels to milk and to cow dander, respectively, as determined by RAST. IgE immunoblot analysis revealed that cow milk-allergic patients exhibited IgE binding to the milk allergens casein, beta-lactoglobulin, alpha-lactalbumin and bovine serum albumin. Four of six cow milk-reactive patients also exhibited IgE binding to cow dander proteins with molecular weights of 20, 22, 36, 50 and > 200 kD. IgE from the sera of cow dander-allergic patients reacted with the major allergens of cow dander (20 and 22 kD) and with other proteins with molecular weights of 24, 36, 42, 50 and 70 kD. Only one out of five of these sera displayed IgE reactivity with cow milk proteins with molecular weights of 69, 92 and > 200 kD. Inhibition studies revealed the cross-reactive nature of the IgE antibodies. Preincubation of cow milk-positive sera with cow milk and subsequent immunoblotting led to complete blocking of IgE binding to cow dander proteins and to cow milk proteins. Preincubation of cow milk-positive sera with cow dander extract led to blocking of IgE binding only to defined cow milk proteins: these could be identified in 2 cases as casein and in 1 case as beta lactoglobulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219783 TI - Mechanisms of bronchoconstriction after allergen ingestion in sensitized guinea pigs. AB - We examined whether oral administration of allergen induced bronchoconstriction in sensitized guinea pigs and investigated the mechanisms of bronchoconstriction. The animals had been immunized intraperitoneally with a mixture of Ascaris suum extract and silica gel, and exposed to ozone. They were then challenged with an oral dose of A. suum extract (6 mg/kg), and respiratory resistance (Rrs) was measured up to 7 h. After oral administration of the allergen, an increase in Rrs was observed. The mean values at 1, 3, 5 and 7 h after oral allergen challenge were 150 +/- 21, 149 +/- 11, 151 +/- 12 and 134 +/- 10% of the baseline value, respectively. When saline instead of the allergen was orally administered, almost no significant increase in Rrs was observed up to 7 h. Moreover, in nonsensitized guinea pigs, oral administration of allergen produced no significant increase in Rrs for up to 7 h. When atropine was administered as an aerosol, the increase in Rrs induced by an oral allergen challenge was attenuated. Three of the five atropine-treated guinea pigs showed temporary increases in Rrs immediately after the oral allergen challenge. The mean values of Rrs in the atropine-treated animals challenged with oral allergen at 1, 3, 5 and 7 h were 106 +/- 3, 106 +/- 5, 115 +/- 5 and 102 +/- 4% of baseline value, respectively. In the animals which received oral allergen, the number of neutrophils in bronchoalveolar lavage fluid (BALF) significantly increased 2.0-fold (p < 0.05), while no significant increase in the number of eosinophils, macrophages, or lymphocytes in BALF was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219784 TI - Aeroallergen sensitization can occur during fetal life. AB - Umbilical cord blood lymphocytes showed consistent proliferation in response to Dermatophagoides group I (Der p I) and occasionally even to Lolium group I (Lol p I) allergen. These data suggest sensitization in utero of T cells due to inhalation of these allergens by the mother during pregnancy. PMID- 8219785 TI - Chronic neutropenia associated with C2 and C9 deficiency. AB - A Japanese male with a deficiency of the second and ninth components of complement associated with chronic idiopathic neutropenia is presented. In this case the second component of complement is totally deficient while the ninth component is approximately half that of normal control. Neutrophil granulocytes are constantly few, but this case shows no evidence of susceptibility to either viral or bacterial infections. His HLA type is different from that of Caucasians, suggesting that the genetic abnormality responsible for the complement deficiency of this Japanese case is different from that seen in Caucasian patients. PMID- 8219786 TI - Allergic granulomatosis and angiitis (Churg-Strauss vasculitis) in pregnancy. AB - Allergic granulomatosis and angiitis is very rare in pregnancy. To the best of our knowledge, no such case has been reported in the English literature up to now. We describe a patient who developed multisystem disease with mononeuritis multiplex, dermal vasculitis, and pleuritis during gestation with an excellent response to therapy and a good pregnancy outcome. PMID- 8219787 TI - [Epidemiological features of retroviral infection by HTLV-1 in central Africa]. AB - Subsaharian Africa is the most important reservoir of HTLV1 virus but its epidemiology is not well-known. The authors have studied from 1987 to 1990 the situation in 6 countries in Central Africa. The already described routes of transmission are present: through blood transfusions (but it's not such a common practice), heterosexual transmission (but it doesn't seem to be as important as in other continents), and mother to child transmission through breast feeding. Nevertheless, environmental factors--which have to investigated--could play a role for transmission, among them one could think to vectors and parasites. PMID- 8219788 TI - [Chromobacterium violaceum, opportunist pathogenic bacteria in tropical and subtropical regions]. AB - Chromobacterium violaceum is isolated from soil and waters in tropical and subtropical areas. This Gram negative bacillus is considered as a saprophyte, but occasionally it can act as an opportunistic pathogen for animals and man, and cause fatal septicaemia from skin lesion with many liver and lung abscesses. Classification, nomenclature, media used to isolation, characters useful to identification (morphology, cultural and biochemical traits, violacein pigmentation), differentiation from related violet-pigmented species and from Vibrionaceae (when C. violaceum cultures are not pigmented), antibiotics resistance and susceptibility, experimental and natural pathogenicity are emphasized. PMID- 8219789 TI - [Apropos of 1 case of ophthalmologic manifestation of bilharziasis]. AB - We present an ocular manifestation of schistosomiasis. We observed the case of a 10 year old young girl living near a flooding canal of the Niger river. She presented a tumor of the left lid associated with an important ptosis. This tumor resulted from numerous polyps of the conjunctiva. The histological analysis of a biopsy of the conjunctiva made the diagnostic. It was confirmed by the analysis of urine and by the important amelioration of inflammation resulting from a specific therapy. PMID- 8219790 TI - [Piroplasmosis transmission in mammals. Epidemiological and prophylactic consequences]. AB - The author analyses the nosological complex "piroplasmosis" and emphasizes the differences between the two sub-orders and families of "piroplasms". He studies the life-cycle of these parasites in mammals and in their vectors, acari belonging to the super-family Ixodoidea. He lays out the mechanisms of piroplasmosis transmission to animals and, sometimes, to man and draws from these data the epidemiological features and means of control. PMID- 8219791 TI - [Seroprevalence of rubella in 461 pregnant women in Abidjan (Cote d'Ivoire)]. AB - The authors report the results of a seroepidemiological study of rubella in pregnancy. Rubella antibodies were present in 82% of the pregnant women and 18% were seronegative. Most of seronegative women were less than twenty years old, nulliparous, on first period of gestation and in low socioeconomical conditions. PMID- 8219792 TI - [Prevalence of superficial mycoses in an urban ecosystem in Sfax (Tunisia)]. AB - The authors studied the epidemiological aspects and the frequency of the various etiological agents of the superficial mycosis found in the region of Sfax, from 1,724 mycologic samples collected during 3 years (1989-1991). The rate of positivity is of 49%. The anthropophile dermatophytic species are often isolated dominated by the Trichophyton rubrum and the Trichophyton violaceum. The fungus of Candida albicans type and Malassezia furfur are the most frequently identified. The frequent localisations are the athlete foot and the onychomycosis where the rate of positivity is beyond 60%. The tinea of scalp are about to 77% due to Trichophyton violaceum, and sporadic form of tinea favosa have been described. PMID- 8219793 TI - [Non-typhoid Salmonella in pediatric patients in Tunis (Hospital Charles-Nicolle) from 1980 to 1991]. AB - 252 nontyphoidic salmonellae strains isolated from pediatrics were identified by using standard laboratory procedures and were serotyped with commercial antisera. Antibiotic susceptibility tests were performed by the agar diffusion method. Mostly isolates obtained from feces (182) and blood (67) and 89% of them from newborns and nursings. S. ser. Wien represented 75% of the isolates. The other serovars were essentially S. ser Typhimurium, S. ser Infantis and S. ser Enteritidis. All the isolates of S. ser Wien and S. ser Typhimurium were resistant to amoxicillin, carbenicillin, cephalothin, streptomycin, chloramphenicol and tetracycline from 1980. From 1987 S. ser Wien isolates developed resistance to cefotaxime and amikacin. Distribution nontyphoidic salmonellae strains according to the year was variable. Maximal isolates were in September and October. Two major epidemics were observed in this study, in 1982 and 1989. 94% of the strains determined nosocomial infections. The source of infection was established during the epidemic of 1989. The application of hygiene measures led to decline the number of isolates in 1990 and their disappearance in 1991, any strains of S. ser Wien was isolated. PMID- 8219794 TI - [Stillbirths at the regional center hospital of Sokode, Togo]. AB - 129 stillbirth cases out of 1,231 deliveries corresponding to a frequency of 104.79 out of 1,000 births have been gathered in ten months of obstetrical activity in the regional hospital of Sokode. It is a growing frequency. The main risk factors are: The poor process even the carelessness of the prenatal consultations and the per-partum survey. Almost half the pregnancies have been followed up. The foetal per-partum death rate is 65.12%. The delivery at home: 19.38%. The reduction of the still-birth frequency depends on a popular action involving both the decision-makers of the population's health and the collectivity. PMID- 8219795 TI - Molecular characterization of hepatitis C and E viruses. AB - The molecular features of each of the major viruses of non-A, non-B hepatitis, namely hepatitis C virus (HCV) and hepatitis E virus (HEV) are briefly described. The organization of the genome of each of these viruses is discussed and compared to those of other related or distantly related viruses that contain single stranded, positive-sense RNA genomes. HCV has been tentatively classified as a separate genus within the Flaviviridae, whereas HEV has been loosely associated with caliciviruses and subsequently assigned to the Caliciviridae, although it does possess unique genetic features not found in other caliciviruses. PMID- 8219796 TI - Borna disease virus: nature of the etiologic agent and significance of infection in man. AB - This review presents data on the characterization of Borna disease virus (BDV) and its potential as a possible causative agent in humans. The isolation of: (i) BDV-specific cDNA clones that encode various BDV-specific proteins and (ii) partially purified virus particles led to the conclusion that the viral genome consists of negative-sense, single-stranded RNA. The organization of the BDV specific RNA species appears to be a nested set of overlapping subgenomic RNA transcripts. Furthermore, evidence is presented that BDV can infect humans and may cause certain psychiatric and neurological disorders. This concept is supported by: (i) the finding of virus-specific antibodies in sera of patients with neuropsychiatric diseases and (ii) results obtained during attempts to isolate BDV or a BDV-related agent from the cerebrospinal fluid of seropositive patients. PMID- 8219797 TI - Biology and neurobiology of Borna disease viruses (BDV), defined by antibodies, neutralizability and their pathogenic potential. AB - Borna disease viruses (BDV) isolated from more than 20 naturally infected horses, 2 sheep and a possible feline isolate were included in these studies. Most of these wild-type viruses were grown in rabbit cells. Specifically rabbit-adapted viruses establish persistent infection in immortalized cell lines of various animal species. Brain-, tissue culture-, and cell-free released viruses could all be neutralized with antibodies from naturally and experimentally infected animals (horse; hamster, rat, rabbit, mouse, and chicken), with highest titres in birds. Splenectomized rabbits, which were subsequently infected with BDV, efficiently produced high titres of neutralizing antibodies. All of the neutralizing sera and cerebrospinal fluids from infected animals inhibited tissue culture spread of BDV. Experimental infection and hyperimmunization induced antibodies directed against the major components of the soluble antigen (60, 40/38, 25 and 14.5 kD proteins). Analysis of the s-antigen complex with these sera and 6 stable monoclonal antibodies revealed that it consists of 40/38 and 25 kD proteins. Although each of these antibodies detected intracellular virus-specific structures they did not recognize outer plasma membrane antigens, showed no cross reactivity, and had no neutralizing capacity. Unifying pathogenetic concepts of this neurotropic virus and its structural elements are discussed. PMID- 8219798 TI - Pathogenesis of Borna disease. AB - Borna disease represents a unique model of a virus-induced immunological disease of the brain. Naturally occurring in horses and sheep, the mechanisms of pathogenesis have been studied in experimental animals, namely in the rat. Many investigations have revealed that the infection of the natural hosts principally follows the same pathogenic pathways as observed in rats, leading to a severe encephalomyelitis. This affliction of the central nervous system results in severe neurological disorders that again, are fully comparable in laboratory animals to those in the natural and the different experimental hosts. In addition, alterations have been reported which are also based on the infection of the brain and do not result in the classical encephalitic clinical picture but rather in alterations of behavior. However, to all of our knowledge, the various clinical pictures of Borna disease are not caused by the infecting virus itself but rather by the hosts immune response towards it, i.e. by a virus-induced cell mediated immunopathological reaction. The importance of virus-specific CD4+ T cells as exemplified by a cultured T cell line and of CD8+ T cells as shown by immunomodulatory substances and specific antibody treatment in vivo for the pathogenesis of acute Borna disease will be elucidated here. In addition, evidence will be provided that virus-specific CD8+ T cells are also responsible for the dramatic brain atrophy in the chronic phase of the disease in rats. Therefore, Borna disease not only lends itself exquisitely well to the study of the pathogenesis of an immunopathological disease of the brain but also represents one of the few models for immune-mediated tissue destruction that eventually leads to brain atrophy and clinically to dementia. PMID- 8219799 TI - Molecular organization and replication of hepatitis E virus (HEV). AB - The recently characterized fecal-orally transmitted agent of hepatitis E (formerly known as enterically transmitted non-A, non-B hepatitis) has been determined to be a new type of positive strand RNA virus. The complete sequencing of four different geographic isolates of the hepatitis E virus (HEV) has confirmed a similar genetic organization not previously recognized in nonenveloped positive strand RNA viruses. The approximately 7.5 kb RNA genome (including polyA tail) has nonstructural genes located at the 5' end and structural genes at the 3' end. Expression of these viral genes occurs in at least 3 different forward open reading frames. The largest open reading frame begins 27 nucleotides (nt) downstream of the apparent noncoding 5' end and extends 5,079 nt. Multiple nonstructural gene motifs/domains have been recognized in this 5' ORF1 including a methyltransferase, a papain-like protease, a helicase and the RNA-dependent, RNA polymerase. The second major ORF2 begins 37nt downstream of ORF1 and extends 1980 nt before terminating 65 nt upstream of the polyadenylation site. A third ORF of only 369 nt was identified by immunoscreening experiments as encoding an immunogenic epitope of the virus. Expression of the downstream ORF2 may occur through internal subgenomic RNA initiation at a sequence element found to have homology to internal RNA initiation sequences in Sindbis virus. This element in the HEV genome maps near the apparent 5' end of one of two identified subgenomic messages. The genomic organization and expression of HEV will be discussed and a hypothesis presented regarding the viral replication strategy. PMID- 8219800 TI - Brain cell lesions in Borna disease are mediated by T cells. AB - Experimental Borna Disease (BD) in rats is characterized by severe lymphocytic encephalitis and by massive brain cell lesions finally leading to brain atrophy. Treatment of BDV-infected rats with monoclonal antibodies directed against CD4+ and CD8+ T cells could almost completely inhibit the immunopathological reactions and revealed less BDV-infected neurons and astrocytes that expressed MHC class I antigen. Brain cell lesions were minimal, and no obvious brain atrophy could be observed even late after infection. Since BDV itself is not known to exert cytopathic effects and since brain cell damage was independent of antibody titers, brain cell destruction correlates well with the intracerebral presence of CD8+ T cells and the expression of MHC class I antigens. Moreover, BDV-infected brain cells in vitro could be demonstrated to be lysed in a MHC class I restricted manner. These findings provide evidence that virus-infected neurons can be destructed by T cell mediated cytotoxicity which results in organ atrophy and dementia. PMID- 8219801 TI - Borna disease virus infection and affective disorders in man. AB - Borna Disease virus (BDV) can persistently infect the central nervous system of a broad spectrum of animal species. The clinical course varies from slight behavioral disturbances to a fatal neurological syndrome. In-vivo diagnosis is based on the strong humoral immune response to BDV antigens. Since also human infections could be confirmed by specific antibodies and increased seroprevalence was found in patients with chronic neurologic or immunologic disorders, the contribution of BDV or a BDV-like human variant to syndromes with yet unknown etiology became of great interest. We presented the first data of a current follow-up study on 70 psychiatric patients who were tested three times each after hospitalization. In contrast to previously found low prevalence of antibody carriers by screening (2-4%), we now found 20% positives by follow-up testing. Furthermore, of the randomly selected patients with different psychiatric diagnosis, the highest proportion of antibody carriers was detected among patients with major depression (more than 30%), compared to only 8% among patients with dysthymia (neurotic depression). This led us to hypothesize that Bornavirus infection might contribute somehow to the syndrome of major depressive illness by altering neuronal cells in the limbic system. PMID- 8219802 TI - Virus-host interactions in African swine fever: the attachment to cellular receptors. AB - Biochemical and morphological techniques have shown that African swine fever virus (ASFV) enters susceptible cells by a mechanism of receptor-mediated endocytosis. The virus binds to a specific, saturable site in the cell and this interaction is required for a productive infection. A structural ASFV protein of 12kDa (p12) has been identified to be involved in the recognition of the cellular receptor, on the basis of the specific binding of the polypeptide to sensitive Vero cells. Protein p12 is externally located in the virus particle, forming disulfide-linked dimers with an apparent molecular mass of 17kDa. The gene has been mapped within the central region of the BA71V strain genome. Sequencing analysis has shown the existence of an open reading frame encoding a polypeptide of 61 amino acids characterized by the presence of a putative transmembrane domain, and a cysteine rich region in the C-terminal part which may be responsible for the dimerization of the protein. Transcripts of the p12 gene were only synthesized during the late phase of the infectious cycle. No posttranslational modifications of the polypeptide, such as glycosylation, phosphorylation or fatty acid acylation, have been found. The comparison of the amino acid sequence of protein p12 from 11 different virus strains has revealed a high degree of conservation of the polypeptide. PMID- 8219803 TI - African swine fever virus genome content and variability. AB - A 55 kilobase pair (kb) region from the right end of the virulent African swine fever virus isolate, Malawi LIL20/1, has been sequenced. The 68 major open reading frames (ORFs) encoded are generally closely spaced and read from both DNA strands across the complete sequence. Comparison of the amino acid sequences of predicted ORFs with sequence databases identified 15 ORFs which encode proteins that are similar to proteins of known function. Two ORFs are homologous to copies of multigene family 360 (MGF360) and one ORF is homologous to copies of multigene family 110 (MGF110). Both of these multigene families have been described previously. PMID- 8219804 TI - The biology and molecular biology of scrapie-like diseases. AB - The transmissible spongiform encephalopathies (TSE's) are degenerative diseases of the central nervous system which naturally affect man (Creutzfeldt-Jakob disease [CJD], Gerstmann-Straussler syndrome [GSS], kuru), sheep and goats (scrapie), cattle (bovine spongiform encephalopathy [BSE]), mink (transmissible mink encephalopathy), mule deer, elk and antelope (chronic wasting disease). Spongiform encephalopathies have also been diagnosed in captive species of zoo antelope and in domestic cats. Much has been written about these maladies in the wake of the BSE outbreak, the tragic cases of CJD in recipients of cadaver derived human growth hormone, sex hormones or dura mater and this has stimulated a continuing public health debate about the transmissibility, prevalence and clinical variability of scrapie, CJD and related ("prion") diseases. Prions (Weissmann, Liautard, this volume) and the human (Kretzschmar, this volume) and cattle (Wilesmith, Marsh, this volume) diseases are described in more detail elsewhere. This article presents a brief overview of the biology and molecular cell biology of scrapie and rodent models of these diseases. PMID- 8219805 TI - Analysis of nucleic acids in purified scrapie prion preparations. AB - Amount, type, and size of nucleic acid molecules associated with purified prion preparations were analyzed. Return refocusing gel electrophoresis (RRGE) was developed to detect homogeneous and heterogeneous nucleic acids extracted from highly purified scrapie prion preparations. With this method all types of nucleic acids in the size range from 13 to several thousand nucleotides could be analyzed. The recovery of all nucleic acids, after deproteinization and two-phase extraction was higher than 90%. Despite extensive nuclease digestions some small polynucleotides remained. Although a scrapie-specific nucleic acid cannot be excluded, the results further define the possible characteristics for such a hypothetical molecule. If it was homogeneous in size, then it would be < 80 nt in length at a particle-to-infectivity ratio (P/I) near unity; if the other extreme, i.e. totally heterogeneous scrapie-specific nucleic acids were assumed, then scrapie-specific nucleic acids would have to include molecules smaller than 240 nt. In order to exclude the possibility that unspecific background nucleic acid is entrapped in prion-rods, infectious material has to be prepared without a proteolysis and rod formation, and the analysis of nucleic acids performed with those preparations. PMID- 8219806 TI - Epidemiology of bovine spongiform encephalopathy and related diseases. AB - The occurrence of bovine spongiform encephalopathy in Great Britain, first detected in 1986, has necessarily stimulated a large research programme. Encompassed in this are studies of the epidemiology of the disease. These commenced in 1987 and are continuing. The ensuing results have been reported and reviewed during the course of the epidemic. This paper provides a brief overview of the results of the epidemiological studies, but concentrates on the more recent features of the epidemic which are important in assessing the future course of the disease. PMID- 8219807 TI - Bovine spongiform encephalopathy: a new disease of cattle? AB - Bovine spongiform encephalopathy (BSE) was first recognized in Great Britain in 1985. Most believe that the disease is of recent origin initiated by feeding rendered animal protein from scrapie-infected sheep to cattle, then perpetuated by feeding rendered infected cattle to other cattle. This paper explores an alternative hypothesis that BSE existed in cattle populations in an unrecognized form for a much longer time until amplified by changes in the rendering process that allowed cattle to cattle transmission to occur. This viewpoint is supported by observations that transmissible mink encephalopathy, a disease that first occurred 45 years ago, is likely caused by feeding downer cows to mink, and that the sporadic form of Creutzfeldt-Jakob disease occurs spontaneously with no evidence of natural transmission. This epidemiologic scenario on the origin of BSE has important implications for prevention of the disease in BSE-free countries. Mainly, emphasis needs to put on practices of feeding animal protein to cattle rather than in reducing the prevalence of sheep scrapie. If BSE is already present in the cattle population, the major threat becomes feeding cows to cows. PMID- 8219808 TI - Human prion diseases (spongiform encephalopathies). AB - Prion diseases (spongiform encephalopathies) in humans are Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS), and kuru. Clinically, they are characterized by an inexorably progressing neurological illness with dementia and ataxia as the most prominent signs. The classical neuropathological changes are limited to the central nervous system and consist of spongiform degeneration, amyloid plaques, astrocytic gliosis, and nerve cell loss. The human spongiform encephalopathies, which for many years were considered neurodegenerative disorders of unknown etiology, were finally recognized as transmissible diseases similar to scrapie in sheep in the late 1960's. The infectious agent appears to consist of protein devoid of functional nucleic acid and has been termed prion to distinguish it from viruses. The prion hypothesis has gained wide acceptance through the finding that mutations of the prion protein gene are associated with heritable human prion disease. Different mutations appear to cause prion disease with a distinct pattern of clinical and pathological features in a great number of families. Certain mutations of the PrP gene have been shown to be associated with clinical and neuropathological changes not typical of any variant of human prion disease known to date. A new classification of prion diseases based on the molecular biology and biochemistry of the prion protein is likely to emerge. PMID- 8219809 TI - Variability of the envelope regions of HCV in European isolates and its significance for diagnostic tools. AB - Following the original description of HCV in 1989 a tremendous amount of sequence data is now available. Based on the 8 complete nucleotide sequences published so far at least 4 genotypes can be distinguished. Partial sequences of additional HCV isolates indicate the existence of further genotypes. A serological typing is not yet possible. For detection of virus, reverse transcription and amplification of the 5' non coding region is most commonly performed. This region of the genome is highly conserved among all isolates. In this study we used regions of the E1 and E2 gene in order to classify HCV isolates. The nucleotide sequences of regions in E1 and E2 gene of different European isolates from Germany, Croatia, Hungary, and Rumania were determined and compared to recently published RNA sequences of American and Japanese HCV isolates. The cDNA, obtained by reverse transcription of viral RNA extracted from sera was amplified by nested PCR, cloned and sequenced. Within 564 nucleotides (nt) of E1 we found 87-90% homology (and 89-92% homology at aa level) compared to sequences of Japanese origin and 73 74% homology (77-81% at aa level) compared to the prototype HCV sequence (ptHCV I). In all characterized isolates the sequence of E2 (643 nucleotides) showed a homology of about 83% at the nucleotide level as compared to genotype II sequences, and a homology of about 70% to genotype I. Our results confirm the existence of two hypervariable regions in the E2 gene of genotype II sequences. Our results also indicate together with other reports from European HCV isolates that genotype II is predominant in Europe. PMID- 8219810 TI - Distribution of cytopathogenic and noncytopathogenic bovine virus diarrhea virus in tissues from a calf with experimentally induced mucosal disease using antigenic and genetic markers. AB - A comparative analysis of the distribution of cytopathogenic (cp) and noncytopathogenic (ncp) bovine virus diarrhea disease (BVD) virus in tissues from a calf with experimentally induced mucosal disease was performed using immunohistology and polymerase chain reaction after reverse transcription (RT PCR) of viral RNA. For immunohistology, an antigenic marker on the superinfecting cp BVD virus defined by a monoclonal antibody (mab) was used, and overall presence of antigen was assessed with a pestivirus specific mab. The primers selected for RT-PCR detected the genomic insertion in the p125 region of the superinfecting cp BVD virus. Both methods gave consistent results. PMID- 8219811 TI - Establishment of cell lines from bovine brain. AB - As shown by immunocytochemistry, 16 cell lines of neuronal, oligodendroglial or neuronoglial origin have been established from bovine fetal brain by immortalization with SV40 virus and cloning in soft agar. The cell lines were characterized according to their cell surface markers using mono- and polyclonal antibodies. PMID- 8219812 TI - Molecular characterization of positive-strand RNA viruses: pestiviruses and the porcine reproductive and respiratory syndrome virus (PRRSV). AB - Molecular characterization has become an important tool for the analysis of viruses including their classification. The manuscript focuses on the molecular analysis of two members of the genus pestivirus (hog cholera virus, HCV and bovine viral diarrhea virus, BVDV) and of the recently discovered porcine reproductive and respiratory syndrome virus (PRRSV). The first protein encoded within the single large pestivirus ORF is a nonstructural protein with autoproteolytic activity. The cleavage site between the protease and the capsid protein p14 has been predicted previously, but recent experimental data indicate that processing occurs at a different site. The capsid protein is followed by a putative internal signal sequence and three glycoproteins which are part of the virion envelope. According to a new proposal for the nomenclature of the structural proteins of pestiviruses they are termed C, E0, E1 and E2. The genomes of BVDV pairs isolated from animals which came down with mucosal disease were analyzed. The genomes from cytopathogenic (cp) BVD viruses may contain insertions highly homologous to cellular sequences. In addition, cp BVDV may differ from its non cytopathogenic (noncp) counterpart by mere rearrangement of viral sequences. The disease PRRS, which emerged a few years ago, is caused by a single strand RNA virus; the viral genome is of positive polarity and has a size of 15 kb. Data concerning morphology, morphogenesis and virion composition suggested already that PRRSV belongs to a group of so-called arteriviruses which comprises equine arteritis virus (EAV), lactate dehydrogenase elevating virus (LDV) and simian hemorrhagic fever virus (SHFV). This conclusion has now been confirmed by analysis of genome organization, gene expression strategy and by comparison of deduced protein sequences. PMID- 8219813 TI - Serological and antigenical findings indicating pestivirus in man. AB - An epidemiological survey for pestivirus was undertaken in Zambia and Europe, in view of the recent serological findings obtained by previous studies in Europe with humans. Collected sera were tested for anti-bovine viral diarrhea virus (BVDV) specific antibodies by IIF and Western Blotting. Of those individuals tested (n = 1272), 15.3% showed a seropositive reaction to the BVDV. Anti-BVDV antibody prevalence in immuno-depressed patients (e.g. HIV positive) was investigated. A higher prevalence was revealed in HIV patients suffering from chronic diarrhoea and in those having developed AIDS Related Complex (ARC). Our of 212 persons tested for pestivirus isolation, a non cytopathic virus strain was detected in 2 buffy coat samples using IIF with a specific anti-BVDV serum. The isolation could be repeated three times during 31 days in one person. The virus was identified as a pestivirus with radioimmuno-precipitation assays and IIF-flow cytometry. A doublet of 120 kD was identified only in cell lysates, indicating a non-structural protein. In order to rule out cross reactivity 30 sera from Hepatitis C seropositive patients were tested against the isolate by IIF-flow cytometry. No antigen-specific binding could be observed. These findings indicated the occurrence of a pestivirus in man and might suggest a relationship with a pestivirus of animal origin. PMID- 8219814 TI - Molecular analysis of the human coronavirus (strain 229E) genome. AB - The nucleotide sequence of the human coronavirus strain 229E (HCV 229E) has been determined. This article describes the organization of the virus genome, the predicted viral gene products and the mechanisms which regulate viral gene expression. This information provides a basis to investigate the biology and pathogenesis of HCV. PMID- 8219815 TI - Toroviruses--members of the coronavirus superfamily? PMID- 8219816 TI - Molecular biology and evolution of filoviruses. AB - The family Filoviridae contains extremely pathogenic human viruses causing a fulminating, febrile hemorrhagic disease. Filoviruses are enveloped, filamentous particles with a nonsegmented negative-strand RNA genome showing the gene arrangement 3'-NP-VP35-VP40-GP-VP30-VP24-L-5'. Genes are flanked by highly conserved transcriptional signals and are generally separated by variable intergenic regions. They are transcribed into monocistronic polyadenylated messenger RNAs which contain relatively long 5' and 3' untranslated regions. Seven structural proteins are encoded by the genome of which four form the helical nucleocapsid (NP-VP35-VP30-L), two are membrane-associated (VP40-VP24), and one is a transmembrane glycoprotein (GP). Comparison of filovirus genomes with those of other nonsegmented negative-strand RNA viruses suggest comparable mechanisms of transcription and replication and a common evolutionary lineage for all these viruses. Sequence analyses of single genes, however, showed that filoviruses are more closely related to paramyxoviruses, particularly human respiratory syncytial virus. These data support the concept of the taxonomic order Mononegavirales for all nonsegmented negative-strand RNA viruses and the classification of Marburg virus, Ebola virus, and Reston virus in the family Filoviridae, separate from the families Paramyxoviridae and Rhabdoviridae. PMID- 8219817 TI - Coronary-prone behavior. Type A behavior revisited. AB - On the basis of prospective population studies that found a relationship between Type A behavior and cardiac morbidity and mortality independent of traditional risk factors, Type A behavior was declared a risk factor for the development of coronary heart disease. However, subsequent studies of individuals with multiple risk factors or established cardiovascular disease failed to support this association consistently. Attempts to identify toxic subcomponents of Type A behavior have supported an association between hostility and cardiac morbidity and mortality. There is evidence that Type A men are physiologically reactive in challenging situations and that behavioral programs, in combination with cardiac counseling, can reduce recurrent morbidity and mortality. PMID- 8219818 TI - Mental stress and myocardial ischemia. Correlates and potential interventions. AB - In past years, indirect evidence has suggested a link between mental stress and coronary artery disease. Recent research in coronary artery disease patients has confirmed the observation that mental stress is a potent trigger of myocardial ischemia in both the laboratory and the field. The pathophysiologic effects of mental stress appear to operate via alterations in both myocardial oxygen demand and supply. Intense negative emotion, such as hostility, and heightened cardiovascular reactivity are positively associated with this ischemia, suggesting that recognition of these factors may help identify patient subgroups at highest risk. Preliminary studies evaluating pharmacologic intervention suggest that traditional anti-ischemia therapy, such as beta-blockers and vasodilators, can reduce mental-stress-triggered ischemia in coronary artery disease patients. Behavioral and psychosocial interventions, such as reducing environmental stress through social support, altering stress perception through behavioral training, and altering the physiologic reaction to stress through physical training, also show promise as therapeutic options. Further work is needed in this fertile biobehavioral area. PMID- 8219819 TI - Brain-heart interactions. The neurocardiology of arrhythmia and sudden cardiac death. AB - Neuroanatomic connections between the brain and the heart provide links that allow cardiac arrhythmias to occur in response to brain activation. Recognition and analysis of such links in the pathogenesis of malignant cardiac arrhythmia are emphasized in this review. Neurocardiac links have been shown to produce arrhythmia both experimentally and clinically; specific examples, including stroke, epilepsy, and environmental stress are presented. We hypothesize that the individual with a diseased heart has a greater likelihood of experiencing cardiac arrhythmia and sudden cardiac death when the neurocardiac axis is activated. Reviewing possible mechanisms of brain-related arrhythmias, we suggest that the nervous system directs the events leading to cardiac damage by raising catecholamine levels and potentially inducing arrhythmia. PMID- 8219821 TI - Psychiatric complications in the critically ill cardiac patient. AB - Psychiatric consultation to the critically ill cardiac patient focuses on several common problems: anxiety, delirium, depression, personality reactions, and behavioral disturbances. A review of the causes and treatment of anxiety in the coronary care unit is followed by a discussion of delirium in the critically ill cardiac patient. A description of delirium associated with the use of the intraaortic balloon pump and its treatment with high doses of intravenous haloperidol is also included. After the initial crisis has been stabilized in the critical care unit, the premorbid personality traits of the patient may emerge as behavioral disturbances--particularly as the duration of stay increases. The use of psychiatric consultation completes the discussion. PMID- 8219820 TI - Chest pain and angiographically normal coronary arteries. Implications for treatment. AB - Approximately 20% to 30% of patients who undergo coronary arteriography for the evaluation of chest pain are found to have normal coronary arteries. These patients have a survival rate comparable to that of the normal population, yet they continue to complain of symptoms on extended follow-up, and about half of this group are disabled on account of chest pain. Once other clinically obvious disorders have been ruled out, common diagnostic considerations include microvascular angina, esophageal dysfunction, and perhaps fibromyalgia. Panic disorder, however, is the most common condition affecting these patients and can be diagnosed in at least one third of the group, with or without the presence of the other conditions mentioned. Appropriate diagnosis and treatment can reduce the psychosocial morbidity so frequently seen in these patients. PMID- 8219822 TI - Depression and its treatment in cardiac patients. AB - In general medical-surgical hospital services, depression is the most common reason for seeking psychiatric consultation in behalf of patients with cardiovascular disease. The nontreatment of depression or the use of a psychotropic agent mismatched to a patient's particular cardiac condition or individual sensitivities has considerable negative impact. Therefore, a systematic approach should be used in the differential diagnosis of depression in cardiac patients, to eliminate other psychiatric disorders and to assure the correct treatment strategy. Physicians can develop an appropriate rationale for the use of a psychopharmacologic regimen in cardiovascular settings through recognition of the diagnostic criteria for depression and through comprehensive knowledge of the pharmacologic properties and possible cardiovascular effects of these vital treatments. Standard and alternative pharmacotherapies for depression in cardiac patients are reviewed. PMID- 8219824 TI - Use of polytetrafluoroethylene surgical membrane as a pericardial substitute in the correction of congenital heart defects. AB - Patients who undergo repair of congenital heart defects have a high probability of eventually needing a repeat operation. In such cases, use of a pericardial substitute can preclude adhesion formation, thereby helping to avert the complications of a repeat sternotomy. This report describes our use of the GORE TEX polytetrafluoroethylene surgical membrane in 321 patients who underwent repair of congenital heart disease at our hospital between May of 1989 and December of 1992 (these cases account for 37.1% of all such repairs performed during this period). The patients' ages ranged from 2 days to 31 years (mean, 5.9 years). Eighty-eight patients (27.4%) had at least 1 previous median sternotomy, and 234 (73.0%) had a moderate to high probability of reoperation. Seventy-eight patients (24.3%) received a homograft, which was positioned extracardially in 63 cases. During a maximum follow-up period of 43 months (mean, 26 +/- 5.6 months), 11 patients died, for an overall mortality of 3.4%. In no case was death attributable to membrane-related complications. Postoperative complications were encountered in 12 patients (3.7%), 10 of whom required an early repeat thoracotomy. One patient had mediastinitis, for an incidence of 0.3% (in contrast to 0.2% in 864 patients who underwent similar repair without the use of a surgical membrane). No complications were encountered in the 27 patients in whom the membrane was implanted during delayed sternal closure. Seventeen patients (5.5% of the survivors) underwent a repeat sternotomy, for further correction of congenital heart defects, a mean of 20 months after the original repair. At reoperation, major complications were encountered. Although the number of reoperations was low, we conclude that use of the polytetrafluoroethylene surgical membrane for pericardial closure in children is a safe procedure that helps prevent complications at reoperation. PMID- 8219825 TI - Why referred potential heart donors aren't used. AB - Heart donor demand far exceeds supply. We evaluated donor referrals to 1 organ procurement agency in an attempt to determine why many potential cardiac donors are not used. Of 430 referrals between September 1989 and August 1991, 169 hearts (39%) were harvested. In potential donors ultimately not yielding a heart, 38.7% were unavailable because the family refused to consent to organ donation, 36% were medically unsuitable, and 16.1% did not meet standard brain death criteria. Of the 94 donors not used for medical reasons, 43.6% had cardiac arrest, 17% had hypotension, 12.8% were drug abusers, 6.4% had sepsis, 5.3% had hepatitis, 5.3% had an acute myocardial infarction, 3.2% had low ejection fraction levels, and 2.1% tested positive for human immunodeficiency virus or syphilis (4.3% were not specified). A significant difference (p = 0.001) in racial distribution surfaced; Blacks and Hispanics constituted 27.2% of the donor group but 46.3% of the non donor group. These data confirm that strategies must be created to continue educating the public and physicians in order to increase consent rates, optimize donor selection, and improve physician awareness of brain death criteria. PMID- 8219826 TI - Primary cardiac tumors. A clinical experience of 12 years. AB - From January 1980 through December 1992, we performed operations on 31 patients with primary cardiac tumors. There were 12 male and 19 female patients; the ages ranged from 7 to 71 years (mean, 47.7 +/- 18.3 years); 29 were adults and 2 were children. Twenty-six (83.9%) of the tumors were benign, and 5 were malignant. The most frequently encountered benign tumor was myxoma (22), and the most frequently encountered malignant tumor was fibrosarcoma (4). The most common symptoms at clinical presentation were those associated with cardiac insufficiency or embolization. Definition of the tumor was accomplished in all patients by echocardiography; cardiac angiography was performed in only 4 patients. All patients survived the operative procedure and were discharged from the hospital, but 4 patients with malignant disease died within 30 days. Follow-up for myxoma patients ranged from 16 to 151 months (mean, 68.5 +/- 36 months). Among the 26 patients with benign tumors, there was 1 death, 72 months after the surgical procedure, of right-heart failure due to recurrence of the myxoma. PMID- 8219823 TI - Standard and alternative adjunctive treatments in cardiac rehabilitation. AB - Cardiovascular rehabilitation is the process of restoring functional abilities degraded by a serious cardiovascular event or by a surgical procedure to preempt such an event. Cardiovascular rehabilitation also includes attempts to reverse risk factors that have contributed initially to the disease process. Rehabilitation programs generally comprise disease-related educational components, supervised prescriptive physical exercise, diet counseling and modification, cessation of tobacco use, psychoeducational interventions aimed at adjustment and coping, and relaxation and stress management to lower nonexertion related sympathetic drive. The presence of so-called coronary-prone behavior patterns can be detected, and special behavioral modifications may be indicated to mitigate these putative risk factors. This paper reviews the roles of these behavioral adjuncts in treating cardiovascular disease and its aftermath, and notes new and unusual approaches to these components of treatment, such as alternative exercises, biofeedback, yoga, and other relaxation methods. Barriers to compliance are acknowledged, and enhancement of compliance is discussed briefly. PMID- 8219827 TI - Surgical management of intracardiac myxomas. A 16-year experience. AB - Twenty-six patients with an intracardiac myxoma underwent surgical resection at our institution from 1977 through 1992. Left atrial myxoma was diagnosed in 22 patients, left ventricular in 1, right atrial in 2, and right ventricular in 1. Six patients were asymptomatic; preoperative symptoms included dyspnea, arrhythmias, embolic episodes, and syncope. The diagnosis was established with transthoracic echocardiography in all cases but one. Surgery was performed in all cases with the aid of cardiopulmonary bypass with moderate hypothermia and cold crystalloid cardioplegia. One patient with a left ventricular myxoma died in a comatose state during the immediate postoperative period. Long-term clinical and echocardiographic evaluation was performed in 19 patients; results were excellent (all the patients were in New York Heart Association functional class I or II), and no recurrences were documented. The clinical characteristics, diagnostic methods, and surgical approach are presented and discussed. PMID- 8219828 TI - A new device for evacuating air from the cardiac chambers. AB - A new device has been developed to provide complete de-airing of the heart after cardiopulmonary bypass. The apparatus consists of a special aspiration needle threaded to the bottom of a transparent bulb. A 1-way flutter valve is mounted at the top of the bulb, which creates a vacuum when the bulb is squeezed. This device has been used in 4 adults and 2 children, for both congenital and acquired heart disease. Preliminary results have shown that this device's active suctioning of air results in effective removal of air from the cardiac chambers; the transparent bulb enables the surgeon to visually determine that the de-airing procedure is complete. PMID- 8219829 TI - Pulmonary banding complicated by low origin of right pulmonary artery. AB - In our attempt to band the main pulmonary artery above the valve in a 4-month-old prematurely born infant, we erroneously banded only the left pulmonary artery, owing to the unusually low origin of the right pulmonary artery (which arose partially in the sinus of Valsalva). When severe cardiac failure recurred, the anomaly was noted upon reoperation and the band was repositioned at the level of the pulmonary valve. Since this revision, the postoperative course has been good. Low origin of the right pulmonary artery is normal in premature infants. However, origin of the right pulmonary artery from the sinus of Valsalva is a sufficiently extreme variant to constitute a surgically important anomaly. Our postmortem studies of the pulmonary arteries of 25 premature infants born without cardiac malformation showed that while the right pulmonary artery was lower than the left, it never originated from the sinus of Valsalva. This anomalous configuration of the pulmonary arteries has, to our knowledge, never been found in an infant as old as 4 months; yet we believe it should be taken into account when banding pulmonary arteries in infants. PMID- 8219830 TI - Repair of atrial septal defect due to penetrating trauma. AB - We report a case of stab wound to the heart resulting in an atrial septal defect and perforation of the anterior leaflet of the mitral valve, which we repaired successfully 7 years after the injury. To our knowledge, repair of an atrial septal defect due to penetrating trauma has never before been reported. Investigation of possible valvular heart disease in a patient with a history of chest trauma should be aimed at identifying both intracardiac shunts and valvular abnormalities, so that a complete repair can be performed. PMID- 8219831 TI - Screening for colorectal cancer. Scoop, 'scope, or skip? PMID- 8219832 TI - Are you a maximalist, a minimalist, or a ritualist? PMID- 8219833 TI - Physicians and drug companies interact. PMID- 8219834 TI - Radiology rounds. Porcelain gallbladder (with cholelithiasis). PMID- 8219835 TI - Case definition revised. Surveillance case definition for AIDS in Canada. Laboratory Centre for Disease Control. PMID- 8219836 TI - A causal relation has been demonstrated between diphtheria-tetanus-pertussis vaccine and which of the following conditions? PMID- 8219837 TI - Can you identify this condition? Dermatomyositis. PMID- 8219838 TI - Family practice clinics. Survey of family practice residents' attitudes. AB - All residents of McGill University's Department of Family Medicine were surveyed by mail about their family practice clinic experience. Residents were generally satisfied with their training site and their supervision, but noted problems with volume and diversity of patients, learning certain procedures, and knowledge of community resources. They did not want more family medicine clinic time. PMID- 8219839 TI - Adverse events temporally associated with immunizing agents. AB - In Canada during 1990, a total of 2832 reports of adverse events temporally associated with the administration of immunizing agents were received by the Childhood Immunization Division of the Laboratory Centre for Disease Control. This paper summarizes the data collected, describes the surveillance system, and demonstrates that, with more than 12,000,000 doses of vaccines distributed during 1990, the incidence of adverse events reported is very low. PMID- 8219840 TI - Faculty development in family medicine. A reassessment. AB - The 16 Canadian departments of family medicine were surveyed to ascertain the availability and content of faculty development activities. The results suggest numerous changes since 1985 and a strong commitment to faculty development. With the consolidation of many faculty development activities to date, departments should now consider other methods of faculty development, broaden their activities beyond the current emphasis on "teaching skills," examine the possibility of integrating faculty development with faculty evaluation, and conduct more systematic program evaluations. PMID- 8219841 TI - Flexible fibreoptic sigmoidoscopy. Safe and effective for family practice. AB - Flexible fibreoptic sigmoidoscopy can detect malignancy, polyps, and other common diseases of the large bowel when they are distal to the splenic flexure. The procedure is safe and not painful when correctly performed. Family physicians could play an important role in the earlier diagnosis and prevention of colorectal cancer by adding the procedure to their repertoire. PMID- 8219842 TI - Hypertension and the J-curve. How low should you go? AB - Recent analyses of treated blood pressure versus events suggest that drug treatment might result in an increase in coronary events or mortality at treated diastolic pressures below 80 mm Hg (the "J-curve"). However, this contention is highly controversial. Both sides of the argument are examined and a balanced approach for target blood pressure goals on treatment is outlined. PMID- 8219843 TI - Doing obstetrics and staying alive. AB - Many family physicians have a love-hate relationship with childbirth care and struggle to balance their personal and family needs with the need to provide high quality personal care during labour and birth. Many false assumptions undermine family practice obstetrics. Strategies are presented to simplify obstetric care for women and families while promoting reasoned self-care for physicians. PMID- 8219844 TI - Rural psychiatric services. A collaborative model. AB - Psychiatric services are difficult to obtain in rural communities because few psychiatrists practise outside urban centres. Family physicians who are willing to develop their skills with the support of their psychiatrist colleagues could alleviate this problem. This article describes a community mental health clinic where a family physician acts as psychiatric consultant. PMID- 8219845 TI - Glue-sniffing neuropathies. AB - The commonly used term for solvent abuse, glue sniffing, generally encompasses a variety of substances, including spray paint, thinners, nail varnish remover, gasoline, marking pens, and lighter fluids. Inhaled vapours eventually reach the lipids in the nervous system, where they can be stored for long periods. In three cases of glue-sniffing-related neurotoxicity, the peripheral nervous system was affected in two cases and predominantly the central nervous system in the third. Unfortunately follow up is difficult with this patient population and symptoms are often complicated by alcohol abuse. PMID- 8219846 TI - Substance abuse in later life. AB - Substance abuse affects an appreciable portion of the elderly population. Elderly people have characteristics that could hinder identification, diagnosis, intervention, and treatment of substance abuse. If physicians use strategies specific to the elderly, management is often successful. PMID- 8219847 TI - Subclinical hypothyroidism. To treat or not to treat. AB - The term subclinical hypothyroidism has been used to describe the syndrome of high serum levels of thyroid-stimulating hormone associated with normal levels of thyroid hormone. Diagnosis requires a sensitive method of measuring TSH. Because the syndrome does not invariably lead to overt hypothyroidism, it would not be appropriate to institute lifelong levothyroxine therapy in every case. Cases that do not qualify for immediate therapy need close follow up. PMID- 8219848 TI - [Physician patient relationship apprenticeship. Direct supervision of II residents in a family medicine unit]. PMID- 8219849 TI - Infant feeding through the ages. PMID- 8219850 TI - Clinicians and researchers. A clash of cultures? PMID- 8219851 TI - Mixing politics and medicine. PMID- 8219852 TI - Cutting our throats? PMID- 8219853 TI - Do's and don'ts when examining children. PMID- 8219854 TI - Selecting a competent chiropractor. PMID- 8219855 TI - To crack or not to crack. PMID- 8219856 TI - Your patient's health and environmental pollution. Toxic chemicals in sport fish and wildlife. PMID- 8219857 TI - Radiology rounds. Intrauterine contraceptive device. PMID- 8219858 TI - Dermacase. Myxoid cyst. PMID- 8219859 TI - Using pyridoxine to treat carpal tunnel syndrome. Randomized control trial. AB - In this study, we examined prospectively the effect of pyridoxine on idiopathic carpal tunnel syndrome. Thirty-two patients with the disease were randomized to receive treatment or placebo. No differences in outcome were found in electrophysiologic signs, clinical signs, or significant symptoms. Our findings do not support the use of pyridoxine for treating carpal tunnel syndrome. PMID- 8219860 TI - Oral and intravenous rehydration of children. AB - We compared oral rehydration therapy (ORT) with rapid intravenous rehydration (IV) in 42 young children with mild to moderate dehydration due to diarrhea. Overall, treatment was successful for 82% of the ORT patients and for 78% of the IV patients. Many physicians in hospitals are unfamiliar with the use of ORT for treating dehydration. PMID- 8219862 TI - Hormone replacement therapy. Risks, benefits, and costs. AB - Epidemiologic evidence on the risks and benefits of hormone replacement therapy (HRT) for postmenopausal women is accumulating. The apparent 50% reduction in risk of cardiovascular mortality could lead to universal HRT. Until a prospective, controlled trial is concluded, women must consider all the consequences of HRT. For the undecided, who would take HRT only to prevent osteoporosis, bone mass estimates might be warranted. PMID- 8219861 TI - Diarrhea-associated hemolytic uremic syndrome. AB - Diarrhea-associated hemolytic uremic syndrome (D+ HUS) is the most common cause of acute renal failure in children. The authors report their experience with D+ HUS with 114 patients assessed in Calgary from 1980 to 1992. Epidemiologic, clinical, and pathologic aspects are discussed. PMID- 8219863 TI - Acute otitis media in children. Role of antibiotic therapy. AB - In a review and critical appraisal of the literature on antibiotic therapy for acute otitis media in children between 1939 and 1991, poor evidence supported the routine use of antibiotic therapy. Good evidence supported initial symptomatic treatment and institution of antibiotic therapy only in cases of an irregular course (fever or pain for more than 48 to 72 hours) in children 2 years and older. This approach cannot be recommended for children 2 years and younger because this age group has been excluded from most studies. PMID- 8219864 TI - Family physicians and the health care team. AB - Today, family medicine deals with a spectrum of physical, social, psychological, and developmental issues in day-to-day practice. It is unrealistic to expect family physicians to intervene with all issues. Multidisciplinary health care teams can provide comprehensive and effective care, but teamwork does not occur automatically. This article reviews the process required to develop an effective team and the role of family physicians on health care teams. PMID- 8219865 TI - Caring for patients with HIV infection. Management plan for family physicians. AB - Caring for and treating patients living with human immunodeficiency virus is challenging for busy family physicians. I present one strategy for managing patients with this complex infectious disease. Using averaged T4 blood cell counts as a marker of disease progression, I use antiretroviral treatment and preventive drug therapy against the complications of HIV infection. PMID- 8219866 TI - Adjuvant chemotherapy in stage I breast cancer. More harm than benefit. AB - Clinical trials of adjuvant chemotherapy for breast cancer have shown a prolonged disease-free interval but no improvement in survival. This review of the evidence indicates that adjuvant therapy induces an antineoplastic drug resistance that makes "salvage" therapy less effective. The benefit that is seen only in group statistics, not in an individual, must be weighed against the harm an individual incurs from the chemotherapy. PMID- 8219867 TI - Anxiety disorders. Part 1: Diagnosis and treatment. AB - Anxiety disorders often take second priority in clinical practice because many physicians do not understand them or their treatment. This paper reviews the diagnostic groupings of anxiety disorders according to the American Psychiatric Association's Revised Diagnostic and Statistical Manual of Mental Disorders (DSM 3-R) and discusses differential diagnosis and treatment. PMID- 8219869 TI - The history of the stethoscope. PMID- 8219868 TI - Common colds. Causes, potential cures, and treatment. AB - Colds are a common clinical condition, caused by a variety of pathogens. This article reviews the etiology of the cold, proposed cures, symptomatic relief, method of transmission, and advice for patients. Transmission through indirect contact, or self-inoculation, seems more common than was once thought. Experimental antiviral agents hold some promise; in the meantime, symptomatic relief is available. PMID- 8219870 TI - Continuing medical education revisited. PMID- 8219871 TI - Waiting for the other shoe to drop. PMID- 8219872 TI - Key factors in the implementation of a clinical quality improvement project: successes and challenges. PMID- 8219873 TI - Perceptions of VA chiefs of staff on total quality management implementation. AB - A national survey of United States Veterans Affairs (VA) Medical Centers (n = 167) chiefs of staff was conducted. The survey solicited feedback of the attitudes and perceptions of respondents toward planning, implementation, and monitoring of the Total Quality Management (TQM) process in their facilities. A Likert scale type of responses were collected and analyzed to measure the degree of agreement or disagreement of the respondents to survey statements on TQM. The survey included responses to three sections of the questionnaire: 25 statements on TQM, information on the TQM process status in the facility, and demographics of respondents and their facilities. The results of the survey indicate a considerable involvement of responding chiefs of staff in the TQM process and indicated their willingness to support it. Respondents agreed that TQM requires time and commitment of top management, and, again, they indicated their willingness to devote the time necessary for the process to succeed. They were, however, cautious in endorsing the statement that TQM will decrease health care costs (fiscal and human). The survey provides information that should prove valuable to administration in planning TQM and Continuous Quality Improvement efforts. PMID- 8219874 TI - Enhanced length of stay management through monitoring of discharge planning parameters. AB - Traditional data collection in discharge planning programs has been largely retrospective, measuring the patient's length of stay and unnecessary hospital days at the point of discharge. Although the data collection is useful, it does not lend itself to corrective actions on a concurrent basis. Carney Hospital has developed a data base that monitors patient status daily in order to identify when a length of stay problem is developing and when corrective actions are succeeding. The Patient Tracking System is an interactive computer report utilized by Continuing Care staff, Utilization Review staff, and clinical managers on the patient care units. It is a caseload register that operates from the admission transfer discharge (A/T/D) system of the hospital and sorts inpatients by discharge planning status, length of stay, discharge planning worker, and nursing unit. It is the basis for a weekly management review that identifies numbers of patients and average length of stay to date of key groups of patients proven to impact the overall length of stay in the hospital. Carney Hospital has successfully utilized this system to alert managers to any length of stay "creep," to identify the sources of the length-of-stay problem, and to mobilize key personnel to take corrective actions. The system is easy to use and is an effective length-of-stay management tool. PMID- 8219875 TI - Corporate culture in a mythless society. PMID- 8219876 TI - Translating research into practice: the implementation of an in-home crisis intervention triage and treatment service in the private sector. AB - This report focuses on the implementation and evaluation of a 24-hour-a-day, in home crisis intervention, triage, and treatment service in a 110,000 member health maintenance organization. The in-home crisis intervention service averted the need for hospitalization in 80% of referred patients presenting for inpatient admission. A two-year analysis, involving more than 600 patients, found nearly four times fewer severe psychiatric relapses requiring readmission among patients triaged by the crisis intervention service, compared to patients hospitalized without going through its service. The service saved approximately 3,347 days of hospital-based psychiatric care over the two-year study period. This program evaluation data, combined with previous research, documents that for the vast majority of hospitalized psychiatric patients, intensive in-home crisis intervention and treatment services are a more effective and cost-efficient form of care. PMID- 8219877 TI - How much routine preoperative laboratory testing is enough? AB - Routine preoperative laboratory testing has become dogma to many. Often, surgeons, anesthesiologists, hospital administrators, and even patients expect that there will be some "labs" on the chart prior to any operative procedure. Many have questioned the usefulness and cost-effectiveness of such a policy. There is little evidence to support the need for routine preoperative testing and much evidence against it. Preoperative testing should be based on appropriate indications. This makes the assessment of the preoperative laboratory evaluation difficult for a medical quality assurance program. The question that arises is, how much routine preoperative laboratory testing is enough? The answer to this question depends on (a) the purpose of this testing and (b) the limitations and potential misinterpretations of laboratory testing. This article will discuss the reasons for the potential misinterpretation of laboratory tests and then the data supporting selective preoperative laboratory testing. PMID- 8219878 TI - Quality assurance in the department of pediatrics. An application of quality management. AB - A continuous quality improvement program can provide the means through which medical organizations can guide their activities. This article illustrates how a pediatrics department in an urban medical center incorporated continuous quality improvement into the management of health services. Key elements of the Quality Assurance program included the organization and facilities in the department of pediatrics, important processes related to patient care, and outcome measures. If a structure is established that allows participation in decision-making and mutual adjustment, trained professionals can perform up to their standards and those standards of their peers. Involvement of physicians in the design of quality management programs and other administrative strategies offer an opportunity to develop a working formula for ongoing success. PMID- 8219879 TI - Total quality management and quality assurance: discussing the differences. AB - Total Quality Management and Continuous Quality Improvement have become the "buzz" phrase for the 1990s. Everyone seems to be jumping on the band wagon. But what is it, and is it right for your organization? We believe that Total Quality Management is superior to many Quality Assurance programs currently in use. There are, however, many considerations to take into account before implementing a Total Quality Management program. The purpose of this article is to explain the pros and cons of Total Quality Management and standard Quality Assurance programs and to compare and contrast these two approaches. This article focuses on barriers to successful implementation and presents several questions organizations can utilize in assessing readiness for a quality management program. PMID- 8219880 TI - Interview with Chelissa Brown. Interview by Ina May Gaskin. PMID- 8219881 TI - The case for childhood immunization. PMID- 8219882 TI - Doing adoption right: at Summertown's Farm community, they had a better way when it came to caring for children. PMID- 8219883 TI - I have been meeting a lot of aspiring midwives lately. PMID- 8219884 TI - Why an obstetrician couple chose an "alternative" birth. PMID- 8219885 TI - Canadian health system. PMID- 8219886 TI - Midwives as national health care. PMID- 8219887 TI - The different styles midwives have. PMID- 8219888 TI - Up dated statistics. PMID- 8219889 TI - Kayla Rose. PMID- 8219890 TI - Some babies die. PMID- 8219891 TI - Interview with Nonkululeko Tyehemba. Interview by Ina May Gaskin. PMID- 8219892 TI - Occupational exposure standards. Historical outline and present state. AB - The paper presents the history of hygienic standards setting in various countries, as well as the current situation in this respect. Methodological approaches to hygienic standards setting in the USA and USSR have been analysed and compared. The paper shows also the contribution of international organizations to unification of both the definition and the approach to MAC setting. The authors present systems of MAC setting in such countries as USA (ACGIH, NIOSH, OSHA), former USSR, Germany, Scandinavian countries, Hungary and Poland. The paper comprises also classification of substances and carcinogenic agents adopted by IARC as well as the classifications in those countries which publish lists of carcinogens. PMID- 8219893 TI - Occupational medicine in east European journals of 1992; Part 1. PMID- 8219894 TI - Experimental study of subacute oral, dermal and inhalation toxicity of bulmoscide preparation. AB - The purpose of this study is to give the toxicological characteristics of subacute oral, dermal and inhalation exposure of microbial preparation Bulmoscide, which is based on bacterium Bacillus thuringiensis, serotype H-14. The study was performed on sexually mature Wistar rats of both sexes. No significant changes in non-specific, clinico-laboratory and biochemical parameters as well as morphological examinations in any tested groups compared to the control groups were revealed. The doses 110 mg.kg-1 (1.32 x 10(9) sp.kg-1) at oral administration in duration of 90 days, 3000 mg.kg-1 (3.6 x 10(10) sp.kg-1) in 21 day dermal application and maximum attainable concentration of dust aerosol 18 mg.kg-3 (2.2 x 10(8) sp.m-3) during a 30 day inhalation exposure are "no toxic effect" levels. On the basis of the data, the selective bacterial insecticide Bulmoscide has been determined to be of low toxic and low hazardous preparation in compliance with the Hygiene Classification of pesticides. PMID- 8219895 TI - Study on carcinogenicity of clinoptilolite type zeolite in Wistar rats. AB - The long term carcinogenicity of clinoptilolite was examined in Wistar rats. Respirable clinoptilolite was given intratracheally in doses 0, 30, or 60 mg/animal to groups of 60 or 50 male and 50 female rats on one occasion. No significant dose-related increase was found in the incidence of tumours in any organ or tissue. The results indicated that clinoptilolite type zeolite had no carcinogenic activity in Wistar rats. PMID- 8219896 TI - Effects of acute combined exposure to N-butyl alcohol and M-xylene. AB - The effects of combined exposure to m-xylene and n-butyl alcohol on rotarod performance and motor activity in rats and respiratory rate in mice were investigated in the condition of an acute inhalation experiment. Rotarod performance and motor activity were tested in rats exposed to various concentrations of m-xylene, n-butyl alcohol and their mixture consisting of 50 Vol-% m-xylene and 50 Vol-% n-butyl alcohol immediately after termination of a 4 hour exposure period. The respiratory rate in mice was recorded in short 6 min duration exposures to individual solvents and their 50:50 Vol-% mixture. Both solvents and mixtures caused concentration-dependent disturbances of rotarod performance in rats. The medial effective concentration (EC50) for the effect amounted 6530 ppm, 1980 ppm and 3080 ppm for n-butyl alcohol, m-xylene and their mixture, respectively. Both solvents and their mixture changed the spontaneous motor activity in the rat. Because of a two-phase effect, the concentration dependence of the observed changes could not be defined. The evaluation of the combined effect in motor activity test was carried out by comparing experimental values with expected ones assuming the summation of individual solvent effects. The tested solvents resulted in a concentration-dependent decrease in respiratory rate in mice. The concentration which decreased the respiratory rate to 50% (RD50) was 3010 ppm, 1360 ppm and 3140 ppm for n-butyl alcohol, m-xylene and their mixture, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8219897 TI - Age associated differences in effects of benzene on mixed-function oxidases in phenobarbital-treated rats. AB - These studies were performed on 5, 10, 30, 60 and 540 days old female Wistar rats. The animals were treated i.p. with phenobarbital (50 mg/kg body weight) and benzene (250 mg/kg body weight). In smooth (SER) and rough (RER) hepatic microsomes, the mixed function oxidases activity were studied. The earlier phenobarbital induction decreased the negative benzene influence. In all examined animals this was observed for protein, cytochrome P-450, and demethylase 4 aminopyrine activities. A partial decrease of inhibition was noticed only for activities of NADPH-cytochrome bs and NADH-cytochrome bs reductase activities, phenobarbital did not significantly change the effect of benzene. PMID- 8219898 TI - Experimental carcinogenicity and mutagenicity of non-asbestos natural fibres- preliminary report. AB - The aim of this investigation was to quantify the carcinogenic and mutagenic activity of antigorite occurring in the form of admixtures in different mineral raw materials (serpentinite, magnesite, dolomite and nickel ore). The carcinogenicity of dusts was evaluated after intraperitoneal injections of 5 mg (mice) or 20 mg (rats) of dust suspended in saline. A pathomorphological examination was performed in all the dead animals. For two raw materials- serpentinite and nickel ore--their mutagenic potency was investigated (SCE test was used in this study). Results obtained in the experiments on animals (rats and mice) showed that the biological aggressiveness of the mineral raw materials tested was associated with the content of antigorite fibres. Particularly the frequency of mesothelioma (5-85%) was related to the number of antigorite fibres longer than 5 microns. Both of the investigated raw materials (serpentinite and nickel ore) were mutagenic in the SCE test. PMID- 8219899 TI - Mutagenic activity of drinking water in Wroclaw, Poland. AB - The Salmonella mutagenicity test was applied to the evaluation of mutagenic activity of Wroclaw drinking water. Contaminants of water samples were concentrated by adsorption on XAD-2 resin. After while they were eluted sequentially with acetone, dichloromethane/methanol (1:1, v/v) and methanol, and then obtained organic extracts were evaporated to dryness. The extracts were then dissolved in DMSO and examined by using the Ames test. The results proved significant contamination of drinking water with mutagenic substances. Hydroxyapatite column chromatography performed after direct incubation of standard DNA probes with tested water extracts showed that drinking water was contaminated with DNA interstrand cross-linking substances. Filtration of tap water through carbon filters markedly reduced mutagenic activity of tested water extracts, whereas ceramic filters were more efficient in depleting of DNA interstrand cross-linking contaminants. PMID- 8219900 TI - Health risk assessment in children exposed to lead compounds in the vicinity of mine-smelter plant "Orzel Bialy". AB - Investigations of environmental exposure to lead were performed in 1028 children from a very polluted industrial region affected by emissions from the lead mine and smelter plant "Orzel Bialy". A group of 629 children was used as the reference population from non-polluted parts of Poland. The lead blood concentrations in exposed groups of children were considerably higher than in the reference group and 26% of younger children and 11% of older children exceeded the safe limit value of 20 micrograms/dl. Children with the highest health risk in which Pb-B amounted to 40-50 micrograms/dl (4.2% of exposed children) were recommended for immediate medical examination. As preventive measures, improvement of hygienic life conditions and frequent trips of exposed children to non-polluted areas, were recommended which should decrease the internal lead dose. PMID- 8219901 TI - Occupational medicine in Polish journals of 1992; Part 1. PMID- 8219902 TI - Current principles of hygienic standards setting. Part I. AB - A critical analysis of the present situation with respect to hygienic standard setting is presented. The authors introduce requirements for developing scientifically based exposure limits for chemicals as well as differences between documentation of recommended exposure limits for the agents occurring in the working environment and in the communal environmental medicine. PMID- 8219903 TI - Development of the aggregation model of adverse environmental and health effects for evaluation of large areas of ecological hazard. AB - The model of aggregation of 12 parameters describing the environmental and health effects in areas of ecological hazard has been elaborated. The values of particular indices create the characteristic profile useful for selection of dominant environmental problems. The general index of hazard is suitable for establishing priorities among ecological hazard areas. PMID- 8219904 TI - Cadmium, zinc, and copper levels in the kidneys and liver of the inhabitants of north-eastern Poland. AB - Concentrations of Cd, Zn, and Cu were determined in the renal cortex and the liver of 79 persons who died in 1991 in Bialystok and its vicinity. The mean concentrations were: 30.5 +/- 27.7 micrograms Cd/g, 37.6 +/- 18.5 micrograms Zn/g, 2.6 +/- 2.5 micrograms Cu/g, and 2.1 +/- 2.2 micrograms Cd/g, 52.4 +/- 20.5 micrograms Zn/g, 4.0 +/- 2.1 micrograms Cu/g, respectively, in the renal cortex and the liver, at the mean age of 51.1 +/- 19.1 years. Smokers showed almost twice higher Cd levels in the cortex than non-smokers. The mean whole body retention calculated for cadmium was 18.9 +/- 15.9 mg. Smoking increases it by about 60%--from 13.7 mg in non-smokers to 22.8 mg in smokers. In the inhabitants of the investigated region cadmium levels (kidney, liver, whole body retention) were lower than in persons from Lodz and Katowice regions. PMID- 8219905 TI - The influence of cigarette smoking on sister chromatid exchange frequencies in peripheral lymphocytes among nurses handling cytostatic drugs. AB - Genotoxic compounds and various cancer chemotherapeutic agents can interact with tobacco smoke synergistically, especially among cigarette smoking nurses handling cytostatic drugs. The aim of the study was to examine the hypothesis that tobacco smoking has a greater influence on sister chromatid exchange (SCE) frequencies among nurses than the influence of cytostatics in working conditions. The frequencies of SCE in lymphocytes investigated among hospital staff who handle anti-cancer drugs were higher than in a control group which did not handle them (smokers and non-smokers). The increase of SCE frequencies was observed more often among cigarette smoking nurses and less among non-smoking nurses who handle cytostatics 3 times a week. PMID- 8219906 TI - Biological markers of early health effects in the assessment of the risk of cancer in people exposed to environmental carcinogens. AB - Biomarkers of early health effects represent the intermediate stages of the carcinogenesis process, between the initiation and conversion stage and the clinically overt neoplastic disease. The cellular processes indicated by those markers correspond, therefore, to the promotion process. Detection of those cellular processes is extremely important, as the promotion process lasts for many years and bears some signs of being reversible. The promotion process, consisting of a range of consecutive cellular changes involves, among others, activation of proto-oncogens and their transformation into oncogens, and inactivation of the suppressor genes. Therefore, the possibility of observing the trends of those changes by monitoring protein products of the oncogens and suppressor genes in the easily available material (blood, urine) is very useful. Inhibition of intercellular communication seems to play an extremely important role in the complex mechanism of transformation of a normal cell into a neoplastic one. During the carcinogenic process promotion stage, the inhibition is associated with the proteins which form the intercellular junctions and participate in cellular adhesion. That group of proteins includes carcinoembryonal antigen (CEA) and tissue polypeptide antigen (TPA), the tumour antigens which have been known for years. The possible relationship between increased TPA and CEA concentrations is supported not only by the data from the oncology but also by the data from the studies on populations exposed to agents known to increase the risk of neoplastic disease. PMID- 8219907 TI - Metabolic disposal of antipyrine and lipid peroxidation indices in volunteers jointly exposed to industrial organic solvents and ethanol. AB - Each of twelve volunteers, at 2 week intervals, received 1 g of antipyrine, a test drug, and were exposed for 4 h either to toluene (375 mg/m3) or xylene (435 mg/m3) singly or in combination with ethanol (0.45 g/kg body wt. before the onset of exposure and 0.15 g/kg thrice every 1 h during exposure to maintain a steady level of ethanol in blood approximately 11 mmol/dm3). No significant differences were found in salivary antipyrine half-life (T1/2 approximately 12 h); and clearance (ClAP approximately 0.83 cm3/s) between control and groups exposed to solvents and/or ethanol. Nevertheless, a tendency to increase the metabolic rate of antipyrine in xylene-exposed group (T1/2 approximately 6.8 h; ClAP approximately 1.40 cm3/s) and counteraction of ethanol (T1/2 approximately 15 h; ClAP approximately 0.63 cm3/s) should be noted. The stimulation of lipid peroxidation in the serum as a biological effect of combined exposure to ethanol and toluene/xylene was observed. PMID- 8219908 TI - Experimental toxic liver damage and hepatic plasma clearance of 99mTc-mebrofenin (iminodiacetate derivative). I. Early, acute CCl4-induced liver damage in rabbits. AB - Liver damage was induced in rabbits by graded doses of carbon tetrachloride. The damage was assessed by means of quantitative morphometry using necrosis and steatosis of the parenchyma as end points. Biological response was measured utilizing a series of typical biochemical indices of liver damage as well as plasma clearance by the liver 99mTc-mebrofenin (an IDA derivative) and quantified indices of uptake and organ transfer of the compound. No correlation was found between the CCl4 dose and its effect (i.e. degree of necrosis and steatosis of liver). However, a very strong negative correlation was found between the degree of necrosis in individual animals and value of the clearance. The extent of the damage was positively correlated with liver transfer rate of 99mTc-MBF. Plasma activity of ALAT, TG, GGTP and AspAT were higher in the poisoned animals, however, only increments of activity of GGTP, ALAT and LDH showed statistically significant correlation with the individually assessed damage (necrosis). PMID- 8219909 TI - The disposition and metabolism of methyl acrylate in male Wistar albino rats. AB - The present study was designed to investigate methyl-[2,3-14C]acrylate (MA) distribution, excretion, and metabolism. Data presented here show that the radioactivity derived from MA is rapidly absorbed after i.p. and p.o. administration and distributed into all major tissues of rats. The highest concentration of MA-derived radioactivity was detected mainly in the liver and kidneys at 1 (i.p.) or 2 (p.o.) hours after dosing. There were only slight differences observed in the dynamics of tissue distribution and excretion in relation to the route of administration. The major route of MA excretion was CO2 exhalation (approximately 54% of the administered dose in 48 h) followed by urinary excretion. Two metabolites were identified in the urine, namely, N-acetyl S-(2-methylcarboxyethyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine, and ratio between those was about 1:1. PMID- 8219910 TI - International Symposium: Work-Related Diseases--Prevention and Health Promotion (27-30 October, 1992, Linz, Austria. PMID- 8219911 TI - Bibliographic review. Occupational medicine in Polish journals of 1992: part 2. PMID- 8219912 TI - Bibliographic review. Occupational medicine in East European journals of 1992: part 2. PMID- 8219913 TI - International Code of Ethics for occupational health professionals. PMID- 8219914 TI - Insulin antibody assay: a statistical evaluation of sensitivity, precision and reproducibility in healthy subjects. AB - Eighty-seven sera from healthy non-diabetic subjects, negative for islet cell antibodies, were analysed for 125I-insulin serum binding capacity by a commercial radioimmunoassay. In order to define the detection limit of the assay for insulin antibodies we used the corrected binding capacity to 125I-insulin of the normal sera obtained by competitive inhibition with excess of unlabelled insulin. To test the reproducibility of the results as a function of the tracer decay the sera were re-examined after intervals of 17 and 37 days, when a drift of more than 1% was found in the period investigated. Using the corrected bindings improved reproducibility considerably. The extra variation between the three assays, taking into account the decay of the tracer, was negligible. The main component of error contributing to these variations among individuals was found to be the precision, defined as the mean standard deviation among the replicates, which is SD(c) = 0.325%. We conclude that this assay is suitable for the screening of positive insulin autoantibodies in pre-diabetic subjects, and recommend that the estimate of precision from the replicates with excess insulin be used and that the detection limit be set at three times the estimated SD(c). PMID- 8219915 TI - Activated partial thromboplastin time reagents: an evaluation. AB - Nine automated, activated partial thromboplastin time (APTT) reagents were evaluated on an automated coagulometer, in comparison with a manual reagent. The study consisted of three separate stages: 1) to choose a reagent that had a working stability between 4 degrees C and 8 degrees C for seven days and heparin sensitivity between 0 and 0.8 iu/ml; ii) assessment of sensitivity to specific factor deficiencies, particularly factors VIII, IX, XI and XII using standardised plasma serially diluted with factor-deficient plasma; and iii) assessment of sensitivity to the presence of a lupus anticoagulant, from a known positive panel. Only one reagent fulfilled all the essential criteria as an acceptable replacement for the manual reagent. PMID- 8219916 TI - Lupus anticoagulant testing: effect of the platelet count on the activated partial thromboplastin time. AB - The activated partial thromboplastin time (APTT) is often used as a test to diagnose patients with lupus anticoagulants. It is recommended that platelet-poor plasma be used in the APTT test. In this study the effects of residual platelet contamination on lupus anticoagulant and antiphospholipid antibody testing are described. In fresh samples the residual platelet contamination has no significant effect whereas in frozen samples the effect of residual platelet contamination can have a significant effect on the APTT testing. PMID- 8219917 TI - Development of a MUMPS-based anticoagulant management system. AB - A computerised anticoagulant management system written in Digital Standard MUMPS, and incorporated into an ACT Medisys Computer Integrated Laboratory Management System (CILMS), has been developed. The system will automatically adjust and prescribe warfarin dosage for selected patients and set clinic appointments based upon defined criteria. Other significant features include printed patient dosage cards, cumulative worksheets for clinicians, clinic and transport lists, statistical searches, rapid enquiry facilities and operator alerts. After 20 months of successful running, a system has evolved which has greatly improved the efficiency of the anticoagulant clinic and the quality of anticoagulant control. Significant savings have been made in medical staff time, patient waiting times have been greatly reduced and the stability of warfarin control has increased. The service has more recently been extended to patients controlled by their general practitioners, with all the associated benefits. PMID- 8219918 TI - von Willebrand factor and the endothelium in vascular disease. AB - von Willebrand factor (vWF), first described in a bleeding disorder, has numerous other roles, some of which can be viewed in terms of the pathogenesis of atherosclerosis and others in the formation of thrombus. As a marker of endothelial cell injury it provides a unique opportunity to observe the events involved in conditions where vasculitis may occur, e.g. inflammatory vascular disease and diabetes. Just as low levels predispose to disease, so excessively high levels may lead to adverse cardiovascular events such as myocardial infarction and femoral artery occlusion, which may both be precipitated by thrombus. It is possible that intervention (possibly with drugs, peptides or other agents) that reduces circulating vWF, perhaps by interfering with its activity in aggregating platelets and mediating their adhesion to the sub endothelium, or reducing its release from the endothelium, may lead to a reduction in thrombotic disease. PMID- 8219919 TI - Programmed cell death (apoptosis) in immunity and haematological neoplasia. AB - Programmed cell death, also commonly referred to as apoptosis, is a genetically controlled sequence of events, often requiring protein synthesis, which results in cell death. Although initially described 20 years ago, it is only recently that its role as a mechanism in controlling cell population size and content has been fully realised. In this review the biochemical events of apoptosis are discussed briefly, followed by a more detailed look at the role of programmed cell death in the control of haemopoiesis and the maintenance of a balanced functional immune system. The role of proto-oncogenes and suppressor genes known to regulate programmed cell death is covered, and also their influence on the induction and maintenance of neoplastic disease. Finally, the potential role of apoptosis in the resistance of haematological malignancies to chemotherapy is commented on. PMID- 8219920 TI - Drugs of abuse in urine: some pitfalls in testing. AB - Drugs of abuse are usually detected in urine samples-drugs of abuse in urine (DAU). Whilst DAU testing may be required in the clinical situation, it is also a potential source of income from (e.g.) pre-employment medical examinations. DAU test results can, therefore, quite easily become the subject of legal debate. These points are discussed, along with an overview of the documentation procedures necessary should a laboratory decide to offer this service, and a brief survey of the screening and confirmatory testing procedures available. PMID- 8219921 TI - Serum sialic acid enzymatic assay based on microtitre plates: application for measuring capillary serum sialic acid concentrations. AB - We have adapted a commercially-available kit for the enzymatic determination of sialic acid so that the reaction can be carried out in microtitre wells and the coloured end product quantitated on an ELISA plate reader. The small volume of serum used allows sialic acid to be measured in capillary blood samples. The assay was based on release of sialic acid from glycoconjugates by neuraminidase, cleavage of sialic acid by N-acetyl neuraminic acid aldolase to pyruvate, and then oxidation of pyruvate to hydrogen peroxide by pyruvate oxidase. Hydrogen peroxide was determined by the red product formed in the presence of peroxidase, 4-aminoantipyrine and N-ethyl-N-2-hydroxyethyl-3-toluidine. The assay was linear to at least 10 mmol/l and unaffected by haemolysis, and by the addition of glucose, 3-hydroxybutyrate, bilirubin and pyruvate. Capillary serum sialic acid concentrations were not significantly different from simultaneously measured venous serum sialic acid levels. Self-collected capillary blood samples were obtained from healthy subjects over 6 h during the day. No variations in serum sialic acid concentrations were found in response to a meal. We conclude that this micro-adaptation of a specific sialic acid assay will be suitable for epidemiological surveys of serum sialic acid collected by patients and normal subjects. PMID- 8219922 TI - Performance evaluation tests of new laboratory procedures or devices: practical reporting criteria. AB - The publication of papers reporting evaluations of new laboratory procedures and devices has increased rapidly in recent years. As more commercial systems emerge in the market place, and laboratory-based systems disappear, the potential user of the new system turns to his peers for opinions about the function of such systems. Unfortunately, many published reports lack statistical guidance and the reader is too often faced with a recitative about percentage differences and probabilities of significance, frequently reported on unacceptably small sample numbers. This communication offers guidance to those seeking to produce evaluation reports that will be of practical value to others. PMID- 8219923 TI - Immunocytochemical quantitation of inflammatory cells associated with Helicobacter pylori infection. AB - Inflammatory cells in Helicobacter pylori-associated gastritis (HAG) were quantified. The results were compared with the gastric biopsy samples from patients with non-Helicobacter pylori gastritis (non-HAG). In order to detect immunocytochemically sensitive antigens, the biopsy samples were acetone-fixed at -20 degrees C and processed into glycol methacrylate at 4 degrees C. Parallel routine biopsy samples were formalin-fixed and paraffin-embedded. A larger, more selective retrospective study was also established examining routinely processed gastric biopsy samples. The results of both studies were expressed as numbers of individual cell types/mm2 of gastric mucosa, and showed that neutrophil granulocytes were significantly increased in HAG whereas T-lymphocytes were not. Heli. pylori colonisation was associated with a significant increase of CD8 positive lymphocytes in the epithelium of the crypts. PMID- 8219924 TI - Genital mycoplasmas revisited--an evaluation of a new culture medium. AB - The role of genital mycoplasmas as pathogens causing severe neonatal respiratory and central nervous system disease has been highlighted recently following publication of new data. These organisms are generally neglected by diagnostic laboratories in the United Kingdom, possibly due to the lack of a suitable commercially-available culture medium. We have evaluated the bioMerieux Mycoplasma-Lyo system using qualitative and quantitative studies and have found it to have suitable qualities and practical advantages for detection of Ureaplasma urealyticum and Mycoplasma hominis. PMID- 8219925 TI - Brain and atrial natriuretic peptide plasma concentrations in normal healthy children. AB - Specific radioimmunoassay techniques were used to measure simultaneously plasma levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in normal healthy children and adults. The concentrations of BNP in plasma of 20 children (mean +/- SEM; 31 +/- 4 pg/ml) were significantly higher (P < 0.05) than concentrations in plasma of 20 adults (12 +/- 1.8 pg/ml). There was no significant difference in levels of plasma ANP between children (27 +/- 3 pg/ml) and adults (36 +/- 2.2 pg/ml). Plasma levels of BNP were positively correlated with plasma ANP levels in children (r = 0.53, P < 0.02, n = 20) and in adults (r = 0.59, P < 0.02, n = 20). These results suggest that plasma levels of BNP in normal children are higher than levels in normal adults; and provide a useful baseline for comparison with levels of BNP and ANP in plasma of children with impaired cardiac function. PMID- 8219926 TI - External quality assessment of the full blood count, and problems associated with the use of fixed blood preparations. AB - The experience of using a stored fixed blood preparation for external quality assessment of the full blood count is described. Differences between instruments employing differing technologies are highlighted and the problems of the control of the white cell differential count discussed. PMID- 8219927 TI - The efficacy of preoperative analgesic administration for postoperative pain management of pediatric dental patients. AB - Appropriate pain-management strategies for children receiving dental care continue to be poorly delineated. Recent studies have demonstrated the benefit of preoperative analgesic administration upon alteration of the postoperative pain experience in adults. It is the purpose of this study to assess the efficacy of preoperative administration of acetaminophen on the prevalence of postoperative pain-related behaviors and the frequency of postoperative analgesic use in 4- to 10-year-old children following various dental procedures. The results indicate a high prevalence of postoperative pain, independent of the type of dental procedure performed and the preoperative administration of acetaminophen. There is a trend toward reduced postoperative pain in the acetaminophen pretreatment groups. A greater sample size, with more reliable pain-assessment methods, may help to further elucidate the efficacy of preoperative analgesic administration in children. The clinician should be alerted to the potential for pain-related behaviors to occur following routine pediatric dental care. PMID- 8219928 TI - Physical evaluation and the prevention of medical emergencies: vital signs. AB - It was assumed that dentists employ a complete system of physical evaluation for all new patients in their dental practices. Results of a survey of 1,588 dentists demonstrated that the use of a written medical history questionnaire was commonplace; however, recording of blood pressure and heart rate and rhythm on all new patients was quite limited. A greater percentage of dentists monitored blood pressure when there was a history of cardiovascular disease or high blood pressure. Monitoring of the heart rate and rhythm, even in patients with cardiovascular disease or high blood pressure, was severely limited in scope. A significant number of dentists still employ racemic epinephrine impregnated gingival retraction cord, and of these, 40% had observed "epinephrine-reactions." PMID- 8219929 TI - Global differences: philosophy to technique. PMID- 8219930 TI - Circulatory effects of vasoconstrictors combined with local anesthetics. AB - Vasoconstrictors are clinically used as adjuvants to local anesthetics to improve anesthetic action and to minimize local bleeding. Accidental intravascular injection or rapid systemic absorption of vasoconstrictors can induce a number of potentially life-threatening circulatory risks, which are described in this paper. PMID- 8219931 TI - An anaphylactoid reaction following local anesthesia: a case report. AB - A case report of an adverse reaction to a preparation of an amide local anesthetic, prilocaine with epinephrine, is presented. Signs and symptoms were consistent with an anaphylactic reaction and the patient responded positively to treatment based on this assumption. Treatment included administration of epinephrine injected sublingually and oxygen by inhalation. However, subsequent skin testing failed to confirm this diagnosis. A number of explanations are possible and a final diagnosis of an anaphylactoid reaction was made. Local anesthetic allergies and their management are reviewed. The literature demonstrates that an allergic reaction to amide local anesthetics can occur and a thorough history, intradermal testing, and subcutaneous challenge are reasonable approaches to determine a safe agent for subsequent use. PMID- 8219932 TI - Tolerance to intravenous midazolam as a result of oral benzodiazepine therapy: a potential problem for the provision of conscious sedation in dentistry. AB - Tolerance to the sedative effects of the benzodiazepine group of drugs is well documented. A brief review of the literature is presented. Three cases in which tolerance to intravenous midazolam became apparent and caused a significant problem during the attempted induction of conscious sedation are described. The patients were all concurrently receiving treatment with other benzodiazepines. It is recommended that patients with a history of regular, current benzodiazepine use be treated with caution with regard to this type of sedation. PMID- 8219933 TI - Intravenous sedation for third molar surgery. AB - The surgical removal of third molars is a frequently carried out procedure under day-stay general anesthesia. Economic considerations and the demand on hospital facilities together with the reduced incidence of morbidity suggest that intravenous sedation is an excellent alternative modality. Thirty cases of third molar surgery with intravenous sedation are described wherein excellent operating conditions and reduced morbidity are reported. PMID- 8219934 TI - Urinary collagen crosslink excretion: a better index of bone resorption than hydroxyproline in Paget's disease of bone? AB - The 24 h urinary excretion of the collagen degradation products pyridinoline (Pyr) and deoxypyridinoline (Dpyr) have been proposed as specific and quantitative indices of bone resorption. We compared the value of the urinary excretion of Pyr and Dpyr to that of hydroxyproline (OHP) in 11 patients with Paget's disease of bone before and during treatment with inhibitors of bone resorption, during admission to a metabolic ward and maintenance on a gelatin free diet. Pyr and Dpyr excretion rates were significantly correlated with those of OHP (r = 0.81 and 0.77, respectively, P < 0.001; n = 106). The rate and degree of suppression of bone resorption were monitored in 6 of the patients similarly treated with intravenous dimethyl-APD at a dose of 4 mg/day for 10 days, by daily measurements of the 24 h urinary excretion of Pyr, Dpyr and OHP. Treatment with dimethyl-APD resulted in a decrease in the three indices of bone resorption. The percentage change from baseline values was similar for the three indices, although changes in Dpyr appeared to follow more closely those of OHP. Our findings suggest that Pyr and Dpyr are useful and specific indices of bone resorption in Paget's disease of bone. They appear to confer no advantage, however, over the traditional determination of the urinary excretion of OHP, in the monitoring of response to treatment of such patients with inhibitors of bone resorption. Further studies are required to establish the value of these new biochemical indices of bone resorption, possibly in more subtle disorders of bone metabolism such as osteoporosis. PMID- 8219935 TI - Effects of short-term low-dose heparin administration on biochemical parameters of bone turnover. AB - Heparin therapy may cause osteoporosis. The effects of short-term low-dose heparin are not known. We have studied the effects of short-term heparin administration, twice daily 5000 IU s.c., for 10 days on the biochemical parameters of bone turnover in six healthy male volunteers. No effects were observed on the urinary excretion of hydroxyproline and calcium. Serum levels of cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), a new marker of bone resorption, did not change significantly. A slight but significant decrease in serum alkaline phosphatase was observed. TmP/GFR increased significantly during heparin administration. In all volunteers a uniform increase in serum transaminases appeared which completely reversed after discontinuation of heparin administration. We conclude that short-term low-dose heparin administration does not change biochemical parameters of bone resorption, but has a small significant suppressing effect on serum alkaline phosphatase levels. Heparin administration resulted in a significant but transient increase of serum transaminase levels. PMID- 8219936 TI - 'Mucoid dissolution' of bones and multiple pathologic fractures in a patient with past history of intravenous administration of polyvinylpyrrolidone (PVP). A case report. AB - Polyvinylpyrrolidone (PVP) has been used in industry as well as in medicine for various purposes, e.g. as a component of hair-sprays, 'retardant' for subcutaneous injections, and given intravenously as a plasma expander. The latter usage results in deposition of PVP in the reticulo-endothelial system and other mesenchymal cells, including osteocytes. A middle aged woman in Taiwan, who for 10 years received repeated intravenous injections of PVP, suffered pathologic fractures of both femora and her right humerus with additional destructive lesions seen radiologically in other bones. Biopsies of the fracture sites showed both intracellular PVP deposits and mucoid changes in the involved cells, a characteristic secondary complication of PVP deposition. This phenomenon, if of sufficient severity, may cause, as in this case, a virtual 'melting down' of osseous tissue with pathological fractures as a consequence. PMID- 8219937 TI - The release of tissue inhibitor of metalloproteinases by calvarial bone explants and its immunolocalization. AB - Tissue inhibitors of metalloproteinases (TIMPs) play an important role in the regulation of the activity of matrix metalloproteinases (MMPs) such as collagenase, stromelysin and gelatinase. Although it has been shown that upon culturing bone tissue releases relatively large amounts of TIMP, little is known as to the source of the inhibitor. In an attempt to investigate this in more detail calvarial bone explants from young rabbits were cultured in serum-free medium. The explants were cultured with or without adhering periosteum. In some experiments solitary periosteal fragments were maintained in the absence of bone. Media were analyzed for the presence of TIMP by immunoblotting and ELISA as well as for their capacity to inhibit the activity of collagenase. In addition, TIMP was immunolocalized in cryosections of the explants. The data demonstrated that bone-conditioned medium contained significantly more (2-10 times) collagenase inhibitor than periosteum-conditioned medium. Removal of the (convex and/or concave) periosteum from the calvariae did not significantly affect the amount of inhibitor released. Immunoblots and ELISA showed the presence of TIMP in the media, being more in bone- than in periosteum-conditioned medium. In immunolabeled cryosections TIMP appeared to be present in osteoblast-like cells lining both the outer bone surface as well as the endosteal spaces. Label was also found in a number of osteocyte lacunae. The periosteum was almost negative. It is suggested that TIMP contributes to the regulation of MMP-activity involved in the remodeling and turnover of bone. PMID- 8219938 TI - Precision and accuracy for rat whole body and femur bone mineral determination with dual X-ray absorptiometry. AB - Precision and accuracy for rat whole body and excised femur bone mineral density (BMD) measurements were evaluated with two dual X-ray absorptiometry (DXA) systems. The 'small subject' mode on the Norland XR-26 (XR), and the 'ultra high resolution mode' on the Hologic QDR-1000/W(QDR) were used for the analysis. The whole body mode was only available on the XR. The lowest precision error for the whole body was found using a scan resolution of 1.0 x 1.0 mm and a scan speed of 15 mm/s. The scan spatial resolution of the femur measurement was approximately eight times higher on the QDR than on the XR. However, the XR allowed analysis of an arbitrary region of interest within the femur, which was not easily done with the QDR. Precision for the total femur measurement on the QDR (0.5-0.9%) was approximately two to four times superior to that of the XR (1.5-4.3%). The difference may be due to the superior scan resolution of the QDR. Bone mineral content and BMD on the QDR significantly declined with an increase of water depth (P < 0.001). No significant change was observed on the XR. Both DXA systems demonstrated an excellent correlation (r > or = 0.98) with ash weight under the scan conditions examined. The optimal scan condition for the excised femur measurement on the XR was obtained with 1.5-2.5 cm of perspex or water and a scan speed of 10 mm/s. For the QDR, we recommend scanning the rat femur with approximately 2.5 cm of perspex or water in terms of precision and accuracy. PMID- 8219939 TI - Evaluation of a model for prediction of lumbar bone mineral density. PMID- 8219940 TI - Influence of aging and menopause in determining vertebral and distal forearm bone loss in adult healthy women. AB - In order to assess the relative influence of aging and menopause in determining the decrease of bone mass in adult women, two groups of normal subjects were examined in this retrospective, cross-sectional study. In group A, bone mineral density (BMD) was evaluated at spine (L2-L4) by dual X-ray absorptiometry (DXA) (Hologic QDR-1000); in group B, BMD was measured at the distal forearm by single photon absorptiometry (SPA) (Osteometer DT 100). Both groups were further divided into two subgroups: A1 and B1 included women with the same postmenopausal, but different chronological age; A2 and B2 included women with the same chronological, but different postmenopausal age. BMD and BMI-corrected BMD (cBMD) were plotted versus age and years since menopause, respectively. Mathematical analysis of the correlation curves between BMD and chronological age showed that the decrease of BMD is very similar at spine and forearm, and is better fitted by a quadratic function. Age-related fractional bone diminution shows a progressive increase with aging (at spine: -0.38%/year at 45 years, -0.81%/year at 50, 1.3%/year at 55 and -1.9%/year at 60. At forearm: -0.5%/year at 50 years, 1.1%/year at 55 and -1.68%/year at 60). On the other hand, menopause-related BMD decrement is very evident during the first year since menopause (at spine: 8.1%/year; at forearm: -3.4%/year), and progressively decreases, according to a logarithmic function. Ten years later, yearly diminution of BMD is below 1%/year and 0.4%/year at spine and forearm, respectively. At this time, age contributes to determine bone loss for 2/3 and menopause for 1/3. PMID- 8219941 TI - The psychology of multiple allergy. PMID- 8219942 TI - Death from occupational disease. PMID- 8219943 TI - Public opinion and the NHS. PMID- 8219944 TI - Health care reform: the global search for utopia. PMID- 8219945 TI - Tuberculosis and poverty. AB - OBJECTIVE: To examine whether the historical link between tuberculosis and poverty still exists. DESIGN: Retrospective study examining the notifications of all forms of tuberculosis by council ward over a six year period and correlating this with four indices of poverty; council housing, free school meals, the Townsend overall deprivation index, and the Jarman index. SETTING: The 33 electoral wards of the city of Liverpool. SUBJECTS: 344 residents of Liverpool with tuberculosis. RESULTS: The rate of tuberculosis was correlated with all measures of poverty, the strongest correlation being with the Jarman index (r = 0.73, p < 0.0001). This link was independent of the high rates of tuberculosis seen in ethnic minorities. CONCLUSION: Tuberculosis remains strongly associated with poverty. PMID- 8219946 TI - Investigation of urinary tract infection in childhood. AB - OBJECTIVES: To determine the number of laboratory confirmed urinary tract infections in children and to ascertain general practitioners' practices and attitudes towards their investigation and management. DESIGN: Prospective one year survey of urine specimens submitted for bacteriological investigation; review of radiology department records; questionnaire survey of general practitioners. SETTING: Gloucester health district. SUBJECTS: 57,432 children aged < 15 and 7143 children aged < 2 registered with a general practice in Gloucester health district and their 195 general practitioners. RESULTS: 4317 urine specimens were submitted from children aged < 15, of which 563 from 442 children were culture positive. The rate (number/100 children/practice) of culture positive urine specimens in these children varied more than 10-fold between general practices, and this correlated closely with the rate of referral of urine specimens for investigation. A follow up specimen to check for clearance of infection was taken in 22% (125/563) of infections. Of the 821 specimens submitted from children aged < 2, 103 from 89 children were positive. Of these children, 28 underwent radiological imaging. Most general practitioners would aim to obtain bacteriological confirmation of urinary tract infection on weekdays but only a minority said they would do so at weekends. They were apparently more likely to refer boys and younger children for renal tract imaging after a first urinary tract infection. CONCLUSIONS: Urinary tract infection in children was underdiagnosed, and after a confirmed infection only a minority of patients received renal tract imaging or microbiological follow up. Greater awareness of the importance of investigation and management of urinary tract infection in children is needed, and the practical difficulties faced by general practitioners must be resolved. PMID- 8219947 TI - Chronic constipation in long stay elderly patients: a comparison of lactulose and a senna-fibre combination. AB - OBJECTIVES: To compare the efficacy and cost effectiveness of a senna-fibre combination and lactulose in treating constipation in long stay elderly patients. DESIGN: Randomised, double blind, cross over study. SETTING: Four hospitals in Northern Ireland, one hospital in England, and two nursing homes in England. SUBJECTS: 77 elderly patients with a history of chronic constipation in long term hospital or nursing home care. INTERVENTION: A senna-fibre combination (10 ml daily) or lactulose (15 ml twice daily) with matching placebo for two 14 day periods, with 3-5 days before and between treatments. MAIN OUTCOME MEASURES: Stool frequency, stool consistency, and ease of evacuation; deviation from recommended dose; daily dose and cost per stool; adverse effects. RESULTS: Mean daily bowel frequency was greater with the senna-fibre combination (0.8, 95% confidence interval 0.7 to 0.9) than lactulose (0.6, 0.5 to 0.7; t = 3.51 p < or = 0.001). Scores for stool consistency and ease of evacuation were significantly higher for the senna-fibre combination than for lactulose. The recommended dose was exceeded more frequently with lactulose than the senna-fibre combination (chi 2 = 8.38, p or = 0.01). As an index of the standard daily dose, the dose per stool was 1.52 for lactulose and 0.97 for the senna-fibre combination, at a cost per stool of 39.7p for lactulose and 10.3p for senna-fibre. Adverse effects were no different for the two treatments. CONCLUSIONS: Both treatments were effective and well tolerated for chronic constipation in long stay elderly patients. The senna-fibre combination was significantly more effective than lactulose at a lower cost. PMID- 8219948 TI - Problems in assessing contents of metered dose inhalers. PMID- 8219949 TI - Smoking and periductal mastitis. PMID- 8219950 TI - Colourings, flavourings, and sugars in children's medicines in India. PMID- 8219951 TI - Age of exposure to infections and risk of childhood leukaemia. PMID- 8219952 TI - Impact of introducing near patient testing for standard investigations in general practice. AB - OBJECTIVE: To assess the clinical and economic impact of surgery based near patient testing in general practice for six commonly used biochemical and bacteriological tests. DESIGN: After four months' monitoring, equipment for two bacteriological and four biochemical tests was introduced without cost into 12 practices using a crossover design. Structured request forms were used to monitor laboratory investigations. SETTING: 12 general practices in west midlands and south west Thames with list sizes above 9000. MAIN OUTCOME MEASURES: Investigation rates per 1000 consultations. Changes from baseline rates. Reasons for requesting investigations and provisional diagnoses. Cost per test and sensitivity of costs to rate of use. RESULTS: Investigation rates for the six tests rose by 16.5% (from 78.6/1000 consultations to 91.6/1000) when equipment was available in the surgery and reverted to baseline rates when it was withdrawn. The average weekly number of tests when equipment was available ranged from 0.5 to 10.5 (mean 9.0). Cholesterol tests were used as an addition to laboratory testing, usually for screening. Midstream urine analysis was often done in the surgery instead of in the laboratory, although 30% of samples were tested by both methods. Doctors' reasons for investigation and conditions tested were largely unaffected by availability of surgery tests. Costs for surgery tests were higher for all tests except midstream urine. CONCLUSIONS: Availability of surgery based testing increased the number of tests performed. It was cost effective only for midstream urine analysis. PMID- 8219953 TI - Alzheimer's disease. PMID- 8219954 TI - Health care in Moscow. AB - In the Russian Federation privatisation is affecting the health care sector as much as it is industry and commerce. That the general public support the transfer of state clinics to the private sector is a mark of their dissatisfaction with the old state run system. Doctors too see better opportunities to practise good medicine and be paid better for doing so. In Moscow the health department has set up a commission to license all clinics providing treatment, which should ensure standards of safety, training, and equipment. The Russian Federation is also trying to establish a medical insurance system to cover its citizens for health care, but in Moscow and elsewhere its implementation has been delayed by arguments and bureaucracy. In the meantime the health of Muscovites remains poor, with a high incidence of birth defects, and illnesses among the young. PMID- 8219955 TI - ABC of emergency radiology. Cervical spine--I. PMID- 8219956 TI - Controversies in treatment: Should a sexual offender be allowed castration? PMID- 8219957 TI - Cost-effectiveness analysis. AB - When different health care interventions are not expected to produce the same outcomes both the costs and the consequences of the options need to be assessed. This can be done by cost-effectiveness analysis, whereby the costs are compared with outcomes measured in natural units--for example, per life saved, per life year gained, and per pain or symptom free day. Many cost-effective analyses rely on existing published studies for effectiveness data as it is often too costly or time consuming to collect data on cost and effectiveness during a clinical trial. Where there is uncertainty about the costs and effectiveness of procedures sensitivity analysis can be used, which examines the sensitivity of the results to alternative assumptions about key variables. In this article Ray Robinson describes these methods of analysis and discusses possibilities for how the benefits of alternative interventions should be valued. PMID- 8219958 TI - Deciding who needs thrombolysis. A normal ECG means better prognosis. PMID- 8219959 TI - Deciding who needs thrombolysis. Reserve thrombolysis for patients who would benefit. PMID- 8219960 TI - Deciding who needs thrombolysis. Validation of ECG diagnosis inadequate. PMID- 8219961 TI - Deciding who needs thrombolysis. Disappearing ST elevation could mean reperfusion. PMID- 8219962 TI - Deciding who needs thrombolysis. Domiciliary ECGs unreliable. PMID- 8219963 TI - Changing childbirth. Antenatal care must be shared. PMID- 8219964 TI - Changing childbirth. Domino schemes preferable to team midwifery. PMID- 8219965 TI - Drug treatment during Ramadan. Don't be complacent about diabetes. PMID- 8219966 TI - Funding policies for HIV and AIDS. Need more and better information. PMID- 8219967 TI - Funding policies for HIV and AIDS. GPs should be more involved. PMID- 8219968 TI - Funding policies for HIV and AIDS. Patients benefit from shared care. PMID- 8219969 TI - Muscle cramps during prednisolone treatment. PMID- 8219970 TI - Mental health professionals favour community supervision orders. PMID- 8219971 TI - Risk of Creutzfeldt-Jakob disease in bodybuilders. PMID- 8219972 TI - Underenumeration in the 1991 census. PMID- 8219973 TI - Forced hyperventilation increases blood pressure. PMID- 8219974 TI - Distribution of mental health professionals in primary care. PMID- 8219975 TI - Protecting the public. PMID- 8219976 TI - Care of suicidal prisoners. ...and a last resort. PMID- 8219977 TI - Care of suicidal prisoners. Deliberate self harm is underreported. PMID- 8219978 TI - Care of suicidal prisoners. Use of unfurnished rooms is exceptional... PMID- 8219979 TI - HIV and insurance. PMID- 8219980 TI - [The behavioral and neurochemical changes in rats caused by the subchronic administration of haloperidol]. AB - Rat experiments showed that subchronic haloperidol enhanced or perverted motor asymmetry appearing in response to apomorphine, resulted in imbalance between the dopaminergic and serotoninergic systems and increased norepinephrine levels. It was concluded that intra- and interhemispheric imbalance might be one of the causes of extrapyramidal disorders associated with the long-term administration of the neuroleptic. PMID- 8219981 TI - [The dynamic circadian mobility of rats under acute and chronic propranolol administration]. AB - Acute administration of propranolol, 1 mg/kg i.p., decreased the amplitude of locomotor circadian rhythm in rats and shifted its acrophase to late night hours. After chronic (10-day) treatment with the drug, morning rises in locomotion after turning out the light became less frequent. The circadian rhythm reorganization observed may depend on the effects of the beta-adrenoblocker on its specific receptors in the hypothalamic suprachiasmatic nuclei and/or the pineal gland. PMID- 8219982 TI - [The participation of adren-, cholin- and dopaminergic mechanisms in the development of hyperbaric nitrogen narcosis in rabbits]. AB - Behavior and EEC responses to electrical stimulation of the frontal cortex (FC), mesencephalic reticular formation (MERF), dorsal hippocampus (DH), and nucleus caudatus (NC) were investigated in hyperbaric experiments on rabbits. As compared to the control data, the thresholds of motor reaction caused by the stimulation of FC and MERF in N2/O2 mixture at 11 ATA were increased by 41% (p < 0.05) and 10% (p < 0.05), respectively, whereas those by DH and NC stimulation showed no changes as compared to the controls. During decompression to 5 ATA, the thresholds of intracranial stimulation of FC and MERF returned to the control level. After prior injection of pharmacological agents that activated or inhibited the adren-, dopamin-, and cholinergic neurotransmitter systems, different changes in behavior, EEC, and stimulation thresholds were observed in N2-O2 under high pressure. The application of the adrenergic activator ephedrine may be promising in pharmacologically correcting nitrogen narcosis. PMID- 8219983 TI - [The nonuniform sensitivity of the cerebral vessels to serotonin]. AB - With serotonin, cerebral blood flow decreased to a great degree during multiple injections. Serotonin was found to produce different effects on brain arterial vessels. It enhanced the resistance of carotid arteries to a greater degree than that in the cerebrobasilar system. Serotonin constricted pial arterioles with an initial diameter of more than 40 nm, whereas the microvessels of less diameter got substantially dilated. The agent had a depriming effect on somatosympathetic and vasomotor reflexes via its interaction with central noradrenergic structures. PMID- 8219984 TI - [The long-term use of antihypoxants in myocardial infarct in rats: their effect on the hemodynamics and contractile function of the heart]. AB - In the experiments in rats with myocardial infarction induced by left coronary occlusion, effects of antihypoxants were studied during their long-term intraperitoneal injection (daily once during 21 days) on hemodynamics and myocardial contractility. Sodium oxybutyrate, 200 mg/kg, piracetam, 400 mg/kg, and glyo-6, 100 mg/kg, were shown to exert no significant effects on cardiac contractility at rest, however during exercise they normalized aortic blood flow acceleration. The antihypoxants increased the survival of rats with myocardial infarction. PMID- 8219986 TI - [The effect of a crown-ether derivative, ethmozine and etatsizin on the functioning of the calcium pools in the guinea pig myocardium]. AB - Analysis of the component structure of single contractions of papillary muscles in guinea pigs was used to study the effects of the crown ether derivative benzylase-15-crown-5 and the antiarrhythmic agents ethmozine and ethacizine. The negative inotropic effect of these compounds was shown to be associated with limited penetration of calcium ions from the sarcolemmal pool into cardiac cellular myoplasm. PMID- 8219985 TI - [The antiarrhythmic activity of the polymeric forms of quinidine, trimecaine, etatsizin, propranolol and verapamil]. AB - The antiarrhythmic activity and acute toxicity of polymeric formulations of quinidine, trimecaine, ethacizine, propranolol, verapamil which had been immobilized on a cellulose carrier (monocarboxylcellulose) and low molecular analogues were studied in various experimental animals (rats, mice, dogs). The polymeric formulations of trimecaine and verapamil were found to have a higher antiarrhythmic activity in different arrhythmia models than trimecaine and verapamil. The toxicity of all new compounds was no more than the values of conventional antiarrhythmic drugs. PMID- 8219987 TI - [The relationship between the magnitude of the negative inotropic action and chemical structure of crown-ether derivatives]. AB - The relationship between the inotropic effect and chemical structure of 15-crown 5 and 18-crown-6 derivatives was studied in experiments in open-chest anaesthesized cats, by using computer-aided analysis. The findings showed that the 15-crown-5 derivatives produced more pronounced cardiotropic effect and they were less toxic than 18-crown-6 derivatives. Computer-aided analysis revealed pharmacophoric groups which are responsible for cardiotropic (negative inotropic) activity in the series of crown ether derivatives. PMID- 8219988 TI - [The effect of cerebrocrast on erythrocyte function]. AB - The new calcium antagonist cerebrocrast intravenously infused in a dose of 0.4 micrograms.kg-1.min-1 during 15 min prevented erythrocyte deformability disturbances at the end of cerebral ischemia in rats, which was induced by carotid artery occlusion during 30 min. The agents also prevented the deformability 1 hour after the onset of recirculation. Cerebrocrast reduced spontaneous erythrocyte aggregation, the strength of erythrocytic aggregates, and hemoglobin affinity for oxygen. The latter effect was associated with the drug induced increase in erythrocytic 2,3-diphosphoglycerate levels. PMID- 8219989 TI - [The effect of solubilized methandrostenolone on muscle hypertrophy and on the blood biochemical indices in rats]. AB - The paper outlines a new mode of intravascular anabolic steroidal transport. The single intravenous administration of metandrostenolone aqueous solution to rats increases hypertrophy rate of MM. plantaris. It was shown that the action of a single dose (0.05 mg/kg) exceeded that of metandrostenolone oil solution in a dose of 5 mg/kg. The multiple reduction of doses of the anabolic drug and the high level of bioavailability were achieved. This effect was explained by the application of the specific transport agent. PMID- 8219990 TI - [Essentiale as an inducer of immunomodulating properties in erythrocytes]. AB - The erythrocytes extracorporeally treated with essentiale have a property to stimulate an immune response to T-dependent antigen, but fail to affect the extent of the immune response induced by T-independent antigen. The treatment of essentiale induces the appearance of immunostimulating properties in a fraction of heavy (over 1.117) erythrocytes, but does not influence the properties of light (under 1.079) and intermediate (1.092-1.105) erythrocytes. The essentiale modified heavy erythrocytes induce intact rat splenic cell adherent to the glass to release the factor that stimulates an immune response to T-dependent antigen and the factor that induces the appearance of immunosuppressor properties of light erythrocytes. PMID- 8219991 TI - [The immunoactive properties of trekrezan]. AB - It was shown that in vivo trecrezan possessed strong immunoactive properties: it decreased the spot-forming activity of polypotent stem blood cells, stimulated lympho- and hemopoesis, antibody formation, possessed steady antiinflammatory activity. It stimulated in vitro mononuclear cell proliferation in man due to its direct action on B lymphocytes and increase in lymphokine and monokine production. PMID- 8219992 TI - [The free-radical mechanisms of the cytotoxic action of 1,2-benzoquinone derivatives]. AB - The authors examined the interaction of 1,2-benzoquinone derivatives with HeLa cell cultures and ascite Ehrlich's cancer cells. 4-N (anilino)-5-methoxy-1,2 benzoquinone was found to produce a marked toxic effects against tumor cells. The cytotoxic effect is oxygen dependent and associated with the formation of oxygen radicals in quinone's redox cyclization reactions. The inhibitory analysis was used to show that the major mediators of the toxic action of the agent are superoxide radical-anion and hydrogen peroxide. It is concluded that the interaction of highly toxic oxygen radicals, which are generated in quinone redox cyclization, with plasma membrane cells is likely to be the mechanism responsible for cellular destruction when quinones act on tumor cells. PMID- 8219993 TI - [The effect of epiphysectomy on the power of hexenal to alter the EEG spectral characteristics over a transitional 24-hour period]. AB - In pinealectomized rats, in the morning (06.00-09-00) the ability of hexobarbital sodium, 60 mg/kg i. p., to increase cortical and hippocampal EEG spectral characteristics was significantly enhanced. On the contrary, in the evening (18.00-21.00) it was decreased. These changes may be associated with pineal gland involvement in circadian rhythm. PMID- 8219994 TI - [The toxicity of different forms of 24,25-dihydroxycholecalciferol preparations in rats]. AB - The purpose of the study was to examine the toxicity of 24,25-DOXK on calcium phosphorus metabolic parameters. The rats from experimental groups received enteral 50- and 1,000-fold physiological doses of 24,25-DOXK (Vitamins Research Production Association) as a combination of R- and S-epimers and homogeneous R epimer in sunflower oil solutions or ethanol mixture (1:4 propylene glycol) during 3 and 7 days. Though there was a stable tendency for hyperphosphatemia and altered blood calcium concentrations, the 24,25-DOHK formulations under test, unlike 1-OXK and 1,25-DOXK, displayed no toxic properties on the kidney, heart and aorta and produced a mineralizing effect on bone tissue in the acute period. Comparison of the properties shown by 24R,25-DOXK and 24R,S-DOXK showed that a combination of 24,25-DOXK R- and S-epimers was preferable for practical application. PMID- 8219995 TI - [The testing of the carcinogenicity of dispirotripiperazine derivatives by combined administration with sodium nitrite]. AB - The cancerogenic activity of the dispirotripiperasinium derivatives prospidine and spirobromine was tested in concurrent use with sodium nitrite. The drugs were intragastrically administered once a week. It was combined with sodium nitrite, 35 mg/kg, to non-inbred rats of both sex during 24 months. A morphological study revealed no statistically significant reduction of latency and no increase in the incidence of tumors in laboratory animals. No cancerogenic effect of sodium nitrite was found. PMID- 8219996 TI - [An evaluation of the skin-resorptive action of dimephosphon when used locally long term]. AB - Experiments in rabbits and rats established that 15% dimephosphonum solution after its topical (skin) application over a long period of time (2 and 6 months) exerted no toxic skin-resorption effects, reduced blood lipid and lipid peroxidation product levels. The substance of dimephosphonum after 6-month daily skin applications caused reversible changes in renal and adrenal functions. PMID- 8219998 TI - [A modification of the ortho-toluidine method for determining glucose in the blood]. AB - Modification of the orthotoluidine technique is associated with the necessity to examine blood glucose levels in mice, its dynamics analysis (by 5-6 points), which greatly expands the possibility of an experiment on screening new hypoglycemic agents. Addition of tert-butanol (isobutamol) facilitates the interaction of orthotoluidine with glucose, by enhancing the sensitivity and accuracy of the technique and allowing blood microquantities (10-20 microliters per determination) to be analysed. In terms of its accuracy and reliability, the proposed modification is not virtually inferior to expensive enzymatic techniques. The findings suggest that the modified orthotoluidine technique may be useful in the analysis of glucose levels in dynamics in small laboratory animals. PMID- 8219997 TI - [The characteristics of the wound-healing action of solubilized alpha-tocopherol acetate]. AB - The rat experiments were made to compare the wound-healing action of solubilized (aqueous) alpha-tocopherol acetate (SATA) prepared by the original techniques and its official oil-based preparation. A course intravenous SATA (2 mg four times at an interval of 4 days) administration was found to stimulate epithelial regeneration and suppress the formation of connective tissue of uncomplicated skin wounds. By healing the complicated wounds, SATA potentiated the occurrence of an inflammatory reaction and slowed down regeneration, whereas its oily solution failed to produce this effect. PMID- 8219999 TI - [A model for the experimental evaluation of the absolute bioavailability of drugs -weak organic bases]. PMID- 8220000 TI - [V. I. Nikol'skii (on the 70th anniversary of the death of this scientist)]. PMID- 8220001 TI - [Inducers of the liver mono-oxygenase system and the prospects for their clinical use]. PMID- 8220002 TI - [The effect of psychotropic preparations on the behavioral and hormonal manifestations of emotional stress in monkeys]. AB - Ethological and radioimmunological techniques were used to examine the effects of psychotropic agents on the behaviour of the male Papio hamadryas and the hormonal activity of the steroid-producing glands at physiological rest and during emotional stress. Prior (15 minutes before immobilization) intramuscular administration of haloperidol, 0.1 mg/kg, amitriptyline, 2.0 mg/kg or diazepam, 0.76 mg/kg, was demonstrated to produce no stress protective effect, but to result in predominant effects of these drugs in the poststress period, or even in enhanced stress-induced behavioral and hormonal changes. PMID- 8220003 TI - [Diuretic interaction with the renal kallikrein-kinin system]. PMID- 8220004 TI - [The genetic polymorphism of mephenytoin oxidation in man]. PMID- 8220005 TI - [The characteristics of the effect of imperialone on the M-cholinoreceptors of different organs]. AB - The pharmacological studies of the steroidal alkaloid imperialone have revealed its high M-cholinolytic activity on the heart, which was accompanied by sensibilization of M-cholinoreceptors in the secretory cells of lacrimal, salivary, and gastric glands and M-receptors in the smooth muscle of the intestine and urinary bladder. Bearing in mind the currently available data on M cholinoreceptors, imperialone can be regarded as M2-cholinolytics having M3- and M4-cholinopotentiating properties. Imperialone is a potent agent used for selective cardiac M2-receptor blockade and for enhancement of the functional activity of smooth muscle and secretory organs that have M3- or M4 cholinoreceptors. PMID- 8220006 TI - [The cerebral vasoconstrictor effects of malondialdehyde]. AB - Malonic dialdehyde has a pronounced central vasoconstrictor effect, though when given in large doses, it causes a profound decrease in systemic blood pressure, however its vasoconstrictor effects are not directly related to fluctuations in systemic blood pressure. The universal antioxidant alpha-tocopherol acetate abolishes and prevents the central vasoconstrictor effects of malonic dialdehyde. PMID- 8220007 TI - [Experimental and clinical studies of the action of verapamil (finoptin) on the cerebral circulation in transient cerebral ischemia]. AB - The experiments on unanesthetized rats have established that the intravenous injection of verapamil in a dose of 0.6 mg/kg during 30-minute carotid occlusion with subsequent recirculation prevents postischemic hypoperfusion, normalized oxidative processes and prevents brain tissue edema. In patients with transient cerebral circulatory disorders, a single injection of verapamil in a dose of 10 mg enhances the pulse filling of cerebral vessels. During a course therapy, the drug decreases minor and middle vessel tone, increases the REG amplitude, lowers the interhemispheric asymmetric blood filling rate, and enhances the functional resistance of cerebral vessels. PMID- 8220008 TI - [The participation of the prostacyclin-thromboxane system in the mechanism of the action of calcium antagonists]. AB - The experiments with isolated rat aortic circular segments have shown that vasocyclin (natural prostacyclin), verapamil, and diltiazem cause the relaxation of vascular smooth muscles during potassium-induced contracture. The impaired endothelium and acetylsalicylic acid-induced blockade of cyclooxygenase dramatically reduce the relaxant action of verapamil and diltiazem under these conditions. It is concluded that the system of prostaglandin synthesis plays an important role in the vasodilator effects of calcium antagonist. PMID- 8220009 TI - [The interrelationship of the arterial and venous sections of the systemic vascular bed under the action of verapamil and propranolol]. AB - Electromagnetic flowmetry and analogue computer techniques were used in the experiments on 12 anesthesized cats which indicated that verapamil increased cardiac output (CO) (due to lower afterload) and venous return (VR), distributed CO, by improving brain blood supply. The latter was due to more marked decrease in the vascular resistance of the brachiocephalic artery than that in the descending thoracic aorta. Propranolol diminished CO due to higher afterload, lower VR and cardiac pump function. At the same time blood flow in the brachiocephalic artery decreased to a lesser extent than that in the descending thoracic aorta. The blood flow changes in the great arteries, which were induced by the drug determined its use in the vena cava. PMID- 8220010 TI - [The future directions in the search for postsynaptic muscle relaxants with rapidly developing and short-term action]. PMID- 8220011 TI - [The influence of kordaron on the pharmacodynamic effects of strophanthin in experiments on isolated myocardial preparations and in the modelling of heart failure]. AB - The experiments with isolated rat atria isometrically contracting and those with simulated rat heart failure were performed to study the effects of the alpha-, beta-, and X-blocker cordarone on the pharmacodynamic effects of strophanthin. Cordarone was demonstrated to greatly decrease the toxicity of the cardiotonic in circulatory decompensation, without causing negative effects of cardiac inotropic function. Cordarone in combination with strophanthin slightly diminished the magnitude of the negative chronotropic effect of the cardiac glycoside and slowed down the rate of its cardiotonic effect. PMID- 8220012 TI - [The binding of furosemide and ethacrynic acid with different types of biological membranes]. AB - The study was undertaken to examine the effects of furosemide and ethacrynic acid on the fluorescence of 1,8-AHC in the suspension of erythrocytic membranes and lumenal and basolateral membranes of the rat renal epithelium. Ethacrynic acid was demonstrated to decrease probe luminescence in all three types of biological membranes. Furosemide failed to affect 1,8-AHC fluorescence in the suspension of blood ghosts and basolateral membranes of the renal epithelium and enhances probe fluorescence in the suspension of luminal membranes. The constants of binding of diuretics to the biological membranes were calculated. The effects of diuretics on the tryptophan fluorescence of renal epithelial luminal and basolateral membranes were studied in one of the series of experiments. It is suggested that the conformational rearrangements in the renal epithelial basolateral and luminal membranes can occur with ethacrynic acid. Furosemide in a dose of 10(-3) M showed the same effect only against luminal membranes. PMID- 8220013 TI - [An experimental study of sulprostone as an agent in preparation for abortion]. AB - The prostaglandin E sulprostone was studied in experiments on pregnant rats. It was shown to stimulate the bioelectrical activity of the uterus, by increasing the amplitude and frequency of biological potentials. Sulprostone was found to have abortive and embryotoxic effects which were especially pronounced during placentation. The drug induced a slight teratogenic effect. PMID- 8220014 TI - [The effect of merkazolil on the level of calcium-regulating hormones and 45Ca pharmacokinetics in rats]. PMID- 8220015 TI - [The effect of analgin on glucocorticoid receptors]. AB - Scatchard's analysis was used to examine the specific binding of 3H-acetonide of triamcinolone (3H-AT) by Type II glucocorticoid receptors of cytosol from the liver of Wistar rats weighing 180-200 g. It was found that analgin in concentrations of 5.0 and 10.0 mM inhibited the density of glucocorticoid receptors and increase the dissociate rate constant of 3H-AT from the receptor and decreased 3H-AT elimination half-life from the receptor. Analgin in concentrations of 0.04, 0.08, 0.16, 0.31, 0.62, 1.25, and 2.50 mM lowered the association constant of the 3H-AT-receptor complex in proportion to the increase of analgin concentrations. Analgin was found to have uncompetitive effects followed by inhibition of the density of Type II glucocorticoid receptors. PMID- 8220016 TI - [The virucidal properties of neoaquasept]. AB - The paper provides the evidence suggesting that the disinfectant neoaquasept (NA) obtained by using sodium salt of dichlorisocyanuric acid has virucidal activity against ectromelia virus in BALB/c mice. Three concentrations of NA were tested. The recommended application rate and concentration of the disinfectant is 3 and 10 times higher. NA was demonstrated to decrease the degenerative changes of the liver and spleen and increases the survival of the animals infected with ectromelia virus. It is proposed to use the water disinfected with NA as a preventive agent in the spread foci of various infections. PMID- 8220017 TI - [Theopek absorption efficiency in chronic diseases of the large intestine]. AB - A total of 10 patients with chronic ulcerative colitis (CUC) were examined. The patients took a single dose of theopec (300 mg). The patients with chronic obstructive lung diseases (COLD) without intestinal disorders served as controls. Blood theophylline concentrations were measured by high performance liquid chromatography. The absorptive efficiency of theopec was comparatively evaluated in patients with CUC and those with COLD without intestinal disorders. The use of the drug in patients with CUC resulted in the unneeded high serum theophylline concentrations. PMID- 8220018 TI - [The distribution of hematoporphyrin derivatives in the animal body]. AB - The pharmacokinetic distribution of haematoporphyrin derivative (HPD) and synthetic oligomeric haematoporphyrin (OG) which showed various lipophilicity was studied in animal tumor and normal tissues. The accumulation of dyes in tissue and their tumor-seeking capacity depended on the degree of polymerization, lipophilicity, and ratio of dye components. The difference in the absolute concentrations of HPD and OG (6.9 and 16.1 micrograms per g tissue, respectively) in tumor after dye injection in an adequate concentration (10 mg/kg b. w.) indicates that synthetic OG is beneficial for tumor diagnosis and photodynamic therapy. PMID- 8220019 TI - [Superoxide dismutase--a prospective hepatoprotective agent]. PMID- 8220020 TI - [The pharmacological properties of the triterpenoids from birch bark]. AB - The birch bark was used to prepare the summary triterpenic drug betulenol and its diacetate. Rat experiments with models of abnormalities revealed their hypolipidemic, cholagogic, antilithogenic and hepatoprotective activities which were higher than those found in the respective official drugs. PMID- 8220021 TI - [The systems analysis of the effect of piracetam, glycine and N-acetylglycinamide on long-term learning]. PMID- 8220022 TI - [The pigeon as an object for evaluating the activity of substances in vomiting of different origins]. PMID- 8220023 TI - [Low-molecular heparins: their mechanism of action, pharmacology and clinical use]. PMID- 8220024 TI - [Homeopathic preparations (the document compiled by an international group of experts)]. PMID- 8220025 TI - Infected intraabdominal hematomas: percutaneous drainage. AB - Percutaneous drainage of infected intraabdominal hematomas has often been contraindicated due to its greater number of complications. The results of percutaneous drainage of infected localized hematomas in five cases are described, two in the lesser sac and three in the right subphrenic space. The catheter size ranged from 8.4 to 24 French. Mean maintenance time of the drainage was 37 days. Drainage tube obstruction occurred in three patients, in two of whom the drainage tube had to be changed for one with a broader gauge. Hematomas were completely resolved in all the cases. We describe our experience with one patient in whom we used intracavitary urokinase who showed successful results. Percutaneous drainage is not contraindicated in the management of infected hematomas, although the drainage tube must be closely controlled; drainage time may be longer than in other types of abscesses. PMID- 8220026 TI - Confined gastric perforation: ultrasound and computed tomographic diagnosis. AB - A case of confined gastric perforation due to a penetrating antral ulcer diagnosed on ultrasound and computed tomography is presented. Air bubbles were visualized adjacent to the anterior gastric and bulbar wall, associated with small amounts of fluid in the subhepatic region and in the omental bursa. Careful examination of the subhepatic region and upper abdominal cavity in a patient with acute epigastric pain may lead to a correct diagnosis of such confined perforations. PMID- 8220027 TI - Compression filming with high-density barium suspensions. AB - A method is described for use of high-density barium suspension (250% wt/vol) during compression filming performed in conjunction with the double-contrast examination of the stomach. The technique employs control of the distribution of barium within the stomach by table tilting and use of the vertebral column to stabilize the posterior wall of the stomach. The technique allows routine demonstration of the area gastricae and gastric erosions on compression films, as well as detection of anterior wall lesions that may be undetected by double contrast films. PMID- 8220028 TI - Pancreatic plasmacytomas in a patient with multiple myeloma: CT and ultrasound findings. AB - Extramedullary plasmacytomas are an unusual manifestation of multiple myeloma. They occur most frequently in tissues or organs rich in reticulo-endothelial cells. Pancreatic plasmacytomas are rare, with only a few case reports in the literature. We present the ultrasound (US) and computed tomographic (CT) findings of two pancreatic plasmacytomas in a patient with multiple myeloma. PMID- 8220029 TI - The evaluation of gallbladder function by quantitative radionuclide cholescintigraphy before and after ESWL for gallstones: preliminary report. AB - We assessed changes of gallbladder function including concentration and contraction in patients with gallstones after extracorporeal shockwave lithotripsy (ESWL). The abilities of concentration and contraction were expressed as filling fraction (FF) at 90 min and ejection fraction (EF) at 30 min after a fatty diet by Tc-99m DISIDA cholescintigraphy. A total of 12 patients who had symptomatic gallstones without cholecystitis were included in our study. ESWL failed in three cases: FF decreased in two of three cases and increased in one of three cases, whereas EF decreased in two of three cases and increased in one of three cases. In another nine cases, ESWL was successful and the gallstones were fragmented. One month after ESWL, in three of these nine cases, the gallstones had completely disappeared. In the three cases at 1 month after ESWL, FF decreased in two of three cases and increased in one of three cases, whereas EF decreased in one of three cases and increased in two of three cases. In the remaining six cases after ESWL, there were still some residual stone fragments in the gallbladder. In these six cases after 6 months, no fragments were found in the gallbladders, the third Tc-99m DISIDA cholescintigraphy was performed. In these six cases, the changes of FF and EF, before ESWL, 1 month after ESWL, and 6 months after ESWL, were irregular and fluctuant. However, no significant improvement of gallbladder function was demonstrated even when ESWL was successful.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8220030 TI - Budd-Chiari syndrome: imaging with pathologic correlation. AB - We retrospectively evaluated 21 patients with Budd-Chiari syndrome who underwent liver transplant. The pathological findings were correlated with imaging studies that included computed tomography (CT) in all cases, sonography in 20, and magnetic resonance (MR) in 15. Pathological features of Budd-Chiari syndrome in subacute or chronic form, such as parenchymal fibrosis, hemorrhage, and congestion, were found in all resected livers. These occurred usually in conjunction with restricted hepatic veins due to thrombosis or fibrosis with partially recanalized lumen. The status of hepatic veins was correctly assessed and correlated with pathology in 13 of 20 patients who had sonograms, in 12 of 15 patients who had MR, and in nine of 18 patients with contrast-enhanced CT scans. Patency of the inferior vena cava was well seen by all three modalities; parenchymal abnormalities were best visible on CT (19 of 21), while ascites, caudate lobe enlargement and collateral vessels were best detected with MR or CT. We conclude that each imaging modality offers certain values and limitations in the assessment of vascular or parenchymal findings in Budd-Chiari syndrome. PMID- 8220031 TI - Hepatic bacillary angiomatosis in a patient with AIDS. AB - We report a case of bacillary angiomatosis involving the liver in addition to multiple cutaneous sites in a patient with AIDS. Abdominal CT demonstrated multiple, small low-attenuation lesions throughout the hepatic parenchyma. Consideration of this entity in the proper clinical setting is essential since it is a readily treatable infection. PMID- 8220032 TI - Hodgkin's and non-Hodgkin's hepatic lymphoma: sonographic findings. AB - The sonographic studies of 72 patients with pathologically proven Hodgkin's or non-Hodgkin's hepatic lymphoma were retrospectively reviewed. Sixty-eight patients (94%) had secondary hepatic lymphoma (nine of them had AIDS-related lymphoma) and four patients (6%) had primary lymphoma of the liver. Forty-six of 72 patients (64%) had diffuse hepatic involvement, and 26 of 72 patients (36%) had focal liver lesions as demonstrated by sonography. Four patterns of disease were identified: (a) hepatomegaly was depicted by sonography in 26 of the 59 patients with secondary hepatic lymphoma not related to AIDS, in two of the nine patients with AIDS-related secondary hepatic lymphoma, and in one of the four patients with primary hepatic lymphoma; (b) multiple rounded well-delineated hypoechoic liver lesions were found in 22 of the 68 patients with secondary hepatic lymphoma; (c) a large heterogeneous echoic mass, which was an evocating clue to the diagnosis of primary lymphoma of the liver, was found in the four patients with primary lymphoma of the liver; and (d) an absence of sonographic abnormalities was found in 20 of the 59 patients with secondary lymphoma not related to AIDS. Liver involvement with lymphoma should be considered in any patient who develops multiple homogeneous hypoechoic liver masses, even in the absence of known underlying lymphomatous disease. PMID- 8220033 TI - Occult hepatocellular carcinoma in cirrhosis: value of ultrasound-guided biopsy of portal vein system thrombus. AB - We report two cases of occult hepatocellular carcinoma associated with alcoholic cirrhosis, in which the diagnosis of malignancy was respectively established by ultrasound-guided biopsy of umbilical vein and portal vein branch thrombus. When measurement of serum alpha-foetoprotein, and liver ultrasonography and/or computed tomography failed to clearly demonstrate hepatocellular carcinoma, the presence of a thrombosis of the portal vein system is highly suggestive of malignancy, which may be easily confirmed by venous biopsy. PMID- 8220034 TI - Sclerosing hepatocellular carcinoma: radiologic findings. AB - The radiologic findings of seven patients with sclerosing hepatocellular carcinoma (HCC), an unusual subtype of HCC, were evaluated. Computed tomography (CT) demonstrated a hypointense mass with marked delayed contrast enhancement. Although the tumor was well-defined, the tumor capsule was not seen. Focal atrophy was seen in four patients. Ultrasound (US) showed an isoechoic to hyperechoic mass without a rim. Angiography revealed prominent tumor vessels and prolonged stains in all cases. Arterial encasement was seen in four patients. On magnetic resonance (MR) imaging, all tumors were hypointense on T1-weighted images and hyperintense on T2-weighted images. On dynamic MR study, remarkable contrast enhancement, which continued to the delayed phase, seemed to be characteristic for sclerosing HCC. In the presence of liver tumors with homogeneous architecture, hypervascularity, prolonged enhancement, absence of tumor capsule, and focal atrophy in high-risk patients of HCC, sclerosing HCC should be considered. PMID- 8220035 TI - Liver parenchymal changes after transcatheter arterial embolization therapy for hepatoma: CT evaluation. AB - We retrospectively reviewed computed tomographic (CT) findings of 118 patients with hepatoma who received sequential follow-up CT after transcatheter arterial embolization (TAE). Thirty-five patients received TAE using Gelfoam particles with cisplatin, 37 patients using Gelfoam particles and iodized oil (Lipiodol) with cisplatin, and 46 patients using iodized oil with cisplatin. Liver atrophy was observed in 33 patients, lobarly or focally, depending on the embolized area. It was frequently associated with portal vein occlusion by the tumor, usage of iodized oil, and repeated embolization therapy. The lobar atrophy was seen in patients who had portal vein occlusion and/or received repeated embolization therapy. The focal atrophy was observed in patients who were administered iodized oil. Infarction developed in four patients who had a thrombus in the portal vein and received peripheral embolization therapy using iodized oil. We conclude that liver parenchymal changes occur frequently in patients who have portal vein occlusion and/or receive peripheral embolization using iodized oil. PMID- 8220036 TI - Fatal liver necrosis following percutaneous ethanol injection for hepatocellular carcinoma. AB - A 76-year-old man underwent an injection of 5 ml of ethanol for the treatment of a hepatocellular carcinoma 3 cm in diameter. Shortly after the procedure, he had an attack of abdominal pain. His condition soon deteriorated and he died 5 days later. Massive hepatic necroses distant from the injection site and a myocardial infarction were found at autopsy. To our knowledge, this is the first fatality associated with percutaneous ethanol injection therapy. PMID- 8220037 TI - High-resolution sonographic guidance for transjugular liver biopsy. AB - A prospective randomized study was performed to compare conventional right internal jugular vein catheterization technique with high-resolution sonographically guided catheterization for transjugular liver biopsy. Forty-seven patients were assigned to undergo either conventional or high-resolution sonographically guided right internal jugular vein catheterization for transjugular liver biopsy. Sonographic guidance was significantly better than conventional guidance, reducing the number of failed catheterizations, from 22% (5 of 23) to 0% (0 of 24) (p < .05). Sonography also reduced the mean number (+/- SD) of passes required to catheterize the vein from 4.21 +/- 1.53 to 1.54 +/- 0.66 (p < .001) and was successful in 100% (5 of 5) of patients in whom conventional catheterization failed. High-resolution sonographic guidance is strongly recommended for transjugular liver biopsy in patients at high risk for bleeding. PMID- 8220038 TI - Inflammatory fibroid polyp of the ileum. AB - We report a patient who presented with recurrent right upper quadrant colics after a previous cholecystectomy. Radiological examination revealed the presence of a polypoid mass in the ileum caused by an anatomo-pathologically proven inflammatory fibroid polyp (IFP) in the ileum. Clinical and pathological aspects related to this rare benign lesion are discussed. PMID- 8220039 TI - Pseudotumoral appearance of small bowel strictureplasty for Crohn's disease. AB - In two patients with Crohn's disease, strictureplasties had been marked operatively by a metal clip, so that definitive location on subsequent small bowel examination was possible. Each strictureplasty presented radiologically as a short annular constriction with apparently shouldered edges and parallel lumen. Similar radiological features were found in five other patients with strictureplasties, suggesting that a pseudotumoral appearance is characteristic of strictureplasty. Attention is drawn to this finding to avoid confusion with malignancy. PMID- 8220040 TI - Metachronous colonic lymphomas complicating chronic ulcerative colitis. AB - The gastrointestinal tract is the most common extranodal site of primary non Hodgkin's lymphoma. Of these, 10-15% occur in the large bowel. Colonic lymphoma is a recognized complication of inflammatory bowel disease, particularly ulcerative colitis and, less commonly, Crohn's disease. We describe a unique case of two metachronous primary lymphomas of the large bowel in a patient with chronic ulcerative colitis. PMID- 8220041 TI - MR imaging of ulcerative colitis. AB - High-resolution magnetic resonance imaging (MRI) was used to study 16 resected rectosigmoid specimens of patients treated with total colectomy for severe ulcerative colitis (UC). Six normal colon specimens were also studied as a control group. Moreover, a parallel study of the pelvis of 24 patients with a proven diagnosis of UC was performed with the same MR system. Both in vitro and in vivo MRI findings [thickening and signal intensity (SI)] of the mural layers were qualitatively evaluated by two radiologists and compared with gross and microscopic aspects. In vitro results showed that MRI was able to identify all layers of the colonic wall. In particular in UC specimens, MRI identified thickening and the peculiar abnormal hyperintensity of the mucosal and submucosal layers on spin-echo (SE) T1-weighted images. In vivo results confirmed the high signal intensity of the mucosal and submucosal layers. These findings were not observed in the control group in which the superficial layers appeared low in intensity on SE T1 images. Our preliminary experience suggests that MRI should be considered a new imaging modality for detecting UC colonic wall changes. PMID- 8220042 TI - Primary lymphoma of the colon and rectum: CT and barium enema correlation. AB - This paper presents the computed tomographic (CT) and barium enema (BE) findings in seven patients with proven primary lymphoma of the colon and rectum. CT and BE examination are complimentary studies in the evaluation of primary lymphoma of the colorectum, and certain relevant findings may be missed when radiographic evaluation does not include both modalities. Both CT and barium studies are very accurate in detecting bulky endoexoenteric tumor masses, although CT may suggest features which can differentiate primary lymphoma from adenocarcinoma. The renal utility of obtaining both a CT and BE examination may lie more in diagnosing complications, such as fistula formation and in the evaluation of subtle infiltrative lesions. While CT is necessary for staging purposes, BE examination may be invaluable for detecting subtle mucosal filling defects which could be missed on CT. PMID- 8220043 TI - Rectal carcinoma: preoperative staging and detection of postoperative local recurrence with transrectal and transvaginal ultrasound. AB - Transrectal ultrasound (TRUS) was performed preoperatively in 35 patients with rectal carcinoma and the results were compared to histologic findings. In the same group, postoperative studies were performed in 22 patients; in women, transvaginal ultrasound (TVUS) was added to the transrectal study. According to Duke's classification modified by Astler-Coller, in relation to the "T" parameter, TRUS correctly staged 33 of 35 neoplasms (accuracy, 94.3%); one was overstaged and one was understaged. In detection of lymph node involvement, accuracy was 74% (sensitivity 69%, specificity 73.9%). Recurrent local tumors, histologically confirmed, developed in two of 22 postoperative patients who had undergone curative anterior resection. This study demonstrates that TRUS is an accurate method in preoperative staging of rectal carcinoma. In the prospective study, the role of follow-up TRUS and TVUS in detection of local recurrences is evaluated. PMID- 8220044 TI - Main renal vein invasion by a transitional cell carcinoma of the renal pelvis: documentation with CT. AB - Invasion of the main renal vein by transitional cell cancer of the renal pelvis is an infrequently reported event. No accurate clinical frequency of this phenomenon is available. Extensive invasion of the renal parenchyma by the tumor usually is present by the time it presents in the renal vein. This article represents but the second documenting main renal vein involvement depicted with computerized tomography in a patient with carcinoma of the renal pelvis. PMID- 8220045 TI - Radiographic appearance of the pars nuda urethrae in the voiding urethrogram. AB - The pars nuda is the most anterior segment of the male membranous urethra, extending from the urogenital diaphragm to the urethral bulb. It differs from adjacent urethral segments in being incompletely supported by corpus cavernosum and musculature. Usually, this part of the urethra is difficult to distinguish in a voiding urethrogram. Occasionally, however, it may stand out clearly in certain phases of urethral muscular activity, resulting in a roentgen picture which may mimic an abnormality. PMID- 8220046 TI - Congenital anterior urethral diverticulum. AB - A congenital anterior urethral diverticulum is a rare abnormality. We present two adults with nonobstructing congenital wide-mouthed diverticulum and an adult with a diverticulum containing a partially obstructing distal lip. The clinical presentation, radiographic appearance, treatment, and possible etiology are described. PMID- 8220047 TI - Adult prostatic sarcoma. AB - A 57-year-old male with a high grade leiomyosarcoma of the prostate is presented. The local extent of the tumor was accurately described by magnetic resonance imaging (MRI). Following chemotherapy, the tumor volume was reduced by 60% and was judged to be clinically resectable by MRI. Despite radical cystoprostatectomy, the patient died of metastatic disease. PMID- 8220048 TI - Uterine myolipoma: CT and US. PMID- 8220049 TI - [Brain death and thanatology]. AB - New technologies in medicine dramatically open a twilight-zone of ignorance between life and death. The argument shows that the present definition of brain death as the death of a human person is a convention with a specific philosophy behind. You will meet the problem with more accuracy when referring to an ethics of intransparence that allows an individual decision with respect to certain qualified conditions. Only from this starting-point the informed ex ante consent for an organ donation seems to become the only conclusive but at the same time justified decision. PMID- 8220050 TI - [Theological-ethical theses of organ transplantation]. AB - The message of the resurrection from the dead is meant to human beings living and dying in the unity of body and soul. The personality of man is unseparably connected with this unity--even beyond the death. The brain death only marks a (decisive) point during the process of dying, but the brain death cannot be defined as the death of a human being (in general). Theological ethics object to this definition and to a new dualism of brain and body as well as of body and personality (resp. soul), because this dualism socializes the organs of individuals and denies the personal dignity of disappearing life. Therefore the explantation of organs must depend on a personal declaration of consent given by the adult sponsor himself. And each information given on organ transplants must clarify that the explantation of organs means an interruption of dying. PMID- 8220051 TI - [Brief definitions of medical ethics concepts. 29. Brain death and informed consent. The planned organ transplantation law in Germany]. PMID- 8220053 TI - The new temperance movement in the United States: what happened to macrostructural factors in alcohol problems? PMID- 8220052 TI - Hair analysis for drugs: technological break-through or ethical quagmire? PMID- 8220054 TI - Population and high-risk approaches both necessary to reduce alcohol harm. PMID- 8220055 TI - What are the rules of thumb for avoiding problem drug use? PMID- 8220056 TI - Trends in the development of alcohol and drug treatment services in Ontario: a replication and extension of a previous study. AB - This paper summarizes the major trends in the development of alcohol and drug treatment services in Ontario from 1979 to 1989. Data were obtained from all treatment services in the province by surveys undertaken in 1980, 1983, 1986 and 1989. Supplementary archival data are included on the use of American treatment programs by Ontario residents over a similar time period. Across the period of analysis, there has been a rapid increase in the number of alcohol and drug programs (130 to 217), their total cost ($44.4 million to $77.1 million) and the total treatment caseload (30,356 to 61,622). With respect to different types of services, the largest growth in capacity has occurred for specialized assessment/referral centres. Use of short-term residential resources within the province has risen slightly but this has been augmented by a rapid increase in the use of similar programs in the United States. Contrary to expectations from research evidence and provincial policy initiatives, only modest gains have been experienced with non-residential treatment alternatives compared to the increases in availability and utilization of residential treatment programs. PMID- 8220057 TI - Recent liver cirrhosis declines: estimates of the impact of alcohol abuse treatment and alcoholics anonymous. AB - This paper examines the proposition that increased treatment for alcohol abuse and Alcoholics Anonymous (AA) membership can account for a large part of the recent declines in cirrhosis mortality and morbidity. Data on treatment and AA membership in the USA between 1979 and 1987 and in Ontario between 1975 and 1986 are used, together with estimates of cirrhosis risk and the likely impact of treatment and AA membership. The results show that increased treatment levels and AA membership could account for all of the reductions in cirrhosis deaths and hospital admissions in Ontario. In the USA all of the deaths and about 40% of the admissions could be accounted for by these factors. PMID- 8220059 TI - Problem drinking and high-risk driving: an analysis of official and self-reported drinking-driving in New York State. AB - The authors collected data from 878 respondents at high risk of problem drinking and drunk driving and tested a hypothesis that stipulates problem drinking and high-risk driving as two necessary conditions of drunk driving. Controlling for a number of alcohol and non-alcohol-related variables, the analysis shows problem drinking to have consistent and significant effects on repeat DWI offenses and on the frequency of self-reported drinking-driving events. High-risk driving increases the frequency of self-reported drinking-driving. Males are more likely than females to be arrested for DWI, but there is no gender differences in self reported drinking-driving. The authors further note a possible 'suppress effect' in that a negative relationship between DWI arrests and high-risk driving is concealed by problem drinking. That is, problem drinkers with multiple DWI arrest records may drive more carefully than before so as to avoid further contact with the police and licensing authorities. Public policy implications of the findings are discussed. PMID- 8220058 TI - Effects of a saliva test pipeline procedure on adolescent self-reported alcohol use. AB - Self-reports on alcohol use collected via school-based questionnaires, telephone surveys, and household interviews are central measures in many studies in the alcohol field. The validity of such self-reports remains an issue. Use of biological pipeline procedures is one way in which the quality of self-reports might be improved. The current study tested the effectiveness of a saliva test pipeline procedure in increasing drinking disclosure rates among adolescents in the sixth and eighth grades. Two sixth-grade classes from each of 14 elementary schools (n = 828) and four eighth-grade classes from each of 8 middle schools (n = 754) were selected. Half of the classes in each school were assigned to the pipeline condition and half to the control condition. Each student in the pipeline condition was asked to provide a saliva sample via dental roll before completing a questionnaire that all students (pipeline and control) received. Pipeline students were told that "some of the saliva we collect today will be tested in a laboratory and will provide a biological measure of alcohol use." Sixth- and eighth-grade students exposed to the alcohol procedure reported 5 to 7% higher alcohol use prevalences than students in the control group. While the pattern of improved reporting under the pipeline condition held across four alcohol-use measures and two grade levels, the effect was statistically significant for only one measure. The pipeline procedures used here had small effects on adolescent self-reported alcohol use. PMID- 8220060 TI - A theory-driven approach to the evaluation of professional training in alcohol abuse. AB - This paper begins by observing that, to date, evaluations of brief training courses in alcohol abuse for non-specialist professionals indicate that they have little influence on attitudes and behaviour. The reasons why this is so have not been studied in detail, and such training courses continue to be widely used despite their minimal effects. It is argued that the failure of this field of inquiry to develop beyond this point is due to the fact that, with only a very few exceptions, it has not been informed by theoretical concerns. The research in this area is discussed in terms of the types of models tested and the research designs typically used in evaluations. This is followed by a detailed description of the 'theory driven approach' to evaluation. It is proposed that the use of such an approach by those concerned with the development and evaluation of training in alcohol abuse for non-specialists would increase the likelihood of identifying the real effects of such programmes and the processes that mediate their successful implementation. This would result in a more purposeful use of educators' and evaluators' energies and skills. PMID- 8220061 TI - Structural changes in the hippocampal formation after long-term alcohol consumption and withdrawal in the rat. AB - The effects of long-term alcohol consumption and withdrawal upon the structure of the rat hippocampal formation were studied by applying morphometric methods to material processed for light and electron microscopy. The somatostatinergic neurons of the hilus were also studied. Groups of 6 rats were treated as follows: (a) given alcohol for 6, 12 and 18 months; (b) paired controls; and (c) rats switched to a normal diet in the 6 months after 6 and 12 months of alcohol intake. A progressive loss of hippocampal neurons after chronic alcohol consumption was found. The loss was aggravated during withdrawal from alcohol, with the exception of the hilar cells. The dendrites of granule cells from the alcohol-treated rats displayed signs of regrowing, but they did not do so in rats withdrawn from alcohol. The synapses between mossy fibre terminals and CA3 dendrites appear to be rather resistant to alcohol insult, and evidence of morphological plasticity was found in withdrawn rats. If an homology can be established between humans and rodents then the changes observed in alcohol-fed rats can be regarded as underpinning some of the functional and behavioural alterations depicted under these circumstances. The peculiar changes found in some nerve cell populations after withdrawal of alcohol could be related to the deficient or incomplete functional recovery often seen after abstinence from alcohol. PMID- 8220062 TI - A comparison of doctors' practice in notifying addicts to the Home Office and reporting them to the North Western Drug Misuse Database. AB - Doctors have been required to notify named addict patients to the Chief Medical Officer at the Home Office since 1968, and since 1990 have been encouraged to report voluntarily all their drug misusing patients to anonymized NHS regional databases. The North Western Drug Misuse Database, set-up for research purposes in 1985, was the forerunner of these databases. Compliance by doctors from three North Western District Health Authorities with both data collection systems between 1986 and 1989 was assessed by matching the names of notified addicts with the attributors of individuals reported to the NWDMD as users of notifiable drugs. By 1989 72% of addicts notified were also reported to the NWDMD although doctors working in hospital general departments still tended only to notify them. There was no evidence that particular general practitioners consistently did not notify their addict patients while reporting them to the NWDMD. The findings suggest that it will take some time for doctors to become accustomed to reporting all their drug misusing patients to the regional databases as well as notifying to Home Office those who met the notification criteria. PMID- 8220063 TI - The effects of methadone on immune function among injecting drug users: a review. AB - Methadone maintenance therapy is advocated as a major preventive strategy for the spread of the human immunodeficiency virus (HIV) and other blood-borne infectious agents among injecting drug users (IDUs) because of its effects in decreasing the frequency of injecting and presumably sharing of equipment. As an opioid agonist, methadone may share the direct and indirect immunoregulatory effects of other opioids, and thus affect susceptibility to, and the natural history of, HIV infection. Available evidence pertaining to methadone and immune function is reviewed. The long-term immunosuppression observed in heroin injectors on present (incomplete) evidence appears to be caused by factors associated with a drug using lifestyle rather than by a direct action of heroin. Although data are conflicting, it is most likely that methadone does not significantly impair immune function and is safe for HIV-infected IDUs, possibly even allowing some improvement of immune function to occur. The increasing reliance placed on methadone maintenance to control the epidemic of HIV infection in IDUs requires that remaining uncertainties regarding methadone and immune function are clarified urgently. PMID- 8220064 TI - A longitudinal study of reasons for smoking in adolescence. AB - This longitudinal study examined factors related to smoking at age 13 and to persistence of smoking from ages 13 to 15 years in a sample (n = 719) of New Zealand adolescents. History of smoking at 9 and 11 years predicted smoking at 13 (odds ratio = 2.8), persistence of smoking from age 13 to 15 (OR = 2.4) and smoking at 15 among those not smoking at age 13 (OR = 2.4). While there were no significant sex differences in pre-adolescent and early adolescent smoking, by age 15 more girls than boys reported smoking. A concern with the immediate negative effects of smoking (taste, smell, feeling ill and feeling silly) as a reason for not smoking at age 13 was inversely related to smoking at age 15 (OR = 0.4). Reasons for smoking at age 13 were not associated with later smoking. Family disadvantage and use of alcohol and other drugs were also associated with later adolescent smoking. PMID- 8220065 TI - Stability and prevalence of drinking among young adults. AB - This data note draws upon the National Longitudinal Survey (NLS) of Labor Market Experience in Youth beginning at ages 17-24 to describe the stability and prevalence of alcohol use over a 6-year period up to ages 23-30. Approximately 70% of men and 58% of women maintained their drinking status throughout the study. The onset of current and heavier drinking decreased with increasing age while the offset of current and heavier drinking increased with increasing age. The absence of current drinking was unrelated to age for both men and women as was the presence of heavier drinking among men. PMID- 8220066 TI - Comments on editorial 'Tobacco advertising bans cut smoking'. PMID- 8220067 TI - Localization of myosin in normal human liver hepatocytes using immunohistochemical amplification methods. AB - Different immunohistochemical amplification systems were used to visualise myosin in normal human hepatocytes. With biotin-streptavidin-peroxidase and immunogold silver staining, myosin was distributed along the plasma membranes and at the bile canaliculi. With biotin-streptavidin-rhodamine, myosin was mainly found at the bile canaliculi level, however with confocal microscopy, the plasma membrane fluorescent staining was more apparent. The staining pattern of myosin appeared to be similar to that of actin in normal human hepatocytes. PMID- 8220068 TI - 1H and 23Na NMR relaxation times study of pectin solutions and gels. AB - 1H and 23Na longitudinal and transverse relaxation times have been measured to examine the concentration dependence of the dynamic behaviour of pectin solutions and gels. T1 and T2 relaxation times were measured in HDE pectin solutions and gels prepared with different cosolutes. A lowering of T1 and T2 values was observed in relation to a better efficiency of the intermolecular forces between polymer molecules and/or the formation of more extended junction zones. The T1/T2 ratio was also exploited indicating that even bulk water experiences anisotropic motions due to the gel formation. A correspondence of NMR results with previous reported data of rheological measurements of pectin gels prepared with the same cosolutes was found. PMID- 8220069 TI - Effect of sodium butyrate on the expression of retinoblastoma (RB1) and P53 gene and phosphorylation of retinoblastoma protein in human colon tumor cell line HT29. AB - Sodium butyrate is known to induce morphological and biochemical changes associated with cell differentiation in some colon tumor cell lines including HT29. In our present study we observed that sodium butyrate treatment caused a decrease in the level of expression of RB1 gene on day seven of butyrate treatment but a gradual six to sevenfold decrease in the level of expression of p53 gene. Western blot analysis revealed a decrease in the level of the phosphorylated form of Rb protein (pRb) and an increase in the level of underphosphorylated pRb as compared to the control cells. These changes in the phosphorylation level were observed from day three of sodium butyrate treatment. In addition, the flat foci forming large differentiated cells also began to appear after 3 days of sodium butyrate treatment. In this study, we are able to show that, besides induction of differentiation, sodium butyrate treatment can also cause a reversal in the phosphorylation status of the pRb in colon tumor cell line HT29. These results suggest that the phosphorylation level of pRb could be associated with the cell differentiation process in human colonic epithelium and as a consequence in its neoplastic development. PMID- 8220070 TI - Autoradiographic demonstration of the distribution of diacylglycerol in the gastric muscularis muscle of Bufo marinus: is diacylglycerol one of the second messengers in the muscularis muscle? AB - The distribution of 1,2-diacylglycerol (DAG) in the muscularis muscle of Bufo marinus has been determined using autoradiographic techniques. Strips of the muscle from the body of the stomach were fixed in 4% paraformaldehyde/2.5% glutaraldehyde, postfixed, washed and longitudinal sections (15 microns) were cut on a cryotome and placed on gelatinized slides. The sections were then incubated in the presence and absence of agonist, acetylcholine (ACh) 10(-5) M or carbachol (CCh) 10(-5) M plus Li+ (10 mM) in the medium which causes a marked potentiation of agonist-stimulated formation of cytidine diphosphate-DAG (CDP-DAG). The sections were processed through an autoradiographic technique using [3H] cytidine, which binds to 1,2-diacylglycerol within the tissue to form CDP-DAG. Analysis of the developed tissue slides indicated that the dose of ACh (10(-5) M) which had been predetermined to elicit automaticity of the preparation in vitro increased the density of CDP-DAG grains. When the muscle strips were pretreated with ACh (10(-5) M) and CCh (10(-5) M) in the presence of LiCl (10 mM), the density of the CDP-DAG grains were further enhanced. CDP-DAG grains were localized throughout the muscle fibers. The increase in the density of the grains which was induced by the conditions eliciting automaticity suggest that DAG is one of the second messengers in the manifestation of automaticity of the muscularis muscle of Bufo marinus. PMID- 8220071 TI - A quantitative analysis of modulations occurring in cellular c-myc protein content, %S phase and growth balance under growth-inhibitory conditions. AB - The c-myc protein was one of the first proto-oncogene products to be linked to the increased proliferative activity of neoplastic cells. However, few studies have attempted to quantify changes occurring in cellular c-myc protein content in response to growth-inhibitory conditions, or to relate such changes to total cellular protein (TCP) levels, %S phase cells and/or cellular growth balance. Knowledge of such relationships is important for determining the biological relevance of the c-myc protein as a marker for proliferating cells. In this study, a dual-laser flow cytometric technique employing three fluorescent dyes was used to quantify cellular changes in c-myc protein, TCP, DNA and growth balance in exponentially-growing and serum deprived U118MG, A-172 and HL-60 cells. Results obtained by flow cytometry were verified using other techniques. Changes in c-myc protein content were found to occur independently of changes in TCP, %S phase or cellular growth balance, and varied between cell lines. These results indicate that cellular c-myc protein determinations convey information that is unique from other indicators of cellular growth and proliferation. Such information may be linked, however, to the nutritional status and origin of the cells being assayed. PMID- 8220072 TI - Mercury, zinc and selenium bioaccumulation in tissues and organs of Mediterranean striped dolphins Stenella coeruleoalba meyen. Toxicological result of their interaction. AB - Neutron activation analysis of 13 Mediterranean striped dolphins Stenella coeruleoalba showed high mercury and selenium contaminations of main tissues and organs of these cetaceans. The mercuric contents were excessive, particularly in liver (from 68 to 2272 micrograms/g dry wt. basis), then in kidney, lung, muscle, heart and brain. The selenium concentrations were also high in liver (from 45 to 1320 micrograms/g dry wt. basis), then in kidney, lung, muscle, skin and heart. The main way of contamination seems to be the food through trophic network, but skin and lung are also able to play a part which must be elucidated. The average Hg/Se ratios in liver and kidney were respectively 1.82 and 1.59. Linear relationship between mercury and selenium concentrations in tissues and organs, particularly in liver and kidney, were confirmed. The mercury and selenium interaction on a toxicological point of view was established by a statistical approach; in the same way, intervention of zinc, metallothioneins and glutathiones have been discussed. PMID- 8220073 TI - Reoxygenation injury of rat hepatocytes: evaluation of nucleotide depletion and oxidative stress as causal components. AB - Isolated rat hepatocytes were used for the evaluation of nucleotide depletion and oxidative stress as two causal components of postischemic injury following oxygen deficiency. The ATP and GTP loss during anoxia was accompanied by temporary increases of nucleotide degradation products. The critical duration of anoxia for a complete ATP restoration during reoxygenation was between 30 and 60 min. The oxidative stress during reoxygenation was demonstrated by decrease of GSH concentration and increase of TBA-RS level. The tremendous GSH loss could not be balanced by the slight GSSG increase during reoxygenation. Prevention of GSH decrease and TBA-RS increase in parallel to prevention of viability loss in presence of oxipurinol in contrast to lacking improvement of ATP and GTP restoration by this drug speak in favor for the oxidative stress as major causal component for postischemic injury of hepatocytes in comparison with depletion of energy-rich purine nucleotides. The inhibition of formation of reactive oxygen species via xanthine oxidase reactions was found to be the dominant protective effect of oxipurinol against postischemic injury of hepatocytes in comparison with lacking influence on nucleotide salvage and ATP/GTP regeneration and with radical scavenging. PMID- 8220075 TI - A new approach to collagen fiber orientation in cow skin by the microwave method. AB - The fiber orientation of cow leather sheets corresponding to the corium of the middle layer in the cow skin was studied by measuring the angular dependence of transmitted microwave intensity and the complex dielectric constant at a microwave frequency of 3.9 GHz. The direction of the minimum transmitted microwave intensity and the maximum dielectric loss agrees with that of the maximum mechanical breaking strength, suggesting that the collagen fibers constituting the cow leather should be preferably oriented in the direction of minimum transmitted microwaves and the maximum dielectric loss. The electron microphotograph supported this suggestion. The main chain direction of collagen fibers and the degree of orientation varied from position to position in the sheet. The present microwave method is convenient for quick determination of the orientation of collagen fibers in the cow skin. It can be applied non destructively and contact-freely. PMID- 8220074 TI - Lectin histochemistry of cell-surface glycoconjugates in the primary olfactory projections of the newt. AB - The binding of 14 lectins were performed on paraffin-embedded sections of the olfactory bulb of Triturus to identify specific glycoconjugates on the cell surface of primary olfactory projections. The histochemical lectin staining patterns indicate that the membrane of olfactory neurons terminating in the main olfactory bulb contained prevalently oligosaccharides with alpha-acetyl-D galactosamine as terminal residues. In the accessory olfactory bulb, instead, the primary olfactory projections possess a high density of alpha-D-galactose as sugar residues. The selective lectin binding on the surface of primary olfactory axons suggests that specific cell surface glycoproteins may have a role in the axonal growth due to the continual cycle of proliferation and death of olfactory receptors. PMID- 8220076 TI - L-lysine transport through the basolateral surface of oxyntic glands and plasma membrane of parietal cells isolated from rabbit stomach. AB - L-lysine uptake was measured in isolated oxyntic glands of rabbit stomach in both Na(+)-containing (1.29 +/- 0.29 nmol.mg-1.(20s)-1) and choline-containing (0.93 +/- 0.15 nmol.mg-1.(20s)-1) medium. Time curves and concentration dependence curves showed higher uptake values in the presence of extracellular Na+. The carrier-mediated uptake of L-lysine fit the Michaelis-Menten equation for one saturable component (Kt = 1.42 mM, Jmax = 0.16 nmol.mg-1.s-1) when sodium was replaced by choline in the medium. Two components are apparent when the kinetic analysis was performed in the presence of Na+: component 1 showed lower affinity (Kt = 4.0 mM) than component 2 (Kt = 0.53 mM). The transport constants for the Na(+)-independent component and for the Na(+)-dependent component 2 (i.e. the high affinity component) are in the range described for system y+ in other cells. L-lysine uptake in the choline-containing medium was inhibited only by cationic amino acids and histidine. In the presence of Na+, both cationic and some neutral (His, Cys, Ala, Leu, Phe) amino acids inhibited L-lysine uptake. These overall results and the ratio of Ki obtained for cationic and neutral amino acids suggest that at the basolateral side of the oxyntic glands cationic amino acids transport is mediated by the system y+ and, probably, an ASC like system. The pH insensitivity of L-lysine uptake (in the range 6.5 to 8) supports this hypothesis. Results obtained in isolated parietal cells suggest that L-lysine uptake would be primarily mediated by a transporter which resembles the selectivity of system b(o),+. PMID- 8220077 TI - Alanine as a lipogenic precursor in isolated hepatocytes from obese Zucker rats. AB - Isolated hepatocytes from obese Zucker rats showed an increased capacity for lipid synthesis measured as the incorporation of 3H2O into lipid fractions. In addition lipid synthesis from 1 mM U-14C-alanine was elevated as compared to those isolated from their lean counterparts. On these lines, the amino acid was a better lipogenic substrate than U-14C-lactate at 5 mM concentration. Insulin increased lipid synthesis from the amino acid in the lean animals while showed no effects on this parameter in the obese. While the hepatocytes from the lean animals used to a similar extent U-14C-alanine carbon from 14CO2 production, lipid synthesis and 14C-glycogen incorporation, those from the obese animals showed a decreased oxidation and glycogen incorporation while an augmented lipid synthesis. The total amount of the amino acid taken up by the obese animals was also significantly elevated. Conversely, the metabolic fate of U-14C-leucine was very similar between the two groups. It can be concluded that in the obese Zucker rat alanine is a very important amino acid which contributes to sustain the high liver hyperlipogenesis previously described. PMID- 8220078 TI - [The concept of receptor sorption as a basis for the development of nontraditional methods of therapy, prevention and diagnosis in pathological states]. AB - A potential use of receptor sorption for medical purposes is discussed. This type of sorption is based on selective fixation of exo and endogenous chemical substances and viruses by their cellular receptors, which serve as sorbents, "landing grounds" ("chemical traps"). We propose to elaborate non-traditional methods of therapy, prophylaxis and diagnosis of various pathologies. These methods include: "dialysis by receptors", peroral and local use of isolated receptors, blocking of receptors by specific antireceptor antibodies, and analysis of binding properties of the receptors in various pathologies. We propose to carry out "receptor mapping" ("receptor classification") of the human population. This mapping consists in drawing up a "personal receptor map" carrying information about biochemical properties and binding parameters of the person's cellular receptors. The necessity of careful laboratory and clinical approbation of the proposed methods is emphasized. PMID- 8220079 TI - [The toxic action of the "diabetogenic factor" metabolite in the body during the development of insulin-dependent diabetes]. AB - Investigations of "diabetogenic factor" (DgF) (Diploma No. 386, USSR) in the blood of men and animals with insulin-dependent diabetes have been summarized. The nature and properties of the DgF purified preparation have been outlined and its pathophysiological importance characterized. An inhibitor has been found that inactivate DgF when administered to a diseased individual. It was experimentally established that a single transplantation of cultured healthy beta-cells to an animal with diabetes was successful only in the absence of DgF activity. This leads to stable recover of the animal. The data of other authors have also been briefly discussed. PMID- 8220080 TI - [The hyper- and hypoalgesic effects of human and animal blood serum proteins]. AB - The protein fractions precipitated by ammonium sulfate from the bovine, human and Greenland's seal blood sera enhanced the pain sensitivity of mice, rats and rabbits. The proteins fraction of the seal blood serum was divided in six subfractions by ion-exchange chromatography. One of these subfractions clearly showed hyperalgesic properties, while the others had an opposite effect. The collagenase hydrolysate of the same protein fraction had an analgetic activity. The results of this and previous studies suggest the occurrence of one more nociception-regulating protein-peptide system in mammals. PMID- 8220081 TI - [The enzyme systems in natural populations of the housefly Musca domestica highly resistant to organophosphate insecticides]. AB - Two natural population of house flies from the Podol'sk District, Moscow Province have been studied. The both natural populations proved to be highly resistant to organophosphorus insecticides and sensitive to pyrethroids. The activity of esterases and glutathione-S-transferase has been studied, as well as the sensitivity of the enzymes of esterase complex in vitro to TBTP, DDVP and paraoxon, as compared with that of the sensitive strain SRS. Reliable differences have been established in the sensitivity of non-specific esterases to organophosphorus compounds. The esterase spectrum of enzymes from heads and abdomens of house flies has been studied by electrophoresis in PAAG and the zones of esterase activity have been revealed in the presence of two substrates: 2-HA and ATX. Differences in the activity of catecholamine esterase and cholinesterase and inn the sensitivity of cholinesterase from the natural populations to organophosphorus compounds have been established. PMID- 8220082 TI - The National Surgical Adjuvant Breast Project (NSABP) Breast Cancer Prevention Trial revisited. PMID- 8220083 TI - Shedding new light on the etiology of prostate cancer? PMID- 8220084 TI - Reliability of serum prolactin measurements in women. AB - Prolactin, a hormone indispensable for milk secretion, has been shown to enhance the development and growth of mammary tumors in rodents; however, its importance in human breast cancer is uncertain. Serum prolactin levels are known to fluctuate considerably under normal conditions, and lack of precision in the hormone measurements may have contributed to the largely negative findings in humans to date. The purpose of this study was to investigate the reliability of prolactin measurements in women using stored serum from an ongoing prospective study of breast cancer. Separate groups of postmenopausal and premenopausal women who donated multiple blood samples at approximately 1-year intervals were studied. The reliability of a single log prolactin determination, as measured by the intraclass correlation coefficient, was 0.76 for the postmenopausal women (95% confidence interval, 0.66-0.85) and 0.48 for the premenopausal women (95% confidence interval, 0.31-0.62). These findings suggest that a single measurement is sufficient to characterize the serum prolactin level of postmenopausal women for epidemiological research. For premenopausal women, however, multiple samples are desirable. Controlling for phase of the menstrual cycle does not appear to substantially improve the reliability of premenopausal measurements. PMID- 8220085 TI - Human papillomavirus and cervical intraepithelial neoplasia grade III/carcinoma in situ: a case-control study in Spain and Colombia. AB - A case-control study of 525 cases of cervical intraepithelial neoplasia grade III (CIN III) and 512 controls was conducted in Spain and Colombia between 1985 and 1988 to assess the role of human papillomavirus (HPV) in the etiology of CIN III. HPV DNA in cytological scrapes from the cervix was assessed by Virapap and by polymerase chain reaction (PCR) based on the L1 consensus primers. A subsample of 268 specimens was also tested for HPV DNA using Southern hybridization. In Spain, the PCR-based prevalences of HPV DNA were 70.7% among cases and 4.7% among controls. Odds ratio (OR) and 95% confidence interval (numbers in parentheses) for HPV DNA were 56.9 (24.8-130.6). In Columbia HPV DNA was detected by PCR in 63.2% of the cases and in 10.5% of the controls. The OR was 15.5 (8.2-29.4). The estimated fractions of CIN III attributable to HPV were 72.4% in Spain and 60.3% in Colombia. HPV 16 was the predominant viral type and showed the strongest association with CIN III; in Spain the OR was 295.5 (44.8-1946.4) and in Colombia the OR was 27.1 (10.6-69.5). HPV DNA of unknown type was frequent in HPV-positive cases (18.3% in Spain and 38.0% in Colombia) and controls (66.7% in Spain and 47.4% in Colombia). The comparison of results from Virapap and PCR indicated that PCR is the method of choice for epidemiological studies. These data strongly support the hypothesis of the viral origin of CIN III, the common etiology of CIN III and invasive cervical cancer, and the causal nature of the association between HPV and CIN III. PMID- 8220086 TI - Risk factors for cervical intraepithelial neoplasia grade III/carcinoma in situ in Spain and Colombia. AB - A case-control study of 525 histologically confirmed cases of cervical intraepithelial neoplasia grade III and 512 controls was done in Spain and Colombia to assess the role of various risk factors taking into account the effect of human papillomavirus (HPV). The presence of HPV DNA, assessed by a polymerase chain reaction-based method, was the strongest risk factor identified. In Spain the adjusted odds ratio (OR) and 95% confidence interval (CI) (numbers in parentheses) were 56.9 (24.8-130.6) and, in Colombia, were 15.5 (8.2-29.4). In addition to HPV, the multivariate analysis revealed independent effects of early age at first intercourse (in Spain ORa, 4.3; 95% CI, 2.0-9.3 for ages < 17 versus 20+ years and in Colombia ORa, 9.0; 95% CI, 2.6-30.9 for ages < 14 versus 20+ years), and antibodies to Chlamydia trachomatis (in Spain ORa, 2.3; 95% CI, 1.1 4.5; and in Colombia ORa, 1.7; 95% CI, 1.1-2.7). High parity showed a significant effect only in Colombia (ORa, 2.0; 95% CI, 1.0-5.0 for > or = 6 versus 1) while number of partners of the woman and specially of her husband showed a strong effect in Spain only (ORa, 6.9; 95% CI, 3.1-15.3 for partners of the husband > or = 21 versus 1-5). Smoking and use of oral contraceptives did not show significant or consistent associations. Among HPV-DNA positive women early age at first intercourse and high parity increased the risk of cervical intraepithelial neoplasia III but the effect was statistically significant only for the former.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8220087 TI - Cigarette smoking and alcohol consumption by parents of children with acute myeloid leukemia: an analysis within morphological subgroups--a report from the Childrens Cancer Group. AB - Data from a case-control study of childhood acute myeloid leukemia (AML) including 187 matched case-control pairs were examined for evidence of associations between parental cigarette smoking and alcohol consumption and the subsequent development of childhood AML. The cases were stratified by French American-British morphology in order to evaluate potential differences in risk based on this classification system. There was little evidence of any association between cigarette smoking by parents during the index pregnancy and childhood AML. There was some evidence of an increased risk of AML among children who were diagnosed at or before 2 years of age and whose mothers reported consuming alcohol during their pregnancies (odds ratio, 3.00; 95% confidence interval, 1.23 to 8.35). This finding appeared to be especially pronounced for AML with a monocytic component (M4/M5) (odds ratio, 9.00; 95% confidence interval, 1.25 to 394.5), but a cautious interpretation of these data are advised because of the small number of subjects included in this subgroup analysis. Since this is one of the first case-control studies to evaluate specific French-American-British subtypes of AML, these results may be viewed as generating hypotheses. It is suggested that future studies of childhood AML include: (a) a sufficient number of cases to permit an evaluation of the morphological classification of the cases; and (b) additional questions on the alcohol consumption of the mother during the time of her pregnancy with the index child. PMID- 8220088 TI - Markers for cytogenetic damage in smokers: associations with plasma antioxidants and glutathione S-transferase mu. AB - Biomarkers for increased cytogenetic damage in smokers include sister chromatid exchanges (SCE) in peripheral lymphocytes and micronuclei in sputum cells. These markers may reflect increased cancer risk. Increased cancer risk has also been associated with lower blood levels of the antioxidants beta-carotene and vitamin C and with genetic deficiency of the detoxification enzyme glutathione S transferase mu (GST-mu). We therefore evaluated the associations of plasma antioxidants, GST-mu phenotype, and indices for tobacco exposure with SCEs and micronuclei in a group of 156 male cigarette smokers and 38 nonsmokers. As expected, smokers as compared with nonsmokers had higher SCE levels (5.08 versus 4.71 SCE/lymphocyte) and lower levels of plasma beta-carotene (0.31 versus 0.48 mumol/liter) and blood vitamin C (36.6 versus 33.8 mumol/liter). In smokers, SCEs were weakly correlated with plasma cotinine (r = 0.186) but not with plasma antioxidants (all r < 0.04). Micronuclei in smokers were not correlated with either cotinine or antioxidants (all r < 0.14). As reported previously, SCEs were higher (5.24 versus 4.97 SCE/lymphocyte) in GST-mu-deficient smokers than in nondeficient smokers. Micronuclei, however, were similar in both GST-mu phenotypes (4.3 versus 4.9 micronuclei/3000 cells). No correlation was observed between micronuclei and SCEs (r = -0.025). Large random variations in both SCEs and micronuclei make it difficult to interpret the absence of relations unambiguously. The results indicate that SCEs and micronuclei have only limited sensitivity to variations in cigarette smoke exposure. The association between GST-mu and cancer risk may be mediated through increases in certain forms of smoking-induced DNA damage in GST-mu deficiency. PMID- 8220089 TI - Phenobarbital, drug metabolism, and human cancer. AB - To investigate the possible influence of anticonvulsant treatment on cancer risk, a nested case-control study of 104 lung cancers, 18 bladder cancers, and 322 cancer-free controls was conducted. The background for the study was previous observations among 8004 epileptics in Denmark with a significantly high risk for lung cancer and a significantly low risk for bladder cancer. Cigarette smoking appears to explain the lung cancer excess but not the low risk for bladder cancer, another tobacco-related disease. Information was abstracted on 94 and 95% of the cases and controls, respectively. Lung cancer was not associated with any anticonvulsant drug, but bladder cancer was inversely related to use of phenobarbital (PB). The apparent protective effect of PB was further evaluated in a study of rats given 4-aminobiphenyl (ABP), a bladder carcinogen. The levels of 4-aminobiphenyl adducts in hemoglobin and in bladder and liver DNA were significantly lower in rats given PB prior to 4-aminobiphenyl, compared to controls. These studies suggest that PB may induce drug-metabolizing enzymes of the liver that deactivate bladder carcinogens found in cigarette smoke and provide clues to the role of activation and detoxification of carcinogens in humans. PMID- 8220090 TI - Cytogenetic effects of formaldehyde exposure in students of mortuary science. AB - The effect of low-level exposure to formaldehyde on oral, nasal, and lymphoycte biological markers was studied prospectively in a group of 29 mortician students who were about to take a course in embalming. During the 85-day study period, the subjects performed an average of 6.9 embalmings and had average cumulative formaldehyde exposures of 14.8 ppm-h, with an average air concentration of 1.4 ppm during embalming. Since the average time spent embalming was 125 min, formaldehyde exposures calculated as an 8-h time-weighted average were 0.33 ppm on days when embalmings were done, which was less than the Occupational Safety and Health Administration permissible exposure limit of 0.75 ppm. Epithelial cells from the buccal area of the mouth showed a 12-fold increase in micronucleus frequency during the study period, from 0.046 +/- 0.17/1000 cells preexposure to 0.60 +/- 1.27/1000 cells at the end of the course (P < 0.05). Nasal epithelial micronuclei increased 22%, from 0.41 +/- 0.52/1000 cells to 0.50 +/- 0.67/1000 cells (P = 0.26). In blood cells, the frequency of micronucleated lymphocytes increased 28%, from 4.95 +/- 1.72/1000 cells to 6.36 +/- 2.03/1000 cells (P < 0.05), while sister chromatid exchanges decreased 7.5% (P < 0.05). A dose response relationship was observed between cumulative exposure to formaldehyde and increases in buccal micronuclei in the 22 male subjects but not in the 7 female subjects. We conclude that low-level exposure to formaldehyde is associated with cytogenetic changes in epithelial cells of the mouth and in blood lymphocytes. These cytogenetic effects may be useful as markers of biologically effective dose. PMID- 8220091 TI - Helicobacter pylori, pepsinogen, and risk for gastric adenocarcinoma. AB - The objective of this project was to determine the association of Helicobacter pylori infection and serum pepsinogen levels on subsequent risk for gastric adenocarcinoma. This nested case-control study was set in a large health maintenance organization. One hundred thirty-six cases of gastric adenocarcinoma and 136 matched controls without adenocarcinoma from a large cohort that had contributed serum in the 1960's were studied. The presence of IgG against H. pylori had previously been determined by enzyme-linked immunosorbent assay. Serum levels of pepsinogens I and II were ascertained by radioimmunoassay. In a sample of subjects, the presence of antiparietal cell antibodies was determined by immunofluorescent antibody assay (Nichols Laboratory). There were 98 cases of adenocarcinoma of the antrum, body, or fundus (distal cancers) and 30 of the cardia or gastroesophageal junction (proximal cancers). By univariate analysis, H. pylori infection [odds ratio (OR), 3.6; P < 0.001] and serum pepsinogen I < 50 ng/ml (OR = 2.9; P = 0.003) were both associated with development of distal cancer. In multivariate analysis, there was interaction between the two variables; H. pylori in the absence of low pepsinogen I was independently associated with cancer (OR, 2.4; P = 0.04) but low pepsinogen I in the absence of H. pylori infection was not associated with cancer (OR, 0.8; P > 0.5). In combination, however, H. pylori infection and a low pepsinogen I were associated with a marked increase in the risk of developing distal malignancy (OR, 10.0; P = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8220092 TI - Vitamin D and prostate cancer: a prediagnostic study with stored sera. AB - This study evaluates the risk of prostate cancer in relation to serum levels of the major vitamin D metabolites, 25-hydroxyvitamin D (25-D3) and 1,25 dihydroxyvitamin D (1,25-D). Between 1964 and 1971, more than 250,000 serum samples were collected from members of the Kaiser Permanente Medical Care Plan in Oakland and San Francisco and stored for future use. Levels of 25-D and 1,25-D were measured in samples from 90 black and 91 white men diagnosed with prostate cancer before December 31, 1987 and controls individually matched on age, race, and day of serum storage. Mean serum 1,25-D was 1.81 pg/ml lower in cases than in matched controls (P = 0.002). Risk of prostate cancer decreased with higher levels of 1,25-D especially in men with low levels of 25-D. However, mean 25-D was not significantly different in cases and controls. The association of lower 1,25-D with prostate cancer was found in men above the median age of 57 years at serum storage but not younger men and was similar in black and white men. In men > or = 57 years of age, 1,25-D was an important predictor of risk for palpable and anaplastic tumors but not for tumors incidentally discovered during surgery to treat the symptoms of benign prostatic hyperplasia or well differentiated tumors. PMID- 8220093 TI - Determinants of plasma vitamin E in healthy males. AB - Vitamin E or tocopherol, a known antioxidant, may play a role in the etiology of chronic diseases such as cancer and heart disease. This study examined both "internal" (lipids, lipoproteins, and apoproteins) and "external" (dietary components, physical activity, and body mass index) factors which may influence plasma alpha-tocopherol and gamma-tocopherol levels. Analyses were done using dietary questionnaires and plasma obtained from 65 nonsmoking male volunteers aged 30-59 years. Forty-six men did not take any supplements while 19 took supplements containing vitamin E. A positive correlation (r = 0.32; P < 0.01) between vitamin E intake and alpha-tocopherol status [(ratio of plasma alpha- or gamma-tocopherol/(total triglycerides + total cholesterol)] and a negative correlation (r = -0.33; P < 0.007) between intake and gamma-tocopherol status were observed. The main internal factors, or determinants, for plasma alpha tocopherol for nonsupplement users were plasma triglycerides and apoproteins, apoA1 and apoB, but neither lipids nor apoproteins appeared to affect tocopherol levels in supplement users. External determinants of alpha-tocopherol status in nonsupplement users were vitamin E intake, total fat intake, and body mass index, while in supplement users only vitamin E intake was important. Both vitamin E intake and alcohol intake appeared to affect plasma gamma-tocopherol status in a negative manner. PMID- 8220094 TI - Lung cancer, race, and a CYP1A1 genetic polymorphism. AB - The assessment of human cancer risk using molecular epidemiological techniques involves determining the relative contributions of inherited and acquired genetic predispositions, in the context of environmental exposures. Recently described genetic polymorphisms for CYP1A1, a gene involved in the metabolic activation of polycyclic aromatic hydrocarbons, have been associated with lung cancer risk in a Japanese population. We report herein findings from a United States case-control study of lung cancer (56 cases; 48 controls). The polymerase chain reaction followed by an Msp1 restriction enzyme digestion was used to analyze constitutive DNA but no association between the restriction fragment length polymorphism and lung cancer risk was found (odds ratio, 0.7; 95% confidence interval, = 0.3-1.6). Analysis of genotype by cumulative smoking status did not reveal an elevated risk among lesser or greater smokers. The presence of the CYP1A1 Msp1 site-present allele, which was previously found to be associated with Japanese lung cancer risk, was statistically increased in African compared to Caucasian Americans (odds ratio, 2.9; 95% confidence interval, 1.2-2.7). When stratified by race, however, no association between case status and the polymorphism was observed, but the small number of study subjects within each racial group limited the statistical power. Larger studies are required to evaluate the risk of the CYP1A1 Msp1 polymorphism in African Americans. PMID- 8220095 TI - Problems in assessing the relative predictive value of internal markers versus external exposure in chronic disease epidemiology. AB - Epidemiology traditionally has relied on measures of "external" exposure in determining the association between exposure and disease. Recently, there has been increasing reliance on internal markers reflecting internal dose and/or early stages of disease. In the context of observational studies of chronic disease in which there is a known exposure-disease association, the question arises whether the external exposure or the internal marker is a better predictor of eventual disease outcome. Here we describe some simple approaches to evaluate the relative predictive value of the internal marker (or biomarker, defined in the most general sense) versus the exposure, as well as their limitations. The problems of assessing the predictive value of internal markers for chronic disease are illustrated via two examples: (a) carcinogens, cytogenetic outcomes, and cancer; and (b) asbestos, asbestosis, and lung cancer. We conclude that it is unlikely that observational epidemiology will allow a full assessment of the predictive value of cytogenetic outcomes versus exposure for cancer in humans exposed to known carcinogens in the near future, although animal studies could provide important complementary information. For asbestos, data to date indicate that the presence or absence of asbestosis is a better predictor of lung cancer in an exposed population than is the level of exposure to asbestos itself. In general, the most useful markers for predicting chronic disease are ones which persist over time. PMID- 8220097 TI - American Society of Preventive Oncology 17th annual meeting. PMID- 8220096 TI - Toenail trace element levels as biomarkers: reproducibility over a 6-year period. AB - We assessed the reproducibility over a 6-year period of 16 trace elements measured in toenails by comparing levels in paired specimens collected in 1982 1983 and 1988 from 127 women in the United States. The Spearman correlation coefficients for the reproducibility of toenail levels of selenium and arsenic (both known to reflect intake of these elements) were 0.48 and 0.54. Correlations for other elements ranged from 0.26 (copper) to 0.58 (zinc). In utilizing biomarkers to assess exposure in epidemiological studies of cancer and other chronic disease, random within-person variability in exposure leads to attenuation of measures of association between exposure and disease. We demonstrate the effect of such variability on odds ratios from a hypothetical case-control study. For a true odds ratio of 3.0 (for a comparison of the highest quintile versus the remaining 4 quintiles of exposure) the odds ratios which would be observed in the presence of the degree of within-person variability demonstrated in this study were 2.15 for toenail arsenic and 1.67 for toenail copper levels. Toenail concentrations of certain trace elements are useful biomarkers of exposure in which a single sample is assumed to represent long-term exposure. However, substantial attenuation in measures of association may occur. PMID- 8220098 TI - The occurrence of macrophages in the retina and periretinal tissues in ocular diseases. AB - Specimens obtained from eyes with various ocular diseases were examined immunohistochemically using a panel of monoclonal antibodies (Ki-M1P, K1-M4, CD68, anti-lysozyme, and anti-cytokeratins) to establish the occurrence of macrophages in the retina and periretinal tissues and to determine whether they can be distinguished from migrated cells of the retinal pigment epithelium (RPE). Eyes with proliferative diseases and intraocular melanomas were found to contain more macrophages in the retina than those with uveitis and glaucoma. The epiretinal membranes and subretinal space in eyes of the former group often exhibited additional clustered macrophages and migrated RPE cells. In all specimens studied, RPE cells reacted with antibodies KL-1, CK7, CK18, or CK19 but not with the CD68, Ki-M1P, or lysozyme antibodies. Control eyes without any known disease also contained rare macrophages in the retina. In conclusion, macrophages are regular and normal constituents of the retina that can be clearly distinguished immunohistochemically from migrated RPE cells. Their frequency varies depending on the type of ocular disease involved. PMID- 8220099 TI - Permeability of the blood-retinal barrier and the blood-aqueous barrier in type I diabetes without diabetic retinopathy: simultaneous evaluation with fluorophotometry. AB - For the evaluation of a possible malfunction of the blood-retinal barrier (BRB) and the blood-aqueous barrier (BAB) in type I diabetes without manifest angiopathy after i.v. injection of sodium fluorescein, the permeability of the BRB (P) and the permeability coefficient of the BAB [P(a)] were simultaneously determined by fluorophotometry in 34 eyes of 34 type-I diabetics [hemoglobin (Hb)A1c = 6.6% +/- 0.9%] without retinopathy whose age ranged from 19 to 38 years (mean, 30.5 +/- 5 years); the diabetes duration was between 5 and 18 years. Fluorescein angiography was performed to exclude nonperfused areas. In all, 34 eyes of 34 healthy volunteers whose age ranged between 23 and 34 years (mean, 28.5 +/- 3.3 years) served as controls; in this group, fluorophotometry was performed twice to evaluate reproducibility. The mean BAB permeability coefficient in diabetics [P(a) = 5.3 +/- 1.8 x 10(-4)/min] was significantly increased (P = 0.00003) as compared with control values [P(a) = 3.7 +/- 0.7 x 10( 4)/min]; BRB permeability in diabetics (P = 3.2 +/- 1.4 x 10(-7) cm/s) was raised, with this elevation being of lower significance (P = 0.019; controls, P = 2.6 +/- 0.7 x 10(-7) cm/s). We found a decrease in BRB permeability depending on diabetes duration (r = -0.15; P = 0.007) that was not significant in the BAB (r = -0.1; P = 0.24). No correlation was found to exist between permeability and hemoglobin (Hb)A1c values either in the BAB or in the BRB. The reproducibility in controls was 9% in BRB determinations and 12% in BAB measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8220100 TI - Detection and localization of perfluorodecalin in the human eye by fluorine 19 magnetic resonance. AB - Perfluorocarbons are applied as heavy liquids during vitreoretinal surgery. They are removed again intraoperatively because of possible harmful long-term effects. Following vitreoretinal surgery, residual perfluorodecalin (PFD) was detected in four eyes and localized in two others by fluorine 19 magnetic resonance (19F-MR). In vitro analysis of 19F-MR spectra shows that chemical shift artifacts can be avoided much better with PFD than with perfluorotributylamine and perfluoroctane. Therefore, PFD localization by 19F-MR imaging is superior to that of perfluorotributylamine and perfluoroctane. This examination can be performed on currently employed magnetic resonance imaging systems equipped with a fluorine channel. In the event of significant inadvertent residual quantities of PFD and obscured media, 19F-MR may specifically detect and localize PFD. PMID- 8220101 TI - Photodynamic laser therapy of basal-cell carcinoma of the lid. AB - Photodynamic therapy (PDT) remains an experimental approach for the treatment of small, mainly superficial malignant tumors. When given intravenously, hematoporphyrin derivative (HpD) selectively photosensitizes tumor tissue. Activated by light of 630 nm wave-length, HpD leads to tumor necrosis. This paper presents the results of PDT to eyelid basal-cell carcinomas in 21 patients. All lesions primarily responded to the treatment and became necrotic. A generalized photosensitization lasting for more than 4 weeks was seen in all patients. In five patients, lid malformations due to scar formation were noted, being marked in three cases. Ten patients showed a recurrence of tumor after 3-12 months. At present, PDT has no advantage over well-established therapies for basal-cell carcinomas of the eyelid. PMID- 8220102 TI - Antibody-dependent cellular cytotoxicity against cells infected with herpes simplex virus type 1 in Igh-1 disparate congenic mice. AB - The mouse Igh-1 locus on chromosome 12 influences herpetic stromal keratitis (HSK) patterns following corneal challenge with herpes simplex virus type 1 (HSV 1). Both cellular and humoral immune mechanisms appear to be important in modulating responses to HSV-1 infections, but the role of antibody-dependent cellular cytotoxicity (ADCC) is unclear. We studied the effector-cell function and antibody in an ADCC assay in Igh-1-disparate mice. Splenocytes from both HSK susceptible C.AL-20 (Igh-1d) and HSK-resistant C.B-17 (Igh-1b) mice mediated equal amounts of ADCC to HSV-infected cell targets using monoclonal antibodies against HSV-1 glycoprotein D. Natural killer cell activity was significantly greater in C.AL-20 than in C.B-17 splenocytes. IgG2a was less efficient than both IgG1 and IgG2b in mediating ADCC to HSV-1-infected cell targets. The Igh-1 phenotype of the antibody source had no influence on ADCC activity. Our results suggest that the susceptibility of HSK observed in these Igh-1-disparate congenics cannot be explained by qualitative differences in the ADCC activity of effector cells and antibody produced in response to HSV-1 infection. PMID- 8220103 TI - Main sources of infection in 145 cases of epidemic keratoconjunctivitis. AB - Epidemic keratoconjunctivitis (EKC) is a combination of conjunctivitis and keratitis induced by an adenovirus that is found especially in eye clinics and in eye hospitals. In Bavaria, EKC represents a common eye disease and occurs in epidemics in the spring and early autumn. We report on 145 patients who presented with EKC in our hospital between March 17 and September 12, 1991, and who were evaluated prospectively (67 men and 78 women ranging in age from 4 to 85 years). The recent patient history was noted using a standardized protocol to analyze possible sources and pathways of the infection. Overall, 44 of the EKC patients (30%) remembered having undergone eye treatment during the incubation period of 2 weeks before the onset of symptoms. In all, 18 patients (12%) recalled that a family member had also had conjunctivitis during that time, and 4 patients (3%) reported the infection of a workmate during the 2 weeks prior to the onset of symptoms. In 82 patients (55%), no presumed source of infection was apparent. A total of 24 patients (17%) presumably acquired the infection during examination or treatment in our hospital. The main cause was the removal of foreign body, followed by cataract operation. In all, 20 patients (14%) had been treated in private practice during the incubation period; 14 of these remembered having had tonometry, and 4 patients had undergone contact-lens fitting. In 18 patients, virus isolation and serotyping from a conjunctival smear was conducted. In 12 of these patients an adenovirus could be isolated; in all cases it proved to be serotype 8.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8220104 TI - Complete removal of an oculomotor nerve neurinoma without permanent functional deficit. Case report. AB - A case of complete operative removal of a neurinoma of the oculomotor nerve with long-time preservation of oculomotor function despite minor signs of aberrant reinnervation is presented. A review of the literature referring to the clinical appearance, radiological features, treatment, and outcome of 22 cases is given, 18 of which involved operations. To our knowledge, this is the first case to prove that complete operative removal of an oculomotor neurinoma without relevant persisting neurological sequelae is possible. PMID- 8220105 TI - Uncommon chiasmal lesions: demyelinating disease, vasculitis, and cobalamin deficiency. AB - We report on eight patients who presented for evaluation of unexplained visual loss. They all showed a typical chiasmal visual field defect (bitemporal hemianopia, junction scotoma). In all patients, high-resolution computer-assisted tomographic (CT) scans of the sellar region were normal, and neither the medical history nor additional ophthalmological findings pointed to any explanation for the underlying disease. Six patients seemed to have suffered from chiasmal optic neuritis. Magnetic resonance imaging (MRI) scans could elucidate the diagnosis in five cases: white-matter lesions typical of multiple sclerosis (MS) were found and, additionally, in four cases an enlargement of the chiasm or barrier defect was revealed in post-gadolinium MRI. In one patient, MRI was normal. He recovered completely after megadose steroid therapy. One patient developed motoric symptoms of MS during the following year, another patient had mild sensory symptoms and recurrence of severe optic neuritis. An MR-proven chiasmal lesion due to a leukocytoclastic immunovasculitis combined with small subcortical white-matter lesions was diagnosed in another patient. The field defects disappeared spontaneously. In a 28-year-old woman a low vitamin B12 level was found in routine blood samples. Parenteral vitamin B12 substitution led to an almost complete recovery of the visual field defects. Chiasmal optic neuritis may occur isolated or during the course of MS. Megadose steroids may be of value if contraindications have been ruled out. A chiasmal visual field defect caused by vitamin B12 deficiency is very uncommon. A similar case was reported in 1961. PMID- 8220106 TI - Effect of topical 0.5% timolol on tear flow in patients with primary open-angle glaucoma as assessed by fluorophotometry. AB - The question as to whether or not topical medication with beta blockers causes a decrease in tear production remains unanswered. Earlier studies using filter paper strip tests have yielded contradictory results. In the present study, computerized objective fluorophotometry was used to assess the effect of topical medication with 0.5% timolol (b.i.d.; OU) on tear volume and tear production in 24 consecutive patients with bilateral primary open-angle glaucoma. Tear-film fluorophotometry was performed before treatment as well as at 7 days, 14 days, and 4-7 months after the onset of treatment. The results showed that by 7 days after the initiation of timolol treatment, both tear volume (-29%, P < 0.01) and tear secretion (-36%, P < 0.01) had decreased significantly. However, at both 14 days and 4-7 months after the onset of treatment, none of the values differed significantly from those obtained before treatment. Thus, topical antiglaucomatous treatment with 0.5% timolol eye drops leads to a transient decrease in tear production. This effect, however, lasts no longer than 14 days after the beginning of treatment. PMID- 8220107 TI - Influence of stimulus size and contrast on the temporal parameters of saccadic eye movements: implications for road traffic. AB - Saccadic eye movements are required for the recognition of peripheral objects in road traffic. Their latencies largely determine reaction time in emergency situations. The aim of this study was to investigate the influence of stimulus and surround parameters on the temporal characteristics of saccadic eye movements under conditions of object size, contrast and luminance corresponding to nighttime traffic. Square stimuli of 1 degree or 5 degrees size were presented under an eccentricity of 5 degrees and 15 degrees. The luminance of the surround was 4 x 10(-4) cd/m2 and 1 cd/m2. More than approx. 2,000 saccades of 7 normal subjects were registered and evaluated with respect to the latency, maximal velocity, and frequency of secondary saccades. At high stimulus contrast, latency approaches a minimum of approx. 200 ms. Latency increases with decreasing contrast up to maximal values of more than 600 ms. Transforming the contrast values into a relative decibel scale shows that this increase in latency occurs at significantly higher relative contrast values under scotopic as compared with photopic conditions. Our results demonstrate that an overall latency of 200-300 ms is not adequate for the assessment of accidents, especially under the stimulus conditions of nighttime traffic. PMID- 8220108 TI - Horizontal and vertical reading: a comparative investigation of eye movements. AB - Electronystagmographic (ENG) recordings of eye movements were made during the horizontal and vertical reading of a standardized text. The text was rotated to one side through an angle of 90 degrees for vertical reading. A total of 35 normal subjects was investigated under identical conditions. The following differences were found: A "staircase" pattern of successive, remarkably regular eye jerks was observed during horizontal reading. The reading speed was significantly higher in the horizontal direction. Vertical eye movements during vertical reading were less regular and showed a greater number of small jerks of varying size. No significant difference in reading speed between the two vertical directions was found. The search coil method (Robinson), which was employed in one subject, yielded much more accurate recordings than did the ENG. As a control experiment for vertical reading, the letters were rotated through 90 degrees. Reading this transposed text took twice as long as reading a 90 degrees-rotated text. PMID- 8220109 TI - Growth hormone: neurocrine and neuroendocrine perspectives. PMID- 8220110 TI - Platelet derived growth factor/tyrosine kinase receptor mediated proliferation. AB - PDGF heterodimer of A and B chains, a complete mitogen for 3T3 mouse fibroblasts, exemplifies those growth factors interacting with membrane associated tyrosine kinase receptors. Its binding to the PDGF-receptors results in receptor dimerization and subsequent activation of tyrosine kinase activity in the cytoplasmic protein domain, autophosphorylation of the receptor being the first event in the transduction cascade. Before the ligand-receptor complex is internalized and degraded, receptor stimulation is transmitted to the general transduction network, in which several tyrosine kinase substrates are activated by phosphorylation and changes the cytoplasmic biochemistry. These changes include cytoplasmic alkalinization, increases in the intracellular concentration of cyclic-AMP and Ca2+ and activation of protein kinase C through the degradation of phosphoinositides. The known substrates recruited by the PDGF-receptor association are phosphatidylinositol-3'-kinase, ras-GTPase-activating protein, phospholipase C-gamma, serine-threonine kinase Raf-1 and src and src-related tyrosine kinases. Upon binding of PDGF to its receptor, transactivation of transcriptional and nuclear factors such as c-fos and c-myc genes and dephosphorylation of c-jun occurs, V-sis, the oncogen of the simian sarcoma virus (SSV), is highly homologous to the c-sis/PDGF-B gene that encodes the homodimer of the B-chain of the PDGF receptor. Cells transformed by SSV have been studied as a model system for the autocrine stimulation of the PDGF receptor. PMID- 8220111 TI - Specific somatotropic and lactogenic uptake in vivo in the livers of transgenic mice expressing bovine growth hormone gene. AB - The distribution of labeled hGH, oGH and mPRL in different tissues of MT-bGH transgenic and normal mice was investigated using an in vivo technique. This technique allows comparisons of tissue uptake of radioactivity after the labeled hormone was injected alone (20 ng/50 g BW) or together with an excess (300 micrograms/50 g BW) of unlabeled hormone. Liver, kidney and spleen are the organs that concentrate a significant amount of radioactivity 20 min after the injection of labeled hormones, but the uptake of radioactivity decreased in the presence of unlabeled hormones only in the liver. Graphical analysis showed that the disappearance curves were described by the sum of 3 compartments alpha, beta and gamma. The first two are similar in transgenic and in normal mice but the third had a t1/2 of 56 +/- 9 min in transgenic and 71 +/- 8 min in normal mice. The inhibition of liver uptake was related to the dose of unlabeled hormone injected and a half maximal displacement was obtained with 4 micrograms and 10 micrograms of hGH per 50 g of body weight for normal and transgenic mice, respectively. The 125I-hGH taken up in vivo by the liver of transgenic mice was bound to a molecular species with Stokes radius of approximately 64 A (which is consistent with the molecular size reported for the hormone-receptor complex).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8220112 TI - Non-Hodgkin's lymphomas in elderly patients. AB - Based on population statistics and institutional reviews, the median age of patients developing non-Hodgkin's lymphomas (NHL's) is around 65 years. A review of retrospective studies suggesting that increasing age imparts an adverse prognosis in patients with NHL's is presented. Interpretation of this data is often confounded by referral bias of patients to specialized centres, multiple other NHL-related risk factors and inadequate chemotherapy administration due to age and toxicity related dose reductions. These factors, as well as alterations in tumour-host biology and comorbid diseases which result in changes in pharmacokinetics and pharmacodynamics, are discussed as possible reasons for poorer outcome in the elderly. In an effort to develop better tolerated and thus more effective combination chemotherapy for older patients, a number of prospective single arm and randomized clinical trials of novel regimens have been undertaken. Improved rates of disease remission and overall survival appear often to have been achieved at the expense of greater morbidity and mortality. Ongoing attempts to improve the therapeutic index include the application of chronic oral chemotherapy, brief duration intensive therapy and fractionation of standard drug doses as well as incorporation of myelo-preserving haematopoietic growth factors. The possibility of developing flexible, "customized" therapy for elderly patients is discussed. PMID- 8220113 TI - Somatic point mutations in the translocated bcl-2 genes of non-Hodgkin's lymphomas and lymphocytic leukemias: implications for mechanisms of tumor progression. AB - The t[14;18] chromosomal translocation is the most common cytogenetic abnormality found in hematolymphoid malignancies. The t[14;18] fuses the bcl-2 gene at 18q21 with the immunoglobulin heavy-chain locus at 14q32, resulting in deregulated expression of bcl-2 and production of high levels of its encoded 26-kD protein in the majority of non-Hodgkin lymphomas. Recent data indicate that somatic point mutations frequently occur in translocated bcl-2 alleles, possibly because of the somatic hypermutation mechanism that is associated with the immunoglobulin gene loci and that normally contributes to antibody diversity. In some cases, these mutations can affect the open reading frame of the bcl-2 gene and thereby alter Bcl-2 proteins. Here, we review the currently available data about the incidence, biological effects, and possible clinical importance of somatic mutations within the translocated bcl-2 genes of human lymphomas and leukemias. PMID- 8220114 TI - Chronic myeloid leukemia: management of relapse after allogeneic bone marrow transplantation. AB - The management of chronic myeloid leukemia (CML) patients who relapse after allogeneic bone marrow transplantation (BMT) is difficult. Hydroxyurea, alpha interferon, second BMT and leukocytes infusion are various options but none of these approaches is clearly optimal. Hydroxyurea controls the symptoms in most patients without any apparent survival benefit. Alpha interferon (IFN) results in haematological remission in most cases with partial or total Philadelphia negativity in 20-30% of patients. Whether IFN therapy prolongs survival is not yet certain. Second BMT results in successful outcome in about half of the patients, however toxicity to the preparatory regimen, post transplant venocclusive disease and acute graft versus host disease are all major complications. An interval of less than 6 months between the initial and second BMT is generally associated with a poor outcome. Buffy coat infusions from the original donor have resulted in a cytogenetic remission in most patients. Less intensive preparatory regimes, donor buffy coat infusion and the use of biological response modifiers post transplant in order to augment the graft versus leukemia effect in high risk patients may indeed be possible areas of improvement in future studies. PMID- 8220115 TI - rhGM-CSF after allogeneic bone marrow transplantation from unrelated donors: a pilot study of cyclosporine and prednisone as graft-versus-host disease prophylaxis. AB - Cyclosporine and prednisone were administered as graft-versus-host disease (GVHD) prophylaxis to nine patients undergoing marrow transplant from HLA matched, unrelated donors. RhGM-CSF was administered at a dose of 250 micrograms/m2 daily to all patients. The median day of neutrophil recovery to > or = 500/mm3 was Day 16. Four patients developed Grade II acute GVHD and four developed Grade III acute GVHD. One patient, who survived only 25 days, did not develop GVHD at all. One patient developed systemic infection within the first 28 days after marrow infusion. Comparison of these data to a prior series of patients undergoing bone marrow transplant (BMT) from unrelated donors who were treated with rhGM-CSF along with methotrexate and cyclosporine for GVHD prophylaxis suggests that rhGM CSF is well-tolerated, neutrophil recovery may be earlier but the severity of GVHD does not appear reduced. Selection of the GVHD prophylaxis regimen may affect the hematopoietic response to cytokine therapy. Further trials with rhGM CSF in patients undergoing BMT from unrelated donors are required. PMID- 8220116 TI - Effects of rhGM-CSF on myeloid clonogenic cells in acute myelogenous leukemia patients. AB - The effects of rhGM-CSF in vivo on the myeloid clonogenic cells present in 6 AML patients was evaluated. The relative number of clonogenic cells fell in 4 of the 6 patients. The effects of rhGM-CSF on the percentage of clonogenic cells in S phase and the sensitivity of clonogenic cells to cytosine arabinoside varied among the patients. These effects were not related to the effects of rhGM-CSF on the white blood cell count or on the proliferative rate of the leukemia cell population as a whole. PMID- 8220117 TI - Phase II clinical trial of fludarabine in chronic lymphocytic leukemia on a weekly low-dose schedule. AB - The major complication during therapy of chronic lymphocytic leukemia (CLL) with the purine nucleotide analogue fludarabine is infection, which is also the main cause of morbidity and mortality in the disease. As the incidence of infectious episodes during therapy correlated with severity of neutropenia, stage of disease, and response to therapy, an effort was made to reduce therapy-related myelosuppression and improve response by altering the conventional therapy regimen. The protocol which yielded a response rate of 57% in previously treated patients with CLL consisted of five consecutive daily doses of 25-30 mg/m2 fludarabine given every three to four weeks. Based on observations from intracellular pharmacology studies it was hypothesized that repetitive single weekly doses of fludarabine would allow normal bone marrow cells to recover while maintaining cytotoxic levels in the leukemic cells. The cumulative four-week dose of the once-weekly regimen was approximately 80% of the original protocol. Eleven out of 46 evaluable patients (24%) responded to the therapy. Seven patients (15%) achieved a complete remission, and four (9%) a partial remission. While myelosuppression was reduced by about 30% compared with the original protocol, the incidence of febrile episodes was increased by 17%. Pretreatment serum IgG levels below the normal range correlated significantly with a high incidence of infectious episodes and with a short median survival time. These observations suggest that in addition to myelosuppressive therapy, disease related depressed immune function causes morbidity and mortality due to infections. The results further show that changes in the scheduling of the therapy regimen, associated with a slightly lower dose, resulted in reduced efficacy as measured by the response rate. PMID- 8220118 TI - Treatment of chronic myelogenous leukemia in blast crisis and in accelerated phase with high- or intermediate-dose cytosine arabinoside and amsacrine. AB - Twenty-two patients (mean age 41 years) in blast crisis or accelerated phase (AP) of chronic myelogenous leukemia (CML) were treated with cytosine arabinoside (Ara C) 500 mg/m2 [intermediate dose] or 1000 mg/m2 [high dose] twice a day for 6 days and amsacrine (AMSA) 120 mg/m2 for 3 days. Twenty-one cases were of myeloid type and one was a lymphoid BC. The mean duration of aplasia (neutrophils < 0.5 x 10(9)/l) was 21.5 days. Four patients (18%) died of infection during aplasia and minor toxicities were noted for the remainders. Nine patients (41%) achieved a complete remission (CR) and 4 (18%) a partial response. Various additional therapies were proposed after induction treatment including allogeneic bone marrow transplantation (2 patients), Ara-C and AMSA maintenance or other regimens with or without alpha-interferon (9 patients). Median survival for the entire cohort was 20 weeks (wks), significantly superior for complete responders (37 wks) than for others (7 wks) (p = 0.008). In this study, age, sex, initial platelet or basophil counts, interval between diagnosis of CML and blast crisis were not predictive of response. Although inducing a high CR rate and associated with acceptable toxicity, this regimen did not improve the survival of patients with BC or CML, strengthening the need for alternate approaches to be defined. PMID- 8220119 TI - Surface phenotype and adhesion activity of B-cell chronic lymphoid leukemias. AB - Surface phenotypes and adhesion activity to human umbilical vein endothelial cells (HUVECs) were studied using leukemic cells from 12 Japanese patients with B cell chronic lymphoid leukemias including 7 with chronic lymphocytic leukemia (CLL), 1 with prolymphocytic leukemia (PLL), 2 with hairy cell leukemia (HCL) and 2 with HCL variant (HCL-V). CD13 and CD23 were found to be characteristically positive in CLL, whereas they were not expressed in non-CLL cases except for positivity of CD23 in two such cases. Except for CD11b, all other leukocyte integrins examined (CD11a, CD11c and CD18) and their ligand (CD54) were highly expressed in non-CLL cases. Adhesion activity of leukemic cells to HUVECs after co-culture with HUVECs was well correlated with the expression of CD11b, CD18 and CD54, but showed no predilection for any leukemia subtype. Positivity for CD5, CD21, CD23 and CD13 changed after the co-culture with HUVEC. These results suggest that adhesion activity after co-culture. does not correlate with the leukemia subtype and that endothelial cells activate or differentiate leukemic cells. PMID- 8220120 TI - Lack of involvement of T-lymphocytes in the leukaemic population during prolonged chronic phase of Philadelphia chromosome positive chronic myeloid leukaemia. AB - Nine patients with prolonged (> 2 years) chronic phase chronic myeloid leukaemia (CML) were investigated for the presence of T-cell involvement in the leukemic clone. Pure populations of peripheral blood T-cell populations were obtained by culturing separated mononuclear cells in the presence of pokeweed mitogen and IL2, until cultures showed > 99% pure T-cells. Purified T-cells and bone marrow and peripheral blood hematopoietic precursors were analysed for the presence of bcr-abl mRNA transcripts following RNA extraction and message amplification using polymerase chain reaction. In none of the 9 patients was bcr-abl mRNA found in T lymphocytes while in all cases such transcripts were found in bone marrow and peripheral blood hematopoietic cells. Failure to detect T-cell involvement in patients with prolonged chronic phase CML using techniques designed to enhance even low level involvement of these cell populations supports the view that acquisition of the Ph chromosome abnormality does not occur in the totipotent stem cells but in more committed precursor cell/s with multilineage capacity but which only rarely retain the capacity for T-cell differentiation. PMID- 8220121 TI - Immunoglobulin gene rearrangement in plasma cell dyscrasias: detection of small clonal cell populations in peripheral blood and bone marrow. AB - The bone marrow (BM) and peripheral blood (PB) samples of 71 patients with plasma cell dyscrasias were analysed by the Southern blot technique for the presence of clonal immunoglobulin (Ig) gene rearrangements. 53% of BM samples examined were archival material such as air dried BM slides or frozen trephine biopsies. The results were related to bone marrow plasmacytosis as determined by cytology and flow cytometry, and other clinical parameters. Clonal Ig gene rearrangements were found in BM samples of 45 (83%) of 54 MM patients and in 3 of 6 patients with monoclonal gammopathy of unknown significance (MGUS). Clonal cell populations in the PB were detected in 11 (30%) of 37 examined MM patients, but in none of the patients with MGUS or solitary plasmacytoma of bone. PB involvement was associated with progressive disease. Circulating monoclonal cells were significantly associated with higher M-protein levels (p < 0.05). Thus, circulating clonal precursor cells are encountered more frequently in active MM. PMID- 8220122 TI - Sinonasal malignant lymphoma of natural killer cell phenotype associated with diffuse pancreatic involvement. AB - We report a case of sinonasal lymphoma with a natural killer (NK) phenotype. This 40-year-old man was admitted to our hospital because of left nasal obstruction. Physical examination and computed tomography of the skull revealed a tumor in the left nasal cavity and maxillary sinus. Histopathological examination revealed a diffuse proliferation of pleomorphic lymphoid cells. Imprint cytology showed that tumor cells contained some azurophilic granules, and expressed CD2, CD8, CD16, CD56 and HLA-DR antigens with little expression of other lymphoid or myeloid markers. Southern blot analysis revealed germline configuration for immunoglobulin heavy chain and T-cell receptor genes. These findings indicated that these cells were in fact NK cells. The patient's enlarged pancreas was also involved by lymphoma and the pattern of involvement simulated that seen in primary pancreatic lymphoma. Ulcerative colitis (UC) was also present, a rare finding in this disorder. PMID- 8220123 TI - Partial trisomy 1q, an uncommon chromosomal aberration in erythroleukemia. AB - A 2 years 4 months old boy with erythroleukemia (FAB-M6) and Down's syndrome is described. Chromosome analysis of bone marrow leukemic blasts revealed apart from the trisomy 21 a partial trisomy of the long arm of chromosome 1:1q23-->1qter in all cells and trisomy 8 mosaicism. To the best of our knowledge this is the first time that a partial trisomy of chromosome 1 in association with erythroleukemia has been described. Previous reports of other hematologic malignancies with aberrations of chromosome 1 indicate that the breakpoint 1q23 is nonrandom and that trisomies of chromosome 1 plays a crucial role in the course of development of hematologic malignancies. This could probably also be true for erythroleukemias. PMID- 8220124 TI - Excessive hepatitis-B surface antigen production after corticosteroids and the development of immunoblastic lymphoma. AB - The development of B-cell immunoblastic lymphoma in a 51 year old patient with hepatitis B virus related immune complex nephritis is described. The lymphoma was diagnosed eleven months after the administration of high dose corticosteroids which resulted in a striking increase in the HBsAg serum titer up to 1:1,000,000. This unusual association raises a number of interesting questions regarding the link between immune complex nephritis and immunoblastic lymphoma. The significance of corticosteroid therapy leading to excessive HBsAg secretion and the role played by this intense antigenic stimulation in the pathogenesis of lymphoma in this particular patient are also discussed. PMID- 8220125 TI - Splenectomy in lymphoproliferative disorders: a report on 70 cases and review of the literature. AB - Between February, 1970 and September, 1991, we performed splenectomies on 70 patients with chronic lymphoproliferative disorders including primary leukemias: 19 B-cell chronic lymphocytic leukemia, 1 B-cell prolymphocytic leukemia, 22 hairy cell leukemias, 4 large granular lymphocytic leukemias, 1 T-cell prolymphocytic leukemia, and non-Hodgkin's lymphomas (NHL): 10 splenic lymphomas with villous lymphocytes, 4 follicular lymphomas, 5 mantle cell lymphomas, 3 lymphoplasmacytic and 1 large cell NHL. The primary indications for surgery in this series were therapy-resistant disease (40%) and therapeutic splenectomy (38%). Postsplenectomy, 70% of patients had a complete hematological response, 23% had a partial response, and 7% were nonresponsive. Median treatment-free survival correlated with the hematologic response postsplenectomy and the underlying diagnosis. Better treatment-free survivals were seen in patients with lesser degrees of anemia and thrombocytopenia. Overall, improvements were more pronounced in the B-cell than in the T-cell disorders. Indications for further therapy, postoperative morbidity and mortality, and survival times are discussed along with a review of the literature. These findings advocate a continuing role for splenectomy in symptomatic lymphoid malignancies running with splenomegaly and hypersplenism. PMID- 8220126 TI - Genotypic heterogeneity of node based peripheral T-cell lymphoma. AB - PTCL represents a diverse group of histological entities that defy classification schemes based on normal T cell differentiation, differ in their clinical presentation and behave unpredictably. Genetic analyses of this phenotypically heterogeneous group have clearly shown that histologically defined PTCL may be subdivided on the basis of clonal gene rearrangements. The absence of clonal gene rearrangements in a significant proportion of PTCL cases has increased the complexity of classification. The data presented in this review suggest that a molecular classification would allow true reflection of PTCL aetiology, but carefully coordinated studies are required to evaluate the clinical usefulness of such a classification scheme. PMID- 8220127 TI - Magnetic resonance imaging in patients with bone marrow disorders. AB - Magnetic resonance imaging (MRI) provides a non-invasive means to evaluate a large fraction of marrow in less than one hour. Marrow disorders produce non specific changes in marrow signal intensities which primarily reflect changes in proportions of fat and cellular elements. The pattern of these signal changes narrows the differential diagnosis, and the combination of these features with the clinical context allows interpretations which are clinically useful in many ways. These include: 1) the diagnosis of avascular necrosis (and its distinction from other causes of joint pain), 2) detection of osteomyelitis, 3) differential diagnosis of hypoplastic disorders, 4) staging of lymphomas and myeloma, 5) selection of patients for autologous bone marrow transplant, 6) objective measures of marrow response to therapy, 7) detection of leukemic transformation, and 8) improved detection of marrow disease (primary or secondary) in patients with otherwise unexplained bone pain. PMID- 8220129 TI - Prognostic factors of invasive pulmonary aspergillosis in leukemic patients. AB - The study objective was to identify prognostic factors associated with survival in patients treated for acute leukemias who developed invasive aspergillosis (IA) during induction therapy. This retrospective analysis involved 21 patients treated in two hematologic centers over a six-year period. All were treated in protective isolated rooms with high-dose amphotericin B as soon as fungal infection was suspected. Ten (45%) of the twenty-one patients died. There was no statistical difference between the patients who survived and those who died in relation to the mean time of onset of IA or the total and mean daily dose of amphotericin B. On the other hand a favourable outcome correlated strongly with complete leukemic remission (p < 0.0001): all but one of the patients with objective residual leukemia died of IA, whereas all those who achieved complete hematological remission survived. In conclusion, it seems that the main vital prognostic factor in these leukemic patients with IA was the achievement of complete remission. We were unable to control IA in 10 of 11 patients with refractory leukemia, regardless of neutropenic status, despite early administration of high-dose amphotericin B. All the patients who achieved complete remission were successfully treated with amphotericin B. PMID- 8220128 TI - Acute megakaryoblastic leukemia in children and adolescents: a retrospective analysis of 24 cases. AB - In order to characterize the clinical, cytogenetic, and outcome features of childhood acute megakaryoblastic leukemia (AMKL), we reviewed 24 cases; 14 were identified among 150 consecutive newly diagnosed acute myelogenous leukemia (AML) patients at St. Jude Children's Research Hospital, and 10 were cases referred to the National Institute of Cancer in Rio de Janeiro, Brazil. There were 5 Down syndrome patients and one patient with chronic myeloid leukemia (Ph+) in blastic crisis. Twelve patients had significant hepatosplenomegaly. Leukemic cell morphology and cytochemistry were consistent with the M7 classification in 17 cases, and all cases tested expressed megakaryocytic surface antigens. AMKL patients were significantly younger than other AML patients (P = 0.0001) and had poorer responses to therapy (P = 0.03, univariate analysis only). Ten of 24 failed induction, and only 5 are disease-free at 6 months to 4.5+ years. We conclude that AMKL usually affects young children, frequently producing marked organomegaly. It comprises approximately 10% of pediatric AML cases, and responds poorly to intensive AML therapies. PMID- 8220130 TI - In vivo accumulation of etoposide in peripheral leukemic cells in patients treated for acute myeloblastic leukemia; relation to plasma concentrations and protein binding. AB - Since etoposide interacts with the nuclear enzyme topoisomerase II, the drug concentrations in the malignant cells during chemotherapy may have clinical correlates. Plasma protein binding of etoposide is extensive (94%) and alterations of the non-proteinbound fraction affect pharmacokinetic behavior of the drug. The pharmacokinetics of etoposide was therefore studied in plasma, total and non-proteinbound concentrations, and in leukemic cells isolated from peripheral blood samples from 22 patients after the first dose of the induction treatment for acute myelocytic leukemia. Fourteen patients received 100 mg/m2 and eight patients 200 mg/m2 as a 1 h infusion. The mean area under the concentration versus time curve AUC(0-infinity) in plasma was at the lower dose level 78.4 +/- 29.1 (mean +/- S.D.) micrograms/ml x h and 201.0 +/- 56.5 micrograms/ml x h at the higher dose level. The fraction of non-proteinbound etoposide in plasma was 5.2 +/- 3.4 and 5.4 +/- 2.1% in the two treatment groups. AUC(0-16h) in leukemic cells was 8.4 +/- 8.7 and 22.4 +/- 12.1 micrograms/ml x h at the two dose levels, respectively. The cellular etoposide concentration was 12.1 +/- 7.9 and 14.7 +/- 5.1% of the plasma concentration at the end of the infusion. The interpatient variability in cellular drug levels was considerable and exceeded the variability in plasma concentrations. Cellular accumulation of etoposide could be important for treatment outcome. PMID- 8220131 TI - NOPE for relapsed aggressive diffuse non-Hodgkin's lymphoma. AB - Forty three patients with relapsed, diffuse aggressive lymphoma (Working Formulation Categories G to J) were treated with a combination chemotherapy regimen consisting of mitoxantrone 10 mg/m2 iv day 1, vincristine 1.4 mg/m2 iv day 1 and 14, prednisolone 50 mg/m2 p.o. days 1-5 and etoposide 100 mg/m2 p.o. days 1-5 of each cycle (NOPE). Fourteen patients (34%) achieved complete remission and another 6/43 (15%) achieved a partial response. Factors which significantly affected response were the presence of early stage, absence of systemic symptoms, non-bulky disease and serum LDH value < 350 IU. Four patients are alive and in complete remission from 25+ to 45+ months after completion of therapy. Duration of response and survival was significantly influenced by the duration of the initial response to first chemotherapy. NOPE is an active and safe treatment regimen with a substantial complete remission rate in patients with relapsed non-Hodgkin's lymphoma. PMID- 8220132 TI - Differences in clinicopathological characteristics and major prognostic factors between B-lymphoma and peripheral T-lymphoma excluding adult T-cell leukemia/lymphoma. AB - A total of 541 consecutive patients treated between 1975 and 1985, 449 with B lymphoma and 92 with peripheral T-lymphoma, excluding adult T-cell leukemia/lymphoma (ATL), termed peripheral non-ATL T-lymphoma, were analysed. Clinicopathological features that were predominantly associated with B-lymphoma were low and intermediate grades (defined by the Working Formulation), diffuse large cell type, stage II disease, bulky disease, favourable extranodal sites that are defined as a group of primary tumors such as the eye, Waldeyer's ring, thyroid, and stomach, while other features predominantly associated with peripheral non-ATL T-lymphoma were high grade pathology, diffuse mixed-cell and immunoblastic type, systemic "B" symptoms, poor performance status (PS), generalized lymphadenopathy, involvement of organs such as liver, skin, and nose, leucocytosis, and a high levels of serum alkaline phosphatase. The survival curve for B-lymphoma was better (P < 0.01) than that for peripheral non-ATL T-lymphoma. Multivariate analysis revealed that the major prognostic factors were pathology, stage, and primary site for B-lymphoma, while stage, PS, and total protein levels were important for peripheral non-ATL T-lymphoma. These results indicate that B- and peripheral non-ATL T-lymphomas appear to have different biological characteristics. PMID- 8220133 TI - VAD regimen in the treatment of resistant multiple myeloma: slow or fast infusion? AB - The VAD regimen is effective in the treatment of resistant and relapsing multiple myeloma. In the original VAD regimen, vincristine (V) and doxorubicin (A) are given as continuous infusions together with peroral dexamethasone (D). For practical reasons, we have shortened the infusion times: 8 hours for vincristine and 1 hour for doxorubicin. In this retrospective analysis, we have compared the efficacy and toxicity of the original and modified VAD protocols in the treatment of myeloma patients at our institution. Of the 31 consecutive patients with myeloma, primarily or secondarily resistant to alkylating agents, 16 were treated by the original and 15 by the modified VAD protocol. We found no significant difference in the response rates (good responses 31% and 20% respectively), survival times (17 and 9 months respectively) or toxicity between the two protocols. VAD may well be modified so as to consist of short infusions of V and A. The overall efficacy of the traditional and modified regimens is, however, rather unsatisfactory in patients with advanced myeloma. PMID- 8220134 TI - Primary malignant lymphoma of the liver. AB - Clinical and pathologic features of 69 cases with primary hepatic lymphoma, 52 reported from Western countries and 17 cases from Japan, were summarized in terms of clinical findings including age and sex, past history, presenting symptoms, and physical findings, diagnostic procedures including imaging techniques and histopathology, and finally therapy and follow-up. The present cases included four patients with an acquired immunodeficiency syndrome and 12 with a history of chronic liver diseases. Histologically, all cases were non-Hodgkin's lymphoma with diffuse large cell type being the most common immunochemically about 80% were B-cell type. Follow-up showed that hepatic lymphoma had a relatively favourable prognosis provided early detection was possible. PMID- 8220135 TI - Multiparameter approach in the identification of cross-contaminated leukemia cell lines. AB - A common problem in cell culturing is cross-contamination with other cells or misidentification of cells. An effective cell culture quality and identity control is required in order to avoid inter- and intraspecies contamination of cell lines and their further propagation and dissemination. We present evidence that supposedly unrelated cell lines that we received from the original investigators are in fact related to the chronic myeloid leukemia cell line K 562. The sister cell lines SPI-801 and SPI-802 were originally established from a patient with T-cell acute lymphoblastic leukemia and displayed T-cell associated features. However, data from morphological evaluation, immunophenotyping, bcr-abl gene rearrangement analysis, DNA fingerprinting, Northern blot analysis of globin gene expression and esterase isoenzyme analysis clearly established that the three cell lines are related. Cytogenetic examination while not proving the common identity of the cells provided further evidence for the suspected common origin of all three cell lines. Chromosome banding, DNA fingerprinting and bcr abl genotyping suggested further evolution of these clones during long-term cultivation. Quality and identity control is an essential feature of cell culture technique. Only regular monitoring for purity and integrity of cell lines will significantly reduce the incidence of cell line contamination and misidentification. PMID- 8220136 TI - Candida tropicalis infections in children with leukemia. AB - The Candida species account for approximately three-fourths of fungal infections in patients with cancer. Although Candida albicans is the most frequent cause, C. tropicalis is increasingly implicated as an important pathogen. Over a 12 year period 19 children treated for leukemia at our institution developed C. tropicalis infections. We describe their clinical presentation, extent of fungal infection, treatment, and outcome. Fungemia without meningitis in 11 children was treated successfully, whereas C. tropicalis meningitis in 7 children was uniformly fatal. An additional patient had unsuspected, widespread infection detected at autopsy. Multiple sites, including the cerebrospinal fluid yielded C. tropicalis. Previously reported risk factors including neutropenia, broad spectrum antibiotic usage, corticosteroid therapy, and total parenteral nutrition were observed in our cases. A high index of suspicion and the early use of aggressive antifungal therapy are critical to the successful management of C. tropicalis infections in children with leukemia. PMID- 8220137 TI - Non-endemic Burkitt's lymphoma in a patient with Bloom's syndrome. AB - Bloom's syndrome is an autosomal recessive disorder characterized by intrauterine growth retardation, typical physical signs, immunodeficiency and an increased risk of developing neoplasms at a young age, compared to the general population. Factors possibly involved in the pathogenesis of non-endemic Burkitt's lymphoma in a five year old girl with Bloom's syndrome are discussed. These include immunodeficiency, upregulated c-myc expression and an Epstein-Barr viral infection. PMID- 8220139 TI - Myelosarcoma preceding acute leukemia diagnosed by fine needle lymph node aspiration: report of two cases. AB - Myelosarcoma (granulocytic sarcoma) is a rare tumor seen in patients with known hematologic malignancies such as leukemia, myelodysplastic syndromes and myeloproliferative disorders, as well as in non-leukemic patients. A correct diagnosis in these cases is often difficult, and these are more commonly misdiagnosed as large cell lymphoma. We describe two women, 40 and 89 years of age respectively, in whom a myelosarcoma involving the neck lymph nodes was diagnosed by cytological examination of a fine needle aspiration biopsy, one and 10 weeks before the onset of acute myelogenous leukemia. The fine needle aspiration technique allowed a quick and unexpected diagnosis to be made demonstrating granulocytic differentiation and the presence of myelo-monocytic cells within lymphatic tissue. The simplicity of the procedure, coupled with its reliability and rapidity suggest that fine needle aspiration biopsies should be used more widely as a first choice method in the diagnostic evaluation of palpable lymph nodes. PMID- 8220138 TI - Investigation of the expression of housekeeping genes in non-Hodgkin's lymphoma. AB - Studies of quantitative changes in gene expression in malignant cells have often used housekeeping genes as controls against which the level of expression of a gene under study could be compared. We have now examined whether the expression of the most commonly used of these housekeeping genes can be regarded as reliable controls for gene expression studies in non-Hodgkin's lymphoma (NHL). We have used Northern blot analysis to compare the levels of expression of beta-actin, alpha-tubulin, beta 2-microglobulin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to that of ribosomal RNA. These studies demonstrated that whereas there was a reasonable correlation between the relative levels of rRNA and housekeeping gene expression in reactive hyperplastic nodes, there were major differences in the relative levels of expression of the housekeeping genes in both low and high grade lymphomas; only GAPDH showed any degree of consistency. These observations indicated that housekeeping gene expression was not a reliable control for estimating changes in the level of expression of other genes in NHL, and instead suggested that 18S or 28S rRNA expression offered a more accurate method of RNA quantitation. PMID- 8220140 TI - Coexistent multiple myeloma and myelofibrosis. AB - Although the association of bone marrow fibrosis with plasma cell dyscrasias has already been described in several reports, the close relationship between these entities still remains unclear. In this report we describe a patient with clinical and pathologic findings which initially suggested a diagnosis of myelofibrosis, subsequently shown to be coexistent with multiple myeloma. Possible explanations for this association are discussed. PMID- 8220141 TI - Immature and differentiated neoplastic populations in acute lymphoid leukemia of childhood: biological and clinical implications. AB - Despite significant improvement in the therapy for acute lymphoid leukemia (ALL) of childhood, approximately 30% of patients relapse. Unfortunately, since no successful treatment for recurrent disease has been developed, the majority of these patients die. Recently, we presented evidence consistent with the presence of a limited program of differentiation in B-precursor ALL that is reminiscent of normal B-cell development. We found that ALL cell populations consist of both a subpopulation of progenitors with the immunophenotype of normal B-cell precursors that has self-renewal capability and a second subpopulation with a more mature early B-cell immunophenotype that is without self-renewal capability but can proliferate to a limited extent. In our recent studies we were able to grow the progenitor cells in the ALL blast colony assay and establish their leukemic origin using the polymerase chain reaction. Our results suggest that these progenitors are the cells that sustain the disease. We hypothesize that these cells may remain quiescent, for a time, and either eventually die or regain proliferative capability and cause relapse. Further studies aimed both at detecting residual ALL and determining changes in their biology may provide an understanding of the mechanisms of relapse in this disease. PMID- 8220142 TI - Idarubicin in the initial treatment of adults with acute lymphoblastic leukemia: the effect of drug schedule on outcome. AB - Fifty two adults (aged 15 to 66 years) with newly diagnosed acute lymphoblastic leukemia (ALL, n = 47) or lymphoid blast phase chronic myelogenous leukemia (Ly CML, n = 5) were managed with three distinct protocols containing idarubicin at a cumulative dose of 36, 20, and 10 mg/m2, respectively, plus vincristine, L asparaginase, and prednisolone (IVAP-1, -2, -3). IVAP-1 was highly toxic and gave a low complete remission (CR) rate (7/17, 41%). Nine patients died of complications while severely neutropenic, and one had resistant disease. In contrast, 24 of 28 patients subsequently treated with IVAP-2 achieved a CR (86%, p 0.005), the rate of both hematological and extrahematological toxicity being significantly reduced compared with IVAP-1 (p < 0.05). With IVAP-3, 6/7 patients aged > 60 years achieved CR. IVAP-2 with total idarubicin 20 mg/m2 is a very effective and well tolerated regimen for the initial treatment of adults with ALL. PMID- 8220143 TI - Pilot study and randomised trial of mitozantrone and ifosfamide for relapsed non Hodgkin's lymphoma. Scotland and Newcastle Lymphoma group (SNLG) Working Party on Therapy. AB - This report compares a pilot study followed by a trial of the combination of mitozantrone and ifosfamide for relapsed lymphoma. In the pilot study (15 patients) toxicity and activity of the combination was tested on a variety of relapsed non-Hodgkin's lymphoma. In the trial (19 patients) the therapy was confined to patients with high and intermediate grade non-Hodgkin's lymphoma in which the combination was compared against single agent mitozantrone. The median survival of patients on the pilot and trial was very poor at around six months, but some individuals survived for several years from both groups. The main toxicities of treatment were, predictably, nausea and vomiting and bone marrow suppression on the combination, and bone marrow suppression alone on the single agent mitozantrone. There was no obvious disadvantage of the single agent treatment when compared with the combination, but this statement has to be interpreted with caution given the high death rate amongst all patients and the very small numbers who entered the randomised trial. PMID- 8220144 TI - Third generation chemotherapy with P-VABEC for aggressive non-Hodgkin's lymphomas of the elderly. AB - Between July 1990 and March 1992, 23 elderly patients with intermediate or high grade non-Hodgkin's lymphomas (NHL) received a combination chemotherapy (P-VABEC: Etoposide, Adriamycin and Cyclophosphamide on days 1, 15, 29, 43, Vincristine and Bleomycin on days 8, 22, 36, 50 and Prednisolone on weeks 1-9). The regimen was administered on an outpatient basis. The median age of the patients was 67 years (range 60-78); 15 were previously untreated, 8 were on second line therapy; 6 patients (44%) had stage IV disease, 19 (83%) B symptoms, 15 (65%) had bulky disease, and (26%) bone marrow involvement. The complete remission (CR) rate was 57%, and the partial remission (PR) rate 43%, with an overall response rate of (100%). No difference in response rate was observed between previously untreated patients and patients treated with P-VABEC as second-line therapy while hematological and clinical toxicity were very mild. PMID- 8220145 TI - Clinical implication and prognostic significance of small lymphoma cells in the peripheral blood and bone marrow of B-cell non-Hodgkin's lymphomas. AB - It seems possible that small lymphoma cells (SLC) may have a role even in aggressive B-cell non-Hodgkin's lymphoma (B-NHL) such as large-cell lymphoma. However, SLC are often difficult to distinguish morphologically from normal or reactive small lymphocytes. In this study, we used a flowcytometric technique (kappa-lambda imaging; KLI) for detection of SLC. Peripheral blood (PB) and bone marrow (BM) samples taken from 41 patients with surface immunoglobulin positive (sIg+) B-NHL were analysed. SLC were detected in about 90% (37/41) of the untreated patients when either PB or BM was analysed by KLI. The presence of SLC correlated well with disease activity. However, a few SLC were present even in the PB (16%) or BM (27%) of the 31 patients who achieved complete remission, indicating that minimal residual disease (MRD) was present. In some cases, the reappearance of SLC in the PB or BM preceded clinical relapse. Furthermore, the initial volume of SLC, particularly in the BM, tended to be related to the prognosis (P = .068). These results suggest that the detection of SLC by KLI may be helpful not only for the screening and clinical staging of sIg+ B-NHL, but also for monitoring disease activity and detecting MRD. Moreover, the volume of SLC in the BM may be a useful predictor of prognosis. PMID- 8220146 TI - Large granular lymphoproliferative disease associated with nephrotic syndrome, renal failure and leukoencephalopathy. AB - A 23-year-old black female presented with general malaise, headache, high white cell count (136 x 10(9)/L), thrombocytopenia and nephrotic syndrome. She proved to have large granular lymphoproliferative disease with a natural killer cell phenotype and without a clonal rearrangement of the T-cell receptor genes. Renal biopsy demonstrated focal segmental glomerulosclerosis (FSGS). She developed a monophasic neurological illness, and rapidly became comatose six days after the initiation of high dose prednisone therapy. Computerized tomography of the brain showed marked hypodensity of the subcortical white matter. She regained consciousness subsequently, but died six months after her initial presentation with uncontrolled lymphocytosis and renal failure. Autopsy revealed FSGS with glomerular collapse and microcystic dilatation of the renal tubules, and there was perivascular demyelination in the subcortical white matter of the brain. We speculate that lymphokines released by the natural killer cells may have played an important role in the pathogenesis of both the nephrotic syndrome and leukoencephalopathy. PMID- 8220147 TI - Therapy-related acute myelogenous leukemia associated with 11q23 chromosomal abnormalities and topoisomerase II inhibitors: report of four additional cases and brief commentary. AB - We report 4 additional cases of therapy-related acute myelogenous leukemia (t AML) with the translocation t(9;11)(p22q23). Chemotherapy for the primary malignancy (breast carcinoma in 2, non-Hodgkin's lymphoma in 2) included agents with topoisomerase II inhibitory activity (doxorubicin in 2; doxorubicin and etoposide in 1; doxorubicin, etoposide and mitoxantrone in 1) as well as alkylators. In agreement with previous reports, the leukemia was monoblastic (FAB M5 subtype) in all 4 patients, with only 1 having prior myelodysplasia, and the latency period from primary therapy was relatively short (24-48 months). All patients received potentially curative treatment for the leukemia which included allogeneic bone marrow transplantation in 3; however, all died (3 of t-AML and 1 of lymphoma). Therapy-related AML associated with exposure to agents with topoisomerase II inhibitory activity (epipodophyllotoxins and anthracyclines) is a distinct entity, the genetic basis and optimal treatment of which remain to be determined. PMID- 8220148 TI - Remission of malabsorption in congenital intestinal lymphangiectasia following chemotherapy for lymphoma. AB - A 22-year-old female with protein losing enteropathy due to congenital intestinal lymphangiectasia who developed non-Hodgkin's lymphoma of the bone, is described. Complete remission of the lymphomatous process and disappearance of the gastrointestinal symptoms were achieved following treatment with combination chemotherapy and local irradiation. PMID- 8220149 TI - Translocation t(1;19) in acute lymphoblastic leukemia patients with cytological presentation simulating L3-ALL (Burkitt-like). AB - The t(1;19) in B-lineage ALL is classically associated with a FAB L1/L2 phenotype and the expression of cIg. Recent reports have demonstrated immuno-phenotypic and molecular heterogeneity among cases demonstrating apparently identical karyotypic abnormalities. We report 5 cases of t(1;19) with cytological features resembling an L3 (Burkitt-like) phenotype, suggesting that accurate assessment of these cases requires detailed correlation of cytological, immunological and molecular characteristics. PMID- 8220150 TI - Acute megakaryocytic leukemia with the t(1;22)(p13;q13). AB - Acute megakaryocytic leukemia (AMKL) was defined as a new subtype of acute nonlymphocytic leukemia (ANLL) by the French-American-British (FAB) Cooperative Group in 1985. The first consistent chromosomal anomaly described in this subset of ANLL was the translocation t(1;22)(p13;q13) which appears to be restricted to this FAB-subtype (FAB-M7) of AML. To our knowledge, 18 AMKL cases with the t(1;22) have been reported until now in the literature. In all instances, the patients were very young children with only one beyond the infant age (12 months) at the time of diagnosis. Based on the results of two reports in which the frequency of this translocation was assessed, the t(1;22) may be estimated to occur in about 30% of pediatric patients with FAB-ANLL subtype M7. In infants with this subset of ANLL, the t(1;22) seems to be present in the majority (> 65%) of cases. The detection of this nonrandom chromosomal abnormality may therefore provide an additional diagnostic marker in children with AMKL. Herein we review and discuss the clinical and cytogenetic findings in patients with AMKL and the t(1;22). PMID- 8220151 TI - Optic nerve involvement in acute lymphoblastic leukemia. AB - Leukemic infiltration of the optic nerve is rare. We describe the diagnostic assessment and the outcome in two adult patients suffering from acute lymphoblastic leukemia with T phenotype. In both cases the leukemic involvement of the eye was observed as an isolated extramedullary relapse followed after several months by hematological relapse. CT and MRI scans were negative, while an A-scan echography of the eye clarified the diagnosis. Early radiotherapy caused recovery of visual acuity in one case. A-scan echography is the most sensitive investigation for the early recognition of ocular localization in acute leukemias. PMID- 8220152 TI - Mutations of the p53 gene in B-cell lymphoma. AB - Mutations of p53 gene have been recognized to be the most common genetic changes in human cancers. Recently, p53 gene mutations have been found in some patients with common subtypes of B-cell lymphoma (9/48:18.8%), Burkitt lymphoma (9/27:33.3%) and chronic lymphocytic leukemia (6/40:15%). Evidences to suggest that p53 gene mutations are associated with the disease progression in B-cell lymphoma have emerged. Functions of wild-type p53 and its mutant's probable role in B-cell lymphomagenesis are described in this review. PMID- 8220153 TI - New insights into the pathogenesis of coagulation dysfunction in acute promyelocytic leukemia. AB - Patients with acute promyelocytic leukemia (APL) are at high risk for the development of life-threatening thrombotic and hemorrhagic complications, particularly during induction chemotherapy. This propensity has been attributed to the release of tissue factor (TF)-like procoagulants from the leukemic cells leading to disseminated intravascular coagulation (DIC). However, recent data suggest that the pathogenesis of the coagulopathy is more complicated and may involve activation of the generalized proteolytic cascade resulting in either clotting and/or excessive fibrinolysis. Furthermore, controversy exists regarding the mechanism(s) responsible for the activation of either clotting or fibrinolysis. The malignant promyelocyte may act directly to activate coagulation and/or fibrinolysis. Alternatively, reactive inflammatory cells, which express procoagulant and/or profibrinolytic activities may play an essential role. A third possibility may involve endothelial cell expression of mediators with procoagulant/profibrinolytic properties. Putative profibrinolytic mechanisms include the release of urokinase-type and tissue-type plasminogen activators, decreases in plasminogen activator inhibitor-1 and 2, and decreases in alpha-2 plasmin inhibitor. Putative procoagulant mechanisms include the release of tissue factor, Cancer Procoagulant, or cytokines such as interleukin-1, tumor necrosis factor and vascular permeability factor. Putative anticoagulant mediators include annexins, a group of proteins in human tissue which bind phospholipids and have anticoagulant activity, which have been reported in patients with APL. The current treatment of APL is rapidly evolving because of the efficacy of all-trans retinoic acid (ATRA). All-trans retinoic acid promotes terminal differentiation of leukemic promyelocytes leading to complete remission in the majority of patients with APL with rapid resolution of the coagulopathy. Although the mechanism by which this occurs has not been established, preliminary data suggest that ATRA blocks the downregulation of the thrombomodulin gene and the up regulation of the tissue factor gene induced by tumor necrosis factor. Since APL is a relatively uncommon disorder, the collaboration of cooperative oncology groups will be important to study patients receiving ATRA or conventional chemotherapy to further elucidate the mechanism(s) of the coagulopathy. PMID- 8220154 TI - Recommended procedures for the classification of acute leukaemias. International Council for Standardization in Haematology (ICSH). AB - The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukemia. PMID- 8220155 TI - Autoimmune hemolytic anemia in chronic lymphocytic leukemia patients treated with fludarabine. AB - Autoimmune hemolytic anemia (AHA) is a frequent complication of chronic lymphocytic leukemia (CLL). Although the pathogenesis of AHA is still unknown, an imbalance of normal residual T cells is believed to play a central role. Since fludarabine is reported to affect primarily T lymphocytes, we conducted a retrospective study to evaluate the incidence and outcome of AHA in 112 CLL patients treated with fludarabine alone. Eight patients had AHA before therapy; only one achieved remission of both CLL and AHA after fludarabine alone. In the other seven patients, we observed no effect or even a worsening of AHA, although the CLL was responding to fludarabine. Five patients developed AHA from 1 to 19 months after fludarabine therapy while the CLL was responding. One additional patient developed pure red cell aplasia (PRCA) 3 months after starting therapy. Most patients in both groups responded to steroids or other immunosuppressive therapy. The study showed that in these patients, AHA evolved independently of CLL and was not affected by fludarabine. PMID- 8220156 TI - Effect of induction cytarabine dose intensity on long-term survival in acute myelogenous leukemia: results of a randomized, controlled study. AB - The optimal dose and schedule of cytarabine in induction chemotherapy of newly diagnosed acute myelogenous leukemia is not established. We compared the use of cytarabine 200 mg/m2/day by continuous infusion for seven days to an intermediate dose of cytarabine, 500 mg/m2 every 12 hours for 12 doses. Thirty-seven of 52 patients assigned to conventional-dose cytarabine achieved complete remission (71%) and the actuarial disease-free and overall survival after achieving remission were 22 +/- 16% and 31 +/- 19% respectively. Thirty-seven of 50 patients assigned to intermediate-dose cytarabine achieved remission (74%) and the actuarial disease-free and overall survival after achieving remission were 26 +/- 16% and 39 +/- 18% respectively. There were no statistically significant differences in complete remission rate, actuarial leukemia-free survival or overall survival between the groups. The most significant predictor for survival was age. Actuarial two year leukemia-free survival and overall survival for patients age > 60 were 8 +/- 15% and 20 +/- 19% respectively compared to 36 +/- 14% and 54 +/- 15% for patients age < or = 60 (P = .058 and .01, respectively). Induction regimen did not significantly affect disease free or overall survival for patients under or over age 60. We conclude that intermediate-dose cytarabine did not substantially improve results of induction for newly diagnosed acute myeloid leukemia. PMID- 8220157 TI - Role of aberrant sialylation of chronic myeloid leukemia granulocytes on binding and signal transduction by chemotactic peptides and colony stimulating factors. AB - Chronic myelogenous leukemia (CML) granulocytes exhibit a number of characteristics attributable to immature granulocytes, including marked increases in cell surface sialylation of glycoproteins which may be due, at least in part, to an increased activity of cytidine 5'-monophosphate-N-acetylneuraminic acid:Ga1 beta 1-3Ga1NAc alpha(2-3)-sialyltransferase (EC 2.4.99.4), and perhaps to altered activity of other glycosyltransferases and sialidases. This aberrant sialylation of CML granulocytes contributes to the decreased binding of the synthetic chemotactic peptide, formyl Met Leu Phe (fMLP), to the surface of CML granulocytes which leads to a rapid, transient increase in cytosolic free calcium ([Ca2+]i), an integral step in the biochemical cascade leading to cell activation. To determine if the decrease in binding of fMLP to CML granulocytes translates into a functional deficit, we measured fMLP-induced increases in [Ca2+]i. Compared to normal granulocytes, fMLP-induced increases in [Ca2+]i were markedly decreased in CML granulocytes. After sialidase treatment, a significant augmentation in fMLP-induced increases in [Ca2+]i was noted in CML granulocytes, indicating that the decreased signalling may be a consequence of aberrant sialylation. To determine if the effects of aberrant sialylation also alters the binding of endogenous polypeptide mediators, we determined the effect of desialylation of CML and normal granulocytes on binding of the colony stimulating factor for granulocytes and monocytes (GM-CSF), which plays a role in differentiation and proliferation of myeloid-lineage cells. As with fMLP binding, we also showed that the binding of GM-CSF to CML granulocytes, but not normal granulocytes, was markedly increased after sialidase treatment. Similarly, binding of GM-CSF to undifferentiated HL-60 cells was markedly increased after sialidase treatment. Therefore, we have demonstrated that aberrant sialylation of CML granulocytes not only alters the binding of fMLP and GM-CSF to their receptor(s), but may also alter signal transduction. Thus, aberrant glycosylation of CML granulocytes may reduce the binding of hematopoietic growth factors, which in turn may be responsible for the immature phenotype of CML granulocytes. PMID- 8220158 TI - A comparative analysis of alkylating agent and epipodophyllotoxin-related leukemias. AB - This review deals with the differences between leukemias--induced by alkylating agents as opposed to a "new form" of treatment related leukemia due to prior exposure to epipodophyllotoxins the latter having a short treatment--disease onset interval, absence of a MDS phase, a monocytic component and cytogenetic abnormalities involving the 11q23 band. The link between the existence of oncogenes or tumor suppressor genes located on the involved portion of chromosome 11 and the development of epipodophyllotoxin-related leukemia still needs to be examined. Alkylating agents--induced leukemias have a longer treatment--disease onset interval, have a prior myelodysplastic syndrome, and are most frequent myeloblastic or myelomonocytic in nature. Karyotype analysis reveals partial or complete deletion of chromosomes no. 5 or 7. This form of leukemia is highly resistant to treatment in the majority of cases. Some of the possible molecular mechanisms of leukemogenesis are discussed. PMID- 8220159 TI - Investigation of BCL-2 gene rearrangements in a United Kingdom series of low and high grade non-Hodgkin's lymphomas. AB - Rearrangements of the BCL-2 gene are thought to be the most frequent genetic changes that occur in non-Hodgkin's lymphomas (NHL), and are particularly associated with follicular low grade disease. Wide variations in the frequency of these rearrangements have, however, been reported in studies of NHL series from different parts of the world. We were therefore interested to determine the frequency of BCL-2 gene rearrangements in the different grades of NHL from a U.K. series. We have done this by using a combination of Southern blot hybridization and polymerase chain reaction (PCR) analysis. The frequencies of rearrangements in our series were 9/20 (45%) in low grade follicular NHL, 1/8 (12.5%) in low grade lymphocytic and 5/19 (26%) in high grade NHL. However, estimation of the high grade value was complicated by the fact that a number of the high grade samples in our series were from patients who had transformed from low grade follicular disease. If the patients were ranked on the basis of whether they had a history of low grade follicular disease then the frequency of BCL-2 rearrangement remained the same 13/29 (45%), but was only 1/10 (10%) in high grade NHL with no history of follicular disease. The former figure was intermediate between those reported for the USA and Japan series, but the latter high grade figure was the lowest reported from any series. The significance of BCL-2 rearrangements in the evolution of both low and high grade NHL is discussed. PMID- 8220160 TI - In vitro effect of rGM-CSF on proliferation and maturation of leukemic cells from patients with acute myelogenous leukemia. AB - We investigated the effect of rGM-CSF on the proliferation/differentiation balance of the leukemic cells maintained in liquid cultures during 7 days, from 16 patients with acute myelogenous leukemia (AML). Cell proliferation was measured by tritiated thymidine (3HT) incorporation, and by the plating efficiency (PE) observed after 7 days of culture. Differentiation was measured by the ability of cells to reduce nitroblue tetrazolium (NBT) and by the percentage of immature myeloid cells. After 7 days of culture without rGM-CSF, an increase of 3HT incorporation (p = 0.01 compared to control) was observed in 8 cases. In these patients, an absence of PE was noted in only one case. Among the 8 patients with decreased 3HT incorporation (p = 0.01 compared to control), 6 exhibited functional maturation (increase of % of NBT + cells, p = 0.01), and 4 showed no PE. Seven days exposure to 50 ng/ml rGM-CSF increased the leukemic cell proliferation in 9 cases, induced complete functional differentiation in 4, and enhanced the CFU-L recovery in 6 cases. These effects were mainly observed in the "proliferative" group, where 7 of the cases had an increase of 3H-T. However, two of the "non proliferative" cases were also stimulated by GM-CSF. An absence of proliferation was generally accompanied by functional maturation. PMID- 8220161 TI - Milestone and events in the early development of human gene therapy. PMID- 8220162 TI - Hunting for Huntington's disease. PMID- 8220163 TI - Genetics, insurance, and the ethics of genetic counseling. PMID- 8220164 TI - Genetics of astrocytic tumor progression. PMID- 8220165 TI - Molecular biology of Alzheimer's disease. PMID- 8220166 TI - Vasoactive intestinal peptide: its interactions with calmodulin and catalytic antibodies. PMID- 8220167 TI - Vasoactive intestinal peptide: involvement of calmodulin and catalytic antibodies. PMID- 8220168 TI - Vasoactive intestinal peptide: role of calmodulin and catalytic antibodies. AB - In the accompanying article Paul and Ebadi [1993 (Neurochem Int. 23, 197-214)] review recent observations that the neuropeptide vasoactive intestinal peptide (VIP) and the related peptide growth hormone releasing factor (GRF) bind to two novel protein molecules unrelated to their G-protein coupled receptors. VIP and GRF have been reported to bind with high affinity to calmodulin, leading to modulation of biological activities of the regulatory protein. VIP has also been reported to bind to autoantibodies isolated from both normal and asthmatic subjects. Several of these autoantibodies have been found to catalyze the hydrolysis of the native VIP molecule. The biological consequences of the binding of VIP and GRF to these macromolecular "receptors" are considered. PMID- 8220169 TI - Lipid peroxidation inhibits oleoyl-CoA: 1-acyl-sn-glycero-3-phosphocholine O acyltransferase in rat CNS axolemma-enriched fractions. AB - The effect of phospholipid peroxidation on the acylation of lysoPtdCho (lysophosphatidylcholine) by axolemma-enriched fraction prepared from rat brain stem was investigated. After two types of peroxidative treatments, the in vitro induction of malondialdehyde and conjugated dienes formation in axolemmal membranes correlated to a shift in the ratio of saturated/unsaturated fatty acids. By using an Fe2+ (20 microM)-ascorbate (0.25 mM) peroxidation system, the residual acyltransferase activity was 55% of the initial one. No change in Km value for either oleoyl-CoA or lysoPtdCho was found, whereas a loss of 24% in Vmax was observed. After 5 min preincubation with 150 mM t-BuOOH, 70% inactivation of the acylation reaction was observed. A near suppression of enzyme activity was reached with 400 mM. The apparent Km for oleoyl-CoA decreased sharply (from 6.6 microM in control preparations to 4.1 microM in t-BuOOH-treated membranes), indicating a 2-fold increase in the enzymatic affinity for this substrate. The apparent Km for lysoPtdCho increased markedly (from 1.56 microM in the control preparations to 5.88 microM in t-BuOOH-treated membranes) whereas a decrease of Vmax (from 1.65 to 0.80 nmol/min/mg protein) for the same substrate was observed. Significant enzyme inactivation (loss of 60% of initial activity) was seen when 10 mumol of photooxidized phospholipids were preincubated with axolemmal membranes. Significant dose-dependent enzyme inactivation was brought about by addition of 10-60 mumol of peroxidized PtdEtn/100 micrograms axolemmal protein. The percent enzyme inhibition by peroxidized PtdCho at equivalent amounts was lower than that by PtdEtn.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8220170 TI - Purification of peroxisomal fraction from rat brain. AB - A purification procedure to obtain peroxisomes (microperoxisomes) from the brain of suckling rats is reported. A P2 fraction, (crude light mitochondria) frozen and thawed seven times, was subfractionated yielding a P4 fraction, 4-fold enriched in catalase activity with respect to the cytoplasmic extract S1. The P4 fraction was used for further purification of peroxisomes by isopicnic centrifugation on Nycodenz gradient (1.10-1.20 g/ml). When the cerebellum was not included in the starting material, the equilibrium density of peroxisomes was 1.152-1.162 g/ml. In this case the overall yield of catalase in the most enriched fraction was 7% and its relative specific activity more than 50. When the cerebellum was included in the total homogenate, the equilibrium density shifted towards higher values (1.177 g/ml) and in this case the catalase relative specific activity in the peroxisomal enriched fraction was extremely high (> 100). The biochemical results, together with the electron microscope examination of the purified fractions, demonstrate that our procedure allows the best purification of brain peroxisomes so far obtained. The different equilibrium densities of peroxisomes observed in the two sets of experiments are interpreted in terms of size heterogeneity of these organelles in different brain portions and cell types. PMID- 8220172 TI - Nonsynaptic diffusion neurotransmission (NDN) in the brain. AB - The synapse has dominated the conceptual model of neurotransmission; other mechanisms, such as neuromodulation, have been considered to support and complement synaptic transmission. In this commentary, the conceptual framework considers synaptic transmission as one of several mechanisms of neurotransmission. One of these is nonsynaptic diffusion neurotransmission (NDN), which includes both the diffusion of neurotransmitters and other neuroactive substances through the extracellular fluid to reach extrasynaptic receptors, and the diffusion of substances such as nitric oxide through both the extracellular fluid and cellular membranes to act within the cell. The possible roles of NDN in mass, sustained functions such as mood, sleep and brain "tone", as well as in various other functions, such as in long term potentiation, at the retinal, lateral geniculate nucleus and visual cortex levels of the visual system, in recovery from brain damage and in neuropharmacology, are explored. PMID- 8220171 TI - Modulatory action of arachidonic acid on GABAA/chloride channel receptor function in adult and aged brain cortex membranes. AB - Effect of arachidonic acid on binding parameters of two binding sites on the GABAA receptor and on GABA activated Cl- uptake was investigated in synaptic plasma membrane and in synaptoneurosomes from brain cortex of adult (4-months old) and aged (27-months old) rats. The ligands used were [3H]muscimol, a GABA agonist and [35S]-t-butylbicyclophosphorothionate ([35S]TBPS), a convulsant that binds to the site near the chloride channel. Arachidonic acid increases significantly GABAA agonist binding and concomitantly decreases [35S]TBPS binding in a concentration dependent manner. The analysis of binding parameters in adult brain showed a significant decrease by AA of KD value for low but not for high affinity of [3H]muscimol binding. Concomitantly, AA enhances Bmax values for high affinity binding and has no effect on Bmax value for low affinity binding in synaptic plasma membrane (SPM) from adult brain. In synaptic plasma membrane from aged brain AA increases low and high affinity binding of agonist to GABAA receptor, modified significantly KD value by about 30 and 66%, respectively. On the other hand, AA significantly decreases of [35S]TBPS binding to chloride channel recognition site. Scatchard's analysis indicates that this inhibition results from a decrease of total number of binding sites. Moreover, the affinity of [35S]TBPS binding was increased (KD = 37.0 nM for AA-treated membrane, as compared to 69.3 nM KD in control membrane). GABA-dependent chloride uptake into synaptoneurosomes is also inhibited by AA in a concentration dependent manner in adult brain. In aged brain synaptoneurosomes AA has similar inhibitory effect on GABA-activated chloride uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8220173 TI - Naloxone receptor binding in gerbil striatum and hippocampus following transient cerebral ischemia. AB - Receptor autoradiographic and histological techniques were used to investigate sequential alteration of naloxone receptors in the gerbil brain 1 h-7 days after transient cerebral ischemia. Transient ischemia was induced for 10 min. [3H]Naloxone binding showed a transient elevation in the striatum 1 h after ischemia, whereas the hippocampus revealed no significant alteration in the binding. Thereafter, no conspicuous alteration in [3H]naloxone binding was seen in the striatum and hippocampus up to 24 h after ischemia. However, a significant elevation in [3H]naloxone binding was found in the hippocampal region 48 h after ischemia. In contrast, the striatum showed no significant alteration in [3H]naloxone binding. Seven days after ischemia, a severe reduction in [3H]naloxone binding was seen not only in the dorsolateral striatum and hippocampal CA3 pyramidal cell layer, where irreversible neuronal damage was found, but also in the histopathological intact dentate gyrus. However, the hippocampal CA1 sector which was most vulnerable to ischemia, revealed no conspicuous alteration in [3H]naloxone binding. These results demonstrate that alteration of naloxone receptors precedes ischemic neuronal damage to the striatum and hippocampus. They also suggest that the damage between striatum and hippocampus may be produced with different processes. PMID- 8220175 TI - Analysis of rapid calcium signals in synaptosomes. AB - A combination of the stopped-flow technology with dual channel spectrofluorometry of Ca(2+)-indicators was utilized for the measurement of rapid Ca(2+)-signals in rat cerebral cortical synaptosomes evoked by K(+)-depolarization. There was no observable contribution of Ca(2+)-ions from intracellular stores to the rise in [Ca2+]i. The kinetics of the fast increase in intracellular Ca2+ concentration was analysed in relation to the depolarization strength. The maximal increase in [Ca2+]i and the time course of Ca(2+)-channel inactivation were determined for depolarizations obtained by different extracellular K(+)-concentrations ([K+]o). An apparent threshold was observed at about 18 mM [K+]o; a maximal Ca(2+)-signal amplitude was estimated at about 40 mM [K+]o. Pharmacological properties of the involved Ca(2+)-channels were determined using selective Ca(2+)-channel blockers (Dihydropyridines, omega-Conotoxin, omega-Agatoxins); the results suggest that a P-type voltage-dependent Ca(2+)-channel is the relevant channel type, generating the evoked Ca(2+)-signals in rat cerebral cortical synaptosomes. PMID- 8220174 TI - Acute swim stress increases benzodiazepine receptors, but not GABAA or GABAB receptors, in the rat cerebral cortex. AB - We have examined the effects of swim stress on gamma-aminobutyric acidA (GABAA), GABAB and benzodiazepine (BZD) receptors in synaptic membranes from rat brain. Acute, but not repeated, stress increased the number of BZD receptors in the cerebral cortex. The stress manipulation did not change BZD receptors either in the hippocampus or cerebellum. Furthermore, both GABAA and GABAB receptors did not change in the cerebral cortex, hippocampus or cerebellum after acute and repeated stress. GABA-stimulated BZD binding was not changed following acute or repeated stress. These results suggest that cortical BZD receptors are closely related to responses to acute stress. PMID- 8220177 TI - Rapid steady-state analysis of blood-brain transfer of L-Trp in rat, with special reference to the plasma protein binding. AB - We estimated constants for the binding of tryptophan (Trp) to plasma proteins, and for the transfer of Trp from plasma to brain in rat. The measurements were made under conditions in which the plasma and brain concentrations of Trp were raised to new steady-states for at least 10 min before being measured. The concentration of other competing amino acids were also at a steady-state. The plasma Trp concentration was elevated by i.p. injection of different doses of L tryptophan methyl ester 60 min before the measurement of the plasma-brain transfer. We simultaneously measured blood flow with [14C]-butanol, and the brain tissue Trp uptake with [3H]Trp. The maximal velocity (Vmax), apparent half saturation Michaelis-Menten constant (Km(app)), and diffusion constant (PdS) for Trp transport from plasma into brain were found to be 7.0 +/- 2.1 nmol g-1 min-1, 36 +/- 17 microM, and 0.065 +/- 0.006 ml g-1 min-1, respectively. The maximum plasma protein binding (Bmax) and dissociation constant (KD) for Trp were estimated at 360 +/- 16 nmol/ml-plasma and 81 +/- 10 microM, respectively. We conclude that the plasma protein binding of Trp inhibits the blood-brain transfer in inverse proportion to the plasma free Trp concentration. PMID- 8220176 TI - Soluble serotonin and catecholamine binding proteins in the bovine adrenal medulla. AB - The soluble serotonin-binding proteins (SBP) present in the adrenal medulla and in chromaffin cells, are very similar to those reported for the bovine brain and retina. Binding of [3H]serotonin and [3H]dopamine to these SBP is increased by Fe2+ but not by Fe3+. At an optimal concentration of Fe2+ (0.1 mM) these proteins behave as a single class of non-cooperative sites for [3H]serotonin (Bmax = 124 +/- 28 pmol/mg protein, KD = 0.51 +/- 0.13 microM) and [3H]dopamine (Bmax = 685 +/- 118 pmol/mg protein, KD = 0.46 +/- 0.06 microM). Binding of [3H]dopamine is also increased by Cu2+ and Mn2+, but to a lesser extent than by Fe2+. Catecholamines are good competitors for [3H]serotonin binding (Ki = 0.31 microM for dopamine, 0.6 microM for adrenaline and 0.9 microM for noradrenaline). The serotonin binding proteins from adrenal medulla elute in the void volume of a Sephacryl 100 HR gel filtration column, reflecting aggregation, and migrate mainly with an apparent molecular weight of 45 kDa in native polyacrylamide gel electrophoresis experiments. Subcellular localization studies and release experiments suggest that SBP are not present in chromaffin granules, but in the cytosol of purified chromaffin cells. The present data suggest that these proteins must have other functions than storing monoamines in synaptic vesicles. PMID- 8220178 TI - Continuously infusing quinpirole decreases Ca2+/calmodulin-dependent phosphorylation in mouse striatum. AB - Continuously administering the D2 dopamine agonist quinpirole to mice for 6 days produces an initial stereotypy that is reduced by 2 h and is absent from 3 h to the 6 day duration of the infusion. In an attempt to determine the biochemical correlates for this down-regulation of stereotypic behavior, the effects of continuously administering quinpirole on a number of biochemical parameters were measured in mouse corpus striatum. After 6 days of infusion with quinpirole, the striata were analyzed for D1 and D2 dopamine receptors, for the activities of several protein phosphorylation reactions which are thought to be involved in receptor activity and for the levels of calmodulin-binding proteins. Quinpirole decreased the D2 receptors in striatum and produced a small but statistically non significant increase in D1 receptors, resulting in a significant increase in the ratio of D1 to D2 dopamine receptors. An examination of the effects of quinpirole on protein phosphorylation systems showed that the agonist failed to alter the activity of cyclic AMP-dependent protein kinase or protein kinase C but significantly decreased the Ca2+/calmodulin-dependent phosphorylation of striatal membranes. However, this decrease in Ca2+/calmodulin-dependent phosphorylation was not associated with changes in the levels of calmodulin-binding proteins. The results suggest that behavioral down-regulation following the continuous administration of a D2 dopamine agonist is associated with at least two biochemical events: a down-regulation of D2 dopamine receptors and a decrease of Ca2+/calmodulin-dependent phosphorylation of striatal membranes. PMID- 8220179 TI - Synthesis and evaluation of [125I]-(S)-iodozacopride, a high affinity radioligand for 5HT3 receptors. AB - We have developed a high specific activity radioiodinated ligand for the biochemical evaluation and autoradiographic localization of 5HT3 receptors in the brain. [125I]-(S)-iodozacopride was synthesized by radioiodination of deschloro (S)-zacopride using chloramine-T, and the product was purified by HPLC. The equilibrium kinetics and pharmacology of the binding of this radioligand were studied in homogenates of rat cerebral cortex, while the distribution of binding was examined by quantitative autoradiography. [125I]-(S)-iodozacopride bound to a single, saturable, specific binding site (Kd = 192 +/- 9 pM, Bmax = 1.2 +/- 0.2 fmol/mg protein). The binding had the pharmacological properties of a 5HT3 receptor, being potently inhibited by a variety of 5HT3 agonists and antagonists including (S)-zacopride (Ki = 0.032 nM), Quipazine (Ki = 0.45 nM), LY278584 (Ki = 0.5 nM), (1-m-chlorophenyl)-biguanide (Ki = 0.6 nM) and ICS 205-930 (Ki = 1.0 nM). Autoradiographic studies were undertaken by incubating sections with 400 pM [125I]-(S)-iodozacopride and exposing them to film for 3-7 days to obtain suitable autoradiograms. Specific binding of [125I]-(S)-iodozacopride was found at various amounts in a variety of brain regions. The highest levels of binding were found in the brainstem, principally the nucleus of the solitary tract with somewhat lower levels in the area postrema, substantia gelatinosa of the trigeminal nucleus and dorsal motor nucleus of the vagus. In the rat forebrain, moderate levels of specific binding were found in the glomerular layer of the olfactory bulb, anterior olfactory nucleus and various subnuclei of the amygdala. Lower levels of binding were seen in the superficial laminae of the parietal cerebral cortex and diffusely distributed throughout the hippocampal formation. In conclusion, [125I]-(S)-iodozacopride binds to a receptor site with the pharmacological properties and distribution that is consistent with the 5HT3 receptor. [125I]-(S)-iodozacopride represents a significant improvement in autoradiographic studies of the 5HT3 receptor by reducing the required exposure time for producing autoradiograms from the 3-6 months required for [3H]-labeled ligands to 3-7 days. PMID- 8220180 TI - Profile of prostaglandins induced by endothelin-1 in human brain capillary endothelium. AB - The vasoactive peptide, endothelin-1 (ET-1) has been implicated in the pathophysiology of various diseases. Recently, we have shown that human brain endothelial cells both secrete and express immunoreactive ET-1 high-affinity ETA receptors coupled to activation of phospholipase C (PLC). The present study demonstrates concentration-dependent stimulation of prostanoids [thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha), 6-keto prostaglandin F1 alpha (6 keto PGF1 alpha) prostaglandin E2 (PGE2), and prostaglandin D2 (PGD2)] production by ET-1 in capillary endothelial cells derived from human brain (HBCEC). The increase in the vasoconstrictive prostanoids TxA2 and PGF2 alpha temporally preceded that of the vasodilatory PGI2, PGE2 and PGD2, and was seen after 15 min of incubation with ET-1 (10 nM). Increased production of vasodilatory prostanoids was observed between 4-8 h of incubation, whereas normalization of both vasoconstrictive and vasodilatory prostaglandins occurred 24 h after addition of ET-1. Both ET-1-stimulated prostanoid and IP3 production were inhibited by BQ123, a specific antagonist of ETA receptors. ET-1-induced prostanoid secretion by HBCEC was also inhibited by dexamethasone (50 microM) and diminished by neomycin (50 microM) and verapamil (10 microM) but not by nifedipine. Phorbol myristate ester potentiated ET-1-stimulated prostanoid secretion, whereas it inhibited IP3 production. Data indicate that ET-1 activates phospholipase A2 (PLA2) and PLC in HBCEC by different intracellular mechanisms. The subsequently induced secretion of vasoactive prostanoids by HBCEC may contribute both qualitatively and temporally to the vasoactive actions of ET-1. PMID- 8220181 TI - Empirical aspects of strand displacement amplification. AB - The most attractive feature of SDA is its operation at a single temperature, which removes the need for instrumented temperature cycling as with PCR and the ligase chain reaction. Highly reproducible temperature profiles, over a large array of samples, can burden the accuracy and expense of an amplification technique. However, the expense of a temperature cycler is offset somewhat by the cost of additional enzymes used in isothermal techniques. In comparisons with isothermal, transcription-based techniques, SDA requires fewer enzymes and has a simpler mechanism. SDA may also be more robust than transcription-based processes because it is not susceptible to contaminating ribonuclease activity. This is generally more of a concern when using clinical samples. The most significant disadvantage of SDA is its inability to efficiently amplify long target sequences. Until this short-coming is eliminated, SDA will be assigned to the diagnostic laboratory along with the ligase chain reaction. Currently, SDA cannot compete with PCR in research applications such as the isolation of gene sequences. The second disadvantage of SDA is that it operates at relatively low (nonstringent) temperatures, which produces considerable background reactions. Consequently, SDA reaction products cannot be analyzed routinely by ethidium stained gel electrophoresis, as is used commonly with PCR, unless the target sample contains a large number of initial targets. PMID- 8220182 TI - Automated DNA profiling employing multiplex amplification of short tandem repeat loci. AB - We have employed automated fluorescence-based technology to detect amplified tri , tetra-, and pentanucleotide short tandem repeat (STR) loci electrophoresed on denaturing polyacrylamide sequencing gels. The system described incorporates an internal size standard in each sample, allowing the STR-PCR products to be sized automatically with a high degree of precision. By utilizing different fluorescent dye markers for loci that have overlapping allele size ranges, we have developed three multiplex STR systems containing a total of 14 different loci. These multiplex systems were then used to evaluate the usefulness of the 14 loci for the identification of individuals. Allele frequency data were collected from a minimum of 50 individuals from each of three different racial groups: Caucasians, Afro-Caribbeans, and Asians. Of the resulting 42 locus population sets, deviation from Hardy-Weinberg equilibria was detected in only the STR HUMCYARO3-Caucasian data. The probabilities of two unrelated individuals matching by chance (pM) at all 14 loci in the three multiplex reactions was < 1 x 10(14). The combination of multiplex STR-PCR and automatic fluorescence-based detection is thus a rapid and powerful technique for individual identification. PMID- 8220183 TI - Fluorescence-based RT PCR analysis: determination of the ratio of soluble to membrane-bound forms of Fc gamma RIIA transcripts in hematopoietic cell lines. AB - We have developed a fluorescence-based RT PCR assay for determination of the ratio of two alternatively spliced transcripts in different cell types. Fluorescence detection, by an automated DNA sequencer, allows enhanced sensitivity and ease of data processing. PCR products are fluorescently tagged using a dye-labeled oligonucleotide primer during the PCR reaction. Assay conditions were first defined so that fluorescence intensity of the PCR products was linear with respect to input RNA and exponential relative to PCR cycle number. Sensitivity and reproducibility of detection were evaluated with serial dilutions of RT PCR reactions. We have applied this assay to an analysis of the lineage-specific expression of two human Fc gamma RIIA transcripts, Fc gamma RIIa1 and Fc gamma RIIa2, in different hematopoietic cell lines. Previously, we noted that when standard RT PCR conditions are used with primers that bracket the TM exon, the pattern of expression of these transcripts as assessed by ethidium bromide staining of agarose gels varied in different hematopoietic cell lineages. Using the fluorescence-based RT PCR method, we now confirm our previous findings and quantitate transcript ratios (Fc gamma RIIa2/Fc gamma RIIa1) in several hematopoietic cell lines. The ratio varies from 0.70 (41% Fc gamma RIIa2) in the erythroleukemic cell line HEL, to 0.14 (12% Fc gamma RIIa2) in the monocytic cell line U937, to 0.07 (6% Fc gamma RIIa2) in the multipotential cell line K562. This fluorescent RT PCR method provides a general approach to quantitating mRNA levels and ratios of PCR products in other gene systems. PMID- 8220184 TI - Rapid PCR construction of a gene containing Lym-1 antibody variable regions. PMID- 8220185 TI - Quantitation of beta-actin-specific mRNA transcripts using xeno-competitive PCR. PMID- 8220186 TI - Detection of unknown gene mutations by multiplex single-strand conformation polymorphism (MSSCP). PMID- 8220187 TI - Detection of exceedingly low levels of HIV proviral DNA in multimillion peripheral blood mononuclear cells by PCR. PMID- 8220188 TI - Interference of PCR amplification by the polyamines, spermine and spermidine. PMID- 8220189 TI - A simple and rapid DNA microextraction method for plant, animal, and insect suitable for RAPD and other PCR analyses. PMID- 8220191 TI - Room-temperature-stable PCR reagents. PMID- 8220190 TI - A method for accurate amplification of polymorphic CA-repeat sequences. AB - Anomalous PCR products are often produced during the amplification of d(CA)n.d(TG)n sequences. Upon denaturing polyacrylamide gel electrophoresis, these products yield a ladder-like pattern that can complicate genotypic interpretation. We have developed two related techniques, referred to as two- and three-stage linear amplification (2-SLA and 3-SLA, respectively), which largely overcome this problem and yield readily interpretable banding patterns. PMID- 8220192 TI - A simple procedure for enhancing PCR specificity. PMID- 8220193 TI - History: its relevance to practice. PMID- 8220194 TI - Challenges for nursing research in an era dominated by health service reform and cost containment. AB - Many health care systems around the world are under reform, not least for reason of necessary cost containment. As one of the largest items of a health service budget, the costs of nursing services are attracting particular attention. This behooves the nursing profession, if only in its own interest, to accumulate convincing evidence of the cost-effectiveness of nursing. Nursing's research track record in the assessment of the costs, quality, and effectiveness of nursing is assessed in this paper and found to be generally weak. The complexity of such research is acknowledged; the need for research which will insure and demonstrate the highest quality of nursing at the lowest possible cost is presented as a key challenge for nurse researchers in the present era. PMID- 8220195 TI - The development of mothers' understanding of infant crying. AB - This study examines the development of mothers' understanding of their infants' crying. Semistructured tape-recorded interviews were conducted with 17 mothers at 6 weeks, 10 weeks, and 16 weeks postpartum. The mothers (9 primiparous, 8 multiparous) were chosen for their good health status and for their immediate support system. Two major themes were identified from the interviews. In general, it was found that as the mothers became more experienced, the understanding of the cry situation became more complete and soothing was more effective. The relation between crying and soothing became more differentiated, more cohesive, and more complete. The effect of experience on understanding was particularly dramatic in the case of multiparous mothers. Both health promotional and illness prevention programming are proposed as nursing care measures for mothers of crying infants. The important assumptions underlying each approach are delineated. PMID- 8220196 TI - Behavioral responses of family members during critical illness. AB - This articles describes the behavioral responses of adult family members to critical illness and how these responses change over the course of the hospitalization. A convenience sample of 52 family members of patients in intensive units completed the Iowa ICU Family Scale, a self-report tool measuring sleep, eating, activity, family role, and support behaviors. Scales were completed by family members each day during the first week and then weekly throughout the patient's ICU stay. Family members reported sleeping less with a poorer quality of sleep, less nutritional intake, an increased use of cigarettes, alcohol, and over-the-counter and prescription medications, and spending more time talking, visiting the patient, and waiting. Stress was highest at the time of the ICU admission, began to plateau at Day 6, and then dropped considerably by Day 28. These findings suggest that crisis intervention is important during the early phase of caring for critically ill patients and their family members. PMID- 8220197 TI - Effects of therapeutic touch on anxiety in the institutionalized elderly. AB - The purpose of this study was to determine the effects of therapeutic touch, a specific healing technique, on state anxiety in 105 institutionalized elderly. A double-blind, three-group experimental design was used. State anxiety was measured using the Spielberger State-Trait Anxiety Inventory. The anxiety level of subjects who received therapeutic touch in the form of a back rub was found to be significantly lower than the anxiety level of subjects who received a back rub without therapeutic touch. Results suggest that this noninvasive intervention has potential for enhancing the quality of life for this population. PMID- 8220198 TI - Time experience of selected institutionalized adult clients. AB - Time experiences of 25 selected institutionalized adult clients were studied using the Time Experience Scale. Subject selection criteria were age, ability to comprehend written and oral English, institutionalization, and willingness to participate in the study. The findings suggest that institutionalized adult clients experienced time moving faster as they get older. Meaning, referring to concerns about dying and "attention to death," was found to be more important than past orientation, suggesting that institutionalized older adult clients were concerned about their time experience, its meaning, and influence on death. Nursing interventions could be directed toward increasing meaningful and purposeful activities, such as planned reminiscence therapy and reorientation techniques. PMID- 8220199 TI - Dietary fiber nursing intervention: prevention of constipation in older adults. AB - Constipation is a major complaint of older adults. Approximately 30% of older adults use laxatives at least once weekly, and laxatives account for 1% of physician prescriptions in addition to approximately 700 over-the-counter preparations. This study evaluated the efficacy of a fiber and fluid nursing intervention on the maintenance of bowel movements and elimination aid withdrawal in residents of a long-term health care facility. The findings indicated that the number of bowel movements reached a peak at 3 months and returned to baseline values at the 6-month point while the use of both laxatives and stool softeners decreased significantly. Enema and suppository use was so infrequent at baseline and throughout the study that changes in these variables were statistically insignificant. The results demonstrate that a natural means of maintaining bowel movements using a fiber and fluid nursing intervention can significantly decrease the number of laxatives and stool softeners needed by residents of a long-term facility. PMID- 8220200 TI - Effects of guided imagery in patients with chronic bronchitis and emphysema. AB - Together, chronic bronchitis and emphysema (CBE) ranks as one of the top five leading health problems in the United States. Few nursing interventions have been tested that improve symptom management, functional status, and quality of life. This study tested the effects of guided imagery and maximal inspiratory muscle training (MITT) in a group of 10 males and 9 females, 56-75 years old, with moderate CBE. The research tested whether the independent variables, guided imagery and MITT, have significant independent and/or interaction effects on the dependent variables functional status, fatigue, dyspnea, depression, mastery, quality of life, perceived health status, and inspiratory muscle strength. Results showed that the psychologic intervention of guided imagery significantly improved subjects' perceived quality of life. The physiologic intervention of MITT could not be tolerated by subjects, which precluded testing the effects on the dependent variables. Application of study findings to clinical practice and the need for further research are discussed. PMID- 8220201 TI - [Combinations of short oligonucleotides with increase duplex formation stability as combined primers for sequencing]. PMID- 8220202 TI - [Two families of Drosophila MDG4 retrotransposons differ in the ability to form new copies of DNA in cultured Drosophila cells using a reverse transcription method]. PMID- 8220203 TI - [Expression in Escherichia coli of hybrid genes, containing sequences, coding for human adrenocorticotropic hormone]. PMID- 8220204 TI - [Projections of afferent sympathetic cardiac nerves in the cerebral cortex, thalamus, and their interaction with afferents of brachial plexus nerves]. PMID- 8220205 TI - [Analysis of disorders in development of the brain in the new Notch mutant of Drosophila melanogaster]. PMID- 8220206 TI - [Phenomenon of trehalose accumulation in wild strains of Saccharomyces cerevisiae and S. paradoxus]. PMID- 8220207 TI - [Interhemispheric asymmetry in perceiving linear dimensions at various distances]. PMID- 8220208 TI - [Ultralow doses of oxytocin change blood coagulation in humans]. PMID- 8220209 TI - [New data on the radionuclide level in the Barents Sea and in littoral area]. PMID- 8220210 TI - [Hybridologic analysis confirms the species specificity of Phodopus sungorus (Pallus, 1773) and Rhodopus campbelli (Thomas, 1905)]. PMID- 8220211 TI - [The concept of base genome and critical mass of eukaryotic chromosomes]. PMID- 8220212 TI - [Cloning the Bos taurus beta-lactoglobulin gene]. PMID- 8220213 TI - [A new principle of organizing sequences in a genome--long mirrored nucleotide sequences]. PMID- 8220214 TI - [The effect of spatial organization of zygote cytoplasm on cell differentiation processes in mouse embryogenesis]. PMID- 8220215 TI - [Transplantation of minced cardiac muscle in place of a removed limb in a newt]. PMID- 8220216 TI - [Phenomenon of "fluctuating hypertrophy" of the heart]. PMID- 8220217 TI - [Condensation of nucleosome fibrils at increased temperature]. PMID- 8220218 TI - [Amino acid sequence and catalytic properties of the Bacillus coagulans extracellular ribonuclease]. PMID- 8220219 TI - [Topography of distribution of beta-galactosidase gene activity, introduced using ballistic transfection, in developing mouse embryos]. PMID- 8220220 TI - [Patterns of (3H)-propranolol binding by beta-2-adrenoreceptors in rat erythrocytes]. PMID- 8220221 TI - Recent applications of flow cytometry in aquatic microbial ecology. AB - Microorganisms (unicellular algae, bacteria) constitute fundamental compartments of aquatic ecosystems because of their high concentrations and activities. The evaluation and understanding of their behavior and role raise different problems for which traditional methodologies are often inadequate, whether they refer to global or classical microscopic analyses. Flow cytometry (FCM) has been recently used to study microorganisms in aquatic environments. Although this technology is still applied on a limited scale in our field, a large number of works has been done showing that FCM seems to be a promising tool for aquatic microbial ecology. This paper summarizes, from the literature produced during the last decade and with original data obtained in our laboratory, the main questions related to the cell identification, the evaluation of cell viability, biomasses and productions and the measurements of bacterial and phytoplanktonic activities. The representatives of sampling and observation scales is also discussed within the framework of the FCM measurements. PMID- 8220222 TI - Application of flow cytometry to rapid microbial analysis in food and drinks industries. AB - In food and drinks industries, the time required for conventional tests can lead to substantial delays in product release to the market. Flow cytometry (FCM) has been used in conjunction with viability markers for rapid counting of yeast, mould and bacterial cells in food products. A single-parameter flow cytometer has proved applicable to the rapid detection of low numbers of microbial contaminants in finished products. The excellent correlation between FCM results and product quality shelf-life expiry date has allowed the establishment of realistic quality control criteria for rapid positive release of product. Used for the monitoring of microbial biomass during manufacturing processes, flow cytometry allowed a direct assessment of bacterial growth. The reproducibility of the results and the proven correlation with standard plate count method obtained in industrial conditions make FCM a good predictive method for product and process quality control. PMID- 8220223 TI - Image and flow cytometry: companion techniques for adherent and non-adherent cell analysis and sorting. AB - Flow cytometry (FMC) is an analytical and preparative technique whereas image analysis is only applied to cell analysis. Recently, image analysis has been adapted as a preparative method using a new technique: image cytometry for analysis and sorting (ICAS). FCM and ICAS are complementary. Flow cytometry allows rapid, quantitative and precise study of fluorescence and light scattering in a large number of cells in suspension, while ICAS analyses fewer cells (adherent cells or tissue) on the basis of fluorescence, morphology and size. ICAS can use these criteria to destroy unwanted cells and hence sort selected cells. ICAS can also be used for confocal microscopy and laser surgery. PMID- 8220224 TI - Cell cycle analysis by flow cytometry: principles and applications. AB - Numerous flow cytometric analyses are based on DNA content studies. We have considered firstly monoparametric cell cycle analyses, which only take DNA content into account, but are sometimes of limited interest. Then, we have presented multiparametric analyses, which can be used to improve cycle phase identification by taking simultaneously into account DNA and other cellular components, or by considering some events occurring during cell cycle. Finally, we have discussed monoparametric and multiparametric cell cycle analysis interest in various application fields, particularly in pharmacology, toxicology, tumoral pathology and higher plant system studies. PMID- 8220225 TI - Analysis and sorting of chromosomes by flow cytometry: new trends. AB - Flow cytogenetic is widely used since 1975, and essentially contributes to karyotype analysis and chromosome sorting. The principles of experimentation and its possibilities and limitations are now well known. Recently several new technologies have appeared. What attitude should the cytometrist adopt regarding PCR, microdissection of chromosomes, in situ hybridization, slit-scan flow cytometry or image analysis? PMID- 8220226 TI - A cytometric exercise in plant DNA histograms, with 2C values for 70 species. AB - An introduction is given to the literature concerning methods and objectives for cytometric DNA analysis of plant nuclei. This area has gained relevance with applications in plant breeding and seed production industries, where laboratories unfamiliar with cytometry are adopting the method. An extensive graphical guide to interpreting DNA histograms and their problems is given. Conversely, cytometry laboratories unfamiliar with plant sciences will find herein a guide, and references, to adapt their methods to plant material. A table of 2C values reassessed by flow cytometry for 70 plant species, plus the genome composition (GC%) in many instances, is also included. PMID- 8220227 TI - Flow cytometric analysis for reproductive biology. AB - Flow cytometric studies of spermatogenesis have been advanced by the need for: i) rapid, sensitive, objective and multiparameter measurements of reproductive effects due to environmental, occupational, and therapeutic exposure to toxicants; and ii) assessment of fertility potential of human and animal sperm. As a consequence, various flow cytometric techniques are already available to identify germ cell subpopulations undergoing both proliferative and maturative processes in normal and perturbed conditions. Significant improvements have been introduced in order to investigate the spermatogenic complex differentiation pathway and the apparent uniformity of mature sperm. Flow cytometry (FCM) has been applied to the measurement of both testis and sperm cells in a variety of species, including man. End points considered in toxicology studies are: altered testicular germ cell ratios, DNA and RNA content, increase of the coefficient of variation, induction of diploid elongated spermatids and diploid sperm, altered nuclear morphology, sperm cell viability, mitochondrial function and sperm chromatin structure. Precise DNA content measurements allow accurate analysis to determine the proportion of X- and Y-chromosome bearing sperm and sorting of these subpopulations for gender preselection. FCM technology has reached a maturation level that allows its inclusion in the list of available and routine methods for reproductive studies in human and animal populations. PMID- 8220228 TI - Clinical applications of flow cytometry in hematology and immunology. AB - Rapid developments in computer technology combined with new fluorescent dyes and monoclonal antibody production have led to the development of a powerful tool: flow cytometry. The techniques of flow cytometry can be applied in a wide clinical field, from routine tasks to research in immunology and hematology. The availability of automated instruments and standardized sample preparation methods have led to its daily clinical use, helping diagnosis, prognosis or monitoring therapy. Further advances will be made with the introduction of multi-parametric analysis ie quantification of antigen expression of cell surface antigens. PMID- 8220229 TI - Interlaboratory quality assessment of lymphocyte phenotyping. Etalonorme 1990 1992 surveys. AB - A 3-year interlaboratory proficiency testing for lymphocyte subset phenotyping was initiated as part of the Etalonorme national quality control program. Specimens consisted of fresh whole blood and of lyophilised mononuclear cells (Cytotrol Coulter). The number of participating laboratories was 62 in 1990, 99 in 1991 and 129 in 1992. Statistical analysis indicated that results of phenotyping, expressed as percentages of positive cells, are not related to reagents, instruments or differences in methodology (like, eg time and temperature of incubation). The highest dispersion was observed for total lymphocyte counts and was found to correlate with the type of calibration of the instrument. The coefficients of variation for different lymphocyte subsets were similar if phenotyping was performed on whole blood or lyophilised cells and varied inversely with the percentage of positive cells in each specimen. The consistency of the results indicated that they could serve as a basis for clinical decisions. PMID- 8220230 TI - Flow cytometry's contribution to the measurement of cell functions. AB - Flow cytometry has important advantages over conventional techniques. It is rapid, highly sensitive and allows multi-parametric analysis and cell sorting. Potential exists for the measurement of many cell functions by flow cytometry. The technique can be used to determine cell viability, intracellular calcium and pH, membrane potential, enzyme activities, membrane fluidity and endocytosis. Numerous examples are given on the applications of flow cytometry for cell functions measurements in the fundamental and biomedical fields. PMID- 8220231 TI - Recent advances of flow cytometry in fundamental and applied microbiology. AB - This review focuses on the recent applications of flow cytometry (FCM) in microbiological research (1987-mid 1992). It tries to give a scope of the important breakthroughs which occurred in this field during this period. The technical difficulties of microorganism analysis by flow cytometry is briefly appraised. The significance and the limits of the different microbial cell parameters attainable by flow analyses are systematically evaluated: light scatter for cell size and structure, fluorescence measurements for quantification of cellular components, microbial antigen detection and cell physiological activity estimation. Emphasis is given on the new technological advances which appeared in the last two years. The second part of the review is devoted to the analysis of the usefulness of flow cytometric approach in the different fields of microbiology: fundamental studies in microbial physiology, differentiation, microbial ecology and aquatic sciences, medical microbiology, parasitology, microbial pharmacology and biotechnology. PMID- 8220232 TI - Detrimental effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a mutagenic agent, on mitochondrial respiration among various rat tissues. AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is a potent mutagenic agent produced during thermal processing of meats. Since 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine has a similar structure to tetrahydroisoquinoline, a mitochondria toxic compound, we determined whether or not this compound shows detrimental effects on mitochondrial electron transport activities in various rat tissues. Administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 100 mg/kg twice a week for 4 weeks, decreased significantly the activity of complex I in mitochondrial electron transport chain of heart, diaphragm, and psoas major, while it did not affect the activities of complex I in the liver mitochondria. Concerning the activities of complexes II, III, and IV, no significant effects were observed irrespective of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine administration. Age-related deterioration of mitochondrial function seems to be a major contributor to age-related decline in cellular function. From our results, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine might act as an accelerator of age-related decline in mitochondrial function. PMID- 8220233 TI - Effects of alcohol abuse: studies on human erythrocyte susceptibility to lipid peroxidation. AB - The susceptibility to lipid peroxidation induced by an iron-ascorbate system was studied in human erythrocyte membranes (ghost), and measured as thiobarbituric acid reactive substances (TBARS) formed. The male and female subjects were 13 chronic alcoholic patients aged 34-54 who assumed 200-250 g/die of ethanol, and 12 healthy controls aged 23-46. In alcoholics ghost sensitivity to lipid peroxidation was significantly decreased compared with that of the controls. Peroxidation on lipids extracted from the ghosts of both control and alcoholic subjects confirmed an increased resistance to free radical damage of the erythrocyte membranes obtained from alcoholic patients, thus indicating that in alcoholic patients the lipid component is involved in the resistance to free radical damage of erythrocyte membranes. Lipid analysis revealed no significant difference in cholesterol and phospholipid content, nor in the phospholipid classes, of the two groups considered. Nevertheless the fatty acid composition of ghosts from the alcoholic subjects was significantly lower in docosahexaenoic acid content than in the controls, and it is with this in mind we propose the explanation of the results we obtained. PMID- 8220234 TI - Serum stimulation of UDP-glucose dehydrogenase activity in Swiss 3T3 fibroblasts. AB - A new HPLC assay was developed to measure UDP-glucose dehydrogenase (UDP-GDH) activity in crude homogenates of 3T3 fibroblasts. UDP-GDH activity is directly related to the proliferative activity of the cell culture: enzyme activity is highest in log phase cells and decreases as the culture approaches quiescence. Serum stimulation of quiescent 3T3 fibroblasts results in an increase in UDP-GDH activity that has two components that are differentially affected by inhibitors of protein synthesis. Following serum stimulation, changes in cellular UDP glucuronic acid concentrations mirror changes in UDP-GDH activity. UDP-xylose is a potent inhibitor of UDP-GDH but inhibitory concentrations of UDP-xylose could not be detected in cell extracts. PMID- 8220235 TI - Polygalacturonase isozymes from Botrytis cinerea grown on apple pectin. AB - Five isozymes (four acidic and one basic) of polygalacturonase were separated by chromatofocusing from the culture filtrate of Botrytis cinerea grown on apple pectin. The isozymes, designated as Polygalacturonase I to V, have isoelectric points of 9.7, 4.9, 4.6, 3.7, and 2.7, respectively, with Polygalacturonase III exhibiting the highest specific activity. Polygalacturonase I appeared to function as an endo-polygalacturonase while the other four isozymes act as exo polygalacturonases. The pH optima of the isozymes range from pH 4.5 to 5.5 with Polygalacturonase V being less sensitive to higher pH compared with the rest of the isozymes. PMID- 8220236 TI - Study on the translocation of chicken heart apocytochrome C with different unfolded states. AB - Chemically-prepared chicken heart apocytochrome c with different unfolded states could be obtained during the renaturation process. They exhibited distinct circular dichroism patterns designated as Apo C1 (random coiled), Apo C2 (less ordered) and Apo C3 (more ordered). This characteristic is unique to chicken heart apocytochrome c while compared with its counterparts from Candida krusei, tuna heart or horse heart and promises the emergence of much more detail of correlation of translocation with unfolded states of apocytochrome c. When chicken heart apocytochrome c was subjected to a translocation assay in vitro using trypsin-enclosed large unilamellar vesicles from soybean phospholipids, the ability of the protein to penetrate into the liposomes was found to follow the order of Apo C1 > Apo C2 > Apo C3. Conformational alterations of Apo C1, Apo C2 and Apo C3 in association with soybean phospholipid vesicles shown by circular dichroism measurement demonstrated that Apo C1 bound to phospholipids existed in a more loosely folded conformation than Apo C2 and Apo C3. We propose that a more flexible structure of apocytochrome c following the interaction with phospholipids is required for its efficient translocation across the bilayer. PMID- 8220237 TI - Association of erythrocyte glycophorin with protoporphyrin-IX derivatives: a fluorimetric study. AB - Based on demonstrations that protoporphyrin-IX and its metabolic derivatives bilirubin and hemin bind to the red cell membrane, their association with glycophorin A, the main transmembrane sialoglycoprotein, was assessed. No interaction between bilirubin and glycophorin could be demonstrated but both protoporphyrin-IX and hemin were found to bind to the protein. Interaction of protoporphyrin-IX and glycophorin was demonstrated by changes in both ligand and protein fluorescence characteristics in the presence of the other reactant. Binding of hemin, (Fe+3-protoporphyrin-IX) with glycophorin was revealed by quenching of the proteins' intrinsic fluorescence intensity by hemin and a shifted Soret absorption of hemin in the presence of glycophorin. The association constants of protoporphyrin-IX and hemin with glycophorin at 25 degrees C were calculated as 2.5 +/- 0.5 x 10(6)M-1 and 1.4 +/- 0.4 x 10(6)M-1 respectively. PMID- 8220238 TI - Pyridoxine is a precursor of the pyrimidine moiety of thiamin in Saccharomyces cerevisiae. AB - We studied the origin of the N-1 atom of the pyrimidine moiety of thiamin in a eucaryote, Saccharomyces cerevisiae. The competitive effects of 14N-compounds on the incorporation of 15N-NH4Cl into the pyrimidine moiety were examined. Amino acids, the bases of nucleic acids and glucosamine did not decrease 15N incorporation, but pyridoxine did. We conclude that the N-atom of pyridoxine is the origin of the N-1 atom of the pyrimidine of thiamin synthesized by S. cerevisiae. We also suggest that the N-atom of pyridoxine is derived from glutamine. PMID- 8220239 TI - Three forms of cellobiohydrolase I from Trichoderma reesei. AB - Three forms of cellobiohydrolase I (CBH I) (65, 58 and 54 kDa) were isolated to apparent homogeneity from culture filtrates of Trichoderma reesei. The N-terminal sequence of amino acid residues is the same for all of them. The 65 kDa CBH I (pI 4.1) is the intact protein which is fully active against small, soluble substrates and an insoluble substrate Avicel. The 58 kDa CBH I (pI 3.8) and 54 kDa CBH I (pI 3.6) are two truncated forms of the intact CBH I, which are fully active against small, soluble substrates, but have decreased adsorption on and activity against Avicel. Limited proteolysis of the 65 kDa and 58 kDa CBH I by papain yields the same core protein (pI 3.6, 54 kDa). It appears that there are mainly two different specific proteolytic cleavage points in the intact CBH I, one the site for a papain-like protease action cutting at the hinge area (54 kDa CBH I) and the other in the B block (58 kDa CBH I). PMID- 8220240 TI - Transport of mitoribosomal proteins, YmL13 and MRP7, into isolated mitochondria of Saccharomyces cerevisiae. AB - Two mitochondrial ribosomal proteins, YmL13 and MRP7, of the yeast Saccharomyces cerevisiae and their derivatives were synthesized in vitro and their transport into isolated yeast mitochondria was examined. Both proteins were transported into yeast mitochondria in an energy-dependent manner. MRP7 protein was transported even when its N-terminal presequence was deleted, and the N-terminal presequence alone was not capable of transporting a fused passenger protein, Chinese hamster DHFR. YmL13 protein, on the other hand, was not transported without its N-terminal presequence, and its presequence was capable of transporting Chinese hamster DHFR into mitochondria. Thus, MRP7 appears to possess a transport signal in its mature part, while YmL13 possesses a signal only in its N-terminal presequence. PMID- 8220241 TI - Human breast milk contains procathepsin D--detection by specific antibodies. AB - The presence of the zymogen of cathepsin D in human milk was detected using antibodies specific for the proenzyme and by the proteolytic activity at low pH. The antibodies were raised against a synthetic propeptide of human cathepsin D and were tested using immunoprecipitations and western blots of samples from different breast cancer cell lines as well as cytosol fractions of human breast cancer tissues. In all experiments these antibodies recognized specifically procathepsin D. Procathepsin D from human milk was partially activated at low pH. The activity was monitored using hemoglobin 14C proteolytic assay, and it was abolished by pepstatin A--a specific inhibitor of aspartic proteinases. Western blots did not reveal presence of cathepsin B or cathepsin H. These data indicate specific secretion of cathepsin D in human breast milk. PMID- 8220242 TI - Changes in skeletal muscle, heart and liver mitochondrial electron transport activities in rats and dogs of various ages. AB - We determined skeletal muscle, heart and liver mitochondrial electron transport activities in rats and dogs of various ages. In the skeletal muscle mitochondria, decrease in the activity of complex I was observed in rats aged 28 weeks, and further reduction of the activity was observed in rats aged 55 weeks. A significant decrease in complex IV activity was observed in rats aged 55 weeks. No significant reduction in complex II and III activities were observed in rats aged up to 100 weeks. Significant decreases in complex I and IV activities were observed in heart muscles of rats aged 100 weeks, while no significant changes in the activity of complex I in liver mitochondria were observed in rats aged up to 100 weeks. Similar results were obtained in dogs, i.e., the activity of complex I was the most susceptible to aging among the activities of complexes; and skeletal muscle mitochondria were the most susceptible to aging among the tissues. From our results, involvement of mitochondria in the development of age-related decline in cellular function is especially emphasized in post mitotic cells, and age-associated mitochondrial functional changes are stressed in mitochondrial complexes which contain mitochondrial DNA-encoded subunits. PMID- 8220243 TI - Preparation of highly purified human myelin oligodendrocyte glycoprotein in quantities sufficient for encephalitogenicity and immunogenicity studies. AB - Myelin oligodendrocyte glycoprotein, (MOG), a quantitatively minor central nervous system (CNS) myelin component, is a candidate target antigen for autoimmune-mediated demyelination. It is a highly hydrophobic protein present in very small amounts in CNS tissue and thereby difficult to purify. Our aim was to devise a purification procedure that would yield sufficient quantities of highly purified MOG to subsequently test its potential encephalitogenic activity, as well as investigate the humoral and cell-mediated responses to this antigen in naturally occurring and experimentally induced autoimmune demyelinating diseases. MOG was purified from human CNS white matter using immunoaffinity chromatography, a procedure that gave a final yield of MOG corresponding to 0.02% total white matter protein. The final product, which migrated as two bands of molecular weight 28 kDa and 58 kDa, was highly pure as shown also by specific reactivity with monoclonal anti-MOG antibodies on immunoblots in the absence of any detectable reactivity with antibodies specific for myelin basic protein, proteolipid protein and myelin-associated glycoprotein. Partial amino acid sequence was obtained from both MOG bands separated by SDS-PAGE and electroblotted onto PVDF. The sequence of the first 17 N-terminal amino acids had approximately 55% homology with the reported rat MOG sequence deduced from the cloned cDNA sequence; small internal sequences obtained showed also very high homology. Our purified MOG preparations have been used to investigate T cell response to MOG by peripheral blood lymphocytes of multiple sclerosis patients and to induce a relapsing remitting demyelinating disease in Lewis rats. PMID- 8220244 TI - The effect of protein kinase C modulators on endogenous protein phosphorylation in primate kidney. AB - The effects of modulators of protein kinase C on protein phosphorylation were studied in primate kidney. Phosphorylation of specific proteins, investigated using electrophoresis and autoradiography, indicated that in the absence of modulators eight major proteins were phosphorylated in membrane of baboon kidney; modulators enhanced a possible endogenous substrate of 41.8 +/- 2.3 kDa. In cytosol, eight major proteins were phosphorylated in the absence of modulators; a band of mass 110.4 +/- 13.8 kDa was enhanced with modulators added. Similar results were found in human kidney cytosol. PMID- 8220245 TI - The collision of cotranscribing E. coli RNA polymerases studied in vitro. AB - The collision of cotranscribing E. coli ternary complexes was brought about in vitro by forcing the first "leading" complex to stall before first template C, due to the absence of CTP, and then permitting initiation of a second "following" complex. Following collision, the transcript of the leading complex was increased in length by as much as 7 nt., despite the absence of CTP, but did not dissociate. Upon addition of CTP, the leading complex aborted at exactly the positions requiring incorporation of the next Cs', the following complex continued transcription. The observations point to the importance of linking appropriate promoter efficiency with transcriptional pausing times, and the role of transcriptional collisions in termination events. PMID- 8220246 TI - Transcription pausing signal detected by sense/antisense transcription. AB - We studied elongation pausing during transcription in vitro on both the sense and the antisense strands of a given gene fragment(5' end of the bla gene of Tn3). The average transcription rate on the sense strand was much lower than that of the antisense strand, and several pauses observed on the former have no detectable antisense partner. A pausing signal was identified, associated with an (AT)6 sequence, in the vicinity of a strong pause on the sense strand and the sole detected pause on the antisense strand. Mutation of this sequence strongly reduced, by a common factor, pausing times at both sites. PMID- 8220247 TI - Preparation of membrane vesicles from kidney cortex lysosomes using amino acid methyl ester. AB - A procedure for the preparation of intact membrane vesicles from kidney cortex lysosomes is reported. Highly purified preparations of lysosomes were isolated from rat and buffalo kidney cortex by Percoll density gradient centrifugation. The lysosomal membrane vesicles were prepared by osmotic rupture of the organelle with glutamate dimethyl ester. The integrity of the vesicles was demonstrated by their capacity to hold K+ and maintain H+ gradients. PMID- 8220248 TI - Blood testosterone levels are correlated with beta-N-acetylhexosaminidase activity in human caput epididymis. AB - beta-N-acetylhexosaminidase exhibits a relatively high activity in human epididymis. Its isoenzymatic profile and immunological properties led us to conclude that the increased activity was not due to the expression of an isoform unrelated to the HEX A and B present in other human tissues. Measurement of enzyme levels in the three distinct epididymal regions revealed that in any given sample, activity was higher in the caput than in the corpus or cauda. Moreover, we found a striking correlation between beta-HEX activity in the caput region and concentrations of blood testosterone, suggesting a possible involvement of the hormone in modulating enzyme expression. Since the caput epididymis plays a role in the maturation of sperm cells, our data may be an indication that beta-HEX activity in the caput has a physiological relevance in human epididymis functions. PMID- 8220249 TI - Alginate may accumulate in cystic fibrosis lung because the enzymatic and free radical capacities of phagocytic cells are inadequate for its degradation. AB - We sought an explanation for the accumulation, and apparent poor degradation by alveolar phagocytes, of alginate in cystic fibrosis lung. A crude intracellular lyase preparation extracted from Klebsiella pneumoniae was able to degrade seaweed alginic acid as well as forms purified from Pseudomonas aeruginosa bacteria from Cystic Fibrosis (CF) patient lungs. This was by a beta-eliminative mechanism, as detected by an increase in the 232nm absorbance and activity was enhanced by deacetylation of the Pseudomonas aeruginosa alginates. Conditioned media or cell lysates from unstimulated or triggered phagocytic cells (including resident mouse peritoneal macrophages and the human macrophage cell line U937) had no effect in the same system. Free radicals generated by chemical systems or by gamma irradiation of water degraded alginate. Depolymerisation by free radicals, as detected by viscosity determinations and polyacrylamide gel electrophoresis, generated a wide range of fragment sizes. In contrast, mouse peritoneal macrophages or human polymorphonuclear neutrophils stimulated to generate free radicals had no significant effect on alginate. Under the conditions of our experiments, phagocytic cells representative of the CF lung are not able to degrade Pseudomonas aeruginosa alginate. This may explain the gross accumulation of alginate in CF lung. PMID- 8220250 TI - Appearance of different diabetic symptoms after streptozocin administration: a comparison study. AB - The purpose of the present study was to compare the time required to develop each of the following diabetic symptoms after the streptozocin administration (60 mg/kg, iv) in rats: hyperglycaemia, glycosuria, polyuria, polydipsia, polyphagia, and body weight reduction. The data showed that hyperglycaemia, glycosuria, polyuria and polydipsia were significantly increased in 24 hours after the streptozocin administration; however, there was a delay of 3 days before a significant reduction of body weight was detected, and the food intake was not significantly increased until 7 days after the streptozocin administration. PMID- 8220251 TI - Altered levels of histone H1(0) and DNA topoisomerase activity in the liver of the tumour-bearing rat. AB - Walker 256 carcinoma cells were injected subcutaneously into the dorsal region of rats. After 9 days of tumour growth increases were observed in liver mass and DNA content and in the incorporation of [3H]-thymidine into liver DNA. These changes were accompanied by a fall in the H1(0) fraction of liver histones and rises in both DNA topoisomerase I and II activities. PMID- 8220252 TI - H2O2-induced damage to beef heart mitochondria F0F1 ATP synthase complex: differential sensitivity of the F1 and F0 moieties. AB - Exposure of purified mitochondrial F0F1 ATP synthase to H2O2 resulted in a marked inhibition of the ATPase activity, irrespective of the purification procedure used and of the incorporation of the enzyme complex into phospholipid vesicles. The inactivation appeared consequent to oxidative modifications of the F1 moiety, whereas damage to the F0 sector, leading to low enzyme activity through impaired binding with F1, seemed not to occur. In fact, when H2O2-inactivated complex was deprived of F1, no loss of the capacity of the F0 sector thus obtained to properly reassemble with untreated purified F1 was apparent, because the resulting enzyme complex showed full activity and oligomycin sensitivity. On the contrary, the exposure of the isolated components F1 or F0 to H2O2, followed by reassembly with untreated F0 and F1 respectively, resulted in both cases in lower catalytic activity of the reconstituted complexes, whereas low oligomycin sensitivity was exhibited only in the case of F0 treatment, suggesting the inactivation in this case as due to oxidative modifications leading to impaired binding with F1. PMID- 8220253 TI - Adenosine affects the f-met-leu-phe induced changes in cytosolic Ca2+ and in membrane potential of human granulocytes. AB - Indo 1 acetoxymethyl ester and 3,3-dipentyloxacarbocyanine iodide have been used to investigate the effect of adenosine on the changes in cytosolic Ca2+ concentration and in membrane potential of human granulocytes activated by the chemotactic tripeptide f-met-leu-phe. Adenosine does not significantly affect negative (hyperpolarizing) potential changes as well as calcium accumulation in cytosol, whereas both the amplitude of the depolarization phase and the relaxation time for restoring the initial intracellular calcium level are reduced. PMID- 8220254 TI - S-adenosylhomocysteine hydrolase from Acinetobacter calcoaceticus: purification and partial characterization. AB - S-adenosylhomocysteine hydrolase (SAHase) was purified to homogeneity from the Gram negative strain Acinetobacter calcoaceticus 501. The molecular weight of the native enzyme, estimated by gel permeation, was about 288 KDa, while sodium dodecyl sulfate polyacrylamide gel electrophoresis yielded a relative molecular mass of 48 KDa. The determination of the coenzyme content gave 4 mol of NAD+ and 2 mol of NADH per mol of enzyme. The isoelectric point of native SAHase was at pH 5.1. When assayed in the hydrolytic direction, the Km for S-adenosylhomocysteine and the Vmax of the enzyme for this substrate were 84 microM and 357 mumol/min/mg, respectively; in the synthetic direction, instead, the Km for adenosine and the corresponding Vmax value were 1.6 microM and 37 mumol/min/mg. Substrate analogs were tested for their ability to act as inhibitors and inactivators of the enzyme. Among these compounds, 9-beta-arabinofuranosyl adenine (Ara A) appeared as the most powerful competitive inhibitor (Ki = 18 microM) as well as the strongest time-dependent inactivator. The common feature of all the assayed analogs was the presence of the adenine ring in their molecular structure. It can thus concluded that the presence of the adenine moiety is an essential element in substrate and/or inhibitor interaction with this bacterial enzyme. PMID- 8220255 TI - Modulation of LH secretion by progesterone and estradiol after naloxone injection in the median eminence. AB - To evaluate whether the median eminence (ME) is a site of action of opioids on gonadotropin secretion, and to determinate the role of estradiol (E) and progesterone (P) in modifying these secretion in response to naloxone, we injected naloxone (1, 2.5 and 5 micrograms) into the ME in ovariectomized rats treated with estradiol benzoate (OVX+E) or ovariectomized rats treated with estradiol benzoate plus progesterone (OVX+E+P), and measured LH and FSH serum levels 10 and 30 min postinjection. Naloxone injection at doses of 2.5 and 5 micrograms significantly increased serum LH levels in OVX+E animals 10 and 30 min postinjection, whereas naloxone injection at all doses in OVX+E+P rats did not have any significant effect on LH secretion 10 and 30 min postinjection, when compared with values obtained in controls injected with saline. The injection of naloxone into the ME did not modify FSH secretion. We conclude that naloxone, acting within the ME, can elicit LH release in OVX+E rats, while it abolishes this effect in OVX+E+P rats. PMID- 8220256 TI - Electrophoretic mobility changes of oxidized human low density lipoprotein measured by laser Doppler electrophoresis. AB - Laser Doppler Electrophoresis was used to detect changes in the surface charge of low density lipoprotein populations exposed to oxidative stress. Before oxidative stress, low density lipoprotein suspensions exhibited homogenous populations of net negative charge but after exposure to hydroxyl and superoxide radicals, peroxyl radicals, or by Cu2+ generated oxidants they exhibited Laser Doppler Electrophoresis changes. The major population of low density lipoprotein became more negatively charged, in agreement with agarose gel electrophoresis. However, Laser Doppler Electrophoresis detected greater heterogeneity of low density lipoprotein, compared to agarose gel electrophoresis. Partially oxidized low density lipoprotein exhibited a less negatively charged subpopulation of particles compared to control samples. This has not been reported previously. Hence, Laser Doppler Electrophoresis is a sensitive method for detecting the appearance of subpopulations of differing surface charge density in oxidatively modified low density lipoprotein. beta-carotene protected low density lipoprotein against oxidative modification even when endogenous vitamin E levels are low. Vitamin E-deficient low density lipoprotein pretreated with beta-carotene exhibited a more narrow negative population when oxidized with peroxyl radicals, compared to control. Native low density lipoprotein pretreated with a mixture of all-trans- and cis-beta-carotene was also protected. PMID- 8220257 TI - Alteration in 5'-nucleotidase activities and composition of liver and brain microsomes of developing rats fed different dietary fats. AB - Four groups of male weanling rats were fed during three months, diets different in the nature of fats and the activity of 5' nucleotidase and fatty acid composition of brain and liver microsomes were studied. Group A were fed a standard commercial diet, group B a fat free-diet and group C and D a fat free diet, containing respectively 10% of peanut-rapeseed oil and 10% of salmon oil. In brain and liver microsomes, 5'-nucleotidase activity increased throughout the development for all diets (except for the fat-free diet). Slight differences were found in rats fed the peanut-rapeseed oil diet compared to controls estimated at the same time. However, in animals fed the fish-oil diet, 5' nucleotidase had the highest activity in both brain and liver microsomes. Marked changes occurred in the fatty acid patterns of brain and liver microsomes among the various groups. The greatest alterations were found in the liver microsomes. In brain and liver microsomal membranes the fat-free diet induced an increase in monounsaturated fatty acids, an synthesis of eicosatrienoic acid, and a decrease in (n-6) and (n 3) polyunsaturated fatty acids. Animals fed a peanut-rapeseed oil and control diet showed similar fatty acid patterns in liver and brain microsomes. However, when rats were fed a fish-oil diet, the liver microsomal membranes were highly enriched in eicosapentaenoic and docosahexaenoic acids, and simultaneously there was a decrease in arachidonic acid. These results suggest that manipulation of the lipid environment influences 5'-nucleotidase activity by the interaction of the enzyme with specific membrane lipids. PMID- 8220258 TI - Surface charge modifications do not affect the hydrolytic activity of membrane bound pyrophosphatase of Rhodospirillum rubrum. AB - The surface charge of the membrane of chromatophores of Rhodospirillum rubrum was modified by two methods: fusion of liposomes with the membrane of the chromatophore by changing the pH and by incubating chromatophores in the presence of cationic or anionic detergents. The hydrolytic activity of membrane-bound pyrophosphatase, on surface charge modified chromatophores, did not change the Km of the enzyme for its substrate (Mg-PPi2-) nor the activation effect of free Mg2+ on the hydrolytic activity. This membrane enzyme is not regulated by surface charge. PMID- 8220259 TI - Metabolic conversion of phosphatidylserine via phosphatidylethanolamine into phosphatidylcholine in rat brain. AB - Exogenous, liposomal [14C]phosphatidylserine, and that synthesized from [14C]serine, were very slowly metabolized in cortex and hippocampus slices of rat brain; phosphatidylethanolamine (PE) formed from phosphatidylserine (PS) was not methylated to phosphatidylcholine (PC) for up to 6 hours of incubation. Among homogenates prepared from 7 separate brain regions, the cerebellum showed the highest, and the striatum and pons the lowest rate of PS synthesis and its further decarboxylation to PE; in all of these regions the stepwise methylation of PE to PC was very low. Isolated microsomal and mitochondrial fractions of whole rat brain, mixed together and incubated with [14C]serine and S adenosylmethionine, displayed a high level of newly synthesized mitochondrial PE, and a low level of methylated PC in the microsomes. Moreover, PE formed in brain microsomes by the base exchange reaction was converted into PC in an insignificant range. These data show a limited activity for sequential methylation of PE into PC in rat brain, and suggest that it is probably not caused by the slow movement of mitochondrial PE. PMID- 8220260 TI - Carboxyatractylate inhibits the potentiating effect of lipophylic cation TPP+ on uncoupling activity of fatty acid. AB - The effect of TPP+ on the fatty acid or FCCP-induced uncoupling in rat heart mitochondria was studied. It was found that (a) TPP+ increases the stimulation of oxygen consumption by palmitic acid or FCCP in the presence of oligomycin, (b) TPP+ greatly enhances the palmitic acid or FCCP-induced delta psi decrease. Both effects of TPP+ were strongly suppressed by carboxyatractylate in the case of palmitate but were not in the case of FCCP. The role of ATP/ADP-antiporter in the TPP+ and palmitic acid effects is discussed. PMID- 8220261 TI - Expression and RNA dependent RNA polymerase activity of birnavirus VP1 protein in bacteria and yeast. AB - Birnaviruses typically encode a polyprotein that is the precursor to the structural proteins of the virus and a protein of rare abundance, VP1, that is the putative dsRNA replicase and/or transcriptase. We have reconstructed the VP1 gene of IBDV from a library of cDNA clones and expressed the gene in Escherichia coli and in Saccharomyces cerevisiae. We could not detect an RNA polymerase activity associated with E. coli-derived VP1, and neither could we promote the yeast-derived VP1 to replicate exogenous IBDV dsRNA. However, the yeast-derived VP1 was shown to have an actinomycin-insensitive RNA polymerase activity that can recognise an endogenous template in S. cerevisiae. Our work suggests that further studies on birnavirus replication may be best addressed using an S. cerevisiae expression system. PMID- 8220262 TI - A broad-specific alkaline DNase from rat brain with a putative role in DNA excision repair. AB - An alkaline endodeoxyribonuclease from rat brain has been purified to near homogeneity. The purified enzyme showed a M.Wt. of 54 Kd on SDS-PAGE and does not require metal ion for activity and thus differs from classical DNase I. No preference towards any particular form of calf thymus DNA (native, denatured, undamaged and damaged by exposure to UV, H2O2 and OsO4 and depurination) was noticed. However, with supercoiled pBR 322 plasmid DNA as substrate, higher activity was exhibited towards UV irradiated and depurinated forms. It is suggested that this DNase may be a 'housekeeping' enzyme to detect any conformational distortion in DNA and initiate excision repair. PMID- 8220263 TI - Transfer of phospholipids and cholesterol from triglyceride-rich emulsions to HDL in rats treated with alloxan, propylthiouracil or ethanol. AB - 1. The transfer of lipids that constitute the surface of lipoprotein particles, phospholipids and unesterified cholesterol, from chylomicrons and VLDL to other lipoproteins, mainly HDL, was examined. 2. Emulsions known to mimic the metabolism of chylomicrons labeled with [3H]-phosphatidylcholine, [14C] cholesterol or [3H]-triolein were injected through a cannula implanted into the carotid artery of male Wistar rats weighing 280-350 g. Plasma clearance of the radioactively labeled emulsion lipid constituents and transfer of surface lipids from the emulsions to native HDL and LDL were measured in plasma samples collected at 2-min intervals during 10 min. 3. The transfer was measured in rats with alloxan-induced diabetes (single intraperitoneal dose, 140 mg/kg body weight) or with propylthiouracil-induced hypothyroidism (0.1% v/v in drinking water for 30 days), or given ethanol (20% in drinking water) for a period of 30 days, and in control rats. 4. The entry of emulsion phospholipids into the HDL fraction was not affected by the different treatments (controls: 9.3 +/- 0.6% of injected radioactivity, N = 8; diabetes: 12.5 +/- 2.4%, N = 9; hypothyroidism: 10.9 +/- 0.9%, N = 13; ethanol: 7.8 +/- 0.9%, N = 5). However, phospholipid transfer to the LDL fraction was increased in diabetes (10.0 +/- 2.3%) and hypothyroidism (12.1 +/- 1.3%) compared to controls (6.7 +/- 0.9%). Transfer of unesterified cholesterol from the emulsions to LDL and HDL was increased in both diabetic and hypothyroid rats (controls, LDL: 1.6 +/- 0.6%, HDL: 2.5 +/- 0.6, N = 5; diabetes, LDL: 5.3 +/- 1.2, HDL: 8.4 +/- 2.1 N = 5; hypothyroidism, LDL: 4.0 +/- 0.6, HDL: 3.6 +/- 0.4, N = 8). In ethanol-treated rats, transfer of surface lipids was similar to controls. PMID- 8220264 TI - Purification and characterization of endopeptidase H2, a kinin inactivating serine proteinase (kininase) from human urine. AB - 1. A kinin-inactivating chymotrypsin-like serine-endopeptidase was purified 202 fold from human urine by DEAE-cellulose chromatography, gel filtration, DEAE/HPLC chromatography and affinity chromatography. It hydrolyzed bradykinin at the Phe5 Ser6 peptide bond at a rate of 1.090 mumol min-1 mg protein-1 at pH 8.0 and 37 degrees C. The molecular weight of this endopeptidase H2, estimated by SDS polyacrylamide gel electrophoresis and by gel filtration, was 60 kDa, and its optimum pH for bradykinin hydrolysis was near 8.5. 2. Bradykinin inactivating activity was inhibited 100% by the serine-proteinase inhibitor PMFS (1 mM) and the chymotrypsin inhibitor TPCK (5 mM). Reagents such as 2-mercaptoethanol (3 mM) and pOH-mercuribenzoate (3 mM) inhibited the enzyme by 100% and 67%, respectively. 3. Endopeptidase H2 hydrolyzes the Phe-Ser bond of peptides related to bradykinin and its activity appears to be limited to peptide chains of < or = 18 amino acid residues since it does not hydrolyze BAM 22, peptide E or kininogen. 4. The molecular size and inhibition profile suggested that endopeptidase H2 differs from the serine-proteinases previously described in rat liver, rat hepatic endothelium, rat and rabbit brain. 5. The physiological role of endopeptidase H2 may be a link between the kinin and neuropeptide systems in the control of water-electrolyte balance. PMID- 8220265 TI - High dietary carbohydrate and pancreatic lesion. AB - The ability of high dietary carbohydrate to induce acute pancreatitis was investigated in groups of 16, 21-day and 15-month old rats fed different carbohydrate diets for 30 days. Significantly increased levels of serum amylase (2-fold), phospholipids (50%), phosphorus (2-fold), and lipoperoxides (8-fold) were observed in 15-month old rats fed a high-carbohydrate diet, compared to rats fed a diet with normal carbohydrate levels, indicating peroxidation of membrane lipids which caused final cell death and pancreatic lesion. Serum Cu-Zn superoxide dismutase activity was not altered. Daily administration of bovine Cu Zn superoxide dismutase conjugated with polyethylene glycol prevented the serum level alterations and pancreatic lesions, indicating that the superoxide radical has a role in dietary carbohydrate-induced acute pancreatitis. No biochemical changes were observed in rats in which treatment was initiated on the 21st day of life indicating that this is an age-related lesion. PMID- 8220266 TI - Heterogeneity of left ventricular perfusion during pulmonary edema and microembolism treated with positive end-expiratory pressure and norepinephrine. AB - Regional left ventricular myocardial blood flow was studied in an experimental model of pulmonary edema and microembolization (PEM) ventilated with positive end expiratory pressure (PEEP). The analysis was based on a 3-dimensional extension of the autocorrelation function used to assess the spatial correlation (rspat) of myocardial perfusion. Experiments were performed on 8 premedicated, anesthetized and mechanically ventilated dogs. PEM was induced with oleic acid (0.01 mg/kg) and glass beads. Successive PEEP values of 10, 15 and 20 cm H2O (P20) were applied and norepinephrine (NE, 0.2-1.0 microgram min-1 kg-1) was administered after P20. Regional perfusion was measured with radioactive microspheres. The left ventricle (LV) was dissected into 256 samples. rspat was computed as the correlation of regional perfusions of samples p units apart in the apex-to-base, endo-epicardial and angular directions. Analysis was performed after anesthesia and instrumentation (control, C), P20 and NE. Control values of rspat were around 50% in the apex-to-base and angular directions and the sign was inverted in the endo-epicardial direction. A reduction of rspat to values close to zero was observed in all directions for P20 and NE. This is the typical pattern of independent distribution. Thus, the results indicate that, under the experimental conditions used, there is some degree of neighborhood dependence of regional LV myocardial blood flow. This dependence is not observed under PEM, mechanical ventilation with PEEP and NE. PMID- 8220267 TI - Anti-PGL1 levels in leprosy patients and their contacts. AB - 1. We determined the anti-PGL1 levels of 402 individuals from the Ribeirao Preto region since the phenolic glycolipid (PGL1) is a specific Mycobacterium leprae antigen. This group consisted of 47 leprosy patients (26 with the lepromatous form, 16 with the tuberculoid form and 5 with the borderline form), 12 tuberculosis patients, 19 leprosy contacts, and 324 healthy blood donors from the Hemocenter of the University Hospital, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo. Anti-PGL1 levels were detected by ELISA. 2. Anti-PGL1 levels were normal in patients with tuberculoid and borderline leprosy, in tuberculosis patients and in almost all of the healthy blood donors. Patients with untreated lepromatous leprosy had elevated anti-PGL1 levels while most patients under treatment (9/16) had normal anti-PGL1 levels. Only 3% of blood donors (10/324) had elevated anti-PGL1 levels, but when these individuals were submitted to clinical and bacilloscopic examination no signs of disease were found. To complete the clinical investigation, these 10 subjects were submitted to the Mitsuda reaction which was negative in 3 of them. All of these 10 subjects are being monitored, since they may be at risk to develop leprosy. 3. On the basis of the present data, it seems that ELISA is a potentially important assay for the detection and chemotherapy of subclinical leprosy, permitting the control of epidemic centers of the disease. PMID- 8220268 TI - Effect of a persistent inflammatory process on experimental heterotopic ossification. The influence of macrophages. AB - 1. We investigated the effect of a persistent carrageenin- or nystatin-induced inflammatory reaction on heterotopic ossification produced by the subcutaneous implant of a demineralized bone matrix in female Swiss mice (25 to 35 g). 2. Subcutaneous carrageenin injection (0.3 ml of a 2% solution in saline) into mice induced an inflammatory reaction characterized by a mature granuloma predominantly of macrophages containing particles of the irritant in their cytoplasm and which remained unchanged until the end of the experiment (40th day). 3. Subcutaneous nystatin inoculation (30,000 IU in 0.3 ml saline) induced an inflammatory reaction consisting initially of macrophages (4th day) but later turning into an epithelioid granuloma (7th day) consisting predominantly of epithelioid cells and which was present up to the 21st day when it was gradually replaced by adipocytes up to the 30th day. 4. An intramuscular implant of demineralized bone matrix (DBM, approximately 10 mg) induced the formation of cartilage and bone tissue and of hemopoietic bone marrow (heterotopic ossification) in 100% of the control animals (N = 5). An intramuscular DBM implant in animals that received carrageenin (N = 19) or nystatin (N = 21) induced heterotopic ossification in 100 and 57% (P < 0.01) of the animals, respectively. 5. The response to a dorsal subcutaneous DBM implant was essentially negative in control animals (N = 5), whereas implants performed near the site injected with carrageenin (N = 28) or nystatin (N = 31) produced a response in 71 (P < 0.01) and 36% (P < 0.01) of the animals, respectively. A DBM implant into the contralateral (control) dorsal subcutaneous tissue of the same animals that received carrageenin (N = 25) or nystatin (N = 29) resulted in heterotopic ossification in 64 (P < 0.01) and 7% of the animals, respectively. 6. The results suggest that the macrophages present in the mature granuloma induced by carrageenin somehow favored the development of metaplastic plates after subcutaneous DBM implant and that this effect may be systemic since the same response was observed in contralateral subcutaneous tissue. PMID- 8220269 TI - The elevated T maze, a new experimental model of anxiety and memory: effect of diazepam. AB - In rats placed in a T maze consisting of an enclosed arm at right angles with two open arms elevated 50 cm above the ground, ip doses of 2 and 4 mg/kg diazepam (DZP) abolished the delay of withdrawal from the enclosed arm towards the open arms, measured by retesting in the presence of the drug soon after training, as well as by further retesting 72 h later, in the absence of the drug. Therefore, DZP had both anxiolytic and amnestic effects on this inhibitory avoidance task. In contrast, DZP did not affect the latency of withdrawal from one of the open arms towards the closed arm on the first day. Moreover, the latency of this escape response similarly decreased in all treatment groups in the retest performed 72 h later, indicating that memory of this task was resistant to DZP. These results support the view that the anxiolytic and amnestic effects of benzodiazepines are closely related, and suggest that this new elevated T maze model may be useful for simultaneous measurement of drug effects on anxiety and memory. PMID- 8220270 TI - Effects of a single administration of buspirone on catalepsy, yawning and stereotypy in rats. AB - In the present study, the effects of a single administration of buspirone (0.1, 0.3, 1.0, and 3.0 mg/kg sc-30 min before testing) on three dopamine-related behaviors were evaluated in 4-month old male Wistar rats (7-10 animals per group). Buspirone decreased haloperidol (2.0 mg/kg ip)-induced catalepsy in a dose-dependent manner (from 7.30 to 5.09 1n of s compared to the untreated control group). Apomorphine (0.06 mg/kg sc)-induced yawning was also dose dependently reduced (from 26.7 to 0.9 yawns in 30 min) and so was apomorphine (1.0 mg/kg sc)-induced stereotypy (from 32.9 to 5.9, sum of scores). The present results indicate that buspirone presents unique pharmacological effects related to dopaminergic transmission not only in biochemical but also in behavioral terms. PMID- 8220271 TI - Partial characterization of an ANF/urodilatin-like substance released from perfused rabbit kidney under hypoxia. AB - An ANF-like material was detected by radioimmunoassay in the isolated perfused rabbit kidney. The production of ANF-like material after 90 min of perfusion under hypoxia was 3000 pg/ml vs 500 pg/ml under normoxia or control conditions. This material is partially inactivated by heat treatment at 100 degrees C for 5 min and is absorbed on a SEP-PAK column (C18, Waters) but, unlike ANF, cannot be recovered from the column. On Sephadex G25 chromatography, elution in water yielded two active fractions, one corresponding to the solvent front and the second obtained after one column volume. Four fractions with biological activity were eluted with water from Sephacryl 200. Several fractions were tested on rabbit aorta preconstricted with 1 microM phenylephrine, without removal of endothelial cells. Treatment of T84 cells in culture by the crude material promoted a dose-related increase (1:2, 1:5, 1:10) of the generation of cyclic GMP. In contrast to our material, ANF (atriopeptin III, 1 microM-10 fM) failed to activate guanylate cyclase in T84 cells, while the heat-stable E. coli enterotoxin (STa) significantly increased cyclic GMP levels at the dose of 5 microM. We propose that a new ANF/urodilatin/ST-like material was generated by the hypoxic kidney under perfusion, which we name FNS (Factor Natriureticus Similis). PMID- 8220272 TI - Effects of Phoneutria nigriventer venom on rabbit vascular smooth muscle. AB - 1. The effects of Phneutria nigriventer venom (PNV) on rabbit vascular smooth muscle have been investigated. De-endothelialized vascular strips were superfused in a cascade system with oxygenated (95% O2 + 5% CO2) Krebs solution at 37 degrees C. 2. Phoneutria nigriventer venom (0.3-30 micrograms) produced dose dependent and short-lived contractions of both venous (cava, mesenteric and jugular veins) and arterial (pulmonary and mesenteric arteries) tissues. 3. Methysergide (5.0 microM) did not significantly affect PNV-induced contractions in venous tissues (cava and mesenteric veins) or pulmonary artery, indicating that serotonin is not involved in the contraction. This was confirmed when PNV was dialyzed (24-48 h) since the contracting activity was still observed on the above tissues. In addition, the spasmogenic activity induced by dialyzed PNV was greatly reduced by incubating the venom with trypsin. 4. Neither tetrodotoxin (3.0 microM) nor phenoxybenzamine (0.05 microM) significantly affected PNV induced contractions, suggesting that voltage-dependent sodium channel activation or endogenous catecholamine release from autonomic nerve endings on the vascular walls do not play a role in the response to PNV. 5. Our results demonstrate that PNV contains non-dialyzable components, probably peptides, that are responsible for the contractile activity on rabbit veins and pulmonary artery strips. PMID- 8220273 TI - Absence of genotoxic activity of beta-myrcene in the in vivo cytogenetic bone marrow assay. AB - beta-Myrcene (MYR, 7-methyl-3-methylene-1,6 octadiene) is a peripheral analgesic substance and one of the major constituents of lemongrass oil (Cymbopogon citratus, Stapf), a plant widely used in Brazilian folk medicine. In the present study the genotoxicity of MYR was evaluated in vivo using the rat bone marrow cytogenetic assay. Male and female Wistar rats weighing 250 g (223 to 286 g) and 178 g (168 to 186 g), respectively, were used. Two or four rats of either sex were treated orally with MYR (0.1, 0.5 and 1.0 g/kg po), corn oil (negative control) and cyclophosphamide 30 mg/kg ip (positive control). Animals were sacrificed and bone marrow cells were harvested 24 and 48 h after MYR administration. The mitotic index and the frequency of chromosome aberrations were evaluated. Fifty metaphase cells were examined per animal. A dose related increase in mitotic index was observed 24-h after MYR administration. No evidence of MYR-induced clastogenicity was observed under the experimental conditions of this in vivo assay. The present results and previous negative findings of in vitro mutagenicity tests strongly indicate that MYR is not a genotoxic substance. PMID- 8220274 TI - Effect of cicletanine on the progression of chronic renal failure in rats. AB - 1. The effects of chronically administered cicletanine (CICL), an antihypertensive and prostacyclin stimulating agent, on glomerular hemodynamics were evaluated after 30 (CRF-30) or 60 (CRF-60) days of chronic renal failure (CRF) induced by 5/6 nephrectomy in Munich-Wistar rats. 2. CICL administration (3 mg kg-1 day-1, N = 5) for 60 days did not modify glomerular hemodynamics of normal rats (control group). The CRF-60 group (N = 6) presented a significant increase in mean arterial pressure (MAP) compared with control (122 +/- 7 vs 98 +/- 2 mmHg, P < 0.05), which was attenuated by CICL (113 +/- 7 vs 122 +/- 7 mmHg). 3. Hyperfiltration and hyperperfusion were observed in both CRF groups after 30 (N = 5) but not after 60 days of CRF, 73.9 +/- 6.3 and 48.2 +/- 3.2 vs 36.8 +/- 2.6 nl/min for SNGFR and 200 +/- 17 and 147 +/- 8 vs 112 +/- 8 nl/min for QA in CRF-30, CRF-60 vs control group, respectively. However, glomerular hypertension was demonstrable for both CRF groups only after 60 days. CICL treatment starting 7 days prior to nephrectomy reduced the transcapillary hydraulic pressure difference (delta P) in both groups, 36 +/- 3 vs 30 +/- 2 mmHg (30 days) and 41 +/- 4 vs 34 +/- 2 (60 days), but did not significantly modify arteriolar resistances or glomerular hemodynamics, suggesting that the reduction in MAP in response to CICL may have been responsible for the decrease in delta P. CICL administration did not prevent the proteinuria or glomerular sclerosis associated with CRF. 4. The results suggest that the administration of CICL for 30 (N = 4) to 60 days (N = 7) was sufficient to prevent systemic hypertension associated with CRF but not to reduce the additional glomerular hemodynamic factors that participate in the progression of CRF. PMID- 8220275 TI - Reliable identification of click-evoked otoacoustic emissions using signal processing techniques. AB - As neonatal hearing screening programmes based on click-evolved otoacoustic emissions (CEOAEs) become more common, there is a need for automatic scoring methods to classify responses systematically. Such methods must guard rigorously against errors that would pass a baby who would otherwise fail and be referred for further diagnostic testing. Preliminary analysis of a wide range of CEOAE waveform characteristics from adult and neonatal ears suggested that the most reliable measure on which to base an automatic method was the cross-correlation coefficient between replicate non-linear components. Further analysis of recordings from 2049 ears of 1102 neonates in neonatal intensive care units indicated that a cross-correlation coefficient greater than 0.5 was an appropriate criterion to distinguish a pass from a fail, with the following two provisos. The waveforms should be high-pass filtered to remove random low frequency components before calculating the cross-correlation coefficient. The cross-correlation coefficient should relate to the time period from 6-16 ms after click onset. Using this method, 90% of recordings were automatically classified in agreement with a proven method of visual scoring. Only one ear without evidence of otoacoustic emission was passed by the automatic scoring method. PMID- 8220276 TI - Click-evoked otoacoustic emissions: new techniques and applications. AB - There are practical, clinical circumstances in which a decrease in test time for evoked otoacoustic emissions would be of economic or practical value. In addition, there are circumstances in which it is desirable to obtain more diagnostic information from the evoked emission. This preliminary report concerns predominantly one of these aspects but considers both of them. It is not possible to reduce the test time by simply increasing the stimulation rate because responses and stimuli will overlap and give rise to contaminated responses. However, these limitations can be overcome if a maximum length sequence of clicks is used. These sequences of clicks and silences enable responses of a duration greater than the time between stimuli to be recorded and deconvolved to produce an uncontaminated response. Conventional recordings at stimulus rates of 33/s and 50/s have been taken together with maximum length sequence recordings at rates up to 840/s and the waveforms correlate very well. Although the emission shows some adaptation at the highest stimulation rate this does not prevent a significant reduction in test time. PMID- 8220277 TI - Changes in 2f1-f2 distortion product otoacoustic emissions following alterations of cochlear metabolism. AB - This paper summarizes the results obtained from investigations in which distortion product otoacoustic emissions (DPOAEs) were studied together with other cochlear physiological parameters. The cochlear metabolism was subjected to three different experimental conditions: guinea pigs were either submitted to hypoxia, to an intra-cochlear perfusion of ouabain or to an intra-cochlear perfusion of naloxone. The data show that DPOAEs remain affected for a certain time after the metabolic perturbations were removed. The comparison of the behaviour of DPOAEs and of other cochlear parameters gives good indications on the way these different experimental procedures affect the functioning of the cochlea during and after their application. PMID- 8220278 TI - Some effects of tonal fatiguing on spontaneous and distortion-product otoacoustic emissions. AB - Auditory fatiguing can be considered a suitable test to assess some cochlear mechanisms and diseases otherwise not easily detectable. Since spontaneous otoacoustic emissions (SOAEs) originate from active sources within the cochlea they show sensitive and early vulnerability to noise, displaying informative time courses after overstimulation in the short (0-6 s) and in the long term (1-10 min) depending on the frequency of the fatiguing stimulus. Distortion product otoacoustic emissions too, in subjects with SOAEs, show interesting modifications after pure-tone exposure, detectable either on distortion product audiograms or in the growth functions. The modifications take place within a period of 5-7 minutes and strongly depend on the frequency of the fatiguing stimulus and on the closeness between SOAE and distortion product place. The data suggest that not only the interaction place between f1 and f2 has to be considered from a biomechanical and clinical point of view, but also the specific distortion product place on the cochlear partition. PMID- 8220279 TI - Evoked otoacoustic emissions in the study of adult sensorineural hearing loss. AB - In the present report the applicability of evoked otoacoustic emissions (EOAEs) in the clinical field for studying adult sensorineural hearing loss is discussed. Three topics are considered: (1) EOAEs replacing a testing procedure, (2) EOAEs integrating into the test battery thus validating the diagnostic outcome, (3) EOAEs implementing new diagnostic possibilities. The authors conclude that: (a) EOAEs could only be applied to replace pure-tone audiometry for assessing functional deafness, (b) EOAEs are a useful diagnostic tool complementing the audiological test battery, (c) EOAEs are a unique method that studies the efferent auditory pathways. It is suggested that EOAEs should be applied as a routine audiological test for adult sensorineural hearing loss not only in cases with a well-defined diagnostic profile, but also in those cases with a less clear diagnostic pattern, in order to collect more data and possibly gain better knowledge about the pathophysiology of the inner ear. PMID- 8220280 TI - Preliminary results and considerations in hearing screening of newborns based on otoacoustic emissions. AB - Many factors may determine the success of a screening programme based on the presence of evoked otoacoustic emissions (EOAEs), including age at test, stimulus used, examiner experience and method of data evaluation. This short report summarizes our experience based on pilot trials of a screen in the whole population of newborns using EOAEs. Optimal test time is when babies are at least 24 h old. Meticulous training of examiners and ultimately automatic evaluation of recordings is essential. Based on visual evaluation of responses to click stimuli at peak-equivalent sound pressure levels of 72.5 and 60.5 dB, 95.5% of babies passed the screen on at least one ear. However, we could only identify an EOAE in 81% of the waveforms for the 60.5 dB stimulus, and only 73% of the non-linear components derived by combining responses to the two stimuli contained an identifiable EOAE. At the present time, examination of both linear and non-linear components is indicated. PMID- 8220281 TI - The Munich screening programme in neonates. AB - For development, it is necessary to stimulate the auditory pathway during the first weeks of life. This knowledge and improved techniques for the treatment of young children with hearing loss make early detection even more important, otherwise developmental disabilities inevitably occur. The method of transient evoked otoacoustic emissions is the most useful test for neonatal screening and has the following advantages: emissions are quickly measured (i.e. within a few minutes), the measurements can be performed in the hospital nursery by trained volunteer examiners, the test produces the same results in awake, anaesthetized, sedated, and sleeping patients, and the existence of TEOAEs excludes with very high probability a peripheral hearing loss which may influence the development of speech. A prerequisite of a successful evaluation with crying and moving neonates is an apparatus with two specific rejection thresholds; one for time, the second for amplitude. Additionally, the probe has to be robust, but also small both to minimize its weight and to fit comfortably within the diameter of the neonatal ear canal. PMID- 8220282 TI - Using transient evoked otoacoustic emissions for neonatal hearing screening. AB - The Rhode Island Hearing Assessment Project was developed to determine the feasibility of establishing a valid cost-effective method of screening newborn hearing through a universal early identification programme. In a sample of 1850 infants, sensorineural hearing loss was identified in 11 infants using transient evoked otoacoustic emissions (TEOAEs). A second sample of 1451 infants showed similar trends in hearing loss identification. TEOAE was shown to have significant potential as a newborn screening tool when used in a carefully designed hospital-based early identification programme. PMID- 8220283 TI - Use of otoacoustic emissions to explore the medial olivocochlear system in humans. AB - The association between contralateral stimulation and otoacoustic emissions makes it possible to study the medial olivocochlear system in humans. Characterization of this functional exploration and clinical applications are discussed. PMID- 8220284 TI - Possible roles of outer hair cell d.c. movements in the cochlea. AB - Outer hair cells are expected to change the position of the cochlear partition in response to sound stimulation. This may contribute to the extended dynamic range of the cochlea. This paper explores the possible underlying mechanisms and the consequences for models of cochlear function of such position changes. PMID- 8220285 TI - Spontaneous cellular vibrations in the guinea-pig temporal-bone preparation. AB - Mechanical vibrations of Hensen cells were measured with a laser-heterodyne interferometer in the guinea-pig temporal-bone preparation without the application of an external acoustic stimulus. Smoothed periodograms (spectral density estimates v. frequency) were constructed from the velocity v. time waveforms recorded from individual cells. Several peaks were seen in the periodograms at levels as high as 10 dB above the noise floor, indicating the presence of spontaneous vibrations. The frequencies at which the peaks were located differed in different preparations, indicating that the observed peaks were not caused by the presence of ambient noise or ambient vibrations. Furthermore, vibrations were seen only in fresh preparations. The tuning curves of cells from which spontaneous vibrations were measured (determined by applying an external stimulus to the ear) had single principal peaks. Several peaks in the periodogram were found to be located within the principal-peak region of the tuning curve. The spontaneous response does not arise from noise filtered through the tuning curve which would have a single peak. We propose that these spontaneous vibrations originate at the outer hair cells and are the source of spontaneous otoacoustic emissions in the ear. PMID- 8220286 TI - Clinical monitoring using otoacoustic emissions. AB - Damaging influences to the cochlea are a leading cause of sensorineural hearing loss. Examples include acute or chronic noise exposure and cochleotoxic drugs such as aminoglycosides. Typically, once damage has occurred, the cochlea cannot recover. Therefore, prevention is critical. If damaging influences cannot be avoided, then secondary prevention or early detection of cochlear hearing loss becomes important. Ideally, methods for the detection of cochlear damage should be as specific and as sensitive as possible. Otoacoustic emissions satisfy these criteria and offer a means of testing aspects of cochlear function in a non invasive and objective way. Evoked otoacoustic emissions measured either after transient stimuli or during two-tone stimulation (distortion-product otoacoustic emissions) are the types most commonly used for clinical purposes. They are stable over time within individual ears and their repeatability has been established under conditions of clinical testing using commercial equipment. Thus, they are well suited as an effective means of monitoring subtle changes in cochlear status. The possibility of making non-invasive repeated measures of cochlear function has led to the widespread use of otoacoustic emissions in animal experiments. Influences of development, anoxia, anaesthesia, noise, and drugs have been monitored. Preliminary studies in humans demonstrate that cochlear damage due to ototoxic drugs such as aminoglycosides or cisplatin and due to noise exposure can be detected using otoacoustic emissions. Comparison of such results to those available using pure-tone audiometry indicates a greater sensitivity of otoacoustic emissions for detecting early cochlear damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8220287 TI - Otoacoustic emissions and the categorization of cochlear and retro-cochlear lesions. AB - There are only some cochlear and retro-cochlear lesions that could be detected using a simple measurement of otoacoustic emissions. A simple description of the various lesions that lead to hearing loss and disruption of emissions is presented, a basis for categorizing cochlear and retro-cochlear lesions is discussed, and the types of clinical symptoms likely to be associated with each type of lesion are outlined. PMID- 8220288 TI - Non-linearities of click-evoked otoacoustic emissions and the derived non-linear technique. AB - Averaged click-evoked and derived non-linear responses have been measured in normal ears to assess similarities and differences between the results obtained with the two methods. Computation of the input-output curves of click-evoked otoacoustic emissions with a short-time procedure reveals time-varying properties and the presence of saturation phenomena affecting, to various degrees, the linear content of emissions. Present preliminary results provide some guidelines towards the assessment of the relative role of the two techniques in otoacoustic emission testing. PMID- 8220289 TI - Revision of the surveillance case definition for AIDS in Canada. PMID- 8220290 TI - Paralytic polio in an adult female following OPV vaccination of her infant. PMID- 8220291 TI - Neisseria meningitidis with reduced susceptibility to penicillin isolated from blood culture--Quebec. PMID- 8220292 TI - The current global situation of the HIV/AIDS pandemic. PMID- 8220293 TI - Pertussis consensus conference. PMID- 8220294 TI - Canadian Consensus Conference on Influenza. PMID- 8220295 TI - 1993 Canadian recommendations for the prevention and treatment of malaria among international travellers. Committee to Advise on Tropical Medicine and Travel (CATMAT) PMID- 8220296 TI - Where are the immunotoxins in the clinic? PMID- 8220297 TI - Vitamin E in extrapyramidal disorders. AB - In this article the effect of vitamin E on two extrapyramidal disorders, tardive dyskinesia and Parkinson's disease, is reviewed. After a brief description of the symptoms, the current hypotheses for the pathogenesis of these diseases are described. A summary of the clinical research that has been done to establish the effectiveness of vitamin E is given. In tardive dyskinesia four clinical trials (double-blind, placebo-controlled) showed improvement in the symptoms with vitamin E in doses of up to 1,600 IU/day. Preliminary studies concerning Parkinson's disease suggested that vitamin E (2,000 IU/day) probably cannot prevent the development of the disease. It was suggested that vitamin E is able to slow the progression of the illness. The results from a large double-blind, placebo-controlled clinical trial, however, did not show any beneficial effect of vitamin E in Parkinson's disease. PMID- 8220298 TI - Aminoglycoside monitoring in the once- or twice-daily era. The Dutch situation considered. AB - The results of an inquiry among Dutch hospital pharmacists on the monitoring of aminoglycosides are presented and the relevance of monitoring is discussed. The vast majority of Dutch hospitals (47 out of 65) use aminoglycosides in a twice daily dosage regimen, whereas 12 hospitals use a once-daily dose. The timing of peak level sampling is usually 30 min after the end of an intravenous infusion of 20-30 min. Mean 'therapeutic' peak levels of gentamicin were 7-13 mg/l in the once-daily group, 6.4-9.6 mg/l in the twice-daily group and 5-9 mg/l in the small thrice-daily group. Little or no evidence has been published to substantiate a real therapeutic range for aminoglycosides, concerning a relationship between peak or trough levels of aminoglycosides and clinical efficacy, ototoxicity and nephrotoxicity. All studies have been performed with the conventional thrice daily regimen. No therapeutic range can be defined yet for once-daily or twice daily aminoglycosides. The monitoring of aminoglycosides may be helpful to reduce the variability in serum levels after a standard dose. PMID- 8220299 TI - Pharmacy personnel and fever: a study on perception, self-care and information to customers. AB - To study the fever perception and self-care of pharmacy personnel as well as the information given to customers about the management of fever problems, a random sample of 152 Norwegian pharmacists and 150 pharmacy technicians were interviewed, in 1989, by a national opinion poll company. One-third thought that body temperatures between 39.0 degrees C and 40.5 degrees C could be life threatening. Of all respondents 24% (33% of technicians, 16% of pharmacists) assumed body temperatures to be rising when sweating accompanied fever. In cases of common cold or influenza accompanied by fever 56% of the personnel would use antipyretics. 7% Of the staff (14% of technicians, 1% of pharmacists) believed penicillin to be effective against viral infections. Antipyretic drug preferences were consistent, but a wide range of perceptions was revealed, in particular with respect to start of antipyretic therapy and seeking medical care for children. Undergraduate and postgraduate education of pharmacy personnel should aim more at satisfying the demand for information of the general public and focus more on the symptomatic treatment of fever and minor illness in general. Pharmacists in charge have a special responsibility in counselling their assistants. PMID- 8220300 TI - General practitioners and fever: a study on perception, self-care and advice to patients. AB - To investigate their perception of fever problems, self-care and information given to patients, a random sample of 100 Norwegian general practitioners were interviewed in 1989-1990 by telephone. More than two-thirds of the general practitioners would define fever as a body temperature above 38.0 degrees C. One third would wait with antipyretic drug therapy for children until the temperature was above 39.5 degrees C. When dealing with fever in their own children, one third would not follow their own recommendations to parents with febrile children. 43% Had not discussed guidelines for the management of febrile patients with their receptionists. Only 7% had discussed such guidelines with the local pharmacists. Lack of consistency in the information given to patients may result in confusing advice. General practitioners, their receptionists and the local pharmacists should discuss and define guidelines for fever management and information to patients and parents. These should include information about antipyretic therapy and consultation behaviour. PMID- 8220301 TI - Probenecid inhibits the renal clearance and renal glucuronidation of nalidixic acid. A pilot experiment. AB - The aim of this pilot study was to demonstrate the possible inhibitory effect of probenecid on the renal glucuronidation and on the renal clearance of nalidixic acid in a human volunteer. Under acidic urine conditions, hardly any nalidixic acid is excreted unchanged (0.2%). It is excreted as acyl glucuronide (53.4%), 7 hydroxymethylnalidixic acid (10.0%), the latter's acyl glucuronide 30.9%, and 7 carboxynalidixic acid (4.2%). Under probenecid co-medication the renal glucuronidation of nalidixic acid is reduced from 53% to 16%; the renal clearance of both nalidixic acid and 7-hydroxymethylnalidixic acid are reduced (p < 0.001); the intrinsic t1/2 of the metabolite 7-hydroxymethylnalidixic acid increased from 0.48 h to 4.24 h. The amount of acyl glucuronidation of 7-hydroxymethylnalidixic acid was not altered. The in vitro protein binding of both acyl glucuronides was increased, while no effect on the unconjugated compounds was seen. Nalidixic acid had no effect on the maximal renal excretion rate of probenecid acyl glucuronide. PMID- 8220302 TI - G proteins and the heart. PMID- 8220304 TI - Catecholamines in Drosophila melanogaster (wild type and ebony mutant) decuticalarized retinas and brains. AB - The concentrations of catecholamines were determined in the decuticalarized retinas and brains at different ages in wildtype and ebony Drosophila melanogaster using the HPLC-technique with an electrochemical detector. L-Dopa, dopamine (DA), alpha-methyldopa (alpha-MD) and unidentified compounds X1, X2 and X3 were found in decuticalarized retinas and brains of wildtype and ebony at different ages. Retinas and brains of the mutant ebony have higher concentrations of L-Dopa, DA and alpha-MD than the wildtype. In both wildtype and ebony, the concentrations of X1, X2 and X3 were found to be higher in decuticalarized retinas than in brains. The identity and importance of X1, X2 and X3 are still unknown. PMID- 8220303 TI - The involvement of the cytoskeleton in regulating IP3 receptor-mediated internal Ca2+ release in human blood platelets. AB - In this study we have used saponin to permeabilize platelet membranes in order to test directly the involvement of IP3 in regulating internal Ca2+ release, and to measure IP3 binding to its receptor. Our results indicate that platelet vesicles release Ca2+ as early as 3 seconds after IP3 addition. Using [3H]IP3, we have found that platelets contain a single class of high affinity IP3 binding sites with a Kd of approximately 0.20 (+/- 0.01) nM. Immuno-blotting shows that platelets contain a 260 kDa polypeptide which shares immunological cross reactivity with brain IP3 receptor. Immunofluorescence staining data indicate that the IP3 receptor is preferentially located at the periphery of the platelet plasma membrane. Most importantly, both IP3 binding and IP3-induced Ca2+ release activities are significantly inhibited by cytochalasin D (a microfilament inhibitor) and colchicine (a microtubule inhibitor). These findings suggest that the cytoskeleton is involved in the regulation of IP3 binding and IP3 receptor mediated Ca2+ release during platelet activation. PMID- 8220305 TI - Carbohydrate metabolism of lung tissue of suckling and adult rats. AB - The carbohydrate metabolism of lung tissue of suckling (1-3 weeks) and adult (40 42 weeks) rats were investigated and compared. The results showed that the apparent km for in vitro glucose utilization was 3.13 nM for adult lung and the V max 136.99 mumol/g/h. This could not be determined for neonatal animals. The rate of glucose entry into the glycolytic pathway of adult lung was faster than in the lung of neonatal rats. However, glycogen utilization by neonatal lung was faster than by adult lung. The in vitro oxygen consumption of the lung tissue slices of both age groups were the same. It is proposed that the slower rate of glucose entry into glycolysis in lung tissue of suckling rats is due to a different hexokinase isoenzyme profile. It is also concluded that glycogen-glucose plays a major role in lung development. PMID- 8220306 TI - Effect of silica on the spontaneous cytotoxicity of axial organ cells from Asterias rubens. AB - Axial organ cells (A.O.) which are composed of phagocytes and lymphocytes from the sea star Asterias rubens exert a spontaneous cytotoxicity against mouse tumour cells. This toxicity was tested in the presence or absence of silica. It appears that phagocytes play the role of killer cells. PMID- 8220307 TI - Signalling in cell growth and death: adequate nutrition alone may not be sufficient for ciliates. A minireview. AB - The initial inoculum level of Tetrahymena in a chemically defined medium determines whether the cells are capable of exponential growth. Below 750 cells ml-1, the cells fail to go into exponential growth and will die within about 20 hours. By adding certain growth stimulants, death can be postponed and the cells begin to grow after a delay which depends on the intensity of the signal. The implication is that autocrine growth factor expression might be required for cells to grow, and that these stimulants either assist its production or lower the cell threshold to its action. The findings in Tetrahymena are reviewed, and the advantages of having a cell system in which all the components of the medium can be carefully controlled is recognised. PMID- 8220308 TI - EM evidence of myoblast origin in regenerating human skeletal muscle explants. AB - EM study of cultured human skeletal muscle explants on 10 consecutive days after incubation made possible a record for the first time, the early events occurring during regeneration. After incubation, normal myonuclei underwent activation and dense granulation. Some myonuclei showed early transformation to presumptive myoblasts. The conclusion was that myonuclei transformed into myoblasts which developed into satellite cells (SC). These SC of myonuclear origin, proliferated, and fused forming myotubes that matured into myofibres, replacing damaged muscle. The findings have new implications for the current myoblast/cell transplant and gene transfer therapy research which may provide possible answers for muscular dystrophy in the future. PMID- 8220309 TI - Insulin rescues the unicellular eukaryote Tetrahymena from dying in a complete, synthetic nutrient medium. AB - The presence of 10(-6) M bovine insulin in chemically defined nutrient medium prevented cell death and improved cell proliferation of the ciliate Tetrahymena pyriformis when inoculated at low initial cell density. The action of insulin was found to be restricted to the 22-30 fragment of the B-chain. These results suggest that small peptides are involved in regulation of cell survival and cell proliferation in Tetrahymena pyriformis. PMID- 8220310 TI - Changes on protein expression associated with salinity tolerance in Brassica cell cultures. AB - The synthesis of proteins from salt-tolerant Brassica oleracea L. var. botrytis L. subvar. cauliflora (Gars.) DC. (cauliflower) cell cultures is modified in relation to controls in several features. There are nine newly induced polypeptides in tolerant cultures (absent in control conditions). Some of them are only present under low salt levels (85 mM NaCl). Another group seems to be representative of moderate and high salt levels (170 and 255 mM NaCl), and a third group is present in all the salt conditions tested. On the other hand, the synthesis of most of the polypeptides present in control conditions is modified in salt-tolerant cultures by increasing, decreasing or stopping their synthesis in any of the tested conditions. The relationship between these changes in Brassica and other plant systems is discussed. PMID- 8220311 TI - Localization of MPM-2 recognized phosphoproteins and tubulin during cell cycle progression in synchronized Vicia faba root meristem cells. AB - MPM-2 antibody reacts with a subset of mitotic phosphoproteins. We followed localization of MPM-2 immunoreactive material and localization of microtubules during cell cycle progression in a highly synchronous population of Vicia faba root meristem cells and isolated nuclei. The MPM-2 antibody labelling showed significant cell cycle dependence. MPM-2 nuclear reactivity was weak and homogeneous in G1 and S phase of the cell cycle and became stronger and heterogeneous during G2, resembling staining of the nuclear matrix, with maximum staining at the G2/M interface. Similarly the staining intensity of nucleoli increased from late G1 phase to nucleoli dispersion in early prophase. During mitosis MPM-2 immunoreactivity was associated with spindle configurations and the brightest signal was localized in kinetochores from prophase to metaphase. PMID- 8220312 TI - Estrogen-regulated expression of a growth arrest specific gene (gas-1) in rat uterus. AB - gas-1 belongs to a family of growth arrest specific genes negatively regulated after growth induction of arrested cells. We report the expression of gas-1 in an in vivo system of cell proliferation. gas-1 mRNA accumulates progressively in the uterus of ovariectomized rats with a peak at three weeks after surgery. After estrogen treatment gas-1 mRNA levels decrease within two hours, at a time when c myc expression is greatly increased, and return to pretreatment levels at 48 hours. Treatment with cycloheximide does not prevent estrogen-induced down regulation of gas-1 mRNA levels. The present results show that: i) estrogen affects the uterine growth state by regulating the expression of both positively and negatively acting genes, ii) gas-1 expression is controlled by cellular growth state also in vivo. PMID- 8220313 TI - An elastinolytic enzyme detected in the culture medium of human arterial smooth muscle cells. AB - The culture medium of human arterial smooth muscle cells exhibits an elastinolytic activity with 68 and 64 kDa on elastin substrate gels. The enzymatic activities are inhibited by ethylenediamine tetraacetic acid, a metalloproteinase inhibitor, but not by other inhibitors of serine, cysteine and aspartic proteinases. The proteinase in the culture medium is activatable by 4 aminophenylmercuric acetate and degrades insoluble elastin. Compared to other matrix metalloproteinases (MMP), the activity shows the similar elastinolytic pattern to that by MMP-2 purified from human rheumatoid synovium, while MMP-3 and MMP-9 have different lytic patterns and MMP-1 possesses no elastinolytic activity. An immunoblot analysis demonstrated that the 68-kDa enzyme is MMP-2. An immunofluorescence study illustrates that MMP-2 is localized within the cytoplasm of the smooth muscle cells. These findings suggest that the elastinolytic enzyme secreted by human arterial smooth muscle cells is MMP-2. PMID- 8220314 TI - Production of the metastatic phenotype by DNA transfection in a rat mammary model. AB - A syngeneic, immunocompetent rat mammary model has been employed to investigate the molecular basis of the metastatic phenotype. Transfection of the benign rat mammary epithelial cell line Rama 37 with the gene for p9Ka; a small, rat, calcium-binding protein or DNA from metastatic human cell lines derived from a primary breast carcinoma or a pleural effusion yields transfectants with metastatic capabilities. Transfection of DNA from a benign human mammary cell line, a plasmid containing a cDNA for the human basic fibroblast growth factor (bFGF) gene, or the oncogene EJ-ras-1, fails to yield any transfectants expressing the metastatic phenotype. PMID- 8220315 TI - Induction of macrophage proliferation by heparin and heparan sulfate. PMID- 8220317 TI - Plant mucilages. XLIII. A representative mucilage with biological activity from the leaves of Hibiscus rosa-sinensis. AB - A representative mucilage, called Hibiscus-mucilage RL, was isolated from the leaves of Hibiscus rosa-sinensis L. It was homogeneous on electrophoresis, and its molecular mass was estimated to be roughly 1.0 x 10(7). Its intrinsic viscosity value in aqueous solution was 23.2. The major constituent is an acidic polysaccharide composed of L-rhamnose: D-galactose: D-galacturonic acid: D glucuronic acid in the molar ratio of 5:8:3:2. Methylation analysis, partial hydrolysis and nuclear magnetic resonance studies indicated its main structural features including a unique backbone chain composed of alpha-1,4-linked D galactosyl alpha-1,2-linked L-rhamnosyl alpha-1,4-linked D-galacturonic acid units. The mucilage showed considerable anti-complementary activity. PMID- 8220316 TI - Protein-free culture of Vero cells: a substrate for replication of human pathogenic viruses. AB - A protein-free chemically defined medium designated PFEK-1 was developed for culture of VERO cells on polyvinyl formal (PVF) culture surface without serum or other macromolecular supplements. VERO cells proliferated in PFEK-1 medium on PVF surface to a similar extent as cells in serum-supplemented medium without previous adaptation from serum-containing conditions. The protein-free culture infected with coxsackievirus B4, herpes simplex virus types 1 and 2, measles virus and poliovirus types 1, 2 and 3 developed viral titers comparable to those found in conventionally grown cells. The results demonstrated that VERO cells in protein-free culture provide a sensitive substrate for the production of human pathogenic viruses which are not contaminated by serum or other protein factors usually added to a culture medium. PMID- 8220318 TI - Influence of liposomes on tryptic digestion of insulin. II. AB - The mechanism of enhancement of tryptic digestion of insulin by empty liposomes was studied using HPLC analysis, gel filtration (insulin binding to the liposome and lipid transfer to the insulin) and an electrokinetic study using the zeta meter (trypsin binding to the liposome). Soybean phosphatidylcholine (PC), phosphatidic acid (PA) [PA/PC = 1/9] and stearyl amine (StA) [StA/PC = 1/9] were used as neutral, negatively charged and positively charged liposomes, respectively. Tryptic digestion of insulin was enhanced by reducing the liposome size from 150 to 40 nm when neutral empty liposomes were used. The amount of insulin bound to neutral empty liposomes increased on reducing liposome size. Nevertheless, no strong evidence of trypsin binding to neutral empty liposomes was obtained. The amount of liposome-bound insulin was greater for PC than StA/PC and PA/PC, and the amount of lipids transferred to insulin decreased in the following order; StA/PC > PA/PC > PC. These findings suggest that the positively charged liposome did not enhance tryptic digestion, because insulin was protected from tryptic digestion by surrounding lipids from positively charged liposomes (StA/PC). Trypsin bound to the PA/PC liposomes, but not to the PC or StA/PC liposomes. PMID- 8220319 TI - Purification and characterization of zinc-dependent acid phosphatase from bovine brain. AB - Zn(2+)-Dependent acid phosphatase (Zn(2+)-APase) was purified to homogeneity from bovine brain. The apparent molecular weight of the enzyme was estimated to be about 62000 by gel filtration and 31000 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The enzyme exhibited an isoelectric point of approximately 4.8. The enzyme required Zn2+ ions for catalytic activity, but other cations had little or no effect. The maximum enzyme activity was obtained in the presence of about 5 mM of Zn2+ at pH 5.5 in 50 mM 2-(N morpholino)ethanesulfonic acid-NaOH buffer. The enzyme significantly catalyzed the hydrolysis of p-nitrophenyl phosphate, phenyl phosphate, and phosphotyrosine. The enzyme was also active for myo-inositol-2-monophosphate and adenosine 2' monophosphate of the other common phosphate esters tested, though significantly less active than for p-nitrophenyl phosphate. The optimum activity pH of the enzyme was around 5.5 with p-nitrophenyl phosphate and myo-inositol-2 monophosphate. The enzyme was resistant to fluoride ions. Two types of Zn(2+) APases, a high molecular weight (molecular weight, M(r)., about 110,000) and a low molecular weight (M(r), about 62,000) type, were found to exist in various tissues of rat. Brain, lung, spleen, stomach, heart, skeletal muscle, and erythrocytes contained only the lower molecular weight type. On the other hand, liver and kidney contained mainly the higher molecular weight type, and the small intestine contained significant quantities of the both types. PMID- 8220320 TI - Respiration-driven Na+ pump of the marine Vibrio is encoded by chromosomal DNA. AB - A plasmid-cured strain of the marine Vibrio alginolyticus 138-2 retains a respiration-driven Na+ pump. Examinations of several strains of V. alginolyticus and V. parahaemolyticus revealed that these murine Vibrio always possessed the respiration-driven Na+ pump irrespective of the presence or absence of plasmids. These results strongly suggested that the genes for the Na+ pump were encoded by chromosomal DNA. PMID- 8220321 TI - Purification and characterization of a morphine UDP-glucuronyltransferase isoform from untreated rat liver. AB - A morphine UDP-glucuronyltransferase was purified from liver microsomes of untreated Sprague-Dawley rats. A new gel, omega(beta-carboxypropionylamino)octyl Sepharose 4B, was prepared by coupling monomethylsuccinate with omega-aminooctyl Sepharose 4B and this was used as an efficient tool for the separation of microsomal enzymes. Emulgen 911 solubilized microsomes were applied to a column packed with the gel and eluted at pH 7.4 while increasing KCl concentration in a stepwise manner. An isoform was further purified with UDP-hexanolamine Sepharose 4B gel. The purified UDP-glucuronyltransferase (morphine UGT of untreated rat, morphine UGTUT) exhibited a molecular weight of 52000 on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and was capable of glucuronidating the 3 hydroxyl group of morphine. The isoform catalyzed to a small extent the glucuronidation of 4-hydroxybiphenyl; however, no glucuronidation activity towards androsterone, testosterone, bilirubin, 4-nitrophenol and the 6-hydroxyl group of morphine was observed. The difference in properties, compared with morphine UGT (molecular weight 56000) which was purified previously from phenobarbital-treated rats, is discussed. PMID- 8220322 TI - Enhancement of tumor growth by morphine and its possible mechanism in mice. AB - The effect of morphine on tumor growth of EL-4 leukemia in C57BL/6 mice and of Sarcoma 180 carcinoma in ddY mice was studied. Local subcutaneous tumor growth was enhanced by morphine (10 mg/kg, s.c.) given daily for 10d. This effect was inhibited by preadministration of the opioid antagonist naloxone. However, naloxone alone had no significant effect on tumor growth. Morphine also enhanced tumor growth in C57BL/6 mice inoculated i.p. with P388 as well as Meth-A cell in Balb/c mice. However, incubation of morphine with cultures of EL-4, P388, MM-46 and Meth-A cells failed to enhance tumor growth. Mice given morphine displayed marked atrophy and reduced cellularity of the spleen and thymus. The humoral response to sheep erythrocytes and T- and B-cell responses to foreign antigens were suppressed, and the lymphocyte proliferative response to T- and B-cell mitogens (concanavalin A and bacterial lipopolysaccharide, respectively) was attenuated. Morphine exerted an inhibitory effect on the immune response which was antagonized by the concomitant administration of naloxone. These data suggest that the enhancement of tumor growth by the administration of morphine is the result of a overall immunosuppressive effect. The significance of the immunomodulatory effect of morphine is discussed in this report. PMID- 8220323 TI - Antinociceptive effect of dihydroetorphine and its tolerance/dependence liability in mice. AB - The profile of actions of dihydroetorphine (DHE) concerning antinociception, tolerance and dependence was compared with those of morphine in mice. DHE at 1, 5, 10 or 20 micrograms/kg produced an antinociceptive effect in a dose dependent manner and 10 micrograms/kg was nearly equipotent to that of 10 mg/kg of morphine. The antinociceptive effect of both drugs was completely suppressed by 1 mg/kg of naloxone, while neither 10 mg/kg of naltrindole nor 1 mg/kg of nor binaltorphimine had any suppressive effect. Mice tolerant to morphine antinociception were tolerant to DHE and vice versa. The naloxone-sensitive, locomotor accelerating activity was progressively enhanced by daily administration of DHE and morphine and a cross reverse tolerance developed between these compounds, suggesting that common mechanisms, especially mediating opioid receptors, underlay the activity enhancement. The development of physical dependence as evidenced by naloxone precipitated withdrawal signs, however, was not observed with daily treatment with DHE, 10, 20 and 100 micrograms/kg for 6 d. Thus, we demonstrated that DHE produces the antinociceptive effect mediated through mu opioid receptors without causing development of a physical dependence, suggesting that it is safe to use in the clinical therapy of patients suffering severe pain such as that accompanying cancer. PMID- 8220324 TI - Antitumor activity of a novel nucleotide derivative, 5'-(1,2-dipalmitoyl-sn glycero-3-phospho)-5-fluorouridine (TJ14026) on murine tumors. AB - The antitumor activity of a nucleotide derivative, 5'-(1,2-dipalmitoyl-sn-glycero 3-phospho)-5-fluorouridine (TJ14026), was confirmed following both intraperitoneal and oral administration against a number of murine experimental tumor systems in vivo, which included Meth A fibrosarcoma, B16 melanoma, 5 fluorouracil (5-FU) resistant P388 leukemia, P815 mastocytoma and L5178Y-ML lymphoma. Successive i.p. injections of a small dose (10 mg/kg/d x 10) or intermittent i.p. injections of a larger dose (50 mg/kg/d x 3) were equally effective against the solid form of Meth A fibrosarcoma. Intraperitoneal injection of TJ14026 prolonged the life of mice with 5-FU resistant P388 leukemia. Oral administration of TJ14026 was also effective against P815 mastocytoma and L-5178Y-ML lymphoma in the liver, an P388 leukemia metastasized to the lymph nodes. Glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels were elevated in the serum of un-treated mice bearing P815 mastocytoma but not in mice treated with TJ14026. PMID- 8220325 TI - Preventive effects of a traditional Chinese medicine (sho-saiko-to) against oxygen toxicity and membrane damage during endotoxemia. AB - The preventive effects of a traditional Chinese medicine Sho-saiko-to (Kampo prescription, TJ-9) were determined from oxygen toxicity and membrane damage in liver during endotoxemia. The liver lipid peroxide level and xanthine oxidase activity 18 h after administration of endotoxin (6 mg/kg, i.p.) to TJ-9 (500 mg/kg/d, p.o.)-pretreated mice were markedly lower than that in endotoxin-treated mice, whereas the administration of TJ-9 significantly increased superoxide dismutase and glutathione peroxide activities in liver of endotoxin-injected mice. In the mice pretreated with a TJ-9, the levels of alpha-tocopherol and nonprotein SH in liver tissue 18 h after endotoxin injection were markedly increased as compared to those in endotoxin-treated mice. Leakages of acid phosphatase and lactate dehydrogenase isozyme in serum were markedly lower in endotoxin-TJ-9-treated mice than those in mice given endotoxin. The administration of TJ-9 clearly prevented the membrane protein damage arising from endotoxin challenge. Kampo prescription Sho-saiko-to thus appears to protect the liver plasma membrane from injury by free radicals which occur in a tissue ischemic state during endotoxemia. PMID- 8220326 TI - Carbonic anhydrase inhibitors from the pericarps of Punica granatum L. AB - Seven highly active inhibitors against carbonic anhydrase (CA, EC 4.2.1.1), punicalin (2), punicalagin (3), granatin B (5), gallagyldilactone (7), casuarinin (8), pedunculagin (9) and tellimagrandin I (10), and four weakly active inhibitors, gallic acid (1), granatin A (4), corilagin (6) and ellagic acid (11), were isolated from the pericarps of Punica granatum L. (Punicaceae). They are ellagitannins. The type of inhibition by 3 and 7 using p-nitrophenyl acetate as a substrate, is noncompetitive. The structure-activity relationship of inhibitory effects on CA is discussed. PMID- 8220327 TI - The influence of glucagon on the hepatic transport of taurocholate in isolated perfused rat liver: kinetic analysis by the multiple indicator dilution technique. AB - Glucagon has been demonstrated to stimulate the uptake of bile acid in isolated rat hepatocytes (Am. J. Physiol., 249, G427 (1985)). In the present study, we determined the influence of glucagon on the hepatic transport of a bile acid, taurocholate (TCA), in isolated rat livers. A single-pass perfusion and a rapid injection, multiple indicator dilution method were employed. The hepatic availability at steady-state was 0.04. With the presence of glucagon in the perfusate (from 10(-9) to 10(-7) M), the bile flow rate was stimulated by 30%, while hepatic availability was decreased from 0.04 to 0.02 with a stepwise increase in glucagon concentration. Thirty min after the infusion of glucagon (300 nM), [3H]TCA and [14C]inulin were injected in a bolus state into the portal vein, and the outflow was collected at 1.0 s intervals over 30 s. Glucagon decreased the instantaneous hepatic availability by 50% compared to the control level, and was thus compatible with the steady-state experiments. In the control experiment, the influx clearance (PSinf) was 20 times higher than the efflux clearance (PSeff). Glucagon (300 nM) in the perfusate enhanced PSinf by 50% of the control, whereas sequestration clearance (CLseq) and the biliary excretion rate constant remained unchanged. PSeff was stimulated to 2 times the control, but still remained much smaller than CLseq. Based on the comparison of PSinf, PSeff and CLseq, the rate-determining process of TCA hepatic elimination was the influx process in both the presence and absence of glucagon. Taken together, the enhancement of the influx process was responsible for the decrease in TCA hepatic availability caused by glucagon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8220328 TI - Pharmacokinetics of a micronized, poorly water-soluble drug, HO-221, in experimental animals. AB - N-[[[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]amino]carbonyl] - 2 nitrobenzamide (HO-221) is presently under development as an oral anticancer agent with a novel mode of action. However, HO-221 exhibits extremely poor bioavailability after oral administration because it is only slightly soluble in water (0.055 micrograms/ml at 37 degrees C). Our previous study revealed that the micronization of HO-221 to the submicron region improved this oral bioavailability. In this study, the oral pharmacokinetics of this micronized HO 221 was investigated in rats, dogs and monkeys. After oral administration, the agent was moderately absorbed with the Tmax of 6.5-8.0, 17.3-20.0 and 12.0 h, and eliminated with the terminal half-lives of 11.9-15.0, 66.8-78.3 and 42.3 h in rats, dogs and monkeys, respectively. The bioavailability was incomplete (3.7 21.4%). In rats, the plasma concentration did not increase proportionally with increasing oral doses. In dogs, food enhanced the bioavailability 2.2-fold with a standard meal and 3.6-fold with a high fatty meal as compared with fasting conditions. PMID- 8220329 TI - Modulation of morphine action by lauric acid. AB - Intraperitoneal administration of lauric acid (C12) at the high doses, 100-1000 mumol/kg, showed weak but dose-dependent antinociceptive effect in mice. Pretreatment of the animals with 0.1 mumol/kg of i.p. C12 tended to suppress the antinociceptive effect of 7 mg/kg of s.c. morphine and daily combination of this dose of C12 with 10 mg/kg of s.c. morphine blocked the development of antinociceptive tolerance to morphine. However, increasing or decreasing of the dose of C12 resulted in the loss of its modulatory effect on morphine. The strict dose-dependency of C12 in its action on morphine suggests that there is a regulatory role for C12, a medium length straight chain fatty acid, in the endogenous pain inhibitory system. PMID- 8220330 TI - Decline in plasma membrane Ca(2+)-ATPase activity and increase in cytosolic-free Ca2+ concentration of endotoxin-injected mice livers. AB - The present study describes the activity of Ca(2+)-ATPase in liver plasma membrane and cytosolic-free Ca2+ concentration ([Ca2+]i) in an individual vital cell in mouse liver 18 h after endotoxin administration. Ca(2+)-ATPase activity in liver plasma membrane in the poisoned mice was markedly decreased to 28% of that in the control. The membrane protein damage in liver was found mostly in the molecular weight (M.W.) regions near 60,000-150,000 in endotoxemic mice, and was markedly injured near 140,000 (M. W. of Ca(2+)-ATPase in liver plasma membrane). The level of [Ca2+]i in liver cells in endotoxin-poisoned mice was greater at 18 h postintoxication than that of the control. These findings suggest the possibility that the depression of Ca(2+)-ATPase activity in liver plasma membrane in mice may contribute to membrane damage caused by the endotoxin, and that the increase of [Ca2+]i in liver cytoplasm may partially explain various endotoxin-induced metabolic disorders. PMID- 8220331 TI - Structures of mefenamic acid metabolites from human urine. AB - Three major metabolites of mefenamic acid were isolated from the urine of a normal adult man receiving mefenamic acid orally. The structures of those metabolites were determined as glucuronides of mefenamic acid, its hydroxymethyl derivative, and its carboxylic acid derivative on the basis of spectral data. PMID- 8220332 TI - Phytogrowth-inhibitory activities of sulfur-containing compounds. II. The inhibitory activities of thiosalicylic acid and dihydro-2(3H)-thiophenone-related compounds on plant growth. AB - Thiosalicylic acid (I) showed rather strong inhibitory activity on the growth of roots of all plants treated except Abelmoschus esculentus Moench at the concentration of 5.0 x 10(-4) M. This compound strongly inhibited the growth of the root of Echinochloa utilis Ohwi et Yabuno even at the low concentration of 5.0 x 10(-5) M. Dihydro-2(3H)-thiophenone (VII) also exhibited inhibitory activity on the growth of roots of all plants treated except Glycine max Merrill. Both compounds inhibited the germination of seeds of some plants at the concentration of 1.0 x 10(-3) M. In I-related compounds (I-V), methyl acetylthiosalicylate (IV) had the strongest inhibitory activity, while in VII related compounds (VII-XI), 4-hydroxy-2(5H)-thiophenone (VIII) showed the most potent inhibitory activity. The amount of chlorophyll in the cotyledon of Brassica campestris L. subsp. rapa Hook. f. et Anders treated with all compounds except tetrahydrothiophene (XI) was lower than that of the control group. PMID- 8220333 TI - [Psychophysiologic aspects of occupational flying]. AB - The paper deals with advanced research on psychophysiology of flying activity to solve a triune task: to humanize the character and means of labour, to maintain a high level of working capacity and to develop professionally important psychophysiological features of flying personnel. The solution of the first task is associated with consecutive realization of the principle of actualization, an increase of psychophysiological capabilities of a man with the use of technical means in designing aeronautical engineering. Assurance of high functional reliability of flying personnel requires the development of the methods to evaluate and predict the state of psychophysiologic reserves during flying activities; the refinement of the norms of flight load on the basis of determining the quantitative interactions between a complexity level of flight assignments and a degree of decrease in reserve capabilities; the search for means and methods of correcting functional state directly in flight and accelerated recovery of performance postflight. The solution of psychophysiologic aspects of the professional reliability of pilot should be the development of a flight capabilities theory and theory-based improvement of estimation methods, development of methods and technical means for their improvements. PMID- 8220334 TI - [Psychosomatic status and quality of work of pilots in years of the quiet and the active sun years]. AB - The study indicated that with an increased solar activity the body systems of highly anxious (HA) flight-operators as compared to low anxious (LA) operators reach a new, more intensive level of functioning. Such a condition of the physiological status in HA operators goes together with a sharp rise of pilot mishandling in flying technique, a decrease in working capacity which along with other characteristics are indicative of a fall in the central nervous system functioning during active versus quiet sun year. The LA operators capacity to maintain the homeostasis during active sun year at a level of the quiet one affects positively flying longevity and less pronounced, as compared to HA operators, increase of pilot mishandling in flying technique during the active sun year. PMID- 8220335 TI - [The effect of motivational and emotional aspects of work on the structure of operator's errors]. AB - The paper studies a motivation effect on an effectiveness of occupational activities of the operators with a different level of anxiety. To do this, the role of professional motivation under co-existence of competing motives as well as the dynamics of interactions of the operators with different level of anxiety under complicated working conditions have been studied. It is indicated that the results of operator activity depends on hierarchical structure of motivation sphere. Emotional tension induced by the main motive may lead to an increment of by-work failures. In a motives conflict situation highly anxious operators are more immune to disturbances than the low anxious persons. A reliability of joint activity of the operators exhibiting a close level of anxiety is higher than in operators with different values of an anxiety level. PMID- 8220336 TI - [Effects of weightlessness on sensorimotor interaction in the operator'work: proprioceptive feedbacks]. AB - During the 2nd Soviet-French Space Flight an operator ability to reproduce from memory the different positions of handles was studied. It is indicated that the temporal parameters of movement and the number of distinguishable positions of handle were not significantly influenced by microgravity effect. However, the accuracy of setting the handle to a given position at the beginning of the flight was significantly lower with an error towards a decrease of handle deflection angle. It is assumed that the cause of this is the proprioceptive feedbacks changes. PMID- 8220337 TI - [Basic biochemical blood parameters in astronauts in preflight training]. AB - From the findings of biochemical blood analyses obtained during original examinations of 24 cosmonauts with a repeat blood sampling (2-5 times) of each test subject there calculated the mean values of norm and the interval limits of norm using 33 biochemical blood indices for a given group of test subjects. It is shown that in the absence of significant discrepancies from the generally used mean population standards for the cosmonauts it is typical of some specific differences from universally adopted standards of the parameters mainly related to energy metabolism. PMID- 8220338 TI - [Structural and functional disorders of erythrocyte membranes in simulated extravehicle space work]. AB - The experimental data on a structural-and-functional status of erythrocyte membranes in ground-based simulation of human extravehicular activity (EVA) are discussed. The changes in the structure and function of erythrocyte membrane were determined from the fixation of lipophilic ions, specific activity of ion transporting adenosine triphosphatases and content of the products of peroxide oxidation of lipids (POL) in plasma. On exposure to hypobaric hyperoxia during real EVA the membrane status changes are associated with the activation of a cascade of POL processes. PMID- 8220339 TI - [Effect of space flight and head-down position on motoneuron- glia-capillary system of the rat bone marrow]. AB - In the anterior horns of the rats exposed to a 14 day space mission and 8-11 hrs of earth gravity environments postflight there occurred morphologic changes pointing to the motoneuron hypofunction which was expressed to a greater extent in motoneurons at C3-C4 level than at L4-L5 level. As the time of the rat stay under Earth gravity conditions following 14-day space mission is increased up to 48-51 hrs the structural changes in the motoneuron-glia capillary system at the L4-L5 level is indicative of an activation of spinal cord motoneurons. The 14 day head-down suspension (HDS) of the rats results in the morphologic changes in anterior horns which are an indication of hyperfunction of motoneurons in cervical enlargement and hypofunction of motoneurons in lumbar enlargement of the spinal cord. An increase of HDS time up to 32 days intensifies the morphologic changes in lumbar enlargement motoneurons. A lesser extent of morphologic changes manifestation in the motoneuron-glia-capillary system at L4-L5 level in the rats following a 14-day HDS as compared to the rats exposed to 14-day space mission is indicative of more slower development of motoneuron hypofunction under Earth gravity conditions as opposed to space environments. PMID- 8220340 TI - [Body fluid and electrolyte content in rat tissues after space flight in the "Space-2044" spacecraft]. AB - Contents of water, sodium, calcium and magnesium in different tissues of the rats stayed in space for 2 weeks in healing period of bone fracture following graded trauma of calf-bones as well as in the rats exposed to a head-down suspension (HDS) have been studied. In microgravity-exposed animals there were no significant changes in fluid-electrolyte composition of the liver, kidney, myocardium, skin, bone (calf bone). Specific "functional load" on the system of fluid-electrolyte homeostasis in the form of operation and subsequent healing of bone fracture did not result in additional changes in fluid and electrolyte contents of body tissues. In the HDS animals there was a significant change in fluid-electrolyte composition of skin, kidney and bone tissue. PMID- 8220341 TI - [Lipid peroxidation and antioxidant defense system in rats after a 14-day space flight in the "Space-2044" spacecraft]. AB - After 14-day space flight of rats onboard Cosmos 2044 in their blood plasma, homogenates of liver, skeletal muscles and myocardium there were determined the parameters of peroxide oxidation of lipids (POL) and system of antioxidant defense: content of dienic conjugates (DC), malonic dialdehyde (MDA), schiff bases (SB), tocopherol (TF), total antioxidative activity (AOA, only in plasma), activity of antioxidative enzymes (only in tissues) superoxide (SOD), catalase, glutathione-peroxidase (GP), glutathione-reductase (GR). In the animal liver there was a decrease in SB content and an increase of SOD, catalase and GP activities. Skeletal muscles exhibited a reduced SB concentration. In myocardium there was a reduction of DC and SB levels, activity of GR with an increase of TF concentration, activity of SOD and catalase. In the blood plasma there occurred a decline of SB and TF contents and an elevation of MDA and total AOA concentrations. The authors drew a conclusion about a compensated process of POL in the tested animals and about the relation of the observed changes with body response to the final phase of the space mission and acute gravitational stress during a readaptation to the Earth environments. On the basis of the analysis of similar data from shorter-duration space experiments, the noted changes in the parameters of the system of POL and antioxidant defense are considered a universal response which does not directly depend on duration of the orbital phase of a space mission. PMID- 8220342 TI - [Comparative analysis of weightlessness and hypergravity effects on erythropoiesis in male and female mammals]. AB - The paper summarizes the data obtained in the investigations of bone marrow and blood of Wistar rats exposed to microgravity (Cosmos biosatellites) or 2 G hypergravity (centrifuge). Males, females and pregnant females at various stages of pregnancy have been examined. Under the gravity in the range of +/- 1 G with respect to the earth gravity, in all experiments there were similar changes in erythroid hemopoiesis: a decrease in the total count of blood red cells of bone marrow; a decline in the blood reticulocyte concentrations. There changes in the erythroid part of the rats bone marrow were practically the some in space flights of 7, 14 and 22 days of duration in the centrifuge experiments with animals there alterations were maximal following a 5-day exposure and were absent after one month. Possible reasons of the above changes are discussed stay in 2 G environment. PMID- 8220343 TI - [Changes in some parameters of carbohydrate and lipid metabolism in rats with adrenaline administration in the rehabilitation period after hypokinesia]. AB - Changes in the blood levels of glucose, lactate and free fatty acids, and glycogen in the livers and skeletal muscles of rats (n = 47) on epinephrine administration (150 mcg/kg body weight) were studied on Day 7 of a recovery period following hypokinesia of 15 and 30-day durations. In the animals exposed to restrained motor activity, as compared to normal rats, epinephrine has a less effect on glycogen content in the muscle, is not accompanied by increased serum levels of free fatty acids and results in more marked elevation of blood lactic acid levels. Adrenal control of lipolytic processes in the adipose tissue and of glycogenolytic processes in the muscles in the post-hypokinetic recovery period is reduced. PMID- 8220344 TI - [A device to stimulate sea sickness in horizontal and head-down positions]. AB - A device enabling to expose small laboratory animals (rabbits, cats, etc.) to sea sickness using the swing with one suspended bar in an automatic mode both in horizontal and head-down position with different tilt angles has been developed. The device can be used for affecting during unlimited periods of time the otolith apparatus and semicircular canals in combination, if need be, with antiorthostatic hypokinesia. The design provides quick and easy installation of the container with an animal in horizontal or head-down position. PMID- 8220345 TI - [Evaluation of calcium content in the human spine by in vivo neutron activation]. AB - A technique of in vivo neutron activation analysis (NAA) of calcium levels in lumbar, thoracic and cervical segments of the spinal column separately and as a whole has been developed. Special device provides selective irradiation by neutrons of a vertebral segment under study while a highly-sensitive spectrometric unit registers radionuclides induced in bone tissue during radiation exposure. For radiation exposure 5 or 10 238Pu-Be neutron sources with 5.10(7) neutrons s-1 output of each source are used. The spectrometric unit consists of 4 scintillation detectors with NaI (Tl) crystals of 150 mm in diameter and 100 mm- thickness arranged in a line tightly one after another. The time of exposure depends on the number and mutual arrangement of the neutron sources and is selected given the dose equivalent at depth of positioning of the spinal cord does not exceed 1 cZv (REM), the quality factor for fast neutrons equals 10. The recording duration is 20 min, the intervals between radiation exposure and recording do not exceed 3 min. The magnitude of the total error of an individual measurement estimated by reproducibility of the data obtained in 2 series of in vivo NAA of the spinal calcium levels in 6 volunteers with the use of 5 neutron sources amounts to an average of 4.8%. When used 10 sources, this error can be reduced to 2.0-3.2%. PMID- 8220346 TI - [Professional psychophysiologic expertise of astronauts]. AB - Occupational psychophysiological expertise of the cosmonauts is a very important problem of the space psychophysiology. The paper deals with the scientific-and practical, methodologic and theoretical aspects of psychophysiologic expertise of the cosmonauts of which the major problems are: principles and directions of psychologic expertise of cosmonauts, psychophysiologic qualities required for successful mastering and performing the work as a cosmonaut; predicting occupational fitness of cosmonauts; the main requirements for the procedures of psychophysiologic examination; methodical recommendations with respect to performing psychological expertise. The procedures used during psychophysiologic expertise of the cosmonauts and the method of making a conclusion on the basis of the results of psychologic examinations using these procedures. PMID- 8220347 TI - [Vestibular reactions in man after breathing helium oxide under 26 atm pressure]. PMID- 8220348 TI - [A compound, isolated from the algae Laminaria Saccharina to increase animal survival in acute cooling,radiation injury and water deprivation]. PMID- 8220349 TI - Caring without politics: lessons from the first nurses of the North and South. PMID- 8220350 TI - The educational and philosophical influences on Florence Nightingale, an enlightened conductor. PMID- 8220351 TI - Nursing uniforms: romantic idea, functional attire, or instrument of social change? PMID- 8220352 TI - Nursing and medical care in Finland from the eighteenth to the late nineteenth century: the background for the introduction of nurses' training in Finland in 1889, with some comparisons with developments in Sweden. PMID- 8220353 TI - Unity amidst difference: the ICN project and writing international nursing history. PMID- 8220354 TI - White nurses, black midwives, and public health in Mississippi, 1920-1950. PMID- 8220355 TI - Constructing the mind of nursing. PMID- 8220356 TI - Midwives as wives and mothers: urban midwives in the early twentieth century. PMID- 8220357 TI - Jane A. Delano: saint or sellout? PMID- 8220358 TI - "Of logical necessity ... they hang together": nursing and the woman's movement, 1901-1912. PMID- 8220359 TI - A new patient focused index for measuring quality of life in persons with severe and persistent mental illness. AB - The quality of life in persons with severe and persistent mental illness is often poor. Most treatment programmes have the goal of increasing quality of life. Unfortunately, existing methods to assess quality of life are cumbersome and oriented towards research rather than clinical settings. This study describes preliminary steps in the development, testing and application of a new patient focused index for measuring quality of life in persons with severe mental illness. The Quality of Life Index for Mental Health (QLI-MH) differs from existing instruments in that it is based on an easy to use, self-administered questionnaire that assesses nine separate domains that together encompass quality of life. Each domain can be individually weighted depending on its relative importance to the patient. Different parts of the instrument solicit information from the patient, the primary clinician, and, when available, the family. The instrument and its scoring system address limitations of previous approaches to quality of life measurement. PMID- 8220360 TI - Using multidimensional health measures in older persons to identify risk of hospitalization and skilled nursing placement. AB - We examine the relationship between multidimensional measures of function and outcomes in a cohort of older persons admitted to the residential care level of a multi-level long-term care facility. We collected self-reported measures of various aspects of health using the Medical Outcome Study Short-form Health Survey (SF-20) and the Dartmouth COOP charts, as well as performance-based measures of physical and cognitive function. Subjects (mean age 84.3 years) were followed for a median of 557 days. In multivariate analyses, emotional function (measured by either the SF-20 or COOP method) was a predictor of placement in skilled care. Self-reported overall health (measured by either the SF-20 or COOP method) and timed manual performance were predictive of hospitalization. Change on the functional status measures between 2 points in time was not associated with later placement in skilled care except in the case of timed manual performance. In an older population at risk for frequent and numerous health events, this study shows that two popularized self-report methods for assessing function yield results that predict future outcomes of great importance to older persons. However, measures that predict use of long-term care may not predict use of the hospital and vice versa. PMID- 8220361 TI - Quality of life: status and change (QLsc) reliability, validity and sensitivity of a generic assessment approach tailored for diabetes. AB - The aim was to review the psychometric properties of a generic strategy for assessing status and change in quality of life (QLsc) partly tailored for patients with insulin-dependent diabetes mellitus. Quality of life was defined as perceived well-being and life satisfaction, globally as well as within key domains and functions. The strategy has been developed iteratively and, thereby, proven psychometrically satisfactory across groups and settings. Seventy-three consecutive outpatients were examined in 1988, after a period on multiple injection treatment by insulin pen; 66 were re-examined in 1990. In 1988 and 1990, perceived well-being and life domain status were self-rated. Life domain changes attributed to pen treatment were rated retrospectively in 1988 and subsequent general changes over 2 years rated similarly in 1990. Shortened parallel ratings were performed by significant others. Series of cross-sectional and longitudinal analyses yielded convincing reliability, validity and sensitivity evidence of various kinds for all ratings, irrespective of rater-self or significant other. As expected, a consistent correlational pattern emerged between status self-ratings, suggesting 'the better/worse off' in one sense, the 'better/worse off' in other senses assessed. Moreover, congruent change linkages, suggesting 'the greater change for the better/worse' according to the one type, the 'greater change for the better/worse' according to the other one, were also salient. Fourteen persons with less congruence in the disparate, but parallel change rating parameters appeared to be in a critical disease phase, applying reaction formation or denial like defence mechanisms. In conclusion, the entire cohesive strategy also functioned well in the current setting. It may probably be applied in search for other vulnerable sub-groups and in analyses of coping strategies. It offers rich analytic options especially in evaluational contexts. The study outcome may stimulate development of methodology within this field. PMID- 8220362 TI - Background factors, long-term complications, quality of life and metabolic control in insulin dependent diabetes. AB - Sixty-six of 74 adults with Insulin Dependent Diabetes Mellitus (IDDM) examined earlier (1988), were followed up two years later (1990) with the aim of studying the influence of sociodemographic factors, long-term complications and quality of life on metabolic control. It was found that both non-cohabitance and a major discrepancy between quality of life change ratings made prospectively (difference in current QOL ratings made 1990 vs 1988) and retrospectively (assessed in 1990 and covering the same period) were associated with poorer metabolic control, and also that perceived somatic health was linked with better metabolic control. A majority of the persons with a major discrepancy in their quality of life ratings, seen as suggestive of difficulties in their realistically assessing their own life situation, was also found to be non-cohabitant and/or to have incipient nephropathy, indicating these persons to constitute a risk group. In addition, well-regulated subjects were found to rate their bodily health as higher than they did their quality of life, whereas for poorly regulated persons the opposite was the case. The results were seen as pointing to the need of paying special attention clinically to the group of persons characterized here by a major discrepancy in their quality of life change ratings and also as emphasizing the fact that living with IDDM is a balancing act for the individual between satisfying bodily demands to be well-regulated and living in such a way as to perceive quality of life. PMID- 8220363 TI - The European Organization for Research and Treatment of Cancer. Approach to quality of life assessment: guidelines for developing questionnaire modules. EORTC Study Group on Quality of Life. AB - The EORTC Study Group on Quality of Life (the Study Group) has adopted a modular approach to quality of life (QOL) assessment in cancer clinical trials. A 'core' instrument-the QLQ-C30-has been designed to cover a range of QOL issues relevant to a broad spectrum of cancer patients. It is intended that this QLQ-C30 be supplemented by more specific subscales ('modules') to assess aspects of QOL of particular importance to specific subgroups of patients. Since individual members of the Study Group were to be involved in module development, guidelines were required to standardize the module development process in order to ensure uniformly high quality across modules. These guidelines are presented in this paper. The term 'module' is defined, the composition of modules is outlined, and the criteria used to develop modules are specified. The module development process, consisting of four phases (generation of relevant QOL issues, operationalization of the QOL issues into a set of items, pretesting the module questionnaire, and large-scale field-testing) is described in detail. Further, issues related to cross-cultural instrument development, and the need for monitoring the module development process from within the Study Group are discussed. Finally, experiences with developing two site-specific modules (i.e., for head and neck, and breast cancer), are presented and the extent to which the guidelines meet practical requirements is discussed. The guidelines appear to provide a practical tool for module construction, that can facilitate the development of a comprehensive system for assessing the QOL of cancer patients internationally. PMID- 8220364 TI - Quality of life assessments and levels of decision making: differentiating objectives. AB - The purpose of this paper is to examine uses of quality of life (QOL) measurements at different levels of decision making within the health care system, ranging from the micro (clinical) level, through the meso (agency, institutional or regional) level to the macro and meta (governmental) levels. We use individualized, group and population-based QOL and preference assessments as illustrative examples of ways in which QOL information and decision making level interact. We conclude that the meso and macro levels pose particularly challenging problems, and suggest that, if the primary emphasis is placed on applications of QOL assessments at the micro (clinical) level of decision making, a research agenda that is much too limited may be adopted. PMID- 8220365 TI - Ethical principles and theories. AB - Ethical theory about what is right and good in human conduct lies behind the issues practitioners face and the codes they turn to for guidance; it also provides guidance for actions, practices, and policies. Principles of obligation, such as egoism, utilitarianism, and deontology, offer general answers to the question, "Which acts/practices are morally right?" A re-emerging alternative to using such principles to assess individual conduct is to center normative theory on personal virtues. For structuring society's institutions, principles of social justice offer alternative answers to the question, "How should social benefits and burdens be distributed?" But human concerns about right and good call for more than just theoretical responses. Some critics (eg, the postmodernists and the feminists) charge that normative ethical theorizing is a misguided enterprise. However, that charge should be taken as a caution and not as a refutation of normative ethical theorizing. PMID- 8220366 TI - Ethical models: facilitating clinical practice. AB - Modern health care presents significant dilemmas in nursing practice. Nurses are often entangled in the web of conflicts between the principles of autonomy, beneficence, and justice in managing the health care concerns of individuals, nurses, and the health care team. However, to achieve resolution the nurse needs an ethics model with which to determine appropriate care practices. According to the concept of autonomy, each individual has the fundamental right of self determination in health care decisions. At the same time, the nurse strives toward beneficent care for individuals through the delivery of health care. Tension between these two principles generally is minimal. It is only when conflicts exist between the autonomous patient and the beneficent nurse that ethical problems surface. At these times, respect for individual freedom and the interest in doing good are juxtaposed. Nurses may have difficulty determining which actions best serve the purpose and interests of each party to the issue, or which issues, if any, must be regarded as fundamental obligations. For nurses to provide patient care within an ethical framework, clinical practitioners need (1) knowledge of basic rights and ethical principles; (2) conceptual models as ways of thinking about ethical dilemmas; and (3) opportunities to explore and resolve clinical dilemmas. PMID- 8220367 TI - Values: a guiding force. AB - This article discusses the concept of values and the roles of values in the ethical decision-making process. The acquisition of values and the role of different types of values are explored. A model is presented to illustrate the nature of values as a guide to behavior. Finally, the role and impact of the individual values systems of health care professionals and patients are identified as essential ingredients in the resolution of ethical dilemmas. PMID- 8220368 TI - Dilemmas of moral distress: moral responsibility and nursing practice. AB - The experience of moral distress can be distinguished from the experience of moral dilemmas. In moral distress, a nurse knows the morally right course of action to take, but institutional structure and conflicts with other co-workers create obstacles. A nurse who fails to act in the face of obstacles also may have reactive distress in addition to the initial distress. Both kinds of distress pose dilemmas about individual and collective moral responsibility. Coping with these dilemmas effectively requires taking at least some successful actions to resolve distress. PMID- 8220369 TI - Nursing ethics: the role of caring. AB - This article contrasts two popular approaches to nursing ethics: the principle based approach and the care perspective. The care perspective is situated within the general schema of ethical theory and described. Its contributions to nursing and clinical ethics are highlighted, as are the challenges it poses to nursing practice, education, and research. The author concludes that the caring perspective provides an orientation to persons that grounds professional relationships and ethics in all of the helping professions. As such, it provides an insufficient basis for establishing a distinct theory of nursing ethics. PMID- 8220370 TI - Maternal-fetal health: ethical issues. AB - Modern medical technology has given us the ability to directly observe the fetus and its state of health. This ability has allowed the fetus to be newly individuated and has supported what often are called conflicts between the fetus and the pregnant woman. This article examines the nature of some of these conflicts and offers support for ethical theories and principles that assume that the pregnant woman is the appropriate decision maker for treatment involving her body and that if she is given support and comprehensible information, her decisions will be in the best interests of her family. PMID- 8220371 TI - Controversies in the resuscitation of infants of borderline viability. AB - Advances in perinatal technology have led to a preponderance of ethical dilemmas regarding the resuscitation of extremely preterm infants weighing between 500 and 750 grams. Although a review of the literature indicates poor outcomes in many of these infants, an equal number of studies documenting positive outcomes has been reported. A point/counterpoint format is used to discuss the issues related to the borderline viable infant. Strategies for resolution are formulated based on the issues of concern. Prevention of preterm birth, discussion of the resuscitation plan before delivery and initial resuscitation with the option to withdraw treatment are critical solutions to consider. Additional strategies include the establishment of definitive care guidelines and a standardized definition of quality of life. Other options worthy of consideration are discussed. PMID- 8220372 TI - Human fetal tissue: ethical implications for use in research and treatment. AB - Research using human fetal tissue is well established in biomedical science and indicates promising results in clinical transplantation for some diseases. Because the most optimal tissue for use in transplantation is obtained from fetuses resulting from elective abortions, this technology provokes ethical controversy. Societal concern about the ethical feasibility of human fetal tissue transplantation research (HFTTR) culminates with its investigative use in the treatment of Parkinson's disease. Reflective of such concern in the United States was the 1988 ban on federal funding for HFTTR using tissue obtained from electively terminated abortuses and the establishment of the HFTTR Panel. Considerations generating ethical debate about HFTTR include the moral status of the fetus, who should consent to use of fetal tissue in transplantation research, and issues related to complicity in, and legitimization of, abortion. The moratorium on federal funding for HFTTR has been lifted, but ethical issues and societal concerns remain unresolved. PMID- 8220373 TI - Decision making in neonatal intensive care: a collaboration of parents, physicians, and nurses. AB - Standards for decision making in the newborn intensive care unit are discussed, and the implications for increasing involvement of parents in this process is described. Nursing implications are specifically addressed. PMID- 8220374 TI - When pregnant patients refuse interventions. AB - Good communication between clinician and pregnant patients should avert most decision-making conflicts. Pregnant women may legitimately refuse prenatal screening procedures in view of the limited follow-up options. They also may choose alternatives to most standard obstetric interventions; clinical studies raise questions about the necessity of these interventions. A well-informed woman may refuse cesarean delivery in most situations: predictions of harm are highly uncertain, and she would be asked to accept risk and harm for the sake of another. However, in exceptional situations in which harm to the fetus is nearly certain and vaginal delivery also endangers the woman, the harm-to-others principle limits autonomy, and coercion may be ethically justifiable. PMID- 8220375 TI - Nurse participation in ethical decision making in the clinical setting. AB - Nurses, in their day-to-day practice, are required to combine clinical expertise with skill in moral judgment. Because of the nurse's unique relationship with the patient and a collaborative practice with the physician, the nurse often is at the forefront of identifying ethical dilemmas. In addition to identification of the ethical dilemma, the nurse often actively participates in the decision-making process. Ethical decision-making models bear some resemblance to the nursing process. The nurse plays an active role in each step of assessment, planning, implementation, and evaluation. An increasing number of nurses are formally participating in ethical decision making as a member of hospital ethics committees. The three primary tasks of these committees are: (1) education; (2) policy development; and (3) case consultation. Nursing ethics committees also are being developed to address issues specific to nursing, such as nurse staffing ratios and allocation of nursing resources. Nurses can use ethical rounds or retrospective case studies to perpetuate the study of ethics at the bedside. PMID- 8220376 TI - Environments that support ethical nursing practice. AB - Creating an ethical work environment in a health care organization is both necessary and difficult. In the process of providing care, nurses often make decisions with ethical implications. This decision making is enhanced when the work environment supports an ethical approach. Nursing can implement strategies to support ethical decision making. PMID- 8220377 TI - Ethical issues in conducting clinical nursing research. AB - It frequently is assumed that research is being conducted in an ethical manner. Although this usually is the case, the approaches used to assure an ethical approach are not explicitly described in research proposals, protocols, presentations, or manuscripts. This paper explicates the ethical issues related to conducting clinical nursing research. Ethical principles and the problems of scientific misconduct are presented. Rights of human subjects and rights of special subjects are discussed, and practical points about the conduct of ethical research are summarized. PMID- 8220378 TI - Identity, metaphors, and power. AB - Nurses may often evaluate their identities by asking questions such as "Who is the perinatal nurse? Accountable professional or institutional employee?" The author analyzes this effort in terms of the metaphors reflected by these questions as they may or may not accurately describe nurses' circumstances of powerlessness and powerfulness. The author suggests ways nurses may improve their ethical reflection by changing metaphors and assuring continuing sedation in individual, professional, and institutional contexts. PMID- 8220379 TI - Ethical reflection and resolution. AB - Resolution of ethical issues requires critical thinking and problem solving skills. This article reviews the professional code of ethics for nurses and decision-making frameworks as guides to assist nurses in becoming active participants in the process of ethical reflection. PMID- 8220380 TI - Evaluating research for clinical practice. A guide for practitioners. AB - This has been only a brief treatment of the topic, but one should note that research is an integral part of our clinical practice. If it were not for research our profession would remain static because our understanding of communicative disorders would not change. Instead, there has been a research commitment that has greatly increased our knowledge base. One only need look at the advances in assessment/treatment and the diversity in scope of practice to appreciate research. A profession well grounded in research is a profession that will continue to meet the challenges of the future. We need a strong research base to improve our services to communicatively handicapped persons, and practitioners must be active consumers of this research. The clinician and researcher share a common ground and must communicate with each other (Ringel, 1972). In practice, the speech-language pathologist needs to have a working knowledge of research, since she/he must continually deal with a variety of clinical problems. New tests and measurement procedures, treatments and other critical issues of the profession are subject to experimental scrutiny. It is up to the practitioner to critically examine an issue and then make a rational decision. Moll (1983) has indicated that rational clinical decisions are made on the basis of research and current clinical practice. There is no "cookbook" approach to utilizing research, but there are things that speech/language pathologists can do. First, one must read the literature and interpret the data. If research is to be utilized, make note of its success or lack of success.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8220381 TI - The challenge of interpreting test scores. AB - In summary, it is clear that the practicing speech-language pathologist needs to demonstrate a working knowledge of some of the basic principles of psychometric measurement in order to effectively interpret the results of commonly employed speech and language tests. It is important that the SLP is familiar with the process used for standardization of tests, as well as the difference between norm referenced and criterion-referenced tests. It is also critical that the SLP be aware of issues related to validity and reliability, as well as various types of scores associated with tests. While a background in statistics is helpful, it should be noted that the manual that accompanies each standardized test generally includes definitions, explanations, and conversion tables designed to assist the SLP in administering and interpreting the results. Careful study of the manual and a review of any questionable items via an appropriate textbook should assist the SLP in the literal interpretation of test results. In addition to the information obtained from standardized testing, it is also important to consider results of observation of the client and informal testing in order to accurately characterize speech and language behavior. PMID- 8220382 TI - Interpretation of speech science measures. AB - There are a variety of objective measures that can aid in diagnosis, selection of goals for therapy, and measurement of progress. Much of the instrumentation that is necessary to perform these measures is available for use in microcomputers, so it is within the budgets of most clinics and school systems. Although the measures described above are objective, the clinician must be cautious in their interpretation. A number of these measures are maximum performance tests of speech. Kent, Kent, and Rosenbek (1987) note that the database on these types of measurements is inadequate. In addition, performance is highly variable and dependent on factors such as client motivation, instructions provided, and whether the client is given practice first. For this reason, the clinician must consider standard deviations as well as means when using the normative data. The preceding review is not intended to be exhaustive, nor is it intended to provide enough information for clinicians to be able to perform these measurements. The intent is to describe the potential clinical utility of the measures and to spark the interest of clinicians so they will persue the matter further. It is also not the intent of this article to encourage clinicians to stop using perceptual judgments in the clinic. Pannbacker and Middleton (1990) advocate the use of both perceptual and objective measures in assessing velopharyngeal insufficiency; however, these combined measures should be considered in the diagnosis of any speech disorder. Ultimately, it is the degree to which speech sounds deviant to a naive listener that determines whether an individual's speech is a problem. PMID- 8220383 TI - Screening measurements and procedures. Exemplified by an identification audiometry program. AB - To summarize, an effective procedure in audiometric screening may be using skilled testers to screen 1, 2, and 4 kHz at 20 dBHL (with oto immittance measures) on all students up to and including grade 3, 9th and 12th year high school students, and high-risk groups including those repeating a grade, having a history of recurrent middle ear disease, having speech and/or language problems, known to participate in high noise activities, for example, guns, dirt bikes, or model planes, and those failing previous screenings. Testing is done in a quiet, nondistracting environment, with each person tested individually, although instructions may be given to small groups. Any person not responding to one or more of the stimuli is rescreened. All failing the rescreening at any frequency in either ear are referred to an audiologist. Progress is monitored to ensure that the student is seen by an audiologist and that any audiological recommendations are followed. Screening procedures such as oto immittance measures and audiometric screening are effective identification procedures used in combination by skilled persons. When follow-up procedures are adequate, the program can work effectively in ensuring help for those with auditory problems. In addition, such programs can prevent many of these problems. The general principles of screening discussed earlier are applicable to identification of a wide variety of conditions including disordered speech, language, and hearing. Application of these principles will result in realization of identification objectives which are both pragmatic and quantifiable. PMID- 8220384 TI - The use of single-subject designs in clinical practice. PMID- 8220385 TI - The role of statistics in clinical speech-language pathology and audiology. PMID- 8220386 TI - The myotropic peptides of Locusta migratoria: structures, distribution, functions and receptors. AB - The search for myotropic peptide molecules in the brain, corpora cardiaca, corpora allata suboesophageal ganglion complex of Locusta migratoria using a heterologous bioassay (the isolated hindgut of the cockroach, Leucophaea maderae) has been very rewarding. It has lead to the discovery of 21 novel biologically active neuropeptides. Six of the identified Locusta peptides show sequence homologies to vertebrate neuropeptides, such as gastrin/cholecystokinin and tachykinins. Some peptides, especially the ones belonging to the FXPRL amide family display pleiotropic effects. Many more myotropic peptides remain to be isolated and sequenced. Locusta migratoria has G-protein coupled receptors, which show homology to known mammalian receptors for amine and peptide neurotransmitters and/or hormones. Myotropic peptides are a diverse and widely distributed group of regulatory molecules in the animal kingdom. They are found in neuroendocrine systems of all animal groups investigated and can be recognized as important neurotransmitters and neuromodulators in the animal nervous system. Insects seem to make use of a large variety of peptides as neurotransmitters/neuromodulators in the central nervous system, in addition to the aminergic neurotransmitters. Furthermore quite a few of the myotropic peptides seem to have a function in peripheral neuromuscular synapses. The era in which insects were considered to be "lower animals" with a simple neuroendocrine system is definitely over. Neural tissues of insects contain a large number of biologically active peptides and these peptides may provide the specificity and complexity of intercellular communications in the nervous system. PMID- 8220387 TI - The mosquito dihydrofolate reductase gene functions as a dominant selectable marker in transfected cells. AB - An Aedes albopictus dihydrofolate reductase gene was used to construct two chimeric DNA vectors that functioned as dominant selectable markers in transfected, wild type mosquito cells. Stably transformed clones were recovered after 10-15 days in the presence of selective medium containing 1 microM methotrexate. The transformed clones contained an estimated 100-500 copies of transfected DNA per nucleus. Combined data from Southern blots and in situ hybridization to metaphase chromosomes indicated that transfected DNA was likely integrated into chromosomes both as repeated structures and as randomly integrated single copy molecules, with minimal rearrangement of coding sequences. Transfected DNA was stably maintained under selective conditions, but in some cases was lost when cells were maintained for prolonged periods in the absence of methotrexate. These observations provide a general framework for further development of stable gene transfer systems for mosquito cells in culture. PMID- 8220389 TI - Induction of antibacterial protein synthesis by soluble peptidoglycan in isolated fat body from larvae of the silkworm, Bombyx mori. AB - Synthesis and secretion of bactericidal protein (cecropin) and lysozyme were induced by soluble peptidoglycan fragments (SPG) from Escherichia coli in a culture of fat body from Bombyx mori larvae. The rate of the secretion by fat body increased as a function of SPG concentration added to the culture medium. The induction of bactericidal activity was specific for peptidoglycan of a particular structure. Thus, SPG from Micrococcus luteus was 500-times less potent than E. coli SPG, and various glucans and peptides structurally related to peptidoglycan were all ineffective as elicitor. These results support the hypothesis that bacteria invading the haemocoel have to be partially degraded to generate peptidoglycan fragments as a signal molecule, which subsequently acts on a receptor on fat body cells and induces antibacterial protein synthesis. PMID- 8220388 TI - Expression of a Bombyx cytoplasmic actin gene in cultured Drosophila cells: influence of 20-hydroxyecdysone and interference with expression of endogenous cytoplasmic actin genes. AB - The expression of the Bombyx cytoplasmic actin A3 gene and its response to 20 hydroxyecdysone are studied after transfection in hormone responsive Drosophila cells and are compared to the expression of homologous resident genes. The host cells accumulate correct transcripts of the Bombyx gene in a gene dosage dependent way. The relative amount of endogenous cytoplasmic actin mRNAs is decreased in transfected cells, whether the transgene is integrated into the genome or not. When 20-hydroxyecdysone is added to the culture medium, the accumulation of the foreign mRNA is decreased whereas those of endogenous cytoplasmic actin transcripts are increased. These results are discussed in terms of competition for transcription and regulatory factors. PMID- 8220390 TI - Genetic analysis by DNA fingerprinting in tsetse fly genomes. AB - Genomic DNA from tsetse flies (Diptera: Glossinidae: Glossina Wiedemann) was analyzed by hybridization using the whole M13 phage as a probe to reveal DNA fingerprinting (DNAfp) profiles. Intrapopulation variability, measured by comparison of DNAfp profiles of tsetse flies from a large colony of G. brevipalpis, showed a high degree of polymorphism similar to that found in other animal species. Different lines of G. m. morsitans, G. m. centralis, G. m. submorsitans, G. p. palpalis and G. p. gambiensis established from small colonies displayed less genetic variability than the G. brevipalpis population. The analysis of pedigree relationships within an inbred line of G. m. centralis conformed to a Mendelian inheritance pattern. In the pedigree presented no mutations were observed, one fragment was linked to the X chromosome, and three fragment sets were linked, but most fragments showed independent segregation. M13 revealed no characteristic DNAfp profile differences between the subgenus Glossina and the subgenus Nemorhina, but a conserved distribution pattern was found in the laboratory colonies within each subspecies. M13 also revealed line specific DNA fragments that may be useful as genetic markers to expand the present linkage map of G. m. morsitans. PMID- 8220391 TI - Weight loss and weight cycling in amateur wrestlers: implications for performance and resting metabolic rate. AB - Amateur wrestlers practice weight loss for ergogenic reasons. The effects of rapid weight loss on aerobic performance are adverse and profound, but the effects of anaerobic performance are equivocal. Anaerobic performance--strength and power--may be the most relevant type of performance to the wrestler. Maintenance of or even small decrements in anaerobic performance may translate into improvements in performance relative to the weight class, the factor by which wrestlers are matched for competition. During the recovery period between the official weigh-in and competition, wrestlers achieve at least partial nutritional recovery, which appears to benefit performance. Successive bouts of (a) weight loss to make weight and (b) recovery for performance lead to weight cycling. There is speculation that weight cycling may contribute to chronic glycogen depletion, reductions in fat-free weight, a decrease in resting metabolic rate, and an increase in body fat. The latter two would augment the difficulty of losing weight for subsequent weigh-ins. Most research indicates that the suppressed resting metabolic rate with weight loss in wrestlers appears to be transient, but subsequent research is needed for confirmation. PMID- 8220392 TI - Zinc loss in sweat of athletes exercising in hot and neutral temperatures. AB - Zinc (Zn) loss from sweat of 9 male and 9 female athletes exercising under hot (35 degrees C, HE) and neutral (25 degrees C, NE) conditions was examined. Subjects exercised at 50% VO2max on a cycle ergometer for 1 hr during each trial. Cell-free sweat samples were analyzed for Zn by atomic absorption spectrophotometry. There was a significant interaction of time, gender, and temperature for whole-body sweat rates (WBSR). WBSR for males were higher during both trials and at each time. WBSR from the second half of exercise were higher than those from the first half for both sexes and temperature conditions. Sweat Zn concentration was higher in the NE than in the HE, but when the sweat rates were included, the rate of Zn loss was no different between HE and NE. Zn concentration of the sweat for the first half of exercise was over twice that of the second half. Sweat Zn concentration of the men was no different than that of the women; however, due to greater sweat rate, men had significantly higher Zn losses. Although total Zn losses are estimated to be relatively low compared to the RDA, exercise at moderate intensities may increase surface Zn losses. PMID- 8220393 TI - Exercise training and dietary carbohydrate: effects on selected hormones and the thermic effect of feeding. AB - To determine relationships among dietary carbohydrate, aerobic exercise training, the thermic effect of food (TEF), and hormonal responses to feeding, 8 trained and 7 sedentary men consumed diets providing 15, 45, or 75% of energy as carbohydrate for 5 days. On Day 6, metabolic rate was measured before as well as 30, 60, 90, and 120 min after an 868-kcal liquid test breakfast. Blood was sampled hourly during Day 5 and during each metabolic rate measurement. The trained group had a larger TEF (40 +/- 2.4 vs. 31 +/- 3.0 kcal/2 hrs), greater insulin sensitivity, and greater plasma prolactin and cortisol levels. As carbohydrate in the treatment diet increased, carbohydrate utilization and thyroid stimulating hormone were higher and thyroxine was lower, but TEF was not significantly different. After the test meal, trained individuals had a higher TEF but the carbohydrate content of the treatment diet did not influence TEF. PMID- 8220394 TI - Low-dose amino acid supplementation: no effects on serum human growth hormone and insulin in male weightlifters. AB - Using a double-blind, crossover protocol, we studied the possible effects of a 4 day combined L-arginine, L-ornithine, and L-lysine supplementation (each 2 g/day, divided into two daily doses) on 24-hr level of serum human growth hormone (hGH) and insulin in 11 competitive weightlifters, ages 19 to 35 yrs. Three similar daily hGH peaks, seemingly preceded by a decrease in serum insulin concentration, were found during both amino acid and placebo supplementation. Supplementation did not affect the physiological variation of serum hGH concentration (treatment and treatment x time interaction: p = 0.43-0.55). Analogously, serum insulin levels were not higher after amino acid supplementation. Therefore the ergogenic value of low-dose oral amino acid supplementation in increasing hGH or insulin secretion seems questionable. PMID- 8220395 TI - Failure of commercial oral amino acid supplements to increase serum growth hormone concentrations in male body-builders. AB - Amino acids are commonly ingested as ergogenic acids in the belief that they enhance protein synthesis and stimulate growth hormone release. The aim of this study was to determine the acute effect that amino acid supplements have on serum growth hormone (GH) concentration. Seven male body-builders reported to the laboratory on four occasions after an 8-hr fast and ingested, in random order, either a placebo, a 2.4-g arginine/lysine supplement, a 1.85-g ornithine/tyrosine supplement, or a 20-g BovrilR drink. Blood was collected before each treatment and again every 30 minutes for 3 hours for the measurement of serum GH concentration. On a separate occasion, subjects had an intravenous infusion of 0.5 microgram GH-releasing hormone.kg-1 body weight to confirm that GH secretory response was normal. The main finding was that serum GH concentrations were not altered consistently in healthy young males following the ingestion of the amino acid supplements in the quantities recommended by the manufacturers. PMID- 8220396 TI - Endocrine and performance responses to high volume training and amino acid supplementation in elite junior weightlifters. AB - To examine the effects of 1 week of high volume weightlifting and amino acid supplementation, 28 elite junior male weightlifters received either amino acid (protein) or lactose (placebo) capsules using double-blind procedures. Weightlifting test sessions were performed before and after 7 days of high volume training sessions. Serum concentrations of testosterone (Tes), cortisol (Cort), and growth hormone (GH) as well as whole blood lactate (HLa) were determined from blood draws. Lifting performance was not altered for either group after training, although vertical jump performance was not altered for either group after training, although vertical jump performance decreased for both groups. Both tests elicited significantly elevated exercise-induced hormonal and HLa concentrations. Significant decreases in postexercise hormonal and HLa concentrations from Test 1 to Test 2 were observed for both groups. Tes concentrations at 7 a.m. and preexercise decreased for both groups from Test 1 to Test 2, while the placebo group exhibited a decreased 7 a.m. Tes/Cort. These data suggest that amino acid supplementation does not influence resting or exercise induced hormonal responses to 1 week of high volume weight training, but endocrine responses did suggest an impending over-training syndrome. PMID- 8220397 TI - Effects of preexercise candy bar ingestion on glycemic response, substrate utilization, and performance. AB - This study examined the effects of preexercise candy bar ingestion on glycemic response, substrate utilization, and performance in 8 trained male cyclists. The cyclists randomly ingested one large milk chocolate bar (1CB), two large milk chocolate bars (2CB), or a placebo (P) 30 min prior to a 90-min cycle ride at 70% VO2max followed by a 33-W increase every 2 min until exhaustion (approximately 10 min). Glucose decreased after 15 min of exercise but returned to preexercise values by 30 min of exercise. Glucose concentration for 2CB was significantly higher than for P and 1CB at exhaustion. Insulin concentration increased in response to 1CB and 2CB and returned to preexercise values within 15 min of exercise. No significant differences were noted for free fatty acid (FFA) concentrations, lactate concentrations, respiratory exchange ratio, total carbohydrate oxidation, or estimated fat and carbohydrate oxidation rates. Time to exhaustion was similar among the groups. The results suggest that the transient lowering of blood glucose observed with preexercise milk chocolate bar ingestion 30 min prior to exercise may not cause major metabolic perturbations that impair athletic performance in trained athletes performing moderately intense cycle exercise. PMID- 8220398 TI - On dancers and diet. AB - Dancers exhibit compliance problems in adopting advice from nutrition experts. Examination of the situation reveals an inherent culture clash between dancers and nutrition authorities. Dancers need safe methods of achieving an ultralean physique, but the recommendations of most nutritionists do not fit dancers' requirements. This manuscript is intended to provide the nutrition professional with insight into the dancer's needs and cultural/professional perspective on dieting. Dietary problems/disorders that are common among dancers are reviewed. Both general and specific recommendations are made for advising dancers and for designing their diets. PMID- 8220399 TI - The analysis of small-sample multivariate data with applications in clinical trials. AB - This article discusses statistical methods for the analysis of multivariate data arising in clinical trials involving a small number of subjects randomly assigned to one of several treatment groups. Possible violations of traditional assumptions such as variance homogeneity and normality of errors are often dealt with by carrying out the statistical analysis using strategies such as transforming the data or applying nonparametric procedures. Multivariate nonparametric tests provide a realistic alternative for analyzing such data. We present a permutation procedure for analyzing data arising in randomized experiments. PMID- 8220400 TI - Planning survival studies to compare a treatment to an active control. AB - Rubinstein et al. presented a procedure for determining the required duration of accrual for a clinical trial comparing the survival distributions of two treatments using a classical hypothesis testing formulation. Here their testing procedure is modified in two ways. First, the asymptotic variances used in computation of the probabilities of type I and type II errors are based on the values of the parameters specified by the null and alternative hypotheses, respectively. Second, the null hypothesis is modified for situations where it is desired to show that the experimental treatment is better or not much worse than the control. PMID- 8220401 TI - Sample size determination using an interim analysis. AB - Interim analyses are often employed to terminate comparative clinical trials for ethical or economic reasons when the evidence indicates that one treatment is superior to the other. Here an interim analysis is proposed for the situation where a one-sided test is to be performed. The proposed interim analysis consists of a one-sided test to terminate the clinical trial if it appears that the null hypothesis of interest is true. By noting that incorporation of a single interim analysis is similar to the two-stage procedure used for constructing a test procedure with power independent of the unknown variance, it also includes estimation of the variance, which can be used to control the power of the test if the trial is not terminated. Various properties of this two-stage procedure and derivation of the constants needed for its implementation are presented. PMID- 8220402 TI - Statistical considerations for cross-sectional data relating to tracheal reconstruction over time. AB - Complementary statistical analyses are performed on data concerning tracheal reconstruction in rats. The principal response criterion is vessel area as defined by the area of a graft onto the trachea covered by blood vessels. Postoperatively, this vessel area changes in a nonlinear fashion over time. Starting at 0% immediately postoperation, the vessel area increases to a peak and then sharply decreases to a certain level at which it remains. A total of 64 independently observed cross-sectional pairs (postop day, vessel area) are distributed among four treated groups. Analysis consists of two-way analysis of variance and piecewise linear regression under the usual assumptions of normality and variance homogeneity. Other analyses that relax these assumptions are also considered; treatment differences are established by nonparametric tests, and a quasi-likelihood analysis of the piecewise linear regression model is applied under the assumption of a binomial-like variance function. The resulting fit of the normal-theory-based piecewise linear model is compared to that of a nonlinear model whose shape is that of a gamma function integrand. PMID- 8220403 TI - A log-normal model for individual bioequivalence. AB - A log-normal model is developed for testing pi 1, the probability that a subject's response will fall within given bioequivalence limits. The model is a parametric analog of Anderson and Hauck's TIER rule. Confidence intervals and hypothesis tests are derived. Statistical power is compared with the that of the TIER rule. The probability of demonstrating mean bioequivalence is shown to greatly exceed that of showing individual bioequivalence. PMID- 8220404 TI - Structure-activity maps for visualizing the graph variables arising in drug design. AB - Structure-activity problems are characterized by the topological and topographical character of the structural information determining the activity. Traditional statistical methodology requires that this predictive information be mapped to a vector space. To circumvent this vexing conversion of structural information to vector form, the edge-deletion metric is defined on the space of chemical graphs that defines the topology of the molecules. This paper proposes structure-activity maps and transformation-effect maps for directly visualizing the structure-activity relationships. The maps are illustrated using the hypotensive activities of clonidine analogs and the sweet taste of Perillartine analogs. PMID- 8220405 TI - Confidence intervals versus p-values for interpretation of clinical trial results: introduction. AB - The following three papers summarize the presentations at a Society for Clinical Trials annual meeting session on the relative merits of estimation versus testing for analysis of randomized clinical trials. By design, randomized clinical trials have internal validity. Whether they also possess quantitative external validity- generalizability of effect size to some population represented by the trial subjects--is one of the main points of disagreement among the three authors. It may be unrealistic to expect a resolution that applies across the wide variety of therapeutic areas and clinical trial goals. Extrapolation from clinical trial to clinical practice is often endorsed in connection with large trials having loose entry criteria and focusing on an objective, clearly meaningful clinical endpoint. By contrast, the relevance of estimates of effect size is less clear in the case of many clinical trials conducted in the course of drug development. PMID- 8220406 TI - Why confidence intervals are useful tools in clinical therapeutics. PMID- 8220407 TI - Statistical estimates and clinical trials. AB - Statistical estimates and significance tests address distinct (but related) questions using the same data. Point estimates and confidence intervals of differences are statistical estimates that address: "How LARGE is the difference in the population of interest?" A significance test addresses the question: "How LIKELY was the difference to have occurred by chance?" Because p-values deal with the existence of a real nonzero difference between treatments but not the size of that treatment difference, they cannot be used to assess clinical (practical) significance. A confidence interval is a range of values used to infer both the size of a difference and the uncertainty of the estimate. Examples illustrate how confidence intervals help us assess both the clinical significance and the statistical significance of an observed difference. The point estimate is the outcome difference actually observed in the study sample; it is also the best single-number estimate of the unknown difference in the sampled population. Point estimates, confidence intervals, and p-values extract complementary information from study data and should all be reported for major results. PMID- 8220408 TI - Confidence intervals and controlled clinical trials: incompatible tools for medical research. AB - The probabilistic rationale for statistical design and analysis of clinical trials is random assignment. While arithmetic and mathematical formulations may be identical to those used with random samples, we should not indiscriminately borrow tools from survey sample methods. Specifically, the confidence interval should be used sparingly, if at all. Observations have an internal validity, within the clinical trial, with no basis for claims of quantitative external generalizability. Confidence intervals encourage an unnecessary dependence on statistical analysis when the careful design should allow the data to speak for itself. Confidence intervals encourage a statistical focus and statistical conclusions that ignore scientific context and misrepresent relationships among results from related research. The clinician is presented with information about population parameters when facing confidence intervals. These do not address questions about treatment and prognosis of an individual patient. Confidence intervals are particularly distracting when a clinical trial has failed to produce anticipated results. The clinical trial is the model research tool for clinical medical research, founded on randomization. The confidence interval is a statistical tool for parameter estimation based on population sampling concepts. These tools are incompatible. PMID- 8220409 TI - Baseline distribution and conditional size. AB - Analytic results are presented for the effect of baseline distribution on the conditional size of various hypothesis or significance tests of treatment that may be performed in a two-group trial. These analytic results may be substituted for results achieved via simulation and previously published in this journal. PMID- 8220410 TI - Isometric hip abductor strength following total hip replacement and its relationship to functional assessments. AB - Despite the rehabilitative emphasis on hip abductor strength following total hip replacement (THR), it is unclear how muscular strength is related to function. The purposes of this study were to examine changes in hip abductor strength during the first 6 months following THR and to determine the relationship between hip abductor strength and functional performances. Forty-three patients (mean age 64 +/- 7 years) completed strength assessments before surgery and at 1, 6, 12, and 24 weeks after surgery, and functional assessments before surgery and at 12 and 24 weeks after surgery. Both hip abductor strength and functional performance were significantly improved at each assessment (p < 0.01). The correlation between isometric hip abductor torques and the distance walked in 6 minutes was modestly high (r = 0.48-0.51; p < 0.01). This study provides baseline data for isometric hip abductor strength that can be used comparatively to assess patient progress and to help set clinical goals. Although strength is related to function, isometric measurements of strength should not be relied upon as the sole predictors of function in patients who have undergone THR. PMID- 8220411 TI - The effects of foot orthotics on the EMG activity of selected leg muscles during gait. AB - Foot orthotics have been successfully used to treat muscular overuse leg injuries in athletes. The purpose of this study was to examine the effects of foot orthotics on the electromyographic (EMG) activity of the tibialis anterior, peroneus longus, and gastrocnemius muscles during walking. Ten volunteers with leg symptoms resulting from compensatory subtalar joint pronation were fitted with foot orthotics. The duration of tibialis anterior EMG activity following heel strike and the average EMG activity of the tibialis anterior, peroneus longus, and gastrocnemius muscles were collected with surface electrodes. Comparisons were made between the orthotic and nonorthotic conditions. A t-test for nonindependent samples with a significance level of p < 0.05 was used for data analysis. There was a statistically significant increase in the duration of tibialis anterior activity following heel strike in the orthotic condition. There were no significant differences in the average EMG activity for any of the three muscles between the orthotic and the nonorthotic conditions. This study suggests that foot orthotics had minimal effects on the muscles studied and that further research is necessary to determine the effectiveness of orthotics on the EMG activity of other leg muscles. PMID- 8220412 TI - The effects of assistive devices on the oxygen cost, cardiovascular stress, and perception of nonweight-bearing ambulation. AB - Nonweight-bearing ambulation with the aid of an assistive device is often prescribed in the clinical setting. Little is known about the oxygen cost, cardiovascular stress, and perception of effort of these devices when applied to the same sample of subjects. Therefore, the present study compared the oxygen cost, cardiovascular stress [measured by heart rate (HR), blood pressure (BP) responses, and rate pressure product (RPP)], and perception of effort [measured by ratings of perceived exertion (RPE)] of unassisted ambulation (UA), nonweight bearing ambulation using axillary crutches (AC), a standard walker (SW), and a wheeled walker (WW). Nine female subjects ambulated at self-selected velocities for 7 minutes during each ambulation mode. Oxygen consumption, HR, BP, and RPEs were obtained. As expected, UA resulted in the lowest VO2 (11.2 +/- 1.4 ml/kg.min 1) and greatest velocity (1.24 +/- 0.27 m/sec). Results also indicated that AC ambulation resulted in lower oxygen consumption per meter (0.4 +/- 0.1 ml/kg.m-1) and greater velocity (0.74 +/- 0.18 m/sec) than either SW ambulation (0.6 +/- .1 ml/kg.-1, 0.39 +/- 0.09 m/sec) or WW ambulation (0.6 +/- .1 ml/kg.m-1, 0.40 +/- 0.12 m/sec) (p < .05). No differences were observed among assisted ambulation modes for HR, BP responses, RPP, or RPE values. Because patients typically ambulate for a set distance (rather than a set time) and because the oxygen cost per unit distance was lowest for AC, it is suggested that, when possible, AC should be prescribed for non-weight-bearing ambulation. PMID- 8220414 TI - Reliability of open and closed kinetic chain subtalar joint neutral positions and navicular drop test. AB - Subtalar joint (STJ) measurements are commonly made in the clinic to assess foot and ankle positions because of the high incidence of lower extremity dysfunctions. The purposes of this study were to investigate the intratester and intertester reliability of the open kinetic chain subtalar joint neutral (OKC STJN) and closed kinetic chain subtalar joint neutral (CKC STJN) positions and the navicular drop test (NDT). Two inexperienced testers performed repeated measurements on 15 subjects (N = 30 feet) during two testing sessions. Intratester and intertester reliability (ICC 1,1) and standard error of measurement (SEM) were determined for each dependent variable. For OKC STJN, the intratester ICC values were .06 and .27, and the intertester ICC value was .00. The intratester SEM values were 1.81 and 2.29 degrees, and the intertester was 2.51 degrees. The CKC STJN intratester ICC values were .14 and .18, with SEM values of 2.46 and 2.40 degrees. The intertester CKC ICC value was .15, with an SEM of 2.43 degrees. For the NDT, the intratester ICC values were .61 and .79, and the SEM values were 1.92 mm and 2.57 mm. The intertester ICC value was .57 and the SEM was 2.72 mm. The results reveal that both OKC and CKC STJN yield poor intratester and intertester reliability and the NDT yields poor to moderate intratester reliability and poor intertester reliability. We conclude that these foot and ankle measurements are not reliable when performed by inexperienced testers. Therefore, clinicians should practice these measurement techniques and determine their measurement error. PMID- 8220413 TI - Reliability of dynamic and isometric testing of shoulder external and internal rotators. AB - Advances in isokinetic technology allow the physical therapist to assess concentric, eccentric, and isometric muscle performance at the shoulder in various positions. Research is limited, however, on the reliability of isokinetic measurements. The purposes of this study were: 1) to determine the test-retest reliability of concentric, eccentric, and isometric muscle performance measurements of shoulder external and internal rotation in the scapular plane test position and 2) to compare this reliability between the involved and uninvolved limb of subjects with a history of unilateral shoulder pathology. Fourteen males and 10 females (17-58 years) were tested on two occasions at 1 week intervals with the Biodex isokinetic dynamometer. Peak torque, total work, and average power were recorded for concentric tests at angular velocities of 60 and 120 degrees/sec and for eccentric tests at 60 degrees/sec. Maximum average isometric torque was recorded in two positions. Means, standard deviations, and mean differences between sessions with 95% confidence intervals were calculated. Intraclass correlation coefficients (ICCs) were used to determine test-retest reliability. Isometric tests were generally most reliable (ICC = .81-.93), followed by concentric (ICC = .60-.95) and eccentric tests (ICC = .44-.92). Isokinetic and isometric reliability were usually higher for involved than uninvolved shoulders. The implication of these findings is that there appears to be greater variability with eccentric than concentric or isometric testing of shoulder rotation. Factors that possibly contributed to variability are discussed. Clinicians should recognize potential sources of testing error when obtaining isokinetic measurements for use in clinical decision-making. Further refinement of isokinetic testing protocols at the shoulder is recommended. PMID- 8220415 TI - Knee flexor-extensor strength in children. AB - Isokinetic measurements of knee flexion extension in children and adolescents are a useful means of quantifying strength. In the routine clinical situation with a unilateral problem, evaluation of the affected extremity is usually based on comparisons with the unaffected side. To interpret these results, there must be an appreciation for normal side-to-side differences. Twenty-one normal, healthy children (ages 6-16 years) were evaluated using a Cybex II isokinetic dynamometer at 90 and 240 degrees/sec. In children who were able to generate peak torque values greater than 50 ft-lbs, the side-to-side differences in peak torque averaged 11 +/- 12% (mean +/- SD). A similar amount of variability has been reported with adults. For children with whom peak torque values were less than 50 ft-lbs, the side-to-side differences were much greater (mean = 22 +/- 19%). The stronger leg was equally likely to be on the nondominant side as the dominant side. Side-to-side variability was slightly decreased if the mean of several repetitions was used for comparisons rather than comparing just the single highest peak torque values. PMID- 8220416 TI - Comparability of force measurements obtained with different strain gauge hand held dynamometers. AB - With multiple hand-held devices now available for measuring muscle strength, clinicians need to know if the measurements obtained with the different devices are comparable. This study was performed to determine the comparability of force measurements obtained with two different strain gauge hand-held dynamometers. Specifically examined to establish comparability were differences, reliabilities, and correlations between measurements obtained with the different devices. Thirty one healthy volunteers were tested with each device during a single session. The muscle groups tested isometrically were the elbow flexors, shoulder external rotators, and hip flexors. Although the magnitude of forces measured with the two dynamometers differed significantly, they demonstrated good to high reliabilities and correlations. Thus, the dynamometers should not be used interchangeably on the same patient. Either of the dynamometers, however, can be used (alone) to document muscle force production. PMID- 8220417 TI - Straight genetics. PMID- 8220418 TI - Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice [corrected]. AB - Overexpression of the gene encoding the beta-amyloid precursor protein (APP) may have a key role in the pathogenesis of both Alzheimer's disease (AD) and Down Syndrome (DS). We have therefore introduced a 650 kilobase (kb) yeast artificial chromosome (YAC) that contains the entire, unrearranged 400 kb human APP gene into mouse embryonic stem (ES) cells by lipid-mediated transfection. ES lines were generated that contain a stably integrated, unrearranged human APP gene. Moreover, we demonstrate germ line transmission of the APP YAC in transgenic mice and expression of human APP mRNA and protein at levels comparable to endogenous APP. This transgenic strategy may prove invaluable for the development of mouse models for AD and DS. PMID- 8220419 TI - LIS is more. PMID- 8220420 TI - Untwirling dirvish. PMID- 8220421 TI - A gene for familial hemiplegic migraine maps to chromosome 19. AB - Familial hemiplegic migraine is an autosomal dominant disorder of unknown pathogenesis in which the migrainous attacks are marked by the occurrence of a transient hemiplegia during the aura. While investigating CADASIL, mapped previously to chromosome 19, we observed that some patients had recurrent attacks of migraine with aura. Although the clinical and neuroimaging features of familial hemiplegic migraine differ markedly from CADASIL, we hypothesized that the same gene could be involved in the pathogenesis of both conditions. We chose two large pedigrees for linkage analysis of familial hemiplegic migraine. A maximum lod score > 8 was found with two markers that are also strongly linked to CADASIL. Multilocus linkage analysis suggested that the loci responsible for the two diseases reside within an interval of about 30 cM on chromosome 19. PMID- 8220422 TI - A mutation in the human ryanodine receptor gene associated with central core disease. AB - Central core disease (CCD) is a morphologically distinct, autosomal dominant myopathy with variable clinical features. A close association with malignant hyperthermia (MH) has been identified. Since MH and CCD genes have been linked to the skeletal muscle ryanodine receptor (RYR1) gene, cDNA sequence analysis was used to search for a causal RYR1 mutation in a CCD individual. The only amino acid substitution found was an Arg2434His mutation, resulting from the substitution of A for G7301. This mutation was linked to CCD with a lod score of 4.8 at a recombinant fraction of 0.0 in 16 informative meioses in a 130 member family, suggesting a causal relationship to CCD. PMID- 8220423 TI - Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia. AB - Central core disease (CCD) of muscle is an inherited myopathy which is closely associated with malignant hyperthermia (MH) in humans. CCD has recently been shown to be tightly linked to the ryanodine receptor gene (RYR1) and mutations in this gene are known to be present in MH. Mutation screening of RYR1 has led to the identification of two previously undescribed mutations in different CCD pedigrees. One of these mutations was also detected in an unrelated MH pedigree whose members are asymptomatic of CCD. The data suggest a model to explain how a single mutation may result in two apparently distinct clinical phenotypes. PMID- 8220424 TI - Point mutations in the c-Myc transactivation domain are common in Burkitt's lymphoma and mouse plasmacytomas. AB - We have screened the entire coding region of c-myc in a panel of Burkitt's lymphomas (BLs) and mouse plasmacytomas (PCTs). Contrary to the belief that c-myc is wild type in these tumours, we found that 65% of 57 BLs and 30% of 10 PCTs tested exhibit at least one amino acid (aa) substitution. These mutations were apparently homozygous in all BL cell lines tested and two tumour biopsies, implying that the mutations often occur before Myc/Ig translocation in BL. In PCTs, only the mutant c-myc allele was expressed indicating a functional homozygosity, but occurrence of mutations after the translocation. Many of the observed mutations are clustered in regions associated with transcriptional activation and apoptosis, and in BLs, they frequently occur at sites of phosphorylation, suggesting that the mutations have a pathogenetic role. PMID- 8220425 TI - The long [E/e] and the short [C/c] of the rhesus polymorphism. PMID- 8220426 TI - Molecular genetic basis of the human Rhesus blood group system. AB - The Rhesus (RH) blood group locus is composed of two related structural genes, D and CcEe, that encode red cell membrane proteins carrying the D, Cc and Ee antigens. As demonstrated previously, the RhD-positive/RhD-negative polymorphism is associated with the presence or the absence of the D gene. Sequence analysis of transcripts and genomic DNA from individuals that belong to different Rh phenotypes were performed to determine the molecular basis of the C/c and E/e polymorphisms. The E and e alleles differ by a single nucleotide resulting in a Pro226Ala substitution, whereas the C and c alleles differ by six nucleotides producing four amino acid substitutions Cys16Trp, Ile60Leu, Ser68Asn and Ser103Pro. With the recent cloning of the RhD gene, these findings provide the molecular genetic basis that determine D, C, c, E and e specificities. PMID- 8220427 TI - LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas. AB - We have shown previously that chromosomal translocations involving chromosome 3q27 and immunoglobulin gene regions are the third most common specific translocations in non-Hodgkin's lymphoma (NHL). We now report the isolation of a gene that is disrupted in two cases by t(3;14) and t(3;4) translocations. The gene (LAZ3) encodes a 79 kDa protein containing six zinc-finger motifs and sharing amino-terminal homology with several transcription factors including the Drosophila tramtrack and Broad-complex genes, both of which are developmental transcription regulators. LAZ3 is transcribed as a 3.8 kb message predominantly in normal adult skeletal muscle and in several NHL carrying 3q27 chromosomal defects. We suggest that it may act as a transcription regulator and play an important role in lymphomagenesis. PMID- 8220428 TI - The insulin-like growth factor type-2 receptor gene is imprinted in the mouse but not in humans. AB - In mouse, four genes have been found to undergo genomic imprinting resulting in differential expression of maternally and paternally inherited alleles. To determine whether the cognate genes are also subject to imprinting in humans, we have studied allele-specific expression patterns of insulin-like growth factor 2, IGF2-receptor and H19 in human fetal and adult tissues. In keeping with previous findings in mice, our results indicate that in human fetal tissues the paternal H19 alleles is inactive. IGF2 is monoallelically expressed in various tissues but surprisingly not in adult human liver. The human IGF2R gene, another classic example of imprinting in mice, was found to be expressed from both alleles. We provide the first direct evidence for differential imprinting in the human and murine genome. PMID- 8220430 TI - Mutations of PAX3 unlikely in Waardenburg syndrome type 2. PMID- 8220429 TI - A type X collagen mutation causes Schmid metaphyseal chondrodysplasia. AB - The expression of type X collagen is restricted to hypertrophic chondrocytes in regions undergoing endochondral ossification, such as growth plates. The precise function of type X collagen is unknown but the tissue-specific expression prompted us to examine the gene in hereditary disorders of cartilage and bone growth (osteochondrodysplasias). We have identified a 13 base pair deletion in one type X collagen allele segregating with autosomal dominant Schmid metaphyseal chondrodysplasia in a large Mormon kindred (lod score = 18.2 at theta = 0). The mutation produces a frameshift which alters the highly conserved C-terminal domain of the alpha 1(X) chain and reduces the length of the polypeptide by nine residues. This mutation may prevent association of the mutant polypeptide during trimer formation, resulting in a decreased amount of normal protein. PMID- 8220431 TI - Anticipation in spinocerebellar ataxia type 2. PMID- 8220432 TI - Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone. AB - We report a woman with primary amenorrhoea and infertility associated with an isolated deficiency of pituitary follicle-stimulating hormone (FSH), but normal luteinizing hormone (LH) secretion. Ovulation was induced by administration of exogenous FSH and resulted in a successful pregnancy. Sequence analysis of the FSH beta-subunit gene indicated that she is homozygous for a two nucleotide frameshift deletion in the coding sequence. Her mother and son are heterozygous for this mutation. This deletion results in an alteration of amino acid codons 61 86 followed by a premature termination codon. The predicted truncated beta subunit peptide lacks regions which are important for association with the alpha subunit and for binding to and activation of the FSH receptor. Abnormalities of FSH structure or function might be an under recognised but treatable cause of infertility. PMID- 8220433 TI - Mapping loci influencing the persistence of Theiler's virus in the murine central nervous system. AB - Inbred strains of mice differ greatly in their susceptibility to the demyelinating disease caused by Theiler's Murine Encephalomyelitis Virus. In this murine disease, which is an animal model for the study of multiple sclerosis, demyelination depends on the persistent infection of the central nervous system. Previous studies identified a locus in the H-2D region of the major histocompatibility complex which controls susceptibility to the persistent infection, and also showed that other loci are involved. In order to identify these loci, we screened the genome of a set of backcross animals with a combination of polymorphic microsatellites and restriction enzymes sites. We now show that viral persistence is also controlled by a locus close to Ifg on chromosome 10 and possibly by a locus near Mbp on chromosome 18. PMID- 8220434 TI - Mouse minisatellite mutations induced by ionizing radiation. AB - The detection of changes in germline mutation rate in human populations remains extremely difficult. Estimating the genetic hazards of radiation and other mutagens in humans therefore depends on extrapolation from experimental systems. Because of the very low frequency of spontaneous mutation at most loci, enormous samples are required to detect increases of mutation rate. A very high rate of spontaneous germline mutation altering the length of minisatellite loci has been found in human populations and therefore this system might be useful for detecting induced mutations in relatively small samples. Here we present evidence that minisatellite mutation rate in mice is increased by low doses of ionizing radiation. PMID- 8220435 TI - Isolation and characterization of APLP2 encoding a homologue of the Alzheimer's associated amyloid beta protein precursor. AB - Familial Alzheimer's disease (FAD) is a genetically heterogeneous disorder that includes a rare early-onset form linked to mutations in the amyloid b protein precursor (APP) gene. Clues to the function of APP derive from the recent finding that it is a member of a highly conserved protein family that includes the mammalian amyloid precursor-like protein (APLP1) gene which maps to the same general region of human chromosome 19 linked to late-onset FAD. Here we report the isolation of the human APLP2 gene. We show that APLP2 is a close relative of APP and exhibits a very similar pattern of expression in the brain and throughout the body. Like APP, APLP2 contains a cytoplasmic domain predicted to couple with the GTP-binding protein G(o) indicating that it may be an additional cell surface activator of this G protein. PMID- 8220436 TI - Differences in induction by xenobiotics in murine tissues and the Hepa1c1c7 cell line of mRNAs encoding glutathione transferase, quinone reductase, and CYP1A P450s. AB - Levels of mRNAs encoding class-alpha glutathione transferases, class-mu glutathione transferases, quinone reductase, and cytochrome P450 1A were measured after xenobiotic induction in murine tissues and in the Hepa1c1c7 murine hepatoma cell line. RNA levels in liver and intestinal mucosa were determined after induction with phenobarbital, butylated hydroxyanisole, beta-naphthoflavone, isosafrole, or combinations of these compounds. The tissue culture cells were presented with combinations of butylated hydroxyanisole, tert-butyl-hydroquinone, and beta-naphthoflavone. In murine liver and intestinal mucosa, the greatest induction (5-15-fold) of glutathione transferases and quinone reductase was seen with butylated hydroxyanisole. Administration of phenobarbital or beta naphthoflavone has only a modest effect (2-3-fold). In contrast, cytochrome P450 1A mRNA levels increase only slightly after BHA induction but are induced dramatically by beta-naphthoflavone. The pattern of induction is different in Hepa1c1c7 cells; there the greatest induction of all mRNAs occurred with beta naphthoflavone. Administration of antioxidants with other xenobiotics increases mRNA levels only slightly over the levels obtained with BHA in murine tissues, or with beta-naphthoflavone in Hepa1c1c7 cells. mGSTM1 (GT8.7, Yb1), the most abundant glutathione transferase mRNA in murine liver, is also the most abundant glutathione transferase mRNA in both normal and induced Hepa1c1c7 cells. Our results suggest that BHA induction in murine liver and intestinal mucosa of class mu and class-alpha glutathione transferases may involve regulatory elements and mediators that function poorly in Hepa1c1c7 cells. PMID- 8220437 TI - Pharmacogenetics of cocaine: I. Locomotor activity and self-selection. AB - We investigated the effects of cocaine on multiple activity measures and cocaine self-selection in C57BL/6Ibg and DBA/2Ibg mice. Male mice were tested in an automated activity monitor at three doses of cocaine, 5, 15 and 30 mg kg-1. Activity measures included locomotion, rearings, stereotyped movements and wall seeking. Testing was conducted on 2 days with saline injection, i.p. on day one and cocaine i.p. injected on day two. We also tested other mice of both strains for cocaine ingestion in a two-choice test, pairing tap water with 40 mg% cocaine HCl in tap water. Two separate groups of mice received 15 or 30 mg kg-1 of cocaine i.p., killed at 5 min and brain cocaine levels were determined by HPLC. Cocaine produced dose-related increases in locomotion in both strains, with a delay in initial activation noticed at 30 mg kg-1 in C57s but not in DBAs. In DBAs, cocaine suppressed rearings and increased stereotyped movements while having no consistent effect on either behaviour in C57s. At all doses, cocaine produced moderate increases in proximity to the wall in DBAs and 30 mg kg-1 produced pronounced wall-seeking in C57s. At 15 and 30 mg kg-1 DBAs tended to have higher levels of cocaine in whole brain than did C57s. Finally, C57s consumed significantly more cocaine than did the DBAs. PMID- 8220438 TI - Pharmacogenetics of cocaine: II. Mesocorticolimbic and striatal dopamine and cocaine receptors in C57BL and DBA mice. AB - Studies were conducted to determine whether genetic differences in behavioural effects of cocaine in C57BL/6 and DBA/2 mice might be mediated by strain differences in dopamine and serotonin transporters and dopamine D1 and D2 receptors in specific brain regions. Binding characteristics of [3H]CFT, a cocaine analogue, in the presence of either GBR12909, a dopamine uptake blocker or fluoxetine, a serotonin uptake blocker and binding of [3H]-paroxetine, a specific serotonin uptake receptor antagonist, were evaluated. We observed regional differences in [3H]CFT binding parameters in the presence of GBR12909 or fluoxetine, but no strain differences by brain region were observed. There were no differences in [3H]paroxetine binding characteristics between corresponding brain regions from C57BL and DBA/2 mice. The D1 antagonist, [3H]SCH23390 and the D2 ligands [3H]sulpiride or [125I]epidepride were used to determine dopamine receptor characteristics. Regional differences were found in [3H]SCH23390 and [3H]sulpiride, with higher affinities and lower densities in frontal cortex compared to striatum; with no differences in [3H]SCH23390 binding in corresponding tissues from C57BL and DBA/2 brains. There were strain-related differences in [3H]sulpiride and in [3H]epidepride binding in striatal membranes with higher densities in C57BL than in DBA/2. Our findings suggest striatal D2 receptor differences are possibly involved in genetic differences in cocaine related behaviours. PMID- 8220439 TI - CYP2D6- and CYP3A-dependent metabolism of dextromethorphan in humans. AB - The metabolism of dextromethorphan, a drug used to probe genetically determined CYP2D6 activity has been investigated in vivo and in vitro. In vitro, kinetic parameters were determined in adult microsomes: Km for the O-demethylation was much lower than for N-demethylation (7 versus 650 microM) but Vmax was comparable. Fetal liver microsomes actively catalysed the N-demethylation of dextromethorphan, with kinetic parameters (Vmax and Km) quite similar in fetal and adult microsomal preparations while the O-demethylation did not exceed 5% of adult activity. In microsomes, the N-demethylation was inhibited by antibodies raised against CYP3A subfamily members although fetal microsomes were much less sensitive to immunoinhibition than adult microsomes. In vivo, urinary excretion of dextromethorphan and its three demethylated metabolites was examined in 155 adult volunteers and compared between extensive (n = 144, 92.9%) and poor (n = 11, 7.1%) metabolizers. The O-demethylation to dextrorphan is the rate-limiting step of metabolism. In 2D6 poor metabolizers, the N-demethylation to 3 methoxymorphinan is slightly higher than in 2D6 extensive metabolizers but does not compensate defective O-demethylation. The frequency distribution histograms of dextromethorphan/dextrorphan and 3-methoxymorphinan/3-hydroxymorphinan metabolic ratios appeared bimodally distributed, reflecting the participation of CYP2D6 in the O-demethylation reaction. They clearly differed from the random distribution of dextromethorphan/3-methoxymorphinan, and dextrorphan/3 hydroxymorphinan ratios among the population. These data clearly suggest that the N-demethylation of dextromethorphan is dependent on CYP3A and that both CYP2D6 and CYP3A are involved in the overall metabolism of dextromethorphan. PMID- 8220440 TI - Debrisoquine and metoprolol oxidation in Zambians: a population study. AB - The 0-8 h urinary distributions of the metabolic ratios of debrisoquine (10 mg) and metoprolol (100 mg) were measured in 102 healthy, unrelated, black Zambian medical students. There was a statistically significant correlation (rs = 0.60, p < 0.001; n = 88) between the debrisoquine/4-hydroxydebrisoquine (D/HD) and metoprolol/alpha-hydroxymetoprolol (M/HM) ratios. Bimodality in the distribution of the log10D/HD ratio was not evident from visual inspection and following kernel density analysis of the data, although two subjects (ratios 20, 22) would be classified as phenotypic poor metabolizers (PMs) based on the antimode used for Caucasian populations. The distribution of the log10M/HM ratio was skewed and on the basis of kernel density analysis, bimodal. It was clear from visual inspection of the data that the very high M/HM value (> or = 302) of one individual had a profound influence on the population M/HM ratio distribution. No HM was detected in the urine of this subject but he was not one of the two PMs of debrisoquine (D/HD ratio 1.54). H117/04, the major metabolite of metoprolol was also not detected in this sample. Since H117/04 was shown to be present in all samples from previous population studies, the possibility that this subject did not comply with the protocol could not be excluded. All other subjects had M/HM ratios < or = 12.5. These findings suggest that there is a dissociation in the control of debrisoquine and metoprolol oxidation in Zambians as has been observed previously in Nigerians. Furthermore, clear evidence that the metabolism of these drugs exhibits genetic polymorphism in Zambians was not obtained. PMID- 8220441 TI - Individual variability in p-aminobenzoic acid N-acetylation by human N acetyltransferase (NAT1) of peripheral blood. PMID- 8220442 TI - Isolation of an asparagus intracellular PR gene (AoPR1) wound-responsive promoter by the inverse polymerase chain reaction and its characterization in transgenic tobacco. AB - The Asparagus officinalis intracellular PR1 (AoPR1) gene is expressed in response to wounding and pathogen attack. We utilized the inverse polymerase chain reaction (IPCR) to isolate the cis-acting regulatory sequences of the AoPR1 gene following unsuccessful attempts to identify hybridizing clones in genomic libraries. Sequence analysis of two IPCR products revealed that a 347 bp intron was present in the AoPR1 gene and that it was probable that the AoPR1 regulatory sequence had been amplified. To test the AoPR1 cis-acting sequences for biological function a translational fusion was constructed with the beta glucuronidase (GUS) reporter gene and tested in tobacco. These data demonstrated that sequences 982 bp from the probable start of transcription are sufficient to direct wound-inducible transcription and that there is no signal peptide encoded by the first 31 residues of the predicted AoPR1 protein. Histochemical localization of GUS activity in transgenic tobacco demonstrated strong activity localized to wound and pathogen invasion sites. GUS activity was also found in mature pollen grains. PMID- 8220443 TI - Light-regulated and endogenous fluctuations of chloroplast transcript levels in Chlamydomonas. Regulation by transcription and RNA degradation. AB - Changes in the relative sizes of pools of transcripts of organelle genes during plastid development are common in flowering plants, but technical difficulties have prevented direct determinations of the effects of changes in rates of transcription and degradation on such fluctuations. It has been possible to follow both rates in Chlamydomonas reinhardtii. In synchronous or asynchronous cultures of cells grown in 12 h light/12 h dark periods, sizes of pools of transcripts of the chloroplast genes atpA, atpB, tufA, and psaB fluctuate. Differences in chloroplast transcript abundances in light/dark cycles were found to be cell cycle-independent but controlled by either an endogenous rhythm (atpA, atpB, and tufA) or by light (psaB). In vivo labeling experiments showed that transcriptional regulation and light/dark-regulated degradation both contribute, in gene-specific manners, to the level of transcripts of individual C. reinhardtii chloroplast genes in cells grown in alternating light/dark cycles. PMID- 8220444 TI - A wheat histone H3 promoter confers cell division-dependent and -independent expression of the gus A gene in transgenic rice plants. AB - To investigate developmental regulation of wheat histone H3 gene expression, the H3 promoter, which has its upstream sequence to -1711 (relative to the cap site as +1), was fused to the coding region of the gus A gene (-1711H3/GUS) and introduced into a monocot plant, rice. Detailed histochemical analysis revealed two distinct types of GUS expression in transgenic rice plants; one is cell division-dependent found in the apical meristem of shoots and roots and in young leaves, and another is cell division-independent detected in flower tissues including the anther wall and the pistil. In this study, replication-dependent expression occurring in non-dividing cells which undergo endoreduplication could not be discriminated from strict replication-independent expression. The observed expression pattern in different parts of roots suggested that the level of the H3/GUS gene expression is well correlated with activity of cell division in roots. To identify 5' sequences of the H3 promoter necessary for an accurate regulation of the GUS expression, two constructs containing truncated promoters, 908H3/GUS and -185H3/GUS, were analyzed in transiently expressed protoplasts, stably transformed calli and transgenic plants. The results indicated that the region from -909 to -1711 contains the positive cis-acting element(s) and that the proximal promoter region (up to -185) containing the conserved hexamer, octamer and nonamer motifs is sufficient to direct both cell division-dependent and -independent expression. The use of the meristem of roots regenerated from transformed calli for the analysis of cell division-dependent expression of plant genes is discussed. PMID- 8220445 TI - A versatile system for detecting transposition in Arabidopsis. AB - The maize transposable element Activator (Ac) has been shown to be active in a number of dicots, including Arabidopsis thaliana, whose small genome and short generation time have favored its wide adoption as a model organism for molecular genetic approaches to plant physiology and development. Using the Ac element and several bacterial and plant marker genes, we have devised a versatile system for identifying plants in which a transposon has excised and reinserted elsewhere in the genome. The transposons have been designed to facilitate the identification of insertions downstream of promoters and in the vicinity of enhancers by the inclusion of a beta-glucuronidase (GUS) gene either lacking a promoter or having a minimal promoter sequence. The system permits the transposon and the source of transposase to be maintained either stably in separate plants or in the same plant. Plants in which transposition is occurring can be identified by the frequent somatic activation of the GUS gene. The herbicide chlorsulfuron is used as a selective agent to identify progeny plants in which the transposon has excised from its original insertion site within a chlorsulfuron-resistant acetolactate synthase gene. Additional selectable markers permit the identification of plants containing a transposed element, but lacking transposase. Here we describe our initial characterization of the system and demonstrate its reliability and efficiency in identifying plants with transposed elements. PMID- 8220446 TI - Regulation of nitrate and nitrite reductase expression in Nicotiana plumbaginifolia leaves by nitrogen and carbon metabolites. AB - Nitrate (NR) and nitrite reductase (NiR) catalyse the reduction of nitrate to ammonium. The regulation of NR and NiR gene expression by carbohydrates (C) and nitrogen (N) metabolites was studied using detached leaves. In the dark, glucose fructose and sucrose supplied to detached green leaves of dark-adapted Nicotiana plumbaginifolia plants resulted in NR mRNA and protein accumulation and the loss of circadian rhythmicity in the size of the transcript pool. The characterization of transgenic plants expressing either a NR cDNA controlled by the 35S CaMV promoter or a transcriptional fusion between the tobacco nia1 (NR structural gene) promoter and the beta-glucuronidase reporter gene, led us to conclude that C metabolite control is taking place at the transcriptional level. Under low light conditions (limiting photosynthetic conditions), the supply of glutamine or glutamate resulted in a drop in the level of NR mRNA. Exogenously supplied carbohydrates partially antagonized this inhibitory effect suggesting that the availability of N and C metabolites affects the expression of the NR gene. The effects of carbohydrates and glutamine on NiR expression were also studied. NiR mRNA levels in the dark were relatively insensitive to feeding with glucose. Glutamate and glutamine were less efficient at decreasing NiR mRNA than NR mRNA levels. In contrast to NR, NiR mRNA levels were significantly increased by light treatments, indicating that NiR display regulatory characteristics reminiscent of photosynthetic genes such as the small subunit of ribulose bisphosphate carboxylase than to NR. PMID- 8220447 TI - Molecular homology among members of the R gene family in maize. AB - The R gene family determines the timing, distribution and amount of anthocyanin pigmentation in maize. This family comprises a set of regulatory genes, consisting of a cluster of several elements at the R locus, on chromosome 10, the Lc and Sn gene lying about two units R distal and B on chromosome 2. Each gene determines a tissue-specific pigmentation of different parts of the seed and plant. The proposed duplicated function of R, Sn, Lc and B loci is reflected in cDNA sequence similarity. In this paper an extensive analysis of the predicted proteins of the R, Sn, Lc and B genes together with a search for putative sites of post-translational modification is reported. A comparison with the prosite database discloses several N-glycosylation and phosphorylation sites, as well as the basic Helix-Loop-Helix (HLH) domain of transcriptional activators. Sn, Lc, and R-S show a high conservation of these sites, while B is more divergent. Analysis of the 5' leader of mRNA sequences discloses the presence of five ATG triplets with two upstream open reading frames (uORFs) of 38 and 15 amino acids and a loop structure indicating a possible mechanism of control at the translational level. It is conceivable that possible mechanisms acting at the translational and post-translational level could modulate the expression and the activation of these transcription factors. Northern analysis of various tissues of different R alleles highlights a strict correlation between pigment accumulation in different tissues and the expression of the regulatory and structural genes suggesting that the pattern of pigmentation relies on a mechanism of differential expression of the members of the R family. Analysis of the Sn promoter discloses the presence of several sequences resembling binding sites of known transcription factors (as GAGA and GT) that might be responsible for the spatial and light-induced expression of this gene. Two regions include a short sequence homologous to the consensus binding site of the B-HLH domain suggesting a self-regulatory control of the Sn gene. PMID- 8220448 TI - A repeating 11-mer amino acid motif and plant desiccation. AB - Among the proteins that accumulate as plant seeds desiccate are several protein families that are composed principally of a tandemly repeated 11-mer amino acid motif. Proteins containing the same motif accumulate in the desiccating leaves of a desiccation-tolerant plant species. This motif is characterized by apolar residues in positions 1, 2, 5 and 9, and charged or amide residues in positions 3, 6, 7, 8 and 11. An alpha helical arrangement of the 11-mer repeating unit gives an amphiphilic helix whose hydrophobic stripe twists in a right-handed fashion around the helix. Should these proteins dimerize via binding of their hydrophobic faces, a right-handed coiled coil would be formed. Such a structure has not previously been observed. A conceivable function for these proteins in ion sequestration in the desiccated state is proposed. PMID- 8220449 TI - Expression of maize Adh1 intron mutants in tobacco nuclei. AB - In vivo and in vitro gene transfer experiments have suggested that the elements mediating intron recognition differ in mammalian, yeast and plant nuclei. Differences in the sequence dependencies, which also exist between dicotyledonous and monocotyledonous nuclei, have prevented some monocot introns from being spliced in dicot nuclei. To locate elements which modulate efficient recognition of introns in dicot nuclei, the maize Adh1 gene has been expressed in full-length and single intron constructs in Nicotiana benthamiana nuclei using an autonomously replicating plant expression vector. Quantitative PCR-Southern analyses indicate that the inefficient splicing of the maize Adh1 intron 1 (57% AU) in these dicot nuclei can be dramatically enhanced by increasing the degree of U1 snRNA complementarity at the 5' splice site. This indicates that the 5' splice site plays a significant role in defining the splicing efficiency of an intron in dicot nuclei and that, most importantly, the remainder of this monocot intron contains no elements which inhibit its accurate recognition in dicot nuclei. Deletions in intron 3 (66% AU) which effectively move the 3' boundary between AU-rich intron and GC-rich exon sequences strongly activate a cryptic upstream splice site; those which do not reposition this boundary activate a downstream cryptic splice site. This suggests that 3' splice site selection in dicot nuclei is extremely flexible and not dependent on strict sequence requirements but rather on the transition points between introns and exons. Our results are consistent with a model in which potential splice sites are selected if they are located upstream (5' splice site) or downstream (3' splice site) of AU transition points and not if they are embedded within AU-rich sequences. PMID- 8220450 TI - Purification, characterization, and cell wall localization of an alpha-fucosidase that inactivates a xyloglucan oligosaccharin. AB - An alpha-fucosidase that releases fucosyl residues from oligosaccharide fragments of xyloglucan, a plant cell wall hemicellulosic polysaccharide, was purified to homogeneity from pea (Pisum sativum) epicotyls using a combination of cation exchange chromatography and isoelectric focusing. The alpha-fucosidase has a molecular mass of 20 kDa according to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The alpha-fucosidase has an isoelectric point of 5.5. The substrate specificity of the alpha-fucosidase was determined by high performance anion exchange chromatographic analysis of oligosaccharide substrates and products. The enzyme hydrolyzes the terminal alpha-1,2-fucosidic linkage of oligosaccharides and does not cleave p-nitrophenyl-alpha-L-fucoside. The enzyme does not release measurable amounts of fucosyl residues from large polysaccharides. The subcellular localization of alpha-fucosidase in pea stems and leaves has been studied by immunogold cytochemistry. The alpha-fucosidase accumulates in primary cell walls and is not detectable in the middle lamella or in the cytoplasm of 8-day-old stem tissue and 14-day-old leaf tissue. alpha Fucosidase activity was readily detected in extracts of 8-day-old stem tissue. No significant alpha-fucosidase activity or immunogold labeling of the alpha fucosidase was detected in 2- and 4-day-old stem tissue indicating that production of alpha-fucosidase is developmentally regulated. PMID- 8220451 TI - A non-specific lipid transfer protein from Arabidopsis is a cell wall protein. AB - Lipid transfer proteins (LTPs), mediate the transfer of phospholipids between membranes in vitro. However, the in vivo function of LTPs is not known. To determine the precise location of a non-specific LTP from Arabidopsis, a cDNA clone was used to produce an Arabidopsis LTP:protein A fusion. Antibodies raised against the fusion were used to localize the Arabidopsis LTP by immunoelectron microscopy. LTP was found to be located in the cell wall, mainly in epidermal cells. This location appears to be inconsistent with the proposed role of the protein in intracellular lipid transfer. PMID- 8220452 TI - The pea plastocyanin promoter directs cell-specific but not full light-regulated expression in transgenic tobacco plants. AB - A series of 5' deletions of the pea plastocyanin gene (petE) promoter fused to the beta-glucuronidase (GUS) reporter gene has been examined for expression in transgenic tobacco plants. Strong positive and negative cis-elements which modulate quantitative expression of the transgene in the light and the dark have been detected within the petE promoter. Disruption of a negative regulatory element at -784 bp produced the strongest photosynthesis-gene promoter so far described. Histochemical analysis demonstrated that all petE-GUS constructs directed expression in chloroplast-containing cells, and that a region from -176 bp to +4 bp from the translation start site was sufficient for such cell-specific expression. The petE-promoter fusions were expressed at high levels in etiolated transgenic tobacco seedlings but there was no marked induction of GUS activity in the light. The endogenous tobacco plastocyanin genes and the complete pea plastocyanin gene in transgenic tobacco plants were also expressed in the dark, but showed a three- to sevenfold increase in the light. This indicates a requirement for sequences 3' to the promoter for the full light response of the petE gene. PMID- 8220453 TI - Receptor-like protein kinase genes of Arabidopsis thaliana. AB - The isolation of a maize cDNA clone that encodes a membrane spanning protein kinase related to the self-incompatibility glycoproteins (SLG) of Brassica and structurally similar to the growth factor receptor tyrosine kinases has recently been reported. Three distinct receptor-like protein kinase (RLK) cDNA clones from Arabidopsis thaliana have now been identified. Two of the Arabidopsis RLK genes encode SLG-related protein kinases but have different patterns of expression: one is expressed predominantly in rosettes while the other is expressed primarily in roots. The third RLK gene contains an extracellular domain that consists of 21 leucine-rich repeats that are analogous to the leucine-rich repeats found in proteins from humans, flies and yeast. The Arabidopsis leucine-rich gene is expressed at equivalent levels in roots and rosettes. These results show that there are several genes in higher plants that encode members of the receptor protein kinase superfamily. The structural diversity and differential expression of these genes suggest that each plays a distinct and possibly important role in cellular signaling in plants. PMID- 8220454 TI - Expression of the alpha-thionin gene from barley in tobacco confers enhanced resistance to bacterial pathogens. AB - Thionins are cysteine-rich, 5 kDa polypeptides which are toxic to plant pathogens in vitro. Expression of the gene encoding alpha-thionin from barley endosperm, under the 35S promoter from cauliflower mosaic virus, conferred to transgenic tobacco enhanced resistance to the bacterial plant pathogens Pseudomonas syringae pv. tabaci 153 and P. syringae pv. syringae. The barley alpha-thionin gene, which has two introns, was correctly spliced in tobacco. The alpha-thionin in transgenic plants had the expected mobility in the gradient, when separated by high-performance liquid chromatography, reacted with monospecific antibodies and showed the expected antibiotic properties in vitro. PMID- 8220455 TI - Conserved regulation of the soybean early nodulin ENOD2 gene promoter in determine and indeterminate transgenic root nodules. AB - The beta-glucuronidase (GUS) activity expressed from the soybean early nodulin ENOD2(B) gene promoter was localized histochemically in nodules of Lotus corniculatus and Trifolium repens. In both the determinate Lotus nodules and the indeterminate Trifolium nodules, activity was found in the parenchyma cells and especially in cells close to the vascular tissue of nodules. The characteristic cell-specific expression of the soybean ENOD2 gene was therefore maintained by the ENOD2(B) promoter in the two developmentally different nodule types. Important DNA elements recognized in transgenic nodules were identified by deletion and hybrid promoter analysis in Lotus corniculatus. An indispensable positive element (PE) and a possible tissue specific element was defined between positions -1792 and -1582 from the transcription start site. Another qualitative control element located between -380 and -53 conferred the ENOD2 characteristic cell type expression on hybrid promoters. This element contains the conserved nodulin gene sequences CTCTT and AAAGAT. In contrast to the ENOD2(B) promoter a chimeric leghemoglobin Ibc3-GUS gene was expressed in the infected cells of both types of nodules. In the indeterminate nodules expression was restricted to the interzone II-III and the active nitrogen-fixing zone III. Interchange of the distal strong positive element (SPE) of Ibc3 and the ENOD2 positive element resulted in an expression pattern different from that observed for the Ibc3 and ENOD2 genes, indicating that different interactions of trans-acting factors are required for regulation of early as well as late nodulin genes. PMID- 8220456 TI - Alkali treatment for rapid preparation of plant material for reliable PCR analysis. AB - For plant genetics, it would be useful to monitor easily the segregation of different alleles using the polymerase chain reaction (PCR). Preparation of DNA templates from individual plants needs to be rapid and reliable. A one tube protocol is described that involves subjecting plant tissue pieces to alkali, neutralization and heat denaturation prior to PCR analysis, and that proved to be much faster and more reliable than published protocols. PMID- 8220457 TI - Inflorescence-specific genes from Arabidopsis thaliana encoding glycine-rich proteins. AB - Genomic and cDNA clones for three inflorescence-specific genes from Arabidopsis thaliana were isolated and characterized. The genes are tandemly organized in the genome on a 10 kb fragment. The expression of these genes is coordinately regulated in a developmental and organ-specific pattern. They are expressed predominantly in anthers at the later stage of flower development. The primary structure of the encoded gene products exhibits comparable features consisting of a hydrophobic domain at the N-terminal region followed by repeated glycine-rich motifs. Little homology is observed either between the glycine-rich domain of the three genes or with previously described glycine-rich proteins from other plant species. PMID- 8220458 TI - Analysis of three tissue-specific elements from the wheat Cab-1 enhancer. AB - The genes encoding the major light-harvesting antenna chlorophyll a/b-binding protein (Cab) of higher plants are regulated by light at the transcriptional level. In addition, their expression is largely restricted to photosynthetically competent organs such as leaves. A 268 bp fragment of the Cab-1 promoter from wheat functions as a light-responsive and organ-specific enhancer in transgenic tobacco. Using DNase I footprinting, four different regions have been mapped (Cab1-A, Cab1-B, Cab1-C and Cab1-D) in this fragment that bind to protein factors in tobacco nuclear extracts. Three of these regions (A, B and C) coincide with sequences that have been found to be functionally important from previous cis element analyses. Synthetic tetramers of these three sites interact with different proteins in gel retardation assays. In addition, cross-competition analyses demonstrate that Cab1-C is likely to interact with ASF-2, a tobacco DNA binding activity that binds to a conserved GATA element found in many dicot Cab promoters. In transgenic tobacco, a 95 bp fragment of the Cab-1 enhancer containing the A, B and C regions can confer leaf expression when fused upstream of a truncated derivative of the cauliflower mosaic virus (CaMV) 35S promoter. However, expression observed with this enhancer fragment in the promoter context of these studies does not appear to be significantly dependent on light. Similar results were obtained with synthetic tetramers of Cab1-A, -B or -C. These data thus suggest that the wheat Cab-1 enhancer contains at least three distinct elements that contribute to leaf-specific expression in transgenic tobacco. Interaction between factors binding to these positive elements and those that bind elsewhere in the Cab-1 enhancer may be necessary for light-responsive transcriptional activation. PMID- 8220459 TI - Characterization of the catalase antioxidant defense gene Cat1 of maize, and its developmentally regulated expression in transgenic tobacco. AB - A genomic clone containing the maize Cat1 gene has been isolated and its complete DNA sequence determined. The start of transcription has been mapped by primer extension. Six introns were identified in the Cat1 coding region. In order to determine the tissue-specific expression pattern of the Cat1 gene, promoter reporter gene fusion constructs were made consisting of 2.5 kb and 0.8 kb of the 5' Cat1 sequence fused to the coding region of the beta-glucuronidase (GUS) gene. These fusion constructs were introduced into Nicotiana tabacum cv. Burley 21 and the expression of Cat1-GUS in various tissues was examined. In transgenic tobacco, the Cat1 promoter can drive GUS expression at relatively high levels in mature seeds. GUS activity starts to accumulate at about 10 days after flowering, reaching a maximum at about 22 days after flowering, and decreases thereafter, but persists until after seed desiccation through early germination. Low levels of GUS activity can be detected in pollen. This corresponds to the Cat1 expression pattern observed in maize. PMID- 8220460 TI - The 54 kDa RNA-binding protein from mustard chloroplasts mediates endonucleolytic transcript 3' end formation in vitro. AB - A 54 kDa protein from mustard chloroplasts was previously shown to interact specifically with a conserved U-rich sequence element in RNA derived from the 3' flanking regions of the plastid trnK and rps16 genes, which code for tRNA(Lys) and ribosomal protein CS19, respectively (Nickelsen and Link, 1991). This RNA binding protein has now been purified by affinity chromatography on heparin Sepharose and poly(U) Sepharose. In vitro processing experiments and nuclease S1 analyses of the processing products revealed that the 54 kDa polypeptide is an endonuclease. The in vitro cleavage sites are consistent with the positions of corresponding transcript in vivo 3' ends downstream of trnK and rps16, suggesting that RNA 3' end formation takes place endonucleolytically also in vivo. PMID- 8220461 TI - Homologs of the essential ubiquitin conjugating enzymes UBC1, 4, and 5 in yeast are encoded by a multigene family in Arabidopsis thaliana. AB - The covalent attachment of the 76 amino acid protein ubiquitin is an important prerequisite for the degradation of many eukaryotic proteins. The specificity of this ligation is accomplished in part by a family of distinct ubiquitin conjugating enzymes (E2s) working in concert with specific ubiquitin-protein ligases (E3s). Three essential E2s in yeast encoded by ScUBC1, -4, and -5 comprise a functionally overlapping E2 subfamily that appears responsible for degrading most abnormal and short-lived proteins. A 15 kDa E2 protein homologous to this family has been identified previously in wheat germ, designated TaE2(15kDa) (Girod and Vierstra (1993) J. Biol. Chem. 268, 955-960). This E2 is responsible for much of the ubiquitin conjugating activity observed in wheat germ extracts and works together with a unique E3 (designated E3 gamma) for substrate recognition. In this paper, the cloning of five genes encoding E2(15kDa) from Arabidiopsis thaliana is described (designated AtUBC8-12). They encode 149 amino acid basic proteins 94-98% similar to each other and 88-92% similar to ScUBC4 at the amino acid sequence level. In contrast, AtUBC8-12 are only 55-65% similar to the Arabidopsis E2s encoded by AtUBC1, -4, and -7. The AtUBC8-12 proteins do not contain N- or C-terminal extensions and have the active site at residue Cys-86, based on their homology with other E2s. Analyses of genomic Southern blots are consistent with the existence of multiple members encoding this E2 subfamily. AtUBC8-12 are transcribed to yield about 800 nucleotide mRNAs that, unlike ScUBC4 and -5, are not strongly induced by heat shock.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8220462 TI - Petunia hybrida genes related to the maize regulatory C1 gene and to animal myb proto-oncogenes. AB - The maize C1 gene is a regulatory gene of the anthocyanin pathway. It is a part of a multigene family whose predicted protein products contain a region with homology to the DNA-binding domain of myb proto-oncogene products. Using as a probe an oligonucleotide mixture encoding a highly conserved region in plant MYB proteins, cDNAs encoding three related polypeptides expressed in the flower of Petunia hybrida have been isolated. Predicted proteins are 280-517 amino acids long and show sequence similarities among themselves as well as with other MYB proteins (45-80% amino acid identity) in the MYB DNA-binding domain. Outside this domain no significant sequence similarity was found. However, in all cases regions with structural characteristics of activator domains were found. Analysis with Southern blots allowed an estimation of at least 20-30 myb genes in P. hybrida. Expression patterns were specific for each gene as shown by Northern blotting analysis. Subcellular location studies of the largest MYB product, by both immunoblotting of the protein in subcellular fractions and by 'in situ' immunolocation experiments, showed that it is a nuclear protein. The role of MYB proteins as transcriptional activators regulating the synthesis of different anthocyanin(flavonoid)-related compounds is discussed. PMID- 8220463 TI - Salicylic acid-inducible binding of a tobacco nuclear protein to a 10 bp sequence which is highly conserved amongst stress-inducible genes. AB - A 10 bp sequence motif (TCATCTTCTT) which is repeated several times in the 5' non transcribed region of a barley beta-1,3-glucanase gene is also present in the non translated regions of over 30 different plant genes which are known to be induced by one or more forms of stress. Gel retardation assays and South-western blotting experiments provide evidence that the motif is the binding site for a tobacco nuclear protein with an apparent molecular weight of 40 kDa. Binding activity is increased when nuclear extracts from salicylic acid-treated plants are analysed compared with extracts from control plants, indicating that the protein itself is either induced or modified under conditions of stress. These observations suggest roles for the 10 bp motif and its binding protein as cis- and trans-acting regulators of gene expression during response to stress. PMID- 8220464 TI - Characterization of GmENOD40, a gene showing novel patterns of cell-specific expression during soybean nodule development. AB - In this paper, the soybean 'early nodulin' clone pGmENOD40 is characterized. The GmENOD40 encoded protein does not contain methionine and does not show homology to proteins identified so far. In situ hybridizations showed that this gene has a complex expression pattern during development of determinate soybean nodules. At early stages of development transcription is induced in dividing root cortical cells, the nodule primordium and the pericycle of the root vascular bundle. In mature soybean nodules, the gene is expressed in the uninfected cells of the central tissue and in the pericycle of the nodule vascular bundles. Studies on nodules devoid of intracellular bacteria and infection threads, showed that the expression of the gene in the nodule primordium is induced in these empty nodules, while the induction of the GmENOD40 gene in the nodule vascular bundle requires the presence of intracellular bacteria or infection threads. A pea cDNA clone homologous to GmENOD40 was isolated to enable in situ hybridization studies on indeterminate nodules. The expression patterns in both determinate and indeterminate nodules suggests that the ENOD40 protein might have a transport function. PMID- 8220465 TI - Expression of antisense nodulin-35 RNA in Vigna aconitifolia transgenic root nodules retards peroxisome development and affects nitrogen availability to the plant. AB - A nodulin-35 (N-35) cDNA encoding nodule-specific uricase (EC 1.7.3.3.) was isolated from a Vigna aconitifolia (mothbean) root nodule cDNA library. Sequence analysis of Vigna uricase (VN-35) cDNA revealed 90% homology to that of soybean. The VN-35 cDNA was inserted in the antisense orientation downstream of the caMV 35S promoter, and transgenic hairy roots were formed on Vigna plants using Agrobacterium rhizogenes. Infection with Bradyrhizobium (cowpea) gave rise to root nodules on transgenic hairy roots supported by the wild-type shoot. Expression of antisense VN-35 RNA was detected in transgenic nodules on individual roots using polymerase chain reaction (PCR). The nodules expressing antisense VN-35 RNA were smaller in size and showed lower uricase activity than nodules formed on the hairy roots transformed with a binary vector containing beta-glucuronidase (GUS) gene (used as control), and the plants exhibited nitrogen deficiency symptoms. Ultrastructural analysis and immunogold labeling with antibody against soybean N-35 revealed that the growth of peroxisomes was retarded in transgenic nodules expressing antisense VN-35 RNA. These data suggest that a reduction in ureide biosynthesis limits the availability of symbiotically reduced nitrogen to the plant. The nodules of tropical legumes appear to be specialized in nitrogen assimilation and are developmentally controlled to produce and transport ureides. PMID- 8220466 TI - The plant homologue of MAP kinase is expressed in a cell cycle-dependent and organ-specific manner. AB - In animals, MAP kinase plays a key role in growth factor-stimulated signalling and in mitosis. The isolation of a Medicago sativa cDNA clone MsK7 which shows 52% identity to animal MAP kinases is reported. The deduced protein sequence shows all the important structural features of MAP kinases and also contains the highly conserved Thr-183 and Tyr-185 residues. Northern analysis of synchronized alfalfa cells showed that the MsK7 kinase gene is expressed at low levels in G1 phase but at higher levels in S and G2 phases of the cell cycle. In the plant, only stems and roots were found to contain MAP kinase MsK7 mRNA. Southern and PCR analyses indicated that alfalfa contains at least four highly related MAP kinase genes. PMID- 8220467 TI - Identification of cis elements involved in Commelina yellow mottle virus promoter activity. AB - Commelina yellow mottle virus (CoYMV) is a double-stranded DNA virus that infects a monocot host. A promoter fragment isolated from CoYMV is a strong promoter when assayed after transient introduction into monocot and dicot suspension cells and is highly active in vascular cells of flowers, leaves, stems and roots of stably transformed tobacco plants. Here it is reported that in stably transformed maize calli and transgenic tobacco leaves the CoYMV and CaMV 35S promoters exhibit similar amounts of activity. Deletion of the sequences located distal to nucleotide -230 relative to the start of transcription has no significant effect on promoter strength or tissue specificity. The region between -230 and -200 shares sequence similarity with the as-1 promoter element of the CaMV 35S promoter. Deletion of this as-1-like motif decreases promoter activity in maize suspension cells by 85%. Analysis of deletions affecting the -200 to -52 region indicates that sequences located between -159 and -84 are required for activity in vascular tissues. In addition, this region exhibits properties of a vascular tissue-specific enhancer since it confers vascular expression in an orientation independent manner when fused to promoters that are not normally active in vascular tissues. PMID- 8220468 TI - Temporal and spatial expression of a thiolprotease gene during pea ovary senescence, and its regulation by gibberellin. PMID- 8220469 TI - Effect of lateral suppressor on petal initiation in tomato. AB - Flowers developing on tomato (Lycopersicon esculentum) plants homozygous for the lateral suppressor (ls) mutation lack petals. Scanning electron micrographs revealed that in ls plants no second whorl organs were initiated. The initiation of first, third, and fourth whorl organs were unaffected by this mutation. To investigate interactions between the cells in different layers of the floral meristem during organ initiation, a periclinal chimera between wild-type and ls tomato was generated. Flowers of the chimera having ls cells in the outer meristem layer (L1) and wild-type cells in internal layers (L2 and L3) developed normally, including the initiation of organ primordia that differentiated as petals in normal positions within the second whorl. L1 of the chimera developed in a non-autonomous manner during petal development. Thus, wild-type cells occupying the internal meristem layers provided developmental cues necessary for initiation of petal primordia at appropriate positions on the floral meristem. L1 cells carrying the lateral suppressor mutation were fully capable of responding to this information and differentiated appropriately. PMID- 8220470 TI - BPF-1, a pathogen-induced DNA-binding protein involved in the plant defense response. AB - The mechanisms by which plants restrict the growth of pathogens include transient activation of numerous defense-related genes. Box P is a putative cis-acting element of a distinct group of such genes, including those encoding the enzyme phenylalanine ammonialyase (PAL). A DNA-binding activity to Box P was identified in nuclear extracts from cultured parsley cells and a cDNA encoding the protein BPF-1 (Box P-binding Factor) partially characterized. BPF-1 binds to this element with specificity similar to that of the binding activity in nuclear extracts. BPF 1 mRNA accumulates rapidly in elicitor-treated parsley cells and around fungal infection sites on parsley leaves. This accumulation is, at least partly, due to a rapid and transient increase in the transcription rate of BPF-1. Moreover, tight correlation between the relative amounts of BPF-1 and PAL mRNAs was observed in different organs of a parsley plant. These results are consistent with the hypothesis that BPF-1 is involved in disease resistance by modulating plant defense gene expression. PMID- 8220471 TI - Correlation between arrested secondary plasmodesmal development and onset of accelerated leaf senescence in yeast acid invertase transgenic tobacco plants. AB - Mature leaves of a transgenic tobacco plant (Nicotiana tabacum L. var. Samsun, line A41-10) that constitutively express a yeast-derived acid invertase gene develop symptoms which are characterized by the presence of greenish-yellow and green sectors in the same leaf, and onset of early leaf senescence. Previous studies indicated that invertase activity was two- to threefold higher in the greenish-yellow sectors than in the green sectors. Our structural analyses revealed that development of secondary plasmodesmata, via modification of existing primary plasmodesmata, between mesophyll cells was inhibited severely in the greenish-yellow sectors, but only marginally in the green sectors. In contrast, the structure and function of primary plasmodesmata in the same symptomatic sectors remained unaltered as determined by structural and dye coupling studies. It is hypothesized that secondary plasmodesmata differ from primary plasmodesmata in having special abilities to traffic information molecules to coordinate leaf development and physiological function(s). Arrest of secondary plasmodesmal development by high invertase activity in the transgenic tobacco leaf may have prevented this type of trafficking and hence resulted in early leaf senescence. The results also indicate that the yeast acid invertase expressing tobacco may provide an effective experimental system for the molecular characterization of cellular mechanisms that regulate the development, function, and possible turnover of secondary plasmodesmata. PMID- 8220472 TI - Soluble isoforms of starch synthase and starch-branching enzyme also occur within starch granules in developing pea embryos. AB - Developing wild-type pea embryos contain two major isoforms of starch synthase and two isoforms of starch-branching enzyme. One of the starch synthases and both starch-branching enzymes occur both in the soluble fraction and tightly bound to starch granules. The other starch synthase, which is very similar to the waxy proteins of other species, is exclusively granule-bound., It is inactive when solubilized in a native form from starch granules, but activity is recovered when the SDS-denatured protein is reconstituted from polyacrylamide gels. Evidence is presented which indicates that all of these proteins become incorporated within the structure of the granule as it grows. It is proposed that the granule-bound waxy protein is active in vivo at the granule surface, whereas the remaining proteins are active in the soluble fraction of the amyloplast. The proteins become trapped within the granule matrix as the polymers they synthesize crystallize around them, and they probably play no further part in polymer synthesis. PMID- 8220473 TI - Analysis of a desiccation and ABA-responsive promoter isolated from the resurrection plant Craterostigma plantagineum. AB - The resurrection plant Craterostigma plantagineum can recover from severe desiccation within 24 h of contact with water, and it is used as a model system to analyse desiccation tolerance in higher plants. During drying or ABA treatment a specific set of transcripts accumulates rapidly in leaves and other tissues. In order to study transcriptional mechanisms of stress-induced gene expression one gene (CDeT27-45) was selected for promoter analysis. Chimeric gene fusions were constructed of the CDeT27-45 promoter and beta-glucuronidase or luciferase. These constructs were tested in a homologous transient expression system which allowed the identification of promoter elements conferring ABA inducibility. By introducing the chimeric gene fusions into tobacco via Agrobacterium-mediated transformation we found that the promoter activity is under strict tissue specific and developmental control. In tobacco the promoter was only active in developing embryos and in mature pollen grains-two tissues which are naturally desiccation tolerant in tobacco. The specific temporal expression pattern was attributed to particular 5' upstream sequences. The promoter analysis presented here should allow the separation of important regulatory components as a first step in dissecting events in the signal transduction chain. PMID- 8220474 TI - Isolation and characterization of a cDNA clone from Catharanthus roseus encoding NADPH:cytochrome P-450 reductase, an enzyme essential for reactions catalysed by cytochrome P-450 mono-oxygenases in plants. AB - The membrane-bound flavoprotein NADPH:cytochrome P-450 (cytochrome c) reductase, that functions in electron transfer to cytochrome P-450 monooxygenases, was purified from a cell suspension culture of the higher plant Catharanthus roseus. Anti-serum raised against the purified protein was found to inhibit NADPH:cytochrome c reductase activity as well as the activities of the cytochrome P-450 enzymes geraniol 10-hydroxylase and trans-cinnamate 4-hydroxylase, which are involved in alkaloid biosynthesis and phenylpropanoid biosynthesis, respectively. Immunoscreening of a C. roseus cDNA expression library resulted in the isolation of a partial NADPH: cytochrome P-450 reductase cDNA clone, which was identified on the basis of sequence homology with NADPH:cytochrome P-450 reductases from yeast and animal species. The identify of the cDNA was confirmed by expression in Escherichia coli as a functional protein capable of NADPH dependent reduction of cytochrome c and neotetrazolium, two in vitro substrates for the reductase. The N-terminal sequence of the reductase, which was not present in the cDNA clone, was determined from a genomic NADPH: cytochrome P-450 reductase clone. It was demonstrated that the reductase probably is encoded by a single copy gene. A sequence comparison of this plant NADPH:cytochrome P-450 reductase with the corresponding enzymes from yeast and animals species showed that functional domains involved in binding of the cofactors FMN, FAD and NADPH are highly conserved between all kingdoms. In C. roseus cell cultures a rapid increase of the reductase steady state mRNA level was observed after the addition of fungal elicitor preparations that are known to induce cytochrome P-450 dependent biosynthetic pathways. PMID- 8220475 TI - cdc2MsB, a cognate cdc2 gene from alfalfa, complements the G1/S but not the G2/M transition of budding yeast cdc28 mutants. AB - The product of the cdc2 gene encodes the p34cdc2 protein kinase that controls entry of yeast cells into S phase and mitosis. In higher eukaryotes, at least two cdc2-like genes appear to be involved in these processes. A cdc2 homologous gene has previously been isolated from alfalfa and shown to complement a fission yeast cdc2ts mutant. Here the isolation of cdc2MsB, a cognate cdc2 gene from alfalfa (Medicago sativa) is reported. Southern blot analysis shows that cdc2MsA and cdc2MsB are present as single copy genes in different tetraploid Medicago species. cdc2MsB encodes a slightly larger mRNA (1.5 kb) than cdc2MsA (1.4 kb). Both genes were found to be expressed at similar steady state levels in different alfalfa organs. Expression levels of both cdc2Ms genes correlate with the proliferative state of the organs. Complementation studies revealed that in contrast to cdc2MsA, cdc2MsB was not able to rescue a cdc2ts fission yeast mutant. cdc2MsB was also unable to rescue a G2/M-arrested cdc28ts budding yeast mutant which could be rescued by expression of the cdc2MsA gene. Conversely, cdc2MsB but not cdc2MsA was found to complement the G1/S block of another cdc28ts budding yeast mutant. These results suggest that cdc2MsA and cdc2MsB function at different control points in the cell cycle. PMID- 8220476 TI - Specificity of a promoter from the rice tungro bacilliform virus for expression in phloem tissues. AB - The major promoter region for the transcription of the genome of rice tungro bacilliform virus (RTBV), a newly described badnavirus, has been identified. Fragments of the RTBV genome upstream of the site of transcription initiation were isolated and tested for promoter activity using a beta-glucuronidase receptor gene (gusA). Assays of transient gusA expression were performed following introduction of the chimeric gene into protoplasts via electroporation. The chimeric RTBV-promoter: gusA gene was more active in rice protoplasts than in maize or tobacco protoplasts, but was weaker than gusA controlled by an enhanced 35S promoter from cauliflower mosaic virus. Analysis of gusA gene expression following introduction of chimeric reporter genes into intact leaves via micro projectile bombardment indicated that the GUS activity is present primarily in vascular tissues. Transgenic rice plants carrying the chimeric gusA gene had GUS activity only in the phloem of the vascular bundles in the leaf. Tissue printing studies demonstrated that RTBV accumulates in the vascular bundles of infected rice leaves. The results of our study indicate that phloem-specific expression from the RTBV promoter is an intrinsic property of the viral promoter. PMID- 8220477 TI - A protein phosphatase 1 from Arabidopsis thaliana restores temperature sensitivity of a Schizosaccharomyces pombe cdc25ts/wee1- double mutant. AB - There is increasing evidence that the mechanisms controlling the eukaryotic cell cycle are regulated by protein phosphorylation/dephosphorylation cascades. The catalytic subunit of the protein phosphatase 1 is implicated genetically and biochemically in the complex network that regulates mitosis. To investigate further the cell division in plants, we have isolated and characterized two full length cDNAs from Arabidopsis thaliana, PP1A-At1 and PP1A-At2, encoding polypeptides highly homologous to known protein phosphatase 1 (PP1). DNA gel blot analysis suggests that the protein phosphatases 1 might form a small gene family in Arabidopsis. Northern analysis shows that transcripts are present in all plant organs. In cell cultures, the PP1 mRNA levels are differentially affected by treatment with drugs that block cell division. The expression of PP1A-At1 in a Schizosaccharomyces pombe cdc25ts/wee1- double-mutant strain restores temperature sensitivity, showing that the Arabidopsis phosphatase gene is capable of interacting with genes that regulate the fission yeast mitotic apparatus. However, the dis2-11 S. pombe strain, which has a cold-sensitive allele of the phosphatase 1 gene, is not rescued by expression of the PP1A-At1 gene, suggesting that the plant cDNA is not a functional homolog of the fission yeast gene. PMID- 8220478 TI - Differences in DNA-methylation are associated with a paramutation phenomenon in transgenic petunia. AB - The transgenic petunia line 17-R contains one copy of the maize A1 gene which mediates brick-red pelargonidin pigmentation of the flower. A white derivative, 17-W, was isolated from homozygous progeny of this line in which no pelargonidin pigmentation was observed. In 17-W the 35S promoter driving the A1 gene was hypermethylated, in contrast to its hypomethylated state in 17-R. Progeny plants carrying both the 17-R and 17-W allele did not show the expected A1 phenotype. Predominantly white progeny and variable plants were observed which showed a continuous change in pattern and intensity of pelargonidin pigmentation. This reduction of A1 activity argues for a semidominant effect of the 17-W allele which inhibits the activity of its homologue, 17-R. This system shows striking similarities to some paramutation phenomena in plants which represent a heritable change in gene function of a paramutable allele directed by a paramutagenic homologue. The analysis of the methylation patterns of the A1 alleles suggests that interactions between differentially methylated alleles are responsible for the paramutation-like effect which is mediated by somatic pairing. The analogy of this system to other phenomena based on homology-dependent interlocus trans inactivation supports the assumption that those may be based on a related mechanism which includes an interaction between ectopic homologues. PMID- 8220479 TI - A 42 bp promoter fragment of the gene for subunit III of photosystem I (psaF) is crucial for its activity. AB - The promoter of the gene for the subunit III of photosystem I reaction center (psaF) from spinach has been dissected and studied via promoter/GUS gene fusions in transgenic tobacco. It possesses an architecture that differs from any other spinach promoter of genes encoding proteins involved in photosynthesis studied to date. A 42 bp region located between -220 and -179 bp upstream of the transcription start site has been identified that is indispensable for expression and binds a trans-acting factor. Maximal light-response is obtained with a -220/+ 163 bp segment, whereas longer promoter sequences are significantly less effective, indicating the existence of upstream elements with silencer characteristics. F1 seedlings show different spatial expression patterns in darkness or light. Etiolated seedlings display high GUS activity in the upper hypocotyl, the hook region and the vascular tissue of the cotyledons, whereas in light-grown seedlings no activity was detected in the hypocotyl and almost all cells of the cotyledons express the GUS gene. PMID- 8220480 TI - A basic-type PR-1 promoter directs ethylene responsiveness, vascular and abscission zone-specific expression. AB - Pathogenesis-related (PR) proteins form a heterogeneous group of host-encoded, low-molecular-mass proteins that are secreted through the exocytic pathway. They are synthesized by the plant in response to various stimuli, including pathogen attack or exposure to certain chemicals. The PRB-1b gene of Nicotiana tabacum codes for a basic-type PR-1 protein whose transcription is regulated by ethylene. A minimal ethylene-responsive promoter element was defined by deletion analysis in transgenic tobacco plants. Promoter sequences containing 213 bp or more were sufficient to enhance a 20-fold increase of beta-glucuronidase reporter gene expression in transgenic tobacco leaves exposed to 20 microliters l-1 of ethylene, while 67 bp were not sufficient to trigger ethylene responsiveness. All the constructs that retained ethylene inducibility exhibited phloem-specific activity, which was constitutive in petiole and pedicel abscission zones. This functional study was correlated to an in vitro screening of the major nuclear proteins' binding sites present on the promoter. Gel-shift analysis using nuclear extracts from ethylene-treated and non-treated plants revealed five sequence specific protein-DNA complexes on promoter sequences spanning -863 to -142 bp. Constitutive expression of the basic-type PR-1 genes at the leaf and petiole or flower and pedicel interfaces may represent pre-emption of plant defenses against potential pathogens, suggesting a functional similarity to pathogen-induced expression in the leaf. PMID- 8220481 TI - Combinatorial interactions between positive and negative cis-acting elements control spatial patterns of 4CL-1 expression in transgenic tobacco. AB - The phenylpropanoid enzyme 4-coumarate:coenzyme A ligase (4CL) plays a key role in linking general phenylpropanoid metabolism to end-product specific biosynthetic pathways. During vascular system and floral organ differentiation, the parsley 4CL-1 gene is expressed in a restricted set of tissues and cell types where 4CL activity is required to supply precursors for the synthesis of diverse phenylpropanoid-derived products such as lignin and flavonoids. In order to localize cis-acting elements which specify complex patterns of 4CL-1 expression, we analyzed the expression of internally deleted promoter fragment-GUS fusions in tobacco plants and parsley protoplasts. Elements located between -244 and -78 were required for most aspects of developmentally regulated expression. Within this region, three separate promotor domains containing partially redundant cis elements directed vascular-specific expression when combined with a TATA-proximal domain. A negative cis-acting element which represses phloem expression was revealed in one of the domains and appears to be responsible for restricting vascular expression to the xylem. Distinct but overlapping promoter domain combinations were required for expression in floral organs, suggesting that different combinations of cis-acting elements may direct expression in different organs. Gel retardation assays were used to demonstrate the formation of DNA protein complexes between factors present in nuclear extracts of parsley tissue culture cells and various tobacco organs and a 4CL-1 promoter fragment. Competition experiments showed that complex formation required the presence of a 42 bp promoter domain shown to be critical for 4CL-1 expression in vascular and floral tissues. The results are discussed in light of the coordinate expression of 4CL and other phenylpropanoid genes. PMID- 8220482 TI - Growth-related gene expression in Nicotiana tabacum mesophyll protoplasts. AB - Eight cDNAs whose genes are more strongly expressed in suspension cells in growth phase than in stationary phase and at a low level in mature leaves have been isolated. The corresponding mRNAs are abundantly accumulated in young plant organs and in germinating seeds but are almost undetectable in mature plant tissues and dry seeds. Six of these cDNAs were characterized by comparison of nucleotide and protein sequences to the EMBL and SWISSPROT databanks. These eight growth-related genes are expressed in protoplasts isolated from Nicotiana tabacum mesophyll cells shortly after preparation (4 h). Two of them are expressed in freshly isolated protoplasts (early genes), while the other six are detected after 4 h of culture (late genes). Seven are more abundantly expressed in protoplasts than in growing plant organs while one growth-related gene is weakly expressed in protoplasts, as is the histone H4 gene. They seem to be induced in protoplasts by a synergistic effect of wounding and maceration. Sustained expression of the early genes is dependent on the presence of sucrose in the culture medium. PMID- 8220483 TI - A plant gene with homology to D-myo-inositol-3-phosphate synthase is rapidly and spatially up-regulated during an abscisic-acid-induced morphogenic response in Spirodela polyrrhiza. AB - The induction of turions (dormant vegetative buds) by the plant growth regulator abscisic acid (ABA) in the aquatic angiosperm Spirodela polyrrhiza is one of the few examples of a plant hormone triggering a morphogenic response. In order to aid our understanding of the molecular basis of this phenomenon a cDNA library has been prepared from ABA-induced S. polyrrhiza and by differential screening a number of early ABA-up-regulated genes have been isolated. This paper reports the characterization of one such cDNA (tur1) from S. polyrrhiza which codes for a protein highly homologous to yeast D-myo-inositol-3-phosphate synthase (EC.5.5.1.4), the catalyst for the first committed step in inositol biosynthesis. This is the first reported cloning of a plant gene involved in inositol production. It is shown by Northern analysis and in situ hybridization that ABA induces a rapid preferential up-regulation of this gene and that this is localized to the stolon tissue. The stolon connects the developing turion to the node of the mother frond (the meristematic region involved in the production of turions which arise as a morphogenic response to this hormone). This increase in tur1 transcript level is accompanied by a rise in the activity of D-myo-inositol 3-phosphate synthase. The possible role of inositol in ABA-induced events during turion formation is discussed. PMID- 8220484 TI - Arabidopsis mutants compromised for the control of cellular damage during pathogenesis and aging. AB - Mutants of Arabidopsis thaliana which exhibit accelerated cell death in response to pathogens were isolated and characterized to gain insight into how symptom severity and disease resistance are modulated. This paper describes mutants that fall into one of two complementation groups that were identified. A novel feature of these mutants is that they are unable to control the rate and extent of cell death after exposure to a variety of stimuli that induce senescence responses. Thus, accelerated cell death (acd1) mutants show rapid, spreading necrotic responses to both virulent and avirulent Pseudomonas syringae pv. maculicola or pv. tomato pathogens and to ethylene. In addition, they develop necrotic lesions as they age and are sensitive to mechanical stress in a developmentally controlled manner. The acd1 mutants are also susceptible to opportunistic pathogens and show decreased growth inhibition of a heterologous pathogen of bean. The signal for lesion formation is not necessarily due to pathogens or wounding since plants grown aseptically also develop necrotic lesions. The lesions formed under a variety of conditions resemble those produced during a pathogen-induced rapid cell death response (the hypersensitive response, HR). Analysis of these acd1 mutants may help to explain the molecular basis of the HR and the relationship between this response and the normal process of senescence. PMID- 8220485 TI - The nitrogen response of a barley C-hordein promoter is controlled by positive and negative regulation of the GCN4 and endosperm box. AB - The 431 bp C-hordein promoter of lambda-1-17 exhibits a specific response to amino acids and NH4NO3 in developing barley (Hordeum vulgare L.) endosperms. With the aid of particle bombardment it is shown that the GCN4 motif ATGA(C/G)TCAT is the dominating cis-acting element in this response. But synergistic interaction with the neighbouring endosperm motif TGTAAAGT within the bifactorial prolamin element and cooperation with upstream sequences including a second prolamin-like element is an absolute requirement for a strong, positive regulation by an optimal nitrogen regime. Low nitrogen levels convert the GCN4 box into a negative motif. In contrast the endosperm box on its own exerted a silencing activity, independent of nitrogen nutrition. Sequence comparisons revealed that GCN4- and endosperm-like motifs are widely distributed among plant promoters. Their putative role in nitrogen regulation is discussed. PMID- 8220486 TI - 5' distal and proximal cis-acting regulator elements are required for developmental control of a rice seed storage protein glutelin gene. AB - Using a homologous transgenic rice system it is demonstrated that 5' distal and proximal cis-acting transcriptional regulatory elements are required for developmental control of a rice seed storage protein glutelin gene. Analyses of gene expression of nine progressively truncated 5' promoter sequences in developing endosperm indicated the existence of at least one major positive element located from the -5.1 to -1.8 kb region. The functional importance of proximal elements in the context of 1.8 kb promoter was demonstrated by single substitution mutations in the TATA box (-28/-23), AACA motif (-73/-61), and protein-binding boxes I (-103/-86), II (-124/-110), III (-175/-158) and IV (-200/ 217). A simultaneous mutation of five protein-binding sites (-410/-86) essentially eliminated the activity of the 1.8 kb promoter. Although temporal control of the Gt1 gene during endosperm development was retained in plants of constructs from -5.1 kb to -155 bp, spatial control of the glutelin gene was altered when the 5.1 kb promoter was deleted to -507 bp or -154 bp as the reporter gene activities of these constructs were detected in phloem of leaves, and in stems, sheaths and roots of plants. PMID- 8220487 TI - Expression of an Arabidopsis sucrose synthase gene indicates a role in metabolization of sucrose both during phloem loading and in sink organs. AB - Sucrose synthase, an important enzyme in carbohydrate metabolism, catalyzes the reversible conversion of sucrose and UDP to UDP-glucose and fructose in vitro. To investigate the in vivo function of sucrose synthase, both the gene (Asus1) and a corresponding cDNA from roots of Arabidopsis were isolated. The Asus1 gene has homologies of 67-72% to sucrose synthase genes from other species. Histochemical GUS analysis of Arabidopsis and tobacco plants transformed with a 1.5 kb Asus1 promoter fragment transcriptionally fused to the beta-glucuronidase reporter gene showed that the Asus1 gene is expressed in the phloem of leaves, and in roots. Induction is found under conditions of limited ATP supply and increased demand for translocation of carbohydrates such as anaerobic or cold treatment. During anaerobiosis the increase in RNA level leads to increased sucrose synthase activity in roots. The expression pattern and regulation of the gene suggest that sucrose synthase is involved in the supply of energy for phloem loading in source tissues, and in metabolization of sucrose in sink tissues after unloading. PMID- 8220488 TI - Myb genes from Hordeum vulgare: tissue-specific expression of chimeric Myb promoter/Gus genes in transgenic tobacco. AB - The structures of the three Myb-related genes Hv1, Hv5 and Hv33 from barley were determined. They contain a single intron located in the second repeat unit of the Myb-related domain. By analogy to the animal MYB oncoproteins this conserved region of the gene product was shown by filter-binding experiments to exhibit nucleic acid-binding activity. Tobacco plants transgenic for chimeric Myb promoter/Gus genes express the enzyme in a developmentally controlled and tissue specific manner. During germination and early stages of plant growth, GUS activity is seen in the root cap and adjacent meristematic tissue. At later stages of plant development, GUS activity is predominantly observed in the shoot apical meristem, the roots and the nodal regions of the stem. Within the stem at stages of secondary growth, Myb promoters are active in defined cell types. In the internode low GUS activity is displayed by the innermost cell layer of the cortex, the starch sheath, that surrounds the vascular cylinder of secondary xylem and phloem tissue, as well as in pith rays originating from vascular cambium initials. In the nodal region Myb promoter-controlled Gus expression is mainly confined to the abaxial starch sheath of the leaf trace, to the branch traces and to internal strands of primary phloem. It is suggested that in addition to their activity in meristematically active plant tissues Myb genes are expressed in conductive tissues that are closely associated with vascular bundles. PMID- 8220489 TI - Does the ocs-element occur as a functional component of the promoters of plant genes? AB - The structural requirements of the ocs-element, a promoter element in several genes transferred to the host plant nucleus by Agrobacterium tumefaciens and certain DNA viruses, have been further characterized both in vitro and in vivo. Two adjacent and functionally identical protein-binding sites separated by an exact number of nucleotides are required for in vivo activity of the ocs-element. Plant pathogens have presumably recruited cellular transcription factors that interact with these binding sites to drive the high-level expression of their essential genes. Our functional analyses of the ocs-elements from two pathogen promoters define the structure of a sequence motif that might also be expected to occur in plant nuclear genes, and a search of the plant gene database has identified a number of plant gene promoters that contain sequences that resemble the ocs-element. These sequences were analysed for their ability both to bind the maize nuclear protein OCSTF and to activate transcription of an inactive promoter. A functional ocs-element was identified in only one of the plant genes, the soybean heat-shock gene, Gmhsp26-A. The apparent rarity of the ocs-element in plant genes contrasts with its frequent use by pathogens that transform the plant nucleus. Sequences resembling half of an ocs-element, on the other hand, are common in plant promoters and may form part of multi-element control motifs with a variety of regulatory functions. Plant pathogens may, therefore, have evolved to circumvent tight regulatory control of their promoters by the host by duplicating the half ocs-element promoter motifs to take advantage of the ubiquitous ocs-element-binding transcription factors in plants. PMID- 8220490 TI - Constitutive and cell-division-inducible protein-DNA interactions in two maize histone gene promoters. AB - Protein-DNA interactions in the promoter regions of two maize histone genes have been analyzed by DNase I and DMS in vivo footprinting combined with LMPCR amplification. Both promoters present a bimodular structure characterized by a proximal cell division-specific set of interactions and a distal region which displays constitutive footprints but enhancement of these footprints upon cell proliferation. The inducible region contains two cis-elements common to all replication-dependent plant histone genes, one of them having previously been shown to be a target for the wheat nuclear protein HBP-2. In the constitutive region, the first demonstration for the existence of a transcription factor binding to the highly conserved plant histone-specific octamer CGCGGATC is provided. Exchange of cell-type-specific factors is postulated to occur at that site. Additional immediate upstream constitutive elements binding regulatory proteins include a degenerate octameric sequence, a CCAAT-box, a CACCC sequence and composite ACGTCA/ACGTGG hexameric sequences binding HBP-1-related trans acting factors. The close proximity of these elements within the constitutive region and the redundancy of some of them suggest complex cooperation and competition mechanisms contributing to achieve the final expression level and likely also to mediate the interplay between constitutive and inducible factors. PMID- 8220491 TI - Pathogen, salicylic acid and developmental dependent expression of a beta-1,3 glucanase/GUS gene fusion in transgenic tobacco plants. AB - The 5' flanking region of a gene encoding an acidic beta-1,3-glucanase from Nicotiana tabacum was isolated and characterized. A chimeric gene composed of 1759 bp of the promoter sequence from the PR-2 gene was fused to the beta glucuronidase (GUS) coding region and used to transform tobacco. Transcriptional activation of the PR-2 promoter was investigated in response to inoculation with tobacco mosaic virus (TMV), after treatment of leaves with salicylic acid (SA), and in specific tissues during the normal development of healthy plants. In TMV inoculated transgenic plants, GUS activity was induced locally around necrotic viral lesions and systemically in uninoculated leaves. GUS activity was also induced by treatment of leaves with SA. The chimeric gene was expressed in floral organs of healthy plants and in newly germinated seedlings. Analyses of a series of 5' deletions of the glucanase promoter indicated that the cis-acting elements necessary for induction by all these signals are localized in the region between 321 bp and -607 bp upstream of the transcription start site. PMID- 8220492 TI - Tissue-specific and wound-inducible pattern of expression of the mannopine synthase promoter is determined by the interaction between positive and negative cis-regulatory elements. AB - In transgenic tobacco plants the regulatory region of the Agrobacterium genes involved in mannopine synthesis (pmas) directs expression in vascular tissues and is induced upon wounding. To identify cis-acting sequences required for the cell type-specific and wound-inducible expression of this regulatory region, the expression pattern of chimeric genes in which 5' upstream deletions of the pmas 1' promoter direct the expression of the beta-glucuronidase coding sequence, was analyzed in transgenic tobacco plants. It was found that the pmas1' promoter is specifically expressed in phloem cells and that this tissue-specific pattern of expression is the result of the interaction of at least two negative regulatory elements with a positive element that directs expression in many cell types. It was also found that wound induction is mediated by two different mechanisms, one of them involving a dramatic change in tissue-specific expression. PMID- 8220493 TI - Activation of a tobacco glycine-rich protein gene by a fungal glucan preparation. AB - A Phytophthora megasperma f.sp. glycinea cell wall glucan preparation was previously shown to protect tobacco plants against viral infection. Eleven plant defense-related genes were assayed for elevated mRNA accumulation levels in response to glucan treatment of tobacco plants. The expression of only one of these genes, a glycine-rich protein (GRP) gene, was induced by glucan application. Elevated GRP gene mRNA levels could be detected within 15 min of glucan treatment and reached maximum levels at 4 h post-treatment followed by a slow decline to 8 h. The maximum induction of the GRP gene was approximately ninefold above H2O-treated control plants. Northern blot analysis showed that a single mRNA species of 1.4 kb was responding to the glucan treatment. GRP genes occur in tobacco as members of a multigene family, but only one specific GRP gene was induced by the glucan treatment. A genomic copy of this responding GRP gene was cloned and sequenced. This tobacco GRP gene is homologous to the petunia ptGRP1 gene and the French bean GRP1.8-gene, but is not closely related to the French bean GRP1.0 gene. GRP gene expression has previously been associated with disease resistance in plants, but it remains to be determined whether beta-glucan activation of the tobacco GRP gene results in the observed resistance to virus. PMID- 8220494 TI - Interaction between the tobacco DNA-binding activity CBF and the cyt-1 promoter element of the Agrobacterium tumefaciens T-DNA gene T-CYT correlates with cyt-1 directed gene expression in multiple tobacco tissue types. AB - A novel DNA-binding activity, designated CBF, has been identified in nuclear extracts from tobacco leaf, stem and root tissue. CBF interacts specifically with a 30 bp promoter fragment, referred to as cyt-1, of the Agrobacterium tumefaciens T-DNA cytokinin (T-cyt) gene. The T-cyt promoter, although of bacterial origin is active in planta and the 30 bp cyt-1 element is located within a region that is essential for T-cyt promotor activity in leaf, stem and root cells of tobacco plants. Gel retardation assays using different synthetic oligonucleotides and methylation interference experiments pinpointed the binding site of CBF to a GC rich sequence ATGCCCCACA within the cyt-1 element. Site-directed mutagenesis of the CBF binding site within the T-cyt promoter by using PCR resulted in an almost complete loss of T-cyt promoter activity in transgenic tobacco plants. In a gain of-function experiment a hexamer of cyt-1 was shown to be able to confer leaf, stem and root expression when fused upstream of a TATA box containing -55 derivative of the T-cyt promoter. A mutant cyt-1 hexamer, defective in CBF binding, did not show activity above background levels. These results indicate that binding of CBF to the cyt-1 element is required for cyt-1 directed gene expression, suggesting that CBF might act as a transcriptional activator. Apart from the ASF-1 binding site of the CaMV 35S promoter, which is also present in the T-DNA nopaline and octopine synthase genes, the cyt-1 element is the only other identified element reported until now that in combination with a TATA box is sufficient to drive gene expression in multiple tobacco tissue types. PMID- 8220495 TI - Molecular characterization of the gene for carrot cell wall beta-fructosidase. AB - Carrot cell wall beta-fructosidase, previously purified and cloned, is encoded by a single, wound- and pathogen-inducible gene. The developmental regulation of the gene was studied by determining the steady-state mRNA levels in different organs during carrot development: cell wall beta-fructosidase mRNA was detected in roots and leaves of young plants but not during tap root development. A genomic clone was isolated and characterized. The transcription start site was determined by primer extension analysis. Inspection of the promoter sequence (1488 bp) revealed the presence of sequences with high homology to cis-acting elements for the regulation of plant genes by wounding and infection. The 5'-regulatory sequence was fused to the reporter gene beta-glucuronidase (GUS) and tested in a transient expression assay with carrot suspension cells and wounded carrot root tissue (aged disks of carrot roots). The expression of the GUS gene in the transfected cells proved that the isolated promoter was functional. In transgenic tobacco plants containing the cell wall beta-fructosidase promoter fused to GUS, the reporter gene was predominantly expressed in the shoot and root meristems of young seedlings. No GUS expression was detected in mature tobacco plants, showing that the development-specific regulation of the cell wall beta-fructosidase promoter seen in carrot was maintained in tobacco plants. In contrast, expression of the GUS reporter gene in transgenic tobacco was not wound inducible. To analyze the functional organization of the cell wall beta-fructosidase promoter, a 5'-deletion series was generated and tested in a transient expression assay in protoplasts of Nicotiana plumbaginifolia. Two regions containing putative silencer elements were identified. A comparison of these regions with known silencer elements identified in both regions one copy of the negative dominant cis-acting element found in a chalcone synthase promoter of petunia. PMID- 8220496 TI - Site-directed mutagenesis of the organ-specific element in the soybean leghemoglobin lbc3 gene promoter. AB - The expression of a soybean leghemoglobin 5'lbc3-GUS-3'nos chimeric gene was analyzed in Lotus corniculatus after site-specific mutagenesis of the nodulin consensus sequences, AAAGAT and CTCTT, present in the organ-specific element (OSE) (-139 to -102). Full-length promoters (-1956, +46) carrying clustered point mutations in the CTCTT sequence or in both the AAAGAT and the CTCTT sequences were inactive. Point mutations in the AAAGAT sequence had only minor effects on the expression level. Substitution of the ATTG sequence between the AAAGAT and the CTCTT sequences in the OSE reduced the activity in nodules to 10%. This, together with the conservation of the ATTGT sequence in the same position of leghemoglobin genes from other legumes, indicates that these sequences, in addition to the nodulin consensus sequences of the OSE, are important for high level nodule-specific expression. Substitution of the CTCTT sequences outside the OSE (-44, -40 and -79, -75) results in promoter activities of approximately 50%. PMID- 8220497 TI - Effect of 2 inhibitors of oxidative phosphorylation on urea excretion in rats. AB - The effects of phloretin and carbonyl-cyanide-m-chlorophenylhydrazone (CCCP), both inhibitors of oxidative phosphorylation, on renal urea excretion in Wistar rats were investigated. Phloretin and CCCP infusions did not influence plasma urea concentration (P(urea)), compared with controls (0.15 M NaCl and Tris solution in 0.15 M NaCl-a solvent for phloretin and CCCP). The fractional urea excretion (FEurea) was not altered by phloretin infusion. It decreased significantly only when compared with 0.15 M NaCl infusion (P < 0.05). CCCP infusion had no effect on FEurea. The total amount of urea excreted by urine (UureaV) was not altered by phloretin compared with controls. CCCP significantly enhanced Uurea V only when compared with 0.15 M NaCl (P < 0.001), not when compared with Tris. Glomerular Filtration rate (GFR) increased significantly during phloretin infusion (P < 0.001), CCCP (P < 0.001) and also after Tris in 0.15 M NaCl (P < 0.001), in comparison with 0.15 M NaCl alone. Our results showed that phloretin and CCCP had no effect on urea excretion in rats. The increase in GFR is attributed to Tris, not to phloretin or CCCP. It is concluded that inhibition of oxidative phosphorylation in kidney has no effect on urea excretion. PMID- 8220498 TI - Escherichia coli producing CNF1 and CNF2 cytotoxins in animals with different disorders. AB - Two DNA probes were used for the detection of CNF1- and CNF2-positive E coli strains in a collection of 553 E coli isolates from cattle, sheep, goats, pigs, horses, dogs, cats and poultry. CNF-positive E coli were frequently associated with septicaemia in cattle, dogs, and cats, with diarrhoea in calves, cats and dogs, and with abortion in bovine and porcine species. CNF2-positive strains were observed among adult healthy cattle. They were also found in cases of pneumonia, metritis, mastitis in cattle and in 1 case of metritis of a mare. The physiopathology induced by CNF-positive E coli strains remains to be elucidated. However, the impact of CNF strains on veterinary pathology is clear and the diagnosis of CNF-producing E coli should become routine in veterinary practice. PMID- 8220499 TI - [Antibacterial sulfonamides, antiparasitic and antifungal derivatives of imidazole: evaluation of their antithyroid effects in the rat]. AB - Antithyroid action of some antibacterial, antiparasitic or antifungal agents, was studied by 2 in vitro and 3 in vivo experimentations in the rat. These drugs can upset thyroid hormone synthesis by forming a molecular complex with iodine, and/or by inhibiting thyroid peroxidase activity. Rats treated with these drugs showed an hypothyroidism, demonstrated both by a decrease in T4 concentration and an hyperactivity of thyroid gland by positive feed-back, whose consequence was the presence of cylindrical cells. We noticed this iatrogenic hypothyroidism with all the drugs experimented, by an increase in thyroid gland weight. But the increase of rats body weight, which should have appeared, was not shown. The use of anabolic steroid is now forbidden, therefore, such drugs could be used for breeding animals, in order to gain body weight. Detection of use of these drugs in breeding, to obtain this side effect, should be advised. PMID- 8220500 TI - Irrigation, faecal water content and development rate of free-living stages of sheep trichostrongyles. AB - The effect of irrigation by flooding the pastures on the ability of the eggs of sheep Trichostrongyles to develop into infective larvae (L3) was estimated in outdoor conditions by depositing parasitised faeces on plots, without irrigation or submerged, at different times and durations. The rates of development of Teladorsagia circumcincta, Trichostrongylus vitrinus and Chabertia ovina were very low in spring and summer in dry plots but proportional to the duration of submersion in the irrigated plots. T circumcincta was mainly favoured in spring, T vitrinus in summer, but higher rates were observed in autumn. The action of water had more effect on freshly deposited faeces. In laboratory experiments on T circumcincta, T vitrinus and Haemonchus contortus, the submersion of cultures was unfavourable to egg development but favoured L1 development. Cultures with different faecal water contents (FWC) simulating a submersion (7 or 16 h) or an alteration of spraying and dehydration, or at constant values of 60 and 50% enabled us to conclude that high FWC favoured the development of T vitrinus, had some negative effect on T circumcincta, but H contortus was more susceptible to variations of FWC. The FWC had an effect on the size of L3 and, for T circumcincta only, the survival rate of the small L3 obtained at low FWC seemed decreased. These data could explain the absence of H contortus, as well as the abundance of T vitrinus on the studied pastures. PMID- 8220501 TI - [The reason for the preclinical diagnosis of insulin-dependent or type I diabetes mellitus]. PMID- 8220502 TI - [Pyogenic liver abscesses: analysis of 36 cases treated by percutaneous drainage]. AB - Thirty-six patients with pyogenic liver abscess treated by percutaneous drainage plus antibiotic therapy were reviewed. The most frequent symptoms were fever (75%) and pain (72.2%), and the most common physical signs were liver enlargement (58.3%) and jaundice (33.3%). The mean time interval from admission to diagnosis was 16 days. CT scans and ultrasonography were diagnostic in 100% of the patients. The percutaneous drainage was effective in one attempt in 19 patients, two attempts in 8, three attempts in 8 patients and more than four attempts in only one patient. There were three patients with hemoperitoneum (8.7%) as a post drainage complication, one of them needed to be treated surgically. Mean hospital stay was of 24.8 days and the mortality rate was 5.5%. Percutaneous drainage plus antibiotic therapy is then an efficient therapeutic approach to the treatment of pyogenic liver abscess. PMID- 8220503 TI - [Locally advanced cancer of the breast (LACB) and identification of estrogen receptors with monoclonal antibodies]. AB - The effects of therapy in locally advanced breast cancer submitted to combined conventional telecobalt therapy plus chemotherapy with cyclophosphamide and 5 fluorouracil were studied in 49 patients. Associated to radical mastectomy in operable cases. Local tumor control was achieved in 86.7%. There were no local recurrences in those submitted to surgery but they reached 21.7% in inoperable patients who received only radiation therapy and chemotherapy. The median follow up time for dead patients was 29.5 months and for living patients 79.3 months. The index of complete responses was 24.5% and the median disease free interval was 22.9 months. The overall survival rate, between three and five years, was 32.7%. Estrogen receptors were identified by using immunohistochemical assay ER ICA and monoclonal antibody H222-SP gamma, Abbott. There were no differences in the complete response index, disease free interval and survival rates, among ER positive and ER-negative patients, explained by the far advanced stage of the disease. ER-positivity was significantly correlated with histological features of the tumors: cell differentiation, presence of elastosis, absence of lymphocytic infiltration and absence of tumor necrosis. PMID- 8220504 TI - [The influence of socio-economic conditions in renal posttransplant infection]. AB - Two hundred and four patients who underwent renal transplantation were followed up as outpatients with a minimum of four years. They were divided into two socio economic levels: group I - 104 patients who underwent transplantation in a private hospital and 120 patients (group II) with a lower socio-economic standard, treated in a public hospital. In both groups urinary infections and hepatitis were excluded. The incidence of infection in group I was 24% and in group II, 50% (p = 0.0002). There was no difference in relation to viral infection in either groups. However, bacterial infection and infection by opportunistic agents were significantly higher in group II (p = 0.0001 and p = 0.0282). The number of hospitalizations and the number of infections of patients were higher in group II. There was a tendency for an increase in mortality owing to infection in group II. There was no difference in the two groups as the parameters of: age, sex, type of donor, primary disease, number of rejections crises, level of serum creatinine and number of patients with ciclosporine. On the other hand, the dose of azathioprine and prednisone was mildly higher in those patients of group II. Low level of socio-economic conditions is a risk factor in renal transplant patients. PMID- 8220505 TI - [Clinical characteristics and prognostic implications of renal involvement in multiple myeloma]. AB - The renal involvement in patients with multiple myeloma has been described as a sign of poor prognosis. The influence of renal insufficiency in the clinical patterns and in the prognosis of patients with multiple myeloma was studied retrospectively in 45 patients. Patients with renal insufficiency, at first visit, more often presented weight loss, proteinuria, hypercalcemia. The means of uricemia, ESR, were higher and the hematocritic mean was lower in patients with renal insufficiency. There was no difference in edema, arterial hypertension, fractures and bone pain. The reversibility of renal insufficiency occurred in 47% of the cases, which happened more often in the first months of the follow up. The creatinine mean was lower in patients with reversible renal insufficiency. The median survival was: patients with renal insufficiency: 11 months; patients with normal renal function: 50 months. Among patients with renal insufficiency those with recuperation of renal function showed a higher median survival (24 months) than those with irreversible renal insufficiency (1 month). The renal involvement then is frequent and often reversible. Patients with impaired renal function showed a worse prognosis; normalization of the renal function was associated with a better outcome. PMID- 8220506 TI - [Snake bites in the state of Sao Paulo, Brazil]. AB - From 1986 to 1989, 8,721 accidents caused by poisonous snakes have been notified to the Government of the State of Sao Paulo (Brazil), Health Department, which represented the average annual incidence rate of 6.8 to 7.4/100,000 persons. The classification of the snake genus had been possible in 6,834 cases and the distribution was: Bothrops (85.6%), Crotalus (13.3%) and Micrurus (1.1%). The vast majority of cases (5,807) occurred from November to April. The age distribution shows that 74.4% of the accidents had been suffered by people from 10 to 49 year old people with great predominance in males (77.0%). The anatomical areas more frequently bitten were feet and ankles (52.8%), hands (20.5%) and legs (17.2%). At the health center 67.5% of the patients had been treated within the first, second and third sixth hour after the accident. The distribution according to the severity of poisoning was: light (53.5%), moderate (38.3%) and severe (8.2%). The case fatality rate was 0.4%, 60,954 vials of various anti-venoms were used (an average of 7.0 vials per patient). Accidents owing to poisonous snakes are frequent in the State of Sao Paulo; the most important genus is Bothrops; the young male population is more often attacked; they are an important cause of death. PMID- 8220507 TI - [Hydroelectrolyte, acid-base, and renal function changes in patients with acquired immunodeficiency syndrome]. AB - BACKGROUND: A variety of metabolic and renal disturbances have been described in patients with Acquired Immunodeficiency Syndrome (AIDS) but their influence on the clinical outcome has not been reported. The present study was undertaken in order to evaluate the prevalence of fluid and electrolyte, acid-base, and renal function disturbances in AIDS patients. The influence of these abnormalities on the clinical outcome was studied as well. MATERIAL AND METHODS: Following to a previously established protocol, the charts of all patients hospitalized during the first semester of 1989 were reviewed. RESULTS: The prevalence of hyponatremia was 45% and 80.7% at admission and during hospitalization respectively of 99 patients. Hypokalemia was present in 23.1% of the patients. Metabolic acidosis and renal failure were 20.1% and 28.4% prevalent. The relative risk for mortality in patients with hypokalemia was 4.4. Metabolic acidosis and acute renal failure had relative risks of 12.9 and 21.4. CONCLUSIONS: There is an elevated prevalence of fluid and electrolyte, acid-base and renal function disturbances in these patients. The presence of hypokalemia, metabolic acidosis, and renal failure are significantly associated with mortality in AIDS. PMID- 8220508 TI - [The non-insulin-dependent phase of type I diabetes mellitus]. AB - Case report on a child whose type I diabetes mellitus was diagnosed 23 months before the appearance of overt glucose intolerance. In this pre-IDDM stage of DMI were observed secondary enuresis, decreased growth speed, transient hyperglycemia and asymptomatic glycosuria. These alterations may represent the earliest clinical manifestation of impaired beta cell function. Immunologic markers (ICA and/or AAI) of DMI and abnormalities of the first-phase insulin secretion in response to intravenous glucose also may precede by several months the most common clinical picture of type I diabetes as they were detected in this child. If possible, markers and alterations should be tested in such patients and their young relatives with DMI in order to detect high risk individuals who may develop DMI. Such and accurate predictive ability should be a prerequisite to institution of appropriate therapy to preventing further beta cell destruction and severe metabolic decompensation, thus having the potential to reduce morbidity and mortality from new onset DMI. PMID- 8220510 TI - [Surgical clothes dressing. The most adequate time to put on gloves in relation to tying the wrapping apron coat]. PMID- 8220509 TI - [Treatment of acute diarrhea: updating concepts and undoing prejudices]. PMID- 8220511 TI - [Artificial prolongation of life: when and how]. PMID- 8220512 TI - [Hormonal treatment of postmenopausal Xikrin indians]. PMID- 8220513 TI - [Initial experience with the AKA-2 and AKA-4 device for intestinal compression anastomosis in colorectal surgery]. AB - A prospective study was undertaken to analyse the results of sutureless colorectal anastomosis, by using an anastomotic compression device designed by Russians, the AKA gun. Ten patients were submitted do colorectal resection, 5 for retrosigmoid cancer, 3 for familial adenomatous polyposis and 2 for rectal procidentia. No mortality. Anastomotic leakage occurred in 1 patient which was treated by a defunctioning colostomy and had a good recovery. Clinical, radiologic and endoscopic postoperative controls were within normality. Comparisons are made between the sutureless anastomosis technique and the traditional ones. Initial results are regarded, by the authors, as encouraging and so they intend to go on the study. PMID- 8220514 TI - The technical and political dimensions of health. PMID- 8220515 TI - Maternal mortality in Latin American urban areas: the case of Sao Paulo, Brazil. AB - This article describes maternal mortality trends in Sao Paulo, Brazil, from 1960 through 1990. In so doing, it compares mortality rates derived from death certificate data with rates suggested by three independent surveys conducted in the city of Sao Paulo in 1962-1963, 1974-1975, and 1986. In general, these data indicate that a substantial share of all maternal deaths in the city have been ascribed to other causes on death certificates, that prevailing maternal mortality levels are far higher than those found in the urban areas of most developed countries, and that in recent years levels of maternal mortality in the city have been rising. Various measures are suggested for improving the accuracy of available data and reducing the maternal mortality they describe. PMID- 8220516 TI - Stabilization ponds in the tropics: promotion of the sanitary reuse of water. AB - This article reports the results of efforts by PAHO's Environmental Health Program to lay the groundwork for designing wastewater stabilization ponds suited to tropical areas. The resulting design concepts are flexible (permitting pond construction to be adapted to a broad range of terrains, community sizes, and working temperatures) and directed at meeting WHO standards established for the microbial quality of effluents used in agriculture and aquaculture. The WHO standards (1) call for treated wastewater being used in agriculture or aquaculture to contain less than 1,000 fecal coliforms per 100 ml. The plans outlined here, which are calculated to meet those standards, seek to minimize the pond area and volume needed by using two high-load primary anaerobic ponds discharging into an elongated secondary pond with a length-to-width ratio of at least 15:1. In rough terrain the elongated pond can be allowed to meander, following the land's natural contours. However, where the terrain is level it is recommended that a system of partitions be used to maintain the 15:1 ratio for operating purposes while changing the actual ratio of the secondary pond's outer dimensions to something like 5:3. Basic equations presented in the text will be helpful in estimating the pond sizes needed to cope with different climatic conditions, community sizes, per capita rates of wastewater generation, and per capita biochemical oxygen demands. While these equations should prove of great assistance during initial planning and development of preliminary criteria, nothing in this article supplants the topographic and geotechnologic studies that will be needed in order to clearly determine what is feasible in any given case. PMID- 8220517 TI - National laboratory surveillance of viral agents of gastroenteritis in Brazil. AB - In 1984 an enzyme immunoassay for rotavirus and adenovirus developed in the Virology Department of the Oswaldo Cruz Foundation was distributed to laboratories in 14 Brazilian states as part of a project to survey viral agents in fecal specimens from children with diarrhea. The ensuing surveillance continued for 3 to 5 years, and in 1991 the results obtained by all laboratories that tested 300 or more fecal specimens were reviewed at a workshop held in Belem. These results showed that rotavirus had been detected in 13% to 20% of the specimens tested, with positive specimens appearing to peak in the May to September "winter" or dry season in Brazil's central and southern states but not in the more tropical northern areas. Adenovirus, detected in 0.7% to 5.5% of the specimens tested for it, showed no seasonal variations. Many other viral agents known to cause gastroenteritis (e.g., astrovirus, small round-structured viruses, calcivirus, and group C rotavirus) were detected at centers that used electron microscopy. Picobirnavirus, a novel agent not yet associated with gastroenteritis in humans, was found by polyacrylamide gel electrophoresis in specimens from a number of centers using this technique. Vaccines to prevent rotavirus that are currently under development would be of great use in Brazil, where rotavirus is the most common cause of childhood diarrhea. Improved diagnostics will be required to assess the importance of the other viral agents. PMID- 8220518 TI - AIDS-related knowledge, attitudes, beliefs, and practices in Haiti. AB - AIDS constitutes an important public health problem in Haiti, where it appears to be spread mainly through heterosexual encounters. The study reported here employed in-depth interviews, focus group discussions, and a national cross sectional survey of 1,300 men and 1,300 women 15 to 49 years old to assess AIDS related knowledge, attitudes, beliefs, and practices in Haiti. According to criteria established for the study, 38.1% of the 1,118 sexually active male survey respondents were found to engage in high-risk behavior. In general, the women were found to have better knowledge of AIDS than the men. Significant obstacles to condom use included the inability of women to choose whether condoms would be used and a belief that condom lubricant could cause health problems. The study also found a tendency to ostracize people with AIDS, especially in areas outside Port-au-Prince, and a belief that AIDS was imposed on people by fate- which could partially explain the tendency to persist in high-risk behavior. PMID- 8220519 TI - Gastroenteritis epidemic in the area of the Itaparica Dam, Bahia, Brazil. AB - Dam construction and associated flooding along rivers can alter ecosystems and pose serious threats to the welfare and health of local populations. This article describes a severe gastroenteritis epidemic in the Paulo Afonso region of Brazil's Bahia State related to flooding of the newly constructed Itaparica Dam's reservoir in 1988. Some 2,000 gastroenteritis cases, 88 of which resulted in death, were reported over a 42-day period. Responding to the outbreak, clinical data and water sample test results were reviewed; blood and fecal specimens from gastroenteritis patients were subjected to bacteriologic, virologic, and toxicologic testing; and drinking water samples were examined for microorganisms and heavy metals. The results revealed that the source of the outbreak was water impounded by the dam and pointed to toxin produced by cyanobacteria as the responsible agent. Proliferation of these microbes, present at concentrations of 1,104 to 9,755 standard cyanobacterial units per milliliter in untreated water, appears to have been encouraged by the decomposing biomass and other conditions prevailing in the newly flooded reservoir area.